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      • KCI등재

        MicroRNA-375 is a therapeutic target for castration-resistant prostate cancer through the PTPN4/STAT3 axis

        Gan Junqing,Liu Shan,Zhang Yu,He Liangzi,Bai Lu,Liao Ran,Zhao Juan,Guo Madi,Jiang Wei,Li Jiade,Li Qi,Mu Guannan,Wu Yangjiazi,Wang Xinling,Zhang Xingli,Zhou Dan,Lv Huimin,Wang Zhengfeng,Zhang Yanqiao,Q 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

        The functional role of microRNA-375 (miR-375) in the development of prostate cancer (PCa) remains controversial. Previously, we found that plasma exosomal miR-375 is significantly elevated in castration-resistant PCa (CRPC) patients compared with castration-sensitive PCa patients. Here, we aimed to determine how miR-375 modulates CRPC progression and thereafter to evaluate the therapeutic potential of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes loaded with miR-375 antisense oligonucleotides (e-375i). We used miRNA in situ hybridization technique to evaluate miR-375 expression in PCa tissues, gain- and loss-of-function experiments to determine miR-375 function, and bioinformatic methods, dual-luciferase reporter assay, qPCR, IHC and western blotting to determine and validate the target as well as the effects of miR-375 at the molecular level. Then, e-375i complexes were assessed for their antagonizing effects against miR-375. We found that the expression of miR-375 was elevated in PCa tissues and cancer exosomes, correlating with the Gleason score. Forced expression of miR-375 enhanced the expression of EMT markers and AR but suppressed apoptosis markers, leading to enhanced proliferation, migration, invasion, and enzalutamide resistance and decreased apoptosis of PCa cells. These effects could be reversed by miR-375 silencing. Mechanistically, miR-375 directly interfered with the expression of phosphatase nonreceptor type 4 (PTPN4), which in turn stabilized phosphorylated STAT3. Application of e-375i could inhibit miR-375, upregulate PTPN4 and downregulate p-STAT3, eventually repressing the growth of PCa. Collectively, we identified a novel miR-375 target, PTPN4, that functions upstream of STAT3, and targeting miR-375 may be an alternative therapeutic for PCa, especially for CRPC with high AR levels.

      • SCISCIESCOPUS

        Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes.

        Li, Tiangang,Chanda, Dipanjan,Zhang, Yanqiao,Choi, Hueng-Sik,Chiang, John Y L American Society for Biochemistry and Molecular Bi 2010 Journal of lipid research Vol.51 No.4

        <P>Bile acids play important roles in the regulation of lipid, glucose, and energy homeostasis. Recent studies suggest that glucose regulates gene transcription in the liver. The aim of this study was to investigate the potential role of glucose in regulation of bile acid synthesis in human hepatocytes. High glucose stimulated bile acid synthesis and induced mRNA expression of cholesterol 7alpha-hydroxylase (CYP7A1), the key regulatory gene in bile acid synthesis. Activation of an AMP-activated protein kinase (AMPK) decreased CYP7A1 mRNA, hepatocyte nuclear factor 4alpha (HNF4alpha) protein, and binding to CYP7A1 chromatin. Glucose increased ATP levels to inhibit AMPK and induce HNF4alpha to stimulate CYP7A1 gene transcription. Furthermore, glucose increased histone acetylation and decreased H3K9 di- and tri-methylation in the CYP7A1 chromatin. Knockdown of ATP-citrate lyase, which converts citrate to acetyl-CoA, decreased histone acetylation and attenuated glucose induction of CYP7A1 mRNA expression. These results suggest that glucose signaling also induces CYP7A1 gene transcription by epigenetic regulation of the histone acetylation status. This study uncovers a novel link between hepatic glucose metabolism and bile acid synthesis. Glucose induction of bile acid synthesis may have an important implication in metabolic control of glucose, lipid, and energy homeostasis under normal and diabetic conditions.</P>

      • KCI등재

        Ultramini nephrostomy tract combined with flexible ureterorenoscopy for the treatment of multiple renal calculi in paediatric patients

        Jingyang Guo,Wen Zeng Yang,Yanqiao Zhang,Feng An,Ruojing Wei,Yu Li,Haisong Zhang 대한비뇨의학회 2015 Investigative and Clinical Urology Vol.56 No.7

        Purpose: To assess the safety and efficacy of an ultramini nephrostomy tract, which we were using for the first time, combinedwith flexible ureterorenoscopy (URS) in the treatment of pediatric patients with multiple renal calculi. Materials and Methods: Twenty pediatric patients (age, ≤6 years) underwent ultramini percutaneous nephrolithotomy (PCNL)combined with flexible URS. The group had multiple renal calculi, which were bilateral in 3 cases and were located in a total of 23sites. The calculi were located in 2 calyces in 10 cases, scattered in more than 2 calyces in 7 cases, and limited to 1 calyx in 3 cases. The average patient age was 37.35 months (range, 14–68 months). The average stone diameter was 2.0 cm (range, 1–3.0 cm). Inall patients, an ultramini nephrostomy tract was established under ultrasound guidance (dilated to F10) with simultaneous sheathplacement. The flexible URS was placed into the collecting system during holmium laser lithotripsy. Results: When ultramini PCNL was combined with flexible ureterorenoscopic holmium laser lithotripsy, the complete stone-freerate was 87% (20/23). The average level of hemoglobin decreased to 1.0 g/dL after the operation. No blood transfusions wereneeded. Levels of blood urea nitrogen, creatinine, and C-reactive protein were not significantly different before and after the operation. The average duration of hospitalization was approximately 4.85 days, and all cases were followed up for 6 to 12 months. No complications were found. Conclusions: Ultramini PCNL combined with flexible ureterorenoscopic holmium laser lithotripsy is a safe and effective treatmentfor children with multiple renal calculi.

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