Embryonic microenvironment suppresses YY1 and YY1-related genes in prostate cancer stem cells.

Yin yang 1 (YY1), a transcription factor, plays crucial roles in cell fate specification, differentiation, and pluripotency during embryonic development. It is also involved in tumorigenesis, drug resistance, metastasis, and relapse caused by cancer stem cells (CSCs), particularly in prostate cancer (PCa). Targeting YY1 could potentially eliminate prostate CSCs (PCSCs) and provide novel therapeutic approaches. PCa tissues often exhibit elevated YY1 expression levels, especially in high-grade cases. Notably, high-grade PCa tissues from 58 PCa patients and CD133high/CD44high PCSCs isolated from DU145 PCa cell line by FACS both showed significantly increased YY1 expression as observed through immunofluorescence staining, respectively. To investigate the embryonic microenvironment impact on YY1 expression in CSC populations, firstly PCSCs were microinjected into the inner cell mass of blastocysts and then PCSCs were co-cultured with blastocysts. Next Generation Sequencing was used to analyze alterations in YY1 and related gene expressions. Interestingly, exposure to the embryonic microenvironment significantly reduced the expressions of YY1, YY2, and other relevant genes in PCSCs. These findings emphasize the tumor-suppressing effects of the embryonic environment by downregulating YY1 and YY1-related genes in PCSCs, thus providing promising strategies for PCa therapy. Through elucidating the mechanisms involved in embryonic reprogramming and its effects on YY1 expression, this research offers opportunities for further investigation into focused therapies directed against PCSCs, therefore enhancing the outcomes of PCa therapy. As a result, PCa tumors may benefit from YY1 and associated genes as a novel therapeutic target.

Splicing variants of versican in CD133+/CD44+ prostate cancer stem cells.

A cancer mass is composed of a heterogeneous group of cells, a small part of which constitutes the cancer stem cells since they are less differentiated and have a high capacity to develop cancer. Versican is an extracellular matrix protein located in many human tissues. The mRNA of versican has been shown to have "splicing patterns" as detected by RT-PCR, northern blot analysis, and cDNA sequencing. Based on this knowledge this study aims to reveal the splice variants of versican molecules, which are thought to be involved in the pathogenesis of the DU-145 human prostatic carcinoma cell line and prostatic cancer stem cells isolated from this cell line. In this study, RWPE-1 normal prostatic and DU-145 human prostate cancer cell lines have been used. Prostatic cancer stem cells and the remaining group of non-prostatic-cancer stem cells (bulk population) were isolated according to their CD133+/CD44+. RNA was isolated in all groups, and sequence analysis was accomplished for splicing variants by Illumina NextSeq 500 sequencing system. The results were analyzed by bioinformatic evaluation. As five isoforms of the versican gene in the differential transcript expression are analyzed, it was observed that a significant change was only found in the isoforms Versican 0 and Versican 1. In this study, we explored the function of this molecule which we think to be effective in cancer progression, and suggested that more valuable results can be obtained after the accomplishment of in vivo experiments.

LDH-A Inhibitor as a Remedy to Potentiate the Anticancer Effect of Docetaxel in Prostate Cancer.

Increased LDH-A activity promotes tumor growth, migration, invasion, and metastasis. This study aimed to investigate the effects of the combination of LDH-A inhibitor and Docetaxel on apoptosis and epithelial-mesenchymal transition (EMT) in the murine prostate cancer (PCa) model. The prostate cancer murine model was developed subcutaneously in 50 male B57CL/6 mice using the Tramp-C2 prostate cancer cell line. From the tumor tissue samples, apoptosis analysis was performed using TUNEL staining, and EMT was investigated using western blot and qPCR. Hematoxylin-eosin staining (HE) and Periodic acid-Schiff staining were used to histopathologically examine liver and kidney tissues. Lactate levels revealed that the Warburg effect was reversed with the LDH-A inhibitor. Both serum and tumor tissue apoptosis increased, and tumor sizes reduced in PCa+LDH-A inhibitor + Docetaxel treatment groups (p<0.05). The combination of LDH-A inhibitor and Docetaxel inhibited EMT mechanism by causing a decrease in Snail, Slug, Twist, and HIF-1α expressions as well as a decrease in N-cadherin and an increase in E-cadherin levels. Reprogramming glucose metabolism with an LDH-A inhibitor can increase the effectiveness of Docetaxel on apoptosis and metastasis mechanisms in PCa.

Design and characterization of nanocarriers loaded with Levofloxacin for enhanced antimicrobial activity; physicochemical properties, in vitro release and oral acute toxicity

Inorganic and carbon based nanomaterials are widely used against several diseases, such as cancer, autoimmune diseases as well as fungi and bacteria colonization. In this work, Santa Barbara Amorphous mesoporous silica (SBA), Halloysite Nanotubes (HNTs) and Multiwalled Carbon Nanotubes (CNTs) were loaded with fluoroquinolone Levofloxacin (LVF) to be applied as antimicrobial agents. The prepared via adsorption nanocarriers were characterized by Fourier-Transformed Spectroscopy, Scanning Electron Microscopy as well as High Pressure liquid Chromatography. In vitro release studies were carried out using Simulated Body Fluid at 37oC and data analyzed by various kinetic models showing slow dissolution over 12-24 hours. Antimicrobial studies showed improved antibacterial activity against Escherichia coli, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, and Staphylococcus epidermidis compared to neat nanomaterials. CNTs were found to be the most promising candidates for LVF delivery and they were chosen to be further studied for their acute oral toxicity and histopathological examination using C57/Black mice. Histological examination depicted that drug loading did not affect mice organs morphology as well as hepatocyte degeneration, central vein degeneration and parenchymal necrosis scores. To conclude, the prepared nanomaterials present significant characteristics and can act as antimicrobial drug carriers; CNTs found to be safe candidates when orally fed to mice.