HCV, Acute, LT : A Disparate Subset of Double Negative T cells Contributes to the Outcome of Murine Fulminant Viral Hepatitis via Effector Molecule Fibrinogen-like Protein 2

( Di Wu ),( Hong Wu Wang ),( Tao Chen ),( Yong Zou ),( Wei Ming Yan ),( Mei Fang Han ),( Ze Guang Wu ),( Xiao Jing Wang ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Aims: The underlying pathogenesis of fulminant viral hepatitis (FVH) has not been fully elucidated. As a subset of regulatory T cells, CD3+CD4-CD8- double negative (DN) T cells can suppress T cell responses. In this study, we present new insights into the immune mediated mechanisms involved in FVH caused by murine hepatitis virus strain 3 (MHV-3). Methods: The phenotype and cytokines of DN T cells were detected by flow cytometric analysis. The levels of mfgl2 were measured by real-time PCR and western-blot. The function of mfgl2 was measured by PCA. Results: After MHV-3 infection, the proportions of DN T cells increased significantly in BALB/cJ mice, and splenic DN T cells expressing high levels of CD69 were recruited by MHV-3 infected hepatocytes to the liver. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) increased, accompanied by massive hepatocyte necrosis. These DN T cells were predominantly consisted of a TCRαβ+ subset expressing high levels of CD44, and did not produce cytokine except IL-2. Adoptive transfer of this subset of DN T cells to the MHV-3 infected mice resulted in an increase of murine fibrinogen-like protein 2 (mfgl2) expression in association with massive fibrin deposition in the liver. Following MHV-3 infection, membrane mfgl2 expression and functional procoagulant activity (PCA) increased remarkably in the DN T cells. Introduction of a recombinant adenovirus which encoded a microRNA specifically targeting mfgl2 gene (Ad-mfgl2-miRNA) in vivo significantly inhibited the hepatic expression of mfgl2, increased mice survival. However, under this condition, adoptive transfer of the DN T cells accelerated the disease progression and reversed the benefit from mfgl2 gene silence, led to a 100% death. Conclutions: Our results demonstrated that DN T cell-derived mfgl2 may serve as an important effector molecule contributing to the pathogenesis of MHV-3-induced FVH.

Casein Kinase 2 interacts with human mitogen- and stress-activated protein kinase MSK1 and phosphorylates it at Multiple sites

( Yan Shi ),( Guang Hui Han ),( Hui Ling Wu ),( Kan Ye ),( Zhi Peng Tian ),( Jia Qi Wang ),( Hui Li Shi ),( Ming Liang Ye ),( Han Fa Zou ),( Ke Ke Huo ) 생화학분자생물학회 2009 BMB Reports Vol.42 No.12

Association between the MDM2 T309G Polymorphism and Leukemia Risk: a Meta-analysis

Yan, Yu-Lan,Han, Feng,Tan, Wen-Min,Wu, Cui-Ping,Qin, Xi Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Several studies have suggested associations between MDM2 (mouse double minute 2 homolog) polymorphisms and leukemia risk, but they reported contradictory results. For better understanding of the effect of MDM2 T309G polymorphism on leukemia risk, we performed a meta-analysis. All eligible studies were identified through a search of PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature (CBM) databases before May 2014. Assessment of associations between the MDM2 T309G polymorphism and leukemia risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). Finally, a total of 11 publications covering 12 case-control studies with 2, 362 cases and 5, 562 controls concerning MDM2 T309G polymorphism with respect to leukemia were included in the meta-analysis. Significant associations were found between MDM2 T309G polymorphism and leukemia risk in four models in overall populations (G vs T: OR=1.29, 95% CI=1.11-1.49, p=0.001; GG vs TT: OR=1.67, 95% CI=1.21-2.30, p=0.002; GG vs TG/TT: OR=1.56, 95% CI=1.21-2.00, p=0.001; GG/TG vs TT: OR=1.28, 95% CI=1.05-1.57, p=0.015). In the sub-group analysis according to ethnicity, increased leukemia risks were observed in three genetic models among Asians but not Caucasians. In conclusion, the results of our meta-analysis suggest that the MDM2 T309G polymorphism can increase the risk of leukemia, especially among Asian populations.

A unique cytoplasmic localization of retinoic acid receptor-gamma and its regulations.

Han, Young-Hoon,Zhou, Hu,Kim, Jin-Hee,Yan, Ting-dong,Lee, Kee-Ho,Wu, Hua,Lin, Feng,Lu, Na,Liu, Jie,Zeng, Jin-zhang,Zhang, Xiao-kun American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.27

<P>Recent evidence suggests that extranuclear action of retinoid receptors is involved in mediating the pleiotropic effects of retinoids. However, whether they reside in the cytoplasm remains elusive. Here, we showed that retinoic acid receptor-gamma (RARgamma) was cytoplasmic in confluent cells, or when cells were released from serum depletion or treated with growth factors. In studying the regulation of RARgamma subcellular localization, we observed that ectopically overexpressed RARgamma was mainly cytoplasmic irrespective of serum concentration and cell density. The cytoplasmic retention of RARgamma was inhibited by ligand retinoic acid (RA). In addition, coexpression of retinoid X receptor-alpha (RXRalpha) resulted in nuclear localization of RARgamma through their heterodimerization. Mutagenesis studies revealed that a C-terminal fragment of RXRalpha potently prevents RA-induced RARgamma nuclear localization and transcriptional function. Furthermore, our results showed that the cytoplasmic retention of RARgamma was due to the presence of its unique N-terminal A/B domain, which was subject to regulation by p38 MAPK-mediated phosphorylation. Deletion or mutation of the N-terminal A/B domain largely impaired its cytoplasmic localization. Together, our data demonstrate that the subcellular localization of RARgamma is regulated by complex interactions among ligand binding, receptor phosphorylation, and receptor dimerizations.</P>

The role of extracellular vesicles in osteoarthritis treatment via microenvironment regulation

Han Yin,Muzhe Li,Guangzhao Tian,Yang Ma,Chao Ning,Zineng Yan,Jiang Wu,Qian Ge,Xiang Sui,Shu-Yun Liu,Jinxuan Zheng,Weimin Guo,Quan-Yi Guo 한국생체재료학회 2022 생체재료학회지 Vol.26 No.4

Osteoarthritis (OA) is a degenerative joint disease that is common among the middle-aged and older populations, causes patients to experience recurrent pain in their joints and negatively affects their quality of life. Currently, therapeutic options for patients with OA consist of medications to alleviate pain and treat the symptoms; however, due to typically poor outcomes, patients with advanced OA are unlikely to avoid joint replacement. In recent years, several studies have linked disrupted homeostasis of the joint cavity microenvironment to the development of OA. Recently, extracellular vesicles (EVs) have received increasing attention in the field of OA. EVs are natural nano-microcarrier materials with unique biological activity that are produced by cells through paracrine action. They are composed of lipid bilayers that contain physiologically active molecules, such as nucleic acids and proteins. Moreover, EVs may participate in local and distal intercellular and intracellular communication. EVs have also recently been shown to influence OA development by regulating biochemical factors in the OA microenvironmental. In this article, we first describe the microenvironment of OA. Then, we provide an overview of EVs, summarize the main types used for the treatment of OA, and describe their mechanisms. Next, we review clinical studies using EVs for OA treatment. Finally, the specific mechanism underlying the application of miRNA-enriched EVs in OA therapy is described.

A fiber beam element model for elastic-plastic analysis of girders with shear lag effects

Wu-Tong Yan,Bing Han,Li Zhu,Yu-Ying Jiao,Hui-bing Xie 국제구조공학회 2019 Steel and Composite Structures, An International J Vol.32 No.5

This paper proposes a one-dimensional fiber beam element model taking account of materially non-linear behavior, benefiting the highly efficient elastic-plastic analysis of girders with shear-lag effects. Based on the displacement-based fiber beam-column element, two additional degrees of freedom (DOFs) are added into the proposed model to consider the shear-lag warping deformations of the slabs. The new finite element (FE) formulations of the tangent stiffness matrix and resisting force vector are deduced with the variational principle of the minimum potential energy. Then the proposed element is implemented in the OpenSees computational framework as a newly developed element, and the full Newton iteration method is adopted for an iterative solution. The typical materially non-linear behaviors, including the cracking and crushing of concrete, as well as the plasticity of the reinforcement and steel girder, are all considered in the model. The proposed model is applied to several test cases under elastic or plastic loading states and compared with the solutions of theoretical models, tests, and shell/solid refined FE models. The results of these comparisons indicate the accuracy and applicability of the proposed model for the analysis of both concrete box girders and steel-concrete composite girders, under either elastic or plastic states.

Experimental study on creep behavior of fly ash concrete filled steel tube circular arches

Wu T. Yan,Bing Han,Jin Q. Zhang,Hui B. Xie,Li Zhu,Zhong J. Xue 국제구조공학회 2018 Steel and Composite Structures, An International J Vol.27 No.2

Fly ash can significantly improve concrete workability and performance, and recycling fly ash in concrete can contribute to a cleaner environment. Since fly ash influences pozzolanic reactions in concrete, mechanical behaviors of concrete containing fly ash differ from traditional concrete. Creep behaviors of fly ash concrete filled steel tube arch were experimentally investigated for 10% and 30% fly ash replacement. The axes of two arches are designed as circular arc with 2.1 m computed span, 0.24 m arch rise, and their cross-sections are all in circular section. Time dependent deflection and strain of loading and mid-span steel tube were measured, and long term deflection of the model arch with 10% fly ash replacement was significantly larger than with 30% replacement. Considering the steel tube strain, compressive zone height, cross section curvature, and internal force borne by the steel tube, the compressive zone height and structural internal forces increased gradually over time due to concrete creep. Increased fly ash content resulted in more significant neutral axis shift. Mechanisms for internal force effects on neutral axis height were analyzed and verified experimentally.

Proposals for flexural capacity prediction method of externally prestressed concrete beam

Wu-Tong Yan,Liang-Jiang Chen,Bing Han,Feng Wei,Hui-Bing Xie,Jia-Ping Yu 국제구조공학회 2022 Structural Engineering and Mechanics, An Int'l Jou Vol.83 No.3

Flexural capacity prediction is a challenging problem for externally prestressed concrete beams (EPCBs) due to the unbonded phenomenon between the concrete beam and external tendons. Many prediction equations have been provided in previous research but typically ignored the differences in deformation mode between internal and external unbonded tendons. The availability of these equations for EPCBs is controversial due to the inconsistent deformation modes and ignored secondorder effects. In this study, the deformation characteristics and collapse mechanism of EPCB are carefully considered, and the ultimate deflected shape curves are derived based on the simplified curvature distribution. With the compatible relation between external tendons and the concrete beam, the equations of tendon elongation and eccentricity loss at ultimate states are derived, and the geometric interpretation is clearly presented. Combined with the sectional equilibrium equations, a rational and simplified flexural capacity prediction method for EPCBs is proposed. The key parameter, plastic hinge length, is emphatically discussed and determined by the sensitivity analysis of 324 FE analysis results. With 94 collected laboratory-tested results, the effectiveness of the proposed method is confirmed, and comparisons with the previous formulas are made. The results show the better prediction accuracy of the proposed method for both stress increments and flexural capacity of EPCBs and the main reasons are discussed.

PGC-1<i>α</i> Protects from Notch-Induced Kidney Fibrosis Development

Han, Seung Hyeok,Wu, Mei-yan,Nam, Bo Young,Park, Jung Tak,Yoo, Tae-Hyun,Kang, Shin-Wook,Park, Jihwan,Chinga, Frank,Li, Szu-Yuan,Susztak, Katalin American Society of Nephrology 2017 Journal of the American Society of Nephrology Vol.28 No.11

Hierarchical porous ECM scaffolds incorporating GDF-5 fabricated by cryogenic 3D printing to promote articular cartilage regeneration

Wu Jiang,Fu Liwei,Yan Zineng,Yang Yu,Yin Han,Li Pinxue,Yuan Xun,Ding Zhengang,Kang Teng,Tian Zhuang,Liao Zhiyao,Tian Guangzhao,Ning Chao,Li Yuguo,Sui Xiang,Chen Mingxue,Liu Shuyun,Guo Quanyi 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

In recent years, there has been significant research progress on in situ articular cartilage (AC) tissue engineering with endogenous stem cells, which uses biological materials or bioactive factors to improve the regeneration microenvironment and recruit more endogenous stem cells from the joint cavity to the defect area to promote cartilage regeneration.In this study, we used ECM alone as a bioink in low-temperature deposition manufacturing (LDM) 3D printing and then successfully fabricated a hierarchical porous ECM scaffold incorporating GDF-5.Comparative in vitro experiments showed that the 7% ECM scaffolds had the best biocompatibility. After the addition of GDF-5 protein, the ECM scaffolds significantly improved bone marrow mesenchymal stem cell (BMSC) migration and chondrogenic differentiation. Most importantly, the in vivo results showed that the ECM/GDF-5 scaffold significantly enhanced in situ cartilage repair.In conclusion, this study reports the construction of a new scaffold based on the concept of in situ regeneration, and we believe that our findings will provide a new treatment strategy for AC defect repair.