Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis.It is still being explored in depth due to its complex molecular mechanisms of occurrence and development.Lipids play a crucial role in ...Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis.It is still being explored in depth due to its complex molecular mechanisms of occurrence and development.Lipids play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction processes,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tumors.More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment resistance.The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism.Therefore,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.展开更多
The in vitro inhibitory effects of chrysophanol and physcion on CYP1B1 were explored,utilizing ethoxyresorufin as the substrate.The inhibition kinetics of CYP1B1 by these compounds were assessed with escalating doses ...The in vitro inhibitory effects of chrysophanol and physcion on CYP1B1 were explored,utilizing ethoxyresorufin as the substrate.The inhibition kinetics of CYP1B1 by these compounds were assessed with escalating doses of ethoxyresorufin.Both chrysophanol(IC_(50)(0.47±0.01)μmol·L^(-1))and physcion(IC_(50)(0.35±0.02)μmol·L^(-1))significantly reduce the catalytic efficiency of CYP1B1.The V_(max)and K_(m)values are determined to be(51.9912±10.0547)pmol·μg^(-1)(protein)·min^(-1) and(0.9663±0.2987)nmol·L^(-1)for chrysophanol,and(45.4227±1.9978)pmol·μg^(-1)(protein)·min^(-1) and(0.4367±0.0386)nmol·L^(-1)for physcion,respectively.Kinetic analysis reveals that chrysophanol and physcion exert mixed inhibitory effects on CYP1B1.This mixed inhibition is primarily characterized by the compounds’ability to competitively bind to the active sites of CYP1B1,as well as potentially through non-competitive mechanisms,thereby reducing the enzyme’s catalytic efficiency.Molecular docking studies are conducted to elucidate the interaction between anthraquinone derivatives and CYP1B1,indicating that these compounds may inhibit CYP1B1 activity by binding to their active sites.The demonstrated capacity of chrysophanol and physcion to inhibit CYP1B1 enzymatic function unveils a potential anticancer mechanism,advancing our comprehension of how the structure of anthraquinone derivatives correlates with CYP1B1 inhibition and paving the way for developing innovative cancer treatments.展开更多
为氨甲环酸临床应用的拓宽和创新提供参考。检索中国知网、Web of Science、PubMed等数据库中近5年来与氨甲环酸非止血用途相关的文献,对氨甲环酸的功效、作用机制进行综述,并对其创新应用进行了讨论和展望。氨甲环酸由于其分子结构和...为氨甲环酸临床应用的拓宽和创新提供参考。检索中国知网、Web of Science、PubMed等数据库中近5年来与氨甲环酸非止血用途相关的文献,对氨甲环酸的功效、作用机制进行综述,并对其创新应用进行了讨论和展望。氨甲环酸由于其分子结构和抗纤溶作用,衍生出诸多功效,除了止血之外,还具有保护线粒体、抗菌、抗病毒、抗癌、延缓衰老、美白,治疗痤疮、玫瑰痤疮、黄褐斑、银屑病、炎症后色素沉着等功效。氨甲环酸在衰老、感染、癌症、皮肤等疾病的预防和治疗,以及医美项目中的应用具有巨大潜力,创新制剂和氨甲环酸衍生物的研发更有利于氨甲环酸功效的发挥。展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:22176195 and 82127801)National Key R&D Program of China(Grant No.:2022YFF0705003)+5 种基金the Shenzhen Key Laboratory of Precision Diagnosis and Treatment of Depression(Grant No.:ZDSYS20220606100606014)the Guangdong Province Zhu Jiang Talents Plan,China(Grant No.:2021QN02Y028)the Natural Science Foundation of Guangdong Province,China(Grant No.:2021A1515010171)the Key Program of Fundamental Research in Shenzhen,China(Grant No.:JCYJ20210324115811031)the Sustainable Development Program of Shenzhen,China(Grant No.:KCXFZ202002011008124)the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen(Grant Nos.:SZ2020ZD002 and SZ2020QN005).
文摘Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis.It is still being explored in depth due to its complex molecular mechanisms of occurrence and development.Lipids play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction processes,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tumors.More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment resistance.The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism.Therefore,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.
文摘目的探究罗氟普兰对噪声性耳鸣小鼠海马NOD样受体热蛋白结构域相关蛋白3(NLRP3)、胱天蛋白酶-1(caspase-1)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的影响。方法选取24只6~8周龄的无特定病原体雄性C57BL/6J小鼠,体重18~20 g,采用随机数字表法将其分为对照组、噪声暴露组、罗氟普兰干预组、罗氟普兰耳毒性检测组,各6只。其中噪声暴露组和罗氟普兰干预组通过100 d B宽带白噪声单次暴露2 h造模,罗氟普兰干预组、罗氟普兰耳毒性检测组连续注射7 d罗氟普兰[1 mg/(kg·d)],噪声暴露组、对照组连续注射7 d等量生理盐水。实验结束后,对四组进行听性脑干反应(ABR)、耳鸣行为学检测,对四组耳蜗基底膜进行荧光染色,采用实时荧光定量和蛋白质印迹法检测对照组、噪声暴露组、罗氟普兰干预组海马的NLRP3、caspase-1、IL-1β、TNF-α的mRNA及蛋白水平。结果干预后,四组ABR反应阈与干预前比较无明显变化。噪声暴露组间歇前抑制惊跳反射抑制率(GPIAS%)低于对照组,罗氟普兰干预组GPIAS%高于噪声暴露组(P<0.05)。罗氟普兰耳毒性检测组GPIAS%与对照组比较,差异无统计学意义(P>0.05)。四组耳蜗基底膜荧光染色显示四组内外毛细胞无明显异常。噪声暴露组NLRP3、caspase-1、IL-1β、TNF-αmRNA表达量及蛋白水平均高于对照组,罗氟普兰干预组低于噪声暴露组(P<0.05)。结论100 d B宽带白噪声可成功建立无明显听力损失的耳鸣小鼠模型,罗氟普兰无明显耳毒性,噪声暴露所致耳鸣可能与海马中炎症因子的表达量相关。
基金Supported by the Heilongjiang Administration of Traditional Chinese Medicine(ZHY2020-078)the Education Department of Heilongjiang Province(SJGY20210830)。
文摘The in vitro inhibitory effects of chrysophanol and physcion on CYP1B1 were explored,utilizing ethoxyresorufin as the substrate.The inhibition kinetics of CYP1B1 by these compounds were assessed with escalating doses of ethoxyresorufin.Both chrysophanol(IC_(50)(0.47±0.01)μmol·L^(-1))and physcion(IC_(50)(0.35±0.02)μmol·L^(-1))significantly reduce the catalytic efficiency of CYP1B1.The V_(max)and K_(m)values are determined to be(51.9912±10.0547)pmol·μg^(-1)(protein)·min^(-1) and(0.9663±0.2987)nmol·L^(-1)for chrysophanol,and(45.4227±1.9978)pmol·μg^(-1)(protein)·min^(-1) and(0.4367±0.0386)nmol·L^(-1)for physcion,respectively.Kinetic analysis reveals that chrysophanol and physcion exert mixed inhibitory effects on CYP1B1.This mixed inhibition is primarily characterized by the compounds’ability to competitively bind to the active sites of CYP1B1,as well as potentially through non-competitive mechanisms,thereby reducing the enzyme’s catalytic efficiency.Molecular docking studies are conducted to elucidate the interaction between anthraquinone derivatives and CYP1B1,indicating that these compounds may inhibit CYP1B1 activity by binding to their active sites.The demonstrated capacity of chrysophanol and physcion to inhibit CYP1B1 enzymatic function unveils a potential anticancer mechanism,advancing our comprehension of how the structure of anthraquinone derivatives correlates with CYP1B1 inhibition and paving the way for developing innovative cancer treatments.
文摘为氨甲环酸临床应用的拓宽和创新提供参考。检索中国知网、Web of Science、PubMed等数据库中近5年来与氨甲环酸非止血用途相关的文献,对氨甲环酸的功效、作用机制进行综述,并对其创新应用进行了讨论和展望。氨甲环酸由于其分子结构和抗纤溶作用,衍生出诸多功效,除了止血之外,还具有保护线粒体、抗菌、抗病毒、抗癌、延缓衰老、美白,治疗痤疮、玫瑰痤疮、黄褐斑、银屑病、炎症后色素沉着等功效。氨甲环酸在衰老、感染、癌症、皮肤等疾病的预防和治疗,以及医美项目中的应用具有巨大潜力,创新制剂和氨甲环酸衍生物的研发更有利于氨甲环酸功效的发挥。
