ROCK1 induces dopaminergic nerve cell apoptosis via the activation of Drp1-mediated aberrant mitochondrial fission in Parkinson’s disease

Qian Zhang,Changpeng Hu,Jingbin Huang,Wuyi Liu,Wenjing Lai,Faning Leng,Qin Tang,Yali Liu,Qing Wang,Min Zhou,Fangfang Sheng,Guobing Li,Rong Zhang 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Dopamine deficiency is mainly caused by apoptosis of dopaminergic nerve cells in the substantia nigra of themidbrain and the striatum and is an important pathologic basis of Parkinson’s disease (PD). Recent research has shownthat dynamin-related protein 1 (Drp1)-mediated aberrant mitochondrial fission plays a crucial role in dopaminergicnerve cell apoptosis. However, the upstream regulatory mechanism remains unclear. Our study showed that Drp1knockdown inhibited aberrant mitochondrial fission and apoptosis. Importantly, we found that ROCK1 was activated inan MPP+-induced PD cell model and that ROCK1 knockdown and the specific ROCK1 activation inhibitor Y-27632blocked Drp1-mediated aberrant mitochondrial fission and apoptosis of dopaminergic nerve cells by suppressing Drp1dephosphorylation/activation. Our in vivo study confirmed that Y-27632 significantly improved symptoms in a PDmouse model by inhibiting Drp1-mediated aberrant mitochondrial fission and apoptosis. Collectively, our findingssuggest an important molecular mechanism of PD pathogenesis involving ROCK1-regulated dopaminergic nerve cellapoptosis via the activation of Drp1-induced aberrant mitochondrial fission.

Some Observations of the Influence Factors on the Response of Pile Groups

Qian-qing Zhang,Shi-min Zhang,Fayun Liang,Qian Zhang,Fei Xu 대한토목학회 2015 KSCE JOURNAL OF CIVIL ENGINEERING Vol.19 No.6

A simplified approach for nonlinear analysis of the load-displacement response of pile groups embedded in multilayered soils is presented in this work. A hyperbolic model is used to capture the relationship between unit skin friction and pile-soil relative displacement developed along the pile-soil interface and the stress-displacement relationship developed at the pile end. Considering interactive effect among piles, the parameters related to the hyperbolic model of an individual pile in a group can be computed. As to the analysis of the response of pile groups, a highly effective iterative computer program is developed using the hyperbolic model of an individual pile in a group. The efficiency and accuracy of the present method is verified using a well-documented field test. Furthermore, a parametric study is conducted to capture the influence of pile spacing and number of piles on the load-settlement response of the pile groups connected to a rigid cap. The pile-group settlement ratio and the pile-group resistance ratio are analyzed to assess the interaction effect among individual piles.

Historical Long-term Exposure to Pentachlorophenol Causing Risk of Cancer - A Community Study

Zheng, Rui-Zhi,Zhang, Qing-He,He, Yi-Xin,Zhang, Qian,Yang, Lin-Shen,Zhang, Zhi-Hua,Zhang, Xiu-Jun,Hu, Jing-Ting,Huang, Fen Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.2

Background: Pervious studies suggested occupational workers exposure to pentachlorophenol (PCP) might contribute to increased risk of cancer. However, few studies have focused on associations between PCP and cancer risk at the community level. Objective: The present study was to explore the cancer risk for the community population living long-term in a PCP contaminated area. Methods: All the cancer cases diagnosed in 2009-2011 in Tongling City were collected. The cancer patients' residencies were geo-referenced in each district. The historical PCP usage for each district of Tongling was calculated as the PCP pollution index, which was further used to divide into PCP exposure categories. Standardized rate ratios (SRRs) of cancer incidence were applied to detect the cancer risk as exposure grade elevated. Correlation analysis was performed to analyze the relationship between PCP pollution and cancer incidence. Results: A total of 5,288 cancer cases (3,451 male and 1,837 female) were identified. PCP usage was correlated with the incidence of leukemia (r=0.88, P=0.002) for males, and with cancer of the esophagus for males (r=0.83, P=0.008) and females (r=0.71, P=0.020). Compared with the low exposure category, significant SRRs for total cancer sites was obtained for high PCP exposure category (SRR=1.61, 95%CI=1.59-1.62). Most SRR values of the cancer sites were significantly increased as exposure grade elevated and exposure time extended. Conclusion: The present study found that community residents living in the PCP contaminated area had increased risk of cancers. Leukemias, lymphomas and nasopharyngeal and esophageal cancers are most possibly associated with PCP exposure.

Effects of injection rate on combustion and emissions of a pilot ignited direct injection natural gas engine

Qian Wang,Changsheng Shao,Qing Liu,Zhourong Zhang,Zhixia He 대한기계학회 2017 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.31 No.4

Effects of Injection rates on combustion process and emissions of engines operating with directly injected natural gas and pilot diesel were numerically investigated. Injection rates of natural gas and diesel were investigated separately utilizing five types of injection rates. An impact factor was defined to present the effects of the initial and terminal injection rates of diesel and natural gas on the combustion and emissions more intuitionally. Based on the simulation results, cylinder pressure and temperature were more sensitive to terminal injection rates of pilot diesel than initial injection rates, and lower terminal injection rates of pilot diesel can achieve lower NO and Soot emission level. However, there is a trade-off between NO and Soot emissions affected by different natural gas injection rates. The impact factors of pilot diesel injection rates on pressure show a double-peak trend. However, the impact factors of natural gas injection rates on pressure show a single-peak trend.

Antitumor Activity of Chloroquine in Combination with Cisplatin in Human Gastric Cancer Xenografts

Zhang, Hui-Qing,Fang, Nian,Liu, Xiao-Mei,Xiong, Shu-Ping,Liao, Yu-Qian,Jin, Wen-Jian,Song, Rong-Feng,Wan, Yi-Ye Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Purpose: To investigate the antitumor activity and mechanism of chloroquine (CQ) in combination with cisplatin (DDP) in nude mice xenografted with gastric cancer SGC7901 cells. Materials and Methods: 35 cases of gastric cancer patients with malignant ascites were enrolled and intraperitoneal cisplatin injection was performed. Ascites were collected before and 5 days after perfusion for assessment of autophagy levels in cancer cells. In addition, 24 tumor-bearing mice were randomly divided into control, DDP, CQ and CQ + DDP groups. Results: In 54.3% (19/35) of patients the treatment was therapeutically effective (OR), 5 days after peritoneal chemotherapy, 13 patients had the decreased ascites Beclin-1 mRNA levels. In 16 patients who had NR, only 2 cases had decreased Beclin-1 (P=0.001). Compared with the control group, the xenograft growth in nude mice in the DDP group was low, and the inhibition rate was 47.6%. In combination with chloroquine, the inhibition rate increased to 84.7% (P<0.01). The LC3-II/I ratio, and Beclin1 and MDR1/P-gp expression were decreased, while caspase 3 protein levels increased (P<0.05). Conclusions: Antitumor ability of cisplatin was associated with autophagy activity and chloroquine can enhance chemosensitivity to cisplatin in gastric cancer xenografts nude mice.

New Therapeutic Schedule for Prostatic Cancer-3 Cells with ET-1 RNAi and Endostar

Zhang, Hao-Jie,Qian, Wei-Qing,Chen, Ran,Sun, Zhong-Quan,Song, Jian-Da,Sheng, Lu Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

Background: Endothelin-1 and Endostar are both significant for the progression, proliferation, metastasis and invasion of cancer. In this paper, we studied the effect of ET-1 RNAi and Endostar in PC-3 prostatic cancer cells. Materials and Methods: The lentiviral vector was used in the establishment of ET-1 knockdown PC-3 cells. Progression and apoptosis were assessed by CKK-8 and flow cytometry, respectively. Transwell assay was used to estimate invasion and signaling pathways were studied by Western blotting. Results: ET-1 mRNA and protein in ET-1 knockdown PC-3 cells were reduced to 26.4% and 22.4% compared with control group, respectively. ET-1 RNAi and Endostar both were effective for the suppression of progression and invasion of PC-3 cells. From Western blotting results, the effects of ET-1 regulation and Endostar on PC-3 cells were at least related to some signaling pathways involving PI3K/Akt/Caspase-3, Erk1/2/Bcl-2/Caspase-3 and MMPs (MMP-2 and MMP-9). Furthermore, combined treatment of ET-1RNAi and Endostar was found to be more effective than single treatment. Conclusions: Both ET-1 RNAi and Endostar can inhibit the progression and invasion of PC-3 cells, but combined treatment might be a better therapeutic schedule.

Original Article: Food Science/Microbiology : Antioxidant and Antimicrobial Activities of Camellia Oleifera Seed Oils

( Qing Fen Zhou ),( Xue Jing Jia ),( Qian Qian Li ),( Rui Wu Yang ),( Li Zhang ),( Yong Hong Zhou ),( Chun Bang Ding ) 한국응용생명화학회(구 한국농화학회) 2014 Journal of Applied Biological Chemistry (J. Appl. Vol.57 No.2

The antioxidant and antimicrobial activities of Camellia oleifera seed oil were studied. Four kinds of seed oil samples were prepared, crude oil and refined oil, extracted by cold pressing method (CPC, CPR), and organic solvent extraction (OSC, OSR). Antioxidant activity analysis was measured in 2,2-azinobis (3- ethylbenzothiazoline-6-sulfonic acid)-diammonium salt, ferric reducing Ability of Plasma, and 2,2-diphenyl-1-picrylhydrazyl assays. Besides, the percentage of inhibition of red blood cells hemolysis induced by 2,2´-azobis(2-amidnopropane) dihydrochlorid, the lag time of LDL conjugated dienes formation in vitro, and the inhibitors of loss in tryptophan fluorescence were all used to estimate the antioxidant activity of the samples. The total phenolic contents (TPC) were detemined by Folin-Ciocalteu method. The TPC of the C. oleifera seed oils can be arranged in descending order: CPC (1.9172 μg/mL) > OSC (1.5218 μg/mL) > CPR (1.0611 μg/mL) > OSR (0.6782 μg/mL). And the oils were investigated for activity against Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae and Aspergillus niger. The results showed the antioxidant activity of crude oil by cold pressing method was stronger than others, and all oils did inhibit activity of the top three bacteria expert A. niger. The further significance of the study contributes to measure the antioxidant and antimicrobial activity of the potential health benefits by the different methods of preparation and the oil of C. oleifera seeds acting as free radical scavenger, pharmaceuticals and preservatives may offer some information in medicine and cosmetic not just in food field.

Xanthoceraside Induces Apoptosis in Melanoma Cells Through the Activation of Caspases and the Suppression of the IGF-1R/Raf/MEK/ERK Signaling Pathway

Qing Jiao,Libo Zou,Peng Liu,Qian Xu,Yifei Zhang,Ying Yu,Lu Zou,Tianyan Chi,Xuefei Ji 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.10

Xanthoceraside, a saponin extracted from the husks of Xanthoceras sorbifolia Bunge, suppresses inflammation and oxidative stress. However, the antitumor properties of xanthoceraside as well as its mechanism of action remain unclear. Therefore, we proposed to investigate its potential anticancer property. In this study, the viability of cells was measured by the MTT assay. Cell cycle and mitochondrial membrane potential were measured by flow cytometry, and the expressions of procaspase-9, procaspase-3, Cyto.c, Apaf-1, Bcl-2, Bcl-xL, Bad, p53, and IGF-1R/Raf/MEK/ERK were tested by Western blotting. Xanthoceraside significantly inhibited the proliferation of human melanoma A375.S2 cells in a concentration- and time-dependent manner but did not impair the viability of normal cells (peripheral blood mononuclear cells). Further analysis revealed that xanthoceraside induced apoptosis by activating caspase-3 and caspase-9 in a time-dependent manner through the mitochondrial pathway but did not activate caspase-8 in the cells. In addition, xanthoceraside inhibited the expression of the insulin-like growth factor-1 receptor (IGF-1R), which is an important prosurvival, antiapoptotic signaling growth factor receptor that is frequently overexpressed in cancer cells and used as a therapeutic target for multiple cancers. Interestingly, xanthoceraside also decreased the expression of Raf, p-MEK, and p-ERK, the downstream effectors of IGF-1R. Taken together, these findings indicate that xanthoceraside induces apoptosis through a mitochondria-mediated apoptotic pathway, which is induced by the downregulation of IGF-1R/Raf/MEK/ERK cascades in A375.S2 cells.

The role of the apoptosis-related protein BCL-B in the regulation of mitophagy in hepatic stellate cells during the regression of liver fibrosis

Qian Ding,Xiao-Li Xie,Miao-Miao Wang,Jie Yin,Jin-Mei Tian,Xiao-Yu Jiang,Di Zhang,Jing Han,Yun Bai,Zi-Jin Cui,Hui-Qing Jiang 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

The clearance of activated hepatic stellate cells (HSCs) by apoptosis is critical for the reversibility of hepatic fibrosis. Mitochondrial homeostasis is regulated by mitophagy, which is an efficient way of clearing injured mitochondria that plays an important role in apoptosis. However, the role of mitophagy in apoptosis in HSCs and hepatic fibrosis is still unclear. Here, we show that mitophagy is enhanced in parallel with increased apoptosis in hepatic stellate cells during the reversal of hepatic fibrosis. The inhibition of mitophagy suppressed apoptosis in HSCs and aggravated hepatic fibrosis in mice. In contrast, the activation of mitophagy induced apoptosis in HSCs. Furthermore, we confirmed that BCL-B, which is a member of the BCL-2 family, is a regulator mediating mitophagy-related apoptosis. The knockdown of BCL-B resulted in increased apoptosis and mitophagy in HSCs, while the overexpression of BCL-B caused the opposite effects. BCL-B inhibited the phosphorylation of Parkin (a key regulator of mitophagy) and directly bound phospho-Parkin. Altogether, enhanced mitophagy promotes apoptosis in HSCs during the reversal of hepatic fibrosis. BCL-B suppresses mitophagy in HSCs by binding and suppressing phospho-Parkin, thereby inhibiting apoptosis. BCLB- dependent mitophagy is a new pathway for the regulation of apoptosis in HSCs during the regression of hepatic fibrosis

Autophagy Inhibition Sensitizes Cisplatin Cytotoxicity in Human Gastric Cancer Cell Line Sgc7901

Zhang, Hui-Qing,He, Bo,Fang, Nian,Lu, Shan,Liao, Yu-Qian,Wan, Yi-Ye Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

We aimed to investigate the mechanism and effects of autophagy on cisplatin (DDP)-induced apoptosis in human gastric cancer cell line SGC7901. After SGC7901 cells were treated with DDP and/or chloroquine, cell proliferation was measured using MTT assay; cell apoptosis was determined by flow cytometry; autophagy and apotosis-related proteins expression were detected by Western blot; and quantitative analysis of autophagy after monodansylcadaverine (MDC) staining was performed using fluorescence microscopy. We found after treatment with 5 mg/L DDP for 24 h, the rates of cell apoptosis were ($21.07{\pm}2.12$)%. Autophagy, characterized by an increase in the number of autophagic vesicles and the level of LC3-II protein was observed in cells treated with DDP. After inhibition of autophagy by chloroquine, the rates of cell apoptosis were increased to ($30.16{\pm}3.54$)%, and the level of Caspase-3 and P53 protein were increased, and Bcl-2 protein was decreased. Therefore, autophagy protects human gastric cancer cell line SGC7901 against DDP-induced apoptosis, inhibition of autophagy can promote apoptosis, and combination therapy with DDP and chloroquine may be a promising therapeutic strategy for gastric cancer.