Advances in mesenchymal stem cell-derived extracellular vesicles therapy for Sjogren's syndrome-related dry eye disease.

Sjogren's syndrome (SS) is a chronic autoimmune disorder that affects exocrine glands, particularly lacrimal glands, leading to dry eye disease (DED). DED is a common ocular surface disease that affects millions of people worldwide, causing discomfort, visual impairment, and even blindness in severe cases. However, there is no definitive cure for DED, and existing treatments primarily relieve symptoms. Consequently, there is an urgent need for innovative therapeutic strategies based on the pathophysiology of DED. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic tool for various autoimmune disorders, including SS-related DED (SS-DED). A particularly intriguing facet of MSCs is their ability to produce extracellular vesicles (EVs), which contain various bioactive components such as proteins, lipids, and nucleic acids. These molecules play a key role in facilitating communication between cells and modulating a wide range of biological processes. Importantly, MSC-derived EVs (MSC-EVs) have therapeutic properties similar to those of their parent cells, including immunomodulatory, anti-inflammatory, and regenerative properties. In addition, MSC-EVs offer several notable advantages over intact MSCs, including lower immunogenicity, reduced risk of tumorigenicity, and greater convenience in terms of storage and transport. In this review, we elucidate the underlying mechanisms of SS-DED and discuss the relevant mechanisms and targets of MSC-EVs in treating SS-DED. In addition, we comprehensively review the broader landscape of EV application in autoimmune and corneal diseases. This review focuses on the efficacy of MSC-EVs in treating SS-DED, a field of study that holds considerable appeal due to its multifaceted regulation of immune responses and regenerative functions.

Circular RNA POSTN Promotes Myocardial Infarction-Induced Myocardial Injury and Cardiac Remodeling by Regulating miR-96-5p/BNIP3 Axis.

Myocardial infarction (MI) is the most prevalent cardiac disease with high mortality, leading to severe heart injury. Circular RNAs (circRNAs) are a new type of regulatory RNAs and participate in multiple pathological cardiac progressions. However, the role of circRNAs Postn (circPostn) in MI modulation remains unclear. Here, we aimed to explore the effect of circPostn on MI-induced myocardial injury and cardiac remodeling. We identified that the expression of circPostn was elevated in the plasma of MI patients, MI mouse model, and hypoxia and reoxygenation (H/R)-treated human cardiomyocytes. The depletion of circPostn significantly attenuated MI-related myocardium injury and reduced the infarct size in MI mouse model. The circPostn knockdown obviously enhanced left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) and inhibited left ventricular anterior wall thickness at diastole (LVAWd) and left ventricular posterior wall thickness at diastole (LVPWd). The depletion of circPostn was able to decrease MI-induced expression of collagen 1α1 and collagen 3α1 in the ventricular tissues of mice. The protein expression of collagen and α-smooth muscle actin (SMA) was up-regulated in MI mice and was inhibited by circPostn knockdown. Meanwhile, the expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was repressed by circPostn depletion in the ventricular tissues of MI mice. Besides, the circPostn depletion attenuated cardiomyocyte apoptosis in mice. Mechanically, circPostn served as a miR-96-5p sponge and miR-96-5p-targeted BNIP3 in human cardiomyocytes, in which circPostn up-regulated BNIP3 expression by targeting miR-96-5p. circPostn promoted H/R-induced cardiomyocyte injury by modulating miR-96-5p/BNIP3 axis. Thus, we conclude that circPostn contributes to MI-induced myocardial injury and cardiac remodeling by regulating miR-96-5p/BNIP3 axis. Our finding provides new insight into the mechanism by which circPostn regulates MI-related cardiac dysfunction. circPostn, miR-96-5p, and BNIP3 are potential targets for the treatment of MI-caused heart injury.