Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.688
Filtrar
1.
Chem Biol Interact ; 324: 109093, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32298659

RESUMO

Polycystic Ovary Syndrome (PCOS), as a common endocrine disorder is accompanied by hyperandrogenism, insulin resistance, ovulation problems, and infertility. Various types of off-label drugs like metformin have been used for the management of targeted problems caused by PCOS such as insulin resistance and hyperandrogenism. Nicotinamide (NAM) acts as a substrate of visfatin and Nicotinamide N-Methyltransferase (NNMT) leading to the generation of Nicotinamide Adenine Dinucleotide (NAD) and N1-Methylnicotinamide (MNAM), respectively. MNAM is known as an anti-inflammatory, anti-thrombosis, and anti-diabetic agent. In this study, the effects of NAM and MNAM on metabolic and endocrine abnormalities were evaluated in the adipose and ovarian tissues of a letrozole-induced rat model of PCOS. Our results showed that MNAM and NAM reversed abnormal estrous cycle and reduced the serum testosterone levels and CYP17A1 gene expression. Furthermore, all therapeutic factors improved HOMA-IR after treatment and NAM significantly increased the expression of GLUT4 and decreased the gene expression of visfatin. Also, MNAM diminished the gene expression of visfatin and resistin. It is noteworthy that all the therapeutic factors successfully activated the AMPK. In summary, this study is the first study reported beneficial effects of NAM and MNAM on the treatment of PCOS. Additionally, the alleviative effects of our therapeutic factors may be partially mediated by the AMPK-dependent manner due to the contribution of the AMPK in the expression of CYP17A1, visfatin, resistin, and GLUT4. Although more studies are required to unravel the exact mode of actions of MNAM and NAM in the PCOS, the findings of the current study shed light on an urgent need for discovering novel therapeutic pharmaceuticals regarding the treatment of PCOS.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Citocinas/genética , Citocinas/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Hiperandrogenismo/tratamento farmacológico , Hormônio Luteinizante/metabolismo , Metformina/uso terapêutico , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Ratos Wistar , Resistina/genética , Resistina/metabolismo , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Testosterona/metabolismo
2.
Asian Pac J Cancer Prev ; 21(3): 599-609, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32212784

RESUMO

BACKGROUND: Adipokines play an important role in the regulation of inflammation and tumor progression. AIM: Assessment of the possible role of adiponectin, leptin and visfatin in HCV associated hepatocellular carcinoma (HCC). METHODS: patients were classified into 85 patients with HCV associated HCC, 100 patients with chronic hepatitis C viral (HCV) infection compared to 50 normal control (NC) subjects. All subjects included in the study were assessed for HCV infection by seropositive HCV antibodies, as well as HCV RNA by RT-PCR. Serum levels of adiponectin, leptin and visfatin were assessed using enzyme linked immunosorbent assay (ELISA). The data were correlated to the relevant clinic-pathological features of the patients, and the overall survival (OS) rate. RESULTS: There was a significant difference in the serum levels of adiponectin and visfatin among HCC, HCV and NC groups (P<0.001). The serum levels of leptin and alpha fetoprotein (AFP) were significantly higher in HCC group (P<0.001). There was a significant association between the serum level of adiponectin and advanced Child class liver cirrhosis (P=0.03), as well as with poor performance status (ECOG, P=0.02). Serum leptin associated significantly with the number of lesions in the liver (P=0.006), visfatin associated with increased mortality rate (P<0.001). Adiponectin, leptin and visfatin associated significantly with liver cirrhosis in HCV patients (P<0.01). Leptin achieved the highest sensitivity (98.8%). visfatin achieved the highest specificity (100%) and PPV (100%) for detection of HCC. The combination of serum leptin and visfatin for the diagnosis of HCV associated HCC showed sensitivity, specificity, PPV, NPV and accuracy (100%, 96.6%, 93.4%, 100% and 97.4%; respectively). CONCLUSION: Adiponectin, leptin and visfatin have an important role(s) in the pathogenesis of HCV associated HCC. 
.


Assuntos
Adipocinas/metabolismo , Carcinoma Hepatocelular/metabolismo , Hepatite C/complicações , Neoplasias Hepáticas/metabolismo , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/virologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/sangue
3.
Adv Clin Exp Med ; 29(1): 79-84, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32017476

RESUMO

BACKGROUND: Visfatin is one of the pro-inflammatory adipokines secreted by adipose tissue cells. Recent scientific research has drawn attention to the role of adipokines in the pathophysiology of metabolic disorders and their association with inflammatory diseases, including psoriasis. Visfatin may be one of the important links explaining the connection between psoriasis and diseases which are components of metabolic syndrome. OBJECTIVES: The aim of this study was to assess the serum visfatin concentration in patients with psoriasis and to evaluate its possible correlations with parameters of metabolic syndrome and the clinical severity of psoriasis. MATERIAL AND METHODS: A group of 102 patients with psoriasis and a control group of 40 healthy subjects were examined. The clinical severity of psoriasis was assessed according to Psoriasis Area and Severity Index), BSA (Body Surface Area) and DLQI (Dermatology Life Quality Index) indicators, the presence and type of obesity, and hypertension. In both the study and control groups, laboratory tests (C-reactive protein (CRP), glucose concentration, total cholesterol, low-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein (HDL) cholesterol, and triglycerides (TG)) were performed and serum visfatin concentrations were determined. The clinical data, results of laboratory tests and visfatin concentrations were then subjected to statistical analysis. RESULTS: There was a significantly higher concentration of visfatin in the psoriatic patients (p < 0.001) than in the control group. Significant positive correlations between visfatin concentration and PASI (p = 0.008) and BSA (p = 0.007) were observed. In the psoriatic group, there were positive correlations between the concentrations of visfatin and the concentrations of CRP (p = 0.008) and total cholesterol (p = 0.002). Visfatin concentration was elevated in the psoriatic patients who had elevated total cholesterol (p = 0.001), LDL cholesterol (p = 0.012) and TG levels (p = 0.001) compared to the psoriatic patients with normal levels of these lipid profile components. CONCLUSIONS: The results indicate the possible participation of visfatin in pathophysiological and inflammatory processes in the course of psoriasis. Adipokines may be an important link connecting psoriasis with coexisting metabolic disorders.


Assuntos
Síndrome Metabólica , Nicotinamida Fosforribosiltransferase , Psoríase , Estudos de Casos e Controles , HDL-Colesterol , Humanos , Masculino , Síndrome Metabólica/metabolismo , Nicotinamida Fosforribosiltransferase/sangue , Obesidade/metabolismo , Psoríase/metabolismo
4.
PLoS One ; 15(1): e0227459, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31935230

RESUMO

Hepatocellular carcinoma (HCC) is the most common liver cancer, accountable for 90% cases. Visfatin and vaspin are adipocytokines with various suggested functions and proven significant correlations between BMI and percentage of body fat. The aim was to assess visfatin and vaspin serum levels in HCC patients and controls, compare their levels in patients with different cancer etiology and grade assessed according to the Barcelona-Clinic Liver Cancer (BCLC) staging system. The additional aim was to analyze relationship between analyzed adipokines and metabolic abnormalities and liver disfunction severity. The study was performed on 69 cirrhotic patients (54 males/15 females) with HCC, aged 59.0 ± 12.1 years, and with BMI 29.0 ± 4.5 kg/m2 compared to 20 healthy volunteers. Serum visfatin and vaspin concentrations were significantly increased in HCC patients compared to controls (p = 0.01 and p = 0.02, respectively). Serum vaspin was significantly higher in HCC patients with viral compared to those with non-viral etiology (p = 0.02), with more evident increase in chronic hepatitis C patients (CHC). Serum visfatin levels were significantly higher in patients with higher insulin resistance (p = 0.04) and with platelets count > 100 000/mm3 (p<0.001). Patients with BMI >30 kg/m2 had markedly up-regulated vaspin levels (p = 0.04). There was no difference in vaspin and visfatin serum levels with respect to liver dysfunction and BCLC classification. In conclusion, our study revealed serum vaspin and visfatin to be significantly increased in HCC patients independently of cancer etiology compared to controls. Additionally, serum vaspin was elevated in viral disease, especially in CHC. Vaspin up-regulation can be a compensatory mechanism against IR in HCC patients. Serum visfatin and vaspin, although up-regulated, seem not to be associated with cancer grade and cirrhosis severity.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Nicotinamida Fosforribosiltransferase/sangue , Serpinas/sangue , Idoso , Índice de Massa Corporal , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/complicações , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Resistência à Insulina , Cirrose Hepática/complicações , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Contagem de Plaquetas
5.
Eur J Endocrinol ; 182(1): 67-77, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31705791

RESUMO

Objective: Adipokines could be a link between metabolic syndrome (MS) and infertility. While the association between circulating adipokines and fertility has been extensively studied in females, this relationship in males was less investigated, although some adipokines are detectable in seminal plasma (SP). The aim of this study was to determine adipokine levels in blood and SP and to assess the relationships between adipokines, MS and semen parameters in men from infertile couples. Design: Male partners of infertile couples referred to four medical French centers were enrolled in years 2013-2016. Methods: Subjects (n = 160) aged 18-45 years were assessed for anthropometric, biochemical, sperm, and circulating hormonal parameters. Leptin, adiponectin, resistin, chemerin, visfatin, and IL-6 were measured in serum and SP. Results: Infertility duration was higher in men with than without MS. Adipokine concentrations were higher in blood than in SP, except for IL-6 and visfatin. The most striking result was the significant correlation observed between seminal IL-6 and spermatozoid concentration, progressive motility, and sperm vitality. Moreover, while men with MS exhibited an expected lower adiponectinemia, they displayed 2.1-fold higher adiponectin levels in SP than men without MS. Finally, logistic regression analysis showed that BMI, infertility duration, and adiponectin serum/SP ratio were independently associated with MS. Conclusions: These results suggest an involvement of seminal adipokines to modulate fertility in men with MS and that seminal IL-6 could play a beneficial role on sperm functionality. Further mechanistic studies are necessary to investigate the precise roles of these adipokines in male reproduction.


Assuntos
Adipocinas/metabolismo , Infertilidade Masculina/metabolismo , Infertilidade Masculina/fisiopatologia , Adipocinas/sangue , Adolescente , Adulto , Quimiocinas/sangue , Quimiocinas/metabolismo , Feminino , Humanos , Interleucina-6/sangue , Interleucina-6/metabolismo , Leptina/sangue , Leptina/metabolismo , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/sangue , Nicotinamida Fosforribosiltransferase/metabolismo , Reprodução/fisiologia , Sêmen/metabolismo , Sêmen/fisiologia , Contagem de Espermatozoides , Motilidade Espermática/fisiologia , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Adulto Jovem
6.
Biosci Biotechnol Biochem ; 84(3): 544-551, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31791192

RESUMO

Alveolar and bronchial epithelial cells have critical functions in acute respiratory distress syndrome progress. Genistein could protect the lungs from acute lung injury, however, whether genistein protects the alveolar epithelial cells from LPS-induced injury was less studied. Spectrophotometric method 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and enzyme-linked immunosorbent assay (ELISA) were performed to detect cell viability and levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6. Flow cytometry and western blot assay were performed to detect cells apoptosis and protein levels. In LPS-induced model of mouse lung epithelial (MLE)-12 cells, PBEF (proinflammatory cytokine) expression, and cell apoptosis were increased and cell viability was decreased, whereas NF-κB was activated and expression levels of TNF-α, IL-1ß, and IL-6 were increased. However, genistein partly reversed the effect of LPS, and it plays a protective role in lung injury by reducing expression of PBEF, inhibiting the activation of NF-κB and alleviating inflammatory response of cells.


Assuntos
Células Epiteliais/efeitos dos fármacos , Genisteína/farmacologia , Lipopolissacarídeos/toxicidade , Pneumonia/prevenção & controle , Alvéolos Pulmonares/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quimiocinas/metabolismo , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/metabolismo , Camundongos , NF-kappa B/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/patologia
7.
Am J Cardiol ; 125(3): 415-419, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31785772

RESUMO

Visfatin is an adipokine produced by visceral fat tissue and takes part in fibrosis and inflammatory response. In the heart muscle, it is connected with the progression of atherosclerosis. Currently, there is no data on how visfatin affects atrial fibrillation (AF) onset. The study aimed to establish if baseline visfatin levels are connected with the risk of arrhythmia recurrence after AF ablation. In this prospective, long-term, observational study, we enrolled 290 consecutive patients admitted for AF ablation. All patients were screened for cardiovascular risk factors and had blood serum taken to measure visfatin concentrations before the ablation procedure. The end point of the study was a recurrence of the AF, defined as at least one AF episode of at any moment during the follow-up period. The screening included AF of at least 30 second duration assessed with electrocardiogram (ECG) monitoring, including 24-hour ECG Holter monitoring, implantable pacemakers, implantable defibrillators, or subcutaneous ECG monitoring devices. After excluding patients disqualified from the procedure the study population consisted of 236 patients, mean age 57.8 years (64.8% male). Mean body mass index in the population was 29.6 ± 4.8 kg/m2 and arterial hypertension was highly prevalent (73.3% of patients). In 129 (54.7%) cases we observed recurrence of AF during the follow-up period. Patients with AF recurrence had higher visfatin levels (1.7 ± 2.4 vs 2.1 ± 1.9 ng/ml; p <0.0001) and multivariate logistic regression analysis containing age, sex, and other independent variables showed that patients with elevated visfatin levels were almost 3-time more likely to experience AF recurrence (odds ratio 2.92; 95% confidence interval 1.60 to 5.32). In conclusion, patients with higher visfatin levels are at elevated risk of arrhythmia recurrence after ablation for AF. Visfatin can be a useful marker for risk stratification in this group of patients.


Assuntos
Fibrilação Atrial/sangue , Ablação por Cateter , Nicotinamida Fosforribosiltransferase/sangue , Fibrilação Atrial/cirurgia , Biomarcadores/sangue , Eletrocardiografia Ambulatorial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Recidiva , Fatores de Risco
8.
Phytother Res ; 34(4): 859-866, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31849123

RESUMO

Pemphigus vulgaris (PV) is a chronic autoimmune disorder with potentially fatal outcomes. The aim of this study was to investigate the effect of l-carnitine (LC) on secreted frizzled-related protein-5 (SFRP5), omentin, visfatin, and glycemic indices in PV patients under corticosteroid treatment. In this randomized, double-blind, placebo-controlled clinical trial, 52 patients with PV were divided randomly into two groups to receive 2 g of LC or a placebo for 8 weeks. Serum levels of SFRP5, omentin, visfatin, and also glycemic indices were evaluated at the baseline and end of the study. LC supplementation significantly decreased the serum level of visfatin (95% CI [-14.718, -0.877], p = .05) and increased the serum levels of SFRP5 (95%CI [1.637, 11.380], p < .006) and omentin (95% CI [9.014, 65.286], p < .01). However, LC supplementation had no significant effects on the serum levels of glycemic factors such as insulin (95% CI [-1.125, 3.056], p = .426), fasting blood sugar (95% CI [-4.743, 3.642], p = .894), homeostatic model assessment of insulin resistance (95% CI [-0.305, 0.528], p = .729), and quantitative insulin-sensitivity check index (95% CI [-0.016, -0.010], p = .81). LC supplementation decreased visfatin serum level and increased omentin-1 and SFRP5 serum levels in patients with PV. However, it has no significant effect on the serum levels of insulin and glycemic indices.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/sangue , Glicemia/efeitos dos fármacos , Carnitina/farmacologia , Citocinas/sangue , Lectinas/sangue , Nicotinamida Fosforribosiltransferase/sangue , Pênfigo/tratamento farmacológico , Adulto , Idoso , Glicemia/metabolismo , Carnitina/uso terapêutico , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Proteínas Ligadas por GPI/sangue , Indicadores Básicos de Saúde , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Pênfigo/sangue , Pênfigo/metabolismo , Placebos
9.
Lipids Health Dis ; 18(1): 221, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836012

RESUMO

BACKGROUND: Lipids and adipokines including leptin, resistin and visfatin play various roles in the pathophysiology of Gestational Diabetes Mellitus (GDM). This study was aimed at determining whether serum leptin, resistin and visfatin are significantly altered during the first trimester of pregnancies that subsequently develop GDM and whether such changes are useful in predicting the disease. METHODS: This was a case-case control study which compared first trimester biochemical and anthropometric parameters in 70 pregnant women who subsequently developed GDM and 70 pregnant women without GDM at the Volta Regional Hospital, Ho, Ghana. Lipid profile and some selected adipokines were analyzed and first trimester body mass index (BMI) was determined. RESULTS: There were significant differences (p < 0.05) in leptin, resistin, and visfatin as well as significant dyslipidemia among those with GDM compared to those without GDM. Furthermore, the area under the Receiver Operating Characteristic Curves (AUCs) for leptin, resistin and visfatin were; 0.812, 0.836 and 0.799 respectively. Increased first trimester leptin (OR = 1.166; CI = 1.104-1.233; p < 0.0001), resistin (p < 0.0001) and visfatin (p < 0.0001) were associated with GDM. CONCLUSION: Hyperleptinemia, hyperesistinemia and hypervisfatinemia precede GDM and can serve as good predictive indices for gestational diabetes mellitus.


Assuntos
Diabetes Gestacional/sangue , Leptina/sangue , Nicotinamida Fosforribosiltransferase/sangue , Resistina/sangue , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Lipídeos/sangue , Gravidez , Primeiro Trimestre da Gravidez
10.
Anticancer Res ; 39(12): 6457-6462, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810909

RESUMO

BACKGROUND/AIM: Nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in the NAD+ biosynthetic pathway, is a drug target of potent anticancer candidates, including FK866 and other reported NAMPT inhibitors. However, it is known that NAMPT point-mutations render resistance to specific NAMPT inhibitors in several cancer cells. We investigated the resistance mechanisms of NAMPT inhibitor FK866 in human colorectal cancer (CRC) cells. MATERIALS AND METHODS: We used CRC human cell line HCT116 to determine the expression profiles of FK866-sensitive parental HCT116 cells and FK866-resistant HCT116 (HCT116RFK866) cells by DNA microarray analysis. The levels of multidrug resistance protein 1 (MDR1) were assessed via western blot. In addition, we analyzed the sensitivity of FK866 in parental HCT116 cells and HCT116RFK866 cells by co-treatment with MDR1 inhibitor verapamil. RESULTS: Our results revealed an association between ATP-binding cassette (ABC) transporter gene ABCB1 and resistance to NAMPT inhibitor FK866 in both HCT116RFK866 cells and parental HCT116 cells. The expression of ABCB1, which encodes MDR1, was lower in HCT116RFK866 cells than in parental HCT116 cells. Furthermore, the protein level of MDR1/ATP-binding cassette sub-family B member 1 (ABCB1) was 0.5-fold lower in HCT116RFK866 cells than in parental HCT116 cells. Additionally, HCT116RFK866 cells showed improved sensitivity to FK866 when co-treated with verapamil, an ABCB1 inhibitor. Interestingly, the efficacy of FK866 in parental HCT116 cells was the same for the treatment with FK866 alone or in combination with verapamil. CONCLUSION: The change in expression of ABCB1 plays a key role in CRC drug resistance to NAMPT inhibitor FK866. This suggests that the MDR1/ABCB1 mechanism may regulate the resistance of anticancer NAMPT inhibitor FK866.


Assuntos
Neoplasias Colorretais/genética , Resistencia a Medicamentos Antineoplásicos , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Acrilamidas/farmacologia , Neoplasias Colorretais/metabolismo , Citocinas/antagonistas & inibidores , Regulação para Baixo , Sinergismo Farmacológico , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Piperidinas/farmacologia , Verapamil/farmacologia
11.
Crit Care ; 23(1): 410, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842964

RESUMO

BACKGROUND: There is a compelling unmet medical need for biomarker-based models to risk-stratify patients with acute respiratory distress syndrome. Effective stratification would optimize participant selection for clinical trial enrollment by focusing on those most likely to benefit from new interventions. Our objective was to develop a prognostic, biomarker-based model for predicting mortality in adult patients with acute respiratory distress syndrome. METHODS: This is a secondary analysis using a cohort of 252 mechanically ventilated subjects with the diagnosis of acute respiratory distress syndrome. Survival to day 7 with both day 0 (first day of presentation) and day 7 sample availability was required. Blood was collected for biomarker measurements at first presentation to the intensive care unit and on the seventh day. Biomarkers included cytokine-chemokines, dual-functioning cytozymes, and vascular injury markers. Logistic regression, latent class analysis, and classification and regression tree analysis were used to identify the plasma biomarkers most predictive of 28-day ARDS mortality. RESULTS: From eight biologically relevant biomarker candidates, six demonstrated an enhanced capacity to predict mortality at day 0. Latent-class analysis identified two biomarker-based phenotypes. Phenotype A exhibited significantly higher plasma levels of angiopoietin-2, macrophage migration inhibitory factor, interleukin-8, interleukin-1 receptor antagonist, interleukin-6, and extracellular nicotinamide phosphoribosyltransferase (eNAMPT) compared to phenotype B. Mortality at 28 days was significantly higher for phenotype A compared to phenotype B (32% vs 19%, p = 0.04). CONCLUSIONS: An adult biomarker-based risk model reliably identifies ARDS subjects at risk of death within 28 days of hospitalization.


Assuntos
Biomarcadores/análise , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Medição de Risco/métodos , APACHE , Adulto , Biomarcadores/sangue , Citocinas/análise , Citocinas/sangue , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/análise , Proteína Antagonista do Receptor de Interleucina 1/sangue , Interleucina-1beta/análise , Interleucina-1beta/sangue , Interleucina-6/análise , Interleucina-6/sangue , Interleucina-8/análise , Interleucina-8/sangue , Oxirredutases Intramoleculares/análise , Oxirredutases Intramoleculares/sangue , Análise de Classes Latentes , Modelos Logísticos , Fatores Inibidores da Migração de Macrófagos/análise , Fatores Inibidores da Migração de Macrófagos/sangue , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/análise , Nicotinamida Fosforribosiltransferase/sangue , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/sangue , Síndrome do Desconforto Respiratório do Adulto/sangue , Síndrome do Desconforto Respiratório do Adulto/epidemiologia , Medição de Risco/normas , Receptores de Esfingosina-1-Fosfato/análise , Receptores de Esfingosina-1-Fosfato/sangue , Proteínas de Transporte Vesicular/análise , Proteínas de Transporte Vesicular/sangue
12.
Int J Mol Sci ; 20(22)2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31717318

RESUMO

Granulocyte-colony stimulating factor (G-CSF)/nicotinamide phosphoribosyltransferase (NAMPT) signaling has been shown to be crucial for the modulation of neutrophil development and functionality. As this signaling pathway is significantly suppressed by type I interferons (IFNs), we aimed to study how the regulation of neutrophil differentiation and phenotype is altered in IFN-deficient mice during granulopoiesis. The composition of bone marrow granulocyte progenitors and their Nampt expression were assessed in bone marrow of type I IFN receptor knockout (Ifnar1-/-) mice and compared to wild-type animals. The impact of NAMPT inhibition on the proliferation, survival, and differentiation of murine bone marrow progenitors, as well as of murine 32D and human HL-60 neutrophil-like cell lines, was estimated. The progressive increase of Nampt expression during neutrophil progenitor maturation could be observed, and it was more prominent in IFN-deficient animals. Altered composition of bone marrow progenitors in these mice correlated with the dysregulation of apoptosis and altered differentiation of these cells. We observed that NAMPT is vitally important for survival of early progenitors, while at later stages it delays the differentiation of neutrophils, with moderate effect on their survival. This study shows that IFN-deficiency leads to the elevated NAMPT expression in the bone marrow, which in turn modulates neutrophil development and differentiation, even in the absence of tumor-derived stimuli.


Assuntos
Diferenciação Celular , Interferons/metabolismo , Neutrófilos/citologia , Neutrófilos/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Transdução de Sinais , Animais , Apoptose , Sobrevivência Celular , Fator Estimulador de Colônias de Granulócitos/metabolismo , Células Precursoras de Granulócitos/metabolismo , Células HL-60 , Humanos , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Receptor de Interferon alfa e beta/deficiência , Receptor de Interferon alfa e beta/metabolismo
13.
BMC Cancer ; 19(1): 1027, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675930

RESUMO

BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT) enzyme acts as the major enzyme in the nicotinamide adenine dinucleotide (NAD) synthesis salvage pathway. Deregulation of NAD could be associated with progression of several cancers such as breast cancer. Here, the consequence of NAMPT inhibition by miR-154 was investigated on breast cancer cells. METHODS: MDA-MB-231 and MCF-7 cancer cell lines were transfected with the mimic and inhibitors of miR-154-5p and their corresponding negative controls. Consequently, levels of NAMPT and NAD were assayed employing qRT-PCR, Western blotting and enzymatic method, respectively. Subsequently, flow cytometry and colorimetric methods were performed to evaluate apoptosis and cell viability. Bioinformatics analyses as well as luciferase assay were done to investigate whether the 3'-UTR of NAMPT is directly targeted by miR-154. RESULTS: According to the obtained results, NAMPT was recognized as a target for binding of miR-154 and the levels of this miRNA was inversely associated with both mRNA and protein levels of NAMPT in breast cancer cell lines. Functionally, miR-154 inhibited the NAD salvage pathway leading to a remarkable decrease in cell viability and increased rate of cell death. When breast cancer cells were simultaneously treated with doxorubicin and miR-154 mimic, cell viability was considerably reduced compared to treatment with doxorubicin alone in both cell lines. CONCLUSIONS: It was concluded that the inhibition of NAD production by miR-154 might be introduced as an appropriate therapeutic approach in order to improve breast cancer outcome either alone or in combination with other conventional chemotherapeutic agents.


Assuntos
Neoplasias da Mama/genética , MicroRNAs/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Regiões 3' não Traduzidas/genética , Antineoplásicos Alquilantes/uso terapêutico , Apoptose , Neoplasias da Mama/tratamento farmacológico , Sobrevivência Celular , Biologia Computacional , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Ativação Enzimática/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Nicotinamida Fosforribosiltransferase/genética
14.
Proc Natl Acad Sci U S A ; 116(47): 23822-23828, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31694884

RESUMO

Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme for cellular energy metabolism. The aim of the present study was to determine the importance of brown and white adipose tissue (BAT and WAT) NAD+ metabolism in regulating whole-body thermogenesis and energy metabolism. Accordingly, we generated and analyzed adipocyte-specific nicotinamide phosphoribosyltransferase (Nampt) knockout (ANKO) and brown adipocyte-specific Nampt knockout (BANKO) mice because NAMPT is the rate-limiting NAD+ biosynthetic enzyme. We found ANKO mice, which lack NAMPT in both BAT and WAT, had impaired gene programs involved in thermogenesis and mitochondrial function in BAT and a blunted thermogenic (rectal temperature, BAT temperature, and whole-body oxygen consumption) response to acute cold exposure, prolonged fasting, and administration of ß-adrenergic agonists (norepinephrine and CL-316243). In addition, the absence of NAMPT in WAT markedly reduced adrenergic-mediated lipolytic activity, likely through inactivation of the NAD+-SIRT1-caveolin-1 axis, which limits an important fuel source fatty acid for BAT thermogenesis. These metabolic abnormalities were rescued by treatment with nicotinamide mononucleotide (NMN), which bypasses the block in NAD+ synthesis induced by NAMPT deficiency. Although BANKO mice, which lack NAMPT in BAT only, had BAT cellular alterations similar to the ANKO mice, BANKO mice had normal thermogenic and lipolytic responses. We also found NAMPT expression in supraclavicular adipose tissue (where human BAT is localized) obtained from human subjects increased during cold exposure, suggesting our finding in rodents could apply to people. These results demonstrate that adipose NAMPT-mediated NAD+ biosynthesis is essential for regulating adaptive thermogenesis, lipolysis, and whole-body energy metabolism.


Assuntos
Adaptação Fisiológica , Tecido Adiposo Marrom/metabolismo , Metabolismo Energético , Homeostase , NAD/biossíntese , Termogênese , Tecido Adiposo Marrom/enzimologia , Animais , Caveolina 1/antagonistas & inibidores , Temperatura Baixa , Citocinas/genética , Jejum , Humanos , Camundongos , Camundongos Knockout , Mononucleotídeo de Nicotinamida/administração & dosagem , Nicotinamida Fosforribosiltransferase/genética
15.
Mol Med Rep ; 20(6): 5163-5171, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31702813

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease of the central nervous system that is characterized by progressive cognitive dysfunction and which ultimately leads to dementia. Studies have shown that energy dysmetabolism contributes significantly to the pathogenesis of a variety of aging­associated diseases and degenerative diseases of the nervous system, including AD. One focus of research thus has been how to regulate the expression of nicotinamide phosphoribosyltransferase (NAMPT) to prevent against neurodegenerative diseases. Therefore, the present study used 6­month­old APPswe/PS1ΔE9 (APP/PS1) transgenic mice as early AD mouse models and sought to evaluate nicotinamide adenine dinucleotide (NAD+) and FK866 (a NAMPT inhibitor) treatment in APP/PS1 mice to study NAMPT dysmetabolism in the process of AD and elucidate the underlying mechanisms. As a result of this treatment, the expression of NAMPT decreased, the synthesis of ATP and NAD+ became insufficient and the NAD+/NADH ratio was reduced. The administration of NAD+ alleviated the spatial learning and memory of APP/PS1 mice and reduced senile plaques. Administration of NAD+ may also increase the expression of the key protein NAMPT and its related protein sirtuin 1 as well as the synthesis of NAD+. Therefore, increasing NAMPT expression levels may promote NAD+ production. Their regulation could form the basis for a new therapeutic strategy.


Assuntos
Acrilamidas/antagonistas & inibidores , Doença de Alzheimer/metabolismo , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , NAD/antagonistas & inibidores , Nicotinamida Fosforribosiltransferase/efeitos dos fármacos , Nicotinamida Fosforribosiltransferase/metabolismo , Piperidinas/antagonistas & inibidores , Transdução de Sinais/fisiologia , Acrilamidas/farmacologia , Amiloide/metabolismo , Animais , Comportamento Animal , Citocinas/genética , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , NAD/metabolismo , NAD/farmacologia , Nicotinamida Fosforribosiltransferase/genética , Piperidinas/farmacologia , Sirtuína 1/metabolismo
16.
Taiwan J Obstet Gynecol ; 58(6): 808-813, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31759533

RESUMO

OBJECTIVE: The aim was to determine the role of visfatin (VF) and human fetuin A (AHSG) in the development of gestational diabetes mellitus (GDM) and to explore the association between these variables and adverse outcomes. MATERIALS AND METHODS: We carried out our study on 68 cases of GDM pregnant women and 42 cases of healthy pregnant women, including 56 cases with diet control and 12 cases with insulin treatment. Enzyme-linked immunoassay (ELISA) was used to test the expression levels of VF and AHSG in maternal and umbilical cord serum. Immunohistochemistry (ICH) was used to test the expression level of the VF protein in placental tissue. RESULTS: The expression levels of VF and AHSG in maternal and umbilical cord serum and the expression level of VF in placental tissue in GDM pregnant women were higher than those in healthy pregnant women. The incidence of adverse outcomes in the GDM pregnant women was higher than that in healthy pregnant women, and these differences were statistically significant (P < 0.05). Those who had higher expression levels of VF or AHSG had a higher incidence of adverse outcomes (P < 0.05). CONCLUSION: The expression of VF and AHSG may participate in the development of GDM. A test of VF and AHSG in GDM pregnant women may have some predictive value for the occurrence of adverse outcomes.


Assuntos
Diabetes Gestacional/metabolismo , Sangue Fetal/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Placenta/metabolismo , Complicações na Gravidez , alfa-2-Glicoproteína-HS/metabolismo , Adulto , Biomarcadores/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Recém-Nascido , Gravidez , Resultado da Gravidez , Estudos Retrospectivos
17.
BMC Endocr Disord ; 19(1): 127, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771561

RESUMO

BACKGROUND: We measured the concentrations of the adipocytokines vaspin and visfatin in obese Chinese children. Furthermore, we studied the correlation of these adipocytokines with early-onset metabolic and vascular sequelae among these children. METHODS: A total of 244 children (160 obese and 84 lean) were included in this study. Vaspin and visfatin were detected using enzyme-linked immunosorbent assays. We also assayed other metabolic and cardiovascular parameters. The associations of serum vaspin and visfatin concentrations with metabolic and cardiovascular parameters were determined. RESULTS: We found a significant elevation in the concentrations of vaspin and visfatin in obese children compared to the concentrations in lean children. Additionally, we found a significant positive correlation between visfatin and vaspin levels, as well as inflammatory cell infiltration and markers of endothelial activation, but these factors did not affect insulin resistance in obese children. Multiple regression analyses confirmed that vaspin is the strongest predictor of higher tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), angiotensin-2 (Ang-2), vascular cellular adhesion molecule-1 (VCAM-1), and E-selectin levels. We also found a significant association between visfatin and Ang-2, IL-6, VCAM-1, and E-selectin levels. CONCLUSION: The adipocytokines vaspin and visfatin are significantly interrelated, and both adipocytokines play a role in vascular endothelial function and inflammation.


Assuntos
Citocinas/sangue , Endotélio Vascular/fisiopatologia , Inflamação/patologia , Resistência à Insulina , Nicotinamida Fosforribosiltransferase/sangue , Obesidade/sangue , Serpinas/sangue , Magreza/sangue , Biomarcadores/análise , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Endotélio Vascular/metabolismo , Feminino , Seguimentos , Humanos , Inflamação/sangue , Masculino , Obesidade/epidemiologia , Obesidade/fisiopatologia , Prognóstico , Magreza/epidemiologia , Magreza/fisiopatologia , Fator de Necrose Tumoral alfa/sangue
18.
Pregnancy Hypertens ; 18: 137-140, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31610400

RESUMO

NAMPT is a biomarker for endothelial dysfunction, but its relationship with nitrite (marker of NO formation) and soluble fms-like tyrosine kinase-1 (sFLT-1) has not been previously evaluated in preeclampsia. Therefore, we measured plasma NAMPT and sFLT-1 levels using enzyme immunoassays and plasma nitrite concentrations using an ozone-based chemiluminescence assay. NAMPT was positively correlated to nitrite (r = 0.217; P = 0.034) and inversely related to sFLT-1 (r = -0.340; P = 0.029) in healthy pregnant women, but inversely related to nitrite (r = -0.259; P = 0.035) and positively correlated to sFLT-1 (r = 0.326; P = 0.007) in preeclamptic patients, suggesting that NAMPT inhibits NO formation and interacts with the antiangiogenic factor sFLT-1 in preeclampsia.


Assuntos
Citocinas/sangue , Nicotinamida Fosforribosiltransferase/sangue , Pré-Eclâmpsia/fisiopatologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Óxido Nítrico/sangue , Pré-Eclâmpsia/sangue , Gravidez , Adulto Jovem
19.
Arch Biochem Biophys ; 676: 108155, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31628926

RESUMO

Plasma-activated medium (PAM), which is prepared by non-thermal atmospheric pressure plasma (NTP) irradiation of cell-free medium, has been shown to exhibit tumor-specific cytotoxicity. Since PAM contains reactive oxygen species (ROS) and reactive nitrogen species (RNS), its anticancer effects are considered to be responsible for oxidative stress induced by these reactive molecules. We previously reported that PAM-induced cell death is closely related to energy failure associated with a decrease in intracellular nicotinamide adenine dinucleotide (NAD+) and ATP levels. Nicotinamide phosphoribosyltransferase (NAMPT), which is a rate-limiting enzyme for NAD+ synthesis in the salvage pathway, was shown to be overexpressed in many types of cancer cells. The NAMPT inhibitor FK866 significantly depletes NAD+ and subsequently suppresses cancer cell proliferation. In this study, we examined the effects of FK866 on PAM-induced cytotoxicity using human breast cancer MDA-MB-231 cells. FK866 dose-dependently enhanced PAM-induced cell death in MDA-MB-231 cells. The combination of PAM and FK866 markedly induced intracellular NAD+ and ATP depletion. Knockdown of NAMPT by siRNA increased the cytotoxicity of PAM. The addition of NAD+ mitigated PAM-induced cell death. In addition, cotreatment with PAM and FK866 augmented ROS production and the decrease in intracellular reduced glutathione (GSH) compared to treatment with PAM alone. FK866 had little effect on PAM-induced mitochondrial dysfunction. Furthermore, the combination of PAM and FK866 decreased the level of NADPH, which is required for GSH metabolism, compared with PAM alone. Taken together, we conclude that cotreatment with NAMPT inhibitors is beneficial for anticancer therapy using PAM.


Assuntos
Neoplasias da Mama/patologia , Meios de Cultura/farmacologia , Inibidores Enzimáticos/farmacologia , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Gases em Plasma/farmacologia , Acrilamidas/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Metabolismo Energético/efeitos dos fármacos , Humanos , Cinética , Estresse Oxidativo/efeitos dos fármacos , Piperidinas/farmacologia
20.
Int J Mol Sci ; 20(20)2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31635187

RESUMO

Synovial membrane inflammation actively participate to structural damage during osteoarthritis (OA). Adipokines, miRNA, and oxidative stress contribute to synovitis and cartilage destruction in OA. We investigated the relationship between visfatin, resistin and miRNA in oxidative stress regulation, in human OA synovial fibroblasts. Cultured cells were treated with visfatin and resistin. After 24 h, we evaluated various pro-inflammatory cytokines, metalloproteinases (MMPs), type II collagen (Col2a1), miR-34a, miR-146a, miR-181a, antioxidant enzymes, and B-cell lymphoma (BCL)2 by qRT-PCR, apoptosis and mitochondrial superoxide production by cytometry, p50 nuclear factor (NF)-κB by immunofluorescence. Synoviocytes were transfected with miRNA inhibitors and oxidative stress evaluation after adipokines stimulus was performed. The implication of NF-κB pathway was assessed by the use of a NF-κB inhibitor (BAY-11-7082). Visfatin and resistin significantly up-regulated gene expression of interleukin (IL)-1ß, IL-6, IL-17, tumor necrosis factor (TNF)-α, MMP-1, MMP-13 and reduced Col2a1. Furthermore, adipokines induced apoptosis and superoxide production, the transcriptional levels of BCL2, superoxide dismutase (SOD)-2, catalase (CAT), nuclear factor erythroid 2 like 2 (NRF2), miR-34a, miR-146a, and miR-181a. MiRNA inhibitors counteracted adipokines modulation of oxidative stress. Visfatin and resistin effects were suppressed by BAY-11-7082. Our data suggest that miRNA may represent possible mediators of oxidative stress induced by visfatin and resistin via NF-κB pathway in human OA synoviocytes.


Assuntos
Citocinas/metabolismo , Fibroblastos/patologia , MicroRNAs/genética , NF-kappa B/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Osteoartrite/patologia , Estresse Oxidativo , Resistina/metabolismo , Membrana Sinovial/patologia , Apoptose , Células Cultivadas , Citocinas/genética , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , NF-kappa B/genética , Nicotinamida Fosforribosiltransferase/genética , Osteoartrite/genética , Osteoartrite/metabolismo , Resistina/genética , Transdução de Sinais , Membrana Sinovial/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA