Ritobrata Goswami - Academia.edu (original) (raw)
Papers by Ritobrata Goswami
Frontiers Research Topics, 2020
Helper T cells play a critical role in the induction of tissue inflammation in immunity and autoi... more Helper T cells play a critical role in the induction of tissue inflammation in immunity and autoimmunity. Various subsets of T cells such as Th1, Th2, Th9 and Th17 cells have been shown to play a key role in the induction of tissue inflammation in allergic and organ-specific autoimmune inflammation. On the other hand, regulatory cells such as Foxp3+Tregs and Tr1 cells are essential to control functions of effector T cells and maintain tissue homeostasis. Distinct transcriptional and molecular pathways have been identified for the generation of various effector and regulatory T cells. Emerging molecular signatures of these effectors and of regulatory T cells indicate plasticity in their developmental pathways, which is dictated by the tissue microenvironment and by other factors including cytokines and transcription factors
Dalton Transactions
Two new paths for coordination driven self-assembly reactions under the binding supports of 2-((1... more Two new paths for coordination driven self-assembly reactions under the binding supports of 2-((1-hydroxy-2-methylpropan-2-ylimino)methyl)-6-methoxyphenol (H2L) have been discovered from reactions of Cu(ClO4)2·6H2O, NEt3 and GdCl3/DyCl3·6H2O in MeOH/CHCl3 (2:1) medium. Similar...
Environmental Science and Pollution Research
The Journal of Immunology
IL-9-secreting Th9 cells are generated when naïve CD4+ T cells are cultured with IL-4 and TGF-β.... more IL-9-secreting Th9 cells are generated when naïve CD4+ T cells are cultured with IL-4 and TGF-β. The transcription factor, PU.1 is required for the development of Th9 cells. The expression of PU.1, which is abundantly expressed in Th9 cells, is dependent on TGF-β dose. Dose dependent increase in TGF-β leads to a concomitant increase in PU.1 expression and IL-9 production. Ectopic expression of PU.1 can convert Th2 cells to Th9 phenotype and enhance IL-9 production from Th9 cells. The DNA binding domain and the transactivation domains of PU.1 are required for PU.1 to activate Il9, suggesting that as it binds Il9, it recruits other factors to mediate gene activation. We hypothesized that PU.1 recruits specific chromatin modifying enzymes to the Il9 locus. H3 acetylation is decreased in PU.1-deficient Th9 cells on both the Il9 promoter and a second conserved non-coding sequence immediately after 3’ of the Il9 gene. H3K9/18 acetylation is also diminished in PU.1-deficient Th9 cells whi...
The Journal of Immunology
The TNF family cytokine TL1A (Tnfsf15) costimulates T cells through its receptor DR3 (Tnfrsf25). ... more The TNF family cytokine TL1A (Tnfsf15) costimulates T cells through its receptor DR3 (Tnfrsf25). Currently known effects of TL1A on T cell differentiation or systemic immune responses cannot account for the resistance of Tnfrsf25-/- mice to diverse animal models of autoimmune and allergic inflammation. IL-9 is a cytokine that promotes inflammatory and allergic immune responses and is expressed by a distinct subset of T cells early after T cell activation or restimulation. We have found that TL1A potently promotes generation of T cells producing IL-9 (Th9) by signaling through DR3 in a cell-intrinsic manner. Unlike the TNF family member OX40 ligand, TL1A increases Th9 differentiation independently of STAT6 and the TNF-signaling adaptor TRAF6. Instead, TL1A affects Th9 differentiation through enhancing IL-2-dependent STAT5 activation and allowing increased binding to the IL-9 promoter. In two models of allergic asthma, we demonstrate that Tnfrsf25-/- mice have reduced disease severity...
Environmental Nanotechnology, Monitoring & Management
Cytokines are extracellular proteins that mediate communication between cells. T helper cell subs... more Cytokines are extracellular proteins that mediate communication between cells. T helper cell subsets secrete specific cytokines that promote the development of inflammation. Naïve CD4+ T cells activated and primed in the presence of TGF-β and IL-4 predominantly secrete IL-9, a cytokine that acts as a growth factor for T cells and mast cells, and promotes allergic inflammation. The transcription factors downstream of TGF-β- and IL-4-induced signaling, and that are required for expression of IL-9, have not been previously examined. IL-4 signaling induces the expression of IRF4, a transcription factor required for the development of Th9 cells. IL-4 and the downstream-activated factor STAT6 also interfere with the expression of the transcription factors T-bet and Foxp3 that inhibit IL-9 production from Th9 cells. The TGF-β pathway induces the expression of PU.1, another transcription factor required for Th9 development. In the absence of PU.1 there is increased association of a subset o...
Inflammation Research, 2022
Background The mayhem COVID-19 that was ushered by the severe acute respiratory syndrome coronavi... more Background The mayhem COVID-19 that was ushered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) was declared pandemic by the World Health Organization in March 2020. Since its initial outbreak in late 2019, the virus has affected hundreds of million adults in the world and killing millions in the process. After the approval of newly developed vaccines, severe challenges remain to manufacture and administer them to the adult population globally in quick time. However, we have witnessed several mutations of the virus leading to 'waves' of viral spread and mortality. WHO has categorized these mutations as variants of concern (VOCs) and variants of interest (VOIs). The mortality due to COVID-19 has also been associated with various comorbidities and improper immune response. This has created further complications in understanding the nature of the SARS-CoV2-host interaction that has fuelled doubts in the efficacy of the approved vaccines. Whether there is requirement of booster dose and whether the impending wave could affect the children are some of the hotly debated topics. Materials and Methods A systematic literature review of PubMed, Medline, Scopus, Google Scholar was utilized to understand the nature of Delta variant and how it alters our T-cell responses and cytokine production and neutralizes vaccinegenerated antibodies. Conclusion In this review, we discuss the variants of SARS-CoV2 with specific focus on the Delta variant. We also specifically review the T-cell response against the virus and bring a narrative of various factors that may hold the key to fight against this marauding virus.
JAK-STAT Signaling in Diseases, 2020
Methods in molecular biology, 2017
Since the discovery of IL-9 almost three decades back as a growth factor, we have come a long way... more Since the discovery of IL-9 almost three decades back as a growth factor, we have come a long way to understand its pleiotropic functions in the immune system. Despite its many functions, IL-9 still remains as an understudied cytokine. In the last decade, renewed emphasis has been provided to understand the biology of IL-9. Any growth factor or cytokine signals via its cognate receptor to mediate biological functions. In this chapter, we discuss the IL-9 signal transduction in different cell types, which would then exert its distinct functions.
International Review of Cell and Molecular Biology, 2017
The Jak-STAT pathway is one of many pleiotropic signaling pathways that plays an important role i... more The Jak-STAT pathway is one of many pleiotropic signaling pathways that plays an important role in organismal development and in response to changing environmental cues. As a key signaling cascade for cytokines and growth factors, Jak-STAT plays central role in the innate and adaptive immune system. Cytokines control the stability, commitment, and maturation of cytotoxic and helper T cells, parts of the adaptive immune system that mediate immunity to pathogens and are linked to inflammatory diseases. Dysregulation of Jak-STAT protein expression or function leads to autoimmunity, allergic diseases, and cancer. Because of their central role in these responses, Jak and STAT molecules have been targeted to develop therapeutics. This review extensively discusses the mechanism of how Jak-STAT signaling in T cells defines our immune responses in the battle against foreign pathogens.
We developed a piecewise isothermal nucleic acid test (PINAT) as a platform technology for diagno... more We developed a piecewise isothermal nucleic acid test (PINAT) as a platform technology for diagnosing pathogen-associated infections, empowered by an illustrative novel methodology that embeds an exclusive DNA-mediated specific probing reaction with the backbone of an isothermal reverse transcription cum amplification protocol for detecting viral RNA. In a point-of-care format, this test is executable in a unified single-step, single-chamber procedure, leading to seamless sample-to-result integration in an inexpensive, scalable, pre-programmable, and customizable portable device, with mobile-app-integrated interpretation and analytics involving minimal manually operative procedures. The test exhibited a high sensitivity and specificity of detection when assessed using 200 double-blind patient samples for detecting SARS-CoV-2 infection by the Indian Council of Medical Research (ICMR), and subsequently using 170 double-blind patient samples in a point-of-care format outside controlled laboratory settings as performed by unskilled technicians in an organized clinical trial. We also established its efficacy in detecting Influenza A infection by performing the diagnosis at the point of collection with uncompromised detection rigor. The envisaged trade-off between advanced laboratory-based molecular diagnostic procedures and the elegance of common rapid tests renders the method ideal for deployment in resource-limited settings towards catering the needs of the underserved.
We report a novel piece-wise isothermal nucleic acid test (PINAT) for diagnosing pathogen-associa... more We report a novel piece-wise isothermal nucleic acid test (PINAT) for diagnosing pathogen-associated RNA that embeds an exclusive DNA-mediated specific probing reaction with the backbone of an isothermal reverse-transcription cum amplification protocol as a unified single-step procedure. This single step sample-to-result test method has been seamlessly integrated in an inexpensive, scalable, pre-programmable and portable instrument, resulting in a generic platform technology for detecting nucleic acid from a wide variety of pathogens. The test exhibited high sensitivity and specificity of detection when assessed using 200 double-blind patient samples for detecting SARS-CoV-2 infection conducted by the Indian Council of Medical Research (ICMR), reporting a positive and negative percent agreement of 94.6% and 98% respectively. We also established its efficacy in detecting influenza-A infection, performing the diagnosis at the point of collection with uncompromised detection rigor. The...
The Journal of Immunology, 2020
Vitamin D can modulate the innate and adaptive immune system. Vitamin D deficiency has been assoc... more Vitamin D can modulate the innate and adaptive immune system. Vitamin D deficiency has been associated with various autoimmune diseases. Th9 cells are implicated in the pathogenesis of numerous autoimmune diseases. Thus, we investigated the role of calcitriol (active metabolite of vitamin D) in the regulation of Th9 cell differentiation. In this study, we have unraveled the molecular mechanisms of calcitriol-mediated regulation of Th9 cell differentiation. Calcitriol significantly diminished IL-9 secretion from murine Th9 cells associated with downregulated expression of the Th9-associated transcription factor, PU.1. Ectopic expression of VDR in Th9 cells attenuated the percentage of IL-9–secreting cells. VDR associated with PU.1 in Th9 cells. Using a series of mutations, we were able to dissect the VDR domain involved in the regulation of the Il9 gene. The VDR–PU.1 interaction prevented the accessibility of PU.1 to the Il9 gene promoter, thereby restricting its expression. However,...
The Journal of Nutritional Biochemistry, 2021
Distinct T helper cells, including Th9 cells help maintain homeostasis in the immune system. Vita... more Distinct T helper cells, including Th9 cells help maintain homeostasis in the immune system. Vitamins play pivotal role in the immune system through many mechanisms, including regulating the differentiation of T helper cells. Calcitriol (1,25-dihydroxyvitamin D3) and retinoic acid possess hormone-like properties and are the bioactive metabolites of vitamin D and A, respectively, that signal through heterodimers containing the common retinoid X receptor. In contrast to individual treatment with the vitamins that significantly attenuates IL-9 production from Th9 cells, Th9 cells treated with both vitamins demonstrated IL-9 production similar to untreated Th9 cells. This is associated with reciprocal expression of PU.1 and Foxp3. While the recruitment of PU.1 was significantly impaired to the Il9 gene in the presence of calcitriol or retinoic acid in Th9 cells, addition of both vitamins together increased the recruitment of PU.1 to the Il9 gene. Calcitriol and retinoic acid together impaired the recruitment of HDAC1 to the Il9 gene without impacting Gcn5 recruitment. Importantly, retinoic acid negated the effect of calcitriol and impaired the binding of VDR on the Il9 gene by dampened VDR-RXR formation. Collectively, our data show that calcitriol and retinoic acid antagonize each other to regulate the differentiation of Th9 cells.
World Journal of Microbiology and Biotechnology, 2020
Microbial infections have become a global threat to drug-tolerant phenomena due to their biofilm ... more Microbial infections have become a global threat to drug-tolerant phenomena due to their biofilm formatting capacity. In many cases, conventional antimicrobial drugs fail to combat the infection, thus necessitating the discovery of some alternative medicine. Over several decades, plant metabolites have played a critical role in treating a broad spectrum of microbial infections due to its low cytotoxicity. Andrograpanin, a secondary metabolite, is a diterpenoid present in the leaf of Andrographis paniculata. In this study, andrograpanin (0.15 mM) exhibited significant inhibition on biofilm production by Pseudomonas aeruginosa in the presence of gentamicin (0.0084 mM). The impaired production of extracellular polymeric substances and several virulence factors of Pseudomonas aeruginosa were investigated to understand the mechanism of action mediated by andrograpanin. The structural alteration of biofilm was evaluated by using fluorescence microscopy, atomic force microscopy and field emission scanning electron microscopy. The in silico molecular simulation studies predicted interaction of andrograpanin with quorum sensing proteins such as RhlI, LasI, LasR, and swarming motility protein BswR of Pseudomonas aeruginosa. Overall the studies indicate that andrograpanin could be used as a therapeutic molecule against biofilm development by Pseudomonas aeruginosa.
Gene Reports, 2021
Abstract 17β-estradiol (E2) or the bioactive form of estrogen has wide range of impact in regulat... more Abstract 17β-estradiol (E2) or the bioactive form of estrogen has wide range of impact in regulating human physiology. It not only regulates organ development but also controls immune responses. E2 impacts the recruitment of immune cells to endothelium by regulating the expression of pattern recognition receptors. As endothelium is central to human physiology, it becomes a good target for many cancer and cardiovascular diseases. A broad range of genes get dysregulated during the course of pathophysiological events and many of them are regulated via E2 signalling. Recent evidence shows that E2 regulate the expression of many endothelial cell specific microRNAs (EC-miRNA), thereby affecting expression and stability of many factors including estrogen receptor alpha. In this study, we analysed two distinct datasets of different endothelial cell models to discern a set of genes that potentially play very crucial role in regulating general physiological as well as pathophysiological events. GEO2R and Cytoscape were used to analyze the datasets GSE51535 and GSE16683. DAVID and ClueGO functional annotation of the genes revealed association with genetically associated disease classes such as cancer and cardiovascular. KEGG pathways, Reactome pathways and Wiki-pathways were used for pathway enrichment analysis. One of the enriched pathways includes the synthesis of pri-miRNA by RNA polymerase II. Endothelial cell specific miRNA and target gene association revealed key miRNAs and their involvement in regulatory pathways. Overall, our study highlights the complexity of miRNA mediated E2 regulation of genes in endothelial cells and provides potential target genes for therapeutics in cancer and cardiovascular pathophysiological conditions.
Meta Gene, 2021
Abstract Introduction 1,25(OH)2D3 or calcitriol (active form of vitamin D) is a known immunomodul... more Abstract Introduction 1,25(OH)2D3 or calcitriol (active form of vitamin D) is a known immunomodulatory vitamin. 1,25(OH)2D3 impacts the regulation of multiple immune cell types including monocytes. Monocytes play important role in regulating viral infections and inflammation. Aberrant regulation of monocytes is associated with various inflammatory disorders including neurological disorders. Objectives The primary objective of this study was to find out the impact of vitamin D in monocytic gene expressions and how it affects disease development and pathogenesis. Methodology A bioinformatics workflow incorporating pathway analysis using KEGG and GAD disease was employed to collate each set of gene expression data. In Cytoscape, STRING was utilized to determine protein-protein interactions and data analysis. ClueGo was used to show association between diseases. Results 1,25(OH)2D3-mediated regulation includes genes associated with transport and surface markers. A significant association of 1,25(OH)2D3 with mitochondrial genes was observed in HIV, Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). We also observed a majority of the shared genes between the neurodegenerative (ND) disorders and HIV, are also associated with aging. From literature review we found out that positively expressed genes upon vitamin D treatment, have a neuroprotective as well as an anti-aging role. Conclusion Overall, the pathway analysis indicates immunomodulatory function of 1,25(OH)2D3 in regulating HIV and neuroinflammation; augments the mitochondrial theory in aging. It also indicates towards a possible neuroprotective and anti-aging role of vitamin D via monocytes.
Frontiers Research Topics, 2020
Helper T cells play a critical role in the induction of tissue inflammation in immunity and autoi... more Helper T cells play a critical role in the induction of tissue inflammation in immunity and autoimmunity. Various subsets of T cells such as Th1, Th2, Th9 and Th17 cells have been shown to play a key role in the induction of tissue inflammation in allergic and organ-specific autoimmune inflammation. On the other hand, regulatory cells such as Foxp3+Tregs and Tr1 cells are essential to control functions of effector T cells and maintain tissue homeostasis. Distinct transcriptional and molecular pathways have been identified for the generation of various effector and regulatory T cells. Emerging molecular signatures of these effectors and of regulatory T cells indicate plasticity in their developmental pathways, which is dictated by the tissue microenvironment and by other factors including cytokines and transcription factors
Dalton Transactions
Two new paths for coordination driven self-assembly reactions under the binding supports of 2-((1... more Two new paths for coordination driven self-assembly reactions under the binding supports of 2-((1-hydroxy-2-methylpropan-2-ylimino)methyl)-6-methoxyphenol (H2L) have been discovered from reactions of Cu(ClO4)2·6H2O, NEt3 and GdCl3/DyCl3·6H2O in MeOH/CHCl3 (2:1) medium. Similar...
Environmental Science and Pollution Research
The Journal of Immunology
IL-9-secreting Th9 cells are generated when naïve CD4+ T cells are cultured with IL-4 and TGF-β.... more IL-9-secreting Th9 cells are generated when naïve CD4+ T cells are cultured with IL-4 and TGF-β. The transcription factor, PU.1 is required for the development of Th9 cells. The expression of PU.1, which is abundantly expressed in Th9 cells, is dependent on TGF-β dose. Dose dependent increase in TGF-β leads to a concomitant increase in PU.1 expression and IL-9 production. Ectopic expression of PU.1 can convert Th2 cells to Th9 phenotype and enhance IL-9 production from Th9 cells. The DNA binding domain and the transactivation domains of PU.1 are required for PU.1 to activate Il9, suggesting that as it binds Il9, it recruits other factors to mediate gene activation. We hypothesized that PU.1 recruits specific chromatin modifying enzymes to the Il9 locus. H3 acetylation is decreased in PU.1-deficient Th9 cells on both the Il9 promoter and a second conserved non-coding sequence immediately after 3’ of the Il9 gene. H3K9/18 acetylation is also diminished in PU.1-deficient Th9 cells whi...
The Journal of Immunology
The TNF family cytokine TL1A (Tnfsf15) costimulates T cells through its receptor DR3 (Tnfrsf25). ... more The TNF family cytokine TL1A (Tnfsf15) costimulates T cells through its receptor DR3 (Tnfrsf25). Currently known effects of TL1A on T cell differentiation or systemic immune responses cannot account for the resistance of Tnfrsf25-/- mice to diverse animal models of autoimmune and allergic inflammation. IL-9 is a cytokine that promotes inflammatory and allergic immune responses and is expressed by a distinct subset of T cells early after T cell activation or restimulation. We have found that TL1A potently promotes generation of T cells producing IL-9 (Th9) by signaling through DR3 in a cell-intrinsic manner. Unlike the TNF family member OX40 ligand, TL1A increases Th9 differentiation independently of STAT6 and the TNF-signaling adaptor TRAF6. Instead, TL1A affects Th9 differentiation through enhancing IL-2-dependent STAT5 activation and allowing increased binding to the IL-9 promoter. In two models of allergic asthma, we demonstrate that Tnfrsf25-/- mice have reduced disease severity...
Environmental Nanotechnology, Monitoring & Management
Cytokines are extracellular proteins that mediate communication between cells. T helper cell subs... more Cytokines are extracellular proteins that mediate communication between cells. T helper cell subsets secrete specific cytokines that promote the development of inflammation. Naïve CD4+ T cells activated and primed in the presence of TGF-β and IL-4 predominantly secrete IL-9, a cytokine that acts as a growth factor for T cells and mast cells, and promotes allergic inflammation. The transcription factors downstream of TGF-β- and IL-4-induced signaling, and that are required for expression of IL-9, have not been previously examined. IL-4 signaling induces the expression of IRF4, a transcription factor required for the development of Th9 cells. IL-4 and the downstream-activated factor STAT6 also interfere with the expression of the transcription factors T-bet and Foxp3 that inhibit IL-9 production from Th9 cells. The TGF-β pathway induces the expression of PU.1, another transcription factor required for Th9 development. In the absence of PU.1 there is increased association of a subset o...
Inflammation Research, 2022
Background The mayhem COVID-19 that was ushered by the severe acute respiratory syndrome coronavi... more Background The mayhem COVID-19 that was ushered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) was declared pandemic by the World Health Organization in March 2020. Since its initial outbreak in late 2019, the virus has affected hundreds of million adults in the world and killing millions in the process. After the approval of newly developed vaccines, severe challenges remain to manufacture and administer them to the adult population globally in quick time. However, we have witnessed several mutations of the virus leading to 'waves' of viral spread and mortality. WHO has categorized these mutations as variants of concern (VOCs) and variants of interest (VOIs). The mortality due to COVID-19 has also been associated with various comorbidities and improper immune response. This has created further complications in understanding the nature of the SARS-CoV2-host interaction that has fuelled doubts in the efficacy of the approved vaccines. Whether there is requirement of booster dose and whether the impending wave could affect the children are some of the hotly debated topics. Materials and Methods A systematic literature review of PubMed, Medline, Scopus, Google Scholar was utilized to understand the nature of Delta variant and how it alters our T-cell responses and cytokine production and neutralizes vaccinegenerated antibodies. Conclusion In this review, we discuss the variants of SARS-CoV2 with specific focus on the Delta variant. We also specifically review the T-cell response against the virus and bring a narrative of various factors that may hold the key to fight against this marauding virus.
JAK-STAT Signaling in Diseases, 2020
Methods in molecular biology, 2017
Since the discovery of IL-9 almost three decades back as a growth factor, we have come a long way... more Since the discovery of IL-9 almost three decades back as a growth factor, we have come a long way to understand its pleiotropic functions in the immune system. Despite its many functions, IL-9 still remains as an understudied cytokine. In the last decade, renewed emphasis has been provided to understand the biology of IL-9. Any growth factor or cytokine signals via its cognate receptor to mediate biological functions. In this chapter, we discuss the IL-9 signal transduction in different cell types, which would then exert its distinct functions.
International Review of Cell and Molecular Biology, 2017
The Jak-STAT pathway is one of many pleiotropic signaling pathways that plays an important role i... more The Jak-STAT pathway is one of many pleiotropic signaling pathways that plays an important role in organismal development and in response to changing environmental cues. As a key signaling cascade for cytokines and growth factors, Jak-STAT plays central role in the innate and adaptive immune system. Cytokines control the stability, commitment, and maturation of cytotoxic and helper T cells, parts of the adaptive immune system that mediate immunity to pathogens and are linked to inflammatory diseases. Dysregulation of Jak-STAT protein expression or function leads to autoimmunity, allergic diseases, and cancer. Because of their central role in these responses, Jak and STAT molecules have been targeted to develop therapeutics. This review extensively discusses the mechanism of how Jak-STAT signaling in T cells defines our immune responses in the battle against foreign pathogens.
We developed a piecewise isothermal nucleic acid test (PINAT) as a platform technology for diagno... more We developed a piecewise isothermal nucleic acid test (PINAT) as a platform technology for diagnosing pathogen-associated infections, empowered by an illustrative novel methodology that embeds an exclusive DNA-mediated specific probing reaction with the backbone of an isothermal reverse transcription cum amplification protocol for detecting viral RNA. In a point-of-care format, this test is executable in a unified single-step, single-chamber procedure, leading to seamless sample-to-result integration in an inexpensive, scalable, pre-programmable, and customizable portable device, with mobile-app-integrated interpretation and analytics involving minimal manually operative procedures. The test exhibited a high sensitivity and specificity of detection when assessed using 200 double-blind patient samples for detecting SARS-CoV-2 infection by the Indian Council of Medical Research (ICMR), and subsequently using 170 double-blind patient samples in a point-of-care format outside controlled laboratory settings as performed by unskilled technicians in an organized clinical trial. We also established its efficacy in detecting Influenza A infection by performing the diagnosis at the point of collection with uncompromised detection rigor. The envisaged trade-off between advanced laboratory-based molecular diagnostic procedures and the elegance of common rapid tests renders the method ideal for deployment in resource-limited settings towards catering the needs of the underserved.
We report a novel piece-wise isothermal nucleic acid test (PINAT) for diagnosing pathogen-associa... more We report a novel piece-wise isothermal nucleic acid test (PINAT) for diagnosing pathogen-associated RNA that embeds an exclusive DNA-mediated specific probing reaction with the backbone of an isothermal reverse-transcription cum amplification protocol as a unified single-step procedure. This single step sample-to-result test method has been seamlessly integrated in an inexpensive, scalable, pre-programmable and portable instrument, resulting in a generic platform technology for detecting nucleic acid from a wide variety of pathogens. The test exhibited high sensitivity and specificity of detection when assessed using 200 double-blind patient samples for detecting SARS-CoV-2 infection conducted by the Indian Council of Medical Research (ICMR), reporting a positive and negative percent agreement of 94.6% and 98% respectively. We also established its efficacy in detecting influenza-A infection, performing the diagnosis at the point of collection with uncompromised detection rigor. The...
The Journal of Immunology, 2020
Vitamin D can modulate the innate and adaptive immune system. Vitamin D deficiency has been assoc... more Vitamin D can modulate the innate and adaptive immune system. Vitamin D deficiency has been associated with various autoimmune diseases. Th9 cells are implicated in the pathogenesis of numerous autoimmune diseases. Thus, we investigated the role of calcitriol (active metabolite of vitamin D) in the regulation of Th9 cell differentiation. In this study, we have unraveled the molecular mechanisms of calcitriol-mediated regulation of Th9 cell differentiation. Calcitriol significantly diminished IL-9 secretion from murine Th9 cells associated with downregulated expression of the Th9-associated transcription factor, PU.1. Ectopic expression of VDR in Th9 cells attenuated the percentage of IL-9–secreting cells. VDR associated with PU.1 in Th9 cells. Using a series of mutations, we were able to dissect the VDR domain involved in the regulation of the Il9 gene. The VDR–PU.1 interaction prevented the accessibility of PU.1 to the Il9 gene promoter, thereby restricting its expression. However,...
The Journal of Nutritional Biochemistry, 2021
Distinct T helper cells, including Th9 cells help maintain homeostasis in the immune system. Vita... more Distinct T helper cells, including Th9 cells help maintain homeostasis in the immune system. Vitamins play pivotal role in the immune system through many mechanisms, including regulating the differentiation of T helper cells. Calcitriol (1,25-dihydroxyvitamin D3) and retinoic acid possess hormone-like properties and are the bioactive metabolites of vitamin D and A, respectively, that signal through heterodimers containing the common retinoid X receptor. In contrast to individual treatment with the vitamins that significantly attenuates IL-9 production from Th9 cells, Th9 cells treated with both vitamins demonstrated IL-9 production similar to untreated Th9 cells. This is associated with reciprocal expression of PU.1 and Foxp3. While the recruitment of PU.1 was significantly impaired to the Il9 gene in the presence of calcitriol or retinoic acid in Th9 cells, addition of both vitamins together increased the recruitment of PU.1 to the Il9 gene. Calcitriol and retinoic acid together impaired the recruitment of HDAC1 to the Il9 gene without impacting Gcn5 recruitment. Importantly, retinoic acid negated the effect of calcitriol and impaired the binding of VDR on the Il9 gene by dampened VDR-RXR formation. Collectively, our data show that calcitriol and retinoic acid antagonize each other to regulate the differentiation of Th9 cells.
World Journal of Microbiology and Biotechnology, 2020
Microbial infections have become a global threat to drug-tolerant phenomena due to their biofilm ... more Microbial infections have become a global threat to drug-tolerant phenomena due to their biofilm formatting capacity. In many cases, conventional antimicrobial drugs fail to combat the infection, thus necessitating the discovery of some alternative medicine. Over several decades, plant metabolites have played a critical role in treating a broad spectrum of microbial infections due to its low cytotoxicity. Andrograpanin, a secondary metabolite, is a diterpenoid present in the leaf of Andrographis paniculata. In this study, andrograpanin (0.15 mM) exhibited significant inhibition on biofilm production by Pseudomonas aeruginosa in the presence of gentamicin (0.0084 mM). The impaired production of extracellular polymeric substances and several virulence factors of Pseudomonas aeruginosa were investigated to understand the mechanism of action mediated by andrograpanin. The structural alteration of biofilm was evaluated by using fluorescence microscopy, atomic force microscopy and field emission scanning electron microscopy. The in silico molecular simulation studies predicted interaction of andrograpanin with quorum sensing proteins such as RhlI, LasI, LasR, and swarming motility protein BswR of Pseudomonas aeruginosa. Overall the studies indicate that andrograpanin could be used as a therapeutic molecule against biofilm development by Pseudomonas aeruginosa.
Gene Reports, 2021
Abstract 17β-estradiol (E2) or the bioactive form of estrogen has wide range of impact in regulat... more Abstract 17β-estradiol (E2) or the bioactive form of estrogen has wide range of impact in regulating human physiology. It not only regulates organ development but also controls immune responses. E2 impacts the recruitment of immune cells to endothelium by regulating the expression of pattern recognition receptors. As endothelium is central to human physiology, it becomes a good target for many cancer and cardiovascular diseases. A broad range of genes get dysregulated during the course of pathophysiological events and many of them are regulated via E2 signalling. Recent evidence shows that E2 regulate the expression of many endothelial cell specific microRNAs (EC-miRNA), thereby affecting expression and stability of many factors including estrogen receptor alpha. In this study, we analysed two distinct datasets of different endothelial cell models to discern a set of genes that potentially play very crucial role in regulating general physiological as well as pathophysiological events. GEO2R and Cytoscape were used to analyze the datasets GSE51535 and GSE16683. DAVID and ClueGO functional annotation of the genes revealed association with genetically associated disease classes such as cancer and cardiovascular. KEGG pathways, Reactome pathways and Wiki-pathways were used for pathway enrichment analysis. One of the enriched pathways includes the synthesis of pri-miRNA by RNA polymerase II. Endothelial cell specific miRNA and target gene association revealed key miRNAs and their involvement in regulatory pathways. Overall, our study highlights the complexity of miRNA mediated E2 regulation of genes in endothelial cells and provides potential target genes for therapeutics in cancer and cardiovascular pathophysiological conditions.
Meta Gene, 2021
Abstract Introduction 1,25(OH)2D3 or calcitriol (active form of vitamin D) is a known immunomodul... more Abstract Introduction 1,25(OH)2D3 or calcitriol (active form of vitamin D) is a known immunomodulatory vitamin. 1,25(OH)2D3 impacts the regulation of multiple immune cell types including monocytes. Monocytes play important role in regulating viral infections and inflammation. Aberrant regulation of monocytes is associated with various inflammatory disorders including neurological disorders. Objectives The primary objective of this study was to find out the impact of vitamin D in monocytic gene expressions and how it affects disease development and pathogenesis. Methodology A bioinformatics workflow incorporating pathway analysis using KEGG and GAD disease was employed to collate each set of gene expression data. In Cytoscape, STRING was utilized to determine protein-protein interactions and data analysis. ClueGo was used to show association between diseases. Results 1,25(OH)2D3-mediated regulation includes genes associated with transport and surface markers. A significant association of 1,25(OH)2D3 with mitochondrial genes was observed in HIV, Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). We also observed a majority of the shared genes between the neurodegenerative (ND) disorders and HIV, are also associated with aging. From literature review we found out that positively expressed genes upon vitamin D treatment, have a neuroprotective as well as an anti-aging role. Conclusion Overall, the pathway analysis indicates immunomodulatory function of 1,25(OH)2D3 in regulating HIV and neuroinflammation; augments the mitochondrial theory in aging. It also indicates towards a possible neuroprotective and anti-aging role of vitamin D via monocytes.