http://localhost:8080/xmlui/handle/123456789/193 2026-04-26T08:24:33Z 2026-04-26T08:24:33Z Raza, Asif Kohila, V. Ghosh, Siddhartha Sankar http://localhost:8080/xmlui/handle/123456789/3251 2025-05-02T09:09:18Z 2015-01-01T00:00:00Z

Title: Redesigned Escherichia coli cytosine deaminase: A new facet of suicide gene therapy Authors: Raza, Asif; Kohila, V.; Ghosh, Siddhartha Sankar Abstract: Background The Escherichia coli cytosine deaminase (CD)/5-fluorocytosine(5-FC) approach emerges as a potential aid for suicide gene therapy in the fieldof modern cancer treatment. However, the poor binding affinity of CD towards5-FC compared to the natural substrate cytosine limits its application for suc-cessful suicide gene therapy. Redesigning a bacterial mutant CD with site-directed mutagenesis showed higher potency compare to wild-type CD (wtCD)in vitro. In the present study, we conducted a comparative analysis of F186Wmutant and wtCD in a human lung cancer cell line (A549).Methods and Results A comparative investigation was initiated with cellviability analyses by MTT and trypan blue dye exclusion assays on A549 cellstransfected with wtCD and F186W genes. The mode of cell death wasconfirmed by acridine Orange/ethidium Bromide dual staining. Furthermore,flow cytometric assessments were performed by cell cycle analysis and caspase3 assay. The experimental results showed a drug dependent decrease in cellviability; interestingly, mutant (F186W) reached IC50 at a much lower concen-tration of prodrug (5-FC) than wtCD. Cell cycle analysis showed that G1 arrestof a larger population of 5-FC treated F186W transfected cells, in contrast tothat of wtCD under similar conditions. The caspase 3 assay revealed progres-sion and execution of apoptosis.Conclusions We report a novel bacterial CD mutant that provided a superioralternate to the wtCD suicide gene. The F186W mutant required a much lowerdose of 5-FC to reach its IC 50 , thus minimizing the systemic side effects of largedoses of 5-FC as required for wtCD. Description: NITW

2015-01-01T00:00:00Z Baadhe, R.R. Potumarthi, R. Mekala, N.K. http://localhost:8080/xmlui/handle/123456789/3241 2025-05-01T10:43:12Z 2014-01-01T00:00:00Z

Title: Significance of Biotic Factors in Mesenchymal Stem Cell Fate in Regenerative Medicine Authors: Baadhe, R.R.; Potumarthi, R.; Mekala, N.K. Abstract: Stem and progenitor cell research is a complex and exciting field which promises curative discoveries in numerous areas including cancer, diabetes, and regenerative medicine. Use of biotic factors or growth factors has played an essential role in the development of stem cell research. These biologically active components have been administered into stem cells either to improve or maintain the stem cell proliferation, or to encourage controlled differentiation into more defined cell types. Small molecules such as 6-Bromoindirubin-3´-oxime (BIO), cardiogenol-C, etc can help stem cell research by controlling or influencing the regulatory changes in a controlled manner and to help understand the mechanisms during stem cell differentiation. Extra cellular matrix (ECM) is another significant biotic factor, which mediates cell and tissue behavior by influencing cell-matrix interactions. Thus, in this review we would like to emphasize significance of various growth factors in stem cell research Description: NITW

2014-01-01T00:00:00Z Korrapati, N. Nanganuru, H.Y. http://localhost:8080/xmlui/handle/123456789/3240 2025-05-01T09:43:22Z 2014-01-01T00:00:00Z

Title: A Comprehensive Review on Perfusion Method Development for Bone Marrow Collection and Stem Cell Transplantation Authors: Korrapati, N.; Nanganuru, H.Y. Abstract: Bone marrow transplant (BMT) is done by the replacement of damaged bone marrow with healthy one. These healthy bone marrow cells (BMCs) are usually collected from the crest of the Ilium in humans hence these cells are used to replace damaged ones in the treatment of bone marrow related diseases such as leukemia, aplastic anemia, congenital immunodeficiency and autoimmune diseases. Even though there are different methods, perfusion method is one of the simple, safe and less contaminated methods used to harvest BMCs and it can reduce the risk in allogenic BMT. Intra bone marrow – bone marrow transfer (IBM-BMT) is one of the best procedures for allogenic BMT. Due to enlisting of hematopoietic stem cells and mesenchymal stem cells, which are derived from donor, this method has distinguishable advantages in allogenic BMT. In this paper the perfusion method (for harvesting BMCs) and IBM-BMT (for their transplantation) have been critically reviewed and showed that both methods are together will become an effective combination in allogeneic BMT. Description: NITW

2014-01-01T00:00:00Z Arun, D. Rath, Soumya Lipsa http://localhost:8080/xmlui/handle/123456789/3237 2025-03-04T05:04:31Z 2025-01-01T00:00:00Z

Title: Structural analysis of the impact of germline mutations of p16 in melanoma prone families Authors: Arun, D.; Rath, Soumya Lipsa Abstract: Cyclin-dependent kinases (CDKs), play essential roles in cell cycle progression. CDK activity is controlled through phosphorylation and inhibition by CDK inhibitors, such as p16. Mutations in p16 can lead to diseases such as cancer. This study examines a series of p16 mutants and their molecular interactions with CDK4 using modelling, molecular dynamics simulations, and docking studies. Despite no significant structural changes in p16 due to mutation, the binding affinity was found to be affected, correlating with conservation scales. Simulations revealed that specific mutations, such as G23D, P114S, and A60V resulted in loss of binding to CDK4, while others like R24Q and G67R showed partial loss. Surface electrostatics emphasised the significance of a positive patch on the binding surface of p16 that faces the CDK4 which was directly impacted due to mutations. Additionally, the partial binding mutants were found to have a lower stability compare to the Wildtype p16/CDK4 complex through the free energy landscape calculations. These findings provide useful insights into the molecular mechanisms by which p16 mutations influence CDK4 binding, potentially informing therapeutic strategies. Description: NITW

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