Publications by authors named "Prithvi Singh"

41 Publications

Comprehensive Integrative Analysis Reveals the Association of with Macrophage Infiltration and Polarization in Lung Cancer Microenvironment.

Cells 2021 Aug 14;10(8). Epub 2021 Aug 14.

Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India.

Macrophage polarization and infiltration to the tumor microenvironment (TME) is a critical determining factor for tumor progression. Macrophages are polarized into two states-M1 (pro-inflammatory, anti-tumorigenic and stimulated by LPS or ) and M2 (anti-inflammatory pro-tumorigenic and stimulated by ) phenotypes. Specifically, M2 macrophages enhance tumor cell growth and survival. Recent evidences suggest the pivotal role of microRNAs in macrophage polarization during the development of Non-small cell lung cancer (NSCLC), thus proposing a new therapeutic option to target lung cancer. In silico analysis determined cogent upregulation of , downregulation of and miR-34a-5p in NSCLC tissues, consequently worsening the overall survival of NSCLC patients. We observed a significant association of with macrophage infiltration and polarization in NSCLC. We found that is critically implicated in M2 polarization of macrophages, which, in turn, promotes tumorigenesis. expression correlated with miR-34a-5p and in a feed-forward loop (FFL), both of which are implicated in immune regulation. Mechanistic overexpression of miR-34a-5p in macrophages ( stimulated) inhibits , along with downregulation of , (M2 macrophage specific markers), and upregulation of , , (M1 macrophage specific markers), demonstrating macrophage polarization switch from M2 to M1 phenotype. Moreover, co-culture of these macrophages with NSCLC cells reduces their proliferation, wound healing, clonogenic capacity and enhanced NO-mediated apoptosis. Further, transfection of miR-34a-5p in NSCLC cells, also degrades , but enhances the expression of regulated genes-, (pro-inflammatory mediators), which is further enhanced upon co-culture with stimulated macrophages. Additionally, we observed a significant increase in /NO content upon co-culture, suggesting polarization reversion of macrophages from M2 to M1, and eventually leading to anti-tumor effects. Our findings thus show a significant role of in tumorigenesis and TAM polarization of NSCLC. However, miR-34a-5p mediated targeting of these molecular networks will provide a better therapeutic intervention for NSCLC.
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http://dx.doi.org/10.3390/cells10082091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392240PMC
August 2021

Survival-Based Biomarker Module Identification Associated with Oral Squamous Cell Carcinoma (OSCC).

Biology (Basel) 2021 Aug 8;10(8). Epub 2021 Aug 8.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.

Head and neck squamous cell carcinoma (HNSC) is one of the most common malignant tumors worldwide with a high rate of morbidity and mortality, with 90% of predilections occurring for oral squamous cell carcinoma (OSCC). Cancers of the mouth account for 40% of head and neck cancers, including squamous cell carcinomas of the tongue, floor of the mouth, buccal mucosa, lips, hard and soft palate, and gingival. OSCC is the most devastating and commonly occurring oral malignancy, with a mortality rate of 500,000 deaths per year. This has imposed a strong necessity to discover driver genes responsible for its progression and malignancy. In the present study we filtered oral squamous cell carcinoma tissue samples from TCGA-HNSC cohort, which we followed by constructing a weighted PPI network based on the survival of patients and the expression profiles of samples collected from them. We found a total of 46 modules, with 18 modules having more than five edges. The KM and ME analyses revealed a single module (with 12 genes) as significant in the training and test datasets. The genes from this significant module were subjected to pathway enrichment analysis for identification of significant pathways and involved genes. Finally, the overlapping genes between gene sets ranked on the basis of weighted PPI module centralities (i.e., degree and eigenvector), significant pathway genes, and DEGs from a microarray OSCC dataset were considered as OSCC-specific hub genes. These hub genes were clinically validated using the IHC images available from the Human Protein Atlas (HPA) database.
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http://dx.doi.org/10.3390/biology10080760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389591PMC
August 2021

Tinospora cordifolia activates PPARγ pathway and mitigates glomerular and tubular cell injury in diabetic kidney disease.

Phytomedicine 2021 Jul 16;91:153663. Epub 2021 Jul 16.

Pharmacology and Toxicology Laboratory, Dietetics and Nutrition Technology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur-176061, H.P., India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, U.P. -201002, India. Electronic address:

Background: Diabetic Kidney Disease (DKD) is a common complication of diabetes and a leading cause of end-stage renal disease progression. Therefore, therapeutic strategies are desirable to mitigate the progression of disease into more severe consequences. Hypothesis/Purpose:Tinospora cordifolia is a traditionally known antidiabetic plant; however, its effect against DKD remains unexplored. Therefore, in the present study, we assessed the efficacy and mechanism of action of Tinospora cordifolia extract (TC) against DKD.

Methods: The molecular interaction of the various phytoconstituents of TC with PPARγ were analyzed in silico. The effect of TC was studied on the viability, cell cycle, and gene expressions (PPARγ, TGFβ, and αSMA) in high glucose treated NRK-52E and SV40 MES13 cells. Further, streptozotocin-induced diabetic rats were treated with TC for eight weeks, and the effects on different biochemical, histological and molecular parameters were studied.

Results: In silico analysis revealed the integration of various phytoconstituents of TC with PPARγ. It further increased PPARγ and decreased TGFβ and αSMA expressions in NRK-52E and SV40 MES13 cells. In diabetic rats, TC improved the fasting blood glucose, serum urea, and creatinine levels. It also lowered the urine microalbumin and advanced glycation end products (AGEs) levels. Histopathological studies revealed the preventive effect of TC on degenerative changes, mesangial proliferation and glomerular hypertrophy. Further, it reduced the inflammation and fibrotic changes in the kidney tissue estimated by various markers. The kidney tissue and gene expression analysis revealed the augmented levels of PPARγ after TC treatment.

Conclusion: In conclusion, TC exerted the protective effect against DKD by inhibiting inflammation and fibrogenesis through the activation of PPARγ dependent pathways.
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http://dx.doi.org/10.1016/j.phymed.2021.153663DOI Listing
July 2021

Revealing new therapeutic opportunities in hypertension through network-driven integrative genetic analysis and drug target prediction approach.

Gene 2021 Oct 19;801:145856. Epub 2021 Jul 19.

Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India. Electronic address:

Epidemiological studies have established that untreated hypertension (HTN) is a major independent risk factor for developing cardiovascular diseases (CVD), stroke, renal failure, and other conditions. Several important studies have been published to prevent and manage HTN; however, antihypertensive agents' optimal choice remains controversial. Therefore, the present study is undertaken to update our knowledge in the primary treatment of HTN, specifically in the setting of other three important diseases. MicroRNAs (miRNAs) are remarkably stable short endogenous conserved non-coding RNAs that bind to the mRNA at its (3' UTR) to regulate its gene expression by causing translational repression or mRNA degradation. Through their coordinated activities on different pathways and networks, individual miRNAs control normal and pathological cellular processes. Therefore, to identify the critical miRNA-mRNA-TF interactions, we performed systematic bioinformatics analysis. We have also employed the molecular modelling and docking approach to identify the therapeutic target that delivers novel empathies into Food and Drug Administration approved and herbal drug response physiology. Gene Expression Omnibus (GEO) was employed to identify the differentially expressed genes (DEGs) and hub genes- KNG1, HLA-DPB1, CXCL8, IL1B, and BCL2. The HTN associated feed-forward loop (FFL) network included miR-9-5p, KNG1 and AR. We employed high throughput screening to get the best interacting compounds, telmisartan and limonin, that provided a significant docking score (-13.3 and -12.0 kcal/mol) and a potential protective effect that may help to combat the impact of HTN. The present study provides novel insight into HTN etiology through the identification of mRNAs and miRNAs and associated pathways.
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http://dx.doi.org/10.1016/j.gene.2021.145856DOI Listing
October 2021

Steroidal saponins from Trillium govanianum as α-amylase, α-glucosidase, and dipeptidyl peptidase IV inhibitory agents.

J Pharm Pharmacol 2021 Mar;73(4):487-495

Chemical Technology Division, CSIR-IHBT, Palampur, India.

Objective: To provide the scientific basis for the utility of rhizome of Trillium govanianum as nutraceutical supplements in managing physiological glycemic levels.

Methods: The in vitro enzyme inhibitory activity of the extract, fractions, and the isolated steroidal saponins from the rhizome part of T. govanianum was carried out against α-amylase, α-glucosidase, and dipeptidyl peptidase IV. The molecular interactions, binding score, and pharmacokinetic parameters (absorption, distribution metabolism, and excretion) of steroidal saponins were analyzed by the Schrodinger molecular docking software.

Key Findings: Current study explained that the extract, fractions, and isolated steroidal saponins from T. govanianum possess good α-amylase and α-glucosidase inhibitory activity while moderate dipeptidyl peptidase IV inhibitory activity. Moreover, in vitro results revealed that borassoside E (IC50 7.15 ± 1.78 μM), protodioscin (IC50 6.72 ± 0.04 μM), and diosgenin (IC50 12.75 ± 2.70 μM) are most effective in inhibiting the activity of α-amylase, α-glucosidase, and dipeptidyl peptidase IV, respectively. Current in silico and in vitro studies established an association between the steroidal saponins from T. govanianum and their molecular interactions with α-amylase, α-glucosidase, and dipeptidyl peptidase IV.

Conclusion: The results of this investigation suggest that fractions and steroidal saponins from T. govanianum exhibit good antidiabetic activity which could be used as nutraceutical supplements for the management of systemic glucose level.
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http://dx.doi.org/10.1093/jpp/rgaa038DOI Listing
March 2021

Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer.

Mol Oncol 2021 May 13;15(5):1450-1465. Epub 2021 Mar 13.

Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, India.

Striking similarity exists between metabolic changes associated with embryogenesis and tumorigenesis. Chromobox proteins-CBX2/4/6/7/8, core components of canonical polycomb repressor complex 1, play essential roles in embryonic development and aberrantly expressed in breast cancer. Understanding how altered CBX expression relates to metabolic reprogramming in breast cancer may reveal vulnerabilities of therapeutic pertinence. Using transcriptomic and metabolomic data from breast cancer patients (N > 3000 combined), we performed pathway-based analysis and identified outstanding roles of CBX2 and CBX7 in positive and negative regulation of glucose metabolism, respectively. Genetic ablation experiments validated the contrasting roles of two isoforms in cancer metabolism and cell growth. Furthermore, we provide evidence for the role of mammalian target of rapamycin complex 1 signaling in mediating contrary effects of CBX2 and CBX7 on breast cancer metabolism. Underpinning the biological significance of metabolic roles, CBX2 and CBX7 were found to be the most up- and downregulated isoforms, respectively, in breast tumors compared with normal tissues. Moreover, CBX2 and CBX7 expression (not other isoforms) correlated strongly, but oppositely, with breast tumor subtype aggressiveness and the proliferation markers. Consistently, genomic data also showed higher amplification frequency of CBX2, not CBX7, in breast tumors. Highlighting the clinical significance of findings, disease-specific survival and drug sensitivity analysis revealed that CBX2 and CBX7 predicted patient outcome and sensitivity to FDA-approved/investigational drugs. In summary, this work identifies novel cross talk between CBX2/7 and breast tumor metabolism, and the results presented may have implications in strategies targeting breast cancer.
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http://dx.doi.org/10.1002/1878-0261.12894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096797PMC
May 2021

MTHFR C677T, Prothrombin G20210A, and Factor V Leiden (G1691A) Polymorphism and Beta-Thalassemia Risk: A Meta-Analysis.

Cureus 2020 Sep 30;12(9):e10743. Epub 2020 Sep 30.

Center for Advance Research, King George's Medical University, Lucknow, IND.

Background Beta (β)-thalassemia major patients frequently suffer from many vascular problems. Thrombophilia is a blood disorder that comprises imbalances in the blood coagulating factor due to ecological and hereditary components. Previous evidence shows that thrombosis is the commonest risk in beta-thalassemia patients. Several studies have examined that MTHFR C677T, prothrombin G20210A (PT G20210A), and Factor V Leiden G1691A (FVL G1691A) polymorphism play a crucial role in the development of β-thalassemia major, yet the result was questionable and uncertain. Therefore, in this study, we executed the correlation between these gene polymorphisms with β-thalassemia major patients. Methods Suitable keywords were used to search related articles in PubMed, Google Scholar, and Web of Science. In this random-effects meta-analysis, we analyzed the odds ratio (OR) for the estimation of risk. Results A total of nine research articles with 645 β-thalassemia major patients and 989 healthy controls were incorporated in this meta-analysis. The pooled OR was assessed in MTHFR C677T, PT G20210A, and FVL G1691A polymorphism. This random-effects meta-analysis demonstrated that MTHFR C677T, PT G20210A, and FVL G1691A gene polymorphism did not significantly associate with β-thalassemia major. Moreover, the heterogeneity was significantly found in genotype CC vs CT+TT C677T (I=61%) and allele C vs T (I=71%) of MTHFR and genotype GG vs GA (I=95%), GG vs GA+AA (I=95%), GA vs GG+AA (I=95%), and allele G vs A (I=93%) of FVL G1691A. Conclusion The results of this meta-analysis show that MTHFR C677T, prothrombin G20210A, and Factor V Leiden (G1691A) gene polymorphism are not a risk factor for β-thalassemia major.
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http://dx.doi.org/10.7759/cureus.10743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603879PMC
September 2020

A demographic prevalence of β Thalassemia carrier and other hemoglobinopathies in adolescent of Tharu population.

J Family Med Prim Care 2020 Aug 25;9(8):4305-4310. Epub 2020 Aug 25.

Department of Vice Chancellor, King George's Medical University, Lucknow, Uttar Pradesh, India.

Background And Aims: Hemoglobinopathies and thalassemias are the commonest single gene disorders in India. In Terai region of India, Hemoglobinopathies and thalassemias are the most common in the Tharu community. Therefore, in this study, we aim to evaluate the Hb variant analysis of hemoglobinopathies and thalassemias in a Tharu population in Lakhimpur Kheri Districts of Uttar Pradesh, India.

Materials And Methods: Total 493 individuals were recruited in this study. The demographic details and blood samples were collected from different location at Kheri district during mega health camp. Hb variant analysis was performed by high performance liquid chromatography (HPLC) system beta thalassemia short program in BIO-RAD VARIANT.

Results: Out of 493, 108 (21.9%) individual suffers with abnormal haemoglobinopathies. In which β-thalassemia trait is the commonest haemoglobinopathy (12.98%), followed by HbE trait (7.50%), and compound heterozygous HbS/β-Thalassemia trait (1.42%) in overall population. The HbF was significantly greater in HbS heterozygous (1.45 ± 1.41), whereas mean HbA2 was significantly greater in β-Thalassemia trait (5.17 ± 1.36).

Conclusion: The high incidence of hemoglobinopathies and thalassemias were observed in Tharu community in Lakhimpur Kheri districts of Uttar Pradesh, Indian.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_879_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586583PMC
August 2020

Identification of robust genes in transcriptional regulatory network of Mycobacterium tuberculosis.

IET Syst Biol 2020 10;14(5):292-296

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.

About 30% of the world population is infected with Mycobacterium tuberculosis (MTB). It is well known that the gene expression in MTB is highly variable, thus screening of traditional single-gene in MTB has been incapable to meet the desires of clinical diagnosis. In this report, the authors systemically analysed the transcription regulatory network (TRN) in MTB The complex interplay of these gene interactions has been revealed using exhaustive topological and global analysis of TRN using parameters including indegree, outdegree, degree, directed and undirected average path length (APL), and randomly performed. Results from indegree analysis reveal a set of important genes, including and which are associated with high indegree values. Gene ontology analysis suggested their importance in the virulence of MTB. In addition, APL and analysis of highly significant genes further identified some critical genes with different APL values. Among the list of genes identified, the gene has the shortest directed APL score and high outdegree value, thus suggesting their importance in maintaining network topology. This study provides a comprehensive analysis of TRN and offers a good basis of understanding for developing experimental study in search of new therapeutic targets against MTB H37Rv pathogen.
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http://dx.doi.org/10.1049/iet-syb.2020.0039DOI Listing
October 2020

Insecticidal activity of the extract, fractions, and pure steroidal saponins of Trillium govanianum Wall. ex D. Don for the control of diamondback moth (Plutella xylostella L.) and aphid (Aphis craccivora Koch).

Pest Manag Sci 2021 Feb 13;77(2):956-962. Epub 2020 Oct 13.

Entomology Laboratory, Agrotechnology Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India.

Background: Plutella xylostella L. is the major pest of crucifers globally, causing significant yield loss. Aphis craccivora Koch is the main sucking pest of legumes that transmit viral diseases, leading to economic yield reduction. To minimize loss due to pests, farmers/growers use synthetic insecticides frequently for their control, which led to insecticide resistance, detrimental to natural enemies of pest, environment, etc. Therefore, in this study, the insecticidal activity of plant extract, fractions, and pure steroidal saponins from Trillium govanianum was evaluated for their bio-efficacy against targeted pests.

Results: Parent extract was found more effective (LC = 1541.2 mg L ) against larvae of P. xylostella after 96 h than n-butanol, n-hexane, and ethyl acetate fractions (LC = 3030, 3578 and 3878.1 mg L , respectively). For A. craccivora, ethyl acetate fraction (LC = 2186.3 mg L ) was most effective after 96 h than n-hexane fraction (LC = 2234.6 mg L ), n-butanol fraction (LC = 2696.3 mg L ) and parent extract (LC = 3709.1 mg L ). Among pure molecules, govanoside B was found more effective (76% mortality, LC = 3279.5 mg L ) followed by borassoside E (74%, LC = 3467.1 mg L ) against A. craccivora after 96 h.

Conclusion: Parent extract/fractions of T. govanianum showed promising efficacy against larvae of P. xylostella and A. craccivora. Further, field study is required for its bio-efficacy against targeted pests for validation and formulation development.
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http://dx.doi.org/10.1002/ps.6107DOI Listing
February 2021

Inhibition of miRNA-34a Promotes M2 Macrophage Polarization and Improves LPS-Induced Lung Injury by Targeting Klf4.

Genes (Basel) 2020 08 20;11(9). Epub 2020 Aug 20.

Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India.

Acute respiratory distress syndrome (ARDS) is an outcome of an accelerated immune response that starts initially as a defensive measure, however, due to non-canonical signaling, it later proves to be fatal not only to the affected tissue but to the whole organ system. microRNAs are known for playing a decisive role in regulating the expression of genes involved in diverse functions such as lung development, repair, and inflammation. In-silico analyses of clinical data and microRNA databases predicted a probable interaction between miRNA-34a (miR-34a), mitogen-activated protein kinase 1 (ERK), and kruppel like factor 4 (Klf4). Parallel to in silico results, here, we show that intra-tracheal instillation of lipopolysaccharides (LPS) to mice enhanced miR-34a expression in lung macrophages. Inhibition of miR-34a significantly improved lung histology, whereas over-expression of miR-34a worsened the lung injury phenotype. miR-34a over-expression in macrophages were also demonstrated to favour pro-inflammatory M1 phenotype and inhibition of M2 polarization. In a quest to confirm this likely interaction, expression profiles of Klf4 as the putative target were analyzed in different macrophage polarizing conditions. Klf4 expression was found to be prominent in the miR-34a inhibitor-treated group but down-regulated in the miR-34a mimic treated group. Immuno-histopathological analyses of lung tissue from the mice treated with miR-34a inhibitor also showed reduced inflammatory M1 markers as well as enhanced cell proliferation. The present study indicates that miR-34a intensified LPS-induced lung injury and inflammation by regulating Klf4 and macrophage polarization, which may serve as a potential therapeutic target for acute lung injury/ARDS.
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http://dx.doi.org/10.3390/genes11090966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563942PMC
August 2020

Unravelling host-pathogen interactions: ceRNA network in SARS-CoV-2 infection (COVID-19).

Gene 2020 Dec 15;762:145057. Epub 2020 Aug 15.

Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India. Electronic address:

COVID-19 is a lurking calamitous disease caused by an unusual virus, SARS-CoV-2, causing massive deaths worldwide. Nonetheless, explicit therapeutic drugs or clinically approved vaccines are not available for COVID-19. Thus, a comprehensive research is crucially needed to decode the pathogenic tools, plausible drug targets, committed to the development of efficient therapy. Host-pathogen interactions via host cellular components is an emerging field of research in this respect. miRNAs have been established as vital players in host-virus interactions. Moreover, viruses have the capability to manoeuvre the host miRNA networks according to their own obligations. Besides protein coding mRNAs, noncoding RNAs might also be targeted in infected cells and viruses can exploit the host miRNA network via ceRNA effect. We have predicted a ceRNA network involving one miRNA (miR-124-3p), one mRNA (Ddx58), one lncRNA (Gm26917) and two circRNAs (Ppp1r10, C330019G07RiK) in SARS-CoV infected cells. We have identified 4 DEGs-Isg15, Ddx58, Oasl1, Usp18 by analyzing a mRNA GEO dataset. There is no notable induction of IFNs and IFN-induced ACE2, significant receptor responsible for S-protein binding mediated viral entry. Pathway enrichment and GO analysis conceded the enrichment of pathways associated with interferon signalling and antiviral-mechanism by IFN-stimulated genes. Further, we have identified 3 noncoding RNAs, playing as potential ceRNAs to the genes associated with immune mechanisms. This integrative analysis has identified noncoding RNAs and their plausible targets, which could effectively enhance the understanding of molecular mechanisms associated with viral infection. However, validation of these targets is further corroborated to determine their therapeutic efficacy.
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http://dx.doi.org/10.1016/j.gene.2020.145057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428439PMC
December 2020

Deciphering key genes and miRNAs associated with Hepatocellular carcinoma via network-based approach.

IEEE/ACM Trans Comput Biol Bioinform 2020 Aug 14;PP. Epub 2020 Aug 14.

Hepatocellular carcinoma (HCC) is a common type of liver cancer and has a high mortality world-widely. The diagnosis, prognoses, and therapeutics are very poor due to the unclear molecular mechanism of progression of the disease. To unveil the molecular mechanism of progression of HCC, we extract a large sample of mRNA expression levels from the GEO database where a total of 167 samples were used for study, and out of them, 115 samples were from HCC tumor tissue. This study aims to investigate the module of differentially expressed genes (DEGs) which are co-expressed only in HCC sample data but not in normal tissue samples. Thereafter, we identified the highly significant module of significant co-expressed genes and formed a PPI network for these genes. There were only six genes (namely, MSH3, DMC1, ALPP, IL10, ZNF223, and HSD17B7) obtained after analysis of the PPI network. Out of six only MSH3, DMC1, HSD17B7, and IL10 were found enriched in GO Term & Pathway enrichment analysis and these candidate genes were mainly involved in cellular process, metabolic and catalytic activity, which promote the development & progression of HCC. Lastly, the composite 3-node FFL reveals the driver miRNAs and TFs associated with our key genes.
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http://dx.doi.org/10.1109/TCBB.2020.3016781DOI Listing
August 2020

Transcriptomic analysis delineates potential signature genes and miRNAs associated with the pathogenesis of asthma.

Sci Rep 2020 08 7;10(1):13354. Epub 2020 Aug 7.

Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi, 110025, India.

Asthma is a multifarious disease affecting several million people around the world. It has a heterogeneous risk architecture inclusive of both genetic and environmental factors. This heterogeneity can be utilised to identify differentially expressed biomarkers of the disease, which may ultimately aid in the development of more localized and molecularly targeted therapies. In this respect, our study complies with meta-analysis of microarray datasets containing mRNA expression profiles of both asthmatic and control patients, to identify the critical Differentially Expressed Genes (DEGs) involved in the pathogenesis of asthma. We found a total of 30 DEGs out of which 13 were involved in the pathway and functional enrichment analysis. Moreover, 5 DEGs were identified as the hub genes by network centrality-based analysis. Most hub genes were involved in protease/antiprotease pathways. Also, 26 miRNAs and 20 TFs having an association with these hub genes were found to be intricated in a 3-node miRNA Feed-Forward Loop. Out of these, miR-34b and miR-449c were identified as the key miRNAs regulating the expression of SERPINB2 gene and SMAD4 transcription factor. Thus, our study is suggestive of certain miRNAs and unexplored pathways which may pave a way to unravel critical therapeutic targets in asthma.
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http://dx.doi.org/10.1038/s41598-020-70368-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414199PMC
August 2020

Unravelling the Role of miR-20b-5p, CCNB1, HMGA2 and E2F7 in Development and Progression of Non-Small Cell Lung Cancer (NSCLC).

Biology (Basel) 2020 Aug 1;9(8). Epub 2020 Aug 1.

Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India.

Lung cancer is a prime cause of worldwide cancer deaths, with non-small cell lung cancer (NSCLC) as a frequent subtype. Surgical resection, chemotherapy are the currently used treatment methods. Delayed detection, poor prognosis, tumor heterogeneity, and chemoresistance make them relatively ineffective. Genomic medicine is a budding aspect of cancer therapeutics, where miRNAs are impressively involved. miRNAs are short ncRNAs that bind to 3'UTR of target mRNA, causing its degradation or translational repression to regulate gene expression. This study aims to identify important miRNA-mRNA-TF interactions in NSCLC using bioinformatics analysis. GEO datasets containing mRNA expression data of NSCLC were used to determine differentially expressed genes (DEGs), and identification of hub genes-BIRC5, CCNB1, KIF11, KIF20A, and KIF4A (all functionally enriched in cell cycle). The FFL network involved, comprised of miR-20b-5p, CCNB1, HMGA2, and E2F7. KM survival analysis determines that these components may be effective prognostic biomarkers and would be a new contemplation in NSCLC therapeutics as they target cell cycle and immunosurveillance mechanisms via HMGA2 and E2F7. They provide survival advantage and evasion of host immune response (via downregulation of cytokines-IL6, IL1R1 and upregulation of chemokines-CXCL13, CXCL14) to NSCLC. The study has provided innovative targets, but further validation is needed to confirm the proposed mechanism.
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http://dx.doi.org/10.3390/biology9080201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465122PMC
August 2020

Qualitative and quantitative determination of steroidal saponins in Trillium govanianum by UHPLC-QTOF-MS/MS and UHPLC-ELSD.

Phytochem Anal 2020 Nov 3;31(6):861-873. Epub 2020 Jun 3.

Natural Product Chemistry and Process Development Division and AcSIR, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India.

Introduction: Trillium govanianum (Nag Chhatri and Teen Patra) is traditionally used for curing joint pains, wounds, and sexual disorders. Steroidal saponins are the main active components of this species. However, only a small amount of information is available about steroidal saponins of this plant.

Objective: To develop an ultra-high-performance liquid chromatography-quadrupole time of flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) and ultra-high-performance liquid chromatography-evaporative light scattering detector (UHPLC-ELSD) methods for the qualitative and quantitative determination of steroidal saponins in T. govanianum.

Method: The dried rhizomes of T. govanianum (100 mg) were extracted with ethanol-water (80:20, 10 mL) by ultrasonic treatment for 30 min at 40°C. The prepared sample was analysed by UHPLC-QTOF-MS/MS and UHPLC-ELSD for the qualitative and quantitative determination of steroidal saponins.

Result: A total of 24 saponins were identified using UHPLC-QTOF-MS/MS; seven of them were characterised by comparing with standards. Furthermore, five saponins [govanoside B (2), protodioscin (6), pennogenin tetraglycosides (11), borassoside E (21) and borassoside D (24)] were quantified using UHPLC-ELSD method in different extracts and fractions of T. govanianum. The method showed good linearity (R ≥ 0.993), limit of detection (0.92-4.09 μg/mL), limit of quantification (3.1-13.5 μg/mL), precision [intra-day relative standard deviations (RSDs) < 4.3% and inter-day RSDs < 5.5%], and accuracy (84.0-110.3%). This is the first report on the quantification of 2, 6, 11, 21 and 24 in T. govanianum.

Conclusion: The present study provides an efficient analytical method for the identification and quantification of steroidal saponins and will be helpful for the quality evaluation of T. govanianum.
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http://dx.doi.org/10.1002/pca.2951DOI Listing
November 2020

Govanoside B, a new steroidal saponin from rhizomes of .

Nat Prod Res 2020 May 6:1-9. Epub 2020 May 6.

Natural Product Chemistry and Process Development Division and AcSIR, CSIR-Institute of Himalayan Bioresource Technology, Palampur, India.

, commonly known as Nag Chhatri and Teen Patra, is a popular herbal supplement traditionally used for curing different inflammatory and sexual disorders, infection and wound healing. Steroidal saponins are considered as active components of this species. The present study demonstrated the isolation of nine steroidal saponins, including one new compound named as govanoside B () and eight known, pregna-chacotrioside (), pennogenin-triglycoside (), borassoside E (), pennogenin-tetraglycoside (), protodioscin (), clintonioside B (), pennogenin-diglycoside () and borassoside D (). This is the first report on the isolation of , , , , , and from rhizomes of . The extract, fractions and isolated compounds were further evaluated for their DPPH and ABTS radical scavenging activity.
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http://dx.doi.org/10.1080/14786419.2020.1761360DOI Listing
May 2020

Network-based identification of signature genes KLF6 and SPOCK1 associated with oral submucous fibrosis.

Mol Clin Oncol 2020 Apr 30;12(4):299-310. Epub 2020 Jan 30.

Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India.

The molecular mechanism of oral submucous fibrosis (OSF) is yet to be fully elucidated. The identification of reliable signature genes to screen patients with a high risk of OSF and to provide oral cancer surveillance is therefore required. The present study produced a filtering criterion based on network characteristics and principal component analysis, and identified the genes that were involved in OSF prognosis. Two gene expression datasets were analyzed using meta-analysis, the results of which revealed 1,176 biologically significant genes. A co-expression network was subsequently constructed and weighted gene modules were detected. The pathway and functional enrichment analyses of the present study allowed for the identification of modules 1 and 2, and their respective genes, SPARC (osteonectin), cwcv and kazal like domain proteoglycan 1 (SPOCK1) and kruppel like factor 6 (KLF6), which were involved in the occurrence of OSF. The results revealed that both genes had a prominent role in epithelial to mesenchymal transition during OSF progression. The genes identified in the present study require further exploration and validation within clinical settings to determine their roles in OSF.
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http://dx.doi.org/10.3892/mco.2020.1991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058035PMC
April 2020

Transcriptome Meta-Analysis Deciphers a Dysregulation in Immune Response-Associated Gene Signatures during Sepsis.

Genes (Basel) 2019 12 4;10(12). Epub 2019 Dec 4.

Translational Research Lab, Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, New Delhi 110025, India.

Sepsis is a life-threatening disease induced by a systemic inflammatory response, which leads to organ dysfunction and mortality. In sepsis, the host immune response is depressed and unable to cope with infection; no drug is currently available to treat this. The lungs are frequently the starting point for sepsis. This study aimed to identify potential genes for diagnostics and therapeutic purposes in sepsis by a comprehensive bioinformatics analysis. Our criteria are to unravel sepsis-associated signature genes from gene expression datasets. Differentially expressed genes (DEGs) were identified from samples of sepsis patients using a meta-analysis and then further subjected to functional enrichment and protein‒protein interaction (PPI) network analysis for examining their potential functions. Finally, the expression of the topmost upregulated genes (, , , ) was quantified by reverse transcriptase-PCR (RT-PCR), and myeloperoxidase () expression was confirmed by immunohistochemistry (IHC) staining in the lungs of a well-established sepsis mouse model. We found that all the four genes were upregulated in semiquantitative RT-PCR studies; however, showed a nonsignificant increase in expression. staining showed strong immunoreactivity in sepsis as compared to the control. This study demonstrates the role of significant and widespread immune activation (, ), along with oxidative stress () and the recruitment of neutrophils, in sepsis (, ).
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http://dx.doi.org/10.3390/genes10121005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947644PMC
December 2019

Sleep quality and insulin resistance in adolescent subjects with different circadian preference: A cross-sectional study.

J Family Med Prim Care 2019 Jul;8(7):2502-2505

Center for Advance Research (Cytogenetics Unit), King George's Medical University, Lucknow, Uttar Pradesh, India.

Background: Studies have shown that alterations in the sleep cycle can predispose to several disorders. Most of the previous studies were done on the adults. Hence, the aim of the study was to see the effect of circadian disruption on the health of adolescent population.

Materials And Methods: In this cross-sectional study, 203 subjects were enrolled. Study subjects were divided into three groups: definite evening chronotype, intermediate chronotype, and definite morning chronotype. Sleep quality was measured by Pittsburgh Sleep Quality Index (PSQI). Daytime sleepiness and chronotype were measured by Epworth Sleepiness Score and Morningness-Eveningness Questionnaire Self-Assessment version, respectively. Two hours postprandial glucose was measured after oral glucose tolerance test. Fasting blood glucose and fasting insulin were measured. Homeostasis model of assessment for insulin resistance (HOMA-IR) was calculated. Data were summarized as mean ± standard deviation. Crude odds ratios and Karl Pearson's correlation coefficient of metabolic parameters with poor sleep were calculated.

Results: Statistically significant difference was found in the mean value of poor sleep quality, 2 h postprandial blood glucose level, and insulin resistance among subjects of three groups. Subjects of evening chronotype have more significant positive correlation of 2 h postprandial blood glucose level and HOMA-IR value with poor sleep quality when compared with subjects of intermediate and morning chronotypes.

Conclusion: Subjects with evening chronotype are more prone for development of metabolic syndrome compared with subjects of intermediate and morning chronotypes if proper health policies are not adopted for adolescents.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_400_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691405PMC
July 2019

Identification of differentially expressed genes in small and non-small cell lung cancer based on meta-analysis of mRNA.

Heliyon 2019 Jun 14;5(6):e01707. Epub 2019 Jun 14.

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.

Lung cancer has the lowest survival rate spread globally resulting in a large number of deaths. This is attributed to insufficient measures such as lack of early detection and chemoresistance in the patients. It can be subdivided into two histological groups: Non-Small-Cell Lung Cancer (NSCLC), which is most prevalent (85% of all lung cancers) but less destructive; and Small-Cell Lung Cancer (SCLC), which is intermittently metastatic and less prevalent (15% of all lung cancers). The present study deals with the analysis of gene expression of two subtypes to identify the Differentially Expressed Genes (DEGs). For this study, we selected two datasets from the Omnibus database, which included 50 non-small cell lung cancer samples, 31 small cell lung cancer samples, and 48 samples from normal lung tissue. After DEGs identification using the meta-analysis approach, they were then subjected to further analysis following p-value adjustment via the Benjamini-Hochberg method. We identified 440 overexpressed and 489 underexpressed genes in NSCLC, and 489 overexpressed and 525 underexpressed genes in SCLC, compared with normal lung tissues. Furthermore, we identified 3 overlapping genes between upregulated DEGs in NSCLC and downregulated DEGs in SCLC; and 8 overlapping genes between upregulated DEGs in SCLC and downregulated DEGs in NSCLC. Accordingly, a Protein-Protein Interaction (PPI) network of the overlapping genes was generated, which contained a total of 261 genes, of which the top five were TRIM29, ANK3, CSTA, FGG, and AGR2. These five candidate genes reported herein may prove to be potential therapeutic targets.
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http://dx.doi.org/10.1016/j.heliyon.2019.e01707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580189PMC
June 2019

Circadian Preference, Sleep Quality, and Health-impairing Lifestyles Among Undergraduates of Medical University.

Cureus 2018 Jun 21;10(6):e2856. Epub 2018 Jun 21.

Center for Advance Research/Cytogenetic Unit, King George Medical University, Lucknow, IND.

Background/Aims Health-impairing lifestyle during adolescence is an important marker for poor health. An unhealthy lifestyle may lead to physical and psychological problems in adulthood. Most of the prior researches were done among the adult population. Therefore, we assessed the chronotype pattern and correlation of health-impairing lifestyles with sleep quality according to circadian typology in medical students. Material and Methods In this cross-sectional research, a total of 203 subjects were enrolled. All subjects were divided into definite evening chronotype (n = 73), intermediate chronotype (n = 87), and definite morning chronotype (n = 43). Electronic media use at bedtime and duration of media use, the timing of dinner, smoking, tobacco chewing, and alcohol consumption were assessed with the help of a preformed proforma. Physical activity, sleep quality, daytime sleepiness, and chronotype were assessed by International Physical Activity Questionnaire (IPAQ), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Score (ESS), and Morningness-Eveningness Questionnaire Self-assessment version (MEQ-SA), respectively. Results Subjects of the evening chronotype were suffering more with poor sleep quality. Evening chronotype had a significant (p < 0.05) positive correlation between poor sleep quality and sex, tobacco smoking, alcohol drinking, type of diet, and timing of dinner. Conclusion Circadian typology demonstrated the significant correlation of health-impairing lifestyles with sleep quality. From this observation, it might be a better way to plan their daily activities, in accordance with their chronotypes, benefiting not only their academic performance but also their quality of life.
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http://dx.doi.org/10.7759/cureus.2856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104894PMC
June 2018

Association of -330 interleukin-2 gene polymorphism with oral cancer.

Indian J Med Res 2017 Dec;146(6):730-737

Department of Anaesthesiology, King George's Medical University, Lucknow, India.

Background & Objectives: Cytokines play an important role in the development of cancer. Several single-nucleotide polymorphisms (SNPs) of cytokine genes have been reported to be associated with the development and severity of inflammatory diseases and cancer predisposition. This study was undertaken to evaluate a possible association of interleukin 2 (IL-2) (- 330A>C) gene polymorphisms with the susceptibility to oral cancer.

Methods: The SNP in IL-2 (-330A>C) gene was genotyped in 300 oral cancer patients and in similar number of healthy volunteers by polymerase chain reaction (PCR)-restriction fragment length polymorphism and the association of the gene with the disease was evaluated.

Results: IL-2 (-330A>C) gene polymorphism was significantly associated with oral cancer whereas it was neither associated with clinicopathological status nor with cancer pain. The AC heterozygous genotype was significantly associated with oral cancer patients as compared to controls [odds ratio (OR): 3.0; confidence interval (CI): 2.14-4.20; P<0.001]. The C allele frequency was also significantly associated with oral cancer (OR: 1.80; CI: 1.39-2.33; P<0.001). IL-2 (-330A>C) gene polymorphism was also associated with oral cancer in tobacco smokers and chewers.

Interpretation & Conclusions: Our results showed that oral cancer patients had significantly higher frequency of AA genotype but significantly lower frequency of AC genotype and C allele compared to controls. The IL-2 AC genotype and C allele of IL-2 (-330A>C) gene polymorphisms could be potential protective factors and might reduce the risk of oral cancer in Indian population.
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http://dx.doi.org/10.4103/ijmr.IJMR_1949_15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926344PMC
December 2017

Evaluation of Fastrach Laryngeal Mask Airway as an Alternative to Fiberoptic Bronchoscope to Manage Difficult Airway: A Comparative Study.

J Clin Diagn Res 2017 Jan 1;11(1):UC09-UC12. Epub 2017 Jan 1.

Professor, Department of Anaesthesiology, King George's Medical University , Lucknow, Uttar Pradesh, India .

Introduction: Awake intubation via Fiberoptic Bronchoscope (FB) is the gold standard for management of difficult airway but patients had to face problems like oxygen desaturation, tachycardia, hypertension and anxiety due to awake state. This study was conducted to assess feasibility of Fastrach Laryngeal Mask Airway (FLMA) to manage difficult airway as a conduit for intubation as well as for ventilation.

Materials And Methods: After ethical approval and informed consent, 60 patients with difficult airway were randomly enrolled in FB group and FLMA group. In FB group, patients were sedated with midazolam/fentanyl. Airway anaesthetization of oropharynx was done with xylocaine spray and viscous and larynx and trachea by superior laryngeal nerve block and transtracheal block respectively. In FLMA group, initially patients were induced with propofol for FLMA insertion then succinylcholine was given for Tracheal Intubation (TI). The first TI attempt was done blindly via the FLMA and all subsequent attempts were performed with fiberoptic guidance. Haemodynamic monitoring was done during induction, intubation, immediately post insertion and there after at five minutes interval for 30 minutes.

Results: All patients in the FLMA group were successfully ventilated (100%). In both the groups 28 (93.33%) patients were successfully intubated. However, first/second/third attempt intubation rate in FLMA vs FB group was 15 (50%) vs 13 (43.3%), 8 (26.66%) vs 10 (33.33%) and 5 (16.66%) in both groups respectively. Patients in the FLMA group were more satisfied with their method of TI and had lesser complications (p<0.05).

Conclusion: So the FLMA may be a better technique for management of patients with difficult airways.
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http://dx.doi.org/10.7860/JCDR/2017/22001.9284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324468PMC
January 2017

Genetic polymorphism of interleukin-10 (-A592C) among oral cancer with squamous cell carcinoma.

Arch Oral Biol 2017 May 7;77:18-22. Epub 2017 Jan 7.

Department of Anaesthesiology, King George Medical University, UP, Lucknow, India. Electronic address:

Objective: Interleukin-10 (IL-10) is a pleiotropic cytokine with either immunosuppressive or immunostimulative activities. It has been reported that in cancer, the promoter region polymorphism of IL-10 (-A592C) alters both the expression and serum levels of this cytokine. In the present study, we have addressed the question as to whether the single nucleotide polymorphisms (SNPs) at positions -592 A/C in the IL-10 gene promoter, could predispose an individual to oral squamous cell carcinoma (OSCC).

Design: We analyzed the genotype of the IL-10 (-A592C) gene, in 250 histopathologically confirmed OSCC patients and similar number of healthy volunteers taken as controls, in an Indian population by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Allele and genotype frequencies were analyzed by the Student's t-test and the chi-squared test, and strength of associations by the odds ratio (OR) with 95% confidence intervals.

Results: The genotype and allele distribution of IL-10 (-A592C) gene polymorphism was significantly different between OSCC cases and controls (genotype AA vs AC: OR 2.87; 95 % CI 1.50-5.48; p=0.0016 and AA vs CC: OR 4.08; 95 % CI 1.98-8.41; p=0.0002). The -592 C alleles were found to be significantly different among OSCC cases and controls (OR: 1.44, 95% CI: 1.12-1.85, p<0.0051).

Conclusions: The IL-10 gene promoter region (-592) A/C polymorphism is significantly associated with reduced risk of OSCC. The OSCC group had a significantly greater frequency of genotype AA as compared to control group.
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http://dx.doi.org/10.1016/j.archoralbio.2016.12.011DOI Listing
May 2017

Transdermal Buprenorphine Patches for Postoperative Pain Control in Abdominal Surgery.

J Clin Diagn Res 2016 Jun 1;10(6):UC05-8. Epub 2016 Jun 1.

Professor, Department of Anaesthesiology, King George's Medical University , U.P., Lucknow, India .

Introduction: Buprenorphine is a semi-synthetic derivative of thebaine; its low concentration is sufficient to provide effective pain relief.

Aim: To evaluate the efficacy of transdermal buprenorphine patch in postoperative pain management.

Materials And Methods: After ethical approval and taking informed consent from the patients, they were randomized into three groups (n=30 in each group) using a computer generated random number table. Group A: placebo patch; Group B: buprenorphine (10mg) patch and Group C: buprenorphine (20mg) patch. Haemodynamic and analgesic effects were compared by using analysis of variance (ANOVA) followed by Turkey's post hoc test. The proportion of side effects was compared using the Chi-square test.

Results: Haemodynamic changes were not statistically different in all the three groups A, B and C, whereas at the end of surgery VAS score of Group A subjects was significantly higher (4.93±0.98) as compared to Group B (1.73±0.64) and Group C (1.40±0.50). On 2(nd) postoperative day, no pain was reported by the Group C patients and on 4(th) day after surgery, no pain was reported by Group B patients.

Conclusion: The transdermal buprenorphine patch (20mg) was effective in attenuating postoperative pain, maintaining haemodynamic stability requiring no rescue analgesia, with fewer postoperative rescue analgesic requirements in low dose of buprenorphine patch (10mg) group.
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http://dx.doi.org/10.7860/JCDR/2016/18152.7982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963743PMC
June 2016

Multimodal versus Conventional Approach for Postoperative Pain Relief in Oral Cancer Patients.

J Clin Diagn Res 2016 Jan 1;10(1):UC05-8. Epub 2016 Jan 1.

Professor, Department of Anaesthesiology, King George's Medical University , Lucknow, U.P., India .

Introduction: Multimodal analgesia includes regional anaesthesia in the form of nerve block may improve recovery along with optimal rehabilitation and early resumption of day-to-day activity following major surgery. Conventional general anaesthesia consists of premedication, induction, intubation and maintenance.

Aim: The aim of the study is to compare the multimodal versus conventional approach in oral cancer surgery.

Materials And Methods: The patients were randomly allocated into three groups, 30 patients in each group using the computer generated random table to one of the following groups: Group A: Fentanyl 1 μg/kg, Group B: Fentanyl 1 μg/kg + bupivacaine local infiltration, Group C: Fentanyl 1 μg/kg + bupivacaine local infiltration + Dexemedetomidine infusion (Loading 0.5 μg/kg, Maintenance 0.2μg/kg/hr).

Results: No significant (p>0.05) difference was found in mean arterial pressure and heart rate at different time intervals among the groups. The VAS was lower in Group C than Group B and A. The ramsay sedation scale was higher in Group C than Group B and A. The rescue analgesic for 24 hour was lower in Group C than Group B and A. The time of first time analgesia requirement was significantly (p=0.001) higher in Group C than Group B and A. The rescue analgesic was significantly (p=0.001) lower in Group C (39.29±19.67) than Group B (68.33±18.49) and A (160.83±35.16).

Conclusion: Multimodal analgesia has beneficial haemodynamic effects during oral cancer surgery with reliable postoperative analgesia and sedation and less postoperative complication. Dose of drugs used in our study is not associated with any major adverse effect.
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http://dx.doi.org/10.7860/JCDR/2016/13785.7027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740679PMC
January 2016

Association of Genetic Polymorphism in the Interleukin-8 Gene with Risk of Oral Cancer and Its Correlation with Pain.

Biochem Genet 2016 Feb 10;54(1):95-106. Epub 2015 Dec 10.

Department of Biochemistry, King George's Medical University, Lucknow, UP, 226003, India.

Oral cancer is a multifactorial disease process and involves complex interactions between gene to gene and gene to environmental factors. Interleukin 8 (IL-8), a pro-inflammatory cytokine, having angiogenic activity with elevated expression in tumor cells, is reported to play an essential role in oral cancer development. This study was conducted with the aim to investigate the role of IL-8 (-A251T) gene polymorphism in susceptibility, progression, and self-reporting pain in oral cancer. The single nucleotide polymorphisms of the IL-8 (-A251T) gene were screened in 300 patients with oral cancer and 300 healthy controls, by polymerase chain reaction-restriction fragment length polymorphism. Genotype and allele frequencies were evaluated by chi-square test and odds ratio (OR) with 95% confidence intervals (CIs) were used to evaluate the strength of associations. The results of the study demonstrated that IL-8 (-A251T) gene polymorphism was significantly associated with susceptibility of oral cancer, whereas its correlation with clinico-pathological status or pain due to oral cancer could not be established. The AT heterozygous (OR 5.31; CI 3.38-8.34; p 0.0001) and AA homozygous (OR 2.89; CI 1.76-4.75; p 0.0001) had a greater risk for oral cancer compared to TT homozygous. Furthermore, significantly increased values of A allele frequencies compared to T allele were observed in all patients (OR 1.56; CI 1.24-1.96; p 0.0002). Tobacco chewing and smoking were also found to influence the development of oral cancer and increased the incidence of pain in oral cancer patients. The findings of this study suggest that the IL-8 (-A251T) gene polymorphism may be associated with increased risk of oral cancer.
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http://dx.doi.org/10.1007/s10528-015-9704-yDOI Listing
February 2016

Association of interleukin-6 genetic polymorphisms with risk of OSCC in Indian population.

Meta Gene 2015 Jun 15;4:142-51. Epub 2015 May 15.

Department of Biochemistry, King George's Medical University, UP, Lucknow, India.

Purpose: Interleukin-6 (IL-6) encodes a cytokine protein, which causes inflammation, maintains immune homeostasis and plays an essential role in oral pathogenesis. The aim of this study was to evaluate the association between IL-6 (- 174 and - 572) G/C promoter gene polymorphisms and risk of OSCC among Indians.

Methods: Single nucleotide polymorphism in IL-6 genes was genotyped in OSCC patients and healthy controls by PCR-RFLP method. Genotype and allele frequencies were analyzed by chi-square test and strength of associations by odds ratio with 95% confidence intervals.

Results: Frequency distribution of IL-6 (- 174) G/C gene polymorphism was significantly associated with OSCC patients in comparison to healthy controls (OR: 0.541, CI: 0.356-0.822; p: 0.004. However, frequency of IL-6 (- 572) G/C gene polymorphism was not significantly associated with OSCC patients (p > 0.05).

Conclusion: The genotype GC and allele C of IL-6 (- 174) G/C gene polymorphism play a significant role in OSCC susceptibility.
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http://dx.doi.org/10.1016/j.mgene.2015.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436510PMC
June 2015

Association of TNF-α (-238 and -308) promoter polymorphisms with susceptibility of oral squamous cell carcinoma in North Indian population.

Cancer Biomark 2015 ;15(2):125-31

Department of Biochemistry, King George's Medical University, Lucknow, India.

Background: The pro-inflammatory cytokines play an essential role in immune response and are involved in a variety of inflammatory and infectious disease. Tumor necrosis factor alpha (TNF-α) gene polymorphism has been a potential determinant of susceptibility to various types of cancer.

Objective: To evaluate the association of TNF-α gene promoter (-238) G/A and (-308) G/A polymorphisms with the susceptibility of OSCC patients in North Indian population.

Methods: A total 272 patients with OSCC and 185 healthy volunteers were genotypes for the TNF-α (-238) G/A and (-308) G/A gene polymorphism. Genotypes were identified by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). Genotype frequencies were evaluated by Chi-square test and Odds ratio (OR) relative risk.

Results: TNF-α (-238) G/A polymorphism was significantly associated with OSCC patients as compared to healthy volunteers (GG vs. GA: OR=0.3500, 95% CI=0.1289-09502; p=0.036; G vs. A: OR=0.3589 1.477, 95% CI=0.1335-0.9652; p=0.0386). No significant association was found in TNF-α (-308) G/A gene polymorphism with OSCC patients and controls.

Conclusions: We conclude that the TNF-α (-238) G/A polymorphism was significantly associated with OSCC however TNF-α (-308) G/A polymorphism was not associated in OSCC patients.
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http://dx.doi.org/10.3233/CBM-140444DOI Listing
February 2016
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