Nuclear paraspeckle assembly transcript 1 (Neat1) located at chromosome 11 is a long non-coding RNA that is widely expressed in mammalian cell types, and which is overexpressed in several inflammation-related disorders. Inflammation implies a plethora of mutual interactions between both soluble factors and cells due to various stimuli including tissue injury. Although there is no doubt that inflammation is critically involved in multiple biological and pathological processes alike, the precise mechanisms being involved are still open for debate. In this context, the role of Neat1 as a regulator of inflammation, microglial activation, and lipid accumulation under various inflammatory conditions remains elusive. Herein, we review the regulation of Neat1 and how it modulates the expression of its target genes. Thereafter, we will review the impact of Neat1 on inflammation by activating or inhibiting various signaling pathways, such as microRNAs, AKT, TLR4, TRAF6, and NF-κB.

Hypoxia triggers reactive microglial inflammation and lipid droplet (LD) accumulation under stroke conditions, although the mutual interactions between these two processes are insufficiently understood. Hence, the involvement of transforming growth factor (TGF)-β1 in inflammation and LD accumulation in cultured microglia exposed to hypoxia were analyzed herein. Primary microglia were exposed to oxygen-glucose deprivation (OGD) injury and lipopolysaccharide (LPS) stimulation. For analyzing the role of TGF-β1 patterns under such conditions, a TGF-β1 siRNA and an exogenous recombinant TGF-β1 protein were employed. Further studies applied Triacsin C, an inhibitor of LD formation, in order to directly assess the impact of LD formation on the modulation of inflammation. To assess mutual microglia-to-neuron interactions, a co-culture model of these cells was established. Upon OGD exposure, microglial TGF-β1 levels were significantly increased, whereas LPS stimulation yielded decreased levels. Elevating TGF-β1 expression proved highly effective in suppressing inflammation and reducing LD accumulation in microglia exposed to LPS. Conversely, inhibition of TGF-β1 led to the promotion of microglial cell inflammation and an increase in LD accumulation in microglia exposed to OGD. Employing the LD formation inhibitor Triacsin C, in turn, polarized microglia towards an anti-inflammatory phenotype. Such modulation of both microglial TGF-β1 and LD levels significantly affected the resistance of co-cultured neurons. This study provides novel insights by demonstrating that TGF-β1 plays a protective role against microglia-mediated neuroinflammation through the suppression of LD accumulation. These findings offer a fresh perspective on stroke treatment, suggesting the potential of targeting this pathway for therapeutic interventions.

Pulmonary fibrosis is a type of chronic, progressive, fibrotic lung disease of unclear cause with few treatment options. Cell therapy is emerging as a promising novel modality for facilitating lung repair. Mesenchymal stem cell (MSC)-based and macrophage-based cell therapies are regarded as promising strategies to promote lung repair, due to incredible regenerative potential and typical immunomodulatory function, respectively. Extracellular vesicles (EVs), including exosomes and microvesicles, are cell-derived lipid-bilayer membrane vesicles that are secreted from virtually every cell and are involved in intercellular communication by delivering expansive biological cargos to recipients. This review provides a deep insight into the recent research progress concerning the effects of MSC and macrophage-associated EVs on the pathogenesis of pulmonary fibrosis. In addition to discussing their respective vital roles, we summarize the importance of cross-talk, as macrophages are vital for MSCs to exert their protective effects through two major patterns, including attenuating macrophage activation and M1 phenotype macrophage polarization. Moreover, miRNAs are selectively enriched into EVs as essential components, and consideration is given to the particular effects of EV-associated miRNAs.

Eukaryotic cells release different types of extracellular vesicles (EVs), including exosomes, apoptotic bodies and microvesicles. EVs carry proteins, lipids and nucleic acids specific to cells and cell states. Autophagy is an intracellular degradation process, which, along with EVs, can significantly affect the development and progression of neurological diseases and, therefore, has been the hotspot. Generally, EVs and autophagy are closely associated. EVs and autophagy can interact with each other. On the one hand, the level of autophagy in target cells is closely related to the secretion and transport of EVs. In another, the application of EVs provides a great opportunity for adjuvant treatment of neurological disorders, for which autophagy is an excellent target. EVs can release their cargos into target cells, which, in turn, regulate the autophagic level of target cells through autophagy-related proteins directly and the non-coding RNA, signal transducer and activator of transcription 3 (STAT3), phosphodiesterase enzyme (PDE) 1-B, etc. signaling pathways indirectly, thus regulating the development of related neurological disorders.