Search

Kyasanur forest disease is a neglected zoonotic disease caused by a single-stranded RNA-based flavivirus, the incidence of which was first recorded in 1957 in the Southern part of India. Kyasanur forest disease virus is transmitted to monkeys and humans through the infected tick bite of Haemophysalis spinigera. Kyasanur forest disease is a febrile illness, which in severe cases, results in neurological complications leading to mortality. The current treatment regimens are symptomatic and supportive, and no targeted therapies are available for this disease. In this study, we evaluated the ability of FDA-approved drugs sofosbuvir (and its active metabolite) and Dasabuvir to inhibit the RNA-dependent RNA polymerase activity of NS5 protein from the Kyasanur forest disease virus. NS5 protein containing the N-terminal methyl transferase domain and C-terminal RNA-dependent RNA polymerase domain was expressed in Escherichia coli , and RNA-dependent RNA polymerase activity was demonstrated with the purified protein. The RNA-dependent RNA polymerase assay conditions were optimized, followed by the determination of apparent K m,ATP to validate the enzyme preparation. Half maximal-inhibitory concentrations against RNA-dependent RNA polymerase activity were determined for Sofosbuvir and its active metabolite. Dasabuvir did not show detectable inhibition with the tested conditions. This is the first demonstration of the inhibition of RNA-dependent RNA polymerase activity of NS5 protein from the Kyasanur forest disease virus with small molecule inhibitors. These initial findings can potentially facilitate the discovery and development of targeted therapies for treating Kyasanur forest disease. • Non-structural protein 5 (NS5) of the Kyasanur forest disease virus (KFDV) was recombinantly expressed and purified. • The FDA-approved drug Sofosbuvir and its metabolite inhibited the RNA-dependent RNA polymerase activity of KFDV NS5. • Sofosbuvir and its metabolite can be used as starting points for the discovery of drugs against Kyasanur forest disease. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles (ZnO NPs) are one of the most abundant metal oxides nanoparticles. It provides excellent thermal, electrical and chemical stabilities with low biotoxicity; its photo-oxidising and photo-catalytic impact on biological and chemical species is of great importance, thereby making it a promising candidate to be used for in vitro and in vivo studies in biomedical field. Hereby, ZnO NPs were synthesized using precipitation method with zinc acetate and sodium hydroxide as starting materials. This study has characterized the synthesized ZnO NPs using different techniques such as UV-Visible spectroscopy indicating a peak at 365 nm wavelength, size of ZnO NPs was determined to be 286.7 nm by measuring hydrodynamic radii using Dynamic Light Scattering (DLS) phenomena. Further predominant charge existing at surface of the synthesised ZnO NPs was evaluated to be 31.6 mV. Anti-microbial activity of ZnO NPs was determined by Kirby-Bauer method for both Gram-positive and Gram-negative bacteria, S. aureus and E. coli, respectively. Anti-microbial activity was determined as Zone of Inhibition that measures both bactericidal and bacteriostatic activity of ZnO NPs and was found to be more potent for Gram-positive (S. aureus) bacteria and its activity increased with increasing concentration of nanoparticles. Growth kinetics was studied to determine percentage growth inhibition, for this optical density was recorded as a function of time in bacterial culture broth with and without treatment. Further DNA fragmentation assay was performed to determine genotoxicity caused by nanoparticles and its effect on genomic DNA of bacteria. Highlighting its potential role as a nano-carrier system for leading antibacterial drugs for enhanced effectiveness of the antibacterial therapies. [ABSTRACT FROM AUTHOR]

Background: Dengue is a global arboviral threat to humans; causing 390 million infections per year. The availability of safe and effective tetravalent dengue vaccine is a global requirement to prevent epidemics, morbidity, and mortality associated with it. Methods: Five experimental groups (6 mice per group) each of 5-week-old BALB/c mice were immunized with vaccine and placebo (empty plasmid) (100 µg, i.m.) on days 0, 14 and 28. Among these, four groups (one group per serotype) of each were subsequently challenged 3 weeks after the last boost with dengue virus (DENV) serotypes 1-4 (100 LD50, 20 µl intracerebrally) to determine vaccine efficacy. The fifth group of each was used as a control. The PBS immunized group was used as mock control. Serum samples were collected before and after subsequent immunizations. EDIII fusion protein expression was determined by Western blot. Total protein concentration was measured by Bradford assay. Neutralizing antibodies were assessed by TCID50-CPE inhibition assay. Statistical analysis was performed using Stata/IC 10.1 software for Windows. One-way repeated measures ANOVA and Mann-Whitney test were used for neutralizing antibody analysis and vaccine efficacy, respectively. Results: The recombinant EDIII fusion protein was expressed adequately in transfected 293T cells. Total protein concentration was almost 3 times more than the control. Vaccine candidate induced neutralizing antibodies against all four DENV serotypes with a notable increase after subsequent boosters. Vaccine efficacy was 83.3% (DENV-1, -3, -4) and 50% (DENV-2). Conclusion: Our results suggest that vaccine is immunogenic and protective; however, further studies are required to improve the immunogenicity particularly against DENV-2. [ABSTRACT FROM AUTHOR]

Solution combustion procedure was used to create a succession of Na3LaxSm1 − x(PO4)2 (x = 0.01–0.15 mol) nanocrystals that generate a warm deep reddish light. Both HR-TEM and X-ray diffraction examinations were used to examine the morphology and crystalline phase analysis. Energy-dispersive X-ray analysis (EDAX) approves the elemental examination. The luminescence spectrum exhibits a decent reddish-orange emission at 700 nm wavelength upon near-UV illumination, which aligns with the electronic transition 4G5/2 → 6H11/2. According to Dexter’s idea, nearest neighbor interlinkages are responsible for the concentration quenching that occurs after the Sm3+ ion composition reaches 6 mol%. Additionally, a detailed evaluation of the radiative lifespan (0.7519 ms), quantum efficiency (77%), Non radiative rate (307.40), color temperature (3170 K), color purity (99.2%) and color coordinates (0.652, 0.338) was conducted. The optical characteristics that have been observed indicate that Sm3+ doped Na3La(PO4)2 phosphors could be a good option for improving WLED efficiency and color quality. [ABSTRACT FROM AUTHOR]

We ascertained the burden, determinants, and care cascade in the young and middle-aged patients having co-existing hypertension (HTN), Diabetes Mellitus (DM), and abdominal obesity in India from a secondary data analysis of nationally representative data. The study examined cross-sectional data from the National Family Health Survey (NFHS-5) conducted in India from 2019 to 2021 in 788974 individuals aged 15-49 years including 695707 women and 93267 men. The weighted prevalence of DM-HTN comorbidity with high waist circumference in the sample was 0.75% (95% CI: 0.71 to 0.79) including 46.33% (95% CI: 44.06 to 48.62) newly diagnosed cases detected for HTN and high blood sugars. The weighted prevalence of Metabolic syndrome as per NCEP ATPIII criteria was found to be 1.13% (95% CI: 1.08 to 1.17). Only 46.16% existing cases were treated with both anti-diabetes and antihypertensive medication (full treatment), while 34.71% cases were untreated. On adjusted analysis, increasing age, females, higher wealth index, high fat diet, obesity and comorbidities were significantly associated with having DM-HTN comorbidity along with high-waist circumference. More than half of young and middle aged-population in India with DM-HTN-abdominal obesity triad are not initiated on treatment for DM and HTN comorbidities, while a majority of the previously diagnosed cases have uncontrolled blood pressure and poor glycemic control. The poor cascade of care for DM and HTN in these high-risk group of patients may substantially increase their risk for early progression and severity of microvascular and macrovascular complications especially cardiovascular disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Basu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)