Continent-wide evolutionary trends of emerging SARS-CoV-2 variants: dynamic profiles from Alpha to Omicron

The ongoing SARS-CoV-2 evolution process has generated several variants due to its continuous mutations, making pandemics more critical. The present study illustrates SARS-CoV-2 evolution and its emerging mutations in five directions. First, the significant mutations in the genome and S-glycoprotein were analyzed in different variants. Three linear models were developed with the regression line to depict the mutational load for S-glycoprotein, total genome excluding S-glycoprotein, and whole genome. Second, the continent-wide evolution of SARS-CoV-2 and its variants with their clades and divergence were evaluated. It showed the region-wise evolution of the SARS-CoV-2 variants and their clustering event. The major clades for each variant were identified. One example is clade 21K, a major clade of the Omicron variant. Third, lineage dynamics and comparison between SARS-CoV-2 lineages across different countries are also illustrated, demonstrating dominant variants in various countries over time. Fourth, gene-wise mutation patterns and genetic variability of SARS-CoV-2 variants across various countries are illustrated. High mutation patterns were found in the ORF10, ORF6, S, and low mutation pattern E genes. Finally, emerging AA point mutations (T478K, L452R, N501Y, S477N, E484A, Q498R, and Y505H), their frequencies, and country-wise occurrence were identified, and the highest event of two mutations (T478K and L452R) was observed.

     

Gastric adenocarcinoma in a patient re-infected with <Emphasis Type="Italic">H. pylori</Emphasis> after regression of MALT lymphoma with successful anti-<Emphasis Type="Italic">H. pylori</Emphasis>therapy and gastric resection: a case report

Background

Helicobacter pylori (H. pylori) has been etiologically linked with primary gastric lymphoma (PGL) and gastric carcinoma (GC). There are a few reports of occurrence of both diseases in the same patient with H. pylori infection.

Case presentation

We report a patient with PGL in whom the tumor regressed after surgical resection combined with eradication of H. pylori infection. However, he developed GC on follow up; this was temporally associated with recrudescence / re-infection of H. pylori. This is perhaps first report of such occurrence.

Conclusions

Possible cause and effect relationship between H. pylori infection and both PGL and GC is discussed. This case also documents a unique problem in management of PGL in tropical countries where re-infection with H. pylori is supposed to be high.

     

Development of epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): Immunoinformatics approach

Recently, a novel coronavirus (SARS-COV-2) emerged which is responsible for the recent outbreak in Wuhan, China. Genetically, it is closely related to SARS-CoV and MERS-CoV. The situation is getting worse and worse, therefore, there is an urgent need for designing a suitable peptide vaccine component against the SARS-COV-2. Here, we characterized spike glycoprotein to obtain immunogenic epitopes. Next, we chose 13 Major Histocompatibility Complex-(MHC) I and 3 MHC-II epitopes, having antigenic properties. These epitopes are usually linked to specific linkers to build vaccine components and molecularly dock on toll-like receptor-5 to get binding affinity. Therefore, to provide a fast immunogenic profile of these epitopes, we performed immunoinformatics analysis so that the rapid development of the vaccine might bring this disastrous situation to the end earlier.     

Prion disease: a deadly disease for protein misfolding

An infectious particle, termed prion, composed largely and perhaps solely of a single protein, is the likely causative agent of prion disease. It produces lethal decline of cognitive and motor function. The responsible protein arrives at a pathogenic state by misfolding from a normal form that has ubiquitous tissue distribution. Prion diseases are often called spongiform encephalopathies. Probably most mammalian species develop these diseases. Specific examples in various animals are -Scrapie, Transmissible Mink Encephalopathy (TME ), Chronic Wasting Disease(CWD) and bovine spongiform encephalopathy (BSE). Humans are also susceptible to several prion diseases: Creutzfeld-Jacob Disease (CJD), Gerstmann-Straussler-Scheinker Syndrome (GSS), Fatal Familial Insomnia (FFI), Kuru and Alpers Syndrome. This paper reviews transmission of this diseases, protein involvement, nature of protein, the conversion process from PrP(c) to PrP(Sc), conversion of prion protein in vitro, the different proposed models for the conversion of PrP(c) to PrP(Sc), prion and other amyloid diseases, prion strains, structure of PrP(c) the particular process that may induce prion disease, and immunization against these diseases.     

Human insulin genome sequence map,biochemical structure of insulin for recombinant DNA insulin

Insulin is a essential molecule for type I diabetes that is marketed by very few companies. It is the first molecule, which was made by recombinant technology; but the commercialization process is very difficult. Knowledge about biochemical structure of insulin and human insulin genome sequence map is pivotal to large scale manufacturing of recombinant DNA Insulin. This paper reviews human insulin genome sequence map, the amino acid sequence of porcine insulin, crystal structure of porcine insulin, insulin monomer, aggregation surfaces of insulin, conformational variation in the insulin monomer, insulin X-ray structures for recombinant DNA technology in the synthesis of human insulin in Escherichia coli.     

Angiotensin II receptors and drug discovery in cardiovascular disease

Hypertension is one of the cardiovascular diseases that might cause cardiovascular remodeling and endothelial dysfunction besides high blood pressure. Angiotensin II (Ang II) receptors are implicated in hypertension. Genetic and epigenetic manipulations of the Ang II receptors play a crucial part in the programming of cardiovascular diseases, and certain variants of the Ang II type 1 and Ang II type 2 receptors are constitutively predisposed to higher cardiovascular risk and hypertension. In this review, we focus on the expression, mode of action of Ang II receptors, and their role in programming the cardiovascular diseases in utero. In addition, we discuss possible therapeutic interventions of Ang II stimulation. Collectively, this information might lead us to new drug designs against cardiovascular diseases.     

Profile of neonatal septicaemia at a district-level sick newborn care unit

Although sepsis is a major cause of morbidity and mortality among newborns in resource-poor countries, little data are available from rural areas on culture-proven sepsis. The aim of the present study was to provide information in this regard. The study reports results on the incidence and aetiology of neonatal sepsis cases admitted to a facility in a rural area in eastern India. Blood culture was done for all babies, with suspected clinical sepsis, who were admitted to the sick newborn care unit at Suri where the study was conducted during March 2009-August 2010. A standard form was used for collecting clinical and demographic data. In total, 216 neonatal blood culture samples were processed, of which 100 (46.3%) grew potential pathogens. Gram-negative infection was predominant (58/100 cases) mainly caused by enteric Gram-negative bacteria. Klebsiella pneumoniae was the most common Gram-negative isolate. The emergence of fungal infection was observed, with 40% of the infection caused by yeast. Gram-negative organisms exhibited 100% resistance to ampicillin, cefotaxime, and gentamicin. Amikacin and co-trimoxazole showed 95% (n=57) resistance, and ciprofloxacin showed 83.3% (n=50) resistance among the Gram-negative bacteria. Carbapenem showed emerging resistance (n=4; 6.6%). Results of analysis of risk factors showed an extremely significant association between gestation and sepsis and gender and sepsis. Gastrointestinal symptoms were highly specific for fungal infections. One-third of babies (n=29), who developed culture-positive sepsis, died. Blood culture is an investigation which is frequently unavailable in rural India. As a result, empirical antibiotic therapy is commonly used. The present study attempted to provide data for evidence-based antibiotic therapy given to sick newborns in such rural units. The results suggest that there is a high rate of antibiotic resistance in rural India. Urgent steps need to be taken to combat this resistance.     

Leishmania donovani infection of human myeloid dendritic cells leads to a Th1 response in CD4+ T cells from healthy donors and patients with kala-azar

The role played by dendritic cells (DCs) in Leishmania donovani infection is poorly understood. Here, we report that L. donovani amastigotes efficiently infect human peripheral-blood monocyte-derived DCs. Opsonization with normal human serum enhanced the infectivity of amastigotes and promastigotes only marginally. Surface attachment versus internalization was distinguished by incubation of DCs with live, fluorescein isothiocyanate-labeled parasites, followed by quenching with crystal violet. Infection with amastigotes was accompanied by DC maturation, as was evident from the up-regulation of maturation-associated cell-surface markers, the nuclear translocation of RelB, and the release of cytokines. Amastigote-primed DCs produced inflammatory cytokines in response to subsequent treatment with interferon- gamma or anti-CD40 monoclonal antibody. When cocultured, amastigote-infected DCs induced T helper cell type 1 (Th1) responses both in naive allogeneic CD4(+) T cells and in autologous CD4(+) T cells from patients with kala-azar and up-regulated the expression of T-bet. Our data reveal that infection with L. donovani amastigotes induces a Th1 cytokine milieu in both DCs and T cells.     

Olanzapine-induced hepatopathy in albino rats: A newer model for screening putative hepatoprotective agents, namely silymarin

Backgrounds:

This study was conducted to establish olanzapine-induced hepatopathy in Wistar albino rats as a newer model to screen putative hepatoprotective agents namely silymarin.

Materials and Methods:

Albino rats were divided into three groups, namely vehicle control group (CG), olanzapine-treated group (OZ), and olanzapine plus silymarin (OZS) treated groups. Both the OZ and OZS groups were treated with the same dose of intraperitoneal olanzapine for 6 weeks and group OZS additionally received oral silymarin. Baseline and terminal hepatic enzymes (SGOT, SGPT, and ALP) were measured in all three groups.

Results:

Histopathological examination of livers of both OZ and OZS groups showed degenerative changes, whereas those of control group showed normal architecture. Liver enzyme levels showed statistically significant rise in comparison to the control group as well as the respective base line values in both the test groups, but the differences in the rise of liver enzymes between the two test groups were not statistically significant.

Conclusion:

Olanzapine-induced hepatopathy in rats can be used as a model for screening putative hepatoprotective agents and in our setting silymarin has failed to provide any hepatoprotection.