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Article ; Online: Gut dysbiosis and metabolic diseases.

Bandopadhyay, Purbita / Ganguly, Dipyaman

Progress in molecular biology and translational science

2022 Volume 191, Issue 1, Page(s) 153–174

Abstract: Disruption in the composition of the gut microbial flora, the so-called gut dysbiosis, has been associated with and pathogenically implicated in a number of metabolic disorders such as type 2 diabetes mellitus, non-alcoholic fatty liver disease as well ... ...

Abstract	Disruption in the composition of the gut microbial flora, the so-called gut dysbiosis, has been associated with and pathogenically implicated in a number of metabolic disorders such as type 2 diabetes mellitus, non-alcoholic fatty liver disease as well as atherosclerosis. We describe the key finding in this domain in terms of the gut dysbiotic effects of obesogenic diets linked to metabolic dysregulations, the cross-talk between host genetics and gut ecology in preclinical models of metabolic syndrome as well as in humans, effect of circadian rhythm on gut microbiome, the regulation of systemic immunocellular response, participating in the metabolic disorder-associated systemic inflammation, by gut microbiome and metabolites derived from them. Finally, we collate the evidence gathered till date on specific gut dysbiotic features documented in different components of metabolic syndrome in humans. Understanding gut dysbiosis in metabolic syndrome offers new insights into the pathogenesis of the specific clinical contexts as well as provide potential new therapeutic targets that warrant further exploration.
MeSH term(s)	Humans ; Dysbiosis ; Metabolic Syndrome/complications ; Diabetes Mellitus, Type 2/complications ; Gastrointestinal Microbiome ; Metabolic Diseases
Language	English
Publishing date	2022-07-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2471995-X
ISSN	1878-0814 ; 0079-6603 ; 1877-1173
ISSN (online)	1878-0814
ISSN	0079-6603 ; 1877-1173
DOI	10.1016/bs.pmbts.2022.06.031
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Article ; Online: Suppressed transcript diversity and immune response in COVID-19 ICU patients: a longitudinal study.

Mehta, Priyanka / Chattopadhyay, Partha / Mohite, Ramakant / D'Rozario, Ranit / Bandopadhyay, Purbita / Sarif, Jafar / Ray, Yogiraj / Ganguly, Dipyaman / Pandey, Rajesh

Life science alliance

2023 Volume 7, Issue 1

Abstract: Understanding the dynamic changes in gene expression during Acute Respiratory Distress Syndrome (ARDS) progression in post-acute infection patients is crucial for unraveling the underlying mechanisms. Study investigates the longitudinal changes in gene/ ... ...

Abstract	Understanding the dynamic changes in gene expression during Acute Respiratory Distress Syndrome (ARDS) progression in post-acute infection patients is crucial for unraveling the underlying mechanisms. Study investigates the longitudinal changes in gene/transcript expression patterns in hospital-admitted severe COVID-19 patients with ARDS post-acute SARS-CoV-2 infection. Blood samples were collected at three time points and patients were stratified into severe and mild ARDS, based on their oxygenation saturation (SpO
MeSH term(s)	Humans ; COVID-19/genetics ; Longitudinal Studies ; Bayes Theorem ; SARS-CoV-2 ; Respiratory Distress Syndrome/genetics ; Immunity ; Intensive Care Units ; Disease Progression
Language	English
Publishing date	2023-11-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202302305
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Article ; Online: Mitochondrial sourcing of interferogenic ligands and an autoantigen in human obesity-associated metaflammation.

Ghosh, Amrit Raj / Bandopadhyay, Purbita / Sarkar, Jit / Khanna, Shashi / Chaudhuri, Tamonas / Tantia, Om / Chakrabarti, Partha / Ganguly, Dipyaman

Obesity (Silver Spring, Md.)

2023 Volume 31, Issue 9, Page(s) 2229–2234

Abstract: Objective: Visceral adipose tissue (VAT) inflammation contributes to metabolic dysregulation in obesity. VAT recruitment and activation of plasmacytoid dendritic cells (pDCs) through toll-like receptor 9 (TLR9) recognition of self-DNA, leading to ... ...

Abstract	Objective: Visceral adipose tissue (VAT) inflammation contributes to metabolic dysregulation in obesity. VAT recruitment and activation of plasmacytoid dendritic cells (pDCs) through toll-like receptor 9 (TLR9) recognition of self-DNA, leading to induction of type I interferons, are crucial innate triggers for this VAT inflammation. It was hypothesized that mitochondrial DNA (mtDNA) can contribute to TLR9 activation in VAT-recruited pDCs in obesity, and this study aimed to identify the carrier protein for ligand access to TLR9 and to explore whether this also provides for a source of autoantigens in this context. Methods: VAT samples, used for gene expression studies as well as adipose explant cultures, were collected from patients with obesity (n = 54) and lean patients (n = 10). Supernatants from human pDC cultures, treated with adipose explant culture supernatants, were used for interferon α ELISA. Venous plasma, from patients with (n = 114) and without (n = 45) obesity, was used for an ELISA for autoantibodies. Results: MtDNA from VAT in obesity, in complex with mitochondrial transcription factor A protein (TFAM), acts as interferogenic ligands for pDCs. Humoral autoreactivity against TFAM is also induced in obesity. Conclusions: Interferogenic ligands and an autoantigen can be sourced from dysfunctional mitochondria in VAT of humans with obesity. Further therapeutic and prognostic potential for this immune mechanism in obesity warrants exploration.
MeSH term(s)	Humans ; Toll-Like Receptor 9/genetics ; Toll-Like Receptor 9/metabolism ; Ligands ; Autoantigens/metabolism ; Obesity/metabolism ; Inflammation/metabolism ; Mitochondria/metabolism ; DNA, Mitochondrial/metabolism ; Dendritic Cells/metabolism
Chemical Substances	Toll-Like Receptor 9 ; Ligands ; Autoantigens ; DNA, Mitochondrial
Language	English
Publishing date	2023-07-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2230457-5
ISSN	1930-739X ; 1071-7323 ; 1930-7381
ISSN (online)	1930-739X
ISSN	1071-7323 ; 1930-7381
DOI	10.1002/oby.23805
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Article ; Online: Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells.

Liu, Chinky Shiu Chen / Mandal, Tithi / Biswas, Parijat / Hoque, Md Asmaul / Bandopadhyay, Purbita / Sinha, Bishnu Prasad / Sarif, Jafar / D'Rozario, Ranit / Sinha, Deepak Kumar / Sinha, Bidisha / Ganguly, Dipyaman

eLife

2024 Volume 12

Abstract: T cells are crucial for efficient antigen-specific immune responses and thus their migration within the body, to inflamed tissues from circulating blood or to secondary lymphoid organs, plays a very critical role. T cell extravasation in inflamed tissues ...

Abstract	T cells are crucial for efficient antigen-specific immune responses and thus their migration within the body, to inflamed tissues from circulating blood or to secondary lymphoid organs, plays a very critical role. T cell extravasation in inflamed tissues depends on chemotactic cues and interaction between endothelial adhesion molecules and cellular integrins. A migrating T cell is expected to sense diverse external and membrane-intrinsic mechano-physical cues, but molecular mechanisms of such mechanosensing in cell migration are not established. We explored if the professional mechanosensor Piezo1 plays any role during integrin-dependent chemotaxis of human T cells. We found that deficiency of Piezo1 in human T cells interfered with integrin-dependent cellular motility on ICAM-1-coated surface. Piezo1 recruitment at the leading edge of moving T cells is dependent on and follows focal adhesion formation at the leading edge and local increase in membrane tension upon chemokine receptor activation. Piezo1 recruitment and activation, followed by calcium influx and calpain activation, in turn, are crucial for the integrin LFA1 (CD11a/CD18) recruitment at the leading edge of the chemotactic human T cells. Thus, we find that Piezo1 activation in response to local mechanical cues constitutes a membrane-intrinsic component of the 'outside-in' signaling in human T cells, migrating in response to chemokines, that mediates integrin recruitment to the leading edge.
MeSH term(s)	Humans ; Cell Adhesion ; Cell Movement ; Chemokines ; Chemotaxis ; Lymphocyte Function-Associated Antigen-1 ; T-Lymphocytes ; Ion Channels/metabolism
Chemical Substances	Chemokines ; Lymphocyte Function-Associated Antigen-1 ; PIEZO1 protein, human ; Ion Channels
Language	English
Publishing date	2024-02-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.91903
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Article ; Online: Self-Nucleic Acid Sensing: A Novel Crucial Pathway Involved in Obesity-Mediated Metaflammation and Metabolic Syndrome.

Ferriere, Amandine / Santa, Pauline / Garreau, Anne / Bandopadhyay, Purbita / Blanco, Patrick / Ganguly, Dipyaman / Sisirak, Vanja

Frontiers in immunology

2021 Volume 11, Page(s) 624256

Abstract: Obesity and overweight are a global health problem affecting almost one third of the world population. There are multiple complications associated with obesity including metabolic syndrome that commonly lead to development of type II diabetes and non- ... ...

Abstract	Obesity and overweight are a global health problem affecting almost one third of the world population. There are multiple complications associated with obesity including metabolic syndrome that commonly lead to development of type II diabetes and non-alcoholic fatty liver disease. The development of metabolic syndrome and severe complications associated with obesity is attributed to the chronic low-grade inflammation that occurs in metabolic tissues such as the liver and the white adipose tissue. In recent years, nucleic acids (mostly DNA), which accumulate systemically in obese individuals, were shown to aberrantly activate innate immune responses and thus to contribute to metabolic tissue inflammation. This minireview will focus on (i) the main sources and forms of nucleic acids that accumulate during obesity, (ii) the sensing pathways required for their detection, and (iii) the key cellular players involved in this process. Fully elucidating the role of nucleic acids in the induction of inflammation induced by obesity would promote the identification of new and long-awaited therapeutic approaches to limit obesity-mediated complications.
MeSH term(s)	Adipose Tissue/immunology ; Adipose Tissue/pathology ; DNA/immunology ; Diabetes Mellitus, Type 2/immunology ; Diabetes Mellitus, Type 2/pathology ; Humans ; Inflammation/immunology ; Inflammation/pathology ; Metabolic Syndrome/immunology ; Metabolic Syndrome/pathology ; Non-alcoholic Fatty Liver Disease/immunology ; Non-alcoholic Fatty Liver Disease/pathology ; Obesity/immunology ; Obesity/pathology ; Signal Transduction/immunology
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2021-01-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.624256
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Article ; Online: Development, Optimization, and In Vivo Validation of New Imidazopyridine Chemotypes as Dual TLR7/TLR9 Antagonists through Activity-Directed Sequential Incorporation of Relevant Structural Subunits.

Das, Nirmal / Bandopadhyay, Purbita / Roy, Swarnali / Sinha, Bishnu Prasad / Dastidar, Uddipta Ghosh / Rahaman, Oindrila / Pal, Sourav / Ganguly, Dipyaman / Talukdar, Arindam

Journal of medicinal chemistry

2022 Volume 65, Issue 17, Page(s) 11607–11632

Abstract: Undesirable activation of endosomal toll-like receptors TLR7 and TLR9 present in specific immune cells in response to host-derived ligands is implicated in several autoimmune diseases and other contexts of autoreactive inflammation, making them important ...

Abstract	Undesirable activation of endosomal toll-like receptors TLR7 and TLR9 present in specific immune cells in response to host-derived ligands is implicated in several autoimmune diseases and other contexts of autoreactive inflammation, making them important therapeutic targets. We report a drug development strategy identifying a new chemotype for incorporating relevant structural subunits into the basic imidazopyridine core deemed necessary for potent TLR7 and TLR9 dual antagonism. We established minimal pharmacophoric features in the core followed by hit-to-lead optimization, guided by in vitro and in vivo biological assays and ADME. A ligand-receptor binding hypothesis was proposed, and selectivity studies against TLR8 were performed. Oral absorption and efficacy of lead candidate
MeSH term(s)	Imidazoles/pharmacology ; Ligands ; Pyridines/pharmacology ; Toll-Like Receptor 7/metabolism ; Toll-Like Receptor 9
Chemical Substances	Imidazoles ; Ligands ; Pyridines ; Toll-Like Receptor 7 ; Toll-Like Receptor 9 ; imidazopyridine
Language	English
Publishing date	2022-08-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.2c00386
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Article: Association of gut microbial dysbiosis with disease severity, response to therapy and disease outcomes in Indian patients with COVID-19.

Talukdar, Daizee / Bandopadhyay, Purbita / Ray, Yogiraj / Paul, Shekhar Ranjan / Sarif, Jafar / D'Rozario, Ranit / Lahiri, Abhishake / Das, Santanu / Bhowmick, Debaleena / Chatterjee, Shilpak / Das, Bhabatosh / Ganguly, Dipyaman

Gut pathogens

2023 Volume 15, Issue 1, Page(s) 22

Abstract: Background: Severe coronavirus disease 2019 (COVID-19) is associated with systemic hyper-inflammation. An adaptive interaction between gut microbiota and host immune systems is important for intestinal homeostasis and systemic immune regulation. The ... ...

Abstract	Background: Severe coronavirus disease 2019 (COVID-19) is associated with systemic hyper-inflammation. An adaptive interaction between gut microbiota and host immune systems is important for intestinal homeostasis and systemic immune regulation. The association of gut microbial composition and functions with COVID-19 disease severity is sparse, especially in India. We analysed faecal microbial diversity and abundances in a cohort of Indian COVID-19 patients to identify key signatures in the gut microbial ecology in patients with severe COVID-19 disease as well as in response to different therapies. The composition of the gut microbiome was characterized using 16Sr RNA gene sequences of genomic DNA extracted from faecal samples of 52 COVID-19 patients. Metabolic pathways across the groups were predicted using PICRUSt2. All statistical analyses were done using Vegan in the R environment. Plasma cytokine abundance at recruitment was measured in a multiplex assay. Results: The gut microbiome composition of mild and severe patients was found to be significantly different. Immunomodulatory commensals, viz. Lachnospiraceae family members and Bifidobacteria producing butyrate and short-chain fatty acids (SCFAs), were under represented in patients with severe COVID-19, with an increased abundance of opportunistic pathogens like Eggerthella. The higher abundance of Lachnoclostridium in severe disease was reduced in response to convalescent plasma therapy. Specific microbial genera showed distinctive trends in enriched metabolic pathways, strong correlations with blood plasma cytokine levels, and associative link to disease outcomes. Conclusion: Our study indicates that, along with SARS-CoV-2, a dysbiotic gut microbial community may also play an important role in COVID-19 severity through modulation of host immune responses.
Language	English
Publishing date	2023-05-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2478277-4
ISSN	1757-4749
ISSN	1757-4749
DOI	10.1186/s13099-023-00546-z
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Article ; Online: Deficient Phagocytosis in Circulating Monocytes from Patients with COVID-19-Associated Mucormycosis.

Sinha, Bishnu Prasad / Mehta, Priyanka / Hoque, Md Asmaul / Bandopadhyay, Purbita / Nandi, Ayandip / Saha, Ipsita / Nandi Mitra, Anita / Mondal, Asish / Bhattacharjee, Boudhayan / Chamilos, Georgios / Pandey, Rajesh / Basu, Kaushik / Ganguly, Dipyaman

mBio

2023 Volume 14, Issue 3, Page(s) e0059023

Abstract: Cases of rhino-orbital mucormycosis in patients suffering from severe coronavirus disease 2019 (COVID-19) were reported in different parts of the world, especially in India. However, specific immune mechanisms that are linked to susceptibility to COVID- ... ...

Abstract	Cases of rhino-orbital mucormycosis in patients suffering from severe coronavirus disease 2019 (COVID-19) were reported in different parts of the world, especially in India. However, specific immune mechanisms that are linked to susceptibility to COVID-19-associated mucormycosis (CAM) remain largely unexplored. We aimed to explore whether the differential regulation of circulating cytokines in CAM patients had any potential pathogenic links with myeloid phagocyte function and susceptibility to mucormycosis. A small cohort of Indian patients suffering from CAM (N = 9) as well as COVID-19 patients with no evidence of mucormycosis (N = 5) were recruited in the study. Venous blood was collected from the patients as well as from healthy volunteers (N = 8). Peripheral blood mononuclear cells and plasma were isolated. Plasma samples were used to measure a panel of 48 cytokines. CD14
MeSH term(s)	Humans ; Mucormycosis ; Monocytes ; Leukocytes, Mononuclear ; COVID-19 ; Phagocytosis ; Cytokines
Chemical Substances	Cytokines
Language	English
Publishing date	2023-04-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.00590-23
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Article ; Online: Mitigating hERG Liability of Toll-Like Receptor 9 and 7 Antagonists through Structure-Based Design.

Das, Nirmal / Bhattacharya, Debomita / Bandopadhyay, Purbita / Dastidar, Uddipta Ghosh / Paul, Barnali / Rahaman, Oindrila / Hoque, Israful / Patra, Binita / Ganguly, Dipyaman / Talukdar, Arindam

ChemMedChem

2023 Volume 18, Issue 12, Page(s) e202300069

Abstract: hERG is considered to be a primary anti-target in the drug development process, as the ... ...

Abstract	hERG is considered to be a primary anti-target in the drug development process, as the K
MeSH term(s)	Toll-Like Receptor 9/metabolism ; Toll-Like Receptor 7 ; Ether-A-Go-Go Potassium Channels
Chemical Substances	Toll-Like Receptor 9 ; Toll-Like Receptor 7 ; Ether-A-Go-Go Potassium Channels
Language	English
Publishing date	2023-04-18
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2218496-X
ISSN	1860-7187 ; 1860-7179
ISSN (online)	1860-7187
ISSN	1860-7179
DOI	10.1002/cmdc.202300069
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Article ; Online: Hit-to-lead optimization of 2-aminoquinazolines as anti-microbial agents against Leishmania donovani.

European journal of medicinal chemistry

2024 Volume 269, Page(s) 116256

Abstract: Visceral leishmaniasis is a potentially fatal disease caused by infection by the intracellular protist pathogens Leishmania donovani or Leishmania infantum. Present therapies are ineffective because of high costs, variable efficacy against different ... ...

Abstract	Visceral leishmaniasis is a potentially fatal disease caused by infection by the intracellular protist pathogens Leishmania donovani or Leishmania infantum. Present therapies are ineffective because of high costs, variable efficacy against different species, the requirement for hospitalization, toxicity and drug resistance. Detailed analysis of previously published hit molecules suggested a crucial role of 'guanidine' linkage for their efficacy against L. donovani. Here we report the design of 2-aminoquinazoline heterocycle as a basic pharmacophore-bearing guanidine linkage. The introduction of various groups and functionality at different positions of the quinazoline scaffold results in enhanced antiparasitic potency with modest host cell cytotoxicity using a physiologically relevant THP-1 transformed macrophage infection model. In terms of the ADME profile, the C7 position of quinazoline was identified as a guiding tool for designing better molecules. The good ADME profile of the compounds suggests that they merit further consideration as lead compounds for treating visceral leishmaniasis.
MeSH term(s)	Humans ; Leishmania donovani ; Leishmaniasis, Visceral/drug therapy ; Antiparasitic Agents/pharmacology ; Leishmania infantum ; Quinazolines/pharmacology ; Quinazolines/therapeutic use
Chemical Substances	Antiparasitic Agents ; Quinazolines
Language	English
Publishing date	2024-02-27
Publishing country	France
Document type	Journal Article
ZDB-ID	188597-2
ISSN	1768-3254 ; 0009-4374 ; 0223-5234
ISSN (online)	1768-3254
ISSN	0009-4374 ; 0223-5234
DOI	10.1016/j.ejmech.2024.116256
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