Journal of Inflammation Research最新文献

Background: Chronic pancreatitis (CP) is characterized by significant pancreatic exocrine dysfunction, with limited targeting therapeutic strategies. It has been reported that DCHD can effectively alleviate pancreatic injury in chronic pancreatitis; however, its effect and mechanism on pancreatic exocrine dysfunction remain unclear.

Objective: To investigate the therapeutic effects of Da-Chai-Hu Decoction (DCHD) on pancreatic exocrine dysfunction in CP and explore its underlying mechanisms.

Methods: Thirty male C57BL/6 mice were divided into control, CP model, and three DCHD dose groups (11, 22, 44 g/kg). CP was induced via repeated caerulein injections (50 μg/kg), followed by 3 weeks of DCHD treatment. Histopathological analysis of pancreatic tissue (via HE staining, IHC, IF), molecular assays (Western blot, RT-PCR), and RNA-seq were performed. LC-MS/MS identified chemical components in the serum of DCHD-treated mice, and network pharmacology predicted potential targets. Mouse pancreatic acinar cells (266-6) exposed to caerulein and PI3K inhibitor LY294002 were treated with DCHD serum to validate pathways.

Results: DCHD not only alleviated pancreatic fibrosis (α-SMA) and inflammation (IL-6), but also maintained the level of Amylase. RNA-seq revealed that DCHD treatment downregulated the expression of genes related to inflammation, fibrosis, apoptosis, and ERS. The bioactive compounds in DCHD serum were identified by LC-MS/MS, and further were linked to PI3K/AKT and ERS pathway through network pharmacology. In vivo validation experiment showed that the expression of PI3K/AKT pathway and ERS markers in pancreatic tissue was significantly reduced in the DCHD group compared with CP mice (P<0.05). In vitro, serum containing DCHD enhanced the mRNA level of Ptf1-α and Cpa1 which represent pancreatic exocrine function and inhibited ERS, apoptosis, and PI3K/AKT signaling activation in 266-6 cells stimulated with caerulein. Furthermore, the expression of ERS marker including GRP78 and DDIT3 in acinar cells was significantly inhibited by PI3K inhibitors (LY294002) (P<0.05). After treatment of LY294002, the effect of DCHD-containing serum alleviating ERS of acinar cells was abrogated.

Conclusion: DCHD suppress ERS by regulating the PI3K/AKT pathway in pancreatic acinar cells and further alleviates pancreatic exocrine dysfunction. This study confirms the therapeutic potential of DCHD in pancreatic exocrine dysfunction, and offers a new therapeutic option for CP with pancreatic exocrine dysfunction.

Purpose: Systemic inflammation plays a crucial role in the progression and prognosis of non-small cell lung cancer (NSCLC), yet the prognostic value of perioperative inflammatory markers remains underexplored.

Patients and methods: We retrospectively analyzed 243 patients who underwent resection (2015-2019) at The Second Xiangya Hospital. Five inflammatory indices-neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV)-were calculated from pre- and postoperative blood counts, and their changes (Δ values) were derived. Prognostic markers were identified using receiver operating characteristic (ROC) curve analysis, Cox regression, least absolute shrinkage and selection operator (LASSO), and stepwise selection. A nomogram was developed in a training cohort and internally validated using a 70/30 hold-out split from the same center.

Results: Postoperative SII and PIV, along with their perioperative changes (ΔSII and ΔPIV), showed superior prognostic performance compared to preoperative values. The final nomogram (POST_SII, POST_PIV, clinical tumor-node-metastasis stage, smoking history, preoperative albumin, age, and gender) achieved a concordance index (C-index) of 0.85 in the training cohort, with area under the curve (AUCs) of 0.86, 0.89, and 0.94 at 1-, 3-, and 5-year, and a C-index of 0.80 with AUCs of 0.74, 0.85, and 0.90 in the validation cohort. The model surpassed TNM and clinical models and showed greater net clinical benefit in decision-curve analysis.

Conclusion: Postoperative SII and PIV are strong inflammatory predictors of survival after NSCLC resection. A nomogram integrating these markers with clinical variables provides accurate, individualized risk stratification.

The interleukin-4/its receptor (IL-4/IL-4R) axis has been identified as a pivotal driver of type 2 (Th2) inflammation. Biologics targeting this axis, particularly IL-4 receptor alpha subunit (IL-4Rα) monoclonal antibodies (such as dupilumab), provide revolutionary therapeutic options for multiple Th2 inflammatory diseases by simultaneously blocking IL-4 and interleukin-13 (IL-13) signaling. This review systematically evaluates the clinical application of IL-4/IL-4R-targeted therapies across a spectrum of indications, including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, and bullous pemphigoid. A substantial body of research, including randomized controlled trials and real-world studies, has demonstrated the efficacy of this therapy in improving disease-specific scores, enhancing lung function, and reducing the risk of acute exacerbations. However, the effectiveness of this treatment exhibits heterogeneity, with some patients developing primary resistance. With respect to safety, the therapy is generally well-tolerated; however, it is associated with a series of characteristic adverse events, including injection site reactions (incidence 8%-22%), disease-specific conjunctivitis (up to 14%-19% in patients with atopic dermatitis), nasopharyngitis, and transient eosinophilia. Future advancements in dynamic biomarker monitoring, bispecific antibody development, and precision dosing strategies hold promise for further optimizing the efficacy-safety balance and expanding therapeutic applications, including in neurodegenerative diseases. The objective of this review is to provide clinicians with a thorough, evidence-based synopsis of the current clinical value and prospects of IL-4/IL-4R-targeted therapies.

This comprehensive review aims to synthesize current evidence on sepsis-related skeletal muscle atrophy, with a focus on underlying mechanisms, diagnostic approaches, and therapeutic interventions. A systematic literature search was conducted in PubMed, Web of Science, and Cochrane Library up to October 2024, including clinical, translational, and animal studies. We critically analyzed the pathophysiological mechanisms linking sepsis to muscle wasting, including inflammatory signaling, mitochondrial dysfunction, and proteolytic pathways. Epidemiological data indicate a high incidence of muscle atrophy in sepsis patients, particularly among the elderly and those with comorbidities. Diagnostic modalities such as CT, MRI, ultrasound, and emerging biomarkers including urinary titin and myokines are discussed. Treatment strategies encompassing nutritional support, pharmacotherapy (eg, GLP-1RAs, myostatin inhibitors), and rehabilitation are evaluated. Controversies regarding etiology and treatment efficacy are highlighted. Future directions include the exploration of novel biomarkers, genomics-based personalized therapy, and long-term outcome studies. This review provides a structured and critical appraisal of the current state of knowledge, aiming to inform clinical practice and future research.

Objective: To analyze the efficacy of combined lamotrigine and levetiracetam therapy in epileptic patients and its impact on hippocampal volume and inflammatory response.

Methods: A retrospective analysis was conducted on the clinical data of 120 epileptic patients admitted to our hospital from December 2022 to February 2024. All patients met the inclusion and exclusion criteria. Based on the treatment received, patients were divided into a control group (n=60, treated with lamotrigine) and an observation group (n=60, treated with lamotrigine combined with levetiracetam). Clinical efficacy, bilateral hippocampal volume, inflammatory factors, brain injury markers, and adverse reactions were compared between the two groups.

Results: ① Clinical efficacy: The observation group had higher effective rates in seizure control and EEG epileptiform discharge improvement than the control group (P<0.05). ② Hippocampal volume: No significant differences were observed in bilateral hippocampal volume changes between the two groups before and after treatment (P>0.05). ③ Inflammatory factors: TNF-α, hs-CRP, and IL-6 levels decreased in both groups after treatment, with greater reductions in the observation group (P<0.05). ④ Brain injury markers: S-100β and HMGB-1 levels decreased in both groups after treatment, with greater reductions in the observation group (P<0.05). ⑤ Adverse reactions: The incidence of adverse reactions was comparable between the two groups (P>0.05).

Conclusion: Compared with lamotrigine monotherapy, lamotrigine combined with levetiracetam further improves treatment efficacy in epileptic patients, reduces inflammatory response and brain injury, and does not increase the risk of adverse reactions.

Background: Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage damage, but its pathogenesis remains unclear.

Objective: This study aims to identify potential therapeutic targets for OA and explore associated mechanistic pathways.

Methods: OA-related data from GWAS, eQTLGen, and GEO databases were analyzed. Differential expression analysis, WGCNA, and PPI network analysis identified OA-associated genes. Machine learning algorithms determined diagnostic markers, validated by ROC curve analysis. Mendelian randomization assessed causal relationships, and single-cell sequencing explored gene dynamics in OA cartilage. In vitro and in vivo experiments validated the findings.

Results: We identified 282 differentially expressed genes (DEGs) associated with OA, with 52 hub genes, including FGF1, as a key candidate. Machine learning identified FGF1 as a diagnostic biomarker, validated by ROC curve analysis (AUCs up to 1.000 in the training set, and 0.790 and 0.761 in validation sets). Mendelian randomization suggested a potential causal relationship between FGF1 expression and OA risk (95% CI = 1.002-1.081, p = 0.041). Single-cell sequencing explored the dynamics of diagnostic marker genes in OA cartilage progression. In vitro and in vivo experiments confirmed FGF1's role in inflammation and matrix degradation via the RAS-MAPK pathway.

Conclusion: This study confirms FGF1 as a diagnostic biomarker for OA, with a key role in pathogenesis through RAS-MAPK pathway activation. MR analysis provides suggestive causal evidence. FGF1 induces a pro-inflammatory and catabolic state in chondrocytes by upregulating MMP13 and TNFα, while inhibiting Aggrecan synthesis, driving irreversible cartilage matrix destruction. These findings support targeting FGF1 as a novel therapeutic strategy for OA.

Purpose: To investigate if protein STK11 alleviates lipopolysaccharide-induced acute lung injury (ALI), hypothesizing it activates autophagy (harmful substance clearance) via AMPK's "start signal".

Methods: Researchers used a genomics-first approach: they integrated datasets GSE66890, GSE10474, and GSE32707, screened autophagy-related differentially expressed genes in ALI via bioinformatics, and confirmed STK11 as a key regulator through protein-protein interaction analysis. They treated human lung cells with 50 μg/mL lipopolysaccharide for 24 hours to establish ALI models, then overexpressed or silenced STK11 in the cells. They assessed cell function, apoptosis, inflammatory factors, autophagy activity, and AMPK activation.

Results: Researchers verified STK11 as a key regulator of autophagy in ALI. STK11 overexpression significantly improved cell function, reduced apoptosis (lower pro-apoptotic/higher anti-apoptotic proteins), decreased IL-6/IL-8/TNF-α (mRNA/protein levels), enhanced autophagy (elevated LC3B-II, reduced P62, more autophagosomes), and activated AMPK. STK11 silencing reversed these protective effects and inhibited AMPK.

Conclusion: STK11 mitigates lipopolysaccharide-induced lung cell damage by activating AMPK-mediated autophagy, emerging as a potential therapeutic target for ALI.

Background: Ocular graft-versus-host disease (oGVHD) often presents with subtle and nonspecific symptoms following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Current diagnostic methods primarily depend on subjective clinical evaluations with limited sensitivity. This study aimed to identify serum pyroptosis-related cytokines associated with oGVHD and to develop a cytokine-based diagnostic model.

Methods: In this prospective case-control study, 116 allo-HSCT recipients (61 with oGVHD and 55 without) and 47 healthy controls were enrolled. A sandwich antibody array was used to screen differentially expressed proteins in a pilot cohort (n = 4 per group), followed by pathway enrichment analysis. Ocular surface parameters and serum levels of NLRP3, TLR4, CCL2, IL-18, IL-6, and TNF-α were measured. Linear correlation, logistic regression, receiver operating characteristic (ROC) analyses, and internal bootstrap validation were performed to evaluate diagnostic performance. A cytokine-based risk score model was established.

Results: Thirty-four upregulated proteins were enriched in immune and inflammatory pathways. Patients with oGVHD exhibited severe dry eye features and significantly higher serum levels of NLRP3, TLR4, CCL2, IL-18, and IL-6 (all p < 0.001), which inversely correlated with ocular surface parameters. A logistic model combining these five cytokines achieved excellent diagnostic accuracy (AUC = 0.960). Internal 10-fold cross-validation with 1,000 bootstrap iterations yielded a consistent mean AUC of 0.953, confirming model robustness. A simplified risk score stratified patients into low-, intermediate-, and high-risk categories with strong discriminatory power (p < 0.001).

Conclusion: A serum panel of NLRP3, TLR4, CCL2, IL-18, and IL-6 demonstrates high diagnostic accuracy and stability for oGVHD. As the diagnostic cutoffs were derived from the same dataset, potential overfitting cannot be excluded, and independent validation in larger multicenter cohorts is warranted.

Background: Glioblastoma (GBM) is the most aggressive primary tumor of the adult central nervous system, not only characterized by rapid proliferation and diffuse brain infiltration but also by a pronounced pro-inflammatory microenvironment that fuels tumor progression and therapeutic resistance. Current standard-of-care, surgical resection followed by radiotherapy and chemotherapy, offers limited survival benefit, partly due to inflammation-driven invasion and immune evasion. The Hippo signaling pathway, a critical regulator of cell proliferation, apoptosis, and tissue homeostasis, has recently been implicated in inflammatory signaling, making it an attractive therapeutic target.

Purpose: In this study, we investigated the anti-inflammatory and anti-invasive properties of 1,3,6-tri-O-galloyl-α-D-glucose (αTGG), the α-anomer of βTGG from Terminalia chebula, in comparison with pharmacological Hippo pathway inhibitors IAG933, VT107, and GNE7883.

Results: To mimic the inflammatory milieu associated with GBM, U87 cells were treated with Concanavalin A (ConA), which induced phosphorylation of ERK and IκB, key mediators of MAPK and NF-κB inflammatory pathways. Both αTGG and Hippo pathway inhibitors effectively suppressed these phosphorylation events, with VT107 showing the strongest effect. ConA exposure downregulated Hippo pathway downstream effectors (AXL, CTGF, CYR61) in a TEAD-dependent manner, highlighting the interplay between Hippo signaling and inflammatory transcriptional control. Importantly, αTGG and VT107 also significantly attenuated ConA-induced activation of proMMP-2 to MMP-2 and reduced the expression of multiple pro-inflammatory mediators, including COX2, CCL22, CCR2, CCR4, CXCL10, CXCL12, CXCR1, FASLG, IFNG, IL13, and IL17A.

Conclusion: These findings underscore the dual anti-inflammatory and anti-invasive actions of αTGG, positioning it as a promising candidate for targeting inflammation-driven GBM progression through modulation of Hippo pathway activity.