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1.
Anal Chem ; 96(2): 787-793, 2024 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-38170819

RESUMEN

In the clinic, small-molecule metabolites (SMMs) in blood are highly convincing indicators for disease diagnosis, such as cancer. However, challenges still exist for detection of SMMs due to their low concentration and complicated components in blood. In this work, we report the design of a novel "selenium signature" nanoprobe (Se nanoprobe) for efficient identification of multiple aldehyde metabolites in blood. This Se nanoprobe consists of magnetic nanoparticles that can enrich aldehyde metabolites from a complex environment, functionalized with photosensitive "selenium signature" hydrazide molecules that can react with aldehyde metabolites. Upon irradiation with UV, the aldehyde derivatives can be released from the Se nanoprobe and further sprayed by mass spectrometry through ambient ionization (AIMS). By quantifying the selenium isotope distribution (MS/MS) from the derivatization product, accurate detection of several aldehyde metabolites, including valeraldehyde (Val), heptaldehyde (Hep), 2-furaldehyde (2-Fur), 10-undecenal aldehyde (10-Und), and benzaldehyde (Ben), is realized. This strategy reveals a new solution for quick and accurate cancer diagnosis in the clinic.


Asunto(s)
Neoplasias , Selenio , Humanos , Espectrometría de Masas en Tándem/métodos , Aldehídos
2.
Metabolites ; 13(10)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37887366

RESUMEN

Epidemiological evidence regarding the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on inflammatory bowel disease (IBD) is conflicting. Additionally, little evidence exists regarding the effects of specific omega-3 components on IBD risk. We applied two-sample Mendelian randomization (MR) to disentangle the effects of omega-3 PUFAs (including total omega-3, α-linolenic acid, eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA)) on the risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Our findings indicated that genetically predicted increased EPA concentrations were associated with decreased risk of IBD (odds ratio 0.78 (95% CI 0.63-0.98)). This effect was found to be mediated through lower levels of linoleic acid and histidine metabolites. However, we found limited evidence to support the effects of total omega-3, α-linolenic acid, and DHA on the risks of IBD. In the fatty acid desaturase 2 (FADS2) region, robust colocalization evidence was observed, suggesting the primary role of the FADS2 gene in mediating the effects of omega-3 PUFAs on IBD. Therefore, the present MR study highlights EPA as the predominant active component of omega-3 fatty acids in relation to decreased risk of IBD, potentially via its interaction with linoleic acid and histidine metabolites. Additionally, the FADS2 gene likely mediates the effects of omega-3 PUFAs on IBD risk.

3.
J Transl Med ; 21(1): 370, 2023 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-37286992

RESUMEN

BACKGROUND: Observational studies and conventional Mendelian randomization (MR) studies showed inconclusive evidence to support the association between omega-3 fatty acids and type 2 diabetes. We aim to evaluate the causal effect of omega-3 fatty acids on type 2 diabetes mellitus (T2DM), and the distinct intermediate phenotypes linking the two. METHODS: Two-sample MR was performed using genetic instruments derived from a recent genome-wide association study (GWAS) of omega-3 fatty acids (N = 114,999) from UK Biobank and outcome data obtained from a large-scale T2DM GWAS (62,892 cases and 596,424 controls) in European ancestry. MR-Clust was applied to determine clustered genetic instruments of omega-3 fatty acids that influences T2DM. Two-step MR analysis was used to identify potential intermediate phenotypes (e.g. glycemic traits) that linking omega-3 fatty acids with T2DM. RESULTS: Univariate MR showed heterogenous effect of omega-3 fatty acids on T2DM. At least two pleiotropic effects between omega-3 fatty acids and T2DM were identified using MR-Clust. For cluster 1 with seven instruments, increasing omega-3 fatty acids reduced T2DM risk (OR: 0.52, 95%CI 0.45-0.59), and decreased HOMA-IR (ß = - 0.13, SE = 0.05, P = 0.02). On the contrary, MR analysis using 10 instruments in cluster 2 showed that increasing omega-3 fatty acids increased T2DM risk (OR:1.10; 95%CI 1.06-1.15), and decreased HOMA-B (ß = - 0.04, SE = 0.01, P = 4.52 × 10-5). Two-step MR indicated that increasing omega-3 fatty acid levels decreased T2DM risk via decreasing HOMA-IR in cluster 1, while increased T2DM risk via decreasing HOMA-B in cluster 2. CONCLUSIONS: This study provides evidence to support two distinct pleiotropic effects of omega-3 fatty acids on T2DM risk influenced by different gene clusters, which could be partially explained by distinct effects of omega-3 fatty acids on insulin resistance and beta cell dysfunction. The pleiotropic feature of omega-3 fatty acids variants and its complex relationships with T2DM need to be carefully considered in future genetic and clinical studies.


Asunto(s)
Diabetes Mellitus Tipo 2 , Ácidos Grasos Omega-3 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Análisis de la Aleatorización Mendeliana , Estudio de Asociación del Genoma Completo , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Fenotipo , Polimorfismo de Nucleótido Simple/genética
4.
Front Endocrinol (Lausanne) ; 14: 1124479, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37152926

RESUMEN

Background: Idiopathic hyperaldosteronism (IHA) is one of the most common types of primary aldosteronism (PA), an important cause of hypertension. Although high dietary sodium is a major risk factor for hypertension, there is no consensus on the recommended dietary sodium intake for IHA. Objective: This study investigated the effect of a low-sodium diet on hemodynamic variables and relevant disease biomarkers in IHA patients, with the aim of providing a useful reference for clinical treatment. Methods: Fifty IHA patients were evenly randomized into two groups and provided, after a 7-day run-in period (100 mmol/d sodium), either a low-sodium diet (50 mmol/d sodium) or a normal sodium diet (100 mmol/d sodium) for an additional 7 days. After the 14-day intervention (conducted without potassium supplementation), changes in blood pressure (BP) and serum potassium were evaluated in both groups. Results: After the dietary intervention, the low sodium group exhibited, compared to the normal sodium group, decreased BP (SBP: 121.8 ± 12.8 vs. 129.9 ± 12.1 mmHg, p < 0.05; DBP: 82.6 ± 7.6 vs. 86.4 ± 8.2 mmHg, p < 0.05; MAP: 95.7 ± 8.8 vs. 100.9 ± 8.4 mmHg, p < 0.05) and increased serum potassium levels (3.38 ± 0.33 vs. 3.07 ± 0.27 mmol/L, p < 0.001). The low sodium group showed also better control of both BP and serum potassium: BP <140/90 mmHg in 70.0% of total patients (76.0% vs. 64.0%, in the low and normal sodium groups, respectively; p > 0.05), BP <130/85 mmHg in 38.0% of total patients (56.0% vs. 20.0%, p < 0.05), BP <120/80 mmHg in 28.0% of total patients (44.0% vs. 12.0%, p < 0.05); serum potassium ≥3.5 mmol/L in 22.0% of total patients (32.0% vs. 12.0% in the low and normal sodium groups, respectively; p = 0.088). There were differences between the controlled BP group (<120/80 mmHg) and the non-controlled BP group (≥120/80 mmHg) in gender, BP at baseline, and type of diet (low vs. normal sodium). Female gender and low-sodium diet were protective factors for BP control. Conclusions: A low-sodium diet is effective in lowering BP and elevating serum potassium in IHA patients. Female patients on a low-sodium diet are more likely to achieve BP control (<120/80 mmHg). We advocate a dietary sodium intake of 50 mmol/d for IHA patients. Clinical trial registration: https://clinicaltrials.gov, Identifier NCT05649631.


Asunto(s)
Hiperaldosteronismo , Hipertensión , Sodio en la Dieta , Humanos , Femenino , Dieta Hiposódica , Hipertensión/etiología , Hipertensión/tratamiento farmacológico , Sodio , Sodio en la Dieta/uso terapéutico , Potasio , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/tratamiento farmacológico
5.
Chin J Nat Med ; 21(4): 308-320, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37120249

RESUMEN

Viscum coloratum (Kom.) Nakai is a well-known medicinal plant. However, the optimal harvest time for V. coloratum is unknown. Few studies were performed to analyze compound variation during storage and to improve post-harvest quality control. Our study aimed to comprehensively evaluate the quality of V. coloratum in different growth stages, and determine the dynamic variation of metabolites. Ultra-performance liquid chromatography tandem mass spectrometry was used to quantify 29 compounds in V. coloratum harvested in six growth periods, and the associated biosynthetic pathways were explored. The accumulation of different types of compounds were analyzed based on their synthesis pathways. Grey relational analysis was used to evaluate the quality of V. coloratum across different months. The compound variation during storage was analyzed by a high-temperature high-humidity accelerated test. The results showed that the quality of V. coloratum was the hightest in March, followed by November, and became the lowest in July. During storage, compounds in downstream steps of the biosynthesis pathway were first degraded to produce the upstream compounds and some low-molecular-weight organic acids, leading to an increase followed by a decrease in the content of some compounds, and resulted in a large gap during the degradation time course among different compounds. Due to the rapid rate and large degree of degradation, five compounds were tentatively designated as "early warning components" for quality control. This report provides reference for better understanding the biosynthesis and degradation of metabolites in V. coloratum and lays a theoretical foundation for rational application of V. coloratum and better quality control of V. coloratum during storage.


Asunto(s)
Plantas Medicinales , Viscum , Viscum/química , Plantas Medicinales/química , Cromatografía Liquida , Espectrometría de Masas , Metabolómica
6.
J Pharm Anal ; 12(2): 243-252, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35582400

RESUMEN

Viscum coloratum (Kom.) Nakai is a well-known medicinal hemiparasite widely distributed in Asia. The synthesis and accumulation of its metabolites are affected by both environmental factors and the host plants, while the latter of which is usually overlooked. The purpose of this study was to comprehensively evaluate the effects of host and habitat on the metabolites in V. coloratum through multiple chemical and biological approaches. The metabolite profile of V. coloratum harvested from three different host plants in two habitats were determined by multiple chemical methods including high-performance liquid chromatography-ultraviolet (HPLC-UV), gas chromatography-flame ionization detector (GC-FID) and ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF/MS). The differences in antioxidant efficacy of V. coloratum were determined based on multiple in vitro models. The multivariate statistical analysis and data fusion strategy were applied to analyze the differences in metabolite profile and antioxidant activity of V. coloratum. Results indicated that the metabolite profile obtained by various chemical approaches was simultaneously affected by host and environment factors, and the environment plays a key role. Meanwhile, three main differential metabolites between two environment groups were identified. The results of antioxidant assay indicated that the environment has greater effects on the biological activity of V. coloratum than the host. Therefore, we conclude that the integration of various chemical and biological approaches combined with multivariate statistical and data fusion analysis, which can determine the influences of host plant and habitat on the metabolites, is a powerful strategy to control the quality of semi-parasitic herbal medicine.

7.
Gut Microbes ; 14(1): 2003176, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34923903

RESUMEN

Non-fasting lipidemia (nFL), mainly contributed by postprandial lipidemia (PL), has recently been recognized as an important cardiovascular disease (CVD) risk as fasting lipidemia (FL). PL serves as a common feature of dyslipidemia in Type 2 Diabetes (T2D), albeit effective therapies targeting on PL were limited. In this study, we aimed to evaluate whether the therapy combining probiotics (Prob) and berberine (BBR), a proven antidiabetic and hypolipidemic regimen via altering gut microbiome, could effectively reduce PL in T2D and to explore the underlying mechanism. Blood PL (120 min after taking 100 g standard carbohydrate meal) was examined in 365 participants with T2D from the Probiotics and BBR on the Efficacy and Change of Gut Microbiota in Patients with Newly Diagnosed Type 2 Diabetes (PREMOTE study), a random, placebo-controlled, and multicenter clinical trial. Prob+BBR was superior to BBR or Prob alone in improving postprandial total cholesterol (pTC) and low-density lipoprotein cholesterol (pLDLc) levels with decrement of multiple species of postprandial lipidomic metabolites after 3 months follow-up. This effect was linked to the changes of fecal Bifidobacterium breve level responding to BBR alone or Prob+BBR treatment. Four fadD genes encoding long-chain acyl-CoA synthetase were identified in the genome of this B. breve strain, and transcriptionally activated by BBR. In vitro BBR treatment further decreased the concentration of FFA in the culture medium of B. breve compared to vehicle. Thus, the activation of fadD by BBR could enhance FFA import and mobilization in B. breve and diliminish the intraluminal lipids for absorption to mediate the effect of Prob+BBR on PL. Our study confirmed that BBR and Prob (B. breve) could exert a synergistic hypolipidemic effect on PL, acting as a gut lipid sink to achieve better lipidemia and CVD risk control in T2D.


Asunto(s)
Berberina/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hiperlipidemias/tratamiento farmacológico , Probióticos/administración & dosificación , Adulto , Animales , Colesterol/sangre , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/microbiología , Método Doble Ciego , Quimioterapia Combinada , Heces/microbiología , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/microbiología , Masculino , Persona de Mediana Edad , Periodo Posprandial/efectos de los fármacos
8.
Nat Commun ; 12(1): 7080, 2021 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-34873153

RESUMEN

Males are generally more susceptible to impaired glucose metabolism and type 2 diabetes (T2D) than females. However, the underlying mechanisms remain to be determined. Here, we revealed that gut microbiome depletion abolished sexual dimorphism in glucose metabolism. The transfer of male donor microbiota into antibiotics-treated female mice led the recipients to be more insulin resistant. Depleting androgen via castration changed the gut microbiome of male mice to be more similar to that of females and improved glucose metabolism, while reintroducing dihydrotestosterone (DHT) reversed these alterations. More importantly, the effects of androgen on glucose metabolism were largely abolished when the gut microbiome was depleted. Next, we demonstrated that androgen modulated circulating glutamine and glutamine/glutamate (Gln/Glu) ratio partially depending on the gut microbiome, and glutamine supplementation increases insulin sensitivity in vitro. Our study identifies the effects of androgen in deteriorating glucose homeostasis partially by modulating the gut microbiome and circulating glutamine and Gln/Glu ratio, thereby contributing to the difference in glucose metabolism between the two sexes.


Asunto(s)
Andrógenos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Glucosa/metabolismo , Homeostasis/efectos de los fármacos , Células 3T3-L1 , Animales , Antibacterianos/farmacología , Línea Celular , Dihidrotestosterona/farmacología , Trasplante de Microbiota Fecal , Femenino , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiología , Ácido Glutámico/sangre , Glutamina/sangre , Células Hep G2 , Humanos , Resistencia a la Insulina/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Orquiectomía , Factores Sexuales
9.
J Clin Endocrinol Metab ; 106(9): e3619-e3633, 2021 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-33950216

RESUMEN

CONTEXT: Vertical sleeve gastrectomy (VSG) is becoming a prioritized surgical intervention for obese individuals; however, the brain circuits that mediate its effective control of food intake and predict surgical outcome remain largely unclear. OBJECTIVE: We investigated VSG-correlated alterations of the gut-brain axis. METHODS: In this observational cohort study, 80 patients with obesity were screened. A total of 36 patients together with 26 normal-weight subjects were enrolled and evaluated using the 21-item Three-Factor Eating Questionnaire (TFEQ), MRI scanning, plasma intestinal hormone analysis, and fecal sample sequencing. Thirty-two patients underwent VSG treatment and 19 subjects completed an average of 4-month follow-up evaluation. Data-driven regional homogeneity (ReHo) coupled with seed-based connectivity analysis were used to quantify VSG-related brain activity. Longitudinal alterations of body weight, eating behavior, brain activity, gastrointestinal hormones, and gut microbiota were detected and subjected to repeated measures correlation analysis. RESULTS: VSG induced significant functional changes in the right putamen (PUT.R) and left supplementary motor area, both of which correlated with weight loss and TFEQ scores. Moreover, postprandial levels of active glucagon-like peptide-1 (aGLP-1) and Ghrelin were associated with ReHo of PUT.R; meanwhile, relative abundance of Clostridia increased by VSG was associated with improvements in aGLP-1 secretion, PUT.R activity, and weight loss. Importantly, VSG normalized excessive functional connectivities with PUT.R, among which baseline connectivity between PUT.R and right orbitofrontal cortex was related to postoperative weight loss. CONCLUSION: VSG causes correlated alterations of gut-brain axis, including Clostridia, postprandial aGLP-1, PUT.R activity, and eating habits. Preoperative connectivity of PUT.R may represent a potential predictive marker of surgical outcome in patients with obesity.


Asunto(s)
Encéfalo/fisiopatología , Gastrectomía/métodos , Hormonas Gastrointestinales/sangre , Microbioma Gastrointestinal , Obesidad/metabolismo , Obesidad/cirugía , Adulto , Peso Corporal , Corteza Cerebral/fisiopatología , Estudios de Cohortes , Ingestión de Alimentos , Femenino , Ghrelina/sangre , Péptido 1 Similar al Glucagón/sangre , Humanos , Imagen por Resonancia Magnética , Masculino , Corteza Motora/fisiopatología , Obesidad/microbiología , Putamen/fisiopatología , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto Joven
10.
Anal Chem ; 93(3): 1749-1756, 2021 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-33351590

RESUMEN

Significant efforts have been made to develop robust and reliable methods for simultaneous biothiols determination in different matrices, but there still exist the problems such as easy oxidation, tedious derivatization, and difficulty in discrimination, which brings unsatisfactory results in their accuracy and fast quantification in biological samples. To overcome these problems, a simultaneous biothiols detection method combining a "selenium signature" chemical probe and paper spray mass spectrometry (PS-MS) was proposed. In the strategy, the modified-paper substrate is used to enhance the analytical performance. Chemical probe Ebselen-NH2 that has a specific response to biothiols was designed and covalently fixed on the surface of an oxidized paper substrate. By the identification of derivatized product with distinctive selenium isotope distribution and employment of the optimized PS-MS method, qualitative and quantitative analysis of five biothiols including glutathione (GSH), cysteine (Cys), cysteinylglycine (CysGly), N-acetylcysteine (Nac), and homocysteine (Hcy) were realized. Biothiols in plasma and cell lysates were measured with satisfactory results. The established method not only provides a novel protocol for simultaneous determination of biothiols, but also is helpful for understanding the biological and clinical roles played by these bioactive small molecules.


Asunto(s)
Acetilcisteína/análisis , Cisteína/análisis , Dipéptidos/análisis , Colorantes Fluorescentes/química , Glutatión/análisis , Papel , Selenio/química , Técnicas Biosensibles , Cisteína/análogos & derivados , Humanos , Espectrometría de Masas
11.
Nat Commun ; 11(1): 5015, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-33024120

RESUMEN

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).


Asunto(s)
Berberina/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Probióticos/uso terapéutico , Berberina/uso terapéutico , Femenino , Microbioma Gastrointestinal/fisiología , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Masculino , Metagenoma/efectos de los fármacos , Metagenoma/genética , Persona de Mediana Edad , Placebos , Resultado del Tratamiento
12.
Metabolism ; 112: 154353, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32916152

RESUMEN

BACKGROUND: The transcription factor YY1 is an important regulator for metabolic homeostasis. Activating mutations in YY1 lead to tumorigenesis of pancreatic ß-cells, however, the physiological functions of YY1 in ß-cells are still unknown. Here, we investigated the effects of YY1 ablation on insulin secretion and glucose metabolism. METHODS: We established two models of ß-cell-specific YY1 knockout mice. The glucose metabolic phenotypes, ß-cell mass and ß-cell functions were analyzed in the mouse models. Transmission electron microscopy was used to detect the ultrastructure of ß-cells. The flow cytometry analysis, measurement of OCR and ROS were performed to investigate the mitochondrial function. Histological analysis, quantitative PCR and ChIP were performed to analyze the target genes of YY1 in ß-cells. RESULTS: Our results showed that loss of YY1 resulted in reduction of insulin production, ß-cell mass and glucose tolerance in mice. Ablation of YY1 led to defective ATP production and mitochondrial ROS accumulation in pancreatic ß-cells. The inactivation of YY1 impaired the activity of mitochondrial oxidative phosphorylation, induced mitochondrial dysfunction and diabetes in mouse models. CONCLUSION: Our findings demonstrate that the transcriptional activity of YY1 is essential for the maintenance of mitochondrial functions and insulin secretion in ß-cells.


Asunto(s)
Diabetes Mellitus/metabolismo , Resistencia a la Insulina/genética , Secreción de Insulina/genética , Células Secretoras de Insulina/metabolismo , Mitocondrias/metabolismo , Factor de Transcripción YY1/genética , Animales , Diabetes Mellitus/genética , Modelos Animales de Enfermedad , Glucosa/metabolismo , Ratones , Ratones Noqueados , Mitocondrias/genética , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo
13.
J Genet ; 992020.
Artículo en Inglés | MEDLINE | ID: mdl-32089530

RESUMEN

The endangered medicinal plant Glehnia littoralis is one of the important natural source of furanocoumarin, which has been used as mucolytic, antitussive, antitumour and antibacterial. However, the genetic information of furanocoumarin biosynthesis in G. littoralis is scarce at present. The objective of this study was to mine the putative candidate genes involved in the biosynthesis pathwayof furanocoumarin and provide references for gene identification, and functional genomics of G. littoralis. We carried out the transcriptome analysis of leaves and roots in G. littoralis, which provided a dataset for gene mining. Psoralen, imperatorin and isoimperatorin were detected in G. littoralis by high performance liquid chromatography analysis. Candidate key genes were mined based on the annotations and local BLAST with homologous sequences using BioEdit software. The relative expression of genes was analysed using quantitative real-time polymerase chain reaction. Further, the CYP450 genes were mined using phylogenetic analyses using MEGA 6.0 software. Atotal of 156,949 unigenes were generated, of which 9021 were differentially-expressed between leaves and roots. A total of 82 unigenes encoding eight enzymes in furanocoumarin biosynthetic pathway were first obtained. Seven genes that encoded key enzymes in the downstream furanocoumarin biosynthetic pathway and expressed more in roots than leaves were screened. Twenty-six candidate CYP450 unigenes expressed abundantly in roots and were chiefly concentrated in CYP71, CYP85 and CYP72 clans. Finally, we filtered 102 differentially expressed transcription factors (TFs) unigenes. The transcriptome of G. littoralis was characterized which would help to elucidate the furanocoumarin biosynthetic pathway in G. littoralis and provide an invaluable resource for further study of furanocoumarin.


Asunto(s)
Apiaceae/genética , Apiaceae/metabolismo , Vías Biosintéticas/genética , Furocumarinas/biosíntesis , Perfilación de la Expresión Génica , Plantas Medicinales/genética , Plantas Medicinales/metabolismo , Apiaceae/clasificación , Biología Computacional/métodos , Regulación de la Expresión Génica de las Plantas , Anotación de Secuencia Molecular , Filogenia , Plantas Medicinales/clasificación , Transcriptoma
14.
Diabetes ; 69(1): 48-59, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31649162

RESUMEN

Statins are cholesterol-lowering agents that increase the incidence of diabetes and impair glucose tolerance via their detrimental effects on nonhepatic tissues, such as pancreatic islets, but the underlying mechanism has not been determined. In atorvastatin (ator)-treated high-fat diet-fed mice, we found reduced pancreatic ß-cell size and ß-cell mass, fewer mature insulin granules, and reduced insulin secretion and glucose tolerance. Transcriptome profiling of primary pancreatic islets showed that ator inhibited the expression of pancreatic transcription factor, mechanistic target of rapamycin (mTOR) signaling, and small G protein (sGP) genes. Supplementation of the mevalonate pathway intermediate geranylgeranyl pyrophosphate (GGPP), which is produced by 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, significantly restored the attenuated mTOR activity, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) expression, and ß-cell function after ator, lovastatin, rosuvastatin, and fluvastatin treatment; this effect was potentially mediated by sGP prenylation. Rab5a, the sGP in pancreatic islets most affected by ator treatment, was found to positively regulate mTOR signaling and ß-cell function. Rab5a knockdown mimicked the effect of ator treatment on ß-cells. Thus, ator impairs ß-cell function by regulating sGPs, for example, Rab5a, which subsequently attenuates islet mTOR signaling and reduces functional ß-cell mass. GGPP supplementation could constitute a new approach for preventing statin-induced hyperglycemia.


Asunto(s)
Atorvastatina/farmacología , Células Secretoras de Insulina/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Ácido Mevalónico/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Recuento de Células , Células Cultivadas , Femenino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Células Secretoras de Insulina/citología , Células Secretoras de Insulina/fisiología , Islotes Pancreáticos/crecimiento & desarrollo , Masculino , Redes y Vías Metabólicas/genética , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos/genética , Fosfatos de Poliisoprenilo/farmacología , Transducción de Señal/genética
15.
J Photochem Photobiol B ; 194: 188-193, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31004866

RESUMEN

Theranostic agents were drawing a huge attention in the personalized medication. In this study, we established a facile technique, plant extract-based technique for the synthesis of reduced nano-graphene oxide (RNGO) with low cytotoxicity. We formed platforms of photothermal (PT) therapy and further explained that the synthesized RNGO can be utilized as ready to use PT therapy without any additional surface adjustment. In the meantime, with the help of a constant-wave NIR laser (near-infrared), in vitro esophageal adenocarcinoma cell line (OE-19) cancer cells were effectively ablated, because of the PT impact of RNGO. The outcomes propose that the RNGO was appropriate for PT therapy and photoacoustic imaging of the tumor, which is assuring for theranostic nanomedicine.


Asunto(s)
Absorción de Radiación , Neoplasias Esofágicas/terapia , Grafito/química , Grafito/farmacología , Rayos Infrarrojos , Óxidos/química , Fototerapia/métodos , Línea Celular Tumoral , Neoplasias Esofágicas/patología , Grafito/uso terapéutico , Humanos , Oxidación-Reducción
16.
Biomed Res Int ; 2018: 7928241, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30410939

RESUMEN

BACKGROUND: Inflammatory myofibroblastic tumor (IMT), as a mesenchymal tumor, is common in the lung and abdomen but rare in the paranasal sinus and nasopharynx. OBJECTIVE: This study aimed to summarize the clinical characteristics of IMT in the paranasal sinus and nasopharynx and analyze the relationship between the treatment and the overall survival (OS). METHOD: The clinical features, treatment, and follow-up data of patients diagnosed with IMT of the paranasal sinus or nasopharynx from 2006 to 2017 were retrospectively analyzed, and the previous literature was reviewed. RESULTS: IMT often presents as an ill-defined soft-tissue mass with bone destruction and invasion of surrounding structures. The treatment methods used in this study were different combinations of surgery, prednisone, radiotherapy, and chemotherapy or observation alone. Three of the 13 patients were lost and the follow-up time of the remaining 10 cases ranged from 2 to 87 months (median, 39 months). Two patients died of the disease; the other eight patients were stable. The 5-year survival rate was 72%. Among the four methods of treatment, only treatment with prednisone was significantly correlated with better OS (P = 0.046). CONCLUSIONS: IMT is an intermediate tumor that often mimics malignancy. We are not sure if IMTs in the nasal cavity are more aggressive because of the biology or if the location and local therapy in the head region is more complicated. Radiologic findings help know the extent of the lesion. For unresectable nasal IMT, combined therapy with glucocorticoids, chemotherapy, and radiotherapy is sometimes a better choice. Glucocorticoids are especially recommended as a basic part of the integrated therapy. However, the standard treatment needs further research.


Asunto(s)
Neoplasias de Tejido Muscular/patología , Neoplasias de los Senos Paranasales/patología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cavidad Nasal/patología , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Adulto Joven
17.
J Environ Radioact ; 181: 138-146, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29150188

RESUMEN

The influences of N species and transpiration on the Fe plaque (IP) formation and related aquatic U rhizofiltration had not revealed yet, especially when these factors were co-existed. It was evaluated in a mesocosm experiment in the condition of respective ammonium (NH4+)/nitrate (NO3-) cultivation of Phragmites australis Trin ex Steud. coupled with different transpiration rates (TRs). The results suggested that the enhanced transpiration of P. australis improved the aquatic U rhizofiltration in both NO3- and NH4+ rich milieus. However, the NO3- dependent oxidizing milieu restricted aquatic U uptake by the root of P. australis (up to 47.6 ± 1.8 mg kg-1 under high TR) via IP assisted rhizofiltration. The high aquatic U availability and limited IP formation in NO3- rich milieu benefited the U retention within root tissue. On the contrary, the aquatic U rhizofiltration (up to 62.1 ± 1.0 mg kg-1 under high TR) was enhanced under NH4+ dependent reductive milieu. It was mainly contributed by U retention within IP. The area related U accumulation in different N species cultured roots was enhanced but did not significantly different under higher TR condition. The result suggested that the supplied NH4+ coupled with enhanced transpiration was supposed to be more optimized option for IP assisted aquatic U rhizofiltration via P. australis.


Asunto(s)
Nitrógeno/metabolismo , Poaceae/fisiología , Uranio/metabolismo , Contaminantes Radiactivos del Agua/metabolismo , Biodegradación Ambiental , Transporte Biológico , Hierro/química , Raíces de Plantas/metabolismo , Rizoma , Contaminantes Radiactivos del Agua/análisis , Humedales
18.
Nat Commun ; 8(1): 1785, 2017 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-29176714

RESUMEN

Antidiabetic medication may modulate the gut microbiota and thereby alter plasma and faecal bile acid (BA) composition, which may improve metabolic health. Here we show that treatment with Acarbose, but not Glipizide, increases the ratio between primary BAs and secondary BAs and plasma levels of unconjugated BAs in treatment-naive type 2 diabetes (T2D) patients, which may beneficially affect metabolism. Acarbose increases the relative abundances of Lactobacillus and Bifidobacterium in the gut microbiota and depletes Bacteroides, thereby changing the relative abundance of microbial genes involved in BA metabolism. Treatment outcomes of Acarbose are dependent on gut microbiota compositions prior to treatment. Compared to patients with a gut microbiota dominated by Prevotella, those with a high abundance of Bacteroides exhibit more changes in plasma BAs and greater improvement in metabolic parameters after Acarbose treatment. Our work highlights the potential for stratification of T2D patients based on their gut microbiota prior to treatment.


Asunto(s)
Acarbosa/uso terapéutico , Ácidos y Sales Biliares/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Bacteroides/fisiología , Bifidobacterium/fisiología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiología , Heces/química , Femenino , Glipizida/uso terapéutico , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Humanos , Lactobacillus/fisiología , Masculino , Persona de Mediana Edad , Dinámica Poblacional
19.
Mol Nutr Food Res ; 61(9)2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28500724

RESUMEN

SCOPE: Obesity and associated metabolic complications is a worldwide public health issue. Gut microbiota have been recently linked to obesity and its related inflammation. In this study, we have explored the anti-inflammatory effect of grape seed proanthocyanindin extract (GSPE) in the high-fat diet (HFD)-induced obesity and identified the contribution of the gut microbiota to GSPE effects on metabolism. METHODS AND RESULTS: Mice were fed a normal diet and a high-fat diet with or without GSPE (300 mg/kg body weight/day) by oral gavage for 7 weeks. Supplementation with GSPE significantly decreased plasma levels of inflammatory factors such as TNF-α, IL-6 and MCP-1, companied with ameliorated macrophage infiltration in epidydimal fat and liver tissues. Furthermore, GSPE also reduced epidydimal fat mass and improved insulin sensitivity. 16S rDNA analyses revealed that GSPE supplementation modulated the gut microbiota composition and certain bacteria including Clostridium XIVa, Roseburia and Prevotella. More importantly, depleting gut microbiota by antibiotics treatment abolished the beneficial effects of GSPE on inflammation and adiposity. CONCLUSION: Our study identifies the novel links between gut microbiota alterations and metabolic benefits by GSPE supplementation, providing possibilities for the prevention and treatment of metabolic disorders by targeting gut microbiota through a potential prebiotic agent GSPE.


Asunto(s)
Adiposidad/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Extracto de Semillas de Uva/farmacología , Inflamación/tratamiento farmacológico , Proantocianidinas/farmacología , Animales , Dieta Alta en Grasa , Interleucina-6/sangre , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/sangre
20.
Environ Sci Pollut Res Int ; 24(13): 12185-12194, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28353101

RESUMEN

Studies have revealed that the rhizofiltration is a feasible plant-based technology for aquatic metal/metalloid removal. However, the performance of aquatic U retention via rhizofiltration has not been fully revealed yet. In this study, a field investigation was conducted in a Phragmites australis Trin ex Steud. dominated wetland to estimate the efficiency of Fe plaque (IP)-assisted U rhizofiltration, with redox-state gradient (-179 to 220 mV) and low aquatic U level (66.7 to 92.0 µg l-1). The U concentrations were determined in soil, root, and aboveground biomass of P. australis. The IP on root surface was extracted via DCB extraction procedure. The bio-concentration factor (BCF) was applied to evaluate the aquatic U transfer capacity from root to above ground biomass of P. australis. The result suggested that root of P. australis was highly effective for aquatic U uptake via rhizofiltration (BCF 1025 to 1556). It also benefited the real U accumulation in aboveground biomass of P. australis (up to 0.4 mg m-2) and related plant-water-soil U recycling. The IP and associated microbial community in rhizosphere was effective mediator for aquatic U retention on root surface (BCF 1162 to 847). The IP-assisted aquatic U rhizofiltration was significantly promoted in relatively reductive environment. It was benefited by the enhanced root uptake of Fe due to lower oxidizers (e.g., DO and NO3-) availability. On the other hand, the competitive adsorption effect from co-existing IP-affinitive elements (e.g., As) also possibly impaired the real capacity of IP-assisted aquatic U rhizofiltration via P. australis.


Asunto(s)
Uranio , Humedales , Poaceae , Rizosfera , Suelo
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