Targeting neuroinflammation is a novel frontier in the prevention and treatment of epilepsy. A substantial body of evidence supports a key role for neuroinflammation in epileptogenesis, the pathological process that leads to the development and progression of spontaneous recurrent epileptic seizures. It is also well recognized that traumatic brain injury (TBI) induces a vigorous neuroinflammatory response and that a significant proportion of patients with TBI suffer from debilitating post-traumatic epilepsy. The complement system is a potent effector of innate immunity and a significant contributor to secondary tissue damage and to epileptogenesis following central nervous system injury. Several therapeutic agents targeting the complement system are already on the market to treat other central nervous system disorders or are well advanced in their development. The purpose of this review is to summarize findings on complement activation in experimental TBI and epilepsy models, highlighting the potential of drug repurposing in the development of therapeutics to ameliorate post-traumatic epileptogenesis.After intra-articular injection, synovium-derived mesenchymal stem cells (SMSCs) can adhere to damaged cartilage (a process called homing) and then repair the cartilage defect. Nonetheless, the main obstacle of the current method is the insufficient homing ratio of SMSCs, which fails to meet the requirements for cartilage repair and thereby greatly limits the therapeutic effect. In this study, the optimal homing time of SMSCs was determined by evaluating the SMSCs homing efficiency at 1, 3, 7, 14, and 28 d after injury using a rat cartilage defect model. The ability of platelet-derived microparticles (PMPs) to promote SMSCs homing was evaluated by cartilage/subchondral bone cell adhesion, transmembrane migration and intra-articular cell distribution assays. SMSCs had an optimal homing efficiency in the very early stage (1 d) after cartilage injury. We found that PMPs, which were abundant in the synovial fluid (SF) at this early stage, were responsible for this augmented SMSCs homing. An ex vivo cell adhesion assay revealed that the coincubation of SMSCs with PMPs at a 150 ratio markedly enhanced cell adhesion to cartilage and the subchondral bone surface. The transmembrane cell migration assay yielded similar results. Further in vivo homing assays revealed that PMPs possess excellent homing capacity, which they transferred, to some extent, to SMSCs by coating the cell surface. We measured the expression of homing-related genes in SMSCs exposed to PMPs and identified several upregulated genes. Moreover, platelet-specific adhesion molecules, particularly GPIIb/IIIa, CXCR4, ITGβ1, and ITGα2, were determined to play a critical role in the homing of SMSC/PMP complexes.  https://www.selleckchem.com/products/ag-221-enasidenib.html  This improvement in SMSCs homing increased the volume of regenerated tissue in the cartilage defect. In conclusion, PMPs significantly promoted the homing of SMSCs to cartilage, which facilitated cartilage regeneration. These data suggest a safe and promising strategy for improving the outcome of stem cell therapy.Background Pressure overload of the heart occurs in patients with hypertension or valvular stenosis and induces cardiac fibrosis because of excessive production of extracellular matrix by activated cardiac fibroblasts. This initially provides essential mechanical support to the heart, but eventually compromises function. Osteopontin is associated with fibrosis; however, the underlying signaling mechanisms are not well understood. Herein, we examine the effect of thrombin-cleaved osteopontin on fibrosis in the heart and explore the role of syndecan-4 in regulating cleavage of osteopontin. Methods and Results Osteopontin was upregulated and cleaved by thrombin in the pressure-overloaded heart of mice subjected to aortic banding. Cleaved osteopontin was higher in plasma from patients with aortic stenosis receiving crystalloid compared with blood cardioplegia, likely because of less heparin-induced inhibition of thrombin. Cleaved osteopontin and the specific osteopontin peptide sequence RGDSLAYGLR that is exposed after thrombin cleavage both induced collagen production in cardiac fibroblasts. Like osteopontin, the heparan sulfate proteoglycan syndecan-4 was upregulated after aortic banding. Consistent with a heparan sulfate binding domain in the osteopontin cleavage site, syndecan-4 was found to bind to osteopontin in left ventricles and cardiac fibroblasts and protected osteopontin from cleavage by thrombin. Shedding of the extracellular part of syndecan-4 was more prominent at later remodeling phases, at which time levels of cleaved osteopontin were increased. Conclusions Thrombin-cleaved osteopontin induces collagen production by cardiac fibroblasts. Syndecan-4 protects osteopontin from cleavage by thrombin, but this protection is lost when syndecan-4 is shed in later phases of remodeling, contributing to progression of cardiac fibrosis.The canalicular system (CS) has been defined as 1) an inward, invaginated membrane connector that supports entry into and exit from the platelet; 2) a static structure stable during platelet isolation; and 3) the major source of plasma membrane (PM) for surface area expansion during activation. Recent analysis from STEM tomography and serial block face electron microscopy has challenged the relative importance of CS as the route for granule secretion. Here, We used 3D ultrastructural imaging to reexamine the CS in mouse platelets by generating high-resolution 3D reconstructions to test assumptions 2 and 3. Qualitative and quantitative analysis of whole platelet reconstructions, obtained from immediately fixed or washed platelets fixed post-washing, indicated that CS, even in the presence of activation inhibitors, reorganized during platelet isolation to generate a more interconnected network. Further, CS redistribution into the PM at different times, post-activation, appeared to account for only about half the PM expansion seen in thrombin-activated platelets, in vitro, suggesting that CS reorganization is not sufficient to serve as a dominant membrane reservoir for activated platelets. In sum, our analysis highlights the need to revisit past assumptions about the platelet CS to better understand how this membrane system contributes to platelet function.