18 research outputs found
Autologous Platelet-Rich Plasma in the Treatment of Perianal Fistula in Crohnâs Disease
[Aim] To assess clinical healing in patients with perianal Crohnâs disease with local intrafistular injection of autologous platelet-rich plasma.[Method] The pilot study was conducted at a single centre between January 2013 and December 2015. Autologous platelet-rich plasma was prepared in platelet-rich and platelet-poor fractions for local intrafistular injection in patients with proven, established perianal Crohnâs disease. Patients were permitted biological therapies, and the Perianal Crohnâs Disease Activity Index was recorded. Patients were followed for 48 weeks for clinical signs of healing (complete, partial or non-healing), monitoring fistula drainage, closure and epithelialization.[Results] The study included 29 patients (19 males; mean age 38 ± 12.8 years) with four exclusions in the operating room because surgery was not indicated and four lost to follow-up. Five adverse events were recorded, with two requiring the drainage of abscess collections. Of the 21 patients assessable at 24 weeks, there was complete healing, partial healing and non-healing in 7 (33.3%), 8 (38.1%) and 6 (28.6%) patients, respectively. By 48 weeks, there was complete healing, partial healing and non-healing in 6 (40%), 6 (40%) and 3 (20%) patients, respectively, with a reduction in the number of visible external fistula openings at both time points (P = 0.021). By the end of the study, there was a higher trend of healing if biological therapies were continued (85.7% with biologics vs. 75% without, P = 0.527), but there were no statistically significant differences and no differences in the Perianal Crohnâs Disease Activity Index.[Conclusion]Autologous platelet-rich plasma is safe in patients with perianal Crohnâs disease, with an acceptable healing rate over a medium-term follow-up, particularly if biological therapies are used concomitantly
Molecular Pathways Leading to Induction of Cell Death and Anti-Proliferative Properties by Tacrolimus and mTOR Inhibitors in Liver Cancer Cells
Background/Aims:
Orthotopic liver transplantation (OLT) is the recommended treatment for
patients at early stages of hepatocarcinoma (HCC) with portal hypertension and/or increased
bilirubinemia, but without vascular-associated diseases. Tumor recurrence, which is the
main drawback for the survival of patients submitted to OLT for HCC, has been related to
tumor-related variables and the immunosuppressive therapies. We have previously shown
that Tacrolimus (FK506) exerts a more potent pro-apoptotic and anti-proliferative effects
than the mammalian target of rapamycin (mTOR) inhibitors (Sirolimus and Everolimus) in
liver cancer cells. This study identified the role of the immunosuppressant partners such as
FK506-binding proteins (FKBPs) in the induction of cell death and arrest of cell proliferation
by immunosuppressants in two representative liver cancer cells.
Methods:
The regulation
of endoplasmic reticulum (ER) stress, apoptosis/autophagy, cell proliferation, and FKBPs
expression was determined in Tacrolimus-, Sirolimus- and Everolimus-treated primary human
hepatocytes, and hepatoma HepG2 and Huh7 cell lines. The functional repercussion of FKBPs
on cell death and proliferation was also addressed using the siRNA technology. The assessed antitumoral properties of the immunosuppressants were associated to microRNAs (miRNAs)
pattern.
Results:
The enhanced pro-apoptotic and anti-proliferative properties of Tacrolimus
versus
mTOR inhibitors were associated with increased protein kinase RNA-like
endoplasmic
reticulum
kinase (PERK)-related ER stress,
Ser15
P-p53/p53 ratio and p21 protein expression that
may counterbalance the risk of proliferative upregulation caused by enhanced
Thr172
P-Cdk4/
Cdk4 activation in liver cancer cells. The inhibition of the mTOR pathway by Sirolimus and
Everolimus was related to an induction of autophagy; and at a high dose, these drugs impaired
translation likely at a very early step of the elongation phase. Tacrolimus and mTOR inhibitors
increased the protein expression of FKBP12 and FKBP51 that appeared to play pro-survival role.
Interestingly, the administration of immunosuppressants yields a specific pattern of miRNAs.
Tacrolimus and mTOR inhibitors decreased miR-92a-1-5p, miR-197-3p, miR-483-3p and miR-
720, and increased miR-22-3p, miR-376a-3p, miR-663b, miR-886-5p, miR-1300 and miR-1303
expressions in HepG2 cells.
Conclusion:
The more potent pro-apoptotic and anti-proliferative
properties of Tacrolimus
versus
mTOR inhibitors were associated with an increased activation
of PERK and p53 signaling, and p21 protein expression. FKBP12 and FKBP51 appeared to be
the most relevant partners of Tacrolimus and mTOR inhibitors exerting a pro-survival effect in
HepG2 cells. The observed effects of immunosuppressants were related to a specific miRNA
signature in liver cancer cellsEspaña Ministry of Economy and Competitiveness (MINECO) cofinanced by the ERDF (BFU2016-75352-P AEI/FEDER, EU
An actionable guide to creating Educational Escape Rooms: handbook
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En praktisk guide til brugen af didaktiske gÄderum undervisning: hÄndbog
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An Actionable Guide to Creating Educational Escape Rooms: Handbook
The UNLOCK project - Creativity through game-based learning at higher education â aims to equip HEIs to design, set and facilitate escape room games in their learning experiences, to foster the creativity and other entrepreneurial skills of HEIâs students. The UNLOCK project will provide the context, process and tools based on a new and innovative learning approach that stimulates entrepreneurial skills in both students and educators, aiming at strengthening employability, creativity and new professional paths
Um guia pråtico para a criação de Escape Rooms Educacionais
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Praktischer Leitfaden fĂŒr die Gestaltung von PĂ€dagogischer Escape Rooms
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GuĂa prĂĄctica para crear Escape Rooms Educativos: manual
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Praktinis EdukaciniĆł PabÄgimo KambariĆł KĆ«rimo Vadovas
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