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.

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. 

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.

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.

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.

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.

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.

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. 

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.

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.

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.

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.

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.

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.

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.

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. 

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 mechanism by which salidroside improves keloid on regulating JAG1/Notch3 signaling pathway through miR-26a-5p, 10 keloid patients diagnosed by histopathology in Wuhan Hospital of Traditional Chinese Medicine were enrolled as the research objects from October 2019 to January 2021. The keloid tissues removed by surgery were used in the keloid group, and the adjacent healthy skin tissues were used in the normal group. Primary keloid fibroblasts were isolated and cultured, and the cells of generation 4~8 were divided into 8 groups: control group (normal culture), salidroside low-dose group (10 μmol/L salidroside), salidroside medium-dose group (20 μmol/L salidroside), salidroside high-dose group (40 μmol/L salidroside), miR-NC group (40 μmol/L salidroside+miR-NC), miR-26a-5p inhibitor group (40 μmol/L salidroside+miR-26a-5p inhibitor), sh-RNA group (40 μmol/L salidroside+miR-26a-5p inhibitor+sh-RNA) and sh-JAG1 group (40 μmol/L salidroside+miR-26a-5p inhibitor+sh-JAG1). Cells in each group were treated with salidroside for 24 h after transfection or directly treated with the corresponding dosage of salidroside for 24 h. The relative mRNA expressions of miR-26a-5p and JAG1  in tissues and cells were quantified using qRT-PCR. Cell proliferating viability was measured by the MTT assay and cell cloning capacity was detected using the plate cloning method. Cell apoptosis was detected by FACS and cell migration and invasion were assessed by Transwell method. Luciferase reporter system was utilized to examine the targeting interaction between miR-26a-5p and JAG1. Western blotting was used to detect the expressions of tissue hyperplasia-related proteins. The results showed that, compared to that of the normal group, the expression of miR-26a-5p in keloid group was significantly decreased (P＜0.05), while the JAG1  expression significantly increased (P＜0.05). Compared to the 0 μmol/L salidroside group, 10, 20, 40, 80, and 160 μmol/L salidroside treatment inhibited the survival rate of keloid fibroblasts in a concentration-dependent manner (all with P＜0.05). To ensure both the survival of keloid fibroblasts and the effect of salidroside, subsequent experiments were conducted with salidroside concentrations of 10, 20, and 40 μmol/L (It was proved that miR-26a-5p combines to JAG1). In the three salidroside groups, compared to those of the control group, the expression of miR-26a-5p and the apoptosis rate increased dependently, while the expression of JAG1, the numbers of cell clones, cell migrations, and invasions, and the expression of α-SMA, collagen Ⅰ, collagen Ⅲ, JAG1, and Notch3 proteins decreased significantly (all with P＜0.05). Compared to those of the salidroside high-dose group and the miR-NC group, the expression of miR-26a-5p and the cell apoptosis rate in the miR-26a-5p inhibitor group reduced significantly, while the expression of JAG1, the numbers of cell clones, migration and invasion, and the expression of α-SMA, collagen Ⅰ, collagen Ⅲ, JAG1 and Notch3 proteins increased significantly (all with P＜0.05). Inhibition of JAG1  expression suppressed the effect of miR-26a-5p inhibitor on promoting cell proliferation, migration and invasion, and on inhibiting cell apoptosis. In conclusion, the expression of miR-26a-5p is down-regulated and JAG1  is up-regulated in keloid tissue, salidroside can inhibit the JAG1/Notch3 signaling pathway and the proliferation, migration and invasion of keloid fibroblasts, while promoting cell apoptosis, which in turn improves keloid by up-regulating the expression of miR-26a-5p.

Age-associated B cell (ABC) is a new B cell subset discovered in recent years, which accumulates in spleen with age. This type of cell has unique cellular phenotypes and transcriptional features. ABC highly expresses myeloid marker CD11c and transcription factor T-bet, and differentiates and proliferates upon the stimulation of Th1 cytokines and TLR7 and/or TLR9. It can differentiate into plasma cells to produce antibodies, secrete cytokines, and present antigens. ABC plays an important role in immune aging and autoimmune disease. This review aims to introduce the phenotypic characteristics, origin, anatomical distribution, differentiation regulation mechanism, and function of ABC, clarify its role in immune aging and autoimmune diseases, and provide a new target for clinical treatment.

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 effect of matrix metalloproteinase 7 (MMP-7) over-expression on macrophage polarization, galectin 3 (Gal-3) and inflammatory factors secretions, THP-1 cells were induced to macrophages and transfected with MMP-7 over-expressing plasmid or empty vector. The cells were divided into control group, MMP-7 over-expressing group, MMP-7 NC group, M1-polarized group, and M2-polarized group. mRNA expression levels of Gal-3 and MMP-7 were quantified by qPCR. The percentages of F4/80⁺, CD86⁺, and CD206⁺ macrophages were detected by flow cytometry. The expressions of inflammatory cytokines IL-1α, IL-6, and TGF-β were detected by ELISA. After Gal-3 inhibitor treatment on M1-induced and M2-induced macrophages, the mRNA expression of Gal-3 in above macrophages was detected by qPCR, and the levels of IL-1α, IL-6, and TGF-β in the supernatant of cell cultures were detected by ELISA. The results showed that compared to the control group, the MMP-7 over-expressing group and the M2-polarized group showed significant increase in the expressions of Gal-3 and MMP-7 mRNA, in the percentage of (F4/80⁺)/CD206⁺ macrophages (all with P＜0.01), and in the concentrations of TGF-β（both P＜0.01), while IL-1α and IL-6 levels showed significant decrease (both P＜0.01). In the M1-polarized group, the percentage of (F4/80⁺)/CD86⁺ macrophages increased significantly (P＜0.01). The concentration of TGF-β decreased, while the concentrations of IL-1α and IL-6 increased significantly (all with P＜0.01). Compared to that of the M1-polarized group, the relative expression of Gal-3 mRNA in the M1+Gal-3 inhibitor group was significantly decreased (P＜0.01), the concentration of TGF-β significantly increased (P＜0.01), while the IL-1α and IL-6 levels significantly decreased (both P＜0.01). Compared to those of the M2-polarized group, the relative expression of Gal-3 mRNA in M2+Gal-3 inhibitor group was significantly decreased (P＜0.05), along with decreased IL-1α and IL-6 and increased TGF-β concentrations (all with P＜0.05). This study demonstrates that MMP-7 can activate Gal-3 expression to promote M2-type macrophage polarization and present anti-inflammatory activity.

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.

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.

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).

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.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of bone marrow-derived cells that are abundantly accumulated in patients and mouse models of diabetic nephropathy (DN). Studies have shown that MDSC-derived exosomes (EXs) have obvious immuno-suppressive functions, which may inhibit the development of inflammation in DN. This study aims to investigate the immuno-suppressive capacity of EX derived from MDSC (MDSC-EX) and its effect on DN mice. DN mice were established through high-fat diet and intra-peritoneal injection of streptozotocin (STZ). Two subsets of MDSC, polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (MO-MDSC), were isolated from DN mice spleens by magnetic-activated cell-sorting (MACS). PMN-MDSC and MO-MDSC-derived EXs were prepared from the culture supernatants of PMN-MDSCs and MO-MDSCs and FACS was used to examine their inhibitory effect on CD3⁺T cell proliferation. PMN-MDSC-EX or MO-MDSC-EX were caudal vein injected into DN mice and the effects on fasting blood glucose (FBG）, body weight (BW), total protein in urine within 24 hours (TPU), urea nitrogen in serum (UNS), creatinine in serum (CS) and glomerular filtration rate (GFR) were observed. H-E staining of kidney was observed under microscope and the protein expressions of fibronectin, collagen type Ⅳ (collagen Ⅳ), and alpha smooth muscle actin (α-SMA) in kidney tissues were measured by western blotting. The results showed the successful establishment of  DN mouse model and the isolation of PMN-MDSC-EX and MO-MDSC-EX. Compared to MO-MDSC-EX, PMN-MDSC-EX had a greater capacity to inhibit the proliferation of CD3⁺T lymphocytes (P＜0.05). Compared to MO-MDSC-EX, PMN-MDSC-EX decreased the FBG, TPU, UNS, and CS in DN mice to a larger extent, and increased the BW and GFR significantly (all with P＜0.05). Intervention with both PMN-MDSC-EX and MO-MDSC-EX significantly alleviated kidney tissue damage in DN mice. Compared to MO-MDSC-EX, PMN-MDSC-EX presented a better inhibitory effect on glomerulosclerosis in model mice. In conclusion, PMN-MDSC-EX has a stronger protective effect on DN mice than MO-MDSC-EX, which highlights a novel path to DN treatment.

Aiming to explore the underlying mechanism of Zhilong Tongluo capsule on protecting rats with adriamycin(ADR)-induced nephropathy from renal fibrosis, renal fibrosis rat model was established by right side nephrectomy and multiple caudal vein injections of 3 mg/kg ADR. After successful model establishment, rats were divided into model group, Zhilong Tongluo capsule group and Zhilong Tongluo capsule+activator group, and rats without treatment were used as control. Rats in Zhilong Tongluo capsule group were gavaged with Zhilong Tongluo capsule suspension, rats in Zhilong Tongluo capsule+activator group were additionally intraperitoneally injected with LPS (5 mg/kg), and rats in blank control group and model group were treated with same volume of saline. All treatments lasted for 8 weeks. The general conditions of rats and body weight (BW) changes were recorded. The 24 h urine protein (24 h UPO), creatinine (Cr), and blood urea nitrogen (BUN) were detected by urine protein quantification kit and ELISA kit. The rats were sacrificed and then renal tissues were collected for pathological study. The fibrosis of renal tissues was observed after Masson staining. The mRNA and protein levels of TLR4, NF-κB, and TGF-β1 were measured by qRT-PCR and immunohistochemistry. Compared to that of the blank control group, BW was decreased, while the collagen proportionate area (CPA), 24 h UPO, Cr, and BUN were increased in the model group. The mRNA and protein levels of TLR4, NF-κB, and TGF-β1  were also significantly increased (all with P＜0.05). Compared to those of the model group, the BW of rats was increased, and CPA, 24 h UPO, Cr, and BUN were decreased in the Zhilong Tongluo capsule group. The mRNA and protein levels of TLR4, NF-κB, and TGF-β1  were significantly decreased (all with P＜0.05). Compared to those of the Zhilong Tongluo capsule group, the BW was decreased, CPA, 24 h UPO, Cr, and BUN were increased in the Zhilong Tongluo capsule+activator group while the mRNA and protein levels of TLR4, NF-κB, and TGF-β1  were all significantly increased (all with P＜0.05). In conclusion, Zhilong Tongluo capsule may mitigate fibrosis of renal tissues and alleviate renal damage by inhibiting the expression of the TLR4/NF-κB/TGF-β1 signaling pathway.

To investigate the effects and mechanism of D-limonene, the active ingredient of Xiefeiqingganyin, on inflammatory and immune responses in mice with chronic obstructive pulmonary disease (COPD), 36 6-week-old male C57BL/6J mice were randomly divided into three groups: control group, model group, and D-limonene group, with 12 mice in each group. The COPD model were established by administration of LPS and smoking. Mice in D-limonene group were intraperitoneally injected with 100 mg/kg D-limonene daily from the 2nd day of modeling until the 28th day. The hair, movement, and mental state of mice in each group were observed, and the body mass was recorded. Pathological changes of mouse lung tissues were observed by H-E staining. Western blotting was used to detect the expression of NF-κB and p-NF-κB protein in lung tissues, and ELISA was used to detect the levels of IL-6, TNF-α, IL-1β, and IL-10 in serum and bronchoalveolar lavage fluid (BALF). FACS was used to detect the ratio of Th17/Treg in peripheral blood. The results showed that compared to control group, mice in model group showed more severe symptoms including weight loss, listless and decadent, dull coat and hair loss, reduced activity, abnormal alveolar structure, hyperplasia of bronchial epithelium, and increased infiltration of inflammatory cells around the lung tissues. In addition, the expression of p-NF-κB protein in lung tissue, the levels of IL-6, TNF-α, and IL-1β in serum and BALF, and the ratio of Th17/Treg in peripheral blood were all significantly increased (P<0.01), while IL-10 in serum and BALF was significantly decreased (P<0.01). These changes were significantly reversed after D-limonene administration (P<0.01). Altogether, this study suggests that D-limonene has a good therapeutic effect on COPD mice by restoring the Th17/Treg balance and reducing the expressions of inflammatory factors by inhibiting NF-κB pathway. 

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 investigate the effect of leonurine (LEO) on Henoch-Schonlein purpura nephritis (HSPN), mice were divided into the blank control group, the model group, the low (25 mg/[kg·d]), medium (50 mg/[kg·d]) and high (100 mg/[kg·d]) doses of LEO treatment groups. The 24-hour urinary albumin (Alb) content was measured by the Bradford method and urine red blood cells were counted. The serum creatinine (Cr) and blood urea nitrogen (BUN) were measured by the automatic biochemical analyzer. Immunofluorescence staining was used to detect IgA deposition in renal tissues. The histopathological changes in renal tissues were observed by H-E staining. ELISA was performed to detect serum IL-4, IL-10, IFN-γ, and TNF-α. Serum circulating immune complex levels were measured by polyethylene glycol precipitation turbidimetry, and the peripheral blood Th1/Th2 ratio was measured by flow cytometry. The results showed that compared to those of the blank control group, the 24-hour urinary Alb level, urine red blood cell count, and serum levels of Cr, BUN, IL-4, IL-10, and circulating immune complex of the model group were significantly higher, whereas the serum IFN-γ, TNF-α levels, and peripheral blood Th1/Th2 ratio were significantly lower (P<0.05). Compared to those of the model group, the 24-hour urinary Alb level, urine red blood cell count, serum Cr, BUN, IL-4, IL-10, and circulating immune complex levels were significantly reduced, while the serum IFN-γ, TNF-α levels, and peripheral blood Th1/Th2 ratio were significantly increased in all the LEO treatment mice (P<0.05). In addition, the effect of LEO was dose-dependent (P<0.05). Taken together, this study suggests that LEO treatment reduces renal tissue damage and improves renal function and renal protection in HSPN mice. The underlying mechanism may be related to the promotion of Th1/Th2 balance which helps to restore normal immune function.

Inflammatory diseases are a series of acute or chronic diseases caused by inflammatory response to stimulation, which may seriously harm human health. Traditional Chinese medicine, which has multiple targets in immunomodulatory processes, plays a key role in the treatment of various inflammatory diseases. Corilagin is one of the major bioactive compounds in many medicinal plants. It has a variety of biological and pharmacological activities, including anti-oxidation, anti-inflammatory, liver protection, anti-virus, anti-hypertension, anti-infection, and anti-tumor. It has attracted extensive attention in recent years. However, there is a lack of systematic understanding of the role corilagin plays in inflammatory diseases. To better develop and utilize the medicinal plant resources in China, this review summarizes the role and related mechanism of corilagin in various inflammatory diseases. It will provide references for both follow-up basic research and clinical application of corilagin.

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.

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.

This study aims to investigate the protein and mRNA expressions of IL-22 and aryl hydrocarbon receptor （AhR）in the peripheral blood of patients with systemic lupus erythematosus (SLE), and to analyze the correlation between IL-22 and AhR and SLE disease activity index (SLEDAI). The expression levels of IL-22 and AhR protein in the peripheral blood of 43 SLE patients (25 in active stage and 18 in inactive stage) and 41 healthy controls were measured by ELISA. The expression levels of IL-22 and AhR mRNA in PBMC of SLE patients, healthy controls, and 31 rheumatoid arthritis (RA) patients by qRT-PCR. Spearman analysis was used to calculate the correlations of IL-22 and AhR protein and mRNA levels with the SLEDAI in SLE patients. ROC curve was used to analyze the combined diagnostic effect of anti-dsDNA antibody, IL-22, and AhR protein levels in SLE. The results showed that the levels of IL-22, AhR protein and mRNA were higher in SLE patients than those in healthy controls (P<0.001), and they were all higher in the active phase than in the inactive phase (P<0.05). IL-22 expressions were significantly elevated in SLE patients compared to RA patients (P<0.05). Spearman analysis showed that IL-22, AhR protein and mRNA levels were all positively correlated with SLEDAI in SLE patients (P<0.01). The AUC of combined diagnosis of IL-22, AhR, and anti-dsDNA antibody for SLE was 0.986, with a sensitivity and specificity of 90.7% and 97.6%, respectively. In conclusion, the protein and mRNA levels of IL-22, AhR in SLE patients are significantly higher than those in healthy subjects and are positively correlated with SLEDAI. The diagnosis of serum IL-22 and AhR combined with anti-dsDNA antibody has higher accuracy and may improve the clinical diagnosis of SLE in the future.

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.

Genetically engineered modification of antibodies generates various types of new small molecule antibodies, among which single-chain antibody (ScFv) has indisputable advantages including high specificity, high affinity, tissue permeability, excellent stability and low immunogenicity, easy preparation, and large-scale production, etc. ScFv has been widely applied in the fields of drug development and disease treatment. This review summarizes the new research progress and medical application of ScFv.

The aim of this study was to investigate the effect of suppressor of cytokine signaling 3 (SOCS3) on the  high glucose(HG)-induced inflammatory factors expression in rat glomerular mesangial cell (RMC) and the related mechanism. For this purpose, RMCs were divided into six groups: normal control (NC) group, osmotic control (OSM) group, HG group, HG+TAK-242 (TLR4 inhibitor) group, HG+sh-SOCS3 group, and HG+sh-SOCS3+TAK-242 group. Cell viability was detected by CCK-8 assay and cell apoptosis was detected by FACS. The levels of inflammatory factors TNF-α, IL-1β, IL-6, and COX2 in cell culture supernatant were detected by ELISA. The mRNA expressions of TLR4, NF-κB p65, and IκB-α in RMC were detected by qPCR. The protein expressions of TLR4, NF-κB p65, p-p65, IκB-α, and p-IκB-α were detected by western blotting. The results showed that compared to those of  NC group, the cell survival rate of the HG group was significantly decreased (P＜0.01), while the cell apoptosis rate, the levels of TNF-α, IL-1β, IL-6 and COX2 in cell culture supernatant, the mRNA expression of TLR4, p65 and IκB-α and the protein expression of TLR4、p-p65 and p-IκB-α were significantly increased (all with P＜0.01). Compared to those of  HG group, the cell survival rates of the HG+TAK-242 group and the HG+sh-SOCS3 group were significantly increased (both P＜0.05) while the apoptosis rate, the levels of TNF-α, IL-1β, IL-6 and COX2 in the cell culture supernatant, the mRNA expression of TLR4, p65, and IκB-α, and the protein expression of TLR4, p-p65, and p-IκB-α were significantly decreased (all with P＜0.05). The above changes were more significant in the HG+sh-SOCS3+TAK-242 group than the HG+TAK-242 group (all with P＜0.05). Taken together, SOCS3 up-regulates the expression of inflammatory factors in RMCs cultured with HG by activating the TLR4/NF-κB signaling pathway, thus aggravates the inflammatory responses.

The aim of this paper was to investigate the expression of myocyte enhancer factor 2A (MEF2A) gene in myeloproliferative neoplasm (MPN) and its relation with tumor cell proliferation and angiogenesis. From January 2020 to December 2021, PBMC specimens were collected from 30 healthy volunteers and 60 MPN patients in the Affiliated Hospital of Guilin Medical University. Additionally, MPN tumor cell lines HEL92.1.7 (abbreviated HEL), UKE-1, and SET-2 were cultured and used for cellular study. qRT-PCR and western blotting were used to detect the expression levels of MEF2A mRNA and protein. HEL and UKE-1 cells were transfected with MEF2A knock-down or over-expressing plasmid, respectively. Cell viability and monoclonal formation capacity were evaluated by CCK-8 assay and crystal violet staining. Cell apoptosis rate was measured by FACS with Annexin Ⅴ-FITC/PI double staining. The in vitro angiogenic ability was determined by catheter formation assay. The expressions of proteins related to apoptosis, angiogenesis and p38 MAPK signaling pathway were quantified by western blotting. The results showed that the mRNA and protein expressions of MEF2A in PBMCs of MPN patients were significantly higher than those of healthy volunteers (both P＜0.05). The expression levels of MEF2A mRNA and protein in MPN cell lines were also significantly higher than those of PBMCs from healthy  controls (all with P＜0.05). In HEL and UKE-1 cell lines, MEF2A over-expression caused increased cell proliferation, clone formation, angiogenesis, and the protein expressions of ANGPT2, FGF1, PDGFA, VEGF, Bcl-2, p-P38, and p-ERK (all with P＜0.05). In contrast, it decreased the cell apoptosis rate and the protein expressions of BAX and cleaved caspase 3 (cl-caspase-3)(all with P＜0.05). On the other hand, MEF2A knock-down resulted in the complete opposite effects (all with P＜0.05). In conclusion, MEF2A is broadly distributed in MPN cells at a relatively high level, and knock-down of MEF2A can inhibit the proliferation and angiogenesis while promoting the apoptosis of MPN tumor cells. MEF2A may function by regulating the MAPK signaling pathway.

The study aims to explore the effects of miR-153-3p on the proliferation, migration and invasion of esophageal cancer (ESCA) cells by targeting and regulating α-actinin 4 (ACTN4). The expression of miR-153-3p and ACTN4 mRNA in different cell lines was detected by qRT-PCR. The targeting relationship between miR-153-3p and ACTN4 was verified by double luciferase assay. ECA109 cells were cultured in vitro and divided into six groups: blank group, mimic control (miR-NC) group, mimic (miR-153-3p) group, empty vector group, ACTN4 overexpression (ACTN4) group, the mimic and ACTN4 overexpression (miR-153-3p+ACTN4) group. qRT-PCR and Western blotting were performed to measure the expression of miR-153-3p and ACTN4; CCK-8 and colony formation experiment was performed to measure the proliferation of cells; Transwell was performed to measure the migration and invasion of cells. Western blotting was used to detect the protein levels of Ki67, E-cadherin, and N-cadherin. A nude mouse model of subcutaneous xenograft tumors was constructed in vivo and the effect of up-regulation of miR-153-3p on tumor growth was detected. Immunohistochemistry was performed to measure the expression levels of ACTN4, Ki67, E-cadherin and N-cadherin in tumor tissues. The results showed that, the expression of miR-153-3p in the ESCA cell line was low (P<0.05), and ACTN4 mRNA was highly expressed (P<0.05). miR-153-3p was able to negatively regulate ACTN4 expression (P<0.05). Overexpression of miR-153-3p can reduce cell viability, colony formation, migration and invasion, inhibit Ki67 and N-cadherin expression, and up regulate E-cadherin expression (P<0.05). ACTN4 overexpression showed the opposite effects (P<0.05); overexpression of ACTN4 can reverse the effects of miR-153-3p overexpression on ESCA cell behavior (P<0.05). In vivo studies have shown that overexpression of miR-153-3p can inhibit the expression of ACTN4, Ki67, N-cadherin, increase the expression of E-cadherin, and slow down tumor growth. This study suggests that overexpression of miR-153-3p may inhibit the proliferation, invasion and migration of ESCA cells by targeting ACTN4 negatively.

This study aims to investigate the changes in mRNA expressions of stimulator of interferon gene (STING) and cyclic GMP AMP synthase (cGAS), the composition of myeloid dendritic cells (mDC) and their surface maturation markers CD80 and CD86, the related cytokines, and the correlation among above indicators to analyze the immune response upon adenovirus pneumonia infection. 34 children with acute stage adenovirus pneumonia and 34 healthy children were included in the study. The relative mRNA expression levels of STING and cGAS in the peripheral mononuclear cells were detected by qRT-PCR. The levels of IFN-α, IFN-β, TNF-α, and IL-6 were detected by ELISA. FACS was used to detect the mDC composition and surface markers CD80 and CD86. The correlation of the above indicators was analyzed. The results showed that compared to those of the control group, mRNA expression levels of STING and cGAS, IFN-α, IFN-β, TNF-α, IL-6, mDC cell number, CD80, and CD86 were all increased in adenovirus pneumonia patients (P<0.05). The level of mDC was positively correlated with the expressions of STING mRNA, cGAS mRNA, IFN-α, TNF-α, and IL-6. The CD80 level was positively correlated with STING mRNA, cGAS mRNA, IFN-α, IFN-β, TNF-α, and IL-6, whereas CD86 was positively correlated with IFN-α, IFN-β, and TNF-α (P＜0.05). This study suggests that STING/cGAS genes are highly expressed in children with adenovirus pneumonia who exhibit increased mDC number, maturation markers, and cytokine secretion. The cGAS-STING pathway may be further activated to mediate innate immunity and exert antiviral effect.