Journal of Inflammation Research最新文献

Background: Inflammation, immunity, and nutriture are associated with prognosis in cardiovascular disease. We aimed to devise a novel nomogram model based on inflammation and nutrition indexes that accurately predicts Major adverse renal and cardiovascular events (MARCE) in patients diagnosed with acute coronary syndrome (ACS) and coexisting chronic kidney disease (CKD).

Methods: We enrolled 685 individuals with ACS and CKD between January 2013 and August 2021. All patients were randomized into the training (70%) and validation (30%) cohorts. Univariable and multivariable Cox regression analyses were used to identify independent predictors for MARCE. The performance of the nomogram model was evaluated using receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis (DCA). The performance of the nomogram and GRACE score were compared.

Results: The nomogram included six variables: age, left ventricular ejection fraction, systemic immune-inflammatory index (SII), controlling nutritional status (CONUT) score, use of beta-blockers, and use of statins. The constructed nomogram demonstrated robust predictive performance, achieving ROC ranging from 0.830 to 0.935 in the training set and 0.793 to 0.889 in the validation set, respectively. Furthermore, the calibration curves exhibited excellent agreement between the predicted probabilities and the observed outcomes, indicating the reliability of the nomogram's predictions. Finally, the DCA confirmed the clinical value of the nomogram by demonstrating its potential to improve decision-making processes in the context of managing the condition under study. Compared with the GRACE score, the nomogram was superior in terms of both discrimination and reclassification ability.

Conclusion: Our novel nomogram, which incorporates the CONUT score and SII, shows promising utility for predicting MARCE in patients with ACS and CKD. The identification of patients at heightened risk through our nomogram model is paramount as it serves as a cornerstone for the implementation of targeted interventions aimed at modifiable variables.

Background: Psoriasis is characterized by accelerated proliferation of epidermal keratinocytes. IL-27 is relevant to psoriasis pathogenesis. We previously found that IL-27 stimulates the proliferation of keratinocytes. However, the mRNAs involved in the process have not been fully studied. This study aims to identify potential pathways and hub genes associated with proliferation in keratinocytes with IL-27 intervention by bioinformatics analysis.

Methods: The mRNA expression profiles from HaCaT cells with or without IL-27 treated were analyzed by bioinformatics tools. The protein-protein interaction (PPI) network was constructed to screen gene clusters and hub genes associated with proliferation. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to identify the function of the mRNAs. The GEO database and quantitative real-time PCR (qPCR) were used to verify the expression levels of hub genes in psoriatic skin lesions and IL-27-treated psoriasiform keratinocytes, respectively.

Results: We found 1257 differentially expressed genes and screened 2 crucial gene clusters. GO analysis revealed that Cluster 1 was mainly enriched in "Mitotic sister chromatid segregation" and "Spindle". Cluster 2 was mainly enriched in the "Pyruvate metabolic process" and "Oxidoreductase complex". KEGG analysis showed that Cluster 1 and Cluster 2 were mainly enriched in "Cell cycle" and "Glycolysis/Gluconeogenesis", respectively. We then identified 6 hub genes enriched in the two pathways, including CCNB1, PTTG1, CDC20, PLK1, PKM, and LDHA. GSEA complemented the role of the mitochondrial "Oxidative phosphorylation" pathway. Moreover, we found that 6 hub genes were upregulated in psoriasis skin lesions and IL-27 elevated the hub genes expression in M5-induced psoriasiform keratinocytes.

Conclusion: IL-27 possibly promotes glycolysis, mitochondrial oxidative phosphorylation, and cell cycle progression in keratinocytes. Additionally, we identified CCNB1, PTTG1, CDC20, PLK1, PKM, and LDHA as hub genes that may be involved in the mechanism of IL-27 facilitating keratinocyte proliferation in psoriasis.

Background: The decrease expression of PGC-1α contributes to perioperative neurocognitive disorders (PND). This study aimed to investigate the effects of the PGC-1α agonist ZLN005 in preventing PND and to explore the potential mechanism.

Methods: C57BL/6 mice were randomly divided into four groups: the control group (Group C), the surgery group (Group S), the surgery and ZLN005 (5 mg/(kg⋅d)) group (Group L), and the surgery and ZLN005 (7.5 mg/(kg⋅d)) group (Group H). Except for Group C, the other three groups received intraperitoneal injections of vehicle or ZLN005 once a day from 3 days before surgery to 3 days after surgery. The open field test, novel object recognition test and fear conditioning test were performed to measure anxiety behaviors, locomotor activity and memory. The levels of IL-6 and IL-1β were measured at 24 hours after surgery. ATP and ROS levels were measured at 3 days post-surgery. PGC-1α, NRF-1, Atp5d, Atp5k and Cox5a were measured at one day or three days post-surgery.

Results: ZLN005 treatment improved the cognitive function of mice in Group L and Group H compared with Group S. The expression of IL-6 and IL-1β in the hippocampus of the S group was increased after surgery, and ZLN005 reduced the expression of IL-6 and IL-1β in the hippocampus of mice one day after surgery. There were parallel decreases in the expression of PGC-1α/NRF-1 and mitochondrial function in the hippocampus of the Group S mice compared with the Group C mice. The expression of PGC-1α/NRF-1 and mitochondrial function were upregulated after ZLN005 treatment.

Conclusion: Neuroinflammation and mitochondrial damage are involved in the occurrence of PND. ZLN005 activates PGC-1α to increase the expression of mitochondrial proteins, improve mitochondrial function, and ultimately ameliorate the cognitive status of mice after surgery.

Background: Parkinson's disease (PD) is a movement disorder that lacks proven biomarkers. Case-control genome-wide association studies revealed the potential effect of galectin‑3 (GAL3) on motor progression in PD patients. Based on this finding, our study aimed to explore the correlation between serum GAL3 levels and motor performance in PD patients.

Methods: Five hundred PD patients and 200 healthy controls were recruited. The serum levels of GAL3 were measured in participants by enzyme linked immunosorbent assay (ELISA). The baseline characteristics of the participants were collected, and the associated scale scores were obtained.

Results: Compared with healthy controls, the serum levels of GAL3 were greatly increased in PD patients. These levels could distinguish between PD patients and healthy controls with a sensitivity of 0.798 and a specificity of 0.815 (AUC = 0.795, 95% CI 0.757-0.834, P < 0.001). Patients with age >60 years tended to have higher serum GAL3 levels, disease duration, Hoehn-Yahr stage, MDS-UPDRS III total score, tremor subscores, rigid subscores, and bradykinesia subscores than those with age ≤60 years. When adjusting for confounders, higher GAL3 level was significantly correlated with MDS-UPDRS III total score and rigid subscores. In men with PD, GAL3 was significantly correlated with MDS-UPDRS III total score; but the association between GAL3 and bradykinesia subscores was found in women. Moreover, the associations between GAL3 with MDS-UPDRS III total score and bradykinesia subscores were significant in patients with age >60 years.

Conclusion: Higher GAL3 level was related to more severe motor performance in patients with age >60 years, and it may be a potential predictive biomarker for motor performance in PD patients.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive liver disorder with a rising prevalence. It begins with lipid accumulation in hepatocytes and gradually progresses to Metabolic-associated steatohepatitis (MASH), fibrosis, cirrhosis, and potentially hepatocellular carcinoma (HCC). The pathophysiology of MASLD is complex and involves multiple factors, with oxidative stress playing a crucial role. Oxidative stress drives the progression of MASLD by causing cellular damage, inflammatory responses, and fibrosis, making it a key pathogenic mechanism. The Nuclear Factor Erythroid 2-Related Factor 2 / Heme Oxygenase-1 (Nrf2/HO-1) signaling axis provides robust multi-organ protection against a spectrum of endogenous and exogenous insults, particularly oxidative stress. It plays a pivotal role in mediating antioxidant, anti-inflammatory, and anti-apoptotic responses. Many studies indicate that activating the Nrf2/HO-1 signaling pathway can significantly mitigate the progression of MASLD. This article examines the role of the Nrf2/HO-1 signaling pathway in MASLD and highlights natural compounds that protect against MASLD by targeting Nrf2/HO-1 activation. The findings indicate that the Nrf2/HO-1 signaling pathway holds great promise as a therapeutic target for MASLD.

Introduction: Methotrexate (MTX) is a widely used anti-metabolite drug in cancer therapy, but its efficacy is often hindered by reactive oxygen species (ROS)-induced cellular toxicity. Resveratrol, a natural polyphenol, possesses antioxidant and anticancer properties. Therefore, this in vitro study aimed to investigate the synergistic anti-proliferative and anti-inflammatory effects of MTX and resveratrol in human THP-1 cells.

Methods: THP-1 cells were differentiated into macrophage-like cells using phorbol 12-myristate 13-acetate. In vitro experiments assessed the impact of various concentrations of MTX and resveratrol on cell viability and proliferation using the MTT assay. Concentration-effect curves were generated to elucidate their relationship. Gene expression was analyzed by RT-qPCR, while chemokine expression was measured via ELISA. Phagocytic and migratory activities were also evaluated.

Results: Differentiated THP-1 cells were treated with MTX and resveratrol and stimulated with dimethyl sulfoxide (DMSO) and lipopolysaccharide (LPS) as inflammatory stimuli. The combination of MTX and resveratrol exhibited an anti-proliferative effect in THP-1 cells (p = 0.03). The concentration-effect curve revealed IC50 values of 49.15 µg at 24 hours (R = 0.8236) and 2.029e-005 µg at 48 hours (R = 0.97) for MTX, and 20.17 µg at 48 hours (R = 1.000) and 55.38 µg at 96 hours (R = 0.9666) for resveratrol. Co-treatment with MTX and resveratrol significantly reduced mRNA and chemokine expression of CCL2, CCL3, CCL4, CCL5, and CXCL10 (p < 0.05). Moreover, decreased phagocytic and migratory activities were confirmed by phagocytosis and migration assays (p < 0.05).

Conclusion: The combination of MTX and resveratrol effectively attenuated pro-inflammatory activity in THP-1 cells, as evidenced by the downregulation of mRNA and chemokine expression. These findings suggest that the synergistic effects of MTX and resveratrol hold promise for enhancing cancer therapeutics.

Purpose: Atopic dermatitis (AD) is a prevalent skin condition worldwide. The immune response plays a crucial role in the pathogenesis of AD. Arctiin (ARC), a natural lignan, has been extensively investigated because of its anti-inflammatory, antioxidant, and anticancer properties. However, the impact of ARC on AD remains uncertain. Therefore, this study investigated the therapeutic effects of ARC in AD.

Methods: AD-like lesions were induced in mice by applying 2,4-dinitrochlorobenzene (DNCB). The efficacy of ARC in AD was assessed by measuring skin lesion scores and thickness, pathological observation, and serum IgE concentrations. The expression of relevant proteins and genes in the back skin of the mice was assessed. Moreover, the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways were assessed in HaCaT cells stimulated with TNF-α and IFN-γ.

Results: ARC effectively alleviated AD-like dermatitis induced by DNCB in mice, reducing the skin thickness, mast cell infiltration in skin tissue, and serum total IgE levels. In addition, the expression of IL-1β and the mRNA transcription of TSLP and IFN-γ were downregulated. ARC also suppressed the TLR4/MyD88/NF-κB pathway, and molecular docking confirmed that ARC had exceptional binding properties with TLR4. Moreover, ARC ameliorated pyroptosis by inhibiting the activation of the nod-like receptor protein-3/Caspase-1/GSDMD cascade.

Conclusion: ARC has remarkable anti-AD effects by inhibiting inflammation and pyroptosis through the TLR4/MyD88/NF-κB and NLRP3/Caspase-1/GSDMD signaling pathways. This suggests that ARC has potential as a new drug candidate for treating AD, which provides a novel approach to the clinical management of AD.

Objective: This study aimed to establish a model for identifying chronic gastritis with the traditional Chinese medicine damp phlegm pattern by examining metabolite changes in the tongue coating of patients. It also explored the role of metabolic pathways in the pathogenesis of this condition.

Methods: This cross-sectional study involved 300 patients diagnosed with chronic gastritis. Of these, 200 patients exhibited the damp phlegm pattern, while 100 did not. Metabolomic methods employing GC-TOF-MS and UHPLC-QE-MS were utilized to identify various metabolites in the tongue coating of patients. An identification model for chronic gastritis with the damp phlegm pattern was created based on ROC curves derived from differential biomarkers. Additionally, 50 samples not included in model construction were collected for external validation.

Results: Comparison of the damp phlegm pattern group with the non-damp phlegm pattern group revealed a total of 116 differential metabolites. Among these, lipids and lipid-like compounds were most abundant, comprising 27 types, which included four lipid metabolites related to sphingomyelin metabolism. The ROC model, which included phenol, 2.6-diaminoheptanedioic acid, and N-hexadecanoyl pyrrolidine, demonstrated the highest accuracy, with accuracy, sensitivity, and specificity metrics of 94.0%, 91.0%, and 87.0%, respectively. Furthermore, external validation using tongue coating metabolites from 50 patients revealed accuracy, sensitivity, and specificity in the validation set of 93.9%, 90.6%, and 83.3%, respectively.

Conclusion: Differential metabolites between patients with the damp phlegm pattern and those without are primarily lipids and lipid-like compounds. N-hexadecanoyl pyrrolidine, phenol, and 2.6-diaminoheptanedioic acid may serve as potential biomarkers for chronic gastritis characterized by the damp phlegm pattern.

Introduction: Insulin, the key hormone for glucose regulation, has garnered attention for its role as an immune modulator. Impaired insulin signaling in the central nervous system is linked to neuroinflammation and neurodegenerative diseases. Microglia, the resident macrophage-like immune cells in the brain, are key regulators of neuroinflammation. However, the mechanisms by which insulin influences microglial immune responses remain relatively unknown.

Methods: This study aimed to assess the effects of post-treatment with insulin [30 minutes after lipopolysaccharide (LPS) exposure] on LPS-induced inflammatory responses in BV2 microglial cells.

Results: Post-treatment with insulin potentiated LPS-induced production of nitric oxide and pro-inflammatory cytokines, such as TNF and IL-6, through activation of the Akt/NF-κB pathway. Insulin also enhanced the ability of BV2 cells to phagocytose bacteria particles and β-amyloid fibrils. Conversely, insulin inhibited activation of NADPH oxidase and reduced intracellular levels of reactive oxygen species in LPS-treated BV2 cells.

Conclusion: Insulin enhances microglial immune competence when challenged by endotoxins but mitigates oxidative stress in these cells.

Purpose: Acute pancreatitis (AP) is a common digestive disorder characterized by high morbidity and mortality. This study aims to uncover differentially expressed long noncoding RNAs (lncRNAs) and mRNAs, as well as related pathways, in the early stage of acute pancreatitis (AP), with a focus on the role of Neat1 in AP and severe acute pancreatitis (SAP).

Methods: In this study, we performed high-throughput RNA sequencing on pancreatic tissue samples from three normal mice and three mice with cerulein-induced AP to describe and analyze the expression profiles of long non-coding RNAs (lncRNAs) and mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted on the differentially expressed mRNAs to identify enriched pathways and biological processes. An lncRNA-miRNA-mRNA interaction network was constructed to elucidate potential regulatory mechanisms. Furthermore, we utilized Neat1 knockout mice to investigate the role of Neat1 in the pathogenesis of cerulein-AP and L-arginine-severe acute pancreatitis (SAP).

Results: Our results revealed that 261 lncRNAs and 1522 mRNAs were differentially expressed in the cerulein-AP group compared to the control group. GO and KEGG analyses of the differentially expressed mRNAs indicated that the functions of the corresponding genes are enriched in cellular metabolism, intercellular structure, and positive regulation of inflammation, which are closely related to the central events in the pathogenesis of AP. A ceRNA network involving 5 lncRNAs, 226 mRNAs, and 61 miRNAs were constructed. Neat1 was identified to have the potential therapeutic effects in AP. Neat1 knockout in mice inhibited pyroptosis in both the AP/SAP mouse models.

Conclusion: We found that lncRNAs, particularly Neat1, play a significant role in the pathogenesis of AP. This finding may provide new insights into further exploring the pathogenesis of SAP and could lead to the identification of new targets for the treatment of AP and SAP.