Genomic Mutations in SARS-CoV-2 Genome following Infection in Syrian Golden Hamster and Associated Lung Pathologies.

The continuous evolution of the SARS-CoV-2 virus led to constant developments and efforts in understanding the significance and impacts of SARS-CoV-2 variants on human health. Our study aimed to determine the accumulation of genetic mutations and associated lung pathologies in male and female hamsters infected with the ancestral Wuhan strain of SARS-CoV-2. The present study showed no significant difference in the viral load between male and female hamsters and peak infection was found to be on day four post infection in both sexes of the animals. Live virus particles were detected up to 5 days post infection (dpi) through the TCID-50 assay, while qRT-PCR could detect viral RNA up to 14 dpi from all the infected animals. Further, the determination of the neutralizing antibody titer showed the onset of the humoral immune response as early as 4 dpi in both sexes against SARS-CoV-2, and a significant cross-protection against the delta variant of SARS-CoV-2 was observed. Histopathology showed edema, inflammation, inflammatory cell infiltration, necrosis, and degeneration of alveolar and bronchial epithelium cells from 3 dpi to 14 dpi in both sexes. Furthermore, next-generation sequencing (NGS) showed up to 10 single-nucleotide polymorphisms (SNPs) in the SARS-CoV-2 (ancestral Wuhan strain) genome isolated from both male and female hamsters. The mutation observed at the 23014 position (Glu484Asp) in the SARS-CoV-2 genome isolated from both sexes of the hamsters plays a significant role in the antiviral efficacy of small molecules, vaccines, and the Mabs-targeting S protein. The present study shows that either of the genders can be used in the pre-clinical efficacy of antiviral agents against SARS-CoV-2 in hamsters. However, considering the major mutation in the S protein, the understanding of the genetic mutation in SARS-CoV-2 after passing through hamsters is crucial in deciding the efficacy of the antiviral agents targeting the S protein. Importance: Our study findings indicate the accumulation of genomic mutations in SARS-CoV-2 after passing through the Syrian golden hamsters. Understanding the genomic mutations showed that either of the hamster genders can be used in the pre-clinical efficacy of antiviral agents and vaccines.

Bovine babesiosis: An insight into the global perspective on the disease distribution by systematic review and meta-analysis.

Bovine babesiosis is continuing as a great threat to the livestock sector causing havoc production losses with significant morbidity and mortality. Being a tick-borne disease, the great complexity in the agent-host- vector relationship has severely hampered the sincere efforts towards the development of an effective vaccine against bovine babesiosis. In these circumstances, assessing the global scenario of disease prevalence is a prerequisite to strategize the available control measures. Keeping this in view, the objective of this study was to estimate the pooled prevalence of bovine babesiosis globally. The literature search was conducted to identify all relevant published articles reporting the prevalence of bovine babesiosis and a total of 163 studies were found eligible for final systematic review and meta-analysis. Meta-analysis was conducted using meta package of R software and summary estimates of the prevalence were calculated. Meta analysis of 81099 samples from 62 countires representing six continents revealed pooled global prevalence of bovine babesiosis as 29% (95% CI = 24%-34%) with estimated prevalence of active infection as 16% (95% CI = 13%-20%) and seroprevalence as 50% (95% CI = 45%-56%) using random effects model. Continent wise highest prevalence of bovine babesiosis in South America 64% (95% CI = 49%-77%) and lowest in Asia 19% (95% CI = 14%-25%). Highest prevalence was estimated with B. bigemina 22% (95% CI = 18%-27%) and least prevalence was recorded with B. divergens 12% (95% CI = 2%-46%). The pooled prevalence estimates generated in the study is revealing an increase in disease trend and the need for immediate planning of mitigation strategies paralleled with the development of early diagnostic methods to reduce the impact of disease throughout the world.

Anticancer Properties of Different Solvent Extracts of Cucumis melo L. Seeds and Whole Fruit and Their Metabolite Profiling Using HPLC and GC-MS.

Honeydew melon (Cucumis melo L.) is an oval-shaped delicious fruit of one cultivar group of the muskmelon with immense nutritional importance and is extensively consumed by many tropical countries. The effect of various organic solvents on the recovery of phytochemicals from honeydew melon plant fruits and seeds was assessed. Further, High-Performance Liquid Chromatography (HPLC) was used to examine and assess the contents of phenolic acid (gallic acid) and flavonoid (rutin) compounds. The use of gas chromatography-mass spectrometry (GC-MS) analysis explained the presence of volatile phytocompounds in the extracts. The use of organic solvents had a substantial impact on the total dry weight and extract yield. In general, the solvent-extracted constituents remained in the order of methanol>chloroform>distilled water for both honeydew melon seeds and whole fruit. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) was used to assess the cytotoxicity effect against PC3, HCT116, HeLa, and Jurkat cell lines. The chloroform extract exhibited a good cytotoxic activity against all cell lines as compared to other solvent extracts. HPLC analysis revealed the occurrence of gallic acid content of 0.102 ± 0.23 mg/10 mg of dry whole fruit extract, while 10 mg of dry seed extract contained only 0.022 ± 0.12 mg of gallic acid content. Likewise, rutin content was observed to be 0.224 ± 0.31 mg and 0.1916 ± 0.82 mg/10 mg of dry whole fruit and seed extract, respectively. Further, GC-MS analysis revealed the presence of a total of 37 compounds in chloroform extract of whole fruit, while only 14 compounds were found in seed extract. Nevertheless, more examinations are needed to identify and characterize other metabolites from honeydew melon and evaluate their pharmacological importance.

Anticancer and Antibacterial Activities of Silver Nanoparticles (AgNPs) Synthesized from Cucumis melo L.

The current investigation reports the structural and biological evaluation of silver nanoparticles (AgNPs) biosynthesized from the pericarp extract of Cucumis melo L. (muskmelon). The AgNPs were characterized by ultraviolet-visible (UV-Vis) spectrophotometry, XRD (X-ray diffraction), SEM (scanning electron microscopy) and EDAX (energy-dispersive X-ray spectroscopy). The XRD analysis showed that biosynthesized AgNPs were having FCC (face centered cubic) crystalline structures. Further, the SEM and EDAX showed spherically shaped AgNPs having an average size of 25 nm. The AgNPs effectively inhibited the growth of Bacillus subtilis and Escherichia coli. Moreover, the cytotoxic assay of AgNPs revealed effective cytotoxicity against different cancer cells, such as HeLa, HCT-116, PC-3 and Jurkat in a dose reliant way. The cell viability was noticed to range from 50% to 60% with IC50 values ranging from 150 µg/mL to 224 µg/mL. The lower cell viability indicates the toxic effects of biosynthesized AgNPs against these malignant cells. Thus, the current study shows that these biosynthesized AgNPs could be utilized in various medical applications in near future.

The Antineuroinflammatory Effect of Simvastatin on Lipopolysaccharide Activated Microglial Cells.

Microglial cells, upon hyperactivation, produce proinflammatory cytokines and other oxidative stress mediators causing neuroinflammation, which is associated with the progress of many neurodegenerative diseases. Suppressing the microglial activation has hence been used as an approach for treating such diseases. In this study, the antineuroinflammatory effect of simvastatin was examined in lipopolysaccharide (LPS)-activated rat C6 glioma cells. The cell proliferation and cytotoxic effect of LPS and simvastatin on C6 glioma cells was evaluated by (MTT) assay. Neuroinflammation was induced in differentiated cell lines by treatment with 3.125 µg/mL of LPS for 12 h. Upon induction, the cell lines were treated with different concentrations (3.125, 6.25, 12.5, 25, 50, 100 µM) of simvastatin and incubated in a humidified CO2 incubator for 24 to 48 h. The optimum concentrations of LPS and simvastatin were found to be 3.125 µg/mL and 25 µM, respectively, with a cell viability of more than 90% at 24 h postincubation. Furthermore, proinflammatory marker expression was analyzed by flow cytometry and showed a decrease in interferon-γ, interleukin 6, nuclear factor-κB p65, and tumor necrosis factor-α in simvastatin-treated and LPS-induced neuroinflammatory cells, and the mean fluorescent values were found to be 21.75 ± 0.76, 20.9 ± 1.90, 19.72 ± 1.29, and 16.82 ± 0.97, respectively, as compared to the untreated cells. Thus, we show that simvastatin has the potential to regulate the anti-inflammatory response in microglial cells upon LPS challenge. Hence, simvastatin can be employed as a potent anti-inflammatory drug against neuroinflammatory diseases and neurodegenerative disorders.

Potential applications of engineered nanoparticles in medicine and biology: an update.

Nanotechnology advancements have led to the development of its allied fields, such as nanoparticle synthesis and their applications in the field of biomedicine. Nanotechnology driven innovations have given a hope to the patients as well as physicians in solving the complex medical problems. Nanoparticles with a size ranging from 0.2 to 100 nm are associated with an increased surface to volume ratio. Moreover, the physico-chemical and biological properties of nanoparticles can be modified depending on the applications. Different nanoparticles have been documented with a wide range of applications in various fields of medicine and biology including cancer therapy, drug delivery, tissue engineering, regenerative medicine, biomolecules detection, and also as antimicrobial agents. However, the development of stable and effective nanoparticles requires a profound knowledge on both physico-chemical features of nanomaterials and their intended applications. Further, the health risks associated with the use of engineered nanoparticles needs a serious attention.

Nanoparticles: Alternatives Against Drug-Resistant Pathogenic Microbes.

Antimicrobial substances may be synthetic, semisynthetic, or of natural origin (i.e., from plants and animals). Antimicrobials are considered "miracle drugs" and can determine if an infected patient/animal recovers or dies. However, the misuse of antimicrobials has led to the development of multi-drug-resistant bacteria, which is one of the greatest challenges for healthcare practitioners and is a significant global threat. The major concern with the development of antimicrobial resistance is the spread of resistant organisms. The replacement of conventional antimicrobials by new technology to counteract antimicrobial resistance is ongoing. Nanotechnology-driven innovations provide hope for patients and practitioners in overcoming the problem of drug resistance. Nanomaterials have tremendous potential in both the medical and veterinary fields. Several nanostructures comprising metallic particles have been developed to counteract microbial pathogens. The effectiveness of nanoparticles (NPs) depends on the interaction between the microorganism and the NPs. The development of effective nanomaterials requires in-depth knowledge of the physicochemical properties of NPs and the biological aspects of microorganisms. However, the risks associated with using NPs in healthcare need to be addressed. The present review highlights the antimicrobial effects of various nanomaterials and their potential advantages, drawbacks, or side effects. In addition, this comprehensive information may be useful in the discovery of broad-spectrum antimicrobial drugs for use against multi-drug-resistant microbial pathogens in the near future.