Trypsin inhibitors are studied in a variety of models for their anti-obesity and anti-inflammatory bioactive properties. Our group has previously demonstrated the satietogenic effect of tamarind seed trypsin inhibitors (TTI) in eutrophic mouse models and anti-inflammatory effects of other trypsin inhibitors. In this study, we evaluated TTI effect upon satiety, biochemical and inflammatory parameters in an experimental model of metabolic syndrome (MetS). Three groups of n = 5 male Wistar rats with obesity-based MetS received for 10 days one of the following: (1) Cafeteria diet; (2) Cafeteria diet + TTI (25 mg/kg); and (3) Standard diet. TTI reduced food intake in animals with MetS. Nevertheless, weight gain was not different between studied groups. Dyslipidemia parameters were not different with the use of TTI, only the group receiving standard diet showed lower very low density lipoprotein (VLDL) and triglycerides (TG) (Kruskal–Wallis, p < 0.05). Interleukin-6 (IL-6) production did not differ between groups. Interestingly, tumor necrosis factor-alpha (TNF-α) was lower in animals receiving TTI. Our results corroborate the satietogenic effect of TTI in a MetS model. Furthermore, we showed that TTI added to a cafeteria diet may decrease inflammation regardless of weight loss. This puts TTI as a candidate for studies to test its effectiveness as an adjuvant in MetS treatment.
G protein-coupled receptors (GPCRs) are the most important targets for drug discovery and not surprisingly ∼40% of all drugs currently in the market act on these receptors. Currently, one of the most active areas in GPCRs signaling is biased agonism, a phenomenon that occurs when a given ligand is able to preferentially activate one (or some) of the possible signaling pathways. In this review, we highlight the most recent findings about biased agonism, including an extension of this concept to intracellular signaling, allosterism, strategies for assessment and interpretation, and perspectives of therapeutic applications for biased agonists.
Introduction: Five months after the first confirmed case of COVID-19 in Brazil, the country has the second highest number of cases in the world. Without any scientifically proven drug or vaccine available combined with COVID-19's high transmissivity, slowing down the spread of the infection is a challenge. In an attempt to save the economy, the Brazilian government is slowly beginning to allow nonessential services to reopen for in-person customers. Methods: In this study, we analyze, based on data analysis and statistics, how other countries evolve and under which conditions they decided to resume normal activity. In addition, due to the heterogeneity of Brazil, we explore Brazilian data of COVID-19 from the State Health Secretaries to evaluate the situation of the pandemic within the states. Results: Results show that while other countries have flattened their curves and present low numbers of active cases, Brazil continues to see an increase in COVID-19 patients. Furthermore, a number of important states are easing restrictions despite a high percentage of confirmed cases. Conclusions: All analyses show that Brazil is not ready for reopening, and the premature easing of restrictions may increase the number of COVID-19-related deaths and cause the collapse of the public health system.
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