40,751 results match your criteria transient receptor

Investigation of protein-ligand complexes by ligand-based NMR methods.

Carbohydr Res 2021 Apr 9;503:108313. Epub 2021 Apr 9.

Dipartimento di Scienze Chimiche, Complesso Universitario Monte Sant'Angelo, Università di Napoli Federico II, Via Cintia 4, I-80126, Napoli, Italy; CNR, Institute for Polymers, Composites and Biomaterials, IPCB ss, Catania, Italy. Electronic address:

Molecular recognition is at the base of all biological events and its knowledge at atomic level is pivotal in the development of new drug design approaches. NMR spectroscopy is one of the most widely used technique to detect and characterize transient ligand-receptor interactions in solution. In particular, ligand-based NMR approaches, including NOE-based NMR techniques, diffusion experiments and relaxation methods, are excellent tools to investigate how ligands interact with their receptors. Read More

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Modulation of autophagy and transient receptor potential vanilloid 4 channels by montelukast in a rat model of hemorrhagic cystitis.

Life Sci 2021 Apr 14:119507. Epub 2021 Apr 14.

Histology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.

Aims: Hemorrhagic cystitis (HC) is a major urotoxic complication of cyclophosphamide (CPA) therapy. This study investigated the uroprotective effect of montelukast on CPA-induced HC, compared to the efficacy of 2-mercaptoethane sulfonate sodium (MESNA).

Main Methods: Male albino rats were pretreated with MESNA (40 mg/kg/day, IP) or montelukast (10 mg/kg/day, orally) for three days then received a single dose of CPA (200 mg/kg, IP), 1 h after the last dose, and compared to CPA-treated rats receiving drug vehicle. Read More

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Upregulated SOCC and IP3R calcium channels and subsequent elevated cytoplasmic calcium signaling promote nonalcoholic fatty liver disease by inhibiting autophagy.

Mol Cell Biochem 2021 Apr 17. Epub 2021 Apr 17.

Department of General Practice, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China.

Nonalcoholic fatty liver disease (NAFLD) is related to elevated cytoplasmic calcium signaling in hepatocytes, which may be mediated by store-operated calcium channel (SOCC) and inositol triphosphate receptor (IP3R). However, the regulatory effect of calcium signaling on lipid accumulation and degeneration in hepatocytes and the underlying molecular mechanism remain unknown. Autophagy inhibition promotes lipid accumulation and steatosis in hepatocytes. Read More

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Genome-wide gene-diet interaction analysis in the UK Biobank identifies novel effects on Hemoglobin A1c.

Hum Mol Genet 2021 Apr 16. Epub 2021 Apr 16.

Programs in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.

Diet is a significant modifiable risk factor for type 2 diabetes (T2D), and its effect on disease risk is under partial genetic control. Identification of specific gene-diet interactions (GDIs) influencing risk biomarkers such as glycated hemoglobin (HbA1c) is a critical step towards precision nutrition for T2D prevention, but progress has been slow due to limitations in sample size and accuracy of dietary exposure measurement. We leveraged the large UK Biobank (UKB) cohort and a diverse group of dietary exposures, including 30 individual dietary traits and 8 empirical dietary patterns, to conduct genome-wide interaction studies in ~ 340 000 European-ancestry participants to identify novel GDIs influencing HbA1c. Read More

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Rearing temperature conditions (constant vs. thermocycle) affect daily rhythms of thermal tolerance and sensing in zebrafish.

J Therm Biol 2021 Apr 18;97:102880. Epub 2021 Feb 18.

Department of Physiology, Faculty of Biology, University of Murcia, 30100, Murcia, Spain. Electronic address:

In the wild, the environment does not remain constant, but periodically oscillates so that temperature rises in the daytime and drops at night, which generates a daily thermocycle. The effects of thermocycles on thermal tolerance have been previously described in fish. However, the impact of thermocycles on daytime-dependent thermal responses and daily rhythms of temperature tolerance and sensing expression mechanisms remain poorly understood. Read More

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The effects of ACE2 expression mediating pharmacotherapy in COVID-19 patients.

Neth Heart J 2021 Apr 16. Epub 2021 Apr 16.

Department of Experimental Cardiology, Amsterdam University Medical Center, Amsterdam, The Netherlands.

Background: There has been debate on the use of angiotensin-converting enzyme‑2 (ACE2) expression mediating pharmacotherapy in COVID-19 infected patients. Although it has been suggested that these drugs might lead to a higher susceptibility and severity of COVID-19 infection, experimental data suggest these agents may reduce acute lung injury via blocking angiotensin-II-mediated pulmonary permeability, inflammation and fibrosis.

Methods: A systematic literature search was performed to answer the question: What is the effect of medications that influence ACE2 expression (ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), nonsteroidal anti-inflammatory drugs (NSAIDs) and thiazolidinediones) on the outcomes of COVID-19? Relevant outcome measures were mortality (crucial), hospital admission, length of stay, thromboembolic complications (pulmonary embolism, stroke, transient ischaemic attack), need for mechanical ventilation, acute kidney injury and use of renal replacement therapy. Read More

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Transient Stimulation with Psychoplastogens Is Sufficient to Initiate Neuronal Growth.

ACS Pharmacol Transl Sci 2021 Apr 11;4(2):452-460. Epub 2020 Sep 11.

Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California, Davis 95616, United States.

Cortical neuron atrophy is a hallmark of depression and includes neurite retraction, dendritic spine loss, and decreased synaptic density. Psychoplastogens, small molecules capable of rapidly promoting cortical neuron growth, have been hypothesized to produce long-lasting positive effects on behavior by rectifying these deleterious structural and functional changes. Here we demonstrate that ketamine and LSD, psychoplastogens from two structurally distinct chemical classes, promote sustained growth of cortical neurons after only short periods of stimulation. Read More

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Effects of Resmetirom on Noninvasive Endpoints in a 36-Week Phase 2 Active Treatment Extension Study in Patients With NASH.

Hepatol Commun 2021 Apr 4;5(4):573-588. Epub 2021 Jan 4.

Arizona Liver Health Phoenix AZ USA.

Resmetirom (MGL-3196), a selective thyroid hormone receptor-β agonist, was evaluated in a 36-week paired liver biopsy study (NCT02912260) in adults with biopsy-confirmed nonalcoholic steatohepatitis (NASH). The primary endpoint was relative liver fat reduction as assessed by MRI-proton density fat fraction (MRI-PDFF), and secondary endpoints included histopathology. Subsequently, a 36-week active treatment open-label extension (OLE) study was conducted in 31 consenting patients (including 14 former placebo patients) with persistently mild to markedly elevated liver enzymes at the end of the main study. Read More

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Discovery of a Highly Selective and Potent TRPC3 Inhibitor with High Metabolic Stability and Low Toxicity.

ACS Med Chem Lett 2021 Apr 5;12(4):572-578. Epub 2021 Mar 5.

Department of Pharmaceutical Sciences, College of Pharmacy, the University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States.

The overactivation of transient receptor potential canonical 3 (TRPC3) is associated with neurodegenerative diseases and hypertension. Pyrazole 3 (Pyr3) is reported as the most selective TRPC3 inhibitor, but it has two inherent structural limitations: (1) the labile ester moiety leads to its rapid hydrolysis to the inactive Pyr8 , and (2) the alkylating trichloroacrylic amide moiety is known to be toxic. To circumvent these limitations, we designed a series of conformationally restricted Pyr3 analogues and reported that compound maintains high potency and selectivity for human TRPC3 over its closely related TRP channels. Read More

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Residual Viremia Is Linked to a Specific Immune Activation Profile in HIV-1-Infected Adults Under Efficient Antiretroviral Therapy.

Front Immunol 2021 30;12:663843. Epub 2021 Mar 30.

Institute for Human Genetics, CNRS, Montpellier, France.

Chronic immune activation persists in persons living with HIV-1 even though they are aviremic under antiretroviral therapy, and fuels comorbidities. In previous studies, we have revealed that virologic responders present distinct profiles of immune activation, and that one of these profiles is related to microbial translocation. In the present work, we tested in 140 HIV-1-infected adults under efficient treatment for a mean duration of eight years whether low-level viremia might be another cause of immune activation. Read More

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A combination of surgery, theranostics, and liquid biopsy - a personalised oncologic approach to treatment of patients with advanced metastatic neuroendocrine neoplasms.

Int J Med Sci 2021 19;18(10):2166-2175. Epub 2021 Mar 19.

CURANOSTICUM Wiesbaden-Frankfurt at DKD Helios Klinik, Wiesbaden, Germany.

Neuroendocrine neoplasia (NEN) of small bowel (SBNEN) frequently present with metastatic disease. Theranostics (molecular imaging followed by targeting therapy) allow for personalised medicine. Liquid biopsies enable precise identification of residual disease and real-time monitoring of therapeutic response. Read More

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Serotonin-induced vascular permeability is mediated by transient receptor potential vanilloid 4 in the airways and upper gastrointestinal tract of mice.

Lab Invest 2021 Apr 15. Epub 2021 Apr 15.

School of Medical Sciences and Health Innovations Research Institute, RMIT University, Bundoora, VIC, Australia.

Endothelial and epithelial cells form physical barriers that modulate the exchange of fluid and molecules. The integrity of these barriers can be influenced by signaling through G protein-coupled receptors (GPCRs) and ion channels. Serotonin (5-HT) is an important vasoactive mediator of tissue edema and inflammation. Read More

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mRNA therapeutics in cancer immunotherapy.

Mol Cancer 2021 Apr 15;20(1):69. Epub 2021 Apr 15.

BioNTech SE, An der Goldgrube 12, 55131, Mainz, Germany.

Synthetic mRNA provides a template for the synthesis of any given protein, protein fragment or peptide and lends itself to a broad range of pharmaceutical applications, including different modalities of cancer immunotherapy. With the ease of rapid, large scale Good Manufacturing Practice-grade mRNA production, mRNA is ideally poised not only for off-the shelf cancer vaccines but also for personalized neoantigen vaccination. The ability to stimulate pattern recognition receptors and thus an anti-viral type of innate immune response equips mRNA-based vaccines with inherent adjuvanticity. Read More

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Local Anesthetics Inhibit Transient Receptor Potential Vanilloid Subtype 3 Channel Function in Xenopus Oocytes.

Anesth Analg 2021 Apr 15. Epub 2021 Apr 15.

From the Department of Anesthesiology, School of Medicine.

Background: The transient receptor potential vanilloid subtype 3 (TRPV3) channel is activated by innocuous temperature and several chemical stimuli. It is proposed to be involved in pathological pain development and is therefore considered a potential target for treating pain. Local anesthetics have been used for patients with both acute and chronic pain. Read More

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Striatal TRPV1 activation by acetaminophen ameliorates dopamine D2 receptor antagonists-induced orofacial dyskinesia.

JCI Insight 2021 Apr 15. Epub 2021 Apr 15.

Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.

Antipsychotics often cause tardive dyskinesia, an adverse symptom of involuntary hyperkinetic movements. Analysis of the U.S. Read More

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Eltrombopag in children with severe aplastic anemia.

Pediatr Blood Cancer 2021 Apr 15:e29066. Epub 2021 Apr 15.

Department of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Background: Immunosuppressive therapy with horse antithymocyte globulin and cyclosporine currently remains the standard therapy for children with severe aplastic anemia (SAA) who lack human leukocyte antigen (HLA)-identical sibling. The thrombopoietin receptor agonist eltrombopag has been recently approved for SAA patients 2 years and older. However, there are limited data on its safety and efficacy in pediatric cohorts. Read More

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Identification and functional analysis of a biflavone as a novel inhibitor of transient receptor potential vanilloid 4-dependent atherogenic processes.

Sci Rep 2021 Apr 14;11(1):8173. Epub 2021 Apr 14.

Department of Nutrition and Food Science, University of Maryland, College Park, MD, 20742, USA.

Atherosclerosis, a chronic inflammatory disease of large arteries, is the major contributor to the growing burden of cardiovascular disease-related mortality and morbidity. During early atherogenesis, as a result of inflammation and endothelial dysfunction, monocytes transmigrate into the aortic intimal areas, and differentiate into lipid-laden foam cells, a critical process in atherosclerosis. Numerous natural compounds such as flavonoids and polyphenols are known to have anti-inflammatory and anti-atherogenic properties. Read More

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Impaired TRPV4-eNOS signaling in trabecular meshwork elevates intraocular pressure in glaucoma.

Proc Natl Acad Sci U S A 2021 Apr;118(16)

Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107;

Primary Open Angle Glaucoma (POAG) is the most common form of glaucoma that leads to irreversible vision loss. Dysfunction of trabecular meshwork (TM) tissue, a major regulator of aqueous humor (AH) outflow resistance, is associated with intraocular pressure (IOP) elevation in POAG. However, the underlying pathological mechanisms of TM dysfunction in POAG remain elusive. Read More

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The newest TRP channelopathy: Gain of function TRPM3 mutations cause epilepsy and intellectual disability.

Channels (Austin) 2021 Dec;15(1):386-397

Department of Pharmacology, Physiology and Neuroscience, Rutgers, New Jersey Medical School, Newark, NJ, USA.

Transient Receptor Potential Melastatin 3 (TRPM3) is a Ca permeable nonselective cation channel, activated by heat and chemical agonists, such as the endogenous neuro-steroid Pregnenolone Sulfate (PregS) and the chemical compound CIM0216. TRPM3 is expressed in peripheral sensory neurons of the dorsal root ganglia (DRG), and its role in noxious heat sensation in mice is well established. TRPM3 is also expressed in a number of other tissues, including the brain, but its role there has been largely unexplored. Read More

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December 2021

Mitochondrial biogenesis in developing astrocytes regulates astrocyte maturation and synapse formation.

Cell Rep 2021 Apr;35(2):108952

Department of Fundamental Neurosciences, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland; Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, Italy. Electronic address:

The mechanisms controlling the post-natal maturation of astrocytes play a crucial role in ensuring correct synaptogenesis. We show that mitochondrial biogenesis in developing astrocytes is necessary for coordinating post-natal astrocyte maturation and synaptogenesis. The astrocytic mitochondrial biogenesis depends on the transient upregulation of metabolic regulator peroxisome proliferator-activated receptor gamma (PPARγ) co-activator 1α (PGC-1α), which is controlled by metabotropic glutamate receptor 5 (mGluR5). Read More

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C-C motif chemokine ligand 2/C-C receptor 2 is associated with glioma recurrence and poor survival.

Exp Ther Med 2021 Jun 26;21(6):564. Epub 2021 Mar 26.

Department of Radiation Oncology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.

Several studies have explored the mechanisms of C-C motif chemokine ligand (CCL)2/CC receptor (R)2 function in tumorigenesis and inflammation. However, little is known about the role of CCL2/CCR2 in tumor recurrence, especially after radiotherapy. The present study aimed to determine the association between CCL2/CCR2 and glioma relapse. Read More

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Initial clinical evaluation of indigenous Y-DOTATATE in sequential duo-PRRT approach (Lu-DOTATATE and Y-DOTATATE) in neuroendocrine tumors with large bulky disease: Observation on tolerability, Y-DOTATATE post- PRRT imaging characteristics (bremsstrahlung and PETCT) and early adverse effects.

World J Nucl Med 2021 Jan-Mar;20(1):73-81. Epub 2020 Oct 2.

Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Parel, India.

Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) alone has lesser potential in the clinical setting of neuroendocrine tumor (NET) with large bulky disease and nonhomogeneous somatostatin receptors (SSTR) distribution, owing to lower energy (Eβmax 0.497 MeV) and a shorter particle penetration range (maximum 2-4 mm) of Lu. In large bulky NETs, Yttrium (Y) has the theoretical advantages because of a longer beta particle penetration range (a maximum soft tissue penetration of 11 mm). Read More

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October 2020

Comparisons in temperature and photoperiodic-dependent diapause induction between domestic and wild mulberry silkworms.

Sci Rep 2021 Apr 13;11(1):8052. Epub 2021 Apr 13.

Faculty of Textile Science and Technology, Shinshu University, Ueda, Nagano, 386-8567, Japan.

The bivoltine strain of the domestic silkworm, Bombyx mori, has two generations per year. It shows a facultative diapause phenotype determined by environmental conditions, including photoperiod and temperature, and nutrient conditions during embryonic and larval development of the mother. However, it remains unclear how the environmental signals received during development are selectively utilized as cues to determine alternative diapause phenotypes. Read More

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Characterization of combined linagliptin and Y2R agonist treatment in diet-induced obese mice.

Sci Rep 2021 Apr 13;11(1):8060. Epub 2021 Apr 13.

Department of Cardiometabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co., Biberach, Germany.

Dipeptidyl peptidase IV (DPP-IV) inhibitors improve glycemic control by prolonging the action of glucagon-like peptide-1 (GLP-1). In contrast to GLP-1 analogues, DPP-IV inhibitors are weight-neutral. DPP-IV cleavage of PYY and NPY gives rise to PYY and NPY which exert potent anorectic action by stimulating Y2 receptor (Y2R) function. Read More

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Petasin and isopetasin reduce CGRP release from trigeminal afferents indicating an inhibitory effect on TRPA1 and TRPV1 receptor channels.

J Headache Pain 2021 Apr 13;22(1):23. Epub 2021 Apr 13.

Institute of Physiology and Pathophysiology, Friedrich-Alexander-University of Erlangen-Nürnberg, Universitätsstraße 17, 91054, Erlangen, Germany.

Background: Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins on the CGRP release from trigeminal afferents induced by activation of the calcium conducting transient receptor potential channels (TRPs) of the subtypes TRPA1 and TRPV1. Read More

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Cardiac-Specific Deletion of Orai3 Leads to Severe Dilated Cardiomyopathy and Heart Failure in Mice.

J Am Heart Assoc 2021 Apr 14:e019486. Epub 2021 Apr 14.

Department of Physiology University of Tennessee Health Science Center Memphis TN.

Background Orai3 is a mammalian-specific member of the Orai family (Orai1‒3) and a component of the store-operated Ca entry channels. There is little understanding of the role of Orai channels in cardiomyocytes, and its role in cardiac function remains unexplored. Thus, we developed mice lacking Orai1 and Orai3 to address their role in cardiac homeostasis. Read More

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TRPA1 channel: New kid in the 'neurovascular coupling' town.

Cell Calcium 2021 Apr 6;96:102407. Epub 2021 Apr 6.

Department of Pharmacology, University of Vermont, Burlington, VT, USA; Division of Cardiovascular Sciences, University of Manchester, Manchester, UK. Electronic address:

The just-in time delivery of oxygen and nutrients to active brain regions to support function (functional hyperemia; FH) is mediated by not yet fully understood mechanisms collectively referred to as 'neurovascular coupling' (NVC). In a recent publication (eLife 2021) Thakore et al. provide profound mechanistic insight how the capillary endothelial transient receptor potential ankyrin 1 (TRPA1) channel contribute to blood flow control and functional hyperemia in the brain. Read More

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Modulation of stimulated dopamine release in rat nucleus accumbens shell by GABA in vitro: Effect of sub-chronic phencyclidine pretreatment.

J Neurosci Res 2021 Apr 13. Epub 2021 Apr 13.

Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, LE1 9HN, UK.

Dopamine signaling in nucleus accumbens (NAc) is modulated by γ-aminobutyric acid (GABA), acting through GABA-A and GABA-B receptors: dysregulation of GABAergic control of dopamine function may be important in behavioral deficits in schizophrenia. We investigated the effect of GABA-A (muscimol) and GABA-B (baclofen) receptor agonists on electrically stimulated dopamine release. Furthermore, we explored whether drug-induced changes were disrupted by pretreatment with phencyclidine, which provides a well-validated model of schizophrenia. Read More

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Verapamil as an Adjunct Therapy to Reduce tPA Toxicity in Hyperglycemic Stroke: Implication of TXNIP/NLRP3 Inflammasome.

Mol Neurobiol 2021 Apr 13. Epub 2021 Apr 13.

Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee Health Science Center, 875 Monroe Avenue, Wittenborg Bldg, Room-231, Memphis, TN, 38163, USA.

Thrombolytic therapy has remained quite challenging in hyperglycemic patients for its association with poor prognosis and increased hemorrhagic conversions. We recently showed that tissue plasminogen activator (tPA)-induced cerebrovascular damage is associated with thioredoxin-interacting protein (TXNIP) upregulation, which has an established role in the detrimental effects of hyperglycemia. In the present work, we investigated whether verapamil, an established TXNIP inhibitor, may provide protection against hyperglycemic stroke and tPA-induced blood-brain barrier (BBB) disruption. Read More

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