Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 12.433
Filtrar
1.
Medicine (Baltimore) ; 98(39): e17373, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574886

RESUMO

Ionizing radiation can induce deoxyribonucleic acid (DNA) methylation pattern change, and ionizing radiation-induced oxidative damage may also affect DNA methylation status. However, the influence of low-dose ionizing radiation, such as occupational radiation exposure, on DNA methylation is still controversial.By investigating the relationship between occupational radiation exposure and DNA methylation changes, we evaluated whether radiation-induced oxidative damage was related to DNA methylation alterations and then determined the relationship among occupational radiation level, DNA methylation status, and oxidative damage in interventional physicians.The study population included 117 interventional physicians and 117 controls. We measured global methylation levels of peripheral blood leukocyte DNA and expression level of DNA methyltransferase (Dnmts) and homocysteine (Hcy) in serum to assess the DNA methylation status of the body. We measured 8-hydroxy-2'-deoxyguanosine (8-OHDG) and 4-hydroxynonenal (4-HNE) levels as indices of oxidative damage. Relevance analysis between multiple indices can reflect the relationship among occupational radiation exposure, DNA methylation changes, and oxidative damage in interventional physicians.The expression levels of Dnmts, 4-HNE, and 8-OHDG in interventional physicians were higher than those in controls, while there was no statistical difference in total DNA methylation rate and expression of Hcy between interventional physicians and controls. Total cumulative personal dose equivalent in interventional physicians was positively correlated with the expression levels of Dnmts, 8-OHDG, and 4-HNE. The expression levels of 8-OHDG in interventional physicians were negatively correlated with global DNA methylation levels and positively correlated with the expression levels of Hcy.Occupational radiation exposure of interventional physicians has a certain effect on the expression of related enzymes in the process of DNA methylation, while ionizing radiation-induced oxidative damage also has a certain effect on DNA methylation. However, there was no evidence that dose burden of occupational exposure was associated to changes of DNA methylation status of interventional physicians, since it is rather unclear which differences are observed among the effects produced by radiation exposure and oxidative damage.


Assuntos
Dano ao DNA/efeitos da radiação , Metilação de DNA/efeitos da radiação , Exposição Ocupacional/análise , Estresse Oxidativo/efeitos da radiação , Exposição à Radiação/análise , Radiologia Intervencionista/estatística & dados numéricos , Adulto , Aldeídos/sangue , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Feminino , Homocisteína/sangue , Humanos , Leucócitos/metabolismo , Masculino , Metiltransferases/sangue , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Médicos/estatística & dados numéricos , Exposição à Radiação/efeitos adversos
2.
Adv Gerontol ; 32(3): 422-430, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31512430

RESUMO

We used quantitative real-time PCR method to analyse mtDNA copy number in a random subsample (n=996; 358 men aged 66,31±7,24 years; 468 women aged 67,62±7,1 years) selected from a population cohort (n=9 630) examined at baseline in international project HAPIEE in Novosibirsk, Russia, in 2003-2005. The participants were re-examined after 12 years in 2015-2017. The average relative number of mtDNA copies in peripheral blood leukocytes was greater in women than in men, independently of age and smoking (p=0,001). mtDNA copy number was inversely correlated with age both in men (p=0,005) and women (p<0,001). In age adjusted analysis, mtDNA copy number was inversely associated with waist, hip and heart rate in both sexes. In addition, mtDNA copy number in women was inversely associated with triglycerides and glucose, aterogenity index and positively with HDL cholesterol. In men, mtDNA copy number was positively associated with physical activity. The age-adjusted mean of mtDNA copy number among male never-smokers was greater than in smokers (p=0,003), and the mean mtDNA copy number was lower in women with diabetes than in women without diabetes (p=0,005). In both sexes, subjects with baseline history of hypertension had lower mtDNA copy number after 12-year follow-up than those without hypertension (p=0,05). This broadly supports the hypothesis that mtDNA copy number may act as biomarker of ageing.


Assuntos
Envelhecimento , Biomarcadores , Variações do Número de Cópias de DNA , DNA Mitocondrial , Diagnóstico , Leucócitos , Idoso , Envelhecimento/genética , Biomarcadores/análise , Feminino , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Federação Russa , Fatores Sexuais
3.
Gene ; 715: 144027, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31374327

RESUMO

OBJECTIVES: To explore the clinical and molecular characteristics of a Chinese Zhuang minority patient with leukocyte adhesion deficiency type-1 (LAD-1) and glucose-6-phosphate dehydrogenase deficiency (G6PDD). METHODS: Routine clinical and physical examinations were performed, and patient data was collected and analyzed. Protein expression levels of Itgb2 and glucose-6-phosphate dehydrogenase (G6pd) proteins were assessed by flow cytometry and the glucose-6-phosphate (G6P) substrate method, respectively. Whole exome sequencing was performed to investigate genetic variations of the patient and his parents. RESULTS: The patient had fester disease and delayed separation of the umbilical cord at birth. Staphylococcus was detected in the fluid secretion of the auditory meatus of the patient. He exhibited a recurrent cheek scab, swollen hand, and swollen gum. Hematological examination indicated dramatic elevation of leukocytes including lymphocytes, monocytes, neutrophils and eosinophils. A novel homozygous mutation was detected in the ITGB2 gene of the patient, which was determined to be a two nucleotide deletion at the site of c.1537-1538 (c.1537-1538delGT), causing a frameshift of 24 amino acids from p.513 and inducing a stop codon (p.V513Lfs*24). A base substitution mutation was identified at c.1466 (c.1466G>T) of G6PD on chromosome X of the patient, which resulted in an amino acid change from arginine to leucine at p.489 (p.R489L). The patient also showed deficient lymphocyte expression of CD18 (2.99%) and significant downregulation of the G6pd protein. CONCLUSIONS: The patient was diagnosed with G6PDD and moderate LAD-1. The combination of LAD-1 and G6PDD in this case may have been due to the high incidence of genetic disease in this minority ethnic population. Analyzing existing LAD-1 and G6PDD cases from different populations can facilitate disease diagnosis and treatment. Particularly, reporting pathogenic mutations of LAD-1 and G6PDD will be crucial for genetic testing and prenatal diagnosis in an effort to decrease the incidence of these diseases.


Assuntos
Antígenos CD18/genética , Deficiência de Glucosefosfato Desidrogenase/genética , Homozigoto , Síndrome da Aderência Leucocítica Deficitária/genética , Mutação de Sentido Incorreto , Substituição de Aminoácidos , Grupo com Ancestrais do Continente Asiático , Antígenos CD18/metabolismo , Deficiência de Glucosefosfato Desidrogenase/patologia , Humanos , Lactente , Síndrome da Aderência Leucocítica Deficitária/metabolismo , Síndrome da Aderência Leucocítica Deficitária/patologia , Leucócitos/metabolismo , Leucócitos/patologia , Masculino
4.
Biomed Environ Sci ; 32(7): 508-519, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31331435

RESUMO

OBJECTIVE: The aim of this study is to investigate the effects of oral cadmium (Cd) ingestion on the pulmonary immune response. METHODS: Determination of Cd content in lungs and histopathological evaluation of the tissue was performed in rats following 30-day oral Cd administration (5 and 50 mg/L). Antioxidant enzyme defense (superoxide dismutase and catalase), cell infiltration, and production of tumor necrosis factor (TNF) and interferon (IFN)-γ, as well as the activity of myeloperoxidase (MPO), nitric oxide (NO), and various cytokines [interleukin (IL)-1ß, IL-6, IL-10, and IL-17] were investigated. RESULTS: Cd caused tissue damage and cell infiltration in the lungs, and this damage was more pronounced at higher doses. Cd deposition resulted in lung inflammation characterized by a dose-dependent IL-1ß increase in lung homogenates, increased TNF levels at both doses, and IL-6 stimulation at low doses with inhibition observed at higher doses. Cd exerted differential effects on lung leukocytes isolated by enzyme digestion, and these effects were characterized by a lack of change in the production of reactive oxygen and nitrogen species, an inhibition of IL-1ß and TNF, and stimulation of MPO and IFN-γ. The higher capacity of Cd-exposed lung cells to respond to the opportunistic pathogen Staphylococcus epidermidis was demonstrated in vitro. CONCLUSION: The potential of ingested Cd to exert both proinflammatory and immunosuppressive effects on pulmonary tissue inflammation and immune reactivity highlights the complex immunomodulatory actions of this metal.


Assuntos
Cádmio/toxicidade , Pulmão/efeitos dos fármacos , Administração Oral , Animais , Cádmio/administração & dosagem , Leucócitos/metabolismo , Pulmão/imunologia , Pulmão/patologia , Masculino , Ratos , Staphylococcus epidermidis , Testes de Toxicidade Subcrônica
5.
Aquat Toxicol ; 213: 105223, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31207538

RESUMO

Methylmercury (MeHg), cadmium (Cd) and arsenic (As(III)) are among the most toxic metals in aquatic systems that have been associated with multiple animal and human health problems. This study investigated cytotoxic, oxidative stress, and apoptosis effects on fish leukocytes following their exposure to metals. A preliminary study indicated that leukocytes exposed to MeHg at a concentration of 0.01 mM, Cd at 0.05 mM, and As(III) at 2 mM showed a time-dependent cell viability reduction (around 40%), so they were selected for further experiments. To evaluate the effect of MeHg, Cd and As(III) on Pacific red snapper Lutjanus peru, we measured cytotoxicity, reactive oxygen species, antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT)), nitric oxide production, apoptosis-related and immune-related genes on head-kidney and spleen leukocytes following exposure to MeHg (0.01 mM), Cd (0.05 mM) and As(III) (2 mM) for 30 min and 2 h. Reactive oxygen species (ROS) generation highly increased in time-dependent doses in head-kidney leukocytes compared with the control group. Regarding antioxidant activity, SOD increased significantly in leukocytes exposed to any heavy metals after two h. Expressly, CAT activity decreased in those leukocytes exposed to Cd and As(III). Apoptotic function genes (Casp-2, Casp-3, and Casp-7) strongly up-regulated after heavy metal exposure, but Cd was more toxic. Finally, granzyme A and perforin 1 strongly up-regulated in leukocytes exposed to MeHg and As(III) compared with the control group. Our data showed that MeHg, Cd, and As(III) might have been cytotoxic and induced oxidative stress and apoptosis with possible biological consequences in fish.


Assuntos
Apoptose/efeitos dos fármacos , Arsênico/toxicidade , Cádmio/toxicidade , Leucócitos/metabolismo , Compostos de Metilmercúrio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Perciformes/metabolismo , Testes de Toxicidade , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Morte Celular/efeitos dos fármacos , Perfilação da Expressão Gênica , Granzimas/metabolismo , Leucócitos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Óxido Nítrico/biossíntese , Perforina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/toxicidade
6.
Clin Ter ; 170(3): e206-e210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31173051

RESUMO

High levels of chemokine (C-X-C motif) receptor (CXCR)3 and monokine induced by interferon (IFN)-γ (MIG) expression were revealed in the intestinal mucosa of mice with experimental colitis, and in lymphocytes, macrophages and epithelial cells of patients with Crohn's disease (CD). CXCR3 and its chemokines expression were induced by IFN-γ in epithelial intestinal cells. These chemokines are involved in the recruitment of granulocytes and mononuclear cells, therefore in the maintenance of inflammation in CD. Serum MIG levels reflect CD disease activity, and it could be a marker for the responsiveness of patients to treatments. Efforts have been made to block MIG or CXCR3 in CD as a potential therapy of CD.


Assuntos
Quimiocina CXCL9/sangue , Doença de Crohn/patologia , Receptores CXCR3/metabolismo , Animais , Biomarcadores/metabolismo , Quimiocinas/metabolismo , Doença de Crohn/metabolismo , Células Epiteliais/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Leucócitos/metabolismo , Linfócitos/metabolismo , Camundongos
7.
Food Chem Toxicol ; 131: 110596, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226429

RESUMO

This study investigated the effects of chlorpyrifos (CPF) on immune-cell populations and intestinal inflammation using a mouse model of inflammatory bowel disease induced by dextran sulfate sodium (DSS). C57BL/6 mice were randomly assigned to five groups with one normal control (NC) and four DSS-treated groups. Mice in the NC group were given distilled water, whereas the DSS-treated groups received distilled water containing 3% DSS for 6 days to induce colitis. The NC and disease control (DC) groups were fed a control semipurified diet, while the remaining groups were exposed to CPF in the AIN-93 diet at doses of 1, 2.5, or 5 mg/kg/day throughout the study. Results showed that dietary exposure to CPF in colitic mice significantly increased circulating classical monocytes and upregulated gene expressions of chemokines in the colon compared to the NC group. Meanwhile, CPF exposure groups had lower plasma cholinesterase activities and higher percentages of circulating neutrophils than those of the DC group. A shorten length, tissue edema, and lipid peroxidation of the colon were also observed in all CPF-exposed mice. These findings suggest that dietary exposure to CPF affected immune-cell populations and inflammatory responses, which led to more severe tissue injury in mice with DSS-induced colitis.


Assuntos
Clorpirifos/toxicidade , Colite/imunologia , Leucócitos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Colo/metabolismo , Colo/patologia , Sulfato de Dextrana , Exposição Dietética , Leucócitos/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Regulação para Cima/efeitos dos fármacos
8.
Nat Immunol ; 20(7): 902-914, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209404

RESUMO

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.


Assuntos
Rim/imunologia , Nefrite Lúpica/imunologia , Biomarcadores , Biópsia , Análise por Conglomerados , Biologia Computacional/métodos , Células Epiteliais/metabolismo , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunofenotipagem , Interferons/metabolismo , Rim/metabolismo , Rim/patologia , Leucócitos/imunologia , Leucócitos/metabolismo , Nefrite Lúpica/genética , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Linfócitos/imunologia , Linfócitos/metabolismo , Anotação de Sequência Molecular , Células Mieloides/imunologia , Células Mieloides/metabolismo , Análise de Célula Única , Transcriptoma
9.
Nat Commun ; 10(1): 2491, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171785

RESUMO

Genetic factors underlying leukocyte telomere length (LTL) may provide insights into telomere homeostasis, with direct links to disease susceptibility. Genetic evaluation of 23,096 Singaporean Chinese samples identifies 10 genome-wide loci (P < 5 × 10-8). Several of these contain candidate genes (TINF2, PARP1, TERF1, ATM and POT1) with potential roles in telomere biology and DNA repair mechanisms. Meta-analyses with additional 37,505 European individuals reveals six more genome-wide loci, including associations at MPHOSPH6, NKX2-3 and TYMS. We demonstrate that longer LTL associates with protection against respiratory disease mortality [HR = 0.854(0.804-0.906), P = 1.88 × 10-7] in the Singaporean Chinese samples. We further show that the LTL reducing SNP rs7253490 associates with respiratory infections (P = 7.44 × 10-4) although this effect may not be strongly mediated through LTL. Our data expands on the genetic basis of LTL and may indicate on a potential role of LTL in immune competence.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Reparo do DNA/genética , Leucócitos/metabolismo , Homeostase do Telômero/genética , Telômero/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Respiratórias/genética , Singapura , Adulto Jovem
10.
Chem Biol Interact ; 308: 20-44, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31067438

RESUMO

Ischemic heart disease (IHD) is a major cause of cardiovascular morbidity and mortality worldwide, which is characterized by an imbalance between cardiac oxygen supply and demand predominantly due to obstruction of coronary arteries. Activation of the innate immune system and the consequent inflammatory response plays a role in the pathogenesis of IHD. Where an excessive inflammatory response may contribute to adverse cardiac remodeling and fibrosis, making inflammation an important therapeutic target for improving outcomes of IHD. While there are many discrepancies in the literature, evidence from both bench and clinical research demonstrate important effects of n-3 polyunsaturated fatty acids (n-3 PUFA), eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA), toward IHD. N-3 PUFAs, and their metabolites, have been demonstrated to modulate various components of the immune system, including regulation of chemokines and cytokines, leukocyte chemotaxis and inflammasome formation. In this article, we provide an overview of the role the innate immune system has in IHD and focus on the immunomodulatory effects of n-3 PUFAs and their biologically active metabolites.


Assuntos
Cardiotônicos/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Imunidade Inata , Isquemia Miocárdica/tratamento farmacológico , Alarminas/metabolismo , Cardiotônicos/farmacologia , Membrana Celular/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Ciclo-Oxigenase 1/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Humanos , Imunidade Inata/efeitos dos fármacos , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Isquemia Miocárdica/imunologia , Isquemia Miocárdica/patologia , Proteína-Lisina 6-Oxidase/metabolismo
11.
Int J Mol Sci ; 20(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075981

RESUMO

Decreased inflammatory status has been reported in subjects with mild unconjugated hyperbilirubinemia. However, mechanisms of the anti-inflammatory actions of bilirubin (BR) are not fully understood. The aim of this study is to assess the role of BR in systemic inflammation using hyperbilirubinemic Gunn rats as well as their normobilirubinemic littermates and further in primary hepatocytes. The rats were treated with lipopolysaccharide (LPS, 6 mg/kg intraperitoneally) for 12 h, their blood and liver were collected for analyses of inflammatory and hepatic injury markers. Primary hepatocytes were treated with BR and TNF-α. LPS-treated Gunn rats had a significantly decreased inflammatory response, as evidenced by the anti-inflammatory profile of white blood cell subsets, and lower hepatic and systemic expressions of IL-6, TNF-α, IL-1ß, and IL-10. Hepatic mRNA expression of LPS-binding protein was upregulated in Gunn rats before and after LPS treatment. In addition, liver injury markers were lower in Gunn rats as compared to in LPS-treated controls. The exposure of primary hepatocytes to TNF-α with BR led to a milder decrease in phosphorylation of the NF-κB p65 subunit compared to in cells without BR. In conclusion, hyperbilirubinemia in Gunn rats is associated with an attenuated systemic inflammatory response and decreased liver damage upon exposure to LPS.


Assuntos
Hiperbilirrubinemia/complicações , Inflamação/complicações , Animais , Apoptose/efeitos dos fármacos , Bilirrubina/farmacologia , Biomarcadores/sangue , Células Cultivadas , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Citoproteção/efeitos dos fármacos , Feminino , Hepatócitos/metabolismo , Hiperbilirrubinemia/sangue , Leucócitos/metabolismo , Lipopolissacarídeos , Fígado/metabolismo , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Gunn , Transdução de Sinais
12.
Fish Shellfish Immunol ; 91: 223-232, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31121289

RESUMO

With the fast growth of today's aquaculture industry, the demand for aquafeeds is expanding dramatically. Insects, which are part of the natural diet of salmonids, could represent a sustainable ingredient for aquaculture feed. The aim of the current study was to test how a partial or total replacement of dietary fishmeal with insect meal affect gene responses involved in inflammation, the eicosanoid pathway and stress response in Atlantic salmon (Salmo salar L.) in isolated head kidney leukocytes after exposure to bacterial or viral mimic. Insect meal (IM) was produced from black soldier fly (BSF, Hermetia illucens) larvae. Seawater Atlantic salmon were fed three different diets for 8 weeks; a control diet (IM0, protein from fishmeal and plant based ingredients (25:75) and lipid from fish oil and vegetable oil (33:66); and two insect-meal containing diets, IM66 and IM100, where 66 and 100% of the fishmeal protein was replaced with IM, respectively. Leukocytes were isolated from the head kidney of fish (n = 6) from each of the three dietary groups. Isolated leukocytes were seeded into culture wells and added either a bacterial mimic (lipopolysaccharide, LPS) or a viral mimic (polyinosinic acid: polycytidylic acid, poly I: C) to induce an inflammatory response. Controls (Ctl) without LPS and poly I: C were included. The transcription of interleukins IL-1ß, IL-8, IL-10 and TNF-α were elevated in LPS treated leukocytes isolated from salmon fed the three dietary groups (IM0, IM66 and IM100). The inflammatory-related gene expression in head kidney cells were, however, not affected by the pre-fed substitution of fish meal with IM in the diet of salmon. Gene transcriptions of PTGDS and PTGES were neither affected by LPS, poly I: C or the experimental diets fed prior to cell isolation, while salmon fed with IM showed a lower expression of LOX5. The gene expression of TLR22 and C/EBP-ß were down-regulated by the LPS treatment in the cells isolated from salmon fed insect-based diets (IM66 and IM100) compared to fish fed the IM0. Similarly, the leukocytes challenged with LPS and isolated from fish fed with IM66 and IM100 down-regulated the expression of Mn-SOD, GPx1, HSP27 and HSP70 compared to salmon fed IM0. In general, these results suggested that replacement of fishmeal with IM in the diets of Atlantic salmon had no effect on the transcription of pro-inflammatory genes in the head kidney cells. There was, however, an effect of dietary IM on the transcription of antioxidant and stress related genes in the leukocytes.


Assuntos
Dieta/veterinária , Dípteros/química , Rim Cefálico/imunologia , Leucócitos/imunologia , Salmo salar/genética , Salmo salar/imunologia , Ração Animal/análise , Animais , Peixes , Rim Cefálico/efeitos dos fármacos , Rim Cefálico/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Lipopolissacarídeos/farmacologia , Carne , Poli I-C/farmacologia , Distribuição Aleatória , Salmo salar/metabolismo
13.
Nat Immunol ; 20(7): 928-942, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31061532

RESUMO

To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)+HLA-DRAhi sublining fibroblasts, IL1B+ pro-inflammatory monocytes, ITGAX+TBX21+ autoimmune-associated B cells and PDCD1+ peripheral helper T (TPH) cells and follicular helper T (TFH) cells. We defined distinct subsets of CD8+ T cells characterized by GZMK+, GZMB+, and GNLY+ phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1+HLA-DRAhi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.


Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Perfilação da Expressão Gênica , Membrana Sinovial/metabolismo , Transcriptoma , Artrite Reumatoide/patologia , Autoimunidade/genética , Biomarcadores , Biologia Computacional/métodos , Estudos Transversais , Citocinas/metabolismo , Fibroblastos/metabolismo , Citometria de Fluxo , Expressão Gênica , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Leucócitos/imunologia , Leucócitos/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Transdução de Sinais , Análise de Célula Única/métodos , Membrana Sinovial/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Fluxo de Trabalho
14.
Molecules ; 24(9)2019 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-31083610

RESUMO

Optimal targeting of nanoparticles (NP) to dendritic cells (DCs) receptors to deliver cancer-specific antigens is key to the efficient induction of anti-tumour immune responses. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing tètanus toxoid and gp100 melanoma-associated antigen, toll-like receptor adjuvants were targeted to the DC-SIGN receptor in DCs by specific humanized antibodies or by ICAM3-Fc fusion proteins, which acts as the natural ligand. Despite higher binding and uptake efficacy of anti-DC-SIGN antibody-targeted NP vaccines than ICAM3-Fc ligand, no difference were observed in DC activation markers CD80, CD83, CD86 and CCR7 induced. DCs loaded with NP coated with ICAM3-Fc appeared more potent in activating T cells via cross-presentation than antibody-coated NP vaccines. This fact could be very crucial in the design of new cancer vaccines.


Assuntos
Vacinas Anticâncer/metabolismo , Células Dendríticas/metabolismo , Molécula 3 de Adesão Intercelular/metabolismo , Nanopartículas/química , Vacinas Anticâncer/química , Células Cultivadas , Humanos , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Leucócitos/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Receptores de IgG/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
15.
Methods Mol Biol ; 1968: 183-194, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30929215

RESUMO

Two-photon intravital imaging (2P-IVM) of the murine trachea is a powerful technique for real-time imaging of immune cell recruitment and trafficking during airborne pathogen infections. Neutrophils are an important component of the innate immune response that are able to rapidly infiltrate the airway mucosa in response to Streptococcus pneumoniae infection. Here we describe a protocol to visualize in vivo neutrophil extravasation and cell dynamics in the tracheal tissue of a S. pneumoniae-infected mouse using 2P-IVM. To perform this protocol, we infected and imaged the trachea of a lysozyme M green fluorescent protein (LysM-GFP) mouse, in which neutrophils express GFP. Additionally, we used a custom-designed platform, which allowed the intubation and fixation of the trachea after surgical exposition, and we injected intravenously a fluorescently labeled dextran solution to visualize the blood vessels.


Assuntos
Microscopia Intravital/métodos , Leucócitos/metabolismo , Infecções Pneumocócicas/diagnóstico , Infecções Pneumocócicas/microbiologia , Traqueia/diagnóstico por imagem , Traqueia/metabolismo , Animais , Proteínas de Fluorescência Verde/metabolismo , Camundongos , Neutrófilos/metabolismo , Streptococcus pneumoniae/patogenicidade
16.
Anal Cell Pathol (Amst) ; 2019: 8389765, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019876

RESUMO

Background: Chronic or intercurrent alterations of the immune system in patients with end-stage renal disease (CKD) and intermittent hemodialysis (CKD5D, HD) have been attributed to an acute rejection of renal allograft. Methods: Leukocyte subsets in flow cytometry, complement activation, and concentrations of TGFß, sCD30 (ELISA), and interleukins (CBA) of fifteen patients eligible for renal transplantation were analyzed before, during, and after a regular HD. Results: Before HD, the median proportion of CD8+ effector cells, CD8+ CCR5+ effector cells, and HLA-DR+ regulatory T cells as well as the median concentration of soluble CD30 increased and naive CD8+ T cells decreased. During HD, there was a significant decrease in CD4- CD8- T cells (p < 0.001) and an increase in CD25+ T cells (p = 0.026), sCD30 (p < 0.001), HLA-DR+ regulatory T cells (p = 0.005), and regulatory T cells (p = 0.003). TGFß and sCD30 increased significantly over time. The activity of the classical complement pathway started to slightly increase after the first hour of HD and lasted until fifteen minutes after finishing dialysis. The decrease in the functional activity of the alternative pathway was only transient and was followed by a significant increase within 15 minutes after finishing the treatment. Conclusion: HD might interact with the allograft outcome by influencing T cell subsets and activation of the complement system in a biphasic course.


Assuntos
Transplante de Rim/efeitos adversos , Diálise Renal/efeitos adversos , Adulto , Idoso , Linfócitos T CD8-Positivos/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucinas/metabolismo , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Linfócitos T/metabolismo , Adulto Jovem
17.
Lipids Health Dis ; 18(1): 80, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30935416

RESUMO

BACKGROUND: Evidence regarding the correlation between lipoproteins and telomere length in US adults is limited. We aimed to investigate whether lipoproteins was associated with telomere length using US National Health and Nutrition Examination Survey (NHANES) database. METHODS: A total of 6468 selected participants were identified in the NHANES Data Base (1999-2002). The independent and dependent variables were lipoproteins and telomere length, respectively. The covariates included demographic data, dietary data, physical examination data, and comorbidities. RESULTS: In fully-adjusted model, we found that 0.1 differences of telomere length were positively associated with HDL-C [0.19 (95% CI 0.07, 0.31)], while the associations between LDL-C [0.19 (95% CI -0.27, 0.65)], TG [- 1.00 (95% CI -2.09, 0.07) and telomere length were not detected. By nonlinearity test, only the relationship between HDL-C and telomere length was nonlinear. The inflection point we got was 1.25. On the left side of the inflection point (telomere length ≤ 1.25), a difference in 0.1 of telomere length was associated with 0.50 difference in HDL-C. CONCLUSION: After adjusting for demographic data, dietary data, physical examination data, and comorbidities, telomere length is not associated with LDL-C and TG, but is positively associated with HDL-C when telomere length is less than 1.25.


Assuntos
Hiperlipoproteinemia Tipo II/epidemiologia , Lipoproteínas/genética , Homeostase do Telômero/genética , Telômero/genética , Adulto , Idoso , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/patologia , Leucócitos/citologia , Leucócitos/metabolismo , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Fatores de Risco , Triglicerídeos/sangue
18.
Mater Sci Eng C Mater Biol Appl ; 100: 38-47, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30948074

RESUMO

In-vivo antibacterial property of Ti10Cu sintered alloy was investigated in comparison with pure titanium (cp-Ti) by implanting the alloys with S. aureus suspension in the muscles of rabbits. The general appearance, the white blood cell (WBC) number, the bacteria number were checked and the pathological examination were analyzed. It has been shown that serious inflammation at day 4 and fester at day 14 were observed after implantation in cp-Ti group while only mild infection was observed at day 4 in the case of Ti10Cu implants. Bacterial incubation results have also shown that lots of S. aureus were found in cp-Ti group at all intervals while only several bacteria at day 1 and day 4 and no bacteria after 7 days postimplantation can be found in Ti10Cu group. All these results demonstrate the strong in vivo antibacterial property of Ti10Cu alloy. The strong antibacterial property suggests that Ti10Cu alloy might have potential application in orthopedic surgery and dental implant to reduce the implant-related infection or inflammation.


Assuntos
Ligas/química , Cobre/química , Próteses e Implantes/microbiologia , Titânio/química , Ligas/farmacologia , Animais , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Teste de Materiais , Testes de Sensibilidade Microbiana , Músculos/patologia , Coelhos , Staphylococcus aureus/efeitos dos fármacos
19.
Oxid Med Cell Longev ; 2019: 6043245, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944694

RESUMO

Lipopolysaccharides (LPS) from Gram-negative bacteria prime human polymorphonuclear neutrophils (PMNs) via multicomponent receptor cluster including CD14 and MD-2·TLR4 for the enhanced release of reactive oxygen species (ROS) were triggered by bacterial derived peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). In this study, we investigated the impact of CD14 on LPS-induced priming of human PMNs for fMLP-triggered ROS generation (respiratory or oxidative) burst. Monoclonal antibodies against human CD14 (mAbs) as well as isotype-matched IgG2a did not influence significantly fMLP-triggered ROS production from LPS-unprimed PMNs. Anti-CD14 mAbs (clone UCHM-1) attenuated LPS-induced priming of PMNs as it had been mirrored by fMLP-triggered decrease of ROS production. Similar priming activity of S-LPS or Re-LPS from Escherichia coli for fMLP-triggered ROS release from PMNs was found. Obtained results suggest that glycosylphosphatidylinositol-anchored CD14 is the key player in LPS-induced PMN priming for fMLP-triggered ROS production. We believe that blockade of CD14 on the cell surface and clinical use of anti-CD14 mAbs or their Fab fragments may diminish the production of ROS and improve outcomes during cardiovascular diseases manifested by LPS-induced inflammation.


Assuntos
Escherichia coli/genética , Leucócitos/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/metabolismo , Escherichia coli/metabolismo , Humanos , Estresse Oxidativo , Espécies Reativas de Oxigênio
20.
Dev Comp Immunol ; 96: 1-8, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30822451

RESUMO

Lyn, a member of Src protein kinase family, plays a crucial role in immune reactions against pathogenic infection. In this study, Lyn from Nile tilapia (Oreochromis niloticus) (OnLyn) was identified and characterized at expression pattern against bacterial infection, and regulation function in BCR signaling. The open reading frame of OnLyn contained 1536 bp of nucleotide sequence encoded a protein of 511 amino acids. The OnLyn protein was highly conversed to other species Lyn, including SH3, SH2 and a catalytic Tyr kinase (TyrKc) domain. Transcriptional expression analysis revealed that OnLyn was detected in all examined tissues and was highly expressed in the head kidney. The up-regulation OnLyn expression was observed in the head kidney and spleen following challenge with Streptococcus agalactiae (S. agalactiae) in vivo, and was also displayed in head kidney leukocytes challenge with S. agalactiae and LPS in vitro. In addition, after induction with mouse anti-OnIgM mAb in vitro, the OnLyn expression and phosphorylation of OnLyn (Y507) were significantly up-regulated in the head kidney leukocytes. Moreover, after treatment with AZD0530 and mouse anti-OnIgM monoclonal antibody, the down-regulation of cytoplasmic free-Ca2+ concentration was detected in the head kidney leukocytes in vitro. Taken together, the findings of this study revealed that OnLyn might play potential roles in BCR signaling and get involved in host defense against bacterial infection in Nile tilapia.


Assuntos
Ciclídeos/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/imunologia , Streptococcus agalactiae/imunologia , Quinases da Família src/imunologia , Animais , Benzodioxóis/farmacologia , Cálcio/metabolismo , Ciclídeos/metabolismo , Ciclídeos/microbiologia , Resistência à Doença/imunologia , Proteínas de Peixes/metabolismo , Rim Cefálico/citologia , Rim Cefálico/imunologia , Rim Cefálico/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Leucócitos/imunologia , Leucócitos/metabolismo , Proteínas Proto-Oncogênicas c-bcr/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcr/metabolismo , Quinazolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima , Quinases da Família src/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA