作者: Voelkl, Jakob ; Makridakis, Manousos ; Lang, Florian ; Pieske, Burkert ; Schelski, Nadeshda ; Luong, Trang T D ; Vlahou, Antonia ; Alesutan, Ioana ; Boehme, Beate

Background/Aims: Fibulin-3, an extracellular matrix glycoprotein, inhibits vascular oxidative stress and remodeling in hypertension. Oxidative stress is prevalent in chronic kidney disease (CKD) patients and is an important mediator of osteo-/chondrogenic transdifferentiation and calcification of vascular smooth muscle cells (VSMCs) during hyperphosphatemia. Therefore, the present study explored the effects of Fibulin-3 on phosphate-induced vascular calcification. Methods: Experiments were performed in primary human aortic smooth muscle cells (HAoSMCs) treated with control or with phosphate without or with additional treatment with recombinant human Fibulin-3 protein or with hydrogen peroxide as an exogenous source of oxidative stress. Results: Treatment with calcification medium significantly increased calcium deposition in HAoSMCs, an effect significantly blunted by additional treatment with Fibulin-3. Moreover, phosphate-induced alkaline phosphatase activity and mRNA expression of osteogenic and chondrogenic markers MSX2, CBFA1, SOX9 and ALPL were all significantly reduced by addition of Fibulin-3. These effects were paralleled by similar regulation of oxidative stress in HAoSMCs. Phosphate treatment significantly up-regulated mRNA expression of the oxidative stress markers NOX4 and CYBA, down-regulated total antioxidant capacity and increased the expression of downstream effectors of oxidative stress PAI-1, MMP2 and MMP9 as well as BAX/BLC2 ratio in HAoSMCs, all effects blocked by additional treatment with Fibulin-3. Furthermore, the protective effects of Fibulin-3 on phosphate-induced osteogenic and chondrogenic markers expression in HAoSMCs were reversed by additional treatment with hydrogen peroxide. Conclusions: Fibulin-3 attenuates phosphate-induced osteo-/ chondrogenic transdifferentiation and calcification of VSMCs, effects involving inhibition of oxidative stress. Up-regulation or supplementation of Fibulin-3 may be beneficial in reducing the progression of vascular calcification during hyperphosphatemic conditions such as CKD.

2011-09-01·European Journal of Dermatology4区 · 医学

Treatment of psoriasis with recombinant human LFA3-antibody fusion protein: a multi-center, randomized, double-blind trial in a Chinese population

4区 · 医学

Article

作者: Guo, Zhi-Li ; Hao, Fei ; Tang, Min ; Gao, Tian-Wen ; Gao, Chun-Fang ; Li, Jing ; Yu, Jian-Bin ; Guo, Zai-Pei ; Li, Zhi ; Guo, Ya-Jun ; He, Wei ; Wang, Gang ; Gu, Jun ; Zhang, Jiang-An ; Li, Xian-Ping ; Li, Xiao-Hong ; Chen, Hao ; You, Yi ; Sun, Jian-Fang ; Yan, Heng ; Xiong, Lin ; Jiang, Yi-Qun

To evaluate clinical efficacy and safety of injectable recombinant human LFA3-antibody fusion protein (rhLFA3-IgFP), a multi-center, randomized, double-blind, double-dummy, parallel-controlled clinical trial was performed in 212 cases of moderate to severe psoriasis. Intramuscular injection of rhLFA3-IgFP (15 mg/week) and oral administration of blank dummy methotrexate at the dose of 7.5 mg/week was performed in the patients in the experimental group, and control patients were orally administered with methotrexate at the dose of 7.5 mg/week and intramuscularly injected with the blank dummy rhLFA3-IgFP (15 mg/week). PASI was determined prior to and at 2, 4, 6, 8, 12, 16, 20 weeks after the treatment. The efficacy evaluation was carried out on 192 patients, and no significant differences were found in PASI50, PASI75 & PASI90 between the two groups after twelve weeks' treatment (p>0.05). After discontinuation, PASI scores continued to decrease drastically in the experiment group, whereas they increased in the control group. At 8 weeks after discontinuation, PASI scores were decreased by 62.32% (p<0.05) and 52.67% (p<0.05) in the experimental and control groups, respectively. No serious adverse reactions were observed. In conclusion, the results of our investigation demonstrated that rhLFA3-IgFP was an effective therapy for chronic plaque psoriasis with lasting action and low incidence of adverse reactions.

2009-11-01·Current Opinion in Hematology3区 · 医学

Acute graft-versus-host disease: new treatment strategies

3区 · 医学

Review

作者: Sung W. Choi ; James L M Ferrara ; Sophie Paczesny

PURPOSE OF REVIEWGraft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), despite improvements in our understanding of its pathophysiology as well as the generation of new monoclonal antibodies, immunomodulatory chemotherapy, cellular therapeutics and supportive care. Herein, we review therapies that have proven effective as well as newer agents that have recently improved GVHD response rates and survival following HCT.RECENT FINDINGSNovel approaches to prevent or treat GVHD are often based on evidence from experimental models. Our understanding of the pathophysiology of GVHD may lead to the development of innovative strategies that target both soluble and cellular effectors. Among such agents are sirolimus, anti-tumor necrosis factor antibodies, anti-LFA-3-IgG fusion protein, extracorporeal photopheresis, mesenchymal stem cells and regulatory T cells.SUMMARYObstacles to the improvement of HCT include the tight linkage between GVHD toxicity and the beneficial graft-versus-leukemia (GVL) effect, as well as the impairment of immune reconstitution by immunomodulatory drugs leading to life-threatening infections. The design of newer phase I/II clinical trials are underway. Future therapies are likely to include modulation of cell types that play key roles in the GVH process, including regulatory T cells, dendritic cells, natural killer T cells and B cells.

100 项与 Recombinant human LFA-3-antibody fusion protein(Taizhou Mabtech Pharmaceutical Co. Ltd.) 相关的药物交易

登录后查看更多信息