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1.
Sci Rep ; 14(1): 308, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172290

RESUMO

Alzheimer's disease (AD) is considered the leading cause of dementia in the elderly worldwide. It results in progressive memory loss and impairment of cognitive and motor skills, leading to a high degree of disability and dependence. The development of AD is associated with the accumulation of senile plaques in the brain, caused by the amyloidogenic pathway of the disease. Several genetic and biochemical events are linked to AD development, with oxidative stress being one of them. Due to the scarcity of drugs aimed at treating AD, antioxidant compounds are increasingly studied as therapeutic targets for the disease. In this study, we investigate the antioxidant and anti-Alzheimer potential of the Tetragonisca angustula (Jataí) pollen extract in a Drosophila melanogaster Alzheimer's model. For this purpose, we utilized a D. melanogaster AD-like model, which expresses genes related to the amyloidogenic pathway of Alzheimer's disease. We explored the floral origin of the collected pollen, conducted phytochemical prospecting, and evaluated its antioxidant capacity in vitro. In vivo experiments involved assessing the survival and climbing ability of the D. melanogaster AD-like model with various concentrations of the pollen extract. Our findings revealed that the pollen extract of Tetragonisca angustula exhibits a significant antioxidant response and high concentrations of important phytochemicals, such as flavonoids and polyphenols. Furthermore, it enhanced the survival rate of D. melanogaster, and across all concentrations tested, it improved the climbing ability of the flies after 15 days of treatment with methanolic pollen extract. Additionally, the pollen extract reduced the neurodegeneration index in histopathological analysis. Thus, our study demonstrates the potential of Tetragonisca angustula pollen as an important subject for further investigation, aiming to isolate molecules that could potentially serve as therapeutic targets for Alzheimer's disease.


Assuntos
Doença de Alzheimer , Antioxidantes , Humanos , Abelhas , Animais , Idoso , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Doença de Alzheimer/metabolismo , Drosophila melanogaster , Pólen/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
2.
PLoS One ; 18(9): e0291242, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37768921

RESUMO

This study addresses the current trend of essential oils in alternative medicine using the non-chordate model Drosophila melanogaster. Following the three R's principles, it proposes non-chordate models to fill knowledge gaps on essential oil toxicity. Copaiba, lavender, and ginger essential oils are evaluated for effects on D. melanogaster lifespan, climbing ability, and brain structure, while their anti-inflammatory properties are also analyzed. Results show dose-related differences: higher concentrations (0.25% v/v) cause brain deterioration and impaired climbing, while lower concentrations (0.0625% v/v for copaiba and ginger; 0.125% for lavender) have no effect on climbing or brain structure. Lavender oil significantly extends lifespan and maintains anti-inflammatory activity when ingested, underscoring its therapeutic potential. These findings highlight the importance of D. melanogaster as a model for studying essential oil properties, potentially replacing chordate models. In addition, this research advances alternative remedies for currently incurable diseases, with lavender oil emerging as a promising candidate for drug discovery.


Assuntos
Cordados , Lavandula , Óleos Voláteis , Animais , Drosophila melanogaster , Lavandula/química , Óleos Voláteis/toxicidade , Óleos Voláteis/química , Óleos de Plantas/toxicidade , Óleos de Plantas/química , Encéfalo
3.
Sci Rep ; 12(1): 11065, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35773306

RESUMO

Alzheimer's disease (AD) is the most common form of dementia in the elderly, affecting cognitive, intellectual, and motor functions. Different hypotheses explain AD's mechanism, such as the amyloidogenic hypothesis. Moreover, this disease is multifactorial, and several studies have shown that gut dysbiosis and oxidative stress influence its pathogenesis. Knowing that kefir is a probiotic used in therapies to restore dysbiosis and that the bioactive peptides present in it have antioxidant properties, we explored its biotechnological potential as a source of molecules capable of modulating the amyloidogenic pathway and reducing oxidative stress, contributing to the treatment of AD. For that, we used Drosophila melanogaster model for AD (AD-like flies). Identification of bioactive peptides in the kefir sample was made by proteomic and peptidomic analyses, followed by in vitro evaluation of antioxidant and acetylcholinesterase inhibition potential. Flies were treated and their motor performance, brain morphology, and oxidative stress evaluated. Finally, we performed molecular docking between the peptides found and the main pathology-related proteins in the flies. The results showed that the fraction with the higher peptide concentration was positive for the parameters evaluated. In conclusion, these results revealed these kefir peptide-rich fractions have therapeutic potential for AD.


Assuntos
Doença de Alzheimer , Kefir , Acetilcolinesterase/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Antioxidantes/análise , Brasil , Drosophila melanogaster/metabolismo , Disbiose , Simulação de Acoplamento Molecular , Peptídeos/química , Proteômica
4.
Sci Rep ; 11(1): 11262, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34045626

RESUMO

Alzheimer's Disease (AD) is the most common cause of dementia among elderly individuals worldwide, leading to a strong motor-cognitive decline and consequent emotional distress and codependence. It is traditionally characterized by amyloidogenic pathway formation of senile plaques, and recent studies indicate that dysbiosis is also an important factor in AD's pathology. To overcome dysbiosis, probiotics-as kefir-have shown to be a great therapeutic alternative for Alzheimer's disease. In this present work, we explored kefir as a probiotic and a metabolite source as a modulator of microbiome and amyloidogenic pathway, using a Drosophila melanogaster model for AD (AD-like flies). Kefir microbiota composition was determined through 16S rRNA sequencing, and the metabolome of each fraction (hexane, dichloromethane, ethyl acetate, and n-butanol) was investigated. After treatment, flies had their survival, climbing ability, and vacuolar lesions accessed. Kefir and fraction treated flies improved their climbing ability survival rate and neurodegeneration index. In conclusion, we show that kefir in natura, as well as its fractions may be promising therapeutic source against AD, modulating amyloidogenic related pathways.


Assuntos
Doença de Alzheimer/metabolismo , Comportamento Animal/fisiologia , Kefir , Probióticos , Animais , Modelos Animais de Doenças , Drosophila melanogaster , Metaboloma , Microbiota , Taxa de Sobrevida
5.
Sci Rep ; 11(1): 9882, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972627

RESUMO

In bees from genus Melipona, differential feeding is not enough to fully explain female polyphenism. In these bees, there is a hypothesis that in addition to the environmental component (food), a genetic component is also involved in caste differentiation. This mechanism has not yet been fully elucidated and may involve epigenetic and metabolic regulation. Here, we verified that the genes encoding histone deacetylases HDAC1 and HDAC4 and histone acetyltransferase KAT2A were expressed at all stages of Melipona scutellaris, with fluctuations between developmental stages and castes. In larvae, the HDAC genes showed the same profile of Juvenile Hormone titers-previous reported-whereas the HAT gene exhibited the opposite profile. We also investigated the larvae and larval food metabolomes, but we did not identify the putative queen-fate inducing compounds, geraniol and 10-hydroxy-2E-decenoic acid (10HDA). Finally, we demonstrated that the histone deacetylase inhibitor 10HDA-the major lipid component of royal jelly and hence a putative regulator of honeybee caste differentiation-was unable to promote differentiation in queens in Melipona scutellaris. Our results suggest that epigenetic and hormonal regulations may act synergistically to drive caste differentiation in Melipona and that 10HDA is not a caste-differentiation factor in Melipona scutellaris.


Assuntos
Abelhas/fisiologia , Comportamento Alimentar/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Hierarquia Social , Monoterpenos Acíclicos/metabolismo , Animais , Epigênese Genética , Ácidos Graxos/metabolismo , Ácidos Graxos Monoinsaturados/metabolismo , Feminino , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Proteínas de Insetos/antagonistas & inibidores , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Hormônios Juvenis/metabolismo
6.
J Psychiatr Res ; 111: 110-120, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30716647

RESUMO

Changes in microRNAs (miRNAs) expression have been described in major depressive disorder in young and middle-aged adults. However, no study has evaluated miRNA expression in older adults with major depression (or late-life depression [LLD]). Our primary aim was to evaluate the expression of miRNAs in subjects with LLD. We first evaluated the miRNA expression using next-generation sequencing (NGS) and then we validated the miRNAs found in NGS in an independent sample of LLD patients, using RT-qPCR. Drosophila melanogaster model was used to evaluate the impact of changes in miRNA expression on behavior. NGS analysis showed that hsa-miR-184 (log2foldchange = -4.21, p = 1.2 × 10-03) and hsa-miR-1-3p (log2foldchange = -3.45, p = 1.3 × 10-02) were significantly downregulated in LLD compared to the control group. RT-qPCR validated the downregulation of hsa-miR-184 (p < 0.001), but not for the hsa-miR-1-3p. The knockout flies of the ortholog of hsa-miR-184 showed significantly reduced locomotor activity at 21-24 d.p.e (p = 0.04) and worse memory retention at 21-24 d.p.e (24h post-stimulus, p = 0.02) compared to control flies. Our results demonstrated that subjects with LLD have significant downregulation of hsa-miR-184. Moreover, the knockout of hsa-miR-184 in flies lead to depressive-like behaviors, being more pronounce in older flies.


Assuntos
Envelhecimento/genética , Comportamento Animal , Disfunção Cognitiva/genética , Transtorno Depressivo Maior/genética , Locomoção , MicroRNAs/genética , Retenção Psicológica , Fatores Etários , Idoso , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Regulação para Baixo , Proteínas de Drosophila , Drosophila melanogaster , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Locomoção/genética , Masculino , Pessoa de Meia-Idade , Análise de Sequência de RNA , Pesquisa Translacional Biomédica
7.
Environ Sci Pollut Res Int ; 25(24): 24084-24092, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29948684

RESUMO

Birds have often played an important role as environmental bioindicators, and different species can be useful due to their bioaccumulating capacity. The micronuclei test is a cytologic technique used for accessing DNA and is a biomarker for damage to DNA. This study analysed the Cerrado avian community, especially the efficiency of the blue-black grassquit (Volatinia jacarina) in responding to pesticide contamination in situ on different-sized coffee farms in southeast Brazil. The micronuclei test was used in erythrocytes of birds. Eighty-two individuals of 21 bird species belonging to 11 families that were found in all study areas were used to evaluate micronuclei (MN) frequency. Two hundred fifty-two MN were counted in every area of study. The MN average count was 3/10,000 erythrocytes, and 17.1% of all bird species exhibited no MN. The average MN was 1.29 ± 0.69 in small farms, 2.59 ± 1.65 in medium farms, and 5.41 ± 1.34 in large farms. Small farms accounted for 14.3% of MN frequency, medium farms 27.8%, and large farms 57.9%. V. jacarina was the most abundant species found and displayed a sensitive response to environmental contamination. Pesticides appear to induce MN formation in a dose-dependent way when farms are analysed according to their area. Therefore, biomonitoring birds remain an efficient means to detect environmental pollutants, especially pesticides. V. jacarina responds as a sensitive biomonitor, showing a dose-dependent response to pesticides used in coffee farms.


Assuntos
Aves , Monitoramento Ambiental/métodos , Poluentes Ambientais/toxicidade , Testes para Micronúcleos/métodos , Praguicidas/toxicidade , Animais , Brasil , Coffea , Ecotoxicologia/métodos , Biomarcadores Ambientais , Eritrócitos , Fazendas , Passeriformes
8.
Biosci. j. (Online) ; 32(4): 1025-1039, july/aug. 2016. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-965641

RESUMO

Soft drinks are industrialized unfermented beverages, free of alcohol, carbonated, rich in artificial flavors and sugar. The intense consumption of such beverages can be related to not inheritable diseases such as caries, allergy, cellulite and stretch marks, gastrointestinal disorders, diabetes and cancer. The aim of this study was to evaluate the carcinogenic potential of different concentrations of soft drinks produced in the Uberlândia city, Minas Gerais State, Brazil, by means of Epithelial Tumor Detection Test using Drosophila melanogaster as a model. Third stage larvae descendants of crosses between D. melanogaster virgin females wts/TM3, sb¹ and males mwh/mwh were treated with different concentrations (0.83, 1.66 or 3.33 mL/g) of cola, diet cola, orange or lemon soft drinks. The total epithelial tumor rate observed in flies treated with 3.33 mL/g of cola and orange soft drinks was higher than the negative control. The diet cola and lemon caused no significant increase in the overall frequency of epithelial tumors in D. melanogaster. In conclusion, in these experimental conditions, the cola and orange base soft drinks demonstrated carcinogenic potential in somatic cells of D. melanogaster in the concentration of 3.33 mL/g.


Refrigerantes são bebidas industrializadas não fermentadas, livre de álcool, carbonatadas, ricas em aromas artificiais e açúcar. O consumo intenso dessas bebidas pode estar relacionada à doenças não herdáveis como, cáries, quadros alérgicos, formação de celulite e estrias cutâneas, alterações gastrointestinais, diabetes e câncer. O objetivo desse trabalho foi avaliar o potencial carcinogênico de diferentes concentrações de refrigerantes produzidos no município de Uberlândia, Estado de Minas Gerais, Brasil. Foi realizado o Teste de Detecção de Tumor Epitelial em Drosophila melanogaster. Larvas de terceiro estágio descendentes do cruzamento entre fêmeas virgens wts/TM3, sb¹ e machos mwh/mwh de D. melanogaster foram tratadas com diferentes concentrações (0,83; 1,66 ou 3,33 mL/g) de refrigerantes à base de cola, diet cola, laranja e limão. Os resultados mostraram aumento na frequência de tumor epitelial em moscas tratadas 3,33 mL/g de refrigerantes à base de cola e de laranja, quando comparados ao controle negativo. Os refrigerantes diet cola e limão não provocaram aumento na frequência de tumor epitelial em D. melanogaster. Em conclusão, nessas condições experimentais, os refrigerantes à base de cola e laranja mostraram potencial carcinogênico em células somáticas de D. melanogaster na concentração de 3,33 mL/g.


Assuntos
Verrugas , Bebidas Gaseificadas , Drosophila melanogaster , Testes de Mutagenicidade
9.
J Toxicol Environ Health A ; 79(12): 477-81, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27294296

RESUMO

Integration of larvivorous fish and biolarvicides at low concentrations to control of mosquito larvae in field situations may result in a safer and more effective tool. However, the usefulness of integrated approach depends upon survival and ecological fitness of fish employed. Thus, the aim of this study was to examine the genotoxic effects of combining different sublethal concentrations of spinosad, a naturally occurring neurotoxic insecticide, with male adult poecilid larvivorous guppy (Poecilia reticulata) and platy (Xiphophorus maculatus) fish on Aedes larvae mosquitos. Both fish species have been used for biological control of Aedes larvae in Brazil. Sublethal spinosad exposures were predetermined based on CL50-96hr. Nuclear abnormalities (NA) and micronucleus (MN) frequency in gill cells were measured after 14 d of exposure. Behavioral changes were monitored over 96 h. Although genotoxic effects were not markedly different from control, behavioral changes evaluated based upon the no-observable-effect concentration (NOEC) and lowest-observable-effect concentration (LOEC). Adverse effects were noted at concentrations of 12.6 mg/L (NOEC) and 25.3 mg/L (LOEC) spinosad. Therefore, these insecticide concentrations may be considered as being safe to these fish species and have important implications for integrated approach to control Aedes larvae using natural larvicides and larvivorous fish.


Assuntos
Aedes , Ciprinodontiformes/fisiologia , Inseticidas , Macrolídeos , Controle de Mosquitos , Controle Biológico de Vetores , Aedes/crescimento & desenvolvimento , Animais , Combinação de Medicamentos , Cadeia Alimentar , Larva , Poecilia
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