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The actual VITamin Deborah along with OmegA-3 Test (Essential): Do Results Differ by simply Making love or even Race/Ethnicity?
The mouse metabolic LUMINEX assay proved unsuitable for quantitating glucagon, GLP-1, IL-6, and TNFα, due to undetectable levels in most fasting and non-fasting plasma. Overall, quantitative leptin levels were the only reliable data obtained from the mouse metabolic LUMINEX assay.COVID-19, emerged at the end of 2019 have dramatically threatened the health, economy, and social mobility of people around the world and till date no medication is available for its treatment. An amazing herb, Nigella sativa, having antiviral, antihypertensive, anti- diarrhoeal, analgesics, and anti-bacterial properties, needs to be explored for its efficacy against SARS-CoV-2, the causative agent of COVID-19. In-silico studies were carried out to understand the role of its bioactive constituents in COVID-19 treatment and prevention. Firstly, the disease network was prepared by using ACE2 (Angiotensin-II receptor), as it is the entry site for virus. It was used to decipher the mechanism of SARS-COV-2 infection in humans. Second, the target receptors for N. sativa were predicted and protein interaction studies were conducted. Further, docking studies were also performed to analyse it for treatment purpose as well. This study concludes that pathways undertaken by N. sativa bioactive constituents were similar to the pathways followed in SARS-COV-2 pathology, like renin-angiotensin system, kidney functions, regulation of blood circulation, blood vessel diameter, etc. Also, in docking studies, the constituents of N. sativa, α-hederin, Thymohydroquinone and Thymoquinone were observed to be efficiently binding to ACE2. Also, the bioactive phytoconstituents are involved in molecular pathways like HIF1, VEGF, IL-17, AGE-RAGE, chemokine and calcium signaling pathways which can be majorly helpful in combating hypoxia and inflammation caused due to compromised immune system and oxidative stress. Therefore, N. sativa standardized extract having the above phytoconstituents could be useful in COVID-19 and hence opens a new treatment line.The Center for Disease Control (CDC) recommended that direct support professionals (DSPs) take additional steps to protect people with disabilities during COVID-19 and receive training on the use of personal protective equipment and infection prevention. The Golisano Institute for Developmental Disability Nursing identified this as an unmet need and created an online asynchronous course for DSPs on infection prevention and use of personal protective equipment to reduce transmission of COVID-19 among individuals with disabilities and DSPs. Constructivism, experiential learning theory, and active learning theory guided content development. 4-Chloro-DL-phenylalanine The course used games to break-up dense information into more manageable chunks as a means to increase learner engagement and motivation. The course was delivered on a dynamic Learning Management System to allow for a variety of content authoring tools to be utilized. After evaluation, the course was disseminated to DSPs. Future directions include a broader infection protection course for DSPs, without a direct focus on COVID-19.Coronavirus Disease 2019 (COVID-19) has infected more than thirty five million people worldwide and caused nearly 1 million deaths as of October 2020. The microorganism causing COVID-19 was named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV). The aim of this study was to investigate the interactions of twenty-three phytochemicals belonging to different flavonoid subgroups with the receptor binding domain (RBD) of the spike glycoprotein of 2019-nCoV, and cellular proteases [transmembrane serine protease 2 (TMPRSS2), cathepsin B and L (CatB/L)]. The compounds interacted more strongly with CatB and CatL than with the other proteins. Van der Waals and hydrogen bonds played an important role in the receptor-ligand interactions. As a result of RBCI (relative binding capacity index) analysis conducted to rank flavonoids in terms of their interactions with the target proteins, (-)-epicatechin gallate interacted strongly with all the proteins studied. The results obtained from molecular dynamics and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) methods also supported this data. According to Lipinski's rule of five, (-)-epicatechin gallate showed drug-likeness properties. Although this molecule is not capable of crossing the blood-brain barrier (BBB), it was concluded that (-)-epicatechin gallate can be evaluated as a candidate molecule in drug development studies against 2019-nCoV since it was not the substrate of P-gp (P-glycoprotein), did not inhibit any of the cytochrome Ps, and did not show AMES toxicity or hepatotoxicity on eukaryotic cells.The p53 gene is mutated in greater than 50% of several human cancers including bladder urothelial carcinoma, lung adenocarcinoma, colorectal carcinoma, and oral cancer. Mutations in the p53 gene occur predominantly in the DNA-binding domain causing loss of function and accumulation of dysfunctional p53 protein in tumors by hetero-oligomerization with the wild type p53. Thus an in silico approach for the rational design of potent, pharmacologically active small drug-like compounds targeting mutated p53 was undertaken. Molecular dynamics simulations of the wild type p53 monomer and p53 mutants R175H and R248Q were performed using Discovery Studio v3.5. Phase was used to generate pharmacophore models and the sitemap generated pocket was used to screen the Maybridge HitFinderTM library using Schrodinger Suite. We identified ten compounds (Cmpd-1 to Cmpd-10) that showed preferential binding to p53 mutants, and their pharmacokinetic profiles complied with the ADMET rules. Cmpd-4 and Cmpd-8 demonstrated binding with mutated p53 at cysteine 124, similar to the mutant p53 reactivating compound APR-246 (PRIMA-1Met) for functional restoration of the mutant p53. We propose the identified compounds as suitable drug candidates against mutated p53 protein, with the specific small drug-like molecules as either single drugs or in combination with lower doses of additional cytotoxic drugs, consequently reducing adverse side effects in patients. Communicated by Ramaswamy H. Sarma.Introduction Vascular complications are the major cause of morbidity in patients with diabetes mellitus. Screening for these complications is crucial in early detection and tertiary prevention. Hence, this study aimed at finding the prevalence of micro and macrovascular complications and their associated factors in type 2 diabetes mellitus patients in a rural health center by using simple and easily available tools. Methodology This hospital based cross sectional study was conducted in Rural Health and Training Centre (RHTC) of Sri Ramachandra medical college from Jan 2017 to Aug 2017. All type 2 diabetes patients registered at RHTC were included in the study. By the use of questionnaire, clinical examination and laboratory investigations, the prevalence of macro and microvascular complications and associated factors were ascertained. Multiple logistic regression was used to identify factors associated with vascular complications of diabetes. Results The study included 390 type 2 diabetes patients. The overall prevalence of macrovascular and microvascular complications in our study population was 29.7% and 52.1%, respectively. Among the macrovascular complications, both coronary artery disease (CAD) and peripheral vascular disease (PVD) had a prevalence rate of 15.1%. Among the microvascular complications, peripheral neuropathy (44.9%) had the highest prevalence followed by nephropathy (12.1%) and diabetic foot (7.2%). Multiple logistic regression analyses showed high HbA1c level, lower education, high postprandial blood sugar, hypertension, abdominal obesity were significantly associated with increased risk of vascular complications of diabetes. Conclusion This study demonstrated the increased prevalence of vascular complications in Type 2 diabetes patients in rural India. Regular screening to identify those patients at risk could prevent further progression of complications.Dear Editor,I am writing to you in order to highlight some miscalculations in an article published in the journal of Technology in Cancer Research & Treatment, entitled; "SRS in Combination with Ipilimumab A Promising New Dimension for Treating Melanoma Brain Metastases" by Khan, et al.1 These miscalculations changed the derived conclusion about median survival time, and adverse effects in the selected treatment groups. So, amending these miscalculations may help readers in future research decisions.While an FDA approved drug Ivermectin was reported to dramatically reduce the cell line of SARS-CoV-2 by ∼5000 folds within 48 h, the precise mechanism of action and the COVID-19 molecular target involved in interaction with this in-vitro effective drug are unknown yet. Among 12 different COVID-19 targets along with Importin-α studied here, the RNA dependent RNA polymerase (RdRp) with RNA and Helicase NCB site show the strongest affinity to Ivermectin amounting -10.4 kcal/mol and -9.6 kcal/mol, respectively, followed by Importin-α with -9.0 kcal/mol. Molecular dynamics of corresponding protein-drug complexes reveals that the drug bound state of RdRp with RNA has better structural stability than the Helicase NCB site and Importin-α, with MM/PBSA free energy of -187.3 kJ/mol, almost twice that of Helicase (-94.6 kJ/mol) and even lower than that of Importin-α (-156.7 kJ/mol). The selectivity of Ivermectin to RdRp is triggered by a cooperative interaction of RNA-RdRp by ternary complex formation. Identification of the target and its interaction profile with Ivermectin can lead to more powerful drug designs for COVID-19 and experimental exploration.To confront a disease like Alzheimer's disease having complex pathogenesis, development of multitarget-directed ligands has emerged as a promising drug discovery approach. In our endeavor towards the development of multitarget-directed ligands for Alzheimer's disease, a series of indoloquinoxaline derivatives were designed and synthesized. In vitro cholinesterase inhibition studies revealed that all the synthesized compounds exhibited moderate to good cholinesterase inhibitory activity. 6-(6-(Piperidin-1-yl)hexyl)-6H-indolo[2,3-b]quinoxaline 9f was identified as the most potent and selective BuChE inhibitor (IC50 = 0.96 µM, selectivity index = 0.17) that possessed 2 fold higher BuChE inhibitory activity compared to the commercially approved reference drug donepezil (IC50 = 1.87 µM). Moreover, compound 9f is also endowed with self-induced Aβ1-42 aggregation inhibitory activity (51.24% inhibition at 50 μM concentration). Some of the compounds of the series also displayed moderate anti-oxidant activity. To perceive a putative binding mode of the compound 9f, molecular docking studies were carried out, and the results pointed out significant interactions of compound 9f with the enzymes in the binding sites of cholinesterases as well as Aβ1-42. Additionally, compound 9f exhibited favorable in silico ADMET properties. Put together these findings project compound 9f as a potential multitarget-directed ligand in the direction of developing novel anti-AD drugs. Communicated by Ramaswamy H. Sarma.
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