Neuronal Signaling

ROCK Inhibitors as an Alternative Therapy for Corneal Grafting: A Systematic Review

843 | Feb 15 2024

The review on ROCK inhibitors for corneal wound healing showcases their diverse therapeutic potential across various ocular conditions, offering promise as an effective alternative to human donor tissue for addressing the significant unmet medical need in corneal blindness. [Read the Full Post]

Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia

248 | Feb 15 2024

The MuSICAL screening strategy efficiently identified a potentially effective triple combination therapy for paediatric AML using FDA-approved compounds, showcasing promising avenues for rapid clinical translation and therapeutic advancements. [Read the Full Post]

Proteomic and Phosphoproteomic Profiling Reveals the Oncogenic Role of Protein Kinase D Family Kinases in Cholangiocarcinoma

654 | Feb 15 2024

The comprehensive analysis of protein and phosphorylation signatures in cholangiocarcinoma revealed the PRKD family's pivotal role, highlighting their potential as novel treatment targets validated by the inhibitory effects of 1-naphthyl PP1 on CCA cell proliferation, migration, and invasion. [Read the Full Post]

Exploration of a new class of monoamine oxidase B inhibitors by assembling benzyloxy pharmacophore on halogenated chalcones

119 | Feb 14 2024

BB2 and BB4, derivatives of benzyloxy-derived halogenated chalcones, exhibit potent, selective, and reversible inhibition of MAO-B, marking them as promising drug candidates for treating neurodegenerative disorders like Parkinson's disease. [Read the Full Post]

Protective Role of Ethanol Extract of Cibotium barometz (Cibotium Rhizome) against Dexamethasone-Induced Muscle Atrophy in C2C12 Myotubes

188 | Feb 14 2024

This study demonstrates the potential of Cibotium Rhizome extract (ECR) in mitigating dexamethasone-induced muscle atrophy by modulating key proteins involved in muscle growth and atrophy pathways in C2C12 myotubes, offering a promising avenue for developing therapeutic agents against conditions like sarcopenia. [Read the Full Post]

Vestibular Testing-New Physiological Results for the Optimization of Clinical VEMP Stimuli

217 | Feb 12 2024

The review explores the intricate synaptic and receptor mechanisms of auditory and vestibular systems, proposing an "ultrafast" non-quantal transmission as the cause of rapid vestibular afferent responses, with profound implications for clinical testing and understanding neural processing in these sensory pathways. [Read the Full Post]

Hippocampal CaMKII inhibition induces reactivation-dependent amnesia for extinction memory and causes fear relapse

101 | Feb 11 2024

Inhibition of hippocampal CaMKII activity post-fear extinction memory recall in rats disrupts extinction consolidation, facilitating GluN2B-NMDAR-dependent fear recovery, underscoring CaMKII's pivotal role in fear memory reconsolidation. [Read the Full Post]

The role of glutamate NMDA receptors of the mediodorsal thalamus in scopolamine-induced amnesia in rats

153 | Feb 11 2024

This study demonstrates that activation of glutamate NMDA receptors in the mediodorsal thalamus mitigates scopolamine-induced memory impairment, while their blockade exacerbates this cognitive deficit, suggesting a pivotal role for the MD glutamatergic system via the NMDA receptor pathway in memory consolidation. [Read the Full Post]

Inhibition of striatal dopamine release by the L-type calcium channel inhibitor isradipine co-varies with risk factors for Parkinson's

141 | Feb 11 2024

The study elucidates that L-type voltage-gated calcium channels (LTCCs) govern dopamine release in a regionally and sexually divergent manner, influenced by multiple factors associated with either increased vulnerability or protection against Parkinson's disease. [Read the Full Post]

Ecological benefits of artificial light at night (ALAN): Accelerating the development and metamorphosis of marine shellfish larvae

221 | Feb 10 2024

The comprehensive study on artificial light at night (ALAN) reveals a surprising positive impact of short-wavelength blue light on Pacific abalone embryonic development, offering crucial insights into the differential effects of light spectrums and their implications for marine benthic ecosystems. [Read the Full Post]

Sibutramine-Induced Nonischemic Cardiomyopathy

236 | Feb 09 2024

The case report of sibutramine-induced nonischemic cardiomyopathy in a young individual underscores the critical need for safer anti-obesity medications and vigilant patient monitoring to mitigate severe cardiovascular risks associated with pharmacotherapy. [Read the Full Post]

DHA and EPA Alleviate Epileptic Depression in PTZ-Treated Young Mice Model by Inhibiting Neuroinflammation through Regulating Microglial M2 Polarization and Improving Mitochondrial Metabolism

172 | Feb 07 2024

The study's findings highlight the potential of EPA and DHA supplementation as effective interventions to alleviate depressive symptoms in pediatric patients with epilepsy, with EPA demonstrating particularly favorable effects by mitigating neuronal degeneration, reducing neuroinflammation, and modulating oxidative stress through distinct molecular mechanisms. [Read the Full Post]

Content of amino acids and biogenic amines in stored meat as a result of a broiler diet supplemented with β-alanine and garlic extract

204 | Feb 07 2024

Supplementing chicken feed with garlic extract and β-alanine showed promise in increasing protein content, altering amino acid levels, and potentially reducing biogenic amine formation, improving the quality and shelf life of poultry meat during storage. [Read the Full Post]

CYP-catalysed Cycling of Clozapine and Clozapine- N-oxide Promotes the Generation of Reactive Oxygen Species in vitro

332 | Feb 06 2024

This study reveals that specific CYP isoforms, particularly CYP3A4, not only drive clozapine metabolism to its major metabolites but also link to the formation of reactive species, potentially underpinning clozapine-induced toxicity in treatment-resistant schizophrenia. [Read the Full Post]

Suggestion of creatine as a new neurotransmitter by approaches ranging from chemical analysis and biochemistry to electrophysiology

175 | Feb 05 2024

The identification of creatine within synaptic vesicles and its demonstrated impact on neuronal function suggests its potential role as a novel neurotransmitter, marking a significant advancement in understanding brain physiology and potential implications for neurological disorders. [Read the Full Post]

Integrative Pharmacology in the Treatment of Substance Use Disorders

159 | Feb 05 2024

Navigating the intricate web of neurobiological pathways, an integrated approach targeting KYNA-NMDA-α7nAChRcentric pathophysiology presents a promising avenue for developing novel combination treatments to address substance use disorders comprehensively. [Read the Full Post]

Optimization of anesthetic procedure in crustaceans: Evidence for sedative and analgesic-like effect of MS-222 using a semi-automated device for exposure to noxious stimulus

152 | Feb 02 2024

This study demonstrates the efficacy of MS-222 as an anesthetic in Gammarus pulex while introducing a novel semi-automated electric shock device for assessing nociceptive responses in aquatic invertebrates, highlighting its potential for standardized research protocols in this field. [Read the Full Post]

C5 methylation confers accessibility, stability and selectivity to picrotoxinin

243 | Feb 02 2024

Exploring minor modifications in picrotoxinin analogs revealed that a C5 methyl group significantly altered channel selectivity between mammalian and insect ion channels, pioneering the first systematic structure-activity relationship studies for picrotoxinin while highlighting the impact of subtle structural changes on functional properties. [Read the Full Post]

A Randomized Controlled Trial of a Novel Formulation of Ketorolac Tromethamine for Continuous Infusion (NTM-001) in Healthy Volunteers

150 | Feb 01 2024

The study's findings indicate that NTM-001, administered as a 12.5 mg IV bolus followed by continuous infusion, aligns closely with predicted pharmacokinetic parameters, demonstrating potential as a safe and effective nonopioid alternative for acute postoperative pain control. [Read the Full Post]

Polyamine metabolism and glutamate receptor agonists-mediated excitotoxicity in the rat brain

246 | Jan 28 2024

The study compared various glutamate receptor agonists' impact on inducing excitotoxic brain damage in rats, revealing PUT as a potential general marker of such damage due to its concurrent increase with brain injury following both ionotropic and metabotropic glutamate receptor activation. [Read the Full Post]

Role of ON and OFF Visual Pathways in Rod- and Cone-Driven Flicker Responses

273 | Jan 28 2024

The study identified distinct neurotransmitter effects on rod and cone-driven flicker responses, emphasizing the involvement of ON and OFF visual pathways, horizontal cells, and the sensitivity of low-frequency flicker in ophthalmic pathophysiological research. [Read the Full Post]

Vascular injury associated with ethanol intake is driven by AT1 receptor and mitochondrial dysfunction

116 | Jan 19 2024

Ethanol-induced vascular dysfunction involves a cascade of events including RAAS activation, mitochondrial impairment, increased mtROS, reduced nitric oxide and hydrogen peroxide bioavailability, findings that offer potential therapeutic strategies for disorders linked to excessive ethanol consumption. [Read the Full Post]

Lyophilization enhances the stability of Panax notoginseng total saponins-loaded transfersomes without adverse effects on ex vivo/in vivo skin permeation

195 | Jan 13 2024

Lyophilized Panax notoginseng saponin-loaded transfersomes (PNS-FD-TFSs) exhibit enhanced stability while preserving transdermal absorption, offering a promising advancement in drug delivery systems. [Read the Full Post]

Altered brain serotonin 5-HT1A receptor expression and function in juvenile Fmr1 knockout mice

145 | Jan 09 2024

The study's findings on 5-HT1A receptor expression and responsiveness to agonists in juvenile Fmr1 knockout mice suggest a promising therapeutic potential of 5-HT1AR agonists for managing auditory hypersensitivity and seizures in young individuals with Fragile X syndrome. [Read the Full Post]

Active natural compounds perturb the melanoma risk-gene network

376 | Jan 07 2024

The study ingeniously employs network modeling of melanoma-associated genes, revealing crucial pathways and potential therapeutic targets while showcasing the predictive potential of this model in evaluating the efficacy of anti-melanoma phytochemicals. [Read the Full Post]

Fabrication and characterization of dihydromyricetin-loaded microcapsules stabilized by glyceryl monostearate and whey protein-xanthan gum

267 | Jan 02 2024

Encapsulation of dihydromyricetin using glyceryl monostearate and octyl/decyl glycerate as inner cores, whey protein, and xanthan gum as wall materials demonstrated enhanced stability, controlled release, and improved antioxidant effects, presenting a promising strategy for delivering lipophilic bioactive compounds with heightened bioavailability and stability. [Read the Full Post]

Puerarin ameliorates myocardial remodeling of spontaneously hypertensive rats through inhibiting TRPC6-CaN-NFATc3 pathway

191 | Dec 25 2023

Puerarin administration in spontaneously hypertensive rats demonstrated significant improvements in cardiac function and myocardial structure, potentially mediated by its inhibition of the TRPC6-CaN-NFATc3 pathway, suggesting promise for Puerarin as a therapeutic intervention in hypertensive myocardial remodeling. [Read the Full Post]

Safety comparisons among monoamine oxidase inhibitors against Parkinson's disease using FDA adverse event reporting system

109 | Dec 23 2023

Understanding the distinct adverse event profiles among MAO-B inhibitors like selegiline, rasagiline, and safinamide illuminates nuanced differences in their safety profiles, aiding clinicians in personalized Parkinson's disease management. [Read the Full Post]

In vitro antineoplastic effects of MK0752 in HPV-positive head and neck squamous cell carcinoma

262 | Dec 19 2023

The study demonstrates the potential therapeutic efficacy of the gamma-secretase inhibitor MK0752 in head and neck squamous cell carcinoma, particularly inducing apoptosis in human-papillomavirus-positive tumors, suggesting its viability as a targeted treatment option pending further validation and mechanistic exploration. [Read the Full Post]

Pharmacological Modulation of the Ca2+/cAMP/Adenosine Signaling in Cardiac Cells as a New Cardioprotective Strategy to Reduce Severe Arrhythmias in Myocardial Infarction

252 | Dec 18 2023

The study demonstrates that blocking L-type Ca2+ channels attenuates cardiac arrhythmias induced by acute myocardial infarction, implicating the Ca2+/cAMP/adenosine signaling pathway as a promising therapeutic target to reduce severe and fatal arrhythmias in humans. [Read the Full Post]

Assessment of the effects of Syk and BTK inhibitors on GPVI-mediated platelet signaling and function

0 | Dec 17 2023

The study shows that small molecule tyrosine kinase inhibitors targeting Syk and BTK effectively inhibit essential platelet functions, such as adhesion, secretion, and aggregation, but exhibit differential effects on downstream signaling pathways and protein activities in platelets. [Read the Full Post]

Simufilam Reverses Aberrant Receptor Interactions of Filamin A in Alzheimer's Disease

123 | Dec 16 2023

Simufilam disrupts aberrant FLNA-receptor interactions in Alzheimer's disease, preventing Aβ42 signaling, tau hyperphosphorylation, and inflammatory responses, thereby promoting brain health and potentially offering a promising treatment approach for the condition. [Read the Full Post]

Dual action of serotonin on local excitatory and inhibitory neural circuits regulating the corticotropin-releasing factor neurons in the paraventricular nucleus of the hypothalamus

107 | Dec 16 2023

Serotonin modulates corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus by upregulating glutamatergic interneurons via 5-HT7 receptors and downregulating GABAergic interneurons via 5-HT2C receptors, as demonstrated in an electrophysiological study using the CRF-modified yellow fluorescent protein (Venus) ΔNeo mouse model. [Read the Full Post]

Simulated microgravity-induced oxidative stress and loss of osteogenic potential of osteoblasts can be prevented by protection of primary cilia

181 | Dec 09 2023

Microgravity-induced shortening of primary cilia triggers overexpression and hyperactivity of TRPV4 channels, leading to intracellular Ca2+ overload, oxidative stress, and loss of osteogenic potential in osteoblasts, a process preventable by protecting primary cilia. [Read the Full Post]

Theophylline-induced endothelium-dependent vasodilation is mediated by increased nitric oxide release and phosphodiesterase inhibition in rat aorta

212 | Dec 06 2023

Theophylline-induced endothelium-dependent vasodilation in isolated rat thoracic aortas is mediated by increased endothelial nitric oxide release, guanylate cyclase activation, elevated cGMP levels, and enhanced endothelial nitric oxide synthase phosphorylation. [Read the Full Post]

Cuminum cyminum Ameliorates Urotoxic Effects of Cyclophosphamide by Modulating Antioxidant, Inflammatory Cytokines, and Urinary Bladder Overactivity: In vivo and In Silioc investigations

128 | Dec 02 2023

The study demonstrates that the aqueous ethanol extract of Cuminum cyminum attenuates cyclophosphamide-induced bladder toxicity in rats by reducing oxidative stress, inflammation, and smooth muscle overactivity, while in silico analysis identifies potential bioactive compounds for future drug development. [Read the Full Post]

Identification of potential RapJ hits as sporulation pathway inducer candidates in Bacillus coagulans via structure-based virtual screening and molecular dynamics simulation studies

304 | Dec 01 2023

Computational analyses identified acarbose as a potential inhibitor of the RapJ enzyme, crucial for inducing the sporulation pathway in Bacillus coagulans, but experimental validation is necessary to confirm its effectiveness. [Read the Full Post]

TRUST-II: a global phase II study of taletrectinib in ROS1-positive non-small-cell lung cancer and other solid tumors

188 | Nov 29 2023

TRUST-II is a global phase II study evaluating taletrectinib's efficacy and safety in treating ROS1+ non-small-cell lung cancer and other ROS1+ solid tumors, with confirmed objective response rate as the primary endpoint and secondary endpoints including duration of response, progression-free survival, overall survival, and safety assessments, enrolling patients across North America, Europe, and Asia to address unmet needs in overcoming resistance, treating brain metastasis, and reducing neurological side effects. [Read the Full Post]

Microglia trigger the structural plasticity of GABAergic neurons in the hippocampal CA1 region of a lipopolysaccharide-induced neuroinflammation model

164 | Nov 26 2023

The study demonstrates that LPS-induced microglial activation in the hippocampal CA1 region leads to cognitive impairment through the upregulation of GABAergic inhibitory synapses, and this effect can be reversed by blocking GABA receptor activity or depleting microglia, highlighting the critical role of neuroinflammatory responses and synaptic plasticity in cognitive dysfunction. [Read the Full Post]

Revisiting matrix hydrogel composed of gelatin and hyaluronic acid and its application in cartilage regeneration

189 | Nov 25 2023

The biomacromolecule-based bioadhesive matrix hydrogel, composed of methacrylate gelatin and modified hyaluronic acid, demonstrates promising potential for cartilage repair by promoting tissue integration, supporting chondrogenesis of stem cells, and enhancing articular cartilage regeneration in knee osteoarthritis. [Read the Full Post]

High-intensity interval training improves fatty infiltration in the rotator cuff through the β3 adrenergic receptor in mice

201 | Nov 25 2023

High-Intensity Interval Training (HIIT) improved muscle quality in a rotator cuff tear model by activating the β3 adrenergic receptor pathway, enhancing supraspinatus muscle function, and reducing atrophy and fatty infiltration. [Read the Full Post]

Spinal cannabinoid receptor 2 activation alleviates neuropathic pain by regulating microglia and suppressing P2X7 receptor

185 | Nov 19 2023

The study demonstrates that continuous activation of cannabinoid receptor 2 (CB2R) with the specific agonist PM226 promotes a neuroprotective transition in microglia, attenuates neuropathic pain, and reduces proinflammatory P2X7 receptor content, offering a potential therapeutic avenue for managing neuropathic pain with low abuse potential. [Read the Full Post]

Atypical Acetylcholine Receptors on the Neurons of the Turkish Snail

271 | Nov 17 2023

The study on Helix lucorum snail neurons demonstrated that their nicotinic acetylcholine receptors (nAChRs) exhibit a complex and atypical pharmacological profile, responding to various nAChR ligands and muscarinic receptor ligands, with α7, muscle-type, and α9 nAChRs playing key roles in mediating acetylcholine-induced depolarization. [Read the Full Post]

Nuciferine protects against lipopolysaccharide-induced endometritis via inhibiting ferroptosis and modulating AMPKα/mTOR/HIF-1α signaling axis

213 | Nov 16 2023

Nuciferine (NF) demonstrates protective effects against lipopolysaccharide (LPS)-induced endometritis in mice by modulating multiple pathways, including MyD88/NF-κB, MAPK, ferroptosis, and the AMPKα/mTOR/HIF1α signaling axis, while also exerting direct anti-inflammatory effects in endometrial epithelial cells through the inhibition of the NF-κB signaling pathway. [Read the Full Post]

Icariside II induces rapid phosphorylation of endothelial nitric oxide synthase via multiple signaling pathways

75 | Nov 13 2023

Icariside II stimulates the rapid phosphorylation of eNOS at Ser1177 and Thr495 through multiple signaling pathways, leading to increased eNOS expression and nitric oxide release in human umbilical vein endothelial cells (HUVECs), suggesting its potential therapeutic relevance in conditions related to endothelial dysfunction. [Read the Full Post]

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

351 | Nov 11 2023

In this hypothetical scenario, researchers have identified ACSS2 as a key regulator of alkaliptosis, a pH-dependent cell death process, and its manipulation holds promise as a potential therapeutic strategy for pancreatic ductal adenocarcinoma (PDAC) treatment. [Read the Full Post]

Combined inhibition of aurora kinases and Bcl-xL induces apoptosis through select BH3-only proteins

0 | Nov 08 2023

The study demonstrates that combining small-molecule inhibitors of AURK with BH3-mimetic inhibitors targeting Bcl-xL potently induces apoptosis and may overcome resistance to AURK inhibitors in colon cancer cells. [Read the Full Post]

Design, synthesis and anti-Chikungunya virus activity of lomerizine derivatives

163 | Nov 01 2023

The study demonstrated that Lomerizine (Lom) and its derivatives exhibited potent anti-CHIKV activity and low cytotoxicity, particularly compounds B1 and B7, suggesting their potential as effective anti-Chikungunya drugs. [Read the Full Post]

Role of P2X7R in eosinophilic and non‑eosinophilic chronic rhinosinusitis with nasal polyps

135 | Oct 30 2023

The study found that P2X7R is overexpressed in chronic rhinosinusitis with nasal polyps (CRSwNP), and its activation mediates NLRP3 inflammasome activation, suggesting its potential role in the pathogenesis of CRSwNP. [Read the Full Post]

Bioengineered stem cell membrane functionalized nanoparticles combine anti-inflammatory and antimicrobial properties for sepsis treatment

257 | Oct 27 2023

The novel nanometer drug loading system, FZ/MER-AgMOF@Bm, effectively combats sepsis by delivering anti-inflammatory and antibacterial agents to infectious microenvironments, reducing inflammation, eliminating bacteria, and improving survival outcomes in a mouse model of sepsis. [Read the Full Post]

Agomelatine inhibits platelet aggregation through melatonin receptor-dependent and independent mechanisms

203 | Oct 25 2023

In this study, agomelatine was found to inhibit platelet aggregation induced by arachidonic acid and collagen, suggesting its potential to prevent atherothrombotic ischemic events by reducing thrombus formation and vessel occlusion. [Read the Full Post]

Neuropeptide Y1 receptor antagonism protects β-cells and improves glycemic control in type 2 diabetes

136 | Oct 22 2023

The study identified increased expression of the neuropeptide Y1 receptor in human islets from subjects with type 2 diabetes, which was associated with reduced insulin secretion, and demonstrated that treatment with the Y1 receptor antagonist BIBO3304 improved beta-cell function, preserved beta-cell mass, and resulted in better glycemic control in mouse models of type 2 diabetes. [Read the Full Post]

Improvement of the functional value of green soybean (edamame) using germination and tempe fermentation: A comparative metabolomics study

176 | Oct 18 2023

This study demonstrated that tempe fermentation significantly increased the concentrations of important bioactive metabolites in green soybean, thereby highlighting its potential to improve the functionality of this legume. [Read the Full Post]

Transcranial direct current stimulation attenuates chronic pain in knee osteoarthritis by modulating BDNF/TrkB signaling in the descending pain modulation system

142 | Oct 12 2023

This hypothetical study suggests that upregulation of the BDNF/TrkB signaling in the descending pain modulation system may be involved in chronic pain associated with knee osteoarthritis (KOA) in rats, and transcranial direct current stimulation (tDCS) may alleviate this pain by inhibiting the BDNF/TrkB signaling pathway. [Read the Full Post]

Current Treatments for Patients with Genetic Obesity

314 | Oct 10 2023

Genetic obesities, characterized by impaired central control of body weight and a predominant genetic contribution, require a comprehensive approach that combines lifestyle interventions with individualized care based on genetic diagnosis to effectively manage the condition and improve quality of life. [Read the Full Post]

The protective effects of NE 52-QQ57 against interleukin-33-induced inflammatory response in activated synovial mast cells

535 | Oct 09 2023

The study suggests that inhibiting GPR4 signaling with the antagonist NE 52-QQ57 may have therapeutic benefits in rheumatoid arthritis by reducing inflammatory responses and oxidative stress in synovial mast cells. [Read the Full Post]

The purinergic receptors 2X3 on spiral ganglion neurons enhance the medial olivocochlear reflex in mice after long-term moderate noise exposure

198 | Oct 07 2023

Long-term moderate noise exposure increases the expression of P2X3 receptors in spiral ganglion neurons (SGNs) and enhances the medial olivocochlear (MOC) reflex, which can be downregulated by AF-353, a specific antagonist for P2X3 receptors. [Read the Full Post]

Olanzapine With or Without Fosaprepitant for Preventing Chemotherapy Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: A Phase III Randomized, Double-Blind, Placebo-Controlled Trial (ALLIANCE A221602)

121 | Oct 04 2023

The clinical trial comparing an olanzapine-based antiemetic regimen with and without an NK-1 receptor antagonist did not demonstrate sufficient evidence to support the removal of the NK-1 receptor antagonist for preventing chemotherapy-induced nausea and vomiting. [Read the Full Post]

[Therapeutic drug monitoring of antipsychotic drugs in routine psychiatric practice]

319 | Oct 01 2023

This study examined the relationship between daily doses of antipsychotic drugs, their serum concentrations, and patient characteristics in the treatment of schizophrenia, highlighting the importance of therapeutic drug monitoring and individual patient factors on drug exposure. [Read the Full Post]

Phospholipase D2 targeted by miR-5132-5p alleviates cerulein-induced acute pancreatitis via the Nrf2/NFκB pathway

299 | Sep 19 2023

The study revealed that phospholipase D2 (PLD2), targeted by microRNA-5132-5p (miR-5132-5p), can attenuate cerulein-induced acute pancreatitis in AR42J cells by modulating the Nrf2/NFκB pathway, highlighting its potential as a therapeutic target for AP. [Read the Full Post]

Switch type I to type II TRK inhibitors for combating clinical resistance induced by xDFG mutation for cancer therapy

237 | Aug 16 2023

Compound 12d demonstrated potent inhibitory activity against various TRK fusion proteins, including those associated with acquired resistance to first-generation inhibitors, suggesting its potential as a lead compound for the treatment of TRK-driven cancers. [Read the Full Post]

BDNF and its signaling in cancer

0 | Aug 16 2023

BDNF signaling plays a significant role in cancer progression, and targeted therapies aimed at inhibiting BDNF and its associated pathways hold promise as potential therapeutic approaches. [Read the Full Post]

Involvement of a flavoprotein, acetohydroxyacid synthase, in growth and riboflavin production in riboflavin-overproducing Ashbya gossypii mutant

339 | Aug 16 2023

This study demonstrates that branched-chain amino acids, particularly through the regulation of acetohydroxyacid synthase, play a crucial role in enhancing riboflavin production in the Ashbya gossypii mutant strain, offering a novel approach for optimizing riboflavin production in this organism. [Read the Full Post]

Pharmacological Inventions for Alzheimer Treatment in the United States of America: A Revision Patent from 2010 - 2020

80 | Aug 14 2023

The study analyzed pharmacological treatments for Alzheimer's disease protected in the US Patent Office, revealing a focus on targeting Aβ accumulation and the need for further research to establish the efficacy of the patented molecules. [Read the Full Post]

A high-concentrate diet induces inflammatory injury via regulating Ca2+/CaMKKβ-mediated autophagy in mammary gland tissue of dairy cows

210 | Jul 26 2023

The study found that a high-concentrate diet induced autophagy in mammary gland tissue through the Ca2+/CaMKKβ-AMPK signaling pathway, leading to inflammatory injury in dairy cows. [Read the Full Post]

Melatonin promotes orofacial antinociception in adult zebrafish by modulating TRP channels

265 | Jul 20 2023

Melatonin demonstrated an orofacial antinociceptive effect in adult zebrafish, which was associated with the modulation of TRP channels, particularly TRPV1. [Read the Full Post]

Divergent splanchnic sympathetic efferent nerve pathways regulate interleukin-10 and tumour necrosis factor-α responses to endotoxaemia

325 | Jul 19 2023

This study demonstrates that the splanchnic sympathetic nerves mediate an endogenous neural reflex that enhances interleukin-10 levels and suppresses tumor necrosis factor-α levels in response to systemic immune challenge, with distinct pathways regulating these cytokine responses. [Read the Full Post]

Novel hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine show collateral sensitivity in multidrug-resistant glioblastoma cells

175 | Jul 13 2023

This study describes the synthesis and evaluation of hybrid molecules combining sclareol and synthetic 1,2,4-triazolo[1,5-a]pyrimidines, resulting in compounds with improved cytotoxic properties, selectivity towards glioblastoma cells, and evasion of multidrug resistance. [Read the Full Post]

MDR1 Inhibition Reverses Doxorubicin-Resistance in Six Doxorubicin-Resistant Canine Prostate and Bladder Cancer Cell Lines

179 | Jul 13 2023

This study generated doxorubicin-resistant sublines of canine prostate adenocarcinoma and urothelial cell carcinoma cell lines, identifying drug efflux via MDR1 overexpression as a common mechanism, and suggesting the use of MDR1 inhibitors and combination therapies to address acquired chemoresistance. [Read the Full Post]

Case Report: Identification of a novel NTRK3-AJUBA fusion co-existing with ETV6-NTRK3 fusion in papillary thyroid carcinoma

328 | Jul 08 2023

This study reports the identification of a novel NTRK3-AJUBA fusion co-existing with a known ETV6-NTRK3 fusion in thyroid cancer, expanding the spectrum of translocation partners and highlighting the importance of further investigation regarding the impact of dual NTRK3 fusion on TRK inhibitor therapy and prognosis. [Read the Full Post]

Larotrectinib versus historical standard of care in patients with infantile fibrosarcoma: protocol of EPI-VITRAKVI

341 | Jul 08 2023

The EPI VITRAKVI study is a retrospective study that compares the time to medical treatment failure between larotrectinib and chemotherapy in patients with infantile fibrosarcoma using external historical controls and adjusting for potential confounding using the Inverse Probability of Treatment Weighting method. [Read the Full Post]

Lymphatic-draining nanoparticles deliver Bay K8644 payload to lymphatic vessels and enhance their pumping function

151 | Jul 06 2023

This study showed that formulating S-(-)-Bay K8644 (BayK) within lymph-draining nanoparticles (NPs) improved lymphatic vessel function and effectively treated lymphatic dysfunction, providing a promising therapeutic approach. [Read the Full Post]

Synthesis and Preclinical Positron Emission Tomography Imaging of the p38 MAPK Inhibitor [11C]Talmapimod: Effects of Drug Efflux and Sex Differences

172 | Jun 27 2023

The development of the first positron emission tomography (PET) radiotracer for imaging MAPK p38α/β, synthesized through radiolabeling the inhibitor talmapimod with carbon-11, showed promising results but faced challenges regarding its non-displaceable binding and P-gp efflux. [Read the Full Post]

Characterization of Potent ABCG2 Inhibitor Derived from Chromone: From the Mechanism of Inhibition to Human Extracellular Vesicles for Drug Delivery

136 | Jun 27 2023

This study characterizes a potent ABCG2 inhibitor, C4a, and demonstrates its selectivity and efficacy in inhibiting ABCG2-mediated drug efflux, utilizing liposomes and extracellular vesicles for improved delivery and highlighting the potential of plasma circulating EVs as a drug delivery system for hydrophobic drugs targeting membrane proteins. [Read the Full Post]

Late sodium current in synergism with Ca2+/calmodulin-dependent protein kinase II contributes to β-adrenergic activation-induced atrial fibrillation

246 | Jun 08 2023

Late INa and CaMKII play important roles in β-adrenergic stimulation-induced atrial fibrillation, and the inhibition of both can exert synergistic anti-arrhythmic effects. [Read the Full Post]

Protein kinase D1 promotes the survival of random-pattern skin flaps in rats

244 | May 28 2023

The study demonstrated that PKD1 improves skin flap survival by promoting angiogenesis, reducing oxidative stress, and inhibiting apoptosis and inflammation, suggesting it as a potential therapeutic target for flap failure treatment. [Read the Full Post]

Renal tubular epithelial cells treated with calcium oxalate up-regulate S100A8 and S100A9 expression in M1-polarized macrophages via interleukin 6

150 | May 23 2023

This study demonstrates that M1-polarized macrophages are the main source of S100A8 and S100A9 in the kidneys of nephrolithiasis patients, and that COM-induced IL6 secretion from renal tubular epithelial cells can up-regulate their expression in macrophages. [Read the Full Post]

Regulation of neuropathic pain by microglial Orai1 channels

179 | May 14 2023

The study found that Orai1 channels are key regulators of microglial reactivity in neuropathic pain, with sex-specific effects observed in female mice. [Read the Full Post]

Rimegepant 75 mg in Subjects With Hepatic Impairment: Results of a Phase 1, Open-Label, Single-Dose, Parallel-Group Study

115 | May 10 2023

The study found that rimegepant is not recommended for use in adults with severe hepatic impairment due to a significant increase in systemic exposure observed in this population. [Read the Full Post]

Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: A systematic review and network meta-analysis of the literature

127 | May 10 2023

The network meta-analysis found that all formulations of lasmiditan, rimegepant, and ubrogepant were superior in efficacy to placebo, with lasmiditan 200 mg being the most effective but associated with high rates of adverse events. [Read the Full Post]

LincRNA-p21 Promotes Cellular Senescence by Down-regulating the Wnt/β-catenin Pathway in MPP+-treated SH-SY5Y Cells

236 | May 07 2023

This study aimed to investigate the role of lincRNA-p21 in MPP+-induced senescence in SH-SY5Y cells and its potential as a therapeutic target for Parkinson's disease. [Read the Full Post]

Molecular Design of 68Ga- and 89Zr-Labeled Anticalin Radioligands for PET-Imaging of PSMA-Positive Tumors

342 | May 05 2023

The study demonstrates the potential of Anticalin proteins as radioligands for PET-imaging of xenograft tumors in mice, with the use of PASylation technology to tailor their plasma half-life and the cyclic radiochelator FsC being superior to Dfo for 89Zr-ImmunoPET-imaging. [Read the Full Post]

Antidepressant efficacy of cariprazine in bipolar disorder and the role of its pharmacodynamic properties: A hypothesis based on data

268 | May 04 2023

The study investigated whether the pharmacodynamic properties of cariprazine fit into a previously developed model for the treatment of bipolar depression, which was based on a combination of clinical and preclinical data, and found that its properties fit well with the proposed model, but further clarification is needed regarding its norepinephrine reuptake inhibition. [Read the Full Post]

Anti-Parkinson Effects of Holothuria leucospilota-Derived Palmitic Acid in Caenorhabditis elegans Model of Parkinson's Disease

178 | May 02 2023

The study found that HLEA-P3, a compound derived from the sea cucumber Holothuria leucospilota, composed of palmitic acid, showed potential anti-Parkinson effects in C. elegans models by restoring dopaminergic neurons, reducing oxidative stress, decreasing α-synuclein aggregation, and upregulating genes encoding antioxidant enzymes and autophagic mediators. [Read the Full Post]

4-octyl itaconate ameliorates alveolar macrophage pyroptosis against ARDS via rescuing mitochondrial dysfunction and suppressing the cGAS/STING pathway

309 | Apr 28 2023

This study suggests that 4-octyl itaconate has the potential to ameliorate acute respiratory distress syndrome by inhibiting NLRP3-mediated macrophage pyroptosis in a STING/IRF3-dependent manner and rescuing mitochondrial dysfunction. [Read the Full Post]

Randomised, prospective, blinded, clinical trial of opioid-free injectable anaesthesia with or without multimodal analgesia in kittens undergoing ovariohysterectomy

232 | Apr 27 2023

This study found that an opioid-free injectable anaesthetic protocol with multimodal analgesia provided effective pain relief and reduced the need for rescue analgesia in kittens undergoing ovariohysterectomy, while also observing a decrease in food intake due to pain. [Read the Full Post]

A Cardiologists' Survey on the Use of Anticoagulants and Antiplatelets in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Those Undergoing Percutaneous Coronary Intervention in India

339 | Apr 22 2023

The survey found that in India, the majority of cardiologists use triple therapy (NOAC + dual antiplatelet) or NOAC + single antiplatelet therapy to manage patients with AF and ACS or undergoing PCI, with NOACs being the preferred anticoagulant and ticagrelor and clopidogrel being the preferred P2Y12 inhibitors. [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]

Disruption of NOTCH signaling by a small molecule inhibitor of the transcription factor RBPJ

291 | Apr 17 2023

RBPJ Inhibitor-1 (RIN1) is a new class of small molecule inhibitor that disrupts the interaction between NOTCH and RBPJ, which can be exploited for chemical biology and therapeutic applications, and may lead to more specific and targeted therapies for diseases involving NOTCH signaling. [Read the Full Post]

Targeted inhibition of RBPJ transcription complex alleviates the exhaustion of CD8+ T cells in hepatocellular carcinoma

172 | Apr 17 2023

This study suggests that targeting the RBPJ transcription complex with a small molecule compound may be a promising strategy for immunotherapy of hepatocellular carcinoma by inhibiting the malignant behaviors of HCC cells and alleviating T cell exhaustion. [Read the Full Post]

A 2023 update on the advancements in the treatment of agitation in Alzheimer's disease

271 | Apr 16 2023

Recent advances in the understanding of neurobiological mechanisms of agitation in Alzheimer's Disease have led to the identification of several agents with promise for treating agitation, and clinical trials are underway to develop safe and efficacious treatment options. [Read the Full Post]

Clinical benefit of MAO-B and COMT inhibition in Parkinson's disease: practical considerations

248 | Apr 16 2023

MAO-B and COMT inhibitors are important strategies for managing motor fluctuations in Parkinson's disease patients, with several drugs available on the market targeting these enzymes, and ongoing studies exploring new formulations and combinations of these inhibitors. [Read the Full Post]

Association of reported NSAID adverse drug reactions with opioid prescribing following total joint arthroplasty

374 | Apr 14 2023

This retrospective cohort study found that reported adverse drug reactions to nonsteroidal anti-inflammatory drugs were associated with an increased risk of prolonged receipt of opioids following total joint arthroplasty. [Read the Full Post]

Targeting the Nerve Growth Factor Signaling Impairs the Proliferative and Migratory Phenotype of Triple-Negative Breast Cancer Cells

327 | Apr 11 2023

The study investigates the role of nerve growth factor and its receptor, tropomyosin receptor kinase A, in triple-negative breast cancer and suggests that targeting TrkA may be a potential therapeutic strategy for this disease. [Read the Full Post]

Hedgehog Signals Mediate Anti-Cancer Drug Resistance in Three-Dimensional Primary Colorectal Cancer Organoid Culture

364 | Mar 30 2023

The study suggests that targeting the Hedgehog signaling pathway and cancer stem cells using inhibitors like AY9944 and GANT61 can improve the sensitivity of anti-cancer drug treatment in colorectal tumor patient-derived ALI organoids and may be a useful combinational therapeutic strategy against metastatic colorectal cancer. [Read the Full Post]

Towards personalized treatment with clozapine

383 | Mar 30 2023

This study found that clozapine was more effective when used as a first- or second-line treatment, and identified factors associated with response to clozapine treatment and side effects, which could aid in the development of personalized treatment approaches for individuals with treatment-resistant schizophrenia. [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]

Preparation and evaluation of injectable microsphere formulation for longer sustained release of donepezil

222 | Mar 23 2023

The study developed an injectable formulation of donepezil using microspheres made of PLA or PLGA and a hydrogel wrapping, which showed sustained release and reduced inflammatory response compared to the PLGA microspheres alone. [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]

Mechanisms of paeoniaceae action as an antidepressant

217 | Mar 22 2023

Paeoniflorin (PF) has been shown to have multiple mechanisms through which it exerts its antidepressant effects, including increasing the levels of monoamine neurotransmitters, inhibiting the HPA axis, promoting neuroprotection, enhancing neurogenesis in the hippocampus, and elevating levels of BDNF. [Read the Full Post]

Involvement of the tuberomammillary nucleus of the hypothalamus in the modulation of nociception and joint edema in a model of monoarthritis

282 | Mar 15 2023

The study suggests that histaminergic projections from the TMN to the spinal cord play a role in the modulation of nociception and peripheral edema in a subacute monoarthritis model, and that the hypothalamus may trigger TMN activation via glutamate and orexin. [Read the Full Post]

Lorazepam in catatonia - Past, present and future of a clinical success story

188 | Mar 14 2023

This passage discusses the history, effectiveness, and potential future directions for the use of lorazepam in the treatment of catatonia, emphasizing the importance of empirical observation and clinical practice, while also calling for further scientific investigation. [Read the Full Post]

Pharmacokinetic and Pharmacodynamic Comparison of Fluticasone Propionate/Formoterol Fumarate Administered via a Pressurized Metered-Dose Inhaler and a Novel Breath-Actuated Inhaler in Healthy Volunteers

182 | Mar 13 2023

The passage describes the results of two studies comparing the exposure of fluticasone/formoterol following administration via BAI with pMDI with/without a spacer in healthy volunteers, which showed that BAI performance was comparable to pMDI and systemic safety with BAI was no worse than the primary comparator. [Read the Full Post]

Loss of TRPV4 Cation Channel Inhibition of Macrophage Infiltration and Neovascularization in a Mouse Cornea

253 | Mar 12 2023

This study shows that TRPV4 plays a role in injury-induced neovascularization in the corneal stroma and may be a potential therapeutic target to prevent unfavorable neovascularization post-injury. [Read the Full Post]

Electrochemically assisted production of biogenic palladium nanoparticles for the catalytic removal of micropollutants in wastewater treatment plants effluent

150 | Mar 11 2023

This work demonstrates the potential of biogenic palladium nanoparticles to remove persistent micropollutants from wastewater, with the size of the nanoparticles affecting their catalytic activity. [Read the Full Post]

Concentration dependence of active potassium transport in the human red blood cell in the presence of inhibitors

411 | Mar 09 2023

The passage describes the inhibition of active potassium influx in human red blood cells by several compounds, including strophanthidin, ethacrynic acid, and MK-870, and suggests a model for the behavior of the transport system in the presence of these compounds and potassium ions. [Read the Full Post]

Pro-myelinating Clemastine administration improves recording performance of chronically implanted microelectrodes and nearby neuronal health

321 | Mar 09 2023

Enhancing oligodendrocyte activity with the pharmaceutical drug Clemastine can prevent the chronic decline of microelectrode recording performance and improve the integration of functional device interfaces with brain tissue over a long period of time. [Read the Full Post]

Pharmacological treatment promoting remyelination enhances motor function after internal capsule demyelination in mice

283 | Mar 09 2023

This study suggests that the lysophosphatidylcholine-induced IC demyelination mouse model is useful for evaluating the effects of pharmacological treatments that promote remyelination on motor function and histological changes. [Read the Full Post]

Metabolic characterization and GAPDH dependent regulation of ENaC in hPheo1 wild-type and SDHB knockdown cells

289 | Mar 08 2023

The study investigates the expression and activity of ENaC and ASIC ion channels in hPheo1 WT and SDHB KD cells, which may provide important insights into understanding and treating SDHB-related disease. [Read the Full Post]

In vivo phenotypic validation of adenosine receptor-dependent activity of non-adenosine drugs

275 | Mar 07 2023

The study used mouse hypothermia as an in vivo screen for adenosinergic effects and identified several drugs that interact with adenosine receptors (ARs) in different ways, suggesting potential for repurposing and highlighting the importance of considering multiple mechanisms of action and potential off-target effects. [Read the Full Post]

Effects of atomoxetine plus a hypnotic on obstructive sleep apnea severity in patients with a moderately collapsible pharyngeal airway

224 | Mar 07 2023

The study found that the combination of atomoxetine and trazodone (Ato-Trazo) reduced obstructive sleep apnea severity without reducing the arousal threshold, but worsened subjective sleep quality. [Read the Full Post]

Solvent-Mediated Tunable Regiodivergent C6- and N1-Alkylations of 2,3-Disubstituted Indoles with p-Quinone Methides

196 | Mar 06 2023

A new method for regioselective alkylations of 2,3-disubstituted indoles with para-quinone methides using indium catalysts and solvents has been developed and can be selectively adjusted, scaled up, and applied to the late-stage functionalization of indomethacin with support from experimental and density functional theory studies. [Read the Full Post]

Electrospun nanofibers using β-cyclodextrin grafted chitosan macromolecules loaded with indomethacin as an innovative drug delivery system

158 | Mar 06 2023

The study developed a β-CD-g-CS nanofiber-based drug delivery system with sustained release of indomethacin and favorable physicomechanical properties and biocompatibility for use in orthopedic applications. [Read the Full Post]

The successful treatment of Enterocytozoon bieneusi Microsporidiosis with nitazoxanide in a patient with B-ALL: A Case Report

219 | Mar 01 2023

This case highlights the need to consider opportunistic infections in immunocompromised patients and the importance of using metagenomic sequencing in diagnosing such infections, as well as the limited available options for treating E. bieneusi infections and the need for further research. [Read the Full Post]

Addition of Nitazoxanide to Standard Clarithromycin Based Triple Therapy for 2 Weeks Effectively Eradicates Treatment-Naive Helicobacter Pylori Infection. A Single Centre prospective, open-label study

323 | Mar 01 2023

The NACE regimen (nitazoxanide, amoxicillin, clarithromycin, and esomeprazole) was found to be an effective and well-tolerated treatment for H. pylori infection, resulting in eradication in over 90% of patients in both per-protocol and intention to treat analyses. [Read the Full Post]

LY450139 Inhibited Ti-Particle-Induced Bone Dissolution via Suppressing Notch and NF-κB Signaling Pathways

282 | Feb 27 2023

The study found that LY450139 has the potential to prevent the failure of joint implants by inhibiting the formation of osteoclasts, which break down bone, through the inhibition of the NF-κB and Notch signaling pathways. [Read the Full Post]

Endothelial-specific targeting of RhoA signaling via CD31 antibody-conjugated nanoparticles

498 | Feb 26 2023

The study aimed to develop a CD31-targeting liposome with Fasudil, a clinically-relevant Rho kinase inhibitor, to target the RhoA signaling in endothelial cells for potential anti-angiogenic therapy by minimizing toxicity. [Read the Full Post]

Predictive factors for improvement of symptomatic cerebral vasospasm following subarachnoid hemorrhage by selective intra-arterial administration of fasudil hydrochloride

629 | Feb 26 2023

Selective intra-arterial administration of fasudil improves neurological findings in 72.2% of patients with cerebral vasospasm following subarachnoid hemorrhage and is most effective when the spasm is limited to peripheral vessels and the patient is younger and does not have a large cerebral infarction in the spasm artery perfusion area. [Read the Full Post]

CB2R activation ameliorates late adolescent chronic alcohol exposure-induced anxiety-like behaviors during withdrawal by preventing morphological changes and suppressing NLRP3 inflammasome activation in the microglia of the prefrontal cortex in mice

137 | Feb 25 2023

Chronic alcohol exposure in late adolescence increases anxiety-like behaviors by activating microglia in the prefrontal cortex, which can be prevented by activating the cannabinoid type 2 receptor through CB2R agonist treatment. [Read the Full Post]

Combinational Inhibition of P-Glycoprotein-Mediated Etoposide Transport by Zosuquidar and Polysorbate 20

181 | Feb 22 2023

The study found that while combination of zosuquidar and polysorbate 20 showed additive P-gp inhibition in vitro, oral etoposide bioavailability decreased when co-administered with both agents in vivo due to high level of nonspecific zosuquidar adsorption. [Read the Full Post]

The study of Raddeanin A cerebrovascular endothelial cell trafficking through P-glycoprotein

182 | Feb 22 2023

Raddeanin A, a natural triterpenoid, is transported through the brain-blood barrier by P-glycoprotein and its transport is affected by its expression and function, providing important guidance on its pharmacodynamic effect in human brains. [Read the Full Post]

Staurosporine analogues from microbial and synthetic sources and their biological activities

452 | Feb 20 2023

Staurosporine and its analogues have strong inhibitory effects against a variety of kinases and have various biological properties such as antifungal, antibacterial, and immunosuppressive activities, but have limited clinical effectiveness due to cross-reactivity and poor selectivity. [Read the Full Post]

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

832 | 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]

Roles of light transmission aggregometry and CYP2C19 genotype in predicting ischaemic complications during interventional therapy for intracranial aneurysms

315 | Feb 19 2023

The study concluded that maximum platelet aggregation induced by ADP (ADP-MPA) can predict ischaemic events during endovascular treatment of intracranial aneurysms and patients with flow diverters require stronger antiplatelet medication than patients with traditional stents. [Read the Full Post]

Long-term risk, clinical management, and healthcare resource utilization of stable patients with coronary artery disease and post-myocardial infarction in Greece-TIGREECE study

232 | Feb 19 2023

In Greece, one in ten patients experience a recurring cardiovascular event or death, mainly of ischemic origin, 1-3 years post myocardial infarction, according to results from the TIGREECE study. [Read the Full Post]

Can pharmaceutical pollution alter the spread of infectious disease? A case study using fluoxetine

276 | Feb 17 2023

Fluoxetine exposure affects the severity of a bacterial infection in water fleas in a non-monotonic manner, but the effect varies with both the infection outcome measured and the genotype of the pathogen, leading to complex genotype-by-environment interactions in its influence on disease dynamics. [Read the Full Post]

Crusted scabies in AIDS patient, a clinical challenge to be sorted out with a simple bedside test

394 | Feb 17 2023

A case of crusted scabies, a severe and highly contagious variant of scabies, was reported in an AIDS patient with hyperpigmented macules covered in thick crusts on the axilla, inguinal region, and gluteal region, and was treated with ivermectin, permethrin, and keratolytics after a KOH microscopy revealed a population of more than 1 million mites. [Read the Full Post]

A pilot study of chemotherapy combinations in rats: Focus on mammary cancer treatment in female dogs

457 | Feb 17 2023

This study found that the bioavailability of carboplatin increased when combined with ivermectin and cyclophosphamide in rats, but with a higher increase in the latter, suggesting a slight reduction in carboplatin's dose when combined with cyclophosphamide to avoid increased adverse effects. [Read the Full Post]

Antidepressant drugs use and epilepsy risk: A nationwide nested case-control study

183 | Feb 16 2023

A case-control study in Taiwan found a higher risk of epilepsy among patients exposed to antidepressants, particularly with longer-term use, and showed a higher risk for escitalopram, venlafaxine, mirtazapine, paroxetine, and fluoxetine, but not for sertraline, fluvoxamine, citalopram, duloxetine, milnacipran, and bupropion. [Read the Full Post]

Overview of Cochrane Systematic Reviews of rehabilitation interventions for persons with rheumatoid arthritis: a mapping synthesis

146 | Feb 13 2023

This paper provides an overview of Cochrane Systematic Reviews on the effectiveness of rehabilitation interventions for rheumatoid arthritis, including physical activity and exercises, psychosocial interventions, and pharmacological agents, with physical activity and exercises being effective for some outcomes and pharmacological agent celecoxib having similar pain relief effects with fewer adverse events compared to traditional NSAIDs, but inconclusive results for some interventions due to low quality of evidence. [Read the Full Post]

Efficacy of Kampo medicine Kakkonto as acute medication to treat tension-type headache among musculoskeletal pain patients using regular analgesics

170 | Feb 13 2023

Kakkonto showed efficacy as an acute medication for Tension-Type Headache with comorbidities, as it improved the pain score without any side effects in a small study of 10 patients with various painful comorbidities who had taken other analgesics. [Read the Full Post]

Melatonin activates mitochondrial unfolded protein response to preserve osteogenic potential of senescent BMSCs via upregulating PDI-6

296 | Feb 06 2023

PDI-6, a regulator of mitochondrial homeostasis, is a target for melatonin in the treatment of age-related osteoporosis due to its ability to enhance osteogenic differentiation in senescent BMSCs, which has decreased function, by rescuing mitochondrial function and being a downstream effector of the Wnt/β-catenin pathway. [Read the Full Post]

Insights into the antioxidative mechanisms of melatonin in ameliorating chromium-induced oxidative stress-mediated hepatic and renal tissue injuries in male Wistar rats

319 | Feb 06 2023

Melatonin has been shown to protect against chromium-induced oxidative damage in liver and kidney tissues by preserving organ weight, intracellular antioxidant enzymes, and reducing tissue chromium content, oxidative stress biomarkers, and pro-oxidant enzyme activities through its antioxidant and metal-chelating activity. [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]

Addressing adherence to guidelines on prevention of acute chemotherapy-induced nausea and vomiting in pediatric patients

318 | Feb 04 2023

Guideline adherence for prevention of chemotherapy-induced nausea and vomiting improved significantly, particularly in the high emetogenic chemotherapy group, with education, addition of anti-emetics to formulary, and implementation of a standardized guideline tool, but further improvement is needed in the moderately emetogenic chemotherapy group. [Read the Full Post]

Antiemetic use and chemotherapy induced nausea and vomiting related hospitalization costs after highly or moderately emetogenic chemotherapy

301 | Feb 04 2023

PrecisionQ's database analysis found lower CINV related hospitalization costs among patients receiving netupitant/fosnetupitant with palonosetron (NEPA) compared to aprepitant/fosaprepitant with ondansetron (APON) or aprepitant/fosaprepitant with palonosetron (APPA) during highly emetogenic chemotherapy or moderately emetogenic chemotherapy. [Read the Full Post]

SS18-SSX drives CREB activation in synovial sarcoma

126 | Jan 24 2023

Magdalene Cyra et al. showed that CREB was phosphorylated and activated in SySa, accompanied by downstream target expression. [Read the Full Post]

Notch signaling-induced cyclin d1 in diabetes ameliorating effects of the isolated polysaccharide from Rosa canina: In vitro and in vivo studies

365 | Nov 30 2022

Soraya Sajadimajd et al. thought that upregulation of Notch signaling-induced cyclin d1 could be proposed as the underlying diabetes-reducing effects of the isolated polysaccharide derivative. [Read the Full Post]

Management of adverse events related to first-generation tyrosine receptor kinase inhibitors in adults: a narrative review

244 | Nov 04 2022

Christine Martineau et al. thought that adequate management of AEs associated with TRKi in adults should be a prime focus. [Read the Full Post]

Discovery and functional characterization of the oncogenicity and targetability of a novel NOTCH1-ROS1 gene fusion in pediatric angiosarcoma

229 | Nov 04 2022

Payal Jain et al. found that oral entrectinib treatment effectively suppressed the growth of NOTCH-ROS1-driven tumors. [Read the Full Post]

ATRA works synergistically with the γ-secretase inhibitor crenigacestat to augment BCMA on multiple myeloma and the efficacy of BCMA-CAR T-cells

159 | Oct 10 2022

Estefanía García-Guerrero et al. found that ATRA treatment lead to enhanced BCMA expression on MM cells and consecutively, enhanced reactivity of BCMA-CAR T-cells. [Read the Full Post]

Prophylactic evaluation of verubecestat on disease- and symptom-modifying effects in 5XFAD mice

217 | Oct 09 2022

Adrian L Oblak et al. demonstrated the rigorous translational approaches of the MODEL-AD PTC for interrogating potential therapeutics and provided insight into the limitations of verubecestat as a prophylactic intervention for early-stage AD. [Read the Full Post]

BDNF and its signaling in cancer

363 | Oct 07 2022

Mohammad Malekan et al. found that the aberrant signaling of BDNF was implicated in various cancers. [Read the Full Post]

ABCB1 and ABCG2 Control Brain Accumulation and Intestinal Disposition of the Novel ROS1/TRK/ALK Inhibitor Repotrectinib, While OATP1A/1B, ABCG2, and CYP3A Limit Its Oral Availability

278 | Oct 07 2022

Wenlong Li et al. found that systemic exposure of repotrectinib was substantially limited by CYP3A activity. [Read the Full Post]

Down-regulated NEDD4L facilitates tumor progression through activating Notch signaling in lung adenocarcinoma

318 | Aug 25 2022

Liping Lin et al. demonstrated that down-regulated NEDD4L facilitated LUAD progression by activating Notch signaling, and NEDD4L might be a promising target to treat LUAD. [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]

An isogenic panel of App knock-in mouse models: Profiling β-secretase inhibition and endosomal abnormalities

124 | Jun 20 2022

Naoto Watamura et al. found that multiple factors, including elevated C-terminal fragment β (CTF-β) and humanization of Aβ might influence endosomal alterations in vivo. [Read the Full Post]

Systematic Evaluation for the Influences of the SOX17/Notch Receptor Family Members on Reversing Enzalutamide Resistance in Castration-Resistant Prostate Cancer Cells

401 | Jun 12 2022

Zhongbo Du et al. thought that the Notch1 and Notch4 inhibitors GSI-IX and RO4929097 were promising therapeutic agents for the treatment of CRPC. [Read the Full Post]

Synthesis, structural characterization, DFT calculations, molecular docking, and molecular dynamics simulations of a novel ferrocene derivative to unravel its potential antitumor activity

742 | Jun 12 2022

Mohamed M Hammoud et al. revealed the antitumor potential of ferrocene derivative (10) through targeting and inhibiting mitogen-activated protein (MAP) kinases interacting kinase (Mnk) 1.Communicated by Ramaswamy H. Sarma. [Read the Full Post]

Antithrombotic Therapy in Elderly Patients with Acute Coronary Syndromes

440 | Jun 11 2022

Clara Bonanad et al. it is imperative to deepen our knowledge regarding the management of these challenging patients through real-world data and specifically designed geriatric studies to help resolve the questions remaining in their disease management. [Read the Full Post]

The effect of danusertib, an Aurora kinase inhibitor, onto the cytotoxicity, cell cycle and apoptosis in pancreatic ductal adenocarcinoma cells

967 | Mar 11 2022

Ismail Ayberk Kirbiyik et al. thought that Aurora kinase inhibitor danusertib might be a potential alternative to the treatment of pancreatic cancers. [Read the Full Post]

Combined Inhibition of Polo-Like Kinase-1 and Wee1 as a New Therapeutic Strategy to Induce Apoptotic Cell Death in Neoplastic Mast Cells

1000 | Mar 10 2022

Manuela Mancini et al. showed that repurposing Plk1 or AKA ± Wee1 inhibitors in advanced clinical development for other indications was a therapeutic strategy worthy of being explored, in order to improve the outcome of patients with advanced SM. [Read the Full Post]

Radiotherapy alters expression of molecular targets in prostate cancer in a fractionation- and time-dependent manner

415 | Mar 09 2022

Iris Eke et al. found that understanding the molecular short- and long-term changes after irradiation could aid in optimizing the efficacy of multimodal radiation oncology in combination with post-irradiation molecularly-targeted drug treatment and improving the outcome of prostate cancer patients. [Read the Full Post]

P-Glycoprotein (ABCB1/MDR1) and BCRP (ABCG2) Limit Brain Accumulation and Cytochrome P450-3A (CYP3A) Restricts Oral Exposure of the RET Inhibitor Selpercatinib (RETEVMO)

222 | Feb 28 2022

Yaogeng Wang et al. thought that CYP3A-mediated metabolism could limit selpercatinib oral exposure and hence its tissue concentrations. [Read the Full Post]

Acyclovir Brain Disposition: Interactions with P-gp, Bcrp, Mrp2, and Oat3 at the Blood-Brain Barrier

333 | Feb 27 2022

Yuheng Shan et al. demonstrated that P-gp, Bcrp, Mrp2, and Oat3 inhibition increased the penetration of acyclovir across the BBB, supporting the hypothesis that these efflux pumps restrict the distribution of acyclovir in the brain. [Read the Full Post]

Paracrine production of IL-6 promotes a hypercoagulable state in pancreatic cancer

587 | Feb 09 2022

Silu Wang et al. found the key role of the Jagged/Notch/IL-6/STAT3 feedback loop in the development of a hypercoagulable state in pancreatic cance. [Read the Full Post]

γ-Secretase inhibitors for breast cancer and hepatocellular carcinoma: From mechanism to treatment

593 | Feb 09 2022

Hui Jia et al. thought that the γ-secretase complex was very important for activation of the Notch receptor and regulation of target-gene transcription. [Read the Full Post]

Rifampin and ritonavir increase oral availability and elacridar enhances overall exposure and brain accumulation of the NTRK inhibitor larotrectinib

344 | Jan 26 2022

Yaogeng Wang et al.found that elacridar enhanced both larotrectinib plasma and tissue exposure and especially relative brain penetration, which might be therapeutically relevant. [Read the Full Post]

PET imaging to assess the impact of P-glycoprotein on pulmonary drug delivery in rats

319 | Jan 24 2022

Irene Hernández-Lozano et al. found that P-gp could affect the pulmonary disposition of inhaled P-gp substrates. [Read the Full Post]

DR-5 and DLL-4 mAb Functionalized SLNs of Gamma-Secretase Inhibitors- An Approach for TNBC Treatment

517 | Jan 06 2022

Mamta Kumari et al. found that DLL4 mAb and GSIs were expected to act synergistically to block the Notch signal mediated BCSCs proliferation, differentiation, and metastasis. [Read the Full Post]

Detection of gene mutations and gene-gene fusions in circulating cell-free DNA of glioblastoma patients: an avenue for clinically relevant diagnostic analysis

723 | Dec 11 2021

Vikrant Palande et al. found that new avenues for precision medicine in GBM, using non-invasive liquid biopsy diagnostics to assess personalized patient profiles. Moreover, repeated detection of druggable targets over the course of the disease may provide real-time information on the evolving molecular landscape of the tumour. [Read the Full Post]

Detection of gene mutations and gene-gene fusions in circulating cell-free DNA of glioblastoma patients: an avenue for clinically relevant diagnostic analysis

597 | Dec 10 2021

Vikrant Palande et al. suggested that integrated analysis of cfDNA plasma concentration, gene mutations and gene-gene fusions could serve as a diagnostic modality for distinguishing GBM patients who might benefit from targeted therapy. [Read the Full Post]

BACE1 controls synaptic function through modulating release of synaptic vesicles

0 | Nov 16 2021

Brati Das et al. suggested that a therapy combining BACE1 inhibitors for reducing amyloid deposition and an mGluR1 PAM for counteracting BACE1-mediated synaptic deficits appeared to be an effective approach for treating AD patients. [Read the Full Post]

A phase 1b study of the Notch inhibitor crenigacestat (LY3039478) in combination with other anticancer target agents (taladegib, LY3023414, or abemaciclib) in patients with advanced or metastatic solid tumors

451 | Nov 16 2021

Analia Azaro et al. demonstrated that crenigacestat combined with different anticancer agents was poorly tolerated, leading to lowered dosing and disappointing clinical activity in patients with advanced or metastatic solid tumors. [Read the Full Post]

Spinal beta-amyloid1-42 acts as an endogenous analgesic peptide in CCI-induced neuropathic pain

279 | Nov 15 2021

Dong Cui et al. suggested that spinal Aβ1-42 acted as an endogenous analgesic peptide through regulating cytokines and Wnt pathways. [Read the Full Post]

Molecular Characteristics of Repotrectinib That Enable Potent Inhibition of TRK Fusion Proteins and Resistant Mutations

937 | Nov 14 2021

Brion W Murray et al. thought that repotrectinib was the most potent inhibitor of wild-type TRKA/B/C fusions and was more potent than selitrectinib against all tested resistance mutations. [Read the Full Post]

Translational Strategies for Repotrectinib in Neuroblastoma

758 | Nov 14 2021

Tara J O'Donohue et al. demonstrated that repotrectinib had antitumor activity in genotypically diverse neuroblastoma models. [Read the Full Post]

γ-secretase inhibitors, DAPT and RO4929097, promote the migration of Human Glioma Cells via Smad5-downregulated E-cadherin Expression

1527 | Oct 01 2021

Shun-Fu Chang et al. showed that γ-secretase activity inhibition by DAPT and RO4929097 could promote LN18 and LN229 glioma cell migration via downregulating E-cadherin mRNA and protein expressions, but not via affecting E-cadherin protein processing. [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]

Notch inhibitors induce diarrhea, hypercrinia and secretory cell metaplasia in the human colon

992 | Aug 30 2021

Michael Collins et al. confirmed the role of Notch signaling in intestinal homeostasis in humans. [Read the Full Post]

BACE1 controls synaptic function through modulating release of synaptic vesicles

547 | Jul 29 2021

Brati Das et al. suggested that a therapy combining BACE1 inhibitors for reducing amyloid deposition and an mGluR1 PAM for counteracting BACE1-mediated synaptic deficits appeared to be an effective approach for treating AD patients. [Read the Full Post]

Incidence, predictors, and outcomes of DAPT non-compliance in planned vs. ad hoc PCI in chronic coronary syndrome

1144 | Jul 21 2021

Jahanzeb Malik et al. provided an insight on additional predictors of non-compliance to DAPT, helping us to identify and address specific patient-related factors for disruption. [Read the Full Post]

Angiokinase inhibition of VEGFR-2, PDGFR and FGFR and cell growth inhibition in lung cancer: Design, synthesis, biological evaluation and molecular docking of novel azaheterocyclic coumarin derivatives

1612 | Jul 21 2021

Eman Y Ahmed et al. found that 4a was capable of arresting the cell cycle at pre-G1 phase and S phase and inducing apoptosis. [Read the Full Post]

Selective Secretase Targeting for Alzheimer's Disease Therapy

377 | May 05 2021

Alvaro Miranda et al. summarized structures and the activities of the latest compounds designed for AD treatment, with remarkable in vitro, in vivo, and clinical phase activities. [Read the Full Post]

Depletion of insulin-like growth factor 1 receptor increases radiosensitivity in colorectal cancer

760 | Mar 21 2021

Yi Li et al. supported the notion that the radiosensitivity of radiation-resistant colorectal cancer cells could be enhanced by directly targeting IGF1R expression or activity. [Read the Full Post]

The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice

442 | Mar 10 2021

Belén Vicente et al. thought that even in the presence of pharmacological inhibition of P-glycoprotein or cytochrome P450 3A, did not result in effective prophylaxis for S. mansoni infection in an experimental murine model. [Read the Full Post]

Optimization of dose and route of administration of the P-glycoprotein inhibitor, valspodar (PSC-833) and the P-glycoprotein and breast cancer resistance protein dual-inhibitor, elacridar (GF120918) as dual infusion in rats

435 | Mar 09 2021

Christopher Rowbottom rt al. demonstrated that doses greater than 0.9 mg/hr/kg valspodar and 8.9 mg/hr/kg elacridar were sufficient to inhibit P-gp- and BCRP-mediated efflux at the blood-brain barrier in rats without any tolerability issues. [Read the Full Post]

More Insights on the Use of γ-Secretase Inhibitors in Cancer Treatment

842 | Feb 21 2021

Pilar López-Nieva et al. suggested that selective targeting γ-secretase might offer an improved efficacy and toxicity profile over the effects caused by broad-spectrum GSIs. [Read the Full Post]

Active notch protects MAPK activated melanoma cell lines from MEK inhibitor cobimetinib

810 | Feb 19 2021

Letizia Porcelli et al. unveiled a coordinate action of MAPK and Notch signaling in promoting proliferation of BRAFV600E MM and GNAQQ209L UM cells. [Read the Full Post]

Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Adults

582 | Feb 01 2021

D Gwyn Bebb et al. recommend considering a TRK inhibitor in all patients with TRK fusion cancer with no other effective treatment options. [Read the Full Post]

Relation of Metal-Binding Property and Selective Toxicity of 8-Hydroxyquinoline Derived Mannich Bases Targeting Multidrug Resistant Cancer Cells

533 | Jan 31 2021

Veronika F S Pape et al. showed that the MDR-selective anticancer activity of the studied 8-hydroxyquinoline derived Mannich bases was associated with the iron deprivation of MDR cells and the preferential formation of redox-active copper(II) complexes, which underwent intracellular redox-cycling to induce oxidative stress. [Read the Full Post]

Nanog maintains stemness of Lkb1-deficient lung adenocarcinoma and prevents gastric differentiation

941 | Jan 15 2021

Xinyuan Tong et al. uncovered a previously unappreciated plasticity of LKB1-deficient tumors and identified the Nanog-Notch axis in regulating gastric differentiation, which hold important therapeutic implication for the treatment of mucinous lung cancer. [Read the Full Post]

Evaluation of NTRK immunohistochemistry as a screening method for NTRK gene fusion detection in non-small cell lung cancer

868 | Dec 23 2020

Hedvig Elfving et al. found that the presence of NTRK fusion genes in non-small cell lung cancer was exceedingly rare. The use of the immunohistochemical NTRK assay would result in a small number of false positive cases. [Read the Full Post]

Clinicopathologic, Genomic, and Protein Expression Characterization of 356 ROS1 Fusion Driven Solid Tumors Cases

760 | Dec 22 2020

Richard S P Huang et al. characterized a large cohort of ROS1 fusionpos NSCLC and non-NSCLC solid tumors and discovered 10 novel ROS1 fusions. [Read the Full Post]

Phase 1 study to evaluate Crenigacestat (LY3039478) in combination with dexamethasone in patients with T-cell acute lymphoblastic leukemia and lymphoma

730 | Nov 28 2020

Gautam Borthakur et al. found that crenigacestat demonstrated limited clinical activity at the recommended dose in adult patients with relapsed/refractory T-ALL/T-LBL. [Read the Full Post]

Further analyses of the safety of verubecestat in the phase 3 EPOCH trial of mild-to-moderate Alzheimer's disease

362 | Nov 27 2020

Michael F Egan et al. thought that verubecestat was associated with increased risk for several types of adverse events. [Read the Full Post]

Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells

0 | Nov 24 2020

Diana Cervantes-Madrid et al. showed that repotrectinib was capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibited strong antitumor effects in a xenograft model of neuroblastoma. [Read the Full Post]

Cases of ROS1-rearranged lung cancer: when to use crizotinib, entrectinib, lorlatinib, and beyond?

788 | Nov 23 2020

Kartik Sehgal et al. described cases of advanced ROS1-rearranged lung cancer receiving crizotinib, entrectinib, and/or lorlatinib in first and later line treatment settings to dissect the current state of evidence supporting management decisions for these patients. [Read the Full Post]

Targeting the Notch and TGF-β signaling pathways to prevent retinal fibrosis in vitro and in vivo

1051 | Sep 27 2020

Jiawen Fan et al. foung that inhibiting Notch signaling might be an effective way to prevent retinal fibrosis. [Read the Full Post]

GSK3β-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration

1476 | Aug 19 2020

Youpei Wang et al. provided a new regulatory mechanism by which GSK3β negatively regulated human skin fibroblast cell migration. [Read the Full Post]

Tumour-associated neutrophils orchestrate intratumoural IL-8-driven immune evasion through Jagged2 activation in ovarian cancer

939 | Aug 12 2020

Moran Yang et al. found that JAG2+TANs were closely linked to IL-8-driven immune evasion microenvironment and might serve as a promising therapeutic target for the reinvigoration of anti-tumour immunity. [Read the Full Post]

Quantification and Pharmacokinetic Property of Verubecestat an BACE1 Inhibitor in Rat Plasma

446 | Jun 29 2020

Qiong Wang et al. designed an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) approach to measure the rat plasma levels of verubecestat with diazepam as the internal standard. [Read the Full Post]

Notch Signaling Pathway Is a Potential Therapeutic Target for Extracranial Vascular Malformations

0 | Jun 22 2020

Reema B Davis et al. provided further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations. [Read the Full Post]

Overexpression of Fibroblast Growth factor-21 (FGF-21) Protects Mesenchymal Stem Cells Against Caspase-Dependent Apoptosis Induced by Oxidative Stress and Inflammation

1541 | Jun 22 2020

Gabriel R Linares et al. provided compelling evidence that FGF-21 played a crucial role in protecting MSCs from apoptosis induced by oxidative stress and inflammation, and merited further investigation as a strategy for enhancing the therapeutic efficacy of stem cell-based therapies. [Read the Full Post]

A Systematic Review of the Studies That Evaluate the Performance of the DAPT Score

1059 | Jun 21 2020

Chun Shing Kwok et al. showd that the DAPT score had modest predictive value for ischemic and bleeding outcomes.A prospective randomized controlled trial was needed to evaluate the clinical benefits of utilising the DAPT score in guiding continued DAPT therapy beyond 1 year. [Read the Full Post]

DAPT Score and the Impact of Ticagrelor Monotherapy During the Second Year After PCI

1165 | Jun 18 2020

Ply Chichareon et al. found that the DAPT score can stratify ischemic but not bleeding risk in a contemporary PCI population during the second year. [Read the Full Post]

Notch signaling pathway is a potential therapeutic target for extracranial vascular malformations

0 | Apr 11 2020

Davis RB et al. provided further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations. [Read the Full Post]

Impact of high on-treatment platelet reactivity after angioplasty in patients with peripheral arterial disease

788 | Apr 10 2020

Busch L et al. suggested that MALE might be associated with dual HTPR. [Read the Full Post]

Crenigacestat, a selective NOTCH1 inhibitor, reduces intrahepatic cholangiocarcinoma progression by blocking VEGFA/DLL4/MMP13 axis

0 | Apr 06 2020

Mancarella S et al. provided new knowledge on Notch signaling in iCCA, and support the inhibition of the Notch cascade as a promising strategy for the treatment of this disease. [Read the Full Post]

BACE1 Inhibitor MK-8931 Alters Formation but Not Stability of Dendritic Spines

0 | Apr 05 2020

Blume T et al. suggested that carefully dosed inhibitors might be therapeutically effective without affecting the structural integrity of excitatory synapses if given at an early disease stage. [Read the Full Post]

NTRK fusion-positive cancers and TRK inhibitor therapy

994 | Mar 23 2020

Cocco E et al. discussed the biology of NTRK fusions, strategies to target these drivers in the treatment-naive and acquired-resistance disease settings, and the unique safety profile of TRK inhibitors. [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]

Randomized Trial of Verubecestat for Prodromal Alzheimer's Disease

530 | Feb 23 2020

Michael F Egan et al. indicated that verubecestat did not improve clinical ratings of dementia among patients with prodromal Alzheimer's disease, and some measures suggested that cognition and daily function were worse among patients who received verubecestat than among those who received placebo. [Read the Full Post]

Crenigacestat, a Selective NOTCH1 Inhibitor, Reduces Intrahepatic Cholangiocarcinoma Progression by Blocking VEGFA/DLL4/MMP13 Axis

1464 | Feb 23 2020

Serena Mancarella et al. developed and validated a new iCCA PDX model to test in vivo the activity of LY3039478, demonstrating its inhibitory role in Notch-dependent angiogenesis. Thus, the present data provide new knowledge on Notch signaling in iCCA, and support the inhibition of the Notch cascade as a promising strategy for the treatment of this disease. [Read the Full Post]

BACE1 Inhibitor MK-8931 Alters Formation but Not Stability of Dendritic Spines

554 | Feb 20 2020

Tanja Blume et al. suggested that carefully dosed inhibitors might be therapeutically effective without affecting the structural integrity of excitatory synapses if given at an early disease stage. [Read the Full Post]

Adavosertib (AZD1775) in Combination With Gemcitabine and Radiation for Patients With Locally Advanced Pancreatic Cancer

490 | Feb 20 2020

Kyle C Cuneo et al. indicated that AZD1775 in combination with gemcitabine and radiation therapy was well tolerated at a dose that produced target engagement in a surrogate tissue. The overall survival is substantially higher than prior results combining gemcitabine with radiation therapy and warrants additional investigation. [Read the Full Post]

Anti-myeloma effect of pharmacological inhibition of Notch/gamma-secretase with RO4929097 is mediated by modulation of tumor microenvironment

819 | Dec 02 2019

Pisklakova A et al. indicated that targeting Notch may be considered as a new strategy to be tested for MM therapy. [Read the Full Post]

Exogenous mesenchymal stem cells affect the function of endogenous lung stem cells (club cells) in phosgene-induced lung injury

0 | Oct 21 2019

Ye K et al. showed that MSCs reduced the secretion of club cells. And MSCs enhanced the proliferation of club cells partly via activating the Notch signaling pathway, which promoted lung injury repair. [Read the Full Post]

The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer's disease patients

950 | Aug 27 2019

Kennedy ME indicated the human data were fit to an amyloid pathway model that provided insight into the Aβ pools affected by BACE1 inhibition and guided the choice of doses for subsequent clinical trials. [Read the Full Post]

Notch signaling pathway is a potential therapeutic target for extracranial vascular malformations

1913 | Aug 18 2019

Davis RB et al. showed that two gamma secretase inhibitors (GSIs), DAPT (GSI-IX) and RO4929097, cause dose-dependent inhibition of Notch target gene expression (Hey1) and rate of migration of monolayer cultures of lymphatic endothelial cells (hLECs) and blood endothelial cells (HUVEC). GSIs also inhibit HUVEC network formation. hLECs are more sensitive to GSIs compared to HUVEC. GSIs have been found to be safe in clinical trials in patients with Alzheimer's disease or cancer. Our results provide further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations. [Read the Full Post]

Clinical relevance of ticagrelor monotherapy following 1-month dual antiplatelet therapy after bifurcation percutaneous coronary intervention: Insight from GLOBAL LEADERS trial

815 | Aug 16 2019

Kogame N et al. found that after PCI for bifurcation lesions using 1-month of DAPT followed by ticagrelor monotherapy for 23 months did not demonstrate explicit benefit regarding all-cause death or new Q-wave MI as in the overall trial. [Read the Full Post]

Use of Antiplatelet Therapy/DAPT for Post-PCI Patients Undergoing Noncardiac Surgery

870 | Aug 14 2019

Banerjee S et al. present3 commonly encountered clinical scenarios that lead into an evidence-based discussion of practical strategies for managing perioperative antiplatelet therapy in patients following percutaneous coronary intervention. [Read the Full Post]

Exogenous mesenchymal stem cells affect the function of endogenous lung stem cells (club cells) in phosgene-induced lung injury

847 | Jul 05 2019

Ye K et al. showed that MSCs reduced the secretion of club cells. And MSCs enhanced the proliferation of club cells partly via activating the Notch signaling pathway, which promoted lung injury repair. [Read the Full Post]

Chronic Verubecestat Treatment Suppresses Amyloid Accumulation in Advanced Aged Tg2576-AβPPswe Mice Without Inducing Microhemorrhage

944 | Jul 02 2019

Villarreal S et al. showed the absence of elevated ARIA events in verubecestat-treated mice was associated with a significant reduction in the level of accumulated CNS amyloid pathology and brain Aβ peptides; effects consistent with the desired therapeutic mechanism of verubecestat in AD patients. These data will be compared with longitudinal MRI profiles from ongoing clinical trials. [Read the Full Post]

Efficacy of Ramelteon for delirium after lung cancer surgery

831 | Jun 20 2019

Miyata R et al. showed that Ramelteon is likely to reduce the incidence and intensity of delirium after surgery for lung cancer in elderly patients. [Read the Full Post]

Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β-endorphin and methionine-enkephalin

0 | Mar 16 2019

Hiramoto K et al. suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma. [Read the Full Post]

Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9

779 | Feb 12 2019

Guo D et al. found that pancreatic differentiation of ABCC8-deficient cells recapitulated the CHI disease phenotype in vitro, which represents an attractive model to further elucidate the function of SUR1 and to develop and screen for novel therapeutic drugs. [Read the Full Post]

Inhibition of the NOTCH pathway using γ-secretase inhibitor RO4929097 has limited antitumor activity in established glial tumors

2781 | Feb 05 2019

Dantas-Barbosa C et al. indicated that RO4929097-mediated effects were independent of NOTCH1 mutation status or expression levels, but associated with low IL-6 levels. In established glial tumor models, NOTCH inhibition had limited effects as a single agent, but enhanced efficacy when combined with DNA-interfering agents. These preclinical data need to be considered for further clinical development of NOTCH inhibitors in glial tumors. [Read the Full Post]

Inhibition of γ-secretase activity synergistically enhances tumour necrosis factor-related apoptosis-inducing ligand induced apoptosis in T-cell acute lymphoblastic leukemia cells via upregulation of death receptor 5

517 | Jan 28 2019

Greene LM et al. found that DAPT/TRAIL apoptotic synergy was dependent on the extrinsic apoptotic pathway and was associated with a decrease in BH3 interacting-domain death agonist and x-linked inhibitor of apoptosis. In conclusion, γ-secretase inhibition represents a potential therapeutic strategy to overcome TRAIL resistance for the treatment of T-ALL. [Read the Full Post]

Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β-endorphin and methionine-enkephalin

1257 | Jan 25 2019

Hiramoto K et al. suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma. [Read the Full Post]

Boosting Endogenous Resistance of Brain to Ischemia

0 | Jan 20 2019

Sun F et al. indicated the therapeutic activation of α7 nAChRs after cerebral ischemia may serve as an important physiological responsibility of these ubiquitous receptors and holds a significant translational potential. [Read the Full Post]

The pharmacokinetics and metabolism of lumiracoxib in chimeric humanized and murinized FRG mice

971 | Jan 06 2019

Dickie AP et al. showed taht comparison of the metabolic profiles obtained from the present study with previously published data from C57bl/6J mice and humans, revealed a greater though not complete match between chimeric humanized mice and humans, such that the liver-humanized FRG model may represent a useful approach to assessing the biotransformation of such compounds in humans. [Read the Full Post]

Tracking gastrointestinal transit of solids in aged rats as pharmacological models of chronic dysmotility

0 | Dec 28 2018

Dalziel JE et al. demonstrated that loperamide slowed overall transit in aged rats, while prucalopride increased stomach emptying and accelerates colonic transit. [Read the Full Post]

Procaine Attenuates Pain Behaviors of Neuropathic Pain Model Rats Possibly via Inhibiting JAK2/STAT3

0 | Dec 28 2018

Li D et al. indicated that procaine is capable of attenuating NPP, suggesting procaine is a potential therapeutic strategy for treating NPP. Its role may be associated with the inhibition on JAK2/STAT3 signaling. [Read the Full Post]

FBW7 mutations mediate resistance of colorectal cancer to targeted therapies by blocking Mcl-1 degradation

0 | Dec 19 2018

Tong J et al. demonstrated FBW7 mutational status as a key genetic determinant of CRC response to targeted therapies, and Mcl-1 as an attractive therapeutic target. [Read the Full Post]

Spinal Glutamate Transporters Are Involved in the Development of Electroacupuncture Tolerance

1366 | Dec 16 2018

Cui L et al. indicated the participation of the spinal GTs in EAT. [Read the Full Post]

HDAC10 promotes lung cancer proliferation via AKT phosphorylation

958 | Dec 12 2018

Yang Y et al. demonstrated that HDAC10 localizes and functions in the cytoplasm of lung cancer cells, thereby underscoring its potential role in the diagnosis and treatment of lung cancer. [Read the Full Post]

5-HT4 receptors facilitate cholinergic neurotransmission throughout the murine gastrointestinal tract

1172 | Dec 11 2018

Pauwelyn V et al. showed that in the murine gastrointestinal tract, activation of 5-HT4 receptors with prucalopride enhances cholinergic contractions, illustrating facilitation of myenteric cholinergic neurotransmission. The degree of enhancement with prucalopride is of similar magnitude as previously reported in other species, but the effective concentrations are lower than those needed in the gastrointestinal tract of other species. [Read the Full Post]

Levo-Tetrahydroberberrubine Produces Anxiolytic-Like Effects in Mice through the 5-HT1A Receptor

1074 | Nov 30 2018

Mi G et al. suggested that l-THBr may produce potent anxiolytic-like effects mainly through serotonin receptors. [Read the Full Post]

Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis of the multidrug transporter P-glycoprotein

0 | Nov 20 2018

Chufan EE et al. revealed that screening chemical compounds for their ability to inhibit the basal ATP hydrolysis can be a reliable tool to identify modulators with high affinity for P-gp. [Read the Full Post]

An RNA interference screen identifies new avenues for nephroprotection

1069 | Oct 05 2018

Zynda ER et al. shed new light on the mechanisms of stress response in mammalian cells, and open new avenues to reduce the morbidity and mortality associated with renal injury. [Read the Full Post]

Experimental observation of human bone marrow mesenchymal stem cell transplantation into rabbit intervertebral discs

1373 | Sep 30 2018

Tao H et al. indicated that in the sections of specimens removed at 1, 2, 4, 6 and 8 weeks post-transplantation, no GFP-positive cells were observed in the control groups, whereas GFP-positive cells were apparent in the nucleus pulposus at all periods in the GFP-labeled human BMSCs group, and the cell density at 6 and 8 weeks was significantly less than that at 1, 2 and 4 weeks post-transplantation (P<0.001). [Read the Full Post]

Cyclic cis-Locked Phospho-Dipeptides Reduce Entry of AβPP into Amyloidogenic Processing Pathway

2331 | Sep 24 2018

Fisher CL et al. suggested a model in which pCDP-diBzl and pCDP-diPOM act at a common point to inhibit entry of AβPP into the amyloidogenic AβPP processing pathway but through different targets, and provide important insights for the development of novel AD therapeutics. [Read the Full Post]

Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1

1125 | Sep 19 2018

Zhou TJ et al. suggested that mitochondrial COX-2 is a potential theranostic target for the CSCs in NPC. Inhibition of mitochondrial COX-2 could be an attractive therapeutic option for the effective clinical treatment of therapy-resistant NPC. [Read the Full Post]

A regulatory circuit of miR-125b/miR-20b and Wnt signalling controls glioblastoma phenotypes through FZD6-modulated pathways

1316 | Sep 19 2018

Huang T et al. confirmed by targeting differentially enriched pathways in PN versus MES GBM that results in inhibition of distinct GBM subtypes. Correlative expressions of the components of this circuit are prognostic relevant for clinical GBM. Our findings provide insights for understanding GBM pathogenesis and for improving treatment of GBM. [Read the Full Post]

The Effects of Ultraviolet Eye Irradiation on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice

1562 | Sep 15 2018

Hiramoto K et al. suggested that UV eye irradiation plays an important role in DSS-induced ulcerative colitis. [Read the Full Post]

Boosting Endogenous Resistance of Brain to Ischemia

1305 | Sep 14 2018

Sun F et al. found that the therapeutic activation of α7 nAChRs after cerebral ischemia may serve as an important physiological responsibility of these ubiquitous receptors and holds a significant translational potential. [Read the Full Post]

Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma

1757 | Sep 13 2018

Fan TF et al. found that inhibiting autophagy could enhance DHM-induced apoptosis in head and neck squamous cell carcinoma. [Read the Full Post]

Identification of ACTG2 functions as a promoter gene in hepatocellular carcinoma cells migration and tumor metastasis

1475 | Sep 11 2018

Wu Y et al. revealed a critical role of ACTG2 in HCC tumor metastasis, and renders it a novel target for the treatment of HCC. [Read the Full Post]

Fascin Is Critical for the Maintenance of Breast Cancer Stem Cell Pool Predominantly via the Activation of the Notch Self-Renewal Pathway

1384 | Sep 11 2018

Barnawi R et al. demonstrated fascin as a critical regulator of breast CSC pool at least partially via activation of the Notch self-renewal signaling pathway and modification of the expression embryonic transcriptional factors. Targeting fascin may halt CSCs and thus presents a novel therapeutic approach for effective treatment of breast cancer. [Read the Full Post]

Disruption of clathrin-dependent trafficking results in the failure of grass carp reovirus cellular entry

1621 | Sep 08 2018

Wang H et al. suggested that GCRV might enter CIK cells via clathrin-mediated endocytosis in a pH-dependent manner. Additionally, dynamin is critical for efficient viral entry. [Read the Full Post]

PCSK9-deficiency does not alter blood pressure and sodium balance in mouse models of hypertension

1112 | Sep 06 2018

Berger JM et al. found that PCSK9-deficiency did not alter both basal blood pressure and its increase in salt-insensitive (l-NAME) and salt-sensitive (Ang-II and DOCA-salt) hypertension models. [Read the Full Post]

Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus

0 | Sep 06 2018

Cui R et al. provide a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. [Read the Full Post]

The Nonmetabolized β-Blocker Nadolol Is a Substrate of OCT1, OCT2, MATE1, MATE2-K, and P-Glycoprotein, but Not of OATP1B1 and OATP1B3

2905 | Sep 05 2018

Misaka S et al. indicated that these data will aid future in vivo studies on potential transporter-mediated drug-drug or drug-food interactions with involvement of nadolol. [Read the Full Post]

Structure-dependent complexation of Fe3+ by anthracyclines. 2. The roles of methoxy and daunosamine functionalities

1026 | Aug 18 2018

Nawara K et al. illustrated the important role of methoxy and daunosamine moieties in anthracycline-iron(III) complex formation and stability. [Read the Full Post]

CRISPR/Cas-Mediated Knockin in Human Pluripotent Stem Cells

1580 | Aug 17 2018

The transfection procedures described could also be used for additional applications, such as overexpression or lineage tracing studies. [Read the Full Post]

BMS-708163 and Nilotinib restore synaptic dysfunction in human embryonic stem cell-derived Alzheimer's disease models

1675 | Aug 07 2018

Nishioka H et al. suggested that the AD models we developed are promising materials for the discovery of AD drugs that target the expression of pre-synaptic proteins and synaptic function. [Read the Full Post]

Cellular Prion Protein Mediates Pancreatic Cancer Cell Survival and Invasion through Association with and Enhanced Signaling of Notch1

1518 | Jul 29 2018

Wang Y et al. unraveled a novel molecular pathway driven by interactions between PrP and Notch1 in the progression of PDAC, supporting a critical tumor-promoting role of Notch1 in PrP-expressing PDAC tumors. [Read the Full Post]

Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation

1657 | Jul 27 2018

Figueiredo M et al. offered novel evidence on the role of Notch signalling in T/PT common primordium development, in an Hh-dependent manner. [Read the Full Post]

Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis

1548 | Jul 27 2018

Hasebe T et al. provided evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development. Stem Cells 2017;35:1028-1039. [Read the Full Post]

Aberrant Notch Signaling in the Bone Marrow Microenvironment of Acute Lymphoid Leukemia Suppresses Osteoblast-Mediated Support of Hematopoietic Niche Function

1614 | Jul 25 2018

Wang W et al. suggested that therapeutically targeting the leukemia-infiltrated hematopoietic niche may restore HSPC homeostasis and improve the outcome of ALL patients. [Read the Full Post]

Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis of the multidrug transporter P-glycoprotein

1379 | Jul 06 2018

Chufan EE et al. reveal that screening chemical compounds for their ability to inhibit the basal ATP hydrolysis can be a reliable tool to identify modulators with high affinity for P-gp. [Read the Full Post]

Inhibition of eEF-2 kinase sensitizes human nasopharyngeal carcinoma cells to lapatinib-induced apoptosis through the Src and Erk pathways

850 | May 30 2018

Liu L et al. suggested that targeting eEF-2 kinase may improve the efficacy of therapeutic interventions such as lapatinib in NPC cells. [Read the Full Post]

Gp130-mediated STAT3 activation by S-propargyl-cysteine, an endogenous hydrogen sulfide initiator, prevents doxorubicin-induced cardiotoxicity

1432 | May 11 2018

Wu J et al. offered a novel molecular basis and therapeutic strategy of H2S donor for the treatment of heart failure. [Read the Full Post]

A Platelet/CMC coupled with offline UPLC-QTOF-MS/MS for screening antiplatelet activity components from aqueous extract of Danshen

1326 | Apr 30 2018

Chen Y et al. suggested their retention time was closely related to the antiplatelet aggregation activities. This study provides a rapid, effective and novel method for screening the potential antiplatelet activity components from Chinese herb medicines. [Read the Full Post]

Lumiracoxib metabolism in male C57bl/6J mice: characterisation of novel in vivo metabolites

1393 | Apr 25 2018

P Dickie A et al. found that while there was significant overlap with reported human metabolites, a number of unique mouse metabolites were detected, particularly taurine conjugates of lumiracoxib and its oxidative metabolites. [Read the Full Post]

Mechanism for neurotropic action of vorinostat, a pan histone deacetylase inhibitor.

1096 | Apr 24 2018

Shukla S et al. suggested that vorinostat exerts a positive effect on the neuritogenesis via activation of MEK1/2 & PI3K pathways involving an upstream kinase, TrkA. Bioactive small molecules with neurotrophic and neuritogenic actions, like vorinostat identified in the present study, hold great promise as therapeutic agents for treatment of neurodegenerative diseases and neuronal injuries by virtue of their ability to stimulate neuritic outgrowth. [Read the Full Post]

Evaluation of cardioprotective effect of aqueous extract of Garcinia indica Linn. fruit rinds on isoprenaline-induced myocardial injury in Wistar albino rats

1545 | Apr 18 2018

Patel KJ et al. found that the aqueous extract of G. indica was not found to be cardioprotective against myocardial injury. [Read the Full Post]

Relative cytotoxic potencies and cell death mechanisms of α1 -adrenoceptor antagonists in prostate cancer cell lines

0 | Mar 17 2018

Forbes A et al. demonstrated cytotoxic actions on both castration-resistant PC-3 and androgen-sensitive LNCap prostate cancer cells. [Read the Full Post]

IgG subclasses determine pathways of anaphylaxis in mice

0 | Mar 09 2018

Beutier H et al. proposed that the differential expression of inhibitory FcγRIIB on myeloid cells and its differential binding of IgG subclasses controls the contributions of mast cells, basophils, neutrophils, and macrophages to IgG subclass-dependent anaphylaxis. [Read the Full Post]

Epigenetic Regulation of Interleukin 6 by Histone Acetylation in Macrophages and Its Role in Paraquat-Induced Pulmonary Fibrosis

3562 | Feb 06 2018

Hu L et al. indicated IL-6 functioning through EMT in PQ-induced pulmonary fibrosis was regulated dynamically by HDAC and HAT both in vitro and in vivo via epigenetically regulating chromatin accessibility. [Read the Full Post]

Prospective identification of resistance mechanisms to HSP90 inhibition in KRAS mutant cancer cells

1541 | Jan 20 2018

Rouhi A et al. identified potential mechanisms of acquired resistance to small molecules targeting HSP90 that may warrant proactive screening for additional HSP90 inhibitors or rational combination therapies. [Read the Full Post]

Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue

1861 | Dec 13 2017

Liu Z et al. revealed a novel function of melatonin on adipocyte pyroptosis, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory response. [Read the Full Post]

The HDAC Inhibitor LAQ824 Enhances Epigenetic Reprogramming and In Vitro Development of Porcine SCNT Embryos.

1634 | Dec 13 2017

Optimum exposure (100 nM for 24 h) to LAQ824 post-activation improved the in vitro development of porcine SCNT embryos by enhancing levels of H3K9 and H4K12, reducing 5-mC, and regulating gene expression. [Read the Full Post]

Differential expression of cyclooxygenase-2 in metastatic melanoma affects progression free survival

1748 | Nov 13 2017

Panza E et al. suggested that COX-2 expression may become an useful diagnostic tool in defining melanoma malignancy as well as argue for a possible therapeutic use of NSAID as add on therapy in selected cases. [Read the Full Post]

COX-2 expression positively correlates with PD-L1 expression in human melanoma cells

1732 | Nov 13 2017

Botti G et al. showed that COX-2 expression correlates with and modulates PD-L1 expression in melanoma cells. These findings have clinical relevance since they provide a rationale to implement novel clinical trials to test COX-2 inhibition as a potential treatment to prevent melanoma progression and immune evasion as well as to enhance the anti-tumor activity of PD-1/PD-L1 based immunotherapy for the treatment of melanoma patients with or without BRAF/NRAS mutations. [Read the Full Post]

Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment

2461 | Oct 24 2017

Katsushima K et al. showed that highlight the importance of the Notch-lncRNA axis in regulating self-renewal of glioma cells and provide a strong rationale for targeting TUG1 as a specific and potent therapeutic approach to eliminate the GSC population. [Read the Full Post]

Tetrandrine has anti-adipogenic effect on 3T3-L1 preadipocytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3

1277 | Oct 07 2017

Jang BC et al. show that tetrandrine has strong anti-adipogenic effect on 3T3-L1 preadipocytes and the effect is largely attributable to the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. [Read the Full Post]

Harmine Induces Adipocyte Thermogenesis through RAC1-MEK-ERK-CHD4 Axis

1548 | Sep 22 2017

Nie T et al. reveal a new application of harmine in combating obesity via this off-target effect in adipocytes. [Read the Full Post]

Procaine Attenuates Pain Behaviors of Neuropathic Pain Model Rats Possibly via Inhibiting JAK2/STAT3

2690 | Sep 21 2017

Li D et al. indicated that procaine is capable of attenuating NPP, suggesting procaine is a potential therapeutic strategy for treating NPP. Its role may be associated with the inhibition on JAK2/STAT3 signaling. [Read the Full Post]

P-glycoprotein confers acquired resistance to 17-DMAG in lung cancers with an ALK rearrangement

1186 | Sep 20 2017

Kim HJ et al. observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR and H460/PR cells generated to over-express P-gp by long-term exposure to paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the inhibition of P-gp. [Read the Full Post]

Paeoniflorin protects diabetic mice against myocardial ischemic injury via the transient receptor potential vanilloid 1/calcitonin gene-related peptide pathway

0 | Sep 16 2017

Han F et al. demonstrated that PF protects diabetic mice against MI at least partially via the TRPV1/CaMK/CREB/CGRP signaling pathway. [Read the Full Post]

Overexpression of cannabinoid receptor 1 promotes renal cell carcinoma progression

1323 | Sep 13 2017

Wang J et al. suggested that CB1 might be a potential target for RCC clinical therapy. [Read the Full Post]

miR-203 inhibits arecoline-induced epithelial-mesenchymal transition by regulating secreted frizzled-related protein 4 and transmembrane-4 L six family member 1 in oral submucous fibrosis

1432 | Sep 12 2017

Zheng L et al. provideD evidence to illustrate that miR-203 plays a role in the pathogenesis of OSF, which may be a target for OSF management. [Read the Full Post]

Intrathecal Intermittent Orexin-A Causes Sympathetic Long-Term Facilitation and Sensitizes the Peripheral Chemoreceptor Response to Hypoxia in Rats

1748 | Sep 12 2017

Kim SJ et al. revealed that the activation of spinal orexin receptors is critical to enhance peripheral chemoreceptor responses to hypoxia after AIH. [Read the Full Post]

Tracking gastrointestinal transit of solids in aged rats as pharmacological models of chronic dysmotility

2791 | Sep 11 2017

Dalziel JE et al. demonstrated that loperamide slowed overall transit in aged rats, while prucalopride increased stomach emptying and accelerates colonic transit. [Read the Full Post]

Riluzole partially rescues age-associated, but not LPS-induced, loss of glutamate transporters and spatial memory

2156 | Sep 11 2017

Brothers HM et al. showed that highlight the therapeutic potential of reducing glutamatergic function upon memory impairment in neurodegenerative diseases associated with aging. [Read the Full Post]

Essential role of Notch4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer

2425 | Jul 25 2017

Bui QT et al. concluded Notch4 could be a potential target to prevent metastasis in TAM-resistant breast cancer. [Read the Full Post]

Endosulfan inhibits proliferation through the Notch signaling pathway in human umbilical vein endothelial cells

2368 | Jul 25 2017

Wei J et al. demonstrated that endosulfan inhibited proliferation through the Notch signaling pathway as a result of oxidative stress. In addition, endosulfan can damage the cytoskeleton and block mitosis, which may add another layer of toxic effects on endothelial cells. [Read the Full Post]

Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents

0 | Jun 24 2017

Zhu J et al. showed that modifications beyond just increasing the lipophilicity of this class of Pgp inhibitors are beneficial to the activity. [Read the Full Post]

An RNA interference screen identifies new avenues for nephroprotection

0 | Jun 05 2017

Zynda ER et al. found new light on the mechanisms of stress response in mammalian cells, and open new avenues to reduce the morbidity and mortality associated with renal injury. [Read the Full Post]

The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid

0 | Jun 04 2017

Hiramoto K et al. suggested that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. [Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

0 | Jun 01 2017

Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]

"RNA polymerase III component Rpc9 regulates hematopoietic stem and progenitor cell maintenance in zebrafish. "

0 | Apr 17 2017

Wei Y et al illustrated that Rpc9, a component of Pol III, plays an important tissue-specific role in HSPC maintenance during zebrafish embryogenesis and might be conserved across vertebrates, including mammals. [Read the Full Post]

Resveratrol protects CA1 neurons against focal cerebral ischemic reperfusion-induced damage via the ERK-CREB signaling pathway in rats

0 | Apr 10 2017

Li Z et al found that the NMDA receptor-mediated ERK-CREB signaling pathway might participates in Res-induced neuroprotection in rats with focal cerebral ischemia. [Read the Full Post]

Targeting the Neurokinin-1 Receptor Compromises Canonical Wnt Signaling in Hepatoblastoma

0 | Mar 30 2017

Ilmer M et al revealed important insight into the molecular mechanisms of the SP/NK1R complex as a critical component in a model of pediatric liver cancer and may support the development of novel therapeutic interventions for HB and other Wnt-activated cancers. [Read the Full Post]

An RNA interference screen identifies new avenues for nephroprotection

0 | Mar 29 2017

Zynda ER et al shed new light on the mechanisms of stress response in mammalian cells, and open new avenues to reduce the morbidity and mortality associated with renal injury. [Read the Full Post]

The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid

0 | Mar 28 2017

Hiramoto K et al suggested that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. [Read the Full Post]

FBW7 mutations mediate resistance of colorectal cancer to targeted therapies by blocking Mcl-1 degradation

3143 | Mar 21 2017

Tong J et al. demonstrate FBW7 mutational status as a key genetic determinant of CRC response to targeted therapies, and Mcl-1 as an attractive therapeutic target. [Read the Full Post]

Endothelial Cell Apoptosis Induces TGF-b Signaling-Dependent Host Endothelial–Mesenchymal Transition to Promote Transplant Arteriosclerosis

3222 | Mar 05 2017

Li J et al. suggested that allograft EC apoptosis induced recipient endothelial-mesenchymal (smooth muscle) transition via TGF-β signaling, resulting in recipient EC-derived SMC accumulation as a major mechanism of vascular remodeling during TA. [Read the Full Post]

IgG subclasses determine pathways of anaphylaxis in mice

3412 | Feb 27 2017

Beutier H et al. proposed that the differential expression of inhibitory FcγRIIB on myeloid cells and its differential binding of IgG subclasses controls the contributions of mast cells, basophils, neutrophils, and macrophages to IgG subclass-dependent anaphylaxis. Collectively, our results unravel novel complexities in the involvement and regulation of cell populations in IgG-dependent reactions in vivo. [Read the Full Post]

Relative cytotoxic potencies and cell death mechanisms of α1 -adrenoceptor antagonists in prostate cancer cell lines

2570 | Feb 24 2017

Prazosin and doxazosin demonstrated cytotoxic actions on both castration-resistant PC-3 and androgen-sensitive LNCap prostate cancer cells. The mechanisms involved included changes in a number of proliferation and apoptosis regulatory proteins. The role of autophagy depended on the cell type, but contributed to cell death in PC3 cells. [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

0 | Feb 20 2017

Mathur R, et al.‘s’ results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. [Read the Full Post]

Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus

0 | Feb 10 2017

Cui R et al.‘s’ findings provide a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. [Read the Full Post]

Human UDP-glucuronosyltransferase (UGT) 2B10: Validation of cotinine as a selective probe substrate, inhibition by UGT enzyme selective inhibitors and antidepressant and antipsychotic drugs, and structural determinants of enzyme inhibition

2453 | Feb 09 2017

Pattanawongsa A, et al.'s result indicates that these drugs may perpetrate inhibitory drug-drug interactions when coadministered with compounds that are cleared predominantly by UGT2B10. [Read the Full Post]

AKT and 14-3-3 Regulate Notch4 Nuclear Localization

3354 | Feb 06 2017

Ramakrishnan G, et al.'s findings provide a novel mechanism for Notch4-ICD regulation, suggesting a negative regulatory role for the PI3K-AKT pathway in Notch4 nuclear signaling. [Read the Full Post]

The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid.

3329 | Feb 01 2017

Hiramoto K et al. suggested that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. [Read the Full Post]

Targeting the Neurokinin-1 Receptor Compromises Canonical Wnt Signaling in Hepatoblastoma

2039 | Jan 31 2017

Ilmer M et al. revealed important insight into the molecular mechanisms of the SP/NK1R complex as a critical component in a model of pediatric liver cancer and may support the development of novel therapeutic interventions for HB and other Wnt-activated cancers. [Read the Full Post]

An RNA interference screen identifies new avenues for nephroprotection

2088 | Jan 31 2017

These data shed new light on the mechanisms of stress response in mammalian cells, and open new avenues to reduce the morbidity and mortality associated with renal injury. [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

4607 | Jan 10 2017

Mathur R, et al.'s results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. [Read the Full Post]

Human UDP-glucuronosyltransferase (UGT) 2B10: Validation of cotinine as a selective probe substrate, inhibition by UGT enzyme selective inhibitors and antidepressant and antipsychotic drugs, and structural determinants of enzyme inhibition

2289 | Jan 04 2017

In vitro-in vivo extrapolation of Pattanawongsa A, et al. indicates that these drugs may perpetrate inhibitory drug-drug interactions when coadministered with compounds that are cleared predominantly by UGT2B10. [Read the Full Post]

AKT and 14-3-3 Regulate Notch4 Nuclear Localization

3897 | Dec 29 2016

Ramakrishnan G, et al.'s findings provide a novel mechanism for Notch4-ICD regulation, suggesting a negative regulatory role for the PI3K-AKT pathway in Notch4 nuclear signaling. [Read the Full Post]

Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents

2611 | Dec 28 2016

Zhu J, et al found that compound 26, which exhibited a remarkable metabolic stability in vitro and a favorable antitumor effect in vivo, would serve as a promising lead for the development of new MDR reversal agents. [Read the Full Post]

Paeoniflorin protects diabetic mice against myocardial ischemic injury via the transient receptor potential vanilloid 1/calcitonin gene-related peptide pathway

1521 | Nov 29 2016

Han F et al.’s findings demonstrate that PF protects diabetic mice against MI at least partially via the TRPV1/CaMK/CREB/CGRP signaling pathway. [Read the Full Post]

Tetrandrine has anti-adipogenic effect on 3T3-L1 preadipocytes through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3

1763 | Nov 22 2016

Jang BC et al. showed that tetrandrine has strong anti-adipogenic effect on 3T3-L1 preadipocytes and the effect is largely attributable to the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3. [Read the Full Post]

Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus

4519 | Nov 03 2016

Cui R et al. provided a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. [Read the Full Post]

Levetiracetam mitigates doxorubicin-induced DNA and synaptic damage in neurons

2671 | Oct 27 2016

Manchon JF et al. found that levetiracetam might be part of a valuable new approach for mitigating synaptic damage and, perhaps, for treating cognitive disturbances in cancer patients and survivors. [Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

6000 | Oct 27 2016

Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]

Resveratrol protects CA1 neurons against focal cerebral ischemic reperfusion-induced damage via the ERK-CREB signaling pathway in rats

2368 | Sep 13 2016

Li Z, et al. showed that the NMDA receptor-mediated ERK-CREB signaling pathway might participates in Res-induced neuroprotection in rats with focal cerebral ischemia. [Read the Full Post]

Unexpected role of Notch signaling on directing the trophectoderm lineage in the mouse blastocyst

6629 | Jan 30 2015

Rayon et al. showed that Notch signaling plays a key role in mediating TE-specific expression of Cdx2, though interaction with the transcription factor TEAD4. [Read the Full Post]

The Notch signaling controls maintenance of memory CD4+ T cells

10469 | Dec 16 2014

Recently, Maekawa et al. demonstrated Notch signaling is important for the survival of memory CD4+ T cells by regulating glucose uptake. [Read the Full Post]

MeCP2 S421 phosphorylation mediates neurogenesis via Notch signaling pathway

8836 | Dec 04 2014

Li et al. identified the Notch signaling is involved in the regulation of MeCP2 S421 phosphorylation other than neuronal activity. [Read the Full Post]

Two strategies to overcome eribulin resistance: pharmacokinetic imaging and nanoparticle delivery system

5561 | Nov 17 2014

Laughney et al. developed strategies of pharmacokinetic for to reveal drug-resistant mechanisms, and nanoparticle system to overcome the resistance. [Read the Full Post]

A new neurogenic receptor activator of P2Y1——Up4A

4859 | Nov 13 2014

Recently, researchers from Nevada School of Medicine found a novel factor, Up4A, may contribute in mediating enteric inhibitory neurotransmission of the intestines, acts through P2Y1 receptors and apamin-sensitive small-conductance SK channels. [Read the Full Post]

Notch signaling acts as a key regulator in generation of neurons from neural precursor cells

5834 | Oct 23 2014

Notch signaling plays a central role before asymmetric division and in the fate of Drosophila melanogaster neural precursor cells. It also acts as a critical factor in Numb distribution in neural precursor cells before cleavage. [Read the Full Post]

Tariquidar is a P glycoprotein inhibitor undergoing research

4622 | Jan 27 2014

Tariquidar (XR9576) is a potent and selective noncompetitive inhibitor of P-glycoprotein with Kd of 5.1 nM, reverses drug resistance in MDR cell Lines. [Read the Full Post]

Tariquidar is a P glycoprotein inhibitor undergoing research

4575 | Dec 30 2013

Tariquidar displays high-affinity binding to P-gp with Bmax of 275 pmol/mg. [Read the Full Post]

Zosuquidar is a compound of antineoplastic drug

4218 | Dec 30 2013

Zosuquidar (LY335979) is a potent modulator of P-glycoprotein-mediated multi-drug resistance with Ki of 60 nM. [Read the Full Post]

Brefeldin A used to enhance intracellular cytokine staining signals

3314 | Dec 23 2013

Brefeldin A is a lactone antibiotic and ATPase inhibitor for protein transport with IC50 of 0.2 μM in HCT 116 cells, induces cancer cell differentiation and apoptosis. [Read the Full Post]

LY335979 is a potent inhibitor that contains a cyclopropyldibenzosuberane moiety

4412 | Dec 16 2013

LY335979 competitively inhibits equilibrium binding of vinblastine to Pgp by blocking azidopine photoaffinity labeling of the Pgp in CEM/VLB100 plasma membranes. [Read the Full Post]

Tariquidar is a P glycoprotein inhibitor undergoing research as an adjuvant

4142 | Oct 23 2013

Tariquidar is a potent and selective noncompetitive inhibitor of P-glycoprotein with Kd of 5.1 nM, reverses drug resistance in MDR cell Lines. [Read the Full Post]

MRS2578 is a selective antagonist of P2Y6 nucleotide receptors

3344 | Jul 29 2013

MRS 2578 (10 μM) significant reduces TNF-α–induced proinflammatory gene expression in HMEC-1 cells. [Read the Full Post]

Ouabain isolated from plants is widely used by scientists in in vitro studies

3482 | May 30 2013

In many non rodent species, low concentrations of this substance (i.e., in the subnanomolar range) may stimulate the Na-K-ATPase. The mechanism of the stimulatory effect is not understood and remains controversial. Further, the issue in rodents is more complicated because there are different isoforms of the Na-K-ATPase - some of which are very sensitive to ouabain while others are not. [Read the Full Post]

Ouabain is found in the ripe seeds of African plants

3463 | May 14 2013

It is well understood that the classical mechanism of action of ouabain involves its binding to and inhibition of the plasma membrane Na+/K+-ATPase (sodium pump) especially at the higher concentrations attainable in vitro or with intravenous dosage. [Read the Full Post]

MK 801 has a great deal of potential to be used in research in creating animal models of schizophrenia

3987 | May 10 2013

MK-801 has a great deal of potential to be used in research in creating animal models of schizophrenia. Unlike dopaminergic agonists, which mimic only the positive symptoms of schizophrenia, a single injection of MK801 was successful in modelling both the positive and negative symptoms of schizophrenia. [Read the Full Post]

Bufexamac is a drug used as an anti inflammatory agent on the skin

4168 | Jan 21 2013

The Bufexamac importance of the HGF/c-MET pathway in the control of tissue homeostasis is supported by the well established protective activity of HGF in several degenerative diseases, including progressive nephropathies , liver cirrhosis and lung fibrosis. [Read the Full Post]

LY2140023 is a novel investigational agent for the treatment of schizophrenia

3729 | Jan 18 2013

LY2140023 is a novel investigational agent for the treatment of schizophrenia. A member of a new class of antipsychotic drugs, LY2140023 is still in early stage clinical development. Nevertheless, analysts have hailed it as an exciting new medicine that may herald the arrival of third-generation antipsychotic drugs. [Read the Full Post]

Gamma secretase is a mult subunit protease complex

3566 | Jan 09 2013

The network of tumor blood vessels that perfuse a solid tumor plays a fundamental role in its growth and survival. Not only do the blood vessels feed the Gamma Secretase tumor with oxygen and nutrients through the blood, they also allow for the subsequent removal of cellular waste products. [Read the Full Post]

New and Potent COX receptor inhibitors are available

3827 | Dec 10 2012

PCR amplified cDNA COX Inhibitors fragment containing human EGFR kinase domain from amino acids 696 to 1022 was attached to the C-terminal coding region (3? region) of the glutathione S-transferase gene and the fused DNA fragment is cloned into a baculovirus expression vector pBacPAK8 (Clontech, Palo Alto, CA, USA). [Read the Full Post]

Gamma Secretase were grown in 5 ml of medium

5527 | Nov 28 2012

The cells were pelleted by centrifugation, the medium was Gamma Secretase removed with the drug, and the cells were washed washed with sterile PBS and centrifuged again. [Read the Full Post]

Celecoxib was observed in our in vitro

3648 | Oct 24 2012

EGFR somatic doublet mutations are potentially more frequent than previously understood, with majority of them representing driver driver mutations rather than driver passenger mutations [Read the Full Post]

Oligomycin A CGMP or cAMP in the lysates were by radioimmunoassay

4229 | Oct 23 2012

CGMP or cAMP in the lysates were by radioimmunoassay of cGMP from Amersham or with protein kinase type I muscle beef, each determined. Activity t and PIP3 [Read the Full Post]

RO4929097 – CHECKS NOTCH SIGNALING IN CANCERS

5921 | Mar 20 2012

RO4929097: A GAMMA SECRETASE INHIBITOR: Among well known proteases Gamma secretase is one which is made up of various subunits. This is present in the membrane hence is a protein in membrane which is also capable of cleaving certain transmembrane proteins therefore also known as the intramembrane protease. In case of Alzheimer’s disease amyloid plaques are formed in brain, these plaques are resulted due to the amyloid beta peptide and these peptides are produced due to the action of gamma secretase, this is one of the well known examples of this protease. Presently, we are focusing on the important role of gamma secretase in the Notch protein processing. In case of many cancers and tumors this Notch protein signaling is found to be abnormal, therefore the arresting of this pathway can be an authentic way to get rid of abnormal cell growth. In the light of this idea a novel RO4929097 gamma secretase inhibitor is discovered. The inhibitory effect of this inhibitor has been confirmed by various methods like western blotting. [Read the Full Post]

RO4929097 – TARGETING NOTCH SIGNALING IN CANCER

6816 | Mar 13 2012

RO4929097: INHIBIT GAMMA SECRETASE: Gamma secretase is famous protease consists of several subunits complex. This enzyme is also recognized as inter-membrane protease as it cuts trans-membrane proteins. The most eminent gamma secretase example is breakage of amyloid precursor, a protein to produce amyloid beta peptide which is involved in the formation of amyloid plaques in patient’s brain who suffer with Alzheimer’s disease. In the present situation though, we concentrate on the key role of gamma secretase in the Notch protein processing. It has been found as there is link between anomalous notch signaling and many cancers. Hence the idea of targeting those enzymes which are responsible for the processing of Notch protein became the reason of RO4929097 gamma secretase inhibitor discovery. The inhibiting Notch signaling by using RO4929097 GS inhibitor has been confirmed by protein estimation methods like Biuret method etc. [Read the Full Post]

RO4929097 – CONTROLLING NOTCH SIGNALING IN TUMORS

6914 | Mar 13 2012

Introduction: Gamma secretase Inhibition Gamma secretase is an internal protease enzyme that is a complex of a number of subunits. Its mode of action is to cleave proteins that lie within the membrane-spanning domain, these include the amyloid precursor protein (APP) and the Notch. The Notch signaling pathway processes four different Notch receptors (1, 2, 3 and 4) which span the cell membrane. Upon extracellular interaction with a substrate protein the internal domain is released. This section of the protein then induced a signaling cascade within the cell nucleus to alter gene expression. The function of the various NOTCH proteins is varied but in terms of cancer notch receptors have been demonstrated to be down regulated in basal cells carcinomas and cervical cancers. Notch 1 over-expression is associated with acute T cell leukemia and breast cancer, Notch 3 receptor is over-expressed in 20% of ovarian cancers [5-7] while overexpression of Notch 4 is evident in murine models of breast cancer. The field of research into NOTCH signaling is vast and beyond the scope of this document, simple put there existed evidence that inhibition of aberrant NOTCH over-expression would be an ideal target for chemotherapeutic activity. The development of inhibitors which would affect the action of NOTCH led to the targeting of the Gamma secretase enzyme. Developed by Roche the RO4929097 gamma secretase inhibitor represents a potent novel small molecule that is orally bioavailable. [Read the Full Post]

Yin, L., O. C. Velazquez, et al. (2010). "Notch signaling: emerging molecular targets for cancer therapy." Biochem Pharmacol 80(5): 690-701.

5863 | Jul 13 2011

This article is a review which give a presentation of Notch signal pathway and how the researchers target Notch signal pathway for a cancer therapy. [Read the Full Post]