Search results for "antagonist"
showing 10 items of 1660 documents
Glutamate and opioid antagonists modulate dopamine levels evoked by innately attractive male chemosignals in the nucleus accumbens of female rats
2017
Sexual chemosignals detected by vomeronasal and olfactory systems mediate intersexual attraction in rodents, and act as a natural reinforcer to them. The mesolimbic pathway processes natural rewards, and the nucleus accumbens receives olfactory information via glutamatergic projections from the amygdala. Thus, the aim of this study was to investigate the involvement of the mesolimbic pathway in the attraction toward sexual chemosignals. Our data show that female rats with no previous experience with males or their chemosignals display an innate preference for male-soiled bedding. Focal administration of the opioid antagonist b-funaltrexamine into the posterior ventral tegmental area does no…
Blocking CGRP in migraine patients â a review of pros and cons
2017
Abstract Migraine is the most prevalent neurological disorder worldwide and it has immense socioeconomic impact. Currently, preventative treatment options for migraine include drugs developed for diseases other than migraine such as hypertension, depression and epilepsy. During the last decade, however, blocking calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for prevention of migraine attacks. CGRP has been shown to be released during migraine attacks and it may play a causative role in induction of migraine attacks. Here, we review the pros and cons of blocking CGRP in migraine patients. To date, two different classes of drugs blocking CGRP have been developed: …
Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht Consensus Conference on Thrombosis
2018
AbstractAtherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1. Risk factors, biomarkers and plaque inst…
Regular Intake of Pistachio Mitigates the Deleterious Effects of a High Fat-Diet in the Brain of Obese Mice
2020
Obesity has been associated with neurodegeneration and cognitive dysfunctions. Recent data showed that pistachio consumption is able to prevent and ameliorate dyslipidemia, hepatic steatosis, systemic and adipose tissue inflammation in mice fed a high-fat diet (HFD). The present study investigated the neuroprotective effects of pistachio intake in HFD mice. Three groups of mice were fed a standard diet (STD), HFD, or HFD supplemented with pistachio (HFD-P) for 16 weeks. Metabolic parameters (oxidative stress, apoptosis, and mitochondrial dysfunction) were analyzed by using specific assays and biomarkers. The pistachio diet significantly reduced the serum levels of triglycerides and choleste…
Does sex hormone-binding globulin cause insulin resistance during pubertal growth?
2019
Background The directional influences between serum sex hormone-binding globulin (SHBG), adiposity and insulin resistance during pubertal growth remain unclear. The aim of this study was to investigate bidirectional associations between SHBG and insulin resistance (HOMA-IR) and adiposity from childhood to early adulthood. Methods Participants were 396 healthy girls measured at baseline (age 11.2 years) and at 1, 2, 4 and 7.5 years. Serum concentrations of estradiol, testosterone and SHBG were determined by ELISA, glucose and insulin by enzymatic photometry, insulin-like growth factor 1 (IGF-1) by time-resolved fluoroimmunoassays, whole-body fat mass by dual-energy X-ray absorptiometry and …
Famotidine inhibits toll-like receptor 3-mediated inflammatory signaling in SARS-CoV-2 infection
2021
Apart from prevention using vaccinations, the management options for COVID-19 remain limited. In retrospective cohort studies, use of famotidine, a specific oral H2 receptor antagonist (antihistamine), has been associated with reduced risk of intubation and death in patients hospitalized with COVID-19. In a case series, nonhospitalized patients with COVID-19 experienced rapid symptom resolution after taking famotidine, but the molecular basis of these observations remains elusive. Here we show using biochemical, cellular, and functional assays that famotidine has no effect on viral replication or viral protease activity. However, famotidine can affect histamine-induced signaling processes i…
Discovery of Natural Products as Novel and Potent FXR Antagonists by Virtual Screening
2018
Farnesoid X receptor (FXR) is a member of nuclear receptor family involved in multiple physiological processes through regulating specific target genes. The critical role of FXR as a transcriptional regulator makes it a promising target for diverse diseases, especially those related to metabolic disorders such as diabetes and cholestasis. However, the underlying activation mechanism of FXR is still a blur owing to the absence of proper FXR modulators. To identify potential FXR modulators, an in-house natural product database (NPD) containing over 4,000 compounds was screened by structure-based virtual screening strategy and subsequent hit-based similarity searching method. After the yeast t…
Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth
2012
International audience; Chemotherapeutic agents are widely used for cancer treatment. In addition to their direct cytotoxic effects, these agents harness the host's immune system, which contributes to their antitumor activity. Here we show that two clinically used chemotherapeutic agents, gemcitabine (Gem) and 5-fluorouracil (5FU), activate the NOD-like receptor family, pyrin domain containing-3 protein (Nlrp3)-dependent caspase-1 activation complex (termed the inflammasome) in myeloid-derived suppressor cells (MDSCs), leading to production of interleukin-1β (IL-1β), which curtails anticancer immunity. Chemotherapy-triggered IL-1β secretion relied on lysosomal permeabilization and the relea…
Human POMC processing in vitro and in vivo revealed by quantitative peptidomics
2018
ABSTRACTHuman obesity can result from the aberrant production or processing of proopiomelanocortin (POMC) in hypothalamic neurons, but it is unclear which human POMC-derived peptides are most relevant to body weight regulation. To address this question, we analysed both hypothalamic neurons derived from human pluripotent stem cells (hPSCs) and primary human hypothalamic tissue using quantitative liquid chromatography tandem mass spectroscopy (LC-MS/MS). In both in vitro- and in vivo-derived samples, we found that POMC was processed into β-melanocyte stimulating hormone (β-MSH), whose existence in the human brain has been controversial. β-MSH and desacetyl α-MSH (d-α-MSH) were produced at ro…
Estrogen Regulates the Satellite Cell Compartment in Females
2018
SUMMARYSkeletal muscle mass, strength, and regenerative capacity decline with age, with many measures showing greater deterioration in females about the time estrogen levels decrease at menopause. Here we show that maintenance of muscle stem cells, satellite cells, as well as self-renewal and differentiation into muscle fibers, are severely compromised by estrogen deficiency. Mechanistically, by hormone replacement, use of a selective estrogen-receptor modulator (bazedoxifene), and conditional estrogen receptor knockout, we implicate 17β-estradiol and satellite cell expression of estrogen receptorα(ERα) and show that estrogen signaling through this receptor is necessary to prevent apoptosis…