COVID19 ailment severeness evaluation using Nbc model

Background The role of free radical reactions in disease pathology is well known to be involved in many acute and chronic disorders in human beings, such as diabetes, atherosclerosis, aging, immunosuppression and neurodegeneration. The search for new drugs of plant origin becomes increasingly urgent due to drug resistance. Aloe schelpei is an endemic Aloe species traditionally used for the treatment of infectious and chronic diseases. Aim This study was conducted to evaluate free radical scavenging activities of leaf latex of Aloe schelpei and its isolated compounds. Methods The leaf latex of A. schelpei was subjected to preparative thin-layer chromatography to afford three compounds. Free radical scavenging activities of the leaf latex and its constituents was carried out using a 2, 2-diphenyl-1-picrylhydrazyl method. Results Phytochemical investigation of the leaf latex Aloe schelpei by prepartive thin layer chromatography led to the isolation of three compounds, identified as microdontin A/B (1), aloin A/B (2) and aloinoside A/B (3). The results showed that the leaf latex had a strong free radical scavenging activity reaching a maximum of 84.3% at a concentration of 100 μg/mL, and with an IC50 value of 25.3 ± 2.45 μg/mL (p less then 0.05). Among the isolated compounds, microdontin A/B (1) was found to have the strongest free radical scavenging activity with an IC50 value of 0.07 ± 0.005 mμ, followed by aloinoside A/B (IC50 = 0.13 ± 0.01 mM) and aloin A/B (IC50 = 0.15 ± 0.02 mM). Conclusion The traditional medicinal practice of the leaf latex may be due to the antioxidant activities of the leaf latex of A. schelpei and the isolated compounds. © 2020 Teka and Kassahun.Background Bisdemethoxycurcumin (BDMC), a stable bioactive ingredient in curcuminoids, is associated with various antitumor functions, such as proliferation inhibition, metastasis suppression and apoptosis induction, in many cancer types. However, the mechanism of BDMC in hepatocellular carcinoma (HCC) remains unclear. Methods We assessed the toxicity and the inhibitory effect of BDMC in the HepG2 cell line by using CCK-8 and colony formation assays. The regulatory effects of BDMC on Akt and MAPK signaling were investigated by Western blotting and immunoprecipitation. Results We found that the half-maximum inhibitory concentration (IC50) of BDMC after 48 hrs of treatment was 59.13 μM, and BDMC inhibited proliferation in a time- and dose-dependent manner in HepG2 cells. The inhibitory effect was caused by the inactivation of Akt signaling, but not Erk, Jnk or p38 signaling. In addition, the inactivation of Akt signaling was attributed to the inhibition of ubiquitination mediated by K63-Ub but not K48-Ub. Furthermore, we found that BDMC upregulated the expression of CYLD, leading to Akt deubiquitination and inactivation. Conclusion BDMC inhibited HCC cell proliferation, and that this effect was induced by Akt inactivation via CYLD-mediated deubiquitination. GSK-4362676 ic50 © 2020 Qiu et al.Purpose This study aimed to synthesize twin drugs from cinnamic acid compounds, caffeic acid (CFA) and ferulic acid (FLA), which can antagonize endothelin-1 (ET-1) with telmisartan through ester bonds. Moreover, the antihypertensive effect of telmisartan and its influence on blood pressure variability (BPV) were enhanced, and the bioavailability of caffeic acid and ferulic acid was improved. Methods Six twin drugs, which were the target compounds, were synthesized. Hypertensive rats (SHR) and conscious sinoaortic-denervated (SAD) rats were spontaneously used as models for pharmacodynamic research to study the antihypertensive efficacy of these twin drugs. Wistar rats were employed as pharmacokinetic research models to investigate the pharmacokinetics of the target compounds via intragastric administration. Cellular pharmacodynamic research was also conducted on the antagonistic action on Ang II-AT1, ETA and ETB receptor. Results Compound 1a was determined as the best antihypertensive twin drug and thus was fuas a basis for the development of new angiotensin receptor blocker (ARB) in the future and a reference for the development of new drugs to antagonize ET-1. © 2020 Li et al.Purpose Annatto-derived tocotrienol (AnTT) has been shown to improve bone formation in animal models of osteoporosis and promote differentiation of pre-osteoblastic cells. However, the mechanism of action of AnTT in achieving these effects is unclear. This study aims to investigate the mechanism of action of AnTT on MC3T3-E1 pre-osteoblasts via the mevalonate pathway. Methods Murine pre-osteoblastic cells, MC3T3-E1, were cultured with the density of 1 × 104 cells/mL and treated with 4 concentrations of AnTT (0.001-1 µg/mL). Expression of HMG-CoA reductase (HMGR) gene was carried out using qPCR after treatment with AnTT for 21 days. RhoA activation and bone morphogenetic protein-2 (BMP-2) were measured using immunoassay after 9 and 15 days of AnTT treatment. Lovastatin was used as the positive control. Mineralized nodules were detected using Von Kossa staining after 21 days of AnTT treatment. Results The results showed that HMGR was up-regulated in the lovastatin group on day 9 and 21 compared to the control. Lovastatin also inhibited RhoA activation (day 9 and 15) and increased BMP-2 protein (day 15). On the other hand, AnTT at 0.001 μg/mL (day 3) and 0.1 μg/mL (day 21) significantly down-regulated HMGR gene expression compared to the control. On day 21, HMGR gene expression was significantly reduced in all groups compared to day 15. AnTT at 0.1 μg/mL significantly decreased RhoA activation on day 9 compared to the control. AnTT at 1 μg/mL significantly increased BMP-2 protein on day 15 compared to the control (P less then 0.05). Mineralized calcium nodules were more abundant in AnTT treated groups compared to the control on day 21. Conclusion AnTT suppresses the mevalonate pathway by downregulating HMGR gene expression and inhibiting RhoA activation, leading to increased BMP-2 protein in MC3T3-E1 cells. This explains the stimulating effects of AnTT on osteoblast mineralization. © 2020 Wan Hasan et al.Objective This study aimed to quantify the amount of perindopril and its active metabolite perindoprilat present in breast milk and corresponding maternal and infant plasma concentrations. Design Prospective, longitudinal, observational. Setting Tertiary specialist paediatric and obstetric hospital in Adelaide, South Australia. Population Breastfeeding women actively treated with perindopril for hypertensive disorders postpartum. Methods Eight breast milk samples and a single plasma sample were collected from each participant over a 24 hrs period, and plasma samples were taken from eligible breastfed infants. Breast milk and plasma concentrations of perindopril and perindoprilat were analysed using a validated Liquid Chromatography tandem-Mass Spectrometry (LC-MS/MS) method. Main Outcome Measures Mean breast milk concentrations of perindopril and perindoprilat, Relative Infant Dose (RID) less then 10%, and Theoretical Infant Dose (TID). Results Ten women and three infants participated in the study. The mean concentration of perindopril in breast milk for each participant ranged from 0.