A pathological joint-liver axis mediated by matrikine-activated CD4+ T cells.

The knee joint has long been considered a closed system. The pathological effects of joint diseases on distant organs have not been investigated. Herein, our clinical data showed that post-traumatic joint damage, combined with joint bleeding (hemarthrosis), exhibits a worse liver function compared with healthy control. With mouse model, hemarthrosis induces both cartilage degeneration and remote liver damage. Next, we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4+ T cells in peripheral blood and spleen. Deletion of CD4+ T cells reverses hemarthrosis-induced liver damage. Degeneration of cartilage matrix induced by hemarthrosis upregulates serological type II collagen (COL II), which activates CD4+ T cells. Systemic application of a COL II antibody blocks the activation. Furthermore, bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood treatment. Intra-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig models. Taken together, our study revealed a pathological joint-liver axis mediated by matrikine-activated CD4+ T cells, which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease. Intra-articular bleeding induces cartilage degradation through down-reulation of cartilage Akt pathway. During this process, the soluble COL II released from the damaged cartilage can activate peripheral CD4+ T cells, differention into Th17 cells and secretion of IL-17, which consequently induces liver impairment. Intra-articular application of sc79 (inhibitor of Akt pathway) can prevent the cartilage damage as well as its peripheral influences.

Progress in research on effect of PM2.5 on occurrence and development of atherosclerosis.

Fine particulate matter ≤2.5 µm (PM2.5 ) air pollution is regarded as one of the prominent risk factors that contributes to morbidity and mortality globally, among which cardiovascular disease (CVD) has been strongly associated with PM2.5 exposure and is a leading cause of death. Atherosclerosis (AS), the common pathological basis of many CVDs, is a progressive syndrome characterized by the accumulation of lipids and fibrous plaque in the arteries. Recent epidemiological and toxicological studies suggest that PM2.5 may also contribute to the development of AS, even at levels below the current air quality standards. In this paper, the complete pathological process of atherosclerotic plaque from occurrence to rupture leading to CVD was elaborated. Then, the growing epidemiological evidence linking PM2.5 to AS in humans was reviewed and summarized. Furthermore, the potential mechanisms of PM2.5 -mediated AS were discussed, including oxidative stress, inflammation, endothelial dysfunction, abnormal lipid metabolism, disturbance of the autonomic nervous system, and abnormal coagulation function. This paper aimed to provide a comprehensive view of the effect of PM2.5 on the occurrence and development of AS for better prevention and mitigation of adverse health impacts due to PM2.5 air pollution.

Validation of PM2.5 model particle through physicochemical evaluation and atherosclerotic plaque formation in ApoE-/- mice.

PM2.5 particles are regarded as prominent risk factors that contribute to the development of atherosclerosis. However, the composition of PM2.5 is rather complicated. This study aimed to provide a model particle that simulates the behavior of actual PM2.5, for subsequent use in exploring mechanisms and major complications arising from PM2.5. To establish model particles of PM2.5, a series of monodisperse SiO2 microspheres with different average grain diameters were mixed according to the size distribution of actual PM2.5. The organic carbon (OC) was removed from PM2.5 and coated onto the SiO2 model particle, to formulate simulant PM2.5. Results showed that the size distribution of the model particle was highly approximate to that of the PM2.5 core. The polycyclic aromatic hydrocarbon (PAHs) composition profile of the simulated PM2.5 were approximate to PM2.5, and loading efficiency was approximately 80%-120%. Furthermore, compared to the control, SiO2-only model particle had negligible cytotoxicity on cell viability and oxidative stress of HUVECs, and marginal effect on the lipid metabolism and atherosclerotic plaque formation in ApoE-/- mice. In contrast, simulated PM2.5 exhibited similar cytotoxic and detrimental effects on lipid metabolism and atherosclerotic plaque formation with actual PM2.5. Traffic-related PM2.5 had negative effects on endothelial function and led to the formation of atherosclerosis via oxidative stress. The simulated PM2.5 simulated the outcomes of actual PM2.5 exposure. Here, we show that SiO2 particle model cores coated with OC could significantly assist in the evaluation of the effects of specific organic compositions bound on PM2.5, specifically in the context of environmental health and safety.

Understanding the Immunological Mechanisms of Mesenchymal Stem Cells in Allogeneic Transplantation: From the Aspect of Major Histocompatibility Complex Class I.

Mesenchymal stem cell (MSC) transplantation therapy appears to be an ideal strategy for repairing structural defects and restoring the functions of diseased tissues and organs. Additionally, MSCs are also used as immunosuppressants in allogeneic organ transplantation. However, owing to their inherent immunogenicity, MSC transplantation can induce the activation of an immune response, which can lead to the death and clearance of the transplanted MSCs. Major histocompatibility complex (MHC) molecules are responsible for antigen presentation, help T lymphocytes to recognize endogenous/extrinsic antigens, and trigger immune activation. Many studies have shown that MHC molecules (particularly class I) play key roles in the immunogenicity of MSCs. This review, therefore, focuses on the relationship between MHC-I surface expression on MSCs and its immunogenicity, as well as potential strategies to overcome the hurdle of MHC incompatibility.

Regulation of Inflammatory Cytokines for Spinal Cord Injury Repair Through Local Delivery of Therapeutic Agents.

The balance of inflammation is critical to the repair of spinal cord injury (SCI), which is one of the most devastating traumas in human beings. Inflammatory cytokines, the direct mediators of local inflammation, have differential influences on the repair of the injured spinal cord. Some inflammatory cytokines are demonstrated beneficial to spinal cord repair in SCI models, while some detrimental. Various animal researches have revealed that local delivery of therapeutic agents efficiently regulates inflammatory cytokines and promotes repair from SCI. Quite a few clinical studies have also shown the promotion of repair from SCI through regulation of inflammatory cytokines. However, local delivery of a single agent affects only a part of the inflammatory cytokines that need to be regulated. Meanwhile, different individuals have differential profiles of inflammatory cytokines. Therefore, future studies may aim to develop personalized strategies of locally delivered therapeutic agent cocktails for effective and precise regulation of inflammation, and substantial functional recovery from SCI.