Proprotein convertase subtilisin/kexin type 9(PCSK9)has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases(CVD).This...Proprotein convertase subtilisin/kexin type 9(PCSK9)has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases(CVD).This comprehensive review delineates the intricate roles and wide-ranging implications of PCSK9,extending beyond CVD to emphasize its significance in diverse physiological and pathological states,including liver diseases,infectious diseases,autoimmune disorders,and notably,cancer.Our exploration offers insights into the interaction between PCSK9 and low-density lipoprotein receptors(LDLRs),elucidating its substantial impact on cholesterol homeostasis and cardiovascular health.It also details the evolution of PCSK9-targeted therapies,translating foundational bench discoveries into bedside applications for optimized patient care.The advent and clinical approval of innovative PCSK9 inhibitory therapies(PCSK9-iTs),including three monoclonal antibodies(Evolocumab,Alirocumab,and Tafolecimab)and one small interfering RNA(siRNA,Inclisiran),have marked a significant breakthrough in cardiovascular medicine.These therapies have demonstrated unparalleled efficacy in mitigating hypercholesterolemia,reducing cardiovascular risks,and have showcased profound value in clinical applications,offering novel therapeutic avenues and a promising future in personalized medicine for cardiovascular disorders.Furthermore,emerging research,inclusive of our findings,unveils PCSK9’s potential role as a pivotal indicator for cancer prognosis and its prospective application as a transformative target for cancer treatment.This review also highlights PCSK9’s aberrant expression in various cancer forms,its association with cancer prognosis,and its crucial roles in carcinogenesis and cancer immunity.In conclusion,this synthesized review integrates existing knowledge and novel insights on PCSK9,providing a holistic perspective on its transformative impact in reshaping therapeutic paradigms across various disorders.It emphasizes the clinical value and effect of PCSK9-iT,underscoring its potential in advancing the landscape of biomedical research and its capabilities in heralding new eras in personalized medicine.展开更多
Objective:To isolate,identify,and evaluate a new angiotensin-converting enzyme inhibitor from Peperomia pellucida(L.)Kunth herbs.Methods:A dried sample of Peperomia pellucida herb was successively macerated with n-hex...Objective:To isolate,identify,and evaluate a new angiotensin-converting enzyme inhibitor from Peperomia pellucida(L.)Kunth herbs.Methods:A dried sample of Peperomia pellucida herb was successively macerated with n-hexane and ethyl acetate.The ethyl acetate extract solution was evaporated to obtain the crude extract.Vacuum liquid column chromatography and thin layer chromatography were performed to obtain two pure compounds.Then,both compounds were elucidated and identified using the spectroscopic method.Angiotensin-converting enzyme inhibitory activity studies of both compounds were determined using angiotensin-converting enzyme kit WST-1 with spectrophotometer microplate reader 96-well at 450 nm wavelength.Results:Two bioactive compounds were successfully isolated from Peperomia pellucida herb,including a new compound of 2,3,5-trimethoxy-9-(12,14,15-trimethoxybenzyl)-1 H-indene and pellucidin A.Both compounds demonstrated angiotensin-converting enzyme inhibitory activity,with IC50 values of 72 μM(27.95 μg/mL)and 1 1μM(4.4 μg/mL),respectively.Conclusions:In the present study,two active angiotensin-converting enzyme inhibitors were successfully isolated and purified from Peperomia pellucida which is used as an antihypertensive in traditional medicine,and support its use as an angiotensin-converting enzyme-inhibiting drug.展开更多
基金supported by the National Natural Science Foundation of China(No.82272817,to X.B.)Shanghai Pujiang Program(No.22PJ1412400,to X.B.,and No.22PJ1402700,to Y.H.)Science and Technology Development Fund of Shanghai Pudong New Area(No.PKJ2022-Y50,to X.B.).
文摘Proprotein convertase subtilisin/kexin type 9(PCSK9)has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases(CVD).This comprehensive review delineates the intricate roles and wide-ranging implications of PCSK9,extending beyond CVD to emphasize its significance in diverse physiological and pathological states,including liver diseases,infectious diseases,autoimmune disorders,and notably,cancer.Our exploration offers insights into the interaction between PCSK9 and low-density lipoprotein receptors(LDLRs),elucidating its substantial impact on cholesterol homeostasis and cardiovascular health.It also details the evolution of PCSK9-targeted therapies,translating foundational bench discoveries into bedside applications for optimized patient care.The advent and clinical approval of innovative PCSK9 inhibitory therapies(PCSK9-iTs),including three monoclonal antibodies(Evolocumab,Alirocumab,and Tafolecimab)and one small interfering RNA(siRNA,Inclisiran),have marked a significant breakthrough in cardiovascular medicine.These therapies have demonstrated unparalleled efficacy in mitigating hypercholesterolemia,reducing cardiovascular risks,and have showcased profound value in clinical applications,offering novel therapeutic avenues and a promising future in personalized medicine for cardiovascular disorders.Furthermore,emerging research,inclusive of our findings,unveils PCSK9’s potential role as a pivotal indicator for cancer prognosis and its prospective application as a transformative target for cancer treatment.This review also highlights PCSK9’s aberrant expression in various cancer forms,its association with cancer prognosis,and its crucial roles in carcinogenesis and cancer immunity.In conclusion,this synthesized review integrates existing knowledge and novel insights on PCSK9,providing a holistic perspective on its transformative impact in reshaping therapeutic paradigms across various disorders.It emphasizes the clinical value and effect of PCSK9-iT,underscoring its potential in advancing the landscape of biomedical research and its capabilities in heralding new eras in personalized medicine.
文摘目的探讨急性心肌梗死(acute myocardial infarction,AMI)患者血浆前蛋白转化枯草杆菌蛋白酶9(PCSK9)水平对临床不良事件发生的预测价值。方法选取2017年1月~2018年12月在延安大学附属医院确诊的急性心肌梗死患者271例,平均年龄55.1±9.9岁,其中男性172例(63.47%),按出院后第1月、3月、6月、12月进行随访,随访1年,主要随访方式为电话随访和门诊随访,记录临床不良事件。共59例发生临床不良事件(21.77%)。ROC曲线结果显示:血浆PCSK9诊断AMI患者临床不良事件的最佳预测值为309.6ng/ml(曲线下面积、敏感度和特异度分别为0.773,0.779和0.746),据此将研究对象分为PCSK9(L)组(PCSK<309.6ng/ml),共163例,平均年龄55.1±9.4岁,男性102例;PCSK9(H)组(PCSK≥309.6ng/ml),共108例,平均年龄54.9±10.6岁,男性70例。比较PCSK9(H)组和PCSK9(L)组患者实验室指标血浆PCSK9、血清总胆固醇(TCHO)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血糖(GLU)、年龄、性别、既往史(吸烟、饮酒、糖尿病、高血压、高脂血症、冠心病)、入院时Killip心功能分级、左心射血分数及临床不良事件发生率。Cox回归分析血浆PCSK9水平对AMI患者临床不良事件的预测价值。结果PCSK9(H)组和PCSK9(L)组血浆PCSK9水平为386±70.31ng/ml vs 232±53.17ng/ml,差异有统计学意义(t=24.545,P=0.000),血清LDL-C水平为2.71±0.62mmol/L vs 2.19±0.57mmol/L,差异有统计学意义(t=3.616,P=0.037)。PCSK9(H)组和PCSK9(L)组复合心血管不良事件发生率为23.15%vs 11.66%,差异有统计学意义(χ^2=6.308,P=0.012),心力衰竭发生率为13.89%vs 5.52%,差异有统计学意义(χ^2=5.634,P=0.018)。经Log Rank检验:PCSK9(H)组和PCSK9(L)组非复合心血管事件生存率组间差异有统计学意义(χ^2=12.735,P=0.007)。经多因素Cox回归分析,血浆PCSK9水平是AMI患者复合心血管不良事件及心力衰竭的独立危险因素(HR=1.507~1.517,95%CI:1.218~1.735,均P<0.05)。结论血浆PCSK9水平是AMI患者临床不良心血管事件的独立危险因素。
基金supported by grant “Hibah Tugas Akhir Mahasiswa Doktor(TADOK)Tahun 2018” Directorate of Research and Humanity Engagement Universitas Indonesia(grant number:1234/UN2.R3.1/HKP.05.00/2018)
文摘Objective:To isolate,identify,and evaluate a new angiotensin-converting enzyme inhibitor from Peperomia pellucida(L.)Kunth herbs.Methods:A dried sample of Peperomia pellucida herb was successively macerated with n-hexane and ethyl acetate.The ethyl acetate extract solution was evaporated to obtain the crude extract.Vacuum liquid column chromatography and thin layer chromatography were performed to obtain two pure compounds.Then,both compounds were elucidated and identified using the spectroscopic method.Angiotensin-converting enzyme inhibitory activity studies of both compounds were determined using angiotensin-converting enzyme kit WST-1 with spectrophotometer microplate reader 96-well at 450 nm wavelength.Results:Two bioactive compounds were successfully isolated from Peperomia pellucida herb,including a new compound of 2,3,5-trimethoxy-9-(12,14,15-trimethoxybenzyl)-1 H-indene and pellucidin A.Both compounds demonstrated angiotensin-converting enzyme inhibitory activity,with IC50 values of 72 μM(27.95 μg/mL)and 1 1μM(4.4 μg/mL),respectively.Conclusions:In the present study,two active angiotensin-converting enzyme inhibitors were successfully isolated and purified from Peperomia pellucida which is used as an antihypertensive in traditional medicine,and support its use as an angiotensin-converting enzyme-inhibiting drug.
