Objective: Our study was aimed to understand the importance of FA-BRCA pathway genes in cervical carcinogenesis and their association with the prognosis of the disease. Material and methods: we analysed the molecular profiles of the key regulatory genes of FA-BRCA pathway (BRCA1, BRCA2, FANCC, FANCD2) in 109 cervical lesions at different clinical stages and validated in different bioinformatical analysis as well. The results were next correlated with different clinicopathological parameters. Furthermore, the drug tolerance mechanism of the genes was characterized by treating two CACX cell lines (SiHa and HeLa) in presence of the chemotherapeutic drug cisplatin. Result: Our data showed that the expression pattern (mRNA/Protein) of the genes of FA-BRCA pathway was gradually decreased from normal cervical epithelium to the development of carcinogenesis, also validated in different GEO datasets. Further, in-depth look into the results revealed that genetic (deletion) and epigenetic alterations (promoter methylation) [30 to 55 %] of the genes was strongly correlated with their reduced expression and development of cervical cancer among the patients, resulting in worst 5-year overall survival trend. Incidentally, the prevalence of promoter methylation in both plasma and respective tumour DNA of invasive cervical carcinoma patients implicated its prognostic importance and association with disease recurrence in this study. In continuation of that, our in-vitro study revealed that cisplatin could upregulate the FA-BRCA pathway genes gradually with increasing drug concentrations in the CACX cell lines through promoter hypomethylation due to reduced expression of DNMT1, indicating the intrinsic mechanism of drug tolerance of residual tumour cells of the disease.Conclusion: Our data showed that the inactivation of FA-BRCA pathway was associated with the development and prognosis of CACX. Up-regulation of the pathway genes in presence of cisplatin in the CACX cell lines suggested a plausible mechanism of non-responsiveness to the therapy.

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Herein, we reported an effective one‐pot protocol to synthesize quinazolinone fused N‐heterocyclic scaffold, structurally similar to the natural product Luotonin and Rutaecarpine by Pd(OAc)2/Ag(OAc)‐promoted intramolecular dehydrogenative cross‐coupling (DCC). The structure of all the compounds has been confirmed unambiguously by NMR, mass, and XRD. The electronic effect of the substituents attached to the backbone of the starting material was thoroughly investigated. The outcome of the reaction is highly dependent on the substrate structure and pH of the medium. Based on the experimental observation, a probable mechanism has been proposed. To see the anti‐cancer properties, we have studied concentration‐dependent cell viability assay of one compound on SiHa cell, a human cervical cancer cell line. The observed IC50 value was 23 μM.

Gamma‐papillomaviruses, though traditionally classified as cutaneotropic, actual tissue tropism is largely unexplored. This study aimed to evaluate the tissue‐specific prevalence of two novel‐HPV 223 and 225 in samples of oral mucosa and keratinized epithelium of varied skin parts from 226 female and male subjects, with or without neoplastic/dysplastic lesions in oral cavity or cervix. The gamma‐human papillomavirus (gamma‐HPV) 223 and 225 DNA presences were determined by polymerase chain reaction (PCR) ursing the HPV type‐specific primers and confirmed by Sanger sequencing. Viral load in the HPV 223 and HPV 225 positive samples were determined by absolute real‐time quantification method. Alpha‐HPV DNA prevalence was also checked in oral mucosa to ascertain coinfection status. Novel HPV 223 was present in 4.4% (10/226) oral mucosal samples of the study population; interestingly all were females with no prevalence in their corresponding skin swab samples. Whereas, the prevalence of HPV 225 was found both in the skin and oral mucosa of 28.2% (N = 37/131) female and 17.9% (N = 17/95) male participants. Alongside, HPV 223 viral load was found to be significantly higher (p = 0.02 < 0.05) in the oral mucosa of diseased participants, whereas, HPV 225 viral load was higher in the oral mucosa of normal participants. Our results suggest that gamma‐HPV 223 has its prevalence only in the oral mucosal epithelium, whereas, HPV 225 has its prevalence on both mucosal and keratinized skin epithelium, indicating its dual tropism nature.