Fei H.,Taishan Medical University |
Zhou Y.,Central Hospital of Taian |
Li R.,Taishan Medical University |
Yang M.,Taishan Medical University |
And 2 more authors.
Cell Cycle | Year: 2017
To maintain the integrity of the genome, cells need to detect and repair DNA damage before they complete cell division. Hepatitis B x-interacting protein (HBXIP), a binding protein of HBx (Hepatitis B virus × protein), is aberrantly overexpressed in human cancer cells and show to promote cell proliferation and inhibit apoptosis. The present study is designed to investigate the role of HBXIP on the DNA damage response. Our results show that HBXIP acts as an important regulator of G2/M checkpoint in response to DNA damage. HBXIP knockdown increases phospho-histone H2AX expression and foci formation after treatment with ionizing radiation (IR). HBXIP regulates the ATM-Chk2 pathway following DNA damage. Depletion of HBXIP abrogates IR-induced G2/M cell cycle checkpoints, accompanying decrease the expression of phospho-Cdc25C, phospho-Cdc2 (Tyr15) and p27. We also show that downregulation of HBXIP expression sensitizes cancer cells to chemotherapy, as evidenced by an increase in apoptosis and cleavage of caspase-3 and caspase-9. Our data suggest that HBXIP can function as a mediator protein for DNA damage response signals to activate the G2/M checkpoint to maintain genome integrity and prevent cell death. © 2017 Taylor & Francis
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.
Chen T.-Z.,Shandong University |
Chen T.-Z.,Taishan Medical University |
Xu G.-J.,Taishan Medical University |
Zhou G.-A.,Central Hospital of Taian |
And 3 more authors.
Brain Research | Year: 2014
There is compelling evidence that postural instability occurs at very early clinical stages of Parkinsons disease (PD), making it tempting to speculate that changes in postural sway may even occur at a prodromal phase. Studies estimate that approximately half of patients with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) will eventually develop PD, so RBD may be an indicator of prodromal PD. This study was undertaken to investigate postural sway and its relation to stereopsis function in patients with RBD. We examined 24 patients with polysomnography-confirmed RBD and 23 healthy, sex-and age-matched control subjects. Postural sway was measured with an accelerometer at the center of mass at the lower spine. Subjects were asked to stand quietly for 30 s under two usual conditions (eyes open and eyes closed) and three challenging conditions (eyes open with dual task, eyes closed with dual task, and tandem standing). Stereopsis was assessed using the Titmus fly test. RBD patients showed an increased variability of trunk acceleration and a decrease of smoothness of sway, compared to control subjects. These differences reached significance in the challenging conditions. RBD patients demonstrated significant impairment in stereopsis. There were statistically significant correlations between log seconds of arc of the Titmus test and some sway parameters within the RBD group. RBD patients with abnormal stereopsis showed a significant increase of JERK values compared to patients with normal stereopsis in the challenging conditions. Our results indicate that idiopathic RBD patients, especially with abnormal stereopsis, have subtle signs of postural instability under challenging conditions. Postural sway performance may serve as a biological marker for prodromal PD. © 2014 Elsevier B.V.
Zhang W.-L.,Yantaishan Hospital |
Yan W.-J.,Central Hospital of Taian |
Sun B.,Yantaishan Hospital |
Zou Z.-P.,Hospital of Economic and Technological Development Zone
Lipids in Health and Disease | Year: 2014
Background: Endothelial dysfunction is implicated in the initiation and progression of atherosclerosis. Whether atorvastatin combined with rosiglitazone has synergistic effects on endothelial function improvement in the setting of dyslipidemia is unknown. Methods: Dyslipidemia rat model was produced with high-fat and high-cholesterol diet administration. Thereafter, atorvastatin, rosiglitazone or atorvastatin combined with rosiglitazone were prescribed for 2 weeks. At baseline, 6 weeks of dyslipidemia model production, and 2 weeks of medical intervention, fasting blood was drawn for parameters of interest evaluation. At the end, myocardium was used for 15-deoxy-delta-12,14-PGJ2 (15-d-PGJ2) assessment. Results: Initially, there was no significant difference of parameters between sham and dyslipidemia groups. With 6 weeks' high-fat and high-cholesterol diet administration, as compared to sham group, serum levels of triglyceride (TG), total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) were significantly increased. Additionally, nitric oxide (NO) production was reduced and serum levels of malondialdehyde (MDA), C-reactive protein (CRP) and asymmetric dimethylarginine (ADMA) were profoundly elevated in dyslipidemia group. After 2 weeks' medical intervention, lipid profile was slightly improved in atorvastatin and combined groups as compared to control group. Nevertheless, in comparison to control group, NO production was profoundly increased and serum levels of MDA, CRP and ADMA were significantly decreased with atorvastatin or rosiglitazone therapy. 15-d-PGJ2 expression of myocardium was also significantly elevated with atorvastatin or rosiglitazone treatment. Notably, these effects were further enhanced with combined therapy, suggesting that atorvastatin and rosiglitazone had synergistic effects on endothelial protection, and inflammation and oxidation amelioration. Conclusion: Atorvastatin and rosiglitazone therapy had synergistic effects on endothelium protection as well as amelioration of oxidative stress and inflammatory reaction in rats with dyslipidemia.
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.
Jiang M.,Central Hospital of Taian |
Zhang Z.,Taishan Medical University |
Zhao S.,Central Hospital of Taian
Polish Journal of Microbiology | Year: 2014
Multidrug-resistant Acinetobacter baumannii is an important bacterium causing nosocomial infections; A. baumannii infections have increased in our hospital since 2009. However, multidrug-resistant A. baumannii, which was mainly isolated from patients in each intensive care unit (ICU), rapidly increased from December 2012 to January 2013. Therefore, we described the molecular characteristics of A. baumannii by pulsed-field gel electrophoresis (PFGE). We also detected resistance genes for β-lactam, aminoglycosides, and plasmid-mediated quinolones. Disinfectant-resistant genes were also detected in the clinical isolates of blaOXA-51-positive multidrug-resistant A. baumannii. The conjugative test was performed to detect whether or not resistance genes can be transferred to different strains. Carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibition test was conducted to analyze the factors influencing the resistance of A. baumannii to imipenem, meropenem, ceftazidime, levofloxacin, and tigecycline. PFGE profiles contained 12 strains, including 20 type C strains (47.6%), 4 type D strains (9.5%), and 1 to 3 strains of other types; 38 strains were distributed in patients in each ICU. In our test samples, the presence of blaOXA-23 was closely related to carbapenem resistance. The 16S rRNA methylase gene armA was associated with resistance to amikacin, gentamicin, and tobramycin. The multidrug-resistant A. baumannii was closely related to various resistance genes. These results indicated that multidrug-resistant A. baumannii with type C strains was predominant in our hospital in this period.
Kong L.,Beijing Jiaotong University |
Meng Q.,Central Hospital of Taian
Mathematical Methods of Operations Research | Year: 2012
In this paper, we employ the projection operator to design a semismooth Newton algorithm for solving nonlinear symmetric cone programming (NSCP). The algorithm is computable from theoretical standpoint and is proved to be locally quadratically convergent without assuming strict complementarity of the solution to NSCP. © Springer-Verlag 2012.
Li G.,Shandong University |
Li G.,Central Hospital of Taian |
Liu T.,Beijing University of Chinese Medicine |
Kong X.,Shandong University |
And 2 more authors.
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.
Gao X.-Y.,Central Hospital of Taian |
Wang X.-L.,Central Hospital of Taian
Journal of B.U.ON. | Year: 2015
Purpose: Colon cancer is one of the most common malignancies worldwide. Cancer stem-like cells (CSCs) are a distinct subgroup of cancer cells that play a vital role in the development of cancer and also a role in the development of resistance against therapeutic agents. In this study we investigated the role of CSCs in colon cancer and evaluated the tumor-associated antigen CEP55 for targeting immunotherapeutically CSCs. Methods: Side population (SP) cells from colon cancer cell line SW480, were isolated using DNA-binding dye Hoechst 33342. The cytotoxic activity of cytotoxic T lymphocytes (CTL) clone 41 for side population (SP) cells and main population (MP) cells was evaluated using 51Cr release assay. The SP cells, MP cells and presorted cells from the colon cancer cell line were evaluated in NOD/SCID mice. Results: The isolated SP cells showed resistance to the chemotherapeutic agents irinotecan and oxaliplatin, which suggests that targeting the CSCs can be a better strategy for the treatment of chemotherapy-resistant colon cancer. HLA class I and HLA-A24 in SP cells and MP cells were expressed at the same level. We used CTL clone 41 to corroborate the sensitivity of SP cells to cytotoxic T lymphocyte response. The cytotoxic responses of SP cells were to the same extent as they were in MP cells and presorted cells. Adoptive transfer of CTL clone 41 in immunodeficient mice inhibited SW480-induced tumors, suggesting that this approach can be used for colon cancer immunotherapy. Conclusion: Our novel findings suggest that colon cancer CSCs are sensitive to CTLs, and CEP55, a tumor-associated antigen, can be successfully used as active immunotherapy for targeting CSCs in colon cancer.