Cathepsin D deficiency delays central nervous system myelination by inhibiting proteolipid protein trafficking from late endosome/lysosome to plasma membrane

Da-Zhi Guo,Lin Xiao,Yi-Jun Liu,Chen Shen,Hui-Fang Lou,Yan Lv,Shu-Yi Pan 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

This study aimed to investigate the role of cathepsin D (CathD) in central nervous system (CNS) myelination and its possible mechanism. By using CathD knockout mice in conjunction with immunohistochemistry, immunocytochemistry and western blot assays, the myelination of the CNS and the development of oligodendrocyte lineage cells in vivo and in vitro were observed. Endocytosis assays, real-time-lapse experiments and total internal reflection fluorescence microscopy were used to demonstrate the location and movement of proteolipid protein in oligodendrocyte lineage cells. In addition, the relevant molecular mechanism was explored by immunoprecipitation. The increase in Fluoromyelin Green staining and proteolipid protein expression was not significant in the corpus callosum of CathD−/− mice at the age of P11, P14 and P24. Proteolipid protein expression was weak at each time point and was mostly accumulated around the nucleus. The number of oligodendrocyte lineage cells (olig2+) and mature oligodendrocytes (CC1+) significantly decreased between P14 and P24. In the oligodendrocyte precursor cell culture of CathD−/− mice, the morphology of myelin basic protein-positive mature oligodendrocytes was simple while oligodendrocyte precursor cells showed delayed differentiation into mature oligodendrocytes. Moreover, more proteolipid protein gathered in late endosomes/lysosomes (LEs/Ls) and fewer reached the plasma membrane. Immunohistochemistry and immunoelectron microscopy analysis showed that CathD, proteolipid protein and VAMP7 could bind with each other, whereas VAMP7 and proteolipid protein colocalized with CathD in late endosome/lysosome. The findings of this paper suggest that CathD may have an important role in the myelination of CNS, presumably by altering the trafficking of proteolipid protein.

Running spectral index and mode-mode correlation of inflationary perturbations from off-equilibrium effects

Da-Shin Lee,Li-Zhi Fang,Wolung Lee,Yeo-Yie Charng 한국물리학회 2004 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.45 No.1

We study the off-equilibrium effects of the in aton field on the dynamics of primordial perturbations in the O(N) model. A self-consistent off-equilibrium formalism is employed to investigate the evolution of the in ationary background eld and its uctuations with the back-reaction effects. We nd two observable remains left behind after the off-equilibrium processes: the running spectral index of primordial density perturbations and the correlations between perturbation modes in phase space, which can serve as the imprints to probe the epoch of in ation, and beyond.

A Novel 7-O-Modified Genistein Derivative with Acetylcholinesterase Inhibitory Effect, Estrogenic Activity and Neuroprotective Effect

Da-Hua Shi,Jun-Hua Wu,Zhi-Qiang Yan,Li-Na Zhang,Yu-Rong Wang,Chun-Ping Jiang 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.9

To find the multi-target-directed compounds for the treatment of Alzheimer’s disease (AD), we synthesized 7-(4-(diethylamino)butoxy)-5-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one, a novel 7-O-modified genistein derivative (GS-14), and investigated its acetylcholinesterase (AChE) inhibitory effect, estrogenic activity and neuroprotective effect. GS-14 acted as a selective AChE inhibitor in vitro, with an IC50 value of 0.17 μM and showed no inhibition activity against butyrylcholinesterase (BuChE). The Lineweaver–Burk plot revealed that GS-14 was a non-competitive AChE inhibitor with a Ki value of 0.23 μM and the molecular docking model indicated that GS-14 interacted with the peripheral anionic site (PAS) of AChE. The MCF-7 proliferation assay demonstrated that GS-14 possessed estrogenic activity and GS-14 exhibited a high specificity for estrogen receptor β (ERβ) with a dissociation constant (Ki) of 2.86 nM compared with that of 1.01 μM for estrogen receptor α (ERα) in the molecular docking study. GS-14 also possessed a neuroprotective effect and showed the best protective effect against the β-amyloid protein-induced injury on SH-SY5Y cells at a concentration of 1 nM. Considering its AChEinhibition activity, estrogenic activity and neuroprotective effect, GS-14 may be a potential multi-target agent for the treatment of AD.

Vibration analysis of viscoelastic single-walled carbon nanotubes resting on a viscoelastic foundation

Da-Peng Zhang,Yong-Jun Lei,Cheng-Yuan Wang,Zhi-Bin Shen 대한기계학회 2017 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.31 No.1

Vibration responses were investigated for a viscoelastic Single-walled carbon nanotube (visco-SWCNT) resting on a viscoelastic foundation. Based on the nonlocal Euler-Bernoulli beam model, velocity-dependent external damping and Kelvin viscoelastic foundation model, the governing equations were derived. The Transfer function method (TFM) was then used to compute the natural frequencies for general boundary conditions and foundations. In particular, the exact analytical expressions of both complex natural frequencies and critical viscoelastic parameters were obtained for the Kelvin-Voigt visco-SWCNTs with full foundations and certain boundary conditions, and several physically intuitive special cases were discussed. Substantial nonlocal effects, the influence of geometric and physical parameters of the SWCNT and the viscoelastic foundation were observed for the natural frequencies of the supported SWCNTs. The study demonstrates the efficiency and robustness of the developed model for the vibration of the visco-SWCNT-viscoelastic foundation coupling system.

Revision of the spider genus Taira (Araneae, Amaurobiidae, Amaurobiinae)

Zhi-Sheng Zhang,Ming-Sheng Zhu,Da-Xiang Song 한국거미연구소 2008 한국거미 Vol.24 No.2

The cribellate amaurobiid genus Taira, which is suggested to be most similar to the genus Amaurobius and someother related genera, is revised based on genital characters. Eight species, one from Japan and seven from China, areincluded. Five new species from China are described: T. cangshan, T. concava, T. latilabiata, T. obtusa, and T. sulciformis.Titanoeca decorata Yin & Bao 2001 is newly transferred to this genus and its male is described for the first time. Tairalunaris Wang & Ran 2004 is newly synonymized with T. liboensis Zhu, Chen & Zhang 2004.

Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression

Da Zhou,Yuan-Wen Chen,Ze-Hua Zhao,Rui-Xu Yang,Feng-Zhi Xin,Xiao-Lin Liu,Qin Pan,Huiping Zhou,Jian-Gao Fan 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is wellknown that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/ insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

Hypoxia Induced Multidrug Resistance of Laryngeal Cancer Cells via Hypoxia-inducible Factor-1α

Li, Da-Wei,Dong, Pin,Wang, Fei,Chen, Xin-Wei,Xu, Cheng-Zhi,Zhou, Liang Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

Objectives: To investigate whether hypoxia has an effect on regulation of multidrug resistance (MDR) to chemotherapeutic drugs in laryngeal carcinoma cells and explore the role of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$). Methods: Laryngeal cancer cells were cultured under normoxic and hypoxic conditions. The sensitivity of the cells to multiple drugs and levels of apoptosis induced by paclitaxel were determined by MTT assay and annexin-V/propidium iodide staining analysis, respectively. HIF-$1{\alpha}$ expression was blocked by RNA interference. The expression of HIF-$1{\alpha}$ gene was detected by real-time quantitative RT-PCR and Western blotting. The value of fluorescence intensity of intracellular adriamycin accumulation and retention in cells was evaluated by flow cytometry. Results: The sensitivity to multiple chemotherapy agents and induction of apoptosis by paclitaxel could be reduced by hypoxia (P<0.05). A the same time, the adriamycin releasing index of cells was increased (P<0.05). However, resistance acquisition subject to hypoxia in vitro was suppressed by down-regulating HIF-$1{\alpha}$ expression. Conclusion: HIF-$1{\alpha}$ could be considered as a key regulator for mediating hypoxia-induced MDR in laryngeal cancer cells via inhibition of drug-induced apoptosis and decrease in intracellular drug accumulation.

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.

Breastfeeding and Ovarian Cancer Risk: a Systematic Review and Meta-analysis of 40 Epidemiological Studies

Li, Da-Peng,Du, Chen,Zhang, Zuo-Ming,Li, Guang-Xiao,Yu, Zhi-Fu,Wang, Xin,Li, Peng-Fei,Cheng, Cheng,Liu, Yu-Peng,Zhao, Ya-Shuang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

The present systematic review and meta-analysis was conducted to assess any association between breastfeeding and the risk of ovarian cancer. A systematic search of published studies was performed in PUBMED and EMBASE and by reviewing reference lists from retrieved articles through March 2013. Data extraction was conducted independently by two authors. Pooled relative risk ratios were calculated using random-effect models. Totals of 5 cohort studies and 35 case-control studies including 17,139 women with ovarian cancer showed a 30% reduced risk of ovarian cancer when comparing the women who had breastfed with those who had never breastfed (pooled RR = 0.70, 95% CI: 0.64-0.76; p = 0.00), with significant heterogeneity in the studies (p = 0.00; I2 = 76.29%). A significant decreasd in risk of epithelial ovarian cancer was also observed (pooled RR = 0.68, 95% CI: 0.61-0.76). When the participants were restricted to only parous women, there was a slightly attenuated but still significant risk reduction of ovarian cancer (pooled RR = 0.76, 95% CI: 0.69-0.83). For total breastfeeding duration, the pooled RRs in the < 6 months, 6-12 months and > 12 months of breastfeeding subgroups were 0.85 (95% CI: 0.77-0.93), 0.73 (95% CI: 0.65-0.82) and 0.64 (95%CI: 0.56-0.73), respectively. Meta-regression of total breastfeeding duration indicated an increasing linear trend of risk reduction of ovarian cancer with the increasing total breastfeeding duration (p = 0.00). Breastfeeding was inversely associated with the risk of ovarian cancer, especially long-term breastfeeding duration that demonstrated a stronger protective effect.

A Prognostic Model To Predict Survival In Stage III Colon Cancer Patients Based on Histological Grade, Preoperative Carcinoembryonic Antigen Level and the Neutrophil Lymphocyte Ratio

Wuxiao, Zhi-Jun,Zhou, Hai-Yan,Wang, Ke-Feng,Chen, Xiao-Qin,Hao, Xin-Bao,Lu, Yan-Da,Xia, Zhong-Jun Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.2

Background: Stage III colon cancer patients demonstrate diverse clinical outcomes. The aim of this study was to develop a prognostic model in order to better predict their survival. Materials and Methods: From 2004 to 2010, 548 patients were retrospectively analyzed, among whom 328 were defined as the study group and the remaining 220 served as a validation group. Clinico-pathologic features, including age, gender, histological grade, T stage, number of positive lymph nodes, number of harvest lymph nodes, pretreatment carcinoembryonic antigen (CEA) levels and pretreatment neutrophil lymphocyte ratio (NLR), were collected. Kaplan-Meier survival curves were used to detect prognostic factors and multivariate analysis was applied to identify independent examples on which to develop a prognostic model. Finally, the model was further validated with the validation group. Results: Histological grade (p=0.002), T stage (p=0.011), number of positive lymph nodes (p=0.003), number of harvested lymph nodes (p=0.020), CEA (p=0.005), and NLR (p<0.001) were found as prognostic factors while histological grade [RR(relative risk):0.632, 95%CI (Confidence interval) 0.405~0.985, p=0.043], CEA (RR:0.644, 95%CI:0.431~0.964, p=0.033) and NLR (RR:0.384, 95%CI:0.255~0.580, p<0.001) levels were independent. The prognostic model based on these three factors was able to classify patients into high risk, intermediate and low risk groups (p<0.001), both in study and validation groups. Conclusions: Histological grade, pretreatment CEA and NLR levels are independent prognostic factors in stage III colon cancer patients. A prognostic model based on these factors merits attention in future clinical practice.