Macrophage Polarization Research Articles

High glucose induces pro-inflammatory polarization of macrophages by inhibiting immune-responsive gene 1 expression.

To investigate the effect of high glucose on macrophage polarization and the role of immune-responsive gene 1 (IRG1) in mediating its effect. RAW264.7 cells were transfected with IRG1-overexpressing plasmid or IRG1 siRNA via electroporation and cultured in either normal or high glucose for 72 h to observe the changes in cell viability and morphology using CCK-8 assay and phase contrast microscopy. The protein levels of IRG1, iNOS, Arg-1, IL-1β and IL-10 in the treated cells were detected with Western blotting, and the fluorescence intensities of iNOS and Arg-1 were detected using immunofluorescence assay. The protein levels of IL-1β and IL-10 in the culture medium were determined with ELISA. High glucose exposure significantly reduced IRG1 and Arg-1 expressions, increased iNOS and IL-1β expressions and IL-1β secretion, and decreased IL-10 level in RAW264.7 cells. Transfection with the IRG1-overexpressing plasmid provided the cells with obvious resistance to high glucose-induced changes in iNOS, Arg-1, IL-1β and IL-10, whereas IRG1 knockdown further enhanced the effects of high glucose exposure on Arg-1 expression and the expression and secretion of IL-10. High glucose promotes M1 polarization of the macrophages possibly through a mechanism to inhibit the expression of IRG1 protein, thus leading to chronic inflammatory response.

Hirsutella sinensis Fungus Promotes CD8+ T Cell-Mediated Anti-Tumor Immunity by Affecting Tumor-Associated Macrophages-Derived CCRL2

ABSTRACT Introduction Hirsutella sinensis fungus (HSF)is an artificial substitute for Cordyceps sinensis and has shown promising therapeutic effects in various diseases including cancer. Previous studies have demonstrated that HSF can affect macrophage polarization and activate systemic immune response. In our preliminary experiments, we validated that HSF inhibited the proliferation of lung cancer (LC) cells, but the underlying mechanism is elusive. We intended to explore the mechanism of HSF in promoting anti-tumor immunity. Methods In vivo experiments were performed to confirm inhibitory effect of HSF on LC growth, and sequencing results revealed abnormal expression of CCRL2. Knockdown and overexpression of CCRL2 were conducted to investigate its effect on macrophage polarization, and co-culture with T cells was to assay the impact of HSF+CCRL2 on CD8+ T cell activation by flow cytometry. Results Overexpression of CCRL2 promoted macrophage polarization toward M1 and activated the proliferation and effector function of CD8+ T cells. HSF promoted CCRL2 expression and affected M1 polarization via CCRL2, which in turn affected CD8+ T cell-mediated anti-tumor immunity. Discussion Our study demonstrated that HSF promoted macrophage M1 polarization and activated CD8+ T cells via CCRL2, thereby inhibiting the progression of LC.

Relevance of superoxide dismutase type 1 to lipoid pneumonia: the first retrospective case-control study

BackgroundLipoid pneumonia (LP) is a rare disease caused by the accumulation of lipids and lipid-laden macrophages in the alveoli inducing damage. LP is difficult to differentiate from other similar diseases without pathological evidence, such as upper respiratory tract infection (URTI), pneumonia, cryptogenic organizing pneumonia (COP), pulmonary alveolar proteinosis (PAP), lung mucinous adenocarcinoma and pulmonary edema. Given the high misdiagnosis rate and limited statistical clinical and treatment data, there is an urgent need for novel indicators of LP. Superoxide dismutase type1 (SOD1) plays an essential role in macrophage polarization, promoting inflammation and oxidative stress, but its association with LP remains unknown.MethodsThe clinical data of 22 patients with proven LP from January 2008 to June 2024 and their prognostic information up to June 2024 were retrospectively gathered (ClinicalTrials.gov, NCT06430008). Additionally, information on patients with URTI, bacterial and fungal pneumonia, COP, PAP, lung mucinous adenocarcinoma and pulmonary edema, was collected totaling 140 patients as control subjects. Receiver operating characteristic curve, machine learning (ML), regression and survival analyses were performed to analyze the data.ResultsIn multivariate regression analysis, the sole independent risk factor of LP was the level of SOD1 (OR 0.922, 95% CI: 0.878 ~ 0.967, P < 0.001), while smoking status (β= -0.177, 95% CI -18.645~-2.836, P = 0.008), diabetes mellitus (β= -0.191, 95% CI: -20.442~-3.592, P = 0.005), and total sialic acid (TSA) (β= -0.426, 95% CI: -0.915~ -0.433, P < 0.001) independently influenced the level of SOD1. SOD1 had the highest importance score in ML-based LP predictive models. Additionally, advanced age may be associated with higher mortality in LP.ConclusionSOD1 is a potential biomarker for LP, but the smoking status, diabetes comorbidities, and TSA level need to be considered.

B cells recruitment promotes M2 macrophage polarization to inhibit inflammation during wound healing.

Wound healing causes heavy economic burdens for families and society, becoming a critical issue in the global healthcare system. While the role of immune cells in the wound healing process is well-established, the involvement of B cells remains poorly understood. This study aims to elucidate the essentiality of B cells in wound repair. Our findings demonstrate a rise in B cell population during the early stage of wound healing, which further intensifies during the later stage. We employed anti-CD20 antibodies to deplete B cells in mice and created a whole skin excisional wound mice model, analyzing wound closure over 12 days. B cells were isolated from the animals' spleen and co-cultured with macrophages from bone marrow. The polarization of M1 and M2 macrophages was analyzed by real-time qPCR and flow cytometry. The wound healing process in mice was observed to be considerably delayed following the elimination of B cells. The wounds exhibited a state of inflammation primarily characterized by the presence of pro-inflammatory M1 macrophages. The decrease in M2 macrophages within the local wound area resulted in impairment of the wound repair mechanism. B cell-macrophage co-culture system revealed that B cells effectively induce the polarization of macrophages towards M2-like phenotype. Furthermore, we found that follicular B cells play predominant role in modulating the polarization of M2 macrophages. Consequently, our findings indicate that B cells can be recruited to the wound site and facilitate the polarization of M2-like macrophages, thereby accelerating the healing process during wound healing.

Innovative treatment of age-related hearing loss using MSCs and EVs with Apelin

Utilizing single-cell transcriptome sequencing (scRNA-seq) technology, this study explores the viability of employing mesenchymal stem cells (MSCs) as a therapeutic approach for age-related hearing loss (ARHL). The research demonstrates MSCs' ability to differentiate into inner ear cell subpopulations, particularly hair cells, delivering Apelin via extracellular vesicles (EVs) to promote M2 macrophage polarization. In vitro experiments show reduced inflammation and preservation of hair cell health. In elderly mice, MSCs transplantation leads to hair cell regeneration, restoring auditory function. These findings highlight the regenerative capabilities of MSCs and EV-mediated therapeutic approaches for ARHL.

IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for immunosuppression

IgG4-mediated M2 macrophage polarization in tertiary lymphoid structures of esophageal cancer: implications for immunosuppression

Increased pro-SFTPB in HDL promotes the pro-inflammatory transition of HDL and represents a sign of poor prognosis in ARDS patients

BackgroundAcute respiratory distress syndrome (ARDS) is causatively associated with excessive alveolar inflammation involving deregulated pro-inflammatory macrophage polarization. High-density lipoprotein (HDL) showed critical anti-inflammatory roles by modulating macrophage function, and its adverse transition to pro-inflammation has an important role in the pathogenesis of ARDS. However, the relationship between HDL protein constituents and functional remodeling is unknown in ARDS.MethodsProteomic techniques were applied to examine the protein profile changes in HDL from septic-ARDS patients versus HDL from healthy controls across two distinct cohorts: a discovery cohort (8 patients and 8 healthy controls) and a validation cohort (22 patients and 10 healthy controls). The changed components significantly associated with prognosis were identified. Luminex assessed the levels of 38 plasma cytokines and chemokines. The in vitro constructed pro-SFTPB enriched HDL was applied to confirm the effect on M1 polarization of THP1-derived macrophage.Results18 proteins were validated from 102 changed HDL proteins identified in the discovery cohort, including HDL particle components, such as apolipoproteins, pro-inflammatory substances known as serum amyloid As (SAAs), and anti-oxidative proteins like paraoxonases (PONs). Among these proteins, only the increase of pro-SFTPB in HDL was significantly associated with poor prognosis of ARDS patients. Notably, HDL-pro-SFTPB level was correlated with plasma pro-inflammatory cytokines and chemokines levels. The correlation assay of pro-SFTPB with other HDL components showed that it was positively and negatively correlated with SAA2 and PON3, respectively. Furthermore, the in vitro studies confirmed that the pro-SFTPB enriched HDL significantly promoted M1 polarization of monocyte-derived macrophages.ConclusionsThe increase of HDL-pro-SFTPB promotes HDL pro-inflammatory transition during septic ARDS, leading to exacerbated progression of ARDS through enhancing M1 macrophage polarization. HDL-pro-SFTPB could be a useful prognostic biomarker for septic ARDS.

Rod‐Shaped Microgel Scaffolds with Interconnective Pores and Oxygen‐generating Functions Promote Skin Wound Healing and Alleviate Hypertrophic Scar Formation

AbstractThe processes of skin wound healing and scar formation are complex, often involving hypoxia and inflammation, which create a pathological microenvironment that impedes normal healing. Improving wound oxygenation and reducing inflammation are crucial for accelerating healing and reducing scarring. Traditional dressings like sponges, gauze, and hydrogels struggle to balance moisture retention, breathability, and exudate absorption. To address these challenges, rod‐shaped microgel scaffolds with larger surface areas and interconnected porous structures are explored to enhance gas transport, promoting wound oxygenation and moisture retention, thus accelerating healing and reducing scarring. Nanoparticles (NPs) are used to mediate the formation of microgels‐assembled scaffold and to load catalase (CAT) for enhanced bioactivity. In vitro experiments showed that this material alleviated oxidative stress and reduced the activity of hypoxia‐inducible factor‐1α (HIF‐1α), nuclear factor kappa B (NF‐κB), and the downstream transforming growth factor‐β1 (TGF‐β)/Smad pathway in fibroblasts. The incorporation of CAT showed a significant promotion of M2‐phenotype macrophage polarization. In vivo studies on rat and rabbit wounds demonstrated that the microgel scaffolds significantly improved exudate absorption and breathability, maintaining a moist and oxygenated environment. These scaffolds reduced tissue hypoxia, accelerated wound healing, and decreased hypertrophic scar formation in vivo. This innovative method leveraged the unique properties of microgels to effectively enhance skin tissue regeneration.

Framework Nucleic Acid-Based and Neutrophil-Based Nanoplatform Loading Baicalin with Targeted Drug Delivery for Anti-Inflammation Treatment.

Targeted drug delivery is a promising strategy for treating inflammatory diseases, with recent research focusing on the combination of neutrophils and nanomaterials. In this study, a targeted nanodrug delivery platform (Ac-PGP-tFNA, APT) was developed using tetrahedral framework nucleic acid (tFNA) along with a neutrophil hitchhiking mechanism to achieve precise delivery and anti-inflammatory effects. The tFNA structure, known for its excellent drug-loading capacity and cellular uptake efficiency, was used to carry a therapeutic agent─baicalin. The results demonstrate that the development of this drug delivery platform not only considerably enhances the bioavailability and effective concentration of the drug (baicalin) but also promotes the polarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages by modulating the interactions between the neutrophils and macrophages. This targeted therapeutic method effectively treats inflammatory conditions such as sepsis and introduces a strategy for managing inflammatory diseases characterized by neutrophil infiltration.

Extracellular peroxiredoxin 6 released from alveolar epithelial cells as a DAMP drives macrophage activation and inflammatory exacerbation in acute lung injury.

Acute respiratory distress syndrome (ARDS) is featured with acute lung inflammatory injury. Our prospective study found that higher levels of peroxiredoxin 6(PRDX6) were detected in bronchoalveolar lavage (BAL) fluid from ARDS patients. Elevated PRDX6 was also correlated with monocytic activation and poor prognosis in ARDS patients. To investigate the origin of extracellular PRDX6, we conducted in vitro and in vivo experiments, demonstrating that PRDX6 can be actively released from alveolar epithelial cells under stress conditions. Our study demonstrated that it could be released from injured lung epithelial cells into the bronchoalveolar interstitial space in mice with acute lung injury and in vitro experiments. Moreover, exogenous PRDX6 was shown to activate the TLR4/NF-κB signalling pathway and induce M1 polarization of macrophages. Notably, the inflammatory effects of PRDX6 were mitigated by specific inhibition of the TLR4 (Toll-like receptor 4)-MD2 (Myeloid differentiation factor 2) complex. Using molecular docking simulations and in vitro binding assays, we confirmed a direct interaction between PRDX6 and MD2, further supporting its role as a damage-associated molecular patterns (DAMP) in ARDS. Our findings suggest that extracellular PRDX6 in bronchoalveolar lavage fluid could be a new DAMP factor in ALI, providing new insights into the pathogenesis of secondary hit in ALI/ARDS and highlighting PRDX6 as a potential therapeutic target for mitigating lung inflammation.

Nerve-Derived Extracellular Matrix Promotes Neural Differentiation of Bone Marrow Stromal Cells and Enhances Interleukin-4 Efficacy for Advanced Nerve Regeneration.

Facilitating neuronal differentiation of stem cells and microenvironment remodeling are the key challenges in cell-based transplantation strategies for central nervous system regeneration. Herein, the study harnesses the intrinsic pro-neural differentiation potential of nerve-derived extracellular matrix (NDEM) and its specific affinity for cytokines to develop an NDEM-gelatin methacryloyl(gelMA)-based bifunctional hydrogel delivery system for stem cells and cytokines. This system promotes the neural differentiation of bone marrow stromal cells (BMSCs) and optimizes the therapeutic index of Interleukin-4 (IL-4) for spinal cord injury (SCI) treatment. It is observed that incorporating NDEM into the hydrogel system intrinsically promotes BMSC differentiation into neuron-like cells and effectively regulates IL-4 release kinetics to match the neural reconstructing timeframe. Further analysis reveals that trace amounts of endogenous basic fibroblast growth factor (bFGF) detected in NDEM exhibit a potent effect in promoting neural differentiation. The sustained release of IL-4 from the NDEM significantly encourages macrophage polarization toward the M2 phase, optimizing the transplant microenvironment throughout the reconstruction process. This study demonstrates an NDEM-based optimization strategy for hybrid hydrogel to achieve synchronized delivery of stem cells and cytokines in regenerative medicine applications.

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

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. To examine the relevant literature on macrophage polarization in DFU healing. 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. 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. 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.

Ag85B-Induced M1 Macrophage Polarization via the TLR4/TRAF6/NF-κB Axis Leading to Bronchial Epithelial Cell Damage and TH17/Treg Imbalance.

Antigen 85B (Ag85B) is a signature antigen of Mycobacterium tuberculosis (MTB). In this study, we aimed to investigate the impact of macrophages stimulated with Ag85B on bronchial epithelial cells and T cells, as well as the underlying mechanisms involved. We used Ag85B to stimulate macrophage and investigated the impact of Ag85B on macrophage polarization. We assessed the impact of TLR4 on Ag85Bmediated macrophage polarization by silencing TLR4. Additionally, the regulatory role of TLR4 on the TRAF6/NF-κB pathway was evaluated through immunoblotting. Activated macrophages with Ag85B were co-cultured with bronchial epithelial cells and T cells, respectively. Through immunoblotting quantification, biochemical methods, and flow cytometry, we explored the effects and molecular mechanisms of Ag85B-induced macrophage activation on bronchial epithelial cell damage and T-cell transformation. In macrophages stimulated with Ag85B, levels of M1 polarization-related genes (CXCL9, CXCL10, and iNOS) and cytokines (IL-6, TNF-α, IL-1β, and IL-12) were increased, and the M1/M2 ratio was elevated. TLR4 silence inhibited the effects of Ag85B on macrophages and decreased TRAF6 and p-NF-κB/NF-κB levels. TRAF6 overexpression reversed the inhibitory effect of TLR4 on macrophage stimulation with Ag85B. After co-culturing with macrophages induced by Ag85B, MBEC cell proliferation was inhibited, apoptosis was promoted, and the TH17/Treg ratio of T cells was increased. Silencing TLR4 reversed the impact of Ag85B-induced macrophage polarization on bronchial epithelial cells and T cells, which was further reversed by TRAF6 overexpression. Ag85B promoted M1 polarization in macrophages through the TLR4/TRAF6/NF-κB axis, resulting in bronchial epithelial cell damage and an imbalance in TH17/Treg cells.

Facile Formulation of a Resveratrol-Mediated Multibond Network Hydrogel with Efficient Sustainable Antibacterial, Reactive Oxygen Species Scavenging, Pro-Angiogenesis, and Immunomodulation Activities for Accelerating Infected Wound Healing.

The management of chronic infected wounds remains a significant clinical challenge, largely due to the deficiency of optimal wound dressings with adequate mechanical strength, appropriate adhesiveness, and efficient sustainable antibacterial, reactive oxygen species (ROS) scavenging, pro-angiogenesis, and immunomodulation properties. To address such a dilemma, we employed a simple and facile strategy to utilize resveratrol (RSV) as a functional component to mediate hydrogel gelation in this study. The structure of this obtained hydrogel was supported by a multibond network, which not only endowed the resultant product with superior mechanical strength and moderate adhesiveness but also effectively prolonged the bioavailability of RSV. This strategy successfully integrated the entire system with sustainable antibacterial, ROS scavenging, pro-angiogenesis, and immunomodulation properties. Subsequent in vivo evidence has verified that this material was capable to accelerate the healing of chronic infected wounds. The underlying mechanism can be explained that this hydrogel is capable of propelling macrophage polarization from the M1 to M2 phenotype through modulating the PI3K/AKT signaling pathway to activate the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling as well as maintaining the mitochondrial membrane potential level in the normal state under excessive inflammatory and oxidative stimulus. In summary, this multifunctional hydrogel wound dressing provides a feasible way to promote the bioavailability of RSV, which is conducive for preparing a promising candidate for chronic infected wound healing. What is more important, it is also beneficial to reveal the correlative mechanisms to establish advanced therapeutic platform for targeting other complex infection microenvironment.

Multi-omic analysis of chronic myelomonocytic leukemia monocytes reveals metabolic and immune dysregulation leading to altered macrophage polarization.

Multi-omic analysis of chronic myelomonocytic leukemia monocytes reveals metabolic and immune dysregulation leading to altered macrophage polarization.

Therapeutic Potential of Vanillic Acid in Ulcerative Colitis Through Microbiota and Macrophage Modulation.

This study investigated the protective effects of the dietary polyphenol vanillic acid (VA) on dextran sulfate sodium-induced acute ulcerative colitis (UC) in mice, focusing on its impact on the gut microbiota and inflammatory responses. VA was supplemented following dextran sulfate sodium administration, and key indicators, including body weight, disease activity index, colon length, spleen index, and inflammatory markers, were assessed. VA supplementation significantly alleviated UC symptoms, preserved intestinal barrier integrity, and reduced pro-inflammatory cytokine levels. Additionally, VA positively altered the gut microbiota composition, promoting beneficial bacteria such as Akkermansia muciniphila while suppressing the arachidonic acid metabolism pathway. Fecal microbiota transplantation confirmed that the VA-modified gut microbiota contributed to these protective effects. VA also facilitated macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, further mitigating inflammation. These findings highlight the potential of VA as a natural dietary intervention for UC, emphasizing its role in regulating the gut microbiota and inflammatory pathways, which may have significant nutritional relevance in managing inflammatory bowel diseases.

Network pharmacology and multi-omics validation of the Jianpi-Yishen formula in the treatment of chronic kidney disease

ObjectiveChronic kidney disease (CKD) is a major global health problem. In clinical practice, the Chinese patent herbal medicine Jianpi-Yishen (JPYS) formula is commonly used to treat CKD. However, the molecular mechanisms by which JPYS targets and modulates the host immune response remain unclear.MethodsThis study utilized network pharmacology, RNA sequencing (RNA-seq), and metabolic analyses using in vivo and in vitro models to investigate the impact of the JPYS formula on inflammation and the immune system. Specifically, the study focused on macrophage polarization and metabolic changes that may slow down the progression of CKD.ResultsA total of 14,946 CKD-related targets were identified from the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases through network pharmacology analyses. 227 potential targets of the JPYS formula were predicted using the TCMSP database. Additionally, network diagram demonstrated that 11 targets were associated with macrophage activity. In vivo studies indicated that the JPYS formula could reduce blood urea nitrogen and serum creatinine in adenine-induced CKD rats. Furthermore, the formula inhibited inflammatory damage and abnormal macrophage infiltration in this CKD model. RNA-seq, proteomic and metabolic analyses identified the regulation of amino acid metabolism by betaine, specifically referring to glycine, serine, and threonine metabolism, as a key target of the JPYS formula in slowing the progression of CKD. In addition, in vitro studies suggested that JPYS may enhance tryptophan metabolism in M1 macrophage polarization and betaine metabolism in M2 macrophage polarization.ConclusionsThe JPYS formula has been shown to have beneficial impact on CKD; a key mechanism is the mitigation of inflammatory damage through the interaction between amino acid metabolism and macrophage polarization. Of specific importance in this context are the roles of tryptophan in M1 polarization and betaine in M2 polarization.

A mechanically stimulated co-culture in 3D composite scaffolds promotes osteogenic and anti-osteoclastogenic activity and M2 macrophage polarization

A mechanically stimulated co-culture in 3D composite scaffolds promotes osteogenic and anti-osteoclastogenic activity and M2 macrophage polarization

Integrating single-cell RNA-seq and bulk RNA-seq to explore prognostic value and immune landscapes of methionine metabolism-related signature in breast cancer

BackgroundNeoadjuvant, endocrine, and targeted therapies have significantly improved the prognosis of breast cancer (BC). However, due to the high heterogeneity of cancer, some patients cannot benefit from existing treatments. Increasing evidence suggests that amino acids and their metabolites can alter the tumor malignant behavior through reshaping tumor microenvironment and regulation of immune cell function. Breast cancer cell lines have been identified as methionine-dependent, and methionine restriction has been proposed as a potential cancer treatment strategy.MethodsWe integrated transcriptomic and single-cell RNA sequencing (ScRNA-seq) analyses based on The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) datasets. Then we applied weighted gene co-expression network analysis (WGCNA) and Cox regression to evaluate methionine metabolism-related genes (MRGs) in BC, constructing and validating a prognostic model for BC patients. Immune landscapes and immunotherapy were further explored. Finally, in vitro experiments were conducted to assess the expression and function of key genes APOC1.ResultsIn this study, we established and validated a prognostic signature based on eight methionine-related genes to predict overall survival (OS) in BC patients. Patients were further stratified into high-risk and low-risk groups according to prognostic risk score. Further analysis revealed significant differences between two groups in terms of pathway alterations, immune microenvironment characteristics, and immune checkpoint expression. Our study shed light on the relationship between methionine metabolism and immune infiltration in BC. APOC1, a key gene in the prognostic signature, was found to be upregulated in BC and closely associated with immune cell infiltration. Notably, APOC1 was primarily expressed in macrophages. Subsequent in vitro experiments demonstrated that silencing APOC1 reduced the generation of tumor-associated macrophages (TAMs) with an M2 phenotype while significantly decreasing the proliferation, invasion, and migration of MDA-MB-231 and MDA-MB-468 breast cancer cell lines.ConclusionWe established a prognostic risk score consisting of genes associated with methionine metabolism, which helps predict prognosis and response to treatment in BC. The function of APOC1 in regulating macrophage polarization was explored.

Resveratrol-driven macrophage polarization: unveiling mechanisms and therapeutic potential

Resveratrol, a polyphenolic compound known for its diverse biological activities, has demonstrated multiple pharmacological effects, including anti-inflammatory, anti-aging, anti-diabetic, anti-cancer, and cardiovascular protective properties. Recent studies suggest that these effects are partly mediated through the regulation of macrophage polarization, wherein macrophages differentiate into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Our review highlights how resveratrol modulates macrophage polarization through various signaling pathways to achieve therapeutic effects. For example, resveratrol can activate the senescence-associated secretory phenotype (SASP) pathway and inhibit the signal transducer and activator of transcription (STAT3) and sphingosine-1-phosphate (S1P)-YAP signaling axes, promoting M1 polarization or suppressing M2 polarization, thereby inhibiting tumor growth. Conversely, it can promote M2 polarization or suppress M1 polarization by inhibiting the NF-κB signaling pathway or activating the PI3K/Akt and AMP-activated protein kinase (AMPK) pathways, thus alleviating inflammatory responses. Notably, the effect of resveratrol on macrophage polarization is concentration-dependent; moderate concentrations tend to promote M1 polarization, while higher concentrations may favor M2 polarization. This concentration dependence offers new perspectives for clinical treatment but also underscores the necessity for precise dosage control when using resveratrol. In summary, resveratrol exhibits significant potential in regulating macrophage polarization and treating related diseases.