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1.
Proc Natl Acad Sci U S A ; 120(22): e2221483120, 2023 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-37216508

RESUMEN

The enzymatic decarboxylation of fatty acids (FAs) represents an advance toward the development of biological routes to produce drop-in hydrocarbons. The current mechanism for the P450-catalyzed decarboxylation has been largely established from the bacterial cytochrome P450 OleTJE. Herein, we describe OleTPRN, a poly-unsaturated alkene-producing decarboxylase that outrivals the functional properties of the model enzyme and exploits a distinct molecular mechanism for substrate binding and chemoselectivity. In addition to the high conversion rates into alkenes from a broad range of saturated FAs without dependence on high salt concentrations, OleTPRN can also efficiently produce alkenes from unsaturated (oleic and linoleic) acids, the most abundant FAs found in nature. OleTPRN performs carbon-carbon cleavage by a catalytic itinerary that involves hydrogen-atom transfer by the heme-ferryl intermediate Compound I and features a hydrophobic cradle at the distal region of the substrate-binding pocket, not found in OleTJE, which is proposed to play a role in the productive binding of long-chain FAs and favors the rapid release of products from the metabolism of short-chain FAs. Moreover, it is shown that the dimeric configuration of OleTPRN is involved in the stabilization of the A-A' helical motif, a second-coordination sphere of the substrate, which contributes to the proper accommodation of the aliphatic tail in the distal and medial active-site pocket. These findings provide an alternative molecular mechanism for alkene production by P450 peroxygenases, creating new opportunities for biological production of renewable hydrocarbons.


Asunto(s)
Alquenos , Ácidos Grasos , Ácidos Grasos/metabolismo , Alquenos/química , Descarboxilación , Sistema Enzimático del Citocromo P-450/metabolismo , Oxidación-Reducción
2.
Mol Cell ; 67(1): 5-18.e19, 2017 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-28673542

RESUMEN

Processive elongation of RNA Polymerase II from a proximal promoter paused state is a rate-limiting event in human gene control. A small number of regulatory factors influence transcription elongation on a global scale. Prior research using small-molecule BET bromodomain inhibitors, such as JQ1, linked BRD4 to context-specific elongation at a limited number of genes associated with massive enhancer regions. Here, the mechanistic characterization of an optimized chemical degrader of BET bromodomain proteins, dBET6, led to the unexpected identification of BET proteins as master regulators of global transcription elongation. In contrast to the selective effect of bromodomain inhibition on transcription, BET degradation prompts a collapse of global elongation that phenocopies CDK9 inhibition. Notably, BRD4 loss does not directly affect CDK9 localization. These studies, performed in translational models of T cell leukemia, establish a mechanism-based rationale for the development of BET bromodomain degradation as cancer therapy.


Asunto(s)
Quinasa 9 Dependiente de la Ciclina/metabolismo , Proteínas Nucleares/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Elongación de la Transcripción Genética , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Animales , Antineoplásicos/farmacología , Proteínas de Ciclo Celular , Quinasa 9 Dependiente de la Ciclina/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Regulación Leucémica de la Expresión Génica , Células HCT116 , Células HEK293 , Humanos , Células Jurkat , Ratones Endogámicos NOD , Ratones SCID , Ratones Transgénicos , Complejos Multiproteicos , Proteínas Nucleares/genética , Péptido Hidrolasas/genética , Péptido Hidrolasas/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Estabilidad Proteica , Proteolisis , ARN Polimerasa II/metabolismo , Factores de Tiempo , Elongación de la Transcripción Genética/efectos de los fármacos , Factores de Transcripción/genética , Transfección , Ubiquitina-Proteína Ligasas , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Microb Cell Fact ; 23(1): 145, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778337

RESUMEN

Recombinant multiepitope proteins (RMPs) are a promising alternative for application in diagnostic tests and, given their wide application in the most diverse diseases, this review article aims to survey the use of these antigens for diagnosis, as well as discuss the main points surrounding these antigens. RMPs usually consisting of linear, immunodominant, and phylogenetically conserved epitopes, has been applied in the experimental diagnosis of various human and animal diseases, such as leishmaniasis, brucellosis, cysticercosis, Chagas disease, hepatitis, leptospirosis, leprosy, filariasis, schistosomiasis, dengue, and COVID-19. The synthetic genes for these epitopes are joined to code a single RMP, either with spacers or fused, with different biochemical properties. The epitopes' high density within the RMPs contributes to a high degree of sensitivity and specificity. The RMPs can also sidestep the need for multiple peptide synthesis or multiple recombinant proteins, reducing costs and enhancing the standardization conditions for immunoassays. Methods such as bioinformatics and circular dichroism have been widely applied in the development of new RMPs, helping to guide their construction and better understand their structure. Several RMPs have been expressed, mainly using the Escherichia coli expression system, highlighting the importance of these cells in the biotechnological field. In fact, technological advances in this area, offering a wide range of different strains to be used, make these cells the most widely used expression platform. RMPs have been experimentally used to diagnose a broad range of illnesses in the laboratory, suggesting they could also be useful for accurate diagnoses commercially. On this point, the RMP method offers a tempting substitute for the production of promising antigens used to assemble commercial diagnostic kits.


Asunto(s)
Epítopos , Escherichia coli , Proteínas Recombinantes , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/inmunología , Humanos , Epítopos/inmunología , Epítopos/genética , Pruebas Inmunológicas/métodos , Animales , COVID-19/diagnóstico
4.
Br J Nutr ; 131(9): 1591-1599, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38174420

RESUMEN

This study evaluated changes in the use of sweeteners over one decade and the relationship between socio-demographics, diet and weight status with the type of sweetener. Data came from the Brazilian National Dietary Surveys of 2008-2009 and 2017-2018, including ≥ 10-year-old individuals (n 32 749; n 44 744, respectively, after excluding pregnant and lactating women). The use of table sugar, non-caloric sweeteners (NCS), both or none was reported through a specific question. Food consumption was assessed using two non-consecutive food records (2008-2009) and 24-h recalls (2017-2018). For the last survey, means of energy, macro and micronutrient intake, food groups' contribution (%) to daily energy intake and age- and energy-adjusted nutrient intake were estimated according to the type of sweetener used. Differences in means and proportions across the categories of sweeteners used were evaluated based on the 95 % CI. All analyses were stratified by sex and considered sample design and weights. Over 10 years, the use of table sugar decreased by 8 %, while the habit of not using any sweetener increased almost three times, and the use of NCS remained stable. Larger reductions in the use of table sugar were observed in the highest income level and among men. Regardless of sex, compared with NCS users, table sugar users had greater mean intake of energy, carbohydrates and added sugar and lower micronutrient intake means. Although table sugar is still the most used sweetener, the increased choice of 'no sweetener' is noteworthy in Brazil.


Asunto(s)
Azúcares de la Dieta , Ingestión de Energía , Humanos , Brasil , Femenino , Masculino , Adulto , Adulto Joven , Niño , Adolescente , Azúcares de la Dieta/análisis , Azúcares de la Dieta/administración & dosificación , Persona de Mediana Edad , Dieta , Edulcorantes no Nutritivos/administración & dosificación , Edulcorantes , Encuestas sobre Dietas , Factores Socioeconómicos
5.
Nutr Metab Cardiovasc Dis ; 34(4): 1069-1079, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38220511

RESUMEN

BACKGROUND AND AIMS: Recently, new indices combining routine and low-cost anthropometric and biochemical measurements have emerged. Among them, the visceral adiposity index (VAI) and lipid accumulation product (LAP) are being investigated for the prediction of altered blood pressure (BP) and insulin resistance (IR). Therefore, this study aimed to evaluate whether visceral adiposity index (VAI) and height-corrected lipid accumulation product (HLAP) are predictors of cardiometabolic risk in Brazilian adolescents. METHODS AND RESULTS: Data were obtained from the Cardiovascular Risk in Adolescents (ERICA) study, a cross-sectional, national, multicenter, school-based survey conducted between 2013 and 2014 in Brazil. The sample consisted of 37,815 adolescents aged 12-17 years of both genders attending the last 3 years of elementary or secondary school from public and private schools located in 273 municipalities with more than 100,000 inhabitants. A Poisson regression was performed to verify associations between VAI and HLAP indices and the presence of altered BP and IR according to sex. In addition, receiver operating characteristic curve (ROC) analysis was applied to compare the predictive ability and determine the cut-off points of the VAI and HLAP indices in identifying cardiometabolic risk obtained by altered BP and IR. The prevalences of altered BP and IR were 24.49 % (95 % confidence interval [CI]: 23.14-25.87) and 24.22 % (95 % CI: 22.70-25.80), respectively. CONCLUSIONS: The VAI and HLAP indices are good predictors of cardiometabolic risk in Brazilian adolescents. HLAP showed better performance in identifying insulin resistance in males.


Asunto(s)
Enfermedades Cardiovasculares , Resistencia a la Insulina , Adolescente , Femenino , Humanos , Masculino , Adiposidad , Antropometría , Índice de Masa Corporal , Brasil/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Estudios Transversales , Obesidad Abdominal/diagnóstico , Obesidad Abdominal/epidemiología , Niño
6.
Mol Ther ; 31(2): 409-419, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36369741

RESUMEN

The accumulation of soluble oligomers of the amyloid-ß peptide (AßOs) in the brain has been implicated in synapse failure and memory impairment in Alzheimer's disease. Here, we initially show that treatment with NUsc1, a single-chain variable-fragment antibody (scFv) that selectively targets a subpopulation of AßOs and shows minimal reactivity to Aß monomers and fibrils, prevents the inhibition of long-term potentiation in hippocampal slices and memory impairment induced by AßOs in mice. As a therapeutic approach for intracerebral antibody delivery, we developed an adeno-associated virus vector to drive neuronal expression of NUsc1 (AAV-NUsc1) within the brain. Transduction by AAV-NUsc1 induced NUsc1 expression and secretion in adult human brain slices and inhibited AßO binding to neurons and AßO-induced loss of dendritic spines in primary rat hippocampal cultures. Treatment of mice with AAV-NUsc1 prevented memory impairment induced by AßOs and, remarkably, reversed memory deficits in aged APPswe/PS1ΔE9 Alzheimer's disease model mice. These results support the feasibility of immunotherapy using viral vector-mediated gene delivery of NUsc1 or other AßO-specific single-chain antibodies as a potential therapeutic approach in Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer , Anticuerpos de Cadena Única , Ratones , Ratas , Humanos , Animales , Anciano , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/metabolismo , Anticuerpos de Cadena Única/genética , Anticuerpos de Cadena Única/metabolismo , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Sinapsis/metabolismo , Neuronas/metabolismo , Trastornos de la Memoria/genética , Trastornos de la Memoria/terapia
7.
Chem Biodivers ; 21(3): e202301508, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38092696

RESUMEN

Dillenia indica (Linn.) has been reported by several biological activities, including anti-inflammatory, antioxidant, antidiabetic, anti-hyperglycemic, antiproliferative, antimutagenic, anticholinesterase, and antimicrobial. In Brazilian traditional medicine, the fruits of D. indica have been used to treat general topical pain and inflammation, but with no scientific validation. Thus, aiming to study its chemical constitution and antinociceptive properties, the crude extract (CE) and fractions obtained from the fruits of D. indica were submitted to an in vivo pharmacological evaluation and a dereplication study by LC-MS/MS analysis, assisted by the Global Natural Product Social Molecular Networking (GNPS). The oral antinociceptive activity of the fruits of D. indica and the possible participation of the opioid and cannabinoid systems were demonstrated in the formalin-induced nociception model. The chemical dereplication study led us to identify several known chemical constituents, including flavonoids, such as caffeoylmalic acid, naringenin, quercetin, and kaempferol. According to literature data, our results are compatible with significant antinociceptive and anti-inflammatory activities. Therefore, the flavonoid constituents of the fruits of D. indica are probably responsible for its antioxidant, anti-inflammatory, and antinociceptive effects mediated by both opioid and cannabinoid systems, confirming its folk use in the treatment and relief of pain.


Asunto(s)
Analgésicos , Dilleniaceae , Analgésicos/química , Analgésicos Opioides/efectos adversos , Extractos Vegetales/química , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Cromatografía Liquida , Espectrometría de Masas en Tándem , Antiinflamatorios/farmacología , Dolor/tratamiento farmacológico , Flavonoides/uso terapéutico
8.
Artículo en Inglés | MEDLINE | ID: mdl-38869621

RESUMEN

Biosilica (BS) and spongin (SPG) from marine sponges are highlighted for their potential to promote bone regeneration. Moreover, 3D printing is introduced as a technology for producing bone grafts with optimized porous structures, allowing for better cell attachment, proliferation, and differentiation. Thus, this study aimed to characterize the BS and BS/SPG 3D printed scaffolds and to evaluate the biological effects in vitro. The scaffolds were printed using an ink containing 4 wt.% of sodium alginate. The physicochemical characteristics of BS and BS/SPG 3D printed scaffolds were analyzed by SEM, EDS, FTIR, porosity, evaluation of mass loss, and pH measurement. For in vitro analysis, the cellular viability of the MC3T3-E1 cell lineage was assessed using the AlamarBlue® assay and confocal microscopy, while genotoxicity and mineralization potential were evaluated through the micronucleus assay and Alizarin Red S, respectively. SEM analysis revealed spicules in BS, the fibrillar structure of SPG, and material degradation over the immersion period. FTIR indicated peaks corresponding to silicon oxide in BS samples and carbon oxide and amine in SPG samples. BS-SPG scaffolds exhibited higher porosity, while BS scaffolds displayed greater mass loss. pH measurements indicated a significant decrease induced by BS, which was mitigated by SPG over the experimental periods. In vitro studies demonstrated the biocompatibility and non-cytotoxicity of scaffold extracts. .Also, the scaffolds promoted cellular differentiation. The micronucleus test further confirmed the absence of genotoxicity. These findings suggest that 3D printed BS and BS/SPG scaffolds may possess desirable morphological and physicochemical properties, indicating in vitro biocompatibility.

9.
BMC Oral Health ; 24(1): 383, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528527

RESUMEN

BACKGROUND: The evidence in the literature suggests that some skeletal or dental malocclusions are involved with dental development, resulting in advanced or delayed dental age (DA). The purpose of this systematic review was to investigate the association between DA and different types of malocclusions. METHODS: The search was carried out on PubMed, Scopus, Web of Science, Virtual Health Library, and in the gray literature. Observational studies that evaluated the association between DA and sagittal, vertical, or transversal malocclusions were included. The quality assessment was performed using the Newcastle-Ottawa Scale (NOS). The data from primary studies were narratively synthesized. The certainty of evidence was evaluated using the GRADE approach. The study was conducted from August 2023 to October 2023. RESULTS: One Thousand Nine Hundred Ninety-One records were identified in the initial search. Twenty (n = 20) studies were included. Most of the studies (n=15) presented a moderate quality according to NOS. Twelve studies evaluated the association between DA and sagittal discrepancies; eight studies evaluated vertical discrepancies, and only one study analyzed a transversal discrepancy. Demirjian's method for DA assessment was the most used among the studies. The primary studies observed that patients of both sexes presenting a vertical growth pattern and males with skeletal Class III malocclusion tend to have advanced DA. The study that investigated transversal malocclusion found that unilateral posterior cross-bite is associated with delayed DA. The certainty of evidence was very low for all outcomes evaluated. CONCLUSION: DA may be associated with the type of malocclusion. It is suggested that DA can be used as an initial diagnostic tool in orthodontics. Future well-designed studies should be performed in order to investigate the association between DA and different types of malocclusions in more detail. TRIAL REGISTRATION: This study was registered in the PROSPERO database (CRD42023454207).


Asunto(s)
Maloclusión de Angle Clase III , Maloclusión , Diente , Masculino , Femenino , Humanos , Maloclusión/complicaciones
10.
Physiol Plant ; 175(4): e13984, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37616001

RESUMEN

Elevated [CO2 ] (E[CO2 ]) mitigates agricultural losses of C4 plants under drought. Although several studies have described the molecular responses of the C4 plant species Sorghum bicolor during drought exposure, few have reported the combined effects of drought and E[CO2 ] (E[CO2 ]/D) on the roots. A previous study showed that, among plant organs, green prop roots (GPRs) under E[CO2 ]/D presented the second highest increase in biomass after leaves compared with ambient [CO2 ]/D. GPRs are photosynthetically active and sensitive to drought. To understand which mechanisms are involved in the increase in biomass of GPRs, we performed transcriptome analyses of GPRs under E[CO2 ]/D. Whole-transcriptome analysis revealed several pathways altered under E[CO2 ]/D, among which photosynthesis was strongly affected. We also used previous metabolome data to support our transcriptome data. Activities associated with photosynthesis and central metabolism increased, as seen by the upregulation of photosynthesis-related genes, a rise in glucose and polyol contents, and increased contents of chlorophyll a and carotenoids. Protein-protein interaction networks revealed that proliferation, biogenesis, and homeostasis categories were enriched and contained mainly upregulated genes. The findings suggest that the previously reported increase in GPR biomass of plants grown under E[CO2 ]/D is mainly attributed to glucose and polyol accumulation, as well as photosynthesis activity and carbon provided by respiratory CO2 refixation. Our findings reveal that an intriguing and complex metabolic process occurs in GPRs under E[CO2 ]/D, showing the crucial role of these organs in plant drought /tolerance.


Asunto(s)
Sorghum , Sorghum/genética , Sorghum/metabolismo , Biomasa , Dióxido de Carbono/metabolismo , Azúcares , Sequías , Clorofila A , Fotosíntesis/fisiología , Hojas de la Planta/metabolismo , Glucosa
11.
Nature ; 543(7644): 270-274, 2017 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-28241139

RESUMEN

Recurrent chromosomal translocations producing a chimaeric MLL oncogene give rise to a highly aggressive acute leukaemia associated with poor clinical outcome. The preferential involvement of chromatin-associated factors as MLL fusion partners belies a dependency on transcription control. Despite recent progress made in targeting chromatin regulators in cancer, available therapies for this well-characterized disease remain inadequate, prompting the need to identify new targets for therapeutic intervention. Here, using unbiased CRISPR-Cas9 technology to perform a genome-scale loss-of-function screen in an MLL-AF4-positive acute leukaemia cell line, we identify ENL as an unrecognized gene that is specifically required for proliferation in vitro and in vivo. To explain the mechanistic role of ENL in leukaemia pathogenesis and dynamic transcription control, a chemical genetic strategy was developed to achieve targeted protein degradation. Acute loss of ENL suppressed the initiation and elongation of RNA polymerase II at active genes genome-wide, with pronounced effects at genes featuring a disproportionate ENL load. Notably, an intact YEATS chromatin-reader domain was essential for ENL-dependent leukaemic growth. Overall, these findings identify a dependency factor in acute leukaemia and suggest a mechanistic rationale for disrupting the YEATS domain in disease.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Leucemia/genética , Leucemia/metabolismo , Dominios Proteicos , Transcripción Genética , Factores de Elongación Transcripcional/química , Factores de Elongación Transcripcional/metabolismo , Animales , Sistemas CRISPR-Cas , Línea Celular Tumoral , Proliferación Celular , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Epigénesis Genética , Edición Génica , Genoma/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Humanos , Leucemia/patología , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Ratones , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Proteolisis , ARN Polimerasa II/metabolismo , Elongación de la Transcripción Genética , Factores de Transcripción/química , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Factores de Elongación Transcripcional/genética
12.
Nature ; 543(7644): 265-269, 2017 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-28241141

RESUMEN

Cancer cells are characterized by aberrant epigenetic landscapes and often exploit chromatin machinery to activate oncogenic gene expression programs. Recognition of modified histones by 'reader' proteins constitutes a key mechanism underlying these processes; therefore, targeting such pathways holds clinical promise, as exemplified by the development of bromodomain and extra-terminal (BET) inhibitors. We recently identified the YEATS domain as an acetyl-lysine-binding module, but its functional importance in human cancer remains unknown. Here we show that the YEATS domain-containing protein ENL, but not its paralogue AF9, is required for disease maintenance in acute myeloid leukaemia. CRISPR-Cas9-mediated depletion of ENL led to anti-leukaemic effects, including increased terminal myeloid differentiation and suppression of leukaemia growth in vitro and in vivo. Biochemical and crystal structural studies and chromatin-immunoprecipitation followed by sequencing analyses revealed that ENL binds to acetylated histone H3, and co-localizes with H3K27ac and H3K9ac on the promoters of actively transcribed genes that are essential for leukaemia. Disrupting the interaction between the YEATS domain and histone acetylation via structure-based mutagenesis reduced the recruitment of RNA polymerase II to ENL-target genes, leading to the suppression of oncogenic gene expression programs. Notably, disrupting the functionality of ENL further sensitized leukaemia cells to BET inhibitors. Together, our data identify ENL as a histone acetylation reader that regulates oncogenic transcriptional programs in acute myeloid leukaemia, and suggest that displacement of ENL from chromatin may be a promising epigenetic therapy, alone or in combination with BET inhibitors, for aggressive leukaemia.


Asunto(s)
Acetilación , Regulación Neoplásica de la Expresión Génica , Histonas/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Oncogenes/genética , Factores de Elongación Transcripcional/metabolismo , Animales , Sistemas CRISPR-Cas , Línea Celular Tumoral , Epigénesis Genética , Femenino , Edición Génica , Histonas/química , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Lisina/metabolismo , Ratones , Regiones Promotoras Genéticas/genética , Unión Proteica/efectos de los fármacos , Dominios Proteicos , ARN Polimerasa II/metabolismo , Transcripción Genética , Factores de Elongación Transcripcional/química , Factores de Elongación Transcripcional/deficiencia , Factores de Elongación Transcripcional/genética
13.
Nutr Metab Cardiovasc Dis ; 33(4): 685-697, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36870914

RESUMEN

AIMS: To perform a systematic review to investigate the association between adolescents' a posteriori dietary patterns with diabetes-related biomarkers (fasting blood glucose, fasting insulinemia, glycated hemoglobin and homeostatic model assessment insulin resistance index (HOMA-IR)). DATA SYNTHESIS: Review registered with PROSPERO under number CRD42020185369. Studies with adolescents aged 10-19 years that identified dietary patterns by a posteriori methods were included. The databases used included: PubMed, SCOPUS, Web of Science, Food Science and Technology Abstracts, CINAHL, SPORTDiscus, Lilacs/BVS, The Cochrane Central Register of Controlled Trials, ProQuest Dissertations&Theses Global and Capes Theses Bank and Brazilian Digital Library of Theses and Dissertations. Risk of bias was assessed via the Agency for Healthcare Research and Quality tool. Eight cross-sectional studies that evaluated 6438 adolescents (55.5% females) were included. For fasting blood glucose, the results were inconsistent and some studies found no association for the dietary patterns called traditional (57%), Western (42%) and healthy (28%). For the fasting insulinemia and HOMA-IR outcomes, the Western dietary pattern showed a positive association or higher means in 60% and 50% of the studies, respectively. No studies that evaluated glycated hemoglobin were found. CONCLUSION: Fasting insulinemia and HOMA-IR outcomes were positively associated with the Western dietary patterns. The studies reviewed did not present consistent evidence of an association with western, healthy and traditional dietary patterns with fasting blood glucose, as the results were conflicting or did not show statistical significance.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Femenino , Humanos , Adolescente , Masculino , Hemoglobina Glucada , Glucemia , Estudios Transversales , Ayuno , Insulina , Biomarcadores
14.
Parasitol Res ; 123(1): 64, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38117414

RESUMEN

This study aimed to investigate the effect of rosuvastatin treatment on anxiety-related behavior and short- and long-term memory impairment in mice infected with acute RH and BRI strains of Toxoplasma gondii. Balb/C mice were infected intraperitoneally and after 2 h, oral treatment with rosuvastatin (40 mg/kg/day) was initiated for 4 days. Behaviors related to anxiety and locomotion were evaluated in the open field (OF), and short- and long-term memory through the novel object recognition test (NOR). At the end of the experiments, peritoneal fluid, brain, liver, and lung were collected for T. gondii DNA quantification and histopathological analysis. Infection with BRI strain reduced the dwell time and central locomotion in the OF (p < 0.05), indicating anxiogenic type behavior, while treatment with rosuvastatin reversed this response (p < 0.05). RH strain infection did not alter any behavior in the OF (p > 0.05) and both strains impaired short- and long-term memory (NOR test), but with no significant treatment effect (p > 0.05). The BRI strain was shown to be more damaging in relation to anxiogenic type behavior when compared to the RH strain (p < 0.05), whereas rosuvastatin reduced this damaging effect in BRI. The treatment reduced the parasite load in the peritoneal lavage, liver, and lung of animals infected with both acute strains; however, it significantly (p < 0.05) attenuated the inflammatory process only in BRI-infected and treated animals, showing that non-archetypal genotypes are more damaging in rodents. This suggests that rosuvastatin may be a drug with great therapeutic potential against T. gondii mainly to reduce damage from virulent strains.


Asunto(s)
Toxoplasma , Animales , Ratones , Rosuvastatina Cálcica/uso terapéutico , Brasil , Inflamación/tratamiento farmacológico , Ratones Endogámicos BALB C
15.
Bioprocess Biosyst Eng ; 46(7): 1053-1063, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37199771

RESUMEN

Collagen dressings have been widely used as effective treatments for chronic wounds acting as barrier, protecting the area from infections and participating in the healing process. Collagen from fish skin is biocompatible, presents low immunogenicity and is able of stimulating wound healing. In this scenario, skin of flounder fish (Paralichthys sp.) may constitute a promising source for collagen. Then, our hypothesis is that fish collagen is able of increasing cell proliferation, with no cytotoxicity. In this context, the aim of the present study was to investigate the physicochemical and morphological properties of collagen using scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDS), mass loss and pH. Moreover, the cytotoxicity and genotoxicity of collagen were studied using in vitro studies (cell viability, comet assay and micronucleus assay). Fish collagen showed no variation of pH and mass weight, with characteristic peaks of collagen in FTIR. Furthermore, all the extracts presented cell viability at least over 50% and no cytotoxicity was observed. Regarding genotoxicity data, the results showed that only the extract of 100% showed higher values in comparison with negative control group for CHO-K1 cell line as depicted by comet and micronucleus assays. Based on the results, it is suggested that fish collagen is biocompatible and present non-cytotoxicity in the in vitro studies, being considered a suitable material for tissue engineering proposals.


Asunto(s)
Lenguado , Cricetinae , Animales , Colágeno/farmacología , Cicatrización de Heridas , Piel/química , Peces , Células CHO
16.
J Environ Sci Health B ; 58(3): 203-209, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36775896

RESUMEN

Euphorbia hirta L. is a weed species that is tolerant to the most used herbicide in agriculture, glyphosate. The anatomical characteristics of plants influence the processes of absorption and translocation of herbicides. The objective of this work was to characterize the anatomy of the aerial vegetative axis (leaves and stem) of E. hirta, to support the establishment of strategies for better control of this species with herbicides. The plants were grown in a greenhouse under controlled conditions. When they reached sizes between 8 and 12 cm, samples of stems and leaves were collected, fixed in FAA 50, and stored in 70% ethanol. Subsequently, the samples were processed following usual light microscopy techniques. In cross-section, the stem of E. hirta has a circular shape. The leaf epidermis is uniseriate composed of isodiametric cells of compact arrangement and with the presence of multicellular trichomes and anthocyanin. As for the morphometric parameters evaluated, the young leaves have a lower thickness in the abaxial epidermis. Based on the anatomical characteristics observed in E. hirta, the main barriers that can act in the absorption of herbicides are the high hairiness and the high content of anthocyanin in the epidermal cells.


Asunto(s)
Euphorbia , Herbicidas , Antocianinas , Herbicidas/farmacología , Hojas de la Planta , Glifosato
17.
Cell Tissue Res ; 388(3): 489-502, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35451648

RESUMEN

Collagen extracted from fishes has been appearing as an alternative for commercial porcine and bovine collagen and it has been considered interesting especially for membrane manufacturing in tissue engineering. Despite the positive in vitro effects of fish collagen membranes, there is still no understanding of all the benefits that this natural biomaterial plays in the wound healing process, due to the lack of compilation of the results obtained in animal studies. In this sense, the purpose of this study was to perform a systematic review of the literature to examine the effects of fish collagen membranes for skin wound healing in experimental models of skin wound. The search was carried out according to the orientations of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and the descriptors of the Medical Subject Headings (MeSH) were defined: "fish," collagen," "skin," and "in vivo". A total of 10 articles were retrieved from the databases PubMed and Scopus. After the elegibility analyses, this review covers the different origins of fish collagen reported in the different papers from the beginning of 2015 through the middle of 2021. The results were based mainly on histological analysis and macroscopic evaluation, and fish skin collagen was responsible for improving the wound healing rate and the process of reepithelization and collagen deposition. In conclusion, fish skin collagen has shown positive results in in vivo studies and may be a potential biomaterial in tissue engineering.


Asunto(s)
Colágeno , Cicatrización de Heridas , Animales , Materiales Biocompatibles/farmacología , Bovinos , Colágeno/farmacología , Peces , Piel , Porcinos
18.
Br J Nutr ; 127(9): 1404-1414, 2022 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-34176526

RESUMEN

Se reduces cellular inflammation and lipid peroxides; therefore, its association with CVD and the metabolic syndrome (MetS) has been studied. We aimed to investigate the association between Se intake and the MetS and its parameters (high waist circumference, hyperglycaemia, high blood pressure, high TAG and low HDL-cholesterol) in Brazilian adolescents between 12 and 17 years old. This research is part of the Study of Cardiovascular Risks in Adolescents (ERICA), a Brazilian nationwide school-based study with regional and national relevance. We assessed: (1) socio-demographic data (sex, age, type of school and maternal education) using a self-administered questionnaire; (2) dietary intake using a 24-h recall applied for the whole sample and a second one applied to a subsample to allow within-person variability adjustment; (3) anthropometric data (weight, height, waist circumference) and blood pressure using standardised procedures; and (4) biochemical analyses (fasting glucose, TAG and HDL-cholesterol). Logistic regression was applied, basing the analysis on a theoretical model. Median Se intake was 98·3 µg/d. Hypertension and hyperglycaemia were more prevalent among boys, while a high waist circumference was more frequent in girls, and low HDL-cholesterol levels were higher among private school students. The prevalence of the MetS was 2·6 %. No association between the MetS and its parameters and Se intake was found. This lack of association could be due to an adequate Se intake in the studied population.


Asunto(s)
Enfermedades Cardiovasculares , Hiperglucemia , Hipertensión , Síndrome Metabólico , Selenio , Masculino , Femenino , Humanos , Adolescente , Niño , Síndrome Metabólico/epidemiología , Factores de Riesgo , Enfermedades Cardiovasculares/epidemiología , Brasil/epidemiología , Glucemia/análisis , Factores de Riesgo de Enfermedad Cardiaca , Circunferencia de la Cintura , Colesterol , Índice de Masa Corporal , Triglicéridos
19.
Nutr Metab Cardiovasc Dis ; 32(12): 2689-2704, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36336548

RESUMEN

AIMS: To conduct a systematic review of the literature on the scientific evidence of the oral intake of omega-3 and omega-6 FAs and metabolic syndrome (MS) in adolescents. DATA SYNTHESIS: The study was registered in PROSPERO (number 42020185370). Studies were carried out with adolescents aged 10-19 years, who presented as intervention/exposure the oral intake of omega-3 and/or omega-6 fatty acids (FAs), in the databases PubMed, Scopus, Web of Science, LILACS, CENTRAL, and PQDT Global e BDTD. The tools used to assess the risk of bias were RoB 2.0, Agency for Healthcare Research and Quality (AHRQ), and Newcastle-Ottawa Scale. Fifteen papers retrieved published from 2010 to 2019 were included (n = 3534); nine were randomized studies and controlled clinical trials, four were cross-sectional studies, one was a retrospective cohort study, and one case-control study. No studies have evaluated the effect or association of omega-3 and/or of omega-6 FAs with actual MS, only with its components. The randomized clinical trials identified the effects of omega-3 FA on the decrease in blood pressure (n = 1 out of six), glycemia (n = 2 out of seven), and triglycerides (n = 5 out of eight), and the increase in HDL-c (n = 2 out of eight) considering the comparison between the group that received omega-3 FA and the control group. CONCLUSIONS: Scientific evidence is controversial on the association between oral intake of omega-3 FAs and MS in adolescents, due to the heterogeneity between studies and the divergence of results for the same MS component.


Asunto(s)
Ácidos Grasos Omega-3 , Síndrome Metabólico , Humanos , Estados Unidos , Adolescente , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Síndrome Metabólico/prevención & control , Estudios de Casos y Controles , Estudios Retrospectivos , Ácidos Grasos Omega-6/efectos adversos , Ácidos Grasos Omega-3/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto
20.
Nutr Metab Cardiovasc Dis ; 32(11): 2603-2611, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36163217

RESUMEN

BACKGROUND AND AIM: We assessed the Ideal Cardiovascular Health (CVH) in Brazilian adolescents according to demographics and socioeconomic characteristics. METHODS AND RESULTS: This is a cross-sectional study with data from the Study of Cardiovascular Risks in Adolescents (ERICA), with a nationwide representative sample of 36,956 Brazilian adolescents, aged 12-17 years, enrolled in public and private schools. The CVH metrics considered were body mass index (BMI), physical activity, smoking, healthy diet score, blood pressure, fasting plasma glucose, and total cholesterol. The demographics and socioeconomic characteristics analyzed were sex, age, race/skin color, and type of school attended. The study design was considered, and the significant difference determined by the non-overlapping of 95% Confidence Interval. The mean ideal CVH score was 4.0, higher for females, adolescents aged 15-17 years, and students from private schools. The prevalence of ideal fasting plasma glucose was 96%, of non-smoking 95.6%, of ideal blood pressure 75.5%, of ideal BMI 73.2%, of ideal total cholesterol 55.4%, of ideal physical activity 45.2%, and only 0.5% had an ideal diet. The prevalence of ideal CVH metrics varied according to demographics and socioeconomic characteristics. CONCLUSION: Females, older adolescents, and students who attended private school had a better CVH. Demographics and socioeconomic characteristics were associated with CVH metrics. The low ideal proportions found for diet and physical activity are of concern and reinforce the need for food and nutritional educational actions designed to promote healthy behaviors in adolescence to prevent the development of cardiovascular diseases.


Asunto(s)
Enfermedades Cardiovasculares , Adolescente , Glucemia , Presión Sanguínea , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Colesterol , Estudios Transversales , Femenino , Estado de Salud , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Factores de Riesgo
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