This study aims to develop a method to efficiently and stably induce the differentiation and expansion of human myeloid-derived suppressor cells (MDSC) in vitro and provide new experimental technology for the study of the function and mechanism of human MDSC. For this purpose, PBMC of healthy volunteers were isolated with Ficoll density gradient centrifugation. Next, monocytes were separated by anchoring technique. PBMC or monocytes were stimulated with GM-CSF and IL-6 (10, 20, 40, 80 ng/mL each) for 4, 7, 14, and 21 days before co-culturing with PBMC for 3 days. The proliferation of CD33⁺ MDSC and T cells and the proportion of CD3⁺IFN-γ⁺ T cells were detected by FACS. The results showed that the PBMC or monocytes were induced to differentiate to less CD33⁺MDSC by conventional methods. However, by improved methods, the monocytes cultured with GM-CSF and IL-6 (each 80 ng/mL) for 14 days (refreshing the culture solution every 4-5 days) were induced to differentiate more efficiently into a higher proportion of CD33⁺MDSC, which showed significant inhibition of T cell proliferation and IFN-γ secretion. This study suggests that with the improved method, the monocytes are efficiently induced to differentiate into CD33⁺ MDSC, which has significant suppressive function.

Interferon regulatory factor 4 (IRF4) is an evolutionarily conserved regulatory molecule that is expressed in varying levels at key stages of differentiation of many immune cells. In terms of its role in the differentiation of innate immune cell lineages, IRF4 is one of the key transcription factors regulating M2-like macrophage polarization and differentiation of both monocyte-derived DC and conventional DC 2 (cDC2). On the other hand, on the differentiation and fate determination of adaptive immune cell subgroups, IRF4 plays a broad role and controls all levels of differentiation of these immune cell subgroups in that IRF4 regulates the differentiation of the naive CD4⁺ T cells into various subsets (Th1, Th2, Th9, Th17, Treg, and follicular helper T cell ［Tfh］). In addition, it also dictates the differentiation of naive CD8⁺ T cells into effector cells. At the same time, IRF4 also regulates B cell differentiation cycle and plasma cell function, thereby affecting humoral immunity. The recent progress in the study of IRF4's involvement in the regulation of immune cell lineage differentiation and fate determination is summarized in this review.

During the global pandemic of COVID-19, memory T cells have drawn increasing research attention because of their superior antiviral capacity. The latest research demonstrates that certain APC and cytokines in the microenvironment are required for the differentiation and effector responses of memory CD4⁺ T cells via tightly modulated intracellular transcription factors and energy metabolism. This review summarizes and discusses the key mechanisms underlying the development, long-term maintenance, and secondary immune responses of memory CD4⁺ T cells. Precise regulation of their number and functions in different types of diseases will be a big challenge in the future.

 Neutrophils are one of the most important effector cells in innate immunity and the defense at the frontline against invading pathogens. With the continuous advances, people have realized that neutrophils not only participate in the inflammatory response and tissue damage repair, tumor-associated neutrophils also act as anti- or pro-tumorigenic factors depending on specific tumor microenvironment (TME) status. Neutrophils with different functions may have different phenotypes and also some plasticity. This review begins with the biological properties of neutrophils, and then summarizes the diverse phenotypes of neutrophils with different functions in the TME, the possible mechanisms of immunosuppressive neutrophils regulating tumor immunity, and the clinical application of neutrophils in cancer research.

Corona virus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global health emergency. Adaptive immune response plays a critical role in clearing virus-infected host cells, mainly relying on T cells. The structure of the T cell receptor (TCR) determines the specificity of viral antigen cluster recognition, and the characteristics of the TCR complementarity determining region 3 (CDR3) repertoire of infected individuals have indications  for the occurrence and development of COVID-19 disease. Additionally, human leukocyte antigen (HLA) gene is the main factor responsible for individual varieties in immune responses to antigens and plays an important role in human immune responses. This review focuses on the research progress and overview of the relationships of TCR CDR3 repertoire characteristics and of the composition of host HLA alleles with COVID-19.

Receptor for advanced glycation end products (RAGE), a type of membrane protein, is a member of the immunoglobulin superfamily. Over the past ten years, hundreds of papers have described the correlation between RAGE and the pathophysiological status and prognosis of lung diseases including severe pneumonia, asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and lung carcinoma. However, many findings were inconsistent. This review summarizes the origin and biological function of RAGE. It also discusses the acting mechanism of RAGE in lung diseases and the therapeutic effect of traditional Chinese medicine via RAGE regulation, aiming to provide new ideas and strategies for improving related lung diseases.

More and more studies have shown that the occurrence of atherosclerosis is closely related to pyroptosis, especially gasdermin D（GSDMD）-mediated pyroptosis. In atherosclerosis, inflammatory cells such as macrophages, vascular endothelial cells, and vascular smooth muscle cells undergo pyroptosis, leading to plaque rupture and thrombosis, and finally to acute coronary syndrome. In the development of atherosclerosis, arterial wall endothelial injury and lipid deposition are the main initiating factors, which activate Caspase-1 and Caspase-11/4/5, respectively, and in turn cause the cleavage of the GSDMD protein and mediate classical and non-classical cell pyroptosis. The N-terminus of the GSDMD protein migrates to the cell membrane and oligomerizes to form pores through which the inflammatory factors IL-1β and IL-18 are released into the interstitium. The release of inflammatory factors further promotes the death of intravascular cells, after which their contents, cytokines, and proteases enter the extracellular matrix, aggravating the local inflammatory response, leading to atherosclerotic plaque rupture and cardiovascular disease. Based on the above mechanism, the development of drugs that directly target GSDMD and signal molecules in the pyroptosis signaling pathway induced by GSDMD, such as inflammasomes, Caspase-1, IL-1β, and IL-18, provides a theoretical basis and new ideas for the treatment of atherosclerosis.

NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome is a protein complex that stimulates the activation of caspase and the maturation of IL-1β, and promotes the pathogenesis and development of various inflammations. The occurrence of periodontitis (PD) is related to the dysbacteriosis of periodontal tissue. NLRP3 inflammasomes are involved in the activation of neutrophil, macrophage, osteoclast (OC), and human periodontal ligament fibroblast (HPLF). This review summarizes the effects of NLRP3 inflammasome in the related immune and stromal cells on PD, and outlines new ideas for PD treatment targeting NLRP3 inflammasome.

Immunotherapy has become one of the main modalities for tumor treatment. CTLA-4 and PD-1 are the two main players in tumor immune escape. However, the low response rate of PD-1 and CTLA-4 treatments is the main challenge facing tumor immunotherapy at present. Lymphocyte activation gene 3 (LAG-3), a new-generation inhibitory immune checkpoint, plays an important regulatory role in the human immune system. LAG-3 is highly expressed on various types of TIL and mediates tumor immune escape through multiple mechanisms. LAG-3 can also be co-expressed with PD-1 in TIL. Combined blockade of LAG-3 and PD-1 synergistically inhibits immune escape, increases antitumor response, and enhances T cell proliferation. It has become one of the most promising immunotherapies to improve the current deficiencies in tumor immunotherapy. Therefore, it is of great significance to deeply understand the biological characteristics of LAG-3 and further explore its mechanism of action. In addition, the structure and function of LAG-3 as well as its research progress in tumor immunity are reviewed.

Sialoadhesin, also known as CD169, is an adhesion and endocytic receptor of macrophages that can recognize sialic acid. CD169 is a highly conservative molecule in evolution. Under physiological conditions, CD169 is expressed on the surface of macrophage subpopulations in secondary lymphoid tissues. Several studies have demonstrated that CD169⁺ macrophages can phagocytize pathogens by interacting with α2,3- and α2,6-sialic proteins, and can also coordinate with DC to cross-present antigens to T cells. Moreover, CD169 can exert an immunosuppression role by inhibiting the expression of type Ⅰ IFN in macrophages. Recently, the roles of CD169⁺ macrophages in various pathological conditions have been reported. It has been shown that when erythropoiesis is under stress, CD169⁺ macrophages can bind to CD43 of erythroblast and affect erythroblast differentiation. In addition, CD169 has been reported to play a dual role during pathogen infection or tumor progression. This review will focus on the advance progress of CD169 and the function of CD169⁺ macrophage, as well as its role in various diseases including virus infection, tumor development, and hematological diseases.

B cells are the major component in the tumor microenvironment and play key roles in tumor immunity. Previous studies have suggested that B cells promote tumor progression via secreting immune-inhibitory cytokines or activating the complement system through  B cell-secreted antibodies. However, recent studies have revealed an important role of B cells in anti-tumor immune responses. This review summarizes the multiple functions of B cells in tumor immunity and discusses the underlying mechanisms and the effects on patients prognosis. 

Medulloblastoma (MB) is the most common pediatric brain malignancy, with a 5-year overall survival (OS) rate of around 70%. In recent years, the role of the tumor microenvironment on tumor growth has attracted extensive attention. The interaction between tumor cells and other cells in the tumor microenvironment including tumor-associated macrophages (TAM), T cells, NK cells, B cells, and tumor-associated astrocytes (TAA) plays an important role in the onset and progression of MB. Understanding the tumor immune microenvironment of this tumor, especially the relationship between tumor and immune cells, is crucial for the effective development of immune-based therapeutic strategies for MB. This review summarizes the latest research progress on the tumor microenvironment and immunotherapy of MB.

The goal of this study is to elucidate the mechanism by which inflammatory pain regulated mitochondrial function and apoptosis of macrophages via down-regulation of miR-34a and up-regulation of X-inactive specific transcript (XIST). For this purpose, the expressions of XIST were measured in miR-34a over-expressed or LPS-treated J774A.1 (female mouse cell line) and the SH-SY5Y (female human cell line) cells; And the in vivo correlation between the expressions of miR-34a and XIST  was also analyzed. MitoTracker and TMRE (tetramethylrhodamine ethyl ester) staining were used to analyze the mitochondrial volume and membrane potential in J774A.1 cell line. The mitochondrial stress assay (Seahorse) was conducted to test the mitochondrial function in J774A.1 cells after over-expressing miR-34a and/or stimulated with LPS. TUNEL assay was used to assess cell line apoptosis. CFA (complete Freund's adjuvant)-induced acute inflammatory pain model was established to detect the pain reaction threshold and the expression of XIST and miR-34a in acute and chronic phases and healthy controls, respectively. Real-time PCR was used to detect the expression of XIST in the blood of complex regional pain syndrome (CRPS) patients and healthy controls. The results showed that there was no significant difference in XIST expression between the control group and the CRPS group in total human samples (t=1.528, P=0.131). And there was no statistical difference between the two groups (t=0.945, P=0.353) when only male patients were analyzed. However, in female patients, the XIST expression of the CRPS group was significantly higher than that of the control group (t=2.764, P=0.008). Over-expression of miR-34a reduced XIST expression in J774A.1 and SH-SY5Y cells. The datum from patients showed that the expression of miR-34a and XIST exhibited a negative correlation (r2=0.681, P＜0.001). LPS treatment inhibited the expression of miR-34a and up-regulated XIST expression in J774A.1 cell line. In mouse pain model, XIST expression was up-regulated (t=1.810, P＜0.001) and miR-34a expression was down-regulated (t=2.220, P＜0.001) at 4 h time point, and the difference disappeared at D14. LPS up-regulated mitochondrial volume and membrane potential, while over-expression of miR-34a led to down-regulation of both. And the effects of the two treatments compensated for each other. LPS stimulation significantly decreased cellular oxygen consumption (t=4.323, P=0.014), ATP production (t=4.323, P=0.014) and the maximum oxygen consumption (t=1.885, P=0.008), while miR-34a over-expression had the opposite effect （t=4.245, P=0.004）. LPS reduced cell apoptosis whereas miR-34a over-expression promoted it. XIST over-expression can reverse the cell apoptosis mediated by miR-34. In conclusion, inflammation may promote the expression of XIST by down-regulating miR-34a and the former suppresses cell apoptosis by promoting the maintenance of mitochondrial function.

The aim of this study is to investigate the immuno-modulatory effect of IL-17A preconditioned (ameliorated) adipose-derived mesenchymal stem cells (ADSCs）on peripheral blood lymphocytes and to explore the underlying mechanism.  Subcutaneous adipose tissue was collected from four abdominal surgery patients consulting Tianjin People's Hospital, along with the peripheral blood. ADSCs  were isolated, cultured and identified. Next, ADSCs were divided into two groups preconditioned with or without IL-17A (named ADSC-17 group and ADSC group, respectively), which were co-cultured with phytohemagglutinin (PHA)+IL-2-stimulated lymphocytes. The proliferation inhibitory rate of activated lymphocytes was analyzed by MTT assay. The percentage of CD4⁺CD25⁺ T lymphocytes was detected by FACS. ELISA was performed to detect the TGF-β1 level in culture supernatants. The results revealed that after in vitro culturing, both ADSC and ADSC-17 groups strongly expressed cluster of differentiation (CD)90, CD105, and CD73 as well as displayed osteogenic and adipogenic potentials. The ADSC-17 group showed significantly enhanced proliferation inhibitory rate of activated lymphocytes in a dose-dependent manner compared to that of the ADSC group (all with P＜0.01). The percentage of CD4⁺CD25⁺ T lymphocytes and the secretion of TGF-β1 in ADSC-17 group were significantly increased (both P＜0.05) compared to those of the ADSC group. Altogether, the preconditioning of ADSCs by IL-17A can augment the capacity of ADSC to inhibit lymphocyte proliferation and to induce CD4⁺CD25⁺ T lymphocyte  differentiation so as to become an effective strategy for inducing lymphocytes hypo-responsiveness.

Signet ring cell carcinoma (SRCC) is a rare but distinctive pathological subtype of colorectal cancer (CRC) with a mucin-rich phenotype as well as high metastatic rate and poor prognosis. In our large cohort of single-cell RNA sequencing (scRNA-seq) study of CRC, one case of SRCC was serendipitously enrolled. It is currently the first scRNA-seq data of SRCC derived from CRC in the world. Using this batch of scRNA-seq data including the SRCC, we aimed to compare the SRCC case with common adenocarcinoma (AC) in order to elucidate the cellular and molecular mechanisms behind SRCC. The results suggested that goblet-like malignant cells in SRCC contributed to its unique phenotypes. These cells specifically upregulated protein processing and cell adhesion related signaling pathways and overexpressed multiple mucin genes. Epithelial to mesenchymal transition (EMT) was associated with CRC metastasis. SRCC exhibited high level of EMT, in accordance with its high malignancy. However, the EMT related genes in SRCC were different from those of common AC. The potential prognostic role of genes related to EMT was revealed by combining the transcriptomic data and follow-up information of CRC in The Cancer Genome Atlas (TCGA) database. Compared to AC, SRCC had a smaller proportion of lymphocytes and a larger proportion of myeloid cells, and the correlation between epithelial and immune cells was reduced. Collagen and integrins interacted extensively between epithelial cells and stromal cells in CRC. This study is the first to characterize colorectal SRCC at the single cell level which is a powerful complement to the single-cell atlas of CRC, and provides new insights into the therapeutic targets of colorectal SRCC. 

To investigate the effect of  CD47 knockdown on the migration, proliferation, and chemokine secretion of ovarian cancer cells, small interfering RNA (siRNA) targeting CD47 was transfected to ovarian cancer cells and the knockdown efficiency was confirmed by Western blotting, qRT-PCR, and flow cytometry. Cell proliferation, migration, and invasion were examined using CCK-8, wound healing assay, and the Transwell assay, respectively. qRT-PCR was used to detect the expressions of CD47, C-X-C motif chemokine ligand 1（CXCL1）, CXCL8, C-C motif chemokine ligand 20（CCL20）and IL-6. ELISA was used to determine the release of IL-6 and CXCL8. Transwell was employed to study macrophage invasion of CD47 knockdown ovarian cancer cells. The results showed that the expressions of chemokines CXCL1, CXCL3, CXCL8, CCL20, and IL-6 in ovarian cancer cells were reduced when CD47 was knocked down, along with the reduction of the migration capacity of macrophages towards ovarian cancer cells. CD47 knockdown did not affect the proliferation, migration, or invasion of ovarian cancer cells. Our findings suggest that CD47 in ovarian cancer cells can affect the migration ability of macrophages by regulating their chemokine expression.

TNF-α is a pro-inflammatory Th1-type cytokine secreted by immune and placental cells, which plays important roles in regulating the inflammatory and immune mechanisms of embryo implantation, placentation，and final pregnancy outcome. Moderate increase of TNF-α in early pregnancy may be beneficial to embryo implantation. However, over-expression of TNF-α can lead to the occurrence of reproductive immune diseases through different pathways, and cause unexpected pregnancy and birth outcomes. In recent years, the clinical application of TNF-α in reproductive immune diseases has become a hotspot in reproductive medicine. Nonetheless, questions on whether TNF-α can be used as a routine screening target for reproductive immune diseases, whether TNF-α antagonists can improve pregnancy outcomes, or whether short-term/long-term use of TNF-α is safe for mother and fetus are required to be carefully considered. Based on above questions, this review discusses the value of TNF-α and its antagonists on the diagnosis and treatment of reproductive immune diseases, for providing new ideas to develop clinical diagnosis and treatment strategies.

Protein kinase CK2 is a highly conserved and ubiquitous protein kinase which phosphorylates a variety of protein substrates, and is involved in the regulation of several signaling pathways. Abnormal CK2 expression can lead to dysregulation of various signaling pathways, which is closely related to tumorigenesis and progression. This review summarizes the composition, structure and regulatory role of CK2 in important tumor-related signaling pathways and provides foundation to further explore CK2-targeted therapeutic strategies in cancer.

Gut microbiota dysbiosis exists in patients with different types of cancer, including melanoma, breast cancer, brain glioma, and other parenteral solid tumors. Dysregulated gut microbiota induces the formation of immunosuppressive tumor microenvironment through a variety of mechanisms, causes the occurrence of tumor immune escape, and affects the host's responses to immune checkpoint inhibitors (ICI). The regulatory effects of gut microbiota can enhance the function of immune killer cells and inhibit tumor progression. This review summarizes the regulatory effect of gut microbiota on the progression of parenteral solid tumors and the underlying immunological mechanisms, so as to provide insights for further basic research and clinical application. 

The purpose of this study was to investigate the changes in postoperative plasma IL-10 levels in allogeneic lung transplant recipients and its relationship with death due to bacterial infection. To this end, plasma samples were collected from healthy volunteers and lung transplantation recipients who  either deceased, survived or lived with a good long-term prognosis. For the deceased group, the immune cell distributions in peripheral blood were analyzed by routine blood analysis. The pathogenic infection status was examined by imaging and the type of pathogenic infection was analyzed by in vitro  bacteria culture and by high-throughput genomic sequencing of pathogenic microorganisms. In addition, the concentration of multiple cytokines in all plasma samples was monitored by Luminex multifactor detection. The results showed that in the deceased recipients, postoperative white blood cell count (WBC), absolute neutrophil count (NEUT) and percentage (NEUT%), CRP concentration, and neutrophil-lymphocyte ratio (NLR) were all increased, while red blood cell count (RBC) and platelet count (PLT) were decreased. Moreover, some high-density shadows were observed in the postoperative lungs along with multiple bacterial infections in the blood, bronchoalveolar lavage fluid (BALF), and sputum. Dynamic monitoring of cytokines concentration showed that plasma IL-10 concentration and IL-10/IFN-γ ratio were all significantly increased (all  P＜0.000 1) in the deceased recipients after allogeneic lung transplantation compared to those of survived recipients, recipients with good prognosis and healthy volunteers. Altogether, this work suggests, for the first time, that the change in plasma IL-10 level is highly related with increased bacterial infection and mortality  in lung transplantation recipients.

Natural killer cell receptor group Ⅱ member A (NKG2A) is an inhibitory receptor of the NKG2 receptor family, which is mainly expressed on a variety of immune cells represented by NK cells. Studies have also revealed that NKG2A is involved in the development of a variety of tumors. NKG2A targeting drugs are currently in clinical phase trials for multiple epithelial tumors. The review describes the biological properties of NKG2A and its regulatory role on CD8⁺ T cells, NK cells, and other immune cells. The review further explores the mechanism of NKG2A as an immune checkpoint in anti-tumor immunity, and provides a theoretical basis for clinical anti-tumor immunotherapy.

The poliovirus receptor (PVR) gene is closely related to tumorogenesis and development, while the regulatory roles and mechanisms of PVR in tumor immunity are not fully elucidated. This study analyzed the expression of PVR in different types of tumor tissues from a pan-cancer perspective and its correlation with patients prognosis and immunity. The analysis of the expression differences of PVR between cancerous and normal tissues was based on The Cancer Genome Atlas (TCGA) and TIMER database, and the correlation between PVR and the prognosis of cancer patients was assessed using survival analysis tools. Expression analyses of PVR in various with immune cells infiltration, immune checkpoint (ICP) genes expression and stromal/immune scoring were evaluated by the TIMER database and R software. To further understand the potential biological mechanisms of PVR  in various cancers, single-cell level sequencing and Gene Set Enrichment Analysis (GSEA)  were performed. The expression of PVR was verified by qRT-PCR in a variety of cancer cell lines. The results showed that, compared to that of normal tissues, PVR was significantly differentially expressed in tumor tissues like bladder urothelial carcinoma, cholangiocarcinoma, colon adenocarcinoma, esophageal carcinoma, and head & neck squamous cell carcinoma, etc. Aberrant expression of PVR was associated with poor prognosis for multiple cancers including adrenocortical cancer, bladder urothelial carcinoma, breast invasive carcinoma, and cervical carcinoma, etc. PVR expression was significantly correlated with immune cells infiltration, stromal/immune scoring and the regulation of ICP genes expression on pan-cancer level (all with P＜0.05). Single-cell sequencing outcomes showed that PVR was associated with tumor cells multiple cytobiological functions and phenotypes, including cell differentiation, gene silencing and DNA repairing. GSEA revealed that PVR was engaged in immune-related functions and signaling pathways in multiple tumor cells. The qRT-PCR results showed that PVR was highly expressed in stomach, colon and hepatocellular carcinoma cell lines compared to healthy cells. This comprehensive pan-cancer analysis suggests that PVR is an oncogene highly expressed in tumor tissues and leads to poor prognosis. Therefore, PVR may be a new immune-dependent prognosis-predicting marker that may provide new directions for targeted oncotherapy.

To investigate the effect and mechanism of paeoniflorin (PF) on human bronchial epithelial cells (BEAS-2B), THP-1 cells were induced to differentiate into macrophages by phorbol 12-myristate 13-acetate, and the toxicity of PF to THP-1 macrophages was detected by CCK-8 assay. THP-1 macrophages were cultured with 1 μg/mL LPS to induce inflammation, and treated with 1, 10, and 30 μmol/L PF for 24, 48, and 72 h, respectively. Cell viability was detected by CCK-8 assay, and the optimal concentration and treating time of PF were determined. BEAS-2B cells were inoculated in the upper chamber of Transwell and THP-1 macrophages were inoculated in the lower chamber of Transwell. THP-1 macrophages were divided into 4 groups: control group, LPS group, PF group, and LPS+PF group. The survival rate of BEAS-2B cells was detected by CCK-8 assay, the apoptosis rate of BEAS-2B cells was detected by FACS, the levels of inflammatory cytokines IFN-γ, IL-4, IL-17C, and IL-10 were detected by ELISA, and the expression levels of CD63, CD9, and apoptosis-linked gene 2-interaction protein X (Alix)  were detected by Western blotting. The expressions of M1 and M2 markers CD80 and CD206 in THP-1 macro-phages were detected by FACS. The results showed that the optimal concentration and treating time of PF were 10 μmol/L and 48 h. Compared to those in the control group, the cell survival rate, IL-4 and IL-10 levels and the proportion of M2-type macrophages in the LPS group were significantly decreased (P<0.01). On the other hand, the apoptosis rate, IFN-γ and IL-17C levels, CD63, CD9, Alix protein expression levels and the proportion of M1-type macrophages were significantly increased (P<0.01). Compared to those in the LPS group, the cell survival rate, IL-4 and IL-10 levels and the proportion of M2-type macrophages in the LPS+PF group were significantly increased (P<0.01), while the apoptosis rate, IFN-γ and IL-17C levels, CD63, CD9, Alix protein expression levels and the proportion of M1-type macrophages were significantly decreased (P<0.01). These results suggest that PF can improve the survival rate of BEAS-2B cells, reduce apoptosis, and inhibit exosome secretion and inflammatory response. The underlying mechanism may be related to PF induced M2-type polarization of macrophages.

To explore the effect and mechanism of Annexin A1 (ANXA1) peptidomimetic Ac2-26 on hemodynamics and myocardial mitochondrial damage in the acute heart failure (AHF) model, rats were divided into control group, model group, and Ac2-26 group (fifteen rats per group). AHF model was established in the model group and Ac2-26 group. Rats in Ac2-26 group were also intravenously injected with Ac2-26 once a day for fourteen days, whereas the control group and model group were treated with the same volume of saline. Color doppler ultrasound was used to detect the hemodynamic indexes. H-E staining was used to evaluate the pathological damage of myocardial tissue. TUNEL staining was used to detect the apoptosis of cardiomyocytes. Transmission electron microscope (TEM) was used to observe the mitochondrial structure. Changes in mitochondrial membrane potential were also evaluated. Macrophage marker CD68, M1 marker iNOS, and M2 marker CD206 were detected by immunohistochemistry. mRNA expressions of TNF-α, IL-6, TGF-β, IL-10 and recombinant human Arginase 1 (Arg-1) and protein expression levels of IL-10, Arg-1 and CD206 were evaluated by qRT-PCR and Western blotting, respectively. Compared with the model group, the left ventricular systolic pressure （LVSP）and maximum increase rate of left ventricular pressure (+LV dp/dtmax) of  rats in the Ac2-26 group were increased, left ventricular end-diastolic pressure （LVEDP）and maximum decrease rate of left ventricular pressure (－LV dp/dtmax) were decreased, and heart rate (HR) was increased; The number of cardiomyocytes in the myocardial tissue was large, and the inter-cellular space was narrowed, and the infiltration of inflammatory cells and macrophages was also  relieved; The positive rate of TUNEL staining was decreased, the damage of myocardial mitochondria was relieved, the structure was relatively intact, and the mitochondrial membrane potential was increased; The positive expression of iNOS in myocardial tissue was decreased, and the positive expressions of CD68 and CD206 were increased; The relative mRNA expressions of TNF-α and IL-6 were both down-regulated, while those of TGF-β, IL-10 and Arg-1 were all up-regulated. Meanwhile, the protein levels of IL-10, Arg-1, and CD206 were also up-regulated, and all the differences were statistically significant (all P＜0.05). In conclusion, Ac2-26 treatment has improved hemodynamics and alleviated mitochondrial damage, leading to the recovery of cardiac function in AHF rats. The mechanism may be related to macrophage polarization change from M1 to M2.

Radiation-induced bystander effect (RIBE) is one of the mechanisms of ionizing radiation-induced biological effects, which may be mediated by a variety of pathways. Exosomes are 30~150 nm diameter bilayer lipid membrane-rounding vesicles actively released by living cells and were widely distributed in body fluids. They carry signal molecules including nucleic acids and proteins to play important roles in inter-cellular communications. Recently, it has been found that exosomes can participate in the formation of RIBE and mediate the occurrence of immune responses due to ionizing radiation. The immune system is one of the main targets for ionizing radiation, and the damage of the immune system is also the main cause of the most common diseases and  life quality decline of patients suffering from nuclear accidents. Therefore, it has persisted a hotspot in the field of radiation biology to comprehensively reveal the mechanism of RIBE in the ionizing radiation-induced immune effect. This review discusses the role of RIBE in the ionizing radiation-induced immune effect  from the perspective of exosome and summarizes the biological mechanisms of exosome in this process in order to form a scientific basis for further study of the mechanism of radiation biological effects and for the exploration of radiation injury prevention and treatment strategies.

Aging is an inevitable stage in the metabolic process of human body which also affects the immune system, among which the changes of T cells are the most obvious. Mitochondrial dysfunction is one of the important reasons for cellular senescence. Recent studies have shown that viral infection can alter the metabolism of host cells by inducing mitochondrial damage which causes immunosenescence. This review aims to summarize the research progress on the role of virus infection-induced mitochondrial damage in T cell senescence including mitochondrial function, the effect of virus infection on mitochondrial damage, and the relationship between mitochondrial damage and T cell senescence.

Obesity increases the risk of infectious and neoplastic diseases. Studies have found that obesity may cause T cell metabolism disorders by affecting T cell lipid and carbohydrate metabolisms, promoting the release of inflammatory factors, and T cell aging, thereby increasing the mortality upon infection. Obesity is also an important risk factor associated with the prevalence of diseases. Obesity is associated with poor prognosis of neoplastic diseases, which is the combined effect of multiple factors affecting immune metabolism and inflammation. This review summarizes the research progress on T lymphocyte metabolism disorders caused by obesity and the role of T lymphocyte metabolism disorders in infectious and neoplastic diseases and treatment prospects.

To investigate the role and mechanism of long non-coding RNA (LncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in immune escape of non-small cell lung cancer (NSCLC), the tumor tissues and adjacent normal tissues of 96 NSCLC patients were collected in this study.  qRT-PCR was used to detect the expression of NEAT1 in NSCLC tumors and normal tissues, and its correlation with the clinicopathologic feature of NSCLC patients was analyzed.  In addition, qRT-PCR was used to detect the expression of NEAT1, miR-128-3p, heterogeneous nuclear ribonucleoprotein L (HNRNPL), and PD-L1 mRNAs in bronchial epithelial cells 16HBE and NSCLC cell lines. NEAT1 interference plasmid (si-NEAT1), miR-128-3p inhibitor, and controls (si-NC and inhibitor-NC) were transfected into A549 cells and divided into control group, si-NC group, si-NEAT1 group, si-NEAT1+anti-NC group, and si-NEAT1+anti-miR-128-3p group. The mRNA and protein expressions of HNRNPL and PD-L1 were measured and the regulatory mechanisms of NEAT1, miR-128-3p, and HNRNPL were verified by RNA pull-down experiment. A549 cells were co-cultured with CD8⁺ T cells to verify the role of NEAT1 knockdown in NSCLC immune escape. The levels of PD-L1 and IFN-γ were detected by ELISA. The results showed that NEAT1 was highly expressed in NSCLC tumor tissues, and it significantly correlated with NSCLC tumor size, TNM stage, and lymph node metastasis (P<0.05). In NSCLC tumor cells, NEAT1, HNRNPL, and PD-L1 were significantly overexpressed, while miR-128-3p was significantly underexpressed (all P<0.05). Knockdown of NEAT1 up-regulated miR-128-3p while inhibiting HNRNPL and PD-L1 expressions, which in turn significantly reduced NSCLC cell viability and induced NSCLC cell apoptosis (all P<0.05). NEAT1 targeted and bound miR-128-3p in NSCLC cells. In the co-culture system, knocking down NEAT1 in A549 cells could activate CD8⁺ T cells, inhibit their apoptosis and reduce the levels of PD-L1 and IFN-γ (all P<0.05). Down-regulation of miR-128-3p increased the expressions of HNRNPL and PD-L1, and attenuated the impact of NEAT1 knockdown on NSCLC cell proliferation, apoptosis, and CD8⁺ T cell activation (all P<0.05). Therefore, NEAT1 may promote PD-L1 expression through the miR-128-3p/HNRNPL axis, thereby leading to immune escape in NSCLC.

To explore the clinical characteristics of DNA topoisomerase type Ⅰ (AC-29)  in human laryngeal carcinoma cell line 2 (HEp-2) cells, four cases of AC-29 from Children's Hospital of Nanjing Medical University were retrospectively reported. From January 2020 to December 2021, a total of 14 213 serum samples with auto-antibodies had been tested in this Hospital. Among them, four had the anti-nuclear antibody (ANA) karyotype shaped AC-29 tested by indirect immunofluorescence assay. AC-29 is a newly defined karyotype in recent years. Correct identification of AC-29 has potential significance for early diagnosis of disease.

The aim of this research was to investigate the pharmaceutical effect of polydatin (PD) on the amelioration of acute myocardial infarction (AMI)-induced myocardial fibrosis in rat model. To this end, SD rats were randomly divided into control group (Ct), model group (Model), low-dose PD treatment group (PD-L, 40 mg/kg), high-dose PD treatment group (PD-H, 100 mg/kg), captopril treatment group (CTP, 20 mg/kg), and PD-H+TGF-β agonist group (100 mg/kg+30 mg/kg). AMI was induced by left anterior descending coronary artery ligation in all rats except those in the Ct group. Myocardial function and tissue structure were evaluated by animal ultrasound system and Masson staining of the heart. The collagen sedimentation in the myocardial tissue was evaluated by immunohistochemistry and the levels of IL-6 and TNF-α were measured by ELISA kits. The protein expressions of TGF-β1, p-Smad2/3, and p-ERK1/2 were assessed by Western blotting. Compared to those in the Ct group, rats in the model group exhibited worse myocardial function with severe myocardial fibrosis and systematic inflammatory responses (all P＜0.05). Notably, PD treatment significantly ameliorated AMI-induced myocardial injury in a dose-dependent manner, evidenced by improved myocardial function, less fibrotic collagen deposition, less inflammatory factors secretion along with the inhibition of the TGF-β/Smad/ERK signaling pathway (all P＜0.05). Moreover, the therapeutic effect of high-dose PD was comparable to that of positive control captopril whereas SRI-011381 (a type of TGF-β agonist) remarkedly abrogated the rescue effect of PD on the AMI-induced myocardial fibrosis. In conclusion, our study demonstrates that PD may relieve the degree of myocardial inflammatory infiltration and improve AMI-induced myocardial fibrosis in rats by inhibiting the TGF-β/Smad/ERK signaling pathway, which may promote damaged myocardium repairments.

Sex hormones are steroid hormones secreted by gonads and adrenal glands or converted from other substances. Sjogren's syndrome (SS) is a chronic progressive systemic autoimmune disease mediated by lymphocytes, mainly affecting exocrine glands. Due to the complex etiology, its pathogenesis has not been fully elucidated. The fact that the incidence of SS is higher in women than in men suggests a relationship between sex hormones and the development of SS. This review discusses the mechanism and influence of estrogen, androgen, and prolactin on SS to provide reference to understand the pathogenesis of SS and explore the therapeutic strategies.

In order to evaluate the therapeutic effect of dehydropachymic acid (DPA) on eczema rats and its effect on immune response, a rat model of eczema induced by dinitrochlorobenzene (DNCB) was established. Different concentrations of DPA (10, 40, and 80 mg/kg) were used to treat eczema rats for fourteen days, and compound glycyrrhizin (CG) (15 mg/kg) was used as the positive treatment control. H-E staining was used to observe the histopathological morphology of rat skin tissues. ELISA was used to detect the levels of serum IL-4 and IFN-γ as well as IgA, IgM and IgG. Concanavalin A (ConA)-activated lymphocytes were co-cultured with human keratinocyte HaCaT, followed by treatment of 40 μg/mL DPA. The proliferation of HaCaT cells was detected by MTT method, and the apoptosis of HaCaT cells was detected by TUNEL method. H-E staining outcomes showed that DPA relieved the skin lesions of eczema rats in a dose-dependent manner. DPA decreased the levels of serum IL-4, IgA, IgM and IgG in rats with eczema, and increased the level of IFN-γ (all with P＜0.05). The reliefs of eczema in middle-dose (40 mg/kg) and high-dose (80 mg/kg) DPA-treated rats were equivalent to that of 15 mg/kg CG-treated positive control rats. DPA did not affect the proliferation of HaCaT cells (P＞0.05). However, DPA inhibited the apoptosis of HaCaT cells co-cultured with lymphocytes (P＜0.05). Therefore, DPA regulates the immune function of the eczema rats by improving the Th1/Th2 balance, thereby alleviating eczema-related lesions.

Phagocyte nicotinamide adenine dinucleotide phosphate oxidase (NOX2), is a multicomponent enzyme complex that plays an important role in host immune defense and immune regulation. Functional defect of NOX2 correlates with the occurrence of chronic granulomatous disease (CGD). NOX2 deficiency may alter innate immune response which is the main cause of CGD infectious diseases. Further study on the pathogenesis of CGD finds that NOX2 deficiency may regulate T and B cell-mediated immune responses, thus affecting the occurrence and development of autoimmune diseases in CGD patients. This review discusses the changes in adaptive immunity caused by NOX2 deficiency and its relationship with concomitant autoimmune diseases in CGD patients.

Systemic lupus erythematosus (SLE), also known as typeⅠIFN signature disease, is a chronic systemic autoimmune disease of unknown etiology. The main features of the disease are the overactive immune response and overexpression of typeⅠIFN. In the course of innate immune response, the overactive immune reaction of nucleic acid receptor to pathogen and nucleic acid in vivo is one of the reasons that lead to the typeⅠIFN abnormality in patients. Regulating the overactive immune response and the overexpression of typeⅠIFN play important roles in alleviating the disease. Autophagy, as an important process regulating body homeostasis, can inhibit the typeⅠIFN response. In this review, we discuss how the selective autophagic receptors tripartite motif 21 (TRIM21), stimulator of interferon genes (STING), and p62 affect typeⅠIFN response by mediating autophagy of key regulators in multiple pathways. 

The tumor microenvironment (TME) is a complex cellular environment around tumor consisting of tumor cells, immune cells, and stromal cells, which plays a crucial role in tumorigenesis. Among tumor-infiltrated immune cells, a major composition and functional significant population is the myeloid cells (including tumor-associated macrophage [TAM], mast cell [MC], DC, tumor-associated neutrophil [TAN], and myeloid-derived suppressor cell [MDSC]). They have a complex dual regulatory role in both cancer promotion and suppression and affect tumor growth, invasion, metastasis, and death. This review focuses on the research progress of how multiple myeloid cells in the TME regulate the occurrence and development of hepatocellular carcinoma (HCC).

The aim of this study is to explore the protective effect and mechanism of rosmarinic acid (RA) on rats with sepsis and acute kidney injury. The kidney injury models of sepsis were constructed by cecal ligation and puncture (CLP) and the rats were randomly divided into sham operation group, model group, RA groups (12.5, 25, 50 mg/kg), and dexamethasone (Dex, 1 mg/kg) group. H-E staining of kidney tissues, renal function indexes, oxidative stress indexes, apoptosis of kidney tissues, and expressions of NF-κB and p38 MAPK signaling pathway proteins were compared among the groups. The results showed that compared to the model group, the RA groups (25, 50 mg/kg) and Dex group had significantly decreased levels of serum creatinine (Scr), blood urea nitrogen (BUN), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), TNF-α, IL-1β, IL-6, malondialdehyde (MDA), number of apoptosis cells in kidney tissues, cleaved Caspase-3/Caspase-3, cytochrome c (Cyt c), cleaved poly(ADP-ribose) polymerase (cleaved PARP), phosphorylated p65 (p-p65)/p65 and phosphorylated p38 (p-p38)/p38 (P<0.05). In contrast, the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased in RA groups (25, 50 mg/kg) and Dex group (P<0.05). In addition, the improvement of the above indexes was more significant in RA group (50 mg/kg) and Dex group (P<0.05). The study suggests that RA inhibits NF-κB and p38 MAPK signaling pathways, alleviates inflammation response and oxidative stress, and reduces apoptosis of kidney tissues to improve sepsis and acute kidney injury.

To understand the therapeutic effect and mechanism of shikonin (Shi) on myocardial injury in spontaneous hypertension rat (SHR), rats were divided into Wistar-Kyoto (WKY) group, SHR model group, SHR+Shi treatment group (Shi 50 mg/［kg·d］), and SHR+losartan(Los) treatment group (Los 10 mg/ ［kg·d］). The rats were treated for 4 consecutive weeks. The left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD) were analyzed by echocardiography. H-E staining kit, Sirius scarlet staining kit, and Masson tricolor staining kit were used for histopathological examinations. The myocardial injury (atrial natriuretic peptide ［ANP］ and lactate dehydrogenase ［LDH］), inflammation (IL-17 and TGF-β), and oxidative stress (superoxide dismutase ［SOD］, catalase ［CAT］ and malondialdehyde ［MDA］ ) parameters of rats in each group were measured. The expressions of Notch2 and Hes1 in myocardial tissue were detected by RT-PCR and Western blotting. The results showed that compared to those of the SHR group, the LVEF and LVFS of the SHR+Shi group and SHR+Los group were significantly increased（P<0.05）, while the LVEDD and LVESD were significantly decreased (P<0.05). The area of myocardial fibrosis in the SHR group was increased, while the areas of myocardial fibrosis in the SHR+Shi group and the SHR+Los group were significantly reduced. Compared to those of the SHR group, the plasma ANP and LDH levels of the SHR+Shi group and the SHR+Los group were significantly reduced (P<0.05), and the thickness of the thoracic aorta media was significantly reduced (P<0.05). In addition, the serum SOD and CAT levels were significantly increased（P<0.05）, while the MDA level was significantly decreased (P<0.05) in the SHR+Shi group and the SHR+Los group. Compared to those of the SHR group, the serum IL-17 levels of the SHR+Shi group and the SHR+Los group were significantly reduced（P<0.05）, while the TGF-β levels were significantly increased (P<0.05). The mRNA and protein expressions of Notch2 and Hes1 in the myocardium of the SHR+Shi group and the SHR+Los group were significantly reduced (P<0.05) compared to those of the SHR group. This study shows that Shi can alleviate myocardial injury in SHR  by inhibiting inflammation and oxidative stress via down-regulation of the Notch2 pathway.

 To explore the mechanism of γδT cell receptor in global cerebral ischemia-reperfusion injury after cardiopulmonary-cerebral resuscitation (CPCR) in mice, adult male C57BL/6 mice were randomly divided into three groups: blank group, CPCR group, and CPCR+γδT receptor antagonist group. The model of global cerebral ischemia-reperfusion injury in mice after CPCR was established by asphyxia and then paraffin sections of mouse brain tissue were made. H-E staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) were used to observe the injury and apoptosis of cerebral tissue. Western blotting and immunohistochemistry were used to evaluate the protein expression levels of  IL-17A and IL-23p19. The mRNA expression levels of IL-17A and IL-23p19 were evaluated by RT-PCR. The results showed that compared to those of the blank group, large numbers of cells in the central area of cerebral ischemia foci in the CPCR group were dead or showed irregular state of enlargement, rupture of nuclear membrane, and disappearance of cell structure. And the apoptosis in the CPCR group was more severe than that in blank group. In contrast, all the above manifestations were less severe in CPCR+γδT receptor antagonist group. Compared to those in the blank group, the brain injury score, apoptosis rate, IL-17A and IL-23p19 expressions were significantly increased in the CPCR group (P<0.01). Compared to the CPCR group, the CPCR+ γδT receptor antagonist group had significantly lower brain injury score, apoptosis rate, IL-17A and IL-23p19 expressions (P<0.05). These results suggest that the γδT cell receptor plays a proinflammatory role in the pathogenesis of global cerebral ischemia-reperfusion injury after CPCR in mice by regulating the levels of IL-17A and IL-23p19 in γδT cells.

This study aimed to investigate the effects of sodium butyrate (NaB) on plaque formation and inflammatory responses in atherosclerotic (AS) rats through the nucleotide-binding oligodomain-like receptor 1 (NOD1)/receptor-interacting protein 2 (RIP2)/NF-κB signaling pathway. AS model on 41 rats was given by combination of balloon injury and high-fat diet (HFD), and a total of thirty-six rats were successfully modeled. Thirty-six AS rats were divided into model group, NaB group, and NaB+NOD1 agonist γ-D-glu-mesodiaminopimelic acid (iE-DAP) group, with 12 rats in each group. The sham operation group rats were only given exposure of left common carotid artery and successive suture. The model group, NaB group and NaB+iE-DAP group were cultured with HFD while the sham operation group was cultured routinely.  NaB group was gavaged with 10 g/(kg·d) NaB, NaB+iE-DAP group was gavaged with 10 g/(kg·d) NaB and peritoneally injected with 1 mL/(each·week) iE-DAP; Model group and sham operation group were gavaged and peritoneally injected with the same volume saline; All the above treatments lasted for twelve weeks. Aorta histomorphology was evaluated by H-E staining. The levels of serum TG, TC, LDL-C, HDL-C, ox-LDL, MCP-1, hs-CRP, TNF-α, and IL-1 were measured by ELISA. Immunohistochemistry was performed to measure ICAM-1 protein expression in the aorta and western blotting was used to measure the protein levels of NOD1, RIP2 and NF-κB in the aorta. The results showed that the aorta lesion was severe in the model group, alleviated in the NaB group and aggravated in the NaB+iE-DAP group. Compared to those of the sham operation group, the serum levels of TG, TC, LDL-C, ox-LDL, MCP-1, hs-CRP, TNF-α，and IL-1, the positive rate of aortic ICAM-1, the expression levels of NOD1, RIP2 and nuclear NF-κB in the model group were significantly increased (all with P＜0.05), while the levels of HDL-C and cytoplasmic NF-κB protein were significantly decreased (both P＜0.05). In the NaB group, all these indexes showed changes in the reverse direction. Compared to those of the NaB group, the above indicators in the NaB+iE-DAP group all increased significantly while HDL-C and cytoplasmic expression of NF-κB decreased (all with P＜0.05). This study suggests that NaB inhibit NOD1/RIP2/NF-κB signaling pathway to relieve plaque formation and inflammatory responses in AS rats.

To study the influence of miR-409-3p on myocardial injury in young mice with Kawasaki disease (KD) through silent information regulator 1 (SIRT1)/forkhead transcription factor O1 (FOXO1) signaling pathway, SD juvenile male rats were randomly divided into control group, model group, miR-409-3p antagomir group, miR-409-3p antagomir negative control group, EX527 (SIRT1 inhibitor,  1 μg/kg) group, and miR-409-3p antagomir+EX527 (1 μg/kg) group, 12 per group. The expression of miR-409-3p in rat myocardium was detected by qRT-PCR; ELISA was performed to detect levels of creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), cardiac troponin T (cTnT), TNF-α, IL-17, IL-18 in serum. The result showed that compared with the model group and the miR-409-3p antagomir+EX527 group, the pathological injuries in myocardial tissue of the miR-409-3p antagomir group were alleviated, the serum CK-MB, cTnI, cTnT, TNF-α, IL-17, and IL-18 levels, myocardial acely-FOXO1/FOXO1 were decreased (P<0.05), the cardiac function indexes the left ventricular ejection fraction (LVEF) and the left ventricular fractional shortening (LVFS), and the expression of SIRT1 in myocardial tissue were increased (P<0.05); the pathological injuries in myocardial tissue of   the EX527 group were aggravated, the serum CK-MB, cTnI, cTnT, TNF-α, IL-17, and IL-18 levels, myocardial acely-FOXO1/FOXO1 were increased (P<0.05), the cardiac function indexes LVEF and LVFS, and the expression of SIRT1 in myocardial tissue were decreased (P<0.05). miR-409-3p was able to target down-regulation of SIRT1 expression in rat cardiomyocytes. The study suggests that miR-409-3p can target down-regulate SIRT1 expression to participate in the process of myocardial injury in KD young rats. Down-regulation of miR-409-3p expression can play an anti-inflammatory effect by activating SIRT1/FOXO1 signal, thereby reducing myocardial injury in KD young rats.