Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease with unclear causes and limited treatment options. Sodium butyrate (NaB), a byproduct of dietary fiber in the intestine, has demonstrated efficacy in treating inflammation. However, the precise anti-inflammatory mechanisms of NaB in colon inflammation remain largely unexplored. This study aims to investigate the effects of NaB on dextran sulfate sodium (DSS)-induced colitis in rats. The findings indicate that oral administration of NaB effectively prevent colitis and reduce levels of serum or colon inflammatory factors. Additionally, NaB demonstrated in vitro inhibition of RAW264.7 inflammation cytokines induced by LPS, along with suppression of the ERK and NF-κB signaling pathway activation. Moreover, NaB mitigated LPS and Nigericin-induced RAW264.7 pyroptosis by reducing indicators of mitochondrial damage, including increased mitochondrial membrane potential (JC-1) levels and decreased Mito-ROS production. NaB increases ZO-1 and Occludin expression in CaCo2 cells by inhibiting RAW264.7 pyroptosis. These results suggest that NaB could be utilized as a therapeutic agent or dietary supplement to alleviate colitis.

Background: In recent years, the incidence of Crohn's disease (CD) has shown a significant global increase, with numerous studies demonstrating its correlation with various cancers. This study aims to identify novel biomarkers for diagnosing CD and explore their potential applications in pan-cancer analysis. Methods: Gene expression profiles were retrieved from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified using the "limma" R package. Key biomarkers were selected through an integrative machine learning pipeline combining LASSO regression, neural network modeling, and Support Vector Machine-Recursive Feature Elimination (SVM-RFE). Six hub genes were identified and further validated using the independent dataset GSE169568. To assess the broader relevance of these biomarkers, a standardized pan-cancer dataset from the UCSC database was analyzed to evaluate their associations with 33 cancer types. Results: Among the identified biomarkers, S100 calcium binding protein P (S100P) and S100 calcium binding protein A8 (S100A8) emerged as key candidates for CD diagnosis, with strong validation in the independent dataset. Notably, S100P displayed significant associations with immune cell infiltration and patient survival outcomes in both liver and lung cancers. These findings suggest that chronic inflammation and immune imbalances in CD may not only contribute to disease progression but also elevate cancer risk. As an inflammation-associated biomarker, S100P holds particular promise for both CD diagnosis and potential cancer risk stratification, especially in liver and lung cancers. Conclusion: Our study highlights S100P and S100A8 as potential diagnostic biomarkers for CD. Moreover, the pan-cancer analysis underscores the broader clinical relevance of S100P, offering new insights into its role in immune modulation and cancer prognosis. These findings provide a valuable foundation for future research into the shared molecular pathways linking chronic inflammatory diseases and cancer development.

The innate immune system's inactivation and microbial biofilm-induced antibiotic resistance are the main causes of implant-associated infections (IAIs), which frequently result in implant surgical failure. Refractory recolonization is the consequence of standard therapies that are unable to consistently suppress escaping planktonic bacteria from biofilm, thereby enabling IAIs to thrive. Here, we specifically designed a macrophage-like biomimetic nanoparticle (F/R@PM) for a biofilm microenvironment (BME), which was fabricated by coating the cell membrane derived from macrophage onto poly (lactic-co-glycolic acid) (PLGA) namoparticles (NPs) loaded with FOT (NO donor) and R837 (TLR7 agonist). After injecting F/R@PM into mice with implant-associated infections, it was able to selectively target macrophages through macrophage membrane proteins on its surface and effectively release FOT and R837. Then, FOT that spreads outside the cell could react with glutathione (GSH) in the BEM to rapidly produce a large amount of NO inside biofilms to destroy the biofilm and kill bacteria. At the same time, R837 would encourage macrophages to scavenge planktonic bacteria that had escaped biofilm disintegration through improved phagocytosis. Overall, this work shows that NO treatment and immunotherapy together have promising potential for the long-term and efficient control and eradication of IAIs.

Psoriasis is a chronic inflammatory skin condition driven by immune system dysfunction, genetic predisposition and environmental factors. Patients with psoriasis experience a well-known clinical phenomenon of 'winter severity and summer relief', in which seasonal environmental factors play critical roles in the onset and progression of psoriasis. These factors include temperature, humidity, infection, light exposure and psychological stress. Seasonal changes in temperature and humidity can compromise skin barrier function and exacerbate inflammatory responses, thereby worsening psoriasis symptoms. Notably, during the winter, decreased light exposure leads to reduced vitamin D (VD) levels, reaching their lowest levels from late winter to early spring. This decline in VD levels is associated with increased disease activity, greater disease severity and more frequent flare-ups in patients with psoriasis. During the winter, influenza and Streptococcus pneumoniae infections are more prevalent, which can further exacerbate psoriasis symptoms. Moreover, the environmental conditions in winter can trigger or intensify feelings of depression, which may adversely affect psoriasis through the brain-skin axis. In this comprehensive review, we thoroughly examined the influence of seasonal environmental factors on the incidence, recurrence and severity of psoriasis. By clarifying these complex relationships, we aimed to support the future development of more personalised and effective treatment and management strategies for patients with psoriasis.

Following the COVID-19 pandemic, there are many chronically ill Long COVID (LC) patients with different symptoms of varying degrees of severity. The pathological pathways of LC remain unclear until recently and make identification of path mechanisms and exploration of therapeutic options an urgent challenge. There is an apparent relationship between LC symptoms and impaired cholinergic neurotransmission.

This paper reviews the current literature on the effects of blocked nicotinic acetylcholine receptors (nAChRs) on the main affected organ and cell systems and contrasts this with the unblocking effects of the alkaloid nicotine. In addition, mechanisms are presented that could explain the previously unexplained phenomenon of post-vaccination syndrome (PVS). The fact that not only SARS-CoV-2 but numerous other viruses can bind to nAChRs is discussed under the assumption that numerous other post-viral diseases and autoimmune diseases (ADs) may also be due to impaired cholinergic transmission. We also present a case report that demonstrates changes in cholinergic transmission, specifically, the availability of α4β2 nAChRs by using (-)-[18F]Flubatine whole-body positron emission tomography (PET) imaging of cholinergic dysfunction in a LC patient along with a significant neurological improvement before and after low-dose transcutaneous nicotine (LDTN) administration. Lastly, a descriptive analysis and evaluation were conducted on the results of a survey involving 231 users of LDTN.

A substantial body of research has emerged that offers a compelling explanation for the phenomenon of LC, suggesting that it can be plausibly explained because of impaired nAChR function in the human body. Following a ten-day course of transcutaneous nicotine administration, no enduring neuropathological manifestations were observed in the patient. This observation was accompanied by a significant increase in the number of free ligand binding sites (LBS) of nAChRs, as determined by (-)-[18F]Flubatine PET imaging. The analysis of the survey shows that the majority of patients (73.5%) report a significant improvement in the symptoms of their LC/MEF/CFS disease as a result of LDTN.

In conclusion, based on current knowledge, LDTN appears to be a promising and safe procedure to relieve LC symptoms with no expected long-term harm.

Diabetic Foot Ulcers (DFUs) are chronic foot wounds, in a person with diabetes, which are associated with peripheral arterial insufficiency and/or peripheral neuropathy of the lower limb. Recent UK audit figures report that approximately 50-60 % of DFUs remain unhealed after 12 weeks. Previous research has suggested that ischaemia plays a key role in the pathophysiology of many chronic wounds, including DFUs. For this reason, hyperbaric oxygen therapy (HOT) has been investigated. The study aimed to investigate 1) Current understanding of the physiology of normal wound healing and the pathological mechanisms that occur in DFUs to interrupt these processes; 2) Effectiveness of current DFU treatment approaches; 3) Effectiveness from clinical trials and meta-analyses for any demonstrated therapeutic benefits of HOT in the treatment of DFUs, 4) Patient selection criteria for HOT, and patients who stand to benefit most from treatment. The review found that wound healing is a complex process, involving many cells and signalling molecules, and it remains incompletely understood. However, current evidence suggests that hyperglycaemia, hypoxia, chronic inflammation (due to infection, immune-cell dysfunction or other causes), peripheral neuropathy, and macro- and micro-vascular dysfunction may all adversely affect DFU healing. The review found that current NICE guidelines do not approve HOT therapy in the UK for DFU's, despite encouraging clinical research findings. HOT shows theoretical promise and has been successfully used in the treatment of individual DFUs for several decades. Despite this, there remains a lack of strong clinical evidence of benefits to encourage HOT's wider use. The review found that there were four important patient selection criteria for HOT treatment, including glycaemic control, possible contraindications and complications associated with treatment, ulcer severity and resistance to first and second line treatments. The review concluded that further high-quality clinical research is needed to improve the evidence base.

The mechanisms by which neutrophils acquire pro-tumor properties remain poorly understood. In pancreatic cancer, cancer-associated fibroblasts (CAFs) may interact with neutrophils, directing them to promote tumor progression.

To validate the association between CAFs and neutrophils, the localization of neutrophils was examined in clinically resected pancreatic cancer specimens. CAFs were produced by culturing in cancer-conditioned media, and the effects of these CAFs on neutrophils were examined. In vitro migration and invasion assays assess the effect of CAF-activated neutrophils on cancer cells. The factors secreted by the activated neutrophils were also explored. Finally, pirfenidone (PFD) was tested to determine whether it could suppress the pro-tumor functions of activated neutrophils.

In pancreatic cancer specimens, neutrophils tended to co-localize with IL-6-positive CAFs. Neutrophils co-cultured with CAFs increased migratory capacity and prolonged life span. CAF-affected neutrophils enhance the migratory and invasive activities of pancreatic cancer cells. IL-8 is the most upregulated cytokine secreted by the neutrophils. PFD suppresses IL-8 secretion from CAF-stimulated neutrophils and mitigates the malignant traits of pancreatic cancer cells.

CAFs activate neutrophils and enhance the malignant phenotype of pancreatic cancer. The interactions between cancer cells, CAFs, and neutrophils can be disrupted by PFD, highlighting a potential therapeutic approach.

Amino acids are pivotal regulators of immune cell metabolism, signaling pathways, and gene expression. In myeloid cells, these processes underlie their functional plasticity, enabling shifts between pro-inflammatory, anti-inflammatory, pro-tumor, and anti-tumor activities. Within the tumor microenvironment, amino acid metabolism plays a crucial role in mediating the immunosuppressive functions of myeloid cells, contributing to tumor progression. This review delves into the mechanisms by which specific amino acids-glutamine, serine, arginine, and tryptophan-regulate myeloid cell function and polarization. Furthermore, we explore the therapeutic potential of targeting amino acid metabolism to enhance anti-tumor immunity, offering insights into novel strategies for cancer treatment.

Cigarette smoking is known to affect muscle function and exercise capacity, including muscle fatigue resistance. Most studies showed diminished cross-sectional area and fibre type shifting in slow-twitch muscles such as the soleus, while effects on fast-twitch muscles were seldom reported and the differential responses between muscle types in response to exposure to cigarette smoke (CS) were largely unknown. This study aimed to elucidate the histomorphological, biochemical and transcriptomic changes induced by CS on both slow-twitch and fast-twitch muscles.

Male Sprague-Dawley rats were randomly divided into two groups: sham air (SA) and CS. The rats were exposed to CS for 8 weeks using an exposure chamber system to mimic smoking conditions. Histomorphological analyses on muscle fibre type and cross-sectional area were determined in soleus and extensor digitorum longus (EDL). Transcriptomic profiles were investigated for identifying differentially expressed genes (DEGs) and potential mechanistic pathways involved. Inflammatory responses in terms of the macrophage population and the level of inflammatory cytokines were measured. Markers for muscle-specific proteolysis were also examined.

Soleus muscle, but not in EDL, exhibited a significant increase in Type IIa fibres (SA: 9.0 ± 3.3%; CS: 19.8 ± 2.4%, p = 0.002) and decrease in Type I fibres (SA: 90.1 ± 3.6%; CS: 77.9 ± 3.3%, p = 0.003) after CS exposure. RNA sequencing revealed 165 identified DEGs in soleus including upregulation of 'Cd68', 'Ccl2' and 'Ucp2' as well as downregulation of 'Ucp3', etc. Pathways enrichment analysis revealed that the upregulated pathways in soleus were related to immune system and cellular response, while the downregulated pathways were related to oxidative metabolism. Only 10 DEGs were identified in EDL with less enriched pathways. The soleus also showed elevated pro-inflammatory cytokines, and the total macrophage marker CD68 was significantly higher in soleus of CS compared to the SA group (CD68+/no. of fibre: SA = 60.3 ± 39.3%; CS = 106.5 ± 27.2%, p = 0.0039), while the two groups in EDL muscle showed no significant difference. The expression of E3 ubiquitin ligase atrogin-1 associated with muscle degradation pathways was 1.63-fold higher in the soleus after CS, while no significant differences were observed in the EDL.

The CS-induced inflammatory responses on soleus muscle are likely mediated via targeting mitochondrial-related signalling, resulting in mitochondrial dysfunction and impaired oxidative capacity. The presumably less active mitochondrial-related signalling in EDL renders it less susceptible to changes towards CS, accounting for differential impacts between muscle types.

The Cissus gongylodes has traditionally been used in the diet of indigenous people in Brazil and in traditional medicine for kidney stone removal and inflammatory diseases. The active compounds responsible for these pharmacological activities are unknown.

This study aims to isolate, for the first time, the compounds in the decoction of C. gongylodes leaves responsible for their anti-inflammatory and anti-urolithiatic ethnopharmacological properties.

The most active fractions of the C. gongylodes leaf decoction were fractionated using SPE-C18 and the compounds were purified through HPLC-UV-DAD. The decoction fractions and isolated compounds were evaluated for their anti-inflammatory and anti-urolithiatic activities. The anti-inflammatory activity was assessed using an ex vivo assay in human blood induced by LPS and calcium ionophore, measuring inflammatory mediators, PGE2 and LTB4. The anti-urolithiatic activity was evaluated using an in vitro experimental model with human urine to determine the dissolution of the most recurrent calcium oxalate (CaOx) crystals. Additionally, the decoction was chemically characterized through metabolomic analysis using UHPLC-ESI-HRMS.

The isolated compounds from the decoction of C. gongylodes, including rutin, eriodictyol 3'-O-glycoside, and isoquercetin, have demonstrated significant multi-target actions. These components act as anti-inflammatory agents by inhibiting the release of main inflammatory mediators, PGE2 and LTB4. Additionally, they exhibit anti-urolithiatic properties, promoting the dissolution of calcium oxalate (CaOx) crystals. Furthermore, the characterization of the decoction by UHPLC-ESI-HRMS revealed a high content of flavonoids, mainly glycosylated flavonoids.

The results support the traditional use of C. gongylodes decoction, identifying the compounds responsible for its anti-inflammatory and anti-urolithiatic effects. The decoction fractions and isolated compounds exhibited dual anti-inflammatory activity, effectively inhibiting key inflammatory pathways and potentially presenting fewer adverse effects while also promoting the dissolution of CaOx crystals associated with urolithiasis. The multi-target action displayed by C. gongylodes is particularly desirable in the treatment of urolithiasis, as inflammation and PGE2 production precede and contribute to the formation of CaOx crystals in the kidneys. Based on these actions, C. gongylodes emerges as a potent source of active compounds for the development of new treatments for urolithiasis.

Paxillin and kindlin are essential regulatory proteins involved in cell adhesion, migration, and signal transduction. Paxillin influences cytoskeletal dynamics by interacting with multiple signaling proteins, while kindlin regulates integrin activation, affecting adhesion and motility. This review examines the structures and functions of these proteins, focusing on their roles in cancer progression, immune response, and therapeutic potential. The cooperation between paxillin and kindlin in integrin activation and focal adhesion dynamics offers valuable insights into tumor metastasis, immune function, and tissue repair.

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.

Upon stimulation and activation, mast cells (MCs) release soluble mediators, including histamine, proteases, and cytokines. These mediators are often stored within cytoplasmic granules in MCs and may be released in a granulated form. The secretion of cytokines and chemokines occurs within hours following activation, with the potential to result in chronic inflammation. In addition to their role in allergic inflammation, MCs are components of the tumor microenvironment (TME). MicroRNAs (miRNAs) are small RNA molecules that do not encode proteins, but regulate post-transcriptional gene expression by binding to the 3' non-coding regions of mRNAs. This plays a crucial role in the function of MC, including the key processes of MC proliferation, maturation, apoptosis, and activation. It has been demonstrated that miRNAs are also present in extracellular vesicles (EVs) secreted by MCs. EVs derived from MCs mediate intercellular communication by carrying miRNAs, affecting various diseases including allergic diseases, intestinal disorders, neuroinflammation, and tumors. These findings provide important insights into the therapeutic mechanisms and targets of miRNAs in MCs that affect diseases. This review discusses the relevance of miRNA production by MCs in regulating their own activity and the effect of miRNAs putatively produced by other cells in the control of MC activity and their participation in selected pathologies.

Chitosan, a biodegradable and biocompatible natural polymer composed of β-(1-4)-linked N-acetyl glucosamine (GlcNAc) and d-glucosamine (GlcN) and derived from crustacean shells, has been widely studied for various biomedical applications, including drug delivery, cartilage repair, wound healing, and tissue engineering, because of its unique physicochemical properties. One of the most promising areas of research is the investigation of the immunomodulatory properties of chitosan, since the biopolymer has been shown to modulate the maturation, activation, cytokine production, and polarization of dendritic cells and macrophages, two key immune cells involved in the initiation and regulation of innate and adaptive immune responses, leading to enhanced immune responses. Several signaling pathways, including the cGAS-STING, STAT-1, and NLRP3 inflammasomes, are involved in chitosan-induced immunomodulation. This review provides a comprehensive overview of the current understanding of the in vitro immunomodulatory effects of chitosan. This information may facilitate the development of chitosan-based therapies and vaccine adjuvants for various immune-related diseases.

Cervical cancer (CESC) presents significant clinical challenges due to its complex tumor microenvironment (TME) and varied treatment responses. This study identified undifferentiated M0 macrophages as high-risk immune cells critically involved in CESC progression. Co-culture experiments further demonstrated that M0 macrophages significantly promoted HeLa cell proliferation, migration, and invasion, underscoring their pivotal role in modulating tumor cell behavior within the TME. A nine-gene prognostic model constructed from immune gene signatures highlighted CXCL8 as a key regulator of M0 macrophage behavior. Functional experiments demonstrated that CXCL8 knockdown in M0 macrophages inhibited their proliferation, shifted polarization toward an M1-dominant phenotype, and reduced tumor-promoting M2 polarization. Co-culture experiments with CXCL8-deficient M0 macrophages further revealed a suppression of HeLa cell proliferation, migration, and invasion. These findings position M0 macrophages as central regulators within the TME and suggest that targeting pathways like CXCL8 could provide novel therapeutic strategies for improving outcomes in CESC patients.

Rationale: The mannose receptor (CD206, expressed by the gene Mrc1) is a surface marker overexpressed by anti-inflammatory and pro-tumoral macrophages. As such, CD206+ macrophages play key roles in the immune response to different pathophysiological conditions and represent a promising diagnostic and therapeutic target. However, methods to specifically target these cells remain challenging. In this study, we describe a multi-mannose approach to develop CD206-targeting fluorescent and MRI agents that specifically and sensitively detect and monitor CD206+ macrophage immune response in different disease conditions. Methods: We designed and synthesized fluorescent agents MR1-cy5 and MR2-cy5, and MRI agents Mann2-DTPA-Gd and MannGdFish. Cellular assays using pro-inflammatory and anti-inflammatory macrophages differentiated from RAW 264.7 cells were performed, and signals were detected by fluorescence microscopy and inductively coupled plasma mass spectrometry (ICP-MS) to validate specificity in vitro. In vivo specificity and efficacy of the agents were evaluated by MRI in a subcutaneous wound healing model and experimental glioma with Mrc1 +/+ without and with D-mannose treatment, Mrc1 +/-, and Mrc1 -/- mice, and in stroke. One-way ANOVA and two-way ANOVA tests were used for data analysis. P < 0.05 was considered statistically different. Results: Both in vitro fluorescence imaging with MR2-cy5, ICP-MS with Mann2-DTPA-Gd, and in vivo MRI in Mrc1 -/- mice confirmed the specificity of our approach. Mann2-DTPA-Gd MRI can track the changes of CD206+ macrophages at different stages of wound healing, correlating well with flow cytometry data using another anti-inflammatory macrophage marker (arginase-1). The specificity and efficacy of Mann2-DPTA-Gd were further validated in experimental glioma, in which Mann2-DTPA-Gd imaging detected CD206+ tumor-associated macrophages (TAMs), demonstrated significantly decreased signals in Mrc1 +/- mice and Mrc1 -/- mice, and tracked treatment changes in D-mannose-treated Mrc1 +/+ mice. Furthermore, Mann2-DTPA-Gd can report microglia/macrophages and correlate with histology in stroke. The more Gd-stable agent MannGdFish demonstrated similar efficacy as Mann2-DTPA-Gd in vivo with favorable biodistribution and pharmacokinetics. Conclusion: We have developed a fluorescent agent (MR2-cy5) and MRI agents (Mann2-DTPA-Gd and MannGdFish) with two mannose moieties that are highly specific to CD206 and can track CD206+ macrophages in disease models of wound healing, tumor, and neurological disease. Importantly, MannGdFish, with its high specificity, stability, favorable biodistribution, and pharmacokinetics, is a promising translational candidate to noninvasively monitor CD206+ macrophages in repair/regeneration and tumors in patients. In addition, with the specific binding motif to CD206, other imaging modalities and therapeutic agents could also be introduced for theranostic applications.

The formation of neutrophil extracellular traps (NETs) is known as an important part of the innate immune response. Still, some mechanisms regarding their formation and role during a disease are not completely understood yet. To visualize NETs by immunofluorescence microscopy, a chemical fixation is required. Therefore, this study focused on the effect of chemical fixatives on immunofluorescence staining of selected neutrophil and NET-markers, including myeloperoxidase (MPO), DNA/histone-1-complexes and citrullinated histone H3 (H3cit). Neutrophils isolated from fresh human blood were stimulated with phorbol-12-myristate 13-acetate (PMA) to induce NETs and fixed with paraformaldehyde (PFA, 4%), glutardialdehyde (GA, 5%) or methanol (MeOH, 100%) using different incubation times depending on the used fixative. We found that different fixation times with PFA had no effect on the staining intensity of MPO or DNA/histone-1-complex antibodies. For the staining of H3cit, fixation with PFA for 24 h decreased the signal intensity whereas 30 min fixation time had no effect. In contrast, glutardialdehyde induced a high amount of autofluorescence, and the fixation with 100% MeOH resulted in visible cellular damage. Therefore, we recommend 15-30 min PFA fixation for the respective stainings. Our results provide a solid basis for future experiments to study neutrophil activation and NET-formation.

Neutrophils are the most abundant cell type in human blood and play a crucial role in the immune system and development of tumors. This review begins with the generation and development of neutrophils, traces their release from the bone marrow into the bloodstream, and finally discusses their role in the hepatocellular carcinoma (HCC) microenvironment. It elaborates in detail the mechanisms by which tumor-associated neutrophils (TANs) exert antitumor or protumor effects under the influence of various mediators in the tumor microenvironment. Neutrophils can exert antitumor effects through direct cytotoxic action. However, they can also accelerate the formation and progression of HCC by being recruited and infiltrated, promoting tumor angiogenesis, and maintaining an immunosuppressive microenvironment. Therefore, based on the heterogeneity and plasticity of neutrophils in tumor development, this review summarizes the current immunotherapies targeting TANs, discusses potential opportunities and challenges, and provides new insights into exploring more promising strategies for treating HCC.

The view of neutrophils has shifted from simple phagocytic cells, whose main function is to kill pathogens, to very complex cells that are also involved in immune regulation and tissue repair. These cells are essential for maintaining and regaining tissue homeostasis. Neutrophils can be viewed as double-edged swords in a range of situations. The potent killing machinery necessary for immune responses to pathogens can easily lead to collateral damage to host tissues when inappropriately controlled. Furthermore, some subtypes of neutrophils are potent pathogen killers, whereas others are immunosuppressive or can aid in tissue healing. Finally, in tumor immunology, many examples of both protumorigenic and antitumorigenic properties of neutrophils have been described. This has important consequences for cancer therapy, as targeting neutrophils can lead to either suppressed or stimulated antitumor responses. This review will discuss the current knowledge regarding the pro- and antitumorigenic roles of neutrophils, leading to the concept of a confused state of neutrophil-driven pro-/antitumor responses.

Osteoarthritis (OA) is a prevalent joint disease worldwide that significantly impacts the quality of life of individuals, particularly those in middle-aged and elderly populations. OA was initially considered as non-inflammatory arthritis, but recent studies have identified a substantial number of immune responses in OA, leading to the recognition of inflammation as a key factor in its pathogenesis. An increasing number of studies have found that mast cell (MC) and MC-secreted inflammatory mediators and cytokines are notably increased in the synovial fluid of OA patients, indicating a potential association between MCs and the onset and progression of synovial inflammation. The present review aims to summarize the significance and mechanism of MCs in the pathogenesis of OA. Meanwhile, we also discuss the clinical potential of using MCs as therapeutic target for OA therapy. Modulating the activities of MCs or the mediators of MCs in the synovial fluid inflammatory microenvironment will be promising new options for the treatment of OA.

Neutrophils are essential components of the innate immune system that defend against the invading pathogens, such as bacteria, viruses, and fungi, as well as having regulatory roles in various conditions, including tissue repair, cancer immunity, and inflammation modulation. The function of neutrophils is strongly related to their mode of cell death, as different types of cell death involve various cellular and molecular alterations. Apoptosis, a non-inflammatory and programmed type of cell death, is the most common in neutrophils, while other modes of cell death, including NETOsis, necrosis, necroptosis, autophagy, pyroptosis, and ferroptosis, have specific roles in neutrophil function regulation. Immunometabolism refers to energy and substance metabolism in immune cells, and profoundly influences immune cell fate and immune system function. Intercellular and intracellular signal transduction modulate neutrophil metabolism, which can, in turn, alter their activities by influencing various cell signaling pathways. In this review, we compile an extensive body of evidence demonstrating the role of neutrophil metabolism in their various forms of cell death. The review highlights the intricate metabolic characteristics of neutrophils and their interplay with various types of cell death.

Gram-negative bacteria infections in diabetic wounds are complicated to control, leading to amputation and even death in severe cases. There is an urgent need to develop effective therapeutic strategies. In recent years, electrospinning has attracted much attention due to its resemblance to extracellular matrix (ECM), which can regulate local cellular proliferation, migration, differentiation, etc.; however, its use is limited by its high cost and difficulty in transportation. This study proposes a portable direct-injection porous fibre scaffold containing polymyxin B (PMB) for local slow release for treating diabetic wounds infected with difficult-to-heal Gram-negative bacteria. The handheld portable electrospinner is lightweight and easy to operate and can be directly sprayed in situ to cover wounds with irregular shapes and sizes. When covering the wound in situ, the PVB/PVP nanofiber membrane can protect it from the external environment. Meanwhile, the nanofiber membrane dressing has a porosity of 20 % and a controlled drug-loading capacity. What's more, the evaluation of a whole skin defect model of type II diabetes mellitus infected with Gram-negative bacteria showed that the PMB-loaded nanofiber membrane could effectively inhibit Gram-negative bacteria infection, promote collagen deposition and re-epithelialization, and regulate the polarization of M1-type macrophages to M2-type macrophages, thereby controlling inflammation and promoting vascular regeneration, and significantly accelerating the healing of diabetic wounds. Overall, portable direct-injection porous fibre scaffold-loaded drugs are essential for healing difficult-to-heal wounds as local slow-release drug delivery.

In recent years, with the advance of research, the role of tumor-associated neutrophils (TANs) in tumors has become a research hotspot. As important effector cells in the innate immune system, neutrophils play a key role in the immune and inflammatory responses of the body. As the first line of defense against bacterial and fungal infections, neutrophils have the ability to kill invading pathogens. In the pathological state of malignant tumors, the phenotype of neutrophils is altered and has an important regulatory function in tumor development. The C-X-C motif chemokine receptor 2(CXCR2) is a key molecule that mediates the migration and aggregation signaling pathway of immune cells, especially neutrophils. This review focuses on the regulation of CXCR2 on TANs in the process of tumorigenesis and development, and emphasizes the application significance of CXCR2 inhibitors in blocking the migration of TANs to tumors.

The present work is designed to explore the anti-inflammatory properties of AA and its modulatory effects on celecoxib (CEL) and ketoprofen (KET) through in vitro, ex vivo, in vivo, and in silico approaches. Different concentrations of AA were utilized to evaluate the membrane-stabilizing potential via egg albumin and the Human Red Blood Cell (HRBC) denaturation model. In the animal model, formalin (50 μL) was injected into the right hind paw of young chicks to induce inflammation. AA was administered at 20 and 40 mg/kg (p.o.) to the experimental animals. We used CEL and KET as positive controls. The vehicle was provided as a control group. Two combinations of AA with CEL and KET were also investigated in all tests to assess the modulatory activity of AA. In addition, in silico investigation was used for predictions about drug-likeness, pharmacokinetics, and toxicity of the selected chemical compounds, and the study also evaluated the binding affinity, visualization, and stability of ligand-receptor interactions through molecular dynamic (MD) simulation. Results manifested that AA concentration-dependently significantly inhibited the egg albumin denaturation (IC50: 27.53 ± 0.88 μg/ml) and breakdown of HRBC (IC50: 15.69 ± 0.75 μg/ml), indicating the membrane stabilizing potential compared to the control group. AA also significantly (p < 0.05) lessened the frequency of licking and alleviated the paw edema in a dose-dependent manner in an in vivo test. However, AA reduced the activity of CEL and KET in combination treatment. AA showed good pharmacokinetic characteristics to be considered as a therapeutic candidate. Additionally, the in silico study displayed that AA demonstrated a relatively higher docking score of -9.1 kcal/mol with the cyclooxygenase-2 (COX-2) enzyme and stable binding in MD simulation. Whereas the standard ligand (CEL) expressed the highest binding value of -9.2 kcal/mol to the COX-2.

Lithospermum erythrorhizon (LE), a medicinal plant from the Boraginaceae family, is traditionally used in East Asia for its therapeutic effects on skin conditions, including infections, inflammation, and wounds. Recently, the role of extracellular vesicles (EVs) as mediators of intercellular communication that regulate inflammation and promote tissue regeneration has garnered increasing attention in the field of regenerative medicine. This study investigates exosome-like vesicles derived from LE callus (LELVs) and their potential in enhancing wound healing. In vitro studies using normal human dermal fibroblasts (NHDFs) demonstrated that LELVs significantly improved cell viability, proliferation, and wound closure, while also enhancing collagen type I synthesis, indicating anti-inflammatory and regenerative properties. For in vivo analysis, LELVs were applied to lipopolysaccharide (LPS)-induced wounds in mice, where wound healing progression was monitored over 14 days. LELV-treated wounds exhibited accelerated re-epithelialization, reduced inflammation, and improved tissue remodeling, with histological analysis revealing enhanced collagen deposition and reduced inflammatory cell infiltration. These results highlight the ability of LELVs to modulate the inflammatory response and promote wound healing. With their natural origin, low immunogenicity, and ease of production, LELVs represent a promising alternative to synthetic treatments for inflammation-associated skin injuries and hold significant potential for clinical applications in wound care.

Numerous viruses that propagate through the respiratory tract may be initially engulfed by macrophages (Mφs) within the alveoli, where they complete their first replication cycle and subsequently infect the adjacent epithelial cells. This process can lead to significant pathological damage to tissues and organs, leading to various diseases. As essential components in host antiviral immune systems, Mφs can be polarized into pro-inflammatory M1 Mφs or anti-inflammatory M2 Mφs, a process involving multiple signaling pathways and molecular mechanisms that yield diverse phenotypic and functional features in response to various stimuli. In general, when infected by a virus, M1 macrophages secrete pro-inflammatory cytokines to play an antiviral role, while M2 macrophages play an anti-inflammatory role to promote the replication of the virus. However, recent studies have shown that some viruses may exhibit the opposite trend. Viruses have evolved various strategies to disrupt Mφ polarization for efficient replication and transmission. Notably, various factors, such as mechanical softness, the altered pH value of the endolysosomal system, and the homeostasis between M1/M2 Mφs populations, contribute to crucial events in the viral replication cycle. Here, we summarize the regulation of Mφ polarization, virus-induced alterations in Mφ polarization, and the antiviral mechanisms associated with these changes. Collectively, this review provides insights into recent advances regarding Mφ polarization in host antiviral immune responses, which will contribute to the development of precise prevention strategies as well as management approaches to disease incidence and transmission.

Radionuclide-contaminated wounds face clinical dilemmas such as repeated erosion and ulceration and are difficult to heal. In this work, we aimed to develop a biodegradable hydrogel with a beneficial effect on radionuclide-contaminated wounds and initially investigated the mechanism of action of the hydrogel. The hydrogel was produced through the ring-opening polymerization of polycaprolactone (PCL) triggered by polyethylene glycol (PEG), and its physicochemical properties were characterized by gel permeation chromatography, nuclear magnetic resonance, rheological properties testing, and other techniques. The low critical solution temperatures were 30 °C and 46 °C, which are suitable for the human body to realize the degradable properties of the hydrogel. A radionuclide-contaminated wound model was established, which proved that the biodegradable hydrogel had good healing properties and did not form secondary lesions. The effect was better than clinically used EGF or VB12. Pathological results showed that mature granulation tissue formed on the 7th day after the injury, and by the 10th day after the injury, the scab had completely fallen off, the epithelial coverage had reached over 70% and the wound was essentially completely healed. Additionally, the hydrogel affects immune metabolism, regulates immune cell function, promotes the formation of new blood vessels and granular tissue, and effectively accelerates the healing process of radionuclide-contaminated wounds.

HCC, the most common type of primary liver cancer, is a leading cause of cancer-related mortality worldwide. Although the advancement of immunotherapies by immune checkpoint inhibitors (ICIs) that target programmed cell death 1 or programmed cell death 1-ligand 1 has revolutionized the treatment for HCC, the majority is still not beneficial. Accumulating evidence has pointed out that the potent immunosuppressive tumor microenvironment in HCC poses a great challenge to ICI therapeutic efficacy. As a key component in tumor microenvironment, tumor-associated macrophages (TAMs) play vital roles in HCC development, progression, and ICI low responsiveness. Mechanistically, TAM can promote cancer invasion and metastasis, angiogenesis, epithelial-mesenchymal transition, maintenance of stemness, and most importantly, immunosuppression. Targeting TAMs, therefore, represents an opportunity to enhance the ICI therapeutic efficacy in patients with HCC. While previous research has primarily focused on biochemical cues influencing macrophages, emerging evidence highlights the critical role of biophysical signals, such as substrate stiffness, topography, and external forces. In this review, we summarize the influence of biophysical characteristics within the tumor microenvironment that regulate the phenotype and function of TAMs in HCC pathogenesis and progression. We also explore the possible mechanisms and discuss the potential of manipulating biophysical cues in regulating TAM for HCC therapy. By gaining a deeper understanding of how macrophages sense and respond to mechanical forces, we may potentially usher in a path toward a curative approach for combinatory cancer immunotherapies.

Silicone mammary implants (SMIs) frequently result in capsular fibrosis, which is marked by the overproduction of fibrous tissue surrounding the implant. This review provides a detailed examination of the molecular and immunological mechanisms driving capsular fibrosis, focusing on the role of foreign body responses (FBRs) and microbial biofilm formation. We investigate how microbial adhesion to implant surfaces and biofilm development contribute to persistent inflammation and fibrotic responses. The review critically evaluates antimicrobial strategies, including preoperative antiseptic protocols and antimicrobial-impregnated materials, designed to mitigate infection and biofilm-related complications. Additionally, advancements in material science, such as surface modifications and antibiotic-impregnated meshes, are discussed for their potential to reduce capsular fibrosis and prevent contracture of the capsule. By integrating molecular insights with clinical applications, this review aims to elucidate the current understanding of SMI-related fibrotic responses and highlight knowledge gaps. The synthesis of these findings aims to guide future research directions of improved antimicrobial interventions and implant materials, ultimately advancing the management of capsular fibrosis and enhancing patient outcomes.

Cheonggukjang (CGJ) is a traditional food, made by the fermentation of beans, and it has different recipes for different regions in Korea. However, it has anti-inflammatory, anti-cancer, and anti-obesity effects, and is known to affect changes in the intestinal microbiota. In this study, we investigated the immune-enhancing effects of four type CGJs (one commercial and three transitional CGJs). In the cyclophosphamide (CP)-treated immunosuppressed rat, oral administration of CGJs for 4 weeks was used to investigate weight of body and immune organ, change of microbiota, blood and serum parameters, inflammation pathways (MAPKs and NFκB) and histology of spleen. It showed an immunity-enhancing effect through increase Bacteroidetes in gut, the recovery of complete blood count, levels of cytokines and IgG, activation of inflammatory pathways, and histology of spleen. In conclusion, these results show that the intake of a commercial brand CGJ, and traditional CGJs can maintain or promote the body's immunity.

The kidney is an essential excretory organ that works as a filter of toxins and metabolic by-products of the human body and maintains osmotic pressure throughout life. The kidney undergoes several physiological, morphological, and structural changes with age. As life expectancy in humans increases, cell senescence in renal aging is a growing challenge. Identifying age-related kidney disorders and their cause is one of the contemporary public health challenges. While the structural abnormalities to the extracellular matrix (ECM) occur, in part, due to changes in MMPs, EMMPRIN, and Meprin-A, a variety of epigenetic modifiers, such as DNA methylation, histone alterations, changes in small non-coding RNA, and microRNA (miRNA) expressions are proven to play pivotal roles in renal pathology. An aged kidney is vulnerable to acute injury due to ischemia-reperfusion, toxic medications, altered matrix proteins, systemic hemodynamics, etc., non-coding RNA and miRNAs play an important role in renal homeostasis, and alterations of their expressions can be considered as a good marker for AKI. Other epigenetic changes, such as histone modifications and DNA methylation, are also evident in AKI pathophysiology. The endogenous production of gaseous molecule hydrogen sulfide (H2S) was documented in the early 1980s, but its ameliorative effects, especially on kidney injury, still need further research to understand its molecular mode of action in detail. H2S donors heal fibrotic kidney tissues, attenuate oxidative stress, apoptosis, inflammation, and GFR, and also modulate the renin-angiotensin-aldosterone system (RAAS). In this review, we discuss the complex pathophysiological interplay in AKI and its available treatments along with future perspectives. The basic role of H2S in the kidney has been summarized, and recent references and knowledge gaps are also addressed. Finally, the healing effects of H2S in AKI are described with special emphasis on epigenetic regulation and matrix remodeling.

The application of titanium (Ti) implants for patients with diabetes mellitus (DM) is still facing a significant challenge due to obstacles such as hyperglycemia, reactive oxygen species (ROS), and chronic inflammation, which hinders osseointegration. To address this issue, a Ti implant with dual functions of regulating polarization of macrophages and facilitating osseointergration is developed via hydrothermal reaction and hydrogel coating. The reactive oxygen species (ROS) and glucose (Glu) responsive hydrogel coating can locally deliver adenosine (ADO) in the early stage of implantation. The controlled release of ADO regulated the phenotype of macrophages, restored oxidative balance, and enhanced mitochondrial function during the early stages of implantation. Subsequently, strontium (Sr) ions will be released to promote osteogenic differentiation and proliferation of mesenchymal stem cells (MSCs), as the hydrogel coating degraded. It eventually leads to bone reconstruction during the late stages, aligning with the biological cascade of bone healing. The modified Ti implants showed effective osteogenesis for bone defects in DM patients, shedding light on the design and biological mechanisms of surface modification. This research offers promising potential for improving the treatment of bone-related complications in diabetic patients.

Developmental Endothelial Locus-1 (DEL-1), also known as EGF-like repeat and discoidin I-like domain-3 (EDIL3), is increasingly recognized for its multifaceted roles in immunoregulation and vascular biology. DEL-1 is a protein that is mainly produced by endothelial cells. It interacts with various integrins to regulate the behavior of immune cells, such as preventing unnecessary recruitment and inflammation. DEL-1 also helps in resolving inflammation by promoting efferocytosis, which is the process of clearing apoptotic cells. Its potential as a therapeutic target in immune-mediated blood disorders, cardiovascular diseases, and cancer metastasis has been spotlighted due to its wide-ranging implications in vascular integrity and pathology. However, there are still unanswered questions about DEL-1's precise functions and mechanisms. This review provides a comprehensive examination of DEL-1's activity across different vascular contexts and explores its potential clinical applications. It underscores the need for further research to resolve existing controversies and establish the therapeutic viability of DEL-1 modulation.

Hepatocellular carcinoma (HCC) is a highly frequent malignancy worldwide. The occurrence and progression of HCC is a complex process closely related to the polarization of tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). The polarization of TAMs is affected by a variety of signaling pathways and surrounding cells. Evidence has shown that TAMs play a crucial role in HCC, through its interaction with other immune cells in the TME. This review summarizes the origin and phenotypic polarization of TAMs, their potential impacts on HCC, and their mechanisms and potential targets for HCC immunotherapy.

Intestinal ischemia/reperfusion (I/R) injury is a serious condition that causes intestinal dysfunction and can be fatal. Previous research has shown that toll-like receptor 4 (TLR4) inhibitors have a protective effect against this injury. This study aimed to investigate the protective effects of TLR4 inhibitors, specifically cyclobenzaprine, ketotifen, amitriptyline, and naltrexone, in rats with intestinal (I/R) injury. Albino rats were divided into seven groups: vehicle control, sham-operated, I/R injury, I/R-cyclobenzaprine (10 mg/kg body weight), I/R-ketotifen (1 mg/kg body weight), I/R-amitriptyline (10 mg/kg body weight), and I/R-naltrexone (4 mg/kg body weight) groups. Anesthetized rats (urethane 1.8 g/kg) underwent 30 min of intestinal ischemia by occluding the superior mesenteric artery (SMA), followed by 2 h of reperfusion. Intestinal tissue samples were collected to measure various parameters, including malondialdehyde (MDA), nitric oxide synthase (NO), myeloperoxidase (MPO), superoxide dismutase (SOD), TLR4, intercellular adhesion molecule-1 (ICAM-1), nuclear factor kappa bp65 (NF-ĸBP65), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), macrophages CD68, myeloid differentiation factor 88 (MYD88), and toll interleukin receptor-domain-containing adaptor-inducing interferon β (TRIF). The use of TLR4 inhibitors significantly reduced MDA, MPO, and NO levels, while increasing SOD activity. Furthermore, it significantly decreased TLR4, ICAM-1, TNF-α, MCP-1, MYD88, and TRIF levels. These drugs also showed partial restoration of normal cellular structure with reduced inflammation. Additionally, there was a decrease in NF-ĸBP65 and macrophages CD68 staining compared to rats in the I/R groups. This study focuses on how TLR4 inhibitors enhance intestinal function and protect against intestinal (I/R) injury by influencing macrophages CD86 through (MYD88-TRIF) pathway, as well as their effects on oxidation and inflammation.

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by recurrent eczematous lesions and severe pruritus. The economic burden and time penalty caused by the relapse of AD reduce patients' life quality.

AD has complex pathogenesis, including genetic disorders, epidermal barrier dysfunction, abnormal immune responses, microbial dysbiosis of the skin, and environmental factors. Recently, the role of innate immune cells in AD has attracted considerable attention. This review highlighted recent findings on innate immune cells in the onset and progression of AD.

Innate immune cells play essential roles in the pathogenesis of AD and enough attention should be given for treating AD from the perspective of innate immunity in clinics.

Bacteria extracellular vesicles (BEVs), characterized as the lipid bilayer membrane-surrounded nanoparticles filled with molecular cargo from parent cells, play fundamental roles in the bacteria growth and pathogenesis, as well as facilitating essential interaction between bacteria and host systems. Notably, benefiting from their unique biological functions, BEVs hold great promise as novel nanopharmaceuticals for diverse biomedical potential, attracting significant interest from both industry and academia. Typically, BEVs are evaluated as promising drug delivery platforms, on account of their intrinsic cell-targeting capability, ease of versatile cargo engineering, and capability to penetrate physiological barriers. Moreover, attributing to considerable intrinsic immunogenicity, BEVs are able to interact with the host immune system to boost immunotherapy as the novel nanovaccine against a wide range of diseases. Towards these significant directions, in this review, we elucidate the nature of BEVs and their role in activating host immune response for a better understanding of BEV-based nanopharmaceuticals' development. Additionally, we also systematically summarize recent advances in BEVs for achieving the target delivery of genetic material, therapeutic agents, and functional materials. Furthermore, vaccination strategies using BEVs are carefully covered, illustrating their flexible therapeutic potential in combating bacterial infections, viral infections, and cancer. Finally, the current hurdles and further outlook of these BEV-based nanopharmaceuticals will also be provided.

During the foreign body response (FBR), macrophages fuse to form foreign body giant cells (FBGCs). Modulation of FBGC formation can prevent biomaterial degradation and loss of therapeutic efficacy. However, the microenvironmental cues that dictate FBGC formation are poorly understood with conflicting reports. Here, we identified molecular and cellular factors involved in driving FBGC formation in vitro. Macrophages demonstrated distinct fusion competencies dependent on monocyte differentiation. The transition from a proinflammatory to a reparative microenvironment, characterised by specific cytokine and growth factor programmes, accompanied FBGC formation. Toll-like receptor signalling licensed the formation of FBGCs containing more than 10 nuclei but was not essential for cell-cell fusion to occur. Moreover, the fibroblast-macrophage crosstalk influenced FBGC development, with the fibroblast secretome inducing macrophages to secrete more PDGF, which enhanced large FBGC formation. These findings advance our understanding as to how a specific and timely combination of cellular and microenvironmental factors is required for an effective FBR, with monocyte differentiation and fibroblasts being key players.

Pancreatic cancer (PC) is a highly malignant tumour of the digestive system with poor therapeutic response and low survival rates. Immunotherapy has rapidly developed in recent years and has achieved significant outcomes in numerous malignant neoplasms. However, responses to immunotherapy in PC are rare, and the immunosuppressive and desmoplastic tumour microenvironment (TME) significantly hinders their efficacy in PC. Tumour-associated neutrophils (TANs) play a crucial role in the PC microenvironment and exert a profound influence on PC immunotherapy by establishing a robust stromal shelter and restraining immune cells to assist PC cells in immune escape, which may subvert the current status of PC immunotherapy. The present review aims to offer a comprehensive summary of the latest progress in understanding the involvement of TANs in PC desmoplastic and immunosuppressive functions and to emphasise the potential therapeutic implications of focusing on TANs in the immunotherapy of this deleterious disease. Finally, we provide an outlook for the future use of TANs in PC immunotherapy.

Chronic rhinosinusitis (CRS) represents a heterogeneous disorder primarily characterized by the persistent inflammation of the nasal cavity and paranasal sinuses. The subtype known as chronic rhinosinusitis with nasal polyposis (CRSwNP) is distinguished by a significantly elevated recurrence rate and augmented challenges in the management of nasal polyps. The pathogenesis underlying this subtype remains incompletely understood. Macrophages play a crucial role in mediating the immune system's response to inflammatory stimuli. These cells exhibit remarkable plasticity and heterogeneity, differentiating into either the pro-inflammatory M1 phenotype or the anti-inflammatory and reparative M2 phenotype depending on the surrounding microenvironment. In CRSwNP, macrophages demonstrate reduced production of Interleukin 10 (IL-10), compromised phagocytic activity, and decreased autophagy. Dysregulation of pro-resolving mediators may occur during the inflammatory resolution process, which could potentially hinder the adequate functioning of anti-inflammatory macrophages in facilitating resolution. Collectively, these factors may contribute to the prolonged inflammation observed in CRSwNP. Additionally, macrophages may enhance fibrin cross-linking through the release of factor XIII-A (FAXIII), promoting fibrin deposition and plasma protein retention. Macrophages also modulate vascular permeability by releasing Vascular endothelial growth factor (VEGF). Moreover, they may disrupt the balance between Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs), which favors extracellular matrix (ECM) degradation, edema formation, and pseudocyst development. Accumulating evidence suggests a close association between macrophage infiltration and CRSwNP; however, the precise mechanisms underlying this relationship warrant further investigation. In different subtypes of CRSwNP, different macrophage phenotypic aggregations trigger different types of inflammatory features. Increasing evidence suggests that macrophage infiltration is closely associated with CRSwNP, but the mechanism and the relationship between macrophage typing and CRSwNP endophenotyping remain to be further explored. This review discusses the role of different types of macrophages in the pathogenesis of different types of CRSwNP and their contribution to polyp formation, in the hope that a better understanding of the role of macrophages in specific CRSwNP will contribute to a precise and individualized understanding of the disease.