Coumarins improved type 2 diabetes induced by high-fat diet and streptozotocin in mice via antioxidation.

Coumarins extensively exist in plants and are utilized against diabetes in some folk medicines. Recent studies have demonstrated that oxidative stress plays a crucial role in the etiology and pathogenesis of diabetes mellitus. We investigated the antioxidant ability of 3 coumarins (osthole, esculin, and fraxetin) in type 2 diabetes. After being fed a high-fat diet, ICR mice were exposed to low doses of streptozotocin and then treated with experimental coumarins for 5 weeks. We found osthole, esculin, and metformin significantly lowered fasting blood glucose, HOMA-IR, and 3 blood lipids (total cholesterol, total triglyceride, free fatty acids), and increased insulin levels, while fraxetin only enhanced insulin levels and lessened free fatty acids. Both osthole and esculin had antioxidative effects in pancreas through elevating the activities of glutathione peroxidase, catalase, and superoxide dismutase; fraxetin, however, merely heightened catalase activity. By contrast, 3 coumarins significantly increased those antioxidase activities in liver. Hematoxylin and eosin staining revealed 3 coumarins, especially osthole, attenuated cellular derangement, blurry fringes of hepatic sinusoid and extensive vacuolization due to hepatocellular lipid accumulation, and lessened inflammatory infiltration in pancreas. The glomerular and islet structure of diabetic mice were improved, with reduced mesangial matrix and glomerular basement membrane thickening. Therefore, our study supports that coumarins could be promising candidates against type 2 diabetes through antioxidative mechanisms.

Red blood cells in biology and translational medicine: natural vehicle inspires new biomedical applications.

Red blood cells (RBCs) are the most abundant cell type in the blood, and play a critical role in oxygen transport. With the development of nanobiotechnology and synthetic biology, scientists have found multiple ways to take advantage of the characteristics of RBCs, such as their long circulation time, to construct universal RBCs, develop drug delivery systems, and transform cell therapies for cancer and other diseases. This article reviews the component and aging mystery of RBCs, the methods for the applied universal RBCs, and the application prospects of RBCs, such as the engineering modification of RBCs used in cytopharmaceuticals for drug delivery and immunotherapy. Finally, we summarize some perspectives on the biological features of RBCs and provide further insights into translational medicine.

Surface-Anchored Nanogel Coating Endows Stem Cells with Stress Resistance and Reparative Potency via Turning Down the Cytokine-Receptor Binding Pathways.

Stem cell-based therapy has great potential in regenerative medicine. However, the survival and engraftment rates of transplanted stem cells in disease regions are poor and limit the effectiveness of cell therapy due to the fragility of stem cells. Here, an approach involving a single-cell coating of surface-anchored nanogel to regulate stem cell fate with anti-apoptosis capacity in the hypoxic and ischemic environment of infarcted hearts is developed for the first time. A polysialic acid-based system is used to anchor microbial transglutaminase to the external surface of the cell membrane, where it catalyzes the crosslinking of gelatin. The single-cell coating with surface-anchored nanogel endows mesenchymal stem cells (MSCs) with stress resistance by blocking the activity of apoptotic cytokines including the binding of tumor necrosis factor α (TNFα) to tumor necrosis factor receptor, which in turn maintains mitochondrial integrity, function and protects MSCs from TNFα-induces apoptosis. The administration of surface engineered MSCs to hearts results in significant improvements in engraftment, cardiac function, infarct size, and vascularity compared with using uncoated MSCs in treating myocardial infarction. The surface-anchored, biocompatible cell surface engineering with nanogel armor provides a new way to produce robust therapeutic stem cells and may explore immense potentials in cell-based therapy.

Tumor circulome in the liquid biopsies for cancer diagnosis and prognosis.

Liquid biopsy is a convenient, fast, non-invasive and reproducible sampling method that can dynamically reflect the changes in tumor gene expression profile, and provide a robust basis for individualized therapy and early diagnosis of cancer. Circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) are the currently approved diagnostic biomarkers for screening cancer patients. In addition, tumor-derived extracellular vesicles (tdEVs), circulating tumor-derived proteins, circulating tumor RNA (ctRNA) and tumor-bearing platelets (TEPs) are other components of liquid biopsies with diagnostic potential. In this review, we have discussed the clinical applications of these biomarkers, and the factors that limit their implementation in routine clinical practice. In addition, the most recent developments in the isolation and analysis of circulating tumor biomarkers have been summarized, and the potential of non-blood liquid biopsies in tumor diagnostics has also been discussed.