Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish a...Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis.Methods:We simulated knee replacement in 16 male Sprague–Dawley rats.We immobilized the surgical leg with a suture in full flexion.The control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of arthrofibrosis.Immunofluorescent staining andα2-macroglobulin(α2M)enzyme-linked immunosorbent assay(ELISA)were used to assess local and systemic inflammation.Static weight bearing(total internal reflection)and range of motion(ROM)were collected for functional assessment.Results:The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups.Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue.Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels.The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group.Conclusions:This model is viable for simulating arthrofibrosis after joint replacement.Vitamin E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.展开更多
Previously, we reported that Y_6, a new epigallocatechin gallate derivative, is efficacious in reversing doxorubicin(DOX)–mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells. In this study, we evaluate...Previously, we reported that Y_6, a new epigallocatechin gallate derivative, is efficacious in reversing doxorubicin(DOX)–mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells. In this study, we evaluated the efficacy of Y_6 in reversing drug resistance both in vitro and in vivo by determining its effect on the adenosine triphosphate-binding cassette protein B1 transporter(ABCB1 or P-glycoprotein, P-gp). Our results showed that Y_6 significantly sensitized cells overexpressing the ABCB1 transporter to anticancer drugs that are ABCB1 substrates. Y_6 significantly stimulated the adenosine triphosphatase activity of ABCB1. Furthermore, Y_6 exhibited a higher docking score as compared with epigallocatechin gallate inside the transmembrane domain of ABCB1. In addition, in the nude mousetumor xenograft model, Y_6(110 mg/kg, intragastric administration), in combination with doxorubicin(2 mg/kg, intraperitoneal injection), significantly inhibited the growth of BEL-7404/DOX cell xenograft tumors, compared to equivalent epigallocatechin gallate. In conclusion, Y_6 significantly reversed ABCB1-mediated multidrug resistance and its mechanisms of action may result from its competitive inhibition of the ABCB1 drug efflux function.展开更多
基金supported in part by the Ruth Jackson Orthopedic Society and the Harris Orthopedic Laboratoryapproved by the Institutional Care and Use Committee of Massachusetts General Hospital(2020N000081)。
文摘Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues.Vitamin E is an antioxidant with potential anti-fibroblastic effect.The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis.Methods:We simulated knee replacement in 16 male Sprague–Dawley rats.We immobilized the surgical leg with a suture in full flexion.The control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of arthrofibrosis.Immunofluorescent staining andα2-macroglobulin(α2M)enzyme-linked immunosorbent assay(ELISA)were used to assess local and systemic inflammation.Static weight bearing(total internal reflection)and range of motion(ROM)were collected for functional assessment.Results:The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups.Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue.Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels.The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group.Conclusions:This model is viable for simulating arthrofibrosis after joint replacement.Vitamin E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.
基金supported by the National Natural Science Foundation of China (No. 81160532)the Open Project of Guangxi Colleges and Universities Key Laboratory of Biological Molecular Medicine Research (No. GXBMR201602, China)+1 种基金the Young and Middle-aged Teachers Foundation Ability Enhancement Project of Guangxi Colleges and Universities (No. 2018KY0102, China)US NIH (No. 1R15CA143701)
文摘Previously, we reported that Y_6, a new epigallocatechin gallate derivative, is efficacious in reversing doxorubicin(DOX)–mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells. In this study, we evaluated the efficacy of Y_6 in reversing drug resistance both in vitro and in vivo by determining its effect on the adenosine triphosphate-binding cassette protein B1 transporter(ABCB1 or P-glycoprotein, P-gp). Our results showed that Y_6 significantly sensitized cells overexpressing the ABCB1 transporter to anticancer drugs that are ABCB1 substrates. Y_6 significantly stimulated the adenosine triphosphatase activity of ABCB1. Furthermore, Y_6 exhibited a higher docking score as compared with epigallocatechin gallate inside the transmembrane domain of ABCB1. In addition, in the nude mousetumor xenograft model, Y_6(110 mg/kg, intragastric administration), in combination with doxorubicin(2 mg/kg, intraperitoneal injection), significantly inhibited the growth of BEL-7404/DOX cell xenograft tumors, compared to equivalent epigallocatechin gallate. In conclusion, Y_6 significantly reversed ABCB1-mediated multidrug resistance and its mechanisms of action may result from its competitive inhibition of the ABCB1 drug efflux function.
