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Objective: This study aimed to observe the effects of germinated brown rice and germinated black rice on blood lipid levels, blood glucose levels and lipid metabolism-related enzymes in T2DM patients with dyslipidaemia and to study their effects on the gut microbiome and short-chain fatty acids. Methods: According to the inclusion and exclusion criteria, 68 subjects were randomly divided into a germinated brown rice group, a germinated black rice group and a white rice group. At the end of the intervention, relevant anthropometric indices, blood biochemistry, and levels of adipokines and lipid metabolism-related enzymes were measured. Faecal samples were collected for 16S rDNA high-throughput sequencing and for an analysis of short-chain fatty acids. Results: After 3 months of intervention with germinated brown rice, germinated black rice or white rice, 21 people in each group completed the intervention as required. At the end of the intervention, the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the germinated brown rice group and germinated black rice group were significantly lower than those in the white rice group. The levels of adiponectin (ADPN) and lecithin cholesterol acyltransferase (LCAT) in the germinated brown rice group were significantly higher than those in the white rice group (P < 0.05). At the genus level, interventions with germinated brown rice and germinated black rice significantly increased the relative abundance of Megamonas, Muribaculaceae and Alloprevotella and significantly decreased the relative abundance of Veillonella (P < 0.05). After 3 months of intervention, a significant decrease in waist circumference was observed within the germinated brown rice group compared to that at baseline (P < 0.05). Conclusions: Compared with the consumption of white rice, the consumption of germinated brown rice and germinated black rice can effectively regulate the glucose and lipid metabolism of this population. In addition, interventions involving the use of germinated brown rice and germinated black rice may further improve intestinal diversity and abundance, increase the relative abundance of Megamonas and decrease the relative abundance of Veillonella.
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PURPOSE: In gestational diabetes (GDM), abnormalities occur not only in glucose metabolism, but also in lipid metabolism. Adiponectin (ADPN) plays an important role in the regulation of lipid metabolism. In this paper, the role and mechanism of ADPN in GDM are discussed. METHODS: GDM model was formed in pregnant mice induced by high-fat diet and streptozotocin, and blood glucose level was detected after ADPN treatment. The levels of TG, TC, HDL-C, and LDL-C in blood lipid of mice were detected by biochemical apparatus. HE staining was used to detect the placenta damage in mice. The expression of oxidative stress-related indexes in placental tissues was also detected by ELISA. Placental iron deposition was detected by Prussian blue staining. Redox capacity of placental tissue was detected by ELISA. Western blot was used to detect the expression of ferroptosis-related proteins in placental tissues. The expression of ADPN in placenta and peripheral blood was detected by ELISA, and the expression of ADPNR, downstream CPT-1, and GLUT4 of placenta were detected by RT-qPCR and western blot. Subsequently, trophoblast cells were induced by palmitic acid and glucose, and the cell activity was detected by CCK-8. The results in animal experiments were verified in cell experiments by RT-qPCR, western blot, and fluorescence labeling of iron ions. Finally, ADPN and CPT-1 inhibitor PM were given to trophoblast cells to further explore the mechanism. RESULTS: ADPN inhibited blood glucose and lipid levels in GDM mice. ADPN inhibited oxidation/peroxide imbalance-induced ferroptosis in placental tissues of GDM mice. ADPN inhibited the expression of CPT-1 and GLUT4 in placental tissues of GDM mice. This result was also confirmed in cell experiments, and this process may be achieved by regulating CPT-1. CONCLUSIONS: ADPN ameliorated placental injury in GDM by correcting fatty acid oxidation/peroxide imbalance-induced ferroptosis via restoration of CPT-1 activity.
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Adiponectina , Carnitina O-Palmitoiltransferase/metabolismo , Diabetes Gestacional , Ferroptose , Metabolismo dos Lipídeos , Placenta , Adiponectina/metabolismo , Animais , Ácidos Graxos/metabolismo , Feminino , Transportador de Glucose Tipo 4 , Camundongos , Estresse Oxidativo , Peróxidos/metabolismo , Placenta/metabolismo , Placenta/fisiopatologia , GravidezRESUMO
Diabetes mellitus (DM) is a type of metabolic disorder characterized by long-term hyperglycemia. Accumulating evidence shows that long noncoding RNAs (lncRNAs) play significant roles in the occurrence and development of DM. This study intended to investigate the role of lncRNA plasmacytoma variant translocation 1 (PVT1) in rat insulinoma (INS-1) cells damaged by streptozotocin (STZ) and to identify the potential mechanisms. Firstly, PVT1 expression in INS-1 cells was assessed using RT-qPCR after STZ stimulation. After PVT1-knockdown, cell apoptosis, the contents of oxidative stress related markers, and changes in insulin secretion were detected. Results indicated that PVT1 was remarkably upregulated after STZ stimulation. PVT1-knockdown inhibited STZ-induced oxidative stress and apoptosis of INS-1 cells. Moreover, the insulin secretory capacity was notably elevated following PVT1 silencing. Subsequently, a luciferase reporter assay verified that miR-181a-5p was directly targeted by PVT1. The rescue assays revealed that miR-181a-5p inhibitor dramatically abrogated the effects of PVT1 silencing on oxidative stress, apoptosis, and insulin secretion. Taken together, these findings demonstrated that PVT1-knockdown could ameliorate STZ-induced oxidative stress and apoptosis and elevate insulin secretory capacity in pancreatic ß cells by regulating miR-181a-5p, suggesting a promising biomarker in DM diagnosis and treatment.
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Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/terapia , Terapia Genética , Secreção de Insulina/genética , Células Secretoras de Insulina/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Inativação Gênica , Insulinoma/genética , MicroRNAs/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Neoplasias Pancreáticas/genética , RatosRESUMO
Diabetic osteoporosis (DOP) is attributed to the aberrant physiological function of bone marrow mesenchymal stem cells (BMSCs) under high glucose (HG) environment. MicroRNAs (miRNAs) are involved in the pathological processes of DOP. We aimed to explore the underlying mechanism of miRNA in DOP. BMSCs were cultured in osteogenic medium with HG to induce osteogenic differentiation, and the interaction between miR-493-5p and ZEB2 was assessed by luciferase assay. Herein, we found miR-493-5p is gradually reduced during osteogenic differentiation in BMSCs. HG treatment inhibits osteogenic differentiation and induces an up-regulation of miR-493-5p leading to reduced level of its downstream target ZEB2. Inhibition of miR-493-5p attenuates HG-induced osteogenic differentiation defects by upregulation of ZEB2. Mechanistically, miR-493-5p/ZEB2 signalling mediates HG-inhibited osteogenic differentiation by inactivation of Wnt/ß-catenin signalling. More importantly, knockdown of miR-493-5p therapeutically alleviated the DOP condition in mice. HG prevents BMSCs osteogenic differentiation via up-regulation of miR-493-5p, which results in reduced level of ZEB2 by directly targeting its 3'-untranslated region of mRNA. Thus, miR-493-5p/ZEB2 is a potential therapeutic target and provides novel strategy for the treatment and management of DOP.
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Complicações do Diabetes/metabolismo , Glucose/farmacologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Osteogênese/efeitos dos fármacos , Osteoporose/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Osteogênese/genética , Osteoporose/genética , Transfecção , Regulação para Cima/genética , Via de Sinalização Wnt/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , beta Catenina/metabolismoRESUMO
Neuregulin 4 (Nrg4) play important roles in the pathogenesis of obesity-associated disorders, including type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). This study aims to investigate roles of Nrg4 in the pathophysiologic mechanism underlying the progression of tubulointerstitial fibrosis (TIF) in diabetic nephropathy (DN). In present study, Nrg4 is under-expression in serum and renal tissue of diabetic nephropathy rats. In present study, Nrg4 attenuate renal function injury, tubulointerstitial fibrosis, inflammation and suppress the expression levels of advanced glycosylation end products (AGEs) in vivo and vitro. Furthermore, the results reveal that Nrg4 ameliorates fibrosis and attenuate the expression of AGEs and inflammation via TNF-R1 signaling instead of TNF-R2 signaling in HK-2 cells. In conclusion, these results revealed that Nrg4 may effectively ameliorates TIF and attenuate the expression of AGEs in DN through TNF-R1 signaling instead of TNF-R2 signaling. We have provided evidence indicating that Nrg4 possesses therapeutic effect on TIF in DN.
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OBJECTIVES: Lipopolysaccharide (LPS) contributed to the development and progression of type 2 diabetes mellitus (T2D), while TLR4 is reported to mediate the LPS-induced inflammation in macrophages. However, the potential molecular mechanisms for TLR4-mediated macrophages activation in T2D have not yet to be fully clarified. METHODS: Type 2 diabetes models in C57BL/6J mice were generated by a combination administration of streptozotocin (STZ) and a high-fat diet (HFD). Cell proportions of M1 and M2 macrophages were analyzed using flow cytometry. Expression profiles of miR-448 and TLR 4 were determined by qRT-PCR and Western blot. KEY FINDINGS: LPS/IFN-γ significantly induced M1 polarization in macrophages characterized by the increased levels of TNF-α, IL-6, IL-12, iNOS and decreased levels of TNF-ß, CCL-22, IL-10 and Arg-1, with a higher expression of toll-like receptor 4 (TLR4) in vitro. Consistently, T2D mice-derived macrophages had a significantly elevated expression of TLR4 mRNA and decreased expression of miR-448. We further confirmed that miR-448 could inhibit TLR4 expression by targeting the 3'-UTR of TLR4, rescuing the LPS/IFN-γ-induced M1 macrophage polarization. CONCLUSIONS: Taken together, our results indicated that decreased miR-448 in diabetic macrophages may contribute to LPS-induced M1 polarization by targeting TLR4, thereby modulating T2D development.
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Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Macrófagos Peritoneais/metabolismo , MicroRNAs/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Arginase/metabolismo , Técnicas de Cultura de Células , Polaridade Celular/efeitos dos fármacos , Polaridade Celular/fisiologia , Quimiocina CCL22/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Interferon-alfa/metabolismo , Interleucina-18/metabolismo , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos , Macrófagos Peritoneais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , RNA/genética , RNA/metabolismo , Receptor 4 Toll-Like/genética , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
[Ir(COD)Cl]2/tris(2,4-di-t-butylphenyl)phosphite-catalyzed addition reactions of arylboronic acids with aldehydes were described. The Ir(I) catalyst, generated from [Ir(COD)Cl]2 and tris(2,4-di-t-butylphenyl)phosphite, was an efficient catalyst system for the addition reactions of a variety of arylboronic acids with aromatic and aliphatic aldehydes. The easy availability of the catalyst and good yields make these reactions potentially useful in organic synthesis.
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Controlled Pd(0)-catalyzed Suzuki cross-coupling polymerizations of AB-type monomers with tris(1-adamantyl)phosphine (Ad3P) as the ligand was described. Ad3P-coordinated acetanilide-based palladacycle complex (1) was demonstrated to be an efficient initiator for controlled Suzuki cross-coupling polymerization, affording polymers with narrow Ds and well-controlled end groups. Our study provided an efficient ligand and an efficient initiator for controlled Suzuki cross-coupling polymerizations.
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t-Bu3P-coordinated 2-phenylaniline-based palladacycle complex (1) as the unique source of Pd(0)/t-Bu3P to form efficient initiators with ArBr for controlled Suzuki cross-coupling polymerizations of AB-type monomers was described. The in situ generated initiators were demonstrated to be robust initiator systems for controlled Suzuki cross-coupling polymerization, affording polymers with unprecedentedly narrow PDIs and well-controlled functional end groups. 31P NMR study suggested that the fast and efficient generation of ArPd(t-Bu3P)Br complexes from precatalyst 1 and ArBr might be the reason for better control of polymerization with precatalyst 1/ArBr as initiators. Our study provided a family of unprecedented, highly efficient initiators for controlled Suzuki cross-coupling polymerizations and a direct route to access conjugated polymers with a variety of heterobisfunctional chain end groups.
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The use of electron-poor, fluoro-containing arylboronic acids as general coupling partners for nickel(0) /tricyclohexylphosphine-catalyzed cross-coupling of aryl arenesulfonates is described. Electron-poor fluoro-containing arylboronic acids were found to react, faster than electron-rich/neutral arylboronic acids, with (4-methoxyphenyl)(4-methylbenzenesulfonato-κO)bis(tricyclohexylphosphine)nickel. Bis(1,5-cyclooctadiene)nickel(0)/tricyclohexylphosphine, (4-methoxyphenyl)(4-methylbenzenesulfonato-κO)bis(tricyclohexylpho sphine)nickel and bis(tricyclohexylphosphine)nickel (II) bromide were all found to be efficient catalysts/catalyst precursors.
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A general strategy toward the synthesis of well-defined conjugated polymers with controlled heterobisfunctional chain ends via combination of controlled Pd(0)/t-Bu3P Suzuki cross-coupling polymerization with the post-polymerization modification of the triflate (OTf) group was disclosed.
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tBu3P-Coordinated 2-phenylaniline-based palladacycle complex was demonstrated to be an efficient precatalyst for Pd-catalyzed coupling reactions of aryl halides with polyfluoroarenes via C-H activation strategy. The readily accessibility and easy handling nature of tBu3P- coordinated 2-aminobiphenyl-based palladacycle complex and the high yields of the reaction makes tBu3P-coordinated 2-aminobiphenyl-based palladacycle complex an attractive precatalyst for the cross-coupling reaction of aryl halides with polyfluoroarenes.
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t -Bu3P-Coordinated 2-phenylaniline-based palladacycle complex, [2'-(amino-kN)[1,1'-biphenyl]-2-yl-kC]chloro(tri-t-butylphosphine)palladium, as a general, highly efficient precatalyst for the Suzuki cross-coupling polymerization of aryl dibromides with aryldiboronic acids is described. Such t-Bu3P-coordinated 2-aminobiphenyl-based palladacycle complex-catalyzed Suzuki cross-coupling polymerization afforded polymers within an hour, with the yields and the molecular weights comparable to or higher than that of polymers obtained by using other palladium catalysts with much longer polymerization time. Our study provided a highly efficient catalyst system for the Suzuki cross-coupling polymerization of aryl dihalides with aryldiboronic acids. Our study also paved the road for us to investigate other monodentate ligand-coordinated palladacycle complexes including N-heterocyclic carbine-coordinated ones for cross-coupling polymerizations.
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The title compound, C(18)H(14)O(2), is almost planar with a dihedral angle of 1.24â (2)° between the phenyl-ethynyl and styryl groups. The acet-oxy group is tilted by 82.46â (2) and 82.26â (3)° with respect to the benzene ring planes.
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Controlled Pd(0)/t-Bu(3)P-catalyzed Suzuki cross-coupling polymerizations of AB-type monomers via the chain-growth mechanism with an ArPd(t-Bu(3)P)I complex as the initiator are described. ArPd(t-Bu(3)P)I complexes, either prepurified or generated in situ from Pd(2)(dba)(3)/t-Bu(3)P/ArI (dba = dibenzylideneacetone) without separation/purification, were found to be efficient initiators in general for the controlled Suzuki cross-coupling polymerization, with narrow polydispersity indexes (PDIs) of 1.13-1.35 being observed. The Pd(2)(dba)(3)/t-Bu(3)P/p-BrC(6)H(4)I combination was identified as a highly robust initiator system, with PDIs of ≤1.20 in general and as low as 1.13 being obtained. Higher number-average molecular weights (M(n)) were achieved without a significant increase in the PDI (from 1.14 for a polymer with a M(n) = 9500 to 1.20 for a polymer with M(n) = 31,400) by using a smaller amount of the Pd(2)(dba)(3)/t-Bu(3)P/p-BrC(6)H(4)I initiator in the polymerization.
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Rh(I)/diene-catalyzed addition reactions of arylboroxines/arylboronic acids with unactivated ketones to form tertiary alcohols in good to excellent yields are described. By using C(2)-symmetric (3aR,6aR)-3,6-diaryl-1,3a,4,6a-tetrahydropentalenes as ligands, the asymmetric version of such an addition reaction, with up to 68% ee, was also realized.
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Álcoois/síntese química , Ácidos Borônicos/química , Cetonas/química , Ródio/química , Álcoois/química , Catálise , Técnicas de Química Combinatória , Estrutura MolecularRESUMO
Tandem aldol condensation of aldehydes with methyl ketones followed by anionic four-electron donor-based (Type I) platinacycle-catalyzed addition reactions of arylboronic acids to form ß-arylated ketones is described. Good to excellent yields of ß-arylated ketones were obtained for the tandem reactions of aromatic/aliphatic aldehydes, methyl ketones and arylboronic acids, and moderate yields were observed for the tandem reaction with α, ß-unsaturated aldehydes as the aldehyde source.
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CuCl/bipyridine-catalyzed addition reactions of arylboroxines with aldehydes and α,ß-unsaturated ketones at elevated temperatures were described. By using the microwave energy, CuCl/bipyridine-catalyzed addition reactions of arylboroxines with aldimines were also realized.
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RuCl3·3H2O was found to be an effective catalyst for reactions of indoles, 2-methylthiophene, and 2-methylfuran with aldehydes to afford the corresponding bis(indolyl)methanes, bis(thienyl)methanes, and bis(fur-2-yl)methanes in moderate to excellent yields. Experimental results indicated that mono(indolyl)methanol is not the reaction intermediate under these reaction conditions.
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Metano/análogos & derivados , Metano/síntese química , Rutênio/química , Catálise , Metano/química , Estrutura MolecularRESUMO
A new, anionic four-electron donor-based (type I) palladacycle-catalyzed sequential reaction of 2-bromobenzaldehydes with arylboronic acids based on the addition reaction, cyclization via C-H activation-oxidation sequence is described. Our study provided an efficient access to a variety of substituted fluorenones/indenofluorenediones from readily available arylboronic acids and 2-bromobenzaldehydes.