We have collected the most exciting new researches in the field of genetics and cellular research in the past week.
Exosomes regulate SIRT3-related autophagy by delivering miR-421 to regulate macrophage polarization and participate in OSA-related NAFLD
Purpose
To analyze the role of and mechanism underlying obstructive sleep apnea (OSA)-derived exosomes in inducing non-alcoholic fatty liver (NAFLD).
Methods
The role of OSA-derived exosomes was analyzed in inducing hepatocyte fat accumulation in mice models both in vivo and in vitro.
Results
OSA-derived exosomes caused fat accumulation and macrophage activation in the liver tissue. These exosomes promoted fat accumulation; steatosis was more noticeable in the presence of macrophages. Macrophages could internalize OSA-derived exosomes, which promoted macrophage polarization to the M1 type. Moreover, it inhibited sirtuin-3 (SIRT3)/AMP-activated protein kinase (AMPK) and autophagy and promoted the activation of nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3) inflammasomes. The use of 3-methyladenine (3-MA) to inhibit autophagy blocked NLRP3 inflammasome activation and inhibited the M1 polarization of macrophages. miR-421 targeting inhibited SIRT3 protein expression in the macrophages. miR-421 was significantly increased in OSA-derived exosomes. Additionally, miR-421 levels were increased in OSA + NAFLD mice- and patient-derived exosomes. In the liver tissues of OSA and OSA + NAFLD mice, miR-421 displayed similar co-localization with the macrophages. Intermittent hypoxia-induced hepatocytes deliver miR-421 to the macrophages via exosomes to inhibit SIRT3, thereby participating in macrophage M1 polarization. After OSA and NAFLD modeling in miR-421−/− mice, liver steatosis and M1 polarization were significantly reduced. Additionally, in the case of miR-421 knockout, the inhibitory effects of OSA-derived exosomes on SIRT3 and autophagy were significantly alleviated. Furthermore, their effects on liver steatosis and macrophage M1 polarization were significantly reduced.
Conclusions
OSA promotes the delivery of miR-421 from the hepatocytes to macrophages. Additionally, it promotes M1 polarization by regulating the SIRT3/AMPK-autophagy pathway, thereby causing NAFLD.
Exosomes: How tumors escape the immune system
Mutations in the gene for β-catenin cause liver cancer cells to release fewer exosomes, which reduces the number of immune cells infiltrating the tumor.
Combined exosome of adipose-derived mesenchymal stem cell and hyaluronic acid delays early osteoarthritis progression of ovine sheep model: Clinical, radiographic and macroscopic evaluation
Background
Current treatment of osteoarthritis (OA) mainly focused on treating symptoms. Exosome from Adipose-derived Mesenchymal Stem Cell (Ad-MSC) have been shown to delay degenerative process. This study aimed to investigate the clinical, radiological and histological impact of combined intra-articular (IA) hyaluronic acid (HA) and exosome Ad-MSCs in-vivo using a larger animal model with low-grade OA.
Methods
Eighteen male Ovies aries sheep underwent total lateral meniscectomy and conventional radiography was performed to confirm low-grade OA after 6 weeks. The sheep were divided into three groups, Group 1 (G1; n=6) received thrice exosome injections, G2 (n=6) received twice HA injection, and G3 (n=6) received both treatments with a 1-week interval after 10 days of meniscectomy. Clinical evaluations were conducted using the Clinical Lameness Score (CLS), radiographic with X-ray using OA score by Innes et al, while macroscopic evaluation by Osteoarthritis Research Society International (OARSI) scores.
Results
Lameness parameter scored lowest in G3 significantly (2.0±0.0 VS 2.7±0.52 VS 2.7±0.52; p=0.024) at the second month although the overall CLS score did not significantly differ at the 3rd month. The best improvement of conventional total OA radiographic score at the 3rd month compared to all groups (5.2±1.17 vs 6.3±0.82 vs 6.7±1.03; p=0.053). Macroscopic OARSI evaluation showed no difference (p=0.711).
Conclusions
Combined repeated exosome Ad-MSC and HA IA injection proven to delay OA progression, however longer duration of follow up is required to evaluate its long-term effect.
Methods of Exosome Isolation
As major biomarkers in the early diagnosis of cancer, as well as inflammatory, cardiovascular, and neurodegenerative diseases, exosomes are a prominent area of disease research. But in order for this research to occur, an efficient and reliable method of exosome isolation is required. However, despite this critical need, the heterogeneity of exosomes, the complexity of biological fluids, and the presence of nanoscale contaminants mean that exosome separation is no mean feat. Nevertheless, various methods of exosome isolation exist, and the methods are continually improving. The key is choosing the method that best suits your needs.
Stem cells derived exosomes as biological nano carriers for VCR sulfate for treating breast cancer stem cell
Exosomes are tiny, naturally occurring vesicles secreted by cells that play a key role in cell-to-cell communication. These vesicles can carry proteins, RNA, and other molecules to specific cells and tissues, making them ideal candidates for targeted drug delivery. In this study, researchers at MSA University used exosomes derived from mesenchymal stem cells (MSCs) to deliver VCR sulfate directly to cancer cells.