Akhilesh Kumar

RNA viruses, such as influenza, MERS, SARS-CoV, and SARS-CoV-2, have been the cause of several epidemics and pandemics in recent years and, therefore, pose a significant threat to global human heal...

MicroRNAs (miRNAs) are small, non-coding molecules that act as essential post-transcriptional regulators in various biological processes. Many studies suggest that miRNAs may modulate the host’s immune response during virus infections. We analyzed publicly available transcriptomics data involving infection with different RNA viruses and identified the most prominent candidate, miR-203a-3p. This miRNA is upregulated during H7N9, HCV, and DENV2 infections. Interestingly, pathway analysis of microRNA-targeted genes shows that miR-203a-3p targets multiple genes of the type-I interferon and JAK-STAT pathway. In this study, we reported the novel role of miR-203a-3p as it is elevated in response to polyinosinic-polycytidylic acid [poly(I:C)] transfection and infection with various RNA viruses such as Newcastle Disease Virus (NDV) and A/PR8/H1N1 influenza virus. We found that miR-203a-3p promotes the A/PR8/H1N1 virus replication by suppressing the host’s type-I interferons and interferon-stimulated genes. We demonstrated that the miR-203a-3p overexpression reduced the expression of ISGs and is attributed to the direct binding of miR-203a-3p to 3’ UTRs of Janus-activated kinase 1 (JAK1), STAT1, SOCS3, and multiple IFNA transcripts. Altogether, these findings strongly suggest that miR-203a-3p plays a pivotal role in immune homeostasis by regulation of type I IFN and supports A/PR8/H1N1 and NDV infection by targeting multiple genes of the host’s type I IFNs and JAK-STAT signaling pathways.

Anxiety is a widespread psychological disorder affecting both humans and animals. It is a typical stress reaction; however, its longer persistence can cause severe health disorders affecting the day-to-day life activities of individuals. An intriguing facet of the anxiety-related disorder can be addressed better by investigating the role of neurotransmitters in regulating emotions, provoking anxiety, analyzing the cross-talks between neurotransmitters, and, most importantly, identifying the biomarkers of the anxiety. Recent years have witnessed the potential role of the gut microbiota in human health and disorders, including anxiety. Animal models are commonly used to study anxiety disorder as they offer a simpler and more controlled environment than humans. Ultimately, developing new strategies for diagnosing and treating anxiety is of paramount interest to medical scientists. Altogether, this review article shall highlight the intricate mechanisms of anxiety while emphasizing the emerging role of gut microbiota in regulating metabolic pathways through various interaction networks in the host. In addition, the review will foster information about the therapeutic interventions of the anxiety and related disorder. Graphical abstract

The regulation of cell death in eukaryotic cells is a fundamental process for the adaptation to stress or for the response to signals. Recent studies showed that an evolutionarily conserved enzyme, arginyltransferase1 (ATE1), which is known to induce protein degradation via the N‐end rule pathway, is also involved in cell death. Particularly, ATE1 is elevated under acute oxidative stress conditions and is causing apoptosis in yeast and mammalian cells. However, how does ATE1 mediate cell death remains unknown. Here, by using budding yeast as a test model, we found that ATE1 is colocalized with mitochondria under oxidative stress, and that this translocation is essential for ATE1‐induced apoptosis. We also found that the mutations which disrupt the arginylation activity also compromise the ATE1‐induced cell death, without affecting its mitochondrial localization. Furthermore, we found that the ATE1‐mediated cell death is not dependent on mitochondrial ETC activity or the caspase pathway. Rather, we found that ATE1‐mediated cell death is dependent on the mitochondrial permeability pore and the apoptosis‐inducing factor. We conclude that ATE1 is a novel apoptosis‐regulator that utilizes specific mitochondrial pathways.

Background: Chemotherapy induced nausea and vomiting (CINV) remains one of the most common and debilitating complications of highly emetogenic chemotherapy (HEC). This study was undertaken to evaluate palanosetron against other 5-HT3 receptor antagonists in preventing delayed CINV with the aim of achieving complete response (CR) and improving quality of life (QoL).Methods: This was a prospective, observational study conducted on 75 histopathologically proven patients of squamous cell carcinoma of Head and Neck (H&N), who came to the Department of Radiation Oncology, Gandhi Medical College and Hamidia Hospital, Bhopal from January to December 2015. Standard protocol based chemotherapy containing highly emetogenic cisplatin based chemotherapy was administered to all the patients. For prevention of delayed chemotherapy induced nausea and vomiting all patients were prescribed oral 5-HT3 antagonists. Oral Ondansetron 4mg TDS was given to cohort 1, oral Granisetron 1 mg BD to cohort2 and oral Palanosetron 0.5mg OD was given to cohort 3. They were graded as complete response when they did not have complains of nausea and vomiting.Results: In Ondansetron, Granisetron and in Palanosetron cohort 29%, 53% and 98% patients had complete response.Conclusions: Palanosetron appears superior. Our study was conducted on handfull of patients and compared palanosetron against only two 5-HT3 receptor antagonists, so a larger study is suggested to establish the efficacy and better response of palanosetron.

Inherited 5-oxoprolinase (OPLAH) deficiency is a rare inborn condition characterised by 5-oxoprolinuria. To date, three OPLAH mutations have been described: p.H870Pfs in a homozygous state, which results in a truncated protein, was reported in two siblings, and two heterozygous missense changes, p.S323R and p.V1089I, were independently identified in two unrelated patients. We describe the clinical context of a young girl who manifested 5-oxoprolinuria together with dusky episodes and who is compound heterozygote for two novel OPLAH variations: p.G860R and p.D1241V. To gain insight into the aetiology of the 5-oxoprolinase deficiency, we investigated the pathogenicity of all the reported missense mutations in the OPLAH gene. A yeast in vivo growth assay revealed that only p.S323R, p.G860R and p.D1241V affected the activity of the enzyme. Conclusion: Taken together, this report further suggests that hereditary 5-oxoprolinase deficiency is a benign biochemical condition caused by mutations in the OPLAH gene, which are transmitted in an autosomal recessive manner, but 5-oxoprolinuria may be a chance association in other disorders.