Glutathione S-transferases (GSTs) are a key enzyme superfamily involved in the detoxification and cytoprotection of a wide variety of xenobiotics, such as carcinogens, anticancer drugs, environmental ...toxicants, and endogenously produced free radicals. In the liver, the hGSTA1 isoenzyme is the most abundant and catalyzes the glutathione conjugation of a wide range of electrophiles and has been the principal GST responsible for xenobiotic detoxification. Given the critical role of this enzyme in several cellular processes, particularly cell detoxification, understanding the molecular mechanisms underlying the regulation of hGSTA1 expression is critical. Therefore, the aim of the present study was to investigate whether AHR is involved in the modulation of hGSTA1 gene expression and to characterize the molecular mechanism through which AHR exerts this regulation. Two xenobiotic response elements (XREs) were located at −602 bp and −1030 bp from the transcription start site at the hGSTA1 gene promoter. After treatment of HepG2 cells with beta-naphthoflavone (β-NF), an AHR agonist, induction of hGSTA1 mRNA was observed. This effect was mediated by the recruitment of AHR to the hGSTA1 gene promoter and its transactivation, as indicated by the ChIP, EMSA and luciferase activity assays. The increase in hGSTA1 transcription regulated by AHR also resulted in enhanced levels of hGSTA1 protein and activity. Taken together, our data suggest that AHR ligands have the potential to modify xenobiotic and endobiotic metabolism mediated by hGSTA1, thereby altering the detoxification of xenobiotics, steroidogenesis and the efficacy of chemotherapeutic agents.
•β-NF treatment resulted in increased hGSTA1 activity in HepG2 cells.•β–NF–mediated induction of hGSTA1 expression is at transcriptional level.•β–NF–mediated induction of hGSTA1 is AHR-dependent.•AHR activation promotes its recruitment to the hGSTA1 gene promoter.
Obesity is the main challenge for public health systems. Functional foods have emerged as an alternative to the ineffectiveness of pharmacological therapies. However, it is necessary to investigate ...to find sources of raw material for its preparation. The aim of this work was to evaluate the functional effects of residual avocado seed in diet-induced obese mice. Animals were fed a high-fat diet supplemented with avocado seed (1.25%) for 6 weeks. Body weight, food intake, satiety, physical activity, and energy expenditure-involved gene expression were measured. Supplementation with avocado seed led to reduced body weight, delayed satiety, increased physical activity, and induced Dio2 and Adrb1 expression in hypothalamus and white adipose tissue, respectively. No changes in markers of hepatic injury were observed. In conclusion, avocado seed exerts functional effects on obese mice, by promoting energy expenditure, without toxicity effects, making it possible to use this by-product in the development of functional foods.
Massive left atrium thrombus Santos, Paula Martínez; López, Elena Batlle; Barrio, Elena España ...
The International Journal of Cardiovascular Imaging,
2014/1, Letnik:
30, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The image shows a left atrium completely occupied by a giant non-homogeneous, irregularly-surfaced mass, obstructing the disc motion, mimicking severe mitral prosthetic stenosis.
The aim of the present work was to evaluate MTX treatment (0.1, 1 and 10 μg mL−1) in vitro in order to characterize its effects on cell proliferation alterations in cell cycle of HaCaT keratinocytes ...and wound healing in a Skh1 mice treated with MTX (low doses 30 mg kg−1, high doses 200 mg kg−1 and repeated doses at 1.5 mg kg−1). We analyzed the cytotoxic effect of methotrexate by a resazurin assay. The effects in the proliferation, cell cycle and apoptosis of HaCaT cells were analyzed by flow cytometry. The effects of MTX on wound healing in vivo were also analyzed. A trend toward reduction in the resazurin assay was found (p > 0.05). Reduced proliferation was also identified in a clonogenic assay and a CFSE assay (p < 0.05) due to the MTX treatment. A reduction in the G2/M and S phases was observed accompanied by apoptosis induction with increased sub G0 phase and annexin V FITC staining. Effect of MTX was evidenced in vivo on the wound closure process after day 10 (p < 0.05) with alterations in tissue architecture and remodeling. There is a marked effect of MTX on wound healing in vivo in Skh1 mice with implications for long-term therapy and surgical interventions.
•Methotrexate (MTX) treatment has anti-proliferative effects on keratinocytes in a in vitro.•High concentrations of MTX cause arrest of cell cycle in G0/G1 phase.•MTX induces apoptosis in HACAT cells.•Repeated doses of MTX cause a delay during the proliferation phase of wound healing in vivo.•MTX impair wound healing in vivo altering the architecture of tissue and reducing basal and corneal stratum thickness.
SUMMARY
Background
Mexican children are characterized by a high‐starch intake diet and high prevalence of obesity.
Objectives
To investigate the association of AMY1A/AMY2A copy numbers (CNs) and ...AMY1/AMY2 serum enzymatic activity with childhood obesity in up to 427 and 337 Mexican cases and controls.
Methods
Anthropometric and dietary starch intake data were collected. CN of AMY1A/AMY2A and AMY1/AMY2 serum enzymatic activity were determined using droplet digital PCR (ddPCR) and enzymatic colorimetry, respectively. An individual participant level data meta‐analysis of association between AMY1A CNVs and obesity was also performed.
Results
A positive association between AMY1A/AMY2A CNs and their corresponding AMY1/AMY2 serum enzyme activity was observed in children with normal weight and obesity. The serum enzyme activity of AMY1 and AMY2 was negatively associated with childhood obesity risk, and the association was restricted to kids eating medium/high amount of starch (Pinteraction = .004). While no association between AMY1A and AMY2A CNs and childhood obesity was observed in our sample, we confirmed a significant association between AMY1A CN and obesity in a meta‐analysis of 3100 Mexican children.
Conclusions
Our data suggest that genetically determined salivary and pancreatic amylase activity can increase/decrease the risk of obesity in Mexican children, this effect being blunted by a low‐starch diet.
Equivalence – Equivalence responding (Barnes et al., 1997), based on derived or non-explicitly trained relational responding, supports a behaviour-analytic model of analogical reasoning. Conditional ...discriminations are the most common procedure used to train its prerequisites. In this exploratory work we test Vaughan’s (1988) simple discrimination procedure instead to derive Eq-Eq responses in children. Two factors were assessed: type of reinforcer used (primary or secondary) and age of participants (9-10 or 12-13 years). The procedure successfully leaded to the derivation of equivalence – equivalence responses, and both factors influenced the results: selecting older children and applying primary reinforcement leaded to faster learning and better results in the equivalence – equivalence test. No interaction between factors was found. This training procedure can provide a new way to investigate the behavioural prerequisites of this important ability
Equivalence – Equivalence responding (Barnes et al., 1997), based on derived or non-explicitly trained relational responding, supports a behaviour-analytic model of analogical reasoning. Conditional ...discriminations are the most common procedure used to train its prerequisites. In this exploratory work we test Vaughan’s (1988) simple discrimination procedure instead to derive Eq-Eq responses in children. Two factors were assessed: type of reinforcer used (primary or secondary) and age of participants (9-10 or 12-13 years). The procedure successfully leaded to the derivation of equivalence – equivalence responses, and both factors influenced the results: selecting older children and applying primary reinforcement leaded to faster learning and better results in the equivalence – equivalence test. No interaction between factors was found. This training procedure can provide a new way to investigate the behavioural prerequisites of this important ability
La respuesta de equivalencia – equivalencia (Barnes, Hegarty y Smeets, 1997), basada en la derivación sin entrenamiento explícito de respuestas relacionales, ha servido para fundamentar un modelo analítico – funcional de razonamiento analógico. Tradicionalmente, el procedimiento utilizado para la derivación de estas respuestas se ha basado en discriminaciones condicionales. En este trabajo se explora la utilización del procedimiento de partición para la formación de clases de equivalencia funcional de Vaughan (1988) como base para la derivación de estas relaciones más complejas en niños, investigando el papel del tipo de reforzador utilizado (primario o secundario) y la edad de los participantes (9-10 años o 12-13 años). Los resultados del experimento indican que el procedimiento de partición da lugar a la derivación de relaciones de equivalencia – equivalencia, con influencia de ambos factores: Los niños de mayor edad, y aquellos a los que se aplica reforzamiento primario aprenden la tarea en menos ensayos y derivan en mayor proporción la respuesta relacional.
No se encontró interacción entre los factores. El procedimiento de partición puede aportar una nueva vía de investigación para esclarecer os prerrequisitos conductuales de esta importante habilidad.
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