Regulatory T cells (Tregs) are the principal immune cells that exert anti-inflammatory effects within the organism. Their exosomes exhibit therapeutic efficacy across a broad spectrum of diseases owing to their high stability, low immunogenicity, and substantial penetration capacity. Recent research have indicated that isoallolithocholic acid (isoalloLCA), a metabolite associated with bile acid metabolism, may enhance Treg activity by upregulating forkhead box protein3 (Foxp3) expression. Hence, metabolite-based strategies for reinforcing Tregs may offer novel intervention options for treating related diseases. In this study, tumor necrosis factor (TNF)-α and dextran sulfate sodium (DSS) were employed to establish cellular and animal models of inflammatory bowel disease (IBD), further evaluating the therapeutic efficacy of isoalloLCA-intervened regulatory T cell exosomes (isoalloLCA-Exo) within this model. Our findings demonstrated that isoalloLCA-Exo effectively inhibit colitis progression in a murine model, as indicated by reduced inflammation, decreased apoptosis of intestinal epithelial cells, and improved intestinal barrier function. Furthermore, in vitro analyses elucidated the molecular mechanisms underlying the anti-inflammatory effects of isoalloLCA-Exo, revealing that the intervention effectively reversed TNF-α-induced inflammation and apoptosis in intestinal epithelial cells by modulating the NF-κB pathway. In conclusion, isoalloLCA-Exo can decelerate inflammatory bowel disease progression and suppress inflammatory response in intestinal epithelial cells by inhibiting NF-κB pathway. Notably, isoalloLCA-Exo exhibit superior efficacy to the traditional drug mesalazine and conventional treg exosome(NC-Exo). These findings have significant implications for optimizing Treg-derived exosome-based therapies for inflammation-related diseases.

Previous trials have revealed better treatment efficacy of programmed cell death 1 (PD-1) inhibitors combined with chemotherapy as first-line treatments than chemotherapy alone in advanced gastric cancer (GC) patients, but real-world evidence is still lacking. Hence, this real-world study aimed to investigate the efficacy and safety of PD-1 inhibitors plus chemotherapy as first-line treatments compared with chemotherapy alone in advanced GC patients.

This retrospective cohort study evaluated the efficacy and safety of telitacicept combined with standard therapy in class III-V lupus nephritis (LN).

Melanoma, known for its aggressive behavior and tendency to metastasize to the brain and lungs, is a formidable challenge in oncology. Radiotherapy is a potent treatment for localized solid tumors, effective against both intracranial and extracranial metastases. Yet, some melanoma patients exhibit substantial resistance to radiotherapy, with the underlying mechanisms of this resistance remaining elusive. While radiotherapy can stimulate the infiltration of immune cells, thereby triggering a range of immunostimulatory effects, it can also suppress the tumor microenvironment (TME), limiting its effectiveness. In physiological conditions, cytokines inhibit the activity of immunosuppressive cells through paracrine and autocrine signaling, while also activating immune cells to boost antitumor responses. Here, we found that Interleukin (IL)-21 expression was higher in the mice with good radiotherapy response to melanoma than in the mice with poor radiotherapy response. Interestingly, we also observed the higher infiltration of M2 TAMs and lower CD8 T cells in the group with poor radiotherapy response. To tackle this issue, we explored the therapeutic potential of a plasmid encoding IL-21, delivered via attenuated Salmonella, in mice bearing melanomas. Our findings revealed that IL-21 administration significantly reduced M2 TAMs infiltration and enhanced CD8 T cells infiltration and granzyme B (GZMB) expression within melanoma tumors. Most importantly, the combination of IL-21 with radiotherapy led to markedly tumor reduction compared to either treatment alone. This research highlights the potential of IL-21 as a valuable adjunct to radiotherapy in the treatment of melanoma, presenting a promising strategy for enhancing antitumor immune responses and optimizing patient outcomes.

Renal tubular interstitial inflammation is a central driver of the pathogenesis of diabetic kidney disease (DKD). Peroxisome proliferator-activated receptor alpha (PPARα), predominantly expressed in renal tubular epithelial cells (TECs), plays a key role in regulating inflammation. However, the precise molecular mechanisms through which PPARα exerts its protective effects in DKD remain unclear.

Crohn's disease (CD) is a chronic inflammatory disorder that can affect any part of the gastrointestinal tract, with the exact etiology remaining unclear. Recent studies have implicated the role of human antigen R (HuR) in the pathogenesis of various inflammatory diseases, including CD. However, the role of HuR in the modulation of CD remains underexplored. Therefore, this study aimed to investigate the mechanistic involvement of HuR in CD.

Microglia-mediated neuroinflammation plays a critical role in myelin loss in multiple sclerosis (MS). Baicalin (BAI) and kaempferol (KAE) are known for their potent anti-inflammatory properties; however, their potential to alleviate demyelination and treat MS has rarely been rarely investigated.

Myelofibrosis (MF) is the most common complication of myeloproliferative neoplasms (MPNs)，which is markedly correlated with a dismal prognosis. Murine model such as the thrombopoietin receptor (MPL)W515L-mutant MPN mouse model functions as a crucial vehicle in disease research, is widely used in basic and applied research on MPNs and MF.However, the lack of methods for dynamic observation of MF progression hinders mechanistic studies and drug development for MF. Here we develop a sensitive, stable and minimally invasive MPN evaluation system to assess the evolution of myelofibrosis in murine model.Key peripheral blood parameters (WBC, RBC, HGB, HCT, PLT, and tumor cell proportion) from MPN mice were analyzed using PCA to reduce dimensionality and generate a comprehensive evaluation score (Y). Based on peripheral blood smear observations and predefined score cut-off values (0.59 and - 0.44), MPN was classified into mild, moderate, and severe stages. Validation conducted across diverse experimental settings yielded outcomes that were in alignment with the pathological grading of myelofibrosis. This system facilitated the dynamic monitoring of MF progression in applied research on pigment epithelium-derived factor treatment for MPN and basic studies on the role of NLRP inflammasomes in the bone marrow microenvironment. We believed that this minimally invasive evaluation system for grading MF severity in MPN mouse model will provide a potential tool for MPN pathogenesis research and targeted therapy development.

Acute lung injury (ALI) is a serious disease characterized by inflammatory reaction, lung tissue hyperemia and edema. Rebaudioside B (Reb B) is a natural sweetener extracted from Stevia Rebaudiana and has a variety of pharmacological activities. The purpose of this study was to investigate the protective effect of Reb B on ALI and its potential mechanism. The protein-protein interaction network, GO and KEGG were all used to determine the mechanism of Reb B in the treatment of ALI. Finally, we established a rat ALI model that was induced by oleic acid, and further verified the protective effect of Reb B on injured lung tissue as well as its underlying mechanism through a variety of experimental methods. 1481 potential targets of Reb B were identified through the database, and 136 communication targets were found between Reb B and ALI. In vivo experiments show that the protective effect of Reb B on ALI in rats is achieved by reducing related histopathological changes, the release of inflammatory factors, etc. In summary, we have preliminarily revealed the protective effect of Reb B on ALI and its possible mechanisms through research on network pharmacology and in vivo experiments.

Chronic sleep deprivation (CSD) is increasingly common in modern society and is linked to various diseases, including autoimmune conditions like experimental autoimmune uveitis (EAU), a severe ocular inflammation. The pathogenesis of EAU remains unclear, but poor sleep quality has been shown to exacerbate inflammation through immune modulation. To explore this relationship, we conducted a clinical study at the Ophthalmology Center of Renmin Hospital of Wuhan University (July 2023-July 2024), assessing sleep quality in uveitis patients using the Pittsburgh Sleep Quality Index (PSQI). Based on PSQI scores, patients were categorized into four groups, and their symptoms and characteristics were recorded. Simultaneously, a B10.RIII mouse model of CSD and EAU was developed. Western blotting assessed the phosphorylation of Signal Transducer and Activator of Transcription 1 (STAT1) and the expression of Interferon-Stimulated Gene 15 (ISG15) expression, while immunofluorescence and western blotting evaluated macrophage activity and cytokine secretion. Clinical results showed a strong correlation between poor sleep quality and worsened inflammatory symptoms. In mice, CSD increased STAT1 phosphorylation and ISG15 expression, enhancing macrophage activity and worsening ocular inflammation. Our findings suggest that CSD exacerbates EAU through STAT1 phosphorylation, ISG15 expression, and macrophage activation. The clinical data further support this mechanism, indicating that improving sleep quality could reduce the risk of autoimmune diseases and offering new insights into the connection between sleep and immune function.

A pseudo-allergic reaction is an abrupt, IgE-independent reaction that is similar to an allergic reaction. Sea Buckthorn leaves (SBL) have been extensively researched for their pharmacological benefits, including immunological modulation, anti-inflammatory and anti-tumor properties. However, at present, its anti-pseudo-allergic effect are remains to be assessed. In this work, the therapeutic impact and mechanism of SBL extract and its active monomer gallic acid (GA) on pseudo-allergic reaction were studied. A total of 61 SBL extract components were identified using UPLC-Q-Exactive-Orbitrap-MS and HPLC, of which the main component GA was 16.73 ± 0.30 mg/g. GA was identified as the primary active ingredient in SBL extract through hyaluronidase inhibition experiments and molecular docking techniques. It was found that SBL extract and GA reduced capillary dilatation and the rate of paw swelling and Evans blue exudation in C48/80-induced passive cutaneous anaphylaxis (PCA). In C48/80-induced mice systemic allergy model, SBL extract and GA were observed to reverse the reduction in body temperature and block the release of allergic mediators histamine and inflammatory factors TNF-α, CCL2, and IL-6. Using the C48/80-induced RBL-2H3 cells model, it was further demonstrated that SBL extract and GA prevented RBL-2H3 cells activation in vitro, which lowered the release of allergy mediators histamine and β-hexosaminidase as well as inflammatory factors TNF-α, CCL2, and IL-6. SBL extract and GA also reduced intracellular Ca concentration. Furthermore, the phosphorylation levels of PLC γ1 and IP3 could be downregulated by SBL extract and GA. To sum up, SBL extract and GA reduced pseudo-allergic reactions brought on by C48/80 and are anticipated to be created as novel medications to treat pseudo-allergic reactions.

To investigate antibody prevalence and long-term seizure outcomes in epilepsy patients with suspected autoimmune etiology but without any signs of autoimmune encephalitis (AE), and to compare the performance of Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score and Antibodies Contributing to Focal Epilepsy Signs and Symptoms (ACES) score.

Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide, with a dismal 5-year survival rate. New drugs targeting pancreatic ductal adenocarcinoma (PDAC), the primary pathological subtype, are urgently needed. LAQ824, a novel pan-histone deacetylase inhibitor (HDACi), has shown anti-tumor activity in various cancers, but its effects on PDAC remain unexplored. This study investigates the therapeutic potential of LAQ824 in PDAC and its role in modulating immune escape mechanisms. Using a subcutaneous tumor model in C57BL/6 J mice, LAQ824's anti-tumor effects were evaluated. In vitro and in vivo experiments-including IHC, flow cytometry, RNA sequencing, and single-cell RNA sequencing-demonstrated that LAQ824 inhibits tumor proliferation, suppresses the epithelial-mesenchymal transition (EMT), and induces apoptosis. LAQ824 also enhances immunogenicity by upregulating MHC-I-mediated antigen presentation, increasing immune cell infiltration, and promoting CD8 T cell maturation and differentiation. Mechanistically, LAQ824 upregulated MHC-I expression by enhancing chromatin accessibility of related genes, with HDAC1 identified as a key repressor of MHC-I in PDAC cells. In conclusion, we found that LAQ824 has a significant anti-tumor effect in PDAC. LAQ824 not only directly affects general biological behaviors such as proliferation, apoptosis, and EMT, but also increases the immunogenicity of tumor cells by upregulating the expression of MHC-I in PDAC, which promotes the antigen presentation process and enhances anti-tumor immunity. By showcasing LAQ824's potential as a therapeutic target against PDAC, the present study provides novel insights into the link between epigenetic regulation and immunogenicity in PDAC.

Acute respiratory distress syndrome (ARDS) is the most common respiratory emergency and one of the most severe clinical syndromes. Bacterial and viral infections are the frequent etiological factors. Pseudomonas aeruginosa (PA) is the most significant gram-negative pathogen associated with pneumonia and ARDS in critically ill patients with respiratory diseases. However, multi-drug resistance and biofilm formation pose significant challenges to the clinical treatment of PA-associated pulmonary infections. In this study, we focused on edaravone (EDA), a brain-protective agent and free-radical scavenger commonly used in neurology, and examined its role in PA-ALI. We found EDA significantly mitigated pulmonary pathological damage, inflammatory responses and Reactive Oxygen Species (ROS) generation induced by PA in vivo. The in-vitro assays revealed EDA inhibited the transcription and secretion of pro-inflammatory factors induced by PA in RAW264.7 cells by targeting the TLR4/MyD88/NF-κB signaling pathways. Additionally, EDA reduced the production of intracellular ROS and cell death. EDA treatment enhanced the transcription of antimicrobial peptides, including defensin beta 1 (Defb1), defensin beta 2 (Defb2), CC motif chemokine ligand 20 (Ccl20), secretory leukocyte peptidase inhibitor (Slpi), and lactotransferrin (Ltf), with a significant upregulation of Defb1 expression. We also explored the role of EDA in lung endogenous stem cells using Sftpc-DreER; Scgb1a1-CreER; R26-TLR mice. Our findings indicated that EDA promoted the regeneration of club cells in response to PA stimulation by promoting their proliferation. And also, EDA inhibited PA infection induced cell apoptosis in lung tissues. In conclusion, EDA acts as a protective agent in PA-ALI. It not only inhibits inflammatory responses induced by PA but also enhances the expression of antimicrobial peptides and promotes club cell regeneration. Therefore, EDA may serve as an adjunctive treatment for PA-ARDS.

Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI) and can progress to acute liver failure (ALF). Hepatocyte death is widely recognized as the central event in APAP-induced liver injury; however, the underlying mechanisms are complex and not yet fully elucidated. Ferroptosis, a recently identified form of programmed cell death characterized by glutathione (GSH) depletion and disruption of cellular redox homeostasis, shares key features with APAP-induced hepatotoxicity. This study aimed to investigate the role of ferroptosis in APAP-induced liver injury and to explore potential therapeutic targets.

Mitochondria, known as the powerhouse of cells, play a crucial role in host innate immunity during flavivirus infections such as Dengue, Zika, West Nile, and Japanese Encephalitis Virus. Mitochondrial antiviral signaling protein (MAVS) resides on the outer mitochondrial membrane which is triggered by viral RNA recognition by RIG-I-like receptors (RLRs). This activation induces IRF3 and NF-κB signaling, resulting in type I interferon (IFN) production and antiviral responses. Upon flavivirus infection, mitochondrial stress and dysfunction may lead to the release of mitochondrial DNA (mtDNA) into the cytoplasm, which serves as a damage-associated molecular pattern (DAMP). Cytosolic mtDNA is sensed by cGAS (cyclic GMP-AMP synthase), leading to the activation of the STING (Stimulator of Interferon Genes) pathway to increase IFN production and expand inflammation. Flaviviral proteins control mitochondrial morphology by controlling mitochondrial fission (MF) and fusion (MFu), disrupting mitochondrial dynamics (MD) to inhibit MAVS signaling and immune evasion. Flaviviral proteins also cause oxidative stress, resulting in the overproduction of reactive oxygen species (ROS), which triggers NLRP3 inflammasome activation and amplifies inflammation. Additionally, flaviviruses drive metabolic reprogramming by shifting host cell metabolism from oxidative phosphorylation (OxPhos) to glycolysis and fatty acid synthesis, creating a pro-replicative environment that supports viral replication and persistence. Thus, the present review explores the complex interaction between MAVS, mtDNA, and the cGAS-STING pathway, which is key to the innate immune response against flavivirus infections. Understanding these mechanisms opens new avenues in therapeutic interventions in targeting mitochondrial pathways to enhance antiviral immunity and mitigate viral infection.

Cancer-related deaths continue to rise, largely due to the suboptimal efficacy of current treatments. Fortunately, immunotherapy has emerged as a promising alternative, offering new hope for cancer patients. Among various immunotherapy approaches, targeting tumor-specific antigens (TSAs) has gained particular attention due to its demonstrated success in clinical settings. Despite these advancements, there are still gaps in our understanding of TSAs. Therefore, this review explores the life cycle of TSAs in cancer, the methods used to identify them, and recent advances in TSAs-targeted cancer therapies. Enhancing medical professionals' understanding of TSAs will help facilitate the development of more effective TSAs-based cancer treatments.

Myocarditis is one of the common causes of sudden death in adolescents, and autoimmune response and inflammation play an essential role in the development of myocarditis. Quercetin is a natural flavonoid compound with anti-inflammatory and cardioprotective effects. However, the mechanism of quercetin in autoimmune myocarditis remains unclear. This study observed that quercetin significantly improved cardiac function, inflammation and fibrosis in mice with experimental autoimmune myocarditis (EAM). In addition, Network pharmacology predicts the key target C/EBPβ and signalling pathway MAPK for quercetin treatment of autoimmune myocarditis. CESTA and DARTS experiments verified that quercetin and C/EBPβ have strong binding ability. It is shown that quercetin down-regulates MCP-1 expression in H9C2 cells by dephosphorylation of ERK1/2 and C/EBPβ. Specifically, quercetin reduced the binding of C/EBPβ to the MCP-1 promoter, resulting in decreased expression of MCP-1, which was associated with decreased ERK1/2 dependent phosphorylation at the C/EBPβ threonine 188 site. This inhibitory effect of quercetin could be further enhanced by the ERK1/2 inhibitor PD98059. The biological relevance of this regulatory network is demonstrated in EAM mice. In conclusion, these results illustrate the protective effect of quercetin against autoimmune myocarditis. A novel regulatory mechanism was revealed, namely the down-regulation of MCP-1 through the ERK1/2-C/EBPβ axis. This provides a new therapeutic strategy for autoimmune myocarditis.

Insulin-like peptide 3 (INSL3) is a small peptide hormone produced almost exclusively by testicular Leydig cells in males and thus serves as an essential biomarker of the maturation and functionality of these cells. Accumulated evidence suggests that INSL3 is a crucial factor affecting testicular descent during fetal development by regulating the growth of the gubernaculum. However, the physiological roles of INSL3 in adults remain unclear. Here, we reported that relaxin family peptide 2 (RXFP2), the receptor of INSL3, is expressed on macrophages, and treatment with INSL3 can promote M2 macrophage polarization via the Akt/mTOR/S6K and PKA/CREB pathways. In addition, INSL3 can inhibit macrophage phagocytosis and promote their migration via the Epac and PKA signaling pathways, respectively. These findings reveal a new role for INSL3 in regulating macrophage function and shed new light on our understanding of the role of INSL3 in adulthood.

Regulated cell death (RCD), a genetically controlled process mediated by specialized molecular pathways (commonly termed programmed cell death), plays pivotal roles in diverse pathophysiological processes. However, the landscape and functional implications of RCD subtypes in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly characterized. This study aimed to systematically investigate the involvement of RCD mechanisms in the pathogenesis and progression of CRSwNP.

Compared to other HCC, those related to MAFLD exhibit distinct prognostic differences. This article aims to elucidate the impact of MAFLD on HCC prognosis through the lens of KIF20A, thereby providing a theoretical foundation for targeted therapies in MAFLD-related HCC.