The Role of ERα and ERß in Castration-Resistant Prostate Cancer and Current Therapeutic Approaches.

Castration-resistant prostate cancer, or CRPC, is an aggressive stage of prostate cancer (PCa) in which PCa cells invade nearby or other parts of the body. When a patient with PCa goes through androgen deprivation therapy (ADT) and the cancer comes back or worsens, this is called CRPC. Instead of androgen-dependent signalling, recent studies show the involvement of the estrogen pathway through the regulation of estrogen receptor alpha (ERα) and estrogen receptor beta (ERß) in CRPC development. Reduced levels of testosterone due to ADT lead to low ERß functionality in inhibiting the proliferation of PCa cells. Additionally, ERα, which possesses androgen independence, continues to promote the proliferation of PCa cells. The functions of ERα and ERß in controlling PCa progression have been studied, but further research is needed to elucidate their roles in promoting CRPC. Finding new ways to treat the disease and stop it from becoming worse will require a clear understanding of the molecular processes that can lead to CRPC. The current review summarizes the underlying processes involving ERα and ERß in developing CRPC, including castration-resistant mechanisms after ADT and available medication modification in mitigating CRPC progression, with the goal of directing future research and treatment.

The Role of Anthocyanin in Modulating Diabetic Cardiovascular Disease and Its Potential to Be Developed as a Nutraceutical.

Cardiovascular disease (CVD) is directly linked to diabetes mellitus (DM), and its morbidity and mortality are rising at an alarming rate. Individuals with DM experience significantly worse clinical outcomes due to heart failure as a CVD consequence than non-diabetic patients. Hyperglycemia is the main culprit that triggers the activation of oxidative damage, inflammation, fibrosis, and apoptosis pathways that aggravate diabetic CVD progression. In recent years, the development of phytochemical-based nutraceutical products for diabetic treatment has risen due to their therapeutic properties. Anthocyanin, which can be found in various types of plants, has been proposed for preventing and treating various diseases, and has elicited excellent antioxidative, anti-inflammation, anti-fibrosis, and anti-apoptosis effects. In preclinical and clinical studies, plants rich in anthocyanin have been reported to attenuate diabetic CVD. Therefore, the development of anthocyanin as a nutraceutical in managing diabetic CVD is in demand. In this review, we unveil the role of anthocyanin in modulating diabetic CVD, and its potential to be developed as a nutraceutical for a therapeutic strategy in managing CVD associated with DM.

Knowledge Gap in Understanding the Steroidogenic Acute Regulatory Protein Regulation in Steroidogenesis Following Exposure to Bisphenol A and Its Analogues.

The use of bisphenols has become extremely common in our daily lives. Due to the extensive toxic effects of Bisphenol A (BPA), the industry has replaced this endocrine-disrupting chemical (EDC) with its analogues, which have been proven to decrease testosterone levels via several mechanisms, including targeting the steroidogenic acute regulatory (StAR) protein. However, when exposed to BPA and its analogues, the specific mechanism that emerges to target StAR protein regulations remains uncertain. Hence, this review discusses the effects of BPA and its analogues in StAR protein regulation by targeting cAMP-PKA, PLC-PKC, EGFR-MAPK/ERK and Ca2+-Nur77. BPA and its analogues mainly lead to decreased LH in blood and increased ERK expression and Ca2+ influx, with no relationship with the StAR protein regulation in testicular steroidogenesis. Furthermore, the involvement of the cAMP-PKA, PLC-PKC, and Nur77 molecules in StAR regulation in Leydig cells exposed to BPA and its analogues remains questionable. In conclusion, although BPA and its analogues have been found to disrupt the StAR protein, the evidence in connecting the signaling pathways with the StAR regulations in testicular steroidogenesis is still lacking, and more research is needed to draw a solid conclusion.

The Potential Role of Flavonoids in Ameliorating Diabetic Cardiomyopathy via Alleviation of Cardiac Oxidative Stress, Inflammation and Apoptosis.

Diabetic cardiomyopathy is one of the major mortality risk factors among diabetic patients worldwide. It has been established that most of the cardiac structural and functional alterations in the diabetic cardiomyopathy condition resulted from the hyperglycemia-induced persistent oxidative stress in the heart, resulting in the maladaptive responses of inflammation and apoptosis. Flavonoids, the most abundant phytochemical in plants, have been reported to exhibit diverse therapeutic potential in medicine and other biological activities. Flavonoids have been widely studied for their effects in protecting the heart against diabetes-induced cardiomyopathy. The potential of flavonoids in alleviating diabetic cardiomyopathy is mainly related with their remedial actions as anti-hyperglycemic, antioxidant, anti-inflammatory, and anti-apoptotic agents. In this review, we summarize the latest findings of flavonoid treatments on diabetic cardiomyopathy as well as elucidating the mechanisms involved.

Lineage-related and particle size-dependent cytotoxicity of chitosan nanoparticles on mouse bone marrow-derived hematopoietic stem and progenitor cells.

Chitosan nanoparticles (CSNPs) have potential applications in stem cell research. In this study, ex vivo cytotoxicity of CSNPs on mouse bone marrow-derived (MBMCs) hematopoietic stem and progenitor cells (HSPCs) was determined. MBMCs were exposed to CSNPs of different particle sizes at various concentrations for up to 72 h. Cytotoxicity effect of CSNPs on MBMCs was determined using MTT, Live/Dead Viability/Cytotoxicity assays and flow cytometry analysis of surface antigens on HSCs (Sca-1(+)), myeloid-committed progenitors (CD11b(+), Gr-1(+)), and lymphoid-committed progenitors (CD45(+), CD3e(+)). At 24 h incubation, MBMCs' viability was not affected by CSNPs. At 48 and 72 h, significant reduction was detected at higher CSNPs concentrations. Small CSNPs (200 nm) significantly reduced MBMCs' viability while medium-sized particle (∼400 nm) selectively promoted MBMCs growth. Surface antigen assessment demonstrated lineage-dependent effect. Significant decrease in Sca-1(+) cells percentage was observed for medium-sized particle at the lowest CSNPs concentration. Meanwhile, reduction of CD11b(+) and Gr-1(+) cells percentage was detected at high and intermediate concentrations of medium-sized and large CSNPs. Percentage of CD45(+) and CD3e(+) cells along with ROS levels were not significantly affected by CSNPs. In conclusion, medium-sized and large CSNPs were relatively non-toxic at lower concentrations. However, further investigations are necessary for therapeutic applications.