RESUMO
In recent years, there has been a significant increase in the incidence of metabolic-associated fatty liver disease (MAFLD), which has been attributed to the increasing prevalence of type 2 diabetes mellitus (T2DM) and obesity. MAFLD affects more than one-third of adults worldwide, making it the most prevalent liver disease globally. Moreover, MAFLD is considered a significant risk factor for hepatocellular carcinoma (HCC), with MAFLD-related HCC cases increasing. Approximately 1 in 6 HCC patients are believed to have MAFLD, and nearly 40â¯% of these HCC patients do not progress to cirrhosis, indicating direct transformation from MAFLD to HCC. N6-methyladenosine (m6A) is commonly distributed in eukaryotic mRNA and plays a crucial role in normal development and disease progression, particularly in tumors. Numerous studies have highlighted the close association between abnormal m6A modification and cellular metabolic alterations, underscoring its importance in the onset and progression of MAFLD. However, the specific impact of m6A modification on the progression of MAFLD to HCC remains unclear. Can targeting m6A effectively halt the progression of MAFLD-related HCC? In this review, we investigated the pivotal role of abnormal m6A modification in the transition from MAFLD to HCC, explored the potential of m6A modification as a therapeutic target for MAFLD-related HCC, and proposed possible directions for future investigations.
RESUMO
Currently, the clinical outcomes of peripheral nerve injuries are suboptimal, highlighting the urgent need to understand the mechanisms of nerve injury to enhance treatment strategies. Muscle-derived stem cells (MDSCs) are a diverse group of multipotent cells that hold promise for peripheral nerve regeneration due to their strong antioxidant and regenerative properties. Our research has revealed that severe ferroptosis occurs in the sciatic nerve and ipsilateral dorsal root ganglion following sciatic nerve injury. Interestingly, we have observed that MDSC-derived exosomes effectively suppress cell ferroptosis and enhance cell viability in Schwann cells and dorsal root ganglion cells. Treatment with exosomes led to increased expression of BDNF and P62 in Schwann cells, decreased expression of Keap1, Nrf2, and HO-1 in Schwann cells, and upregulated dorsal root ganglion cells. Rats treated with exosomes exhibited improvements in sciatic nerve function, sensitivity to stimuli, and reduced muscle atrophy, indicating a positive impact on post-injury recovery. In conclusion, our findings demonstrate the occurrence of ferroptosis in the sciatic nerve and dorsal root ganglion post-injury, with MDSC exosomes offering a potential therapeutic strategy by inhibiting ferroptosis, activating the Keap1-Nrf2-HO-1 pathway, and optimizing the post-injury repair environment.
RESUMO
Introduction: This study aimed to investigate the effect of muscle-derived stem cell (MDSC) exosomes with overexpressed miR-214 on the regeneration and repair of rat sciatic nerve after crush injury and its molecular mechanism. Methods: First, primary MDSCs, Schwann cells (SCs) and dorsal root ganglion (DRG) neurons were isolated and cultured, and the characteristics of MDSCs-derived exosomes were identified by molecular biology and immunohistochemistry. NC mimics and miR-214 mimics were transfected to obtain exo-NC and exo-miR-214. An in vitro co-culture system was established to determine the effect of exo-miR-214 on nerve regeneration. The restoration of sciatic nerve function of rats by exo-miR-214 was evaluated by walking track analysis. Immunofluorescence for NF and S100 was used to detect the regeneration of axon and myelin sheath in injured nerve. The Starbase database was used to analyze the downstream target genes of miR-214. QRT-PCR and dual luciferase reporter assays were used to validate the miR-214 and PTEN interaction relationship. And the expression of the JAK2/STAT3 pathway-related proteins in sciatic nerve tissues were detected by western blot. Results: The above experiments showed that MDSCs-derived exosomes with overexpressed miR-214 was found to promote the proliferation and migration of SCs, increase the expression of neurotrophic factors, promote axon extension of DRG neurons and positively affect the recovery of nerve structure and function. In addition, PTEN was a target gene of miR-214. Exo-miR-214 can significantly inhibit the expression level of PTEN, increase the protein expression levels of p-JAK2 and p-STAT3 and the ratio of p-JAK2/JAK2 and p-STAT3/STAT3, also MDSCs-derived exosomes with overexpressed miR-214 can reduce the occurrence of denervated muscle atrophy. Conclusion: In summary, the MDSCs-derived exosomes with overexpressed miR-214 is involved in peripheral nerve regeneration and repair in rats after sciatic nerve crush injury to activate the JAK2/ STAT3 pathway by targeting PTEN.
RESUMO
Long noncoding RNAs (lncRNAs) have been shown to play key roles in various human tumors. Ectopic expression of the lncRNA FEZ finger zinc 1 antisense 1 (FEZF1-AS1) have been reported in different cancers, including colorectal cancer, gastric neoplasia, hepatocellular carcinoma and so on. Summarizing all literature correlated with FEZF1-AS1, it is obvious that FEZF1-AS1 is mainly involved in tumorigenesis and progression through competing endogenous RNA (ceRNA) which sponges tumor-suppressive microRNA (miRNA) and recruiting mechanism. Moreover, the aberrant expression of FEZF1-AS1 is related to clinical features of patients with cancers, and regulates cellular proliferation, anti-apoptosis, invasion and metastasis through diverse underlying mechanisms. The role of FEZF1-AS1 in carcinogenesis and progression suggests that it may be a potential diagnostic biomarker or a novel therapeutic target for cancers.
