Search

Abstract The purpose of the current study was to analyze and validate the existing gap in knowledge, by conducting a differential expression analysis and validation of NEK6, NEK7, and NEK9 in breast, cervical, and glioblastoma cancer and targeting these proteins through development of novel site specific inhibitor with favorable pharmacokinetic and safety profile, using open-source databases. The analysis revealed that the targeted kinases were overexpressed in all three types of cancer. Their expression was significantly linked to overall survival rates, which suggests that they play a major role in the development and progression of these cancers. After, having the prognostic importance of These findings provided a rationale for synthesizing novel compound i.e., dimethyl 2,2’-((methylenebis(2-(2H-benzo[d][1,2,3]triazol-2-yl)-4-(2,4,4-trimethylpentan-2-yl)-6,1phenylene))bis(oxy))diacetate (TAJ4)), capable of effectively targeting these proteins using in-vitro cytotoxicity assays and comprehensive computational approaches. Then the inhibitory potential of TAJ4 was evaluated against cell lines of the respective cancers (HeLa cells, MCF-7 cells, and Vero cells). The growth inhibitory values (GI50) suggested that TAJ4 exhibited strong inhibitory potential towards MCF-7 cells (GI50 = 3.18 ± 0.11 µM) in comparison to the HeLa cell line (GI50 = 8.12 ± 0.43 µM), surpassing that of standard drugs. Furthermore, in-silico investigations, including density functional theory (DFT) calculations and molecular docking studies, revealed a substantial reactivity profile of TAJ4, with promising molecular interactions against NEK7, NEK9, TP53, NF-KAPPA-B, and caspase-3 proteins. Further investigation using in-vitro and in-vivo approaches is recommended to fully establish the therapeutic efficacy and safety profile of TAJ4.

Abstract Oropharyngeal cancer, a subset of head and neck cancer, is increasingly recognized as a unique clinical entity primarily influenced by high-risk human papillomavirus (HPV) infections, particularly HPV-16. This review delves into the viral life cycle of HPV-16 and its interactions with host cells, with a specific focus on the crucial roles played by the viral oncoproteins E6 and E7. These oncoproteins drive cellular proliferation by targeting critical tumor suppressor proteins like p53 and Rb, resulting in uncontrolled cell growth and genomic instability. Furthermore, the significance of epigenetic modifications induced by HPV-16 and their implications is important for cancer progression. This comprehensive review provides valuable insights into the intricate molecular landscape of HPV-induced oropharyngeal cancer, shedding light on the development of targeted therapies and preventive strategies for this emerging global health concern. Video Abstract

Abstract Background Pneumocystis pneumonia (PCP) is a fatal infectious disease caused by Pneumocystis jirovecii (PJP). The major factor relevant to morbidity and mortality seems to be the host inflammatory reaction. The objective of this study was to evaluate the role of IL-2, IL-4, IL-10, and IL-13 cytokine mRNA expression among suspected P. jirovecii infection. Methods This was a cross-sectional analytical study undertaken in Aseer region, Saudi Arabia. One hundred suspected PCP cases and 100 healthy controls were included in the study. Basic clinical manifestations, radiological findings, microbiological and immunological findings were extracted from the hospital records from January 2019 to August 2019, Pneumocystis detection was done by immune-fluorescent staining (IFAT, Gomorimethanamine silver staining (GMSS), Giemsa staining, Toluidine blue O (TBO), and Pneumocystis RT-PCR. Results Increased more than 5 fold, 3 fold, 4 fold, and 7 fold of IL-2, IL-4, IL-10, and IL-13 mRNA expression were observed in PCP cases compared to controls. Higher expression of IL-2 mRNA was connected with crept, wheezing and chest X-ray findings like central perihilar infiltrate, patchy infiltrate, consolidation, hilar lymphadenopathy, pneumothorax, pleural effusion which showed higher expression compared to counterpart (p