96 research outputs found
Electrospun nanofibrous meshes cultured with Wharton’s Jelly Stem Cell: an alternative for cartilage regeneration, without the need of growth factors
Many efforts are being directed worldwide to the treatment of OA-focal lesions.
The majority of those efforts comprise either the refinement of surgical
techniques or combinations of biomaterials with various autologous cells.
Herein, we tested electrospun polycaprolactone (PCL) nanofibrous meshes for
cartilage tissue engineering. For that, articular chondrocytes (hACs) isolated
from human osteoarthritic joints and Whartonâ s Jelly Stem Cells (hWJSCs) are
cultured on electrospun nanofiber meshes, without adding external growth
factors. We observed higher glycosaminoglycans production and higher overexpression
of cartilage-related genes from hWJSCs cultured with basal medium,
when compared to hACs isolated from osteoarthritic joints. Moreover, the
presence of sulfated proteoglycans and collagen type II is observed on both
types of cell cultures. We believe that this effect is due to either the electrospun
nanofibers topography or the intrinsic chondrogenic differentiation potential of
hWJSCs. Therefore, we propose the electrospun nanofibrous scaffolds in
combination with hWJSCs as a viable alternative to the commercial membranes
used in autologous chondrogenic regeneration approaches.The authors thank the Portuguese Foundation for Science and
Technology for the Post-Doc grant of Marta Alves da Silva (SFRH/BPD/73322/2010, financed by POPH QREN Tipologia 4.1 – Advanced Formation, co-financed by Fundo Social Europeu and MEC
national funds). This work was supported by the project SPARTAN (PTDC/CTM-BIO/4388/2014) FCT/MEC with PIDDAC funds. It was also partly supported by the POLARIS (FP7-REGPOT-2012-2013-1) and the
Project “New methodologies for the isolation and control of stem cells
differentiation using advanced culturing conditions and/or nanomaterials”
(RL2 SCN NORTE-01-0124-FEDER-000018), co-financed by
North Portugal Regional Operational Programme (ON.2 – O Novo
Norte), under the National Strategic Reference Framework (NSRF),
through the European Regional Development Fund (ERDF).info:eu-repo/semantics/publishedVersio
Differences in persistence, safety and efficacy of generic and original branded once weekly bisphosphonates in patients with postmenopausal osteoporosis: 1-year results of a retrospective patient chart review analysis
Correlation versus Causation? Pharmacovigilance of the Analgesic Flupirtine Exemplifies the Need for Refined Spontaneous ADR Reporting
Annually, adverse drug reactions result in more than 2,000,000 hospitalizations and rank among the top 10 causes of death in the United States. Consequently, there is a need to continuously monitor and to improve the safety assessment of marketed drugs. Nonetheless, pharmacovigilance practice frequently lacks causality assessment. Here, we report the case of flupirtine, a centrally acting non-opioid analgesic. We re-evaluated the plausibility and causality of 226 unselected, spontaneously reported hepatobiliary adverse drug reactions according to the adapted Bradford-Hill criteria, CIOMS score and WHO-UMC scales. Thorough re-evaluation showed that only about 20% of the reported cases were probable or likely for flupirtine treatment, suggesting an incidence of flupirtine-related liver injury of 1∶ 100,000 when estimated prescription data are considered, or 0.8 in 10,000 on the basis of all 226 reported adverse drug reactions. Neither daily or cumulative dose nor duration of treatment correlated with markers of liver injury. In the majority of cases (151/226), an average of 3 co-medications with drugs known for their liver liability was observed that may well be causative for adverse drug reactions, but were reported under a suspected flupirtine ADR. Our study highlights the need to improve the quality and standards of ADR reporting. This should be done with utmost care taking into account contributing factors such as concomitant medications including over-the-counter drugs, the medical history and current health conditions, in order to avoid unjustified flagging and drug warnings that may erroneously cause uncertainty among healthcare professionals and patients, and may eventually lead to unjustified safety signals of useful drugs with a reasonable risk to benefit ratio
Retinoic Acids Potentiate BMP9-Induced Osteogenic Differentiation of Mesenchymal Progenitor Cells
As one of the least studied bone morphogenetic proteins (BMPs), BMP9 is one of the most osteogenic BMPs. Retinoic acid (RA) signaling is known to play an important role in development, differentiation and bone metabolism. In this study, we investigate the effect of RA signaling on BMP9-induced osteogenic differentiation of mesenchymal progenitor cells (MPCs).Both primary MPCs and MPC line are used for BMP9 and RA stimulation. Recombinant adenoviruses are used to deliver BMP9, RARalpha and RXRalpha into MPCs. The in vitro osteogenic differentiation is monitored by determining the early and late osteogenic markers and matrix mineralization. Mouse perinatal limb explants and in vivo MPC implantation experiments are carried out to assess bone formation. We find that both 9CRA and ATRA effectively induce early osteogenic marker, such as alkaline phosphatase (ALP), and late osteogenic markers, such as osteopontin (OPN) and osteocalcin (OC). BMP9-induced osteogenic differentiation and mineralization is synergistically enhanced by 9CRA and ATRA in vitro. 9CRA and ATRA are shown to induce BMP9 expression and activate BMPR Smad-mediated transcription activity. Using mouse perinatal limb explants, we find that BMP9 and RAs act together to promote the expansion of hypertrophic chondrocyte zone at growth plate. Progenitor cell implantation studies reveal that co-expression of BMP9 and RXRalpha or RARalpha significantly increases trabecular bone and osteoid matrix formation.Our results strongly suggest that retinoid signaling may synergize with BMP9 activity in promoting osteogenic differentiation of MPCs. This knowledge should expand our understanding about how BMP9 cross-talks with other signaling pathways. Furthermore, a combination of BMP9 and retinoic acid (or its agonists) may be explored as effective bone regeneration therapeutics to treat large segmental bony defects, non-union fracture, and/or osteoporotic fracture
Hepatocyte-specific contrast agent-enhanced magnetic resonance cholangiography: perioperative evaluation of the biliary tree
Monitoring of liver function in a 73-year old patient undergoing ‘Associating Liver Partition and Portal vein ligation for Staged hepatectomy’: case report applying the novel liver maximum function capacity test
Selecting men for bone densitometry: performance of osteoporosis risk assessment tools in Portuguese men
Alkali Cation Effect on CO2 Electroreduction to CO: A Local Colligative Property
Converting carbon dioxide (CO2) into valuable products is one of the most important processes for a sustainable society. Especially, the electrochemical CO2 reduction reaction (CO2RR) offers an effective means, but its reaction mechanism is not yet fully understood. Here, we demonstrate that cation-coupled electron transfer (CCET) is a rate-determining step in the CO2RR to carbon
monoxide. The first-principles-based multiscale simulation identifies a single cation that coordinates a CO2− intermediate adsorbed on Ag electrode. The CCET is experimentally verified by a collapse of the CO2RR polarization curves upon correcting Nernstianly for a bulk cation concentration. As further confirmation, a kinetic study shows that the CO2RR obeys first-order kinetics on a local cation concentration. Finally, this work unveils that the cation effect on CO2RR originates from the local colligative property, and further highlights the importance of ion-pairing tendency for electrochemical interface design to achieve high-performance CO2 electrolysis
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