Endothelial-to-mesenchymal transition: New insights into vascular calcification.

With the continuous progress of atherosclerosis research, the significant pathological change of it--vascular calcification (VC), gains increasing attention. In recent years, numerous studies have demonstrated that it is an independent predictor of death risk of cardiovascular disease, and it has a strong correlation with poor clinical prognosis. As the world's population continues to age, the occurrence of VC is expected to reach its highest point in the near future. Therefore, it is essential to investigate ways to prevent or even reverse this process for clinical purposes. Endothelial-to-mesenchymal transition (EndMT) describes the progressive differentiation of endothelial cells into mesenchymal stem cells (MSCs) under various stimuli and acquisition of pluripotent cell characteristics. More and more studies show that EndMT plays a vital role in various cardiovascular diseases, including atherosclerosis, vascular calcification and heart valvular disease. EndMT is also involved in the formation and progression of VC. This review vividly describes the history, characteristics of EndMT and how it affects the endothelial cell process, then focuses on the relationship between vascular endothelium, EndMT, amino acid metabolism, and vascular calcification. Finally, it overviews the signal pathway of EndMT and drugs targeting EndMT, hoping to provide new ideas and a theoretical basis for studying potential therapeutic targets of VC.

Small extracellular vesicles isolation and separation: Current techniques, pending questions and clinical applications.

Extracellular vesicles, especially small extracellular vesicles (sEVs) are now accepted as important messengers in cell-to-cell communication and as a promising drug delivery platform. They are involved in nearly all physiological and pathological processes and are involved in disease diagnosis and therapy. However, their heterogeneity of physicochemical properties and functions is not fully understood, which hinders further clinical applications. To obtain highly bioactive sEVs with both high yield and purity, will certainly facilitate their future study and application. This review informs up-to-date research on frequently-used and cutting-edge technologies of sEVs isolation and makes a deep comparison and analysis of different methods, including their advantages, limitations and applications. Pending questions about the inherent property of these small vesicles as well as isolation strategies are discussed. Additionally, an overview of their applications in disease diagnosis and treatment, including some of the on-going clinical trials, are also reviewed.

3,3'-Diindolylmethane Promotes Gastric Cancer Progression via ß-TrCP-Mediated NF-κB Activation in Gastric Cancer-Derived MSCs.

Gastric cancer is a malignant tumor characterized by high morbidity and invasion. Surgery combined with chemo-radiotherapy is the most common treatment for gastric cancer, while multiple drug resistance always results in treatment failure. Once the anti-tumor drugs enter the tumor foci, tumor cells as well as those found in the microenvironment are affected. However, the effects of drugs on tumor microenvironment (TME) are easily overlooked. In this study, we investigated the effects of the anti-cancer drug 3,3'-diindolylmethane (DIM) on gastric cancer-derived mesenchymal stem cells (GC-MSCs) and their subsequent impact on cancer progression. Surprisingly, we found that the therapeutic concentration of DIM upregulated the expression level of tumor-related factors such as CCL-2, IL-6, and IL-8 in GC-MSCs. The conditioned medium of DIM-treated GC-MSCs promoted the proliferation, invasion, and migration of gastric cancer cells in vitro and tumor growth in vivo. Mechanistically, DIM enhanced the expression of ß-TrCP, an E3 ubiquitin ligase leading to IκBα degradation and NF-κB activation in GC-MSCs. The ß-TrCP knockdown partially eliminated positive results caused by DIM. Our results showed that the therapeutic dosage of DIM induced cell death in cancer cells, while enhancing MSC paracrine functions in the stroma to offset the original DIM effect on cancer cells. These findings provide a new mechanism of anti-cancer drug resistance and remind us to adjust the chemotherapeutic scheme by combining the anti-cancer drug with an appropriate signaling pathway inhibitor to block the side effects of drug on targeted TME cells.