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| 1 | Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes:current perspectives and future challenges显示文摘Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body's own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed. | Dinh Ha Ningning Yang Venkatareddy Nadithe | 2016 | Acta Pharmaceutica Sinica B2016，6，4： | 104 |
| 2 | Matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 expression in fibrotic rat liver显示文摘INTRODUCTIONLiver fibrosis is an excessive deposition ofextracellular matrix(ECM)resulted from bothincreased synthesis and decreased degradation.Matrix metalloproteinases(MMPs)represent agroup of neutral proteinases with variable | Liu HL Li XH Wang DY Yang SP | 2000 | World Journal of Gastroenterology2000，6，6： | 31 |
| 3 | Effects of glycyrrhetinic acid on collagen metabolism of hepatic stellate cells at different stages of liver fibrosis in rats显示文摘INTRODUCTIONLiver fibrosis is a dynamic course leading tocirrhosis from a various chronic liver diseases. Thepathological basis of fibrosis is the disturbance ofproduction and degradation of the extracellularmatrix (ECM), which causes accumulation of ECMin the liver[1,2]. | Ji Yao Wang Qi Sheng Zhang Ji Sheng Guo Mei Yu Hu Department of Gastroenterology, Zhongshan Hospital, Medical Center, Fu Dan University Shanghai Medical University), Shanghai 200032, China | 2001 | World Journal of Gastroenterology2001，7，1： | 29 |
| 4 | The regulatory role of AT 1 receptor on activated HSCs in hepat,c fibrogenesis,effects of RAS inhibitors on hepatic fibrosis induced by CCl_4显示文摘AIM To assess the effect of ACE inhibitor andAng Ⅱ type Ⅰ(AT1)receptor antagonist inpreventing hepatic fibrosis caused by CCl4administration in rats;to investigate whether ornot there are expression of AT 1 receptors onhepatic stellate cells;and to observe the effectof Ang Ⅱ on proliferation and ECM synthesis ofcultured HSCs.METHODS Studies were conducted in maleSprague-Dawley rats.Except for thehepatofibrotic model group and the controlgroup,in three treated groups,either enalapril(5 mg/kg),or Iosartan(10 mg/kg),or enalapril+Iosartan were given to the fibrotic rats bydaily gavage,and saline vehicle was given tomodel and normal control rats.After 6 weeks,liver fibrosis was assessed directly by hepaticmorphometric analysis,which has beenconsidered the gold standard for thequantification of fibrosis.The expressions of AT1 receptors and(α-mooth muscle actin,α-SMA)in liver tissue or isolated hepatic stellate cells(HSCs)were detected by immunohistochemicaltechniques.The effect of Ang Ⅱ on HSCproliferation was determined by MTT method.Effect of Ang Ⅱ on collagen synthesis of HSCswas determined by 3H-proline incorporation.RESULTS Contrasted to the fibrosis in rats ofthe model group,groups of rats treated with either enalapril or Iosartan,or a combination oftwo drugs showed a limited expansion of theinterstitium(4.23±3.70 vs 11.22±4.79,P<0.05),but no difference was observedamong three treated groups(5.38±3.43,4.96±2.96,4.23±2.70,P>0.05).Expression of AT 1receptors was found in fibrotic interstitium offibrotic rats,whereas in normal control rats theywere limited to vasculature only to a very slightdegree.AT 1 receptors were also expressed onactivated HSCs in the culture.At concentrationsfrom 10-9to 10-5mol/L,Ang Ⅱ stimulated HSCproliferation in culture in a dose-dependentmanner.Increasing Ang Ⅱ concentrationsproduced corresponding increases in 3H-prolineincorporation.Differences among groups were significant.CONCLUSION Angiotensin-converting enzyme inhibitors and AT I blocker may slow the progression of hepatic fibrosis; activated HSCs express AT 1 receptors, and Ang Ⅱ can stimulate the proliferation and collagen synthesis of HSCs in a dose-dependent manner; and activation of RAS may be related to hepatic fibrogenesis induced by CCI4. | Hong Shan Wei Han Ming Lu Ding Guo Li Yu Tao Zhan Zhi Rong Wang Xin Huang Ji Lin Cheng Qin Fang Xu Department of Gastroenterology,Xinhua Hospital,Shanghai Second Medical University,Shanghai 200092,China | 2000 | World Journal of Gastroenterology2000，6，6： | 27 |
| 5 | Toward a better understanding of microbiologically influenced corrosion caused by sulfate reducing bacteria显示文摘Sulfate reducing bacteria(SRB) are often the culprits of microbiologically influenced corrosion(MIC) in anoxic environments because sulfate is a ubiquitous oxidant. MIC of carbon steel caused by SRB is the most intensively investigated topic in MIC because of its practical importance. It is also because biogenic sulfides complicate mechanistic SRB MIC studies, making SRB MIC of carbon steel is a long-lasting topic that has generated considerable confusions. It is expedient to think that biogenic H_2S secreted by SRB acidifies the broth because it is an acid gas. However, this is not true because endogenous H_2S gets its H^+ from organic carbon oxidation and the fluid itself in the first place rather than an external source. Many people believe that biogenic H_2S is responsible for SRB MIC of carbon steel. However, in recent years,well designed mechanistic studies provided evidence that contradicts this misconception. Experimental data have shown that cathodic electron harvest by an SRB biofilm from elemental iron via extracellular electron transfer(EET) for energy production by SRB is the primary cause. It has been demonstrated that when a mature SRB biofilm is subjected to carbon source starvation, it switches to elemental iron as an electron source and becomes more corrosive. It is anticipated that manipulations of EET related genes will provide genetic-level evidence to support the biocathode theory in the future. This kind of new advances will likely lead to new gene probes or transcriptomics tools for detecting corrosive SRB strains that possess high EET capabilities. | Tingyue Gu Ru Jia Tuba Unsal Dake Xu | 2019 | Journal of Materials Science & Technology2019，35，4： | 28 |
| 6 | Hepatitis B virus X protein up-regulates tumor necrosis factor-α expression in cultured mesangial cells via ERKs and NF-κB pathways显示文摘Objective:To investigate the effects of hepatitis B virus(HBV)X protein(HBx)on the expression of tumor necrosis factor-α(TNF-α)in glomerular mesangial cells(GMCs)and the underlying intracellular signal pathways.Methods:The plasmid pCI-neo-X that carries the X gene of hepatitis B virus was transfected into cultured GMCs.HBx expression in the transfected GMCs was assessed by Western-blot.TNF-αprotein and mRNA were assessed by ELISA and semi-quantitative RT-PCR,respectively.Three kinase inhibitors-U0126,an inhibitor of extracellular signal-regulated kinases(ERKs);lactacvstin,an inhibitor of nuclear factor-κB(NF-κB);and SB203580,a selective inhibitor of p38 MAP kinase(p38 MAPK)were used to determine which intracellular signal pathways may underlie the action of HBx on TNF-αexpression in transfected GMCs.Results:A significant increase in HBx expression in pCI-neo-X transfected GMCs was detected at 36 h and 48 h,which was not affected by any of those kinase inhibitors mentioned above.A similar increase in the expression of both TNF-αprotein and mRNA was also observed at 36 h and 48 h,which was significantly decreased in the presence of U0126 or lactacytin,but not SB203580.Conclusions:HBx upregulates TNF-αexpression in cultured GMCs,possibly through ERKs and NF-κB pathway,but not p38 MAPK pathway. | Hong-Zhu Lu Jian-Hua Zhou | 2013 | Asian Pacific Journal of Tropical Biomedicine2013，3，3： | 16 |
| 7 | Smart scaffolds in bone tissue engineering: A systematic review of literature显示文摘AIM: To improve osteogenic differentiation and attachment of cells.METHODS: An electronic search was conducted inPub Med from January 2004 to December 2013. Studies which performed smart modifications on conventional bone scaffold materials were included. Scaffolds with controlled release or encapsulation of bioactive molecules were not included. Experiments which did not investigate response of cells toward the scaffold(cell attachment, proliferation or osteoblastic differentiation) were excluded. RESULTS: Among 1458 studies, 38 met the inclusion and exclusion criteria. The main scaffold varied extensively among the included studies. Smart modifications included addition of growth factors(group Ⅰ-11 studies), extracellular matrix-like molecules(group Ⅱ-13 studies) and nanoparticles(nano-HA)(group Ⅲ-17 studies). In all groups, surface coating was the most commonly applied approach for smart modification of scaffolds. In group I, bone morphogenetic proteins were mainly used as growth factor stabilized on polycaprolactone(PCL). In group Ⅱ, collagen 1 in combination with PCL, hydroxyapatite(HA) and tricalcium phosphate were the most frequent scaffolds used. In the third group, nano-HA with PCL and chitosan were used the most. As variable methods were used, a thorough and comprehensible compare between the results and approaches was unattainable.CONCLUSION: Regarding the variability in methodology of these in vitro studies it was demonstrated that smart modification of scaffolds can improve tissue properties. | Saeed Reza Motamedian Sepanta Hosseinpour Mitra Ghazizadeh Ahsaie Arash Khojasteh | 2015 | World Journal of Stem Cells2015，7，3： | 15 |
| 8 | Anticoagulant modulation of inflammation in severe sepsis显示文摘Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review examines the interaction between the inflammatory and coagulation cascades, as well as the role of endogenous anticoagulants in regulating this interaction and dampening the activity of both pathways. Clinical trials attempting to improve outcomes in patients with severe sepsis by inhibiting thrombin generation with heparin and or endogenous anticoagulants are reviewed. In general, these trials have failed to demonstrate that anticoagulant therapy is associated with improvement in mortality or morbidity. While it is possible that selective patients who are severelyill with a high expected mortality may be shown to benefit from such therapy, at the present time none of these anticoagulants are neither approved nor can they be recommended for the treatment of sepsis. | Karen S Allen Eva Sawheny Gary T Kinasewitz | 2015 | World Journal of Critical Care Medicine2015，4，2： | 14 |
| 9 | An experimental study of extracellular signal-regulated kinase and its interventional treatments in hepatic fibrosis显示文摘BACKGROUND: The pathogenesis of hepatic fibrosis and cirrhosis is still not fully understood. The extracellular signal-regulated kinase (ERK) pathway is involved in the regulation of cell proliferation and differentiation. The aim of this study was to investigate the effects of PD98059, a specific inhibitor of ERK, on the cell cycle, cell proliferation, secretion of type Ⅰ collagen and expression of cyclin D1 mRNA, CDK4 mRNA and transforming growth factor-β1 (TGF-β1) mRNA in rat hepatic stellate cells (HSCs) stimulated by acetaldehyde. METHODS: Rat HSCs stimulated by acetaldehyde were incubated with PD98059 at different concentrations. The cell cycle was analysed by flow cytometry. Cell proliferation was assessed by the methyl thiazolyl tetrazolium colorimetric assay. The mRNA expression of cyclin D1, CDK4 and TGF-β1 was examined using the reverse transcriptase-polymerase chain reaction. Type Ⅰ collagen in the culture medium was detected by enzyme- linked immunosorbent assay. RESULTS: 20, 50 and 100 μmol/L PD98059 significantly inhibited the proliferation and provoked a G0/G1- phase arrest of acetaldehyde-induced HSCs in a dose- dependent manner. The secretion of type Ⅰ?collagen and the expression of cyclin D1, CDK4 and TGF-β1 mRNA in acetaldehyde-induced HSCs were markedly inhibited by 50 and 100 μmol/L PD98059, respectively.CONCLUSIONS: The ERK pathway regulates the cell proliferation, secretion of type Ⅰ collagen and the expression of TGF-β1 mRNA in rat HSCs stimulated by acetaldehyde, which is likely related to its regulative effect on the cell cycle. | Jiang, Ming-De Zheng, Shu-Mei Xu, Hui Zeng, Wei-Zheng Zhang, Yong Sun, Hao-Ping Wang, Yun-Xia Qin, Jian-Ping Wu, Xiao-Ling | 2008 | Hepatobiliary & Pancreatic Diseases International2008，7，1： | 14 |
| 10 | Role of phosphatase PTEN in the activation of extracellular signal-regulated kinases induced by estradiol in endometrial carcinoma cells显示文摘Objectives To study extracellular signal-regulated kinase (ERK) activation in the endometrial carcinoma cell line Ishikawa with stimulation by 17-β-estradiol, and to elucidate the role of phosphatase and tensin homologue (PTEN) and estrogen receptor (ER) subtype on the activation of ERKs. Methods Western blot was used to examine the expression of PTEN and PTEN (G129E) in Ishikawa cells after stable transfection as well as ERK activation in Ishikawa-EGFP, Ishikawa- PTEN and Ishikawa- PTEN (G129E) stimulated with various doses of 17-β-estradiol for different lengths of time. Western blot was also used for examining the expression of ERα and ERβ in NIH3T3 fibroblasts after transient transfection of pCXN2hERα and pCXN2hERβ. Then, ERK activation was examined after stimulation with 17-β-estradiol. Results 17-β-estradiol activated ERK cascades (mainly ERK2) in Ishikawa cells. The activation of ERK increased gradually as concentration of 17-β-estradiol also increased. The maximal activation of ERK2 took place 5 min after stimulation with 17-β-estradiol. The activation of ERK2 was inhibited markedly by PTEN, but not by PTEN (G129E). 17-β-estradiol activated ERK cascades in NIH3T3 fibroblasts after transient transfection of pCXN2hERα. Conclusions 17-β-estradiol activate ERK cascades in Ishikawa cells by integrating with ERα. Lipid phosphatase PTEN has an inhibitory role on the activation of ERK stimulated by 17-β-estradiol in Ishikawa cells. | 张育军 魏丽惠 王建六 孙铁铮 | 2003 | Chinese Medical Journal2003，，3： | 13 |
| 11 | Plant Immune Mechanisms:From Reductionistic to Holistic Points of View显示文摘After three decades of the amazing progress made on molecular studies of plant-microbe interactions(MPMI),we have begun to ask ourselves'what are the major questions still remaining?'as if the puzzle has only a few pieces missing.Such an exercise has ultimately led to the realization that we still have many more questions than answers.Therefore,it would be an impossible task for us to project a coherent'big picture'of the MPMI field in a single review.Instead,we provide our opinions on where we would like to go in our research as an invitation to the community to join us in this exploration of new MPMI frontiers. | Jie Zhang Gitta Coaker Jian-Min Zhou Xinnian Dong | 2020 | Molecular Plant2020，13，10： | 13 |
| 12 | Shenfu injection attenuates lipopolysaccharide-induced myocardial inflammation and apoptosis in rats显示文摘Shenfu injection(SFI), a Chinese medicinal product, shows potent efficacy in treating sepsis. The aim of the present study was to clarify the protective effects of SFI against lipopolysaccharide(LPS)-induced myocardial inflammation and apoptosis.Experiments were carried out in Sprague-Dawley(SD) rats treated with LPS or LPS + SFI, and in H9 C2 cardiomyocytes. The sepsisassociated myocardial inflammation and apoptosis was induced by the intraperitoneal injection of LPS(20 mg·kg–1). SFI attenuated the increased expression of tumor necrosis factor(TNF)-α and interleukin(IL)-1β induced by LPS both in serum and heart. In LPS group,cell viability was reduced, and reversed after SFI administration. LPS treatment increased the expression levels of cleaved-caspase 3 and Bax, and those of Bcl2 and Bcl2/Bax. These two trends were reversed by SFI administration. The expression levels of phosphorylated mitogen-activated protein kinase kinase(p-MEK) and phosphorylated extracellular regulated protein kinases(p-ERK) were increased by LPS, and reversed by SFI. MEK inhibitor U0126 attenuated the apoptosis induced by LPS. These results indicate that SFI could treat LPS-induced cardiac dysfunction. In conclusion, SFI attenuates the inflammation and apoptosis induced by LPS via downregulating the MEK and ERK signaling pathways. | CHEN Rui-Juan RUI Qing-Lin WANG Qiong TIAN Fang WU Jian KONG Xiang-Qing | 2020 | Chinese Journal of Natural Medicines2020，18，3： | 12 |
| 13 | Exosome-encapsulated miR-505 from ox-LDL-treated vascular endothelial cells aggravates atherosclerosis by inducing NET formation显示文摘Neutrophil extracellular traps(NETs)play an important role in the pathological process of atherosclerosis(AS).This study aims to evaluate whether exosomes from oxidized low-density lipoprotein(ox-LDL)-treated vascular endothelial cells(VECs)aggravate AS by inducing NET formation.Exosomes from the peripheral blood of healthy donors and AS patients(namely NC-EXO and AS-EXO,respectively)and exosomes from human umbilical vein endothelial cells(HUVECs)treated without or with ox-LDL(namely normal EXO and ox-LDL-EXO,respectively)were isolated,identified,and co-cultured with neutrophils from peripheral blood of healthy donors.NET formation was evaluated by immunofluorescence staining and determining the content of cell-free DNA and myeloperoxidase-DNA complex.Dual-luciferase reporter assay,chromatin immunoprecipitation assay,quantitative reverse transcription polymerase chain reaction,and western blot analysis were performed to explore the underlying mechanisms.We found that AS-EXO and ox-LDLEXO in duced NET release from n eutrophils.Meeh a nistically,ox-LDL treatment in HUVECs might activate the NF-κB pathway,which transcriptionally activates miR-505,and then the exosome-encapsulated high miR-505 expression targeted and inhibited SIRT3 in neutrophils,thereby inducing reactive oxygen species(ROS)level increase and NET release by neutrophils.Further in vivo experiments showed that ox-LDLEXO accelerated AS progression in AS mice.In summary,exosome-encapsulated miR-505 from ox-LDLtreated VECs aggravates AS by inducing NET formation. | Li Chen Liqun Hu Qing Li Jian Ma Hongqi Li | 2019 | Acta Biochimica et Biophysica Sinica2019，51，12： | 11 |
| 14 | Prevention of Cistanche salsa Extract on Hepatic Fibrosis Induced by Carbon Tetrachloride in Rats显示文摘Objective To explore the antifibrotic effect of echinacoside on carbon tetrachloride(CCl4)-induced hepatic fibrosis in rats.Methods Male Wistar rats were randomly divided into normal control(n=8),model(n=14),and echinacoside treatment(n=14)groups.The hepatic fibrosis model was induced by CCl4compositor.The rats were ig administered with echinacoside at a daily dose of 50 mg/kg.The anti-oxidant status,liver function parameters,and hepatic hydroxyproline content were detected by chromatometry.The serum levels of hyaluronic acid(HA),type IV collagen(CIV),type III precollagen(PIIIP),and laminin(LN)were assayed with radioimmunoassay.The hpatic injury was detected by haematoxylin-eosine staining.The deposition of collagen was observed with Masson staining.Results Echinacoside increased the superoxide dismutase activity and reduced the levels of malondialdehyde,aspartate aminotransferase,alanine aminotransferase,HA,CIV,PIIIP,and LN in serum.Echinacoside could also reduce the hydroxyproline content in liver,alleviate hepatic injury,and inhibit collagen deposition.Conclusion Echinacoside possesses antihepatic fibrosis effect. | YANG Feng-rui WEN Du-su FANG Bu-wu LOU Jian-shi MENG Lin | 2013 | Chinese Herbal Medicines2013，5，3： | 10 |
| 15 | Effects of sand burial on biomass, chlorophyll fluores-cence and extracellular polysaccharides of man-made cyanobacterial crusts under experimental conditions显示文摘Soil cyanobacterial crusts occur throughout the world, especially in the semiarid and arid regions. It always encounters sand burial, which is an important feature of mobile sand dunes. A greenhouse study was conducted to determine the effects of sand burial on biomass, chlorophyll fluorescence and extracellular polysaccharides of man-made cyanobacterial crusts in six periods of time (0, 5, 10, 15, 20 and 30 d after burying) and at five depths (0, 0.2, 0.5, 1 and 2cm). The results indicated that with the increase of the burial time and burial depth extracellular polysaccharides content and Fv/Fm decreased correspondingly and there were no significant differences between 20 and 30 burial days under dif-ferent burial depths. The degradation of chlorophyll a content appeared only at 20 and 30 burial days and there was also no significant difference between them under different burial depths. It was also observed a simultaneous decrease of the values of the Fv/Fm and the content of extracellular poly-saccharides happened in the crusted cyanobacterium Microcoleus vaginatus Gom. It may suggest that there exists a relationship between extracellular polysaccharides and recovery of the activity of pho-tosystem II (PS II) after rehydration. | WANG WeiBo1,2, YANG CuiYun1,2, TANG DongShan1,2, LI DunHai1, LIU YongDing1& HU ChunXiang1 1 State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China 2 Graduate University of Chinese Academy of Sciences, Beijing 100039, China | 2007 | Science China(Life Sciences)2007，50，4： | 9 |
| 16 | Taking advantage of the potential of mesenchymal stromal cells in liver regeneration:Cells and extracellular vesicles as therapeutic strategies显示文摘Cell-based therapies for acute and chronic liver diseases are under continuous progress. Mesenchymal stem/stromal cells(MSCs) are multipotent cells able to migrate selectively to damaged tissue and contribute to its healing and regeneration. The MSC pro-regenerative effect occurs due to their immunomodulatory capacity and their ability to produce factors that promote cell protection and survival. Likewise,it has been observed that part of their paracrine effect is mediated by MSC-derived extracellular vesicles(EVs). EVs contain proteins,lipids and nucleic acids(DNA,m RNA,mi RNA,lnc RNA) from the cell of origin,allowing for intercellular communication. Recently,different studies have demonstrated that MSC-derived EVs could reproduce,at least in part,the biological effects obtained by MSCbased therapies. Moreover,due to EVs' stability for long periods of time and easy isolation methods they have become a therapeutic option to MSCs treatments. This review summarizes the latest results achieved in clinical trials using MSCs as cell therapy for liver regeneration,the role of EVs in liver physiopathology and the potential of MSC-derived EVs as intercellular mediators and therapeutic tools in liver diseases. | Esteban Juan Fiore Luciana María Domínguez Juan Bayo Mariana Gabriela García Guillermo Daniel Mazzolini | 2018 | World Journal of Gastroenterology2018，24，23： | 9 |
| 17 | Mesenchymal stem cell-derived extracellular vesicles as a new therapeutic strategy for ocular diseases显示文摘Mesenchymal stem cells(MSCs) have attracted considerable attention for their activity in the treatment of refractory visual disorders. Since MSCs were found to possess the beneficial effects by secreting paracrine factors rather than direct differentiation, MSC-derived extracellular vesicles(EVs) were widely studied in various disease models. MSCs generate abundant EVs, which act as important mediators by exchanging protein and genetic information between MSCs and target cells. It has been confirmed that MSC-derived EVs possess unique antiinflammatory, anti-apoptotic, tissue repairing, neuroprotective, and immunomodulatory properties, similar to their parent cells. Upon intravitreal injection, MSC-derived EVs rapidly diffuse through the retina to alleviate retinal injury or inflammation. Due to possible risks associated with MSC transplantation, such as vitreous opacity and pathological proliferation, EVs appear to be a better choice for intravitreal injection. Small size EVs can pass through biological barriers easily and their contents can be modified genetically for optimal therapeutic effect. Hence, currently, they are also explored for the possibility of serving as drug delivery vehicles. In the current review, we describe the characteristics of MSC-derived EVs briefly, comprehensively summarize their biological functions in ocular diseases, and discuss their potential applications in clinical settings. | Bo Yu Xiao-Rong Li Xiao-Min Zhang | 2020 | World Journal of Stem Cells2020，12，3： | 8 |
| 18 | Physiological roles of mitogen-activated-protein-kinase-activated p38-regulated/activated protein kinase显示文摘Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed. | Sergiy Kostenko Gianina Dumitriu Kari Jenssen Lgreid Ugo Moens | 2011 | World Journal of Biological Chemistry2011，2，5： | 8 |
| 19 | Circulating extracellular RNAs,myocardial remodeling,and heart failure in patients with acute coronary syndrome显示文摘Background:Given high on-treatment mortality in heart failure(HF),identifying molecular pathways that underlie adverse cardiac remodeling may offer novel biomarkers and therapeutic avenues.Circulating extracellular RNAs(ex-RNAs)regulate important biological processes and are emerging as biomarkers of disease,but less is known about their role in the acute setting,particularly in the setting of HF.Methods:We examined the ex-RNA profiles of 296 acute coronary syndrome(ACS)survivors enrolled in the Transitions,Risks,and Actions in Coronary Events Center for Outcomes Research and Education Cohort.We measured 374 ex-RNAs selected a priori,based on previous findings from a large population study.We employed a two-step,mechanism-driven approach to identify ex-RNAs associated with echocardiographic phenotypes(left ventricular[LV]ejection fraction,LV mass,LV end-diastolic volume,left atrial[LA]dimension,and LA volume index)then tested relations of these ex-RNAs with prevalent HF(N=31,10.5%).We performed further bioinformatics analysis of microRNA(miRNAs)predicted targets’genes ontology categories and molecular pathways.Results:We identified 44 ex-RNAs associated with at least one echocardiographic phenotype associated with HF.Of these 44 exRNAs,miR-29-3p,miR-584-5p,and miR-1247-5p were also associated with prevalent HF.The three microRNAs were implicated in the regulation p53 and transforming growth factor-βsignaling pathways and predicted to be involved in cardiac fibrosis and cell death;miRNA predicted targets were enriched in gene ontology categories including several involving the extracellular matrix and cellular differentiation.Conclusions:Among ACS survivors,we observed that miR-29-3p,miR-584-5p,and miR-1247-5p were associated with both echocardiographic markers of cardiac remodeling and prevalent HF.Relevance for Patients:miR-29c-3p,miR-584-5p,and miR-1247-5p were associated with echocardiographic phenotypes and prevalent HF and are potential biomarkers for adverse cardiac remodeling in HF. | Khanh-Van Tran Kahraman Tanriverdi Gerard P.Aurigemma Darleen Lessard Mayank Sardana Matthew Parker Amir Shaikh Matthew Gottbrecht Zachary Milstone Selim Tanriverdi Olga Vitseva John F.Keaney Catarina I.Kiefe David D.McManus Jane E.Freedman | 2019 | Journal of Clinical & Translational Research2019，5，1： | 7 |
| 20 | Extracts from Huangqi(Radix Astragali Mongoliciplus) and Ezhu(Rhizoma Curcumae Phaeocaulis) inhibit Lewis lung carcinoma cell growth in a xenograft mouse model by impairing mitogen-activated protein kinase signaling, vascular endothelial growth factor prod显示文摘OBJECTIVE: To study the anti-tumor effects of the extracts from Huangqi(Radix Astragali Mongolici)and Ezhu(Rhizoma Curcumae Phaeocaulis) on the growth of Lewis lung carcinoma(LLC) in a xenograft mouse model and to investigate the possible underlying mechanism.METHODS: LLC tumor-bearing C57 BL/6 mice were treated with normal saline, cisplatin(2 mg/kg intraperitoneally every other day), or Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis)(1∶1, 2∶1, or 3∶1 ratio;5, 8, or 11 g/kg crude drug intragastrically every day) for 15 d.Body weights and tumor volumes were measured every other day. Tumors were excised on day 15 and analyzed. Tumor microvessel density(MVD)was assessed by immunohistochemical staining of CD34;and expression of vascular endothelial cell growth factor(VEGF), the mitogen-activated protein kinases p38 mitogen-activated protein kinase(MAPK), extracellular signal-regulated kinases 1 and 2(ERK1/2), and Jun N-terminal kinase(JNK)and their phosphorylated forms were assessed by Western blotting.RESULTS: Treatment with cisplatin caused a significant loss of body weight compared with controls,whereas Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) extract combinations had no effect. Extracts from Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) significantly decreased tumor weight and tumor MVD compared with controls,and at the 3∶1 treatment group had similar efficacy to cisplatin in reducing MVD. Tumors from Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) treatments also showed decreased p38 MAPK, p-p38 MAPK, ERK1/2, p-ERK1/2,JNK, and p-JNK expression compared with the control group(all P < 0.01). VEGF protein expression was significantly reduced in the 2∶1 and 3∶1 treatment groups compared with the control group(P < 0.01).CONCLUSION: Extracts from Huangqi(Radix Astragali Mongolici) and Ezhu(Rhizoma Curcumae Phaeocaulis) hindered LLC growth in the xenograft mouse model, possibly via inhibition of the MAPK signaling pathway, VEGF production, and tumor angiogenesis. | Xu Chengyong Wang Yuguo Feng Jian Xu Ran Dou Yongqi | 2019 | Journal of Traditional Chinese Medicine2019，39，4： | 7 |
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