Browsing by Author "G. Narayan"

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Activation of Toll-like receptors in meconium aspiration syndrome
(Nature Publishing Group, 2018) V. Anand; S. Basu; S.S. Yadav; G. Narayan; B.D. Bhatia; A. Kumar
Objective:Meconium aspiration syndrome (MAS) is a common cause of neonatal morbidity and mortality. Incomplete understanding of the pathogenesis of MAS has hindered the development of specific therapies. We hypothesized that activation of Toll-like receptors (TLRs) might play a role in the pathogenesis of MAS. The present study evaluated the expression of TLR 1, 4, 7, 8 and 9 in neonates with MAS.Study Design:The study included 39 neonates with MAS and 17 healthy gestational age-matched neonates as controls. Neonates with maternal chorioamnionitis, perinatal asphyxia, sepsis and congenital malformations were excluded. Good-quality total RNA from umbilical cord blood was reverse transcribed to prepare cDNA using Bio-Rad reverse transcription kit. This cDNA was used to study the expression status of TLR 1, 4, 7, 8 and 9 by real-time quantitative polymerase chain reaction.Results:Compared with controls, TLR1 and TLR4 were highly expressed, TLR9 was moderately expressed, TLR7 was weakly expressed and TLR8 expression was neutral in neonates with MAS. Within the MAS group, no difference in TLR expression was observed with respect to consistency of meconium, severity of the disease, oxygenation index and outcome.Conclusion:There is activation of TLRs in neonates with MAS. We speculate that these TLRs probably act as endogenous ligands for various components of meconium that initiate the inflammatory cascade of MAS and contribute to its pathogenesis. © 2018 Nature America, Inc., part of Springer Nature. All rights reserved.
Curcumin-mediated reversal of p15 gene promoter methylation: Implication in anti-neoplastic action against acute lymphoid leukaemia cell line
(Charles University, 2015) V. Sharma; A.K. Jha; A. Kumar; A. Bhatnagar; G. Narayan; J. Kaur
Curcumin has been documented to exert anticancer effects by interacting with altered proliferative and apoptotic pathways in cancer models. In this study, we evaluated the potential of curcumin to reverse promoter methylation of the p15 gene in Raji cells and its ability to induce apoptosis and genomic instability. Anti-neoplastic action of curcumin showed an augmentation in reactive oxygen species (ROS) and cell cycle arrest in G1 phase. Subsequently, curcumin-exposed Raji cells showed structural abnormalities in chromosomes. These observations suggest that curcumin also causes ROS-mediated apoptosis and genomic instability. The treatment of Raji cell line with 10 μM curcumin caused hypomethylation of the p15 promoter after six days. Hypomethylation of p15 was further found to be favoured by down-regulation of DNA methyltransferase 1 after 10 μM curcumin treatment for six days. Methylation-specific PCR suggested demethylation of the p15 promoter. Demethylation was further validated by DNA sequencing. Reverse-transcription PCR demonstrated that treatment with curcumin (10 μM) for six days led to the up-regulation of p15 and down-regulation of DNA methyltransferase 1. Furthermore, curcumin-mediated reversal of p15 promoter methylation might be potentiated by down-regulation of DNA methyltransferase 1 expression, which was supported by cell cycle analysis. Furthermore, curcumin acts as a double-pronged agent, as it caused apoptosis and promoter hypomethylation in Raji cells. © 2015, Charles University. All rights reserved.
Expression of p27 and p16 and their clinical significance in gastric cancer
(Springer Science and Business Media Deutschland GmbH, 2021) S. Kumari; P. Kumar; M. Kumar; S. Singh; G. Narayan
Background: Deregulated expression of cell cycle regulators p27 and p16 is associated with cancer progression. p27kip1 and p16INKa are a cyclin dependent kinase inhibitor whose major target is the cyclinE/CDK2 and cyclinD/CDK4/6 complex, respectively, that governs cell cycle transition from late G1 to S phase. Methods: We recruited biopsies of a total of 84 subjects including 72 primary tumor biopsies from histopathologically proven gastric carcinoma, 8 adjacent controls and 12 independent controls. We used gastric cancer cell line, AGS, for validation of our data. Expression profiling at transcript level was done by semi-quantitative RT-PCR and at proteome level by immunohistochemistry and immunofluorescence. Receiver operator characteristics analysis was done for determining the diagnostic utility of p27 and p16 with respect to the sensitivity and specificity. Results: We demonstrate that p27 and p16 are frequently over expressed in early stages of gastric carcinoma. Our semi-quantitative data show a significant upregulation of p27 (Mean ± SEM, 0.4771 ± 0.0895; p = 0.0001) and p16 (Mean ± SEM, 0.4676 ± 0.04305; p = 0.0001) at mRNA level. Concordant to semi-quantitative data, immunohistochemistry data also showed a significant upregulation of p27 (Mean ± SEM, 196.4 ± 10.84; p < 0.0001) and p16 (Mean ± SEM, 100.4 ± 23.71; p < 0.0001) at protein level. Conclusions: The present study showed that the significant upregulation of p27 and p16 were associated with early events in gastric carcinogenesis. Our data suggests that clinical correlation of these differentially expressed genes may be useful as diagnostic biomarkers for early detection of gastric carcinoma and promising therapeutics target for GC patients. © 2020, Federación de Sociedades Españolas de Oncología (FESEO).