β-glucan is a natural polysaccharide widely existed in cereals, bacteria, and fungi. In recent years, β-glucan has attracted much attention due to its broad immunomodulatory effects. It can directly modulate neutrophils, monocytes, and macrophages, leading to their metabolic and epigenetic reprogramming and exerting a direct modulatory effect on intrinsic immunity. Besides, it can also impact the differentiation of T and B cells and the release of inflammatory factors to regulate adaptive immunity. In addition, β-glucan has been reported to influence the body's immune response by regulating gut flora. This review summarizes the immunomodulatory effects and mechanisms of β-glucan, as well as the clinical applications of β-glucan in tumors, allergic diseases, infectious diseases, and other types of diseases. This review will provide a theoretical reference and scientific basis for the further development and utilization of β-glucan.

The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome is a macromolecular protein complex which detects danger signals and subsequently activates Caspase-1. This activation results in pyroptosis and the release of the IL-1β. Properly regulated NLRP3 inflammasome activity is essential for both sterile inflammation and host defense against microbial infections. However, aberrant activation of NLRP3 has been implicated in the pathogenesis of multiple diseases. Therefore, elucidating the mechanisms underlying NLRP3 activation is critical for advancing the understanding of how the immune system recognizes and responds to danger signals, and facilitating the development of targeted therapeutic interventions. Over the past two decades, multiple mechanistic models have been proposed, highlighting a complex and fine-tuned regulatory network. Nevertheless, the precise process of NLRP3 activation and the specific biological events it senses remain enigmatic. This review focuses on the widely accepted models of NLRP3 activation and the latest progress on its regulatory networks.

Obesity is the excessive accumulation of fat caused by the imbalance between energy intake and expenditure, which has become a global health issue. The metabolic homeostasis of adipose tissue plays a crucial role in the progression of obesity and has numerous impacts on systemic physiology. Studies have found that various immune cells and cytokines are involved in maintaining and regulating the metabolic homeostasis of adipose tissue, suggesting the significant potential of immune cells in alleviating obesity and insulin resistance (IR). From the perspectives of innate and adaptive immunity, this review discusses the progress on the role of immune cells in thermogenesis and metabolic functions of adipose tissue and further explores the therapeutic potential of the immune system in obesity and related metabolic disorders.

The purpose of this study is to explore the role and mechanism of peptidyl arginine deimidase type 4 (PAD4) in inflammatory adipose tissue. The subcutaneous and visceral adipose tissues of db/db (type 2 diabetes mellitus [T2DM] group), db/m (T2DM control group), ob/ob (obese group) and ob/c(obese control group) were extracted, and the expression of PAD4 in subcutaneous and visceral adipose tissue of T2DM and obese mice was detected by immunohistochemistry. Wild-type mouse primary peritoneal macrophages and mouse macrophage cell line RAW264.7 were stimulated with LPS, the expressions of PAD4, inflammatory factors TNF-α and IL-6, the activation of NF-κB signal pathway in the 2 types of cells were detected by qRT-PCR and Western blotting, respectively. The results showed that compared to those of the db/m and ob/c groups, the expression of PAD4 in subcutaneous and visceral adipose tissue, primary peritoneal macrophages and RAW264.7 cells stimulated by LPS in db/db and ob/ob groups were all decreased, while the expressions of inflammatory factors TNF-α and IL-6 increased significantly.Meanwhile, the TLR4/NF-κB signal pathway was activated. This study shows that the expression of PAD4 is decreased in subcutaneous and visceral adipose tissue in inflammatory state (T2DM and obesity) and is negatively correlated with the activation of the TLR4/NF-κB signal pathway.

The aim of this study is to explore the regulatory features, co-regulatory roles and effects on the epigenome of the STAT family proteins and the master transcription factors of the Th1, Th2, and Th17 subtypes, including the T-box expressed in T cell (T-bet), GATA binding protein 3 (GATA3), and retinoic acid receptor-related orphan receptor γt (RORγt) in Th differentiation. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) data of different T cell differentiation stages and chromatin immunoprecipitation sequencing (ChIP-seq) data of transcription factors were obtained and integrated from the GEO database. The co-localization, the genomic distribution of the transcription factors, and the chromatin accessibility changes during differentiation and functions of regulated genes were analyzed. The results showed that the transcription factor STAT2 was the main STAT family transcription factor involved in the maintenance of Th0 chromatin characteristics. STAT4 was widely co-localized with T-bet and regulated Th1 activation. The master regulator GATA3 and the co-factor STAT6 preferentially bound to non-promoter cis-elements thereby directing Th2 differentiation. RORγt, the master transcription factor, enhanced the binding strength of STAT3 and STAT5 in a distinctive manner independent of altered chromatin accessibility, co-regulating Th17-specific differentiation. This study suggests that STAT family transcription factors selectively participate in and differentially regulate Th differentiation.

To investigate the regulation of the G protein-coupled receptor 84 (GPR84) of macrophages and its role in acute lung injury, CRISPR/Cas9 gene editing technology was used to construct Gpr84 conditional knockout mice (Gpr84^loxp/loxp), which were subsequently hybridized with macrophage-specific Lyz2-Cre mice to generate the macrophage Gpr84 conditional knockout (cKO) mice. Next, the acute lung injury model was established by a single intratracheal administration of LPS (5 mg/kg) to the conditional knockout and C57BL/6 wild-type (WT) mice. The mice were divided into 4 groups: the WT-control, the cKO-control, the WT-LPS, and the cKO-LPS groups, with 6 animals in each group. The cKO mice were identified using PCR technology. H-E staining was employed to examine the pathological changes in lung tissue. The ratio of wet weight/dry weight (W/D) was measured in lung tissue, and qRT-PCR was utilized to quantify the expression of inflammatory factors, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (Hmox1) in lung tissue. ELISA was used to determine the levels of IL-1β, IL-6, and MCP-1 in mouse serum, and immunohistochemistry was performed to detect the protein level of Nrf2 in lung tissue. The results showed that the macrophage Gpr84 knockout mice were successfully constructed, and the function of GPR84 in acute lung injury was studied. Compared to the control group, the LPS group exhibited significant inflammatory cell infiltration and alveolar collapse, increased lung injury scores, elevated lung W/D ratio, and increased expression of inflammatory factors in lung tissue and serum. However, compared to the WT-LPS group, the cKO-LPS group showed reduced pulmonary inflammatory cell infiltration, decreased lung injury scores, and significantly reduced expression of inflammatory factors in lung tissue and serum. In addition, the expressions of Nrf2 and Hmox1, which have antioxidant functions, significantly increased. This study suggests that the specific knockout of the Gpr84 gene in macrophages can significantly alleviate LPS-induced lung inflammation and enhance the resistance to oxidative stress, indicating that GPR84 may serve as a potential target for the treatment of acute lung injury.

Macrophages are innate immune cells that mainly play roles in antigen presentation and phagocytosis. Macrophages are categorized to M1 and M2 types. M2 macrophages in different microenvironments can be further divided into 4 subtypes: M2a, M2b, M2c, and M2d. M1 macrophages are induced by IFN-γ and LPS, which promote inflammation, inhibit microbial and tumor growth while M2 macrophages are activated by IL-4 or IL-13, and have anti-inflammatory activity, and their functions include tissue homeostasis maintanence, immune regulation, phagocytosis, promoting angiogenesis, and influencing tumor formation and progression. The special functions of various phenotypes of macrophages are mainly controlled by polarization signals, which can activate macrophages by upregulating different transcription programs. This review focuses on the relationships between the three metabolic pathways (sugar metabolism, lipid metabolism and amino acid metabolism) and the polarization of different macrophages which provides new solutions for diseases related to macrophage polarization.

To investigate the effect of targeted knockdown of C-C motif chemokine ligand 3 (CCL3) expression in alleviating sepsis-induced acute lung injury (ALI) and the underlying mechanism, an induced mouse sepsis model was established by cecal ligation and puncture (CLP). Lung tissue samples were collected, and differentially expressed genes and enriched pathways were identified by RNA sequencing (RNA-seq） analysis. Small interfering RNA (siRNA) technology was used to specifically knockdown the expression of the key gene CCL3, and si-CCL3 plasmids were injected via the tail vein for in vivo intervention. Mice were randomly divided into 3 groups according to the experimental design: the sham operation control group, the sepsis model group, and the si-CCL3 silencing group. H-E staining was used to evaluate the degree of lung tissue pathological damage, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining was used to detect the level of cell apoptosis. The results showed that the sepsis mouse model was successfully established by CLP. RNA-seq results indicated that compared with the control group, there were 475 up-regulated genes and 467 down-regulated genes in the lung tissue of sepsis mice, among which the up-regulation of CCL3 was the most significant. The relative expression of CCL3 mRNA in mouse lung tissue was detected by qRT-PCR, and the results were consistent with those of the RNA-seq, showing that CCL3 was significantly up-regulated in the lung tissue of mice with sepsis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis results showed that the NF-κB signaling pathway and ferroptosis marker proteins glutathione peroxidase 4 (GPX4) and prostaglandin-endoperoxide synthase 2 (PTGS2) were all involved in the process of sepsis-induced ALI. The results of qRT-PCR and Western blotting were consistent with RNA-seq results. After treatment with si-CCL3 plasmids, the pathological changes in the lung tissue were significantly improved, the structure of bronchi and alveoli was significantly restored, the thickness of alveolar septum was reduced, and interstitial exudation was decreased. TUNEL staining results showed that the number of apoptotic cells in the si-CCL3 silencing group was significantly lower than that of the sepsis model group (P<0.05). In conclusion, targeted knockdown of the chemokine CCL3 expression can alleviate the process of sepsis-associated acute lung injury by inhibiting the ferroptosis phenotype in lung tissue.

This study aimed to identify the B cell phenotypic characteristics in atherosclerotic plaques and explore the potential relationship between B cells and plaque inflammation progression. By comparing the immune cell profiles from single-cell sequenicing data of plaques and peripheral blood in atherosclerotic patients, 2 CD83⁺B cell clusters enriched in human atherosclerotic plaques were identified, with increased percentages of 46.74% and 19.18%, respectively. Compared to other B cell subpopulations, CD83⁺B cells expressed higher levels of aging-related genes including CDKN1A, IL-6, TNF-α, MALAT1, and GADD45B, suggesting that the increased CD83⁺B cells in plaques exhibited a senescent phenotype. To validate these findings, ApoE gene knockout (ApoE^-/-) mice were fed with Western diet (WD) to induce atherosclerosis. The proportion of CD83⁺ B cells in total B cells was significantly higher in the arterial tissues of WD mice (fold change=5.36，P=0.010 8). Consistently, in WD mice, the average fluorescence intensities of senescence-associated inflammatory cytokines including IL-6, TNF-α, and IFN-γ in CD83⁺B cells were significantly higher than those of the CD83^-B cells, with significant fold changes of 1.95 (P=0.020 2), 4.25 (P=0.003 0), and 4.20 (P=0.016 9), respectively. This study reveals that CD83⁺B cells are enriched in atherosclerotic plaques and exhibit a senescence-like phenotype, producing higher levels of senescence-associated inflammatory factors that may contribute to arterial inflammation.

In order to explore the mechanism of interaction between C-X-C motif chemokine ligand 13 (CXCL13) and glycosaminoglycan in autoimmune diseases, C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptides to establish the experimental autoimmune encephalomyelitis (EAE) model. On the 3rd day post-immunization, the modeled mice were randomly divided into 3 groups: the control group, the group treated with mutant mouse CXCL13 protein which lacked the glycosaminoglycan binding capacity (the mutant group), and the group treated with mouse CXCL13 protein (the wild type group). Corresponding protein intervention was performed respectively. Disease scoring was continued. Flow cytometry was used to detect mouse spleen B cells and plasma cell subsets on day 7 and day 14 post-immunization, and the expressions of IgG and IgM in plasma and CXCL13 in spinal cord and plasma were measured by ELISA. Tissue section and transcriptome sequencing of splenic cells were analyzed. The results showed that the wild type group had delayed onset and significantly lower disease scores than the control group (P=0.031 3), while those of the mutant group was between the control group and the wild type group. On the 7th day after immunization, compared to the control group, both the mutant group (P=0.017 2) and the wild type group (P=0.000 2) showed an increased proportion of germinal center B cells and decreased proportion of plasmablasts (P=0.022 3 in the mutant group, P=0.000 1 in the wild type group); On the 14th  day after immunization, compared to the control group, both the mutant group (P=0.000 5) and the wild type group (P=0.003 1) showed an increased proportion of germinal center B cells, while the proportions of plasmablasts (P=0.005 8 in the mutant group, P=0.027 9 in the wild type group) and plasma cells decreased (P=0.002 1 in the mutant group, P=0.034 5 in the wild type group). On day 14 post-immunization, the plasma subsets basically maintained the same trend as day 7 post-immunization, but the germinal center B subsets composition changed dynamically. The plasma IgM level of the wild type group decreased significantly in the early stage of the immune response (P=0.004 6). However, on day 14 post-immunization, compared to that of the control group, the plasma IgG levels in the mutant group (P=0.006 1) and the wild type group (P=0.001 8) increased significantly. The plasma IgM levels in the mutant group (P=0.012 3) and the wild type group (P=0.009 1) also increased significantly. The plasma IgG affinity detection showed that the affinity between IgG and MOG peptides in the control group was higher than that in the other two groups (P=0.038 0). The myelin staining analysis of the spinal cord lumbar enlargement plane sections showed that the demyelination degree was consistent with the trend of disease scores. The transcriptome sequencing data of splenic cells also showed that over time, the differentially expressed genes in the mutant group were more enriched in the humoral immune pathway. This study suggests that the CXCL13-glycosaminoglycan interaction is involved in the antibody production process and mediates the immune response.

This study was designed to explore the potential relationship between myocardial fibrosis and the pyroptosis of mouse cardiac fibroblast (MCF) regulated by soluble growth stimulation expressed gene 2 (sST2). A mouse model of viral induced myocarditis (VMC) was established, and mice were divided into the VMC group and the VMC+ST2 antibody group in addition to a control group. Mice were sacrificed on the 7th day and cardiac inflammatory infiltration was observed by H-E staining and collagen deposition was observed by Masson staining. Western blotting was conducted to detect the expressions of NOD-like receptor family pyrin domain-containing protein 3 (NLRP3), IL-1β, cleaved caspase-1, GSDMD-N, and activation markers collagen Ⅰ/Ⅲ and α-SMA after sST2 treatment of MCF. After MCC950 pretreatment, the expressions of NLRP3, IL-1β, cleaved caspase-1, GSDMD-N, and activation markers collagen-Ⅰ/Ⅲ and α-SMA were detected. The mRNA expressions of IL-1β, IL-18, NLRP3, collagen-Ⅰ/Ⅲ and α-SMA after MCC950 pretreatment were detected by qRT-PCR. The results showed that the expressions of NLRP3, IL-1β, IL-18, cleaved caspase-1, and GSDMD-N were significantly increased after sST2  treatment of MCF. Activation indexes collagen-Ⅰ/Ⅲ and α-SMA were up-regulated. After MCC950 pretreatment, the expressions of NLRP3, IL-1β, IL-18, cleaved caspase-1, and GSDMD-N were down-regulated. The activation indexes of collagen-I/III and α-SMA were significantly reduced. In vivo ST2 blockage caused reduced myocardial inflammatory infiltration and collagen deposition. In conclusion, sST2 activates NLRP3 inflammasome to induce MCF pyroptosis and promote myocardial fibrosis.

This study aimed to investigate the role of IL-6 in diffuse large B-cell lymphoma (DLBCL) and the role of IL-6 on cell apoptosis, proliferation, invasion and migration via the JAK/STAT3 signaling pathway. OCI-LY8 cell line was used as a DCBCL model and drug intervention of IL-6 or STAT3 gene silencing were used to assess the effect of IL-6 and STAT3 on OCI-LY8 cells. Cell viability was detected by CCK8 assay and apoptosis rate was determined by flow cytometry to study the effect of IL-6 on the proliferation and apoptosis of DLBCL cells. Transwell assay and scratch assay were used to detect cell invasion and migration capacity and elucidate the effect of different IL-6 concentrations on DLBCL migration. The expressions of JAK, STAT3 and the downstream apoptosis-related B cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and survivin proteins were detected by Western blotting. Western blotting showed that IL-6 up-regulated anti-apoptotic proteins Bcl-2 and survivin, and downregulated pro-apoptotic protein Bax by activating the JAK/STAT3 pathway, thereby inhibiting OCI-LY8 apoptosis. IL-6 could also enhance the invasion and migration of OCI-LY8 by activating STAT3. The effect of IL-6 was reversed upon IL-6 inhibitor LMT-28 treatment or STAT3 silencing. IL-6 enhanced the invasion and migration capacity of OCI-LY8 DLBCL cells by activating the JAK/STAT3 signaling pathway, as well as increasing their anti-apoptosis ability. Together, these findings reveal that IL-6 promotes DLBCL development via the JAK/STAT3 pathway, which provides a new potential target and theoretical basis for DLBCL treatment.

To analyze the effect of total alkaloids of Strychni Semen on the apoptosis of synovial cell and on the Wnt3a/β-catenin signaling pathway in rheumatoid arthritis (RA) rat, a total of 40 SPF-level SD rats were prepared, with 10 for the control group and 30 for the RA model group. Twenty-seven rats in total were successfully modeled and were divided into the model group, the total alkaloids of Strychni Semen group, and the total alkaloids of Strychni Semen+Wnt3a agonist group, with 9 rats per group. Histopathological features, toe-swelling degree, arthritis index, immune organ index, synovial cell apoptosis rate, inflammatory factors concentration, and Wnt3a/β-catenin pathway gene transcription and expression were measured in each group. The results showed that the synovial tissue structure of the control group was normal without hyperplasia or inflammatory infiltration. In the model group, the synovial tissue shape was rough, with hyperplasia and infiltration of inflammatory cells. The synovial hyperplasia and inflammatory infiltration were alleviated in the total alkaloids of Strychni Semen and the total alkaloids of Strychni Semen+Wnt3a agonist groups. Compared to those of the control group, toe swelling, arthritis index, thymus index, spleen index, IL-6, IL-17, IL-1β, and TNF-α levels, Wnt3a, β-catenin mRNA and protein expression levels increased in the model group, while the apoptosis rate of synovial cells decreased. Compared to those of the model group, toe swelling, arthritis index, thymus index, spleen index, IL-6, IL-17, IL-1β, and TNF-α levels, Wnt3a, β-catenin mRNA and protein expression in the total alkaloids of Strychni Semen group were decreased, while the apoptosis rate was increased. Compared to the total alkaloids of Strychni Semen group, the total alkaloids of Strychni Semen+Wnt3a activator group showed increased toe swelling, arthritis index, thymus index, spleen index, IL-6, IL-17, IL-1β, and TNF-α concentrations, Wnt3a, β-catenin mRNA and protein expression levels and decreased apoptosis rate of synovial cells (all above with P＜0.05). In conclusion, total alkaloids of Strychni Semen can inhibit intraarticular inflammation and promote synovial cell apoptosis in RA rats by modulating the Wnt3a/β-catenin signaling pathway.

Autoimmune diseases are chronic conditions characterized by the erroneous attack of immune system towards self-tissues and organs, characterized by abnormal activation of self-reactive T and B cells, production of autoantibodies, and persistent tissue inflammation. Common examples include rheumatoid arthritis, systemic lupus erythematosus, and immune thrombocytopenia, which may lead to multi-organ dysfunction. Recent research progress has revealed significant metabolic reprogramming in immune cells associated with these diseases. Metabolic reprogramming refers to the process in which cells adjust metabolic pathways to adapt to survival needs in different microenvironments. In these diseases, metabolic reprogramming primarily manifests as a shift from oxidative phosphorylation to glycolysis. This metabolic alteration not only provides energy for cell activation but also directly influences their immunosuppressive and immunomodulatory functions. Based on these findings, researchers have developed various metabolic regulatory strategies, such as glycolysis and mTOR pathway inhibitors, offering new approaches for the diagnosis and treatment of autoimmune diseases. Advances in this field hold promise for improving patient prognosis and facilitating the development of personalized therapy.

To study the molecular mechanism by which the N6-methyladenosine (m6A)-reading protein YTHDC2 regulates macrophage M1 polarization, the expression level of YTHDC2 protein was detected in a macrophage polarization model. Next, the expressions of polarization markers was detected in YTHDC2 knockdown M1 macrophages. YTHDC2 knockdown M1 macrophages were constructed, and YTHDC2 knockdown and wild type M1 macrophages were sequenced using Illumina Novaseq JP26000/MGISEQ-T7 sequencing platform to identify the differentially expressed genes of the 2 cell groups. The differentially expressed genes were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment methods to explore the YTHDC2 regulatory pathway and screen for YTHDC2 downstream target genes. Cellular experiments were used to reveal the role of YTHDC2 downstream target gene fibulin 1 (FBLN1) in M1 macrophages. The results showed that YTHDC2 expression was elevated in M1 macrophages. Expression levels of polarization markers were decreased in YTHDC2 knockdown M1 macrophages. 147 differentially expressed genes were identified between YTHDC2 knockdown and wild type M1 macrophages. FBLN1 expression is up-regulated in YTHDC2 knockdown M1 macrophages. Potential m6A methylation might occur at multiple sites in FBLN1. Expression levels of polarization markers were increased in M1 macrophages with the knockdown of YTHDC2 and FBLN1. In conclusion, YTHDC2 may promote macrophage M1 polarization by regulating the m6A modification of FBLN1.

The aim of this study is to understand the distribution of autoantibodies in systemic lupus erythematosus (SLE) patients and explore the role of SLE autoantibodies in organ function. Seventy-six newly diagnosed SLE patients admitted to the Second Hospital of Jiaxing  from January 2018 to December 2023 were selected. Indirect immunofluorescence was used to detect the autoantibodies index, and the data were analyzed. The results showed that most SLE patients suffered from arthritis (55.26%) and rash (52.63%). The positive rate of antinuclear antibody (ANA) was 100.00%, and among them the most common was the anti-Sjogren's syndrome A (SSA) antibody. Multiple autoantibodies in the vast majority of patients were positive (97.37%). The positive rate of anti-dsDNA antibody was the highest in the adolescent group (66.67%), but the lowest in the elderly group (33.33%). The positive rate of anti-dsDNA antibody in lupus nephritis (LN) was 76.47%. The positive rate of anti-Sm antibody was the highest in Raynaud＇s phenomenon and alopecia patients (33.33% and 50.00% respectively). The positive rate of anti-histone antibody (AHA) in vasculitis and LN patients was 75.00% and 58.82%, respectively. This study suggests that the clinical manifestations of SLE are different and highly heterogeneous, and multiple autoantibodies are correlated with organ involvement, clinical manifestations and age.

This study investigated the role of IL-33 knockdown in attenuating airway inflammation in a mouse asthma model, aiming to identify novel therapeutic targets for asthma. Bone marrow-derived mesenchymal stem cells (BMMSC) were isolated from mice and transduced with IL-33-silencing plasmids (si-IL-33-1^#, si-IL-33-2^#, si-IL-33-3^# and a scrambled control plasmid ) via lentiviral system. The efficiency of IL-33 knockdown was validated by qRT-PCR. An asthma mouse model was established using a combined sensitization and challenge protocol with ovalbumin (OVA). Mice were divided into 5 groups: the control group; the asthma model group; the BMMSC-treated group; the BMMSC+empty vector group and the BMMSC+IL-33 knockdown group. Pathological changes in lung tissues were assessed by H-E staining, Masson's trichrome staining, and immunohistochemistry (IHC). Serum levels of IL-33, IL-1β, and IL-6 were quantified using ELISA. The result showed that primary BMMSC exhibited adherent growth with spindle or polygonal morphology. Flow cytometry was used to measure the expressions of surface markers: CD90 positivity rate was 99.30%; CD29 positivity rate was 100.00%; while hematopoietic lineage markers CD45 and CD34 showed minimal positivity (0.34% and 1.24%, respectively). qRT-PCR demonstrated that the si-IL-33-3^# plasmid effectively silenced IL-33 expression in BMMSC, confirming that it was an optimal IL-33 knockdown construct. Histopathological analysis revealed the BMMSC+IL-33 knockdown group displayed minimal inflammatory cell infiltration in lung tissue, with intact bronchial epithelium. IHC staining showed that BMMSC+IL-33 knockdown group exhibited significantly reduced α-smooth muscle actin (α-SMA) and vascular endothelial growth factor B (VEGFB) relative expressions compared to those in the asthma model group and the BMMSC-treated group (P<0.05). ELISA analysis further confirmed the markedly decreased serum levels of IL-1β, IL-6, and IL-33 in the BMMSC+IL-33 knockdown group compared to either the model or the BMMSC-treated groups (P<0.05). Altogether, IL-33 knockdown attenuates inflammatory response in the asthma mouse model and thereby prevents the lung lesions associated with asthma. 

2025年8月29~30日，以“聚力同行，共创未来”为主题的2025年免疫学前沿进展学术年会在上海成功举办。本次年会由上海市免疫学会主办，其官方学术期刊《现代免疫学》杂志亦全程参与支持，汇聚了60余位国内外领军学者及超800名参会代表，共同探讨免疫学前沿发展趋势。

 年会特邀储以微教授、Tiffany Horng教授、郑利民教授、郑颂国教授及李华兵教授等知名专家作主旨报告，各位学者围绕各自研究领域的前沿突破展开深度分享，呈现了一场高水准的学术盛宴。会议同步设置皮肤免疫、眼免疫、神经免疫、移植免疫、交叉免疫、感染免疫、风湿免疫、中医药免疫八大专题分会场，有效推动基础研究、临床转化与生物技术等跨学科领域的深度碰撞与融合。 

本次年会不仅为免疫学界搭建了高水平的学术交流平台，更依托《现代免疫学》等专业期刊的学术传播优势，加速了科研成果向临床应用及产业转化的进程。此次盛会的成功举办，进一步凝聚了我国免疫学领域的创新力，为推动学科发展注入了新的动能。

This study aimed to develop the optimal enzymatic combination for single-cell suspension from mouse lung, and to explore the isolation and culture of the type 2 innate lymphoid cells (ILC2) using immunomagnetic bead separation and flow cytometry. 10 mice were divided into 4 groups for different enzymatic isolation methods, including collagenase Ⅳ, Lung Dissociation Kit, Liberase TM, and collagenase P+dispase Ⅱ, respectively. The most optimal enzymatic isolation method was chosen based on the ratio of living, CD45⁺ and c-kit⁺ cells. Immunomagnetic bead enrichment (EasySep Mouse ILC2 Enrichment Kit) and FACS were used to isolate ILC2 and flow cytometry was used to measure ILC2 homogeneity．Cells cultured in vitro were divided into 2 groups by treatment of IL-33 to evaluate its promoting effect on the in vitro culture of ILC2. Western blotting was used to detect the protein levels of GATA binding protein 3 （GATA-3）, IFN-γ, IL-5 and IL-13. The results indicated that the combination of collagenase P+dispase Ⅱ was the most suitable method for cell isolation of mouse lung with higher ratios of target cell and better cost-effectiveness. The percentage of ILC2 in the enriched fraction reached 2.14% compared to less than 1% before enrichment. The expressions of IFN-γ, IL-5, IL-33 with IL-33 stimulation were higher than those of the control（P<0.001). However, GATA-3 expression showed no statistical significance between the 2 groups（P>0.05). In conclusion，collagenase P+Dispase Ⅱ is a feasible enzymatic digestion protocol for mouse lung tissue. The magnetic cell sorting system could be a rapid and efficient method for ILC2 isolation and future cultivation. In addition, IL-33 can enhance the viability of ILC2 in vitro and stimulate the expression of downstream cytokines. 

The aim of this study was to investigate the therapeutic effect of acacetin on depressed rats and its regulation on the HIF-1α/NLRP3 signaling pathway. A rat model of depression was established, and rats were divided into the model group, the acacia low-dose group, the acacia high-dose group and the acacia high-dose + pathway activator group (acacia high-dose+BMS-986299 group), with 12 rats in each group, in addition to a control group. After the treatment was completed, the sugar water preference, the mine field experiment, and the forced exercise experiment were performed, respectively. ELISA was used to detect levels of inflammatory and oxidative stress factors. H-E and Nissl staining were used to observe the histopathological morphology and neuronal number of hippocampus. Western blotting was used to detect the expression of proteins related to the HIF-1α/NLRP3 signaling pathway. Compared to those of the control group, the hippocampal tissue structure of the model group was damaged, the pyramidal cell arrangement was disordered, the nuclear condensation phenomenon was obvious, and the numbers of Nissl bodies and neurons decreased. In the meantime, the sugar water preference rate, voluntary activity score, and the level of CAT were decreased, whereas the immobility time of forced swimming, the levels of IL-6, IL-β, TNF-α, reactive oxygen species (ROS), malondialdehyde (MDA), and the expression of HIF-1α, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 were increased (P<0.05). Compared to those of the model group, the hippocampal tissue structure of the acacia low-dose and high-dose groups was relatively normal, and the pyramidal cells were relatively intact and well arranged, the nuclear condensation phenomenon was reduced, and the numbers of Nissl bodies and neurons increased. Consistently, the sugar water preference rate, voluntary activity score, and the level of CAT increased, while the immobility time of forced swimming, the levels of IL-6, IL-β, TNF-α, ROS, MDA, and the expression of HIF-1α, NLRP3, ASC and caspase-1 decreased (P<0.05). Compared to those of the acacia high-dose group, the hippocampal tissue structure damage and pyramidal cell arrangement disorder were aggravated in the acacia high-dose +BMS-986299 group. The nuclear condensation phenomenon was intensified and the numbers of Nissl bodies and neurons decreased. The sugar water preference rate, voluntary activity score, and the level of CAT decreased, while the immobility time of forced swimming, the levels of IL-6, IL-β, TNF-α, ROS, MDA, and the expression of HIF-1α, NLRP3, ASC and caspase-1 were increased (P<0.05). Together, these findings demonstrate that acacetin has therapeutic effect on depression rats, and underlying mechanism is related to the inhibition of the HIF-1α/NLRP3 signaling pathway.

To investigate the effect of kaempferol on nasal mucosal injury in allergic rhinitis (AR) rats via the TLR4/NF-κB/TNF-α signaling pathway, rat AR model was established. Subjects were randomly divided into the model group, the low-dose (50 mg/kg) kaempferol group, the high-dose (100 mg/kg) kaempferol group, and high-dose (100 mg/kg) kaempferol+LPS (0.4 mg/kg) group as well as the control group. Rhinitis symptoms in rats were observed and scored after drug intervention. H-E staining was applied to observe the pathological changes in rat nasal mucosal tissues. ELISA was used to detect the levels of IL-6, TNF-α in rat nasal lavage fluid (NLF) and of serum IgE. Western blotting was used to detect the protein expressions of TLR4, NF-κB, and TNF-α in nasal mucosal tissues. The results showed that the rhinitis symptom score of the model group was significantly higher than that of the control group (P＜0.05). In addition, pathological changes in the nasal mucosal tissue of the model group were obvious. The levels of IL-6, TNF-α in NLF, IgE in serum, and the protein expressions of TLR4, NF-κB, and TNF-α in nasal mucosal tissues were also significantly increased (all with P＜0.05). Compared to the model group, the medicated rats showed decreased rhinitis symptom scores (both P＜0.05) and alleviated pathological injury. The levels of IL-6, TNF-α in NLF, IgE in serum, and the protein expressions of TLR4, NF-κB, and TNF-α in nasal mucosal tissues were also all decreased. These observations were particularly evident in the high-dose kaempferol group (all with P＜0.05). In contrast, LPS, the TLR4 activator, reversed the effects of kaempferol on AR rats (all with P＜0.05). In summary, kaempferol inhibits the TLR4/NF-κB/TNF-α signaling pathway and alleviates the pathological injury and inflammatory responses of nasal mucosa in AR rats, which in turn improves the disease symptoms.

To explore the neuroprotective effect of Huanglian Jiedu Tang on Parkinson's disease (PD) cell model by the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome pathway, a PD cell model was established by adding 6-hydroxydopamine (6-OHDA) to human neuroblastoma cells (SH-SY5Y). The serum of rats gavaged with Huanglian Jiedu Tang was obtained and cells were treated with different concentrations of drug drug-containing serum or blank serum. The concentration of drug-containing serum was screened using the CCK-8 method. ELISA was used to detect the content of lactate dehydrogenase (LDH) in the cell supernatant. Flow cytometry was used to detect cell apoptosis and the expression of reactive oxygen species (ROS). β-galactosidase staining was used to detect cellular aging. Immunofluorescence assay was used to detect the expression of α-synuclein (α-Syn) and phosphorylated α-Synuclein (p-α-Syn). Western blotting was used to detect the protein expressions of NLRP3, caspase-1 and its precursors pro-Caspase-1, α-Syn, IL-1β and its precursor pro-IL-1β, and IL-18 in each group. Compared with the model group, the low, medium, and high dose Huanglian Jiedu Tang groups showed reduction of LDH content, cell apoptosis rate, and the β-galactosidase increase caused by PD. In contrast, the treatments inhibited the protein expressions of NLRP3, caspase-1, α-Syn, p-α-Syn, IL-1β and IL-18. In summary, Huanglian Jiedu Tang inhibits the inflammation damage of SH-SY5Y cells in PD model induced by 6-OHDA, possibly by regulating the NLRP3 inflammasome pathway, which provides a theoretical basis for the treatment of PD with Huanglian Jiedu Tang.

Peripheral helper T cells (Tph) have been identified in recent years as a CD4⁺T cell subset. Tph are characterized by the secretion of C-X-C motif chemokine ligand 13 (CXCL13), and the expression of surface molecules including PD-1, inducible costimulatory (ICOS), HLA-DR, etc. By expressing chemokine receptor C-C motif chemokine receptor 2 (CCR2), C-X3-C motif chemokine receptor 1 (CX3CR1), and CCR5, Tph can be recruited to inflammatory sites and promote the formation of tertiary lymphoid structures (TLS). Through interaction with IL-21 and signaling lymphocytic activation molecule family (SLAMF), Tph assist B cell maturation, differentiation, and antibody production. Tph are shown to be involved in the pathogenesis of many autoimmune diseases. Herein, this review discusses the biological characteristics of Tph and their role in different types of autoimmune diseases to further reveal their mechanism of action and clinical value, and provide new ideas for future targeted therapy.

This study explores the potential mechanism by which dihydroartemisinin (DHA) modulates the complement C3/C3a receptor (C3aR) signaling pathway to improve neuroinflammation in the hippocampus in a mouse depression model. Forty male C57BL/6J mice aged 8 weeks were randomly divided into 4 groups: the control group, the model group, the low-dose DHA (DHA-L) group, and the high-dose DHA (DHA-H) group, with 10 mice in each group. Except for the control group, the remaining groups were subjected to chronic unpredictable mild stress (CUMS) to establish the depression model. Behavioral assays were performed to evaluate the success or failure of the model and changes in depressive behaviors in the mice. H-E staining and Nissl staining were used to assess neuronal pathological damage in the hippocampus. ELISA was employed to detect inflammatory cytokine levels, while immunohistochemistry was used to observe microglial activation. Western blotting was performed to detect the expression levels of C3 and C3aR proteins. The results showed that the depression model in mice was successfully established. Mice in the model group showed a significant decrease in sucrose preference, time spent in the center of the open field, and total distance traveled in the open field compared to the control group (P<0.01). In the tail suspension and forced swimming tests, the immobility time of modeled mice was significantly prolonged (P<0.001). Mice in the DHA-L group and the DHA-H group showed a significant increase in sucrose preference, time spent in the center of the open field, and total distance traveled compared to the model group (P<0.05). Furthermore, their immobility time in the tail suspension and forced swimming tests was significantly reduced (P<0.05). The inflammatory cytokine levels in the hippocampus of the model mice were significantly higher than those in the control group (P<0.01), and DHA treatment significantly reversed this effect (P<0.05). DHA treatment also alleviated the pathological damage to hippocampal neurons in the model mice. The number of activated microglia in the hippocampus of the model group was significantly increased compared to that of the control group (P<0.001), whereas DHA treatment significantly reduced microglial activation compared to the model group (P<0.05). The expression levels of C3 and C3aR in the hippocampus of model mice were significantly higher than those in the control group (P<0.01), and DHA treatment significantly downregulated the expression of these proteins (P<0.05). In conclusion, the antidepressant effect of DHA may be mediated by reducing neuroinflammation in the hippocampus, and the mechanism is likely associated with the C3/C3aR signaling pathway.

The aim of the study is to investigate the mechanism by which C-C motif chemokine ligand 2 (CCL2) regulates the progression of cervical cancer (CC) through ferroptosis in the tumor microenvironment (TME). Cervical cancer-derived HeLa cells were transfected with shRNA targeting CCL2 (sh-CCL2#1) and CCL2 over-expressing cDNA (ova-CCL2) lentivirus, respectively. The in vitro proliferation of tumor cells was evaluated by the CCK-8 assay, and the metastasis and invasion abilities were assessed by the Transwell assay. Phorbol 12-myristate 13-acetate (PMA) was used to induce THP-1 differentiation, which was co-cultured in a 1∶4 ratio for 48 h with HeLa cells transfected with lentivirus mentioned above. Western blotting and qRT-PCR were used to measure the expression of macrophage polarization markers. The co-cultured cells in each group were further treated with ferroptosis inducer erastin, and the expressions of ferroptosis markers in macrophages were detected. The results showed that compared with the NC group, the HeLa cells of CCL2 over-expression group showed macrophage-dependent tumor-promoting phenotype (P<0.001). The macrophages in the TME underwent M2-type polarization, which was reversed upon the administration of erastin. In summary, overexpression of CCL2 in HeLa cells promotes the M2-type polarization of macrophages in the TME, which in turn stimulates the proliferation, migration, and invasion of HeLa cells. Reversion of the macrophage polarization by ferroptosis inducers disrupts the TME and inhibits tumor cell aggressive behavior. Therefore, inducing macrophage ferroptosis in the TME may help to suppress tumor progression.

The aim of this research is to explore the effect of adenosine A2A receptor (A2AR) blockade on the angiogenesis in thyroid cancer by regulating macrophage polarization. THP-1 cells were induced to differentiate into macrophages by phorbol ester which were subsequently divided into the shA2AR group and the shA2AR-NC group. The shA2AR and shA2AR-NC lentivirus was transfected into the two groups respectively. Western blotting was used to verify the blocking efficiency of A2AR, and flow cytometry was used to detect the polarization status of macrophages in each group. Next, the two groups of macrophage were co-cultured with human thyroid cancer cell TPC-1 for 24 h. The supernatants of TPC-1 co-culture were added into the corresponding human umbilical vein endothelial cells (HUVECs) groups: the shA2AR co-culture supernatant group and the shA2AR-NC co-culture supernatant group. The angiogenesis was measured and the expressions of vascular endothelial growth factor A (VEGFA) , vascular endothelial cadherin (VE-cadherin) and the activation of Notch1/JAK2/STAT3 signaling pathway were detected by Western blotting. The proliferation of HUVECs was detected by CCK-8 assay. The results showed that the expression of A2AR in macrophages was blocked by lentivirus transfection, and the macrophages were mainly polarized to M1 type. Compared to that of the shA2AR-NC co-culture supernatant group, the HUVECs proliferation activity in the shA2AR co-culture supernatant group was significantly decreased (P<0.01), as well as the expressions of VEGFA and VE-cadherin (P<0.01). The number of blood vessel formed was significantly reduced (P<0.01), and the activation of the Notch1/JAK2/STAT3 signaling pathway was significantly inhibited. Upon Notch1 receptor agonist Jagged1 treatment, the HUVECs in the shA2AR co-culture supernatant group showed increased activation of the Notch1/JAK2/STAT3 signaling pathway (P<0.01). In summary, the study reveals that blocking A2AR may induce macrophage M1 type polarization. By inhibiting the activation of the Notch1/JAK2/STAT3 signaling pathway, A2AR blockade reduces HUVECs proliferation and angiogenesis of thyroid cancer.

Macrophage extracellular traps (MET) are reticular structures composed of DNA and protein components secreted by activated macrophages. The formation process mainly includes mechanisms such as nicotinamide adenine dinucleotide phosphate oxidase (NOX)/reactive oxygen species (ROS)-dependent or -independent systems and histone citrullination mediated by peptidyl arginine deiminases (PAD). It is a new immune mechanism of macrophages, which can capture and kill bacteria, fungi, parasites, and other pathogenic organisms. However, some pathogenic organisms can escape the effect of MET during infection. This review mainly discusses the formation mechanism of MET and their role in resistance to pathogens, aiming to provide new targets for the treatment of diseases caused by pathogens.

This study aims to elucidate the inhibitory effects and underlying mechanisms of allicin on fibrosis in mouse cardiac fibroblasts (CF) through long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3). Mouse CFs were isolated and cultured, and an in vitro fibrosis model of CFs was established. The fibrotic CFs were treated with allicin at concentrations of 10, 20, and 40 μg/L to evaluate the protective effect of allicin on CF injury. Subsequently, cells were transfected with the sh-lncRNA MEG3 plasmid or the sh-lncRNA NC plasmid. The cells were divided into the control group, the model group, the allicin group, the sh-lncRNA MEG3 group, the sh-lncRNA NC group, the allicin + sh-lncRNA MEG3 group, and the allicin + sh-lncRNA NC group. CCK-8 assay was used to evaluate cell proliferation, flow cytometry was employed to assess cell apoptosis, and qRT-PCR was conducted to measure the expression changes of matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, lncRNA MEG3, and inflammatory cytokines (IL-8, IL-6, IL-1β). Western blotting was used to detect the expressions of alpha-smooth muscle actin (α-SMA), collagen type Ⅰ (COL1), collagen type Ⅲ (COL3), and proteins involved in the NF-κB signaling pathway (NF-κB p65, p-NF-κB p65, inhibitor of κB ［IκB］ , and p-IκB). The results showed that compared to the control group, the model group showed enhanced cell proliferation (P<0.01), reduced apoptosis rate (P<0.01), upregulated lncRNA MEG3 levels (P<0.01), and increased mRNA levels of MMP-2, MMP-3, MMP-9, as well as IL-8, IL-6, and IL-1β (P<0.01). After allicin treatment, cell proliferation was inhibited (P<0.01), apoptosis rate increased (P<0.01), and the mRNA levels of MMP-2, MMP-3, MMP-9, as well as IL-8, IL-6, and IL-1β were downregulated (P<0.05) in a dose-dependent manner. In addition, allicin downregulated the protein expressions of α-SMA, COL1, and COL3, as well as the p-NF-κB p65/NF-κB p65 ratio (P<0.01), while upregulating the p-IκB/IκB ratio (P<0.01) in the CFs fibrosis model. Compared to the model group, both the sh-lncRNA MEG3 group and the allicin group showed similar trends. Moreover, the combined treatment of allicin and sh-lncRNA MEG3 generated stronger inhibitory effect on CF injury than of sh-lncRNA MEG3 alone. This study suggests that allicin exerts a protective effect against fibrosis induced CF injury by downregulating lncRNA MEG3, thereby inhibiting the NF-κB pathway to suppress CFs proliferation, and reduce the levels of MMPs, inflammatory cytokines, and collagen deposition proteins.

IL-17D is a member of the IL-17 cytokine family which consists of 6 members, including IL-17A to IL-17F. The IL-17 receptor （IL-17R） family consists of 5 members: IL-17RA to IL17RE. IL-17A, as the typical representative of the IL-17 family and a hallmark cytokine produced by Th17 cells, plays a significant role in autoimmune diseases, tumorogenesis and inflammatory response. Although IL-17D is similar to IL-17A in the potential to elicit inflammatory cytokine production, studies on IL-17D are relatively fewer compared to those of IL-17A, and its function and mechanism of action remain elusive. In recent years, it has been found that IL-17D plays an important role in various diseases such as inflammatory response, viral infection, tumor and cardiovascular diseases, etc. By interacting with receptors on the surface of target cells, IL-17D activates downstream signaling pathways, regulates the expression of inflammatory factors, chemokines, etc., and participates in the recruitment and activation of immune cells. In addition, IL-17D has potential therapeutic value in antiviral immunity and tumor immunosurveillance. The review summarizes the structural features, biological activity and expression of IL-17D and its correlation with diseases.

The retrospective study aimed to investigate the correlation between the expression levels of free CD44 and CD69 in peripheral blood during early pregnancy and the occurrence of preeclampsia, in addition to evaluate the correlation with the disease severity and neonatal  outcome. One hundred pregnant women cases  with preeclampsia admitted to The First Affiliated Hospital of Shenzhen University (Shenzhen Second People's Hospital) from 1/1/2018 to 12/31/2023 were enrolled as the preeclampsia group, and 100 healthy pregnant women enrolled during the same time period were set as the control group. Clinical baseline data including age, body mass index (BMI), blood pressure, BMI at admission, blood pressure at admission, random urine protein quantification, gestation days, and birth weight of newborns were collected. The expression levels of free CD44 and CD69 in the peripheral blood  were detected by ELISA. The results showed that the levels of peripheral free CD44 and CD69 in the preeclampsia group were significantly lower than those of the control group (both P＜0.001). Multivariate Logistic regression analysis showed that, after controlling for potential confounding factors, CD44 and CD69 still showed independent impacts on the occurrence of preeclampsia (both P＜0.001). In addition, the levels of CD44 and CD69 significantly affected the severity of preeclampsia (all with P＜0.05). ROC curve analysis showed that the area under the curve (AUC) of either CD44 or CD69, and that of the combination of the two factors were all above 0.7, indicating their predictive value for preeclampsia, with combination of CD44 and CD69 being the best predictor (AUC=0.968, P＜0.001). In terms of neonatal outcomes, free CD44 and CD69 levels in peripheral blood during the first trimester were positively correlated with neonatal birth weight and gestation days (all with P＜0.05). In conclusion, the levels of free CD44 and CD69 in peripheral blood during early pregnancy can be used as a biomarker to predict the occurrence of preeclampsia, and may provide auxiliary information for evaluating the severity of preeclampsia and neonatal outcomes, as well as a reference for personalized clinical screening and prevention strategies.

IgA vasculitis (IgAV) is a common vasculitis syndrome during childhood and is considered a self-limiting disease. While its pathogenesis remains largely elusive. The short-term symptoms primarily involve skin, gastrointestinal tract and joint burden, with a generally favorable prognosis. However, in the long course, severe renal damage can progress to renal failure. Therefore, investigating the pathogenesis of IgAV is crucial for preventing the disease and managing related organ damage. Accumulating evidences indicate a strong correlation between galactose-deficient IgA1 (GD-IgA1) and the occurrence of IgAV. This review comprehensively discusses the relationship between GD-IgA1 and pediatric IgAV and  firstly  elucidates the central role of GD-IgA1 in IgAV pathogenesis from multiple dimensions, including genetics, immune cells, infection, and the gut microbiota. This review also elaborates the mechanisms underlying the formation and deposition of immune antibody complexes and their sequential damage to kidney and gastrointestinal tract which provide a theoretical foundation for deeper understanding of the disease pathogenesis and the development of glycosylation targeted and microbiome-based interventions.

The study aims to explore the role of E2F transcription factor 8 (E2F8) on glycolysis and tumor immunosuppression in breast cancer cells. Tissues from 12 breast cancer patients were collected and E2F8 expression was detected by immunohistochemistry and Western blotting. The E2F8 expressions of human breast cancer cell lines and the normal human breast epithelial cell line were measured by Western blotting. Stable E2F8- and serum amyloid A1 (SAA1)-overexpressing MCF-7 cell lines and negative control cell lines were constructed, as well as stable E2F8- and SAA1-knockdown T47D cell lines and negative control cell lines. Western blotting was used to detect the expressions of glycolysis-related proteins including lactate dehydrogenase A (LDHA), hexokinase 2 (HK2), and pyruvate kinase M2 (PKM2). qRT-PCR was employed to measure the protein levels of IL-6, TNF-α ，and C-X-C motif chemokine ligand 10 (CXCL10) mRNA in cells. THP-1 cells were differentiated into M0 macrophages by phorbol ester induction. M0 macrophages were co-cultured with E2F8-knockdown T47D cells and E2F8-overexpressing MCF-7 cells, and the M1/M2 polarization was analyzed by flow cytometry. The results showed that E2F8 expression was upregulated in tumor tissues as well as all tumor cell lines. In E2F8- and SAA1-overexpressing cells, the protein levels of SAA1, LDHA, HK2, and PKM2 were significantly increased, while the knockdown cells showed the opposite results. When co-cultures with E2F8-overexpressing cells, the proportion of M1 macrophages was significantly reduced (P<0.001), while M2 ratio was significantly increased (P<0.01). In contrast, the knockdown group showed the opposite results (P<0.05). In the E2F8-overexpressing group, IL-6, TNF-α, and CXCL10 mRNA levels were significantly decreased (P<0.01), while in the knockdown group, the opposite results were observed (P<0.01). This study suggests that E2F8 enhances glycolysis in breast cancer cells by promoting SAA1 protein expression and release.

The aim of the study was to investigate the effect of human umbilical cord blood mesenchymal stem cell (hUC-MSC) on immune thrombocytopenia (ITP) mouse model and its regulation on the retinoic acid-related orphan receptor γt (ROR-γt)/forkhead winged helix transcription factor 3 (Foxp3) signaling pathway. Healthy hUC-MSCs were isolated and cultured, the growth patterns were observed and identified, and the stably-proliferating primary cells were selected for passaging. Thirty male BALB/c mice were randomly divided into the normal control group (Con group), the ITP model group and the hUC-MSC group, with 10 mice in each group. After corresponding treatments, the general condition of the mice was observed. Peripheral platelet count (PLT) was measured, and serum levels of IL-6, IL-17, IL-10, and TGF-β1 were detected using ELISA. Wright-Giemsa staining was used to evaluate the pathological changes in mouse bone marrow and to count the megakaryocytes. Western blotting and RT-qPCR were used to detect protein and mRNA levels of ROR-γt and Foxp3 in mice spleen and peripheral blood, respectively. The results showed that compared to those of the Con group, the serum IL-6 and IL-17 levels, ROR-γt mRNA and protein expression in spleen and the ROR-γt mRNA and protein expression in peripheral blood were all significantly higher in the ITP model group (all with P＜0.05), while the PLT, serum IL-10 and TGF-β1 levels, Foxp3 mRNA and protein expression in spleen and Foxp3 mRNA and protein expression in peripheral blood were significantly decreased (all with P＜0.05), along with significantly reduced number of platelet-producing megakaryocytes (P＜0.05). Compared to the ITP model group, the hUC-MSC group showed significantly lower serum IL-6 and IL-17 levels, splenic ROR-γt mRNA and protein expression and peripheral blood ROR-γt mRNA and protein levels (all with P＜0.05), but significantly higher PLT, serum IL-10 and TGF-β1 levels, splenic Foxp3 mRNA and protein expression, peripheral blood Foxp3 mRNA and protein expression (all with P＜0.05), and the elevated number of platelet-producing megakaryocytes (P＜0.05). As a result, hUC-MSC can promote platelet formation and increase the number of platelet-producing megakaryocyte, which may relief the symptoms of ITP mice by regulating the expressions of cytokines and the ROR-γt/Foxp3 axis.

This study aims to explore the effect of Qianjin Weijing Decoction on acute lung injury in sepsis rats through pyroptosis mediated by NF-κB/NOD-like receptor family pyrin domain-containing protein 3(NLRP3) signaling pathway. Rat model of sepsis was established by cecal ligation. Rats were randomly divided into the model group, the low-dose, medium-dose and high-dose Qianjin Weijing Decoction groups, and the Qianjin Weijian Decoction + phorbol 12-myristate 13-acetate (PMA; NF-κB signaling pathway activator) group, with 12 rats in each group. An other 12 rats from the same cohort without cecal ligation were assigned as the sham operation group. The lung index and water content of lung tissue were measured. The pathological changes of lung tissue were observed by H-E staining, and the relevant scoring was calculated. The pyroptosis of lung tissue was detected by immunofluorescence staining. The levels of inflammatory factors in serum were detected by ELISA. The expressions of NF-κB/NLRP3 signaling pathway related proteins were detected by Western blotting. The results showed that compared to those of the sham operation group, the lung index, water content of lung tissue, score of lung injury, relative fluorescence intensity of NLRP3, levels of serum IL-1β, IL-18, and TNF-α, expressions of phosphorylated NF-κB p65 (p-NF-κB p65)/NF-κB p65, NLRP3 and cleaved Caspase -1 (C-Caspase-1) protein in lung tissue were all increased in the model group (P<0.05). Compared to those of the model group, the lung index, water content of lung tissue, score of lung injury, relative fluorescence intensity of NLRP3, levels of serum IL-1β, IL-18, and TNF-α, expressions of p-NF-κB p65/NF-κB p65, NLRP3 and C-Caspase-1 in lung tissue were all decreased in the medium-dose and high-dose Qianjin Weijing Decoction groups (P<0.05). The treatment of PMA reversed the above effects of Qianjin Weijing Decoction. This study shows that Qianjin Weijing Decoction may inhibit pyroptosis by down-regulating the NF-κB/NLRP3 signaling pathway, thus alleviate acute lung injury in sepsis rats.

The aim of the study is to investigate the effects of icariin on apoptosis of retinal cells in diabetic retinopathy (DR) rats through the silent mating-type information regulation 2 homolog 1 (SIRT1)/forkhead-box transcription factor O3a (FOXO3a)/NF-κB signaling pathway. The SD rats were randomly divided into the control (Ctrl), the DR, the low-dose icariin (L-icariin), the high-dose icariin (H-icariin), and the SIRT1 inhibitor + H-icariin groups. The DR rat model was established by intraperitoneal injection of streptozotocin (STZ) combined with high-sugar+high-fat diet. Serum levels of oxidative stress markers (superoxide dismutase ［SOD］ and malondialdehyde ［MDA］), and inflammatory factors (TNF-α and IL-6) were measured. Retinal histopathological changes were observed by H-E staining. Retinal cell apoptosis was assessed by TUNEL assay. B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) expressions were detected by immunohistochemistry. Western blotting was used to analyze the protein expressions of SIRT1 and acetylated NF-κB (ac-NF-κB). Immunoprecipitation (IP) was used to detect ac-FOXO3a protein expression in retinal tissue. The results showed that compared with the Ctrl group, the DR group exhibited reduced serum SOD level and increased expressions of MDA, TNF-α, and IL-6 (all with P＜0.05). Retinal cells displayed disordered arrangement and were significantly decreased in number, accompanied by cellular edema and nuclear shrinkage. The apoptosis rate of retinal cells was increased (P＜0.05), along with decreased Bcl-2 and increased Bax protein expressions in retinal tissue (all with P＜0.05). After intervention with L-icariin or H-icariin, these abnormalities were mitigated, with the H-icariin group showing better efficacy. Compared with the Ctrl group, the DR group demonstrated reduced SIRT1 protein expression and increased ac-FOXO3a and ac-NF-κB protein expressions (all with P＜0.05) in retinal tissue. Both H-icariin intervention and concurrent SIRT1 inhibitor treatment diminished or reversed these protein expression profiles. Notably, SIRT1 inhibitor reduced the effect of icariin on retinal cell apoptosis. These findings suggest that icariin may alleviate retinal lesions and inhibit retinal cell apoptosis in DR rats through regulating the SIRT1/FOXO3a/NF-κB signaling pathway.

This study aimed to investigate the role of tripterygium glycosides (TG) in alleviating the pathological damage and inflammation in the colonic tissue of ulcerative colitis (UC) mice. A total of 60 BALB/C mice were randomly divided into 4 groups: the control group, the model group, the low-dose TG group, and the high-dose TG group, with 15 mice in each group. All groups, except the control group, were treated with 3% dextran sulfate sodium (DSS) solution for 7 consecutive days to induce the UC model. The treatment groups received TG by oral gavaging for 7 days, during which body weight, fecal condition, and disease activity index (DAI) were monitored. After the treatment, colonic tissue pathology was assessed using H-E and periodic acid-Schiff (PAS) stainings, and levels of serum inflammatory cytokines were measured by ELISA. Western blotting was used to detect the protein expressions of tight junction protein 1 (ZO-1), occludin, NOD-like receptor family pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), Caspase-1, IL-1β, and IL-18 in the colon tissue. The results showed that TG treatment significantly reduced the DAI score (P<0.05), promoted the recovery of colonic length (P<0.01), and alleviated inflammatory damage in colonic tissue. Serum levels of TNF-α, IL-1β, and IL-6 were significantly reduced, while the level of IL-10 elevated (P<0.05). Furthermore, TG treatment significantly decreased the protein expressions of NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in colonic tissue (P<0.05) while increased the expressions of ZO-1 and occludin (P<0.05). In conclusion, TG may alleviate symptoms of UC mice by modulating the NLRP3/Caspase-1 signaling pathway to inhibit inflammation and restore intestinal barrier function.

As an important part of the innate immune system, immune responses of macrophages are triggered by PAMP recognized by PRR, which have important functions in host defense and maintenance of tissue homeostasis. Bacterial infection can induce macrophage death through a variety of pathways, including apoptosis, pyroptosis, necroptosis, and ferroptosis, which affect the host immune response and disease process. Different types of cell death have different effects on host immune response and bacterial clearance. Bacteria can evade immune clearance by regulating macrophage death, leading to chronic or systemic infections. This review focuses on different mechanisms by which bacterial infection regulates macrophage death and its impact on the host immune response. Future studies on the molecular mechanisms of macrophage death under different bacterial infection conditions and their regulation of the host immune response may help to develop new therapeutic strategies, such as targeted drugs or cell therapies, to deal with the challenges of drug-resistant bacteria and systemic infections.

The study aimed to explore the regulation of N6-methyladenosine (m6A) modification of SOCS2 on the progression of colorectal cancer via the JAK2/STAT3 signaling pathway and the possible underlying mechanism. Human normal colon epithelial cell NCM460 and human colon cancer cells SW480, LOVO, HCT-15, HT-29, and SW1116 were cultured, and the overall level of m6A RNA was detected. Western blotting and RT-qPCR were used to detect METTL3 protein and mRNA levels, respectively, and SELECT-qPCR modified quantitative technique was used to detect the m6A level at SOCS2 site. LOVO and HT-29 cells were divided into the control group (WT cells) and the METTL3 low expression group (transfection with low-expression METTL3 plasmid). SOCS2 levels in LOVO and HT-29 cells were detected by immunofluorescence staining. Western blotting was used to detect the expression levels of JAK2, STAT3, p-JAK2 and p-STAT3 in LOVO and HT-29 cells. Plate clone formation assay was used to detect the clone-forming ability of LOVO and HT-29 cells, and scratch assay was used to detect the migration of LOVO and HT-29 cells. The invasive ability of LOVO and HT-29 cells was detected by the Transwell assay. The results showed that, compared to those of NCM460, the overall levels of m6A RNA in all the cancer cell lines were increased (P<0.05, P<0.01), and the protein and mRNA levels of METTL3 in LOVO and HT-29 cells were also increased (P<0.01). The m6A level of SOCS2 was increased (P<0.05). Compared to that of the control group, the expression of SOCS2 in LOVO and HT-29 cells in the METTL3 low expression groups were increased (P<0.01), while the expression of METTL3 protein and mRNA were decreased (P<0.01), and no significant changes in JAK2 and STAT3 (P>0.05) were observed. The expressions of p-JAK2 and p-STAT3 were decreased (P<0.01), and the proliferation, migration, and invasion abilities of LOVO and HT-29 cells were also decreased (P<0.01). This study indicates that low expression of METTL3 can downregulate JAK2/STAT3 signaling pathway and inhibit the proliferation, migration, and invasion of colon cancer cells, which may be related to the regulation of JAK2/STAT3 signaling pathway by m6A modification of SOCS2.

The study aims to analyze the expressions of non-structural maintenance of chromosome condensin Ⅰ complex subunit D2 (NCAPD2) and a disintegrin and metalloprotease 17 (ADAM17) in colon cancer tissues and the correlation with patient prognosis. One hundred colon cancer patients subjected to radical resection surgery were selected. During the surgery, colon cancer tissue specimens and normal tumor-adjacent tissue specimens with a distance of more than 5 cm from the colon cancer tissue were collected from the patients. The expression levels of NCAPD2 and ADAM17 in the two types of specimens were detected by Western blotting, and the expressions of NCAPD2 and ADAM17 in patients with different clinical and pathological characteristics were analyzed. The patients were followed up for 3 years and their survival data were recorded. The pateints were divided into the survival group (67 cases) and the death group (33 cases). The expression levels of NCAPD2 and ADAM17 were compared between the two groups. ROC curve was used to evaluate the predictive value of NCAPD2 and ADAM17 for the prognosis of colon cancer patients. The cut-off value in the curve was used as the threshhold for NCAPD2 and ADAM17 expressions, which was used to divide patients into high expression and low expression groups. Meanwhile, Kaplan-Meier survival curve was used to compare the survival of the two groups. The results showed that the expression levels of NCAPD2 and ADAM17 in colon cancer tissues were higher than those in normal tissues (P<0.001). The expression levels of NCAPD2 and ADAM17 in patients with infiltration degree T3-T4, low differentiation, distal metastasis, and lymph node metastasis were higher than those in the corresponding control group (P<0.05). The expression levels of NCAPD2 and ADAM17 in the death group were higher than those in the survival group (P<0.05). The ROC curve showed that the AUC of NCAPD2 and ADAM17 for predicting death were 0.780 and 0.721, respectively. The Kaplan-Meier survival curve showed that the survival time of patients with high expressions of NCAPD2 and ADAM17 was significantly shorter than that of patients with low NCAPD2 and ADAM17 expressions (P<0.001). The study suggests that NCAPD2 and ADAM17 are highly expressed in colon cancer tissues, and are highly correlated to the invasion, metastasis and prognosis of colon cancer, underscoring their significance in the prognosis assessment of colon cancer patients.

Anti-cytokine autoantibodies (ACAA) exist in various infectious and immune-related diseases, and have gained increasing attention in refractory infectious diseases in recent years. The titer of neutralizing autoantibodies is closely related to the severity and prognosis of infectious diseases. Patients with high titers of antibodies often have more severe clinical symptoms, less satisfactory anti-infective benefits, higher risk of recurrence, and worse prognosis. The correlation between ACAA and clinical phenotypes reveals new mechanisms of complex opportunistic and refractory infections, which provide new treatment strategies for diseases. This review focuses on ACAA related infectious diseases, describing different clinical phenotypes, introducing current treatment measures, and finally proposing the clinical and basic research directions of infection immunity in the future.