PPM1A Controls Diabetic Gene Programming through Directly Dephosphorylating PPAR?? at Ser273

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master regulator of adipose tissue biology. In obesity, phosphorylation of PPAR gamma at Ser273 (pSer273) by cyclin-dependent kinase 5 (CDK5)/extracellular signal-regulated kinase (ERK) orchestrates diabetic gene reprogramming via dysregulation of specific gene expression. Although many recent studies have focused on the development of non-classical agonist drugs that inhibit the phosphorylation of PPAR gamma at Ser273, the molecular mechanism of PPAR gamma dephosphorylation at Ser273 is not well characterized. Here, we report that protein phosphatase Mg2+/Mn2+-dependent 1A (PPM1A) is a novel PPAR gamma phosphatase that directly dephosphorylates Ser273 and restores diabetic gene expression which is dysregulated by pSer273. The expression of PPM1A significantly decreases in two models of insulin resistance: diet-induced obese (DIO) mice and db/db mice, in which it negatively correlates with pSer273. Transcriptomic analysis using microarray and genotype-tissue expression (GTEx) data in humans shows positive correlations between PPM1A and most of the genes that are dysregulated by pSer273. These findings suggest that PPM1A dephosphorylates PPAR gamma at Ser273 and represents a potential target for the treatment of obesity-linked metabolic disorders

Cooperative evolution of polar distortion and nonpolar rotation of oxygen octahedra in oxide heterostructures

Polarity discontinuity across LaAlO3/SrTiO3 (LAO/STO) heterostructures induces electronic reconstruction involving the formation of two-dimensional electron gas (2DEG) and structural distortions characterized by antiferrodistortive (AFD) rotation and ferroelectric (FE) distortion. We show that AFD and FE modes are cooperatively coupled in LAO/STO (111) heterostructures; they coexist below the critical thickness (t(c)) and disappear simultaneously above tc with the formation of 2DEG. Electron energy-loss spectroscopy and density functional theory (DFT) calculations provide direct evidence of oxygen vacancy (VO) formation at the LAO (111) surface, which acts as the source of 2DEG. Tracing the AFD rotation and FE distortion of LAO reveals that their evolution is strongly correlated with VO distribution. The present study demonstrates that AFD and FE modes in oxide heterostructures emerge as a consequence of interplay between misfit strain and polar field, and further that their combination can be tuned to competitive or cooperative coupling by changing the interface orientation

Collagen Immobilization on Ultra-thin Nanofiber Membrane to Promote In Vitro Endothelial Monolayer Formation

The endothelialization on the poly (epsilon-caprolactone) nanofiber has been limited due to its low hydrophilicity. The aim of this study was to immobilize collagen on an ultra-thin poly (epsilon-caprolactone) nanofiber membrane without altering the nanofiber structure and maintaining the endothelial cell homeostasis on it. We immobilized collagen on the poly (epsilon-caprolactone) nanofiber using hydrolysis by NaOH treatment and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo-N-hydroxysulfosuccinimide reaction as a cost-effective and stable approach. NaOH was first applied to render the poly (epsilon-caprolactone) nanofiber hydrophilic. Subsequently, collagen was immobilized on the surface of the poly (epsilon-caprolactone) nanofibers using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo-N-hydroxysulfosuccinimide. Scanning electron microscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, and fluorescence microscopy were used to verify stable collagen immobilization on the surface of the poly (epsilon-caprolactone) nanofibers and the maintenance of the original structure of poly (epsilon-caprolactone) nanofibers. Furthermore, human endothelial cells were cultured on the collagen-immobilized poly (epsilon-caprolactone) nanofiber membrane and expressed tight junction proteins with the increase in transendothelial electrical resistance, which demonstrated the maintenance of the endothelial cell homeostasis on the collagen-immobilized-poly (epsilon-caprolactone) nanofiber membrane. Thus, we expected that this process would be promising for maintaining cell homeostasis on the ultra-thin poly (epsilon-caprolactone) nanofiber scaffolds.11Ysciescopu

α-amylase and α-glucosidase inhibition effects of Korean edible brown, green, and red seaweed extracts

The control of intestinal α-amylase and α-glucosidase is an effective therapeutic strategy for prevention of post-prandial hyperglycemia associated with diabetes mellitus. The objective of this study was to evaluate the anti-diabetes activities of Korean edible seaweed against α-amylase and α-glucosidase, two carbolytic enzymes involved in serum glucose regulation. Of the 41 species initially screened, Cladophora wrightiana var. minor, Eisenia bicyclis, Ecklonia cava, Ishige foliacea, and Ishige okamurae exhibited the strongest inhibitory activities from brown seaweeds. Asparagopsis taxiformis showed the strongest inhibitory effects from red seaweeds. The results of this study suggest that the crude brown seaweed extracts (C. wrightiana var. minor, E. bicyclis, E. cava, I. foliacea, and I. okamurae) and crude red seaweed extracts (A. taxiformis) may have beneficial effects suppressing the rise in postprandial hyperglycemia through the inhibition of α-amylase and α-glucosidase

Cognitive-Enhancing Effect of Steamed and Fermented Codonopsis lanceolata

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory impairment. Codonopsis lanceolata (C. lanceolata) has been employed clinically for lung inflammatory diseases such as asthma, tonsillitis, and pharyngitis. The present study was undertaken to evaluate the effect of fermented C. lanceolata (300, 500, and 800 mg/kg) on learning and memory impairment induced by scopolamine by using the Morris water maze and passive avoidance tests. To elucidate possible mechanism of cognitive-enhancing activity, we measured acetylcholinesterase (AchE) activity, brain-derived neurotrophic factor (BDNF), and cyclic AMP response element-binding protein (CREB) expression in the brain of mice. Administration of fermented C. lanceolata (800 mg/kg) led to reduced scopolamine-induced memory impairment in the Morris water maze and passive avoidance tests. Accordingly, the administration of fermented C. lanceolata inhibited AchE activity. Interestingly, the level of CREB phosphorylation and BDNF expression in hippocampal tissue of scopolamine-treated mice was significantly increased by the administration of fermented C. lanceolata. These results indicate that fermented C. lanceolata can ameliorate scopolamine-induced memory deficits in mouse and may be an alternative agent for the treatment of AD