Relationship between mitochondrial respiratory dysfunction of blood mononuclear cells and heart failure severity

Chronic heart failure(CHF)is a clinical syndrome manifested by reduced pumping ability of the heart,increased pressure in heart chambers in both physical activity and at rest.The symptoms of this syndrome are dyspnea,undue fatigability,peripheral edema,which follow structural and functional changes of the myocardium.[1]The growing incidence of CHF,especially among elderly people,is an urgent problem for medicine in the vast majority of industrialized countries.For instance,in Russian Federation,CHF is diagnosed in about 7%of cardiovascular patients.At the same time,this indicator varies from 0.3%in young people(20-29 years old)to 70%in the older age group.[2,3].

A historical literature review of coronary microvascular obstruction and intra-myocardial hemorrhage as functional/structural phenomena

The analysis of experimental data demonstrates that platelets and neutrophils are involved in the no-reflow phenomenon,also known as microvascular obstruction(MVO).However,studies performed in the isolated perfused hearts subjected to ischemia/reperfusion(I/R)do not suggest the involvement of microembolization and microthrombi in this phenomenon.The intracoronary administration of alteplase has been found to have no effect on the occurrence of MVO in patients with acute myocardial infarction.Consequently,the major events preceding the appearance of MVO in coronary arteries are independent of microthrombi,platelets,and neutrophils.Endothelial cells appear to be the target where ischemia can disrupt the endothelium-dependent vasodilation of coronary arteries.However,reperfusion triggers more pronounced damage,possibly mediated by pyroptosis.MVO and intra-myocardial hemorrhage contribute to the adverse post-infarction myocardial remodeling.Therefore,pharmacological agents used to treat MVO should prevent endothelial injury and induce relaxation of smooth muscles.Ischemic conditioning protocols have been shown to prevent MVO,with L-type Ca2+channel blockers appearing the most effective in treating MVO.

Do reactive oxygen species damage or protect the heart in ischemia and reperfusion?Analysis on experimental and clinical data

The role of reactive oxygen species(ROS)in ischemic and reperfusion(I/R)injury of the heart has been discussed for more than 40 years.It has been demonstrated that reperfusion triggers a multiple increase in free radical generation in the isolated heart.Antioxidants were found to have the ability to mitigate I/R injury of the heart.However,it is unclear whether their cardioprotective effect truly depends on the decrease of ROS levels in myocardial tissues.Since high doses and high concentrations of antioxidants were experimentally used,it is highly likely that the cardioprotective effect of antioxidants depends on their interaction not only with free radicals but also with other molecules.It has been demonstrated that the antioxidant N-2-mercaptopropionyl glycine or NDPH oxidase knockout abolished the cardioprotective effect of ischemic preconditioning.Consequently,there is evidence that ROS protect the heart against the I/R injury.

The effect of an adaptation to hypoxia on cardiac tolerance to ischemia/reperfusion

The acute myocardial infarction(AMI)and sudden cardiac death(SCD),both associated with acute cardiac ischemia,are one of the leading causes of adult death in economically developed countries.The development of new approaches for the treatment and prevention of AMI and SCD remains the highest priority for medicine.A study on the cardiovascular effects of chronic hypoxia(CH)may contribute to the development of these methods.Chronic hypoxia exerts both positive and adverse effects.The positive effects are the infarct-reducing,vasoprotective,and antiarrhythmic effects,which can lead to the improvement of cardiac contractility in reperfusion.The adverse effects are pulmonary hypertension and right ventricular hypertrophy.This review presents a comprehensive overview of how CH enhances cardiac tolerance to ischemia/reperfusion.It is an in-depth analysis of the published data on the underlying mechanisms,which can lead to future development of the cardioprotective effect of CH.A better understanding of the CH-activated protective signaling pathways may contribute to new therapeutic approaches in an increase of cardiac tolerance to ischemia/reperfusion.

Antagonism of estrogen-mediated cell proliferation by raloxifene in prevention of ageing-related prostatic hyperplasia

雌激素在良性的 prostatic 增生(BPH ) 的开始和发展有重要角色。雌激素受体的管理者(嗯) 织物特定、房间特定。我们评估了雌激素对手的效果， raloxifene (Ral ) ，在由在二不同前列腺的增长上调查它的效果的 BPH 的预防和治疗上，房间排队：一根 stromal 房间线， WPMY-1，和良性的 prostatic 增生上皮的房间线， BPH-1。我们另外在雌激素和雄激素在一个老鼠模型导致的 prostatic 增生上评估了它的效果。prostatic 增生的预防上的 Ral 的效果被 haematoxylin 并且曙红为原子抗原和伪 - 弄平的增殖的房间染色和量的 immunohistochemistry (IHC ) 分析肌肉肌动朊。在 vitro 并且在 vivo， tamoxifen (Tam ) ，另一反雌激素药，和 finasteride (鳍) ，为 BPH 的临床的处理的药，用作功效控制。在里面 vitro 数据证明既不 Ral 也不 Tam 独自既不影响了 WPMY-1 的增长， BPH-1，而是两个在支持二个房间的增长反对了 oestradiol 的效果。从老鼠前列腺染色的 IHC 的结果显示了那，类似于 Tam 和鳍， Ral 在 vivo 禁止了 stromal 房间的增长。与 Tam 相对照，有趣地， Ral 和鳍禁止了上皮的房间的增长。Furthemore， Ral 治疗强烈很减少了 prostatic acini 的数字和光滑的肌肉房间的包围的层比鳍(P < 0.05 ) 。我们的数据第一次证明 Ral 可以在对的老鼠前列腺的反应有一个角色选择嗯调节的人。

Pyroptosis is a drug target for prevention of adverse cardiac remodeling: The crosstalk between pyroptosis, apoptosis, and autophagy

Acute myocardial infarction(AMI)is one of the main reasons of cardiovascular disease-related death.The introduction of percutaneous coronary intervention to clinical practice dramatically decreased the mortality rate in AMI.Adverse cardiac remodeling is a serious problem in cardiology.An increase in the effectiveness of AMI treatment and prevention of adverse cardiac remodeling is difficult to achieve without understanding the mechanisms of reperfusion cardiac injury and cardiac remodeling.Inhibition of pyroptosis prevents the development of postinfarction and pressure overload-induced cardiac remodeling,and mitigates cardiomyopathy induced by diabetes and metabolic syndrome.Therefore,it is reasonable to hypothesize that the pyroptosis inhibitors may find a role in clinical practice for treatment of AMI and prevention of cardiac remodeling,diabetes and metabolic syndrome-triggered cardiomyopathy.It was demonstrated that pyroptosis interacts closely with apoptosis and autophagy.Pyroptosis could be inhibited by nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 inhibitors,caspase-1 inhibitors,microRNA,angiotensin-converting enzyme inhibitors,angiotensinⅡreceptor blockers,and traditional Chinese herbal medicines.

Ginkgo Biloba Extract for Angina Pectoris:A Systematic Review

Objective:To evaluate the efficacy and safety of Ginkgo Biloba extract for,patients with angina pectoris according to the available evidence.Methods:Electronic databases were searched for all of the randomized controlled trials(RCTs) of angina pectoris treatments with Ginkgo Biloba extract,either alone or combined with routine Western medicine(RWM),and controlled by untreated,placebo,Chinese patent medicine,or RWM treatment.The RCTs were retrieved from the following electronic databases:PubMed/MEDLINE,ProQuest Health and Medical Complete,Springer,Elsevier,and ProQuest Dissertations and Theses,Wanfang Data,China National Knowledge Infrastructure(CNKI),VIP database,China Biology Medicine(CBM),Chinese Medical Citation Index(CMCI),from the earliest database records to December2012.No language restriction was applied.Study selection,data extraction,quality assessment,and data analyses were conducted according to the Cochrane standards.RevMan 5.1.0 provided by Cochrane Collaboration The data were analysed by using.Results:A total of 23 RCTs(involving 2,529 patients) were included and the methodological quality was evaluated as generally low.Ginkgo Biloba extract with RWM was more effective in angina relief and electrocardiogram improvement than RWM alone.Reported adverse events included epigastric discomfort,nausea,gastrointestinal reaction,and bitter taste.Conclusions:Ginkgo Biloba extract may have beneficial effects on patients with angina pectoris,although the low quality of existing trials makes it difficult to draw a satisfactory conclusion.More rigorous,high quality clinical trials are needed to provide conclusive evidence.

Yang-tonifying traditional Chinese medicinal plants and their potential phytoandrogenic activity

The concept of phytoandrogens, plants that contain androgens or those that stimulate androgenic activity in men, is relatively new. In traditional Chinese medicine a number of phytoandrogens are classified in medicinal plant restoratives for reinforcing yang, and they find their application in the treatment of the kidney yang deficiency diseases. In this review, the phytoandrogens used in traditional Chinese medicine are listed, and their proven applications in the treatment of kidney yang deficiency diseases, such as sexual disorders, cancer, and obesity and associated metabolic syndromes are presented. As a background, the mechanism of action of androgens, their synthesis and metabolism, the interrelations of androgens and estrogens, as well as the state of art methods to detect and analyze these hormonal activities in medicinal plants are discussed.

Bidirectional regulation of angiogenesis by phytoestrogens through estrogen receptor-mediated signaling networks

Sex hormone estrogen is one of the most active intrinsic angiogenesis regulators; its therapeutic use has been limited due to its carcinogenic potential. Plant-derived phytoestrogens are attractive alternatives, but reports on their angiogenic activities often lack in-depth analysis and sometimes are controversial. Herein, we report a data-mining study with the existing literature, using IPA system to classify and characterize phytoestrogens based on their angiogenic properties and pharmacological consequences. We found that pro-angiogenic phytoestrogens functioned predominantly as cardiovascular protectors whereas anti-angiogenic phytoestrogens played a role in cancer prevention and therapy. This bidirectional regulation were shown to be target-selective and, for the most part, estrogen-receptor-dependent. The transactivation properties of ERα and ERβ by phytoestrogens were examined in the context of angiogenesis-related gene transcription. ERα and ERβ were shown to signal in opposite ways when complexed with the phytoestrogen for bidirectional regulation of angiogenesis. With ERα, phytoestrogen activated or inhibited transcription of some angiogenesis-related genes, resulting in the promotion of angiogenesis, whereas, with ERβ, phytoestrogen regulated transcription of angiogenesis-related genes, resulting in inhibition of angiogenesis. Therefore, the selectivity of phytoestrogen to ERα and ERβ may be critical in the balance of pro- or anti-angiogenesis process.