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1.
Mol Divers ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39083218

RESUMO

Synthesis of functionalized chromenyl phosphonates by the reaction among 2-hydorxybenzaldehydes, dicyanoethane, and dialkyl phosphonates that was promoted by choline hydroxide ionic liquid catalyzes the simultaneous, Knoevenagel, Pinner, and phospha-Michael reactions, under neat condition at room temperature. Important phosphorus-containing compounds can be produced at a reasonable cost because of the mild reaction conditions and the inexpensive promoter choline hydroxide. Furthermore, the desired products can be obtained without the need for any extraction or chromatography steps. An alternate technique for the simple and high-yield synthesis of functionalized chromenyl phosphonates is offered by this protocol. The synthesized compounds were studied by anti-microbial activity and docking studies. The title compounds molecular docking investigations demonstrated their efficacy as therapeutic agents against DNA Gyrase B and Aspergillus niger endoglucanase in both antibacterial and antifungal inhibition, and they identified compounds 4a, 4d, 4l, 4p, and 4q as promising candidates for microbial treatment, with binding affinities ranging from - 6.9 to - 7.4 kcal/mol.

2.
Curr Issues Mol Biol ; 46(1): 106-120, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38248311

RESUMO

There are numerous clinically proven methods for treating cancer worldwide. Immunotherapy has been used to treat cancer with significant success in the current studies. The purpose of this work is to identify somatically altered target gene neoantigens and investigate liver cancer-related immune cell interaction and functional changes for potential immunotherapy in future clinical trials. Clinical patient data from the Cancer Genome Atlas (TCGA) database were used in this investigation. The R maf utility package was used to perform somatic analysis. The 17-mer peptide neoantigens were extracted using an in-house Python software called Peptide.py. Additionally, the epitope analysis was conducted using NetMHCpan4.1 program. Neopeptide immunogenicity was assessed using DeepCNN-Ineo, and tumor immune interaction, association with immune cells, correlation, and survival analysis were assessed using the TIMER web server. Based on somatic mutation analysis, we have identified the top 10 driver genes (TP53, TNN, CTNNB1, MUC16, ALB, PCLO, MUC4, ABCA13, APOB, and RYR2). From the superfamily of 20 HLA (Human leukocyte antigens) allele epitopes, we discovered 5653 neopeptides. Based on T cell receptor face hydrophobic analysis, these neopeptides were subjected to immunogenicity investigation. A mutation linked to tumor growth may have an impact on immune cells. According to this study's correlation and survival analysis, all driver genes may function as immune targets for liver cancer. These genes are recognized to be immune targets. In the future, immune checkpoint inhibitors may be developed to prolong patient survival times and prevent hepatocellular carcinoma (HCC) through immunotherapy.

3.
Crit Rev Biotechnol ; 41(3): 370-393, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33550862

RESUMO

Generally, plant growth, development, and their productivity are mainly affected by their growth rate and also depend on environmental factors such as temperature, pH, humidity, and light. The interaction between plants and pathogens are highly specific. Such specificity is well characterized by plants and pathogenic microbes in the form of a molecular signature such as pattern-recognition receptors (PRRs) and microbes-associated molecular patterns (MAMPs), which in turn trigger systemic acquired immunity in plants. A number of Arabidopsis mutant collections are available to investigate molecular and physiological changes in plants under the presence of different light conditions. Over the past decade(s), several studies have been performed by selecting Arabidopsis thaliana under the influence of red, green, blue, far/far-red, and white light. However, only few phenotypic and molecular based studies represent the modulatory effects in plants under the influence of green and blue lights. Apart from this, red light (RL) actively participates in defense mechanisms against several pathogenic infections. This evolutionary pattern of light sensitizes the pathologist to analyze a series of events in plants during various stress conditions of the natural and/or the artificial environment. This review scrutinizes the literature where red, blue, white, and green light (GL) act as sensory systems that affects physiological parameters in plants. Generally, white and RL are responsible for regulating various defense mechanisms, but, GL also participates in this process with a robust impact! In addition to this, we also focus on the activation of signaling pathways (salicylic acid and jasmonic acid) and their influence on plant immune systems against phytopathogen(s).


Assuntos
Arabidopsis , Microbiota , Arabidopsis/genética , Imunidade Vegetal , Ácido Salicílico , Transdução de Sinais
4.
Arch Microbiol ; 204(1): 8, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873656

RESUMO

Viral outbreaks had been a threat for the human race for a long time. Several epidemics and pandemics have been reported in the past with serious consequences on human health and subsequent social and economic aspects. According to WHO, viral infections continue to be a major health concern globally. Novel coronavirus, SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) causes the most recent infectious pandemic disease, COVID-19 (Coronavirus disease-19). As of now, there were 249 million infections of COVID-19 worldwide with a high mortality of more than 5 million deaths reported; and the number of new additional cases is drastically increasing. Development of therapies to treat the infected cases and prophylactic agents including vaccines that are effective towards different variants are crucial to curtail the COVID-19 pandemic. Owing to the fact that there is a high mortality and morbidity rate along with the risk of virus causing further epidemic outbursts, development of additional effective therapeutic and preventive strategies are highly warranted. Prevention, early detection and treatment will reduce the spread of COVID-19 pandemic. The present review highlights the novel mutations and therapeutic updates associated with coronaviruses along with the clinical manifestations-diagnosis, clinical management and, prophylactic and therapeutic strategies of COVID-19 infection.


Assuntos
COVID-19 , Vacinas , Humanos , Mutação , Pandemias , SARS-CoV-2
5.
Toxicol Mech Methods ; 30(9): 679-686, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32811246

RESUMO

The present study is an attempt to check the protective effect of fresh wheatgrass juice (WJ) as a potential therapeutic agent against alcohol-induced oxidative/nitrosative stress leading to nephrotoxicity in rats. Administration of 20% ethanol (5 g/kg b.wt/day) for 60 days resulted in a significant rise in the plasma concentrations of urea and creatinine with decreased levels of uric acid. Besides, a significant decrease in plasma electrolyte/mineral levels along with decreased activity of Na+/K+-ATPase activity was recorded in alcohol administered rats. In alcohol administered rats augmented lipid peroxidation (thio-barbituric acid reactive substance - TBARS) and nitric oxide (NOx) reflects the increased oxidative stress and nitrosative stress, moreover, we noticed a concomitant decrease in the levels of reduced glutathione (GSH) with decreased activities of antioxidant enzyme machinery viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione s-transferase (GST). Administration of WJ to the alcoholic rats significantly restored the plasma biochemical markers and the kidney antioxidant status near to control group animal levels. These findings were further confirmed by the kidney histopathological studies, wherein the protective effect of WJ treatment in retaining the morphological features of the renal tissue in spite of the alcohol administration was evident. The rich repertoire of phenolic compounds present in the WJ from the freshly sprouted seeds synergistically protected the kidney from alcohol-induced damage.


Assuntos
Antioxidantes/farmacologia , Etanol/toxicidade , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Triticum , Animais , Antioxidantes/isolamento & purificação , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Nitrosativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismo , Triticum/química
6.
J Clin Biochem Nutr ; 60(1): 63-69, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28163384

RESUMO

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. Plasma and erythrocyte membrane lipid peroxidation, erythrocyte lysate nitric oxide (NOx) levels were also increased significantly in alcoholics. Furthermore, erythrocyte membrane protein carbonyls, total cholesterol, phospholipid and cholesterol/phospholipid (C/P) ratio were increased in alcoholics. SDS-PAGE analysis of erythrocyte membrane proteins revealed that increased density of band 3, protein 4.2, 4.9, actin and glycophorins, whereas glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and glycophorin A showed slight increase, however, decreased ankyrin with no change in spectrins (α and ß) and protein 4.1 densities were observed in alcoholics. Moreover, alcoholics red blood cells showed altered morphology with decreased resistance to osmotic hemolysis. Increased hemolysis showed strong positive association with lipid peroxidation (r = 0.703, p<0.05), protein carbonyls (r = 0.754, p<0.05), lysate NOx (r = 0.654, p<0.05) and weak association with C/P ratio (r = 0.240, p<0.05). Bottom line, increased lipid and protein oxidation, altered membrane C/P ratio and membrane cytoskeletal protein profile might be responsible for the increased hemolysis in alcoholics.

7.
Proc Natl Acad Sci U S A ; 110(19): E1788-96, 2013 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-23610397

RESUMO

Breathing and blood pressure are under constant homeostatic regulation to maintain optimal oxygen delivery to the tissues. Chemosensory reflexes initiated by the carotid body and catecholamine secretion from the adrenal medulla are the principal mechanisms for maintaining respiratory and cardiovascular homeostasis; however, the underlying molecular mechanisms are not known. Here, we report that balanced activity of hypoxia-inducible factor-1 (HIF-1) and HIF-2 is critical for oxygen sensing by the carotid body and adrenal medulla, and for their control of cardio-respiratory function. In Hif2α(+/-) mice, partial HIF-2α deficiency increased levels of HIF-1α and NADPH oxidase 2, leading to an oxidized intracellular redox state, exaggerated hypoxic sensitivity, and cardio-respiratory abnormalities, which were reversed by treatment with a HIF-1α inhibitor or a superoxide anion scavenger. Conversely, in Hif1α(+/-) mice, partial HIF-1α deficiency increased levels of HIF-2α and superoxide dismutase 2, leading to a reduced intracellular redox state, blunted oxygen sensing, and impaired carotid body and ventilatory responses to chronic hypoxia, which were corrected by treatment with a HIF-2α inhibitor. None of the abnormalities observed in Hif1α(+/-) mice or Hif2α(+/-) mice were observed in Hif1α(+/-);Hif2α(+/-) mice. These observations demonstrate that redox balance, which is determined by mutual antagonism between HIF-α isoforms, establishes the set point for hypoxic sensing by the carotid body and adrenal medulla, and is required for maintenance of cardio-respiratory homeostasis.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Corpo Carotídeo/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Oxigênio/metabolismo , Medula Suprarrenal/fisiologia , Animais , Pressão Sanguínea , Sistema Cardiovascular , Corpo Carotídeo/metabolismo , Catecolaminas/metabolismo , Heterozigoto , Homeostase , Hipóxia , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , NADPH Oxidase 2 , NADPH Oxidases/metabolismo , Oxirredução , Células PC12 , Ratos , Superóxido Dismutase/metabolismo
8.
Proc Natl Acad Sci U S A ; 109(7): 2515-20, 2012 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-22232674

RESUMO

Recurrent apnea with intermittent hypoxia is a major clinical problem in preterm infants. Recent studies, although limited, showed that adults who were born preterm exhibit increased incidence of sleep-disordered breathing and hypertension, suggesting that apnea of prematurity predisposes to autonomic dysfunction in adulthood. Here, we demonstrate that adult rats that were exposed to intermittent hypoxia as neonates exhibit exaggerated responses to hypoxia by the carotid body and adrenal chromaffin cells, which regulate cardio-respiratory function, resulting in irregular breathing with apneas and hypertension. The enhanced hypoxic sensitivity was associated with elevated oxidative stress, decreased expression of genes encoding antioxidant enzymes, and increased expression of pro-oxidant enzymes. Decreased expression of the Sod2 gene, which encodes the antioxidant enzyme superoxide dismutase 2, was associated with DNA hypermethylation of a single CpG dinucleotide close to the transcription start site. Treating neonatal rats with decitabine, an inhibitor of DNA methylation, during intermittent hypoxia exposure prevented oxidative stress, enhanced hypoxic sensitivity, and autonomic dysfunction. These findings implicate a hitherto uncharacterized role for DNA methylation in mediating neonatal programming of hypoxic sensitivity and the ensuing autonomic dysfunction in adulthood.


Assuntos
Epigênese Genética , Coração/fisiologia , Homeostase , Hipóxia/fisiopatologia , Pulmão/fisiologia , Animais , Animais Recém-Nascidos , Ilhas de CpG , Metilação de DNA , Ratos
9.
Indian J Clin Biochem ; 30(2): 204-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25883430

RESUMO

The present study was designed to understand the cigarette smoking-induced alterations in hormones and the resulting changes in platelet serotonin (5-hydroxytryptamine, 5-HT) and monoamine oxidase (MAO-B) activity in chronic smokers. Human male volunteers aged 35 ± 8 years, were divided into two groups, namely controls and smokers (12 ± 2 cigarettes per day for 7-10 years). Results showed that cigarette smoking significantly (p < 0.05) elevated plasma triiodothyronine (T3), cortisol and testosterone levels with significant (p < 0.05) reduction in plasma tryptophan and thyroxin (T4). Moreover, smokers showed reduced platelet 5-HT levels and MAO-B activity. In smokers, plasma cortisol was negatively correlated with tryptophan (r = -0.386), platelet MAO-B (r = -0.264), and 5-HT (r = -0.671), and positively correlated with testosterone (r = 0.428). However, testosterone was negatively correlated with platelet MAO-B (r = -0.315), and 5-HT (r = -.419) in smokers. Further, smokers plasma T3 levels were negatively correlated with platelet MAO-B (r = -0.398), and 5-HT (r = -0.541), whereas T4 levels were positively correlated with platelet MAO-B (r = 0.369), and 5-HT (r = 0.454). In conclusion, our study showed that altered testosterone and cortisol levels may aggravate behavior, mood disturbances and symptoms of depression by decreasing platelet 5-HT and MAO-B activity in smokers.

10.
J Physiol ; 592(17): 3841-58, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24973414

RESUMO

Previous studies reported that chronic intermittent hypoxia (CIH) results in an imbalanced expression of hypoxia-inducible factor-α (HIF-α) isoforms and oxidative stress in rodents, which may be due either to the direct effect of CIH or indirectly via hitherto uncharacterized mechanism(s). As neural activity is a potent regulator of gene transcription, we hypothesized that carotid body (CB) neural activity contributes to CIH-induced HIF-α isoform expression and oxidative stress in the chemoreflex pathway. Experiments were performed on adult rats exposed to CIH for 10 days. Rats exposed to CIH exhibited: increased HIF-1α and decreased HIF-2α expression; increased NADPH oxidase 2 and decreased superoxide dismutase 2 expression; and oxidative stress in the nucleus tractus solitarius and rostral ventrolateral medulla as well as in the adrenal medulla (AM), a major end organ of the sympathetic nervous system. Selective ablation of the CB abolished these effects. In the AM, sympathetic activation by the CB chemoreflex mediates CIH-induced HIF-α isoform imbalance via muscarinic acetylcholine receptor-mediated Ca(2+) influx, and the resultant activation of mammalian target of rapamycin pathway and calpain proteases. Rats exposed to CIH presented with hypertension, elevated sympathetic activity and increased circulating catecholamines. Selective ablation of either the CB (afferent pathway) or sympathetic innervation to the AM (efferent pathway) abolished these effects. These observations uncover CB neural activity-dependent regulation of HIF-α isoforms and the redox state by CIH in the central and peripheral nervous systems associated with the chemoreflex.


Assuntos
Corpo Carotídeo/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/metabolismo , Estresse Oxidativo , Medula Suprarrenal/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Cálcio/metabolismo , Calpaína/metabolismo , Hipóxia/fisiopatologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Masculino , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ratos , Ratos Sprague-Dawley , Reflexo , Núcleo Solitário/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
11.
Pathophysiology ; 21(2): 153-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24393670

RESUMO

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.wt/day, 20%, w/v) were administered orally to animals for 60 days. Alcohol administration significantly increased lipid peroxidation, protein carbonyls with decreased sulfhydryl groups in microsomes, which were significantly restored to normal levels in EFE and alcohol co-administered rats. Alcohol administration also markedly decreased the levels of reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in the liver microsomes, which were prevented with EFE administration. Further, alcohol administration significantly increased the activities of cytochrome P-450, Na(+)/K(+) and Mg(2+) ATPases and also membrane fluidity. But, administration of EFE along with alcohol restored the all above enzyme activities and membrane fluidity to normal level. Thus, EFE showed protective effects against alcohol-induced oxidative damage by possibly reducing the rate of lipid peroxidation and restoring the various membrane bound and antioxidant enzyme activities to normal levels, and also by protecting the membrane integrity in rat liver microsomes. In conclusion, the polyphenolic compounds including flavonoid and tannoid compounds present in EFE might be playing a major role against alcohol-induced oxidative stress in rats.

12.
In Silico Pharmacol ; 12(1): 39, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721057

RESUMO

In the case of hepatocellular carcinoma, there is a need to find novel immune biomarkers to predict cancer prognosis, which will help prolong patient survival. On the basis of these findings, we explored the role of the hub genes in hepatocellular carcinoma via computational analysis for future immunotherapy. To study this phenomenon, we selected three datasets downloaded from the GEO database (GSE25097, GSE76427 and GSE84402). The gene expression analysis platform (GEAP) online tool was used for the data analysis to identify the DEGs. Functional enrichment analysis was performed by GO and KEGG enrichment analysis. The genes associated with these genes were identified via Cytoscape software. Immune cell infiltration and correlation analysis were used to screen the hub genes. The results revealed that the PTTG1, NCAPG, RACGAP1, PBK, ASPM, AURKA, CDCA5, KIF20A, MELK and PRC1 genes were correlated with immune targets, and these hub gene biomarkers will aid in future cancer prognosis and immunotherapy targeting in hepatocellular carcinoma patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00215-2.

13.
J Mater Chem B ; 12(11): 2906, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38421041

RESUMO

Correction for 'Investigating the effect of acidic and basic precipitation on the antibacterial activity of ZnO nanoparticles against Gram-negative and Gram-positive bacteria' by Sreekanth R. et al., J. Mater. Chem. B, 2024, 12, 2180-2196, https://doi.org/10.1039/D3TB02119J.

14.
Mol Cell Biochem ; 375(1-2): 39-47, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23212448

RESUMO

Chronic alcohol consumption causes numerous biochemical and biophysical changes in the central nervous system, in which mitochondria is the primary organelle affected. In the present study, we hypothesized that alcohol alters the mitochondrial membrane properties and leads to mitochondrial dysfunction via mitochondrial reactive oxygen species (mROS) and reactive nitrogen species (RNS). Alcohol-induced hypoxia further enhances these effects. Administration of alcohol to rats significantly increased the mitochondrial lipid peroxidation and protein oxidation with decreased SOD2 mRNA and protein expression was decreased, while nitric oxide (NO) levels and expression of iNOS and nNOS in brain cortex were increased. In addition, alcohol augmented HIF-1α mRNA and protein expression in the brain cortex. Results from this study showed that alcohol administration to rats decreased mitochondrial complex I, III, IV activities, Na(+)/K(+)-ATPase activity and cardiolipin content with increased anisotropic value. Cardiolipin regulates numerous enzyme activities, especially those related to oxidative phosphorylation and coupled respiration. In the present study, decreased cardiolipin could be ascribed to ROS/RNS-induced damage. In conclusion, alcohol-induced ROS/RNS is responsible for the altered mitochondrial membrane properties, and alcohol-induced hypoxia further enhance these alterations, which ultimately leads to mitochondrial dysfunction.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Etanol/farmacologia , Membranas Mitocondriais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Anisotropia , Córtex Cerebral/metabolismo , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Fluidez de Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Membranas Mitocondriais/enzimologia , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo I/genética , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Nitritos/metabolismo , Carbonilação Proteica , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
15.
Indian J Biochem Biophys ; 50(1): 32-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23617072

RESUMO

Alcohol-induced oxidative stress leads to imbalance between reactive oxygen species (ROS) and the antioxidant defense system, resulting in oxidative damage to membrane components such as lipids and proteins, ultimately altering membrane properties. In this study, we assessed oxidative stress status and alterations in erythrocyte membrane properties in alcohol-administered rats with respect to gender difference. Alcohol (20% v/v) administered rats of both genders showed significant changes in plasma lipid profile with elevated nitrite/nitrate levels. Furthermore, alcohol-administration significantly decreased erythrocyte antioxidant enzymes and enhanced erythrocyte membrane lipid peroxidation, cholesterol/phospholipid (C/P) ratio and Na+/K(+)-ATPase activity in both males and females. Besides, anisotropic studies revealed that alcohol-administration significantly decreased erythrocyte membrane fluidity. In conclusion, alcohol-administration significantly increased oxidative stress by decreasing antioxidant status, and subsequent generation of ROS altered membrane properties by altering fluidity and Na+/K(+)-ATPase activity. Female rats were more vulnerable to alcohol-induced biochemical and biophysical changes in plasma and erythrocyte including oxidative stress than male rats.


Assuntos
Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/fisiologia , Etanol/administração & dosagem , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Administração Oral , Animais , Feminino , Masculino , Ratos , Ratos Wistar , Fatores Sexuais
16.
3 Biotech ; 11(8): 383, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34350088

RESUMO

In this study, a cell wall-associated extracellular electron transfer (EET) was determined in the thermophilic Geobacillus sp. to utilize iron as a terminal electron acceptor. The direct extracellular transfer of its electrons was primarily linked to the cell wall cytochrome-c and diffusible redox mediators like flavins during the anoxic condition. Based on the azo dye decolouration and protein film voltammetry, it was revealed that, in the absence of surface polysaccharide and diffusible mediators, the cell wall-associated EET pathway was likely to be a favorable mechanism in Geobacillus sp. Since the permeability of such redox molecule is primarily limited to the cell wall, the electron transfer occurs by direct contact with cell wall-associated cytochrome and final electron acceptor. Furthermore, transfer of electrons with the help of redox shuttling molecules like riboflavin from cytochrome to cells, vice versa indicates that Geoabcillus sp. has adopted this unique pathway during an anoxic environment for its respiration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02917-2.

17.
Virusdisease ; 32(4): 690-702, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34307771

RESUMO

The novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) is spreading, as the causative pathogen of coronavirus disease-19 (COVID-19). It has infected more than 1.65 billion people all over the world since it was discovered and reported 3.43 million deaths by mid of May 2021. SARS-CoV-2 enters the host cell by binding to viral surface glycoprotein (S protein) with human ACE2 (angiotensin-converting enzyme2). Spike protein (contains S1 and S2 sub-domains) molecular interaction with the host cells is considered as a major step in the viral entry and disease initiation and progression and this identifies spike protein as a promising therapeutic target against antiviral drugs. Currently, there are no efficient antiviral drugs for the prevention of COVID-19 infection. In this study, we have analyzed global 8719 spike protein sequences from patients infected with SAR-CoV-2. These SAR-CoV-2 genome sequences were downloaded from the GISAID database. By using an open reading frame (ORF) tool we have identified the spike protein sequence. With these, all spike protein amino acid sequences are subjected to multiple sequence alignment (MSA) with Wuhan strain spike protein sequence as a query sequence, and it shows all SAR-CoV strain spike proteins are 99.8% identical. In the mutational analysis, we found 639 mutations in the spike protein sequence of SARS-CoV-2 and identified/highlighted 20 common mutations L5F, T22I, T29I, H49Y, L54F, V90F, S98F, S221L, S254F, V367F, A520S, T572I, D614G, H655Y, P809S, A879S, D936Y, A1020S, A1078S, and H1101Y. Further, we have analyzed the crystal structure of the 2019-nCoV chimeric receptor-binding complex with ACE2 (PDB ID: 6VW1) as a major target protein. The spike receptor binding protein (RBD) used as target region for our studies with FDA-approved drugs for repurposing, and identified few anti-SARS-CoV2 potential drugs (Silmitasertib, AC-55541, Merimepodib, XL413, AZ3451) based on their docking score and binding mode calculations expected to strongly bind to motifs of ACE2 receptor and may show impart relief in COVID-19 patients.

18.
Nitric Oxide ; 23(3): 181-6, 2010 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-20561918

RESUMO

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. Experimental subjects smoke 12+/-2 cigarettes per day for 7-10 years. In smokers elevated nitrite/nitrate levels in plasma and red cell lysates were observed. Smokers showed increased hemolysis, erythrocyte membrane lipid peroxidation, protein carbonyls, C/P ratio (cholesterol and phospholipid ratio), anisotropic (gamma) value with decreased Na(+)/K(+)-ATPase activity and sulfhydryl groups. Alterations in smokers erythrocyte membrane individual phospholipids were also evident from the study. Red cell lysate nitric oxide positively correlated with C/P ratio (r=0.565) and fluorescent anisotropic (gamma) value (r=0.386) in smokers. Smoking induced generation of reactive oxygen/nitrogen species might have altered erythrocyte membrane physico-chemical properties.


Assuntos
Membrana Eritrocítica/efeitos dos fármacos , Lipídeos de Membrana/metabolismo , Fumaça/efeitos adversos , Fumar/efeitos adversos , Adulto , Estudos de Casos e Controles , Membrana Eritrocítica/metabolismo , Hemólise/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Fluidez de Membrana/efeitos dos fármacos , Óxido Nítrico/sangue , Óxido Nítrico/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , ATPase Trocadora de Sódio-Potássio/sangue , ATPase Trocadora de Sódio-Potássio/metabolismo , Fatores de Tempo , Nicotiana
19.
Curr Comput Aided Drug Des ; 14(3): 246-252, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29493460

RESUMO

BACKGROUND: Gefitinib (lressa) is the most prescribed drug, highly effective to treat nonsmall cell lung cancer; primarily it was considered that targeted therapy is a kinase inhibitor. The nonsmall cell lung cancer is caused by mutation in the Epithelial Growth Factor Receptor (EGFR) gene. Iressa works by blocking the EGFR protein that helps the cancer cell growth. EGFR protein has lead to the development of anticancer therapeutics directed against EGFR inhibitor including Gefitinib for non-small cell lung cancer. METHODS: To explore the interaction between Gefitinib and its derivatives with crystal structure of EGFR to understand the better molecular insights interaction strategies. Molecular modeling of ligands (Gefitinib and its derivatives) was carried out by Avogadro software till atomic angle stable confirmation was obtained. The partial charges for the ligands were assigned as per standard protocol for molecular docking. All docking simulations were performed with AutoDockVina. Virtual screening was carried out based on binding energy and hydrogen bonding affinity. Molecular dynamics (MD) and Simulation EGFR were done using GROMACS 5.1.1 software to explore the interaction stability in a cell. RESULTS: The stable conformation for EGFR protein trajectories were captured at various time intervals 0-20ns. Few compounds screen based on high affinity as the inhibitor for EGFR may inhibit the cell cycle signaling in non-small cell lung cancer. CONCLUSION: These result suggested a computer-aided screening approach of Gefitinib derivatives with regard to their binding to EGFR for identifying novel drugs for the treatment of non-small cell lung cancer.


Assuntos
Receptores ErbB/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/química , Quinazolinas/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Desenho Assistido por Computador , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/química , Gefitinibe , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Software
20.
Neurotoxicol Teratol ; 63: 60-65, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28778836

RESUMO

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. Sixty day old male albino rats were treated with 20% alcohol at 5g/kg body weight/ day for sixty days. Alcohol administration significantly increased the levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyls with decreased catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD) activities and reduced glutathione (GSH) content in synaptosomes. Further, alcohol administration decreased (cholesterol/phospholipids) C/P ratio in synaptosomal membranes, which was further confirmed using 1,6 diphenyl 1,3 hexatriene (DPH) as fluorescent probe. Moreover, alcohol treatment also increased membrane bound Na+/K+-ATPase, Ca2+-ATPase and Mg2+-ATPase enzyme activities. Correlation (r) analysis revealed that anisotropic (γ) values were strongly associated with lipid peroxidation (r=0.678) and Na+/K+-ATPase activity (r=0.793). The results of the present study clearly indicate that lipid peroxidation was positively correlated (r=0.621) with Na+/K+-ATPase activity and C/P ratio was negatively associated (r=-0.549) in alcohol treated animals. Similar results were found on alcohol treatment (50 and 100mM) of brain synaptosomes in vitro. But with the co-treatment of vitamin E reversed these changes. In conclusion, synaptosomal membranes properties are impaired due to increased oxidative stress, changes in lipid composition, altered fluidity and membrane bound enzyme activities. And treatment with vitamin E renders protection against ethanol-induced membrane alterations.


Assuntos
Antioxidantes/farmacologia , Membrana Celular/efeitos dos fármacos , Etanol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sinaptossomos/efeitos dos fármacos , Vitamina E/metabolismo , Animais , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
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