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1.
Crit Rev Food Sci Nutr ; : 1-13, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797201

RESUMO

The controlled release of guest molecules from cyclodextrin (CD) inclusion complexes is very important for specific industrial applications in foods, medicine, cosmetics, textiles, agriculture, environmental protection, and chemical materials. The term "controlled release" encompasses several related methods, including those referred to as immediate release, sustained release and targeted release. Many different CD-based controlled release systems are currently used in practical applications. CD inclusion complexes, CD coupling, supramolecular hydrogels, and supramolecular micelles are among the most common. This review systematically introduces the principles and applications of CD-based controlled release systems, providing a theoretical basis for improving the bioavailability of effective substances and broadening their range of application.

2.
Food Funct ; 12(22): 11290-11302, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34635904

RESUMO

Butyrate has recently emerged as a promising substance for the therapy of colitis. To overcome the shortcomings implicated in the existing delivery systems of butyrate, we utilized butyrylated starch to specifically deliver butyrate to the colon. Herein, we describe the stable loading of butyrate via chemical bonds with a heterogeneous distribution throughout the particle. Butyrylated starch supply increased butyrate as well as total short-chain fatty acid contents at the end of the intervention period. Moreover, butyrylated starch showed multiple effects on the suppression of DSS-induced colitis. From the observation of the gut-liver axis, reduced hepatic inflammation and hepatocyte damage further confirmed alleviated colonic inflammation. Given that butyrylated starch has the combined effects of specific release of butyrate in the colon and extra supply of fermentable substrates for gut microbiota, this work provides an effective strategy for the assistant therapy of colitis.

3.
Front Microbiol ; 12: 708480, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335544

RESUMO

Marine extremophiles produce cold-adapted and/or salt-tolerant enzymes to survive in harsh conditions. These enzymes are naturally evolved with unique structural features that confer a high level of flexibility, solubility and substrate-binding ability compared to mesophilic and thermostable homologs. Here, we identified and characterized an amylase, SdG5A, from the marine bacterium Saccharophagus degradans 2-40 T . We expressed the protein in Bacillus subtilis and found that the purified SdG5A enabled highly specific production of maltopentaose, an important health-promoting food and nutrition component. Notably, SdG5A exhibited outstanding cold adaptation and salt tolerance, retaining approximately 30 and 70% of its maximum activity at 4°C and in 3 M NaCl, respectively. It converted 68 and 83% of starch into maltooligosaccharides at 4 and 25°C, respectively, within 24 h, with 79% of the yield being the maltopentaose. By analyzing the structure of SdG5A, we found that the C-terminal carbohydrate-binding module (CBM) coupled with an extended linker, displayed a relatively high negative charge density and superior conformational flexibility compared to the whole protein and the catalytic domain. Consistent with our bioinformatics analysis, truncation of the linker-CBM region resulted in a significant loss in activities at low temperature and high salt concentration. This highlights the linker-CBM acting as the critical component for the protein to carry out its activity in biologically unfavorable condition. Together, our study indicated that these unique properties of SdG5A have great potential for both basic research and industrial applications in food, biology, and medical and pharmaceutical fields.

4.
Crit Rev Food Sci Nutr ; : 1-12, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34423705

RESUMO

Wheat flour can form dough with a three-dimensional viscoelastic structure that is responsible for gas holding during fermentation and oven-rise, creating a typical fixed, open-cell foam structure of bread after baking. As the major components of dough, the continuous reticular skeleton formed by gluten proteins and the concentrated starch granules entrapped in gluten matrix predominantly determine dough rheological behaviors and bread qualities. This review surveys the latest literatures and draws out a conclusion from a plethora of information related to the filling effects of starch granules on gluten matrix and the cross-linking mechanisms between gluten proteins and starch granules, which is of great significance to provide sufficient scientific knowledge for development of bread with satisfactory attributes and quality control of end products.

5.
Food Chem ; 362: 130240, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34119950

RESUMO

The alleviating role of starch derivatives on the quality deterioration of frozen steamed bread dough was investigated in terms of derivative structure, the bread characteristics and dough properties including freezable water contents, yeast activity as well as dough viscoelasticity. The addition of starch derivatives including short-clustered maltodextrin (SCMD), DE2 maltodextrin (MD) and pregelatinized starch (PGS) significantly increased the specific volume and decreased the hardness of steamed bread compared with Control bread after 8-week frozen storage. Lower freezable water content was found in PGS dough than SCMD dough, which was consistent with the results of water absorption index of starch derivatives. The analysis of dough gassing rate and yeast survival ratio demonstrated SCMD could provide more cryoprotection for yeast cells. Meanwhile, a higher elastic module and a more continuous gluten-network structure of SCMD dough were found after 8-week frozen storage. These results indicated starch derivatives especially SCMD were promising to be used as the alternative improvers in frozen dough production.


Assuntos
Pão/análise , Pão/normas , Qualidade dos Alimentos , Congelamento , Amido/farmacologia , Tecnologia de Alimentos , Glutens/química , Saccharomyces cerevisiae/efeitos dos fármacos , Amido/química , Vapor , Viscosidade/efeitos dos fármacos , Água/química , Fermento Seco/análise
6.
J Agric Food Chem ; 69(20): 5755-5763, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33988022

RESUMO

The 1,4-α-glucan branching enzyme (GBE, EC 2.4.1.18) catalyzes the formation of α-1,6 branching points in starch and plays a key role in synthesis. To obtain mechanistic insights into the catalytic action of the enzyme, we first determined the crystal structure of GBE from Rhodothermus obamensis STB05 (RoGBE) to a resolution of 2.39 Å (PDB ID: 6JOY). The structure consists of three domains: domain A, domain C, and the carbohydrate-binding module 48 (CBM48). An engineered truncated mutant lacking the CBM48 domain (ΔCBM48) showed significantly reduced ligand binding affinity and enzyme activity. Comparison of the structures of RoGBE with other GBEs showed that CBM48 of RoGBE had a longer flexible loop. Truncation of the flexible loops resulted in reduced binding affinity and activity, thereby substantiating the importance of the optimum loop structure for catalysis. In essence, our study shows that CBM48, especially the flexible loop, plays an important role in substrate binding and enzymatic activity of RoGBE. Further, based on the structural analysis, kinetics, and activity assays on wild type and mutants, as well as homology modeling, we proposed a mechanistic model (called the "lid model") to illustrate how the flexible loop triggers substrate binding, ultimately leading to catalysis.


Assuntos
Enzima Ramificadora de 1,4-alfa-Glucana , Rhodothermus , Enzima Ramificadora de 1,4-alfa-Glucana/metabolismo , Glucanos , Rhodothermus/metabolismo , Especificidade por Substrato
7.
Carbohydr Polym ; 262: 117968, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33838833

RESUMO

Enzymatically rearranging α-1,4 and α-1,6 glycosidic bonds in starch is a green approach to regulating its digestibility. A two-step modification process successively catalyzed by 1,4-α-glucan branching enzymes (GBEs) from Rhodothermus obamensi STB05 (Ro-GBE) and Geobacillus thermoglucosidans STB02 (Gt-GBE) was investigated as a strategy to reduce the digestibility of corn starch. This dual GBE modification process caused a reduction of 25.8 % in rapidly digestible starch fraction in corn starch, which were more effective than single GBE-catalyzed modification with the same duration. Structural analysis indicated that the dual GBE modified product contained higher branching density, more abundant short branches, and shorter external chains than those in single GBE-modified product. These results demonstrated that a moderate Ro-GBE treatment prior to starch gelatinization caused several suitable alterations in starch molecules, which promoted the transglycosylation efficiency of the following Gt-GBE treatment. This dual GBE-catalyzed modification process offered an efficient strategy for regulating starch digestibility.


Assuntos
Enzima Ramificadora de 1,4-alfa-Glucana/química , Glicosídeos/química , Amido/química , Enzima Ramificadora de 1,4-alfa-Glucana/metabolismo , Amilose/química , Amilose/metabolismo , Bacillaceae/enzimologia , Digestão , Glicosídeos/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Estrutura Molecular , Rhodothermus/enzimologia , Amido/metabolismo
8.
Carbohydr Polym ; 262: 117926, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33838805

RESUMO

Double emulsions are promising carrier systems for foods, pharmaceuticals, and cosmetics. However, their limited stability hinders their practical applications. We used gelatinized starch to develop stable double emulsions as carrier materials. The oil/water/water (O/W/W) double emulsions were formed by 5 wt% native corn starch, while oil/water/oil (O/W/O) double emulsions were formed by 7 wt% native corn starch and high-amylose starch with 60 % and 75 % amylose contents investigated by optical microscopy. Furthermore, the storage stability of double emulsions was revealed by droplet size distribution, microstructure, backscattering, rheological profiles, and low-field nuclear magnetic resonance (LF-NMR) imaging. Results confirmed that the O/W/O double emulsions stabilized by 7 wt% native corn starch had a smaller mean droplet size (11.400 ± 0.424 µm) and excellent storage stability (14 days) than O/W/W and O/W/O double emulsions prepared with high-amylose starch. Such unique double emulsions prepared with gelatinized native corn starch are good candidates of carrier materials.


Assuntos
Emulsões/química , Gelatina/química , Amido/química , Amilose/química , Portadores de Fármacos/química , Humanos , Espectroscopia de Ressonância Magnética/métodos , Tamanho da Partícula , Reologia , Água/química
9.
Mitochondrial DNA B Resour ; 6(2): 349-350, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33659674

RESUMO

Potentilla parvifolia Fisch. (Rosaceae) is one of the genuine medicinal materials in Qinghai-Tibet Plateau, China. Here we report the first chloroplast (cp) genome of P. parvifolia using Illumina NovaSeq 6000 platform. The length of its complete cp genome is 152,898 bp, containing four sub-regions; a large single copy region (LSC) of 84,160 bp and a small single copy region (SSC) of 18,128 bp are separated by a pair of inverted repeat regions (IRs) of 25,305bp. The complete cp genome of P. parvifolia contains 130 genes, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the cp genome is 37.2%. The phylogenetic analysis, based on 17 cp genomes, suggested that P. parvifolia is closely related to P. fruticosa L. and Fragaria species.

10.
Food Chem ; 352: 129350, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33657481

RESUMO

Fermented cassava products are important starchy food staples in South America. The quality of the products is affected by the baking expansion ability of the dough, which is in turn influenced by the starch fermentation process and drying method employed. We investigated the structural properties of cassava starch after different fermentation and drying treatments, and the effect of starch structure on scalding of dough and baking expansion ability. Fermentation combined with either exposure to sunlight or UV light treatment resulted in high cassava starch baking expansion. Moreover, we observed decreased crystallinity and increased disordered crystalline regions with lower molecular weight in the two types of starch-fermented combined with sunlight or UV light treatment-and both appeared to have a continuous network structure and polarized cross in scalded dough, which are conducive to holding gas and losing water, thus promoting high baking expansibility.


Assuntos
Manipulação de Alimentos , Manihot/química , Amido/química , Dessecação , Fermentação , Manihot/efeitos da radiação , Peso Molecular , Luz Solar , Raios Ultravioleta
11.
Food Chem ; 354: 129475, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-33744660

RESUMO

The α-amylases are the most widely used industrial enzymes, and are particularly useful as liquifying enzymes in industrial processes based upon starch. Since starch liquefication is carried out at evaluated temperatures, typically above 60 °C, there is substantial demand for thermostable α -amylases. Most naturally occurring α -amylases exhibit moderate thermostability, so substantial effort has been invested in attempts to increase their thermostability. One structural feature that has the potential to increase protein thermostability is the introduction of salt bridges. However, not every salt bridge contributes to protein thermostability. The salt bridges in amylases have their characteristics in terms of distribution, configuration and location. The summary of these features helps to introduce new salt bridges based on the characteristics. This review focuses on salt bridges of α-amylases, both naturally present and introduced using mutagenesis. Its aim is to provide a bird's eye view of distribution, configuration, location of desirable salt bridges.


Assuntos
Sais/química , alfa-Amilases/metabolismo , Bacillus licheniformis/enzimologia , Sítios de Ligação , Estabilidade Enzimática , Metais/química , Simulação de Dinâmica Molecular , Temperatura , alfa-Amilases/química
12.
Int J Biol Macromol ; 175: 254-261, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33561459

RESUMO

The efficiency of enzymatic cyclodextrin production using cyclodextrin glycosyltransferases (CGTases) is limited by product inhibition. In this study, maltose binding site 2 (MBS2) of the ß-CGTase from Bacillus circulans STB01 was modified to decrease product inhibition. First, two point mutants were prepared at position 599 (A599V and A599N). Then, two double mutants incorporating alanine at position 633 (A599N/Y633A and A599V/Y633A) were prepared. Finally, the entire MBS2 region was replaced by that of the α-CGTase from Paenibacillus macerans JFB05-01 to form multipoint mutant MBS2 ߠ→ α. All five mutants exhibited mixed-type product inhibition, although both the competitive and uncompetitive components of this inhibition were decreased. The total cyclization activities of A599N, A599V and A599V/Y633A were 15.6%, 76.8% and 70.9% lower than that of the wild-type, respectively, while that of A599N/Y633A was 22.4% higher. Among the mutants, only MBS2 ߠ→ α showed catalytic efficiency (kcat/Km) comparable with that of the wild-type. Moreover, A599N, A599N/Y633A and MBS2 ߠ→ α produced cyclodextrin yields 13.1%, 15.8% and 19.7% greater than that of the wild-type, respectively. These results suggest that A599N, A599N/Y633A and MBS2 ߠ→ α may be more suitable than the wild-type for cyclodextrin production.


Assuntos
Bacillus/metabolismo , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Maltose/metabolismo , Bacillus/genética , Proteínas de Bactérias/química , Sítios de Ligação/genética , Ciclização/genética , Ciclodextrinas/metabolismo , Cinética , Proteínas Ligantes de Maltose/genética , Proteínas Ligantes de Maltose/metabolismo , Modelos Moleculares , Mutagênese Sítio-Dirigida/métodos , Mutação/genética , Paenibacillus/genética , Especificidade por Substrato/genética , beta-Ciclodextrinas/química
13.
J Sci Food Agric ; 101(9): 3742-3748, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33301206

RESUMO

BACKGROUND: Designing a high-concentration (50%, w/w) maltodextrin saccharification process is a green method to increase the productivity of maltose syrup. RESULTS: In this study, a temperature-mediated two-step process using ß-amylase and pullulanase was investigated as a strategy to improve the efficiency of saccharification. During the saccharification process, both pullulanase addition time and temperature adjustment greatly impacted the final maltose yield. These results indicated that an appropriate ß-amylolysis in the first stage (the first 8 h) was required to facilitate saccharification process, with the maltose yield of 8.46% greater than that of the single step saccharification. Molecular structure analysis further demonstrated that a relatively low temperature (50 °C), as compared with a normal temperature (60 °C), in the first stage resulted in a greater number of chains polymerized by at least seven glucose units and a less heterogeneity system within the residual substrate. The molecular structure of the residual substrate might be beneficial for the subsequent cooperation between ß-amylase and pullulanase in the following 40 h (second stage). CONCLUSION: Over a 48 h saccharification, the temperature-mediated two-step process dramatically increased the conversion rate of maltodextrin and yielded significantly more maltose and less byproduct, as compared with a constant-temperature process. The two-step saccharification process therefore offered an efficient and green strategy for maltose syrup production in industry. © 2020 Society of Chemical Industry.


Assuntos
Glicosídeo Hidrolases/química , Maltose/análise , Polissacarídeos/química , Biocatálise , Glucose , Hidrólise , Temperatura
14.
J Agric Food Chem ; 69(1): 354-367, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33350823

RESUMO

Dietary starch is usually associated with elevated postprandial glycemic response. This is a potential risk factor of type 2 diabetes. Here, a 1,4-α-glucan branching enzyme (GBE) was employed to reassemble α-1,4 and α-1,6 glycosidic bonds in starch molecules. Structural characterization showed that GBE-catalyzed molecular reassembly created an innovative short-clustered maltodextrin (SCMD), which showed a dense internal framework along with shortened external chains. Such short-clustered molecules obstructed digestive enzymes attack and displayed dramatically reduced digestibility. Therefore, SCMD was served as a dietary starch substitute to improve postprandial glucose homeostasis. A 22.3% decrease in glycemic peak was therefore detected in ICR mice following SCMD intake (10.7 mmol/L), compared with that in the control (13.8 mmol/L). Moreover, an attenuated insulin response (40.5% lower than that in control) to SCMD intake was regarded suitable for diabetes management. These novel discoveries demonstrate that enzymatically rebuilding starch molecules may be a meaningful strategy for diabetes management.


Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Polissacarídeos/metabolismo , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Índice Glicêmico , Homeostase , Humanos , Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Polissacarídeos/química , Período Pós-Prandial , Amido/metabolismo
15.
J Agric Food Chem ; 68(47): 13791-13797, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33166453

RESUMO

Disulfide bonds play crucial roles in thermostabilization, recognition, or activation of proteins. They are vital in maintaining the respective conformations of globular structures, thereby enhancing thermostability. Bioinformatic approaches provide practical strategies to build disulfide bonds based on structural information. We constructed nine mutants by rational analysis of the 1,4-α-glucan branching enzyme (EC 2.4.1.18) from Geobacillus thermoglucosidans STB02, which catalyzes the synthesis of α-1,6-glucosidic bonds by acting on α-(1,4) and/or α-(1,6) glucosidic linkages. Four of the mutations enhanced thermostability, and five of them had adverse or negligible effects on stability. Circular dichroism spectra and intrinsic fluorescence analysis showed that introducing disulfide bonds might only affect secondary structures. The results also demonstrated that the distances of Cα carbons and thiol groups, as well as the sequence between the two cysteines, need to be considered when designing disulfide bonds.


Assuntos
Enzima Ramificadora de 1,4-alfa-Glucana , Geobacillus , Enzima Ramificadora de 1,4-alfa-Glucana/metabolismo , Bacillaceae , Dissulfetos , Estabilidade Enzimática , Geobacillus/genética , Glucanos
16.
Food Funct ; 11(12): 10945-10953, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33245312

RESUMO

Resistant starch, a functional food ingredient, can improve the nutritional value of food products. In this study, the in vitro digestibility of starch from banana flour at four ripening stages was evaluated. The result showed that the resistant starch content of banana flour at ripening stage 1 was up to 81%. Furthermore, to explore the effect of resistant starch in the body, the in vivo digestibility of banana flour was investigated. The intake of banana flour at ripening stage 1 resulted in a nearly 70% decrease in the homeostasis model assessment of insulin resistance value, compared to that of the model group. By contrast, the genes related to glucokinase were upregulated by 66%, and the expression level of the insulin receptor gene was increased by more than 1.5 times that of the model group. Thus, natural banana flour has potential for controlling type 2 diabetes mellitus.


Assuntos
Digestão/fisiologia , Farinha/análise , Musa/química , Amido Resistente/metabolismo , Amido/metabolismo , Glicemia , Peso Corporal , Diabetes Mellitus Tipo 2 , Alimento Funcional , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Homeostase , Resistência à Insulina , Lipídeos/sangue , Valor Nutritivo
17.
J Agric Food Chem ; 68(44): 12400-12412, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33084325

RESUMO

Molecular structure of starch in daily diet is closely associated with diabetes management. By enzymatically reassembling α-1,4 and α-1,6 glycosidic bonds in starch molecules, we have synthesized an innovative short-clustered maltodextrin (SCMD) which slowly releases glucose during digestion. Here, we investigated the potential benefits of the SCMD-containing diet using diabetic db/db mice. As compared to a diet with normal starch, this dietary style greatly attenuated hyperglycemia and repaired symptoms associated with diabetes. Additionally, in comparison with acarbose (an α-glucosidase inhibitor) administration, the SCMD-containing diet more effectively accelerated brown adipose activation and improved energy metabolism of db/db mice. Furthermore, the SCMD-containing diet was a more suitable approach to improving the intestinal microflora than acarbose administration, especially the proliferation of Mucispirillum, Akkermansia, and Bifidobacterium. These results reveal a novel strategy for diabetes management based on enzymatically rebuilding starch molecules in the daily diet.


Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/metabolismo , Carboidratos da Dieta/metabolismo , Microbioma Gastrointestinal , Polissacarídeos/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Carboidratos da Dieta/análise , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos/química , Amido/metabolismo
18.
Food Chem ; 327: 126945, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32447131

RESUMO

This paper described a high-performance molecular test for the detection of Mycobacterium bovis (M. bovis) based on digital loop-mediated isothermal amplification (dLAMP). M. bovis is a persistent pathogen that causes zoonotic tuberculosis and can infect both animals and human beings. The detection of M. bovis in milk samples is critical for effective control and prevention of zoonotic diseases but there lacks effective and sensitive methods. Here, we developed a convenient and low-cost system for M. bovis detection in milk, which incorporated automated DNA extraction and dLAMP by interfacial emulsification technique. Versus real-time PCR, dLAMP provides higher accuracy and sensitivity for direct M. bovis detection in milk, offering a limit of detection of 14 CFU/mL within 2 h. The dLAMP system can become a powerful platform for the detection of pathogens in complex samples and provide more reliable guidance for food safety testing, epidemiological research and clinical diagnosis.


Assuntos
Leite/microbiologia , Mycobacterium bovis/isolamento & purificação , Animais , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da Polimerase em Tempo Real
19.
Int J Biol Macromol ; 159: 823-831, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32445823

RESUMO

Starch is the most significant carbon and energy reserve in plants and is also a sustainable feedstock for many industrial applications. Substantial research effort has been devoted to enhancing the yield and quality of starch. Over the past century, starch phosphorylation has aroused increasing interest as the only naturally occurring covalent modification in starch. Many studies have investigated the role of phosphorylation in starch metabolism and its impact on the starch granule. In this review, the two key enzymes involved in starch phosphorylation and their catalytic mechanisms are described at the molecular level; the vital roles of phosphorylation in starch degradation and biosynthesis are illuminated in detail; and the multiple influences of phosphorylation on starch composition, granule structure and physicochemical properties are discussed. This review systematically summarizes the importance of phosphorylation in starch metabolism, and describes the advanced methods used to precisely measure phosphate and increase the level of starch phosphorylation.


Assuntos
Metabolismo dos Carboidratos , Fenômenos Fisiológicos Vegetais , Amido/química , Amido/metabolismo , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Animais , Catálise , Enzimas/química , Enzimas/metabolismo , Humanos , Redes e Vias Metabólicas , Fenótipo , Fosforilação , Amido/biossíntese
20.
Mol Med Rep ; 21(6): 2615-2623, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32323789

RESUMO

Pancreatic encephalopathy (PE) is a common fatal complication of acute pancreatitis (AP). Proinflammatory cytokines such as tumor necrosis factor (TNF)­α and interleukin (IL)­6 are generated during AP, and act synergistically to promote PE and multisystem failure. Caerulein­induced AP provides a convenient model to explore the role of proinflammatory cytokines in PE. The aim of the present study was to examine the effect of the TNF­α inhibitor etanercept in PE models and elucidate the regulatory mechanisms. To model PE in vitro, rat hippocampal H19­7/IGF­IR neuronal cells were treated with 10 nmol/ml caerulein alone or in combination with etanercept (1, 10 or 100 µmol/ml). To model PE in vivo, rats were injected with 50 µg/kg caerulein alone or combined with 10 mg/kg etanercept. At 6 h after administration, it was noted that etanercept downregulated expression of TNF­α, IL­1ß and IL­6 by negatively regulating NF­κB (a master regulator of cytokine expression) signaling, and prevented the accumulation of reactive oxygen species. Conversely, etanercept promoted the expression of the neurotrophic and anti­inflammatory hypoxia­inducible factor 1 α (HIF­1α). In rat hippocampus, etanercept also reduced the levels of TNF­α, IL­1ß and IL­6, upregulated HIF­1α expression and inhibited the inflammatory response to reduce edema and neural necrosis. Together, these data suggested that etanercept could attenuate caerulein­induced PE, at least in part via suppression of NF­κB signaling and alleviation of oxidative stress.


Assuntos
Encefalopatias/patologia , Regulação para Baixo/efeitos dos fármacos , Etanercepte/farmacologia , Pâncreas/patologia , Animais , Encefalopatias/etiologia , Encefalopatias/metabolismo , Linhagem Celular , Ceruletídeo/toxicidade , Modelos Animais de Doenças , Hipocampo/citologia , Hipocampo/metabolismo , Hipocampo/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
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