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1.
J Appl Toxicol ; 44(8): 1198-1213, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38639436

RESUMO

Intracerebral hemorrhage (ICH), for which there are currently no effective preventive or treatment methods, has a very high fatality rate. Statins, such as atorvastatin (ATV), are the first-line drugs for regulating blood lipids and treating hyperlipidemia-related cardiovascular diseases. However, ATV-associated ICH has been reported, although its incidence is rare. In this study, we aimed to investigate the protective action and mechanisms of berberine (BBR) against ATV-induced brain hemorrhage. We established an ICH model in zebrafish induced by ATV (2 µM) and demonstrated the effects of BBR (10, 50, and 100 µM) on ICH via protecting the vascular network using hemocyte staining and three transgenic zebrafish. BBR was found to reduce brain inflammation and locomotion injury in ICH-zebrafish. Mechanism research showed that ATV increased the levels of VE-cadherin and occludin proteins but disturbed their localization at the cell membrane by abnormal phosphorylation, which decreased the number of intercellular junctions between vascular endothelial cells (VECs), disrupting the integrity of vascular walls. BBR reversed the effects of ATV by promoting autophagic degradation of phosphorylated VE-cadherin and occludin in ATV-induced VECs examined by co-immunoprecipitation (co-IP). These findings provide crucial insights into understanding the BBR mechanisms involved in the maintenance of vascular integrity and in mitigating adverse reactions to ATV.


Assuntos
Atorvastatina , Berberina , Hemorragia Cerebral , Peixe-Zebra , Animais , Atorvastatina/farmacologia , Hemorragia Cerebral/induzido quimicamente , Berberina/farmacologia , Animais Geneticamente Modificados , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos
2.
Toxicol Appl Pharmacol ; 469: 116529, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37100089

RESUMO

The most commonly reported side effect of azithromycin is gastrointestinal (GI) disorders, and the main acid degradation product is 3'-Decladinosyl azithromycin (impurity J). We aimed to compare the GI toxicity of azithromycin and impurity J on zebrafish larvae and investigate the mechanism causing the differential GI toxicity. Results of our study showed that the GI toxicity induced by impurity J was higher than that of azithromycin in zebrafish larvae, and the effects of impurity J on transcription in the digestive system of zebrafish larvae were significantly stronger than those of azithromycin. Additionally, impurity J exerts stronger cytotoxic effects on GES-1 cells than azithromycin. Simultaneously, impurity J significantly increased ghsrb levels in the zebrafish intestinal tract and ghsr levels in human GES-1 cells compared to azithromycin, and ghsr overexpression significantly reduced cell viability, indicating that GI toxicity induced by azithromycin and impurity J may be correlated with ghsr overexpression induced by the two compounds. Meanwhile, molecular docking analysis showed that the highest -CDOCKER interaction energy scores with the zebrafish GHSRb or human GHSR protein might reflect the effect of azithromycin and impurity J on the expression of zebrafish ghsrb or human ghsr. Thus, our results suggest that impurity J has higher GI toxicity than azithromycin due to its greater ability to elevate ghsrb expression in zebrafish intestinal tract.


Assuntos
Azitromicina , Peixe-Zebra , Animais , Humanos , Azitromicina/toxicidade , Larva , Simulação de Acoplamento Molecular , Intestinos
3.
Crit Rev Food Sci Nutr ; 63(31): 10792-10813, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35748363

RESUMO

Anthocyanins, which are the labile flavonoid pigments widely distributed in many fruits, vegetables, cereal grains, and flowers, are receiving intensive interest for their potential health benefits. Proteins are important food components from abundant sources and present high binding affinity for small dietary compounds, e.g., anthocyanins. Protein-anthocyanin interactions might occur during food processing, ingestion, digestion, and bioutilization, leading to significant changes in the structure and properties of proteins and anthocyanins. Current knowledge of protein-anthocyanin interactions and their contributions to functions and bioactivities of anthocyanin-containing foods were reviewed. Binding characterization of dietary protein-anthocyanins complexes is outlined. Advances in understanding the structure-affinity relationship of dietary protein-anthocyanin interaction are critically discussed. The associated properties of protein-anthocyanin complexes are considered in an evaluation of functional and nutritional values.


Assuntos
Antocianinas , Frutas , Antocianinas/análise , Frutas/química , Verduras/química , Dieta , Proteínas Alimentares/análise
4.
Crit Rev Food Sci Nutr ; : 1-24, 2023 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-37574589

RESUMO

Anthocyanins (ACNs) are one of the subgroups of flavonoids and getting intensive attraction due to the nutritional values. However, their application of ACNs is limited due to their poor stability and bioavailability. Accordingly, nanoencapsulation has been developed to enhance its stability and bio-efficacy. This review focuses on the nano-technique applications of delivery systems that be used for ACNs stabilization, with an emphasis on physicochemical stability and health benefits. ACNs incorporated with delivery systems in forms of nano-particles and fibrils can achieve advanced functions, such as improved stability, enhanced bioavailability, and controlled release. Also, the toxicological evaluation of nano delivery systems is summarized. Additionally, this review summarizes the challenges and suggests the further perspectives for the further application of ACNs delivery systems in food and medical fields.

5.
Crit Rev Food Sci Nutr ; 62(8): 2205-2220, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33256437

RESUMO

Brassicaceae family includes various economic plants for edible or ornamental purposes. Brassicaceae vegetables are considered to be a major part of human diet as sources rich in phytochemicals. Among them, anthocyanins provide red to blue colors in Brassicaceae plants and as well have nutritional value and pharmaceutical potential. This review aims to summarize the chemical composition, stability, bioaccessibility, bioavailability, potential health benefits, and applications of anthocyanins from Brassicaceae. Additionally, the potential for incorporation of Brassicaceae anthocyanins in food systems as food additives and functional ingredients was demonstrated.


Assuntos
Antocianinas , Brassicaceae , Antocianinas/química , Disponibilidade Biológica , Brassicaceae/química , Humanos , Compostos Fitoquímicos/metabolismo , Verduras/química
6.
Biochem Biophys Res Commun ; 534: 950-956, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33143872

RESUMO

Peptide sequence modulates amyloid fibril formation and triggers Alzheimer's disease. The N-terminal region of amyloid peptide is disordered and lack any specific secondary structure. An ionic interaction of Aß1-11 with factor XII is critical for the activation of the contact system in Alzheimer's disease. In this study, we report the self-assembly of fluctuating N-terminal Aß1-11 into nanotubes using atomic force micrography, transmission electron microscopy, circular dichroism studies and molecular modeling studies. The effect of four polyphenols: baicalein, rutin, vanillin and cyanidin-3-O-glucoside (C3G) was also explored on the amyloid fibril inhibitor perspective using amyloid specific dye Thioflavin T (ThT). AFM micrographs suggested the self-assembly of Aß1-11 into nanotubes after three weeks of incubation. Microwave treatment results in the conformational variation of disordered structure to ß-sheet rich amyloid fibrils. The presence of salts (sodium and potassium chloride) induces the structural transformation of Aß1-11 to super-helix. Fluorescence spectroscopy studies using ThT suggested differential inhibition of amyloid fibrils formation in the presence of polyphenols. Molecular modeling studies suggested that binding of polyphenols to Aß1-11 through hydrophobic interaction (Phe4 and Tyr 10) and hydrogen bonding (Glu3 and Arg5) play a substantial role in stabilizing Aß1-11-polyphenols complex. In the presence of polyphenols, Aß1-11 transforms to hybrid nanostructures thus hindering amyloid fibril formation. These results provide structural insights and importance of the N-terminal residues in the Aß1-42 self-assembly mechanism.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Fragmentos de Peptídeos/metabolismo , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/ultraestrutura , Humanos , Modelos Moleculares , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/ultraestrutura , Polifenóis/farmacologia , Estrutura Secundária de Proteína/efeitos dos fármacos
7.
Compr Rev Food Sci Food Saf ; 20(3): 2560-2595, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33786992

RESUMO

Shiitake mushrooms are one of the most popular and highly consumed mushrooms worldwide both in fresh and dry forms. However, it rapidly starts losing its quality immediately after harvest which necessitates processing and/or proper storage before being distributed. However, the processes used for preserving other mushrooms (e.g., Agaricus) become unviable for shiitake due to its uniqueness (higher respiration rate, varied biochemicals, growth, etc.) which demands individual studies on shiitake. This review starts by listing the factors and their interdependence leading to a quality decline in shiitake after harvest. Understanding well about these factors, numerous post-harvest operations preserve shiitake as fresh form for a shorter period and as dried forms for a longer shelf-life. These processes also affect the intrinsic quality and nutrients of shiitake. This review comprehensively summarizes and discusses the effects of chemical processing (washing, fumigation, coating, and ozone), modified atmosphere packaging (including irradiation) on the quality of fresh shiitake while discussing their efficiency in extending their shelf-life by inhibiting microbial spoilage and deterioration in quality including texture, appearance, nutrients, and favor. It also reviews the impact of thermal dehydration on the quality of dried shiitake mushrooms, especially the acquired unique textural, nutritional, and aromatic properties along with their merits and limitations. Since shiitake are preferred to be low-cost consumer products, the applicability of freeze-drying and sophisticated novel methodologies, which prove to be expensive and/or complex, are discussed. The review also outlines the challenges and proposes the subsequent future directives, which either retains/enhances the desirable quality in shiitake mushrooms.


Assuntos
Agaricales , Cogumelos Shiitake , Atmosfera , Desidratação , Fumigação , Humanos
8.
Mol Phylogenet Evol ; 148: 106809, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32224125

RESUMO

The grape genus (Vitis L.) is of great agronomic importance and represents an economically valuable resource. Researchers have explored the phylogenetic relationships of subgenus Vitis for decades. However, the evolutionary patterns of many morphological characters of subgenus Vitis have not yet been explored in the context of a robust phylogenetic framework. Within the East Asian clade, V. bryoniifolia and its closely related taxa form the V. bryoniifolia clade, which is taxonomically complex. The phylogenetic relationships and species delimitation within this clade remain poorly resolved, due to the limited sampling in prior studies. We tested morphological trait evolution based on ancestral character state reconstruction using a phylogenomic framework. With 89 accessions from the East Asian subgenus Vitis sampled, a robust phylogenetic relationship of the V. bryoniifolia clade is reconstructed using the restriction-site associated DNA sequencing (RAD-seq) data, which support the monophyly of most taxa of the V. bryoniifolia clade. Ancestral character state reconstructions suggest that the weak climbing ability and simplified tendrils of Vitis each evolved multiple times. This study provides a reliable phylogenomic framework for the V. bryoniifolia clade. Coupled with morphological analyses, we discuss the taxonomic status of some taxa in the V. bryoniifolia clade and untangle a taxonomic dilemma in the grape genus.


Assuntos
Filogenia , Característica Quantitativa Herdável , Vitis/anatomia & histologia , Vitis/classificação , Sequência de Bases , Funções Verossimilhança , Fenótipo , Folhas de Planta/anatomia & histologia , Análise de Componente Principal , Análise de Sequência de DNA , Especificidade da Espécie
9.
Int J Mol Sci ; 21(21)2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33147881

RESUMO

Accumulation of amyloid fibrils in organisms accompanies many diseases. Natural extracts offer an alternative strategy to control the process with potentially fewer side effects. In this study, the inhibition of C-phycocyanin from Spirulina sp. on amyloid formation of bovine serum albumin (BSA) during a 21-day incubation was investigated using fluorescence and circular dichroism (CD), and mechanisms were explored via kinetic fitting and molecular docking. C-phycocyanin (0-50 µg/mL) hindered the amyloid formation process of BSA with increased half-lives (12.43-17.73 days) based on fluorescence intensity. A kinetic model was built and showed that the k1 decreased from 1.820 × 10-2 d-1 to 2.62 × 10-3 d-1 with the increase of C-phycocyanin, while k2 showed no changes, indicating that the inhibition of BSA fibrillation by C-phycocyanin occurred in a spontaneous process instead of self-catalyzed one. CD results show that C-phycocyanin inhibited conformational conversion (α-helices and ß-sheets) of BSA from day 6 to day 18. Molecular docking suggested that C-phycocyanin may hinder BSA fibrillation by hydrogen-bonding > 6 of 27 α-helices of BSA in a gomphosis-like structure, but the unblocked BSA α-helices might follow the self-catalytic process subsequently.


Assuntos
Amiloide/antagonistas & inibidores , Amiloide/química , Cianobactérias/química , Ficocianina/química , Soroalbumina Bovina/química , Animais , Benzotiazóis/química , Catálise , Bovinos , Dicroísmo Circular , Ligação de Hidrogênio , Cinética , Microscopia de Fluorescência , Simulação de Acoplamento Molecular , Pigmentação , Ligação Proteica , Estrutura Secundária de Proteína , Spirulina/química
10.
Physiol Plant ; 166(2): 478-493, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30216458

RESUMO

Wintersweet (Chimonanthus praecox L.) is an important ornamental plant in China with a pleasant floral scent. To explore the potential mechanisms underlying differences in the fragrances among genotypes of this plant, we analyzed floral volatile organic compounds (VOCs) from two different genotypes: SW001, which has little to no fragrance, and the scented genotype H29. The major VOCs in H29 were linalool, trans-ß-ocimene, benzyl acetate, methyl salicylate, benzyl alcohol (BAlc) and methyl benzoate. The most important aroma-active compound in H29, linalool, was emitted at a low concentration in SW001, which had markedly higher levels of trans-ß-ocimene than H29. Next, to investigate scent biosynthesis, we analyzed the transcriptome and proteome of fully open flowers of the two genotypes. A total of 14 443 differentially expressed unigenes and 196 differentially expressed proteins were identified. Further analyses indicated that 56 differentially expressed genes involved in the terpenoid and benzenoid biosynthesis pathways might play critical roles in regulating floral fragrance difference. Disequilibrium expression of four terpene synthase genes resulted in diverse emission of linalool and trans-ß-ocimene in both genotypes. In addition, the expressions of two CpMYC2 transcription factors were both upregulated in H29, implying that they may regulate linalool production. Notably, 16 of 20 genes in the benzenoid biosynthesis pathway were downregulated, corresponding to the relatively low level of benzenoid production in SW001. The lack of benzyl acetate might indicate that SW001 may lack substrate BAlc or functional acetyl-CoA:benzylalcohol acetyltransferase.


Assuntos
Calycanthaceae/genética , Calycanthaceae/metabolismo , Flores/genética , Flores/metabolismo , Proteômica/métodos , Transcriptoma/genética , Monoterpenos Acíclicos , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Regulação da Expressão Gênica de Plantas , Monoterpenos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Terpenos/metabolismo , Compostos Orgânicos Voláteis/metabolismo
11.
J Biol Chem ; 292(44): 18062-18074, 2017 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-28928221

RESUMO

Parkinson's disease (PD) is one of the most epidemic neurodegenerative diseases and is characterized by movement disorders arising from loss of midbrain dopaminergic (DA) neurons. Recently, the relationship between PD and autophagy has received considerable attention, but information about the mechanisms involved is lacking. Here, we report that autophagy-related gene 5 (ATG5) is potentially important in protecting dopaminergic neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in zebrafish. Using analyses of zebrafish swimming behavior, in situ hybridization, immunofluorescence, and expressions of genes and proteins related to PD and autophagy, we found that the ATG5 expression level was decreased and autophagy flux was blocked in this model. The ATG5 down-regulation led to the upgrade of PD-associated proteins, such as ß-synuclein, Parkin, and PINK1, aggravation of MPTP-induced PD-mimicking pathological locomotor behavior, DA neuron loss labeled by tyrosine hydroxylase (TH) or dopamine transporter (DAT), and blocked autophagy flux in the zebrafish model. ATG5 overexpression alleviated or reversed these PD pathological features, rescued DA neuron cells as indicated by elevated TH/DAT levels, and restored autophagy flux. The role of ATG5 in protecting DA neurons was confirmed by expression of the human atg5 gene in the zebrafish model. Our findings reveal that ATG5 has a role in neuroprotection, and up-regulation of ATG5 may serve as a goal in the development of drugs for PD prevention and management.


Assuntos
Proteína 5 Relacionada à Autofagia/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Regulação da Expressão Gênica , Terapia Genética , Transtornos Parkinsonianos/prevenção & controle , Proteínas de Peixe-Zebra/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Autofagia/efeitos dos fármacos , Proteína 5 Relacionada à Autofagia/antagonistas & inibidores , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Biomarcadores/metabolismo , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/patologia , Linhagem Celular Tumoral , DNA Recombinante/uso terapêutico , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/patologia , Embrião não Mamífero , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Larva , Microinjeções , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/uso terapêutico , Neuroproteção/efeitos dos fármacos , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia , Peixe-Zebra , Proteínas de Peixe-Zebra/antagonistas & inibidores , Proteínas de Peixe-Zebra/genética
12.
Arch Biochem Biophys ; 643: 50-56, 2018 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-29475050

RESUMO

In this study, chemical chaperone like function of cyanidin-3-O-glucoside (C3G) was investigated through fluorescence spectroscopy, UV-visible spectroscopy, circular dichroism spectroscopy, confocal microscopy, scanning electron microscopy and molecular docking studies. Early and advanced glycation inhibitory effect was evaluated by fluorescence spectroscopy and agarose gel electrophoresis. Amyloids were investigated based on their propensity to bind Congo Red (CR) and Thioflavin T (ThT) by multiple microscopic approaches. Circular dichroism studies were used to analyze the changes in the secondary structure due to glycation. C3G effectively inhibited early and advanced glycation by masking like function, carbonyl scavenging and chemical chaperone activity. C3G had molecular interaction with Glu186, Arg427, Ser428, Lys431, Arg435, and Arg458 of BSA. Based on the microscopic analysis, it is evident that C3G can inhibit protein aggregation and amyloid formation. Circular dichroism studies suggested that glycation had resulted in augmented ß-sheet propensity, whereas C3G had a protective effect on the helical conformation of BSA. We conclude that C3G has a chemical chaperone like function on the event of glycation mediated amyloid formation in BSA.


Assuntos
Proteínas Amiloidogênicas/química , Antocianinas/farmacologia , Glucosídeos/farmacologia , Soroalbumina Bovina/química , Proteínas Amiloidogênicas/metabolismo , Animais , Antocianinas/metabolismo , Bovinos , Glucosídeos/metabolismo , Glicosilação/efeitos dos fármacos , Simulação de Acoplamento Molecular , Agregados Proteicos/efeitos dos fármacos , Estrutura Secundária de Proteína/efeitos dos fármacos , Soroalbumina Bovina/metabolismo , Solubilidade
13.
Clin Chem Lab Med ; 55(2): 284-298, 2017 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-27394044

RESUMO

BACKGROUND: Although several studies have explored the genetic polymorphisms of apolipoprotein E (APOE) and their impact on premature coronary artery disease (PCAD), there is still some controversy regarding the significance of their association. Our aim is to estimate the association between APOE polymorphisms and PCAD via meta-analysis. METHODS: All relevant case-control studies and cohort studies published in Chinese or English prior to March 2016 were searched for in electronic databases. Detailed information concerning each piece of literature was independently extracted by two researchers. We used STATA11.0 to process all data and to determine the pooled odds ratio (OR). Altogether, four genetic models were applied to calculate OR and 95% confidence interval (CI): (1) ε2 allele vs. ε3 allele; (2) ε2 carriers vs. ε3/3; (3) ε4 allele vs. ε3 allele; (4) ε4 carriers vs. ε3/3. RESULTS: Eighteen studies concerning APOE polymorphisms and their impact on PCAD were included in the final analysis. The pooled analysis displayed that the ε2 allele and ε2 carriers increased the risk of PCAD significantly among Asians (OR 1.54; 95% CI, 1.09-2.17; OR 1.65; 1.10-2.47), while they showed protective effects on PCAD in Caucasians (OR 0.77; 95% CI, 0.62-0.95; OR 0.69; 0.54-0.89). Subjects with the ε4 allele and ε4 carriers showed significant associations with PCAD (OR 1.62; 95% CI, 1.27-2.06; OR 1.65; 1.27-2.15). CONCLUSIONS: Our investigation supported the fact that the ε2 allele in APOE may appear as a risk factor for PCAD in Asians while a protective factor in Caucasians and that the ε4 allele acted as a genetic risk factor for PCAD.


Assuntos
Apolipoproteínas E/genética , Doença da Artéria Coronariana/genética , Polimorfismo Genético/genética , Adulto , Alelos , Doença da Artéria Coronariana/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Yao Xue Xue Bao ; 51(4): 580-7, 2016 04.
Artigo em Zh | MEDLINE | ID: mdl-29859527

RESUMO

Epilepsy is a kind of neurogenic diseases with high prevalence and characterized by seizure, brain paradoxical discharge and convulsion in spontaneous, transient, recurrent and uncontrolled manner. Development of new anti-epilepsy drugs requires a new reliable and high-performance animal models in screening of leading compounds. In this study, an epilepsy model in larval zebrafish was established using pentylenetetrazole (PTZ) compound. The results show that PTZ induced epilepsy-like seizure behavior such as irregular circular swimming, exciting locomotion, high swim velocity and convulsion in zebrafish. Expression patterns of two epilepsy-related gene c-fos and lgi1 were analyzed using RT-PCR and in situ hybridization; c-fos was enhanced and extended and lgi1 expression was reduced in PTZ concentration-dependent in the larval brain. When the model larvae exposed to anticonvulsant valproate(VPA), the epilepsy-like symptom decreased or disappeared, the marker genes c-fos and lgi1, as well as NeuN protein recovered to the normal levels. These responses to PTZ and to antiepileptic drug VPA are consistent with the observations in clinical studies and mouse models. Using this model, we evaluated anti-epilepsy activity of compounds Y53 and BMT, two homolog of berberine. The results show that the model larvae seizure triggered by lighting was partly remedied by Y53; and the larval exciting locomotion under the condition of no stimulation was suppressed by BMT. The findings indicate that the zebrafish larval epilepsy model is able to distinguish compounds with different activities in eleptiform seizure. We conclude that the zebrafish epilepsy model may be as a reliable and useful platform in screening of new anti-epilepsy candidates, which is suitable for basic research in epilepsy pathogenesis.


Assuntos
Modelos Animais de Doenças , Epilepsia/fisiopatologia , Convulsões/fisiopatologia , Peixe-Zebra , Animais , Anticonvulsivantes , Encéfalo/metabolismo , Epilepsia/induzido quimicamente , Larva , Proteínas do Tecido Nervoso/metabolismo , Pentilenotetrazol , Proteínas Proto-Oncogênicas c-fos/metabolismo , Convulsões/induzido quimicamente , Natação , Ácido Valproico , Proteínas de Peixe-Zebra/metabolismo
15.
J Appl Toxicol ; 35(3): 241-52, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24853142

RESUMO

Drug-induced cardiotoxicity is a leading factor for drug withdrawals, and limits drug efficacy and clinical use. Therefore, new alternative animal models and methods for drug safety evaluation have been given great attention. Anthracyclines (ANTs) are widely prescribed anticancer agents that have a cumulative dose relationship with cardiotoxicity. We performed experiments to study the toxicity of ANTs in early developing zebrafish embryos, especially their effects on the heart. LC50 values for daunorubicin, pirarubicin, doxorubicin (DOX), epirubicin and DOX-liposome at 72 h post-fertilization were 122.7 µM, 111.9 µM, 31.2 µM, 108.3 µM and 55.8 µM, respectively. At the same time, zebrafish embryos were exposed to ANTs in three exposure stages and induced incomplete looping of the heart tube, pericardia edema and bradycardia in a dose-dependent manner, eventually leading to death. DOX caused the greatest heart defects in the treatment stages and its liposome reduced the effects on the heart, while daunorubicin produced the least toxicity. Genes and proteins related to heart development were also identified to be sensitive to ANT exposure and downregulated by ANTs. It revealed ANTs could disturb the heart formation and development. ANTs induced cardiotoxicity in zebrafish has similar effects in mammalian models, indicating that zebrafish may have a potential value for assessment of drug-induced developmental cardiotoxicity.


Assuntos
Antraciclinas/toxicidade , Antineoplásicos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Cardiopatias Congênitas/induzido quimicamente , Peixe-Zebra , Animais , Cardiotoxicidade , Relação Dose-Resposta a Droga , Embrião não Mamífero/patologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Peixe-Zebra/embriologia
16.
J Stroke Cerebrovasc Dis ; 24(12): 2728-37, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26342996

RESUMO

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) increase future intracerebral hemorrhage (ICH) risk after ischemic stroke (IS) or transient ischemic attack (TIA). However, whether CMB-related ICH risk depends on CMB quantity, CMB location, or antithrombotic agents is unclear. We performed a systematic review and meta-analysis to investigate CMB-related ICH risk, stratifying patients according to the quantity of CMB, the location of CMB, and the type of antithrombotic therapy used. METHODS: Literature databases were searched for prospective cohorts reporting ICH outcomes in patients with IS or TIA with baseline CMB evaluation. We calculated pooled relative ratios (RRs) for ICH among patients with and without CMBs. Pooled RRs of CMB-related ICH were further calculated in subgroups stratified by CMB quantity, CMB location, and antithrombotic therapy. RESULTS: Among the 10 included studies, the pooled RR of future ICH was 7.73 (95% confidence interval [CI], 4.07-14.70; P < .001) in CMB versus non-CMB patients. Subgroup analysis revealed that compared with non-CMB patients, multiple-CMB patients were at an increased risk for future ICH (RR = 8.02; 95% CI, 3.21-20.01; P < .001), whereas single-CMB patients did not incur this risk (RR = 2.33; 95% CI, .63-8.63; P = .205). A strong association was found between CMB presence and subsequent ICH in antiplatelet users (RR = 16.56; 95% CI, 3.68-74.42; P < .001). Studies on CMB-related ICH according to CMB locations and in anticoagulant users are lacking for subgroup analysis. CONCLUSION: Our study revealed that patients with IS or TIA with multiple CMBs may incur a higher risk of future ICH, and the presence of CMBs in patients with IS or TIA using antiplatelet agents may significantly increase the subsequent ICH risk.


Assuntos
Hemorragias Intracranianas/etiologia , Ataque Isquêmico Transitório/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Humanos , Ataque Isquêmico Transitório/complicações , Inibidores da Agregação Plaquetária/uso terapêutico , Recidiva , Fatores de Risco , Acidente Vascular Cerebral/complicações , Resultado do Tratamento
17.
Molecules ; 19(7): 9675-88, 2014 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-25004074

RESUMO

Red radish (Raphanus L.) pickles are popular appetizers or spices in Asian-style cuisine. However, tons of radish brines are generated as wastes from industrial radish pickle production. In this study, we evaluated the dynamic changes in colour properties, phenolics, anthocyanin profiles, phenolic acid composition, flavonoids, and antioxidant properties in radish brines during lactic acid fermentation. The results showed that five flavonoids detected were four anthocyanins and one kaempferol derivative, including pelargonidin-3-digluoside-5-glucoside derivatives acylated with p-coumaric acid, ferulic acid, p-coumaric and manolic acids, or ferulic and malonic acids. Amounts ranged from 15.5-19.3 µg/mL in total monomeric anthocyanins, and kaempferol-3,7-diglycoside (15-30 µg/mL). 4-Hydroxy-benzoic, gentisic, vanillic, syringic, p-coumaric, ferulic, sinapic and salicylic acids were detected in amounts that varied from 70.2-92.2 µg/mL, whereas the total phenolic content was 206-220 µg/mL. The change in colour of the brine was associated with the accumulation of lactic acid and anthocyanins. The ORAC and Fe2+ chelation capacity of radish brines generally decreased, whereas the reducing power measured as FRAP values was increased during the fermentation from day 5 to day 14. This study provided information on the phytochemicals and the antioxidative activities of red radish fermentation waste that might lead to further utilization as nutraceuticals or natural colorants.


Assuntos
Antioxidantes/química , Fermentação , Ácido Láctico/química , Compostos Fitoquímicos/química , Raphanus/química , Sais/química , Antocianinas , Antioxidantes/farmacologia , Flavonoides , Concentração de Íons de Hidrogênio , Hidroxibenzoatos , Fenóis , Compostos Fitoquímicos/farmacologia , Pigmentos Biológicos/química , Sais/farmacologia
18.
Yao Xue Xue Bao ; 49(6): 843-8, 2014 Jun.
Artigo em Zh | MEDLINE | ID: mdl-25212030

RESUMO

To investigate vincristine-induced dopaminergic neurons toxicity and mechanism, and explore the molecular target to reduce the toxicity, zebrafish was chosen as a model animal, based on RT-PCR, Western blotting, whole mount in situ immunofluorescence and other technical means. The results showed that the transcription levels of tyrosine hydroxylase gene and dopamine transporter protein gene were inhibited. Furthermore, the number of dopaminergic neurons was decreased by vincristine. Autophagy was suppressed and beclin1 gene expression was inhibited in a dose-dependent manner by vincristine in larval zebrafish. Up-regulated beclin1 partly reduced vincristine-induced neurotoxicity, and down-regulated beclin1 increased toxicity. Beclin1 plays an important role in vincristine-induced dopaminergic neurons toxicity.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Vincristina/efeitos adversos , Proteínas de Peixe-Zebra/metabolismo , Animais , Autofagia , Neurônios Dopaminérgicos/patologia , Relação Dose-Resposta a Droga , Regulação para Baixo , Regulação da Expressão Gênica/efeitos dos fármacos , Larva/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismo , Peixe-Zebra
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(5): 1312-8, 2014 May.
Artigo em Zh | MEDLINE | ID: mdl-25095429

RESUMO

In the present study, the MODIS data were used to monitor the situation of Ulva prolifera in the Shandong Peninsula waters during the period of 2008-2012. Those studies mainly calculate the area of NDVI, and get the information of the time, area , scope , floating path of Ulva prolifera by using threshold segmentation method. The feasibility of monitoring Ulva prolifera information based on MODIS data and the macroscopic regularity of the outburst of Ulva prolifera was elementally studied. The results showed that Ulva prolifera first generated in the middle of May or early June, the time, area, scope of Ulva prolifera reached a maximum, but the relative crowding density was earlier or later when Ulva prolifera developed into a outburst. Finally, Ulva prolifera died away after existing for 71 days in the late July or the early August. Wholly, the floating path moved to the northwest from off the coast to offshore. Based on those aspects above, the outburst of Ulva prolifera in 2008 and 2009 was more serious than others.


Assuntos
Eutrofização , Ulva/crescimento & desenvolvimento , China , Imagens de Satélites
20.
Food Chem ; 450: 139348, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38615533

RESUMO

Poor dispersion stability of nutritious rice bran milk limits its production. In this study, the dispersion stability of rice bran milk after heating at 95 °C for 0-5 min was investigated. Visual observation revealed improved dispersion stability and changes in settling behavior with heat durations. After heating for 5 min, the serum turbidity increased from 1.86 to 2.95. The centrifugal sedimentation rate unexpectedly rose from 9.25% to 29.18%, indicating an increase in volumetric particle concentration. Fourier transform infrared spectroscopy revealed that heating induced starch gelatinization and protein denaturation in rice bran milk, leading to increased volumetric particle concentration. Rice bran protein aggregates after heating were developed and embedded in the gel-like network composed of swollen starch granules. These results suggested that rice bran milk, due to thermal-induced alteration in biomacromolecules, may behave progressively from free settling to hindered settling to compression settling, resulting in improved dispersion stability.


Assuntos
Temperatura Alta , Oryza , Oryza/química , Manipulação de Alimentos , Tamanho da Partícula , Amido/química , Animais
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