• Swain Stevenson posted an update 6 days, 9 hours ago

    In this opinion article, we conjecture a dialogue by the figure of Sérgio Ferreira which brought together basic science of classical pharmacology and clinical repercussions in COVID-19, then we propose that in the course of SARS-CoV-2 infection i) downregulation of ACE2 impairs the angiotensin II and DABK inactivation; ii) BK and its metabolite DABK seems to be in elevated levels in tissues by interferences in kallikrein/kinin system; iii) BK1 receptor contributes to the outbreak and maintenance of the inflammatory response; iv) kallikrein/kinin system crosstalks to RAS and coagulation system, linking inflammation to thrombosis and organ injury. We hypothesize that targeting the kallikrein/kinin system and BKB1R pathway may be beneficial in SARS-CoV-2 infection, especially on early stages. Apalutamide chemical structure This route of inference should be experimentally verified by SARS-CoV-2 infected mice.In this paper, we introduce an integrated, portable, affordable and simple to use heart rate variability (HRV) analysis tool STREME. The system consists of an ECG acquisition device and software for HRV analysis. We assessed the reliability and validity of using STREME against the reference standards RMS VarioWin and Kubios HRV for the short term HRV analysis. The validation study was carried out with the participation of 46 healthy subjects that included 15 men and 31 women with an average age of 27.67 ± 7.75yrs. The results showed that there is a significantly strong correlation (r > 0.95, p less then 0.001) between STREME and reference systems in HRV indices. The Bland-Altman analysis of all features computed from STREME and reference system represent a close agreement for all the parameters. Hence STREME HRV analysis tool can be recommended to researchers and other professionals for the evaluation of autonomic function using short term HRV.COVID-19, a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread across the globe. Predisposing factors such as age, diabetes, cardiovascular disease, and lowered immune function increase the risk of disease severity. T cell exhaustion, high viral load, and high levels of TNF-ɑ, IL1β, IL6, IL10 have been associated with severe SARS-CoV-2. Cytokine and antigen overstimulation are potentially responsible for poor humoral response to the virus. Lower cellular redox status, which leads to pro-inflammatory states mediated by TNF-ɑ is also potentially implicated. In vivo, in vitro, and human clinical trials have demonstrated N-acetylcysteine (NAC) as an effective method of improving redox status, especially when under oxidative stress. In human clinical trials, NAC has been used to replenish glutathione stores and increase the proliferative response of T cells. NAC has also been shown to inhibit the NLRP3 inflammasome pathway (IL1β and IL18) in vitro, and decrease plasma TNF-ɑ in human clinical trials. Mediation of the viral load could occur through NAC’s ability to increase cellular redox status via maximizing the rate limiting step of glutathione synthesis, and thereby potentially decreasing the effects of virally induced oxidative stress and cell death. We hypothesize that NAC could act as a potential therapeutic agent in the treatment of COVID-19 through a variety of potential mechanisms, including increasing glutathione, improving T cell response, and modulating inflammation. In this article, we present evidence to support the use of NAC as a potential therapeutic agent in the treatment of COVID-19.MEF2D-fusion (M-fusion) genes are newly discovered recurrent gene abnormalities that are detected in approximately 5 % of acute lymphoblastic leukemia (ALL) cases. Their introduction to cells has been reported to transform cell lines or increase the colony formation of bone marrow cells, suggesting their survival-supporting ability, which prompted us to examine M-fusion-targeting drugs. To identify compounds that reduce the protein expression level of MEF2D, we developed a high-throughput screening system using 293T cells stably expressing a fusion protein of MEF2D and luciferase, in which the protein expression level of MEF2D was easily measured by a luciferase assay. We screened 3766 compounds with known pharmaceutical activities using this system and selected staurosporine as a potential inducer of the proteolysis of MEF2D. Staurosporine induced the proteolysis of M-fusion proteins in M-fusion (+) ALL cell lines. Proteolysis was inhibited by caspase inhibitors, not proteasome inhibitors, suggesting caspase dependency. Consistent with this result, the growth inhibitory effects of staurosporine were stronger in M-fusion (+) ALL cell lines than in negative cell lines, and caspase inhibitors blocked apoptosis induced by staurosporine. We identified the cleavage site of MEF2D-HNRNPUL1 by caspases and confirmed that its caspase cleavage-resistant mutant was resistant to staurosporine-induced proteolysis. Based on these results, we investigated another Food and Drug Administration-approved caspase activator, venetoclax, and found that it exerted similar effects to staurosporine, namely, the proteolysis of M-fusion proteins and strong growth inhibitory effects in M-fusion (+) ALL cell lines. The present study provides novel insights into drug screening strategies and the clinical indications of venetoclax.Recent evidence indicates the use of probiotics in the prevention and treatment of diseases. Probiotics are capable of changing the gut microbiota composition and bile acid synthesis to elicit health benefits such as cholesterol-lowering, weight reduction, and improving insulin sensitivity. The aging population is prone to develop diseases because of their decreased physiological and biological systems. Probiotics are one of the promising supplements that may potentially counteract these detrimental effects. This review will discuss the influence of probiotics on bile acids in different populations-the elderly, obese individuals, and those with hypercholesterolemia, type 2 diabetes, hypertension, and non-alcoholic fatty liver disease.Flower of Gentiana veitchiorum has traditionally been used as an herbal medicine in Tibet for treatment of variola, respiratory infection, and pneumonia. However, the effective components contained in flower are not identified yet, and the underlying mechanisms for anti-inflammatory, antibacterial, and antioxidative activities remain to be elucidated. Here, we first extracted the flavonoid mixture from G. veitchiorum flower. The mixture was then further isolated and the within compounds was identified through the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The results showed that apigenin (4′,5,7-trihydroxyflavone) was the most abundant flavonoid in G. veitchiorum flower. We next examined the antioxidative activity of the extracted apigenin using the ferric reducing/antioxidant power (FRAP), the 1,1-diphenyl-2-picrylhydrazyl (DPPH), and the 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) assays and found that a positive correlation between apigenin concentration and reactive oxygen species (ROS) scavenging rate.