Objective:To investigate whether atractylenolide Ⅰ(ATL-Ⅰ) has protective effect on lipopolysaccharide(LPS)-induced disseminated intravascular coagulation(DIC) in vivo and in vitro,and explore whether NF-κB signalin...Objective:To investigate whether atractylenolide Ⅰ(ATL-Ⅰ) has protective effect on lipopolysaccharide(LPS)-induced disseminated intravascular coagulation(DIC) in vivo and in vitro,and explore whether NF-κB signaling pathway is involved in ATL-Ⅰ treatment.Methods:New Zealand white rabbits were injected with LPS through marginal ear vein over a period of 6h at a rate of 600 μg/kg(10 mL/h).Similarly,in the treatment groups,1.0,2.0,or 5.0 mg/kg ATL-Ⅰ were given.Both survival rate and organ function were tested,including the level of alanine aminotransferase(ALT),blood urine nitrogen(BUN),and TNF-α were examined by ELISA.Also haemostatic and fibrinolytic parameters in serum were measured.RAW 264.7 macrophage cells were administered with control,LPS,LPS + ATL-Ⅰ and ATL-Ⅰ alone,and TNF-α,phosphorylation(P)-IκBα,phosphorylation(P)-NF-κB(P65) and NF-κB(P65) were determined by Western blot.Results:The administration of LPS resulted in 73.3%mortality rate,and the increase of serum TNF-α,BUN and ALT levels.When ATL-Ⅰ treatment significantly increased the survival rate of LPS-induced DIC model,also improved the function of blood coagulation.And protein analysis indicated that ATL-Ⅰ remarkably protected liver and renal as decreasing TNF-α expression.In vitro,ATL-Ⅰ obviously decreased LPS-induced TNF-αproduction and the expression of P-NF-κB(P65),with the decrease of P-IκBα.Conclusions:ATL-Ⅰ has protective effect on LPS-induced DIC,which can elevate the survival rate,reduce organ damage,improve the function of blood coagulation and suppress TNF-α expression by inhibiting the activation of NF-κB signaling pathway.展开更多
Background The intestinal epithelium performs essential physiological functions,such as nutrient absorption,and acts as a barrier to prevent the entry of harmful substances.Mycotoxins are prevalent contaminants found ...Background The intestinal epithelium performs essential physiological functions,such as nutrient absorption,and acts as a barrier to prevent the entry of harmful substances.Mycotoxins are prevalent contaminants found in ani-mal feed that exert harmful effects on the health of livestock.Zearalenone(ZEA)is produced by the Fusarium genus and induces gastrointestinal dysfunction and disrupts the health and immune system of animals.Here,we evaluated the molecular mechanisms that regulate the effects of ZEA on the porcine intestinal epithelium.Results Treatment of IPEC-J2 cells with ZEA decreased the expression of E-cadherin and increased the expression of Snai1 and Vimentin,which induced Snail1-mediated epithelial-to-mesenchymal transition(EMT).In addition,ZEA induces Snail-mediated EMT through the activation of TGF-βsignaling.The treatment of IPEC-J2 cells with atractyle-nolideⅢ,which were exposed to ZEA,alleviated EMT.Conclusions Our findings provide insights into the molecular mechanisms of ZEA toxicity in porcine intestinal epi-thelial cells and ways to mitigate it.展开更多
基金funded by grants from the Science and Technology Planning Project of Guangdong Province(2014A020211022)Science and Technology Planning Project of Guangzhou Province(201510010074)
文摘Objective:To investigate whether atractylenolide Ⅰ(ATL-Ⅰ) has protective effect on lipopolysaccharide(LPS)-induced disseminated intravascular coagulation(DIC) in vivo and in vitro,and explore whether NF-κB signaling pathway is involved in ATL-Ⅰ treatment.Methods:New Zealand white rabbits were injected with LPS through marginal ear vein over a period of 6h at a rate of 600 μg/kg(10 mL/h).Similarly,in the treatment groups,1.0,2.0,or 5.0 mg/kg ATL-Ⅰ were given.Both survival rate and organ function were tested,including the level of alanine aminotransferase(ALT),blood urine nitrogen(BUN),and TNF-α were examined by ELISA.Also haemostatic and fibrinolytic parameters in serum were measured.RAW 264.7 macrophage cells were administered with control,LPS,LPS + ATL-Ⅰ and ATL-Ⅰ alone,and TNF-α,phosphorylation(P)-IκBα,phosphorylation(P)-NF-κB(P65) and NF-κB(P65) were determined by Western blot.Results:The administration of LPS resulted in 73.3%mortality rate,and the increase of serum TNF-α,BUN and ALT levels.When ATL-Ⅰ treatment significantly increased the survival rate of LPS-induced DIC model,also improved the function of blood coagulation.And protein analysis indicated that ATL-Ⅰ remarkably protected liver and renal as decreasing TNF-α expression.In vitro,ATL-Ⅰ obviously decreased LPS-induced TNF-αproduction and the expression of P-NF-κB(P65),with the decrease of P-IκBα.Conclusions:ATL-Ⅰ has protective effect on LPS-induced DIC,which can elevate the survival rate,reduce organ damage,improve the function of blood coagulation and suppress TNF-α expression by inhibiting the activation of NF-κB signaling pathway.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2022R1I1A3070740)。
文摘Background The intestinal epithelium performs essential physiological functions,such as nutrient absorption,and acts as a barrier to prevent the entry of harmful substances.Mycotoxins are prevalent contaminants found in ani-mal feed that exert harmful effects on the health of livestock.Zearalenone(ZEA)is produced by the Fusarium genus and induces gastrointestinal dysfunction and disrupts the health and immune system of animals.Here,we evaluated the molecular mechanisms that regulate the effects of ZEA on the porcine intestinal epithelium.Results Treatment of IPEC-J2 cells with ZEA decreased the expression of E-cadherin and increased the expression of Snai1 and Vimentin,which induced Snail1-mediated epithelial-to-mesenchymal transition(EMT).In addition,ZEA induces Snail-mediated EMT through the activation of TGF-βsignaling.The treatment of IPEC-J2 cells with atractyle-nolideⅢ,which were exposed to ZEA,alleviated EMT.Conclusions Our findings provide insights into the molecular mechanisms of ZEA toxicity in porcine intestinal epi-thelial cells and ways to mitigate it.
文摘工程结构在制造工艺过程中或使用期间会产生裂纹,对结构断裂路径的预测和研究是防治工程安全问题发生的重要手段。在考虑裂纹尖端应力场常数项T应力的基础上对传统的最大周向应力准则(Maximum tangential stress criterion,MTS)和最小应变能密度因子准则(Minimum strain energy density criterion,SED)进行修正,采用Python语言对ABAQUS的前、后处理和有限元计算模块进行二次开发,通过计算最优解的粒子群算法(Particle swarm optimization,PSO)将修正后的准则编入裂纹自动扩展程序脚本中。利用上述二次开发程序对初始纯Ⅰ型裂纹的扩展路径进行模拟,结果表明:采用ABAQUS脚本程序模拟结果与相关文献实验结果吻合,表明了程序的有效性,进而实现考虑T应力的多种断裂准则对裂纹扩展路径的预测;当T应力值处于一定范围内时,修正的MTS准则无法预测裂纹发生的偏转现象,扩展路径呈直线,此时可采用修正的SED准则进行预测。
