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1Hepatic fibrosis: It is time to go with hepatic stellate cell-specifictherapeutic targets显示文摘Hepatic fibrosis is a pathological lesion, characterized by the progressive accumulation of extracellular matrix(ECM) in the perisinusoidal space and it is a major problem in chronic liver diseases. Phenotypic activation of hepatic stellate cells(HSC) plays a central role in the progression of hepatic fibrosis. Retardation of proliferation and clearance of activated HSCs from the injured liver is an appropriate therapeutic strategy for the resolution and treatment of hepatic fibrosis. Clearance of activated HSCs from the injured liver by autophagy inhibitors, proapoptotic agents and senescence inducers with the high affinity toward the activated HSCs may be the novel therapeutic strategy for the treatment of hepatic fibrosis in the near future.Devaraj Ezhilarasan Etienne Sokal Mustapha Najimi 2018Hepatobiliary & Pancreatic Diseases International2018,17,3:56
2Stem cells for liver tissue repair:Current knowledge and perspectives显示文摘Stem cells from extra-or intrahepatic sources have been recently characterized and their usefulness for the generation of hepatocyte-like lineages has been demonstrated. Therefore, they are being increasingly considered for future applications in liver cell therapy. In that field, liver cell transplantation is currently regarded as a possible alternative to whole organ transplantation, while stem cells possess theoretical advantages on hepatocytes as they display higher in vitro culture performances and could be used in autologous transplant procedures. However, the current research on the hepatic fate of stem cells is still facing difficulties to demonstrate the acquisition of a full mature hepatocyte phenotype, both in vitro and in vivo. Furthermore, the lack of obvious demonstration of in vivo hepatocyte-like cell functionality remains associated to low repopulation rates obtained after current transplantation procedures. The present review focuses on the current knowledge of the stem cell potential for liver therapy. We discuss the characteristics of the principal cell candidates and the methods to demonstrate their hepatic potential in vitro and in vivo. We finally address the question of the future clinical applications of stem cells for liver tissue repair and the technical aspects that remain to be investigated.Philippe A Lysy David Campard Fran oise Smets Mustapha Najimi Etienne M Sokal 2008World Journal of Gastroenterology2008,14,6:22
3Use of mesenchymal stem cells to treat liver fibrosis:Current situation and future prospects显示文摘Progressive liver fibrosis is a major health issue for which no effective treatment is available,leading to cirrhosis and orthotopic liver transplantation.However,organ shortage is a reality.Hence,there is an urgent need to find alternative therapeutic strategies.Cellbased therapy using mesenchymal stem cells(MSCs) may represent an attractive therapeutic option,based ontheir immunomodulatory properties,their potential to differentiate into hepatocytes,allowing the replacement of damaged hepatocytes,their potential to promote residual hepatocytes regeneration and their capacity to inhibit hepatic stellate cell activation or induce their apoptosis,particularly via paracrine mechanisms.The current review will highlight recent findings regarding the input of MSC-based therapy for the treatment of liver fibrosis,from in vitro studies to pre-clinical and clinical trials.Several studies have shown the ability of MSCs to reduce liver fibrosis and improve liver function.However,despite these promising results,some limitations need to be considered.Future prospects will also be discussed in this review.Silvia Berardis Prenali Dwisthi Sattwika Mustapha Najimi Etienne Marc Sokal 2015World Journal of Gastroenterology2015,21,3:22
4Liver cell transplantation for Crigler-Najjar syndrome type Ⅰ: Update and perspectives显示文摘Liver cell transplantation is an attractive technique to treat liver-based inborn errors of metabolism. The feasibility and efficacy of the procedure has been demonstrated, leading to medium term partial metabolic control of various diseases. Crigler-Najjar is the paradigm of such diseases in that the host liver is lacking one function with an otherwise normal parenchyma. The patient is at permanent risk for irreversible brain damage. The goal of liver cell transplantation is to reduce serum bilirubin levels within safe limits and to alleviate phototherapy requirements to improve quality of life. Preliminary data on Gunn rats, the rodent model of the disease, were encouraging and have led to successful clinical trials. Herein we report on two additional patients and describe the current limits of the technique in terms of durability of the response as compared to alternative therapeutic procedures. We discuss the future developments of the technique and new emerging perspectives.Philippe A Lysy Mustapha Najimi Xavier Stéphenne Annick Bourgois Franoise Smets Etienne M Sokal 2008World Journal of Gastroenterology2008,14,22:9
5Hepatocyte cryopreservation:Is it time to change the strategy?显示文摘Liver cell transplantation presents clinical benefit in patients with inborn errors of metabolism as an alternative,or at least as a bridge,to orthotopic liver transplantation.The success of such a therapeutic approach remains limited by the quality of the transplanted cells.Cryopreservation remains the best option for long-term storage of hepatocytes,providing a permanent and sufficient cell supply.However, isolated adult hepatocytes are poorly resistant to such a process,with a significant alteration both at the morphological and functional levels.Hence,the aim of the current review is to discuss the state of the art regarding widely-used hepatocyte cryopreservation protocols,as well as the assays performed to analyse the post-thawing cell quality both in vitro and in vivo. The majority of studies agree upon the poor quality and efficiency of cryopreserved/thawed hepatocytes as compared to freshly isolated hepatocytes.Intracellular ice formation or exposure to hyperosmotic solutionsremains the main phenomenon of cryopreservation process,and its effects on cell quality and cell death induction will be discussed.The increased knowledge and understanding of the cryopreservation process will lead to research strategies to improve the viability and the quality of the cell suspensions after thawing.Such strategies,such as vitrification,will be discussed with respect to their potential to significantly improve the quality of cell suspensions dedicated to liver cell-based therapies.Xavier Stéphenne Mustapha Najimi Etienne M Sokal 2010World Journal of Gastroenterology2010,16,1:9
6Silibinin induces hepatic stellate cell cycle arrest via enhancing p53/p27 and inhibiting Akt downstream signaling protein expression显示文摘BACKGROUND: Proliferation of hepatic stellate cells(HSCs) plays a pivotal role in the progression of liver fibrosis consequent to chronic liver injury. Silibinin, a flavonoid compound,has been shown to possess anti-fibrogenic effects in animal models of liver fibrosis. This was attributed to an inhibition of cell proliferation of activated HSCs. The present study was to gain insight into the molecular pathways involved in silibinin anti-fibrogenic effect. METHODS: The study was conducted on LX-2 human stellate cells treated with three concentrations of silibinin(10, 50 and 100 μmol/L) for 24 and 96 hours. At the end of the treatment cell viability and proliferation were evaluated. Protein expression of p27, p21, p53, Akt and phosphorylated-Akt was evaluated by Western blotting analysis and Ki-67 protein expression was by immunocytochemistry. Sirtuin activity was evaluated by chemiluminescence based assay. RESULTS: Silibinin inhibits LX-2 cell proliferation in doseand time-dependent manner; we showed that silibinin upregulated the protein expressions of p27 and p53. Such regulation was correlated to an inhibition of both downstream Akt and phosphorylated-Akt protein signaling and Ki-67 protein expression. Sirtuin activity also was correlated to silibinininhibited proliferation of LX-2 cells. CONCLUSION: The anti-proliferative effect of silibinin on LX-2 human stellate cells is via the inhibition of the expressions of various cell cycle targets including p27, Akt and sirtuin signaling.Devaraj Ezhilarasan Jonathan Evraerts Brice Sid Pedro Buc Calderon Sivanesan Karthikeyan Etienne Sokal Mustapha Najimi 2017Hepatobiliary & Pancreatic Diseases International2017,16,1:7
7Epithelial cells with hepatobiliary phenotype:Is it another stem cell candidate for healthy adult human liver?显示文摘AIM:To investigate the presence and role of liver epithelial cells in the healthy human adult liver.METHODS:Fifteen days after human hepatocyte primary culture,epithelial like cells emerged and started proliferating.Cell colonies were isolated and sub-cultured for more than 160 d under specific culture conditions.Cells were analyzed for each passage using immunofluorescence,flow cytometry and reverse transcription-polymerase chain reaction(RT-PCR).RESULTS:Flow cytometry analysis demonstrated that liver epithelial cells expressed common markers for hepatic and stem cells such as CD90,CD44 and CD29 but were negative for CD34 and CD117.Using immunofluorescence we demonstrated that liver epithelial cells expressed not only immature(α-fetoprotein)but also differentiated hepatocyte(albumin and CK-18)and biliary markers(CK-7 and 19),whereas they were negative for OV-6.RT-PCR analysis confirmed immunofluorescence data and revealed that liver epithelial cells did not express mature hepatocyte markers such as CYP2B6,CYP3A4 and tyrosine amino-transferase.Purified liver epithelial cells were transplanted into SCID mice.One month after transplantation,albumin positive cell foci were detected in the recipient mouse parenchyma.CONCLUSION:According to their immature and bipotential phenotype,liver epithelial cells might represent a pool of precursors in the healthy human adult liver other than oval cells.Dung Ngoc Khuu Mustapha Najimi Etienne M Sokal 2007World Journal of Gastroenterology2007,13,10:3
8Serum uric acid level in acute stroke patients显示文摘Mehrpour M Khuzan M Najimi N 2012Med J Islam Repub Iran2012,26,2:1
9Durability of Copper Slag Contained Concrete Exposed to Sulfate Attack显示文摘Najimi M Sobhani J Pourkhorshidi A R 2011Construction and Building Materials2011,25,4:1
10Molecular and functional eharacterisation of glutamate transporters in rat cortical astrocytes exposed to a defined combination of growth factors during in vitro differentiation显示文摘Vermeiren C Najimi M Maloteaux JM 2005Neurochem2005,46,2:1
11Properties of Concrete Containing Copper Slag Waste显示文摘Najimi Meysam Pourkhorshidi Ali Reza 2011Magazine of Concrete Research2011,63,60:1
12Robust control of speed and temperature in a power plant gas turbine 显示文摘NAJIMI E RAMEZANI M H 2012ISA Transactions2012,51,2:1
13Update on liver cell transplantation显示文摘Najimi M Sokal E 2004J Pediatric Gastroenterol Nutrition2004,39,4:1
14Serum uric acid level in a- cute stroke patients 显示文摘Mehrpour M Khuzan M Najimi N 2012Med J Islam Repub lran2012,26,2:1
15Acute up-regulation of glutamate uptake mediated by mGluRSa in reactive astrocytes 显示文摘ermeiren C Najimi M Vanhoutte N 2005J Neurochem2005,94,2:1
16Pertussis toxin-sensitive modulation of glutamate transport by endothelin-1 type A receptors in glioma cells显示文摘Mustapha Najimi Jean-Marie Maloteaux Emmanuel Hermans 2004BBA - Biomembranes2004,,2:1
17Job stress and its relationship with the level of secretory IgA in saliva:a comparison between nurses working in emergency wards and hospital clerks显示文摘Golshiri P Pourabdian S Najimi A 0,,3:1
18Serum uric acid level in acute stroke patients显示文摘Mehrpour M Khuzan M Najimi N 2012Med J Islam Repub Iran2012,26,2:1
19Job stress and its relationship with the level of secretory IgA in saliva: a comparison between nurses working in emergency wards and hospital clerks显示文摘Golshiri P Pourabdian S Najimi A 2012J Pak Med Assoc2012,62,32:1
20Liver celi transplantation显示文摘Najimi M Sokal E Minerva Pediatrica0,,:1
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