Biology subjects

Nanda, R.

Publications and source records attributed to Nanda, R..

22 records · Page 2Linked to original sources

bioRxiv2020

RRBP1 rewires cisplatin resistance in Oral Squamous Cell Carcinoma by regulating YAP-1

Cisplatin-based chemotherapy still remains as one of the primary treatment modalities for OSCC. Several OSCC patients experience relapse owing to development of chemoresistance. To identify key resistance triggering molecules, we performed global proteomic profiling of human OSCC lines presenting with sensitive, early and late cisplatin resistance patterns. From the proteomic profiling study, human RRBP1 was identified to be upregulated in both early and late cisplatin-resistant cells with respect to the sensitive counterpart. Analysis of OSCC patient sample indicates that RRBP1 expression is elevated in chemotherapy-non-responder tumors as compared to chemotherapy-naive tumors. Knocking out RRBP1 resulted in restoring cisplatin mediated cell death in chemoresistant lines and patient derived cells (PDC). Mechanistically, RRBP1 regulates YAP-1 to induce chemoresistance in OSCC. The chemoresistant PDC xenograft data suggests that knock out of RRBP1 induces cisplatin mediated cell death and facilitates a significant reduction of tumor burden. We also found Radezolid, a novel oxazolidinone antibiotic represses the expression of RRBP1 and restores cisplatin-induced cell death in chemoresistant OSCC. This unique combinatorial approach needs further clinical investigation to target advanced OSCC. Here with for the first time, we uncover the novel role of RRBP1 as potential modulator of cisplatin resistance in advanced OSCC.

cancer biology↗

bioRxiv2019

Anti-inflammatory Role of Curcumin in LPS Treated A549 cells at Global Proteome level and on Mycobacterial infection.

A diet derived agent Curcumin (Diferuloylmethane), demonstrated its clinical application in inflammation, infection and cancer conditions. Nevertheless, its impact on the proteome of epithelial cells of non-small cell lung carcinoma (NSCLC) is yet to be explored. We employed a stable isotope labeling method for cell culture (SILAC) based relative quantitative proteomics and informatics analysis to comprehend global proteome change in A549 cells treated with curcumin and/or Lipopolysaccharide (LPS). Pretreated A549 cells were infected with Mycobacterium tuberculosis H37Rv strain to monitor bacterial load. With exposure to curcumin and LPS, out of the 1492 identified proteins, 305 and 346 proteins showed deregulation respectively. The expression of BID and AIFM1 mitochondrial proteins which play critical role in apoptotic pathway were deregulated in curcumin treated cells. Higher mitochondria intensity was observed in curcumin treated A549 cells than LPS treatment. Simultaneous treatment of curcumin and LPS neutralized the effect of LPS. Curcumin and/or LPS pretreated A549 cells infected with H37Rv, showed successful bacterial internalization. LPS treated A549 cells after infection showed increased bacterial load than curcumin compared to non-treated infected cells. However, simultaneous treatment of curcumin and LPS neutralized the effect of LPS. This study generated molecular evidence to deepen our understanding of the anti-inflammatory role of curcumin and may be useful to identify molecular targets for drug discovery.

biochemistry↗

bioRxiv2019

Untargeted metabolite analysis of Ocimum leaves shows species specific variations

Tulsi (Ocimum species), the queen of herbs is a common ingredient in beverages with perceived health benefits. Recently published Ocimum genome highlighted the presence of several genes that contributes to important phytochemicals but a comprehensive metabolite profiling to study the water soluble metabolites of Ocimum is lacking. In this study, untargeted metabolic profiling of hot water extract of fresh and air dried leaves of O. basilicum, O. sanctum and O. kilimandscharicum species employing gas chromatography and mass spectrometry (GC-MS) was attempted. Analysis of hot water extracts of Ocimum leaves will provide details of molecules consumed and species specific differences, if any. Several metabolic features including amino acids (glycine, serine glutamate), organic and other acids (succinic acid, fumaric acid, 4-amino butanoic acid), sugars and their derivatives (glucose, sucrose, mannitol, fructose) and secondary metabolites (shikimic acid, quinic acid, catechol, gamma amino butyric acid, eugenol) were identified. Multivariate statistical analysis of GC-MS data indicated several species specific metabolic similarities and differences. Based on variable importance parameter score of >1, it was observed that in case of air dried extracts, glucose, fumaric acid, and D-mannitol displayed as important variables for species specific variation. Whereas in case of fresh leaves extracts, the variation was prominent due to xylose, D-allose and an unknown metabolic feature detected at 24 min (metabolite@24 with highest m/z 75). Phytochemical phenotype of Ocimum leaves not only shows species specific variations but these may partly explain their difference in taste and health benefits from their use as hot beverages.

biochemistry↗

bioRxiv2019

Diurnal variations in serum metabolites of wintering redheaded buntings.

Daily behavioural and physiological changes in bird may reflect in biofluid metabolite composition. Locomotor activity, food intake and body temperature of group (n=7) of male migratory redheaded buntings held under short days (8L:16D, SD) were monitored besides blood sampling at midday (ZT4: 4 hours zeitgeber time starting ZT0 as lights on) and midnight (ZT16). The birds exhibited higher activity and increased feeding during daytime with negligible activity and feeding at night. Gas chromatography mass spectrometry and chemo-metric analyses of bird serum revealed higher levels of lipid (palmitic, oleic and linoleic acids) and protein (uric acid and proline) catabolites in daytime serum samples as compared to night samples. Higher night-time levels of short chain fatty acids indicated utilization of glucose and lipolysis in night fasted birds. High night-time levels of taurine, a sulphur amino acid has adaptive advantage to night migratory song birds. The diurnal differences in metabolite patterns suggests differential energy expenditure during day and renders survival benefit to buntings as night migrants. We propose a GCMS method that could be useful to unravel different annual life-history stages including migration.

animal behavior and cognition↗