36,034 results match your criteria selective agonist


Functional and Anatomical Characterization of Corticotropin-Releasing Factor Receptor Subtypes of the Rat Spinal Cord Involved in Somatic Pain Relief.

Mol Neurobiol 2021 Jul 31. Epub 2021 Jul 31.

Department of Anesthesiology and Operative Intensive Care Medicine, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany.

Corticotropin-releasing factor (CRF) orchestrates our body's response to stressful stimuli. Pain is often stressful and counterbalanced by activation of CRF receptors along the nociceptive pathway, although the involvement of the CRF receptor subtypes 1 and/or 2 (CRF-R1 and CRF-R2, respectively) in CRF-induced analgesia remains controversial. Thus, the aim of the present study was to examine CRF-R1 and CRF-R2 expression within the spinal cord of rats with Freund's complete adjuvant-induced unilateral inflammation of the hind paw using reverse transcriptase polymerase chain reaction, Western blot, radioligand binding, and immunofluorescence confocal analysis. Read More

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J Pharmacol Exp Ther 2021 Jul 30. Epub 2021 Jul 30.

Department of Cellular and Molecular Medicine, University of Ottawa, Canada

Huntington's Disease (HD) is an autosomal dominant neurodegenerative disease that leads to progressive motor impairment with no available disease-modifying treatments. Current evidence indicates that exacerbated postsynaptic glutamate signaling in the striatum plays a key role in the pathophysiology of HD. However, it remains unclear whether reducing glutamate release can be an effective approach to slow the progression of HD. Read More

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Thromboxane-prostanoid receptor activation blocks ATP-sensitive potassium channels in rat aortas.

Clin Exp Pharmacol Physiol 2021 Jul 30. Epub 2021 Jul 30.

Dept. of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo.

K channel activation is one of the major mechanisms involved in vasodilation. Vasoconstrictor agonists such as angiotensin II promote ATP-dependent potassium channels (K ) dysfunction. This study evaluates whether Thromboxane-prostanoid (TP receptor) activation by the agonist U46619 increases reactive oxygen species (ROS) production in rat aortas, which could contribute to K channel dysfunction and impaired NO-dependent vasodilation. Read More

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In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells.

Sci Rep 2021 Jul 29;11(1):15437. Epub 2021 Jul 29.

Department of Prosthodontics, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta-ku, Tokyo, 145-8515, Japan.

The serotonin 5-HT receptor (5-HTR) has been receiving increasing attention because its genetic variants have been associated with a variety of neurological diseases. To elucidate the pathogenesis of the neurological diseases associated with 5-HTR gene (HTR2A) variants, we have previously established a protocol to induce HTR2A-expressing neurons from human-induced pluripotent stem cells (hiPSCs). Here, we investigated the maturation stages and electrophysiological properties of HTR2A-positive neurons induced from hiPSCs and constructed an HTR2A promoter-specific reporter lentivirus to label the neurons. Read More

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Activation of microglial GLP-1R in the trigeminal nucleus caudalis suppresses central sensitization of chronic migraine after recurrent nitroglycerin stimulation.

J Headache Pain 2021 Jul 29;22(1):86. Epub 2021 Jul 29.

Department of Histology and Embryology, Chongqing Medical University, No.1 Yixueyuan Road, Yuzhong District, 400016, Chongqing, China.

Background: Central sensitization is considered a critical pathogenic mechanism of chronic migraine (CM). Activation of microglia in the trigeminal nucleus caudalis (TNC) contributes to this progression. Microglial glucagon-like peptide-1 receptor (GLP-1R) activation can alleviate pain; however, whether it is involved in the mechanism of CM has not been determined. Read More

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REV-ERBα agonist SR9009 suppresses IL-1β production in macrophages through BMAL1-dependent inhibition of inflammasome.

Biochem Pharmacol 2021 Jul 26:114701. Epub 2021 Jul 26.

School of Biomedical Sciences, CUHK Shenzhen Research Institute, Heart and Vascular Institute, Chinese University of Hong Kong, Hong Kong SAR. Electronic address:

The circadian clock plays an important role in adapting organisms to the daily light/dark cycling environment. Recent research findings reveal the involvement of the circadian clock not only in physiological functions but also in regulating inflammatory responses under pathological situations. Previous studies showed that the time-of-day variance of leucocyte circulation and pro-inflammatory cytokines secretion could be directly regulated by the clock-related proteins, including BMAL1 and REV-ERBα in a 24-hour oscillation pattern. Read More

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Mechanical and chemical activation of GPR68 (OGR1) probed with a genetically-encoded fluorescent reporter.

J Cell Sci 2021 Jul 29. Epub 2021 Jul 29.

Graduate College of Biomedical Sciences, Western University of Health Sciences, 309 E. Second St, Pomona, CA 91766, USA.

G-protein coupled receptor (GPCR) 68 (GPR68, or OGR1) couples extracellular acidifications and mechanical stimuli to G-protein signaling and plays important roles in vascular physiology, neuroplasticity, and cancer progression. Inspired by previous GPCR-based reporters, here, we inserted a cyclic permuted fluorescent protein into the third intracellular loop of GPR68 to create a genetically-encoded fluorescent reporter of GPR68 activation we call "iGlow". iGlow responds to known physiological GPR68 activators such as fluid shear stress and extracellular acidifications. Read More

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Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4.

Front Immunol 2021 12;12:695933. Epub 2021 Jul 12.

Department of Experimental and Clinical Pharmacology and Pharmacogenomics, University Hospital Tübingen, Tübingen, Germany.

Emerging evidence suggests a mechanistic role for myeloid-derived suppressor cells (MDSCs) in lung diseases like asthma. Previously, we showed that adoptive transfer of MDSCs dampens lung inflammation in murine models of asthma through cyclooxygenase-2 and arginase-1 pathways. Here, we further dissected this mechanism by studying the role and therapeutic relevance of the downstream mediator prostaglandin E2 receptor 4 (EP4) in a murine model of asthma. Read More

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Case Report: Dexmedetomidine for Intractable Clusters of Myoclonic Jerks and Paroxysmal Sympathetic Hyperactivity in Progressive Encephalomyelitis With Rigidity and Myoclonus.

Front Neurol 2021 12;12:703050. Epub 2021 Jul 12.

Department of Neurology, Kitasato University School of Medicine, Sagamihara, Japan.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder characterized by painful spasms, myoclonic jerks, hyperekplexia, brainstem dysfunction, and dysautonomia, which is sometimes resistant to γ-amino-butyric acid (GABA)-ergic agents. The response to immunotherapy varies depending on identified autoantibodies. We report a dramatic response to dexmedetomidine in a patient with glycine receptor (GlyR) antibody-positive PERM who developed intractable clusters of myoclonic jerks and paroxysmal sympathetic hyperactivity (PSH) that was highly refractory to conventional symptomatic treatment with GABAergic drugs and immunotherapy. Read More

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

Biomed Pharmacother 2020 Oct 1;130:110654. Epub 2020 Sep 1.

Department of Ophthalmology, Lixiang Eye Hospital of Soochow University, Suzhou, Jiangsu, China. Electronic address:

Neovascular age-related macular degeneration (nAMD), featured as choroidal neovascularization (CNV), can cause blindness in the elderly population. MLN4924, a highly selective small-molecule inhibitor of NEDD8 (neuronal precursor cell-expressed developmentally down-regulated protein 8)-activating enzyme (NAE), inhibits the proliferation, angiogenesis and inflammation of multiple cancers via up-regulating hedgehog pathway-regulated autophagy. MLN4924 intraperitoneal injection mitigated the leakage, area and volume of mouse laser-induced CNV lesion. Read More

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October 2020

Macrophage depletion increases target specificity of bone-targeted nanoparticles.

J Biomed Mater Res A 2021 Jul 28:e37279. Epub 2021 Jul 28.

Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA.

Despite efforts to achieve tissue selectivity, the majority of systemically administered drug delivery systems (DDSs) are cleared by the mononuclear phagocyte system (MPS) before reaching target tissues regardless of disease or injury pathology. Previously, we showed that while tartrate-resistant acid phosphatase (TRAP) binding peptide (TBP)-targeted polymeric nanoparticles (TBP-NP) delivering a bone regenerative Wnt agonist improved NP fracture accumulation and expedited healing compared with controls, there was also significant MPS accumulation. Here we show that TBP-NPs are taken up by liver, spleen, lung, and bone marrow macrophages (Mϕ), with 76 ± 4%, 49 ± 11%, 27 ± 9%, and 92 ± 5% of tissue-specific Mϕ positive for NP, respectively. Read More

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Cryo-EM structure of the β3-adrenergic receptor reveals the molecular basis of subtype selectivity.

Mol Cell 2021 Jul 21. Epub 2021 Jul 21.

Department of Biological Sciences, Graduate School of Science, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address:

The β-adrenergic receptor (βAR) is predominantly expressed in adipose tissue and urinary bladder and has emerged as an attractive drug target for the treatment of type 2 diabetes, obesity, and overactive bladder (OAB). Here, we report the cryogenic electron microscopy structure of the βAR-G signaling complex with the selective agonist mirabegron, a first-in-class drug for OAB. Comparison of this structure with the previously reported βAR and βAR structures reveals a receptor activation mechanism upon mirabegron binding to the orthosteric site. Read More

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Isolation, identification, and activity evaluation of diterpenoid alkaloids from Aconitum sinomontanum.

Phytochemistry 2021 Jul 23;190:112880. Epub 2021 Jul 23.

State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China. Electronic address:

A phytochemical study led to the isolation of 25 diterpenoid alkaloids from Aconitum sinomontanum, of which six were described for the first time. Among them compounds 1-3 are anhydrolycoctonine derivatives, rare rearranged aconitine-type C-diterpenoid alkaloids. To our best knowledge, less than ten of this type of alkaloids were isolated just from the genus Aconitum. Read More

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Selective Estrogen Receptor Modulators in Gynecology Practice.

Clin Obstet Gynecol 2021 Jul 23. Epub 2021 Jul 23.

Department of Obstetrics and Gynecology, Division of Midlife Health, University of Virginia Health System, Charlottesville, Virginia.

Selective estrogen receptor (ER) modulators have variable tissue specific estrogen agonist and antagonist activities. Tamoxifen is approved for treatment and prevention of breast cancer; acts as an endometrial estrogen agonist. Raloxifene is approved for prevention and treatment of osteoporosis and prevention of breast cancer. Read More

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The Evolving Story of Incretins (GIP and GLP-1) in Metabolic and Cardiovascular Disease: A Pathophysiological Update.

Diabetes Obes Metab 2021 Jul 26. Epub 2021 Jul 26.

Charité - Universitätsmedizin Berlin, Klinik für Endokrinologie, Stoffwechsel- und Ernährungsmedizin, Berlin, Germany.

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have their main physiological role in augmenting insulin secretion after their nutrient-induced secretion from the gut. A functioning entero-insular (gut-endocrine pancreas) axis is essential for the maintenance of a normal glucose tolerance. This is exemplified by the incretin effect (greater insulin secretory response to oral as compared to "isoglycaemic" intravenous glucose administration due to the secretion and action of incretin hormones). Read More

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Plant-Derived Cyclotides Modulate κ-Opioid Receptor Signaling.

J Nat Prod 2021 Jul 26. Epub 2021 Jul 26.

Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.

Cyclotides are plant-derived disulfide-rich peptides comprising a cyclic cystine knot, which confers remarkable stability against thermal, proteolytic, and chemical degradation. They represent an emerging class of G protein-coupled receptor (GPCR) ligands. In this study, utilizing a screening approach of plant extracts and pharmacological analysis we identified cyclotides from to be ligands of the κ-opioid receptor (KOR), an attractive target for developing analgesics with reduced side effects and therapeutics for multiple sclerosis (MS). Read More

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Hemiplegic migraine episode triggered by regadenoson.

J Nucl Cardiol 2021 Jul 25. Epub 2021 Jul 25.

Division of Cardiology, Hartford Hospital, 80 Seymour Street, Hartford, CT, 06102, USA.

SPECT and PET myocardial perfusion imaging (MPI) are widely used to evaluate patients for coronary artery disease. Regadenoson (a selective A adenosine receptor agonist) is a commonly used vasodilator agent for stress MPI because of its safety profile and ease of use. Common adverse reactions such as headache, shortness of breath, flushing, and chest and abdominal discomfort are typically mild and can be effectively reversed using methylxanthines such as aminophylline and caffeine. Read More

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Treatment of leiomyomatosis peritonealis disseminata with goserelin acetate: A case report and review of the literature.

World J Clin Cases 2021 Jul;9(19):5217-5225

Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Discipline Construction Research Center of China Hospital Development Institute, Shanghai Jiao Tong University, Shanghai 200011, China.

Background: Leiomyomatosis peritonealis disseminata (LPD) is a rare condition characterized by multiple pelvic and abdominal nodules, which are composed of smooth-muscle cells. To date, no more than 200 cases have been reported. The diagnosis of LPD is difficult and there are no guidelines on the treatment of LPD. Read More

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Glucagon-Like Peptide-1 Receptor Agonist Ameliorates 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Neurotoxicity Through Enhancing Mitophagy Flux and Reducing α-Synuclein and Oxidative Stress.

Front Mol Neurosci 2021 7;14:697440. Epub 2021 Jul 7.

Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Parkinson disease (PD) is the second most common neurodegenerative disease without known disease modification therapy to slow down disease progression. This disease has pathological features of Lewy bodies with α-synuclein aggregation being the major component and selective dopaminergic neuronal loss over the substantia nigra. Although the exact etiology is still unknown, mitochondrial dysfunction has been shown to be central in PD pathophysiology. Read More

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Protein Binding and Population Pharmacokinetics of Dexmedetomidine after Prolonged Infusions in Adult Critically Ill Patients.

Clin Ther 2021 Jul 22. Epub 2021 Jul 22.

Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.

Purpose: Dexmedetomidine (DEX) is a highly selective α-adrenoceptor agonist with high protein binding of 94%. Critical illness may affect protein binding and the pharmacokinetic (PK) parameters of many drugs, including DEX. In critically ill patients receiving prolonged infusions of DEX, there is little information documenting the relationship between key pathophysiologic factors and DEX protein binding or PK parameters. Read More

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Drug interaction between a selective serotonin reuptake inhibitor and a triptan leading to serotonin toxicity: a case report and review of the literature.

J Med Case Rep 2021 Jul 26;15(1):371. Epub 2021 Jul 26.

Redcliffe Hospital, Anzac Avenue, Redcliffe, QLD, 4020, Australia.

Background: Serotonin toxicity is a known side effect of selective serotonin reuptake inhibitors and has previously also been described as a possible side effect of 5-hydroxytryptamine receptor agonist (triptan) medications. However, the literature is conflicted about the risk of developing serotonin toxicity as a result of drug interaction between selective serotonin reuptake inhibitors and triptans.

Case Presentation: A 30-year-old Caucasian woman with a history of depression on regular fluvoxamine presented to the emergency department with right-sided facial and lower limb twitching. Read More

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Endothelial BBSome is Essential for Vascular, Metabolic, and Retinal Functions.

Mol Metab 2021 Jul 22:101308. Epub 2021 Jul 22.

Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Obesity Research and Educational Initiative, University of Iowa Carver College of Medicine, Iowa City, IA, USA; Iowa City VA Health Care System, Iowa City, IA. Electronic address:

Objectives: - Endothelial cells that line the entire vascular system play a pivotal role in the control of various physiological processes including metabolism. Moreover, endothelial dysfunction is associated with many pathological conditions including obesity. Here, we assessed the role of the BBSome, a protein complex composed of eight Bardet-Biedl syndrome (BBS) proteins including BBS1, in endothelial cells. Read More

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Therapeutic Targeting of 7 Nicotinic Acetylcholine Receptors.

Pharmacol Rev 2021 Jul;73(3):1118-1149

Departments of Pharmacology and Therapeutics (R.L.P) and Chemistry (N.A.H.), University of Florida, Gainesville, FL.

The 7-type nicotinic acetylcholine receptor is one of the most unique and interesting of all the members of the cys-loop superfamily of ligand-gated ion channels. Since it was first identified initially as a binding site for -bungarotoxin in mammalian brain and later as a functional homomeric receptor with relatively high calcium permeability, it has been pursued as a potential therapeutic target for numerous indications, from Alzheimer disease to asthma. In this review, we discuss the history and state of the art for targeting 7 receptors, beginning with subtype-selective agonists and the basic pharmacophore for the selective activation of 7 receptors. Read More

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Acute Lung Injury in Cholinergic-Deficient Mice Supports Anti-Inflammatory Role of α7 Nicotinic Acetylcholine Receptor.

Int J Mol Sci 2021 Jul 14;22(14). Epub 2021 Jul 14.

Department of Bioscience, Federal University of Sao Paulo, Santos 11015-020, SP, Brazil.

(1) Background: The lung cholinergic pathway is important for controlling pulmonary inflammation in acute lung injury, a condition that is characterized by a sudden onset and intense inflammation. This study investigated changes in the expression levels of nicotinic and muscarinic acetylcholine receptors (nAChR and mAChR) in the lung during acute lung injury. (2) Methods: acute lung injury (ALI) was induced in wild-type and cholinergic-deficient (VAChT-KD) mice using intratracheal lipopolysaccharide (LPS) instillation with or without concurrent treatment with nicotinic ligands. Read More

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Curcumin Potentiates α7 Nicotinic Acetylcholine Receptors and Alleviates Autistic-Like Social Deficits and Brain Oxidative Stress Status in Mice.

Int J Mol Sci 2021 Jul 6;22(14). Epub 2021 Jul 6.

Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Kuwait University, Safat 13110, Kuwait.

Autistic spectrum disorder (ASD) refers to a group of neurodevelopmental disorders characterized by impaired social interaction and cognitive deficit, restricted repetitive behaviors, altered immune responses, and imbalanced oxidative stress status. In recent years, there has been a growing interest in studying the role of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in the CNS. Influence of agonists for α7-nAChRs on the cognitive behavior, learning, and memory formation has been demonstrated in neuro-pathological condition such as ASD and attention-deficit hyperactivity disorder (ADHD). Read More

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Selective blood-brain barrier permeabilisation of brain metastases by a type-1 receptor selective tumour necrosis factor mutein.

Neuro Oncol 2021 Jul 23. Epub 2021 Jul 23.

Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK.

Background: Metastasis to the brain is a major challenge with poor prognosis. The blood-brain barrier (BBB) is a significant impediment to effective treatment, being intact during the early stages of tumour development and heterogeneously permeable at later stages. Intravenous injection of tumour necrosis factor (TNF) selectively induces BBB permeabilisation at sites of brain micrometastasis, in a TNF type-1 receptor (TNFR1) dependent manner. Read More

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Relationship Between the Activities of Gloss-Selective Neurons in the Macaque Inferior Temporal Cortex and the Gloss Discrimination Behavior of the Monkey.

Cereb Cortex Commun 2021 10;2(1):tgab011. Epub 2021 Feb 10.

Brain Science Institute, Tamagawa University, Tokyo 194-8610, Japan.

In the macaque monkey, neurons that selectively respond to specific gloss are present in a restricted region of the central part of the inferior temporal (IT) cortex. Although the population activity of these neurons is known to represent the perceptual gloss space, the involvement of their activity in gloss perception has not been directly tested. In the present study, we examined the causal relationship between the activities of gloss-selective neurons and gloss perception by applying electrical microstimulation or injection of small amounts of muscimol (GABA agonist) to manipulate neural activities while monkeys performed a gloss discrimination task. Read More

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February 2021

Mitochondrial estrogen receptors alter mitochondrial priming and response to endocrine therapy in breast cancer cells.

Cell Death Discov 2021 Jul 22;7(1):189. Epub 2021 Jul 22.

Baskent University School of Medicine, Dept. of Immunology, Adana Dr. Turgut Noyan Medical and Research Center, Adana, Turkey.

Breast cancer is the most common cancer with a high rate of mortality and morbidity among women worldwide. Estrogen receptor status is an important prognostic factor and endocrine therapy is the choice of first-line treatment in ER-positive breast cancer. However, most tumors develop resistance to endocrine therapy. Read More

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Agomelatine prevents angiotensin II-induced endothelial and mononuclear cell adhesion.

Aging (Albany NY) 2021 Jul 22;13(undefined). Epub 2021 Jul 22.

Department of Stomatology, Tibet Corps Hospital, Chinese People's Armed Police Forces, Lhasa 850000, Tibet Autonomous Region, China.

Agomelatine is a non-selective melatonin receptor agonist and an atypical antidepressant with anti-inflammatory, neuroprotective, and cardioprotective effects. The renin-angiotensin system modulates blood pressure and vascular homeostasis. Angiotensin II (Ang II) and its receptor Ang II type I receptor (ATR) are recognized as contributors to the pathogenesis of cardiovascular and cardiometabolic diseases, including diabetes, obesity, and atherosclerosis. Read More

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