Search

Methamphetamine (Meth) is a highly addictive substance and the largest drug threat across the globe. There is evidence to indicate that Meth use has serious damage on central nervous system (CNS) and heart in several animal and human studies. However, the connection in the process of Meth addiction between these two systems has not been determined. Emerging data suggest that extracellular vesicles (EVs) carrying behavior-altering microRNA (miRNAs) play a crucial role in cell communication between CNS and peripheral system. Rhynchophylline (Rhy), an antiaddictive alkaloid, was used to protect the brain and heart from Meth-induced damage, which has caught our attention. Here, we used Meth-dependent conditioned place preference (CPP) animal model and cell model to verify the protective effect of Rhy-treated EVs. Further, small RNA sequencing analysis, qPCR, dual-luciferase reporter assay, and transfection test were used to identify the key EVs-encapsulated miRNAs, isolated from cultured H9c2 cells with different treatments, involved in the therapeutic effect and the underlying mechanisms of Rhy. The results demonstrate that Rhy-treated EVs exert protective effects against Meth dependence through the pathway of miR-183-5p-neuregulin-1 (NRG1). Our collective findings provide novel insights into the roles of EVs miRNAs in Meth addiction and support their potential application in the development of novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

The pathogenesis of osteoporosis is considered extremely intricate. Osteoblast differentiation and angiogenesis can greatly affect bone development and formation, given their coupling role in these processes. Exosome-mediated miRNA regulates cellular senescence, proliferation, and differentiation. However, whether senescent osteoblasts can regulate the senescence of vascular endothelial cell by miRNA through exosomal pathway remains unclear. In this study, senescent osteoblasts could regulate endothelial cell function, promote cell senescence and apoptosis, and decrease cell proliferation via exosomal pathway. miR-139-5p showed high expression in senescent osteoblasts and their exosomes. After senescent osteoblast-derived exosome treatment, miR-139-5p was also upregulated in endothelial cells. Furthermore, transfection of miR-139-5p mimic promoted the senescence and apoptosis of vascular endothelial cells and inhibited their proliferation and migration, whereas transfection of miR-139-5p inhibitor rescued the effect of D-galactose. Using double luciferase assay, TBX1 was confirmed to be a direct target gene of miR-139-5p. In conclusion, senescent osteoblast-derived exosome-mediated miR-139-5p regulated endothelial cell function via exosomal pathway. Our study revealed the role of osteoblast-derived exosomes in the bone environment during aging, providing a clue for inventing a new target therapy. [ABSTRACT FROM AUTHOR]

To observe the expression of MMP-2 and MMP-9 and of the FAK/PI3K/Akt signaling pathway in HSK. Fifty BALB/c mice were infected to establish the model and killed on days 0, 2, 7, 14, and 28. The cornea samples were prepared, respectively. Slit lamp examination, immunofluorescence staining, reverse transcription PCR, and Western blot were used to detect the index. After HSV-1 infection, different degrees of epithelial or stromal damage and corneal opacity were observed. Immunofluorescence staining showed that the expressions of MMP-2 and MMP-9 at different levels of corneal tissue were observed on the 0d, 2d, 7d, 14d, and 28d. Compared with 0d, the relative expression levels of MMP-2 and MMP-9 mRNA at 2d, 7d, 14d, and 28d were significantly increased (all P< 0.05). Compared with 14d, the relative expression of MMP-2 and MMP-9 mRNA decreased on the 2d, 7d, and 28d (all P< 0.05). Western blot showed that the protein expressions of p-FAK, p-PI3K, p-Akt, MMP-2, and MMP-9 at 2d, 14d, and 28d were all significantly higher than 0d (all P< 0.05). At 14 d, the expressions of p-FAK, p-PI3K, p-Akt, and MMP-2 were significantly higher than those at 2d, 7d, and 28d (all P< 0.05). The protein expression of FAK, PI3K, and Akt in corneal of mice in each time period had no significant (all P> 0.05). These data suggest that FAK/PI3K/Akt signaling pathway and MMP-2 and MMP-9 may be involved in the development of HSK. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are deregulated in various vascular ailments including abdominal aortic aneurysm (AAA). MiR-103 is involved in vascular, metabolic, and malignant diseases, but whether it participates in the pathogenesis of AAA remains elusive. ADAM10 plays a vital role in the formation of aneurysm, but whether miRs modulate its activity during AAA formation is totally unknown. In this study, we detected the significantly increased protein expression of ADAM10 in angiotensin II induced murine AAA specimens, while the mRNA expression of ADAM10 was similar between AAA and control, suggesting the posttranscriptional regulation. The ADAM10 specific inhibitor GI254023X dramatically reduced the macrophage infiltration of murine abdominal aorta. Bioinformatic predictions suggest that ADAM10 is the target of miR-103a/107 but the binding site is exclusive. At the cellular level, miR-103a-1 suppressed the protein expression of ADAM10, while antisense miR-103a-1 increased its expression. Particularly, with the progression of murine AAA, the mRNA expression of miR-103a/107 substantially decreased and the protein expression of ADAM10 greatly increased. Together, our data afford the new insight that miR-103a inhibited AAA growth via targeting ADAM10, which might be a promising therapeutic strategy to alleviate AAA. [ABSTRACT FROM AUTHOR]