Cangzhou Central Hospital

Traditional biological scaffolds for vaginal reconstruction often fail to restore the physiological bilayered structure of vaginal tissue, leading to post-operative complications such as contraction, stenosis, and fibrosis. To address this, we developed a biomimetic bilayered vaginal scaffold using decellularized porcine vaginal extracellular matrix (vECM), gelatin methacryloyl (GelMA), and silk fibroin (SF) hydrogels. The optimized bioink (vECM/GelMA/SF) was characterized via SEM, rheology, FTIR, swelling tests, and H&E staining, confirming its morphology, stability, and biocompatibility. Rabbit bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured, then directionally induced to differentiate into epithelial cells and smooth muscle cells. The differentiated cells were spatially loaded onto the inner and outer layers of the biomimetic scaffold for vaginal reconstruction. Following transplantation into rabbit vaginal defects, the scaffold mediated structural and functional restoration of vaginal tissue. Histological analyses at 12 weeks post-implantation confirmed: regeneration of mature stratified epithelium, organization of muscular bundles, and absence of complications including contraction, stenosis, or fibrosis. The uniqueness of this study lies in the first application of directionally differentiated BMSCs for vaginal reconstruction was synergistically combined with a bilayered 3D-printed architecture mimicking native vaginal stratification, enabling stem cell-driven regeneration of both epithelial and muscular tissues. This integrated approach achieved functional restoration of vaginal defects through precise spatial organization of differentiated cells within biomimetic layers.

Renal fibrosis is the core process in the progression of chronic kidney disease (CKD), and its irreversibility leads to end-stage renal disease. Recent studies have shown that metabolic reprogramming, particularly glycolytic reprogramming in renal tubular epithelial cells, is a key mechanism fuels fibrosis, presenting a significant metabolic paradox: short-term adaptive compensation (e.g., enhanced glycolysis) transforms into long-term pathological damage. This review systematically elaborates on the molecular mechanisms of glycolytic reprogramming: 1. FOXK1 forms transcriptional condensates through liquid-liquid phase separation (LLPS) to activate the expression of glycolytic genes, with genetic disruption attenuating fibrosis progression by 48 % (p < 0.01); 2. Pyruvate carboxylase (PC) deficiency triggers a vicious cycle of mitochondrial damage and glycolytic shift, evidenced by a 50 % reduction in PC expression in human fibrotic kidneys (p < 0.001) and a 70 % decrease in basal oxygen consumption rate in PC-knockout models; 3. Epigenetic regulation by metabolic enzymes (e.g., lactylation modification and PKM2 nuclear translocation) forms positive feedback pathways. Based on the above mechanisms, targeted intervention strategies are proposed: inhibiting glycolytic rate-limiting enzymes (HK2, LDHA), repairing mitochondrial function (antioxidation/kinetic regulation), and developing gene/nanotechnology (CRISPR editing, mitochondria-targeted carriers). Finally, current challenges are pointed out, including the spatiotemporal dynamic analysis of LLPS, bottlenecks in kidney-targeted delivery, and the potential of combined immunometabolic therapy, providing a theoretical basis for the development of new anti-fibrotic drugs.

Bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH) is extensively utilized as an alternative to traditional options like polybrominated diphenyl ethers (PBDEs). TBPH is a ubiquitous environmental contaminant, having been detected in a wide range of environmental media, biota, and human tissues, raising concerns about its potential risks to ecological systems and human health. Considering the significant association between environmental toxins and lung cancer, assessing the impact of TBPH on lung cancer is essential. This study utilized lung cancer cells as in vitro model to evaluate the effects of TBPH. Our findings indicate that TBPH enhances lung cancer cell proliferation, as determined by CCK-8 and EdU assays. Further investigations revealed that TBPH facilitates lung cancer progression by activating the mTORC1 pathway, as confirmed by indirect immunofluorescence and Western blot analyses. Additionally, TBPH enhances lipid synthesis in lung cancer cells, altering their lipid metabolism, which may contribute to lung cancer development. On the contrary, we also evaluated the toxicological effects of TBPH on lung tissues and cells. TBPH exposure showed a range of toxicological effects on lung epithelial cells and lung tissues. TBPH exposure induces pyroptosis in lung cells. In summary, our findings suggest that low levels of TBPH promote tumor cell growth, However, TBPH exhibited toxicological effects in lung epithelial cells, highlighting its adverse impact on pulmonary toxicity.