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1.
Int J Behav Med ; 21(2): 258-65, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23605558

RESUMEN

BACKGROUND: Psychological factors play a crucial role in the well-being of chronically ill patients. PURPOSE: This research examined coping, depressive symptoms and subjective well-being (SWB) in patients with heart failure (HF). The study also analysed whether depressive symptoms mediated the association between coping strategies and SWB. METHOD: Participants (N = 60, 68.3 % men, aged between 40 and 89 years old) diagnosed with HF were recruited from the cardiology service of a general hospital. Coping strategies were assessed with 16 items of the Brief COPE Scale. The items were organised, according to theoretical and empirical data, into four types of coping: task-focused, seeking social support, maladaptive emotion-focused and acceptance coping. Depressive symptoms were assessed with the corresponding subscale of the Hospital Anxiety and Depression Scale. SWB was assessed considering the Satisfaction with Life Scale and the Positive and Negative Affect Schedule. RESULTS: The multiple regression analyses carried out indicated that SWB was positively associated with task-focused coping and inversely related to maladaptive strategies and depressive symptoms. Gender was also a significant predictor of SWB, with male patients reporting higher well-being than female patients. The mediational analysis showed that depressive symptoms partially mediated the relationships between task-focused coping and SWB. CONCLUSION: Results were discussed in the light of the importance of gender, depression and coping in patients with HF since these factors may affect subjective well-being and contribute to severe physical impairment.


Asunto(s)
Adaptación Psicológica , Depresión/psicología , Estado de Salud , Insuficiencia Cardíaca/psicología , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/psicología , Enfermedad Crónica , Emociones , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Factores Sexuales , Apoyo Social , Encuestas y Cuestionarios
2.
Heliyon ; 10(9): e30650, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38756612

RESUMEN

The European Union supports the use of technology to improve public procurement, acknowledging Building Information Modeling (BIM) as a catalyst for cost-effective public works and innovation. The purpose of this paper is to evaluate BIM implementation practices in Spanish public procurement. The methodology used in this study is a mixed research method involving a questionnaire survey and semi-structured expert interviews. The findings reveal market maturity as a barrier to BIM adoption in Spanish public procurement throughout the asset lifecycle. Selecting the right instrument for implementation proves challenging for public organizations. This study has contributed to the development of more practical and effective strategies to ensure full adoption of BIM within the public procurement sector of Spain. It proposes a framework approach for the pre-contractual phase, helping contracting authorities to make the optimal instrument selection. Two criteria are considered: the maturity of the public client and sector, and the economic value classification of tenders.

3.
Biochim Biophys Acta Gene Regul Mech ; 1866(2): 194938, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37086967

RESUMEN

Dysregulation of cholesterol homeostasis is associated with several pathologies including cardiovascular diseases and neurological disorders such as Alzheimer's disease (AD). MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of cholesterol metabolism. We previously established the role of miR-7 in regulating insulin resistance and amyloidosis, which represents a common pathological feature between type 2 diabetes and AD. We show here an additional metabolic function of miR-7 in cholesterol biosynthesis. We found that miR-7 blocks the last steps of the cholesterol biosynthetic pathway in vitro by targeting relevant genes including DHCR24 and SC5D posttranscriptionally. Intracranial infusion of miR-7 on an adeno-associated viral vector reduced the expression of DHCR24 in the brain of wild-type mice, supporting in vivo miR-7 targeting. We also found that cholesterol regulates endogenous levels of miR-7 in vitro, correlating with transcriptional regulation through SREBP2 binding to its promoter region. In parallel to SREBP2 inhibition, the levels of miR-7 and hnRNPK (the host gene of miR-7) were concomitantly reduced in brain in a mouse model of Niemann Pick type C1 disease and in murine fatty liver, which are both characterized by intracellular cholesterol accumulation. Taken together, the results establish a novel regulatory feedback loop by which miR-7 modulates cholesterol homeostasis at the posttranscriptional level, an effect that could be exploited for therapeutic interventions against prevalent human diseases.


Asunto(s)
Diabetes Mellitus Tipo 2 , MicroARNs , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Humanos , Ratones , Animales , MicroARNs/genética , MicroARNs/metabolismo , Regulación de la Expresión Génica , Colesterol/metabolismo , Homeostasis , Proteínas del Tejido Nervioso/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/metabolismo
4.
Adicciones ; 24(1): 59-67, 2012.
Artículo en Español | MEDLINE | ID: mdl-22508018

RESUMEN

The emotions predispose to action providing information from both internal and external environment. There is evidence indicating that the emotional response in drugdependent patients is different from that of the not consuming population. The present work analyzed the emotions of drugdependent under ambulatory treatment (N=57), following the Lang's theory of emotion, considering the dimensions of valence, arousal and dominance or control, across the International Affective Picture System (IAPS), individually applied. The results were contrasted with a control group of not consuming persons (N=44) of similar age, since this variable concerns emotional experience. The influence of sex was also analyzed, considering the possible differences between men and women in emotional experience. The results can be summarized in the following points: (1) There were significant differences between substance abusers and not consumers in the dimension of valence, valuing the consumers the emotional stimuli of the most extreme form (the agreeable ones as better, and the disagreeable ones as worse); (2) there were no differences between both groups in the arousal and dominance dimensions; and (3) women reported more arousal before aversive images, and less before the sexual ones, than males, independently of they were or not substance abusers. Finally, it is suggested the need to deep into the analysis of sex differences and into the images selected, as well as into the usefulness of the emotion centred therapies for the treatment of drugdependency.


Asunto(s)
Emociones , Trastornos Relacionados con Sustancias/psicología , Adolescente , Adulto , Anciano , Atención Ambulatoria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/terapia , Adulto Joven
5.
Front Psychol ; 13: 883833, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35712170

RESUMEN

Borderline personality disorder (BPD) is characterized by instability in relationships, mood fluctuations, and erratic behavior. This study investigates the relationship between pathological personality traits and functional disability, the status of perceived social support in BPD, as well as its mediating role in this relationship. In this cross-sectional study, 192 Spanish women (BPD group, N = 97; healthy control group, N = 95) completed, through two online platforms, a battery of tests including: the Personality Inventory for DSM-5 Brief Form (PID-5-BF), the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) and the Perceived Social Support subscale of the Quality of Life Questionnaire (QLQ). The results show that perceived social support was significantly lower in the BPD group, which also presented a significantly higher disability score than the control group. Pathological personality traits affected functionality both directly and indirectly through perceived social support, as this variable was a significant mediator in both groups. We conclude that perceived social support is impaired in BPD patients, and enhancing it as a complementary therapy to evidence-based treatments could help preserve the functionality of patients while pathological traits are regulated. This study also encourages future research to delve into the relevance of other psychosocial variables on the functionality of subjects with BPD, and the need of enhancing them in therapy.

6.
Biomolecules ; 12(2)2022 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-35204710

RESUMEN

Insulin resistance defines an impairment in the biologic response to insulin action in target tissues, primarily the liver, muscle, adipose tissue, and brain. Insulin resistance affects physiology in many ways, causing hyperglycemia, hypertension, dyslipidemia, visceral adiposity, hyperinsulinemia, elevated inflammatory markers, and endothelial dysfunction, and its persistence leads to the development metabolic disease, including diabetes, obesity, cardiovascular disease, or nonalcoholic fatty liver disease (NAFLD), as well as neurological disorders such as Alzheimer's disease. In addition to classical transcriptional factors, posttranscriptional control of gene expression exerted by microRNAs and RNA-binding proteins constitutes a new level of regulation with important implications in metabolic homeostasis. In this review, we describe miRNAs and RBPs that control key genes involved in the insulin signaling pathway and related regulatory networks, and their impact on human metabolic diseases at the molecular level, as well as their potential use for diagnosis and future therapeutics.


Asunto(s)
Resistencia a la Insulina , Enfermedades Metabólicas , Enfermedad del Hígado Graso no Alcohólico , Regulación de la Expresión Génica , Humanos , Insulina/metabolismo , Resistencia a la Insulina/genética , Enfermedades Metabólicas/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo
7.
Front Cardiovasc Med ; 9: 994080, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36407436

RESUMEN

Hypoxia is a crucial factor contributing to maintenance of atherosclerotic lesions. The ability of ABCA1 to stimulate the efflux of cholesterol from cells in the periphery, particularly foam cells in atherosclerotic plaques, is an important anti-atherosclerotic mechanism. The posttranscriptional regulation by miRNAs represents a key regulatory mechanism of a number of signaling pathways involved in atherosclerosis. Previously, miR-199a-5p has been shown to be implicated in the endocytic and retrograde intracellular transport. Although the regulation of miR-199a-5p and ABCA1 by hypoxia has been already reported independently, the role of miR-199a-5p in macrophages and its possible role in atherogenic processes such us regulation of lipid homeostasis through ABCA1 has not been yet investigated. Here, we demonstrate that both ABCA1 and miR-199a-5p show an inverse regulation by hypoxia and Ac-LDL in primary macrophages. Moreover, we demonstrated that miR-199a-5p regulates ABCA1 mRNA and protein levels by directly binding to its 3'UTR. As a result, manipulation of cellular miR-199a-5p levels alters ABCA1 expression and cholesterol efflux in primary mouse macrophages. Taken together, these results indicate that the correlation between ABCA1-miR-199a-5p could be exploited to control macrophage cholesterol efflux during the onset of atherosclerosis, where cholesterol alterations and hypoxia play a pathogenic role.

8.
Front Cardiovasc Med ; 9: 908070, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35711383

RESUMEN

Monocytes participate in the development of atherosclerosis through the action of cytokines and other inflammatory mediators. Among them, CCR2 and its ligands, CCL2 and CCL7 play an important role, so the main objective of this work was to determine whether genetic variants affecting their activity were associated with cardiovascular disease. A cohort of 519 patients that have suffered coronary events was analyzed under a propensity score-matching protocol selecting a homogeneous set of cases and controls, according to age, sex, smoking status, dyslipidemia, arterial hypertension and type 2 diabetes as risk factors. While dyslipidemia and arterial hypertension were more prevalent among patients with angina pectoris, current smoking status and elevated inflammatory markers, including total leukocyte and monocyte counts, were more likely associated with acute coronary events. Propensity score matching analysis, performed to eliminate the influence of these risk factors and highlight genetic modifiers, revealed that a single nucleotide variant, rs17735770 at the 3'untranslated region of the CCL7 gene transcript, was associated with decreased cardiovascular risk in a group represented mostly by men, with an average age of 57, and without significant differences in traditional risk factors. Furthermore, the presence of this variant altered the local mRNA structure encompassing a binding site for miR-23ab, resulting in increased translation of a reporter gene in a miR23 independent fashion. The rs17735770 genetic variant led to increased expression of CCL7, a potential antagonist of CCR2 at inflammatory sites, where it could play a meaningful role during the evolution of atherosclerosis.

9.
Cells ; 11(16)2022 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-36010613

RESUMEN

The evident implication of the insulin-degrading enzyme (IDE) in Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM), among its capacity to degrade insulin and amyloid-ß peptide (Aß), suggests that IDE could be an essential link in the relation between hyperinsulinemia, insulin resistance and AD. However, little is known about the cellular and molecular regulation of IDE expression, and even less has been explored regarding the post-transcriptional regulation of IDE, although it represents a great molecular target of interest for therapeutic treatments. We recently described that miR-7, a novel candidate for linking AD and T2DM at the molecular level, regulates IDE and other key genes in both pathologies, including some key genes involved in the insulin signaling pathway. Here, we explored whether other miRNAs as well as other post-transcriptional regulators, such as RNA binding proteins (RBP), could potentially participate in the regulation of IDE expression in vitro. Our data showed that in addition to miR-7, miR-125, miR-490 and miR-199 regulate IDE expression at the post-transcriptional level. Moreover, we also found that IDE contains multiple potential binding sites for several RBPs, and a narrow-down prediction analysis led us to speculate on a novel regulation of IDE by RALY and HuD. Taken together, these results demonstrate the novel players controlling IDE expression that could represent potential therapeutical targets to treat several metabolic diseases with a high impact on human health, including AD and T2DM.


Asunto(s)
Enfermedad de Alzheimer , Diabetes Mellitus Tipo 2 , Insulisina , MicroARNs , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo C , Humanos , Insulina/metabolismo , Insulisina/metabolismo , MicroARNs/genética , MicroARNs/uso terapéutico
10.
Span J Psychol ; 14(1): 356-65, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21568192

RESUMEN

Fifty-two men who had suffered a first episode ischemic heart disease reported their degree of life satisfaction, the strategies they used to adjust to the illness, and the symptoms of anxiety and depression they felt. The multiple regression analyses carried out indicated that emotional distress was associated with a lower level of life satisfaction. In the analyses of anxiety symptoms, the use of negative adjustment strategies was also a significant predictor. Lastly, a significant Life Satisfaction x Type of Adjustment interaction was obtained. According to this, the patients who felt more satisfaction with their lives used more positive strategies to adjust to the illness and fewer negative ones, than the group of patients who were less satisfied. In conclusion, life satisfaction predicts emotional wellbeing of patients with ischemic heart disease and it enhances the implementation of appropriate strategies to cope with the disease. Moreover, although life satisfaction has been considered a stable measure, we suggest it may change as the experience of illness limits individuals' important goals.


Asunto(s)
Adaptación Psicológica , Angina de Pecho/psicología , Ansiedad/psicología , Depresión/psicología , Infarto del Miocardio/psicología , Isquemia Miocárdica/psicología , Calidad de Vida/psicología , Rol del Enfermo , Adulto , Anciano , Angina de Pecho/diagnóstico , Ansiedad/diagnóstico , Mecanismos de Defensa , Depresión/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Inventario de Personalidad/estadística & datos numéricos , Psicometría , Apoyo Social
11.
Antioxidants (Basel) ; 10(12)2021 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-34943132

RESUMEN

The liver's high metabolic activity and detoxification functions generate reactive oxygen species, mainly through oxidative phosphorylation in the mitochondria of hepatocytes. In contrast, it also has a potent antioxidant mechanism for counterbalancing the oxidant's effect and relieving oxidative stress. PAS kinase (PASK) is a serine/threonine kinase containing an N-terminal Per-Arnt-Sim (PAS) domain, able to detect redox state. During fasting/feeding changes, PASK regulates the expression and activation of critical liver proteins involved in carbohydrate and lipid metabolism and mitochondrial biogenesis. Interestingly, the functional inactivation of PASK prevents the development of a high-fat diet (HFD)-induced obesity and diabetes. In addition, PASK deficiency alters the activity of other nutrient sensors, such as the AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR). In addition to the expression and subcellular localization of nicotinamide-dependent histone deacetylases (SIRTs). This review focuses on the relationship between oxidative stress, PASK, and other nutrient sensors, updating the limited knowledge on the role of PASK in the antioxidant response. We also comment on glucagon-like peptide 1 (GLP-1) and its collaboration with PASK in preventing the damage associated with hepatic oxidative stress. The current knowledge would suggest that PASK inhibition and/or exendin-4 treatment, especially under fasting conditions, could ameliorate disorders associated with excess oxidative stress.

12.
Nutrients ; 13(8)2021 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-34444712

RESUMEN

Glucagon-like peptide 1 (GLP-1) and PAS kinase (PASK) control glucose and energy homeostasis according to nutritional status. Thus, both glucose availability and GLP-1 lead to hepatic glycogen synthesis or degradation. We used a murine model to discover whether PASK mediates the effect of exendin-4 (GLP-1 analogue) in the adaptation of hepatic glycogen metabolism to nutritional status. The results indicate that both exendin-4 and fasting block the Pask expression, and PASK deficiency disrupts the physiological levels of blood GLP1 and the expression of hepatic GLP1 receptors after fasting. Under a non-fasted state, exendin-4 treatment blocks AKT activation, whereby Glucokinase and Sterol Regulatory Element-Binding Protein-1c (Srebp1c) expressions were inhibited. Furthermore, the expression of certain lipogenic genes was impaired, while increasing Glucose Transporter 2 (GLUT2) and Glycogen Synthase (GYS). Moreover, exendin-4 treatment under fasted conditions avoided Glucose 6-Phosphatase (G6pase) expression, while maintaining high GYS and its activation state. These results lead to an abnormal glycogen accumulation in the liver under fasting, both in PASK-deficient mice and in exendin-4 treated wild-type mice. In short, exendin-4 and PASK both regulate glucose transport and glycogen storage, and some of the exendin-4 effects could therefore be due to the blocking of the Pask expression.


Asunto(s)
Adaptación Fisiológica , Ayuno , Glucógeno Hepático/metabolismo , Hígado/metabolismo , Estado Nutricional , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Exenatida/metabolismo , Exenatida/farmacología , Péptido 1 Similar al Glucagón/sangre , Receptor del Péptido 1 Similar al Glucagón/genética , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Glucoquinasa/metabolismo , Glucosa/metabolismo , Transportador de Glucosa de Tipo 2/genética , Transportador de Glucosa de Tipo 2/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Serina-Treonina Quinasas/deficiencia , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Regulación hacia Arriba , Pérdida de Peso
13.
Front Endocrinol (Lausanne) ; 12: 635923, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34122329

RESUMEN

Macrophages are immune cells that play crucial roles in host defense against pathogens by triggering their exceptional phagocytic and inflammatory functions. Macrophages that reside in healthy tissues also accomplish important tasks to preserve organ homeostasis, including lipid uptake/efflux or apoptotic-cell clearance. Both homeostatic and inflammatory functions of macrophages require the precise stability of lipid-rich microdomains located at the cell membrane for the initiation of downstream signaling cascades. Caveolin-1 (Cav-1) is the main protein responsible for the biogenesis of caveolae and plays an important role in vascular inflammation and atherosclerosis. The Liver X receptors (LXRs) are key transcription factors for cholesterol efflux and inflammatory gene responses in macrophages. Although the role of Cav-1 in cellular cholesterol homeostasis and vascular inflammation has been reported, the connection between LXR transcriptional activity and Cav-1 expression and function in macrophages has not been investigated. Here, using gain and loss of function approaches, we demonstrate that LXR-dependent transcriptional pathways modulate Cav-1 expression and compartmentation within the membrane during macrophage activation. As a result, Cav-1 participates in LXR-dependent cholesterol efflux and the control of inflammatory responses. Together, our data show modulation of the LXR-Cav-1 axis could be exploited to control exacerbated inflammation and cholesterol overload in the macrophage during the pathogenesis of lipid and immune disorders, such as atherosclerosis.


Asunto(s)
Caveolina 1/biosíntesis , Colesterol/metabolismo , Receptores X del Hígado/biosíntesis , Macrófagos/metabolismo , Transportador 1 de Casete de Unión a ATP/metabolismo , Animales , Antiinflamatorios , Apolipoproteína A-I/metabolismo , Aterosclerosis/metabolismo , Caveolina 1/genética , Membrana Celular/metabolismo , Detergentes , Expresión Génica , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Inflamación , Ratones , Ratones Endogámicos C57BL , Células RAW 264.7 , Transducción de Señal , Transcripción Genética
14.
Front Endocrinol (Lausanne) ; 11: 594053, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33391184

RESUMEN

The protein kinase with PAS domains (PASK) is a nutrient and energy sensor located in the cells of multiple organs. Many of the recent findings for understanding PASK functions in mammals have been reported in studies involving PASK-deficient mice. This minireview summarizes the PASK role in the control of fasting and feeding responses, focusing especially on the hypothalamus and liver. In 2013, PASK was identified in the hypothalamic areas involved in feeding behavior, and its expression was regulated under fasting/refeeding conditions. Furthermore, it plays a role in coordinating the activation/inactivation of the hypothalamic energy sensors AMPK and mTOR/S6K1 pathways in response to fasting. On the other hand, PASK deficiency prevents the development of obesity and non-alcoholic fatty liver in mice fed with a high-fat diet. This protection is explained by the re-establishment of several high-fat diet metabolic alterations produced in the expression of hepatic transcription factors and key enzymes that control the main metabolic pathways involved in maintaining metabolic homeostasis in fasting/feeding responses. This minireview covers the effects of PASK inactivation in the expression of certain transcription factors and target enzymes in several metabolic pathways under situations such as fasting and feeding with either a standard or a high-fat diet.


Asunto(s)
Metabolismo Energético , Ayuno , Homeostasis , Nutrientes/análisis , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Métodos de Alimentación , Humanos , Proteínas Serina-Treonina Quinasas/genética
15.
Aging (Albany NY) ; 12(3): 2275-2301, 2020 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-31974316

RESUMEN

Several signaling pathways may be affected during aging. All are regulated by nutrient levels leading to a decline in mitochondrial function and autophagy and to an increase in oxidative stress. PAS Domain Kinase (PASK) is a nutrient and bioenergetic sensor. We have previously found that PASK plays a role in the control of hepatic metabolic balance and mitochondrial homeostasis. To investigate PASK's role in hepatic oxidative stress during aging, we analyzed the mitochondrial function, glucose tolerance, insulin resistance, and lipid-related parameters in aged PASK-deficient mice. Hepatic Pask mRNA decreased in step with aging, being undetectable in aged wild-type (WT) mice. Aged PASK-deficient mice recorded lower levels of ROS/RNS compared to aged WT. The regulators of mitochondrial biogenesis, PGC1a, SIRT1 and NRF2, decreased in aged WT, while aged PASK-deficient mice recorded a higher expression of NRF2, GCLm and HO1 proteins and CS activity under fasted conditions. Additionally, aged PASK-deficient mice recorded an overexpression of the longevity gene FoxO3a, and maintained elevated PCNA protein, suggesting that hepatic cell repair mechanisms might be functional. PASK-deficient mice have better insulin sensitivity and no glucose intolerance, as confirmed by a normal HOMA-IR index. PASK may be a good target for reducing damage during aging.


Asunto(s)
Envejecimiento/genética , Proteínas Serina-Treonina Quinasas/genética , Envejecimiento/metabolismo , Animales , Proteína Forkhead Box O3/genética , Regulación del Desarrollo de la Expresión Génica , Intolerancia a la Glucosa/genética , Glutamato-Cisteína Ligasa/metabolismo , Hemo-Oxigenasa 1/metabolismo , Resistencia a la Insulina/genética , Hígado/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Ratones Noqueados , Factor 2 Relacionado con NF-E2/metabolismo , Biogénesis de Organelos , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/metabolismo
16.
Mol Cell Biol ; 39(22)2019 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-31501273

RESUMEN

Brain insulin resistance is a key pathological feature contributing to obesity, diabetes, and neurodegenerative disorders, including Alzheimer's disease (AD). Besides the classic transcriptional mechanism mediated by hormones, posttranscriptional regulation has recently been shown to regulate a number of signaling pathways that could lead to metabolic diseases. Here, we show that microRNA 7 (miR-7), an abundant microRNA in the brain, targets insulin receptor (INSR), insulin receptor substrate 2 (IRS-2), and insulin-degrading enzyme (IDE), key regulators of insulin homeostatic functions in the central nervous system (CNS) and the pathology of AD. In this study, we found that insulin and liver X receptor (LXR) activators promote the expression of the intronic miR-7-1 in vitro and in vivo, along with its host heterogeneous nuclear ribonucleoprotein K (HNRNPK) gene, encoding an RNA binding protein (RBP) that is involved in insulin action at the posttranscriptional level. Our data show that miR-7 expression is altered in the brains of diet-induced obese mice. Moreover, we found that the levels of miR-7 are also elevated in brains of AD patients; this inversely correlates with the expression of its target genes IRS-2 and IDE. Furthermore, overexpression of miR-7 increased the levels of extracellular Aß in neuronal cells and impaired the clearance of extracellular Aß by microglial cells. Taken together, these results represent a novel branch of insulin action through the HNRNPK-miR-7 axis and highlight the possible implication of these posttranscriptional regulators in a range of diseases underlying metabolic dysregulation in the brain, from diabetes to Alzheimer's disease.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Insulina/metabolismo , Receptores X del Hígado/metabolismo , MicroARNs/metabolismo , Receptor de Insulina/metabolismo , Animales , Encéfalo/metabolismo , Línea Celular Tumoral , Ribonucleoproteína Heterogénea-Nuclear Grupo K/metabolismo , Humanos , Insulina/genética , Resistencia a la Insulina , Insulisina/metabolismo , Receptores X del Hígado/genética , Ratones , MicroARNs/genética , Neuronas/metabolismo , Procesamiento Postranscripcional del ARN , Receptor de Insulina/genética , Transducción de Señal
17.
J Nutr Biochem ; 57: 14-25, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29649689

RESUMEN

The prevalence of overweight and obesity in the population, along with their associated complications, is a major factor contributing to increased morbidity and mortality in developed countries. The liver is a vital organ for maintaining metabolic homeostasis, especially in the adjustment periods in fasting and feeding. Per-Arnt-Sim (PAS) kinase (PASK) controls glucose homeostasis and energy metabolism in response to nutritional status. PASK-deficient mice with a high-fat diet (HFD) resist the development of obesity and hepatic steatosis, with improved insulin sensitivity. We have investigated the regulation of the PASK expression in an HFD, as well as its role in adapting to fasting and feeding conditions. PASK-deficient mice with an HFD record improved parameters for the following: body weight, glucose tolerance, insulin resistance and serum lipid parameters. An HFD alters the down-regulation of Pask expression produced by fasting, as normally happens in a standard-fat diet. PASK deficiency blocks or diminishes the expression of many genes overexpressed in HFD-fed mice, such as the following: transcription factors involved in the regulation of gluconeogenic enzymes, the transport of fatty acid into mitochondria, beta-oxidation and de novo lipogenesis. PASK also regulates gene expression posttranscriptionally through the short noncoding RNAs involved in lipid metabolism and glucose homeostasis. The expression of miR-33a and miR-143 changes in PASK-deficient mice with an HFD. Thus, PASK-deficient mice improved their adaptation to feeding/fasting through a highly regulated molecular mechanism that controls the expression and function of the transcription factors, enzymes and miRNAs involved in glucose and insulin signaling.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Ayuno/fisiología , Hígado/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Animales , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Ácidos Grasos/metabolismo , Quinasas del Centro Germinal , Glucoquinasa/metabolismo , Gluconeogénesis/fisiología , Resistencia a la Insulina , Péptidos y Proteínas de Señalización Intracelular , Metabolismo de los Lípidos , Masculino , Ratones Endogámicos C57BL , Ratones Mutantes , MicroARNs , Obesidad/etiología , Obesidad/genética , Proteínas Serina-Treonina Quinasas/genética , Triglicéridos/metabolismo
18.
Rev. psicol. clín. niños adolesc ; 10(1): 53-67, Enero 2023. graf, tab
Artículo en Español | IBECS (España) | ID: ibc-214144

RESUMEN

Los comportamientos autolesivos y suicidas en adolescentes, por su creciente prevalencia como por sus fatales consecuencias, son en nuestrosdías un problema de salud pública que requiere de intervenciones eficaces. Con el objetivo de dilucidar los tratamientos psicológicos que, hasta lafecha, mejor funcionan para reducir o eliminar estos comportamientos, se realizó una revisión de estudios de metaanálisis y revisiones sistemáticasen las bases de datos PsycArticles, PsycInfo y MEDLINE. Los criterios de elegibilidad establecidos permitieron la selección final de 10 registros.Los resultados mostraron una elevada heterogeneidad y un alcance limitado de los tratamientos psicológicos con tamaños del efecto de pequeñosa moderados tanto para las conductas autolesivas, como para la ideación suicida, la suicidabilidad y especialmente para la intención suicida. Estosefectos tendían a debilitarse o desaparecer en el medio y largo plazo. La Terapia Dialéctica Conductual (TDC) resultó ser comparativamente la quemejores resultados obtuvo de las intervenciones analizadas. El alcance restringido de los resultados y las importantes limitaciones metodológicashalladas alertan de la necesidad de más investigación, así como del futuro diseño de intervenciones específicas para este tipo de problemas. (AU)


Self-injurious and suicidal behaviors in adolescents are nowadays a public health problem that requires effective interventions. In order to elucidate the psychological treatments that, to date,work best to reduce or eliminate these behaviors, a review of meta-analysis and systematic reviews was carried out in the PsycArticles, PsycInfo andMEDLINE databases. The established eligibility criteria allowed the final selection of 10 records. The results showed high heterogeneity and poorresults for the psychological treatments with small to moderate effect sizes for self-injurious behaviors, suicidal ideation, suicidality and especiallyfor suicidal attempts. These effects tended to weaken or disappear in the medium to long term. Dialectical Behavior Therapy (DBT) proved to becomparatively the best performing of the interventions analyzed. The limited scope of the results and the important methodological limitations alertus to the need for further research and the future design of specific interventions for this type of problems. (AU)


Asunto(s)
Humanos , Adolescente , Psicoterapia/métodos , Psicoterapia/tendencias , Conducta Autodestructiva/psicología , Conducta Autodestructiva/terapia , Suicidio/psicología , Adolescente , Literatura de Revisión como Asunto , Resultado del Tratamiento
19.
An. psicol ; 38(2): 327-335, may. 2022. tab
Artículo en Español | IBECS (España) | ID: ibc-202893

RESUMEN

Las personas con dependencia emocional presentan preocupaciones constantes sobre el posible abandono o traición por parte de la pareja. De esta forma, ponen en marcha un gran abanico de estrategias retentivas dirigidas a cubrir la gran necesidad de controlar la relación. Además, sienten insatisfacción y frustración en la relación ya que sienten que nunca conseguirán lo que quieren o esperan de ella. Por esto, los objetivos del estudio se dirigen a analizar la posible relación entre la dependencia emocional, la intolerancia a la incertidumbre, la tendencia a las preocupaciones y el pesimismo. Asimismo, se comprueba el papel mediador de estos factores en la relación entre la dependencia emocional y la permanencia en relaciones de pareja violentas debido a la elevada prevalencia de darse conjuntamente en una misma relación. Participaron 258 personas, 77.1% mujeres y 22.9% hombres con edades que oscilaron entre los 18 y 67 años (M = 32.63; DT = 11.66). Los resultados reflejaron relaciones positivas entre la dependencia emocional, la intolerancia a la incertidumbre, la tendencia a las preocupaciones y el pesimismo. Igualmente, se comprueba que la dependencia emocional conduce a la permanencia en relaciones violentas a través de los factores mencionados.(AU)


People with emotional dependence present constant concerns about possible abandonment or betrayal by their partner. In this way, they implement a wide range of retention strategies aimed at covering the great need for control in the relationship. In addition, they feel dissatisfaction and frustration in the relationship since they feel they will never get what they want or expect from it. Therefore, the objectives of the study are aimed at analyzing the possible relationship between emotional dependence, intolerance to uncertainty, tendency to worry and pessimism. Also, the mediating role of these factors in the relationship between emotional dependence and permanence in violent relationships is verified due to the high prevalence of occurring jointly in the same relationship. A total of 258 people participated, 77.1% women and 22.9% men with ages ranging from 18 to 67 (M= 32.63; SD= 11.66). The results reflected positive relationships between emotional dependence, intolerance to uncertainty, tendency to worry andpessimism. Likewise, it is proven that emotional dependence leads to permanence in violent relationships through the factors mentioned.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Ciencias de la Salud , Violencia , Violencia de Género/psicología , Dependencia Psicológica , Incertidumbre , Pesimismo , Relaciones Interpersonales , Codependencia Psicológica
20.
Psicol. conduct ; 30(1): 51-68, abr. 2022. tab, ilus
Artículo en Español | IBECS (España) | ID: ibc-204151

RESUMEN

Los objetivos del estudio fueron evaluar la relación entre la dependencia emocional y la ansiedad social, el miedo a la evaluación negativa y el perfeccionismo disfuncional, así como su papel mediador en la relación entre las influencias paternas perfeccionistas y la violencia física recibida por parte de la pareja. Participaron 258 personas (77,1% mujeres) de entre 18 y 67 años (M= 32,63; DT= 11,66). Los hallazgos sugirieron que la dependencia emocional estaba positivamente asociada a la violencia de pareja recibida, ansiedad social, miedo a la evaluación negativa y perfeccionismo disfuncional. A su vez, la violencia de pareja recibida estaba positivamente asociada al perfeccionismo disfuncional. La dependencia emocional explicó el 16,55% de la relación entre las influencias paternas perfeccionistas, referidas a la percepción de las figuras parentales abiertamente críticas y con expectativas elevadas y la permanencia en relaciones de pareja violentas físicamente. En conclusión, se menciona la necesidad de investigar e incluir estos factores en las intervenciones psicológicas dirigidas a tratar ambas problemáticas como son la dependencia emocional y la permanencia en relaciones violentas.


The objectives of the study were to evaluate the relationship between emotional dependence and social anxiety, fear of negative evaluation and dysfunctional perfectionism, as well as its mediating role in the relationship between perfectionistic parental influences and physical violence received from the partner. A total of 258 people (77.1% female) aged 18-67 years (M= 32.63, SD= 11.66) participated. The findings suggested that emotional dependence was positively associated with intimate partner violence received, social anxiety, fear of negative evaluation, and dysfunctional perfectionism. In turn, intimate partner violence received was positively associated with dysfunctional perfectionism. Emotional dependence explained 16.55% of the relationship between perfectionist parental influences, referring to the perception of openly critical parental figures with high expectations, and the permanence in physically violent intimate partner relationships. In conclusion, the need to investigate and include these factors in psychological interventions aimed at treating both problems such as emotional dependence and permanence in violent relationships is mentioned.


Asunto(s)
Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Violencia de Pareja , Ansiedad , Perfeccionismo , Violencia , Apego a Objetos
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