Showing papers by "Himanshu Kumar published in 2021"
TL;DR: Time point meta-analysis and gene set enrichment analyses revealed that common pathways are activated and suppressed in all three coronaviruses and a drug repurposing analysis was performed to identify potential drug candidates for combating COVID-19.
27 citations
TL;DR: In this paper, the authors used nonpathogenic mycobacterial species BCG as a model for Mtb infection to gain molecular insights and outcomes of this phenomenon, showing that BCG infection in PBMCs and THP-1 macrophages induce mitophagy and glycolysis, leading to differentiation of naive macrophage to M1 phenotype.
14 citations
TL;DR: In this article, the authors proposed miR-30e-5p as a therapeutic candidate in host-directed therapies (HDTs) upon bacterial infection by targeting key negative regulators such as SOCS1 and SOCS3 of innate immune signaling pathways.
Abstract: Host innate immunity is the major player against continuous microbial infection. Various pathogenic bacteria adopt the strategies to evade the immunity and show resistance towards the various established therapies. Despite the advent of many antibiotics for bacterial infections, there is a substantial need for the host-directed therapies (HDTs) to combat the infection. HDTs are recently being adopted to be useful in eradicating intracellular bacterial infection. Changing the innate immune responses of the host cells alters pathogen’s ability to reside inside the cell. MicroRNAs are the small non-coding endogenous molecules and post-transcriptional regulators to target the 3’UTR of the messenger RNA. They are reported to modulate the host’s immune responses during bacterial infections. Exploiting microRNAs as a therapeutic candidate in HDTs upon bacterial infection is still in its infancy. Here, initially, we re-analyzed the publicly available transcriptomic dataset of macrophages, infected with different pathogenic bacteria and identified significant genes and microRNAs common to the differential infections. We thus identified and miR-30e-5p, to be upregulated in different bacterial infections which enhances innate immunity to combat bacterial replication by targeting key negative regulators such as SOCS1 and SOCS3 of innate immune signaling pathways. Therefore, we propose miR-30e-5p as one of the potential candidates to be considered for additional clinical validation towards HDTs.
7 citations
TL;DR: Through extensive spectroscopic and computational studies, the factors controlling near-quantitative photoisomerization in both the directions (bistability) and the thermal stability of the metastable states are envisaged.
Abstract: Light-responsive molecular systems with multiple photoswitches in C3 -symmetric designs have enormous application potential. The design part of such molecular systems is critical due to its influence in several properties associated with the photoswitches. In order to tune, and in the evaluation of the design-property relationship, we synthesized 18 tripodal systems with variations in the core, linkers, connectivity, and azo(hetero)arene photoswitches. Through extensive spectroscopic and computational studies, we envisaged the factors controlling near-quantitative photoisomerization in both the directions (bistability) and the thermal stability of the metastable states. Furthermore, we also evaluated the impact of designs in obtaining reversible photo-responsive sol-gel phase transitions, solvatochromism, photo- and thermochromism.
6 citations
TL;DR: In this paper, the authors used RNA-seq based approach to find that the point mutation Irf8R294C does not affect pDC development, but it leads to defective type I IFN production, thus resulting in inefficient antiviral response.
Abstract: Plasmacytoid dendritic cells (pDCs) are the key producers of type I interferons (IFNs), thus playing central role in initiating antiviral immune response. Besides robust type I IFN production, pDCs also act as antigen presenting cells post immunogenic stimulation. Transcription factor Irf8 is indispensable for development of both pDC and cDC1 subset. However, the mechanism underlying the differential regulation by IRF8 in cDC1 and pDC specific genomic architecture of developmental pathways still remains to be fully elucidated. Previous studies indicated that, the Irf8R294C mutation specifically abrogates development of cDC1 without affecting that of pDC. In present study using RNA-seq based approach, we have found that though the point mutation Irf8R294C does not affect pDC development, it leads to defective type I IFN production, thus resulting in inefficient antiviral response. This observation unravels the distinctive roles of IRF8 in these two subpopulations- regulating the development of cDC1 whereas modulating the functionality of pDCs without affecting development. We report here, Irf8R294C mutation also causes defect in production of ISGs, prevents pDC activation in response to NDV infection (or CpG stimulation). Through in vivo studies, we demonstrate that abrogation of type I IFN production was concomitant with absence of pDC activation and increased NDV burden in IRF8R294C mice in comparison with wild type indicating inefficient viral clearance. Further we have also shown that Irf8R294C mutation abolishes the activation of type I IFN promoter by IRF8 justifying the low level of type I IFN production. Taken together, our study signifies that the single point mutation in Irf8, Irf8R294C severely compromises type I IFN mediated immune response by pDCs, thereby causing impairment in antiviral immunity.
2 citations
TL;DR: In this article, a cytosolic DNA sensor IFI16 is found to be essential for the activation of programmed cell death pathways in IAV infected cells, and the activation triggers the production of type I, III interferons, and also other pro-inflammatory cytokines via the STING-TBK1 and Pro-caspase-1 signaling axis, thereby promoting cell death.
Abstract: Programmed cell death pathways are triggered by various stresses or stimuli, including viral infections. The mechanism underlying the regulation of these pathways upon Influenza A virus IAV infection is not well characterized. We report that a cytosolic DNA sensor IFI16 is essential for the activation of programmed cell death pathways in IAV infected cells. We have identified that IFI16 functions as an RNA sensor for influenza A virus by binding to genomic RNA. The activation of IFI16 triggers the production of type I, III interferons, and also other pro-inflammatory cytokines via the STING-TBK1 and Pro-caspase-1 signaling axis, thereby promoting cell death (apoptosis and pyroptosis in IAV infected cells). Whereas, IFI16 knockdown cells showed reduced inflammatory responses and also prevented cell mortality during IAV infection. These results demonstrate the pivotal role of IFI16-mediated IAV sensing and its essential role in activating programmed cell death pathways.
TL;DR: Host immunity ensures protection against a foreign intrusion having the potential to disrupt the physiological balances of the host as discussed by the authors, which is a first line of defense and is instrumental in defending against intrusions.
Abstract: Host immunity ensures protection against a foreign intrusion having the potential to disrupt the physiological balances of the host. Innate immunity is a first line of defense and is instrumental i...
TL;DR: In this article, the authors discuss the anesthesia plan for a seven-year-old boy who underwent surgery for tongue-tie release and discuss the pathology of unilateral anotia and ipsilateral Bell's palsy.
Abstract: The inherited disease of unilateral anotia and ipsilateral Bell's palsy is exceedingly uncommon, but it has a few other clinical manifestations The prevalence of anotia in combination with congenital Bell's palsy is well-known by Berry-Treacher Collins and Goldenhar syndrome Despite the prevalence of anotia in combination with Bell's palsy, there have been relatively very few case reports about the corresponding conditions in India The aim of the paper is to discuss the anesthesia plan for a seven-year-old boy who underwent surgery for tongue-tie release