Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance...Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.展开更多
Background:The aim was to explore the effect of macrophage polarization and macrophage-to-myofibroblast transition(MMT)in silicosis.Methods:Male Wistar rats were divided into a control group and a silicosis group deve...Background:The aim was to explore the effect of macrophage polarization and macrophage-to-myofibroblast transition(MMT)in silicosis.Methods:Male Wistar rats were divided into a control group and a silicosis group developed using a HOPE MED 8050 dynamic automatic dusting system.Murine mac-rophage MH-S cells were randomly divided into a control group and an SiO_(2) group.The pathological changes in lung tissue were observed using hematoxylin and eosin(HE)and Van Gieson(VG)staining.The distribution and location of macrophage marker(F4/80),M1 macrophage marker(iNOS),M2 macrophage marker(CD206),and myofibroblast marker(α-smooth muscle actin[α-SMA])were detected using immu-nohistochemical and immunofluorescent staining.The expression changes in iNOS,Arg,α-SMA,vimentin,and type I collagen(Col I)were measured using Western blot.Results:The results of HE and VG staining showed obvious silicon nodule formation and the distribution of thick collagen fibers in the lung tissue of the silicosis group.Macrophage marker F4/80 increased gradually from 8 to 32 weeks after exposure to silica.Immunohistochemical and immunofluorescent staining results revealed that there were more iNOS-positive cells and some CD206-positive cells in the lung tissue of the silicosis group at 8 weeks.More CD206-positive cells were found in the silicon nodules of the lung tissues in the silicosis group at 32 weeks.Western blot analysis showed that the expressions of Inducible nitric oxide synthase and Arg protein in the lung tissues of the silicosis group were upregulated compared with those of the con-trol group.The results of immunofluorescence staining showed the co-expression of F4/80,α-SMA,and Col I,and CD206 andα-SMA were co-expressed in the lung tissue of the silicosis group.The extracted rat alveolar lavage fluid revealed F4/80+α-SMA+,CD206+α-SMA+,and F4/80+α-SMA+Col I+cells using immunofluorescence staining.Similar results were also found in MH-S cells induced by SiO_(2).Conclusions:The development of silicosis is accompanied by macrophage polarization and MMT.展开更多
BACKGROUND Macrophages play a crucial role in the tumor microenvironment,displaying remarkable plasticity that allows them to either suppress or promote tumor progression.Their polarization into M1 or M2 phenotypes co...BACKGROUND Macrophages play a crucial role in the tumor microenvironment,displaying remarkable plasticity that allows them to either suppress or promote tumor progression.Their polarization into M1 or M2 phenotypes could have significant prognostic implications,and manipulating this polarization may offer a novel approach to controlling colorectal neoplasms.AIM To evaluate the infiltration rates of M1 and M2 macrophages in colorectal neoplasia,specifically comparing cases with and without metalloproteinase mutations.Additionally,it sought to explore potential prognostic factors as-sociated with the disease.展开更多
BACKGROUND Macrophages are central to the orchestration of immune responses,inflammatory processes,and the pathogenesis of diabetic complications.The dynamic polarization of macrophages into M1 and M2 phenotypes criti...BACKGROUND Macrophages are central to the orchestration of immune responses,inflammatory processes,and the pathogenesis of diabetic complications.The dynamic polarization of macrophages into M1 and M2 phenotypes critically modulates inflammation and contributes to the progression of diabetic nephropathy.Sodiumglucose cotransporter 2 inhibitors such as dapagliflozin,which are acclaimed for their efficacy in diabetes management,may influence macrophage polarization,thereby ameliorating diabetic nephropathy.This investigation delves into these mechanistic pathways,aiming to elucidate novel therapeutic strategies for diabetes.AIM To investigate the inhibitory effect of dapagliflozin on macrophage M1 polarization and apoptosis and to explore its mechanism of action.METHODS We established a murine model of type 2 diabetes mellitus and harvested peritoneal macrophages following treatment with dapagliflozin.Concurrently,the human monocyte cell line cells were used for in vitro studies.Macrophage viability was assessed in a cell counting kit 8 assay,whereas apoptosis was evaluated by Annexin V/propidium iodide staining.Protein expression was examined through western blotting,and the expression levels of macrophage M1 surface immunosorbent assay,and quantitative real-time polymerase chain reaction analyses.RESULTS Dapagliflozin attenuated M1 macrophage polarization and mitigated apoptosis in the abdominal macrophages of diabetic mice,evidenced by the downregulation of proapoptotic genes(Caspase 3),inflammatory cytokines[interleukin(IL)-6,tumor necrosis factor-α,and IL-1β],and M1 surface markers(inducible nitric oxide synthase,and cluster of differentiation 86),as well as the upregulation of the antiapoptotic gene BCL2.Moreover,dapagliflozin suppressed the expression of proteins associated with the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway(PI3K,AKT,phosphorylated protein kinase B).These observations were corroborated in vitro,where we found that the modulatory effects of dapagliflozin were abrogated by 740Y-P,an activator of the PI3K/AKT signaling pathway.CONCLUSION Dapagliflozin attenuates the polarization of macrophages toward the M1 phenotype,thereby mitigating inflammation and promoting macrophage apoptosis.These effects are likely mediated through the inhibition of the PI3K/AKT signaling pathway.展开更多
Liver cancer,and in particular hepatocellular carcinoma(HCC)is a disease of rising prevalence and incidence.To date,definitive treatment options include either surgical excision or ablation of the affected area.With i...Liver cancer,and in particular hepatocellular carcinoma(HCC)is a disease of rising prevalence and incidence.To date,definitive treatment options include either surgical excision or ablation of the affected area.With increasing research on several pathways that could be involved in the progression of HCC,new elements within these pathways emerge as potential targets for novel therapies.The WNT/β-catenin pathway favors the presence of M2 tumor-associated macrophages which in turn promote tumor growth and metastasis.The inhibition of this pathway is considered a good candidate for such targeted therapeutic interventions.Interestingly,as Huang et al show in their recently published article,Calculus bovis which is used in traditional Chinese medicine can exert an inhibitory effect on theβ-catenin pathway and become a potential candidate for targeted pharmacotherapy against liver cancer.展开更多
BACKGROUND Mesenchymal stem cells,found in various tissues,possess significant healing and immunomodulatory properties,influencing macrophage polarization,which is essential for wound repair.However,chronic wounds pre...BACKGROUND Mesenchymal stem cells,found in various tissues,possess significant healing and immunomodulatory properties,influencing macrophage polarization,which is essential for wound repair.However,chronic wounds present significant therapeutic challenges,requiring novel strategies to improve healing outcomes.AIM To investigate the potential of fetal dermal mesenchymal stem cells(FDMSCs)in enhancing wound healing through modulation of macrophage polarization,specifically by promoting the M2 phenotype to address inflammatory responses in chronic wounds.METHODS FDMSCs were isolated from BalB/C mice and co-cultured with RAW264.7 macrophages to assess their effects on macrophage polarization.Flow cytometry,quantitative reverse transcriptase polymerase chain reaction,and histological analyses were employed to evaluate shifts in macrophage phenotype and wound healing in a mouse model.Statistical analysis was performed using GraphPad Prism.RESULTS FDMSCs induced macrophage polarization from the M1 to M2 phenotype,as demonstrated by a reduction in proinflammatory markers(inducible nitric oxide synthase,interleukin-6)and an increase in anti-inflammatory markers[mannose receptor(CD206),arginase-1]in co-cultured RAW264.7 macrophages.These shifts were confirmed by flow cytometry.In an acute skin wound model,FDMSC-treated mice exhibited faster wound healing,enhanced collagen deposition,and improved vascular regeneration compared to controls.Significantly higher expression of arginase-1 further indicated an enriched M2 macrophage environment.CONCLUSION FDMSCs effectively modulate macrophage polarization from M1 to M2,reduce inflammation,and enhance tissue repair,demonstrating their potential as an immunomodulatory strategy in wound healing.These findings highlight the promising therapeutic application of FDMSCs in managing chronic wounds.展开更多
Background : To study the relationships among emodin, synovial fibroblasts (FLSs), and macrophages (STMs) to provide guidance for the use of emodin in rheumatoid arthritis (RA) treatment. Methods : RA clinical samples...Background : To study the relationships among emodin, synovial fibroblasts (FLSs), and macrophages (STMs) to provide guidance for the use of emodin in rheumatoid arthritis (RA) treatment. Methods : RA clinical samples from patients with different pathological processes were collected, and the correlations between the subsets of FLSs and STMs and pathological processes were analyzed via flow cytometry. In vitro experimental methods such as enzyme linked immunosorbent assay (ELISA), Western blotting, Transwell assays, CCK- 8 assays and cell coculture were used to assess cell proliferation, migration and secretion of inflammatory factors. A collagen- induced arthritis mouse model was constructed to investigate the therapeutic potential of emodin in RA by flow cytometry, micro- CT and staining. Results : Unique subsets of FLSs and STMs, namely, FAPα ^(+)THY1 − FLSs, FAPα ^(+)THY1 ^(+)FLSs, and MerTK ^(pos) TREM2 ^(high) STMs, were identified in synovial tissues from RA patients. The number of MerTK ^(pos) TREM2 ^(high) STMs was negatively correlated with the degree of damage in RA, while the number of FAPα ^(+)THY1 − FLSs was positively correlated with damage. On the one hand, emodin promoted the aggregation of MerTKposTREM2high STMs. Moreover, MerTK pos TREM2 high STM- mediated secretion of exosomes was promoted, which can inhibit the secretion of pro- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs and promote the secretion of anti- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs, thereby inhibiting FAPα ^(+)THY1 − FLS proliferation and migration, improving the local immune microenvironment, and inhibiting RA damage. Conclusion : Emodin was shown to regulate the aggregation of STM subsets and exosome secretion, affecting the secretion, proliferation and migration of inflammatory factors in FLS subsets, and ultimately achieving good therapeutic efficacy in RA patients, suggesting that it has important clinical value.展开更多
Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon(RAP).Despite its therapeutic effects,the surgical risk and unclear mechanism hamper th...Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon(RAP).Despite its therapeutic effects,the surgical risk and unclear mechanism hamper the clinical application.Numerous evidences support macrophages as the key immune cells during bone remodeling.Our study discovered that the monocyte-derived macrophages primarily exhibited a pro-inflammatory phenotype that dominated bone remodeling in corticotomy by CX3CR1CreERT2;R26GFP lineage tracing system.Fluorescence staining,flow cytometry analysis,and western blot determined the significantly enhanced expression of binding immunoglobulin protein(BiP)and emphasized the activation of sensor activating transcription factor 6(ATF6)in macrophages.Then,we verified that macrophage specific ATF6 deletion(ATF6f/f;CX3CR1CreERT2 mice)decreased the proportion of pro-inflammatory macrophages and therefore blocked the acceleration effect of corticotomy.In contrast,macrophage ATF6 overexpression exaggerated the acceleration of orthodontic tooth movement.In vitro experiments also proved that higher proportion of pro-inflammatory macrophages was positively correlated with higher expression of ATF6.At the mechanism level,RNA-seq and CUT&Tag analysis demonstrated that ATF6 modulated the macrophage-orchestrated inflammation through interacting with Tnfαpromotor and augmenting its transcription.Additionally,molecular docking simulation and dual-luciferase reporter system indicated the possible binding sites outside of the traditional endoplasmic reticulum-stress response element(ERSE).Taken together,ATF6 may aggravate orthodontic bone remodeling by promoting Tnfαtranscription in macrophages,suggesting that ATF6 may represent a promising therapeutic target for non-invasive accelerated orthodontics.展开更多
BACKGROUND Periodontitis,when exacerbated by diabetes,is characterized by increased M1 macrophage polarization and decreased M2 polarization.O-linkedβ-N-acetylglucosamine(O-GlcNAcylation),catalyzed by O-GlcNAc transf...BACKGROUND Periodontitis,when exacerbated by diabetes,is characterized by increased M1 macrophage polarization and decreased M2 polarization.O-linkedβ-N-acetylglucosamine(O-GlcNAcylation),catalyzed by O-GlcNAc transferase(OGT),promotes inflammatory responses in diabetic periodontitis(DP).Additionally,p38 mitogen-activated protein kinase regulates macrophage polarization.However,the interplay between OGT,macrophage polarization,and p38 signaling in the progression of DP remains unexplored.AIM To investigate the effect of OGT on macrophage polarization in DP and its role in mediating O-GlcNAcylation of p38.METHODS For in vivo experiments,mice were divided into four groups:Control,DP model,model+short hairpin(sh)RNAnegative control,and model+sh-OGT.Diabetes was induced by streptozotocin,followed by ligation and lipopolysaccharide(LPS)administration to induce periodontitis.The impact of OGT was assessed by injecting sh-OGT lentivirus.Maxillary bone destruction was evaluated using micro-computed tomography analysis and tartrateresistant acid phosphatase staining,while macrophage polarization was determined through quantitative real-time polymerase chain reaction(qPCR)and immunohistochemistry.For in vitro experiments,RAW264.7 cells were treated with LPS and high glucose(HG)(25 mmol/L D-glucose)to establish a cell model of DP.OGT was inhibited by OGT inhibitor(OSMI4)treatment and knocked down by sh-OGT transfection.M1/M2 polarization was analyzed using qPCR,immunofluorescence,and flow cytometry.Levels of O-GlcNAcylation were measured using immunoprecipitation and western blotting.RESULTS Our results demonstrated that M1 macrophage polarization led to maxillary bone loss in DP mice,associated with elevated O-GlcNAcylation and OGT levels.Knockdown of OGT promoted the shift from M1 to M2 macrophage polarization in both mouse periodontal tissues and LPS+HG-induced RAW264.7 cells.Furthermore,LPS+HG enhanced the O-GlcNAcylation of p38 in RAW264.7 cells.OGT interacted with p38 to promote its O-GlcNAcylation at residues A28,T241,and T347,as well as its phosphorylation at residue Y221.CONCLUSION Inhibition of OGT-mediated p38 O-GlcNAcylation deactivates the p38 pathway by suppressing its self-phosphorylation,thereby promoting M1 to M2 macrophage polarization and mitigating DP.These findings suggested that modulating macrophage polarization through regulation of O-GlcNAcylation may represent a novel therapeutic strategy for treating DP.展开更多
Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic m...Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic membrane(d AM)make it a subject of exploration for its potential impact on the anti-inflammatory response of macrophages.Experimental findings unequivocally demonstrate that d AM promotes anti-inflammatory M2 polarization of macrophage,with its cytokine-rich content posited as a potential mediator.The application of RNA sequencing unveils differential gene expression,implicating the hypoxia inducible factor-1α(HIF-1α)signaling pathway in this intricate interplay.Subsequent investigation further demonstrates that d AM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor(EGF),which,in turn,activates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway and stabilizes HIF-1α.This cascade results in a noteworthy augmentation of anti-inflammatory gene expression.This study significantly contributes to advancing our comprehension of d AM's immunomodulatory role in tissue repair,thereby suggesting promising therapeutic potential.展开更多
Objective:The occurrence and development of atrial fibrillation(AF)are influenced by the autonomic nervous system and inflammation.Acupuncture is an effective treatment for AF.This study explored the protective effect...Objective:The occurrence and development of atrial fibrillation(AF)are influenced by the autonomic nervous system and inflammation.Acupuncture is an effective treatment for AF.This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms.Methods:Male Sprague-Dawley rats(n=130)were randomly divided into blank control(Con),sham operation(Sham),AF,and acupuncture treatment(Acu)groups.A paroxysmal AF model was established by rapid atrial pacing through the jugular vein.Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint(PC6)for 20 min daily for seven days.The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture.The AF induction rate,AF duration,cardiac electrophysiological parameters,and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals.After the intervention,the rats were euthanized,and atrial morphology was assessed using haematoxylin and eosin staining.The expression of macrophage F4/80 antigen(F4/80)and cluster of differentiation(CD)86 in atrial myocardial tissue was detected using immunohistochemistry,immunofluorescence and flow cytometry.The expression levels or contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-a(TNF-a),a7 nicotinic acetylcholine receptor(a7nAChR),phosphorylated Janus kinase 2(p-JAK2),and phosphorylated signal transducer and activator of transcription 3(p-STAT3)in atrial myocardial tissue were detected using Western blotting,reverse transcription-quantitative polymerase chain reaction,or enzyme-linked immunosorbent assay.The role of a7nAChR in acupuncture treatment was verified by intraperitoneal injection of the a7nAChR antagonist methyllycaconitine(MLA).Results:Compared with the AF group,acupuncture significantly reduced AF duration and induction rate,improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance.It also decreased the pro-inflammatory M1 macrophage proportion,alleviating myocardial injury and infiltration.MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect.Results suggest that acupuncture triggers the a7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation.Conclusion:Acupuncture significantly reduced the AF induction rate,shortened AF duration,improved cardiac electrophysiological parameters,enhanced vagus nerve activity,and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)are a significant contributor to disability and mortality in diabetic patients.Macrophage polarization and functional regulation are promising areas of research and show therapeuti...BACKGROUND Diabetic foot ulcers(DFUs)are a significant contributor to disability and mortality in diabetic patients.Macrophage polarization and functional regulation are promising areas of research and show therapeutic potential in the field of DFU healing.However,the complex mechanism,the difficulty in clinical translation,and the large heterogeneity present significant challenges.Hence,this study was to comprehensively analyze the publication status and trends of studies on macrophage polarization and DFU healing.AIM To examine the relevant literature on macrophage polarization in DFU healing.METHODS A bibliometric analysis was conducted using the Web of Science database.Relevant literature was retrieved from the Web of Science Core Collection database between 2013 to 2023 using literature visualization and analysis software(VOSviewer and CiteSpace)and bibliometric online platforms.The obtained literature was then subjected to visualization and analysis of different countries/regions,institutions,journals,authors,and keywords to reveal the research’s major trends and focus.RESULTS The number of publications on the role of macrophage polarization in DFU healing increased rapidly from 2013 to 2023,especially in the latter period.Chinese researchers were the most prolific in this field,with 217 publications,while American researchers had been engaged in this field for a longer period.Qian Tan of Nanjing Drum Tower Hospital and Qian Ding of Nanjing University were the first to publish in this field.Shanghai Jiao Tong University was the institution with the most publications(27).The keywords“bone marrow”,“adjustment,replacement,response,tissue repair”,and“activation,repair,differentiation”appeared more frequently.The study of macrophage polarization in DFU healing focused on the regulatory mechanism,gene expression,and other aspects.CONCLUSION This study through the bibliometric method reveals the research trends and development trends in this field of macrophage polarization in DFU healing from 2013 to 2023 in the Web of Science Core Collection database.The key hotspots in this field mainly include the regulation of macrophage activation,gene expression,wound tissue repair,and new wound materials.This study provides references for future research directions.展开更多
Abnormal activation of macrophages and osteoclasts(OCs)contributes significantly to rheumatoid arthritis(RA)development by secretion of numerous inflammatory factors.Notably,these cells exhibit significant upregulatio...Abnormal activation of macrophages and osteoclasts(OCs)contributes significantly to rheumatoid arthritis(RA)development by secretion of numerous inflammatory factors.Notably,these cells exhibit significant upregulation of folate receptor proteins on their surfaces.Unfortunately,there is a current lack of safe and effective therapeutic drugs for RA.Xuetongsu(XTS),a triterpenoid compound extracted fromKadsura heteroclita Roxb Craib,has demonstrated the ability to significantly inhibit the proliferation of RA fibroblast-like synoviocytes(RAFLS).However,its clinical application is hampered by poor targeting and short half-life.To address these drawbacks,we previously developed a nano-drug system named HRPS nanoparticles(NPs),which effectively targets RAFLS and inhibits synovial hyperplasia.However,this system overlooked the essential role of OCs in RA-related bone destruction.Therefore,we designed a novel folate-modified biomimetic Prussian blue(PB)-XTS NP(FMPX NP)for the selective delivery of XTS into inflammatory macrophages and OCs.The NP exhibits an excellent photothermal effect when assisted by laser irradiation,facilitating targeted release of XTS within inflammatory macrophages and OCs.The synergistic anti-inflammatory and reactive oxygen species scavenging effects of PB NPs and XTS are mediated by the inhibition of the NF-κB signaling pathway in inflammatory macrophages and RANK/RANKL/NFATc1 signaling pathway in OCs.In vivo experiments showed that FMPX NPs extended the half-life of XTS by 2.32 times,decreased hind foot swelling from 12.10±0.49 mm to 8.24±0.09 mm in the model group,and prevented bone damage.In conclusion,this study introduces a novel dual-targeted nano-based therapy for RA joints and highlights its potential for biochemical photothermal triple therapy for RA.FMPX NPs inhibit arthritis-related inflammation and bone destruction through a dual-target strategy,providing new insights for targeted drug therapies in clinical RA treatment.展开更多
Lactobacillus species have excellent abilities to reduce intestinal inflammation and enhance gut barrier function.This study elucidated the potential mechanisms through which Lactobacillus mitigates lipopolysaccharide...Lactobacillus species have excellent abilities to reduce intestinal inflammation and enhance gut barrier function.This study elucidated the potential mechanisms through which Lactobacillus mitigates lipopolysaccharide(LPS)-induced intestinal injury from the perspective of macrophage-intestinal epithelial cell interactions.Lactobacillus intervention improved the histopathological score;elevated ZO-1 and Occludin protein production;reduced CD16^(+)cell numbers;diminished IL-1β,IL-6,and TNF-αlevels;decreased inducible nitric oxide synthase(iNOS)expression;increased CD163^(+)cell numbers;elevated IL-10 concentration;and increased arginase-1(Arg1)expression in LPS-challenged piglets.Lactobacillus pretreatment also altered the colonic microbiota,thereby increasing the butyric acid concentration and GPR43 expression in the LPS-challenged piglets.Compared with those in the LPS group,sodium butyrate(SB)pretreatment decreased IL-1β,IL-6 and TNF-αsecretion and iNOS expression but increased IL-10 secretion and Arg1 expression in macrophages.The SB-pretreated macrophages reduced the protein expression of TLR4,MyD88,and phosphorylated NF-κB p65 but increased the protein expression of ZO-1 and Occludin in intestinal epithelial cells.Moreover,GLPG0974 blocked the beneficial effects of SB on macrophages and intestinal epithelial cells.This study demonstrated that Lactobacillus improves intestinal barrier function by regulating the macrophage phenotype through the control of butyric acid and GPR43 levels to further control inflammation.展开更多
Rheumatoid arthritis(RA)is a common chronic autoimmune disease characterized by joint pain,swelling and dysfunction[1].According to epidemiologic statistics,the incidence of RA is 1%–2%,and in severe cases,it can dev...Rheumatoid arthritis(RA)is a common chronic autoimmune disease characterized by joint pain,swelling and dysfunction[1].According to epidemiologic statistics,the incidence of RA is 1%–2%,and in severe cases,it can develop into joint deformity and disability,which brings a heavy burden to the family and society[2].However,the pathogenesis of RA is complex and involves multiple cellular interactions,which increases the difficulty of curing RA.Current therapeutic options,such as disease-modifying antirheumatic drugs,non-steroidal anti-inflammatory drugs,and biologics,still face the challenge of relapse after drug discontinuation[3,4].Therefore,the pathogenesis of RA needs to be analyzed in depth to break through the existing therapeutic bottlenecks and promote the iterative innovation of individualized diagnosis and treatment.展开更多
Background Inflammatory bowel disease is a significant health concern for both humans and large-scale farm animals.In the quest for effective alternatives to antibiotics,next-generation probiotics(NGPs)have emerged as...Background Inflammatory bowel disease is a significant health concern for both humans and large-scale farm animals.In the quest for effective alternatives to antibiotics,next-generation probiotics(NGPs)have emerged as a promising option.The genus Blautia presents a rich source of potential NGP strains.Here we successfully isolated Blautia hominis LYH1 strain from the intestines of healthy weaned piglets and characterized its biological traits.Its antiinflammatory activity was then assessed using macrophages,while its protective effects against colitis and gut barrier damage were validated in a DSS-induced mouse colitis model.Results B.hominis LYH1 displayed typical characteristics of an obligate anaerobe,including non-hemolytic and nonmotile features,and a genome enriched with carbohydrate-active enzyme genes.It produced metabolites with antibiotic-like compounds,demonstrating antimicrobial activity against Escherichia coli.In vitro,B.hominis LYH1 effectively inhibited pathogen replication in macrophages,reducing cellular infections and alleviating inflammatory damage.In vivo,oral administration of B.hominis LYH1 or its metabolites significantly mitigated DSS-induced colitis in mice by suppressing pro-inflammatory cytokines,inhibiting T-lymphocyte activation,and enhancing short-chain fatty acid production.Conclusions Our findings underscore B.hominis LYH1’s potential as a NGP for maintaining gut health and combating intestinal inflammation.These findings offer valuable insights into the development of antibiotic alternatives and innovative strategies for preventing and treating enteritis in both agricultural and medical settings.展开更多
Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polariz...Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polarization,to train the innate immune system by epigenic modification have been reported in laboratory animal research.Methods:In the current in vitro research,murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus,a coronavirus existed in mouse.At 3-,6-,12-,24-,and 48-h post infection(hpi.),the attached cells were washed with PBS and harvested in Trizol reagent.Then The harvest is subjected to transcriptome sequencing.Results:The transcriptome analysis showed the immediate(3 hpi.)up regulation of DEGs related to inflammation,like Il1b and Il6.DEGs related to M2 differential po-larization,like Irf4 showed up regulation at 24 hpi.,the late term after viral infection.In addition,DEGs related to metabolism and histone modification,like Ezh2 were de-tected,which might correlate with the trained immunity of macrophages.Conclusions:The current in vitro viral infection study showed the key innated im-munity character of macrophages,which suggested the replacement value of viral infection cells model,to reduce the animal usage in preclinical research.展开更多
BACKGROUND Deficient efferocytosis(i.e.,phagocytic clearance of apoptotic cells)by macrophages has been frequently reported in experimental models of type 2 diabetes(T2D).AIM To translate these findings to humans by t...BACKGROUND Deficient efferocytosis(i.e.,phagocytic clearance of apoptotic cells)by macrophages has been frequently reported in experimental models of type 2 diabetes(T2D).AIM To translate these findings to humans by testing whether the efferocytosis capacity of blood monocytes and monocyte-derived macrophages is impaired in T2D patients.METHODS Overall,30 patients with poorly controlled T2D[glycosylated hemoglobin(HbA1c)≥8.0%]and 30 age-and sex-matched control subjects were enrolled in the study.The efferocytosis capacities of peripheral blood monocytes and monocyte-derived macrophages were assessed by flow cytometry and immunostaining.Macrophage membrane CD14 expression was examined by flow cytometry.Metabolic factors such as 25(OH)D and immune factors such as interleukin-1βwere also measured.RESULTS The mean monocyte efferocytosis index in the diabetes group was significantly lower than that in the control group.Notably,efferocytosis remained impaired after monocytes differentiated into macrophages.Additionally,the percentages of classical monocytes(CD14^(++)CD16-monocytes)and CD14^(+)macrophages were significantly lower in the diabetes group.Multivariate linear regression analysis in diabetes patients demonstrated that the monocyte efferocytosis index was independently associated with the HbA1c level,and that the macrophage efferocytosis index was significantly associated with the percentage of CD14^(+)macrophages.CONCLUSION Impaired efferocytosis was observed in T2D patients,with poor glycemic control affecting both blood monocytes and monocyte-derived macrophages.The efferocytosis index was negatively associated with metrics of glycemic control,and glucotoxicity may impact efferocytosis through reducing CD14 expression on both monocytes and macrophages.展开更多
Complement C3 plays a critical role in periodontitis.However,its source,role and underlying mechanisms remain unclear.In our study,by analyzing single-cell sequencing data from mouse model of periodontitis,we identifi...Complement C3 plays a critical role in periodontitis.However,its source,role and underlying mechanisms remain unclear.In our study,by analyzing single-cell sequencing data from mouse model of periodontitis,we identified that C3 is primarily derived from periodontal fibroblasts.Subsequently,we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis.C3ar−/−mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice,characterized by mild gingival tissue damage and reduced alveolar bone loss.This reduction was associated with decreased production of proinflammatory mediators and reduced osteoclast infiltration in the periodontal tissues.Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation.Finally,by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis,we found that the results observed in mice were consistent with human data.Therefore,our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis,driven by macrophage M1 polarization and osteoclast differentiation.These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.展开更多
The role and regulatory mechanisms of macrophage polarization in cardiac transplantation have gained significant attention.Macrophages can polarize into either the M1(pro-inflammatory)or M2(anti-inflammatory)phenotype...The role and regulatory mechanisms of macrophage polarization in cardiac transplantation have gained significant attention.Macrophages can polarize into either the M1(pro-inflammatory)or M2(anti-inflammatory)phenotype in response to environmental cues.M1 macrophages facilitate transplant rejection by releasing inflammatory mediators and activating T cells,whereas M2 macrophages support graft survival by secreting antiinflammatory factors and promoting tissue repair.Mitochondrial quality control regulation plays a crucial role in macrophage polarization,which may influence graft survival and immune responses.This review provides an overview of the current understanding of mitochondrial quality control-regulated macrophage polarization in cardiac transplantation,its effects on graft outcomes,and potential therapeutic strategies to modulate this process to enhance transplant success rates.The review was conducted by systematically analyzing recent studies and integrating findings from key research articles to synthesize a comprehensive understanding of this emerging field.展开更多
基金supported by Ministry of Science and Technology China Brain Initiative Grant,No.2022ZD0204702(to ZY)the National Natural Science Foundation of China,No.82371357(to LC)+2 种基金Foundation for Military Medicine,No.16QNP085(to ZY)Navy Medical University Basic Medical College“Yi Zhang”Basic Medical Talent Development and Support Program,Nos.JCYZRC-D-022(to TC)and JCYZRC-D-024(to HD)Science and Technology Innovation Special Fund of Shanghai Baoshan District,No.2023-E-05(to YW).
文摘Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.
基金The National Natural Science Foundation of China(no.82204006)the Science and Technology of Project of Hebei Education Department(QN2022009)+1 种基金the Provincial Graduate Student Innovation Funding Project of Hebei Province(CXZZBS2022104)the National Natural Science Foundation of Hebei Province(H2020209292).
文摘Background:The aim was to explore the effect of macrophage polarization and macrophage-to-myofibroblast transition(MMT)in silicosis.Methods:Male Wistar rats were divided into a control group and a silicosis group developed using a HOPE MED 8050 dynamic automatic dusting system.Murine mac-rophage MH-S cells were randomly divided into a control group and an SiO_(2) group.The pathological changes in lung tissue were observed using hematoxylin and eosin(HE)and Van Gieson(VG)staining.The distribution and location of macrophage marker(F4/80),M1 macrophage marker(iNOS),M2 macrophage marker(CD206),and myofibroblast marker(α-smooth muscle actin[α-SMA])were detected using immu-nohistochemical and immunofluorescent staining.The expression changes in iNOS,Arg,α-SMA,vimentin,and type I collagen(Col I)were measured using Western blot.Results:The results of HE and VG staining showed obvious silicon nodule formation and the distribution of thick collagen fibers in the lung tissue of the silicosis group.Macrophage marker F4/80 increased gradually from 8 to 32 weeks after exposure to silica.Immunohistochemical and immunofluorescent staining results revealed that there were more iNOS-positive cells and some CD206-positive cells in the lung tissue of the silicosis group at 8 weeks.More CD206-positive cells were found in the silicon nodules of the lung tissues in the silicosis group at 32 weeks.Western blot analysis showed that the expressions of Inducible nitric oxide synthase and Arg protein in the lung tissues of the silicosis group were upregulated compared with those of the con-trol group.The results of immunofluorescence staining showed the co-expression of F4/80,α-SMA,and Col I,and CD206 andα-SMA were co-expressed in the lung tissue of the silicosis group.The extracted rat alveolar lavage fluid revealed F4/80+α-SMA+,CD206+α-SMA+,and F4/80+α-SMA+Col I+cells using immunofluorescence staining.Similar results were also found in MH-S cells induced by SiO_(2).Conclusions:The development of silicosis is accompanied by macrophage polarization and MMT.
文摘BACKGROUND Macrophages play a crucial role in the tumor microenvironment,displaying remarkable plasticity that allows them to either suppress or promote tumor progression.Their polarization into M1 or M2 phenotypes could have significant prognostic implications,and manipulating this polarization may offer a novel approach to controlling colorectal neoplasms.AIM To evaluate the infiltration rates of M1 and M2 macrophages in colorectal neoplasia,specifically comparing cases with and without metalloproteinase mutations.Additionally,it sought to explore potential prognostic factors as-sociated with the disease.
基金Natural Science Foundation of Anhui Province,No.2208085MH216Major Natural Science and Technology Project of Bengbu Medical College,No.2020byfy004Scientific Research Program of Anhui Provincial Health Commission,No.AHWJ2023BAc10028.
文摘BACKGROUND Macrophages are central to the orchestration of immune responses,inflammatory processes,and the pathogenesis of diabetic complications.The dynamic polarization of macrophages into M1 and M2 phenotypes critically modulates inflammation and contributes to the progression of diabetic nephropathy.Sodiumglucose cotransporter 2 inhibitors such as dapagliflozin,which are acclaimed for their efficacy in diabetes management,may influence macrophage polarization,thereby ameliorating diabetic nephropathy.This investigation delves into these mechanistic pathways,aiming to elucidate novel therapeutic strategies for diabetes.AIM To investigate the inhibitory effect of dapagliflozin on macrophage M1 polarization and apoptosis and to explore its mechanism of action.METHODS We established a murine model of type 2 diabetes mellitus and harvested peritoneal macrophages following treatment with dapagliflozin.Concurrently,the human monocyte cell line cells were used for in vitro studies.Macrophage viability was assessed in a cell counting kit 8 assay,whereas apoptosis was evaluated by Annexin V/propidium iodide staining.Protein expression was examined through western blotting,and the expression levels of macrophage M1 surface immunosorbent assay,and quantitative real-time polymerase chain reaction analyses.RESULTS Dapagliflozin attenuated M1 macrophage polarization and mitigated apoptosis in the abdominal macrophages of diabetic mice,evidenced by the downregulation of proapoptotic genes(Caspase 3),inflammatory cytokines[interleukin(IL)-6,tumor necrosis factor-α,and IL-1β],and M1 surface markers(inducible nitric oxide synthase,and cluster of differentiation 86),as well as the upregulation of the antiapoptotic gene BCL2.Moreover,dapagliflozin suppressed the expression of proteins associated with the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway(PI3K,AKT,phosphorylated protein kinase B).These observations were corroborated in vitro,where we found that the modulatory effects of dapagliflozin were abrogated by 740Y-P,an activator of the PI3K/AKT signaling pathway.CONCLUSION Dapagliflozin attenuates the polarization of macrophages toward the M1 phenotype,thereby mitigating inflammation and promoting macrophage apoptosis.These effects are likely mediated through the inhibition of the PI3K/AKT signaling pathway.
文摘Liver cancer,and in particular hepatocellular carcinoma(HCC)is a disease of rising prevalence and incidence.To date,definitive treatment options include either surgical excision or ablation of the affected area.With increasing research on several pathways that could be involved in the progression of HCC,new elements within these pathways emerge as potential targets for novel therapies.The WNT/β-catenin pathway favors the presence of M2 tumor-associated macrophages which in turn promote tumor growth and metastasis.The inhibition of this pathway is considered a good candidate for such targeted therapeutic interventions.Interestingly,as Huang et al show in their recently published article,Calculus bovis which is used in traditional Chinese medicine can exert an inhibitory effect on theβ-catenin pathway and become a potential candidate for targeted pharmacotherapy against liver cancer.
基金National Natural Science Foundation of China,No.81873934and Jinan Science and Technology Planning Project,No.202225065.
文摘BACKGROUND Mesenchymal stem cells,found in various tissues,possess significant healing and immunomodulatory properties,influencing macrophage polarization,which is essential for wound repair.However,chronic wounds present significant therapeutic challenges,requiring novel strategies to improve healing outcomes.AIM To investigate the potential of fetal dermal mesenchymal stem cells(FDMSCs)in enhancing wound healing through modulation of macrophage polarization,specifically by promoting the M2 phenotype to address inflammatory responses in chronic wounds.METHODS FDMSCs were isolated from BalB/C mice and co-cultured with RAW264.7 macrophages to assess their effects on macrophage polarization.Flow cytometry,quantitative reverse transcriptase polymerase chain reaction,and histological analyses were employed to evaluate shifts in macrophage phenotype and wound healing in a mouse model.Statistical analysis was performed using GraphPad Prism.RESULTS FDMSCs induced macrophage polarization from the M1 to M2 phenotype,as demonstrated by a reduction in proinflammatory markers(inducible nitric oxide synthase,interleukin-6)and an increase in anti-inflammatory markers[mannose receptor(CD206),arginase-1]in co-cultured RAW264.7 macrophages.These shifts were confirmed by flow cytometry.In an acute skin wound model,FDMSC-treated mice exhibited faster wound healing,enhanced collagen deposition,and improved vascular regeneration compared to controls.Significantly higher expression of arginase-1 further indicated an enriched M2 macrophage environment.CONCLUSION FDMSCs effectively modulate macrophage polarization from M1 to M2,reduce inflammation,and enhance tissue repair,demonstrating their potential as an immunomodulatory strategy in wound healing.These findings highlight the promising therapeutic application of FDMSCs in managing chronic wounds.
文摘Background : To study the relationships among emodin, synovial fibroblasts (FLSs), and macrophages (STMs) to provide guidance for the use of emodin in rheumatoid arthritis (RA) treatment. Methods : RA clinical samples from patients with different pathological processes were collected, and the correlations between the subsets of FLSs and STMs and pathological processes were analyzed via flow cytometry. In vitro experimental methods such as enzyme linked immunosorbent assay (ELISA), Western blotting, Transwell assays, CCK- 8 assays and cell coculture were used to assess cell proliferation, migration and secretion of inflammatory factors. A collagen- induced arthritis mouse model was constructed to investigate the therapeutic potential of emodin in RA by flow cytometry, micro- CT and staining. Results : Unique subsets of FLSs and STMs, namely, FAPα ^(+)THY1 − FLSs, FAPα ^(+)THY1 ^(+)FLSs, and MerTK ^(pos) TREM2 ^(high) STMs, were identified in synovial tissues from RA patients. The number of MerTK ^(pos) TREM2 ^(high) STMs was negatively correlated with the degree of damage in RA, while the number of FAPα ^(+)THY1 − FLSs was positively correlated with damage. On the one hand, emodin promoted the aggregation of MerTKposTREM2high STMs. Moreover, MerTK pos TREM2 high STM- mediated secretion of exosomes was promoted, which can inhibit the secretion of pro- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs and promote the secretion of anti- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs, thereby inhibiting FAPα ^(+)THY1 − FLS proliferation and migration, improving the local immune microenvironment, and inhibiting RA damage. Conclusion : Emodin was shown to regulate the aggregation of STM subsets and exosome secretion, affecting the secretion, proliferation and migration of inflammatory factors in FLS subsets, and ultimately achieving good therapeutic efficacy in RA patients, suggesting that it has important clinical value.
基金supported by the National Natural Science Foundation of China(82071143,82371000,82270361)Key Research and Development Program of Jiangsu Province(BE2022795)+2 种基金the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_1801)the Jiangsu Province Capability Improvement Project through the Science,Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit(YJXYYJSDW4)Jiangsu Provincial Medical Innovation Center(CXZX202227).
文摘Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon(RAP).Despite its therapeutic effects,the surgical risk and unclear mechanism hamper the clinical application.Numerous evidences support macrophages as the key immune cells during bone remodeling.Our study discovered that the monocyte-derived macrophages primarily exhibited a pro-inflammatory phenotype that dominated bone remodeling in corticotomy by CX3CR1CreERT2;R26GFP lineage tracing system.Fluorescence staining,flow cytometry analysis,and western blot determined the significantly enhanced expression of binding immunoglobulin protein(BiP)and emphasized the activation of sensor activating transcription factor 6(ATF6)in macrophages.Then,we verified that macrophage specific ATF6 deletion(ATF6f/f;CX3CR1CreERT2 mice)decreased the proportion of pro-inflammatory macrophages and therefore blocked the acceleration effect of corticotomy.In contrast,macrophage ATF6 overexpression exaggerated the acceleration of orthodontic tooth movement.In vitro experiments also proved that higher proportion of pro-inflammatory macrophages was positively correlated with higher expression of ATF6.At the mechanism level,RNA-seq and CUT&Tag analysis demonstrated that ATF6 modulated the macrophage-orchestrated inflammation through interacting with Tnfαpromotor and augmenting its transcription.Additionally,molecular docking simulation and dual-luciferase reporter system indicated the possible binding sites outside of the traditional endoplasmic reticulum-stress response element(ERSE).Taken together,ATF6 may aggravate orthodontic bone remodeling by promoting Tnfαtranscription in macrophages,suggesting that ATF6 may represent a promising therapeutic target for non-invasive accelerated orthodontics.
基金Supported by the National Natural Science Foundation of China,No.81973684Natural Science Foundation of Sichuan Province,No.2023NSFSC1760Youth Talent Fund of Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital,No.2021QN09。
文摘BACKGROUND Periodontitis,when exacerbated by diabetes,is characterized by increased M1 macrophage polarization and decreased M2 polarization.O-linkedβ-N-acetylglucosamine(O-GlcNAcylation),catalyzed by O-GlcNAc transferase(OGT),promotes inflammatory responses in diabetic periodontitis(DP).Additionally,p38 mitogen-activated protein kinase regulates macrophage polarization.However,the interplay between OGT,macrophage polarization,and p38 signaling in the progression of DP remains unexplored.AIM To investigate the effect of OGT on macrophage polarization in DP and its role in mediating O-GlcNAcylation of p38.METHODS For in vivo experiments,mice were divided into four groups:Control,DP model,model+short hairpin(sh)RNAnegative control,and model+sh-OGT.Diabetes was induced by streptozotocin,followed by ligation and lipopolysaccharide(LPS)administration to induce periodontitis.The impact of OGT was assessed by injecting sh-OGT lentivirus.Maxillary bone destruction was evaluated using micro-computed tomography analysis and tartrateresistant acid phosphatase staining,while macrophage polarization was determined through quantitative real-time polymerase chain reaction(qPCR)and immunohistochemistry.For in vitro experiments,RAW264.7 cells were treated with LPS and high glucose(HG)(25 mmol/L D-glucose)to establish a cell model of DP.OGT was inhibited by OGT inhibitor(OSMI4)treatment and knocked down by sh-OGT transfection.M1/M2 polarization was analyzed using qPCR,immunofluorescence,and flow cytometry.Levels of O-GlcNAcylation were measured using immunoprecipitation and western blotting.RESULTS Our results demonstrated that M1 macrophage polarization led to maxillary bone loss in DP mice,associated with elevated O-GlcNAcylation and OGT levels.Knockdown of OGT promoted the shift from M1 to M2 macrophage polarization in both mouse periodontal tissues and LPS+HG-induced RAW264.7 cells.Furthermore,LPS+HG enhanced the O-GlcNAcylation of p38 in RAW264.7 cells.OGT interacted with p38 to promote its O-GlcNAcylation at residues A28,T241,and T347,as well as its phosphorylation at residue Y221.CONCLUSION Inhibition of OGT-mediated p38 O-GlcNAcylation deactivates the p38 pathway by suppressing its self-phosphorylation,thereby promoting M1 to M2 macrophage polarization and mitigating DP.These findings suggested that modulating macrophage polarization through regulation of O-GlcNAcylation may represent a novel therapeutic strategy for treating DP.
基金supported by the National Natural Science Foundation of China(No.82302772)Guizhou Basic Research Project(No.ZK[2023]General 201)partially supported by Wuhan Kangchuang Biotechnology Co.,Ltd。
文摘Macrophages undergo dynamic transitions between M1 and M2 states,exerting profound influences on both inflammatory and regenerative processes.The biocompatible and wound-healing properties of decellularized amniotic membrane(d AM)make it a subject of exploration for its potential impact on the anti-inflammatory response of macrophages.Experimental findings unequivocally demonstrate that d AM promotes anti-inflammatory M2 polarization of macrophage,with its cytokine-rich content posited as a potential mediator.The application of RNA sequencing unveils differential gene expression,implicating the hypoxia inducible factor-1α(HIF-1α)signaling pathway in this intricate interplay.Subsequent investigation further demonstrates that d AM facilitates anti-inflammatory M2 polarization of macrophage through the upregulation of epidermal growth factor(EGF),which,in turn,activates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway and stabilizes HIF-1α.This cascade results in a noteworthy augmentation of anti-inflammatory gene expression.This study significantly contributes to advancing our comprehension of d AM's immunomodulatory role in tissue repair,thereby suggesting promising therapeutic potential.
基金supported by the National Key Research and Development Program of China(No.2019YFC1712100)the National Natural Science Foundation of China(No.82105017)。
文摘Objective:The occurrence and development of atrial fibrillation(AF)are influenced by the autonomic nervous system and inflammation.Acupuncture is an effective treatment for AF.This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms.Methods:Male Sprague-Dawley rats(n=130)were randomly divided into blank control(Con),sham operation(Sham),AF,and acupuncture treatment(Acu)groups.A paroxysmal AF model was established by rapid atrial pacing through the jugular vein.Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint(PC6)for 20 min daily for seven days.The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture.The AF induction rate,AF duration,cardiac electrophysiological parameters,and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals.After the intervention,the rats were euthanized,and atrial morphology was assessed using haematoxylin and eosin staining.The expression of macrophage F4/80 antigen(F4/80)and cluster of differentiation(CD)86 in atrial myocardial tissue was detected using immunohistochemistry,immunofluorescence and flow cytometry.The expression levels or contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-a(TNF-a),a7 nicotinic acetylcholine receptor(a7nAChR),phosphorylated Janus kinase 2(p-JAK2),and phosphorylated signal transducer and activator of transcription 3(p-STAT3)in atrial myocardial tissue were detected using Western blotting,reverse transcription-quantitative polymerase chain reaction,or enzyme-linked immunosorbent assay.The role of a7nAChR in acupuncture treatment was verified by intraperitoneal injection of the a7nAChR antagonist methyllycaconitine(MLA).Results:Compared with the AF group,acupuncture significantly reduced AF duration and induction rate,improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance.It also decreased the pro-inflammatory M1 macrophage proportion,alleviating myocardial injury and infiltration.MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect.Results suggest that acupuncture triggers the a7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation.Conclusion:Acupuncture significantly reduced the AF induction rate,shortened AF duration,improved cardiac electrophysiological parameters,enhanced vagus nerve activity,and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF.
基金Supported by the Qilu Medical School Traditional Chinese Medicine Academic School Inheritance Project,No.93 LW[2022]Construction Project of the Inheritance Studio of National Famous Traditional Chinese Medicine Experts,Traditional Chinese Medicine Teaching Letter No.75[2022]Qilu Health and Fitness Talents in 2019,No.3 LWRZ[2020].
文摘BACKGROUND Diabetic foot ulcers(DFUs)are a significant contributor to disability and mortality in diabetic patients.Macrophage polarization and functional regulation are promising areas of research and show therapeutic potential in the field of DFU healing.However,the complex mechanism,the difficulty in clinical translation,and the large heterogeneity present significant challenges.Hence,this study was to comprehensively analyze the publication status and trends of studies on macrophage polarization and DFU healing.AIM To examine the relevant literature on macrophage polarization in DFU healing.METHODS A bibliometric analysis was conducted using the Web of Science database.Relevant literature was retrieved from the Web of Science Core Collection database between 2013 to 2023 using literature visualization and analysis software(VOSviewer and CiteSpace)and bibliometric online platforms.The obtained literature was then subjected to visualization and analysis of different countries/regions,institutions,journals,authors,and keywords to reveal the research’s major trends and focus.RESULTS The number of publications on the role of macrophage polarization in DFU healing increased rapidly from 2013 to 2023,especially in the latter period.Chinese researchers were the most prolific in this field,with 217 publications,while American researchers had been engaged in this field for a longer period.Qian Tan of Nanjing Drum Tower Hospital and Qian Ding of Nanjing University were the first to publish in this field.Shanghai Jiao Tong University was the institution with the most publications(27).The keywords“bone marrow”,“adjustment,replacement,response,tissue repair”,and“activation,repair,differentiation”appeared more frequently.The study of macrophage polarization in DFU healing focused on the regulatory mechanism,gene expression,and other aspects.CONCLUSION This study through the bibliometric method reveals the research trends and development trends in this field of macrophage polarization in DFU healing from 2013 to 2023 in the Web of Science Core Collection database.The key hotspots in this field mainly include the regulation of macrophage activation,gene expression,wound tissue repair,and new wound materials.This study provides references for future research directions.
基金supported by National Natural Science Foundation of China(82204766,82074122,82174078)Natural Science Foundation of Hunan province(2023JJ40490)+9 种基金Changjiang Scholars Program in Ministry Education,People’s Republic of China(T2019133)Xiaohe Sci-Tech Talents Special Funding under Hunan Provincial Sci-Tech Talents Sponsorship Program(2023TJ-X71)Science and Technology Innovation Program of Hunan Province(2024RC3201)Scientific research project of Hunan Provincial Education Department(21B0394,21A0239)Research Project of Hunan Administration of Traditional Chinese Medicine(B2023055)Changsha Outstanding Innovative Youth Training Program(kq2306021)Outstanding Youth Program of Hunan University of Chinese Medicine(202202)Postgraduate Innovation Project of Hunan University of Chinese Medicine(2024CX090)Open Foundation Project of Hunan International Joint Laboratory of Traditional Chinese Medicine(2022GJSYS02)Undergraduate Research and Innovation Foundation of Hunan University of Chinese Medicine(2023BKS097).
文摘Abnormal activation of macrophages and osteoclasts(OCs)contributes significantly to rheumatoid arthritis(RA)development by secretion of numerous inflammatory factors.Notably,these cells exhibit significant upregulation of folate receptor proteins on their surfaces.Unfortunately,there is a current lack of safe and effective therapeutic drugs for RA.Xuetongsu(XTS),a triterpenoid compound extracted fromKadsura heteroclita Roxb Craib,has demonstrated the ability to significantly inhibit the proliferation of RA fibroblast-like synoviocytes(RAFLS).However,its clinical application is hampered by poor targeting and short half-life.To address these drawbacks,we previously developed a nano-drug system named HRPS nanoparticles(NPs),which effectively targets RAFLS and inhibits synovial hyperplasia.However,this system overlooked the essential role of OCs in RA-related bone destruction.Therefore,we designed a novel folate-modified biomimetic Prussian blue(PB)-XTS NP(FMPX NP)for the selective delivery of XTS into inflammatory macrophages and OCs.The NP exhibits an excellent photothermal effect when assisted by laser irradiation,facilitating targeted release of XTS within inflammatory macrophages and OCs.The synergistic anti-inflammatory and reactive oxygen species scavenging effects of PB NPs and XTS are mediated by the inhibition of the NF-κB signaling pathway in inflammatory macrophages and RANK/RANKL/NFATc1 signaling pathway in OCs.In vivo experiments showed that FMPX NPs extended the half-life of XTS by 2.32 times,decreased hind foot swelling from 12.10±0.49 mm to 8.24±0.09 mm in the model group,and prevented bone damage.In conclusion,this study introduces a novel dual-targeted nano-based therapy for RA joints and highlights its potential for biochemical photothermal triple therapy for RA.FMPX NPs inhibit arthritis-related inflammation and bone destruction through a dual-target strategy,providing new insights for targeted drug therapies in clinical RA treatment.
基金supported by the National Nature Science Foundation of China(32272898)the National Key Research and Development Program(2021YFA0805904)the Fundamental Research Funds for the Central Universities(2662020DKQD004).
文摘Lactobacillus species have excellent abilities to reduce intestinal inflammation and enhance gut barrier function.This study elucidated the potential mechanisms through which Lactobacillus mitigates lipopolysaccharide(LPS)-induced intestinal injury from the perspective of macrophage-intestinal epithelial cell interactions.Lactobacillus intervention improved the histopathological score;elevated ZO-1 and Occludin protein production;reduced CD16^(+)cell numbers;diminished IL-1β,IL-6,and TNF-αlevels;decreased inducible nitric oxide synthase(iNOS)expression;increased CD163^(+)cell numbers;elevated IL-10 concentration;and increased arginase-1(Arg1)expression in LPS-challenged piglets.Lactobacillus pretreatment also altered the colonic microbiota,thereby increasing the butyric acid concentration and GPR43 expression in the LPS-challenged piglets.Compared with those in the LPS group,sodium butyrate(SB)pretreatment decreased IL-1β,IL-6 and TNF-αsecretion and iNOS expression but increased IL-10 secretion and Arg1 expression in macrophages.The SB-pretreated macrophages reduced the protein expression of TLR4,MyD88,and phosphorylated NF-κB p65 but increased the protein expression of ZO-1 and Occludin in intestinal epithelial cells.Moreover,GLPG0974 blocked the beneficial effects of SB on macrophages and intestinal epithelial cells.This study demonstrated that Lactobacillus improves intestinal barrier function by regulating the macrophage phenotype through the control of butyric acid and GPR43 levels to further control inflammation.
文摘Rheumatoid arthritis(RA)is a common chronic autoimmune disease characterized by joint pain,swelling and dysfunction[1].According to epidemiologic statistics,the incidence of RA is 1%–2%,and in severe cases,it can develop into joint deformity and disability,which brings a heavy burden to the family and society[2].However,the pathogenesis of RA is complex and involves multiple cellular interactions,which increases the difficulty of curing RA.Current therapeutic options,such as disease-modifying antirheumatic drugs,non-steroidal anti-inflammatory drugs,and biologics,still face the challenge of relapse after drug discontinuation[3,4].Therefore,the pathogenesis of RA needs to be analyzed in depth to break through the existing therapeutic bottlenecks and promote the iterative innovation of individualized diagnosis and treatment.
基金supported by Natural Science Foundation of Sichuan Province(2023NSFSC0237)National Natural Science Foundation of China(32372900)Major Special Projects in Sichuan Province(2021ZDZX0009).
文摘Background Inflammatory bowel disease is a significant health concern for both humans and large-scale farm animals.In the quest for effective alternatives to antibiotics,next-generation probiotics(NGPs)have emerged as a promising option.The genus Blautia presents a rich source of potential NGP strains.Here we successfully isolated Blautia hominis LYH1 strain from the intestines of healthy weaned piglets and characterized its biological traits.Its antiinflammatory activity was then assessed using macrophages,while its protective effects against colitis and gut barrier damage were validated in a DSS-induced mouse colitis model.Results B.hominis LYH1 displayed typical characteristics of an obligate anaerobe,including non-hemolytic and nonmotile features,and a genome enriched with carbohydrate-active enzyme genes.It produced metabolites with antibiotic-like compounds,demonstrating antimicrobial activity against Escherichia coli.In vitro,B.hominis LYH1 effectively inhibited pathogen replication in macrophages,reducing cellular infections and alleviating inflammatory damage.In vivo,oral administration of B.hominis LYH1 or its metabolites significantly mitigated DSS-induced colitis in mice by suppressing pro-inflammatory cytokines,inhibiting T-lymphocyte activation,and enhancing short-chain fatty acid production.Conclusions Our findings underscore B.hominis LYH1’s potential as a NGP for maintaining gut health and combating intestinal inflammation.These findings offer valuable insights into the development of antibiotic alternatives and innovative strategies for preventing and treating enteritis in both agricultural and medical settings.
基金CAMs innovation Fund for Medical Sciences,Grant/Award Number:2022-12M-CoV19-005National Key Projects,Grant/Award Number:2023YFF0724900 and 2021YFF0702802。
文摘Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polarization,to train the innate immune system by epigenic modification have been reported in laboratory animal research.Methods:In the current in vitro research,murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus,a coronavirus existed in mouse.At 3-,6-,12-,24-,and 48-h post infection(hpi.),the attached cells were washed with PBS and harvested in Trizol reagent.Then The harvest is subjected to transcriptome sequencing.Results:The transcriptome analysis showed the immediate(3 hpi.)up regulation of DEGs related to inflammation,like Il1b and Il6.DEGs related to M2 differential po-larization,like Irf4 showed up regulation at 24 hpi.,the late term after viral infection.In addition,DEGs related to metabolism and histone modification,like Ezh2 were de-tected,which might correlate with the trained immunity of macrophages.Conclusions:The current in vitro viral infection study showed the key innated im-munity character of macrophages,which suggested the replacement value of viral infection cells model,to reduce the animal usage in preclinical research.
基金Supported by National Natural Science Foundation of China,No.81970669,No.82170835,and No.82100848Shanghai Municipal Health Commission,No.202240107,and No.20234Y0040China Endocrine Metabolism Research Program of Excellence,No.2023-N-03-05。
文摘BACKGROUND Deficient efferocytosis(i.e.,phagocytic clearance of apoptotic cells)by macrophages has been frequently reported in experimental models of type 2 diabetes(T2D).AIM To translate these findings to humans by testing whether the efferocytosis capacity of blood monocytes and monocyte-derived macrophages is impaired in T2D patients.METHODS Overall,30 patients with poorly controlled T2D[glycosylated hemoglobin(HbA1c)≥8.0%]and 30 age-and sex-matched control subjects were enrolled in the study.The efferocytosis capacities of peripheral blood monocytes and monocyte-derived macrophages were assessed by flow cytometry and immunostaining.Macrophage membrane CD14 expression was examined by flow cytometry.Metabolic factors such as 25(OH)D and immune factors such as interleukin-1βwere also measured.RESULTS The mean monocyte efferocytosis index in the diabetes group was significantly lower than that in the control group.Notably,efferocytosis remained impaired after monocytes differentiated into macrophages.Additionally,the percentages of classical monocytes(CD14^(++)CD16-monocytes)and CD14^(+)macrophages were significantly lower in the diabetes group.Multivariate linear regression analysis in diabetes patients demonstrated that the monocyte efferocytosis index was independently associated with the HbA1c level,and that the macrophage efferocytosis index was significantly associated with the percentage of CD14^(+)macrophages.CONCLUSION Impaired efferocytosis was observed in T2D patients,with poor glycemic control affecting both blood monocytes and monocyte-derived macrophages.The efferocytosis index was negatively associated with metrics of glycemic control,and glucotoxicity may impact efferocytosis through reducing CD14 expression on both monocytes and macrophages.
基金supported by the National Key R&D Program of China(No.2022YFC2504200)the National Natural Science Foundation of China(Nos.82370936,81920108012,82471032).
文摘Complement C3 plays a critical role in periodontitis.However,its source,role and underlying mechanisms remain unclear.In our study,by analyzing single-cell sequencing data from mouse model of periodontitis,we identified that C3 is primarily derived from periodontal fibroblasts.Subsequently,we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis.C3ar−/−mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice,characterized by mild gingival tissue damage and reduced alveolar bone loss.This reduction was associated with decreased production of proinflammatory mediators and reduced osteoclast infiltration in the periodontal tissues.Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation.Finally,by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis,we found that the results observed in mice were consistent with human data.Therefore,our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis,driven by macrophage M1 polarization and osteoclast differentiation.These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.
基金supported by Guangxi Natural Science Foundation(2023GXNSFAA026128).
文摘The role and regulatory mechanisms of macrophage polarization in cardiac transplantation have gained significant attention.Macrophages can polarize into either the M1(pro-inflammatory)or M2(anti-inflammatory)phenotype in response to environmental cues.M1 macrophages facilitate transplant rejection by releasing inflammatory mediators and activating T cells,whereas M2 macrophages support graft survival by secreting antiinflammatory factors and promoting tissue repair.Mitochondrial quality control regulation plays a crucial role in macrophage polarization,which may influence graft survival and immune responses.This review provides an overview of the current understanding of mitochondrial quality control-regulated macrophage polarization in cardiac transplantation,its effects on graft outcomes,and potential therapeutic strategies to modulate this process to enhance transplant success rates.The review was conducted by systematically analyzing recent studies and integrating findings from key research articles to synthesize a comprehensive understanding of this emerging field.
