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Front Immunol ; 12: 702425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489952


Antiphospholipid syndrome (APS) is a multisystem disorder characterized by thrombosis and/or recurrent fetal loss. This clinical phenotype heterogeneity may result in differences in response to treatment and prognosis. In this study, we aimed to identify primary thrombotic APS (TAPS) from primary obstetric APS (OAPS) using urine proteomics as a non-invasive method. Only patients with primary APS were enrolled in this study from 2016 to 2018 at a single clinical center in Shanghai. Urine samples from 15 patients with TAPS, 9 patients with OAPS, and 15 healthy controls (HCs) were collected and analyzed using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry analysis to identify differentially expressed proteins. Cluster analysis of urine proteomics identified differentiated proteins among the TAPS, OAPS, and HC groups. Urinary proteins were enriched in cytokine and cytokine receptor pathways. Representative secreted cytokines screened out (fold change >1.20, or <0.83, p<0.05) in these differentiated proteins were measured by enzyme-linked immunosorbent assay in a validation cohort. The results showed that the levels of C-X-C motif chemokine ligand 12 (CXCL12) were higher in the urine of patients with TAPS than in those with OAPS (p=0.035), while the levels of platelet-derived growth factor subunit B (PDGFB) were lower in patients with TAPS than in those with OAPS (p=0.041). In addition, correlation analysis showed that CXCL12 levels were positively correlated with immunoglobulin G anti-ß2-glycoprotein I antibody (r=0.617, p=0.016). Our results demonstrated that urinary CXCL12 and PDGFB might serve as potential non-invasive markers to differentiate primary TAPS from primary OAPS.

Nat Commun ; 12(1): 1487, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674561


Hyocholic acid (HCA) is a major bile acid (BA) species in the BA pool of pigs, a species known for its exceptional resistance to spontaneous development of diabetic phenotypes. HCA and its derivatives are also present in human blood and urine. We investigate whether human HCA profiles can predict the development of metabolic disorders. We find in the first cohort (n = 1107) that both obesity and diabetes are associated with lower serum concentrations of HCA species. A separate cohort study (n = 91) validates this finding and further reveals that individuals with pre-diabetes are associated with lower levels of HCA species in feces. Serum HCA levels increase in the patients after gastric bypass surgery (n = 38) and can predict the remission of diabetes two years after surgery. The results are replicated in two independent, prospective cohorts (n = 132 and n = 207), where serum HCA species are found to be strong predictors for metabolic disorders in 5 and 10 years, respectively. These findings underscore the association of HCA species with diabetes, and demonstrate the feasibility of using HCA profiles to assess the future risk of developing metabolic abnormalities.

Biomarcadores/sangue , Ácidos Cólicos/sangue , Ácidos Cólicos/urina , Doenças Metabólicas/diagnóstico , Adulto , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Fezes/química , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Sobrepeso/metabolismo , Estado Pré-Diabético/diagnóstico , Estudos Prospectivos
Nat Commun ; 10(1): 4971, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672964


Pu-erh tea displays cholesterol-lowering properties, but the underlying mechanism has not been elucidated. Theabrownin is one of the most active and abundant pigments in Pu-erh tea. Here, we show that theabrownin alters the gut microbiota in mice and humans, predominantly suppressing microbes associated with bile-salt hydrolase (BSH) activity. Theabrownin increases the levels of ileal conjugated bile acids (BAs) which, in turn, inhibit the intestinal FXR-FGF15 signaling pathway, resulting in increased hepatic production and fecal excretion of BAs, reduced hepatic cholesterol, and decreased lipogenesis. The inhibition of intestinal FXR-FGF15 signaling is accompanied by increased gene expression of enzymes in the alternative BA synthetic pathway, production of hepatic chenodeoxycholic acid, activation of hepatic FXR, and hepatic lipolysis. Our results shed light into the mechanisms behind the cholesterol- and lipid-lowering effects of Pu-erh tea, and suggest that decreased intestinal BSH microbes and/or decreased FXR-FGF15 signaling may be potential anti-hypercholesterolemia and anti-hyperlipidemia therapies.

Ácidos e Sais Biliares/metabolismo , Catequina/análogos & derivados , Alimentos e Bebidas Fermentados , Microbioma Gastrointestinal/efeitos dos fármacos , Hipercolesterolemia/metabolismo , Chá , Adulto , Amidoidrolases/metabolismo , Animais , Catequina/farmacologia , Ácido Quenodesoxicólico/metabolismo , Colesterol/metabolismo , Dieta Hiperlipídica , Transplante de Microbiota Fecal , Fatores de Crescimento de Fibroblastos/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/metabolismo , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Humanos , Íleo/efeitos dos fármacos , Íleo/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Metabolômica , Camundongos , Extratos Vegetais/farmacologia , RNA Ribossômico 16S , Receptores Citoplasmáticos e Nucleares/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/metabolismo , Transdução de Sinais , Adulto Jovem
J Matern Fetal Neonatal Med ; : 1-7, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30821182


OBJECTIVE: The aim of this study was to explore differences in serum Tau protein levels and neurodevelopmental prognoses of placental abruption or umbilical cord around neck with hypoxic-ischemic encephalopathy (HIE). METHODS: Forty neonates with moderate/severe HIE divided into placental abruption with HIE group (placental abruption with hypoxic-ischemic encephalopathy (PA-HIE) group) (n = 18) and umbilical cord around the neck with HIE group (umbilical cord around the neck with hypoxic-ischemic encephalopathy (UCAN-HIE) group) (n = 22). Healthy term newborns comprised the control group (n = 35). Serum Tau protein levels were measured using an enzyme-linked immunosorbent assay 24 hours (3.50 hours [1.00-24.00]) after birth. Neurodevelopment outcomes were assessed based on the Gesell Developmental Scale at 9 months of age. RESULTS: Serum Tau protein levels were significantly higher in 40 cases (1013 pg/ml [538.04-1190.42]) than in the control group (106.41 pg/ml [64.55-154.71], p = .0001). Serum Tau protein levels in the PA-HIE group (1024.46 pg/ml [657.88-1190.42]) were significantly higher than those in the UCAN-HIE group (892.78 pg/ml [538.04-1179.50], p = .0149). The development quotient score in the PA-HIE group (67.0 [47.0-90.0]) was significantly lower than that in the UCAN-HIE group (81.5 [52.6-100.0]) (p = .0028). The component ratio of neurodevelopmental retardation in the PA-HIE group (44.45%) was significantly higher than that in the UCAN-HIE group (22.73%) (X2 = 13.3138, p = .0013). CONCLUSIONS: Compared with the UCAN-HIE group, the serum Tau protein level and the component ratio of neurodevelopmental retardation were significantly higher in the PA-HIE group.

Anal Biochem ; 567: 106-111, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30557528


Different correlation detection methods have been specifically designed for the microbiome data analysis considering the compositional data structure and different sequencing depths. Along with the speedy development of omics studies, there is an increasing interest in discovering the biological associations between microbes and host metabolites. This raises the need of finding proper statistical methods that facilitate the correlation analysis across different omics studies. Here, we comprehensively evaluated six different correlation methods, i.e., Pearson correlation, Spearman correlation, Sparse Correlations for Compositional data (SparCC), Correlation inference for Compositional data through Lasso (CCLasso), Mutual Information Coefficient (MIC), and Cosine similarity methods, for the correlations detection between microbes and metabolites. Three simulated and two real-world data sets (from public databases and our lab) were used to examine the performance of each method regarding its specificity, sensitivity, similarity, accuracy, and stability with different sparsity. Our results indicate that although each method has its own pros and cons in different scenarios, Spearman correlation and MIC outperform the others with their overall performances. A strategic guidance was also proposed for the correlation analysis between microbe and metabolite.

Metaboloma , Microbiota , Modelos Estatísticos , Animais , Área Sob a Curva , Encéfalo/metabolismo , Análise por Conglomerados , Intestinos/microbiologia , Masculino , Curva ROC , Ratos , Ratos Wistar
Anal Chem ; 90(4): 2475-2483, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29353471


There is increased appreciation for the diverse roles of the microbiome-gut-brain axis on mammalian growth and health throughout the lifespan. Numerous studies have demonstrated that the gut microbiome and their metabolites are extensively involved in the communication between brain and gut. Association study of brain metabolome and gut microbiome is an active field offering large amounts of information on the interaction of microbiome, brain and gut but data size and complicated hierarchical relationships were found to be major obstacles to the formation of significant, reproducible conclusions. This study addressed a two-level strategy of brain metabolome and gut microbiome association analysis of male Wistar rats in the process of growth, employing several analytical platforms and various bioinformatics methods. Trajectory analysis showed that the age-related brain metabolome and gut microbiome had similarity in overall alteration patterns. Four high taxonomical level correlated pairs of "metabolite type-bacterial phylum", including "lipids-Spirochaetes", "free fatty acids (FFAs)-Firmicutes", "bile acids (BAs)-Firmicutes", and "Neurotransmitters-Bacteroidetes", were screened out based on unit- and multivariant correlation analysis and function analysis. Four groups of specific "metabolite-bacterium" association pairs from within the above high level key pairs were further identified. The key correlation pairs were validated by an independent animal study. This two-level strategy is effective in identifying principal correlations in big data sets obtained from the systematic multiomics study, furthering our understanding on the lifelong connection between brain and gut.

Encéfalo/metabolismo , Microbioma Gastrointestinal , Animais , Masculino , Metaboloma , Ratos