Breast cancer, due to its high incidence and mortality, is a public health problem worldwide. Current chemotherapy uses non-specific cytotoxic drugs, which inhibit tumor growth but cause significant ...adverse effects. (−)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids. It is widely distributed in the plant kingdom; it can be found in green tea, grapes, and cocoa. Several studies in animals and humans have shown that EC induces beneficial effects in the skeletal muscle and the cardiovascular system, reducing risk factors such as arterial hypertension, endothelial dysfunction, damage to skeletal muscle structure, and mitochondrial malfunction by promoting mitochondrial biogenesis, with no adverse effects reported. Recently, we reported that EC had an antitumor effect in a murine triple-negative mammary gland tumor model, decreasing tumoral size and volume and increasing survival by 44%. This work aimed to characterize the effects of flavanol EC on proliferation, migration, and metastasis markers of triple-negative murine breast (4T1) cancer cells in culture. We found proliferation diminished and Bax/Bcl2 ratio increased. When the migration of culture cells was evaluated, we observed a significant reduction in migration. Also, the relative expression of the genes associated with metastasis, Cdh1, Mtss1, Pten, Bmrs, Fat1, and Smad4, was increased. In conclusion, these results contribute to understanding molecular mechanisms activated by EC that can inhibit metastatic-associated proliferation, migration, and invasion of murine breast cancer cells.
(-)-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.
Age-adjusted rates of cardiovascular disease (CVD) are higher in men than in women. CVD risk-factor outcomes are underrecognized, underestimated, and undertreated in women because the clinical ...expressions in women differ from those of men. There are no universally accepted recommendations on what to do in women when the values of fasting glucose, blood pressure, and lipids are only slightly altered or at borderline values. We reported the positive effects on CVD risk markers using cacao by-products, showing that alternative approaches can be used to prevent cardiovascular disease in women. The objective was to evaluate the changes in lipoprotein subfractions induced by three months of treatment with an epicatechin-enriched cacao supplement.
A double-blind, placebo-controlled proof-of-concept study was developed to evaluate the effects of 3 months of treatment with an (-)-epicatechin-enriched cacao supplement on lipoprotein subfractions.
The usual screening workshop for postmenopausal women could be insufficient and misleading. Assessing the effect of a (-)-epicatechin-enriched cacao supplement employing a lipoprotein subfractionation profile analysis suggests a decrease in cardiovascular risk.
A simple, low-cost, safe (-)-epicatechin-enriched cacao supplement product can improve the cardiovascular risk in postmenopausal women.
An inflammation response occurs when the body reacts to exogenous and endo enous noxious stimuli, and it helps the body respond to infection and repair tissues, adapt to stress, and remove dead or ...damaged cells. Anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs are traditionally used to treat inflammation; however, these drugs often cause negative side effects. For this reason, developing and establishing effective alternative medicines for treating many chronic diseases with underlying inflammation is critically dependent on the identification of new organic molecules and bioactive substances. Aromatic and volatile compounds found in essential oils isolated from Pimenta dioica (allspice), Cuminum cyminum (cumin), and Citrus sinensis (sweet orange) are a source of bioactive compounds. Allspice essential oil reduces ear inflammation more than 65% and the anti-inflammatory activity of allspice essential oil is enhanced when combined with sweet orange peel and cumin essential oils, resulting in the reduction of edema inflammation by more than 85%, similar to indomethacin. As an alternative to anti-inflammatory treatment, essential oil mix is pharmacologically safe as it is neither toxic nor mutagenic.
The production of nitric oxide (NO) by nitric oxide synthases (NOS) depends on the bioavailability of L-arginine as NOS competes with arginase for this common substrate. As arginase activity ...increases, less NO is produced and adverse cardiovascular consequences can emerge. (-)-Epicatechin (EPI), the most abundant flavonoid in cacao, has been reported to stimulate endothelial and neuronal NOS expression and function leading to enhanced vascular function and cardioprotective effects. However, little is known about the effects of EPI on myocardial arginase activity. The aim of the present study was to determine if EPI is able to interact and modulate myocardial arginase and NOS expression and activity. For this purpose, in silico modeling, in vitro activity assays and a rat model of ischemia/reperfusion injury were used. In silico and in vitro results demonstrate that EPI can interact with arginase and significantly decrease its activity. In vivo, 10 days of EPI pretreatment reduces ischemic myocardium arginase expression while increasing NOS expression and phosphorylation levels. Altogether, these results may partially account for the cardioprotective effects of EPI.
Pediatric astrocytomas, a leading cause of death associated with cancer, are the most common primary central nervous system tumors found in children. Most studies of these tumors focus on adults, not ...on children. We examined the global protein and microRNA expression pattern by 2D SDS-PAGE, mass spectrometry (MALDI-TOF), and RT2 miRNA PCR Array System. Proteomic studies revealed 49 proteins with changes on the expression. Interactome showed that vimentin, calreticulin, and 14-3-3 epsilon protein are hub proteins in these neoplasms. MicroRNA analyses demonstrated for the first time novel microRNAs involved in the astrocytoma biology. In conclusion, our results show that novel proteins and microRNAs with expression changes on pediatric astrocytoma could serve as biomarkers of tumor progression.
Astrocytomas are tumors that progress rapidly and that invade surrounding tissues. Although some drugs have been developed to treat these neoplasms, the mortality of patients is still very high. In this study, we describe for the first time, to our knowledge, some proteins and miRNAs associated with the biology of astrocytic tumors that could be postulated as possible diagnostic or prognostic biomarkers. Altogether, our results indicate that large-scale analyses allow making a fairly accurate prediction of different cellular processes altered in astrocytic tumors.
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•Forty nine proteins with expression changes in pediatric astrocytomas are reported.•Calreticulin, vimentin, and 1433 epsilon protein are possible hub proteins.•Novel microRNAs, involved in astrocytoma biology, are revealed for the first time.•Altered proteins and microRNAs are involved in the same signaling pathways.•Some protein changes appear to correlate with microRNA alteration.
Here, we report for the first time the circulation of dengue virus type 1 (DENV-1) belonging to the lineage IV of genotype V (African American genotype) based on phylogenetic analysis of nucleotide ...sequences from 10 DENV-1-positive samples obtained in Mexico between 2012 and 2014. Our data revealed that the lineages III and IV of DENV-1 genotype V were found circulating during the same period, probably explaining the rise in the number of cases of severe dengue during that period.
Se analizan los patrones de localización espacial de los diferentes sectores que componen las manufacturas mexicanas sobre un espacio continuo. Se hace utilizando la función K de Ripley, técnica ...basada en la distancia que permite tratar el espacio como continuo. Al utilizar como referencia la CSR (Complete Spatial Randomnes) se encontraron concentraciones espaciales significativas para todos los sectores manufactureros a diferentes rangos de distancia. Asimismo, se detectó que la estructura espacial de las manufacturas es bimodal. Sin embargo, al usar la distribución espacial del conjunto de las manufacturas como punto de referencia se han obtenido variaciones en la distribución espacial.
This research explores spatial location patterns of firms in different sectors of the Mexican manufacturing. The analysis is carried under a continuous spatial statistic approach by employing a K-function for each sector that is then compared to a CSR distribution (Complete Spatial Randomness) and other relevant benchmarks. It has been found that manufacturing follows a bimodal distribution and where spatial concentrations at different distances for each of the manufacturing sectors are present. However, using the spatial distribution of the set of manufactures as a point of reference, variations in the spatial distribution have been obtained.
: The Mexican population exhibits several cardiovascular risk factors (CVRF) including high blood pressure (HBP), dysglycemia, dyslipidemia, overweight, and obesity. This study is an extensive ...observation of the most important CVFRs in six of the most populated cities in Mexico.
: In a cohort of 297,370 participants (54% female, mean age 43 ± 12.6 years), anthropometric (body mass index (BMI)), metabolic (glycemia and total cholesterol (TC)), and blood pressure (BP) data were obtained.
: From age 40, 40% and 30% of the cohort's participants were overweight or obese, respectively. HBP was found in 27% of participants. However, only 8% of all hypertensive patients were controlled. Fifty percent of the subjects 50 years and older were hypercholesterolemic. Glycemia had a constant linear relation with age. BMI had a linear correlation with SBP, glycemia, and TC, with elevated coefficients in all cases and genders. The β1 coefficient for BMI was more significant in all equations than the other β, indicating that it greatly influences the other CVRFs.
: TC, glycemia, and SBP, the most critical atherogenic factors, are directly related to BMI.
Nitrogen-doped graphitic nanoribbons are synthesized by a single-step chemical vapor deposition method using pyrazine as the nitrogen source. As M. Terrones and co-workers report , the morphology of ...the nanoribbons is correlated to the presence of N atoms within the graphitic structure. Spectroscopy results, in conjunction with transport measurements on individual nanoribbons and DFT theoretical simulations, indicate that nitrogendoped graphitic nanoribbons possess features that are potentially useful for the development of sensors and other electronic components.
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