Roles of catalase and cytochrome C in hydroperoxide-dependent lipid peroxidation and chemiluminescence in rat heart and kidney mitochondria

A recent report (Radi et al., J. Biol. Chem. 266:22028–22034, 1991) showed that rat heart mitochondria contain catalase. The protective role of mitochondrial catalase was tested by exposing heart or kidney mitochondria and mitoplasts to two oxidants (H₂O₂) or tert-butyl hydroperoxide, t-BOOH), estimating lipid peroxidation (as thiobarbituric acid-reactive substances, TBARS) and overall oxidative stress (as chemiluminescence). Additional controls included heart and kidney preparations from aminotriazole-treated (catalase-depleted) rats. Both oxidants increased TBARS in catalase-free preparations to similar extents over their respective controls (between 200 to 350%). In catalase-containing preparations, H₂O₂ lipid peroxidation increased by only 40 to 96% over controls. Similar qualitative results were obtained when measuring chemiluminescence. The catalytic role of cytochrome c in mitochondrial lipid peroxidation was investigated by exposing either control or cytochrome-c-depleted kidney mitoplasts (catalase free) to either H₂O₂ or t-BOOH. Hydrogen-peroxide-dependent mitochondrial lipid peroxidation varied with cytochrome c concentrations, remaining close to controls when cytochrome c concentration decreased by 66%, even though there was no catalase present. Tert-butyl hydroperoxide-dependent lipid peroxidation was less affected by cytochrome c remaining 2.3-fold above controls under the same conditions, suggesting that organic peroxides are more likely to remain in the less polar membrane environment being decomposed by heme or nonheme iron imbedded in the inner mitochondrial membrane. Chemiluminescence was less affected by cytochrome c depletion. Comparing control and cytochrome-c-deficient mitochondria, chemiluminescence was 1.7-fold and 2.8-fold higher when control preparations were challenged with t-BOOH or H₂O₂, respectively.     

Prevalence of transthyretin cardiac amyloidosis in elderly patients diagnosed with heart failure

ObjectiveThere is increased interest in studying ATTR-CA, a pathology that primarily affects patients of geriatric age and is frequently underdiagnosed. We aim to establish the prevalence of ATTR-CA in a cohort of patients with a history of HFpEF and to describe its characteristics.MethodsWe conducted a prospective observational study. Patients ≥75 years, clinical history of HFpEF, atrial dilation ≥34 ml/m² and left ventricular wall thickening >13 mm, were included. Demographic and analytical parameters were collected, and a comprehensive geriatric assessment was performed, along with a transthoracic echocardiogram and cardiac scintigraphy. Finally, telephone follow-up was carried out at 6 and 12 months.Results50 patients were recruited, mean age 86 ± 6 years, 54% women. Age and functional class (I–II vs. III–IV) were factors associated with presenting with ATTR-CA. Patients with positive scintigraphy had a median time to admission of 5.2 months (confidence interval [CI] 95% 0–10.9), while in those with negative scintigraphy, it was 12.2 months (95% CI 11.7–12.8); log-rank: p = 0.064. Patients with positive scintigraphy had a median time to the combined endpoint (death and readmission) of 1.9 months (95% CI 0–6.1), and patients with negative scintigraphy of 11.9 months (95% CI 11.7–12); log-rank: p = 0.027.ConclusionsATTR-CA appears to be a prevalent etiology in elderly patients within the spectrum of HFpEF. Patients with a diagnosis of ATTR-CA had a shorter time to admission for HF and the combined event of death and admission than patients with a negative result on scintigraphy.     

血清NEP、PTX3及H-FABP在慢性心力衰竭的表达水平及与疾病的相关性分析

摘要 目的：探讨血清脑啡肽酶（NEP）、正五聚蛋白3（PTX3）及心型脂肪酸结合蛋白（H-FABP）在慢性心力衰竭（CHF）的表达水平及其与疾病严重程度的相关性。方法：选入我院2019年10月~2021年10月收治的110例CHF患者作为观察组,并根据美国纽约心脏病学会（NYHA）标准进行心功能分级,另取同期健康志愿者50例作为对照组。比较两组之间、观察组不同心功能分级之间的血清NEP、PTX3及H-FABP的表达水平,并分析三者与CHF严重程度的相关性。出院后随访90 d,记录主要心脏不良事件（MACE）情况。结果：观察组血清NEP和LVEF水平明显低于对照组（P＜0.05）,而PTX3、H-FABP及LVEDD显著高于对照组（P＜0.05）;且随着NYHA分级升高,NEP和LVEF逐渐降低（P＜0.05）,PTX3、H-FABP及LVEDD逐渐提高（P＜0.05）,各组间差异显著（P＜0.05）;相关性分析结果显示：PTX3、H-FABP与NYHA分级和LVEDD存在明显正相关（P<0.05）,与LVEF呈明显负相关（P<0.05）,NEP与NYHA分级、LVEF和LVEDD均无明显相关性（P＞0.05）。MACE患者血清NEP水平显著低于非MACE患者,血清PTX3和H-FABP水平显著高于非MACE患者,差异有显著意义（P＜0.05）。结论：血清NEP、PTX3和H-FABP均是CHF诊断的重要生物学标志物,尤其是PTX3和H-FABP与病情严重程度和预后存在密切关系,联合检测对CHF早期诊断、病情和预后评估具有重要意义。     

血清SIRT1水平与射血分数保留的心力衰竭患者炎性因子、氧化应激的相关性分析及对预后的影响研究

摘要 目的：探讨血清去乙酰化酶1（SIRT1） 水平与射血分数保留的心力衰竭（HFpEF）患者炎性因子、氧化应激的相关性,分析SIRT1预测HFpEF患者预后的价值。方法：选择2019年10月至2021年6月青岛阜外心血管病医院收治的190例HFpEF患者为HFpEF组,92例心功能正常的健康体检志愿者为对照组。HFpEF患者出院后随访12个月,统计随访期间不良心血管事件发生情况,多因素Logistic回归分析HFpEF患者预后不良的影响因素。结果：HFpEF组血清SIRT1水平低于对照组（P＜0.05）,白细胞介素（IL）-6、肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）、丙二醛（MDA）、晚期氧化蛋白产物（AOPP）水平高于对照组（P＜0.05）。HFpEF患者血清SIRT1水平与IL-6、TNF-α、CRP、MDA、AOPP呈负相关（r=-0.496、-0.502、-0.419、-0.533、-0.542,P＜0.05）。190例患者2例失访,余188例HFpEF患者中41例预后不良,147例预后良好。预后不良组美国纽约心脏病协会（NYHA）Ⅳ级比例、IL-6、TNF-α、CRP、MDA、AOPP、N末端B型利钠肽前体（NT-proBNP）水平、左室收缩末期内径（LVEDS）、左室舒张末期内径（LVEDD）、二尖瓣舒张早期血流峰值（E）与舒张晚期血流峰值（A）（E/A）高于预后良好组（P＜0.05）,血清SIRT1水平、左心室射血分数（LVEF）低于预后良好组（P＜0.05）。高IL-6、高MDA、高NT-proBNP是HFpEF患者预后不良的危险因素（P＜0.05）,SIRT1是HFpEF患者预后不良的保护因素（P＜0.05）。结论：HFpEF患者血清SIRT1水平降低,与HFpEF患者炎症反应、氧化应激以及预后不良的发生有关,可作为HFpEF患者预后评估的辅助指标。     

心元胶囊对慢性心力衰竭心血瘀阻证患者心脏超声参数、脂质代谢及血液流变学的影响

摘要 目的：探讨心元胶囊对慢性心力衰竭（CHF）心血瘀阻证患者心脏超声参数、脂质代谢及血液流变学的影响。方法：根据随机数字表法,将我院2020年3月~2022年3月期间收治的的CHF心血瘀阻证患者120例分为对照组（常规西药治疗,n=60）和观察组（心元胶囊联合常规西药治疗,n=60）。对比两组中医疗效、心功能指标、血脂指标、肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、N-末端脑钠肽前体（NT-proBNP）、血液流变学指标,并观察两组不良反应情况。结果：观察组的中医总有效率明显高于对照组（P<0.05）。两组治疗后左室射血分数升高,左室舒张末期容量、左室收缩末期容量缩小,且观察组的改善效果优于对照组（P<0.05）。两组治疗后三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）下降,高密度脂蛋白胆固醇（HDL-C）升高,且观察组的改善效果优于对照组（P<0.05）。两组治疗后CK、CK-MB、NT-proBNP下降,且观察组的改善效果优于对照组（P<0.05）。两组治疗后全血高切黏度、全血低切黏度、血浆黏度、纤维蛋白原下降,且观察组的改善效果优于对照组（P<0.05）。两组不良反应发生率对比,差异无统计学意义（P>0.05）。结论：心元胶囊治疗CHF心血瘀阻证可提高临床疗效,改善心功能,调节脂质代谢、血液流变学水平,安全有效。     

右美托咪定联合芬太尼对心脏瓣膜置换术患者细胞免疫功能的影响及心脑保护作用研究

摘要 目的：观察右美托咪定联合芬太尼对心脏瓣膜置换术患者细胞免疫功能的影响及在心脑保护中的作用。方法：纳入海南医学院第二附属医院2019年4月~2021年6月间接收的体外循环（CPB）下心脏瓣膜置换术患者97例,根据信封抽签法将患者分为对照组（芬太尼,48例）和观察组（右美托咪定联合芬太尼,49例）。对比两组血流动力学指标[平均动脉压（MAP）、心率（HR）]、心肌损伤指标[肌钙蛋白（cTnI）、肌酸激酶同工酶（CK-MB）、心型脂肪酸结合蛋白（HFABP）]、脑损伤指标[神经元特异性烯醇化酶（NSE）、S-100β]、细胞免疫功能、镇痛情况及不良反应发生率。结果：观察组CPB开始后10 min（T2）时间点HR、MAP低于对照组,CPB结束（T3）、术毕（T4）时间点HR、MAP高于对照组（P<0.05）。两组术前（T1）、术后24 h、术后48 h视觉模拟评分法（VAS）评分升高后降低（P<0.05）,观察组术后24 h、术后48 h VAS评分低于对照组（P<0.05）。观察组术后48 h CD4⁺、CD4⁺/CD8⁺高于对照组,CD8⁺低于对照组（P<0.05）。观察组术后48 h cTnI、CK-MB、HFABP低于对照组（P<0.05）。观察组术后48 h NSE、S100B低于对照组（P<0.05）。观察组的不良反应发生率低于对照组（P<0.05）。结论：心脏瓣膜置换术患者选用右美托咪定联合芬太尼麻醉方案,有助于减轻疼痛,稳定血流动力学,减轻免疫抑制,同时还可发挥心脑保护效果,降低不良反应发生率,是一种可靠的麻醉方案。     

铜蓝蛋白、鳞状细胞癌相关抗原与慢性肾功能衰竭的关系及对病情进展的预测价值研究

摘要 目的：分析铜蓝蛋白（CER）、鳞状细胞癌相关抗原（SCCA）与慢性肾功能衰竭的关系及对病情进展的预测价值。方法：选择我院自2019年4月至2021年4月接诊的169例慢性肾功能衰竭患者作为研究对象,根据24 h尿白蛋白定量分为微量白蛋白尿组（＜200 mg/24 h,102例）和大量白蛋白尿组（＞200 mg/24 h,67例）。比较两组各项实验室指标及血清CER、SCCA水平,分析CER、SCCA与慢性肾功能衰竭患者肾功能指标的关系。随访12个月,观察病情进展,使用受试者工作特征曲线（ROC）评价血清CER联合SCCA对病情进展的预测效能。结果：大量白蛋白尿组血清肌酐（Scr）、血尿素氮（BUN）水平均明显高于微量白蛋白尿组,肾小球滤过率（GFR）低于微量白蛋白尿组（P＜0.05）;大量白蛋白尿组血清CER、SCCA水平均高于微量白蛋白尿组（P＜0.05）;经Pearson相关性分析,慢性肾功能衰竭患者血清CER、SCCA水平均与Scr、BUN呈正相关,与GFR呈负相关（P＜0.05）;经多因素Logistic回归分析,GFR、CER、SCCA均是慢性肾功能衰竭患者病情进展的独立预测因素（P＜0.05）;经ROC曲线分析,血清CER联合SCCA预测慢性肾功能衰竭患者病情进展的AUC为0.925,明显大于GFR的0.620（P＜0.05）。结论：血清CER、SCCA水平与慢性肾功能衰竭患者肾功能呈负相关,联合预测病情进展效能较好,值得临床予以重视应用。     

经鼻加温加湿高流量吸氧对重症肺炎伴呼吸衰竭患儿血气指标、肺功能及细胞因子水平的影响

摘要 目的：观察经鼻加温加湿高流量吸氧（HFNC）对重症肺炎伴呼吸衰竭患儿血气指标、肺功能及细胞因子水平的影响。方法：选取南京医科大学附属儿童医院2020年3月~2022年3月期间收治的86例重症肺炎伴呼吸衰竭患儿,按照随机数字表法分为经鼻持续气道正压通气（nCPAP）组和HFNC组,各为43例。对比两组临床相关指标、血气指标、肺功能及细胞因子水平,同时观察两组镇静剂使用、预后及并发症发生情况。结果：HFNC组的机械通气时间、咳嗽缓解时间、肺部啰音消失时间、入住儿童重症监护室（PICU）时间均短于nCPAP组（P<0.05）。两组患儿治疗后心率（HR）升高,呼吸频率（RR）下降,且HFNC组的变化大于nCPAP组（P<0.05）。两组患儿治疗后pH值、血氧分压（PO₂）、血氧饱和度（SpO₂）、氧合指数（OI）均升高,且HFNC组高于nCPAP组（P<0.05）。两组患儿治疗后用力肺活量（FVC）、1s用力呼气容积（FEV1）、用力呼气时最高呼气流速（PEF）升高,且HFNC组高于nCPAP组（P<0.05）。两组患儿治疗后降钙素原（PCT）、白细胞介素（IL-6）和肿瘤坏死因子（TNF-α）下降,且HFNC组低于nCPAP组（P<0.05）。HFNC组镇静剂使用、再住院例数均少于nCPAP组（P<0.05）。两组死亡例数、并发症发生率组间对比未见统计学差异（P>0.05）。结论：HFNC可有效缓解重症肺炎伴呼吸衰竭患儿的临床症状,改善血气指标、肺功能及细胞因子水平。     

Planar cell polarity regulators in asymmetric organogenesis during development and disease

The phenomenon of planar cell polarity is critically required for a myriad of morphogenetic processes in metazoan and is accurately controlled by several conserved modules. Six “core” proteins, including Frizzled, Flamingo (Celsr), Van Gogh (Vangl), Dishevelled, Prickle, and Diego (Ankrd6), are major components of the Wnt/planar cell polarity pathway. The Fat/Dchs protocadherins and the Scrib polarity complex also function to instruct cellular polarization. In vertebrates, all these pathways are essential for tissue and organ morphogenesis, such as neural tube closure, left–right symmetry breaking, heart and gut morphogenesis, lung and kidney branching, stereociliary bundle orientation, and proximal–distal limb elongation. Mutations in planar polarity genes are closely linked to various congenital diseases. Striking advances have been made in deciphering their contribution to the establishment of spatially oriented pattern in developing organs and the maintenance of tissue homeostasis. The challenge remains to clarify the complex interplay of different polarity pathways in organogenesis and the link of cell polarity to cell fate specification. Interdisciplinary approaches are also important to understand the roles of mechanical forces in coupling cellular polarization and differentiation. This review outlines current advances on planar polarity regulators in asymmetric organ formation, with the aim to identify questions that deserve further investigation.     

Stress activated cytokines and the heart

The ability of myocardium to successfully compensate for, and adapt to, stress ultimately determines whether the heart will decompensate and fail, or whether it will instead maintain preserved function. Despite the importance of the myocardial response to environmental stress, very little is known with respect to the biochemical mechanisms that are responsible for mediating and integrating the stress response in the heart. In the present review we will summarize recent experimental material which suggests that cytokines that are expressed within the myocardium in response to a environment injury, namely tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6), may play an important role in initiating and integrating homeostatic responses within the heart. However, these ‘stress-activated’ cytokines all have the potential to produce cardiac decompensation when expressed at sufficiently high concentrations. Accordingly, the theme that will emerge from this discussion is that the short-term expression of stress-activated cytokines within the heart may provide the heart with an adaptive response to stress, whereas long-term expression of these molecules may be frankly maladaptive by producing cardiac decompensation.