Background and Objective:Persistent high risk human papilloma virus (HPV) infection is probably the best predictor of increased risk of cervical cancer, but expression of certain markers of cell proliferation and apoptosis have been studied. The present study was conducted to evaluate the expression of p53 and bcl2 in premalignant and malignant lesions of cervix and its correlation with HPV type 16 and 18.Materials and Methods:The study comprised of 35 cases (including 24 prospective cases and 11 retrospective cases) of premalignant and malignant lesions of the cervix. Slides were stained with Hematoxylin and Eosin and p53, bcl2 (immunohistochemistry), HPV 16 and HPV 18 (in situ hybridization).Results:p53 positivity was seen in 8/19 (42.1%) cases of cervical intraepithelial neoplasia (CIN) and 8/16 (50%) cases of carcinoma cervix, the difference not significant statistically. The difference in bcl2 expression in CIN versus carcinoma cervix (84.21% vs. 43.75%) was statistically significant (P = 0.030). There was no significant difference between p53 and bcl2 expression and the stage and grade of the tumors. Seven out of 19 cases of CIN (36.84%) were positive for HPV 16/18 infection and 8/16 cases (50%) of carcinoma cervix were HPV positive (P = 0.628).Conclusions:No significant association was found between HPV 16/18 infection and p53 and bcl2 expression in premalignant and malignant lesions of uterine cervix. Although, bcl2 staining showed a significant difference between CIN and carcinoma cervix, a larger case series is required to assess the association between HPV infection and overexpression of p53 and bcl2 proteins in these lesions.
Discovering a potential drug for HCV treatment is a challenging task in the field of drug research. This study initiates with computational screening and modeling of promising ligand molecules. The foremost modeling method involves the identification of novel compound and its molecular interaction based on pharmacophore features. A total of 197 HCV compounds for NS3/4A protein target were screened for our study. The pharmacophore models were generated using PHASE module implemented in Schrodinger suite. The pharmacophore features include one hydrogen bond acceptor, one hydrogen bond donor, and three hydrophobic sites. As a result, based on mentioned hypothesis the model ADHHH.159 corresponds to the CID 59533233. Furthermore, docking was performed using maestro for all the 197 compounds. Among these, the CID 59533313 and 59533233 possess the best binding energy of −11.75 and − 10.40 kcal/mol, respectively. The interactions studies indicated that the CID complexed with the NS3/4A protein possess better binding affinity with the other compounds. Further the compounds were subjected to calculate the ADME properties. Therefore, it can be concluded that these two compounds could be a potential alternative drug for the development of HCV.
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