17,241 results match your criteria blockade antagonist


The action of aripiprazole and brexpiprazole at the receptor level in .

J Integr Neurosci 2021 Mar;20(1):247-254

Department of Pharmacology, College of Medicine and Health Science, Khalifa University of Science and Technology, 127788 Abu Dhabi, United Arab Emirates.

The hiccup (Latin ) is an involuntary periodic contraction of the diaphragm followed by glottic closure, which can be a rare side effect of aripiprazole. In contrast to the structurally closely related aripiprazole, brexpiprazole was not associated with this particular adverse drug reaction. Having two very similar drugs that differ in their ability to induce hiccups represents a unique opportunity to gain insight into the receptors involved in the pathophysiology of the symptom and differences in clinical effects between aripiprazole and brexpiprazole. Read More

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Distinct Regulation of Dopamine D3 Receptor in the Basolateral Amygdala and Dentate Gyrus during the Reinstatement of Cocaine CPP Induced by Drug Priming and Social Stress.

Int J Mol Sci 2021 Mar 18;22(6). Epub 2021 Mar 18.

Group of Cellular and Molecular Pharmacology, Department of Pharmacology, University of Murcia, 30120 Murcia, Spain.

Relapse in the seeking and intake of cocaine is one of the main challenges when treating its addiction. Among the triggering factors for the recurrence of cocaine use are the re-exposure to the drug and stressful events. Cocaine relapse engages the activity of memory-related nuclei, such as the basolateral amygdala (BLA) and the hippocampal dentate gyrus (DG), which are responsible for emotional and episodic memories. Read More

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Fatty Acid Synthase Confers Tamoxifen Resistance to ER+/HER2+ Breast Cancer.

Cancers (Basel) 2021 Mar 6;13(5). Epub 2021 Mar 6.

Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, MN 55905, USA.

The identification of clinically important molecular mechanisms driving endocrine resistance is a priority in estrogen receptor-positive (ER+) breast cancer. Although both genomic and non-genomic cross-talk between the ER and growth factor receptors such as human epidermal growth factor receptor 2 (HER2) has frequently been associated with both experimental and clinical endocrine therapy resistance, combined targeting of ER and HER2 has failed to improve overall survival in endocrine non-responsive disease. Herein, we questioned the role of fatty acid synthase (FASN), a lipogenic enzyme linked to HER2-driven breast cancer aggressiveness, in the development and maintenance of hormone-independent growth and resistance to anti-estrogens in ER/HER2-positive (ER+/HER2+) breast cancer. Read More

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Combination of EP antagonist MF-766 and anti-PD-1 promotes anti-tumor efficacy by modulating both lymphocytes and myeloid cells.

Oncoimmunology 2021 Mar 18;10(1):1896643. Epub 2021 Mar 18.

Department of Oncology Early Discovery, Merck & Co., Inc., Boston, Massachusetts, USA.

Prostaglandin E (PGE), an arachidonic acid pathway metabolite produced by cyclooxygenase (COX)-1/2, has been shown to impair anti-tumor immunity through engagement with one or more E-type prostanoid receptors (EP). Specific targeting of EP receptors, as opposed to COX-1/2 inhibition, has been proposed to achieve preferential antagonism of PGE-mediated immune suppression. Here we describe the anti-tumor activity of MF-766, a potent and highly selective small-molecule inhibitor of the EP receptor. Read More

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Leptin antagonism inhibits prostate cancer xenograft growth and progression.

Endocr Relat Cancer 2021 Mar 1. Epub 2021 Mar 1.

C Nelson, Australian Prostate Cancer Research Centre - Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Princess Alexandra Hospital, Translational Research Institute, Queensland University of Technology, Brisbane, Australia.

Hyperleptinemia is a well-established therapeutic side-effect of drugs inhibiting the androgen axis in prostate cancer (PCa), including main stay androgen deprivation therapy (ADT) and androgen targeted therapies (ATT). Given significant crossover between the adipokine hormone signalling of leptin and multiple cancer-promoting hallmark pathways, including growth, proliferation, migration, angiogenesis, metabolism and inflammation, targeting the leptin axis is therapeutically appealing, especially in advanced PCa where current therapies fail to be curative. In this study we uncover leptin as a novel universal target in PCa, and are the first to highlight increased intratumoural leptin and leptin receptor (LEPR) expression in PCa cells and patient tumours exposed to androgen deprivation, as is observed in patient tumours of metastatic and castrate resistant (CRPC) PCa. Read More

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Cannabinoid CB and CB receptors differentially regulate TNF-α-induced apoptosis and LPA-mediated pro-survival signaling in HT22 hippocampal cells.

Life Sci 2021 Mar 29;276:119407. Epub 2021 Mar 29.

Laboratory of Cellular and Molecular Pharmacology, Section of Neurosciences, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy. Electronic address:

Aims: The aim of the study was to investigate the interaction between cannabinoid CB/CB and lysophosphatidic acid (LPA) receptors in controlling neuronal signaling and fate.

Methods: HT22 hippocampal cells were treated with different cannabinoid and LPA receptor agonists and antagonists. Western blot and immunofluorescence microscopy were used to study intracellular signaling and the expression of apoptotic markers. Read More

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Resolvin D1 suppresses inflammation-associated tumorigenesis in the colon by inhibiting IL-6-induced mitotic spindle abnormality.

FASEB J 2021 May;35(5):e21432

Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, South Korea.

While failure in resolution of inflammation is considered to increase the risk of tumorigenesis, there is paucity of experimental as well as clinical evidence supporting this association. Resolvin D1 (RvD1) is a representative pro-resolving lipid mediator that is endogenously generated from docosahexaenoic acid for the resolution of inflammation. Here, we report a decreased level of RvD1 in the blood from colorectal cancer patients and mice having inflammation-induced colon cancer, suggesting plasma RvD1 as a potential biomarker for monitoring colorectal cancer. Read More

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Knowledge-Based Design of Long-Chain Arylpiperazine Derivatives Targeting Multiple Serotonin Receptors as Potential Candidates for Treatment of Autism Spectrum Disorder.

ACS Chem Neurosci 2021 Apr 1. Epub 2021 Apr 1.

Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, via Orabona, 4, 70125 Bari, Italy.

Autism spectrum disorder (ASD) includes a group of neurodevelopmental disorders characterized by core symptoms such as impaired social interaction and communication, repetitive and stereotyped behaviors, and restricted interests. To date, there are no effective treatments for these core symptoms. Several studies have shown that the brain serotonin (5-HT) neurotransmission system is altered in both ASD patients and animal models of the disease. Read More

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Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver.

Dis Model Mech 2021 Mar 28;14(3). Epub 2021 Mar 28.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Japan.

The etiology of non-alcoholic fatty liver disease (NAFLD) consists of various factors, including neural signal pathways. However, the molecular mechanisms of the autonomic neural signals influencing NAFLD progression have not been elucidated. Therefore, we examined the involvement of the gut-liver neural axis in NAFLD development and tested the therapeutic effect of modulation of this axis in this study. Read More

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Neuromodulatory effect of GnRH from coeliac ganglion on luteal regression in the late pregnant rat.

Cell Tissue Res 2021 Mar 29. Epub 2021 Mar 29.

Laboratorio de Biología de la Reproducción (LABIR), Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Instituto Multidisciplinario de Investigaciones Biológicas de San Luis (IMIBIO-SL-CONICET), Av. Ejército de los Andes 950, D5700HHW, San Luis, Argentina.

The GnRH/GnRH receptor system has been found in several extrapituitary tissues, although its physiological significance has not yet been well established. Taking into account that the peripheral neural system can act as a modulator of pregnancy corpus luteum, the objective was to physiologically investigate the presence of the GnRH system in coeliac ganglion (CG) and to analyse its possible involvement in luteal regression through the superior ovarian nerve (SON) at the end of pregnancy in the rat. The integrated ex vivo CG-SON-Ovary system of rats on day 21 of pregnancy was used. Read More

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Propranolol Therapy in Infantile Hemangioma: It Is Not Just About the Beta.

Plast Reconstr Surg 2021 Apr;147(4):875-885

From the Departments of Surgery and Obstetrics and Gynecology, NewYork-Presbyterian Hospital/Columbia University Irving Medical Center.

Background: Propranolol, a nonselective β-adrenergic receptor antagonist, is approved by the U.S. Food and Drug Administration to treat problematic infantile hemangiomas, but a subset of patients experience treatment complications. Read More

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The role of GLP-1 in postprandial glucose metabolism after bariatric surgery: a narrative review of human GLP-1 receptor antagonist studies.

Surg Obes Relat Dis 2021 Feb 9. Epub 2021 Feb 9.

Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.

The Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) bariatric procedures lead to remission or improvement of type 2 diabetes. A weight loss-independent augmentation of postprandial insulin secretion contributes to the improvement in glycemic control after RYGB and is associated with a ∼10-fold increase in plasma concentrations of the incretin hormone glucagon-like peptide-1 (GLP-1). However, the physiologic importance of the markedly increased postprandial GLP-1 secretion after RYGB has been much debated. Read More

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February 2021

Distinct trajectories of antidepressant response to intravenous ketamine.

J Affect Disord 2021 Mar 9;286:320-329. Epub 2021 Mar 9.

Michael E. DeBakey VA Medical Center, 2002 Holcomb Boulevard, Houston, TX, 77030, USA; Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, 1977 Butler Boulevard, Houston, TX, 77030, USA; The Menninger Clinic, 12301 S Main Street, Houston, TX, 77035, USA.

Background: The N-methyl-D-aspartate receptor antagonist ketamine is potentially effective in treatment resistant depression. However, its antidepressant efficacy is highly variable, and there is little information about predictors of response.

Methods: We employed growth mixture modeling (GMM) analysis to examine specific response trajectories to intravenous (IV) ketamine (three infusions; mean dose 0. Read More

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TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome.

Neurosci Bull 2021 Mar 24. Epub 2021 Mar 24.

State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, China.

Nerve agents are used in civil wars and terrorist attacks, posing a threat to public safety. Acute exposure to nerve agents such as soman (GD) causes serious brain damage, leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation. However, data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited. Read More

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Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 2: Attenuation of purinergic bladder smooth muscle contractions.

Am J Physiol Regul Integr Comp Physiol 2021 Mar 24. Epub 2021 Mar 24.

Anatomy and Cell Biology, Temple University, United States.

This study determined the effect of pelvic organ decentralization and reinnervation one year later on the contribution of muscarinic and purinergic receptors to ex-vivo, nerve-evoked, bladder smooth muscle contractions. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7 and hypogastric nerves. After exclusions, 8 were reinnervated 12 months post-decentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers then euthanized 8-12 months later; four served as long-term decentralized only animals. Read More

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Anti- and non-tumor necrosis factor-α-targeted therapies effects on insulin resistance in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

World J Diabetes 2021 Mar;12(3):238-260

Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan.

In addition to β-cell failure with inadequate insulin secretion, the crucial mechanism leading to establishment of diabetes mellitus (DM) is the resistance of target cells to insulin, . insulin resistance (IR), indicating a requirement of beyond-normal insulin concentrations to maintain euglycemic status and an ineffective strength of transduction signaling from the receptor, downstream to the substrates of insulin action. IR is a common feature of most metabolic disorders, particularly type II DM as well as some cases of type I DM. Read More

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Mechanistic insights into the role of the chemokine CCL2/CCR2 axis in dorsal root ganglia to peripheral inflammation and pain hypersensitivity.

J Neuroinflammation 2021 Mar 23;18(1):79. Epub 2021 Mar 23.

Département de Pharmacologie & Physiologie, Institut de Pharmacologie de Sherbrooke, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, Quebec, J1H 5N4, Canada.

Background: Pain is reported as the leading cause of disability in the common forms of inflammatory arthritis conditions. Acting as a key player in nociceptive processing, neuroinflammation, and neuron-glia communication, the chemokine CCL2/CCR2 axis holds great promise for controlling chronic painful arthritis. Here, we investigated how the CCL2/CCR2 system in the dorsal root ganglion (DRG) contributes to the peripheral inflammatory pain sensitization. Read More

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Amino acid systems in the interpeduncular nucleus are altered in a sex-dependent manner during nicotine withdrawal.

J Neurosci Res 2021 Mar 22. Epub 2021 Mar 22.

Department of Psychology, The University of Texas at El Paso, El Paso, TX, USA.

Prior work in male rodents established that the medial habenula-interpeduncular nucleus (MHb-IPN) pathway modulates nicotine withdrawal. Specifically, withdrawal severity has been closely associated with inhibitory tone in the IPN via interneurons that release γ-aminobutyric acid (GABA). Inhibitory tone in the IPN is regulated by projections from the MHb that co-release glutamate and acetylcholine. Read More

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Mineralocorticoid receptor blockade with finerenone improves heart function and exercise capacity in ovariectomized mice.

ESC Heart Fail 2021 Mar 20. Epub 2021 Mar 20.

Inserm U1096 ENVI, Rouen Medical School, UNIROUEN, Normandy University, Rouen, France.

Aims: In post-menopausal women, incidence of heart failure with preserved ejection fraction is higher than in men. Hormonal replacement therapies did not demonstrate benefits. We tested whether the non-steroidal mineralocorticoid receptor antagonist finerenone limits the progression of heart failure in ovariectomized (OVX) mice with metabolic disorders. Read More

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Recent trend of ADT in newly-diagnosed prostate cancer patients: comparing between high- and middle income Asian countries.

Cancer Sci 2021 Mar 19. Epub 2021 Mar 19.

Strategic Investigation on Comprehensive Cancer Network, Interfaculty Initiative in Information Studies / Graduate School of Interdisciplinary Information, University of Tokyo, Tokyo, Japan.

The number of newly-diagnosed prostate cancer cases varies across Asia with higher mortality-to-incidence ratio reported in developing nations. Androgen deprivation therapy (ADT), alone or in combination, remains the mainstay of first-line treatment for advanced prostate cancer. Key findings of extensive research and randomised-controlled trials have shaped the current clinical practice and influenced clinical guidelines recommendations. Read More

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Activation and blockade of dorsal hippocampal serotonin4 receptors produce antidepressant effects in the hemiparkinsonian rats.

Brain Res 2021 Mar 15:147426. Epub 2021 Mar 15.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China; The Key Laboratory of Environment and Disease-Related Genes, Ministry of Education, Xi'an 710061, China. Electronic address:

Depression is a common non-motor symptom in Parkinson's disease (PD). Although serotonin4 (5-HT) receptors and the dorsal hippocampus (dHIP) are regarded to be involved in the depression, the mechanism underlying the effects of 5-HT receptors in the dHIP on PD-related depression should be further investigated. In the present study, unilateral 6-hydroxydopamine lesions of the medial forebrain bundle (MFB) increased the expressions of 5-HT receptors and its co-localization with glutamate neurons in the CA1, CA3 and dentate gyrus. Read More

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Selective blockade of transient receptor potential vanilloid 4 reduces cyclophosphamide-induced bladder pain in mice.

Eur J Pharmacol 2021 Mar 15;899:174040. Epub 2021 Mar 15.

Laboratory for Drug Discovery & Disease Research, Shionogi & Co., Ltd., 1-1 Futaba-cho 3-chome, Toyonaka, Osaka, 561-0825, Japan. Electronic address:

Transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel activated by various physical stimuli such as cell swelling and shear stress. TRPV4 is expressed in bladder sensory nerves and epithelium, and its activation produces urinary dysfunction in rodents. However, there have been few reports regarding its involvement in bladder pain. Read More

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GPR18 drives FAAH inhibition-induced neuroprotection against HIV-1 Tat-induced neurodegeneration.

Exp Neurol 2021 Mar 15;341:113699. Epub 2021 Mar 15.

Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America. Electronic address:

Human immunodeficiency virus type 1 (HIV-1) is known to provoke microglial immune responses which likely play a paramount role in the development of chronic neuroinflammatory conditions and neuronal damage related to HIV-1 associated neurocognitive disorders (HAND). In particular, HIV-1 Tat protein is a proinflammatory neurotoxin which predisposes neurons to synaptodendritic injury. Drugs targeting the degradative enzymes of endogenous cannabinoids have shown promise in reducing inflammation with minimal side effects in rodent models. Read More

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Crosstalk Between ATP-P and Adenosine A Receptors Controlling Neuroinflammation in Rats Subject to Repeated Restraint Stress.

Front Cell Neurosci 2021 1;15:639322. Epub 2021 Mar 1.

CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.

Depressive conditions precipitated by repeated stress are a major socio-economical burden in Western countries. Previous studies showed that ATP-P receptors (PR) and adenosine A receptors (AR) antagonists attenuate behavioral modifications upon exposure to repeated stress. Since it is unknown if these two purinergic modulation systems work independently, we now investigated a putative interplay between PR and AR. Read More

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Modulating Ocular Surface Pain Through Neurokinin-1 Receptor Blockade.

Invest Ophthalmol Vis Sci 2021 Mar;62(3):26

Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Purpose: The purpose of this study was to test the role of substance P (SP) and its receptor neurokinin 1 (NK1R) on ocular surface pain.

Methods: Eight-week-old C57BL6/N (wild type [WT]) and B6.Cg-Tac1tm1Bbm/J (TAC1-KO) male mice were used. Read More

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Nicotine withdrawal induces hyperalgesia via downregulation of descending serotonergic pathway in the nucleus raphe magnus.

Neuropharmacology 2021 Mar 17;189:108515. Epub 2021 Mar 17.

Department of Anesthesiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, China. Electronic address:

Patients deprived of cigarettes exhibit increased pain sensitivity during perioperative periods, yet the underlying neuroanatomical and molecular bases of this hypersensitivity are unclear. The present study showed that both the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were significantly decreased in a rat model of nicotine withdrawal. These rats showed less tryptophan hydroxylase 2 (TPH2) positive neurons and reduced TPH2 expression in the nucleus raphe magnus (NRM), and thus resulted in decreased 5-hydroxytryptamine (5-HT) levels in cerebrospinal fluid. Read More

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The Crucial Role of PPARγ-Egr-1-Pro-Inflammatory Mediators Axis in IgG Immune Complex-Induced Acute Lung Injury.

Front Immunol 2021 25;12:634889. Epub 2021 Feb 25.

Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and Integrated Chinese and Western Medicine (ITCWM) Repair, Institute of Integrative Medicine for Acute Abdominal Diseases, Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin, China.

Background: The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR) γ plays crucial roles in diverse biological processes including cellular metabolism, differentiation, development, and immune response. However, during IgG immune complex (IgG-IC)-induced acute lung inflammation, its expression and function in the pulmonary tissue remains unknown.

Objectives: The study is designed to determine the effect of PPARγ on IgG-IC-triggered acute lung inflammation, and the underlying mechanisms, which might provide theoretical basis for therapy of acute lung inflammation. Read More

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February 2021

'Defrosting' music chills with naltrexone: The role of endogenous opioids for the intensity of musical pleasure.

Conscious Cogn 2021 Apr 10;90:103105. Epub 2021 Mar 10.

Department of Psychology, University of Oslo, Oslo, Norway; Department of Diagnostic Physics, Oslo University Hospital, Norway.

The endogenous opioid system has been implicated during experiences of pleasure (i.e., from food or sex). Read More

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Interleukin-1 Blockade in Polygenic Autoinflammatory Disorders: Where Are We now?

Front Pharmacol 2020 26;11:619273. Epub 2021 Jan 26.

Department of Paediatric and Adult Rheumatology, University Hospital Motol, Prague, Czechia.

Polygenic autoinflammatory diseases (AIDs), such as systemic juvenile idiopathic arthritis (sJIA), adult-onset Still's disease, Kawasaki disease, idiopathic recurrent pericarditis (IRP), Behçet's Syndrome, Crystal-induced arthropatihes such as gout or Calcium pyrophosphate deposition disease are characterized by the overexpression of inflammasome-associated genes, leading to a dysregulation of the innate immune response. The IL-1 cytokine family (IL-1α, IL-1β, IL-1Ra, IL-18, IL-36Ra, IL-36α, IL-37, IL-36β, IL-36g, IL-38, IL-33) was defined to be principally responsible for the inflammatory nature of polygenic AIDs. Several clinical trials were initiated, and IL-1 blockade has been proven to cause a rapid reduction of clinical symptoms and normalization of laboratory parameters in the majority of cases. Read More

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January 2021

Inhibition of PACAP/PAC1/VPAC2 signaling impairs the consolidation of social recognition memory and nitric oxide prevents this deficit.

Neurobiol Learn Mem 2021 Mar 9;180:107423. Epub 2021 Mar 9.

Memory Center, Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6690-2nd Floor, 90610-000 Porto Alegre, RS, Brazil; National Institute of Translational Neuroscience (INNT), National Research Council of Brazil, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil. Electronic address:

Social recognition memory (SRM) forms the basis of social relationships of animals. It is essential for social interaction and adaptive behavior, reproduction and species survival. Evidence demonstrates that social deficits of psychiatric disorders such as autism and schizophrenia are caused by alterations in SRM processing by the hippocampus and amygdala. Read More

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