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1.
Isr Med Assoc J ; 21(10): 658-661, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31599506

RESUMO

BACKGROUND: The incidence of Clostridium difficile-associated diarrhea (CDAD) is increasing and is associated with significant morbidity and mortality. Therefore, there is a need to find new tools to determine the severity of the disease. OBJECTIVES: To investigate the prognostic values of inflammatory markers such as mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLR), and C-reactive protein (CRP) in patients with CDAD. METHODS: The study comprised of 100 patients diagnosed with CDAD. The study included an additional control group of 69 patients with diarrhea who were negative for C. difficile toxin. The control group was age- and sex-matched and hospitalized at the same time period. NLR and MPV were obtained from complete blood count results. Serum CRP levels were measured by the latex particle enhanced immunoturbidimetric assay. Blood samples for all inflammatory markers were collected at time of diagnosis and prior to initiating the antibiotic therapy. Demographic, clinical, laboratory, and prognostic data were collected from medical records for a period of 90 days from the initial diagnosis of CDAD. RESULTS: The mean age of the CDAD group was 68.6 ± 21.5 years compared to 65.6 ± 24.5 in the control group (P = 0.29). Our findings show that patients with CDAD had significantly higher NLR, MPV and serum CRP levels compared to the control group (P < 0.001)). Moreover, significantly higher levels were observed when CDAD was fatal (P < 0.001). CONCLUSIONS: Elevated NLR, MPV, and serum CRP levels may serve as biomarkers for prediction of recurrence and mortality in patients with CDAD.


Assuntos
Infecções por Clostridium/sangue , Infecções por Clostridium/complicações , Clostridium difficile/patogenicidade , Diarreia/microbiologia , Inflamação/sangue , Inflamação/microbiologia , Idoso , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Infecções por Clostridium/diagnóstico , Diarreia/sangue , Feminino , Humanos , Linfócitos/metabolismo , Masculino , Volume Plaquetário Médio/estatística & dados numéricos , Neutrófilos/metabolismo , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
2.
Medicine (Baltimore) ; 98(43): e17537, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651856

RESUMO

Neutrophil-to-lymphocyte ratio (NLR) serves as a strong prognostic indicator for patients suffering from various diseases. Neutrophil activation promotes the recruitment of a number of different cell types that are involved in acute and chronic inflammation and are associated with cancer treatment outcome. Measurement of NLR, an established inflammation marker, is cost-effective, and it is likely that NLR can be used to predict the development of metabolic syndrome (MS) at an early stage. MS scores range from 1 to 5, and an elevated MS score indicates a greater risk for MS. Monitoring NLR can prevent the risk of MS.A total of 34,013 subjects were enrolled in this study. The subjects (score 0-5) within the 6 groups were classified according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, and all anthropometrics, laboratory biomarkers, and hematological measurements were recorded. For the 6 groups, statistical analysis and receiver operating characteristic (ROC) curves were used to identify the development of MS.Analysis of the ROC curve indicated that NLR served as a good predictor for MS. An MS score of 1 to 2 yielded an acceptable discrimination rate, and these rates were even higher for MS scores of 3 to 5 (P < .001), where the prevalence of MS was 30.8%.NLR can be used as a prognostic marker for several diseases, including those associated with MS.


Assuntos
Linfócitos/metabolismo , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Neutrófilos/metabolismo , Medição de Risco/métodos , Adulto , Biomarcadores/sangue , Feminino , Humanos , Contagem de Linfócitos , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco
3.
Medicine (Baltimore) ; 98(32): e16801, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393410

RESUMO

BACKGROUND: Contrast-induced nephropathy (CIN) is acute renal failure observed after administration of iodinated contrast media during angiographic or other medical procedures. In recent years, many studies have focused on biomarkers that recognize CIN and/or predict its development in advance. One of the many biomarkers studied is the platelet-to-lymphocyte ratio (PLR). We performed a systematic review and meta-analysis to evaluate the correlation between PLR level and CIN. METHODS: Relevant studies were searched in PUBMED, EMBASE, and Web of Science until September 15, 2018. Case-control studies reporting admission PLR levels in CIN and non-CIN group in patients with acute coronary syndrome (ACS) were included. The pooled weighted mean difference (WMD) and 95% confidence intervals (95%CI) were calculated to assess the association between PLR level and CIN using a random-effect model. RESULTS: Six relevant studies involving a total of 10452 ACS patients (9720 non-CIN controls and 732 CIN patients) met our inclusion criteria. A meta-analysis of 6 case-control studies showed that PLR levels were significantly higher in CIN group than those in non-CIN group (WMD = 33.343, 95%CI = 18.863 to 47.823, P < .001, I = 88.0%). CONCLUSION: For patients with ACS after contrast administration, our meta-analysis shows that on-admission PLR levels in CIN group are significantly higher than those of non-CIN group. However, large and matched cohort studies are needed to validate these findings and assess whether there is a real connection or just an association.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Lesão Renal Aguda/induzido quimicamente , Plaquetas/metabolismo , Meios de Contraste/efeitos adversos , Linfócitos/metabolismo , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/cirurgia , Angiografia Coronária/efeitos adversos , Angiografia Coronária/métodos , Humanos , Contagem de Linfócitos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos
4.
Medicine (Baltimore) ; 98(34): e16793, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441851

RESUMO

Osteoporosis is a chronic, progressive disease in which early diagnosis is very important. The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have been reported as new predictors in inflammatory and immune diseases including osteoporosis. No studies have reported the relationship between monocyte-to-lymphocyte ratio (MLR) and osteoporosis patients.To investigated the ability of MLR to predict osteoporosis.Three hundred sixteen osteoporosis patients and 111 healthy control subjects were enrolled. Patients' laboratory and clinical characteristics were recorded. MLR, NLR, and PLR levels were calculated. The differences were compared and the diagnostic values of MLR were analyzed.There were 76 male and 105 female patients included, with a mean age of 56.57 ±â€Š9.95 years. The levels of MLR, NLR, and PLR in osteoporosis patients were all higher than those in healthy control subjects. The area under the curve of MLR was higher than those of NLR and PLR. Multivariate linear regression analysis showed that T-score was affected by age and MLR. MLR was positively correlated with C-reactive protein, erythrocyte sedimentation rate, red blood cell distribution width, age, sex, and inversely with hemoglobin. MLR and PLR levels were significantly higher in osteoporosis patients than in osteopenia patients (P < .05).The present study shows that MLR had a higher diagnostic value for osteoporosis. MLR may be a reliable, inexpensive, and novel potential predictor of osteoporosis.


Assuntos
Linfócitos/metabolismo , Monócitos/metabolismo , Osteoporose/sangue , Adulto , Fatores Etários , Idoso , Plaquetas/metabolismo , Sedimentação Sanguínea , Proteína C-Reativa/biossíntese , Estudos Transversais , Feminino , Hemoglobinas/análise , Humanos , Mediadores da Inflamação/metabolismo , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
5.
Anticancer Res ; 39(7): 3745-3755, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262901

RESUMO

BACKGROUND/AIM: The study is directed to the effect of resveratrol on the redox-status and viability of leukemic and normal lymphocytes, as well as its ability to sensitize leukemic lymphocytes to anticancer drugs. MATERIALS AND METHODS: Cytotoxicity was analyzed by trypan blue staining, apoptosis - by Annexin V test, and oxidative stress - by the intracellular levels of reactive oxygen species (ROS) and protein-carbonyl products. RESULTS: Incubation of resveratrol in combination with the majority of anticancer drugs resulted in higher toxicity than resveratrol or drug alone. In the case of leukemic lymphocytes treated with barasertib and everolimus in the presence of resveratrol, synergistic cytotoxicity was accompanied by strong induction of apoptosis, increased levels of hydroperoxides and insignificant changes in protein-carbonyl products. None of these parameters changed in normal lymphocytes. CONCLUSION: Resveratrol is a promising supplementary compound for anticancer therapy, that may allow reduction of the therapeutic doses of barasertib and everolimus, minimizing their side-effects.


Assuntos
Antineoplásicos/farmacologia , Leucemia/metabolismo , Linfócitos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Resveratrol/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Leucemia/tratamento farmacológico , Linfócitos/metabolismo , Oxirredução
6.
Nat Commun ; 10(1): 2712, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221971

RESUMO

Clostridium difficile (C. difficile) incidence has tripled over the past 15 years and is attributed to the emergence of hypervirulent strains. While it is clear that C. difficile toxins cause damaging colonic inflammation, the immune mechanisms protecting from tissue damage require further investigation. Through a transcriptome analysis, we identify IL-33 as an immune target upregulated in response to hypervirulent C. difficile. We demonstrate that IL-33 prevents C. difficile-associated mortality and epithelial disruption independently of bacterial burden or toxin expression. IL-33 drives colonic group 2 innate lymphoid cell (ILC2) activation during infection and IL-33 activated ILC2s are sufficient to prevent disease. Furthermore, intestinal IL-33 expression is regulated by the microbiota as fecal microbiota transplantation (FMT) rescues antibiotic-associated depletion of IL-33. Lastly, dysregulated IL-33 signaling via the decoy receptor, sST2, predicts C. difficile-associated mortality in human patients. Thus, IL-33 signaling to ILC2s is an important mechanism of defense from C. difficile colitis.


Assuntos
Clostridium difficile/imunologia , Enterocolite Pseudomembranosa/imunologia , Imunidade Inata , Interleucina-33/metabolismo , Linfócitos/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antibacterianos/efeitos adversos , Toxinas Bacterianas/imunologia , Toxinas Bacterianas/metabolismo , Clostridium difficile/patogenicidade , Colo/citologia , Colo/imunologia , Colo/microbiologia , Colo/patologia , Modelos Animais de Doenças , Enterocolite Pseudomembranosa/microbiologia , Enterocolite Pseudomembranosa/mortalidade , Enterocolite Pseudomembranosa/terapia , Transplante de Microbiota Fecal , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Perfilação da Expressão Gênica , Humanos , Interleucina-33/imunologia , Linfócitos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologia , Virulência/imunologia , Adulto Jovem
7.
Environ Pollut ; 252(Pt A): 607-615, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31185349

RESUMO

Coke oven emissions (COEs) are common particle pollutants in occupational environment and the major constituents of COEs are polycyclic aromatic hydrocarbons (PAHs). Previously, we identified aberrant methylation of the fms related tyrosine kinase 1 (FLT1) gene over the course of benzo(a)pyrene (BaP)-induced cell transformation via genome-wide methylation array. To quantify FLT1 methylation, we established a bisulfite pyrosequencing assay and examined the FLT1 hypermethylation in several human cancers. The results revealed that 70.0% (21/30 pairs) of lung cancers harbored hypermethylated FLT1 and concomitant suppression of gene expression compared to the adjacent tissues. This implies that FLT1 hypermethylation might play a role in malignant cell transformation. In addition, FLT1 hypermethylation and gene suppression appeared in primary human lymphocytes in a dose-response manner following COEs treatment. To explore whether FLT1 methylation is correlated with COEs exposure and DNA damage, we recruited 144 male subjects who had been exposed to high levels of COEs and 84 male control subjects. Notably, the FLT1 methylation in peripheral blood lymphocytes (PBLCs) of the COEs-exposed group (19.8 ±â€¯3.2%) was enhanced by 17.9% compared to that of the control group (16.8 ±â€¯2.8%) (P < 0.001). The FLT1 methylation status was positively correlated with urinary 1-hydroxypyrene (1-OHP) levels, an internal exposure marker of PAHs (ß = 0.029, 95% CI = 0.010-0.048, P = 0.003) and positively correlated with DNA damage (ßOTM = 0.024, 95% CI = 0.007-0.040, P = 0.005; ßTail DNA = 0.035, 95% CI = 0.0017-0.054, P < 0.001) indicated by comet assay. Taken together, these findings indicate that FLT1 might be a tumor suppressor, and its hypermethylation might contribute to PAHs-induced carcinogenicity.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Adulto , Poluentes Ocupacionais do Ar/análise , Benzo(a)pireno/metabolismo , Biomarcadores/metabolismo , Transformação Celular Neoplásica/metabolismo , Coque , Ensaio Cometa , Dano ao DNA , Metilação de DNA , Humanos , Linfócitos/metabolismo , Masculino , Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos/análise , Pirenos/metabolismo , Sulfitos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular
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.
Nord J Psychiatry ; 73(4-5): 288-292, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31164025

RESUMO

Background: Neuroleptic malignant syndrome (NMS) is a life-threatening side effect of antipsychotic medication. In this study, we aimed to investigate the hypothesis of inflammation via neutrophil-lymphocyte ratio (NLR) in the etiology of NMS. Methods: In this retrospective case-control study, data were collected using digital database of Bakirköy Mental Health Research and Training State Hospital by screening NMS diagnosis according to 'International Classification of Diseases (ICD-10) code: G21.0' between the years of 2007 and 2017. We included 32 hospitalizations with the diagnosis of NMS and 31 other acute psychiatric hospitalizations without NMS of same patients. NLR was calculated as proportion of absolute neutrophil count to absolute lymphocyte count. Significance level was accepted as p < .05. Results: The mean NLR value of NMS group was 9.55 ± 5.13 and control group was 2.06 ± 0.71 (p < .001). According to ROC analysis in our study group, we found a mean NLR cutoff value ≥4 and lymphocyte percent cutoff of ≤18.4% have the probability of correctly identifying patients with NMS with the 100% sensitivity and 100% specificity. Conclusions: In this retrospective study, we considered that higher NLR value in NMS episode might be a resemblance of systemic inflammatory state. In addition, our results suggest that both NLR and lymphocyte percentage may be alternative minor criteria which are more sensitive and specific than leukocyte levels and CPK.


Assuntos
Antipsicóticos/efeitos adversos , Linfócitos/metabolismo , Síndrome Maligna Neuroléptica/sangue , Síndrome Maligna Neuroléptica/diagnóstico , Neutrófilos/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Contagem de Leucócitos/métodos , Contagem de Linfócitos/métodos , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Estudos Retrospectivos
10.
Cell Mol Life Sci ; 76(20): 3917-3937, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31250035

RESUMO

The gastrointestinal tract is the site of nutrient digestion and absorption and is also colonized by diverse, highly mutualistic microbes. The intestinal microbiota has diverse effects on the development and function of the gut-specific immune system, and provides some protection from infectious pathogens. However, interactions between intestinal immunity and microorganisms are very complex, and recent studies have revealed that this intimate crosstalk may depend on the production and sensing abilities of multiple bioactive small molecule metabolites originating from direct produced by the gut microbiota or by the metabolism of dietary components. Here, we review the interplay between the host immune system and the microbiota, how commensal bacteria regulate the production of metabolites, and how these microbiota-derived products influence the function of several major innate and adaptive immune cells involved in modulating host immune homeostasis.


Assuntos
Imunidade Adaptativa , Disbiose/metabolismo , Microbioma Gastrointestinal/imunologia , Imunidade Inata , Mucosa Intestinal/metabolismo , Metaboloma/imunologia , Aminoácidos/imunologia , Aminoácidos/metabolismo , Animais , Ácidos e Sais Biliares/imunologia , Ácidos e Sais Biliares/metabolismo , Disbiose/imunologia , Disbiose/microbiologia , Disbiose/terapia , Ácidos Graxos/imunologia , Ácidos Graxos/metabolismo , Transplante de Microbiota Fecal , Vida Livre de Germes/imunologia , Homeostase/imunologia , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos/microbiologia , Células Mieloides/imunologia , Células Mieloides/metabolismo , Células Mieloides/microbiologia , Simbiose/imunologia
11.
Int J Nanomedicine ; 14: 3403-3411, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190799

RESUMO

Aim: To quantitatively and sensitively investigate the biodistribution of immune cells after systemic administration. Methods: Immune cells were loaded with plasmonic gold nanostars (GNS) tracking probes. Inductively coupled plasma mass spectrometry (ICP-MS) was used for quantitative gold mass measurement and two-photon photoluminescence (TPL) was used for high-resolution sensitive optical imaging. Results: GNS nanoparticles were loaded successfully into immune cells without negative effect on cellular vitality. Liver and spleen were identified to be the major organs for macrophage cells uptake after systematic administration. A small amount of macrophage cells were detected in the tumor site in our murine lymphoma animal model. Conclusion: GNS has great potential as a biocompatible marker for quantitative tracking and high-resolution imaging of immune cells at the cellular level.


Assuntos
Ouro/química , Linfócitos/metabolismo , Nanopartículas Metálicas/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Macrófagos/metabolismo , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/ultraestrutura , Camundongos Endogâmicos C57BL , Distribuição Tecidual
12.
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
13.
J Photochem Photobiol B ; 196: 111496, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129507

RESUMO

Surgical resection is one of the most common radical treatments for cancers. However, tumors may be compressed or the local intravascular pressure may be increased during surgical manipulation, causing the shedding and entry of tumor cells into the blood circulation and hence distant recurrence and metastasis of tumors. We have preliminarily established a method of riboflavin photosensitization treatment (RPT) for inactivation of circulating tumor cells. This technology promises to solve the problems of shedding and entry of solid tumor cells into blood circulation before surgical manipulation, and almost unavoidable hematogenous dissemination of tumor cells during surgical resection. In the present study, apoptosis detection and tumorigenicity experiment in immunodeficient mice were conducted to evaluate the effect of RPT for inactivation of circulating tumor cells respectively. Next, functional evaluation was carried out for the immune cells through detecting apoptosis rate and cytokine secretion of lymphocyte. Finally, thromboelastography (TEG) and free hemoglobin were detected to assess peripheral blood coagulation and red blood cell damage. The results showed that RPT (50 µmol/L riboflavin, 10.8 J/cm2 UV) could effectively make tumor cell lose the ability of proliferation in the peripheral blood. In the meantime, the damage caused to peripheral blood coagulation, immune cell function and red blood cells was generally acceptable. The results of the study showed that RPT had huge potential in addressing the problems of shedding and entry of solid tumor cells into blood circulation before surgical manipulation, and almost unavoidable hematogenous dissemination of tumor cells during surgical resection. This therapy is expected to be an auxiliary and supportive method to reduce the risk of hematogenous metastasis and recurrence of cancers, and to increase the surgical success rate of malignant solid tumors.


Assuntos
Células Neoplásicas Circulantes/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Riboflavina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Coagulação Sanguínea/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Células HCT116 , Hemólise/efeitos dos fármacos , Humanos , Luz , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias/tratamento farmacológico , Células Neoplásicas Circulantes/metabolismo , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico
14.
Environ Sci Pollut Res Int ; 26(20): 20654-20668, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104239

RESUMO

Copper (Cu) is widely used in various industries, and human exposure to this metal results in severe multi-organ toxicity, which is thought to be due to the generation of free radicals by Fenton-like reaction. The generation of reactive oxygen as well as nitrogen species and free radicals results in induction of oxidative stress in the cell. We have studied the effect of different concentrations of Cu(II) on human erythrocytes and lymphocytes. Incubation of erythrocytes with copper chloride, a Cu(II) compound, enhanced the production of reactive oxygen and nitrogen species, decreased glutathione and total sulphydryl content and increased protein oxidation and lipid peroxidation. All changes were in a Cu(II) concentration-dependent manner. This strongly suggests that Cu(II) causes oxidative damage in erythrocytes. The activities of major antioxidant enzymes were altered, and antioxidant power was lowered. Cu(II) treatment also resulted in membrane damage in erythrocytes as seen by electron microscopy and lowered activities of plasma membrane-bound enzymes. Incubation of human lymphocytes with Cu(II) resulted in DNA damage when studied by the sensitive comet assay. These results show that Cu(II) exerts cytotoxic and genotoxic effects on human blood cells probably by enhancing the generation of reactive oxygen and nitrogen species.


Assuntos
Antioxidantes/metabolismo , Cobre/toxicidade , Dano ao DNA/efeitos dos fármacos , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Membrana Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/patologia , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Linfócitos/patologia , Estresse Oxidativo/efeitos dos fármacos
15.
Mediators Inflamm ; 2019: 6513847, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049026

RESUMO

Introduction: Atherosclerosis is a low-grade inflammatory disease. Among markers of inflammation, importance has been given to the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR). The objective of this study was to examine the association between these hematological indices of inflammation and coronary atherosclerotic calcification in clinically asymptomatic patients. Methods: This study had clinical and laboratorial data collected from consecutive asymptomatic patients that underwent computed tomography coronary artery calcium (CAC) scoring. Risk factors, NLR, and PLR were evaluated at different categories of CAC scoring. Statistical tests included chi-square, linear regression, and logistic regression. Patients (N = 247; age 60.4 ± 8.0 years and 60.7% men) were allocated into four categories according to the CAC score. Results: Respective age, sex (male), NLR, and PLR distribution within groups were as follows: CAC = 0 (n = 98; 52.5 ± 13.6 years, 55%, 2.0 ± 1.0, and 121.5 ± 41.5), CAC 1-100 (N = 64; 61.3 ± 11.0 years, 60%, 2.2 ± 1.2, and 125.6 ± 45.6), CAC 101-400 (N = 37; 64.2 ± 11.6 years, 67%, 2.6 ± 1.3, and 125.4 ± 55.9), and CAC > 400 (N = 48; 69.3 ± 11.1 years, 66%, 3.3 ± 2.0, and 430.1 ± 1787.4). The association between risk factors and CAC score was assessed. Hypertension status and smoking status were similar within groups, while the presence of diabetes (P = 0.02) and older age (P ≤ 0.001) was more prevalent in the CAC > 400 group. LDL cholesterol was greater in the higher CAC score groups (P = 0.002). Multivariate logistic regression of the quartile analysis showed that age and NLR were independently associated with CAC > 100 (OR (CI), P value): 2.06 (1.55-2.73, P = 0.00001) and 1.82 (1.33-2.49, P = 0.0002), respectively. Conclusion: Within asymptomatic patients, NLR provides additional risk stratification, as an independent association between NLR extent and CAD extent was identified. Moreover, PLR was not an inflammation marker for CAD severity.


Assuntos
Linfócitos/metabolismo , Neutrófilos/metabolismo , Idoso , Plaquetas/metabolismo , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos
16.
Environ Pollut ; 252(Pt A): 39-50, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31146237

RESUMO

Exposure to ultrafine particulate matter (PM0.1) is positively associated with the etiology of different acute and chronic disorders; however, the in-depth biological imprints that link these submicron particles with the disturbances in the epigenomic machinery are not well defined. Earlier, we showed that exposure to these particles causes significant disturbances in the mitochondrial machinery and triggers PI-3-kinase mediated DNA damage responses. In the present study, we aimed to further understand the epigenomic insights of the ultrafine PM exposure. The higher levels of intracellular reactive oxygen species and depleted Nrf-2 in ultrafine PM exposed cells reconfirmed its potential to induce oxidative stress. Importantly, the observed increase in the levels of NF-κß and associated cytokines among exposed cells suggested the activation of NF-κß mediated inflammatory loop which potentially serves as a platform for initiating epigenetic insinuations. This fact was strongly supported by the altered miRNA expression profile of the ultrafine PM exposed cells. These NF-κß induced miRNA alterations were also found to be associated with other epigenetic targets as the exposed cells showed higher expression levels of DNA methyltransferases which positively corresponded with the global changes in DNA methylation levels. Upon further analysis, significant alterations in histone code were also reported in ultrafine PM exposed cells. Conclusively our results suggested that NF-κß acts as an inflammatory switch that possesses the potential to induce genome-wide epigenetic modification upon ultrafine PM exposure.


Assuntos
Metilação de DNA/efeitos dos fármacos , Epigênese Genética/genética , Linfócitos/metabolismo , NF-kappa B/metabolismo , Material Particulado/toxicidade , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Dano ao DNA/efeitos dos fármacos , Metilases de Modificação do DNA/biossíntese , Humanos , MicroRNAs/biossíntese , MicroRNAs/genética , Mitocôndrias/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia , Tamanho da Partícula , Material Particulado/análise , Fosfatidilinositol 3-Quinase/metabolismo , Espécies Reativas de Oxigênio/metabolismo
17.
Am J Vet Res ; 80(6): 572-577, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31140843

RESUMO

OBJECTIVE: To investigate luteinizing hormone (LH) receptor expression in canine nonneoplastic and neoplastic lymph nodes, circulating nonneoplastic lymphocytes, and T-cell lymphoma (TCL) cell lines. SAMPLE: Formalin-fixed, paraffin-embedded lymph nodes (5 neoplastic and 3 nonneoplastic) from 6 dogs, circulating lymphocytes from venous blood specimens obtained from 12 healthy dogs, and 3 TCL cell lines derived from 3 dogs with primary lymphoma. PROCEDURES: Lymph node specimens were immunohistochemically stained for determination of LH receptor expression. Circulating nonneoplastic lymphocytes and TCL cell lines were evaluated for LH receptor expression by use of flow cytometry; circulating lymphocytes were also immunophenotyped. The mean percentage of cells positive for LH receptors was determined for each type of specimen. For the healthy dogs, percentages of circulating B and T lymphocytes that expressed LH receptors were assessed on the basis of sex and reproductive status. RESULTS: The mean percentage of LH receptor-positive cells in canine neoplastic and nonneoplastic lymph nodes was 12.4% and 4.1%, respectively. For the healthy dogs, the mean percentage of circulating LH receptor-positive T lymphocytes was significantly higher in gonadectomized dogs (16.6%) than in sexually intact dogs (10.5%); the percentages of circulating LH receptor-positive B lymphocytes did not significantly differ by reproductive status. Among the 3 canine TCL cell lines, LH receptor expression ranged from 10% to 45%. CONCLUSIONS AND CLINICAL RELEVANCE: In this study, LH receptor expression by canine neoplastic and nonneoplastic lymphocytes was detected. Research into the effects of downregulation of LH receptor activation in dogs with lymphoma is warranted.


Assuntos
Doenças do Cão/metabolismo , Linfócitos/metabolismo , Linfoma/veterinária , Receptores do LH/biossíntese , Linfócitos T/metabolismo , Animais , Linhagem Celular Tumoral , Doenças do Cão/imunologia , Doenças do Cão/patologia , Cães , Feminino , Citometria de Fluxo/veterinária , Linfonodos/metabolismo , Linfoma/imunologia , Linfoma/metabolismo , Masculino
18.
Medicine (Baltimore) ; 98(18): e15369, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045780

RESUMO

BACKGROUND: To evaluate the impact of neutrophil-to-lymphocyte ratios (NLR) as a prognostic factor in predicting treatment outcomes after radiotherapy (RT) for solid tumors. METHODS: PubMed and Embase databases were used to search for articles published by February 2019 based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Hazard ratios (HR) with 95% confidence intervals (CI) were used to evaluate the association between NLR levels and treatment outcomes after RT. The primary endpoint was overall survival (OS) rates. Secondary endpoints included progression-free survival, disease-free survival, and disease-specific survival rates. RESULTS: Thirty-eight datasets with a total of 7065 patients were included in the meta-analysis. Patients with high pretreatment NLR demonstrated significantly worse OS with a pooled HR of 1.90 (95% CI 1.66-2.17, P < .001). In patients receiving RT alone, the pooled HR for OS was 1.71 (95% CI 1.44-2.04, P < .001) with no between-study heterogeneity (I = 0%, P = .46). CONCLUSION: Elevated pretreatment NLR is associated with poorer survival in cancer patients undergoing RT. Elevated pretreatment NLR prior to RT initiation may be a useful biomarker to predict treatment outcomes and select a subgroup of patients in need of a more aggressive treatment approach.


Assuntos
Linfócitos/metabolismo , Neoplasias/sangue , Neoplasias/radioterapia , Neutrófilos/metabolismo , Biomarcadores Tumorais , Quimioterapia Adjuvante , Humanos , Contagem de Linfócitos , Neoplasias/mortalidade , Neoplasias/terapia , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida
19.
Int J Mol Sci ; 20(10)2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31096567

RESUMO

The tumor microenvironment plays a pillar role in the progression and the distance dissemination of cancer cells in the main malignancies affecting women-epithelial ovarian cancer, endometrial cancer and cervical cancer. Their milieu acquires specific properties thanks to intense crosstalk between stromal and cancer cells, leading to a vicious circle. Fibroblasts, pericytes, lymphocytes and tumor associated-macrophages orchestrate most of the biological pathways. In epithelial ovarian cancer, high rates of activated pericytes determine a poorer prognosis, defining a common signature promoting ovarian cancer proliferation, local invasion and distant spread. Mesenchymal cells also release chemokines and cytokines under hormonal influence, such as estrogens that drive most of the endometrial cancers. Interestingly, the architecture of the cervical cancer milieu is shaped by the synergy of high-risk Human Papilloma Virus oncoproteins and the activity of stromal estrogen receptor α. Lymphocytes represent a shield against cancer cells but some cell subpopulation could lead to immunosuppression, tumor growth and dissemination. Cytotoxic tumor infiltrating lymphocytes can be eluded by over-adapted cancer cells in a scenario of immune-tolerance driven by T-regulatory cells. Therefore, the tumor microenvironment has a high translational potential offering many targets for biological and immunological therapies.


Assuntos
Neoplasias do Endométrio/metabolismo , Neoplasias Ovarianas/metabolismo , Células Estromais/metabolismo , Microambiente Tumoral/fisiologia , Neoplasias do Colo do Útero/metabolismo , Actinas , Quimiocinas/metabolismo , Citocinas/metabolismo , Neoplasias do Endométrio/imunologia , Receptor alfa de Estrogênio/metabolismo , Estrogênios/metabolismo , Feminino , Fibroblastos/metabolismo , Humanos , Tolerância Imunológica , Linfócitos/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Macrófagos/metabolismo , Mesoderma/metabolismo , Proteínas Oncogênicas/metabolismo , Neoplasias Ovarianas/imunologia , Papillomaviridae , Pericitos/metabolismo , Receptor beta de Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais , Células Estromais/imunologia , Microambiente Tumoral/imunologia , Neoplasias do Colo do Útero/imunologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-31124426

RESUMO

OBJECTIVES: Gliclazide (GL) is widely used to reduce hyperglycemia in diabetic patients. The aim of this study was to investigate the protective effect of GL against chromosome damage induced by ionizing radiation in human blood lymphocytes. METHODS: In this experimental study, peripheral blood samples were collected from human volunteers and treated with GL at various concentrations (5, 25, 50 or 100 µM) for three hours. Then samples were irradiated to X-ray (1.5 Gy). Blood samples were cultured with mitogenic stimulation. The frequencies of micronuclei in cytokinesis-blocked binucleated lymphocytes were determined in the different samples. The antioxidant activities of GL were assayed by two different methods as 1,1- diphenyl-2-picryl hydrazyl radical (DPPH) free radical scavenging and reducing antioxidant power assays. RESULTS: GL significantly reduced the percentage of micronuclei in lymphocytes which were irradiated. The maximum radioprotection in the reduction of percentage of micronuclei in lymphocytes was observed at 100 µM of GL with 52% efficacy. GL exhibited excellent free radical scavenging activity and reducing power at concentration dependent activities. The IC50 values of GL were lower than ascorbic acid. Higher potencies were observed in the antioxidant activities for GL than ascorbic acid in both methods. CONCLUSION: This data exhibits that GL is a powerful radioprotective agent that could protect healthy cells against the chromosome damage induced by ionizing radiation through antioxidant activity. The radioprotective effect is new indication of GL for patient's protection against side effect induced by ionizing radiation.


Assuntos
Gliclazida/farmacologia , Linfócitos/efeitos dos fármacos , Linfócitos/efeitos da radiação , Protetores contra Radiação/farmacologia , Raios X/efeitos adversos , Antioxidantes/farmacologia , Células Cultivadas , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Humanos , Hipoglicemiantes/farmacologia , Linfócitos/metabolismo
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