Major depressive disorder (MDD) is one of the most disabling disorders and the one that most contributes to disability. When it occurs in older people, it is an additional burden to their potential ...physical and cognitive deficiencies, making MDD an important public health problem that supposes a large investment in health. There is a clear lack of consistency between the subtypes of depression found in the literature, ranging from two to seven classes, with three being the most commonly found non-melancholic, melancholic and psychotic, or putative psychotics. The aim of this research is to add knowledge to the profiles of depressive symptoms in a representative sample of older Spanish people, and to study the possible relationship of these symptom profiles with variables that have traditionally been related to depression. Spanish data from the sixth wave of SHARE were used, with 612 Spanish older adults living in Spain. A routine of several LCAs with a different number of classes was performed to answer this first aim to classify Spanish adults with depression symptoms. The results pointed out the presence of three different classes among the participants in the study: psychosomatic (11.12%), melancholic (14.21%), and anhedonic (74.67%). This work represents a step forward to understand the heterogeneity of major depressive disorder, facilitating the diagnosis, and subsequent treatment of older adults.
Sunflower oil was heated at 190°C in a discontinuous industrial fryer for 32h. The simultaneous monitoring during heating of the Iodine Value, acyl groups proportions and aldehydes concentrations was ...carried out by 1H Nuclear Magnetic Resonance; at the same time the percentage in weight of Polar Compounds was also controlled by an instrumental test. The evolution with heating time of Iodine value, percentage in weight of polar compound and acyl groups proportions fit well to linear equations. The formation of primary oxidation compounds was not observed in contrast with the early detection of different types of aldehydes such as alkanals, (E)-2-alkenals, (E,E)-2,4-alkadienals, (Z,E)-2,4-alkadienals, 4-oxoalkanals and the genotoxic and citotoxic 4-hydroxy-(E)-2-alkenals; their evolution with heating time fits well to curved lines in most cases. The results obtained were compared with those previously obtained in a domestic fryer, resulting in clearly higher degradation rate of acyl groups in the domestic fryer than in the industrial one; however, the differences in aldehydes concentration were less remarkable due to the higher retention degree of aldehydes in the industrial version. Aldehydes retention was shown to be directly related with oil volume and inversely to the oil–air surface and aldehyde volatilities. The presence of the genotoxic and citotoxic 4-hydroxy-(E)-2-alkenals from the beginning of the sunflower oil heating is cause of concern for the human health. The concentration of aldehydes when the oil reaches 25% in weight of polar compounds is near its maximum values. These results suggest the need to analyze in depth the safety of some oils when they are submitted to heating at frying temperature.
► Sunflower oil was heated at 190 °C in an industrial fryer for 32 hours. ► Parameters of oil quality and safety were determined simultaneously from 1H NMR data. ► Equations that relate parameter values and heating time were obtained. ► Results were compared with those obtained in a domestic fryer. ► The presence of toxic aldehydes in the heated sunflower oil is cause of concern.
Pro-environmental behavioral patterns are influenced by relevant others’ actions and expectations. Studies about the intergenerational transmission of environmentalism have demonstrated that parents ...play a major role in their children’s pro-environmental actions. However, little is known about how other social agents may shape youth’s environmentalism. This cross-sectional study concentrates on the role that parents and peers have in the regulation of 12- to 19-year-olds’ pro-environmental behaviors. We also consider the common response bias effect by examining the associations between parents, peers, and adolescents’ pro-environmentalism in two independent data sets. Data Set 1 (N = 330) includes adolescents’ perceptions of relevant others’ behaviors. Data Set 2 (N = 152) includes relevant others’ self-reported pro-environmental behavior. Our results show that parents’ and peers’ descriptive and injunctive norms have a direct effect on adolescents’ pro-environmental behavior and an indirect one, through personal norms. Adolescents seem to be accurate in the perception of their close ones’ environmental actions.
Treatment for 14 to 24 hours with low concentrations of arsenic trioxide (As2O3, 1-4 μM) caused apoptosis in U-937 promonocytes and other human myeloid leukemia cell lines (HL-60, NB4). This effect ...was potentiated by cotreatment with the phosphatidylinositol 3-kinase (PI3K) inhibitors LY294002 and wortmannin, and the Akt inhibitor Akti5. However, the inhibitors did not increase the toxicity of the mitochondria-targeting drug lonidamine, and the DNA-specific drugs camptothecin and cisplatin, when used under similar experimental conditions as As2O3. The potentiation of As2O3-provoked apoptosis involved the increased disruption of mitochondrial transmembrane potential, increased caspase-3 activation and cytochrome c release from mitochondria, increased Bax and Bid activation, and attenuation of 27-kDa heat shock protein (HSP27) expression; the potentiation was prevented by Bcl-2 overexpression. The PI3K/Akt inhibitors decreased the intracellular glutathione content, and caused intracellular oxidation, as measured by peroxide accumulation. Cotreatment with subcytotoxic concentrations of hydrogen peroxide increased apoptosis induction by As2O3. On the other hand, the treatments did not significantly affect glutathione S-transferase π expression and activity. These results, which indicate that glutathione is a target of PI3K/Akt in myeloid leukemia cells, may partially explain the selective increase of As2O3 toxicity by PI3K/Akt inhibitors, and may provide a rationale to improve the efficacy of these inhibitors as therapeutic agents.
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related death. Different signaling pathways are de-regulated in this pathogenesis, among them the epidermal growth factor ...receptor one (EGFR/Erb1). Here we show that blockage of this pathway by the tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG1478) in different liver tumor cell lines promotes both inhibition of cell proliferation and induction of cell death, which are coincident with arrest in the G1 phase of the cell cycle, caspase-3 activation and DNA fragmentation. AG1478 up-regulates the expression of the pro-apoptotic member of the BCL-2 family BIM and down-regulates the expression of the anti-apoptotic BCL-XL and MCL1. Furthermore, it also decreases the levels of the caspase inhibitors HIAP2 and XIAP. The treatment of HCC cells with AG1478 enhanced the apoptosis induced by other pro-apoptotic stimuli, such as the physiological cytokine, TGF-β, highly expressed in liver tumors, or the chemotherapeutic drug doxorubicin. The effects observed by AG1478 were broader than the ones seen by silencing of the EGFR with siRNA, which indicates that this drug might act on other targets different from the EGFR. In this same line of evidence, AG1478 retained some cytotoxic effects in cells where EGFR has been targeted knock-down with shRNA. Interestingly, AG1478 preferentially acts on liver tumor cells, being untransformed cells much less responsive to its cytotoxic effects. In conclusion, AG1478 could be a potential therapeutic drug to be used in HCC.
Liver tumor cells show several molecular alterations which favor pro-survival signaling. Among those, we have proposed the NADPH oxidase NOX1 as a prosurvival signal for liver tumor cells. On the one ...side, we have described that FaO rat hepatoma cells show NOX1-dependent partial resistance to apoptosis induced by Transforming Growth Factor beta (TGF-β). On the other side, we have shown that FaO cells, as well as different human hepatocellular carcinoma (HCC) cell lines, are able to proliferate in the absence of serum through the activation of a NOX1-dependent signaling pathway. The aim of this work was to analyze the effects of NADPH oxidase pharmacological inhibition in liver tumor cells using the inhibitor VAS2870. This compound inhibits dose-dependently autocrine increase of cell number in FaO rat hepatoma cells, and almost completely blocked ROS production and thymidine incorporation when used at 25
μM. Such inhibitory effect on autocrine growth is coincident with lower mRNA levels of EGFR (Epidermal Growth Factor Receptor) and its ligand TGF-α (Transforming Growth Factor-alpha), and decreased phosphorylation of the EGFR itself and other downstream targets, such as SRC or AKT. Moreover, NADPH oxidase pharmacological inhibition also effectively attenuates serum-dependent growth and phosphorylation of AKT and ERK. Importantly, these inhibitory effects on either autocrine or serum-dependent cell growth are observed in several human HCC cell lines. Finally, we have observed that VAS2870 is also effective in enhancing apoptosis induced by a physiological stimulus, such as TGF-β. In summary, NADPH oxidase pharmacological inhibition could be considered a promising tool in the treatment of liver cancer.
Chemoresistance constitute nowadays the major contributor to therapy failure in most cancers. There are main factors that mitigate cell response to therapy, such as target organ, inherent sensitivity ...to the administered compound, its metabolism, drug efflux and influx or alterations on specific cellular targets, among others. We now know that intrinsic properties of cancer cells, including metabolic features, substantially contribute to chemoresistance. In fact, during the last years, numerous reports indicate that cancer cells resistant to chemotherapy demonstrate significant alterations in mitochondrial metabolism, membrane polarization and mass. Metabolic activity and expression of several mitochondrial proteins are modulated under treatment to cope with stress, making these organelles central players in the development of resistance to therapies. Here, we review the role of mitochondria in chemoresistant cells in terms of metabolic rewiring and function of key mitochondria-related proteins.