97 results on '"Piu Saha"'
Search Results
2. Sex Dimorphic Effects of Bile Acid Metabolism in Liver Cancer in MiceSummary
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Rachel M. Golonka, Beng San Yeoh, Piu Saha, Yuan Tian, John Y.L. Chiang, Andrew D. Patterson, Andrew T. Gewirtz, Bina Joe, and Matam Vijay-Kumar
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Hepatocellular Carcinoma ,Cholestasis ,Farnesoid X Receptor ,Portosystemic Shunt ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Hepatocellular carcinoma (HCC) is a male-dominant disease, but targeted sex hormone therapies have not been successful. Bile acids are a potential liver carcinogen and are biomolecules with hormone-like effects. A few studies highlight their potential sex dimorphism in physiology and disease. We hypothesized that bile acids could be a potential molecular signature that explains sex disparity in HCC. Methods & Results: We used the farnesoid X receptor knockout (FxrKO) mouse model to study bile acid-dependent HCC. Temporal tracking of circulating bile acids determined more than 80% of FxrKO females developed spontaneous cholemia (ie, serum total bile acids ≥40 μmol/L) as early as 8 weeks old. Opposingly, FxrKO males were highly resistant to cholemia, with ∼23% incidence even when 26 weeks old. However, FxrKO males demonstrated higher levels of deoxycholate than females. Compared with males, FxrKO females had more severe cholestatic liver injury and further aberrancies in bile acid metabolism. Yet, FxrKO females expressed more detoxification transcripts and had greater renal excretion of bile acids. Intervention with CYP7A1 (rate limiting enzyme for bile acid biosynthesis) deficiency or taurine supplementation either completely or partially normalized bile acid levels and liver injury in FxrKO females. Despite higher cholemia prevalence in FxrKO females, their tumor burden was less compared with FxrKO males. An exception to this sex-dimorphic pattern was found in a subset of male and female FxrKO mice born with congenital cholemia due to portosystemic shunt, where both sexes had comparable robust HCC. Conclusions: Our study highlights bile acids as sex-dimorphic metabolites in HCC except in the case of portosystemic shunt.
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- 2024
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3. Bacterial flagellin is a dominant, stable innate immune activator in the gastrointestinal contents of mice and rats
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Matam Vijay-Kumar, Venugopal R. Bovilla, Beng San Yeoh, Rachel M. Golonka, Piu Saha, Bina Joe, and Andrew T. Gewirtz
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Gut microbiota ,LPS ,MyD88 ,toll-like Receptor-5 ,toll-like Receptor-4 ,cytokines ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
ABSTRACTIntestinal contents comprise the largest repository of immunogenic ligands of microbial origin. We undertook this study to assess the predominant microbe-associated molecular patterns (MAMPs) present therein and the receptors) that mediate the innate immune responses to them. Here, we demonstrated that intestinal contents from conventional, but not germ-free, mice and rats triggered robust innate immune responses in vitro and in vivo. Such immune responses were abrogated in the absence of either myeloid differentiation factor 88 (MyD88) or Toll-like receptor (TLR) 5, but not TLR4, suggesting that the stimuli was flagellin (i.e., protein subunit of flagella that drives bacterial motility). Accordingly, pre-treating intestinal extracts with proteinase, thereby degrading flagellin, was sufficient to block their ability to activate innate immune responses. Taken together, this work serves to underscore flagellin as a major, heat-stable and bioactive MAMP in the intestinal content that confers this milieu strong potential to trigger innate immune responses.
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- 2023
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4. Assessment of the performance of GIS-based analytical hierarchical process (AHP) approach for flood modelling in Uttar Dinajpur district of West Bengal, India
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Rajib Mitra, Piu Saha, and Jayanta Das
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Flood ,multi-criteria decision analysis (MCDA) ,ROC-AUC ,sensitivity analyses ,Uttar Dinajpur district ,Environmental technology. Sanitary engineering ,TD1-1066 ,Environmental sciences ,GE1-350 ,Risk in industry. Risk management ,HD61 - Abstract
Floods have received global significance in contemporary times due to their destructive behavior, which may wreak tremendous ruin on infrastructure and civilization. The present research employed an integration of the Geographic information system (GIS) and Analytical Hierarchy Process (AHP) method for identifying the flood susceptibility zonation (FSZ), flood vulnerability zonation (FVZ), and flood risk zonation (FRZ) of the humid subtropical Uttar Dinajpur district in India. The study combined a large number of thematic layers (N = 12 for FSZ and N = 9 for FVZ) to achieve reliable accuracy and included the multicollinearity analysis of these variables to overcome the issues related to highly correlated variables. According to the findings, 27.04, 15.62, and 4.59% of the area were classified as medium, high, and very high FRZ, respectively. The ROC-AUC, MAE, MSE, and RMSE of the model exhibited a good prediction accuracy of 0.73, 0.15, 0.16, and 0.21, respectively. The performance of the AHP model has been evaluated using sensitivity analyses. It also highly recommends that persistent improvement in this subject, such as sensitivity studies on modifying criteria thresholds, changing the relative significance of criteria, and changing the desired matrix, will permit GIS and MCDA to be progressively adapted to real hazard-management issues.
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- 2022
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5. Combating hypertension beyond genome-wide association studies: Microbiome and artificial intelligence as opportunities for precision medicine
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Sachin Aryal, Ishan Manandhar, Xue Mei, Beng S. Yeoh, Ramakumar Tummala, Piu Saha, Islam Osman, Jasenka Zubcevic, David J. Durgan, Matam Vijay-Kumar, and Bina Joe
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Machine learning ,high blood pressure ,gut microbiota ,genome-based risk scores ,personalized medicine ,Internal medicine ,RC31-1245 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The single largest contributor to human mortality is cardiovascular disease, the top risk factor for which is hypertension (HTN). The last two decades have placed much emphasis on the identification of genetic factors contributing to HTN. As a result, over 1,500 genetic alleles have been associated with human HTN. Mapping studies using genetic models of HTN have yielded hundreds of blood pressure (BP) loci but their individual effects on BP are minor, which limits opportunities to target them in the clinic. The value of collecting genome-wide association data is evident in ongoing research, which is beginning to utilize these data at individual-level genetic disparities combined with artificial intelligence (AI) strategies to develop a polygenic risk score (PRS) for the prediction of HTN. However, PRS alone may or may not be sufficient to account for the incidence and progression of HTN because genetics is responsible for
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- 2023
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6. Crosstalk between Gut Microbiota and Host Immunity: Impact on Inflammation and Immunotherapy
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Connor Campbell, Mrunmayee R. Kandalgaonkar, Rachel M. Golonka, Beng San Yeoh, Matam Vijay-Kumar, and Piu Saha
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gut microbiota dysbiosis ,innate immune system ,adaptive immune system ,infection ,cancer ,inflammatory bowel diseases ,Biology (General) ,QH301-705.5 - Abstract
Gut microbes and their metabolites are actively involved in the development and regulation of host immunity, which can influence disease susceptibility. Herein, we review the most recent research advancements in the gut microbiota–immune axis. We discuss in detail how the gut microbiota is a tipping point for neonatal immune development as indicated by newly uncovered phenomenon, such as maternal imprinting, in utero intestinal metabolome, and weaning reaction. We describe how the gut microbiota shapes both innate and adaptive immunity with emphasis on the metabolites short-chain fatty acids and secondary bile acids. We also comprehensively delineate how disruption in the microbiota–immune axis results in immune-mediated diseases, such as gastrointestinal infections, inflammatory bowel diseases, cardiometabolic disorders (e.g., cardiovascular diseases, diabetes, and hypertension), autoimmunity (e.g., rheumatoid arthritis), hypersensitivity (e.g., asthma and allergies), psychological disorders (e.g., anxiety), and cancer (e.g., colorectal and hepatic). We further encompass the role of fecal microbiota transplantation, probiotics, prebiotics, and dietary polyphenols in reshaping the gut microbiota and their therapeutic potential. Continuing, we examine how the gut microbiota modulates immune therapies, including immune checkpoint inhibitors, JAK inhibitors, and anti-TNF therapies. We lastly mention the current challenges in metagenomics, germ-free models, and microbiota recapitulation to a achieve fundamental understanding for how gut microbiota regulates immunity. Altogether, this review proposes improving immunotherapy efficacy from the perspective of microbiome-targeted interventions.
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- 2023
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7. Enterobactin induces the chemokine, interleukin-8, from intestinal epithelia by chelating intracellular iron
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Piu Saha, Beng San Yeoh, Xia Xiao, Rachel M. Golonka, Ahmed A. Abokor, Camilla F. Wenceslau, Yatrik M. Shah, Bina Joe, and Matam Vijay-Kumar
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siderophores ,enterochelin ,il-8 ,labile iron pool ,lipocalin 2 ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Iron is an indispensable nutrient for both mammals and microbes. Bacteria synthesize siderophores to sequester host iron, whereas lipocalin 2 (Lcn2) is the host defense protein that prevent this iron thievery. Enterobactin (Ent) is a catecholate-type siderophore that has one of the strongest known affinities for iron. Intestinal epithelial cells (IECs) are adjacent to large microbial population and are in contact with microbial products, including Ent. We undertook this study to investigate whether a single stimulus of Ent could affect IEC functions. Using three human IEC cell-lines with differential basal levels of Lcn2 (i.e. HT29
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- 2020
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8. Distinct iron homeostasis in C57BL/6 and Balb/c mouse strains
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Piu Saha, Xia Xiao, Yaqi Li, Rachel M. Golonka, Ahmed A. Abokor, Beng San Yeoh, and Matam Vijay‐Kumar
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ferroportin ,hepcidin ,hypoferremia of inflammation ,innate immunity ,labile iron pool ,Physiology ,QP1-981 - Abstract
Abstract C57BL/6 (BL6) and Balb/c mice exhibit prototypical Th1‐ and Th2‐dominant immune predispositions, respectively. Iron is a proinflammatory metal ion; however, limited information is documented on the differences in iron homeostasis between BL6 and Balb/c strains. The objective of this study was to investigate the extent to which strain‐level differences in these mice dictates the regulation of iron homeostasis during physiologic and inflammatory conditions. At basal levels, Balb/c mice displayed significantly higher levels of iron in systemic circulation and tissue compared to BL6 mice. Moreover, Balb/c mice had greater iron absorption as indicated by higher gene expressions of duodenal DcytB, DMT1, Fpn, SFT, and Heph. Similarly, hepatic Tf, TfR1, TfR2, and DMT1 expressions were augmented in Balb/c mice. Interestingly, there was no change in hepatic Hamp expression between the two strains, suggesting that the disparity in their maintenance of iron is independent of hepcidin. Additionally, the basal levels of intracellular labile iron pool in Balb/c intestinal epithelial cells, and bone marrow‐derived macrophages and neutrophils, were higher compared to BL6 mice. When mice were challenged with lipopolysaccharide, the acute inflammatory response in BL6 mice was more pronounced than in Balb/c mice, as indicated by the more rapid development of hypoferremia and upregulation of serum IL‐6 and TNF‐α levels in BL6 mice. In conclusion, this study underscores that iron homeostasis is distinct between BL6 and Balb/c strains under both physiologic and inflammatory conditions.
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- 2020
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9. Functional MAIT Cells Are Associated With Reduced Simian–Human Immunodeficiency Virus Infection
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Amudhan Murugesan, Chris Ibegbu, Tiffany M. Styles, Andrew T. Jones, Uma Shanmugasundaram, Pradeep B. J. Reddy, Sadia J. Rahman, Piu Saha, Matam Vijay-Kumar, Esaki Muthu Shankar, Rama Rao Amara, and Vijayakumar Velu
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MAIT cells ,HIV/SIV infection ,CD8 T cells ,rhesus macaques ,innate like T cells ,microbial metabolites ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Mucosa-associated invariant T (MAIT) cells are recently characterized as a novel subset of innate-like T cells that recognize microbial metabolites as presented by the MHC-1b-related protein MR1. The significance of MAIT cells in anti-bacterial defense is well-understood but not clear in viral infections such as SIV/HIV infection. Here we studied the phenotype, distribution, and function of MAIT cells and their association with plasma viral levels during chronic SHIV infection in rhesus macaques (RM). Two groups of healthy and chronic SHIV-infected macaques were characterized for MAIT cells in blood and mucosal tissues. Similar to human, we found a significant fraction of macaque T cells co-expressing MAIT cell markers CD161 and TCRVα-7.2 that correlated directly with macaque MR1 tetramer. These cells displayed memory phenotype and expressed high levels of IL-18R, CCR6, CD28, and CD95. During chronic infection, the frequency of MAIT cells are enriched in the blood but unaltered in the rectum; both blood and rectal MAIT cells displayed higher proliferative and cytotoxic phenotype post-SHIV infection. The frequency of MAIT cells in blood and rectum correlated inversely with plasma viral RNA levels and correlated directly with total CD4 T cells. MAIT cells respond to microbial products during chronic SHIV infection and correlated positively with serum immunoreactivity to flagellin levels. Tissue distribution analysis of MAIT cells during chronic infection showed significant enrichment in the non-lymphoid tissues (lung, rectum, and liver) compared to lymphoid tissues (spleen and LN), with higher levels of tissue-resident markers CD69 and CD103. Exogenous in vitro cytokine treatments during chronic SHIV infection revealed that IL-7 is important for the proliferation of MAIT cells, but IL-12 and IL-18 are important for their cytolytic function. Overall our results demonstrated that MAIT cells are enriched in blood but unaltered in the rectum during chronic SHIV infection, which displayed proliferative and functional phenotype that inversely correlated with SHIV plasma viral RNA levels. Treatment such as combined cytokine treatments could be beneficial for enhancing functional MAIT cells during chronic HIV infection in vivo.
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- 2020
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10. Immunoglobulin A, an Active Liaison for Host-Microbiota Homeostasis
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Ahmed A. Abokor, Grant H. McDaniel, Rachel M. Golonka, Connor Campbell, Sreya Brahmandam, Beng San Yeoh, Bina Joe, Matam Vijay-Kumar, and Piu Saha
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secretory IgA ,gut homeostasis ,IgA deficiency ,polymeric immunoglobulin receptor (pIgR) ,mucosal immunology ,B cells ,Biology (General) ,QH301-705.5 - Abstract
Mucosal surfaces in the gastrointestinal tract are continually exposed to native, commensal antigens and susceptible to foreign, infectious antigens. Immunoglobulin A (IgA) provides dual humoral responses that create a symbiotic environment for the resident gut microbiota and prevent the invasion of enteric pathogens. This review features recent immunological and microbial studies that elucidate the underlying IgA and microbiota-dependent mechanisms for mutualism at physiological conditions. IgA derailment and concurrent microbiota instability in pathological diseases are also discussed in detail. Highlights of this review underscore that the source of IgA and its structural form can dictate microbiota reactivity to sustain a diverse niche where both host and bacteria benefit. Other important studies emphasize IgA insufficiency can result in the bloom of opportunistic pathogens that encroach the intestinal epithelia and disseminate into circulation. The continual growth of knowledge in these subjects can lead to the development of therapeutics targeting IgA and/or the microbiota to treat life threatening diseases.
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- 2021
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11. Data on importance of hematopoietic cell derived Lipocalin 2 against gut inflammation
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Piu Saha, Vishal Singh, Xia Xiao, Beng San Yeoh, and Matam Vijay-Kumar
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Computer applications to medicine. Medical informatics ,R858-859.7 ,Science (General) ,Q1-390 - Abstract
The data herein is related to the research article entitled “Microbiota-inducible innate immune siderophore binding protein Lipocalin 2 is critical for intestinal homeostasis” (Singh et al., 2016) [1]. In the present article, we monitored dextran sodium sulfate (DSS)-induced colitis development upon Lipocalin 2 (Lcn2) neutralization, and examined the survival of Lcn2 deficient (Lcn2KO) mice and their WT littermates upon DSS challenge. To dissect the relative contribution of immune and non-immune cells-derived Lcn2 in mediating protection against gut inflammation, we generated respective bone marrow chimera and evaluated their susceptibility to IL-10 receptor neutralization-induced chronic colitis.Neutralization of Lcn2 in WT mice resulted in exacerbated DSS-induced colitis. Notably, mice lacking Lcn2 exhibited 100% mortality whereas only 20% mortality was observed in WT mice upon DSS challenge. Further, data from bone marrow chimera showed that immune cell-derived Lcn2 is the major contributor in conferring protection against colitis. Keywords: Siderocalin, Gut microbiota, Inflammatory bowel disease, Bone marrow chimeras, Colitis
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- 2016
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12. Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension
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Saroj Chakraborty, Sarah Galla, Xi Cheng, Ji-Youn Yeo, Blair Mell, Vishal Singh, BengSan Yeoh, Piu Saha, Anna V. Mathew, Matam Vijay-Kumar, and Bina Joe
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Biology (General) ,QH301-705.5 - Abstract
Summary: Dietary salt reduction and exercise are lifestyle modifications for salt-sensitive hypertensives. While exercise has prominent metabolic effects, salt has an adverse effect on metabolic syndrome, of which hypertension is a hallmark. We hypothesized that dietary salt impacts metabolism in a salt-sensitive model of hypertension. An untargeted metabolomic approach demonstrates lower circulating levels of the ketone body, beta-hydroxybutyrate (βOHB), in high salt-fed hypertensive rats. Despite the high salt intake, specific rescue of βOHB levels by nutritional supplementation of its precursor, 1,3-butanediol, attenuates hypertension and protects kidney function. This beneficial effect of βOHB was likely independent of gut-microbiotal and Th17-mediated effects of salt and instead facilitated by βOHB inhibiting the renal Nlrp3 inflammasome. The juxtaposed effects of dietary salt and exercise on salt-sensitive hypertension, which decrease and increase βOHB respectively, indicate that nutritional supplementation of a precursor of βOHB provides a similar benefit to salt-sensitive hypertension as exercise. : Chakraborty et al. report a link between dietary salt, a ketone, and experimental hypertension. Intake of a high salt diet lowers the ketone body beta-hydroxybutyrate (βOHB), produced by the liver, which functions to prevent Nlrp3-mediated kidney inflammation. Rescuing βOHB by nutritional supplementation of its precursor attenuates hypertension. Keywords: hypertension, metabolomics, ketone body, salt, blood pressure, β-hydroxybutyrate, inflammation, Nlrp3, inflammasome, kidney
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- 2018
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13. Microbiota-Inducible Innate Immune Siderophore Binding Protein Lipocalin 2 Is Critical for Intestinal HomeostasisSummary
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Vishal Singh, Beng San Yeoh, Benoit Chassaing, Benyue Zhang, Piu Saha, Xia Xiao, Deepika Awasthi, Rangaiah Shashidharamurthy, Madhu Dikshit, Andrew Gewirtz, and Matam Vijay-Kumar
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background & Aims: Lipocalin 2 (Lcn2) is a multifunctional innate immune protein whose expression closely correlates with the extent of intestinal inflammation. However, whether Lcn2 plays a role in the pathogenesis of gut inflammation is unknown. Herein, we investigated the extent to which Lcn2 regulates inflammation and gut bacterial dysbiosis in mouse models of IBD. Methods: Lcn2 expression was monitored in murine colitis models and upon microbiota ablation/restoration. Wild-type (WT) and Lcn2 knockout (Lcn2KO) mice were analyzed for gut bacterial load, composition by 16S ribosomal RNA gene pyrosequencing, and their colitogenic potential by co-housing with interleukin (Il)10KO mice. Acute (dextran sodium sulfate) and chronic (IL10R neutralization and T-cell adoptive transfer) colitis were induced in WT and Lcn2KO mice with or without antibiotics. Results: Lcn2 expression was dramatically induced on inflammation and was dependent on the presence of a gut microbiota and MyD88 signaling. Use of bone marrowâchimeric mice showed that nonimmune cells are the major contributors of circulating Lcn2. Lcn2KO mice showed increased levels of entA-expressing gut bacteria burden, and, moreover, a broadly distinct bacterial community relative to WT littermates. Lcn2KO mice developed highly colitogenic T cells and showed exacerbated colitis on exposure to DSS or neutralization of IL10. Such exacerbated colitis could be prevented by antibiotic treatment. Moreover, exposure to the microbiota of Lcn2KO mice, via cohousing, resulted in severe colitis in Il10KO mice. Conclusions: Lcn2 is a bacterially induced, MyD88-dependent protein that plays an important role in gut homeostasis and a pivotal role on challenge. Hence, therapeutic manipulation of Lcn2 levels may provide a strategy to help manage diseases driven by alteration of the gut microbiota. Keywords: Gut Microbiota, Innate Immunity, Germ-Free Mice, MyD88, Colitis, NGAL, Siderocalin, Neutrophils, IBD
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- 2016
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14. Gut Microbiota Conversion of Dietary Ellagic Acid into Bioactive Phytoceutical Urolithin A Inhibits Heme Peroxidases.
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Piu Saha, Beng San Yeoh, Rajbir Singh, Bhargavi Chandrasekar, Praveen Kumar Vemula, Bodduluri Haribabu, Matam Vijay-Kumar, and Venkatakrishna R Jala
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Medicine ,Science - Abstract
Numerous studies signify that diets rich in phytochemicals offer many beneficial functions specifically during pathologic conditions, yet their effects are often not uniform due to inter-individual variation. The host indigenous gut microbiota and their modifications of dietary phytochemicals have emerged as factors that greatly influence the efficacy of phytoceutical-based intervention. Here, we investigated the biological activities of one such active microbial metabolite, Urolithin A (UA or 3,8-dihydroxybenzo[c]chromen-6-one), which is derived from the ellagic acid (EA). Our study demonstrates that UA potently inhibits heme peroxidases i.e. myeloperoxidase (MPO) and lactoperoxidase (LPO) when compared to the parent compound EA. In addition, chrome azurol S (CAS) assay suggests that EA, but not UA, is capable of binding to Fe3+, due to its catechol-like structure, although its modest heme peroxidase inhibitory activity is abrogated upon Fe3+-binding. Interestingly, UA-mediated MPO and LPO inhibition can be prevented by innate immune protein human NGAL or its murine ortholog lipocalin 2 (Lcn2), implying the complex nature of host innate immunity-microbiota interactions. Spectral analysis indicates that UA inhibits heme peroxidase-catalyzed reaction by reverting the peroxidase back to its inactive native state. In support of these in vitro results, UA significantly reduced phorbol myristate acetate (PMA)-induced superoxide generation in neutrophils, however, EA failed to block the superoxide generation. Treatment with UA significantly reduced PMA-induced mouse ear edema and MPO activity compared to EA treated mice. Collectively, our results demonstrate that microbiota-mediated conversion of EA to UA is advantageous to both host and microbiota i.e. UA-mediated inhibition of pro-oxidant enzymes reduce tissue inflammation, mitigate non-specific killing of gut bacteria, and abrogate iron-binding property of EA, thus providing a competitive edge to the microbiota in acquiring limiting nutrient iron and thrive in the gut.
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- 2016
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15. Combating Hypertension Beyond GWAS: Microbiome and Artificial Intelligence as Opportunities for Precision Medicine
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Sachin Aryal, Ishan Manandhar, Xue Mei, Beng San Yeoh, Ramakumar Tummala, Piu Saha, Islam Osman, Jasenka Zubcevic, David J. Durgan, Matam Vijay-Kumar, and Bina Joe
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- 2023
16. Conjugated bile acids are nutritionally re-programmable antihypertensive metabolites
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Saroj Chakraborty, Anju Lulla, Xi Cheng, Ji-Youn Yeo, Juthika Mandal, Tao Yang, Xue Mei, Piu Saha, Rachel M. Golonka, Beng San Yeoh, Blair Mell, Wei Jia, Vasanta Putluri, Danthasinghe Waduge Badrajee Piyarathna, Nagireddy Putluri, Arun Sreekumar, Katie Meyer, Matam Vijay-Kumar, and Bina Joe
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Physiology ,Internal Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
17. Selective IgA Deficiency in Spontaneously Hypertensive Rats With Gut Dysbiosis
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Piu Saha, Blair Mell, Rachel M. Golonka, Venugopal R. Bovilla, Ahmed A. Abokor, Xue Mei, Beng San Yeoh, Peter A. Doris, Andrew T. Gewirtz, Bina Joe, and Matam Vijay-Kumar
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Immunoglobulin M ,Immunoglobulin G ,Rats, Inbred SHR ,Hypertension ,Internal Medicine ,IgA Deficiency ,Animals ,Dysbiosis ,Blood Pressure ,Rats, Inbred WKY ,Immunoglobulin A ,Rats - Abstract
Background:The spontaneously hypertensive rat (SHR) is extensively used to study hypertension. Gut microbiota dysbiosis is a notable feature in SHR for reasons unknown. Immunoglobulin A (IgA) is a major host factor required for gut microbiota homeostasis. We hypothesized that inadequate IgA contributes to gut microbiota dysbiosis in SHR.methods:IgA was measured in feces, cecum, serum, liver, gut-associated lymphoid tissue, and milk from SHR and Wistar Kyoto rats. IgA regulatory factors like IgM, IgG, andpIgR(polymeric immunoglobulin receptor) were analyzed. IgA and IgG antibodies and blood pressure (BP) were measured before and after administrating a bacterial antigen (ie, flagellin).Results:Compared with Wistar Kyoto rats, SHR displayed remarkably near-deficient IgA levels accompanied by compensatory increases in serum IgM and IgG and gut-liverpIgRexpression. Inadequate milk IgA in SHR emphasized this immune defect stemmed from the neonatal stage. Reduced IgA+B cells in circulation and Peyer patches indicated a possible reason for the lower IgA in SHR. Noteworthy, a genetic insufficiency was unlikely because administering flagellin to SHR induced anti-flagellin IgA antibodies. This immune response surprisingly accelerated hypertension development in SHR, suggesting IgA quiescence may help maintain lower BP.Conclusions:This study is the first to reveal IgA deficiency in SHR as one host factor associated with gut microbiota dysbiosis and invigorates future research to determine the pathophysiological role of IgA in hypertension.
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- 2023
18. Loss of toll-like receptor 5 potentiates spontaneous hepatocarcinogenesis in farnesoid X receptor–deficient mice
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Rachel M. Golonka, Beng San Yeoh, Piu Saha, Amira Gohara, Ramakumar Tummala, Stanislaw Stepkowski, Amit K. Tiwari, Bina Joe, Frank J. Gonzalez, Andrew T. Gewirtz, and Matam Vijay-Kumar
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Hepatology - Published
- 2023
19. Investigation of spatio-temporal variability of meteorological drought in the Luni River Basin, Rajasthan, India
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Jiarul Alam, Piu Saha, Rajib Mitra, and Jayanta Das
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General Earth and Planetary Sciences ,General Environmental Science - Published
- 2023
20. A review on municipal solid wastes and their associated problems and solutions (waste-to-energy recovery and nano-treatment) with special reference to India
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Piu Saha and Sumi Handique
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- 2023
21. List of contributors
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Abdul-Salam Jahanfo Abdulai, Sangita Agarwal, Nufile Uddin Ahmed, Waqas Ali, Ingrid R.F.S. Alves, Charu Arora, Michael Osei Asibey, Taniya Banerjee, Isabelli D. Bassin, João Paulo Bassin, Shelly Bhardwaj, Dipti Bharti, Muhammad Bilal, Amilton Barbosa Botelho Júnior, Syed Mohsin Bukhari, Francine Duarte Castro, Manisha Chandel, Nalini Singh Chauhan, Moharana Choudhury, Ankita Chowdhury, Laura Cutaia, Peter Dabnichki, Soumendra Darbar, Sujit Das, Tanushri Das, Shailja Dhiman, Ananya Dutta, Denise Espinosa, Luíza Santana Franca, Neanderson Galvão, Imania Ghaffar, Tania Ghatak, Arti Goel, Juhi Gupta, Marlia M. Hanafiah, Sumi Handique, Md. Sanowar Hossain, Ali Hussain, Haikal Ismail, Arti Jain, Arshad Javid, Benjamin Dosu Jnr, Jaskiran Kaur, Shilpi Khurana, Deeksha Krishna, Amit Kumar, Roopa Kumari, Tanu Kumari, Smitha M.S., Sophayo Mahongnao, Himadrija Majumder, Priti Malhotra, Ana Paula Martinho, Mahadi Hasan Masud, Bisma Meer, Kushif Meer, Tahir Mehmood, Syed Ghulam Mohayud Din Hashmi, Monjur Mourshed, Fareeha Nadeem, Ammu P. Nair, Sarita Nanda, Asha Patel, Deepak Pathania, Abhay Punia, Sarmad Ahmad Qamar, Akhilesh Singh Raghubanshi, Trishna Rajbongshi, Sanchayita Rajkhowa, Anita Rani, H.K. Sachan, Piu Saha, Srimoyee Saha, null Sangeeta, Abhijit Sarkar, Jyotirmoy Sarma, Ajay Sharma, Nilakshi Dhara Sharma, Pooja Sharma, Anand Narain Singh, Darshan Singh, Rahul Singh, Ravindra Pratap Singh, Siril Singh, Sanju Soni, Sahana Sultana, Jorge Tenório, Manita Thakur, Prosper Tornyeviadzi, Mentore Vaccari, Ajit Varma, Kailas L. Wasewar, Bárbara Gomes Xavier, Carlos Xavier, Elisa Silvana Xavier, and Rajni Yadav
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- 2023
22. Abstract P109: A Novel Murine Model Of Diet-induced Cholemia For Studies On The Gut-liver-kidney Axis In Blood Pressure Regulation
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Beng San Yeoh, Piu Saha, Rachel M Golonka, Ahmed A Abokor, Bina Joe, and Matam Vijay-Kumar
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Internal Medicine - Abstract
Bile acids (BA) are classically viewed as emulsifiers produced by the liver for aiding the absorption of fats in the gut. Accumulating evidence now recognizes BA as vasoactive agents capable of lowering blood pressure (BP). However, it remains unclear whether the ensuing hypotension can be associated with end-organ damage. To delineate the pathogenic role of BA in the gut-liver-kidney axis, we leveraged our prior finding that a subset of C57BL/6 mice developed cholemia ( i.e. , high circulating BA) when fed a diet supplemented with 7.5% inulin. Briefly, we challenged 4-week-old male mice (n=50) with the inulin diet for one week and identified the subset that developed cholemia (B6 BA ; n=6). Non-cholemic mice (B6; n=6) were maintained as control. Assessment on BP at 6 months of inulin feeding indicated that B6 BA mice (systolic BP: 107.6 ± 2.2 mmHg; diastolic BP: 78.6 ± 3.1 mmHg) are hypotensive relative to non-cholemic B6 mice (systolic BP: 139.8 ± 5.6 mmHg; diastolic BP: 109.0 ± 3.8 mmHg), which was accompanied by polydipsia (7.0 ± 0.4 ml/day in B6 BA vs 4.3 ± 0.2 ml/day water intake in B6), polyuria (2.5 ± 0.1 ml/day in B6 BA vs 1.2 ± 0.1 ml/day urine output in B6), and elevated urinary BA (28.5 ± 1.7 μM in B6 BA vs 3.3 ± 0.6 μM in B6) in B6 BA mice. B6 BA mice also excreted more urinary creatinine (50.4 ± 3.4 mg/dl in B6 BA vs 25.6 ± 1.3 mg/dl in B6), sodium (271.8 ± 20.1 μmol/day in B6 BA vs 103.0 ± 11.0 μmol/day in B6) and potassium (349.2 ± 16.7 μmol/day in B6 BA vs 128.7 ± 7.7 μmol/day in B6), which could be, in part, explained by their higher glomerular filtration rate (1209.0 ± 121.0 in B6 BA vs 681.2 ± 148.7 μl/min/100 g body weight in B6). Of note, B6 BA mice displayed renomegaly, interstitial nephritis, and bile casts in urine, as well as elevated renal transcripts (>2-fold increase relative to B6) for lipocalin 2, kidney injury molecule-1, tumor necrosis factor alpha, collagen type I α1 and endothelin-1. Taken together, these findings demonstrate that our mouse model of diet-induced cholemia presents with low BP and renal pathology. We envision that this model has notable advantages ( e.g. , ease in inducing cholemia, no early morbidity and tractable for long-term study), in lieu of the conventional bile duct ligation approach, for studying how BA regulate BP.
- Published
- 2022
23. Abstract P077: Targeting Neutrophilia Is A Therapeutic Strategy To Regulate Blood Pressure
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Piu Saha, Blair Mell, Xue Mei, Rachel Golonka, Saroj Chakraborty, Beng San Yeoh, Bina Joe, and Matam Vijay-Kumar
- Subjects
Internal Medicine - Abstract
Neutrophils are important innate immune cells that are relatively understudied for their contributions to blood pressure (BP) regulation. As neutrophilia is a clinical marker for various pathologies, we hypothesized that neutrophilia is also a feature of hypertension and curtailing neutrophilia is beneficial for lowering BP. Peripheral neutrophil levels were quantitated in Dahl salt-sensitive (S) and Dahl salt-resistant (R) rats consuming either a low salt (0.3% NaCl) or high salt (2% NaCl) diet. Compared to R rats, S rats on a low-salt diet already exhibited neutrophilia (% neutrophils, 33.51±1.6 vs. 39.74±1.2, pi.e., generation of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs, web-like structures of expelled neutrophil DNA). Peripheral neutrophils stimulated with either PMA or LPS showed a ~ 3-fold induction of ROS and NETs, respectively, in S rats compared to R rats on a low-salt diet. Introducing a high-salt diet increased ROS and NETs (~2-fold), the extent of elevation being higher in S rats. Impressively, treatment of S rats on a high-salt diet with 1,3-butandiol [(β - hydroxybutyrate (βOHB, a ketone body) precursor] in the drinking water (20% v/v, 4 weeks) significantly lowered neutrophilia (vehicle: 1.74±0.5 vs βOHB: 0.73±0.3 x 10 9 cells/l, p9 cells/l), albeit to a lesser degree than S rats. Importantly, βOHB administration to S and R rats also reduced NETs and ROS (~2-fold), predominantly in S rats. Collectively, our data are the first to demonstrate that an exaggerated innate immune response via neutrophilia is pathological in hypertension, whereby curbing the neutrophilic response ( e.g., βOHB) could present therapeutic potential in lowering BP.
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- 2022
24. Spatio-temporal characterization of rainfall in Bangladesh: an innovative trend and discrete wavelet transformation approaches
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Tapash Mandal, Jayanta Das, Piu Saha, and A. T. M. Sakiur Rahman
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Atmospheric Science ,Irrigation ,010504 meteorology & atmospheric sciences ,Flood myth ,0207 environmental engineering ,02 engineering and technology ,Seasonality ,Monsoon ,medicine.disease ,01 natural sciences ,Water resources ,Trend analysis ,Climatology ,Dry season ,medicine ,Environmental science ,Precipitation ,020701 environmental engineering ,0105 earth and related environmental sciences - Abstract
The analysis of detailed characteristics of rainfall is of utmost importance for understanding water resources, irrigation, and agriculture. This study investigated detailed characteristics of rainfall of Bangladesh from 1966 to 2019. Rainfall features like the precipitation concentration index (PCI) and seasonality index (SI) were estimated to characterize spatial patterns of rainfall regimes, and innovative trend analysis (ITA) and percent bias (PBIAS) were used to detect the trend, and its reliability was tested by using the Mann–Kendall (MK) or modified Mann–Kendall (mMK) test. The magnitude of changes was computed by using Sen’s slope estimator (Q), and discrete wavelet transform (DWT) was employed to find out the dominant periodicity of the trend of annual series. SI and PCI revealed that rainfall is mainly seasonal and markedly with the long dry season, and the distribution of rainfall is irregular for the major portion of Bangladesh. The result of ITA and PBIAS showed a similar trend for all the stations and time scales. ITA showed that 23 stations experienced significant (α =
- Published
- 2021
25. Microbiota Introduced to Germ-Free Rats Restores Vascular Contractility and Blood Pressure
- Author
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Xi Cheng, Cameron G. McCarthy, Saroj Chakraborty, Tao Yang, Matam Vijay-Kumar, Jiyoun Yeo, Camilla F Wenceslau, Jonnelle M Edwards, Nicole R. Bearss, Piu Saha, Bina Joe, Rachel M. Golonka, Beng San Yeoh, Blair Mell, and Janara Furtado
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Hemodynamics ,Blood Pressure ,030204 cardiovascular system & hematology ,Gut flora ,Article ,Polymerization ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Germ-Free Life ,Actin ,Cell Proliferation ,biology ,Microbiota ,Cofilin ,biology.organism_classification ,Gastrointestinal Microbiome ,Mesenteric Arteries ,Specific Pathogen-Free Organisms ,Actin Cytoskeleton ,030104 developmental biology ,Endocrinology ,Blood pressure ,Phosphorylation ,Hypotension ,medicine.symptom ,Vasoconstriction ,Homeostasis - Abstract
Commensal gut microbiota are strongly correlated with host hemodynamic homeostasis, but only broadly associated with cardiovascular health. This includes a general correspondence of quantitative and qualitative shifts in intestinal microbial communities found in hypertensive rat models and human patients. However, the mechanisms by which gut microbes contribute to the function of organs important for blood pressure control remain unanswered. To examine the direct effects of microbiota on blood pressure, we conventionalized germ-free (GF) rats with specific pathogen free rats for a short-term period of 10 days, which served as a model system to observe the dynamic responses when reconstituting the holobiome. The absence of microbiota in GF rats resulted with relative hypotension compared to their conventionalized counterparts, suggesting an obligatory role of microbiota in blood pressure homeostasis. Hypotension observed in GF rats was accompanied by a marked reduction in vascular contractility. Both blood pressure and vascular contractility were restored by the introduction of microbiota to GF rats, indicating that microbiota could be impacting blood pressure through a vascular-dependent mechanism. This is further supported by the decrease in actin polymerization in arteries from GF rats. Improved vascular contractility in conventionalized GF rats, as indicated through stabilized actin filaments, was associated with an increase in cofilin phosphorylation. These data indicate that the vascular system senses the presence (or lack of) microbiota to maintain vascular tone via actin polymerization. Taken together, these results constitute a fundamental discovery of the essential nature of microbiota in blood pressure regulation.
- Published
- 2020
26. Exploring driving forces of large-scale unsustainable groundwater development for irrigation in lower Ganga River basin in India
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Jayanta Das, Tapash Mandal, Piu Saha, and A. T. M. Sakiur Rahman
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Driving factors ,Economics and Econometrics ,geography ,Irrigation ,geography.geographical_feature_category ,Geography, Planning and Development ,0211 other engineering and technologies ,Drainage basin ,02 engineering and technology ,Groundwater recharge ,010501 environmental sciences ,Management, Monitoring, Policy and Law ,Monsoon ,Resource depletion ,01 natural sciences ,Water resources ,Environmental science ,021108 energy ,Water resource management ,Groundwater ,0105 earth and related environmental sciences - Abstract
Groundwater is the replenishable and dynamic resources on the earth. Understanding the sustainability of water management is, therefore, the crucial factor in faring about agriculture, economy and environmental conditions. This study investigated the sustainability of large-scale groundwater-based irrigation by identifying the trend in groundwater depth (GWD) and explored the driving factors to characterize the identified trends in the lower Ganga River basin (LGRB) in India with an area of 195,601 km2. Trends were identified in the in situ observation groundwater data (total wells = 527) by applying innovative trend analysis (ITA), Mann–Kendall (MK) test or modified MK (mMK) and Sen’s slope estimator. The obtained results of all the methods confirmed that GWD in most of the studied wells had an increasing tendency in LGRB during 1996–2017. ITA showed that almost 85.39%, 62.23%, 85.39% and 57.12% wells for pre-monsoon, monsoon, post-monsoon and winter seasons, respectively, showed increasing trends. The rapidly increasing trend (slope: 5.22–136.33 cm/year) in monsoon season indicates shallow groundwater resource depletion, and groundwater abstraction exceeds the groundwater recharge. Findings also revealed that shallow pumps would not be functioning in the future for large-scale irrigation since shallow water is becoming scarce due to increasing water depth. In spite of irrigated areas continued almost the same (1997–2014), decreasing rainfall along with unplanned development of water resources is primarily identified as the main driving force for groundwater depletion at a large scale. Planned water management is urgent for ensuring sustainable irrigation water management.
- Published
- 2020
27. Diurnal Timing Dependent Alterations in Gut Microbial Composition Are Synchronously Linked to Salt-Sensitive Hypertension and Renal Damage
- Author
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Saroj Chakraborty, Sarah Galla, Xi Cheng, Blair Mell, Tao Yang, Juthika Mandal, Matam Vijay-Kumar, Beng San Yeoh, Anay Hindupur, Piu Saha, Bina Joe, and Jiyoun Yeo
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Firmicutes ,Blood Pressure ,030204 cardiovascular system & hematology ,Lipocalin ,Gut flora ,Kidney ,Article ,Actinobacteria ,Feces ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,RNA, Ribosomal, 16S ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Circadian rhythm ,Sodium Chloride, Dietary ,Rats, Inbred Dahl ,3-Hydroxybutyric Acid ,Base Sequence ,biology ,Bacteroidetes ,Metabolism ,Diet, Sodium-Restricted ,biology.organism_classification ,Circadian Rhythm ,Gastrointestinal Microbiome ,Rats ,RNA, Bacterial ,030104 developmental biology ,Endocrinology ,Genes, Bacterial ,Hypertension ,Energy Metabolism - Abstract
Alterations of diurnal rhythms of blood pressure (BP) and reshaping of gut microbiota are both independently associated with hypertension. However, the relationships between biorhythms of BP and gut microbial composition are unknown. We hypothesized that diurnal timing-associated alterations of microbial compositions are synchronous with diurnal rhythmicity, dip in BP, and renal function. To test this hypothesis, Dahl salt-sensitive (S) rats on low- and high-salt diets were examined for time of day effects on gut microbiota, BP, and indicators of renal damage. Major shifts in night and day patterns of specific groups of microbiota were observed between the dark (active) and light (rest) phases, which correlated with diurnal rhythmicity of BP. The diurnal abundance of Firmicutes, Bacteroidetes, and Actinobacteria were independently associated with BP. Discrete bacterial taxa were observed to correlate independently or interactively with one or more of the following 3 factors: (1) BP rhythm, (2) dietary salt, and (3) dip in BP. Phylogenetic Investigation of Communities revealed diurnal timing effects on microbial pathways, characterized by upregulated biosynthetic processes during the active phase of host, and upregulated degradation pathways of metabolites in the resting phase. Additional metagenomics functional pathways with rhythm variations were noted for aromatic amino acid metabolism and taurine metabolism. These diurnal timing dependent changes in microbiota, their functional pathways, and BP dip were associated with concerted effects of the levels of renal lipocalin 2 and kidney injury molecule-1 expression. These data provide evidence for a firm and concerted diurnal timing effects of BP, renal damage, and select microbial communities.
- Published
- 2020
28. Reconstitution of the host holobiont in germ-free born male rats acutely increases bone growth and affects marrow cellular content
- Author
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Yuan Tian, Jiyoun Yeo, Sudipta Baroi, Xi Cheng, Beng San Yeoh, Andrew D. Patterson, Matam Vijay-Kumar, Beata Lecka-Czernik, Piu Saha, Bina Joe, Saroj Chakraborty, Rachel M. Golonka, Blair Mell, Piotr J. Czernik, and Ahmed A. Abokor
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Bone Marrow Cells ,Butyrate ,Biology ,Gut flora ,Bone tissue ,Bone Lengthening ,Muscle hypertrophy ,Rats, Sprague-Dawley ,Feces ,Chondrocytes ,Bone Density ,Osteogenesis ,Internal medicine ,RNA, Ribosomal, 16S ,Genetics ,medicine ,Adipocytes ,Coprophagia ,Animals ,Germ-Free Life ,Cell Proliferation ,Bone growth ,Bone Development ,Bacteria ,Host Microbial Interactions ,biology.organism_classification ,Fatty Acids, Volatile ,Gastrointestinal Microbiome ,Rats ,Endocrinology ,medicine.anatomical_structure ,Alkaline phosphatase ,Dysbiosis ,Bone marrow ,Research Article - Abstract
Integration of microbiota in a host begins at birth and progresses during adolescence, forming a multidirectional system of physiological interactions. Here, we present an instantaneous effect of natural, bacterial gut colonization on the acceleration of longitudinal and radial bone growth in germ-free born, 7-wk-old male rats. Changes in bone mass and structure were analyzed after 10 days following the onset of colonization through cohousing with conventional rats and revealed unprecedented acceleration of bone accrual in cortical and trabecular compartments, increased bone tissue mineral density, improved proliferation and hypertrophy of growth plate chondrocytes, bone lengthening, and preferential deposition of periosteal bone in the tibia diaphysis. In addition, the number of small in size adipocytes increased, whereas the number of megakaryocytes decreased, in the bone marrow of conventionalized germ-free rats indicating that not only bone mass but also bone marrow environment is under control of gut microbiota signaling. The changes in bone status paralleled with a positive shift in microbiota composition toward short-chain fatty acids (SCFA)-producing microbes and a considerable increase in cecal SCFA concentrations, specifically butyrate. Furthermore, reconstitution of the host holobiont increased hepatic expression of IGF-1 and its circulating levels. Elevated serum levels of 25-hydroxy vitamin D and alkaline phosphatase pointed toward an active process of bone formation. The acute stimulatory effect on bone growth occurred independently of body mass increase. Overall, the presented model of conventionalized germ-free rats could be used to study microbiota-based therapeutics for combatting dysbiosis-related bone disorders.
- Published
- 2021
29. Immunoglobulin A, an Active Liaison for Host-Microbiota Homeostasis
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Matam Vijay-Kumar, Beng San Yeoh, Connor Campbell, Sreya Brahmandam, Grant H. McDaniel, Ahmed A. Abokor, Rachel M. Golonka, Piu Saha, and Bina Joe
- Subjects
Microbiology (medical) ,Immunoglobulin A ,Gastrointestinal tract ,B cells ,biology ,Host (biology) ,QH301-705.5 ,Review ,Gut flora ,polymeric immunoglobulin receptor (pIgR) ,biology.organism_classification ,Microbiology ,gut homeostasis ,Mucosal immunology ,Antigen ,secretory IgA ,mucosal immunology ,Virology ,Immunology ,biology.protein ,IgA deficiency ,Biology (General) ,Homeostasis - Abstract
Mucosal surfaces in the gastrointestinal tract are continually exposed to native, commensal antigens and susceptible to foreign, infectious antigens. Immunoglobulin A (IgA) provides dual humoral responses that create a symbiotic environment for the resident gut microbiota and prevent the invasion of enteric pathogens. This review features recent immunological and microbial studies that elucidate the underlying IgA and microbiota-dependent mechanisms for mutualism at physiological conditions. IgA derailment and concurrent microbiota instability in pathological diseases are also discussed in detail. Highlights of this review underscore that the source of IgA and its structural form can dictate microbiota reactivity to sustain a diverse niche where both host and bacteria benefit. Other important studies emphasize IgA insufficiency can result in the bloom of opportunistic pathogens that encroach the intestinal epithelia and disseminate into circulation. The continual growth of knowledge in these subjects can lead to the development of therapeutics targeting IgA and/or the microbiota to treat life threatening diseases.
- Published
- 2021
30. Gut Microbiota Accelerates Bone Growth and Marrow Adiposity of the Adolescent Gnotobiotic Rat
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Xi Cheng, Piotr J. Czernik, Matam Vijay-Kumar, Ahmed A. Abokor, Saroj Chakraborty, Jiyoun Yeo, Yuan Tian, Piu Saha, Bina Joe, Sudipta Baroi, Beata Lecka-Czernik, Beng San Yeoh, Andrew D. Patterson, Rachel M. Golonka, and Blair Mell
- Subjects
Bone growth ,medicine.medical_specialty ,Endocrinology ,Internal medicine ,Genetics ,medicine ,Biology ,Gut flora ,biology.organism_classification ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2021
31. I ncreased Host Energy Metabolism in the Proximal Colon‐Microbiota Interface Elevates Blood Pressure
- Author
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Matam Vijay-Kumar, Andrew D. Patterson, Jiyoun Yeo, Xi Cheng, Xue Mei, Yuan Tian, Rachel M. Golonka, Blair Mell, Tao Yang, Saroj Chakraborty, Piu Saha, and Bina Joe
- Subjects
Blood pressure ,Host (biology) ,Chemistry ,Genetics ,Energy metabolism ,Proximal colon ,Molecular Biology ,Biochemistry ,Biotechnology ,Cell biology - Published
- 2021
32. Metabolomics reveal dynamic host responses in lipid, amino acid, and energy metabolism after acute exposure of gut microbiota in germ‐free rats
- Author
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Matam Vijay-Kumar, Beng San Yeoh, Piu Saha, Bina Joe, Xi Cheng, Rachel M. Golonka, Yuan Tian, Andrew D. Patterson, Blair Mell, Jiyoun Yeo, Ahmed A. Abokor, and Saroj Chakraborty
- Subjects
chemistry.chemical_classification ,Host (biology) ,Energy metabolism ,Biology ,Gut flora ,biology.organism_classification ,Biochemistry ,Amino acid ,Metabolomics ,chemistry ,Acute exposure ,Genetics ,Germ ,Molecular Biology ,Biotechnology - Published
- 2021
33. Variability and trends of rainfall using non-parametric approaches: A case study of semi-arid area
- Author
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JAYANTA, DAS, primary, TAPASH, MANDAL, additional, PIU, SAHA, additional, and SUDIP KUMAR, BHATTACHARYA, additional
- Published
- 2021
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34. Enterobactin, an iron chelating bacterial siderophore, arrests cancer cell proliferation
- Author
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Rachel M. Golonka, Beng San Yeoh, Piu Saha, Xia Xiao, Sivarajan Kumarasamy, and Matam Vijay-Kumar
- Subjects
0301 basic medicine ,Siderophore ,Cell Survival ,Iron ,Siderophores ,Antineoplastic Agents ,Apoptosis ,Mitochondrion ,Biochemistry ,Article ,Enterobactin ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Lipocalin-2 ,Escherichia coli ,medicine ,Animals ,Homeostasis ,Cell Proliferation ,Pharmacology ,chemistry.chemical_classification ,Reactive oxygen species ,Chemistry ,Mitochondria ,Cell biology ,Mice, Inbred C57BL ,Deferoxamine ,RAW 264.7 Cells ,030104 developmental biology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer cell ,Reactive Oxygen Species ,Intracellular ,medicine.drug - Abstract
Iron is essential for many biological functions, including being a cofactor for enzymes involved in cell proliferation. In line, it has been shown that cancer cells can perturb their iron metabolism towards retaining an abundant iron supply for growth and survival. Accordingly, it has been suggested that iron deprivation through the use of iron chelators could attenuate cancer progression. While they have exhibited anti-tumor properties in vitro, the current therapeutic iron chelators are inadequate due to their low efficacy. Therefore, we investigated whether the bacterial catecholate-type siderophore, enterobactin (Ent), could be used as a potent anti-cancer agent given its strong iron chelation property. We demonstrated that iron-free Ent can exert cytotoxic effects specifically towards monocyte-related tumor cell lines (RAW264.7 and J774A.1), but not primary cells, i.e. bone marrow-derived macrophages (BMDMs), through two mechanisms. First, we observed that RAW264.7 and J774A.1 cells preserve a bountiful intracellular labile iron pool (LIP), whose homeostasis can be disrupted by Ent. This may be due, in part, to the lower levels of lipocalin 2 (Lcn2; an Ent-binding protein) in these cell lines, whereas the higher levels of Lcn2 in BMDMs could prevent Ent from hindering their LIP. Secondly, we observed that Ent could dose-dependently impede reactive oxygen species (ROS) generation in the mitochondria. Such disruption in LIP balance and mitochondrial function may in turn promote cancer cell apoptosis. Collectively, our study highlights Ent as an anti-cancer siderophore, which can be exploited as an unique agent for cancer therapy.
- Published
- 2019
35. PAD4-dependent NETs generation are indispensable for intestinal clearance of Citrobacter rodentium
- Author
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Vishal Singh, Rachel M. Golonka, Yanming Wang, Matam Vijay-Kumar, Piu Saha, Beng San Yeoh, and Xia Xiao
- Subjects
0301 basic medicine ,Infectious colitis ,Arginine ,Colon ,Hydrolases ,Neutrophils ,Immunology ,Inflammation ,Biology ,Neutrophil extracellular traps ,Extracellular Traps ,Article ,Microbiology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Protein-Arginine Deiminase Type 4 ,Immunity ,medicine ,Citrobacter rodentium ,Immunology and Allergy ,Deoxyribonuclease I ,Animals ,PAD4 ,Mice, Knockout ,Goblet cell ,Innate immune system ,Enterobacteriaceae Infections ,NETs ,Hyperplasia ,medicine.disease ,Bacterial Load ,Immunity, Innate ,3. Good health ,Intestines ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,medicine.symptom ,030215 immunology - Abstract
Peptidyl arginine deiminase-4 (PAD4) is indispensable for generation of neutrophil extracellular traps (NETs), which can provide antimicrobial effects during host innate immune response; however, the role of PAD4 against gastrointestinal infection is largely unknown. Herein, we challenged PAD4-deficient (Pad4-/-) mice and wild-type (WT) littermates with Citrobacter rodentium (CR), and investigated bacteria clearance and gut pathology. Luminal colonization of CR in Pad4-/- mice peaked between 11-14 days post-infection, whereas WT mice suppressed the infection by 14 days. We demonstrated that Pad4-/- mice were unable to form NETs, whereas WT mice showed increased NETs formation in the colon during infection. Pad4-/- mice showed aggravated CR-associated inflammation as indicated by elevated systemic and colonic pro-inflammatory markers. Histological analysis revealed that transmissible colonic hyperplasia, goblet cell depletion, and apoptotic cell death were more pronounced in the colon of CR-infected Pad4-/- mice. Treating WT mice with deoxyribonuclease I, which can disrupt NETs generation, recapitulated the exacerbated CR infection and gut pathology associated with the loss of PAD4. Administration of the PAD4 inhibitor, Cl-amidine also aggravated CR infection, but to a lesser extent. Taken together, our findings highlight the importance of PAD4 in the mucosal clearance of CR and in resolving gut-associated inflammation.
- Published
- 2019
36. Spatio-temporal trend and change point detection of winter temperature of North Bengal, India
- Author
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Jayanta Das, Tapash Mandal, and Piu Saha
- Subjects
010504 meteorology & atmospheric sciences ,Geography, Planning and Development ,0211 other engineering and technologies ,Climate change ,02 engineering and technology ,01 natural sciences ,Computer Science Applications ,Geography ,Artificial Intelligence ,Climatology ,BENGAL ,Rabi crop ,Computers in Earth Sciences ,Winter season ,Change detection ,021101 geological & geomatics engineering ,0105 earth and related environmental sciences - Abstract
The trend of temperature and homogeneity are the most significant issue for climate change allied research. This research aims to identify the long-term trend and change point detection of winter maximum (tmax), minimum (tmin) and average (tmean) temperature of six meteorological stations of North Bengal, India using 102 years’ time series data (1915–2016). To detect the monotonic trend and the rate of change, non-parametric Mann–Kendall (MK) test and Sen’s slope estimator were used. Homogeneity of winter temperature was studied using Buishand’s range test (B test) and Pettit’s test (P test). From the results, it was observed that most of the stations were showed significant (P
- Published
- 2019
37. Sterile neutrophilia induced via CXCR4 antagonism ameliorates colonic inflammation by increasing immunosuppressive regulatory T cells
- Author
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Piu Saha, Beng San Yeoh, Rachel Golonka, Ahmed Abokor, and Matam Vijay-Kumar
- Subjects
Immunology ,Immunology and Allergy - Abstract
Sterile neutrophilia (SN) is commonly associated with chronic disease, but its role in inflammatory bowel diseases (IBD) is largely unknown. AMD3100 (plerixafor; AMD) is a CXCR4 antagonist that promotes neutrophil egress from bone marrow resulting in SN. To study the role of SN in IBD, we induced chronic intestinal inflammation in C57BL6 mice via 4 weekly injections of IL-10R neutralizing antibody and administered AMD (10 mg/kg bw, i.p., twice weekly) or vehicle. As expected, AMD-treated control and colitic mice had increased peripheral and splenic neutrophils. AMD treatment remarkably reduced epithelial damage and hyperplasia, immune cell infiltration, and disease activity index. To elucidate the protective mechanism, we analyzed immune cells in peripheral circulation, spleen and lamina propria. In circulation, colitic mice with AMD treatment had elevated % CD3+CD4+ helper T cells (Th) but reduced % CD3+CD8+ cytotoxic T (Tc) cells. Yet, the % CD3+CD4+FoxP3+ cells (Tregs) and % CD3+CD4+RORγt+ cells (Th17) remained unchanged. In spleen, AMD treatment significantly increased Tregs, but decreased Th and Tc cells. In lamina propria, AMD treatment markedly elevated Tregs, including RORγt+ Tregs and tolerogenic IL-10+ Tregs. Conversely, the inflammatory IL-17+ Th cells were decreased in AMD-treated colitic mice. In addition to the immunosuppressive milieu, AMD-treated colitic mice had increased ileal expression of the antimicrobial peptide angiogenin 4, which further suggests SN to be important in maintaining gut microbiota homeostasis. Collectively, our results demonstrate that SN could be an adaptive and beneficial immune response during chronic intestinal inflammation. This research was funded by R01 grant from the National Institutes of Health (NIH) [grant number CA219144] and Crohn’s and Colitis Foundation (CCF) [grant number 855256].
- Published
- 2022
38. Dynamics of antimicrobial protein secretion in mouse milk
- Author
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Ahmed Abokor, Piu Saha, Beng San Yeoh, Rachel Golonka, and Matam Vijay-Kumar
- Subjects
Immunology ,Immunology and Allergy - Abstract
Breast milk is the preferred food for the newborns and considered as complete ‘edible immune system’. In addition, breast milk is a source of innate and adaptive proteins which not only protects the naïve infant gastrointestinal tract from enteropathogens but also aid in the appropriate initial colonization of gut microbiota. In this study, we analyzed antimicrobial immune proteins in the milk from C57BL/6 dams at several time points, and observed distinctive patterns in the immune protein levels throughout the lactation period. The presence of innate immune proteins serum amyloid A (SAA), CD14, and notably lipocalin-2 (Lcn2) were observed in high quantities with Lcn2 and SAA present at microgram levels suggesting a potential niche for these proteins during neonatal immune development. Moreover, low dose LPS administration to dams significantly increased some of these proteins in the milk. In addition, adaptive immune proteins immunoglobulins (Ig) A and G with IgG were present in milk at higher quantities compared to IgA at day 5 post-delivery. Interestingly, class-switching occurs by day 15 indicating a selective adaptive immune preference towards IgA, which could be due to gut colonization of newborns with more complex gut microbiota with aging and IgA being a major gut homeostatic factor. Additionally, milk from IgA-deficient dams allowed for robust proliferation of E. coli compared to wild-type milk further signifying the potential involvement of IgA during the early colonization of microbes in the neonatal gut. Collectively, our findings provide insight in the various immune proteins with antimicrobial activity may play a major role in the initial microbial colonization in the gut, which has long-lasting consequences on the host. Supported by NIH R01-CA219144, NCI Diversity Supplement (CA219144-05S1)
- Published
- 2022
39. The bacterial siderophore enterobactin confers survival advantage to Salmonella in macrophages
- Author
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Matam Vijay-Kumar, Bhuvana Katkere, Girish S. Kirimanjeswara, Piu Saha, Beng San Yeoh, Xia Xiao, and Qiuyan Chen
- Subjects
inorganic chemicals ,0301 basic medicine ,Microbiology (medical) ,Siderophore ,Salmonella ,medicine.disease_cause ,Microbiology ,Iron chelation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Enterobactin ,polycyclic compounds ,otorhinolaryngologic diseases ,medicine ,Survival advantage ,biology ,Gastroenterology ,biology.organism_classification ,Enterobacteriaceae ,030104 developmental biology ,Infectious Diseases ,chemistry ,030211 gastroenterology & hepatology ,Bacteria - Abstract
Enterobactin (Ent), a prototypical bacterial siderophore known for its unparalleled affinity for iron, is widely conserved among members of the Enterobacteriaceae family of Gram-negative bacteria. ...
- Published
- 2018
40. FPR-1 (Formyl Peptide Receptor-1) Activation Promotes Spontaneous, Premature Hypertension in Dahl Salt-Sensitive Rats
- Author
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Emily W. Waigi, Shaunak Roy, Nicole R. Bearss, Matam Vijay-Kumar, Sarah Galla, Piu Saha, Camilla F Wenceslau, Jonnelle M Edwards, Bina Joe, Jeremy C Tomcho, Blair Mell, Xi Cheng, and Cameron G. McCarthy
- Subjects
0301 basic medicine ,Dahl Salt-Sensitive Rats ,medicine.medical_specialty ,Blood Pressure ,030204 cardiovascular system & hematology ,Mitochondrion ,Vascular Remodeling ,Bacterial Physiological Phenomena ,Formyl peptide receptor 1 ,Article ,Vascular remodelling in the embryo ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Sodium Chloride, Dietary ,Rats, Inbred Dahl ,Cell Death ,Chemistry ,Receptors, Formyl Peptide ,Gastrointestinal Microbiome ,Mitochondria ,Rats ,030104 developmental biology ,Endocrinology ,Hypertension - Abstract
Cell death has long been a characteristic phenotype of organ damage in hypertension, and recently, leaky gut has been revealed as a novel hypertensive phenotype. However, despite the increase in bacterial and damaged mitochondrial products in the circulation of hypertensive patients and animals, the mechanistic contribution of these two phenomena to hypertension pathophysiology is unknown. Mitochondria and bacteria both start protein translation with an N-formyl methionine residue and thus are the only sources of NFPs (N-formyl peptides), which activate the FPR-1 (formyl peptide receptor-1). We hypothesized that the synergistic action of bacterial and mitochondrial NFPs would cause the spontaneous elevation of blood pressure and vascular remodeling in male Dahl salt-sensitive rats via FPR-1. We observed that mitochondria-derived peptides originating from cell death in the kidneys are responsible for FPR-1–induced vascular hypercontractility and remodeling and premature elevation of BP in Dahl salt-sensitive rats fed a low-salt diet. However, a high-salt diet leads to gut barrier disruption and, subsequently, a synergistic action of mitochondria, and bacteria-derived leaky gut NFPs lead to a severe and established hypertension. Administration of an FPR-1 antagonist lowered blood pressure in Dahl salt-sensitive rats on a low-salt diet but amoxicillin administration did not. These results reveal for the first time that cell death can be a cause of hypertensive pathophysiology, whereas leaky gut is a consequence.
- Published
- 2021
41. Innate Immune Cells and Hypertension: Neutrophils and Neutrophil Extracellular Traps (NETs)
- Author
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Matam Vijay-Kumar, Piu Saha, Bina Joe, Cameron G. McCarthy, Camilla F Wenceslau, and Rachel M. Golonka
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0301 basic medicine ,Neutrophils ,T cell ,030204 cardiovascular system & hematology ,Gut flora ,Extracellular Traps ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,medicine ,Animals ,Humans ,Inflammation ,Innate immune system ,biology ,business.industry ,SARS-CoV-2 ,COVID-19 ,Neutrophil extracellular traps ,biology.organism_classification ,Immunity, Innate ,Gastrointestinal Microbiome ,Oxidative Stress ,030104 developmental biology ,medicine.anatomical_structure ,Blood pressure ,Neutrophil elastase ,Immunology ,Hypertension ,biology.protein ,business ,Homeostasis - Abstract
Uncontrolled immune system activation amplifies end-organ injury in hypertension. Nonetheless, the exact mechanisms initiating this exacerbated inflammatory response, thereby contributing to further increases in blood pressure (BP), are still being revealed. While participation of lymphoid-derived immune cells has been well described in the hypertension literature, the mechanisms by which myeloid-derived innate immune cells contribute to T cell activation, and subsequent BP elevation, remains an active area of investigation. In this article, we critically analyze the literature to understand how monocytes, macrophages, dendritic cells, and polymorphonuclear leukocytes, including mast cells, eosinophils, basophils, and neutrophils, contribute to hypertension and hypertension-associated end-organ injury. The most abundant leukocytes, neutrophils, are indisputably increased in hypertension. However, it is unknown how (and why) they switch from critical first responders of the innate immune system, and homeostatic regulators of BP, to tissue-damaging, pro-hypertensive mediators. We propose that myeloperoxidase-derived pro-oxidants, neutrophil elastase, neutrophil extracellular traps (NETs), and interactions with other innate and adaptive immune cells are novel mechanisms that could contribute to the inflammatory cascade in hypertension. We further posit that the gut microbiota serves as a set point for neutropoiesis and their function. Finally, given that hypertension appears to be a key risk factor for morbidity and mortality in COVID-19 patients, we put forth evidence that neutrophils and NETs cause cardiovascular injury post-coronavirus infection, and thus may be proposed as an intriguing therapeutic target for high-risk individuals. © 2021 American Physiological Society. Compr Physiol 11:1575-1589, 2021.
- Published
- 2021
42. Rainfall Insight in Bangladesh and India: Climate Change and Environmental Perspective
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Jayanta Das, Piu Saha, A. T. M. Sakiur Rahman, and Tapash Mandal
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Irrigation ,Trend analysis ,Flood myth ,Dry season ,medicine ,Climate change ,Environmental science ,Physical geography ,Precipitation ,Seasonality ,Monsoon ,medicine.disease - Abstract
The analysis of detail characteristics of rainfall can be used to make a better decision for the availability of water, irrigation, agricultural water management as well as quality of life. Therefore, this study investigated details characteristics of rainfall in Bangladesh and India from 1951 to 2015. Rainfall features like Seasonality Index (SI) and Precipitation Concentration Index (PCI) were estimated to characterize spatial pattern of rainfall and Innovative Trend Analysis (ITA), Mann-Kendall (MK) and modified Mann-Kendall (mMK) test were used to detect trend in the data. Moreover, Sen’s slope (Q) estimator was used to calculate the magnitude of changes. Obtained rainfall seasonality index revealed that rainfall for the major portion of Bangladesh was markedly seasonal with a long dry season (SI= 0.80-0.99) with irregular distribution pattern (PCI = 16–20%). But in India, most of rainfall occurs in less than 3 months (SI = 1.00–1.19) with strong irregularity (PCI= >20%). Besides, most of the stations in Bangladesh showed increasing trends (60%) in annual rainfall, among them 33.33% were statistically significant (α = 0.05). However, India was dominated by significant decreasing trend (66.66%) for annual rainfall. For seasonal rainfall, pre-monsoon rainfall dominated by increasing trend (70%), on the other hand, both increasing and decreasing trend were found in monsoon, post-monsoon and winter rainfall in Bangladesh. Conversely, both positive and negative trend was observed in pre-monsoon, monsoon and post-monsoon rainfall in India with dominated decreasing trend (91%) in winter rainfall. The results of the ITA also showed more or less similar results which confirmed the reliability of this new method. The results of detail analysis of rainfall will be helpful for policymakers and scientist to focus on regional scale planning about water sharing, flood and drought situation between the country that will ultimately helpful for agricultural development and environmental planning.
- Published
- 2020
43. Abstract P150: Concerted Diurnal Rhythms Of Gut Microbiota With Salt-sensitive Hypertension And Renal Damage
- Author
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Anay Hindupur, Beng San Yeoh, Sarah Galla, Saroj Chakraborty, Blair Mell, Jiyoun Yeo, Xi Cheng, Tao Yang, Matam Vijay Kumar, Piu Saha, Bina Joe, and Juthika Mandal
- Subjects
Kidney ,Renal damage ,Physiology ,Biology ,Gut flora ,biology.organism_classification ,Diurnal rhythms ,Holobiont ,medicine.anatomical_structure ,Salt sensitivity ,Internal Medicine ,medicine ,Microbiome ,Circadian rhythm - Abstract
Circadian, diurnal rhythm is a vital physiological feature of life forms, which enables holobionts to adapt to the day and night cycles. Evidence suggests that both factions of the holobiont, i.e, the host and its microbiota demonstrate physiological circadian rhythms. Blood pressure is a good example of a host physiological feature with a well-defined diurnal rhythm. In a healthy human, blood pressure (BP) rises to its peak during awakening morning hours and declines to the lowest level during night. In salt-sensitive hypertension, aberrant diurnal rhythms of BP and gut dysbiosis have been demonstrated. Given the critical role of gut microbiota in BP regulation, our current objective was to investigate whether there are synchronous rhythms of holobiont in rodents on low salt and high salt diets and if inflammation pattern also changes diurnally. We examined Dahl Salt-Sensitive (S) rats on low (0.3%) and high (2%) salt diets and BP and inflammation pattern was checked. As hypothesized, both microbiota and kidney inflammation showed diurnal rhythm in response to low salt and high salt diet. Major shifts in diurnal patterns of specific groups of microbiota were observed between the dark (active) and light (rest) phases, which correlated with the diurnal rhythmicity of BP. Diurnal rhythms of Firmicutes, Bacteroidetes and Actinobacteria were independently associated with BP. Discrete bacterial taxa were observed to correlate independently or interactively with one or more of the following 3 factors- 1) BP rhythm, 2) dietary salt, 3) amplitude of BP. PICRUSt analysis revealed diurnal rhythmicity of microbial pathways, characterized by microbiota upregulated biosynthetic processes during active phase and upregulated degradation pathways of metabolites in resting phase. These diurnal changes in microbiota, their functional pathways and BP amplitude were associated with concerted rhythmicity of renal Lipocalin 2 and Kim1 expression and circulating β-hydroxybutyrate in high salt S rats. Such concerted rhythmicity of holobiont with peak of changes at active phase of salt hypertension suggests that targeting this timepoint to reshape microbiota and/or intervene with medication could efficiently benefit the hypertensives
- Published
- 2020
44. Abstract P149: Germ-free Rats Reveal An Obligatory Role Of Microbiota In Blood Pressure
- Author
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Jiyoun Yeo, Tao Yang, Juthika Mandal, Matam Vijay Kumar, Camilla F Wenceslau, Piu Saha, Rachel M. Golonka, Bina Joe, Blair Mell, Cam McCarthy, Beng San Yeoh, Xi Cheng, and Saroj Chakraborty
- Subjects
Blood pressure ,business.industry ,Internal Medicine ,Medicine ,Physiology ,Microbiome ,Risk factor ,business ,digestive system ,Elevated blood - Abstract
Elevated blood pressure or hypertension is the single largest risk factor for cardiovascular diseases which are the leading cause of human deaths. Current clinical management of blood pressure is focused on restoring homeostasis of the host alone, without accounting for commensal gut microbiota. Recent evidence from the CARDIA study in humans and multiple studies using animal models suggest that development of hypertension in the host is associated with alterations in microbiotal communities. Here we examined whether microbiota is necessary for blood pressure and vascular homeostasis by functional evaluation of the gut homeostasis, hemodynamic, and vascular function of gnotobiotic rats reconstituted with microbiota to represent the complete holobiont. Gnotobiotic rats were used to represent incomplete holobionts. To reconstitute complete holobionts, gnotobiotic rats were co-housed with conventionally-raised rats. Acquisition of microbiota was evaluated through monitoring of gross ceca and fecal samples by metagenomic 16S sequencing. BP was recorded and vascular, renal, hepatic, cardiac and gut features were assessed using histology and ex vivo myography. Markers of innate immune effectors (Immune cell population, level of Lcn2, Gut permeability) were used to examine the nature and extent of host immune cell processes concomitantly occurring along with observations of host hemodynamics. Compared to the reconstituted holobiont represented by the animals exposed to microbiota, the incomplete-holobiont represented by gnotobiotic rats, had significantly lower BP (SBP of germ free:109±8 mmHg, SBP of conventionalized:138±10mmHg * ) and vascular contractility responses to phenylephrine (Emax (mN): germ-free: 6.9±1.3, GFC: 11.7±0.7*). Acute exposure of the host to microbiota reconstituted gut microbiotal communities, significantly boosted their gut epithelial cell proliferation, innate immune function and restored vascular contractility. These data indicate that in addition to the dependency of the host on microbiota for essential bodily functions such as digestion of plant-derived complex carbohydrates, the host is also dependent on microbiota for maintaining blood pressure and vascular function
- Published
- 2020
45. Abstract P238: Bile Acid Metabolites Modulate Hypertension
- Author
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Juthika Mandal, Cam McCarthy, Camilla F Wenceslau, Katie A. Meyer, Wei Jia, Vasanta Putluri, Matam Vijay Kumar, Jiyoun Yeo, Nagireddy Putluri, Piu Saha, Bina Joe, Anju Lulla, Blair Mell, Arun Sreekumar, Beng San Yeoh, Ahmad Alimadadi, Saroj Chakraborty, and Xi Cheng
- Subjects
Blood pressure ,Bile acid ,medicine.drug_class ,business.industry ,Internal Medicine ,medicine ,Physiology ,Disease ,Microbiome ,Risk factor ,medicine.disease ,business ,Stroke - Abstract
Hypertension is the single prominent risk factor of epidemic proportions leading to cardiovascular disease and stroke, which comprise the top two reasons for mortality of humans in the modern age. Much of the attention for the unknown causes of hypertension was focused on genetics and dietary salt, but in recent years, host-microbiotal interaction is gaining importance. Host-microbiotal partnership is key for the generation of many bioactive molecules including bile acid (BA) metabolites. Primary bile acids are synthesized and conjugated by the host but deconjugated and further modified to secondary BA by gut commensal bacteria. BA metabolites serve as important ligands for host nuclear receptors and/or G-protein-coupled receptors. These receptors have pivotal roles in blood pressure regulation. However, the effect of the host-microorganism biliary network on blood pressure (BP) remains poorly characterized. Here we report that both dietary salt and genetic factors rewire the composition of bile acids and BP. Specific reductions in conjugated bile acids were noted in human hypertensives as well as in rats with hypertension. Conjugation of bile acids by the host alone, devoid of the deconjugation step by microbiota, was sufficient to decrease BP of germ-free rats compared to germ-free conventionalized rats. Nutritional restoration of the conjugation of bile acids with Taurine increased the availability of circulating conjugated bile acids as ligands and ameliorated host susceptibility to hypertension via BA nuclear receptors and G-protein-coupled receptors. Thus, hosts and their bacterial symbionts can control host BP homeostasis via the resulting pool of bile acid metabolites. Sources of funding: National Institutes of Health (R01HL143082).
- Published
- 2020
46. Abstract 22: Formyl Peptide Receptor-1 Activation Is Crucial For The Cause Of Spontaneous Hypertension In Dahl Salt Sensitive Rats
- Author
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Matam Vijay-Kumar, Camilla F Wenceslau, Jonnelle M Edwards, Piu Saha, Bina Joe, Xi Cheng, Sarah Galla, Blair Mell, Nicole R. Bearss, and Cam McCarthy
- Subjects
Dahl Salt-Sensitive Rats ,Biochemistry ,biology ,Chemistry ,Internal Medicine ,Microbiome ,Mitochondrion ,biology.organism_classification ,Bacteria ,Formyl peptide receptor 1 - Abstract
Mitochondria evolved from bacteria and use N-formylated peptides (NFPs) to synthetize protein. Bacterial and mitochondrial NFPs activate formyl peptide receptor 1 (FPR-1) and lead to vascular injury. We previously observed that Dahl Salt Sensitive rats (S) fed a low-salt (LS, 0.3% NaCl) diet presented spontaneous hypertension, vascular dysfunction, and overexpression of FPR-1 in arteries when compared to Dahl Salt Resistant (R) rats. High salt (HS, 2% NaCl) diet worsened these phenotypes in S rats. Interestingly, HS diet induced leaky gut and amoxicillin (AMO) treatment decreased BP in S-HS. Due to the dual sources of NFPs (microbiota and host mitochondria), we hypothesized that cell death-derived mitochondria and/or leaky gut-derived bacterial NFPs lead to FPR-1 activation, vascular injury and elevated BP in S rats independent of HS diet. For this, we used flow cytometry to measure cell necrosis and early and late apoptosis in kidney, bone marrow-derived macrophages and mesenteric resistance arteries (MRA) from male S and R rats (8-week old) on a LS diet. Zonulin, a biomarker for leaky gut, was measured in plasma. In another group, rats were treated with FPR-1 antagonist [Cyclosporin H (CsH), 0.3 mg/kg/day, osmotic mini-pump, 14 days], vehicle (VEH) or received water with AMO (5 mg/kg/day) for 21 days to deplete bacteria. BP was measured by telemetry and vascular function and structure were assessed in MRA. S rats presented increased kidney cell necrosis (R: 3.8±0.3 vs. S: 5.3±0.5* %). CsH decreased spontaneous elevation of BP [Diastolic: R+VEH: 77±2.7 vs. R+CsH: 81±1.2 vs. S+VEH: 126±3.0* vs. S+CsH:115±2.7 # ] and vascular hypercontractility [KCl (120mM): R+VEH: 9.4±1 vs. R+CsH: 10.2±0.4; S+VEH: 15.5±0.9* vs. S+CsH:11.7±0.8 # mN; Phenylephrine (10μM): R+VEH: 9.3±1 vs. R+CsH: 9.7±1; S+VEH: 14.5±1*vs. S+CsH: 11.4±0.6 # mN) in S-LS rats. AMO did not change vascular contraction or BP. Leaky gut was not observed in Dahl S-LS diet. In conclusion, FPR-1 can serve as a causative agent for the spontaneous elevation of BP and kidney-derived mitochondria, but not gut-derived microbiota, are the main source for NFPs.
- Published
- 2020
47. Abstract P112: Elevated Blood Pressure In Conventionalized Germ-free Rats Is Coupled With Upregulation Of Kynurenic Pathway Metabolites And Central Immune Responses
- Author
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Vasanta Putluri, Jiyoun Yeo, Guannan Zhou, Arun Sreekumar, Camilla F Wenceslau, Nagireddy Putluri, Tao Yang, Xue Mei, Rachel M. Golonka, Danthasinghe Waduge Badrajee Piyarathna, Xi Cheng, Piu Saha, Bina Joe, Blair Mell, Juthika Mandal, Beng San Yeoh, Matam Vijay-Kumar, Saroj Chakraborty, and Cameron G. McCarthy
- Subjects
medicine.medical_specialty ,Chemistry ,Metabolite ,Tryptophan ,Metabolism ,Kynurenate ,chemistry.chemical_compound ,Endocrinology ,Immune system ,medicine.anatomical_structure ,nervous system ,Downregulation and upregulation ,Internal medicine ,Internal Medicine ,medicine ,Microbiome ,Nucleus - Abstract
Background: Recent evidence supports that metabolic dysfunction underlies hypertension. Injection of kynurenate, a metabolite of tryptophan pathway, into the paraventricular nucleus of the hypothalamus (PVN) lowers blood pressure (BP). Intestinal absorption and metabolism of tryptophan are impacted by gut microbiota. Since gut-brain axis contributes to gut dysbiosis-inducd hypertension, we hypothesized that gut microbiota modulates the levels of kynurenic pathway metabolites that have central impact on BP regulation. Methods: We, for the first time, used 7 weeks old male Germ-free (GF) Spague Dawley (SD) rats (n=5) and GF rats co-housed with conventional SD rats for 10 days (GFC) (n=6). BP was measured by tail-cuff. Serum metabolites were quantified by 6495 triple quandrople mass spectrometryand data was normalized using isotoplic labelled compounds. The nucleus of the solitary tract (NTS), the principal sensory nucleus for peripheral changes, and the PVN, a relay center projecting sympathetic output based on the integrated afferent inputs from brain regions including NTS, were analyzed by microarray hybridization for mRNA expression. Results: Compared to the GF rats, GFC rats had significantly higher systolic (139 mmHg vs 115 mmHg, p p p p Cd74, Il1b, Cxcl1, Mmp14 ) in the PVN (gene ontology analysis, p Sox11, Tp53, Cdk6, Hoxb4, Foxo4, Cyr61 ) in the NTS (gene ontology analysis, p Conclusion: Colonization of gut microbiota in GF rats induced increased cell differentiation and synaptic plasticity in the NTS and immune responses in the PVN, indicating the restructured sensory neurons of the NTS and enhanced sympathetic output from the PVN. These are in line with increased levels of kynurenic acid and 3-hydroxy kynurenine, and BP, respectively, suggesting that BP regulation by the gut-brain axis may be mediated by kynurenic pathway.
- Published
- 2020
48. Meteorological drought analysis using Standardized Precipitation Index over Luni River Basin in Rajasthan, India
- Author
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Piu Saha, Amiya Gayen, Jayanta Das, and Sudip Kumar Bhattacharya
- Subjects
geography ,geography.geographical_feature_category ,Rain gauge ,General Chemical Engineering ,General Engineering ,Drainage basin ,General Physics and Astronomy ,Climate change ,Structural basin ,Water resources ,Trend analysis ,General Earth and Planetary Sciences ,Environmental science ,General Materials Science ,Physical geography ,Precipitation ,Precipitation index ,General Environmental Science - Abstract
The study aimed to monitor the spatial extent and severity of drought events in the Luni River Basin using Standardized Precipitation Index (SPI), and hence, the long-term monthly precipitation records of 39 rain gauge stations (1973–2016) were used in the study. Both the long-term (24, 12, and 9 months) and short-term (6, 3, and 1 month) SPI were calculated to recognize the drought events and the percentage of the area covered by the severe drought conditions. The nonparametric Mann–Kendall test was performed for trend analysis in drought events to investigate the consistency of drought events. The frequency results of drought events revealed that Jalore station was the highest drought frequency station, while the lowest drought frequency was observed in Vijaynagar station. The annual SPI result showed that the following years witnessed major drought events: 1981, 1984, 1985, 1988, 1989, 1991, 1993, 1999, 2000, 2004, 2005, and 2008. Besides, the results of the Mann–Kendall test showed that a substantial portion of the eastern basin experienced an increase in the intensity of drought, while the western basin experienced a decrease in the severity of the drought. The comprehensive analysis is indicative of climate change, and there is a possibility that such droughts would become more common in the future in the Luni River Basin. The results of this study would help planners to develop sound policy on water resources and also assist in forecasting systems to provide advance warnings.
- Published
- 2020
49. Reconstitution of the host holobiont in germ-free rats acutely increases bone growth and affects marrow cellular content
- Author
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Beata Lecka-Czernik, Rachel M. Golonka, Blair Mell, Sudipta Baroi, Matam Vijay-Kumar, Saroj Chakraborty, Jiyoun Yeo, Beng S Yeoh, Ahmed A. Abokor, Xie Cheng, Piu Saha, Bina Joe, and Piotr J. Czernik
- Subjects
Bone growth ,medicine.medical_specialty ,biology ,Butyrate ,Gut flora ,Bone tissue ,biology.organism_classification ,medicine.disease ,Bone Lengthening ,medicine.anatomical_structure ,Endocrinology ,Internal medicine ,medicine ,Alkaline phosphatase ,Bone marrow ,Dysbiosis - Abstract
In recent years there has been growing evidence regarding the effect of microbiota on the skeletal growth and homeostasis. Here we present, for the first time, accelerated longitudinal and radial bone growth in young (7-week-old) germ-free male rats after short-term exposure to a newly established gut microbiota. Changes in bone mass and structure were analyzed after 10 days following the onset of colonization through cohousing with conventional rats and revealed unprecedented acceleration of bone accrual in cortical and trabecular compartments, increased bone tissue mineral density, improved proliferation and hypertrophy of growth plate chondrocytes, bone lengthening, and preferential deposition of periosteal bone in tibia diaphysis. In addition, the number of small-in-size adipocytes increased, while the number of megakaryocytes decreased, in the bone marrow of conventionalized germ-free rats. The observed changes in bone status were paralleled with a positive shift in microbiota composition towards short chain fatty acids (SCFA)-producing microbes, which reflected a dramatic increase in cecal concentration of SCFA, specifically butyrate. Further, reconstitution of the host holobiont increased hepatic expression of IGF-1 and its circulating levels, implicating an involvement of the somatotropic axis. Increased serum levels of 25-hydroxy vitamin D and alkaline phosphatase pointed toward an active process of bone formation. The acute stimulatory effect on bone growth occurred independently of body mass increase and resembled reversal of dysbiosis in adolescence, which is marked by rapid skeletal expansion. These findings may help in developing microbiota-based therapeutics to combat bone related disorders resulting from hormonal defects and/or malnutrition in children and adolescence.
- Published
- 2020
50. Gnotobiotic Rats Reveal That Gut Microbiota Regulates Colonic mRNA of Ace2 , the Receptor for SARS-CoV-2 Infectivity
- Author
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Andrew T. Gewirtz, Jiyoun Yeo, Cameron G. McCarthy, Xi Cheng, Xue Mei, Camilla F Wenceslau, Saroj Chakraborty, Arun Sreekumar, Rachel M. Golonka, Nagireddy Putluri, Beng San Yeoh, Guannan Zhou, Blair Mell, Danthasinghe Waduge Badrajee Piyarathna, Piu Saha, Bina Joe, Matam Vijay-Kumar, Juthika Mandal, Vasanta Putluri, and Tao Yang
- Subjects
Infectivity ,Regulation of gene expression ,Messenger RNA ,RNA ,Biology ,Gut flora ,biology.organism_classification ,medicine.disease ,Microbiology ,Internal Medicine ,medicine ,Colitis ,Receptor ,Betacoronavirus - Published
- 2020
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