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1.
Opt Express ; 29(6): 7986-7997, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33820254

RESUMEN

In this work, quasi-static mode degradation in high power fiber amplifiers has been investigated experimentally. An increase of M2 from 1.3 to 2.6 with distortion of the beam profile is observed, which results in the signal spectra and backward light characterization departing from the traditional phenomena. The amplifier has been operated at the same input pump power of 705 W for nearly 2.2 hours to investigate the relationship between quasi-static mode degradation and photodarkening. The evolution of M2 factor/beam profile, mode correlation coefficient and output laser power at different working times indicate that the quasi-static mode degradation in the high power fiber amplifiers is dependent on photodarkening and evolves on the scale of tens of minutes. A visible green light has been injected to photobleach the gain fiber for 19 hours, which reveals that the quasi-static mode degradation has been suppressed simultaneously. To the best of our knowledge, this is the first detail report of photodarkening-induced quasi-static degradation in high power fiber amplifiers.

2.
Appl Opt ; 60(24): 7346-7350, 2021 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-34613022

RESUMEN

Five-hundred-watt cylindrical vector beams (CVBs) at 1030 nm with the 3 dB linewidth being less than 0.25 nm have been generated from a narrow linewidth all-fiber linearly polarized laser by metasurface extracavity conversion. At maximum output power, the transmission efficiency and polarization extinction ratio of radially polarized cylindrical vector beams (RP-CVBs) are beyond 98% and 95%, respectively. The average power is approximately an order higher than previously reported high-power narrow-linewidth CVBs generated from fiber lasers. The temperature rise of the metasurface is less than 10°C at 500 W output power, which means that the system can be further power-scaled in the near future. The high-power, high-purity, and high-efficiency RP-CVBs generated by the metasurface demonstrate potential application of a metasurface in high-power CVBs lasers.

3.
Crit Rev Biotechnol ; 39(4): 524-540, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30810398

RESUMEN

Diabetes mellitus (DM) increases the risk of cardiovascular diseases and other secondary complications, such as nephropathy, neuropathy, retinopathy, etc. The important risk factors for the pathogenesis of DM are aging, family history, sedentary lifestyle, unhealthy dietary habits, and obesity. Evidence from epidemiological studies also indicates that DM is characterized by specific alterations in the human gut microbiota (GM). GM transplantation in rodents and humans revealed that a specific GM constituent can be the cause and not just the consequence of the DM condition and complications. These findings suggest a potential role of GM in human health, disease prevention, and treatment. Dietary intervention studies using dietary fibers (DFs) suggested that modulation of the GM can suppress the metabolic risk markers in humans. However, a causal role of GM in such studies remains unexplored. Long-term follow-up studies disclosed that the diet rich in insoluble and non-viscous fibers are responsible for DF-mediated antidiabetic activities, while soluble and viscous fibers have little influence on DM despite having a profound impact on glycemia. However, general conclusions cannot be drawn simply based on these findings. Long-term follow-up studies are urgently required in this area to explore the therapeutic potential of different DFs in treating DM and to delineate the exact role of GM involvement. Here we review and discuss the signature of GM during DM, antidiabetic activity of metformin via GM modulation, DFs from different sources and their antidiabetic activity, and the possible role of GM involvement.


Asunto(s)
Diabetes Mellitus/dietoterapia , Dieta , Fibras de la Dieta/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Glucemia/efectos de los fármacos , Diabetes Mellitus/microbiología , Humanos
4.
Appl Opt ; 56(10): 2661-2666, 2017 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-28375226

RESUMEN

A fiber laser injection system used as a seeder for a high-power laser facility of inertial confinement fusion was designed to meet stringent requirements. Herein, we demonstrate the fiber laser injection system, whose output single-pulse energy reaches the millijoule class. With two-stage amplitude modulators, the system produces a pulse with a higher pulse shaping capability. In addition, amplifying the pulse with large-mode-area fiber and single polarization, large-mode-area photonic crystal fiber (PCF) ensures a good beam quality output. In this proof-of-principle experiment, the long-term stability of FM-to-AM modulation and pulse energy is demonstrated. The successful demonstration of this laser injection system holds great significance for future high-power laser drivers.

5.
Food Res Int ; 175: 113794, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38129067

RESUMEN

Cell cultured meat is a novel and promising technology, but developing specific culture medium for muscle cells remains one of the main technical obstacles. FGF1 signaling is reported to promote proliferation and maintain proliferative capacity of satellite cells. However, the effect of FGF1 as a supplement to serum-free medium on satellite cells in vitro culture is still unclear. In this study, an efficient method for the production of soluble and biologically active recombinant bovine FGF1 (rbFGF1) protein in Escherichia coli was established. The soluble expression level of TrxA-rbFGF1 fusion protein was 562 mg/L in shake flasks, resulting in 5.5 mg of pure rbFGF1 from 0.1 L of starting culture. In serum-free culture conditions, rbFGF1 effectively promoted the proliferation and regulated the mitochondrial morphology and function of C2C12 myoblasts.rbFGF1 activated extracellular signal-regulated kinases1/2 (ERK1/2) signaling in C2C12 myoblasts, which further stimulated dynamin related protein 1 (DRP1) Ser616 phosphorylation. These findings highlighted the potential application of rbFGF1 in developing effective serum-free medium for cultured meat production.


Asunto(s)
Factor 1 de Crecimiento de Fibroblastos , Células Satélite del Músculo Esquelético , Animales , Bovinos , Factor 1 de Crecimiento de Fibroblastos/farmacología , Dinámicas Mitocondriales/fisiología , Fosforilación , Proliferación Celular
6.
J Agric Food Chem ; 72(27): 15190-15197, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38807430

RESUMEN

Cultured meat technology is expected to solve problems such as resource shortages and environmental pollution, but the muscle fiber differentiation efficiency of cultured meat is low. Genipin is the active compound derived from Gardenia jasminoides Ellis, which has a variety of activities. Additionally, genipin serves as a noncytotoxic agent for cross-linking, which is suitable as a foundational scaffold for in vitro tissue regeneration. However, the impact of genipin on myoblast differentiation remains to be studied. The research revealed that genipin was found to improve the differentiation efficiency of myoblasts. Genipin improved mitochondrial membrane potential by activating the AMPK signaling pathway of myoblasts, promoting mitochondrial biogenesis, and mitochondrial network remodeling. Genipin activated autophagy in myoblasts and maintained cellular homeostasis. Autophagy inhibitors blocked the pro-differentiation effect of genipin. These results showed that genipin improved the differentiation efficiency of myoblasts, which provided a theoretical basis for the development of cultured meat technology.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Autofagia , Diferenciación Celular , Iridoides , Mioblastos , Transducción de Señal , Iridoides/farmacología , Iridoides/química , Diferenciación Celular/efectos de los fármacos , Mioblastos/efectos de los fármacos , Mioblastos/citología , Mioblastos/metabolismo , Autofagia/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Animales , Ratones , Transducción de Señal/efectos de los fármacos , Línea Celular , Humanos
7.
Food Funct ; 15(13): 6929-6942, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38659316

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is a worldwide public health issue, but a widely accepted therapy is still lacking until now. Anthocyanins are natural flavonoid compounds that possess various bioactivities, but their applications are limited due to their low bioavailability and stability. Acylated anthocyanins are reported to show higher stability, whereas their effects on NAFLD are still unclear. Herein, pelargonidin-3-O-(6''-acetyl)-glucoside (Ace Pg3G) was found to dose-dependently reduce intracellular lipid droplets and triglycerides, and improve cellular oxidative stress that accompanied lipid deposition. Besides, Ace Pg3G was proved to activate AMPK phosphorylation, thus stimulating AMPK-mediated lysosome-autophagy pathway to eliminate overloaded lipid. Further study unveiled that Ace Pg3G regulated genes related to lipid metabolism downstream of AMPK to inhibit lipid synthesis and accelerate lipid oxidation. Overall, this study provided the first evidence, to our best knowledge, that Ace Pg3G ameliorated free fatty acid-induced lipid deposition in hepatocytes through regulating AMPK-mediated autophagy pathways and redox state.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Antocianinas , Autofagia , Hepatocitos , Metabolismo de los Lípidos , Lisosomas , Oxidación-Reducción , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Autofagia/efectos de los fármacos , Antocianinas/farmacología , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Glucósidos/farmacología , Células Hep G2 , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Animales , Estrés Oxidativo/efectos de los fármacos , Ratones
8.
Elife ; 132024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235443

RESUMEN

Noncoding RNA plays a pivotal role as novel regulators of endothelial cell function. Type 2 diabetes, acknowledged as a primary contributor to cardiovascular diseases, plays a vital role in vascular endothelial cell dysfunction due to induced abnormalities of glucolipid metabolism and oxidative stress. In this study, aberrant expression levels of circHMGCS1 and MIR4521 were observed in diabetes-induced human umbilical vein endothelial cell dysfunction. Persistent inhibition of MIR4521 accelerated development and exacerbated vascular endothelial dysfunction in diabetic mice. Mechanistically, circHMGCS1 upregulated arginase 1 by sponging MIR4521, leading to decrease in vascular nitric oxide secretion and inhibition of endothelial nitric oxide synthase activity, and an increase in the expression of adhesion molecules and generation of cellular reactive oxygen species, reduced vasodilation and accelerated the impairment of vascular endothelial function. Collectively, these findings illuminate the physiological role and interacting mechanisms of circHMGCS1 and MIR4521 in diabetes-induced cardiovascular diseases, suggesting that modulating the expression of circHMGCS1 and MIR4521 could serve as a potential strategy to prevent diabetes-associated cardiovascular diseases. Furthermore, our findings provide a novel technical avenue for unraveling ncRNAs regulatory roles of ncRNAs in diabetes and its associated complications.


Asunto(s)
Diabetes Mellitus Tipo 2 , Endotelio Vascular , Hidroximetilglutaril-CoA Sintasa , MicroARNs , ARN Circular , Animales , Humanos , Masculino , Ratones , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Ratones Endogámicos C57BL , MicroARNs/metabolismo , MicroARNs/genética , ARN Circular/genética , ARN Circular/metabolismo , Hidroximetilglutaril-CoA Sintasa/genética
9.
J Mol Biol ; : 168737, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39102976

RESUMEN

The study of protein-protein interactions (PPIs) holds immense significance in understanding various biological activities, as well as in drug discovery and disease diagnosis. Existing deep learning methods for PPI prediction, including graph neural networks (GNNs), have been widely employed as the solutions, while they often experience a decline in performance in the real world. We claim that the topological shortcut is one of the key problems contributing negatively to the performance, according to our analysis. By modeling the PPIs as a graph with protein as nodes and interactions as edge types, the prevailing models tend to learn the pattern of nodes' degrees rather than intrinsic sequence-structure profiles, leading to the problem termed topological shortcut. The huge data growth of PPI leads to intensive computational costs and challenges computing devices, causing infeasibility in practice. To address the discussed problems, we propose a label-aware hierarchical subgraph learning method (laruGL-PPI) that can effectively infer PPIs while being interpretable. Specifically, we introduced edge-based subgraph sampling to effectively alleviate the problems of topological shortcuts and high computing costs. Besides, the inner-outer connections of PPIs are modeled as a hierarchical graph, together with the dependencies between interaction types constructed by a label graph. Extensive experiments conducted across various scales of PPI datasets have conclusively demonstrated that the laruGL-PPI method surpasses the most advanced PPI prediction techniques currently available, particularly in the testing of unseen proteins. Also, our model can recognize crucial sites of proteins, such as surface sites for binding and active sites for catalysis.

10.
Int J Biol Macromol ; 271(Pt 1): 132537, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38821806

RESUMEN

Cyanidin-3-O-glucoside (C3G) is a type of water-soluble flavonoid compound that is abundantly found in fruits and vegetables. C3G possesses numerous biological activities, however, it is prone to breakdown under environmental conditions. To overcome these issues, we developed nano-nutriosome (NS) carriers created by vortex-mixing and probe-sonication techniques for C3G encapsulation in which the phospholipid and Nutriose® FB06 were chosen as carrier material, and guar gum (GG) as a coating material to formulate a unilamellar and multicompartment structure. This study aimed to develop and evaluate C3G-loaded nano-nutriosomes coated by GG (GG-C3G-NS) for improving physicochemical stability, antioxidant activity, cellular uptake, and controlled release properties. The C3G-NS and GG-C3G-NS are nanosized (143.47 to 154.13 nm), with high encapsulation efficiency (>93.31 %). The NS carriers successfully encapsulated C3G which was confirmed by transmission electron microscopy, differential scanning calorimetry, and Fourier transform infrared spectroscopy. C3G showed more stability in storage, thermal, pH, ionic, and oxidative conditions. Furthermore, the NS exhibited a better-controlled release of C3G in different food stimulant conditions and in vitro release study. Additionally, NS systems enhanced cellular uptake and showed no cytotoxicity. Overall, GG-NS could be a promising nanocarrier for improving the stability, controlled release, and antioxidant activity of bioactive compounds.


Asunto(s)
Antocianinas , Antioxidantes , Galactanos , Mananos , Gomas de Plantas , Gomas de Plantas/química , Galactanos/química , Antocianinas/química , Antocianinas/farmacología , Mananos/química , Antioxidantes/química , Antioxidantes/farmacología , Portadores de Fármacos/química , Nanopartículas/química , Liberación de Fármacos , Humanos , Concentración de Iones de Hidrógeno
11.
Abdom Radiol (NY) ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38839650

RESUMEN

PURPOSE: To investigate the renal fat deposition on Dixon-based magnetic resonance imaging (MRI) and to explore the predictive value of renal fat biomarkers of magnetic resonance (MR-RFBs) for early kidney damage in obesity. METHODS: This prospective study included 56 obese volunteers and 47 non-obese healthy volunteers. All volunteers underwent renal magnetic resonance examinations. The differences in MR-RFBs [including renal proton density fat fraction (PDFF), renal sinus fat volume (RSFV), and perirenal fat thickness (PRFT)] measured on Dixon-based MRI between the obese and non-obese volunteers were analyzed using a general linear model, taking sex, age, diabetes, and hypertension as covariates. The relationship between estimated glomerular filtration rate (eGFR) and demographic, laboratory, and imaging parameters in obese volunteers was examined by correlation analysis. RESULTS: Obese volunteers had higher MR-RFBs than non-obese volunteers after controlling for confounders (all p < 0.001). Renal PDFF (r = - 0.383; p = 0.004), RSFV (r = - 0.368; p = 0.005), and PRFT (r = - 0.451; p < 0.001) were significantly negatively correlated with eGFR in obesity. After adjusting for age, sex, body mass index, diabetes, hypertension, visceral adipose tissue, subcutaneous adipose tissue, renal PDFF, and RSFV, PRFT remained independently negatively associated with eGFR (ß = - 0.587; p = 0.003). CONCLUSIONS: All MR-RFBs are negatively correlated with eGFR in obesity. The MR-RFBs, especially PRFT, may have predictive value for early kidney damage in obesity.

12.
Abdom Radiol (NY) ; 48(12): 3728-3745, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37750923

RESUMEN

OBJECTIVES: Parenchymal-sparing hepatectomy (PSH) is recommended in patients with colorectal liver metastases (CRLM). Based on the principle of PSH, to investigate the impact of anatomical resection (AR) and non-anatomic resection (NAR) on the outcome of CRLM and to evaluate the potential prognostic impact of three peritumoral imaging features. METHODS: Fifty-six patients who had abdominal gadoxetic acid-enhanced magnetic resonance imaging (MRI) before CRLM surgery were included in this retrospective research. Peritumoral early enhancement, peritumoral hypointensity on hepatobiliary phase (HBP), and biliary dilatation to the CRLM at MRI were evaluated. Survival estimates were calculated using the Kaplan-Meier method, and multivariate analysis was conducted to identify independent predictors of liver recurrence-free survival (LRFS), recurrence-free survival (RFS) and overall survival (OS). RESULTS: NAR had a lower 3-year LRFS compared with AR (36.6% vs. 78.6%, p = 0.012). No significant differences were found in 3-year RFS (34.1% vs. 41.7%) and OS (61.7% vs. 81.3%) (p > 0.05). In NAR group, peritumoral early enhancement was associated with poor LRFS (p = < 0.001, hazard ratio [HR] = 6.260; 95% confidence interval [CI], 2.322,16.876]) and poor RFS (p = 0.035, HR =2.516; 95% CI, 1.069,5.919). No independent predictors of CRLM were identified in the AR group. CONCLUSIONS: In patients with CRLM, peritumoral early enhancement was a predictor of LRFS and RFS after NAR according to the principle of PSH.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Humanos , Pronóstico , Hepatectomía/métodos , Estudios Retrospectivos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patología
13.
J Agric Food Chem ; 70(51): 16253-16262, 2022 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-36519893

RESUMEN

Anthocyanins are natural water-soluble pigments that widely exist in plants, with various biological activities, including antioxidant, anti-obesity, and anti-diabetic activities. Currently, monomeric anthocyanins are mainly obtained through natural sources, which limits their availability. In the biosynthesis of anthocyanins, anthocyanin methyltransferases are recognized to play important roles in the water solubility and structural stability of anthocyanins. Blueberries are a rich source of anthocyanins with more than 30 chemical structures. However, the enzymes that were responsible for the methylation of anthocyanidin cores in blueberries had not been reported. Here, blueberries (Vaccinium corymbosum) have been selected as the candidate for characterization of the key enzyme. Phylogenic analysis, enzymatic activity assay, homology modeling, molecular simulation, protein expression and purification assay, site-directed mutation, isothermal titration calorimetry assay, and enzyme kinetic assay were used to identify the enzymatic function and molecular mechanism of VcOMT, which was responsible for the methylation of anthocyanidin cores. VcOMT could use delphinidin as a substrate but not cyanidin, petunidin, anthocyanins, flavonols, and flavonol glycosides. Ile191 and Glu198 were both identified as important amino acid residues for the binding interactions of anthocyanidins with VcOMT.


Asunto(s)
Arándanos Azules (Planta) , Arándanos Azules (Planta)/química , Antocianinas/química , Metiltransferasas/genética , Glicósidos/análisis , Antioxidantes/análisis , Flavonoles/análisis , Frutas/química
14.
Front Endocrinol (Lausanne) ; 13: 995028, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36246918

RESUMEN

Backgrounds: Ectopic fat deposition is closely related to chronic kidney disease (CKD). Currently, there are few population studies that have been conducted to determine the relationship between renal parenchyma fat deposition and the risk of CKD among patients with type 2 diabetes mellitus (T2DM). Therefore, we employed magnetic resonance imaging (MRI) to detect renal parenchyma fat content in individuals with T2DM, expressed as renal fat fraction (FF), to explore whether renal FF is an important risk factor for CKD in patients with T2DM. Methods: In this cross-sectional study, 189 subjects with T2DM were enrolled. CKD was defined as the estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2. Measurement of the renal FF was performed on a 3.0-T MRI (MAGNETOM Skyra, Siemens, Erlangen, Germany). Binary logistic regression was used to determine the association between tertiles of renal FF and risk of CKD. Receiver-operator characteristic (ROC) curves were constructed to evaluate the sensitivity and specificity of renal FF in detecting CKD in T2DM patients. Results: The patients were divided into three groups according to tertiles of the renal FF level (2.498 - 7.434). As renal FF increases, patients tend to be older, and more abdominally obese, with a decreased eGFR (p<0.05). After adjustment for potential confounders, patients in the highest tertile of renal FF had a significantly increased risk of CKD than those in the lowest tertile (odds ratio (OR) = 3.98, 95% confidence interval (CI) = 1.12 - 14.09, p = 0.032), and the area under the ROC curve for this model was 0.836 (0.765-0.907). Conclusions: The renal FF is significantly independently associated with CKD in patients with T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Estudios Transversales , Diabetes Mellitus Tipo 2/patología , Tasa de Filtración Glomerular , Humanos , Riñón/diagnóstico por imagen , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico
15.
J Agric Food Chem ; 69(28): 7841-7850, 2021 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-34139848

RESUMEN

The present study is aimed to clarify the absorption and metabolism properties of pelargonidin-based anthocyanins. Results showed that pelargonidin-3-O-rutinoside (Pg3R) was absorbed in its intact form after oral administration and reached a maximum plasma concentration of 175.38 ± 55.95 nM at 60 min. Three main metabolites were identified in plasma, including Pg3R-monoglucuronide (m/z 755.2046), Pg3R-hydroxylated (m/z 595.1644), and Pg3R-demethylated (m/z 565.1569) metabolites. The plasma concentration of the Pg3R-demethylated metabolite (57.04 ± 23.15 nM) was much higher than that of other two metabolites, indicating that demethylation was the main metabolic pathway for Pg3R, while the glucuronide conjugate was detected as the dominant metabolic form of pelargonidin-3-O-glucoside (Pg3G). The bioavailability of Pg3R (1.13%) was fourfold higher than that of Pg3G (0.28%), demonstrating that anthocyanins linked to the rutinoside may exhibit higher bioavailability than that of glucoside. In vitro transport study unveiled that passive diffusion and active efflux were involved in the absorption of Pg3R and Pg3G.


Asunto(s)
Antocianinas , Animales , Antocianinas/metabolismo , Disponibilidad Biológica , Células CACO-2 , Humanos , Ratas , Ratas Sprague-Dawley
16.
J Agric Food Chem ; 69(16): 4663-4673, 2021 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-33787249

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) has become a universal health issue, whereas there is still a lack of widely accepted therapy until now. Clinical research studies have shown that blueberry could effectively regulate the lipid metabolism, thereby improving obesity-related metabolic syndromes; however, the specific active substances and mechanisms remain unclear. Herein, the effects of the major 10 kinds of anthocyanins from blueberry against NAFLD were investigated using an free fatty acid (FFA)-induced cell model. Among these anthocyanins, malvidin-3-O-glucoside (M3G) and malvidin-3-O-galactoside (M3Ga) could remarkably ameliorate FFA-induced lipid accumulation. Besides, M3G and M3Ga also inhibited oxidative stress via suppressing reactive oxygen species and superoxide anion overproduction, increasing glutathione levels, and enhancing activities of antioxidant enzymes. Further studies unveiled that the representative anthocyanin M3G-upregulated transcription factor EB (TFEB)-mediated lysosomal function possibly interacted with TFEB and activated the Nrf2/ARE (antioxidant responsive element) signaling pathway. Overall, this study enriched the knowledge about the health-promoting effects of blueberry anthocyanins against NAFLD and provided ideas for the development of functional foods of blueberry anthocyanins.


Asunto(s)
Arándanos Azules (Planta) , Enfermedad del Hígado Graso no Alcohólico , Antocianinas , Lisosomas , Factor 2 Relacionado con NF-E2/genética , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genética , Transducción de Señal
17.
Food Funct ; 11(10): 8527-8536, 2020 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-33000849

RESUMEN

Obesity is a chronic disease that has been causing serious problems all over the world. However, there is a lack of available therapeutic approaches to treat obesity. The FDA-approved drug orlistat has severe side effects, such as abdominal pain, flatulence and oily stool. As the therapeutic target of orlistat is pancreatic lipase, there is an urgent need for discovery of new pancreatic lipase inhibitors from natural sources that have reduced side effects compared with orlistat. In this study, ultrafiltration in combination with molecular simulation and spectroscopy was reported as an effective approach for identifying new pancreatic lipase inhibitors from anthocyanin-rich berry sources. Using this approach, four monomeric anthocyanins cyanidin-3-O-arabinoside (C3A), cyanidin-3-O-galactoside (C3Ga), peonidin-3-O-arabinoside (Pn3A) and peonidin-3-O-galactoside (Pn3Ga) from cranberries were discovered as potent pancreatic lipase inhibitors. These four cranberry anthocyanins were shown to form hydrophobic interactions and hydrogen bonds with pocket amino acid residues in molecular docking and molecular dynamics simulations. C3A showed greater impact on secondary structures of the enzyme and showed higher binding capacity with the enzyme compared with C3Ga, Pn3A and Pn3Ga as observed by CD and fluorescence spectroscopy. The structure-activity relationships were then investigated and summarized as both the structures of the B ring and glycosyl group were related to the inhibitory activities of anthocyanins. In short, our results suggested that cranberry anthocyanins could be developed as food supplements to facilitate the prevention and treatment of obesity.


Asunto(s)
Antocianinas/farmacología , Inhibidores Enzimáticos/farmacología , Lipasa/antagonistas & inhibidores , Páncreas/enzimología , Extractos Vegetales/química , Vaccinium macrocarpon/química , Animales , Antocianinas/química , Antocianinas/aislamiento & purificación , Dicroismo Circular , Suplementos Dietéticos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Frutas/química , Galactósidos/química , Galactósidos/aislamiento & purificación , Galactósidos/farmacología , Lipasa/química , Lipasa/metabolismo , Modelos Moleculares , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Relación Estructura-Actividad , Porcinos , Ultrafiltración
18.
Food Funct ; 11(4): 2910-2923, 2020 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-32219283

RESUMEN

Human Pancreatic Amylase (HPA) is an important target for prevention and treatment of type 2 diabetes. Acarbose is a currently available drug acting as a HPA inhibitor, but its gastrointestinal side-effects cannot be neglected. Thus, developing novel HPA inhibitors with no side-effects is of great importance. Herein, we adopted a structure-based design approach and discovered a potent HPA inhibitor, malvidin 3-O-arabinoside (M3A), from the natural anthocyanin database. We identified M3A as an effective HPA inhibitor through virtual screening, enzyme activity and enzyme kinetic assays. We reported the structure and activity relationships as both the anthocyanidin core and glucosyl group affected the HPA inhibitory effect of anthocyanins. Molecular dynamics studies indicated that the HPA inhibition of M3A occurred via its binding to the HPA key catalytic residues Arg195 and Asp197 through stable hydrogen bonding. In addition, M3A was found to reduce α-helix fractions and increase ß-sheet fractions in CD spectrometry. Further in vivo studies showed that M3A significantly ameliorated the postprandial blood glucose level. Taken together, our results provide new insights into the development of novel HPA inhibitors from natural sources as food supplements for type 2 diabetes.


Asunto(s)
Amilasas/antagonistas & inhibidores , Antocianinas/química , Diabetes Mellitus Tipo 2/prevención & control , Inhibidores Enzimáticos/química , Páncreas/enzimología , Acarbosa/química , Animales , Bases de Datos Factuales , Alimentos Funcionales , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Relación Estructura-Actividad , Interfaz Usuario-Computador
19.
J Agric Food Chem ; 68(46): 13025-13037, 2020 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-31322351

RESUMEN

Increasing evidence indicates that anthocyanins exert beneficial effects on type 2 diabetes (T2D), but the underlying mechanism remains unclear. Herein, the hyperglycemia-lowering effect of Pg3G derived from wild raspberry was investigated on high-glucose/high-fat (HG+HF)-induced hepatocytes and db/db diabetic mice. Our results indicated that Pg3G promoted glucose uptake in HG+HF-induced hepatocytes. Moreover, Pg3G induced autophagy, whereas autophagy inhibitors blocked the hypoglycemic effect of Pg3G. Transcriptional factor EB (TFEB) was found to be linked to Pg3G-induced autophagy. In vivo study showed that Pg3G treatment contributed to the improvement of glucose tolerance, insulin sensitivity, and induction of autophagy. Furthermore, Pg3G not only modified the gut microbiota composition, as indicated by an increased abundance of Prevotella, and elevated Bacteroidetes/Firmicutes ratio, but also strengthened the intestinal barrier integrity. This study unveils a novel mechanism that Pg3G attenuates hyperglycemia through inducing autophagy and modulating gut microbiota, which implicates a potential nutritional intervention strategy for T2D.


Asunto(s)
Antocianinas/administración & dosificación , Autofagia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Hipoglucemiantes/administración & dosificación , Extractos Vegetales/administración & dosificación , Rubus/química , Animales , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/crecimiento & desarrollo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiología , Diabetes Mellitus Tipo 2/fisiopatología , Frutas/química , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL
20.
Int J Biol Macromol ; 154: 380-389, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32194101

RESUMEN

Polysaccharides and fruit extracts are applied in dairy products to enhance their nutritional property, but the effects of such formulations on the functions and biological activities are yet to be explored. Therefore, this study was aimed at evaluating the effect of interactions among milk protein (beta-lactoglobulin; BLG), polysaccharides (pectin, P; chitosan, CH), and anthocyanin (pelargonidin-3-O-glucoside; P3G) in improving the bioavailability and biological activity of P3G. After gastrointestinal digestion (GID), the content of free P3G in different model solutions were as follows: P3G-alone (73.59 µg/mL), P3G-P (66.59 µg/mL), P3G-CH (36.72 µg/mL), P3G-BLG (64.92 µg/mL), P3G-P-BLG (64.92 µg/mL), and P3G-CH-BLG (39.61 µg/mL). Less amount of free P3G in model solutions indicated increased complex formation of P3G with protein and/or polysaccharides during GID. These complexes resulted in protection and progressive release of P3G in the gastrointestinal tract. Chitosan exhibited more protection to P3G compared with P and BLG. In addition, α-glucosidase inhibitory activity and ROS scavenging activities of conjugated-P3G samples were potentially augmented after GID. However, the presence of polysaccharides and protein in the model solutions did not show any negative effect on the biological activity of P3G. Thus, pure P3G can be used as a nutritional ingredient in dairy industries.


Asunto(s)
Antocianinas/farmacología , Quitosano/química , Digestión/efectos de los fármacos , Inhibidores de Glicósido Hidrolasas/farmacología , Lactoglobulinas/química , Pectinas/química , Antocianinas/farmacocinética , Antioxidantes , Disponibilidad Biológica , Tracto Gastrointestinal/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacocinética , Células Hep G2 , Humanos , alfa-Glucosidasas/metabolismo
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