Search Results (171)

Preeclampsia, one of the leading causes of maternal and fetal morbidity and mortality, affects approximately 3–5% of pregnancies worldwide. However, its etiology remains poorly understood. The aim of this study was to identify molecular markers of preeclampsia. Protein concentrations in blood and urine were determined using the Bio-Plex Kidney Toxicity 1 assay Bio-Rad, Hercules, CA, USA followed by magnetic separation and flow cytometry. This study included 51 patients with preeclampsia and 25 healthy pregnant women. The results revealed that five out of the six serum biomarkers of kidney injury were elevated in the preeclampsia group compared to the control group (calbindin 1, clusterin, glutathione transferase pi (GSTP1), monocyte chemotactic protein 1 (MCP-1), and kidney injury molecule type 1 (KIM-1)). Additionally, the serum concentrations of calbindin 1, clusterin, GSTP1, and KIM-1 were significantly higher in both early-onset and late-onset preeclampsia compared to the control group. The analysis of urinary proteins showed that only the KIM-1 concentration was elevated in late-onset preeclampsia compared to the control group. These findings suggest that the calbindin 1, clusterin, GSTP1, KIM-1, and MCP-1 concentrations in maternal plasma could serve as potential biomarkers for monitoring kidney injury in preeclamptic women. This study provides a foundation for future research to explore novel biomarkers of preeclampsia and renal injury in pregnant women. Full article

Childhood obesity and overweight are linked to subclinical inflammatory conditions. The present manuscript aimed to undertake a scoping review exploring the relationship between childhood obesity and salivary biomarkers to answer the following question: “Are salivary biomarkers trustful factors/indicators for childhood obesity?” The main search terms used were: “obesity and salivary biomarkers and children” (Pubmed, Scielo, Scopus, Embase databases: 1999–2025). Assessed articles were carefully classified according to a predetermined criterion (Newcastle–Ottawa Scale), and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were considered. Papers involving children >13 years, duplicates/triplicates, literature reviews, and non-related to the question addressed were excluded. More than 30 salivary biomarkers were assessed in the thirteen studies appraised. Three studies were rated as having a high level of evidence, two as moderate, and eight as having a low level. Fourteen biomarkers were found to be significantly increased in childhood obesity/overweight (p < 0.05): leptin, insulin, α-amylase, tumor necrosis factor α, interleukin 6, vascular endothelial growth factor-A, C-reactive protein, monocyte chemotactic protein-1, resistin, phosphate, nitric oxide, interleukin 1β, uric acid and fetuin-A; and three were found to be significantly decreased (p < 0.05): adiponectin, secretory immunoglobulin A, and interleukin-12p70. In conclusion, the present review supported the idea that saliva might be a promising diagnostic tool in early life and that it is a significant source of obesity biomarkers in children. Full article

Background/Objectives: Sepsis remains one of the most serious and possibly fatal complications encountered in intensive care units. Considering the frequent use of narcotic analgesics in this setting, we investigated whether the cardiovascular and peripheral and central inflammatory features of sepsis could be modified by morphine. Methods: Rats were instrumented with femoral and intracisternal (i.c.) indwelling catheters and sepsis was induced by cecal ligation and puncture (CLP). Results: The i.v. administration of morphine (3 and 10 mg/kg) significantly and dose-dependently aggravated septic manifestations of hypotension and impaired cardiac autonomic activity, as reflected by the reductions in indices of heart rate variability (HRV). Cardiac contractility (dP/dtmax) was also reduced by morphine in septic rats. The morphine effects were mostly eliminated following (i) blockade of μ-opioid receptors by i.v. naloxone and (ii) inhibition of central PI3K, MAPK-ERK, MAPK-JNK, NADPH oxidase (NADPHox), or Rho-kinase (ROCK) by i.c. wortmannin, PD98059, SP600125, diphenyleneiodonium, and fasudil, respectively. Further, these pharmacologic interventions significantly reduced the heightened protein expression of toll-like receptor 4 (TLR4) and monocyte chemoattractant protein-1 (MCP1) in brainstem rostral ventrolateral medullary (RVLM), but not cardiac, tissues of CLP/morphine-treated rats. Conclusions: Morphine worsens cardiovascular and autonomic disturbances caused by sepsis through a mechanism mediated via μ-opioid receptors and upregulated central inflammatory, chemotactic, and oxidative signals. Clinical studies are warranted to re-affirm the adverse cardiovascular interaction between opioids and the septic challenge. Full article

We evaluated inflammatory markers among 389 surgically confirmed endometriosis cases and 505 controls from the Women’s Health Study: From Adolescence to Adulthood (A2A) cohort. Participants reported dysmenorrhea, acyclic pelvic pain, dyspareunia, and pain with bowel movements. Using multiplex assays, we measured their levels of plasma interleukin (IL)-1β, -6, -8, -10, and -16, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1 and -4, thymus and activation-regulated chemokine (TARC), and interferon gamma-induced protein (IP)-10. For each symptom, we computed biomarker-level geometric means (GMs) with 95% confidence intervals (95% CI) using multivariate linear regression among the endometriosis cases and controls, with interactions with case/control status tested using Wald statistics. Among the controls, those with dyspareunia had lower levels of IL-8 (GM_present = 4.64 [95% CI = 4.41–4.89] pg/mL vs. GM_absent = 4.99 [95% CI = 4.82–5.17] pg/mL; p = 0.02), and the IL-8 levels were lower for controls reporting pain with bowel movements (GM_present = 4.66 [95% CI = 4.43–4.89] vs. GM_absent = 4.96 [95% CI = 4.82–5.11] pg/mL, p = 0.03). No significant associations between pelvic pain symptoms and inflammatory markers were observed among the endometriosis cases; however, the relationship between inflammatory marker levels and pain experience varied by analgesic use at blood draw. Dyspareunia and pain with bowel movements were associated with inflammatory markers among the controls, while the associations between pelvic pain symptoms and inflammatory markers among the endometriosis cases differed by analgesic use. Full article

Background: Monocyte chemotactic protein-1 (MCP-1) was implicated in the progression of atherosclerosis and is associated with elevated stroke risk. However, there is limited evidence regarding the MCP-1 role as an early biomarker for predicting the severity and outcomes of acute ischemic stroke (AIS). This prospective pilot case–control study aims to offer preliminary evidence into whether MCP-1 levels are elevated in AIS, whether they vary across different stroke subtypes, and their potential utility as a biomarker for assessing stroke severity and predicting outcomes. Methods: MCP-1 levels were quantified using ELISA in patients with AIS or transients ischemic attack (TIA) and healthy participants. Stroke severity was assessed with the NIHSS score and functional outcome with the mRS scale. Results: A total of 32 patients with AIS or TIA were compared to 13 healthy controls. MCP-1 levels were found to be 77% higher in stroke patients compared to healthy controls (p < 0.001). No significant differences in MCP-1 levels were observed between patients with AIS and those with TIA, nor among different stroke subtypes. A positive correlation was observed between MCP-1 levels and NIHSS changes from admission to discharge (b = 0.376, p < 0.05) and mRS scale at 6-month follow-up (b = 0.507, p < 0.05). Conclusions: This prospective pilot study provides preliminary evidence that MCP-1 levels are significantly elevated in AIS and are associated with NIHSS change during hospitalization and unfavorable outcome at 6-month follow-up. These findings indicate the potential of MCP-1 as an early biomarker for assessing disease severity and predicting outcomes in AIS. Full article

Background & Objectives: Targeted-release budesonide (TRB) is the first approved agent aimed at targeting the early pathogenetic cascade in IgA nephropathy (IgAN). Materials and Methods: This prospective study included Caucasian IgAN patients diagnosed within the last 5 years, who had started a 10-month TRB treatment and were followed in the outpatient clinic. All participants had been on the maximal supportive care dose for at least the previous 6 months. Kidney function and proteinuria levels were recorded at the start of TRB treatment (T0) and at 3, 6, and 10 months (T3, T6, and T10, respectively), while urinary monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9) and clusterin (CLU) levels were measured at T0 and T3. Results: In the cohort of all patients (mean age 53.24 ± 12.76 years, estimated glomerular filtration rate (eGFR 52.84 ± 25.93 mL/min/1.73 m², proteinuria 2.84 ± 1.26 g/24 h), significant correlations were observed at T0 between MMP-9 and MCP-1 (r = 0.74, p = 0.004), MMP-9 and uCLU (r = 0.77, p = 0.002), and MCP-1 and uCLU (r = 0.65, p = 0.01). At T3, a significant correlation between MMP-9 and urinary CLU (uCLU) persisted (r = 0.71, p = 0.03). Higher MCP-1 (r = −0.560, p = 0.046) and MMP-9 (r = −0.330, p = 0.012) levels at T0 were associated with reduced proteinuria. Conversely, increased clusterin at T3 (r = 0.599, p = 0.031) was associated with worsening proteinuria. Conclusions: The treatment response to TRB was heterogeneous, with recent diagnosis (RD) patients showing improved kidney function and proteinuria, while older diagnosis (OD) patients exhibited worsening biomarkers and declining kidney function. Therefore, early interventions are crucial in IgAN patients. Finally, the biomarkers studied can be used prognostically to monitor disease progression. Full article

The endothelial layer, formed by endothelial cells, performs crucial functions in maintaining homeostasis. The endothelial integrity and function might be compromised due to various causes, including infection by Toxoplasma gondii, leading to an endothelial dysfunction. Toxoplasma gondii is an Apicomplexa parasite that infects a broad range of animals, including humans. This parasite can invade all nucleated cells, as well as endothelial cells. The interaction between this protozoan and endothelial cells can be mediated by different molecules, such as extracellular vesicles (EVs), which may either favor or hinder the infectious process. To investigate this interaction, we evaluated the infection of T. gondii on human brain microvascular endothelial cells (HBMEC) and human umbilical vein endothelial cells (HUVEC), in addition to assessing transcriptional changes. We also featured the EVs secreted by T. gondii and by infected and non-infected HBMEC and HUVEC. Finally, we evaluated the infection of cells stimulated with EVs of parasitic or cellular origin. Our results demonstrated that HUVEC not only exhibit a higher infection rate than HBMEC but also display a more pro-inflammatory transcriptional profile, with increased expression of interleukin-6 (IL6), interleukin-8 (IL8), and monocyte chemotactic protein-1 (MCP1) following infection. Additionally, we observed few differences in the concentration, distribution, and morphology of EVs secreted by both cell types, although their properties in modulating infection varied significantly. When cells were EVs stimulated, EVs from T. gondii promoted an increase in the HBMEC infection, EVs from infected or uninfected HBMEC reduced the infection, whereas EVs from HUVEC had no effect on the infectious process. In conclusion, our data indicate that T. gondii infection induces distinct changes in different endothelial cell types, and EVs from these cells can contribute to the resolution of the infection. Full article

The systemic inflammatory response after cardiopulmonary bypass has been widely studied. However, there is a paucity of studies that focus on the local inflammatory changes that occur in the pericardial cavity. The purpose of this study is to assess the inflammatory mediators in the pericardial fluid of patients undergoing cardiac surgery. We conducted a prospective cohort study on patients undergoing aortic valve replacement. Pericardial fluid and peripheral venous blood samples were collected after the opening of the pericardium. Additional samples were obtained from peripheral blood and the pericardial fluid shed through mediastinal drains 24 and 48 h after surgery. Levels of interleukin 1α (IL-1α), interleukin 1β (IL-1β), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), 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 all 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 IL-6, IL-8, and MCP-1 were significantly increased at 24 and 48 h after surgery. No significant changes were observed in the serum levels of the remaining mediators. A significant increase of postoperative pericardial fluid levels of IL-1α, IL-1β, IL-6, IL-8, IL-10, IFN-γ, VEGF, MCP-1, VCAM-1, and P-selectin was observed at 24 and 48 h after surgery. There is a robust systemic and pericardial inflammatory response after cardiac surgery on cardiopulmonary bypass. However, postoperative pericardial inflammatory activity shows a distinct pattern and is more marked than at the systemic level. These findings suggest that there is a compartmentalization of the inflammatory response within the pericardial cavity after cardiac surgery. Full article

Background/Objectives: A novel patient group with chronic pulmonary fibrosis is emerging post COVID-19. To identify patients at risk of developing post-COVID-19 lung fibrosis, we here aimed to identify systemic proteins that overlap with fibrotic markers identified in patients with idiopathic pulmonary fibrosis (IPF) and may predict COVID-19-induced lung fibrosis. Methods: Ninety-two proteins were measured in plasma samples from hospitalized patients with moderate and severe COVID-19 in Sweden, before the introduction of the vaccination program, as well as from healthy individuals. These measurements were conducted using proximity extension assay (PEA) technology with a panel including inflammatory and remodeling proteins. Histopathological alterations were evaluated in explanted lung tissue. Results: Connecting to IPF pathology, several proteins including decorin (DCN), tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) and chemokine (C-X-C motif) ligand 13 (CXCL13) were elevated in COVID-19 patients compared to healthy subjects. Moreover, we found incrementing expression of monocyte chemotactic protein-3 (MCP-3) and hepatocyte growth factor (HGF) when comparing moderate to severe COVID-19. Conclusions: Both extracellular matrix- and inflammation-associated proteins were identified as overlapping with pulmonary fibrosis, where we found DCN, TNFRSF12A, CXCL13, CXCL9, MCP-3 and HGF to be of particular interest to follow up on for the prediction of disease severity. Full article

The root bark of Dictamus dasycarpus Turcz. has been traditionally used for the topical treatment of skin disorders like pruritus. This study was designed to investigate the inflammatory and skin barrier protective effects of D. dasycarpus in mice with calcipotriol (MC903)-induced atopic dermatitis (AD). Topical skin lesions on male Balb/c mice (8 weeks old) were treated topically with an ethanolic extract of D. dasycarpus (EEDD), and skin water content, water holding capacity (WHC), histopathological abnormalities, and inflammatory cytokine and chemokine levels were investigated. Topical application of EEDD effectively alleviated skin lesion severity, improved skin water content and WHC, and ameliorated histopathological abnormalities, including hyperkeratosis, blood vessel numbers near the epidermis, spongiotic changes, and immune cell infiltration in skin tissues. EEDD also suppressed inflammatory cytokines and chemokines, such as tumor necrosis factor (TNF)-α, thymic stromal lymphopoietin (TSLP), interleukin (IL)-1β, IL-4, IL-8, and monocyte chemotactic protein (MCP)-1. In RAW264.7 cells, EEDD reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) expression and suppressed the phosphorylations of extracellular signal-regulated kinase (ERK) and p38. These results suggest that the root bark of D. dasycarpus has therapeutic potential due to its anti-dermatitis and skin barrier protective effects in AD and that it could be used as an ingredient in skincare products. Full article

Tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) promote immune evasion, cancer cell proliferation, and metastasis. Ongoing research is focused on finding ways to prevent tumor growth by inhibiting TAM polarization, which has shown a correlation with unfavorable prognosis in clinical studies. Pancreatic adenocarcinoma up-regulated factor (PAUF) is a protein secreted from pancreatic cancer (PC) and acts as a TME modulator that affects the TME by acting on not only cancer cells but also stromal cells and immune cells. Tumor cells can evade the immune system by PAUF binding to Toll-like receptor (TLR) in monocytes, as this research shows. In this study, the examination centered around the recruitment of human monocytes by PAUF and the subsequent differentiation into macrophages. In an in vitro chemotaxis assay, PAUF induced chemotactic migration of TLR2-mediated monocytes. In addition, PAUF induced differentiation of monocytes into M2 macrophages, which was verified based on expressing surface markers and cytokines and morphological analysis. The inhibition of T cell proliferation and function was observed in differentiated M2 macrophages. To conclude, these findings indicate that PAUF functions as a promoter of cancer progression by regulating the recruitment and differentiation of macrophages within TMEs, ultimately causing immunosuppression. Full article

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. Full article

It is not clear whether immunoregulatory cytokines and cells are associated with Disease Activity Score 28 (DAS28) scores and ultrasound grades/scores. Here, we investigated the relationships between immunoregulatory cytokines or cells and different DAS28 scores or ultrasound grades/scores in patients with rheumatoid arthritis (RA). This study enrolled 50 RA patients (with 147 visits) who had remission/low/moderate DAS28-ESR scores (92% in remission and low disease activity) at baseline. Blood was collected and an ultrasound was performed three times in a year. Percentages of regulatory B cells and T regulatory type 1 cells and M2 macrophage numbers in the blood were examined. Plasma levels of 10 immunoregulatory cytokines IL-4, IL-5, IL-9, IL-10, IL-13, IL-27, IL-35, TGF-β1, sTNF-R1, and sTNF-R2 and monocyte chemotactic protein-1 (MCP-1) were assessed using ELISA assay. The correlations of cytokines and cells with different DAS28 scores and ultrasound grades were investigated, and cytokines and cells were compared between different categories of DAS28 scores and ultrasound grades. Plasma TGF-β1 levels were higher in the DAS28-ESR < 2.6 (remission) subgroup than in the DAS28-ESR ≥ 2.6 (nonremission) subgroup (p = 0.037). However, plasma TGF-β1 levels were higher in the high ultrasound grade subgroup than those in the low ultrasound grade subgroup (p = 0.007). The number of M2 macrophages was lower in the DAS28-MCP-1 < 2.2 subgroup than in the DAS28-MCP-1 ≥ 2.2 subgroup (p = 0.036). The levels of TGF-β1, sTNF-R2, IL-10, and IL-27 were higher in patients with high ultrasound grades than in those with low ultrasound grades. IL-27 was also higher in the nonremission DAS28-ESR subgroup than the remission one (p = 0.025). Moreover, sTNF-R1 levels in the 2011 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission subgroup were significantly lower than in the 2011 ACR/EULAR nonremission subgroup (p = 0.007). This trend was reflected in that lower sTNF-R1 levels correlated with low DAS28-MCP-1 scores (rho = 0.222, p = 0.007). We conclude that high plasma TGF-β1 levels indicate the DAS28-ESR remission (<2.6) subgroup and the high ultrasound grade subgroup. IL-27 probably connects the nonremission DAS28-ESR to high ultrasound grades. Low sTNF-R1 levels probably link low DAS28-MCP-1 scores with the 2011 ACR/EULAR remission subgroup. It suggests that incongruent immuno-inflammatory abnormalities exist between DAS28 scores and ultrasound grades, and are also dissimilar among various DAS28-formula categories. Therefore, this study may provide a basis for further research into individual cytokines and immunoregulatory cells behind each DAS28 formula and ultrasound grades/scores. Full article

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates advanced prognostic tools to anticipate disease progression and optimize patient outcomes. This study evaluates the predictive value and diagnostic potential of interleukins interleukin (IL) IL-10, IL-17A, IL1-β, IL-6, chemokine ligand (CXCL), and Monocyte Chemotactic Protein (MCP) for severe coronavirus disease 2019 (COVID-19) and COVID-19 mortality, aiming to correlate cytokine levels with disease severity. Conducted from January 2023 to January 2024, this prospective cohort study involved patients hospitalized with moderate and severe COVID-19 from Romania. This study analyzed statistically significant predictors of severe COVID-19 outcomes. IL-6 and MCP emerged as significant, with hazard ratios (HRs) of 2.35 (95% confidence interval (CI): 1.54–3.59, p = 0.014) and 2.05 (95% CI: 1.22–3.45, p = 0.007), respectively. Compound scores integrating multiple inflammatory markers also demonstrated predictive value; Compound Score 2 had an HR of 2.23 (95% CI: 1.35–3.68, p = 0.002), surpassing most single markers in association with severe disease. Notably, interleukins IL-10 and IL-1β did not show significant associations with disease severity. This study underscores the importance of IL-6 and MCP as robust predictors of severe COVID-19, substantiating their role in clinical assessments to foresee patient deterioration. The utility of compound scores in enhancing predictive accuracy suggests a composite approach may be more effective in clinical settings. Full article

Chronic inflammation is involved in the development of age-related diseases. Given its persistence, controlling chronic inflammation is essential for preventing age-related diseases. In this study, we investigated the effects of Enterococcus faecalis EC-12 (EC-12), which has immunomodulatory and antioxidant effects, on liver gene expression and aging phenomena in mice. Short-term EC-12 administration stimulated the expression of genes involved in lipid synthesis and metabolism in the liver. Furthermore, long-term EC-12 administration from 10 weeks to 1.5 years of age resulted in significant increases in blood interleukin (IL)-6 and IL-10 concentrations (both p < 0.05) and a significant decrease in the monocyte chemotactic protein-1 concentration (p < 0.05). These results indicated pathologic improvement, such as suppression of fat degeneration in the liver. These results suggest that continuous EC-12 intake from a young age can suppress liver function abnormalities, which is one of the aging phenomena in old age, and contribute to health in old age. Full article