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Yang L.,The Peoples Hospital of Jilin Province | He J.-T.,Jilin University | Guan H.,The Peoples Hospital of Jilin Province | Sun Y.-D.,The Peoples Hospital of Jilin Province
Asian Pacific Journal of Cancer Prevention

AKT1 is a member of the serine/threoine AGC protein kinase family involved in thyroid cancer metabolism, growth, proliferation and survival. It is overexpressed in thyroid tumors. In this study, we designed two AKT1 specific DNAzymes (DRz1 and DRz2) that target AKT1 mRNA. The results showed that DRz1 could decrease the expression of AKT1 by 58%. Furthermore, DRz1 significantly inhibited cell proliferation, induced apoptosis and inhibited invasion in SW597 cells. In addition, down-regulation of survivin expression was associated with decreased caspase-3, VEGF and MMP2 in SW597 cells after 24 h. In our study, the efficacy of DRz1 in decreasing AKT1 protein levels were better than DRz2. AKT1-DRz1 might have anti-tumorigenic activity and may provide the basis for a novel therapeutic intervention in thyroid cancer treatment. Source

Liu X.,Jilin University | Ye F.,Mount Sinai School of Medicine | Xiong H.,Mount Sinai School of Medicine | Hu D.-N.,Tissue Culture Center | And 12 more authors.
Experimental Cell Research

IL-6 plays an important role in various inflammatory ocular diseases, including diabetic retinopathy. Müller cells are the major source of inflammatory mediators, including IL-6, in the retina. However, the mechanism of regulating IL-6 production in these cells remains unclear. Examination of signaling pathways in human retinal Müller cells (MIO-M1 cell line) cultured with IL-1β, TNF-α, IL-6, IL-8, VEGF, IFN-γ, glucose or mannitol showed that IL-1β was the most potent stimulator of IL-6 production. In addition, IL-1 β also increased NF-κB p50 protein level and phosphorylation of p38 MAPK, ERK1/2 and c-Jun. Induction of IL-6 production by IL-1β was significantly reduced by addition of p38 MAPK (SB203580), MEK1/2 (U0126) or NF-κB (BAY11-7082) inhibitors, with the highest effect being observed with SB203580. To explore the specific elements in IL-6 promoter responsible for IL-1β-induction of IL-6 expression, a series of plasmids bearing various IL-6 promoter mutations were transiently expressed in MIO-MI cells cultured in the presence or absence of IL-1β (10. ng/ml) and/or SB203580 (10. μM). Results showed that IL-6 promoter activity of the parent pIL-6-Luc651 was significantly enhanced by IL-1β, but the level was significantly attenuated by SB203580. Furthermore, the IL-6 promoter activity was also reduced upon deletion of NF-κB, AP-1 or C/EBP binding sites, with NF-κB deletion being the greatest. These results are the first demonstration that IL-1β induces IL-6 production in Müller cells by activation of IL-6 promoter activity predominantly through the p38 MAPK/NF-κB pathway. © 2014 Elsevier Inc. Source

Cong X.-Q.,Jilin University | Li Y.,The Peoples Hospital of Jilin Province | Zhao X.,Jilin University | Dai Y.-J.,The Friendship Hospital of Linjiang | Liu Y.,Jilin University
Journal of Cardiovascular Translational Research

Bone marrow stem cells (BMSCs) have been used to treat patient with ST-segment elevation myocardial infarction (STEMI) via intracoronary route. We performed a meta-analysis to evaluate the short-term efficacy and safety of this modality. Seventeen randomized controlled trials (RCTs) of BMSC-based therapy for STEMI, delivered with 9 days of reperfusion and followed up shorter than 12 months, were identified by systematic review. Intracoronary BMSC therapy resulted in an overall significant improvement in left ventricular ejection fraction (LVEF) by 2.74 % (95 % confidence interval (CI) 2.09–3.39, P < 0.00001, I2 = 84 %) at 3–6-month follow-up and 5.1 % (95 % CI 4.16–6.03, P < 0.00001 and I2 = 85 %) at 12 months. The left ventricular end-systolic volume (LVESV) and wall motion score index (WMSI) were also reduced at 3–6 months. At 12 months, left ventricular end-diastolic volume (LVEDV), LVESV, and WMSI were significantly reduced in BMSC group. In conclusion, intracoronary BMSC therapy at post-STEMI is safe and effective in patient with acute STEMI. © 2015, Springer Science+Business Media New York. Source

Cong X.-Q.,Jilin University | Piao M.-H.,Jilin University | Li Y.,The Peoples Hospital of Jilin Province | Xie L.,Jilin University | Liu Y.,Jilin University
Biological Trace Element Research

Endoplasmic reticulum stress (ERS)-induced unfolded protein response (UPR) and the subsequent cell deaths are essential steps in the pathogenesis of diabetic cardiomyopathy (DCM), a main cause of diabetics’ morbidity and mortalities. The bis(maltolato)oxovanadium(IV) (BMOV), a potent oral vanadium complex with anti-diabetic properties and insulin-mimicking effects, was shown to improve cardiac dysfunctions in diabetic models. Here, we examined the effects of BMOV on UPR pathway protein expression and apoptotic cell deaths in both high glucose-treated cardiac H9C2 cells and in the hearts of diabetic rats. We show that in both the high glucose-treated cardiac cells and in the hearts of streptozotocin (STZ) diabetic rats, there was an overall activation of the UPR signaling, including both apoptotic (e.g., the cascades of PERK/EIf2α/ATF4/CHOP and of IRE1/caspase 12/caspase 3) and pro-survival (GRP78 and XBP1) signaling. A high amount of apoptotic cell deaths was also detected in both diabetic conditions. The administration of BMOV suppressed both the apoptotic and pro-survival UPR signaling and significantly attenuated apoptotic cell deaths in both conditions. The overall suppression of UPR signaling by BMOV suggests that the drug protects diabetic cardiomyopathy by counteracting reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress. Our findings lend support to promote the use of BMOV in the treatment of diabetic heart diseases. © 2016 Springer Science+Business Media New York Source

Liu X.,Jilin University | Ye F.,Mount Sinai School of Medicine | Xiong H.,Mount Sinai School of Medicine | Hu D.,Tissue Culture Center | And 8 more authors.

Diabetic retinopathy shares some similarity with chronic inflammation and Müller cells dysfunction may play an important role in its initiation and progression since these cells are thought to be a major source of inflammatory factors. The goal of this study was to examine the effect of cytokines on human retinal Müller cells and to understand the underlying signal transduction pathways regulating interleukin-8 (IL-8) expression. In this study, human MIO-M1 cells were treated with interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-8, vascular endothelial growth factor (VEGF), interferon-gamma (IFN-γ), glucose, or mannitol, followed by examination of their IL-8 protein and mRNA levels by Western blotting and PCR, respectively. After treatment with IL-1β, the levels of phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) were measured. IL-8 was also measured by Western blotting and ELISA following Müller cell culture with IL-1β and specific inhibitors of the p38 MAPK, ERK1/2, JNK, or JAK2 pathways. The results showed that IL-1β was a potent inducer of IL-8 expression in MIO-M1 cells, although a relatively small increase was induced by TNF-α. IL-6, IL-8, VEGF, and IFN-γ did not modify IL-8 expression. Increase of IL-8 expression was accompanied by a significant increased phosphorylation of p38 MAPK, ERK, and JNK, but not of JAK2 and STAT3. Furthermore, inhibitors of p38 MAPK and MEK1/2, but not for JNK and JAK2, significantly inhibited IL-8 expression. In conclusion, IL-1β potently stimulates IL-8 expression in Müller cells mainly through the p38 MAPK and ERK1/2 pathways. © 2014, Springer Science+Business Media New York. Source

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