Monocyte Chemotactic Protein-1 Levels Research Articles

Correlation of Cytokine Profiles with Prostate-Specific Antigen and Disease Grade in Prostate Cancer.

BACKGROUND The development and progression of prostate cancer are multistep processes involving several growth factors, hormones, and cytokines. This study aimed to measure the serum concentrations of different cytokines and determine their correlation with prostate-specific antigen (PSA) levels and disease grade in patients with prostate adenocarcinoma. MATERIAL AND METHODS This cross-sectional study was conducted from March 2023 to March 2024 at the Clinic of Oncology of the University Hospital Center in Mostar, Bosnia and Herzegovina. Altogether, 50 male patients with prostate adenocarcinoma were included, of whom 28 had no proven metastases (PC group) and 22 had metastatic disease (MPC group). Serum concentrations of total (tPSA), free (fPSA), and complexed (cPSA) PSA were determined using a chemiluminescent microparticle immunoassay, whereas serum concentrations of cytokines were measured using a flow cytometry bead-based assay. RESULTS The MPC group had higher serum tPSA, fPSA, and cPSA levels than the PC group. The PC group had significantly higher serum levels of monocyte chemotactic protein (MCP)-1 than the MPC group (P=0.008). In the PC group, serum levels of interleukin (IL)-10 significantly correlated with cPSA. In the MPC group, serum concentrations of IL-1ß, tumor necrosis factor (TNF)-alpha, and IL-23 significantly correlated with disease grade. CONCLUSIONS Our study emphasizes the importance of MCP-1 in the development of prostate cancer, while IL-10 was the only cytokine whose serum level significantly correlated with cPSA. Serum concentrations of IL-1ß, TNF-alpha, and IL-23 may serve as potential biomarkers for disease grade.

Effective Assessment of Rheumatoid Arthritis Disease Activity and Outcomes Using Monocyte Chemotactic Protein-1 (MCP-1) and Disease Activity Score 28-MCP-1.

The effectiveness of monocyte chemotactic protein-1 (MCP-1) and Disease Activity Score 28 (DAS28)-MCP-1 (DAS28-MCP-1) in assessing rheumatoid arthritis (RA) disease activity is unclear, although some studies have demonstrated their potential usefulness. The present study investigated relationships between MCP-1 and different DAS28 measures, the occurrence of residual swollen joints in different DAS28 remission statuses, changes in medication dosage in relation to the 2005 modified American Rheumatism Association and 2011 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) remission definitions, and the correlations between different DAS28-related scores and Health Assessment Questionnaire Disability Index (HAQ-DI) scores in two RA patient cohorts. The results revealed that the MCP-1 level was correlated with five disease activity measures (DAS28-erythrocyte sedimentation rate [DAS28-ESR], DAS28-C-reactive protein [CRP], Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and DAS28-MCP-1) in multivariable regression analysis (all p < 0.05; ESR, CRP, and MCP-1 as independent variables). However, ESR was not significantly associated with SDAI and CDAI scores (p = 0.343 and 0.323, respectively). Residual swollen joints were more frequently observed in patients who met the DAS28-ESR remission criteria (<2.6) compared with those meeting the other four remission criteria, with a difference ranging from 71% to 94%. Among patients meeting the DAS28-ESR remission criteria (<2.6), medication changes (dose increase by ≥30% or new medications prescribed) were less frequent in those who also met the 2011 ACR/EULAR remission criteria than in those who did not meet them (p = 0.006). Moreover, the correlation coefficients for the relationship between DAS28-ESR and HAQ-DI scores were the lowest among the five disease activity measures. In conclusion, MCP-1 and DAS28-MCP-1 are effective in assessing RA disease activity, with less residual joint swelling and less frequent medication increases observed in the DAS28-MCP-1 remission < 2.2 subgroup.

Effect of Preoperative Glucocorticoid Application on Vitreous Parthanatos-Related Protein Expression in Patients with Rhegmatogenous Retinal Detachment Associated with Choroidal Detachment

Purpose The protein concentrations of apoptosis inducing factor (AIF), macrophage migration inhibitory factor (MIF), interleukin-1β (IL-1β), poly ADP ribose polymerase-1 (PARP-1), poly (ADP-ribose) (PAR), α-synuclein (α-SYN), monocyte chemotactic protein‑1 (MCP-1) and tumor necrosis factor-α (TNF-α) in the vitreous of eyes with rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD) were observed and analyzed. Methods A total of 57 patients’ samples were included. 30 patients with RRD were set as the control group, 27 patients with RRDCD were set as the experimental group (16 patients with preoperative glucocorticosteroid (GC+) and 11 patients without preoperative glucocorticosteroid (GC−)). The levels of AIF, MIF, IL-1β, PARP-1, PAR, α-SYN, MCP-1 and TNF-α in vitreous of patients in the control and experimental groups were detected by enzyme-linked immunosorbent assay (ELISA). Results The concentration of AIF in the vitreous was higher in the RRD group (9.96 ± 2.78 ng/ml) than in the RRDCD (GC+) group (7.65 ± 2.13 ng/ml, p = 0.006),the RRDCD (GC+) group was lower than the RRDCD (GC−) group (10.28 ± 2.81 ng/ml) (p = 0.013). The concentration of MIF in vitreous fluid was lower in the RRDCD (GC+) group (61.21 ± 17.56 ng/ml) than in the RRDCD (GC−) group (74.30 ± 9.66 ng/ml, p = 0.039). In the experimental group, the protein concentration of MCP-1 in the RRDCD (GC+) group was higher in the preoperative PVR grading C (284.93 ± 54.96 ng/ml) grade than in the D grade (225.94 ± 24.05 ng/ml) (p = 0.050); The protein concentration of MIF was lower in the RRDCD (GC+) group of patients with an ocular axis of <26 mm (56.19 ± 6.99 ng/ml) than in those with an ocular axis of ≥26 mm (76.26 ± 26.60 ng/ml, p = 0.043). Conclusion Low expression of Parthanatos-related proteins is present in the vitreous of patients with RRDCD (GC+), and preoperative treatment with glucocorticoids may reduce the expression of Parthanatos-related proteins.

Effects of Immunotoxicity biomarkers, essential elements and vitamin D levels on the severity levels of COVID-19 disease in Turkey.

Many mechanisms are thought to play a role in the pathogenesis of the COVID-19 pandemic, which started in 2019 and affected the whole world. It has been claimed that a deficiency in the immune system can significantly affect the severity of COVID-19 disease. It is important that the levels of essential elements and vitamin D are at certain levels for the healthy functioning of the immune system. Therefore, in this study, it was aimed to evaluate immunotoxicity biomarkers (tumor necrosis factor-alpha (TNF-α), interleukin (IL)-10, interferon (IFN)-γ, monocyte chemotactic protein-1 (MCP-1)), vitamin D, and essential element levels in COVID-19 patients in Turkey. According to the results of the study, it was found that the magnesium (Mg), zinc (Zn), and selenium (Se) levels decreased as the severity of the disease worsened, while the iron (Fe), and copper (Cu) levels were similar to the mild group and the control group, and the levels decreased as the disease worsened. It has also been found that vitamin D levels decrease as the severity of the disease worsens. Compared to the control group, TNF-α, MCP-1, and IFN-γ levels were found to decrease as the severity of the disease worsened. Also, it was observed that there was a significant relationship between essential metal levels and disease progression in most of the patient groups.

Leptin limits hepatic lipid accumulation and inflammation via vagal activation of the JAK2-STAT3/AMPK pathway

Non-Alcoholic Fatty Liver Disease (NAFLD) begins with hepatic lipid accumulation, and leptin has antisteatosis properties. In this study, we investigated the effects of leptin on hepatic steatosis and inflammation through the vagal pathway independently of the inhibitory effect of food intake. Male Sprague-Dawley rats were matched for food intake after the high-fat diet (HFD)-induced obesity model and were injected intraperitoneally with leptin or leptin + lidocaine for 6 weeks. Control rats received equal volumes of saline. Adipose tissue mass, NAFLD activity scores (NAS), hepatic inflammatory factors, hepatic triglyceride content and hepatic lipid metabolism-related protein levels were evaluated. Leptin ameliorated HFD-induced hepatic lipid accumulation, improved NAS, and decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) levels in the presence of matched intake. Lidocaine decreased the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) expression in the nucleus tractus solitarius (NTS) and abrogated the leptin-mediated improvement. Leptin increased hypothalamic phosphorylated Janus kinase 2 (p-JAK2) and p-STAT3 expression, as well as the expression of mitochondrial respiratory chain-related genes. Leptin also increased hepatic phosphorylated adenosine 5′-monophosphate-activated protein kinase (p-AMPK) expression and phosphorylation of its downstream target acetyl Co A carboxylase 1 (ACC1), reducing de novo lipogenesis. Our results suggest that leptin ameliorated hepatic lipid accumulation and inflammation by activating the JAK2-STAT3/AMPK pathway through the vagal pathway independently of the inhibitory effect of ingestion. Leptin has the potential to be a drug for early NAFLD treatment.

Causal effect of circulating cytokines on MRI markers of cerebral small vessel disease: A mendelian randomization study

BackgroundPrevious observational studies have reported the correlation between circulating inflammatory cytokines and cerebral small vessel disease (CSVD). However, the causality of this association is uncertain. This study used Mendelian randomization to investigate the causal effect of circulating inflammatory cytokines on neuroimaging changes in CSVD. MethodsThis study utilized genetic variances of 41 inflammatory cytokines and 3 neuroimaging markers of CSVD from genome-wide association studies to assess the causal effects in a two-sample Mendelian randomization approach. Inverse variance weighted analysis was used as the main analytical method, and sensitivity analysis was used to further validate the robustness of the results. ResultsIncreased IL-18 was associated with increased white matter hyperintensity (WMH) and mean diffusivity (MD) (β = 0.034, 95 % CI 0.002, 0.065, P=0.038, β = 0.157, 95 % CI 0.015, 0.299, P=0.030). However, increased IL-18 was associated with decreased fractional anisotropy (FA) (β = -0.141, 95 % CI −0.279, −0.002, P=0.047). Increased monocyte chemotactic protein-1(MCP-1) was associated with decreased FA (β = -0.278, 95 % CI −0.502, −0.054, P=0.015). Increased IL-10 levels and IL-2ra levels were associated with decreased risks of MD (β = -0.228, 95 % CI −0.448, −0.009, p = 0.041; β = -0.204, 95 % CI=-0.377, −0.031, p = 0.021). ConclusionsThis study revealed that increased levels of IL-18 and MCP-1 were associated with white matter microstructural injury, and increased levels of IL-10 and IL-2ra were associated with decreased MD.

Effects of Venoactive Drug Therapy and Ovarian Vein Interventions on Vasoactive Neuropeptide and Cytokine Levels in Patients with Pelvic Venous Disorders

To study and compare the effects of venoactive drug (VAD) therapy and ovarian vein embolization or resection (OVE or OVR, accordingly) on the levels of vasoactive peptides and cytokines in patients with pelvic venous disorders (PeVDs). The study included 70 consecutive female patients with PeVD symptoms, such as chronic pelvic pain (CPP), dyspareunia, dysuria, and vulvar varicosities. Based on the results of clinical examination and duplex ultrasound of the pelvic veins, the patients were allocated to the VAD therapy (n=38) or OVE/OVR (n=32). Additionally, the enzyme-linked immunosorbent assay tests were performed to determine levels of calcitonin gene-related peptide (CGRP), substance P (SP), interleukins 6 and 8 (IL-6, IL-8) and monocyte chemotactic protein-1 (MCP-1) after a 2-month course of VAD therapy and at 3months after OVE/OVR. The VAD therapy was associated with a significant decrease in CPP in 84% of patients with PeVD and isolated lesions of the parametrial veins (PVs) and uterine veins (UVs). VAD had no significant effect on the pelvic venous reflux. No changes in the CGRP, SP, IL-6, IL-8, and MCP-1 levels were detected after treatment. At 3months after OVE or OVR, all patients with PeVD and combined lesions of the ovarian veins (OVs), PVs and UVs reported almost complete relief of CPP. Along with elimination of reflux in ovarian veins, the disappearance of reflux in PVs and UVs was noted. A decrease in the CGRP and SP levels was observed (0.7±0.1ng/mL and 0.12±0.02ng/mL before treatment; 0.5±0.12ng/mL and 0.09±0.06ng/mL after treatment, respectively; all P<0.05). No changes in cytokine levels were revealed. Treatment with VAD is associated with the CPP relief, but has no significant effect on the CGRP, SP, IL-6, IL-8, and MCP-1 levels. OVE/OVR results in the CPP relief, elimination of the pelvic venous reflux and a significant decrease in the CGRP and SP levels, but does not change cytokine levels.

Correlation of circulating fibroblast growth factor 21 levels with inflammatory factors and the degree of coronary artery stenosis in patients with acute myocardial infarction

BackgroundFibroblast growth factor 21 (FGF21) is a secreted protein that plays an important role in atherosclerosis and pathological cardiac remodeling. However, the correlation between FGF21 and the degree of coronary artery stenosis and its potential role in acute myocardial infarction (AMI) remain unclear. We examined whether changes in FGF21 levels in AMI correlate with the degree of coronary artery stenosis and the levels of inflammatory factors, and preliminarily investigated the effects of FGF21 on inflammatory factor levels and myocardial injury in rats with AMI. MethodsSerum levels of FGF21 and inflammatory factors in the AMI group and control group were measured, and the correlation between FGF21 and clinical indicators and inflammatory factors was analyzed. The effects of FGF21 on cardiac function and inflammatory response were evaluated through echocardiography and measurement of inflammatory factors. ResultsMultivariate logistic regression analysis showed that neutrophil percentage (NEUT%, odds ratio [OR]: 1.232; 95 % confidence interval [CI]: 1.028–1.477; p = 0.024) and FGF21 levels (OR: 2.063; 95 % CI: 1.187–3.586; p = 0.01) had independent effects on AMI. Spearman's rank correlation test showed that FGF21 levels were positively correlated with leukocyte count, NEUT%, neutrophil count, neutrophil to lymphocyte ratio, C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1) and Gensini scores (p < 0.01), but negatively correlated with lymphocyte count (p < 0.01). FGF21 levels in myocardial tissues and serum levels of FGF21, IL-6, TNF-a, and MCP-1 were significantly higher in AMI rats than in the sham-operated group (p < 0.01). After overexpression of FGF21, serum levels of IL-6, TNF-a, and MCP-1 in rats were significantly decreased (p < 0.01), and cardiac function improved significantly. ConclusionsFGF21 levels were independently associated with AMI and may be related to the severity of coronary artery stenosis. Overexpression of FGF21 reduced serum inflammatory factor levels and improved cardiac function in AMI rats.

Causal relationship between inflammatory cytokines and autoimmune thyroid disease: a bidirectional two-sample Mendelian randomization analysis.

Autoimmune thyroid disease (AITD) ranks among the most prevalent thyroid diseases, with inflammatory cytokines playing a decisive role in its pathophysiological process. However, the causal relationship between the inflammatory cytokines and AITD remains elusive. A two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal connection between AITD and 41 inflammatory cytokines. Genetic variations associated with inflammatory cytokines were sourced from the FinnGen biobank, whereas a comprehensive meta-analysis of genome-wide association studies (GWASs) yielded data on Graves' disease (GD) and Hashimoto thyroiditis. Regarding the MR analysis, the inverse variance-weighted, MR-Egger, and weighted median methods were utilized. Additionally, sensitivity analysis was conducted using MR-Egger regression, MR-pleiotropy residual sum, and outliers. Seven causal associations were identified between inflammatory cytokines and AITD. High levels of tumor necrosis factor-β and low levels of stem cell growth factor-β were indicative of a higher risk of GD. In contrast, high levels of interleukin-12p70 (IL-12p70), IL-13, and interferon-γ and low levels of monocyte chemotactic protein-1 (MCP-1) and TNF-α suggested a higher risk of HD. Moreover, 14 causal associations were detected between AITD and inflammatory cytokines. GD increases the levels of macrophage inflammatory protein-1β, MCP-1, monokine induced by interferon-γ (MIG), interferon γ-induced protein 10 (IP-10), stromal cell-derived factor-1α, platelet-derived growth factor BB, β-nerve growth factor, IL-2ra, IL-4, and IL-17 in blood, whereas HD increases the levels of MIG, IL-2ra, IP-10, and IL-16 levels. Our bidirectional MR analysis revealed a causal relationship between inflammatory cytokines and AITD. These findings offer valuable insights into the pathophysiological mechanisms underlying AITD.

Killer Function of Circulating Neutrophils in Relation to Cytokines in Uterine Myoma and Endometrial Cancer.

The study presents the killer functions of circulating neutrophils: myeloperoxidase activity, the ability to generate ROS, phagocytic activity, receptor status, NETosis, as well as the level of cytokines IL-2, IL-4, IL-6, IL-17A, and IL-18, granulocyte CSF, monocyte chemotactic protein 1, and neutrophil elastase in the serum of patients with uterine myoma and endometrial cancer (FIGO stages I-III). The phagocytic ability of neutrophils in uterine myoma was influenced by serum levels of granulocyte CSF and IL-2 in 54% of the total variance. The degranulation ability of neutrophils in endometrial cancer was determined by circulating IL-18 in 50% of the total variance. In uterine myoma, 66% of the total variance in neutrophil myeloperoxidase activity was explained by a model dependent on blood levels of IL-17A, IL-6, and IL-4. The risk of endometrial cancer increases when elevated levels of monocyte chemotactic protein 1 in circulating neutrophils are associated with reduced ability to capture particles via extracellular traps (96% probability).

The effect of leizumab on serum vascular endothelial growth factor, IL-6, MCP-1 inflammatory factors in neovascular glaucoma.

This study aimed to assess Leizumab's effect on serum endothelial growth factor, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and inflammatory factors in neovascular glaucoma patients. 80 eligible patients treated between January 2021 and April 2023 were enrolled, randomly divided into control and study groups. The control group underwent vitrectomy while the study group received preoperative intravitreal rituximab injection. Measurements included serum and aqueous humor VEGF/PEDF, IL-6/MCP-1 levels, postoperative rebleeding/retinal detachment, and visual acuity changes over 6 weeks. After surgery, patients showed reduced serum VEGF/PEDF levels (P < 0.05), with decreased VEGF and increased PEDF in aqueous humor (P < 0.05). The study group had lower VEGF and higher PEDF levels than the control (P < 0.05). Serum IL-6/MCP-1 levels reduced post-surgery, with the study group lower than control (P < 0.05). Intraocular rebleeding was lower in the study group (P < 0.05), while retinal detachment rates were similar (P > 0.05). Visual acuity differed significantly from week 1 to 6 post-surgery (P < 0.05), with higher acuity in the study group during weeks 1-4 (P < 0.05). Weeks 5-6 follow-up showed no significant difference (P > 0.05). Pre-vitrectomy ranibizumab injection effectively reduced bleeding, VEGF/PEDF levels, inflammatory factors, and improved visual recovery.

Cytokine Signatures for Lung Cancer Diagnosis in African American Populations.

Lung cancer is the leading cause of cancer-related deaths among both men and women. African Americans (AAs) experience disproportionately higher incidence and mortality compared to other ethnic groups. Cytokines play multifaceted and crucial roles in the initiation, progression, and spread of cancer. Our aim was to identify cytokine biomarkers for the early detection of lung cancer in AAs. We examined eight key cytokines (Interleukin-1, IL-6, IL-8, IL-10, IL-12p70, monocyte chemotactic protein-1 (MCP-1), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α)) in the plasma of 104 lung cancer patients and 48 cancer-free individuals using the FirePlex Immunoassay. These findings were subsequently validated in a separate cohort of 58 cases and 58 controls. IL-8, IFN-γ, and TNF-α exhibited elevated levels in both AA and White American (WA) lung cancer cases. Notably, IL-10 and MCP-1 displayed significant increases specifically in AA lung cancer patients, with MCP-1 levels associated with lung adenocarcinoma cases. Conversely, WA lung cancer patients showed heightened IL-6 levels, particularly linked to lung adenocarcinoma. The combined use of specific cytokines showed promise in lung cancer diagnosis, with IL-8, IL-10, and MCP-1 achieving 76% sensitivity and 79% specificity in AAs and IL-6 and IL-8 combined offering 76% sensitivity and 74% specificity in WAs. These diagnostic biomarkers were validated in the independent cohort. The ethnicity-related cytokine biomarkers hold promise for diagnosing lung cancer in AAs and WAs, potentially addressing the observed racial disparity.

Serum monocyte chemotactic protein 1 and soluble mannose receptor aid predictive diagnosis of pediatric sepsis.

To investigate the value of serum monocyte chemotactic protein 1 (MCP-1) and soluble mannose receptor (sMR) for predictive diagnosis of pediatric sepsis. This study retrospectively analyzed the data of 82 children with acute and severe signs of inflammation. According to the diagnostic criteria of sepsis, these children were divided into a sepsis group (40 cases) and a non-sepsis group (42 cases). In addition, 50 children who received health examinations during the same time period in Cangzhou Central Hospital were selected as a control group. According to the prognosis of the children in the sepsis group, they were further divided into a survival group (33 cases) and a death group (7 cases). The levels of blood indicators, inflammatory markers, liver and kidney function indicators, MCP-1 level, and sMR were collected from the children. The efficacy of using sMR and MCP-1 levels in the predictive diagnosis of sepsis was analyzed by using the area under the ROC curve (AUC). Serum levels of MCP-1 and sMR were (452.32±2.79) μg/ml and (97.23±.15) μg/ml, respectively, in the sepsis group, significantly higher than those in all controls (P<0.001). In the death group, the levels of white blood cells (WBC), C-reactive protein (CRP), procalcitonin (PCT), sMR, and MCP-1 were significantly higher compared to the survival group (P<0.05). The AUC for CRP in predictive diagnosis of sepsis was 0.9075; the AUC for PCT was 0.8759; the AUC for sMR was 0.9244; and the AUC for MCP-1 was 0.9406. Serum sMR and MCP-1 levels can help predict the diagnosis of pediatric sepsis.

Evaluation of inflammatory biomarkers and their association with anti-SARS-CoV-2 antibody titers in healthcare workers vaccinated with BNT162B2.

Vaccine-induced immunity against COVID-19 generates antibody and lymphocyte responses. However, variability in antibody titers has been observed after vaccination, and the determinants of a better response should be studied. The main objective of this investigation was to analyze the inflammatory biomarker response induced in healthcare workers vaccinated with BNT162b2, and its association with anti-Spike (a SARS-CoV-2 antigen) antibodies measured throughout a 1-year follow-up. Anti-spike antibodies and 92 biomarkers were analyzed in serum, along with socio-demographic and clinical variables collected by interview or exploration. In our study, four biomarkers (ADA, IL-17C, CCL25 and CD8α) increased their expression after the first vaccine dose; and 8 others (uPA, IL-18R1, EN-RAGE, CASP-8, MCP-2, TNFβ, CD5 and CXCL10) decreased their expression. Age, body mass index (BMI), smoking, alcohol consumption, and prevalent diseases were associated with some of these biomarkers. Furthermore, higher baseline levels of T-cell surface glycoprotein CD6 and hepatocyte growth factor (HGF) were associated with lower mean antibody titers at follow-up, while levels of monocyte chemotactic protein 2 (MCP-2) had a positive association with antibody levels. Age and BMI were positively related to baseline levels of MCP-2 (β=0.02, 95%CI 0.00-0.04, p=0.036) and HGF (β=0.03, 95%CI 0.00-0.06, p=0.039), respectively. Our findings indicate that primary BNT162b2 vaccination had a positive effect on the levels of several biomarkers related to T cell function, and a negative one on some others related to cancer or inflammatory processes. In addition, a higher level of MCP-2 and lower levels of HGF and CD6 were found to be associated with higher anti-Spike antibody titer following vaccination.

Accumulation of Inflammatory Mediators in the Normal Pericardial Fluid.

There is paucity of studies that focus on the composition of pericardial fluid under resting conditions. The purpose of this study is to determine the levels of inflammatory mediators in pericardial fluid and their correlation with plasma levels in patients undergoing elective cardiac surgery. We conducted a prospective cohort study on candidates for elective aortic valve replacement surgery. Pericardial fluid and peripheral venous blood samples were collected after opening the pericardium. Levels of interleukin 1α (IL-1α); interleukin 1β (IL-1β); interleukin 2 (IL-2) interleukin 4 (IL-4); interleukin 6 (IL-6); interleukin 8 (IL8); interleukin 10 (IL10); tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in both pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included of which 66% were males. Serum levels of all study mediators were within normal limits. Serum and pericardial levels of IL-1 α, IL-1 β, IL-2, IL-4, and IL-10 were similar. Levels of VEGF, EGF, VCAM-2, ICAM 1, E-selectin, P-selectin, and L-selectin were significantly lower in pericardial fluid than in serum. However, levels of IL-6, IL-8, TNF-α, IFN-γ, MCP-1, and MCP-1 were significantly higher in the pericardial fluid than in serum. Under normal conditions, the pattern of distribution of different inflammatory mediators in the pericardial fluid does not reflect serum levels. This may either reflect the condition of the underlying myocardium and epicardial fat or the activity of the mesothelial and mononuclear cells present in pericardial fluid.

Amelioration of Atherosclerosis by lycopene is linked to the modulation of gut microbiota dysbiosis and related gut-heart axis activation in high-fat diet-fed ApoE−/− mice

BackgroundInterplay between gut microbiota and heart, termed “gut-heart” axis, has a crucial role in the pathogenesis of atherosclerosis. Our previous study showed that lycopene possesses anti-inflammatory and anti-atherosclerotic effects, but its link to the gut microbiota is poorly understood. Herein, we surmised that lycopene could regulate the gut microbiota, exert anti-atherosclerotic effect by regulating the “gut-heart” axis.MethodsMale ApoE−/− mice were fed a high-fat diet (HFD) with or without lycopene (0.1% w/w) for 19 weeks. Gut microbiota was analyzed by 16 S rRNA sequencing, the protein levels of zonula occludens-1 (ZO-1), occludin, toll-like receptor 4 (TLR4) and phospho-nuclear factor-κB (NF-κB) p65 were measured by Western blotting, the levels of serum inflammatory factors including monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 were assayed using ELISA kits. Also, the concentrations of serum lipopolysaccharide (LPS), D-lactic acid (D-LA) and diamine peroxidase (DAO) were measured through ELISA method.ResultsThe aortic sinus sections revealed that lycopene supplementation significantly reduced the extent of atherosclerotic lesions and inhibited atherosclerosis development caused by HFD. The analysis of gut microbiota showed that lycopene reduced the ratio of Firmicutes/Bacteroides and increased the relative abundance of Verrucomicrobia, Akkermansia and Alloprevotella, which were related to elevated intestinal barrier function and reduced inflammation. Moreover, lycopene up-regulated the expression of intestinal ZO-1 and occludin and decreased serum LPS, D-LA and DAO levels. In addition, lycopene inhibited the expression of TLR4 and phospho-NF-κB p65 in aortic sinus plaque, serum MCP-1, TNF-α, IL-1β, and IL-6 levels were also lowered by lycopene treatment.ConclusionsOur results indicated the protective effect of lycopene against atherosclerosis induced by HFD and further revealed that its mechanism might be its prebiotic effect on maintaining gut microbiota homeostasis and improving intestinal barrier function, consequently reducing serum LPS-triggered inflammatory response in the heart.

Microvascular activation and exocytosis after exposure to the serum from mismatched recipients by using donor microvascular cultures

BackgroundMicrovascular injury resulting from activation and exocytosis are early signs of tissue damage caused by allografting. However, humoral anti-graft reactions are not easily detectable in transplant biopsies. The aim of this study was to establish a bioassay to recapitulate this process in a prospective approach. MethodsThe study was executed by using our previously established protocol to isolate and freeze the donors' microvascular endothelial cells (MVEC) at the transplantation (34 living-related donors and 26 cadaver donors); and to collect sera from the recipients before the transplantation, one-, three- and six-months after transplantation. The activation and exocytosis of the MVEC were determined by incubating the donors' cultures with the recipients' sera. We determined if there was any endothelial activation by quantifying the releases of monocyte chemotactic protein-1 (MCP-1) and interleukin 8 (IL-8) in supernatants and the expressions of membrane intercellular adhesion molecule-1 (CD54) and intercellular adhesion molecule-1 (CD106) by flow cytometry. Endothelial exocytosis was determined by quantifying soluble E-selectin (CD62E) and cytoplasmic von Willebrand Factor (vWF) in supernatants. Endothelial activation or exocytosis was considered positive when the fold change (≧1.5) of post-transplantation to pre-transplantation was reached. We also monitored serum PRA and cytokines using Luminex multiple-plex and cytometric bead-based assay respectively. ResultsWe found 41.2% recipients (14 out of 34, ranging from 1.5 to 5.2 folds, p < 0.05) exhibited positive MVEC activation in the first month after transplantation as determined by IL-8 levels; 26.5% recipients (9 out of 34, ranging from 1.5 to 11.8 folds, p < 0.05) by MCP-1 levels. In the group of three months post-transplantation, 70.6% patients were positive (12 out of 17, ranging from 1.8 to 87.1 folds, p < 0.05) by IL-8 increased levels; 24% recipients (4 out of 17, ranging from 1.8 to 50.5 folds, p < 0.05) measured by MCP-1 levels. However, these changes disappeared six months after transplantation. Flow cytometric data showed that a time-dependent of CD54+ and CD106+ expressions existed over the course of six months. Most CD54+ and CD106+ cells were CD31- (platelet-endothelial cell adhesion molecule-1), though CD31+/CD106+ (37.5%, 3 out of 8) and CD31+/CD106+ (25%. 2 out of 8) were seen. When comparing donor MVEC activation to their recipient's proinflammatory cytokine levels or PRA status, we could not draw a conclusion regarding the connections between them. The sera collected from recipients at either one- or three-months after allografting did not significantly induce the release of either soluble CD62E or vWF (p > 0.05), indicating exocytosis was not significantly involved in the acute phase of allografting. ConclusionsThis bioassay enables us to detect the activation and exocytosis of donor MVEC elicited by respective sera from mismatched kidney recipients.

Effect and mechanism of ubiquitin-like protein FAT10 on AngⅡ induced endothelial cell inflammation

Objective: To investigate the role and related mechanism of ubiquitin-like protein FAT10 in the angiotensin Ⅱ (AngⅡ)-induced endothelial cell inflammatory responses. Methods: The Western blot was used to detect the protein expression of FAT10 in 16-weeks old WKY rat carotid artery, thoracic aorta artery, renal artery and vascular smooth muscle cells (VSMC), human umbilical vein endothelial cells (HUVEC) and human breast cancer cells (MDA-MB-231). The optimal concentration and stimulation time of AngⅡ on inducing the highest FAT10 in HUVEC were determined. The following plasmids were constructed: control plasmid, overexpression FAT10 plasmid (Flag-FAT10), invalid interference plasmid, and interference FAT10 plasmid (sh-FAT10). These plasmids were then transfected into HUVEC cells and divided into following groups: control group, Flag-FAT10 group, invalid interference group, and sh-FAT10 group. After culturing with 100 nmol/L AngⅡ for 36 h, the control group and the Flag-FAT10 group were treated with reactive oxygen species scavenger N-acetyl-L-cysteine ​​(NAC), the protein expression levels of the inflammatory factor monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) were measured. Laser confocal microscopy was used to detect the generation levels of reactive oxygen species in the cells of vrious groups. Results: FAT10 was expressed in carotid artery, thoracic aorta, and renal artery of normal blood pressure rats and expressed in HUVEC, VSMC, MDA-MB-231. The expression level of FAT10 gradually increased in proportion to the increase of the time and concentration of AngⅡ stimulation in HUVEC, and the expression level of FAT10 was the highest when the HUVEC was treated with 100 nmol/L AngⅡ for 36 h (P<0.01). The protein expression level of MCP-1 (P<0.001) and TNF-α (P<0.01) was higher in AngⅡ treated HUVEC with FAT10 overexpression, while the expression level of MCP-1 and TNF-α protein was lower in AngⅡ treated HUVEC with FAT10 knockdown (all P<0.01). The level of intracellular reactive oxygen species (ROS) production was significantly increased with FAT10 overexpression (P<0.001), and the level of ROS was decreased when the expression of FAT10 was interfered (P<0.05). The increased level of MCP-1 and TNF-α proteins in FAT10 overexpressed HUVEC was reversed by NAC (all P<0.05). Conclusion: FAT10 promotes the release of inflammatory factors induced by AngⅡ in endothelial cells by increasing the level of intracellular ROS production.

Increased expression of the P2Y12 receptor is involved in the failure of autogenous arteriovenous fistula caused by stenosis

Objective This study investigated the role of the P2Y12 receptor in autogenous arteriovenous fistula (AVF) failure resulting from stenosis. Methods Stenotic venous tissues and blood samples were obtained from patients with end-stage renal disease (ESRD) together with AVF stenosis, while venous tissues and blood samples were collected from patients with ESRD undergoing initial AVF surgery as controls. Immunohistochemistry and/or immunofluorescence techniques were utilized to assess the expression of P2Y12, transforming growth factor-β1 (TGF-β1), monocyte chemotactic protein 1 (MCP-1), and CD68 in the venous tissues. The expression levels of P2Y12, TGFβ1, and MCP-1 were quantified using quantitative reverse transcription–polymerase chain reaction and western blot analyses. Double and triple immunofluorescence staining was performed to precisely localize the cellular localization of P2Y12 expression. Results Expression levels of P2Y12, TGFβ1, MCP-1, and CD68 were significantly higher in stenotic AVF venous tissues than in the control group tissues. Double and triple immunofluorescence staining of stenotic AVF venous tissues indicated that P2Y12 was predominantly expressed in α-SMA-positive vascular smooth muscle cells (VSMCs) and, to a lesser extent, in CD68-positive macrophages, with limited expression in CD31-positive endothelial cells. Moreover, a subset of macrophage-like VSMCs expressing P2Y12 were observed in both stenotic AVF venous tissues and control venous tissues. Additionally, a higher number of P2Y12 +/TGF-β1+ double-positive cells were identified in stenotic AVF venous tissues than in the control group tissues. Conclusion Increased expression of P2Y12 in stenotic AVF venous tissues of patients with ESRD suggests its potential involvement in the pathogenesis of venous stenosis within AVFs.

Pathological roles of bone marrow adipocyte-derived monocyte chemotactic protein-1 in type 2 diabetic mice.

Type 2 diabetes mellitus (T2DM) has become a prevalent public health concern, with beta-cell dysfunction involved in its pathogenesis. Bone marrow adipose tissue (BMAT) increases in both the quantity and area in individuals with T2DM along with heightened monocyte chemotactic protein-1 (MCP-1) secretion. This study aims to investigate the influence and underlying mechanisms of MCP-1 originating from bone marrow adipocytes (BMAs) on systemic glucose homeostasis in T2DM. Initially, a substantial decrease in the proliferation and glucose-stimulated insulin secretion (GSIS) of islet cells was observed. Moreover, a comparative analysis between the control (Ctrl) group and db/db mice revealed significant alterations in the gene expression profiles of whole bone marrow cells, with a noteworthy upregulation of Mcp-1. And the primary enriched pathways included chemokine signaling pathway and AGE-RAGE signaling pathway in diabetic complications. In addition, the level of MCP-1 was distinctly elevated in BMA-derived conditional media (CM), leading to a substantial inhibition of proliferation, GSIS and the protein level of phosphorylated Akt (p-Akt) in Min6 cells. After blocking MCP-1 pathway, we observed a restoration of p-Akt and the proliferation of islet cells, resulting in a marked improvement in disordered glucose homeostasis. In summary, there is an accumulation of BMAs in T2DM, which secrete excessive MCP-1, exacerbating the abnormal accumulation of BMAs in the bone marrow cavity through paracrine signaling. The upregulated MCP-1, in turn, worsens glucose metabolism disorder by inhibiting the proliferation and insulin secretion of islet cells through an endocrine pathway. Inhibiting MCP-1 signaling can partially restore the proliferation and insulin secretion of islet cells, ultimately ameliorating glucose metabolism disorder. It's worth noting that to delve deeper into the impact of MCP-1 derived from BMAs on islet cells and its potential mechanisms, it is imperative to develop genetically engineered mice with conditional Mcp-1 knockout from BMAs.