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1.
Org Lett ; 26(10): 2114-2118, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38437731

RESUMO

Herein, we report a general and practical nickel-catalyzed deaminative alkylation of Katritzky salts with cyclopropyl alcohols via merging C-N and C-C bond activation. This protocol enables the formation of an alkyl-alkyl bond along with the generation of a versatile ketone functional group in a single operation, thus providing a convenient approach for accessing ß-alkyl ketones. This reaction is distinguished by its high functional group tolerance, broad substrate scope, and efficient late-stage derivatization of complex bioactive molecules.

2.
Food Funct ; 14(19): 8747-8760, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37698392

RESUMO

Curcumin has been proven to be an effective strategy for reducing inflammatory responses. However, low bioavailability and instability at the physiological pH have limited its anti-inflammatory activity in ulcerative colitis patients. In the present study, a complex of curcumin and konjac glucomannan (KGM) effectively inhibited intestinal inflammation and this effect was associated with KGM degradation degrees. Results demonstrated that treatment with the complex markedly mitigated colitis symptoms and decreased inflammatory cytokines levels, especially in the complex treatment groups with K110 (KGM treated in 110 °C) and konjac oligosaccharides (KOSs). Furthermore, increasing the KOS content in KOC (the complex of curcumin and KOS) promoted the gene expressions of the intestinal barrier and inhibited the gene expressions of inflammatory cytokines, as well as improved gut microbiota dysregulation. Overall, our studies suggest that the complex of curcumin and KGM exerts effective anti-inflammatory effects by regulating the intestinal immune response and modulating microbiota diversity and composition.

3.
Foods ; 12(12)2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37372594

RESUMO

Sesame is principally used to generate oil, which is produced by chemical refining or pressing. Sesame meal, as a main byproduct of sesame oil extraction, is usually discarded, causing resource waste and economic loss. Sesame meal is rich in sesame protein and three types of sesame lignans (sesamin, sesamolin, and sesamol). Sesame protein extracted via a physical method and an enzymic method has balanced amino acid composition and is an important protein source, and thus it is often added to animal feed and used as a human dietary supplement. Extracted sesame lignan exhibits multiple biological activities such as antihypertensive, anticancer, and cholesterol-lowering activities, and therefore it is used to improve the oxidative stability of oils. This review summarizes the extraction methods, functional activities, and comprehensive utilization of four active substances (sesame protein, sesamin, sesamolin, and sesamol) in sesame meal with the aim to provide theoretical guidance for the maximum utilization of sesame meal.

4.
Food Funct ; 14(13): 6187-6199, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37341480

RESUMO

The purpose of this study was to explore the protective effects of selenium containing soybean peptides (SePPs) on inflammatory bowel disease in colitis mice. During the experimental period, the mice were administered with SePPs for 14 days, and then treated with drinking water containing 2.5% dextran sodium sulfate (DSS) for 9 days, while the intervention of SePPs was continued. The results showed that low-dose SePPs (15 µg Se per kg per d bw) could effectively alleviate DSS-induced inflammatory bowel disease through the improvement of the antioxidant levels, reduction of inflammatory factor levels, and increase of tight junction protein expression of ZO-1 and occludin in the colon, thus improving the structure of the colon and strengthening the barrier function of the small intestine. Additionally, SePPs were found to significantly improve the production of short chain fatty acids (P < 0.05). Moreover, SePPs could improve intestinal microbiota diversity, significantly increasing the Firmicutes/Bacteroidetes ratio and the abundance of some beneficial genera, such as Lachnospiraceae_NK4A136_group and Lactobacillus (P < 0.05). Though high-dose SePPs (30 µg Se per kg per d bw) could improve DSS induced bowel disease, the effect was worse than that in the low-dose SePP group. These findings provide new insights into Se-containing peptides as a functional food against inflammatory bowel disease and dietary selenium supplementation.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Selênio , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Glycine max , Disbiose , Peptídeos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Colo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Inflamação/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
5.
Crit Rev Food Sci Nutr ; 63(23): 5985-6004, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35089848

RESUMO

Proteins/peptides and saccharides are two kinds of bioactive substances in nature. Recently, increasing attention has been paid in understanding and utilizing covalent interactions between proteins/peptides and saccharides. The products obtained through covalent conjugation of proteins/peptides to saccharides are shown to have enhanced functional attributes, such as better gelling property, thermostability, and water-holding capacity. Additionally, food-derived protein/peptide-saccharide covalent conjugates (PSCCs) also have biological activities, such as antibacterial, antidiabetic, anti-osteoporosis, anti-inflammatory, anti-cancer, immune regulatory, and other activities that are widely used in the functional food industry. Moreover, PSCCs can be used as packaging or delivery materials to improve the bioavailability of bioactive substances, which expands the development of food-derived protein and saccharide resources. Thus, this review was aimed to first summarize the current status of sources, classification structures of natural PSCCs. Second, the methods of chemical synthesis, reaction conditions, characterization and reagent formulations that improve the desired functional characteristics of food-derived PSCCs were introduced. Third, functional properties such as emulsion, edible films/coatings, and delivery of active substance, bio-activities such as antioxidant, anti-osteoporosis, antidiabetic, antimicrobial of food-derived PSCCs were extensively discussed.


Assuntos
Anti-Infecciosos , Carboidratos , Peptídeos , Antibacterianos , Proteínas , Anti-Infecciosos/química
6.
Crit Rev Food Sci Nutr ; 63(1): 125-144, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34251926

RESUMO

Osteoporosis is a public health concern and a cause of bone loss, increased risk of skeletal fracture, and a heavy economic burden. It is common in postmenopausal women and the elderly and is impacted by dietary factors, lifestyle and some secondary factors. Although many drugs are available for the treatment of osteoporosis, these therapies are accompanied by subsequent side effects. Hence, dietary interventions are highly important to prevent osteoporosis. This review was aimed to provide a comprehensive understanding of the roles of dietary nutrients derived from natural foods and of common dietary patterns in the regulation of osteoporosis. Nutrients from daily diets, such as unsaturated fatty acids, proteins, minerals, peptides, phytoestrogens, and prebiotics, can regulate bone metabolism and reverse bone loss. Meanwhile, these nutrients generally existed in food groups and certain dietary patterns also play critical roles in skeletal health. Appropriate dietary interventions (nutrients and dietary patterns) could be primary and effective strategies to prevent and treat osteoporosis across the lifespan for the consumers and food enterprises.


Assuntos
Fraturas Ósseas , Osteoporose , Feminino , Humanos , Idoso , Densidade Óssea , Osteoporose/prevenção & controle , Osteoporose/tratamento farmacológico , Fraturas Ósseas/prevenção & controle , Fitoestrógenos , Dieta
7.
Mikrochim Acta ; 189(12): 442, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36342547

RESUMO

An easily prepared fluoro-functionalized ionic covalent organic framework (F-iCOF) has been implemented into MALDI-TOF MS, enabling the highly selective enrichment and sensitive determination of perfluorinated sulfonate (PFS) contaminants in a rapid and convenient manner. The good thermal stability and excellent optical absorption properties of F-iCOF makes it a brilliant matrix with no background noise. Moreover, benefitting from the large surface area, appropriate pore size, good water dispersibility, and abundant fluorine atom and cationic characteristic of F-iCOF, it exhibited superior adsorption capacity and enrichment selectivity towards PFSs. Good signal responses for PFSs were obtained in the presence of various interfering compounds such as BSA, HA, or even more than 100-fold excess of glutamic acid and similar in structure sodium alkyl sulfonates, highlighting the specific selectivity of F-iCOF. Calibration curves for potassium perflurobutane sulfonate (PFBSK) in tap water and whole blood were established with good linear correlation in the range 1-500 pg mL-1. The limits of detection and quantification for PFBSK were as low as 0.04 pg mL-1 and 0.05 pg mL-1, respectively, which are comparable or better than the existing methods for the determination of PFSs.


Assuntos
Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Adsorção , Íons , Alcanossulfonatos , Água/química
8.
J Neurodev Disord ; 14(1): 32, 2022 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606697

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by restricted, repetitive behavior, and impaired social communication and interactions. However, significant challenges remain in diagnosing and subtyping ASD due in part to the lack of a validated, standardized vocabulary to characterize clinical phenotypic presentation of ASD. Although the human phenotype ontology (HPO) plays an important role in delineating nuanced phenotypes for rare genetic diseases, it is inadequate to capture characteristic of behavioral and psychiatric phenotypes for individuals with ASD. There is a clear need, therefore, for a well-established phenotype terminology set that can assist in characterization of ASD phenotypes from patients' clinical narratives. METHODS: To address this challenge, we used natural language processing (NLP) techniques to identify and curate ASD phenotypic terms from high-quality unstructured clinical notes in the electronic health record (EHR) on 8499 individuals with ASD, 8177 individuals with non-ASD psychiatric disorders, and 8482 individuals without a documented psychiatric disorder. We further performed dimensional reduction clustering analysis to subgroup individuals with ASD, using nonnegative matrix factorization method. RESULTS: Through a note-processing pipeline that includes several steps of state-of-the-art NLP approaches, we identified 3336 ASD terms linking to 1943 unique medical concepts, which represents among the largest ASD terminology set to date. The extracted ASD terms were further organized in a formal ontology structure similar to the HPO. Clustering analysis showed that these terms could be used in a diagnostic pipeline to differentiate individuals with ASD from individuals with other psychiatric disorders. CONCLUSION: Our ASD phenotype ontology can assist clinicians and researchers in characterizing individuals with ASD, facilitating automated diagnosis, and subtyping individuals with ASD to facilitate personalized therapeutic decision-making.


Assuntos
Transtorno do Espectro Autista , Processamento de Linguagem Natural , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/genética , Registros Eletrônicos de Saúde , Humanos , Fenótipo , Vocabulário
9.
Genes (Basel) ; 12(8)2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34440331

RESUMO

Human genetic disorders, such as Down syndrome, have a wide variety of clinical phenotypic presentations, and characterizing each nuanced phenotype and subtype can be difficult. In this study, we examined the electronic health records of 4095 individuals with Down syndrome at the Children's Hospital of Philadelphia to create a method to characterize the phenotypic spectrum digitally. We extracted Human Phenotype Ontology (HPO) terms from quality-filtered patient notes using a natural language processing (NLP) approach MetaMap. We catalogued the most common HPO terms related to Down syndrome patients and compared the terms with those from a baseline population. We characterized the top 100 HPO terms by their frequencies at different ages of clinical visits and highlighted selected terms that have time-dependent distributions. We also discovered phenotypic terms that have not been significantly associated with Down syndrome, such as "Proptosis", "Downslanted palpebral fissures", and "Microtia". In summary, our study demonstrated that the clinical phenotypic spectrum of individual with Mendelian diseases can be characterized through NLP-based digital phenotyping on population-scale electronic health records (EHRs).


Assuntos
Mineração de Dados , Síndrome de Down/patologia , Registros Eletrônicos de Saúde , Fenótipo , Humanos , Processamento de Linguagem Natural
10.
Food Chem ; 358: 129888, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933969

RESUMO

Present study aimed to prepare and identify antioxidative peptides from selenium-containing soybeans, and to investigate their bioavailability and protective effects against oxidative stress-related diseases. Selenium-containing soybean antioxidative peptides (Mw < 1 kDa, SePPs) hydrolyzed by Neutrase and Alcalase reached the highest cellular antioxidant activity (EC50 value 320.5 ± 39.71 µg/L). SePPs could be efficiently absorbed through Caco-2 monolayer, and then significantly reverse the tumor necrosis factor-α (TNF-α)-induced inflammatory cytokine, phosphorylated c-Jun N-terminal kinases (p-JNK) and nuclear factor-kappa B (NF-κB) levels in EA. hy926 cells (p < 0.05). d-galactose-induced aging mice model showed that liver superoxidase dismutase (SOD) and glutathione peroxidase-1 (GPx-1) were enhanced, while aspartate aminotransferase (AST), alanine aminotransferase (ALT) and NF-κB were decreased by SePPs significantly (p < 0.05). SePPs could inhibit brain oxidative stress via regulating MAPK/NF-κB pathway. Comparing with Na2SeO3, selenomethionine (SeMet) and selenium-free peptides, SePPs was found to present synergistic effects of selenium and peptides in antioxidant activity.


Assuntos
Antioxidantes/farmacologia , Peptídeos/farmacologia , Selênio/farmacologia , Proteínas de Soja/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacocinética , Disponibilidade Biológica , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Células CACO-2 , Citocinas/metabolismo , Suplementos Nutricionais , Enzimas/metabolismo , Feminino , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/química , Selênio/química , Selênio/farmacocinética , Proteínas de Soja/química , Fator de Necrose Tumoral alfa/metabolismo
11.
BMC Med Inform Decis Mak ; 20(Suppl 11): 322, 2020 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-33380331

RESUMO

BACKGROUND: Natural language processing (NLP) tools can facilitate the extraction of biomedical concepts from unstructured free texts, such as research articles or clinical notes. The NLP software tools CLAMP, cTAKES, and MetaMap are among the most widely used tools to extract biomedical concept entities. However, their performance in extracting disease-specific terminology from literature has not been compared extensively, especially for complex neuropsychiatric disorders with a diverse set of phenotypic and clinical manifestations. METHODS: We comparatively evaluated these NLP tools using autism spectrum disorder (ASD) as a case study. We collected 827 ASD-related terms based on previous literature as the benchmark list for performance evaluation. Then, we applied CLAMP, cTAKES, and MetaMap on 544 full-text articles and 20,408 abstracts from PubMed to extract ASD-related terms. We evaluated the predictive performance using precision, recall, and F1 score. RESULTS: We found that CLAMP has the best performance in terms of F1 score followed by cTAKES and then MetaMap. Our results show that CLAMP has much higher precision than cTAKES and MetaMap, while cTAKES and MetaMap have higher recall than CLAMP. CONCLUSION: The analysis protocols used in this study can be applied to other neuropsychiatric or neurodevelopmental disorders that lack well-defined terminology sets to describe their phenotypic presentations.


Assuntos
Transtorno do Espectro Autista , Processamento de Linguagem Natural , Benchmarking , Humanos , PubMed , Software
12.
NAR Genom Bioinform ; 2(2): lqaa032, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32500119

RESUMO

Human Phenotype Ontology (HPO) terms are increasingly used in diagnostic settings to aid in the characterization of patient phenotypes. The HPO annotation database is updated frequently and can provide detailed phenotype knowledge on various human diseases, and many HPO terms are now mapped to candidate causal genes with binary relationships. To further improve the genetic diagnosis of rare diseases, we incorporated these HPO annotations, gene-disease databases and gene-gene databases in a probabilistic model to build a novel HPO-driven gene prioritization tool, Phen2Gene. Phen2Gene accesses a database built upon this information called the HPO2Gene Knowledgebase (H2GKB), which provides weighted and ranked gene lists for every HPO term. Phen2Gene is then able to access the H2GKB for patient-specific lists of HPO terms or PhenoPacket descriptions supported by GA4GH (http://phenopackets.org/), calculate a prioritized gene list based on a probabilistic model and output gene-disease relationships with great accuracy. Phen2Gene outperforms existing gene prioritization tools in speed and acts as a real-time phenotype-driven gene prioritization tool to aid the clinical diagnosis of rare undiagnosed diseases. In addition to a command line tool released under the MIT license (https://github.com/WGLab/Phen2Gene), we also developed a web server and web service (https://phen2gene.wglab.org/) for running the tool via web interface or RESTful API queries. Finally, we have curated a large amount of benchmarking data for phenotype-to-gene tools involving 197 patients across 76 scientific articles and 85 patients' de-identified HPO term data from the Children's Hospital of Philadelphia.

13.
Food Res Int ; 131: 108974, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32247485

RESUMO

Two novel calcium delivery systems with high calcium-binding ability were prepared with desalted duck egg white peptides (DPs) and chitosan oligosaccharide (COS) by Amadori-type linkage and transglutaminase (TGase) induced reaction. Fourier transform infrared spectroscopy (FTIR), Zeta potential and particle size analyses were used to characterize the copolymers. These two copolymers reversed the inhibition of phytic acid (PA) in calcium transport in Caco-2 cell monolayers. PA-induced calcium deficiency mice model indicated that copolymers could reverse the side effect of PA, promote calcium bioavailability, and improve gut health. Overall, these results confirmed the potentialities of DPs-COS copolymers as nutraceuticals/functional food for oral calcium delivery to promote calcium absorption and improve gut health.


Assuntos
Cálcio/administração & dosagem , Quitosana/química , Quitosana/metabolismo , Proteínas do Ovo/química , Oligossacarídeos/química , Animais , Transporte Biológico , Células CACO-2 , Liberação Controlada de Fármacos , Patos , Humanos , Masculino , Camundongos , Nanoestruturas , Polímeros/química
14.
J Food Sci ; 85(3): 834-842, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32078745

RESUMO

Osteoporosis is a degenerative disease that threatens bone health of the elderly (especially postmenopausal women). Since osteoporosis is important to prevent, the aim of this study was to investigate the regulation of desalted duck egg white peptides (DPs) on osteoporosis. In this study, the effects of DPs on bone formation were evaluated using MC3T3-E1 cells and ovariectomized (OVX) rats. DPs significantly enhanced the preosteoblasts proliferation, differentiation, and matrix mineralization via the upregulation of wnt3a expression, low-density lipoprotein receptor-related protein-5 (LRP-5), ß-catenin, runt-related transcription factor 2 (Runx2), and osteoprotegerin (OPG) (P < 0.05). The intracellular calcium concentration was significantly elevated by DPs (P < 0.05), which is attributed to calcium influx and L-type calcium channels. Additionally, OVX rat model experiment indicated that DPs (600 mg/kg bw) had a superior effect against bone loss induced by estrogen deficiency, as it significantly declined bone turnover markers, and significantly increased biomechanical parameters (P < 0.05). Mineralized bone surfaces and bone microstructure were also obviously improved by DPs treatment. Immunohistochemical analysis showed that receptor activator of nuclear factor κ B (RANK) expression of tibia in DPs group was significantly reduced compared with the model group (P < 0.05). Our results demonstrated that DPs could enhance preosteoblasts differentiation and antiosteoporosis via wnt/ß-catenin signal pathway and several key osteogenic transcription factors such as Runx2 and OPG. PRACTICAL APPLICATION: High-value utilization of salted duck egg white, a byproduct of food industry, is worthy of in-depth study. Desalted duck egg white peptides (DPs) were proved to promote bone formation, which suggests the potentials of DPs as cofactors in osteoporosis prevention.


Assuntos
Clara de Ovo/química , Osteogênese/efeitos dos fármacos , Osteoporose Pós-Menopausa/tratamento farmacológico , Peptídeos/administração & dosagem , Animais , Osso e Ossos/metabolismo , Cálcio/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Patos , Feminino , Humanos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Camundongos , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/fisiopatologia , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Peptídeos/química , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteína Wnt3/genética , Proteína Wnt3/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
15.
Phytomedicine ; 66: 153130, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31790897

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver diseases. Cyclocarya paliurus (C. paliurus), an edible and medicinal plant in Chinese folk, has been demonstrated to ameliorate diabetes, obesity and lipid metabolism disorders. However, its effects on NAFLD and its potential molecular mechanism have not been clearly expounded. PURPOSE: The present study was designed to explore the therapeutic potential of triterpenic acids-enriched fraction from C. paliurus (CPT), as well as its underlying mechanism in vivo and in vitro models of NAFLD. METHODS: The metabolic effects and possible molecular mechanism of CPT were examined using HepG2 cells and primary hepatocytes (isolated from C57BL/6 J mice) models of fatty liver induced by palmitic acid (PA) and a high fat diet mouse model. RESULTS: In high fat diet-induced C57BL/6 J mice, CPT significantly reduced liver weight index, serum alanine transaminase (ALT), aspartate transaminase (AST), triacylglycerol (TG), total cholesterol (TC) and hepatic TG, TC levels. Moreover, CPT dramatically decreased the contents of blood glucose, insulin, and insulin resistance (HOMA-IR) index. Meanwhile, CPT significantly increased the tyrosine phosphorylation level of IRS and the uptake of 2-deoxyglucose (2DG) in PA-induced HepG2 cells and primary hepatocytes fatty liver models. Furthermore, in PA-induced HepG2 cells and primary hepatocytes, CPT significantly decreased the number of lipid droplets and intracellular TG content. In addition, mechanism investigation showed that CPT increased the phosphorylation of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) and glycogen synthase-3ß (GSK3ß) in vivo and in vitro models, which were abrogated by PI3K inhibitor LY294002 in vitro models. CONCLUSION: These findings indicate that CPT may exert the therapeutic effects on NAFLD via regulating PI3K/Akt/GSK3ß pathway.


Assuntos
Juglandaceae/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Animais , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Glicogênio Sintase Quinase 3 beta/metabolismo , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação , Extratos Vegetais/química , Plantas Medicinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Triglicerídeos/metabolismo , Triterpenos/química
16.
Mol Nutr Food Res ; 63(24): e1900525, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31671239

RESUMO

SCOPE: Val-Ser-Glu-Glu (VSEE), identified from duck egg white peptides, has been proven to facilitate calcium absorption in a previous study. Since prevention of osteoporosis is important, it might act as a potential cofactor in osteoporosis prevention. Therefore, the aim of this study is to investigate the regulation of VSEE on osteoporosis and abnormal lipid metabolisms. METHODS AND RESULTS: MC3T3-E1 cell and ovariectomized (OVX) rat model are used to evaluate VSEE on regulation of bone and lipid metabolisms. Differentiation and matrix mineralization of preosteoblast are significantly increased by VSEE (p <0.05), which attributed to stimulating calcium influx, then to activating Wnt/ß-catenin signaling pathway and regulating runt-related transcription factor 2 and osteoprotegerin. VSEE can cross Caco-2/HT-29 co-cultured monolayer via paracellular pathway and peptide transporter 1 (PepT1), and can be detected in blood and maximum concentration is 122.84 ± 3.68 mg L-1 at 60 min. Additionally, VSEE reverses bone loss and regulate dyslipidemia through Wnt/ß-catenin signaling pathway in OVX rats. Firmicutes phylum, Veillonellaceae, Prevotellaceae and six genera in VSEE group are significantly different compared with the Model group (p < 0.05). CONCLUSION: VSEE promotes bone growth and inhibit abnormal lipid metabolism in an OVX model through the regulation of intestinal microbiota compositions and Wnt/ß-catenin signal pathway.


Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Clara de Ovo/química , Microbioma Gastrointestinal/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Oligopeptídeos/farmacologia , Via de Sinalização Wnt/fisiologia , beta Catenina/fisiologia , Animais , Células CACO-2 , Patos , Feminino , Células HT29 , Humanos , Oligopeptídeos/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoporose Pós-Menopausa/prevenção & controle , Ratos , Ratos Sprague-Dawley , Via de Sinalização Wnt/efeitos dos fármacos
17.
Hum Mutat ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31646703

RESUMO

We recently described a new neurodevelopmental syndrome (TAF1/MRXS33 intellectual disability syndrome) (MIM# 300966) caused by pathogenic variants involving the X-linked gene TAF1, which participates in RNA polymerase II transcription. The initial study reported eleven families, and the syndrome was defined as presenting early in life with hypotonia, facial dysmorphia, and developmental delay that evolved into intellectual disability (ID) and/or autism spectrum disorder (ASD). We have now identified an additional 27 families through a genotype-first approach. Familial segregation analysis, clinical phenotyping, and bioinformatics were capitalized on to assess potential variant pathogenicity, and molecular modelling was performed for those variants falling within structurally characterized domains of TAF1. A novel phenotypic clustering approach was also applied, in which the phenotypes of affected individuals were classified using 51 standardized Human Phenotype Ontology (HPO) terms. Phenotypes associated with TAF1 variants show considerable pleiotropy and clinical variability, but prominent among previously unreported effects were brain morphological abnormalities, seizures, hearing loss, and heart malformations. Our allelic series broadens the phenotypic spectrum of TAF1/MRXS33 intellectual disability syndrome and the range of TAF1 molecular defects in humans. It also illustrates the challenges for determining the pathogenicity of inherited missense variants, particularly for genes mapping to chromosome X. This article is protected by copyright. All rights reserved.

18.
Chemosphere ; 226: 766-773, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30965247

RESUMO

A new reactor of array double dielectric barrier discharge (DDBD) combined with catalysis was prepared, and the effect of different factors on removal efficiency of toluene at pilot scale were investigated. The possible degradation mechanism was explored. The results indicate that the removal efficiency of toluene in the exhaust gas decreases with the increasing of the toluene initial concentration and the gas flow rate, but increases with the increasing of the specific energy density. When the air relative humidity is 55%, the removal efficiency of toluene is higher than that of the relative humidity by 85%. The results of XPS, FT-IR and GC-MS analysis show that the main intermediate products of removing toluene by DDBD combined with TiO2/Al2O3 catalyst are phenol, benzaldehyde, benzyl alcohol, benzoic acid, N-benzyl formamide, dimethyl terephthalate, dimethyl isophthalate and other substances. There are five possible pathways to degrade toluene by DDBD combined with TiO2/Al2O3.


Assuntos
Óxido de Alumínio/química , Eletroquímica/métodos , Titânio/química , Tolueno/isolamento & purificação , Catálise , Gases/análise , Gases em Plasma/análise , Dados Preliminares , Análise Espectral
19.
Biomed Pharmacother ; 104: 229-239, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29775890

RESUMO

The effects of triterpenic acids-enriched fraction from Cyclocarya paliurus (CPT) on nonalcoholic fatty liver disease (NAFLD) were investigated using in vivo and in vitro models. In high fat diet-induced Wister rats, CPT significantly increased superoxide dismutase (SOD) activity and glutathione/oxidized glutathione (GSH/GSSG) ratio, reduced malondialdehyde (MDA) and protein carbonyl (PCO) levels. Moreover, CPT restored mitochondrial membrane potential dysfunction, decreased cytochrome P450 enzyme 2E1 (CYP2E1) activity, improved nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-mediated antioxidant enzyme heme oxygenase1 (HO-1) expression. In free fatty acids-induced HepG2 cells, CPT dramatically decreased ROS content, increased mitochondrial NADH dehydrogenase (Complex I) and mitochondrial cytochrome C oxidase (Complex IV) levels. Furthermore, CPT could upregulate HO-1, quinine oxidoreductase 1 (NQO1) expression, and increase Nrf2 translocation from cytoplasm-to-nucleus. The results indicated CPT could protect mitochondria function and improve oxidative stress by activating Nrf2. Therefore, it can be inferred that CPT may be a potential agent against NAFLD.


Assuntos
Juglandaceae/química , Mitocôndrias/efeitos dos fármacos , Doenças Mitocondriais/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Antioxidantes/metabolismo , Linhagem Celular Tumoral , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Glutationa/metabolismo , Dissulfeto de Glutationa/metabolismo , Heme Oxigenase-1/metabolismo , Células Hep G2 , Humanos , Masculino , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , NADH Desidrogenase/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
20.
Phytochemistry ; 151: 119-127, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29679877

RESUMO

Six undescribed pentacyclic triterpenoids including four triterpenoid aglycones, 1ß,2a,3ß,23-tetrahydroxyurs-12-en-28-ursolic acid, 2a,3a,6ß,19α,23-pentahydroxyurs-12-en-28-ursolic acid, 2α,3α,20ß,23-tetrahydroxyurs-12-en-28-ursolic acid and 1ß,2a,3ß,23-tetrahydroxyurs-12,20(30)-dien-28-ursolic acid, and two triterpenoid glucosides, 2a,3a,23-trihydroxy-12,20(30)-dien-28-ursolic acid 28-O-ß-d-glucopyranoside and 1-oxo-3ß,23-dihydroxyolean-12-en-28-oic acid 28-O-ß-d-xylopyranoside, along with 5 known triterpenoids were isolated from a CH3Cl-soluble extract of the leaves of Cyclocarya paliurus. Their structures were established on the basis of chemical and spectroscopic approaches. These compounds were assessed for their antioxidant effects on FFA-induced hepatic steatosis in HepG2 cells. The results revealed that three saponins and two aglycones markedly increased SOD activity and reduced MDA level.


Assuntos
Antioxidantes/farmacologia , Hepatócitos/efeitos dos fármacos , Juglandaceae/química , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ácidos Graxos não Esterificados , Células Hep G2 , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Conformação Molecular , Estresse Oxidativo/efeitos dos fármacos , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
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