233 research outputs found
Efecto diferencial del calcitriol y del paricalcitol sobre el proceso de calcificación en células de músculo liso vascular. Mecanismos intracelulares implicados
La primera causa de muerte en pacientes con Enfermedad Renal Crónica
(ERC) es la enfermedad cardiovascular (ECV), siendo su índice al menos 20
veces más alto en pacientes en diálisis que en la población general. Los pacientes
con ERC sufren hiperfosfatemia y otras alteraciones del metabolismo mineral que
les conducen al desarrollo de Hiperparatiroidismo Secundario (HPT2o) y de
calcificaciones vasculares (CV); estas últimas contribuyen a la alta tasa de
morbilidad y mortalidad cardiovascular observada en estos pacientes. La CV es un
proceso activo que implica la transformación osteogénica de las células de
músculo liso vascular (CMLV), aunque los mecanismos celulares y moleculares
por los que ocurren no están completamente definidos. Se ha descrito que niveles
elevados de fosfato (PO) inducen la calcificación y la diferenciación de las
CMLV.
El calcitriol (CTR), molécula empleada en el tratamiento del HPT2o en las
últimas décadas, induce hipercalcemia y un aumento del producto calcio x
fósforo, favoreciendo el desarrollo de CV. Actualmente, se vienen usando
análogos de la vitamina D menos calcémicos como el paricalcitol (PC), que ha
resultado ser efectivo en el tratamiento del HPT2º sin inducir CV. No obstante, los
mecanismos moleculares que median el efecto diferencial del calcitriol y del
paricalcitol sobre las CV no están del todo claros. Uno de los objetivos de este
estudio es determinar si los tratamientos con calcitriol o con paricalcitol
modularán de manera desigual la calcificación, la transformación osteogénica y
las vías de señalización intracelular relacionadas con la CV de las CMLV
inducidas por niveles elevados de fosfato...Cardiovascular disease (CVD) is the main cause of death in patients with
chronic kidney disease (CKD), with a frequency 20 times higher than the
observed in the general population. CKD patients exhibit hyperphosphatemia and
other disorders of mineral metabolism that lead to the development of Secondary
Hyperparathyroidism (HPT2º) and vascular calcification (VC). Both of them
contribute to the high rate of cardiovascular morbidity and mortality observed in
uremic patients. CV is an active process involving osteogenic transformation of
vascular smooth muscle cells (VSMC), although the underlying cellular and
molecular mechanisms are not fully elucidated. It has been described that elevated
levels of phosphate (PO) induce calcification and differentiation of VSMCs.
Calcitriol (CTR), molecule which has been used for the treatment of
HPT2º during the last decades, has an effect producing hypercalcemia and
increasing the calcium x phosphorus product, as well as promoting the
development of VC. Currently, less calcemic vitamin D analogues are being used.
For instance, paricalcitol (PC) has been proved to be effective in controlling
HPT2º without inducing VC. Nevertheless, the molecular mechanisms mediating
the differential effect of CTR and PC are not entirely clear. One objective of this
study is to determine whether treatment with CTR of PC will modulate differently
calcification, osteogenic transformation and intracellular signaling pathways
associated with high phosphate-induced VC.
Furthermore, two of the main factors associated with the progression and
severity of CKD are chronic inflammation and oxidative stress (OS), which have
also been related to VC. However, it is unclear to what extent phosphate has a..
Balancing porosity and mechanical properties of titanium samples to favor cellular growth against bacteria
Two main problems limit the success of titanium implants: bacterial infection, which restricts their osseointegration capacity; and the stiffness mismatch between the implant and the host cortical bone, which promotes bone resorption and risk of fracture. Porosity incorporation may reduce this difference in stiffness but compromise biomechanical behavior. In this work, the relationship between the microstructure (content, size, and shape of pores) and the antibacterial and cellular behavior of samples fabricated by the space-holder technique (50 vol % NH4HCO3 and three ranges of particle sizes) is established. Results are discussed in terms of the best biomechanical properties and biofunctional activity balance (cell biocompatibility and antibacterial behavior). All substrates achieved suitable cell biocompatibility of premioblast and osteoblast in adhesion and proliferation processes. It is worth to highlighting that samples fabricated with the 100–200 μm space-holder present better mechanical behavior—in terms of stiffness, microhardness, and yield strength—which make them a very suitable material to replace cortical bone tissues. Those results exposed the relationship between the surface properties and the race of bacteria and mammalian cells for the surface with the aim to promote cellular growth over bacteria.University of Seville (Spain) VI Plan Propio de Investigación y Transferencia—US 2018, I.3A
The contribution of histone crotonylation to tissue health and disease: focus on kidney health
Acute kidney injury (AKI) and chronic kidney disease (CKD) are the most severe
consequences of kidney injury. They are interconnected syndromes as CKD
predisposes to AKI and AKI may accelerate CKD progression. Despite their growing
impact on the global burden of disease, there is no satisfactory treatment for AKI and
current therapeutic approaches to CKD remain suboptimal. Recent research has focused
on the therapeutic target potential of epigenetic regulation of gene expression, including
non-coding RNAs and the covalent modifications of histones and DNA. Indeed, several
drugs targeting histone modifications are in clinical use or undergoing clinical trials. Acyllysine
histone modifications (e.g. methylation, acetylation, and crotonylation) have
modulated experimental kidney injury. Most recently, increased histone lysine
crotonylation (Kcr) was observed during experimental AKI and could be reproduced in
cultured tubular cells exposed to inflammatory stress triggered by the cytokine TWEAK.
The degree of kidney histone crotonylation was modulated by crotonate availability and
crotonate supplementation protected from nephrotoxic AKI. We now review the functional
relevance of histone crotonylation in kidney disease and other pathophysiological
contexts, as well as the implications for the development of novel therapeutic
approaches. These studies provide insights into the overall role of histone crotonylation in health and diseaseSources of support: FIS/FEDER funds (PI15/00298, CP14/00133,
PI16/02057, PI16/01900, PI18/01386, PI19/00588, PI19/00815,
DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK
AC18/00064 and PERSTIGAN AC18/00071), ISCIII-RETIC
REDinREN RD016/0009), Sociedad Española de Nefrología,
FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-
3686 CIFRA2-CM. Salary support: ISCIII Miguel Servet and to
AS and MS-N, ISCIII Sara Borrell to JM-M and Comunidad de
Madrid (B2017/BMD-3686 CIFRA2-CM) to MF-B and DM-S
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
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
Evaluación del impacto del perfil del alumnado en la valoración de la actividad docente del profesorado
En este proyecto se analiza el perfil de los estudiantes de primer curso en tres Grados (Química, Biología y Óptica-Optometría) de las Facultades de Ciencias de la UCM, detectando las carencias que presentan los estudiantes en una materia básica como la Química. Se comparan los resultados con los obtenidos en el curso académico 2016-2017. Asimismo se analiza la relación del perfil del alumnado con la valoración de la actividad docente del profesorado que realizan los estudiantes dentro del programa DOCENTIA
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
Artificial Modifications of the Coast In Response to the \u3ci\u3eDeepwater Horizon\u3c/i\u3e Oil Spill: Quick Solutions or Long-Term Liabilities?
The Deepwater Horizon oil spill threatened many coastal ecosystems in the Gulf of Mexico during the spring and summer of 2010. Mitigation strategies included the construction of barrier sand berms, the restriction or blocking of inlets, and the diversion of freshwater from rivers to the coastal marshes and into the ocean, in order to flush away the oil, on the premise that these measures could reduce the quantity of oil reaching sensitive coastal environments such as wetlands or estuaries. These projects result in changes to the ecosystems that they were intended to protect. Long-term effects include alterations of the hydrological and ecological characteristics of estuaries, changes in sediment transport along the coastal barrier islands, the loss of sand resources, and adverse impacts to benthic and pelagic organisms. Although there are no easy solutions for minimizing the impacts of the Deepwater Horizon disaster on coastal ecosystems, we recommend that federal, state, and local agencies return to the strategic use of long-term restoration plans for this region
Engineering periodic dinuclear lanthanide-directed networks featuring tunable energy level alignment and magnetic anisotropy by metal exchange
The design of lanthanide multinuclear networks is an emerging field of research due to the potential of such materials for nanomagnetism, spintronics, and quantum information. Therefore, controlling their electronic and magnetic properties is of paramount importance to tailor the envisioned functionalities. In this work, a multidisciplinary study is presented combining scanning tunneling microscopy, scanning tunneling spectroscopy, X-ray absorption spectroscopy, X-ray linear dichroism, X-ray magnetic circular dichroism, density functional theory, and multiplet calculations, about the supramolecular assembly, electronic and magnetic properties of periodic dinuclear 2D networks based on lanthanide-pyridyl interactions on Au(111). Er- and Dy-directed assemblies feature identical structural architectures stabilized by metal–organic coordination. Notably, despite exhibiting the same +3 oxidation state, there is a shift of the energy level alignment of the unoccupied molecular orbitals between Er- and Dy-directed networks. In addition, there is a reorientation of the easy axis of magnetization and an increment of the magnetic anisotropy when the metallic center is changed from Er to Dy. Thus, the results show that it is feasible to tune the energy level alignment and magnetic anisotropy of a lanthanide-based metal-organic architecture by metal exchange, while preserving the network desig
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