Browsing by Author "Senapati, Sabyasachi"

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Celiac disease poses significant risk in developing depression, anxiety, headache, epilepsy, panic disorder, dysthymia: A�meta-analysis
(Springer, 2021-11-28T00:00:00) Sharma, Nidhi; Singh, Kavita; Senapati, Sabyasachi
Celiac disease (CD) primarily affects the small intestine. Previous studies have identified higher incidences of neuropsychiatric diseases among CD patients compared to non-CD controls. Genome-wide association studies have identified >60 non-human leukocyte antigen (HLA) genes associated with CD, where estimated 15% genes have role in neurological health. We carried out a systematic review and meta-analysis to estimate the potential risk conferred by CD in developing neuropsychiatric diseases. Literature search was performed till June 2019. Incidences of neuropsychiatric diseases were compared among CD and non-CD controls. Funnel plots and Egger�s tests were used to evaluate publication bias and estimate study effects. Qualities of the included studies were estimated using Newcastle-Ottawa Scale. Quality of evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Odds of developing neuropsychiatric diseases among CD were evaluated by computing meta-odds ratio (Manten-Haenszel method) and Z test p-value using random and fixed effect�models based on the degree of study heterogeneity. Thirteen non-randomized case-control studies were found eligible. Subjects suffering from CD were found to have significantly more risk to develop depression (p<1.00E-05; OR=1.60 [1.37�1.86]), anxiety (p=0.05; OR=1.41 [1.00�1.97]), headache (p<0.1.00E-05; OR=3.27 [2.46�4.34]), epilepsy (p<1.00E-04; OR=11.90 [3.78�37.43]), panic disorder (p<1.00E-04; OR=4.64 [2.22�9.70]), and dysthymia (p=2.00E-03; OR=5.27 [1.83�15.22]). CD is a major predisposing factor in developing array of common neuropsychiatric diseases. Shared biological processes and molecular networks could play a crucial role in disease co-occurrence. Detailed molecular evidences are needed to establish the cause-effect relationship between these diseases. � 2021, Indian Society of Gastroenterology.
Celiac disease-associated loci show considerable genetic overlap with neuropsychiatric diseases but with limited transethnic applicability
(Springer, 2023-01-10T00:00:00) Sharma, Nidhi; Banerjee, Pratibha; Sood, Ajit; Midha, Vandana; Thelma, B.K.; Senapati, Sabyasachi
Clinical and public health research has revealed the co-occurrence of several neuropsychiatric diseases among patients with celiac disease (CD). The significant presence of CD-specific autoantibodies in patients with neuropsychiatric diseases and vice versa are often reported. To explain the genetic basis of such frequent disease co-occurrence and investigate the underlying common pathways/processes, we performed an extensive cross-disease association study followed by supporting in silico functional validation of the leads. Genomewide association study (GWAS) data for CD and eight commonly co-occurring neuropsychiatric diseases from Caucasian populations were analysed, and the shared loci were determined. We performed Immunochip-based fine mapping of these overlapping association signals in an independent European CD data and tested their cross-ethnic transferability using CD association data from the genetically distinct north Indian population. This study identified 12 shared loci between the two diseases with genomewide significance (P ? 5e-8). Of these five loci, namely NFIA, KIA1109, NOTCH4-TSBP1-PBX2, HLA-DQA1 and CSK replicated in an independent Dutch cohort representing European ancestry. Three of these loci, namely NFIA, NOTCH4-TSBP1-PBX2 and HLA-DQA1 that are common between CD, anxiety, migraine and schizophrenia respectively withstood locus transferability test in north Indians. Tissue-specific eQTL analysis of SNPs from transferable loci revealed expression QTL effects in brain tissue besides the small intestine and whole blood. Pathway analysis and evidence of epigenetic regulation highlighted the potential contribution of these SNPs to disease pathology. The replicable and transferable association of genetic variants from MHC locus and their functional implications suggest the process of antigen presentation and adaptive/innate immune response regulated by non-HLA genes in the locus may dominate the shared pathogenesis of CD and neuropsychiatric diseases. Functional validation of the shared candidate genes is warranted to unravel the molecular mechanism for the co-occurrence of CD and specific neuropsychiatric diseases. � 2023, Indian Academy of Sciences.
Components of IGF-axis in growth disorders: a systematic review and patent landscape report
(Springer, 2022-05-06T00:00:00) Singh, Amit; Pajni, Ketan; Panigrahi, Inusha; Dhoat, Navdeep; Senapati, Sabyasachi; Khetarpal, Preeti
Purpose: In this review, epi/genetic mutations of IGF-axis components associated with growth disorders have been summarized alongwith assessment of relevant diagnostic and therapeutic technology through patent literature. Methodology: PROSPERO protocol registration CRD42021279468. For scientific literature search Literature databases (PubMed, EMBASE, ScienceDirect, and Google Scholar) were queried using the appropriate syntax. Various filters were applied based on inclusion and exclusion criteria. Search results were further refined by two authors for finalizing studies to be included in this synthesis. For patent documents search Patent databases (Patentscope and Espacenet) were queried using keywords: IGF or IGFBP. Filters were applied according to International Patent Classification (IPC) and Cooperative Patent Classification (CPC). Search results were reviewed by two authors for inclusion in the patent landscape report. Results: For scientific literature analysis, out of 545 search results, 196 were selected for review based on the inclusion criteria. For Patent literature search, out of 485 results, 37 were selected for this synthesis. Conclusion: Dysregulation of IGF-axis components leads to various abnormalities and their key role in growth and development suggests epi/mutations or structural defects among IGF-axis genes can be associated with growth disorders and may explain some of the idiopathic short stature cases. Trend of patent filings indicate advent of recombinant technology for therapeutics. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Contributions of human ACE2 and TMPRSS2 in determining host�pathogen interaction of COVID-19
(Springer, 2021-02-25T00:00:00) Senapati, Sabyasachi; Banerjee, Pratibha; Bhagavatula, Sandilya; Kushwaha, Prem Prakash; Kumar, Shashank
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is at present an emerging global public health crisis. Angiotensin converting enzyme 2 (ACE2) and trans-membrane protease serine 2 (TMPRSS2) are the two major host factors that contribute to the virulence of SARS-CoV-2 and pathogenesis of coronavirus disease-19 (COVID-19). Transmission of SARS-CoV-2 from animal to human is considered a rare event that necessarily requires strong evolutionary adaptations. Till date no other human cellular receptors are identified beside ACE2 for SARS-CoV-2 entry inside the human cell. Proteolytic cleavage of viral spike (S)-protein and ACE2 by TMPRSS2 began the entire host�pathogen interaction initiated with the physical binding of ACE2 to S-protein. SARS-CoV-2 S-protein binds to ACE2 with much higher affinity and stability than that of SARS-CoVs. Molecular interactions between ACE2-S and TMPRSS2-S are crucial and preciously mediated by specific residues. Structural stability, binding affinity and level of expression of these three interacting proteins are key susceptibility factors for COVID-19. Specific protein�protein interactions (PPI) are being identified that explains uniqueness of SARS-CoV-2 infection. Amino acid substitutions due to naturally occurring genetic polymorphisms potentially alter these PPIs and poses further clinical heterogeneity of COVID-19. Repurposing of several phytochemicals and approved drugs against ACE2, TMPRSS2 and S-protein have been proposed that could inhibit PPI between them. We have also identified some novel lead phytochemicals present in Azadirachta indica and Aloe barbadensis which could be utilized for further in vitro and in vivo anti-COVID-19 drug discovery. Uncovering details of ACE2-S and TMPRSS2-S interactions would further contribute to future research on COVID-19. � 2021, Indian Academy of Sciences.
Current therapeutic modalities and chemopreventive role of natural products in liver cancer: Progress and promise
(Baishideng Publishing Group Inc, 2023-01-15T00:00:00) Singh, Amit Kumar; Singh, Shiv Vardan; Kumar, Ramesh; Kumar, Shashank; Senapati, Sabyasachi; Pandey, Abhay K
Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year, with an estimated 5-year survival rate of 30%�35% after diagnosis. Hepatocellular carcinoma (HCC) constitutes a significant subtype of liver cancer (approximate75%) and is considered primary liver cancer. Treatment for liver cancer mainly depends on the stage of its progression, where surgery including, hepatectomy and liver transplantation, and ablation and radiotherapy are the prime choice. For advanced liver cancer, various drugs and immunotherapy are used as first-line treatment, whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins. Sorafenib and lenvatinib are first-line therapies, while regorafenib and ramucirumab are secondline therapy. Various metabolic and signaling pathways such as Notch, JAK/ STAT, Hippo, TGF-?, and Wnt have played a critical role during HCC progression. Dysbiosis has also been implicated in liver cancer. Drug-induced toxicity is a key obstacle in the treatment of liver cancer, necessitating the development of effective and safe medications, with natural compounds such as resveratrol, curcumin, diallyl sulfide, and others emerging as promising anticancer agents. This review highlights the current status of liver cancer research, signaling pathways, therapeutic targets, current treatment strategies and the chemopreventive role of various natural products in managing liver cancer � The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved
A duodenal mucosa transcriptome study identified reduced expression of a novel gene CDH18 in celiac disease
(Elsevier B.V., 2023-10-09T00:00:00) Banerjee, Pratibha; Sood, Ajit; Midha, Vandhana; Narang, Vikram; Grover, Jasmine; Senapati, Sabyasachi
Background: Celiac disease (CD) a complex immune disease that affects duodenal mucosa. Identification of tissue specific biomarkers is expected to improve the existing biopsy based CD diagnosis. Aims: To investigate the differentially expressed genes (DEGs) in duodenal mucosa tissue to identify clinically relevant gene expression pattern in CD. Methods: Whole RNA extracted from the duodenal biopsies of three CD patients and four non-CD controls were sequenced. Significant DEGs were identified. Prioritized DEGs were validated using qRT-PCR in an independent group (CD=23; Control=26). Enriched pathways were analyzed, protein-protein interaction networks were evaluated. Results: 923 DEGs comprising of 135 up-regulated, and 788 down-regulated genes, with p-value?0.05; log2FC>2 or <-2 were identified. A novel down-regulated gene CDH18 (p = 0.03; log2FC=?0.74) was identified. Previously known CXCL9 was replicated. CDH18, a trans-membrane protein was found to interact with other CDH proteins, ?/? catenins, and other membrane transporters such as SLC and ABCB. Pathways and protein networks contributing in channel activity (p = 2.15E-12), membrane transporters (p = 2.15E-12), and cellular adhesion (p = 8.05E-6) were identified. Conclusions: CDH18, a novel DEG identified in the present study is a pivotal gene involved in maintaining epithelial membrane organization and integrity. The functional significance of lower expression of CDH18 in pathogenesis of CD warranted to be investigated. CDH18 expression could be tested for its effectiveness in diagnostic, prognostic and therapeutic purposes. � 2023 Editrice Gastroenterologica Italiana S.r.l.
Epidemiology and genetics of granulomatosis with polyangiitis
(Springer Science and Business Media Deutschland GmbH, 2021-10-11T00:00:00) Banerjee, Pratibha; Jain, Arushi; Kumar, Uma; Senapati, Sabyasachi
Granulomatosis with polyangiitis (GPA) previously known as Wegener�s granulomatosis (WG)�is a rare rheumatic disease affecting subjects of all ages. Prevalence and incidence of this systemic disease greatly varies across different ethnic groups. GPA is the commonest form of ANCA-associated vasculitis (AAV) with PR3 positivity among 85�95% of the cases. Scientific investigations of GPA is warranted because�its severity, clinical heterogeneity, fast disease manifestation and end-organ damage. The etiology of GPA is still unknown. Major role of HLA and non-HLA genes with immune functions were identified, however, very limited replication was observed in different ethnic populations. In the present review, we have discussed the updates on the global epidemiology and contribution of HLA and major non-HLA genes/loci in GPA. We have also highlighted the cross disease association of GPA associated genes that may help in better disease management and predictive medicine. We proposed that high-resolution HLA typing and development of genetic risk model would help in early disease diagnosis and understanding the prognosis. � 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Evaluation Of Association Of Folic Acid Metabolism In Chronic Obstructive Pulmonary Disease
(Central University of Punjab, 2018) Chaudhary, Deepti; Senapati, Sabyasachi
COPD is characterized by increasing breathlessness. It is the fourth cause of death in the world and it is currently presenting a major global public health challenge, causing premature death from pathophysiological complications. It continues to be an important cause of morbidity, mortality, and health-care costs worldwide. It is a global health issue, with cigarette smoking being an important risk factor universally with several other factors, such as exposure to indoor and outdoor air pollution, occupational hazards, and infections. As the global population ages, the burden of COPD will increase in years to come. Folic acid or vitamin B9 is a water soluble vitamin plays a major role in metabolism. Since, COPD is a disease characterized by complex nutritional abnormalities and lower level of vitamin B9 and B12. Homocysteine or total homocysteine is a sulfur containing amino acid, acts as an intermediate in the metabolism of methionine in the folic acid or folate pathway. As observed among general population hyperhomocysteinaemia (mild to moderate), is mainly associated with vitamin B deficiencies, which are considered to be essential cofactors for the level and catabolism of hcy. Assessment of level of micronutrients is useful in establishing effects in COPD.
FTIR based approach to study EnaC mechanosensory functions
(Elsevier Ltd, 2021-07-19T00:00:00) Govindan, Rekha; Banerjee, Pratibha; Dhania, Narender K.; Senapati, Sabyasachi
The pulmonary epithelial sodium ion channel (ENaC) is gaining importance for its sodium gating and mechanosensitive roles. The mechano functional studies on ENaC suggest direct molecular interactions between the ENaC protein with cytoskeleton microtubules and other extracellular matrix components. Also, in few mechanotransduction studies, ENaC was shown to respond both to membrane stretch as well as cell volume changes. However, the conformational characteristic of ENaC during sodium and mechano gating are yet to be fully elucidated. Thus obtaining ENaC protein conformational spectrum based on Fourier Transform Infrared Radiation (FTIR) spectroscopy in solution will be useful in predicting the nature of conformational changes occurring during any cell volume changes in an epithelial cell. The conformational spectrum looks promising in studying the disease biology of cystic fibrosis (CF) and CF like conditions that arise due to abnormal ion conductance membrane proteins and subsequent frequent fluid retentions. This review article presents the basics of epithelial ENaC protein as a gated mechanosensor and FTIR for developing fluid dynamics of ENaC protein. This can be applied to develop an ENaC based quantum mechanosensor for the prognosis as well as diagnosis of cystic fibrosis (CF) and allied lung diseases. � 2021 Elsevier Ltd
Functional implications of the CpG island methylation in the pathogenesis of celiac disease
(Springer Science and Business Media B.V., 2022-05-28T00:00:00) Ghosh, Souparni; Khetarpal, Preeti; Senapati, Sabyasachi
Investigation of gene-environment cross talk through epigenetic modifications led to better understanding of the number of complex diseases. Clinical heterogeneity and differential treatment response often contributed by the epigenetic signatures which could be personal. DNA methylation at CpG islands presents a critical nuclear process as a result of�gene-environment interactions. These CpG islands are frequently present near the promoter sequence of genes and get differentially methylated under specific environmental conditions. Technical advancements facilitate in high throughput screening of differentially methylated CpG islands. Recent epigenetic studies unraveled several CD susceptibility genes expressed in peripheral blood lymphocytes�(PBLs), duodenal mucosa, lamina and epithelial cells that are influenced by differentially methylated CpG islands. Here we highlighted these susceptibility genes; classify these genes based on cellular functions and tissue of expression. We further discussed how these genes interacts with each other to influence critical pathways like NF-?B signaling pathway, IL-17 signaling cascade, RIG-I like receptor signaling pathway, NOD-like receptor pathways among several others. This review also shed light on how gut microbiota may lead to the differential methylation of CpG islands of CD susceptibility genes. Large scale epigenetic studies followed by estimation of heritability of these CpG methylation and polygenic risk score estimation of these genes would prioritize potentially druggable targets for better therapeutics. In vivo studies are warranted to unravel further cellular responses to CpG methylation. � 2022, The Author(s), under exclusive licence to Springer Nature B.V.
Genetic Variants of Steroidogenesis and Gonadotropin Pathways and Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-analysis
(Mary Ann Liebert Inc., 2023-10-25T00:00:00) Sharma, Priya; Singh, Abhilash Kumar; Senapati, Sabyasachi; Kapoor, Harmanpreet Singh; Goyal, Lajya Devi; Kaur, Balpreet; Kamra, Pooja; Khetarpal, Preeti
Genetic variants are predisposing factors to polycystic ovary syndrome (PCOS), a multifactorial condition that often gets triggered due to various environmental factors. The study investigates the association of the variants of genes that are involved in the steroidogenesis pathway or gonadotropin pathway with the risk of PCOS. Appropriate keywords for predetermined genes were used to search in PubMed, Google Scholar, Science Direct, and Central Cochrane Library up to January 11, 2023. PROSPERO (CRD42022275425). Inclusion criteria: (a) case�control study; (b) genotype or allelic data. Exclusion criteria were: (a) duplicate studies; (b) clinical trials, systematic reviews, meta-analysis or conference abstract, case reports; (c) other than the English language; (d) having insufficient data; e) genetic variants for which meta-analysis has been reported recently and does not have a scope of the update. Various genetic models were applied as per data availability. Overall 12 variants of 7 genes were selected for the analysis. Relevant data were extracted from 47 studies which include 10,584 PCOS subjects and 16,150 healthy controls. Meta-analysis indicates a significant association between TOX3 rs4784165 [ORs = 1.08, 95% CI (1.00�1.16)], HMGA2 rs2272046 [ORs = 2.73, 95% CI (1.97�3.78)], YAP1 rs1894116 [OR = 1.22, 95% CI (1.13�1.33)] and increased risk of PCOS. Whereas FSHR rs2268361 [ORs = 0.84, 95% CI (0.78�0.89)] is associated with decreased PCOS risk. When sensitivity analysis was carried out, the association became significant for CYP19 rs700519 and FSHR rs6165 under an additive model. In addition, C9Orf3 rs3802457 became significantly associated with decreased PCOS risk with the removal of one study. Insignificant association was observed for CYP19A (rs2470152), FSHR (rs2349415, rs6166), C9Orf3 (rs4385527), GnRH1 (rs6185) and risk of PCOS. Our findings suggest association of CYP19A (rs700519), TOX3 (rs4784165), HMGA2 (rs2272046), FSHR (rs6165, rs2268361), C9orf3 (rs3802457), and YAP1 (rs1894116) with risk for PCOS. � Mary Ann Liebert, Inc.
Identification of potential natural inhibitors of SARS-CoV2 main protease by molecular docking and simulation studies
(Taylor and Francis Ltd., 2020-06-01T00:00:00) Gupta, Sanjay; Singh, Atul Kumar; Kushwaha, Prem Prakash; Prajapati, Kumari Sunita; Shuaib, Mohd; Senapati, Sabyasachi; Kumar, Shashank
Coronaviruses are contagious pathogens primarily responsible for respiratory and intestinal infections. Research efforts to develop antiviral agents against coronavirus demonstrated the main protease (Mpro) protein may represent effective drug target. X-ray crystallographic structure of the SARS-CoV2 Mpro protein demonstrated the significance of Glu166, Cys141, and His41 residues involved in protein dimerization and its catalytic function. We performed in silico screening of compounds from Curcuma longa L. (Zingiberaceae family) against Mpro protein inhibition. Employing a combination of molecular docking, scoring functions, and molecular dynamics simulations, 267 compounds were screened by docking on Mpro crystallographic structure. Docking score and interaction profile analysis exhibited strong binding on the Mpro catalytic domain with compounds C1 (1E,6E)-1,2,6,7-tetrahydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione) and C2 (4Z,6E)?1,5?dihydroxy?1,7?bis(4?hydroxyphenyl)hepta?4,6?dien?3?one as lead agents. Compound C1 and C2 showed minimum binding score (�9.08 and �8.07 kcal/mole) against Mpro protein in comparison to shikonin and lopinavir (? ?5.4 kcal/mole) a standard Mpro inhibitor. Furthermore, principal component analysis, free energy landscape and protein-ligand energy calculation studies revealed that these two compounds strongly bind to the catalytic core of the Mpro protein with higher efficacy than lopinavir, a standard antiretroviral of the protease inhibitor class. Taken together, this structure based optimization has provided lead on two natural Mpro inhibitors for further testing and development as therapeutics against human coronavirus. Communicated by Ramaswamy H. Sarma. � 2020 Informa UK Limited, trading as Taylor & Francis Group.
Implications of vitamin D deficiency in systemic inflammation and cardiovascular health
(Taylor and Francis Ltd., 2023-06-24T00:00:00) Dey, Sanjay Kumar; Kumar, Shashank; Rani, Diksha; Maurya, Shashank Kumar; Banerjee, Pratibha; Verma, Madhur; Senapati, Sabyasachi
Clinical, epidemiological, and molecular studies have sufficiently highlighted the vitality of vitamin D [25(OH)D and 1,25(OH)2D] in human health and wellbeing. Globally, vitamin D deficiency (VDD) has become a public health concern among all age groups. There is a very high prevalence of VDD per the estimates from several epidemiological studies on different ethnic populations. But, population-specific scales do not support these estimates to define VDD clinically and consistent genetic associations. However, clinical studies have shown the relevance of serum vitamin D screening and oral supplementation in improving health conditions, pointing toward a more prominent role of vitamin D in health and wellness. Routinely, the serum concentration of vitamin D is measured to determine the deficiency and is correlated with physiological conditions and clinical symptoms. Recent research points toward a more inclusive role of vitamin D in different disease pathologies and is not just limited to otherwise bone health and overall growth. VDD contributes to the natural history of systemic ailments, including cardiovascular and systemic immune diseases. Considering its significant impact on premature morbidity and mortality, there is a compelling need to comprehensively review and document the direct and indirect implications of VDD in immune system deregulation, systemic inflammatory conditions, and cardio-metabolism. The recommendations from this review call for furthering our research concerning vitamin D and its direct and indirect implications. � 2023 Taylor & Francis Group, LLC.
Meta-analysis and estimation of gene expression to establish the role of SFTPD in COPD
(Central University of Punjab, 2018) Nandy, Debparna; Senapati, Sabyasachi
COPD is considered to be third leading cause of death by 2020. So far, there is no proper biomarker available for the diagnosis of all the different sub-phenotypes. Multiple GWAS studies have reported the role of SFTPD (both genetic and serum protein) as a diagnosis biomarker. This current study aims to systemic - review and meta-analyse the association of anthropometric parameter (Smoking status, gender), Protein biomarker (serum SFTPD) and genetic biomarker (SFTPD rs721917) with COPD and its other phenotypes. To support the secondary findings, this study also aims to analyse the expression of SFTPD gene among COPD cases and healthy control from North Indian population. So far bronchodilators therapy are available for providing temporary relief to the patients. But bronchodilators are found to be associated with multiple number of side-effects. Indian Traditional medicine options like Ayurveda and yoga has lot to offer in this case. Many local Indian herbs are found to be significantly effective against COPD condition. Most importantly this herbs don't have any side effects. Pranayama and Dhyana have also been found to be improving Lung functions in multiple studies.
Meta-analysis confirmed genetic susceptibility conferred by multiple risk variants from CTLA4 and SERPINA1 in granulomatosis with polyangiitis
(John Wiley and Sons Inc, 2022-06-03T00:00:00) Banerjee, Pratibha; Kumar, Uma; Khetarpal, Preeti; Senapati, Sabyasachi
Background: Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease. Smaller sample size and complex nature of the disease pathogenesis has made it challenging to perform well-powered genetic investigations. We performed a systematic review based meta-analysis in GPA to investigate the genetic susceptibility conferred by non-human leukocyte antigen (non-HLA) candidate genes. Methods: A systematic review was performed using web-based literature search and eligible studies were included following inclusion-exclusion criteria. Studies were evaluated for their quality of evidence and study outcome was assessed using the Newcastle-Ottawa Scale and Grades of Research, Assessment, Development and Evaluation tools. Reviewer's agreement was accessed through Cohen's ? value. Meta-analyses were performed using RevMan 5 tool. Meta-odds ratio (meta-OR) and Z test P value were evaluated to estimate the genetic susceptibility for each of the variants. Results: Eighteen studies were found eligible and 7 genetic variants from only 4 genes, namely CTLA4, PRTN3, SERPINA1 and PTPN22 could be studied for meta-analysis. rs231775-G (49-G) (Meta-OR�=�1.42 [1.14-1.76]; P�=.001) of CTLA4 and rs7151526-A (Meta-OR�=�2.70 [1.51-4.85]; P�=.0008) of SERPINA1 were confirmed to be predisposing alleles, and rs5742909-C (318-C) (Meta-OR�=�0.65 [0.44-0.97]; P�=.03) of CTLA4 was found to be protective for GPA. In concordance with the genetic association of rs7151526-A, serological marker for the same variant �Z� allele of SERPINA1 was found to be predisposing (Meta-OR�=�12.60 [5.01-31.68]; P <.00001) for GPA. Conclusion: Genetic variants confirmed in this study play critical roles in T-cell mediated immune function and could be significantly implicated in GPA. Molecular pathology studies are warranted to confirm their role. These markers could be used for efficient patient classification and disease management. � 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.
A meta-analysis suggests the association of reduced serum level of vitamin D and T-allele of Fok1 (rs2228570) polymorphism in the vitamin D receptor gene with celiac disease
(Frontiers Media S.A., 2023-01-19T00:00:00) Shree, Tanya; Banerjee, Pratibha; Senapati, Sabyasachi
Purpose: As an immune-modulator, vitamin D is known to regulate immune response and is implicated in disease pathogenesis. Celiac disease (CD) is a systemic autoimmune disease and susceptibility conferred by vitamin D metabolism is under investigation. Studies on the association of vitamin D metabolism and genetic polymorphisms are expected to explain CD pathogenesis. We performed a systematic review�based meta-analysis to investigate the 25(OH)D serum levels and susceptibility conferred by the genetic variants of VDR in CD. Methods: Systematic review was conducted through a web-based literature search following stringent study inclusion�exclusion criteria. The Newcastle�Ottawa Scale and GRADE tools were used to assess the quality of evidence in studies and the study outcome. Cohen's ? value was estimated to access the reviewer's agreement. RevMan 5.4.1 was used to perform the meta-analyses. Weighted mean difference and Meta p-value was assessed for 25(OH)D serum levels. Meta-odds ratio and Z-test p-value were evaluated to estimate the allelic susceptibility of VDR variants. Results: A total of 8 out of 12 studies were evaluated for �25(OH)D� serum level, while four studies were found eligible for SNPs (Bsm1, Apa1, Fok1, and Taq1) of VDR. Significantly higher levels [WMD = 5.49, p < 0.00001] of 25(OH)D were observed in healthy controls than in patients with CD. rs2228570-T (Fok1) [Meta-OR = 1.52, p = 0.02] was confirmed to be predisposing allele for CD. Conclusion: Reduced serum level of 25(OH)D and association of Fok1 T-allele of VDR confirmed in this study plays a critical role in immunomodulation and maintaining barrier integrity, which is majorly implicated in CD. Copyright � 2023 Shree, Banerjee and Senapati.
Microglia Specific Drug Targeting Using Natural Products for the Regulation of Redox Imbalance in Neurodegeneration
(Frontiers Media S.A., 2021-04-13T00:00:00) Maurya, Shashank Kumar; Bhattacharya, Neetu; Mishra, Suman; Bhattacharya, Amit; Banerjee, Pratibha; Senapati, Sabyasachi; Mishra, Rajnikant
Microglia, a type of innate immune cell of the brain, regulates neurogenesis, immunological surveillance, redox imbalance, cognitive and behavioral changes under normal and pathological conditions like Alzheimer�s, Parkinson�s, Multiple sclerosis and traumatic brain injury. Microglia produces a wide variety of cytokines to maintain homeostasis. It also participates in synaptic pruning and regulation of neurons overproduction by phagocytosis of neural precursor cells. The phenotypes of microglia are regulated by the local microenvironment of neurons and astrocytes via interaction with both soluble and membrane-bound mediators. In case of neuron degeneration as observed in acute or chronic neurodegenerative diseases, microglia gets released from the inhibitory effect of neurons and astrocytes, showing activated phenotype either of its dual function. Microglia shows neuroprotective effect by secreting growths factors to heal neurons and clears cell debris through phagocytosis in case of a moderate stimulus. But the same microglia starts releasing pro-inflammatory cytokines like TNF-?, IFN-?, reactive oxygen species (ROS), and nitric oxide (NO), increasing neuroinflammation and redox imbalance in the brain under chronic signals. Therefore, pharmacological targeting of microglia would be a promising strategy in the regulation of neuroinflammation, redox imbalance and oxidative stress in neurodegenerative diseases. Some studies present potentials of natural products like curcumin, resveratrol, cannabidiol, ginsenosides, flavonoids and sulforaphane to suppress activation of microglia. These natural products have also been proposed as effective therapeutics to regulate the progression of neurodegenerative diseases. The present review article intends to explain the molecular mechanisms and functions of microglia and molecular dynamics of microglia specific genes and proteins like Iba1 and Tmem119 in neurodegeneration. The possible interventions by curcumin, resveratrol, cannabidiol, ginsenosides, flavonoids and sulforaphane on microglia specific protein Iba1 suggest possibility of natural products mediated regulation of microglia phenotypes and its functions to control redox imbalance and neuroinflammation in management of Alzheimer�s, Parkinson�s and Multiple Sclerosis for microglia-mediated therapeutics. � Copyright � 2021 Maurya, Bhattacharya, Mishra, Bhattacharya, Banerjee, Senapati and Mishra.
mTOR and AMP-Activated Protein Kinase in Obesity and Cancer
(Springer Singapore, 2021-07-18T00:00:00) Biswas, Indranil; Maurya, Shashank Kumar; Senapati, Sabyasachi
The mTOR (mechanistic target of rapamycin) is the main regulator of important cellular processes, including cellular growth, proliferation, protein synthesis, protein remodeling, autophagy, and cell metabolism in response to nutrition status, growth factor, and stress signals. Previous studies demonstrated that mTOR signaling plays a crucial role in the function of adipose tissue such as adipogenesis, lipid metabolism, thermogenesis, and adipokine biosynthesis and release. Nutritional status in adipose tissues is different than its surrounding microenvironment, which receive altered metabolic ques. from the adipose tissues. In regard to its critical role in cellular processes, it is expected that obesity and related metabolic disorders will have direct role in dysregulation of mTOR signaling. Aberrant mTOR signaling is commonly observed in different types of cancer. Hyperactivation of mTORC1 pathway activates cell proliferation and decreased autophagy, which leads to initiation of tumor growth, progression, and angiogenesis. Another regulator of metabolic activity, adenosine monophosphate (AMP)-activated protein kinase (AMPK), maintains the energy homeostasis in response to metabolic alteration. Previous research demonstrated that AMPK is a key cellular energy sensor responsible for regulating the metabolic activity of brown and beige adipose tissues. AMPK has also been demonstrated to negatively regulate diabetes, cardiovascular disease, and other metabolic syndromes. Apart from metabolic syndrome and diabetes, the AMPK signaling has shown therapeutic potential due to its unique potential in regulating of cancer cell proliferation via cell metabolism reprogramming.. Previous reports suggest the tumor suppressive role of AMPK that sense the energy deficiency in solid tumors, thereby inhibit the cellular proliferation. However, recent data proposes that tumor cells gain growth advantage in oxygen and nutrient deprived condition via exploiting AMPK activation. In light of adipose tissue associated tumors, it is well known that adipose tissues activate inflammation in response oxygen deprivation. However, the role of altered metabolism, specifically interaction between adipose tissues and tumor microenvironment, in terms of mTOR and AMPK signaling is not well known. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Taylor and Francis Pte Ltd. 2021.
Multiple allelic associations from genes involved in energy metabolism were identified in celiac disease
(Springer, 2021-06-23T00:00:00) Bhagavatula, Sandilya; Banerjee, Pratibha; Sood, Ajit; Midha, Vandana; Thelma, B.K.; Senapati, Sabyasachi
Energy metabolism is a critical factor that influences disease pathogenesis. Recent high-throughput genomic studies have enabled us to look into disease biology with greater details. Celiac disease (CD) is an inflammatory autoimmune disease where ~60 non-HLA genes were identified which in conjunction with HLA genes explain ~55% of the disease heritability. In this study we aimed to identify susceptibility energy metabolism genes and investigate their role in CD. We re-analysed published Immunochip genotyping data, which were originally analysed for CD association studies in north Indian and Dutch population. 269 energy metabolism genes were tested. Meta-analysis was done for the identified SNPs. To validate the functional implications of identified markers and/or genes, in silico functional annotation was performed. Six SNPs were identified in north Indians, of which three markers from two loci were replicated in Dutch. rs2071592 (PMeta=5.01e?75) and rs2251824 (PMeta=1.87e?14) from ATP6V1G2-NFKBIL1-DDX39B locus and rs4947331 (PMeta= 9.85e?13) from NEU1 locus were found significantly associated. Identified genes are key regulators of cellular energy metabolism and associated with several immune mediated diseases. In silico functional annotation showed significant biological relevance of these novel markers and genes. FDI approved therapeutics against ATP6V1G2 and NEU1 are currently in use to treat chronic and inflammatory diseases. This study identified two pathogenic loci, originally involved in energy metabolism. Extensive investigation showed their synergistic role in CD pathogenesis by promoting immune mediated enteric inflammation. Proposed CD pathogenesis model in this study needs to be tested through tissue-on-chip and in vivo methods to ensure its translational application. � 2021, Indian Academy of Sciences.
Obesity-Induced Chronic Low-Level Inflammation and Cancers
(Springer Singapore, 2021-07-18T00:00:00) Bhattacharya, Neetu; Maurya, Shashank Kumar; Bhattacharya, Amit; Senapati, Sabyasachi
The World Health Organization (WHO) has highlighted �overweight and obesity� as a public health concern and a significant risk factor for several chronic diseases, including diabetes, cardiovascular diseases, and cancers. The association between the different factors that can lead to the chronic inflammatory condition in the obese persons and their effect in tumorigenesis and several cancers (esophageal, liver, colon, postmenopausal breast, and endometrial cancers) have been partially unraveled. The functional association between inflammation and cancer is not new. Existing hypotheses of obesity-associated cancer underline direct effects of dietary ingredients or metabolic imbalance in the body. The recent evidences suggest a significant connection between chronic inflammation and cancer risk, possibly involving dietary and metabolic components. In the nineteenth century, Virchow first addressed the involvement of immune cells in tumorigenesis (Balkwill and Mantovani, The Lancet 357:539�545, 2001). The mediators and cellular effectors of inflammation are essential components of the tumor microenvironment and are more likely to contribute to tumor growth, its development and immunosuppression (Coussens and Werb, Nature 420:860�867, 2002). A strong relationship of chronic inflammation with malignant diseases can be traced in several individuals with inflammatory bowel diseases, such as Ulcerative colitis and Crohn�s disease, also developing colon carcinogenesis. Further, hepatitis C infection in the hepatic cells has been predisposed to liver carcinoma. Understanding these molecular pathways of cancer-related inflammation could lead to identification of new target molecules for improved diagnosis and treatment regimes. In this chapter, we will critically discuss the roles of cytokines, chemokines, growth factors, and inflammatory signaling pathways related to obesity and cancer risk. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Taylor and Francis Pte Ltd. 2021.