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The endoplasmic reticulum maintains proteostasis, which can be disrupted by oxidative stress, nutrient deprivation, hypoxia, lack of ATP, and toxicity caused by xenobiotic compounds, all of which can result in the accumulation of misfolded proteins. These stressors activate the unfolded protein response (UPR), which aims to restore proteostasis and avoid cell death. However, endoplasmic response-associated degradation (ERAD) is sometimes triggered to degrade the misfolded and unassembled proteins instead. If stress persists, cells activate three sensors: PERK, IRE-1, and ATF6. Glioma cells can use these sensors to remain unresponsive to chemotherapeutic treatments. In such cases, the activation of ATF4 via PERK and some proteins via IRE-1 can promote several types of cell death. The search for new antitumor compounds that can successfully and directly induce an endoplasmic reticulum stress response ranges from ligands to oxygen-dependent metabolic pathways in the cell capable of activating cell death pathways. Herein, we discuss the importance of the ER stress mechanism in glioma and likely therapeutic targets within the UPR pathway, as well as chemicals, pharmaceutical compounds, and natural derivatives of potential use against gliomas.
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Estresse do Retículo Endoplasmático , Glioma , Humanos , Resposta a Proteínas não Dobradas , Retículo Endoplasmático , Glioma/tratamento farmacológico , Preparações FarmacêuticasRESUMO
This article provides an overview of the current landscape and needs for education in emergencies, as well as challenges and opportunities in today's critical juncture, in particular with the creation of a new ally for education in emergencies: the Geneva Global Hub for Education in Emergencies. It covers the disruption of education by the Covid-19 pandemic and the associated exacerbation of child-protection risks, as well as the pandemic's impact on the realization of the right to education of displaced children and youth and those living in humanitarian crises. While there is ample recognition at the international policy level of the importance of education in emergencies, major obstacles still prevail, such as continued underfunding and the underprioritization of education in humanitarian situations. As the world faces unparalleled needs, in particular during crises, and grapples to accelerate progress toward Sustainable Development Goal 4 and meet the commitments set out in the Global Compact for Refugees, new opportunities promise to tap opportune alliances, to inspire commitment, and to boost country-level impact.
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The control principle implies that people should not feel guilt for outcomes beyond their control. Yet, the so-called 'agent and observer puzzles' in philosophy demonstrate that people waver in their commitment to the control principle when reflecting on accidental outcomes. In the context of car accidents involving conventional or autonomous vehicles (AVs), Study 1 established that judgments of responsibility are most strongly associated with expressions of guilt-over and above other negative emotions, such as sadness, remorse or anger. Studies 2 and 3 then confirmed that, while people generally endorse the control principle, and deny that occupants in an AV should feel guilt when involved in an accident, they nevertheless ascribe guilt to those same occupants. Study 3 also uncovered novel implications of the observer puzzle in the legal context: Passengers in an AV were seen as more legally liable than either passengers in a conventional vehicle, or even their drivers-especially when participants were prompted to reflect on the passengers' affective experience of guilt. Our findings document an important conflict-in the context of AV accidents-between people's prescriptive reasoning about responsibility and guilt on one hand, and their counter-normative experience of guilt on the other, with apparent implications for liability decisions.
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Veículos Autônomos , Culpa , Acidentes de Trânsito , Emoções , Humanos , Comportamento SocialRESUMO
PURPOSE: Medulloblastoma is an embryonal brain tumor that predominantly occurs in childhood with a wide histological and molecular variability. Our aim was to investigate the expression of Toll-like receptors (TLRs), their association with the infiltration of immune cells and with the histological subgroups, and, also, with the overall survival of patients. METHODS: Fifty-six paraffin-preserved biopsies from children with medulloblastoma of the classic, desmoplastic, and anaplastic subtypes were included. Microarrays of tissues were performed, and the infiltration of T and NK cells was quantified, as well as the expression of TLR7, TLR8, and TLR9. For all statistical analyses, significance was p < 0.05. RESULTS: CD4 + and CD8 + T lymphocytes and NK cells were found infiltrating the tumor. The infiltration of NK and CD4 + cells was greater in the classic and desmoplastic subtypes than in anaplastic. We found an important expression of TLRs in all medulloblastomas, but TLR7 and TLR8 were considerably higher in classic and desmoplastic subtypes than in anaplastic. Importantly, we observed that TLR7 was a prognostic factor for survival. CONCLUSIONS: Medulloblastomas present cellular infiltration and a differential expression of TLRs depending on the histological subtype. TLR7 is a prognostic factor of survival that is dependent on treatment and age.
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Neoplasias Encefálicas , Neoplasias Cerebelares , Meduloblastoma , Receptor 7 Toll-Like/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Cerebelares/diagnóstico , Criança , Humanos , Meduloblastoma/diagnóstico , Taxa de Sobrevida , Receptor 8 Toll-LikeRESUMO
PURPOSE: MicroRNAs were identified as molecules that participate in gene regulation; alterations in their expression characterize central nervous system (CNS). Information in pediatrics is scarce, so the objective of this work was to determine and then compare the patterns of expression of microRNAs in astrocytomas, ependymomas, and medulloblastomas, as well as in non-neoplastic brain. METHODS: Low-density arrays were utilized to evaluate 756 microRNAs in three samples of each type of tumor and non-neoplastic brain. The relative expression was calculated in order to identify the three microRNAs whose expression was modified notably. This was verified using RT-qPCR in more number of tumor samples. RESULTS: The microRNAs selected for testing were miR-100-5p, miR-195-5p, and miR-770-5p. A higher expression of miR-100-5p was observed in the astrocytomas and ependymomas compared to the medulloblastomas: on average 3.8 times (p < 0.05). MiR-770-5p was expressed less in medulloblastomas compared to astrocytomas four times (p = 0.0162). MiR-195-5p had a low expression in medulloblastomas compared to non-neoplastic cerebellum (p = 0.049). In all three tumor types, expression of miR-770-5p was lower than in non-neoplastic brain (p < 0.001). CONCLUSIONS: These microRNAs may represent potential markers in these tumors.
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Biomarcadores Tumorais/biossíntese , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/biossíntese , Adolescente , Biomarcadores Tumorais/genética , Neoplasias do Sistema Nervoso Central/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , México/epidemiologia , MicroRNAs/genéticaRESUMO
PURPOSE: A 10-month-old girl with a Brachmann-Cornelia de Lange syndrome and a choroid plexus papilloma of the brain was studied at the Hospital Infantil de México Federico Gómez (HIMFG) in Mexico City. METHODS AND RESULTS: Presumptive papilloma of the third ventricle was evidenced on CT and MR images and removed. Pathological analysis confirmed its origin. A posterior radiosurgery was required due to a tumor relapse. Karyotypes (GTG bands) of the patient and her parents undertaken at HIMFG were normal. Array comparative genomic hybridization (array CGH) analyses of blood DNA of the patient and her parents carried out at BlueGnome's Laboratory in Cambridge, UK, set in evidence amplification of genes SPNS2, GGT6, SMTNL2, PELP1, MYBBP1A, and ALOX15 in chromosome 17p of the patient. Since MYBBP1A is a proto-oncogene and ALOX15 participates in the development of cancer and metastases of tumors, further fluorescent in situ hybridization (FISH) analyses of these two genes were implemented at HIMFG. Amplification of the two genes was found in the tumor of the case under study but not in an unrelated papilloma of the choroid plexus. DISCUSSION: Further analyses of the association of choroid plexus papillomas with disorders of psycho-neural development and its relationship to molecular genetic modifications at chromosome 17p are now under way at HIMFG.
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Síndrome de Cornélia de Lange/complicações , Papiloma do Plexo Corióideo/complicações , Araquidonato 15-Lipoxigenase/genética , Hibridização Genômica Comparativa , Proteínas de Ligação a DNA , Síndrome de Cornélia de Lange/genética , Síndrome de Cornélia de Lange/cirurgia , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Proteínas Nucleares/genética , Proteínas de Transporte Nucleocitoplasmático/genética , Papiloma do Plexo Corióideo/genética , Papiloma do Plexo Corióideo/cirurgia , Proto-Oncogene Mas , Proteínas de Ligação a RNA , Fatores de TranscriçãoRESUMO
OBJECTS: Epigenetic alterations, known as epimutations, act by deregulating gene expression. These epimutations are reversible through the action of chromatin modifiers such as DNA methylation (DNA-met) and histone deacetylases (HDAC) inhibitors. The present study evaluated the effect of 5-azacitidine (5-aza) and sodium butyrate (NaBu) as inhibitors of DNA-met and HDAC, respectively, in the expression of genes involved in apoptosis. METHODS: D54-MG, U373-MG, and T98G cell lines were exposed to 8 mM of NaBu and 12 µM of 5-aza, as well as a combination of both, for 24 h. The expression of the Bcl-2, Bak-1, Bax, Caspase-3, and Caspase-9 genes was assessed by RT-PCR. RESULTS: They show that the Bcl-2, Caspase-3, and Caspase-9 genes were not expressed by the U373-MG and T98G lines, and that the D54-MG line did not express Bak-1. After treatment, however, these cell lines expressed all of the genes due to the effect of 5-aza on Bak-1 in D54-MG and Caspase-9 in T98G, which suggests repression by DNA-met. Meanwhile, Bcl-2, Caspase-3, and Caspase-9 were in the U373-MG and T98G lines expressed after NaBu treatment. The effect of 5-aza induced an increase in the expression of Bax and Bcl-2, while NaBu produced a similar effect on the Bak-1 and Bax genes. CONCLUSIONS: Results reveal that histone deacetylation is the principle mechanism for repressing these genes and that their basal expression is regulated primarily by this form of histone modification.
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Apoptose/fisiologia , Astrocitoma/genética , Astrocitoma/metabolismo , Epigênese Genética/fisiologia , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , HumanosRESUMO
PURPOSE: Astrocytomas are the most frequent type of tumor of the central nervous system in children. Hence, it is important to describe markers that may improve our understanding of their behavior. Mature microRNAs (miRNAs) may be such biological markers. They are small molecules of RNA that regulate gene expression post-transcriptionally. Due to their importance in cancer, the objective of the present study was to determine the profile of expression of precursor and mature forms of miR-124-3p, miR-128-1, and miR-221-3p using RT-qPCR in pediatric samples. METHODS: A total of 57 astrocytomas embedded in paraffin were selected. As controls, the study included 13 samples of normal brain tissue. RESULTS: Three of eight miRNAs were selected after a preliminary screening. All the miRNAs showed higher levels of expression in normal brain tissue. The expression of miR-124-3p and miR-128-1 decreased in astrocytomas than in normal brain tissue in all grades (p < 0.05 in both cases), and this reduction was most evident in GIV (407- and 1,469-fold, respectively); however, the expression of the precursor forms pre-miR-128-1 and pre-miR-221 was higher in GIV (3.5-fold) than in GI. The levels of miR-128-1 were higher in infratentorial tumors than in supratentorial cases (p = 0.006). Finally, the expression of miR-221-3p was higher in non-recurrent tumors and live patients (p = 0.0185 and p = 0.0004, respectively). CONCLUSIONS: The low expression of these miRNAs may constitute a potential marker of astrocytomas that correlates with localization, possibly due to alterations in the maturation processes of these miRNAs that produced low mature forms in patients with recurrent pediatric astrocytomas.
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Astrocitoma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , MicroRNAs/biossíntese , Astrocitoma/genética , Biomarcadores Tumorais/genética , Criança , Pré-Escolar , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Masculino , México , Gradação de Tumores , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Ferruginous bodies (FBs) are iron-coated entities that form in the body around inorganic fibers or other particulates that can serve as indicators of exposure to inorganic dust. Studies of FB have been conducted consistently in the lungs of adults but have not been explored in children during the past 20 years. The objective of this work was to quantify the FB, classify them as to morphological type and conduct a mineralogical analysis using the energy dispersive X-ray microanalysis (EDXA) with samples obtained from 72 autopsies performed on children. Three grams of lung tissue were digested in commercial bleach, and all the FB found were quantified. The FB from the positive cases was analyzed by EDXA. Results show that 17% of cases presented FB with a median concentration of 5.7 ferruginous bodies per gram of dry weight (FB/g). Larger quantities of FB were recovered from the lungs of rural residents, at concentrations of 11.33 FB/g. Ten cases of children under 5 years of age also presented 5.7 FB/g, but none of these groups showed significant differences when compared to populations of children residing in Mexico City or to children over 5 years of age (p > 0.05). Type-1 FB was the predominant morphological form present. All FB were aluminosilicates. It can be concluded that Mexican children retain FB at low concentrations. All the cores of the FB analyzed in this study were aluminosilicates. Only one contained kaolinite, while the other 10 consisted of some kind of feldspar or clay-like mineral and may thus reflect intramural exposure in children.
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Silicatos de Alumínio/análise , Pulmão/química , Material Particulado/análise , Criança , Pré-Escolar , Elementos Químicos , Exposição Ambiental , Feminino , Humanos , Masculino , MéxicoRESUMO
OBJECTS: The protein 300 (p300) and p300/CBP-binding protein-associated factor (PCAF) are enzymes with histone acetyltransferase (HAT) activity, a function that can become deregulated in different tumors and affect biological responses. METHODS: Due to the lack of information on the deregulation of these HATs in pediatric tumors, this study evaluated the expression of both the mRNA and proteins of p300 and PCAF in 54 samples of pediatric astrocytomas embedded in paraffin. RESULTS: PCAF was not expressed in normal brain tissue. In grade I tumors, the expression of p300 (1.1 ± 0.1) and PCAF (1.2 ± 0.11) was greater than those observed in grade III tumors: 0.72 ± 0.15 for p300 and 0.55 ± 0.11 for PCAF, and grade IV tumors: 0.74 ± 0.13 for p300 and 0.55 ± 0.13 for PCAF (p < 0.05). Immunohistochemical staining revealed the same tendency towards a decrease in the expression of the protein as the degree of clinical severity increased. Patients with recurrent grades I, III, and IV tumors had the highest levels of PCAF, compared to those who showed no recurrence (p < 0.05). CONCLUSIONS: This work describes and confirms that these HATs play important roles in regulating genes and in the biological behavior of pediatric astrocytomas.
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Astrocitoma/genética , Neoplasias Encefálicas/genética , Proteína p300 Associada a E1A/genética , Recidiva Local de Neoplasia/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição de p300-CBP/genética , Astrocitoma/metabolismo , Astrocitoma/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Criança , Proteína p300 Associada a E1A/metabolismo , Humanos , Imuno-Histoquímica , Gradação de Tumores , Recidiva Local de Neoplasia/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição de p300-CBP/metabolismoRESUMO
OBJECTIVE: The objective of this study was to describe the toxicity induced by curcumin in human astrocytoma cell lines. METHODS: The effects induced by curcumin, at 100 µM for 24 h, were evaluated in four astrocytoma cell lines using crystal violet assay and through the evaluation of morphological and ultrastructural changes by electron microscopy. Also, the results of vital staining with acridine orange and propidium iodide for acidic vesicles and apoptotic bodies were analyzed and the expression of the Beclin1 gene was assessed by RT-PCR. RESULTS: The cells treated with curcumin at 100 µM induced an inhibitory concentration50 of viability with morphological changes characterized by a progressive increase in large, non-acidic vesicles devoid of cytoplasmic components and organelles, but that conserved the cell nuclei. No DNA breakage was observed. The astrocytoma cells showed no apoptosis, necrosis or autophagy. Expression of BECLIN1 was not induced (p < 0.05) by curcumin in the astrocytoma cells. CONCLUSIONS: Curcumin at 100 µm induced a new type of death cell in astrocytoma cell lines.
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Antineoplásicos/farmacologia , Astrócitos/efeitos dos fármacos , Curcumina/farmacologia , Antineoplásicos/química , Proteínas Reguladoras de Apoptose/genética , Astrócitos/metabolismo , Astrócitos/ultraestrutura , Astrocitoma/metabolismo , Astrocitoma/patologia , Proteína Beclina-1 , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Humanos , Concentração Inibidora 50 , Proteínas de Membrana/genética , Microscopia Eletrônica de Transmissão , Estrutura MolecularRESUMO
Pregnancy requires a high demand of energy, which leads to an increase of oxidative stress. The aim of this study was to assess the oxidative status in 200 couples of pregnant women-newborns at the time of delivery, for the first time, who gave birth in two University Hospitals from the province of Seville. Recruited women filled an epidemiological questionnaire with their demographic characteristics and dietary habits during pregnancy. At the time of delivery, both maternal and cord blood samples were collected. Protein oxidation, superoxide dismutase, and catalase levels were measured to assess the oxidative status of these women, together with the levels of vitamins D, B12, Zn, Se, and Cu. Our results showed a tendency for all biomarkers measured to be higher in cord blood than in maternal blood. For the correlations established between the OS markers and sociodemographic characteristics, only significant differences for carbonyl groups values were found on both maternal and cord blood, relating these higher values to the use of insecticides in the women's homes. For newborns, only a significant correlation was detected between antioxidant enzymes and the newborn's weight, specifically for superoxide dismutase activity. Additionally, the higher values obtained in cord blood might suggest metabolization, while a higher production of ROS and antioxidant enzymes might be required to maintain the balance. Measured levels for Se were similar in both maternal and cord blood, unlike Cu and Zn, where higher levels were found for maternal blood than cord blood, indicating a correlation between maternal Se values and SOD as OS biomarker. Furthermore, vitamin D levels were around the optimum values established, finding a relationship between vitamin D and new-born's height, unlike for vitamin B12 values, where a correlation with maternal food consumption characteristics was established. Overall values were inside normal ranges and consistent for our population.
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Antioxidantes , Superóxido Dismutase , Recém-Nascido , Gravidez , Humanos , Feminino , Espanha , Estudos Prospectivos , Vitamina D , Relações Mãe-FilhoRESUMO
X-linked myopathy with excessive autophagy is a rare inherited disease characterized by aberrant accumulation of autophagic vacuoles in skeletal muscle. Affected males usually show a slow progression and the heart is characteristically spared. We present four male patients from the same family with an extremely aggressive form of this disease, requiring permanent mechanical ventilation from birth. Ambulation was never achieved. Three died, one in the first hour of life, one at 7 years and one at 17 years, the last death being a consequence of heart failure. Muscle biopsy showed pathognomonic features of the disease in the 4 affected males. Genetic study found a novel synonymous variant in VMA21, c.294C>T (Gly98=). Genotyping was consistent with co-segregation with the phenotype in an X-linked recessive manner. An alteration of the normal splice pattern was confirmed by transcriptome analysis, proving that the apparently synonymous variant was the cause of this extremely severe phenotype.
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Nowadays there is an increasing concern about exposition during prenatal stage to environmental pollutants such as metals, that make pregnant women a vulnerable group of population. Numerous studies have shown associations between the prenatal exposition to some metals and an impact on cognitive, motor and intellectual development of the child. Metals and metalloid are ubiquitous in the environment and pregnant women are exposed to them though their diet, lifestyle factors or occupational and environmental sources. One hundred of maternal and one hundred of cord blood samples were obtained at delivery from pregnant women after signing of the informed consent to determine simultaneously levels of Al, As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Se and Zn by ICP-MS. Among these metals, essential ones (Cu, Mn, Se and Zn) can have health beneficial effects at low levels, however, in high concentration are potentially toxic. On the other hand, elements such as Al, As, Cd, Hg, Pb are classified as toxic metals, no matter what its concentration was. The aim of this study was to find the potential relationships between these metals and metalloid levels, newborn's parameters, pregnancy details and the epidemiologic information obtained using a questionnaire data from the participant pregnant women from Seville (Spain). A n = 100 of participants have been enrolled, 15.6 % of the women from Virgen del Rocio Hospital were smokers during pregnancy but only 11.1 % from Virgen de Valme had the habit. Dietary habits of all participants from both hospital were quite similar in average rice, fish and canned food consumption. The characteristics of newborns were also quite similar for both hospitals. A positive correlation between maternal and cord blood was found between all metals except for Cr and Cu. The strongest correlation was found for Hg (r = 0.779, p < 0.005). Positive but weaker correlations between maternal blood and lifestyle habits were also established.
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Mercúrio , Metaloides , Metais Pesados , Recém-Nascido , Criança , Animais , Feminino , Humanos , Gravidez , Cádmio , Espanha , Sangue Fetal/química , Chumbo , Metais Pesados/análise , Monitoramento AmbientalRESUMO
Affect is involved in many psychological phenomena, but a descriptive structure, long sought, has been elusive. Valence and arousal are fundamental, and a key question-the focus of the present study-is the relationship between them. Valence is sometimes thought to be independent of arousal, but, in some studies (representing too few societies in the world) arousal was found to vary with valence. One common finding is that arousal is lowest at neutral valence and increases with both positive and negative valence: a symmetric V-shaped relationship. In the study reported here of self-reported affect during a remembered moment (N = 8,590), we tested the valence-arousal relationship in 33 societies with 25 different languages. The two most common hypotheses in the literature-independence and a symmetric V-shaped relationship-were not supported. With data of all samples pooled, arousal increased with positive but not negative valence. Valence accounted for between 5% (Finland) and 43% (China Beijing) of the variance in arousal. Although there is evidence for a structural relationship between the two, there is also a large amount of variability in this relation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Emoções , Idioma , Humanos , Autorrelato , Inquéritos e Questionários , Nível de AlertaRESUMO
Ageing is an important determinant of atherosclerosis development rate, mainly by the creation of a chronic low-grade inflammation. Diet, and particularly its fat content, modulates the inflammatory response in the fasting and postprandial states. Our aim was to study the effects of dietary fat on the expression of genes related to inflammation (NF-κB, monocyte chemoattractant protein 1 (MCP-1), TNF-α and IL-6) and plaque stability (matrix metalloproteinase 9, MMP-9) during the postprandial state of twenty healthy, elderly people who followed three diets for 3 weeks each: (1) Mediterranean diet (Med Diet) enriched in MUFA with virgin olive oil; (2) SFA-rich diet; and (3) low-fat, high-carbohydrate diet enriched in n-3 PUFA (CHO-PUFA diet) by a randomised crossover design. At the end of each period, after a 12-h fast, the subjects received a breakfast with a composition similar to the one when the dietary period ended. In the fasting state, the Med Diet consumption induced a lower gene expression of the p65 subunit of NF-κB compared with the SFA-rich diet (P = 0·019). The ingestion of the Med Diet induced a lower gene postprandial expression of p65 (P = 0·033), MCP-1 (P = 0·0229) and MMP-9 (P = 0·041) compared with the SFA-rich diet, and a lower gene postprandial expression of p65 (P = 0·027) and TNF-α (P = 0·047) compared with the CHO-PUFA diet. Direct plasma quantification mostly reproduced the findings. Our data suggest that consumption of a Med Diet reduces the postprandial inflammatory response in mononuclear cells compared with the SFA-rich and CHO-PUFA diets in elderly people. These findings may be partly responsible for the lower CVD risk found in populations with a high adherence to the Med Diet.
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Aterosclerose/metabolismo , Dieta Mediterrânea , Gorduras na Dieta/farmacologia , Regulação da Expressão Gênica/fisiologia , Inflamação/metabolismo , Idoso , Aterosclerose/genética , Estudos Cross-Over , Feminino , Análise de Alimentos , Humanos , Inflamação/genética , Leucócitos Mononucleares/metabolismo , Lipídeos/sangue , Masculino , NF-kappa B/genética , NF-kappa B/metabolismoRESUMO
Inorganic fibers form part of the complex mixture of environmental pollutants in Mexico City and in general locations. Upon entering the lungs, some of those fibers are transformed into ferruginous bodies (FB) that can be used as biological markers of exposure to fibers. Hence, the objectives of this study were, first, to describe the most frequent types of FB found in the lungs, and second, to determine the elemental composition of the cores of some of those FB. A total of 264 lung samples collected from autopsies performed at the National Institutes of Health in Mexico City were analyzed. The FB were obtained by digesting the samples in commercial bleach and all the FB were then collected in 0.45 µm Millipore membranes. All the FB obtained from each case were counted directly under bright field microscopy, and then classified by morphology. Results showed from 14.5 FB/g in Category 1 (housewives), to 50.2 FB/g for samples from Category 5 (construction workers), and 152 FB/g for Category 6 (miners). Significant differences were found upon comparing samples from Categories 5/6 to Category 1 (p < 0.05). Type 1 FB were the most frequent ones seen in the samples from Categories 1 to 5. Elemental analyses of the cores of several FB found aluminosilicates, fiberglass, tremolite and amosite asbestos among others. In conclusion, residents of Mexico show exposures to a variety of fibers that induce FB including asbestos.
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Poluentes Ambientais/análise , Pulmão/química , Adulto , Cloretos/análise , Monitoramento Ambiental , Feminino , Vidro/análise , Humanos , Masculino , México , Silicatos/análise , Adulto JovemRESUMO
OBJECTIVES: In order to evaluate the improvement of the photodynamic therapy (PDT) due to sodium butyrate (NaBu), its effectiveness in U373-MG and D54-MG astrocytoma cell lines was evaluated. METHODS: Cells were exposed to delta-aminolevulinic acid (δ-ALA) as a precursor to endogenous photosensitizer protoporphyrin IX (PpIX). In both astrocytoma cells, an important increase by ALA was observed in uroporphyrinogen synthetase gene expression: 1.8- and 52-fold for D54-MG and U373-MG cells, respectively. After irradiation, they showed 16.67 and 28.9% of mortality in U373-MG and D54-MG, respectively. These mortalities increased to 70.62 and 96.7% when U373-MG and D54-MG cells, respectively, were exposed 24 h to 8 mM NaBu, before to PpIX induction. NaBu induced expression of caspase-3, caspase-9, and Bcl-2 and increased Bax in U373-MG cells. ALA-induced morphological changes are compatible to differentiation. CONCLUSIONS: Genes and differentiation induced mainly by NaBu improve cell death performed by PDT in astrocytoma cells. These facts prove the synergistic effect of NaBu on cytotoxic damage induced by PDT.
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Butiratos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Protoporfirinas/farmacologia , Astrocitoma/metabolismo , Astrocitoma/patologia , Caspases/genética , Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Densitometria , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
In the present research, we examined the links among relative financial scarcity, thinking style, fatalism, and well-being and their roles in predicting protective behaviors against COVID-19. Study 1 (N = 120) revealed that after an experimental manipulation to induce the perception of relative financial scarcity (versus financial abundance), people who perceived higher relative financial scarcity changed their thinking style to a more concrete mindset. In Study 2 (N = 873), the relative financial abundance-scarcity situation was measured, and the results showed that the greater the perceived relative financial scarcity was, the more concrete the mindset and the lower the sense of well-being. Importantly, we found that individuals who felt poorer but maintained an abstract thinking style reported higher well-being. Study 3 (N = 501) examined the influence of a concrete thinking style in people who perceived that their economic situation had worsened with the pandemic. The results showed that when this vulnerable population presented a more concrete mindset, they reported lower well-being, higher fatalism, and lower protective behavior against COVID-19. Thus, maintaining an abstract mindset promotes higher well-being, lower fatalism, and greater protective behaviors against COVID-19, even under economic difficulties. Because thinking style can be modified, our results encourage the development of new social intervention programs to promote an abstract mindset when people face important challenges.
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COVID-19 , Humanos , Pensamento , CogniçãoRESUMO
Many governments invest public funds in communication interventions and campaigns against prostitution and sexual exploitation in an attempt to change attitudes toward prostitution and eventually decrease its consumption. Despite the considerable investment that public institutions have made in campaigns against prostitution and sexual slavery, no known empirical studies have evaluated the effectiveness of such campaigns on attitudes and behavioral change. The messages of these campaigns usually center on one of two thematic focuses: Prostituted women who suffer exploitation and male consumers of prostitution. The present study examines the impact of different anti-prostitution advertisements on attitudes among male participants (N = 155 male participants). Specifically, the experiment aims to test the differential effect of these two focuses, compared to a no-advertisement control condition, on social support for prostitution, negative and incorrect beliefs about prostitutes, and family values related to prostitution. The results show that compared with the no-advertisement control condition, advertisements focused on men who use prostitutes have a significant effect on social support toward prostitution and incorrect beliefs about prostitutes, whereas advertisements focused on female prostitutes have no effect. The results have practical implications for governments and councils regarding the efficacy of this kind of public communication campaign against prostitution consumption.