RESUMEN
Cardiovascular disease is one of the leading causes of death worldwide. Evidence suggests that alterations in the gut microbiome could play a role in cardiovascular diseases, including heart failure. The purpose of this study was to evaluate the effect of synbiotics on serum paraoxonase 1(PON1), soluble CD163/soluble TNF-like weak inducer of apoptosis (sCD163/sTWEAK), and lipid profile, which are involved in heart failure in patients with chronic heart failure. In this triple-blind randomized clinical trial, 90 eligible patients were included in the study. They were randomly assigned to receive one capsule (500 mg) of synbiotics or a placebo daily for ten weeks. Serum PON1, sCD163/sTWEAK, and lipid profiles were measured at the beginning and end of the study. The data were analyzed by SPSS 24, and the p-value < 0.05 was considered statistically significant. Among 90 patients who met the inclusion criteria, 80 completed the study. The primary outcomes showed a small effect on sTWEAK, with an adjusted standard mean difference (SMD) of 0.2. However, no significant changes were observed in sCD163/sTWEAK (SMD: 0.16). Secondary outcomes indicated no changes in PON1, total cholesterol (TC), or LDL-C levels. However, there was an increase in HDL-C levels (adjusted SMD: 0.46, 95% CI: 0.02-0.91) and a decrease in TG and TC/HDL levels (adjusted SMD: - 0.5 and - 0.3, respectively) in the synbiotic group. A favorable effect of synbiotics on sTWEAK, HDL, TG, and TC/HDL of patients with heart failure was observed, but no statistically significant effect was found on sCD163/sTWEAK, PON1, LDL, and TC factors.
Asunto(s)
Arildialquilfosfatasa , Insuficiencia Cardíaca , Simbióticos , Humanos , Arildialquilfosfatasa/sangre , Masculino , Femenino , Simbióticos/administración & dosificación , Insuficiencia Cardíaca/sangre , Persona de Mediana Edad , Anciano , Receptores de Superficie Celular/sangre , Antígenos CD/sangre , Citocina TWEAK/sangre , Lipoproteínas/sangre , Enfermedad Crónica , Biomarcadores/sangre , Antígenos de Diferenciación MielomonocíticaRESUMEN
Background and Objectives: Inflammatory proteins and their prognostic value in patients with carotid artery stenosis (CAS) have not been adequately studied. Herein, we identified CAS-specific biomarkers from a large pool of inflammatory proteins and assessed the ability of these biomarkers to predict adverse events in individuals with CAS. Materials and Methods: Samples of blood were prospectively obtained from 336 individuals (290 with CAS and 46 without CAS). Plasma concentrations of 29 inflammatory proteins were determined at recruitment, and the patients were followed for 24 months. The outcome of interest was a major adverse cardiovascular event (MACE; composite of stroke, myocardial infarction, or death). The differences in plasma protein concentrations between patients with vs. without a 2-year MACE were determined using the independent t-test or Mann-Whitney U test to identify CAS-specific prognostic biomarkers. Kaplan-Meier and Cox proportional hazards analyses with adjustment for baseline demographic and clinical characteristics were performed to assess the prognostic value of differentially expressed inflammatory proteins in predicting a 2-year MACE in patients with CAS. Results: The mean age of the cohort was 68.8 (SD 10.2) years and 39% were female. The plasma concentrations of two inflammatory proteins were significantly higher in individuals with a 2-year MACE relative to those without a 2-year MACE: IL-6 (5.07 (SD 4.66) vs. 3.36 (SD 4.04) pg/mL, p = 0.03) and CD163 (233.825 (SD 230.306) vs. 159.673 (SD 175.669) pg/mL, p = 0.033). Over a follow-up period of 2 years, individuals with elevated levels of IL-6 were more likely to develop MACE (HR 1.269 (95% CI 1.122-1.639), p = 0.042). Similarly, over a 2-year period, patients with high levels of CD163 were more likely to develop MACE (HR 1.413 (95% CI 1.022-1.954), p = 0.036). Conclusions: The plasma levels of inflammatory proteins IL-6 and CD163 are independently associated with adverse outcomes in individuals with CAS. These CAS-specific prognostic biomarkers may assist in the risk stratification of patients at an elevated risk of a MACE and subsequently guide further vascular evaluation, specialist referrals, and aggressive medical/surgical management, thereby improving outcomes for patients with CAS.
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Biomarcadores , Estenosis Carotídea , Humanos , Femenino , Estenosis Carotídea/sangre , Estenosis Carotídea/complicaciones , Masculino , Biomarcadores/sangre , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Inflamación/sangre , Inflamación/complicaciones , Receptores de Superficie Celular/sangre , Pronóstico , Interleucina-6/sangre , Modelos de Riesgos Proporcionales , Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Estimación de Kaplan-Meier , Infarto del Miocardio/sangre , Infarto del Miocardio/complicaciones , Enfermedades Cardiovasculares/sangre , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/etiologíaRESUMEN
Soluble CD163 (sCD163) is a selective marker of macrophages whose circulating levels have been found to be induced in patients with active inflammatory bowel disease (IBD). Urinary proteins are emerging as non-invasive diagnostic biomarkers, and here, sCD163 levels were measured in the urine of 18 controls and 63 patients with IBD by enzyme-linked immunosorbent assay. Urinary sCD163 levels did, however, not differentiate IBD patients from controls. Analysis of sCD163 in the serum of 51 of these patients did not show higher levels in IBD. Primary sclerosing cholangitis (PSC) is often associated with IBD, and sCD163 was higher in the urine of the 21 patients and in the serum of the 13 patients with PSC compared to patients with IBD. Of clinical relevance, urinary sCD163 levels were higher in PSC patients compared to those with other chronic liver diseases (n = 16), while serum sCD163 levels were comparable between the two groups. Serum sCD163 of IBD and PSC patients positively correlated with serum C-reactive protein. Serum creatinine and glomerular filtration rate, surrogate markers for renal function, did not significantly correlate with urinary or serum sCD163 levels in IBD or PSC patients. Moreover, urinary sCD163 was not related to fecal calprotectin levels whereas serum sCD163 of IBD patients showed a positive trend. PSC associated with IBD and PSC without underlying IBD had similar levels of urinary sCD163 while serum sCD163 tended to be higher in the latter group. In PSC patients, urinary sCD163 did not correlate with serum aminotransferase levels, gamma glutamyl transferase, alkaline phosphatase, bilirubin or the Model for End Stage Liver Disease score. Ursodeoxycholic acid was prescribed to our PSC patients and fecal levels of ursodeoxycholic acid and its conjugated forms were increased in PSC compared to IBD patients. Otherwise, fecal bile acid levels of IBD and PSC patients were almost identical, and were not correlated with urinary and serum sCD163 in PSC. In summary, our study identified urinary sCD163 as a potential biomarker for PSC.
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Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Biomarcadores , Colangitis Esclerosante , Enfermedades Inflamatorias del Intestino , Receptores de Superficie Celular , Humanos , Antígenos de Diferenciación Mielomonocítica/sangre , Antígenos de Diferenciación Mielomonocítica/orina , Colangitis Esclerosante/orina , Colangitis Esclerosante/sangre , Antígenos CD/sangre , Antígenos CD/orina , Receptores de Superficie Celular/sangre , Biomarcadores/orina , Biomarcadores/sangre , Masculino , Femenino , Persona de Mediana Edad , Adulto , Enfermedades Inflamatorias del Intestino/orina , Enfermedades Inflamatorias del Intestino/sangre , Anciano , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Complejo de Antígeno L1 de Leucocito/orina , Complejo de Antígeno L1 de Leucocito/sangre , Complejo de Antígeno L1 de Leucocito/análisisRESUMEN
OBJECTIVES: Myeloid cell-derived factors contribute to the immunopathology of endometriosis. Soluble CD14 (sCD14), CD163 (sCD163), and MIF serve as in vivo markers of myeloid function. However, these soluble molecules are largely unexplored in women with endometriosis-related infertility cases. We investigated three soluble markers, namely sCD14, sCD163, and MIF, in cases of infertility associated with endometriosis and correlated its level to the stage of endometriosis. DESIGN: Eighty-seven women newly diagnosed with endometriosis or other benign gynecologic control cases linked to infertility were prospectively recruited and underwent diagnostic laparoscopy. PARTICIPANTS: Forty-four patients with endometriosis were included in this study, comprising 19 patients with early-endometriosis (stages I and II) and 25 late-endometriosis (stages III and IV) based on the revised American Society for Reproductive Medicine (rASRM) classification. The remaining 43 patients constituted a control group with infertility due to other causes. METHODS: The levels of sCD14, sCD163, and MIF in serum and peritoneal fluid were assessed using ELISA. RESULTS: Endometriosis women exhibited significantly higher serum levels of sCD163 and MIF levels compared to the control group. Both sCD163 and MIF levels displayed a positive correlation with the rASRM adhesion score. Moreover, the MIF level in serum had a positive correlation with the rASRM endometriosis score. In receiver operating characteristic analysis, serum sCD163 and MIF could significantly discriminate endometriosis and non-endometriosis in infertility cases. LIMITATIONS: Some limitations of the current study deserve to be underlined. First, the sensitive ELISA method was the sole-validated tool for detecting the markers in patient samples. Second, healthy or fertile women were not involved as the control group. CONCLUSIONS: The elevated systemic levels of sCD163 and MIF correlated with the severity of endometriosis. These soluble molecules have a potential diagnostic capacity as a non-invasive biomarker. Furthermore, our data warrants future studies on the underlying mechanism of sCD163 and MIF in endometriosis-related infertility.
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Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Biomarcadores , Endometriosis , Infertilidad Femenina , Receptores de Lipopolisacáridos , Factores Inhibidores de la Migración de Macrófagos , Receptores de Superficie Celular , Humanos , Femenino , Endometriosis/sangre , Endometriosis/complicaciones , Adulto , Antígenos CD/sangre , Receptores de Superficie Celular/sangre , Factores Inhibidores de la Migración de Macrófagos/sangre , Infertilidad Femenina/sangre , Infertilidad Femenina/etiología , Antígenos de Diferenciación Mielomonocítica/sangre , Biomarcadores/sangre , Receptores de Lipopolisacáridos/sangre , Oxidorreductasas Intramoleculares/sangre , Estudios de Casos y Controles , Estudios Prospectivos , Líquido Ascítico/química , Líquido Ascítico/metabolismoRESUMEN
BACKGROUND AND AIMS: Acute liver failure is a multisystem disorder with a high mortality and frequent need for emergency liver transplantation. Following massive innate immune system activation, soluble markers of macrophage activation are released during liver damage and their association with disease severity and prognosis requires exploration. METHODS: Patients ALF from the United States Acute Liver Failure Study Group (USALFSG, n = 224) and King's College Hospital (n = 40) together with healthy controls (HC, n = 50) were recruited. Serum from early (Days 1-3) and late (>Day 3) time points were analysed for MAMs by enzyme-linked immunosorbent assay correlated to markers of illness severity and 21-day spontaneous survival. Surface expression phenotyping was performed via Flow Cytometry on CD14+ monocytes. RESULTS: All MAMs serum concentrations were significantly higher in ALF compared to controls (p < .0001). sCD206 concentration was higher in early and late stages of the disease in patients with bacteraemia (p = .002) and infection in general (p = .006). In MELD-adjusted multivariate modelling, sCD206 and sCD163 were independently associated with mortality. CD14+ monocyte expression of CD206 (p < .001) was higher in patients with ALF compared with controls and correlated with SOFA score (p = .018). sCD206 was independently validated as a predictor of infection in an external cohort. CONCLUSIONS: sCD206 is increased in serum of ALF patients with infections and poor outcome and is upregulated on CD14+ monocytes. Later measurements of sCD163 and sCD206 during the evolution of ALF have potential as mechanistic predictors of mortality. sCD206 should be explored as a biomarker of sepsis and mortality in ALF.
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Antígenos de Diferenciación Mielomonocítica , Biomarcadores , Fallo Hepático Agudo , Activación de Macrófagos , Receptores de Superficie Celular , Humanos , Fallo Hepático Agudo/mortalidad , Fallo Hepático Agudo/sangre , Masculino , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , Adulto , Receptores de Superficie Celular/sangre , Estudios de Casos y Controles , Antígenos de Diferenciación Mielomonocítica/sangre , Antígenos CD/sangre , Índice de Severidad de la Enfermedad , Receptores de Lipopolisacáridos/sangre , Pronóstico , Lectinas Tipo C/sangre , Monocitos , Receptor de Manosa , Ensayo de Inmunoadsorción Enzimática , Lectinas de Unión a Manosa/sangre , Estados Unidos/epidemiología , Análisis Multivariante , Citometría de Flujo , AncianoRESUMEN
BACKGROUND: Kawasaki disease (KD) is a pediatric systemic vasculitis characterized by endothelial cell dysfunction. Semaphorin 7A (Sema7A) has been reported to regulate endothelial phenotypes associated with cardiovascular diseases, while its role in KD remains unknown. This study aims to investigate the effect of Sema7A on endothelial permeability and inflammatory response in KD conditions. METHODS: Blood samples were collected from 68 KD patients and 25 healthy children (HC). The levels of Sema7A and A Disintegrin and Metalloprotease 17 (ADAM17) in serum were measured by enzyme-linked immunosorbent assay (ELISA), and Sema7A expression in blood cells was analyzed by flow cytometry. Ex vivo monocytes were used for Sema7A shedding assays. In vitro human coronary artery endothelial cells (HCAECs) were cultured in KD sera and stimulated with Sema7A, and TNF-α, IL-1ß, IL-6, and IL-18 of HCAECs were measured by ELISA and qRT-PCR. HCAECs monolayer permeability was measured by FITC-dextran. RESULTS: The serum level of Sema7A was significantly higher in KD patients than in HC and correlated with disease severity. Monocytes were identified as one of the source of elevated serum Sema7A, which implicates a process of ADAM17-dependent shedding. Sera from KD patients induced upregulation of plexin C1 and integrin ß1 in HCAECs compared to sera from HC. Sema7A mediated the proinflammatory cytokine production of HCAECs in an integrin ß1-dependent manner, while both plexin C1 and integrin ß1 contributed to Sema7A-induced HCAEC hyperpermeability. CONCLUSIONS: Sema7A is involved in the progression of KD vasculitis by promoting endothelial permeability and inflammation through a plexin C1 and integrin ß1-dependent pathway. Sema7A may serve as a potential biomarker and therapeutic target in the prognosis and treatment of KD.
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Antígenos CD , Integrina beta1 , Síndrome Mucocutáneo Linfonodular , Receptores de Superficie Celular , Semaforinas , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Proteína ADAM17/metabolismo , Antígenos CD/metabolismo , Permeabilidad Capilar , Estudios de Casos y Controles , Células Cultivadas , Células Endoteliales/metabolismo , Endotelio Vascular/metabolismo , Proteínas Ligadas a GPI , Inflamación/metabolismo , Integrina beta1/metabolismo , Monocitos/metabolismo , Síndrome Mucocutáneo Linfonodular/metabolismo , Síndrome Mucocutáneo Linfonodular/sangre , Proteínas del Tejido Nervioso/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/sangre , Semaforinas/metabolismo , Semaforinas/sangreRESUMEN
BACKGROUND: The GLP-1 receptor agonist liraglutide is used to treat hyperglycemia in type 2 diabetes but is also known to induce weight loss, preserve the beta cell and reduce cardiovascular risk. The mechanisms underlying these effects are however still not completely known. Herein we explore the effect of liraglutide on markers of immune cell activity in a population of obese individuals with prediabetes or newly diagnosed type 2 diabetes mellitus. METHOD: Plasma levels of the monocyte/macrophage markers, soluble (s)CD163 and sCD14, the neutrophil markers myeloperoxidase (MPO) and neutrophil gelatinase-associated lipocalin (NGAL),the T-cell markers sCD25 and T-cell immunoglobulin mucin domain-3 (sTIM-3) and the inflammatory marker TNF superfamily (TNFSF) member 14 (LIGHT/TNFSF14) were measured by enzyme-linked immunosorbent assays in obese individuals with prediabetes or diabetes diagnosed within the last 12 months, prior to and after comparable weight loss achieved with lifestyle changes (n = 20) or liraglutide treatment (n = 20), and in healthy subjects (n = 13). RESULTS: At baseline, plasma levels of the macrophage marker sCD163, and the inflammatory marker LIGHT were higher in cases as compared to controls. Plasma levels of sCD14, NGAL, sTIM-3 and sCD25 did not differ at baseline between patients and controls. After weight reduction following lifestyle intervention or liraglutide treatment, sCD163 decreased significantly in the liraglutide group vs. lifestyle (between-group difference p = 0.023, adjusted for visceral adipose tissue and triglycerides basal values). MPO and LIGHT decreased significantly only in the liraglutide group (between group difference not significant). Plasma levels of MPO and in particular sCD163 correlated with markers of metabolic dysfunction and inflammation. After weight loss, only sCD163 showed a trend for decreased levels during OGTT, both in the whole cohort as in those of liraglutide vs lifestyle group. CONCLUSION: Weight loss following treatment with liraglutide was associated with reduced circulating levels of sCD163 when compared to the same extent of weight loss after lifestyle changes. This might contribute to reduced cardiometabolic risk in individuals receiving treatment with liraglutide.
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Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Biomarcadores , Diabetes Mellitus Tipo 2 , Incretinas , Liraglutida , Obesidad , Estado Prediabético , Receptores de Superficie Celular , Conducta de Reducción del Riesgo , Pérdida de Peso , Humanos , Liraglutida/uso terapéutico , Liraglutida/efectos adversos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/terapia , Pérdida de Peso/efectos de los fármacos , Masculino , Persona de Mediana Edad , Femenino , Obesidad/diagnóstico , Obesidad/sangre , Obesidad/terapia , Biomarcadores/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Estado Prediabético/sangre , Estado Prediabético/diagnóstico , Estado Prediabético/terapia , Estado Prediabético/tratamiento farmacológico , Receptores de Superficie Celular/sangre , Resultado del Tratamiento , Antígenos CD/sangre , Incretinas/uso terapéutico , Incretinas/efectos adversos , Incretinas/sangre , Adulto , Estudios de Casos y Controles , Factores de Tiempo , Regulación hacia Abajo , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , AncianoRESUMEN
Chronic HCV infection induces interferon and dysregulates immune responses through inflammation and chronic antigenic stimulation. Antiviral drugs can cure HCV, providing a unique opportunity to examine the immunological restoration that does and does not occur when a chronic viral infection is eradicated. We quantified blood cytokines levels and used mass cytometry to immunophenotype peripheral blood mononuclear cells before and after HCV cure in 2 groups of patients and controls. At baseline, serum interferon α and soluble CD163 (a macrophage product) were elevated in both liver transplant and nonliver transplant patients compared to controls; the frequencies of several peripheral blood mononuclear cell populations differed from controls; and programmed death protein 1-positivity was increased in nearly all T cell subsets. Many abnormalities persisted after HCV cure, including elevated programmed death protein 1 expression on CD4 naïve and central memory T cells, elevated soluble CD163, and expansion of the plasmablast/plasma cell compartment. Several myeloid-lineage subsets, including Ag-presenting dendritic cells, remained dysregulated. In mechanistic studies, interferon α treatment increased programmed death protein 1 on human T cells and increased T cell receptor signaling. The data identify immunological abnormalities that persist after curative HCV treatment. Before cure, high levels of interferon α may stimulate programmed death protein 1 expression on human T cells, causing persistent functional changes.
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Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Antivirales , Hepatitis C Crónica , Interferón-alfa , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Masculino , Antivirales/uso terapéutico , Persona de Mediana Edad , Femenino , Antígenos CD/inmunología , Antígenos CD/sangre , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/sangre , Antígenos de Diferenciación Mielomonocítica/inmunología , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/sangre , Hepatitis C Crónica/cirugía , Interferón-alfa/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Receptores de Superficie Celular/sangre , Receptores de Superficie Celular/inmunología , Adulto , Estudios de Casos y Controles , Anciano , Hepacivirus/inmunología , Hepacivirus/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Citocinas/sangre , Inmunofenotipificación , Resultado del TratamientoRESUMEN
BACKGROUND: Patients with anti-tRNA autoantibodies are characterized by arthritis, mechanic´s hands, fever, Raynaud´s phenomenon, and interstitial lung disease (ILD), in at least two clinical scenarios: the antisynthetase syndrome (ASSD) and interstitial pneumonia with autoimmune features (IPAF). The anti-tRNA-ILD treatment is centered on the administration of corticosteroids and a wide variety of immunosuppressive drugs; however, the effectiveness of the treatment depends on factors not fully understood. This research work aimed to quantify the serum levels of two molecules related to pulmonary fibrosis and explore their relationship with the progression of ILD associated with ASSD METHODOLOGY: Serum levels of sCD163 and TGF-ß1 from baseline and after six months of treatment of ILD patients' positives to anti-tRNA were included in the current study. At six months, patients were classified as with or without ILD progression RESULTS: Forty patients were included (anti-Jo1, anti-PL7, anti-PL12, and anti-Ej). Five patients (12.5%) had ILD progression and were characterized by higher levels of sCD163 at baseline. Baseline sCD163 serum levels showed good discriminatory capacity in patients with ILD progression. On the other hand, at follow-up, serum TGF-ß1 levels significantly increased in both patients' groups, with and without progression CONCLUSION: Basal levels of sCD163 were higher in patients who later developed ILD progression and kinetics of both molecules suggests the participation of M2 macrophages in the development of ILD.
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Aminoacil-ARNt Sintetasas , Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Enfermedades Pulmonares Intersticiales , Receptores de Superficie Celular/sangre , Autoanticuerpos , Progresión de la Enfermedad , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Miositis , ARN , Factor de Crecimiento Transformador beta1RESUMEN
BACKGROUND: To date, no study has investigated the effects of probiotic yogurt as a functional food in patients with chronic heart failure (CHF). Therefore, the aim of this study was to compare the impact of probiotic yogurt versus ordinary yogurt on inflammatory, endothelial, lipid and renal indices in CHF patients. In this randomized, triple-blind clinical trial, 90 patients with CHF were randomly allocated into two groups to take either probiotic or ordinary yogurt for 10 weeks. Serum levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), soluble cluster of differentiation 163 (sCD163), asymmetric dimethylarginine (ADMA), and lecithin cholesterol acyltransferase (LCAT) were measured by using ELISA kits, and blood urea nitrogen (BUN) was measured by calorimetry method at baseline and at the end of trial. The P-value <0.05 was defined as statistically significant. RESULTS: Seventy-eight patients completed the study. At the end of the intervention, the levels of sTWEAK in both groups increased significantly, and this increase was greater in the probiotic yogurt group [691.84 (335.60, 866.95)] compared to control group [581.96 (444.99, 929.40)], and the difference between the groups was statistically significant after adjusting for confounders (P-value: 0.257, adjusted P-value: 0.038). However, no significant differences were found between the groups in the cases of other study indices. CONCLUSION: Probiotic yogurt may be useful for improving the inflammatory status in patients with CHF through increasing sTWEAK levels, however, further studies are needed in this area. © 2022 Society of Chemical Industry.
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Insuficiencia Cardíaca , Probióticos , Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Arginina/análogos & derivados , Nitrógeno de la Urea Sanguínea , Citocina TWEAK/sangre , Insuficiencia Cardíaca/terapia , Humanos , Fosfatidilcolina-Esterol O-Aciltransferasa , Receptores de Superficie Celular/sangre , Factor de Necrosis Tumoral alfa , YogurRESUMEN
BACKGROUND: Serum indicators AFP, CA50, CA125, CA153, CA19-9, CEA, f-PSA, SCC-Ag have been confirmed as tumor markers (TMs). We conducted a genome-wide association study on 8 tumor markers of our 427 Han population in southern China, in order to identify genetic loci that are significantly associated with the level of 8 tumor markers. METHODS: We use Gene Titan multi-channel instrument and Axiom Analysis Suite 6.0 software for genotyping. We used IMPUTE2 software for imputation, and 1000 Genomes Project (Phase 3) was used as haplotype reference. After necessary quality control and statistical analysis, genetic loci genome-wide associated with TMs (p < 5E-8) will be identified. Finally, we selected Top SNPs (p < 5E-7) from the GWAS results for replication test. We used SPSS software to draw the distribution box plots of serum TMs under different genotypes of significant loci. RESULTS: The results showed that there were only MUC1 (mucin 1)-rs4072037 significantly genome-wide associated with CA153 (p = 1.28E-18). However, we found that a total of 30 genetic loci have a suggestively significant genome-wide association with the level of 8 serum tumor markers (p < 5E-6). Then 3 Top SNPs (p < 5E-7) were selected for replication verification. The results showed that MUC1-rs4072037 was still significantly associated with CA153 in another population (p = 3.73E-08). Comparing with the TT genotype of rs4072037, the CA153 level was higher under CC or CT genotype of rs4072037. CONCLUSION: MUC1-rs4072037 is significantly genome-wide associated with CA153 level. There are 30 genetic loci suggestively genome-wide associated with level of tumor markers among the Han population from Southern China.
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Pueblo Asiatico/genética , Biomarcadores de Tumor/sangre , Etnicidad/genética , Predisposición Genética a la Enfermedad/etnología , Predisposición Genética a la Enfermedad/genética , Adulto , Antígenos de Neoplasias/sangre , Antígenos de Carbohidratos Asociados a Tumores/sangre , Antígeno Ca-125/sangre , China , Femenino , Sitios Genéticos/genética , Estudio de Asociación del Genoma Completo , Genotipo , Técnicas de Genotipaje , Humanos , Calicreínas/sangre , Masculino , Proteínas de la Membrana/sangre , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Antígeno Prostático Específico/sangre , Receptores de Superficie Celular/sangre , Serpinas/sangre , alfa-Fetoproteínas/genéticaRESUMEN
BACKGROUND: Cytokine measurements to support clinical laboratory and research investigations have become increasingly common in pediatrics. However, there is a paucity of accurate pediatric reference intervals (RIs) essential to the interpretation of cytokine results. To address this gap, here, we establish age- and sex-specific pediatric reference values for clinically relevant inflammatory markers including CD163, and the cytokines IL-1ß, IL-6, IL-10, IL-18, TNF-α, IFN-γ, and CXCL-9. METHODS: Healthy children and adolescents (n = 311, 1-19 years) were recruited as part of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) study. Multi-analyte measurements in plasma and analytical performance verification were conducted on the ProteinSimple® Ella™ automated immunoassay platform (Bio-Techne, MN, USA). Age- and sex-specific RIs were calculated based on Clinical and Laboratory Standards Institute guidelines. Additionally, 75th and 95th percentile cut-offs were determined. RESULTS: Three types of reference value distributions were observed: (a) consistent levels throughout age and sex: IL-6, and IFN-γ, (b) gradual decline in concentration with age: CD163, TNF-α, CXCL-9, and IL-10, (c) significantly higher concentrations during ages 4-14 years than earlier and later ages: IL-1ß and IL-18. Reference values for CXCL-9, IL-10, and TNF-α under 8 years of age differed significantly from older children. CD163, IL-18 and IL-1ß required three age partitions. CD163 demonstrated significant sex differences in ages 8-13 years. CONCLUSION: The circulating profile of cytokines in children is complex and can vary by age and sex. This necessitates careful interpretation of test results based on age and/or sex specific RIs facilitating more accurate clinical decision making.
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Envejecimiento/sangre , Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Citocinas/sangre , Receptores de Superficie Celular/sangre , Caracteres Sexuales , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Valores de ReferenciaRESUMEN
The (pro)renin receptor [(P)RR)] is a multifunctional protein that is cleaved to generate the soluble (P)RR [s(P)RR], reflecting the status of the tissue renin-angiotensin system and/or activity of the (P)RR. The serum s(P)RR level is associated with arteriosclerosis, independent of other risk factors, in patients undergoing hemodialysis (HD). This study was conducted to investigate whether the s(P)RR level was associated with new-onset cardiovascular events or malignant diseases and poor prognosis in patients undergoing HD. Overall, 258 patients [70 (61-76) years, 146 males] undergoing maintenance HD were prospectively followed up for 60 months. We investigated the relationships between s(P)RR levels and new-onset cardiovascular events/ malignant diseases and mortality during the follow-up period using Cox proportional hazard analyses. The cumulative incidence of new-onset cardiovascular events (P = 0.009) and deaths (P < 0.001), but not of malignant diseases, was significantly greater in patients with higher serum s(P)RR level (≥ 29.8 ng/ml) than in those with lower s(P)RR level (< 29.8 ng/ml). A high serum s(P)RR level was independently correlated with cardiovascular mortality (95% CI 1.001-1.083, P = 0.046). The serum s(P)RR level was associated with cardiovascular events and mortality, thus qualifying as a biomarker for identifying patients requiring intensive care.
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Precursores de Proteínas/sangre , Receptores de Superficie Celular/sangre , Diálisis Renal , ATPasas de Translocación de Protón Vacuolares/sangre , Anciano , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Pronóstico , Factores de RiesgoRESUMEN
Intravascular hemolysis (IH) contributes to the development of endothelial dysfunction (ED) in sickle cell anemia (SCA), and the effects of hydroxyurea (HU, the only approved drug that decreases the frequency and severity of vaso-oclussive crises) on IH and ED in SCA remain unclear. We evaluated and compared the markers of IH among steady-state adult Brazilians with SCA and HbAA individuals. Overall, this cross-sectional study enrolled 30 SCA patients not receiving HU therapy (HbSS), 25 SCA patients receiving HU therapy (HbSS_HU), and 32 HbAA volunteers (HbAA). The IH markers evaluated were serum Lactate Dehydrogenase (LDH), total heme, plasma hemoglobin (pHb), and soluble CD163 (sCD163). The ED markers analyzed were plasma von Willebrand factor (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo) levels, antigen of VWF-cleaving protease (ADAMTS13:Ag), thrombospondin-1, endothelin-1 levels, and ADAMTS13 Activity (ADAMTS13:Act). The levels of VWF:Ag, VWF:RCo, total heme, thrombospondin-1, and endothelin-1 were significantly higher in SCA patients (HbSS and HbSS_HU) compared to HbAA individuals. Also, pHb, LDH, and thrombospondin-1 levels were significantly higher in the HbSS group than in the HbSS_HU group. Contrarily, the levels of sCD163, ADAMTS13:Ag, and ADAMTS13:Act were significantly lower in both groups of SCA patients than HbAA controls, and ADAMTS13:Act levels were significantly lower in HbSS compared to HbSS_HU patients. The higher ADAMTS13 activity levels in those on HU therapy may be attributed to lower pHb and thrombospondin-1 levels as previously shown by in vitro studies that thrombospondin-1 and pHb are bound to VWF. Thus, VWF is restrained from ADAMTS13 activity and cleavage.
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Anemia de Células Falciformes/tratamiento farmacológico , Endotelio Vascular/fisiopatología , Hemólisis/efectos de los fármacos , Hidroxiurea/uso terapéutico , Proteína ADAMTS13/sangre , Adolescente , Adulto , Anemia de Células Falciformes/sangre , Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Biomarcadores , Estudios Transversales , Endotelio Vascular/efectos de los fármacos , Femenino , Hemo/análisis , Hemoglobinas/análisis , Humanos , Hidroxiurea/farmacología , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Prohibitinas , Receptores de Superficie Celular/sangre , Trombospondina 1/sangre , Adulto Joven , Factor de von Willebrand/análisisRESUMEN
In ischemic stroke patients, a higher monocyte count is associated with disease severity and worse prognosis. The complex correlation between subset phenotypes and functions underscores the importance of clarifying the role of monocyte subpopulations. We examined the subtype-specific distribution of the CD163+ and CD80+ circulating monocytes and evaluated their association with the inflammatory status in 26 ischemic stroke patients and 16 healthy controls. An increased percentage of CD163+/CD16+ and CD163+/CD14++ events occurred 24 and 48 h after a stroke compared to the controls. CD163+ expression was more pronounced in CD16+ non-classical and intermediate monocytes, as compared to CD14+ classical subtype, 24 h after stroke. Conversely, the percentage of CD80+/CD16+ events was unaffected in patients; meanwhile, the percentage of CD80+/CD14+ events significantly increased only 24 h after stroke. Interleukin (IL)-1beta, TNF-alpha, and IL-4 mRNA levels were higher, while IL-10 mRNA levels were reduced in total monocytes from patients versus controls, at either 24 h or 48 h after stroke. The percentage of CD163+/CD16+ events 24 h after stroke was positively associated with NIHSS score and mRS at admission, suggesting that stroke severity and disability are relevant triggers for CD163+ expression in circulating CD16+ monocytes.
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Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Biomarcadores/sangre , Accidente Cerebrovascular Isquémico/sangre , Monocitos/metabolismo , Receptores de Superficie Celular/sangre , Anciano , Anciano de 80 o más Años , Antígeno B7-1/metabolismo , Biomarcadores/metabolismo , Estudios de Casos y Controles , Estudios Transversales , Citocinas/genética , Femenino , Proteínas Ligadas a GPI/metabolismo , Humanos , Accidente Cerebrovascular Isquémico/etiología , Masculino , Persona de Mediana Edad , Receptores de IgG/metabolismo , Índice de Severidad de la EnfermedadRESUMEN
Venous thromboembolism is the third common cardiovascular disease and is composed of two entities, deep vein thrombosis (DVT) and its potential fatal form, pulmonary embolism (PE). While PE is observed in ~ 40% of patients with documented DVT, there is limited biomarkers that can help identifying patients at high PE risk. To fill this need, we implemented a two hidden-layers artificial neural networks (ANN) on 376 antibodies and 19 biological traits measured in the plasma of 1388 DVT patients, with or without PE, of the MARTHA study. We used the LIME algorithm to obtain a linear approximate of the resulting ANN prediction model. As MARTHA patients were typed for genotyping DNA arrays, a genome wide association study (GWAS) was conducted on the LIME estimate. Detected single nucleotide polymorphisms (SNPs) were tested for association with PE risk in MARTHA. Main findings were replicated in the EOVT study composed of 143 PE patients and 196 DVT only patients. The derived ANN model for PE achieved an accuracy of 0.89 and 0.79 in our training and testing sets, respectively. A GWAS on the LIME approximate identified a strong statistical association peak (rs1424597: p = 5.3 × 10-7) at the PLXNA4 locus. Homozygote carriers for the rs1424597-A allele were then more frequently observed in PE than in DVT patients from the MARTHA (2% vs. 0.4%, p = 0.005) and the EOVT (3% vs. 0%, p = 0.013) studies. In a sample of 112 COVID-19 patients known to have endotheliopathy leading to acute lung injury and an increased risk of PE, decreased PLXNA4 levels were associated (p = 0.025) with worsened respiratory function. Using an original integrated proteomics and genetics strategy, we identified PLXNA4 as a new susceptibility gene for PE whose exact role now needs to be further elucidated.
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Predisposición Genética a la Enfermedad/genética , Redes Neurales de la Computación , Proteómica , Embolia Pulmonar/sangre , Embolia Pulmonar/genética , Receptores de Superficie Celular/sangre , Receptores de Superficie Celular/genética , Adulto , COVID-19/complicaciones , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple , Embolia Pulmonar/complicaciones , Embolia Pulmonar/metabolismoRESUMEN
OBJECTIVE: The proprotein convertase furin is known to be involved in the processing of pro-B-type natriuretic peptide (proBNP) and prorenin receptor (PRR), suggesting that it has a potential function in blood pressure regulation. We investigated the role of furin in the etiology of pre-eclampsia and its related disorder, unexplained fetal growth restriction (FGR) without hypertension. METHODS: We evaluated serum and placental furin levels in pre-eclampsia, FGR and uncomplicated pregnancy. Additionally, we investigated the correlation between the serum furin levels and products of furin enzymatic activity or clinical parameters. RESULTS: We demonstrated that the maternal circulation in cases of pre-eclampsia and FGR had lower levels of soluble furin than uncomplicated pregnancies. Both NT-proBNP and soluble PRR were elevated in pre-eclampsia, whereas only soluble PRR was at higher levels in unexplained FGR. Linear regression analysis revealed a negative correlation between the serum furin level and that of NT-proBNP or soluble PRR. While we observed that the serum furin or soluble PRR level correlated with blood pressure, a stronger correlation was observed with birth and placental weights. Further to this, the FURIN mRNA levels were significantly reduced in placental pre-eclamptic placentas as well as in FGR cases. CONCLUSION: These data suggest the possibility that reduced levels of furin may be the result of a negative feedback from the activation of the renin-angiotensin pathway that leads to feto-placental dysfunction with or without maternal hypertension. This may represent an etiologic pathway of pre-eclampsia and unexplained FGR.
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Retardo del Crecimiento Fetal/sangre , Furina/análisis , Preeclampsia/sangre , Receptores de Superficie Celular/análisis , Adulto , Biomarcadores/análisis , Biomarcadores/sangre , Femenino , Retardo del Crecimiento Fetal/diagnóstico , Retardo del Crecimiento Fetal/epidemiología , Furina/sangre , Humanos , Japón/epidemiología , Preeclampsia/diagnóstico , Preeclampsia/epidemiología , Embarazo , Receptores de Superficie Celular/sangre , Receptor de ProreninaRESUMEN
Circulating monocytes have pathogenic relevance in idiopathic pulmonary fibrosis (IPF). Here, we determined whether the cell surface levels of two markers, pro-inflammatory-related S100A9 and anti-inflammatory-related CD163, expressed on CD14strongCD16- classical monocytes by flow cytometry could discriminate IPF from idiopathic nonspecific interstitial pneumonia (iNSIP). Twenty-five patients with IPF, 25 with iNSIP, and 20 healthy volunteers were prospectively enrolled in this study. The S100A9+CD163- cell percentages in classical monocytes showed a pronounced decrease on monocytes in iNSIP compared to that in IPF. In contrast, the percentages of S100A9-CD163+ cells were significantly higher in iNSIP patients than in IPF patients and healthy volunteers. In IPF patients, there was a trend toward a correlation between the percentage of S100A9+CD163- monocytes and the surfactant protein-D (SP-D) serum levels (r = 0.4158, [95% confidence interval (CI) - 0.02042-0.7191], p = 0.051). The individual percentages of S100A9+CD163- and S100A9-CD163+ cells were also independently associated with IPF through multivariate regression analysis. The unadjusted area under the receiver operating characteristic curve (ROC-AUC) to discriminate IPF from iNSIP was (ROC-AUC 0.802, 95% CI [0.687-0.928]), suggesting that these are better biomarkers than serum SP-D (p < 0.05). This preliminary study reports the first comparative characterization of monocyte phenotypes between IPF and iNSIP.
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Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Biomarcadores/sangre , Calgranulina B/sangre , Fibrosis Pulmonar Idiopática/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico , Monocitos/metabolismo , Receptores de Superficie Celular/sangre , Anciano , Estudios de Casos y Controles , Diagnóstico Diferencial , Femenino , Humanos , Fibrosis Pulmonar Idiopática/sangre , Enfermedades Pulmonares Intersticiales/sangre , Masculino , Estudios Prospectivos , Curva ROCRESUMEN
Background: Immune non-responders (INR) are HIV+, ART-controlled (>2 yrs) people who fail to reconstitute their CD4 T cell numbers. Systemic inflammation and markers of T cell senescence and exhaustion are observed in INR. This study aims to investigate T cell senescence and exhaustion and their possible association with soluble immune mediators and to understand the immune profile of HIV-infected INR. Selected participants were <50 years old to control for the confounder of older age. Methods: Plasma levels of IL-6, IP10, sCD14, sCD163, and TGF-ß and markers of T cell exhaustion (PD-1, TIGIT) and senescence (CD57, KLRG-1) were measured in ART-treated, HIV+ participants grouped by CD4 T cell counts (n = 63). Immune parameters were also measured in HIV-uninfected, age distribution-matched controls (HC; n = 30). Associations between T cell markers of exhaustion and senescence and plasma levels of immune mediators were examined by Spearman rank order statistics. Results: Proportions of CD4 T cell subsets expressing markers of exhaustion (PD-1, TIGIT) and senescence (CD57, KLRG-1) were elevated in HIV+ participants. When comparing proportions between INR and IR, INR had higher proportions of CD4 memory PD-1+, EM CD57+, TEM TIGIT+ and CD8 EM and TEM TIGIT+ cells. Plasma levels of IL-6, IP10, and sCD14 were elevated during HIV infection. IP10 was higher in INR. Plasma TGF-ß levels and CD4 cycling proportions of T regulatory cells were lower in INR. Proportions of CD4 T cells expressing TIGIT, PD-1, and CD57 positively correlated with plasma levels of IL-6. Plasma levels of TGF-ß negatively correlated with proportions of TIGIT+ and PD-1+ T cell subsets. Conclusions: INR have lower levels of TGF-ß and decreased proportions of cycling CD4 T regulatory cells and may have difficulty controlling inflammation. IP10 is elevated in INR and is linked to higher proportions of T cell exhaustion and senescence seen in INR.
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Linfocitos T CD4-Positivos/inmunología , Senescencia Celular/inmunología , Infecciones por VIH/inmunología , Subgrupos de Linfocitos T/inmunología , Factor de Crecimiento Transformador beta/sangre , Adulto , Antirretrovirales/uso terapéutico , Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Biomarcadores/sangre , Recuento de Linfocito CD4 , Antígenos CD57/sangre , Femenino , Humanos , Interleucina-6/sangre , Lectinas Tipo C/sangre , Receptores de Lipopolisacáridos/sangre , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/sangre , Receptores de Superficie Celular/sangre , Receptores de Citocinas/sangre , Receptores Inmunológicos/sangre , Adulto JovenRESUMEN
BACKGROUND: Circulating monocytes and tissue macrophages play complex roles in the pathogenesis of hypertension and the resulting target organ damage. In this study, we observed alterations in the monocyte phenotype and inflammatory state of hypertensive patients with left ventricular hypertrophy (LVH) and studied the effects of irbesartan in these patients. This study might reveal a novel mechanism by which irbesartan alleviates LVH, and it could provide new targets for the prevention and treatment of hypertensive target organ damage. METHODS: CD163 and CD206 expression on monocytes and IL-10 and TNF-α levels in the serum of hypertensive patients with or without LVH and of healthy volunteers were detected. Furthermore, we treated monocytes from the LVH group with different concentrations of irbesartan, and then, CD163, CD206, IL-10 and TNF-α expression was detected. RESULTS: We found, for the first time, that the expression of CD163, CD206 and IL-10 in the LVH group was lower than that in the non-LVH group and healthy control group, but the TNF-α level in the LVH group was significantly higher. Irbesartan upregulated the expression of CD163 and CD206 in hypertensive patients with LVH in a concentration-dependent manner. Irbesartan also increased the expression of IL-10 and inhibited the expression of TNF-α in monocyte culture supernatants in a concentration-dependent manner. CONCLUSIONS: Our data suggest that inflammation was activated in hypertensive patients with LVH and that the monocyte phenotype was mainly proinflammatory. The expression of proinflammatory factors increased while the expression of anti-inflammatory factors decreased. Irbesartan could alter the monocyte phenotype and inflammatory status in hypertensive patients with LVH. This previously unknown mechanism may explain how irbesartan alleviates LVH. Trail registration The study protocols were approved by the Ethical Committee of the Second Affiliated Hospital of Dalian Medical University. Each patient signed the informed consent form.