Journal of Inflammation Research最新文献

Background: Cyperus rotundus (CR) is widely used in traditional Chinese medicine to prevent and treat a variety of diseases. However, its functions and mechanism of action in osteoarthritis (OA) has not been elucidated. Here, a comprehensive strategy combining network pharmacology, molecular docking, molecular dynamics simulation and in vitro experiments was used to address this issue.

Methods: The bioactive ingredients of CR were screened in TCMSP database, and the potential targets of these ingredients were obtained through Swiss Target Prediction database. Genes in OA pathogenesis were collected through GeneCards, OMIM and DisGeNET databases. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using DAVID database. STRING database and Cytoscape 3.10 software were used to construct "component-target-pathway" network, and predict the core targets affected by CR. The binding affinity between bioactive components and the core targets was evaluated by molecular docking and molecular dynamics simulation. The therapeutic activity of kaempferol on chondrocytes in inflammatory conditions was verified by in vitro experiments.

Results: Fifteen CR bioactive ingredients were obtained, targeting 192 OA-related genes. A series of biological processes, cell components, molecular functions and pathways were predicted to be modulated by CR components. The core targets of CR in OA treatment were AKT serine/threonine kinase 1 (AKT1), interleukin 1 beta (IL1B), SRC proto-oncogene, non-receptor tyrosine kinase (SRC), BCL2 apoptosis regulator (BCL2), signal transducer and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR), hypoxia-inducible factor 1 subunit alpha (HIF1A), matrix metallopeptidase 9 (MMP9), estrogen receptor 1 (ESR1) and PPARG orthologs from vertebrates (PPARG), and the main bioactive ingredients of CR showed good binding affinity with these targets. In addition, kaempferol, one of the CR bioactive components, weakens the effects of IL-1β on the viability, apoptosis and inflammation of chondrocytes.

Conclusion: Theoretically, CR has great potential to ameliorate the symptoms and progression of OA, via multiple components, multiple targets, and multiple downstream pathways.

Background: Liver injury, such as nonalcoholic fatty liver disease, is a common symptom observed in patients with gout/hyperuricaemia. However, the exact mechanisms are still unclear. There is ongoing controversy about whether representative agents like colchicine and febuxostat, commonly used to manage gout, could also help prevent the liver injury. Liver plays a crucial role in uric acid (UA) production and lipid metabolism. Thus, the study aimed to investigate the aberrant lipid metabolism in the liver during injury and the effects of these drugs.

Methods: An advanced multi-dimensional mass spectrometry-based shotgun lipidomics technology was employed for class-targeted lipid analysis of cellular lipidomes in hepatic tissue of a gouty model induced by a combination of monosodium urate crystals and high-fat diet with or without treatment with colchicine and febuxostat. Serum UA, blood urea nitrogen, creatinine, proinflammatory cytokines, expression of AMP-activated protein kinase protein, footpad histopathology, and footpad swelling and pain threshold of these mice were assessed to evaluate the progression of gout.

Results: Lipidomics analysis clearly demonstrated that the ectopic fat accumulation as well as changes in fatty acyls composition in TAG pool, impaired mitochondrial function resulted by decreased tetra 18:2 cardiolipin, and reduced 4-hydroxyalkenal bioavailability in liver tissue could contribute to liver damage to the gouty model. Treatment with colchicine or febuxostat not only ameliorated gouty symptoms but also corrected these abnormal hepatic lipid metabolism patterns.

Conclusion: This study shed light on underlying mechanism(s) for liver injury in gout/hyperuricaemia and suggested that administration of drugs like colchicine and febuxostat could prevent liver injury.

Purpose: The early diagnosis of septic cardiomyopathy remains a challenge. The present work aims to evaluate the diagnostic and prognostic value of plasma soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels in septic cardiomyopathy when compared with traditional myocardial biomarkers.

Methods: In the 143 sepsis enrolled patients, 67 and 76 patients were classified as non-septic cardiomyopathy and septic cardiomyopathy, respectively. Their blood samples were harvested up to 14th day after hospital admission for measurements of sTREM-1 and other biomarkers, such as N-terminal pronatriuretic peptide (NT-proBNP), highly sensitive troponin (TNT-HS), myoglobin (MYO), creatine kinase isoenzyme (CK-MB), etc. All the data were collected at 8:00 a.m. The area under the receiver operating characteristic curve was obtained to assess the diagnostic accuracy of those biomarkers. The Log rank test was utilized to evaluate the prognostic value of sTREM-1 on septic cardiomyopathy.

Results: Circulating sTREM-1 showed a high specificity (88.1%) and moderate sensitivity (64.5%) to distinguish patients with septic cardiomyopathy in the 143 septic patients. The diagnostic efficiency of sTREM-1 was higher than inflammatory biomarkers and traditional myocardial markers. Logistic regression revealed that plasma sTREM-1 was an independent predictor of septic cardiomyopathy. Furthermore, in the whole septic cardiomyopathy cohorts, the sTREM-1 levels in the non-survivors were significantly higher than those of survivors during ICU stay. In addition, the left ventricular systolic dysfunction had a high odds ratio (3.968) to predict 90-day mortality in septic patients with cardiomyopathy.

Conclusion: High plasma sTREM-1 level may be a diagnostic marker in predicting ICU poor outcome of patients with septic cardiomyopathy.

Background: The incidence of papillary thyroid cancer (PTC) has been increasing annually; however, early diagnosis can improve patient outcomes. Pyroptosis is a programmed cell death modality that has received considerable attention recently. However, no studies have reported using pyroptosis-related genes in PTC diagnosis.

Methods: Analyzed 33 pyroptosis-related genes in PTC transcriptome data from the Gene Expression Omnibus database. Subsequently, used the Least Absolute Shrinkage and Selection Operator (LASSO) model to construct a PTC molecular diagnostic model. Furthermore, confirmed differences in the expression of five genes between PTC and non-tumor tissues using immunohistochemistry. Collected 338 PTC and control samples to construct a five-gene PTC diagnostic model, which was then validated using a training set and underwent correlation analysis with immune cell infiltration. Additionally, validated the biological functions of the core gene NOD1 in vitro.

Results: The five-gene PTC diagnostic model demonstrated good diagnostic value for PTC. Moreover, identified three reliable subtypes of pyroptosis and found that NOD1 is involved in tumor-suppressive microenvironment formation. Notably, patients with high NOD1 expression had lower Progression-Free Survival (PFS). Additionally, NOD1 expression was positively correlated with immune markers such as CD47, CD68, CD3, and CD8. Lastly, inhibiting NOD1 showed significant anti-PTC activity in vitro.

Conclusion: Our results suggest that pyroptosis-related genes can be used for PTC diagnosis, and NOD1 could be a promising therapeutic target.

Purpose: A major limitation of long-term peritoneal dialysis (PD) is peritoneal membrane dysfunction characterized by faster peritoneal solute-transport rate (PSTR). This study aimed to identify efficient complement factors in peritoneal effluents of continuous ambulatory peritoneal dialysis (CAPD) patients that can predict the PSTR.

Methods: A multiplex suspension protein array was used to screened related complement pathways in overnight peritoneal effluents among 58 CAPD patients. Then the related complement factors in lectin and classical pathways in effluents were analyzed using ELISA kits among another cohort of 129 CAPD patients. Logistic regression modeling was fitted to predict the PSTR of PD patients.

Results: The multiplex suspension protein array showed complement factors including C2, C4b, C5, C5a, Factor D, Factor I, and MBL were detected in effluents of CAPD patients, and the effluent C2 Appearance rate (Ar) and C4b Ar levels were significantly correlated with D/P Cr and D/D0 glucose. The levels of effluents MASP-1 Ar, M-Ficolin Ar, C2 Ar and C4b Ar, which belong to the lectin pathway were also positively correlated with D/P Cr according the ELISA results and these parameters were expressed higher in the high and high-average (H/HA) groups according to the PET results. Moreover, effluent Masp-1 was independently associated with increased PSTR and adverse events related peritoneal transport function failure.

Conclusion: This study suggested that the lectin pathway may be involved in local complement activation and peritoneal injury of PD patients, intraperitoneal level of Masp-1 was an independent predictor of increased PSTR in PD patients.

Introduction: Given the limitations and adverse effects of current rheumatoid arthritis (RA) treatments, there is an urgent need for safer and more effective therapeutic options. Levamisole (LVM) is a non-specific immunomodulator with potential for treating skin diseases, tumors, and autoimmune disorders. Recognizing LVM's potential despite its controversial reputation, this study aimed to investigate its safety profile and therapeutic efficacy towards RA.

Methods: To evaluate the potential toxicity of LVM, a 28-day oral administration was conducted in SD rats, assessing general toxicity and neurotoxicity using serum biochemical indicators, the Morris water maze test, transmission electron microscopy, and H&E staining. Subsequently, the therapeutic effects of LVM on RA were evaluated.

Results: The results showed that 30 mg/kg LVM has promising therapeutic effects in the treatment of RA with negligible toxicity from 45 mg/kg to 180 mg/kg.

Discussions: This study provides valuable preclinical data on the safety and efficacy of LVM, laying the groundwork for future clinical applications and potentially offering a safer and more effective treatment option for RA patients.

Purpose: This study aimed to investigate gene expression profiles, identify potential hub genes, and predict drugs for patients with erosive esophagitis (EE). Despite its clinical significance, molecular-level exploration of this condition has been limited.

Patients and methods: RNA sequencing was performed on clinical biopsy samples from eight EE patients and eight healthy controls. Integrated bioinformatic tools were then utilized to analyze the data, including functional enrichment analysis, protein-protein interaction network analysis, weighted gene co-expression network analysis, immune infiltration analysis, and identification of small-molecule compounds. Additionally, the expressions of the identified hub genes were assessed in clinical samples.

Results: A total of 2801 genes with differential expression were identified, including four potential hub genes: SOX9, SPP1, TIMP1, and TLR4. Moreover, the overexpression of these hub genes was verified in clinical samples. Analysis of Immune infiltration indicated an imbalance in the distribution of immune cell types in patients with EE. Correlation analysis between immune cells and hub genes unveiled noteworthy relationships. Specifically, SOX9 exhibited a negative correlation with CD8 T cells but a positive correlation with resting memory CD4 T cells. SPP1 displayed a positive correlation with naïve B cells, while TIMP1 exhibited a negative correlation with resting dendritic cells. Furthermore, the study identified ten small-molecule drugs with potential therapeutic effects for EE, including loreclezole and mercaptopurine.

Conclusion: This study provides valuable insights into the molecular understanding of EE, offering new perspectives on disease mechanisms. The findings may inspire further research leading to the development of novel treatment strategies for EE.

Objective: Identifying high-risk children with poor prognoses during the early stages of sepsis and providing timely and appropriate interventions are imperative. The objective of this study was to develop a prognostic prediction model for pediatric sepsis utilizing the neutrophil to lymphocyte and platelet ratio (NLPR).

Methods: A multivariable logistic regression analysis was conducted to investigate the association between the NLPR and in-hospital mortality among septic children upon admission. To minimize the potential confounding factors that could introduce bias, a propensity score matching analysis was employed. Subsequently, a nomogram prediction model was developed to assess the risk of in-hospital mortality in septic children, incorporating the NLPR as a key factor. The performance of this prediction model was then evaluated.

Results: A total of 230 septic children were enrolled in the study. Multivariate logistic regression analysis revealed that the NLPR was an independent risk factor for in-hospital mortality, with an odds ratio of 8.31 (95% CI 3.69-18.68). The finding remained consistent after propensity score matching analysis. A nomogram prediction model was developed that incorporates the NLPR, arterial blood lactate level, and Pediatric Critical Illness Score (PCIS). Among the various models, this nomogram exhibited the highest area under the curve (AUC) value of 0.831. The calibration curve demonstrated good agreement between the predicted and observed outcomes. Decision curve analysis indicated that the prediction model outperformed the PCIS. Internal validation of the model yielded an AUC value of 0.824 and a kappa value of 0.420, indicating its reliability and accuracy.

Conclusion: The NLPR serves as an independent risk factor for in-hospital mortality among septic children. The nomogram prognostic prediction model could effectively guide clinicians in accurately predicting the prognosis of septic children, thus enabling timely and effective treatment interventions.

Periodontal disease is a common disorder affecting a wide range of people and has a high prevalence globally. Periodontitis comprises a series of inflammatory conditions affecting periodontal support tissue, which could ultimately lead to tooth loss and reduce life quality and add to the financial burden of society. Matrix metalloproteinase-12 (MMP-12) is an elastase that is produced mostly by macrophages and could degrade a wide spectrum of extracellular matrix (ECM) and also contribute to several systematic pathological conditions. Recently, researchers have reported higher expression of MMP-12 in chronic periodontitis patients. However, there are few reports on the role of MMP-12 in periodontitis pathogenicity, and the interaction between MMP-12, periodontal pathogens, and periodontal tissues remains unclear. In this review, we introduce the potentially unique role of MMP-12 in the context of periodontal inflammation earlier, summarize the possible effects of MMP-12 on the pathological process of periodontitis and the interaction of host response under the challenge of various inflammatory factors, and provide possible diagnostic and therapeutic strategies targeting MMP-12 for the management of periodontitis. Future research and policies should focus on and implement effective chairside testing methods to reduce the prevalence of periodontal diseases.

Purpose: Sepsis-associated acute lung injury (SA-ALI) is a common complication in patients with sepsis, contributing to high morbidity and mortality. Excessive inflammation and oxidative stress are crucial contributors to lung injury in sepsis. This study aims to examine the protective effects of moderate hypothermia on SA-ALI and explore the underlying mechanisms.

Methods: Sepsis was induced in rats through cecal ligation and puncture followed by intervention with moderate hypothermia (32-33.9°C). Blood, bronchoalveolar lavage fluid, and lung tissues were collected 12 hours post-surgery. Inflammatory responses, oxidative injury, SA-ALI-related pathophysiological processes, and Keap1/GSK3β/Nrf2/GPX4 signaling in septic rats were observed by ELISA, lung W/D ratio, immunohistochemistry, immunofluorescence, histological staining, Western blotting, RT-qPCR, and TEM assays.

Results: Moderate hypothermia treatment alleviated lung injury in septic rats, reflected in amelioration of pathological changes in lung structure and improved pulmonary function. Further, moderate hypothermia reduced arterial blood lactate production and suppressed the expression of inflammatory factors IL-1β, IL-6, and TNF-α; downregulated ROS, MDA, and redox-active iron levels; and restored GSH and SOD content. TEM results demonstrated that moderate hypothermia could mitigate ferroptosis in PMVECs within lung tissue. The underlying mechanism may involve regulation of the Keap1/Nrf2/SLC7A11/GPX4 signaling pathway, with the insulin pathway PI3K/Akt/GSK3β also playing a partial role.

Conclusion: Collectively, we illustrated a novel potential therapeutic mechanism in which moderate hypothermia could alleviate ferroptosis induced by excessive inflammation and oxidative stress via the regulation of Keap1/GSK3β/Nrf2/GPX4 expression, hence ameliorating acute lung injury in sepsis.