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.

Characteristics of Diprophylline-Induced Bidirectional Modulation on Rat Jejunal Contractility

Liu, Fang-Fei,Chen, Da-Peng,Xiong, Yong-Jian,Lv, Bo-Chao,Lin, Yuan The Korean Society of Pharmacology 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.1

In this study, we propose that diprophylline exerts bidirectional modulation (BM) on the isolated rat jejunal segment depending on its contractile state. The results supported the hypothesis. Diprophylline ($20{\mu}M$) exerted stimulatory effects on the contractility of jejunal segment in six low contractile states while inhibitory effects in six high contractile states, showing the characteristics of BM. Diprophylline-induced stimulatory effect was significantly blocked by atropine, indicating the correlation with cholinergic activation. Diprophylline-induced inhibitory effect was partially blocked by phentolamine, propranolol, and L-N-Nitro-Arginine respectively, indicating their correlation with sympathetic activation and nitric oxide-mediated relaxing mechanisms. Diprophylline-induced BM was abolished by tetrodotoxin or in a $Ca^{2+}$ free condition or pretreated with tyrosine kinase inhibitor imatinib, suggesting that diprophylline-induced BM is $Ca^{2+}$ dependent, and that it requires the presence of enteric nervous system as well as pacemaker activity of interstitial cells of Cajal. Diprophylline significantly increased the reduced MLCK expression and myosin extent in constipation-prominent rats and significantly decreased the increased MLCK expression and myosin extent in diarrhea-prominent rats, suggesting that the change of MLCK expression may also be involved in diprophylline-induced BM on rat jejunal contractility. In summary, diprophylline-exerted BM depends on the contractile states of the jejunal segments, requires the presence of $Ca^{2+}$, enteric nervous system, pacemaker activity of interstitial cells of Cajal, and MLCK-correlated myosin phosphorylation. The results suggest the potential implication of diprophylline in relieving alternative hypo/hyper intestinal motility.

Nanotribological behavior of diamond surfaces using molecular dynamics with fractal theory and experiments

Jen-Fin Lin,Te-Hua Fang,Cheng-Da Wu,Ko-Han Houng 한국물리학회 2010 Current Applied Physics Vol.10 No.1

The frictional and indented behavior of a diamond asperity on a diamond plate was carried out using a molecular dynamics (MD) and experiments. The contact load, contact area, dynamic frictional force,and dynamic frictional coefficient increased as the contact interference increased at a constant loading velocity. The microcontact and frictional behavior can be evaluated between a rigid smooth hemisphere to a deformable rough flat plane by combined the deformed behavior of the asperity obtained from MD results with the fractal and statistic parameters. The comparison and the discrepancy of simulated results and nanoindentation and scratching experimental results will be discussed.

Risk Factors for Anxiety in Major Depressive Disorder Patients

Li-Min Xin,Lin Chen,Zhen-Peng Ji,Suo-Yuan Zhang,Jun Wang,Yan-Hong Liu,Da-Fang Chen,Fu-De Yang,Gang Wang,Yi-Ru Fang,Zheng Lu,Hai-Chen Yang,Jian Hu,Zhi-Yu Chen,Yi Huang,Jing Sun,Xiao-Ping Wang,Hui-Chun 대한정신약물학회 2015 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.13 No.3

Objective: To analyze the sociodemographic and clinical factors related to anxiety in patients with major depressive disorder (MDD). Methods: This study involved a secondary analysis of data obtained from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and conducted from September 1, 2010 to February 28, 2011. Based on the presence or absence of anxiety-related characteristics, 1,178 MDD patients were classified as suffering from anxious depression (n=915) or non-anxious depression (n=263), respectively. Results: Compared with the non-anxious group, the anxious-depression group had an older age at onset (t=−4.39, p<0.001), were older (t=−4.69, p<0.001), reported more lifetime depressive episodes (z=−3.24, p=0.001), were more likely to experience seasonal depressive episodes (χ2=6.896, p=0.009) and depressive episodes following stressful life events (χ2=59.350, p <0.001), and were more likely to have a family history of psychiatric disorders (χ2=6.091, p=0.014). Their positive and total scores on the Mood Disorder Questionnaire (MDQ) and the 32-item Hypomania Checklist (HCL-32) (p<0.05) were also lower. The logistic regression analysis indicated that age (odds ratio [OR]=1.03, p<0.001), a lower total MDQ score (OR=0.94, p=0.011), depressive episodes following stressful life events (OR=3.04, p<0.001), and seasonal depressive episodes (OR=1.75, p=0.039) were significantly associated with anxious depression. Conclusion: These findings indicate that older age, fewer subclinical bipolar features, an increased number of depressive episodes following stressful life events, and seasonal depressive episodes may be risk factors for anxiety-related characteristics in patients with MDD.

The characteristics of genistin-induced inhibitory effects on intestinal motility

Yong-jian Xiong,Da-peng Chen,Bo-chao Lv,Fang-fei Liu,Li Wang,Yuan Lin 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.3

Genistin belongs to isoflavones. Based on thefacts that genistin exerts inhibitory effects on the contractilityof vascular smooth muscle,the present study wasdesigned to characterize the effects of genistin on intestinalcontractility and evaluate its potential clinical implication. Ex vivo [isolated jejunal segment (IJS) of rat], in vitro, andin vivo assays were used in the study. The results indicatedthat genistin (5–80 lmol/L) inhibited the contraction of IJSin a dose-dependent manner and inhibited the increasedcontractilityof IJS induced by acetylcholine (ACh), histamine,high Ca2?, and erythromycin, respectively. Theinhibitory effects of genistin were correlated with thestimulation of alpha adrenergic and beta adrenergicreceptors since these inhibitory effects were significantlyblocked in the presence of phentolamine and propranololrespectively. No further inhibitory effects of genistin wereobserved in the presence of verapamil or in Ca2?-freecondition, indicating genistin-induced inhibitory effects areCa2?-dependent. Genistin decreased myosin light chainkinase (MLCK) protein contents and MLCK mRNAexpression in IJS, and inhibited both phosphorylation andMg2?-ATPase activity of purified myosin, implicating thatthe decrease of MLCK contents and inhibition of MLCKactivity are involved in the genistin-induced inhibitoryeffects. The study suggests the potential clinical implicationsof genistin in relieving intestinal hypercontractility.

Changes in Nitrogen and Phosphorus Chemical Structure and Nutrients Release from Raw Biomass to its Converted Biochar

Yu-Hsuan Huang,Chi-Peng Chen,Da-Fang Lin,Chih-Hsin Cheng,Yaw-Wen Yang,Ling-Yun Jang,Oleg Menyailo 한국토양비료학회 2014 한국토양비료학회 학술발표회 초록집 Vol.2014 No.6

Pokemon Inhibits Transforming Growth Factor β-Smad4-Related Cell Proliferation Arrest in Breast Cancer through Specificity Protein 1

Ling Chen,Jing Zhong,Jiang-Hua Liu,Duan-Fang Liao,Ying-Ying Shen,Xiao-Lin Zhong,Xiao Xiao,Wen-Jun Ding,Xiu-Da Peng,Wei Xiong,Xu-Yu Zu 한국유방암학회 2019 Journal of breast cancer Vol.22 No.1

Purpose: Pokemon, also known as ZBTB7A, belongs to the POZ and Krüppel (POK) family of transcription repressors and is implicated in tumor progression as a key proto-oncogene. This present study aimed at determining the mechanism by which Pokemon inhibits transforming growth factor β (TGFβ)-Smad4 pathway-dependent proliferation arrest of breast cancer cells via specificity protein 1 (SP1). Methods: Over-expressing plasmid or small interfering RNA (siRNA) transfection was used to regulate Pokemon levels. The EdU incorporation assay, MTS assay, and clone formation were used to identify the inhibitory effect of Pokemon siRNA on cell proliferation. Quantitative real-time polymerase chain reaction assay confirmed that Pokemon deletion inhibited the expression of proliferation-associated genes. The dual-luciferase reporter assay, electrophoretic mobility shift assay, and co-immunoprecipitation assay were used to analyze binding between Pokemon, Smad4, and SP1. Results: Pokemon deletion induced proliferation arrest of breast cancer cells and inhibited the expression of proliferation-associated genes, especially Smad4. Pokemon bound with SP1 to interdict Smad4 promoter activity. Information on clinical samples was obtained from The Cancer Genome Atlas data, in which the Pokemon mRNA levels showed a negative correlation with Smad4 levels in different subtypes of breast cancer in two independent datasets. Conclusion: We demonstrated that Pokemon binds to SP1 to down-regulate Smad4 expression, thereby promoting proliferation of breast cancer cells. This suggests that Pokemon is a potential TGFβ-signaling participant in breast cancer progression.

MAGED4 Expression in Glioma and Upregulation in Glioma Cell Lines with 5-Aza-2'-Deoxycytidine Treatment

Zhang, Qing-Mei,Shen, Ning,Xie, Sha,Bi, Shui-Qing,Luo, Bin,Lin, Yong-Da,Fu, Jun,Zhou, Su-Fang,Luo, Guo-Rong,Xie, Xiao-Xun,Xiao, Shao-Wen Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

Melanoma-associated antigen (MAGE) family genes have been considered as potentially promising targets for anticancer immunotherapy. MAGED4 was originally identified as a glioma-specific antigen. Current knowledge about MAGED4 expression in glioma is only based on mRNA analysis and MAGED4 protein expression has not been elucidated. In the present study, we investigated this point and found that MAGED4 mRNA and protein were absent or very lowly expressed in various normal tissues and glioma cell line SHG44, but overexpressed in glioma cell lines A172,U251,U87-MG as well as glioma tissues, with significant heterogeneity. Furthermore, MAGED4 protein expression was positively correlated with the glioma type and grade. We also found that the expression of MAGED4 inversely correlated with the overall methylation status of the MAGED4 promoter CpG island. Furthermore, when SHG44 and A172 with higher methylation were treated with the DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR) reactivation of MAGED4 mRNA was mediated by significant demethylation in SHG44 instead of A172. However, 5-AZA-CdR treatment had no effect on MAGED4 protein in both SHG44 and A172 cells. In conclusion, MAGED4 is frequently and highly expressed in glioma and is partly regulated by DNA methylation. The results suggest that MAGED4 might be a promising target for glioma immunotherapy combined with 5-AZA-CdR to enhance its expression and eliminate intratumor heterogeneity.

ABO Blood Group, Epstein-Barr virus Infection and Prognosis of Patients with Non-metastatic Nasopharyngeal Carcinoma

Zhang, Ya-Xiong,Kang, Shi-Yang,Chen, Gang,Fang, Wen-Feng,Wu, Xuan,You, Hua-Jing,He, Da-Cheng,Cao, Ya-Lin,Liang, Wen-Hua,Zhang, Li Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

Background: A prior study showed blood type A/AB to be associated with an increased risk of nasopharyngeal carcinoma (NPC) compared to subjects with blood type O. However, the relationship between ABO blood groups and prognosis of NPC patients is still questionable. In addition, whether Epstein-Barr virus (EBV) infection is associated with prognosis of NPC patients with different ABO blood groups is unclear. Materials and Methods: We conducted univariate and multivariable Cox regression analyses based on a consecutive cohort of 1,601 patients to investigate the above issues. Results: There was no significant difference in overall survival (OS) between different ABO blood groups (p=0.629), neither between A vs. non-A blood groups (p=0.895) nor AB vs. non-AB blood group (p=0.309) in univariate analyses and after adjusting for other factors. Interaction tests revealed that high immunoglobulin A against Epstein-Barr virus viral capsid antigen (VcA-IgA) level was associated with a favorable prognosis in male patients with UICC stage II disease who had an A blood type (p=0.008), compared with those with non-A blood type. In addition, male patients with an A blood group with a high blood lymphocyte level showeda tendency towards better survival in UICC stage III (p=0.096). Conclusions: ABO blood group status is not associated with the prognosis of patients with NPC. Additionally, blood group A male NPC patients with high VcA-IgA level or high blood lymphocyte counts might be correlated with a favorable prognosis in UICC stage II or III, respectively.