Martingade3707

Introduction RIP1 kinase is a serine/threonine-protein kinase that has recently emerged as a central regulator of TNF-α dependent programmed necrosis (necroptosis), an inflammatory form of cell death, with important roles in inflammation and neurodegeneration. Small molecule RIP1 kinase inhibitors may provide new opportunities for treating a variety of autoimmune, inflammatory, and neurodegenerative diseases, among others, and thus have attracted widespread drug development efforts and a corresponding large amount of patent activity in recent years. Areas covered This review focuses on the patent literature covering small molecule inhibitors of RIP1 kinase from 2016-present. Expert opinion Inhibition of programmed necrosis (necroptosis) by RIP1 kinase inhibitors is a new field that has attracted widespread recent interest as a possible therapeutic means to treat a number of diseases in the inflammatory, neurodegenerative, and oncology areas. The interest in the therapeutic potential of RIP1kinase is evidenced by more than 40 small molecule patent applications published since 2016. To date, only a few RIP1 kinase inhibitors have entered the clinic. An understanding of the optimal clinical setting, in terms of dosing and disease indications for RIP1 inhibition, will require further clinical readouts as the current inhibitors progress and additional molecules enter into full development.Lutein, a potent antioxidant and the main macular pigment that protects the macula from light-initiated oxidative damage, has low bioavailability. Various nanoscale delivery systems have been developed for improving its bioavailability. This systematic review aims to evaluate the effectiveness of nanoscale delivery systems on improving lutein bioavailability in rodent models. Using EBSCOhost and PubMed, a total of eleven peer-reviewed articles published from 2000 to 2020 were identified. Plasma lutein concentration, pharmacokinetic parameters, including maximum concentration (Cmax), area under curve (AUC), and time to reach the maximum concentration (Tmax), and lutein accumulation in organs were extracted to evaluate the bioavailability of lutein using nanoscale delivery methods as compared with unencapsulated or raw lutein. Various nanoscale delivery systems, including polymer nanoparticles, emulsions, and lutein nanoparticles, significantly improved the bioavailability of lutein, as evidenced by increased plasma lutein concentrations, Cmax, or AUC. Additionally, five out of seven studies observed enhanced accumulation of lutein in the liver and the eyes. Polymer nanoparticles and emulsions improve the dispersibility and stability of lutein, thus lutein might be more accessible in the small intestine. Lutein nanoparticles shortened the Tmax. Further studies are warranted to evaluate the effectiveness of nanoscale delivery systems on improving the functionalities of lutein.The gut microbiome comprises a variety of microorganisms whose genes encode proteins to carry out crucial metabolic functions that are responsible for the majority of health-related issues in human beings. The advent of the technological revolution in artificial intelligence (AI) assisted synthetic biology (SB) approaches will play a vital role in the modulating the therapeutic and nutritive potential of probiotics. This can turn human gut as a reservoir of beneficial bacterial colonies having an immense role in immunity, digestion, brain function, and other health benefits. Hence, in the present review, we have discussed the role of several gene editing tools and approaches in synthetic biology that have equipped us with novel tools like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR-Cas) systems to precisely engineer probiotics for diagnostic, therapeutic and nutritive value. A brief discussion over the AI techniques to understand the metagenomic data from the healthy and diseased gut microbiome is also presented. Further, the role of AI in potentially impacting the pace of developments in SB and its current challenges is also discussed. The review also describes the health benefits conferred by engineered microbes through the production of biochemicals, nutraceuticals, drugs or biotherapeutics molecules etc. Finally, the review concludes with the challenges and regulatory concerns in adopting synthetic biology engineered microbes for clinical applications. Bucladesine chemical structure Thus, the review presents a synergistic approach of AI and SB toward human gut microbiome for better health which will provide interesting clues to researchers working in the area of rapidly evolving food and nutrition science.Several studies show an association of maternal diabetes during pregnancy with adverse offspring metabolic health. Other studies, however, suggest that this effect might be biased by obesity, which is independently associated with offspring metabolic disease and often coexistent to maternal diabetes. We performed a prospective study in a rat model to test the hypothesis that the burden of a diabetic pregnancy without obesity deteriorates metabolic health in male offspring. We generated maternal type 2 diabetes before conception that persisted during pregnancy by knockdown of the insulin receptor in small hairpin RNA-expressing transgenic rats. Male WT (wild type) offspring were followed up until adulthood and metabolically challenged by high-fat diet. Blood glucose was measured continuously via a telemetry device. Glucose and insulin tolerance tests were performed, and body composition was analyzed. Weight gain and glucose levels during adolescence and adulthood were similar in male offspring of diabetic and control pregnancies. Body weight and fat mass after high-fat diet, as well as glucose and insulin tolerance tests, were unaltered between male adult offspring of both groups. Glycemic control consisting of up to 49 000 individual glucose measures was comparable between both groups. Intrauterine exposure to maternal hyperglycemia and hyperinsulinemia without obesity had no impact on male offspring metabolic health in our model. We conclude that the intrauterine exposure itself does not represent a mechanism for fetal programming of diabetes and obesity in our model. Other maternal metabolic parameters during pregnancy, such as obesity, might impact long-term offspring metabolic health.