地方性氟中毒的特征性病变过程即为骨组织的骨转换加速，亦称为高骨转换状态（high bone turnover state），主要表现为骨软化、骨硬化、骨质疏松和异位骨化。通过其病理演进特征，推测在其病变发生发展过程中应该存在着成骨过程的异常...地方性氟中毒的特征性病变过程即为骨组织的骨转换加速，亦称为高骨转换状态（high bone turnover state），主要表现为骨软化、骨硬化、骨质疏松和异位骨化。通过其病理演进特征，推测在其病变发生发展过程中应该存在着成骨过程的异常、破骨活性的改变和基质结构的变化并存的现象，即成骨过程和破骨过程这一矛盾的平衡被打破，从而倾向于建立新平衡过程的趋势发展，导致病变的产生。那么，氟进入体内究竟通过什么机制打破了这一平衡呢，这一问题引起了我们的兴趣。展开更多
Increasing numbers of clinical and experimental studies have proved that proteinuria plays a key role in the progression of chronic renal disease.In recent years,some molecular mechanisms of how proteinuria causes fur...Increasing numbers of clinical and experimental studies have proved that proteinuria plays a key role in the progression of chronic renal disease.In recent years,some molecular mechanisms of how proteinuria causes further kidney injuries have been revealed by many researches,although there are still many questions to be answered.Proteinuria triggers chemokine expression of tubular epithelial cells and activates complements,which result in interstitial inflammation and fibrosis;proteinuria also induces the apoptosis of tubular epithelial cells.Albumin in urine is considered as the main culprit,but other elements in proteinuria have also been suspected to cause renal damage,too.On the other hand,serum proteins leaking from glomerular barrier also adversely affect podocytes.Ultrafiltered serum proteins induce morphological changes and functional impairment of podocytes,resulting in exacerbating proteinuria;furthermore,TGF-β1 up-regulated by podocytes in response to protein overload contributes to the sclerosis of glomeruli.Studies on the mechanism of how proteinuria accelerates kidney diseases are important because they may offer novel therapeutic targets for controlling chronic kidney disease.For example,targeting directly on the complement synthesis and activation in proximal tubules,or chemokine production in tubular cells might be beneficial for preventing the progression of chronic proteinuric kidney disease to end stage renal disease.展开更多
文摘地方性氟中毒的特征性病变过程即为骨组织的骨转换加速，亦称为高骨转换状态（high bone turnover state），主要表现为骨软化、骨硬化、骨质疏松和异位骨化。通过其病理演进特征，推测在其病变发生发展过程中应该存在着成骨过程的异常、破骨活性的改变和基质结构的变化并存的现象，即成骨过程和破骨过程这一矛盾的平衡被打破，从而倾向于建立新平衡过程的趋势发展，导致病变的产生。那么，氟进入体内究竟通过什么机制打破了这一平衡呢，这一问题引起了我们的兴趣。
文摘Increasing numbers of clinical and experimental studies have proved that proteinuria plays a key role in the progression of chronic renal disease.In recent years,some molecular mechanisms of how proteinuria causes further kidney injuries have been revealed by many researches,although there are still many questions to be answered.Proteinuria triggers chemokine expression of tubular epithelial cells and activates complements,which result in interstitial inflammation and fibrosis;proteinuria also induces the apoptosis of tubular epithelial cells.Albumin in urine is considered as the main culprit,but other elements in proteinuria have also been suspected to cause renal damage,too.On the other hand,serum proteins leaking from glomerular barrier also adversely affect podocytes.Ultrafiltered serum proteins induce morphological changes and functional impairment of podocytes,resulting in exacerbating proteinuria;furthermore,TGF-β1 up-regulated by podocytes in response to protein overload contributes to the sclerosis of glomeruli.Studies on the mechanism of how proteinuria accelerates kidney diseases are important because they may offer novel therapeutic targets for controlling chronic kidney disease.For example,targeting directly on the complement synthesis and activation in proximal tubules,or chemokine production in tubular cells might be beneficial for preventing the progression of chronic proteinuric kidney disease to end stage renal disease.
文摘通过网络药理学和分子对接方法探讨鸡血藤治疗非小细胞肺癌的分子机制研究。以中药鸡血藤Spatholobi Caulis为对象,通过在中药药理学系统分析平台(TCMSP)数据库中获得鸡血藤中活性成分和相应潜在的药物靶点,利用GeneCards数据库收集癌症相关基因,借助Cytoscape软件构建鸡血藤活性成分-作用靶点-通路相互关系网络。应用DAVID数据库对靶点进行GO(gene ontology)及KEGG(Kyoto encyclopedia of genes and genomes)富集分析,并对KEGG信号通路进行可视化处理,将筛选出的化合物进行分子对接;最后,通过木犀草素、甘草查尔酮A处理人肺癌细胞A549进行核心靶点和通路的初步验证,运用CCK-8(cell counting kit-8)法检测细胞增殖,运用Western blot法检测caspase-3和Bax蛋白的表达。从中药鸡血藤中筛选出23个活性成分,潜在药物靶点170个,共涉及127条通路。分子对接结果表明,甘草查尔酮A、(Z)-3-(4-羟基-3-甲氧基苯基)-N-[2-(4-羟基苯基)乙基]丙烯酰胺、consume close grain与关键靶点EGFR成功对接,3个化合物的结合能小于-5 kcal·mol^(-1)。CCK-8法检测结果表明,木犀草素、甘草查尔酮A、鸡血藤提取物对人肺癌A549细胞有抑制作用。Western blot结果表明木犀草素、甘草查尔酮A、鸡血藤提取物能通过提高促凋亡因子caspase-3和Bax的表达,诱导细胞凋亡。该研究通过网络药理学与分子对接来研究鸡血藤抗肺癌作用,为后续鸡血藤治疗肺癌分子机制提供思路。
