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1.
Rev Med Liege ; 79(1): 34-40, 2024 Jan.
Artigo em Francês | MEDLINE | ID: mdl-38223968

RESUMO

The use of skin substitutes in burn surgery and in the treatment of acute or chronic wounds is constantly evolving. For years, scientists have been researching skin substitutes that can be used in place of autologous skin. New products are regularly developed and approved for clinical use. In this article, we take a look at the skin substitutes most commonly used in Europe and briefly summarize the current clinical experience of our centre.


L'utilisation des substituts cutanés dans la chirurgie des grands brûlés et dans le traitement des plaies aiguës ou chroniques est en constante évolution. Depuis des années, les scientifiques recherchent des substituts cutanés qui peuvent être utilisés à la place de la peau autologue. De nouveaux produits sont régulièrement développés et approuvés pour l'utilisation clinique. Dans cet article, nous examinons les substituts cutanés les plus utilisés en Europe et résumons brièvement l'expérience pratique de notre centre.


Assuntos
Pele Artificial , Humanos , Engenharia Tecidual , Cicatrização , Pele/lesões , Europa (Continente)
2.
Int J Mol Sci ; 24(14)2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37511184

RESUMO

Cow's milk protein allergy (CMPA) is a prevalent food allergy among infants and young children. We conducted a randomized, multicenter intervention study involving 194 non-breastfed infants with CMPA until 12 months of age (clinical trial registration: NCT03085134). One exploratory objective was to assess the effects of a whey-based extensively hydrolyzed formula (EHF) supplemented with 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) on the fecal microbiome and metabolome in this population. Thus, fecal samples were collected at baseline, 1 and 3 months from enrollment, as well as at 12 months of age. Human milk oligosaccharides (HMO) supplementation led to the enrichment of bifidobacteria in the gut microbiome and delayed the shift of the microbiome composition toward an adult-like pattern. We identified specific HMO-mediated changes in fecal amino acid degradation and bile acid conjugation, particularly in infants commencing the HMO-supplemented formula before the age of three months. Thus, HMO supplementation partially corrected the dysbiosis commonly observed in infants with CMPA. Further investigation is necessary to determine the clinical significance of these findings in terms of a reduced incidence of respiratory infections and other potential health benefits.


Assuntos
Microbioma Gastrointestinal , Hipersensibilidade a Leite , Criança , Feminino , Animais , Bovinos , Humanos , Lactente , Pré-Escolar , Leite Humano , Oligossacarídeos , Suplementos Nutricionais , Metaboloma , Fórmulas Infantis/química
3.
Rev Med Liege ; 78(11): 604-609, 2023 Nov.
Artigo em Francês | MEDLINE | ID: mdl-37955288

RESUMO

Acute management in emergency department of pediatric burns is challenging for clinicians. Many of these burns are minor and can be treated on an outpatient basis. However, moderate and severe burns require hospitalization. Although management principles are similar between children and adults polytrauma, children have differences in their pathophysiological response to burn injury. Understanding these differences is essential to optimize the patient care. Particularities of acute management of pediatric burns are discussed in this article.


La prise en charge aux urgences d'un enfant brûlé est un défi pour les cliniciens. Souvent superficielles, la plupart des brûlures peuvent être traitées en ambulatoire. Cependant, les brûlures modérées et sévères nécessitent une hospitalisation. Bien que la prise en charge repose sur des principes similaires à ceux des patients polytraumatisés, les enfants présentent des différences dans la réponse physiopathologique à la brûlure. Tenir compte de ces différences est essentiel pour une prise en charge optimale. Les spécificités des modalités thérapeutiques urgentes lors de brûlures chez l'enfant sont discutées dans cet article.


Assuntos
Queimaduras , Traumatismo Múltiplo , Adulto , Humanos , Criança , Serviço Hospitalar de Emergência , Hospitalização , Queimaduras/terapia
4.
Mol Psychiatry ; 26(7): 2854-2871, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33664475

RESUMO

Breastmilk contains bioactive molecules essential for brain and cognitive development. While sialylated human milk oligosaccharides (HMOs) have been implicated in phenotypic programming, their selective role and underlying mechanisms remained elusive. Here, we investigated the long-term consequences of a selective lactational deprivation of a specific sialylated HMO in mice. We capitalized on a knock-out (KO) mouse model (B6.129-St6gal1tm2Jxm/J) lacking the gene responsible for the synthesis of sialyl(alpha2,6)lactose (6'SL), one of the two sources of sialic acid (Neu5Ac) to the lactating offspring. Neu5Ac is involved in the formation of brain structures sustaining cognition. To deprive lactating offspring of 6'SL, we cross-fostered newborn wild-type (WT) pups to KO dams, which provide 6'SL-deficient milk. To test whether lactational 6'SL deprivation affects cognitive capabilities in adulthood, we assessed attention, perseveration, and memory. To detail the associated endophenotypes, we investigated hippocampal electrophysiology, plasma metabolomics, and gut microbiota composition. To investigate the underlying molecular mechanisms, we assessed gene expression (at eye-opening and in adulthood) in two brain regions mediating executive functions and memory (hippocampus and prefrontal cortex, PFC). Compared to control mice, WT offspring deprived of 6'SL during lactation exhibited consistent alterations in all cognitive functions addressed, hippocampal electrophysiology, and in pathways regulating the serotonergic system (identified through gut microbiota and plasma metabolomics). These were associated with a site- (PFC) and time-specific (eye-opening) reduced expression of genes involved in central nervous system development. Our data suggest that 6'SL in maternal milk adjusts cognitive development through a short-term upregulation of genes modulating neuronal patterning in the PFC.


Assuntos
Lactação , Leite Humano , Animais , Cognição , Feminino , Lactose , Camundongos , Oligossacarídeos
5.
Anim Cogn ; 24(5): 1109-1119, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33797625

RESUMO

Research on social cognitive ability in domestic cats is limited. The current study investigated social referencing in cats when exposed to first, a solvable, and then, an unsolvable scenario (i.e., reachable and unreachable treats) in the presence of either an attentive or an inattentive caregiver. Cats expressed more gaze alternation (P = 0.013), but less interaction with the caregiver (P = 0.048) and approached the treat container less frequently (P = 0.017) during the unsolvable test, compared to the solvable test. When in the presence of an attentive caregiver, cats initiated first gaze at the caregiver faster (P = 0.001); gazed at the caregiver for longer (P = 0.034); and approached the treat more frequently (P = 0.040), compared to when the caregiver was inattentive. Significant interaction was observed between test and caregiver's attentional state on the expression of sequential behavior, a type of showing behavior. Cats exhibited this behavior marginally more with attentive caregivers, compared to inattentive caregivers, but only during the unsolvable test. There was a decrease in sequential behavior during the unsolvable test, compared to solvable test, but this was only seen with inattentive caregivers (P = 0.018). Our results suggest that gaze alternation is a behavior reliably indicating social referencing in cats and that cats' social communication with humans is affected by the person's availability for visual interaction.


Assuntos
Atenção , Comunicação , Animais , Gatos , Cognição , Humanos , Habilidades Sociais
6.
J Paediatr Child Health ; 57(9): 1414-1419, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33847432

RESUMO

AIM: To assess different techniques to measure body composition in paediatric patients with inflammatory bowel disease using dual energy X-ray absorptiometry as a reference method. We hypothesised that a three-compartment model may demonstrate superiority over other methods as skinfold thickness equations and bioelectrical impedance analysis. METHODS: Body composition was assessed using skinfold thickness equations, bioelectrical impedance analysis and the three-compartment model. Data obtained with these methods were compared to the results obtained by dual energy X-ray absorptiometry. Statistical analysis was performed using Spearman's correlation and Bland-Altman's limits of agreement method. RESULTS: Twenty-one paediatric patients with inflammatory bowel disease were included: 11 females and 10 males; mean age for the entire group: 14.3 years, range 12-16 years. In children with inflammatory bowel disease, skinfold thickness equations, bioelectrical impedance analysis and the three-compartment model showed reliable measurements with small differences in the percentage of total body fat and good limits of agreements. CONCLUSION: The assessment of body composition using bioelectrical impedance analysis provides a valid and accurate method in children with inflammatory bowel disease as compared to dual energy X-ray absorptiometry. In the future, superiority of 3-compartment model in research and clinical settings of nutritional intervention and disease status in children with inflammatory bowel disease remains to be demonstrated.


Assuntos
Composição Corporal , Doenças Inflamatórias Intestinais , Absorciometria de Fóton , Tecido Adiposo , Adolescente , Índice de Massa Corporal , Criança , Impedância Elétrica , Feminino , Humanos , Masculino , Dobras Cutâneas
7.
Int J Food Sci Nutr ; 72(2): 236-247, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32631124

RESUMO

This study evaluated the validity of nutrient and food group intakes estimated by an FFQ against biomarkers. A 71-item semiquantitative FFQ was administered to 210 Brazilian children and adolescents aged 9-13 years. Intakes were correlated with biomarkers in plasma and red blood cells. Correlations between nutrients and their biomarkers were presented for animal protein, myristic acid (C14:0), EPA, DHA, ß-carotene, folate, and vitamins B3, B5 and B6. Food groups and biomarkers were correlated as follows: fish products with EPA and DHA; milk and dairy with C14:0, pyridoxal 5'-phosphate and vitamin B12; total vegetables and dark green and orange vegetables with ß-carotene; 5-methyltetrahydrofolate with green vegetables; and flour products with para-aminobenzoylglutamic acid. This FFQ is a valid tool for ranking Brazilian children and adolescents according to their intake of several nutrients and food groups.


Assuntos
Biomarcadores/sangue , Inquéritos sobre Dietas , Adolescente , Brasil , Criança , Feminino , Ácido Fólico/sangue , Humanos , Masculino , Inquéritos e Questionários , Vitaminas/sangue , beta Caroteno/sangue
8.
Prostate ; 80(6): 463-470, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32040869

RESUMO

BACKGROUND: In Martinique, prostate cancer (Pca) incidence rates are nowadays among the highest worldwide with a high incidence of early-onset and familial forms. Despite the demonstration of a strong familial component, identification of the genetic basis for hereditary Pca is challenging. The HOXB13 germline variant G84E (rs138213197) was described in men of European descent with Pca risk. METHODS: To investigate the potential involvement of HOXB13 mutations in Martinique, we performed sequencing of the HOXB13 coding regions of 46 index cases with early-onset Pca (before the age of 51). Additional breast cancers and controls were performed. All cancer cases analyzed in this study have been observed in the context of genetic counseling. RESULTS: We identified a rare heterozygous germline variant c.853delT (p.Ter285Lysfs) rs77179853, reported only among patients of African ancestry with a minor allele frequency of 3.2%. This variant is a stop loss reported only among patients of African ancestry with a frequency of 0.2%. CONCLUSION: In conclusion, we think that this study provides supplementary arguments that HOXB13 variants are involved in Pca.


Assuntos
Mutação em Linhagem Germinativa , Proteínas de Homeodomínio/genética , Neoplasias da Próstata/genética , Adulto , Sequência de Bases , Neoplasias da Mama/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Aconselhamento Genético , Humanos , Masculino , Martinica , Pessoa de Meia-Idade , Linhagem
9.
Prostate ; 79(14): 1640-1646, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31376218

RESUMO

BACKGROUND: There are no comparative data on pathological predictors at diagnosis, between African Caribbean and Caucasian men with prostate cancer (PCa), in equal-access centers. The objective of this study was to evaluate the grade groups of an African Caribbean cohort, newly diagnosed with PCa on prostate biopsy, compared with a Caucasian French Metropolitan cohort. METHODS: A retrospective, a comparative study was conducted between 2008 and 2016 between the University Hospital of Martinique in the French Caribbean West Indies, and the Saint Joseph Hospital in Paris. Clinical, biological, and pathological data were collected at diagnosis. The primary outcome was the grade groups for Gleason score; the secondary outcome was the PCa detection rate. Multivariate analysis was performed using linear regression. RESULTS: Of the 1880 consecutive prostate biopsy performed in the African Caribbean cohort, 945 had a diagnosis of PCa (50.3%) and 500 of 945 in the French cohort (33.8%). African Caribbean patients were older (mean 68.5 vs 67.5 years; P = .028), had worse clinical stage (13.2% vs 5.2% cT3-4; P < .001) and higher median prostate-specific antigen (PSA) level (9.23 vs 8.32 ng/mL; P = .019). On univariate analysis, African Caribbean patients had worse pathological grade groups than French patients (P < .001). Nevertheless, after adjustment on age, stage, and PSA, there were no significant differences between the two cohorts (P = .903). CONCLUSION: African Caribbean patients presented higher PCa detection rate, and higher grade groups at diagnosis than French patients in equal-access centers on univariate analysis but not on multivariate analysis. African Caribbean patients with equivalent clinical and biological characteristics than Caucasian patients at diagnosis might expect the same prognosis for PCa.


Assuntos
População Negra , Neoplasias da Próstata/patologia , Idoso , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Paris , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/química , Estudos Retrospectivos , Fatores de Risco , Regulador Transcricional ERG/análise , Índias Ocidentais , População Branca
10.
Chemistry ; 25(23): 5814-5823, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30462869

RESUMO

The synthesis of minerals should play a crucial role in the development of new and advanced materials. Since 2016, a renewal of interest to enlarge the mineral synthesis towards industrial requirements has been observed, especially thanks to three main recent papers. The innovative process exposed combines a continuous process with the use of supercritical water. In addition to curtail synthesis times, this process offers a control on the particle characteristics (size, crystallinity, structure, etc.) and a capacity to be easily transferable at an industrial scale. This innovative concept is demonstrated with the synthesis of three minerals which are the talc (a phyllomineral), the xonotlite and the tobermorite (two inominerals). This article proposes an overview of the possibilities to synthesize nanominerals in continuous processing for the development of advanced materials with promising industrial applications.

11.
Pediatr Diabetes ; 20(7): 832-841, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31254470

RESUMO

BACKGROUND: While insulin resistance (IR) is associated with specific metabolite signatures in adults, there have been few truly longitudinal studies in healthy children, either to confirm which abnormalities are present, or to determine whether they precede or result from IR. Therefore, we investigated the association of serum metabolites with IR in childhood in the Earlybird cohort. METHODS: The Earlybird cohort is a well-characterized cohort of healthy children with annual measurements from age 5 to 16 years. For the first time, longitudinal association analyses between individual serum metabolites and homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR) have been performed taking into account the effects of age, growth, puberty, adiposity, and physical activity. RESULTS: IR was higher in girls than in boys and was associated with increasing body mass index (BMI). In longitudinal analysis IR was associated with reduced concentrations of branched-chain amino acids (BCAA), 2-ketobutyrate, citrate and 3-hydroxybutyrate, and higher concentrations of lactate and alanine. These findings demonstrate the widespread biochemical consequences of IR for intermediary metabolism, ketogenesis, and pyruvate oxidation during normal child growth and development. CONCLUSIONS: Longitudinal analysis can differentiate metabolite signatures that precede or follow the development of greater levels of IR. In healthy normal weight children, higher levels of IR are associated with reduced levels of BCAA, ketogenesis, and fuel oxidation. In contrast, elevated lactate concentrations preceded the rise in IR. These changes reveal the metabolite signature of insulin action during normal growth, and they contrast with previous findings in obese children and adults that represent the consequences of IR and obesity.


Assuntos
Sangue/metabolismo , Desenvolvimento Infantil/fisiologia , Resistência à Insulina/fisiologia , Metaboloma , Adiposidade/fisiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Exercício Físico/fisiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Metabolômica/métodos , Fenótipo , Puberdade/metabolismo , Maturidade Sexual/fisiologia
12.
J Environ Manage ; 231: 1-9, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30326333

RESUMO

Competitive interactions seem to play a major role in invasive plant success. However, they have mostly been addressed through the invader impacts on other species of the plant community and rarely through the way plant communities can contain alien species. Understanding such mechanisms would help in designing restoration projects using plant community competitive properties to control invasive populations. In this study, we looked at the role of competitive interactions in the success of Fallopia japonica (Houtt.) Ronse Decraene using a native willow frequently used in bioengineering techniques: Salix viminalis L. S. viminalis has a high growth rate and is, as such, a potential candidate to compete with F. japonica in restoration projects of invaded areas. Both species were grown in semi-controlled conditions in mesocosms (truck dumpsters), alone or in competition. Morphological traits (plant height, specific leaf area) as well as biomass (aboveground and underground) were measured on each species during two growing seasons. We also quantified spatial expansion of F. japonica. Even under a dense canopy of S. viminalis, F. japonica was able to survive and grow. However, its performance was significantly reduced compared to monocultures and its spatial colonization was less extended. Although S. viminalis biomass was affected by F. japonica, F. japonica expressed competitive stress through a modification of ramet density and height. There was no significant effect of F. japonica on S. viminalis height, enabling this species to dominate. Synthesis and applications: We conclude that S. viminalis succeeded in reducing F. japonica growth by developing a competitive canopy. Bioengineering techniques aiming at restoring a competitive neighborhood can control F. japonica. However, F. japonica's broad underground extension should be taken into account in any management strategy in order to successfully limit its development and spatial spread.


Assuntos
Fallopia japonica , Polygonum , Salix , Biomassa , Folhas de Planta
13.
Gastroenterology ; 153(2): 448-459.e8, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28483500

RESUMO

BACKGROUND & AIMS: Probiotics can reduce symptoms of irritable bowel syndrome (IBS), but little is known about their effects on psychiatric comorbidities. We performed a prospective study to evaluate the effects of Bifidobacterium longum NCC3001 (BL) on anxiety and depression in patients with IBS. METHODS: We performed a randomized, double-blind, placebo-controlled study of 44 adults with IBS and diarrhea or a mixed-stool pattern (based on Rome III criteria) and mild to moderate anxiety and/or depression (based on the Hospital Anxiety and Depression scale) at McMaster University in Canada, from March 2011 to May 2014. At the screening visit, clinical history and symptoms were assessed and blood samples were collected. Patients were then randomly assigned to groups and given daily BL (n = 22) or placebo (n = 22) for 6 weeks. At weeks 0, 6, and 10, we determined patients' levels of anxiety and depression, IBS symptoms, quality of life, and somatization using validated questionnaires. At weeks 0 and 6, stool, urine and blood samples were collected, and functional magnetic resonance imaging (fMRI) test was performed. We assessed brain activation patterns, fecal microbiota, urine metabolome profiles, serum markers of inflammation, neurotransmitters, and neurotrophin levels. RESULTS: At week 6, 14 of 22 patients in the BL group had reduction in depression scores of 2 points or more on the Hospital Anxiety and Depression scale, vs 7 of 22 patients in the placebo group (P = .04). BL had no significant effect on anxiety or IBS symptoms. Patients in the BL group had a mean increase in quality of life score compared with the placebo group. The fMRI analysis showed that BL reduced responses to negative emotional stimuli in multiple brain areas, including amygdala and fronto-limbic regions, compared with placebo. The groups had similar fecal microbiota profiles, serum markers of inflammation, and levels of neurotrophins and neurotransmitters, but the BL group had reduced urine levels of methylamines and aromatic amino acids metabolites. At week 10, depression scores were reduced in patients given BL vs placebo. CONCLUSION: In a placebo-controlled trial, we found that the probiotic BL reduces depression but not anxiety scores and increases quality of life in patients with IBS. These improvements were associated with changes in brain activation patterns that indicate that this probiotic reduces limbic reactivity. ClinicalTrials.gov no. NCT01276626.


Assuntos
Bifidobacterium longum , Encéfalo/fisiopatologia , Depressão/terapia , Síndrome do Intestino Irritável/psicologia , Probióticos/administração & dosagem , Adulto , Ansiedade/fisiopatologia , Ansiedade/psicologia , Ansiedade/terapia , Encéfalo/diagnóstico por imagem , Encéfalo/microbiologia , Canadá , Depressão/fisiopatologia , Depressão/psicologia , Diarreia/microbiologia , Diarreia/terapia , Método Duplo-Cego , Emoções , Fezes/microbiologia , Feminino , Humanos , Síndrome do Intestino Irritável/fisiopatologia , Síndrome do Intestino Irritável/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento
14.
Chemistry ; 24(3): 519-542, 2018 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-28771845

RESUMO

This contribution gives a comprehensive review about the progress in preparation methods, properties and applications of the different synthetic talc types: i) crystalline nanotalc synthesized by hydrothermal treatment; ii) amorphous and/or short-range order nanotalc obtained by precipitation, and iii) organic-inorganic hybrid talc-like structures obtained through a sol-gel process or a chemical grafting. Several advantages of nanotalc such as high chemical purity, high surface area, tunable submicronic size, high thermal stability, and hydrophilic character (leading to be the first fluid mineral) are emphasized. Synthetic nanotalc applications are also considered including its use as nanofiller in composite materials, as absorbers of organic compounds, as anticorrosion coatings and as agents for cosmetic applications. Regarding their high industrial application potential, intensive research has been carried out to better understand their behavior and develop processes to produce them. To facilitate further research and development, scientific and technical challenges are discussed in this Review article.

15.
Anal Chem ; 89(10): 5565-5577, 2017 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-28437060

RESUMO

The ability to identify and quantify small molecule metabolites derived from gut microbial-mammalian cometabolism is essential for the understanding of the distinct metabolic functions of the microbiome. To date, analytical protocols that quantitatively measure a complete panel of microbial metabolites in biological samples have not been established but are urgently needed by the microbiome research community. Here, we report an automated high-throughput quantitative method using a gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) platform to simultaneously measure over one hundred microbial metabolites in human serum, urine, feces, and Escherichia coli cell samples within 15 min per sample. A reference library was developed consisting of 145 methyl and ethyl chloroformate (MCF and ECF) derivatized compounds with their mass spectral and retention index information for metabolite identification. These compounds encompass different chemical classes including fatty acids, amino acids, carboxylic acids, hydroxylic acids, and phenolic acids as well as benzoyl and phenyl derivatives, indoles, etc., that are involved in a number of important metabolic pathways. Within an optimized range of concentrations and sample volumes, most derivatives of both reference standards and endogenous metabolites in biological samples exhibited satisfactory linearity (R2 > 0.99), good intrabatch reproducibility, and acceptable stability within 6 days (RSD < 20%). This method was further validated by examination of the analytical variability of 76 paired human serum, urine, and fecal samples as well as quality control samples. Our method involved using high-throughput sample preparation, measurement with automated derivatization, and rapid GC/TOFMS analysis. Both techniques are well suited for microbiome metabolomics studies.


Assuntos
Escherichia coli/metabolismo , Formiatos/química , Ésteres do Ácido Fórmico/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metaboloma , Automação , Escherichia coli/química , Fezes/química , Humanos , Análise de Componente Principal , Reprodutibilidade dos Testes , Soro/química , Urina/química
16.
Anal Bioanal Chem ; 409(1): 295-305, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27757515

RESUMO

The methionine cycle is a key pathway contributing to the regulation of human health, with well-established involvement in cardiovascular diseases and cognitive function. Changes in one-carbon cycle metabolites have also been associated with mild cognitive decline, vascular dementia, and Alzheimer's disease. Today, there is no single analytical method to monitor both metabolites and co-factors of the methionine cycle. To address this limitation, we here report for the first time a new method for the simultaneous quantitation of 17 metabolites in the methionine cycle, which are homocysteic acid, taurine, serine, cysteine, glycine, homocysteine, riboflavin, methionine, pyridoxine, cystathionine, pyridoxamine, S-adenosylhomocysteine, S-adenosylmethionine, betaine, choline, dimethylglycine, and 5-methyltetrahydrofolic acid. This multianalyte method, developed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), provides a highly accurate and precise quantitation of these 17 metabolites for both plasma and cerebrospinal fluid metabolite monitoring. The method requires a simple sample preparation, which, combined with a short chromatographic run time, ensures a high sample throughput. This analytical strategy will thus provide a novel metabolomics approach to be employed in large-scale observational and intervention studies. We expect such a robust method to be particularly relevant for broad and deep molecular phenotyping of individuals in relation to their nutritional requirements, health monitoring, and disease risk management.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Homocisteína/sangue , Homocisteína/líquido cefalorraquidiano , Metabolômica/métodos , Metionina/sangue , Metionina/líquido cefalorraquidiano , Espectrometria de Massas em Tandem/métodos , Ensaios de Triagem em Larga Escala/métodos , Homocisteína/metabolismo , Humanos , Técnicas de Diluição do Indicador , Limite de Detecção , Redes e Vias Metabólicas , Metionina/metabolismo , Pessoa de Meia-Idade
17.
PLoS Genet ; 10(2): e1004132, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24586186

RESUMO

Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on (1)H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10(-8)) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10(-44)) and lysine (rs8101881, P = 1.2×10(-33)), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers.


Assuntos
Metaboloma/genética , Metabolômica , Polimorfismo de Nucleotídeo Único/genética , Urina , Sistemas de Transporte de Aminoácidos Básicos/genética , Animais , Doença de Crohn/genética , Doença de Crohn/metabolismo , Fucosiltransferases/genética , Fucosiltransferases/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Nefropatias/genética , Nefropatias/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Galactosídeo 2-alfa-L-Fucosiltransferase
18.
Anal Chem ; 88(15): 7617-26, 2016 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-27396289

RESUMO

Longitudinal studies aim typically at following populations of subjects over time and are important to understand the global evolution of biological processes. When it comes to longitudinal omics data, it will often depend on the overall objective of the study, and constraints imposed by the data, to define the appropriate modeling tools. Here, we report the use of multilevel simultaneous component analysis (MSCA), orthogonal projection on latent structures (OPLS), and regularized canonical correlation analysis (rCCA) to study associations between specific longitudinal urine metabonomics data and microbiome data in a diet-induced obesity model using C57BL/6 mice. (1)H NMR urine metabolic profiling was performed on samples collected weekly over a period of 13 weeks, and stool microbial composition was assessed using 16S rRNA gene sequencing at three specific time periods (baseline, first week response, end of study). MSCA and OPLS allowed us to explore longitudinal urine metabonomics data in relation to the dietary groups, as well as dietary effects on body weight. In addition, we report a data integration strategy based on regularized CCA and correlation analyses of urine metabonomics data and 16S rRNA gene sequencing data to investigate the functional relationships between metabolites and gut microbial composition. Thanks to this workflow enabling the breakdown of this data set complexity, the most relevant patterns could be extracted to further explore physiological processes at an anthropometric, cellular, and molecular level.


Assuntos
Dieta Hiperlipídica , Metabolômica , Microbiota , Animais , Bactérias/genética , Bactérias/isolamento & purificação , Peso Corporal , Fezes/microbiologia , Análise dos Mínimos Quadrados , Estudos Longitudinais , Espectroscopia de Ressonância Magnética , Masculino , Metaboloma , Camundongos , Camundongos Endogâmicos C57BL , Análise de Componente Principal , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Análise de Sequência de DNA , Urinálise
19.
Int J Mol Sci ; 17(8)2016 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-27529220

RESUMO

BACKGROUND: Growth failure and delayed puberty are well known features of children and adolescents with inflammatory bowel disease (IBD), in addition to the chronic course of the disease. Urinary metabonomics was applied in order to better understand metabolic changes between healthy and IBD children. METHODS: 21 Pediatric patients with IBD (mean age 14.8 years, 8 males) were enrolled from the Pediatric Gastroenterology Outpatient Clinic over two years. Clinical and biological data were collected at baseline, 6, and 12 months. 27 healthy children (mean age 12.9 years, 16 males) were assessed at baseline. Urine samples were collected at each visit and subjected to ¹H Nuclear Magnetic Resonance (NMR) spectroscopy. RESULTS: Using ¹H NMR metabonomics, we determined that urine metabolic profiles of IBD children differ significantly from healthy controls. Metabolic differences include central energy metabolism, amino acid, and gut microbial metabolic pathways. The analysis described that combined urinary urea and phenylacetylglutamine-two readouts of nitrogen metabolism-may be relevant to monitor metabolic status in the course of disease. CONCLUSION: Non-invasive sampling of urine followed by metabonomic profiling can elucidate and monitor the metabolic status of children in relation to disease status. Further developments of omic-approaches in pediatric research might deliver novel nutritional and metabolic hypotheses.


Assuntos
Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/urina , Adolescente , Criança , Colite Ulcerativa/metabolismo , Colite Ulcerativa/urina , Doença de Crohn/metabolismo , Doença de Crohn/urina , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Metabolômica
20.
Angew Chem Int Ed Engl ; 55(34): 9868-71, 2016 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-27321954

RESUMO

Herein we introduce a powerful and fast method to produce nanominerals using a bottom up approach. The supercritical hydrothermal flow synthesis is exploited to produce model nanominerals by mimicking natural environments at high temperatures under pressure. This innovative concept is demonstrated with the talc synthesis; this represents a major technical breakthrough since it allows decreasing the mineral-synthesis time from tens of hours to tens of seconds. Through this example, we show these nanominerals exhibit new crystal-chemistry signals and new properties. This approach provides a means to reproduce the early stages of formation of minerals in different natural environments from sedimentary environments (low temperature and pressure) to hydrothermal/metamorphic environments (high temperature and high pressure).

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