Journal of Inflammation Research最新文献

Background: Extensive research has demonstrated that gut microbiota and its metabolites-including short-chain fatty acids, trimethylamine N-oxide (TMAO), and bile acids-play a crucial role in the pathophysiology of coronary artery disease (CAD).The bidirectional interaction between the gut microbiota and the cardiovascular system significantly influences host metabolic and inflammatory homeostasis. As a result, targeted modulation of the gut microbiota emerges as a promising adjunctive therapeutic strategy for CAD, offering potential benefits with minimal side effects.

Purpose: This study aims to elucidate the therapeutic mechanisms of the clinically validated Chinese medicine formula HJ11 in mitigating coronary heart disease (CHD), with a particular focus on its regulation of the heart-gut axis and associated atherosclerotic processes.

Study design and methods: This study established an ApoE-/- mouse model of atherosclerosis and treated with HJ11 via gavage.We investigated the effects of HJ11 on the gut microenvironment in these atherosclerotic mice. Gut microbial composition and faecal metabolite profiles were analyzed using 16S rDNA sequencing and metabolomics. Additionally, an in vitro model of atherosclerosis was used to examine whether HJ11 exerts anti-inflammatory effects by modulating the TLR4/MYD88/IκB-α signaling pathway.

Results: HJ11 exerted protective effects on coronary atherosclerosis by reducing systemic serum lipid levels and inhibiting plaque formation, vascular inflammation, and collagen deposition, while also alleviating aortic injury. It suppressed endothelial inflammation and inhibited the proliferation of vascular smooth muscle cells. In the gut, HJ11 alleviated intestinal structural damage and enhanced barrier integrity. Notably, it promoted the function of Akkermansia, a beneficial bacterium known to influence TLR4 expression. Finally, in an in vitro atherosclerosis model, HJ11 decoction inhibited cell proliferation and migration by inactivating the TLR4/MYD88/IκB-α signaling pathway-an effect that was abolished by TLR4 overexpression.

Asthma and chronic obstructive pulmonary disease (COPD) are two different and distinct airway disorders. However, some patients exhibit features of both, a condition often referred to as asthma-COPD overlap (ACO). Managing ACO is difficult because it is characterized by different inflammatory types and significant structural airway changes. Additionally, there is a lack of randomized controlled trials focusing specifically on ACO. Biologic therapies, originally developed for severe asthma and now increasingly studied in COPD, provide a precision-medicine approach by targeting cytokines and epithelial alarmins that contribute to type 2 (T2) and/or non-T2 inflammation. Current biologics, including anti-IgE, anti-IL-5, anti-IL-4Rα/IL-13, and anti-TSLP agents, are effective in the treatment of T2-high asthma and biomarker-driven COPD. This supports their use in ACO, especially for treating patients with eosinophilic or T2-dominant types. New therapies targeting IL-33/ST2, IL-17/IL-23, and dual blocking of epithelial alarmins show promise for influencing mixed inflammation profiles, though clinical evidence in ACO is limited. Selective IL-13 inhibitors exemplify pathway-specific treatment, but they are mainly suitable for T2-high subgroups. Despite promising mechanisms, evidence for biologics in ACO is mainly based on studies of asthma and COPD, and no drug is currently approved for this group. Future research should include ACO-specific clinical trials with adequate statistical power and endotype-guided patient selection. These trials should evaluate individual biologics, possibly using new endpoints such as airway remodeling, as well as mucus biomarkers, and omics-based phenotyping. These efforts will help develop personalized, mechanism-focused treatment plans that move beyond trial-and-error management and improve the role of biologics in ACO treatment.

Introduction: Despite administering combination antiretroviral therapy (cART), people living with the human immunodeficiency virus (PLWH) have been identified to be at an elevated risk of cardiovascular diseases (CVDs). Notably, inflammation and endothelial activation are likely factors associated with increased CVD risk in PLWH. Thus, the present study reviews evidence reporting on the potential link between increased markers of inflammatory, endothelial activation, and CVD risk in PLWH on cART.

Methodology: Web databases incorporating Cochrane libraries, PubMed, Web of Science, Google Scholar, and ScienceDirect were searched to identify suitable clinical research reports. The validity and reliability of the quality of the included evidence were appraised utilising the Downs and Black checklist.

Results: Fifteen clinical research reports were incorporated within the present study, involving PLWH on cART (n=7117). We classified these research reports based on short-term (≤12 months) and prolonged exposure (˃ 12 months) to cART of PLWH. Overwhelming results showed that short- and long-term exposure to cART are closely associated with elevated markers of inflammation that were consistent with the existence of endothelial activation in PLWH on cART. Prominent inflammatory markers, which were elevated included interleukin-6 (IL-6), high sensitivity C-reactive protein (hsCRP) and tumor necrosis factor alpha (TNF-α). While those indicating endothelial activation included soluble intercellular and vascular adhesion molecule-1 (sICAM-1 and sVCAM-1). The quality of included research reports was relatively high, while there was very limited information on the effect of the specific type of cART.

Conclusion: The current study supports the hypothesis indicating a close association between elevated inflammatory markers and endothelial activation potentially contributing to CVDs in PLWH on cART. However, these effects may be associated with prolonged exposure to cART in conjunction to specific cART-drug regimen combinations. Nonetheless, the available evidence is still very limited, and more research is needed to confirm these findings.

Background: Coronary artery disease (CAD) is an immune-mediated disorder driven by dysregulated T cell responses. Interleukin-27 (IL-27) has immunoregulatory properties, but its role in CAD remains unclear. This study is the first to investigate the effects of IL-27 on CD4⁺LAP⁺ T cells in CAD and to explore its interaction with interleukin-2 (IL-2) in modulating immune imbalance.

Methods: CAD severity was quantified by the Gensini score. Plasma IL-27 and oxidized low-density lipoprotein (ox-LDL) were measured by ELISA. Flow cytometry assessed CD4⁺ T cell subsets, while qRT-PCR and Western blot evaluated lineage-specific transcription factors.

Results: IL-27 levels were elevated in acute coronary syndrome and correlated with ox-LDL and Gensini scores. Patients with severe CAD showed a Th1/Th17-dominant profile and reductions in Th2, CD4⁺LAP⁺, and Tregs. In vitro, IL-27 promoted Th1 differentiation via T-bet/IFN-γ upregulation and suppressed Th2, Th17, and regulatory subsets, counteracting IL-2-induced expansion of Tregs and CD4⁺LAP⁺ cells. These effects were dose dependent and favored pro-inflammatory responses.

Conclusion: IL-27 drives immune imbalance in CAD by reinforcing Th1 polarization and antagonizing IL-2-mediated regulation. Beyond mechanistic insights, these findings identify IL-27 as a potential biomarker for disease severity and a candidate therapeutic target in CAD.

Objective: Osteoarthritis (OA) is characterized by articular cartilage degeneration, osteophyte formation, subchondral bone remodeling, synovitis, and joint capsule fibrosis, yet its underlying molecular mechanisms and the functional roles of long non-coding RNAs (lncRNAs) remain poorly understood. This study aimed to investigate the role of lncRNA NONHSAT248596.1 in the pathogenesis of OA through the miR-146a-5p/CXCR4 axis.

Materials and methods: The experimental systems included human articular cartilage samples, a rabbit model of OA, and chondrocytes treated with 100 ng/mL SDF-1. DIANA software predicted lncRNAs targeting the miR-146a-5p/CXCR4 axis. Dual-luciferase reporter assay verified the molecular interactions. The expression levels of target genes and proteins (CXCR4, miR-146a-5p, NONHSAT248596.1, TNF-α, IL-1β, MMP-13, collagen II, and aggrecan) were analyzed using qRT-PCR, Western blotting, and ELISA both in vitro and in vivo. Cell viability and apoptosis were measured by CCK-8 assay and flow cytometry, respectively. Cartilage pathology in the rabbit models was assessed via safranin O and hematoxylin and eosin staining at 4, 8, and 12 weeks.

Results: LncRNA NONHSAT248596.1 was significantly upregulated in OA patients and in SDF-1-induced chondrocytes. The dual-luciferase assays confirmed that NONHSAT248596.1 interacted with miR-146a-5p, and miR-146a-5p interacted with CXCR4 in OA. Overexpression of NONHSAT248596.1 promoted chondrocyte apoptosis (p<0.0001, n=3), upregulated MMP-13 (p<0.0001, n=3), and downregulated collagen II (p<0.0001, n=3) and aggrecan (p<0.01, n=3), while exacerbating cartilage degradation (p<0.05, n=3/group/time point). Silencing NONHSAT248596.1 or overexpressing miR-146a-5p reduced chondrocyte apoptosis and extracellular matrix degradation in vitro, which also ameliorated cartilage degradation (Mankin score: 5.9±1.7 VS 2.4±0.59, p<0.0001, n=3/group/time point) in rabbit OA models.

Conclusion: LncRNA NONHSAT248596.1 promotes OA via miR-146a-5p/CXCR4 axis by inducing chondrocyte apoptosis and extracellular matrix degradation. These results identify NONHSAT248596.1 as a potential therapeutic target for OA intervention and underscore the miR-146a-5p/CXCR4 axis as a critical regulatory pathway for cartilage protection.

Solanum tuberosum L. (potato) contains various bioactive compounds with health-promoting properties. Its extracts are composed of multiple classes of phytochemicals, among which two are of particular interest, anthocyanins, a subclass of polyphenols, and steroidal glycoalkaloids. The predominant glycoalkaloids, α-solanine and α-chaconine, along with anthocyanins, exhibit potent antioxidant, anti-inflammatory, and anticancer activities. Both α-solanine and α-chaconine have demonstrated pro-apoptotic, anti-proliferative, and anti-inflammatory effects in various cancer models. These compounds have been shown to modulate inflammation-associated pathways implicated in carcinogenesis. However, their relevance to inflammation-driven oral malignancies, particularly oral squamous cell carcinoma (OSCC), remains unclear. This scoping review followed PRISMA-ScR guidelines. A systematic search of PubMed and Scopus was conducted for articles published up to December 2024 using predefined keywords. Eligible studies investigated the anticancer or anti-inflammatory effects of glycoalkaloids or anthocyanins from S. tuberosum in vitro or in vivo. Eighteen studies met the inclusion criteria: 12 in vitro, 2 in vivo, and 4 combining both. Most studies focused on colorectal (n = 6), breast (n = 4), and lung (n = 3) cancers. Treatments with glycoalkaloids (1-50 μM) or anthocyanins (10-200 μg/mL) demonstrated pro-apoptotic, anti-proliferative, and anti-angiogenic effects. However, no study evaluated these compounds in OSCC models. Glycoalkaloids and anthocyanins from S. tuberosum exhibit promising anticancer and anti-inflammatory properties in various types of cancer. The absence of OSCC-focused research highlights a significant gap and the need for future studies in this context.

Purpose: To investigate the predictive value of peripheral blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), neutrophil percentage-to-albumin-ratio (NPAR), and D-dimer in the efficacy and prognosis of immunotherapy for extensive-stage small cell lung cancer (ES-SCLC).

Patients and methods: A total of 70 ES-SCLC were included. The diagnostic performance of inflammatory indexes and D-dimer in predicting the efficacy and prognosis of immunotherapy was evaluated using receiver operating characteristic curve (ROC). Disease control rate (DCR) was used as the assessment indicator for immunotherapy efficacy, and progression free survival (PFS) > 6 months was used as the judgement indicator for better prognosis. Using Lasso regression and logistic multivariate analysis to predict the efficacy and prognosis of immunotherapy, and the optimal cut-off value was determined according to the area under the ROC curve. Kaplan-Meier survival analysis was applied to compare survival differences between groups.

Results: At baseline, PLR can predict the efficacy of immunotherapy in ES-SCLC patients, but cannot predict their prognosis. After two cycles of immunotherapy, NLR can not only predict the efficacy and prognosis of immunotherapy, but also be identified as an independent predictor of long-term PFS in multivariate analysis (P<0.01). The long-term PFS rate of the low NLR2 group (<2.2) was significantly higher than that of the high NLR2 group (≥ 2.2) (P<0.001), with median PFS of 4.83 months vs 9.9 months, respectively, P<0.001.

Conclusion: After two cycles of chemotherapy combined with immunotherapy, the efficacy and prognosis of NLR and ES-SCLC immunotherapy are closely related and can serve as effective and reliable predictive indicators.

Background: Sjögren's Syndrome (SS) is the second most prevalent autoimmune disease in China without effective therapy. Current evidence indicates safety and effectiveness of CheReCunJin formula (CRCJ) in treating SS. However, the underlying mechanism remains unclear.

Methods: UPLC-Q-TOF-MS was applied for compound identification. Multiple components, targets and pathways involved in the treatment of SS with CRCJ were predicted by network pharmacology. Molecular docking was used for preliminary validation. NOD mouse, a classic spontaneous SS model, was used to examine the therapeutic effects on SS of CRCJ. The potential mechanism of CRCJ to mitigate SS was investigated by serum untargeted metabolomics. Validation of key pathway and targets was conducted using flow cytometry, ELISA, immunohistochemistry, Masson staining, and Western blot.

Results: 373 compounds were identified in CRCJ. Through network pharmacology and molecular docking, 15 main components (eg, luteolin 7-O-β-D-glucoside, rutin, 1,4-dicaffeoylquinic acid, anemarsaponin C), 10 core targets (including HSP90AA1, TNF, MMP9, MAPK1, IL6), and the key pathway for CRCJ treating SS, IL-17 signaling pathway, were screened out. In NOD mice, CRCJ demonstrated the ability to improve salivary flow rate and water intake, reduce submandibular gland (SMG) tissue damage, and diminished the levels of IFN-α, IFN-β, IgG in serum. CRCJ modulated metabolic disorders, differentially regulating 63 metabolites and 6 metabolic pathways. Additional validation showed that CRCJ inhibited the Th17 cell activation, downregulated IL-17 signal transduction, and improved ECM degradation in SMG.

Conclusion: CRCJ protected salivary glands in SS by inhibiting IL-17 signal-mediated inflammatory cascade, an effect likely attributable to key bioactive components such as luteolin 7-O-β-D-glucoside, rutin, 1,4-dicaffeoylquinic acid, and anemarrhenasaponin C. This study provides a foundation for the further development and clinical application of CRCJ for the treatment of SS.

Purpose: Prognostic heterogeneity remains a challenge in hepatocellular carcinoma (HCC) following curative resection. Inflammatory markers such as the platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), and systemic inflammation response index (SIRI), as well as liver fibrosis markers including gamma-glutamyltransferase-to-lymphocyte ratio (GLR), gamma-glutamyltransferase-to-platelet ratio (GPR), and AST-to-ALT ratio (AAR), have shown prognostic potential. This study aimed to evaluate their predictive value for survival after resection.

Methods: We retrospectively analyzed 187 patients with HCC who underwent curative resection between 2008 and 2022. Preoperative inflammatory and fibrosis markers, along with clinical variables, were assessed using univariate and multivariate Cox regression for overall survival (OS) and disease-free survival (DFS). Kaplan-Meier analysis and nomogram models were used to estimate 1-, 3-, and 5-year survival.

Results: Multivariate analysis identified elevated SII, AAR, low PNI, tumor thrombus, and postoperative complications as independent predictors of poor OS, while only tumor thrombus and SIRI independently predicted DFS. SII, AAR, and PNI were also significantly associated with aggressive tumor characteristics. Patients with all three adverse markers (high SII, high AAR, low PNI) showed significantly poorer OS and DFS. A prognostic score incorporating these markers and nomogram models were constructed to predict OS and DFS after resection.

Conclusion: SII, AAR, and PNI are independent prognostic indicators for HCC following resection. The proposed prognostic score and nomograms may assist in individualized survival assessment and postoperative decision-making.

Purpose: CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine (TCM) used for the treatment of Candida-related infections. In this study, we adopted a comprehensive approach integrating network pharmacology and animal validation to investigate the potential targets and underlying mechanisms of the CHGX formula against systemic candidiasis.

Methods: Active ingredients and potential targets of CHGX were identified via the TCMSP, Swiss Target Prediction, and TCMID databases. Systemic Candida infection targets were retrieved from the GeneCards and OMIM databases. The protein-protein interaction (PPI) network of common targets was constructed via STRING, followed by topological analysis to identify hub nodes. Functional enrichment analyses were conducted via Metascape. Molecular docking studies were performed via AutoDock. A murine model of systemic Candida albicans infection was established to evaluate the therapeutic efficacy of CHGX formula.

Results: A total of 103 active compounds and 279 potential targets of the CHGX formula were identified, yielding 53 common targets between Candida infection-related targets and drug-related targets. Topological analysis of the PPI network identified 15 core targets, 25 significantly enriched KEGG pathways, and 38 enriched GO terms. Molecular docking studies demonstrated robust binding affinity between key CHGX compounds and the identified core targets. In vivo animal experiments revealed that CHGX significantly reduced mortality, improved body weight, mitigated renal pathology, decreased the kidney index, reduced the fungal burden, and alleviated tissue damage in systemic Candida infection. Furthermore, CHGX exerts immunomodulatory and anti-inflammatory effects by modulating macrophage and Th17/Treg cell populations, as well as by regulating cytokines levels.

Conclusion: This study elucidates the potential multi-pathway and multi-target mechanisms underlying the therapeutic efficacy of the CHGX formula against Candida infectious diseases, indicating its potential as a novel alternative antifungal drug and providing a scientific basis for its clinical application and further development.