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anti-inflammation and anti-fibrosis actions of resveratrol on experimental pneumoconiosis

中国药理学与毒理学杂志 2015年第S1期29卷 61-62页

作者： JieLI Zong-kangZHANG YueQU Wing-NangLEUNG Bao-tingZHANG School of Chinese Medicine Chinese University of Hong Kong Hong Kong SAR China

OBJECTIVE To investigate the therapeutic effects and related signaling pathways involved in the actions of resveratrol on experimental pneumoconiosis in vivo and in *** The pneumoconiosis animal model was induced by exposing male SD rats to 15mg·m-3 silica aerosol in an inhalation chamber system for 6h·d-1,5d·week-1 for up to 8 *** vehicle or resveratrol(10or 20mg·kg-1)was preventively or remedially administered to the rats during or after the 4-or 8-week silica exposure(SE)period,*** 4-,8-,and up to 14-week treatment,in vivo near-infrared fluorescence imaging analysis and histological analysis were performed to evaluate the pathological changes in rat *** cytokines level in bronchoalveolar lavage fluid(BALF)was measured by ELISA testing,and the deposition of fibrotic collagen proteins in lung parenchyma was determined by western blotting and immunohistochemistry *** analysis was performed to screen the signaling pathways involved in the actions of resveratrol on pneumoconiosis in vitro ***-inflammation action and signaling of resveratrol was evaluated on silica-stimulated rat alveolar macrophage,which is one of the crucial effector cells for silica-induced inflammatory response;anti-fibrosis action and signaling of resveratrol was evaluated on TGF-β-induced human lung fibroblast,which acts as a promoter in the later fibrotic process of *** Silica aerosol exposure significantly increased macrophage infiltration and matrix metalloproteinases activity in lung tissue concomitant with the increased levels of inflammatory mediators in *** treatment with resveratrol(20mg·kg-1·d-1)reversed all these biochemical indices as well as histopathological alterations induced by silica ***-SE resveratrol treatment mildly reduced silica-induced inflammatory response in rat lung with no statistical *** vitro study revealed that resveratrol could inhibit alveolar m

关键词： resveratrol anti-inflammation anti-fibrosis pneumo

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An Ac-SDKP analogue resistant to angiotensin converting enzyme exhibits anti-fibrosis effects and improves heart function in mice after myocardial infarction

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Journal of Chinese Pharmaceutical Sciences 2015年第12期24卷 789-800页

作者：陈建辉马晓雯张昭张英启苑媛李萌河南省焦作市中国人民解放军第91中心医院河南焦作454003 第四军医大学西京医院心血管内科陕西西安710032 第四军医大学药学系生物技术中心陕西西安710032

To explore the effect of an Ac-SDKP analog on left ventricular remodeling after myocardial infarction,we synthesized the analog Ac-SD_DK_DP by replacing Asp and Lys with their D *** biological activities of Ac-SD_DK_DP were confirmed using flow cytometry,qRT-PCR,Western blots and fluorescence *** protective effects of Ac-SD_DK_DP on infarcted hearts were assessed in mice with myocardial infarction（MI）.The half-life of Ac-SD_DK_DP was prolonged to over 2 h from a few minutes that Ac-SDKP *** with Ac-SDKP,the analog exhibited stronger inhibition on the differentiation of macrophages,expression of arginase I（ARG I） and TGF-β1 in mature macrophages,proliferation and secretion of collagen type I in cardiac *** MI mice mode,Ac-SD_DK_DP decreased collagen deposition and TGF-β1 expression in myocardium,thus improving the FS（%） to 23.0±7.8 compared with 11.2±6.2 in untreated mice and 11.7±5.3 in Ac-SDKP treated mice（P0.05）.This work shows that the Ac-SDKP analogue is potentially useful for protective treatment for heart failure *** addition,the anti-fibrosis mechanism of Ac-SDKP was correlated with the alternative activation（M2） of macrophages by assessing ARG I and TGF-β1,two important fibrosis-related molecules secreted in M2 macrophages.

关键词： Ac-SDKP Analogue anti-fibrosis Myocardial infarction Heart failure

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25-OCH3-PPD triggers anti-fibrosis activity via c-FLIP-mediated NF-κB activation on activated t-HSC/Cl-6 cells

25-OCH3-PPD triggers anti-fibrosis activity via c-FLIP-media...

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中国药理学会第十一次全国学术会议

作者： WU Yan-ling,WAN Ying,OUYANG Bing-qing,BAI Ting,NAN Ji-xing (Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules,Ministry of Education, College of Pharmacy,Yanbian University,Yanji 133002,China)

25-OCH-PPD is a dammarane-type triterpene sapogenin isolated from the roots,leaves and seeds of ***, which has shown anti-tumor effects in several human cancer *** effects of 25-OCH-PPD on apoptosis of activated t-HSC/Cl-6 cells induced by tumor necrosis factor-α(TNF-α) were *** inhibitory effects of eleven compounds isolated from *** and *** were detected in activated t-HSC/Cl-6 cells.25-OCH-PPD produced a significant inhibitory effect on activated t-HSC /Cl-6 ***,25-OCH-PPD showed almost no effect on the cell viability of Chang liver cells,a type of normal human hepatic cell ***,we aimed to determine the anti-fibrotic potential of 25-OCH-PPD and to characterize the signal transduction pathways involved in activated HSCs.25-OCH-PPD decreased the fibrosis markers,includingα-smooth muscle actin(α-SMA), transforming growth factorβ-1 and tissue inhibitors of metalloproteinases-1(TIMP-1).25-OCH-PPD elevated the level of cellular GSH in activated HSCs,which demonstrated that 25-OCH-PPD might inhibit HSC activation by its antioxidant *** analyses revealed that 25-OCH-PPD increased the levels of cleaved caspase-3,decreased the ratio of Bcl-2/Bax and the expression of sur-vivin via c-FLIP-mediated NF-κB activation and shed light on the regulation of ***,25-OCH-PPD may prove to be an excellent candidate agent for the therapy of hepatic fibrosis.

关键词： 25-OCH3-PPD anti-fibrosis apoptosis c-FLIP NF-kB

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Direct intercellular communications dominate the interaction between adipose-derived MSCs and myofibroblasts aqainst cardiac fibrosis

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Protein & Cell 2015年第10期6卷 735-745页

作者： Xiaokang Li Hui Zhao Chunxiao Qi Yang Zeng Feng Xu Yanan Du Department of Biomedical Engineering School of Medicine Collaborative Innovation Center for Diagnosis and Treament of Infectious Diseases Tsinghua University Beijing 100084 China School of Life Sciences Tsinghua University Beijing 100084 China MOE Key Laboratory Of Biomedical Information E~ngineering School of Life Science and Technology Xi'an Jiaotong University Xi'an 710049 China Bioinspired Engineering and Biomechanics Center (BEBC) Xi'an Jiao Tong University Xi'an 710049 China

The onset of cardiac fibrosis post myocardial infarction greatly impairs the function of heart. Recent advances of cell transplantation showed great benefits to restore myocardial function, among which the mesenchymal stem cells （MSCs） has gained much attention. However, the underlying cellular mechanisms of MSC therapy are still not fully understood. Although paracrine effects of MSCs on residual cardiomyocytes have been discussed, the amelioration of fibrosis was rarely studied as the hostile environment cannot support the survival of most cell populations and impairs the diffusion of soluble factors. Here in order to decipher the potential mecha- nism of MSC therapy for cardiac fibrosis, we investi- gated the interplay between MSCs and cardiac myofibroblasts （mFBs） using interactive co-culture method, with comparison to paracrine approaches, namely treatment by MSC conditioned medium and gap co-culture method. Various fibrotic features of mFBs were analyzed and the most prominent anti-fibrosis effects were always obtained using direct co-culture that allowed cell-to-cell contacts. Hepatocyte growth factor （HGF）, a well-known anti-fibrosis factor, was demonstrated to be a major contributor for MSCs＇ anti-fibrosisfunction. Moreover, physical contacts and tube-like structures between MSCs and mFBs were observed by live cell imaging and TEM which demonstrate the direct cellular interactions.

关键词： cardiac fibrosis stem cell therapy,adipose-derived mesenchymal stem cells myofibroblastscell-to-cell contact anti-fibrosis

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Progress in drug delivery system for fibrosis therapy

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Asian Journal of Pharmaceutical Sciences 2021年第1期16卷 47-61页

作者： Lei Xing Xin Chang Lijun Shen Chenglu Zhang Yatong Fan Chongsu Cho Zhiqi Zhang Hulin Jiang State Key Laboratory of Natural Medicines Department of PharmaceuticsChina Pharmaceutical UniversityNanjing 210009China Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences Seoul National UniversitySeoul 08826Korea Department of General Surgery Shanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200081China

fibrosis is a necessary process in the progression of chronic disease to cirrhosis or even cancer,which is a serious disease threatening human *** studies have shown that the early treatment of fibrosis is turning point and particularly ***,how to reverse fibrosis has become the focus and research hotspot in recent *** far,the considerable progress has been made in the development of effective anti-fibrosis drugs and targeted drug ***,the existing research results will lay the foundation for more breakthrough delivery systems to achieve better anti-fibrosis ***,this review summaries anti-fibrosis delivery systems focused on three major organ fibrotic diseases such as liver,pulmonary,and renal fibrosis accompanied by the elaboration of relevant pathological mechanisms,which will provide inspiration and guidance for the design of fibrosis drugs and therapeutic systems in the future.

关键词： Fibrotic disease Liver fibrosis Lung fibrosis Kidney fibrosis anti-fibrosis Drug delivery system

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Adipose-derived stem cells inhibit dermal fibroblast growth and induce apoptosis in keloids through the arachidonic acid-derived cyclooxygenase-2/prostaglandin E2 cascade by paracrine

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Burns & Trauma 2021年第1期9卷 288-298页

作者： Jinxiu Yang Shiyi Li Leren He Minliang Chen Department of Burn and Plastic Surgery the Fourth Medical CentreChinese People’s Liberation Army General HospitalNo.51 Fucheng RoadHaidian DistrictBeijing100038China Chinese People’s Liberation Army General Hospital No.28 Fuxing RoadHaidian DistrictBeijing100853China 7th Department of Plastic Surgery Plastic Surgery HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNo.33 Ba Dachu RoadShi Jingshan DistrictBeijing100144China

Background:The clinical features of keloids consist of aberrant proliferation,secretion,differentiation and apoptosis of keloid dermis-derived fibroblasts(KFBs).Notably,the apoptosis rate of KFBs is lower than the proliferation *** the anti-fibrotic effect of adipose-derived stem cells(ADSCs)on keloids has become a hot topic of research,the exact anti-fibrotic mechanism of the paracrine effect remains *** study aimed to find out how the conditioned medium of ADSCs(ADSC-CM)exerts an anti-fibrotic effect in ***:KFBs and ADSCs were extracted and ***,ADSC-CM was *** ADSC-CM could inhibit KFB growth and induce apoptosis was verified by the use of a cell counting kit-8,an 5-Ethynyl-2-deoxyuridine(Edu)kit and flow *** expressions of cyclooxygenase-1(COX-1),COX-2,caspase 3 and B-cell lymphoma-2(Bcl-2)in ADSC-CM-cultured KFBs were tested by real-time PCR and western *** clarify the role of COX-2 in ADSC-CM-induced KFB apoptosis,a specific COX-2 inhibitor,celecoxib,was applied to KFBs cultured in ***,we tested the production of arachidonic acid(AA)and prostaglandin E2(PGE2)by ***,we established a keloid transplantation model in a nude mouse to validate the therapeutic effect in ***:The proliferation ability of KFBs cultured in ADSC-CM was found to be weakened and apoptosis was significantly *** 3 expression was significantly upregulated and Bcl-2 was downregulated in ADSC-CM-cultured ***,ADSC-CM strikingly elevated COX-2 mRNA and protein expressions,but COX-1 expression was ***-2 inhibitors reduced ADSC-CM-induced ***,COX-2 inhibition blocked the elevation of caspase 3 and reversed the decrease in Bcl-2 ***-CM increased PGE2 levels by 1.5-fold and this effect was restrained by COX-2 *** the nude mouse model,expressions of AA,COX-2 and PGE2 were higher in the translated keloid tissues after ADSC-CM injecti

关键词： Keloids Adipose-derived stem cells Fibroblasts Apoptosis anti-fibrosis cyclooxygenase-2 Arachidonic acid

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Exosome-mediated aptamer S58 reduces fibrosis in a rat glaucoma filtration surgery model

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International Journal of Ophthalmology(English edition) 2022年第5期15卷 690-700页

作者： Qian-Yi Lin Xiang-Ji Li Yu Leng Xiao-Min Zhu Min Tang Yi Lin Wang-Du Luo Bing-Cai Jiang Xia Chen Lin Xie Department of Ophthalmology The Third Affiliated Hospital of Chongqing Medical UniversityChongqingChina Department of Ophthalmology Daping Hospital of Army Medical UniversityChongqingChina

AIM:To confirm whether exosome-mediated delivery of aptamer S58(Exo-S58) has a better antifibrotic effect than naked S58 in human conjunctival fibroblasts(HCon Fs) and a rat glaucoma filtration surgery(GFS) ***:To enhance the effective reaction time of aptamer S58 in vivo, we loaded aptamer S58 into exosomes derived from HEK293 T cells by PEI transfection to determine the effect of Exo-S58 in HCon Fs and a rat GFS ***:Exo-S58 can significantly reduce cell proliferation, migration and fibrosis in TGF-β2-induced HCon Fs. In an in vivo experiment, Exo-S58 treatment prolonged filtering bleb retention and reduced fibrosis compared with naked S58 treatment in GFS ***:The exosomes are safe and valid carriers to deliver aptamers. Furthermore, Exo-S58 exhibited superior antifibrotic effect than naked S58 both in HCon Fs cells and rat GFS models.

关键词： nanomedicine exosomes aptamer drug delivery glaucoma surgery transforming growth factor-beta anti-fibrosis

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woLiver Regeneration Effect of Oncostatin M Following Hepatectomy for the Rat Cirrhotic Liver Model

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Surgical Science 2012年第11期3卷 530-536页

作者： Naoki Togo Masaki Ueno Kazuhisa Uchiyama Satoru Ozawa Hiroki Yamaue Second Department of Surgery School of Medicine Wakayama Medical University Wakayama Japan

Background/Aims: Liver resection represents the treatment of choice for hepatocellular carcinoma (HCC) arising in well-compensated cirrhosis. Gene expression of the multifunctional cytokine, Oncostatin M (OSM), stimulates liver regeneration and adenoviral vector expressing OSM (AdOSM) allows a persistent expression of the gene. The aim of this study is to evaluate the benefits of the preoperative injection of AdOSM to the remnant lobes to regenerate the liver. Methods: A 70% partial hepatectomy was performed in dimethylnitrosamine-administrated cirrhotic rats with a preoperative injection of AdOSM, adenoviral vector carrying β-galactosidase (AdLacZ), or phosphate-buffered saline (PBS). The morphologic, histologic, and biochemical changes in the remnant liver and survival rates were then assessed. Results: Portal injection with clamping the portal branches of the resected lobes for 5 min made it possible to effectively transduce the adenoviral vector into the remnant lobes. The ratio of the remnant liver weight/body weight (%) was 2.3 ± 0.5 in the AdOSM group, 1.1 ± 0.3 in the AdLacZ group (p fibrosis was 215 ± 141 ng/mL in the AdOSM group and 1963 ± 1225 ng/mL in the AdLacZ group (p = 0.03). Conclusions: The OSM gene therapy may increase the possibility of hepatectomy in a cirrhotic liver by improving fibrosis, hepatic function, and hepatocyte regeneration.

关键词： Oncostatin M Liver Regeneration Cirrhosis anti-fibrosis

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