Search

More interestingly from a translational perspective, intrapericardial LNP-TARID therapy also exhibited promising protective effects in infarct repair and fibrosis resolution in a porcine model of myocardial ischaemia-reperfusion. Graph: Graphical Abstract Intrapericardial lncRNA-TARID therapy mitigates myocardial fibrosis. Collectively, LNP-TARID therapy appears to be a promising antifibrotic therapy that acts by targeting EPDC-myofibroblast differentiation. [Extracted from the article]

Acute myocardial infarction (MI) inflicts massive injury to the coronary microcirculation leading to vascular disintegration and capillary rarefication in the infarct region. Tissue repair after MI involves a robust angiogenic response that commences in the infarct border zone and extends into the necrotic infarct core. Technological advances in several areas have provided novel mechanistic understanding of postinfarction angiogenesis and how it may be targeted to improve heart function after MI. Cell lineage tracing studies indicate that new capillary structures arise by sprouting angiogenesis from pre-existing endothelial cells (ECs) in the infarct border zone with no meaningful contribution from non-EC sources. Single-cell RNA sequencing shows that ECs in infarcted hearts may be grouped into clusters with distinct gene expression signatures, likely reflecting functionally distinct cell populations. EC-specific multicolour lineage tracing reveals that EC subsets clonally expand after MI. Expanding EC clones may arise from tissue-resident ECs with stem cell characteristics that have been identified in multiple organs including the heart. Tissue repair after MI involves interactions among multiple cell types which occur, to a large extent, through secreted proteins and their cognate receptors. While we are only beginning to understand the full complexity of this intercellular communication, macrophage and fibroblast populations have emerged as major drivers of the angiogenic response after MI. Animal data support the view that the endogenous angiogenic response after MI can be boosted to reduce scarring and adverse left ventricular remodelling. The improved mechanistic understanding of infarct angiogenesis therefore creates multiple therapeutic opportunities. During preclinical development, all proangiogenic strategies should be tested in animal models that replicate both cardiovascular risk factor(s) and the pharmacotherapy typically prescribed to patients with acute MI. Considering that the majority of patients nowadays do well after MI, clinical translation will require careful selection of patients in need of proangiogenic therapies. [ABSTRACT FROM AUTHOR]

In the high-stakes arena of drug discovery, the journey from bench to bedside is hindered by a daunting 92% failure rate, primarily due to unpredicted toxicities and inadequate therapeutic efficacy in clinical trials. The FDA Modernization Act 2.0 heralds a transformative approach, advocating for the integration of alternative methods to conventional animal testing, including cell-based assays that employ human induced pluripotent stem cell (iPSC)-derived organoids, and organ-on-a-chip technologies, in conjunction with sophisticated artificial intelligence (AI) methodologies. Our review explores the innovative capacity of iPSC-derived clinical trial in a dish models designed for cardiovascular disease research. We also highlight how integrating iPSC technology with AI can accelerate the identification of viable therapeutic candidates, streamline drug screening, and pave the way toward more personalized medicine. Through this, we provide a comprehensive overview of the current landscape and future implications of iPSC and AI applications being navigated by the research community and pharmaceutical industry.

Cardiovascular diseases persist as a global health challenge that requires methodological innovation for effective drug development. Conventional pipelines relying on animal models suffer from high failure rates due to significant interspecies variation between humans and animal models. In response, the recently enacted Food and Drug Administration Modernization Act 2.0 encourages alternative approaches including induced pluripotent stem cells (iPSCs). Human iPSCs provide a patient-specific, precise, and screenable platform for drug testing, paving the way for cardiovascular precision medicine. This review discusses milestones in iPSC differentiation and their applications from disease modelling to drug discovery in cardiovascular medicine. It then explores challenges and emerging opportunities for the implementation of 'clinical trials in-a-dish'. Concluding, this review proposes a framework for future clinical trial design with strategic incorporations of iPSC technology, microphysiological systems, clinical pan-omics, and artificial intelligence to improve success rates and advance cardiovascular healthcare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Effective tissue repair after myocardial infarction entails a vigorous angiogenic response, guided by incompletely defined immune cell-endothelial cell interactions. We identify the monocyte- and macrophage-derived cytokine METRNL (meteorin-like) as a driver of postinfarction angiogenesis and high-affinity ligand for the stem cell factor receptor KIT (KIT receptor tyrosine kinase). METRNL mediated angiogenic effects in cultured human endothelial cells through KIT-dependent signaling pathways. In a mouse model of myocardial infarction, METRNL promoted infarct repair by selectively expanding the KIT-expressing endothelial cell population in the infarct border zone. Metrnl -deficient mice failed to mount this KIT-dependent angiogenic response and developed severe postinfarction heart failure. Our data establish METRNL as a KIT receptor ligand in the context of ischemic tissue repair.

Objectives: To develop a Brief Adolescent Respiratory System Health Assessment Scale-Student Version (BARSHAS-SV) and test the validity and reliability of the scale. Methods: Considering common respiratory system diseases and respiratory system symptoms as a theoretical basis, researchers developed a Brief Adolescent Respiratory System Health Assessment Scale-Student Version-I (BARSHAS-SV-I). After six medical experts reviewed the BARSHAS-SV-I, and six adolescents tested the BARSHAS-SV-I, researchers developed an updated BARSHAS-SV-II. Researchers randomly selected two middle schools in Baoding, China. Thousand twenty nine valid questionnaires were recovered. Researchers evaluated the validity and reliability of the scale and obtained the final version of the scale (BARSHAS-SV). The exploratory factor analysis (EFA) and the confirmatory factor analysis (CFA) were used to evaluate the construct validity of the scale. The content validity index (CVI) was used to evaluate the content validity of the scale. The Cronbach's α coefficient and the mean inter-item correlation coefficient (MIIC) were used to assess the reliability of the scale. Results: BARSHAS-SV Cronbach's α = 0.910, content validity = 0.941, and factor cumulative variance contribution rate = 64.047% conducting EFA. Conducting CFA, Chi square value (χ2) = 233.806, degrees of freedom (df) = 106, Chi square value/degree of freedom (χ2/df) = 2.206, root-mean-square error of approximation (RMSEA) = 0.063, normed fit index (NFI) = 0.922, goodness of fit index (GFI) = 0.917, Tueker-Lewis index (TLI) = 0.942, comparative fit index (CFI) = 0.955, incremental fit index (IFI) = 0.956. BARSHAS-SV consisted of 4 dimensions and 17 items. Four factors were as follows: Factor 1, mild respiratory system diseases (Cronbach's α coefficient = 0.781); Factor 2, severe respiratory system diseases (Cronbach's α coefficient = 0.829); Factor 3, respiratory system symptoms (Cronbach's α coefficient = 0.835); Factor 4, treatment and recovery of respiratory system diseases (Cronbach's α coefficient = 0.845). Conclusions: BARSHAS-SV is a valid and reliable method that can be applied to assess adolescent respiratory system health status. BARSHAS-SV may help teachers and medical staff in schools to quickly and conveniently evaluate the adolescent respiratory system health status and identify respiratory issues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tao, Gao, Dou, Wu, Yan, Liu, Zhao, Zhao, Wang and Zhang.)