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1.
Anticancer Res ; 39(9): 5009-5018, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519608

RESUMO

BACKGROUND/AIM: Interleukin (IL)-18, which belongs to the IL-1 superfamily of cytokines, is a known interferon-gamma (IFN-γ)-inducing factor. Since IFN-γ plays an essential role in anticancer immunity mediated through cytotoxic T cells, IL-18 may also contribute to the function of immunosurveillance. The aim of the study was to examine the association of IL-18 with the outcomes of patients with breast cancer. PATIENTS AND METHODS: Serum IL-18 levels were determined at baseline in 270 patients operated for breast cancer, and the relapse-free survival (RFS) was compared between IL-18-high and -low groups. The relationships between IL-18 and tumor-infiltrating lymphocytes (TILs) or the neutrophil-to-lymphocyte ratio (NLR) were also investigated. RESULTS: The RFS of patients was significantly better in the IL-18-low group than in the IL-18-high group (p=0.032). According to the multivariate analysis, IL-18 was a significant and independent predictive factor for RFS (hazard ratio(HR)=0.336; 95% confidence interval(CI)=0.147-0.727; p=0.0053). No association was observed between the IL-18 levels and TILs or NLRs. CONCLUSION: IL-18 levels may be useful for predicting the prognosis of patients who have received surgical treatment for breast cancer.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Interleucina-18/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Citocinas/sangue , Citocinas/metabolismo , Feminino , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neutrófilos/imunologia , Neutrófilos/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Valores de Referência , Estudos Retrospectivos , Carga Tumoral
2.
Medicine (Baltimore) ; 98(32): e16462, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393350

RESUMO

The outcome of patients with acute type B aortic dissection (BAAD) is largely dictated by whether or not the case is "complicated." The purpose of this study was to investigate the risk factors leading to in-hospital death among patients with BAAD and then to develop a predictive model to estimate individual risk of in-hospital death.A total of 188 patients with BAAD were enrolled. Risk factors for in-hospital death were investigated with univariate and multivariable logistic regression analysis. Significant risk factors were used to develop a predictive model.The in-hospital mortality rate was 9% (17 of 188 patients). Univariate analysis revealed 7 risk factors to be statistically significant predictors of in-hospital death (P < .1). In multivariable analysis, the following variables at admission were independently associated with increased in-hospital mortality: hypotension (odds ratio [OR], 4.85; 95% confidence interval [CI], 1.12-18.90; P = .04), ischemic complications (OR, 8.24; 95% CI, 1.25-33.85; P < .001), renal dysfunction (OR, 12.32; 95% CI, 10.63-76.66; P < .001), and neutrophil percentage ≥80% (OR, 5.76; 95% CI, 2.58-12.56; P = .03). Based on these multivariable results, a reliable and simple prediction model was developed, a total score of 4 offered the best point value.Independent risk factors associated with in-hospital death can be predicted in BAAD patients. The prediction model could be used to identify the prognosis for BAAD patients and assist physicians in their choice of management.


Assuntos
Aneurisma Dissecante/mortalidade , Aneurisma da Aorta Torácica/mortalidade , Mortalidade Hospitalar , Adulto , Idoso , Aneurisma Dissecante/classificação , Aneurisma Dissecante/terapia , Aneurisma da Aorta Torácica/classificação , Aneurisma da Aorta Torácica/terapia , Comorbidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Razão de Chances , Fatores de Risco
3.
Medicine (Baltimore) ; 98(35): e17059, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464966

RESUMO

BACKGROUND: Delta neutrophil index (DNI) is the ratio of the number of immature granulocytes and the total neutrophil count in peripheral circulation. DNI precedes changes in white blood cell or neutrophil counts due to the course of granular leukocyte differentiation in infectious and inflammatory conditions, beginning with immature granulocyte formation. The role of DNI as a biomarker of various infectious or inflammatory conditions has been reported. However, no studies explored the potential role of DNI as an initial biomarker for predicting disease severity, surgical outcomes, and mortality rates of gastrointestinal diseases with pooled diagnostic test accuracy. This study aims to provide evidence that DNI is a predictor of disease severity, surgical outcomes, and mortality rates in patients with gastrointestinal diseases in emergency medical departments. METHODS: MEDLINE, EMBASE, and the Cochrane Library will be searched using common keywords (inception to July 2019) by 2 independent evaluators. Inclusion criteria will be patients with gastrointestinal diseases, DNI measurements performed in the emergency department, indices of diagnostic performance (sensitivity, specificity, predictive values, and likelihood ratios) of DNI for predicting severity, surgical outcomes, and mortality rate of gastrointestinal diseases. True and false positives and negatives will be calculated based on the diagnostic indices of each study. All types of study designs with full-text literature written in English will be included. Risk of bias will be assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Descriptive data synthesis will be conducted and quantitative synthesis (bivariate and hierarchical summary receiver operating characteristic model) will be performed if the included studies are sufficiently homogenous. Meta-regression, sensitivity analysis, publication bias, and Fagan nomogram will be analyzed and described. RESULTS: The pooled synthesis of the diagnostic performance of various gastrointestinal diseases with different cut-off values for DNI may limit the interpretation of uniform diagnostic validity. The authors will contact the corresponding authors for the missing values, requesting the original data in each study. However, if there are no responses from these authors, these studies will be excluded. CONCLUSION: This study will provide diagnostic validity of DNI as an initial marker for the prediction of severity, surgery, and mortality of gastrointestinal diseases.


Assuntos
Gastroenteropatias/sangue , Gastroenteropatias/mortalidade , Neutrófilos/metabolismo , Biomarcadores , Gastroenteropatias/cirurgia , Humanos , Prognóstico , Projetos de Pesquisa , Sensibilidade e Especificidade , Índice de Gravidade de Doença
4.
Chem Biodivers ; 16(8): e1900204, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31298500

RESUMO

The purpose of this work was to determine the chemical composition and evaluate the antichemotactic, antioxidant, and antifungal activities of the essential oil obtained from the species Cryptocarya aschersoniana Mez, Cinnamomum amoenum (Ness & Mart.) Kosterm., and Schinus terebinthifolia Raddi, as well as the combination of C. aschersoniana essential oil and terbinafine against isolates of dermatophytes. Allo-aromadendrene, bicyclogermacrene, and germacrene B were identified as major compounds in essential oils. The essential oil of C. aschersoniana shown 100 % inhibitory effect on leukocyte migration at the concentration of 10 µg/mL while S. terebinthifolia oil presented 80.1 % inhibitory effect at the same concentration. Only S. terebinthifolia oil possessed free-radical-scavenging activity which indicates its antioxidant capacity. The essential oils were also tested against fungal isolates of dermatophyte species (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis and Microsporum gypseum), resulting in MIC ranging from 125 µg/mL to over 500 µg/mL. C. aschersoniana oil combined with terbinafine resulted in an additive interaction effect. In this case, the essential oil may act as a complement to conventional therapy for the topical treatment of superficial fungal infections, mainly because it is associated with an anti-inflammatory effect.


Assuntos
Anacardiaceae/química , Antifúngicos/química , Cinnamomum/química , Cryptocarya/química , Óleos Voláteis/química , Anacardiaceae/metabolismo , Antifúngicos/farmacologia , Antioxidantes/química , Candida/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Cinnamomum/metabolismo , Cryptocarya/metabolismo , Testes de Sensibilidade Microbiana , Microsporum/efeitos dos fármacos , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Óleos Voláteis/farmacologia , Extratos Vegetais/química , Trichophyton/efeitos dos fármacos
5.
Artigo em Chinês | MEDLINE | ID: mdl-31327190

RESUMO

Objective:The aim of this study is to explore the expression of ECP in the neutrophils and its impact on the evaluation of nasal inflammation.Method:Neutrophils and eosinophils in nasal secretions were collected and stained with ECP immunohistochemistry to observe the staining of ECP in different cells. The concentration of ECP and MPO in nasal secretion were detected of 32 patients with allergic rhinitis (AR group), 29 patients with chronic rhinosinusitis without nasal polyps and allergic rhinitis (CRSsNP group), and 21 healthy people (control group). The percentage of neutrophils and eosinophils were calculated and analyzed as well.Result:ECP could be found in both eosinophils and neutrophils with immunohistochemical staining. The expression of ECP is much stronger in eosinophils than that in neutrophils. The ECP and MPO concentration in the nasal secretions of AR group and CRSsNP group were significantly higher than that in control group (P<0.000 1), and the ECP concentration in AR group and CRSsNP group had no difference. The expression of ECP in the AR group was not different from that in CRSsNP group, but the expression of MPO was significantly lower than that in CRSsNP group(P<0.000 1).Conclusion:ECP is expressed in neutrophils, and which is likely to have influence on the objective evaluation to nasal inflammation. Combining with the expression of ECP and MPO, we can make a more accurate judgment of local inflammation.


Assuntos
Proteína Catiônica de Eosinófilo/metabolismo , Inflamação/fisiopatologia , Mucosa Nasal/patologia , Neutrófilos/metabolismo , Estudos de Casos e Controles , Eosinófilos , Humanos , Inflamação/diagnóstico , Peroxidase/metabolismo , Rinite Alérgica/fisiopatologia , Rinosporidiose , Sinusite/fisiopatologia
6.
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
7.
Food Chem Toxicol ; 131: 110577, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31220534

RESUMO

Cadmium and aflatoxin B1 (AFB1) are both common and widespread pollutants in food and feed. There are several reports on toxicity induced by Cadmium or AFB1 alone, but few address the toxicity caused by co-exposure to the two substances. In this study, 42 female and 42 male Kunming (KM) mice were divided into seven groups to test the acute oral toxicity of CdCl2 and AFB1, using Karber's method. The combined toxicity was assessed using the Keplinger evaluation system. Acute toxicity symptoms, deaths, and body and organ weights were evaluated, and hematological, blood biochemical, and histopathological analyses were conducted. The results revealed the following median lethal doses (LD50): LD50(Female KM mice) = 62.56 mg/kg; LD50(Male KM mice) = 48.79 mg/kg; LD50(KM mice)=55.27 mg/kg. The combined toxicity of AFB1 and CdCl2 showed an additive effect in mice, and an increase in the mixed dose of AFB1 and CdCl2 resulted in greater toxicity. These results demonstrated that the combined toxicity of AFB1 and CdCl2 was greater than the toxicities of the individual components in mice; thus, this may cause particular challenges when addressing these hazards in food and feed and the associated risk to human and animal health.


Assuntos
Aflatoxina B1/toxicidade , Cádmio/toxicidade , Administração Oral , Aflatoxina B1/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Cádmio/administração & dosagem , Eosinófilos/metabolismo , Feminino , Rim/patologia , Contagem de Leucócitos , Fígado/patologia , Masculino , Camundongos , Neutrófilos/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Testes de Toxicidade Aguda
8.
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
9.
Cell Mol Life Sci ; 76(16): 3097-3116, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172218

RESUMO

Metalloproteinases-such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs)-are involved in various diseases of the nervous system but also contribute to nervous system development, synaptic plasticity and neuroregeneration upon injury. MMPs and ADAMs proteolytically cleave many substrates including extracellular matrix components but also signaling molecules and receptors. During neuroinfectious disease with associated neuroinflammation, MMPs and ADAMs regulate blood-brain barrier breakdown, bacterial invasion, neutrophil infiltration and cytokine signaling. Specific and broad-spectrum inhibitors for MMPs and ADAMs have experimentally been shown to decrease neuroinflammation and brain damage in diseases with excessive neuroinflammation as a common denominator, such as pneumococcal meningitis and multiple sclerosis, thereby improving the disease outcome. Timing of metalloproteinase inhibition appears to be critical to effectively target the cascade of pathophysiological processes leading to brain damage without inhibiting the neuroregenerative effects of metalloproteinases. As the critical role of metalloproteinases in neuronal repair mechanisms and regeneration was only lately recognized, the original idea of chronic MMP inhibition needs to be conceptually revised. Recently accumulated research urges for a second chance of metalloproteinase inhibitors, which-when correctly applied and dosed-harbor the potential to improve the outcome of different neuroinflammatory diseases.


Assuntos
Proteínas ADAM/metabolismo , Metaloproteinases da Matriz/metabolismo , Esclerose Múltipla/patologia , Doenças do Sistema Nervoso/patologia , Barreira Hematoencefálica/metabolismo , Citocinas/metabolismo , Humanos , Esclerose Múltipla/metabolismo , Doenças do Sistema Nervoso/metabolismo , Neurônios/metabolismo , Neutrófilos/citologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Transdução de Sinais
10.
Int J Mol Sci ; 20(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075840

RESUMO

Timely and reliable distinction of sepsis from non-infectious systemic inflammatory response syndrome (SIRS) supports adequate antimicrobial therapy and saves lives but is clinically challenging. Blood transcriptional profiling promises to deliver insights into the pathomechanisms of SIRS and sepsis and to accelerate the discovery of urgently sought sepsis biomarkers. However, suitable reference genes for normalizing gene expression in these disease conditions are lacking. In addition, variability in blood leukocyte subtype composition complicates gene profile interpretation. Here, we aimed to identify potential reference genes in natural killer (NK) cells and granulocytes from patients with SIRS and sepsis on intensive care unit (ICU) admission. Discovery by a two-step probabilistic selection from microarray data followed by validation through branched DNA assays in independent patients revealed several candidate reference genes in NK cells including AKIRIN1, PPP6R3, TAX1BP1, and ADRBK1. Initially, no candidate genes could be validated in patient granulocytes. However, we determined highly similar AKIRIN1 expression also in SIRS and sepsis granulocytes and no change by in vitro LPS challenge in granulocytes from healthy donors. Inspection of external neutrophil transcriptome datasets further support unchanged AKIRIN1 expression in human systemic inflammation. As a potential new reference gene in NK cells and granulocytes in infectious and inflammatory diseases, AKIRIN1 may improve our pathomechanistic understanding of SIRS and sepsis and help identifying new sepsis biomarkers.


Assuntos
Proteínas de Ligação a DNA/genética , Granulócitos/metabolismo , Células Matadoras Naturais/metabolismo , Sepse/genética , Sepse/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação/genética , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Padrões de Referência , Reprodutibilidade dos Testes , Síndrome de Resposta Inflamatória Sistêmica/genética , Síndrome de Resposta Inflamatória Sistêmica/patologia , Doadores de Tecidos , Transcriptoma/genética
11.
Pharm Res ; 36(7): 97, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31076925

RESUMO

PURPOSE: The aim of this research was to design dexamethasone palmitate (DP) loaded sialic acid modified liposomes, with the eventual goal of using peripheral blood neutrophils (PBNs) that carried drug-loaded liposomes to improve the therapeutic capacity for rheumatoid arthritis (RA). METHODS: A sialic acid - cholesterol conjugate (SA-CH) was synthesized and anchored on the surface of liposomal dexamethasone palmitate (DP-SAL). The physicochemical characteristics and in vitro cytotoxicity of liposomes were evaluated. Flow cytometry and confocal laser scanning microscopy were utilized to investigate the accumulation of liposomes in PBNs. The adjuvant-induced arthritis was adopted to investigate the targeting ability and anti-inflammatory effect of DP loaded liposomes. RESULTS: Both DP-CL and DP-SAL existed an average size less than 200 nm with remarkably high encapsulation efficiencies more than 90%. In vitro and in vivo experiments manifested SA-modified liposomes provided a reinforced accumulation of DP in PBNs. As well, DP-SAL displayed a greater degree of accumulation in the joints and a stronger anti-inflammatory effect in terms of RA suppression. CONCLUSIONS: SA-modified liposomal DP was a promising candidate for RA-targeting treatment through the neutrophil-mediated drug delivery system.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Dexametasona/farmacocinética , Lipossomos/química , Ácido N-Acetilneuramínico/química , Neutrófilos/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/toxicidade , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Colesterol/química , Dexametasona/administração & dosagem , Dexametasona/toxicidade , Liberação Controlada de Fármacos , Articulações/efeitos dos fármacos , Articulações/patologia , Selectina L/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/patologia , Masculino , Neutrófilos/patologia , Palmitatos/química , Ratos Wistar , Distribuição Tecidual
12.
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
13.
Molecules ; 24(9)2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083328

RESUMO

Organosulfur compounds are bioactive components of garlic essential oil (EO), mustard oil, Ferula EOs, asafoetida, and other plant and food extracts. Traditionally, garlic (Allium sativum) is used to boost the immune system; however, the mechanisms involved in the putative immunomodulatory effects of garlic are unknown. We investigated the effects of garlic EO and 22 organosulfur compounds on human neutrophil responses. Garlic EO, allyl propyl disulfide, dipropyl disulfide, diallyl disulfide, and allyl isothiocyanate (AITC) directly activated Ca2+ flux in neutrophils, with the most potent being AITC. Although 1,3-dithiane did not activate neutrophil Ca2+ flux, this minor constituent of garlic EO stimulated neutrophil reactive oxygen species (ROS) production. In contrast, a close analog (1,4-dithiane) was unable to activate neutrophil ROS production. Although 1,3-dithiane-1-oxide also stimulated neutrophil ROS production, only traces of this oxidation product were generated after a 5 h treatment of HL60 cells with 1,3-dithiane. Evaluation of several phosphatidylinositol-3 kinase (PI3K) inhibitors with different subtype specificities (A-66, TGX 221, AS605240, and PI 3065) showed that the PI3K p110δ inhibitor PI 3065 was the most potent inhibitor of 1,3-dithiane-induced neutrophil ROS production. Furthermore, 1,3-dithiane enhanced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), glycogen synthase kinase 3 α/ß (GSK-3α/ß), and cAMP response element binding (CREB) protein in differentiated neutrophil-like HL60 cells. Density functional theory (DFT) calculations confirmed the reactivity of 1,3-dithiane vs. 1,4-dithiane, based on the frontier molecular orbital analysis. Our results demonstrate that certain organosulfur compounds can activate neutrophil functional activity and may serve as biological response modifiers by augmenting phagocyte functions.


Assuntos
Fatores Imunológicos/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Compostos Orgânicos/farmacologia , Compostos de Enxofre/farmacologia , Compostos Alílicos/farmacologia , Antioxidantes/metabolismo , Dissulfetos/farmacologia , Alho/química , Células HL-60 , Compostos Heterocíclicos/farmacologia , Humanos , Proteínas Quinases Ativadas por Mitógeno , Neutrófilos/metabolismo , Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Quinoxalinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sulfetos/farmacologia , Tiazolidinedionas/farmacologia
14.
Chem Biol Interact ; 308: 45-50, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31095933

RESUMO

The flavonoid hesperidin is abundantly found in citrus fruits and is used to treat vascular diseases. Previous studies described its gastroprotective actions against stress or ethanol-induced ulcer in rodents; however, results from indomethacin-induced ulcer were controversy. Therefore, given its clinical use and contradictory findings in acute models, this study aims to evaluate the effect of hesperidin (1-10 mg/kg, p.o) on chronic gastric ulcer induced by acetic acid in rats, a model that resembles the ulcer in humans. Moreover, the effects of hesperidin on mucin levels and on inflammatory and oxidative parameters at ulcer site were also measured. The treatment with hesperidin at 3 and 10 mg/kg, once a day, by seven days, accelerated by 34 and 62%, respectively, the ulcer healing process when compared to vehicle-treated group (99.1 ±â€¯6.4 mm2). Histological and histochemistry analyses confirmed the healing effect with significant favoring of mucin production. Hesperidin also promoted the preservation of reduced glutathione levels in the gastric mucosa tissue, as well as the normalization of superoxide dismutase and catalase activities at similar levels to those found in the non-ulcerated group. In addition, flavonoid administration increased the enzymatic activity of glutathione-S-transferase by 35%. Tissue lipoperoxides and myeloperoxidase activity were reduced after hesperidin treatment. In conclusion, the flavonoid hesperidin revealed a gastric healing activity in the ulcerated mucosa, an effect that showed to be associated with the reduction of oxidative damage at ulcer site, due to the reduction of the neutrophil migration and the strengthening of the mucus barrier next to the mucosa.


Assuntos
Glicosídeos/uso terapêutico , Hesperidina/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Ácido Acético/toxicidade , Animais , Catalase/metabolismo , Esquema de Medicação , Flavanonas/química , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Glutationa/metabolismo , Glicosídeos/farmacologia , Hesperidina/farmacologia , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo , Cicatrização/efeitos dos fármacos
15.
Int J Mol Sci ; 20(9)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060326

RESUMO

The immunomodulatory effects of mesenchymal stem cells (MSCs) are established. However, the effects of MSCs on neutrophil survival in acute lung injury (ALI) remain unclear. The goal of this study was to investigate the effect of an MSC-conditioned medium (MSC-CM) on neutrophil apoptosis in endotoxin-induced ALI. In this study, an MSC-CM was delivered via tail vein injection to wild-type male C57BL/6 mice 4 h after an intratracheal injection of lipopolysaccharide (LPS). Twenty-four hours later, bronchoalveolar lavage fluid (BALF) and lung tissue were collected to perform histology, immunohistochemistry, apoptosis assay of neutrophil, enzyme-linked immunosorbent assays, and an electrophoretic mobility shift assay. Human neutrophils were also collected from patients with sepsis-induced acute respiratory distress syndrome (ARDS). Human neutrophils were treated in vitro with LPS, with or without subsequent MSC-CM co-treatment, and were then analyzed. Administration of the MSC-CM resulted in a significant attenuation of histopathological changes, the levels of interleukin-6 and macrophage inflammatory protein 2, and neutrophil accumulation in mouse lung tissues of LPS-induced ALI. Additionally, MSC-CM therapy enhanced the apoptosis of BALF neutrophils and reduced the expression of the anti-apoptotic molecules, Bcl-xL and Mcl-1, both in vivo and in vitro experiments. Furthermore, phosphorylated and total levels of nuclear factor (NF)-κB p65 were reduced in lung tissues from LPS + MSC-CM mice. Human MSC-CM also reduced the activity levels of NF-κB and matrix metalloproteinase-9 in the human neutrophils from ARDS patients. Thus, the results of this study suggest that the MSC-CM attenuated LPS-induced ALI by inducing neutrophil apoptosis, associated with inhibition of the NF-κB pathway.


Assuntos
Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Apoptose/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Células-Tronco Mesenquimais/metabolismo , NF-kappa B/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Lesão Pulmonar Aguda/patologia , Animais , Citocinas/metabolismo , Endotoxinas/efeitos adversos , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Neutrófilos/imunologia
16.
J Photochem Photobiol B ; 196: 111511, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129510

RESUMO

Prolonged exposure of the skin to ultraviolet radiation (UV) leads to its damage and loss of protective properties. This condition called photoaging of the skin is caused by a number of destructive factors, such as reactive oxygen species (ROS) and proteolytic enzymes that cause damage to the extracellular matrix, e.g. collagen fibers. Many cells of the immune system, including neutrophils, are involved in the photoaging process. The presence of neutrophils in the skin exposed to UV irradiation is known; however, the mechanism of neutrophil activity at these conditions remains unclear. In our study, we focused on the ability of neutrophils to release neutrophil extracellular traps (NETs) and the role of these structures in the photoaging process. NET release occurs in response to various stimuli; however, we hereby showed that the UVA and UVB radiation that reaches the Earth's surface could activate the mechanism of netosis. UV-induced netosis was much faster than that activated by chemical or biological factors; however, it also occurred due to the production of ROS, known signal mediators in netosis. In this work, we also identified the probable netosis signaling pathway involved in the neutrophil response to UV. The participation of NET components may explain the ongoing process of skin photoaging, but it is also important to indicate netosis as a potential target for skin protection therapy. Antioxidants tested in this work, such as N-acetylcysteine, ethamsylate, as well as vitamin B1 (thiamine), can successfully inhibit UV-induced netosis, and thus be used as protective components against the negative effects of solar radiation.


Assuntos
Armadilhas Extracelulares/metabolismo , Neutrófilos/efeitos da radiação , Raios Ultravioleta , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Células Cultivadas , Armadilhas Extracelulares/química , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Interleucinas/genética , Interleucinas/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neutrófilos/citologia , Neutrófilos/metabolismo , Fosforilação/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Quinase Syk/metabolismo
17.
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
18.
Nat Commun ; 10(1): 2121, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31073183

RESUMO

Pulmonary immune control is crucial for protection against pathogens. Here we identify a pathway that promotes host responses during pulmonary bacterial infection; the expression of CD200 receptor (CD200R), which is known to dampen pulmonary immune responses, promotes effective clearance of the lethal intracellular bacterium Francisella tularensis. We show that depletion of CD200R in mice increases in vitro and in vivo infectious burden. In vivo, CD200R deficiency leads to enhanced bacterial burden in neutrophils, suggesting CD200R normally limits the neutrophil niche for infection. Indeed, depletion of this neutrophil niche in CD200R-/- mice restores F. tularensis infection to levels seen in wild-type mice. Mechanistically, CD200R-deficient neutrophils display significantly reduced reactive oxygen species production (ROS), suggesting that CD200R-mediated ROS production in neutrophils is necessary for limiting F. tularensis colonisation and proliferation. Overall, our data show that CD200R promotes the antimicrobial properties of neutrophils and may represent a novel antibacterial therapeutic target.


Assuntos
Francisella tularensis/patogenicidade , Interações Hospedeiro-Patógeno/imunologia , Glicoproteínas de Membrana/imunologia , Neutrófilos/imunologia , Tularemia/imunologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Francisella tularensis/imunologia , Humanos , Fragmentos Fc das Imunoglobulinas , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Macrófagos/imunologia , Macrófagos/microbiologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neutrófilos/metabolismo , Neutrófilos/microbiologia , Cultura Primária de Células , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Tularemia/microbiologia
19.
Eur J Clin Microbiol Infect Dis ; 38(6): 1123-1128, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31011855

RESUMO

To evaluate the early absolute CD64/CD15/CD45 neutrophil count as a marker of prognosis of sepsis outcome the absolute CD64/CD15/CD45 count was measured by flow cytometry in 65 patients with confirmed or suspected Gram-negative sepsis and organ dysfunction. Serum interleukin(IL)-8 and interferon-gamma (IFNγ) were measured by an enzyme immunoassay. An absolute count lower than 2500 cells/mm3 could early discriminate non-survivors with sensitivity 82.9% (OR 3.46, 95%CIs 1.10-10.95, p 0.042). After forward step-wise Cox- regression analysis, it was found that acute coagulopathy, acute renal injury, and an early absolute CD64/CD15/CD45 count lower than 2500/mm3 were independently associated with unfavorable outcome. The OR for death among patients with an absolute CD64/CD15/CD45 neutrophil count greater than 2500/mm3 and circulating IL-8 greater than 95 pg/ml was 0.44; this was significantly increased to 7.44 among patients with an absolute CD64/CD15/CD45 neutrophil count lower than 2500/mm3 (p 0.045 by the Breslow-Day's test; p 0.046 by the Tarone's test). An absolute CD64/CD15/CD45 count below 2500/mm3 can be a useful prognosticator of sepsis outcome and a probable indicator of sepsis immunosuppression.


Assuntos
Infecções por Bactérias Gram-Negativas/diagnóstico , Neutrófilos/metabolismo , Receptores de IgG/sangue , Sepse/diagnóstico , Idoso , Biomarcadores/sangue , Feminino , Citometria de Fluxo , Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Negativas/mortalidade , Humanos , Interleucina-8/sangue , Antígenos Comuns de Leucócito/sangue , Antígenos Comuns de Leucócito/metabolismo , Contagem de Leucócitos , Antígenos CD15/sangue , Antígenos CD15/metabolismo , Masculino , Razão de Chances , Escores de Disfunção Orgânica , Prognóstico , Estudos Prospectivos , Receptores de IgG/metabolismo , Sepse/sangue , Sepse/mortalidade , Análise de Sobrevida
20.
Methods Mol Biol ; 1979: 9-21, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31028629

RESUMO

The starting material for all single-cell protocols is a cell suspension. The particular functions and spatial distribution of immune cells generally make them easy to isolate them from the tissues where they dwell. Here we describe tissue dissociation protocols that have been used to obtain human immune cells from lymphoid and nonlymphoid tissues to be then used as input to single-cell methods. We highlight the main factors that can influence the final quality of single-cell data, namely the stress signatures that can bias its interpretation.


Assuntos
Perfilação da Expressão Gênica/métodos , RNA/genética , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Manejo de Espécimes/métodos , Fracionamento Celular/métodos , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Pulmão/citologia , Pulmão/metabolismo , Linfonodos/citologia , Linfonodos/metabolismo , Neutrófilos/citologia , Neutrófilos/metabolismo , RNA/sangue , RNA/isolamento & purificação , Pele/citologia , Pele/metabolismo , Baço/citologia , Baço/metabolismo
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