Differentiation of gestational diabetes mellitus by nuclear magnetic resonance-based metabolic plasma analysis

This study aimed to investigate the metabolic profile of gestational diabetes mellitus(GDM)at both antepartum and postpartum periods.Seventy pregnant women were divided into three groups:the normal glucose-tolerant group(NGT,n=35),the abnormal glucose-tolerant groups without insulin therapy(A1GDM,n=24)or with insulin therapy(A2GDM,n=11).Metabolic profiles of the plasma were acquired by proton nuclear magnetic resonance(1H-NMR)spectroscopy and analyzed by multivariate statistical data analysis.The relationship between demographic parameters and the potential metabolite biomarkers was further explored.Group antepartum or postpartum showed similar metabolic trends.Compare with those of the NGT group,the levels of 2-hydroxybutyrate,lysine,acetate,glutamine,succinate,tyrosine,formate,and all three BCAAs(leucine,valine,isoleucine)in the A2GDM group were increased dramatically,and the levels of lysine,acetate,and formate in the A1GDM group were elevated significantly.The dramatically decreased levels of 3-methyl-2-oxovalerate and methanol were observed both in the A1GDM group and A2GDM group.Compare to the A1GDM group,the branched-chain amino acids(BCAAs)of leucine,valine,and isoleucine were increased dramatically in the A2GDM group.The levels of aromatic amino acids(AAAs),tyrosine and phenylalanine,were significantly increased in GDM women,consistent with the severity of GDM.Interference of amino acid metabolism and disturbance in energy metabolism occurred in women with different grades of GDM.Metabolic profiles could reflect the severity of GDM.Plasma BCAA concentrations showing strong positive correlations with weight and pre-delivery BMI.This study provides a new perspective to understand the pathogenesis and etiology of GDM,which may help the clinical management and treatment of GDM.

Piceatannol attenuates streptozotocin-induced type 1 diabetes inmice

As a natural analog of resveratrol,piceatannol(Pic)exhibits good antioxidant and anti-inflammatory activities in different disease models.However,the role of Pic in type 1 diabetes mousemodel has not been reported yet.In this study,we investigated the in vivo effect of Pic in streptozotocin(STZ)-induced type 1 diabetic mice.Mice were injected with STZ to establish the type 1 diabetesmellitus(T1DM)model.After stable hyperglycemia was achieved,mice were then orally treated with Pic(40 mg/kg b.w.,i.g.)for 30 days.The results indicated that Pic supplementation efficiently alleviated the typical symptoms associated with T1DM,including body weight loss,polydipsia,hyperglycemia,and hypoinsulinemia.Pic treatment also improved the glucose tolerance of STZ-induced diabetic mice.In addition,Pic supplementation markedly decreased the expression of pro-inflammatory molecules TNF-αand IL-6,the expression of endoplasmic reticulum(ER)stress markers GRP78 and CHOP,and the level of oxidative stress in T1DM mice.Moreover,Pic administration also partly reversed the metabolic profiles of STZ-treated mice as detected by 1H Nuclear Magnetic Resonance(NMR)-based metabolomics.Our study suggested that the therapeutic potential of Pic in type 1 diabetes and the anti-diabetic effects of Pic may be associated with its activities to suppress oxidative stress,inflammation,and ER stress.

Hot deformation characteristics and hot working window of as-cast large-tonnage GH3535 superalloy ingot

Deformation characteristics and range of optimized hot working parameters of a 6.5 tons GH3535 superalloy ingot with an average columnar grain size of over 1 mm in diameter were investigated. Axial compression experiments were performed in temperature range of 900-1240 ℃ and strain rate range of 0.001-30 s;at a total strain of 0.8. The hot deformation activation energy of the experimental GH3535 alloy is calculated to be 483.22 kJ/mol. Furthermore, the deformation constitutive equation is established by the peak stresses obtained from the stress-strain curves under various conditions. The hot working window of the alloy ingot at a strain of 0.8 can be preliminarily discussed based on the deformed microstructures and processing maps. The optimized hot working window was thus determined at the strain of 0.95 for 6.5 tons GH3535 alloy ingot by the supplementary compression tests. A large-size GH3535 superalloy ring with a dimension of 03010 mm x 410 mm was ultimately manufactured.

Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-β1/Smad axis

Background:Amphibian-derived peptides exhibit considerable potential in the discovery and development of new therapeutic interventions for clinically challenging chronic skin wounds.MicroRNAs(miRNAs)are also considered promising targets for the development of effective therapies against skin wounds.However,further research in this field is anticipated.This study aims to identify and provide a new peptide drug candidate,as well as to explore the underlying miRNA mechanisms and possible miRNA drug target for skin wound healing.Methods:A combination of Edman degradation,mass spectrometry and cDNA cloning were adopted to determine the amino acid sequence of a peptide thatwas fractionated from the secretion of Odorrana andersonii frog skin using gel-filtration and reversed-phase high-performance liquid chromatography.The toxicity of the peptide was evaluated by Calcein-AM/propidium iodide(PI)double staining against human keratinocytes(HaCaT cells),hemolytic activity against mice blood cells and acute toxicity against mice.The stability of the peptide in plasma was also evaluated.The prohealing potency of the peptide was determined by MTS,scratch healing and a Transwell experiment against HaCaT cells,full-thickness injury wounds and scald wounds in the dorsal skin of mice.miRNA transcriptome sequencing analysis,enzyme-linked immunosorbent assay,real-time polymerase chain reaction and western blotting were performed to explore the molecular mechanisms.Results:A novel peptide homodimer(named OA-GL17d)that contains a disulfide bond between the 16th cysteine residue of the peptide monomer and the sequence‘GLFKWHPRCGEEQSMWT’was identified.Analysis showed that OA-GL17d exhibited no hemolytic activity or acute toxicity,but effectively promoted keratinocyte proliferation and migration and strongly stimulated the repair of full-thickness injury wounds and scald wounds in the dorsal skin of mice.Mechanistically,OA-GL17d decreased the level of miR-663a to increase the level of transforming growth factor-β1(TGF-β1)and activate the subsequent TGF-β1/Smad signaling pathway,thereby resulting in accelerated skin wound re-epithelialization and granular tissue formation.Conclusions:Our results suggest that OA-GL17d is a new peptide drug candidate for skin wound repair.This study emphasizes the importance of exogenous peptides as molecular probes for exploring competing endogenous RNA mechanisms and indicates that miR-663a may be an effective target for promoting skin repair.