Journal of Inflammation Research最新文献

Purpose: To explore the mechanism of cuprotosis in psoriasis, screen cuprotosis related genes (PDCRGs) in psoriasis, and provide new targets for precise diagnosis and treatment of psoriasis.

Material and methods: Integrate bioinformatics analysis and experimental validation. Firstly, based on the GEO database (GSE161683, GSE166388, GSE277173), differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) in psoriasis were screened; Identification of differential cuprotosis related genes (PDCRGs) in psoriasis using a self built cuprotosis gene database (1098 CRGs); Screen key PDCRGs through PPI network, machine learning, and ROC analysis. Subsequently, a mouse model of psoriasis induced by imiquimod (IMQ) was constructed, and gene expression, copper ion levels, inflammatory factors, and oxidative stress factors were validated using qPCR, Western blot, immunohistochemistry, fluorescence, and ELISA.

Results: Thirty-four PDCRGs were identified, among which STAT1, DLD, GBP1, CXCL10, PDHB, and LIAS are Hub genes. Machine learning and ROC analysis further identified APOL6, CD274, and LIAS as key diagnostic biomarkers. PDCRGs are significantly enriched in the TCA cycle, copper ion transport, and glucose metabolism pathways. The levels of FDX1 and serum copper ions were increased in the skin lesions of psoriasis mice, accompanied by upregulation of TCA cycle key proteins and PDCRGs expression; Copper overload triggers oxidative stress and inflammation cascade.

Conclusion: APOL6, CD274, and LIAS were screened as cuprotosis markers in psoriasis. Overexpression of these PDCRGs in psoriasis model mice can promote copper ion accumulation and interfere with the TCA cycle, increase oxidative stress and inflammation levels, and ultimately lead to the occurrence of psoriasis. Therefore, targeted intervention of cuprotosis is of great significance for the clinical treatment of psoriasis.

Background: Acute pancreatitis (AP) is a common abdominal emergency, often associated with severe complications such as infected pancreatic necrosis (IPN) and the need for surgical intervention. Platelet count dynamics during the course of AP may be linked to disease progression and outcomes.

Purpose: This study aimed to identify clinically meaningful longitudinal platelet count patterns in AP.

Methods: Longitudinal platelet count patterns were derived using group-based trajectory modeling (GBTM). Generalized additive models were used to demonstrate the association between platelet counts and outcomes.

Results: 2225 AP patients are enrolled in the analysis and classified into 5 subclasses using GBTM. Class 1 (n=269) had a low initial platelet count, which increased slowly; Class 2 (n=983) and Class 4 (n=597) had different initial platelet count levels, but fluctuated within the normal range; Class 3 (n=225) and Class 5 (n=151) had different initial platelet count levels, but both increased beyond the normal range. A significantly decreased risk of infected pancreatic necrosis (IPN) is observed in classes 2 (OR 0.3, CI 0.16-0.55) and 4 (OR 0.14, CI 0.06-0.33), but the risk was comparable among classes 1 (ref), 3 (OR 1.25, CI 0.66-2.41), and 5 (OR 0.69, CI 0.28-1.56). The risks of the surgical interventions were similar. However, the 30-day and 90-day mortality rates were significantly lower in classes 2, 3, 4, and 5 than in class 1. Generalized additive models also demonstrated the lowest risk of IPN, surgical intervention, and in-hospital mortality as platelet counts remained within the normal range.

Conclusion: Patients with platelet counts within the normal range had the lowest risk of IPN, surgical intervention, and mortality. Both thrombocytopenia and thrombocytosis indicate an increased risk of IPN and surgical intervention; however, mortality is significantly increased only in patients with thrombocytopenia.

Purpose: Dihydromyricetin (DMY) is known for its wide range of pharmacological effects and has been approved as a dietary supplement. This study aimed to investigate the therapeutic effects of DMY on dextran sulfate sodium (DSS)-induced disruption of intestinal homeostasis in mice and to explore the underlying molecular mechanisms.

Methods: To establish a model of colitis, mice were treated with a 3% DSS solution, followed by gavage administration of DMY for therapeutic intervention. Techniques such as histomorphology, RT-qPCR, 16S rRNA sequencing, and Western blot analysis were used.

Results: DMY alleviated several physiological symptoms in colitis mice, including a reduction in the disease activity index (DAI) and spleen index, as well as decreases in the numbers of white blood cells, lymphocytes, and monocytes. Additionally, DMY helped repair the intestinal mucosal barrier function, reshaped the composition of gut microbiota, and regulated intestinal immune responses. These effects collectively contributed to the partial restoration of intestinal homeostasis in colitis mice. Furthermore, experiments with NLRP3^-/- mice and pseudo-germ-free mice confirmed that DMY exerts its anti-colitis effects through the gut microbiota-NLRP3 inflammasome axis.

Conclusion: DMY helps regulate intestinal homeostasis in colitis mice by suppressing the NLRP3 inflammasome via the gut microbiota. Our study provides new evidence supporting DMY as a potential therapeutic agent for colitis.

Background: Acute pancreatitis (AP) is a common gastrointestinal disease. Systemic inflammatory response syndrome (SIRS), a severe complication of AP, increases the risk of organ failure and progression to severe AP (SAP). Gut microbiota dysbiosis is linked to AP pathogenesis. The aim of this study is to investigate the gut microbiota characteristics of AP patients and their association with SIRS and organ failure.

Methods: Rectal swabs from 19 healthy controls (HC) and 88 AP patients (stratified into non_SIRS, SIRS, low/med/high_sequential organ failure assessment (SOFA) groups) were analyzed using 16S rRNA gene sequencing. Microbiota diversity, composition, and function were evaluated, and random forest diagnostic models were constructed.

Results: Compared with HC, AP (SIRS/non_SIRS) patients had altered clinical indices, reduced gut microbial richness and diversity. As SOFA scores increased, the high_SOFA group exhibited further reductions in richness and diversity. Barplots analysis showed that there were differences in the mainly dominant microbiota between HC and AP (SIRS/non_SIRS) patients. Some differentially abundant genera such as Faecalibacterium, Parabacteroides, Megasphaera, and Fusicatenibacter may be closely associated with the occurrence of AP, development of SIRS, and severity of organ failure. Furthermore, functional pathways like L-isoleucine biosynthesis, lysine biosynthesis, AMPK signaling, and glycogen biosynthesis may also play significant roles in diseases. The random forest models constructed for distinguishing between HC and non_SIRS, as well as for distinguishing between HC and SIRS, showed extremely diagnostic accuracy.

Conclusion: Gut microbiota dysbiosis is correlated with the occurrence of AP, development of SIRS, and severity of organ failure. Specific microbiota taxa and functional pathways may serve as potential therapeutic targets or diagnostic biomarkers for AP, providing a microbial perspective for personalized management of this disease.

Acute myocardial infarction (AMI) remains one of the leading causes of mortality and disability worldwide, involving complex immune and inflammatory responses. Among these, macrophages play a pivotal role as key immune cells. The polarization state of macrophages determines their function in both myocardial injury and repair. In the early phase of AMI, M1 macrophages promote inflammation and facilitate the clearance of necrotic tissue by releasing pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). However, excessive or prolonged M1 polarization may contribute to myocardial fibrosis and further deterioration of cardiac function. In contrast, M2 macrophages promote tissue repair and anti-inflammatory responses in the later phase by secreting anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), thereby reducing fibrosis and facilitating myocardial remodeling. This review summarizes the dynamic changes in macrophage polarization during AMI and elaborates on their roles in myocardial injury, inflammation, and tissue repair. Furthermore, it highlights recent advances in therapeutic strategies aimed at modulating macrophage polarization to improve AMI outcomes, including mTOR inhibitors, sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and gene-editing technologies such as CRISPR/Cas9. Overall, this review underscores the importance of regulating macrophage polarization, particularly the transition from M1 to M2, as a promising therapeutic target for AMI. Modulating macrophage function may provide novel insights into enhancing myocardial repair and preventing adverse cardiac events.

Background: Corynebacterium striatum (CS) is an uncommon but potentially fatal pathogen of infective endocarditis (IE). The literature on the patterns and clinical progression of Corynebacterium striatum infective endocarditis (CSIE) is limited. This article aims to provide insights into the clinical presentation and management of CSIE through a retrospective analysis of documented cases.

Methods: An electronic search was conducted across various databases including PubMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, and Wanfang database to identify relevant articles in both English and Chinese literature documenting CSIE. Subsequently, patient-level data were extracted and subjected to analysis.

Results: The systematic search yielded 38 patients from 35 articles. The median age was 68 [IQR 54, 73] years, and 63.2% of patients were men. A history of heart disease was present in 55.3% of cases, while 15.8% had a history of cardiovascular electronic device implantation. The mitral valve was the most commonly affected site, accounting for 52.8%. The misdiagnosis or missed diagnosis rate of CSIE was 28.9%. Microbiological confirmation by 16S ribosomal ribonucleic acid (16S rRNA) or metagenomic next-generation sequencing (mNGS) was present in 13.2% of cases. Vancomycin was the most effective antibiotic, with 41.7% of the CS isolates showing resistance to multiple drugs. Surgical intervention was performed in 55.3% of the CSIE patients, and the overall fatality rate was 37.8%, both of which were higher than those reported in standard IE due to common pathogens such as Staphylococcus aureus (surgical intervention rate 37.8%, fatality rate 22.4%) and viridans streptococci (surgical intervention rate 29.5%, fatality rate 36.6%).

Conclusion: CSIE often presents with nonspecific symptoms, making it prone to misdiagnosis or underdiagnosis. Echocardiography and blood cultures remain the primary diagnostic tools, but advanced approaches such as 16S rRNA and mNGS improve accuracy in pathogen identification. Compared to IE caused by common microorganisms (eg, Staphylococcus aureus, viridans streptococci), CSIE is associated with higher rates of surgical intervention and mortality, underscoring the urgent need for increased clinical vigilance and prompt, targeted management.

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.