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Association Between the Copper-to-Zinc Ratio and Cardiovascular Disease Among Chinese Adults: A China Multi-ethnic Cohort (CMEC) Study. 中国成年人铜锌比值与心血管疾病之间的关系:中国多民族队列(CMEC)研究》。
IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 Epub Date: 2024-08-12 DOI: 10.1007/s12012-024-09904-y
Yili Shen, Yuxin Hu, Leilei Liu, Jianqin Zhong, Yuxin Zhang, Shenyan Wu, Cheng Chen, Feng Hong

The impact of metal exposure on cardiovascular diseases has become an increasingly concerning topic. To date, few studies have investigated the relationship between the copper-to-zinc ratio and CVD (Cardiovascular disease). This China multi-ethnic cohort study explored the association between the copper-to-zinc ratio and CVD in Chinese adults. The study included a sample size of 9878 people. Logistic regression analysis was used to examine the correlation between urinary copper, urinary zinc, and the copper-to-zinc ratio and CVD prevalence. Restricted cubic spline (RCS) analysis was used to investigate the potential dose-response relationships among copper-to-zinc ratio, urinary copper, urinary zinc, and CVD prevalence. In addition, the least absolute shrinkage and selection operator (LASSO) regression method was used to identify significant risk factors associated with CVD, leading to the development of a nomogram. The predictive performance of the nomogram model for CVD was assessed using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Compared with the copper-to-zinc ratio in Q1, the copper-to-zinc ratio in Q4 was associated with CVD after adjusting for all potential confounders (Model 3) (Q4, odds ratio [OR] 0.608, 95% confidence interval [CI] 0.416-0.889, P = 0.010). After adjusting for all potential confounders (Model 3), urinary copper levels in Q4 were associated with CVD (Q4, odds ratio [OR] 0.627, 95% confidence interval [CI] 0.436-0.902, P = 0.012). No significant difference was found between urinary zinc levels and CVD. The RCS showed a linear dose-response relationship between the copper-to-zinc ratio and CVD (P for overall = 0.01). The nomogram based on the influencing factors examined with LASSO showed good predictive power, and the AUC was 76.3% (95% CI 73.7-78.9%). Our results suggest that there is a significant linear negative correlation between the copper-to-zinc ratio and CVD in Chinese adults and that it has good predictive value for CVD.

金属暴露对心血管疾病的影响已成为一个越来越受关注的话题。迄今为止,很少有研究调查铜锌比值与心血管疾病(CVD)之间的关系。这项中国多民族队列研究探讨了铜锌比值与中国成年人心血管疾病之间的关系。该研究的样本量为 9878 人。研究采用逻辑回归分析法来检验尿铜、尿锌、铜锌比值与心血管疾病患病率之间的相关性。限制立方样条(RCS)分析用于研究铜锌比值、尿铜、尿锌和心血管疾病患病率之间的潜在剂量反应关系。此外,还采用了最小绝对收缩和选择算子(LASSO)回归法来确定与心血管疾病相关的重要风险因素,从而建立了一个提名图。利用接收者操作特征曲线(ROC)和曲线下面积(AUC)评估了提名图模型对心血管疾病的预测性能。与第一季度的铜锌比值相比,第四季度的铜锌比值在调整所有潜在混杂因素(模型 3)后与心血管疾病相关(第四季度,几率比 [OR] 0.608,95% 置信区间 [CI] 0.416-0.889,P = 0.010)。调整所有潜在混杂因素(模型 3)后,第四季度的尿铜水平与心血管疾病相关(第四季度,几率比 [OR] 0.627,95% 置信区间 [CI] 0.436-0.902,P = 0.012)。尿锌水平与心血管疾病之间无明显差异。RCS显示铜锌比值与心血管疾病之间存在线性剂量反应关系(总体P = 0.01)。基于 LASSO 检测的影响因素的提名图显示出良好的预测能力,AUC 为 76.3% (95% CI 73.7-78.9%)。我们的研究结果表明,铜锌比值与中国成年人心血管疾病之间存在显著的线性负相关,对心血管疾病具有良好的预测价值。
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引用次数: 0
Potential Role of Dipeptidyl Peptidase-4 in Regulating Mitochondria and Oxidative Stress in Cardiomyocytes. 二肽基肽酶-4 在调节线粒体和心肌细胞氧化应激中的潜在作用
IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 Epub Date: 2024-07-02 DOI: 10.1007/s12012-024-09884-z
Shih-Yi Lee, Shao-Tung Wu, Chen-Xuan Du, Hui-Chun Ku

Oxidative stress causes mitochondrial damage and bioenergetic dysfunction and inhibits adenosine triphosphate production, contributing to the pathogenesis of cardiac diseases. Dipeptidyl peptidase 4 (DPP4) is primarily a membrane-bound extracellular peptidase that cleaves Xaa-Pro or Xaa-Ala dipeptides from the N terminus of polypeptides. DPP4 inhibitors have been used in patients with diabetes and heart failure; however, they have led to inconsistent results. Although the enzymatic properties of DPP4 have been well studied, the substrate-independent functions of DPP4 have not. In the present study, we knocked down DPP4 in cultured cardiomyocytes to exclude the effects of differential alteration in the substrates and metabolites of DPP4 then compared the response between the knocked-down and wild-type cardiomyocytes during exposure to oxidative stress. H2O2 exposure induced DPP4 expression in both types of cardiomyocytes. However, knocking down DPP4 substantially reduced the loss of cell viability by preserving mitochondrial bioenergy, reducing intracellular reactive oxygen species production, and reducing apoptosis-associated protein expression. These findings demonstrate that inhibiting DPP4 improves the body's defense against oxidative stress by enhancing Nrf2 and PGC-1α signaling and increasing superoxide dismutase and catalase activity. Our results indicate that DPP4 mediates the body's response to oxidative stress in individuals with heart disease.

氧化应激会造成线粒体损伤和生物能功能障碍,并抑制三磷酸腺苷的产生,从而导致心脏疾病的发病机理。二肽基肽酶 4(DPP4)主要是一种膜结合细胞外肽酶,可从多肽的 N 端裂解 Xaa-Pro 或 Xaa-Ala 二肽。DPP4 抑制剂已用于糖尿病和心力衰竭患者,但效果并不一致。尽管对 DPP4 的酶学特性进行了深入研究,但对 DPP4 与底物无关的功能却没有深入研究。在本研究中,我们敲除了培养的心肌细胞中的 DPP4,以排除 DPP4 底物和代谢产物的不同改变的影响,然后比较了被敲除的心肌细胞和野生型心肌细胞在暴露于氧化应激时的反应。H2O2暴露诱导了两种类型心肌细胞中DPP4的表达。然而,通过保护线粒体生物能、减少细胞内活性氧的产生和降低细胞凋亡相关蛋白的表达,敲除 DPP4 大大降低了细胞活力的丧失。这些研究结果表明,抑制 DPP4 可增强 Nrf2 和 PGC-1α 信号转导,提高超氧化物歧化酶和过氧化氢酶的活性,从而改善机体对氧化应激的防御能力。我们的研究结果表明,DPP4 在心脏病患者体内介导机体对氧化应激的反应。
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引用次数: 0
Association Between CYP2D7 and TCF20 Polymorphisms and Coronary Heart Disease. CYP2D7 和 TCF20 多态性与冠心病的关系
IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 Epub Date: 2024-07-26 DOI: 10.1007/s12012-024-09907-9
Wenjie Zhang, Panpan Wan, Man Zhang, Yanting Chang, Shuli Du, Tianbo Jin, Yuan Wang

One of the causes of coronary heart disease (CHD) is genetic factors. In this study, we explored the relationship between CYP2D7 and TCF20 gene polymorphisms and the risk of CHD in the Han Chinese population. Three single nucleotide polymorphisms (CYP2D7 rs1800754, CYP2D7 rs2743461, and TCF20 rs760648) were selected and genotyped from 490 cases and 480 controls. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between CYP2D7 and TCF20 polymorphisms and the risk of CHD. The association between clinical indicators and polymorphisms was analyzed using one-way ANOVA and Tukey's HSD. The SNP-SNP interactions were obtained by performing multifactor dimensionality reduction (MDR). CYP2D7 rs1800754 and rs2743461 were closely associated with increased risk of CHD (alleles: p = 0.014, p = 0.031). Stratified analysis showed that CYP2D7 rs1800754 and rs2743461 were associated with an increased risk of CHD in men, age > 60 years, BMI ≥ 24, and smoking. Rs1800754 is also associated with an increased risk of CHD associated with alcohol consumption. In addition, TCF20 rs760648 was associated with a reduced risk of CHD in patients aged ≤ 60 years and with CALs. A significant association was found between CYP2D7 rs1800754 and rs2743461 genotypes and levels of UREA, Cr, and LDL-C; TCF20 rs760648 genotypes and levels of RBC. The MDR analysis showed that the three-locus interaction model was the best in the multi-locus model. In conclusion, CYP2D7 rs1800754 and rs2743461 polymorphisms were associated with CHD risk.

冠心病(CHD)的病因之一是遗传因素。本研究探讨了中国汉族人群中 CYP2D7 和 TCF20 基因多态性与冠心病风险之间的关系。研究选取了 490 例病例和 480 例对照中的三个单核苷酸多态性(CYP2D7 rs1800754、CYP2D7 rs2743461 和 TCF20 rs760648)进行基因分型。采用几率比(ORs)和 95% 置信区间(CIs)来评估 CYP2D7 和 TCF20 多态性与冠心病风险之间的关系。临床指标与多态性之间的关联采用单因素方差分析和Tukey's HSD进行分析。通过多因素降维(MDR)获得了SNP-SNP相互作用。CYP2D7 rs1800754 和 rs2743461 与冠心病风险增加密切相关(等位基因:p = 0.014,p = 0.031)。分层分析表明,CYP2D7 rs1800754 和 rs2743461 与男性、年龄大于 60 岁、体重指数≥ 24 和吸烟者的冠心病风险增加有关。Rs1800754 还与饮酒导致的冠心病风险增加有关。此外,TCF20 rs760648 与年龄≤60 岁和有 CALs 的患者的冠心病风险降低有关。研究发现,CYP2D7 rs1800754和rs2743461基因型与UREA、Cr和LDL-C水平;TCF20 rs760648基因型与RBC水平之间存在明显关联。MDR 分析表明,三病灶交互作用模型在多病灶模型中是最好的。总之,CYP2D7 rs1800754和rs2743461多态性与冠心病风险相关。
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引用次数: 0
Association Between Nickel Exposure and Metabolic Syndrome: Data from NHANES 2017-2018. 镍暴露与代谢综合征之间的关系:来自 2017-2018 年 NHANES 的数据。
IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 Epub Date: 2024-08-13 DOI: 10.1007/s12012-024-09912-y
Xiao-Min Luo, Min Tang, Xiao-Hui Wei, Xiaofang Tang, Yong-De Peng

Previous studies have found a possible association between nickel and metabolic syndrome (MetS), but with conflicting results. No studies have determined whether nickel exposure increases the prevalence of MetS in the general U.S. population. Therefore, we used data from the National Health and Nutrition Examination Survey (NHANES) to assess the association between urinary nickel and MetS. Since urinary nickel levels were presented as a skewed distribution, they were normalized using a logarithmic transformation. Weighted multivariate logistic models, restricted cubic spline, threshold effect analysis, and subgroup analyses were used to examine the association between urinary nickel concentration and the risk of MetS and its components. Based on data from 1577 participants, individuals in the second, third, and fourth quartiles of urinary nickel had an adjusted OR for MetS of 1.42 (95% CI: 0.88, 2.28), 2.00 (95% CI: 1.22, 3.28), and 1.68 (95% CI: 1.05, 2.70), respectively, representing an inverted "L"-shaped nonlinear dose-response relationship with an inflection point at 0.2141 ng/L. Patients over the age of 40, males, less educated, and smokers are more susceptible to nickel exposure. In addition, there were significant associations between nickel and most components of the MetS, with the strongest to weakest correlations being high fasting glucose, reduced high-density lipoprotein, abdominal obesity, and elevated blood pressure; however, there was no significant correlation between nickel and hyperlipidemia. In conclusion, environmental nickel exposure increases the prevalence of MetS in U.S. adults, particularly in males over 40 years of age, those with less education, and smokers.

以往的研究发现,镍与代谢综合征(MetS)之间可能存在关联,但研究结果相互矛盾。目前还没有研究确定镍暴露是否会增加美国普通人群中 MetS 的患病率。因此,我们利用美国国家健康与营养调查(NHANES)的数据来评估尿镍与 MetS 之间的关系。由于尿镍水平呈偏态分布,因此采用对数变换对其进行归一化处理。采用加权多变量逻辑模型、限制性三次样条曲线、阈值效应分析和亚组分析来研究尿镍浓度与 MetS 风险及其组成部分之间的关系。根据 1577 名参与者的数据,尿镍浓度处于第二、第三和第四四分位数的人患 MetS 的调整后 OR 值分别为 1.42(95% CI:0.88,2.28)、2.00(95% CI:1.22,3.28)和 1.68(95% CI:1.05,2.70),呈现倒 "L "形的非线性剂量-反应关系,拐点为 0.2141 ng/L。年龄超过 40 岁、男性、教育程度较低和吸烟的患者更容易受到镍暴露的影响。此外,镍与 MetS 的大多数成分之间存在明显的相关性,从强到弱的相关性依次为空腹血糖高、高密度脂蛋白降低、腹部肥胖和血压升高;但是,镍与高脂血症之间没有明显的相关性。总之,环境中的镍暴露会增加美国成年人的 MetS 患病率,尤其是 40 岁以上的男性、教育程度较低的人群和吸烟者。
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引用次数: 0
Prevalence, Outcomes, and Predictors of Prolonged Corrected QT Interval in Hydroxychloroquine-Naïve Hospitalized COVID-19 Patients. 不使用羟氯喹的 COVID-19 住院患者校正 QT 间期延长的发生率、结果和预测因素。
IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 Epub Date: 2024-07-02 DOI: 10.1007/s12012-024-09886-x
Praveen Gupta, Anunay Gupta, Kapil Gupta, Sandeep Bansal, Monica Sharma, Ira Balakrishnan

The studies regarding prevalence, outcomes, and predictors of prolonged corrected QT (QTc) among COVID-19 patients not on QTc-prolonging medication are not available in the literature. In this retrospective cohort study, the QTc of 295 hospital-admitted COVID-19 patients was analyzed and its association with in-hospital mortality was determined. The QTc was prolonged in 14.6% (43/295) of the study population. Prolonged QTc was seen in patients with older age (P = 0.018), coronary artery disease (P = 0.001), congestive heart failure (P = 0.042), elevated N-terminal-pro-B-type natriuretic peptide (NT-ProBNP) (P < 0.0001), and on remdesivir (P = 0.046). No episode of torsades de pointes arrhythmia or any arrhythmic death was observed among patients with prolonged QTc. The mortality was significantly high in patients with prolonged QTc (P = 0.003). The multivariate logistic regression analysis showed coronary artery disease (odds ratio (OR): 4.153, 95% CI 1.37-14.86; P = 0.013), and NT-ProBNP (ng/L) (OR: 1.000, 95% CI 1.000-1.000; P = 0.007) as predictors of prolonged QTc. The prolonged QTc was associated with the worst in-hospital survival (p by log-rank 0.001). A significant independent association was observed between prolonged QTc and in-hospital mortality in multivariate cox-regression analysis (adjusted hazard ratio: 3.861; (95% CI 1.719-6.523), P < 0.0001). QTc was found to be a marker of underlying comorbidities among COVID-19 patients. Prolonged QTc in hospitalized COVID-19 patients was independently associated with in-hospital mortality.

有关未服用QTc延长药物的COVID-19患者中校正QT(QTc)延长的发生率、结果和预测因素的研究在文献中并不多见。在这项回顾性队列研究中,对 295 名入院的 COVID-19 患者的 QTc 进行了分析,并确定了其与院内死亡率的关系。研究人群中有 14.6%(43/295)的患者 QTc 延长。QTc延长见于年龄较大(P = 0.018)、患有冠状动脉疾病(P = 0.001)、充血性心力衰竭(P = 0.042)、N-末端前 B 型钠尿肽(NT-ProBNP)升高(P = 0.001)、N-末端前 B 型钠尿肽(NT-ProBNP)升高(P = 0.042)和N-末端前 B 型钠尿肽(NT-ProBNP)升高(P = 0.018)的患者。
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引用次数: 0
Circ_0005699 Expedites ox-LDL-Triggered Endothelial Cell Injury via Targeting miR-384/ASPH Axis. Circ_0005699 通过靶向 miR-384/ASPH 轴加速 ox-LDL 触发的内皮细胞损伤
IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 Epub Date: 2024-07-08 DOI: 10.1007/s12012-024-09889-8
Xiaobiao Cao, Jun Yang, Lujun He, Cangcang Liu

Atherosclerosis (AS) is an inflammatory disease with multiple causes. Multiple circular RNAs (circRNAs) are known to be involved in the pathogenesis of AS. To explore the function and mechanism of circ_0005699 in oxidative low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) injury. Ox-LDL treatment restrained HUVECs viability, cell proliferation, and angiogenesis ability, and accelerated HUVECs apoptosis, inflammatory response, and oxidative stress. Circ_0005699 was up-regulated in the serum samples of AS patients and ox-LDL-induced HUVECs. Interference of circ_0005699 effectively rescued ox-LDL-induced injury in HUVECs. Additionally, miR-384 could bind to circ_0005699, and miR-384 depletion inverted the effects of circ_0005699 deficiency on ox-LDL-mediated HUVEC injury. Moreover, ASPH was a direct target of miR-384, and the enforced expression of ASPH overturned miR-384-induced effects on ox-LDL-induced HUVECs. Importantly, circ_0005699 regulated ASPH expression via sponging miR-384. Interference of circ_0005699 protected against ox-LDL-induced injury in HUVECs at least partly by regulating ASPH expression via acting as a miR-384 sponge.

动脉粥样硬化(AS)是一种有多种病因的炎症性疾病。已知多种环状 RNA(circRNA)参与了动脉粥样硬化的发病机制。目的:探讨 circ_0005699 在氧化性低密度脂蛋白(ox-LDL)诱导的人脐静脉内皮细胞(HUVECs)损伤中的功能和机制。Ox-LDL 处理抑制了 HUVECs 的活力、细胞增殖和血管生成能力,并加速了 HUVECs 的细胞凋亡、炎症反应和氧化应激。Circ_0005699在强直性脊柱炎患者和氧化-LDL诱导的HUVECs血清样本中上调。干扰circ_0005699可有效缓解氧化-LDL诱导的HUVEC损伤。此外,miR-384能与circ_0005699结合,miR-384的缺失能逆转circ_0005699缺乏对ox-LDL介导的HUVEC损伤的影响。此外,ASPH 是 miR-384 的直接靶标,ASPH 的强制表达推翻了 miR-384 诱导的对 ox-LDL 诱导的 HUVEC 的影响。重要的是,circ_0005699 通过疏导 miR-384 来调控 ASPH 的表达。对circ_0005699的干扰至少部分是通过充当miR-384的海绵来调节ASPH的表达,从而保护HUVEC免受ox-LDL诱导的损伤。
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引用次数: 0
Disruption of BACH1 Protects AC16 Cardiomyocytes Against Hypoxia/Reoxygenation-Evoked Injury by Diminishing CDKN3 Transcription. 通过减少 CDKN3 的转录,中断 BACH1 可保护 AC16 心肌细胞免受缺氧/再氧诱发的损伤。
IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 Epub Date: 2024-07-26 DOI: 10.1007/s12012-024-09900-2
Yanping Li, Yi Zhou, Haifeng Pei, De Li

Reperfusion after myocardial infarction (MI) can lead to myocardial ischemia/reperfusion (I/R) damage. The transcription factor (TF) broad-complex, tramtrack, and bric-a-brac (BTB) and cap'n'collar (CNC) homology 1 (BACH1) is implicated in the injury. However, the downstream mechanisms of BACH1 in affecting myocardial hypoxia/reoxygenation (H/R) damage are still fully understood. AC16 cells were stimulated with H/R conditions to model cardiomyocytes under H/R. mRNA analysis was performed by quantitative real-time PCR. Protein levels were gauged by immunoblot analysis. The effect of BACH1/cyclin-dependent kinase inhibitor 3 (CDKN3) on H/R-evoked injury was assessed by measuring cell viability via Cell Counting Kit-8 (CCK-8), apoptosis (flow cytometry and caspase 3 activity), ferroptosis via Fe2+, glutathione (GSH), reactive oxygen species (ROS) and malondialdehyde (MDA) markers and inflammation cytokines interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNF-α). The BACH1/CDKN3 relationship was examined by chromatin immunoprecipitation (ChIP) experiment and luciferase assay. BACH1 was increased in MI serum and H/R-stimulated AC16 cardiomyocytes. Functionally, disruption of BACH1 mitigated H/R-evoked in vitro apoptosis, ferroptosis and inflammation of AC16 cardiomyocytes. Mechanistically, BACH1 activated CDKN3 transcription and enhanced CDKN3 protein expression in AC16 cardiomyocytes. Our rescue experiments validated that BACH1 disruption attenuated H/R-evoked AC16 cardiomyocyte apoptosis, ferroptosis and inflammation by downregulating CDKN3. Additionally, BACH1 disruption could activate the adenosine monophosphate-activated protein kinase (AMPK) signaling by downregulating CDKN3 in H/R-stimulated AC16 cardiomyocytes. Our study demonstrates that BACH1 activates CDKN3 transcription to induce H/R-evoked damage of AC16 cardiomyocytes partially via AMPK signaling.

心肌梗塞(MI)后的再灌注可导致心肌缺血/再灌注(I/R)损伤。转录因子(TF)broad-complex、tramtrack、and bric-a-brac (BTB) and cap'n'collar (CNC) homology 1 (BACH1)与这种损伤有关。然而,BACH1影响心肌缺氧/再氧合(H/R)损伤的下游机制仍不完全清楚。用实时定量 PCR 分析 mRNA。蛋白质水平通过免疫印迹分析测定。通过细胞计数试剂盒-8(CCK-8)测量细胞活力、细胞凋亡(流式细胞术和 caspase 3 活性),评估 BACH1/细胞周期蛋白依赖性激酶抑制剂 3(CDKN3)对 H/R 诱发损伤的影响、通过Fe2+、谷胱甘肽(GSH)、活性氧(ROS)和丙二醛(MDA)标记物以及炎症细胞因子白细胞介素-1β(IL-1β)和肿瘤坏死因子α(TNF-α)来评估铁变态反应。通过染色质免疫沉淀(ChIP)实验和荧光素酶检测,研究了BACH1/CDKN3之间的关系。BACH1在MI血清和H/R刺激的AC16心肌细胞中增加。从功能上讲,破坏 BACH1 可减轻 H/R 引起的 AC16 心肌细胞体外凋亡、铁突变和炎症。从机制上讲,BACH1激活了AC16心肌细胞中CDKN3的转录并增强了CDKN3蛋白的表达。我们的抢救实验证实,BACH1中断可通过下调CDKN3减轻H/R诱发的AC16心肌细胞凋亡、铁突变和炎症。此外,在H/R刺激的AC16心肌细胞中,BACH1中断可通过下调CDKN3激活单磷酸腺苷激活蛋白激酶(AMPK)信号。我们的研究表明,BACH1可激活CDKN3转录,部分通过AMPK信号诱导AC16心肌细胞的H/R诱发损伤。
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引用次数: 0
Diagnostic and Predictive Value of LncRNA MCM3AP-AS1 in Sepsis and Its Regulatory Role in Sepsis-Induced Myocardial Dysfunction. 脓毒症中 LncRNA MCM3AP-AS1 的诊断和预测价值及其在脓毒症诱发的心肌功能障碍中的调控作用
IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI: 10.1007/s12012-024-09903-z
Yunwei Wei, Cui Bai, Shuying Xu, Mingli Cui, Ruixia Wang, Meizhen Wu

The present study focused on exploring the clinical value and molecular mechanism of LncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) in sepsis and sepsis-induced myocardial dysfunction (SIMD). 122 sepsis patients and 90 healthy were included. Sepsis patients were categorized into SIMD and non-MD. The expression levels of MCM3AP-AS1 and miRNA were examined using RT-qPCR. Diagnostic value of MCM3AP-AS1 in sepsis assessed by ROC curves. Logistic regression to explore risk factors influencing the occurrence of SIMD. Cardiomyocytes were induced by LPS to construct cell models in vitro. CCK-8, flow cytometry, and ELISA to analyze cell viability, apoptosis, and inflammation levels. Serum MCM3AP-AS1 was upregulated in patients with sepsis. The sensitivity and specificity of MCM3AP-AS1 were 75.41% and 93.33%, for recognizing sepsis from healthy controls. Additionally, elevated MCM3AP-AS1 is a risk factor for SIMD and can predict SIMD development. Compared with the LPS-induced cardiomyocytes, inhibition of MCM3AP-AS1 significantly attenuated LPS-induced apoptosis and inflammation; however, this attenuation was partially reversed by lowered miR-28-5p, but this reversal was partially eliminated by CASP2. MCM3AP-AS1 may be a novel diagnostic biomarker for sepsis and can predict the development of SIMD. MCM3AP-AS1 probably participated in SIMD progression by regulating cardiomyocyte inflammation and apoptosis through the target miR-28-5p/CASP2 axis.

本研究主要探讨LncRNA MCM3AP反义RNA 1(MCM3AP-AS1)在脓毒症和脓毒症诱发心肌功能障碍(SIMD)中的临床价值和分子机制。研究纳入了 122 名败血症患者和 90 名健康人。脓毒症患者分为 SIMD 和非 SIMD 两类。采用 RT-qPCR 方法检测了 MCM3AP-AS1 和 miRNA 的表达水平。通过 ROC 曲线评估 MCM3AP-AS1 在败血症中的诊断价值。通过逻辑回归探讨影响 SIMD 发生的风险因素。用 LPS 诱导心肌细胞在体外构建细胞模型。用 CCK-8、流式细胞术和 ELISA 分析细胞活力、凋亡和炎症水平。脓毒症患者血清中的 MCM3AP-AS1 上调。MCM3AP-AS1从健康对照组中识别败血症的敏感性和特异性分别为75.41%和93.33%。此外,MCM3AP-AS1 的升高是 SIMD 的一个危险因素,可以预测 SIMD 的发展。与LPS诱导的心肌细胞相比,抑制MCM3AP-AS1可显著减轻LPS诱导的细胞凋亡和炎症反应;然而,降低miR-28-5p可部分逆转这种减轻作用,但CASP2可部分消除这种逆转作用。MCM3AP-AS1可能是败血症的一种新型诊断生物标志物,并能预测SIMD的发展。MCM3AP-AS1可能通过靶标miR-28-5p/CASP2轴调节心肌细胞炎症和凋亡,从而参与SIMD的进展。
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引用次数: 0
Protective Effect of Berberine Nanoparticles Against Cardiotoxic Effects of Arsenic Trioxide. 小檗碱纳米颗粒对三氧化二砷心脏毒性效应的保护作用
IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-30 DOI: 10.1007/s12012-024-09927-5
Seyed Hadi Hosseini, Maryam Nazarian, Shahnaz Rajabi, Amir Masoud Jafari-Nozad, Behzad Mesbahzadeh, Saeed Samargahndian, Tahereh Farkhondeh

Arsenic trioxide (ATO) is a potent and highly effective chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, the clinical use of ATO is hampered by different cardiopathologic outcomes, such as arrhythmia and heart failure. Berberine has several beneficial effects because of its antioxidant activity; however, the potential cardioprotective function of this alkaloid against arsenic-induced cardiac toxicity has not been fully investigated. In this study, we evaluated the effect of ATO in rat heart tissue and the effect of berberine nanoparticles (NB) on cardiac enzyme levels, oxidative stress (OS) indices, and histopathological changes in heart tissue. Thirty Wistar rats were randomly allocated into five groups (n = 6): (1) Control animals that received 0.5 cc saline via gavage, (2) ATO group (4 mg/kg), (3) ATO + NB (2.5 mg/kg), (4) ATO + NB (5 mg/kg), and (5) ATO + NB (10 mg/kg) groups. Treatments were administered intraperitoneally for 45 days. Cardiac enzymes and OS biomarkers in heart tissue were measured. Histopathological examination of the heart tissue was also conducted at the end of the study. ATO injection significantly increased cardiac enzyme levels and OS biomarkers in rat's heart tissue. It also changed the histological features of the heart. NB administration significantly decreased the serum and tissue levels of cardiac enzyme and OS biomarkers in ATO-exposed animals (p < 0.05) and improved myocardial structural damage. NB, potent antioxidant, can reduce the unfavorable effects of ATO in rat heart tissue by balancing OS markers.

三氧化二砷(ATO)是治疗急性早幼粒细胞白血病的强效化疗药物。然而,三氧化二砷在临床上的应用却受到心律失常和心力衰竭等不同心脏病理结果的阻碍。小檗碱具有抗氧化活性,因此有多种有益的作用;然而,这种生物碱对砷引起的心脏毒性的潜在心脏保护功能尚未得到充分研究。在这项研究中,我们评估了砷化钾对大鼠心脏组织的影响,以及小檗碱纳米颗粒(NB)对心脏酶水平、氧化应激(OS)指数和心脏组织病理变化的影响。将 30 只 Wistar 大鼠随机分为 5 组(n = 6):(1) 对照组,灌胃 0.5 cc 生理盐水;(2) ATO 组(4 mg/kg);(3) ATO + NB 组(2.5 mg/kg);(4) ATO + NB 组(5 mg/kg);(5) ATO + NB 组(10 mg/kg)。腹腔注射治疗 45 天。测量心脏组织中的心肌酶和操作系统生物标志物。研究结束时还对心脏组织进行了组织病理学检查。注射 ATO 后,大鼠心脏组织中的心肌酶水平和 OS 生物标志物明显增加。它还改变了心脏的组织学特征。注射 NB 能明显降低 ATO 暴露动物血清和组织中的心肌酶和操作系统生物标志物水平(p < 0.05),并改善心肌结构损伤。NB是一种强效抗氧化剂,可通过平衡OS标志物减轻ATO对大鼠心脏组织的不利影响。
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引用次数: 0
Unveiling the Mechanism of Protective Effects of Tanshinone as a New Fighter Against Cardiovascular Diseases: A Systematic Review. 揭示丹参酮作为心血管疾病新斗士的保护作用机制:系统综述。
IF 3.4 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-09-22 DOI: 10.1007/s12012-024-09921-x
Mohammad Mahdi Dabbaghi, Hesan Soleimani Roudi, Rozhan Safaei, Vafa Baradaran Rahimi, Mohammad Reza Fadaei, Vahid Reza Askari

Tanshinone, a natural compound found in the roots of Salvia miltiorrhiza, has been shown to possess various pharmacological properties, including anti-inflammatory, antioxidant, and cardiovascular protective effects. This article aims to review the literature on the cardiovascular protective effects of tanshinone and its underlying mechanisms. Tanshinone has been demonstrated to improve cardiac function, reduce oxidative stress, and inhibit inflammation in various animal models of cardiovascular diseases. Additionally, it has been shown to regulate multiple signaling pathways involved in the pathogenesis of cardiovascular diseases, such as the PI3K/AKT, MAPK, and NF-κB pathways. Clinical studies have also suggested that tanshinone may have therapeutic potential for treating cardiovascular diseases. In conclusion, tanshinone has emerged as a promising natural compound with significant cardiovascular protective effects, and further research is warranted to explore its potential clinical applications.

丹参酮是一种存在于丹参根部的天然化合物,已被证明具有多种药理特性,包括抗炎、抗氧化和心血管保护作用。本文旨在对丹参酮的心血管保护作用及其内在机制的文献进行综述。在各种心血管疾病动物模型中,丹参酮已被证实具有改善心脏功能、减少氧化应激和抑制炎症的作用。此外,丹参酮还能调节心血管疾病发病机制中的多种信号通路,如 PI3K/AKT、MAPK 和 NF-κB 通路。临床研究也表明丹参酮具有治疗心血管疾病的潜力。总之,丹参酮是一种很有前景的天然化合物,具有显著的心血管保护作用,我们需要进一步研究探索其潜在的临床应用。
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引用次数: 0
期刊
Cardiovascular Toxicology
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