Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 102
Filtrar
1.
Front Vet Sci ; 8: 706987, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660756

RESUMO

Fecal microbiota transplantation (FMT) documented transplanting a donor fecal sample to a receipt individual for a desired physiologic effect. However, whether the gut microbiota construction, intestinal maturation, and behavioral plasticity are modulated by FMT during the early life of broilers is waiting for verification. To evaluate the role of transfer of fecal microbiota from aged broilers donor (BD) to another individual, 96 birds were equally divided into a check (CK, control) group and a broiler recipient (BR) group. FMT was conducted daily from 5 to 12 days of age to determine the future impact on body weight, behavior, intestinal development, and gut microbiota. Results indicated that fearfulness in the CK group was higher than the BR group in both the behavioral tests (p < 0.05). The muscularis mucosa, thickness of muscle layer, and thickness of serous membrane layer in the BR group were higher compared with those of the CK group in the jejunum (p < 0.05). In the gut microbiota, Shannon diversity showed no difference, while beta diversity presented a difference in principal coordination analysis (PCoA) between the CK and BR groups. At the phylum level, the relative abundance of Lentisphaerae in the CK group was lower than the BR (p = 0.052) and BD (p = 0.054) groups. The relative abundance of Tenericutes in the BD group was higher than that in the CK and BR groups (p < 0.05). At the genus level, Megamonas in the CK group was higher than the BR (p = 0.06) and BD (p < 0.05) groups. In the BR group, the functional capabilities of microbial communities analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were increased in the glutamatergic synapse and N-glycan biosynthesis pathways in comparison with the CK and BD groups (p < 0.05). Some characteristics of gut microbiota in the donor chickens could be transferred to recipient chickens by FMT. In conclusion, exogenous FMT as a probiotic-like administration might be an efficient way to improve the physiology and behavior of chickens. Notably, the role of microbiota for various individuals and periods remains undefined, and the mechanism of microbiota on behaviors still needs further investigation.

2.
Obesity (Silver Spring) ; 29(10): 1708-1718, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34490739

RESUMO

OBJECTIVE: A Mendelian randomization (MR) framework was applied to disentangle the causal effect of branched-chain amino acids (BCAAs) and overweight/obesity in Chinese adolescents. METHODS: Circulating BCAA levels were measured by liquid chromatography coupled with mass spectrometry. A total of 7 BCAAs and 12 BMI-associated common variants identified from released genome-wide association study results were genotyped. Furthermore, a bidirectional MR approach was undertaken to disentangle the causal effect of BCAAs and overweight/obesity, using two-stage regression. RESULTS: Using the inverse variance-weighted strategy and the weighted genetic scoring instruments, the estimated odds ratio per 1-arbitrary-unit increase in the total BCAA level on overweight and obesity odds after adjusting for age and sex was 2.40 (95% CI: 1.38 to 3.42, p < 0.001) and 2.55 (95% CI: 1.35 to 4.82, p = 0.004), respectively. Furthermore, additional MR tests were undertaken using a reversed model, testing the causal effect of increasing BMI variants on total BCAA level. By contrast, no evidence that increased BMI was causally associated with the total BCAA level (estimated ß associated with 1-kg/m2 increase in BMI = 0.05, 95% CI: -0.17 to 0.28, p = 0.642) was observed. CONCLUSIONS: In summary, BCAAs may be causally associated with overweight/obesity or, rather, a congenital dysmetabolism of BCAAs could be a cause of overweight/obesity in adolescents.

3.
J Pharm Biomed Anal ; 205: 114288, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34371449

RESUMO

Prostate cancer (PCa) is associated with cellular metabolism alterations leading to changes of the metabolome. So far, studies investigating these alterations mainly focused on comparisons of metabolite profiles of PCa patients and healthy controls. In the present study we compared for the first time metabolite profiles in a significant number of paired urine samples collected before and eight weeks after radical prostatectomy (rPX) in 34 patients with PCa. Our comprehensive non-targeted liquid chromatographic-mass spectrometric metabolomics approach covered > 3000 metabolite ion masses. We annotated 23 metabolites showing significant changes eight weeks after rPX. While the levels of uridine and six acylcarnitines in urine were increased before surgery, lower levels were detected for 16 metabolites, like e.g. citrate, phenyl-lactic acid, choline, myo-inositol, emphasizing a relevant pathophysiological role of these biomarkers and the associated metabolic pathways. These results have important implications for potential use of metabolome analyses for detection of prostate cancer and related pathologic and molecular features.


Assuntos
Metaboloma , Neoplasias da Próstata , Humanos , Masculino , Metabolômica , Prostatectomia , Neoplasias da Próstata/cirurgia
4.
Se Pu ; 39(3): 281-290, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-34227309

RESUMO

Respiratory syncytial virus (RSV) can cause lower respiratory tract infections, such as bronchiolitis in infants. In China, traditional asthma-relieving medicine has numerous clinical applications in the treatment of RSV infections. However, due to the complexity of the traditional Chinese medicine system, its therapeutic mechanism and main pharmacological components remain unclear. Metabolomics can be used to analyze the efficacy of traditional Chinese medicine to provide modern scientific evidence for such treatments. In this study, an animal model experiment was performed with seven groups of three-week-old rats. The model group and five intervention groups were inoculated nasally with RSV for three consecutive days, and the normal group was treated with the same amount of saline for three consecutive days under the same conditions. In parallel, the five intervention groups were treated separately with the following via intragastric administration for seven consecutive days: asthma-relieving traditional Chinese medicine decoction, its three constituent agents (ascending (xuan) therapy, descending (jiang) therapy, pyretic clearing (qing) therapy), and ribavirin. Both normal group and RSV model group were administered with normal saline via intragastric administration as controls for seven consecutive days. The fundus plasma of rats in each group was collected on day 0, day 3, and day 7. Liquid chromatography-mass spectrometry-based untargeted metabolomics analysis was performed to investigate the changes in the metabolome after RSV infection, the effects of the asthma-relieving decoction on the regulation of metabolites related to RSV infection, and the primary source of efficacy. The detected metabolite ions were corrected using internal standards. Multivariate analysis of ions with an RSD value of less than 30% in quality control (QC) samples was used to construct principal component analysis models to monitor the overall metabolic changes of each group. The results showed that, during RSV infection and treatment, the asthma-relieving decoction and the positive control ribavirin had similar effects on the overall metabolic regulation of RSV-infected rats. Among the three asthma-relieving decoction constituent agents, the ascending (xuan) therapy agents which was composed of ephedra and ginkgo had a closer metabolic regulation effect with asthma-relieving decoction, and might be the main source of pharmacological efficacy. Based on the retention time, m/z value and tandem mass spectra in the database established by our laboratory, a total of 150 metabolites were identified. Paired t-tests were performed using data of the identified metabolites before and after RSV infection in each group, and it was found that 83 metabolite levels significantly changed after RSV infection, indicating that RSV infection could lead to disorders of multiple metabolic pathways in rats. The altered pathways included aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, primary bile acid biosynthesis, phenylalanine metabolism and sphingomyelin metabolism. On the third day, the asthma-relieving decoction had regulatory effects on several metabolites such as bile acids, amino acids, organic acids, lipids, etc. Among the three asthma-relieving decoction constituent agents, the ascending (xuan) therapy agents had more similar effects on the regulation of metabolites with the asthma-relieving decoction. On the other hand, the descending (jiang) therapy agents and pyretic clearing (qing) therapy agents down-regulated the abnormal increase in acylcarnitine caused by the RSV infection. Additionally, both asthma-relieving decoction and its constituent agents could maintain the stability of the immune system and metabolism of the intestinal flora in rats. This study used metabolomics to evaluate the efficacy of an asthma-relieving decoction and demonstrate the metabolites and the corresponding changes after asthma-relieving decoction-based treatment. It provides theoretical support for research on the therapeutic mechanism and active ingredients of asthma-relieving decoction.


Assuntos
Asma , Medicamentos de Ervas Chinesas , Metabolômica , Infecções por Vírus Respiratório Sincicial , Animais , Asma/tratamento farmacológico , China , Cromatografia Líquida , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Espectrometria de Massas , Medicina Tradicional Chinesa , Ratos , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico
5.
Anal Chem ; 93(31): 10916-10924, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34328315

RESUMO

From microbes to human beings, nontargeted metabolic profiling by liquid chromatography (LC)-mass spectrometry (MS) has been commonly used to investigate metabolic alterations. Still, a major challenge is the annotation of metabolites from thousands of detected features. The aim of our research was to go beyond coverage of metabolite annotation in common nontargeted metabolomics studies by an integrated multistep strategy applying data-dependent acquisition (DDA)-based ultrahigh-performance liquid chromatography (UHPLC)-high-resolution mass spectrometry (HRMS) analysis followed by comprehensive neutral loss matches for characteristic metabolite modifications and database searches in a successive manner. Using pooled human urine as a model sample for method establishment, we found 22% of the detected compounds having modifying structures. Major types of metabolite modifications in urine were glucuronidation (33%), sulfation (20%), and acetylation (6%). Among the 383 annotated metabolites, 100 were confirmed by standard compounds and 50 modified metabolites not present in common databases such as human metabolite database (HMDB) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were structurally elucidated. Practicability was tested by the investigation of urines from pregnant women diagnosed with gestational diabetes mellitus vs healthy controls. Overall, 83 differential metabolites were annotated and 67% of them were modified metabolites including five previously unreported compounds. To conclude, the systematic modifying group-assisted strategy can be taken as a useful tool to extend the number of annotated metabolites in biological and biomedical nontargeted studies.


Assuntos
Metabolômica , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Bases de Dados Factuais , Feminino , Humanos , Espectrometria de Massas , Gravidez
6.
J Chromatogr A ; 1651: 462271, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34102397

RESUMO

Successful applications of lipidomics in clinic need study large-scale samples, and the bottlenecks are in throughput and robustness of the lipid analytical method. Here, we report an untargeted lipidomics method by combining high throughput pretreatment in the 96-well plate with ultra-high performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry. The developed method was validated to have satisfactory analytical characteristics in terms of linearity, repeatability and extraction recovery. It can be used to handle 96 samples simultaneously in 25 min and detect 441 lipids in plasma sample. Storage stability investigation on lipid extracts provided an operable procedure for large-scale sample analysis and demonstrated most lipids were stable in autosampler at 10 °C within 36 h and at -80 °C within 72 h after the pretreatment. To prove the usefulness, the method was employed to investigate abnormal plasma lipidome related to atrial fibrillation. A biomarker panel with the area under the curve (AUC) values of 0.831 and 0.745 was achieved in the discovery and external validation sets, respectively. These results showed that the developed method is applicable for large-scale biological sample handling and lipid analysis of plasma.


Assuntos
Fibrilação Atrial/metabolismo , Lipidômica/métodos , Cromatografia Líquida de Alta Pressão , Análise Discriminante , Feminino , Humanos , Análise dos Mínimos Quadrados , Limite de Detecção , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
7.
Molecules ; 26(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34069043

RESUMO

Cherries are rich in bioactive phenolic compounds and are often fermented into cherry wines. The degradation of anthocyanins during storage will cause color deterioration. The study aimed to utilize sinapic acid and grape tannins in cherry wine to maintain a high fraction in the colored forms of anthocyanins, in order to maximize the color intensity, the latter being associated with good product quality. The effects on the anthocyanin profile and on color parameters of copigments, utilizing spectral measurement combined with UPLC-MS quantitative analysis, have been evaluated in sweet cherry wines. The copigmentation effect of sinapic acid and grape tannin was accompanied by the bathochromic shift and the hyperchromic effect, which lead to an increase in color intensity (lower L*, higher a* and b*). During the aging process, sinapic and grape tannin increased the content of pyranoanthocyanins in cherry wine, especially the addition of sinapic acid makes the cherry wine generate 10-syringyl-pyranocyanidin-3-rutinoside. These results demonstrate that sinapic acid is suitable for adding before alcohol fermentation, while grape tannins can be added before aging.


Assuntos
Antocianinas/análise , Ácidos Cumáricos/análise , Prunus avium/química , Taninos/análise , Vinho/análise , Antocianinas/química , Cor , Ácidos Cumáricos/química , Pigmentação , Análise de Componente Principal , Proantocianidinas/análise , Proantocianidinas/química , Espectrofotometria Ultravioleta , Taninos/química
8.
Front Endocrinol (Lausanne) ; 12: 659268, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149613

RESUMO

Background: Polycystic ovary syndrome (PCOS) is a complex reproductive endocrine disorder. And metabolic syndrome (MS) is an important bridge for PCOS patients to develop other diseases, such as diabetes and coronary heart disease. Our aim was to study the potential metabolic characteristics of PCOS-MS and identify sensitive biomarkers so as to provide targets for clinical screening, diagnosis, and treatment. Methods: In this study, 44 PCOS patients with MS, 34 PCOS patients without MS, and 32 healthy controls were studied. Plasma samples of subjects were tested by ultraperformance liquid chromatography (UPLC) system combined with LTQ-orbi-trap mass spectrometry. The changes of metabolic characteristics from PCOS to PCOS-MS were systematically analyzed. Correlations between differential metabolites and clinical characteristics of PCOS-MS were assessed. Differential metabolites with high correlation were further evaluated by the receiver operating characteristic (ROC) curve to identify their sensitivity as screening indicators. Results: There were significant differences in general characteristics, reproductive hormone, and metabolic parameters in the PCOS-MS group when compared with the PCOS group and healthy controls. We found 40 differential metabolites which were involved in 23 pathways when compared with the PCOS group. The metabolic network further reflected the metabolic environment, including the interaction between metabolic pathways, modules, enzymes, reactions, and metabolites. In the correlation analysis, there were 11 differential metabolites whose correlation coefficient with clinical parameters was greater than 0.4, which were expected to be taken as biomarkers for clinical diagnosis. Besides, these 11 differential metabolites were assessed by ROC, and the areas under curve (AUCs) were all greater than 0.7, with a good sensitivity. Furthermore, combinational metabolic biomarkers, such as glutamic acid + leucine + phenylalanine and carnitine C 4: 0 + carnitine C18:1 + carnitine C5:0 were expected to be sensitive combinational biomarkers in clinical practice. Conclusion: Our study provides a new insight to understand the pathogenesis mechanism, and the discriminating metabolites may help screen high-risk of MS in patients with PCOS and provide sensitive biomarkers for clinical diagnosis.

9.
Opt Express ; 29(7): 10265-10274, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33820166

RESUMO

Manipulation of femtosecond laser induced microstructures in glass by tuning the laser polarization has great potential in optics. Here we report two different polarization-dependent microstructures and their evolution with pulse repetition rate in an aluminosilicate glass induced by femtosecond laser irradiation. A V-shaped crack oriented parallel to the laser polarization plane is induced at the bottom of modified regions by pulses operated at 200 kHz, 1030 nm, and 300 fs. Further increasing the pulse repetition rate to 500 kHz leads to the formation of a dumbbell-shaped structure, which is elongated perpendicularly to the laser polarization, at the top of the modified region. The size of the coloration area and the dumbbell-shaped structure can be controlled by tuning the pulse duration. Further investigation indicates that higher numerical apertures are in favor of the presence of the polarization effects in femtosecond laser irradiation. The possible mechanism responsible for the formation of the two microstructures is discussed. These results could be helpful for understanding of ultrafast laser interaction with glass.

10.
Glob Chall ; 5(4): 2000088, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33854788

RESUMO

In a Chinese prospective cohort, 500 patients with new-onset type 2 diabetes (T2D) within 4.61 years and 500 matched healthy participants are selected as case and control groups, and randomized into discovery and validation sets to discover the metabolite changes before T2D onset and the related diabetogenic loci. A serum metabolomics analysis reveals that 81 metabolites changed significantly before T2D onset. Based on binary logistic regression, eight metabolites are defined as a biomarker panel for T2D prediction. Pipecolinic acid, carnitine C14:0, epinephrine and phosphatidylethanolamine 34:2 are first found associated with future T2D. The addition of the biomarker panel to the clinical markers (BMI, triglycerides, and fasting glucose) significantly improves the predictive ability in the discovery and validation sets, respectively. By associating metabolomics with genomics, a significant correlation (p < 5.0 × 10-8) between eicosatetraenoic acid and the FADS1 (rs174559) gene is observed, and suggestive correlations (p < 5.0 × 10-6) between pipecolinic acid and CHRM3 (rs535514), and leucine/isoleucine and WWOX (rs72487966) are discovered. Elevated leucine/isoleucine levels increased the risk of T2D. In conclusion, multiple metabolic dysregulations are observed to occur before T2D onset, and the new biomarker panel can help to predict T2D risk.

11.
Foods ; 10(4)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918556

RESUMO

Traditional food allergen identification mainly relies on in vivo and in vitro experiments, which often needs a long period and high cost. The artificial intelligence (AI)-driven rapid food allergen identification method has solved the above mentioned some drawbacks and is becoming an efficient auxiliary tool. Aiming to overcome the limitations of lower accuracy of traditional machine learning models in predicting the allergenicity of food proteins, this work proposed to introduce deep learning model-transformer with self-attention mechanism, ensemble learning models (representative as Light Gradient Boosting Machine (LightGBM) eXtreme Gradient Boosting (XGBoost)) to solve the problem. In order to highlight the superiority of the proposed novel method, the study also selected various commonly used machine learning models as the baseline classifiers. The results of 5-fold cross-validation showed that the area under the receiver operating characteristic curve (AUC) of the deep model was the highest (0.9578), which was better than the ensemble learning and baseline algorithms. But the deep model need to be pre-trained, and the training time is the longest. By comparing the characteristics of the transformer model and boosting models, it can be analyzed that, each model has its own advantage, which provides novel clues and inspiration for the rapid prediction of food allergens in the future.

12.
Diabetes Care ; 44(2): 499-510, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33355246

RESUMO

OBJECTIVE: Comprehensive assessment of serum bile acids (BAs) aberrations before diabetes onset remains inconclusive. We examined the association of serum BA profile and coregulation with the risk of developing type 2 diabetes mellitus (T2DM) among normoglycemic Chinese adults. RESEARCH DESIGN AND METHODS: We tested 23 serum BA species in subjects with incident diabetes (n = 1,707) and control subjects (n = 1,707) matched by propensity score (including age, sex, BMI, and fasting glucose) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study, which was composed of 54,807 normoglycemic Chinese adults with a median follow-up of 3.03 years. Multivariable-adjusted odds ratios (ORs) for associations of BAs with T2DM were estimated using conditional logistic regression. RESULTS: In multivariable-adjusted logistic regression analysis, per SD increment of unconjugated primary and secondary BAs were inversely associated with incident diabetes, with an OR (95% CI) of 0.89 (0.83-0.96) for cholic acid, 0.90 (0.84-0.97) for chenodeoxycholic acid, and 0.90 (0.83-0.96) for deoxycholic acid (P < 0.05 and false discovery rate <0.05). On the other hand, conjugated primary BAs (glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, and sulfated glycochenodeoxycholic acid) and secondary BA (tauroursodeoxycholic acid) were positively related with incident diabetes, with ORs ranging from 1.11 to 1.19 (95% CIs ranging between 1.05 and 1.28). In a fully adjusted model additionally adjusted for liver enzymes, HDL cholesterol, diet, 2-h postload glucose, HOMA-insulin resistance, and waist circumference, the risk estimates were similar. Differential correlation network analysis revealed that perturbations in intraclass (i.e., primary and secondary) and interclass (i.e., unconjugated and conjugated) BA coregulation preexisted before diabetes onset. CONCLUSIONS: These findings reveal novel changes in BAs exist before incident T2DM and support a potential role of BA metabolism in the pathogenesis of diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Adulto , Ácidos e Sais Biliares , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Jejum , Humanos , Pessoa de Meia-Idade
13.
J Proteome Res ; 20(1): 1005-1014, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33347754

RESUMO

Large-scale population screenings are not feasible by applying laborious oral glucose tolerance tests, but using fasting blood glucose (FPG) and glycated hemoglobin (HbA1c), a considerable number of diagnoses are missed. A novel marker is urgently needed to improve the diagnostic accuracy of broad-scale diabetes screening in easy-to-collect blood samples. In this study, by applying a novel knowledge-based, multistage discovery and validation strategy, we scaled down from 108 diabetes-associated metabolites to a diagnostic metabolite triplet (Met-T), namely hexose, 2-hydroxybutyric/2-hydroxyisobutyric acid, and phenylalanine. Met-T showed in two independent cohorts, each comprising healthy controls, prediabetic, and diabetic individuals, distinctly higher diagnostic sensitivities for diabetes screening than FPG alone (>79.6 vs <68%). Missed diagnoses decreased from >32% using fasting plasma glucose down to <20.4%. Combining Met-T and fasting plasma glucose further improved the diagnostic accuracy. Additionally, a positive association of Met-T with future diabetes risk was found (odds ratio: 1.41; p = 1.03 × 10-6). The results reveal that missed prediabetes and diabetes diagnoses can be markedly reduced by applying Met-T alone or in combination with FPG and it opens perspectives for higher diagnostic accuracy in broad-scale diabetes-screening approaches using easy to collect sample materials.


Assuntos
Diabetes Mellitus , Estado Pré-Diabético , Glicemia , Diabetes Mellitus/diagnóstico , Jejum , Teste de Tolerância a Glucose , Hemoglobina A Glicada/análise , Humanos , Estado Pré-Diabético/diagnóstico
14.
Metabolites ; 10(12)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255474

RESUMO

Gliomas are the most aggressive phenotypes of brain tumors and are classified into four grades according to the malignancy degree by the World Health Organization. Metabolic profiling can provide an overview of metabolic reprogramming at a specific stage of tumor initiation and development. Studies about metabolic alterations related to different grades of gliomas are helpful to understand the molecular mechanism for progression of glioma. In the current study, metabolomics and lipidomics analyses based on chromatography-mass spectrometry were performed on different grades of glioma tissues. Differential metabolites between glioma and para-tumor tissues were studied and used as the basis to explore metabolic alterations related to glioma grading. It was found that short-chain acylcarnitines were elevated, whereas lysophosphatidylethanolamines (LPEs) were decreased in high-grade gliomas. Furthermore, the gene expression of short/branched-chain acyl-coenzyme dehydrogenase (ACADSB), which is involved in fatty acid oxidation, was found down-regulated with glioma progression by analyzing related genes and pathways. In addition, LPE metabolism showed a significant difference among different grades of gliomas. These important metabolic pathways related to glioma progression may provide potential clues for further study on the mechanisms and treatment of glioma.

15.
Front Plant Sci ; 11: 564385, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33281839

RESUMO

Grape (Vitis vinifera L.) is a fruit tree with high salt tolerance and high nutritional value, medicinal value, and economic value. Suberin in roots is characterized by long-chain fatty acids and is thought to be related to the salt tolerance of grape. The key enzyme in the fatty acid elongation process is ß-ketoacyl-CoA synthase (KCS). The function and the regulatory mechanism of VvKCS in response to salt stress in grape are unclear. In this study, VvKCS was isolated from V. vinifera L. A real-time quantitative polymerase chain reaction analysis showed that salt stress enhanced VvKCS transcription levels in grapes. Overexpression of VvKCS increased the tolerance to salt stress in Arabidopsis during the germination and seedling stages. The improved salt tolerance was the result of the combined contributions of multiple mechanisms including the regulation of expression of ion transporters and channels, accumulation of osmotic regulating substances, and maintenance of membrane stability. The results of this study are valuable information on plant salt tolerance and provide a theoretical basis for the molecular mechanism of grape salt tolerance.

16.
Anal Chim Acta ; 1139: 8-14, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33190713

RESUMO

In metabolomics study, it is not easy to extract the metabolites from data of ultra high-performance liquid chromatography-high-resolution mass spectrometry, especially for those with low abundance. Different software for peak recognition and matching use different algorithms, leading to different extract results. Therefore, integration of results from different software can obtain richer metabolome information, but the redundant features should be removed. In this study, an integrated strategy of fusing features and removing redundancy based on graph density (FRRGD) was proposed. A graph is used to cover the ion features generated by two open access software (XCMS, MZmine 2) and a software (SIEVE) from an instrument vendor, and redundant features were removed by searching the maximal complete sub-graphs. A standard mixture containing 41 metabolites and a spontaneous urine were utilized to develop the method and demonstrate its usefulness. For the standard mixture, 19, 19 and 27 metabolites were extracted by XCMS, MZmine 2 and SIEVE, respectively. After fusion by FRRGD, 37 metabolites were obtained. For the diluted spontaneous urine sample, 1103, 1500 and 387 metabolites were extracted by XCMS, MZmine 2 and SIEVE, respectively, FRRGD produced 1619 metabolites which were much more than individual software, significantly increasing metabolome coverage. The proposed FRRGD shows a great prospect as a new data processing strategy for metabolomics study.


Assuntos
Metabolômica , Software , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Metaboloma
17.
Adv Sci (Weinh) ; 7(22): 2001714, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33240754

RESUMO

Diabetic retinopathy (DR) is the main cause of vision loss or blindness in working age adults worldwide. The lack of effective diagnostic biomarkers for DR leads to unsatisfactory curative treatments. To define potential metabolite biomarkers for DR diagnosis, a multiplatform-based metabolomics study is performed. In this study, a total of 905 subjects with diabetes without DR (NDR) and with DR at different clinical stages are recruited. Multiplatform metabolomics methods are used to characterize the serum metabolic profiles and to screen and validate the DR biomarkers. Based on the criteria p < 0.05 and false-discovery rate < 0.05, 348 and 290 metabolites are significantly associated with the pathogenesis of DR and early-stage DR, respectively. The biomarker panel consisting of 12-hydroxyeicosatetraenoic acid (12-HETE) and 2-piperidone exhibited better diagnostic performance than hemoglobin A1c (HbA1c) in differentiating DR from diabetes, with AUCs of 0.946 versus 0.691 and 0.928 versus 0.648 in the discovery and validation sets, respectively. In addition, this panel showed higher sensitivity in early-stage DR detection than HbA1c. In conclusion, this multiplatform-based metabolomics study comprehensively revealed the metabolic dysregulation associated with DR onset and progression. The defined biomarker panel can be used for detection of DR and early-stage DR.

18.
Nat Commun ; 11(1): 5015, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024120

RESUMO

Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], -1.04[-1.19, -0.89]%) and BBR-alone group (-0.99[-1.16, -0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (-0.59[-0.75, -0.44]%, -0.53[-0.68, -0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).


Assuntos
Berberina/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/uso terapêutico , Berberina/uso terapêutico , Feminino , Microbioma Gastrointestinal/fisiologia , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Masculino , Metagenoma/efeitos dos fármacos , Metagenoma/genética , Pessoa de Meia-Idade , Placebos , Resultado do Tratamento
19.
Cancers (Basel) ; 12(7)2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32640711

RESUMO

Despite it being the most common incident of cancer among men, the pathophysiological mechanisms contributing to prostate cancer (PCa) are still poorly understood. Altered mitochondrial metabolism is postulated to play a role in the development of PCa. To determine the key metabolites (which included mitochondrial oncometabolites), benign prostatic and cancer tissues of patients with PCa were analyzed using capillary electrophoresis and liquid chromatography coupled with mass spectrometry. Gene expression was studied using real-time PCR. In PCa tissues, we found reduced levels of early tricarboxylic acid cycle metabolites, whereas the contents of urea cycle metabolites including aspartate, argininosuccinate, arginine, proline, and the oncometabolite fumarate were higher than that in benign controls. Fumarate content correlated positively with the gene expression of oncogenic HIF1α and NFκB pathways, which were significantly higher in the PCa samples than in the benign controls. Furthermore, data from the TCGA database demonstrated that prostate cancer patients with activated NFκB pathway had a lower survival rate. In summary, our data showed that fumarate content was positively associated with carcinogenic genes.

20.
Plant J ; 104(1): 171-184, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32634860

RESUMO

Leaf senescence represents the final stage of leaf growth and development, and its onset and progression are strictly regulated; however, the underlying regulatory mechanisms remain largely unknown. In this study we found that WRKY42 was highly induced during leaf senescence. Loss-of-function wrky42 mutants showed delayed leaf senescence whereas the overexpression of WRKY42 accelerated senescence. Transcriptome analysis revealed 2721 differentially expressed genes between wild-type and WRKY42-overexpressing plants, including genes involved in salicylic acid (SA) and reactive oxygen species (ROS) synthesis as well as several senescence-associated genes (SAGs). Moreover, WRKY42 activated the transcription of isochorismate synthase 1 (ICS1), respiratory burst oxidase homolog F (RbohF) and a few SAG genes. Consistently, the expression of these genes was reduced in wrky42 mutants but was markedly increased in transgenic Arabidopsis overexpressing WRKY42. Both in vitro electrophoretic mobility shift assays (EMSAs) and in vivo chromatin immunoprecipitation and dual luciferase assays demonstrated that WRKY42 directly bound to the promoters of ICS1 and RbohF, as well as a few SAGs, to activate their expression. Genetic analysis further showed that mutations of ICS1 and RbohF suppressed the early senescence phenotype evoked by WRKY42 overexpression. Thus, we have identified WRKY42 as a novel transcription factor positively regulating leaf senescence by directly activating the transcription of ICS1, RbohF and SAGs, without any seed yield penalty.


Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácido Salicílico/metabolismo , Fatores de Transcrição/fisiologia , Envelhecimento/genética , Envelhecimento/metabolismo , Arabidopsis/fisiologia , Proteínas de Arabidopsis/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas/fisiologia , Folhas de Planta/fisiologia , Fatores de Transcrição/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...