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1.
Nature ; 619(7970): 491-494, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37316661

RESUMEN

The abundance of refractory elements in giant planets can provide key insights into their formation histories1. Owing to the low temperatures of the Solar System giants, refractory elements condense below the cloud deck, limiting sensing capabilities to only highly volatile elements2. Recently, ultra-hot giant exoplanets have allowed for some refractory elements to be measured, showing abundances broadly consistent with the solar nebula with titanium probably condensed out of the photosphere3,4. Here we report precise abundance constraints of 14 major refractory elements on the ultra-hot giant planet WASP-76b that show distinct deviations from proto-solar and a sharp onset in condensation temperature. In particular, we find nickel to be enriched, a possible sign of the accretion of the core of a differentiated object during the evolution of the planet. Elements with condensation temperatures below 1,550 K otherwise closely match those of the Sun5 before sharply transitioning to being strongly depleted above 1,550 K, which is well explained by nightside cold-trapping. We further unambiguously detect vanadium oxide on WASP-76b, a molecule long suggested to drive atmospheric thermal inversions6, and also observe a global east-west asymmetry7 in its absorption signals. Overall, our findings indicate that giant planets have a mostly stellar-like refractory elemental content and suggest that temperature sequences of hot Jupiter spectra can show abrupt transitions wherein a mineral species is either present or completely absent if a cold trap exists below its condensation temperature8.

2.
Int J Mol Sci ; 25(8)2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38673780

RESUMEN

Cognitive impairment (CI) is a complication of chronic kidney disease (CKD) that is frequently observed among patients. The aim of this study was to evaluate the potential crosstalk between changes in cognitive function and the levels of Klotho in the brain cortex in an experimental model of CKD. To induce renal damage, Wistar rats received a diet containing 0.25% adenine for six weeks, while the control group was fed a standard diet. The animals underwent different tests for the assessment of cognitive function. At sacrifice, changes in the parameters of mineral metabolism and the expression of Klotho in the kidney and frontal cortex were evaluated. The animals with CKD exhibited impaired behavior in the cognitive tests in comparison with the rats with normal renal function. At sacrifice, CKD-associated mineral disorder was confirmed by the presence of the expected disturbances in the plasma phosphorus, PTH, and both intact and c-terminal FGF23, along with a reduced abundance of renal Klotho. Interestingly, a marked and significant decrease in Klotho was observed in the cerebral cortex of the animals with renal dysfunction. In sum, the loss in cerebral Klotho observed in experimental CKD may contribute to the cognitive dysfunction frequently observed among patients. Although further studies are required, Klotho might have a relevant role in the development of CKD-associated CI and represent a potential target in the management of this complication.


Asunto(s)
Corteza Cerebral , Disfunción Cognitiva , Glucuronidasa , Proteínas Klotho , Insuficiencia Renal Crónica , Animales , Masculino , Ratas , Corteza Cerebral/metabolismo , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/etiología , Modelos Animales de Enfermedad , Factor-23 de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Glucuronidasa/metabolismo , Riñón/metabolismo , Proteínas Klotho/metabolismo , Ratas Wistar , Insuficiencia Renal Crónica/metabolismo
3.
Int J Mol Sci ; 24(16)2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37629118

RESUMEN

Atherosclerosis is initiated by the activation of endothelial cells that allows monocyte adhesion and transmigration through the vascular wall. The accumulation of uremic toxins such as indoxyl sulphate (IS) and p-cresol (PC) has been associated with atherosclerosis. Currently, miRNAs play a crucial role in the regulation of monocyte activation, adhesion, and trans-endothelial migration. The aim of the present study is to evaluate the effect of IS and PC on monocyte adhesion and migration processes in monocytes co-cultured with endothelial cells as well as to determine the underlying mechanisms. The incubation of HUVECs and THP-1 cells with both IS and PC toxins resulted in an increased migratory capacity of THP-1 cells. Furthermore, the exposure of THP-1 cells to both uremic toxins resulted in the upregulation of BMP-2 and miRNAs-126-3p, -146b-5p, and -223-3p, as well as the activation of nuclear factor kappa B (NF-κB) and a decrease in its inhibitor IĸB. Uremic toxins, such as IS and PC, enhance the migratory and adhesion capacity of THP-1 cells to the vascular endothelium. These toxins, particularly PC, contribute significantly to uremia-associated vascular disease by increasing in THP-1 cells the expression of BMP-2, NF-κB, and key miRNAs associated with the development of atherosclerotic vascular diseases.


Asunto(s)
Aterosclerosis , MicroARNs , Humanos , Tóxinas Urémicas , Células Endoteliales , Monocitos , FN-kappa B , Aterosclerosis/genética , Indicán/toxicidad , MicroARNs/genética , Adherencias Tisulares
4.
Am J Physiol Renal Physiol ; 312(4): F673-F681, 2017 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-28077371

RESUMEN

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+ and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.


Asunto(s)
Angiopoyetina 1/sangre , Angiopoyetina 2/sangre , Micropartículas Derivadas de Células/metabolismo , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/terapia , Células Endoteliales/metabolismo , Diálisis Renal , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/terapia , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Micropartículas Derivadas de Células/patología , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/mortalidad , Progresión de la Enfermedad , Células Endoteliales/patología , Femenino , Humanos , Mediadores de Inflamación/sangre , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Valor Predictivo de las Pruebas , Prevalencia , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/mortalidad , España/epidemiología , Factores de Tiempo , Resultado del Tratamiento
5.
Kidney Int ; 92(5): 1084-1099, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28760336

RESUMEN

Although magnesium has been shown to prevent vascular calcification in vitro, controlled in vivo studies in uremic animal models are limited. To determine whether dietary magnesium supplementation protects against the development of vascular calcification, 5/6 nephrectomized Wistar rats were fed diets with different magnesium content increasing from 0.1 to 1.1%. In one study we analyzed bone specimens from rats fed 0.1%, 0.3%, and 0.6% magnesium diets, and in another study we evaluated the effect of intraperitoneal magnesium on vascular calcification in 5/6 nephrectomized rats. The effects of magnesium on established vascular calcification were also evaluated in uremic rats fed on diets with either normal (0.1%) or moderately increased magnesium (0.6%) content. The increase in dietary magnesium resulted in a marked reduction in vascular calcification, together with improved mineral metabolism and renal function. Moderately elevated dietary magnesium (0.3%), but not high dietary magnesium (0.6%), improved bone homeostasis as compared to basal dietary magnesium (0.1%). Results of our study also suggested that the protective effect of magnesium on vascular calcification was not limited to its action as an intestinal phosphate binder since magnesium administered intraperitoneally also decreased vascular calcification. Oral magnesium supplementation also reduced blood pressure in uremic rats, and in vitro medium magnesium decreased BMP-2 and p65-NF-κB in TNF-α-treated human umbilical vein endothelial cells. Finally, in uremic rats with established vascular calcification, increasing dietary magnesium from 0.1% magnesium to 0.6% reduced the mortality rate from 52% to 28%, which was associated with reduced vascular calcification. Thus, increasing dietary magnesium reduced both vascular calcification and mortality in uremic rats.


Asunto(s)
Huesos/metabolismo , Suplementos Dietéticos , Magnesio/administración & dosificación , Fosfatos/metabolismo , Uremia/complicaciones , Calcificación Vascular/dietoterapia , Animales , Quelantes/administración & dosificación , Modelos Animales de Enfermedad , Células Endoteliales de la Vena Umbilical Humana , Humanos , Magnesio/sangre , Masculino , Nefrectomía , Ratas , Ratas Wistar , Uremia/sangre , Uremia/dietoterapia , Calcificación Vascular/sangre , Calcificación Vascular/mortalidad
6.
Heart Vessels ; 32(11): 1390-1399, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28623398

RESUMEN

Coronary heart disease is associated with high morbidity and mortality. Endothelial dysfunction in affected patients is linked to long-term atherosclerotic disease progression and cardiovascular event rates. The present paper reports on changes in the levels of endothelial progenitor cells (VEGFR2/CD133/CD34), essential for endothelial repair, and of endothelial microvesicles (CD31/annexin V) as indicators of endothelial lesion, in patients undergoing coronary bypass surgery with respect both to baseline levels and to counts in healthy subjects. In an observational descriptive study, 31 patients scheduled for coronary revascularization surgery were compared with those of 25 healthy controls. In a subsequent longitudinal study, patients undergoing surgery were monitored at 5 timepoints up until 48 h after surgery. Endothelial progenitor cell (VEGFR2/CD133/CD34) and endothelial microvesicle (CD31/annexin V) levels were quantified by flow cytometry. Baseline endothelial progenitor cell counts in coronary patients were significantly lower than those of healthy controls (p < 0.001); however, after surgery, levels rose steadily over all 5 timepoints to 48 h  with statistically significant differences (p < 0.001) between intra-operative and 48 h after surgery (T5). Endothelial microvesicle levels were significantly higher in coronary patients prior to surgery than in healthy controls (p < 0.001), and despite declining at 48 h remained significantly higher than those of controls (p < 0.001). Coronary surgery has had a positive impact on the endothelium in the patients, prompting a decrease in signs of endothelial dysfunction and a considerable improvement in the endothelial repair mechanisms involved in angiogenesis, playing an important role in the inflammatory response and the remodelling process of ischemic myocardium in postoperative period.


Asunto(s)
Anexinas/sangre , Enfermedad de la Arteria Coronaria/sangre , Vasos Coronarios/metabolismo , Endotelio Vascular/metabolismo , Revascularización Miocárdica , Vasodilatación/fisiología , Biomarcadores/sangre , Micropartículas Derivadas de Células/metabolismo , Micropartículas Derivadas de Células/patología , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/cirugía , Vasos Coronarios/fisiopatología , Vasos Coronarios/cirugía , Células Progenitoras Endoteliales/metabolismo , Células Progenitoras Endoteliales/patología , Endotelio Vascular/patología , Endotelio Vascular/fisiopatología , Citometría de Flujo , Estudios de Seguimiento , Humanos , Periodo Posoperatorio , Pronóstico , Estudios Prospectivos
7.
Rev Med Chil ; 143(4): 459-66, 2015 Apr.
Artículo en Español | MEDLINE | ID: mdl-26204537

RESUMEN

BACKGROUND: Frailty is not universal among older people but increases the risk of dependence. AIM: To assess frailty among older people and its relationship with biological, psychological and social factors. MATERIAL AND METHODS: Seven hundred fifty four older people aged 73 ± 6 years (61% females), attending a public primary care were assessed. Frailty was defined according to Fried criteria that considers inexplicable weight loss, tiredness, muscle weakness and lack of physical activity. RESULTS: Absence of frailty, pre-frailty and frailty was found in 26, 69 and 5% of participants, respectively. Significant differences between frailty groups were observed for age, gender, years of studies, minimental and self-efficacy scores. Among participants defined as being in a pre-frail condition, 59% were non-disabled without risk and 41% non-disabled in risk, according to the functional assessment for older people used in Chilean primary care clinics. CONCLUSIONS: Frailty among older people is associated with increasing age, education, cognitive status and self-efficacy.


Asunto(s)
Anciano Frágil/estadística & datos numéricos , Evaluación Geriátrica/estadística & datos numéricos , Atención Primaria de Salud/estadística & datos numéricos , Factores de Edad , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Chile , Complicaciones de la Diabetes , Fatiga/diagnóstico , Femenino , Anciano Frágil/psicología , Humanos , Hipertensión/complicaciones , Masculino , Actividad Motora/fisiología , Fuerza Muscular/fisiología , Debilidad Muscular/diagnóstico , Debilidad Muscular/psicología , Factores Socioeconómicos , Encuestas y Cuestionarios , Incontinencia Urinaria/complicaciones , Pérdida de Peso/fisiología
8.
Am J Physiol Renal Physiol ; 307(11): F1302-11, 2014 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-25339701

RESUMEN

Vascular calcification (VC) is a frequent complication of chronic kidney disease (CKD) and is a predictor of cardiovascular morbidity and mortality. In the present study, we investigated the potential involvement of endothelial microparticles (MPs) and endothelial progenitor cells (EPCs) in the generation of VC in CKD patients. The number of circulating EMPs is greater in patients with VC than without VC (307 ± 167 vs. 99 ± 75 EMPs/µl, P < 0.001). The percentage of EPCs is significantly lower in patient with VC than in patients without VC (0.14 ± 0.11% vs. 0.25 ± 0.18%, P = 0.002). The number of EPCs expressing osteocalcin (OCN) was higher in VC patients (349 ± 63 cells/100,000) than in non-VC patients (139 ± 75 cells/100,000, P < 0.01). In vitro, MPs obtained from CKD patients were able to induce OCN expression in EPCs from healthy donors; the increase in OCN expression was more accentuated if MPs were obtained from CKD patients with VC. MPs from CKD patients also induced OCN expression in vascular smooth muscle cells and fibroblasts. In CKD patients, the rise in endothelial MPs associated with a decrease in the number of EPCs, suggesting an imbalance in the processes of endothelial damage and repair in CKD patients, mainly those with VC. Our results suggest that EPCs, through OCN expression, may directly participate in the process of VC.


Asunto(s)
Calcinosis/patología , Endotelio Vascular/patología , Insuficiencia Renal Crónica/patología , Anciano , Anexina A5/biosíntesis , Anexina A5/genética , Calcinosis/metabolismo , Capilares/fisiología , Micropartículas Derivadas de Células/metabolismo , Micropartículas Derivadas de Células/patología , Endotelio Vascular/metabolismo , Femenino , Fibroblastos/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/biosíntesis , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Cultivo Primario de Células , Insuficiencia Renal Crónica/metabolismo , Células Madre/patología
9.
Rev Esc Enferm USP ; 58: e20230417, 2024.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-38767848

RESUMEN

The objective of the study was to identify the main challenges in conducting research with immigrants and refugees and to provide seven methodological and pragmatic strategies. The analyses presented, based on the Theory of Culture Care Diversity and Universality, are extracted from insights of the authors' experiences as researchers and the literature. The main challenges are related to cultural, moral, political, and educational differences between researcher and researched; identification of the universe and sampling; access to informants through the barrier of distrust; and communication and language difficulties. Strategies to make research more successful involve: developing a thorough research protocol; creatively recruiting participants; developing strategies to facilitate communication; having a sensitive look; offering a structure of reciprocity; increasing trust, and triangulating research. The main methodological and pragmatic issues in studies with immigrants and refugees were explored, providing valuable guidance for future projects. However, in different migration situations, researchers must be aware of the possibility of other challenges arising during the investigative process.


Asunto(s)
Emigrantes e Inmigrantes , Investigación en Enfermería , Refugiados , Humanos , Investigación en Enfermería/métodos
10.
Nanoscale Horiz ; 8(12): 1700-1710, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37819240

RESUMEN

A selenium-containing metal-organic framework with remarkable antioxidant capacity and ROS-scavenging activity was constructed by a controlled de novo encapsulation approach of a glycoconjugate mimetic, specifically a sp2-iminoglycolipid bearing a selenoureido fragment (DSeU), within a zeolitic-imidazolate framework exoskeleton. Biocompatible and homogeneous nanosized particles of ∼70 nm (DSeU@ZIF8) were obtained, which could be efficiently internalized in cells, overcoming the poor solubility in biological media and limited bioavailability of glycolipids. The ZIF-particle served as nanocarrier for the intracellular delivery of the selenocompound to cells, promoted by the acidic pH inside endosomes/lysosomes. As demonstrated by in vitro studies, the designed DSeU@ZIF8 nanoparticles displayed a high antioxidant activity at low doses; lower intracellular ROS levels were observed upon the uptake of DSeU@ZIF8 by human endothelial cells. Even more interesting was the finding that these DSeU@ZIF8 particles were able to reverse to a certain level the oxidative stress induced in cells by pre-treatment with an oxidizing agent. This possibility of modulating the oxidative stress in living cells may have important implications in the treatment of diverse pathological complications that are generally accompanied with elevated ROS levels.


Asunto(s)
Antioxidantes , Nanopartículas , Humanos , Antioxidantes/uso terapéutico , Células Endoteliales , Especies Reactivas de Oxígeno , Estrés Oxidativo
11.
Artículo en Inglés | MEDLINE | ID: mdl-34201913

RESUMEN

The aim of this research was to evaluate the mediating effect of the value orientations of collectivism and individualism on the relationship between ethnic identity and well-being, the latter conceived from the worldview of Andean natives. For this purpose, under an observational and cross-sectional design, 395 Lickan-Antay adults (57% women) living in areas of indigenous development and in two cities in northern Chile were surveyed. We used the Lickan-Antay BLA32 well-being scale, a short version of the Portrait 21 Values Questionnaire to measure individualistic and collectivistic values, and an adapted version of the Ethnic Identity Scale. The results show that ethnic identity had a direct positive effect on all three dimensions of well-being (harmony with community life, ethnic harmony and harmony with nature), and total indirect effects on all five dimensions of well-being, one of them originating mainly from collectivist orientations. Individualistic orientations also showed a positive, though less intense, mediating effect on well-being. We conclude that collectivist and individualistic motivational patterns coexist in Lickan-Antay natives and explain an important part of the relationship between ethnic identity and well-being. Finally, we discuss our results and suggest replication of this study in other ethnic contexts to assess the generalizability of these findings to other native peoples of the Andean region of South America.


Asunto(s)
Motivación , Valores Sociales , Adulto , Chile , Estudios Transversales , Femenino , Humanos , Pueblos Indígenas , Masculino
12.
Toxins (Basel) ; 13(10)2021 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-34679030

RESUMEN

Endothelial aging may be induced early in pathological situations. The uremic toxins indoxyl sulfate (IS) and p-cresol (PC) accumulate in the plasma of chronic kidney disease (CKD) patients, causing accelerated endothelial aging, increased cardiovascular events and mortality. However, the mechanisms by which uremic toxins exert their deleterious effects on endothelial aging are not yet fully known. Thus, the aim of the present study is to determine the effects of IS and PC on endothelial damage and early senescence in cultured human umbilical vein endothelial cells (HUVECs). Hence, we establish an in vitro model of endothelial damage mediated by different passages of HUVECs and stimulated with different concentrations of IS and PC to evaluate functional effects on the vascular endothelium. We observe that cell passage-induced senescence is associated with apoptosis, ROS production and decreased endothelial proliferative capacity. Similarly, we observe that IS and PC cause premature aging in a dose-dependent manner, altering HUVECs' regenerative capacity, and decreasing their cell migration and potential to form vascular structures in vitro. In conclusion, IS and PC cause accelerated aging in HUVECs, thus contributing to endothelial dysfunction associated with CKD progression.


Asunto(s)
Senescencia Celular/efectos de los fármacos , Cresoles/toxicidad , Indicán/toxicidad , Envejecimiento , Movimiento Celular/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Insuficiencia Renal Crónica
13.
Eur Heart J Case Rep ; 4(3): 1-4, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32617470

RESUMEN

BACKGROUND: We present a complex case of a failing tricuspid mechanical valve prosthesis in a patient with refractory cardiogenic shock at prohibitive risk for surgery in whom balloon 'valvuloplasty' resulted in immediate haemodynamic improvement in valve function. CASE SUMMARY: A 67-year-old woman with remote history of endocarditis s/p tricuspid valve repair and mechanical aortic valve replacement was referred for second opinion and management of new severe symptomatic tricuspid valve stenosis resulting in progressive debilitating congestive heart failure (HF). The patient was approved by the heart team to undergo redo open heart for surgical repair of the tricuspid valve. Intraoperative technical challenges were met to repair the tricuspid valve. In turn, the native valve was resected and a 33 mm On-X mechanical valve prosthesis. The patient's post-operative course was complicated by recurrent haemoptysis, prolonged mechanical respiratory support, acute kidney injury, and cardiogenic shock. Surgical re-exploration to address the dysfunctional mechanical tricuspid valve was felt to be prohibitive. Structural heart team was consulted. Cardiac catheterization was recommended to ascertain and confirm findings. The patient was transferred to the cardiac catheterization laboratory. Initial fluoroscopic examination of the heart confirmed the echocardiographic results of an immobile septal leaflet of the recently implanted mechanical tricuspid valve. An 8 × 40 mm Mustang OTW angioplasty balloon was then advanced across the mechanical valve and inflated gradually at nominal pressure. A single inflation resulted in successful restoration of valve leaflet function. DISCUSSION: To the best of our knowledge, this is the first balloon 'valvuloplasty' on a mechanical On-X valve in the tricuspid position.

14.
Sci Rep ; 10(1): 10657, 2020 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-32606426

RESUMEN

Protein bound uremic toxins, such as p-cresol, cannot be effectively removed by conventional dialysis techniques and are accumulated in plasma, thus contributing to progression of both chronic kidney disease (CKD) and cardiovascular disease (CVD). Pathological effects of uremic toxins include activation of inflammatory response, endothelial dysfunction and release of endothelial microvesicles. To date, the role of p-cresol in endothelial microvesicles formation has not been analyzed. The aim of the present study was evaluate the effects of endothelial microvesicles released by p-cresol (PcEMV) on endothelial dysfunction. An in vitro model of endothelial damage mediated by p-cresol was proposed to evaluate the functional effect of PcEMV on the endothelial repair process carried out by endothelial cells and microRNA (miRNA) that could be involved in this process. We observed that p-cresol induced a greater release of microvesicles in endothelial cells. These microvesicles altered regenerative capacity of endothelial cells, decreasing their capacity for cell migration and their potential to form vascular structures in vitro. Moreover, we observed increased cellular senescence and a deregulation of miRNA-146b-5p and miRNA-223-3p expression in endothelial cells treated with endothelial microvesicles released by p-cresol. In summary our data show that microvesicles generated in endothelial cells treated with p-cresol (PcEMV) interfere with the endothelial repair process by decreasing the migratory capacity, the ability to form new vessels and increasing the senescence of mature endothelial cells. These alterations could be mediated by the upregulation of miRNA-146b-5p and miRNA-223-3p.


Asunto(s)
Cresoles/toxicidad , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Microvasos/efectos de los fármacos , Microvasos/metabolismo , Enfermedades Vasculares/inducido químicamente , Enfermedades Vasculares/metabolismo , Movimiento Celular/efectos de los fármacos , Micropartículas Derivadas de Células/efectos de los fármacos , Micropartículas Derivadas de Células/metabolismo , Células Cultivadas , Senescencia Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , MicroARNs/metabolismo , Toxinas Biológicas/toxicidad , Regulación hacia Arriba/efectos de los fármacos , Uremia/metabolismo
15.
Front Cell Dev Biol ; 8: 739, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32850849

RESUMEN

BACKGROUND: Patients with chronic kidney disease (CKD) show a chronic microinflammatory state that promotes premature aging of the vascular system. Currently, there is a growth interest in the search of novel biomarkers related to vascular aging to identify CKD patients at risk to develop cardiovascular complications. METHODS: Forty-five CKD patients were divided into three groups according to CKD-stages [predialysis (CKD4-5), hemodialysis (HD) and kidney transplantation (KT)]. In all these patients, we evaluated the quantitative changes in microRNAs (miRNAs), CD14+C16++ monocytes number, and microvesicles (MV) concentration [both total MV, and monocytes derived MV (CD14+Annexin V+CD16+)]. To understand the molecular mechanism involved in senescence and osteogenic transdifferentation of vascular smooth muscle cells (VSMC), these cells were stimulated with MV isolated from THP-1 monocytes treated with uremic toxins (txMV). RESULTS: A miRNA array was used to investigate serum miRNAs profile in CKD patients. Reduced expression levels of miRNAs-126-3p, -191-5p and -223-3p were observed in CKD4-5 and HD patients as compared to KT. This down-regulation disappeared after KT, even when lower glomerular filtration rates (eGFR) persisted. Moreover, HD patients had higher percentage of proinflammatory monocytes (CD14+CD16++) and MV derived of proinflammatory monocytes (CD14+Annexin V+CD16+) than the other groups. In vitro studies showed increased expression of osteogenic markers (BMP2 and miRNA-223-3p), expression of cyclin D1, ß-galactosidase activity and VSMC size in those cells treated with txMV. CONCLUSION: CKD patients present a specific circulating miRNAs expression profile associated with the microinflammatory state. Furthermore, microvesicles generated by monocytes treated with uremic toxins induce early senescence and osteogenic markers (BMP2 and miRNA-223-3p) in VSMC.

16.
PLoS One ; 14(2): e0212547, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30794611

RESUMEN

Pancreatic autoantibodies (AAb) has been associated with a worse pancreas graft survival after simultaneous pancreas-kidney transplantation (SPK). However, due to the variable time for AAb to become positive and the lack of early biomarkers suggesting such autoimmune activation, the mechanisms leading ß-cell destruction remain uncertain. The present study aimed to evaluate the association between post-transplant AAb and the functional impairment of the pancreatic ß-cell and also the association of such AAb with inflammation after SPK. In a longitudinal study, we analyzed the impact of post-transplant glutamic acid decarboxylase (GAD-65) and the insulinoma-associated autoantigen 2 (IA-2) AAb on pancreas graft function. Serum Hb1Ac and C-peptide (C-pep) were longitudinally compared between a group with positive posttransplant AAb (AAb+; n = 40) and another matched group with negative AAb (AAb-; n = 40) until the fifth year following seroconversion. In the cross-sectional analysis, we further evaluated the systemic signatures of inflammation by measuring pro-inflammatory CD14+CD16+ monocytes by flow-cytometry and interleukin 17-A serum levels in 38 SPK recipients and ten healthy controls. In the longitudinal study, patients with AAb+ showed higher levels of Hb1Ac (p<0.001) and lower C-pep levels (p<0.001) compared to those who remained AAb- throughout the follow-up. In the cross-sectional study, AAb+ patients showed a higher percentage of CD14+CD16+ monocytes compared with those with AAb- and the healthy controls (6.70±4.19% versus 4.0±1.84% and 3.44±0.93%; p = 0.026 and 0.009 respectively). Also, CD14+CD16+ monocytes correlated with Hb1Ac and C-pep serum levels. Multivariate logistic regression showed that posttransplant AAb+ was independently associated with a higher percentage of pro-inflammatory monocytes (adjusted-OR 1.59, 95%CI 1.05-2.40, p = 0.027). The group of patients with positive AAb also showed higher levels of IL17A as compared with the other groups (either healthy control or the negative AAb subjects). In conclusion, pancreatic AAb+ after SPK were not only associated with higher Hb1Ac and lower c-peptide serum levels but also with an increased percentage of CD14+CD16+ monocytes and higher levels of circulating IL17-A.


Asunto(s)
Autoanticuerpos , Linfocitos B , Trasplante de Riñón , Monocitos , Páncreas , Adulto , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Autoantígenos/sangre , Autoantígenos/inmunología , Linfocitos B/inmunología , Linfocitos B/metabolismo , Linfocitos B/patología , Estudios Transversales , Femenino , Humanos , Recuento de Leucocitos , Estudios Longitudinales , Masculino , Monocitos/inmunología , Monocitos/metabolismo , Monocitos/patología , Páncreas/inmunología , Páncreas/metabolismo , Páncreas/patología , Trasplante de Páncreas
17.
Astrophys J Lett ; 879(1)2019 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-31428298

RESUMEN

AB Aur is a Herbig Ae star hosting a well-known transitional disk. Because of its proximity and low inclination angle, it is an excellent object to study planet formation. Our goal is to investigate the chemistry and dynamics of the molecular gas component in the AB Aur disk, and its relation with the prominent horseshoe shape observed in continuum mm emission. We used the NOEMA interferometer to map with high angular resolution the J = 3-2 lines of HCO+ and HCN. By combining both, we can gain insight into the AB Aur disk structure. Chemical segregation is observed in the AB Aur disk: HCO+ shows intense emission toward the star position, at least one bright molecular bridge within the dust cavity, and ring-like emission at larger radii, while HCN is only detected in an annular ring that is coincident with the dust ring and presents an intense peak close to the dust trap. We use HCO+ to investigate the gas dynamics inside the cavity. The observed bright HCO+ bridge connects the compact central source with the outer dusty ring. This bridge can be interpreted as an accretion flow from the outer ring to the inner disk/jet system proving gas accretion through the cavity.

18.
Rev. Esc. Enferm. USP ; 58: e20230417, 2024. graf
Artículo en Inglés | LILACS-Express | LILACS, BDENF | ID: biblio-1559057

RESUMEN

ABSTRACT The objective of the study was to identify the main challenges in conducting research with immigrants and refugees and to provide seven methodological and pragmatic strategies. The analyses presented, based on the Theory of Culture Care Diversity and Universality, are extracted from insights of the authors' experiences as researchers and the literature. The main challenges are related to cultural, moral, political, and educational differences between researcher and researched; identification of the universe and sampling; access to informants through the barrier of distrust; and communication and language difficulties. Strategies to make research more successful involve: developing a thorough research protocol; creatively recruiting participants; developing strategies to facilitate communication; having a sensitive look; offering a structure of reciprocity; increasing trust, and triangulating research. The main methodological and pragmatic issues in studies with immigrants and refugees were explored, providing valuable guidance for future projects. However, in different migration situations, researchers must be aware of the possibility of other challenges arising during the investigative process.


RESUMEN El objetivo del estudio fue identificar los principales desafíos al realizar investigaciones con inmigrantes y refugiados y proporcionar siete estrategias metodológicas y pragmáticas. Los análisis presentados, basados en la Teoría de Diversidad y Universalidad de la Atención Cultural, se extraen de insights de las experiencias de los autores como investigadores y de la literatura. Los principales desafíos están relacionados con las diferencias culturales, morales, políticas y educativas entre investigador e investigado; identificación del universo y muestreo; acceso a informantes a través de la barrera de la desconfianza; y dificultades de comunicación y lenguaje. Las estrategias para lograr que la investigación sea más exitosa implican: desarrollar un protocolo de investigación exhaustivo; reclutar participantes de forma creativa; desarrollar estrategias para facilitar la comunicación; tener una mirada sensible; ofrecer una estructura de reciprocidad; aumentar la confianza y triangular la investigación. Se exploraron las principales cuestiones metodológicas y pragmáticas en los estudios con inmigrantes y refugiados, proporcionando una valiosa orientación para proyectos futuros. Sin embargo, en diferentes situaciones migratorias, los investigadores deben ser conscientes de la posibilidad de que surjan otros desafíos durante el proceso de investigación.


RESUMO O objetivo do estudo foi identificar os principais desafios na condução de pesquisas com imigrantes e refugiados e fornecer sete estratégias metodológicas e pragmáticas. As análises apresentadas, embasadas na Teoria da Diversidade e Universalidade do Cuidado Cultural, são extraídas de insights das experiências dos autores enquanto pesquisadores e da literatura. Os principais desafios relacionam-se a diferenças culturais, morais, políticas e educacionais entre pesquisador e pesquisado; identificação do universo e amostragem; acesso aos informantes pela barreira da desconfiança; e dificuldade de comunicação e idioma. As estratégias para tornar a pesquisa mais exitosa envolvem: desenvolver um minucioso protocolo de pesquisa; recrutar participantes de forma criativa; elaborar estratégias para facilitar a comunicação; ter olhar sensível; oferecer uma estrutura de reciprocidade; ampliar a confiança e triangular a pesquisa. Foram exploradas as principais questões metodológicas e pragmáticas nos estudos com imigrantes e refugiados, fornecendo orientações valiosas para projetos futuros. Entretanto, em diferentes situações de migração, os pesquisadores devem atentar-se para a possibilidade de surgirem outros desafios durante o processo investigativo.

19.
Nefrologia (Engl Ed) ; 38(1): 41-47, 2018.
Artículo en Inglés, Español | MEDLINE | ID: mdl-28673686

RESUMEN

INTRODUCTION: Patients on haemodialysis (HD) have a high prevalence of 25-OH-vitamin D (25-OH-D)deficiency. Secondary hyperparathyroidismis a common condition in these patients, which is very important to control. 25-OH-D is involved in regulating calcium homeostasis. As such, appropriate levels of this vitamin could help to control bone mineral metabolism. OBJECTIVE: To evaluate the effect 25-OH-D repletion in HD patients with 25-OH-D deficiency (<20ng/ml) on the control of secondary hyperparathyroidism and microinflammation status. PATIENTS AND METHODS: Prospective observational study in which stable patients on HD with 25-OH-D deficiency (<20ng/ml) were treated with oral calcifediol 0.266mcg/every 2 weeks for three months. Dialysis characteristics, biochemical parameters and drug doses administered were analysed before and after the correction of the deficiency. RESULTS: Forty-five stable HD patients with a mean age of 74.08±12.49 years completed treatment. Twenty-seven patients (60%) achieved 25-OH-D levels above 20ng/ml (23 with levels>30ng/ml and 4 between 20-30ng/ml). Parathyroid hormone levels decreased in 32 of the 45 patients, 23 of which (51%) achieved a>30% decrease from baseline. In terms of concomitant treatment, we observed a significant reduction in the selective vitamin D receptor activator dose, but no changes in calcimimetic or phosphate binders administration. In terms of malnutrition-inflammation status, a decrease in C-reactive protein was noted, although other microinflammation parameters, such as activated monocytes (CD14+/CD16+ and CD 14++/CD16+) were unchanged. No changes were observed in the levels of FGF-23. CONCLUSIONS: Correcting 25-OH-D deficiency in HD patients is associated with better secondary hyperparathyroidism control with lower doses of vitamin D analogues, as well as an improvement in inflammatory status. Our results support the recommendation to determine 25-OH-D levels and correct its deficiency in these patients.


Asunto(s)
Calcifediol/uso terapéutico , Hiperparatiroidismo Secundario/tratamiento farmacológico , Diálisis Renal , Deficiencia de Vitamina D/tratamiento farmacológico , Vitamina D/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Calcio/metabolismo , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Homeostasis , Humanos , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/etiología , Inflamación , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Estudios Prospectivos , Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones
20.
Horiz. enferm ; 34(1): 35-49, 2023. ilus, tab
Artículo en Español | LILACS | ID: biblio-1427983

RESUMEN

OBJETIVO: Determinar el efecto mediador de la motivación a buscar venganza en la relación de la ansiedad y la evitación en el apego con la calidad de vida. METODOLOGÍA: estudio transversal correlacional. La muestra estuvo constituida por 558 personas de 18 a 65 años de la ciudad de Antofagasta, Chile. Fueron utilizados los instrumentos: Cuestionario WHOQoL-Bref; Experiencia en Relaciones Cercanas; y Motivación a buscar venganza. Se realizó un modelo de ecuaciones estructurales que consideró efectos directos, indirectos y totales. RESULTADOS: Del total de participantes, 289 (51,8%) fueron hombres. Las edades fluctuaron entre 18 y 65 años (M=39,7; ±13,42). Se encontraron efectos significativos en la relación entre la ansiedad y evitación en el apego en los dominios físico, psicológico y social-relacional de la calidad de vida. La motivación a buscar venganza tiene efecto de mediación total en la relación entre evitación en el apego y el dominio físico, y efecto de mediación parcial de la evitación en el apego sobre el dominio psicológico de la calidad de vida. CONCLUSIÓN: ansiedad y evitación en el apego disminuyen la calidad de vida y la motivación a buscar venganza media parcial o totalmente la relación entre la evitación en el apego sobre los dominios físico y psicológico de la calidad de vida.


OBJECTIVE: To determine the mediating effect of revenge-seeking motivation on the relationship between anxiety and avoidance in attachment and quality of life. METHODOLOGY: cross-sectional correlational study. The sample consisted of 558 people aged 18 to 65 years from the city of Antofagasta, Chile. The following instruments were used: WHOQoL-Bref Questionnaire; Experience in Close Relationships; and Motivation to seek revenge. Structural equation modeling was performed considering direct, indirect and total effects. RESULTS: Of the total number of participants, 289 (51.8%) were male. Ages ranged from 18 to 65 years (M=39.7; ±13.42). Significant effects were found in the relationship between anxiety and avoidance on attachment in the physical, psychological, and social-relational domains of quality of life. Revenge-seeking motivation has full mediation effect on the relationship between attachment avoidance and the physical domain, and partial mediation effect of attachment avoidance on the psychological domain of quality of life. CONCLUSION: Anxiety and attachment avoidance decrease quality of life, and revenge-seeking motivation partially or fully mediates the relationship between attachment avoidance and the physical and psychological domains of quality of life.


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Ansiedad/psicología , Calidad de Vida/psicología , Salud Mental , Psicoterapia , Chile , Bienestar Psicológico , Hombres/psicología
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