Targeting NPM1 Epigenetically Promotes Postinfarction Cardiac Repair by Reprogramming Reparative Macrophage Metabolism.

Background: Reparative macrophages play a crucial role in limiting excessive fibrosis and promoting cardiac repair after myocardial infarction (MI), highlighting the significance of enhancing their reparative phenotype for wound healing. Metabolic adaptation orchestrates the phenotypic transition of macrophages; however, the precise mechanisms governing metabolic reprogramming of cardiac reparative macrophages remain poorly understood. In this study, we investigated the role of NPM1 (nucleophosmin 1) in the metabolic and phenotypic shift of cardiac macrophages in the context of MI and explored the therapeutic effect of targeting NPM1 for ischemic tissue repair.

IRG1 prevents excessive inflammatory responses and cardiac dysfunction after myocardial injury.

Acute myocardial infarction (MI) and chemotherapeutic drug administration can induce myocardial damage and cardiomyocyte cell death, and trigger the release of damage-associated molecular patterns (DAMPs) that initiate the aseptic inflammatory response. The moderate inflammatory response is beneficial for repairing damaged myocardium, while an excessive inflammatory response exacerbates myocardial injury, promotes scar formation, and results in a poor prognosis of cardiac diseases. Immune responsive gene 1 (IRG1) is specifically highly expressed in activated macrophages and mediates the production of tricarboxylic acid (TCA) cycle metabolite itaconate.

Murine neonatal cardiac B cells promote cardiomyocyte proliferation and heart regeneration.

The irreversible loss of cardiomyocytes in the adult heart following cardiac injury leads to adverse cardiac remodeling and ventricular dysfunction. However, the role of B cells in cardiomyocyte proliferation and heart regeneration has not been clarified. Here, we found that the neonatal mice with B cell depletion showed markedly reduced cardiomyocyte proliferation, leading to cardiac dysfunction, fibrosis scar formation, and the complete failure of heart regeneration after apical resection.

Loss of KDM5B ameliorates pathological cardiac fibrosis and dysfunction by epigenetically enhancing ATF3 expression.

Excessive cardiac fibrosis is central to adverse cardiac remodeling and dysfunction leading to heart failure in many cardiac diseases. Histone methylation plays a crucial role in various pathophysiological events. However, the role of histone methylation modification enzymes in pathological cardiac fibrosis needs to be fully elucidated.

Single-cell transcriptome atlas reveals protective characteristics of COVID-19 mRNA vaccine.

Messenger RNA (mRNA) vaccines are promising alternatives to conventional vaccines in many aspects. We previously developed a lipopolyplex (LPP)-based mRNA vaccine (SW0123) that demonstrated robust immunogenicity and strong protective capacity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in mice and rhesus macaques. However, the immune profiles and mechanisms of pulmonary protection induced by SW0123 remain unclear.

Metabolic Regulation of Cardiac Regeneration.

The mortality due to heart diseases remains highest in the world every year, with ischemic cardiomyopathy being the prime cause. The irreversible loss of cardiomyocytes following myocardial injury leads to compromised contractility of the remaining myocardium, adverse cardiac remodeling, and ultimately heart failure. The hearts of adult mammals can hardly regenerate after cardiac injury since adult cardiomyocytes exit the cell cycle.

PHLPP1 deficiency ameliorates cardiomyocyte death and cardiac dysfunction through inhibiting Mcl-1 degradation.

Myocardial infarction (MI), ischemia-reperfusion injury or chemotherapy can trigger excessive loss of terminally differentiated cardiomyocytes, leading to the development of heart failure. Whereas apoptosis has been considered to be the major form of cell death in various myocardial damage, the means by which to reduce cardiomyocyte loss are limited, and the mechanism that underlies cardiomyocyte apoptosis need to be further investigated. PH domain leucine-rich repeat protein phosphatase1 (PHLPP1) belongs to a novel family of Ser/Thr protein phosphatases that functions as a tumor suppressor.