B cell activation factor of the TNF family (BAFF/BLyS), an essential B cell survival factor of which circulating levels are elevated in several autoimmune disorders, is targeted in the clinic for the treatment of systemic lupus erythematosus (SLE). The soluble form of BAFF can exist as 3-mer, or as 60-mer that results from the ordered assembly of twenty 3-mers and that can be obtained from naturally cleaved membrane-bound BAFF or made as a recombinant protein. However, which forms of soluble BAFF exist and act in humans is unclear. In this study, BAFF 3-mer and 60-mer in biological fluids were characterized for size, activity and response to specific stimulators or inhibitors of BAFF. Human cerebrospinal fluids (CSF) from patients with multiple sclerosis and adult human sera contained exclusively BAFF 3-mer in these assays, also when BAFF concentrations were moderately SLE or highly (BAFFR-deficient individual) increased. Human sera, but not CSF, contained a high molecular weight, saturable activity that dissociated preformed recombinant BAFF 60-mer into 3-mer. This activity was lower in cord blood. Cord blood displayed BAFF levels 10-fold higher than in adults and consistently contained a fair proportion of active high molecular weight BAFF able to dissociate into 3-mer but not endowed with all properties of recombinant BAFF 60-mer. If BAFF 60-mer is produced in humans, it is dissociated, or at least attenuated in the circulation.MicroRNAs (miRNAs) play a pivotal role in cartilage development and homeostasis in osteoarthritis (OA). While the fundamental roles of miRNAs in cartilage degeneration have been extensively studied, their effects on chondrogenic differentiation induced by human adipose-derived stem cells (hADSCs) and the underlying mechanisms remain largely elusive. Here, we investigated the roles and mechanisms of miRNAs in hADSC chondrogenic differentiation and chondrocyte homeostasis. Using microarray analysis, we screened miRNAs expressed in the chondrogenic differentiated hADSCs and identified miR-490-5p as the most significantly down-regulated miRNA. We analyzed its expression patterns during chondrogenesis in vivo and in vitro. Our study showed that miR-490-5p overexpression promoted the transition of hADSCs from chondrogenesis to osteogenesis. In addition, based on miRNA-mRNA prediction analysis and dual-luciferase reporter assay, we proposed and proved that miR-490-5p targeted PITPNM1 by binding to its 3'-UTR and inhibiting its translation. Moreover, loss- and gain-of-function experiments identified the involvement of the PI3K/AKT signaling pathway, and a rescue experiment determined the effect and specific mechanism of the miR-490-5p/PITPNM1/PI3K/AKT axis in hADSC chondrogenic differentiation and chondrocyte homeostasis. Inhibition of miR-490-5p alleviated cartilage injury in vivo as demonstrated using the destabilization of the medial meniscus (DMM) OA model. We identified miR-490-5p as a novel modulator of hADSC-mediated chondrogenesis and chondrocyte phenotype. This study highlighted that miR-490-5p attenuated hADSC chondrogenesis and accelerated cartilage degradation through activation of the PI3K/AKT signaling pathway by targeting PITPNM1. Inhibition of miR-490-5p facilitated hADSC chondrogenic differentiation and protected chondrocyte phenotype via the PITPNM1/PI3K/AKT axis, thus providing a novel stem cell potential therapeutic target for OA treatment.Neurodegeneration in Alzheimer's disease (AD) results in microglial activation, which may participate in the inflammatory cascade accelerating tissue damage. In this study, we sought to characterize the alleviatory role of microRNA-711 (miR-711) encapsulated in microglia-derived extracellular vesicles (EVs) in a model of AD. https://www.selleckchem.com/products/ha130.html Ultracentrifugation was employed to extract EVs from microglia (BV2 cells), which were identified using Western blot analysis of the EVs marker proteins Alix and CD63. A repetitive mild traumatic brain injury (rmTBI) mouse model was induced by controlled cortical impact. After overexpressing miR-711 or 1,4,5-trisphosphate 3-kinase B (Itpkb) in BV2 cells, we evaluated the inflammation in BV2 cells and the ratio of microglia M2/M1. Further, we injected BV2 cell-secreted EVs with overexpressed miR-711 or Itpkb into rmTBI mice through a tail vein to investigate the inflammation markers in mouse serum and, the M2/M1 phenotype ratio of microglia in brain tissues, and to evaluate neurological deficit and cognitive function. The EVs obtained by ultracentrifugation were verified by the presence of Alix and CD63 expression. Mechanistic studies suggested that miR-711 targeted and inhibited Itpkb, thereby repressing Tau phosphorylation and increasing the ratio of M2/M1. Furthermore, miR-711-containing EVs reduced the score of neurological deficits and improved cognitive function in rmTBI mice. The administration of microglia-derived EVs loaded with miR-711, which mediated the hyperphosphorylation of Tau protein in the Itpkb pathway, effectively alleviated neurodegenerative changes and cognitive dysfunction in AD.The mechanistic target of Rapamycin (mTOR) is essential for multiple cellular processes. The unique roles of mTOR complex 1 (mTORC1) or mTOR2 in regulating immune functions are emerging. NK cells are the major lymphocyte subset of innate immunity, and their development and effector functions require metabolic reprogramming. Recent studies demonstrate that in NK cells, conditionally disrupting the formation of mTORC1 or mTOR complex 2 (mTORC2) alters their development significantly. Transcriptomic profiling of NK cells at the single-cell level demonstrates that mTORC1 was critical for the early developmental progression, while mTORC2 regulated the terminal maturation. In this review, we summarize the essential roles of mTOR complexes in NK development and functions.Skeletal muscle and bone are highly interrelated, and previous proteomic analyses suggest that lumican is one of muscle-derived factors. To further understand the role of lumican as a myokine affecting adjacent bone metabolism, we investigated the effects of lumican on osteoblast biology. Lumican expression was significantly higher in the cell lysates and conditioned media (CM) of myotubes than those of undifferentiated myoblasts, and the known anabolic effects of myotube CM on osteoblasts were reduced by excluding lumican from the CM. Lumican stimulated preosteoblast viability and differentiation, resulting in increased calvaria bone formation. The expression of osteoblast differentiation markers was consistently increased by lumican. Lumican increased the phosphorylation of ERK, whereas ERK inhibitors completely reversed lumican-mediated stimulation of Runx2 and ALP activities in osteoblasts. Results of a binding ELISA experiment in osteoblasts show that transmembrane integrin α2β1 directly interacted with lumican, and an integrin α2β1 inhibitor attenuated the stimulation of ERK and ALP activities by lumican.