Mediators of Inflammation最新文献

Immunoinflammatory responses and macrophage polarisation are crucial for maintaining ovarian function. Moreover, electroacupuncture (EA) has been shown to protect ovarian function. However, the mechanisms by which EA improves ovarian function, including its effects on immunoinflammatory responses and macrophage polarisation, have not been determined. This study aimed to investigate the protective effects of EA on ovarian function in rats with diminished ovarian reserve (DOR) and to elucidate the regulatory mechanisms underlying inflammation and M1 and M2 macrophage polarisation. DOR models were established through the intragastric administration of 50 mg/kg Tripterygium glycoside suspension (TGs) for 14 consecutive days. The EA group received treatment at 2/100 Hz and 1.0 mA for 10 min using acupoints BL23, CV4 and CV12 for 14 days. Following the intervention, we employed various methodologies, including haematoxylin-eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunohistochemical (IHC) staining, western blotting and quantitative reverse transcriptase-polymerase chain reaction (PCR), to assess ovarian function, inflammatory factors and the expression levels of M1 and M2 macrophage-related factors. EA intervention reduced the oestrous cycle disorder rate in the rats compared with that in the DOR group, leading to an increase in growing follicles, a reduction in atretic follicles (AFs) and an enhancement of both the capillary (Cap) network and corpus luteum (CL) structure. This intervention also resulted in decreased serum levels of follicle-stimulating hormone (FSH), interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α), along with increased levels of oestradiol (E₂), interleukin-4 (IL-4) and interleukin-10 (IL-10). Furthermore, the number of M2 macrophages in the spleen increased, which was accompanied by elevated arginase 1 (Arg1) and decreased inducible nitric oxide synthase (iNOS) expression in the ovarian tissues. In summary, EA can restore the impaired ovarian function caused by TGs by promoting M2 macrophage polarisation and inhibiting inflammatory responses.

Background: Dynamin-related protein 1 (DRP1)-dependent mitochondrial fission is a novel target for mitigating inflammatory diseases. This study aims to explore the effects of the DRP1 inhibitor Mdivi-1 on sepsis-induced acute lung injury (ALI). Methods: C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) and then treated with or without Mdivi-1 2 h post-injection. RAW264.7 alveolar macrophages were stimulated with LPS and treated with or without NLRP3 inhibitors, Mito-TEMPO, or Mdivi-1. Hematoxylin and eosin (H&E) staining was used to observe pathological changes in lung tissues. The levels of inflammatory cytokines in lung tissue homogenates, serum, and cell culture medium were detected using enzyme-linked immunosorbent assays (ELISA). The mRNA expression of macrophage polarization markers, NLRP3 activation, and phosphorylation status of DRP1 were assessed. Flow cytometry was employed to evaluate the levels of macrophage apoptosis. Immunofluorescence was utilized to detect the levels of in vivo and in vitro macrophage polarization markers. Mitochondrial reactive oxygen species (Mito-ROS) were measured using a Mito-SOX assay kit. Results: Our results suggested that Mdivi-1 reduced lung tissue pathological injury, M1 alveolar macrophage polarization, NLRP3 activation, and DRP1 Ser616 phosphorylation. In vitro, LPS triggered abnormal accumulation of M1 polarization, NLRP3 activation, and excessive increase in Mito-ROS. NLRP3 inhibitors and Mito-TEMPO inhibited M1 alveolar macrophage polarization and pyroptosis-mediated tissue damage. Mito-TEMPO significantly inhibited NLRP3 activation. Furthermore, Mdivi-1 reduced ALI by inhibiting M1 polarization and pyroptosis. The mechanism of Mdivi-1 in reducing M1 alveolar macrophage polarization and pyroptosis may be related to the inhibition of DRP1-mediated mitochondrial fission, thus suppressing the Mito-ROS/NLRP3 pathway. Similar results were observed in vitro by knocking down DRP1. Conclusion: Inhibition of DRP1 by Mdivi-1 alleviates ALI by hindering Mito-ROS/NLRP3-mediated M1 alveolar macrophage polarization and pyroptosis, suggesting that DRP1-dependent mitochondrial fission is a potential therapeutic target for ALI.

Background: Scoliosis is a condition that can have severe consequences for millions of individuals on an annual basis. Current research in this field is increasingly focusing on the role of the immune system in the development of the disease. However, the precise relationship between immunity and scoliosis remains to be fully elucidated. Method: Our investigation involved a comprehensive Mendelian randomization (MR) analysis to explore the potential causal relationship between immune cells and scoliosis. The comprehensive univariable MR analysis encompassed 731 immune cells to explore their relationship with scoliosis. Cochran's Q test, the leave-one-out test, and MR-Egger intercept analysis were used to assess pleiotropy and heterogeneity. We performed multivariable MR analysis to account for potential confounding factors between the immune cells. The colocalization analysis and summary data-based MR (SMR) analysis were utilized to explore relationship between immune cells and cis-eQTL. Results: Our study identified 13 immune cells that were significantly associated with scoliosis by univariable MR, including four risk factors and nine protective factors for scoliosis. In order to reduce confounding between immune cells, multivariable MR was employed, and it was determined that only six immune cell types had independent effects on scoliosis. SERPINH1 shared the same variant with CX3CR1 on CD14- CD16-. FSD1L shared the same variant with CCR2 on CD14- CD16-. SNHG14, SNORA33, NET1, and SNORD100 shared the same variant with HLA DR on CD14+ CD16+ monocyte. Conclusion: Our findings suggested a possible link between immune cells and scoliosis and found the key genes for the immune cell, which provides a new direction for further research. However, the specific underlying mechanisms require further investigation in future experiments.

Inflammatory/immune cells and mediators are substantial for wound healing because they orchestrate biological activities in this complex process. Among factors that affect wound healing, obesity, and metabolic diseases are among the most significant, particularly because of a relationship between obesity and a prediabetic state with immune reactivity. Using Dark Agouti (DA) and Albino Oxford (AO) rats, which differ in immune responses as well as in proneness to obesity, we examined the impact of these intrinsic factors on cutaneous wound healing. Dynamics of the process were monitored at days 3, 5, and 7 post-wounding parallel in both rat strains by analysis of selected basic aspects of the wound repair process (cytokine and growth factor responses) in granulation tissue. Strain-related differences in the extent of reduction of the wound area were shown, which coincided with differential proinflammatory and immune-regulatory cytokines, as well as growth factors response in these rats. Some of these differences seem related to their dissimilarities in the proneness to obesity. Results in this study extended so far known differences in inflammatory/immune responses to a variety of stimuli between AO and DA rats and showed, for the first time, immune-based differences in wound healing between rats that differ in body mass (BM) and obesity proneness (under ad libitum feeding conditions with normal rodent chow).

Objective: Hypoxia-glycolysis-lactylation (HGL) may play a crucial role in neonatal sepsis (NS). This study aims to identify HGL marker genes in NS and explore immune microenvironment among NS subtypes. Materials and Methods: The gene expression dataset GSE69686, comprising 64 NS cases and 85 controls, was selected for analysis. Based on the screened HGL-related marker genes, diagnostic prediction models were constructed using nine machine learning algorithms, and molecular subtypes of NS were identified through consensus clustering. Subsequently, the heterogeneity of biological functions and immune cell infiltration among the different subtypes was analyzed. Finally, the marker genes and lactylation were validated using the GSE25504 dataset, clinical samples, and mouse neutrophil, respectively. Results: MERTK, HK3, PGK1, and STAT3 were identified and validated as marker genes, and the diagnostic prediction model for NS constructed using the support vector machine (SVM) algorithm exhibited optimal predictive performance. Based on gene expression patterns, two distinct NS subtypes were identified. Functional enrichment analysis highlighted significant immune-related pathways, while immune infiltration analysis revealed differences in neutrophil proportions between the subtypes. Furthermore, the expression levels of marker genes were positively correlated with neutrophil infiltration. Importantly, the experimental validation results were consistent with the findings from the bioinformatics analysis. Conclusion: This study identified the distinct NS subtypes and their associated marker genes. These findings will contribute to elucidating the disease's heterogeneity and establishing appropriate personalized therapeutic approaches.

Background: Periodontitis (PD) and rheumatoid arthritis (RA) are chronic inflammatory conditions, characterized by dysregulated immune response and excessive production of inflammatory mediators. The oral disease PD is triggered by periodontal pathogens, leading to the destruction of tissues surrounding the teeth, whereas RA is a systemic autoimmune disease primarily affecting the joints. The objective of this study was to investigate the prevalence of PD and map the profile of salivary and serum inflammatory mediators of patients with RA, with respect to periodontal severity (PD stage II and PD stage III/IV). Methods: For this cross-sectional cohort study, 62 patients diagnosed with RA were recruited. All participants underwent a full-mouth dental examination. Levels of various inflammatory mediators, including tumor necrosis factor (TNF) superfamily proteins, interferon (IFN) family proteins, regulatory T cell (Treg) cytokines, and matrix metalloproteinases were determined in saliva and serum samples from each participant using a human inflammation multiplex immunoassay panel. Results: In the current RA cohort, all participants were diagnosed with PD, of which 35.5% were classified as PD stage II and 64.5% as PD stages III/IV. Inflammatory mediator levels were significantly higher in both saliva and serum samples from patients with RA and PD stages III/IV, compared to those with RA and stage II within the same cohort. These included higher serum levels of sCD30, IL-10, IL-19, osteopontin and elevated salivary levels of BAFF/TNFSF13B and IFN-α2. Additionally, APRIL/TNFSF13 levels were increased in both saliva and serum. Conclusions: Among the studied patients with RA, the majority exhibited severe PD (stage III/IV), underscoring the importance of periodontal prophylaxis and treatment for this group of patients. Higher levels of inflammatory mediators were observed in both saliva and serum in those with PD stages III/IV, suggesting a potential link between the severity of PD and systemic inflammation in RA. Further research is needed to explore the clinical implications of these findings.

Objective: To investigate whether the histone deacetylase (HDAC) activator ITSA-1 can ameliorate systemic inflammation after cardiac arrest (CA), thereby enhancing cardiac function and neurological outcomes in rats. Materials and Methods: Sixty-nine healthy adult male Wistar rats were subjected to 12 min of CA induced by Vecuronium bromide. The rats were randomly assigned to five groups: normal control, sham operation, control, suberoylanilide hydroxamic acid (SAHA), and ITSA-1. The study evaluated the effects of ITSA-1 on cardiac function, survival, and neurological functions, including the neurological deficit score (NDS) at 24-, 48-, and 72-h post-return of spontaneous circulation (ROSC) and Morris water maze performance at 72 h. Additionally, levels of TNF-α, IL-1β, glial fibrillary acidic protein (GFAP), S100β in plasma, and TNF-α, IL-1β in the hippocampus were measured 4 h post-ROSC. Western blot analysis was used to assess HDACs, nuclear factor kappa B (NF-κB), p-NF-κB, caspase-3, cleaved caspase-3, Bcl-2, and Bax protein expressions. Results: ITSA-1 reduced basic life support (BLS) duration and adrenaline dosage during cardiopulmonary resuscitation (CPR) and improved cardiac and neural functions, enhancing survival compared to the control and SAHA groups. ITSA-1 decreased serum levels of IL-1β, TNF-α, GFAP, S100β, and hippocampal TNF-α, IL-1β, promoting neuronal survival in the CA1 region. It also inhibited glial cell activation and reduced histone acetylation, blocking the NF-κB pathway and neuronal apoptosis. Conclusion: ITSA-1 enhances the recovery and survival of post-ROSC rats by diminishing histone acetylation and mitigating systemic inflammation. This effect is possibly due to the inhibition of glial cell activation, increased neuronal survival in the brain, and improved cardiac output (CO) and ejection fraction (EF).

Objective: The neutrophil-to-lymphocyte ratio (NLR) is an important marker of inflammation. An increased NLR has been detected in the blood of patients with epilepsy. However, the correlation between varying NLRs and epileptic seizures (ESs) is still unclear. Methods: A retrospective analysis was conducted, and patients were divided into two groups based on whether they had ES upon admission. Comprehensive data were collected, including routine blood tests, demographic information, and medical histories. The NLR was calculated by dividing the percentage of neutrophils by the percentage of lymphocytes. Results: In total, 414 patients were included (284 males, 151 females; aged 18-90 years), with 271 in the experimental group and 143 in the control group. No significant differences in the NLR were found between the groups (p=0.164). Nonetheless, when NLRs were categorized, a "V"-shaped link with ES was observed. An NLR of 2-3 correlated with the lowest seizure incidence. Higher NLRs were associated with increased neutrophil and decreased lymphocyte counts. Patients with an NLR < 2 had the lowest infection rates and the highest cerebrovascular disease exposure, whereas those with an NLR > 3 had the highest infection rates and were the oldest. Conclusions: NLR modifications can serve as potential predictive markers for ES. However, the relationship between the NLR and ES is not linear. The factors contributing to these variations are multiple and complex. An NLR of 2-3 may represent an equilibrium point. An elevated NLR indicates pronounced inflammatory responses, while a low NLR can have more complex causes.

According to statistics, more than one-third of the global population currently experiences sleep problems, and about 10% of adults have been diagnosed with insomnia, a proportion that is increasing annually. Most currently used insomnia medications are not specifically developed but are discovered by chance, often resulting in unavoidable side effects like addiction. Thus, there is an urgent need to find safer and more effective therapeutic options. Resveratrol, a natural polyphenolic compound, shows significant potential in improving insomnia. Research shows that its effects may be achieved through multiple biological processes, including antiapoptosis, antioxidant activity, anti-inflammation, circadian rhythm regulation, modulation of neurotransmitters (gamma-aminobutyric acid (GABA), DA, 5-HT, cortisol), and increased levels of neurotrophic factor BDNF. Additionally, resveratrol's treatment of insomnia is closely linked to the SIRT1, AMPK, NF-κB, mTOR, PI3K/Akt, and MAPK pathways. This review summarizes the mechanisms of resveratrol in treating insomnia to provide researchers with a deeper understanding of its action, which can aid in the development of novel targeted drugs and offer innovative ideas and methods for clinical insomnia treatment.

Purpose: The role of the gut microbiomes has been emphasized in the pathogenesis of obese asthma (OA). However, the molecular mechanism of airway dysfunction underlying OA has not yet been fully elucidated. The effects of microbiomes on arginine metabolism in relation to lung functions and a novel method for delivering arginine to lung tissue based on arginine-loaded red blood cell (RBC)-derived nanovesicles (NVs) (NV^Arg) will be investigated. Materials and Methods: Inflammatory status, amino acid profiles, and microbial diversity were evaluated in 20 adult patients with OA compared to 30 adult patients with non-OA (NOA) and 10 healthy control (HC) groups. Changes in gut or lung microbial composition that altered arginine metabolism in relation to airway inflammation were investigated in an OA mouse model in vivo. Additionally, this study evaluated the delivery of arginine to lung tissue utilizing NV^Arg in vivo and in vitro. Results: Significantly increased Bacteroides abundance but decreased serum arginine concentration with lower forced exhaled volume at 1 s (FEV₁) (%) was noted in the OA group compared to the NOA and HC groups. In mouse experiments, when OA mice were given living bacteria from normal control (NC) mice, lung arginine concentration and airway resistance were restored. However, the administration of arginine or its metabolite (citrulline) did not increase the arginine levels in the lung tissues. We therefore created NV^Arg, which successfully delivered arginine into the cytoplasm of the airway epithelial cell line in vitro. Oral administration of NV^Arg for OA mice significantly induced the AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) pathways in airway epithelial cells, which reduced airway resistance and inflammation. Conclusion: These findings suggest that microbiomes contribute to airway dysfunction by regulating arginine metabolism, whereas NV^Arg treatment may be a potential option for managing OA.