Journal of Inflammation Research最新文献

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.

Objective: Pigmented villonodular synovitis (PVNS), also known as tenosynovial giant cell tumor (TGCT), is a rare, locally aggressive mesenchymal tumor. The pathogenesis of PVNS remains poorly understood, significantly limiting current therapeutic options.

Methods: In the present study, gene expression profiles of PVNS and Osteoarthritis (OA) synovium from GSE3698, GSE175626 and GSE176133 were analyzed using integrating RNA sequencing (RNA-seq) and microarray to investigate the PVNS transcriptome. Differentially expressed genes (DEGs) were identified, gene set enrichment analysis (GSEA) and KEGG pathway enrichment analysis were used to determine the gene functional enrichment. CIBERSORT algorithm was executed to evaluate the characteristics of tissue immune infiltration. Immunohistochemical staining was used to evaluate inflammatory cell infiltration and immunofluorescence staining was used to identify the synovial fibroblasts (FLSs) derived from PVNS synovium. Additionally, Western blot, flow cytometry, immunofluorescence analysis, transwell migration and invasion assays, and wound-healing assays were performed to further explore the difference of CD90+PDPN+ FLSs between OA and PVNS.

Results: According to GSEA analysis and pathway enrichment analysis, the most significant manifestations of PVNS synovium were inflammatory infiltration and bone resorption. Increased immune cells infiltration including M2 macrophages and Neutrophils were observed through CIBERSORT algorithm and validated through immunohistochemical staining. Subsequently, scRNA-seq data was analyzed to identify 16 cell subpopulations and reveal increased proportion of CD90+PDPN+ FLS in PVNS synovium. CD90+PDPN+ FLSs in PVNS can secrete inflammatory factors, degrade bone, and exhibit invasive characteristics. These cells, typically located in the sublining layer, highly expressed IL-1β, TNF-α, M-CSF and MMP9, while expressing less OPG.

Conclusion: This study elucidates the structure of the PVNS synovium compared to OA synovium and highlights the crucial role of CD90+PDPN+ FLSs in synovial invasion and bone resorption. These findings may lead to updated treatment concepts for PVNS and reveal new therapeutic targets. This study opens promising avenues for developing targeted therapeutic strategies aimed at inhibiting the invasive and osteoclastogenic functions of CD90+PDPN+ FLSs in PVNS. Future research should focus on validating these cells as potential therapeutic targets, possibly through the use of selective inhibitors, which could help mitigate synovial hyperplasia and bone destruction in affected patients.

Purpose: This study aimed to elucidate the therapeutic effects of catalpol (CAT) on heart failure with preserved ejection fraction (HFpEF) and explore its underlying mechanisms.

Methods: An HFpEF mouse model was established by combining a high-fat diet with N^ω^-nitro-L-arginine methyl ester administration, followed by CAT treatment for four weeks. Cardiac function was assessed by echocardiography, while histopathological changes were evaluated using hematoxylin-eosin and Masson's trichrome staining. Network pharmacology and transcriptomic analyses were integrated to identify the core targets and signaling pathways of CAT in HFpEF. In vitro, H9C2 were stimulated with angiotensin II (Ang II), followed by CAT treatment, with recombinant rat S100A8 used to specifically activate the TLR4/RAGE pathway. Western blotting (WB) and quantitative real-time PCR were performed to validate the predicted signaling mechanisms both in vivo and in vitro.

Results: In vivo, CAT markedly improved multiple pathological and functional abnormalities in HFpEF mice, including obesity, glucose intolerance, hypertension, diastolic dysfunction, myocardial inflammation, and fibrosis. Integrated network pharmacology and transcriptomic analyses consistently identified the RAGE signaling pathway as the key pathway of CAT. Molecular docking revealed strong binding affinities between CAT and S100A8, RAGE, NOX4, ERK1, and MMP2. WB results further demonstrated that CAT significantly downregulated the S100A8/RAGE/NOX4 axis and its downstream effector MMP2 in cardiac tissue. In vitro, CAT alleviated Ang II-induced cardiomyocyte hypertrophy, reduced the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and the heart failure marker ANP, and inhibited S100A8, RAGE, and NOX4 protein levels. Notably, recombinant S100A8 activation weakened the protective effects of CAT.

Conclusion: CAT exerts cardioprotective effects against HFpEF by suppressing myocardial inflammation and fibrosis through modulation of the S100A8/RAGE/NOX4 signaling axis and its downstream effectors.

Rheumatoid arthritis (RA) is an autoimmune arthropathy closely associated with chronic inflammation, whose pathogenesis involves macrophages, particularly M1 macrophage-induced inflammatory responses. Mitochondria, as key organelles governing macrophage metabolism and function, regulate M1/M2 macrophage polarization through multiple pathways and signaling molecules, thereby inducing immune and inflammatory responses that contribute to RA development. Therefore, this paper delves into the intricate mechanisms by which mitochondria regulate macrophage-specific polarization. These pathways encompass metabolic processes, signaling molecules, mitochondrial dynamics, mitochondrial-associated molecules, mitochondrial autophagy, ion homeostasis, and mitochondrial translocation. The study underscores the pivotal role of mitochondria in macrophage-specific polarization and highlights the potential for basic research to intervene in RA by modulating Mitochondrial metabolism, mitochondrial dynamics, mitochondrial autophagy, and mitochondrial translocation to promote M1-to-M2 macrophage conversion and suppress RA inflammatory responses. This holds significant implications for repairing RA-induced bone destruction and advancing clinical treatment.

Background: Emerging evidence highlights reactive enteric glial cells (EGCs) as pivotal players in the pathogenesis of postoperative ileus (POI). Recent studies have demonstrated that electroacupuncture (EA) Zusanli acupoint (ST 36) effectively alleviates POI. This study aims to investigate the underlying mechanisms of EA ST 36-mediated functional restoration of POI.

Methods: A standardized intestinal manipulation (IM) procedure was conducted to establish the POI murine model. Mice were then treated with EA ST 36, and gastrointestinal (GI) motility function was measured after 24 hours. Immunofluorescence, Western blot, and hematoxylin-eosin staining were used to assess intestinal inflammation, the expression of glial fibrillary acidic protein (GFAP) and type 3 muscarinic acetylcholine receptors (m3AChRs). Vagus nerve activity was evaluated through plasma enzyme-linked immunosorbent assay combined with heart rate variability.

Results: Compared to the Sham group, animals in the IM group demonstrated GI dysfunction characterized by delayed whole gut transit, prolonged colonic bead expulsion time, and reduced heart rate variability, which accompanied by decreased acetylcholine levels, elevated Chiu's scores, upregulated GFAP expression, and downregulated m3AChRs expression. EA ST 36 effectively mitigated these changes and enhanced c-Fos protein expression in the nucleus tractus solitarius. Fluorocitrate (a glial cell inhibitor) and carbachol (a cholinergic agonist) replicated the effects of EA ST 36, which was abolished by either pretreatment with J104129 (a specific m3AChR antagonist) or surgical vagotomy.

Conclusion: The results suggest that EA ST 36 exerts its effects through vagally-mediated modulation of m3AChR signaling, which involves the reduction of the reactivity of EGCs and the improvement of GI dysfunction induced by IM.