macrophages

摘要： Chronic spinal cord compression(CSCC)is induced by disc herniation and other reasons,leading to movement and sensation dysfunction,with a serious impact on quality of life.Spontaneous disc herniation rarely occurs in rodents,and therefore establishing a chronic spinal cord compression(CSCC)animal model is of crucial importance to explore the pathogenesis and treatment of CSCC.The absence of secreted protein,acidic,and rich in cysteine(SPARC)leads to spontaneous intervertebral disc degeneration in mice,which resembles human disc degeneration.In this study,we evaluated whether SPARC-null mice may serve as an animal model for CSCC.We performed rod rotation test,pain threshold test,gait analysis,and Basso Mouse Scale score.Our results showed that the motor function of SPARC-null mice was weakened,and magnetic resonance images revealed compression at different spinal cord levels,particularly in the lumbar segments.Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes,activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype;it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway.Notably,these findings are characteristics of CSCC.Therefore,we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.

摘要： Studies have shown that human hair keratin(HHK) has no antigenicity and excellent mechanical properties. Schwann cells, as unique glial cells in the peripheral nervous system, can be induced by interleukin-1β to secrete nerve growth factor, which promotes neural regeneration. Therefore, HHK with Schwann cells may be a more effective approach to repair nerve defects than HHK without Schwann cells. In this study, we established an artificial nerve graft by loading an HHK skeleton with activated Schwann cells. We found that the longitudinal HHK microfilament structure provided adhesion medium, space and direction for Schwann cells, and promoted Schwann cell growth and nerve fiber regeneration. In addition, interleukin-1β not only activates Schwann cells, but also strengthens their activity and increases the expression of nerve growth factors. Activated Schwann cells activate macrophages, and activated macrophages secrete interleukin-1β, which maintains the activity of Schwann cells. Thus, a beneficial cycle forms and promotes nerve repair. Furthermore, our studies have found that the newly constructed artificial nerve graft promotes the improvements in nerve conduction function and motor function in rats with sciatic nerve injury, and increases the expression of nerve injury repair factors fibroblast growth factor 2 and human transforming growth factor B receptor 2. These findings suggest that this artificial nerve graft effectively repairs peripheral nerve injury.

摘要： Recently,we read with interest the article entitled“Unveiling the Morphogenetic Code:A New Path at the Intersection of Physical Energies and Chemical Signaling”.In this paper,the investigation into the systematic and comprehensive bio-effects of physical energies prompted us to reflect on our research.We believe that ultrasound,which possesses a special physical energy,also has a certain positive regulatory effect on macrophages,and we have already obtained some preliminary research results that support our hypothesis.

摘要： Nuclear receptor subfamily 4 group A1(NR4A1)is an orphan nuclear receptor,which is expressed in the majority of cells.NR4A1 expression in peripheral blood mononuclear cells is low during the preclinical stage of multiple sclerosis.Knockout of the Nr4a1 gene in mice can aggravate the symptoms of experimental autoimmune encephalomyelitis(EAE),which is an animal model of multiple sclerosis.In this study,we intragastrically administered the NR4A1 agonist cytosporone B(Csn-B)to mice after inducing EAE.After treatment with Csn-B,the clinical symptoms in the EAE mice were substantially attenuated compared with that in PBS-treated control mice.The percentages of CD4+T cells and F4/80+cells in the central nervous system were decreased.In addition,interferon-γand interleukin-17 production by proinflammatory Th1/Th17 cells in the central nervous system and interferon-γlevels in splenocytes were decreased after Csn-B treatment.These findings suggest that the NR4A1 agonist Csn-B can alleviate nerve injury after EAE induction,and,therefore,may be useful as a potential treatment for multiple sclerosis.

摘要： Innate immune cells are critical for transplant response.As an important cellular component of innate immune cells,macrophages are the predominate infiltrated cells in allografts,and macrophage accumulation in allografts is negatively associated with the short-and long-term outcomes of organ transplantation.Macrophages are functionally heterogeneous and plastic.They participate in organ graft rejection through multiple pathways,including antigen presentation,the expression of costimulatory molecules and cytokines,and direct cytotoxicity and injury ability to allografts.However,some macrophage subpopulations,such as regulatory macrophages,can protect allografts from immune rejection and promote transplant immune tolerance with their immune regulatory properties.Although researchers recognize the potential roles macrophages play in allograft injury,they pay insufficient attention to the diverse roles of macrophages in allograft rejection.We herein briefly summarize the distinctive roles of macrophages in acute transplant immune response and the effect of immunosuppressive drugs on macrophages.Greater attention should be paid to the complex and critical function of macrophages in allograft rejection,and more effort should be put into developing immunosuppressive drugs that specifically target macrophages,which would ultimately improve the long-term survival of organ grafts in patients.

摘要： Pathologic inflammatory conditions are frequently correlated with dynamic alterations through macrophage activation,with classically activated Ml cells associated with promoting and sustaining inflammation and M2 cells implicated in resolving or smoldering chronic inflammation.Inflammation is a common feature of various chronic diseases,and it has direct involvement in the emergence and progression of these conditions.Macrophages participate in an autoregulatory loop characterizing inflammatory process,as they produce a wide range of biologically active mediators that exert either deleterious or beneficial effects during inflammation.Therefore,balancing the ratio of M1/M2 macrophages can help to ameliorate the inflammatory landscape of pathological conditions.This review will explore the role of macrophage polarization in distant pathological inflammatory conditions,such as cancer,autoimmunity,renal inflammation,stroke,and atherosclerosis,while sharing macrophage-driven pathogenesis.

摘要： Colorectal cancer(CRC)is the second deadliest malignancy for both sexes.The BRAF^(V600E)mutation,one of the most common driver mutations in CRC,is known for its poor prognosis due to the increased risk of metastasis.The effect of the BRAF^(V600E)mutation on the tumor microenvironment was the topic of the study reported in World Journal of Gastrointestinal Oncology,with special focus on immune status.The authors presented insightful findings that were exclusively based on macrophage polarity and cytokine levels,without investigating other relevant immune elements.A more comprehensive look into the dynamic immune activity of cancer environments will warrant more meaningful practical findings.In this letter,we discuss other significant immune factors and their possible implications on the tumor microenvironment of BRAF-mutated CRC.

摘要： Atherosclerosis is a fundamental pathological change in coronary heart disease,with vulnerable plaque formation leading to decreased plaque stability and plaque rupture,and is a major cause of acute cardiovascular events.The inflammatory response is an important mechanism in the development and progression of atherosclerosis,and plaque stability is closely related to the inflammatory response.In recent years,the role of NLRP3 inflammatory vesicles,which are involved in macrophage foaminess,in the inflammatory response to atherosclerosis has received increasing attention.Chinese medicine is able to modulate inflammatory vesicles to improve atherosclerotic plaque stability,showing good promise in the prevention and treatment of atherosclerotic vulnerable plaques.Based on the role of inflammatory vesicles in atherosclerosis and the results of previous studies that wind-extinguishing and phlegm-resolving medicine can effectively modulate the inflammatory response to intervene in the treatment of atherosclerosis,this paper aims to investigate the treatment of coronary atherosclerosis by wind-extinguishing and phlegm-resolving medicine from the direction of inflammatory vesicles.

摘要： MiRNAs and macrophages play important roles in renal fibrosis.The exosomes secreted by bone marrow mesenchymal stem cells(BM-MSCs)can alleviate renal fibrosis.What is not clear,however,is whether a type of miRNAs in the BM-MSCs exosomes can alleviate renal fibrosis by modulating macrophage polarization.First,we take a high-throughput sequencing of miRNAs in exo­somes of BM-MSCs from chronic kidney disease(CKD)and normal people.Then we used the UUO mouse model and injected exosomes into the tail vein.The macrophages were stimulated with lipopolysaccharide(LPS).MSC-Exo or exosomes from BM-MSCs transfected with miR-93-5p inhibitor(Inhi-Exo)were added to the culture medium.The macrophages were transfected with miR-93-5p inhibitor or miR-93-5p mimic alone.The expression of miR-93-5p in exosomes of CKD patients was significantly decreased compared with normal people and in the LPS-stimulated macrophages and UUO mice kidneys.After stimulation with LPS,the macrophages polarized toward M1 subtype.MSC-Exo or miR-93-5p mimic promoted macrophages from M1 to M2 sub­type.Inhi-Exo or miR-93-5p inhibitor blocked the differentiation from M1 to M2 subtype.Significant fibrotic changes occurred in the kidneys of UUO mice,and M1 macrophages were significantly increased.After injecting exosomes into the tail vein of UUO mice,the degree of renal fibrosis was alleviated,the expression of miR-93-5p in the kidney was significantly increased,and the renal macrophages differentiated from M1 to M2 subtype.These results demonstrated that miR-93-5p in the exosomes derived from BM-MSCs can improve renal fibrosis by inducing macrophage differentiation from M1 to M2 subtype.

摘要： The development of polycystic ovary syndrome(PCOS)is closely related to the chronic inflammatory and obese.Recent studies have found macrophages regulate the chronic inflammation and adipose tissue remodelling,but the underlying mechanisms have not been clarified.In this study,we established a model of PCOS in the offspring rats by high androgen exposure during late pregnancy in parental and established a female rat macrophage eliminating model by rejection of clodronate liposome.Then,the offspring rat macrophage phenotype in offspring female rat adipose tissue,and levels of testosterone,angiogenic factors(PDGF and VEGF)and inflammatory factors(TNF-αand MCP-1)were investigated.By coculture of RAW264.7 macrophage with adipocytes or C166 endothelial cells(ECs),the mobility of adipocytes,and the ECs function with associated signalling pathway were detected by using of androgen inhibitor Apalutamide,NF-κB inhibitor JSH-23 and ERK1/2 inhibitor LY3214996.It was found that high androgen exposure during late pregnancy led to increased testosterone levels and overweight and obesity,increased size and reduced number of subcutaneous and intra-abdominal adipocytes,and increased secretion of TNF-αand MCP-1 in female rats in the offspring.Eliminating macrophages significantly increased adipocytes and angiogenesis in offspring of rats with intrauterine high androgen,and reduced TNF-αand MCP-1.Macrophages promoted mobility of adipocytes,and inhibited proliferation,migration,tube formation of ECs under hyperandrogenic condition,which were significantly inhibited by Apalutamide,JSH-23 and LY3214996.Thus,intrauterine high androgen promotes obesity of the offspring of rats with polycystic ovarian syndrome through increasing M1 differentiation of pro-inflammatory macrophages and activating VEGF-related angiogenesis via androgen/NF-κB/ERK1/2 signalling pathway.