Phosphorylation of DYNLT1 at Serine 82 Regulates Microtubule Stability and Mitochondrial Permeabilization in Hypoxia

Xue Xu,Yue-sheng Huang,Qiong Zhang,Jiong-yu Hu,Dong-xia Zhang2,Xu-pin Jiang,jie-zhi Jia,Jing-ci Zhu 한국분자세포생물학회 2013 Molecules and cells Vol.36 No.4

Hypoxia-induced microtubule disruption and mitochondrial permeability transition (mPT) are crucial events leading to fatal cell damage and recent studies showed that microtubules (MTs) are involved in the modulation of mitochondrial function. Dynein light chain Tctex-type 1 (DYNLT1) is thought to be associated with MTs and mitochondria. Previously we demonstrated that DYNLT1 knockdown aggravates hypoxia-induced mitochondrial permeabilization, which indicates a role of DYNLT1 in hypoxic cytoprotection. But the underlying regulatory mechanism of DYNLT1 remains illusive. Here we aimed to investigate the phosphorylation alteration of DYNLT1 at serine 82 (S82) in hypoxia (1% O2). We therefore constructed recombinant adenoviruses to generate S82E and S82A mutants, used to transfect H9c2 and HeLa cell lines. Development of hypoxia-induced mPT (MMP examining, Cyt c release and mPT pore opening assay), hypoxic energy metabolism (cellular viability and ATP quantification), and stability of MTs were examined. Our results showed that phosph-S82 (S82-P) expression was increased in early hypoxia; S82E mutation (phosphomimic) aggravated mitochondrial damage, ele-vated the free tubulin in cytoplasm and decreased the cellular viability; S82A mutation (dephosphomimic) seemed to diminish the hypoxia-induced injury. These data suggest that DYNLT1 phosphorylation at S82 is involved in MTs and mitochondria regulation, and their interaction and cooperation contribute to the cellular hypoxic tolerance. Thus, we provide new insights into a DYNLT1 mechanism in stabilizing MTs and mitochondria, and propose a potential therapeutic target for hypoxia cytoprotective studies.

Overexpression of NDRG2 Can Inhibit Neuroblastoma Cell Proliferation through Negative Regulation by CYR61

Zhang, Zhi-Guo,Li, Gang,Feng, Da-Yun,Zhang, Jian,Zhang, Jing,Qin, Huai-Zhou,Ma, Lian-Ting,Gao, Guo-Dong,Wu, Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Several recent studies have showed that the n-myc downstream regulated gene 2 (NDRG2) is a new tumor suppressor gene, and that it plays an important role in tumor suppression in several cancers or cancer cell lines. However, few studies focused on its function in neuroblastoma cells. In the present investigation, we demonstrated that NDRG2 overexpression inhibited their proliferation. Using a cDNA microarray, we found that overexpression of NDRG2 inhibited the expression of cysteine-rich protein 61 (CYR61), a proliferation related gene. From our research, CYR61 may partially hinder NDRG2-mediated inhibition of cell proliferation. Overexpression of NDRG2 resulted in accumulation of cells in the G1 phase, which was accompanied by upregulation of p21 and p27 and downregulation of CDK4 and cyclin D1. Taken together, these data indicate that NDRG2 inhibits the proliferation of neuroblastoma cells partially through suppression of CYR61. Our findings offer novel insights into the physiological roles of NDRG2 in neuroblastoma cell proliferation, and NDRG2 may prove to be effective candidate for the treatment of children with neuroblastoma.

Patients with Spontaneously Ruptured Hepatocellular Carcinoma Benefit from Staged Surgical Resection after Successful Transarterial Embolization

Zhang, Dong-Zhi,Zhang, Ke,Wang, Xiao-Peng,Cai, Hui Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.1

Background: Surgical resection of spontaneously ruptured hepatocellular carcinoma (HCC) after successful transarterial embolization (TAE) remains controversial. The aim of this study was to investigate its efficacy in a series of cases. Materials and Methods: We retrospectively examined ruptured HCC cases from Jan 2000 to Dec 2008; all of these 126 cases received TAE as the initial therapy. Subsequently, 74 cases received staged surgical resection, and the remaining 52 cases underwent repeated TACE. The baseline demographic data, tumor characteristics, and long term survival were recorded and compared. Results: The demographic and baseline characteristics were comparable between the hepatic resection and TACE groups; furthermore, no significant difference in the tumor characteristics was detected between the two groups. The differences in in-hospital, 30-day and 90-day mortality between the two groups were not significant (P>0.05). However, the 1-, 3-, and 5-year overall survival rates were 85.1%, 63.5%, and 37.8%, respectively, in the hepatic resection group, which were significantly higher than those in the TACE group (69.2%, 46.2%, and 17.3%, respectively, P=0.004). Univariate and multivariate analyses indicated that these patients benefitted from hepatic resection compared with TACE with respect to long-term outcomes. Conclusions: Staged hepatic resection after TAE is an effective treatment that results in superior long-term survival to repeated TACE.

Permanent Magnetic Films

Zhi-dong Zhang 한국자기학회 2010 한국자기학회 학술연구발표회 논문개요집 Vol.2010 No.12

Preparation and Adsorption Properties of PA6/PSMA-OA Molecularly Imprinted Composite Membranes in Supercritical CO₂

Zhang, Qing,Zhang, Xingyuan,Zhang, Wencheng,Pan, Jian,Liu, Ling,Zhang, Haitao,Zhao, Dong,Li, Zhi Korean Chemical Society 2011 Bulletin of the Korean Chemical Society Vol.32 No.9

Oleanolic acid (OA) as template molecule, polyamide-6 (PA6) as basement membrane and poly(styrene-comaleic acid) (PSMA) were used to prepare PA6/PSMA-OA molecularly imprinted composite membranes by phase inversion method in supercritical $CO_2$ ($ScCO_2$). The template molecule (OA), [poly(styrene-co-maleic anhydride) (PSMAH), PSMA, molecularly imprinted membranes (MIMs) imprinting OA and MIMs after elution were all characterized by Fourier transform infrared spectroscopy (FTIR). The conditions that were the mass ratio between PSMA and OA from 3:1 to 8:1, temperature of $ScCO_2$ from $35^{\circ}C$ to $50^{\circ}C$ and pressure of $ScCO_2$ 12 MPa to 17 MPa were studied. It was obtained the largest adsorption rate and purity of OA after adsorption of the resultant MIMs, 50.41% and 96.15% respectively. After using PA6 film and non-woven fabrics as basement membrane respectively, it was found that smaller aperture of PA6 was used as basement membrane, a higher adsorption rate and a higher purity of OA after adsorption of the MIMs were obtained, and so were the stability and reproducibility of the resultant MIMs. After template molecules being removed, the MIMs had effective selectivity hydrogen bonding to separately bind in the binary components to the template molecules-oleanolic acid.

Antitumor Activity of Histone Deacetylase Inhibitor Trichostatin A in Osteosarcoma Cells

Cheng, Dong-Dong,Yang, Qing-Cheng,Zhang, Zhi-Chang,Yang, Cui-Xia,Liu, Yi-Wen Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Background: Histone deacetylase (HDAC) inhibitors have been reported to induce cell growth arrest, apoptosis and differentiation of tumor cells. The present study aimed to examine the effects of trichostatin A (TSA), one such inhibitor, on the cell cycle, apoptosis and invasiveness of osteosarcoma cells. Methods: MG-63 cells were treated with TSA at various concentrations. Then, cell growth and apoptosis were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) and TUNEL assays, respectively; cell cycling was assessed by flow cytometry; invasion assays were performed with the transwell Boyden Chamber system. Results: MTT assays revealed that TSA significantly inhibited the growth of MG-63 cells in a concentration and time dependent manner. TSA treated cells demonstrated morphological changes indicative of apoptosis and TUNEL assays revealed increased apoptosis of MG-63 cells after TSA treatment. Flow cytometry showed that TSA arrested the cell cycle in G1/G2 phase and annexin V positive apoptotic cells increased markedly. In addition, the invasiveness of MG-63 cells was inhibited by TSA in a concentration dependent manner. Conclusion: Our findings demonstrate that TSA inhibits the proliferation, induces apoptosis and inhibits invasiveness of osteosarcoma cells in vitro. HDAC inhibitors may thus have promise to become new therapeutic agents against osteosarcoma.

Preparation and Adsorption Properties of PA6/PSMA-OA Molecularly Imprinted Composite Membranes in Supercritical CO_2

Qing Zhang,Wencheng Zhang,Jian Pan,Ling Liu,Haitao Zhang,Dong Zhao,Zhi Li,Xingyuan Zhang 대한화학회 2011 Bulletin of the Korean Chemical Society Vol.32 No.9

Oleanolic acid (OA) as template molecule, polyamide-6 (PA6) as basement membrane and poly(styrene-comaleic acid) (PSMA) were used to prepare PA6/PSMA-OA molecularly imprinted composite membranes by phase inversion method in supercritical CO_2 (ScCO_2). The template molecule (OA), [poly(styrene-co-maleic anhydride) (PSMAH), PSMA, molecularly imprinted membranes (MIMs) imprinting OA and MIMs after elution were all characterized by Fourier transform infrared spectroscopy (FTIR). The conditions that were the mass ratio between PSMA and OA from 3:1 to 8:1, temperature of ScCO_2 from 35 ºC to 50 ºC and pressure of ScCO_2 12 MPa to 17 MPa were studied. It was obtained the largest adsorption rate and purity of OA after adsorption of the resultant MIMs, 50.41% and 96.15% respectively. After using PA6 film and non-woven fabrics as basement membrane respectively, it was found that smaller aperture of PA6 was used as basement membrane, a higher adsorption rate and a higher purity of OA after adsorption of the MIMs were obtained, and so were the stability and reproducibility of the resultant MIMs. After template molecules being removed, the MIMs had effective selectivity hydrogen bonding to separately bind in the binary components to the template molecules-oleanolic acid.

Effectiveness and Safety of Dabrafenib in the Treatment of 20 Chinese Children with BRAFV600E-Mutated Langerhans Cell Histiocytosis

Ying Yang,Dong Wang,Lei Cui,Hong-Hao Ma,Li Zhang,Hong-Yun Lian,Qing Zhang,Xiao-Xi Zhao,Li-Ping Zhang,Yun-Ze Zhao,Na Li,Tian-You Wang,Zhi-Gang Li,Rui Zhang 대한암학회 2021 Cancer Research and Treatment Vol.53 No.1

Purpose We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH). Materials and Methods A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib. Results The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO– group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients. Conclusion Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.

Fall Detection Algorithm for the Elderly Based on Human Characteristic Matrix and SVM

WANG Rui-dong,ZHANG Yong-liang,DONG Ling-ping,LU Jia-wei,ZHANG Zhi-qin,HE Xia 제어로봇시스템학회 2015 제어로봇시스템학회 국제학술대회 논문집 Vol.2015 No.10

Fall is one of the leading causes of injury and death for the elderly. Real-time fall detection is of great significance for the safety of the elderly. This paper proposes a coarse to fine fall detection algorithm based on Human characteristic matrix and Support Vector Machine (SVM). First, background subtraction and morphological processing are used to obtain more accurately human silhouette. Then, two human characteristic matrices are constructed based on Hu-moment invariant and the information of human body posture extracted from human silhouette and are used as features to train SVM classifier for fall detection. Experimental results indicate that the proposed algorithm can distinguish fall event from other movements such as squat, sitting down and back turning. Compared with other common methods, the proposed method can real-time and efficiently track the video with 18 frames per second.

Reduction of the contact resistance in copper phthalocyanine thin film transistor with UV/ozone treated Au electrodes

Jun Li,Liang Zhang,Xiao-Wen Zhang,Hao Zhang,Xue-Yin Jiang,Dong-bin Yu,Wen-Qing Zhu,Zhi-Lin Zhang 한국물리학회 2010 Current Applied Physics Vol.10 No.5

Bottom-contact (BC) copper phthalocyanine (CuPc) thin film transistor with UV/ozone treated Au as a source/drain electrode was fabricated and the contact resistance was estimated from the transmission line method (TLM). Comparing the properties of OTFT with untreated Au electrode, the performance of the BC CuPc-TFT with the UV/ozone treated Au electrodes was significantly improved: saturation mobility increased from 4.69 × 10−3 to 2.37 × 10−2 ㎠/V s, threshold voltage reduced from −29.1 to −6.4 V, and threshold swing varied from 5.08 to 2.25 V/decade. The contact resistance of the device with UV/ozone treated Au electrodes was nearly 20 times smaller than that of the device with untreated Au electrodes at the gate voltage of −20 V. This result indicated that using the UV/ozone treated Au electrode is an effective method to reduce the contact resistance. The present BC configuration with UV/ozone treated Au electrodes could be a significant step towards the commercialization of OTFT technology.