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1.
Ecotoxicol Environ Saf ; 282: 116732, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39018733

RESUMEN

Process affected water and other industrial wastewaters are a major environmental concern. During oil sands mining, large amounts of oil sands process affected water (OSPW) are generated and stored in ponds until reclaimed and ready for surface water discharge. While much research has focused on organics in process waters, trace metals at high concentrations may also pose environmental risks. Phytoremediation is a cost effective and sustainable approach that employs plants to extract and reduce contaminants in water. The research was undertaken in mesocosm scale constructed wetlands with plants exposed to OSPW for 60 days. The objective was to screen seven native emergent wetland species for their ability to tolerate high metal concentrations (arsenic, cadmium, copper, chromium, copper, nickel, selenium, zinc), and then to evaluate the best performing species for OSPW phytoremediation. All native plant species, except Glyceria grandis, tolerated and grew in OSPW. Carex aquatilis (water sedge), Juncus balticus (baltic rush), and Typha latifolia (cattail) had highest survival and growth, and had high metal removal efficiencies for arsenic (81-87 %), chromium (78-86 %), and cadmium (74-84 %), relative to other metals; and greater than 91 % of the dissolved portions were removed. The native plant species were efficient accumulators of all metals, as demonstrated by high root and shoot bioaccumulation factors; root accumulation was greater than shoot accumulation. Translocation factor values were greater than one for Juncus balticus (chromium, zinc) and Carex aquatilis (cadmium, chromium, cobalt, nickel). The results demonstrate the potential suitability of these species for phytoremediation of a number of metals of concern and could provide an effective and environmentally sound remediation approach for wastewaters.


Asunto(s)
Biodegradación Ambiental , Aguas Residuales , Contaminantes Químicos del Agua , Humedales , Contaminantes Químicos del Agua/metabolismo , Aguas Residuales/química , Metales Pesados/metabolismo , Yacimiento de Petróleo y Gas , Minería , Arsénico/metabolismo , Cadmio/metabolismo , Residuos Industriales , Typhaceae/metabolismo , Plantas/metabolismo , Metales/metabolismo
2.
Chemosphere ; 361: 142375, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38772514

RESUMEN

Oil sands process affected water (OSPW) is produced during bitumen extraction and typically contains high concentrations of trace metals. Constructed wetlands have emerged as a cost effective and green technology for the treatment of metals in wastewaters. Whether the addition of amendments to constructed wetlands can improve metal removal efficiency is unknown. We investigated the synergistic effects of carbon based amendments and wetland plant species in removal of arsenic, cadmium, cobalt, chromium, copper, nickel, and selenium from OSPW. Three native wetland species (Carex aquatilis, Juncus balticus, Scirpus validus) and two amendments (canola straw biochar, nano humus) were investigated in constructed wetland mesocosms over 60 days. Amendment effect on metal removal efficiency was not significant, while plant species effect was. Phytoremediation resulted in removal efficiencies of 78.61-96.31 % for arsenic, cadmium, and cobalt. Carex aquatilis had the highest removal efficiencies for all metals. Amendments alone performed well in removing some metals and were comparable to phytoremediation for cadmium, cobalt, copper, and nickel. Metals were primarily distributed in roots with negligible translocation to shoots. Our work provides insights into the role of plants and amendments during metal remediation and their complex interactions in constructed treatment wetlands.


Asunto(s)
Biodegradación Ambiental , Carbón Orgánico , Sustancias Húmicas , Contaminantes Químicos del Agua , Humedales , Carbón Orgánico/química , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/análisis , Metales Pesados/metabolismo , Metales Pesados/análisis , Arena , Aguas Residuales/química , Metales/metabolismo , Arsénico/metabolismo , Arsénico/análisis , Hidrocarburos/metabolismo
4.
Sci Total Environ ; 880: 163115, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37011671

RESUMEN

Effectiveness of constructed floating wetlands (CFWs) is largely unknown for wastewater treatment in cold climates. An operational-scale CFW system was retrofitted into a municipal waste stabilization pond in Alberta, Canada. During the first year (Study I), insignificant performance was recorded for water quality parameters, although phyto-uptake of elements was evident. In Study II, doubling of the CFW area and addition of underneath aeration promoted plant uptake of elements, including nutrients and metals, following significant pollutant reduction in the water; 83 % of chemical oxygen demand, 80 % of carbonaceous biochemical oxygen demand, 67 % of total suspended solids, and 48 % of total Kjeldhal nitrogen. A mesocosm study, conducted in parallel to the pilot scale field study, confirmed the impact of both vegetation and aeration on water quality improvement. The phytoremediation potential was linked to accumulation within plant shoot and root biomass and was confirmed by mass balance. Bacterial community analyses reflected that heterotrophic nitrification, aerobic denitrification, complete denitrification, organic matter decomposition, and methylotrophy were dominant mechanisms in the CFW, likely resulting in successful transformation of organics and nutrients. CFWs appear to be a viable ecotechnology to treat municipal wastewater in Alberta; however, larger and aerated CFW systems are recommended to achieve maximum remediation. The study aligns with the United Nations Environment Program to scale up restoration of degraded ecosystems, and to improve conditions for water supply and biodiversity following recognition of 2021-2030 as the Decade on Ecosystem Restoration.


Asunto(s)
Ecosistema , Humedales , Clima Frío , Estanques , Alberta , Eliminación de Residuos Líquidos/métodos , Nitrógeno/metabolismo , Análisis de la Demanda Biológica de Oxígeno
5.
J Integr Complement Med ; 29(11): 695-704, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37102680

RESUMEN

Introduction: Long COVID is a term that encompasses a range of signs, symptoms, and sequalae that continue or develop after an acute COVID-19 infection. The lack of early recognition of the condition contributed to delays in identifying factors that may contribute toward its development and prevention. The aim of this study was to scope the available literature to identify potential nutritional interventions to support people with symptoms associated with long COVID. Methods: This study was designed as a systematic scoping review of the literature (registration PROSPERO CRD42022306051). Studies with participants aged 18 years or older, with long COVID and who underwent a nutritional intervention were included in the review. Results: A total of 285 citations were initially identified, with five papers eligible for inclusion: two were pilot studies of nutritional supplements in the community, and three were nutritional interventions as part of inpatient or outpatient multidisciplinary rehabilitation programs. There were two broad categories of interventions: those that focused on compositions of nutrients (including micronutrients such as vitamin and mineral supplements) and those that were incorporated as part of multidisciplinary rehabilitation programs. Nutrients included in more than one study were multiple B group vitamins, vitamin C, vitamin D, and acetyl-l-carnitine. Discussion: Two studies trialed nutritional supplements for long COVID in community samples. Although these initial reports were positive, they are based on poorly designed studies and therefore cannot provide conclusive evidence. Nutritional rehabilitation was an important aspect of recovery from severe inflammation, malnutrition, and sarcopenia in hospital rehabilitation programs. Current gaps in the literature include a potential role for anti-inflammatory nutrients such as the omega 3 fatty acids, which are currently undergoing clinical trials, glutathione-boosting treatments such as N-acetylcysteine, alpha-lipoic acid, or liposomal glutathione in long COVID, and a possible adjunctive role for anti-inflammatory dietary interventions. This review provides preliminary evidence that nutritional interventions may be an important part of a rehabilitation program for people with severe long COVID symptomatology, including severe inflammation, malnutrition, and sarcopenia. For those in the general population with long COVID symptoms, the role of specific nutrients has not yet been studied well enough to recommend any particular nutrient or dietary intervention as a treatment or adjunctive treatment. Clinical trials of single nutrients are currently being conducted, and future systematic reviews could focus on single nutrient or dietary interventions to identify their nuanced mechanisms of action. Further clinical studies incorporating complex nutritional interventions are also warranted to strengthen the evidence base for using nutrition as a useful adjunctive treatment for people living with long COVID.


Asunto(s)
COVID-19 , Desnutrición , Sarcopenia , Humanos , Síndrome Post Agudo de COVID-19 , Vitaminas/uso terapéutico , Desnutrición/prevención & control , Apoyo Nutricional , Glutatión , Antiinflamatorios , Inflamación
6.
Rheumatology (Oxford) ; 62(6): 2325-2329, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36651676

RESUMEN

OBJECTIVES: Nailfold capillaroscopy is key to timely diagnosis of SSc, but is often not used in rheumatology clinics because the images are difficult to interpret. We aimed to develop and validate a fully automated image analysis system to fill this gap. METHODS: We mimicked the image interpretation strategies of SSc experts, using deep learning networks to detect each capillary in the distal row of vessels and make morphological measurements. We combined measurements from multiple fingers to give a subject-level probability of SSc.We trained the system using high-resolution images from 111 subjects (group A) and tested on images from subjects not in the training set: 132 imaged at high-resolution (group B); 66 imaged with a low-cost digital microscope (group C). Roughly half of each group had confirmed SSc, and half were healthy controls or had primary RP ('normal'). We also estimated the performance of SSc experts. RESULTS: We compared automated SSc probabilities with the known clinical status of patients (SSc versus 'normal'), generating receiver operating characteristic curves (ROCs). For group B, the area under the ROC (AUC) was 97% (94-99%) [median (90% CI)], with equal sensitivity/specificity 91% (86-95%). For group C, the AUC was 95% (88-99%), with equal sensitivity/specificity 89% (82-95%). SSc expert consensus achieved sensitivity 82% and specificity 73%. CONCLUSION: Fully automated analysis using deep learning can achieve diagnostic performance at least as good as SSc experts, and is sufficiently robust to work with low-cost digital microscope images.


Asunto(s)
Aprendizaje Profundo , Esclerodermia Sistémica , Humanos , Uñas/diagnóstico por imagen , Uñas/irrigación sanguínea , Sensibilidad y Especificidad , Curva ROC , Capilares/diagnóstico por imagen , Angioscopía Microscópica/métodos
8.
Sci Rep ; 12(1): 20446, 2022 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-36443311

RESUMEN

Systemic sclerosis (SSc)-related digital ischaemia is a major cause of morbidity, resulting from a combination of microvascular and digital artery disease. Photoacoustic imaging offers a newly available, non-invasive method of imaging digital artery structure and oxygenation. The aim of this study was to establish whether photoacoustic imaging could detect and measure vasculopathy in digital arteries, including the level of oxygenation, in patients with SSc and healthy controls. 22 patients with SSc and 32 healthy controls (HC) underwent photoacoustic imaging of the fingers. Vascular volume and oxygenation were assessed across eight fingers at the middle phalanx. In addition, oxygenation change during finger occlusion was measured at the non-dominant ring finger and the vascular network was imaged along the length of one finger for qualitative assessment. There was no statistically significant difference in vascular volume between patients with SSc and HC (mean of eight fingers; SSc, median 118.6 IQR [95.0-130.5] vs. HC 115.6 [97.8-158.9]) mm3. However, baseline oxygenation (mean 8 fingers) was lower in SSc vs. HC (0.373 [0.361-0.381] vs. 0.381 [0.373-0.385] arbitrary sO2 units respectively; p = 0.03). Hyperaemic oxygenation response following occlusion release was significantly lower in SSc compared to HC (0.379 [0.376-0.381] vs. 0.382 [0.377-0.385]; p = 0.03). Whilst vascular volume was similar between groups, digital artery oxygenation was decreased in patients with SSc as compared to HC, indicative of functional deficit. Photoacoustic imaging offers an exciting new method to image the vascular network in patients with SSc and the possibility to capture oxygenation as a functional measure.


Asunto(s)
Técnicas Fotoacústicas , Esclerodermia Sistémica , Enfermedades Vasculares , Humanos , Esclerodermia Sistémica/diagnóstico por imagen , Diagnóstico por Imagen , Dedos/diagnóstico por imagen , Arterias/diagnóstico por imagen
9.
Rheumatology (Oxford) ; 62(1): 335-340, 2022 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-35640131

RESUMEN

OBJECTIVES: To identify barriers to the use of nailfold capillaroscopy as a diagnostic tool for patients presenting with Raynaud's phenomenon in UK rheumatology centres and to obtain rheumatologists' views on a proposed internet-based standardized system for clinical reporting of nailfold capillaroscopy images. METHODS: An online survey was developed using expert opinion from clinicians, scientists and health service researchers. The survey was piloted and sent to UK-based rheumatologists using established electronic mailing lists between October 2020 and March 2021. Survey data were analysed using descriptive statistics. RESULTS: A total of 104 rheumatologists representing rheumatology centres across the UK responded to the survey. Wide variations in terms of workloads and practices were described. Thirty-four (33%) respondents reported using nailfold capillaroscopy only at their own centre, 33 (32%) referred to other centres, 9 (9%) did both and 28 (27%) did not use capillaroscopy at all. Of the 43 respondents using capillaroscopy on site, 25 (58%) used either a dermatoscope or universal serial bus microscope and 9 (21%) used videocapillaroscopy. Among the 61 respondents not undertaking capillaroscopy on site, barriers included lack of equipment (85%), lack of experience in acquiring images (69%) and lack of expertise in interpreting images (67%). Sixty-six respondents (63%) expressed interest in an internet-based, standardized automated system for reporting images. CONCLUSION: Most UK rheumatologists currently do not perform nailfold capillaroscopy on site. An internet-based nailfold capillaroscopy system for use with low-cost microscopes as well as with videocapillaroscopy could help increase uptake of capillaroscopy and thereby facilitate early diagnosis of SSc across the UK.


Asunto(s)
Enfermedad de Raynaud , Esclerodermia Sistémica , Humanos , Angioscopía Microscópica/métodos , Reumatólogos , Enfermedad de Raynaud/diagnóstico , Encuestas y Cuestionarios , Reino Unido , Uñas/diagnóstico por imagen , Capilares
11.
Leukemia ; 36(3): 781-789, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34675373

RESUMEN

Children with B-cell non-Hodgkin lymphoma (B-NHL) have an excellent chance of survival, however, current clinical risk stratification places as many as half of patients in a high-risk group receiving very intensive chemo-immunotherapy. TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort and determined their impact on survival. TP53 abnormalities were present in 54.7% of cases and were independently associated with a significantly inferior survival compared to those without a TP53 abnormality (PFS 70.0% vs 100%, p < 0.001, OS 78.0% vs 100%, p = 0.002). Moreover, amongst patients clinically defined as high-risk (stage III with high LDH or stage IV), those without a TP53 abnormality have superior survival compared to those with TP53 abnormalities (PFS 100% vs 55.6%, p = 0.005, OS 100% vs 66.7%, p = 0.019). Biallelic TP53 abnormalities were either maintained from the presentation or acquired at progression in all paired diagnosis/progression Burkitt lymphoma cases. TP53 abnormalities thus define clinical risk groups within paediatric B-NHL and offer a novel molecular risk stratifier, allowing more personalised treatment protocols.


Asunto(s)
Linfoma de Células B/genética , Proteína p53 Supresora de Tumor/genética , Adolescente , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Dosificación de Gen , Sitios Genéticos , Humanos , Lactante , Linfoma de Células B/patología , Masculino , Mutación
13.
Epigenetics ; 16(7): 808-817, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32965161

RESUMEN

Systemic Sclerosis (SSc) is an autoimmune connective tissue disease that leads to skin and lung fibrosis. The Wnt pathway is clearly elevated in SSc and is pro-fibrotic via activation of canonical Wnt signalling. sFRP-1 is a Wnt antagonist that acts as a negative regulator of Wnt signalling. We sought to measure the levels of serum sFRP-1 in early diffuse SSc patients compared to healthy controls and if this is regulated by microRNA27a-3p. Ten early diffuse SSc patients and healthy controls sera were taken and sFRP-1 quantified by ELISA. Skin biopsies were also taken in five SSc patients and controls. Fibroblasts were quantified for microRNA27-3p expression by Taqman qRT-PCR with an internal microRNA to normalize. 3'UTR luciferase assays were performed to confirm direct targets of microRNA27a-3p with microRNA overexpression. Fibroblasts were transfected with microRNA27a mimics or scramble controls and using ELISA sFRP-1 was quantified. Furthermore, Collagen, Axin-2, TIMP-1 and MMP-1 were measured. Serum sFRP-1 was significantly reduced in early diffuse SSc patients. We identified microRNA27a-3p-3p as regulating sFRP-1 in dermal fibroblasts. We found significantly elevated microRNA27a-3p in isolated dermal fibroblasts from SSc patients. We confirmed that sFRP-1 is a direct target of microRNA27a-3p through cloning of the 3'UTR into a luciferase vector. ECM genes were also upregulated by microRNA27a-3p-3p and the matrix-degrading enzyme MMP-1 was suppressed. Serum sFRP-1 is reduced in diffuse SSc patients and is regulated by microRNA27a-3p and this is a direct regulation. Modulation of microRNA27a-3p levels could mediate fibrosis regression.


Asunto(s)
MicroARNs , Esclerodermia Sistémica , Proteínas de la Ataxia Telangiectasia Mutada , Metilación de ADN , Fibroblastos , Fibrosis , Humanos , MicroARNs/metabolismo , Esclerodermia Sistémica/genética , Piel/metabolismo , Piel/patología , Vía de Señalización Wnt
15.
Circ Genom Precis Med ; 13(5): 531-540, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32924542

RESUMEN

BACKGROUND: Ischemic stroke is a devastating complication affecting children with sickle cell anemia. Genetic factors are likely to be important in determining the risk of stroke but are poorly defined. METHODS: We have studied a cohort of 19 children who had an overt ischemic stroke before 4 years of age. We predicted genetic determinants of stroke would be more prominent in this group. We performed whole exome sequencing on this cohort and applied 2 hypotheses to our variant filtering. First, we looked for strong, potentially mono- or oligogenic variants for ischemic stroke, and second, we considered that more common polygenic variants will be enriched in our cohort. Candidate variants emerging from both strategies were validated in a cohort of 283 patients with sickle cell anemia and known pediatric cerebrovascular outcomes. We used principal component analysis in this cohort to control for relatedness and population substructure. RESULTS: Our primary finding was that the Apoliprotein E genotypes ε2/ε4 and ε4/ ε4, defined by the interplay of rs7412 and rs429358, were associated with increased stroke risk, with an odds ratio of 4.35 ([95% CI, 1.85-10.0] P=0.0011) for ischemic stroke in the validation cohort. We also found that rs2297518 in NOS (NO synthase) 2 (odds ratio, 2.25 [95% CI, 1.21-4.19]; P=0.014) and rs2230123 in signal transducer and activator of transcription (odds ratio, 2.60 [95% CI, 1.30-5.20]; P=0.009) both had increased odds ratios for ischemic stroke, although these two variants were below the threshold for statistical significance after correction for multiple testing. CONCLUSIONS: These data identify new loci for future functional investigations into cerebrovascular disease in sickle cell anemia. Based on African population reference allele frequencies, the Apoliprotein E genotypes would be present in about 10% of children with sickle cell anemia and represent a genetic risk factor that is potentially modifiable by both dietary and pharmaceutical manipulation of its dyslipidemic effects.


Asunto(s)
Anemia de Células Falciformes/genética , Apolipoproteínas E/genética , Accidente Cerebrovascular/genética , Anemia de Células Falciformes/diagnóstico , Receptor 1 de Quimiocinas CX3C/genética , Preescolar , Colágeno Tipo VII/genética , Frecuencia de los Genes , Genotipo , Humanos , Proteínas de la Membrana/genética , Herencia Multifactorial/genética , Proteínas del Tejido Nervioso/genética , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Subunidades de Proteína/genética , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico
17.
Sch Psychol ; 35(3): 179-192, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32406736

RESUMEN

Effective classroom management is critical for student and teacher success. Because teachers receive limited preservice preparation and in-service support in classroom management, educational leaders (e.g., school psychologists, behavior coaches, mentor teachers, and administrators) need efficient and effective tools to identify teachers' strengths and needs and to guide professional development. Current approaches to assess teachers' classroom management are either (a) simple and efficient, but have unknown psychometric properties, or (b) psychometrically sound, but resource intensive. Thus, a Classroom Management Observation Tool (CMOT) that is simple, efficient, and has promising psychometric properties would fill a critical need in the field. This article describes the initial development and validation of the CMOT-a four-item rating of teachers' active supervision, opportunities to respond, specific praise, and positive to corrective ratio-and presents promising evidence of content validity, factor structure, interrater reliability, construct validity, and generalizability. Further research is needed to develop this tool for screening, progress monitoring, and other assessment purposes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Asunto(s)
Evaluación del Rendimiento de Empleados/normas , Competencia Profesional/normas , Psicometría/normas , Maestros/normas , Instituciones Académicas/normas , Adulto , Humanos , Psicometría/instrumentación , Psicometría/métodos , Reproducibilidad de los Resultados
18.
Microvasc Res ; 130: 104006, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32320708

RESUMEN

OBJECTIVE: A key unanswered question in systemic sclerosis (SSc) is how microvascular abnormality and fibrosis inter-relate. Our aim was to use state-of-the-art non-invasive imaging methods to gain new insights into pathophysiology, comparing patients with different subtypes of SSc, including early dcSSc, not only to healthy controls but also to patients with causes of Raynaud's phenomenon not progressing to fibrosis. METHODS: Laser Doppler imaging, nailfold capillaroscopy, spectroscopy, and ultrasound measured (respectively) perfusion, microvascular structure, oxygenation/oxidative stress, and skin thickening in the hands of 265 subjects: 31 patients with primary Raynaud's phenomenon (PRP), 35 with undifferentiated connective tissue disease (UCTD), 93 with limited cutaneous SSc (lcSSc), 46 with diffuse cutaneous SSc (dcSSc, including 27 'early') and 60 healthy controls. RESULTS: Mean perfusion was reduced in SSc groups compared to controls (lcSSc 172 perfusion units [standard deviation 157], late-dcSSc 90 [145], early-dcSSc 68 [137] vs. controls 211 [146]; p = 0.0002) as was finger-oxygenation (lcSSc 12.1 [13.6] arbitrary units [AU], late-dcSSc 12.2 [8.4], early-dcSSc 11.1 [11.3] vs controls 14.9 [10.5]; p = 0.0049). Oxidative stress was increased at the hand-dorsum in SSc groups (p = 0.0007). Perfusion positively correlated with oxygenation (r = 0.23, p < 0.001), and capillary density negatively with skin thickness (r = -0.26, p < 0.001). CONCLUSION: Our findings lend support to the hypothesis that in SSc, particularly early dcSSc, (but not in PRP or UCTD), reduced perfusion (together with structural microvascular abnormality) associates with reduced oxygenation, with oxidative stress and with skin thickening/fibrosis, most likely driving a vicious cycle which ultimately results in irreversible tissue injury. Findings in skin may mirror alterations in internal organs.


Asunto(s)
Flujometría por Láser-Doppler , Angioscopía Microscópica , Microvasos/diagnóstico por imagen , Enfermedad de Raynaud/diagnóstico por imagen , Esclerodermia Difusa/diagnóstico por imagen , Esclerodermia Limitada/diagnóstico por imagen , Piel/irrigación sanguínea , Ultrasonografía , Adulto , Velocidad del Flujo Sanguíneo , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Microcirculación , Microvasos/fisiopatología , Persona de Mediana Edad , Estrés Oxidativo , Oxígeno/sangre , Valor Predictivo de las Pruebas , Enfermedad de Raynaud/sangre , Enfermedad de Raynaud/patología , Enfermedad de Raynaud/fisiopatología , Flujo Sanguíneo Regional , Esclerodermia Difusa/sangre , Esclerodermia Difusa/patología , Esclerodermia Difusa/fisiopatología , Esclerodermia Limitada/sangre , Esclerodermia Limitada/patología , Esclerodermia Limitada/fisiopatología , Piel/metabolismo , Piel/patología , Análisis Espectral
20.
Rheumatology (Oxford) ; 58(3): 527-535, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30462328

RESUMEN

OBJECTIVE: SSc is an autoimmune connective tissue disease that results in skin fibrosis and currently has no effective treatment. Epigenetic modifications have been described and these may be key in initiating and driving fibroblast activation. Among these epigenetic modifications methylation may be of central importance. The aim of this study was to examine the role of methyl cap binding protein-2 (MeCP2) in SSc fibrosis. METHODS: We used healthy and SSc dermal fibroblasts to examine the role of MeCP2, using both small interfering RNA silencing and lentiviral overexpression to determine its effects. We also examined the expression of MeCP2 in SSc fibroblasts by immunoblotting. miRNA132 was quantified by Taqman real time PCR. RESULTS: We demonstrated that TGF-ß1 induced the expression of MeCP2 in normal cells, and showed that SSc fibroblasts expressed high levels of MeCP2 under basal conditions. MeCP2 positively regulated the expression of extracellular matrix through epigenetic repression of the Wnt antagonist sFRP-1, leading to enhanced Wnt signalling. This mediated fibrosis through glycolysis, as the glycolysis inhibitor 2-deoxyglucose diminished the Wnt-mediated collagen expression. MiR132 expression was reduced in SSc fibroblasts. CONCLUSION: The results suggest that an epigenetic loop exists mediating fibrosis. Targeting of MeCP2, as a key epigenetic regulator, may be a promising therapeutic approach, as would targeting the metabolic reprogramming that occurs through aerobic glycolysis.


Asunto(s)
Fibroblastos/metabolismo , Proteína 2 de Unión a Metil-CpG/metabolismo , Esclerodermia Sistémica/metabolismo , Piel/metabolismo , Epigénesis Genética , Matriz Extracelular/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Células HEK293 , Humanos , Proteína 2 de Unión a Metil-CpG/genética , ARN Interferente Pequeño , Esclerodermia Sistémica/genética , Esclerodermia Sistémica/patología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Piel/efectos de los fármacos , Piel/patología , Factor de Crecimiento Transformador beta1/farmacología
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