Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption,...Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption, intracellular glycogen content, phosphorylation of PI3K and Akt stimulated by insulin, expression of miR-455-5p, as well as IGF-1R protein level were analyzed. In addition, bioinformatic analysis, dual luciferase reporter assay, miR- 455-5p mimic or inhibitor treatment was conducted to investigate the molecular mechanisms. Results: High glucose treatment upregulated miR-455-5p expression but reduced glucose consumption and glycogen content. DAG reversed the effect of high glucose on glucose metabolism, increased protein level of IGF-1R and phosphorylation of PI3K/Akt stimulated by insulin, as well as downregulated miR-455-5p expression. Bioinformatic analysis indicated IGF-1R was the target of miR-455-5p. Dual luciferase reporter assay, as well as transfection with miR-455-5p mimic/inhibitor confirmed that DAG activated IGF-1R/PI3K/Akt signaling via inhibiting miR-455-5p. Conclusion: DAG improves insulin resistance via miR-455-5p- mediated activation of IGF-1R/PI3K/Akt system, suggesting that suppression of miR-455-5p or activation of DAG may be potential targets for T2DM therapy.展开更多
Caenorhabditis elegans （C. elegans） was used as an animal model to study the effect of （-）-5-hydroxy-equol, a microbialmetabolite of isoflavone genistein, on the lifespan, fecundity and resistance against thermal ...Caenorhabditis elegans （C. elegans） was used as an animal model to study the effect of （-）-5-hydroxy-equol, a microbialmetabolite of isoflavone genistein, on the lifespan, fecundity and resistance against thermal and oxidative stress. The resultsshowed that （-）-5-hydroxy-equol not only significantly increased the lifespan of C. elegans but also significantly enhancedthe resistance against thermal and oxidative stress at the concentrations of 0.1 mmol/L and 0.2 mmol/L. However, the fecundityof C. elegans was not obviously influenced after being exposed to the same concentrations of （-）-5-hydroxy-equol. Further studieson comparative transcriptome analyses and the lifespan ofdaf-16 （mu86） mutant and daf-2 （e1370） mutant indicated that（-）-5-hydroxy-equol prolonged the lifespan of C. elegans through DAF-2/DAF-16 Insulin/IGF-1 signaling pathway. This isthe first report that （-）-5-hydroxy-equol was able to increase the lifespan and improve the thermal and oxidative stress toleranceof C. elegans.展开更多
A new conjugated copolymer （PTST-DyOXD） derived from 1,1-dimethyl-3,4-diphenyl-2,5-bis（5-bromo-2- thienyl）-silole （TST） and 2,5-bis（4-ethynylphenyl）-l,3,4-oxadiazole （DyOXD） was synthesized by Pd（0）-cataly...A new conjugated copolymer （PTST-DyOXD） derived from 1,1-dimethyl-3,4-diphenyl-2,5-bis（5-bromo-2- thienyl）-silole （TST） and 2,5-bis（4-ethynylphenyl）-l,3,4-oxadiazole （DyOXD） was synthesized by Pd（0）-catalyzed Sonogashira coupling reaction. For comparison, another copolymer without acetenyl group （PTST-OXD） was also synthesized by Pd（0）-catalyzed Suzuki coupling reaction. Chemical structures and optoelectronic properties of the copolymers were characterized by IH NMR, 13C NMR, IR, UV-vis absorption, photoluminescence and cyclic voltammetry. The number-average molecular weight （Mn） is 4010 Da for PTST-DyOXD and 3890 Da for PTST-OXD, respectively. The thermogravimetric analysis （TGA） measurements show that they have good thermal stability with decomposition temperature at 312 and 318 ~C, respectively. The optical band gap is 2.21 eV for PTST-DyOXD and 2.10 eV for PTST-OXD based on the absorption onset. CV analysis revealed the LUMO level of PTST-DyOXD is -3.04 eV, lower than that of PTST-OXD （about -2.89 eV）, which is attributed to the introduction of acetylene group in PTST-DyOXD, increasing the system of the conjugate chain length.展开更多
基金Changshu Science and Technology Plan(Social Development)Project(No.CS202130)Key Project of Changshu No.2 People’s Hospital(No.CSEY2021007)。
文摘Objective: To explore the mechanism by which ghrelin regulates insulin sensitivity through modulation of miR-455-5p in hepatic cells. Methods: HepG2 cells were treated with or without DAG (1 μM). Glucose consumption, intracellular glycogen content, phosphorylation of PI3K and Akt stimulated by insulin, expression of miR-455-5p, as well as IGF-1R protein level were analyzed. In addition, bioinformatic analysis, dual luciferase reporter assay, miR- 455-5p mimic or inhibitor treatment was conducted to investigate the molecular mechanisms. Results: High glucose treatment upregulated miR-455-5p expression but reduced glucose consumption and glycogen content. DAG reversed the effect of high glucose on glucose metabolism, increased protein level of IGF-1R and phosphorylation of PI3K/Akt stimulated by insulin, as well as downregulated miR-455-5p expression. Bioinformatic analysis indicated IGF-1R was the target of miR-455-5p. Dual luciferase reporter assay, as well as transfection with miR-455-5p mimic/inhibitor confirmed that DAG activated IGF-1R/PI3K/Akt signaling via inhibiting miR-455-5p. Conclusion: DAG improves insulin resistance via miR-455-5p- mediated activation of IGF-1R/PI3K/Akt system, suggesting that suppression of miR-455-5p or activation of DAG may be potential targets for T2DM therapy.
基金National Natural Science Foundation of China(Grant No.31170058)the Service Center for Experts and Scholars of Hebei Province(Grant No.CPRC027)
文摘Caenorhabditis elegans （C. elegans） was used as an animal model to study the effect of （-）-5-hydroxy-equol, a microbialmetabolite of isoflavone genistein, on the lifespan, fecundity and resistance against thermal and oxidative stress. The resultsshowed that （-）-5-hydroxy-equol not only significantly increased the lifespan of C. elegans but also significantly enhancedthe resistance against thermal and oxidative stress at the concentrations of 0.1 mmol/L and 0.2 mmol/L. However, the fecundityof C. elegans was not obviously influenced after being exposed to the same concentrations of （-）-5-hydroxy-equol. Further studieson comparative transcriptome analyses and the lifespan ofdaf-16 （mu86） mutant and daf-2 （e1370） mutant indicated that（-）-5-hydroxy-equol prolonged the lifespan of C. elegans through DAF-2/DAF-16 Insulin/IGF-1 signaling pathway. This isthe first report that （-）-5-hydroxy-equol was able to increase the lifespan and improve the thermal and oxidative stress toleranceof C. elegans.
基金The authors are grateful to financial support from the National Natural Science Foundation of China，the East China University of Science and Technology
文摘A new conjugated copolymer （PTST-DyOXD） derived from 1,1-dimethyl-3,4-diphenyl-2,5-bis（5-bromo-2- thienyl）-silole （TST） and 2,5-bis（4-ethynylphenyl）-l,3,4-oxadiazole （DyOXD） was synthesized by Pd（0）-catalyzed Sonogashira coupling reaction. For comparison, another copolymer without acetenyl group （PTST-OXD） was also synthesized by Pd（0）-catalyzed Suzuki coupling reaction. Chemical structures and optoelectronic properties of the copolymers were characterized by IH NMR, 13C NMR, IR, UV-vis absorption, photoluminescence and cyclic voltammetry. The number-average molecular weight （Mn） is 4010 Da for PTST-DyOXD and 3890 Da for PTST-OXD, respectively. The thermogravimetric analysis （TGA） measurements show that they have good thermal stability with decomposition temperature at 312 and 318 ~C, respectively. The optical band gap is 2.21 eV for PTST-DyOXD and 2.10 eV for PTST-OXD based on the absorption onset. CV analysis revealed the LUMO level of PTST-DyOXD is -3.04 eV, lower than that of PTST-OXD （about -2.89 eV）, which is attributed to the introduction of acetylene group in PTST-DyOXD, increasing the system of the conjugate chain length.
