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Breast cancer is the most common cancer among women worldwide, causing 15% of cancer-related deaths among women. Breast cancer incidence rate is increasing in most countries. In Saudi Arabia, breast cancer constitutes nearly 22% of the newly diagnosed cancer cases in women. Breast cancer incidence in the women population of Saudi Arabia is 25.9%, with 18.2% mortality. In this study, targeted sequencing of 164 selected genes was performed on germline and somatic DNA derived from the blood and tissue samples of 50 breast cancer patients using customized panel on Ion torrent platform. This study focused on the identification of genetic variations of different cancer-causing genes, raising the hope for identification of personalized prognosis. After final filtration and validation, we found protein-truncating, non-synonymous missense, and splice site mutations in the known susceptibility genes for breast cancer. We identified a total of 14 point mutations and one deletion in BRCA1 , BRCA2 , and RAD50 genes from the BRCA panel analysis of breast cancer samples. In the customized panel analysis, we identified 37 potential mutations in 25 breast cancer risk associated genes. Out of these, most mutations were observed in TP53. After filtration, we observed 7 mutations in TP53 genes (n = 7:- one stop gain (p.R81X), four non-synonymous (p.R81X, p.Y88C, p.R141H, and p.V25D), and two deletions (c.59delC and c.327delC)). Among the mutations detected in our study, TP53 (p.R81X), VHL (p.E52X), and BRCA2 (p.K3326X) mutations, which lead to an aberrant transcript with a premature stop codon, were reported for the first time in breast cancer patients from Saudi Arabia. Our study will help in identifying the damaging mutations and predisposing genes in Saudi breast cancer patients. [ABSTRACT FROM AUTHOR]

Severe pathogen infections, such as Monkeypox disease caused by the Monkeypox virus, easily spread in different animals and then into humans. There is an urge for novel therapeutic options, such as medicine/vaccine development to control it. Therefore, we designed Pinocembrin derivatives and performed in silico analysis such as molecular docking by PyRx software, molecular dynamics (MD) simulations at 100 ns, binding free energy estimation by AMBER20 software, ADMET profile, and Pass prediction. Optimal results were observed for two derivatives (07 and 11), exhibiting interactions with key residues of the selected protein. These interactions were substantiated by a range of structural and energetic parameters, including binding energies, solvation-free energy models, dynamic fluctuations, hydrogen bonding, and solvent accessibility. Notably, ligands 07 and 11 displayed exceptional binding affinities of −10.3 kcal/mol and −9.6 kcal/mol, respectively. RMSD value presented minor abruptions of about 1.2 to 1.3 Å and superimposed structures of selected derivatives complexes with Monkeypox target protein at 0 ns and 100 ns presented minor fluctuation in the native and bounded conformation. Slight instability is noted from the peaks in graphs of RMSD, RMSF, hydrogen bonds (HBs), beta factor (BF), and solvent-accessible surface area (SASA). Based on promising results, we proposed that Pinocembrin derivatives may serve as novel therapeutic agents against Monkeypox infections. Therefore, strongly advocate for further experimental validation through chemical laboratory testing. Such endeavors could pave the way for the development of effective treatments to mitigate the impact of Monkey-Pox disease. [ABSTRACT FROM AUTHOR]