Mediators Of Inflammation[JOURNAL]
Sun
200 papers
Epithelial Gab1 Restricts Sepsis-Induced Intestinal Injury by Orchestrating TNF/NF-κB Axis.
Jin W, Wu Y, Cheng X … +5 more , Pan Y, He L, Xu Y, Xu J, Zhang X
Mediators Inflamm · 2026 · PMID 41624377 · Full text
A series of intestine-related alterations have been considered a key factor in triggering sepsis, with increased apoptosis of intestinal epithelial cells (IECs) notably contributing to this process. Compromised gut barri...
A series of intestine-related alterations have been considered a key factor in triggering sepsis, with increased apoptosis of intestinal epithelial cells (IECs) notably contributing to this process. Compromised gut barrier due to IEC apoptosis promotes bacterial translocation and inflammatory responses, which in turn escalates to further IEC death and barrier defects. Nevertheless, the precise mechanisms that safeguard IECs from apoptosis and interrupt this vicious cycle are yet to be elucidated. Here, we report that Grb2-associated binder 1 (Gab1) expression is diminished in the intestines of both septic patients and established sepsis models. Epithelial Gab1 deficiency rendered mice susceptible to lipopolysaccharide (LPS)-induced sepsis by sensitizing IECs to apoptosis, thereby contributing to systemic inflammation and markedly exacerbating septic lethality. Mechanistically, Gab1 mitigated apoptotic signaling via IKKβ-dependent NF-κB activation and subsequent transcriptional regulation of apoptotic genes in response to TNF-α. Collectively, our findings define a protective role for Gab1 in sepsis-induced intestinal injury by sustaining apoptotic balance and intestinal homeostasis, which provides new insights into therapeutic strategies for sepsis management, particularly those aiming at restoring immune homeostasis and improving barrier function.
Identification of Treatment Targets in Allergic Conjunctivitis Through Proteome-Scale Mendelian Randomization Analysis.
Li H, Zhang Y, Shang Y … +3 more , Dai J, Ji S, Wu K
Mediators Inflamm · 2026 · PMID 41624376 · Full text
PURPOSE: Allergic conjunctivitis (AC) is a condition with a rising prevalence that occasionally leads to irreversible visual impairment. However, few novel therapeutic targets have been identified for AC. The investigati...
PURPOSE: Allergic conjunctivitis (AC) is a condition with a rising prevalence that occasionally leads to irreversible visual impairment. However, few novel therapeutic targets have been identified for AC. The investigation aims to utilize the Mendelian randomization (MR) technique to explore the causal impacts exerted by the plasma proteome on AC. METHODS: An evaluation was conducted on a two-sample MR study utilizing 2,940 plasma proteins from the UK Biobank Pharma Proteomics Project (UKB-PPP) to investigate their causal links with AC. Confirmation of these MR results was achieved using Summary-data-based MR (SMR) and Bayesian colocalization techniques. Moreover, evaluations concerning the druggability of proteins, interactions among proteins, and phenome-wide MR (Phe-MR) studies were conducted to ascertain the functionalities of the identified proteins implicated in causality. RESULTS: MR analysis identified five circulating proteins (TLR1, ING1, RALY, CSF2, and ITGAM) whose genetically predicted plasma levels were significantly associated with AC risk ( < 0.05). Functional enrichment analysis of the identified proteins revealed statistically significant biologically relevant pathways, including macrophage activation and pathways of plasma membrane signaling receptor complex, suggesting underlying immune and receptor-mediated mechanisms in AC. SMR and HEIDI validation supports four (TLR1, ING1, ITGAM, and CSF2) of five MR-identified proteins as causal candidates for AC. Subsequent colocalization analysis provided further support for two credible proteins (ING1 and CSF2). Protein druggability suggests CSF2 and ING1 as novel and potentially druggable candidates for AC. CONCLUSIONS: Our research identified proteins that appear to have causal effects and could serve as potential therapeutic targets for AC.
Bidirectional Regulation of NLRP3 Inflammasome and Mitochondrial Quality Control in Sepsis: Mechanisms and Therapeutic Implications.
Liao X, Wang Y, Zhang Z … +2 more , Qu X, Zhou G
Mediators Inflamm · 2026 · PMID 41613015 · Full text
Characterized by its capacity to induce organ failure, sepsis constitutes a life-threatening pathological state with high incidence and mortality rates. Current treatments primarily focus on antimicrobial therapy and org...
Characterized by its capacity to induce organ failure, sepsis constitutes a life-threatening pathological state with high incidence and mortality rates. Current treatments primarily focus on antimicrobial therapy and organ support, lacking direct interventions targeting the restoration of cellular or organelle function. Among these mechanisms, mitochondrial dysfunction and overactivation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome stand out as key pathological hallmarks. As a classic inflammasome, the NLRP3 inflammasome, upon activation, drives cellular pyroptosis and massive release of inflammatory mediators. Beyond their role as cellular energy generators, mitochondria participate in the modulation of inflammatory responses and oxidative stress control. Mitochondrial quality control (MQC) serves as a prerequisite for the orderly performance of mitochondrial physiological functions. Disruption of MQC invariably results in mitochondrial dysfunction, triggering liberation of mitochondrial reactive oxygen species (mtROS) along with mitochondrial damage-associated molecular patterns (mtDAMPs), which serve as direct triggers for NLRP3 inflammasome formation and stimulation. This process disrupts MQC, exacerbates mitochondrial dysfunction, and forms a mutually reinforcing "MQC imbalance-NLRP3 overactivation" vicious cycle that drives disease progression. This review aims to: (1) systematically elucidate the complex bidirectional regulatory mechanisms between the NLRP3 inflammasome and MQC in the context of sepsis, (2) summarize the latest research progress on targeted intervention strategies based on this vicious cycle, and (3) discuss the challenges in clinical translation and future directions of these strategies.
FT3 Levels and Systemic Inflammation: Evidence From a Population-Based NHANES Analysis.
Yang L, Wang HY, Fu MF … +4 more , Zhang YH, Chen X, Wang ZX, Sun H
Mediators Inflamm · 2026 · PMID 41608316 · Full text
OBJECTIVE: Previous studies suggest a complex interaction between 3,3',5-triiodo-L-thyronine (T3) and inflammation, but this relationship remains unclear. This study investigates the association between free triiodothyro...
OBJECTIVE: Previous studies suggest a complex interaction between 3,3',5-triiodo-L-thyronine (T3) and inflammation, but this relationship remains unclear. This study investigates the association between free triiodothyronine (FT3) levels and inflammatory markers in the US population using National Health and Nutrition Examination Survey (NHANES) data. METHODS: This study analyzed NHANES data from three cycles between 2007 and 2012, using Spearman correlation tests and multivariate linear regression. Subgroup analyses and interaction tests were conducted based on age, gender, race, body mass index (BMI), thyroid-stimulating hormone, and free thyroxine (T4) to determine the correlations between FT3 and seven systemic inflammatory markers: C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-white blood cell ratio (PWR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). RESULTS: A total of 2306 participants were included in this study. Univariate correlation analysis showed that CRP, NLR, MLR, and PLR were significantly negatively correlated with FT3 levels (all < 0.05). After adjusting for confounders, FT3 levels were significantly negatively associated with CRP, NLR, and PLR (all < 0.05). Subgroup analysis showed that age significantly modified the associations between FT3 and systemic inflammatory markers, such as CRP, NLR, MLR, SII, and SIRI (-interaction < 0.05). The inverse associations were more consistent among individuals aged ≥ 65 years. CONCLUSION: In the general population, FT3 levels exhibit inverse associations with systemic inflammatory markers.
Research Progress on Bioactive Components Regulating P-Selectin for Microcirculatory Improvement: Potential Implications in Acute Pancreatitis.
Liu Y, Ao X, Hao W … +7 more , Wang H, Li L, Wang S, Li J, Liu J, Zhou X, Li Z
Mediators Inflamm · 2026 · PMID 41583122 · Full text
Severe acute pancreatitis (SAP) is associated with high morbidity and mortality. Microcirculatory dysfunction is a critical pathological event in this process and a primary contributor to organ failure (OF). Despite the...
Severe acute pancreatitis (SAP) is associated with high morbidity and mortality. Microcirculatory dysfunction is a critical pathological event in this process and a primary contributor to organ failure (OF). Despite the pivotal role of P-selectin in mediating the adhesion of activated platelets and leukocytes to the vascular endothelium, a process central to microcirculatory dysfunction, effective therapeutic interventions for SAP remain limited. , a traditional Chinese medicinal (TCM) herb, possesses well-documented pharmacological properties, including anti-inflammatory, anticoagulant, and microcirculation-improving effects. This review synthesizes recent advances in understanding the bioactive components of , which ameliorate microcirculation by modulating P-selectin expression and activity through mechanisms targeting its transcription, translation, or post-translational activation. Given the current lack of direct evidence in the context of SAP, we synthesized extensive findings from studies on cardiovascular, gastrointestinal, and inflammatory diseases, as well as from relevant acute pancreatitis (AP)/SAP models. These collective data demonstrate that effectively inhibits platelet aggregation, attenuates leukocyte adhesion, mitigates endothelial injury, and improves perfusion. Substantial evidence suggests that the bioactive compounds derived from function as effective agents against microcirculatory dysfunction by targeting P-selectin. Leveraging this well-defined mechanistic pathway and the promising therapeutic efficacy observed in AP/SAP models, targeting P-selectin with 's bioactive compounds emerges as a compelling novel strategy for SAP-associated microcirculatory dysfunction, laying a groundwork for subsequent validation studies.
After Traumatic Brain Injury, EPHA4 Enhances Endoplasmic Reticulum Stress to Promote M1 Microglial Polarization Through the MAPK Signaling Pathway.
Tan Y, Xia J, Liu M … +3 more , Deng S, Wu H, Qian C
Mediators Inflamm · 2026 · PMID 41583121 · Full text
BACKGROUND: Traumatic brain injury (TBI) is an important cause of disability and death worldwide. The development of neuroinflammation after TBI is related to the brain parenchyma. M1-type microglia play important roles...
BACKGROUND: Traumatic brain injury (TBI) is an important cause of disability and death worldwide. The development of neuroinflammation after TBI is related to the brain parenchyma. M1-type microglia play important roles in this process, but the specific mechanism through which regulating microglia M1 polarization is still not fully understood. This study aimed to investigate the role of ephrin receptor A4 (EPHA4) in the M1 polarization of microglia after TBI. METHODS: A TBI rat model was established by the controlled cortical impact (CCI) method, and M1 polarization of GMI-R1 cells was induced by lipopolysaccharide (LPS) treatment. Target genes associated with the progression of TBI were screened by transcriptome sequencing; the expression of key genes and proteins was detected by real-time quantitative PCR (RT‒qPCR), Western blot, ELISA, and immunofluorescence, and the damage of the rat brain tissue and the blood-brain barrier (BBB) was evaluated by hematoxylin‒eosin (HE) staining and Evans blue staining. RESULTS: This study revealed that EPHA4 expression is upregulated in the brain tissue of TBI rats and that treatment with its inhibitor, KYL peptide, can improve the progression of TBI. KYL peptide intervention downregulated the levels of the proinflammatory cytokines and upregulated the levels of the anti-inflammatory cytokines and inhibited the M1 polarization of microglia. The levels of the endoplasmic reticulum stress (ERS)-related proteins and Ca were upregulated in TBI rats and downregulated after KYL peptide treatment but subsequently increased after 123C4 treatment. Our results showed that EPHA4 promoted the M1 polarization of microglia by enhancing ERS. Notably, mitogen-activated protein kinase (MAPK) signaling was significantly enriched in TBI. In vitro studies revealed that LPS treatment promoted the activation of MAPK signaling in GMI-R1 cells. A mechanistic study revealed that EPHA4 may activate ERS by activating the MAPK signaling pathway and promote M1 polarization of microglia after TBI. CONCLUSION: Our study revealed that the EPHA4/MAPK axis may be a key regulatory factor in controlling microglial M1 polarization during brain injury. Blocking this signaling axis may represent a potential therapeutic approach for improving TBI.
Nicotine Regulates LPS-Induced Inflammatory Responses in HMC3 Microglia and Exerts Neuronal Protection.
Qin Y, Yan X, Luo Y … +6 more , Wang H, Tian Y, Wu X, Chen H, Hou H, Hu Q
Mediators Inflamm · 2026 · PMID 41583120 · Full text
Microglia-mediated neuroimmune responses have been implicated in central nervous system injury and disease pathogenesis. The α7 nicotinic acetylcholine receptor (α7 nAChR), which is expressed on microglia and participate...
Microglia-mediated neuroimmune responses have been implicated in central nervous system injury and disease pathogenesis. The α7 nicotinic acetylcholine receptor (α7 nAChR), which is expressed on microglia and participates in microenvironment interactions, is a key mediator of the cholinergic anti-inflammatory pathway. Nicotine activates the α7 nAChR, which may mediate the inflammation of microglia. This study aims to explore the modulatory effects of nicotine on neuroinflammation and its potential indirect neuroprotective effects using an in vitro microglial cell inflammation model. In our study, inflammatory phenotype indicators and molecular mechanisms of HMC3 cells were analyzed. Furthermore, an HMC3 microglia-SH-SY5Y neuronal coculture system was constructed to investigate the indirect neuroprotective effects of nicotine. The results demonstrated that nicotine exerted an inhibitory effect on the lipopolysaccharide-induced HMC3 microglia inflammation, promoted the release of neurotrophic factors, and neuronal survival by altering the immune environment. These effects appear to be mediated through the activation of α7 nAChR, leading to an increase in phosphorylation of PI3K. This study provides important insights into the immunomodulatory functions of low-concentration nicotine in the nervous system and contributes to a deeper understanding of its potential therapeutic applications.
Association Between Atopic Dermatitis and Systemic Immune-Inflammation Index: Evidence From NHANES 1999-2006.
Han J, Du G, Guo S … +7 more , Hao J, Wang Y, Li R, Lang X, Zhang Y, Zhu X, Cui H
Mediators Inflamm · 2026 · PMID 41583119 · Full text
BACKGROUND: Clinical studies have demonstrated that the systemic immune-inflammation index (SII) is widely used to assess immunity and inflammation in patients. However, the association between SII and atopic dermatitis...
BACKGROUND: Clinical studies have demonstrated that the systemic immune-inflammation index (SII) is widely used to assess immunity and inflammation in patients. However, the association between SII and atopic dermatitis (AD) remains unclear. This study, based on the National Health and Nutrition Examination Survey (NHANES) database, aims to explore the relationship between SII and AD. METHODS: This study utilized NHANES data from 1999 to 2006, with a total of 8194 subjects included in the final analysis. We examined the associations between AD, SII, and other covariates by analyzing baseline characteristics and performing correlation analyses. Multivariate generalized linear models (GLMs) were used to analyze the correlation between AD and SII risk. A weighted multivariate logistic regression model was applied to examine the association between SII and AD. Additionally, a nomogram was constructed to predict the risk of developing AD. The eXtreme Gradient Boosting (XGBoost) algorithm was employed to evaluate feature importance. Finally, subgroup analysis was performed to further explore the relationship between SII and AD across different subpopulations. RESULTS: Significant differences were observed between the AD and control groups in terms of race, SII, SII group, and other variables. Furthermore, the -values for SII (Q2 and Q3 groups) in all three models were less than 0.05, indicating that the influence of SII on the outcome was not significantly affected by other covariates. The weighted multivariate logistic analysis revealed that SII was strongly associated with AD as a risk factor. The nomogram demonstrated good predictive value for AD, and the XGBoost algorithm further confirmed the high predictive value of SII in AD diagnosis. Finally, subgroup analysis highlighted the significance of the association between SII and specific forms of dermatitis in various subpopulations. CONCLUSION: Elevated SII is independently associated with increased AD risk. Although the cross-sectional design precludes causal inference, SII represents a cost-effective biomarker for AD risk stratification. Critically, emerging evidence positions SII as a predictor of therapeutic response-particularly to JAK inhibitors and biologics-highlighting its dual utility in risk assessment and precision management of AD.
L. Flower Exosome-Like Nanoparticles (RFELNs) Activate AhR/IL-22 to Relieve Intestinal Barrier Dysfunction Through Regulating Gut Microbiota-Interrelated Tryptophan Metabolism in Ulcerative Colitis Mice.
Shen F, Sun K, Song J … +5 more , Chen X, Dai J, Qi Y, Zhang L, Ma L
Mediators Inflamm · 2026 · PMID 41583118 · Full text
BACKGROUND: Intestinal barrier dysfunction is a key driver of ulcerative colitis (UC) recurrence and chronic persistence. Modulating group 3 innate lymphoid cells (ILC3) activity and tryptophan-derived metabolites is cru...
BACKGROUND: Intestinal barrier dysfunction is a key driver of ulcerative colitis (UC) recurrence and chronic persistence. Modulating group 3 innate lymphoid cells (ILC3) activity and tryptophan-derived metabolites is crucial for enhancing mucosal repair in UC. L. flower exosome-like nanoparticles (RFELNs) could ameliorate intestinal mucosal injury in mice. This study aimed to investigate the impact of RFELNs on intestinal barrier repair in UC mice and explore the underlying mechanisms. METHODS: Changes in body weight, food intake, DAI score, colon length, pathological score, and inflammatory factor level were performed to assess the therapeutic effect of RFELNs on DSS-stimulated UC mouse models. The effects of RFELNs on intestinal barrier integrity were assessed by intestinal barrier permeability analysis, Alcian Blue staining, immunohistochemistry (IHC), and western blot assays. IL-22 level was measured by immunofluorescent staining and ELISA assay. Besides, flow cytometry was performed to detect the proportions of ILC3 and NCRILC3 in the colon. Subsequently, an in vitro culture system consisting of NCM460 cells and MNK3 cells was established to determine potential mechanism of RFELNs' influence on UC. RESULTS: RFELNs prominently relieved pathological symptoms in UC mice, including weight loss, enhanced DAI score, shortened colon, and pathological colon damage. Moreover, RFELNs decreased the concentration of FITC-dextran and DAO level and enhanced D-lactate levels. Additionally, RFELNs significantly enhanced the number of colonic goblet cells, restored epithelial tight junctions (TJs), and upregulated TJ protein levels. Moreover, RFELNs enhanced IL-22 expression and the proportion of ILC3 cells and NCRILC3 cells. The protective effect of RFELNs on UC depends on AhR. Further, RFELNs activated AhR pathway by increasing the content of indole derivatives produced by tryptophan metabolism, thus promoting the repair of intestinal barrier damage. CONCLUSION: RFELNs restored intestinal barrier function in UC mice by activating AhR/IL-22 signaling through regulation of gut microbiota-dependent tryptophan metabolism.
Synergistic Alleviation of Inflammatory Cytokine Storms in Sepsis Rats by Low-Intensity Pulsed Ultrasound and Imipenem.
Tang W, Deng J, Zhang X … +10 more , Song G, Qin J, Li C, Xiao X, Wu L, Tang Y, Zhou Y, Li J, He S, Wang Y
Mediators Inflamm · 2026 · PMID 41551210 · Full text
AIMS: This study aimed to investigate the effects of low intensity pulsed ultrasound (LIPUS) combined with imipenem (IMI) on inflammatory responses and organ protection in septic rats. RESULTS: The study involved 230 Spr...
AIMS: This study aimed to investigate the effects of low intensity pulsed ultrasound (LIPUS) combined with imipenem (IMI) on inflammatory responses and organ protection in septic rats. RESULTS: The study involved 230 Sprague-Dawley (SD) rats, with 80 used for survival analysis and 150 for sampling over 72 h. Histological examination (hematoxylin and eosin [H&E] staining) and transmission electron microscopy (TEM) revealed that LIPUS combined with IMI significantly alleviated spleen tissue damage and reduced mitochondrial edema. Key inflammatory cytokines, such as interleukin-1 beta (IL-1), tumor necrosis factor-alpha (TNF-), and IL-6 were significantly decreased, while IL-10 levels increased in the LIPUS + IMI group ( < 0.05). The combined treatment also reduced the expression of cytokines, such as IL-1 receptor (IL-1R), nuclear factor kappa B p65 (NF-B p65), transforming growth factor-beta (TGF-), and high mobility group protein box 1 (HMGB1), indicating a reduction in inflammation ( < 0.05). CONCLUSION AND INNOVATION: This study presents a novel approach by integrating LIPUS with IMI, providing a noninvasive and effective strategy to mitigate cytokine storms, optimize antibiotic use, and reduce organ damage in sepsis. The protective effects observed are primarily attributed to the inhibition of the IL-1R/NF-B signaling pathway, which significantly improves survival outcomes in septic rats. This combined therapy has potential for enhancing sepsis treatment protocols.
Association Between Neutrophil Percentage-Albumin Ratio and Biological Aging in Rheumatoid Arthritis in the United States: A Cross-Sectional Study of NHANES.
Xu Y, Zhao H, Gao Y … +6 more , Zhao L, Han J, Li R, Wu Z, Zhao J, Zhang L
Mediators Inflamm · 2026 · PMID 41551209 · Full text
BACKGROUND: The accelerating process of global aging has made the burden of age-related diseases increasingly severe, and traditional chronological age fails to reflect individual heterogeneity in aging. The neutrophil p...
BACKGROUND: The accelerating process of global aging has made the burden of age-related diseases increasingly severe, and traditional chronological age fails to reflect individual heterogeneity in aging. The neutrophil percentage-to-albumin ratio (NPAR), is a multidimensional health assessment index composed of inflammatory markers (neutrophils) and nutritional markers (albumin) to reflect inflammation and nutritional status, has shown unique potential in rheumatoid arthritis (RA) research. However, its association with biological age (BA; such as Klemera-Doubal method [KDM] age and phenotypic age, PhenoAge) has not yet been systematically validated in RA patients. By evaluating NPAR indicators in patients with RA, this study intends to reveal its value as a potential biomarker for predicting biological aging and its acceleration. METHODS: This study was based on the National Health and Nutrition Survey 1999-2018 cycle database, and a cross-sectional analysis of 1053 adult patients with RA was included. Core variable definitions include: neutrophil-albumin ratio (NPAR) = percentage of neutrophils (%)/albumin (g/dL); BA was calculated by the KDM (including 10 biomarkers) and the PhenoAge algorithm, respectively. Accelerated aging is quantified as the difference between BA and chronological age. The statistical analysis used a multi-model validation strategy: 1) multivariate linear regression to evaluate the association between NPAR and continuous aging acceleration indicators; 2) the restricted cubic spline (RCS) model explores the nonlinear relationship; 3) stratified subgroup analysis to test for effect heterogeneity. All models were stratified for sociodemographic characteristics (age, sex, and ethnicity), lifestyle factors (smoking, alcohol consumption, and physical activity), and clinical covariates (body mass index [BMI], hypertension, and history of diabetes). RESULTS: In an analysis of 1053 RA patients in the United States, women accounted for 56.48% and men for 43.52%; the group with the highest NPAR (T3) showed more significant aging characteristics (≥65 years old 34.75%, females 62.80%, and diabetes 27.69%) and higher biological aging acceleration rates (KDM acceleration 42.81% vs. low group 25.81%; PhenoAge acceleration 62.13% vs. 37.74%; all < 0.001). After adjustment for multiple factors, the BA of KDM increased by 0.86 years for every 1 unit increase in NPAR (95% confidence interval [CI]: 0.39-1.32, < 0.001), and PhenoAge increased by 1.32 years (95% CI: 0.93-1.71, < 0.001). Taking the lowest NPAR group (T1) as the reference group, the highest NPAR group (T3) had an increased risk of accelerated aging of KDM by 149% (OR = 2.49, 95% CI: 1.44-4.31), and the risk of PhenoAge increased sharply by 259% (OR = 3.59, 95% CI: 2.17-5.95). Nonrestrictive spline curve analysis further revealed that there was a nonlinear positive correlation between the NPAR index and biological aging. When NPAR > 13.128, the growth rate of biological aging was significantly accelerated ( for nonlinear = 0.05), while when NPAR > 14.512, the risk of phenotypic aging accelerated sharply ( for nonlinear = 0.002). Area under the curve (AUC) of NPAR in the combined model for predicting biological senescence acceleration was 0.71-0.75. DISCUSSION: Elevated NPAR is significantly associated with accelerated biological aging in RA patients, and the mechanism may involve neutrophil migration dysfunction, oxidative damage caused by albumin deficiency, and chronic inflammatory pathways (such as NF-B activation). As a low-cost inflammatory marker, NPAR holds promise for integration into clinical aging risk assessment systems to identify high-risk RA populations requiring early intervention. The study's limitations include the inability to infer causality due to the cross-sectional design and a relatively small sample size, necessitating further validation through cohort studies in the future.
Decoy Receptors in Autoimmunity: Molecular Guardians and Pathogenic Players in Immune Dysregulation.
Farahani H, Kokhaei P, Ganji A … +2 more , Mosayebi G, Ghazavi A
Mediators Inflamm · 2026 · PMID 41532007 · Full text
Autoimmune disorders encompass a varied range of diseases in which the immune system mistakenly targets and attacks the body's own tissues. The causes of the conditions are unknown. It is presumed that various genetic, e...
Autoimmune disorders encompass a varied range of diseases in which the immune system mistakenly targets and attacks the body's own tissues. The causes of the conditions are unknown. It is presumed that various genetic, environmental, and immune factors all play a part. Nowadays, therapies concentrate mainly on anti-inflammatory agents with immunosuppressant medications. New research highlights the central role of decoy receptors (DcRs) in regulating the immune system. DcRs are molecular traps for cytokines and other signaling molecules, preventing them from binding to functional receptors and influencing inflammatory processes. Their activity is context-dependent, shifting the balance between protective and pathogenic responses, and DcR dysregulation has been implicated in the development of autoimmune diseases. Understanding DcR function is critical for the design of potential therapeutic interventions. DcR mechanisms are reviewed here with emphasis on structural and disease-specific functions. Targeting DcRs is a promising strategy to reconstitute immune homeostasis. Understanding the dual regulatory functions and context-dependent mechanisms is critical for designing new therapies that reduce autoimmune pathogenesis without compromising host defense mechanisms.
MicroRNA-223/NE Signaling Pathway Inhibits Lipopolysaccharide-Induced Acute Lung Injury by Regulating Neutrophil Extracellular Traps.
Zeng Z, Qin Y, He X … +1 more , Tan Z
Mediators Inflamm · 2026 · PMID 41532006 · Full text
BACKGROUND: Acute lung injury (ALI) is characterized by significant neutrophil infiltration in the lungs, representing a life-threatening condition with diverse etiologies. However, the mechanisms regulating neutrophil-a...
BACKGROUND: Acute lung injury (ALI) is characterized by significant neutrophil infiltration in the lungs, representing a life-threatening condition with diverse etiologies. However, the mechanisms regulating neutrophil-alveolar epithelial interactions and the pathophysiological roles of neutrophil infiltration in ALI remain incompletely understood. METHODS: A dose of 20 mg/kg lipopolysaccharide (LPS) was intratracheally instilled to induce ALI models in 10-week-old male microRNA-223 knockout mice (miR-223) and wild-type (WT) mice, with control group mice receiving an equal volume of phosphate-buffered saline (PBS). After 24 h of instillation, lung tissues and peripheral blood were collected from the mice. In vivo, quantitative PCR (qPCR) measured miR-223 and neutrophil elastase (NE) mRNA levels, while Western blot (WB), enzyme-linked immunosorbent assay (ELISA), and hematoxylin-eosin (H&E) staining assessed neutrophil extracellular traps (NETs) markers (H3Cit, myeloperoxidase [MPO]), inflammatory cytokines (TNF-α, IL-1β, and IL-6), and lung injury severity. In vitro, HL-60-derived neutrophil-like cells were cocultured with alveolar epithelial cells under LPS stimulation. The roles of the miR-223/NE/NETs axis were further investigated using the NETs inhibitor GSK484 and the NE inhibitor Sivelestat. RESULTS: WB experiments showed an increase in NETs-related proteins MPO and H3Cit in the lungs of WT ALI mice, with significantly enhanced expression in miR-223 mice. The lung injury scores and mortality rates in miR-223 mice were significantly exacerbated, accompanied by increased neutrophil infiltration in the lungs. Levels of inflammatory factors (TNF-α, IL-1β, and IL-6) in the serum of miR-223 mice were significantly elevated. In vitro coculture experiments demonstrated that miR-223 deficiency in neutrophil-like cells augmented NETs formation and inflammatory responses, leading to increased damage to alveolar epithelial cells. However, in vivo inhibition of NETs with GSK484 or NE with Sivelestat in miR-223 mice significantly attenuated neutrophil infiltration, inflammation, and lung injury, and improved survival. Similarly, Sivelestat pretreatment reduced NET formation and conferred protection against ALI. Consistent with the in vivo findings, inhibition of NETs with GSK484 or NE with Sivelestat in the coculture system similarly attenuated epithelial damage and inflammatory response. CONCLUSION: This study reveals that the miR-223/NE axis critically regulates NETs formation, modulating neutrophil inflammatory infiltration and neutrophil-epithelial interactions to exacerbate ALI. These findings provide potential therapeutic targets for ALI.
Association of Systemic Inflammation Indices With Mortality in Coronary Atherosclerosis Patients With and Without Standard Modifiable Risk Factors.
Yan W, Zhang B, Zhang X … +5 more , Li X, Yu Y, Liu Y, Guo L, Lv H
Mediators Inflamm · 2026 · PMID 41523989 · Full text
BACKGROUND: Standard modifiable risk factors (SMuRFs) are important causative factors leading to coronary atherosclerosis. However, a significant number of individuals develop coronary atherosclerosis despite the absence...
BACKGROUND: Standard modifiable risk factors (SMuRFs) are important causative factors leading to coronary atherosclerosis. However, a significant number of individuals develop coronary atherosclerosis despite the absence of SMuRFs. Inflammation is another major cause of atherosclerosis, and this study aims to investigate the association of the novel inflammatory markers systemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) with mortality in patients with coronary heart disease (CHD) with and without SMuRFs. METHODS: In this study, we included 1708 CHD participants from the 1999-2018 National Health and Nutrition Examination Survey (NHANES). Patients were categorized into ≥ 1SMuRF and SMuRF-less groups by questionnaire and serologic testing. SII and SIRI were categorized into four groups according to quartiles. Multivariate weighted Cox regression was used to explore the risk factors associated with mortality in patients with or without SMuRFs. Restricted cubic spline (RCS) curve was used to assess their nonlinear correlation. RESULTS: In patients with ≥1 SMuRF, all-cause mortality (SII:hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.18-1.84, < 0.001; SIRI:HR 1.66, 95%CI 1.31-2.10, < 0.001) and cardiovascular mortality (SII:HR 1.52, 95%CI 1.07-2.17, = 0.020; SIRI:HR 1.63, 95%CI 1.11-2.38, = 0.011) were significantly higher in the SII Q4 and SIRI Q4 group compared to the SII Q1 and SIRI Q1 group, respectively. In patients with SMuRF-less, the incidence of all-cause mortality was also significantly higher in the group with higher levels of SII, SIRI (SII:HR 3.32, 95%CI 1.45-7.59, = 0.004; SIRI:HR 4.25, 95%CI 1.67-10.80, = 0.002), but no significant difference was observed in cardiovascular mortality for SII (SII:HR 2.21, 95%CI 0.54-8.97, = 0.272), while a significant association was found for SIRI (SIRI:HR 11.69, 95%CI 1.43-95.21, = 0.028). The RCS analysis showed a linear trend between high levels of SII, SIRI, and elevated all-cause mortality, and cardiovascular mortality in patients with ≥1 SMurRF. In contrast, a positive linear trend between SII, SIRI, and all-cause mortality, but no significant association with cardiovascular mortality was observed in the group with SMuRF-less. CONCLUSIONS: The findings showed that SII and SIRI were positively associated with all-cause mortality in a population with CHD irrespective of the presence or absence of SMuRFs. The present study suggests that inflammation may be an important factor in the poor prognosis of patients with no specific cardiovascular risk factors, which needs to be further argued by more prospective studies.
Identification of miRNAs Expression Characteristics and Biomarkers in Serum-Derived Exosomes of Wilson's Disease Patients.
Chen H, Wang X, Ma Y … +3 more , Pu Y, Ye H, Zhang J
Mediators Inflamm · 2026 · PMID 41523988 · Full text
BACKGROUND: Wilson's disease (WD), caused by mutations in the ATP7B gene, leads to copper accumulation and multi-organ damage. Exosomal microRNAs (miRNAs) play a crucial role in cell-to-cell communication and the pathoge...
BACKGROUND: Wilson's disease (WD), caused by mutations in the ATP7B gene, leads to copper accumulation and multi-organ damage. Exosomal microRNAs (miRNAs) play a crucial role in cell-to-cell communication and the pathogenesis of diseases, yet their study in WD remains unreported. This study aims to characterize the serum exosomal miRNA signature in WD patients and investigate its potential as a source of biomarkers and therapeutic targets. METHODS: Serum exosomes from WD patients and healthy controls were isolated for RNA sequencing to identify differentially expressed miRNAs (DE-miRNAs). An integrated bioinformatics approach was employed, encompassing Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Disease Ontology (DO) analyses to systematically decipher the functional roles, pathway involvements, and disease associations of the DE-miRNAs. Selected DE-miRNAs were validated by RT-qPCR. RESULTS: We identified 59 DE-miRNAs (23 upregulated, 34 downregulated) in WD patient serum exosomes. GO analysis revealed their significant involvement in signal transduction, metal ion binding, and metabolic pathways. KEGG analysis highlighted alterations in key signaling cascades, including Ras, PI3K-Akt, and Hippo pathways. Reactome analysis further uncovered disruptions in specific biological modules, notably ubiquitin-mediated proteolysis, GPCR signaling, and spliceosome assembly. DO enrichment demonstrated significant associations with hepatocellular carcinoma, neuropsychiatric disorders, and metabolic diseases. RT-qPCR validation confirmed the reliability of DE-miRNA expression patterns ( < 0.05). CONCLUSIONS: This study establishes the first comprehensive landscape of serum exosomal miRNAs in WD, revealing their involvement in an interconnected network of pathological processes. Our findings provide a novel conceptual framework for understanding WD pathophysiology and pinpoint promising candidates for biomarker development.
RETRACTION: Proinflammatory Cytokines IL-6 and TNF-α Increased Telomerase Activity through NF-κB/STAT1/STAT3 Activation, and Withaferin A Inhibited the Signaling in Colorectal Cancer Cells.
Inflammation MO
Mediators Inflamm · 2026 · PMID 41523987 · Full text
[This retracts the article DOI: 10.1155/2017/5958429.].
[This retracts the article DOI: 10.1155/2017/5958429.].
Correction to "Discussion on the Mechanism of Gandoufumu Decoction Attenuates Liver Damage of Wilson's Disease by Inhibiting Autophagy through the PI3K/Akt/mTOR Pathway Based on Network Pharmacology and Experimental Verification".
Mediators Inflamm · 2026 · PMID 41523986 · Full text
[This corrects the article DOI: 10.1155/2023/3236911.].
[This corrects the article DOI: 10.1155/2023/3236911.].
Sirtuin 4 Knockout Aggravates Sepsis-Induced Acute Liver Injury by Enhancing Mitochondrial Fission and Mitophagy in Hepatocytes.
Li N, Ma D, Luo S … +2 more , He A, Chang S
Mediators Inflamm · 2026 · PMID 41523985 · Full text
BACKGROUND: Sepsis leads to multiorgan damage, with the liver being the main target. Sirtuin 4 (Sirt4) plays a regulatory role in mitochondrial function and metabolism, but its mechanism in liver injury caused by sepsis...
BACKGROUND: Sepsis leads to multiorgan damage, with the liver being the main target. Sirtuin 4 (Sirt4) plays a regulatory role in mitochondrial function and metabolism, but its mechanism in liver injury caused by sepsis remains unclear. METHODS: The mouse model of liver injury caused by sepsis was established by cecal ligation and puncture (CLP) surgery. The degree of liver injury in wild-type (WT) and Sirt4 gene total knockout (Sirt4-KO) mice was compared by serum AST, alanine aminotransferase (ALT), and histological analysis. The expression of mitophagy and mitochondrial dynamic indicators was detected by biochemical experiments. RESULTS: Liver injury in Sirt4-KO mice was more severe than that in WT mice after CLP, manifested as significant upregulation of mitophagy and mitochondrial dynamics imbalance. Mechanistically, Sirt4 deficiency increases mitochondrial fission and mitophagy, thereby leading to cellular damage. CONCLUSIONS: Sirt4 knockout (KO) aggravates liver injury in sepsis through increasing mitochondrial fission and mitophagy, which indicates a promising direction for future clinical treatment.
ALAS2 Prevents Neonatal Necrotizing Enterocolitis by Improving Ferroptosis in Intestinal Epithelial Cells Through Inhibition of Oxidative Stress.
Hao Z, Han J, Yao T … +6 more , Zhao Z, Fan W, Jiang Z, Wang Y, Yang X, Xu Z
Mediators Inflamm · 2026 · PMID 41509986 · Full text
Neonatal necrotizing enterocolitis (NEC) is an intestinal disease that occurs in the neonatal period. The purpose of this study was to investigate the role of 5'-aminolevulinate synthase 2 (ALAS2) in NEC-induced intestin...
Neonatal necrotizing enterocolitis (NEC) is an intestinal disease that occurs in the neonatal period. The purpose of this study was to investigate the role of 5'-aminolevulinate synthase 2 (ALAS2) in NEC-induced intestinal injury. In a neonatal mouse, NEC model was induced by high-osmolarity formula and hypoxia-cold stress, and ALAS2 expression was significantly downregulated in ileal tissues ( < 0.01), coinciding with elevated oxidative stress (increased Fe/malondialdehyde [MDA] and decreased superoxide dismutase [SOD]), inflammation (increased TNF-α/interferon-gamma [IFN-γ]), and ferroptosis activation (increased acyl-CoA synthetase long-chain family member 4 [ACSL4] and decreased ferritin heavy chain 1 [FTH1] with mitochondrial shrinkage). In vitro, tumor necrosis factor-alpha (TNF-α)/IFN-γ-treated intestinal epithelial cell (IEC) exhibited progressive ALAS2 suppression and increased necrosis. Crucially, lentivirus-mediated ALAS2 overexpression reversed these effects, reducing cell necrosis by 22% while suppressing ferroptosis markers (Fe accumulation, lipid reactive oxygen species [ROS], and mitochondrial depolarization) and oxidative damage (decreased MDA and restored glutathione [GSH]/catalase [CAT]/SOD). Untargeted metabolomics further revealed ALAS2-mediated modulation of nutrient metabolism and redox pathways. Collectively, ALAS2 ameliorates NEC by blocking oxidative stress-driven ferroptosis in IECs, proposing a novel therapeutic target.
Recombinant Thrombomodulin Domain 1 Promotes Diabetic Corneal Wound Healing by Inhibiting HMGB1 Production and NLRP3 Inflammasome.
Chen KY, Peng IC, Wu HL … +2 more , Kuo CH, Huang YH
Mediators Inflamm · 2026 · PMID 41503166 · Full text
PURPOSE: To investigate the therapeutic potential of recombinant thrombomodulin domain 1 (rTMD1) in diabetic corneal wound healing and to elucidate its underlying mechanisms using in vitro and in vivo models. METHODS: rT...
PURPOSE: To investigate the therapeutic potential of recombinant thrombomodulin domain 1 (rTMD1) in diabetic corneal wound healing and to elucidate its underlying mechanisms using in vitro and in vivo models. METHODS: rTMD1 was produced using the expression system and purified. Human corneal epithelial cells (HCECs) were cultured under normal glucose (NG) and high glucose (HG) conditions, with or without rTMD1 treatment. Wound healing rates were evaluated using a scratch assay. Diabetes was induced in C57BL/6 mice via streptozotocin (STZ) injections. Corneal wounds were created and treated with rTMD1 or PBS, and wound healing was assessed via fluorescein staining. Inflammatory markers, including HMGB1, TLR4, NLRP3, and IL-1β, were analyzed via quantitative PCR (qPCR), Western blot, and immunofluorescence staining. RESULTS: In vitro, HCECs treated with rTMD1 under HG conditions demonstrated a higher wound healing rate compared to untreated cells ( = 0.0049). In vivo, rTMD1 significantly enhanced corneal wound healing in diabetic mice, with faster wound closure compared to PBS-treated controls at 24 h ( = 0.005) and 48 h ( < 0.0001). rTMD1 treatment reduced the expression of HMGB1, TLR4, NLRP3, and IL-1β at both mRNA and protein levels, indicating suppression of inflammation. CONCLUSIONS: Topical application of rTMD1 promotes corneal epithelial wound healing in diabetic conditions by inhibiting HMGB1/TLR4/NLRP3-mediated inflammation. rTMD1 holds promise as a potential therapeutic agent for diabetic keratopathy, although further studies are needed to validate its clinical efficacy and safety.
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