Multiscale drug screening for cardiac fibrosis identifies MD2 as a therapeutic target.

Cardiac fibrosis impairs cardiac function, but no effective clinical therapies exist. To address this unmet need, we employed a high-throughput screening for antifibrotic compounds using human induced pluripotent stem cell (iPSC)-derived cardiac fibroblasts (CFs). Counter-screening of the initial candidates using iPSC-derived cardiomyocytes and iPSC-derived endothelial cells excluded hits with cardiotoxicity.

Next-Gen Therapeutics: Pioneering Drug Discovery with iPSCs, Genomics, AI, and Clinical Trials in a Dish.

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.

Clinical trials in-a-dish for cardiovascular medicine.

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.

Cysteine-rich with EGF-like domains 2 (CRELD2) is an endoplasmic reticulum stress-inducible angiogenic growth factor promoting ischemic heart repair.

Tissue repair after myocardial infarction (MI) is guided by autocrine and paracrine-acting proteins. Deciphering these signals and their upstream triggers is essential when considering infarct healing as a therapeutic target. Here we perform a bioinformatic secretome analysis in mouse cardiac endothelial cells and identify cysteine-rich with EGF-like domains 2 (CRELD2), an endoplasmic reticulum stress-inducible protein with poorly characterized function.

Visible-Light-Induced Oxyalkylation of 1,2,4-Triazine-3,5(2, 4)-diones with Ethers Oxidative Cross-Dehydrogenative Coupling.

An efficient and convenient method to synthesize 6-oxyalkylated 1,2,4-triazine-3,5(2, 4)-diones has been developed visible-light-induced cross-dehydrogenative coupling reaction between 1,2,4-triazine-3,5(2, 4)-diones and ethers with a wide range of functional group tolerance. The present transformation employs the cheap and low-toxic 2--butylanthraquinone as a metal-free photocatalyst and air as a green oxidant at room temperature. Moreover, this reaction can also be driven by sunlight as a clean energy resource.

Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase.

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.

Developing and Testing the Validity and Reliability of the Brief Adolescent Respiratory System Health Assessment Scale-Student Version in a Chinese Sample.

To develop a Brief Adolescent Respiratory System Health Assessment Scale-Student Version (BARSHAS-SV) and test the validity and reliability of the scale. 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.

Myeloid-Derived Growth Factor Protects Against Pressure Overload-Induced Heart Failure by Preserving Sarco/Endoplasmic Reticulum Ca-ATPase Expression in Cardiomyocytes.

Background: Inflammation contributes to the pathogenesis of heart failure, but there is limited understanding of inflammation's potential benefits. Inflammatory cells secrete MYDGF (myeloid-derived growth factor) to promote tissue repair after acute myocardial infarction. We hypothesized that MYDGF has a role in cardiac adaptation to persistent pressure overload.

Angiogenesis after acute myocardial infarction.

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.

Effects of Mobile Text Messaging on Glycemic Control in Patients With Coronary Heart Disease and Diabetes Mellitus: A Randomized Clinical Trial.

Background: Mobile health interventions may support risk factor management and are readily scalable in healthcare systems. We aim to evaluate the efficacy of a text messaging-based intervention to improve glycemic control in patients with coronary heart disease and diabetes mellitus in China.

Methods And Results: The CHAT-DM study (Cardiovascular Health and Texting-Diabetes Mellitus) was a parallel-group, single-blind, randomized clinical trial that included 502 patients with both coronary heart disease and diabetes mellitus from 34 hospitals in China.

Heparan Sulfate-Editing Extracellular Sulfatases Enhance VEGF Bioavailability for Ischemic Heart Repair.

Rationale: Mechanistic insight into the inflammatory response after acute myocardial infarction may inform new molecularly targeted treatment strategies to prevent chronic heart failure.

Objective: We identified the sulfatase SULF2 in an in silico secretome analysis in bone marrow cells from patients with acute myocardial infarction and detected increased sulfatase activity in myocardial autopsy samples. SULF2 (Sulf2 in mice) and its isoform SULF1 (Sulf1) act as endosulfatases removing 6--sulfate groups from heparan sulfate (HS) in the extracellular space, thus eliminating docking sites for HS-binding proteins.

Effect of Text Messaging on Risk Factor Management in Patients With Coronary Heart Disease: The CHAT Randomized Clinical Trial.

Background: Mobile health technologies are low cost, scalable interventions with the potential to promote patient engagement and behavior change. We aimed to test whether a culturally sensitive text messaging intervention supporting secondary prevention improves the control of risk factors in patients with coronary heart disease in China.

Methods And Results: In this multicenter, single-blinded randomized controlled trial, 822 patients (mean age, 56.

Traditional Chinese Medicine for Acute Myocardial Infarction in Western Medicine Hospitals in China.

Background: Amid national efforts to improve the quality of care for people with cardiovascular disease in China, the use of traditional Chinese medicine (TCM) is increasing, yet little is known about its use in the early management of acute myocardial infarction (AMI).

Methods And Results: We aimed to examine intravenous use of TCM within the first 24 hours of hospitalization (early IV TCM) for AMI. Data come from the China Patient-centered Evaluative Assessment of Cardiac Events Retrospective Study of Acute Myocardial Infarction, restricted to a large, representative sample of Western medicine hospitals throughout China (n=162).