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Article in English | WPRIM | ID: wpr-929048


Ovarian cancer is the third-most-common malignant reproductive tumor in women. According to the American Cancer Society, it has the highest mortality rate of gynecological tumors. The five-year survival rate was only 29% during the period from 1975 to 2008 (Reid et al., 2017). In recent decades, the five-year survival rate of ovarian cancer has remained around 30% despite continuous improvements in surgery, chemotherapy, radiotherapy, and other therapeutic methods. However, because of the particularity of the volume and location of ovarian tissue, the early symptoms of ovarian cancer are hidden, and there is a lack of highly sensitive and specific screening methods. Most patients have advanced metastasis, including abdominal metastasis, when they are diagnosed (Reid et al., 2017). Therefore, exploring the mechanism of ovarian cancer metastasis and finding early preventive measures are key to improving the survival rate and reducing mortality caused by ovarian cancer.

B7-H1 Antigen/biosynthesis , Cell Proliferation/drug effects , Chemokines/biosynthesis , Female , Humans , Ovarian Neoplasms/pathology , Survival Rate , Up-Regulation
Arq. bras. cardiol ; 117(4): 715-725, Oct. 2021. tab, graf
Article in Portuguese | LILACS | ID: biblio-1345249


Resumo Fundamentos A L-carnitina (LC) tem muitos efeitos benéficos em animais diabéticos e humanos, mas seu efeito regulatório sobre a quemerina como uma citocina inflamatória e seu receptor no estado diabético são desconhecidos. Objetivos O presente estudo teve como objetivo investigar o efeito regulatório da LC na expressão do receptor semelhante ao de quimiocina 1 e quemerina (CMKLRI) em tecidos adiposo e cardíaco de camundongos diabéticos. Métodos Sessenta camundongos NMARI foram divididos em quatro grupos, incluindo controle, diabético, diabético + suplementação com LC e controle + suplementação com LC. O diabetes foi induzido pela alimentação dos animais com dieta hipercalórica por 5 semanas e injeção de estreptozotocina. Os animais foram tratados com 300 mg/kg de LC por 28 dias. Nos dias 7, 14 e 28 após o tratamento, os níveis de mRNA e proteína da quemerina e CMKLRI nos tecidos cardíacos e adiposos de animais foram determinados utilizando análise por qPCR e ELISA. Os índices de resistência à insulina também foram medidos em todos os grupos experimentais. A diferença com p<0,05 foi considerada significativa. Resultados A expressão de quemerina e CMKLRI aumentou nos tecidos cardíaco e adiposo de camundongos diabéticos nos dias 14 e 28 após a indução do diabetes, concomitantemente com a incidência de resistência à insulina e níveis aumentados de quemerina circulante (p<0,05). O tratamento com LC causou uma diminuição significativa na expressão de ambos os genes nos tecidos estudados e redução dos sintomas de resistência à insulina e dos níveis séricos de quemerina (p<0,05). Conclusão Os resultados sugerem que o tratamento com LC pode diminuir a expressão de quemerina e CKLR1 em tecidos cardíacos e adiposos de animais experimentais obesos e diabéticos.

Abstract Background L-carnitine (LC) has many beneficial effects on diabetic animals and humans, but its regulatory effect on chemerin as an inflammatory cytokine, and its receptor in diabetes status is unknown. Objectives The present study aimed to investigate the regulatory effect of LC on the expression of chemerin and chemokine-like receptor I (CMKLRI) in adipose and cardiac tissues of diabetic mice. Methods Sixty NMARI mice were divided into four groups including control, diabetic, diabetic + LC supplementation and control + LC supplementation. Diabetes was induced by feeding the animals a high-calorie diet for 5 weeks and injection of Streptozotocin. The animals were treated with 300 mg/kg LC for 28 days. On days 7, 14, and 28 after treatment, the mRNA and protein levels of chemerin and CMKLRI in the cardiac and adipose tissues of the animals were determined using qPCR analysis and ELISA. Insulin resistance indices were also measured in all experimental groups. Differences with p <0.05 were considered significant. Results Chemerin and CMKLRI expressions levels were increased in cardiac and adipose tissues of diabetic mice on days 14 and 28 after diabetes induction, concurrent with the incidence of insulin resistance and increased levels of circulating chemerin (p<0.05). The treatment with LC caused a significant decrease in the expression of both genes in studied tissues and the reduction of insulin resistance symptoms and serum chemerin levels (p<0.05). Conclusion The results suggest that LC treatment were able to downregulate the expression of chemerin and CKLR1 in cardiac and adipose tissues of obese, diabetic experimental animals.

Animals , Mice , Receptors, Chemokine , Diabetes Mellitus, Experimental/drug therapy , Carnitine/pharmacology , Chemokines , Intercellular Signaling Peptides and Proteins , Mice, Obese , Obesity/drug therapy
Arq. neuropsiquiatr ; 79(9): 789-794, Sept. 2021. tab
Article in English | LILACS | ID: biblio-1345328


Abstract Background: Migraines are headaches caused by changes in the trigeminovascular metabolic pathway. Migraine headache attacks are associated with neurovascular inflammation, but their pathophysiological mechanisms have not been fully explained. Objective: To investigate the relationship between serum vaspin, visfatin, chemerin and interleukin-18 (IL-18) levels and the frequency of attacks in migraine headache. Methods: Three groups were established: migraine with aura (n = 50), migraine without aura (n = 50) and control group (n = 50). The migraine diagnosis was made in accordance with the International Classification of Headache Disorders-III beta diagnostic criteria. The analyses on serum vaspin, visfatin, chemerin and IL-18 levels were performed using the enzyme-linked immunosorbent assay method. Results: The serum vaspin, visfatin, chemerin and IL-18 levels were found to be significantly higher in the migraine patients than in the control group (p < 0.01). No statistically significant differences in serum vaspin, visfatin, chemerin and IL-18 levels were found among the migraine patients during attacks or in the interictal period (p>0.05). The serum visfatin and chemerin levels of the migraine patients were positively correlated with their serum IL-18 levels (p < 0.01), while their serum chemerin and visfatin levels were positively correlated with their serum vaspin levels (p < 0.05). Conclusions: This study showed that these biomarkers may be related to migraine pathogenesis. Nonetheless, we believe that more comprehensive studies are needed in order to further understand the role of vaspin, visfatin, chemerin and IL-18 levels in the pathophysiology of migraine headaches.

Resumo Introdução: A migrânea é causada por alterações nas vias metabólicas do sistema trigeminovascular. Crises de migrânea estão associadas à inflamação neurovascular, mas seus mecanismos patofisiológicos ainda não são totalmente explicados. Objetivo: Investigar a relação entre níveis séricos de vaspina, visfatina, quemerina e interleucina-18 (IL-18) e a frequência de crises de migrânea. Métodos: Três grupos foram formados: migrânea com aura (n = 50), migrânea sem aura (n = 50) e grupo controle (n = 50). A migrânea foi diagnosticada de acordo com os critérios da Classificação Internacional das Cefaleias (ICHD-III). As análises dos níveis séricos de vaspina, visfatina, quemerina e IL-18 foram realizadas utilizando-se o método imunoenzimático (ELISA). Resultados: Os níveis séricos de vaspina, visfatina, quemerina e interleucina-18 (IL-18) foram significativamente mais elevados em pacientes com migrânea do que no grupo controle (p < 0.01). Nenhuma diferença estatisticamente significativa foi observada nos níveis séricos de vaspina, visfatina, quemerina e interleucina-18 (IL-18) entre os pacientes com migrânea durante crises ou no período interictal (p>0,05). Os níveis séricos de visfatina e quemerina em pacientes com migrânea se correlacionaram positivamente com os níveis séricos de IL-18 (p < 0,01), ao passo que os níveis séricos de quemerina e visfatina se correlacionaram positivamente com os níveis séricos de vaspina (p < 0,05). Conclusões: Este estudo demonstrou que estes biomarcadores podem estar relacionados à patogênese da migrânea. Contudo, acreditamos que estudos mais abrangentes são necessários a fim de melhor compreendermos o papel dos níveis de vaspina, visfatina, quemerina e IL-18 na fisiopatologia da migrânea.

Humans , Insulin Resistance , Serpins , Migraine Disorders , Chemokines , Interleukin-18 , Nicotinamide Phosphoribosyltransferase
Arq. neuropsiquiatr ; 79(3): 189-194, Mar. 2021. tab, graf
Article in English | LILACS | ID: biblio-1285337


ABSTRACT Background: Elevated levels of chemerin can predict future ischemic cerebrovascular disease. Although chemerin is thought to play a role in atherosclerotic inflammation, whether circulating chemerin levels are associated with the severity of atherosclerosis remains to be determined. Objectives: Through the use of carotid Doppler ultrasonography, our aim in this study was to investigate the relationships of serum chemerin levels with carotid intima-media thickness (CIMT) as an indicator of generalized atherosclerosis. Methods: This study compared 40 patients with ischemic stroke and 40 healthy subjects. Measurements were made at end-diastole using color Doppler ultrasonography (CDUS) after a 5-min rest interval in a quiet and dark room. CIMT was defined as the distance between the innermost edge of the luminal echo to the innermost edge of the media/adventitia echo. CIMT was measured in the posterior wall of both common carotid arteries within 1 cm proximally to the bulbus. Three measurements were made on both sides and the average measurement was taken as the CIMT. Serum chemerin levels were determined in all patients and healthy subjects. Results: Serum chemerin levels were significantly higher in the patient group than in the control group (p=0.004). Serum chemerin levels were positively correlated with CIMT (p<0.05). There was a significant difference between the groups with regard to CIMT (p<0.001). Conclusion: Elevated serum chemerin levels appear to be associated with CIMT, thus suggesting that a link exists between chemerin and atherosclerotic ischemic cerebrovascular disease.

RESUMO Introdução: Níveis elevados de chemerin podem prever doenças cerebrovasculares isquêmicas futuras. Embora se acredite que a chemerin desempenhe um papel na inflamação aterosclerótica, ainda não foi determinado se os níveis circulantes de chemerin estão associados à gravidade da aterosclerose Objetivos: Por meio do uso da ultrassonografia Doppler da carótida, nosso objetivo neste estudo foi investigar as relações dos níveis séricos de chemerin com a espessura da íntima-média da carótida (EIMC) como um indicador de aterosclerose generalizada. Métodos: Este estudo comparou 40 pacientes com AVC isquêmico e 40 indivíduos saudáveis. As medidas foram feitas no final da diástole usando ultrassonografia Doppler em cores (USDC), após um intervalo de descanso de 5 minutos em um quarto silencioso e escuro. A EIMC foi definida como a distância entre a borda mais interna do eco luminal e a borda mais interna do eco da mídia/adventícia. EIMC foi medido na parede posterior de ambas as artérias carótidas comuns dentro de 1 cm proximalmente ao bulbo. Três medições foram feitas em ambos os lados e a medição média foi tomada como o EIMC. Os níveis séricos de chemerin foram determinados em todos os pacientes e indivíduos saudáveis. Resultados: Os níveis séricos de chemerin foram significativamente maiores no grupo de pacientes do que no grupo controle (p=0,004). Os níveis séricos de chemerin foram positivamente correlacionados com EIMC (p<0,05). Houve diferença significativa entre os grupos em relação à EIMC (p<0,001). Conclusão: Níveis séricos elevados de chemerin parecem estar associados com a EIMC, sugerindo que existe uma ligação entre chemerin e doença cerebrovascular isquêmica aterosclerótica.

Humans , Carotid Artery Diseases/diagnostic imaging , Chemokines/blood , Atherosclerosis , Carotid Intima-Media Thickness , Carotid Arteries/diagnostic imaging , Risk Factors , Ultrasonography , Carotid Artery, Common/diagnostic imaging
Rev. cuba. hematol. inmunol. hemoter ; 37(1): e1101, ene.-mar. 2021. graf
Article in Spanish | LILACS, CUMED | ID: biblio-1251718


Introducción: Las quimiocinas son proteínas secretadas con tamaño en el rango de 8-10 kDa, con numerosas funciones en la fisiología normal y patológica. El término deriva de las palabras citocinas quimiotácticas, que refleja su importante participación en la quimioatracción de leucocitos. Sin embargo, las evidencias muestran que las quimiocinas tienen muchas otras funciones como la comunicación intercelular, la activación celular y la regulación del ciclo celular. Objetivo: Analizar los conocimientos actuales sobre las quimiocinas y sus receptores, y la significación clínica de estas en la medicina transfusional y el trasplante. Métodos: Se realizó revisión de la literatura, en inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico de artículos publicados en los últimos 10 años. Se efectuó análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: La transcripción de la mayoría de los genes de quimiocinas es inducible y se produce en respuesta a estímulos celulares específicos. Las quimiocinas son importantes en la movilización de células progenitoras hematopoyéticas para el trasplante y localización de células progenitoras hematopoyéticas trasplantadas. En los modelos de incompatibilidad ABO, las quimiocinas CXC y CC se producen en niveles elevados. Conclusiones: Muchas son las oportunidades de futuras investigaciones sobre las quimiocinas en la medicina transfusional por la considerable redundancia y superposición en la función biológica de estas moléculas y sus receptores. Son solo una parte de un proceso mucho más grande y complejo dentro de la red de citoquinas y otras moléculas del sistema inmune(AU)

Introduction: Chemokines are secreted proteins with size in the range of 8-10 kDa, with numerous functions in normal and pathological physiology. The term derives from the words chemotactic cytokines, reflecting its important role in the chemoattraction of leukocytes. However, the evidence shows that chemokines have many other functions such as intercellular communication, cell activation and cell cycle regulation. Objetive: To present current knowledge about chemokines and their receptors, and the clinical significance of these in transfusion medicine and transplantation. Method: A review of the literature was made, in English and Spanish, through the PubMed website and the Google academic search engine of articles published in the last 10 years. An analysis and summary of the revised bibliography was made. Developing: The transcription of most of the chemokine genes is inducible and occurs in response to specific cellular stimuli. Chemokines play an important role in the mobilization of hematopoietic progenitor cells for the transplantation and localization of transplanted hematopoietic progenitor cells. In the ABO incompatibility models, the CXC and CC chemokines are produced at high levels. Conclusions: There are many opportunities for future research on chemokines in transfusion medicine due to their considerable redundancy and superposition in the biological function of these molecules and their receptors. They are just one part of a much larger and more complex process within the network of cytokines and other molecules of the immune system(AU)

Cytokines , Chemokines , Transfusion Medicine , Immune System
Clinics ; 76: e1713, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153987


OBJECTIVES: The chemokine ligand (CCL) 21 regulates the maturation, migration, and function of dendritic cells, and has been implicated in the pathogenesis of asthma. This study aimed to investigate the association between serum CCL21 levels and asthma control. METHODS: The serum levels of CCL21 and other inflammatory cytokines were analyzed in patients with asthma (n=44) and healthy controls (n=35) by enzyme-linked immunosorbent assay. IgE levels and eosinophil counts were determined by turbidimetric inhibition immunoassay and fully automatic blood analysis, respectively. The Asthma Control Test (ACT) questionnaire was used, and spirometry and fractional exhaled nitric oxide (FENO) measurements were performed. A multiple unpaired Student's t-test was performed to analyze the differences in CCL21 and interleukin levels between patients with asthma and healthy controls. The correlation of CCL21 levels with disease severity was evaluated using the Pearson's rank correlation test. RESULTS: Serum CCL21 levels were lower in patients with asthma (254.78±95.66 pg/mL) than in healthy controls (382.95±87.77 pg/mL) (p<0.001). Patients with asthma had significantly higher levels of IL-1β (19.74±16.77 vs. 2.63±5.22 pg/mL), IL-6 (7.55±8.65 vs. 2.37±2.47 pg/mL), and tumor necrosis factor-α (12.70±12.03 vs. 4.82±3.97 pg/mL) compared with the controls. CCL21 levels were positively correlated with the ACT score (rs=0.1653, p=0.0062), forced expiratory volume in 1s (FEV1)/forced vital capacity (rs=0.3607, p<0.0001), and FEV1 (rs=0.2753, p=0.0003), and negatively correlated with FENO (rs=0.1060, p=0.0310). CCL21 levels were negatively correlated with serum IgE levels (rs=0.1114, p=0.0268) and eosinophil counts (rs=0.3476, p<0.0001). CONCLUSIONS: Serum CCL21 levels may be a new biomarker for assessing asthma control.

Humans , Adult , Asthma , Chemokine CCL21/blood , Forced Expiratory Volume , Chemokines , Exhalation , Ligands , Nitric Oxide
Article in English | WPRIM | ID: wpr-888489


OBJECTIVES@#To study the expression of adipokines in children with primary nephrotic syndrome (PNS) before and after treatment and its correlation with blood lipids, as well as the role of adipokines in PNS children with hyperlipidemia.@*METHODS@#A total of 90 children who were diagnosed with incipient PNS or recurrence of PNS after corticosteroid withdrawal for more than 6 months were enrolled as subjects. Thirty children who underwent physical examination were enrolled as the control group. Venous blood samples were collected from the children in the control group and the children with PNS before corticosteroid therapy (active stage) and after urinary protein clearance following 4 weeks of corticosteroid therapy (remission stage). ELISA was used to measure the levels of adipokines. An automatic biochemical analyzer was used to measure blood lipid levels.@*RESULTS@#Compared with the control group, the children with PNS had a significantly lower level of omentin-1 in both active and remission stages, and their level of omentin-1 in the active stage was significantly lower than that in the remission stage (@*CONCLUSIONS@#Omentin-1 may be associated with disease activity, dyslipidemia, and proteinuria in children with PNS. Blood lipid ratios may be more effective than traditional blood lipid parameters in monitoring early cardiovascular risk in children with PNS.

Adipokines , Chemokines , Child , Cytokines/metabolism , GPI-Linked Proteins/metabolism , Humans , Hyperlipidemias , Lectins/metabolism , Lipids , Nephrotic Syndrome/drug therapy , Proteinuria
Article in Chinese | WPRIM | ID: wpr-878709


Adipokines,the bioactive polypeptides secreted by adipose tissue,are related to the occurrence and development of obesity,metabolic syndrome,renal insufficiency,cardiovascular disease,diabetes mellitus and other diseases.They may be the disease intervention targets and a breakthrough in the study of disease pathogenesis.In this paper,we summarize the latest research progress of the adipokines omentin,chemerin and nesfatin.

Adipokines , Adipose Tissue , Chemokines , Cytokines , Humans , Kidney Diseases , Metabolic Syndrome , Obesity
J. bras. nefrol ; 42(3): 280-289, July-Sept. 2020. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1134858


ABSTRACT Introduction: Glomerular hyperfiltration may lead to proteinuria and chronic kidney disease in unilateral multicystic dysplastic kidney (MCDK). We aimed to investigate the urine neutrophil-gelatinase-associated lipocalin (NGAL), netrin-1, hepcidin, and C-C motif chemokine ligand-2 (MCP-1/CCL-2) levels in patients with MCDK. Methods: Thirty-two patients and 25 controls were included. The urine hepcidin, netrin-1, NGAL, and MCP-1/CCL-2 levels were determined by ELISA. Results: The patients had higher serum creatinine (Cr) levels, urine albumin, and netrin-1/Cr ratio with lower GFR. There were positive correlations between urine protein/Cr, MCP-1/CCL-2/Cr, and netrin-1 with NGAL (r = 0.397, p = 0.031; r = 0.437, p = 0.041, r = 0.323, p = 0.042, respectively). Urine netrin-1/Cr was positively correlated with MCP-1/CCL-2/Cr (r = 0.356, p = 0.045). There were positive associations between the presence of proteinuria and netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr [Odds ratio (OR): 1.423, p = 0.037, OR: 1.553, p = 0.033, OR: 2.112, p = 0.027, respectively)]. ROC curve analysis showed that netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr had high predictive values for determining proteinuria p = 0.027, p = 0.041, p = 0.035, respectively). Urine hepcidin/Cr was negatively correlated with tubular phosphorus reabsorption and was positively correlated with urine NGAL/Cr (r = -0.418, p = 0.019; r = 0.682, p = 0.000; respectively). Conclusions: MCP-1/CCL-2 may play a role in the development of proteinuria in MCDK. Netrin-1 may be a protective factor against proteinuria-induced renal injury. Urine hepcidin/Cr may reflect proximal tubule damage in MCDK. Urine NGAL/Cr may be a predictor of tubule damage by proteinuria.

Resumo Introdução: A hiperfiltração glomerular pode causar proteinúria e doença renal crônica no rim displásico multicístico unilateral (RDM). Nosso objetivo foi investigar os níveis de lipocalina associada à gelatinase neutrofílica na urina (NGAL), netrina-1, hepcidina e quimiocina C-C com ligante-2 (MCP-1/CCL-2) em pacientes com RDM. Métodos: Trinta e dois pacientes e 25 controles foram incluídos. Os níveis urinários de hepcidina, netrin-1, NGAL e MCP-1/CCL-2 foram determinados por ELISA. Resultados: Os pacientes apresentaram níveis séricos mais elevados de creatinina (Cr), albumina na urina e relação netrina-1/Cr com menor TFG. Houve correlação positiva entre proteína na urina/Cr, MCP-1/CCL-2/Cr e netrina-1 com NGAL (r = 0,397, p = 0,031; r = 0,437, p = 0,041, r = 0,323, p = 0,042, respectivamente). A netrina-1/Cr na urina foi correlacionada positivamente com MCP-1/CCL-2/Cr (r = 0,356, p = 0,045). Houve associações positivas entre a presença de proteinúria e netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr [Odds ratio (OR): 1,423, p = 0,037, OR: 1,553, p = 0,033, OR: 2,112, p = 0,027, respectivamente) ]. A análise da curva ROC mostrou que netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr apresentaram altos valores preditivos para determinar a proteinúria p = 0,027, p = 0,041, p = 0,035, respectivamente). A hepcidina/Cr na urina foi correlacionada negativamente com a reabsorção tubular de fósforo e positivamente com a NGAL/Cr na urina (r = -0,418, p = 0,019; r = 0,682, p = 0,000; respectivamente). Conclusões: MCP-1/CCL-2 pode ter participação no desenvolvimento de proteinúria no RDM. A Netrina-1 pode ser um fator protetor contra lesão renal induzida por proteinúria. Hepcidina/Cr na urina pode refletir danos em túbulos proximais no RDM. O valor de NGAL/Cr urinário pode ser um preditor de danos nos túbulos por proteinúria.

Humans , Female , Multicystic Dysplastic Kidney/metabolism , Biomarkers , Proto-Oncogene Proteins , Chemokines , Creatinine , Hepcidins , Lipocalin-2 , Netrin-1 , Ligands
Rev. Assoc. Med. Bras. (1992) ; 66(3): 300-306, Mar. 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1136211


SUMMARY OBJECTIVES To compare the serum concentrations of adipokines resistin and chemerin in children and adolescents with eutrophic and overweight and to evaluate their relationship with anthropometric, biochemical, and blood pressure variables. METHODS a cross-sectional epidemiological study was conducted with 234 students enrolled in public elementary schools in the city of Juiz de Fora / MG. Anthropometric evaluation, biochemistry, and blood pressure measurement were performed. Statistical analyzes included the Student-t or Mann-Whitney tests, Pearson or Spearman correlation, used according to the distribution of the variables, and linear regression analysis, by means of the evaluation of the effect of the independent variables on the serum levels of chemerin and resistin, adjusted for age and sex. For the data analysis, SPSS® software version 21.0 and STATA® version 10.1 were used, assuming a significance level of 5%. RESULTS the concentrations of chemerin were higher in eutrophic individuals than in those with excess weight (p> 0.05). In contrast, levels of resistin were higher in the young with excess weight than in the eutrophic ones (p <0.05). In the multiple linear regression analysis, the levels of chemerin were associated with the values of resistin, systolic, and diastolic blood pressure. Resistance levels maintained association only with BMI and chemerin values. CONCLUSION the adipokines analyzed presented a distinct profile in the groups of children and adolescents with eutrophic and overweight.

RESUMO OBJETIVOS Comparar as concentrações séricas das adipocinas resistina e quemerina em crianças e adolescentes com eutrofia e excesso de peso e avaliar sua relação com as variáveis antropométricas, bioquímicas e a pressão arterial. MÉTODOS Estudo epidemiológico transversal realizado com 234 estudantes matriculados em escolas públicas do ensino fundamental no município de Juiz de Fora/MG. Realizou-se avaliação antropométrica, bioquímica e aferição da pressão arterial. As análises estatísticas compreenderam os testes t de Student ou Mann-Whitney, correlação de Pearson ou Spearman, utilizados de acordo com a distribuição das variáveis, e análise de regressão linear, realizada por meio da avaliação do efeito das variáveis independentes nos níveis séricos de quemerina e resistina, ajustado por idade e sexo. Para a análise dos dados foram utilizados os softwares SPSS® versão 21.0 e Stata® versão 10.1, admitindo-se nível de significância de 5%. RESULTADOS As concentrações de quemerina foram maiores nos indivíduos eutróficos do que nos com excesso de peso (p>0,05). Em contrapartida, os níveis de resistina estiveram maiores nos jovens com excesso ponderal do que nos eutróficos (p<0,05). Na análise de regressão linear múltipla, os níveis de quemerina apresentaram associação com os valores de resistina, pressão arterial sistólica e diastólica. Os níveis de resistina mantiveram associação apenas com os valores de IMC e quemerina. CONCLUSÃO As adipocinas analisadas apresentaram perfil distinto nos grupos de crianças e adolescentes com eutrofia e com excesso de peso.

Humans , Male , Female , Child , Adolescent , Chemokines/blood , Overweight/blood , Adiponectin/blood , Resistin/blood , Anthropometry , Cross-Sectional Studies , Intercellular Signaling Peptides and Proteins , Overweight/complications , Overweight/metabolism , Adipokines
Article in Chinese | WPRIM | ID: wpr-781695


OBJECTIVE@#To study the changes in the serum levels of Chemerin and Omentin-1 in children with Kawasaki disease (KD) in the acute stage after intravenous immunoglobulin (IVIG) treatment and related clinical significance.@*METHODS@#A total of 60 children who were diagnosed with KD from January 2015 to April 2019 were enrolled as subjects. Forty healthy children and 40 children with acute infectious diseases were enrolled as the healthy control group and the infection control group respectively. According to the sensitivity to IVIG treatment, the children with KD were divided into an IVIG sensitive group with 51 children and a non-IVIG sensitive group with 9 children. According to the presence or absence of coronary artery lesion, the children with KD were divided into a CAL group with 13 children and a non-CAL group with 47 children. ELISA was used to measure the serum levels of Omentin-1 and Chemerin before and after the treatment.@*RESULTS@#The children with KD had significantly higher serum levels of Chemerin and Omentin-1 than the healthy control and infection control groups before treatment (P0.05). Before treatment, the non-IVIG sensitive group had a significantly higher serum level of Chemerin than the IVIG sensitive group (P0.05).@*CONCLUSIONS@#High serum levels of Chemerin and Omentin-1 may play an important role in the development and progression of KD. Chemerin may be involved in the development of CAL in children with KD. The serum level of Chemerin may be used as a new index for predicting the sensitivity to IVIG treatment.

Adipokines , Chemokines , Child , Coronary Artery Disease , Humans , Immunoglobulins, Intravenous , Mucocutaneous Lymph Node Syndrome
Braz. j. med. biol. res ; 53(6): e9113, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132518


Chemerin is an adipokine that has been associated with components of metabolic syndrome. It has been described to affect adipocyte metabolism and inflammatory responses in adipose tissue, as well as the systemic metabolism of lipids and glucose. Few epidemiological studies have evaluated classical and genetics cardiovascular risk factors (CVRFs) in the mixed adult rural population in Brazil. Therefore, the present study explored possible associations between CVRFs and chemerin. This cross-sectional study included 508 adults from the rural localities of Lavras Novas, Chapada, and Santo Antônio do Salto in Ouro Preto, Minas Gerais, Southeast Brazil. Demographic, behavioral, clinical, biochemical, anthropometric variables, and 12 single nucleotide polymorphisms (SNPs) linked with metabolic syndrome phenotypes were evaluated for associations with chemerin level. There was a significant association of high triglyceride levels [odds ratio (OR)=1.91, 95%CI: 1.23−2.98], insulin resistance (OR=1.82, 95%CI: 1.03−3.22), age (OR=1.64, 95%CI: 1.08−2.49), and sex (OR=1.99, 95%CI: 1.35−2.95) with high levels of chemerin. High chemerin levels were significantly associated with the genetic polymorphisms rs693 in the APOB gene (OR=1.50, 95%CI: 1.03−2.19) and rs1799983 in the NOS3 gene (OR=1.46, 95%CI: 1.01−2.12) for the AA and GT+TT genotypes, respectively. In the concomitant presence of genotypes AA of rs693 and GT+TT of rs1799983, the chance of presenting high levels of chemerin showed a 2.21-fold increase (95%CI: 1.25−3.88) compared to the reference genotype. The development of classical CVRFs in this population may be influenced by chemerin and by two risk genotypes characteristic of variants in well-studied genes for hypertension and dyslipidemia.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Apolipoproteins B/genetics , Cardiovascular Diseases/genetics , Chemokines/blood , Polymorphism, Single Nucleotide/genetics , Nitric Oxide Synthase Type III/genetics , Rural Population , Brazil , Cardiovascular Diseases/metabolism , Cross-Sectional Studies , Risk Factors , Chemokines/genetics , Genotype
Article in English | WPRIM | ID: wpr-826302


Methylmercury is an environmental pollutant that causes neurotoxicity. Recent studies have reported that the ubiquitin-proteasome system is involved in defense against methylmercury toxicity through the degradation of proteins synthesizing the pyruvate. Mitochondrial accumulation of pyruvate can enhance methylmercury toxicity. In addition, methylmercury exposure induces several immune-related chemokines, specifically in the brain, and may cause neurotoxicity. This summary highlights several molecular mechanisms of methylmercury-induced neurotoxicity.

Animals , Chemokines , Metabolism , Humans , Methylmercury Compounds , Toxicity , Mice , Neurotoxins , Toxicity , Proteolysis , Rats , Saccharomyces cerevisiae
Rev. saúde pública (Online) ; 53: 35, jan. 2019. tab
Article in English | LILACS | ID: biblio-991637


ABSTRACT OBJECTIVE Analyze whether inflammatory markers are associated with falls among older adults living in Bambuí. METHODS Study that analyzed baseline data from a Bambuí Cohort Study of Aging, involving 1,250 participants. Data about falls were collected from previous 12 months, classified as single or multiple occurrence and severity (participant seeking health services). Information about sociodemographic characteristics, health behaviors and health condition was also collected and used as confounding factors. The exposures of interest included interleukins (IL-1β, IL-6, IL-8, IL-10, IL-12), tumor necrosis factor (TNF), ultra-sensitive C-reactive protein (us-CRP) and chemokines (CXCL9, CCL5, CCL10, MCP1). Data were processed through logistic regression, obtaining odds ratio and 95% confidence interval (95%CI). RESULTS The prevalence of falls was 27.1%; 40.1% of the older adults reported multiple falls and 33.3% sought health services. After adjustments, the following elevated levels were associated with falls: us-CRP (OR = 1.46, 95%CI 1.04-2.03), CCL5 (OR = 1.38, 95%CI 1.01-1.90) and CXCL9 (OR = 1.43, 95%CI 1.02-2.02). An association was observed between the number of elevated markers and the occurrence of falls: two (OR = 1.47, 95%CI 1.02-2.12) and three (OR = 2.08, 95%CI 1.12-3.87) elevated biomarkers indicated fall probability of 32.0% and 39.4%, respectively. CONCLUSIONS Elevated levels of us-CRP, CCL5 and CXCL9, which were associated with falls, may contribute to a proper understanding of the mechanism associated with the occurrence of falls among older people.

RESUMO OBJETIVO Analisar se marcadores inflamatórios estão associados a quedas em idosos vivendo na comunidade. MÉTODOS Estudo da coorte de idosos de Bambuí, envolvendo 1.250 participantes da linha de base do projeto. Foram coletadas informações sobre quedas nos últimos 12 meses, classificadas quanto à ocorrência (única ou múltipla) e gravidade (procura por serviços de saúde). O inquérito também continha informações a respeito das características sociodemográficas, comportamentais e condições de saúde, as quais foram utilizadas como fatores de confusão. As exposições pesquisadas incluíram: interleucinas (IL-1β, IL-6, IL-8, IL-10 e IL-12), fator de necrose tumoral (TNF), proteína C reativa ultrassensível (PCRus) e quimiocinas (CXCL9, CCL5, CCL10 e MCP1). O tratamento dos dados foi realizado por meio de regressão logística, obtendo-se odds ratio e intervalo de 95% de confiança (IC95%). RESULTADOS A prevalência de queda foi 27,1%; 40,1% dos idosos relataram quedas múltiplas e 33,3% procuraram serviços de saúde. Após ajustes, permaneceram associados às quedas os níveis elevados de PCRus (OR = 1,46; IC95% 1,04-2,03), CCL5 (OR = 1,38; IC95% 1,01-1,90) e CXCL9 (OR = 1,43; IC95% 1,02-2,02). Houve associação entre o número de marcadores elevados e a ocorrência de quedas: dois (OR = 1,47; IC95% 1,02-2,12) e três (OR = 2,08; IC95% 1,12-3,87) biomarcadores aumentados predisseram probabilidades de quedas iguais a 32,0% e 39,4%, respectivamente. CONCLUSÕES Os níveis elevados de PCRus, CCL5 e CXCL9, que estiveram associados a quedas, podem contribuir para o adequado entendimento do mecanismo associado à ocorrência desse evento em idosos.

Humans , Male , Female , Aged , Accidental Falls , Aging , Interleukins/blood , Tumor Necrosis Factor-alpha/blood , Chemokines/blood , Brazil , Biomarkers/blood , Body Mass Index , Polymerase Chain Reaction , Nutritional Status , Prospective Studies , Risk Factors , Educational Status , Middle Aged
Belo Horizonte; s.n; 2019. 55 p. ilus, tab.
Thesis in English, Portuguese | LILACS, BBO | ID: biblio-1102438


O tratamento endodôntico tem como objetivo eliminar a contaminação microbiana dos sistemas de canais radiculares (SCR) por meio da instrumentação mecânica e irrigação química (PMQ). Quando não for possível a resolução em uma única sessão, o SCR deverá ser preenchido com uma medicação intracanal para evitar a recolonização microbiana tardia. O presente estudo teve como objetivo avaliar a ação do hidróxido de cálcio, mundialmente utilizado como medicação intracanal, associado ao selênio (H.C + Se), em dentes portadores de necrose pulpar. A amostra foi composta por 60 pacientes que possuiam dentes com indicação de tratamento endodôntico, divididos em grupos (n=15): sem medicação intracanal (Empty); que foram medicados com hidróxido de cálcio (H.C), Selênio (Se) e hidróxido de cálcio + selênio (H.C + Se). Após a abertura coronária, 3 cones de papel absorvente foram inseridos no terço inicial do conduto e mantidos por 2 min para avaliação microbiana. Após o PMQ, novos cones foram introduzidos nos SCR, ultrapassando-se 2mm do ápice radicular, e mantidos no tecido perirradicular por 2min para a coleta do fluido intersticial periapical. A coleta foi novamente realizada 15 dias após o PMQ. A expressão gênica do mRNA do fragmento 16S de procariontes, das citocinas INF-γ, TNF-α, IL-1α, IL-17A, IL-10, IL-6 e MCP-1 foram quantificadas por PCR em tempo real. O mRNA 16S foi avaliado antes do PMQ e 15 dias após, nos grupos sem medicação e com medicação intracanal. A redução significativa da carga microbiana foi observada apenas no grupo com medicação intracanal (p<0,05). Observou-se um aumento da expressão gênica das citocinas (T15) TNF-α e IL-10 no grupo H.C+Se em comparação aos demais grupos (p<0,05). A expressão de mRNA de IFN-γ reduziu nos grupos tratados com as medicações (H.C, Se, H.C + Se). Conclui-se que o uso de medicação intracanal é imprescindível para se evitar a recolonização do SCR. A inclusão do selênio na pasta de hidróxido de cálcio resultou na potencialização da expressão de citocinas que permitirão o reparo dos tecidos perirradiculares.

Endodontic treatment aims to eliminate the microbial contamination of the root canal system (RCS) and is achieved with the use of mechanical instrumentation and chemical irrigation. When resolution in a single session is not possible, the RCS should be filled with intracanal medication to avoid subsequent recolonization. The present study aimed to evaluate the effect of calcium hydroxide, wich is used globally as an intracanal medication, in combination with selenium (CH + Se) as an intracanal medication in teeth with pulp necrosis. The sample consisted of 60 patients requiring endodontic treatment who were divided into groups: without intracanal medication (empty) and with medication; calcium hydroxide (CH), selenium (Se) and calcium hydroxide + selenium (CH + Se) (n = 15). After the coronary opening, three absorbent paper cones were inserted in the initial third of the RCS and maintained for 2min for microbial evaluation. After the cleaning and shaping procedures, new cones were introduced into the RCS, extending 2 mm from the root apex and were kept in the periradicular tissue for 2 min' to collect the periapical fluid. The collection was also performed 15 days later. Real time PCR was used to quantify the expression of the prokaryotic 16S ribosomal RNA gene. Additionally, the cytokines IFN-γ, TNF-α, IL-1α, IL-17A, IL-10, IL-6 and MCP-1 were also quantified by real-time PCR. The 16S mRNA was evaluated before the cleaning and shaping procedures and 15 days later in the groups treated with or without medication. A significant reduction in the microbial load was observed only in the intracanal group (p <0.05). There was an increase in the gene expression level of the cytokines (T15) TNF-α and IL-10 in the CH+ group compared to the other groups (p <0.05). The expression of IFN-γ mRNA was reduced in the groups treated with the medications (CH, Se, and CH + Se). The findings of the present study indicate that in the case of treatment over multiple sessions, the use of intracanal medication is essential to avoid the recolonization of the RCS. The inclusion of selenium with calcium hydroxide resulted in the potentiation of the anti-inflammatory phase of the periradicular tissues.

Root Canal Therapy , Selenium , Calcium Hydroxide , RNA, Ribosomal, 16S , Gene Expression , Cytokines , Chemokines , Root Canal Irrigants
Cad. Saúde Pública (Online) ; 35(3): e00129918, 2019. tab
Article in Portuguese | LILACS | ID: biblio-989524


O objetivo do trabalho foi identificar os pontos de corte dos marcadores inflamatórios que melhor discriminassem a ocorrência da síndrome metabólica entre idosos residentes na comunidade. Foram utilizados os dados da linha de base da coorte de idosos conduzida na cidade de Bambuí, Minas Gerais, Brasil. A exposição de interesse foi a presença da síndrome metabólica, definida pelo critério Adult Treatment Panel III, e os desfechos incluíram os seguintes marcadores inflamatórios: citocinas (IL-1β, IL-6, IL-10, IL-12 e TNF), quimiocinas (CXCL8, CXCL9, CCL2, CXCL10 e CCL5) e proteína C-reativa (PCR). A definição dos pontos de corte dos marcadores inflamatórios foi baseada no método Classification and Regression Tree (CART). As associações entre esses marcadores e a síndrome metabólica foram estimadas por modelos de regressão logística, obtendo-se odds ratio e intervalos de 95% de confiança (IC95%), considerando o ajustamento por fatores de confusão. A prevalência da síndrome metabólica foi de 49,1%, e os níveis de IL-1β, IL-12 e TNF não se mostraram associados a essa exposição. Após ajustamento, a presença da síndrome metabólica foi associada a maiores valores de IL-6 e PCR e a menores valores de CXCL8 e CCL5. Associações significativas ainda foram observadas com níveis séricos intermediários de CXCL9 e CXCL10. Além disso, a combinação dos marcadores apresentou associação significativa e consistente com a síndrome metabólica. Além de demonstrar associação entre síndrome metabólica e uma ampla gama de biomarcadores, alguns ainda não descritos na literatura, os resultados ressaltam que essa associação ocorre em níveis muito inferiores aos já demonstrados, sugerindo que a síndrome metabólica desempenha importante papel no perfil inflamatório dos idosos.

El objetivo del trabajo fue identificar los puntos de corte de los marcadores inflamatorios que mejor discriminaran la ocurrencia del síndrome metabólico entre ancianos residentes en comunidades. Se utilizaron datos de referencia de una cohorte de ancianos, realizada en la ciudad de Bambuí, Minas Gerais, Brasil. La exposición de interés fue la presencia del síndrome metabólico, definida por el criterio Adult Treatment Panel III, y los desenlaces incluyeron los siguientes marcadores inflamatorios: citocinas (IL-1β, IL-6, IL-10, IL-12 e TNF), quimiocinas (CXCL8, CXCL9, CCL2, CXCL10 y CCL5) y proteína C-reactiva (PCR). La definición de los puntos de corte de los marcadores inflamatorios se basó en el método Classification and Regression Tree (CART). Las asociaciones entre esos marcadores y el síndrome metabólico se estimaron mediante modelos de regresión logística, obteniéndose odds ratio e intervalos con 95% de confianza, considerando el ajuste por factores de confusión. La prevalencia del síndrome metabólico fue de 49,1%, y los niveles de IL-1β, IL12 y TNF no se mostraron asociados a esa exposición. Tras el ajuste, la presencia del síndrome metabólico se asoció a mayores valores de IL-6 y PCR y a menores valores de CXCL8 y CCL5. Las asociaciones significativas se observaron incluso con niveles séricos intermedios de CXCL9 y CXCL10. Asimismo, la combinación de los marcadores presentó una asociación significativa y consistente con el síndrome metabólico. Además de demostrar asociación entre el síndrome metabólico y una amplia gama de biomarcadores, algunos todavía no descritos en la literatura, los resultados resaltan que esa asociación ocurre en niveles muy inferiores a los ya demostrados, sugiriendo que el síndrome metabólico desempeña un importante papel en el perfil inflamatorio de los ancianos.

The study aimed to identify the cutoff points for inflammatory markers that best discriminate the occurrence of metabolic syndrome in community-dwelling older adults. Baseline data were used from the elderly cohort in the city of Bambuí, Minas Gerais State, Brazil. The target exposure was presence of metabolic syndrome, defined according to the Adult Treatment Panel III criterion, and the outcomes included the following inflammatory markers: cytokines (IL-1β, IL-6, IL-10, IL-12 e TNF), chemokines (CXCL8, CXCL9, CCL2, CXCL10, and CCL5), and C-reactive protein (CRP). Definition of the cutoff points for the inflammatory markers was based on the Classification and Regression Tree (CART) method. The associations between these markers and metabolic syndrome were estimated by logistic regression models, obtaining odds ratios and 95% confidence intervals, considering adjustment for confounding factors. Prevalence of metabolic syndrome was 49.1%, and IL-1β, IL-12, and TNF levels were not associated statistically with this exposure. After adjustment, presence of metabolic syndrome was associated with higher IL-6 and CRP levels and lower CXCL8 and CCL5. Significant associations were also observed with intermediate serum CXCL9 and CXCL10 levels. The combination of markers also showed a significant and consistent association with metabolic syndrome. In addition to demonstrating an association between metabolic syndrome and a wide range of biomarkers (some not previously described in the literature), the results highlight that this association occurs at much lower levels than previously demonstrated, suggesting that metabolic syndrome plays an important role in the inflammatory profile of the older adults.

Humans , Male , Female , Middle Aged , Aged , Biomarkers/blood , Chemokines/blood , Metabolic Syndrome/diagnosis , Brazil , C-Reactive Protein , Prospective Studies , Chemokines/classification , Inflammation/blood
Rio de Janeiro; s.n; 2019. 110 p. ilus.
Thesis in Portuguese | LILACS | ID: biblio-1178153


Dengue é uma doença causada pelo vírus dengue (DENV) com amplo espectro clínico, variando desde uma infecção assintomática a casos graves, com manifestações hemorrágicas e/ou extravasamento plasmático, que podem levar o paciente ao óbito. Durante a infecção, mediadores pró-inflamatórios, como citocinas e quimiocinas, apresentam papel chave na imunopatogênese da dengue. Dentre esses mediadores, as quimiocinas exercem influência em diversos processos homeostáticos e inflamatórios, atuando na ativação do endotélio vascular e na migração celular. O objetivo desse trabalho foi avaliar a influência das quimiocinas CCL5, CX3CL1 e CXCL10 na alteração da permeabilidade endotelial e na migração de linfócitos T em pacientes infectados com DENV. Soro e células mononucleares do sangue periférico (do inglês PBMC) dos pacientes foram utilizados neste estudo, e obtidas durante as epidemias de 2013 e 2016.

Após a confirmação do diagnóstico laboratorial para dengue, os pacientes foram classificados clinicamente segundo critérios da OMS 2009. Níveis séricos das citocinas TNF-α, IL-1ß e IL-10 e quimiocinas CCL2, CCL5, CXCL8, CXCL10 e CX3CL1 de pacientes foram quantificadas por ELISA e LUMINEX. Para avaliação da permeabilidade endotelial in vitro foi realizado medida da resistência elétrica transendotelial (TEER) em HMVEC-d, através do equipamento Milicell-ERS acoplada a câmara Endohm 6, na presença de soro pré-tratados ou não com anticorpos neutralizantes anti-CCL5, anti-CXCL10 ou anti-CX3CL1. A caracterização do perfil de expressão dos receptores de quimiocinas CCR4, CCR5, CCR7 e CX3CR1 em linfócitos T de pacientes e controles sadios foram realizados por citometria de fluxo. Para avaliação da capacidade in vitro de migração de linfócitos T em câmara transwell foram utilizados os recombinantes TNF+CXCL8/IL-8, CCL5 ou CX3CL1.

Os resultados demonstraram a influência de constituintes presentes no soro de pacientes na alteração da permeabilidade da monocamada de células endoteliais. Essa alteração foi observada com mais frequência nos casos FDSA/Grave comparado aos casos FD e controles sadios. Dentre os mediadores próinflamatórios quantificados, os níveis de CCL5 foram menores em pacientes cujo soro foi capaz de induzir alteração da permeabilidade das HMVEC-d, comparado aos pacientes cujo soro não induziu. O pré-tratamento do soro de pacientes que promoveram a redução do TEER relativo com os anticorpos bloqueadores CCL5 e CX3CL1, levou ao aumento do valor TEER relativo das células HMVEC-d, indicando que, neste grupo de pacientes, existe uma influência das quimiocinas CCL5 e CX3CL1 na manutenção da integridade endotelial. Pacientes FDSA/Grave apresentam maior frequência de linfócitos T CD4 e CD8 expressando CCR5 e CX3CR1 em comparação aos linfócitos T de pacientes FD. Estudo sobre a influência das quimiocinas CCL5 e CX3CL1 na migração de linfócitos T de pacientes indicou que tanto os linfócitos T CD4 como os CD8 de pacientes FDSA/Grave migram mais, independente da presença do estímulo quimiotático, do que os linfócitos T de pacientes FD, provavelmente porque as células dos FDSA/Grave expressam mais a molécula CD49d. Em condições nas quais foram utilizados os recombinantes CCL5 e CX3CL1 como estímulos quimiotáticos, os linfócitos T CD4 e CD8 de pacientes FDSA/Grave foram mais responsivos ao CCL5 e, portanto, migraram mais na presença de CCL5, comparado aos linfócitos T dos pacientes FD. O conjunto desses dados demonstra a influência das quimiocinas CCL5 e CX3CL1 na regulação da integridade endotelial e de CCL5 na migração dos linfócitos T, mais evidenciado nos pacientes FDSA/Grave. (AU)

Humans , Permeability , Cell Movement , Chemokines , Dengue , Endothelial Cells
São Paulo; s.n; 2019. 110 p. ilust, tabelas, quadros.
Thesis in Portuguese | LILACS, Inca | ID: biblio-1179935


Introdução: O melanoma cutâneo é uma neoplasia maligna dos melanócitos da pele com incidência variável no mundo e o prognóstico é desfavorável nos estágios mais avançados. O desenvolvimento do melanoma está associado ao sistema imunológico e a maior evolução no seu tratamento se deu a partir de medicamentos baseados no estímulo da resposta imune contra o tumor. Objetivo: Avaliar a expressão de citocinas e quimiocinas, dos agregados de plaquetas-leucócitos e de mediadores solúveis sCD40L e sCD62P no sangue de pacientes com melanoma cutâneo. Métodos: Foi realizado um estudo transversal em pacientes com melanoma cutâneo admitidos para tratamento cirúrgico no Hospital de Câncer de Pernambuco (HCP), entre os anos de 2015 e 2018. Foram incluídos 51 pacientes (média de 57,6 anos) com diagnóstico de melanoma cutâneo, e como grupo controle, 30 indivíduos saudáveis (média de 56,7 anos). As coletas de sangue foram realizadas antes da ressecção do melanoma. A determinação dos níveis de citocinas IL6, IL10, TNF, IL1 e IL12p70 e das quimiocinas CXCL10 (IP10), CCL2 (MCP-1), CXCL9 (MIG), CCL5 (RANTES) e CXCL8 (IL8), sCD40L e sCD62P, e agregados plaquetas-leucócitos foi realizada por citometria de fluxo. Foram realizadas análises entre os grupos de pacientes e controles, e pelos parâmetros como tipo histológico, estadio, espessura de Breslow e presença de metástases linfonodais. O teste de Mann-Whitney foi utilizado para comparação entre dois grupos, e de Kruskal-Wallis para as análises entre três ou mais grupos. Foi considerado significativo p<0,05. Resultados: Não houve detecção de IL1 e IL12 no sangue dos pacientes e controles. Verificou-se níveis elevados das citocinas IL10 e diminuídos de TNF nos pacientes comparados ao grupo controle, (p<0,0001). A IL6 esteve aumentada nos pacientes com estadio II em relação ao III (p=0,017) e em pacientes com linfonodos negativos (p<0,0001). Foram encontrados níveis reduzidos da quimiocina CCL5 (p=0,009) nos pacientes quando comparados ao grupo controle. O percentual de agregação plaquetária em linfócitos, monócitos e neutrófilos também foi elevado nos pacientes comparado ao grupo controle (p<0,0001, p=0,009 e p<0,0001 respectivamente). Foram encontrados níveis elevados de agregados plaquetas-monócitos nos pacientes com linfonodos positivos (p=0,008). Os níveis solúveis sCD40L e sCD62P foram elevados nos pacientes comparados aos controles (p=0,03 e p=0,006, respectivamente). Conclusão: Os dados obtidos das análises realizadas mostram que os pacientes com melanoma cutâneo apresentam um perfil imunossupressor com a participação de plaquetas e monócitos/macrófagos que favorecem a progressão tumoral

Cutaneous melanoma is a malignancy originated from the skin melanocytes, with a variable incidence worldwide and a poor prognosis in advanced stages. Melanoma growth is closely associated with the immune system and the most important treatment advances resulted from stimulation of immune response against the tumor. Objective: To evaluate the expression of cytokines and chemokines, platelet-leukocyte aggregates and soluble mediators sCD40L and sCD62P in the blood of patients with cutaneous melanoma. Methods: A cross-sectional study was performed in cutaneous melanoma patients admitted for surgical treatment at the Hospital de Câncer de Pernambuco (HCP) between 2015 and 2018. Fifty-one patients (mean age 57.6 years) with a diagnosis of melanoma were included, and 30 healthy individuals (mean age 56.7 years) were chosen as the control group. The blood samples were taken before resection of the melanoma. The determination of cytokines IL6, IL10, TNFα, IL1ß and IL12p70 and chemokines CXCL10 (IP10), CCL2 (MCP-1), CXCL9 (MIG), CCL5 (RANTES) and CXCL8 (IL8), sCD40L and sCD62P, and platelet-leukocyte aggregate was performed by flow cytometry. Analysis were performed between patient and control groups, and by parameters such as histological type, stage, Breslow thickness, and presence of lymph node metastases. Mann-Whitney test was used for comparison between the two groups, and Kruskal-Wallis test for analysis between three or more groups. It was considered significant p <0.05. Results: There was no detection of IL1ß and IL12 in the blood of patients and controls. Elevated levels of IL10 and decreased TNFα cytokines were found in patients compared to the control group (p <0.0001). IL6 was increased in patients with stage II compared to III (p=0.017) and in patients with negative lymph nodes (p <0.0001). Reduced CCL5 chemokine levels (p=0.009) were found in patients compared to the control group. The percentage of platelet aggregation in lymphocytes, monocytes and neutrophils was also high in patients when compared to the control group (p <0.05). High levels of platelet-monocyte aggregates were found in patients with positive lymph nodes (p=0.008). Soluble sCD40L and sCD62P levels were elevated in patients compared to controls (p=0.03 and p=0.006, respectively). Conclusion: The data obtained from the analysis performed show that patients with cutaneous melanoma have an immunosuppressive profile with platelet participation and monocytes/macrophages that favor tumor progression

Humans , Male , Female , Adult , Middle Aged , Aged , Platelet Aggregation , Cytokines , P-Selectin , Chemokines , CD40 Ligand , Melanoma
Immune Network ; : e22-2019.
Article in English | WPRIM | ID: wpr-764009


Ovarian cancer (OC), the deadliest gynecological cancer, results in poor overall survival, urgently requiring a novel therapeutic approach. As cumulative exposures to endotoxins decreased OC risk epidemiologically, we evaluated if LPS, a Toll-like receptor 4 agonist known as active component of endotoxins, could increase survival in the murine peritoneal dissemination model of SKOV-3 OC cells. LPS significantly increased the mean survival time of more than 116 days compared with 63 days in the control. Furthermore, no tumor burden was present in three mice among eight LPS-treated mice. SKOV-3 cells were not responsive to LPS and showed unaltered chemokine signature. Rather than direct effects to OC cells, LPS was found to increase proinflammatory chemokines and cytokines, such as CXCL1, CXCL8, TNF, and IL-1B, in innate immune system. Taken together, LPS is likely to potentiate the cytotoxic-related innate immunogenicity via proinflammatory chemokines and cytokines, which attenuates the peritoneal dissemination of OC.

Animals , Chemokines , Cytokines , Endotoxins , Immune System , Immunity, Innate , Lipopolysaccharides , Mice , Ovarian Neoplasms , Survival Rate , Toll-Like Receptor 4 , Tumor Burden
Article in English | WPRIM | ID: wpr-773985


Atopic dermatitis (AD) is among the most common skin disorders in humans. Although a variety of regimens are available for the treatment of AD, preventive approaches are limited. Recent studies have demonstrated that certain naturally-occurring herbal medicines are effective in preventing the development of AD via divergent mechanisms, such as inhibiting cytokine and chemokine expression, IgE production, inflammatory cell infiltration, histamine release, and/or enhancement of epidermal permeability barrier function. Yet, they exhibit few adverse effects. Since herbal medicines are widely available, inexpensive and generally safe, they could represent an ideal approach for preventing the development of AD, in both highly developed and developing countries.

Animals , Chemokines , Metabolism , Dermatitis, Atopic , Disease Models, Animal , Herbal Medicine , Humans , Immunoglobulin E , Metabolism , Inflammation , Pathology