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.

Spectroscopic Determination of the Species Fractions and the Power Profiles of the Diagnostic Neutral Beam on the HT-7 Tokamak

Jia Fu,Yuejiang Shi,Yingying Li,Fudi Wang,Sheng Liu,Jian Zhang,Jun Li,Yiyyun Huang,Yuanlai Xie,Zhimin Liu,Chundong Hu,Chundong Hu,DNB Team,William Rowan,He Huang 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.58 No.5

A diagnostic neutral beam (DNB) has been installed on the HT-7 tokamak for the measurement of charge exchange recombination spectroscopy (CXRS). The H_α-light Doppler shift spectroscopy from the drifted duct is measured to determine the components of the neutral beam. The fractions of neutral beam species are investigated under a wide range of arc voltages and extraction high voltages of the beam aimed to the optimized species fractions for the CXRS applications. A magnet ring is used to improve the magnetic property of the ion source. The result shows that the full-energy component fractions increase from 19 to 25 percent with optimization of the beam operation, but with a dramatic increase of the water component. There are nine optical fiber channels observing one section of the beam simultaneously for this spectroscopy, which provides information of the power profiles of the beam. The full width at half maximum (FWHM) of the beam profile is 8 cm, as measured by using the spectroscopy.

Identification of a Cancer Stem-like Population in the Lewis Lung Cancer Cell Line

Zhang, An-Mei,Fan, Ye,Yao, Quan,Ma, Hu,Lin, Sheng,Zhu, Cong-Hui,Wang, Xin-Xin,Liu, Jia,Zhu, Bo,Sun, Jian-Guo,Chen, Zheng-Tang Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3

Objective: Although various human cancer stem cells (CSCs) have been defined, their applications are restricted to immunocompromised models. Developing a novel CSC model which could be used in immunocompetent or transgenic mice is essential for further understanding of the biomolecular characteristics of tumor stem cells. Therefore, in this study, we analyzed murine lung cancer cells for the presence of CSCs. Methods: Side population (SP) cells were isolated by fluorescence activated cell sorting, followed by serum-free medium (SFM) culture, using Lewis lung carcinoma cell (LLC) line. The self-renewal, differentiated progeny, chemosensitivity, and tumorigenic properties in SP and non-SP cells were investigated through in vitro culture and in vivo serial transplantation. Differential expression profiles of stem cell markers were examined by RT-PCR. Results: The SP cell fraction comprised 1.1% of the total LLC population. SP cells were available to grow in SFM, and had significantly enhanced capacity for cell proliferation and colony formation. They were also more resistant to cisplatin in comparison to non-SP cells, and displayed increased tumorigenic ability. Moreover, SP cells showed higher mRNA expression of Oct-4, ABCG2, and CD44. Conclusion: We identified SP cells from a murine lung carcinoma, which possess well-known characteristics of CSCs. Our study established a useful model that should allow investigation of the biological features and pharmacosensitivity of lung CSCs, both in vitro and in syngeneic immunocompetent or transgenic/knockout mice.

Current Evidence on the Relationship Between Two Polymorphisms in the NBS1 Gene and Breast Cancer Risk: a Meta-analysis

Zhang, Zhi-Hua,Yang, Lin-Sheng,Huang, Fen,Hao, Jia-Hu,Su, Pu-Yu,Sun, Ye-Huan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

Introduction: Published studies on the association between Nijmegen breakage syndrome 1(NBS1) gene polymorphisms and breast cancer risk have been inconclusive, and a meta-analysis was therefore performed for clarification. Methods: Eligible articles were identified by a search of MEDLINE and EMBASE bibliographic databases for the period up to March 2012. The presence of between-study heterogeneity was investigated using the chi-square-based Cochran's Q statistic test. When there was statistical heterogeneity, the random effects model was chosen; otherwise, fixed effects estimates were reported as an alternative approach. Results: A total of 11 eligible articles (14 case-control studies) were identified, nine case-control studies were for the 657del5 mutation (7,534 breast cancer cases, 14,034 controls) and five case-control studies were for the I171V mutation (3,273 breast cancer cases, 4,004 controls). Our analysis results indicated that the 657del5 mutation was associated with breast cancer risk (carriers vs. non-carriers: pooled OR =2.63, 95% CI: 1.76-3.93), whereas the I171V mutation was not (carriers vs. non-carriers: pooled OR =1.52, 95% CI: 0.70-3.28). Conclusion: The present meta-analysis suggests that the 657del5 gene mutation in the NBS1 gene plays a role in breast cancer risk, while the I171V mutation does not exert a significant influence.

Risk of Treatment-related Mortality with Sorafenib in Patients with Cancer

Zhang, Xin-Ji,Zhang, Tian-Yi,Yu, Fei-Fei,Wei, Xin,Li, Ye-Sheng,Xu, Feng,Wei, Li-Xin,He, Jia Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Background: Fatal adverse events (FAEs) have been reported with sorafenib, a vascular endothelial growth factor receptor kinase inhibitor (VEGFR TKI). We here performed an up-to-date and detailed meta-analysis to determine the overall risk of FAEs associated with sorafenib. Methods: Databases, including PubMed, Embase and Web of Science, and abstracts presented at the American Society of Clinical Oncology annual meetings were searched to identify relevant studies. Eligible studies included randomized controlled trials evaluating sorafenib effects in patients with all malignancies. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated for FAEs. In addition, subgroup analyses were performed according to tumor type and therapy regimen. Results: 13 trials recruiting 5,546 patients were included in our analysis. The overall incidence of FAEs with sorafenib was 1.99% (95%CI, 0.98-4.02%). Patients treated with sorafenib had a significantly increased risk of FAEs compared with patients treated with control medication, with an RR of 1.77 (95%CI 1.25-2.52, P=0.001). Risk varied with tumour type, but appeared independent of therapy regimen. A significantly increased risk of FAEs was observed in patients with lung cancer (RR 2.26; 95% CI 1.03-4.99; P= 0.043) and renal cancer (RR 1.84; 95% CI 1.15-2.94; P= 0.011). The most common causes of FAEs were hemorrhage (8.6%) and thrombus or embolism (4.9%). Conclusions: It is important for health care practitioners to be aware of the risks of FAEs associated with sorafenib, especially in patients with renal and lung cancer.

Association of CYP2E1 and NAT2 Polymorphisms with Lung Cancer Susceptibility among Mongolian and Han Populations in the Inner Mongolian Region

Zhang, Jing-Wen,Yu, Wan-Jia,Sheng, Xiao-Min,Chang, Fu-Hou,Bai, Tu-Ya,Lv, Xiao-Li,Wang, Guang,Liu, Su-Zhen Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21

Purpose: To explore associations of CYP2E1 and NAT2 polymorphisms with lung cancer susceptibility among Mongolian and Han populations in the Inner Mongolian region. Materials and Methods: CYP2E1 and NAT2 polymorphisms were detected by PCR-RFLP in 930 lung cancer patients and 1000 controls. Results: (1) Disequilibrium of the distribution of NAT2 polymorphism was found in lung cancer patients among Han and Mongolian populations (p=0.031). (2) Lung cancer risk was higher in individuals with c1, D allele of CYP2E1 RsaI/PstI, DraI polymorphisms and slow acetylation of NAT2 (c1 compared with c2, OR=1.382, 95%CI: 1.178-1.587, p=0.003; D compared with C, OR=1.241, 95%CI: 1.053-1.419, P<0.001; slow acetylation compared with rapid acetylation, OR=1.359, 95%CI:1.042-1.768, p=0.056) (3) Compared with c2/c2 and rapid acetylation, c1/c1 together with slow acetylation synergetically increased risk of lung cancer 2.83 fold. (4) Smokers with CYP2E1 c1/c1, DD, and NAT2 slow acetylation have 2.365, 1.916, 1.841 fold lung cancer risk than others with c2/c2, CC and NAT2 rapid acetylation, respectively. (5) Han smokers with NAT2 slow acetylation have 1.974 fold lung cancer risk than others with rapid acetylation. Conclusions: Disequilibrium distribution of NAT2 polymorphism was found in lung cancer patients among Han and Mongolian populations. Besides, Han smokers with NAT2 slow acetylation may have higher lung cancer risk compared with rapid acetylation couterparts. CYP2E1 c1/c1, DD and NAT2 slow acetylation, especially combined with smoking, contributes to the development of lung cancer. CYP2E1 c1/c1 or DD genotype and NAT2 slow acetylation have strong synergistic action in increasing lung cancer risk.

Soluble Expression of Recombinant Human Smp30 for Detecting Serum Smp30 Antibody Levels in Hepatocellular Carcinoma Patients

Zhang, Sheng-Chang,Huang, Peng,Zhao, Yong-Xiang,Liu, Shu-Yan,He, Shu-Jia,Xie, Xiao-Xun,Luo, Gou-Rong,Zhou, Su-Fang Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Senescence marker protein 30 (SMP30), a hepatocellular carcinoma (HCC) associated antigen, was earlier shown by our research group to be highly expressed in HCC paracancerous tissues, but have low levels in HCC tissues. In order to detect anti-SMP30 antibody in serum of HCC patients, we established pET30a-SMP30 and pColdIII-SMP30 expression systems in Escherichia coli. However, the expression product was mainly in the form of inclusion bodies. In this research, we used several combinations of chaperones, four molecular chaperone plasmids with pET30a-SMP30 and five molecular chaperone plasmids with pColdIII-SMP30 to increase the amount of soluble protein. Results showed that co-expression of HIS-SMP30 with pTf16, combined with the addition of osmosis-regulator, and a two-step expression resulted in the highest enhancement of solubility. A total of 175 cases of HCC serum were studied by ELISA to detect anti-SMP30 antibody with recombinant SMP30 protein. Some 22 were positive and x2 two-sided tests all showed P>0.05, although it remained unclear whether there was a relationship between positive cases and clinical diagnostic data.

Siderophore Production by Rhizosphere Biological Control Bacteria Brevibacillus brevis GZDF3 of Pinellia ternata and Its Antifungal Effects on Candida albicans

Miaomiao Sheng,Huake Jia,Gongyou Zhang,Lina Zeng,Tingting Zhang,Yaohang Long,Jing Lan,Zuquan Hu,Zhu Zeng,Bing Wang,Hongmei Liu 한국미생물·생명공학회 2020 Journal of microbiology and biotechnology Vol.30 No.5

Brevibacillus brevis GZDF3 is a gram-positive, plant growth-promoting rhizosphere bacterium (PGPR) isolated from the rhizosphere soil of Pinellia ternata (an important herb in traditional Chinese medicine). The GZDF3 strain produces certain active compounds, such as siderophores, which are the final metabolite products of non-ribosomal peptide synthetase (NRPS) and independent non-ribosomal peptide synthetase (NIS) activity. With the present study, we attempted to investigate the siderophore production characteristics and conditions of Bacillus sp. GZDF3. The antibacterial activity of the siderophores on pathogenic fungi was also investigated. Optimal conditions for the synthesis of siderophores were determined by single factor method, using sucrose 15 g/l, asparagine 2 g/l, 32°C, and 48 h. The optimized sucrose asparagine medium significantly increased the production of siderophores, from 27.09% to 54.99%. Moreover, the effects of different kinds of metal ions on siderophore production were explored here. We found that Fe3+ and Cu2+ significantly inhibited the synthesis of siderophores. The preliminary separation and purification of siderophores by immobilized-metal affinity chromatography (IMAC) provides strong antibacterial activity against Candida albicans. The synergistic effect of siderophores and amphotericin B was also demonstrated. Our results have shown that the GZDF3 strain could produce a large amount of siderophores with strong antagonistic activity, which is helpful in the development of new biological control agents.

Detection for Tobacco Mosaic Virus and Potato Virus Y by DNA Chips Techniques

Hui Jia,Jin-Zhong Wang,Si-yuan Wen,Sheng-Qi Wang,Jin-Gao Dong,Min-Zhao Zhang 한국원예학회 2006 한국원예학회 기타간행물 Vol.- No.-

Analysis and Design of a New Topology of Soft-Switching Inverters

Rong Chen,Jia-Sheng Zhang 전력전자학회 2013 JOURNAL OF POWER ELECTRONICS Vol.13 No.1

This paper proposes the power conversion mechanism of a bailer-charge-transfer zero-current-switching (CT-ZCS) circuit. The operation modes are analyzed and researched using state trajectory equations. The topology of CT-ZCS based on soft-switching inverters offers some merits such as: tracking the input reference signal dynamically, bearing load shock and short circuit, multiplying inverter N+1 redundancy parallel, coordinating power balance for easy control, and soft-switching commutation for high efficiency and large capacity. These advantages are distinctive from conventional inverter topologies and are especially demanded in AC drives: new energy generation and grid, distributed generation systems, switching power amplifier, active power filter, and reactive power compensation and so on. Prototype is manufactured and experiment results show the feasibility and dynamic voltage-tracking characteristics of the topology.