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.

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.

Fixed-Time Disturbance Observer-Based Control for Uncertainty Systems Applied to Permanent-Magnet Speed Control

Wang Da-Zhi,Sun Li-Song,Sun Guo-Feng 대한전기학회 2024 Journal of Electrical Engineering & Technology Vol.19 No.6

For a class of uncertain systems, a fi xed-time disturbance observer is suggested. The proposed observer not only estimated the disturbance but also ensured the fi xed-time convergence, leading to the increased accuracy of the disturbance estimation together with the improved estimation speed. Taking the proposed observer in combination with a state-feedback controller and employing it in a fully actuated system, stabilization of the closed-loop system will be assured which allows the control of uncertain systems. With a numerical example to illustrate the effi cacy of the scheme, fi nally, such scheme is successfully applied to the permanent-magnet speed control system, the results show that it has the advantages of rapid convergence speed and favorable control performance.

Astilbin alleviates sepsis-induced acute lung injury by inhibiting the expression of macrophage inhibitory factor in rats

Hong-bo Zhang,Li-chao Sun,Li-da Zhi,Qian-kuan Wen,Zhi-wei Qi,Sheng-tao Yan,Wen Li,Guo-qiang Zhang 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.10

Sepsis is a systemic inflammatory responsesyndrome caused by severe infections. Astilbin is a dihydroflavonolderivative found in many medicinal and foodplants with multiple pharmacological functions. To investigatethe effects of astilbin on sepsis-induced acute lunginjury (ALI), cecal ligation and puncture was performed onrats to establish a sepsis-induced ALI model; these ratswere then treated with astilbin at different concentrations. Lung injury scores, including lung wet/dry ratio, proteinleakage, myeloperoxidase activity, and inflammatory cellinfiltration were determined to evaluate the effects ofastilbin on sepsis-induced ALI. We found that astilbintreatment significantly attenuates sepsis-induced lunginjury and improves survival rate, lung injury scores, lungwet/dry ratio, protein leakage, myeloperoxidase activity,and inflammatory cell infiltration. Astilbin treatment alsodramatically decreased the production of inflammatorycytokines and chemokines in bronchoalveolar lavage fluid. Further, astilbin treatment inhibited the expression andproduction of macrophage inhibitory factor (MIF), whichinhibits the inflammatory response. Collectively, these datasuggest that astilbin has a protective effect against sepsisinducedALI by inhibiting MIF-mediated inflammatoryresponses. This study provides a molecular basis for astilbinas a new medical treatment for sepsis-induced ALI.

Circular RNA cFAM210A, degradable by HBx, inhibits HCC tumorigenesis by suppressing YBX1 transactivation

Yu Jian,Li Wen,Hou Guo-jun,Sun Da-peng,Yang Yuan,Yuan Sheng-xian,Dai Zhi-hui,Yin Hao-zan,Sun Shu-han,Huang Gang,Zhou Wei-ping,Yang Fu 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Hepatitis B protein x (HBx) has been reported to promote tumorigenesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but the mechanism awaits further investigation. In this study, we found that cFAM210A (a circular RNA derived from the third exon of transcript NM_001098801 of the FAM210A gene; CircBase ID: hsa_circ_0003979) can be silenced by HBx. cFAM210A expression was downregulated and negatively correlated with tumorigenesis in patients with HBV-related HCC. Furthermore, cFAM210A reduced the proliferation, stemness, and tumorigenicity of HCC cells. Mechanistically, HBx increased the N6-methyladenosine (m6A) level of cFAM210A by promoting the expression of RBM15 (an m6A methyltransferase), thus inducing the degradation of cFAM210A via the YTHDF2-HRSP12-RNase P/MRP pathway. cFAM210A bound to YBX1 and inhibited its phosphorylation, suppressing its transactivation function toward MET. These findings suggest the important role of circular RNAs in HBx-induced hepatocarcinogenesis and identify cFAM210A a potential target in the prevention and treatment of HBV-related HCC.

Prognostic Significance of Overexpression of EZH2 and H3k27me3 Proteins in Gastric Cancer

He, Long-Jun,Cai, Mu-Yan,Xu, Guo-Liang,Li, Jian-Jun,Weng, Zi-Jin,Xu, Da-Zhi,Luo, Guang-Yu,Zhu, Sen-Lin,Xie, Dan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

The enhancer of zeste homolog 2 (EZH2) methyl transferase and histone 3 lysine 27 (H3K27me3) protein can repress gene transcription, and their aberrant expression has been observed in various human cancers. This study determined their expression levels in gastric cancer tissues with reference to clinicopathological features and patient survival. We collected 117 gastric cancer and corresponding normal tissues for immunohistochemistry analysis. In gastric cancers, 82/117 (70.1%) were positive for EZH2 and 66/117 (56.4%) for H3K27me3 proteins in contrast to only 5.41% and 7.25% of normal gastric mucosa specimens, respectively. Kaplan-Meier survival data showed the average overall and disease-free survival of EZH2 high expression patients was 25.2 and 20.2 months, respectively, shorter than that with EZH2 low expression (40.5 and 35.9 months). The average overall survival and disease-free survival of high H3K27me3 expression patients was 23.4 and 17.4 months, shorter than without H3K27me3 expression (37.6 and 34.5 months). The average overall survival and disease-free survival of patients with both EZH2 and H3K27me3 expression was 18.8 and 12.9 months, respectively, shorter than that with either alone (34.7 and 31.2 months) or with low levels of both (43.9 and 39.9 months). Multivariate Cox regression analysis showed that H3K27me3 and EZH2 expression, tumor size differentiation and clinical stage were all independent prognostic factors for predicting patient survival. This study demonstrated that detection of both EZH2 and H3K27me3 proteins can predict poor survival of gastric cancer patients, superior to single protein detection. In addition, H3K27me3 and EZH2 protein expression could predict lymph node metastasis.

Study on molten salt oxidation process of simulated Co doped cation exchange resins

Yun Xue,Yue-Lin Wang,Yu Li,Wen-Da Xu,Fu-Qiu Ma,Yang-Hai Zheng,Qing-Guo Zhang,Zhi Zhang,Mi-lin Zhang,Yong-De Yan 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.126 No.-

Cation exchange resins (CERs) are widely applied to purify waste liquids generated during the operationof nuclear reactors. The radioactive nuclides 60Co and 58Co are important corrosion activation products inreactor cooling water. In this study, the simulated Co doped CERs were oxidized with ternary carbonate. According to the thermogravimetric analysis (TG), the decomposition of Co doped CERs includes threeprocesses: 1. Elimination of the osmotic water; 2. Pyrolysis of sulfonic acid group; 3. Destruction of styrene–divinylbenzene copolymer. The X-Ray Diffraction (XRD) patterns indicate that sulfur mainly exists inthe form of sulfate in waste salt. The Co2+ undergoes the path of CoS2 ? Co3O4 with the increase of temperatureand the transition point is 650 C. Combined with Fourier Transform Infrared Spectrometer (FTIR)spectra and X-ray Photoelectron Spectroscopy (XPS) analysis, sulfonic acid groups begin to decomposeat 350 C. During the molten salt oxidation process, most of the sulfur in sulfonic acid groups is entrappedby carbonate as the form of sulfate, and a little of which remains as sulfone group, sulfoxide group andsulfur bridge in residue. When the resins are oxidized at 800 C, the retention rate of Co2+ is 97.3%, indicatingthat the molten salt oxidation can effectively remain Co2+ and convert it into a more stablesubstance.

Lack of Associations of the COMT Val158Met Polymorphism with Risk of Endometrial and Ovarian Cancer: a Pooled Analysis of Case-control Studies

Liu, Jin-Xin,Luo, Rong-Cheng,Li, Rong,Li, Xia,Guo, Yu-Wu,Ding, Da-Peng,Chen, Yi-Zhi Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

This meta-analysis was conducted to examine whether the genotype status of Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with endometrial and ovarian cancer risk. Eligible studies were identified by searching several databases for relevant reports published before January 1, 2014. Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. In total, 15 studies (1,293 cases and 2,647 controls for ovarian cancer and 2,174 cases and 2,699 controls for endometrial cancer) were included in the present meta-analysis. When all studies were pooled into the meta-analysis, there was no evidence for significant association between COMT Val158Met polymorphism and ovarian cancer risk (Val/Met versus Val/Val: OR=0.91, 95% CI=0.76-1.08; Met/Met versus Val/Val: OR=0.90, 95% CI=0.73-1.10; dominant model: OR=0.90, 95% CI=0.77-1.06; recessive model: OR=0.95, 95% CI=0.80-1.13). Similarly, no associations were found in all comparisons for endometrial cancer (Val/Met versus Val/Val: OR 0.97, 95% CI=0.77-1.21; Met/Met versus Val/Val: OR=1.02, 95% CI=0.73-1.42; dominant model: OR=0.98, 95% CI=0.77-1.25; recessive model: OR=1.02, 95% CI=0.87-1.20). In the subgroup analyses by source of control and ethnicity, no significant associations were found in any subgroup of population. This meta-analysis strongly suggests that COMT Val158Met polymorphism is not associated with increased endometrial and ovarian cancer risk.

Comparison of Liver Transplantation and Liver Resection for Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus Type I and Type II

Jia-Yu Lv,Ning-Ning Zhang,Ya-Wei Du,Ying Wu,Tian-Qiang Song,Ya-Min Zhang,Yan Qu,Yu-Xin Liu,Jie Gu,Ze-Yu Wang,Yi-Bo Qiu,Bing Yang,Da-Zhi Tian,Qing-Jun Guo,Li Zhang,Ji-San Sun,Yan Xie,Zheng-Lu Wang,Xin 연세대학교의과대학 2021 Yonsei medical journal Vol.62 No.1

Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellularcarcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involvedand divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were comparedbefore and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR(p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longermedian RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335,respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase(AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion: LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels>200 ng/mL.