Conditioning medicine最新文献

{"title":"Mitochondrial shaping proteins as novel treatment targets for cardiomyopathies.","authors":"Siavash Beikoghli Kalkhoran,&nbsp;Sauri Hernandez-Resendiz,&nbsp;Sang-Ging Ong,&nbsp;Chrishan J A Ramachandra,&nbsp;Derek J Hausenloy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Heart failure (HF) is one of the leading causes of death and disability worldwide. The prevalence of HF continues to rise, and its outcomes are worsened by risk factors such as age, diabetes, obesity, hypertension, and ischemic heart disease. Hence, there is an unmet need to identify novel treatment targets that can prevent the development and progression of HF in order to improve patient outcomes. In this regard, cardiac mitochondria play an essential role in generating the ATP required to maintain normal cardiac contractile function. Mitochondrial dysfunction is known to contribute to the pathogenesis of a number of cardiomyopathies including those secondary to diabetes, pressure-overload left ventricular hypertrophy (LVH), and doxorubicin cardiotoxicity. Mitochondria continually change their shape by undergoing fusion and fission, and an imbalance in mitochondrial fusion and fission have been shown to impact on mitochondrial function, and contribute to the pathogenesis of these cardiomyopathies. In this review article, we focus on the role of mitochondrial shaping proteins as contributors to the development of three cardiomyopathies, and highlight their therapeutic potential as novel treatment targets for preventing the onset and progression of HF.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"3 4","pages":"216-226"},"PeriodicalIF":0.0,"publicationDate":"2020-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595308/pdf/nihms-1631830.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38562090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms underlying diabetic cardiomyopathy: From pathophysiology to novel therapeutic targets.","authors":"Shuo Cong,&nbsp;Chrishan J A Ramachandra,&nbsp;Kp Myu Mai Ja,&nbsp;Jonathan Yap,&nbsp;Winston Shim,&nbsp;Lai Wei,&nbsp;Derek J Hausenloy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DC) is defined as a clinical condition of cardiac dysfunction that occurs in the absence of coronary atherosclerosis, valvular disease, and hypertension in patients with diabetes mellitus (DM). Despite the increasing worldwide prevalence of DC, due to the global epidemic of DM, the underlying pathophysiology of DC has not been fully elucidated. In addition, the clinical criteria for diagnosing DC have not been established, and specific therapeutic options are not currently available. The current paradigm suggests the impaired cardiomyocyte function arises due to a number of DM-related metabolic disturbances including hyperglycemia, hyperinsulinemia, and hyperlipidemia, which lead to diastolic dysfunction and signs and symptoms of heart failure. Other factors, which have been implicated in the progression of DC, include mitochondrial dysfunction, increased oxidative stress, impaired calcium handling, inflammation, and cardiomyocyte apoptosis. Herein, we review the current theories surrounding the occurrence and progression of DC, and discuss the recent advances in diagnostic methodologies and therapeutic strategies. Moreover, apart from conventional animal DC models, we highlight alternative disease models for studying DC such as the use of patient-derived human induced pluripotent stem cells (hiPSCs) for studying the mechanisms underlying DC. The ability to obtain hiPSC-derived cardiomyocytes from DM patients with a DC phenotype could help identify novel therapeutic targets for preventing and delaying the progression of DC, and for improving clinical outcomes in DM patients.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"3 2","pages":"82-97"},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221238/pdf/nihms-1593381.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39104090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ischemic postconditioning for stroke treatment: current experimental advances and future directions.","authors":"Hansen Chen,&nbsp;Jiangang Shen,&nbsp;Heng Zhao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Ischemic postconditioning (IPostC) protects against brain injury induced by stroke and is a potential strategy for ischemic stroke treatment. Understanding its underlying mechanisms and potential hurdles is essential for clinical translation. In this review article, we will summarize the current advances in IPostC for stroke treatment and the underlying protective mechanisms. Strong evidence suggests that IPostC reduces brain infarct size, attenuates blood-brain barrier (BBB) damage and brain edema, and improves neurological outcomes. IPostC also promotes neurogenesis and angiogenesis at the recovery phase of ischemic stroke. The protective mechanisms involve its effects on anti-oxidative stress, anti-inflammation, and anti-apoptosis. In addition, it regulates neurotransmitter receptors, ion channels, heat shock proteins (HSP) 40/70, as well as growth factors such as BDNF and VEGF. Furthermore, IPostC modulates several cell signaling pathways, including the PI3K/Akt, MAPK, NF-κB, and the Gluk2/PSD95/MLK3/MKK7/JNK3 pathways. We also discuss the potential hurdles for IPostC's clinical translation, including insufficient IPostC algorithm studies, such as therapeutic time windows and ischemia-reperfusion periods and cycles, as well as its long-term protection. In addition, future studies should address confounding factors such as age, sex, and pre-existing conditions such as hypertension and hyperglycemia before stroke onset. At last, the combination of IPostC with other treatments, such as tissue plasminogen activator (t-PA), merits further exploration.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"3 2","pages":"104-115"},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360401/pdf/nihms-1593305.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39314389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mechanisms of Intermittent Fasting-induced Ischemic Tolerance.","authors":"Raghu Vemuganti,&nbsp;Thiruma V Arumugam","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Diet is a significant factor in determining human well-being. Excessive eating and/or diets with higher than needed amounts of carbohydrates, salt, and fat are known to cause metabolic disorders and functional changes in the body. To compensate the ill effects, many designer diets including the Mediterranean diet, the Okinawa diet, vegetarian/vegan diets, keto diet, anti-inflammatory diet, and the anti-oxidant diet have been introduced in the past 2 decades. While these diets are either enriched or devoid of one or more specific components, a better way to control diet is to limit the amount of food consumed. Caloric restriction (CR), which involves limiting the amount of food consumed rather than eliminating any specific type of food, as well as intermittent fasting (IF), which entails limiting the time during which food can be consumed on a given day, have gained popularity because of their positive effects on human health. While the molecular mechanisms of these 2 dietary regimens have not been fully deciphered, they are known to prolong the life span, control blood pressure, and blood glucose levels. Furthermore, CR and IF were both shown to decrease the incidence of heart attack and stroke, as well as their ill effects. In particular, IF is thought to promote metabolic switching by altering gene expression profiles leading to reduced inflammation and oxidative stress, while increasing plasticity and regeneration.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"3 1","pages":"9-17"},"PeriodicalIF":0.0,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281895/pdf/nihms-1594284.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39200404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticle delivery of cardioprotective therapies.","authors":"Abraham Mendez-Fernandez,&nbsp;Hector A Cabrera-Fuentes,&nbsp;Bhaarathy Velmurugan,&nbsp;Jason Irei,&nbsp;William A Boisvert,&nbsp;Shengjie Lu,&nbsp;Derek J Hausenloy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Acute myocardial infarction (AMI), and the heart failure (HF) that often follows, are leading causes of death and disability worldwide. Crucially, there are currently no effective treatments, other than myocardial reperfusion, for reducing myocardial infarct (MI) size and preventing HF following AMI. Thus, there is an unmet need to discover novel cardioprotective therapies to reduce MI size, and prevent HF in AMI patients. Although a large number of therapies have been shown to reduce MI size in experimental studies, the majority have failed to benefit AMI patients. Failure to deliver cardioprotective therapy to the ischemic heart in sufficient concentrations following AMI is a major factor for the lack of success observed in previous clinical cardioprotection studies. Therefore, new strategies are needed to improve the delivery of cardioprotective therapies to the ischemic heart following AMI. In this regard, nanoparticles have emerged as drug delivery systems for improving the bioavailability, delivery, and release of cardioprotective therapies, and should result in improved efficacy in terms of reducing MI size and preventing HF. In this article, we provide a review of currently available nanoparticles, some of which have been FDA-approved, in terms of their use as drug delivery systems in cardiovascular disease and cardioprotection.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"3 1","pages":"18-30"},"PeriodicalIF":0.0,"publicationDate":"2020-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279025/pdf/nihms-1574142.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39189869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary Restriction and Epigenetics: Part I.","authors":"Gavin Yong-Quan Ng, David Yang-Wei Fann, Dong-Gyu Jo, Christopher G Sobey, Thiruma V Arumugam","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Biological aging occurs concomitantly with chronological aging and is commonly burdened by the development of age-related conditions, such as neurodegenerative, cardiovascular, and a myriad of metabolic diseases. With a current global shift in disease epidemiology associated with aging and the resultant social, economic, and healthcare burdens faced by many countries, the need to achieve successful aging has fueled efforts to address this problem. Aging is a complex biological phenomenon that has confounded much of the historical research effort to understand it, with still limited knowledge of the underlying molecular mechanisms. Interestingly, dietary restriction (DR) is one intervention that produces anti-aging effects from simple organisms to mammals. Research into DR has revealed robust systemic effects that can result in attenuation of age-related diseases via a myriad of molecular mechanisms. Given that numerous age-associated diseases are often polygenic and affect individuals differently, it is possible that they are confounded by interactions between environmental influences and the genome, a process termed 'epigenetics'. In part one of the review, we summarize the different variants of DR regimens and their corresponding mechanism(s) and resultant effects, as well as in-depth analysis of current knowledge of the epigenetic landscape.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"2 6","pages":"284-299"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007115/pdf/nihms-1067170.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37627977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Regulation by Dietary Restriction: Part II.","authors":"Gavin Yong-Quan Ng,&nbsp;David Yang-Wei Fann,&nbsp;Dong-Gyu Jo,&nbsp;Christopher G Sobey,&nbsp;Thiruma V Arumugam","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the first part of our review, we extensively discuss the different variants of dietary restriction (DR) regimens, as well as its corresponding mechanism(s) and subsequent effects. We also provide a detailed analysis of the different epigenetic mechanisms based on current knowledge. We postulate that DR may represent an environmental intervention that can modulate the epigenomic profile of an individual. It is highly plausible that epigenetic regulation by DR may help explain the asymmetric manifestation of DR effects in different individuals. Additionally, epigenetic modifications via DR may lead to epigenetic programming, providing protection against age-associated diseases, which in turn could lead to reduced morbidity and increased lifespan. In the second part of the review, we summarize recent findings that highlight the epigenomic axis of DR, which provides a better understanding of the mechanisms by which its numerous health benefits are achieved.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"2 6","pages":"300-310"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007178/pdf/nihms-1067171.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37627976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights provided by myofibril mechanics in inherited cardiomyopathies.","authors":"Ying-Hsi Lin, Jonathan Yap, Chrishan J A Ramachandra, Derek J Hausenloy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cardiomyopathies represent a heterogeneous group of cardiac disorders that perturb cardiac contraction and/or relaxation, and can result in arrhythmias, heart failure, and sudden cardiac death. Based on morphological and functional differences, cardiomyopathies have been classified into hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM). It has been well documented that mutations in genes encoding sarcomeric proteins are associated with the onset of inherited cardiomyopathies. However, correlating patient genotype to the clinical phenotype has been challenging because of the complex genetic backgrounds, environmental influences, and lifestyles of individuals. Thus, \"scaling down\" the focus to the basic contractile unit of heart muscle using isolated single myofibril function techniques is of great importance and may be used to understand the molecular basis of disease-causing sarcomeric mutations. Single myofibril bundles harvested from diseased human or experimental animal hearts, as well as cultured adult cardiomyocytes or human cardiomyocytes derived from induced pluripotent stem cells, can be used, thereby providing an ideal multi-level, cross-species platform to dissect sarcomeric function in cardiomyopathies. Here, we will review the myofibril function technique, and discuss alterations in myofibril mechanics, which are known to occur in sarcomeric genetic mutations linked to inherited HCM, DCM, and RCM, and describe the therapeutic potential for future target identification.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"2 5","pages":"213-224"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055865/pdf/nihms-1561662.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10247168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is there a role for remote ischemic conditioning in preventing 5-fluorouracil-induced coronary vasospasm?","authors":"Jun Chong,&nbsp;Andrew Fw Ho,&nbsp;Jonathan Yap,&nbsp;Heerajnarain Bulluck,&nbsp;Derek J Hausenloy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cardiac ischemia associated with chemotherapy has been linked to several anti-neoplastic agents and is multifactorial in etiology. Coronary artery vasospasm is one of the most commonly reported effects of cancer therapy that can lead to myocardial ischemia or infarction. The chemotherapy agent 5-fluorouracil (5-FU) or its oral pro-drug capecitabine can result in coronary vascular endothelial dysfunction causing coronary artery spasm, and possibly coronary thrombosis. These drugs have also been shown to be associated with myocardial infarction, malignant ventricular arrhythmias, heart failure, cardiogenic shock, and sudden death. The proposed mechanisms underlying cardiotoxicity induced by 5-FU are vascular endothelial damage followed by thrombus formation, ischemia secondary to coronary artery vasospasm, direct toxicity on myocardium, and thrombogenicity. There remains a pressing need to discover novel and effective therapies that can prevent or ameliorate 5-FU associated cardiotoxicity. To this point, promising overlap has been observed between proposed remote ischemic conditioning (RIC) cardioprotective mechanisms and 5FU-associated cardiotoxic cellular pathways. RIC, in which transient episodes of limb ischemia and reperfusion (induced by inflations and deflations of a pneumatic cuff placed on the upper arm or thigh), confer both cardioprotective and vasculoprotective effects, and may therefore prevent 5-FU coronary artery spasm/cardiotoxicity. In this review, we will be discussing the following potentially therapeutic aspects of RIC in ameliorating 5-FU associated cardiotoxicity: sequential phases of 5-FU cardiotoxicity as possible targets for dual windows of cardioprotection characteristic of RIC; protective effects of RIC on endothelial function and microvasculature in relation to 5-FU induced endothelial dysfunction/microvascular dysfunction; reduction in platelet activation by RIC in the context of 5-FU induced thrombogenicity; and the utility of improvement in mitochondrial function conferred by RIC in 5-FU induced cellular toxicity secondary to mitochondrial dysfunction.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":" ","pages":"204-212"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055861/pdf/nihms-1560711.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37706625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Near infrared light amplifies endothelial progenitor cell accumulation after stroke.","authors":"Andrew Vahabzadeh-Hagh,&nbsp;Thomas J McCarthy,&nbsp;Luis De Taboada,&nbsp;Jackson Streeter,&nbsp;Alvaro Pascual-Leone,&nbsp;Eng H Lo,&nbsp;Kazuhide Hayakawa","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Damage-associated molecular pattern signals may play key roles in mediating non-cell autonomous effects of pre and post-conditioning. Here, we show that near-infrared (NIR) light stimulation of astrocytes increases a calcium-dependent secretion of the prototypical DAMP, HMGB1, which may then accelerate endothelial progenitor cell (EPC) accumulation after stroke. Conditioned media from NIR-stimulated astrocytes increased EPC proliferation in vitro, and blockade of HMGB1 with siRNA diminished the effect. In vivo transcranial NIR treatment confirmed that approximately 40% of NIR could penetrate the scalp and skull. Concomitantly, NIR increased GFAP expression in normal mouse brain at 30 min after the irradiation. In a mouse model of focal ischemia, repeated irradiation of NIR at days 5, 9, and 13 successfully increased HMGB1 in peri-infarct cortex, leading to a higher accumulation of EPCs at 14 days post-stroke. Conditioning and tolerance are now known to involve cell-cell signaling between all cell types in the neurovascular unit. Taken together, our proof-of-concept study suggest that NIR light may be an effective conditioning tool to stimulate astrocytic signaling and promote EPC accumulation after stroke.</p>","PeriodicalId":72686,"journal":{"name":"Conditioning medicine","volume":"2 4","pages":"170-177"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291201/pdf/nihms-1621490.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39211133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}