GPCR & G Protein

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

119 | 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

29 | 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

89 | 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]

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

29 | 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]

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

30 | 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

30 | 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]

Adenosine A1 Receptors Participate in Excitability Changes after Cortical Epileptic Afterdischarges in Immature Rats

20 | Feb 08 2024

Adenosine A1 receptor modulation demonstrated age-dependent effects on postictal potentiation and refractoriness in rats, with A1 agonists suppressing both types of potentiation in younger rats while antagonists augmented delayed potentiation and moderately affected immediate refractoriness, indicating crucial regulatory roles of these receptors in post-seizure responses across different developmental stages. [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

25 | 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

43 | 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

23 | 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]

Tauro-Urso-Deoxycholic Acid Trials in Amyotrophic Lateral Sclerosis: What is Achieved and What to Expect

23 | Feb 01 2024

Phase II studies suggest the safety and efficacy of TUDCA in ALS treatment, with ongoing phase III trials expected to provide a more conclusive understanding of its potential. [Read the Full Post]

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

34 | 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

35 | 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]

Antitumor effect of a small-molecule inhibitor of KRASG12D in xenograft models of mucinous appendicular neoplasms

36 | Jan 25 2024

The profound inhibition of tumor growth in a high-grade PMP xenograft mouse model carrying a KRASG12D mutation by the small-molecule KRASG12D inhibitor MRTX1133 underscores its potent efficacy and supports its potential for clinical translation in treating PMP. [Read the Full Post]

CRISPR screening identifies mechanisms of resistance to KRASG12C and SHP2 inhibitor combinations in non-small cell lung cancer

40 | Jan 23 2024

The study uncovers that while KRASG12C inhibitors initially exhibit promising responses, combining them with SHP2, PI3K, and CDK4/6 inhibitors extends regression in preclinical models, yet resistance emerges via KRASG12C amplification and MAPK/PI3K pathway alterations, with FGFR1 loss sensitizing and PTEN loss rescuing against the KRASG12C/SHP2 inhibition. [Read the Full Post]

Blocking SphK/S1P/S1PR1 axis signaling pathway alleviates remifentanil-induced hyperalgesia in rats

26 | Jan 19 2024

This study demonstrates that blocking the SphK/S1P/S1PR1 axis mitigates remifentanil-induced hyperalgesia by reducing spinal cord inflammation and reactive oxygen species, offering potential avenues for managing opioid-induced pain sensitization. [Read the Full Post]

In vitro pharmacological characterization of standard and new lysophosphatidic acid receptor antagonists using dynamic mass redistribution assay

27 | Jan 19 2024

The use of label-free dynamic mass redistribution assays revealed novel LPA1 inverse agonist CHI and highlighted the potential advantages over traditional calcium mobilization assays in characterizing LPA receptor ligands for diverse therapeutic applications. [Read the Full Post]

High-dose remifentanil exacerbates myocardial ischemia-reperfusion injury through activation of calcium-sensing receptor-mediated pyroptosis

18 | Jan 15 2024

Short-term exposure to high radiofrequency exacerbates myocardial ischemia/reperfusion injury by upregulating calcium-sensing receptors, leading to increased cytosolic calcium levels, ROS production, and subsequent activation of the NLRP3 inflammasome, ultimately promoting pyroptotic cell death. [Read the Full Post]

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

22 | 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]

Evolving views on the first two ligands of the angiotensin II type 2 receptor. From putative antagonists to potential agonists?

24 | Jan 08 2024

The evolving understanding of PD123319's effects challenges its traditional classification as an AT2 receptor antagonist, suggesting potential agonist-like actions at lower doses and highlighting the intricate balance between AT1 and AT2 receptor stimulation within the renin-angiotensin system. [Read the Full Post]

Active natural compounds perturb the melanoma risk-gene network

58 | 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]

LIPH contributes to glycolytic phenotype in pancreatic ductal adenocarcinoma by activating LPA/LPAR axis and maintaining ALDOA stability

22 | Jan 05 2024

The upregulation of LIPH in pancreatic ductal adenocarcinoma drives tumor progression by activating the LPA/LPAR axis, promoting aberrant glycolysis, and maintaining ALDOA stability, offering a potential avenue for a targeted gemcitabine-based combination therapy with limited side effects. [Read the Full Post]

Current evidence for second-line treatment in metastatic renal cell carcinoma after progression to immune-based combinations

25 | Jan 05 2024

The evolving landscape of metastatic renal cell carcinoma treatments, driven by immune checkpoint inhibitor-based combinations in the first line and uncertainties in subsequent therapies, highlights the need for predictive models and ongoing research to guide personalized, effective treatment strategies. [Read the Full Post]

Runx3 Restoration Regresses K-Ras-Activated Mouse Lung Cancers and Inhibits Recurrence

47 | Jan 02 2024

The study's findings suggest that the restoration of RUNX3 presents a promising therapeutic avenue for effectively treating K-RAS-activated lung cancers by regressing tumors and suppressing recurrence through multifaceted pathways, potentially offering a durable response. [Read the Full Post]

Identification of CXCR4 Upregulation in Diffuse Large B-Cell Lymphoma Associated with Prognostic Significance and Clinicopathological Characteristics

23 | Dec 31 2023

The upregulation of CXCR4 in activated B-cell-like DLBCL, associated with poorer prognosis, suggests CXCR4 as a potential therapeutic target, warranting further investigation and potential clinical trials for DLBCL treatment. [Read the Full Post]

Blockade of CCR1 induces a phenotypic shift in macrophages and triggers a favorable antilymphoma activity

32 | Dec 28 2023

Inhibiting CCR1 in B-cell lymphoma's microenvironment reprograms protumor macrophages, diminishes immunosuppression, and presents a promising therapeutic avenue for reshaping the tumor milieu and improving patient outcomes. [Read the Full Post]

Potential role of Acanthamoeba Rab7

55 | Dec 26 2023

The study elucidates the pivotal role of AcRab7 in Acanthamoeba castellanii's phagocytosis, endosomal delivery, and cellular physiology, demonstrating its influence on energy production, cell proliferation, and potential implications for understanding related parasitic diseases. [Read the Full Post]

Heteroplasmic pathogenic m.12315G>A variant in MT-TL2 presenting with MELAS syndrome and depletion of nitric oxide donors

32 | Dec 25 2023

This report highlights a 5-year-old child's neurological regression and stroke-like episodes associated with the MT-TL2 m.12315G>A mitochondrial variant, emphasizing the significance of detailed biochemical analyses and tailored treatments to expand the understanding and management of this rare condition. [Read the Full Post]

Exercise attenuates neuronal degeneration in Parkinson's disease rat model by regulating the level of adenosine 2A receptor

85 | Dec 23 2023

Exercise appears to mitigate Parkinson's disease symptoms in rats by reducing neurodegeneration through a-synuclein aggregation reduction and adenosine 2A receptor modulation, although the co-administration of an adenosine A2A receptor agonist reverses these beneficial effects. [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

43 | 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]

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

19 | 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]

Antineoplastic effects of pharmacological inhibitors of aurora kinases in CSF3RT618I-driven cells

52 | Dec 14 2023

The study demonstrates that aurora kinase inhibitors, particularly reversine, exert significant antineoplastic effects in Ba/F3 cells expressing the CSF3RT618I mutation, reducing cell viability, clonogenicity, and proliferative capacity, while modulating key molecular pathways associated with cell cycle and apoptosis in the context of chronic neutrophilic leukemia (CNL). [Read the Full Post]

TLR4 activation induces inflammatory vascular permeability via Dock1 targeting and NOX4 upregulation

37 | Dec 08 2023

The study demonstrates that the TLR4 inflammatory cascade disrupts vascular integrity by downregulating Dock1 and Elmo1 expression, highlighting Dock1 as a critical target in TLR4-mediated inflammatory lung injury and emphasizing its essential role in maintaining endothelial cell junctional integrity. [Read the Full Post]

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

15 | 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]

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

25 | 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]

DOCK2 is involved in the host genetics and biology of severe COVID-19

33 | Nov 24 2023

A genome-wide association study in a Japanese population identified a specific genetic variant (rs60200309-A) near the DOCK2 gene on chromosome 5, linked to decreased DOCK2 expression in immune cells, revealing its crucial role in the host immune response to SARS-CoV-2 infection and suggesting its potential as a biomarker and therapeutic target for severe COVID-19. [Read the Full Post]

Myeloid-derived growth factor suppresses VSMC dedifferentiation and attenuates postinjury neointimal formation in rats by activating S1PR2 and its downstream signaling

14 | Nov 20 2023

The study demonstrates that Myeloid-derived growth factor (MYDGF) alleviates neointimal formation in rat carotid arteries post balloon injury by inhibiting vascular smooth muscle cell dedifferentiation through the S1PR2-RhoA-G/F-actin-MRTF-A signaling pathway, suggesting its potential as a therapeutic target for preventing restenosis after angioplasty. [Read the Full Post]

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

55 | 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

34 | 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]

Peripheral Activation of Formyl Peptide Receptor 2/ALX by Electroacupuncture Alleviates Inflammatory Pain by Increasing Interleukin-10 Levels and Catalase Activity in Mice

24 | Nov 17 2023

The study demonstrates that the antihyperalgesic effect of electroacupuncture in a persistent inflammatory pain model may be associated with increased IL-10 levels and enhanced catalase activity in inflamed tissue, potentially mediated by peripheral FPR2/ALX activation. [Read the Full Post]

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

34 | 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]

Inhibition of exchange proteins directly activated by cAMP as a strategy for broad-spectrum antiviral development

22 | Nov 14 2023

The study demonstrates that EPAC antagonists like ESI-09 hold promise as broad-spectrum antiviral therapies, offering robust protection against various viruses and potential contributions to pandemic preparedness. [Read the Full Post]

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

92 | 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]

Pharmacological Characterization of P626, a Novel Dual Adenosine A2A/A2B Receptor Antagonist, on Synaptic Plasticity and during an Ischemic-like Insult in CA1 Rat Hippocampus

25 | Nov 02 2023

The newly synthesized dual A2AAR/A2BAR antagonist, P626, demonstrated the ability to prevent A2AAR- and A2BAR-mediated effects and delay anoxic depolarization in a concentration-dependent manner, potentially making it a promising neuroprotective compound for stroke treatment. [Read the Full Post]

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

60 | 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]

Identification of Tau-Tubulin Kinase 1 Inhibitors by Microfluidics-based Mobility Shift Assay from a Kinase Inhibitor Library

73 | Oct 29 2023

This study identified a peptide substrate for human TTBK1 and developed a microfluidics-based assay, enabling the screening of kinase inhibitors and the potential development of novel hTTBK1 inhibitors for Alzheimer's disease prevention. [Read the Full Post]

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

44 | 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]

Effect of budesonide on pulmonary activity of multidrug resistance-associated protein 1 assessed with PET imaging in rats

20 | Oct 23 2023

Intratracheal aerosolized budesonide, even at a dose approximately five times higher than the maximum clinical dose, did not affect pulmonary MRP1 activity in rats, suggesting no impact on the MRP1-mediated detoxifying capacity of the lungs, while the model MRP1 inhibitor MK571 exhibited a significant inhibitory effect. [Read the Full Post]

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

22 | 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]

Pituitary Adenylate Cyclase Activating Polypeptide Inhibits A10 Dopamine Neurons and Suppresses the Binge-like Consumption of Palatable Food

35 | Oct 19 2023

Pituitary adenylate cyclase-activating polypeptide (PACAP) activates PAC1 receptors and KATP channels to inhibit A10 dopamine neurons in the ventral tegmental area (VTA), resulting in a sex-dependent suppression of binge-like consumption and contributing to the regulation of energy homeostasis through the hedonic energy balance circuitry. [Read the Full Post]

Platelet zinc status regulates prostaglandin-induced signaling, altering thrombus formation

23 | Oct 18 2023

Zinc chelation potentiates platelet prostacyclin (PGI2) signaling, resulting in increased inhibition of platelet activation, aggregation, and thrombus formation. [Read the Full Post]

Current Treatments for Patients with Genetic Obesity

90 | 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

65 | 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

32 | 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)

18 | 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]

APX-115, a pan-NADPH oxidase inhibitor, protects development of diabetic nephropathy in podocyte specific NOX5 transgenic mice

0 | Oct 02 2023

APX-115, a pan-NOX inhibitor, shows potential as a promising therapeutic agent for the treatment of diabetic nephropathy by improving pancreatic beta cell function, reducing lipid levels, restoring kidney damage markers, and exerting anti-inflammatory effects. [Read the Full Post]

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

65 | 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]

Bone impact after two years of low-dose oral contraceptive use during adolescence

62 | Sep 29 2023

The present study indicates that the use of combined hormonal contraceptives in healthy adolescents is associated with compromised bone mass acquisition, with a more pronounced negative impact observed in those using contraceptives containing 30 μg of Ethinylestradiol. [Read the Full Post]

Post-Marketing Use of Teduglutide in a Large Cohort of Adults with Short Bowel Syndrome-Associated Chronic Intestinal Failure: Evolution and Outcomes

50 | Sep 26 2023

This real-life study assessing teduglutide initiation and outcomes in SBS-CIF patients demonstrated its efficacy in reducing parenteral support volume and indicated a higher response rate in incident patients, suggesting a potential benefit in early treatment. [Read the Full Post]

A phase 1 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of danuglipron (PF-06882961), an oral small-molecule glucagon-like peptide-1 receptor agonist, in Japanese adults with type 2 diabetes mellitus

27 | Sep 24 2023

In Japanese participants with type 2 diabetes mellitus, the oral small-molecule glucagon-like peptide-1 receptor agonist danuglipron demonstrated dose-proportional increases in exposure, significantly reduced glycaemic parameters and body weight, and exhibited a safety profile consistent with its mechanism of action. [Read the Full Post]

Discovery of Novel 5,6-Dihydro-1,2,4-triazine Derivatives as Efficacious Glucagon-Like Peptide-1 Receptor Agonists

59 | Sep 24 2023

The study introduces compound 42, a novel 5,6-dihydro-1,2,4-triazine derivative, as a highly potent and selective GLP-1R agonist with improved efficacy, selectivity, and duration of action compared to danuglipron, demonstrating its potential for the treatment of type 2 diabetes mellitus and obesity. [Read the Full Post]

A Case of Dulaglutide-Induced Vaginal Bleed

31 | Sep 20 2023

Severe vaginal bleeding, a rare side effect of Dulaglutide, was observed in a perimenopausal female with type 2 diabetes mellitus, underscoring the importance of post-market surveillance to identify uncommon adverse reactions not seen in clinical trials. [Read the Full Post]

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

62 | 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]

Detection of Ras nanoclustering-dependent homo-FRET using fluorescence anisotropy measurements

64 | Sep 12 2023

Fluorescence anisotropy-based homo-FRET measurements using Ras-derived constructs labeled with a single fluorescent protein provide a sensitive and advantageous approach to investigate Ras nanoclustering and assess modulators of functional Ras membrane organization. [Read the Full Post]

Phloretin Improves Ultrafiltration and Reduces Glucose Absorption during Peritoneal Dialysis in Rats

27 | Sep 10 2023

The study found that blocking facilitative glucose channels with phloretin reduced glucose absorption and improved ultrafiltration efficiency in peritoneal dialysis, suggesting it as a promising approach for therapeutic interventions in this context. [Read the Full Post]

Phase II drugs under clinical investigation for the treatment of chronic constipation

108 | Sep 10 2023

New investigational drugs for the treatment of chronic constipation show promise in terms of improved effectiveness and tolerability, but further clinical trials with larger sample sizes and longer durations are needed to establish their efficacy and safety. [Read the Full Post]

Targeting of SOS1: from SOS1 Activators to Proteolysis Targeting Chimeras

0 | Sep 08 2023

Research has led to the development of targeted therapies, including KRAS G12C-directed drugs and SOS1 inhibitors, with potential for treating specific mutations in lung, pancreatic, and colon cancers. [Read the Full Post]

Early changes in circulating cell free KRAS G12C predicts response to adagrasib in KRAS mutant non-small cell lung cancer patients

92 | Sep 06 2023

Early changes in circulating tumor DNA (ctDNA) levels of KRAS G12C, assessed approximately three weeks into treatment, can predict the likelihood of a favorable objective clinical response in patients with advanced, KRAS G12C mutant lung cancer. [Read the Full Post]

The Therapeutic Landscape for KRAS-Mutated Colorectal Cancers

52 | Sep 06 2023

The development of selective inhibitors targeting KRAS mutations, such as the FDA-approved Sotorasib and Adagrasib, has shown promise in treating colorectal cancer, but further research is needed to optimize their efficacy and overcome treatment resistance. [Read the Full Post]

Targeting KRAS in pancreatic cancer: Emerging therapeutic strategies

76 | Aug 30 2023

This chapter provides an overview of KRAS biochemistry, signaling pathways, different mutations, emerging KRAS-targeted therapies, combination strategies, challenges in KRAS targeting, and future directions with a specific emphasis on pancreatic cancer. [Read the Full Post]

Clinical Characterization of Targetable Mutations (BRAF V600E and KRAS G12C) in Advanced Colorectal Cancer-A Nation-Wide Study

98 | Aug 30 2023

The retrospective analysis revealed that BRAF V600E mutation in metastatic colorectal cancer is associated with factors such as female sex, right colon primary location, and specific histological features, while KRAS G12C mutation is linked to left colon primary tumors and brain metastases, suggesting potential therapeutic targets and the need for further investigation. [Read the Full Post]

Evaluation of KRASG12C inhibitor responses in novel murine KRASG12C lung cancer cell line models

65 | Aug 30 2023

The generation of three novel murine KRASG12C-driven lung cancer cell lines provides valuable models for studying and improving therapeutic combination strategies with KRASG12C inhibitors. [Read the Full Post]

Targeting of SOS1: from SOS1 Activators to Proteolysis Targeting Chimeras

77 | Aug 29 2023

The development of KRAS G12C-directed drugs and SOS1 inhibitors represents promising approaches for targeting mutated oncogenes in lung, pancreatic, and colon cancers. [Read the Full Post]

CXCR3 antagonist AMG487 ameliorates experimental autoimmune prostatitis by diminishing Th1 cell differentiation and inhibiting macrophage M1 phenotypic activation

42 | Aug 20 2023

The study demonstrates that treatment with the CXCR3 antagonist AMG487 can effectively alleviate inflammation and pelvic pain in a mouse model of experimental autoimmune prostatitis (EAP), suggesting its potential as a therapeutic agent for the prevention and treatment of chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS). [Read the Full Post]

[Roles of the CXCR1/CXCL8 axis in abnormal proliferation of bile duct epithelial cells in primary biliary cholangitis]

68 | Aug 17 2023

The study concludes that the CXCR1/CXCL8 axis plays a role in the abnormal proliferation of bile duct epithelial cells in primary biliary cholangitis (PBC) through the activation of NF-κB and ERK pathways. [Read the Full Post]

Reparixin improves survival in critically ill and transplant patients: A meta-analysis

41 | Aug 16 2023

Reparixin, an anti-inflammatory drug inhibiting interleukin 8 (IL-8) activity, was found to improve survival in critically ill or transplant patients, including both COVID-19 and non-COVID-19 patients, without increasing the risk of infection, according to a meta-analysis of nine randomized controlled trials. [Read the Full Post]

C-C motif chemokine receptor 2 inhibition reduces liver fibrosis by restoring the immune cell landscape

36 | Aug 08 2023

Cenicriviroc (CVC) treatment and CCR2 deletion alleviate liver fibrosis by restoring the immune cell landscape, inhibiting the hepatic accumulation of inflammatory macrophages and neutrophils, and suppressing profibrotic gene transcription through inactivation of the CCR2-STAT1/NFκB/ERK signaling pathways. [Read the Full Post]

Tropifexor plus cenicriviroc combination versus monotherapy in non-alcoholic steatohepatitis: Results from the Phase 2b TANDEM study

57 | Aug 08 2023

The combination therapy of tropifexor (TXR) and cenicriviroc (CVC) did not show significant additional efficacy compared to respective monotherapies in terms of alanine aminotransferase (ALT) levels, body weight, or histological endpoints in the treatment of non-alcoholic steatohepatitis (NASH) in a phase 2b study. [Read the Full Post]

Educational level-dependent melanoma awareness in a high-risk population in Switzerland

83 | Aug 07 2023

The study revealed that melanoma patients had a higher tendency to use a higher sun protection factor (SPF) compared to at-risk patients, emphasizing the significance of UV protection in melanoma prevention. [Read the Full Post]

Senescent Human Pancreatic Stellate Cells Secrete CXCR2 Agonist CXCLs to Promote Proliferation and Migration of Human Pancreatic Cancer AsPC-1 and MIAPaCa-2 Cell Lines

54 | Aug 07 2023

Senescent pancreatic stellate cells (PSCs) and their secreted chemokines, such as CXCLs, play a significant role in promoting the proliferation and migration of pancreatic cancer cells, suggesting their potential as therapeutic targets for pancreatic cancer treatment. [Read the Full Post]

A PDX model combined with CD-DST assay to evaluate the antitumor properties of KRpep-2d and oxaliplatin in KRAS (G12D) mutant colorectal cancer

61 | Aug 06 2023

The combination of patient-derived xenograft (PDX) models and the collagen gel droplet embedded culture drug sensitivity test (CD-DST) offers a comprehensive and feasible approach for evaluating the antitumor properties of compounds, as demonstrated by the significant inhibitory effects of oxaliplatin but lack of effectiveness of KRpep-2d in both tests. [Read the Full Post]

Platelet-derived lysophosphatidic acid mediated LPAR1 activation as a therapeutic target for osteosarcoma metastasis

51 | Jul 30 2023

Targeting the LPA-LPAR1 axis shows promise as a therapeutic intervention for advanced osteosarcoma by inhibiting invasion and metastasis of the cancer cells. [Read the Full Post]

Beyond Weight Loss: Added Benefits Could Guide the Choice of Anti-Obesity Medications

64 | Jul 26 2023

This comprehensive review explores the added benefits and drawbacks of approved and upcoming centrally-acting anti-obesity drugs, highlighting their potential for personalized, pharmacological management of obesity and its associated complications. [Read the Full Post]

Comparative Effects of Glucose-Lowering Medications on Kidney Outcomes in Type 2 Diabetes: The GRADE Randomized Clinical Trial

30 | Jul 25 2023

The Glycemia Reduction Approaches in Diabetes (GRADE) trial found no significant differences in kidney outcomes when comparing the addition of different glucose-lowering medications to metformin for glycemic management in individuals with type 2 diabetes. [Read the Full Post]

Matching-Adjusted Indirect Comparisons of Diroximel Fumarate, Ponesimod, and Teriflunomide for Relapsing Multiple Sclerosis

41 | Jul 24 2023

The analysis comparing Diroximel fumarate (DRF) to Ponesimod (PON) and Teriflunomide (TERI) in the treatment of relapsing multiple sclerosis did not find strong evidence of differences in most clinical and radiological outcomes between DRF and PON, but showed improved efficacy of DRF compared to TERI for all outcomes except absence of new/newly enlarging T2 lesions. [Read the Full Post]

Oncogenic KRAS G12C: Kinetic and redox characterization of covalent inhibition

46 | Jul 21 2023

The recent study reveals that the C12 thiol in KRASG12C exhibits a depressed pKa and susceptibility to chemical ligation, as well as oxidation, providing insights for drug discovery and indicating the occurrence of unknown biological consequences. [Read the Full Post]

Proof of concept for poor inhibitor binding and efficient formation of covalent adducts of KRASG12C and ARS compounds

63 | Jul 21 2023

This computational study provides a comprehensive understanding of the reaction mechanism and kinetic constants involved in the covalent binding of ARS-853 to the KRASG12C·GDP complex, offering insights into the design of selective covalent inhibitors for challenging RAS-like proteins. [Read the Full Post]

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

79 | 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]

Mortality trends of aortic stenosis in high-income countries from 2000 to 2020

48 | Jul 18 2023

This study investigates recent mortality trends from aortic stenosis among eight high-income countries, revealing an increase in crude mortality rates but shifts towards decreasing trends in age-standardized rates in three countries and among individuals aged ≥80 years. [Read the Full Post]

Efficacy and safety of sotagliflozin in patients with type 2 diabetes and stage 3 chronic kidney disease

58 | Jul 18 2023

The study found that sotagliflozin, at a dose of 400 mg but not 200 mg, significantly reduced HbA1c levels compared to placebo after 26 weeks in adults with type 2 diabetes and stage 3 chronic kidney disease, while both doses showed reductions in urine albumin-creatinine ratio at week 26, but not sustained at week 52, and the safety profile was similar to previous reports. [Read the Full Post]

Adenosine A2A Receptors Shut Down Adenosine A1 Receptor-Mediated Presynaptic Inhibition to Promote Implementation of Hippocampal Long-Term Potentiation

82 | Jul 18 2023

Activation of A2A receptors dampens the inhibitory effects of A1 receptors, enabling the implementation of hippocampal long-term potentiation (LTP) during high-frequency induction. [Read the Full Post]

Biomarker-Based Prediction of Recurrent Ischemic Events in Patients With Acute Coronary Syndromes

65 | Jul 16 2023

This study developed and validated an 8-item biomarker-based prediction score, named ABC-ACS ischemia, for assessing the 1-year risk of cardiovascular death or myocardial infarction in patients with acute coronary syndrome undergoing percutaneous coronary intervention. [Read the Full Post]

Higher efficacy of Etoposide + Cytarabine Plus Pegfilgrastim in poorly mobilizing Multiple Myeloma and lymphoma Patients

64 | Jul 13 2023

The retrospective analysis suggests that chemo-mobilization with etoposide, cytarabine, and pegfilgrastim is a highly effective and tolerable strategy for mobilizing hematopoietic stem cells in poorly mobilizing patients with multiple myeloma (MM) or lymphoma. [Read the Full Post]

AMD3100-mediated CXCR4 inhibition impairs development of primary lymphoma of the central nervous system

131 | Jul 13 2023

The inhibition of CXCR4-CXCL12 interactions by AMD3100 in primary lymphoma of the central nervous system (PCNSL) downregulates CD200 expression in lymphoma cells, leading to increased microglial activation, impaired lymphoma cell invasion, and reduced tumor size, suggesting the potential therapeutic utility of AMD3100 in PCNSL. [Read the Full Post]

Empagliflozin and sacubitril/valsartan reverse methotrexate cardiotoxicity by repressing oxidative stress and hypoxia in heart embryonic H9c2 cardiomyocytes - the role of morphology of mitochondria observed on electron microscopy

73 | Jul 12 2023

S/V and EMPA treatment demonstrated significant reductions in HIF-1α levels and oxidative stress markers, along with increased antioxidant parameters and improved mitochondria morphology in H9c2 rat embryonic cardiomyocyte cells. [Read the Full Post]

Formaldehyde exacerbates asthma in mice through the potentiation of HIF-1α-mediated pro-inflammatory responses in pulmonary macrophages

29 | Jul 08 2023

The study revealed that formaldehyde exposure exacerbates asthma by enhancing HIF-1α-mediated inflammatory responses in macrophages, indicating the potential universal role of formaldehyde-induced macrophage metabolic and functional alterations in inflammatory or allergic diseases. [Read the Full Post]

Exploring Synthetic Strategies for 1H-Indazoles and Their N-Oxides: Electrochemical Synthesis of 1H-Indazole N-Oxides and Their Divergent C-H Functionalizations

76 | Jul 08 2023

The research study describes a versatile electrochemical strategy for the selective synthesis of 1H-indazole N-oxides and their subsequent C-H functionalization, demonstrating its potential for the synthesis of diverse pharmaceutical molecules. [Read the Full Post]

Molecular and neuroimmune pharmacology of S1P receptor modulators and other disease-modifying therapies for multiple sclerosis

33 | Jul 07 2023

Multiple sclerosis (MS) is a neurological disease where immune-mediated damage to the central nervous system (CNS) occurs, and while disease-modifying therapies primarily target immunomodulation, sphingosine 1-phosphate receptor (S1PR) modulators like fingolimod also exhibit direct effects on the CNS, potentially reducing neurodegenerative consequences. [Read the Full Post]

Long non‑coding RNA LINC01960‑201 hinders decidualization of endometrial stromal cell in endometriosis: Relevance to endometrial receptivity

131 | Jul 03 2023

The study suggests that LINC01960-201 may play a regulatory role in the decidualization of endometrial stromal cells in women with endometriosis during the window of implantation, potentially affecting endometrial receptivity and recurrent abortions. [Read the Full Post]

The effect of sex on retinopathy of prematurity severity among premature mixed-sex multiple gestation infants

41 | Jun 29 2023

This retrospective study of 68 premature infants found no significant difference between male and female mixed-sex multiple gestation infants in terms of the most severe stage of retinopathy of prematurity (ROP) developed or the need for ROP treatment, but males received treatment at an earlier postmenstrual age (PMA) despite females having lower birthweight and slower growth velocity. [Read the Full Post]

Identifying a selective inhibitor of autophagy that targets ATG12-ATG3 protein-protein interaction

47 | Jun 29 2023

Compound 189, identified through a high throughput compound screen, selectively inhibits the ATG12-ATG3 protein-protein interaction involved in autophagy, demonstrating potential as a therapeutic drug for autophagy-dependent tumors and inflammation. [Read the Full Post]

Anna Karenina principle in personalized treatment of bladder cancer according to oncogram: which drug for which patient?

27 | Jun 28 2023

The ex vivo application of chemotherapy, immunotherapy, and targeted agents using the oncogram method showed higher good response rates compared to the control group in bladder cancer patients, with variations observed on a per-patient basis. [Read the Full Post]

Targeting CXCL1 chemokine signaling for treating cisplatin ototoxicity

63 | Jun 20 2023

This study demonstrates that inhibiting the CXCL1-CXCR2 pathway through trans-tympanic administration of SB225002 or CXCR2 siRNA protects against cisplatin-induced hearing loss, preserves hair cell integrity, and reduces the expression of inflammatory mediators associated with ototoxicity. [Read the Full Post]

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

87 | Jun 05 2023

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

A covalent inhibitor of K-Ras(G12C) induces MHC class I presentation of haptenated peptide neoepitopes targetable by immunotherapy

84 | Jun 04 2023

The study demonstrates that covalent drugs that alkylate mutated residues on oncoproteins can generate unique MHC-I-restricted neoantigens, which can be targeted with a bispecific T cell engager construct to elicit a cytotoxic T cell response against cancer cells, including those resistant to direct inhibition. [Read the Full Post]

Four-Component Strain-Release-Driven Synthesis of Functionalized Azetidines

29 | May 30 2023

This passage describes a successful and rapid multicomponent [1,2]-Brook rearrangement/strain-release-driven anion relay sequence for the modular synthesis of substituted azetidines, which was demonstrated through the 4-step synthesis of the EP2 receptor antagonist PF-04418948. [Read the Full Post]

Repurposing drugs against Alzheimer's disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD?

0 | May 28 2023

Recent studies suggest that the FDA-approved drug fingolimod, which binds to sphingosine-1-phosphate receptors and was originally approved for multiple sclerosis, could potentially reverse synaptic deficits and memory dysfunction in Alzheimer's disease mouse models even when treatment is started after onset of symptoms. [Read the Full Post]

Monitoring recovery after CNS demyelination, a novel tool to de-risk pro-remyelinating strategies

19 | May 28 2023

The study uses a Xenopus laevis transgenic model of conditional demyelination to test candidate molecules for promoting remyelination, correlating functional and clinical performance measures with histopathological parameters to identify potential therapies. [Read the Full Post]

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

38 | 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]

Solubilization, purification, and ligand binding characterization of G protein-coupled receptor SMO in native membrane bilayer using styrene maleic acid copolymer

58 | May 21 2023

The study demonstrates the use of SMA-nanodiscs to solubilize and purify the SMO transmembrane domain in a native-like lipid environment for investigating the structure, function, and drug development of SMO proteins. [Read the Full Post]

Bifidobacterium pseudocatenulatum-Mediated Bile Acid Metabolism to Prevent Rheumatoid Arthritis via the Gut-Joint Axis

21 | May 14 2023

The study found that Bifidobacterium pseudocatenulatum protected against joint damage in a mouse model of rheumatoid arthritis by reshaping gut microbial composition and increasing bile acid metabolism, suggesting that probiotics could be an effective preventative therapy. [Read the Full Post]

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

32 | 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

47 | 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]

TXA2 mediates LPA1-stimulated uterine contraction in late pregnant mouse

14 | May 09 2023

LPA1 stimulation induces contractions in late pregnant mouse uterus through the TXA2 pathway and may have clinical applications in inducing labor in uterine dysfunctions/dystocia. [Read the Full Post]

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

51 | 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]

Insulin can up-regulate LC-PUFA biosynthesis with the involvement of Srebp-1c and stimulatory protein 1 (Sp1) in marine teleost Siganus canaliculatus

46 | May 07 2023

The study found that insulin up-regulates long-chain polyunsaturated fatty acid biosynthesis in rabbitfish through the involvement of transcription factors Srebp-1c and Sp1, as demonstrated in a hepatocyte cell line. [Read the Full Post]

Effects of Ertugliflozin on Kidney Outcomes in Patients With Heart Failure at Baseline in the Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes (VERTIS CV) Trial

37 | May 04 2023

The post hoc analysis of the VERTIS CV trial found that the beneficial effects of ertugliflozin on kidney outcomes were not affected by baseline heart failure status in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. [Read the Full Post]

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

76 | 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

32 | 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]

Effect of FTY-720 on Pulmonary Fibrosis in Mice via the TGF-β1 Signaling Pathway and Autophagy

24 | Apr 30 2023

FTY-720 was found to inhibit the TGF-β1 pathway and up-regulate autophagy, resulting in attenuation of disorganization of alveolar tissue and collagen deposition, and reduced levels of inflammatory cytokines and protein expressions in lung tissue, indicating its potential as a treatment target for pulmonary fibrosis. [Read the Full Post]

Repurposing drugs against Alzheimer's disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD?

22 | Apr 30 2023

FTY720, an FDA-approved drug for the treatment of multiple sclerosis, shows promise in reversing synaptic deficits and memory dysfunction in Alzheimer's disease mouse models, and could be a potential disease modifying anti-AD drug. [Read the Full Post]

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

126 | 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

45 | 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]

Fabricating transdermal film formulations of montelukast sodium with improved chemical stability and extended drug release

67 | Apr 23 2023

This research developed a transdermal delivery system for Montelukast Sodium using SA and LS-based films as a controlled release drug delivery system, demonstrating the potential to improve bioavailability and providing a better mode of drug delivery for pediatric and elderly patients. [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

94 | 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]

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

98 | 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]

5-Oxoproline Enhances 4-Hydroxytamoxifen-induced Cytotoxicity by Increasing Oxidative Stress in MCF-7 Breast Cancer Cells

65 | Apr 15 2023

The study found that 5-oxoproline (5-OP) enhances 4-hydroxytamoxifen (4-OHT)-induced cytotoxicity in estrogen receptor (ER)-positive breast cancer cells under normal glucose conditions, while the selective monocarboxylate transporter (MCT) 4 inhibitor Bindarit decreased 4-OHT sensitivity, and MCT1 expression increased under normal glucose conditions. [Read the Full Post]

TRPM4 gene variation associated with climatic conditions in Chinese cattle

52 | Apr 15 2023

The study suggests that a missense mutation in the TRPM4 gene is associated with heat tolerance in Chinese cattle and could be a candidate locus for further investigation. [Read the Full Post]

Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography

47 | Apr 15 2023

This study demonstrates that Hedgehog and Notch signalling pathways modulate osteoblast differentiation and regulate receptor expression on nanostructured titanium surfaces, with synergistic effects observed with the combination of Hedgehog activation and Notch inhibition. [Read the Full Post]

GW-2974 and SCH-442416 modulators of tyrosine kinase and adenosine receptors can also stabilize human telomeric G-quadruplex DNA

96 | Apr 13 2023

GW-2974 and SCH-442416 could stabilize human telomeric G-quadruplex DNA in addition to their known tyrosine kinase and adenosine receptor modulation properties, suggesting that stabilizing G-quadruplex DNA could be a potential mechanism underlying their anti-cancer activity. [Read the Full Post]

Papain Exerts an Anti-atherosclerosis Effect with Suppressed MPA-mediated Foam Cell Formation by Regulating the MAPK and PI3K/Akt-NF-κB Pathways

125 | Apr 13 2023

The study found that papain inhibits MPA-induced foam cell formation by inactivating the MAPK and PI3K/Akt-NF-κB pathways, thereby exerting an anti-AS effect. [Read the Full Post]

Pirfenidone suppresses tumor necrosis factor-alpha, enhances interleukin-10 and protects mice from endotoxic shock

86 | Apr 12 2023

The study found that pirfenidone provided prophylactic and therapeutic benefits for murine endotoxic shock by inhibiting pro-inflammatory cytokines, enhancing interleukin-10, and suppressing apoptotic cells and TGF-beta1 in the liver. [Read the Full Post]

Potentiation of ASIC currents by lysophosphatidic acid in rat dorsal root ganglion neurons

23 | Apr 11 2023

LPA enhances ASIC-mediated electrophysiological activity and nociception via a LPA1 receptor and PKC signaling pathway, providing a novel peripheral mechanism underlying pain sensitization. [Read the Full Post]

Inhaled pirfenidone solution (AP01) for IPF: a randomised, open-label, dose-response trial

67 | Apr 11 2023

The phase 1b trial evaluated the safety, tolerability, and efficacy of inhaled pirfenidone in patients with IPF and showed that the treatment was well-tolerated and may be a safe and effective alternative to oral pirfenidone or nintedanib. [Read the Full Post]

In vitro pharmacological profile of KW-6356, a novel adenosine A2A receptor antagonist/inverse agonist

34 | Apr 06 2023

The study found that KW-6356 is a potent and selective adenosine A2A receptor antagonist/inverse agonist with insurmountable antagonism, while istradefylline exhibits surmountable antagonism, and crystallography explains the differences in their pharmacological properties. [Read the Full Post]

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

52 | Apr 06 2023

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

The Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Improving Morbidity and Mortality of Heart Failure: A Systematic Review

65 | Apr 04 2023

SGLT2 inhibitors have shown a beneficial effect in reducing cardiovascular mortality and morbidity in patients with type 2 diabetes mellitus and may have a broader application beyond diabetes. [Read the Full Post]

Modeling drug-induced liver injury and screening for anti-hepatofibrotic compounds using human PSC-derived organoids

120 | Mar 27 2023

Human liver organoids derived from pluripotent stem cells have the potential to serve as a preclinical model for drug safety testing and anti-fibrotic drug screening. [Read the Full Post]

Investigation of the Pharmacokinetics and Metabolic Fate of Fasiglifam (TAK-875) in Male and Female Rats Following Oral and Intravenous Administration

96 | Mar 27 2023

Fasiglifam has good oral bioavailability and is extensively metabolized in rats, with a novel biotransformation observed and sex-related differences in drug elimination. [Read the Full Post]

Hyponatremia Associated with Congestive Heart Failure: Involvement of Vasopressin and Efficacy of Vasopressin Receptor Antagonists

32 | Mar 25 2023

Hyponatremia is a common finding in congestive heart failure patients due to AVP-induced water retention, and its presence predicts poor outcomes, but the most effective treatment strategies remain unclear. [Read the Full Post]

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

61 | Mar 23 2023

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

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

46 | 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]

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

105 | 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]

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

28 | 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]

Multivariate Chemometric Comparison of Forced Degradation and Electrochemical Oxidation LC-MS Profiles of Maraviroc

72 | Mar 12 2023

The study found that maraviroc is susceptible to UVA, H2O2, and electrochemical degradation, and suggests that electrochemical methods can be used as a supplement to forced degradation procedures for a quicker and relatively low-cost alternative. [Read the Full Post]

TGFβ1+CCR5+ neutrophil subset increases in bone marrow and causes age-related osteoporosis in male mice

42 | Mar 12 2023

The study suggests that reducing the numbers of TGFβ1+CCR5+ neutrophils in the bone marrow, potentially through the use of a CCR5 antagonist like maraviroc, could be a treatment for age-related osteoporosis. [Read the Full Post]

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

66 | 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

57 | 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]

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

40 | 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]

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

135 | 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

161 | 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

42 | 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]

Dapagliflozin protects against dilated cardiomyopathy progression by targeting NLRP3 inflammasome activation

47 | Feb 25 2023

Dapagliflozin, a SGLT2 inhibitor, improves cardiac function in doxorubicin-induced dilated cardiomyopathy by suppressing the activation of the NLRP3 inflammasome through decreased p38-dependent TLR4 expression. [Read the Full Post]

Metabolomic profiling in kidney cells treated with a sodium glucose-cotransporter 2 inhibitor

17 | Feb 25 2023

Our study found that high glucose conditions in kidney cells altered the metabolomic profile, and treatment with SGLT2 inhibitor dapagliflozin led to significant changes in the levels of metabolites such as asparagine, PC ae C34:1 and PC ae C36:2 in tubular epithelial cells, and PC aa C32:0 in podocytes, which affected multiple metabolic pathways. [Read the Full Post]

Staurosporine analogues from microbial and synthetic sources and their biological activities

95 | 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]

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

83 | 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

41 | 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

94 | 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

71 | 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

96 | 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

64 | 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]

Early identification of a 12-bp tandem duplication in TNFRSF11A encoding receptor activator of nuclear factor-kappa B (RANK): Clinical characterization and response to bisphosphonate therapy

58 | Feb 15 2023

A young girl with early-onset deafness, progressive external tooth root resorption, and increased bone turnover due to a 12-bp duplication within exon 1 of TNFRSF11A was successfully treated with bisphosphonates, preventing further skeletal disease. [Read the Full Post]

The effects of neoadjuvant zoledronic acid in breast cancer patients: A meta-analysis of randomized controlled trials

76 | Feb 15 2023

Our study showed that adding Zoledronic acid (ZA) to neoadjuvant therapy for breast cancer did not improve the pathological complete response rate and resulted in worse mortality compared to the control group, but subgroup analysis revealed a potential benefit for postmenopausal women and patients with triple-negative BC, warranting further investigation. [Read the Full Post]

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

96 | 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

125 | 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]

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

74 | 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

64 | 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]

Interactive webtool for analyzing drug sensitivity and resistance associated with genetic signatures of cancer cell lines

127 | Jan 19 2023

Myriam Boeschen et al. found support for the described sensitivity of H1047 mutants to GSK690693 targeting the AKT pathway. [Read the Full Post]

CRC Therapy Identifies Indian Hedgehog Signaling in Mouse Endometrial Epithelial Cells and Inhibition of Ihh-KLF9 as a Novel Strategy for Treating IUA

31 | Jan 12 2023

Xinhao Zhou et al. suggested a promising application of hedgehog inhibitors as a targeted drug in the IUA clinic. [Read the Full Post]

APX-115, a pan-NADPH oxidase inhibitor, protects development of diabetic nephropathy in podocyte specific NOX5 transgenic mice

68 | Dec 15 2022

Eun Soo Lee et al. suggested that APX-115 might be a promising therapeutic agent for the treatment of DN because of its pan-NOX inhibitory activity, including its NOX5 inhibitory activity, and also owing to its anti-inflammatory effect. [Read the Full Post]

Asthma-related inflammation promotes lung metastasis of breast cancer cells through CCL11-CCR3 pathway

14 | Dec 09 2022

S Bekaert et al. thought that asthma related inflammation in lungs might be a risk factor for lung metastasis in breast cancer patients. [Read the Full Post]

Novel Approaches in Non-Melanoma Skin Cancers-A Focus on Hedgehog Pathway in Basal Cell Carcinoma (BCC)

53 | Nov 16 2022

Paulina Chmiel et al. thought that a central role in the development of BCC was played by the Hedgehog (Hh) signalling pathway. [Read the Full Post]

Current approaches and strategies to identify Hedgehog signaling pathway inhibitors for cancer therapy

76 | Nov 15 2022

Zifan Feng et al. gave a systematic overview of the current status and characteristics of various approaches to developing the Hedgehog pathway inhibitors. [Read the Full Post]

Hedgehog Signaling as a Therapeutic Target for Airway Remodeling and Inflammation in Allergic Asthma

32 | Nov 10 2022

Anthony Tam et al. found that TGFβ1-induced airway remodeling was partially mediated through the hedgehog signaling pathway via the PTCH1-SMO-GLI axis. [Read the Full Post]

Cardiac Sodium/Hydrogen Exchanger (NHE11) as a Novel Potential Target for SGLT2i in Heart Failure: A Preliminary Study

43 | Oct 28 2022

Lorena Pérez-Carrillo et al. showed alterations in several sodium transports and reinforced the importance of channels in HF progression. [Read the Full Post]

A Protein Kinase D Inhibitor Suppresses AKT on T cells and Antagonizes Cancer Immunotherapy by Anti-PD-1

50 | Oct 26 2022

Kazuhide Miyamoto et al. thought that PKD was fundamentally required for T-cell reactivation by anti-PD-1, therefore inhibition of PKD was not appropriate for combination therapy with anti-PD-1. [Read the Full Post]

Chai-Hu-San-Shen Capsule Ameliorates Ventricular Arrhythmia Through Inhibition of the CaMKII/FKBP12.6/RyR2/Ca2+ Signaling Pathway in Rats with Myocardial Ischemia

46 | Oct 20 2022

Longqing Chen et al. found that CHSSC might reduce the incidence of ventricular arrhythmias following myocardial ischemia through inhibition of the CaMKII/RyR2/FKBP12.6/Ca2+ signaling pathway. [Read the Full Post]

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

39 | Oct 15 2022

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

Identification of solamargine as a cisplatin sensitizer through phenotypical screening in cisplatin-resistant NSCLC organoids

65 | Sep 02 2022

Yi Han et al. found that a new direction for further treatment of advanced DDP-resistant lung cancer patients. [Read the Full Post]

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

60 | Aug 08 2022

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

Giant Basal Cell Carcinoma of the Axilla: 8-year Follow-up of a Case Treated with Excision, Vismodegib, and Radiotherapy

87 | Jul 05 2022

Shih-Chiang Kuo et al. illustrated a rare disease with an 8-year follow-up, involving different therapeutic strategies against multiple recurrences. [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

375 | 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]

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

171 | Jun 07 2022

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

Inside the cracked kernel: establishing the molecular basis of AMG510 and MRTX849 in destabilising KRASG12C mutant switch I and II in cancer treatment

246 | May 14 2022

Abdul Rashid Issahaku et al. found that these insights present useful atomistic perspectives into the success of AMG510 and MRTX849 which could guide the design of more selective and potent KRAS inhibitors.Communicated by Ramaswamy H. Sarma. [Read the Full Post]

Non-cytomembrane PD-L1: An atypical target for cancer

240 | May 12 2022

Honggang Ying et at. highlighted that non-cytomembrane PD-L1s were of significant cancer diagnostic value and were promising therapeutic targets to treat cancer. [Read the Full Post]

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

125 | May 04 2022

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

Treatment patterns, effectiveness, and patient-reported outcomes of palbociclib therapy in Chinese patients with advanced breast cancer: A multicenter ambispective real-world study

134 | Apr 28 2022

Lesang Shen et al. thought that Palbociclib was effective for front-line use and for treating endocrine-sensitive patients in real-world China and was generally well tolerated. [Read the Full Post]

Diet impacts triple-negative breast cancer growth, metastatic potential, chemotherapy responsiveness, and doxorubicin-mediated cardiac dysfunction

272 | Apr 20 2022

Manuel U Ramirez et al. found that the Mediterranean diet might reduce lung metastatic lesions formation and prevent the development of cardiac toxicities. [Read the Full Post]

B7-H4 expression is upregulated by PKCδ activation and contributes to PKCδ-induced cell motility in colorectal cancer

308 | Apr 13 2022

Bin Zhou et al. found that B7-H4 expression was upregulated by STAT3 activation via PKCδ and played roles in PKCδ-induced cancer cell motility and metastasis, suggesting that the PKCδ/STAT3/B7-H4 axis might be a potential therapeutic target for CRC. [Read the Full Post]

Effect of Maternal Docosahexaenoic Acid Supplementation on Very Preterm Infant Growth: Secondary Outcome of a Randomized Clinical Trial

252 | Apr 13 2022

Georgina Angoa et al. showed that DHA positively affected female infants' neonatal weight profile and velocity and negatively affected male infants' weight at 36 weeks' PMA. [Read the Full Post]

The anti-inflammatory agent bindarit attenuates the impairment of neural development through suppression of microglial activation in a neonatal hydrocephalus mouse model

189 | Mar 02 2022

Eri Iwasawa et al. indicated the potential therapeutic use of anti-inflammatory reagents targeting neuroinflammation in the treatment of neonatal hydrocephalus. [Read the Full Post]

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

313 | Feb 05 2022

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

Inhibitor GSK690693 extends Drosophila lifespan via reduce AKT signaling pathway

936 | Jan 27 2022

Xingyi Cheng et al. indicated that GSK690693 might become an effective compound for anti-aging intervention. [Read the Full Post]

The Role of Prostaglandin E1 as a Pain Mediator through Facilitation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 via the EP2 Receptor in Trigeminal Ganglion Neurons of Mice

237 | Jan 26 2022

Jean Kwon et al. discovered that PGE1 played a role in mechanical allodynia through HCN2 channel facilitation via the EP2 receptor in nociceptive neurons. [Read the Full Post]

Probing the multimodal fungiform papilla: complex peripheral nerve endings of chorda tympani taste and mechanosensitive fibers before and after Hedgehog pathway inhibition

205 | Dec 24 2021

Christopher R Donnelly et al. found that the complex, extragemmal nerve endings within and disbursed under the apical FP were the mechanosensitive nerve endings of the CT that remained after HH pathway inhibition. [Read the Full Post]

Evaluation of Hedgehog Pathway Inhibition on Nevoid Basal Cell Carcinoma Syndrome Fibroblasts and Basal Cell Carcinoma-Associated Fibroblasts: Are Vismodegib and Sonidegib Useful to Target Cancer-Prone Fibroblasts

221 | Dec 23 2021

Laura Eibenschutz et al. demonstrated that vismodegib and sonidegib impacting on fibroblast tumour supportive functions might be considered in therapy for BCC independently to the mutation status of Hh components in neoplastic cells. [Read the Full Post]

GLI1-targeting drugs induce replication stress and homologous recombination deficiency and synergize with PARP-targeted therapies in triple negative breast cancer cells

472 | Dec 17 2021

Chinnadurai Mani et al. found that Aberrantly activated GLI1 regulated HR-mediated DNA repair by transcriptionally regulating FANCD2 to overcome chemotherapy-induced replication stress and DNA damage. [Read the Full Post]

Healthcare resource utilization in patients treated with empagliflozin in East Asia

295 | Dec 04 2021

Wayne H-H Sheu et al. found that empagliflozin treatment was associated with lower inpatient care needs and other healthcare resource utilization than DPP-4 inhibitors in routine clinical practice in East Asia in this study. [Read the Full Post]

Evaluation of protein kinase D auto-phosphorylation as biomarker for NLRP3 inflammasome activation

301 | Dec 01 2021

Diane Heiser et al. found thta PKD auto-phosphorylation could be triggered by a broad range of stimuli unrelated to NLRP3 inflammasome assembly. [Read the Full Post]

Cadherin-12 Regulates Neurite Outgrowth Through the PKA/Rac1/Cdc42 Pathway in Cortical Neurons

553 | Nov 26 2021

Beibei Guo et al. reported the effect of CDH12 on axonal extension in vitro and in vivo. [Read the Full Post]

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

389 | Nov 21 2021

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

Discovery of novel quinazoline-based covalent inhibitors of KRAS G12C with various cysteine-targeting warheads as potential anticancer agents

441 | Nov 13 2021

Ling Li et.al suggested that the novel covalent inhibitors of KRAS G12C with different warheads deserve further investigation as potential anticancer agents. [Read the Full Post]

"Petal-like" size-tunable gold wrapped immunoliposome to enhance tumor deep penetration for multimodal guided two-step strategy

355 | Oct 11 2021

Yanan Li et al. provided a synergistic treatment strategy that could broaden the conventional treatment alone. [Read the Full Post]

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

623 | Sep 13 2021

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

Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial

440 | Aug 12 2021

Alexander J Stratigos et al. found that cemiplimab exhibited clinically meaningful antitumour activity and an acceptable safety profile in patients with locally advanced basal cell carcinoma after HHI therapy. [Read the Full Post]

MLN4924 inhibits hedgehog signaling pathway and activates autophagy to alleviate mouse laser-induced choroidal neovascularization lesion

414 | Aug 09 2021

Laiqing Xie et al. found that MLN4924 relieved the formation of mouse laser-induced CNV lesion might via up-regulating hedgehog pathway-regulated autophagy. [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

1233 | 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]

The KRAS G12C Inhibitor MRTX849 Reconditions the Tumor Immune Microenvironment and Sensitizes Tumors to Checkpoint Inhibitor Therapy

639 | Jun 22 2021

David M Briere et al. demonstrated KRAS inhibition reversed an immunosuppressive tumor microenvironment and sensitized tumors to CIT through multiple mechanisms. [Read the Full Post]

Flurbiprofen as a biphenyl scaffold for the design of small molecules binding to PD-L1 protein dimer

795 | Jun 20 2021

Christian Bailly et al. found that the longer FLB derivative HCT1026 appeard as a suitable binder of the PD-L1 dimer, sliding well along the BMS binding cavity. [Read the Full Post]

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

493 | Jun 10 2021

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

β-Sitosterol-D-Glucopyranoside Mimics Estrogenic Properties and Stimulates Glucose Utilization in Skeletal Muscle Cells

387 | Jun 03 2021

Jyotsana Pandey et al. found the estrogenic activity of BSD to stimulate glucose utilization in skeletal muscle cells via PI-3K/AKT-dependent mechanism. [Read the Full Post]

Thyroglobulin as a negative marker for malignancy in canine and human breast tumors

728 | May 19 2021

Sung-Hyun Hwang et al. found that Tg could be a negative indicator of malignancy in canine and human breast neoplasia. [Read the Full Post]

Development and validation of an MRI-based radiomics nomogram for distinguishing Warthin's tumour from pleomorphic adenomas of the parotid gland

689 | May 07 2021

Ying-Mei Zheng et al. found that the MRI-based radiomics nomogram had good performance in distinguishing parotid WT from PMA, which could optimize clinical decision-making. [Read the Full Post]

A fluorometric erythrophagocytosis assay using differentiated monocytic THP-1 cells to assess the clinical significance of antibodies to red blood cells

600 | May 06 2021

Abdelwahab Hassan Ahmed Balola et al. thought that the flow cytometry-based erythrophagocytosis test described here was quantitative, highly reliable, and might be helpful for the assessment of the clinical significance of antibodies to RBCs. [Read the Full Post]

Triple oral combination therapy with macitentan, riociguat, and selexipag for pulmonary arterial hypertension

274 | Mar 17 2021

Mizuki Momoi et al. found that triple oral combination therapy with macitentan, riociguat, and selexipag sufficiently improved clinical parameters and was well tolerated in patients with PAH. [Read the Full Post]

tPA Mobilizes Immune Cells That Exacerbate Hemorrhagic Transformation in Stroke

500 | Mar 14 2021

Kaibin Shi et al. suggested that immune invasion of the neurovascular unit represented a previously unrecognized mechanism underlying tPA-mediated brain hemorrhage, which could be overcome by precise immune modulation during thrombolytic therapy. [Read the Full Post]

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

549 | Feb 12 2021

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

G ATA2 mediates the negative regulation of the prepro-thyrotropin-releasing hormone gene by liganded T3 receptor β2 in the rat hypothalamic paraventricular nucleus

420 | Feb 02 2021

Go Kuroda et al. suggested that GATA2 transactivated the rat prepro-TRH gene and that liganded TRβ2 interfered with this activation via a tethering mechanism as in the case of the TSHβ gene. [Read the Full Post]

Augmenter of Liver Regeneration (ALR) regulates bile acid synthesis and attenuates bile acid-induced apoptosis via glycogen synthase kinase-3β (GSK-3β) inhibition

1335 | Feb 02 2021

Sara Ibrahim et al. thought that rALR might contribute to protecting hepatocytes from toxic concentrations of bile acids by down-regulating their denovo synthesis, attenuating apoptosis by activation of PI3K/Akt - GSK3β pathway and inhibition of JNK signaling. [Read the Full Post]

The Role of Actin in Muscle Spasms in a Case Series of Patients with Advanced Basal Cell Carcinoma Treated with a Hedgehog Pathway Inhibitor

392 | Jan 03 2021

Natalie Teh et al. presented a case series of patients with muscle spasms during treatment with sonidegib and proposed an alternate etiology related to increased actin expression. [Read the Full Post]

A Vismodegib Experience in Elderly Patients with Basal Cell Carcinoma: Case Reports and Review of the Literature

473 | Jan 02 2021

Anna Passarelli et al. reported two case reports of BCC elderly patients in order to demonstrate both efficacy and safety of the Hedgehog inhibitors. [Read the Full Post]

Gli affects the stemness and prognosis of epithelial ovarian cancer via homeobox protein NANOG

572 | Dec 28 2020

Huan Zhao et al. found that Gli and NANOG might be effective indicators of platinum resistance and prognosis in EOC. [Read the Full Post]

Empagliflozin and the Diabetic Kidney: Pathophysiological Concepts and Future Challenges

458 | Dec 16 2020

Georgios S Papaetis discussed the safety of empagliflozin therapy and its future role in order to ameliorate the global burden of CKD both in patients with and without diabetes. [Read the Full Post]

Protein Kinase D1, Reduced in Human Pancreatic Tumors, Increases Secretion of Small Extracellular Vesicles From Cancer Cells That Promote Metastasis to Lung in Mice

424 | Dec 14 2020

Milena Armacki et al. found that human pancreatic ductal adenocarcinoma had reduced levels of PRKD1 compared with nontumor pancreatic tissues. [Read the Full Post]

Scabronine G Methyl Ester Improves Memory-Related Behavior and Enhances Hippocampal Cell Proliferation and Long-Term Potentiation via the BDNF-CREB Pathway in Olfactory Bulbectomized Mice

639 | Dec 08 2020

Osamu Nakagawasai et al. revealed the potential of SG-ME in improving memory impairments by enhancing cell proliferation and LTP via activation of the BDNF/CREB signaling pathway in neurons. [Read the Full Post]

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

499 | Dec 03 2020

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

An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development

732 | Nov 22 2020

Sunita Shankar et al. supported a biphasic model of pancreatic cancer development: an AGO2-independent early phase of PanIN formation reliant on EGFR-RAS signaling, and an AGO2-dependent phase wherein the mutant KRAS-AGO2 interaction was critical for PDAC progression. [Read the Full Post]

Neuroprotective Effects of the Sonic Hedgehog Signaling Pathway in Ischemic Injury through Promotion of Synaptic and Neuronal Health

397 | Oct 13 2020

Sen Yin et al.demonstrated that activation of the Shh signaling pathway played a neuroprotective role in response to ischemic exposure via promotion of synaptic and neuronal health. [Read the Full Post]

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

509 | Aug 31 2020

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

Cohort analysis of safety and efficacy of vismodegib in Italian patients from the Phase II, multicenter STEVIE study

414 | Jul 19 2020

Paolo Bossi et al. showed a safety profile consistent with the whole population; older age did not affect safety or efficacy. [Read the Full Post]

Phosphoproteomics of short-term hedgehog signaling in human medulloblastoma cells

437 | Jul 14 2020

Tamara Scheidt et al. provided evidence that phosphorylation triggered in response to SMO modulation dictated the localization of hedgehog pathway components within the primary cilium and affected the regulation of the SMO-SUFU-GLI axis. [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

1225 | 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]

Staurosporine and NEM Mainly Impair WNK-SPAK/OSR1 Mediated Phosphorylation of KCC2 and NKCC1

1219 | Jun 18 2020

Jinwei Zhang et al. identified phospho-sites that are responsive to staurosporine or NEM application. [Read the Full Post]

NVP-LDE-225 (Erismodegib) Inhibits Epithelial-Mesenchymal Transition and Human Prostate Cancer Stem Cell Growth in NOD/SCID IL2Rγ Null Mice by Regulating Bmi-1 and microRNA-128

694 | Apr 30 2020

R Nanta et al. suggested that inhibition of the Shh signaling pathway could therefore be a novel therapeutic option in treating prostate cancer. [Read the Full Post]

NVP-LDE225, a Potent and Selective SMOOTHENED Antagonist Reduces Melanoma Growth in Vitro and in Vivo

476 | Apr 30 2020

Ahmad Jalili et al. concluded that inhibition of SHH-GLI signaling pathway in human melanoma by the specific smoothened inhibitor NVP-LDE225 could have potential therapeutic application in human melanoma even in the absence of BRAF(V600E) mutation and warrants further investigations. [Read the Full Post]

GANT61 Alleviates Arthritic Symptoms by Targeting Fibroblast-Like Synoviocytes in CIA Rats

459 | Apr 20 2020

Suping Qin et al. indicated the GANT61 inhibit the proliferation of FLS and alleviated the arthritic symptoms in CIA rats, this implied the GANT61 may be recommended as a possible candidate for the therapy of RA. [Read the Full Post]

How Does Empagliflozin Reduce Cardiovascular Mortality? Insights From a Mediation Analysis of the EMPA-REG OUTCOME Trial

569 | Mar 12 2020

Inzucchi SE et al. indicated in this exploratory analysis from the EMPA-REG OUTCOME trial, changes in markers of plasma volume were the most important mediators of the reduction in risk of CV death with empagliflozin versus placebo. [Read the Full Post]

T-cell death-associated gene 8 accelerates atherosclerosis by promoting vascular smooth muscle cell proliferation and migration

651 | Mar 02 2020

Chen LD et al. demonstrated that Tdag8 mediated phenotype transformation, proliferation and migration of VSMCs via the cAMP/PKA signaling pathway, thus partially contributing to atherosclerosis. [Read the Full Post]

Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial

572 | Feb 25 2020

Basset-Séguin N et al. showed the primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control. [Read the Full Post]

One Hundred Faces of Cyclopamine

493 | Dec 15 2019

Iovine V et al. indicated that the aim of the present work is to review the main synthetic strategies to cyclopamine and its derivatives, with particular emphasis on the challenging chemical modifications aimed at improving the biological activity of the molecule. [Read the Full Post]

Pharmacokinetics and Biodistribution of GDC-0449 Loaded Micelles in Normal and Liver Fibrotic Mice

589 | Sep 26 2019

Dutta R et al. showed that M6P-conjugated GDC-0449 loaded mixed micelles may be used as a potential drug delivery vehicle for treating liver fibrosis. [Read the Full Post]

Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling

509 | Sep 23 2019

Huang P et al. proposed that the endogenous Smoothened activator is cholesterol, not oxysterols, and that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol. [Read the Full Post]

Vorapaxar: The Current Role and Future Directions of a Novel Protease-Activated Receptor Antagonist for Risk Reduction in Atherosclerotic Disease

517 | Jul 09 2019

Gryka RJ et al. indicated vorapaxar provides clinicians with a novel mechanism of action to further reduce the burden of ischemic heart disease. Identification of patients with a high ischemic risk and low bleeding risk would enable clinicians to maximize the utility of this unique agent. [Read the Full Post]

Efficacy of Ramelteon for delirium after lung cancer surgery

711 | 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]

Effect of bucladesine, pentoxifylline, and H-89 as cyclic adenosine monophosphate analog, phosphodiesterase, and protein kinase A inhibitor on acute pain

504 | Jun 09 2019

Salehi F et al. indicated PTX, H-89, and Db-cAMP affect the thermal-induced pain by probably interacting with intracellular cAMP and cGMP signaling pathways and cyclic nucleotide-dependent protein kinases. [Read the Full Post]

Is maraviroc useful in multiple sclerosis patients with natalizumab-related progressive multifocal leukoencephalopathy

864 | Apr 15 2019

Scarpazza C et al. showed that maraviroc did not show any clear effect in modulating the clinical course of PML preventing IRIS. Moreover, once PML-IRIS emerged, the clinical stabilization was achieved only with the use of corticosteroids. Thus, the use of maraviroc should be regarded with extreme caution due the potential adverse events associated with its use. [Read the Full Post]

Combining Smoothened Agonist and NEL-Like Protein-1 Enhances Bone Healing

775 | Apr 12 2019

Lee S et al. suggested that combining the hedgehog signaling agonist SAG and NELL-1 has potential as a novel therapeutic strategy for the healing of critical-size bone defects. Future directions will include optimization of dosage and delivery strategy for an SAG and NELL-1 combination product. [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]

The microRNA-7-mediated reduction in EPAC-1 contributes to vascular endothelial permeability and eNOS uncoupling in murine experimental retinopathy

480 | Mar 16 2019

Garcia-Morales V et al. indicated that EPAC-1 resembles an efficacious and druggable target molecule for the amelioration of (diabetic) retinopathy. [Read the Full Post]

Cyclopamine: from cyclops lambs to cancer treatment

614 | Mar 01 2019

Lee ST et al. showed inhibitors of the Hh signaling pathway, including cyclopamine derivatives, have been targeted as potential treatments for certain cancers and other diseases associated with the Hh signaling pathway. [Read the Full Post]

Antiangiogenic Effects of Doxazosin on Experimental Choroidal Neovascularization in Mice

539 | Feb 28 2019

Guo J et al. found that Doxazosin exerts antiangiogenic actions in an experimental mouse model of CNV and may be a potential adjunctive therapy for neovascular age-related macular degeneration in humans. [Read the Full Post]

Nano-emulsions as vehicles for topical delivery of forskolin

597 | Feb 14 2019

Miastkowska M et al. showed that the nano-emulsions developed in this study could be used as effective carriers for topical administration of forskolin. [Read the Full Post]

Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors

1183 | Feb 07 2019

CXCL12 competition binding studies were proven to be highly valuable as an initial screening assay and indicative for the pharmacological and functional profile of competitive CXCR4 antagonists, which will help the design of new potent CXCR4 inhibitors. [Read the Full Post]

Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

0 | Jan 27 2019

Du J et al. suggested SBE as a novel drug candidate for NSCLC which specifically and sensitively targets SHH signaling pathway. [Read the Full Post]

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

1147 | 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]

Glucose Metabolism and AMPK Signaling Regulate Dopaminergic Cell Death Induced by Gene (α-Synuclein)-Environment (Paraquat) Interactions

757 | Jan 16 2019

Anandhan A et al. demonstrated that glucose metabolism and AMPK regulate dopaminergic cell death induced by gene (α-synuclein)-environment (PQ) interactions. [Read the Full Post]

PAFR selectively mediates radioresistance and irradiation-induced autophagy suppression in prostate cancer cells

576 | Jan 07 2019

Yao B et al. elucidated a significant role of GB in selectively improving the outcomes of PCa receiving radiation therapy. [Read the Full Post]

IL27 controls skin tumorigenesis via accumulation of ETAR-positive CD11b cells in the pre-malignant skin

528 | Dec 31 2018

Dibra D et al. indicated that these findings are clinically relevant, as the number of IL27RA-positive cells in the stroma is highly related to tumor de-differentiation in patients with squamous cell carcinomas. [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]

Spinal Glutamate Transporters Are Involved in the Development of Electroacupuncture Tolerance

1133 | Dec 16 2018

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

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

1047 | 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]

Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors

1275 | Dec 07 2018

Dragoj M et al. demonstrated that p53/PTEN deficient NSCLCs have extremely invasive phenotype and provided a rationale for the use of CXCR4 or FAK inhibitors for the suppression of NSCLC dissemination. [Read the Full Post]

Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

765 | Nov 30 2018

Du J et al. suggested SBE as a novel drug candidate for NSCLC which specifically and sensitively targets SHH signaling pathway. [Read the Full Post]

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

945 | 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]

Acquired resistance to combination treatment through loss of synergy with MEK and PI3K inhibitors in colorectal cancer

0 | Oct 14 2018

Bhattacharya B et al. highlight that AQR to combination treatment may develop through alternative mechanisms to those of single agent treatment, including a change in drug interaction. [Read the Full Post]

An RNA interference screen identifies new avenues for nephroprotection

966 | 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

1215 | 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]

SGLT inhibitors attenuate NO-dependent vascular relaxation in the pulmonary artery but not in the coronary artery

853 | Sep 23 2018

Han Y et al. suggested that SGLT inhibitors differentially regulate vascular relaxation depending on the type of arteries, duration of the treatment, and health condition, such as diabetes. [Read the Full Post]

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

1431 | 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]

Upregulation of hydroxysteroid sulfotransferase 2B1b promotes hepatic oval cell proliferation by modulating oxysterol-induced LXR activation in a mouse model of liver injury

940 | Sep 14 2018

Wang Z et al. indicated that upregulation of SULT2B1b might promote HOC proliferation and aggravate liver injury via the suppression of oxysterol-induced LXR activation in chemically induced mouse liver injury. [Read the Full Post]

Boosting Endogenous Resistance of Brain to Ischemia

1067 | 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]

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

1451 | 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]

Upregulation of programmed cell death ligand 1 promotes resistance response in non-small-cell lung cancer patients treated with neo-adjuvant chemotherapy

2480 | Aug 26 2018

Zhang P et al. suggested that the upregulation of PD-L1 promotes a resistance response in lung cancer cells that might be through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway and suppression of tumor-infiltrating lymphocytes. The high expression of PD-L1 after NAC could be an indication of therapeutic resistance and poor prognosis in patients with non-small-cell lung cancer. [Read the Full Post]

The diabetes medication Canagliflozin reduces cancer cell proliferation by inhibiting mitochondrial complex-I supported respiration

851 | Aug 26 2018

Villani LA et al. indicated that like the biguanide metformin, Canagliflozin not only lowers blood glucose but also inhibits complex-I supported respiration and cellular proliferation in prostate and lung cancer cells. These observations support the initiation of studies evaluating the clinical efficacy of Canagliflozin on limiting tumorigenesis in pre-clinical animal models as well epidemiological studies on cancer incidence relative to other glucose lowering therapies in clinical populations. [Read the Full Post]

Central Agonism of GPR120 Acutely Inhibits Food Intake and Food Reward and Chronically Suppresses Anxiety-Like Behavior in Mice

881 | Aug 23 2018

Auguste S et al. suggested that GPR120 could mediate the effects of central ω-3 polyunsaturated fatty acids to inhibit appetite. The anxiolytic effect elicited by GPR120 agonist infusions favors the testing of compounds that can enter the brain to activate GPR120 for the mitigation of anxiety. [Read the Full Post]

CRISPR/Cas-Mediated Knockin in Human Pluripotent Stem Cells

1331 | 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]

Cross-talk between Notch and Hedgehog regulates hepatic stellate cell fate in mice

1147 | Jul 14 2018

Xie G, et al. found that the Notch and Hedgehog pathways interact to control the fate of key cell types involved in adult liver repair by modulating epithelial-to-mesenchymal-like/mesenchymal-to-epithelial-like transitions. [Read the Full Post]

AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo

3447 | Jun 20 2018

Xi Y et al. supported the progression of this molecule into future evaluation as a valuable anti-gastric cancer candidate. [Read the Full Post]

Both genetic deletion and pharmacological blockade of lysophosphatidic acid LPA1 receptor results in increased alcohol consumption

758 | Jun 17 2018

Castilla-Ortega E et al. suggested a relevant role for the LPA/LPA1 signaling system in alcoholism. In addition, the LPA1-null mice emerge as a new model for genetic vulnerability to excessive alcohol drinking. The pharmacological manipulation of LPA1 receptor arises as a new target for the study and treatment of alcoholism. [Read the Full Post]

Lysophosphatidic acid upregulates connective tissue growth factor expression in osteoblasts through the GPCR/PKC and PKA pathways

971 | Jun 17 2018

Yu ZL et al. indicated that LPA increases CCN2 expression through the activation of PKC and PKA. Thus, the regulatory functions of the PKC and PKA pathways are implicated in the LPA-induced increase in CCN2 expression. [Read the Full Post]

Targeting colorectal cancer cells by a novel sphingosine kinase 1 inhibitor PF-543

749 | Jun 06 2018

Ju T et al. found that mitochondrial programmed necrosis pathway is likely the key mechanism responsible for PF-543's actions in CRC cells. [Read the Full Post]

Unique roles of Akt1 and Akt2 in IGF-IR mediated lung tumorigenesis

1812 | May 21 2018

Franks SE et al. suggested that compounds selectively targeting AKT1 may prove more effective than compounds that inhibit all three AKT isoforms at least in the treatment of lung adenocarcinoma. [Read the Full Post]

PI3Kα isoform-dependent activation of RhoA regulates Wnt5a-induced osteosarcoma cell migration

6157 | May 20 2018

Zhang A et al. demonstrated that RhoA acts as the downstream of PI3K/Akt signaling (specific PI3Kα, Akt1 and Akt2 isoforms) and mediated Wnt5a-induced the migration of osteosarcoma cells. [Read the Full Post]

Gli1-Mediated Regulation of Sox2 Facilitates Self-Renewal of Stem-Like Cells and Confers Resistance to EGFR Inhibitors in Non-Small Cell Lung Cancer

1090 | May 18 2018

Bora-Singhal N et al. demonstrated a cooperative functioning of the EGFR signaling and Hedgehog pathways in governing the stem-like functions of NSCLC cancer stem cells and presents a novel therapeutic strategy to combat NSCLC harboring EGFR mutations. [Read the Full Post]

Stimulation of Transforming Growth Factor-β1-Induced Endothelial-To-Mesenchymal Transition and Tissue Fibrosis by Endothelin-1 (ET-1): A Novel Profibrotic Effect of ET-1

725 | May 12 2018

Wermuth PJ et al. suggested a novel role for ET-1 in the establishment and progression of tissue fibrosis. [Read the Full Post]

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

1136 | 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]

Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism

980 | Apr 27 2018

Wu YM et al. found that PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta. [Read the Full Post]

Modulation of Nav1.8 by Lysophosphatidic Acid in the Induction of Bone Cancer Pain

802 | Apr 26 2018

Pan HL et al. demonstrated the modulation of Nav1.8 by LPA in DRG neurons, and that this probably underlies the peripheral mechanism by which bone cancer pain is induced. [Read the Full Post]

Suppression of chronic lymphocytic leukemia progression by CXCR4 inhibitor WZ811

1742 | Apr 25 2018

Li SH et al. demonstrated that WZ811 may be a novel approach in the treatment of chronic lymphocytic leukemia. [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

1374 | 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]

Critical role of CXCL4 in the lung pathogenesis of influenza (H1N1) respiratory infection

1802 | Apr 02 2018

Guo L et al. identified CXCL4 as a vital immunoregulatory chemokine essential for protecting mice against influenza A virus infection, especially as it affects the development of lung injury and neutrophil mobilization to the inflamed lung. [Read the Full Post]

Adiponectin promotes human jaw bone marrow mesenchymal stem cell chemotaxis via CXCL1 and CXCL8

0 | Apr 01 2018

Pu Y et al. supported the above results. Our data suggest that APN can promote h-JBMMSC chemotaxis by up-regulating CXCL1 and CXCL8. [Read the Full Post]

A Novel TGR5 Activator WB403 Promotes GLP-1 Secretion and Preserves Pancreatic β-Cells in Type 2 Diabetic Mice

1139 | Mar 30 2018

Zheng C et al. demonstrated that TGR5 activator WB403 effectively promoted GLP-1 release, improved hyperglycemia and preserved the mass and function of pancreatic β-cells, whereas it did not show a significant side effect on gallbladder. [Read the Full Post]

Mutant p53 in concert with an interleukin-27 receptor alpha deficiency causes spontaneous liver inflammation, fibrosis, and steatosis in mice

0 | Mar 21 2018

Dibra D et al. found that he combination of mutant p53 and IL27RA(-/-) causes spontaneous liver inflammation, steatosis, and fibrosis in vivo, whereas either gene alone in vivo has no effects on the liver. [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]

Aberrant activation of hedgehog signaling promotes cell proliferation via the transcriptional activation of forkhead Box M1 in colorectal cancer cells

1246 | Mar 13 2018

Wang D et al. indicated the dysregulation of the Hh-Gli1-FoxM1 axis is essential for the proliferation and growth of human CRC cells and offers a potent target for therapeutic intervention in CRC. [Read the Full Post]

Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway

1188 | Mar 12 2018

Zhou F et al. uncovered one of the mechanisms by which Nek2A acts as a modulator of the Hh signaling pathway in the context of a novel negative-feedback loop, which may offer new insights into Gli-mediated Hh signaling regulation in development and human diseases. [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]

PI-3K Inhibitors Preferentially Target CD15+ Cancer Stem Cell Population in SHH Driven Medulloblastoma

1145 | Feb 28 2018

Singh AR, et al. suggested a sequential combination of PI-3K inhibitors and chemotherapy will have augmented efficacy in the treatment of this disease. [Read the Full Post]

Difference in the Pharmacokinetics and Hepatic Metabolism of Antidiabetic Drugs in Zucker Diabetic Fatty and Sprague-Dawley Rats.

1036 | Feb 10 2018

Zhou X, et al. revealed that the activity for CYP3A and UGT was decreased in ZDF rats using the probe substrates, and decreased unbound intrinsic clearance in vitro for glibenclamide, canagliflozin, and troglitazone was consistent with lower plasma clearance in vivo. [Read the Full Post]

CXCL2/MIF-CXCR2 signaling promotes the recruitment of myeloid-derived suppressor cells and is correlated with prognosis in bladder cancer

1917 | Jan 25 2018

Zhang H et al. identified the CXCL2/MIF-CXCR2 axis as an important mediator in MDSC recruitment and as predictors and potential therapeutic targets in BC patients. [Read the Full Post]

mTORC2 mediates CXCL12-induced angiogenesis

2048 | Jan 07 2018

Ziegler ME et al. identified mTORC2 as a critical signaling nexus downstream of CXCL12/CXCR4 that represents a potential link between mTORC2, metabolic regulation, and angiogenesis. [Read the Full Post]

High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker

1033 | Dec 28 2017

Choi HY et al. demonstrated that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission [Read the Full Post]

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

1676 | 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.

1495 | 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]

Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells

1424 | Nov 25 2017

Sun M et al. suggested that NC may be a potential anticancer agent for breast cancer. [Read the Full Post]

Sphingosine kinase inhibition ameliorates chronic hypoperfusion-induced white matter lesions

969 | Nov 10 2017

Yang Y et al. suggested a mechanism for hypoperfusion-associated WML involving HIF-1α-SphK2-S1P-mediated disruption of OPC differentiation, and proposes the SphK signaling pathway as a potential therapeutic target for white matter disease. [Read the Full Post]

Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-β pathways

1657 | Oct 28 2017

Liu J et al. found that CAF-secreted CCL2, CCL5, CCL7 and CXCL16 promote HCC metastasis through the coordinate activation of Hh and TGF-β pathways in HCC cells. [Read the Full Post]

Cytokine correlation analysis based on drug perturbation

3733 | Oct 17 2017

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy. [Read the Full Post]

Cannabinoid receptor-2 stimulation suppresses neuroinflammation by regulating microglial M1/M2 polarization through the cAMP/PKA pathway in an experimental GMH rat model.

0 | Oct 06 2017

Tao Y et al. proposed that promotion of microglial M2 polarization through the cAMP/PKA pathway participates in the CB2R-mediated anti-inflammatory effects after GMH induction. [Read the Full Post]

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

2423 | 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]

Overexpression of cannabinoid receptor 1 promotes renal cell carcinoma progression

1196 | 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

1322 | 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

1617 | 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

2509 | 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

1939 | 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]

Niacin receptor GPR109A inhibits insulin secretion and is down-regulated in type 2 diabetic islet beta-cells

1837 | Aug 07 2017

Wang N et al. demonstrated that GPR109A is functionally expressed in both human and murine islet beta-cells. However, the role of GPR109A in the prevention of diabetes or insulinoma needs further study. [Read the Full Post]

Glucose Metabolism and AMPK Signaling Regulate Dopaminergic Cell Death Induced by Gene (α-Synuclein)-Environment (Paraquat) Interactions

1410 | Jun 30 2017

Anandhan A et al. demonstrated that glucose metabolism and AMPK regulate dopaminergic cell death induced by gene (α-synuclein)-environment (PQ) interactions. [Read the Full Post]

Structural basis of Smoothened regulation by its extracellular domains

1806 | Jun 22 2017

Byrne EF et al. clarified the structural mechanism by which the activity of a GPCR is controlled by ligand-regulated interactions between its extracellular and transmembrane domains. [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]

GLI inhibitor GANT61 kills melanoma cells and acts in synergy with obatoclax

0 | May 05 2017

Vlčková K et al. found that GANT61 treatment might become a hopeful and effective anti-melanoma targeted therapy, especially when combined with the BCL2 family inhibitor obatoclax. [Read the Full Post]

GLI inhibitor GANT61 kills melanoma cells and acts in synergy with obatoclax

1772 | Apr 27 2017

Vlčková K et al. found that GANT61 treatment might become a hopeful and effective anti-melanoma targeted therapy, especially when combined with the BCL2 family inhibitor obatoclax. [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]

Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells

0 | Apr 12 2017

Fu J et al disclosed novel signaling cascades of macrophage-mediated bilateral bystander responses that the release of TNF-α and IL-8 regulated by MAPK and NF-κB pathways synergistically increased cellular injury after α-particle irradiation. [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]

Beneficial metabolic actions of a stable GIP agonist following pretreatment with a SGLT2 inhibitor in high fat fed diabetic mice

1486 | Mar 26 2017

Millar PJ et al demonstratd that (DAla(2))GIP can exert beneficial metabolic control in high fat fed diabetic mice pre-treated with DAPA. The results highlight possibility of a targeted and personalized approach using a GIP agonist and SGLT2 inhibitor for the treatment of type 2 diabetes. [Read the Full Post]

Inhibition of Human UDP-Glucuronosyltransferase Enzymes by Canagliflozin and Dapagliflozin: Implications for Drug-Drug Interactions

3 | Mar 26 2017

Pattanawongsa A et al found that since the sodium-glucose cotransporter 2 inhibitors share common structural features, notably a glycoside moiety, investigation of drugs in this class for effects on UGT to identify (or exclude) potential drug-drug interactions is warranted. [Read the Full Post]

IgG subclasses determine pathways of anaphylaxis in mice

3116 | 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

2438 | 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]

Mutant p53 in concert with an interleukin-27 receptor alpha deficiency causes spontaneous liver inflammation, fibrosis, and steatosis in mice

1449 | Feb 22 2017

The combination of mutant p53 and IL27RA(-/-) causes spontaneous liver inflammation, steatosis, and fibrosis in vivo, whereas either gene alone in vivo has no effects on the liver. [Read the Full Post]

SMO Gene Amplification and Activation of the Hedgehog Pathway as Novel Mechanisms of Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Lung Cancer

1863 | Feb 21 2017

Della Corte CM, et al.'s result supports the role of the Hh pathway in mediating resistance to anti-EGFR-TKIs through the induction of EMT and suggests new opportunities to design new treatment strategies in lung cancer. [Read the Full Post]

Targeting hedgehog signaling reduces self-renewal in embryonal rhabdomyosarcoma

0 | Feb 20 2017

Satheesha S, et al.‘s ’ work identifies novel functional aspects of hedgehog signaling in ERMS, redefines the rationale for its targeting as means to control ERMS self-renewal and underscores the importance of studying functional tumor heterogeneity in pediatric cancers. [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]

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma

0 | Feb 19 2017

Brun SN, et al.'s studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease. [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

2378 | 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]

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

3210 | 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

1910 | 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

1964 | 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]

Inhibition of Human UDP-Glucuronosyltransferase Enzymes by Canagliflozin and Dapagliflozin: Implications for Drug-Drug Interactions

1792 | Jan 29 2017

Pattanawongsa A et al. reported the inhibition of human recombinant UGTs by CNF and DPF, along with the Ki values for selected recombinant and human liver microsomal UGTs. [Read the Full Post]

SMO Gene Amplification and Activation of the Hedgehog Pathway as Novel Mechanisms of Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Lung Cancer

1400 | Jan 11 2017

Della Corte CM et al. found that the role of the Hh pathway in mediating resistance to anti-EGFR-TKIs through the induction of EMT and suggests new opportunities to design new treatment strategies in lung cancer. [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

4432 | 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]

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma

1758 | Jan 09 2017

Brun SN, et al.'s studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease. [Read the Full Post]

Targeting hedgehog signaling reduces self-renewal in embryonal rhabdomyosarcoma

1839 | Jan 09 2017

Satheesha S, et al.'s work identifies novel functional aspects of hedgehog signaling in ERMS, redefines the rationale for its targeting as means to control ERMS self-renewal and underscores the importance of studying functional tumor heterogeneity in pediatric cancers. [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

2236 | 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]

Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells

1722 | Dec 09 2016

The study of Sun M et al. suggested that NC may be a potential anticancer agent for breast cancer. [Read the Full Post]

Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-β pathways

5352 | Nov 10 2016

Liu J et al. found thatCAF-secreted CCL2, CCL5, CCL7 and CXCL16 promote HCC metastasis through the coordinate activation of Hh and TGF-β pathways in HCC cells. [Read the Full Post]

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

4278 | Nov 03 2016

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

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

1557 | Sep 20 2016

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

2130 | 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]

Beneficial metabolic actions of a stable GIP agonist following pre-treatment with a SGLT2 inhibitor in high fat fed diabetic mice

1734 | Sep 05 2016

Millar PJ, et al. demonstrated possibility of a targeted and personalized approach using a GIP agonist and SGLT2 inhibitor for the treatment of type 2 diabetes. [Read the Full Post]

PET imaging for chemokine receptor-4 detection in multiple myeloma

4777 | Mar 10 2015

Philipp-Abbrederis et al. developed a novel CXCR4 probe [68Ga]Pentixafor for mapping of CXCR4 expression density in vivo. [Read the Full Post]

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

15343 | Jan 23 2015

Dubrovsky et al. developed an antibody, ESKM, which is therapeutically effective on acute and chronic leukemias in murine models. [Read the Full Post]

The inhibitor of CCR5 block metastasis of v-Src oncogene-transformed prostate cancer

3640 | Dec 11 2014

Sicoli et al. identified CCR5 signaling activation is important for v-Src oncogene-transformed prostate cancer metastasis, and it antagonist can attenuate the burden. [Read the Full Post]

Maraviroc is an antiretroviral drug in the CCR5 receptor antagonist class

3649 | Mar 13 2014

Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM, respectively. [Read the Full Post]

FTY720 is a first in class orally bioavailable

2741 | Feb 24 2014

The inhibitory effect of S1P is revered by various concentrations of FTY720. [Read the Full Post]

TAK 875 was dissolved in dimethyl sulfoxide

2976 | Feb 12 2014

AK-875 is a selective GPR40 agonist with EC50 of 14 nM, 400-fold more potent than oleic acid. [Read the Full Post]

Maraviroc is an antiretroviral drug in the CCR5

0 | Jan 21 2014

Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM, respectively. [Read the Full Post]

Maraviroc is an antiretroviral drug in the CCR5 receptor

3694 | Dec 29 2013

Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM, respectively. [Read the Full Post]

Dapagliflozin is a drug used to treat type 2 diabetes

0 | Dec 20 2013

Dapagliflozin is 32-fold more potent than phlorizin against hSGLT2 but 4-fold less than phlorizin against hSGLT1. [Read the Full Post]

Dapagliflozin is a drug used to treat type 2 diabetes

2779 | Nov 27 2013

Dapagliflozin is not sensitive to hSGLT1 with a 1200-fold IC50. [Read the Full Post]

Maraviroc is an antiretroviral drug in the CCR5

3724 | Nov 20 2013

Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM, respectively. [Read the Full Post]

FTY720 is a first in class orally bioavailable compound

2654 | Nov 05 2013

The inhibitory effect of S1P is revered by various concentrations of FTY720, with IC50 effect of 173 nM. [Read the Full Post]

FTY720 is phosphorylated by sphingosine kinase type 2

2962 | Sep 30 2013

The inhibitory effect of S1P is revered by various concentrations of FTY720, with IC50 effect of 173 nM. [Read the Full Post]

NPS2143 is a novel potent and selective antagonist of Ca

2877 | Sep 10 2013

n rats, NPS 2143 results in a rapid 4- to 5-fold increase in plasma PTH levels and also a transient increase in plasma Ca2+ levels. [Read the Full Post]

MRS2578 is a selective antagonist of P2Y6 nucleotide receptors

3133 | Jul 29 2013

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

Vicriviroci s a pyrimidine CCR5 entry inhibitor of HIV1

3681 | Jul 20 2013

Vicriviroc binds with higher affinity to CCR5 versus SCH-C (SCH-351125) in competition binding assays with Ki value of 0.8 nM versus 2.6 nM. [Read the Full Post]

FTY720 is an immunomodulating drug, approved for treating multiple sclerosis

3273 | Jun 03 2013

Fingolimod is a sphingosine 1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction. [Read the Full Post]

Erismodegib is an orally bioavailable small molecule

3357 | Jan 07 2013

C Kit is a transmembrane receptor tyrosine kinase that binds stem cell factor SCF . CKit is encoded by the kit proto oncogene, localized to human chromosome and to mouse chromosome The c Kit SCF erismodegib interaction is critical for the survival and development of stem cells involved in hematopoiesis [Read the Full Post]

Sorafenib Tosylate is a multikinase inhibitor

2954 | Dec 13 2012

Sorafenib acute HCV infection leads to chronic infection in approximately 80% of cases. Chronic HCV infection is responsible for chronic hepatitis,which is complicated by cirrhosis in approximately 20% of cases. [Read the Full Post]

Maraviroc provide a mechanism to adjust the properties

3639 | Nov 28 2012

Our data also indicate that activity of AurA IFT88 localization affected during disassembly and suggest the integrity of t the Maraviroc is important for the process of removing animals, as in Chlamydomonas. [Read the Full Post]

FTY720 – THE IMMUNE CELLS CONTROLLER

3107 | Apr 11 2012

FTY720: One of the extensively used immunoregulatory drug is Fingolimod, FTY720 is the code for this drug and it is a product of Novartis. The properties like anti-tumor actions and immunosuppressant activities made FTY720 Fingolimod a new hope against the debilitating diseases such as Multiple Sclerosis. FTY720 price for 100mg is around $40. Like many other compounds it is not soluble in water but a reasonable solubility of concentration of 100mg/ml can be attained using organic solvents such as DMSO and ethanol. Structurally FTY720 is an analogue of sphingosine molecule due to which this molecule has the capability to act on sphingosine-1-phosphate receptor, this report has been confirmed by gene deletion and reverse pharmacology studies. Various chemical modifications have been made with FTY720 in order to enhance its efficiency and to take it in clinical trials based on different diseases. If anyone wants to purchase FTY720 for laboratory and clinical uses one can order FTY720 to any FTY720 suppliers. IC50 of this drug is about 0.13 nM. [Read the Full Post]

The regulation of sphingosine-1-phosphate metabolism

4405 | Oct 20 2011

Sphingosine-1-phosphate (S1P) is a signaling sphingolipid and is also referred to as a bioactive lipid mediator. Functions of S1P are mediated by its binding to a class of G-protein coupled receptors of the S1P and Lysophospholipid (LPA) receptor families, and regulate a variety of cell signaling pathways, including cell growth, differentiation, survival, and apoptosis. Many factors in the metabolism pathway of S1P have been considered as potential targets for therapeutic intervention, including the inhibition of S1P activation of the G-protein coupled receptors. [Read the Full Post]

Brinkmann, V. (2007). "Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology." Pharmacol Ther 115(1): 84-105.

3610 | Jul 22 2011

This article reviews S1P receptor subtypes and associated signaling pathways. The relationship between S1P receptors and different diseases is proved in the article. [Read the Full Post]

Rosen, H., P. J. Gonzalez-Cabrera, et al. (2009). "Sphingosine 1-phosphate receptor signaling." Annu Rev Biochem 78: 743-768.

3574 | Jun 10 2011

This review gives us the detail information about S1P receptors from different aspects including subtypes and Genetic Relationships, coupling Promiscuity and Its Consequences, design Features of the S1P Ligand System, S1P Receptor Signaling in Health and Disease and son on. [Read the Full Post]

Nelson, J., A. Bagnato, et al. (2003). "The endothelin axis: emerging role in cancer." Nat Rev Cancer 3(2): 110-116.

3336 | Mar 17 2011

The place of ET-receptor antagonists in cancer therapy for a range of malignancies merits further investigation. [Read the Full Post]