89 research outputs found
Papel de las células madre de la médula ósea en hepatología: estudios in vivo e in vitro
El hígado es el único órgano capaz de desencadenar un proceso regenerativo tras sufrir un daño o lesión restableciendo así su funcionalidad tisular. La regeneración hepática es un proceso complejo en el que interaccionan todos los componentes celulares del hígado con distintos elementos reguladores permitiendo la activación de diversas cascadas de señalización intracelular que activan la división celular en el parénquima hepático.
En los últimos años, se ha postulado la posible participación de las células madre adultas de médula ósea (BM-SC) en la regeneración hepática tras una insuficiencia hepática. La bibliografía ha demostrado ampliamente la capacidad de diferenciación de las BM-SC hacia células semejantes a hepatocitos. Sin embargo, se desconoce cuáles son los mecanismos de señalización que podrían regular este proceso de diferenciación. La ruta Wnt/ß-catenina juega un papel fundamental en el destino final que alcanzan las BM-SC, y podría ser clave una inactivación de esta ruta para la obtener la diferenciación final a hepatocitos funcionales. Sin embargo, la translocación nuclear de ß-catenina ha sido también relacionada con el desarrollo de procesos tumorales como el carcinoma hepatocelular o el hepatoblastoma.
Pese al elevado número de publicaciones en torno al papel de las BM-SC durante la regeneración hepática aún es desconocido el grado de implicación de estas células con el proceso regenerativo en el hígado. Se ha postulado que inmediatamente después de producirse un daño en el parénquima hepático se desencadenaría diversos mecanismos de señalización que liberarían a las BM-SC desde su reservorio en la médula ósea (MO) hasta el torrente sanguíneo a través del cuál alcanzarían el hígado. Este proceso migratorio se conoce como ¿Mobilización celular¿ y se sabe que está estrictamente regulada por el eje SDF-1/CXCR-4. Pese a todo, se desconoce cuál podría ser la señal que dispare este proceso. Se ha propuesto a la resección hepática o la patología subyacente como elementos clave para activar los procesos de mobilización aunque en este sentido la bibliografía es contradictoria.
Por otro lado, en la actualidad han surgido numerosas estrategias para mejorar a través del uso de distintos tipos de células madre la enfermedad hepática. Estas células madre han sido infundidas en varios modelos experimentales de daño hepático. Los resultados obtenidos ponen de manifiesto que las BM-SC tras alojarse en el hígado podrían ser capaces de diferenciarse a hepatocitos funcionales. No obstante, existen indicios para pensar que el efecto de las BM-SC no es directo, sino través de mecanismos de señalización paracrinos. De hecho, recientemente se han conseguido restaurar la funcionalidad hepática tras la infusión de un concentrado de medio de cultivo de MSC, que es rico en factores secretados por esta población
Residual stresses in Al2O3-ZrO2 multilayered ceramics: nature, evaluation and influence on the structural integrity
[ES] El presente trabajo comprende el diseño y procesamiento por colaje de suspensiones de sistemas multicapa basados en
capas gruesas de alúmina y capas finas de alúmina-circona. Durante el enfriamiento desde la temperatura de sinterización
se generan tensiones residuales en las capas debido a la expansión asociada a la transformación martensítica de la circona.
En esta investigación se estudian los parámetros de procesamiento para la fabricación de estos sistemas laminados y se
caracterizan microestructuralmente las capas que lo componen. Como resultado se obtienen multicapas cerámicas con
diferente relación de espesores entre capas adyacentes utilizando como método de control las cinéticas de colaje de los
correspondientes monolíticos. Adicionalmente, se determinan analíticamente las tensiones residuales generadas en los
laminados por medio de las diferencias volumétricas determinadas en ensayos dilatométricos y del módulo elástico de cada
capa. Se encuentra que en las capas delgadas se desarrollan elevadas tensiones de compresión mientras que en las gruesas
se inducen tensiones residuales de tracción. El efecto de estas tensiones sobre la integridad mecánica del material se discute
en términos de las observaciones de fenómenos de fisuración intrínseca: tanto de grietas de borde o “edge cracks” en la
superficie libre de las capas delgadas como de fisuras túnel o “tunneling cracks” en las capas gruesas.[EN] This work studies the design and processing by slip casting of multilayered systems based on thick alumina and thin aluminazirconia
layers. During cooling from the sintering temperature residual stresses may arise due to expansion associated to
the martensitic transformation of the zirconia. In this investigation, the processing parameters involved in the fabrication of
theses layered systems are studied and the respective layers microstructurally characterized. As a result, several multilayered
ceramics in terms of thickness ratio between adjacent layers are obtained by means of the casting kinetics of the corresponding
monoliths. Additionally, the residual stresses generated in the laminates are analytically determined through the difference
in shrinkage assessed with dilatometric tests and the elastic modulus corresponding to each layer. It is found that in the thin
layers elevated residual compressive stresses are generated whilst in the thick ones tensile residual stresses are induced.
The effect of these stresses on the mechanical integrity of the material is discussed in terms of the observations of intrinsic
cracking phenomena: both edge cracks at the free surface of the thin layers and tunneling cracks in the thick layers.El presente trabajo ha sido financiado por el Ministerio de Ciencia y Tecnología (MCYT) en el marco del proyecto Nº MAT2002-00368, así como por el programa de la Comunidad Europea bajo el contrato HPRN-CT-2002-00203, [SICMAC].Peer reviewe
El juego tradicional: ¿puente entre culturas? De lo posible a la realidad
Los juegos tradicionales dentro de una sociedad cumplen una función de enculturación, conservan y transmiten los valores profundos de la cultura popular, proporcionan una actividad motriz acorde con las características de sus practicantes, propician y facilitan las relaciones sociales entre los miembros de una misma generación y entre los de diferentes generaciones, y ayudan a conservar tradiciones de transmisión oral y el patrimonio lúdico, siendo considerados elementos de la cultura. El artículo se centra en las percepciones que los docentes tienen acerca de del juego tradicional como puente entre culturas para abordar la diversidad cultural existente en las aulas. Es por ello que el artículo se subtitula ‘de lo posible a la realidad’. Se abordará desde una investigación realizada a partir de tres grupos de discusión con maestros de entornos urbanos, de la periferia y rurales respectivamente, llevada a cabo en Granada con docentes de centros públicos y privados, y con contextos diferentes (marginales y normalizados). Se concluye con que existe un sentimiento de falta de preparación para abordar el tratamiento de la diversidad cultural y que en general hay una falta de sensibilidad hacia la pérdida de tradiciones de transmisión oral y vivencial ya que si bien se plantea con insistencia que hay que recuperar los juegos tradicionales, no hay ninguna alusión a los aspectos culturales que conllevan los mismo
Procaine Inhibits Osteo/Odontogenesis through Wnt/β-Catenin Inactivation
Introduction
Periodontitis is a complex pathology characterized by the loss of alveolar bone. The causes
and the mechanisms that promote this bone resorption still remain unknown. The knowledge
of the critical regulators involved in the alteration of alveolar bone homeostasis is of
great importance for developing molecular therapies. Procaine is an anesthetic drug with
demethylant properties, mainly used by dentists in oral surgeries. The inhibitor role of Wnt
signaling of procaine was described in vitro in colon cancer cells.
Methods
In this work we evaluated the role of procaine (1 uM) in osteo/odontogenesis of rat bone
marrow mesenchymal stem cells. Similarly, the mechanisms whereby procaine achieves
these effects were also studied.
Results
Procaine administration led to a drastic decrease of calcium content, alkaline phosphatase
activity, alizarin red staining and an increase in the expression of Matrix Gla Protein. With
respect to osteo/odontogenic markers, procaine decreased early and mature osteo/odontogenic
markers. In parallel, procaine inhibited canonical Wnt/β-catenin pathway, observing a
loss of nuclear β-catenin, a decrease in Lrp5 and Frizzled 3, a significant increase of sclerostin
and Gsk3β and an increase of phosphorylated β-catenin. The combination of osteo/
odontogenic stimuli and Lithium Chloride decreased mRNA expression of Gsk3β, recovered
by Procaine. Furthermore it was proved that Procaine alone dose dependently
increases the expression of Gsk3β and β-catenin phosphorylation. These effects of procaine
were also observed on mature osteoblast. Interestingly, at this concentration of procaine
no demethylant effects were observed.
PLO
Pathogenic pathways and therapeutic approaches targeting inflammation in diabetic nephropathy
Diabetic nephropathy (DN) is associated with an increased morbidity and mortality, resulting in elevated cost for public health systems. DN is the main cause of chronic kidney disease (CKD) and its incidence increases the number of patients that develop the end-stage renal disease (ESRD). There are growing epidemiological and preclinical evidence about the close relationship between inflammatory response and the occurrence and progression of DN. Several antiinflammatory strategies targeting specific inflammatory mediators (cell adhesion molecules, chemokines and cytokines) and intracellular signaling pathways have shown beneficial effects in experimental models of DN, decreasing proteinuria and renal lesions. A number of inflammatory molecules have been shown useful to identify diabetic patients at high risk of developing renal complications. In this review, we focus on the key role of inflammation in the genesis and progression of DN, with a special interest in effector molecules and activated intracellular pathways leading to renal damage, as well as a comprehensive update of new therapeutic strategies targeting inflammation to prevent and/or retard renal injury.The authors work has been supported by grants from Instituto de Salud Carlos III (ISCIII, FIS-FEDER PI17/00130, PI17/01495, PI19/00588, ERA-PerMed-JTC2018-PERSTIGAN AC18/00071), Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) and Cardiovascular (CIBERCV), Fondecyt
Project (No. 1160465), Spanish Ministry of Science and Innovation (RTI2018-098788-B-100, DTS17/00203, DTS19/00093, RYC-2017-22369), and Spanish Societies of Cardiology (SEC), Nephrology (SEN) and Atherosclerosis (SEA). The “PFIS” and “Sara Borrell” training program of the ISCIII supported the salary of MGH (FI18/00310),
SR-M (CD19/00021) and CH-B (CP16/00017). Córdoba University supported the salary of C.G.C
Nuclear Translocation of b-Catenin during Mesenchymal Stem Cells Differentiation into Hepatocytes Is Associated with a Tumoral Phenotype
Wnt/b-catenin pathway controls biochemical processes related to cell differentiation. In committed cells the alteration of
this pathway has been associated with tumors as hepatocellular carcinoma or hepatoblastoma. The present study evaluated
the role of Wnt/b-catenin activation during human mesenchymal stem cells differentiation into hepatocytes. The
differentiation to hepatocytes was achieved by the addition of two different conditioned media. In one of them, b-catenin
nuclear translocation, up-regulation of genes related to the Wnt/b-catenin pathway, such as Lrp5 and Fzd3, as well as the
oncogenes c-myc and p53 were observed. While in the other protocol there was a Wnt/b-catenin inactivation. Hepatocytes
with nuclear translocation of b-catenin also had abnormal cellular proliferation, and expressed membrane proteins involved
in hepatocellular carcinoma, metastatic behavior and cancer stem cells. Further, these cells had also increased auto-renewal
capability as shown in spheroids formation assay. Comparison of both differentiation protocols by 2D-DIGE proteomic
analysis revealed differential expression of 11 proteins with altered expression in hepatocellular carcinoma. Cathepsin B and
D, adenine phosphoribosyltransferase, triosephosphate isomerase, inorganic pyrophosphatase, peptidyl-prolyl cis-trans
isomerase A or lactate dehydrogenase b-chain were up-regulated only with the protocol associated with Wnt signaling
activation while other proteins involved in tumor suppression, such as transgelin or tropomyosin b-chain were downregulated
in this protocol. In conclusion, our results suggest that activation of the Wnt/b-catenin pathway during human
mesenchymal stem cells differentiation into hepatocytes is associated with a tumoral phenotyp
In Urinary Incontinence Rehabilitation treated there is clinical improvement and decrease in electromyographic values with age
Introduction. The pelvic floor (SP) is formed by a set of muscular structures, which together with the fascias and ligaments make up the pelvic diaphragm. The function of the SP is the support of the pelvic organs and maintain a correct position of these, influencing urination, intercourse, childbirth and defecation. A weakness or injury of these structures predisposes to the appearance of a symptomatology that can occur in isolation or in combination, one of the main problems being UI urinary incontinence and pelvic organ prolapse POP(1). It is estimated a prevalence of UI in adults between 15 and 30%, presenting in all ages, detecting a progressive increase as age advances and POP in 50% of women who have had at least one vaginal delivery.(2-4)
Objectives. Evaluate both clinically and electromyographically a group of women diagnosed with UI and / or POP, after performing a rehabilitative treatment and one year of follow-up.
Material and methods. This is a longitudinal, analytical observational study of a prospective cohort type, where women aged between 18 and 85 years were evaluated in a period of time between January 2008 and January 2012. The variables used In the present study, they differed in clinical and electromyographic variables. For the evaluation of the MSP an intravaginal surface EMG was performed, which consisted in a quantitative muscular diagnostic evaluation and in which some known muscle parameters were obtained. A rehabilitation treatment protocol was designed, following the guidelines established according to scientific evidence.
Results. In the present study a total of 241 women were included, whose average age was 50.4 years (SD = 12.3), the mean BMI was 27.7 kg / m2, the average duration of symptoms was 6.9 years (SD = 8.9). 88% of women consulted by IU and 29% by POP. The most frequent diagnosis was that of IUM in 118 women (49.0%), followed by SUI in 65 women (27.0%). 49.4% were menopausal, 85.1% had vaginal delivery, only 2.9% were nulliparous. The mean number of deliveries was 2.4 (SD = 1.1) and in 89% of the cases they suffered episiotomy. 92.1% of the women in the sample had urine leaks, 96.4% of them related to the effort. Of the total sample, 189 patients (78.4%) performed treatment in the SP Unit. The average number of sessions was 14.2 (SD = 7.8). At the end of the rehabilitation treatment, 92.3% of the patients reported finding themselves better, 42% of the women presented voiding urgencies, and 47.6% suffered from UUI. The analysis of repeated measures of the electromyographic variables before and after the rehabilitation treatment and during the year of follow-up, statistically significant increases were observed in the maximum values of the phasic contractions, the average values of the tonic contractions, the duration of the tonic contraction selected and the total power of the ttonic contraction. When the means of the maximum values of the phasic contractions were compared, the maximum values of the tonic contractions and the average values of the tonic contractions with the degrees of the modified Oxford scale obtained statistically significant results.
Conclusions. The rehabilitation treatment has achieved an improvement perceived by the patients in 92% of them after finishing the treatment and an improvement in 75% at one year of follow-up. There is a decrease in the maximum values recorded in the EMG by age, decade by decade, experiencing a significant drop in the group of women ≥70 years
Toll-like receptors in acute kidney injury
Acute kidney injury (AKI) is an important health problem, affecting 13.3 million individuals/year. It is associated with increased mortality, mainly in low- and middle-income countries, where renal replacement therapy is limited. Moreover, survivors show adverse long-term outcomes, including increased risk of developing recurrent AKI bouts, cardiovascular events, and chronic kidney disease. However, there are no specific treatments to decrease the adverse consequences of AKI. Epidemiological and preclinical studies show the pathological role of inflammation in AKI, not only at the acute phase but also in the progression to chronic kidney disease. Toll-like receptors (TLRs) are key regulators of the inflammatory response and have been associated to many cellular processes activated during AKI. For that reason, a number of anti-inflammatory agents targeting TLRs have been analyzed in preclinical studies to decrease renal damage during AKI. In this review, we updated recent knowledge about the role of TLRs, mainly TLR4, in the initiation and development of AKI as well as novel compounds targeting these molecules to diminish kidney injury associated to this pathological conditionThe authors work has been supported by grants from Instituto de Salud Carlos III (ISCIII,
FIS-FEDER PI17/00130, PI17/01495, PI20/00375, PI20/00487), Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) and Cardiovascular (CIBERCV), Spanish Ministry of Science and Innovation (RTI2018-099114-B-100, RTI2018-098788-B-100, DTS19/00093, RYC-2017-22369), and Spanish Societies of Cardiology (SEC), Nephrology (SEN) and Atherosclerosis
(SEA). The “PFIS” and “Sara Borrell” training program of the ISCIII supported the salary of MGH (FI18/00310), SR-M (CD19/00021) and CH-B (CP16/00017). Córdoba University supported the salary of C.G.C
In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/β-catenin activation
The present study investigates the differential effect of two vitamin D receptor agonists, calcitriol and paricalcitol, on human aortic smooth muscle cells calcification in vitro. Human vascular smooth muscle cells were incubated in a high phosphate (HP) medium alone or supplemented with either calcitriol 10−8M (HP + CTR) or paricalcitol 3·10−8 M (HP + PC). HP medium induced calcification, which was associated with the upregulation of mRNA expression of osteogenic factors such as bone morphogenetic protein 2 (BMP2), Runx2/Cbfa1, Msx2, and osteocalcin. In these cells, activation of Wnt/β-catenin signaling was evidenced by the translocation of β-catenin into the nucleus and the increase in the expression of direct target genes as cyclin D1, axin 2, and VCAN/versican. Addition of calcitriol to HP medium (HP + CTR) further increased calcification and also enhanced the expression of osteogenic factors together with a significant elevation of nuclear β-catenin levels and the expression of cyclin D1, axin 2, and VCAN. By contrast, the addition of paricalcitol (HP + PC) not only reduced calcification but also downregulated the expression of BMP2 and other osteoblastic phenotype markers as well as the levels of nuclear β-catenin and the expression of its target genes. The role of Wnt/β-catenin on phosphate- and calcitriol-induced calcification was further demonstrated by the inhibition of calcification after addition of Dickkopf-related protein 1 (DKK-1), a specific natural antagonist of the Wnt/β-catenin signaling pathway. In conclusion, the differential effect of calcitriol and paricalcitol on vascular calcification appears to be mediated by a distinct regulation of the BMP and Wnt/β-catenin signaling pathways
Protective role of nrf2 in renal disease
Chronic kidney disease (CKD) is one of the fastest-growing causes of death and is predicted to become by 2040 the fifth global cause of death. CKD is characterized by increased oxidative stress and chronic inflammation. However, therapies to slow or prevent CKD progression remain an unmet need. Nrf2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that plays a key role in protection against oxidative stress and regulation of the inflammatory response. Consequently, the use of compounds targeting Nrf2 has generated growing interest for nephrologists. Pre-clinical and clinical studies have demonstrated that Nrf2-inducing strategies prevent CKD progression and protect from acute kidney injury (AKI). In this article, we review current knowledge on the protective mechanisms mediated by Nrf2 against kidney injury, novel therapeutic strategies to induce Nrf2 activation, and the status of ongoing clinical trials targeting Nrf2 in renal diseasesThe authors’work has been supported by grants FIS/Fondos FEDER (PI17/00130, PI17/00257,
PI17/01495, PI18/01386, PI19/00815, PI20/00375, PI20/00487 ISCIII-RETIC REDinREN RD016/0009),
Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686
CIFRA2-CM. Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders
(CIBERDEM) and Cardiovascular (CIBERCV), Spanish Ministry of Science and Innovation
(RTI2018-098788-B-100, DTS17/00203, DTS19/00093, RYC-2017-22369, FJC2019-042028), The “PFIS”
and “Sara Borrell” training program of the ISCIII supported the salary of MGH (FI18/00310), SR-M
(CD19/00021), and CH-B (CP16/00017). Spanish Ministerio de Ciencia, Innovación y Universidades
(MICIU) grant RTI2018-100695-B-I00, Junta de Andalucía grants P18-RT-4264, 1263735-R and BIO-276,
the FEDER Funding Program from the European Union, and Universidad de Córdoba (to J.M.V.
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