Microglia, characterized by responding to damage, regulating the secretion of soluble inflammatory mediators, and engulfing specific segments in the central nervous system (CNS), function as key immune cells in the CNS. Emerging evidence suggests that microglia coordinate the inflammatory responses in CNS system and play a pivotal role in the pathogenesis of age-related neurodegenerative diseases (NDDs). Remarkably, microglia autophagy participates in the regulation of subcellular substances, which includes the degradation of misfolded proteins and other harmful constituents produced by neurons. Therefore, microglia autophagy regulates neuronal homeostasis maintenance and process of neuroinflammation. In this review, we aimed at highlighting the pivotal role of microglia autophagy in the pathogenesis of age-related NDDs. Besides the mechanistic process and the co-interaction between microglia autophagy and different kinds of NDDs, we also emphasized potential therapeutic agents and approaches that could be utilized at the onset and progression of these diseases through modulating microglia autophagy, including promising nanomedicines. Our review provides a valuable reference for subsequent studies focusing on treatments of neurodegenerative disorders. The exploration of microglia autophagy and the development of nanomedicines greatly enhances current understanding of NDDs.
BackgroundAdiponectin (APN) is an endogenous adipokine secreted from adipocytes that exerts anti-inflammatory properties. AdipoAI is an orally active adiponectin receptor agonist identified by our group that can emulate APN's anti-inflammatory properties through mechanisms that are not fully understood. LncRNAs, a type of noncoding RNA more than 200 bp in length, have been demonstrated to have abundant biological functions, including in anti-inflammatory responses.Materials and ResultIn the current study, we performed a lncRNA microarray in LPS-induced Raw264.7 cells that were prestimulated with AdipoAI and screened 110 DElncRNAs and 190 DEmRNAs. Enrichment analyses were conducted on total mRNAs and DEmRNAs, including GSVA, ssGSEA, GO/KEGG, GSEA, and PPI analysis. Among all these processes, endocytosis was significantly enriched. A coexpression analysis was built based on DElncRNAs and DEmRNAs. Then, using TargetScan and miRwalk to predict related microRNAs of DElncRNAs and DEmRNAs, respectively, we established competing endogenous RNA (ceRNA) networks including 54 mRNAs from 8 GO items. Furthermore, 33 m6A methylation-related marker genes were obtained from a previous study and used for the construction of an m6A-related lncRNA network by coexpression analysis. We identified FTO as the hub gene of the network and 14 lncRNAs that interacted with it. The expression levels of 10 lncRNAs selected from ceRNA and FTO-related lncRNA networks were validated with qRT‒PCR. Finally, macrophage phenotype scores showed that AdipoAI could attenuate the M2b and M2c polarization of macrophages and correlate with the above lncRNAs.ConclusionOur work reveals that lncRNAs might be involved in the anti-inflammation process of AdipoAI in LPS-induced macrophages through the ceRNA network and the epigenetic regulation of m6A. Mechanistically, these lncRNAs associated with AdipoAI might be related to endocytosis and polarization in macrophages and provide new candidates for the anti-inflammatory application of APN and its receptor agonist.
The green transformation of agricultural production is one of the important measures to promote the high-quality development of agriculture and realize rural revitalization. As a big agricultural country, although China has made great achievements in the process of agricultural development, the problem of resources and environment cannot be ignored. In the process of implementing the rural revitalization strategy, it is necessary to strengthen compliance with the principles of green development, practice the concept of green production, and create a green rural industrial environment. Through a comprehensive analysis of rural revitalization strategies, the problems faced in the process of rural green development are pointed out, and their improvement strategies are proposed.
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