New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

C-reactive Protein Level,Apolipoprotein B-to-apolipoprotein A-1 Ratio,and Risks of Ischemic Stroke and Coronary Heart Disease among Inner Mongolians in China

Objective We aimed to investigate the cumulative effect of high CRP level and apolipoprotein B-to-apolipoprotein A-1（ApoB/ApoA-1） ratio on the incidence of ischemic stroke（IS） or coronary heart disease（CHD） in a Mongolian population in China.Methods From June 2003 to July 2012,2589 Mongolian participants were followed up for IS and CHD events based on baseline investigation.All the participants were divided into four subgroups according to C-reactive protein（CRP） level and ApoB/ApoA-1 ratio.Cox proportional hazard models were used to estimate the hazard ratios（HRs） and 95% confidence intervals（CIs） for the IS and CHD events in all the subgroups.Results The HRs（95% CI） for IS and CHD were 1.33（0.84-2.12）,1.14（0.69-1.88）,and 1.91（1.17-3.11） in the ‘low CRP level with high ApoB/ApoA-1＇,‘high CRP level with low ApoB/ApoA-1＇,and ‘high CRP level with high ApoB/ApoA-1＇ subgroups,respectively,in comparison with the ‘low CRP level with low ApoB/ApoA-1＇ subgroup.The risks of IS and CHD events was highest in the ‘high CRP level with high ApoB/ApoA-1＇ subgroup,with statistical significance.Conclusion High CRP level with high ApoB/ApoA-1 ratio was associated with the highest risks of IS and CHD in the Mongolian population.This study suggests that the combination of high CRP and ApoB/ApoA-1 ratio may improve the assessment of future risk of developing IS and CHD in the general population.

Autoantibodies to apolipoprotein A-1 as a biomarker of cardiovascular autoimmunity

Immune-driven inflammation plays an important part inatherogenesis and is therefore believed to be key to thedevelopment of cardiovascular disease(CVD), whichis currently the leading cause of death in the Westernworld. By fulfilling some of the Koch postulates, athero-genesis has even been proposed to be considered as anautoimmune disease, raising the hope that CVD couldbe prevented by immunomodulation. Nevertheless,the role of the immune system and autoimmune reac-tions in atherosclerosis appear to be a double edged-sword, with both pro-atherogenic and anti-atherogenicattributes. Hence, if immunomodulation is to becomea therapeutic option for atherosclerosis and CVD, it willbe crucial to correctly identify patients who might ben-efit from targeted suppression of deleterious autoim-mune responses. This could be achieved, for example, by the detection of disease-associated autoantibodies. In this work, we will review the currently available clini-cal, in vitro, and animal studies dedicated to autoan-tibodies against apolipoprotein A-1(anti-apoA-1 IgG), the major proteic fraction of high density lipoprotein. Current clinical studies indicate that high levels of anti-apoA-1 IgG are associated with a worse cardiovascular prognosis. In addition, in vitro and animal studies indi-cate a pro-inflammatory and pro-atherogenic role, sup-porting the hypothesis that these autoantibodies may play a direct causal role in CVD, and furthermore that they could potentially represent a therapeutic target for CVD in the future.

Apolipoprotein B100 quality control and the regulation of hepatic very low density lipoprotein secretion

Apolipoprotein B （apoB） is the main protein component of very low density lipoprotein （VLDL） and is necessary for the assembly and secretion of these triglyceride （TG）-rich particles. Following release from the liver, VLDL is converted to low density lipoprotein （LDL） in the plasma and increased production of VLDL can therefore play a detrimental role in cardiovascular disease. Increasing evidence has helped to establish VLDL assembly as a target for the treatment of dyslipidemias. Multiple factors are involved in the folding of the apoB protein and the formation of a secretion-competent VLDL particle. Failed VLDL assembly can initiate quality control mechanisms in the hepatocyte that target apoB for degradation. ApoB is a substrate for endoplasmic reticulum associated degradation （ERAD） by the ubiquitin proteasome system and for autophagy. Efficient targeting and disposal of apoB is a regu- lated process that modulates VLDL secretion and partitioning of TG. Emerging evidence suggests that significant overlap exists between these degradative pathways. For example, the insulin-mediated targeting of apoB to autop- hagy and postprandial activation of the unfolded protein response （UPR） may employ the same cellular machinery and regulatory cues. Changes in the quality control mechanisms for apoB impact hepatic physiology and pathology states, including insulin resistance and fatty liver. Insulin signaling, lipid metabolism and the hepatic UPR may impact VLDL production, particularly during the postprandial state. In this review we summarize our current understanding of VLDL assembly, apoB degradation, quality control mechanisms and the role of these processes in liver physiology and in pathologic states.

Apolipoprotein B/Apolipoprotein A1 ratio is associated with sex hormone binding globulin and may be an indicator of metabolic syndrome in PCOS women

Objective To identify significant factors related to the apolipoprotein B/apolipoprotein A1 （apoB/A1） ratio and investigate the association between the apoB/A1 ratio and metabolic syndrome （MS） in polycystic ovary syndrome （PCOS） women. Methods Totally 307 subjects with PCOS were collected and recruited fulfilling the revised 2003 Rotterdam diagnostic criteria. MS was diagnosed by the National Cholesterol Education Program-Adult treatment Panel （NCEP-ATP） III criteria. Results The prevalence of MS in PCOS women was 31.6%, whose average age was 26.2 ___＋ 5.2 years. The apoB/A1 ratio was significantly correlated with age, body mass index （BM1）, waist circumference （WC）, hip circumference, waist-to-hip ratio, blood pressure, metabolic abnormalities, sex hormone binding globulin （SHBG）, and free androgen index. In addition, SHBG had a significant association with all five component risk of MS. The increasing apoB/A1 ratio was associated with the prevalence of MS and was one of the risk factors of MS. Conclusion SHBG was considered as an additional potential factor in predicting the metabolic abnormity in PCOS women. The apoB/A1 ratio is associated with SHBG and might be an indicator of MS in PCOS women.

Apolipoprotein E2 inhibits mitochondrial apoptosis in pancreatic cancer cells through ERK1/2/CREB/BCL-2 signaling

Background: Apolipoprotein E2(ApoE2) is a pleiotropic protein that influences several aspects of cancer metabolism and development. Evading apoptosis is a vital factor for facilitating cancer cell growth. However, the role and mechanism of ApoE2 in regulating cell apoptosis of pancreatic cancer remain unclear. Methods: In this study, we firstly detected the m RNA and protein expressions of ApoE2 in PANC-1 and Capan-2 cells by real-time polymerase chain reaction and Western blotting. We then performed TUNEL and flow cytometric analyses to explore the role of recombinant human ApoE2, p CMV6-ApoE2 and si ApoE2 in the apoptosis of PANC-1 and Capan-2 cells. Furthermore, we investigated the molecular mechanism through which ApoE2 affected apoptosis in PANC-1 cells using immunofluorescence, immunoprecipitation, Western blotting and co-immunoprecipitation analysis. Results: ApoE2 phosphorylated ERK1/2 and inhibited pancreatic cancer cell apoptosis. In addition, our data showed that ApoE2/ERK1/2 altered the expression and mitochondrial localization of BCL-2 via activating CREB. ApoE2/ERK1/2/CREB also increased the total BCL-2/BAX ratio, inhibited the opening of the mitochondrial permeability transition pore and the depolarization of mitochondrial transmembrane potential, blocked the leakage of cytochrome-c and the formation of the apoptosome, and consequently, suppressed mitochondrial apoptosis. Conclusions: ApoE2 regulates the mitochondrial localization and expression of BCL-2 through the activation of the ERK1/2/CREB signaling cascade to evade the mitochondrial apoptosis of pancreatic cancer cells. ApoE2 may be a distinct prognostic marker and a potential therapeutic target for pancreatic cancer.

Role of apolipoproteins,ABCA1 and LCAT in the biogenesis of normal and aberrant high density lipoproteins

In this review, we focus on the pathway of biogenesis of HDL, the essential role of apoA-I, ATP binding cassette transporter A1（ABCA1）, and lecithin： cholesterol acyltransferase（LCAT） in the formation of plasma HDL; the generation of aberrant forms of HDL containing mutant apoA-I forms and the role of apoA-IV and apoE in the formation of distinct HDL subpopulations. The biogenesis of HDL requires functional interactions of the ABCA1 with apoA-I（and to a lesser extent with apoE and apoA-IV） and subsequent interactions of the nascent HDL species thus formed with LCAT. Mutations in apoA-I, ABCA1 and LCAT either prevent or impair the formation of HDL and may also affect the functionality of the HDL species formed. Emphasis is placed on three categories of apoA-I mutations. The first category describes a unique bio-engineered apoA-I mutation that disrupts interactions between apoA-I and ABCA1 and generates aberrant prep HDL subpopulations that cannot be converted efficiently to a subpopulations by LCAT. The second category describes natural and bio-engineered apoA-I mutations that generate preβ and small size a4 HDL subpopulations, and are associated with low plasma HDL levels. These phenotypes can be corrected by excess LCAT. The third category describes bio-engineered apoA-I mutations that induce hypertriglyceridemia that can be corrected by excess lipoprotein lipase and also have defective maturation of HDL.The HDL phenotypes described here may serve in the future for diagnosis, prognoses and potential treatment of abnormalities that affect the biogenesis and functionality of HDL.

Apolipoprotein A1 suppresses the hypoxia-induced angiogenesis of human retinal endothelial cells by targeting PlGF

AIM:To investigate the anti-angiogenic effect of apolipoprotein A1(apoA1)on primary human retinal vascular endothelial cells(HRECs)and explore the possible mechanism.METHODS:The primary HRECs were transfected with apoA1-GFP recombinant lentiviral and were compared with cells undergoing transfection with empty lentiviral vectors.Hypoxia chambers were used to simulate the anoxic environment of cells under pathological condition.The concentrations of secreted vascular endothelial growth factor(VEGF)and placental growth factor(PlGF)were measured by enzyme-linked immunosorbent assay(ELISA).Cell migration ability was detected by wound healing assay.The sprouting of HRECs was determined by tube formation assay.The protein levels of extracellular signal regulated kinase 1/2(ERK1/2)and phosphor ylated ERK1/2(p-ERK1/2)were measured by Western blot.RESULTS:Overexpressed apoA1 in hypoxia-induced HRECs significantly suppressed PlGF(0.67±0.10 folds,P=0.007).Overexpressed apoA1 also attenuated hypoxiainduced cell migration(0.32±0.11 folds,P<0.0001),tube formation(0.66±0.01 folds,P<0.0001)and the phosphorylation levels of ERK(0.6±0.11 folds,P=0.025).Pretreatment of mitogen-activated protein kinase kinase(MEK)inhibitor(U0126)further reduced the PlGF and angiogenesis in hypoxia-induced HRECs.CONCLUSION:ApoA 1 inhibits the angiogenesis at least in part by inactivating ERK1/2 in hypoxia-induced HRECs.Moreover,apoA1 suppresses the PlGF expression,which selectively associated with pathological angiogenesis.

Lp-PLA2 LP(a)ApoB/ApoA-1水平与急性脑梗死严重程度及预后的相关性分析

目的:探究脂蛋白相关磷脂酶A2(Lp-PLA2)、脂蛋白a[LP(a)]、载脂蛋白B(ApoB/)/载脂蛋白A-1(ApoA-1)的表达水平与急性脑梗死(ACI)的严重程度和预后的相关性。方法:选择我院2022年1月至2023年1月收治的ACI患者122例作为病例组,根据疾病严重程度分为轻度组(54例)、中度组(49例)、重度组(19例),另选择同期体检健康者作为对照组(97例)。根据预后效果分为预后良好组(88例)和预后不良组(34例)。比较病例组和对照组患者的基本资料和生化指标的差异性,分析Lp-PLA2、LP(a)、ApoB/ApoA-1的表达水平对患者病情严重程度和预后效果影响。结果:病例组患者年龄、吸烟史、高血压例数、收缩压、LDL-C、LP(a)、Lp-PLA2指标高于对照组(P<0.05),HDL-C指标低于对照组(P<0.05),多因素Logistic回归分析结果,年龄、吸烟史、高血压、收缩压、HDLC、LDLC、LPa、LpPLA2、ApoB/ApoA-1是影响ACI发生的独立危险因素(P<0.05)。重度组患者Lp-PLA2、LP(a)、ApoB/ApoA-1指标显著高于轻度组和中度组(P<0.05),中度组Lp-PLA2、LP(a)、ApoB/ApoA-1指标显著高于轻度组(P<0.05),Spearman相关性比较,Lp-PLA2、LP(a)、ApoB/ApoA-1指标与患者病情严重程度呈正相关(r=0.796、0.718、0.451,P<0.05)。预后良好组患者Lp-PLA2、LP(a)、ApoB/ApoA-1指标显著高于预后不良组(P<0.05),ROC曲线分析结果显示,联合预测AUC为0.987。结论:高龄、血压血脂异常、生活习惯较差者更易患ACI,而Lp-PLA2、ApoB/ApoA-1水平与ACI的严重程度和预后效果呈明显的相关性,通过检测可有效评估患者病情发展,具有较高临床价值。

老年糖尿病血清载脂蛋白A_1、载脂蛋白B测定分析

为探讨载脂蛋白A1（APOA1）、载脂蛋白B（APOB）与老年糖尿病关系及临床意义．测定54例老年糖尿病载脂蛋白APOA1、APOB．APOA1／APOB，总胆固醇（TC）．甘油三酯（TG）水平。结果：老年糖尿病及心脑并发症组与对照组比较．APOA1及APOA1／APOB无显著差异（p＞0．05）．而APOB．TC．TG显著升高（p＜0．05或P＜0.01）；老年糖尿病并心脑并发症组与单纯糖尿病组比较，APOA1，APOB.TC·TG·APOA1／APOB均无显著差异（p＞0．05）。提示．老年糖尿病存在广泛性脂代谢紊乱。

入院时血清淀粉酶、ApoB/ApoA1水平联合检测对重症急性胰腺炎的预测价值

目的:观察入院时血清淀粉酶、载脂蛋白B(ApoB)/载脂蛋白A1(ApoA1)水平联合检测对重症急性胰腺炎(AP)的预测价值。方法:回顾性分析2020年12月至2023年12月该院收治的86例AP患者的临床资料,按入院后是否发展为重症AP分为重症组(n=40)和非重症组(n=46),检测两组入院时血清淀粉酶、ApoB/ApoA1水平,并采用受试者工作特征(ROC)曲线,分析血清淀粉酶、ApoB/ApoA1水平单项及联合检测对重症AP的预测价值。结果:重症组入院时血清淀粉酶、ApoB/ApoA1水平均高于非重症组,差异有统计学意义(P<0.05);ROC曲线结果显示,入院时血清淀粉酶、ApoB/ApoA1水平联合检测预测重症AP的价值[曲线下面积(AUC)=0.821]高于二者单项预测(AUC=0.795、0.740)。结论:入院时血清淀粉酶、ApoB/ApoA1水平联合检测预测重症AP的价值高于二者单项预测。

载脂蛋白A_1和B免疫浊度法试剂盒的评价

对三种测定载脂蛋白A1和B（ApoA1，B）的免疫浊度测定试剂盒进行了评价，一种为德国Dia－Sys公司产品（D），另两种为国产试剂N和S。测定仪器为日立7150型自动分析仪．三种试剂在0．25～2．50g／L（APOA1和B）范围内均能得到符合要求的校准曲线．批内变异系数（％）分别为，APOA1：D1．39，N3．20，S2．17；ApoB：D2．30，N4．02，S3．93。测定结果ApoB三者相近；APOA1N偏高，S偏低，可能因定值血清标值不同所致。严重脂血测定ApoB时，D试剂不受影响，N和S均得到显著偏高的结果。30例临床标本用D和S对比测定，ApoA1r=0.912，ApoBr=0．864．ApoA1S的测定结果均较D略低，ApoBS有两例较高于D。

载脂蛋白A_1和B测定方法中标准曲线方式的评价

目的 :对载脂蛋白 ( Apolipoprotein,apo) A1和 B测定中的一点标准以及多点标准进行评价。方法 :以免疫透射比浊法 ( Immunoturbidimetry)中的一点法及二点法测定低、中、高值样品共 1 0 0例 ,比较采用不同方法标准曲线所得结果的差异。结果 :使用不同试剂及方法测定 ,单一试剂的一点法与二点法存在显著性差异 ;国产试剂用一点法一点定标 ,一点法多点非线性定标、二点法多点线性定标 ,均与进口试剂有统计学差异 ;而单一试剂二点法多点非线性定标结果与进口试剂的测定接近一致。结论 :多点标准优于一点标准 ;在单一试剂测定中 ,二点法好于一点法。

急性脑血管病患者血清高密度脂蛋白亚组分与ApoA_1,B含量变化的分析

检测急性脑血管病(ACVD)患者168例血清载脂蛋白(Apo)A_1,B,高密度脂蛋白胆固醇(HDLc)及其亚组分 HDL_(2c),血清总胆同醇(TC)和血清甘油三酯(TG)的含量,与相应年龄健康对照组比较,ACVD 患者血清 ApoA_1明显低于对照组(P<0.01),ApoB 则明显高于对照组(P<0.01),HDLc及其 HDL_(2c)均明显低于对照组(P<0.01和 P<0.001),TC 水平略有降低,与脑出血 TC 水平差异有显著意义(P<0.05),而脑梗塞组与脑出血组比较,ApoB,ApoB/ApoA_1比值有显著差异(P 均<0.01)。

脑梗死患者血清同型半胱氨酸 叶酸 铁蛋白APOB/APOA_1比值等的临床意义

目的探讨同型半胱氨酸(Hcy)、叶酸、超敏C反应蛋白(hs-CRP)、铁蛋白、甘油三酯(TG),总胆固醇(CHOL),高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、血清载脂蛋白B(APOB)/血清载脂蛋白A1(APOA1)比值与急性脑梗死的关系。方法选取2015年1月—2017年2月我院神经内科就诊的非脑血管疾病患者90例,2015年1月—2017年2月在我院神经内科住院120例急性脑梗死患者,检测2组患者血液Hcy、叶酸、hs-CRP、铁蛋白、TG、CHOL、HDL、LDL、APOB,APOA1,计算出APOB/APOA_1,并进行对比。结果脑梗死组患者Hcy、hs-CRP、铁蛋白、TG、LDL、APOB/APOA1水平较对照组高,叶酸较对照组低,差异均有统计学意义(P<0.05);2组CHOL、HDL水平比较差异无统计学意义(P>0.05)。结论血清同型半胱氨酸、叶酸、APOB/APOA1比值、脂蛋白等在急性脑梗死诊断、治疗和评估中具有重要意义。

ApoB/ApoA1比值、甘油三酯-葡萄糖指数与老年创伤性脑损伤严重程度和预后的关系

目的探讨载脂蛋白B(ApoB)/载脂蛋白A1(ApoA1)比值、甘油三酯-葡萄糖(TyG)指数与创伤性脑损伤(TBI)严重程度和预后的关系。方法选择2018年1月至2023年1月绵阳市中心医院收治的112例TBI病人(TBI组)和79例健康志愿者(对照组)。根据入院时格拉斯哥昏迷评分量表(GCS)评分将TBI病人分为中度组(64例)和重度组(48例),出院6个月后采用格拉斯哥预后量表(GOS)评估神经预后,并据此将TBI病人分为预后不良组(23例)和预后良好组(89例)。收集临床资料,计算ApoB/ApoA1比值和TyG指数,采用Pearson相关系数描述ApoB/ApoA1比值和TyG指数与胰岛素抵抗(HOMA-IR)、GCS评分的相关性,采用多因素Logistic回归分析影响TBI病人预后的因素,采用ROC曲线分析ApoB/ApoA1比值和TyG指数预测TBI病人预后的价值。结果TBI组ApoB/ApoA1比值、TyG指数、HOMA-IR显著高于对照组(P<0.05),且重度组高于中度组(P<0.05)。TBI病人ApoB/ApoA1比值、TyG指数与GCS评分呈负相关(P<0.05),与HOMA-IR呈正相关(P<0.05)。脑室出血、高ApoB/ApoA1比值、高TyG指数、高HOMA-IR是TBI病人预后不良的危险因素(P<0.05)。ApoB/ApoA1比值、TyG指数预测TBI病人预后的AUC分别为0.744、0.755,与HOMA-IR(0.794)接近(P>0.05),联合ApoB/ApoA1比值、TyG指数、HOMA-IR预测TBI病人预后的AUC为0.888,大于各指标单独预测价值(P<0.05)。结论TBI病人ApoB/ApoA1比值、TyG指数增高与神经损伤加重和预后不良有关,检测ApoB/ApoA1比值、TyG指数有助于评估TBI病人预后不良风险。

血清视黄醇结合蛋白、胱抑素C及载脂蛋白B/载脂蛋白A1联合检测对高血压早期肾损伤的诊断价值

目的:探讨视黄醇结合蛋白(RBP)、胱抑素C(Cys-C)及载脂蛋白B/载脂蛋白A1(ApoB/ApoA1)检测对高血压早期肾损伤的诊断价值。方法:选取80例高血压患者为研究对象,根据早期肾损伤诊断标准将其分为单纯高血压组(n=47)及高血压合并早期肾损伤组(n=33)。比较两组患者一般资料、血脂、RBP、Cys-C、ApoB/ApoA1水平,采用Logistic回归分析高血压患者早期肾损伤的危险因素。采用ROC曲线评估RBP、Cys-C、ApoB/ApoA1及其联合对高血压患者早期肾损伤的诊断效能。结果:早期肾损伤组患者RBP、Cys-C、ApoB/ApoA1水平均高于单纯高血压组,ApoA1水平低于单纯高血压组,差异均有统计学意义(P<0.05)。多因素Logistic回归分析显示,RBP、Cys-C、ApoB/ApoA1是原发性高血压患者合并早期肾损伤的危险因素(P<0.05)。ROC分析显示,当RBP≥3.475 mg/L时,诊断原发性高血压患者合并早期肾损伤的曲线下面积(AUC)为0.729,灵敏度为69.7%,特异度为72.3%;当Cys-C≥2.525 mg/L时,AUC为0.768,灵敏度为72.7%,特异度为74.5%;当ApoB/ApoA1≥0.870时,AUC为0.656,灵敏度为63.6%,特异度为68.1%;三者联合诊断的AUC为0.870,灵敏度为81.8%,特异度为80.9%。结论:高血压合并早期肾损伤患者RBP、Cys-C、ApoB/ApoA1水平升高,可将其联合用于高血压合并早期肾损伤的辅助诊断。

人参皂苷Rb1通过载脂蛋白M/线粒体凋亡途径对肝癌的影响及机制研究

目的:探究载脂蛋白M(ApoM)/线粒体凋亡在肝癌中的作用,以及人参皂苷Rb1(Rb1)通过ApoM/线粒体凋亡途径对肝癌影响的潜在机制。方法:生物信息学分析筛选ApoM在肝癌中的差异性表达及临床验证;分子对接技术确定Rb1与ApoM的靶向结合,体外培养人肝癌细胞(HepG2),并进行细胞活力检测(CCK-8)筛选Rb1最佳干预浓度,克隆实验用于检测HepG2细胞的增殖情况,划痕实验用于检测HepG2细胞的迁移能力,采用蛋白质印迹法(Western Blotting)检测ApoM及线粒体凋亡相关基因Bcl2相关X蛋白(Bax)、B淋巴细胞瘤-2(Bcl2)、胱天蛋白酶-3(Caspase-3)、胱天蛋白酶-9(Caspase-9)蛋白表达,实时萤光定量聚合酶链式反应(RT-qPCR)法检测ApoM及线粒体凋亡相关基因Bax、Bcl2、Caspase-3、Caspase-9 mRNA表达水平。结果:生存分析发现ApoM低表达肝癌预后更差,分子对接提示Rb1与ApoM之间具有较高亲和力,克隆及划痕实验提示Rb1有效抑制HepG2细胞增殖,Western Blotting及RT-qPCR验证Rb1可以干预线粒体凋亡相关基因蛋白和mRNA表达。结论:揭示了ApoM/线粒体凋亡在肝癌中发挥重要作用,人参皂苷Rb1可能通过ApoM/线粒体凋亡途径影响肝癌的可能潜在机制。

ApoA1、ApoB、ApoB/ApoA1比值、LDL-C/HDL-C比值及CHOL水平与ACS患者Gensini积分、冠状动脉易损斑块的关系分析

目的分析载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)、ApoB/ApoA1比值、低密度脂蛋白胆固醇/高密度脂蛋白胆固醇(LDL-C/HDL-C)比值及总胆固醇(CHOL)水平与急性冠脉综合征(ACS)患者Gensini积分、冠状动脉易损斑块的相关性。方法选取2022年3月至2023年10月该院收治的135例ACS患者为研究对象,其中不稳定型心绞痛患者(UAP组)70例,急性心肌梗死患者(AMI组)65例,均进行冠状动脉造影(CAG)和血管内超声(IVUS)检查,进行Gensini评分,依据CAG、IVUS结果将ACS患者分为稳定斑块组和易损斑块组,比较各组ApoA1、ApoB、ApoB/ApoA1比值、LDL-C/HDL-C比值及CHOL水平,分析ApoA1、ApoB、ApoB/ApoA1比值、LDL-C/HDL-C比值及CHOL水平与Gensini评分、冠状动脉易损斑块的相关性;采用受试者工作特征(ROC)曲线分析ApoA1、ApoB、ApoB/ApoA1比值、LDL-C/HDL-C比值及CHOL水平对冠状动脉易损斑块的预测价值。结果AMI组ApoB、ApoB/ApoA1比值、LDL-C/HDL-C比值、CHOL水平及Gensini评分均高于UAP组(P<0.05),ApoA1水平低于UAP组(P<0.05)。Pearson相关分析显示,Gensini评分与ApoB、ApoB/ApoA1比值、LDL-C/HDL-C比值、CHOL水平呈正相关(r=0.412、0.399、0.383、0.381,P<0.05),与ApoA1呈负相关(r=-0.405,P<0.05)。易损斑块组ApoB/ApoA1比值、LDL-C/HDL-C比值和CHOL水平均高于稳定斑块组(P<0.05),ApoA1水平低于稳定斑块组(P<0.05);两组ApoB水平比较,差异无统计学意义(P>0.05)。多因素Logistic回归分析显示,ApoA1水平降低及ApoB/ApoA1比值、LDL-C/HDL-C比值、CHOL水平升高均是ACS患者冠状动脉易损斑块的危险因素(P<0.05)。ROC曲线分析显示,ApoA1、ApoB/ApoA1比值、LDL-C/HDL-C比值、CHOL 4项联合预测ACS患者冠状动脉易损斑块的AUC为0.932(95%CI:0.875~0.968),均高于各指标单项预测ACS患者冠状动脉易损斑块的AUC(Z=3.279、3.108、3.117、3.344,P<0.05)。结论ApoA1、ApoB、ApoB/ApoA1比值、LDL-C/HDL-C比值及CHOL水平可评估ACS患者冠状动脉病变严重程度,ApoA1水平降低及ApoB/ApoA1比值、LDL-C/HDL-C比值、CHOL水平升高均是ACS患者易损斑块的危险因素,对冠状动脉易损斑块具有预测价值。

血栓弹力图参数联合ApoA1、ApoB水平对冠心病PCI术预后的预测价值

目的探讨血栓弹力图(TEG)参数联合血清载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)水平对冠心病择期经皮冠状动脉介入(PCI)术预后的预测方法。方法选取2020年1月—2023年6月于绵阳市中心医院接受PCI治疗的共106例患者,根据预后分为两组,其中预后不良组33例,预后良好组73例。回顾性收集分析患者资料,采用受试者工作特征(ROC)曲线评估TEG参数联合血清ApoA1、ApoB水平的预测价值。结果预后不良组凝血反应时间(R)值、凝固时间(K)值较预后良好组短,而Angel角(α)、图中两侧曲线的最宽距离(MA)值、血栓弹力图(ε)值高于预后良好组,最大凝固时间(m)值较预后良好组长(P<0.05);预后不良组ApoA1水平低于预后良好组,ApoB水平高于预后良好组(P<0.05);多因素Logistics回归分析显示,TEG参数中的R值、K值与血清ApoA1、ApoB均是患者PCI术预后的独立影响因素(P<0.05);ROC曲线分析结果显示,R值、K值、血清ApoA1及其ApoB联合预测的曲线下面积(AUC)分别为0.627、0.709、0.755、0.712、0.788,联合预测的AUC优于各单项指标,敏感度、特异度分别为100.00%、84.93%。结论TEG参数R值与K值、血清ApoA1、ApoB均是冠心病者PCI术预后的独立影响因素,其联合预测冠心病患者PCI术后预后不良时有较好的敏感度,在特异度上的优势也值得临床关注。