Chronic ethanol feeding impairs AMPK and MEF2 expression and is associated with GLUT4 decrease in rat myocardium

LiYong Chen,Jing Zhou,JiaJun Zhao,FuRong Wang,XiangLan Sun,Ling Gao,YuLian Jiao,XiaoLei Hou,ChengYong Qin 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.3

Chronic and heavy alcohol consumption is one of the causes of heart diseases. However, the effects of ethanol on insulin sensitivity in myocardium has been unclear. To investigate the effects of ethanol on the expression of AMP-activated protein kinase (AMPK), myocyte enhancer factor 2 (MEF2) and glucose transporter 4 (GLUT4), all of which are involved in the regulation of insulin sensitivity, in the myocardium, we performed three parts of experiments in vivo and in vitro. I: Rats were injected with 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR, 0.8 mg.kg-1) for 2 h. II:Rats received different dose (0.5, 2.5 or 5 g.kg-1.d-1) of ethanol for 22-week. III: Primary neonatal rat cardiomyocytes were isolated and treated with or without 100 mM ethanol or 1 mM AICAR for 4 h. The cardiac protein and mRNA expression of AMPKα subunits, MEF2and GLUT4 were observed by western-blotting and RT-PCR, respectively. Serum TNFα levels were assessed by ELISA. The results showed chronic ethanol exposure induced insulin resistance. Ethanol decreased the mRNA levels of AMPKα1 and α2, the protein levels of total- and phospho-AMPKα in cardiomyocytes. Similarly, ethanol showed inhibitory effects on both the mRNA and protein levels of MEF2A and 2D,and GLUT4 in a dose-response-like fashion. Correlation analysis implied an association between phospho-AMPKα and MEF2A or MEF2D, and between the levels of MEF2 protein and GLUT4 transcription. In addition,ethanol elevated serum TNFα level. Taken together,chronic ethanol exposure decreases the expression of AMPKα and MEF2, and is associated with GLUT4 decline in rat myocardium.

BET inhibitors synergize with sunitinib in melanoma through GDF15 suppression

Zeng Furong,Li Yayun,Meng Yu,Sun Huiyan,Yi He,Yin Mingzhu,Chen Xiang,Deng Guangtong 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Targeting bromodomain and extra-terminal domain (BET) proteins has shown a promising therapeutic effect on melanoma. The development of strategies to better kill melanoma cells with BET inhibitor treatment may provide new clinical applications. Here, we used a drug synergy screening approach to combine JQ1 with 240 antitumor drugs from the Food and Drug Administration (FDA)-approved drug library and found that sunitinib synergizes with BET inhibitors in melanoma cells. We further demonstrated that BET inhibitors synergize with sunitinib in melanoma by inducing apoptosis and cell cycle arrest. Mechanistically, BET inhibitors sensitize melanoma cells to sunitinib by inhibiting GDF15 expression. Strikingly, GDF15 is transcriptionally regulated directly by BRD4 or indirectly by the BRD4/IL6/STAT3 axis. Xenograft assays revealed that the combination of BET inhibitors with sunitinib causes melanoma suppression in vivo. Altogether, these findings suggest that BET inhibitor-mediated GDF15 inhibition plays a critical role in enhancing sunitinib sensitivity in melanoma, indicating that BET inhibitors synergize with sunitinib in melanoma.

Experimental investigation of influence of scratch features on GaAs cleavage plane during cleavage processing using a scratching capability index

Rui Gao,Chen Jiang,XiaoHu Lang,KangJia Dong,FuRong Li 한국정밀공학회 2021 International Journal of Precision Engineering and Vol.8 No.3

High-power semiconductor laser cavities are formed via the cleavage plane, and critically influence the reliability and performance of the laser. This paper investigates both the scratching operation and the cleavage operation to improve the quality of the cleavage plane during the entire cleavage process. The scratching capability index (SCI) variable was proposed to evaluate the scratch quality of GaAs. A series of scratching and cleavage experiments were carried out to investigate the effect of the scratch features on the GaAs cleavage plane. Experimental results of the scratching operation showed that a smaller scratching load and higher scratching speed were beneficial for reducing the kerf width and damage area width of GaAs. The cleavage operation on GaAs {100} cleavage planes exhibited crack propagation in the [1̄01̄] and [1̄00] directions and a slip direction in the <110> crystal direction. The calculated SCI variable correlated well with the scratch and cleavage qualities of GaAs, where a higher scratching SCI correlated with a smoother GaAs cleavage plane during cleavage processing. Thus, the SCI has the potential to relate the scratching parameters with the resulting cleavage plane quality of GaAs, which will help improve the manufacturing of semiconductor laser chips in the future.

Effect of Ultrasonic Power on the Microstructure and Properties of 304 Stainless Steel Welded Joints Through Cold Metal Transfer Welding Assisted with Ultrasonication

Fei Li,Furong Chen,Peihu Gao,Wei Wang,Chenlong Yang,Shiyuan Liu 대한금속·재료학회 2023 METALS AND MATERIALS International Vol.29 No.10

With the development of welding technology, low heat input and high efficiency cold metal transfer welding have become the main methods of thin plate welding. However, low heat input easily forms columnar crystals, which will endanger the mechanical properties of joints. Therefore, ultrasonication treatment was applied to the cold metal transfer welding of 304 stainless steel to conduct cold metal transfer welding assisted with ultrasonication in this paper. The comparison between cold metal transfer welding assisted with ultrasonication and cold metal transfer showed that the weld grain diameter obtained by cold metal transfer welding assisted with ultrasonication was finer. In the welded joint, the maximum grain size diameter of the weld seam in cold metal transfer welding assisted with ultrasonication decreased to 375 μm, and the maximum tensile strength of cold metal transfer welding assisted with ultrasonication increased to 734 MPa. The texture intensity of the weld seam in cold metal transfer was significantly greater than that of the weld seam in cold metal transfer welding assisted with ultrasonication, which was ascribed to the improvement of the microstructure of the weld seam in cold metal transfer welding assisted with ultrasonication. In cold metal transfer welding assisted with ultrasonication, the flow performance of the welding pool increased, and the ultrasonic cavitation degree was intensified. This resulted in the significant refinement of the weld grain, the reduction of texture intensity, and an increase in the tensile strength.

Development of polymorphic EST-SSR markers by sequence alignment in Frankliniella occidentalis (Pergande)

Jiani Liu,Zheng-Yue Li,Xiaoyan Chen,Heping Huang,Furong Gui 한국응용곤충학회 2014 Journal of Asia-Pacific Entomology Vol.17 No.3

The western flower thrips, Frankliniella occidentalis, is the most economically important agronomic pest withinThysanoptera because it is both a direct pest of horticulture crops and an efficient vector of plant viruses. Sixty-seven polymorphic SSR loci were identified in the contigs (containing redundant ESTs) generated byassembling 13,839 F. occidentalis ESTs from the public sequence database. Nineteen SSR markers exhibited polymorphismamong 860 samples from43 F. occidentalis populations,with alleles per SSR marker ranging fromtwoto eight, the effective number of alleles (Ne) range from 0.73 to 2.64; the observed (Ho) and expected (He) heterozygositiesranged from 0.09 to 0.77 and 0.12 to 0.96, respectively. The PIC values were from 0.24 to 0.73. AMOVA revealed most genetic variation resided within, rather than between, greenhouse and field isolates. The Mantel test showed no significant differences between genetic and geographical distances. We demonstratedthe value of mining the redundant sequences in public sequence databases for the development of polymorphicSSR markers, which can be used for better understanding population variation and spreading of the invasive pestF. occidentalis.

Glia maturation factor beta deficiency protects against diabetic osteoporosis by suppressing osteoclast hyperactivity

Shi Si,Gu Huijie,Xu Jinyuan,Sun Wan,Liu Caiyin,Zhu Tong,Wang Juan,Gao Furong,Zhang Jieping,Ou Qingjian,Jin Caixia,Xu Jingying,Chen Hao,Li Jiao,Xu Guotong,Tian Haibin,Lu Lixia 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Excessive osteoclast activation, which depends on dramatic changes in actin dynamics, causes osteoporosis (OP). The molecular mechanism of osteoclast activation in OP related to type 1 diabetes (T1D) remains unclear. Glia maturation factor beta (GMFB) is considered a growth and differentiation factor for both glia and neurons. Here, we demonstrated that Gmfb deficiency effectively ameliorated the phenotype of T1D-OP in rats by inhibiting osteoclast hyperactivity. In vitro assays showed that GMFB participated in osteoclast activation rather than proliferation. Gmfb deficiency did not affect osteoclast sealing zone (SZ) formation but effectively decreased the SZ area by decreasing actin depolymerization. When GMFB was overexpressed in Gmfb-deficient osteoclasts, the size of the SZ area was enlarged in a dose-dependent manner. Moreover, decreased actin depolymerization led to a decrease in nuclear G-actin, which activated MKL1/SRF-dependent gene transcription. We found that pro-osteoclastogenic factors (Mmp9 and Mmp14) were downregulated, while anti-osteoclastogenic factors (Cftr and Fhl2) were upregulated in Gmfb KO osteoclasts. A GMFB inhibitor, DS-30, targeting the binding site of GMFB and Arp2/3, was obtained. Biocore analysis revealed a high affinity between DS-30 and GMFB in a dose-dependent manner. As expected, DS-30 strongly suppressed osteoclast hyperactivity in vivo and in vitro. In conclusion, our work identified a new therapeutic strategy for T1D-OP treatment. The discovery of GMFB inhibitors will contribute to translational research on T1D-OP.