Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 684
Filtrar
1.
Animals (Basel) ; 14(9)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38731273

RESUMEN

This study aimed to assess the impact of palm oil deodorizer distillate (POD) on the ruminal environment, including (i) microbial community, (ii) ruminal degradability, and (iii) apparent digestibility in sheep. The data used were derived from twenty rumen-cannulated sheep fed five isoproteic and isofiber diets based on elephant grass (Pennisetum purpureum Schum. cv. Roxo) silage supplemented with 0, 25, 50, 75, or 100 g kg-1 POD on a dry matter (DM) basis. Rumen fluid samples were collected three hours after feeding directly from the ventral sac of the rumen via a cannula and then subjected to DNA extraction, which was subsequently used for 16S rDNA amplification, followed by sequencing and diversity analysis. In this study, the microbial diversity was dominated by Bacteroidetes and Firmicutes, followed by Euryarchaetoa, Actinobacteria, and Tenericutes, in the ruminal environment, and was slightly modified when supplemented with the POD up to 100 g/kg (10%), leading to only a slight decrease in the diversity index. The ruminal degradability, ruminal fermentation parameters, and apparent digestibility were slightly compromised by the inclusion of up to 25 g of POD per kg of DM, and larger inclusions interfered with the ruminal degradability of fibrous fractions and the apparent digestibility of dry matter. This lipid supplement showed good results for feeding sheep and is an inexpensive and abundant alternative in the regional market.

2.
J Toxicol Environ Health A ; 87(12): 497-515, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38619158

RESUMEN

One prominent aspect of Parkinson's disease (PD) is the presence of elevated levels of free radicals, including reactive oxygen species (ROS). Syagrus coronata (S. coronata), a palm tree, exhibits antioxidant activity attributed to its phytochemical composition, containing fatty acids, polyphenols, and flavonoids. The aim of this investigation was to examine the potential neuroprotective effects of S. coronata fixed oil against rotenone-induced toxicity using Drosophila melanogaster. Young Drosophila specimens (3-4 d old) were exposed to a diet supplemented with rotenone (50 µM) for 7 d with and without the inclusion of S. coronata fixed oil (0.2 mg/g diet). Data demonstrated that rotenone exposure resulted in significant locomotor impairment and increased mortality rates in flies. Further, rotenone administration reduced total thiol levels but elevated lipid peroxidation, iron (Fe) levels, and nitric oxide (NO) levels while decreasing the reduced capacity of mitochondria. Concomitant administration of S. coronata exhibited a protective effect against rotenone, as evidenced by a return to control levels of Fe, NO, and total thiols, lowered lipid peroxidation levels, reversed locomotor impairment, and enhanced % cell viability. Molecular docking of the oil lipidic components with antioxidant enzymes showed strong binding affinity to superoxide dismutase (SOD) and glutathione peroxidase (GPX1) enzymes. Overall, treatment with S. coronata fixed oil was found to prevent rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.


Asunto(s)
Trastornos del Movimiento , Rotenona , Animales , Drosophila melanogaster , Simulación del Acoplamiento Molecular , Estrés Oxidativo , Antioxidantes/farmacología , Óxido Nítrico/metabolismo
3.
ACS Omega ; 9(12): 13556-13591, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38559945

RESUMEN

Alzheimer's disease (AD) is the most common form of neurodegenerative dementia that is rapidly becoming a major health problem, especially in developed countries because of their increasing life expectancy. Two main problems are often associated with the disease: (i) the absence of a widely accessible "gold-standard" for early diagnosis and (ii) lack of effective therapies with disease-modifying effects. The recent success of the monoclonal antibody lecanemab played an important role not only in clarifying a possible druggable pathway but also in spelling the revival of small molecule drug discovery. Unlike bulky biologics, small molecules are structurally less complex, generally cheaper, and compatible with at-home oral consumption, making it feasible for people to start their drug regimen early and stay on it longer. In this sense, small-molecule near-infrared fluorescent theranostics have been gaining more and more attention from the scientific community, as they have the potential to simultaneously provide diagnostic outputs and deliver therapeutic action, paving the way toward personalized medicine in AD patients. They also have the potential to shift the diagnostic "status-quo" from expensive and limited-access PET radiotracers toward inexpensive and handy imaging tools widely available for primary patient screening and preclinical animal studies. Herein, we review the most recent advances in the field of fluorescent theranostics for Alzheimer's disease, detailing their design strategies, synthetic approaches and imaging and therapeutic properties in vitro and in vivo. With this Review, we intend to provide a milestone in the acquired knowledge in the field of AD theranostics, encouraging the future development of properly designed theranostic compounds with improved chances to reach clinical applications.

4.
J Hazard Mater ; 471: 134243, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38657506

RESUMEN

Iron-magnetic nanoparticles (Fe-NMPs) are widely used in environmental remediation, while porphyrin-based hybrid materials anchored to silica-coated Fe3O4-nanoparticles (Fe3O4-NPs) have been used for water disinfection purposes. To assess their safety on plants, especially concerning potential environmental release, it was investigated for the first time, the impact on plants of a silica-coated Fe3O4-NPs bearing a porphyrinic formulation (FORM) - FORM@NMP. Additionally, FORM alone and the magnetic nanoparticles without FORM anchored (NH2@NMP) were used for comparison. Wheat (Triticum aestivum L.) was chosen as a model species and was subjected to three environmentally relevant doses during germination and tiller development through root application. Morphological, physiological, and metabolic parameters were assessed. Despite a modest biomass decrease and alterations in membrane properties, no major impairments in germination or seedling development were observed. During tiller phase, both Fe3O4-NPs increased leaf length, and photosynthesis exhibited varied impacts: both Fe3O4-NPs and FORM alone increased pigments; only Fe3O4-NPs promoted gas exchange; all treatments improved the photochemical phase. Regarding oxidative stress, lipid peroxidation decreased in FORM and FORM@NMP, yet with increased O2-• in FORM@NMP; total flavonoids decreased in NH2@NMP and antioxidant enzymes declined across all materials. Phenolic profiling revealed a generalized trend towards a decrease in flavones. In conclusion, these nanoparticles can modulate wheat physiology/metabolism without apparently inducing phytotoxicity at low doses and during short-time exposure. ENVIRONMENTAL IMPLICATION: Iron-magnetic nanoparticles are widely used in environmental remediation and fertilization, besides of new applications continuously being developed, making them emerging contaminants. Soil is a major sink for these nanoparticles and their fate and potential environmental risks in ecosystems must be addressed to achieve more sustainable environmental applications. Furthermore, as the reuse of treated wastewater for agricultural irrigation is being claimed, it is of major importance to disclose the impact on crops of the nanoparticles used for wastewater decontamination, such as those proposed in this work.


Asunto(s)
Germinación , Porfirinas , Triticum , Triticum/crecimiento & desarrollo , Triticum/efectos de los fármacos , Triticum/metabolismo , Germinación/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Nanopartículas de Magnetita/toxicidad , Nanopartículas de Magnetita/química , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Dióxido de Silicio/toxicidad , Dióxido de Silicio/química , Estrés Oxidativo/efectos de los fármacos
5.
J Bras Nefrol ; 46(3): e20230193, 2024.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-38591823

RESUMEN

Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.


Asunto(s)
Nefrología , Patología Clínica , Insuficiencia Renal Crónica , Humanos , Tasa de Filtración Glomerular , Creatinina , Brasil , Consenso , Diálisis Renal , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia
6.
Toxicol In Vitro ; 98: 105824, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38614139

RESUMEN

The TRPV1 receptor, which is known to contribute significantly to pain perception, has recently been identified as a useful tool for predicting eye stinging potential in cosmetics. In this study, HEK-293 cells with high TRPV1 expression were utilized to evaluate calcium influx related to receptor activation triggered by chemicals and cosmetic formulations. The cells were exposed to increasing concentrations of substances to cause or not some aggression to the eye, and TRPV1 activity was assessed by measuring intracellular FURA-2 AM fluorescence signal. To confirm TRPV1 channel activation, capsazepine, a capsaicin antagonist, was employed in addition to using capsaicin as a positive control. The study's results indicate that this novel model can identify compounds known to cause some aggression to the eye, such as stinging, considering a cut-off value of 60% of Ca2+ influx exposed to the lowest evaluated concentration (0.00032%). When applied to the cosmetic baby formulation, although the presented model exhibited higher sensitivity by classifying as stinging formulations that had previously undergone clinical testing and were deemed non-stinging, the assay could serve as a valuable in vitro tool for predicting human eye stinging sensation and can be used as a tier 1 in an integrated testing strategy.

7.
Pharmaceuticals (Basel) ; 17(3)2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38543071

RESUMEN

Since the beginning of the XXI century, Leishmaniasis has been integrated into the World Health Organization's list of the 20 neglected tropical diseases, being considered a public health issue in more than 88 countries, especially in the tropics, subtropics, and the Mediterranean area. Statistically, this disease presents a world prevalence of 12 million cases worldwide, with this number being expected to increase shortly due to the 350 million people considered at risk and the 2-2.5 million new cases appearing every year. The lack of an appropriate and effective treatment against this disease has intensified the interest of many research groups to pursue the discovery and development of novel treatments in close collaboration with the WHO, which hopes to eradicate it shortly. This paper intends to highlight the quinoline scaffold's potential for developing novel antileishmanial agents and provide a set of structural guidelines to help the research groups in the medicinal chemistry field perform more direct drug discovery and development programs. Thus, this review paper presents a thorough compilation of the most recent advances in the development of new quinoline-based antileishmanial agents, with a particular focus on structure-activity relationship studies that should be considerably useful for the future of the field.

8.
Microorganisms ; 12(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38543558

RESUMEN

Palm oil derived from the fruits of Elaeis guineensis Jacq. has global economic importance and is largely produced in tropical regions. The palm oil production process leads to a highly polluting waste called palm oil mill effluent (POME). A strategy commonly used by producers to overcome environmental issues and to improve soil fertility is the reuse of POME as a fertilizer due to the chemical and biological characteristics of the effluent. In this research, three groups were analyzed: soil without POME application (control group) and soil samples after 4 and 9 days of POME application. An environmental DNA metabarcoding approach was used. eDNA was extracted, and the V4 region of the 16S rRNA gene was amplified and sequenced in the Illumina MiSeq platform. The abundance of Proteobacteria (48.1%) and Firmicutes (9.0%) was higher in fertilized soil, while Bacteroidetes (20.3%) and Verrucomicrobia (7.8%) were more abundant in control soil. Additionally, the effluent seemed to modify soil characteristics favoring taxa responsible for the mineralization of organic compounds and nitrogen fixation such as species of Gammaproteobacteria class. Our study highlights the influence of POME on soil biological components and contributes to the sustainable production of palm oil in the Amazon.

9.
Pharmaceutics ; 16(2)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38399315

RESUMEN

Type 2 diabetes mellitus (DM) continues to escalate, necessitating innovative therapeutic approaches that target distinct pathways and address DM complications. Flavonoids have been shown to possess several pharmacological activities that are important for DM. This study aimed to evaluate the in vivo effects of the flavonoid melanoxetin using Goto-Kakizaki rats. Over a period of 14 days, melanoxetin was administered subcutaneously to investigate its antioxidant, anti-inflammatory, and antidiabetic properties. The results show that melanoxetin reduced insulin resistance in adipose tissue by targeting protein tyrosine phosphatase 1B. Additionally, melanoxetin counteracted oxidative stress by reducing nitrotyrosine levels and modulating superoxide dismutase 1 and hemeoxygenase in adipose tissue and decreasing methylglyoxal-derived hydroimidazolone (MG-H1), a key advanced glycation end product (AGE) implicated in DM-related complications. Moreover, the glyoxalase 1 expression decreased in both the liver and the heart, correlating with reduced AGE levels, particularly MG-H1 in the heart. Melanoxetin also demonstrated anti-inflammatory effects by reducing serum prostaglandin E2 levels, and increasing the antioxidant status of the aorta wall through enhanced acetylcholine-dependent relaxation in the presence of ascorbic acid. These findings provide valuable insights into melanoxetin's therapeutic potential in targeting multiple pathways involved in type 2 DM, particularly in mitigating oxidative stress and glycation.

10.
Front Psychiatry ; 15: 1279072, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38356910

RESUMEN

Background: Transcranial Magnetic Stimulation (TMS) is used for in vivo assessment of human motor cortical excitability, with application of TMS pulses over the motor cortex resulting in muscle responses that can be recorded with electromyography (EMG) as Motor Evoked Potentials (MEPs). These have been widely explored as potential biomarkers for neuropsychiatric disorders but methodological heterogeneity in acquisition, and inherent high variability, have led to constraints in reproducibility. Normalization, consisting in scaling the signal of interest to a known and repeatable measurement, reduces variability and is standard practice for between-subject comparisons of EMG. The effect of normalization on variability of MEP amplitude has not yet been explored and was assessed here using several methods. Methods: Three maximal voluntary isometric contractions (MVICs) and 40 MEPs were collected from the right hand in healthy volunteers, with a retest session conducted 4 to 8 weeks later. MEP amplitude was normalized using either external references (MVICs) or internal references (extreme MEPs). Iterative re-sampling of 30 normalized MEPs per subject was repeated 5,000 times to define, for each normalization method, distributions for between-subject coefficients of variation (CV) of the mean MEP amplitude. Intra-class correlation coefficients (ICC) were used to assess the impact of normalization on test­retest stability of MEP amplitude measurements. Results: In the absence of normalization, MEPs collected from the right hand of 47 healthy volunteers were within reported values regarding between-subject variability (95% confidence intervals for the CV: [1.0567,1.0577]) and showed good temporal stability (ICC = 0.77). Internal reference normalization substantially reduced between-subject variability, by values of up to 64%, while external reference normalization had no impact or increased between-subject variability. Normalization with the smallest references reduced test­retest stability, with use of the largest references resulting in slight reduction or improvement of ICCs. Internal reference normalization using the largest MEPs was found to be robust to several sensitivity analyses. Conclusion: Internal, but not external, reference normalization reduces between-subject variability of MEP amplitude, and has a minimal impact on within-subject variability when conducted with the largest references. Additional research is necessary to further validate these normalization methods toward potential use of MEPs as biomarkers of neuropsychiatric disorders.

11.
PeerJ ; 12: e16513, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38313017

RESUMEN

Background: Corynebacterium pseudotuberculosis is a zoonotic Gram-positive bacterial pathogen known to cause different diseases in many mammals, including lymph node abscesses in camels. Strains from biovars equi and ovis of C. pseudotuberculosis can infect camels. Comparative genomics could help to identify features related to host adaptation, and currently strain Cp162 from biovar equi is the only one from camel with a sequenced genome. Methods: In this work, we compared the quality of three genome assemblies of strain Cp162 that used data from the DNA sequencing platforms SOLiD v3 Plus, IonTorrent PGM, and Illumina HiSeq 2500 with an optical map and investigate the unique features of this strain. For this purpose, we applied comparative genomic analysis on the different Cp162 genome assembly versions and included other 129 genomes from the same species. Results: Since the first version of the genome, there was an increase of 88 Kbp and 121 protein-coding sequences, a decrease of pseudogenes from 139 to 53, and two inversions and one rearrangement corrected. We identified 30 virulence genes, none associated to the camel host, and the genes rpob2 and rbpA predicted to confer resistance to rifampin. In comparison to 129 genomes of the same species, strain Cp162 has four genes exclusively present, two of them code transposases and two truncated proteins, and the three exclusively absent genes lysG, NUDIX domain protein, and Hypothetical protein. All 130 genomes had the rifampin resistance genes rpob2 and rbpA. Our results found no unique gene that could be associated with tropism to camel host, and further studies should include more genomes and genome-wide association studies testing for genes and SNPs.


Asunto(s)
Corynebacterium pseudotuberculosis , Animales , Ovinos/genética , Corynebacterium pseudotuberculosis/genética , Camelus/genética , Genoma Bacteriano/genética , Estudio de Asociación del Genoma Completo , Rifampin , Análisis de Secuencia de ADN
12.
Foods ; 13(4)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38397517

RESUMEN

Brown macroalgae are rich sources of nutrients and health-promoting compounds. Nevertheless, their consumption is still limited by their strong organoleptic characteristics, thus requiring the development of extraction strategies to profit from their nutritional value. To fulfil this, two sequential extraction approaches were developed, differing in the solvent used in the first extraction step, water in approach 1 or food-grade ethanol in approach 2, to obtain economic and affordable extracts rich in specific compounds from Fucus vesiculosus. The use of water in the first step of extraction allowed us to recover water-soluble phlorotannins, laminarans and mannuronic-rich alginates, making the subsequent 70% ethanol extract richest in fucoxanthin (0.07% algae DW), and the hot water fractions purest in fucoidans and alginates with a lower mannuronic-to-guluronic (M/G) ratio (2.91). Conversely, when beginning extraction procedures with 96% ethanol, the recovered yields of phlorotannins increased (0.43 g PGE/100 g algae DW), but there was a concomitant seven-fold decrease in the recovery of fucoxanthin in the subsequent 70% ethanol extract. This approach also led to less pure hot water fractions containing fucoidans, laminarans and alginates with a higher M/G ratio (5.50). Overall, this work unveiled the potential of the first extraction steps in sustainable and holistic cascade strategies to modulate the composition of food-grade extracts, creating prospects of their application as tailored functional ingredients in food products.

13.
iScience ; 27(3): 109100, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38405606

RESUMEN

Influenza A virus (IAV) employs multiple strategies to manipulate cellular mechanisms and support proper virion formation and propagation. In this study, we performed a detailed analysis of the interplay between IAV and the host cells' proteostasis throughout the entire infectious cycle. We reveal that IAV infection activates the inositol requiring enzyme 1 (IRE1) branch of the unfolded protein response, and that this activation is important for an efficient infection. We further observed the accumulation of virus-induced insoluble protein aggregates, containing both viral and host proteins, associated with a dysregulation of the host cell RNA metabolism. Our data indicate that this accumulation is important for IAV propagation and favors the final steps of the infection cycle, more specifically the virion assembly. These findings reveal additional mechanisms by which IAV disrupts host proteostasis and uncovers new cellular targets that can be explored for the development of host-directed antiviral strategies.

14.
Toxicology ; 503: 153750, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38360295

RESUMEN

Occupational asthma covers a group of work-related diseases whose clinical manifestations include airway hyperresponsiveness and airflow limitation. Although the chemical respiratory allergy (CRA) induced by Low Molecular Weight (LMW) sensitizers is a major concern, especially in terms of the regulatory framework, to date there are no methods available for preclinically addressing this toxicological outcome, as its mechanistic background is not fully understood at molecular or cellular levels. This paper proposes a mechanistic study applying New Approach Methodologies (NAM) of the pro-inflammatory and functional effects triggered by LMW respiratory allergens in different respiratory tract cell lines, including bronchial epithelial (BEAS-2B), lung fibroblast (MRC-5), and endothelial cells (EA.hy926), and an analysis of the capacity of such chemicals to interact with the mucin protein, to address certain toxicodynamic aspects of such compounds. The results showed that some of the sensitizers evaluated interact with mucin, the main protein mucus component, but the toxicant-mucin complex formation does not seem to be a common feature of different chemical classes of allergens. At a cellular level, sensitizers promoted an increase in IL-8, IL-6, and IL-1ß production in the evaluated cell types. It also impaired the MUC1 expression by bronchial cells and activated endothelial cells, thereby increasing the ICAM-I surface expression. Taken together, our results showed that these aforementioned cell types participate in the CRA Adverse Outcome Pathway and must be considered when developing preclinical testing strategies, particularly investigating danger signal production after exposure to LMW sensitizers in different tissue compartments.


Asunto(s)
Células Endoteliales , Pulmón , Humanos , Bronquios/metabolismo , Biomarcadores/metabolismo , Alérgenos/toxicidad , Mucinas
15.
Toxicology ; 503: 153756, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38369009

RESUMEN

Chemical Respiratory Allergy (CRA) is triggered after exposure to Low Molecular Weight (LMW) sensitizers and manifests clinically as asthma and rhinitis. From a risk/toxicity assessment point of view, there are few methods, none of them validated, for evaluating the respiratory sensitization potential of chemicals once the in vivo-based models usually employed for inhalation toxicity addressment do not comprise allergenicity endpoints specifically. Based on that, we developed, characterized, and evaluated the applicability of a 3D-tetraculture airway model reconstructed with bronchial epithelial, fibroblasts, endothelial and monocytic cell lines. Moreover, we exposed the tissue to maleic anhydride (MA) aerosols to challenge the model and subsequently assessed inflammatory and functional aspects of the tissue. The reconstructed tissue presented phenotypic biomarkers compatible with human bronchial epithelium, and MA aerosol exposure triggered an increased IL-8 and IL-6 production, reactive oxygen species (ROS) formation, and apoptosis of epithelial cells. Besides, augmented IL-8 production by monocytic cells was also found, correlating with dendritic cell activation within the co-culture model after MA exposure. Our results demonstrated that the 3D-tetraculture bronchial model presents hallmarks related to human airways' structure and function. Additionally, exposure to a respiratory sensitizer induced inflammatory and functional alterations in the reconstructed tissue, rendering it a valuable tool for exploring the mechanistic framework of chemically induced respiratory sensitization.


Asunto(s)
Asma , Interleucina-8 , Humanos , Interleucina-8/metabolismo , Aerosoles y Gotitas Respiratorias , Bronquios , Asma/metabolismo , Células Epiteliales/metabolismo
16.
Toxicol Res (Camb) ; 13(1): tfae005, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38239269

RESUMEN

Background: Pesticides are indispensable for the cultivation of crops, especially those of economic importance, such as soybeans. Data on the annual use of herbicides in crops show that they correspond to 50%, making it the most used in agriculture. Aim: Therefore, the aim of this study was to evaluate the toxicity of the three commercial herbicides (clomazone, glyphosate, and sulfentrazone) in THP-1 cells. Methods: Cells were incubated with 0-5,000 mg/L of the herbicides for 24 h at 37 °C for cytotoxicity evaluation. Additionally, a few toxicological pathways such as reactive species generation, mitochondrial impairment, and interleukin profile, which have been previously involved in the toxicity of pesticides, were also evaluated. Results: A potential immunotoxic effect of the herbicides on THP-1 cells was observed, especially glyphosate, as it is a powerful agent of cellular immunotoxicity. It was also possible to verify an increase in oxidative stress and IL-8 levels and mitochondrial dysfunction. Conclusion: All herbicides showed cytotoxic effects in THP-1 monocytes, which were related to mitochondrial impairment.

17.
Nature ; 626(7999): 583-592, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38092040

RESUMEN

Animals exhibit a diverse behavioural repertoire when exploring new environments and can learn which actions or action sequences produce positive outcomes. Dopamine release after encountering a reward is critical for reinforcing reward-producing actions1-3. However, it has been challenging to understand how credit is assigned to the exact action that produced the dopamine release during continuous behaviour. Here we investigated this problem in mice using a self-stimulation paradigm in which specific spontaneous movements triggered optogenetic stimulation of dopaminergic neurons. Dopamine self-stimulation rapidly and dynamically changes the structure of the entire behavioural repertoire. Initial stimulations reinforced not only the stimulation-producing target action, but also actions similar to the target action and actions that occurred a few seconds before stimulation. Repeated pairings led to a gradual refinement of the behavioural repertoire to home in on the target action. Reinforcement of action sequences revealed further temporal dependencies of refinement. Action pairs spontaneously separated by long time intervals promoted a stepwise credit assignment, with early refinement of actions most proximal to stimulation and subsequent refinement of more distal actions. Thus, a retrospective reinforcement mechanism promotes not only reinforcement, but also gradual refinement of the entire behavioural repertoire to assign credit to specific actions and action sequences that lead to dopamine release.


Asunto(s)
Dopamina , Aprendizaje , Refuerzo en Psicología , Recompensa , Animales , Ratones , Toma de Decisiones/fisiología , Dopamina/metabolismo , Neuronas Dopaminérgicas/metabolismo , Aprendizaje/fisiología , Optogenética , Factores de Tiempo , Modelos Psicológicos , Modelos Neurológicos
18.
Chem Biodivers ; 21(2): e202301536, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38090811

RESUMEN

Bauhinia ungulata is an antioxidant medicinal plant that has been manipuled in Brazil to lower glycemic index as well is for alternative treatment for diabetes. Therefore, the present hearch has aimed to investigates the antioxidant effects of the essential oil of Bauhinia ungulata L. (EOBU) collected in Amazon region better specified in Boa Vista, Roraima, Brazil, located in the Amazon region. Gas chromatography had been used to characterize the components, and antioxidant assays such as DPPH, TAC, reducing power, Fe2+ chelation, and total phenols had also been performed. The major constituents had molecularly anchored with the human catalase (CAT) enzyme, and maltol has showed as a positive control. Among the 25 revealed components, the main ones have been α-bisabolol (27.2 %), ß-Caryophyllene (12.5 %) and Epi-γ-eudesmol (13.6 %). The EOBU has comproved a TAC value of 618.79 mg of ascorbic acid equivalent, free radical scavenging capacity (DPPH) around 53.7 % and 65.27 %, Fe2+ chelation capacity of 161±6 and 126.7±39.6, for 0.1 mg.mL-1 and 0.5 mg.mL-1 , respectively. The power around the EOBU has appeared percentages equals to 28.66 %, 44.6 %, and 77.03 % in the concentrations tested. As well as, 96.5 % of total phenols. The compounds α-bisabolol (-5.7±0.4 Kcal.mol-1 ) and ß-caryophyllene (-6.1±0.5 Kcal.mol-1 ) have showed good interaction with CAT compared to Maltol (-4.4±0.4 Kcal.mol-1 ). The present work has demonstrated that EOBU functions as a potent antioxidant, capable of scavenging free radicals and reducing oxidative stress damage.


Asunto(s)
Bauhinia , Sesquiterpenos Monocíclicos , Aceites Volátiles , Sesquiterpenos Policíclicos , Humanos , Antioxidantes/farmacología , Antioxidantes/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Fenoles/química , Extractos Vegetales/química
19.
Altern Lab Anim ; 52(1): 60-68, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38061994

RESUMEN

The Brazilian National Network of Alternative Methods (RENAMA), which is linked to the Ministry of Science, Technology and Innovation, is currently comprised of 51 laboratories from CROs, academia, industry and government. RENAMA's aim is to develop and validate new approach methodologies (NAMs), as well as train researchers and disseminate information on their use - thus reducing Brazilian, and consequently Latin American, dependence on external technology. Moreover, it promotes the adoption of NAMs by educators and trained researchers, as well as the implementation of good laboratory practice (GLP) and the use of certified products. The RENAMA network started its activities in 2012, and was originally comprised of three central laboratories - the National Institute of Metrology, Quality and Technology (INMETRO); the National Institute of Quality Control in Health (INCQS); and the National Brazilian Biosciences Laboratory (LNBio) - and ten associated laboratories. In 2022, RENAMA celebrated its 10th anniversary, a milestone commemorated by the organisation of a meeting attended by different stakeholders, including the RENAMA-associated laboratories, academia, non-governmental organisations and industry. Ninety-six participants attended the meeting, held on 26 May 2022 in Balneário Camboriú, SC, Brazil, as part of the programme of the XXIII Brazilian Congress of Toxicology 2022. Significant moments of the RENAMA were remembered, and new goals and discussion themes were established. The lectures highlighted recent innovations in the toxicological sciences that have translated into the assessment of consumer product safety through the use of human-relevant NAMs instead of the use of existing animal-based approaches. The challenges and opportunities in accepting such practices for regulatory purposes were also presented and discussed.


Asunto(s)
Aniversarios y Eventos Especiales , Laboratorios , Animales , Humanos , Brasil
20.
Codas ; 35(6): e20210189, 2023.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-38055408

RESUMEN

PURPOSE: To analyze the association between hearing loss and health vulnerability in children aged 25 to 36 months. METHODS: Analytical observational cross-sectional study conducted through child hearing screening in nine day-care centers. The screening consisted of anamnesis, otoscopy, tympanometry, transient otoacoustic emissions, and pure tone audiometry. For each exam performed, the 'pass' and 'fail' criteria were established. The children's residential addresses were georeferenced and a choropleth map of the spatial distribution was built, considering the Health Vulnerability Index (HVI). The analysis of the association between the HVI and the variables sex, auditory assessment, and region area of the household was performed using Pearson's Chi-square and Fisher's Exact tests. RESULTS: Ninety-five children of both sexes were evaluated, of which 44.7% presented alterations in at least one of the exams performed, being referred for otorhinolaryngological evaluation and subsequent auditory assessment. Of the observed changes, 36.9% occurred in the tympanometry and 7.8% in the transient otoacoustic emissions. Among children referred for reassessment, 9.7% were diagnosed with conductive hearing loss, 13.6% results within normal limits and 21.4% did not attend for assessment. Of the children who presented the final diagnosis of conductive hearing loss (9.7%), 1.9% were classified as low-risk HVI and 6.8% as medium-risk HVI. There was statistical significance between HVI and the child's place of residence. CONCLUSION: The association between hearing loss and HIV was not statistically significant; however, it was possible to observe that 77.7% of the children with hearing loss resided in sectors with medium- risk HIV.


OBJETIVO: Analisar a associação entre perda auditiva e a vulnerabilidade à saúde em crianças na faixa etária de 25 a 36 meses. MÉTODO: Estudo observacional analítico do tipo transversal realizado por meio da triagem auditiva infantil em nove creches. A triagem constou de anamnese, meatoscopia, timpanometria, emissões otoacústicas transientes e audiometria tonal limiar. Para cada exame realizado foi estabelecido o critério de "passa" e "falha". Os endereços residenciais das crianças foram georreferenciados e foi construído mapa coroplético da distribuição espacial, considerando o Índice de Vulnerabilidade à Saúde (IVS). Foi realizada análise de associação entre o IVS com as variáveis sexo, exames audiológicos e regional de domicílio por meio dos testes Qui-quadrado de Pearson, e Exato de Fisher. RESULTADOS: Foram avaliadas 95 crianças de ambos os sexos, destas, 44,7% apresentaram alteração em pelo menos um dos exames realizados, sendo encaminhadas para avaliação otorrinolaringológica e auditiva. Das alterações observadas 36,9% ocorreram na timpanometria e 7,8% nas emissões otoacústicas transientes. Dentre crianças encaminhadas para avaliação, 9,7% apresentaram diagnóstico de perda auditiva do tipo condutiva, 13,6% resultados dentro da normalidade e 21,4% não compareceram para reavaliação. Das crianças que apresentaram o diagnóstico final de perda auditiva do tipo condutiva (9,7%), 1,9% foi classificado como IVS de risco baixo e 6,8% como IVS de risco médio. Houve significância estatística entre IVS e o local de residência da criança. CONCLUSÃO: Não houve associação com significância estatística entre alteração auditiva e IVS, entretanto foi possível observar que 77,7% das crianças com diagnóstico de perda auditiva residiam em setores censitários de risco médio do IVS.


Asunto(s)
Sordera , Pérdida Auditiva , Masculino , Niño , Femenino , Humanos , Pérdida Auditiva Conductiva/diagnóstico , Prevalencia , Estudios Transversales , Emisiones Otoacústicas Espontáneas , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/epidemiología , Pruebas de Impedancia Acústica , Audiometría de Tonos Puros
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...