Macrophage Activation Syndrome as the Primary Presentation of Pediatric Systemic Lupus Erythematosus: A Case Report and Review of the Literature

Macrophage activation syndrome (MAS), in its secondary form, often complicates rheumatic diseases but rarely constitutes a mode of revelation. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology that primarily affects women in adulthood. MAS is a serious condition that may be the first presentation of SLE. Here, we report the case of a 4-year-old female with MAS as the primary manifestation of Systemic Lupus Erythematosus (SLE). In this case, we outline the characteristics of a complex case of SLE that was initially accompanied with MAS, and also review the literature to discuss the clinical, biological, and therapeutic aspects of this condition.

Infiltration by monocytes of the central nervous system and its role in multiple sclerosis: reflections on therapeutic strategies

Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.

Role of macrophage polarization in diabetic foot ulcer healing:A bibliometric study

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.

WNT/β-catenin-M2 macrophage interplay as a target for therapy against hepatocellular carcinoma:Role of Calculus bovis

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.

Dapagliflozin exerts anti-apoptotic effects by mitigating macrophage polarization via modulation of the phosphoinositide 3-kinase/protein kinase B signaling pathway

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.

The transcriptome of MHV-infected RAW264.7 cells offers an alternative model for macrophage innate immunity research

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.

Macrophage polarization in cardiac transplantation:Insights into immune modulation and therapeutic approaches

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.

O-linked β-N-acetylglucosamine transferase regulates macrophage polarization in diabetic periodontitis: In vivo and in vitro study

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.

Emodin promotes the recovery of rheumatoid arthritis by regulating the crosstalk between macrophage subsets and synovial fibroblast subsets

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 path- ological processes were analyzed via flow cytometry. In vitro experimental methods such as enzyme linked immunosorbent assay (ELISA), Western blotting, Transwell as- says, 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 cytom- etry, 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 secre- tion 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 exo- some secretion, affecting the secretion, proliferation and migration of inflammatory factors in FLS subsets, and ultimately achieving good therapeutic efficacy in RA pa- tients, suggesting that it has important clinical value.

Regulation of macrophage activation in the liver after acute injury: Role of the fibrinolytic system

The liver functions,in part,to prevent exposure of the body to potentially harmful substances ingested in the diet.While it is highly efficient at accomplishing this,it is frequently prone to liver injury due to the biotransformation of xenobiotics into toxic metabolites.To counter this injury,the liver has evolved a unique capacity to rapidly and efficiently repair itself.Successful resolution of acute liver injury relies on hepatic macrophage populations that orchestrate the reparative response.After injury,Kupffer cells,the resident macrophages of the liver,become activated and secrete proinflammatory cytokines.These cytokines recruit other immune cells,including monocyte-derived macrophages,to the liver where they contribute to the repair process.Monocyte-derived macrophages traffic into the necrotic foci where they rapidly phagocytose dead cell debris.Simultaneous with this process,these cells change phenotype from a proinflammatory macrophage to a prorestorative macrophage that produce pro-mitogenic growth factors and antiinflammatory cytokines.Ultimately this process triggers resolution of inflammation,and along with proliferation of other hepatic cells,restores the liver architecture and function.While the mechanisms regulating specific macrophage functions during repair remain to be elucidated,recent studies indicate a key role for the fibrinolytic system in coordinating macrophage function during repair.In this review,we will highlight the function and role of hepatic macrophages in repair after acute liver injury,and will discuss the role of the fibrinolytic enzyme,plasmin,in regulation of these various processes.

Respiratory failure and macrophage activation syndrome as an onset of systemic lupus erythematosus: A case report

BACKGROUND Macrophage activation syndrome(MAS)is defined as a specific secondary hemophagocytic lymphohistiocytosis that refers particularly to those triggered by autoimmune diseases.MAS is a rare and highly lethal complication of systemic lupus erythematosus(SLE),which can be associated with,or mimic,disease flare.However,the data regarding the clinical course,management and outcome of SLE with MAS is limited,especially in adults.Lack of clinical recognition of the disease often leads to poor prognosis.CASE SUMMARY We report a 36-year-old Chinese woman without relevant past medical history who was admitted to hospital with a 6-d history of jaundice and a high fever of 39.4°C lasting one day.Abdominal magnetic resonance imaging excluded obstructive jaundice,no infection was identified and empiric superior antibiotic treatment(meropenem)showed no clinical improvement.However,newly emerged pancytopenia and respiratory failure endangered the patient’s life.Autoimmune work-up finally led to the diagnosis of SLE,which initially presented as MAS and manifested respiratory failure,although neither bone marrow biopsy nor lymph node biopsy showed hemophagocytosis.To our knowledge,such a scenario has never been reported in detail before.The patient had a favorable reaction to combination treatment with corticosteroid and cyclosporine A and has been in clinical remission during the 1-year follow up period.CONCLUSION Respiratory failure and MAS can be an onset of SLE.Early diagnosis and appropriate treatment are extremely important for a better prognosis.

Role of tumor-associated macrophages in common digestive system malignant tumors

Many digestive system malignant tumors are characterized by high incidence and mortality rate.Increasing evidence has revealed that the tumor microenvironment(TME)is involved in cancer initiation and tumor progression.Tumor-associated macrophages(TAMs)are a predominant constituent of the TME,and participate in the regulation of various biological behaviors and influence the prognosis of digestive system cancer.TAMs can be mainly classified into the antitumor M1 phenotype and protumor M2 phenotype.The latter especially are crucial drivers of tumor invasion,growth,angiogenesis,metastasis,immunosuppression,and resistance to therapy.TAMs are of importance in the occurrence,development,diagnosis,prognosis,and treatment of common digestive system malignant tumors.In this review,we summarize the role of TAMs in common digestive system malignant tumors,including esophageal,gastric,colorectal,pancreatic and liver cancers.How TAMs promote the development of tumors,and how they act as potential therapeutic targets and their clinical applications are also described.

Hydralazine Promotes Central Nervous System Recovery after Spinal Cord Injury by Suppressing Oxidative Stress and Inflammation through Macrophage Regulation

Objective:This study aims to investigate the effects of hydralazine on inflammation induced by spinal cord injury(SCI)in the central nervous system(CNS)and its mechanism in promoting the structural and functional recovery of the injured CNS.Methods:A compressive SCI mouse model was utilized for this investigation.Immunofluorescence and quantitative real-time polymerase chain reaction were employed to examine the levels of acrolein,acrolein-induced inflammation-related factors,and macrophages at the injury site and within the CNS.Western blotting was used to evaluate the activity of the phosphoinositide 3-kinase(PI3K)/AKT pathway to study macrophage regulation.The neuropathic pain and motor function recovery were evaluated by glutamic acid decarboxylase 65/67(GAD65/67),vesicular glutamate transporter 1(VGLUT1),paw withdrawal response,and Basso Mouse Scale score.Nissl staining and Luxol Fast Blue(LFB)staining were performed to investigate the structural recovery of the injured CNS.Results:Hydralazine downregulated the levels of acrolein,IL-1β,and TNF-αin the spinal cord.The downregulation of acrolein induced by hydralazine promoted the activation of the PI3K/AKT pathway,leading to M2 macrophage polarization,which protected neurons against SCI-induced inflammation.Additionally,hydralazine promoted the structural recovery of the injured spinal cord area.Mitigating inflammation and oxidative stress by hydralazine in the animal model alleviated neuropathic pain and altered neurotransmitter expression.Furthermore,hydralazine facilitated motor function recovery following SCI.Nissl staining and LFB staining indicated that hydralazine promoted the structural recovery of the injured CNS.Conclusion:Hydralazine,an acrolein scavenger,significantly mitigated SCI-induced inflammation and oxidative stress in vivo,modulated macrophage activation,and consequently promoted the structural and functional recovery of the injured CNS.

Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/β-catenin pathway modulation to suppress liver cancer

BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway

BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue.Never-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain.AIM To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism.METHODS Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk.Subsequently,blood and urine indexes were assessed,along with examination of renal tissue pathology.Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and Sirius-red.Additionally,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h.In both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and ELISA.RESULTS In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis.Notably,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related factors.Furthermore,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 cells.Additionally,myricetin modulated the M1-type polarization of the RAW 264.7 cells.Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin.The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002.CONCLUSION This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

The roles of macrophage migration inhibitory factor in retinal diseases

Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive immunity.There are some evidences that MIF is involved in many vitreoretinal diseases.For example,MIF can exacerbate many types of uveitis;measurements of MIF levels can be used to monitor the effectiveness of uveitis treatment.MIF also alleviates trauma-induced and glaucoma-induced optic nerve damage.Furthermore,MIF is critical for retinal/choroidal neovascularization,especially complex neovascularization.MIF exacerbates retinal degeneration;thus,anti-MIF therapy may help to mitigate retinal degeneration.MIF protects uveal melanoma from attacks by natural killer cells.The mechanism underlying the effects of MIF in these diseases has been demonstrated:it binds to cluster of differentiation 74,inhibits the c-Jun N-terminal kinase pathway,and triggers mitogen-activated protein kinases,extracellular signal-regulated kinase-1/2,and the phosphoinositide-3-kinase/Akt pathway.MIF also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling pathway.This review focuses on the structure and function of MIF and its receptors,including the effects of MIF on uveal inflammation,retinal degeneration,optic neuropathy,retinal/choroidal neovascularization,and uveal melanoma.

Global trends in publications regarding macrophages-related diabetic foot ulcers in the last two decades

BACKGROUND Diabetic foot ulcers(DFUs)are one of the most severe and popular complications of diabetes.The persistent non-healing of DFUs is the leading cause of amputation,which causes significant mental and financial stress to patients and their families.Macrophages are critical cells in wound healing and perform essential roles in all phases of wound healing.However,no studies have been carried out to systematically illustrate this area from a scientometric point of view.Although there have been some bibliometric studies on diabetes,reports focusing on the investigation of macrophages in DFUs are lacking.AIM To perform a bibliometric analysis to systematically assess the current state of research on macrophage-related DFUs.METHODS The publications of macrophage-related DFUs from January 1,2004,to December 31,2023,were retrieved from the Web of Science Core Collection on January 9,2024.Four different analytical tools:VOSviewer(v1.6.19),CiteSpace(v6.2.R4),HistCite(v12.03.07),and Excel 2021 were used for the scientometric research.RESULTS A total of 330 articles on macrophage-related DFUs were retrieved.The most published countries,institutions,journals,and authors in this field were China,Shanghai Jiao Tong University of China,Wound Repair and Regeneration,and Aristidis Veves.Through the analysis of keyword co-occurrence networks,historical direct citation networks,thematic maps,and trend topics maps,we synthesized the prevailing research hotspots and emerging trends in this field.CONCLUSION Our bibliometric analysis provides a comprehensive overview of macrophage-related DFUs research and insights into promising upcoming research.

Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis

Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous system.Macrophage polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple sclerosis.This study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune encephalomyelitis.We found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6.Crucially,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified macrophages.In addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced inflammation.These findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for multiple sclerosis.