Metabolism

Cholic Acid-Derived Gemini Amphiphile Can Eradicate Interkingdom Polymicrobial Biofilms and Wound Infections

125 | Feb 16 2024

The bile acid-derived gemini amphiphile G21 exhibits broad-spectrum antimicrobial efficacy, disrupting microbial cell membranes and eradicating polymicrobial biofilms while curbing drug resistance, indicating its potential as a versatile agent for combatting chronic infections. [Read the Full Post]

Sensitive fluorescence ELISA for the detection of zearalenone based on self-assembly DNA nanocomposites and copper nanoclusters

155 | Feb 05 2024

An enzyme nanocomposite-based fluorescence ELISA method was developed, exhibiting a significantly lower limit of detection (0.26 ng mL-1) for Zearalenone in food samples compared to traditional ELISA, with high accuracy, selectivity, and potential for enhancing trace detection in ensuring food safety. [Read the Full Post]

Alcohol induces neural tube defects by reducing retinoic acid signaling and promoting neural plate expansion

137 | Feb 03 2024

Reduced retinoic acid signaling, induced by inhibitors or ethanol exposure, disrupts early neuroectodermal network regulation, increasing neural precursor proliferation and expanding the neural plate, thereby leading to the induction of neural tube defects during embryogenesis. [Read the Full Post]

An update on emerging drugs for the treatment of idiopathic pulmonary fibrosis: a look towards 2023 and beyond

135 | Jan 30 2024

Advances in IPF research are driving an exponential surge in clinical trials testing novel treatments, aiming not only to stabilize but potentially reverse the fibrotic process, signaling a promising shift toward expanded therapeutic options and improved patient outcomes. [Read the Full Post]

vPIF-1 is an insulin-like antiferroptotic viral peptide

146 | Jan 28 2024

The study reveals how viral insulin-like peptides, exemplified by LCDV-1 VILP, serve as potent inhibitors of ferroptosis, highlighting their specificity in preventing this form of cell death and suggesting a potential viral defense mechanism in lower organisms. [Read the Full Post]

Temporal landscape of mitochondrial proteostasis governed by the UPRmt

106 | Jan 28 2024

The study elucidates the intricate network of mitochondrial proteostasis controlled by the unfolded protein response (UPRmt), showcasing its pivotal role in safeguarding and repairing damaged mitochondrial proteins, particularly emphasizing its impact on oxidative phosphorylation metabolism and its interplay with PINK1/Parkin-mediated mitophagy for cellular recovery during stress. [Read the Full Post]

Identification of GDC-1971 (RLY-1971), a SHP2 Inhibitor Designed for the Treatment of Solid Tumors

143 | Jan 27 2024

The clinical trials combining GDC-1971, a SHP2 inhibitor, with divarasib (GDC-6036), a KRAS G12C inhibitor, represent a promising strategy for targeting RAS-driven MAPK signaling in solid tumors harboring KRAS G12C mutations. [Read the Full Post]

The relationship between discrimination, alcohol use severity, and PTSD symptoms among Latinx heavy drinkers

129 | Jan 27 2024

This study underscores how discrimination's impact on alcohol use severity among Latinx adults is intricately connected to PTSD symptoms, highlighting the need for culturally adapted interventions tailored to those with higher PTSD symptomatology. [Read the Full Post]

First-in-Class NADH/Ubiquinone Oxidoreductase Core Subunit S7 (NDUFS7) Antago

225 | Jan 26 2024

Inhibiting oxidative phosphorylation via the NDUFS7 antagonist DX2-201 presents a promising and novel therapeutic strategy for pancreatic cancer, demonstrating efficacy, direct targeting of drug resistance mechanisms, and synergistic potential with metabolic and PARP inhibitors. [Read the Full Post]

The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity

136 | Jan 22 2024

The discovery of ABBV-CLS-484 (AC484), a first-in-class active-site inhibitor of PTPN2 and PTPN1, showcases a promising new direction in cancer immunotherapy by enhancing immune response and generating potent anti-tumour effects in preclinical models, offering hope for overcoming resistance to existing treatments. [Read the Full Post]

Synthesis and structure-activity relationship of new nicotinamide phosphoribosyltransferase inhibitors with antitumor activity on solid and haematological cancer

193 | Jan 21 2024

The synthesized compounds, particularly 35a, 39a, and 47, exhibit potent nanomolar/sub-nanomolar cytotoxicity against a range of cancer cell lines, showcasing promising anti-cancer potential via NAMPT inhibition and subsequent disruption of the NAD+ pathway, leading to cell death. [Read the Full Post]

A pro-death autophagy-based nanoplatform for enhancing antitumour efficacy with improved immune responses

99 | Jan 20 2024

The innovative CS-3BP/PA@DOX nanoplatform demonstrates promising potential by leveraging pro-death autophagy, immune modulation, and chemotherapeutic strategies to comprehensively target the tumor microenvironment and enhance anti-tumor efficacy while offering a new therapeutic direction through 3-bromopyruvic acid (3BP) in cancer treatment. [Read the Full Post]

PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy

175 | Jan 20 2024

The study highlights protocadherin 1 (PCDH1) as a pivotal prognostic biomarker and metastasis promoter in pancreatic adenocarcinoma (PAAD), suggesting flutamide's potential as a therapeutic avenue by down-regulating PCDH1 expression to impede PAAD progression. [Read the Full Post]

Physicochemical investigation and molecular docking analysis of Maha yogaraj Guggulu tablet and virtual screening of its major bioactive compound

101 | Jan 17 2024

A computational study identified Guggulsterone isomers as potential high-affinity inhibitors of the Farnesoid X Receptor with promising cholesterol-lowering capabilities, while indicating concerns regarding their CYP3A4 inhibition and hepatotoxicity. [Read the Full Post]

Inhibition of thioredoxin-1 enhances the toxicity of glycolysis inhibitor 2-deoxyglucose by downregulating SLC1A5 expression in colorectal cancer cells

187 | Jan 17 2024

The study reveals that Trx-1 mediates resistance to 2-deoxyglucose in colorectal cancer cells by upregulating SLC1A5, suggesting that targeting Trx-1 or SLC1A5 alongside glycolysis inhibition could offer a promising strategy for improving treatment efficacy. [Read the Full Post]

GW0742 reduces mast cells degranulation and attenuates neurological impairments via PPARβ/δ/CD300a/SHP1 pathway after GMH in neonatal rats

165 | Jan 13 2024

The study presents compelling evidence that GW0742, a PPARβ/δ agonist, attenuates mast cell-induced inflammation post-germinal matrix hemorrhage (GMH) by activating the CD300a/SHP1 pathway, offering a promising avenue for mitigating brain injury in GMH patients. [Read the Full Post]

Network pharmacology integrated with molecular docking technology to reveal the potential mechanism of Shuganfang against drug-induced liver injury

117 | Jan 12 2024

The comprehensive study on Shuganfang's mechanism in treating drug-induced liver injury through network pharmacology and molecular docking revealed multiple active ingredients, core targets, and pathways, establishing a solid foundation for its potential as a therapeutic option. [Read the Full Post]

Validation of a highly sensitive HaloTag-based assay to evaluate the potency of a novel class of allosteric β-Galactosidase correctors

98 | Jan 11 2024

SEE-Tx® technology identified STAR compounds that effectively enhanced the transport and activity of β-galactosidase enzymes, showcasing promise for treating lysosomal storage disorders associated with GLB1 mutations. [Read the Full Post]

Prognosis and personalized medicine prediction by integrated whole exome and transcriptome sequencing of hepatocellular carcinoma

113 | Jan 08 2024

The comprehensive analysis of hepatocellular carcinoma mutations, particularly highlighting TP53 and LRP1B, suggests a tailored prognostic risk model for TP53 wild-type patients and identifies potential therapeutic implications, such as AM580, opening avenues for personalized treatment approaches. [Read the Full Post]

Targeting stearoyl-coa desaturase enhances radiation induced ferroptosis and immunogenic cell death in esophageal squamous cell carcinoma

125 | Jan 07 2024

Targeting Stearoyl-coa desaturase 1 (SCD1) using MF-438 induced ferroptosis, enhanced immunogenicity, and improved radiation sensitivity in esophageal squamous cell carcinoma (ESCC), offering potential therapeutic avenues and identifying SCD1 as a prognostic marker for ESCC survival. [Read the Full Post]

Pycard deficiency inhibits microRNA maturation and prevents neointima formation by promoting chaperone-mediated autophagic degradation of AGO2/argonaute 2 in adipose tissue

121 | Jan 06 2024

The study reveals that PYCARD regulates neointima formation by inhibiting chaperone-mediated autophagy-induced degradation of AGO2, impacting microRNA biogenesis independently of inflammasome activity, offering potential therapeutic strategies for vascular conditions. [Read the Full Post]

Liquid chromatography-tandem mass spectrometry based simultaneous quantification of tryptophan, serotonin and kynurenine pathway metabolites in tissues and cell culture systems

186 | Jan 05 2024

This groundbreaking UPLC-MS/MS method for quantifying kynurenine-related metabolites holds immense promise in unraveling intricate disease pathways and could pave the way for targeted therapeutic interventions. [Read the Full Post]

Serum macrophage migration inhibitory factor levels predict brain atrophy in people with primary progressive multiple sclerosis

127 | Jan 02 2024

Baseline serum MIF levels in primary progressive MS correlated with faster brain atrophy, showing a sex disparity with higher levels in males, while ibudilast treatment didn't significantly alter MIF levels. [Read the Full Post]

Rapid Formation of Intramolecular Disulfide Bridges using Light: An Efficient Method to Control the Conformation and Function of Bioactive Peptides

112 | Jan 02 2024

The light-mediated strategy utilizing 2-nitroveratryl (oNv) for controlled disulfide bond formation in peptides offers precise spatiotemporal regulation, enabling the restoration of native structures and functions, showcasing potential for targeted therapies and smart biomaterial design. [Read the Full Post]

Active Components of Leontopodium alpinum Callus Culture Extract for Blue Light Damage in Human Foreskin Fibroblasts

595 | Dec 31 2023

Research on Leontopodium alpinum callus culture extract's components, particularly leontopodic acid A, reveals promising potential in protecting skin cells from blue light damage, offering avenues for future skincare and pharmaceutical developments. [Read the Full Post]

P7C3-A20 treats traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis

123 | Dec 31 2023

"P7C3-A20 treatment post-traumatic brain injury in rats exhibited neuroprotective effects by mitigating excessive autophagy and apoptosis, as evidenced by improved neurological deficits, reduced neuronal damage, and specific alterations in key protein expressions associated with these cellular processes." [Read the Full Post]

A tool for nuclear imaging of the SARS-CoV-2 entry receptor: molecular model and preclinical development of ACE2-selective radiopeptides

180 | Dec 30 2023

This study developed gallium-labeled radiopeptides, notably [67Ga]Ga-HBED-CC-DX600, showing selective ACE2 targeting and promising tissue distribution, offering a potential noninvasive imaging tool to assess (patho)physiological ACE2 expression levels post-SARS-CoV-2 infection. [Read the Full Post]

Identification of upregulated genes in glioblastoma and glioblastoma cancer stem cells using bioinformatics analysis

385 | Dec 29 2023

This comprehensive study uncovered potential therapeutic targets for glioblastoma by identifying highly coexpressed genes in cancer stem cells, highlighting DUSP6 and SOX2 as prognostically relevant hub genes and proposing (E/Z)-BCI and BCI compounds as promising anti-cancer agents via strong binding interactions with DUSP6's ERK2 binding domain. [Read the Full Post]

Increased palmitoylation improves estrogen receptor alpha-dependent hippocampal synaptic deficits in a mouse model of synucleinopathy

117 | Dec 29 2023

The study highlights how the modulation of estrogen receptor alpha (ERα) through palmitoylation plays a pivotal role in mitigating synaptic abnormalities and α-synuclein pathology, offering potential therapeutic insights for Parkinson's disease. [Read the Full Post]

Vascular smooth muscle cell mechanotransduction through serum and glucocorticoid inducible kinase-1 promotes interleukin-6 production and macrophage accumulation in murine hypertension

220 | Dec 27 2023

The investigation demonstrated that mechanical activation of serum and glucocorticoid-inducible kinase-1 (SGK-1) in aortic vascular smooth muscle cells (VSMCs), both in vivo in hypertensive mice and in vitro through cyclic stretch, promotes inflammatory signaling and macrophage accumulation, suggesting SGK-1 as a potential pharmacotherapeutic target for hypertensive vascular pathology. [Read the Full Post]

Predictive model for treatment outcomes of peripheral T-cell lymphoma, not otherwise specified, in Taiwanese patients

352 | Dec 20 2023

In this retrospective study of 104 peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) patients in Taiwan, the investigation revealed a poor prognosis, highlighted the potential efficacy of pralatrexate as salvage chemotherapy for eligible patients, identified adverse prognostic factors, and proposed a novel predictive index with distinct risk groups, emphasizing the need for further validation and exploration of improved treatment strategies. [Read the Full Post]

YBX1-interacting small RNAs and RUNX2 can be blocked in primary bone cancer using CADD522

192 | Dec 20 2023

The study reveals that transfer RNA-derived small RNAs, specifically tRF-GlyTCC, function as a constitutive tumor suppressor mechanism in primary bone cancer, attenuating pro-metastatic protein-RNA interactions by targeting RUNX2 via a shared sequence motif with YBX1, leading to the development of the therapeutic agent CADD522 with significant efficacy in reducing tumor progression and metastasis in PBC. [Read the Full Post]

GRP78 acts as a cAMP/PKA signaling modulator through the MC4R pathway in porcine embryonic development

368 | Dec 17 2023

In this study, inhibiting Glucose-regulated protein 78 (GRP78) function using HA15 during porcine embryonic development disrupted the MC4R pathway, downregulated cAMP/PKA signaling, inhibited cell cycle progression, and induced mitochondrial dysfunction, revealing the crucial role of GRP78 in regulating these processes. [Read the Full Post]

miR-6071 inhibits hepatocellular carcinoma progression via targeting PTPN11

141 | Dec 17 2023

The study reveals that miR-6071 functions as a crucial regulator by targeting PTPN11, inhibiting liver cancer stem cells' self-renewal and tumorigenesis, and sensitizing hepatocellular carcinoma cells to lenvatinib treatment, making it a potential therapeutic target and predictive biomarker for postoperative lenvatinib therapy. [Read the Full Post]

Aberrant PI3Kδ splice isoform as a potential biomarker and novel therapeutic target for endocrine cancers

186 | Dec 15 2023

**Utilizing PI3Kδ-S as a Prognostic Biomarker and Therapeutic Target Offers a Promising Strategy for Advanced Endocrine Cancers.** [Read the Full Post]

Molecular Profiling and Targeted Therapies in Gliomas

130 | Dec 14 2023

This review explores the pivotal role of molecular profiling in the diagnosis, classification, and targeted treatment of gliomas, highlighting recent advances, challenges including the blood-brain barrier and tumor heterogeneity, and the pressing need for ongoing research to fully unlock the potential of personalized therapies for glioma patients. [Read the Full Post]

Indoximod-based chemo-immunotherapy for pediatric brain tumors: a first-in-children phase 1 trial

178 | Dec 12 2023

The Phase 1 trial of indoximod, an IDO-pathway inhibitor, in combination with chemotherapy and radiation, demonstrated favorable tolerability, significant objective responses, and encouraging immune responses in children with recurrent brain tumors, providing a basis for advancing to Phase 2/3 trials for pediatric brain tumors. [Read the Full Post]

Pediatric glioblastoma cells are sensitive to drugs that inhibit eIF2α dephosphorylation and its phosphomimetic S51D variant

111 | Dec 11 2023

The study demonstrates that combinations of histone deacetylase inhibitors and PARP-1 inhibitors, along with drugs increasing P-eIF2α or modulating its downstream effects, could be a promising and novel approach for treating pediatric glioblastoma (PED-GBM), particularly in cases with specific mutations. [Read the Full Post]

Supervised screening of Tecovirimat-like compounds as potential inhibitors for the monkeypox virus E8L protein

301 | Dec 10 2023

The study utilized computational methods and machine learning-guided screening to identify five promising drugs, ABX-1431, Alflutinib, Avacopan, Caspitant, and Darapalib, which effectively engage the MPXV E8L surface binding protein with higher affinity than Tecovirimat, potentially offering new avenues for the development of personalized treatments for Monkeypox virus infections. [Read the Full Post]

Transcriptomics-Guided In Silico Drug Repurposing: Identifying New Candidates with Dual-Stage Antiplasmodial Activity

391 | Dec 08 2023

The research effort identified two promising compounds, HSP-990 and silvestrol aglycone, demonstrating potent inhibitory activity at nanomolar concentrations against the asexual blood stage of Plasmodium falciparum, with silvestrol aglycone showing low cytotoxicity and transmission-blocking potential, indicating their potential as dual-acting antimalarial and transmission-blocking candidates for malaria control. [Read the Full Post]

Selective inhibition of indoleamine and tryptophan 2,3-dioxygenases: Comparative study on kynurenine pathway in cell lines via LC-MS/MS-based targeted metabolomics

131 | Dec 06 2023

This paper presents a validated LC-MS/MS method to quantify multiple metabolites in the kynurenine pathway, enabling the characterization of cell secretome, insights into disease scenarios, evaluation of enzyme inhibitors, and multivariate analysis, thereby advancing our understanding of cancer immunotherapy and preclinical drug research. [Read the Full Post]

Hepatic arterial infusion chemotherapy with or without lenvatinib for unresectable cholangiocarcinoma: a single-center retrospective study

238 | Dec 05 2023

**Combining FOLFOX hepatic arterial infusion chemotherapy with lenvatinib significantly prolongs overall and progression-free survival, making it a promising and safe treatment option for patients with unresectable cholangiocarcinoma.** [Read the Full Post]

Allelopathic Effect of Aqueous Extracts of Grass Genotypes on Eruca Sativa L

80 | Dec 03 2023

The study investigates the allelopathic activity of fifty grass genotypes and identifies phenolic compounds, particularly caffeic acid, in Festulolium genotypes, demonstrating their potent inhibitory effect on the growth of Eruca sativa L., highlighting their potential for sustainable weed control in agriculture. [Read the Full Post]

Low WIP1 Expression Accelerates Ovarian Aging by Promoting Follicular Atresia and Primordial Follicle Activation

99 | Nov 30 2023

Decreased wild-type P53-induced phosphatase 1 (WIP1) expression accelerates ovarian aging by promoting excessive follicular atresia, primordial follicle activation, and granulosa cell death, leading to irregular estrous cycles, fertility decline, and reduced ovarian reserve in mice. [Read the Full Post]

Regional regulatory harmonisation initiatives: Their potential contribution to the newly established African medicines agency

509 | Nov 30 2023

The study highlights the foundational role of regional medicines regulatory harmonization programs, such as the African Medicines Regulatory Harmonisation (AMRH) and East African Community Medicines Regulatory Harmonisation (EAC-MRH) initiatives, in supporting the operationalization of the African Medicine Agency (AMA), emphasizing the importance of strong national regulatory authorities and increased ratification of the AMA Treaty for ensuring access to essential medical products and technologies for the African people. [Read the Full Post]

Finding Lead Compounds for Dengue Antivirals from a Collection of Old Drugs through In Silico Target Prediction and Subsequent In Vitro Validation

178 | Nov 30 2023

This study utilized ligand-based and proteochemometric prediction models, coupled with experimental assays and molecular docking, to identify and validate potential DENV NS3 inhibitors, highlighting five promising lead compounds (ziltri, zilool, zileuton, linalool, and trimethadione) for further development as antiviral treatments. [Read the Full Post]

Lauric Acid, a Dietary Saturated Medium-Chain Fatty Acid, Elicits Calcium-Dependent Eryptosis

156 | Nov 29 2023

The study demonstrates that lauric acid induces eryptosis, a programmed cell death in red blood cells, and disrupts leukocyte distribution, providing key insights into its role in cardiovascular diseases and informing dietary interventions for prevention and management. [Read the Full Post]

Cytoplasmic Hsp70s promote EcR transport into the nucleus by responding to various stimuli

348 | Nov 27 2023

This study reveals that cytoplasmic Hsp70s facilitate the transport of the ecdysone receptor (EcR) into the nucleus in response to diverse stimuli, shedding light on the intricate mechanisms underlying insect metamorphosis and highlighting potential applications in pest control and broader biological research. [Read the Full Post]

Inhibition of Diacylglycerol Acyltransferase 2 Versus Diacylglycerol Acyltransferase 1: Potential Therapeutic Implications of Pharmacology

182 | Nov 26 2023

DGAT2 inhibitors, exemplified by ervogastat, offer a promising and well-tolerated therapeutic approach for patients with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and NASH with liver fibrosis, in contrast to limited efficacy and adverse effects associated with DGAT1 inhibitors. [Read the Full Post]

Topical non-aqueous nanoemulsion of Alpinia galanga extract for effective treatment in psoriasis: In vitro and in vivo evaluation

81 | Nov 24 2023

A non-aqueous nanoemulsion of Alpinia galanga extract, optimized using a Box-Behnken design, exhibited a 10-fold increase in skin permeation compared to the extract alone, confirming its efficacy in ameliorating psoriasis in an IMQ-induced mouse model via trans-follicular transport mechanism. [Read the Full Post]

Repeated Mild Traumatic Brain Injury and JZL184 Produce Sex-Specific Increases in Anxiety-Like Behavior and Alcohol Consumption in Wistar Rats

80 | Nov 24 2023

Repeated mild traumatic brain injury (rmTBI) increased alcohol consumption in female rats, had varying effects on anxiety-like behavior in males and females, and systemic treatment with JZL184 did not consistently mitigate these behavioral changes, revealing robust sex differences in rmTBI effects. [Read the Full Post]

FABP4 mediates endoplasmic reticulum stress and autophagy to regulate endometrial epithelial cell function during early sheep gestation

91 | Nov 22 2023

FABP4 regulates crucial processes such as cell migration, endoplasmic reticulum stress, and autophagy in sheep endometrial cells during early pregnancy, emphasizing its significance in orchestrating the establishment of pregnancy in ruminants. [Read the Full Post]

Doxorubicin resistance in breast cancer is mediated via the activation of FABP5/PPARγ and CaMKII signaling pathway

56 | Nov 21 2023

The study identifies FABP5 as a pivotal mediator of Doxorubicin resistance in breast cancer, demonstrating its potential as a targetable biomarker for therapeutic interventions aimed at overcoming chemoresistance. [Read the Full Post]

Identification of circRNA-miRNA-mRNA network regulated by Hsp90 in human melanoma A375 cells

310 | Nov 21 2023

The study reveals that targeting the ECM-receptor interaction pathway, specifically the integrin (ITG) and collagen (COL) network, following Hsp90 inhibition by SNX-2112, offers a promising and novel therapeutic approach for melanoma treatment. [Read the Full Post]

Dimeric Lectin Chimeras as Novel Candidates for Gb3-Mediated Transcytotic Drug Delivery through Cellular Barriers

131 | Nov 19 2023

The study presents a novel dimeric LecA chimera, Di-LecA, paired with the host cell glycosphingolipid Gb3, demonstrating efficient transcytosis across Gb3-positive cellular barriers, offering a promising strategy for targeted drug delivery applications. [Read the Full Post]

Heat shock factor 1 is a promising therapeutic target against adult T-cell leukemia

432 | Nov 18 2023

Targeting the overexpressed heat shock factor 1 (HSF1) with the inhibitor KRIBB11 inhibits proliferation, induces apoptosis, disrupts essential signaling pathways, and sensitizes adult T-cell leukemia cells to HSP90 inhibition, offering a potential therapeutic approach for ATL. [Read the Full Post]

Drug Repurposing Analysis for Colorectal Cancer through Network Medicine Framework: Novel Candidate Drugs and Small Molecules

165 | Nov 18 2023

The study identified a novel gene module associated with colorectal cancer and proposed several previously studied (including polyethylene glycol, pantoprazole, trametinib) and novel (such as lornoxicam, suxamethonium, HDAC6 inhibitor ISOX) drug-repurposing candidates based on network biology approaches and differential co-expression analysis. [Read the Full Post]

Stearoyl-CoA desaturase-1 is required for flavivirus RNA replication

97 | Nov 15 2023

Stearoyl-CoA desaturase-1 (SCD1) inhibitors, such as MK8245 and #1716, have shown potent and broad-spectrum suppression of Dengue virus replication, suggesting their potential as novel antiviral candidates for treating dengue fever and related flavivirus infections. [Read the Full Post]

FASN inhibition targets multiple drivers of NASH by reducing steatosis, inflammation and fibrosis in preclinical models

157 | Nov 15 2023

FASN inhibition demonstrates promising potential as a therapeutic strategy for NASH by targeting multiple hallmarks of the disease, including reducing hepatic fat accumulation, mitigating inflammation, and attenuating fibrosis. [Read the Full Post]

HSP70 attenuates neuronal necroptosis through the HSP90α-RIPK3 pathway following neuronal trauma

298 | Nov 14 2023

Activation of HSP70 protects against necroptosis in neuronal trauma, with HSP90α-mediated regulation of RIPK3 and MLKL contributing to this protective effect. [Read the Full Post]

Repurposing a tricyclic antidepressant in tumor and metabolism disease treatment through fatty acid uptake inhibition

80 | Nov 12 2023

The study revealed that nortriptyline, an FDA-approved tricyclic antidepressant, inhibits fatty acid uptake by inducing lysosomal acidification and suppressing macropinocytosis, offering a potential strategy to control cellular fatty acid levels and address conditions such as tumor growth, lipogenesis, and hepatic steatosis. [Read the Full Post]

Targeting Heat Shock Protein 27 and Fatty Acid Oxidation Augments Cisplatin Treatment in Cisplatin-Resistant Ovarian Cancer Cell Lines

119 | Nov 09 2023

Inhibition of heat shock protein 27 (HSP27) and fatty acid oxidation (FAO) in cisplatin-resistant ovarian cancer cells increases reactive oxygen species (ROS) production and sensitizes them to cisplatin treatment, while in vivo experiments show enhanced cytotoxicity of cisplatin when combined with HSP27 and FAO inhibition, suggesting potential therapeutic strategies to overcome cisplatin resistance. [Read the Full Post]

Peripheral Arterial Thrombosis following Russell's Viper Bites

161 | Nov 08 2023

This study reports three serious cases of peripheral arterial thrombosis following Russell's viper bites, emphasizing the significance of this complication in snakebite victims, while providing clinical management insights and mechanistic understanding of the procoagulant effects of Russell's viper venom. [Read the Full Post]

Targeting GSTP1 as Therapeutic Strategy against Lung Adenocarcinoma Stemness and Resistance to Tyrosine Kinase Inhibitors

292 | Nov 07 2023

The study reveals that upregulation of Glutathione S-transferase pi (GSTP1) in lung adenocarcinoma (LUAD) supports cancer stem cells, tumor self-renewal, metastasis, and resistance to targeted therapies, making it a promising therapeutic target for long-term control of LUAD. [Read the Full Post]

GRP78 Inhibitor YUM70 Suppresses SARS-CoV-2 Viral Entry, Spike Protein Production and Ameliorates Lung Damage

252 | Nov 04 2023

The study demonstrated that the small molecule inhibitor YUM70, which targets the GRP78 protein, effectively blocked SARS-CoV-2 viral entry and infection in vitro and in vivo, suggesting its potential as a promising therapeutic approach against COVID-19 and its variants. [Read the Full Post]

The role of serotonin inhibition within the treatment of carcinoid syndrome

107 | Nov 04 2023

Carcinoid syndrome, characterized by symptoms such as diarrhea, flushing, and abdominal pain, is primarily managed through the use of somatostatin analogues, surgical resection for potential cure, and other therapies such as loco-regional interventional radiological procedures, peptide receptor radionuclide therapy, and targeted medications. [Read the Full Post]

Regulation of pericyte metabolic reprogramming restricts the AKI to CKD transition

96 | Nov 04 2023

Metabolic reprogramming, characterized by decreased fatty acid oxidation and increased glycolysis, plays a critical role in pericyte-myofibroblast transition and targeting pericyte metabolism may prevent the progression of acute kidney injury to chronic kidney disease. [Read the Full Post]

Statins protect mice from high-decibel noise-induced hearing loss

119 | Nov 04 2023

The study found that direct delivery of fluvastatin to the cochlea and oral administration of lovastatin showed potential protective effects against noise-induced hearing loss in CBA/CaJ mice, as evidenced by reduced threshold shifts in auditory brainstem responses. [Read the Full Post]

Navoximod modulates local HSV-1 replication to reshape tumor immune microenvironment for enhanced immunotherapy via an injectable hydrogel

177 | Nov 03 2023

The combination of Navoximod and HSV-1 loaded in an injectable hydrogel (V-Navo@gel) shows promise in enhancing viral replication, reshaping the tumor microenvironment, and improving therapeutic outcomes in hepatocellular carcinoma and rabbit orthotopic liver cancer models. [Read the Full Post]

Novel pharmacotherapy targeting the positive symptoms of schizophrenia

82 | Nov 02 2023

This manuscript provides an updated overview of novel pharmacotherapy targeting positive symptoms in schizophrenia, highlighting promising compounds and alternative biological systems for future research. [Read the Full Post]

Significance of PBRM1 mutation in disease progress and drug selection in clear cell renal cell carcinoma

122 | Nov 02 2023

This study highlights the high prevalence of PBRM1 mutation in ccRCC, its association with advanced disease stages, and identifies potential therapeutic targets and pathways for personalized treatment. [Read the Full Post]

Improving the quality of multi-layer films based on furcellaran by immobilising active ingredients and impact assessment of the use of a new packaging material

94 | Nov 02 2023

The study developed multi-layer films incorporating furcellaran and active ingredients, which showed improved water properties, inhibited microbial growth, but had limited effects on lipid oxidation, thus exhibiting potential as active packaging materials for extending the shelf-life of fish products. [Read the Full Post]

Alox15/15-HpETE Aggravates Myocardial Ischemia-Reperfusion Injury by Promoting Cardiomyocyte Ferroptosis

90 | Nov 01 2023

The study revealed that Alox15-mediated cardiomyocyte ferroptosis is a crucial factor in prolonged myocardial ischemia-reperfusion injury, and inhibiting Alox15 can protect the myocardium and promote cardiac function recovery. [Read the Full Post]

Regulated IRE1α-dependent decay (RIDD)-mediated reprograming of lipid metabolism in cancer

206 | Nov 01 2023

Inhibition of IRE1α in triple negative breast cancer cells leads to DGAT2-dependent accumulation of triacylglycerols (TAGs) and sensitizes the cells to nutritional stress, highlighting the importance of IRE1α RIDD activity in reprogramming cellular lipid metabolism. [Read the Full Post]

Gram-Scale Preparation of Cannflavin A from Hemp ( Cannabis sativa L.) and Its Inhibitory Effect on Tryptophan Catabolism Enzyme Kynurenine-3-Monooxygenase

98 | Nov 01 2023

Cannflavin A (CFA), a compound derived from Cannabis sativa, has been shown to effectively inhibit kynurenine-3-monooxygenase (KMO), an enzyme in the neurotoxic kynurenine pathway (KP), indicating its potential as a therapeutic agent for neuroinflammatory and neurodegenerative disorders related to KP metabolites. [Read the Full Post]

Iron overload due to SLC40A1 mutation of type 4 hereditary hemochromatosis

211 | Oct 30 2023

The reported case of hereditary hemochromatosis type 4B involving a SLC40A1 gene mutation was effectively treated with monthly red blood cell apheresis followed by oral deferasirox therapy. [Read the Full Post]

Tryptophan metabolism induced by TDO2 promotes prostatic cancer chemotherapy resistance in a AhR/c-Myc dependent manner

516 | Oct 25 2023

Elevated expression of tryptophan 2,3-dioxygenase 2 (TDO2) promotes tryptophan metabolism and kynurenine production, activating the AhR/c-Myc/ABC-SLC transporters signaling pathway and contributing to chemoresistance in prostatic cancer. [Read the Full Post]

[ANMCO Expert opinion: Bempedoic acid place in therapy for hypercholesterolemia management]

215 | Oct 24 2023

Bempedoic acid, a newly approved therapeutic option for hypercholesterolemia, offers a hepatic selective action that reduces the risk of muscle adverse effects, making it particularly useful in certain clinical settings according to an ANMCO document. [Read the Full Post]

EGR1-mediated metabolic reprogramming to oxidative phosphorylation contributes to ibrutinib resistance in B cell lymphoma

306 | Oct 24 2023

The study identifies EGR1-mediated metabolic reprogramming to oxidative phosphorylation as a key mechanism driving ibrutinib resistance in B cell malignancies, suggesting that targeting this pathway with agents like metformin or IM156 could provide a potential therapeutic strategy to overcome acquired drug resistance in relapsed/refractory DLBCL or MCL. [Read the Full Post]

ADME Prediction, Structure-activity Relationship of Boswellic Acid Scaffold for the Aspect of Anticancer & Anti-inflammatory Potency

85 | Oct 22 2023

Boswellic acid and its analogs, particularly 11-keto-β-boswellic acid (KBA) and 3-O-acetyl-11-keto-β-boswellic acid (AKBA), exhibit promising therapeutic potential as anti-inflammatory and anticancer agents, with computational ADME prediction and structure-activity relationship analysis providing valuable insights into their pharmacokinetics and biological effects. [Read the Full Post]

[p53 regulates primordial follicle activation through the mTOR signaling pathway]

511 | Oct 22 2023

This study demonstrated that p53 inhibits primordial follicle activation through the mTOR signaling pathway, thereby maintaining the reserve of primordial follicles. [Read the Full Post]

Lipid profile changes associated with antiretroviral therapies in a real-world cohort

84 | Oct 21 2023

In this retrospective cohort study, treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate was associated with a significant worsening of the lipid profile compared to dolutegravir/abacavir/lamivudine, but no significant differences in cardiovascular events were observed between the two treatment groups. [Read the Full Post]

Targeting lipid-sensing nuclear receptors PPAR (α, γ, β/δ): HTVS and molecular docking/dynamics analysis of pharmacological ligands as potential pan-PPAR agonists

204 | Oct 19 2023

The study identified eprosartan as a potential PPAR pan-agonist with strong binding affinity to all PPAR isoforms, demonstrated superior stability in protein-ligand complex formation, and showed promising therapeutic effects in an in vitro model of NAFLD. [Read the Full Post]

Updates and advances in pyruvate kinase deficiency

102 | Oct 19 2023

Mutations in the PKLR gene lead to pyruvate kinase deficiency, causing chronic hemolytic anemia, and recent advancements in treatment options include the use of an oral allosteric PK activator called mitapivat and ongoing clinical trials for gene therapy. [Read the Full Post]

Dual roles of β-arrestin 1 in mediating cell metabolism and proliferation in gastric cancer

115 | Oct 18 2023

The study demonstrates that β-Arrestin 1 (ARRB1) plays a crucial role in gastric cancer cell metabolism and proliferation, with its subcellular localization determining its dual functions and suggesting the therapeutic potential of targeting the ARRB1-PKM2 axis. [Read the Full Post]

Tumor-Suppressive Effect of Metformin via the Regulation of M2 Macrophages and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment of Colorectal Cancer

190 | Oct 17 2023

Metformin inhibits the populations of myeloid-derived suppressor cells (MDSCs) and M2 macrophages in the tumor microenvironment of colon cancers through AMPK activation, mTOR inhibition, and downregulation of the mevalonate pathway. [Read the Full Post]

With-No-Lysine Kinase 1 (WNK1) Augments TRPV4 Function in the Aldosterone-Sensitive Distal Nephron

207 | Oct 11 2023

WNK1 kinase plays a critical role in regulating TRPV4 activity and expression, essential for maintaining potassium homeostasis in the aldosterone-sensitive distal nephron. [Read the Full Post]

Construction and Validation of Protein Expression-related Prognostic Models in Clear Cell Renal Cell Carcinoma

321 | Oct 10 2023

The study developed a prognostic evaluation model for ccRCC patients using bioinformatics methods, identified 13 independent prognostic proteins, and demonstrated their strong predictive ability for patient survival, while also identifying potential drugs for targeted therapy. [Read the Full Post]

Advances into Understanding the Vital Role of the Mitochondrial Citrate Carrier (CIC) in Metabolic Diseases

109 | Oct 09 2023

This paper provides a comprehensive overview of the structure, function, and disease associations of the mitochondrial citrate carrier (CIC), highlighting its potential as a novel therapeutic target in a range of human metabolic diseases. [Read the Full Post]

The Functional Role and Regulatory Mechanism of FTO m6A RNA Demethylase in Human Uterine Leiomyosarcoma

314 | Oct 08 2023

In summary, the study highlights the aberrant upregulation of FTO m6A RNA demethylase in uterine leiomyosarcoma tissues and demonstrates that inhibiting FTO with Dac51 can significantly decrease uLMS cell proliferation, modulate key pathways, and potentially offer a novel therapeutic strategy for this aggressive uterine cancer. [Read the Full Post]

Bioassay-Guided Isolation of Anthelmintic Components from Semen pharbitidis, and the Mechanism of Action of Pharbitin

71 | Oct 07 2023

This study identified the anthelmintic compound pharbitin from Semen pharbitidis and revealed that its target in Caenorhabditis elegans is likely UNC-63, supporting the traditional use of Semen pharbitidis for treating intestinal parasites. [Read the Full Post]

Discovery of a novel RIPK2 inhibitor for the treatment of inflammatory bowel disease

172 | Oct 03 2023

The novel RIPK2 inhibitor Zharp2-1 shows promising potential for the treatment of inflammatory bowel disease (IBD) based on its ability to effectively block RIPK2 kinase function, inhibit NOD-mediated signaling, and ameliorate colitis symptoms in preclinical studies. [Read the Full Post]

Design of OSMI-4 Analogs Using Scaffold Hopping: Investigating the Importance of the Uridine Mimic in the Binding of OGT Inhibitors

203 | Sep 29 2023

This study introduces a modified peptide part of OSMI-4 and incorporates new sulfonamide UDP mimics to design and evaluate a small library of OSMI-4 derivatives, providing insights into the OGT binding pocket and its specificity towards quinolone-4-carboxamides. [Read the Full Post]

Beta-endoproteolysis of the cellular prion protein by dipeptidyl peptidase-4 and fibroblast activation protein

235 | Sep 28 2023

This study identified fibroblast activation protein (FAP) and dipeptidyl peptidase-4 (DPP4) as proteases responsible for cleaving the cellular prion protein (PrPC), with their activity and modulation affecting the physiology and pathogenic potential of PrPC and its associated diseases. [Read the Full Post]

ZBTB7C m6A modification incurred by METTL3 aberration promotes osteosarcoma progression

108 | Sep 25 2023

The study reveals that elevated METTL3 and increased m6A modification, particularly on ZBTB7C mRNA, play a crucial role in promoting osteosarcoma progression, suggesting that targeting the METTL3/ZBTB7C axis could be a potential therapeutic strategy. [Read the Full Post]

Synergistic apoptosis by combination of metformin and an O-GlcNAcylation inhibitor in colon cancer cells

105 | Sep 24 2023

The combinatorial treatment of metformin and OSMI-1 synergistically induced apoptosis in colon cancer cells by enhancing ER stress-induced signaling and disrupting autophagy, as evidenced by in vitro and xenograft tumor experiments. [Read the Full Post]

Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial

257 | Sep 23 2023

The MMPOWER-3 trial evaluating the efficacy of elamipretide in individuals with Primary Mitochondrial Myopathies did not show significant improvements in physical function and fatigue but established the drug's safety and tolerability. [Read the Full Post]

Identifying responders to elamipretide in Barth syndrome: Hierarchical clustering for time series data

149 | Sep 23 2023

This proof-of-concept study demonstrated that wearable device data can predict functional status and response to elamipretide treatment in patients with Barth syndrome (BTHS). [Read the Full Post]

Clinicopathological Features and Outcomes of Granulosa Cell Tumor of the Ovaries - A Retrospective Study

91 | Sep 22 2023

This retrospective analysis of granulosa cell tumors found that post-menopausal patients, advanced disease at presentation, and various factors related to surgical resection were associated with poorer outcomes, while the median disease-free survival was 60 months and overall survival was 62 months. [Read the Full Post]

Simultaneous quantitation of oxidized and reduced glutathione via LC-MS/MS to study the redox state and drug-mediated modulation in cells, worms and animal tissue

88 | Sep 22 2023

This study presents an optimized LC-MS/MS method for quantifying GSH and GSSG levels in different biological matrices, offering high sensitivity and throughput for assessing oxidative stress and potential disease progression in toxicological research. [Read the Full Post]

Atomic model for core modifying region of human fatty acid synthase in complex with Denifanstat

92 | Sep 21 2023

Researchers have developed an engineered full-length human Fatty Acid Synthase (hFASN) protein, enabling the study of specific regions involved in fatty acid modification and providing insights for the design of small molecule inhibitors targeting hFASN in diseases such as diabetes, cancer, fatty liver diseases, and viral infections. [Read the Full Post]

The synthetic oleanane triterpenoid CDDO-2P-Im binds GRP78/BiP to induce unfolded protein response-mediated apoptosis in myeloma

344 | Sep 21 2023

The study demonstrates that the synthetic oleanane triterpenoid 2P-Im induces apoptosis in multiple myeloma cells through activation of the unfolded protein response (UPR) and direct binding to the endoplasmic reticulum chaperone BiP (GRP78/BiP). [Read the Full Post]

Iron Chelator VLX600 Inhibits Mitochondrial Respiration and Promotes Sensitization of Neuroblastoma Cells in Nutrition-Restricted Conditions

247 | Sep 17 2023

The iron chelator VLX600 inhibits mitochondrial respiration, reduces MYCN/LMO1 expression, and induces cell death in neuroblastoma cells, regardless of MYCN status, suggesting its potential as a therapeutic agent in combination with conventional chemotherapy for the treatment of neuroblastoma. [Read the Full Post]

A small molecule G6PD inhibitor reveals immune dependence on pentose phosphate pathway

247 | Sep 16 2023

The study developed a small molecule inhibitor, G6PDi-1, that effectively targets the glucose-6-phosphate dehydrogenase (G6PD) enzyme and modulates immune responses by depleting NADPH and inhibiting inflammatory cytokine production in T cells while suppressing respiratory burst in neutrophils. [Read the Full Post]

Metabolic Flux Analysis Reveals the Roles of Stearate and Oleate on CPT1C-mediated Tumor Cell Senescence

92 | Sep 15 2023

The study demonstrates that manipulating the stearate/oleate ratio through inhibition of SCD-1, along with depletion of CPT1C, could be a promising strategy for cancer therapy by inducing tumor cell senescence and inhibiting proliferation. [Read the Full Post]

Diverse Mechanisms of Resistance against Osimertinib, a Third-Generation EGFR-TKI, in Lung Adenocarcinoma Cells with an EGFR-Activating Mutation

114 | Sep 14 2023

The study identified multiple mechanisms of osimertinib resistance in EGFR-mutant NSCLC cells, including wild-type EGFR amplification, KRAS amplification and mutation, dependence on EGFR and IGF1R signaling, Bid cleavage for apoptosis induction, and a SHP2/T507K mutation activating the ERK1/2 pathway, suggesting potential therapeutic strategies for overcoming resistance. [Read the Full Post]

Norepinephrine as the Intrinsic Contributor to Contact Lens-Induced Pseudomonas aeruginosa Keratitis

323 | Sep 11 2023

This study reveals that norepinephrine, acting through the β2-adrenergic receptor, promotes Pseudomonas aeruginosa keratitis during contact lens wear, suggesting potential therapeutic targets for treating the condition. [Read the Full Post]

Inhibition-of-BUB1-Kinase-by-BAY-1816032-Sensitizes-Tumor-Cells-toward-Taxanes-ATR-and-PARP-Inhibitors-In-Vitro-and-In-Vivo

245 | Sep 11 2023

The study revealed that overexpression of BUB1 in osteosarcoma is associated with poor clinical outcomes and that inhibiting BUB1 significantly suppresses tumor growth and metastasis while inducing apoptosis, highlighting its potential as a therapeutic target. [Read the Full Post]

Activation of the integrated stress response (ISR) pathways in response to Ref-1 inhibition in human pancreatic cancer and its tumor microenvironment

204 | Sep 09 2023

Inhibition of Ref-1 redox signaling and activation of the integrated stress response (ISR) pathway through eIF2 phosphorylation could represent a promising therapeutic approach for treating pancreatic ductal adenocarcinoma (PDAC). [Read the Full Post]

[18F]ONO-8430506: A novel radioligand for PET imaging of autotaxin (ATX)

77 | Sep 07 2023

The novel radioligand [18F]ONO-8430506 ([18F]8) showed promising inhibitory potency against ATX but exhibited relatively low tumor uptake and retention in PET imaging studies. [Read the Full Post]

Ziritaxestat, a Novel Autotaxin Inhibitor, and Lung Function in Idiopathic Pulmonary Fibrosis: The ISABELA 1 and 2 Randomized Clinical Trials

172 | Sep 07 2023

The phase 3 clinical trials of ziritaxestat, an autotaxin inhibitor, showed no improvement in clinical outcomes compared to placebo in patients with idiopathic pulmonary fibrosis (IPF), regardless of whether they were receiving standard of care treatment or not. [Read the Full Post]

ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model

195 | Sep 05 2023

The ACL inhibitor BMS-303141 effectively attenuated ectopic lipid accumulation and improved renal injuries in db/db mice, suggesting its potential as a therapeutic treatment for obesity-related renal complications. [Read the Full Post]

Genomic and biological aspects of resistance to selective poly(ADP-ribose) glycohydrolase inhibitor PDD00017273 in human colorectal cancer cells

93 | Sep 04 2023

The study identified specific mutations in PARG and PARP1, resulting in structural modifications and downregulation of PARP1, leading to resistance to the PARG inhibitor PDD00017273 in HCT116RPDD cells. [Read the Full Post]

De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma

186 | Sep 01 2023

The discovery of the hypersensitivity of IDH1-mutant glioma cells to DHODH inhibitors presents a promising, biomarker-guided therapeutic strategy for the treatment of aggressive glioma. [Read the Full Post]

Investigating dihydroorotate dehydrogenase inhibitor mediated mitochondrial dysfunction in hepatic in vitro models

178 | Sep 01 2023

The study found that while DHODH inhibitors showed multifactorial toxicity and moderate indications of respiratory chain dysfunction or uncoupling in HepaRG® cells, leflunomide and brequinar specifically exhibited mitochondrial toxicity in HepG2 cells, indicating a potential role of biotransformation in mediating or masking hepatic mitochondrial liabilities. [Read the Full Post]

m6A demethylase FTO renders radioresistance of nasopharyngeal carcinoma via promoting OTUB1-mediated anti-ferroptosis

182 | Aug 31 2023

The upregulation of the m6A mRNA demethylase FTO in radioresistant nasopharyngeal carcinoma (NPC) promotes radiotherapy resistance by inhibiting radiation-induced ferroptosis, suggesting FTO as a potential therapeutic target and prognostic biomarker for NPC. [Read the Full Post]

PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis

236 | Aug 26 2023

The study identified multidrug-resistant CLL cells in patients and demonstrated that a small molecule activator of PP2A called DT-061 induced apoptosis in these cells independently of Bax/Bak, providing a potential strategy to overcome treatment resistance. [Read the Full Post]

Oxidative stress enhances the therapeutic action of a respiratory inhibitor in MYC-driven lymphoma

171 | Aug 23 2023

The combination of complex I inhibition and high-dose ascorbate demonstrates synergistic anticancer effects in MYC-driven cancers, such as high-grade lymphomas, by inducing oxidative stress and disrupting redox homeostasis. [Read the Full Post]

SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor

66 | Aug 22 2023

The study reveals that the protein SHP2 plays a critical role in decidualization, influencing the nuclear localization of the progesterone receptor and highlighting its potential involvement in recurrent miscarriage. [Read the Full Post]

Dichloroacetic acid and rapamycin synergistically inhibit tumor progression

436 | Aug 15 2023

Rapamycin treatment leads to the inactivation of the pyruvate dehydrogenase complex (PDHc) through mTOR signaling inhibition, reducing cancer cells' response to rapamycin, while reactivating PDHc with dichloroacetic acid (DCA) enhances their susceptibility to rapamycin treatment. [Read the Full Post]

Recombinant Treponema pallidum Protein Tp47 Promoted the Phagocytosis of Macrophages by Activating NLRP3 Inflammasome Induced by PKM2-Dependent Glycolysis

82 | Aug 15 2023

Tp47-induced activation of glycolysis and the NLRP3 inflammasome in macrophages promotes phagocytosis, with the upregulation of the M2 isoform of pyruvate kinase (PKM2) playing a crucial role in glycolysis-dependent NLRP3 activation. [Read the Full Post]

Hybrid Analogues of Hydrazone and Phthalimide: Design, Synthesis, In vivo, In vitro, and In silico Evaluation as Analgesic Agents

201 | Aug 15 2023

A new series of hybrid hydrazone and phthalimide compounds were synthesized and evaluated, showing significant analgesic activity, selective COX-2 inhibition, and favorable cytostatic properties with a high therapeutic index. [Read the Full Post]

Pharmacological inhibition of serine synthesis enhances temozolomide efficacy by decreasing O6-methylguanine DNA methyltransferase (MGMT) expression and reactive oxygen species (ROS)-mediated DNA damage in glioblastoma

69 | Aug 15 2023

The study found that the selective inhibitor NCT503, when combined with temozolomide (TMZ), demonstrated synergistic effects in inhibiting glioblastoma cell growth and inducing apoptosis, potentially offering a promising treatment strategy for MGMT-high glioblastoma patients. [Read the Full Post]

ACSS2-mediated NF-κB activation promotes alkaliptosis in human pancreatic cancer cells

158 | Aug 13 2023

ACSS2, an enzyme involved in acetyl-coenzyme A production and histone acetylation, has been identified as a positive regulator of alkaliptosis in human pancreatic ductal adenocarcinoma cells, potentially offering new therapeutic strategies for PDAC treatment. [Read the Full Post]

The expression and role of glycolysis-associated molecules in infantile hemangioma

217 | Aug 13 2023

This study demonstrates that glycolysis-associated molecules are highly expressed in infantile hemangioma endothelial cells, and their inhibition leads to a reduction in cell proliferation, migration, and tube formation, suggesting their potential as therapeutic targets for treating infantile hemangioma. [Read the Full Post]

Pharmacological induction of membrane lipid poly-unsaturation sensitizes melanoma to ROS inducers and overcomes acquired resistance to targeted therapy

103 | Aug 12 2023

The study demonstrates that combining MAPK inhibitors, FASN inhibitors, and ROS-inducing compounds increases lipid poly-unsaturation and overcomes therapy resistance, leading to improved survival in BRAF-mutant melanoma. [Read the Full Post]

SIRT3 ameliorates polycystic ovary syndrome through FOXO1/PGC-1α signaling pathway

99 | Aug 09 2023

The study demonstrates that SIRT3 regulates the FOXO1/PGC-1α signaling pathway, mitigating mitochondrial dysfunction and improving polycystic ovary syndrome (PCOS). [Read the Full Post]

Transformable prodrug nanoplatform via tumor microenvironment modulation and immune checkpoint blockade potentiates immunogenic cell death mediated cancer immunotherapy

209 | Aug 04 2023

In this study, a dual-responsive polymersomal prodrug nanoplatform was developed, combining CAF inhibition, ROS consumption, immune checkpoint blockade, and immunogenic cell death induction, leading to improved tumor regression and long-term immune memory response, offering potential for effective cancer treatment. [Read the Full Post]

NAD + Metabolism Generates a Metabolic Vulnerability in Endocrine-Resistant Metastatic Breast Tumors in Females

361 | Aug 03 2023

The study revealed that combining a NAMPT inhibitor with fulvestrant showed a synergistic effect in reducing metastatic tumor burden and reversing gene expression associated with aggressive tumor phenotypes in ER+ metastatic breast cancer, offering a promising strategy for treatment. [Read the Full Post]

Enhanced chemotherapeutic efficacy of docetaxel in human lung cancer cell line via GLUT1 inhibitor

147 | Aug 03 2023

The study demonstrated that co-administration of a GLUT1 inhibitor and docetaxel synergistically increased cytotoxicity and apoptosis in lung cancer cells, suggesting a promising therapeutic strategy for the treatment of lung cancer patients. [Read the Full Post]

Effects of Hypolipidemic Drugs on Psoriasis

307 | Aug 02 2023

The systematic review of 41 original articles assessed the effect of different hypolipidemic treatments on the course of psoriasis, highlighting the potential benefits of statins, fibrates, glitazones, and GLP-1 receptor agonists in improving lipid abnormalities associated with the disease. [Read the Full Post]

Bioinformatics screening of colorectal-cancer causing molecular signatures through gene expression profiles to discover therapeutic targets and candidate agents

311 | Aug 02 2023

This study utilized integrated statistics and bioinformatics approaches to identify key genes, transcriptional regulators, and candidate therapeutic agents for colorectal cancer (CRC), highlighting their potential diagnostic, prognostic, and therapeutic significance. [Read the Full Post]

Phase 1 pilot study of RRx-001 + nivolumab in patients with advanced metastatic cancer (PRIMETIME)

129 | Aug 01 2023

The phase 1 pilot study demonstrated that the combination of RRx-001 and nivolumab was well-tolerated, showed preliminary anti-cancer activity, and further clinical trials with this combination are warranted. [Read the Full Post]

ML390 inhibits enterovirus 71 replication by targeting de novo pyrimidine biosynthesis pathway

58 | Jul 31 2023

ML390, a dihydroorotate dehydrogenase inhibitor, demonstrates potent anti-EV71 activity by inhibiting viral replication through interference with the pyrimidine synthesis pathway, showing potential as a treatment for hand, foot, and mouth disease caused by EV71 infection. [Read the Full Post]

Sevoflurane induces neurotoxic effects on developing neurons through the WNK1/NKCC1/Ca2+ /Drp-1 signalling pathway

181 | Jul 30 2023

The study found that sevoflurane-induced neurotoxicity in hippocampal neuronal cells is mediated through the WNK1/NKCC1/Ca2+/Drp-1 signaling pathway, and inhibiting this pathway can alleviate cell viability reduction and apoptosis caused by sevoflurane exposure. [Read the Full Post]

Timely expression of PGAM5 and its cleavage control mitochondrial homeostasis during neurite re-growth after traumatic brain injury

227 | Jul 27 2023

The study reveals that phosphoglycerate mutase 5 (PGAM5) acts as a mitochondrial sensor in traumatic brain injury (TBI), promoting mitophagy and subsequent cleavage by PARL, leading to increased mitochondrial transcription factor A (TFAM) expression and functional recovery. [Read the Full Post]

pH-sensitive smart indicators based on cellulose and different natural pigments for tracing kimchi ripening stages

615 | Jul 27 2023

The study found that cellulose-based pH-sensitive indicators loaded with natural pigments showed more pronounced color changes in response to lactic acid and pH variations, with alkalized indicators being particularly effective for monitoring the fermentation process of acidic foods such as kimchi. [Read the Full Post]

Visfatin-induced upregulation of lipogenesis via EGFR/AKT/GSK3β pathway promotes breast cancer cell growth

114 | Jul 27 2023

Visfatin induces lipid synthesis and accumulation in breast cancer cells through activation of the EGFR/AKT/GSK3β pathway, promoting cell survival and proliferation. [Read the Full Post]

LATS-regulated nuclear-cytoplasmic translocation of SREBP2 inhibits hepatocellular carcinoma cell migration and invasion via epithelial-mesenchymal transition

105 | Jul 27 2023

The study demonstrates that high expression of SREBP2 in hepatocellular carcinoma (HCC) is associated with poor prognosis and promotes HCC cell invasion and metastasis through the epithelial-mesenchymal transition (EMT) process, suggesting SREBP2 as a potential therapeutic target for HCC. [Read the Full Post]

Efficacy and tolerability of isocitrate dehydrogenase inhibitors in patients with acute myeloid leukemia: A systematic review of clinical trials

59 | Jul 23 2023

Isocitrate dehydrogenase (IDH) inhibitors, particularly ivosidenib for IDH-1 and enasidenib for IDH-2 mutations, demonstrate safety and efficacy in treating newly diagnosed medically unfit or relapsed/refractory acute myeloid leukemia (AML) patients with IDH mutations, improving objective response rates and survival outcomes, although further studies are necessary to validate these findings and compare them with other targeted therapies. [Read the Full Post]

[Novel Strategies to Treat Acute Myeloid Leukemia]

62 | Jul 23 2023

Novel treatment strategies for acute myeloid leukemia (AML) based on patient-related and disease-specific factors, including targeted therapies, consolidation with chemotherapy or allogeneic hematopoietic cell transplantation, and maintenance therapy, show promise in improving outcomes for AML patients. [Read the Full Post]

Therapies for acute myeloid leukemia in patients ineligible for standard induction chemotherapy: a systematic review

194 | Jul 23 2023

Targeted therapy combined with a hypomethylating agent shows the most promising results in terms of overall survival and event-free survival for patients with acute myeloid leukemia (AML) who are ineligible for first-line induction chemotherapy, although combination therapies are associated with a higher incidence of adverse events. [Read the Full Post]

A phase Ib/II study of ivosidenib with venetoclax +/- azacitidine in IDH1-mutated myeloid malignancies

57 | Jul 23 2023

The combination of the IDH1 inhibitor ivosidenib, the BCL2 inhibitor venetoclax, and azacitidine demonstrated favorable safety and efficacy profiles, with high response rates, durable remissions, and potential benefits for patients with IDH1-mutated myeloid malignancies, including those with signaling gene mutations. [Read the Full Post]

Inhibition of Autotaxin Ameliorates LPA-Mediated Neuroinflammation and Alleviates Neurological Dysfunction in Acute Hepatic Encephalopathy

73 | Jul 23 2023

The study demonstrated that treatment with an autotaxin inhibitor attenuated neuroinflammation, reduced levels of LPA and inflammatory markers, improved neurobehavioral symptoms, and ameliorated brain edema in a mouse model of hepatic encephalopathy. [Read the Full Post]

Extracellular Release of Citrullinated Vimentin Directly Acts on Osteoclasts to Promote Bone Resorption in a Mouse Model of Periodontitis

272 | Jul 20 2023

The release of citrullinated vimentin (CV) promotes osteoclastogenesis and bone resorption in periodontitis, suggesting a potential shared pathogenesis with rheumatoid arthritis. [Read the Full Post]

The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase

0 | Jul 16 2023

The chromatin kinase VRK1 plays a crucial role in regulating the epigenetic patterns of histone H3 acetylation and methylation, thereby influencing chromatin organization and associated nuclear functions. [Read the Full Post]

Specific gene module pair-based target identification and drug discovery

0 | Jul 14 2023

The GMPTI method extracts target-induced gene modules to identify target signatures and predict novel compound-target interactions, leading to the discovery of novel inhibitors for three proteins in the PI3K pathway. [Read the Full Post]

PPARβ/δ Ligands Regulate Oxidative Status and Inflammatory Response in Inflamed Corpus Luteum-An In Vitro Study

174 | Jul 12 2023

This study revealed that PPARβ/δ agonists at different concentrations regulate the inflammatory response in the pig corpus luteum, with the lower dose showing anti-inflammatory effects and the higher dose potentially supporting the immune response against pathogens. [Read the Full Post]

Cyanidin inhibits adipogenesis in 3T3-L1 preadipocytes by activating the PLC-IP3 pathway

246 | Jul 11 2023

Cyanidin inhibits adipocyte formation by downregulating adipogenic marker gene expression and activating the PLC-IP3 pathway, leading to intracellular Ca2+ signaling. [Read the Full Post]

PCSK9 Inhibition Regulates Infarction-Induced Cardiac Myofibroblast Transdifferentiation via Notch1 Signaling

157 | Jul 09 2023

SBC-115076, a PCSK9 inhibitor, was found to mitigate cardiac fibrosis and improve ventricular function after myocardial infarction by inhibiting the differentiation of cardiac fibroblasts to myofibroblasts through the Notch1/Hes1 signaling pathway. [Read the Full Post]

Investigations into the Signaling Pathways Involving Glucose-Stimulated Zinc Secretion (GSZS) from Prostate Epithelial Cells In Vitro and In Vivo

90 | Jul 06 2023

Exposure of prostate cells to high glucose leads to glucose-stimulated zinc secretion (GSZS) both in vitro and in vivo, requiring glycolytic flux and involving the activation of specific signaling pathways. [Read the Full Post]

Targeting of Glucose Transport and the NAD Pathway in Neuroendocrine Tumor (NET) Cells Reveals New Treatment Options

185 | Jul 06 2023

In this study, the effectiveness of glucose transporter (GLUT) and nicotinamide phosphoribosyltransferase (NAMPT) inhibitors as potential treatments for neuroendocrine tumors (NET) was demonstrated through significant effects on tumor cell proliferation and survival rates. [Read the Full Post]

Anti-tumor effects of perampanel in malignant glioma cells

183 | Jul 05 2023

Perampanel, an antiepileptic drug, demonstrates potential antitumoral effects by inducing apoptosis and reducing cell viability, particularly when combined with temozolomide, in certain malignant glioma cell lines, suggesting new therapeutic strategies for the treatment of glioblastoma. [Read the Full Post]

The 15-hydroxyprostaglandin dehydrogenase inhibitor SW033291 ameliorates abnormal hepatic glucose metabolism through PGE2-EP4 receptor-AKT signaling in a type 2 diabetes mellitus mouse model

69 | Jul 04 2023

The study found that SW033291 treatment improved glucose metabolism, reduced lipid levels, and ameliorated insulin resistance in a T2DM mouse model, indicating its potential as a novel therapeutic agent for T2DM. [Read the Full Post]

Proteasome Inhibition Sensitizes Liposarcoma to MDM2 Inhibition with Nutlin-3 by Activating the ATF4/CHOP Stress Response Pathway

259 | Jul 03 2023

The study suggests that combining MDM2 inhibitors with proteasome inhibitors could improve the efficacy of treatment for liposarcoma by inducing apoptosis through activation of the ATF4/CHOP stress response axis. [Read the Full Post]

GSK484, an inhibitor of peptidyl arginine deiminase 4, increases the radiosensitivity of colorectal cancer and inhibits neutrophil extracellular traps

217 | Jun 30 2023

The study demonstrates that the PAD4 inhibitor GSK484 enhances the radiosensitivity of colorectal cancer, induces cell death, and inhibits neutrophil extracellular trap (NET) formation, suggesting its potential as a therapeutic agent for improving treatment outcomes in CRC. [Read the Full Post]

Modulation of blood-brain tumor barrier for delivery of magnetic hyperthermia to brain cancer

348 | Jun 25 2023

This proposed approach utilizes a polymeric nanocarrier to deliver fingolimod and modulate the blood-brain tumor barrier, allowing for targeted accumulation of magnetic nanoclusters and synergistic magnetic hyperthermia therapy for the treatment of glioblastoma [Read the Full Post]

Suppression of lung oxidative stress, inflammation and fibrosis following nitrogen mustard exposure by the selective farnesoid X receptor agonist obeticholic acid

126 | Jun 21 2023

Activation of the farnesoid X receptor (FXR) through treatment with obeticholic acid attenuates nitrogen mustard-induced lung injury, oxidative stress, inflammation, and fibrosis, suggesting FXR activation as a potential therapeutic strategy for limiting cytotoxic vesicant toxicity. [Read the Full Post]

PKM2/PDK1 dual-targeted shikonin derivatives restore the sensitivity of EGFR-mutated NSCLC cells to gefitinib by remodeling glucose metabolism

0 | Jun 12 2023

Compound E5, a dual inhibitor of PKM2/PDK1, demonstrates potent inhibitory activity against EGFR mutant NSCLC cells, exhibits good anti-tumor efficacy in xenografted mouse models, and shows potential as an adjunct to gefitinib in the treatment of EGFR-TKI-resistant NSCLC. [Read the Full Post]

Serum Neurofilament Light Chain in Patients With Atrial Fibrillation

97 | Jun 12 2023

Patients with atrial fibrillation (AF) exhibit elevated levels of serum neurofilament light chain (sNFL), a marker of neuroaxonal damage, compared to controls without AF, and ongoing AF rhythm is associated with even higher sNFL levels. [Read the Full Post]

Screening the Tocriscreen™ bioactive compound library in search for inhibitors of Candida biofilm formation

90 | Jun 12 2023

The study identified several compounds, including toyocamycin and darapladib, with potent biofilm inhibitory activity against Candida species, offering potential for the development of new clinically approved antifungal agents for the treatment of Candida biofilms. [Read the Full Post]

Dimethyloxalylglycine Attenuates Steroid-Associated Endothelial Progenitor Cell Impairment and Osteonecrosis of the Femoral Head by Regulating the HIF-1α Signaling Pathway

184 | Jun 11 2023

Targeting hypoxia-inducible factor-1α (HIF-1α) in endothelial progenitor cells (EPCs) may offer a novel therapeutic approach for the treatment of steroid-associated osteonecrosis of the femoral head (SONFH) by alleviating glucocorticoid-induced endothelial impairment, promoting angiogenesis and osteogenesis, and enhancing the homing of EPCs to the injured endothelium. [Read the Full Post]

Characterization of Plasmodium falciparum prohibitins as novel targets to block infection in humans by impairing the growth and transmission of the parasite

407 | Jun 08 2023

The study characterizes Plasmodium falciparum prohibitins (PHBs), showing their expression in both asexual and sexual blood stages and localization in mitochondria, and demonstrating their involvement in stabilizing mitochondrial DNA and maintaining integrity, with potential druggability for blocking parasite growth using Rocaglamide (Roc-A). [Read the Full Post]

Vascular lipid droplets formed in response to TNF, hypoxia, or OA: biochemical composition and prostacyclin generation

171 | Jun 05 2023

The study investigates the role of lipid droplets (LDs) and adipose triglyceride lipase (ATGL)-dependent prostacyclin (PGI2) generation in the response of endothelial cells to proinflammatory stimuli, demonstrating that LDs formation and ATGL-mediated PGI2 generation represent a universal response to vascular proinflammatory insult. [Read the Full Post]

AdipoRon Engages Microglia to Antinociception through the AdipoR1/AMPK Pathway in SNI Mice

281 | Jun 05 2023

AdipoRon may alleviate neuropathic pain by inhibiting microglia-derived TNF-α expression through the AdipoR1/AMPK pathway. [Read the Full Post]

Jmjd4 Facilitates Pkm2 Degradation in Cardiomyocytes and Is Protective Against Dilated Cardiomyopathy

142 | Jun 03 2023

The study found that Jmjd4 plays a critical role in maintaining metabolic homeostasis in adult cardiomyocytes by degrading Pkm2 and its deficiency may lead to DCM, which suggests that targeting Jmjd4 and Pkm2 may be a potential therapeutic strategy for DCM and other cardiac diseases with metabolic dysfunction. [Read the Full Post]

PKM2/PDK1 dual-targeted shikonin derivatives restore the sensitivity of EGFR-mutated NSCLC cells to gefitinib by remodeling glucose metabolism

114 | Jun 03 2023

The authors proposed a "two-step approach" to target both PKM2 and PDK1 simultaneously, and designed a novel PKM2/PDK1 dual-target agent E5, which showed promising anti-tumor activity and restored the sensitivity of EGFR-TKIs resistant NSCLC cells to gefitinib. [Read the Full Post]

NDUFS3 knockout cancer cells and molecular docking reveal specificity and mode of action of anti-cancer respiratory complex I inhibitors

368 | Jun 03 2023

This study highlights the need for cautious evaluation and dosage optimization of inhibitors targeting respiratory complex I in cancer treatment. [Read the Full Post]

Protective effects of gallic acid and SGK1 inhibitor on oxidative stress and cardiac damage in an isolated heart model of ischemia/reperfusion injury in rats

125 | May 29 2023

The study suggests that concomitant administration of gallic acid and the SGK1 gene inhibitor GSK650394 may have a more beneficial effect on cardiac ischemia/reperfusion injury than each drug alone. [Read the Full Post]

Administration of an LXR agonist promotes atherosclerotic lesion remodelling in murine inflammatory arthritis

175 | May 20 2023

The study shows that the LXR agonist T0901317 improves cholesterol efflux and atherosclerotic lesion regression in murine arthritis, potentially offering therapeutic benefits for patients with rheumatoid arthritis and atherosclerotic cardiovascular disease. [Read the Full Post]

Tyrosine Kinase Inhibitors Target B Lymphocytes

473 | May 20 2023

Protein kinase inhibitors previously used to treat ALK-positive lung cancer cells have shown potential in targeting LTK-positive B cells, providing new treatment options for autoimmune disorders and blood cancers. [Read the Full Post]

Celastrol inhibits necroptosis by attenuating the RIPK1/RIPK3/MLKL pathway and confers protection against acute pancreatitis in mice

301 | May 18 2023

Celastrol has been found to inhibit necroptosis by attenuating the phosphorylation of RIPK1, RIPK3, and MLKL and mitochondrial dysfunction in in vitro models, and in a mouse model of acute pancreatitis, it significantly reduced the severity of the disease and decreased the phosphorylation of MLKL in pancreatic tissues. [Read the Full Post]

An Umpolung Approach to Acyclic 1,4-Dicarbonyl Amides via Photoredox-Generated Carbamoyl Radicals

392 | May 15 2023

This passage describes a method for the generation and reaction of carbamoyl radicals from oxamate salts followed by reaction with electron-poor olefins, which enables the mild and mass-efficient formation of 1,4-dicarbonyl products, supported by ab initio calculations, and designed to be environmentally friendly. [Read the Full Post]

Allosteric inhibition of HSP70 in collaboration with STUB1 augments enzalutamide efficacy in antiandrogen resistant prostate tumor and patient-derived models

160 | May 13 2023

The study suggests that targeting HSP70 using small-molecule inhibitors, in combination with ARSI drugs, could be a promising approach to overcome resistance to ARSI in advanced prostate cancer. [Read the Full Post]

Mechanical Force Modulates Alveolar Bone Marrow Mesenchymal Cells Characteristics for Bone Remodeling during Orthodontic Tooth Movement through Lactate Production

101 | May 10 2023

This study suggests that lactate plays a crucial role in controlling bone remodeling-related cellular activities during orthodontic tooth movement, indicating its potential as a therapeutic target for improving orthodontic results. [Read the Full Post]

Re-evaluation of Brequinar sodium, a dihydroorotate dehydrogenase inhibitor

87 | May 09 2023

Brequinar sodium is a potent inhibitor of DHO-DH enzyme that induces myelosuppression by inhibiting DHO-DH in WBC and depleting plasma uridine, and has potential therapeutic applications in leukemia or inflammatory diseases. [Read the Full Post]

Determination and pharmacokinetics study of UK-5099 in mouse plasma by LC-MS/MS

101 | May 02 2023

The study developed and validated an HPLC-MS/MS method for determining UK-5099 levels in mice plasma after intraperitoneal administration, and reported the pharmacokinetic parameters of UK-5099 in mice, which will aid further study of its administration in animals and humans. [Read the Full Post]

Fk506 Inhibit liver regeneration in HOC model Rat

357 | Apr 30 2023

The study found that FK506 inhibits HOC activation and proliferation, ultimately blocking liver regeneration and highlighting the importance of understanding the role of lymphocytes in liver regeneration and the clinical use of FK506 in liver transplantation. [Read the Full Post]

Glucose induced-AKT/mTOR activation accelerates glycolysis and promotes cell survival in acute myeloid leukemia

235 | Apr 28 2023

The study found that glucose-induced AKT/mTOR activation promotes AML growth and inhibition of glycolysis may be a potential therapy strategy for AML. [Read the Full Post]

Positron Emission Tomography Imaging in Vasculitis

284 | Apr 27 2023

FDG-PET/CT is an important imaging tool in the diagnosis and therapeutic monitoring of vasculitides affecting large-sized and medium-sized vessels, and with advancements in newer generation scanners and development of novel tracers, it has shown significant potential in accurately assessing the full disease extent and detecting vascular infiltrates. [Read the Full Post]

The Multidrug Resistance Transporter P-glycoprotein Confers Resistance to Ferroptosis Inducers

236 | Apr 26 2023

The study investigates the interaction of small molecule ferroptosis inducers with ABC transporters, specifically P-glycoprotein and ABCG2, highlighting their potential role in limiting bioavailability and brain penetration of these inducers and predicting drug-drug interactions. [Read the Full Post]

Regulatory effects of trimetazidine in cardiac ischemia/reperfusion injury

123 | Apr 26 2023

MicroRNAs such as miR-21, miR-24, and miR-126, as well as trimetazidine, may have protective effects on myocardial ischemia/reperfusion injury by regulating gene expression and inducing key regulators such as AMPK, CSE/H2S, and miR-21. [Read the Full Post]

Emerging compounds and therapeutic strategies to treat infections from Trypanosoma brucei: an overhaul of the last 5-years patents

112 | Apr 26 2023

The review covers recent developments in the discovery of new therapeutic options for Human African Trypanosomiasis, including patents related to new antitrypanosomiasis agents, biological targets, vaccines, and formulations, as well as the selectivity and toxicity of natural and synthetic compounds against human cells. [Read the Full Post]

Auranofin Targeting the NDM-1 Beta-Lactamase: Computational Insights into the Electronic Configuration and Quasi-Tetrahedral Coordination of Gold Ions

316 | Apr 25 2023

Recent research has demonstrated that auranofin can restore penicillin and cephalosporin sensitivity in resistant bacterial strains via the inhibition of the NDM-1 beta-lactamase enzyme, accomplished through substituting gold for zinc in the enzyme's bimetallic core. [Read the Full Post]

Increased NLRP3 Inflammasome Activation and Pyroptosis in Patients With Multiple Sclerosis With Fingolimod Treatment Failure

109 | Apr 23 2023

Fingolimod's inhibition of the NLRP3 inflammasome in a subset of MS patients may be responsible for their response to treatment, as evidenced by the differential effect of fingolimod on the formation of an ASC oligomer in monocytes between responders and nonresponders. [Read the Full Post]

HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis

150 | Apr 22 2023

The study found that the oncoprotein HBXIP promotes breast cancer cell migration by blocking myosin-IIA assembly, and that the anti-hyperlipidemic drug bezafibrate (BZF) can inhibit PKCβII-mediated NMHC-IIA phosphorylation and suppress breast cancer metastasis both in vitro and in vivo. [Read the Full Post]

Adequacy of energy and macronutrients intake in differently active slovenian adolescents

545 | Apr 21 2023

The study found that a significant proportion of Slovenian adolescents are not meeting national recommendations for energy and macronutrient intake, and there were differences in energy/macronutrient intake between boys of different physical activity levels, highlighting the need for interventions to encourage healthy eating and physical activity behaviors. [Read the Full Post]

Perinatal Stressors as a Factor in Impairments to Nervous System Development and Functions: Review of In Vivo Models

439 | Apr 21 2023

This review evaluates different models of perinatal pathology and their relationship with psychoemotional stressors in understanding the impact of stress on the developing brain and behavior. [Read the Full Post]

Sitagliptin inhibits the survival, stemness and autophagy of glioma cells, and enhances temozolomide cytotoxicity

158 | Apr 21 2023

Sitagliptin shows promise as a potential antiglioma drug to overcome TMZ resistance and enhance the therapeutic efficacy of GBM treatment. [Read the Full Post]

PPAR agonists for the treatment of primary biliary cholangitis: Old and new tales

269 | Apr 20 2023

PPAR agonists are a promising new class of drugs for PBC treatment, especially for UDCA non-responders or intolerant patients, but further studies are needed to confirm their efficacy, safety, and long-term benefits. [Read the Full Post]

Insights into the mechanisms of triptolide nephrotoxicity through network pharmacology-based analysis and RNA-seq

451 | Apr 19 2023

The combination of network pharmacology and deep RNA-seq analysis provides valuable insights into the molecular mechanisms of TPL nephrotoxicity, identifying potential targets and signaling pathways for further investigation. [Read the Full Post]

Nogo-A Mediated Endoplasmic Reticulum Stress During Myocardial Ischemic-Reperfusion Injury in Diabetic Rats

78 | Apr 19 2023

The study suggests that Nogo-A mediated ER stress plays a major role in diabetic MI/R injury, and pathologically altered Nogo-A expression mediates diabetic MI/R injury, suggesting Nogo-A as a potential target for the treatment of diabetic MI/R injury in clinical settings. [Read the Full Post]

Targeting mitochondrial stress with SS31 prevents experimental abdominal aortic aneurysm: crosstalk with ER stress

89 | Apr 19 2023

The study demonstrates that inhibition of mitochondrial stress with SS31 limits AAA formation and increases survival through a reduction of vascular remodeling, inflammation, and ROS, and also supports the idea that the attenuation of ER stress contributes to the favorable response. [Read the Full Post]

Discovery, SAR, and Biological Evaluation of Non-inhibitory Chaperones of Glucocerebrosidase

105 | Apr 18 2023

High-throughput screening has identified ML198 and ML266 as chemical series that can facilitate translocation of mutant GCase to the lysosome without inhibiting the enzyme's activity, providing a potential starting point for the development of small molecule treatments for Gaucher disease. [Read the Full Post]

Chlorogenic acid, rutin, and quercetin from Lysimachia christinae alleviate triptolide-induced multi-organ injury in vivo by modulating immunity and AKT/mTOR signal pathway to inhibit ferroptosis and apoptosis

483 | Apr 18 2023

The study showed that a combination of organ-protective ingredients from Lysimachia christinae could protect against triptolide-induced multi-organ injury in vivo by activating the AKT/mTOR pathway and reducing cell death including ferroptosis and apoptosis inhibition. [Read the Full Post]

Small Molecule Inhibition of CPS1 Activity through an Allosteric Pocket

115 | Apr 17 2023

The discovery of small-molecule CPS1 inhibitors that bind to an allosteric pocket to block ATP hydrolysis is a promising development for targeting CPS1 overexpression in cancer cells and could provide valuable tools for researchers studying CPS1 cancer biology. [Read the Full Post]

Vitamin C promoted refractory organic contaminant elimination in the zero-valent iron/peracetic acid system: Efficiency, mechanism and effects of various parameters

218 | Apr 16 2023

This study proposes using vitamin C as a reducing agent to enhance the performance of the conventional ZVI/PAA system for the degradation of contaminants in water, leading to improved removal efficiency and potential for achieving a cleaner water environment. [Read the Full Post]

Trends in the Use of Oral Anticoagulants for Adults With Venous Thromboembolism in the US, 2010-2020

117 | Apr 13 2023

This retrospective cohort study using data from two US health insurance databases evaluated prescribing patterns of oral anticoagulants for patients with venous thromboembolism and identified clinical events that preceded treatment changes, highlighting the importance of identifying reasons for treatment modification for valid evidence on drug safety and effectiveness. [Read the Full Post]

[A convenient and time-saving method for primary culture of mature white adipocytes from mice]

273 | Apr 12 2023

The study established a simple, low-cost, and time-saving method for primary culture of mature white adipocytes from mice, enabling further functional studies. [Read the Full Post]

miR-223 Plays a Key Role in Obesogen-Enhanced Adipogenesis in Mesenchymal Stem Cells and in Transgenerational Obesity

195 | Apr 10 2023

The study found that exposure to the obesogen tributyltin (TBT) increased levels of the microRNA miR-223 in mesenchymal stem cells (MSCs), which may play a role in the development of obesity in male offspring of exposed pregnant mice through the PPARγ pathway. [Read the Full Post]

Lonafarnib improves cardiovascular function and survival in a mouse model of Hutchinson-Gilford progeria syndrome

221 | Apr 06 2023

This study reports the positive effects of lonafarnib on cardiovascular structure, properties, and function in a mouse model of progeria, leading to 100% survival of treated mice and improved arterial structure and function, while rapamycin did not improve outcomes. [Read the Full Post]

N-palmitoylethanolamide synergizes the antinociception of morphine and gabapentin in the formalin test in mice

112 | Apr 06 2023

The study investigated the synergistic antinociceptive effect of PEA in combination with MOR or GBP and found that PPARα and opioid receptors are involved in both interactions, suggesting potential use in treating inflammatory pain. [Read the Full Post]

The role of transforming growth factor-β2 in cigarette smoke-induced lung inflammation and injury

479 | Apr 06 2023

The study found that TGF-β2 attenuated CSE-induced IL-8 production in PBECs and alleviated lung inflammation/injury in CS-exposed mice through the Smad3 signaling pathway. [Read the Full Post]

Extracellularly Detectable Electrochemical Signals of Living Cells Originate from Metabolic Reactions

82 | Apr 05 2023

This study demonstrates that intracellular metabolic pathways generating ATP contribute to extracellularly detectable electrochemical signals in living cells, which can be amplified with metabolic activator cocktails and used to detect the effects of anticancer drugs and quantify senescence in mesenchymal stem cells. [Read the Full Post]

Pyruvate Dehydrogenase Inhibition Leads to Decreased Glycolysis, Increased Reliance on Gluconeogenesis and Alternative Sources of Acetyl-CoA in Acute Myeloid Leukemia

135 | Apr 05 2023

AML cells compensate for devimistat-mediated inhibition of PDH and glycolysis by activating alternative metabolic pathways such as gluconeogenesis, fatty acid oxidation, and non-glycolytic sources of acetyl-CoA, highlighting the need to explore strategies targeting these escape pathways to improve the efficacy of devimistat in AML. [Read the Full Post]

Structure-based mechanism and inhibition of cholesteryl ester transfer protein

137 | Apr 02 2023

Recent research on cholesteryl ester transfer proteins (CETP) has highlighted their role in regulating plasma cholesterol levels and their potential as a therapeutic target for ASCVD or dyslipidemia, with ongoing research focusing on the structural and mechanistic basis of CETP inhibition to guide the development of more effective anti-ASCVD therapeutics. [Read the Full Post]

Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent

299 | Mar 31 2023

The passage describes the pharmacokinetics of geldanamycin in mice and a dog and highlights the potential for acute hepatotoxic reactions, indicating a need for further pharmacological and therapeutic information before considering the drug for clinical development. [Read the Full Post]

Metabolic alterations and mitochondrial dysfunction underlie hepatocellular carcinoma cell death induced by a glycogen metabolic inhibitor

114 | Mar 31 2023

This study highlights the potential of targeting glycogen metabolism as a therapeutic strategy for HCC through inducing metabolic alterations and mitochondrial dysfunction. [Read the Full Post]

Identification of significant gene expression changes in multiple perturbation experiments using knockoffs

360 | Mar 30 2023

The approach described uses the model-X knockoffs framework and Deep Neural Networks to identify significant gene expression changes in multiple perturbation experiments, allowing for better understanding of underlying mechanisms of disease and identification of new drug targets. [Read the Full Post]

Phosphodiesterase 10A (PDE10A) as a novel target to suppress β-catenin and RAS signaling in epithelial ovarian cancer

110 | Mar 29 2023

PDE10A may be a promising target for ovarian cancer chemoprevention and treatment, as its inhibition leads to decreased ovarian cancer cell growth and induces cell cycle arrest and apoptosis through PKA and PKG signaling and decreased activation of oncogenic and inflammatory signaling pathways. [Read the Full Post]

Transcriptomics-Based Phenotypic Screening Supports Drug Discovery in Human Glioblastoma Cells

125 | Mar 29 2023

The study identifies novel druggable targets and potential combined drug, immunotherapy, and RNA vaccine approaches for treating glioblastoma, but effective pan-GBM drug treatment remains challenging due to extreme heterogeneity within drug-treated cells. [Read the Full Post]

The pro-inflammatory effect of triglyceride on human CD4+ T cells and experimental autoimmune uveitis

184 | Mar 28 2023

Aberrant lipid metabolism, specifically increased triglyceride levels, stimulates CD4+ T cells and promotes Th1 and Th17 cell differentiation in the pathogenesis of autoimmune uveitis, and inhibition of TAG generation using A922500 can ameliorate the disease severity by down-regulating Th17 cell response and promoting apoptosis-related protein expression. [Read the Full Post]

A nitric-oxide driven chemotactic nanomotor for enhanced immunotherapy of glioblastoma

163 | Mar 26 2023

The proposed chemotactic nanomotor loaded with brain endothelial cell targeting agent angiopep-2 and anti-tumor drug TLND, which uses ROS/iNOS as chemoattractants to induce the chemotactic behavior, has the potential to overcome major challenges of immunotherapy for glioblastoma and enhance the immune response against the tumor while preventing recurrence. [Read the Full Post]

Directly targeting ASC by lonidamine alleviates inflammasome-driven diseases

152 | Mar 26 2023

The study found that LND is a broad-spectrum inflammasome inhibitor that directly targets ASC and may have potential as a therapeutic agent for inflammasome-driven diseases in clinic. [Read the Full Post]

Cold acclimation and pioglitazone combined increase thermogenic capacity of BAT and WAT but this does not translate into higher energy expenditure

124 | Mar 25 2023

The study found that combining cold acclimation and pharmacological PPARγ activation leads to a synergistic increase in brown and beige adipocytes UCP1 content and thermogenic capacity, but does not innately lead to higher energy expenditure. [Read the Full Post]

Circulating follistatin concentrations in adolescent PCOS: Divergent effects of randomized treatments

121 | Mar 25 2023

This study found that oral contraceptives increase serum follistatin levels in non-obese adolescent girls with PCOS, which is associated with worsened markers of insulin resistance and changes in liver fat. [Read the Full Post]

Luteolin-7-O-rutinoside Protects RIN-5F Cells from High-Glucose-Induced Toxicity, Improves Glucose Homeostasis in L6 Myotubes, and Prevents Onset of Type 2 Diabetes

296 | Mar 24 2023

Lut-7-O-rutin has been found to have a protective effect on high-glucose-induced toxicity to RIN-5F cells and improve insulin secretion and glucose uptake through various molecular mechanisms. [Read the Full Post]

DEHP Decreases Steroidogenesis through the cAMP and ERK1/2 Signaling Pathways in FSH-Stimulated Human Granulosa Cells

223 | Mar 23 2023

DEHP inhibits the cAMP and ERK1/2 signaling pathways, leading to the inhibition of steroidogenesis in FSH-stimulated hCGC. [Read the Full Post]

Clonal hematopoiesis involving DNA damage response genes in patients undergoing lung transplantation is increased

97 | Mar 23 2023

The study found that clonal hematopoiesis (CH) in DNA damage response genes TP53, PPM1D, and ATM is highly prevalent in patients with severe lung disease undergoing lung transplantation and is associated with post-transplant outcomes including cytomegalovirus activation and mycophenolate intolerance. [Read the Full Post]

Dipotassium Glycyrrhizininate Improves Skin Wound Healing by Modulating Inflammatory Process

277 | Mar 22 2023

The study evaluated the anti-inflammatory effect of topical Dipotassium Glycyrrhizinate (DPG) on the healing of cutaneous wounds by secondary intention in an in vivo experimental model and found that DPG promotes skin wound healing through modulation of distinct mechanisms and signaling pathways, including anti-inflammatory ones. [Read the Full Post]

Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer

178 | Mar 21 2023

This study suggests that genetic variations in CYP17A1 and other androgen-related genes may help predict the efficacy and toxicity of abiraterone acetate treatment in advanced prostate cancer patients. [Read the Full Post]

Development and Optimisation of Inhalable EGCG Nano-Liposomes as a Potential Treatment for Pulmonary Arterial Hypertension by Implementation of the Design of Experiments Approach

410 | Mar 21 2023

The research developed an inhalable EGCG nano-liposome formulation with desirable properties and demonstrated its potential effectiveness in treating PAH by inhibiting the TGFβ pathway. [Read the Full Post]

Prospective role of 3βHSD1 in prostate cancer precision medicine

150 | Mar 20 2023

3βHSD1 is both a promising therapeutic target and a predictive biomarker for prostate cancer, with the development of novel inhibitors and a better understanding of its regulatory mechanisms providing new opportunities for disease management. [Read the Full Post]

Sterol O-Acyltransferase Inhibition Ameliorates High-Fat Diet-Induced Renal Fibrosis and Tertiary Lymphoid Tissue Maturation after Ischemic Reperfusion Injury

183 | Mar 17 2023

High-fat diet-induced renal tertiary lymphoid tissues and sustained inflammation in mice with ischemic reperfusion injury were found to be associated with sterol O-acyltransferase (SOAT) 1-dependent cholesteryl ester accumulation, and SOAT1 inhibition was found to attenuate TLT formation and renal inflammation, suggesting its potential as a therapeutic target for CKD prevention and treatment. [Read the Full Post]

Blocking Cholesterol Metabolism with Tumor-Penetrable Nanovesicles to Improve Photodynamic Cancer Immunotherapy

298 | Mar 17 2023

Researchers have designed matrix metalloproteinase-2-sensitive tumor-penetrable nanovesicles that can regulate cholesterol metabolism to enhance photodynamic cancer immunotherapy by reinvigorating the functions of CD8+ T cells and suppressing the migration of tumor cells. [Read the Full Post]

The effect of lipid-lowering therapies on the pro-inflammatory and anti-inflammatory properties of vascular endothelial cells

139 | Mar 16 2023

The study found that both statins, particularly rosuvastatin, had a stronger anti-inflammatory effect than ezetimibe in endothelial cells damaged by 25-hydroxycholesterol. [Read the Full Post]

Paclitaxel and docetaxel resistance in prostate cancer: Molecular mechanisms and possible therapeutic strategies

137 | Mar 15 2023

This review highlights the mechanisms of paclitaxel and docetaxel resistance in prostate cancer and discusses the potential of phytochemicals and nanostructures for reversing drug resistance. [Read the Full Post]

Significance of Basal Membrane Permeability of Epithelial Cells in Predicting Intestinal Drug Absorption

164 | Mar 15 2023

The study showed that assessing the permeability of A and B membranes separately and accounting for the intracellular drug concentration can improve the accuracy of predicting drug absorption in the gastrointestinal tract and understanding the role of transporters and enzymes. [Read the Full Post]

Mechanistic in vitro studies indicate that the clinical drug-drug interactions between protease inhibitors and rosuvastatin are driven by inhibition of intestinal BCRP and hepatic OATP1B1 with minimal contribution from OATP1B3, NTCP and OAT3

132 | Mar 15 2023

This passage describes the use of a mechanistic static model to reconcile the disconnect between predicted and clinically observed area under the plasma concentration-time curve ratio (AUCR) of rosuvastatin due to drug-drug interaction (DDI) with atazanavir, by evaluating the inhibitory effects of atazanavir and other protease inhibitors on additional transporters, and integrating a combined hepatic transport component into the model. [Read the Full Post]

Prophylactic Agents for Preventing Cardiotoxicity Induced Following Anticancer Agents: A Systematic Review and Meta-Analysis of Clinical Trials

153 | Mar 14 2023

This meta-analysis showed that prophylactic treatment with cardio-protective drugs can protect the left ventricular ejection fraction (LVEF) and prevent EF drop in patients undergoing chemotherapy with anthracyclines. [Read the Full Post]

Treating linear porokeratosis with topical lovastatin/cholesterol cream

243 | Mar 14 2023

Linear porokeratosis is a rare skin condition characterized by unilateral linear lesions that follow the lines of Blaschko and is currently treated with therapies aimed at restoring the mevalonate biosynthesis pathway and keratinocyte cholesterol availability, such as compounded 2% lovastatin/2% cholesterol cream. [Read the Full Post]

A new series of hydrazones as small-molecule aldose reductase inhibitors

224 | Mar 13 2023

The study reports the design, synthesis, and evaluation of tetrazole-hydrazone hybrids as aldose reductase inhibitors, identifying compound 4 as the most potent and safe inhibitor for further in vivo studies. [Read the Full Post]

Effect of Pre-Meal Metformin With or Without an Acute Exercise Bout on Postprandial Lipemic and Glycemic Responses in Metabolic Syndrome Patients: A Randomized, Open Label, Crossover Study

398 | Mar 12 2023

Pre-meal metformin administration 30 minutes prior to the meal has favorable effects on postprandial total cholesterol and LDL-cholesterol levels compared to its administration with the meal, and the addition of one exercise bout only improves postprandial glycemia and insulinemia in metabolic syndrome patients. [Read the Full Post]

Chitosan-Enclosed Menadione Sodium Bisulfite as an Environmentally Friendly Alternative to Enhance Biostimulant Properties against Drought

174 | Mar 11 2023

The use of nanoencapsulation to deliver menadione sodium bisulfite has been shown to improve its protective properties against water deficit stress and reduce the need for continuous retreatment, highlighting the potential of nanotechnology to enhance the performance of biostimulants in agriculture. [Read the Full Post]

Impacts of Statin Therapy Strategies on Incidence of Ischemic Cerebrovascular Events in Patients With Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Bayesian Network Meta-Analysis

158 | Mar 08 2023

The Bayesian network meta-analysis and systematic review suggest that statins can significantly improve functional prognosis and reduce the incidence of ischemic cerebrovascular events in patients with aSAH, with pravastatin (40 mg/d) being the most effective type of statin. [Read the Full Post]

Assessment of the regenerative potential of macro-porous chitosan-calcium simvastatin scaffolds on bone cells

301 | Mar 08 2023

The study evaluated the bioactive potential of a macro-porous chitosan scaffold incorporated with calcium hydroxide and functionalized with bioactive doses of simvastatin for bone tissue regeneration, demonstrating increased bioactivity and promising potential. [Read the Full Post]

Chemotherapeutic Activity of Pitavastatin in Vincristine Resistant B-Cell Acute Lymphoblastic Leukemia

230 | Mar 07 2023

The study suggests that pitavastatin may have potential as a repurposed chemotherapeutic agent for vincristine-resistant B-cell acute lymphoblastic leukemia. [Read the Full Post]

Effect of Disulfiram on the Reproductive Capacity of Female Mice

289 | Mar 03 2023

Disulfiram (DSF) has been found to increase ovulation rate, enhance antioxidant capacity of oocytes, and promote successful pregnancy in mice by regulating gene expression related to angiogenesis, follicular development, ovulation, and antioxidants, however, more research is needed to determine if these results can be translated to humans and the safety of using DSF during pregnancy. [Read the Full Post]

Medications for the Treatment of Alcohol Dependence-Current State of Knowledge and Future Perspectives from a Public Health Perspective

339 | Mar 03 2023

The treatment of alcohol dependence requires a multi-disciplinary approach, combining psychotherapy with medications, and more research is needed to find new and effective treatments for this complex condition. [Read the Full Post]

13-cis-retinoic acid (NSC 122758) in the treatment of children with metastatic neuroblastoma unresponsive to conventional chemotherapy: report from the Childrens Cancer Study Group

236 | Mar 02 2023

The study conducted by the Children's Cancer Study Group on 13-cis-retinoic acid in children with advanced neuroblastoma showed no significant activity and the drug was not effective in treating the condition. [Read the Full Post]

CNKSR2, a downstream mediator of retinoic acid signaling, modulates the Ras/Raf/MEK pathway to regulate patterning and invagination of the chick forebrain roof plate

114 | Mar 02 2023

The study found that CNKSR2, a novel mediator of retinoic acid (RA) signaling, plays a crucial role in the morphogenesis of the avian forebrain by modulating the Ras/Raf/MEK signaling, leading to proper invagination, cell proliferation, and patterning of the roof plate for the formation of the cerebral hemispheres. [Read the Full Post]

Cost-effectiveness of targeted screening for non-valvular atrial fibrillation in the United Kingdom in older patients using digital approaches

172 | Feb 27 2023

Screening for non-valvular atrial fibrillation in patients aged 75 or older in the UK is cost-effective and potentially cost-saving, with handheld digital devices such as Zenicor, pulse palpation, and KardiaMobile, and targeted screening predictive algorithms found to be the dominant options compared to no screening. [Read the Full Post]

DOAC compared with warfarin for VTE in patients with obesity: a retrospective cohort study conducted through the VENUS network

116 | Feb 27 2023

The study found that DOACs were not inferior to warfarin in terms of VTE recurrence in obese patients and were associated with a lower major bleeding rate. [Read the Full Post]

Aminopeptidases in Cancer, Biology and Prospects for Pharmacological Intervention

175 | Feb 24 2023

Aminopeptidases play a crucial role in cellular processes and functions, including metabolism, signaling, angiogenesis, and immunology, and their overexpression in tumor cells can facilitate rapid proliferation, leading to potential use as a targeted approach for new oncological treatments. [Read the Full Post]

A randomised evaluation of low-dose cytosine arabinoside (ara-C) plus tosedostat versus low-dose ara-C in older patients with acute myeloid leukaemia: results of the LI-1 trial

183 | Feb 24 2023

The "Pick-a-Winner" LI-1 trial of 243 older acute myeloid leukemia (AML) patients who were not suitable for intensive treatment showed no statistically significant improvement in complete remission, overall response, or overall survival with the addition of tosedostat, a selective oral aminopeptidase inhibitor, to low-dose cytosine arabinoside. [Read the Full Post]

Association between Quality of Life and Visual Acuity in a Randomized Clinical Trial of Patients with Uveitis Taking Antimetabolites

121 | Feb 23 2023

The study evaluated the association between changes in visual acuity and quality of life among patients with non-infectious uveitis taking antimetabolites, and found that changes in visual acuity were significantly correlated with changes in quality of life, and the treatment group was not significantly associated with any quality of life measure. [Read the Full Post]

Influence of SLCO1B1 Polymorphisms on the Pharmacokinetics of Mycophenolic Acid in Renal Transplant Recipients

154 | Feb 23 2023

This study found a correlation between 4 single nucleotide polymorphisms (SNPs) and the pharmacokinetics of mycophenolic acid (MPA) in renal transplant recipients, with the most relevant SNP being rs4149036 located in SLCO1B1, which had a stronger influence on older, male, or high-albumin recipients. [Read the Full Post]

Clinical effect of intravenous calcitriol administration on secondary hyperparathyroidism. A double-blind study among 4 doses

121 | Feb 22 2023

The study determined the appropriate initial dose of intravenous calcitriol for reducing PTH levels in patients with uremic secondary hyperparathyroidism (2HPT) to be 1 microg per dialysis session, with a clear dose-dependent effect seen on PTH reduction. [Read the Full Post]

Fibroblast Growth Factor 23 Exacerbates Cardiac Fibrosis in Deoxycorticosterone Acetate-Salt Mice With Hypertension

118 | Feb 21 2023

Continuous intravenous administration of fibroblast growth factor 23 in a mouse model with mild chronic kidney disease and hypertension leads to heart failure with preserved ejection fraction, exacerbated myocardial fibrosis, and a decrease in Cyp27b1 expression, which is mitigated by calcitriol treatment that improves diastolic function via inhibiting transforming growth factor-β signaling, independently of the levels of FGF23. [Read the Full Post]

Therapeutic treatment with phosphodiesterase-4 inhibitors alleviates kidney injury and renal fibrosis by increasing MMP-9 in a doxorubicin-induced nephrotoxicity mouse model

103 | Feb 20 2023

PDE-4 inhibitors rolipram and roflumilast showed beneficial effects in preserving glomerular filtration barrier function, reducing inflammation, and decreasing renal fibrosis in a doxorubicin-induced nephrotic syndrome model, with roflumilast having better effects in reducing glomerular and tubular lesions and MMP9 activity in renal tissue at later stages. [Read the Full Post]

Levosimendan increases the phosphorylation state of phospholamban in the isolated human atrium

108 | Feb 20 2023

Levosimendan increased force of contraction in the mouse left atrial preparations in the presence of rolipram and had positive inotropic and chronotropic effects in both mouse and human atrial preparations, with the positive inotropic effect being explained by phosphodiesterase III inhibition leading to phospholamban phosphorylation in the human atrium. [Read the Full Post]

Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise

831 | Feb 19 2023

Liver cancer treatment options depend on the progression stage of the disease and may include surgery, ablation and radiotherapy, first-line drugs and immunotherapy, and second-line chemotherapeutic drugs, while natural compounds like resveratrol, curcumin and diallyl sulfide are emerging as promising anticancer agents to manage liver cancer. [Read the Full Post]

Inclusion complex of ketoconazole and p-sulfonic acid calix[6]arene improves antileishmanial activity and selectivity against Leishmania amazonensis and Leishmania infantum

129 | Feb 18 2023

An inclusion complex (IC6HKTZ) of ketoconazole and p-sulfonic acid calix[6]arene (CX6SO3H) was prepared to improve solubility and efficacy of ketoconazole against Leishmania amazonensis and Leishmania infantum, and results showed a 95-fold solubility enhancement and improved antileishmanial activities. [Read the Full Post]

Sample stability and heparin interference in ionized calcium and ionized magnesium measurements in horses using the Stat Profile Prime Plus co-oximetry electrolyte analyzer

263 | Feb 17 2023

Stored samples at 4°C can be used to determine iCa and iMg concentrations up to 7 days after collection in horses, but heparin interference should be considered when using homemade heparin syringes and other metabolites are stable for only 8 hours. [Read the Full Post]

Phytochemical Analysis, Antifungal, and Antioxidant Properties of Two Herbs ( Tristemma mauritianum and Crassocephalum bougheyanum) and One Tree ( Lavigeria macrocarpa) Species

222 | Feb 17 2023

Tristemma mauritianum, Crassocephalum bougheyanum, and Lavigeria macrocarpa showed promising antifungal and antioxidant properties due to high phenolic, tannin, and flavonoid content, with T. mauritianum displaying the highest antifungal and antioxidant activities and a synergistic effect with ketoconazole against clinical resistant Candida isolates. [Read the Full Post]

Synthesis of Benzimidazole-1,2,4-triazole Derivatives as Potential Antifungal Agents Targeting 14α-Demethylase

114 | Feb 16 2023

Benzimidazole-1,2,4-triazole derivatives were synthesized and screened for their antifungal activity against C. albicans, C. glabrata, C. krusei, and C. parapsilopsis, with three compounds (6b, 6i, and 6j) showing higher antifungal activity than voriconazole and fluconazole, and potential for use as a new fungicidal lead targeting 14α-demethylase with effects on the L929 cell line and C. glabrata cells evaluated. [Read the Full Post]

Pulmonary cryptococcosis after immunomodulator treatment in patients with Crohn's disease: Three case reports

98 | Feb 16 2023

Three patients with Crohn's disease developed pulmonary cryptococcosis after receiving immunomodulatory treatment and were successfully treated with fluconazole; increased incidence of this opportunistic infection highlights the need for clinical vigilance and early identification for standardized treatment. [Read the Full Post]

Anti-inflammatory effects of first-line anti-arthritic drugs on T-cell activation

154 | Feb 13 2023

Anti-arthritic drugs can inhibit pro-inflammatory cytokines and potentially stimulate a Th2 response to inhibit the progression of the immune response, as seen in the study examining their in vitro effects on early stages of T-cell activation. [Read the Full Post]

Effect of Gubenyiliu formula II and its disassembled prescriptions on cell autophagy in breast cancer through PI3K/AKT/mTOR pathway

518 | Feb 12 2023

This study confirmed that GYII can effectively treat breast cancer by inhibiting the PI3K/AKT/mTOR signaling pathway-mediated autophagy, while QX and FZ have different effects on tumor growth and metastasis. [Read the Full Post]

Specific gene module pair-based target identification and drug discovery

700 | Feb 12 2023

A novel method called "gene module pair-based target identification (GMPTI)" was developed to predict the targets of new compounds using consensus gene modules extracted from transcriptional profiles induced by perturbagens of known targets, resulting in the discovery of novel inhibitors for three PI3K pathway proteins. [Read the Full Post]

[TRANSLATED ARTICLE] Biological and immunosuppressive medications in pregnancy, breastfeeding and fertility in immune mediated diseases

232 | Feb 12 2023

The objective of this review was to gather available evidence on drugs used in immune-mediated inflammatory diseases during pregnancy and lactation, their impact on fertility, and to provide advice on family planning based on analyzed studies until April 2020. [Read the Full Post]

Gancao Nourishing-Yin decoction combined with methotrexate in treatment of aging CIA mice: a study based on DIA proteomic analysis

393 | Feb 07 2023

Gancao Nourishing-Yin decoction (GCNY) added to methotrexate (MTX) showed better effects in treating elderly rheumatoid arthritis (ERA) mice model compared to either treatment alone, as seen through improved joint damage, decreased inflammation, and regulation of metabolism-related pathways, and ELISAs confirmed improved folic acid levels and anti-folate resistance pathways. [Read the Full Post]

Five-year cardiovascular event risk in early rheumatoid arthritis patients who received treat-to-target management: a case-control study

343 | Feb 07 2023

The study found that ERA patients managed using a treat-to-target strategy had a similar incidence of cardiovascular events compared to a CV risk factor-matched non-RA population, while a historical RA cohort receiving routine care had a significantly higher incidence. [Read the Full Post]

The effect of cladribine on immunoglobulin levels compared to B cell targeting therapies in multiple sclerosis

242 | Feb 05 2023

Cladribine therapy for RRMS does not significantly reduce immunoglobulin subset levels, unlike ocrelizumab and natalizumab which showed a statistically significant reduction in IgG and IgM levels. [Read the Full Post]

Real-world experience of cladribine treatment in relapsing-remitting multiple sclerosis: A Danish nationwide study

252 | Feb 05 2023

A registry-based observational cohort study of all Danish patients starting cladribine tablets for relapsing multiple sclerosis showed the treatment was safe with a significant reduction in annualized relapse rate, but a longer follow-up period is needed to fully assess the long-term benefit and risk. [Read the Full Post]

Effectiveness of different treatment regimens on patients with COVID-19, hospitalized in Sanandaj hospitals: a retrospective cohort study

150 | Feb 03 2023

The study found that the drug regimen 2 (Interferons (ReciGen/Ziphron) or Interferon Vectra (lopinavir/ritonavir)) increased the days of hospitalization and hospitalization in ICU, while other drug regimens had no significant effect on mortality, use of a ventilator, or reducing mortality compared to the others. [Read the Full Post]

Awareness on current status of usage of ritonavir in the management of covid among dental students

236 | Feb 03 2023

A survey of 100 dental students in Chennai showed that postgraduate students had greater knowledge of the current use of Ritonavir in the management of COVID-19, but the study highlights the need for regular education and training programs for all healthcare workers on COVID-19 infection control procedures. [Read the Full Post]

In Vitro Characterization of 177Lu-DOTA-M5A Anti-Carcinoembryonic Antigen Humanized Antibody and HSP90 Inhibition for Potentiated Radioimmunotherapy of Colorectal Cancer

149 | Feb 02 2023

The combination therapy of 177Lu-radiolabeled anti-CEA hT84.66-M5A mAb (M5A) and the heat shock protein 90 inhibitor onalespib showed enhanced therapeutic effects over individual monotherapies for the potential treatment of colorectal cancer. [Read the Full Post]

Upregulation of TGF-β-induced HSP27 by HSP90 inhibitors in osteoblasts

161 | Feb 01 2023

The study found that HSP90 inhibitors increased TGF-β-induced HSP27 expression in mouse osteoblastic MC3T3-E1 cells through the SAPK/JNK pathway. [Read the Full Post]

Rescue of Misfolded Organic Cation Transporter 3 Variants

245 | Jan 27 2023

Thomas J F Angenoorth et al. found that folding-deficient SLC22 transporter variants, in particular those of OCT3, were amenable to rescue by chaperones. [Read the Full Post]

Heat shock protein 90 inhibitors induce cell differentiation via the ubiquitin-dependent aurora kinase A degradation in a MPLW515L mouse model of primary myelofibrosis

157 | Jan 27 2023

Fuping Wang et al. demonstrated that combined therapy showed superior activity in acute megakaryocytic leukemia mouse model than single therapy. [Read the Full Post]

Impact of Results of TTF-1 Immunostaining on Efficacy of Platinum-Doublet Chemotherapy in Japanese Patients with Nonsquamous Non-Small-Cell Lung Cancer

413 | Jan 26 2023

Akira Nakao et al. thought that the positivity of TTF-1 immunostaining in tumors could be a predominant prognostic marker for patients who had advanced nonsq NSCLC. [Read the Full Post]

Exonuclease 1 genetic variant is associated with clinical outcomes of pemetrexed chemotherapy in lung adenocarcinoma

433 | Jan 26 2023

Mi Jeong Hong et al. thought that two SNPs in miRNA binding sites, especially EXO1 rs1047840G>A, were associated with the chemotherapy response and survival outcome in lung adenocarcinoma patients treated with pemetrexed. [Read the Full Post]

A Novel Cuproptosis-Related Prognostic Model and the Hub Gene FDX1 Predict the Prognosis and Correlate with Immune Infiltration in Clear Cell Renal Cell Carcinoma

230 | Jan 07 2023

Kenan Zhang et al. constructed a CRGs prognostic model and revealed that FDX1 could serve as a prognostic biomarker and predict therapeutic response in ccRCC. [Read the Full Post]

Identification of cuproptosis-related long non-coding ribonucleic acid signature as a novel prognosis model for colon cancer

229 | Jan 07 2023

Rong Xu et al. found that inhibition of AL512306.3 and ZEB1-AS1 significantly suppressed the cell proliferation in colon cancer cells. [Read the Full Post]

Factors contributing to the utilization of robotic colorectal surgery: a systematic review and meta-analysis

131 | Dec 17 2022

Dana M Hayden et al. identifies nonclinical disparities in access to robotics that should be addressed to provide more equitable access to innovations in colorectal surgery. [Read the Full Post]

Fifty Shades of Scandium: Comparative Study of PET Capabilities Using Sc-43 and Sc-44 with Respect to Conventional Clinical Radionuclides

184 | Dec 11 2022

Thiago V M Lima et al. thought that accurate quantitative scandium-43/44 PET/CT was achievable in commercial devices. [Read the Full Post]

Inhibition of ACLY Leads to Suppression of Osteoclast Differentiation and Function Via Regulation of Histone Acetylation

98 | Dec 09 2022

Qian Guo et al. proved that inhibition of ATP-citrate lyase led to suppression of osteoclast differentiation and function via regulation of histone acetylation. [Read the Full Post]

Structure-based virtual screening for identification of potential non-steroidal LXR modulators against neurodegenerative conditions

230 | Dec 04 2022

Sonam Deshwal et al. found that potential non-steroidal LXR modulators that appeared to be effective against various neurodegenerative conditions involving perturbed cholesterol and lipid homeostasis. [Read the Full Post]

M2 Macrophage-Derived Exosomal Ferritin Heavy Chain Promotes Colon Cancer Cell Proliferation

192 | Dec 02 2022

Zilu Cui et al. found that purified exosomes from M2 macrophages could deliver FTH1 into colon cancer cells and promote cell proliferation. [Read the Full Post]

Effect of concomitant use of pitavastatin with neoadjuvant chemotherapy protocols in breast cancer patients: A randomized controlled clinical trial

327 | Nov 21 2022

Samar A Dewidar et al. thought that concomitant use of pitavastatin with standard neoadjuvant chemotherapy protocols might improve neoadjuvant chemotherapy responses in patients with breast cancer. [Read the Full Post]

Multifunctional Polydopamine-Based Nanoparticles for Dual-Mode Imaging Guided Targeted Therapy of Lupus Nephritis

259 | Nov 16 2022

Mifang Li et al. found that Nec-1/PDA@Pt-Fe3O4 nanocarrier exhibited good biocompatibility. [Read the Full Post]

Dual Delivery of Cyclosporin A and Etodolac Using Polymeric Nanocapsules in a Rabbit Eye Model: Ocular Biodistribution and Pharmacokinetic Study

158 | Nov 11 2022

Syed Nazrin Ruhina Rahman et al. thought that the biodistribution and pharmacokinetic data might help and strengthen their understanding of synergetic anti-inflammatory activity of CsA and Edc from nanocapsules after its ocular topical application for managing keratoconjunctivitis sicca. [Read the Full Post]

Phase 1 multicenter study of the HSP90 inhibitor SNX-5422 plus carboplatin and paclitaxel in patients with lung cancers

0 | Nov 10 2022

Martin Gutierrez et al. found that the triplet combination of SNX-5422, carboplatin and paclitaxel followed by maintenance SNX-5422 therapy was well-tolerated and showed anti-tumor activity [Read the Full Post]

Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells

0 | Nov 09 2022

Ria Goswami et al. found that an orally bioavailable Hsp90 inhibitor, SNX-5422, currently in clinical trials as an anti-cancer therapeutic, inhibited SARS-CoV-2 replication in vitro at a high selectivity index. [Read the Full Post]

Enterovirus A71 utilizes host cell lipid β-oxidation to promote its replication

128 | Nov 06 2022

Xiuwen Yang et al. found that it was the β-oxidation of lipid that plays a core role, not ER stress, which was only a concomitant change without restrictive effect, on virus replication. [Read the Full Post]

Inhibiting PP2A Upregulates B7-H3 Expression and Potentially Increases the Sensitivity of Malignant Meningiomas to Immunotherapy by Proteomics

237 | Nov 02 2022

Boyi Hu et al. found that the PP2A inhibitor LB-100 increased the phosphorylation of STAT1 and B7-H3 expression, which could increase the sensitivity of malignant meningiomas to B7-H3 targeted immunotherapy. [Read the Full Post]

Ganetespib selectively sensitizes cancer cells for proximal and distal spread-out Bragg peak proton irradiation

347 | Oct 30 2022

Simon Deycmar et al. provided additional experimental data on cellular response and a rational for future combinatorial approaches with proton radiotherapy. [Read the Full Post]

Hsp90 Inhibitor STA9090 induced VPS35 related extracellular vesicle release and metastasis in hepatocellular carcinoma

194 | Oct 29 2022

Wenchong Tan et al. found that therapeutic strategy to inhibit the metastasis of HCC caused by N-terminal Hsp90 inhibitor induced extracellular vesicles. [Read the Full Post]

Norepinephrine and dopamine contribute to distinct repetitive behaviors induced by novel odorant stress in male and female mice

84 | Oct 22 2022

Daniel J Lustberg et al. established a simple method for repeated assessment of stress-induced repetitive behaviors in mice. [Read the Full Post]

Norepinephrine and dopamine contribute to distinct repetitive behaviors induced by novel odorant stress in male and female mice

0 | Oct 22 2022

Daniel J Lustberg et al. established a simple method for repeated assessment of stress-induced repetitive behaviors in mice. [Read the Full Post]

UC-MSCs promote frozen-thawed ovaries angiogenesis via activation of the Wnt/β-catenin pathway in vitro ovarian culture system

331 | Oct 16 2022

Wenjuan Xu et al. showed the beneficial effects of UC-MSCs on thawed ovaries and explored a potential mechanism inducing angiogenesis. [Read the Full Post]

Luteinizing Hormone Receptor Promotes Angiogenesis In Ovarian Endothelial Cells of Macaca fascicularis and Homo sapiens

145 | Oct 15 2022

Merete Lund et al. found that the LH surge may directly activate ovarian endothelial cells to stimulate angiogenesis of the ovulatory follicle. [Read the Full Post]

Subtype and site specific-induced metabolic vulnerabilities in prostate cancer

156 | Sep 27 2022

Federica Mossa et al. thought that castration-resistant ARPC and AVPC exhibited different metabolic dependencies, which could further undergo metabolic reprogramming in bone. [Read the Full Post]

GW4064 Alters Gut Microbiota Composition and Counteracts Autism-Associated Behaviors in BTBR T+tf/J Mice

224 | Sep 21 2022

Jiayin Liu et al. suggested that GW4064 supplementation might prove a potential strategy for improving ASD symptoms. [Read the Full Post]

Arylsulfatase I is a prognostic biomarker for head and neck squamous cell carcinoma and Pan-cancer

128 | Sep 20 2022

Yiming Shen et al. showed that ARSI was highly involved in tumor cell escape and inflammatory responses. [Read the Full Post]

Identification of NAPRT Inhibitors with Anti-Cancer Properties by In Silico Drug Discovery

252 | Sep 20 2022

Moustafa S Ghanem et al. showed comparable anti-cancer activity to 2-HNA and improved predicted aqueous solubility, in addition to demonstrating favorable drug-like profiles. [Read the Full Post]

[Correlation between low expression of Hsp90 protein in keratinocytes and the number of small extracellular vesicles and its potential clinical significance]

332 | Sep 17 2022

Jun Chen et al. found that the secretion of sEVs in HaCaT cells. sEVs may be involved in the transfer of molecules between epithelial cells and immune cells. [Read the Full Post]

Identification of potential immunotherapy biomarkers for breast cancer by bioinformatics analysis

340 | Sep 16 2022

Yao Song et al. found that CD24, MMP1, SDC1, and SPP1 were potentially associated with five immune cell types infiltration (CD8+ T cells, CD4+ T cells, neutrophils, macrophages,and dendritic cells) by TIMER. [Read the Full Post]

Non-small cell lung cancer with EGFR exon 20 insertion mutation: a systematic literature review and meta-analysis of patient outcomes

289 | Sep 05 2022

Christina Soeun Kwon et al. found EGFR exon 20 insertion mutations as the availability of new targeted treatments might offer additional therapeutic options to these patients. [Read the Full Post]

A Low Membrane Hsp70 Expression in Tumor Cells With Impaired Lactate Metabolism Mediates Radiosensitization by NVP-AUY922

270 | Sep 05 2022

Melissa Schwab et al. found that the membrane Hsp70 density, but not cytosolic HSP levels determined the radiosensitizing effect of the Hsp90 inhibitor NVP-AUY922 in LDH-/- cells. [Read the Full Post]

Chronic AMPK Activation Reduces the Expression and Alters Distribution of Synaptic Proteins in Neuronal SH-SY5Y Cells

176 | Aug 29 2022

Alex J T Yang et al. suggested that chronic AMPK activation impacted synaptic protein content and reduced neurite protein abundance and distribution. [Read the Full Post]

[The Effect of KRAS on Proliferation and Apoptosis of T-ALL Cell Lines]

88 | Aug 24 2022

Zi-Yang Liu et al. thought that the KRAS protein was vital for the progression of the T-ALL cells in vitro, it was a potential therapeutic target for T-ALL patients. [Read the Full Post]

Expression, purification, and kinetic characterization of the human strep-IDO1

180 | Aug 19 2022

Dilizhatai Saimi et al. thought that purified human strep-IDO1 using the protocol described in the study could be used for further biochemical and structural analyses, which might facilitate functional research and further drug screening study on IDO1. [Read the Full Post]

IDO1 Inhibition Reduces Immune Cell Exclusion Through Inducing Cell Migration While PD-1 Blockage Increases IL-6 and -8 Secretion From T Cells in Head and Neck Cancer

148 | Aug 19 2022

Meri Sieviläinen et al. revealed the subpopulation of lymphocytes responsible for the increases in specific serum cytokines after ICI treatment. [Read the Full Post]

Repeated exposure to sevoflurane in neonatal rats impairs cognition in adulthood via the PKA-CREB-BDNF signaling pathway

155 | Aug 08 2022

Jili Zhao et al. found that PKA-CREB-BDNF signaling served an important role in the cognitive decline caused by neonatal exposure to Sev. [Read the Full Post]

Casein Kinase 2 Signaling in White Matter Stroke

373 | Aug 04 2022

Hung Nguyen et al. thought that miRNA regulation might be one of the protective actions of CX-4945 against WM ischemic injury. [Read the Full Post]

Anti-adipogenic and Pro-lipolytic Effects on 3T3-L1 Preadipocytes by CX-4945, an Inhibitor of Casein Kinase 2

365 | Aug 04 2022

Anil Kumar Yadav et al. found that CX-4945 had strong anti-adipogenic and pro-lipolytic effects on differentiating and differentiated 3T3-L1 cells, mediated by control of the expression and phosphorylation levels of CK2, C/EBP-α, PPAR-γ, FAS, ACC, perilipin A, AMPK, LKB-1, ERK-1/2, and HSL. [Read the Full Post]

Upregulation of FOXO1 contributes to lipopolysaccharide-induced pulmonary endothelial injury by induction of autophagy

94 | Aug 02 2022

Ying Zhao et al. demonstrated that FOXO1 upregulation was an important contributor to LPS-induced autophagy in pulmonary VE cells. [Read the Full Post]

Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy

469 | Jul 30 2022

Pincha Devage Sameera Madushan Fernando et al. found that hesperidin showed therapeutic potential against PM2.5-induced skin damage by mitigating excessive ROS accumulation, autophagy, and apoptosis. [Read the Full Post]

Metastatic pulmonary carcinoids with EML4-ALK fusion response to ALK inhibitors: two case reports and review of literature

368 | Jul 18 2022

Xi Lei et al. recommend alectinib for the first-line treatment of metastatic PC with EML4-ALK fusion. [Read the Full Post]

Multicenter phase II, double-blind placebo-controlled trial of maintenance ixazomib after allogeneic transplantation for high-risk multiple myeloma: Results of the BMT CTN 1302 Trial

332 | Jul 17 2022

Qaiser Bashir et al. found the safety and durable disease control with allo-HCT in high-risk myeloma patients. [Read the Full Post]

Combination mTOR and SHP2 inhibitor treatment of lymphatic malformation endothelial cells

105 | Jun 13 2022

Jennifer K Wolter et al. suggested that combination treatment targeting the PI3K and RAS signaling pathways might result in effective treatment of LMs of the head and neck. [Read the Full Post]

ARHGAP9 inhibits colorectal cancer cell proliferation, invasion and EMT via targeting PI3K/AKT/mTOR signaling pathway

709 | Jun 10 2022

Jufeng Sun et al. thought that ARHGAP9 inhibited the malignant phenotypes of CRC cells via interdicting PI3K/AKT/mTOR signaling pathway. [Read the Full Post]

Lonafarnib Inhibits Farnesyltransferase via Suppressing ERK Signaling Pathway to Prevent Osteoclastogenesis in Titanium Particle-Induced Osteolysis

226 | Jun 07 2022

Linke Huang et al. found that Lon was a promising treatment option for osteoclast-related osteolysis diseases including periprosthetic osteolysis by targeted inhibition of FTase through suppressing ERK signaling. [Read the Full Post]

Acid-Responsive Micelles Releasing Cinnamaldehyde Enhance RSL3-Induced Ferroptosis in Tumor Cells

221 | Jun 06 2022

Ziliang Yan et al. confirmed that RSL3@PCA has excellent inhibition of tumor growth without significant toxicity to normal cells and tissues and still has a good therapeutic effect on tumor cells that are resistant to conventional chemotherapy drugs. [Read the Full Post]

The Effects of PI3K/Akt/mTOR Signaling Pathway Inhibitors on the Expression of Immune Checkpoint Ligands in Acute Myeloid Leukemia Cell Line

284 | May 04 2022

Saeid Taghiloo et al. found that combinational treatment approaches to block these pathways might be a promising and novel therapeutic strategy for AML patients via interfering in immune escape mechanisms. [Read the Full Post]

Inhibition of DDX3 and COX-2 by forskolin and evaluation of anti-proliferative, pro-apoptotic effects on cervical cancer cells: molecular modelling and in vitro approaches

207 | May 03 2022

Doneti Ravinder et al. found that the FSK engaged the active sites of both the targets by interacting with key residues. [Read the Full Post]

Erythrocyte-cancer Hybrid Membrane-camouflaged Mesoporous Silica Nanoparticles Loaded with Gboxin for Glioma-targeting Therapy

686 | Apr 15 2022

Xiuxiu Jiao et al. found that the (MSNs/Gboxin)@[RBC-U] exhibited significant anti-cancer effected in vitro and the specific self-recognition to GBM cells. [Read the Full Post]

An effective AKT inhibitor-PARP inhibitor combination therapy for recurrent ovarian cancer

467 | Apr 15 2022

Jing Xu et al. suggested that the combination of AKT inhibitor and PARP inhibitor could be a viable approach for clinical testing in recurrent ovarian cancer patients. [Read the Full Post]

Transplantation of autologous bone marrow pre-loaded ex vivo with oncolytic myxoma virus is efficacious against drug-resistant Vk*MYC mouse myeloma

233 | Apr 05 2022

Nancy Y Villa et al. found the utility of autologous BM grafts armed ex vivo with oncolytic MYXV alone or in combination with chemotherapy/immunotherapy to treat drug-resistant MM in vivo. [Read the Full Post]

EgGLUT1 Is Crucial for the Viability of Echinococcus granulosus sensu stricto Metacestode: A New Therapeutic Target?

253 | Apr 04 2022

Kuerbannisha Amahong et al. thought that EgGLUT1-ss was crucial for glucose uptake by the protoscoleces of E. granulosus s.s., and its inhibitor WZB117 had a therapeutic effect on CE. [Read the Full Post]

Influx of kynurenine into the brain is involved in the reduction of ethanol consumption induced by Ro 61-8048 after chronic intermittent ethanol in mice

170 | Mar 10 2022

Leticia Gil de Biedma-Elduayen et al. demonstrated that the modulation of the kynurenine pathway was an effective strategy for the treatment of ethanol dependence in both sexes. [Read the Full Post]

ALDH1A1 maintains the cancer stem-like cells properties of esophageal squamous cell carcinoma by activating the AKT signal pathway and interacting with β-catenin

0 | Mar 07 2022

Wei Wang et al. found that ALDH1A1 interacted with β-catenin, co-localization in KYS-510 cells. [Read the Full Post]

Estimating Drug Efficacy with a Diet-Induced NASH Model in Chimeric Mice with Humanized Livers

395 | Mar 05 2022

Keishi Kisoh et al. showed that CDAHFD feeding induced similar histological changes to human NASH patients, including ballooning, inflammation, apoptosis, regeneration of human hepatocytes, and pericellular and perisinusoidal fibrosis. [Read the Full Post]

The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction

572 | Feb 14 2022

Casandra Gomez-Paredes et al. found that following pharmacological activation in vivo,the heat shock response impairment in tibialis anterior, brain hemispheres and striatum was comparable between zQ175 and R6/2 mice. [Read the Full Post]

Drug-repurposing against COVID-19 by targeting a key signaling pathway: An in silico study

453 | Feb 13 2022

Ki Kwang Oh et al. provided three key elements to alleviate COVID-19 symptoms might be anti-inflammatory effects on SARs-CoV-2-infected lung cells. [Read the Full Post]

Potential effects and application prospect of angiotensin receptor-neprilysin inhibitor in diabetic kidney disease

529 | Feb 05 2022

Xingjian Zhang found that ARNI has application potential in DKD, but there still need clinical studies that focus on DKD patients to determine its effectiveness, safety and underlying mechanism. [Read the Full Post]

A Novel Role for the Regulatory Nod-Like Receptor NLRP12 in Anti-Dengue Virus Response

499 | Jan 28 2022

Xingyu Li et al. demonstrated a novel mechanism that NLRP12 exerted anti-viral properties in DENV and other flaviviruses (JEV, YFV, ZIKV) infection. [Read the Full Post]

The main difference between Alvespimycin vs. 17-DMAG. Biomimetic Platform Based on Mesoporous Platinum for Multisynergistic Cancer Therapy

525 | Jan 27 2022

Gaoqian Zhao et al. showed that 17-DMAG/MPNPs@PM could accumulate in the tumor and effectively inhibit the growth of tumor cells. [Read the Full Post]

Neutrophil Extracellular Traps Are Increased in Chronic Myeloid Leukemia and Are Differentially Affected by Tyrosine Kinase Inhibitors

669 | Jan 24 2022

Alona Telerman et al. thought that CML was associated with increased NET formation, which was augmented by ponatinib, suggesting a possible role for NETs in promoting vascular toxicity in CML. [Read the Full Post]

Discovery of linear unnatural peptides as potent mutant isocitrate dehydrogenase 1 inhibitors by Ugi reaction

175 | Jan 23 2022

Xuechen Zhou et al. found that IDH1could decrease the cellular concentration of 2-HG, and suppress the proliferation of HT1080 and IDH1 mutant-U-87 cells by selectively inhibiting the activity of mutant IDH1. [Read the Full Post]

Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial

223 | Jan 17 2022

Ingo K Mellinghoff et al. found that vorasidenib was well tolerated and showed preliminary antitumor activity in patients with recurrent or progressive nonenhancing mIDH LGG. [Read the Full Post]

Dual-Knockout of Mutant Isocitrate Dehydrogenase 1 and 2 Subtypes Towards Glioma Therapy: Structural Mechanistic Insights on the Role of Vorasidenib

168 | Jan 17 2022

Preantha Poonan et al. provided thorough structural and dynamic insights associated with the dual inhibitory activity of AG-881 towards glioma therapy. [Read the Full Post]

Single cell transcriptomic profiling of neurodegeneration mediated by tau in a novel 3D neuron-astrocyte coculture model

551 | Jan 14 2022

Hannah Rickner et al. demonstrated the power to model the reduction of tau pathology by drug treatment. [Read the Full Post]

Interspecies Differences in Activation of Peroxisome Proliferator-Activated Receptor γ by Pharmaceutical and Environmental Chemicals

195 | Jan 11 2022

Clémentine Garoche et al. demonstrated the importance of the use of species-specific models to study endocrine and metabolism disruption by environmental chemicals. [Read the Full Post]

ECM stiffness-tuned exosomes drive breast cancer motility through thrombospondin-1

241 | Jan 08 2022

Sejal Patwardhan et al. established the pivotal role of exosomal communication in ECM stiffness dependent cell migration with exosomal THBS1 as a master regulator of cancer invasion, which can be further exploited as a potential theranostic for improved breast cancer management. [Read the Full Post]

Small Dense Low-Density Lipoprotein Cholesterol and Cardiovascular Risk in Statin-Treated Patients with Coronary Artery Disease

555 | Dec 28 2021

Junnichi Ishii et al. investigated the relationship between small dense low-density cholesterol (sdLDL-C) and risk of major adverse cardiovascular events (MACE) in patients treated with high- or low-dose statin therapy. [Read the Full Post]

The role of RIPK1 mediated cell death in acute on chronic liver failure

646 | Dec 24 2021

Takayuki Kondo et al. thought that inhibition of RIPK1 was a potential novel therapeutic approach to prevent progression of susceptible patients from no ACLF to ACLF. [Read the Full Post]

Cannabidiol Inhibits In Vitro Human Liver Microsomal Metabolism of Remdesivir: A Promising Adjuvant for COVID-19 Treatment

555 | Dec 19 2021

Aishwarya Saraswat et al. suggested that CBD significantly inhibited human liver microsomal metabolism of RDV and extended its in vitro half-life. [Read the Full Post]

Phase 1 multicenter study of the HSP90 inhibitor SNX-5422 plus carboplatin and paclitaxel in patients with lung cancers

698 | Dec 17 2021

Martin Gutierrez et al. found that the triplet combination of SNX-5422, carboplatin and paclitaxel followed by maintenance SNX-5422 therapy was well-tolerated and showed anti-tumor activity. [Read the Full Post]

Oral Hsp90 inhibitor SNX-5422 attenuates SARS-CoV-2 replication and dampens inflammation in airway cells

608 | Dec 16 2021

Ria Goswami et al. found that SNX-5422 interrupted expression of host factors demonstrated to be crucial for SARS-CoV-2 replication. [Read the Full Post]

d-mannose attenuates lipopolysaccharide-induced osteolysis via CPT1A-Mediated lipid metabolic regulation in macrophages

412 | Dec 13 2021

Zhenzhen Zhang et al. implied that d-mannose attenuated LPS-induced osteolysis by manipulating CPT1A-mediated lipid metabolism in macrophages. [Read the Full Post]

Activation of Yes-Associated Protein/PDZ-Binding Motif Pathway Contributes to Endothelial Dysfunction and Vascular Inflammation in AngiotensinII Hypertension

615 | Dec 08 2021

Qian Xu et al. suggested that AngII induced YAP/TAZ activation via PP2A-dependent dephosphorylation, which might contribute to the impairment of endothelial function and the induction of vascular inflammation in hypertension. [Read the Full Post]

HSP90 inhibition downregulates DNA replication and repair genes via E2F1 repression

804 | Dec 05 2021

Hanqing Liu et al. found that HSP90 inhibitors might be useful in combination therapies for MCL. [Read the Full Post]

Investigation of anticancer activities of STA-9090 (ganetespib) as a second generation HSP90 inhibitor in Saos-2 osteosarcoma cells

791 | Dec 05 2021

Aykut Özgür found the down-regulation of the expression levels of oncogenic genes. [Read the Full Post]

Treatment With Nepicastat Decreases Contextual Traumatic Memories Persistence in Post-traumatic Stress Disorder

251 | Nov 28 2021

Raquel Martinho wt al. found that the increase in Npas4 and Bdnf mRNA expression in the hippocampus might be important to develop a weaker traumatic contextual memory after nepicastat treatment. [Read the Full Post]

The expression of Annexin A1 and A5 mRNA by gonadotropin-releasing hormone in LβT2 gonadotrope cells

502 | Nov 21 2021

Takuya Murata et al. found that ANXA1 mRNA expression was stimulated by GnRH through PKC like ANXA5, and the response of ANXA1 was much larger than that of ANXA5. [Read the Full Post]

Mutual regulation between chicken telomerase reverse transcriptase and the Wnt/β-catenin signalling pathway inhibits apoptosis and promotes the replication of ALV-J in LMH cells

658 | Nov 21 2021

Yong Xiang et al. found that chTERT not only shortened the cell cycle to promote proliferation but also inhibited apoptosis by downregulating the expression of Caspase 3, Caspase 9 and BAX. [Read the Full Post]

Oxidative Phosphorylation Is a Metabolic Vulnerability in Chemotherapy-Resistant Triple-Negative Breast Cancer

435 | Nov 05 2021

Kurt W Evans et al. suggested that triple-negative breast cancer was highly reliant on OXPHOS and that inhibiting OXPHOS might be a novel approach to enhance efficacy of several targeted therapies. [Read the Full Post]

Farnesoid X receptor (FXR) inhibits coagulation process via inducing hepatic antithrombin III expression in mice

375 | Oct 30 2021

Zhi-Lin Luan et al. found that new role of FXR in hemostatic homeostasis and indicates that FXR might act as a potential therapeutic target for diseases related to hypercoagulation. [Read the Full Post]

Daporinad in vitro metabolite profiling via rat, dog, monkey and human liver microsomes by liquid chromatography/quadrupole-orbitrap mass spectrometry

477 | Oct 29 2021

Shan-Dan Qu et al. found that daporinad was metabolized mainly through N-dealkylation, amide hydrolysis, hydrogenation, oxygenation and dehydrogenation. [Read the Full Post]

Hsp90-associated DNA replication checkpoint protein and proteasome-subunit components are involved in the age-related macular degeneration

413 | Oct 29 2021

Chen Xing et al. thought that targeting HSP90AA1, CHEK1, PSMA4, PSMD4, and/or PSMD8 genes through specific miRNAs or small molecules might potentially alleviate the progression of AMD through attenuating RPE senescence. [Read the Full Post]

Co-Expression of CD34, CD90, OV-6 and Cell-Surface Vimentin Defines Cancer Stem Cells of Hepatoblastoma, Which Are Affected by Hsp90 Inhibitor 17-AAG

934 | Oct 26 2021

Mieun Lee-Theilen et al. identified CSCs of hepatoblastoma using CD34, CD90, OV-6 and csVimentin. [Read the Full Post]

Identification of a circRNA-miRNA-mRNA regulatory network for exploring novel therapeutic options for glioma

997 | Oct 25 2021

Yi He et al. highlighted the potential pathogenesis of the circRNA-miRNA-mRNA regulatory network and identified novel therapeutic options for glioma. [Read the Full Post]

HSP90 inhibition acts synergistically with heat to induce a pro-immunogenic form of cell death in colon cancer cells

1269 | Oct 14 2021

Petros X E Mouratidis et al. found that sub-ablative heating could act synergistically with the clinically relevant HSP90 inhibitor NVP-AUY922 to induce a pro-immunogenic form of cell death in colon cancer cells. [Read the Full Post]

Evolution of kinase polypharmacology across HSP90 drug discovery

1259 | Oct 13 2021

Albert A Antolin et al. found that the resorcinol clinical candidates ganetespib and, to a lesser extent, luminespib, displayed unique off-target kinase pharmacology as compared with other HSP90 inhibitors. [Read the Full Post]

Structural basis of the selective activation of enzyme isoforms: Allosteric response to activators of β1- and β2-containing AMPK complexes

897 | Oct 06 2021

Elnaz Aledavood et al. found the design of activators tailored for improving the therapeutic treatment of tissue-specific metabolic disorders. [Read the Full Post]

Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay

407 | Oct 01 2021

Woo Dae Jang et al. found that three drug combinations, omipalisib/remdesivir, tipifarnib/omipalisib, and tipifarnib/remdesivir, showed strong synergistic effects in inhibiting SARS-CoV-2. [Read the Full Post]

Pharmacokinetics of S-epacadostat, an indoleamine 2,3-dioxygenase 1 inhibitor, in dog plasma and identification of its metabolites in vivo and in vitro

616 | Sep 24 2021

Yumu Zhang et al. thought that substituting the nitrogen with sulfur affected the metabolism of the adjacent alkyl side chain. [Read the Full Post]

Overcoming Chemoimmunotherapy-Induced Immunosuppression by Assemblable and Depot Forming Immune Modulating Nanosuspension

515 | Sep 24 2021

Seung Mo Jin et al. found that local administration of AIMS increased T cell infiltration in both local and distant tumors and significantly inhibited the metastasis of tumors to the lung. [Read the Full Post]

Dynamic Remodeling of Membranes and Their Lipids during Acute Hormone-Induced Steroidogenesis in MA-10 Mouse Leydig Tumor Cells

857 | Sep 13 2021

Sathvika Venugopal et al. suggested that PM-ER-mitochondria tethering might be involved in lipid trafficking between organelles. [Read the Full Post]

Small Molecule "Silmitasertib" Repurposed as Inhibitor of Transforming Growth Factor Beta 1 for the Development of Therapeutics for Oral Submucous Fibrosis

1332 | Sep 10 2021

Nezar Boreak et al. suggested that the molecule could be validated and implemented for the treatment of OSMF. [Read the Full Post]

An Iron Shield to Protect Epigallocatehin-3-Gallate from Degradation: Multifunctional Self-Assembled Iron Oxide Nanocarrier Enhances Protein Kinase CK2 Intracellular Targeting and Inhibition

1042 | Sep 10 2021

Luca Fasolato et al. found that the nanohybrid was able to successfully deliver EGCG into cancer cells, displaying impressive protein kinase CK2 inhibition comparable to that obtained with the most specific CK2 inhibitor, CX-4945 (5.5 vs. 3 µM). [Read the Full Post]

Regulation of autoreactive CD4 T cells by FoxO1 signaling in CNS autoimmunity

475 | Sep 08 2021

Emma E Kraus et al. found an important role of FoxO1 signaling in CNS autoimmunity via regulating autoreactive Teff and Treg balance. [Read the Full Post]

Effect of Dickkopf-1 (Dkk-1) and SP600125, a JNK Inhibitor, on Wnt Signaling in Canine Prostate Cancer Growth and Bone Metastases Wachiraphan Supsavhad 1 2, Bardes B Hassan 1 3,

1468 | Sep 05 2021

Wachiraphan Supsavhad et al. showed that SP600125 had the potential to serve as an alternative adjuvant therapy in some early-stage PCa patients, especially those with high Dkk-1 expression. [Read the Full Post]

Pharmacovigilance analysis of cardiac toxicities associated with targeted therapies for metastatic non-small cell lung carcinoma

1026 | Aug 25 2021

Sarah Waliany et al. thought that monitoring for heart failure and arrhythmias should be considered with NSCLC targeted therapies, especially osimertinib. [Read the Full Post]

Local FK506 implants in non-human primates to prevent early acute rejection in vascularized composite allografts

964 | Aug 24 2021

Alexandre G Lellouch et al. showed preliminary results of local FK506 implants in potentially mitigating VCA acute rejection for tolerance protocols based on mixed chimerism approach. [Read the Full Post]

BioID-screening identifies PEAK1 and SHP2 as components of the Alk "proximitome" in neuroblastoma cells

390 | Jul 22 2021

Ezgi Uçkun et al. noted a strong synergistic effect of combined ALK and SHP2 inhibition that was specific to ALK-driven NB cells, suggesting a potential therapeutic option for ALK-driven NB. [Read the Full Post]

Peptide 11R‑VIVIT promotes fracture healing in osteoporotic rats

2928 | Jul 20 2021

Changju Hou et al. demonstrated that 11R‑VIVIT promoted fracture healing in osteoporotic rats and enhanced the osteogenic differentiation of osteoporotic BMSCs by dysregulating the AKT/NFATc1 signaling pathway. [Read the Full Post]

The Tumor Microenvironment in Follicular Lymphoma: Its Pro-Malignancy Role with Therapeutic Potential

659 | Jun 10 2021

Takashi Watanabe found that Tfh, and TFR cells could reinforce the effects of the cytotoxic T cells. [Read the Full Post]

cAMP Signaling-Mediated Phosphorylation of Diacylglycerol Lipase α Regulates Interaction With Ankyrin-G and Dendritic Spine Morphology

366 | Jun 09 2021

Sehyoun Yoon et al. found that ANK3 and DAGLA, both neuropsychiatric disorder genes, interacted in a complex to regulate spine morphology. [Read the Full Post]

Nonsense-mediated mRNA decay efficiency influences bleeding severity in ITGA2B c.2659C > T (p.Q887X) knock-in mice

804 | May 10 2021

Zhanli Xie et al. found that NMD efficiency potentially influenced bleeding severity in ITGA2B c.2659C > T (p.Q887X) KI mice. [Read the Full Post]

High BRCA2 Gene Expression is Associated with Aggressive and Highly Proliferative Breast Cancer

720 | May 10 2021

Vikas Satyananda et al. thought that BRCA2 gene expression might become a candidate marker for aggressive biology and to tailor specific treatment strategies in the future. [Read the Full Post]

Loss of FADD and Caspases Affects the Response of T-Cell Leukemia Jurkat Cells to Anti-Cancer Drugs

534 | Apr 26 2021

Zuzana Mrkvová et al. thought that a combination of TNF-α and smac mimetic could be a suitable strategy for overcoming resistance to therapy in cells unable to trigger apoptosis. [Read the Full Post]

Involvement of GLUT1 and GLUT3 in the growth of canine melanoma cells

522 | Apr 25 2021

Yoko Suwabe et al. suggested that glucose uptake via GLUT1 and GLUT3 played a crucial role for the growth of canine melanoma cells. [Read the Full Post]

A proprotein convertase subtilisin/kexin type 9 inhibitor provides comparable efficacy with lower detriment than statins on mitochondria of oxidative muscle of obese estrogen-deprived rats

525 | Apr 06 2021

Chanisa Thonusin et al. showed that 17β-Estradiol exhibited the greatest efficacy on the attenuation of obesity with the least harmful effect on skeletal muscle in a model of menopause with obesity, yet its effect on the treatment of hyperlipidemia was inferior to those of standard lipid-lowering agents. [Read the Full Post]

Addiction and the kynurenine pathway: A new dancing couple?

377 | Mar 23 2021

Nuria Morales-Puerto et al. discussed ethanol, nicotine, cannabis, amphetamines, cocaine and opioids and new prospects in the drug research field were proposed [Read the Full Post]

ALDH1A1 maintains the cancer stem-like cells properties of esophageal squamous cell carcinoma by activating the AKT signal pathway and interacting with β-catenin

274 | Mar 18 2021

Wei Wang et al. found that ALDH1A1 expression maintained the CSC properties of ESCC cells. [Read the Full Post]

Beneficial effects of elafibranor on NASH in E3L.CETP mice and differences between mice and men

595 | Mar 17 2021

Anita M van den Hoek et al. concluded that elafibranor might be particularly useful to reduce hepatic inflammation and could be a pharmacologically useful agent for human NASH, but probably in combination with other agents. [Read the Full Post]

Discovery of repurposing drug candidates for the treatment of diseases caused by pathogenic free-living amoebae

994 | Feb 25 2021

Christopher A Rice et al. demonstrated the utility of phenotypic screens for discovery of new drugs for pathogenic free-living amoebae, including Acanthamoeba for the first time. [Read the Full Post]

Priming with HDAC Inhibitors Sensitizes Ovarian Cancer Cells to Treatment with Cisplatin and HSP90 Inhibitors

878 | Feb 24 2021

Ana J Rodrigues Moita et al. found that priming with HDACi sensitized ovarian cancer cells to treatment with HSP90i or cisplatin and had an influence on the development of cisplatin resistance, both of which might contribute to an improved ovarian cancer treatment. [Read the Full Post]

Hospitalization and Mortality in Patients With Heart Failure Treated With Sacubitril/Valsartan vs. Enalapril: A Real-World, Population-Based Study

762 | Feb 12 2021

Swathi Pathadka et al. found that in real-world settings, sacubitril/valsartan was associated with improved survival and reduced heart failure-related hospitalization compared to enalapril in Asian patients with heart failure. [Read the Full Post]

Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer

696 | Feb 03 2021

Chih-Yang Wang et al. found that upregulation of PPARA and lipid metabolism-related genes were potential pathways in the carcinogenesis and development of ampullary cancer. [Read the Full Post]

17-DMAG dually inhibits Hsp90 and histone lysine demethylases in alveolar rhabdomyosarcoma

849 | Feb 03 2021

Shivendra Singh et al. indicated that targeting KDM in combination with chemotherapy might serve as a therapeutic approach to PAX3-FOXO1-positive aRMS. [Read the Full Post]

Population pharmacokinetic and exposure-response analyses of ivosidenib in patients with IDH1-mutant advanced hematologic malignancies

320 | Jan 30 2021

Xuemin Jiang et al. provided a framework to describe the relationship among ivosidenib dose, exposure, and clinical end points. [Read the Full Post]

Neutrophil Extracellular Traps in Atherosclerosis and Thrombosis

882 | Jan 30 2021

Thomas M Hofbaue et al. found mechanisms of NET formation, evidence for their involvement in atherosclerosis and thrombosis, and potential therapeutic regimens specifically targeting NET components. [Read the Full Post]

Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual Inhibitor of Mutant IDH1 and 2 for Treatment of Glioma

402 | Jan 25 2021

Zenon Konteatis et al. described the discovery of vorasidenib (AG-881), a potent, oral, brain-penetrant dual inhibitor of both mIDH1 and mIDH2. [Read the Full Post]

MR-detectable metabolic biomarkers of response to mutant IDH inhibition in low-grade glioma

384 | Jan 25 2021

Abigail R Molloy et al. identified potential 1H- and 13C-MRS-detectable biomarkers of response to IDH1mut inhibition in gliomas. [Read the Full Post]

Regulation of cytochrome P450 4F11 expression by liver X receptor alpha

369 | Jan 21 2021

Tao Zhang et al. found that the regulation of CYP4F11 might contribute to the anti-inflammatory activity of LXRα agonists. [Read the Full Post]

Hypoxia-reoxygenation induces macrophage polarization and causes the release of exosomal miR-29a to mediate cardiomyocyte pyroptosis

342 | Jan 18 2021

Yan Wang et al. found that HR treatment induced macrophage polarization towards the M1 phenotype, which mediated CM pyroptosis through exosomal miR-29a transfer by targeting MCL-1. [Read the Full Post]

Repurposing FDA Approved Drugs as JNK3 Inhibitor for Prevention of Neuroinflammation Induced by MCAO in Rats

708 | Jan 06 2021

Zikra Zulfiqar et al. demonstrated that the novel FDA-approved medications attenuate ischemic stroke-induced neuronal degeneration, possibly by inhibiting JNK3. [Read the Full Post]

Synergistic Utilization of Necrostatin-1 and Z-VAD-FMK Efficiently Promotes the Survival of Compression-Induced Nucleus Pulposus Cells via Alleviating Mitochondrial Dysfunction

810 | Jan 03 2021

Songfeng Chen et al. found that the synergistic utilization of Necrostatin-1 and Z-VAD-FMK was a very worthwhile solution in preventing compression-mediated NP cells death, which might be largely attributed to restored mitochondrial function. [Read the Full Post]

Potent and Specific Inhibition of NTCP-Mediated HBV/HDV Infection and Substrate Transporting by a Novel, Oral-Available Cyclosporine A Analogue

573 | Dec 29 2020

Yang Liu et al. found that 27A served as a promising lead for the development of novel anti-HDV/HBV agents. [Read the Full Post]

Deciphering the Inhibition Mechanism of under Trial Hsp90 Inhibitors and Their Analogues: A Comparative Molecular Dynamics Simulation

720 | Dec 28 2020

Asma Nazar et al. suggested that under trial Hsp90 inhibitors MPC-3100 could be a potential starting point into the development of potential anticancer agents with the possibility of future directions for the improvement of early existing Hsp90 inhibitors CNF-2024 and SNX-5422 as an anticancer agent. [Read the Full Post]

Heat Shock Protein 90 Inhibitors AUY922, BIIB021 and SNX5422 Induce Bim-mediated Death of Thyroid Carcinoma Cells

670 | Dec 27 2020

Si Hyoung Kim et al. found that AUY922, BIIB021 and SNX5422 induced cytotoxicity by modulating Bim and ERK1/2, AKT and AMPK signaling in thyroid carcinoma cells. [Read the Full Post]

ScatLay: utilizing transcriptome-wide noise for identifying and visualizing differentially expressed genes

531 | Dec 24 2020

Thuy Tien Bui et al. provided a wider coverage of DE genes, and would likely pave way for finding more novel regulatory genes in future works. [Read the Full Post]

FTY720 induces ferroptosis and autophagy via PP2A/AMPK pathway in multiple myeloma cells

722 | Dec 20 2020

Yuan Zhong et al. provided a new perspective on the treatment of MM. [Read the Full Post]

HSP90 Inhibitor Ganetespib (STA-9090) Inhibits Tumor Growth in c-Myc-Dependent Esophageal Squamous Cell Carcinoma

845 | Dec 17 2020

Liuliu Guan et al. supported that the HSP90 inhibitor, STA-9090, suppressed the expression of the MYC protein and interferes with HSP90-MYC protein-protein interaction. [Read the Full Post]

Ganetespib in Combination with Pemetrexed-Platinum Chemotherapy in Patients with Pleural Mesothelioma (MESO-02): A Phase Ib Trial

872 | Dec 16 2020

Dean A Fennell et al. found that ganetespib could be combined safely with pemetrexed and platinum chemotherapy to treat patients with MPM. [Read the Full Post]

Lack of zinc finger protein 521 upregulates dopamine β-hydroxylase expression in the mouse brain, leading to abnormal behavior

354 | Dec 10 2020

Nobutaka Ohkubo et al. suggested that the lack of ZFP521 upregulated the expression of DBH, which led to a decrease in the DA level and an increase in the NA level in the brain, resulting in abnormal behaviors. [Read the Full Post]

LGR5 induces β activation and augments tumor progression by activating STAT3 in human intrahepatic cholangiocarcinoma

1307 | Dec 04 2020

Keishi Kawasaki et al. thought that LGR5 was an excellent prognostic predictor and a promising therapeutic target for ICC. [Read the Full Post]

Component of nicotine-induced intracellular calcium elevation mediated through α3- and α5-containing nicotinic acetylcholine receptors are regulated by cyclic AMP in SH-SY 5Y cells

640 | Dec 03 2020

Tamayo Takahashi et al. suggested that α3 * and α5 * nAChR-mediated Ca2+ influx was possibly regulated by cAMP at the transcriptional level. [Read the Full Post]

RIP3 dependent NLRP3 inflammasome activation is implicated in acute lung injury in mice

790 | Nov 18 2020

Jingxian Chen et al. showed that RIP3 participated in the NLRP3 inflammasome activation in infiltrating macrophages in ALI induced by LPS. [Read the Full Post]

Notoginseng Leaf Triterpenes Ameliorates OGD/R-Induced Neuronal Injury via SIRT1/2/3-Foxo3a-MnSOD/PGC-1 α Signaling Pathways Mediated by the NAMPT-NAD Pathway

419 | Nov 07 2020

Weijie Xie et al. found that PNGL, as a new drug candidate, had a pivotal role in mitochondrial homeostasis and energy metabolism therapy via NAMPT against OGD-induced SH-SY5Y cell injury. [Read the Full Post]

Dehydrodiconiferyl alcohol, a lignan from Herpetospermum pedunculosum, alleviates cholestasis by activating pathways associated with the farnesoid X receptor

414 | Nov 07 2020

Xiaodong Wei et al. thought that DA might represent an effective agonist for FXR had significant therapeutic potential for the treatment of cholestatic liver injury. [Read the Full Post]

Pre-B cell colony enhancing factor induces Nampt-dependent translocation of the insulin receptor out of lipid microdomains in A549 lung epithelial cells

0 | Nov 06 2020

Qianyi Peng et al. concluded that PBEF could inhibit insulin signaling through the IR by Nampt-dependent promotion of IR translocation into the nonraft domains of A549 epithelial cells. [Read the Full Post]

VDAC upregulation and αTAT1‑mediated α‑tubulin acetylation contribute to tanespimycin‑induced apoptosis in Calu‑1 cells

2154 | Nov 02 2020

Qilin Wang et al. provided evidence for the use of a combination of drugs that target VDAC1 and tubulin to induce tumour cell apoptosis. [Read the Full Post]

Identification of Subtype-Specific Metastasis-Related Genetic Signatures in Sarcoma

946 | Nov 02 2020

Ya-Ling Li et al. provided new insights into the pathogenesis, diagnosis, treatment, and prognosis of sarcomas and provided new directions for further study of sarcoma. [Read the Full Post]

Hsp90 Inhibitor; NVP-AUY922 in Combination with Doxorubicin Induces Apoptosis and Downregulates VEGF in MCF-7 Breast Cancer Cell Line

963 | Oct 16 2020

Mahshid Mohammadian et al. indicated an effective action of NVP-AUY922 in combined with DOX in this cell line. [Read the Full Post]

Heat Shock Protein 90 (Hsp90)-Inhibitor-Luminespib-Loaded-Protein-Based Nanoformulation for Cancer Therapy

997 | Oct 15 2020

Ankit K Rochani et al.suggested that DNP-based aqueous nanoformulations could be used in both pancreatic (MIA PaCa-2) and breast (MCF-7) cancer therapy. [Read the Full Post]

Myeloid deletion and therapeutic activation of AMPK do not alter atherosclerosis in male or female mice

681 | Oct 02 2020

Nicholas D LeBlond et al. suggested that intervention with the first-generation AMPK activator A-769662 was not able to stem the progression of atherosclerosis. [Read the Full Post]

Tipifarnib as a Precision Therapy for HRAS-Mutant Head and Neck Squamous Cell Carcinomas

342 | Sep 24 2020

Mara Gilardi et al. supported that HRAS represented a druggable oncogene in HNSCC through FTase inhibition by tipifarnib, thereby identifying a precision therapeutic option for HNSCCs harboring HRAS mutations. [Read the Full Post]

Clinical Significance of Program Death Ligand-1 and Indoleamine-2,3-Dioxygenase Expression in Colorectal Carcinoma

485 | Sep 17 2020

Sean Hacking et al. supported the theoretical foundation for targeting PD-L1 and IDO-1 in CRC, which now needed verification in well-designed robust clinical trials. [Read the Full Post]

Peptide vaccination directed against IDO1-expressing immune cells elicits CD8 + and CD4 + T-cell-mediated antitumor immunity and enhanced anti-PD1 responses

470 | Sep 17 2020

Souvik Dey et al. found that the in vivo antitumor effects demonstrated with IDO1-based vaccines via targeting of the tumor microenvironment highlighted the utility of mouse models for further exploration and refinement of this novel vaccine-based approach to IDO1-directed cancer therapy and its potential to improve patient response rates to anti-PD1 therapy. [Read the Full Post]

Bucladesine Attenuates Spatial Learning and Hippocampal Mitochondrial Impairments Induced by 3, 4-Methylenedioxymethamphetamine (MDMA)

614 | Aug 31 2020

Ghorban Taghizadeh et al. highlighted the role of cAMP/PKA signaling in MDMA-induced memory and mitochondrial defects. [Read the Full Post]

Protein Kinase CK2 in Cancer Energetics

1110 | Aug 27 2020

Eduardo Silva-Pavez et al. proposed that the specific inhibition of CK2 might lead to a catastrophic death of cancer cells, which could become a feasible therapeutic strategy to beat this devastating disease. [Read the Full Post]

Casein kinase 2 inhibitor CX-4945 elicits an anti-Warburg effects through the downregulation of TAp73 and inhibits gastric tumorigenesis

992 | Aug 27 2020

Shengli Tang et al. suggested that CX-4945 elicited an anti-Warburg effects in gastric cancer overexpressing Tap73 and inhibited gastric tumorigenesis. [Read the Full Post]

MicroRNA-182 exacerbates blood-brain barrier (BBB) disruption by downregulating the mTOR/FOXO1 pathway in cerebral ischemia

540 | Aug 24 2020

Tongshuai Zhang et al. found that miR-182 might be a potential target for the treatment of BBB disruption during cerebral ischemia. [Read the Full Post]

Alcohol-induced CYP2E1, Mitochondrial Dynamics and Retrograde Signaling in Human Hepatic 3D Organoids

1103 | Aug 03 2020

Rajesh Angireddy et al. presented a mechanistic link between CYP2E1 function and alcohol mediated mitochondrial dysfunction, retrograde signaling, and activation of hepatic steatosis in a 3D organoid system that closely recapitulated the in vivo liver response. [Read the Full Post]

Disrupting Phosphatase SHP2 in Macrophages Protects Mice From High-Fat Diet-Induced Hepatic Steatosis and Insulin Resistance by Elevating IL-18 Levels

497 | Jun 23 2020

Wen Liu et al. concluded that pharmacological inhibition of SHP2 might represent a possible therapeutic strategy for the management of type 2 diabetes. [Read the Full Post]

Effects of the PI3K/Akt Signaling Pathway on the Apoptosis of Early Host Cells Infected With Eimeria Tenella

1517 | Jun 21 2020

Xuesong Zhang et al. investigated the role of PI3K/Akt signaling pathway on host cell apoptosis in the early infection of Eimeria tenella,the early development of E. tenella could inhibit host cell apoptosis by downregulating the Caspase-3 activity. [Read the Full Post]

Evaluation of Musculoskeletal Phenotype of the G608G Progeria Mouse Model With Lonafarnib, Pravastatin, and Zoledronic Acid as Treatment Groups

353 | Jun 10 2020

Maria B Cubria et al. characterized the musculoskeletal phenotype of the homozygous G608G BAC-transgenic progeria mouse model, and determined the phenotype changes of HGPS mice after a five-arm preclinical trial of different treatment combinations with lonafarnib, pravastatin, and zoledronic acid. [Read the Full Post]

TGF-β1-mediated Repression of SLC7A11 Drives Vulnerability to GPX4 Inhibition in Hepatocellular Carcinoma Cells

572 | Jun 09 2020

Do Hyung Kim et al. showed that TGF-β1 repressed xCT expression via Smad3 activation and enhanced lipid peroxidation in hepatocellular carcinoma cells with an early TGF-β1 signature, which would benefit from the targeting of GPX4. [Read the Full Post]

Effects of nanoparticle-mediated delivery of pitavastatin on atherosclerotic plaques in ApoE-knockout mice and THP-1-derived macrophages

402 | May 05 2020

Sun Y et al. demonstrated that pitavastatin-NP administration was more effective in attenuating the development of atherosclerotic plaques compared with systemic administration of pitavastatin. [Read the Full Post]

A Phase I Study of PF-04929113 (SNX-5422), an Orally Bioavailable Heat Shock Protein 90 Inhibitor, in Patients With Refractory Solid Tumor Malignancies and Lymphomas

695 | Apr 19 2020

Arun Rajan et al. showed that PF-04929113 administered orally twice a week is well tolerated and inhibits its intended target Hsp90. No objective responses were seen, but long-lasting stabilizations were obtained. Although no clinically significant drug-related ocular toxicity was seen in this study, the development of PF-04929113 has been discontinued because of ocular toxicity seen in animal models and in a separate phase I study. [Read the Full Post]

SNX-2112, a Selective Hsp90 Inhibitor, Potently Inhibits Tumor Cell Growth, Angiogenesis, and Osteoclastogenesis in Multiple Myeloma and Other Hematologic Tumors by Abrogating Signaling via Akt and ERK

663 | Apr 19 2020

Yutaka Okawa et al. provided the framework for clinical studies of SNX-2112 to improve patient outcome in MM and other hematologic malignancies. [Read the Full Post]

Identifying off-target effects of etomoxir reveals that carnitine palmitoyltransferase I is essential for cancer cell proliferation independent of β-oxidation

853 | Apr 12 2020

Yao CH et al. suggested that transport of at least some long-chain fatty acids into the mitochondria by CPT1 may be required for anabolic processes that support healthy mitochondrial function and cancer cell proliferation independent of FAO. [Read the Full Post]

LB-100, a novel Protein Phosphatase 2A (PP2A) inhibitor, sensitizes malignant meningioma cells to the therapeutic effects of radiation

447 | Mar 19 2020

Ho WS et al. provided convincing preclinical data to support the use of LB-100 as a radiosensitizing agent for treatment of malignant meningioma. Its potential for clinical application deserves further investigation. [Read the Full Post]

Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD)

827 | Mar 15 2020

Nikonova AS et al. identified a new biologic activity for HSP90 and support a cilia-based mechanism for cyst repression.-Nikonova, A. S., Deneka, A. Y., Kiseleva, A. A., Korobeynikov, V., Gaponova, A., Serebriiskii, I. G., Kopp, M. C., Hensley, H. H., Seeger-Nukpezah, T. N., Somlo, S., Proia, D. A., Golemis, E. A. Ganetespib limits ciliation and cystogenesis in autosomal-dominant polycystic kidney disease (ADPKD). [Read the Full Post]

The novel HSP90 inhibitor STA-9090 exhibits activity against Kit-dependent and -independent malignant mast cell tumors

769 | Mar 15 2020

Lin TY et al. showed that STA-9090 exhibits broad activity against mast cells expressing WT or mutant Kit, suggesting it may be an effective agent in the clinical setting against mast cell malignancies. [Read the Full Post]

mbined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet

646 | Mar 13 2020

Luo F et al. suggested that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages. [Read the Full Post]

The Role and Mechanism of CRT0066101 as an Effective Drug for Treatment of Triple-Negative Breast Cancer

919 | Mar 09 2020

Liu Y et al. indicated that PRKD inhibitor CRT0066101 exhibits anti-TNBC effects via modulating a phosphor-signaling network and inhibiting the phosphorylation of many cancer-driving factors, including MYC, MAPK1/3, AKT, YAP, and CDC2, providing insight into the important roles as well as the molecular mechanism of CRT0066101 as an effective drug for TNBC. [Read the Full Post]

Evaluation of the dopamine β-hydroxylase (DβH) inhibitor nepicastat in participants who meet criteria for cocaine use disorder

866 | Mar 04 2020

De La Garza R 2nd et al. indicated that nepicastat is safe when co-administered with cocaine and may suppress its positive subjective effects, and may be viable as a pharmacotherapy for treatment of cocaine use disorder. [Read the Full Post]

RIP3 inhibition protects locomotion function through ameliorating mitochondrial antioxidative capacity after spinal cord injury

0 | Feb 13 2020

Wang Y et al. suggested improving antioxidative capacity as a potential multifunctional treatment after SCI and the broader possibility of targeting RIP3 activity as a therapeutic window for spinal neuroprotective intervention. [Read the Full Post]

MYC promotes tryptophan uptake and metabolism by the kynurenine pathway in colon cancer

747 | Jan 17 2020

Venkateswaran N et al. proposed that limiting cellular kynurenine or its downstream targets could present a new strategy to reduce the proliferation of MYC-dependent cancer cells. [Read the Full Post]

Farnesoid X receptor agonist GW4064 ameliorates lipopolysaccharide-induced ileocolitis through TLR4/MyD88 pathway related mitochondrial dysfunction in mice

425 | Jan 15 2020

Liu HM et al. demonstrated that central roles of FXR in coordinating regulation of both inflammation and mitochondrial dysfunction. We propose that GW4064 is promising therapeutic agent for treatment of ileocolitis. [Read the Full Post]

Selective Cytotoxicity of the NAMPT Inhibitor FK866 Toward Gastric Cancer Cells With Markers of the Epithelial-Mesenchymal Transition, Due to Loss of NAPRT

638 | Jan 14 2020

Lee J et al. showed that FK866 selectively kills gastric cancer cells with an EMT gene expression signature by inhibiting nicotinamide phosphoribosyltransferase in cells with NAPRT deficiency. Loss of NAPRT expression, frequently through promoter hypermethylation, is observed in many gastric tumors of the EMT subtype. FK866 might be used to treat patients with tumors of this subtype. [Read the Full Post]

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

771 | Jan 14 2020

Shi C et al. indicated that APO866 protects NP cells and induces autophagy by inhibiting IL-1β-induced NP cell degeneration and apoptosis, which may have therapeutic potential in IDD. [Read the Full Post]

Pre-B cell colony enhancing factor induces Nampt-dependent translocation of the insulin receptor out of lipid microdomains in A549 lung epithelial cells

0 | Jan 13 2020

Peng Q et al. concluded that PBEF can inhibit insulin signaling through the IR by Nampt-dependent promotion of IR translocation into the nonraft domains of A549 epithelial cells. PBEF-induced alterations in the spatial geometry of the IR provide a mechanistic explanation for insulin resistance in inflammatory states associated with upregulation of PBEF. [Read the Full Post]

17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model

912 | Jan 08 2020

Joshi SS et al. indicated their sdudies support a role for 17-AAG and HSP90 inhibition in enhancing cellular immunotherapy for melanoma. [Read the Full Post]

Tanespimycin as antitumor therapy

0 | Jan 07 2020

Dimopoulos MA et al. indiacated that tanespimycin represents a promising new agent for the treatment of relapsed/refractory MM. Results of ongoing and future trials will determine the role of tanespimycin both in MM and other malignancies, including breast cancer. [Read the Full Post]

Hsp90 inhibitors induce the unfolded protein response in bovine and mice lung cells

838 | Dec 19 2019

Kubra KT et al. demonstrated that Hsp90 inhibition triggers the activities of the unfolded protein response, and suggests that this molecular machinery contributes in the protective action of Hsp90 inhibitors in the lung microvasculature. [Read the Full Post]

NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo

0 | Dec 19 2019

Lian J et al. indicated that NVP-AUY922 exhibits potent anti-PCC activities in vitro and in vivo and represents a promising therapeutic small molecule for treating malignant PCC. [Read the Full Post]

Activity of the Hsp90 inhibitor luminespib among non-small-cell lung cancers harboring EGFR exon 20 insertions

819 | Dec 18 2019

Piotrowska Z et al.showed that this study met its primary end point, suggesting that luminespib may be an active therapy for advanced NSCLC patients with EGFR ins20. Luminespib is generally well-tolerated, though reversible low-grade ocular toxicity is common. Further study of luminespib and other hsp90 inhibitors in this population is warranted. [Read the Full Post]

Effect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue

712 | Dec 09 2019

Rameshrad M et al. demonstrated that activation of AMPK, by A-769662 agent, could inhibit Tlr-4 expression and activity, suggesting a link between AMPK and Tlr-4 in heart tissue. [Read the Full Post]

Tipifarnib prevents development of hypoxia-induced pulmonary hypertension

0 | Dec 02 2019

Duluc L et al. demonstrated the importance of protein farnesylation in pulmonary vascular remodelling and provides a rationale for selective targeting of this pathway in pulmonary hypertension. [Read the Full Post]

First-in-Human Phase I Study of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase-1 Epacadostat (INCB024360) in Patients with Advanced Solid Malignancies

707 | Nov 25 2019

Beatty GL et al. showed that epacadostat was generally well tolerated, effectively normalized kynurenine levels, and produced maximal inhibition of IDO1 activity at doses of ≥100 mg BID. Studies investigating epacadostat in combination with other immunomodulatory drugs are ongoing. [Read the Full Post]

Updates in the Clinical Development of Epacadostat and Other Indoleamine 2,3-Dioxygenase 1 Inhibitors (IDO1) for Human Cancers

720 | Nov 24 2019

Komiya T et al. indicated that IDO1 is a promising target that can improve the treatment outcome in the field of Immuno-oncology. Several orally available IDO1 inhibitors including Epacadostat have entered human clinical trials over the last few years without a major safety concern. Although there is no objective response in single-agent trials, combination regimens with PD-1 inhibitors appear to exceed the activity of PD-1 inhibitors alone. Recent phase III ECHO 301 trial testing the combination of Epacadostat with Pembrolizumab in melanoma did not show superior outcome compared to Pembrolizumab alone. This lead to halting of other phase III trials using IDO1 inhibitors. In this minireview, we will discuss the recent clinical development of Epacadostat and other IDO1 inhibitors. [Read the Full Post]

CX-4945: the protein kinase CK2 inhibitor and anti-cancer drug shows anti-fungal activity

1096 | Nov 07 2019

Masłyk M et al. indicated their data unveil the dual-activity of CX-4945; when used in anti-cancer therapy, it may simultaneously prevent cancer-associated candidiasis. [Read the Full Post]

FoxO1 regulates myocardial glucose oxidation rates via transcriptional control of pyruvate dehydrogenase kinase 4 expression

578 | Nov 02 2019

Gopal K et al. demonstrated that pyruvate dehydrogenase kinase 4 is a direct transcriptional target of FoxO1 (but not FoxO3/FoxO4) in the heart. Furthermore, we report here, for the first time, that FoxO1 inhibition increases glucose oxidation in the isolated working mouse heart. [Read the Full Post]

Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV-1 study

481 | Sep 05 2019

Yurdaydin C et al. showed the cytochrome P450 3A4 inhibitor, RTV, allows a lower LNF dose to be used while achieving higher levels of postabsorption LNF, yielding better antiviral responses and tolerability. In addition, combining LNF with PEG-IFNα achieved more substantial and rapid HDV-RNA reduction, compared to historical responses with PEG-IFNα alone. Twelve weeks of LNF can result in posttreatment HDV-RNA negativity in some patients, which we speculate results from restoring favorable immune responses. These results support further development of LNF with RTV boosting and exploration of the combination of LNF with PEG-IFN. [Read the Full Post]

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

0 | Aug 19 2019

Chen YN et al. demonstrated that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers. [Read the Full Post]

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

699 | Aug 09 2019

Chen YN et al. demonstrated that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers. [Read the Full Post]

Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol Homeostasis

540 | Jun 17 2019

Li H et al. showed taht activation of FXR induces FNDC5 mRNA expression in human and increased the circulating level of Irisin in Rhesus macaques. FNDC5/Irisin is a direct transcriptional target of FXR. Irisin may be a novel therapeutic strategy for dyslipidemia and atherosclerosis. [Read the Full Post]

RIP3 inhibition protects locomotion function through ameliorating mitochondrial antioxidative capacity after spinal cord injury

895 | Jun 17 2019

Wang Y et al. suggested improving antioxidative capacity as a potential multifunctional treatment after SCI and the broader possibility of targeting RIP3 activity as a therapeutic window for spinal neuroprotective intervention. [Read the Full Post]

Lonafarnib synergizes with azoles against Aspergillus spp. and Exophiala spp

480 | Jun 13 2019

Qiao J et al. demonstrated that lonafarnib could enhance the in vitro antifungal activity of itraconazole, posaconazole and voriconazole against Aspergillus spp. and E. dermatitidis, suggesting that azoles, especially itraconazole and posaconazole, combined with farnesyltransferase inhibitor might provide a potential strategy to the management of Aspergillus and Exophiala infections. However, further studies are warranted to elucidate the underlying mechanism and to investigate the potential of reliable and safe application in clinical practice. [Read the Full Post]

CX-4945, a Selective Inhibitor of Casein Kinase 2, Synergizes with B Cell Receptor Signaling Inhibitors in Inducing Diffuse Large B Cell Lymphoma Cell Death

1061 | Jun 08 2019

Mandato E et al. suggested a role for CK2 downstream of the BCR in controlling survival pathways crucial for cell growth of different DLBCL subtypes. Also, the use of CX-4945 in combination with BCR signaling blockers could represent a novel rational therapeutic approach in the DLBCL. [Read the Full Post]

Targeting FoxO1 with AS1842856 suppresses adipogenesis

592 | Jun 02 2019

Zou P et al. suggested AS1842856 can be an anti-obesity agent that warrants further investigation. [Read the Full Post]

NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo

1110 | May 31 2019

Lian J et al. showed that NVP-AUY922 exhibits potent anti-PCC activities in vitro and in vivo and represents a promising therapeutic small molecule for treating malignant PCC. [Read the Full Post]

Quantitative phosphoproteomic analysis of acquired cancer drug resistance to pazopanib and dasatinib

1022 | May 26 2019

Vyse S et al. provided a useful resource detailing the candidate signalling determinants of acquired TKI resistance; and reveals a therapeutic approach of inhibiting HSP90 function as a means of salvage therapy to overcome pazopanib and dasatinib resistance. [Read the Full Post]

AMP-activated protein kinase (AMPK) activator A-769662 increases intracellular calcium and ATP release from astrocytes in an AMPK-independent manner

972 | May 23 2019

Vlachaki Walker JM et al. indicated that AMPK is required to maintain basal eATP levels but is not required for A-769662-induced increases in eATP. A-769662 (>50 μM) enhanced intracellular calcium levels leading to ATP release in an AMPK and purinergic receptor independent pathway. [Read the Full Post]

Tipifarnib prevents development of hypoxia-induced pulmonary hypertension

566 | May 22 2019

Duluc L et al. demonstrated the importance of protein farnesylation in pulmonary vascular remodelling and provides a rationale for selective targeting of this pathway in pulmonary hypertension. [Read the Full Post]

Effects of EF-24, RAD001, and paclitaxel on the expression profiles of apoptotic and anti-apoptotic genes

1098 | May 15 2019

Alp E et al. showed that response of these cells to paclitaxel, EF-24, and RAD001 was found different at the transcriptional level of apoptotic and antiapoptotic genes. [Read the Full Post]

Effects of Epacadostat on Brain Extracellular Fluid Concentrations of Serotonin -- An Intracerebral Microdialysis Study in Sprague-Dawley Rats

772 | May 14 2019

Zhang Y et al. suggested that serotonin syndrome is unlikely following treatment with either epacadostat alone or with combination with MAOIs such as linezolid. [Read the Full Post]

Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling

1105 | May 06 2019

Kuusanmäki H et al. showed alternative approaches to inhibit STAT3 activity and suggest Hsp90 as a therapeutic target in lymphoproliferative disorders with constitutively active STAT3. [Read the Full Post]

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models

0 | May 04 2019

Lehmann C et al. provided functional and molecular insight on the superior anti-tumor activity of combined idasanutlin and venetoclax treatment in AML and support its further exploration in clinical studies. [Read the Full Post]

Nicotinamide phosphoribosyltransferase inhibitor APO866 induces C6 glioblastoma cell death via autophagy

545 | Apr 23 2019

Yang P et al indicated that APO866 induced pro-death autophagy in C6 glioblastoma cells by decreasing intracellular NAD, and low concentration of APO866 can be used as an autophagy inducer in autophagic-death sensitive glioblastoma. [Read the Full Post]

FK866-induced NAMPT inhibition activates AMPK and downregulates mTOR signaling in hepatocarcinoma cells

596 | Apr 22 2019

Schuster S et al. revealed an important role of the NAMPT-mediated NAD salvage pathway in the energy homeostasis of hepatocarcinoma cells and suggest NAMPT inhibition as a potential treatment option for HCC. [Read the Full Post]

Pre-B cell colony enhancing factor induces Nampt-dependent translocation of the insulin receptor out of lipid microdomains in A549 lung epithelial cells

770 | Apr 15 2019

Peng Q et al. concluded that PBEF can inhibit insulin signaling through the IR by Nampt-dependent promotion of IR translocation into the nonraft domains of A549 epithelial cells. PBEF-induced alterations in the spatial geometry of the IR provide a mechanistic explanation for insulin resistance in inflammatory states associated with upregulation of PBEF. [Read the Full Post]

CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells

1086 | Apr 13 2019

Silva-Pavez E et al. suggested that an aberrantly elevated expression/activity of CK2 may play a key role in CRC, promoting cell viability and proliferation in untreated cells, however, its inhibition with silmitasertib promotes methuosis-like cell death associated to massive catastrophic vacuolization, accounting for decreased tumorigenicity at later times. These characteristics of silmitasertib support a potential therapeutic use in CRC patients and probably other CK2-dependent cancers. [Read the Full Post]

Clinical evaluation of laboratory methods to monitor exposure of rivaroxaban at trough and peak in patients with atrial fibrillation

554 | Mar 15 2019

Al-Aieshy F et al. found that the POC assay for PT-INR could be useful to indicate high exposure to rivaroxaban in emergency situations although further validation is required. [Read the Full Post]

Tanespimycin as antitumor therapy

1266 | Feb 24 2019

Dimopoulos MA et al. showed that tanespimycin represents a promising new agent for the treatment of relapsed/refractory MM. Results of ongoing and future trials will determine the role of tanespimycin both in MM and other malignancies, including breast cancer. [Read the Full Post]

Effects of cancer-associated point mutations on the structure, function, and stability of succinate dehydrogenase A

1210 | Feb 22 2019

Cao ZF et al. provided information important for understanding the molecular mechanisms of SDHA mutations in tumors. [Read the Full Post]

The Phosphodiesterase 10A Inhibitor PF-2545920 Enhances Hippocampal Excitability and Seizure Activity Involving the Upregulation of GluA1 and NR2A in Post-synaptic Densities

662 | Feb 15 2019

Zhang Y et al. suggested it would be detrimental to use the drug in seizure patients and might cause neuronal hyperexcitability in non-epileptic individuals. [Read the Full Post]

Upregulation of hydroxysteroid sulfotransferase 2B1b promotes hepatic oval cell proliferation by modulating oxysterol-induced LXR activation in a mouse model of liver injury

0 | Feb 12 2019

Wang Z et al. indicated that upregulation of SULT2B1b might promote HOC proliferation and aggravate liver injury via the suppression of oxysterol-induced LXR activation in chemically induced mouse liver injury. [Read the Full Post]

In vivo activation of invariant natural killer T cells induces systemic and local alterations in T-cell subsets prior to preterm birth

753 | Feb 11 2019

Gomez-Lopez N et al. found that iNKT-cell activation altered the systemic and local T-cell subsets prior to preterm labour/birth; however, treatment with rosiglitazone partially reversed such effects. [Read the Full Post]

Targeting the epigenome: Screening bioactive compounds that regulate histone deacetylase activity

0 | Jan 30 2019

Godoy LD et al. provided the first step in identifying multiple bioactive compound HDAC inhibitors. [Read the Full Post]

Dipeptidyl Peptidase-4 Induces Aortic Valve Calcification by Inhibiting Insulin-Like Growth Factor-1 Signaling in Valvular Interstitial Cells

747 | Jan 16 2019

Choi B et al. suggested that DPP-4 could serve as a potential therapeutic target to inhibit calcific aortic valve disease progression. [Read the Full Post]

Sildenafil suppresses the proliferation and enhances the apoptosis of hemangioma endothelial cells

547 | Jan 13 2019

He X et al. indicated the present study concluded that PDE-5 may be a potential therapeutic target for hemangiomas and Id-1 may serve a vital role in the associated signaling transduction pathways. [Read the Full Post]

Inhibition of related JAK/STAT pathways with molecular targeted drugs shows strong synergy with ruxolitinib in chronic myeloproliferative neoplasm

1222 | Jan 08 2019

Barrio S et al. showed the combination of ruxolitinib with inhibitors that target these pathways has a strong synergistic effect, which may be due to decreased activation of the common effector, STAT5. [Read the Full Post]

Low-Dose Farnesyltransferase Inhibitor Suppresses HIF-1α and Snail Expression in Triple-Negative Breast Cancer MDA-MB-231 Cells In Vitro

692 | Jan 05 2019

Tanaka T et al. suggested that FTIs may be capable of ameliorating the aggressive phenotype of TNBC by suppressing the HIF-1α-Snail pathway. [Read the Full Post]

Inhibition of the Pentose-phosphate Pathway Selectively Sensitizes Leukemia Lymphocytes to Chemotherapeutics by ROS-independent Mechanism

0 | Jan 05 2019

Zhelev Z et al. suggested that 6-ANA could be used as a supplementary component in anticancer chemotherapy, and would allows therapeutic doses of anticancer drugs to be reduced, thereby minimizing their side-effects. [Read the Full Post]

Synergistic Cytotoxicity of Melatonin and New-generation Anticancer Drugs Against Leukemia Lymphocytes But Not Normal Lymphocytes

0 | Jan 04 2019

Zhelev Z et al. suggested that melatonin is a promising supplementary component in chemotherapy which allows the therapeutic doses of anticancer drugs to be reduced, minimizing their side-effects. [Read the Full Post]

Cell-based assay system for high-throughput screening of anti-photo-aging agents in fibroblast transfectants

0 | Jan 03 2019

Lee S et al. indicated sclareol attenuated UVB-induced photo-aging by an increase in collagen synthesis and decrease in MMP-1 activity. [Read the Full Post]

PPARβ/δ, a Novel Regulator for Vascular Smooth Muscle Cells Phenotypic Modulation and Vascular Remodeling after Subarachnoid Hemorrhage in Rats

1594 | Dec 27 2018

Zhang H et al. identified PPARβ/δ as a useful regulator for VSMC phenotypic switch and vascular remodeling following SAH, providing novel insights into the therapeutic strategies of delayed cerebral ischemia. [Read the Full Post]

The antibiotic polymyxin B exhibits novel antifungal activity against Fusarium species

0 | Dec 23 2018

Hsu LH et al. found that PMB was fungicidal against all 12 Fusarium strains, with minimum fungicidal concentrations of 32 µg/mL or 64 µg/mL for most strains tested, as evidenced by broth dilution, methylene blue staining and XTT reduction assays. PMB can reduce the germination rates of conidia, but not chlamydospores, and can cause defects in cell membrane integrity in Fusarium strains. [Read the Full Post]

Cell-based assay system for high-throughput screening of anti-photo-aging agents in fibroblast transfectants

0 | Dec 21 2018

Lee S et al. revealed that CCN1-GFs treated with sclareol showed decreased levels of UVB-induced CCN1 expression. [Read the Full Post]

Microengineered cultures containing human hepatic stellate cells and hepatocytes for drug development

688 | Dec 16 2018

Davidson MD et al. found that NADPH oxidase (NOX) inhibition and farnesoid X receptor (FXR) activation using clinically relevant drugs alleviated hepatic dysfunctions in MPTCs. In conclusion, MPTCs recapitulate symptoms of NASH- and early fibrosis-like dysfunctions in PHHs and have utility for drug discovery in this space. [Read the Full Post]

FAM83A is amplified and promotes cancer stem cell-like traits and chemoresistance in pancreatic cancer

1253 | Dec 15 2018

Chen S et al. indicated that FAM83A has a vital oncogenic role to promote pancreatic cancer progression and may represent a potential clinical target. [Read the Full Post]

PPARβ/δ activation protects against corticosterone-induced ER stress in astrocytes by inhibiting the CpG hypermethylation of microRNA-181a

1642 | Dec 10 2018

Ji J et al. suggested that PPARβ/δ activation in astrocytes might be a promising target for regulating ER stress-induced astrocytic injury. [Read the Full Post]

A sensitive virus yield assay for evaluation of Antivirals against Zika Virus

0 | Nov 26 2018

Goebel S et al. indicated that due to reproducible assay performance, qPCR associated higher sensitivity and short duration of the assay time, this novel cell based assay will be very useful for confirming the activity of antivirals against ZIKV. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

0 | Nov 24 2018

SiRNAs that selectively reduced CSLC only were found to target genes for cholesterol and unsaturated fatty acid synthesis. [Read the Full Post]

N-3 polyunsaturated fatty acids increase hepatic fibroblast growth factor 21 sensitivity via a PPAR-γ-β-klotho pathway

0 | Nov 15 2018

Yang W et al. indicated n-3 PUFAs increase hepatic FGF21 sensitivity and β-klotho expression probably through a PPAR-γ-dependent mechanism, and may thereby exert hepatic beneficial effects on lipid metabolism. [Read the Full Post]

Identification of the Serine Biosynthesis Pathway as a Critical Component of BRAF Inhibitor Resistance of Melanoma, Pancreatic, and Non-Small Cell Lung Cancer Cells

1048 | Nov 08 2018

The novel aspects of this study are the direct identification of serine biosynthesis as a critical mechanism of BRAF V600E inhibitor resistance and the first successful example of using gemcitabine + BRAFis in combination to kill previously drug-resistant cancer cells, creating the translational potential of pretreatment with gemcitabine prior to BRAFi treatment of tumor cells to reverse resistance within the mutational profile and the WT. [Read the Full Post]

Btk inhibition treats TLR7/IFN driven murine lupus

768 | Oct 23 2018

Bender AT et al. provided translational insight into how Btk inhibition may provide benefit to a variety of SLE patients by affecting both BCR and FcR signaling. [Read the Full Post]

A sensitive virus yield assay for evaluation of Antivirals against Zika Virus

862 | Oct 15 2018

Goebel S et al. showed qPCR associated higher sensitivity and short duration of the assay time, this novel cell based assay will be very useful for confirming the activity of antivirals against ZIKV. [Read the Full Post]

A multi-targeted liquid chromatography-mass spectrometry screening procedure for the detection in human urine of drugs non-prohibited in sport commonly used by the athletes

901 | Oct 09 2018

Mazzarino M et al. indicated this work presents an analytical method for the simultaneous analysis in human urine of 38 pharmacologically active compounds (19 benzodiazepine-like substances, 7 selective serotonin reuptake inhibitors, 4 azole antifungal drugs, 5 inhibitors of the phosphodiesterases type 4 and 3 inhibitors of the phosphodiesterase type 5) by liquid-chromatography coupled with tandem mass spectrometry. [Read the Full Post]

The phosphodiesterase 4 inhibitor roflumilast augments the Th17-promoting capability of dendritic cells by enhancing IL-23 production, and impairs their T cell stimulatory activity due to elevated IL-10

629 | Oct 08 2018

Bros M et al. suggested that PDE4 inhibitors aside from their broad overall anti-inflammatory effects may enhance the Th17-polarizing capacity in DCs as an unwanted side effect. [Read the Full Post]

Synergistic cytotoxicity of BIIB021 with triptolide through suppression of PI3K/Akt/mTOR and NF-κB signal pathways in thyroid carcinoma cells

3370 | Oct 07 2018

Kim SH et al. suggested that BIIB021 has a cytotoxic activity accompanied by regulation of hsp90 client proteins in thyroid carcinoma cells. Moreover, the synergism between BIIB021 and triptolide in induction of cytotoxicity is associated with the inhibition of PI3K/Akt/mTOR and NF-κB signal pathways, the underexpression of survivin and the activation of DNA damage response in thyroid carcinoma cells. [Read the Full Post]

Targeting the epigenome: Screening bioactive compounds that regulate histone deacetylase activity

924 | Sep 26 2018

Godoy LD et al. provided the first step in identifying multiple bioactive compound HDAC inhibitors. Taken together, this report sets the stage for future exploration of these bioactive compounds as epigenetic regulators to potentially ameliorate chronic disease. [Read the Full Post]

Androgen Deprivation Followed by Acute Androgen Stimulation Selectively Sensitizes AR-Positive Prostate Cancer Cells to Ionizing Radiation

831 | Sep 22 2018

Hedayati M et al. suggested a potential cooperative effect and improved tumor growth delay with androgen-induced DSBs and radiation with implications for improving the therapeutic index of prostate cancer radiation therapy. [Read the Full Post]

Short-term high-fat feeding induces islet macrophage infiltration and β-cell replication independently of insulin resistance in mice

908 | Sep 21 2018

Woodland DC et al. suggested the existence of MΦ-mediated mechanisms in β-cell replication that are independent of insulin resistance. [Read the Full Post]

Neuregulin 1-activated ERBB4 interacts with YAP to induce Hippo pathway target genes and promote cell migration

788 | Sep 21 2018

Haskins JW et al. suggested that NRG1-ERBB4-YAP signaling contributes to the aggressive behavior of tumor cells. [Read the Full Post]

Integrated analysis of transcriptomes of cancer cell lines and patient samples reveals STK11/LKB1-driven regulation of cAMP phosphodiesterase-4D

700 | Sep 20 2018

He N et al. showed that multidimensional analysis of a well-characterized large-scale panel of cancer cell lines provides unprecedented opportunities for the identification of unexpected oncogenic mechanisms and mutation-specific drug targets. [Read the Full Post]

SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway

0 | Sep 20 2018

Wang J et al. demonstrated that SIRT1 and its activator, RSV, have clear anti-hyperuricemia functions in this mouse model. [Read the Full Post]

Kaempferol suppresses lipid accumulation by inhibiting early adipogenesis in 3T3-L1 cells and zebrafish

1261 | Sep 16 2018

Lee YJ et al. indicated that kaempferol might have an anti-obesity effect by regulating lipid metabolism. [Read the Full Post]

Luteinizing Hormone Causes Phosphorylation and Activation of the cGMP Phosphodiesterase PDE5 in Rat Ovarian Follicles, Contributing, Together with PDE1 Activity, to the Resumption of Meiosis.

667 | Sep 15 2018

Egbert JR et al. showed that activities of both PDE5 and PDE1 contribute to the LH-induced resumption of meiosis in rat oocytes, and that phosphorylation and activation of PDE5 is a regulatory mechanism. [Read the Full Post]

The LXR ligand GW3965 inhibits Newcastle disease virus infection by affecting cholesterol homeostasis

752 | Sep 13 2018

Sheng XX et al. suggested that GW3965 inhibits NDV infection, probably by affecting cholesterol homeostasis. [Read the Full Post]

Resveratrol provides neuroprotection by inhibiting phosphodiesterases and regulating the cAMP/AMPK/SIRT1 pathway after stroke in rats

837 | Sep 10 2018

Wan D et al. indicated that resveratrol provides neuroprotection by inhibiting PDEs and regulating the cAMP/AMPK/SIRT1 pathway, which reduces ATP energy consumption during ischemia. [Read the Full Post]

The anti-inflammatory effects of Morin hydrate in atherosclerosis is associated with autophagy induction through cAMP signaling

716 | Sep 10 2018

Zhou Y et al. suggested that anti-AS and anti-inflammatory effects of MO are largely associated with its induction of autophagy through stimulation of cAMP-PKA-AMPK-SIRT1 signaling pathway. [Read the Full Post]

The antibiotic polymyxin B exhibits novel antifungal activity against Fusarium species

777 | Aug 31 2018

Hsu LH et al. indicated evolutionary divergence of mechanisms between yeast pathogens and the filamentous fungus Fusarium. [Read the Full Post]

A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient

0 | Aug 27 2018

Chang JB et al. showed a significant variation among the Hill coefficients, suggesting a similar variation in therapeutic windows among anticoagulants in our assay. [Read the Full Post]

A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells

767 | Aug 07 2018

Lo Cicero A et al. highlight the potential of high-throughput drug screening using HGPS iPS-derived cells, in order to find therapeutic compounds for HGPS and, potentially, for other aging-related disorders. [Read the Full Post]

ICAM-1-Targeted Liposomes Loaded with Liver X Receptor Agonists Suppress PDGF-Induced Proliferation of Vascular Smooth Muscle Cells

843 | Jul 16 2018

Huang X et al. identified anti-ICAM-T0901317 liposomes as a promising nanotherapeutic approach to overcome VSMC proliferation during atherosclerosis progression. [Read the Full Post]

Inhibiting GLUT-1 expression and PI3K/Akt signaling using apigenin improves the radiosensitivity of laryngeal carcinoma in vivo

873 | Jun 19 2018

Bao YY et al. suggested that the effects of apigenin on inhibiting xenograft growth and enhancing xenograft radiosensitivity may be associated with suppressing the expression of GLUT-1 via the PI3K/Akt pathway. In addition, apigenin may enhance the effects of GLUT-1 AS-ODNs via the same mechanism. [Read the Full Post]

N-3 polyunsaturated fatty acids increase hepatic fibroblast growth factor 21 sensitivity via a PPAR-γ-β-klotho pathway

2919 | Jun 11 2018

Yang W et al. indicated n-3 PUFAs increase hepatic FGF21 sensitivity and β-klotho expression probably through a PPAR-γ-dependent mechanism, and may thereby exert hepatic beneficial effects on lipid metabolism. [Read the Full Post]

The non-Geldanamycin Hsp90 inhibitors enhanced the antifungal activity of fluconazole

1659 | Jun 09 2018

Li L et al. showed that the activity of FLC against C. albicans biofilm formation in vitro is significantly enhanced when used in combination with HSP990. [Read the Full Post]

A screening assay for the identification of host cell requirements and antiviral targets for hepatitis D virus infection

1145 | Jun 08 2018

Buchmann B et al. provided a potentially useful tool to screen for substances with anti-HDV activity and novel insights into interactions between HDV replication and the human kinome. [Read the Full Post]

WIP1 modulates responsiveness to Sonic Hedgehog signaling in neuronal precursor cells and medulloblastoma

1236 | Jun 02 2018

Wen J et al. suggested an important cross-talk between SHH and WIP1 pathways that accelerates tumorigenesis and supports WIP1 inhibition as a potential treatment strategy for MB. [Read the Full Post]

Androgen deprivation therapy sensitizes triple negative breast cancer cells to immune-mediated lysis through androgen receptor independent modulation of osteoprotegerin

867 | May 22 2018

Kwilas AR et al. supported the consideration of AR inhibition therapy for the treatment of AR- TNBC, especially in combination with cancer immunotherapy, providing a potential novel therapeutic option for select patients. [Read the Full Post]

Resveratrol Attenuates Aβ25-35 Caused Neurotoxicity by Inducing Autophagy Through the TyrRS-PARP1-SIRT1 Signaling Pathway.

834 | May 19 2018

Deng H et al. found that RSV attenuated neurotoxicity caused by Aβ25-35 through inducing autophagy in PC12 cells, and the autophagy was partially mediated via activation of the TyrRS-PARP1-SIRT1 signaling pathway. [Read the Full Post]

Dihydroartemisinin restricts hepatic stellate cell contraction via an FXR-S1PR2-dependent mechanism

918 | May 09 2018

Xu W et al. suggested that DHA could restrict HSC contraction through modulating FXR/S1PR2 pathway-mediated Ca(2+) -dependent and Ca(2+) -sensitization signaling. Our discoveries make DHA a potential candidate for portal hypertension. [Read the Full Post]

PPARβ/δ activation protects against corticosterone-induced ER stress in astrocytes by inhibiting the CpG hypermethylation of microRNA-181a

2374 | May 06 2018

Ji J et al. suggested that PPARβ/δ activation in astrocytes might be a promising target for regulating ER stress-induced astrocytic injury. [Read the Full Post]

Lipopolysaccharide and heat stress impair the estradiol biosynthesis in granulosa cells via increase of HSP70 and inhibition of smad3 phosphorylation and nuclear translocation

1770 | May 01 2018

Li H et al. suggested that LPS and heat stress could impair estradiol biosynthesis in GCs via increased HSP70 and indirect inhibition of Smad3 phosphorylation and nuclear translocation. [Read the Full Post]

Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer

1047 | Apr 30 2018

Li J et al. demonstrated a new strategy for treating metastatic pancreatic cancer by inhibiting cholesterol esterification. [Read the Full Post]

PPARβ/δ activation protects against corticosterone-induced ER stress in astrocytes by inhibiting the CpG hypermethylation of microRNA-181a

932 | Apr 27 2018

Ji J et al. suggested that PPARβ/δ activation in astrocytes might be a promising target for regulating ER stress-induced astrocytic injury. [Read the Full Post]

Activation of carbonic anhydrase IX by alternatively spliced tissue factor under late-stage tumor conditions.

916 | Apr 21 2018

Ramchandani D et al. found that CAIX is a novel downstream mediator of asTF in pancreatic cancer, particularly under hypoxic conditions that model late-stage tumor microenvironment. [Read the Full Post]

Tanshinone I inhibits tumor angiogenesis by reducing Stat3 phosphorylation at Tyr705 and hypoxia-induced HIF-1α accumulation in both endothelial and tumor cells

838 | Apr 12 2018

Wang Y et al. revealed unique characteristics of tanshinone-1 and its improved derivatives as promising angiogenesis inhibitors. [Read the Full Post]

Neuroprotective effects of piperine on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease mouse model.

0 | Apr 06 2018

Yang W et al. showed that piperine exerts a protective effect on dopaminergic neurons via antioxidant, anti-apoptotic, and anti-inflammatory mechanisms in an MPTP-induced mouse model of PD [Read the Full Post]

Tsc1 expression by dendritic cells is required to preserve T-cell homeostasis and response

0 | Mar 28 2018

Luo Y et al. identified Tsc1 as a crucial signaling checkpoint in DCs essential for preserving T-cell homeostasis and response. [Read the Full Post]

Significance of alpha smooth muscle actin expression in traumatic painful neuromas: a pilot study in rats

989 | Mar 28 2018

Weng W et al. provided new insights into the development of new treatment modalities for the management of intractable painful neuromas. [Read the Full Post]

Characterization of osimertinib (AZD9291)-resistant non-small cell lung cancer NCI-H1975/OSIR cell line

1753 | Mar 03 2018

Tang ZH et al. showed that EGFR could pose as one of the OSI-resistant mechanisms and navitoclax might be the candidate drug for OSI-resistant NSCLC patients. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

1724 | Feb 19 2018

Song M, et al. provided a useful resource that can be exploited for the selective elimination of CSLCs. [Read the Full Post]

Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner

875 | Feb 15 2018

Xu W et al. indicated DHA significantly improved alcoholic liver injury by inhibiting hepatic steatosis, which was dependent on its activation of FXR in hepatocytes. [Read the Full Post]

Histochemical examination of the effects of high-dose 1,25(OH)2D3 on bone remodeling in young growing rats

910 | Feb 13 2018

Sun J et al. suggested that long-term use of physiologically-high dose calcitriol may result in bone loss through RANKL/RANK/osteoprotegerin and EphrinB2-EphB4 signaling pathways, and that these negative effects could continue after drug withdrawal. Therefore, optimal limits for vitamin D administration need to be established for children and adolescents. [Read the Full Post]

Fasting-induced hormonal regulation of lysosomal function.

0 | Feb 12 2018

Chen L et al. indicated the FGF21-TFEB signaling axis links lysosome homeostasis with extracellular hormonal signaling to orchestrate lipid metabolism during fasting. [Read the Full Post]

FOXM1 evokes 5-fluorouracil resistance in colorectal cancer depending on ABCC10

847 | Feb 07 2018

Xie T et al. suggested that FOXM1/ABCC10 axis may serve as a potential therapeutic target for 5-FU resistance in CRC patients. [Read the Full Post]

Efficacy of continuous EGFR-inhibition and role of Hedgehog in EGFR acquired resistance in human lung cancer cells with activating mutation of EGFR

0 | Jan 20 2018

Della Corte CM et al. found that EGFR-mutant NSCLC can benefit from continuous treatment with EGFR-inhibitors, indepenently from mechanisms of resistance [Read the Full Post]

Epigallocatechin gallate reverses cTnI-low expression-induced age-related heart diastolic dysfunction through histone acetylation modification

2481 | Jan 11 2018

Pan B et al. provided new insights into histone acetylation mechanisms of EGCG treatment that may contribute to the prevention of CDD in ageing populations. [Read the Full Post]

Simvastatin augments revascularization and reperfusion in a murine model of hind limb ischemia - Multimodal imaging assessment

924 | Jan 09 2018

Goggi JL et al. identified using 99mTc-RGD SPECT, which displays significant increases in retention before macrovascular volume changes are measureable with MRI. [Read the Full Post]

BCL6 modulation of acute lymphoblastic leukemia response to chemotherapy

1481 | Dec 27 2017

Slone WL et al. suggested that BCL6 is one factor, modulated by microenvironment derived cues that may contribute to regulation of ALL therapeutic response. [Read the Full Post]

CK2α' Drives Lung Cancer Metastasis by Targeting BRMS1 Nuclear Export and Degradation

0 | Dec 02 2017

Liu Y et al. identified a therapeutically exploitable posttranslational mechanism by which CK2α-mediated degradation of BRMS1 promotes metastases in lung cancer. [Read the Full Post]

HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death

1952 | Nov 29 2017

Jacobsen AV et al. implicated HSP90 as a modulator of necroptosis at the level of MLKL, a function that complements HSP90's previously demonstrated modulation of the upstream necroptosis effector kinases, RIPK1 and RIPK3. [Read the Full Post]

The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms

2125 | Nov 25 2017

Paraiso KH et al.showed that HSP90 inhibition may be a highly effective strategy at managing the diverse array of resistance mechanisms being reported to BRAF inhibitors and appears to be more effective at restoring BIM expression and downregulating Mcl-1 expression than combined MEK/PI3K inhibitor therapy. [Read the Full Post]

Hsp90β promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma

1967 | Nov 24 2017

Meng J et al. investigated the correlation between Hsp90β expression and CD31+ endothelial cell-dependent vessel density. [Read the Full Post]

HSP90 Shapes the Consequences of Human Genetic Variation

0 | Nov 14 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis

2619 | Oct 16 2017

Zhang F et al. provided evidence that the canonical hedgehog pathway controlled HSC-mediated liver angiogenesis. Selective inhibition of HSC hedgehog signalling could be a promising therapeutic approach for hepatic fibrosis. [Read the Full Post]

Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer

1148 | Oct 10 2017

Ju HQ et al. suggested that Nampt inhibition may override gemcitabine resistance by decreasing the NAD level and suppressing glycolytic activity, warranting further clinical investigation for pancreatic cancer treatment. [Read the Full Post]

HSP90 Shapes the Consequences of Human Genetic Variation

0 | Sep 26 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

HSP90 Shapes the Consequences of Human Genetic Variation

2174 | Sep 25 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

Inhibition of glioblastoma cell proliferation, migration and invasion by the proteasome antagonist carfilzomib

1897 | Sep 22 2017

Areeb Z et al. showed that carfilzomib represents a novel, yet FDA-approved agent for the treatment of glioblastoma multiforme. [Read the Full Post]

A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes

1200 | Sep 21 2017

Qian XJ et al. suggested that SZA potently inhibited pan-HCV genotype entry into hepatoma cells and primary human hepatocytes without interfering virus binding on cell surface or internalization. However, virion-cell fusion process was impaired in the presence of SZA, along with the increased host membrane fluidity. We also found that SZA inhibited the spread of HCV to the neighboring cells, and combinations of SZA with interferon or telaprevir resulted in additive synergistic effect against HCV. Additionally, SZA diminished the establishment of HCV infection in vivo. The SZA target is different from conventional direct-acting antiviral agents, therefore, SZA is a potential therapeutic compound for the development of effective HCV entry inhibitors, especially for patients who need to prevent HCV reinfection during the course of liver transplantations. [Read the Full Post]

Hyperthermia reduces migration of osteosarcoma by suppression of autocrine motility factor

2151 | Sep 09 2017

Nakajima K et al. indicated hyperthermia reduced AMF expression and tumor cell motility via HSP27 and may therefore be applied as osteosarcoma treatment. [Read the Full Post]

Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism

1561 | Jun 21 2017

Yang W, et al. used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile, to treat melanoma in mice and observed a good antitumour effect. [Read the Full Post]

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

0 | Jun 05 2017

Gillan V et al. provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

Phosphodiesterase 5/protein kinase G signal governs stemness of prostate cancer stem cells through Hippo pathway

1140 | Jun 01 2017

Liu N et al. suggested that PDE5 inhibitors in combination with chemotherapeutic agents could effectively prevent initiation, metastasis, and relapse of prostate cancer. [Read the Full Post]

The effect of hyperlipidemia on the pharmacokinetics, hepatic and pulmonary uptake of posaconazole in rat

0 | May 20 2017

Khalil HA et al. induced lipoprotein level elevation caused alterations in the PSZ pharmacokinetics and decreased its hepatic and pulmonary uptake. [Read the Full Post]

Neuritin Mediates Activity-Dependent Axonal Branch Formation in Part via FGF Signaling.

4381 | May 07 2017

Shimada T et al suggested that neuritin and FGF cooperate in inducing mossy fiber sprouting through FGF signaling. Together, these results suggest that FGF and neuritin-mediated axonal branch induction are involved in the aggravation of epilepsy. [Read the Full Post]

Specificity of anti-prostate cancer CYP17A1 inhibitors on androgen biosynthesis

1280 | Apr 08 2017

Udhane SS et al. concluded that orteronel is a highly specific inhibitor of 17,20 lyase activity. [Read the Full Post]

A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition

2577 | Apr 06 2017

Kim H et al. demonstrated that CX-4945 is a potent DYRK1A inhibitor and also suggested that it has therapeutic potential for DYRK1A-associated diseases. [Read the Full Post]

A Repurposing Strategy for Hsp90 Inhibitors Demonstrates Their Potency against Filarial Nematodes

1 | Mar 27 2017

Gillan V et al provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

The-cyclic-GMP-protein-kinase-G-pathway-as-a-therapeutic-target-in-head-and-neck-squamous-cell-carcinoma

1258 | Mar 19 2017

Tuttle TR et al found that Tadalafil substantially reduced the growth of CAL27-derived tumors in athymic mice. Several drugs which either activate sGC or inhibit PDE5 are approved for treatment of nonmalignant conditions. These drugs could be repurposed as novel and effective therapeutics in patients with head and neck cancer. [Read the Full Post]

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ

3028 | Mar 16 2017

Zhao D et al found that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ. [Read the Full Post]

Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner

2335 | Mar 14 2017

Huyan T et al. suggested that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy. [Read the Full Post]

SIRT1 prevents hyperuricemia via the PGC-1α/PPARγ-ABCG2 pathway

1502 | Mar 09 2017

Wang J et al. found that one possible mechanism is the activation of ABCG2 in the ileum through the PGC-1α/PPARγ pathway. [Read the Full Post]

In vitro antifungal synergy between amphiphilic aminoglycoside K20 and azoles against Candida species and Cryptococcus neoformans

0 | Mar 07 2017

Shrestha SK et al. suggested that combinations of K20 and azoles offer a possible strategy for developing therapies against candidiasis. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

0 | Feb 04 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

4977 | Jan 29 2017

Gillan V et al. provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

0 | Jan 26 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

Pioglitazone Suppresses CXCR7 Expression To Inhibit Human Macrophage Chemotaxis through Peroxisome Proliferator-Activated Receptor γ

1551 | Jan 23 2017

Zhao D, et al.'s data demonstrate that pioglitazone suppresses CXCR7 expression to inhibit human macrophage chemotaxis through PPARγ. [Read the Full Post]

Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner

2333 | Jan 22 2017

Huyan T, et al.'s findings suggest that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy. [Read the Full Post]

In vitro antifungal synergy between amphiphilic aminoglycoside K20 and azoles against Candida species and Cryptococcus neoformans

1539 | Jan 18 2017

Shrestha SK et al. suggested that combinations of K20 and azoles offer a possible strategy for developing therapies against candidiasis. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

2759 | Jan 01 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

The cyclic GMP/protein kinase G pathway as a therapeutic target in head and neck squamous cell carcinoma

0 | Sep 04 2016

Tuttle TR, et al. found that several drugs which either activate sGC or inhibit PDE5 are approved for treatment of nonmalignant conditions. These drugs could be repurposed as novel and effective therapeutics in patients with head and neck cancer. [Read the Full Post]

An unusual mechanism of ERBB4 in regulating tumor related gene expression

9832 | Jan 06 2015

Haskins et al. found ERBB4 activated the transcriptional coactivator YAP by binding to its ligand neuregulin 1 (NRG1), to regulate gene expression of cancer cells. [Read the Full Post]

ERK/Cdk5 axis regulates diabetes-related PPARγ phosphorylation

8327 | Nov 21 2014

Recently, Banks et al. discovered that ERK/Cdk5 axis is involved in regulation PPARγ activities, and the inhibition of ERK and MEK leads to the improvement of insulin resistance. [Read the Full Post]

AGI5198 is the first highly potent and selective mutant IDH1 inhibitor

3854 | Mar 07 2014

AGI-5198, potently inhibits mutant IDH1 (R132H-IDH1 and R132C-IDH1), but not wildtype IDH1 (IC50 > 100 μM) or any of IDH2 isoforms (R140Q, R172K, wildtype) (IC50 > 100 μM) [Read the Full Post]

Gsk256066 is a potent and selective inhaled PDE4 inhibitor

2797 | Jan 24 2014

GSK256066 is a selective PDE4B(equal affinity to isoforms A-D) inhibitor with IC50 of 3.2 pM, >380,000-fold selectivity versus PDE1/2/3/5/6 and >2500-fold selectivity against PDE4B versus PDE7. [Read the Full Post]

Tipifarnib is a farnesyltransferase inhibitor

3127 | Dec 18 2013

Tipifarnib (R115777) is a potent and specific farnesyltransferase (FTase) inhibitor with IC50 of 0.6 nM, its anti-proliferative effects are most prominent in H-ras or N-ras mutant cells. [Read the Full Post]

FK866 has been shown to induce apoptosis by non competitive

3372 | Nov 12 2013

APO866 effectively inhibits nicotinamide phosphoribosyltransferase (NMPRTase) with IC50 of 0.09 nM. Phase 1/2. [Read the Full Post]

Learn about the prescription medication Methazolamide

3066 | May 26 2013

Methazolamide is a carbonic anhydrase inhibitor with Ki of 50 nM, 14 nM and 36 nM for hCA I, hCA II and bCA IV isoforms, respectively. [Read the Full Post]

Effects of oral administration of methazolamide on intraocular pressure

3011 | May 22 2013

In vitro characterization of the erythrocyte distribution of methazolamide: a model of erythrocyte transport and binding kinetics [Read the Full Post]

LY2484595 is one of two CETP inhibitors currently being evaluated

3079 | May 02 2013

LY2484595 results in 98.4%, 98.6%, and 18.4% inhibition of CETP activity at 4 hours, 8 hours and 24 hours post dose respectively in human ApoAI and CETP double transgenic mice. [Read the Full Post]

MDV3100 was found clinically active for metastatic

2968 | Apr 18 2013

MDV3100 is an androgen receptor antagonist drug developed by the pharmaceutical company Medivation for the treatment of metastatic castration-resistant prostate cancer. [Read the Full Post]

Enzalutamide is an androgen receptor inhibitor

2531 | Feb 27 2013

Little is known of pathways involved in upstream control of Notch1 gene expression and activity in keratinocytes, and mammalian cells in general. To address this issue we undertook a chemical genetics approach. Rather than screening a large collection of unknown chemicals, enzalutamide we chose a library of 489 compounds [Read the Full Post]

MDV3100 is an androgen receptor antagonist

2645 | Jan 15 2013

Increased protein levels and kinase activities of Src family kinases have been observed in a wide diversity of human cancers, including melanoma, breast, ovarian, and lung cancer . The prototype SFK is c-Src, MDV3100 which is a protein tyrosine kinase from which the oncogenic viral Src is derived . [Read the Full Post]

ONCOGENES AND HSP90 INHIBITORS

5366 | Aug 24 2012

PATHWAY OF HSP90 AND CANCER CELL LINES: Heat shock protein 90 or Hsp90 is actually a non-fibrous protein which gained its name from its molecular weight that is 90kDa. Hsp90 is most abundant cytoplasmic protein which plays a significant role in cells by acting like a molecular chaperone for many proteins related to some important signaling cascades of the cell. Different proteins chaperones that are existing in the cell, involve serine/theronine kinases and tyrosine kinases as well hence they are very much important for the proper regulation of cell growth and cell cycle. A detailed research is carried out to describe the relation between Hsp90 and cancers. To inhibit this chaperone i.e. Hsp90, the simple strategy of designing Hsp protein inhibitor was developed when Hsp90 was found to be existing in different cancerous cell lines activated through the activation of oncogenes. It has been proved a very fruitful therapy for cancer. [Read the Full Post]

HSP90 INHIBITORS AND ONCOGENES

5772 | Aug 16 2012

HSP90 CASCADE AND CANCER CELLS: Hsp90 or the Heat shock protein 90 is a non fibrous protein that gained its name on the basis of its molecular weight i.e., 90kDa. Heat shock protein 90 is the most abundant protein present in cytoplasm that plays a significant role in the cells by acting as molecular chaperones for different proteins associated with some important signaling pathways in the cells. Various molecular chaperones existing in the cells, involves in the tyrosine kinases and serine/theronine kinases as well, so they are very important for proper regulation of cell cycle and cell growth. A complete research has been done to describe the relation between cancer and Hsp90. For the inhibition of Hsp90 chaperone a simple strategy is designed i.e., development of Hsp-60 inhibitor in case of presence of Hsp90 in the cancerous cells and activated by the activation of various oncogenes. It was proved to be an efficient therapy for the treatment of cancer. [Read the Full Post]

HSP90 INHIBITORS AND ONCOGENES

5510 | Aug 02 2012

HSP90 PATHWAY AND CANCER CELLS: Heat shock protein 90 or Hsp90 is a non-fibrous protein that has gained its name from its 90kDa molecular weight. This is the most abundant protein present in cytoplasm and plays an important role in the cell by acting as a chaperone for many of the proteins involved in important signaling pathways of the cell. There are various proteins chaperones which are present in the cell, includes TKs or tyrosine kinases and theronine/serine kinases as well and these are very important for the regulation of cell cycle and growth. Detailed research has been conducted to connect cancers and Hsp90. As Hsp90 has shown by different cancerous cells which are activated via activating oncogenes a simple strategy for the inhibition of this chaperone has developed by designing Hsp90 inhibitors. This approach has been fruitful for cancer therapy. [Read the Full Post]

HSP INHIBITORS AGAINST PROTEIN FOLDING

4578 | Mar 19 2012

Introduction: Cellular Quality Assurance The network of chemical reactions linked to the mechanisms behind cellular growth, proliferation and differentiation are complex. Referred to as biochemical pathways these mechanisms operate on some simple principles starting with the receipt of a message from the host system to the cell itself. The pathway system can be likened to a production line facility with the product being a normal health cell. So mechanisms exists for stock piling of raw materials, for the synthesis of component parts, for the recycling of waste materials, for the removal of unwelcome molecules, quality assurance and final product viability. One the key aspects of cellular growth is the delicacy of the whole process, it does not take much to drive a mechanism off balance and produce a faulty product, to ensure quality under stress induced conditions a series of proteins exist referred to as Heat Shock Proteins that assess the quality of proteins being constructed for cell growth purposes. [Read the Full Post]

TOSEDOSTAT: INHIBITING AMINOPEPTIDASES IN CANCERS

3585 | Mar 18 2012

AMINOPEPTIDASES AND THEIR INHIBITION: Aminopeptidases catalyze the cleavage of amino acids of proteins or peptide substrates. Such enzymes are zinc dependant and located throughout most mammalian tissue and in certain plant extracts. They are essential for many cellular maintenance functions and are release systemically from the small intestine. Since these enzymes act by hydrolysis amino acids located at the amino groups of terminal proteins inhibition of their processes would affect cell proliferation, secretion, invasion and angiogenesis. Small molecule inhibitors for the inhibition of aminopeptidases have been developed for oncological use. CHR-2797 is a pro-drug for an aminopeptidase inhibitor that is marketed by Chroma Therapeutics under the trade name of Tosedostat. Tosedostat aminopeptidase inhibitor under goes cellular modulation to the active metabolite (CHR79888) via hydrolysis of a methoxy group. This metabolite is poorly membrane permeable, resulting in cellular accumulation. In animal models Toseostad has proved to be a significant inhibitor of proliferation and has demonstrated anti-angiogenic activity. [Read the Full Post]

Roles of Hsp90 in wound healing and cancer

5962 | Oct 24 2011

Wound healing is an intricate process in which the skin (or another organ-tissue) repairs itself after injury. At present, local growth factors are considered to be the driving force for wound healing and only recombinant human platelet-derived growth factor-BB (PDGF-BB) has been approved by US FDA for topical treatment of diabetic ulcers. However, the use of PDGF-BB in clinical trials has been limited for its modest efficacy, high cost and risk of causing cancer. Thus, novel treatment for wound healing is needed to be explored. [Read the Full Post]

Chiosis, G., M. Vilenchik, et al. (2004). "Hsp90: the vulnerable chaperone." Drug Discov Today 9(20): 881-888.

4442 | Apr 19 2011

Agents that interact with its C-terminus or modify its post-translational status represent additional ways of interfering with chaperone activity. This review will discuss several emerging classes of Hsp90 inhibitors and their modes of action. [Read the Full Post]