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1.
Food Res Int ; 173(Pt 2): 113413, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37803748

RESUMO

According to previous research, adding CaCl2 to the salting solution improves the quality of salted separated egg yolk. To further understand the improvement mechanism of CaCl2, this paper investigated the effect of CaCl2 on the structure of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) during the salting process. The results indicated that the addition of CaCl2 can affect the composition of HDL and LDL apolipoproteins, improving the orderliness of the HDL structure and the looseness of the LDL structure. It was discovered by atomic force microscopy (AFM) that adding CaCl2 to the salting solution can weaken the aggregation behavior of HDL. Simultaneously, the addition of CaCl2 decreased the relative content of intermolecular ß-sheets in the secondary structure of HDL and LDL, influenced their tertiary conformation, and prevented HDL and LDL from participating in the formation of a three-dimensional gel structure by influencing their hydrogen bonds and hydrophobic interactions.


Assuntos
Lipoproteínas HDL , Lipoproteínas LDL , Lipoproteínas HDL/análise , Lipoproteínas HDL/química , Lipoproteínas LDL/química , Gema de Ovo/química , Cloreto de Cálcio/farmacologia
2.
Sci Total Environ ; 855: 158596, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36089046

RESUMO

BACKGROUND: Evidence concerning the influence of air pollution on metabolic syndrome (MetS) is still limited. We aimed to investigate whether sustained exposure to air pollutants are associated with increased prevalence of MetS and its individual components. METHODS: We conducted a cross-sectional study comprised of 14,097 individuals participated in the first or third survey of the CHARLS. The personal cumulative (3-year averaged) exposure concentrations of nitrogen dioxide (NO2), particulate matter (PM) with a diameter of 1.0 µm or less (PM1), PM with a diameter of 10 µm or less (PM10) and PM with a diameter of 2.5 µm or less (PM2.5) were estimated using a spatiotemporal random forest model at 0.1° × 0.1° spatial resolution based on residential address of each participant provided. We utilized logistic regression models to estimate the associations of the four air pollutants with the prevalence of MetS and its individual components, and performed interaction analyses to evaluate potential effect modifications by gender, health status, age and drinking status. RESULTS: Sustained exposure to air pollutants is associated with increased prevalence of MetS. For every 10 µg/m3 increase in NO2, PM1, PM10 and PM2.5, the adjusted odds ratio (OR) of MetS was 2.276 (95 % CI: 2.148, 2.412), 1.207 (95 % CI: 1.155, 1.263), 1.027 (95 % CI: 1.006, 1.048) and 1.027 (95 % CI: 0.989, 1.066), respectively. For MetS components, we observed significant associations between NO2, PM1, PM10 and central obesity, high blood pressure, elevated fasting glucose and low high-density lipoprotein cholesterol. For example, the adjusted OR of low high-density lipoprotein cholesterol for every 10 µg/m3 increase in NO2 was 1.855 (95 % CI: 1.764, 1.952). We also identified that age could significantly modified the association between NO2 and prevalence of MetS. CONCLUSIONS: Chinese adults sustained exposure to higher concentrations of air pollutants are associated with increased prevalence of MetS and its components.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Síndrome Metabólica , Humanos , Adulto , Dióxido de Nitrogênio/análise , Síndrome Metabólica/epidemiologia , Prevalência , Estudos Transversais , Exposição Ambiental/análise , Poluição do Ar/análise , Material Particulado/análise , Poluentes Atmosféricos/análise , China/epidemiologia , Lipoproteínas HDL/análise , Colesterol
3.
Postgrad Med ; 133(7): 822-829, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34281466

RESUMO

BACKGROUND: Recent studies have identified monocyte to high-density lipoprotein ratio (MHR) as a simple, practical surrogate of atherosclerosis. Considering atherosclerosis is a major mechanism of coronary heart disease (CHD). The present study aims to evaluate the association between MHR and the prevalence of CHD. METHODS AND RESULTS: The present cross-sectional work included 6442 participants (mean age: 59.57 years, 60.2% females), all of them were included from rural areas of northern China between October 2019 to April 2020. MHR was acquired as monocytes count divided by high-density lipoprotein concentration. Prevalent CHD researched 3.14%. After adjustment of sex, age, current drinking and smoking, BMI, WC, diabetes, hypertension, LDL-C, TG, eGFR, lipid-lowering therapy and cerebrovascular disease history, each standard deviation increase of MHR cast a 39.5% additional CHD risk. Furthermore, the top quartile of MHR had an additional 89.0% CHD risk than the bottom quartile. Besides, smooth curve fitting revealed a linear pattern of the association. Additionally, the stratified evaluation showed a robust correlation among the subgroups divided by CHD risk factors. Finally, area under the curve demonstrated an advancement when including MHR into common CHD risk factors (0.744 vs 0.761, p < 0.001). Consistently, reclassification analysis indicated the improvement from MHR (all P = 0.003). CONCLUSION: Our work suggests the robust and linear relationship between MHR and the prevalent CHD in a general population, providing epidemiological evidence for laboratory studies. More importantly, the findings implicate the efficacy of MHR to be a potential indicator to identify the prevalent CHD.


Assuntos
Doença das Coronárias/sangue , Lipoproteínas HDL/análise , Monócitos/citologia , Idoso , Aterosclerose/sangue , China , Comorbidade , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade
4.
J Pediatr ; 235: 130-137, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33812920

RESUMO

OBJECTIVE: To assess prevalence of and factors associated with left ventricular diastolic dysfunction (LVDD) in youth with obesity and elevated blood pressure (BP). STUDY DESIGN: This was a cross-sectional analysis of baseline and follow-up visits of 83 youth, 5-21 years, evaluated for overweight/obesity and elevated BP in a multidisciplinary clinic. LVDD was defined according to established adult criteria (LVDDadult; E/A < 1, E/e' > 14, or e'/a' < 0.8) and pediatric criteria (LVDDpeds; E/A <10th percentile, E/e' >99th percentile, or e'/a' <1st percentile) based on data from 103 age-sex matched healthy controls. Baseline factors associated with LVDDpeds were examined using Wilcoxon rank sum and χ2 tests. Multiple logistic regression analyses using generalized estimating equations to account for repeated measures evaluated the associations of adiposity and BP with LVDDpeds. RESULTS: The prevalence of LVDD ranged from 1.2% to 2.7% when we used adult criteria and 19% to 28% when we used pediatric criteria. Those with LVDDpeds were older, predominantly male, and non-African American and had greater weight, BP, BP medication use, and non-high-density lipoprotein cholesterol than those without LVDDpeds. Diastolic BP z score was associated with LVDDpeds by E/A (OR 1.95, 95% CI 1.15-3.32, P = .014) after we adjusted for age, sex, race, BP medications, and body mass index z score. CONCLUSIONS: LVDD was present in a substantial proportion of youth with overweight/obesity and elevated BP using pediatric criteria. Those with LVDDpeds had significantly greater measures of adiposity and BP compared with those without LVDDpeds, and diastolic BP z score was an independent predictor of LVDDpeds by E/A. These data emphasize the importance of prevention and treatment of cardiovascular disease risk factors in childhood.


Assuntos
Diástole , Hipertensão/epidemiologia , Obesidade Pediátrica/epidemiologia , Disfunção Ventricular Esquerda/epidemiologia , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , Lipoproteínas HDL/análise , Masculino , Distribuição por Sexo , Adulto Jovem
5.
Biomed Res Int ; 2021: 9241259, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33575357

RESUMO

High-density lipoprotein- (HDL-) cholesterol measurements are generally used in the diagnosis of cardiovascular diseases. However, HDL is a complicated heterogeneous lipoprotein, and furthermore, it can be converted into dysfunctional forms during pathological conditions including inflammation. Therefore, qualitative analysis of pathophysiologically diversified HDL forms is important. A recent study demonstrated that serum amyloid A (SAA) can remodel HDL and induce atherosclerosis not only over long periods of time, such as during chronic inflammation, but also over shorter periods. However, few studies have investigated rapid HDL remodeling. In this study, we analyzed HDL samples from patients undergoing orthopedic surgery inducing acute inflammation. We enrolled 13 otherwise healthy patients who underwent orthopedic surgery. Plasma samples were obtained on preoperative day and postoperative days (POD) 1-7. SAA, apolipoprotein A-I (apoA-I), and apolipoprotein A-II (apoA-II) levels in the isolated HDL were determined. HDL particle size, surface charge, and SAA and apoA-I distributions were also analyzed. In every patient, plasma SAA levels peaked on POD3. Consistently, the HDL apoA-I : apoA-II ratio markedly decreased at this timepoint. Native-polyacrylamide gel electrophoresis and high-performance liquid chromatography revealed the loss of small HDL particles during acute inflammation. Furthermore, HDL had a decreased negative surface charge on POD3 compared to the other timepoints. All changes observed were SAA-dependent. SAA-dependent rapid changes in HDL size and surface charge were observed after orthopedic surgery. These changes might affect the atheroprotective functions of HDL, and its analysis can be available for the qualitative HDL assessment.


Assuntos
Inflamação/sangue , Lipoproteínas HDL/análise , Lipoproteínas HDL/química , Procedimentos Ortopédicos/efeitos adversos , Complicações Pós-Operatórias/sangue , Proteína Amiloide A Sérica/análise , Cromatografia Líquida de Alta Pressão , Humanos , Inflamação/etiologia , Tamanho da Partícula
6.
Asian J Androl ; 23(4): 400-408, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33586698

RESUMO

Although localized prostate cancer (PCa) can be cured by prostatectomy and radiotherapy, the development of effective therapeutic approaches for advanced prostate cancer, including castration-resistant PCa (CRPC) and neuroendocrine PCa (NEPC), is lagging far behind. Identifying a novel prognostic and diagnostic biomarker for early diagnosis and intervention is an urgent clinical need. Here, we report that apolipoprotein A-I (ApoA-I), the major component of high-density lipoprotein (HDL), is upregulated in PCa based on both bioinformatics and experimental evidence. The fact that advanced PCa shows strong ApoA-I expression reflects its potential role in driving therapeutic resistance and disease progression by reprogramming the lipid metabolic network of tumor cells. Molecularly, ApoA-I is regulated by MYC, a frequently amplified oncogene in late-stage PCa. Altogether, our findings have revealed a novel indicator to predict prognosis and recurrence, which would benefit patients who are prone to progress to metastasis or even NEPC, which is the lethal subtype of PCa.


Assuntos
Apolipoproteína A-I/metabolismo , Neoplasias da Próstata/metabolismo , Análise de Variância , Linhagem Celular/metabolismo , Linhagem Celular/fisiologia , Progressão da Doença , Humanos , Lipoproteínas HDL/análise , Lipoproteínas HDL/farmacologia , Masculino , Prognóstico , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia
7.
J Atheroscler Thromb ; 28(7): 730-741, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32999208

RESUMO

AIM: Recently, it has been established that most of the pleiotropic effects of high-density lipoprotein (HDL) are attributed to sphingosine 1-phosphate (S1P), which rides on HDL via apolipoprotein M (ApoM). In subjects with diabetes mellitus, both the pleiotropic effects of HDL and its role in reverse cholesterol transport are reported to be impaired. To elucidate the mechanisms underlying the impaired pleiotropic effects of HDL in subjects with diabetes, from the aspects of S1P and ApoM. METHODS: The incubation of HDL in a high-glucose condition resulted in the dimerization of ApoM. Moreover, the treatment of HDL with methylglyoxal resulted in the modulation of the ApoM structure, as suggested by the results of western blot analysis, isoelectric focusing electrophoresis, and two-dimensional gel electrophoresis, which was reversed by treatment with anti-glycation reagents. RESULTS: The glycation of HDL resulted in impaired binding of the glycated HDL to S1P, and the S1P on glycated HDL degraded faster. In the case of human subjects, on the other hand, although both the serum ApoM levels and the ApoM content in HDL were lower in subjects with diabetes, we did not observe the polymerization of ApoM. CONCLUSIONS: Modulation of the quantity and quality of ApoM might explain, at least in part, the impaired functions of HDL in subjects with diabetes mellitus. ApoM might be a useful target for laboratory testing and/or the treatment of diabetes mellitus.


Assuntos
Apolipoproteínas M/metabolismo , Diabetes Mellitus , Lipoproteínas HDL/metabolismo , Lisofosfolipídeos/metabolismo , Esfingosina/análogos & derivados , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/fisiologia , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Descoberta de Drogas , Eletroforese em Gel Bidimensional/métodos , Humanos , Focalização Isoelétrica/métodos , Lipoproteínas HDL/análise , Esfingosina/metabolismo
8.
J Atheroscler Thromb ; 28(7): 703-715, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33028763

RESUMO

AIMS: HDL particles have various anti-atherogenic functions, whereas HDL from atherosclerotic patients was demonstrated to be dysfunctional. One possible mechanism for the formation of dysfunctional HDL is the oxidation of its components. However, oxidized HDLs (Ox-HDLs) remain to be well investigated due to lack of reliable assay systems. METHODS: We have developed a novel sandwich enzyme-linked immunosorbent assay (ELISA) for Ox-HDL by using the FOH1a/DLH3 antibody, which can specifically recognize oxidized phosphatidylcholine, a major component of HDL phospholipid (HDL-PL). We defined forced oxidation of 1 mg/L HDL-PL as 1 U/L Ox-HDL. We assessed serum Ox-HDL levels of normolipidemic healthy subjects ( n=94) and dyslipidemic patients (n=177). RESULTS: The coefficients of variation of within-run and between-run assays were 12.5% and 13.5%. In healthy subjects, serum Ox-HDL levels were 28.5±5.0 (mean±SD) U/L. As Ox-HDL levels were moderately correlated with HDL-PL (r=0.59), we also evaluated the Ox-HDL/HDL-PL ratio, which represents the proportion of oxidized phospholipids in HDL particles. In dyslipidemic patients, Ox-HDL levels were highly variable and ranged from 7.2 to 62.1U/L, and were extremely high (50.4±13.3U/L) especially in patients with hyperalphalipoproteinemia due to cholesteryl ester transfer protein deficiency. Regarding patients with familial hypercholesterolemia, those treated with probucol, which is a potent anti-oxidative and anti-hyperlipidemic drug, showed significantly lower Ox-HDL (16.2±5.8 vs. 30.2±5.4, p<0.001) and Ox-HDL/HDL-PL ratios (0.200±0.035 vs. 0.229±0.031, p=0.015) than those without probucol. CONCLUSION: We have established a novel sandwich ELISA for Ox-HDL, which might be a useful and easy strategy to evaluate HDL functionality, although the comparison study between this Ox-HDL ELISA and the assay of HDL cholesterol efflux capacity remains to be done. Our results indicated that probucol treatment may be associated with lower Ox-HDL levels.


Assuntos
Aterosclerose/metabolismo , Dislipidemias , Ensaio de Imunoadsorção Enzimática/métodos , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Lipoproteínas HDL , Oxirredução/efeitos dos fármacos , Probucol , Adulto , Antioxidantes/uso terapêutico , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/metabolismo , Hipolipemiantes/farmacocinética , Hipolipemiantes/uso terapêutico , Lipoproteínas HDL/análise , Lipoproteínas HDL/metabolismo , Masculino , Probucol/farmacocinética , Probucol/uso terapêutico , Reprodutibilidade dos Testes
9.
Biochemistry ; 59(15): 1455-1464, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32223124

RESUMO

High-density lipoprotein (HDL) is a naturally occurring composite of lipids and lipid-binding proteins. The cholate dialysis method, first reported by Jonas in 1969, is the most widely used approach for reconstituting discoidal HDL (dHDL) in test tubes with phospholipids and the most dominant protein, apolipoprotein A-1 (apoA-I). Here, we show that a dHDL-relevant complex can also be prepared by gently mixing 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and apoA-I or its mutants in ethanol/H2O solutions containing urea at a concentration of a few molar and then incubating the mixture at the gel-liquid crystalline phase transition temperature in test tubes. Subsequent purification steps involve quick dialysis following size exclusion chromatography. The yields (73 ± 3% and 70 ± 1% protein and DMPC, respectively) of the resulting HDL-like nanoparticles, designated as uHDL, were comparable to the values of 68 ± 9% and 71 ± 12% obtained in the cholate dialysis method. Using apoA-I and two mutants, the key factor in this method was found to be urea at the folded and unfolded transition midpoint concentration. By using this urea-assisted method in the presence of a hydrophobic drug, all-trans-retinoic acid (ATRA), one-step preparation of ATRA-loaded uHDL was also possible. The loading efficiency was comparable to that in the mixing of ATRA and uHDL or dHDL reconstituted by the cholate dialysis method. Atomic force microscopy analysis revealed that uHDL and ATRA-loaded uHDL were discoidal. Our urea-assisted method is an easy and efficient method for reconstituting dHDL and can be utilized to prepare various drug-dHDL complexes.


Assuntos
Lipoproteínas HDL/análise , Ureia/química , Apolipoproteína A-I/química , Apolipoproteína A-I/genética , Humanos , Interações Hidrofóbicas e Hidrofílicas , Tretinoína/química
10.
Rev. chil. nutr ; 47(2): 181-189, abr. 2020. tab
Artigo em Inglês | LILACS | ID: biblio-1115487

RESUMO

The objective of this study was to assess the influence of weight gain on the lipid profile of 135 adolescents between 10 - 14 years at baseline and 15 - 19 years at follow-up, enrolled in public schools in Recife, Brazil. The results showed that a BMI z-score correlated with triglycerides (TG) and with high density trigliceride lipopoteine ratio (TG/HDL-c) in males. In females, high z-score correlated with total cholesterol (TC) and low density lipoprotein (LDL-c). In males, for each unit increase in z-score, TG increased by 14.7 mg/dL and the TG/HDL-c ratio increased by 0.4. Among females, TC increased by 9.4 mg/dL, LDL-c increased by 11.6 mg/dL, non-HDL cholesterol increased by 11.8 mg/dL, and HDL-c decreased by 2.3 mg/dL. In males, excessive weight gain was associated with an increase in TG and TG/HDL-c; in females, it was associated with a higher increase in TG/HDL-c and non-HDL cholesterol. However, z-score variation can be a good predictor of lipid profile changes, even in those that are within the normal range.


El objetivo de este estudio fue evaluar la influencia del aumento de peso en el perfil lipídico de 135 adolescentes de edades entre 10 y 14 años de edad al inicio del estudio y de 15 a 19 años en el seguimiento. Los adolescentes pertenecían a escuelas públicas de Recife, Brasil. Los resultados mostraron que el alto puntaje z de indice de masa corporase (IMC) correlacionaba con triglicéridos (TG) y con relación de triglicéridos con lipoproteínas de alta densidad (TG/HDL-c) en los hombres. En las mujeres, puntaje z de IMC se correlacionó con CT y lipoproteína de baja densidad (LDL-c). En los hombres, por cada unidad de aumento en el puntaje z, los TG aumentaron en 14,7 mg/dL y la relación TG / HDL-c aumentó en 0,4; en las mujeres, el CT aumentó en 9,4 mg/dL, el LDL-c aumentó en 11,6 mg/dL, el colesterol no HDL aumentó en 11,8 mg / dL y el HDL-c disminuyó en 2,3 mg/dL. En los hombres, el aumento de peso excesivo se asoció con un aumento de TG y TG/HDL-c; en las mujeres, con un aumento mayor en TG/HDL-c y colesterol no HDL. Sin embargo, la variación z-score puede ser un buen predictor de cambios en el perfil lipídico, incluso en aquellos que se encuentran dentro del rango normal.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Aumento de Peso , Lipídeos/análise , Triglicerídeos/análise , Brasil , Doenças Cardiovasculares/etiologia , Índice de Massa Corporal , Colesterol/análise , Seguimentos , Dislipidemias/complicações , Lipoproteínas HDL/análise , Lipoproteínas LDL/análise
11.
J Pharmacol Exp Ther ; 373(1): 113-121, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31941718

RESUMO

Reconstituted high-density lipoprotein (HDL) containing apolipoprotein A-I (Apo A-I) mimics the structure and function of endogenous (human plasma) HDL due to its function and potential therapeutic utility in atherosclerosis, cancer, neurodegenerative diseases, and inflammatory diseases. Recently, a new class of HDL mimetics has emerged, involving peptides with amino acid sequences that simulate the the primary structure of the amphipathic alpha helices within the Apo A-I protein. The findings reported in this communication were obtained using a similar amphiphilic peptide (modified via conjugation of a myristic acid residue at the amino terminal aspartic acid) that self-assembles (by itself) into nanoparticles while retaining the key features of endogenous HDL. The studies presented here involve the macromolecular assembly of the myristic acid conjugated peptide (MYR-5A) into nanomicellar structures and its characterization via steady-state and time-resolved fluorescence spectroscopy. The structural differences between the free peptide (5A) and MYR-5A conjugate were also probed, using tryptophan fluorescence, FÓ§rster resonance energy transfer (FRET), dynamic light scattering, and gel exclusion chromatography. To our knowledge, this is the first report of a lipoprotein assembly generated from a single ingredient and without a separate lipid component. The therapeutic utility of these nanoparticles (due to their capablity to incorporate a wide range of drugs into their core region for targeted delivery) was also investigated by probing the role of the scavenger receptor type B1 in this process. SIGNIFICANCE STATEMENT: Although lipoproteins have been considered as effective drug delivery agents, none of these nanoformulations has entered clinical trials to date. A major challenge to advancing lipoprotein-based formulations to the clinic has been the availability of a cost-effective protein or peptide constituent, needed for the assembly of the drug/lipoprotein nanocomplexes. This report of a robust, spontaneously assembling drug transport system from a single component could provide the template for a superior, targeted drug delivery strategy for therapeutics of cancer and other diseases (Counsell and Pohland, 1982).


Assuntos
Materiais Biomiméticos/química , Portadores de Fármacos/química , Lipoproteínas HDL/química , Nanopartículas/química , Espectrometria de Fluorescência/métodos , Sequência de Aminoácidos , Materiais Biomiméticos/análise , Portadores de Fármacos/análise , Lipoproteínas HDL/análise , Lipoproteínas HDL/genética , Nanopartículas/análise
12.
J Immunol Methods ; 474: 112637, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31386835

RESUMO

High density lipoproteins (HDL) are considered cardio protective. Apolipoprotein A-I (apoA-I), a major component of HDL helps in reverse cholesterol transport, whose function is greatly affected during atherosclerosis due to oxidation by myeloperoxidase. Amino acid tyrosine residue of apoA-I at position 192 and 166 are sensitive to oxidation by myeloperoxidase resulting in the generation of chlorinated and nitrated apoA-I and they are believed to be present in atherosclerotic plaques and in circulation. These oxidized apoA-I have been suggested as potential indicator(s) of CVD risks in humans. To detect the levels of oxidized apoA-I there is a need for developing monoclonal antibodies (mAbs) with high specificity and sensitivity that could be utilized routinely in clinical immune based assays for blood plasma or for in vivo imaging. In this study, chemically chlorinated apoA-I (chlorinated 192tyrosine- apoA-I) and a short synthetic peptide, containing the corresponding chlorinated tyrosine residue, conjugated to keyhole limpet hemocyanin (KLH) carrier protein were used for immunization. Stable hybridoma clones F7D5 and G11E3 were found to be highly sensitive and reactive towards chlorinated 192tyrosine- apoA-I. Interestingly, these mAbs also displayed positive reaction with atherosclerotic plaques obtained from mouse and human biopsies. In vitro or in vivo diagnostic tests could be developed either by detecting oxidized apoA-I in human plasma or by directly imaging atheroma plaques as both mAbs were shown to stain human atheroma. The anti-chlorinated 192tyrosine- apoA-I mAbs described in this study may have a high diagnostic potential in predicting CVD risks.


Assuntos
Anticorpos Monoclonais/imunologia , Apolipoproteína A-I/análise , Aterosclerose/diagnóstico , Doença da Artéria Coronariana/diagnóstico , Testes Imunológicos , Lipoproteínas HDL/análise , Animais , Especificidade de Anticorpos , Apolipoproteína A-I/imunologia , Aterosclerose/genética , Aterosclerose/imunologia , Aterosclerose/metabolismo , Biomarcadores/análise , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/metabolismo , Modelos Animais de Doenças , Halogenação , Humanos , Lipoproteínas HDL/imunologia , Camundongos Knockout para ApoE , Oxirredução , Placa Aterosclerótica , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Tirosina
13.
Metabolomics ; 15(8): 114, 2019 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-31422486

RESUMO

INTRODUCTION: HDL is associated with increased longevity and protection from multiple chronic diseases. The major HDL protein ApoA-I has a half-life of about 4 days, however, the effects of diet on the composition of HDL particles at this time scale have not been studied. OBJECTIVES: The objective of this study is to investigate the short term dietary effect on HDL lipidomic composition. METHODS: In this randomized order cross-over study, ten healthy subjects consumed a Mediterranean (Med) and a fast food (FF) diet for 4 days, with a 4-day wash-out between treatments. Lipidomic composition was analyzed in isolated HDL fractions by an untargeted LC-MS method with 15 internal standards. RESULTS: HDL phosphatidylethanolamine (PE) content was increased by FF diet, and 41 out of 170 lipid species were differentially affected by diet. Saturated fatty acids (FAs) and odd chain FA were enriched after FF diet, while very-long chain FA and unsaturated FA were enriched after Med diet. The composition of phosphatidylcholine (PC), triacylglycerol (TG) and cholesteryl ester (CE) were significantly altered to reflect the FA composition of the diet whereas the composition of sphingomyelin (SM) and ceramides were generally unaffected. CONCLUSION: Results from this study indicate that the HDL lipidome is widely remodeled within 4 days of diet change and that certain lipid classes are more sensitive markers of diet whereas other lipid classes are better indicators of non-dietary factors.


Assuntos
Dieta Mediterrânea , Fast Foods , Lipidômica , Lipoproteínas HDL/metabolismo , Adolescente , Adulto , Estudos Cross-Over , Feminino , Voluntários Saudáveis , Humanos , Lipoproteínas HDL/análise , Masculino , Projetos Piloto , Adulto Jovem
14.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(10): 1280-1292, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31185305

RESUMO

Despite strong evidence that high-density lipoproteins (HDLs) modulate the immune response, the role of HDL in allergies is still poorly understood. Many patients with allergic rhinitis (AR) develop a late-phase response, characterized by infiltration of monocytes and eosinophils into the nasal submucosa. Functional impairment of HDL in AR-patients may insufficiently suppress inflammation and cell infiltration, but the effect of AR on the composition and function of HDL is not understood. We used apolipoprotein (apo) B-depleted serum as well as isolated HDL from AR-patients (n = 43) and non-allergic healthy controls (n = 20) for detailed compositional and functional characterization of HDL. Both AR-HDL and apoB-depleted serum of AR-patients showed decreased anti-oxidative capacity and impaired ability to suppress monocyte nuclear factor-κB expression and pro-inflammatory cytokine secretion, such as interleukin (IL)-4, IL-6, IL-8, tumor necrosis factor alpha and IL-1 beta. Sera of AR-patients showed decreased paraoxonase and cholesteryl-ester transfer protein activities, increased lipoprotein-associated phospholipase A2 activity, while lecithin-cholesterol acyltransferase activity and cholesterol efflux capacity were not altered. Surprisingly, apoB-depleted serum and HDL from AR-patients showed an increased ability to suppress eosinophil effector responses upon eotaxin-2/CCL24 stimulation. Mass spectrometry and biochemical analyses showed reduced levels of apoA-I and phosphatidylcholine, but increased levels of apoA-II, triglycerides and lyso-phosphatidylcholine in AR-HDL. The changes in AR-HDL composition were associated with altered functional properties. In conclusion, AR alters HDL composition linked to decreased anti-oxidative and anti-inflammatory properties but improves the ability of HDL to suppress eosinophil effector responses.


Assuntos
Lipoproteínas HDL/imunologia , Rinite Alérgica/imunologia , Adolescente , Adulto , Criança , Citocinas/análise , Citocinas/imunologia , Feminino , Humanos , Imunoglobulina E/imunologia , Lipoproteínas HDL/análise , Masculino , Monócitos/imunologia , Adulto Jovem
15.
BMJ Open ; 9(3): e021153, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30826754

RESUMO

OBJECTIVES: To elucidate the bidirectional temporal relationship between elevated faecal haemoglobin (f-Hb) concentration and metabolic syndrome (MetS). DESIGN: A longitudinal cohort study was conducted by utilising data on community-based periodical screening for colorectal cancer with faecal immunochemical test (FIT) and health check-up for MetS. SETTING: Population-based organised integrated service screening in Keelung city, Taiwan. PARTICIPANTS: We enrolled a total of 62,293 community residents aged 40-79 years. MAIN OUTCOMES AND MEASURES: Bidirectional outcomes of FIT-positive and MetS were measured. RESULTS: The presence of MetS at baseline led to a statistically significant 31% elevated risk of being incident FIT-positive (adjusted HR, (aHR)=1.31, 95% CI: 1.14 to 1.51) whereas the effect of those with FIT-positive at baseline on incident MetS was not statistically significant (aHR=1.06, 95% CI: 0.89 to 1.25) after adjusting for relevant confounders. Such an effect was particularly noted for three individual components (abnormal waist circumference, higher fasting plasma glucose and lower high-density lipoprotein). CONCLUSIONS: Our finding on the presence of MetS before FIT-positive based on bidirectional relationship assessment suggests the control of MetS may contribute to reducing the risk of colorectal neoplasia through the early surveillance of f-Hb. However, such a temporal epidemiological finding still needs to be verified by using other external data.


Assuntos
Neoplasias Colorretais , Fezes/química , Hemoglobinas/análise , Síndrome Metabólica , Adulto , Idoso , Glicemia/análise , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Correlação de Dados , Detecção Precoce de Câncer , Feminino , Humanos , Imunoquímica , Lipoproteínas HDL/análise , Estudos Longitudinais , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Sangue Oculto , Fatores de Risco , Taiwan/epidemiologia , Circunferência da Cintura
16.
Med Sci Monit ; 25: 746-753, 2019 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-30683836

RESUMO

BACKGROUND Idiopathic pulmonary arterial hypertension (IPAH) patients are characterized by elevated triglyceride (TG)-to-HDL cholesterol (HDL-C) ratio, which has been proposed to be an important prognostic factor in this population. The mechanism of this phenomenon remains unknown. We therefore investigated the potential determinants of increased TG/HDL-C ratio in IPAH patients. MATERIAL AND METHODS We prospectively recruited consecutive clinically stable IPAH patients between January 2016 and February 2017. Patients with diabetes or using statins were excluded. Anthropometric measurements included body mass index (BMI) and skinfold thickness; body fat mass was calculated using age and sex-specific equations. We assessed lipid profile, homeostatic model assessment of insulin resistance (HOMA-IR), serum adipokine levels (adiponectin, resistin, leptin, and visfatin), and circulating cytokines (IL-1ß, IL-6, MCP-1, and TNF-α). RESULTS We assessed 47 IPAH patients: 9 of them had been diagnosed with diabetes and 10 were treated with statins; therefore, were excluded them from further analysis. Age, sex distribution, and BMI were similar irrespectively of TG/HDL-C ratio. Patients with increased TG/HDL-C ratio (>3) as compared to patients with TG/HDL-C ≤3 were characterized by higher levels of IL-1ß, MCP-1, and IL-6. TG level was correlated with IL-1ß (R=0.76, p<0.001), IL-6 (R=0.52, p=0.005), TNF-α (R=0.62, p<0.001), and MCP-1 (R=0.63, p<0.001). IL-1ß was also inversely correlated with HDL-C (R=-0.44, p=0.02). We found no differences in concentration of fasting glucose, insulin, HOMA-IR, body fat content, or adipokine levels between patients with higher and lower TG/HDL-C ratios. CONCLUSIONS In IPAH patients, elevated TG/HDL-C ratio is a marker of systemic inflammation.


Assuntos
Hipertensão Pulmonar Primária Familiar/metabolismo , Lipoproteínas HDL/análise , Triglicerídeos/análise , Adipocinas/análise , Adipocinas/sangue , Adulto , Biomarcadores/sangue , Glicemia/análise , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Colesterol/sangue , HDL-Colesterol/sangue , Citocinas/análise , Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Inflamação , Insulina/sangue , Resistência à Insulina , Lipoproteínas HDL/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Triglicerídeos/sangue
17.
Medicine (Baltimore) ; 97(47): e13240, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30461627

RESUMO

There are few existing studies that examine the association between muscle strength and cardiovascular disease (CVD) risk stratified by sex. Evaluation of the handgrip strength is a simple, quick, and inexpensive method to measure muscle strength. This study assessed the association of handgrip strength with the risk of CVD in the Korean general population.Data were derived from a subset of an ongoing nationally representative survey: the Korea National Health and Nutrition Examination Survey (KNHANES), 2014 to 2016, which included 8576 participants aged 40 to 79 years (men: 3807; women: 4769). Individual CVD risk was evaluated by calculating the atherosclerotic cardiovascular disease (ASCVD) risk score and the Framingham risk score (FRS) in subjects aged 40 to 79 years without prior CVD.Multivariate linear regression analysis revealed a significant inverse association (in both men and women) between relative handgrip strength and cardiovascular risk factors, including blood pressure, levels of fasting glucose and triglycerides, waist circumstance, FRS, high sensitivity C-reactive protein levels, and ASCVD risk. A significant positive association between relative handgrip and a low level of high density cholesterol levels in both men and women was identified. In both men and women, subjects in the lowest quartile of handgrip strength had an increased risk of CVD compared with those within the highest quartile (odds ratio range 2.05-3.03).The results of this study suggest that increased handgrip is associated with a lower degree of cardiovascular risk in both men and women. Longitudinal studies are needed to examine the association between muscle strength and cardiovascular risk.


Assuntos
Doenças Cardiovasculares , Força da Mão , Força Muscular , Adulto , Idoso , Glicemia/análise , Proteína C-Reativa/análise , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Correlação de Dados , Feminino , Humanos , Lipoproteínas HDL/análise , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco , Triglicerídeos/análise , Circunferência da Cintura
18.
Medicine (Baltimore) ; 97(26): e11189, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29952970

RESUMO

Acute pancreatitis in pregnancy (APIP) is a rare but dangerous complication. APIP has common symptoms with acute abdomen. Assessment of an acute abdomen is more complicated during pregnancy because the gravid uterus could mask most of symptomatic signs. It has been a challenge to diagnose APIP by physical examination or diagnostic imaging. Case studies on APIP are also limited for analysis on the risk factors associated with the disease. This retrospective study evaluated a series of risk factors from a relatively substantial number of APIP cases to determine early predictors or prognosis markers for APIP.Fifty-nine APIP patients together with 179 random normal pregnant women in Shengjing Affiliated Hospital of China Medical University were included for this retrospective study. Medical parameters of blood test in biochemistry and hematology were compared between 2 groups using t test. Multivariate logistic regression analysis was performed to investigate the relationship between various factors and APIP using Statistical Applied Software (SAS student version).Compared with normal pregnant women, APIP patients have elevated values in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen, creatinine, C-reactive protein, direct bilirubin, fibrin degradation products, gamma-glutamyl transpeptidase (GGT), glucose, lipase, pH and decreased values in albumin, fibrinogen, high-density lipoprotein (HDL), hemoglobin, low-density lipoprotein cholesterol (LDL-D), and total proteins from their blood tests. In addition, APIP patients have decreased numbers in red cells but increased numbers in white blood cells and increased ratio of neutrophil/lymphocyte (N/L). Among these factors, N/LR, GGT, lipase, and HDL are significantly associated with APIP. This study suggests that the combination of those factors serve as a panel of indicators for early-onset prognosis of APIP.GGT, lipase, HDL, and N/LR can serve as a panel of factors to predict APIP. More case studies are important to further evaluate the predicting power of this panel factors in APIP.


Assuntos
Lipase/análise , Lipoproteínas HDL/análise , Linfócitos/citologia , Neutrófilos/citologia , Pancreatite/sangue , gama-Glutamiltransferase/sangue , Doença Aguda , Biomarcadores/sangue , China , Feminino , Humanos , Contagem de Leucócitos/métodos , Testes de Função Hepática , Pancreatite/diagnóstico , Pancreatite/etiologia , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/etiologia , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco
19.
Anal Chem ; 90(11): 6353-6356, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29756771

RESUMO

Lipoproteins are micelle-like assemblies that are key players in the pathogenesis of atherosclerosis. High-density lipoprotein (HDL), low-density lipoproteins (LDL), and very low density lipoprotein (VLDL) are the three major classes present in fasting plasma. Within each class, there is a broad size distribution with wide variations in protein and lipid content. The development of better metrics for cardiovascular risk is thought to depend on better characterization of lipoprotein subclasses. Using charge detection mass spectrometry (CDMS), the mass distributions of HDL, LDL, and VLDL have been directly measured for the first time. In the case of HDL, seven distinct subpopulations were resolved using a two-dimensional correlation of charge and mass. The resolved components are assigned to HDL particles containing different numbers of the key structural proteins apolipoprotein A-I and apolipoprotein A-II.


Assuntos
Lipoproteínas HDL/análise , Lipoproteínas LDL/análise , Lipoproteínas VLDL/análise , Espectrometria de Massas/métodos , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Lipoproteínas VLDL/sangue , Eletricidade Estática
20.
Med Sci Monit ; 24: 1688-1692, 2018 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-29563489

RESUMO

BACKGROUND We aimed to predict the abnormal LDL level by using TG, TC, HDL, and non-HDL in this study. MATERIAL AND METHODS Triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) data were obtained from the Laboratory Information System (LIS) for 4 years (Oct 1, 2013 to Sept 30, 2017) from among 34 270 healthy Chinese patients at Shuyang People's Hospital. TG, TC, HDL, and LDL (direct clearance method) were measured using a TBA2000FR biochemical analyzer. The non-HDL was calculated as TC minus HDL. Correlations between TG, TC, non-HDL, and LDL were analyzed using Spearman's rank correlation. Receiver operating characteristics (ROC) curve analysis was used to evaluate the predictive utility of TG, TC, and non-HDL for the abnormal LDL level (<130 mg/dL). RESULTS Both TC (r=0.870) and non-HDL (r=0.893) were significantly positively correlated with LDL. The area under curve of TC and non-HDL can be used to predict abnormal LDL levels. Optimal thresholds were 182.5 mg/Dl (4.72 mmol/L) for TC and 135.3 mg/Dl (3.50 mmol/L) for non-HDL. Based on these optimal thresholds, less than 0.5% and 0.4% of tests with elevated LDL were missed using TC and non-HDL, respectively, but the value of these missed LDL levels was not very high (<147.3 mg/dL). CONCLUSIONS If the value of non-HDL is less than 135.3 mg/Dl (3.50 mmol/L) and/or TC is less than 182.5 mg/Dl (4.72 mmol/L) for the apparently healthy populations, the LDL level will be less than 130 mg/Dl (3.36 mmol/L). TC and non-HDL can be used to predict the abnormal LDL level in apparently healthy populations.


Assuntos
Lipoproteínas LDL/análise , Adulto , Povo Asiático , Biomarcadores/sangue , China , Colesterol/análise , Colesterol/sangue , Feminino , Humanos , Lipídeos , Lipoproteínas HDL/análise , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Curva ROC , Triglicerídeos/análise , Triglicerídeos/sangue
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