Gum acacia PEG iron oxide nanocomposite (GA-PEG-IONC) induced pharmacotherapeutic activity on the Las R gene expression of Pseudomonas aeruginosa and HOXB13 expression of prostate cancer (Pc 3) cell line. A green therapeutic approach of molecular mechanism inhibition.

Among the diverse nanomaterials, polymer-based nanocomposites are gained more attention due to their high efficacy, target biological activities, biodegradability and biocompatibility-gum acacia (GA) - a polymer obtained from acacia trees-is considering the multifunctional nanocomposite synthesis. Distinctive Physico-chemical and biocompatibility properties of gum acacia are utilised to prepare a highly stable, biologically active, eco-friendly Nanocomposite. In this current investigation, gum acacia - poly ethylene glycol grafted iron oxide nanocomposite (GA-PEG-IONC) was synthesised by in situ green science principles. The synthesised Nanocomposite was evaluated against the molecular mechanism of urinary tract pathogenic bacterial strains and prostate cancer cells (Pc 3). Nanocomposite prepared in this examination exhibited notable structural, functional stability with nanoarchitecture which was affirmed by Fourier transform infrared spectroscopy (FTIR), electron microscopic studies, atomic force microscopy (AFM), vibrating sample magnetometric analysis (VSM) and X-ray diffraction (XRD), Synthesised Nanocomposite brought about notable antibacterial activity against urinary tract pathogenic strains by recording potential inhibitory effect on the expression of Las R gene. Inhibition of Las R gene expression reduced notable effect on biofilm development. Anticancer activity against prostate cancer cells (Pc3) was investigated by measurement of HOXB13 gene expression level. Inhibition of HOXB13 gene expression by the IONC brought about structural, functional changes. HOXB13 gene expression inhibition reveals a remarkable cytotoxic effect by recording decreased cell viability. Morphometric analysis by phase-contrast and DAPI fluorescence staining demonstrates that the Nanocomposite prompted cell morphology anomalies or apoptotic changes. Nanocomposite treatment brought about a good sign of Apoptosis by recording enhanced caspase 3 and 9 activities, DNA fragmentation and elevated reactive oxygen species generation (ROS). Hemocompatibility studies were carried out to determine the biocompatibility of the Nanocomposite. Spectrophotometric estimation of plasma haemoglobin, microscopic examination of whole blood cells shows the Nanocomposite was not inciting any indication of toxicity. These findings infer that IONC synthesised in the present study is the promising contender for a broad scope of biomedical applications, especially as an antibacterial and anticancer agent.

Familial prostate cancer.

Prostate cancer is the most commonly diagnosed cancer among men in the United States as well as most Western countries. A significant proportion of men report having a positive family history of prostate cancer in a first-degree relative (father, brother, son), which is important in that family history is one of the only established risk factors for the disease and plays a role in decision-making for prostate cancer screening. Familial aggregation of prostate cancer is considered a surrogate marker of genetic susceptibility to developing the disease, but shared environment cannot be excluded as an explanation for clustering of cases among family members. Prostate cancer is both a clinically and genetically heterogeneous disease with inherited factors predicted to account for 40%-50% of cases, comprised of both rare highly to moderately penetrant gene variants, as well as common genetic variants of low penetrance. Most notably, HOXB13 and BRCA2 mutations have been consistently shown to increase prostate cancer risk, and are more commonly observed among patients diagnosed with early-onset disease. A recurrent mutation in HOXB13 has been shown to predispose to hereditary prostate cancer (HPC), and BRCA2 mutations to hereditary breast and ovarian cancer (HBOC). Genome-wide association studies (GWAS) have also identified approximately 100 loci that associate with modest (odds ratios <2.0) increases in prostate cancer risk, only some of which have been replicated in subsequent studies. Despite these efforts, genetic testing in prostate cancer lags behind other common tumors like breast and colorectal cancer. To date, National Comprehensive Cancer Network (NCCN) guidelines have highly selective criteria for BRCA1/2 testing for men with prostate cancer based on personal history and/or specific family cancer history. Tumor sequencing is also leading to the identification of germline mutations in prostate cancer patients, informing the scope of inheritance. Advances in genetic testing for inherited and familial prostate cancer (FPC) are needed to inform personalized cancer risk screening and treatment approaches.