Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

Yong-Ping Chen,Feng-Bin Lu,Da-Zhi Chen,Lu Chen,En-De Hu,Jin-Lu Wu,Hui Li,Yue-Wen Gong,Zhuo Lin,Xiao-Dong Wang,Ji Li,Xiao-Ya Jin,Lan-Man Xu 한국분자세포생물학회 2019 Molecules and cells Vol.42 No.12

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p

Lu, Feng-Bin,Chen, Da-Zhi,Chen, Lu,Hu, En-De,Wu, Jin-Lu,Li, Hui,Gong, Yue-Wen,Lin, Zhuo,Wang, Xiao-Dong,Li, Ji,Jin, Xiao-Ya,Xu, Lan-Man,Chen, Yong-Ping Korean Society for Molecular and Cellular Biology 2019 Molecules and cells Vol.42 No.12

MicroRNA-223-3p (miR-223-3p) is one of the potential microRNAs that have been shown to alleviate inflammatory responses in pre-clinical investigations and is highly encased in exosomes derived from bone mesenchymal stem cells (MSC-exosomes). MSC-exosomes are able to function as carriers to deliver microRNAs into cells. Autoimmune hepatitis is one of the challenging liver diseases with no effective treatment other than steroid hormones. Here, we examined whether MSC-exosomes can transfer miR-223-3p to treat autoimmune hepatitis in an experimental model. We found that MSC-exosomes were successfully incorporated with miR-223-3p and delivered miR-223-3p into macrophages. Moreover, there was no toxic effect of exosomes on the macrophages. Furthermore, treatments of either exosomes or exosomes with miR-223-3p successfully attenuated inflammatory responses in the liver of autoimmune hepatitis and inflammatory cytokine release in both the liver and macrophages. The mechanism may be related to the regulation of miR-223-3p level and STAT3 expression in the liver and macrophages. These results suggest that MSC-exosomes can be used to deliver miR-223-3p for the treatment of autoimmune hepatitis.

IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1−/−Mice Mediated by miR-33

Chen-Yi Tang,Xiao-Fei Man,Yue Guo,Hao-Neng Tang,Jun Tang,Ci-La Zhou,Shu-Wen Tan,Min Wang,Hou-De Zhou 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.2

Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse (Irs-1−/−) with growth retardation and subcutaneous adipocyte atrophy. Irs-1−/− mice exhibited mild insulin resistance, as demonstrat-ed by the insulin tolerance test. Phosphatidylino-sitol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcu-taneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of Irs-1−/− mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What’s more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of Irs-1−/− mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

An Unprecedented 3D Self-catenated Four-coordinated Dense Net of Silver-Organic Framework

Xiao, Shu-Lin,Cui, Guang-Hua,Blatov, Vladislav A.,Geng, Jian-Chen,Li, Guang-Yue Korean Chemical Society 2013 Bulletin of the Korean Chemical Society Vol.34 No.6

Structural and optical investigation of GaN grown by metal-organic Chemical Vapor Deposition

Xiao-Yong Gao,Liang-Yao Chen,Jing Li,Peng Zhou,Rong-Jun Zhang,Song-You Wang,Yue-Mei Yang,Yu-Xiang Zheng 한국물리학회 2004 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.44 No.32

Structural and optical properties of GaN grown on (0001)-oriented sapphire substrates by low pressure metal-organic chemical vapor deposition were investigated by XRD, ellipsometry, PL and other optical methods. The thickness of the GaN sample was about 1.5 m. Seen by XRD, the existence of the strong (0002) diraction peak with a very narrow FWHM value of 0.1 and the high order GaN (0004) diraction peak conrms a good quality of the GaN lms grown on sapphire substrate by using a multi-step growth procedure. Optical transparency of the GaN samples induces strong interference oscillations below E0 (3.44eV) in the measured dielectric function spectra and re ective spectra. In low temperature PL spectra, the red shift of the peak and decreased intensity of PL are visible. The former can be attributed to the involvement of band tail states, and the latter can be accounted for by the decreasing non-radiative recombination lifetime.

Path Tracking Control of Skid-steered Mobile Robot on the Slope Based on Fuzzy System and Model Predictive Control

Xiao Yue,Jiankui Chen,Yiqun Li,Rong Zou,Zhihao Sun,Xiaochuan Cao,Song Zhang 제어·로봇·시스템학회 2022 International Journal of Control, Automation, and Vol.20 No.4

Skid-steered mobile robots are often used in outdoor exploration due to their robust mechanical structure and high maneuverability. When they track reference path on a slope with boundaries, ensuring the tracking accuracy and stability of the skid-steered mobile robot is the major target. However, the gravity makes the relationship between wheels and ground more complex on the slope, and variational slope angle also makes it difficult for tracking control. The common control methods focus on plane motion, where only the plane forces are taken into account and the gravity is normally ignored. It may lead to some performance limitations such as the accuracy of motion on a slope. To address these problems, a model predictive control strategy combined with a fuzzy system is proposed in this paper, which has considered the dynamics of the body and wheels on the slope. We improved the two dimensional kinematics and dynamics model of the robot, which makes the three dimensional motion control more accurate. And the control method allows the robot to adapt to slopes with different angles and to make the path tracking stable to curvature mutation. Both experiment and simulation results demonstrate the effectiveness and superiority of the proposed model and method.

Experimental and Numerical Investigation on the Dynamic Responses of the Remaining Structure under Impact Loading with Column Being Removed

Chen Ou,Jun Liu,Lei Sun,Zhi-min Xiao,Yi Cheng,Ming-qing Liu,Fu-tian Zhao,Meng-yang Zhen,Yue Wang 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.6

The dynamic response and stability of building structures under accidental loads such as earthquake, explosion, and impact have been focused by experts. The significant influence will be induced once the damaged structure begins to collapse. In this study, a reinforced concrete frame structure model was designed and tested to study the dynamic response law of the structure under the condition of the failure of the middle column of the model structure, the remaining structure successively failed the load-bearing column and continued to be subjected to impact load and uniform load. The analytical method was used to calculate the ultimate uniform load subjecting to the structure under the failure of four load-bearing columns, because its value was less than the load in this test, the structure collapsed. The finite element calculation model was established, and compared the simulation results to the test results to verify its rationality. Then, the influence of the impact energy and the structural stores on the dynamic response of the structure were analyzed. The results showed that the peak value of the dynamic response of the damaged structure did not increase strictly with the increase of the number of failure columns, which may be related to the sequence of failure columns.

Chinese herbal medicine for drug-induced liver injury in patients with HIV/AIDS: A systematic review of randomized controlled trials

Zhang Xiao-wen,Li Jing,Hou Wen-Bin,Jiang Yue,Zheng Ruo-Xiang,Xu De-hao,Shen Chen,Robinson Nicola,Liu Jian-Ping 한국한의학연구원 2023 Integrative Medicine Research Vol.12 No.1

Background: To explore the effectiveness and safety of Chinese herbal medicine (CHM) for drug-induced liver injury (DILI) in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syn- drome (AIDS). Methods: A systematic search was made of eight databases (Pubmed, Cochrane Library, Web of Science, Embase, CNKI, Wanfang, VIP, Sinomed) and two trial registries (WHO ICTRP, ClinicalTrials.gov) from in- ception to September 2022. The effect size was presented as risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI). The Cochrane Risk of Bias and Grading of Recommendations, Assess- ment, Development and Evaluations (GRADE) tools were used for quality appraisal. Results: Ten randomized controlled trials (RCTs) involving 732 participants were included. Comparing CHM alone with routine treatment, the CHM group showed lower aspartate aminotransferase (MD = -11.47 U/L, 95%CI[-13.05, -9.89], low certainty), lower alanine aminotransferase (MD = -2.68 U/L, 95%CI[-4.27, - 1.08], low certainty), lower total bilirubin (MD = -4.31 mmol/L, 95%CI[-5.66, -2.96], low certainty), lower bilirubin direct (MD = -3.19 mmol/L, 95%CI[-3.87, -2.51], low certainty), and higher effective rate (assessed by symptoms and liver indicators) (RR = 1.13, 95%CI[1.06, 1.20], low certainty). A significant difference was also found in CHM plus routine treatment versus routine treatment in the previous outcomes. No signif- icant difference was found on helper T cells among these comparisons. Only one RCT reported safety of CHM and found no adverse reaction during the trial. Conclusions: CHM may improve the liver function indices and effective rate for HIV/AIDS patients with DILI. However, the sample size was small and quality was low. Larger-samples of high-quality trials are needed.

Clinical Prognostic Factors in 86 Chinese Patients with Primary Myelodysplastic Syndromes and Trisomy 8: A Single Institution Experience

Xin-Yue Liu,Qing-Fang Yue,Lei Chen,Xiao-Mei She,Bin Hu,Yu Hu,Ping Zou 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.2

Purpose: The objective was to determine the characteristics and prognostic factors of 86 Chinese patients with trisomy 8 aberrationsand compare the prognostic value of International Prognostic System (IPSS) and Revised IPSS (IPSS-R) in this cohort. Materials and Methods: A total of 86 cases diagnosed with primary myelodysplastic syndromes (MDS) with isolated tr8 or with tr8 and other additional cytogenetic aberrations diagnosed and treated at the Union Hospital, Tongji Medical College of Huazhong University of Science and Technology between July 2002 and March 2013 were reviewed. Results: The median survival of the entire group was 23.0 months, and acute myeloid leukemia (AML) developed in 43% (37/86) patients within the follow up time. The univariate analysis revealed that overall survival (OS) was correlated with age, thrombocytopenia,absolute neutrophil count, marrow blasts, cytogenetic status and red blood cell transfusion at diagnosis, and the multivariateanalysis revealed that age, marrow blasts, cytogenetic status and transfusion dependence were independent parameters for the OS. The cytogenetic complexity and marrow blasts had the strongest impact on the AML transformation by multivariate analysis. Comparing the two prognostic systems, both two systems could successfully discriminate risk groups for survival. IPSS-R was more refined than IPSS for predicting OS, but had no advantage in predicting the risk of AML development. Conclusion: This study confirmed the influence of clinical factors on the prognosis of 86 Chinese MDS patients with trisomy 8. In addition, IPSS-R can further refine prognostic discrimination in the IPSS risk categories.

IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1^-/- Mice Mediated by miR-33

Tang, Chen-Yi,Man, Xiao-Fei,Guo, Yue,Tang, Hao-Neng,Tang, Jun,Zhou, Ci-La,Tan, Shu-Wen,Wang, Min,Zhou, Hou-De Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.2

Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse ($Irs-1^{-/-}$) with growth retardation and subcutaneous adipocyte atrophy. $Irs-1^{-/-}$ mice exhibited mild insulin resistance, as demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of $Irs-1^{-/-}$ mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What's more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of $Irs-1^{-/-}$ mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.