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1.
J Biomol Struct Dyn ; : 1-15, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35014594

RESUMO

Leishmania donavani is the causative agent of leishmaniasis, responsible for social and economic disruption, especially in developing countries. Lack of effective drugs with few side effects have necessitated the discovery of newer therapeutic solutions for leishmaniasis. Glycophosphatidylinositol (GPI) synthesis plays a vital role in protozoan cell membranes structural formation and antigenic modification. Hence, any disruption in its biosynthesis can prove fatal to the parasitic protozoans. N-acetylglucosamine-phosphatidylinositol de-N-acetylase (NAGP-deacetylase) is an enzyme from the GPI biosynthetic pathway that catalyzes the deacetylation of N-acetylglucosaminylphosphatidylinositol to glucosaminylphosphatidylinositol, a step essential for the proper functioning of the enzyme. In the quest for novel scaffolds as anti-leishmaniasis agents, we have executed in silico virtual screening, density function theory, molecular dynamics and MM-GBSA based energy calculations with a natural product library and a diverse library set from Chembridge database. Two compounds, 14671 and 4610, were identified at the enzyme's active site and interacted with catalytic residues, Asp43, Asp44, His41, His147, His 150, Arg80 and Arg231. Both molecules exhibited stable conformation in their protein-ligand complexes with binding free energies for compound-14671 and compound-4610 of -54 ± 4 and -50 ± 4 kcal/mol, respectively. These scaffolds can be incorporated in future synthetic determinations, focusing on developing druggable inhibitor support, increasing potency, and introducing species selectivity.Communicated by Ramaswamy H. Sarma.

2.
New Microbes New Infect ; : 100949, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35018221

RESUMO

The COVID-19 disease caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2) has posed as a major health concern for people all across the globe. Along with the increasing confirmed patients being readmitted with complaints for fever, cough, cold, the effective monitoring of 'relapse' of the SARS-CoV-2 virus in the previously discharged patients have become the next area of focus. However, availability of limited data on reactivation of SARS-CoV-2 makes the disease prognosis as well as the effective control of re-infection an immense challenge. Prompted by these challenges, we assessed the possibility of re-infection in discharged patients and the risk of the transmission, proficiency of RT-PCR results and approximate period required for the quarantine and the real challenges for the development of vaccine. In the present review, the published literature on all the possible cases of re-infection from February to July were reported, thereby selected 142 studies from a hub of overall 669 studies after full text screening. The incomplete virus clearance, poor sensitivity of the present diagnostic testing, emergence of mutant strains, insufficient mucus collection from the throat swab etc. are some of the possible causes of re-infection. The new protocols for management of COVID-19 discharged patients should be revised in the guidelines.

3.
Redox Biol ; 49: 102228, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34979449

RESUMO

High altitude cerebral edema does not fall in routine definition of hypoxia and requires alternative therapeutic strategies. 12/15-Lipoxygenase (12/15 LOX), a key proinflammatory lipid peroxidative enzyme which site specifically inserts into cellular and subcellular membranes and plays an instrumental role in hypobaric hypoxia induced neuropathogenesis. Mitochondria, the master regulator organelles for oxygen consumption and ATP generation are sensitive to intracellular oxygen perturbations and are associated with activation of apoptosis based cell death cascades that seal the fate of the cell. The mechanistic involvement of 12/15 LOX in mitochondria mediated cell death in brain microenvironment during hypobaric hypoxia conditions can be an interesting preposition. In the present study, we have investigated underlying involvement of 12/15 LOX in hypobaric hypoxia (HH) induced disturbance in mitochondrial integrity and its relation with neuronal apoptosis. Male Balb/c mice subjected to simulated HH condition for three consecutive days showed robust increase in intra-hippocampal 12(S)HETE (12/15 LOX metabolite), which was significantly reduced following baicalein (12/15 LOX Inhibitor) treatment. The elevated level of 12(S)HETE following hypobaric hypoxia condition correlated with simultaneous increase in expression of 12/15 LOX in neurons and microglia lining the hippocampal CA3 region. Further, 12/15 LOX gets embedded onto the periphery of mitochondria following HH and a strong correlation has been observed with loss of mitochondrial integrity as evident from increased cytochrome-c in the cytosolic compartment and a subsequent upregulated activity of Caspase-3 and Caspase-9 as well as Bax/Bcl-2 expression ratio. The observed effects seen under HH were reversed upon treatment with baicalein suggesting a critical role of 12/15 LOX in HH induced mitochondrial damage Further, the hypobaric hypoxia-mediated increase in hippocampal pAKT and pmTOR protein expression were significantly ameliorated following 12/15 LOX inhibition, suggesting a mitochondrial involvement. We hereby demonstrate the contribution of 12/15 LOX in disorienting mitochondrial integrity with subsequent release of cytochrome-c in cytosol which drives the neuronal cells to intrinsic mode of cell death during hypobaric hypoxia. The protective role of baicalein by inhibition of 12/15 LOX dependent neuronal cell death and preservation of mitochondrial integrity suggests it to be a plausible therapeutic target in CNS related disorders.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34982385

RESUMO

Fast growing arsenic menace is causing serious health hazards in Bihar, India, with an estimated 10 million people at risk. The exposed population is often unaware of the problem, which only amplifies the burden of arsenic health effects. In the present study, we have assessed the current situation of arsenic exposure in Chapar village of Samastipur district, Bihar. The health of the inhabitants was assessed and correlated with (1) arsenic concentrations in the groundwater of individual wells and (2) arsenic concentration found in their hair and urine. Altogether, 113 inhabitants were assessed, and 113 hair, urine and groundwater samples were collected. The health study reveals that the exposure to arsenic has caused serious health hazard amongst the exposed population with pronounced skin manifestations, loss of appetite, anaemia, constipation, diarrhoea, general body weakness, raised blood pressure, breathlessness, diabetes, mental disabilities, diabetes, lumps in the body and few cancer incidences. It was found that 52% of the total collected groundwater samples had arsenic levels higher than the WHO limit of 10 µg/l (with a maximum arsenic concentration of 1212 µg/l) and the reduced arsenite was the predominant form in samples tested for speciation (N = 19). In the case of hair samples, 29% of the samples had arsenic concentrations higher than the permissible limit of 0.2 mg/kg, with a maximum arsenic concentration of 46 µg/l, while in 20% exposed population, there was significant arsenic contamination in urine samples > 50 µg/l. In Chapar village, the probability of carcinogenic-related risk in the exposed population consuming arsenic contaminated water is 100% for children, 99.1% for females and 97.3% for male subjects. The assessment report shared to the government enabled the village population to receive two arsenic filter units. These units are currently operational and catering 250 households providing arsenic-free water through piped water scheme. This study therefore identified a significant solution for this arsenic-exposed population.

5.
Nano Lett ; 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35030004

RESUMO

The Wiedemann-Franz law states that the charge conductance and the electronic contribution to the heat conductance are proportional. This sets stringent constraints on efficiency bounds for thermoelectric applications, which seek a large charge conduction in response to a small heat flow. We present experiments based on a quantum dot formed inside a semiconducting InAs nanowire transistor, in which the heat conduction can be tuned significantly below the Wiedemann-Franz prediction. Comparison with scattering theory shows that this is caused by quantum confinement and the resulting energy-selective transport properties of the quantum dot. Our results open up perspectives for tailoring independently the heat and electrical conduction properties in semiconductor nanostructures.

6.
J Pharm Biomed Anal ; 208: 114463, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34798393

RESUMO

The expansion of polymicrobial keratomycosis (PMK) requires dynamic pharmacotherapy of antimycotics along with antibacterial agents such as fluconazole (FCZ) and ofloxacin (OFX). To effective clinical cure, different microbes require different dosage regimens. A responsive, selective, and fast method for estimation of FCZ and OFX in rabbit tears using high-performance liquid chromatography together with tandem mass spectrometry (LC-MS/MS) was established and validated using ketoconazole as an internal standard (IS). An isocratic separation was achieved using a C18 column with methanol and aqueous 0.2% formic acid (80:20, v/v) as a mobile phase with a total run time and flow rate of 4 min and 400 µL/ min, respectively. The FCZ and OFX were detected utilizing positive ion electrospray ionization (ESI) in multiple reactions monitoring mode. The tear sample extraction was carried out using simple deproteination using methanol. The systematic method validation was carried out according to USFDA regulatory guidelines for selectivity, linearity (r2>0.99), intra-day and inter-day precision and accuracy, matrix effect, dilution integrity, and stability. The validated bioanalytical method was successfully pertained to determine the pharmacokinetics profile of FCZ and OFX marketed formulation in preclinical rabbit tears.


Assuntos
Fluconazol , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Ofloxacino , Coelhos , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray
7.
Orthop J Sports Med ; 9(11): 23259671211057851, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34881343

RESUMO

Background: Limited attention has been paid to the natural history, management, and treatment outcomes related to the posterior cruciate ligament (PCL)-deficient knee joint. Purpose: To perform a comprehensive bibliometric analysis to evaluate the 50 top-cited articles in PCL research. Study Design: Cross-sectional study. Methods: We performed a keyword-based search in the Thomson Reuters Web of Science to generate a list of the 50 most cited articles relevant to the PCL. The included articles were analyzed according to journal, country of origin, publication year, total number of citations, citations per year, citation trends, and type of study (clinical vs basic science). Results: The 50 top-cited articles were published between 1975 and 2012, and the number of individual article citations ranged between 98 and 410. The listed articles were published in 7 journals, with the American Journal of Sports Medicine contributing to more than half of the articles and citations. The United States contributed the most articles (84%) and citations (n = 4873). There were 32 clinical studies and 18 basic science studies. All clinical studies had level 4 clinical evidence, and topics included the natural history of PCL tears, factors predicting the need for surgical intervention, and long-term outcomes of isolated PCL injuries and combined capsuloligamentous injuries. Most (77.8%) of the top-cited basic science articles consisted of experimental or biomechanical studies on human cadaveric knees. Conclusion: The current analysis suggests that PCL research is still evolving and needs high-quality prospective evidence to establish sound recommendations.

8.
Big Data ; 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34881989

RESUMO

To predict the class level of any classification problem, predictive models are used and mostly a single predictive model is built to predict the class level of any classification problem; current research considers multiple predictive models to predict the class level. Ensemble modeling means instead of building a single predictive model, it is proposed to build a multilevel predictive model, which generalizes to predict all the class levels with an adequate percent of accuracy, that is, from 70% to 90% by applying and using a different combination of classification algorithms. In this article, a multilevel approach for selecting base classifiers for building an ensemble classification model is proposed. The rudimentary concept behind this approach is to drop lousy performing features and collinearity from the selected data set for ensemble modeling. For the evaluation of the proposed multilevel predictive model, different data sets from the University of California, Irvine, repository have been used and comparisons with the modern classifier's models have been conducted. The implementation analyses demonstrate the potency and excellence of the novel approach when compared with other modern classification models (three-layered artificial neural network, Radial Variant Function Neural Network/Fish Swarm Algorithm). The classification accuracy achieved with selected algorithms lies in the range of 70%-88.3%. Among all the selected classification algorithms, the lowest accuracy is achieved by the naive Bayes algorithm, which is close to 71.9%. However, the proposed algorithm (NB-RF-LR-SEMod), which is a combination of different classifiers, achieved a maximum accuracy of 88.3% on the Photographic and Imaging Manufacturers Association Diabetes data set, which is, by far, the best to any single classifier. Hence, this proposed work is helpful for any health care official to detect the diabetes problem at an early stage and prevent the affected person from future complications of it.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34855626

RESUMO

BACKGROUND: Antiretroviral options for neonates (< 28 days of life) should be expanded. We evaluated the pharmacokinetics, safety, and acceptability of the '4-in-1' fixed-dose paediatric granule formulation of abacavir/lamivudine/lopinavir/ritonavir (30/15/40/10 mg) in neonates. METHODS: The PETITE study is an ongoing phase I/II, open-label, single arm, two-stage trial conducted in South Africa. In Stage 1, term neonates exposed to HIV on standard antiretroviral prophylaxis (nevirapine +/- zidovudine) received single dose(s) of the 4-in-1 formulation followed by intensive pharmacokinetic sampling and safety assessments. At each PK visit, blood was drawn following an observed dose at 1, 2, 4, 8- and 12-hours post-dose. Here, we report the planned interim pharmacokinetic and safety analysis after completion of the single dose administration. RESULTS: Sixteen neonates, median (range) birth weight 3130 (2790-3590) g, completed 24 pharmacokinetic visits. The 4-in-1 imposed relatively high mg/kg doses of abacavir 8.6 (6.6-11.4) and lamivudine 4.3 (3.3-5.7), but lower lopinavir doses of 11.5 (8.8-15.2). Geometric mean (GM, 90% CI) AUC0-12 of abacavir, lamivudine and lopinavir were 29.87 (26.29-33.93), 12.61 (10.72-14.83) and 3.49 (2.13-5.72) µg.hr/mL, respectively. Lopinavir GM AUC0-12 was below the predefined target (20-100 µg.hr/mL) and ritonavir concentrations were only detectable in 4/120 (3%) samples. No adverse events were related to study drugs. No neonate had difficulty swallowing the 4-in-1. CONCLUSION: The high mg/kg abacavir and lamivudine doses and AUCs were safe, and the formulation well tolerated; however, lopinavir/ritonavir exposures were extremely low, preventing its use in neonates. Alternative paediatric solid antiretroviral formulations must be studied in neonates.

11.
J Neuroendocrinol ; : e13075, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34905237

RESUMO

Thyroid disease is known to affect brain metabolism and cognitive function, although the recovery of thyroid-induced brain functional changes after treatment remains unclear. We aimed to investigate the alteration in brain functional connectivity and its correlation with neuropsychological variables in hyperthyroid patients before and after anti-thyroid treatment using a resting-state functional magnetic resonance imaging (rsfMRI) technique. This is a follow-up rsfMRI study of previous work that showed impaired brain functional connectivity in hyperthyroid patients compared to healthy controls. We included rsfMRI and neuropsychological data from 21 hyperthyroid patients out of an original cohort of 28 patients, before and after anti-thyroid treatment for 30 weeks. Functional connectivity analysis and neuropsychological scores were compared using paired t tests in patients at baseline and at follow-up. Patients showed an improvement in some of the memory (p < .05) and executive, visuospatial and motor (p < .001) functions after treatment, and also showed increased functional connectivity in the regions of the right fronto-parietal network, left fronto-parietal network, and default mode network (DMN) (p < .05). At follow-up, the functional connectivity of the right fronto-parietal network showed a significantly positive correlation with the recognition of objects memory score. The overall findings suggest that anti-thyroid treatment with carbimazole improves the functional connectivity within some of the resting state networks in the hyperthyroid patients, whereas the remaining networks still show impairment.

12.
Front Hum Neurosci ; 15: 739917, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899214

RESUMO

Purpose: Patients with hyperthyroidism have frequent neuropsychiatric symptoms such as lack of attention, concentration, poor memory, impaired executive functions, depression, and anxiety. These neurocognitive impairments such as memory, attention, and executive functions appear to be associated with dysfunction in brain regions. This study was conducted to investigate the metabolic changes in the brain subcortical regions, i.e., posterior parietal cortex and dorsolateral prefrontal cortex (DLPFC), in patients with hyperthyroidism before and after antithyroid treatment using proton magnetic resonance spectroscopy (1H MRS). Materials and Methods: We collected neuropsychological and 1H MRS data from posterior parietal cortex and DLPFC, in both control (N = 30) and hyperthyroid (N = 30) patients. In addition, follow-up data were available for 19 patients treated with carbimazole for 30 weeks. The relative ratios of the neurometabolites were calculated using the Linear Combination Model (LCModel). Analysis of co-variance using Bonferroni correction was performed between healthy controls and hyperthyroid patients, and a paired t-test was applied in patients at baseline and follow-up. Spearman's rank-order correlation was used to analyze bivariate associations between thyroid hormone levels and metabolite ratios, and the partial correlation analysis was performed between neuropsychological scores and metabolite ratios, with age and sex as covariates, in the patients before and after treatment. Results: Our results revealed a significant decrease in choline/creatine [glycerophosphocholine (GPC) + phosphocholine (PCh)/creatine (tCr)] in both the posterior parietal cortex and DLPFC in hyperthyroid patients, and these changes were reversible after antithyroid treatment. The posterior parietal cortex also showed significantly reduced glutamate/creatine (Glu/tCr), (glutamate + glutamine)/creatine (Glx/tCr), and increased glutathione/creatine (GSH/tCr) ratios in the hyperthyroid patients over control subjects. In DLPFC, only (N-acetyl aspartate + N-acetyl aspartyl-glutamate)/creatine (NAA + NAAG)/tCr was increased in the hyperthyroid patients. After antithyroid treatment, (GPC + PCh)/tCr increased, and Glx/tCr decreased in both brain regions in the patients at follow-up. Gln/tCr in the posterior parietal cortex was decreased in patients at follow-up. Interestingly, (GPC + PCh)/tCr in DLPFC showed a significantly inverse correlation with free tri-iodothyronine (fT3) in hyperthyroid patients at baseline, whereas NAA/tCr showed positive correlations with fT3 and free thyroxine (fT4) in hyperthyroid patients before and after antithyroid treatment, in the posterior parietal cortex. In DLPFC, only (NAA + NAAG)/tCr showed positive correlations with fT3 and fT4 in the patients before treatment. Conclusion: The overall findings suggest that all the brain metabolite changes were not completely reversed in the hyperthyroid patients after antithyroid treatment, even after achieving euthyroidism.

13.
ACS Omega ; 6(49): 33370-33388, 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34926887

RESUMO

Gene therapy has the therapeutic potential to address a multitude of health problems, and it also has utility in different domains of science. However, its applications are plagued due to the absence of a suitable, safe, efficient, selective, and universal vector, which could help in delivering the desired nucleic acid cargo to the site of action. Though viral vectors are efficient, they pose various health risks. Different types of synthetic agents have been tried as nucleic acid vectors by researchers but with limited success. Gemini amphiphiles (GAs) are a class of synthetic surfactants having biscationic heads with attached hydrophilic and lipophilic groups. Herein, we synthesized two classes of GAs differing in the chemical nature and length of the linkers, head groups, and lipophilic chains. The resulting compounds were evaluated for their efficiency to transfect A549 and HeLa cell lines with a ß-galactosidase reporter plasmid. A 3-oxypentyl linker, a monohydroxyethyl head group, and a tetradecyl moiety as the lipophilic chain offered the best transfection efficiency (compound 10BIII). Dioleoylphosphatidylethanolamine (DOPE) as the helper lipid improved the transfection efficacy of the GAs in the absence of serum. In the presence of serum, DOPE and cholesterol, as the helper lipids, improved the transfection efficacy of the resulting formulations. The synthesized GAs showed concentration-dependent toxicity in the MTT assay. Biodistribution studies using 99mTc-labeled lipoplexes indicated that the lipoplexes got concentrated in some vital organs such as the spleen, liver, and lungs.

14.
Comput Math Methods Med ; 2021: 7433186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966444

RESUMO

Bone cancer is considered a serious health problem, and, in many cases, it causes patient death. The X-ray, MRI, or CT-scan image is used by doctors to identify bone cancer. The manual process is time-consuming and required expertise in that field. Therefore, it is necessary to develop an automated system to classify and identify the cancerous bone and the healthy bone. The texture of a cancer bone is different compared to a healthy bone in the affected region. But in the dataset, several images of cancer and healthy bone are having similar morphological characteristics. This makes it difficult to categorize them. To tackle this problem, we first find the best suitable edge detection algorithm after that two feature sets one with hog and another without hog are prepared. To test the efficiency of these feature sets, two machine learning models, support vector machine (SVM) and the Random forest, are utilized. The features set with hog perform considerably better on these models. Also, the SVM model trained with hog feature set provides an F1-score of 0.92 better than Random forest F1-score 0.77.

15.
Front Microbiol ; 12: 780458, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917058

RESUMO

Phyllosphere-the harsh foliar plant part exposed to vagaries of environmental and climatic variables is a unique habitat for microbial communities. In the present work, we profiled the phyllosphere microbiome of the rice plants using 16S rRNA gene amplicon sequencing (hereafter termed metabarcoding) and the conventional microbiological methods (culturomics) to decipher the microbiome assemblage, composition, and their functions such as antibiosis and defense induction against rice blast disease. The blast susceptible rice genotype (PRR78) harbored far more diverse bacterial species (294 species) than the resistant genotype (Pusa1602) that showed 193 species. Our metabarcoding of bacterial communities in phyllomicrobiome revealed the predominance of the phylum, Proteobacteria, and its members Pantoea, Enterobacter, Pseudomonas, and Erwinia on the phyllosphere of both rice genotypes. The microbiological culturomic validation of metabarcoding-taxonomic annotation further confirmed the prevalence of 31 bacterial isolates representing 11 genera and 16 species with the maximum abundance of Pantoea. The phyllomicrobiome-associated bacterial members displayed antifungal activity on rice blast fungus, Magnaporthe oryzae, by volatile and non-volatile metabolites. Upon phyllobacterization of rice cultivar PB1, the bacterial species such as Enterobacter sacchari, Microbacterium testaceum, Pantoea ananatis, Pantoea dispersa, Pantoea vagans, Pseudomonas oryzihabitans, Rhizobium sp., and Sphingomonas sp. elicited a defense response and contributed to the suppression of blast disease. qRT-PCR-based gene expression analysis indicated over expression of defense-associated genes such as OsCEBiP, OsCERK1, and phytohormone-associated genes such as OsPAD4, OsEDS1, OsPR1.1, OsNPR1, OsPDF2.2, and OsFMO in phyllobacterized rice seedlings. The phyllosphere bacterial species showing blast suppressive activity on rice were found non-plant pathogenic in tobacco infiltration assay. Our comparative microbiome interrogation of the rice phyllosphere culminated in the isolation and identification of agriculturally significant bacterial communities for blast disease management in rice farming through phyllomicrobiome engineering in the future.

16.
J Biomol Struct Dyn ; : 1-16, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766874

RESUMO

The increased multidrug resistance in Acinetobacter baumannii (A. baumannii) to the present-day known antibiotics has stimulated academic and industrial efforts globally for the development of novel antibacterial agents. Natural compounds as potential drug leads are gaining significant attention due to their less toxic and more tolerant nature. In the current study, the natural product-based compounds were explored as probable inhibitors of UDP-N-acetylmuramoyl-L-alanine:D-glutamate (MurD) ligase from A.baumannii (AbMurD) to provide a new class of drug leads. The prepared natural library of 3,16,714 compounds from ZINC database was screened into the active site of AbMurD using in silico high-throughput virtual screening which resulted in 100 compounds having high binding affinities. Further screening through flexible molecular docking yielded four potential compounds selected on the basis of estimated binding affinity (ΔG) and favorable protein-ligand interactions. MD simulation of these four compounds under physiological conditions and free binding energy calculations using MM/PBSA (molecular mechanics with Poisson- Boltzmann and surface area solvation) approach revealed three compounds ZINC08879777, ZINC30726863, and ZINC95486217 as potential binders of AbMurD. The calculated physicochemical and ADME properties of these compounds revealed that they can be exploited and modified to improve their binding affinity with the enzyme. Two compounds were purchased and tested against bacterial cell cultures of A. baumannii, Salmonella Typhi, and Staphylococcus aureus to determine their broad-spectrum antibacterial activity. The results suggest that the identified compounds can be exploited as potential herbal leads to target both Gram-positive and Gram-negative pathogens. Communicated by Ramaswamy H. Sarma.

17.
J Biomol Struct Dyn ; : 1-11, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34766876

RESUMO

Pathogenic RNA viruses are emerging as one of the major threats and posing challenges to human community. RNA viruses have an exceptionally shorter generation time and easy to adapt in host cells. The recent emergence of SARS-CoV-2, a long RNA virus, has shown us how difficult it is to overcome this kind of pandemic without understanding the viral infection and replication mechanisms. It is essential to comprehend replications of the viral genome, including RNA polymerization and the final capping process. The mRNAs of SARS-CoV-2 coronaviruses are protected at their 5'-ends by cap structure. The cap-like system plays a significant role in viral translational process, viral RNA stability, and scatting in detecting innate immune recognition in host cells. Two coronavirus enzymes, Nsp14 and Nsp16, critically help in the formation of capping and are considered as potential drug targets for antiviral therapy. Natural and herbal medicines have a past record of treating various acute respiratory diseases. In this work, we have exploited 56000 natural compounds to screen potential inhibitors against NSP16. In silico virtual screening, docking and Molecular Dynamics (MD) simulation studies were performed to understand how these potential inhibitors are bound to NSP16. We observed that the most highly screened compound binds to protein molecules with a high dock score, primarily through hydrophobic interactions and hydrogen bonding, as previously reported for NSP16. Compound-13 (2-hydroxy-N-({1-[2-hydroxy-1-(hydroxymethyl)ethyl]piperidin-3-yl}methyl)-5-methylbenzamide) and compound-51 (N-(2-isobutoxybenzyl)-N,2-dimethyl-2,8-diazaspiro[4.5]decane-3-carboxamide) occupied in active site along with good pharmokinetices properties. In conclusion, the selected compounds could be used as a novel therapeutic against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

18.
Inorg Chem ; 60(23): 17529-17536, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34807593

RESUMO

A novel ligand N,N'-bis(N″,N″-diethyl carbamoyl) piperazine (BDECP), L1, is synthesized as a selective precipitant for hexavalent actinyl (UO22+ and PuO22+) ions from an aqueous nitric acid medium. The ligand BDECP forms an infinite one-dimensional coordination polymer with uranyl nitrate and behaves as a bridging bidentate neutral donor. There is an alternate repetition of [UO2(NO3)2] and BDECP units as evidenced by single-crystal X-ray diffraction. Uranyl ion (UO22+) can be precipitated in >99% yield from an aqueous nitric acid medium. L1 shows fast kinetics of precipitation of uranyl ion as compared to those of other reported ligands like N-alkyl pyrolidone and N-(1-adamantyl) acetamide. Avrami's coefficient, obtained from the Avrami-Erofe'ev equation, shows that the precipitation mechanism is controlled by the phase boundary and not governed by diffusion. Theoretical studies of the uranyl complex of L1 show that there is no thermodynamic preference for L1 as compared to other potential amide-based precipitants. The principal factors that govern the fast kinetics of precipitation are the aqueous solubility and higher charge density on the amide oxygen of L1.

19.
Indian J Community Med ; 46(3): 405-410, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759476

RESUMO

Background: The Government of India initiated different programs to reduce neonatal mortality. However, the variability of neonatal deaths occurs among states of India. Objective: This study aimed to identify the differential determinants associated with neonatal deaths in northern and southern regions of India. Materials and Methods: Bivariate analysis and Cox regression analysis have been performed to evaluate the predictors of neonatal mortality from National Family Health Survey (NFHS-4) data. Results: For neonatal mortality, mother and child factors became more consistent in the southern region than northern regions of the country, while household factor was almost the same in both regions of India. Conclusions: Primary intervention is also required to reduce public health problem as neonatal mortality. It should be focused on education of mother, birth interval, age at birth, antenatal care, poverty reduction programs, and proper heath facility to pregnant mothers.

20.
Indian J Community Med ; 46(3): 434-437, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759482

RESUMO

Objective: The present study aimed to identify the determinants of adverse pregnancy outcomes (abortion, miscarriage, and stillbirth) among women aged 15-49 years in India. Methodology: Data for the analysis were taken from the latest survey of the National Family Health Survey 2015-2016. The determinants associated with abortion, miscarriage, and stillbirth among women in the age group of 15-49 years were identified. The analysis was done using adjusted binary logistic regression. Results: The contributory variables such as age, level of education, type of residence, wealth status, caste, religion, body mass index (BMI), and anemia level were found to be significantly associated with adverse pregnancy outcomes. The risk of adverse pregnancy outcomes was significantly associated with all the selected predictors. Conclusion: This study revealed that high prevalence of adverse pregnancy outcomes was found in India. The association between sociodemographic variables and the pregnancy outcomes are attributed to the fact that there is a lack of availability of fundamental health-care services for young women.

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