Objective There is a lack of effective and long-term safe drugs for the treatment of osteoarthritis(OA).Tetrandrine(Tet)has been approved and used to treat rheumatoid arthritis for several decades,but its effect on OA...Objective There is a lack of effective and long-term safe drugs for the treatment of osteoarthritis(OA).Tetrandrine(Tet)has been approved and used to treat rheumatoid arthritis for several decades,but its effect on OA has not been investigated.Herein,we explored the effect of Tet on OA and its underlying mechanism.Methods OA was induced using destabilization of the medial meniscus(DMM)in C57BL/6J mice.The animals were randomly divided into sham,DMM,Tet,celecoxib(CXB),and indomethacin(INDO)groups.Each group was given solvent or corresponding drugs by gavage for 7 weeks after convalescence.Pathological staining,OARSI scores,micro-computed tomography and behavior tests were performed to evaluate the effects of Tet.Results Tet remarkably alleviated cartilage injury in the knee joint,limited bone remodeling in the subchondral bone,and delayed progression of OA.Tet also significantly relieved joint pain and maintained function.Further mechanistic studies revealed that Tet lowered inflammatory cytokine levels and selectively suppressed gene and protein expression of cyclooxygenase(COX)-2 but not COX-1(P<0.01).Tet also reduced the production of prostaglandin E2 without damaging the gastric mucosa.Conclusion We found that Tet could selectively inhibit COX-2 gene expression and decrease cytokine levels in mice,thus reducing inflammation and improving OA without obvious gastric adverse events.These results provide a scientific basis for the clinical application of Tet in the treatment of OA.展开更多
The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly（lactic-co-glycolic acid）（PLGA） nanoparticles（TPNs） was studied. Stabilizer-free nanoprecipitation met...The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly（lactic-co-glycolic acid）（PLGA） nanoparticles（TPNs） was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles＇ surface with use of poly（styrene sulfonate） sodium salt（PSS） as anionic layer and poly（allylamine hydrochloride）（PAH） as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs（4 layers） exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of –57.8 m V. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles＇ surface could dramatically influence the drug release profile of TPNs（4 layers vs. 3 layers）. In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles＇ surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.展开更多
基金This study was supported by the Natural Science Foundation of Hubei Province(No.2020CFB868).
文摘Objective There is a lack of effective and long-term safe drugs for the treatment of osteoarthritis(OA).Tetrandrine(Tet)has been approved and used to treat rheumatoid arthritis for several decades,but its effect on OA has not been investigated.Herein,we explored the effect of Tet on OA and its underlying mechanism.Methods OA was induced using destabilization of the medial meniscus(DMM)in C57BL/6J mice.The animals were randomly divided into sham,DMM,Tet,celecoxib(CXB),and indomethacin(INDO)groups.Each group was given solvent or corresponding drugs by gavage for 7 weeks after convalescence.Pathological staining,OARSI scores,micro-computed tomography and behavior tests were performed to evaluate the effects of Tet.Results Tet remarkably alleviated cartilage injury in the knee joint,limited bone remodeling in the subchondral bone,and delayed progression of OA.Tet also significantly relieved joint pain and maintained function.Further mechanistic studies revealed that Tet lowered inflammatory cytokine levels and selectively suppressed gene and protein expression of cyclooxygenase(COX)-2 but not COX-1(P<0.01).Tet also reduced the production of prostaglandin E2 without damaging the gastric mucosa.Conclusion We found that Tet could selectively inhibit COX-2 gene expression and decrease cytokine levels in mice,thus reducing inflammation and improving OA without obvious gastric adverse events.These results provide a scientific basis for the clinical application of Tet in the treatment of OA.
文摘星基广播式自动相关监视(ADS-B,automatic dependent surveillance-broadcast)系统是一种新型的航空器监视技术,在未来空中交通管理系统中具有广阔的应用前景。为了深入研究星基ADS-B系统中航空器到卫星的空天链路通信性能,将专业软件Matlab和STK(system tool kit)有效联合,构建符合国际标准的星基ADS-B空天链路完整模型;通过离散事件动态交互模拟ADS-B消息的发送与接收全过程,最后统计得出体现星基ADS-B空天链路通信性能的消息识别概率(POI,possibility of identify)、消息检测概率(POD,possibility of detective)、信号接收功率、信号冲突概率、卫星覆盖范围等指标。仿真结果表明,随着区域内航空器数量上升,POI、POD下降,消息冲突概率上升。
基金supported by grants from the National Natural Science Foundation of China(No.81101690)Natural Science Foundation of Hubei Province(No.2014CFB403)Applied Basic Research Foundation of Wuhan Science and Technology Committee(No.2014060101010034)
文摘The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly（lactic-co-glycolic acid）（PLGA） nanoparticles（TPNs） was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles＇ surface with use of poly（styrene sulfonate） sodium salt（PSS） as anionic layer and poly（allylamine hydrochloride）（PAH） as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs（4 layers） exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of –57.8 m V. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles＇ surface could dramatically influence the drug release profile of TPNs（4 layers vs. 3 layers）. In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles＇ surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.
