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1.
Comput Math Methods Med ; 2022: 8081673, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35707042

RESUMO

This study was aimed to explore magnetic resonance imaging (MRI) based on deep learning belief network model in evaluating serum bile acid profile and adverse perinatal outcomes of intrahepatic cholestasis of pregnancy (ICP) patients. Fifty ICP pregnant women diagnosed in hospital were selected as the experimental group, 50 healthy pregnant women as the blank group, and 50 patients with cholelithiasis as the gallstone group. Deep learning belief network (DLBN) was built by stacking multiple restricted Boltzmann machines, which was compared with the recognition rate of convolutional neural network (CNN) and support vector machine (SVM), to determine the error rate of different recognition methods on the test set. It was found that the error rate of deep learning belief network (7.68%) was substantially lower than that of CNN (21.34%) and SVM (22.41%) (P < 0.05). The levels of glycoursodeoxycholic acid (GUDCA), glycochenodeoxycholic acid (GCDCA), and glycocholic acid (GCA) in the experimental group were dramatically superior to those in the blank group (P < 0.05). Both the experimental group and the blank group had notable clustering of serum bile acid profile, and the experimental group and the gallstone group could be better distinguished. In addition, the incidence of amniotic fluid contamination, asphyxia, and premature perinatal infants in the experimental group was dramatically superior to that in the blank group (P < 0.05). The deep learning confidence model had a low error rate, which can effectively extract the features of liver MRI images. In summary, the serum characteristic bile acid profiles of ICP were glycoursodeoxycholic acid, glycochenodeoxycholic acid, and glycocholic acid, which had a positive effect on clinical diagnosis. The toxic effects of high concentrations of serum bile acids were the main cause of adverse perinatal outcomes and sudden death.


Assuntos
Aprendizado Profundo , Cálculos Biliares , Ácidos e Sais Biliares , Colestase Intra-Hepática , Feminino , Ácido Glicocólico , Humanos , Imageamento por Ressonância Magnética , Gravidez , Complicações na Gravidez , Resultado da Gravidez
2.
Hepatol Commun ; 6(9): 2391-2399, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35678016

RESUMO

Bile acids (BAs), major regulators of the gut microbiota, may play an important role in hepatobiliary cancer etiology. However, few epidemiologic studies have comprehensively examined associations between BAs and liver or biliary tract cancer. In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, we designed 1:1 matched, nested, case-control studies of primary liver cancer (n = 201 cases), fatal liver disease (n = 261 cases), and primary biliary tract cancer (n = 138 cases). Using baseline serum collected ≤30 years before diagnosis or death, we measured concentrations of 15 BAs with liquid chromatography-tandem mass spectrometry. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable conditional logistic regression models, adjusted for age, education, diabetes status, smoking, alcohol intake, and body mass index. We accounted for multiple comparisons using a false discovery rate (FDR) correction. Comparing the highest to the lowest quartile, seven BAs were positively associated with liver cancer risk, including taurocholic acid (TCA) (OR, 5.62; 95% CI, 2.74-11.52; Q trend < 0.0001), taurochenodeoxycholic acid (TCDCA) (OR, 4.77; 95% CI, 2.26-10.08; Q trend < 0.0001), and glycocholic acid (GCA) OR, 5.30; 95% CI, 2.41-11.66; Q trend < 0.0001), and 11 were positively associated with fatal liver disease risk, including TCDCA (OR, 9.65; 95% CI, 4.41-21.14; Q trend < 0.0001), TCA (OR, 7.45; 95% CI, 3.70-14.97; Q trend < 0.0001), and GCA (OR, 6.98; 95% CI, 3.32-14.68; Q trend < 0.0001). For biliary tract cancer, associations were generally >1 but not significant after FDR correction. Conjugated BAs were strongly associated with increased risk of liver cancer and fatal liver disease, suggesting mechanistic links between BA metabolism and liver cancer or death from liver disease.


Assuntos
Neoplasias do Sistema Biliar , Neoplasias Hepáticas , Ácidos e Sais Biliares , Neoplasias do Sistema Biliar/epidemiologia , Ácido Glicocólico , Humanos , Neoplasias Hepáticas/epidemiologia , Estudos Prospectivos , Ácido Taurocólico
3.
Molecules ; 27(9)2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35566380

RESUMO

To develop new therapeutic molecules, it is essential to understand the biological effects and targets of clinically relevant compounds. In this article, we describe the extraction and characterization of two alkaloids from the roots of Isolona hexaloba-curine and guattegaumerine. The effect of these alkaloids on the multidrug efflux pump ABCB1 (MDR1/P-Glycoprotein) and their antiproliferative properties were studied. Compared to verapamil, a widely used inhibitor of P-gp, curine and guattegaumerine were found to be weak inhibitors of MDR1/P-Glycoprotein. The highest inhibition of efflux produced by verapamil disappeared in the presence of curine or guattegaumerine as competitors, and the most pronounced effect was achieved with curine. Altogether, this work has provided new insights into the biological effects of these alkaloids on the rat Mdr1b P-gp efflux mechanism and would be beneficial in the design of potent P-gp inhibitors.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Benzilisoquinolinas , Subfamília B de Transportador de Cassetes de Ligação de ATP , Animais , Ácido Glicocólico , Isoquinolinas , Ratos , Rodaminas , Verapamil/farmacologia
4.
Arch Oral Biol ; 139: 105429, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35462184

RESUMO

OBJECTIVES: To identify the bile acids in the saliva of patients with and without gastroesophageal reflux disease (GERD), and evaluate their effect on tooth surface. DESIGN: A cross-sectional study involved 26 GERD patients and 40 controls without GERD. Dental erosions were identified, saliva was collected and analyzed with chromatography for bile acid identification. An in vitro study assessed the effect of enamel exposition to taurocholic acid in concentrations of 1 µM, 10 µM, and a mixture of taurocholic acid and glycocholic acid at 10 µM on enamel microhardness, calcium release, and surface topography. RESULTS: Salivary bile acids were analyzed from 22 GERD patients and 40 controls. All these participants presented taurocholic acid and glycocholic acid in the saliva. The salivary amount of taurocholic acid was greater than glycocholic acid in both GERD patients (area under the curve: 7946 vs. 1361; p < 0.001) and controls (10,815 vs. 1290; p < 0.001). The salivary amount of taurocholic acid was greater in controls than in GERD patients (10,815 vs. 7946; p < 0.001). Dental erosion was more prevalent in GERD patients than in controls (27% vs. 7%; p = 0.041). In the GERD presence, the amount of glycocholic acid was greater in patients with dental erosion (1777 vs. 1239; p = 0.041). Enamel exposed to taurocholic acid at 10 µM, combined or not with glycocholic acid, had their microhardness increased, accompanied by calcium release, with no changes in surface topography. CONCLUSIONS: Taurocholic acid was the predominant salivary bile acid, particularly in controls without GERD. This bile acid had no deleterious effect on the enamel structure.


Assuntos
Refluxo Gastroesofágico , Erosão Dentária , Ácidos e Sais Biliares , Cálcio , Estudos Transversais , Ácido Glicocólico , Humanos , Ácido Taurocólico
5.
Int J Pharm ; 617: 121589, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35176336

RESUMO

Bile acid transporter-targeting has been proven to be an effective strategy to improve drug delivery to hepatocytes and enterocytes. With increasing discoveries of bile acid transporter expression on tumor cells, bile acid-modified anticancer drugs are gradually attaining interests. In our previous study, we confirmed the efficacy of glycocholic acid-conjugated polystyrene nanoparticles (GCPN) on apical sodium bile acid transporter (ASBT)-expressed SK-BR-3 cells. However, the transport mechanisms remain unknown, due to the nanosized carriers are unlikely to be pumped through the narrow cavities of ASBT. To clarify their transport pathways, in this article, pharmacological inhibition and gene knocking-down studies were performed, which revealed that GCPN were primarily internalized via non-caveolar lipid raft-mediated endocytosis. Proteomics was analyzed to explore the in-depth mechanisms. In total 561 proteins were identified and statistical overrepresentation test was used to analyze the gene ontology (GO) upregulated pathways based on the highly expressed proteins. It was found that multiple pathways were upregulated and might coordinate to assist the location of the GCPN-ASBT complex and the recycling of ASBT. Among the highly expressed proteins, myelin and lymphocyte protein 2 (MAL2) was selected and confirmed to colocalize with GCPN, which further supported the lipid raft-mediated process. These findings will help set up a platform for designing the bile acid-modified nanomedicines and regulating their transport to improve their anticancer efficacy.


Assuntos
Neoplasias da Mama , Nanopartículas , Simportadores , Ácidos e Sais Biliares , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular , Feminino , Ácido Glicocólico , Humanos , Microdomínios da Membrana/metabolismo , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina/metabolismo , Transportadores de Ânions Orgânicos Dependentes de Sódio , Simportadores/metabolismo
6.
J Med Virol ; 94(6): 2714-2726, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35199373

RESUMO

Dynamic changes in metabolites may affect liver disease progression, and provide new methods for predicting liver damage. We used ultra-performance liquid chromatography-mass spectroscopy to assess serum metabolites in healthy controls (HC), and patients with acute hepatitis E (AHE) or hepatitis E virus acute liver failure (HEV-ALF). The principal component analysis, partial least squares discriminant analysis, and discriminant analysis of orthogonal projections to latent structures models illustrated significant differences in the metabolite components between AHE patients and HCs, or between HEV-ALF and AHE patients. In pathway enrichment analysis, we further identified two altered pathways, including linoleic acid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis, when comparing AHE patients with HCs. Linoleic acid metabolism and porphyrin and chlorophyll metabolism pathways were significantly different in HEV-ALF when compared with AHE patients. The discriminative performances of differential metabolites showed that taurocholic acid, glycocholic acid, glycochenodeoxycholate-3-sulfate, and docosahexaenoic acid could be used to distinguish HEV-ALF from AHE patients. The serum levels of glycocholic acid, taurocholic acid, deoxycholic acid glycine conjugate, and docosahexaenoic acid were associated with the prognosis of HEV-ALF patients. Dynamic changes in serum metabolites were associated with AHE infection and severity. The identified metabolites can be used to diagnose and predict the prognosis of HEV-ALF.


Assuntos
Vírus da Hepatite E , Hepatite E , Doença Aguda , Ácidos Docosa-Hexaenoicos , Ácido Glicocólico , Humanos , Ácido Linoleico , Ácido Taurocólico
7.
Front Immunol ; 12: 733225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721396

RESUMO

Background: Intrahepatic cholestasis of pregnancy (ICP) usually occurs in the third trimester and is associated with increased risks in fetal complications. Currently, the exact mechanism of this disease is unknown. The purpose of this study was to develop potential biomarkers for the diagnosis and prediction of ICP. Methods: We enrolled 40 pregnant women diagnosed with ICP and 40 healthy pregnant controls. The number of placental samples and serum samples between the two groups was 10 and 40 respectively. Ultra-performance liquid chromatography tandem high-resolution mass spectrometry was used to analyze placental metabolomics. Then, we verified the differentially expressed proteins and metabolites, both placental and blood serum, in the first, second, and third trimesters. Results: Metabolomic analysis of placental tissue revealed that fatty acid metabolism and primary bile acid biosynthesis were enriched. In the integrated proteomic and metabolomic analysis of placental tissue, peroxisomal acyl-CoA oxidase 1 (ACOX1), L-palmitoylcarnitine, and glycocholic acid were found to be three potential biomarkers. In a follow-up analysis, expression levels of both placental and serum ACOX1, L-palmitoylcarnitine, and glycocholic acid in both placenta and serum were found to be significantly higher in third-trimester ICP patients; the areas under the ROC curves were 0.823, 0.896, and 0.985, respectively. Expression levels of serum ACOX1, L-palmitoylcarnitine, and glycocholic acid were also significantly higher in first- and second-trimester ICP patients; the areas under the ROC curves were 0.726, 0.657, and 0.686 in the first trimester and 0.718, 0.727, and 0.670 in the second trimester, respectively. Together, levels of the three aforementioned biomarkers increased the value for diagnosing and predicting ICP (AUC: 0.993 for the third, 0.891 for the second, and 0.932 for the first trimesters). Conclusions: L-palmitoylcarnitine, ACOX1, and glycocholic acid levels taken together may serve as a new biomarker set for the diagnosis and prediction of ICP.


Assuntos
Colestase Intra-Hepática/sangue , Metaboloma , Metabolômica , Placenta/metabolismo , Complicações na Gravidez/sangue , Proteoma , Proteômica , Acil-CoA Oxidase/sangue , Adulto , Biomarcadores/sangue , Colestase Intra-Hepática/diagnóstico , Cromatografia Líquida , Feminino , Ácido Glicocólico/sangue , Humanos , Palmitoilcarnitina/sangue , Valor Preditivo dos Testes , Gravidez , Complicações na Gravidez/diagnóstico , Espectrometria de Massas em Tandem , Adulto Jovem
8.
J Healthc Eng ; 2021: 3911998, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540186

RESUMO

Objective: To see whether serum glycocholic acid (CG) and total bile acids (TBA) can predict maternal and perinatal outcomes in pregnant women with intrahepatic cholestasis (ICP). Method: The observation group consisted of 80 women with ICP who were treated in our hospital, whereas the control group consisted of 50 ordinary women who were also treated at our hospital at the same time. The levels of CG and TBA in the two groups were determined independently, and the differences in poor perinatal outcomes were compared. Finally, the predictive diagnostic value of CG and TBA for poor perinatal outcomes in ICP mothers was displayed using the Spearman correlation between CG and TBA and Apgar. The maternal CG and TBA levels in the observation group were substantially higher than in the control group (P0.05). The observation group had more significant maternal-fetal discomfort, neonatal asphyxia, preterm birth, and perinatal death than the control group (P0.05). The risk of poor perinatal outcomes in ICP mothers rose when TBA and CG levels increased (P0.05). Apgar ratings were inversely associated with CG and TBA (r = -0.8251 and r = -0.5969, respectively, P0.05). The CG and TBA diagnostic AUCs for unfavorable perinatal outcomes in ICP mothers were (P0.05). Conclusion: CG and TBA have a high diagnostic value for ICP and may better predict and identify poor prenatal outcomes. It is suitable for clinical use.


Assuntos
Colestase Intra-Hepática , Nascimento Prematuro , Ácidos e Sais Biliares , Colestase Intra-Hepática/diagnóstico , Feminino , Ácido Glicocólico , Humanos , Recém-Nascido , Gravidez , Complicações na Gravidez
9.
Sci Rep ; 11(1): 17788, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493738

RESUMO

Bile acid profiles are altered in obese individuals with asthma. Thus, we sought to better understand how obesity-related systemic changes contribute to lung pathophysiology. We also test the therapeutic potential of nitro-oleic acid (NO2-OA), a regulator of metabolic and inflammatory signaling pathways, to mitigate allergen and obesity-induced lung function decline in a murine model of asthma. Bile acids were measured in the plasma of healthy subjects and individuals with asthma and serum and lung tissue of mice with and without allergic airway disease (AAD). Lung function, indices of inflammation and hepatic bile acid enzyme expression were measured in obese mice with house dust mite-induced AAD treated with vehicle or NO2-OA. Serum levels of glycocholic acid and glycoursodeoxycholic acid clinically correlate with body mass index and airway hyperreactivity whereas murine levels of ß-muricholic acid and tauro-ß-muricholic acid were significantly increased and positively correlated with impaired lung function in obese mice with AAD. NO2-OA reduced murine bile acid levels by modulating hepatic expression of bile acid synthesis enzymes, with a concomitant reduction in small airway resistance and tissue elastance. Bile acids correlate to body mass index and lung function decline and the signaling actions of nitroalkenes can limit AAD by modulating bile acid metabolism, revealing a potential pharmacologic approach to improving the current standard of care.


Assuntos
Asma/metabolismo , Asma/fisiopatologia , Ácidos e Sais Biliares/metabolismo , Ácidos Graxos/fisiologia , Pulmão/fisiopatologia , Nitrocompostos/uso terapêutico , Obesidade/metabolismo , Ácidos Oleicos/uso terapêutico , Adolescente , Adulto , Animais , Antiasmáticos/uso terapêutico , Antígenos de Dermatophagoides/toxicidade , Asma/tratamento farmacológico , Asma/etiologia , Dieta Hiperlipídica/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Ácidos Graxos/química , Feminino , Volume Expiratório Forçado , Ácido Glicocólico/sangue , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/fisiopatologia , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/tratamento farmacológico , Hipersensibilidade Respiratória/metabolismo , Magreza , Ácido Ursodesoxicólico/análogos & derivados , Ácido Ursodesoxicólico/sangue , Capacidade Vital , Adulto Jovem
10.
Anal Bioanal Chem ; 413(23): 5733-5742, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34476526

RESUMO

Palladium nanoparticles (PdNPs) are composed mainly of inert noble metals, and their outstanding properties have attracted wide attention. PdNPs are not only capable of mimicking the oxidase-like characteristics of natural bio-enzymes, but they also present a clear black band in the test zone. In this work, the synthesized PdNPs promoted a transformation of colorless tetramethylbenzidine (TMB) to a blue oxidation product of TMB, providing a Km value of 0.09 mM for TMB, and revealing the good catalytic performance of the synthesized PdNPs. For both signal generation and amplification, PdNPs effectively replaced natural bio-enzymes as a new labeling tag. Thus, the PdNP-based enzyme-free single-step immunoassays were successfully developed for efficient and sensitive detection of glycocholic acid (GCA). Under optimal conditions, a noticeable linear relationship was identified by the enzyme-linked immunosorbent assay (ELISA) over a range of 8-2390 ng/mL, while the visual limit of detection (vLOD) in the constructed lateral flow immunoassay (LFA) was 10 ng/mL for GCA. The recovery rate in spiked urine samples obtained by the ELISA ranged from 84.2 to 117.9%, which was consistent with the results in LFA. The present work demonstrates the potential of PdNPs as labeling matrices in enzyme-free single-step immunoassays.


Assuntos
Ácido Glicocólico/análise , Imunoensaio/métodos , Nanopartículas Metálicas/química , Paládio/química , Catálise , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Ácido Glicocólico/urina , Humanos , Limite de Detecção
11.
Sci Rep ; 11(1): 11642, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34079030

RESUMO

To understand the characteristic of changes of serum metabolites between healthy people and patients with hepatitis B virus (HBV) infection at different stages of disease, and to provide reference metabolomics information for clinical diagnosis of liver disease patients. 255 patients with different stages of HBV infection were selected. 3 mL blood was collected from each patient in the morning to detect differences in serum lysophosphatidylcholine, acetyl-L-carnitine, oleic acid amide, and glycocholic acid concentrations by UFLC-IT-TOF/MS. The diagnostic values of four metabolic substances were evaluated by receiver operating characteristic (ROC) curve. The results showed that the optimal cut-off value of oleic acid amide concentration of the liver cirrhosis and HCC groups was 23.6 mg/L, with a diagnostic sensitivity of 88.9% and specificity of 70.6%. The diagnostic efficacies of the three substances were similar in the hepatitis and HCC groups, with an optimal cut-off value of 2.04 mg/L, and a diagnostic sensitivity and specificity of 100% and 47.2%, respectively. The optimal cut-off value of lecithin of the HBV-carrier and HCC groups was 132.85 mg/L, with a diagnostic sensitivity and specificity of 88.9% and 66.7%, respectively. The optimal cut-off value of oleic acid amide of the healthy and HCC groups was 129.03 mg/L, with a diagnostic sensitivity and specificity of 88.4% and 83.3%, respectively. Lysophosphatidylcholine, acetyl-L-carnitine, and oleic acid amide were potential metabolic markers of HCC. Among them, lysophosphatidylcholine was low in the blood of HCC patients, and its diagnostic efficacy was better than that of acetyl-L-carnitine and oleic acid amide, providing reference metabolomics information in clinical diagnosis and future research.


Assuntos
Acetilcarnitina/sangue , Ácido Glicocólico/sangue , Hepatite B Crônica/diagnóstico , Hepatite C Crônica/diagnóstico , Cirrose Hepática/diagnóstico , Lisofosfatidilcolinas/sangue , Ácidos Oleicos/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Hepatite B Crônica/sangue , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Hepatite C Crônica/sangue , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
12.
Biomaterials ; 275: 120944, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34153783

RESUMO

The oral administration route is popular with T2DM patients because they need convenience in lifelong medication. At present, oral Exenatide is not available on the market and therefore the relevant studies are valuable. Herein, we constructed a novel dual cholic acid-functionalized nanoparticle for oral delivery of Exenatide, which was based on the functionalized materials of deoxycholic acid-low molecular weight protamine and glycocholic acid-poly (ethylene glycol)-b-polysialic acid. The hydrophobic deoxycholic acid strengthened the nanoparticles and the hydrophilic glycolic acid targeted to specific transporter. We first condensed Exenatide-Zn2+ complex with deoxycholic acid-low molecular weight protamine to prepare nanocomplexes with ζ-potentials of +8 mV and sizes of 95 nm. Then, we used glycocholic acid-poly (ethylene glycol)-b-polysialic acid copolymers masking the positive charge of nanocomplexes to prepare nanoparticles with negative charges of -22 mV and homogeneous sizes of 140 nm. As a result, this dual cholic acid-functionalized nanoparticle demonstrated enhanced uptake and transport of Exenatide, and a special targeting to apical sodium-dependent cholic acid transporter in vitro. Moreover, in vivo studies showed that the nanoparticle effectively accumulated in distal ileum, raised the plasma concentration of Exenatide, prolonged hypoglycemic effect, reduced blood lipid levels, and lightened organ lesions.


Assuntos
Diabetes Mellitus , Exenatida/administração & dosagem , Hipoglicemiantes , Administração Oral , Preparações de Ação Retardada/administração & dosagem , Ácido Desoxicólico , Diabetes Mellitus/tratamento farmacológico , Ácido Glicocólico , Humanos , Íleo , Nanopartículas , Zinco
13.
Clin Lab ; 67(6)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34107618

RESUMO

BACKGROUND: Reference intervals of clinical laboratory indexes are the basis of interpretation of test results. While intrahepatic cholestasis of pregnancy (ICP) could severely threaten maternal and fetal health, reference intervals of the biomarkers serum total bile acids (TBA) and glycocholic acid (GCA) are unsatisfactory. The purpose of this study was to derive gestational age-specific reference intervals for serum TBA and GCA in a Chinese population to promote early diagnosis of ICP. METHODS: A total of 416 healthy pregnant Chinese were recruited and divided into three groups by gestational age: 140 in the first trimester (1 - 13 weeks) group, 136 in the second trimester (14 - 27 weeks) group, and 140 in the third trimester (≥ 28 weeks) group. Serum TBA and GCA levels were measured respectively by cyclic enzymatic method and latex enhanced immune turbidimetry. Reference intervals were calculated with non-parametric method. RESULTS: The reference intervals of serum TBA are 0.90 - 6.60 µmol/L, 1.20 - 9.10 µmol/L, and 1.50 - 8.90 µmol/L respectively in the first, second, and third trimester. The reference intervals of serum GCA are 0.24 - 1.14 µg/mL in the first and second trimesters (combined) and 0.00 - 2.04 µg/mL in the third trimester. CONCLUSIONS: Gestational age-specific reference intervals of serum TBA and GCA for pregnant Chinese were derived in strict accordance with CLSI C28-A3 guidelines, which will be valuable for early diagnosis of ICP.


Assuntos
Colestase Intra-Hepática , Complicações na Gravidez , Idoso de 80 Anos ou mais , Ácidos e Sais Biliares , China , Feminino , Idade Gestacional , Ácido Glicocólico , Humanos , Gravidez , Valores de Referência
14.
Biomolecules ; 11(5)2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922434

RESUMO

We previously demonstrated that the bile acid taurocholic acid (TCA) inhibits features of age-related macular degeneration (AMD) in vitro. The purpose of this study was to determine if the glycine-conjugated bile acids glycocholic acid (GCA), glycodeoxycholic acid (GDCA), and glycoursodeoxycholic acid (GUDCA) can protect retinal pigment epithelial (RPE) cells against oxidative damage and inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis in choroidal endothelial cells (CECs). Paraquat was used to induce oxidative stress and disrupt tight junctions in HRPEpiC primary human RPE cells. Tight junctions were assessed via transepithelial electrical resistance and ZO-1 immunofluorescence. GCA and GUDCA protected RPE tight junctions against oxidative damage at concentrations of 100-500 µM, and GDCA protected tight junctions at 10-500 µM. Angiogenesis was induced with VEGF in RF/6A macaque CECs and evaluated with cell proliferation, cell migration, and tube formation assays. GCA inhibited VEGF-induced CEC migration at 50-500 µM and tube formation at 10-500 µM. GUDCA inhibited VEGF-induced CEC migration at 100-500 µM and tube formation at 50-500 µM. GDCA had no effect on VEGF-induced angiogenesis. None of the three bile acids significantly inhibited VEGF-induced CEC proliferation. These results suggest glycine-conjugated bile acids may be protective against both atrophic and neovascular AMD.


Assuntos
Ácidos e Sais Biliares/metabolismo , Neovascularização Patológica/prevenção & controle , Epitélio Pigmentado da Retina/metabolismo , Inibidores da Angiogênese/farmacologia , Animais , Técnicas de Cultura de Células , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Corioide/metabolismo , Células Endoteliais/metabolismo , Glicina/metabolismo , Ácido Glicocólico/farmacologia , Ácido Glicodesoxicólico/farmacologia , Humanos , Macaca mulatta , Neovascularização Patológica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Junções Íntimas/metabolismo , Ácido Ursodesoxicólico/análogos & derivados , Ácido Ursodesoxicólico/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Degeneração Macular Exsudativa/metabolismo
15.
Anal Methods ; 13(16): 1919-1924, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33913980

RESUMO

The concentration of glycocholic acid (GCA) in urine and blood is an important biomarker for liver cancer. Monitoring of GCA depends to a large extent on the availability of appropriate analytical techniques. In this work, based on the immobilization of GCA-OVA onto the sensor chip surface, a label-free competitive inhibition immunoassay for the determination of GCA with the surface plasmon resonance (SPR) technique was developed. The proposed SPR immunosensor is simple to prepare, recyclable and exhibits excellent sensitivity to GCA (a linear range of 13.3-119.4 ng mL-1 and a limit of detection (LOD) of 2.5 ng mL-1), which was 14 times lower than that of the traditional immunoassay. Excellent recoveries and correlation between these two methods were observed (R2 = 0.995). Hence, it can be proved that the SPR immunosensor could be used to achieve rapid and sensitive quantitative detection of GCA in real urine samples and meet clinical needs.


Assuntos
Técnicas Biossensoriais , Ressonância de Plasmônio de Superfície , Ácido Glicocólico , Imunoensaio , Limite de Detecção
16.
Neuroreport ; 32(6): 415-422, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33788810

RESUMO

BACKGROUND: To identify the potent metabolic biomarkers and time of injury of traumatic brain injured (TBI). METHODS: A total of 70 Sprague-Dawley rats were used to establish the TBI model in this study. The serum was collected at 3 h, 6 h, 12 h, 24 h, 3 days and 7 days after surgery. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was performed to analyze metabolic changes in the serum of the TBI rats from different groups. The differences between the metabolic profiles of the rats in seven groups were analyzed using partial least squares discriminant analysis. RESULTS: Metabolic profiling revealed significant differences between the sham-operated and other groups. A total of 49 potential TBI metabolite biomarkers were identified between the sham-operated group and the model groups at different time points. Among them, six metabolites (methionine sulfone, kynurenine, 3-hydroxyanthranilic acid, 3-Indolepropionic acid, citric acid and glycocholic acid) were identified as biomarkers of TBI to estimate the injury time. CONCLUSION: Using metabolomic analysis, we identified new TBI serum biomarkers for accurate detection and determination of the timing of TBI injury.


Assuntos
Ácido 3-Hidroxiantranílico/metabolismo , Lesões Encefálicas Traumáticas/sangue , Ácido Cítrico/sangue , Ácido Glicocólico/sangue , Indóis/sangue , Cinurenina/sangue , Metionina/análogos & derivados , Propionatos/sangue , Animais , Lesões Encefálicas Traumáticas/metabolismo , Cromatografia Líquida , Masculino , Espectrometria de Massas , Metaboloma , Metabolômica , Metionina/sangue , Ratos , Ratos Sprague-Dawley
17.
J Phys Chem B ; 125(2): 612-624, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33417461

RESUMO

Increased total cholesterol is a major cause of serious heart ailments leading to an estimated 3 million deaths annually throughout the world. Understanding the flocculation behavior of small lipids is thus quintessential. Nucleation, small-angle scattering, and dynamical behavior of lipids and analogues like cholesterol (CHL), cholesteryl hemisuccinate (CHM), and glycocholic acid (GHL) are studied in water by molecular dynamics simulation. The study shows a distinct aggregation behavior of these physiologically relevant molecules owing to a systematic gradation in their non-bonding interactions with solvents and near neighbors. Spontaneous self-assemblies formed during simulation are observed to have different stability, aggregation patterns, and dynamics depending crucially on the nature of the hydrophobic/hydrophilic tails. With increasing hydrophilicity, in the order CHL < CHM < GHL, the aggregates become breakable and less compact, often interposed by water molecules in the interstitial spaces between the lipids. Small-angle scattering data obtained from our simulations provide insights toward the structural integrity and shape of the aggregates formed. Unique features are noticed while following the time evolution of the packing of the nucleated assemblies from the solution phase in terms of local density and molecular orientation. As hydrophilicity increases from CHL to GHL, the packing becomes progressively erratic with diverse angles between the molecular vectors. Surface electrostatic potential calculation indicates drastic increase in positive surface charge from CHL to CHM, which has strong implication in water and ion transport through membranes. These observations can be further correlated to comprehend the flocculation of cholesterol and bile acids in the human body.


Assuntos
Ésteres do Colesterol , Ácido Glicocólico , Colesterol , Humanos , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Água
18.
J Dairy Sci ; 104(2): 1524-1530, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33246627

RESUMO

Effects of chemical structure, concentration, and pH on antimicrobial activity of conjugated bile acids were investigated in 4 strains of lactobacilli. Considerable differences were observed in the antimicrobial activity between the 6 human conjugated bile acids, including glycocholic acid, taurocholic acid, glycodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid, and taurochenodeoxycholic acid. Glycodeoxycholic acid and glycochenodeoxycholic acid generally showed significantly higher antimicrobial activity against the lactobacilli, but glycocholic acid and taurocholic acid exhibited the significantly lower antimicrobial activity. Glycochenodeoxycholic acid was selected for further analysis, and the results showed its antimicrobial activity was concentration-dependent, and there was a significantly negative linear correlation (R2 > 0.98) between bile-antimicrobial index and logarithmic concentration of the bile acid for each strain of lactobacilli. Additionally, the antimicrobial activity of glycochenodeoxycholic acid was also observed to be pH-dependent, and it was significantly enhanced with the decreasing pH, with the result that all the strains of lactobacilli were unable to grow at pH 5.0. In conclusion, chemical structure, concentration, and pH are key factors influencing antimicrobial activity of conjugated bile acids against lactobacilli. This study provides theoretical guidance and technology support for developing a scientific method for evaluating the bile tolerance ability of potentially probiotic strains of lactobacilli.


Assuntos
Anti-Infecciosos/farmacologia , Ácidos e Sais Biliares/farmacologia , Lactobacillus/efeitos dos fármacos , Animais , Anti-Infecciosos/química , Ácidos e Sais Biliares/química , Ácido Glicoquenodesoxicólico/química , Ácido Glicoquenodesoxicólico/farmacologia , Ácido Glicocólico/química , Ácido Glicocólico/farmacologia , Ácido Glicodesoxicólico/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Probióticos , Ácido Tauroquenodesoxicólico/química , Ácido Tauroquenodesoxicólico/farmacologia , Ácido Taurocólico/química , Ácido Taurocólico/farmacologia , Ácido Taurodesoxicólico/química , Ácido Taurodesoxicólico/farmacologia
19.
Ann Hepatol ; 20: 100253, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32949785

RESUMO

INTRODUCTION/AIMS: Liver fibrosis assessment is a key issue in the evaluation of nonalcoholic fatty liver disease (NAFLD) patients. In the present study, we aimed to validate a noninvasive marker panel to assess significant and advanced fibrosis in these patients. METHOD: 126 biopsy-proven NAFLD patients were included. NAFLD diagnosis was based on histological criteria. Fibrosis stages were determined according to NASH-Clinical Research Network criteria. Clinical and laboratorial data were collected during the interval of three months before or after liver biopsy. Histological fibrosis stages were classified as significant fibrosis (F2-F4) and advanced fibrosis (F3-F4). Five serum biomarkers [hyaluronic acid (HA), collagen type IV (cIV), procollagen type III (PC III), laminin (LN) and cholylglycine (CG)] were assessed by chemiluminescence immunoassays. RESULTS: Most patients were female (61.61%), mean age: 55.7 ±â€¯9.13 years old and mean BMI was 32.1 ±â€¯5.9 kg/m2. Prevalence of diabetes, dyslipidemia, arterial hypertension, and metabolic syndrome was 68.75%, 82.29%, 63.54% and 81.05%, respectively. Patients with cIV above 30 ng/mL had a 5.57-times (IC: 1.86-16.69) the chance of having significant fibrosis and 7.61-times (IC: 2.27-25.54) the chance of having advanced fibrosis versus patients with values below 30 ng/mL. HA, PC III, LN and CG did not detect the presence of significant and advanced fibrosis. The AUROC of clV for detection of significant (0.718) and advanced fibrosis (0.791) was better than that of other serum biomarkers. CONCLUSION: Type 4 collagen could predict the presence of significant and advanced fibrosis in NAFLD patients and it would be a useful tool in routine clinical practice.


Assuntos
Colágeno Tipo IV/sangue , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Colágeno Tipo III/sangue , Feminino , Ácido Glicocólico/sangue , Humanos , Ácido Hialurônico/sangue , Laminina/sangue , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações
20.
Mol Pharm ; 17(11): 4346-4353, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33064945

RESUMO

Here, we describe the absorption pathways of nanoparticles whose surface is modified with bile acid and present environmental factors that influence oral bioavailability (BA) from the gastrointestinal tract (GIT). The approach utilized 100 nm sized fluorescence-labeled, carboxylated polystyrene nanoparticles (CPN) conjugated with glycocholic acid (G/CPN) to exclude potential artifacts, if existing, and instability issues in evaluating the transit of G/CPN in the GIT and measuring BA. The in vitro study using SK-BR-3 that expresses the apical sodium bile acid transporter showed that once G/CPN is internalized, it stayed 2.9 times longer in the cells than CPN, indirectly suggesting that G/CPN takes intracellular trafficking pathways different from CPN in SK-BR-3 cells. In a Caco-2 cell monolayer, G/CPN passed through the monolayer without damaging the tight junction. G/CPN, when administered orally in rodents, showed sustained transit time in the GIT for at least 4 h and was absorbed into the intestinal lymphatic system and circulated into the blood. Ingestion of food before and after oral administration delays G/CPN absorption and decreases BA. A decrease in gastrointestinal motility by anesthetic condition increased the relative BA of G/CPN by up to 74%. Thus, the oral BA of G/CPN can be optimized by taking food ingestion and gastrointestinal motility into account.


Assuntos
Portadores de Fármacos/química , Ácido Glicocólico/administração & dosagem , Ácido Glicocólico/farmacocinética , Absorção Intestinal/efeitos dos fármacos , Vasos Linfáticos/metabolismo , Nanopartículas/química , Transdução de Sinais/efeitos dos fármacos , Administração Oral , Animais , Disponibilidade Biológica , Células CACO-2 , Humanos , Vasos Linfáticos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Poliestirenos/química , Ratos , Ratos Sprague-Dawley , Junções Íntimas/efeitos dos fármacos , Distribuição Tecidual
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