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Yan C.,Nanjing Medical University | Kong D.,Shanghai JiaoTong University | Ge D.,Central Hospital of Taian | Zhang Y.,Affiliated Hospital of Taishan Medical College | And 3 more authors.
Cellular Physiology and Biochemistry | Year: 2015

Background/Aims: Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterised by prominent synoviocyte hyperplasia and a potential imbalance between the growth and death of fibroblast-like synoviocytes (FLS). Mitomycin C (MMC) has previously been demonstrated to inhibit fibroblast proliferation and to induce fibroblast apoptosis. However, the effects of MMC on the proliferation and apoptosis of human RA FLS and the potential mechanisms underlying its effects remain unknown. Methods: Cell viability was determined using the Cell Counting Kit-8 assay. Apoptotic cell death was analysed via Annexin V-FITC/PI double staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling. The production of intracellular reactive oxygen species (ROS) was assessed via flow cytometry, and the changes in mitochondrial membrane potential (ΔΨm) were visualized based on JC-1 staining via fluorescence microscopy. The expression of apoptosis-related proteins was determined via Western blot. Results: Treatment with MMC significantly reduced cell viability and induced apoptosis in RA FLS. Furthermore, MMC exposure was found to stimulate the production of ROS and to disrupt the ΔΨm compared to the control treatment. Moreover, MMC increased the release of mitochondrial cytochrome c, the ratio of Bax/Bcl-2, the activation of caspase-9 and caspase-3, and the subsequent cleavage of poly(ADP-ribose) polymerase. Conclusion: Our findings suggest that MMC inhibits cell proliferation and induces apoptosis in RA FLS, and the mechanism underlying this MMC-induced apoptosis may involve a mitochondrial signalling pathway. © 2015 S. Karger AG, Basel.

Liu J.,Jilin University | Han J.,Central Hospital of Taian | Kang Z.,Jilin University | Golamaully R.,Jilin University | And 3 more authors.
Nanoscale | Year: 2014

Photothermal therapy, as a physical therapeutic technique to kill cancer, has generated a great deal of interest. Photothermal agents hence play a critical role in this modern therapy. We report the use of transition metal oxides as photothermal agents based on PEGylated WO3-x nanoparticles. The well-prepared nanoparticles presented effective results during photothermal therapy both in vitro and in vivo by using near-IR laser irradiation (980 nm, 0.5 W cm-2). The tumor cells were effectively damaged using low power density during a short irradiation time without destroying healthy tissues. In vitro results of photothermal therapy with PEGylated WO3-x nanoparticles proved to be effective on 4T1 murine breast cancer cells via a confocal microscopy method and MTT assay. In vivo results were further confirmed by hematoxylin and eosin (H & E) histological staining. Additionally, PEGylated WO3-x nanoparticles were shown to be effective as a CT imaging contrast agent on a tumor-bearing mouse model. Our results suggest that this generation of PEGylated WO3-x nanoparticles can potentially be used in oncological CT imaging and photothermal therapy. © 2014 the Partner Organisations.

Li G.,Shandong University | Liu T.,Beijing University of Chinese Medicine | Kong X.,Shandong University | Wang L.,Central Hospital of Taian | Jin X.,Shandong University
Journal of Molecular Neuroscience | Year: 2014

Cdk5 is a member of cyclin-dependent kinase (Cdk), a proline-directed serine/threonine kinase, and plays a key role in normal neural development and function. Evidence of previous study showed that chronic inhibition of Cdk5 in hippocampal dentate gyrus (DG) blocked the development of depressive-like symptoms, suggesting that Cdk5 plays a role in development of depression. Forced swim test, novelty-suppressed feeding test, and learned helplessness were used to evaluate the cellular and molecular mechanisms underlying the behavioral regulation of Cdk5 inhibitors in rats. Two Cdk5 inhibitors butyrolactone and roscovitine were used to investigate the possible antidepressant-like actions of Cdk5 blockade and the potential mechanisms. Systemic administration of butyrolactone (200 mg/kg, IP) or roscovitine (100 mg/kg, IP) produced effective antidepressant-like actions. Moreover, infusion (5 mM) of GSK3β activator LY294002 into DG abolished the antidepressant-like actions of butyrolactone and roscovitine, suggesting that inhibition of GSK3β might be involved in the antidepressant effect of Cdk5 inhibitors. Moreover, pretreatment of LY294002 (5 mM) blocked the antidepressant-like effect of butyrolactone and roscovitine in learned helplessness. Additionally, inescapable footshock induced a significant increase of GSK3β activity, while butyrolactone and roscovitine decreased GSK3β activity. In contrast, pretreatment of LY294002 prevented the inhibitory effects of butyrolactone and roscovitine on GSK3β activation. Finally, a specific GSK3β inhibitor, SB216763 (1 ng, DG), demonstrated an effective antidepressant-like action. These findings demonstrate that systemic administration of Cdk5 inhibitors produced antidepressant-like actions and that inhibition of GSK3β is involved in behavioral response of Cdk5 inhibitors. © 2014 Springer Science+Business Media.

Duan Y.,Shandong University | Duan Y.,Taishan University | Nie J.,Central Hospital of Taian | Zhang Z.,Taishan University | Ji C.,Shandong University
Blood Coagulation and Fibrinolysis | Year: 2015

A 52-year-old woman was admitted to the hospital three times in a span of 5 years in hypovolemic shock because of spontaneous and massive bleeding in the pleural and abdominal cavity. Blood tests revealed a high number of blood cells, and bone marrow smears showed trilineage myeloproliferation. Serum erythropoietin level was decreased. Analysis revealed a V617F mutation in the JAK2 protein. Her activated partial thromboplastin time was slightly prolonged, the ratio between von Willebrand factor (vWF) propeptide and vWF antigen was in the normal range, but the ratio between vWF and ristocetin cofactor was decreased dramatically. Further investigation revealed the absence of large and intermediate vWF-multimers. She was diagnosed with polycythemia vera with acquired von Willebrand syndrome. The bleeding was stopped using a transfusion of freshly thawed plasma and cryoprecipitate. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Jiao P.,Taishan Medical University | Zhou Y.-S.,Central Hospital of Taian | Yang J.-X.,Shandong Institute of Pomology | Zhao Y.-L.,Taishan Medical University | And 3 more authors.
Molecular and Cellular Biochemistry | Year: 2013

It has become evident that AKT inhibitors have great potential in cancer treatment. In this study, we investigate the anticancer activity of MK-2206, a novel AKT inhibitor, on HepG2 hepatocellular carcinoma cell, and to show whether MK-2206 enhances the apoptosis-inducing potential of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The cell growth inhibition was evaluated by MTT assay and colony formation assay. Cell cycle distribution was assessed by propidium iodide flow cytometry. Apoptosis was determined by AnnexinV-FITC/PI double staining assay and caspase-9, casapse-7, caspase-3, and PARP cleavage. The results of present study showed that MK-2206-induced G1-phase arrest was associated with a marked decrease in the protein expression of cyclin D1 with concomitant induction of p21 and p27. MK-2206-induced apoptosis was characterized by cleavage of a pro-caspase in a concentration-dependent manner. Moreover, the MAP family kinases p38 kinase and JNK were activated by exposure to MK-2206. SB203580, an p38-specific inhibitor, partially blocked MK-2206-induced death of HepG2 cells and caspase activation. A combination of MK-2206 with TRAIL significantly inhibited growth of TRAIL resistant HepG2 cells. Taken together, our findings provide a new insight to better understand anticancer mechanisms of MK-2206, at least in HepG2 cell. Using of MK-2206 as a potent sensitizer to TRAIL-induced apoptotic cell death offers a promising means of enhancing the efficacy of TRAIL-based HCC treatments. © 2013 Springer Science+Business Media New York.

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