Spatiotemporal control of neutrophil fate to tune inflammation and repair for myocardial infarction therapy.

Neutrophils are critical mediators of both the initiation and resolution of inflammation after myocardial infarction (MI). Overexuberant neutrophil signaling after MI exacerbates cardiomyocyte apoptosis and cardiac remodeling while neutrophil apoptosis at the injury site promotes macrophage polarization toward a pro-resolving phenotype. Here, we describe a nanoparticle that provides spatiotemporal control over neutrophil fate to both stymie MI pathogenesis and promote healing.

Daily oral administration of probiotics engineered to constantly secrete short-chain fatty acids effectively prevents myocardial injury from subsequent ischaemic heart disease.

Aims: Given the extremely limited regeneration potential of the heart, one of the most effective strategies to reduce the prevalence and mortality of coronary artery disease is prevention. Short-chain fatty acids (SCFAs), which are by-products of beneficial probiotics, have been reported to possess cardioprotective effects. Despite their beneficial roles, delivering SCFAs and maintaining their effective concentration in plasma present major challenges.

Hyaluronic acid stimulation of stem cells for cardiac repair: a cell-free strategy for myocardial infarct.

Background: Myocardial infarction (MI), a representative form of ischemic heart disease, remains a huge burden worldwide. This study aimed to explore whether extracellular vesicles (EVs) secreted from hyaluronic acid (HA)-primed induced mesenchymal stem cells (HA-iMSC-EVs) could enhance the cardiac repair after MI.

Results: HA-iMSC-EVs showed typical characteristics for EVs such as morphology, size, and marker proteins expression.

On-chip droplet analysis and cell spheroid screening by capillary wrapping enabled shape-adaptive ferrofluid transporters.

Non-invasive droplet manipulation with no physical damage to the sample is important for the practical value of manipulation tools in multidisciplinary applications from biochemical analysis and diagnostics to cell engineering. It is a challenge to achieve this for most existing photothermal, electric stimuli, and magnetic field-based technologies. Herein, we present a droplet handling toolbox, the ferrofluid transporter, for non-invasive droplet manipulation in an oil environment.

Core-Shell Droplet-Based Angiogenic Patches for the Treatment of Ischemic Diseases: Ultrafast Processability, Physical Tunability, and Controlled Delivery of an Angiogenic Cocktail.

The patch-based delivery system has been a promising therapeutic approach for treating various vascular diseases. However, conventional methods face several challenges, including labor-intensive and time-consuming processes associated with patch fabrication or factor incorporation, inadequate physical properties, and uncontrolled release of factors. These limitations restrict the potential applications in clinical settings.

The Gut-Heart Axis: Updated Review for The Roles of Microbiome in Cardiovascular Health.

Cardiovascular diseases (CVDs), including coronary artery disease, stroke, heart failure, and hypertension, are the global leading causes of death, accounting for more than 30% of deaths worldwide. Although the risk factors of CVDs have been well understood and various treatment and preventive measures have been established, the mortality rate and the financial burden of CVDs are expected to grow exponentially over time due to the changes in lifestyles and increasing life expectancies of the present generation. Recent advancements in metagenomics and metabolomics analysis have identified gut microbiome and its associated metabolites as potential risk factors for CVDs, suggesting the possibility of developing more effective novel therapeutic strategies against CVD.

Are There Hopeful Therapeutic Strategies to Regenerate the Infarcted Hearts?

Ischemic heart disease remains the primary cause of morbidity and mortality worldwide. Despite significant advancements in pharmacological and revascularization techniques in the late 20th century, heart failure prevalence after myocardial infarction has gradually increased over the last 2 decades. After ischemic injury, pathological remodeling results in cardiomyocytes (CMs) loss and fibrosis, which leads to impaired heart function.

Hybrid assembly of polymeric nanofiber network for robust and electronically conductive hydrogels.

Electroconductive hydrogels have been applied in implantable bioelectronics, tissue engineering platforms, soft actuators, and other emerging technologies. However, achieving high conductivity and mechanical robustness remains challenging. Here we report an approach to fabricating electroconductive hydrogels based on the hybrid assembly of polymeric nanofiber networks.

Three-dimensional heart extracellular matrix enhances chemically induced direct cardiac reprogramming.

Direct cardiac reprogramming has emerged as a promising therapeutic approach for cardiac regeneration. Full chemical reprogramming with small molecules to generate cardiomyocytes may be more amenable than genetic reprogramming for clinical applications as it avoids safety concerns associated with genetic manipulations. However, challenges remain regarding low conversion efficiency and incomplete cardiomyocyte maturation.

Sutureless transplantation ofpriming human mesenchymal stem cell sheet promotes the therapeutic potential for cardiac repair.

The heart, contrary to its small size, vigorously pumps oxygen and nutrients to our entire body indeterminably; and thus, its dysfunction could be devastating. Until now, there ave been several major obstacles to applying a cardiac patch for the treatment for myocardial infarction, including poor integration and low engraftment rates, due to the highly-curved surface of the heart and its dynamic nature. Here, we demonstrate a novel way for a comprehensive cardiac repair achieved by the sutureless transplantation of a highly integrablepriming bone marrow mesenchymal stem cell (BMSC) sheet based on the utilization of a highly aligned thermoresponsive nanofiber membrane.

Enhancement strategy for effective vascular regeneration following myocardial infarction through a dual stem cell approach.

Since an impaired coronary blood supply following myocardial infarction (MI) negatively affects heart function, therapeutic neovascularization is considered one of the major therapeutic strategies for cell-based cardiac repair. Here, to more effectively achieve therapeutic neovascularization in ischemic hearts, we developed a dual stem cell approach for effective vascular regeneration by utilizing two distinct types of stem cells, CD31-endothelial cells derived from human induced pluripotent stem cells (hiPSC-ECs) and engineered human mesenchymal stem cells that continuously secrete stromal derived factor-1α (SDF-eMSCs), to simultaneously promote natal vasculogenesis and angiogenesis, two core mechanisms of neovascularization. To induce more comprehensive vascular regeneration, we intramyocardially injected hiPSC-ECs to produce de novo vessels, possibly via vasculogenesis, and a 3D cardiac patch encapsulating SDF-eMSCs (SDF-eMSC-PA) to enhance angiogenesis through prolonged secretion of paracrine factors, including SDF-1α, was implanted into the epicardium of ischemic hearts.

Irx5 and transient outward K currents contribute to transmural contractile heterogeneities in the mouse ventricle.

Previous studies have established that transmural gradients of the fast transient outward K current () correlate with regional differences in action potential (AP) profile and excitation-contraction coupling (ECC) with high expression in the epimyocardium (EPI) being associated with short APs and low contractility and vice versa. Herein, we investigated the effects of altering the gradients on transmural contractile properties using mice lacking (Irx5-KO) or lacking (K4.2-KO) or both.

PROX1, a Key Mediator of the Anti-Proliferative Effect of Rapamycin on Hepatocellular Carcinoma Cells.

The MTOR signal is known to be activated in various cancer cells including hepatocellular carcinoma (HCC) cells. Rapamycin, a specific inhibitor of MTOR, has been widely used as an immunosuppressant in organ transplant patients, and its clinical application has been recently expanded to cancer therapy. In this study, the anti-proliferative effect of rapamycin was investigated in four different HCC cell lines.

CU06-1004 enhances vascular integrity and improves cardiac remodeling by suppressing edema and inflammation in myocardial ischemia-reperfusion injury.

Ischemia-reperfusion (I/R) injury accelerates the cardiomyocytes (CMs) death by oxidative stress, and thereby deteriorates cardiac function. There has been a paradigm shift in the therapeutic perspective more towards the prevention or amelioration of damage caused by reperfusion. Cardiac microvascular endothelial cells (CMECs) are more vulnerable to reperfusion injury and play the crucial roles more than CMs in the pathological process of early I/R injury.

Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database.

On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID-19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO).

Histochrome Attenuates Myocardial Ischemia-Reperfusion Injury by Inhibiting Ferroptosis-Induced Cardiomyocyte Death.

Reactive oxygen species (ROS) and intracellular iron levels are critical modulators of lipid peroxidation that trigger iron-dependent non-apoptotic ferroptosis in myocardial ischemia-reperfusion (I/R) injury. Histochrome (HC), with a potent antioxidant moiety and iron-chelating capacity, is now available in clinical practice. However, limited data are available about the protective effects of HC on ferroptotic cell death in myocardial I/R injury.

Human cardiac stem cells rejuvenated by modulating autophagy with MHY-1685 enhance the therapeutic potential for cardiac repair.

Stem cell-based therapies with clinical applications require millions of cells. Therefore, repeated subculture is essential for cellular expansion, which is often complicated by replicative senescence. Cellular senescence contributes to reduced stem cell regenerative potential as it inhibits stem cell proliferation and differentiation as well as the activation of the senescence-associated secretory phenotype (SASP).

Blue laser-induced selective vasorelaxation by the activation of NOSs.

Phototherapy has been tried for treating cardiovascular diseases. In particular, ultraviolet and blue visible lights were suggested to be useful due to their nitric oxide (NO)-production ability in the skin. However, the effects of blue light on the arterial contractility are controversial.

In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial Infarction.

Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and poor retention following administration into failing hearts. Here, to improve the therapeutic effectiveness of BM-MSCs, we examined a novel therapeutic platform named in situ preconditioning in a rat myocardial infarction (MI) model.

Challenges and Limitations of Strategies to Promote Therapeutic Potential of Human Mesenchymal Stem Cells for Cell-Based Cardiac Repair.

Mesenchymal stem cells (MSCs) represent a population of adult stem cells residing in many tissues, mainly bone marrow, adipose tissue, and umbilical cord. Due to the safety and availability of standard procedures and protocols for isolation, culturing, and characterization of these cells, MSCs have emerged as one of the most promising sources for cell-based cardiac regenerative therapy. Once transplanted into a damaged heart, MSCs release paracrine factors that nurture the injured area, prevent further adverse cardiac remodeling, and mediate tissue repair along with vasculature.