AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer.

Castration resistant prostate cancer (CRPC) remains an incurable disease stage with ineffective treatments options. Here, the androgen receptor (AR) coactivators CBP/p300, which are histone acetyltransferases, were identified as critical mediators of DNA damage repair (DDR) to potentially enhance therapeutic targeting of CRPC. Key findings demonstrate that CBP/p300 expression increases with disease progression and selects for poor prognosis in metastatic disease. CBP/p300 bromodomain inhibition enhances response to standard of care therapeutics. Functional studies, CBP/p300 cistrome mapping, and transcriptome in CRPC revealed that CBP/p300 regulates DDR. Further mechanistic investigation showed that CBP/p300 attenuation via therapeutic targeting and genomic knockdown decreases homologous recombination (HR) factors in vitro, in vivo, and in human prostate cancer (PCa) tumors ex vivo. Similarly, CBP/p300 expression in human prostate tissue correlates with HR factors. Lastly, targeting CBP/p300 impacts HR-mediate repair and patient outcome. Collectively, these studies identify CBP/p300 as drivers of PCa tumorigenesis and lay the groundwork to optimize therapeutic strategies for advanced PCa via CBP/p300 inhibition, potentially in combination with AR-directed and DDR therapies.

Multi-functional copper oxide nanoparticles synthesized using Lagerstroemia indica leaf extracts and their applications.

Developing multifunctional nanomaterials through environmentally friendly and efficient approaches is a pivotal focus in nanotechnology. This study aimed to employ a biogenic method to synthesize multifunctional copper oxide nanoparticles (LI-CuO NPs) with diverse capabilities, including antibacterial, antioxidant, and seed priming properties, as well as photocatalytic organic dye degradation and wastewater treatment potentials using Lagerstroemia indica leaf extract. The synthesized LI-CuO NPs were extensively characterized using UV-vis spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform-infrared spectroscopy (FT-IR). The colloid displayed surface plasmon resonance peaks at 320 nm, characteristic of LI-CuO NPs. DLS analysis revealed an average particle size of 93.5 nm and a negative zeta potential of -20.3 mV. FTIR and XPS analyses demonstrated that LI-CuO NPs possessed abundant functional groups that acted as stabilizing agents. XRD analysis indicated pure crystalline and spherical LI-CuO NPs measuring 36 nm in size. Antibacterial tests exhibited significant differential activity of LI-CuO NPs against both gram-negative (Escherichia coli, Salmonella typhimurium) and gram-positive (Staphylococcus aureus and Listeria monocytogenes) bacteria. In antioxidant tests, the LI-CuO NPs demonstrated a remarkable radical scavenging activity of 97.6 % at a concentration of 400 µg mL-1. These nanoparticles were also found to enhance mustard seed germination at low concentrations. With a remarkable reusability, LI-CuO NPs exhibited excellent photocatalytic performance, with a degradation efficiency of 97.6 % at 150 µg/mL as well as a 95.6 % reduction in turbidity when applied to wastewater treatment. In conclusion, this study presents environmentally friendly method for the facile synthesis of LI-CuO NPs that could potentially offer promising applications in biomedicine, agriculture, and environmental remediation due to their multifunctional properties.

Green Synthesis of Novel Silver Nanoparticles Using Salvia blepharophylla and Salvia greggii: Antioxidant and Antidiabetic Potential and Effect on Foodborne Bacterial Pathogens.

In the face of evolving healthcare challenges, the utilization of silver nanoparticles (AgNPs) has emerged as a compelling solution due to their unique properties and versatile applications. The aim of this study was the synthesis and characterization of novel AgNPs (SB-AgNPs and SG-AgNPs, respectively) using Salvia blepharophylla and Salvia greggii leaf extracts and the evaluation of their antimicrobial, antioxidant, and antidiabetic activities. Several analytical instrumental techniques were utilized for the characterization of SB-AgNPs and SG-AgNPs, including UV-visible (UV-Vis) spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transmission infrared (FT-IR) spectroscopy, energy-dispersive X-ray analysis (EDX), and X-ray diffraction (XRD). FTIR analysis identified various functional groups in the leaf extracts and nanoparticles, suggesting the involvement of phytochemicals as reducing and stabilizing agents. High-resolution TEM images displayed predominantly spherical nanoparticles with average sizes of 52.4 nm for SB-AgNPs and 62.5 nm for SG-AgNPs. Both SB-AgNPs and SG-AgNPs demonstrated remarkable antimicrobial activity against Gram-positive bacteria Staphylococcus aureus and Listeria monocytogenes and Gram-negative bacteria Salmonella typhimurium and Escherichia coli. SB-AgNPs and SG-AgNPs also exhibited 90.2 ± 1.34% and 89.5 ± 1.5% DPPH scavenging and 86.5 ± 1.7% and 80.5 ± 1.2% α-amylase inhibition, respectively, at a concentration of 100 µg mL-1. Overall, AgNPs synthesized using S. blepharophylla and Salvia greggii leaf extracts may serve as potential candidates for antibacterial, antioxidant, and antidiabetic agents. Consequently, this study provides viable solutions to mitigate the current crisis of antibiotic resistance and to efficiently combat antimicrobial infections and Type 2 diabetes.