Cardiac aging is characterized by alterations in contractility and intracellular calcium (Ca
) homeostasis. It has been suggested that oxidative stress may be involved in this process. We and others ...have reported that in cardiomyopathies the NADPH oxidase (NOX)-derived superoxide is increased, with a negative impact on Ca
and contractility. We tested the hypothesis that in the aged heart, Ca
handling and contractility are disturbed by NOX-derived superoxide. For this we used adults (≈5 month-old) and aged (20⁻24 month-old) rats. Contractility was evaluated in isolated hearts, challenged with isoproterenol. To assess Ca
, isolated cardiac myocytes were field-stimulated and Ca
was monitored with fura-2. Cardiac concentration-response to isoproterenol was depressed in aged compared to adults hearts (
< 0.005), but was restored by NOX inhibitors apocynin and VAS2870. In isolated cardiomyocytes, apocynin increased the amplitude of Ca
in aged myocytes (
< 0.05). Time-50 Ca
decay was increased in aged myocytes (
< 0.05) and reduced towards normal by NOX inhibition. In addition, we found that myofilaments Ca
sensitivity was reduced in aged myocytes (
< 0.05), and was further reduced by apocynin. NOX2 expression along with NADPH oxidase activity was increased in aged hearts. Phospholamban phosphorylation (Ser16/Thr17) after isoproterenol treatment was reduced in aged hearts compared to adults and was restored by apocynin treatment (
< 0.05). In conclusion, β-adrenergic-induced contractility was depressed in aged hearts, and NOX inhibition restored back to normal. Moreover, altered Ca
handling in aged myocytes was also improved by NOX inhibition. These results suggest a NOX-dependent effect in aged myocytes at the level of Ca
handling proteins and myofilaments.
The genera and species of Chilean rhagionids (Diptera: Rhagionidae) are listed, with annotated references to nomenclature, synonymies and generic combinations, type localities, the primary type ...depositories, distribution, and citations for the most recent revisions. The genus Atherimorpha White is the richest genus in Chile, with 15 described species. Only Leptis basalis Philippi, 1865 is kept as incertae sedis in the family.
Adiponectin is thought to play a decisive role in the relationships among obesity, insulin resistance and cardiovascular risk. This study investigated whether cardiomyocytes synthesize and secrete ...adiponectin, and the effects of this hormone on cardiac cells. RT-PCR showed that mouse, rat and human cardiomyocytes produced mRNA for adiponectin and adiponectin receptors 1 and 2. Immunohistochemistry confirmed the presence of adiponectin in the cytoplasm of cultured cardiomyocytes, and radioimmunoassay showed that these cells secreted adiponectin into the culture medium. Exogenous adiponectin enhanced glucose and fatty acid uptake and induced AMPK phosphorylation in cultured cardiomyocytes. Our results demonstrate that adiponectin is synthesized and secreted by isolated murine and human cardiomyocytes, and suggest that the local production of this hormone by cardiomyocytes could be involved in the regulation of cardiac metabolism and function.
Low-grade chronic inflammation plays a pivotal role among other pathophysiological mechanisms involved in obesity. Innate and adaptive immune cells undergo systemic proinflammatory polarization that ...gives rise to an increased secretion of proinflammatory cytokines, which in turn leads to insulin resistance. Bariatric surgery is currently the most effective treatment for obesity, as it brings on significant weight loss, glucose metabolism improvement, and a decrease in systemic inflammation biomarkers. After bariatric surgery, several changes have been reported to occur in adaptive immunity, including reduction in CD4+ and CD8+ T cell counts, a decrease in the Th1/Th2 ratio, an increase in B regulatory cells, and reduction in proinflammatory cytokine secretion. Overall, there seems to be a major shift in several lymphocyte populations from a proinflammatory to an anti-inflammatory phenotype. Furthermore, increased antioxidant activity and reduced lipid and DNA oxidation products have been reported after bariatric surgery in circulating mononuclear cells. This paper highlights the shift in the adaptive immune system in response to weight loss and improved insulin sensitivity, as well as the interplay between immunological and metabolic adaptations as a result of bariatric surgery. Finally, based on data from research, we propose several mechanisms such as changes in adaptive immune cell phenotypes and their by-products, recruitment in adipose tissue, reduced oxidative stress, and modification in metabolic substrate availability as drivers to reduce low-grade chronic inflammation after bariatric surgery in severe obesity.
Sigma-1 receptor antagonists promote antinociception in several models of pain, but the effects of sigma-1 agonists on nociception (particularly when the nociceptive system is primed) are not so well ...characterized; therefore we evaluated the effects of sigma-1 agonists on pain under different experimental conditions. The systemic administration of the selective sigma-1 agonists (+)-pentazocine and PRE-084, as well as the nonselective sigma-1 agonist carbetapentane (used clinically as an antitussive drug), did not alter sensitivity to mechanical stimulation under baseline conditions. However, they greatly promoted secondary mechanical allodynia after priming the nociceptive system with capsaicin. These effects of sigma-1 agonists were consistent in terms potency with the affinities of these drugs for sigma-1 receptors, were reversed by sigma-1 antagonists, and were not observed in sigma-1 knockout mice, indicating that they are sigma-1-mediated. Repeated systemic treatment with PRE-084 induced proallodynic effects even 24 h after treatment completion, but only after the nociceptive system was primed. However, neither the presence of this drug in the organism nor changes in sigma-1 receptor expression in areas involved in pain processing explains its long-term effects, suggesting that sustained sigma-1 agonism induces plastic changes in the nociceptive system that promote nociception.
Essentials
Estrogens are known to influence the expression of microRNAs in breast cancer cells.
We looked at microRNAs in estrogenic regulation of tissue factor pathway inhibitor α (TFPIα).
Estrogen ...upregulated microRNA‐27a/b and microRNA‐494 through the estrogen receptor α.
MicroRNA‐27a/b and microRNA‐494 are partly involved in estrogenic downregulation of TFPIα.
Summary
Background
Tissue factor pathway inhibitor (TFPI) has been linked to breast cancer pathogenesis. We have recently reported TFPI mRNA levels to be downregulated by estrogens in a breast cancer cell line (MCF7) through the estrogen receptor α (ERα). Accumulating evidence also indicates that activation of ERα signaling by estrogens may modulate the expression of target genes indirectly through microRNAs (miRNAs).
Objectives
To examine if miRNAs are involved in the estrogenic downregulation of TFPIα.
Methods
Computational analysis of the TFPI 3′‐untranslated region (UTR) identified potential binding sites for miR‐19a/b, miR‐27a/b, miR‐494, and miR‐24. Transient overexpression or inhibition of the respective miRNAs was achieved by transfection of miRNA mimics or inhibitors. Direct targeting of TFPI 3′‐UTR by miR‐27a/b and miR‐494 was determined by luciferase reporter assay in HEK293T cells. Effects of 17α‐ethinylestradiol (EE2) and fulvestrant on relative miR‐27a/b, miR‐494, and TFPI mRNA levels in MCF7 cells were determined by qRT‐PCR and secreted TFPIα protein by ELISA. Transient knockdown of ERα was achieved by siRNA transfection.
Results
EE2 treatment lead to a significant increase in miR‐19a, miR‐27a/b, miR‐494, and miR‐24 mRNA levels in MCF7 cells through ERα. miR‐27a/b and miR‐494 mimics lead to reduced TFPI mRNA and protein levels. Luciferase assay showed direct targeting of miR‐27a/b and miR‐494 on TFPI mRNA. Impaired estrogen‐mediated downregulation of TFPI mRNA was detected in anti–miR‐27a/b and anti–miR‐494 transfected cells.
Conclusions
Our results provide evidence that miR‐27a/b and miR‐494 regulate TFPIα expression and suggest a possible role of these miRNAs in the estrogen‐mediated downregulation of TFPIα.
The Homalocnemidae of Chile is reviewed, including the descriptions of the male and female terminalia of the two known species: H. nigripennis Philippi and H. praesumpta Collin. All references ...pertaining to Chilean Homalocnemis Philippi and the two known species are provided. Geographical distributions of the species were compiled and mapped from bibliographic data and collections. An illustrated key to the two species is also presented.
Ethanol intake during pregnancy can produce a wide range of adverse effects on nervous system development including fetal alcohol syndrome (FAS). The most severe congenital malformation observed in ...newborns with FAS is cyclopia. In this study, we have exposed zebrafish embryos to different ethanol concentrations (2.4%, 1.5% or 1.0%) during eye morphogenesis in four zebrafish strains (AB, EK, GL and TL). In addition, we have studied the survival rate of the cyclopic animals to the end of larval development.
The zebrafish strains GL and AB generated the higher percentage of cyclopic animals after exposure to 2.4% ethanol, while EK showed the higher percent cyclopic animals using 1.5% and 1.0% ethanol. The EK strain showed the higher percent survival during the larval period at all ethanol concentrations (2.4%, 1.5% and 1.0%). Moreover, we have investigated cytoarchitectural alterations in the main components of the visual pathway–retina and optic tectum–and ethanol treatment affects both the retina and the optic tectum. The lamination of neural retina is clearly delayed in treated larvae 3 days postfertilization and the thickness of the pigmented epithelium is considerably reduced. With regard to the optic tectum, treatment with ethanol alters the normal pattern of tectal lamination. The use of zebrafish EK strain is a suitable in vivo vertebrate model system for analyzing the teratogenic effect of ethanol during vertebrate visual system morphogenesis as it relates to both cyclopia and FAS.
In addition to sample solubility constraints, the use of polarity gradients in normal-phase centrifugal partition chromatography (CPC) for the purification of complex mixtures is also limited by the ...instability of biphasic systems as a consequence of dramatic changes in the settling times along the gradient, leading in many cases to column bleeding when working under maximum efficiency conditions. In this paper an electrostriction approach is proposed as a strategy in reversed-phase CPC to fractionate intermediate polarity extracts in a single run by bringing its components into the “sweet spot” in a controlled fashion through a stepwise reduction of salt concentration in the aqueous mobile phase. The salting-out gradient method was successfully tested with the separation of the major chlorogenic acids (CGAs, hydroxycinnamoylquinic acids) present in green coffee beans (5-caffeoylquinic acid (5-CQA), 5-feruloylquinic acid (5-FQA) and 3,5-dicaffeoylquinic acid (3,5-diCQA)) using ethyl acetate-hexane as the stationary phase and an ionic gradient of LiCl (5.0, 2.5 and 0.1
M) as the mobile phase in one case and (NH
4)
2SO
4/KNO
3 (3.0 and 1.5
M/1.5
M) in another. Regioisomers of each chlorogenic acid obtained by base-catalyzed isomerisation were also separated by CPC using isocratic elution. The best resolution for both FQAs and diCQAs was achieved with a chloroform–
n-butanol–0.01
M pH 2.5 phosphate buffer (84:16:100; v/v) system, while CQAs were best isolated using chloroform–
n-butanol–0.01
M pH 2.5 phosphate buffer/5.0
M LiCl (82:18:100; v/v).
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