Recent reports indicate that (−)-epicatechin can exert cardioprotective actions, which may involve endothelial nitric oxide synthase (eNOS)-mediated nitric oxide production in endothelial cells. ...However, the mechanism by which (−)-epicatechin activates eNOS remains unclear. In this study, we proposed to identify the intracellular pathways involved in (−)-epicatechin-induced effects on eNOS, using human coronary artery endothelial cells in culture. Treatment of cells with (−)-epicatechin led to time- and dose-dependent effects that peaked at 10 minutes at 1 μmol/L. (−)-Epicatechin treatment activates eNOS via serine 633 and serine 1177 phosphorylation and threonine 495 dephosphorylation. Using specific inhibitors, we have established the participation of the phosphatidylinositol 3-kinase pathway in eNOS activation. (−)-Epicatechin induces eNOS uncoupling from caveolin-1 and its association with calmodulin-1, suggesting the involvement of intracellular calcium. These results allowed us to propose that (−)-epicatechin effects may be dependent on actions exerted at the cell membrane level. To test this hypothesis, cells were treated with the phospholipase C inhibitor U73122, which blocked (−)-epicatechin-induced eNOS activation. We also demonstrated inositol phosphate accumulation in (−)-epicatechin-treated cells. The inhibitory effects of the preincubation of cells with the calmodulin-dependent kinase II (CaMKII) inhibitor KN-93 indicate that (−)-epicatechin-induced eNOS activation is at least partially mediated via the Ca/CaMKII pathway. The (−)-epicatechin stereoisomer catechin was only partially able to stimulate nitric oxide production in cells. Together, these results strongly suggest the presence of a cell surface acceptor-effector for the cacao flavanol (−)-epicatechin, which may mediate its cardiovascular effects.
Background
The number of overweight children is increasing at an alarming rate. This issue requires effective action plans, as childhood obesity has become a problem in which addressing environmental ...factors is decisive. Significant differences have also been shown in lifestyle habits that determine overweight based on sex. This study therefore aimed to examine these risk factors according to sex.
Methods
The sample included first‐year high school students from Murcia, Spain. Information was collected through the “Questionnaire on Healthy Habits in Adolescents,” validated for this age range, and the weight, height, and waist circumference of the participants were obtained. Data were analyzed through partial least squares structural equation modeling to determine which modifiable risk factors promoted the appearance of excess weight and in what magnitude.
Results
A total of 421 students participated in the study, and 40.6% of overweight patients were detected according to their body mass index. No differences were found between the sexes and weights. The environment and the use of new technologies that do not involve sitting were significant only in girls (P < 0.05). Conversely, physical activity was significantly higher in boys (P < 0.05). Dietary factors and sedentary activities did not differ according to sex.
Conclusions
The social and school environment, the use of new technologies (for girls), and physical activity (for boys) condition nutritional status. Identifying gender disparities in behaviors that involve health should be a priority for new prevention programs. Targeting young people's health from a gender perspective has considerable potential to reduce overweight problems in adulthood.
Ortega was evaluated to determinate its antihyperglycemic and lipid profile properties. Petroleum ether extract of fresh aerial parts of
(PEfAPSa) and a secondary fraction (F6Sa) were evaluated to ...determine their antihyperglycemic activity in streptozo-cin-induced diabetic (STID) mice, in oral tolerance tests of sucrose, starch, and glucose (OSTT, OStTT, and OGTT, respectively), in terms of glycated hemoglobin (HbA1c), triglycerides (TG), and high-density lipoprotein (HDL). In acute assays at doses of 50 mg/kg body weight (b.w.), PEfAPSa and F6Sa showed a reduction in hyperglycemia in STID mice, at the first and fifth hour after of treatment, respectively, and were comparable with acarbose. In the sub-chronic test, PEfAPSa and F6Sa showed a reduction of glycemia since the first week, and the effect was greater than that of the acarbose control group. In relation to HbA1c, the treatments prevented the increase in HbA1c. In the case of TG and HDL, PEfAPSa and F6Sa showed a reduction in TG and an HDL increase from the second week. OSTT and OStTT showed that PEfAPSa and F6Sa significantly lowered the postprandial peak at 1 h after loading but only in sucrose or starch such as acarbose. The results suggest that
activity may be mediated by the inhibition of disaccharide hydrolysis, which may be associated with an α-glucosidase inhibitory effect.
In an attempt to clarify the controversial role of nitric oxide (NO) in seizures, the effects of NO on brain GABA transaminase (GABA-T) activity and GABA levels were investigated. To this aim, the ...effects of the substrate (
-arginine) and inhibitors (Nω-nitro-
-arginine methyl ester, 7-nitroindazole) of NO synthase (NOS) on GABA-T activity and GABA levels
and
were analyzed.
NO diminished GABA-T activity and increased GABA.
NO modified GABA-T activity and GABA levels biphasically. Inhibition of endothelial and neuronal NOS (eNOS and nNOS) had opposite effects on GABA-T activity and GABA levels, even during seizures induced by pentylenetetrazole. Different effects of NO on GABA-T activity and on GABA levels, depending on the NOS isoform involved, may explain its contradictory role in seizures, the endothelial NOS acting as an anticonvulsant and the neuronal NOS as a proconvulsant. nNOS inhibitors may represent a new generation of antiepileptics.
Non‐technical summary During exercise, skeletal muscle performance depends in great part on the use of aerobic metabolism to supply the energetic demand of contractions. Endurance training increases ...the muscle aerobic capacity, which is not only associated with enhanced exercise performance, but also with a decreased risk of cardiovascular and metabolic diseases. Recently, it has been shown that regular use of small doses of dark chocolate may result in similar health benefits to exercise training. We show here that mice fed for 15 days with (–)‐epicatechin (present in dark chocolate) had improved exercise performance accompanied by: (1) an increased number of capillaries in the hindlimb muscle; and (2) an increased amount of muscle mitochondria as well as signalling for mitochondrial biogenesis. These results suggest that (–)‐epicatechin increases the capacity for muscle aerobic metabolism, thereby delaying the onset of fatigue. These findings may have potential application for clinical populations experiencing muscle fatigue.
The flavanol (–)‐epicatechin, a component of cacao (cocoa), has been shown to have multiple health benefits in humans. Using 1‐year‐old male mice, we examined the effects of 15 days of (–)‐epicatechin treatment and regular exercise on: (1) exercise performance, (2) muscle fatigue, (3) capillarity, and (4) mitochondrial biogenesis in mouse hindlimb and heart muscles. Twenty‐five male mice (C57BL/6N) were randomized into four groups: (1) water, (2) water–exercise (W‐Ex), (3) (–)‐epicatechin ((–)‐Epi), and (4) (–)‐epicatechin–exercise ((–)‐Epi‐Ex). Animals received 1 mg kg−1 of (–)‐epicatechin or water (vehicle) via oral gavage (twice daily). Exercise groups underwent 15 days of treadmill exercise. Significant increases in treadmill performance (∼50%) and enhanced in situ muscle fatigue resistance (∼30%) were observed with (–)‐epicatechin. Components of oxidative phosphorylation complexes, mitofilin, porin, nNOS, p‐nNOS, and Tfam as well as mitochondrial volume and cristae abundance were significantly higher with (–)‐epicatechin treatment for hindlimb and cardiac muscles than exercise alone. In addition, there were significant increases in skeletal muscle capillarity. The combination of (–)‐epicatechin and exercise resulted in further increases in oxidative phosphorylation‐complex proteins, mitofilin, porin and capillarity than (–)‐epicatechin alone. These findings indicate that (–)‐epicatechin alone or in combination with exercise induces an integrated response that includes structural and metabolic changes in skeletal and cardiac muscles resulting in greater endurance capacity. These results, therefore, warrant the further evaluation of the underlying mechanism of action of (–)‐epicatechin and its potential clinical application as an exercise mimetic.
(-)-Epicatechin Is a Biased Ligand of Apelin Receptor Portilla-Martínez, Andrés; Ortiz-Flores, Miguel Ángel; Meaney, Eduardo ...
International journal of molecular sciences,
08/2022, Letnik:
23, Številka:
16
Journal Article
Recenzirano
Odprti dostop
(-)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids and is widely distributed in the plant kingdom. Several studies have shown the beneficial effects of EC consumption. ...Many of these reported effects are exerted by activating the signaling pathways associated with the activation of two specific receptors: the G protein-coupled estrogen receptor (GPER), a transmembrane receptor, and the pregnane X receptor (PXR), which is a nuclear receptor. However, the effects of EC are so diverse that these two receptors cannot describe the complete phenomenon. The apelin receptor or APLNR is classified within the G protein-coupled receptor (GPCR) family, and is capable of activating the G protein canonical pathways and the β-arrestin transducer, which participates in the phenomenon of receptor desensitization and internalization. β-arrestin gained interest in selective pharmacology and mediators of the so-called "biased agonism". With molecular dynamics (MD) and in vitro assays, we demonstrate how EC can recruit the β-arrestin in the active conformation of the APLN receptor acting as a biased agonist.
This study aimed to know the psychometric properties of the five-item Francis scale of the attitude towards Christianity (Francis-5) by assessing psychiatric outpatients in Santa Marta, Colombia. A ...sample of 260 adult patients participated. The exploratory and confirmatory factor analyses revealed an excellent one-dimensional structure with high internal consistency. It was concluded that the Francis-5 exhibited good indicators of validity and reliability in Colombian psychiatric outpatients.
Cardiac fibrosis is one of the hallmarks of a diabetic cardiomyopathy. When activated, cardiac fibroblasts (CFs) increase the production of extracellular matrix proteins. Transforming growth factor ...(TGF)-
1 is known to mediate cardiac fibrosis through the SMAD pathway. High glucose (HG = 25 mM) cell culture media can activate CFs using TGF-
1. There is a need to identify effective antifibrotic agents. Studies in animals indicate that treatment with (-)-epicatechin (Epi) appears capable of reducing myocardial fibrosis. Epi binds to G-protein coupled estrogen receptor (GPER) and activates downstream pathways. We evaluated the potential of Epi to mitigate the development of a profibrotic phenotype in HG stimulated CFs. CF primary cultures were isolated from young male rats and were exposed for up to 48 h HG media and treated with vehicle or 1
M Epi. Relevant profibrotic end points were measured by the use of various biochemical assays. HG exposure of CFs increased TGF-
1 protein levels by ∼15%, fibronectin ∼25%, urea levels ∼60%, proline incorporation ∼70%, and total collagen ∼15%. Epi treatment was able to significantly block HG induced increases in TGF-
1, fibronectin, urea, proline, and total collagen protein levels. GPER levels were reduced by HG and restored in CFs treated with Epi an effect associated with the activation (
, phosphorylation) of c-Src. Epi treatment also reverted SMAD levels. Altogether, results demonstrate that CFs cultured in HG acquire a profibrotic phenotype, which is blocked by Epi an effect, likely mediated at least, in part, by GPER effects on the SMAD/TGF-
1 pathway.
Objective
To establish the association between quality of life and depression among COPD patients of the Colombian Caribbean.
Method
A cross‐sectional study was carried out with the participation of ...adult COPD patients. COPD‐related quality of life was quantified with the COPD Assessment Test (CAT) and depression using the Zung 10‐item Self‐rating Depression Scale (SDS‐10). The relationship between COPD‐related quality of life and depression with odds ratios (OR), crude and adjusted, was determined.
Results
408 patients participated in the study. They were aged between 40 and 102 years (mean = 72.9, SD = 10.2) and 58.8% men. Two hundred eighty‐four patients (69.6%) reported worse health status (CAT ≥10), and 114 patients (27.9%) scored for depression (SDS‐10). Patients with worse health status presented more depression (OR = 5.85, 95% CI 3.01–11.36) and after adjusting for gender (OR = 5.70, 95% CI 2.92–11.13).
Conclusions
In patients with COPD and CAT ≥10, there is a five times greater risk of depression than patients with CAT <10. However, the relationship may be bidirectional. It is essential to specify the direction of causality in future investigations.
The role of the energy industry has always been central for one reason or another, being environmentalism the main motive in the last two decades. Therefore, attention and research have been directed ...in this sense. However, human resources—or human capital—have remained understudied, especially concerning the salaries received. Thus, this study is disruptive as it explored the factors that influence employee remuneration in the energy subsector, using Spain as a case study. For this, the PLS-SEM (Partial Least Squares Structural Equation Modelling) path modelling methodology was used, executing a traditional PLS analysis, bootstrapping and, finally, IPMA (Importance-Performance Analysis). Solid and significant relationships were found among labour conditions, human capital, market and wages, with the relationships between human capital and wages and between human capital and labour conditions being especially relevant. Besides, through IPMA, a series of considerations was made regarding the individual indicators according to their relative importance and performance. Consequently, this paper significantly contributes to the extant literature by analysing the composition of wages in the energy sector, which might allow taking valuable management decisions. Nevertheless, the main limitation of this study lies in the availability of data for Spain and, specifically, for workers in the energy supplying industries.
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