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Pravat Thatoi

Publications and source records attributed to Pravat Thatoi.

2 recordsLinked to original sources

Meta-analysis reveals pathway signature of Septic Shock

Septic shock is a major medical problem with high morbidity and mortality and incompletely understood biology. Availability of genome-wide expression data from different studies on septic shock empowers the quest for hitherto unidentified pathways by integration and meta-analysis of multiple data sets. Electronic search was performed on medical literature and gene expression databases. Selection of studies was based on the organism (human subjects), tissue of origin (circulating leukocytes) and the platform technology (gene expression microarray). Gene-level meta-analysis was conducted on the six selected studies to identify the genes consistently differentially expressed in septic shock. These genes were then subjected to pathway analysis. The identified up-regulated pathway hsa04380 (Osteoclast Differentiation) was validated in an independent cohort of patients. A simplified model was generated showing the major gene-modules dysregulated in SS.

Genomics

A novel polymorphism in nitric oxide synthase interacting protein (NOSIP) modulates nitric oxide synthesis and influences mortality in human sepsis

Nitric oxide, synthesised by three isoforms of Nitric Oxide synthases viz., nNOS by neurons, eNOS by endothelial cells and iNOS by phagocytes, performs a wide variety of biological functions in neurons, vascular endothelial cells and immune cells. Interaction between inducible nitric oxide synthase (iNOS) and Nitric oxide synthase interacting protein (NOSIP) was observed both in human monocytes and mouse macrophages and in cell free systems by biophysical methods. A novel mutation in nitric oxide synthase interacting protein (NOSIP) determined NO levels produced by human monocytes and was associated with disease severity in Sepsis patients. The study reveals NOSIP as an important regulator of inflammation by virtue of its ability to influence nitric oxide production both in mice and in humans and opens up novel avenues for therapeutic strategies against acute inflammation. While the influence of this novel NOSIP polymorphism in cardio-vascular and neuronal functions could be a subject of future investigations, its role in determining disease severity and mortality of the ongoing Covid 19 pandemic will be of immediate relevance.

Immunology