RESUMO
Toll-like receptor (TLR) family signature has been implicated in sepsis etiopathology. We aimed to evaluate the genetic profile of TLR pathway-related key genes; the myeloid differentiation protein 88 (MYD88), IL1 receptor-associated kinase 1 (IRAK1), the nuclear factor kappa-B1 (NFKB1), and interleukin 6 (IL6) in the blood of neonates with sepsis at the time of admission and post-treatment for the available paired-samples. This case-control study included 124 infants with sepsis admitted to the neonatal intensive care unit and 17 controls. The relative gene expressions were quantified by TaqMan Real-Time qPCR and correlated to the clinic-laboratory data. MYD88, NFKB1, and IL6 relative expressions were significantly higher in sepsis cases than controls. Higher levels of MYD88 and IL6 were found in male neonates and contributed to the sex-based separation of the cases by the principal component analysis. ROC analysis revealed MYD88 and NFKB1 transcripts to be good biomarkers for sepsis. Furthermore, patients with high circulatory MYD88 levels were associated with poor survival, as revealed by Kaplan-Meier curves analysis. MYD88, NFKB1, and IL6 transcripts showed association with different poor-outcome manifestations. Clustering analysis split the patient cohort into three distinct groups according to their transcriptomic signature and CRP levels. In conclusion, the study TLR pathway-related transcripts have a gender-specific signature, diagnostic, and prognostic clinical utility in neonatal sepsis.
Assuntos
Interleucina-6/sangue , Fator 88 de Diferenciação Mieloide/sangue , Subunidade p50 de NF-kappa B/sangue , Sepse Neonatal/sangue , Sepse Neonatal/mortalidade , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Sepse Neonatal/patologia , Prognóstico , Transdução de Sinais/genéticaRESUMO
OBJECTIVE: Keloids are exuberant cutaneous scars that form due to abnormal growth of fibrous tissue following an injury. The primary aim of this study was to assess the efficacy and mechanism of hyperbaric oxygen therapy (HBOT) to reduce the keloid recurrence rate after surgical excision and radiotherapy. METHODS: (1) A total of 240 patients were randomly divided into two groups. Patients in the HBOT group (O group) received HBOT after surgical excision and radiotherapy. Patients in the other group were treated with only surgical excision and radiotherapy (K group). (2) Scar tissue from recurrent patients was collected after a second operation. Hematoxylin and eosin (H&E) staining was used to observe keloid morphology. Certain inflammatory factors (interleukin-6 (IL-6), hypoxia-inducible factor-1α (HIF-1α), tumor necrosis factor-α (TNF-α), nuclear factor κB (NF-κB), and vascular endothelial growth factor (VEGF)) were measured using immunohistochemical staining. RESULTS: (1) The recurrence rate of the O group (5.97%) was significantly lower than that of the K group (14.15%), P<0.05. Moreover, patients in the O group reported greater satisfaction than those in the K group (P<0.05). (2) Compared with the recurrent scar tissue of the K group, the expression levels of the inflammatory factors were lower in the recurrent scar tissue of the O group. CONCLUSIONS: Adjunctive HBOT effectively reduces the keloid recurrence rate after surgical excision and radiotherapy by improving the oxygen level of the tissue and alleviating the inflammatory process.
Assuntos
Oxigenoterapia Hiperbárica , Queloide/patologia , Queloide/radioterapia , Queloide/cirurgia , Adolescente , Adulto , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Inflamação , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Subunidade p50 de NF-kappa B/sangue , Perfusão , Recidiva , Inquéritos e Questionários , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto JovemRESUMO
BACKGROUND/OBJECTIVES: Given their role in female reproduction, the effects of progesterone on arginine and related amino acids, polyamines and NF-κB p65 activation were studied across the menstrual cycle. METHODS: Arginine, ornithine and citrulline as well as putrescine, spermidine, spermine, and N-acetyl-putrescine were determined in plasma, NF-κB p65 activation in peripheral blood mononuclear cells and progesterone in serum of 28 women at early (T1) and late follicular (T2) and mid (T3) and late (T4) luteal phase. RESULTS: Arginine and related amino acids declined from T1 and T2 to T3 and T4, while progesterone increased. At T3, arginine, ornithine, and citrulline were inversely related with progesterone. Changes (ΔT3-T2) in arginine, ornithine, and citrulline were inversely related with changes (ΔT3-T2) in progesterone. Ornithine and citrulline were positively related with arginine, as were changes (ΔT3-T2) in ornithine and citrulline with changes (ΔT3-T2) in arginine. At T2, NF-κB p65 activation was positively related with arginine. Polyamines did not change and were not related to progesterone. All results described were significant at P < 0.001. CONCLUSIONS: This study for the first time provides data, at the plasma and PBMC level, supporting a proposed regulatory node of arginine and related amino acids, progesterone and NF-κB p65 at luteal phase of the menstrual cycle, aimed at successful preparation of pregnancy.
Assuntos
Arginina/sangue , Fase Luteal/sangue , Progesterona/fisiologia , Adulto , Aminoácidos/sangue , Citrulina/metabolismo , Feminino , Fase Folicular , Voluntários Saudáveis , Humanos , Leucócitos Mononucleares/citologia , Subunidade p50 de NF-kappa B/sangue , Ornitina/metabolismo , Putrescina/metabolismo , Valores de Referência , Espermidina/metabolismo , Espermina/metabolismo , Fator de Transcrição RelA/sangueRESUMO
Background To investigate the relationship between the levels of nuclear factor (NF)-κB p50 and NF-κB p65 and tumour characteristics in patients with thyroid carcinoma. Methods This prospective study enrolled consecutive patients with thyroid carcinoma. Tumour samples were collected and the levels of NF-κB p50 and NF-κB p65 protein and mRNA were measured using immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Results A total of 73 patients with thyroid carcinoma were included in the study (20 males; 53 females; mean ± SD age, 44.8 ± 12.7 years, range, 18-76 years). There were no significant differences in sex, age and pathological type between the NF-κB p50 positive group and the NF-κB p50 negative group, but tumour diameter and lymph node metastasis were significantly higher in the NF-κB p50 positive group compared with the NF-κB p50 negative group. Similar findings were observed for NF-κB p65. The levels of NF-κB p50 were positively correlated with NF-κB p65 in samples of thyroid carcinoma ( rs = 0.653). Conclusion The levels of NF-κB p50 and NF-κB p65 in samples of thyroid carcinoma were positively associated with tumour diameter and the presence of lymph node metastasis.
Assuntos
Subunidade p50 de NF-kappa B/sangue , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologia , Fator de Transcrição RelA/sangue , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Mensageiro/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias da Glândula Tireoide/metabolismo , Adulto JovemRESUMO
McKinley-Barnard, SK, Andre, TL, Gann, JJ, Hwang, PS, and Willoughby, DS. Effectiveness of fish oil supplementation in attenuating exercise-induced muscle damage in females during midfollicular and midluteal menstrual phases. J Strength Cond Res 32(6): 1601-1612, 2018-The purpose of this study was to determine whether the differences in estrogen levels during the female menstrual cycle and fish oil supplementation would attenuate eccentric exercise-induced muscle damage and delayed-onset muscle soreness (DOMS). In a double-blind fashion, 22 physically active females (20.9 ± 1.4 years, 63.5 ± 9.0 kg, 165.2 ± 7.5 cm) were randomly assigned to ingest either 6 g of fish oil (n = 11) or placebo (n = 11) daily for 21 days. Participants underwent an eccentric exercise bout of the knee extensors on 2 occasions during the midfollicular (MF) and midluteal (ML) phases of the 28-day menstrual cycle. Before (PRE), at 6 (6HRPOST), and at 24 hours postexercise (24HRPOST) for each session, participants underwent assessments of DOMS, muscle strength, and had venous blood samples and muscle biopsies obtained. Data were analyzed using a 2 × 2 × 3 repeated-measures multivariate analysis of variance for each criterion variable (p ≤ 0.05). Further analysis of the main effects for the test was performed using separate 1-way analyses of variance. Delayed-onset muscle soreness was significantly greater at the 6HRPOST and 24HRPOST timepoints compared with PRE (p < 0.001). Superoxide dismutase and tumor necrosis factor-alpha (TNF-α) concentrations were significantly higher at the MF phase compared with the ML phase (p < 0.001 and p = 0.05, respectively). There were no statistically significant differences observed for muscle strength, myoglobin, NF-Kß p50, or NF-Kß p65. This study demonstrates that higher levels of estrogen may exert a cytoprotective effect on the sarcolemma.
Assuntos
Exercício Físico , Óleos de Peixe/uso terapêutico , Fase Folicular/sangue , Fase Luteal/sangue , Mialgia/prevenção & controle , Músculo Quadríceps/patologia , Adulto , Biópsia , Suplementos Nutricionais , Método Duplo-Cego , Estradiol/sangue , Feminino , Humanos , Masculino , Força Muscular , Mialgia/etiologia , Mioglobina/sangue , Subunidade p50 de NF-kappa B/sangue , Músculo Quadríceps/fisiologia , Superóxido Dismutase/sangue , Fator de Transcrição RelA/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
Hepatic ischemia/reperfusion injury (IRI) and associated inflammation contributes to liver dysfunction and complications after liver surgery and transplantation. Mesenchymal stem cells (MSCs) have been reported to reduce hepatic IRI because of their reparative immunomodulatory effects in injured tissues. Recent studies have highlighted beneficial effects of extracellular vesicles from mesenchymal stem cells (MSC-EV) on tissue injury. The effects of systemically administered mouse bone marrow-derived MSC-EV were evaluated in an experimental murine model of hepatic IRI induced by cross-clamping the hepatic artery and portal vein for 90 minutes followed by reperfusion for periods of up to 6 hours. Compared with controls, intravenous administration of MSC-EV 30 minutes prior to IRI dramatically reduced the extent of tissue necrosis, decreased caspase 3-positive and apoptotic cells, and reduced serum aminotransferase levels. MSC-EV increased hepatic messenger RNA (mRNA) expression of NACHT, LRR, and PYD domains-containing protein 12, and the chemokine (C-X-C motif) ligand 1, and reduced mRNA expression of several inflammatory cytokines such as interleukin 6 during IRI. MSC-EV increased cell viability and suppressed both oxidative injury and nuclear factor kappa B activity in murine hepatocytes in vitro. In conclusion, the administration of extracellular vesicles derived from bone marrow-derived MSCs may ameliorate hepatic IRI by reducing hepatic injury through modulation of the inflammatory response.Liver Transplantation 23 791-803 2017 AASLD.
Assuntos
Células da Medula Óssea/citologia , Vesículas Extracelulares , Fígado/patologia , Células-Tronco Mesenquimais/citologia , Traumatismo por Reperfusão/terapia , Animais , Apoptose , Caspase 3/metabolismo , Sobrevivência Celular , Quimiocina CXCL1/sangue , Artéria Hepática/patologia , Hepatócitos/citologia , Hipóxia , Inflamação , Interleucina-6/sangue , Peptídeos e Proteínas de Sinalização Intracelular/sangue , Transplante de Células-Tronco Mesenquimais , Camundongos , Camundongos Endogâmicos C57BL , Subunidade p50 de NF-kappa B/sangue , Necrose , Estresse Oxidativo , Oxigênio/química , Oxigênio/metabolismo , Veia Porta/patologia , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/patologia , Transaminases/sangueRESUMO
Head and neck squamous cell carcinoma (HNSCC) is the major health concern in Indian population. Despite of advanced treatment the mortality rate for this disease has not been improved very much. Current research focused on development of protein marker for the diagnosis and prognosis of HNSCC. The case control study was performed with 125 HNSCC patients and 104 control cases. The level of p50 and IκBα proteins in serum were evaluated at pre and post therapy by label free real time surface plasmon resonance (SPR) and western blot analysis. The serum p50 concentration were significantly (P < 0.0001) higher at the time of diagnosis i.e. pre therapy (Mean ± SD = 27.06 ± 4.88 ng/µl) as compared to controls (Mean ± SD = 16.96 ± 4.04 ng/µl) while it decline at post therapy (Mean ± SD = 21.01 ± 4.98 ng/µl). Similarly, the concentration of IκBα protein in serum were slightly higher at pre therapy (Mean ± SD = 8.33 ± 1.85 ng/µl) as compared to controls (Mean ± SD = 7.27 ± 1.84 ng/µl) and declined at post therapy (Mean ± SD = 7.09 ± 1.24 ng/µl). The level of p50 was also high at the early stage of the disease. The specificity and sensitivity of p50 proteins obtained from ROC analysis revealed the potentiality to be diagnostic protein marker for HNSCC for its accuracy in the study cohort.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/diagnóstico , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/diagnóstico , Subunidade p50 de NF-kappa B/sangue , Adulto , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Proteínas I-kappa B/sangue , Proteínas I-kappa B/genética , Masculino , Pessoa de Meia-Idade , Inibidor de NF-kappaB alfa , Subunidade p50 de NF-kappa B/genética , Gradação de Tumores , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Curva ROC , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND: Preterm prelabor rupture of the fetal membranes (PPROM) is a significant contributor to the morbidity and mortality of preterm birth, particularly in the setting of chorioamnionitis. No sensitive or specific diagnostic or predictive test currently exists for the accurate diagnosis of chorioamnionitis. Our aim was to measure messenger RNA (mRNA) coding cytokines in the maternal blood and examine whether they were increased in association with chorioamnionitis at delivery. METHODS/RESULTS: We performed a prospective cohort study of women recruited with PPROM at a mean gestational age of 28.9 weeks at risk of developing chorioamnionitis. Blood was sampled from participants, and the expression of mRNA coding for proinflammatory genes was measured in women with and without chorioamnionitis at the time of delivery as well as gestation-matched healthy controls. Expression was measured using quantitative polymerase chain reaction (PCR) and also digital PCR. Interleukin 1ß (IL1B) mRNA expression in maternal blood was elevated in women with chorioamnionitis compared to gestation-matched controls. Importantly, among women admitted with PPROM, digital PCR confirmed a significant increase in IL1B expression in maternal blood in women with chorioamnionitis compared to women without chorioamnionitis. Polymerase chain reaction array revealed that CD14, nuclear factor of κ light polypeptide gene enhancer in B-cells 1 (NFKB1), and tumor necrosis factor receptor super family-interacting serine-threonine kinase 1 mRNA were significantly increased in women with chorioamnionitis compared to controls. Digital PCR confirmed that NFKB1 mRNA was significantly increased in patients with chorioamnionitis compared to controls and that CD14 levels increased over time in patients with PPROM having chorioamnionitis. CONCLUSION: Measuring circulating proinflammatory mRNA in women with PPROM may distinguish those with chorioamnionitis from those without, in turn providing better targeted therapies and appropriate timing of delivery.
Assuntos
Corioamnionite/genética , Citocinas/genética , Ruptura Prematura de Membranas Fetais/genética , Circulação Placentária/genética , RNA Mensageiro/genética , Adulto , Biomarcadores/sangue , Corioamnionite/sangue , Corioamnionite/diagnóstico , Estudos de Coortes , Citocinas/sangue , Feminino , Ruptura Prematura de Membranas Fetais/sangue , Ruptura Prematura de Membranas Fetais/diagnóstico , Humanos , Interleucina-1beta/sangue , Interleucina-1beta/genética , Receptores de Lipopolissacarídeos/sangue , Receptores de Lipopolissacarídeos/genética , Subunidade p50 de NF-kappa B/sangue , Subunidade p50 de NF-kappa B/genética , Gravidez , Estudos Prospectivos , RNA Mensageiro/sangue , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genéticaRESUMO
OBJECTIVE: Despite of the common usage of glucocorticoids (GCs), a significant portion of asthma patients exhibit GC insensitivity. This could be mediated by diverse mechanisms, including genomics. Recent work has suggested that measuring changes in gene expression may provide more predictive information about GC insensitivity than baseline gene expression alone, and that expression changes in peripheral blood may be reflective of those in the airway. METHODS: We performed in silico discovery using gene expression omnibus (GEO) data that evaluated GC effect on gene expression in multiple tissue types. Subsequently, candidate genes whose expression levels are affected by GC were examined in cell lines and in primary cells derived from human airway and blood. RESULTS: Through gene expression omnibus analysis, we identified interferon regulator factor 1 (IRF1), whose expression is affected by GC treatment in airway smooth muscle cells, normal human bronchial epithelial (NHBE) cells, and lymphoblastoid cell lines (LCLs). Significant IRF1 downregulation post GC exposure was confirmed in two cultured airway epithelial cell lines and primary NHBE cells (P<0.05). We observed large interindividual variation in GC-induced IRF1 expression changes among primary NHBE cells tested. Significant downregulation of IRF1 was also observed in six randomly selected LCLs (P<0.05), with variable degrees of downregulation among different samples. In peripheral blood mononuclear cells obtained from healthy volunteers, variable downregulation of IRF1 by GC was also shown. NFKB1, a gene whose expression is known to be downregulated by GC and the degree of downregulation of which is reflective of GC response, was used as a control in our study. IRF1 shows more consistent downregulation across tissue types when compared with NFKB1. CONCLUSION: Our results suggest that GC-induced IRF1 gene expression changes in peripheral blood could be used as a marker to reflect GC response in the airway.
Assuntos
Dexametasona/farmacologia , Glucocorticoides/farmacologia , Fator Regulador 1 de Interferon/sangue , Subunidade p50 de NF-kappa B/sangue , Biomarcadores/sangue , Células Cultivadas , Bases de Dados Genéticas , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Sistema Respiratório/citologiaRESUMO
BACKGROUND: Skeletal muscle weakness in chronic obstructive pulmonary disease (COPD) carries a poor prognosis, therefore a non-invasive marker of this process could be useful. Reduced expression of muscle-specific microRNA (myomiRs) in quadriceps muscle in patients with COPD is associated with skeletal muscle weakness and changes in muscle fibre composition. Circulating exosomal miRNAs can be measured in blood, making them candidate biomarkers of biopsy phenotype. To determine whether plasma myomiR levels were associated with fibre size or fibre proportion, we measured myomiRs in plasma from patients with COPD and healthy controls. METHODS AND RESULTS: 103 patients with COPD and 25 age-matched controls were studied. Muscle-specific miRNA was elevated in the plasma of patients with COPD and showed distinct patterns. Specifically, miR-1 was inversely associated with fat-free mass in the cohort, whereas levels of miR-499 were more directly associated with strength and quadriceps type I fibre proportion. Two miRs not restricted to muscle in origin (miR-16 and miR-122) did not differ between patients and controls. Plasma miR-499 was also associated with muscle nuclear factor κB p50 but not p65 in patients with early COPD whereas plasma inflammatory cytokines were associated with miR-206 in patients with more advanced disease. CONCLUSIONS: Plasma levels of individual myomiRs are altered in patients with COPD but alone do not predict muscle fibre size or proportion. Our findings are consistent with an increase in muscle wasting and turnover associated with the development of skeletal muscle dysfunction and fibre-type shift in patients with stable COPD.
Assuntos
MicroRNAs/sangue , Debilidade Muscular/sangue , Debilidade Muscular/patologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/complicações , Músculo Quadríceps/metabolismo , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Musculares de Contração Lenta/patologia , Força Muscular , Debilidade Muscular/etiologia , Subunidade p50 de NF-kappa B/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fator de Transcrição RelA/sangueRESUMO
OBJECTIVES: The receptor activator of the nuclear factor kappa-B (NF-κB) ligand (RANKL), its membrane receptor RANK and its decoy receptor osteoprotegerin (OPG) are all members of the tumour necrosis factor family involved in bone metabolism and immune response. We evaluated the activation of the OPG/RANKL/RANK pathway in patients undergoing cardiac surgery with and without cardiopulmonary bypass (CPB). METHODS: Twenty consecutive patients undergoing elective coronary artery surgery were enrolled in the study and assigned either to the on-pump or to the off-pump group. Pre- and postoperative serum levels of OPG and RANKL were evaluated by enzyme-linked immunosorbent assay; gene expression of OPG, RANKL, RANK and NF-κB p50 subunits were determined by real-time polymerase chain reaction in peripheral blood T-cells and monocytes. RESULTS: Serum levels of OPG significantly increased after surgery in both groups, whereas serum levels of RANKL did not differ over time. T-cells from the on-pump group showed increased gene expression of OPG, RANKL and RANK after the intervention, whereas no mRNA variation for these genes was detected in T-cells from off-pump patients. Gene expression of p50 subunit increased in T-cells and monocytes from both groups. CONCLUSIONS: Cardiac surgery induces the activation of the OPG/RANKL/RANK pathway; both on- and off-pump procedures are associated with increased postoperative OPG serum levels and up-regulation of the NF-κB p50 subunit.
Assuntos
Ponte de Artéria Coronária/métodos , Subunidade p50 de NF-kappa B/sangue , Osteoprotegerina/sangue , Ligante RANK/sangue , Receptor Ativador de Fator Nuclear kappa-B/sangue , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Ensaio de Imunoadsorção Enzimática , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Subunidade p50 de NF-kappa B/genética , Osteoprotegerina/genética , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Transdução de SinaisRESUMO
OBJECTIVE: In patients with obesity and type 2 diabetes, the changes in insulin resistance are associated with the changes in expression of genes involved in nuclear factor-κB (NF-κB) activation in peripheral blood mononuclear cells (PBMCs). As such studies have never been carried out in patients with gestational diabetes (GDM), in this study, we evaluated the expression of genes involved in NF-κB activation and related to glucose metabolism in PBMCs obtained from pregnant women with GDM and normal glucose tolerance (NGT). DESIGN AND METHODS: RT-PCR was performed in 60 pregnant women divided into three groups: GDM at the 1st visit, i.e. in the 24th-28th weeks of gestation (GDM1), NGT at the first visit and GDM in the 29th-32nd weeks (GDM2), and NGT at both visits. The tests were repeated 3 months postpartum. RESULTS: The GDM1 group had significantly higher TLR2 (P=0.024), TLR4 (P=0.037), STAT1 (P=0.027), and CX3CL1 (P=0.017) mRNA expression, whereas the GDM2 group showed markedly lower TNFRSF1A (P=0.042), PPARG (P=0.018), STAT3 (P=0.013), and CX3CL1 (P=0.038) mRNA expression in comparison with the NGT group. The women with NGT at the 1st visit who later developed GDM had significantly higher fasting glucose (P=0.01), HOMA-IR (P=0.004), and TLR2 mRNA expression (P=0.04), as well as lower ISSI2 (P=0.01) and disposition indices, DI30 (P=0.03) and DI120 (P=0.01), than had the women who remained normoglycemic. CONCLUSIONS: Our results suggest that elevated TLR2 expression, as well as higher fasting glucose and lower compensation for increased insulin resistance, may represent early metabolic disturbances in the development of GDM.
Assuntos
Diabetes Gestacional/sangue , Diabetes Gestacional/metabolismo , Regulação da Expressão Gênica , Leucócitos Mononucleares/metabolismo , Subunidade p50 de NF-kappa B/sangue , Receptor 2 Toll-Like/metabolismo , Adulto , Glicemia/análise , Quimiocina CX3CL1/genética , Quimiocina CX3CL1/metabolismo , Diabetes Gestacional/diagnóstico , Diagnóstico Precoce , Feminino , Humanos , Resistência à Insulina , Subunidade p50 de NF-kappa B/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , RNA Mensageiro/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
The modulation of CD40L activity might represent a promising therapeutic target to reduce monocyte inflammatory functions in chronic diseases, such as rheumatoid arthritis. In the present study, we investigated the possible influence of nonsteroidal anti-inflammatory drugs (NSAIDs) on CD40L-induced monocyte survival. Monocytes were isolated from buffy coats by using Ficoll-Percoll gradients. Monocyte apoptosis was evaluated by fluorescence microscopy on cytopreps stained with acridine orange or using flow cytometry analysis of Annexin-V and Propidium Iodide staining. Akt and NF-kappaB activation was assessed using western blot. Caspase 3 activity was determined spectrophotometrically. Among different NSAIDs, only oxaprozin dose-dependently increased apoptosis of CD40L-treated monocytes. Oxaprozin pro-apoptotic activity was associated with the inhibition of CD40L-triggered Akt and NF-kappaB phosphorylation and the activation of caspase 3. In conclusion, our data suggest that oxaprozin-induced apoptosis in CD40L-treated human monocytes is associated with previously unknown cyclooxygenase (COX)-independent pathways. These intracellular proteins might be promising pharmacological targets to increase apoptosis in CD40L-treated monocytes.