Research and application of hydrogel-encapsulated mesenchymal stem cells in the treatment of myocardial infarction.

Myocardial infarction (MI) stands out as a highly lethal disease that poses a significant threat to global health. Worldwide, heart failure resulting from MI remains a leading cause of human mortality. Mesenchymal stem cell (MSC) therapy has emerged as a promising therapeutic approach, leveraging its intrinsic healing properties. Nevertheless, pervasive issues, including a low cell retention rate, suboptimal survival rate, and incomplete differentiation of MSCs, present formidable challenges for further research. The introduction and advancement of biomaterials have offered a novel avenue for the exploration of MSC therapy in MI, marking considerable progress thus far. Notably, hydrogels, among the representative biomaterials, have garnered extensive attention within the biomedical field. This review delves into recent advancements, specifically focusing on the application of hydrogels to augment MSC therapy for cardiac tissue regeneration in MI.

Histone ubiquitination-related gene CUL4B promotes lung adenocarcinoma progression and cisplatin resistance.

Background: The role of the histone ubiquitination-related gene in the cisplatin resistance of lung adenocarcinoma (LUAD) remains an intricate subject. Methods: We accessed transcriptome data of both wild type and cisplatin-resistant cells from the GSE108214 dataset, and garnered transcriptome and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) database. Utilizing the R software, we analyzed these public datasets in depth. Real-time Quantitative PCR (qPCR) was used to detect the RNA level of CUL4B. Effect of CUL4B on cell proliferation was evaluated using CCK8 and colony formation assay. Effect of CUL4B on cell invasion was evaluated using transwell assay. Cisplatin sensitivity was evaluated by calculating IC50. Results: Our analysis shed light on the significance of the histone ubiquitination-related gene, CUL4B, in relation to cisplatin resistance and the overall survival rates of LUAD patients. Notably, CUL4B was found to be overexpressed in both lung cancer tissues and cells. Meanwhile, in vitro experiments indicated can CUL4B significantly promote the proliferation, invasion and migration of lung cancer cells. Furthermore, suppressing CUL4B expression led to a noticeable reduction in the IC50 value of cisplatin in lung cancer cells. A deep dive into biological enrichment analysis revealed that among patients exhibiting high CUL4B expression, there was a pronounced activation of the G2M checkpoint and the PI3K/AKT/mTOR signaling pathways. Immune microenvironment analysis has revealed that patients with elevated CUL4B expression may exhibit increased infiltration of M2 macrophages, coupled with a reduced infiltration of CD8+ T cells and activated NK cells. Notably, we observed higher CUL4B expression among those who responded positively to immunotherapy. Conclusion: These findings underscore the significance of CUL4B in the resistance to cisplatin in lung cancer, highlighting its potential as a therapeutic target.

Elastic and Conductive Melanin/Poly(Vinyl Alcohol) Composite Hydrogel for Enhancing Repair Effect on Myocardial Infarction.

Heart failure caused by acute myocardial infarction (MI) still remains the main cause of death worldwide. Development of conductive hydrogels provided a promising approach for the treatment of myocardial infarction. However, the therapeutic potential of these hydrogels is still limited by material toxicity or low conductivity. The latter directly affects the coupling and the propagation of electrical signals between cells. Here, a functional conductive hydrogel by combining hydrophilic and biocompatible poly(vinyl alcohol) (PVA) with conductive melanin nanoparticles under physical crosslinking conditions is prepared. The composite hydrogels prepared by a facile fabrication process of five freeze/thaw cycles possessed satisfying mechanical properties and conductivity close to those of the natural heart. The physical properties and biocompatibility are evaluated in vitro experiments, showing that the introduction of melanin particles successfully improved the elasticity, conductivity, and cell adhesion of PVA hydrogel. In vivo, the composite hydrogels can enhance the cardiac repair effect by reducing MI area, slowing down ventricular wall thinning, and promoting the vascularization of infarct area in MI rat model. It is believed that the melanin/PVA composite hydrogel may be a suitable candidate material for MI repair.