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
In this paper, toll-like receptor expression pattern in monocytes-derived macrophages by lipopolysaccharid （LPS） stimulation was examined. Jugular venous blood samples from 4 Japanese calves were obtained and the pe...In this paper, toll-like receptor expression pattern in monocytes-derived macrophages by lipopolysaccharid （LPS） stimulation was examined. Jugular venous blood samples from 4 Japanese calves were obtained and the peripheral blood mononuclear cells （PBMC） were isolated. The PBMC were cultured for 7 d so as to collect monocytes-derived macrophages in Repcell. The PBMC were stimulated by LPS for 24 h and the mRNA expression pattern of TLR and cytokines in monocytes-derived macrophages （Mod-Mφ） was analyzed. Results showed that LPS stimulation of Mod-Mφ could increase the mRNA levels of the genes of TNF-α, IL-6, and IL-8. In addition, the mRNA levels of the genes of TNF-α and IL-6 in the group of LPS stimulation were most significantly （P 〈 0.01） higher than those in control group and the mRNA levels of TLR1, 3, 5, 8, and 10 were significantly （P 〈 0.05） decreased after LPS stimulation. There was no difference in the mRNA expressions of TLR2, 4, 6, and 7 between the groups of the control and LPS stimulation. Besides, expression of TLR9 was not found. It suggested that monocytes-derived macrophages could respond to LPS and they might take an important role in the innate immunity. The important function of the cells might contribute to better disease treatment.展开更多
Monocyte-derived macrophages(MoMacs)are the most important effector cells that cause pulmonary fibrosis.However,the characteristics of MoMac differentiation in silicosis and the mechanisms by which MoMacs affect the p...Monocyte-derived macrophages(MoMacs)are the most important effector cells that cause pulmonary fibrosis.However,the characteristics of MoMac differentiation in silicosis and the mechanisms by which MoMacs affect the progression of pulmonary fibrosis remain unclear.Integration of single-cell and spatial transcriptomic analyses revealed that the silicosis niche was occupied by a subset of MoMacs,identified as Spp1hiMacs,which remain in an immature transitional state of differentiation during silicosis.This study investigated the mechanistic foundations of mitochondrial damage induced by the lipoprotein-associated phospholipase A2(Lp-PLA2,encoded by Pla2g7)–acyl-CoA:lysocardiolipin acyltransferase-1(ALCAT1)–cardiolipin(CL)signaling pathway,which interferes with Spp1hiMac differentiation.We demonstrated that in SiO_(2)-induced MoMacs,Lp-PLA2 induces abnormal CL acylation through the activation of ALCAT1,resulting in impaired mitochondrial localization of PINK1 and LC3B and mitochondrial autophagy defects.Simultaneously,lysosomal dysfunction causes the release of the lysosomal protein cathepsin B into the cytoplasm,which involves M1 and M2 macrophage polarization and the activation of proinflammatory and profibrotic pathways.Furthermore,we assessed the efficacy of the Lp-PLA2 inhibitor darapladib in ameliorating silica-induced pulmonary fibrosis in a murine model.Our findings enhance our understanding of silicosis pathogenesis and offer promising opportunities for developing targeted therapies to mitigate fibrotic progression and maintain lung function in affected individuals.展开更多
Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macro...Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.展开更多
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
Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neu...Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.展开更多
In this experiment Toll-like receptor expression pattern in monocytes and monocyte-derived macrophages by lipopolysaccharide （LPS） stimulation was examined. Jugular venous blood was collected from four Japanese calv...In this experiment Toll-like receptor expression pattern in monocytes and monocyte-derived macrophages by lipopolysaccharide （LPS） stimulation was examined. Jugular venous blood was collected from four Japanese calves, and the peripheral blood mononuclear cells （PBMCs） were isolated. The cells were directly used for collecting monocytes by magnetic cell sorting or cultured for 7 days to collect monocyte-derived macrophages in Repcell. Then we analyzed the mRNA expression pattern of TLRs and cytokines in monocytes and monocyte-derived macrophages after LPS stimulation for 24 h. LPS stimulation of both monocytes and monocyte-derived macrophages resulted in an increase in the levels of mRNA transcripts for TNF-α IL-6 and IL-8. Moreover, TNF-α and IL-6 mRNA expressions were significantly augmented by LPS stimulation in monocyte-derived macrophages. TLRs mRNA expressions were unchanged after LPS stimulation of monocytes, while TLRs mRNA expressions in monocyte-derived macrophages were complicated. TLR1, 3, 5, 8 and 10 were significantly decreased after LPS stimulation and there were no differences in the mRNA expressions of TLR2, 4, 6 and 7 between the groups of control and LPS stimulation. Besides, no expression of TLR9 was found. As antigen presenting cells, monocytes and monocyte-derived macrophages respond differently to LPS, so they may have different functions in the innate immune system.展开更多
Objective To explore the effects of sulforaphane on Toll-like receptor 4(TLR4)/myeloid differentiation factor88(MyD88)pathway and its downstream inflammatory cytokines in patients with chronic obstructive pulmonary di...Objective To explore the effects of sulforaphane on Toll-like receptor 4(TLR4)/myeloid differentiation factor88(MyD88)pathway and its downstream inflammatory cytokines in patients with chronic obstructive pulmonary disease(COPD).Methods From Jan.2012 to Mar.2013,thirty-two stable COPD patients and thirty healthy donors(non-COPD group)from the First Hospital of Lanzhou University were recruited.The peripheral展开更多
Objective To investigate the effects of telmisartan on the expression of angiotensin converting enzyme 2(ACE2) mRNA in monocyte-derived macrophages of hypertensive patients accompanied with diabetes. Methods 62 essent...Objective To investigate the effects of telmisartan on the expression of angiotensin converting enzyme 2(ACE2) mRNA in monocyte-derived macrophages of hypertensive patients accompanied with diabetes. Methods 62 essential hypertensive patients accompanied展开更多
Schwann cells and macrophages are the main immune cells involved in peripheral nerve injury.After injury,Schwann cells produce an inflammatory response and secrete various chemokines,inflammatory factors,and some othe...Schwann cells and macrophages are the main immune cells involved in peripheral nerve injury.After injury,Schwann cells produce an inflammatory response and secrete various chemokines,inflammatory factors,and some other cytokines to promote the recruitment and M2 polarization of blood-derived macrophages,enhancing their phagocytotic ability,and thus play an important role in promoting nerve regeneration.Macrophages have also been found to promote vascular regeneration after injury,promote the migration and proliferation of Schwann cells along blood vessels,and facilitate myelination and axon regeneration.Therefore,there is a close interaction between Schwann cells and macrophages during peripheral nerve regeneration,but this has not been systematically summarized.In this review,the mechanisms of action of Schwann cells and macrophages in each other's migration and phenotypic transformation are reviewed from the perspective of each other,to provide directions for research on accelerating nerve injury repair.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
Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed t...Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.展开更多
Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and infl...Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.展开更多
Macrophages derived from the human THP-1 cell line have been widely used as substitutes for primary macrophages in various macrophage-related studies.However,difficulties still exist in establishing THP-I macrophage m...Macrophages derived from the human THP-1 cell line have been widely used as substitutes for primary macrophages in various macrophage-related studies.However,difficulties still exist in establishing THP-I macrophage models.This research presents techniques for generating different phenotypes of activated macrophages derived from THP-1 cells by introducing specific stimuli and provides some potential markers to confirm each type of activated macrophage.It is hoped to provide novel and useful methods for scientific research and to help researchers explore this field more intuitively and effectively.展开更多
Senescent macrophages have emerged as dynamic cells within the tumor microenvironment that significantly promote tumor progression through complex cellular and molecular functional alterations. This review explores th...Senescent macrophages have emerged as dynamic cells within the tumor microenvironment that significantly promote tumor progression through complex cellular and molecular functional alterations. This review explores the multifaceted roles of macrophage senescence in cancer, and establishes links between senescent macrophages and tumor progression from multiple perspectives, on the basis of the first comprehensive analysis of the molecular mechanisms and pathways involved. By systematically examining the diverse changes in senescent macrophages, this review integrates and analyzes their effects on tumors, thus offering a comprehensive and novel theoretical foundation, and practical insights for cancer treatment. Notably, by integrating current molecular research and therapeutic advancements, we summarize novel therapeutic strategies targeting senescent macrophages, including senolytics, senescence modulators, and cutting-edge immunotherapies, thereby highlighting the potential of senescent macrophages as a therapeutic target and introducing new opportunities for cancer treatment.展开更多
Pyroptosis is a form of programmed cell death.Excessive or uncontrolled pyroptosis and the production of pro-inflammatory cytokines can lead to organ damage,circulatory failure,and even death.Gasdermin D(GSDMD)is the ...Pyroptosis is a form of programmed cell death.Excessive or uncontrolled pyroptosis and the production of pro-inflammatory cytokines can lead to organ damage,circulatory failure,and even death.Gasdermin D(GSDMD)is the primary executor of pyroptosis in macrophages.Upon cleavage,the N-terminal domain of GSDMD(GSDMD-N)is activated and oligomerizes to form pore-like structures in the plasma membrane,triggering pyroptosis and resulting in the release of pro-inflammatory cytokines such as interleukin-1β(IL-1β).As a key executioner molecule of pyroptosis,Gasdermin D plays a crucial role in pathogen-induced pyroptosis in macrophages.With in-depth research on the function and regulatory mechanisms of GSDMD,its role in pathogen-induced macrophage pyroptosis has gradually been revealed.This article elaborates on the mechanism of GSDMD in pathogen-induced macrophage pyroptosis,providing insights for exploring pyroptosis in the prevention and control of bacterial diseases,and identifying new therapeutic targets for bacterial infections.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
Objectives This study aimed to investigate the impact of foam macrophages(FMs) on the intracellular survival of Mycobacterium tuberculosis(MTB) and identify the molecular mechanisms influencing MTB survival.Methods An...Objectives This study aimed to investigate the impact of foam macrophages(FMs) on the intracellular survival of Mycobacterium tuberculosis(MTB) and identify the molecular mechanisms influencing MTB survival.Methods An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival.Results Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate(cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival.Conclusions FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.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
BACKGROUND Tumor-associated macrophages(TAMs)have demonstrated significant potential as a research and treatment approach for hepatocellular carcinoma(HCC).Nevertheless,a comprehensive quantitative analysis of TAMs in...BACKGROUND Tumor-associated macrophages(TAMs)have demonstrated significant potential as a research and treatment approach for hepatocellular carcinoma(HCC).Nevertheless,a comprehensive quantitative analysis of TAMs in HCC remained insufficient.Therefore,the objective of this study was to employ bibliometric methods to investigate the development trends and research frontiers pertaining to this field.AIM To determine the knowledge structure and current research hotspots by bibliometric analysis of scholarly papers pertaining to TAMs in HCC.METHODS The present study employed the Web of Science Core Collection to identify all papers related to TAMs in HCC research.Utilizing the Analysis Platform of Bibliometrics,CiteSpace 6.2.R4,and Vosviewer 1.6.19,the study conducted a comprehensive analysis encompassing multiple dimensions such as publication quantity,countries of origin,affiliated institutions,publishing journals,contributing authors,co-references,author keywords,and emerging frontiers within this research domain.RESULTS A thorough examination was undertaken on 818 papers within this particular field,published between January 1,1985 to September 1,2023,which has witnessed a substantial surge in scholarly contributions since 2012,with a notable outbreak in 2019.China was serving as the central hub in this field,with Fudan University leading in terms of publications and citations.Chinese scholars have taken the forefront in driving the research expansion within this field.Hepatology emerged as the most influential journal in this field.The study by Qian and Pollard in 2010 received the highest number of co-citations.It was observed that the citation bursts of references coincided with the outbreak of publications.Notably,“tumor microenvironment”,“immunotherapy”,“prognostic”,“inflammation”,and“polarization”,etc.emerged as frequently occurring keywords in this field.Of particular interest,“immune evasion”,“immune infiltration”,and“cancer genome atlas”were identified as emerging frontiers in recent research.CONCLUSION The field of TAMs in HCC exhibited considerable potential,as evidenced by the promising prospects of immunotherapeutic interventions targeting TAMs for the amelioration of HCC.The emerging frontiers in this field primarily revolved around modulating the immunosuppressive characteristics of TAMs within a liver-specific immune environment,with a focus on how to counter immune evasion and reduce immune infiltration.展开更多
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 Natural Science Foundation of China(30871800, 30471259)the National Key Technology R&D Program of China (2006BAD04A03-07)
文摘In this paper, toll-like receptor expression pattern in monocytes-derived macrophages by lipopolysaccharid （LPS） stimulation was examined. Jugular venous blood samples from 4 Japanese calves were obtained and the peripheral blood mononuclear cells （PBMC） were isolated. The PBMC were cultured for 7 d so as to collect monocytes-derived macrophages in Repcell. The PBMC were stimulated by LPS for 24 h and the mRNA expression pattern of TLR and cytokines in monocytes-derived macrophages （Mod-Mφ） was analyzed. Results showed that LPS stimulation of Mod-Mφ could increase the mRNA levels of the genes of TNF-α, IL-6, and IL-8. In addition, the mRNA levels of the genes of TNF-α and IL-6 in the group of LPS stimulation were most significantly （P 〈 0.01） higher than those in control group and the mRNA levels of TLR1, 3, 5, 8, and 10 were significantly （P 〈 0.05） decreased after LPS stimulation. There was no difference in the mRNA expressions of TLR2, 4, 6, and 7 between the groups of the control and LPS stimulation. Besides, expression of TLR9 was not found. It suggested that monocytes-derived macrophages could respond to LPS and they might take an important role in the innate immunity. The important function of the cells might contribute to better disease treatment.
基金supported by the National Key Technologies R&D Program of China(No.2021YFC2500700)the National Natural Science Foundation of China(No.82003406)+2 种基金the Natural Science Foundation of Hebei Province(H2022209073)the China Postdoctoral Science Foundation(2023M733985)the CAMS Institute of Respiratory Medicine Grant for Young Scholars(2023-ZF-69).
文摘Monocyte-derived macrophages(MoMacs)are the most important effector cells that cause pulmonary fibrosis.However,the characteristics of MoMac differentiation in silicosis and the mechanisms by which MoMacs affect the progression of pulmonary fibrosis remain unclear.Integration of single-cell and spatial transcriptomic analyses revealed that the silicosis niche was occupied by a subset of MoMacs,identified as Spp1hiMacs,which remain in an immature transitional state of differentiation during silicosis.This study investigated the mechanistic foundations of mitochondrial damage induced by the lipoprotein-associated phospholipase A2(Lp-PLA2,encoded by Pla2g7)–acyl-CoA:lysocardiolipin acyltransferase-1(ALCAT1)–cardiolipin(CL)signaling pathway,which interferes with Spp1hiMac differentiation.We demonstrated that in SiO_(2)-induced MoMacs,Lp-PLA2 induces abnormal CL acylation through the activation of ALCAT1,resulting in impaired mitochondrial localization of PINK1 and LC3B and mitochondrial autophagy defects.Simultaneously,lysosomal dysfunction causes the release of the lysosomal protein cathepsin B into the cytoplasm,which involves M1 and M2 macrophage polarization and the activation of proinflammatory and profibrotic pathways.Furthermore,we assessed the efficacy of the Lp-PLA2 inhibitor darapladib in ameliorating silica-induced pulmonary fibrosis in a murine model.Our findings enhance our understanding of silicosis pathogenesis and offer promising opportunities for developing targeted therapies to mitigate fibrotic progression and maintain lung function in affected individuals.
基金supported by Qingdao Key Medical and Health Discipline ProjectThe Intramural Research Program of the Affiliated Hospital of Qingdao University,No. 4910Qingdao West Coast New Area Science and Technology Project,No. 2020-55 (all to SW)。
文摘Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.
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Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),project numbers 324633948 and 409784463(DFG grants Hi 678/9-3 and Hi 678/10-2,FOR2953)to HHBundesministerium für Bildung und Forschung-BMBF,project number 16LW0463K to HT.
文摘Microglia are the resident macrophages of the central nervous system.They act as the first line of defense against pathogens and play essential roles in neuroinflammation and tissue repair after brain insult or in neurodegenerative and demyelinating diseases(Borst et al.,2021).Together with infiltrating monocyte-derived macrophages,microglia also play a critical role for brain tumor development,since immunosuppressive interactions between tumor cells and tumor-associated microglia and macrophages(TAM)are linked to malignant progression.This mechanism is of particular relevance in glioblastoma(GB),the deadliest form of brain cancer with a median overall survival of less than 15 months(Khan et al.,2023).Therefore,targeting microglia and macrophage activation is a promising strategy for therapeutic interference in brain disease.
文摘In this experiment Toll-like receptor expression pattern in monocytes and monocyte-derived macrophages by lipopolysaccharide （LPS） stimulation was examined. Jugular venous blood was collected from four Japanese calves, and the peripheral blood mononuclear cells （PBMCs） were isolated. The cells were directly used for collecting monocytes by magnetic cell sorting or cultured for 7 days to collect monocyte-derived macrophages in Repcell. Then we analyzed the mRNA expression pattern of TLRs and cytokines in monocytes and monocyte-derived macrophages after LPS stimulation for 24 h. LPS stimulation of both monocytes and monocyte-derived macrophages resulted in an increase in the levels of mRNA transcripts for TNF-α IL-6 and IL-8. Moreover, TNF-α and IL-6 mRNA expressions were significantly augmented by LPS stimulation in monocyte-derived macrophages. TLRs mRNA expressions were unchanged after LPS stimulation of monocytes, while TLRs mRNA expressions in monocyte-derived macrophages were complicated. TLR1, 3, 5, 8 and 10 were significantly decreased after LPS stimulation and there were no differences in the mRNA expressions of TLR2, 4, 6 and 7 between the groups of control and LPS stimulation. Besides, no expression of TLR9 was found. As antigen presenting cells, monocytes and monocyte-derived macrophages respond differently to LPS, so they may have different functions in the innate immune system.
文摘Objective To explore the effects of sulforaphane on Toll-like receptor 4(TLR4)/myeloid differentiation factor88(MyD88)pathway and its downstream inflammatory cytokines in patients with chronic obstructive pulmonary disease(COPD).Methods From Jan.2012 to Mar.2013,thirty-two stable COPD patients and thirty healthy donors(non-COPD group)from the First Hospital of Lanzhou University were recruited.The peripheral
文摘Objective To investigate the effects of telmisartan on the expression of angiotensin converting enzyme 2(ACE2) mRNA in monocyte-derived macrophages of hypertensive patients accompanied with diabetes. Methods 62 essential hypertensive patients accompanied
基金supported by the Natural Science Foundation of Shandong Province,China(81072398).
文摘Schwann cells and macrophages are the main immune cells involved in peripheral nerve injury.After injury,Schwann cells produce an inflammatory response and secrete various chemokines,inflammatory factors,and some other cytokines to promote the recruitment and M2 polarization of blood-derived macrophages,enhancing their phagocytotic ability,and thus play an important role in promoting nerve regeneration.Macrophages have also been found to promote vascular regeneration after injury,promote the migration and proliferation of Schwann cells along blood vessels,and facilitate myelination and axon regeneration.Therefore,there is a close interaction between Schwann cells and macrophages during peripheral nerve regeneration,but this has not been systematically summarized.In this review,the mechanisms of action of Schwann cells and macrophages in each other's migration and phenotypic transformation are reviewed from the perspective of each other,to provide directions for research on accelerating nerve injury repair.
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the support of the National Natural Science Foundation of China (Grant No.82272503)Natural Science Foundation of Zhejiang Province (Grant No. LQN25H060006)
文摘Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.
基金supported by grants from National Natural Science Foundation of China(32125038)National Key Research and Development Program of China(grant number 2023YFD1801100 and 2023YFD1800804)+1 种基金the Key Research and Development Program of the Xinjiang Uygur Autonomous Region(No.2024B02016)the 2115 Talent Development Program of China Agricultural University.
文摘Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.
基金supported by the Shaanxi University of Chinese Medicine-National Natural Science Foundation Cultivation Project(No.2023GP16)the Shaanxi Key Laboratory of Research on TCM Physical Constitution and Diseases Prevention and Treatment(No.KF202311)the Graduate Student Innovative Practical Ability Improvement Project(No.CXSJ202302),China.
文摘Macrophages derived from the human THP-1 cell line have been widely used as substitutes for primary macrophages in various macrophage-related studies.However,difficulties still exist in establishing THP-I macrophage models.This research presents techniques for generating different phenotypes of activated macrophages derived from THP-1 cells by introducing specific stimuli and provides some potential markers to confirm each type of activated macrophage.It is hoped to provide novel and useful methods for scientific research and to help researchers explore this field more intuitively and effectively.
基金supported by grants from the Postdoctoral Science Foundation of China (Grant No. 2020M672072)。
文摘Senescent macrophages have emerged as dynamic cells within the tumor microenvironment that significantly promote tumor progression through complex cellular and molecular functional alterations. This review explores the multifaceted roles of macrophage senescence in cancer, and establishes links between senescent macrophages and tumor progression from multiple perspectives, on the basis of the first comprehensive analysis of the molecular mechanisms and pathways involved. By systematically examining the diverse changes in senescent macrophages, this review integrates and analyzes their effects on tumors, thus offering a comprehensive and novel theoretical foundation, and practical insights for cancer treatment. Notably, by integrating current molecular research and therapeutic advancements, we summarize novel therapeutic strategies targeting senescent macrophages, including senolytics, senescence modulators, and cutting-edge immunotherapies, thereby highlighting the potential of senescent macrophages as a therapeutic target and introducing new opportunities for cancer treatment.
基金Foshan High-Level Talent and Lingnan Scholar Research Initiation Project(Project No.:CGZ07001)Foshan Science and Technology Innovation Project(Project No.:2420001004253)Foshan Self-Funded Science and Technology Innovation Project(Project No.:2420001004253)。
文摘Pyroptosis is a form of programmed cell death.Excessive or uncontrolled pyroptosis and the production of pro-inflammatory cytokines can lead to organ damage,circulatory failure,and even death.Gasdermin D(GSDMD)is the primary executor of pyroptosis in macrophages.Upon cleavage,the N-terminal domain of GSDMD(GSDMD-N)is activated and oligomerizes to form pore-like structures in the plasma membrane,triggering pyroptosis and resulting in the release of pro-inflammatory cytokines such as interleukin-1β(IL-1β).As a key executioner molecule of pyroptosis,Gasdermin D plays a crucial role in pathogen-induced pyroptosis in macrophages.With in-depth research on the function and regulatory mechanisms of GSDMD,its role in pathogen-induced macrophage pyroptosis has gradually been revealed.This article elaborates on the mechanism of GSDMD in pathogen-induced macrophage pyroptosis,providing insights for exploring pyroptosis in the prevention and control of bacterial diseases,and identifying new therapeutic targets for bacterial infections.
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supported by the Beijing Natural Science Foundation (grant number: 7232060)National Key Research and Development Program of China (grant number: 2023YFC2307301)Top Level Public Health Technical Personnel Training Plan (grant number: LJRC-03-09)。
文摘Objectives This study aimed to investigate the impact of foam macrophages(FMs) on the intracellular survival of Mycobacterium tuberculosis(MTB) and identify the molecular mechanisms influencing MTB survival.Methods An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival.Results Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate(cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival.Conclusions FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
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 Sanming Project of Medicine in Shenzhen,No.SZZYSM202111002Shenzhen Medical Research Fund,No.B2302008+1 种基金Shenzhen Science and Technology Program,No.JCYJ20220531091809022,No.JSGG20210802093208023,No.JCYJ20220818103402006,and No.ZDSYS201606081515458Traditional Chinese Medicine Bureau of Guangdong Province,No.20231286.
文摘BACKGROUND Tumor-associated macrophages(TAMs)have demonstrated significant potential as a research and treatment approach for hepatocellular carcinoma(HCC).Nevertheless,a comprehensive quantitative analysis of TAMs in HCC remained insufficient.Therefore,the objective of this study was to employ bibliometric methods to investigate the development trends and research frontiers pertaining to this field.AIM To determine the knowledge structure and current research hotspots by bibliometric analysis of scholarly papers pertaining to TAMs in HCC.METHODS The present study employed the Web of Science Core Collection to identify all papers related to TAMs in HCC research.Utilizing the Analysis Platform of Bibliometrics,CiteSpace 6.2.R4,and Vosviewer 1.6.19,the study conducted a comprehensive analysis encompassing multiple dimensions such as publication quantity,countries of origin,affiliated institutions,publishing journals,contributing authors,co-references,author keywords,and emerging frontiers within this research domain.RESULTS A thorough examination was undertaken on 818 papers within this particular field,published between January 1,1985 to September 1,2023,which has witnessed a substantial surge in scholarly contributions since 2012,with a notable outbreak in 2019.China was serving as the central hub in this field,with Fudan University leading in terms of publications and citations.Chinese scholars have taken the forefront in driving the research expansion within this field.Hepatology emerged as the most influential journal in this field.The study by Qian and Pollard in 2010 received the highest number of co-citations.It was observed that the citation bursts of references coincided with the outbreak of publications.Notably,“tumor microenvironment”,“immunotherapy”,“prognostic”,“inflammation”,and“polarization”,etc.emerged as frequently occurring keywords in this field.Of particular interest,“immune evasion”,“immune infiltration”,and“cancer genome atlas”were identified as emerging frontiers in recent research.CONCLUSION The field of TAMs in HCC exhibited considerable potential,as evidenced by the promising prospects of immunotherapeutic interventions targeting TAMs for the amelioration of HCC.The emerging frontiers in this field primarily revolved around modulating the immunosuppressive characteristics of TAMs within a liver-specific immune environment,with a focus on how to counter immune evasion and reduce immune infiltration.
