The microenvironment of wound healing is susceptible to bacterial infection, chronic inflammation, oxidative stress, and inadequate angiogenesis, requiring the development of innovative wound dressings with antibacterial, anti-inflammatory, antioxidant, and angiogenic capabilities. This research crafted a new multifunctional bacterial cellulose composite membrane infused with copper-doped carbon dots (BC/Cu(II)-RCDs). Findings validated the successful loading of copper-doped carbon dots onto the BC membrane via hydrogen bonding interactions. Compared to the pure BC membrane, the BC/Cu(II)-RCDs composite membrane exhibited significantly enhanced hydrophilicity, tensile properties, and thermal stability. Diverse in vitro assays demonstrated excellent biocompatibility and antibacterial activity of BC/Cu(II)-RCDs composite membranes, alongside their ability to expedite the inflammatory phase and stimulate angiogenesis. In vivo trials corroborated the membrane\'s ability to foster epithelial regeneration, collagen deposition, and tissue regrowth in full-thickness skin wounds in rats while also curbing inflammation in infected full-thickness skin wounds. More importantly, the treatment of the BC/Cu(II)-RCDs composite membrane may result in the activation of VEGF and MAPK signaling proteins, which are key players in cell migration, angiogenesis, and skin tissue development. In essence, the developed BC/Cu(II)-RCDs composite membrane shows promise for treating infected wounds and serves as a viable alternative material for medicinal bandages.

OBJECTIVE: To identify the biomarkers for early rheumatoid arthritis (RA) diagnosis and explore the possible immune regulatory mechanisms.
METHODS: The differentially expressed genesin RA were screened and functionally annotated using the limma, RRA, batch correction, and clusterProfiler. The protein-protein interaction network was retrieved from the STRING database, and Cytoscape 3.8.0 and GeneMANIA were used to select the key genes and predicting their interaction mechanisms. ROC curves was used to validate the accuracy of diagnostic models based on the key genes. The disease-specific immune cells were selected via machine learning, and their correlation with the key genes were analyzed using Corrplot package. Biological functions of the key genes were explored using GSEA method. The expression of STAT1 was investigated in the synovial tissue of rats with collagen-induced arthritis (CIA).
RESULTS: We identified 9 core key genes in RA (CD3G, CD8A, SYK, LCK, IL2RG, STAT1, CCR5, ITGB2, and ITGAL), which regulate synovial inflammation primarily through cytokines-related pathways. ROC curve analysis showed a high predictive accuracy of the 9 core genes, among which STAT1 had the highest AUC (0.909). Correlation analysis revealed strong correlations of CD3G, ITGAL, LCK, CD8A, and STAT1 with disease-specific immune cells, and STAT1 showed the strongest correlation with M1-type macrophages (R=0.68, P=2.9e-08). The synovial tissues of the ankle joints of CIA rats showed high expressions of STAT1 and p-STAT1 with significant differential expression of STAT1 between the nucleus and the cytoplasm of the synovial fibroblasts. The protein expressions of p-STAT1 and STAT1 in the cell nuclei were significantly reduced after treatment.
CONCLUSIONS: CD3G, CD8A, SYK, LCK, IL2RG, STAT1, CCR5, ITGB2, and ITGAL may serve as biomarkers for early diagnosis of RA. Gene-immune cell pathways such as CD3G/CD8A/LCK-γδ T cells, ITGAL-Tfh cells, and STAT1-M1-type macrophages may be closely related with the development of RA.

Few symptoms persist for a long time after patients recover from COVID-19, called \"long COVID\". We explored the potential microbial risk factors for COVID-19 for a deeper understanding and assistance in the follow-up treatment of these sequelae.
Microbiome re-annotation was performed using whole blood RNA-Seq data collected from recovered COVID-19 patients and healthy controls at multiple time points. Subsequently, a series of downstream analyses were conducted to reveal the microbial characteristics of patients who recovered from SARS-CoV-2 infection.
The blood microbiome at 12 weeks post-infection was most evidently disturbed, including an increasing ratio of Bacillota/Bacteroidota and a higher microbial alpha diversity. In addition, a group of pathogenic microbes at 12 weeks post-infection were identified, including Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, which were positively associated with host genes involved in immune regulatory and olfactory transduction pathways. Several microbes, such as Streptococcus pneumoniae were associated with infiltrating immune cells, such as M2 macrophages.
This study provides insights into the relationship between the blood microbiome and COVID-19 sequelae. Several pathogenic microbes were enriched in recovered COVID-19 patients and thus affected host genes participating in the immune and olfactory transduction pathways, which play critical roles in COVID-19 sequelae.

The relationship between the tumor microenvironment and the network of key signaling pathways in cancer plays a key role in the occurrence and development of tumors. Tumor-associated macrophages (TAMs) are important inflammatory cells in the tumor microenvironment and play an important role in tumorigenesis and progression. Macrophages in malignant tumors, mainly the M2 subtype, promote tumor progression by producing cytokines and down-regulating anti-inflammatory immune responses. Several articles have investigated the effect of macrophages on the sensitivity of cancer chemotherapeutic agents, but few such articles have been reported in cholangiocarcinoma, so we investigated the effect of M2 macrophage on the sensitivity of cholangiocarcinoma cells to Lenvatinib compared to M1.
THP-1 monocytes were polarized to M0 macrophage by phorbol 12-myristate 13-acetate (PMA) and then induced to differentiate into M1 and M2 macrophages by LPS, IFN-γ and IL-4 and IL-13, respectively. Macrophages and cholangiocarcinoma cells were co-cultured prior to 24 hours of Lenvatinib administration, cancer cell apoptosis was detected by western-blot, FACS analysis of Annexin V and PI staining. Furthermore, we use xCELLigence RTCA SP Instrument (ACEA Bio-sciences) to monitor cell viability of Lenvatinib administration in co-culture of cholangiocarcinoma cells and macrophages. After tumorigenesis in immunodeficient mice, Lenvatinib was administered, and the effects of M2 on biological characteristics of cholangiocarcinoma cells were investigated by immuno-histochemistry.
mRNA and protein expression of M1 and M2 markers confirmed the polarization of THP-1 derived macrophages, which provided a successful and efficient model of monocyte polarization to TAMs. Lenvatinib-induced apoptosis of cholangiocarcinoma cells was significantly reduced when co-cultured with M2 macrophage, whereas apoptosis of cholangiocarcinoma cells co-cultured with M1 macrophage was increased. In the CDX model, Lenvatinib-induced cancer cell apoptosis was markedly reduced, and proliferative cells increased in the presence of M2 macrophages. Angiogenesis related factors was significantly increased in cholangiocarcinoma cells co-cultured with M2.
Compared with M1, M2 macrophages can inhibit the anti-tumor effect of Lenvatinib on cholangiocarcinoma through immune regulation, which may be related to the tumor angiogenesis factor effect of M2 macrophage.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer. Despite previous research on immune mechanisms and related molecules in LUAD, the specific regulatory mechanisms of these molecules in the immune microenvironment remain unclear. Furthermore, the impact of regulatory genes or RNA on LUAD metastasis and survival time is yet to be understood. To address these gaps, we collected a substantial amount of data, including 17,226 gene expression profiles from 1,018 samples, 370,640 methylation sites from 461 samples, and 248 miRNAs from 513 samples. Our aim was to explore the genes, miRNAs, and methylation sites associated with LUAD progression. Leveraging the regulatory functions of miRNAs and methylation sites, we identified target and regulated genes. Through the utilization of LASSO and survival analysis, we pinpointed 22 key genes that play pivotal roles in the immune regulatory mechanism of LUAD. Notably, the expression levels of these 22 genes demonstrated significant discriminatory power in predicting LUAD patient survival time. Additionally, our deep learning model accurately predicted distant metastasis in LUAD patients using the expression levels of these genes. Further pathway enrichment analysis revealed that these 22 genes are significantly enriched in pathways closely linked to LUAD progression. Through Immune Infiltration Assay, we observed that T cell CD4 memory resting, monocytes, and macrophages.M2 were the three most abundant cell types in the immune microenvironment of LUAD. These cells are known to play crucial roles in tumor growth, invasion, and metastasis. Single-cell data analysis further validated the functional significance of these genes, indicating their involvement not only in immune cells but also in epithelial cells, showcasing significant differential expression. Overall, this study sheds light on the regulatory mechanisms underlying the immune microenvironment of LUAD by identifying key genes associated with LUAD progression. The findings provide insights into potential prognostic markers and therapeutic targets.

Mucosal-associated invariant T (MAIT) cells have been described in liver and non-liver diseases, and they have been ascribed antimicrobial, immune regulatory, protective, and pathogenic roles. The goals of this review are to describe their biological properties, indicate their involvement in chronic liver disease, and encourage investigations that clarify their actions and therapeutic implications. English abstracts were identified in PubMed by multiple search terms, and bibliographies were developed. MAIT cells are activated by restricted non-peptides of limited diversity and by multiple inflammatory cytokines. Diverse pro-inflammatory, anti-inflammatory, and immune regulatory cytokines are released; infected cells are eliminated; and memory cells emerge. Circulating MAIT cells are hyper-activated, immune exhausted, dysfunctional, and depleted in chronic liver disease. This phenotype lacks disease-specificity, and it does not predict the biological effects. MAIT cells have presumed protective actions in chronic viral hepatitis, alcoholic hepatitis, non-alcoholic fatty liver disease, primary sclerosing cholangitis, and decompensated cirrhosis. They have pathogenic and pro-fibrotic actions in autoimmune hepatitis and mixed actions in primary biliary cholangitis. Local factors in the hepatic microenvironment (cytokines, bile acids, gut-derived bacterial antigens, and metabolic by-products) may modulate their response in individual diseases. Investigational manipulations of function are warranted to establish an association with disease severity and outcome. In conclusion, MAIT cells constitute a disease-nonspecific, immune response to chronic liver inflammation and infection. Their pathological role has been deduced from their deficiencies during active liver disease, and future investigations must clarify this role, link it to outcome, and explore therapeutic interventions.

Immune thrombocytopenia (ITP) is an autoimmune-mediated disease characterized by decreased platelet counts. Cytokines play important roles in modulating the immune response and are involved in the pathogenesis of many autoimmune diseases. This study aimed at exploring the serum levels of a core set of cytokines that exert immune-regulatory functions in newly diagnosed ITP patients (both before and after treatment) and splenectomized ITP patients. Using the Bio-Plex suspension array system and ELISA, the serum levels of IL-10, IL-21, IL-27, IL-33, IL-35, IL-37, and TGF-β1 were detected. The data showed that the serum levels of the immune regulatory cytokines IL-10, IL-35, and TGF-β1 were significantly lower in newly diagnosed ITP patients. Decreased cytokine levels could be improved in patients with a complete response or a response after steroid-based treatment(s). The serum concentrations of TGF-β1 were positively correlated with the platelet counts both before and after treatment. All the detected immune-regulatory cytokines, except IL-37, showed significantly higher levels in splenectomized ITP patients than pretreatment ITP patients and healthy controls. In conclusion, these data suggest that lower levels of immune-regulatory cytokines are involved in the pathogenesis of ITP and that there is a long-lasting overexpression of immune-regulatory cytokines in ITP patients with splenectomy.

OBJECTIVE: Autoimmune diseases are a heterogeneous group of diseases which lose the immunological tolerance to self-antigens. It is well recognized that irregularly provoked T cells participate in the pathological immune responses. As a novel nanomaterial with promising applications, tetrahedral framework nucleic acid (TFNA) nanostructure was found to have immune regulatory effects on T cells in this study.
METHODS: To verify the successful fabrication of TFNA, the morphology of TFNA was observed by atomic force microscopy (AFM) and dynamic light scattering. The regulatory effect of TFNA was evaluated by flow cytometry after cocultured with CD3+ T cells isolated from healthy donors. Moreover, the associated signaling pathways were investigated. Finally, we verified our results on the T cells from patients with neuromyelitis optica spectrum disorder (NMOSD), which is a typical autoimmune disease induced by T cells.
RESULTS: We revealed the alternative regulatory functions of TFNA in human primary T cells with steady status via the JNK signaling pathway. Moreover, by inhibiting both JNK and ERK phosphorylation, TFNA exhibited significant suppressive effects on IFNγ secretion from provoking T cells without affecting TNF secretion. Similar immune regulatory effects of TFNA were also observed in autoreactive T cells from patients with NMOSD.
CONCLUSIONS: Overall, our results revealed a potential application of TFNA in regulating the adaptive immune system, as well as shed a light on the treatment of T cell-mediated autoimmune diseases.

Major depressive disorder (MDD) is a common, severe and disabling neuropsychiatric disorder with a heterogenous etiology. Among the most widely recognized etiological models, immunopathogenesis is a predominant one. Numerous studies have demonstrated aberrant levels of inflammatory markers in the peripheral blood, cerebrospinal fluid (CSF) and brain of patients with MDD. Multiple studies including meta-analyses have reported increased peripheral levels of acute phase proteins, and pro-inflammatory cytokines, particularly IL-1β, TNF-α, and IL-6 in MDD. Postmortem brain studies similarly demonstrated upregulated expressions of these pro-inflammatory cytokines. This along with evidence of monocytic, lymphocytic and microglial activation, suggest an activated inflammatory response system (IRS) in MDD. A few studies show increased levels of anti-inflammatory cytokines or defective inflammatory pathways and a deficit in T cell maturation and responses in MDD patients. This suggests the presence of a Compensatory Immune Response System (CIRS), which can counterbalance the effects of IRS in major depression. More recently, simultaneously increased levels of both the pro-and anti-inflammatory cytokines are reported in the brain of MDD patients; this indicates activity of both the IRS and CIRS in MDD. The IRS and CIRS are the evolutionarily conserved and integral elements of an overarching system. The relevance of a dysregulated IRS-CIRS system in the neurobiological construct of MDD is just beginning to be understood. Speculation is rife that the disrupted IRS-CIRS elements might determine the onset, episodes, neuroprogressive processes, treatment response as well as recovery of patients with MDD. Notably, the signatures of an activated IRS-CIRS might emerge as potential biomarkers of MDD. Herein, an attempt has been made to highlight the biology and pathobiological relevance of IRS-CIRS activation in MDD and provide an insight into the role of these components in pharmacological therapy.

The outbreak of coronavirus disease 2019 (COVID-19) pandemic is quickly spreading all over the world. This virus, which is called SARS-CoV-2, has infected tens of thousands of people. Based on symptoms, the pathogenesis of acute respiratory illness is responsible for highly homogenous coronaviruses as well as other pathogens. Evidence suggests that high inflammation rates, oxidation, and overwhelming immune response probably contribute to pathology of COVID-19. COVID-19 causes cytokine storm, which subsequently leads to acute respiratory distress syndrome (ARDS), often ending up in the death of patients. Mesenchymal stem cells (MSCs) are multipotential stem cells that are recognized via self-renewal capacity, generation of clonal populations, and multilineage differentiation. MSCs are present in nearly all tissues of the body, playing an essential role in repair and generation of tissues. Furthermore, MSCs have broad immunoregulatory properties through the interaction of immune cells in both innate and adaptive immune systems, leading to immunosuppression of many effector activities. MSCs can reduce the cytokine storm produced by coronavirus infection. In a number of studies, the administration of these cells has been beneficial for COVID-19 patients. Also, MSCs may be able to improve pulmonary fibrosis and lung function. In this review, we will review the newest research findings regarding MSC-based immunomodulation in patients with COVID-19.