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Objective:To explore the influence of puerarin on pancreatic tissue let-7f and immune factors IL-17 and IL-23 expression of rats with gestational diabetes mellitus .Methods:120 cases of rats were divided into the normal control group ,the blank control group,simvastatin group,puerarin low-dose group,puerarin medium-dose group and puerarin high-dose group.The normal control group were given basal diet,and the other groups were given high fat diet ,all fed for two weeks.The simvastatin group were given 2 mg/kg simvastatin,and the puerarin group were given 70 mg/kg,120 mg/kg,170 mg/kg puerarin according to low ,medium,high dose,and the normal control group and blank control group were given the same amount of normal saline ,after 2 weeks of treatment , blood sugar and blood lipid and let-7f expression in pancreatic tissue of rats were tested in the six groups .Results:After treatment, FBG,TC,TG and FFA of rats in the simvastatin group and puerarin group were significantly lower than those in the blank control group , and with the increasing of puerarin dose ,the levels decreased significantly (P<0.05),in a dose-dependent manner.Let-7f expression in pancreatic tissue of the simvastatin group and puerarin group was significantly higher than that in the blank control group (P<0.05),in a dose-dependent manner .IL-17 and IL-23 expression in serum and pancreatic tissue of the simvastatin group and puerarin group was significantly higher than that of the blank control group ( P<0.05 ) ,in a dose-dependent manner .Conclusion:Puerarin can increase let-7f expression in pancreatic tissue of gestational diabetes mellitus rats with gestational diabetes mellitus ,and can reduce IL-17 and IL-23 expression in serum and pancreatic tissue .It can provide reference for clinical treatment of gestational diabetes mellitus .
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Objective To investigate the influence of Let-7f regulation on MMP-11 in migration and in-vasion of pancreatic cancer. Methods RT-qPCR was performed to assay the expression of Let7 and MMP-11 ex-pression in pancreatic cancer cells and normal pancreatic cells. Let-7f mimic and inhibitor were transfected to PANC-1 and Bx-PC3, respectively. The influence of Let-7f expression on migration and invasion of pancreatic cancer cells was analyzed by transwell. The influence of Let-7f intervention on MMP-11 expression was observed by RT-qPCR. Results Let-7f expression decreased in PANC-1 and Bx-PC3, compared to HPDE6c7, while MMP-11 expression up-regulated in PANC-1 and Bx-PC3 , compared to HPDE6c7 cells. Let-7f overexpression in-hibited the expression of MMP-11. Up-regulated Let-7f could significantly inhibit migration and invasion of PANC-1 and Bx-PC3 and Let-7f inhibitor enhanced MMP-11 expression. However , down-expression of Let-7f could not significantly promote migration and invasion abilities of PANC-1 and Bx-PC3cells. Conclusions Let-7f may affect migration and invasion by regulating MMP-11 expression in pancreatic cancer , suggesting that Let-7f might be a potential target for gene therapy in human pancreatic cancer.
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Aims: The expression of gene and gene product is typically inhibited by a small noncoding RNA (microRNA) or DNA methylation. The aim of this study is to investigate mechanisms involving microRNA let-7f by which the repeated cycles of ethanol exposure and withdrawal provoke mitochondrial respiratory damage. Study Design: The rat or cell model of repeated withdrawal from a high dose of ethanol exposure was used to mimic human alcoholics who repeat the cycles of heavy drinking and unsuccessful attempts at abstaining. Place and Duration of Study: Department of Pharmacology and Neuroscience University of North Texas Health Science Center at Fort Worth, between June 2011 and March 2014. Methodology: Male adult rats received an ethanol program, consisting of two cycles of ethanol exposure (4 weeks) and withdrawal (2 weeks). At the end of the ethanol program, one hemisphere of each rat was used to measure the level of let-7f using TaqMan let-7f primers and qPCR. The other hemisphere was used to measure the methylation of cytosine in let-7f gene using bisulfite conversion and pyrosequencing. Separately, HT22 cells (mouse hippocampal cells) were exposed to an ethanol program, consisting of two cycles of ethanol exposure (20 hours) and withdrawal (4 hours). During the entire ethanol program, the cells were treated with let-7f antagomir (inhibitor) or a methylation-inducing methyl-donor. The role of let-7f in mitochondria was assessed by quantifying a mitochondrial enzyme, cytochrome c oxidase-IV (COX subunit IV) and realtime mitochondrial respiration using an immunoblot method and XF respirometry, respectively. Results: The level of let-7f increased (2.4±0.5 fold increase), whereas the methylation of let-7f gene decreased in the brain of rats that underwent repeated ethanol exposure and withdrawal (called “repeated-ethanol/withdrawal”). The methyl-donor treatment completely abolished the increase in let-7f induced by repeated-ethanol/withdrawal. let-7f antagomir treatment also abolished the inhibiting effect of repeated-ethanol/withdrawal on COX-IV and mitochondrial respiration. Conclusion: These data suggest that repeated-ethanol/withdrawal provokes the dysregulation of let-7f, thereby damaging brain mitochondria. Mitochondria-associated microRNA may be a potential research and drug target to manage alcoholism.