Antidiabetic activity of a polysaccharide-protein complex from Asian Clam (Corbicula fluminea) in streptozotoxin-induced diabetic rats and its underlying mechanism.

The antidiabetic activity and potential underlying mechanism of a polysaccharide-protein (PSP) complex from Corbicula fluminea were determined in streptozotoxin (STZ)-induced diabetic rats. PSP exhibited inhibitory activity (in vitro) against α-glucosidase and α-amylase via a reversible competitive inhibition pattern with a stronger inhibition for α-glucosidase. Dietary administration of PSP had potential antidiabetic activities in vivo, which was evidenced by the fact that PSP alleviates body weight loss and organ injuries, reduced fasting blood glucose levels, elevated glucose tolerance, and ameliorated lipid metabolism and hepatic functions, as well as attenuated oxidative stress in STZ-treated diabetic rats. Furthermore, our results demonstrated that the antidiabetic activities of PSP were associated with the activation of the phosphoinositide 3-kinase/protein kinase B signaling pathway in STZ-treated rats. These findings supported the potential of PSP to be used as a functional ingredient in the preparation of functional and medicinal foods to inhibit diabetes mellitus and its complications.

Maintenance of Nucleolar Homeostasis by CBX4 Alleviates Senescence and Osteoarthritis.

CBX4, a component of polycomb repressive complex 1 (PRC1), plays important roles in the maintenance of cell identity and organ development through gene silencing. However, whether CBX4 regulates human stem cell homeostasis remains unclear. Here, we demonstrate that CBX4 counteracts human mesenchymal stem cell (hMSC) aging via the maintenance of nucleolar homeostasis. CBX4 protein is downregulated in aged hMSCs, whereas CBX4 knockout in hMSCs results in destabilized nucleolar heterochromatin, enhanced ribosome biogenesis, increased protein translation, and accelerated cellular senescence. CBX4 maintains nucleolar homeostasis by recruiting nucleolar protein fibrillarin (FBL) and heterochromatin protein KRAB-associated protein 1 (KAP1) at nucleolar rDNA, limiting the excessive expression of rRNAs. Overexpression of CBX4 alleviates physiological hMSC aging and attenuates the development of osteoarthritis in mice. Altogether, our findings reveal a critical role of CBX4 in counteracting cellular senescence by maintaining nucleolar homeostasis, providing a potential therapeutic target for aging-associated disorders.

Three-phase partitioning for the direct extraction and separation of bioactive exopolysaccharides from the cultured broth of Phellinus baumii.

In this study, three-phase partitioning (TPP) was used to directly extract and separate bioactive exopolysaccharides (EPSs) from a cultured broth of Phellinus baumii. The maximum extraction yield of EPS was 52.09% under the following optimal conditions: 20% (w/v) ammonium sulfate concentration, 1.0:1.5 (v/v) ratio of cultured broth to t­butanol, 30 min, and 35 °C. A multifrequency power ultrasound in a sequential mode coupled with TPP resulted in ~9.12% increment in extraction yield and ~80% reduction in extraction time compared with those of traditional TPP. The carbohydrate (88.21%) and uronic acid (3.37%) contents of partially purified EPS were higher than those of EPS-C obtained through conventional ethanol precipitation and separation methods. EPS and EPS-C exhibited similar preliminary structural characteristics and different monosaccharide compositions and molecular weights. The radical-scavenging abilities, antioxidant capacities, α­amylase and α­glycosidase inhibitory activities, and macrophage stimulation activities of EPS were also higher than those of EPS-C. Therefore, it could be concluded that TPP as a simple and green separation technique could be used to directly extract and separate bioactive EPS from the fermentation broths of mushrooms and other fungi.

Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.

Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina-heterochromatin anchoring protein LAP2ß. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.

Progress and prospects in stem cell therapy.

In the past few years, progress being made in stem cell studies has incontestably led to the hope of developing cell replacement based therapy for diseases deficient in effective treatment by conventional ways. The induced pluripotent stem cells (iPSCs) are of great interest of cell therapy research because of their unrestricted self-renewal and differentiation potentials. Proof of principle studies have successfully demonstrated that iPSCs technology would substantially benefit clinical studies in various areas, including neurological disorders, hematologic diseases, cardiac diseases, liver diseases and etc. On top of this, latest advances of gene editing technologies have vigorously endorsed the possibility of obtaining disease-free autologous cells from patient specific iPSCs. Here in this review, we summarize current progress of stem cell therapy research with special enthusiasm in iPSCs studies. In addition, we compare current gene editing technologies and discuss their potential implications in clinic application in the future.