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1.
PLoS Genet ; 19(8): e1010721, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37639481

RESUMO

The conserved transcription factor Myc regulates cell growth, proliferation and apoptosis, and its deregulation has been associated with human pathologies. Although specific miRNAs have been identified as fundamental components of the Myc tumorigenic program, how Myc regulates miRNA biogenesis remains controversial. Here we showed that Myc functions as an important regulator of miRNA biogenesis in Drosophila by influencing both miRNA gene expression and processing. Through the analysis of ChIP-Seq datasets, we discovered that nearly 56% of Drosophila miRNA genes show dMyc binding, exhibiting either the canonical or non-canonical E-box sequences within the peak region. Consistently, reduction of dMyc levels resulted in widespread downregulation of miRNAs gene expression. dMyc also modulates miRNA processing and activity by controlling Drosha and AGO1 levels through direct transcriptional regulation. By using in vivo miRNA activity sensors we demonstrated that dMyc promotes miRNA-mediated silencing in different tissues, including the wing primordium and the fat body. We also showed that dMyc-dependent expression of miR-305 in the fat body modulates Dmp53 levels depending on nutrient availability, having a profound impact on the ability of the organism to respond to nutrient stress. Indeed, dMyc depletion in the fat body resulted in extended survival to nutrient deprivation which was reverted by expression of either miR-305 or a dominant negative version of Dmp53. Our study reveals a previously unrecognized function of dMyc as an important regulator of miRNA biogenesis and suggests that Myc-dependent expression of specific miRNAs may have important tissue-specific functions.


Assuntos
Proteínas de Drosophila , MicroRNAs , Animais , Humanos , Proteína Supressora de Tumor p53/genética , Tecido Adiposo , Drosophila/genética , MicroRNAs/genética , Nutrientes , Proteínas de Drosophila/genética , Proteínas Argonautas/genética
2.
Proc Natl Acad Sci U S A ; 120(15): e2216539120, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37014862

RESUMO

The adipose tissue plays a crucial role in metabolism and physiology, affecting animal lifespan and susceptibility to disease. In this study, we present evidence that adipose Dicer1 (Dcr-1), a conserved type III endoribonuclease involved in miRNA processing, plays a crucial role in the regulation of metabolism, stress resistance, and longevity. Our results indicate that the expression of Dcr-1 in murine 3T3L1 adipocytes is responsive to changes in nutrient levels and is subject to tight regulation in the Drosophila fat body, analogous to human adipose and hepatic tissues, under various stress and physiological conditions such as starvation, oxidative stress, and aging. The specific depletion of Dcr-1 in the Drosophila fat body leads to changes in lipid metabolism, enhanced resistance to oxidative and nutritional stress, and is associated with a significant increase in lifespan. Moreover, we provide mechanistic evidence showing that the JNK-activated transcription factor FOXO binds to conserved DNA-binding sites in the dcr-1 promoter, directly repressing its expression in response to nutrient deprivation. Our findings emphasize the importance of FOXO in controlling nutrient responses in the fat body by suppressing Dcr-1 expression. This mechanism coupling nutrient status with miRNA biogenesis represents a novel and previously unappreciated function of the JNK-FOXO axis in physiological responses at the organismal level.


Assuntos
Proteínas de Drosophila , MicroRNAs , Animais , Humanos , Camundongos , Drosophila/metabolismo , Longevidade/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Estresse Oxidativo/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Ribonuclease III/genética , Ribonuclease III/metabolismo , RNA Helicases DEAD-box/metabolismo
3.
Anticancer Agents Med Chem ; 22(15): 2788-2798, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35297353

RESUMO

BACKGROUND: The Coccoloba uvifera L. species is currently considered an important source of compounds of high biological value such as lupeol. This is related to different and important biological activities to human health. OBJECTIVE: The objective of this study was to encapsulate the C. uvifera extract in nanofibers made with the biopolymers gelatin (G)/high-grade polymerization agave fructans (HDPAF) in the proportions 1:0, 1:1, 1:2, 1:3 and 0:1, through the electrospinning process, in addition to evaluating the antimutagenic and antiproliferative properties of the encapsulated extract. METHODS: The physicochemical characteristics of the nanofibers were evaluated, as well as the antiproliferative and antimutagenic activities of the encapsulated and unencapsulated extract. SEM evaluation shows nanofibers of smooth, continuous morphology and nanometric size (50-250 nm). The TGA, FTIR-ATR, HPLC-MS analyses reveal the presence of the extract in the nanofibers. RESULTS: The extract did not show a mutagenic effect during the development of the Ames test, on the other hand, the MTT test showed the antiproliferative effect at the concentrations of 50 and 100 µg/mL of extract. CONCLUSION: The extract of C. uvifera loaded in nanofibers elaborated by electrospinning with the G/HDPAF biopolymers conserves its antimutagenic and antiproliferative properties.


Assuntos
Agave , Nanofibras , Agave/química , Biopolímeros , Frutanos/química , Frutanos/farmacologia , Gelatina , Humanos , Nanofibras/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia
4.
Anticancer Agents Med Chem ; 21(16): 2250-2257, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33397268

RESUMO

BACKGROUND: Cancer is a disease characterized by the invasion and uncontrolled growth of cells. One of the best ways to minimize the harmful effects of mutagens is through the use of natural antimutagens. In this regard, the search for new antimutagens that act in the chemoprevention could represent a promising field in this area. OBJECTIVE: In this study biological potential of 11 fractions from Coccoloba uvifera L. leaf hexane extract was evaluated by several in vitro tests. METHODS: Leaves were lyophilized and hexane extraction was performed. The extract was fractionated by column chromatography with hexane, ethyl acetate, and methanol. The antimutagenic (Ames test), antiproliferative (MTT test), and antioxidant capacity (DPPH, ABTS, and ferrous ion chelation) of the fractions were evaluated. RESULTS: Fractions 4, 6, 8, and 9 have antimutagenic activity (against sodium azide in strain TA100), fraction 11 showed antiproliferative capacity (IC50 of 24 ± 9 µg/mL in cells of HCT 116). The fractions with the highest activity were analyzed by HPLC-MS and lupeol, acacetin, and ß-sitosterol were identified. CONCLUSION: This study demonstrates, for the first time, the bioactivity of C. uvifera leaf as a new source of High Biological Value Compounds (HBVC), which can be of interest to the food and pharmaceutical industries.


Assuntos
Antimutagênicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Polygonaceae/química , Antimutagênicos/química , Antimutagênicos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Radicais Livres/antagonistas & inibidores , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Salmonella typhimurium/efeitos dos fármacos , Azida Sódica/antagonistas & inibidores , Células Tumorais Cultivadas
5.
Food Res Int ; 139: 109961, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33509511

RESUMO

The volatile compounds of five kind of cultivars of jackfruit (Artocarpus heterophyllus Lam.) grown in Nayarit, Mexico, was researched by using extraction and chromatographic methods such as headspace-solid phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS). Eighty-six volatile compounds were identified. The most prominent compounds in the analyzed cultivars were alkyl esters of 3-methylbutanoic acid. Ethyl 3-methylbutanoate was the most abundant ester in FMC, JMC and RMC cultivars (190.7-961.2 µg/kg), whereas butyl 3-methylbutanoate (152.8-205.2 µg/kg) and pentyl 3-methylbutanoate (105.1-210.9 µg/kg) were predominant in DMC and BMC cultivars. By utilizing clustering statistical techniques such as principal component analysis was possible to identify certain esters compounds (number and concentration) to differentiate each cultivar.


Assuntos
Artocarpus , Compostos Orgânicos Voláteis , Cromatografia Gasosa-Espectrometria de Massas , México , Microextração em Fase Sólida , Compostos Orgânicos Voláteis/análise
6.
Anticancer Agents Med Chem ; 21(4): 523-531, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32753023

RESUMO

BACKGROUND: Compounds with biological activities had been reported in the jackfruit. These compounds are susceptible to structural changes such as isomerization and/or loss of bonds due to environmental factors. Then, the encapsulation for protecting is a necessary process. OBJECTIVE: In this study, encapsulation of High-Value Biological Compounds (HVBC) was performed using High Degree of Polymerization Agave Fructans (HDPAF) and Whey Protein (WP) as encapsulating materials to preserve the biological properties of the HVBC. METHODS: The extract was characterized by HPLC-MS in order to show the presence of compounds with preventive or therapeutic effects on chronic degenerative diseases such as cancer. The micrographs by Scanning Electron Microscopy (SEM), Thermal Analysis (TGA and DSC), photostabilization and antiproliferation of M12.C3.F6 cell line of capsules were evaluated. RESULTS: The micrographs of the nanocapsules obtained by Scanning Electron Microscopy (SEM) showed spherical capsules with sizes between 700 and 800nm. No cracks, dents or deformations were observed. The Thermogravimetric Analysis (TGA) evidenced the decomposition of the unencapsulated extract ranging from 154 to 221°C. On the other hand, the fructan-whey protein mixture demonstrated that nanocapsules have a thermoprotective effect because the decomposition temperature of the encapsulated extract increased 32.1°C. Differential Scanning Calorimetry (DSC) exhibited similar values of the glass transition temperature (Tg) between the capsules with and without extract; which indicates that the polymeric material does not interact with the extract compounds. The photoprotection study revealed that nanocapsules materials protect the jackfruit extract compounds from the UV radiation. Finally, the cell viability on the proliferation of M12.C3.F6 cell line was not affected by powder nanocapsules without jackfruit extract, indicating that capsules are not toxic for these cells. However, microcapsules with jackfruit extract (50µg/ml) were able to inhibit significantly the proliferation cells. CONCLUSION: The encapsulation process provides thermoprotection and photostability, and the antiproliferative activity of HVBC from jackfruit extract was preserved.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Artocarpus/química , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Cápsulas/química , Cápsulas/farmacologia , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Camundongos , Tamanho da Partícula , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células Tumorais Cultivadas
7.
Nanomaterials (Basel) ; 9(12)2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31766573

RESUMO

This study focuses on the use of high degree of polymerization agave fructans (HDPAF) as a polymer matrix to encapsulate compounds of high biological value within micro- and nanostructures by electrohydrodynamic processing. In this work, ß-carotene was selected as a model compound, due to its high sensitivity to temperature, light and oxygen. Ultrafine fibers from HDPAF were obtained via this technology. These fibers showed an increase in fiber diameter when containing ß-carotene, an encapsulation efficiency (EE) of 95% and a loading efficiency (LE) of 85%. The thermogravimetric analysis (TGA) showed a 90 °C shift in the ß-carotene decomposition temperature with respect to its independent analysis, evidencing the HDPAF thermoprotective effect. Concerning the HDPAF photoprotector effect, only 21% of encapsulated ß-carotene was lost after 48 h, while non-encapsulated ß-carotene oxidized completely after 24 h. Consequently, fructans could be a feasible alternative to replace synthetic polymers in the encapsulation of compounds of high biological value.

8.
Molecules ; 24(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640255

RESUMO

The genus Erythroxylum contains species used by indigenous people of South America long before the domestication of plants. Two species, E. coca and E. novogranatense, have been utilized for thousands of years specifically for their tropane alkaloid content. While abuse of the narcotic cocaine has impacted society on many levels, these species and their wild relatives contain untapped resources for the benefit of mankind in the form of foods, pharmaceuticals, phytotherapeutic products, and other high-value plant-derived metabolites. In this review, we describe the current state of knowledge of members within the genus and the recent advances in the realm of molecular biology and biochemistry.


Assuntos
Erythroxylaceae/química , Extratos Vegetais/química , Animais , Erythroxylaceae/classificação , Humanos , Filogenia , Extratos Vegetais/farmacologia , América do Sul
9.
Foods ; 8(9)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547254

RESUMO

In this study, we characterize fructan extracts from five wild agave varieties at three ages to identify their potential use in the food industry. Physicochemical parameters (solids soluble total and pH), sugar content and fructan distribution profiles by high-performance anion-exchange chromatography (HPAEC) were evaluated. We found that the ages and variety influenced the carbohydrate content and also fructan dispersion. Two- to four-year-old plants exhibited the highest concentrations of free sugars and fructans, with a low apparent degree of polymerization (DPa) of ≤9 monomers, which highlights their potential use as prebiotics. Conversely, 10- to 12-year-old plants presented a low concentration of free sugars and fructans with a maximum DPa of 70 monomers, which can be used to obtain fractions with high, intermediate and low DPa. These fractions have a potential use in the food industry as prebiotic, soluble fibers, stabilizers and sweeteners, among others. The agave varieties Agave spp., Agave salmiana, and Agave atrovirens showed mainly fructooligosaccharides (FOSs). Due to the presence of these low molecular carbohydrates, prebiotics, fermented products and/or syrups could be obtained. A. salmiana spp. crassipina and Agave tequilana variety cenizo presented DPa ≤50 and DPa ≤70, respectively, which could be useful in the production of fructan fractions of different DPa. These fractions might be used as functional ingredients in the manufacture of a wide range of food products.

10.
PeerJ ; 7: e7300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31392090

RESUMO

The octopus fauna from the southern Caribbean is an understudied field. However, recent taxonomic work in the Colombian Caribbean has led to the discovery of several new species in the family Octopodidae. To provide molecular evidence for recent descriptions in the area (i.e., Octopus taganga, O. tayrona and Macrotritopus beatrixi) and contribute to the systematics of the family, we reconstructed the first molecular phylogenies of the family including Colombian Caribbean octopus species. Using cytochrome c oxidase subunit I and rhodopsin sequences from specimens collected in three sites (Santa Marta, Old Providence and San Andrés Islands) we inferred maximum-likelihood trees and delimited species with PTP. Our mitochondrial analysis supported the monophyly of species found in the area (i.e., O. taganga, O. hummelincki and O. briareus). The genetic distinction of the species O. tayrona and O. insularis was not resolved, as these were found in one clade together with Caribbean O. vulgaris and O. aff. tayrona species (O. spB) and delimited as a single species. Additionally, our results suggest a distant relationship of the Type I O. vulgaris group (Caribbean region) from the other forms of the species complex (Old World and Brazil). Lastly, the third newly described species M. beatrixi emerged as an independent lineage and was delimited as a single species. However, its relationship to other species of its genus remains unknown due to the lack of sequences in databases. Altogether, our molecular approach to the octopus fauna from the southern Caribbean adds on information to the relationship of Octopodidae species world-wide by providing sequences from recently described species from an understudied region. Further studies employing higher taxon sampling and more molecular information are needed to fill taxonomic gaps in the area and account for single-locus resolution on the systematics of this group.

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