ABSTRACT
With an increasing fatality rate, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has emerged as a promising threat to human health worldwide. SARS-CoV-2 is a member of the Coronaviridae family, which is transmitted from animal to human and because of being contagious, further it transmitted human to human. Recently, the World Health Organization (WHO) has announced the infectious disease caused by SARS-CoV-2, which is known as coronavirus disease-2019 (COVID-2019) as a global pandemic. But, no specific medications are available for the treatment of COVID-19 so far. As a corollary, there is a need for a potential vaccine to impede the progression of the disease. Lately, it has been documented that the nucleocapsid (N) protein of SARS-CoV-2 is responsible for viral replication as well as interferes with host immune responses. We have comparatively analyzed the sequences of N protein of SARS-CoV-2 for the identification of core attributes and analyzed the ancestry through phylogenetic analysis. Subsequently, we have predicted the most immunogenic epitope for T-cell as well as B-cell. Importantly, our investigation mainly focused on major histocompatibility complex (MHC) class I potential peptides and NTASWFTAL interacted with most human leukocyte antigen (HLA) that are encoded by MHC class I molecules. Further, molecular docking analysis unveiled that NTASWFTAL possessed a greater affinity towards HLA and also available in a greater range of the population. Our study provides a consolidated base for vaccine design and we hope that this computational analysis will pave the way for designing novel vaccine candidates.
ABSTRACT
Objective: To verify possible associations between polymorphisms of glutathione S-transferase Mu (GSTM1), glutathione S-transferase θ (GSTT1) and glutathione S-transferase Pi (GSTP1) genes and susceptibility to lung cancer. Methods: A total of 106 lung cancer patients and 116 controls were enrolled in a case-control study. The GSTM1 and GSTT1 were analyzed using PCR while GSTP1 was analyzed using PCR-restriction fragment length polymorphism. Risk of lung cancer was estimated as odds ratio at 95% confidence interval using unconditional logistic regression models adjusting for age, sex, and tobacco use. Results: GSTM1 null and GSTT1 null genotypes did not show a significant risk for developing lung cancer. A significantly elevated lung cancer risk was associated with GSTP1 heterozygous, mutant and combined heterozygous+mutant variants of rs1695. When classified by tobacco consumption status, no association with risk of lung cancer was found in case of tobacco smokers and nonsmokers carrying null and present genotypes of GSTM1 and GSTT1. There is a three-fold (approximately) increase in the risk of lung cancer in case of both heterozygous (AG) and heterozygous+mutant homozygous (AG+GG) genotypes whereas there is an eightfold increase in risk of lung cancer in cases of GG with respect to AA genotype in smokers. Conclusions: Carrying the GSTM1 and GSTT1 null genotype is not a risk factor for lung cancer and GSTP1Ile105Val is associated with elevated risk of lung cancer.
ABSTRACT
OBJECTIVE: We investigated the effects of antipsychotics on immune-challenged peripheral blood mononuclear cell (PBMC) cultures. METHODS: Blood samples were collected from twelve patients with first-episode schizophrenia. The PBMCs were separated and cultures were prepared and stimulated with lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly[I:C]), and then separately treated with a typical antipsychotic (haloperidol) or atypical antipsychotic (clozapine, quetiapine, or risperidone). Pro-inflammatory (interferon gamma [IFN-gamma]) and anti-inflammatory (interleukin [IL]-4 and IL-10) cytokine levels were measured in the LPS- or poly(I:C)-stimulated PBMC cultures treated with antipsychotics. RESULTS: Haloperidol and quetiapine significantly increased the IL-4 levels (p<0.05) in LPS-stimulated PBMC cultures, while clozapine and quetiapine significantly enhanced the IL-4 levels (p<0.05) in poly(I:C)-stimulated PBMC cultures. Only treatment with haloperidol resulted in a significant increase in IL-10 production (p<0.05) in LPS-stimulated PBMC cultures, whereas clozapine, quetiapine, and risperidone treatment significantly increased IL-10 production (p<0.05) in poly(I:C)-stimulated PBMC cultures. All of the antipsychotics reduced the IFN-gamma level significantly (p<0.05) in LPS- and poly(I:C)-stimulated PBMC cultures. CONCLUSION: Antipsychotic treatment altered immune function by raising the levels of anti-inflammatory cytokines (IL-4 and IL-10) and suppressing the levels of pro-inflammatory cytokines (IFN-gamma).
