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1.
J Neuroimmunol ; 354: 577532, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33676085

RESUMO

To determine the utility of lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) as risk markers of stroke-associated pneumonia (SAP). We included 331 stroke patients. The plasma levels of LBP (median: 19.4 vs 15.3 µg/mL, P < 0.01) and sCD14 (median: 1.5 vs 1.4 µg/mL, P = 0.04) were elevated in SAP. In multivariate analysis, a higher level of LBP (OR: 1.09, 95%CI: 1.05-1.13), but not sCD14 (OR: 2.16, 0.94-4.97), was associated with SAP. The addition of LBP or sCD14 to the clinical model did not improve its discriminatory ability. Our results suggest the modest value of studied biomarkers for SAP prediction.


Assuntos
Biomarcadores/sangue , Proteínas de Transporte/sangue , Receptores de Lipopolissacarídeos/sangue , Glicoproteínas de Membrana/sangue , Pneumonia/etiologia , Acidente Vascular Cerebral/complicações , Proteínas de Fase Aguda , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/sangue , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/sangue
2.
Nutrients ; 13(2)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498461

RESUMO

Elevated circulating plasma levels of both lipopolysaccharide-binding protein (LBP) and chemerin are reported in patients with obesity, but few studies are available on lifestyle intervention programs. We investigated the association of both LBP and chemerin plasma levels with metabolic syndrome (MetS) outcomes in a lifestyle intervention in children and adolescents with abdominal obesity Methods: Twenty-nine patients enrolled in a randomized controlled trial were selected. The lifestyle intervention with a 2-month intensive phase and a subsequent 10-month follow-up consisted of a moderate calorie-restricted diet, recommendations to increase physical activity levels, and nutritional education. Results: Weight loss was accompanied by a significant reduction in MetS prevalence (-43%; p = 0.009). Chemerin (p = 0.029) and LBP (p = 0.033) plasma levels were significantly reduced at 2 months and 12 months, respectively. At the end of intervention, MetS components were associated with both LBP (p = 0.017) and chemerin (p < 0.001) plasma levels. Conclusions: We describe for the first time a reduction in both LBP and chemerin plasma levels and its association with MetS risk factors after a lifestyle intervention program in children and adolescents with abdominal obesity. Therefore, LBP and chemerin plasma levels could be used as biomarkers for the progression of cardiovascular risk in pediatric populations.


Assuntos
Restrição Calórica , Proteínas de Transporte/sangue , Quimiocinas/sangue , Estilo de Vida , Glicoproteínas de Membrana/sangue , Síndrome Metabólica/metabolismo , Obesidade Abdominal/metabolismo , Proteínas de Fase Aguda , Adolescente , Criança , Exercício Físico , Feminino , Humanos , Masculino , Obesidade Abdominal/dietoterapia , Perda de Peso
3.
Biomed Pharmacother ; 133: 111083, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378979

RESUMO

Apo-A1 is correlated with conditions like hyperlipidemia, cardiovascular diseases, high altitude pulmonary edema and etc. where hypoxia constitutes an important facet.Hypoxia causes oxidative stress, vaso-destructive and inflammatory outcomes.Apo-A1 is reported to have vasoprotective, anti-oxidative, anti-apoptotic, and anti-inflammatory effects. However, effects of Apo-A1 augmentation during hypoxia exposure are unknown.In this study, we investigated the effects of exogenously supplementing Apo-A1-mimetic peptide on SD rats during hypoxia exposure. For easing the processes of delivery, absorption and bio-availability, Apo-A1 mimetic peptide D4F was used. The rats were given 10 mg/kg BW dose (i.p.) of D4F for 7 days and then exposed to hypoxia. D4F was observed to attenuate both oxidative stress and inflammation during hypoxic exposure. D4F improved energy homeostasis during hypoxic exposure. D4F did not affect HIF-1a levels during hypoxia but increased MnSOD levels while decreasing CRP and Apo-B levels. D4F showed promise as a prophylactic against hypoxia exposure.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apolipoproteína A-I/farmacologia , Metabolismo Energético/efeitos dos fármacos , Hipóxia/tratamento farmacológico , Inflamação/prevenção & controle , Pulmão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Apolipoproteínas B/sangue , Proteínas de Transporte/sangue , Modelos Animais de Doenças , Hipóxia/sangue , Hipóxia/complicações , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Inflamação/sangue , Inflamação/etiologia , Pulmão/metabolismo , Masculino , Oxirredução , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
4.
J Med Virol ; 93(4): 2350-2358, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33314206

RESUMO

To evaluate the maternal serum afamin and vitamin E levels in pregnant women with coronavirus disease 2019 (COVID-19) and to investigate their association with composite adverse perinatal outcomes. This prospective, case-control study consisted of 60 pregnant women with COVID-19 infection and 36 age-matched pregnant women without any defined risk factors. Demographic features, laboratory test results, afamin and vitamin E levels were compared between the groups. A receiver operating characteristic (ROC) curve was used to assess the relationship of afamin and vitamin E levels in predicting composite adverse perinatal outcomes. A correlation analysis was performed between afamin and C-reactive protein (CRP) levels in pregnant women with COVID-19. The obstetric complication rate was higher in the COVID-19 group (13.3% vs. 2.8%) (p = .01). Afamin levels were higher and vitamin E levels were lower in the COVID-19 group (p = .02 and p < .001, respectively). Vitamin E levels were lower in the COVID-19 group for the all trimesters (p < .001, p < .001, and p = .004, respectively). Afamin levels were higher in the COVID-19 group for the all trimesters without reaching statistical significance (p > .05). The values in the ROC curves with the best balance of sensitivity/specificity for afamin and vitamin E were 0.424 mg/l (70.6% sensitivity, 44.3% specificity) and 3.150 µg/ml (76.5% sensitivity, 58.2% specificity), respectively. A positive moderate statistically significant correlation was found between afamin and CRP levels (r = .264, p = .009). Higher afamin and lower vitamin E levels may support the elevated oxidative stress in the etiopathogenesis of COVID-19 and the relationship with composite adverse perinatal outcomes.


Assuntos
/sangue , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/virologia , Albumina Sérica Humana/metabolismo , Vitamina E/sangue , Adulto , Proteína C-Reativa/metabolismo , /virologia , Proteínas de Transporte/sangue , Estudos de Casos e Controles , Feminino , Glicoproteínas/sangue , Humanos , Estresse Oxidativo/fisiologia , Gravidez , Resultado da Gravidez , Estudos Prospectivos , Sensibilidade e Especificidade , Turquia/epidemiologia
5.
PLoS One ; 15(8): e0238251, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845921

RESUMO

Although mass spectrometry-based plasma proteomics enables sensitive and large-scale discovery and validation of biomarkers for various diseases, its integrative application to hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) is not well investigated. Therefore, we analyzed albumin- and immunoglobulin G-depleted plasma samples from 148 and 60 patients with HCC and CCA, respectively, using liquid chromatography-tandem mass spectrometry. The algorithm used to measure the content of each protein was the percentage of exponentially modified protein abundance index. From 5320 proteins assayed in plasma, 53 and 25 biomarker candidates were identified for HCC and CCA, respectively. The abundance of six and two HCC markers particularly protruded in stage II and III, respectively, whereas plasma serine protease inhibitor was the sole marker the level of which steadily decreased with CCA progression. From a prognostic facet, we showed candidate markers and their cutoff levels for evaluating probability of tumor recurrence and patient survival period. Combination Kaplan-Meier models showed that HCC stage III or IV and both the content of alpha-2-HS-glycoprotein and apolipoprotein CIII <0.2% exhibited the poorest post-surgical recurrence-free and overall survivals. Furthermore, the content of afamin ≥0.2% played a significant role on the poor prognosis in patients with CCA. Our findings, taken together, characterized novel plasma biomarker signatures in dissecting tumor stages and post-surgical outcomes of HCC and CCA.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína C-III/sangue , Ductos Biliares Intra-Hepáticos/patologia , Proteínas de Transporte/sangue , Feminino , Glicoproteínas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Proteoma/análise , Inibidores de Serino Proteinase/sangue , Albumina Sérica Humana , alfa-2-Glicoproteína-HS/análise
6.
Life Sci ; 258: 118222, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768577

RESUMO

AIMS: We previously reported that fenugreek-derived 4-hydroxyisoleucine ameliorates insulin resistance via regulation of TNF-α converting enzyme (TACE) expression. In the present study, we further investigate the effects and mechanisms of fenugreek on obesity-induced inflammation and insulin signaling in the high-fat diet (HFD)-challenged obese mice. MAIN METHODS: After 12 weeks of HFD intervention, mice were treated with the low or high dosages of fenugreek. Serum levels of glucose, insulin, lipid profile, inflammation cytokines, and adipokines were detected. Macrophage infiltration and adipose tissue morphology were observed. Western blot was conducted to investigate the expressions of inactive rhomboid 2 (iRhom2) and TACE as well as other signaling pathways in subcutaneous adipose tissue. KEY FINDINGS: We showed that fenugreek significantly suppressed body weight gain and fat accumulation in HFD-challenged obese mice. Meanwhile, fasting glucose, insulin, and HOMA-IR in fenugreek-treated mice were remarkably decreased, which were properly explained by fenugreek-induced activation of the insulin receptor signaling pathway. Moreover, the anti-inflammatory properties of fenugreek were shown by the decrease of systemic and local expressions of pro-inflammatory cytokines as well as reduced macrophage infiltration into adipose tissue. Additionally, fenugreek markedly deactivated NF-κB and JNK pathways. Finally, we demonstrated that fenugreek strikingly repressed the transcriptions and expressions of iRhom2 and TACE. SIGNIFICANCE: Fenugreek shows an encouraging and promising property in ameliorating insulin resistance and suppressing inflammation in obesity, which might be realized by fenugreek-mediated inhibition of iRhom2/TACE axis-facilitated TNF-α release from adipocytes.


Assuntos
Proteína ADAM17/antagonistas & inibidores , Proteínas de Transporte/antagonistas & inibidores , Mediadores da Inflamação/antagonistas & inibidores , Resistência à Insulina/fisiologia , Obesidade/tratamento farmacológico , Trigonella , Proteína ADAM17/sangue , Animais , Proteínas de Transporte/sangue , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Inflamação/sangue , Inflamação/tratamento farmacológico , Mediadores da Inflamação/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sementes
8.
Life Sci ; 256: 117893, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32502539

RESUMO

AIMS: To investigate the effect and underlying mechanism of melittin and tripartite motif (TRIM) family in human embryonic lung fibroblast (HELF). MATERIALS AND METHODS: Lentiviral RNA interference vector and lentiviral overexpression vector were constructed and packaged by transfecting 293T cells; the proliferation of HELF was examined using Cell Counting Kit 8; Western blot and qRT-PCR were performed to examine protein and mRNA expression; the interaction with protein phosphatase magnesium-dependent 1A (PPM1A) was examined by Co-immunoprecipitation. KEY FINDINGS: Compared with the control group, the mRNA expression of the TRIM6, TRIM8 and TRIM47 in the IPF group significantly increased. Melittin inhibited the mRNA expression and protein expression levels of TRIM47, the HELF proliferation, the hydroxyproline levels, and the phosphorylation of Smad2/3; the interference of TRIM47 inhibited the protein expression of Vimentin, α-SMA, CTGF, the phosphorylation of Smad2/3 and the synthesis of hydroxyproline; TRIM47 overexpression elevated the phosphorylation of Smad2/3, induced ubiquitination of PPM1A and decreased the expression level of PPM1A, while TRIM47 RNA interference reversed this result. SIGNIFICANCE: Melittin has anti-fibrotic effect in HELF by directly reducing the phosphorylation of Smad2/3 or indirectly reducing the phosphorylation of Smad2/3 by decreasing the expression levels of TRIM47 whose overexpression induces ubiquitination of PPM1A.


Assuntos
Proteínas de Transporte/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Pulmão/embriologia , Meliteno/farmacologia , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Transdução de Sinais , Actinas/metabolismo , Proteínas de Transporte/sangue , Proliferação de Células/efeitos dos fármacos , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Fibroblastos/efeitos dos fármacos , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hidroxiprolina/metabolismo , Proteínas de Neoplasias/sangue , Proteínas Nucleares/sangue , Fosforilação/efeitos dos fármacos , Proteína Fosfatase 2C/metabolismo , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Ubiquitinação/efeitos dos fármacos , Vimentina/metabolismo
9.
Am J Clin Nutr ; 111(6): 1150-1158, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32393980

RESUMO

BACKGROUND: Saturated-fat intake and endotoxemia can impair cognition. However, their acute impact on cognitive performance is unknown. OBJECTIVE: This study assessed the impact of 2 high-fat meals and endotoxemia on attention. METHODS: In this double-blind, randomized crossover trial, 51 women (n = 32 breast cancer survivors, n = 19 noncancer controls; mean ± SD age: 53 ± 8 y) completed the Continuous Performance Test (CPT) and had their blood drawn to assess endotoxemia markers LPS binding protein (LBP), soluble CD14 (sCD14), and the LBP to sCD14 ratio 1 h prior to eating either a high-saturated-fat meal or a high-oleic-sunflower-oil meal. Women again completed the CPT 5 h postmeal. At 1 to 4 wk later, women completed the same protocol but consumed the other meal. RESULTS: In adjusted models, women had more difficulty distinguishing target stimuli from distractors after consuming the high-saturated-fat meal than they did after the oleic-sunflower-oil meal (B = 4.44, SE = 1.88, P = 0.02). Women with higher baseline LBP had less consistent response times (B = 0.002, SE = 0.0008, P = 0.04). Those with higher LBP and LBP:sCD14 were less able to sustain their attention throughout the entire CPT, as reflected by their progressively slower (B = 0.002, SE = 0.0006, P = 0.003; and B = 2.43, SE = 0.090, P = 0.008, respectively) and more erratic (B = 0.003, SE = 0.0008, P < 0.0001; and B = 3.29, SE = 1.17, P = 0.006, respectively) response times. Additionally, women with higher baseline LBP or sCD14 were less able to maintain or increase response speeds at higher interstimulus intervals (B = 0.002, SE = 0.0006, P = 0.02; and B = 0.006, SE = 0.003, P = 0.03, respectively), indicating greater difficulty adapting to changing task demands. Significant meal type by LBP and LBP:sCD14 interactions emerged (P < 0.05), such that high LBP and LBP:sCD14 erased between-meal cognitive differences, uniformly impairing performance. CONCLUSIONS: These results suggest that higher LBP, sCD14, and LBP:sCD14 and saturated-fat intake individually and jointly influence attention. Endotoxemia may override the relative cognitive benefit of healthier oil choices.This trial is registered at clinicaltrials.gov as NCT04247763.


Assuntos
Endotoxemia/psicologia , Proteínas de Fase Aguda , Adulto , Idoso , Atenção , Proteínas de Transporte/sangue , Cognição , Dieta Hiperlipídica/psicologia , Método Duplo-Cego , Endotoxemia/sangue , Endotoxemia/metabolismo , Feminino , Humanos , Receptores de Lipopolissacarídeos/sangue , Masculino , Refeições/psicologia , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Período Pós-Prandial
10.
J Pediatr Endocrinol Metab ; 33(2): 265-270, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31953997

RESUMO

Background The relationship between cytokines and lipid metabolism has garnered attention given their potential metabolic interaction. However, the relationship between adropin and lipopolysaccharide-binding protein (LBP) and obesity-related inflammation has not been reported, as well as their relationship with serum lipid profiles. Objective This study analyzed the association of serum adropin, leptin, LBP levels and lipid profiles in obese children ranging from 5 to 14 years old. Methods Plasma lipid measurements included total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) by standard methods, and serum adropin, leptin and LBP levels was measured by enzyme-linked immunosorbent assay (ELISA). Results One hundred and twenty-four children (9.25 ± 1.59 years) with obesity and 42 controls (8.81 ± 1.94 years) were assessed. Compared with the control group, the serum adropin concentrations in the obesity group were significantly lower, whereas the serum leptin and LBP levels were significantly higher. Pearson's correlation analysis showed that serum adropin levels negatively correlated with TG, waist to hip ratio (WHR) and body mass index (BMI), and positively correlated with HDL-c. Serum LBP levels positively correlated with LDL-c and WHR. After adjusting for LBP, the correlation coefficients of adropin with TG, HDL-c and leptin were more robust. Also, after adjusting for serum LBP, the correlation coefficient of leptin with TG was attenuated, yet remained statistically significant, and the correlation coefficient of leptin with HDL-c was enhanced. Conclusions Children with obesity have decreased serum adropin levels and elevated leptin and LBP levels. Each of the three serum cytokines were associated with lipid metabolism, and this association warrants further study.


Assuntos
Biomarcadores/sangue , Proteínas de Transporte/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Lipídeos/sangue , Glicoproteínas de Membrana/sangue , Obesidade Pediátrica/sangue , Obesidade Pediátrica/epidemiologia , Proteínas de Fase Aguda , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , China/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Resistência à Insulina , Masculino , Prognóstico
11.
J Vasc Surg ; 71(6): 1921-1929, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31784280

RESUMO

OBJECTIVE: Identifying biomarkers for abdominal aortic aneurysms (AAA) could prove beneficial in prognosis of AAA and thus the selection for treatment. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein that is highly expressed in aorta. MFAP4 is involved in several tissue remodeling-related diseases. We aimed to investigate the potential role of plasma MFAP4 (pMFAP4) as a biomarker of AAA. METHODS: Plasma samples and data were obtained for 504 male AAA patients and 188 controls in the Viborg Vascular (VIVA) screening trial. The pMFAP4 levels were measured by Alphalisa. The Mann-Whitney U test assessed differences in pMFAP4 levels between the presence and absence of different exposures of interest. The correlation between pMFAP4 and aorta growth rate were investigated through spearman's correlation analysis. Immunohistochemistry and multiple logistic regression adjusted for potential confounders assessed the association between pMFAP4 and AAA. Multiple linear regression assessed the correlation between pMFAP4 and aorta growth rate. Cox regression and competing risk regression were used to investigate the correlation between AAA patients with upper tertile pMFAP4 and the risk of undergoing later surgical repair. RESULTS: A significant negative correlation between pMFAP4 and aorta growth rate was observed using spearman's correlation analysis (ρ = -0.14; P = .0074). However, this finding did not reach significance when applying multiple linear regression. A tendency of decreased pMFAP4 was observed in AAA using immunohistochemistry. Competing risk regression adjusted for potential confounders indicated that patients with upper tertile pMFAP4 had a hazard ratio of 0.51 (P = .001) for risk of undergoing later surgical repair. CONCLUSIONS: High levels of pMFAP4 are associated with a decreased likelihood of receiving surgical repair in AAA. This observation warrants confirmation in an independent cohort.


Assuntos
Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/cirurgia , Proteínas de Transporte/sangue , Proteínas da Matriz Extracelular/sangue , Glicoproteínas/sangue , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Biomarcadores/sangue , Dinamarca , Progressão da Doença , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Regulação para Cima
12.
Clin Exp Rheumatol ; 38(1): 122-128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31498068

RESUMO

OBJECTIVES: To study circulating MFAP4 in rheumatoid arthritis (RA) and its associations with clinical phenotype. METHODS: Early RA (ERA): 47 patients with newly diagnosed, treatment naïve RA were included. Serum MFAP4, clinical and laboratory disease variables were recorded serially during 12 months of intensive synovitis suppressive treatment. Long-standing RA (LRA): 317 patients participated, all receiving DMARD treatment. Disease activity, autoantibody status, extra-articular manifestations and cardiovascular morbidity were recorded. Paired serum and synovial fluid samples were obtained from 13 untreated ERA patients. Healthy blood donors served as reference points. MFAP4 was quantified by AlphaLISA immunoassay. Univariate, multivariate and mixed effects regression models were applied in the statistical analysis. RESULTS: ERA: MFAP4 increased from baseline and was significantly elevated at the 12-month follow-up, 17.8 U/l [12.6;24.1] vs. healthy controls, 12.7 U/l [9.5;15.6], p<0.001. MFAP4 did not correlate with joint counts or C-reactive protein. LRA: MFAP4 was increased, 25.9 U/l [20.4;33.7] vs. healthy controls, 17.6 U/l [13.7;21.2], p<0.0001, but did not correlate with disease activity measures or presence of extra-articular manifestations. Notably, MFAP4 correlated inversely with smoking (p<0.0001) and presence of antibodies against cyclic citrullinated peptides (anti-CCP), p=0.005. There was a positive association with systolic blood pressure, p=0.001 and co-occurrence of three cardiovascular events and/or risk factors, p<0.0001. The serum:synovial fluid MFAP4 ratio was 2:1. CONCLUSIONS: MFAP4 increases from diagnostic baseline despite intensive treatment but does not associate with synovitis at early or late stages of RA. Correlation patterns indicate that increased MFAP4 may reflect enhanced RA-related vascular remodelling.


Assuntos
Artrite Reumatoide/sangue , Proteínas de Transporte/sangue , Proteínas da Matriz Extracelular/sangue , Glicoproteínas/sangue , Sinovite/sangue , Artrite Reumatoide/patologia , Autoanticorpos , Comorbidade , Humanos , Peptídeos Cíclicos/imunologia , Líquido Sinovial , Sinovite/patologia
13.
J Microbiol Immunol Infect ; 53(1): 157-162, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31029530

RESUMO

BACKGROUND: Human leptospirosis, or commonly known as "rat urine disease" is a zoonotic disease that is caused by the bacteria called Leptospira sp. The incidence rate of leptospirosis has been under-reported due to its unspecific clinical symptoms and the limitations of current laboratory diagnostic methods. Leptospirosis can be effectively treated with antibiotics in the early stage, and it is a curable disease but the accuracy to diagnose the infection is rarely achieved. METHODS: The present pilot study investigated plasma protein profiles of leptospirosis patients and compared them against two control groups which consisted of dengue patients and healthy individuals. The plasma protein digests were analyzed using shotgun approach by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Protein abundances were estimated from the exponentially modified protein abundance index (emPAI) values. Plasma proteins in leptospirosis patients with at least two-fold differential expression compared to dengue and healthy control groups (p < 0.05, ANOVA) were identified. RESULTS: Lipopolysaccharide (LPS)-binding protein (LBP) was found to be the only protein that has significant different expression between leptospirosis and the two control groups. The expression levels of leucine-rich alpha-2-glycoprotein (LRG1) and alpha-1-antichymotrypsin (ACT) were different significantly between leptospirosis and healthy group but not to the dengue control group. CONCLUSION: This is the first plasma proteome-based study on leptospirosis that reports the differential expression of LBP compared to both dengue and healthy controls, which has not been previously reported in the context of leptospirosis.


Assuntos
Proteínas de Fase Aguda/genética , Proteínas de Transporte/sangue , Proteínas de Transporte/genética , Leptospirose/sangue , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/genética , Proteoma/análise , Adolescente , Adulto , Cromatografia Líquida , Dengue/sangue , Humanos , Projetos Piloto , Proteômica , Espectrometria de Massas em Tandem , Adulto Jovem
14.
Infection ; 48(2): 241-248, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31873850

RESUMO

PURPOSE: Differential diagnosis between acute viral and bacterial infection is an emerging common challenge for a physician in the emergency department. Serum C-reactive protein (CRP) is used to support diagnosis of bacterial infection, but in patients admitted with low CRP, its ability to discriminate between viral and bacterial infections is limited. We aimed to use two consecutive CRP measurements in order to improve differential diagnosis between bacterial and viral infection. METHODS: A single-center retrospective cohort (n = 1629) study of adult patients admitted to the emergency department with a subsequent microbiological confirmation of either viral or bacterial infection. Trend of CRP was defined as the absolute difference between the first two measurements of CRP divided by the time between them, and we investigated the ability of this parameter to differentiate between viral and bacterial infection. RESULTS: In patients with relatively low initial CRP concentration (< 60 mg/L, n = 634 patients), where the uncertainty regarding the type of infection is the highest, the trend improved diagnosis accuracy (AUC 0.83 compared to 0.57 for the first CRP measurement). Trend values above 3.47 mg/L/h discriminated bacterial from viral infection with 93.8% specificity and 50% sensitivity. CONCLUSIONS: The proposed approach for using the kinetics of CRP in patients whose first CRP measurement is low can assist in differential diagnosis between acute bacterial and viral infection.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Infecções Bacterianas/diagnóstico , Proteínas de Transporte/metabolismo , Proteínas com Domínio LIM/metabolismo , Viroses/diagnóstico , Doença Aguda , Proteínas Adaptadoras de Transdução de Sinal/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Infecções Bacterianas/sangue , Proteínas de Transporte/sangue , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Proteínas com Domínio LIM/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Viroses/sangue
15.
BMC Gastroenterol ; 19(1): 223, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864303

RESUMO

BACKGROUND: Malnutrition is a common problem among children with chronic liver diseases (CLD). We aimed to assess the nutritional status of children with CLD and to correlate the anthropometric indices with the severity of liver disease, liver function tests, insulin growth factor-1 (IGF-1) and 25-hydroxy vitamin D (25- OH D). METHODS: A total of 69 patients with CLD and 50 healthy controls (6 months - 6 years) were included in the study. Nutritional status was assessed by anthropometric indices expressed in standard deviation score (Z score), biochemical, hematological and clinical parameters. RESULTS: We found 52.2% of CLD patients underweight by weight for age (W/A); 50.2% were stunted by height for age/ length for age (HAZ or LAZ); and 39% exhibited wasting by weight/height or (length) for age (W/HZ or W/LZ) z scores analysis. The mean values of z scores for all anthropometric parameters were significantly correlated with unconjugated and conjugated bilirubin and INR (p < 0.05), except HAZ or LAZ. Also, a significant correlation to albumin was found, except for W/HZ or (W/LZ) (p = 0.157). The z scores < - 2 SD based on W/ H versus arm indicators showed significant differences in MUAC, UAA and AMA (p < 0.001). We found no correlation between anthropometric z-scores and the mean IGF-1 and (25- OH D) values (p > 0.05). Malnutrition was directly correlated with the severity of hepatic dysfunction, particularly, Child-Pugh C cases. The mean IGF-1 and (25- OH D) values were significantly correlated with the severity of liver disease (p < 0.001). CONCLUSIONS: Our results identified anthropometric arm indicators and MUAC/A measurements as an effective applied methods for assessing nutritional status in CLD children. Moreover, Integrating comprehensive clinical assessment, anthropometric measurements and objective biochemical analyses is essential for evaluation, follow-up and management of CLD children with variable degree of malnutrition.


Assuntos
Hepatopatias/complicações , Desnutrição/diagnóstico , Avaliação Nutricional , Fatores Etários , Braço/anatomia & histologia , Estatura , Peso Corporal , Proteínas de Transporte/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Doença Crônica , Estudos Transversais , Egito , Feminino , Transtornos do Crescimento/sangue , Transtornos do Crescimento/diagnóstico , Cabeça/anatomia & histologia , Humanos , Lactente , Fator de Crescimento Insulin-Like I/análise , Hepatopatias/sangue , Testes de Função Hepática , Masculino , Desnutrição/sangue , Desnutrição/etiologia , Albumina Sérica/análise , Índice de Gravidade de Doença , Pregas Cutâneas , Magreza/sangue , Magreza/diagnóstico , Vitamina D/análogos & derivados , Vitamina D/sangue , Síndrome de Emaciação/sangue , Síndrome de Emaciação/diagnóstico
16.
Int J Chron Obstruct Pulmon Dis ; 14: 2433-2440, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802861

RESUMO

Background: Chronic obstructive pulmonary disease (COPD) has been introduced as a major public health problem. It has been suggested that disruption in function or some adipokines and serum proteins' signaling could play crucial roles in lung diseases. This study's purpose was to investigate the association between serum levels of S100A1, ZAG, and adiponectin with FEV1 in COPD patients. Methods: In this cross-sectional study, 90 clinically stable outpatient males with age ranging from 40 to 70 years with COPD diagnosis - FEV1/FVC < 70% - were divided into two groups: mild-moderate COPD patients; FEV1 ≥ 50 (n=52) VS severe and very severe COPD patients; FEV1 < 50 (n=38). The serum levels of ZAG, S100A1, and adiponectin were measured by the use of enzyme-linked immunosorbent assay. Results: In the present study, lower FEV1 was significantly associated with increased risk of cachexia (OR = 5.76, 95% CI: 2.28-14.54). The serum level of ZAG was significantly higher in the mild-moderate COPD patients in comparison with the severe-very severe COPD patients (p<0.035). However, the resting metabolic rate (RMR) level was significantly higher in FEV1<50 group compared to FEV1≥50 group (p<0.024). Also, strong positive associations between serum S100A1-ZAG, serum adiponectin-ZAG, and serum adiponectin-S100A1 (ß>0.800, p<0.001) were shown. Conclusion: In the present study, we found that low FEV1 was associated with increased risk of cachexia in COPD patients. Additionally, lower serum level of ZAG and higher RMR were observed in patients with severe-very severe COPD as compared to mild-moderate COPD. Therefore, it could be claimed that there is a mechanistic chain of causality between FEV1, serum ZAG, RMR, and cachexia.


Assuntos
Caquexia/etiologia , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Adipocinas , Adiponectina/sangue , Adulto , Idoso , Biomarcadores/sangue , Composição Corporal , Caquexia/diagnóstico , Caquexia/fisiopatologia , Proteínas de Transporte/sangue , Estudos Transversais , Feminino , Volume Expiratório Forçado , Glicoproteínas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Risco , Proteínas S100/sangue , Capacidade Vital
17.
Biomed Res Int ; 2019: 6128410, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781629

RESUMO

Introduction: The increasing knowledge of adropin, afamin, and neudesin and the regulation of glucose metabolism and insulin resistance allows for the assessment of the differences in their concentrations between the groups with varied duration of diabetes mellitus (DM). Aim of the Study: Assessment of serum levels of adropin, afamin, and neudesin in children with type 1 diabetes, with respect to the disease duration. Materials and Methods: The study consisted of 138 patients aged 5-18 years (M 40.58%). Children with type 1 diabetes (n = 68) were compared to the control group (n = 70). The diabetic group was divided into 4 subgroups: (I) newly diagnosed patients, after an episode of ketoacidosis (n = 14), (II) duration no longer than 5 years (n = 18), (III) 5 to 10 years (n = 27), and (IV) longer than 10 years (n = 9). Serum concentrations of adropin, afamin, and neudesin were assessed and compared between the groups of patients. The criterion for statistical significance was p < 0.05. Results: The concentrations of adropin and afamin across all subgroups were lower than that in the control group, while neudesin levels were higher in diabetic patients compared to the control group. The differences were statistically significant. Conclusions: Adropin, afamin, and neudesin may play a major role in the regulation of glucose metabolism and have a significant potential as novel biomarkers to predict future metabolic disorders. However, further multicentre studies on a larger cohort of patients are necessary to specify the role of these substances in the course and treatment of type 1 diabetes.


Assuntos
Biomarcadores/sangue , Proteínas de Transporte/sangue , Diabetes Mellitus Tipo 1/sangue , Glicoproteínas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Proteínas do Tecido Nervoso/sangue , Adolescente , Proteínas Sanguíneas/análise , Criança , Pré-Escolar , Feminino , Glucose/metabolismo , Hemoglobina A Glicada , Humanos , Cetose , Masculino , Doenças Metabólicas/sangue , Albumina Sérica Humana , Adulto Jovem
18.
Hum Mol Genet ; 28(24): 4208-4218, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31691802

RESUMO

While much work has been done in associating differentially methylated positions (DMPs) to type 2 diabetes (T2D) across different populations, not much attention has been placed on identifying its possible functional consequences. We explored methylation changes in the peripheral blood of Filipinos with T2D and identified 177 associated DMPs. Most of these DMPs were associated with genes involved in metabolism, inflammation and the cell cycle. Three of these DMPs map to the TXNIP gene body, replicating previous findings from epigenome-wide association studies (EWAS) of T2D. The TXNIP downmethylation coincided with increased transcription at the 3' UTR, H3K36me3 histone markings and Sp1 binding, suggesting spurious transcription initiation at the TXNIP 3' UTR as a functional consequence of T2D methylation changes. We also explored potential epigenetic determinants to increased incidence of T2D in Filipino immigrants in the USA and found three DMPs associated with the interaction of T2D and immigration. Two of these DMPs were located near MAP2K7 and PRMT1, which may point towards dysregulated stress response and inflammation as a contributing factor to T2D among Filipino immigrants.


Assuntos
Proteínas de Transporte/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Adulto , Americanos Asiáticos , Proteínas de Transporte/sangue , Proteínas de Transporte/metabolismo , Metilação de DNA , Diabetes Mellitus Tipo 2/metabolismo , Epigênese Genética , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Pessoa de Meia-Idade
19.
Ann Endocrinol (Paris) ; 80(5-6): 280-285, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31590893

RESUMO

Resistance to thyroid hormones syndrome is defined as increased thyroxine (T4) and triiodothyronine (T3) concentrations associated with normal or sometimes increased thyrotropin (TSH) concentration. This is usually due to a pathogenic variant with loss of function of the gene coding for thyroid hormone receptor ß (THRB). This discrepancy in thyroid hormones (TH) and TSH concentrations is also frequently observed in the presence of analytical interference, notably alteration of TH transport proteins in serum. During 2017, 58 samples were sent to our laboratory in the Angers University Hospital Rare Thyroid and Hormone Receptor Disease Reference Center in order to identify an etiology for discrepant TSH and TH results. We sequenced the genes involved in TH regulation, action and transport (THRB,THRA, SECISBP2, SLC16A, ALB, TTR, SERPINA7). Free T4 and free T3 assay were performed with a second immunoassay (Siemens ADVIA Centaur). A genetic cause of discrepancy in TH and TSH concentrations, with mutation in THRB, was found in 26% of cases (15/58). Biological interference due to TH serum transport protein variant was found in 24% (14/58) of cases. No pathogenic variants were found in the other genes studied. Biological interference was also suspected in 26% of cases without genetic variant, in which the biological discrepancy was not confirmed by a second analytical technique (15/58). Finally, no etiology for the biological discrepancy could be found in 24% of cases (14/58). Clinically, patients in whom biological discrepancy was due to analytic interference were more often asymptomatic, and patients with no identified etiology tended to be older. To limit diagnostic errors associated with the finding of discrepant TSH and TH, we recommend initially conducting a second thyroid function test (TSH, free T4 and free T3) with a different assay, and then screening for a genetic variant in gene coding for thyroid hormone receptor ß (THRB) and the TH serum transport proteins (ALB, TTR, SERPINA7).


Assuntos
Erros de Diagnóstico/estatística & dados numéricos , Mutação/genética , Testes de Função Tireóidea/métodos , Receptores beta dos Hormônios Tireóideos/genética , Síndrome da Resistência aos Hormônios Tireóideos/diagnóstico , Síndrome da Resistência aos Hormônios Tireóideos/genética , Adolescente , Adulto , Idoso , Proteínas de Transporte/sangue , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Síndrome da Resistência aos Hormônios Tireóideos/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
20.
Artigo em Inglês | MEDLINE | ID: mdl-31656691

RESUMO

Background: Paraneoplastic chorea is typically a subacute progressive hyperkinetic movement disorder. The mainstay of treatment is managing the underlying neoplasm. However, the clinical course may be variable, and effective symptomatic management can precede the start of cancer treatment. Case report: A 63-year-old man presented with insidious onset, slowly progressive generalized chorea for 1 year, later diagnosed as anti-CV2/CRMP5 autoantibody positive paraneoplastic chorea. His chorea was markedly improved with intravenous amantadine. Discussion: In patients with anti-CV2/CRMP5 autoantibody-related chorea, sequential follow-up of brain magnetic resonance imaging reveals progression from active inflammation to atrophy. Our report highlights the efficacy of intravenous amantadine in paraneoplastic chorea.


Assuntos
Amantadina/administração & dosagem , Autoanticorpos/sangue , Proteínas de Transporte/sangue , Coreia/sangue , Coreia/tratamento farmacológico , Hidrolases/sangue , Proteínas Associadas aos Microtúbulos/sangue , Administração Intravenosa , Coreia/diagnóstico por imagem , Dopaminérgicos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
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