Journal of Inflammation Research最新文献

Purpose: Despite advancements in multidisciplinary treatment strategies, long-term survival of esophageal squamous cell carcinoma (ESCC) patients remain suboptimal. Identifying novel prognostic biomarkers is essential for individualized treatment and surveillance approaches. The Advanced Lung Cancer Inflammation Index (ALI), an integrative biomarker reflecting nutritional, inflammatory, and immune status, has emerged as a potential predictor of prognosis. However, its association with overall survival (OS) in non-surgical ESCC patients remains poorly understood. This study aims to evaluate the prognostic value of ALI in ESCC patients undergoing radical radiotherapy and to develop a predictive nomogram to support clinical decision-making.

Patients and methods: We retrospectively analyzed pre-radiotherapy ALI values of 266 ESCC patients treated from January 2017 to October 2022. A restricted cubic spline (RCS) model explored the link between continuous ALI levels and survival risk. Univariate and multivariate Cox proportional hazards models were used to identify independent predictors of OS, and a nomogram was constructed to predict 1 - year, 3 - year, and 5 - year OS probabilities.

Results: RCS analysis stratified patients into low (≤227.5), medium (227.5-570.4), and high (>570.4) ALI risk groups. Kaplan-Meier curves showed significant differences among the three groups, with lower ALI values associated with poorer prognosis (P = 0.0057). Multivariate analysis confirmed that ALI, radiation dose, T stage, and N stage were independent predictors of OS. A forest plot precisely quantified each variable's prognostic contribution. The developed nomogram exhibited moderate to high predictive accuracy, as reflected by the area under the time-dependent ROC curves. Decision curve analysis (DCA) indicated a net clinical benefit at 1 - year, 3 - year, and 5 - year time points.

Conclusion: ALI is an independent prognostic factor for overall survival in non-surgical ESCC patients treated with radical radiotherapy. The ALI-based nomogram demonstrates good predictive performance and may serve as a useful tool for personalized risk stratification and clinical management.

Cordyceps sinensis, an important medicinal fungus in traditional Chinese medicine, has gained increasing attention for its diverse pharmacological activities, particularly its anti-inflammatory properties. Its principal bioactive components, including cordycepin, cordycepic acid, polysaccharides, and sterols, exert significant protective effects in a wide range of inflammation-related diseases, primarily covering respiratory diseases, autoimmune disorders, neuroinflammatory conditions, and metabolic and gastrointestinal syndromes. These compounds act mainly by modulating key signaling pathways, including NF-κB, MAPK, TLR4/MyD88, PI3K/Akt, JAK/STAT, and Nrf2/HO-1. This review summarizes recent progress in the identification of anti-inflammatory components of Cordyceps sinensis and their mechanisms of action, highlights current challenges in clinical translation, and outlines future research directions. Collectively, these findings emphasize the broad potential of Cordyceps sinensis as a multi-target natural product-based anti-inflammatory therapy.

Background: Immune dysregulation is central to the pathogenesis of sepsis, yet the underlying immunomodulatory mechanisms in pediatric sepsis remain insufficiently defined. This study aimed to elucidate key immune-related gene signatures and cellular features associated with pediatric sepsis.

Methods: Integrated bioinformatic analyses were applied to identify immunomodulatory-related differentially expressed genes (IRDEGs). Immune modulation was further characterized by computing immunomodulatory scores (IMSs) using single-sample gene set enrichment analysis (ssGSEA), followed by subgroup stratification and immune cell infiltration analysis.

Results: Five hub IRDEGs-MAPK14, S100A9, HP, SERPINB1, and SIGLEC5-were identified. Among these, MAPK14 exhibited a strong association with myeloid-derived suppressor cells (MDSCs), which were significantly enriched in patients with high IMSs.

Conclusion: These findings reveal novel immunomodulatory axes in pediatric sepsis, emphasizing the role of MAPK14 and MDSCs. This work provides potential biomarkers and therapeutic targets for improving the clinical management of pediatric sepsis.

Background: Kawasaki Disease (KD), a leading cause of acquired heart disease in children, presents significant diagnostic and prognostic challenges due to its complex pathogenesis and lack of specific biomarkers, leading to potential delays in treatment and increased risk of coronary artery lesions (CALs). Sestrin2 (SESN2), a stress-inducible protein with documented cytoprotective functions and established biomarker utility in cardiovascular diseases, warrants investigation in KD.

Methods: We conducted a single-center prospective study enrolling 72 KD patients and 38 healthy controls (HCs). Serum SESN2 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Participants were stratified by CAL presence and severity. We evaluated SESN2 levels in different groups, assessed its correlations with clinical parameters and inflammatory markers, and performed ROC analysis to determine its diagnostic and predictive accuracy for KD and CAL.

Results: Serum SESN2 levels were significantly elevated in KD patients compared to HCs (P=0.001), with markedly higher levels in the KD-CAL subgroup (P=0.014), escalating stepwise with lesion severity. SESN2 positively correlated with inflammatory markers and coronary artery lesions. A substantial reduction in SESN2 was observed post-IVIG therapy (P=0.012). ROC analysis revealed SESN2 as a reliable diagnostic marker for KD (AUC=0.697) and a predictive marker for CAL (AUC=0.684).

Conclusion: Serum SESN2 is a valuable biomarker for KD, capable of reflecting disease activity and predicting CAL. This dual function highlights its potential to improve risk stratification and guide clinical management in affected children.

Background: Acute kidney injury (AKI) severely impairs renal function. In early AKI, tubular cells release damage-associated molecular patterns (DAMPs) that induce neutrophil recruitment. Infiltrating neutrophils can exacerbate kidney injury through degranulation or formation of neutrophil extracellular traps (NETs), but the specific DAMPs mediating early neutrophil chemotaxis remain unclear.

Methods: We integrated single-cell and spatial transcriptomic data from early AKI kidneys to identify signaling pathways underlying crosstalk between injured tubular cells and neutrophils. A murine unilateral ischemia-reperfusion injury (uIRI) model was then established, with intraperitoneal administration of the anti-inflammatory drug mesalazine (5-aminosalicylic acid, 5-ASA) during the perioperative period, followed by assessment of renal histopathology and function. In vitro, polymorphonuclear neutrophils (PMNs) were isolated from mouse peripheral blood and co-cultured with renal tubular cells in a Transwell migration system under hypoxia/reoxygenation (H/R), with 5-ASA treatment or Spp1 knockdown to evaluate effects on PMN migration.

Results: Integrated single-cell and spatial transcriptomic analyses revealed that injured tubular cells upregulate Spp1, which interacts with Cd44 on neutrophils. In vivo and in vitro, injured tubular cells released Spp1 in a paracrine manner, enhancing Cd44⁺ neutrophil migration, impairing tubular regeneration, and aggravating AKI progression. 5-ASA attenuated this process by suppressing Spp1 expression and paracrine signaling, thereby reducing early Cd44⁺ neutrophil infiltration, promoting tubular cell proliferation, and improving renal function.

Conclusion: This study provides the first evidence that tubular cell-derived Spp1 functions as a key DAMP mediating the early recruitment of Cd44⁺ neutrophils in AKI. By inhibiting paracrine Spp1, 5-ASA limits neutrophil migration and ameliorates renal injury, supporting its therapeutic potential in AKI. Targeting Spp1 may represent a promising new strategy for AKI treatment.

Purpose: Sepsis due to SARS-CoV-2 shares features with non-COVID-19 sepsis. Ceramides-bioactive sphingolipids-exist as long-chain (LC) and very-long-chain (VLC) species with opposing signaling effects. Whether LC and VLC ceramides are altered similarly in COVID-19 vs non-COVID-19 sepsis, and the therapeutic relevance of sphingomyelinase inhibition, remains uncertain. We characterised circulating ceramides in patients with systemic inflammatory response syndrome (SIRS) or sepsis with and without SARS-CoV-2.

Patients and methods: We performed targeted lipidomics on serum/plasma in two cohorts: (i) plasma from 157 SIRS/sepsis patients with different disease etiologies, including 23 patients with SARS-CoV-2 and 23 healthy controls; (ii) serum from 96 SIRS/sepsis patients with SARS-CoV-2 and 17 patients without SIRS/sepsis and without SARS-CoV-2. We quantified individual ceramide species in the serum or plasma of patients and controls simultaneously. The ceramide species levels of patients and controls, as well as patients with and without SARS-CoV-2, were compared. In the patients we assessed associations with C-reactive protein, cholesterol, and survival.

Results: Relative to non-septic comparators, SIRS/sepsis showed higher ceramide 18:1;O2/16:0, 18:0, 20:0, and 24:1 (p < 0.001 for all), and lower ceramide 18:1;O2/23:0, 24:0 (p = 0.001 for both), and 26:0 (p < 0.001). Ceramide profiles were comparable between SARS-CoV-2 and non-SARS-CoV-2 sepsis (p > 0.05). Several ceramides correlated positively with C-reactive protein and cholesterol, yet these variables did not account for the divergent regulation of LC (increased) versus VLC (mostly decreased) species. Neither individual ceramides nor the LC/VLC ratio was associated with survival (p > 0.05).

Conclusion: Sepsis is characterised by a reproducible ceramide signature that does not differ by SARS-CoV-2 status. These data argue against non-selective acid sphingomyelinase inhibition and instead support evaluation of selective ceramide synthase targeting as a therapeutic approach in sepsis.

Background: Prostate cancer (PCa) is a leading malignancy among men worldwide, with its progression strongly influenced by aging-associated changes in immune function and chronic inflammation. Chronic inflammation acts as a critical mechanism linking aging and immune dysfunction to tumor initiation, progression, and resistance to therapy. This bibliometric analysis aims to comprehensively evaluate the research landscape on aging, immune function, and chronic inflammation in PCa, identifying key trends, contributors, and emerging strategies for addressing these challenges.

Methods: A total of 1,556 publications, spanning January 2015 to October 2025, were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric tools, including VOSviewer, CiteSpace, and Bibliometrix, were employed to analyze publication trends, co-authorship networks, institutional collaborations, and keyword co-occurrences. Special focus was placed on senescence-associated secretory phenotype (SASP) factors, inflammatory biomarkers, and immune dysfunction as aging-related drivers of PCa.

Results: Research in this domain has grown significantly over the past two decades, with the United States, China, and Italy emerging as leading contributors. Key themes include the role of SASP factors, oxidative stress, and immune evasion in aging-related PCa progression. Biomarkers such as interleukin-6 (IL-6) and tumor mutational burden (TMB) are increasingly explored for their potential to guide personalized interventions. Emerging therapeutic strategies involve SASP-targeting interventions, immunotherapies like CAR-T cells, and combination approaches to reprogram the immunosuppressive tumor microenvironment.

Conclusion: This bibliometric analysis provides a comprehensive overview of research trends at the intersection of aging, immune function, and chronic inflammation in PCa. Rather than establishing mechanistic causality, the findings highlight chronic inflammation as a central and evolving research focus within the field. The results offer a data-driven framework for understanding current research priorities and may inform future mechanistic and translational studies aimed at improving therapeutic strategies for aging-associated PCa.

The vagus nerve, often regarded as a "guardian" of physiological homeostasis, plays a pivotal role in regulating cardiovascular, neurological, and immune functions. Notably, it modulates inflammatory responses through the inflammatory reflex, a neural circuit, that involves vagal afferent sensing of peripheral inflammation and efferent regulation via the cholinergic anti-inflammatory pathway. Sepsis is a dysregulated immune disorder triggered by infection, characterized by an initial hyperinflammatory phase. In recent years, increasing attention has been directed toward harnessing vagus nerve-mediated neuromodulation to restore immune balance in sepsis. This review summarizes current insights into the mechanisms of vagus nerve-mediated inflammatory regulation, outlines two major translational strategies, and underscore the therapeutic potential of targeting vagus nerve-mediated neuroimmune pathways in sepsis.

Chronic cerebral hypoperfusion is a major contributor to vascular cognitive impairment and dementia, primarily through its disruption of white matter integrity and promotion of neuroinflammatory cascades. The bilateral common carotid artery stenosis (BCAS) model has emerged as the predominant experimental approach for studying the effects of chronic cerebral hypoperfusion, particularly in aging-relevant contexts. This review synthesizes current knowledge of inflammatory responses in the BCAS model, with an emphasis on their temporal progression and functional consequences. We begin by outlining the clinical burden of hypoperfusion, the rationale for BCAS, and the hemodynamic phases it produces. We then examine early neurovascular unit dysfunction, including coordinated responses among endothelial cells, pericytes, and astrocytes. These changes converge on blood-brain barrier compromise, followed by loss of tight junctions, activation of matrix metalloproteinases, and routes of leukocyte entry via venules and the choroid plexus. Inflammatory mediators such as IL-1β, TNF-α, and IL-6 amplify injury, while microglia transition from acute responders to chronic effectors of white matter damage. Although many reports have catalogued inflammatory changes, causal tests remain sparse. Few studies manipulate specific cytokines, border-associated macrophages, or temporally restricted cellular pathways, leaving unvalidated the checkpoints that govern the shift from adaptive responses (angiogenesis, gliosis, debris clearance) to maladaptive, self-sustaining inflammation. Clarifying the temporal dynamics of neuroinflammation in BCAS is critical for defining therapeutic windows and developing strategies that preserve compensatory mechanisms while preventing chronic pathology. Future research should prioritize cell-specific and time-resolved approaches to identify mechanistic checkpoints that can be targeted therapeutically to mitigate hypoperfusion-driven cognitive decline.

Background: The pathogenesis of allergic asthma is complex, and the role of macrophage polarization and ferritinophagy in childhood allergic asthma is still unclear. In this study, we preliminarily investigated the polarization status of splenic and lung macrophages during the acute phase of allergic asthma, and further explored the role of ferritinophagy in allergic asthma.

Methods: Detection of three monocyte subpopulations in PBMC of children with acute exacerbations of asthma and healthy children by flow cytometry. Establish an acute-phase model of allergic asthma in young mice sensitized with HDM, evaluate airway inflammation, airway resistance, and airway remodeling. We assessed the polarization status of macrophages in mouse spleen and lung tissues by flow cytometry, RT-PCR. We also detected changes in the ferritinophagy-related indexes, FTH1 and LC3B, with flow cytometry, and changes in co-localization of ferritinophagy-associated proteins in wall-isolated alveolar macrophages by laser confocal microscopy.

Results: We found an increase in the proportion of classical monocytes and a decrease in the proportion of non-classical monocytes in the PBMCs of asthmatic children. Therefore, we wanted to verify the changes in monocyte-derived macrophages in a young mouse model. We found that the proportion of splenic and lung macrophages was altered in the HDM-induced mice, which also showed an M1-polarized state. LC3B expression in macrophages increased while FTH1 expression decreased. In addition, we also found NCOA4 and LC3B in alveolar macrophages, FTH1 and LC3B, The co localization of FTH1 and LAMP1 increased, indicating that ferritinophagy was also enhanced.

Conclusion: Our research results indicate that macrophages in the acute phase model of allergic asthma in young mice exhibit M1 polarization, and an increase in ferritinophagy is associated with the pathogenesis of allergic asthma. These findings establish an associative (not causal) relationship between the two processes, providing new ideas for therapeutic strategies.