Decellularized amniotic membrane hydrogel promotes mesenchymal stem cell differentiation into smooth muscle cells.

Previous studies showed that the bladder extracellular matrix (B-ECM) could increase the differentiation efficiency of mesenchymal cells into smooth muscle cells (SMC). This study investigates the potential of human amniotic membrane-derived hydrogel (HAM-hydrogel) as an alternative to xenogeneic B-ECM for the myogenic differentiation of the rabbit adipose tissue-derived MSC (AD-MSC). Decellularized human amniotic membrane (HAM) and sheep urinary bladder (SUB) were utilized to create pre-gel solutions for hydrogel formation. Rabbit AD-MSCs were cultured on SUB-hydrogel or HAM-hydrogel-coated plates supplemented with differentiation media containing myogenic growth factors (PDGF-BB and TGF-ß1). An uncoated plate served as the control. After 2 weeks, real-time qPCR, immunocytochemistry, flow cytometry, and western blot were employed to assess the expression of SMC-specific markers (MHC and α-SMA) at both protein and mRNA levels. Our decellularization protocol efficiently removed cell nuclei from the bladder and amniotic tissues, preserving key ECM components (collagen, mucopolysaccharides, and elastin) within the hydrogels. Compared to the control, the hydrogel-coated groups exhibited significantly upregulated expression of SMC markers (p ≤ .05). These findings suggest HAM-hydrogel as a promising xenogeneic-free alternative for bladder tissue engineering, potentially overcoming limitations associated with ethical concerns and contamination risks of xenogeneic materials.

The clinical impact of mRNA therapeutics in the treatment of cancers, infections, genetic disorders, and autoimmune diseases.

mRNA-based therapeutics have revolutionized medicine and the pharmaceutical industry. The recent progress in the optimization and formulation of mRNAs has led to the development of a new therapeutic platform with a broad range of applications. With a growing body of evidence supporting the use of mRNA-based drugs for precision medicine and personalized treatments, including cancer immunotherapy, genetic disorders, and autoimmune diseases, this emerging technology offers a rapidly expanding category of therapeutic options. Furthermore, the development and deployment of mRNA vaccines have facilitated a prompt and flexible response to medical emergencies, exemplified by the COVID-19 outbreak. The establishment of stable and safe mRNA molecules carried by efficient delivery systems is now available through recent advances in molecular biology and nanotechnology. This review aims to elucidate the advancements in the clinical applications of mRNAs for addressing significant health-related challenges such as cancer, autoimmune diseases, genetic disorders, and infections and provide insights into the efficacy and safety of mRNA therapeutics in recent clinical trials.

Mechanotransduction in tissue engineering: Insights into the interaction of stem cells with biomechanical cues.

Stem cells in their natural microenvironment are exposed to biochemical and biophysical cues emerging from the extracellular matrix (ECM) and neighboring cells. In particular, biomechanical forces modulate stem cell behavior, biological fate, and early developmental processes by sensing, interpreting, and responding through a series of biological processes known as mechanotransduction. Local structural changes in the ECM and mechanics are driven by reciprocal activation of the cell and the ECM itself, as the initial deposition of matrix proteins sequentially affects neighboring cells. Recent studies on stem cell mechanoregulation have provided insight into the importance of biomechanical signals on proper tissue regeneration and function and have shown that precise spatiotemporal control of these signals exists in stem cell niches. Against this background, the aim of this work is to review the current understanding of the molecular basis of mechanotransduction by analyzing how biomechanical forces are converted into biological responses via cellular signaling pathways. In addition, this work provides an overview of advanced strategies using stem cells and biomaterial scaffolds that enable precise spatial and temporal control of mechanical signals and offer great potential for the fields of tissue engineering and regenerative medicine will be presented.

Quercetin can be a more reliable treatment for metastatic prostate cancer than the localized disease: An in vitro study.

Quercetin is a plant flavonoid that has been recognized to have anti-inflammatory, antioxidant and anti-proliferative activities. This study aims to evaluate the inhibitory effects of quercetin against prostate malignancy in vitro and the underlying resistance mechanism. IC50 values of quercetin were determined by MTT assay. Annexin-V/PI staining was used to measure the rate of apoptosis. DNA cell cycle was analysed by PI staining method. Real-time PCR was performed to assess mRNA levels of OPN isoforms, VEGF isoforms, P53 and KLK2. Migration potential, proliferative capability and nucleus morphology of cells were evaluated by the scratch-wound assay, colony-forming assay and Hoechst staining, respectively. Quercetin significantly increased the apoptosis rate of PC-3 and LNCaP cell lines, arrested the cell cycle at the sub-G1/G1 phase, and reduced the migration potential and colony-forming capability. Moreover, upregulation of apoptosis-related genes and downregulation of genes involved in proliferation and angiogenesis was also observed. Although our results elucidated that quercetin has antitumor effects on PC-3 and LNCaP, for the first time, we showed that quercetin treatment causes alterations in the expression of OPN and VEGF isoforms, which are cancer-promoting modulators through various processes such as angiogenesis and drug-resistance. Prostate malignant cells can dodge the anti-carcinogenic properties of quercetin via modulation of OPN and VEGF isoforms in vitro. Therefore, quercetin acts as a double-edged sword in prostate cancer treatment.