Search

Lin Zhang,1,2 Xiaoxu Zhang,1 Yubin Liu,2 Weiyuan Zhang,1 Chu-Tse Wu,2 Lisheng Wang1,3 1Laboratory of Molecular Diagnosis and Regenerative Medicine, the Affiliate Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 3Department of Rehabilitation Sciences, School of Nursing, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Lisheng Wang, Laboratory of Molecular Diagnosis and Regenerative Medicine, the Affiliate Hospital of Qingdao University, Qingdao, 266000, People’s Republic of China, Email lishengwang@qdu.edu.cnBackground: Several studies have shown that MSCs can significantly improve the survival of sepsis animals. CD146+ mesenchymal stem cells (MSCs) correlate with high therapeutic potency. However, their therapeutic effect on sepsis and detail mechanisms have not been explored.Methods: The effect of CD146±MSCs on differentiation of Treg, Th1, Th17 subsets was evaluated by flow cytometry. The effects of CD146±MSCs on RAW264.7 phagocytosis and LPS-stimulated polarization were studied using a co-culture protocol. Luminex bead array and RNA sequencing were employed to determine the mechanisms of MSCs on LPS-stimulated RAW264.7. The Arg1 protein was detected by Western blot. CD146±MSCs were injected into LPS-induced sepsis mice by tail vein. The therapeutic effect was assessed by organ HE staining, T-cell subsets, cytokine in plasma, peritoneal macrophages, infiltrating monocytes subpopulations.Results: In vitro, CD146+MSCs could significantly increase the proportion of Treg cells. Co-culture with CD146+MSCs increase the phagocytic rate of RAW264.7. CD146+MSCs regulate M2-type macrophages production more rapidly. The transcript profile differences between the CD146+MSCs and CD146-MSCs groups were clustered in arginine metabolism pathways. CD146+MSCs decreased NO production and increased ARG1 expression. CD146+MSCs secreted higher level of IL1

Yu-Bin Liu,1,2 Yun Liu,1,3 Lin Zhang,1 Xing-Chen Zhou,1 Bo-Yuan Ren,1 Can Zheng,1 Chun-Hua Hao,4 Wei-Ting Wang,4 Xia Xia,5 Gang-Qiao Zhou,1,3 Chu-Tse Wu,1 Ji-De Jin1 1Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China; 2Division of (Bio) Pharmaceutics, Institute of Zhejiang University - Quzhou, Zhejiang, People’s Republic of China; 3School of Medicine, Guizhou University, Guiyang, People’s Republic of China; 4Center for Pharmacodynamic Research, Tianjin Institute of Pharmaceutical Research, Tianjin, People’s Republic of China; 5Beijing SH Biotechnology Co., Ltd., Beijing, People’s Republic of ChinaCorrespondence: Chu-Tse Wu; Ji-de Jin, Email wuct@bmi.ac.cn; jinjide505@163.comBackground: Whether anticoagulant therapy should be used after spinal-cord injury (SCI) surgery was controversial. The anticoagulation characteristics of a newly developed anticoagulant, recombinant neorudin (EPR-hirudin (EH)), were explored using a rat model of SCI to provide a basis for clinical anticoagulation therapy of SCI.Methods: A rat model of SCI was developed by Allen’s method. Then, thrombosis in the inferior vena cava was induced by ligation. The low-bleeding characteristics of EH were explored by investigating dose–response and time–effect relationships, as well as multiple administration of EH, on thrombus formation complicated with SCI.Results: EH inhibited thrombosis in a dose-dependent manner by reducing the wet weight and dry weight of the thrombus. An inhibiting action of EH on thrombosis was most evident in the group given EH 2 h after SCI. After multiple intravenous doses of EH, thrombosis inhibition was improved to that observed with low molecular weight heparin (LMWH) (87% vs 90%). EH administration after SCI neither increased bleeding in the injured spine nor damaged to nerve function. Bleeding duration and activated partial thromboplastin time were increased in the high-dose

Yu-Bin Liu,1 Lin Zhang,1 Xing-Chen Zhou,1 Ying Zhou,1 Yun Liu,1 Can Zheng,1 Xiao Xu,1 Pan-Pan Geng,1 Chun-Hua Hao,2 Zhuan-You Zhao,2 Chu-Tse Wu,1 Ji-De Jin1 1Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, Beijing, 100850, People’s Republic of China; 2Center for Pharmacodynamic Research, Tianjin Institute of Pharmaceutical Research, Tianjin, 300462, People’s Republic of ChinaCorrespondence: Chu-Tse Wu; Ji-De Jin, Department of Experimental Hematology and Biochemistry, Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing, People’s Republic of China, Tel +86 1086-68158312 ; +86 1086-66931425, Email wuct@bmi.ac.cn; jinjide505@163.comIntroduction: Recombinant neorudin (EPR-hirudin, EH) was developed through the addition of an EPR (Glu-Pro-Arg) peptide to the amino terminus of hirudin, which can be recognized and cut by coagulation factors XIa (FXIa) and/or Xa (FXa). In this study, the low-bleeding antithrombotic effects of EH were evaluated utilizing experimental models of thrombosis in rabbits and rats to provide a test basis for clinical trials.Methods: The bleeding risks of EH and hirudin were first compared in mice by the tail-clipping method, and then the antithrombotic activity of EH was investigated in a rabbit model of arteriovenous bypass thrombosis and a rat model of thrombotic cerebral infarction.Results: In mice, intravenous administration of EH at 1.5 mg/kg and 3 mg/kg did not affect the bleeding time compared with normal saline, while the administration of hirudin at 1.5 mg/kg prolonged the bleeding time by over 3 times the administration of normal saline. Furthermore, intravenous administration of EH had a significant dose-dependent inhibitory effect on the formation and development of arteriovenous bypass thrombosis and thrombotic cerebral infarction. Compared with an equimolar dose of hirudin, the antithrombotic effect of EH was similar, while the bleeding si