identification of RBD subdomain of spike protein from Pro-Thr for applications in vaccine development against SARS-CoV2.

The three-dimensional hybrid structures of coronavirus spike proteins including the C-terminal sequence and receptor binding motif (RBM) was remodeled and energy minimized. Further, protein-protein docking show that Receptor Binding Domain (RBD) of SARS-CoV 2 Lys-Pro bind on the surface of ACE2 receptor near N-terminal helices to form host-pathogen attachment. In this binding interface, SARS-CoV 2 shows a tight network of hydrogen bonds than other spike proteins from BtRsRaTG13-CoV, SARS-CoV, BtRsBeta-CoV, BtRsCoV-related, Pangolin-CoV (PCoV), human-CoV (hCoV), MERS-CoV (MCoV), Avian-CoV (ACoV) and PEDV1-CoV.

Role of c-Jun-N-Terminal Kinase in Pregnane X Receptor-Mediated Induction of Human Cytochrome P4503A4 In Vitro.

Cytochrome P450 CYP3A4 is the most abundant drug-metabolizing enzyme and is responsible for the metabolism of ∼50% of clinically available drugs. Induction of CYP3A4 impacts the disposition of its substrates and leads to harmful clinical consequences, such as failure of therapy. To prevent such undesirable consequences, the molecular mechanisms of regulation of CYP3A4 need to be fully understood.

Quercetin attenuates the hyperoxic lung injury in neonatal mice: Implications for Bronchopulmonary dysplasia (BPD).

Quercetin (QU) is one of the most common flavonoids that are present in a wide variety of fruits, vegetables, and beverages. This compound possesses potent anti-inflammatory and anti-oxidant properties. Supplemental oxygen is routinely administered to premature infants with pulmonary insufficiency.

Mast Cell-Dependent CD8 T-cell Recruitment Mediates Immune Surveillance of Intestinal Tumors in Apc Mice.

The presence of mast cells in some human colorectal cancers is a positive prognostic factor, but the basis for this association is incompletely understood. Here, we found that mice with a heterozygous mutation in the displayed reduced intestinal tumor burdens and increased survival in a chemokine decoy receptor, ACKR2-null background, which led to discovery of a critical role for mast cells in tumor defense. ACKR2Apc tumors showed increased infiltration of mast cells, their survival advantage was lost in mast cell-deficient ACKR2SAApc mice as the tumors grew rapidly, and adoptive transfer of mast cells restored control of tumor growth.

Leukotriene B-receptor-1 mediated host response shapes gut microbiota and controls colon tumor progression.

Inflammation and infection are key promoters of colon cancer but the molecular interplay between these events is largely unknown. Mice deficient in leukotriene B receptor1 (BLT1) are protected in inflammatory disease models of arthritis, asthma and atherosclerosis. In this study, we show that BLT1 mice when bred onto a spontaneous tumor (Apc) model displayed an increase in the rate of intestinal tumor development and mortality.

Association between alcohol-induced oxidative stress and membrane properties in synaptosomes: A protective role of vitamin E.

Chronic and excessive alcohol consumption leads to various neurological diseases. Synaptosomes are ideal organelles to study the functional properties of the brain in alcoholism. This study focuses on the association between oxidative stress and synaptosomal membrane properties in alcohol treated rats.

Role of Cyclooxygenase-2 Pathway in Creating an Immunosuppressive Microenvironment and in Initiation and Progression of Wilms' Tumor.

Wilms' tumors (WT), which accountfor 6% of all childhood cancers, arise from dysregulated differentiation of nephrogenic progenitor cells from embryonic kidneys. Though there is an improvement in the prognosis of WT, still 10% of patients with WT die due to recurrence. Thus more effective treatment approaches are necessary.

Newborn Mice Lacking the Gene for Cyp1a1 Are More Susceptible to Oxygen-Mediated Lung Injury, and Are Rescued by Postnatal β-Naphthoflavone Administration: Implications for Bronchopulmonary Dysplasia in Premature Infants.

Prolonged hyperoxia contributes to bronchopulmonary dysplasia (BPD) in preterm infants. β-Naphthoflavone (BNF) is a potent inducer of cytochrome P450 (CYP)1A enzymes, which have been implicated in hyperoxic injuries in adult mice. In this investigation, we tested the hypothesis that newborn mice lacking the Cyp1a1 gene would be more susceptible to hyperoxic lung injury than wild-type (WT) mice and that postnatal BNF treatment would rescue this phenotype by mechanisms involving CYP1A and/or NAD(P)H quinone oxidoreductase (NQO1) enzymes.

Association between alcohol-induced erythrocyte membrane alterations and hemolysis in chronic alcoholics.

The present study aimed to understand the association between erythrocyte membrane alterations and hemolysis in chronic alcoholics. Study was conducted on human male volunteers aged between 35-45 years with a drinking history of 8-10 years. Results showed that plasma marker enzymes AST, ALT, ALP and γGT were increased in alcoholic subjects.

Omeprazole induces heme oxygenase-1 in fetal human pulmonary microvascular endothelial cells via hydrogen peroxide-independent Nrf2 signaling pathway.

Omeprazole (OM) is an aryl hydrocarbon receptor (AhR) agonist and a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Recently, we showed that OM induces NAD (P) H quinone oxidoreductase-1 (NQO1) via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent mechanism. Heme oxygenase-1 (HO-1) is another cytoprotective and antioxidant enzyme that is regulated by Nrf2.

Modulatory role of Pterocarpus santalinus against alcohol-induced liver oxidative/nitrosative damage in rats.

Pterocarpus santalinus, a traditional medicinal plant has shown protective mechanisms against various complications. The aim of the present study is to evaluate therapeutic efficacy of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced oxidative/nitrosative stress leading to hepatotoxicity.

Leflunomide Induces Pulmonary and Hepatic CYP1A Enzymes via Aryl Hydrocarbon Receptor.

Emerging evidence indicates that the aryl hydrocarbon receptor (AhR) plays a crucial role in normal physiologic homeostasis. Additionally, aberrant AhR signaling leads to several pathologic states in the lung and liver. Activation of AhR transcriptionally induces phase I (CYP1A) detoxifying enzymes.

Characterization of the inflammatory microenvironment and identification of potential therapeutic targets in wilms tumors.

The role of inflammation in cancer has been reported in various adult malignant neoplasms. By contrast, its role in pediatric tumors has not been as well studied. In this study, we have identified and characterized the infiltration of various inflammatory immune cells as well as inflammatory markers in Wilms tumor (WT), the most common renal malignancy in children.

Increased susceptibility to hyperoxic lung injury and alveolar simplification in newborn rats by prenatal administration of benzo[a]pyrene.

Maternal smoking is one of the risk factors for preterm birth and for the development of bronchopulmonary dysplasia (BPD). In this study, we tested the hypothesis that prenatal exposure of rats to benzo[a]pyrene (BP), a component of cigarette smoke, will result in increased susceptibility of newborns to oxygen-mediated lung injury and alveolar simplification, and that cytochrome P450 (CYP)1A and 1B1 enzymes and oxidative stress mechanistically contribute to this phenomenon. Timed pregnant Fisher 344 rats were administered BP (25 mg/kg) or the vehicle corn oil (CO) on gestational days 18, 19 and 20, and newborn rats were either maintained in room air or exposed to hyperoxia (85% O2) for 7 or 14 days.

Alcohol-induced oxidative stress in rat liver microsomes: Protective effect of Emblica officinalis.

The protective effect of Emblica officinalis fruit extract (EFE) against alcohol-induced oxidative damage in liver microsomes was investigated in rats. EFE (250mg/kg b.wt/day) and alcohol (5g/kg b.

Modification of erythrocyte membrane proteins, enzymes and transport mechanisms in chronic alcoholics: an in vivo and in vitro study.

Aim: The aim of the study was to elucidate the molecular mechanisms underlying the alcohol perturbation leading to deleterious effects on erythrocyte membrane transport in chronic alcoholics.

Methods: Membrane bound enzyme activities such as Na(+), K(+)-ATPase, Ca(2+),Mg(2+)-ATPase and acetylcholine esterase and membrane transport analysis by in vitro and erythrocyte membrane profile analysis in controls and chronic alcoholic red cells were analyzed.

Results: It was observed that decreased Na(+), K(+)-ATPase enzyme activity and increased activities of Ca(2+),Mg(2+)-ATPase and acetylcholine esterase in chronic alcoholics compared to controls.

Adaptive changes in fatty acid profile of erythrocyte membrane in relation to plasma and red cell metabolic changes in chronic alcoholic men.

Chronic alcohol consumption is a major reason for several human diseases, and alcoholism has been associated with a variety of societal problems. Changes in fatty acid metabolism in alcoholics and its effects leading to membrane damage are largely unknown. Therefore, we aimed to investigate the fatty acid composition of erythrocyte membrane phospholipids in relation with plasma lipid profile and other plasma metabolites in chronic alcoholics in comparison with controls.

Ethanol induced adaptive changes in blood for the pathological and toxicological effects of chronic ethanol consumption in humans.

Alcohol consumption is associated with a number of toxicological changes in blood and the oxidant-antioxidant system. The present study was performed to investigate the alcohol induced toxicological, pathological changes in blood and an adaptive role of erythrocyte antioxidant system in chronic alcoholics. Human male volunteers aged 44±6 years with similar dietary habits were divided into two groups, namely non-alcoholic controls and chronic alcoholics.

Chronic cigarette smoking alters erythrocyte membrane lipid composition and properties in male human volunteers.

Cigarette smoking is a major lifestyle factor influencing the health of human beings. The present study investigates smoking induced alterations on the erythrocyte membrane lipid composition, fluidity and the role of nitric oxide. Thirty experimental and control subjects (age 35+/-8) were selected for the study.

Smoking-induced alterations in platelet membrane fluidity and Na(+)/K(+)-ATPase activity in chronic cigarette smokers.

Aim: Cigarette smoking is a recognized risk factor for cardiovascular diseases and has been implicated in the pathogenesis of atherosclerosis. Platelet adhesiveness and aggregation increases as a result of smoking. Cigarette smoking modifies haemostatic parameters via thrombosis with a consequently higher rate of cardiovascular events, but smoking-induced alterations of platelet membrane fluidity and other changes have not been studied.

Alterations in erythrocyte membrane fluidity and Na+/K+ -ATPase activity in chronic alcoholics.

Ethanol disorders biological membranes causing perturbations in the bilayer and also by altering the physicochemical properties of membrane lipids. But, chronic alcohol consumption also increases nitric oxide (NO) production. There was no systemic study was done related to alcohol-induced production of NO and consequent formation of peroxynitrite mediated changes in biophysical and biochemical properties, structure, composition, integrity and function of erythrocyte membranes in chronic alcoholics.