Heart Protection

  • 文章类型: Journal Article
    热休克蛋白(HSPs),作为监护人,被激活以响应各种环境压力。除了它们在蛋白质生产的各个方面的作用,HSPs可防止有害的蛋白质相关应激源。木脂素表现出许多有益的性质。本研究旨在探讨毛囊素在热休克心脏中的保护作用,并确定其潜在机制。H9c2细胞,westernblot,TUNEL染色,流式细胞术,和免疫荧光染色。使用蛋白质印迹分析的热休克的时间依赖性效应显示HSP表达增加高达2[公式:见文本]h,随后在4[公式:见文本]h后进行蛋白质降解。因此,选择热冲击损伤持续时间为4[公式:参见文本]h用于后续研究。在热休克后施用的花叶素证明了细胞活力的剂量依赖性恢复。在热冲击条件下,calycosin通过上调HSPs阻止H9c2细胞凋亡,抑制p-JNK,增强Bcl-2激活,并抑制裂解的胱天蛋白酶3.毛黄蛋白酶还抑制Fas/FasL表达和激活的细胞存活标志物(p-PI3K,p-ERK,p-Akt),通过PI3K/Akt激活和JNK抑制表明它们的细胞保护特性。TUNEL染色和流式细胞术证实calycosin减少细胞凋亡。此外,环毛素逆转槲皮素对HSF1和Hsp70表达的抑制作用,说明其在热休克期间通过HSF1激活增强Hsp70表达中的作用。免疫荧光染色显示HSF1易位到细胞核后,强调其细胞保护作用。总之,calycosin通过调节HSP表达和调节关键信号通路以促进H9c2细胞的细胞存活,对热休克诱导的损伤具有明显的保护作用。
    Heat shock proteins (HSPs), which function as chaperones, are activated in response to various environmental stressors. In addition to their role in diverse aspects of protein production, HSPs protect against harmful protein-related stressors. Calycosin exhibits numerous beneficial properties. This study aims to explore the protective effects of calycosin in the heart under heat shock and determine its underlying mechanism. H9c2 cells, western blot, TUNEL staining, flow cytometry, and immunofluorescence staining were used. The time-dependent effects of heat shock analyzed using western blot revealed increased HSP expression for up to 2[Formula: see text]h, followed by protein degradation after 4[Formula: see text]h. Hence, a heat shock damage duration of 4[Formula: see text]h was chosen for subsequent investigations. Calycosin administered post-heat shock demonstrated dose-dependent recovery of cell viability. Under heat shock conditions, calycosin prevented the apoptosis of H9c2 cells by upregulating HSPs, suppressing p-JNK, enhancing Bcl-2 activation, and inhibiting cleaved caspase 3. Calycosin also inhibited Fas/FasL expression and activated cell survival markers (p-PI3K, p-ERK, p-Akt), indicating their cytoprotective properties through PI3K/Akt activation and JNK inhibition. TUNEL staining and flow cytometry confirmed that calycosin reduced apoptosis. Moreover, calycosin reversed the inhibitory effects of quercetin on HSF1 and Hsp70 expression, illustrating its role in enhancing Hsp70 expression through HSF1 activation during heat shock. Immunofluorescence staining demonstrated HSF1 translocation to the nucleus following calycosin treatment, emphasizing its cytoprotective effects. In conclusion, calycosin exhibits pronounced protective effects against heat shock-induced damages by modulating HSP expression and regulating key signaling pathways to promote cell survival in H9c2 cells.
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  • 文章类型: Journal Article
    放射性心脏病(RIHD)以严重的氧化应激和免疫失调为特征,是影响接受胸部放疗的癌症患者的严重疾病。不幸的是,缺乏对RIHD的临床干预措施.硒(Se)是一种微量元素,具有优异的抗氧化和免疫调节性能。然而,其在心脏辐射防护中的应用仍然具有挑战性。在这里,我们开发了一种新型的生物活性蛹虫草基硒口服给药系统(Se@CM),通过抑制过量的ROS产生,在体外对X射线诱导的H9C2细胞损伤表现出优异的辐射防护作用,与辐射防护剂氨磷汀相比。此外,Se@CM在体内对X射线照射表现出出色的心脏保护作用,通过平衡氧化还原平衡和调节Mn-SOD和MDA的表达来减轻心脏功能障碍和心肌纤维化。此外,Se@CM维持免疫稳态,如辐射后通过调节硒蛋白表达上调的T细胞和M2巨噬细胞群体所证明的。一起,这些结果突出了Se@CM的显着抗氧化和免疫调节特性,并阐明了其在IR引起的疾病的心脏保护中的有希望的应用。这项研究为制定预防和管理RIHD的有效策略提供了宝贵的见解。
    Radiation-induced heart disease (RIHD), characterized by severe oxidative stress and immune dysregulation, is a serious condition affecting cancer patients undergoing thoracic radiation. Unfortunately, clinical interventions for RIHD are lacking. Selenium (Se) is a trace element with excellent antioxidant and immune-modulatory properties. However, its application in heart radioprotection remains challenging. Herein, we developed a novel bioactive Cordyceps militaris-based Se oral delivery system (Se@CM), which demonstrated superior radioprotection effects in vitro against X-ray-induced damage in H9C2 cells through suppressing excessive ROS generation, compared to the radioprotectant Amifostine. Moreover, Se@CM exhibited exceptional cardioprotective effects in vivo against X-ray irradiation, reducing cardiac dysfunction and myocardial fibrosis by balancing the redox equilibrium and modulating the expression of Mn-SOD and MDA. Additionally, Se@CM maintained immuno-homeostasis, as evidenced by the upregulated population of T cells and M2 macrophages through modulation of selenoprotein expression after irradiation. Together, these results highlight the remarkable antioxidant and immunity modulation properties of Se@CM and shed light on its promising application for cardiac protection against IR-induced disease. This research provides valuable insights into developing effective strategies for preventing and managing RIHD.
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  • 文章类型: Journal Article
    心脏骤停是各种心脏手术中至关重要的过程,在此期间心脏处于缺血状态。由于主动脉阻塞和开放,缺血/再灌注(I/R)损伤的发生是不可避免的。组氨酸-色氨酸-酮戊二酸(HTK)溶液通常用作器官保护液体以减轻心脏手术期间的心脏损伤。尽管它广泛使用,有显著的潜力,以提高其保护效力。
    使用分离的Langendorff灌注的小鼠心脏模型评估有和没有褪黑激素的HTK溶液的心脏保护作用。将分离的C57bL/6小鼠心脏随机分为四组:对照组,I/R,再灌注前的HTK溶液处理(HTK+I/R),再灌注前HTK溶液联合褪黑素(HTK+M+I/R)。然后测量心功能和心肌损伤标志物。使用AMP激活的蛋白激酶α2(AMPKα2)KO小鼠来研究其潜在机制。
    在我们的研究中,我们发现褪黑激素在离体的Langendorff灌注小鼠模型中显著改善HTK溶液的保护作用,通过减少线粒体损伤,改善能量代谢,抑制心肌细胞凋亡,减少心肌梗死面积。我们还观察到,HTK溶液单独抑制内质网应激是无效的,但是当添加褪黑激素时,ER应激显著减少.此外,发现褪黑素可以减轻心脏I/R期间的羰基应激。有趣的是,我们的结果表明,褪黑素的心脏保护特性依赖于AMPKα2。
    本研究的结果为制定围手术期心脏保护策略提供了有价值的经验基础。
    UNASSIGNED: Cardiac arrest is a crucial procedure in various cardiac surgeries, during which the heart is subjected to an ischemic state. The occurrence of ischemia/reperfusion (I/R) injury is inevitable due to aortic blockage and opening. The Histidine-tryptophan-ketoglutarate (HTK) solution is commonly used as an organ protection liquid to mitigate cardiac injury during cardiac surgery. Despite its widespread use, there is significant potential for improving its protective efficacy.
    UNASSIGNED: The cardioprotective effect of HTK solution with and without melatonin was evaluated using the isolated Langendorff-perfused mouse heart model. The isolated C57bL/6 mouse hearts were randomly divided into four groups: control, I/R, HTK solution treatment before reperfusion (HTK+I/R), and HTK solution combined with melatonin before reperfusion (HTK+M+I/R). Cardiac function and myocardial injury markers were then measured. AMP-activated protein kinase α2 (AMPKα2) KO mice were used to investigate the underlying mechanism.
    UNASSIGNED: In our study, we found that melatonin significantly improved the protective effects of HTK solution in an isolated Langendorff-perfused mouse model, mechanistically by reducing mitochondrial damage, improving energy metabolism, inhibiting cardiomyocyte apoptosis, and reducing myocardial infarction size. We also observed that the HTK solution alone was ineffective in inhibiting ER stress, but when melatonin was added, there was a significant reduction in ER stress. Furthermore, melatonin was found to alleviate carbonyl stress during cardiac I/R. Interestingly, our results showed that the cardioprotective properties of melatonin were dependent on AMPKα2.
    UNASSIGNED: The findings presented in this study offer a valuable empirical foundation for the development of perioperative cardioprotective strategies.
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  • 文章类型: Journal Article
    Catalpol,从地黄中分离出的环烯醚萜类葡萄糖苷,由于其在治疗心脑血管疾病(CVDs)中的潜在用途而受到关注。这篇广泛的综述深入研究了最近对catalpol与各种CVD相关的保护特性的研究,比如动脉粥样硬化,心肌缺血,梗塞,心脏肥大,和心力衰竭。该评论还探讨了该化合物的抗氧化剂,抗炎,和抗凋亡特性,强调重要信号通路的作用,包括PGC-1α/TERT,PI3K/Akt,AMPK,Nrf2/HO-1,雌激素受体(ER),Nox4/NF-κB,和GRP78/PERK。本文讨论了关于catalpol缓解糖尿病心血管并发症能力的新发现,血栓形成,和其他心血管相关疾病。尽管专门针对catalpol对CVD影响的临床研究很少,该化合物已确立的安全性和良好的耐受性表明,它可能是CVD患者的一种有价值的治疗选择.对catalpol和相关的环烯醚萜类衍生物的进一步研究可能会为设计自然和有效的CVD疗法提供新的机会。
    Catalpol, an iridoid glucoside isolated from Rehmannia glutinosa, has gained attention due to its potential use in treating cardio-cerebrovascular diseases (CVDs). This extensive review delves into recent studies on catalpol\'s protective properties in relation to various CVDs, such as atherosclerosis, myocardial ischemia, infarction, cardiac hypertrophy, and heart failure. The review also explores the compound\'s anti-oxidant, anti-inflammatory, and anti-apoptotic characteristics, emphasizing the role of vital signaling pathways, including PGC-1α/TERT, PI3K/Akt, AMPK, Nrf2/HO-1, estrogen receptor (ER), Nox4/NF-κB, and GRP78/PERK. The article discusses emerging findings on catalpol\'s ability to alleviate diabetic cardiovascular complications, thrombosis, and other cardiovascular-related conditions. Although clinical studies specifically addressing catalpol\'s impact on CVDs are scarce, the compound\'s established safety and well-tolerated nature suggest that it could be a valuable treatment alternative for CVD patients. Further investigation into catalpol and related iridoid derivatives may unveil new opportunities for devising natural and efficacious CVD therapies.
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  • 文章类型: Journal Article
    接受术后放射治疗(PRT)的左侧乳腺癌(BC)患者可能有更高的晚期心血管毒性风险,这可以通过保留炉膛的RT技术来减少。这项研究评估了深吸气屏气(DIBH)与自由呼吸(FB)RT相比的剂量学参数。我们分析了影响心脏和心脏亚结构剂量的因素,并寻找了允许患者选择DIBH的解剖因素。
    研究组包括67例左侧BC患者,他们在保乳手术或乳房切除术后接受了RT。接受DIBH治疗的患者接受了屏住呼吸的训练。对FB和DIBH患者均进行了计算机断层扫描(CT)扫描。使用三维(3D)适形RT生成计划。剂量测定变量是从剂量-体积直方图获得的,解剖变量来自CT扫描。两组变量比较采用t检验,U测试,和卡方检验。采用Pearson相关系数进行相关分析。接收器工作特征曲线用于分析预测因子的功效。
    与FB相比,DIBH允许心脏的平均剂量减少,左冠状动脉前降支(LAD),左心室(LV),右心室(RV)减少30.0%,38.7%,39.3%,和34.7%,分别。DIBH显著增加心脏高度(HH),心脏胸壁距离(HCVD),同侧肺和乳腺之间的平均距离(DBIB),心胸壁长度(HCVL)降低(P<0.05)。不同的HH值,DBIB,HCVL,DIBH和FB之间的HCWD分别为1.31、1.95、-0.67和0.22cm,(均P<0.05)。ΔHH是心脏平均剂量的独立预测因子,LAD,LV,和RV,曲线下面积值分别为0.818、0.725、0.821和0.820。
    DIBH显着降低了接受术后RT的左侧BC患者的整个心脏及其亚结构的剂量。ΔHH预测心脏及其亚结构的平均剂量。这些结果可以告知患者选择DIBH。
    UNASSIGNED: Left-sided breast cancer (BC) patients undergoing post-operative radiation therapy (PRT) may have higher risk of late cardiovascular toxicity, which may be reduced by hearth-sparing RT techniques. This study evaluated dosimetric parameters of the deep inspiration breath hold (DIBH) compared to free breathing (FB) RT. We analysed factors impacting on doses to the heart and cardiac substructures and sought anatomic factors allowing patient selection for DIBH.
    UNASSIGNED: The study group included 67 left-sided BC patients who underwent RT after breast-conserving surgery or mastectomy. Patients treated with DIBH were trained to hold their breath. Computed tomography (CT) scans were performed in both FB and DIBH patients. Plans were generated using 3-dimensional (3D) conformal RT. The dosimetric variables were obtained from dose-volume histograms, and the anatomical variables were derived from the CT scans. The variables in the two groups were compared by t-test, the U test, and the chi-squared test. Correlation analysis was performed using Pearson\'s correlation coefficient. Receiver operating characteristic curves were used to analyze the efficacy of the predictors.
    UNASSIGNED: Compared to the FB, DIBH allowed for a mean dose reduction to the heart, left anterior descending coronary artery (LAD), left ventricle (LV), and right ventricle (RV) by 30.0%, 38.7%, 39.3%, and 34.7%, respectively. DIBH markedly increased the heart height (HH), heart chest wall distance (HCWD), the mean distance between the ipsilateral lung and breast (DBIB), and decreased the heart-chest wall length (HCWL) (P<0.05). The different value of HH, DBIB, HCWL, and HCWD between DIBH and FB were 1.31, 1.95, -0.67, and 0.22 cm, respectively (all P<0.05). ΔHH was an independent predictor of the mean dose to the heart, LAD, LV, and RV, with the area under the curve values of 0.818, 0.725, 0.821, and 0.820, respectively.
    UNASSIGNED: DIBH significantly reduced the dose to the entire heart and its substructures in left-sided BC patients undergoing post-operative RT. ΔHH predicts the mean dose to the heart and its substructures. These results may inform patient selection for DIBH.
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  • 文章类型: Review
    未经授权:虎杖。等Zucc(Polysho科),其根源包含在《中国药典》中,名称为“虎章”,作为药用植物和蔬菜有着悠久的历史。虎杖已在中药中用于治疗炎症,高脂血症,等。
    UASSIGNED:本文综述了虎杖及其提取物的药理作用和临床应用,无论是体内还是体外。同时对虎杖及其提取物的主要植物化学成分和药动学进行了综述。
    未经评估:这些数据是从主要的医疗数据库中检索的,例如CNKI,PubMed,和SinoMed,从2014年到2022年。虎杖,药理学,毒性,临床应用,和药代动力学被用作关键词。
    未经批准:根茎,叶子,虎杖和花具有不同的植物化学成分。这种植物含有类黄酮,蒽醌,还有stilbenes.虎杖和提取物具有抗炎作用,抗氧化,抗癌,心脏保护,和其他药理作用。它在诊所用于治疗头晕,头痛,外伤,水和火燃烧。
    未经授权:虎杖具有治疗多种疾病的潜力,比如关节炎,溃疡性结肠炎,哮喘,和心脏肥大.它具有广泛的医疗应用,但主要集中在根药上;它的空中部分应该受到更多的关注。药代动力学也需要进一步研究。
    UNASSIGNED: Polygonum cuspidatum Sieb. et Zucc (Polygonaceae), the root of which is included in the Chinese Pharmcopoeia under the name \'Huzhang\', has a long history as a medicinal plant and vegetable. Polygonum cuspidatum has been used in traditional Chinese medicine for the treatment of inflammation, hyperlipemia, etc.
    UNASSIGNED: This article reviews the pharmacological action and the clinical applications of Polygonum cuspidatum and its extracts, whether in vivo or in vitro. We also summarized the main phytochemical constituents and pharmacokinetics of Polygonum cuspidatum and its extracts.
    UNASSIGNED: The data were retrieved from major medical databases, such as CNKI, PubMed, and SinoMed, from 2014 to 2022. Polygonum cuspidatum, pharmacology, toxicity, clinical application, and pharmacokinetics were used as keywords.
    UNASSIGNED: The rhizomes, leaves, and flowers of Polygonum cuspidatum have different phytochemical constituents. The plant contains flavonoids, anthraquinones, and stilbenes. Polygonum cuspidatum and the extracts have anti-inflammatory, antioxidation, anticancer, heart protection, and other pharmacological effects. It is used in the clinics to treat dizziness, headaches, traumatic injuries, and water and fire burns.
    UNASSIGNED: Polygonum cuspidatum has the potential to treat many diseases, such as arthritis, ulcerative colitis, asthma, and cardiac hypertrophy. It has a broad range of medicinal applications, but mainly focused on root medication; its aerial parts should receive more attention. Pharmacokinetics also need to be further investigated.
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  • 文章类型: Journal Article
    BACKGROUND: Studying the clinical utility of deep-inspirational breath-hold (DIBH) in left breast cancer radiotherapy (RT) was aimed at focusing on dosimetry and feasibility aspects.
    METHODS: In this prospective trial all enrolled patients went through planning CT in supine position under both DIBH and free breathing (FB); in whole breast irradiation (WBI) cases prone CT was also taken. In 3-dimensional conformal radiotherapy (3DCRT) plans heart, left anterior descending coronary artery (LAD), ipsilateral lung and contralateral breast doses were analyzed. The acceptance of DIBH technique as reported by the patients and the staff was analyzed; post-RT side-effects including radiation lung changes (visual scores and lung density measurements) were collected.
    RESULTS: Among 130 enrolled patients 26 were not suitable for the technique while in 16, heart or LAD dose constraints were not met in the DIBH plans. Among 54 and 34 patients receiving WBI and postmastectomy/nodal RT, respectively with DIBH, mean heart dose (MHD) was reduced to < 50%, the heart V25 Gy to < 20%, the LAD mean dose to < 40% and the LAD maximum dose to about 50% as compared to that under FB; the magnitude of benefit was related to the relative increase of the ipsilateral lung volume at DIBH. Nevertheless, heart and LAD dose differences (DIBH vs. FB) individually varied. Among the WBI cases at least one heart/LAD dose parameter was more favorable in the prone or in the supine FB plan in 15 and 4 cases, respectively; differences were numerically small. All DIBH patients completed the RT, inter-fraction repositioning accuracy and radiation side-effects were similar to that of other breast RT techniques. Both the patients and radiographers were satisfied with the technique.
    CONCLUSIONS: DIBH is an excellent heart sparing technique in breast RT, but about one-third of the patients do not benefit from that otherwise laborious procedure or benefit less than from an alternative method.
    BACKGROUND: retrospectively registered under ISRCTN14360721 (February 12, 2021).
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  • 文章类型: Journal Article
    Our aim was to investigate if the cardioplegic solution HTK can be improved by the addition of the ROS scavenger melatonin. 158 guinea pig hearts without (UI80) or with HTK protection (HTK80) were investigated in ischemia/reperfusion experiments. Ischemia lasted 80 min at 30 °C. Melatonin was given before ischemia (UI80 + M1, HTK80 + M1) or before and after ischemia (UI80 + M2, HTK80 + M2). We measured the left ventricular developed pressure (LVDP), diastolic pressure (LVPmin), cardiac rhythm (VC-RR), time of electrical cell uncoupling (t-in) and recovery (t-ret), intracellular Ca++ [Ca++], and postischemic ROS. After 45 min reperfusion, LVDP in UI80 was significantly higher than in HTK80 (p < .01). Compared to UI80, the postischemic ROS burst was slightly smaller in HTK80 and significantly smaller in HTK80 + M1 and HTK80 + M2 (p < .05). Melatonin had no effect on LVPmin, t-in, t-ret, [Ca++], and on LVDP in groups UI80 + M1 and HTK80 + M1, improved slightly VC-RR (n. s.) but significantly decreased LVDP in the groups UI80 + M2 and HTK80 + M2 (p < .01). With melatonin we were able to attenuate the postischemic ROS burst, but the tissue damage by ROS seemed to be less important for the chosen ischemia condition because melatonin was unable to improve the functional recovery during reperfusion of HTK protected hearts.
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  • 文章类型: Comparative Study
    We investigated isolated guinea pig hearts (n = 121) in an ischemia/ reperfusion model with the aim to compare the efficiency of the cardioplegic solution HTK with its novel replacement HTKN. Following consolidation with Tyrode\'s solution, ischemia started either immediately or after preceding cardioplegia with HTK, HTKN, or modified HTK enriched with Ca. Ischemia lasted either 80 min at 30 °C, or 360 min at 5 °C, or 81 min at 30 °C with intermittent cardioplegic perfusion. During ischemia we measured intracellular calcium (iCa++) and the time of gap junction uncoupling (t-in). During reperfusion we measured the reestablishment of cell coupling (t-ret), left ventricular developed pressure (LVDP), and heart rhythm (VC-RR). In 5 °C groups, iCa++ at t-in was significantly higher than before ischemia, and longest t-in, shortest t-ret, and best VC-RR were observed after HTK-protection. Of all 30 °C groups, the intermittent group with modified HTK showed shortest t-ret, best VC-RR, and the highest LVDP. At 5 °C, HTK groups had higher LVDP than HTK-N groups, but not at 30 °C. The data suggest that the higher calcium level in the HTK-N solution improves reperfusion after short ischemia at 30 °C but for long lasting ischemia at 5 °C it is beneficial to use the HTK solution.
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  • 文章类型: Journal Article
    The benefit of reduced radiation heart exposure in the prone vs. supine position individually differs. In this prospective cohort study, the goal was to develop a simple method for the operation of a validated model for the prediction of preferable treatment position during left breast radiotherapy.
    In 100 cases, a single CT slice was utilized for the collection of the needed patient-specific data (in addition to body mass index, the distance of the LAD from the chest wall and the area of the heart included in the radiation fields at the middle of the heart in the supine position). Outcome was analyzed in relation to the full CT series acquired in both positions and dosimetric data.
    Great consistency was found between the tested and original method regarding sensitivity and specificity. The prioritization of LAD dose, and the use of heart dose and position-specific dose constraints as safety measures ensure sensitivity and specificity values of 82.8% and 87.3%, respectively. In an additional \"routine clinical practice\" series of 60 patients the new method seemed feasible in routine clinical practice. External testing on a 28-case series indicated similar accuracy.
    We consider this simple clinical tool appropriate for assisting individual positioning aiming at maximum heart protection during left breast irradiation.
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