Variants of SARS-CoV-2, their effects on infection, transmission and neutralization by vaccine-induced antibodies.

OBJECTIVE: The current study reviewed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) variants for their effects on infection, transmission and neutralization by vaccine-induced antibodies. MATERIALS AND METHODS: The research articles for the current study were searched over PubMed, Google Scholar, EMBASE and Web of Science online databases. The keywords used were: (("SARS-CoV-2" OR "COVID-19") AND ("mutation" OR "variant") AND ("death" OR "hospitalization" OR "infection" OR "transmission") AND ("antibody" OR "neutralize" OR "vaccine")). A total of 333 research articles were retrieved through online-database search. These articles were further scrutinized for their relevancy. Additionally, searches were performed to find the latest relevant information over Google search engine and relevant news browsers. Finally, around 35 germane articles were considered for scripting the current report. RESULTS: The mutations have changed amino acids at key positions in spike protein viz. S477N, E484K, Q677H, E484Q, L452R, K417T, K417N and N501Y. These mutations are relevant for different characteristics and are present in newly evolved strains of SARS-CoV-2 like E484K in B.1.526, B.1.525, P.2, B.1.1.7, P.1 and B.1.351. Mutations have increased the immune escape potential leading to 3.5-6.5-folds decrease in neutralization of antibodies (Pfizer and Moderna vaccines). The variant, B.1.617 circulating in India and many other countries (double variant) having E484Q and L452R mutations, has raised the infection rate and decreased the neutralization capacity of the vaccine-induced antibodies. Deadly K417N+E484K+N501Y triplet mutations found in B.1.351 and P.1 have increased the transmission ability of these strains by 50% leading to greater COVID-19 hospitalization, ICU admissions and deaths. CONCLUSIONS: The new SARS-CoV-2 variants have compromised the neutralization potential of the currently used vaccines, but still, they have considerable efficacy to reduce infection and mortality. GRAPHICAL ABSTRACT: https://www.europeanreview.org/wp/wp-content/uploads/Graphical_Abstract.jpg.

Phytochemicals induce apoptosis by modulation of nitric oxide signaling pathway in cervical cancer cells.

OBJECTIVE: Nitric Oxide (NO) is produced by NO synthases (NOS) and is a key signaling molecule that regulates tumorigenesis, both aiding and alleviating it. Elevated NO levels are cytotoxic to cancer cells, making NOS an important target for cancer treatment. In the present study, the modulatory effects of the phytochemicals, quercetin, sulforaphane, genistein, and epigallocatechin-3-gallate on NO pathway and apoptosis were shown in HeLa cervical cancer cells. MATERIALS AND METHODS: Fluorescent microscopy and flow cytometry were used to assess apoptosis. A Griess assay was used to quantitatively measure NO, quantitative PCR array was used to assess the expression levels of genes involved in the NO signaling pathway, and immunocytochemistry was used to determine NOS protein expression. The functional association among the modulated genes was evaluated using network biology analysis, gene set enrichment, and KEGG pathway analysis. RESULTS: Treatment with the phytochemicals elevated NO levels in HeLa cells and modulated various genes involved in nitric oxide biosynthesis, superoxide metabolism, and oxidative stress, including NOS1, NOS2, NOS3, ALOX12, and SOD2, with a concomitant increase in NOS2 and NOS3 protein expression levels; also, the phytochemicals were found to induce apoptosis. CONCLUSIONS: These results suggest that the phytochemical-induced cell death is partially attributed to the activation of the NO pathway and upregulation of pro-oxidant ROS generators. Further experimental studies are required to explore this mechanistic association of NO signaling pathway activation and induction of apoptosis in other types of cancer.

The ß-ketoacyl-ACP synthase from Mycobacterium tuberculosis as potential drug targets.

The continuous preventive measures and control of tuberculosis are often hampered by re-emergence of multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis. A novel drug approach is desperately needed to combat the global threat posed by MDR strains. In spite of current advancement in biological techniques viz. microarray and proteomics data for tuberculosis, no such potent drug has been developed in the past decades yet. Therefore, mycolic acid is an essential constituent which is involved in the formation of cell wall of Mycobacterium species. The biosynthesis of mycolic acid is involved in two fatty acid synthase systems, the multifunctional polypeptide fatty acid synthase I (FASI) which performs de novo fatty acid synthesis and dissociate FASII system. FASII system consists of monofunctional enzymes and acyl carrier protein (ACP), elongating FASI products to long chain mycolic acid precursor. In this review, the ß-ketoacyl-ACP synthases (fadH, kasA and kasB) are distinct and play a vital role in mycolic acid synthesis, cell wall synthesis, biofilm formation and also pathogenesis. On the basis of substantial observation we suggest that these enzymes may be used as promising and attractive targets for novel anti-TB drugs designing and discovery.

Fluorosis in Maharashtra.

In all 241 school going children from the adjacent villages in Rajura taluka of Chandrapur district in Maharashtra were screened for dental fluorosis. Additionally 38 adult persons were also screened. The population in these villages appears to be at risk for fluorosis. Water fluoride level of 20 ppm from the village Dhoptala is the highest reported fluoride concentration in drinking water sources in the state. The entire area needs further investigations.

Renal involvement in chronic pulmonary tuberculosis.

Fifty indoor patients of chronic pulmonary tuberculosis were studied for renal involvement. There were 36 (72%) males and 14 (28%) females. Age of the patients was ranging from 16 to 70 years. Most of the patients were receiving treatment for tuberculosis for more than 1 year. Frequency of micturition and dysuria were the commonest symptoms observed. Urine smear for mycobacteria was negative in all patients however culture was positive in 6% patients. Renal biopsy was attempted in all patients but was successful in 35 patients. It revealed interstitial nephritis in 28.5%; amyloidosis in 17.1%, glomerulonephritis in 17.1%, tubercular pyelonephritis in 5.6%; pyelonephritis combined with amyloidosis in 8.5% patients. Non-specific changes were observed in 14.3% patients and in 8.5% patients tissue was inadequate for biopsy study.