Journal of Inflammation Research最新文献

{"title":"Mitochondria-Macrophage Interactions in Sepsis at Different Immune Stages: Integrating Immunometabolic Reprogramming, Organ Damage, and Therapeutic Strategies.","authors":"Jiaqi Li, Yuting Sun, Meilin He, Xueyi Liao, Qingfang Zou, Shuming Pan","doi":"10.2147/JIR.S641837","DOIUrl":"10.2147/JIR.S641837","url":null,"abstract":"<p><p>Sepsis is a life-threatening disorder caused by dysregulated host responses to infection, characterized by immune dysfunction, metabolic reprogramming, and multi-organ injury. Mitochondria, beyond their role in energy metabolism, act as central signaling hubs that integrate cellular metabolism, innate immunity, and inflammatory responses. Emerging evidence suggests that disrupted mitochondria-macrophage crosstalk forms a self-amplifying loop that drives excessive inflammation and organ dysfunction during sepsis. This review highlights recent advances in understanding how mitochondrial quality control and immunometabolic remodeling regulate macrophage activation and function. We discuss the impact of key metabolic pathways, including glycolysis, oxidative phosphorylation, tricarboxylic acid cycle remodeling, and fatty acid metabolism, on macrophage polarization, as well as the dynamic roles of mitophagy, mitochondrial biogenesis, and mitochondrial dynamics throughout sepsis progression. We further summarize current challenges and potential therapeutic strategies targeting the mitochondria-macrophage axis. Elucidating this regulatory network may provide new insights into precision medicine and the development of targeted therapies for sepsis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"641837"},"PeriodicalIF":4.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Akkermansia muciniphila</i> and Its Extracellular Vesicles Alleviate LPS-Induced Acute Respiratory Distress Syndrome in Rats: Integrated Microbiome, Metabolomic, and Transcriptomic Analyses.","authors":"Longxiong Liao, Biying Dong, Weitong Zeng, Bing Zhong, Yumei Zhang, Guiji Liu, Dongwei Zhang, Xianming Fan","doi":"10.2147/JIR.S633050","DOIUrl":"10.2147/JIR.S633050","url":null,"abstract":"<p><strong>Purpose: </strong><i>Akkermansia muciniphila</i> (AKK) and its extracellular vesicles (EVs) have immunomodulatory and metabolic effects, but their protective effects in acute respiratory distress syndrome (ARDS) remain unclear. This study compared live AKK with AKK-EVs and investigated their effects on LPS-induced ARDS using integrated microbiome, metabolome, and lung transcriptome analyses.</p><p><strong>Methods: </strong>An ARDS rat model was established by intratracheal instillation of lipopolysaccharide (LPS). Rats were randomly allocated to the control, ARDS, AKK, and EVs groups. Following model establishment, AKK or AKK-EVs were administered orally once daily for 7 consecutive days. Lung injury was evaluated by body weight, hematoxylin and eosin staining, lung wet/dry weight ratio, and bronchoalveolar lavage fluid (BALF) analysis. Fecal 16S rRNA sequencing, untargeted metabolomics, lung transcriptomics, and integrated multi-omics analyses were performed. The pulmonary expression of Il17a, Cxcl1, Tnf, and Il6 was validated by qRT-PCR.</p><p><strong>Results: </strong>Compared with the ARDS group, AKK and AKK-EVs attenuated weight loss and lung histopathological injury and reduced the lung wet/dry weight ratio, BALF total cell count and protein concentration, and BALF IL-17A and TNF-α levels. Both interventions partially remodeled the gut microbial community, including changes in Lachnospiraceae_NK4A136_group, norank_f_Muribaculaceae, Bacteroides, and Escherichia-Shigella. Metabolomic changes mainly involved lipid, amino acid, and bile acid metabolism. Lung transcriptomic analysis identified differential enrichment of the IL-17, TNF, chemokine, and cytokine-cytokine receptor interaction pathways. qRT-PCR further showed increased Il17a, Cxcl1, Tnf, and Il6 expression in the ARDS group and reduced expression following AKK or AKK-EVs intervention. Integrated analyses identified associations among alterations in gut microbiota, metabolites, and pulmonary gene expression.</p><p><strong>Conclusion: </strong>AKK and AKK-EVs alleviated LPS-induced ARDS, accompanied by remodeling of gut microbial and metabolic profiles and attenuation of pulmonary IL-17- and TNF-related inflammatory signaling. AKK-EVs may represent a potential cell-free intervention for ARDS.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"633050"},"PeriodicalIF":4.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psoriasis, Cardiovascular Risk, and Artificial Intelligence: Precision Risk Stratification Along the Skin-Vascular Axis-A Narrative Review.","authors":"Langhuan Yang, Huimei Zeng, Yan Yang, Jin Gao, Bo Wang, Yongkang Zhang, Mo Chen, Yourui Chen, Shiyu Zhang, Jikun Zheng, Xuesong Yang","doi":"10.2147/JIR.S633475","DOIUrl":"10.2147/JIR.S633475","url":null,"abstract":"<p><p>Psoriasis functions as a systemic inflammatory disorder associated with accelerated atherosclerosis via the Skin-Vascular Axis, conferring a cardiovascular (CV) risk frequently underestimated by conventional calculators. In this narrative review, we elucidate the mechanistic role of the IL-23/IL-17 pathway in vascular remodeling and highlight a critical clinical challenge: cutaneous-vascular dissociation, wherein profound skin clearance may not reflect internal vascular homeostasis. We evaluate the systemic CV impact of targeted therapies, highlighting the vasculo-protective potential and real-world observational evidence of biologics, the neutral-to-favorable cardiometabolic profile of oral PDE4 inhibitors, and the safety landscape of TYK2/JAK inhibitors. Furthermore, we assess the emerging clinical potential of Artificial Intelligence (AI) in cardio-dermatology, detailing how deep learning radiomics and novel multimodal fusion models incorporating biomarkers like GlycA can identify subclinical, vulnerable phenotypes. However, current evidence is largely derived from general cardiovascular cohorts, underscoring the need for disease-specific validation. Ultimately, we propose that AI-augmented tools should complement clinical judgment within an interdisciplinary framework to precisely stratify risk and potentially guide interventions to improve cardiovascular outcomes in psoriasis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"633475"},"PeriodicalIF":4.6,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Perioperative Buyang Huanwu-Based Traditional Chinese Medicine Intervention on Postoperative Venous Thromboembolism, Coagulation Markers and Systemic Inflammation: A Propensity Score-Weighted Retrospective Cohort Study.","authors":"Xuanfu Peng, Yao Wang, Xuelan Yang, Weijiang Xiong","doi":"10.2147/JIR.S601313","DOIUrl":"https://doi.org/10.2147/JIR.S601313","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aimed to (1) evaluate, in a propensity-score-weighted retrospective cohort, the effectiveness and safety of a standardised perioperative Buyang Huanwu-based traditional Chinese medicine (TCM) decoction combined with standard low-molecular-weight heparin (LMWH) prophylaxis on the 30-day incidence of symptomatic and asymptomatic venous thromboembolism (VTE), (2) characterise the longitudinal trajectories of coagulation (D-dimer, fibrinogen) and inflammatory (C-reactive protein [CRP]) biomarkers and (3) quantify the net clinical benefit of this integrative approach.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a retrospective cohort study of 1847 adult patients undergoing major general-surgical or gynaecological procedures between January 2020 and December 2024 at a tertiary integrative-medicine centre. Patients receiving a standardised perioperative TCM decoction based on the modified Buyang Huanwu Tang in addition to standard LMWH prophylaxis (&lt;i&gt;n&lt;/i&gt; = 892) were compared with patients receiving standard prophylaxis alone (&lt;i&gt;n&lt;/i&gt; = 955). The TCM decoction comprised seven herbal components dispensed at fixed daily doses (Huangqi, 60 g; Danggui, 9 g; Chishao, 6 g; Chuanxiong, 6 g; Honghua, 3 g; Taoren, 6 g; Dilong, 9 g) supplemented with 15 g of Danshen; granules were prepared as a single-batch good manufacturing practice-certified concentrated formulation, with the principal bioactive markers astragaloside IV, ferulic acid, paeoniflorin and salvianolic acid B quantified by high-performance liquid chromatography and required to fall within ±10% of the label content to ensure dose standardisation. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. The primary outcome was 30-day VTE confirmed by duplex ultrasonography or computed tomography pulmonary angiography, with symptomatic and asymptomatic events recorded separately. Secondary outcomes included major bleeding, length of stay, patient-reported pain and 90-day all-cause mortality. Linear mixed-effects models were used to analyse longitudinal trajectories of D-dimer, fibrinogen and CRP measured at baseline and on postoperative days 1, 3 and 7.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;After IPTW adjustment, TCM intervention was associated with significantly reduced 30-day VTE incidence (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.41-0.82, &lt;i&gt;p&lt;/i&gt; = 0.002), with consistent protection observed for both symptomatic VTE (HR: 0.55, 95% CI: 0.34-0.89) and ultrasound-detected asymptomatic distal deep-vein thrombosis (HR: 0.61, 95% CI: 0.39-0.94). Landmark analysis revealed sustained protection during both hospitalisation (HR: 0.52, 95% CI: 0.33-0.81) and the post-discharge period (HR: 0.67, 95% CI: 0.42-0.93). Linear mixed-effects modelling demonstrated significant group-by-time interactions for D-dimer (&lt;i&gt;p&lt;/i&gt; &lt; 0.001) and CRP (&lt;i&gt;p&lt;/i&gt; = 0.003), indicating accelerated biomarker clearance in the TCM group: 42","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"601313"},"PeriodicalIF":4.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of the C-Reactive Protein-Triglyceride-Glucose Index with Kidney Injury in Patients with Coronary Heart Disease: A Two-Center Cross-Sectional Study.","authors":"Mengmeng Fan, Xueping Zhang, Xianwei Tian, Keli Li, Zhiqiang Liu","doi":"10.2147/JIR.S644335","DOIUrl":"https://doi.org/10.2147/JIR.S644335","url":null,"abstract":"<p><strong>Background: </strong>The composite index of inflammation and insulin resistance (IR), the C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), has been suggested to be closely associated with cardiovascular disease. However, the relationship between the CTI and kidney injury (KI), including its subtypes [declined kidney function (DKF) and proteinuria], remains unclear in patients with coronary heart disease (CHD), and whether sex differences exist is unknown.</p><p><strong>Methods: </strong>This two-center cross-sectional study enrolled 3793 patients with CHD between September 2021 and May 2026. Multivariable stepwise-adjusted logistic regression assessed associations of the CTI with KI and its subtypes. Restricted cubic spline (RCS) analysis identified dose-response relationships and threshold effects, followed by piecewise comparisons. Subgroup analyses stratified by sex were performed to evaluate consistency across sexes. The area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and the Boruta algorithm compared the discriminative performance of the CTI versus CRP and TyG alone for KI and its subtypes.</p><p><strong>Results: </strong>Multivariable logistic regression showed that the CTI was significantly associated with KI and its subtypes in CHD patients. The overall prevalence of KI was 814/3,793 (21.5%). RCS revealed that CTI exceeding 4.8, 4.7, and 4.55, respectively, significantly increased risks of KI, DKF, and proteinuria. Notably, the increased risk of KI was particularly evident when CTI exceeded 4.45 in females and 4.96 in males. AUC, DCA, and Boruta rankings all confirmed stronger discriminative performance of the CTI than CRP or TyG alone for KI and its subtypes.</p><p><strong>Conclusion: </strong>Elevated CTI was independently associated with KI and its subtypes in CHD patients, with clear threshold effects that differed by sex and superior discriminative performance to single indicators. These associations were more pronounced in overweight/obese patients. Although CTI may help identify individuals at higher risk, the sex-specific thresholds should be regarded as exploratory threshold estimates and require external validation before clinical application.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"644335"},"PeriodicalIF":4.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish Models of Arthritis and Their Applications in Traditional Chinese Medicine Screening: Advances and Perspectives.","authors":"Jialu Luo, Min Gao, Xianglu Li, Xiang Guo, Huilian Huang, Xiaoqiang Hou, Zhigang Mei, Zhitao Feng","doi":"10.2147/JIR.S629102","DOIUrl":"https://doi.org/10.2147/JIR.S629102","url":null,"abstract":"<p><p>The zebrafish is a widely utilized model organism in medical research because of its high reproductive capacity, rapid development, transparent embryos, genetic tractability, and similarity to humans in skeletal development. In this review, we searched CNKI and PubMed up to July 30, 2026 using combinations of \"zebrafish\", \"arthritis\", \"osteoarthritis\", \"rheumatoid arthritis\", \"gouty arthritis\", \"infectious arthritis\", \"traditional Chinese medicine\", and \"natural products\". Both Chinese and English articles were considered. A total of 67 articles were initially retrieved. After manual screening against the inclusion criteria, the most relevant studies were selected for this review. Studies were reviewed when they described zebrafish arthritis-related models, inflammatory or skeletal phenotypes, or TCM/natural product screening. Current research has applied zebrafish models mainly to osteoarthritis (OA) and rheumatoid arthritis (RA), while infectious and gouty arthritis models remain less developed. These models help elucidate pathogenic genes associated with OA, evaluate induced OA-like pathology, explore immune and vascular mechanisms in RA, simulate acute gout-related innate inflammation, and investigate host-pathogen responses relevant to infectious arthritis. Compared with previous reviews, this review specifically addresses the application of zebrafish arthritis models in traditional Chinese medicine (TCM) screening, with emphasis on model classification and current limitations. TCM compounds and formulas can be evaluated in zebrafish through whole-organism phenotypes including inflammatory-cell recruitment, angiogenesis, toxicity, and drug-response patterns. These findings demonstrate anti-angiogenic activities that may be relevant to arthritis, but they do not establish therapeutic efficacy against arthritis itself. Future studies should further refine zebrafish models for specific arthritis types, report strain background and dose more consistently, and validate larval screening results in adult zebrafish or mammalian models when possible, as zebrafish are complementary screening models that cannot fully reproduce all aspects of adult human arthritis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"629102"},"PeriodicalIF":4.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleotide Metabolic Reprogramming in Sepsis: From Immune-Cell Fate to Organ Injury and Precision Therapeutics.","authors":"Chun Wang, Fu Shuying, Jin Jing, Fang Fuquan, Jie Huang","doi":"10.2147/JIR.S654590","DOIUrl":"https://doi.org/10.2147/JIR.S654590","url":null,"abstract":"<p><p>Sepsis is a life-threatening syndrome characterized by concurrent inflammation, immunosuppression, endothelial dysfunction and metabolic failure. Although current immunometabolic research primarily focuses on glycolysis, mitochondrial respiration and lipid metabolism, nucleotide metabolism links biosynthesis, redox homeostasis, epigenetic regulation and extracellular danger signalling. This Review synthesizes evidence for altered purine and pyrimidine synthesis, ribonucleotide reduction, nucleoside salvage and purinergic signalling across immune-cell populations in sepsis. We distinguish clinical observations from mechanistic evidence in experimental sepsis and hypotheses extrapolated from cancer or immune-mediated disease. Human observational studies support involvement of the extracellular ATP-CD39/CD73-adenosine axis in sepsis, while experimental studies provide complementary mechanistic evidence. By contrast, the roles of DHODH, RRM2 and the uridine-UPP1 salvage pathway remain predominantly preclinical, particularly in ferroptosis and acute organ injury. We propose that nucleotide metabolism functions as a time-, cell- and compartment-dependent regulatory network rather than a uniformly activated pathway. Clinical translation will require longitudinal metabolite-enzyme-receptor profiling, isotope-resolved flux analysis, spatial and single-cell approaches, and biomarker-defined therapeutic windows. Such strategies may enable nucleotide-directed interventions to complement antimicrobial treatment and organ support without compromising protective immunity.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"654590"},"PeriodicalIF":4.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrical Impedance Tomography-Informed Regional Functional Phenotypes in Sepsis-Associated Acute Respiratory Distress Syndrome.","authors":"Hangbo Hu, Jin Qian, Hongsheng Deng, Kun Chen, Xinyong Liu","doi":"10.2147/JIR.S644978","DOIUrl":"https://doi.org/10.2147/JIR.S644978","url":null,"abstract":"<p><p>Sepsis-associated acute respiratory distress syndrome (SA-ARDS) is a heterogeneous syndrome in which systemic inflammation, vascular dysfunction, altered fluid balance, chest-wall loading, and respiratory effort may produce regional abnormalities not captured by global respiratory variables. Electrical impedance tomography (EIT) provides continuous bedside assessment of regional ventilation and, increasingly, regional perfusion. This review summarizes EIT-derived measures relevant to SA-ARDS and examines how key sepsis-associated mechanisms may influence regional ventilation, perfusion, and mechanics. Six candidate functional patterns are proposed: collapse-shunt dominance, overdistension-dead-space dominance, perfusion-defect dominance, diffuse low aeration with limited recruitability, abdominal pressure-diaphragm interaction, and effort-related regional asynchrony. These patterns are neither mutually exclusive nor specific to SA-ARDS and may evolve over time.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"644978"},"PeriodicalIF":4.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Between Fire and Restraint: Context-Dependent Roles of Interleukins 27, 33, 35 and 37 in Acute Pancreatitis.","authors":"Serge Chooklin, Serhii Chuklin","doi":"10.2147/JIR.S643664","DOIUrl":"https://doi.org/10.2147/JIR.S643664","url":null,"abstract":"<p><strong>Background: </strong>Interleukins 27 (IL-27), 33 (IL-33), 35 (IL-35) and 37 (IL-37) occupy potentially important but biologically non-equivalent positions at the interface between inflammatory amplification, tissue protection and immune restraint in acute pancreatitis (AP). This narrative review critically synthesizes AP-specific evidence, distinguishing mechanistic participation from biomarker association and defining translational priorities.</p><p><strong>Methods: </strong>PubMed/MEDLINE, Scopus and Google Scholar were searched through July 2026. The review was structured with reference to the Scale for the Assessment of Narrative Review Articles (SANRA). Of 215 records identified, 43 underwent full-text assessment and 35 were included in the narrative synthesis (32 original studies and 3 reviews). Primary AP studies were prioritized, with landmark mechanistic studies used to interpret cytokine biology.</p><p><strong>Results: </strong>IL-33/ST2 was the most extensively studied axis and showed phase-, compartment- and molecular-form-dependent effects. Soluble ST2 correlated with severity but has not been validated for incremental prediction. IL-37 had the strongest direct protective evidence, inhibiting NLRP3-caspase-1-gasdermin D-mediated acinar-cell pyroptosis experimentally and showing an inverse association with pancreatic necrosis in patients; however, this clinical association derived from a single cohort and requires external validation. IL-35 findings were contradictory, with both severity-associated increases and reduced concentrations reported; assay characteristics may limit reliable distinction of intact bioactive IL-35 from free subunits or related complexes. Evidence for IL-27 was sparse and largely indirect. Across all four cytokines, clinical evidence remains limited by small or heterogeneous cohorts, inconsistent timing and analytical methods, and insufficient independent validation.</p><p><strong>Conclusion: </strong>These cytokines should not be considered a uniform anti-inflammatory group. IL-33/ST2 is context-dependent, IL-37 is a promising but preclinical cytoprotective candidate, and IL-35 and IL-27 remain hypothesis-generating. None is validated as a stand-alone biomarker or therapeutic target for routine AP care. Further progress requires standardized assays, longitudinal sampling and independent clinical validation.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"643664"},"PeriodicalIF":4.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KLF4 Protects Against Sepsis-Induced Coagulopathy via Inhibition of the AKT/mTOR/STAT3 Signaling Pathway.","authors":"Rongrong Zhang, Yun Hong, Darong Hai, Hongyan Du, Liwen Zhao, Zhengyan Li, Fangkai Yin, Wanli Zheng, Kaicheng Wang, Jingye Pan, Yueyue Huang","doi":"10.2147/JIR.S642803","DOIUrl":"https://doi.org/10.2147/JIR.S642803","url":null,"abstract":"<p><strong>Purpose: </strong>Coagulation dysfunction is an independent predictor of morbidity and mortality in patients with severe sepsis, yet current therapeutic options remain inadequate. This study systematically evaluated the therapeutic potential of Krüppel-like factor 4 (KLF4) in sepsis-induced coagulopathy and explored the underlying molecular mechanisms.</p><p><strong>Methods: </strong>In vivo, mice were randomized into sham operation group, cecal ligation and puncture (CLP) group, and CLP + APTO-253 groups. The KLF4 agonist APTO-253 was intraperitoneally administered to CLP-induced septic mice to evaluate systemic inflammation, coagulation dysfunction, acute lung injury, and survival outcomes. In vitro, RAW264.7 macrophages were assigned to six core treatment groups: control group, APTO-253 group, LPS group, LPS + APTO-253 group, LPS + KLF4 overexpression group, and LPS + KLF4 knockdown group. Cellular inflammatory responses, coagulation-related biomarkers, and AKT/mTOR/STAT3 pathway activity were detected.</p><p><strong>Results: </strong>In vivo, APTO-253 treatment significantly attenuated systemic inflammation and coagulopathy in septic mice via the upregulation of KLF4, accompanied by reduced levels of proinflammatory cytokines (interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α)) and coagulation-related biomarkers (fibrinogen, thrombin-antithrombin complex (TAT), D-dimer, tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1)). This therapeutic intervention ameliorated pathological manifestations, including pulmonary tissue damage, macrophage infiltration, and fibrin deposition, ultimately enhancing survival. In vitro, both APTO-253 treatment and KLF4 overexpression suppressed LPS-induced IL-6, IL-1β, TNF-α, TF, and PAI-1 through the inhibition of the AKT/mTOR/STAT3 signaling pathway. Conversely, KLF4 knockdown potentiated LPS-induced hyperactivation of this pathway, resulting in amplified proinflammatory and procoagulant responses.</p><p><strong>Conclusion: </strong>KLF4 overexpression ameliorates sepsis-induced coagulation dysfunction by inhibiting AKT/mTOR/STAT3 signaling. Thus, KLF4 represents a potential therapeutic target for coagulopathy in sepsis.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"19 ","pages":"642803"},"PeriodicalIF":4.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}