http://nopr.niscpr.res.in/handle/123456789/61181 2026-10-11T02:57:32Z http://nopr.niscpr.res.in/handle/123456789/61191 Title: A comparative computational approach on the most deleterious missense variant in Connexin 43 protein and its potent inhibitor analysis Authors: Katturajan, Ramkumar; Medha, Tamma; Karra, Sakshi; R, Vidya; Prince, Sabina Evan Abstract: Intercellular communication between the cell plays an essential role in cell growth and cell formation, including migration, metabolism, and cell differentiation. Cell function and tissue homeostasis are maintained through gap junction intercellular communication (GJIC), thus regulating connexin hemichannels. Mis regulation of such connexin, especially connexin (Cx) 43, affects a comprehensive process, including cell differentiation, inflammation, and cell death. Mis regulation may be due to the missense variant in Cx43. Thus, we screened the complete set of mutations from public mutational databases and obtained 219 missense variants, which were then classified based on their pathogenicity, functional impact, stability, conservation, and physiochemical properties. Variant L214P was scrutinized to have the most deleterious, which was then modelled using the I-TASSER server and performed molecular docking analysis to screen potent inhibitors. The compound Kanamycin, Ginsenoside, and Astragaloside IV have better interactions with Cx43 mutant with a maximum of 5 hydrogen bonds. Ginsenoside is a compound that follows a Lipinski rule of five. Thus, the result obtained from this study suggests that Ginsenoside would be a better potent inhibitor for native and mutant Cx43. Page(s): 7-25 2023-01-01T00:00:00Z http://nopr.niscpr.res.in/handle/123456789/61190 Title: Moringa oleifera seeds attenuate benzene-induced alterations in lipid peroxidation and antioxidant enzymes in liver and kidney tissues of Wistar rats Authors: Rajkumar, R; Ilango, B; Vinothkumar, K; Savidha, R; Senthilkumar, S; Ezhilarasan, D; Sukumar, E Abstract: Benzene is a notorious toxicant that is responsible for a host of diseases including leukemia. Its concentration in the environment is increasing day-by-day due to excessive automobile use, accelerated industrial activities and cigarette smoke. The awareness on the harmful effects of benzene on health is limited and no antidote has been reported yet. In this study, an attempt has been made to find out a suitable remedy to overcome benzene toxicity in a living organism from a natural source with the seeds of the plant Moringa oleifera (MO). Thirty six Wistar rats were considered for the study and divided into six groups (n=6). While group I remained as control with normal animals, those in groups II – VI received benzene by oral route (800 mg/kg body weight) for 28 consecutive days. On day 29, the benzene-treated animals in groups III – VI received respectively the standard drug ascorbic acid (AA, 25 mg/kg body weight) and MO (50, 100 and 200 mg/kg body weight) for the following 7 days. Group II rats that received only benzene served as negative control without any treatment. On day 36, all the animals were sacrificed and vital organs liver and kidney were removed for studying lipid peroxidation (LPO) and antioxidant markers [Superoxide dismutase (SOD), Total reduced glutathione (TRG), Glutathione peroxidase (GPx) and Catalase (CAT)] in addition to histopathological changes in the tissues. The results of the study revealed that significant changes occurred in the above parameters due to benzene dosing to animals were reverted to near normal values on MO administration in the liver and kidney tissues as compared to untreated animals, suggesting MO’s pro-active role in attenuating benzene toxicity. Page(s): 26-30 2023-01-01T00:00:00Z http://nopr.niscpr.res.in/handle/123456789/61189 Title: Simultaneous detection of thirteen exons of dystrophin gene by optimized multiplex PCR assay to screen Duchenne/Becker muscular dystrophy Authors: Trivedi, Pooja G; Gajera, Jaydeep B; Ghanchi, Fesal I; Sindhav, Gaurang M Abstract: Advancements in Polymerase Chain Reaction (PCR) technology and other techniques like Deoxyribonucleic acid (DNA) signal and target amplification have become key procedures in molecular diagnostics. PCR enables the synthesis of nucleic acids in vitro through which a DNA segment can be specifically replicated in a semiconservative way that sets forth deletion and mutation analysis. Multiplex PCR (M-PCR) is beneficial over standard and long PCR as this can amplify more than one locus using the respective primer sets. In harmony with this, the present study aimed to optimize M-PCR followed by its chemistry and condition to screen Duchenne Muscular Dystrophy (DMD) [OMIM #310200] and Becker Muscular Dystrophy (BMD) [OMIM #300376]. Muscular Dystrophies (MDs) are a broad group of hereditary, progressive, and degenerative disorders of muscles. X-linked recessive D/BMD are caused by mutation/s in the dystrophin gene [OMIM #300377] that encodes for dystrophin protein [UniProt#P11532]. As dystrophin is the human metagene with 79 exons, mutational analysis is very challenging. Chamberlain set (10 plex), Beggs set (9 Plex), and Kunkel set (7 Plex) is used for many years to diagnose this condition. However, in this study, Beggs set is customized with 13 exons to screen DMD gene mutation in a single reaction. Optimization of M-PCR was designed with many physicochemical parameters. According to the literature and after many appraisals the present study demonstrated the most sufficient concentration of various chemical components and optimal cycling conditions to optimize the modified Beggs set (13 Plex). 50 μL PCR reaction includes primer(s) (0.3–0.5 μM each), dNTP mixture (160 μM each), Dream Taq buffer (1X), Taq DNA polymerase (6U/50 μL), DNA template (250 ng/50 μL), BSA (0.4 μg/μL), and MgCl2 (1.4 mM). To get the most effective results cyclic conditions obtained were 10 min initial denaturation at 94°C, 62°C annealing temperature, and 35 PCR cycles at 72°C extending temperature. Consequently, the study successfully formulated a less expensive and simple approach for >3000 bp that was used to screen D/BMD. Finally, a developed M-PCR mix with a unique combination of specificity and sensitivity coupled with great flexibility has led to a true revolution in molecular diagnostics. Page(s): 31-42 2023-01-01T00:00:00Z http://nopr.niscpr.res.in/handle/123456789/61186 Title: Assessment of YME1L and mitofusin2 as a possible diagnostic and/ or therapeutic target in hepatocellular carcinoma Authors: Abdel-Hamid, Nabil Mohie; Abass, Shimaa A; Eldomany, Ramadan A; Zakaria, Sherin Abstract: The contribution of mitochondrial dynamics to the development and progression of hepatocellular carcinoma (HCC) remains controversial. Accordingly, the present study tries to illustrate the role of mitochondrial dynamics proteins (mitofusin-2 (Mfn2) and YME1L) in hepatocarcinogenesis. Five groups were used: the control group and three HCC groups (after 8, 16, and 24 weeks from DENA induction). The last group was treated with Sorafenib (SP) (10 mg/kg), via oral gavage for 4 weeks after cancer induction. This study revealed that Mfn-2 was downregulated and YME1l was overexpressed in different HCC groups. This dysregulation of mitochondrial dynamics proteins was associated with high hepatic levels of cyclin D1, MMP-9, and MDA and overexpression of ki67 as well as decreasing the hepatic expression of tissue inhibitor of matrix metalloproteinase-3 (Timp-3) and Bax. To confirm the possible role of Mfn2 and YME1L in HCC, we assessed the effect of sorafenib on these parameters and its related HCC characteristics. Sorafenib corrected the level of Mfn2 and YME1L and decreased tumor cell proliferation as well. We also elucidated that mitochondrial dynamics proteins (Mfn2 and YME1L) could be a good therapeutic target for HCC. Page(s): 43-54 2023-01-01T00:00:00Z