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Abstract: In patients on oral anticoagulant (OAC) therapy undergoing percutaneous coronary intervention (PCI) with stent, international guidelines endorse the use of direct oral anticoagulants (DOAC) rather than vitamin K antagonists (VKA) and dual antithrombotic therapy (DAT) rather than triple antithrombotic therapy (TAT). The aim of this study was to evaluate contemporary real-world data on antithrombotic regimens and outcome in patients on OAC undergoing PCI with stent. Consecutive patients on OAC undergoing PCI were enrolled in the multicenter, prospective, observational PERSEO registry (NCT03392948). Primary end point was net adverse clinical events (NACE) with VKA versus DOAC, whereas a secondary prespecified end point was NACE with DAT versus TAT both at 1-year follow-up. From February 2018 to February 2022; in total, 1234 consecutive patients were included. The main indication for OAC was atrial fibrillation (86%), and the mean CHA 2 DS 2 VASc and HAS-BLED scores were 4 ± 2 and 3.6 ± 1, respectively. Of the 1228 patients discharged alive, 222 (18%) were on VKA and 1006 (82%) on DOAC ( P < 0.01). DAT was employed in 197 patients whereas TAT in 1028. At follow-up, NACE rate was significantly higher than VKA compared with DOAC (23% vs. 16%, P = 0.013) and confirmed after propensity score adjustment. TAT and DAT did not differ as regards NACE rate (17% vs. 19%, P = 0.864) although, compared with TAT, DAT was associated with less major bleedings (2% vs. 5%, P = 0.014), confirmed after propensity score adjustment. In conclusion, in patients on OAC undergoing PCI, DOAC, compared with VKA, was associated with a significantly lower occurrence of NACE and DAT reduced bleedings compared with TAT., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

"Desert hyacinths" are a remarkable group of parasitic plants belonging to genus Cistanche, including more than 20 accepted species typically occurring in deserts or coastal dunes parasitizing roots of shrubs. Several Cistanche species have long been a source of traditional herbal medicine or food, being C. deserticola and C. tubulosa the most used in China. This manuscript reports the isolation and identification of some phenylethanoid and iridoid glycosides, obtained from the hydroalcoholic extract of C. phelypaea collected in Spain. The present study aims to characterize the antioxidant activity of C. phelypaea metabolites in the light of their application in nutraceutical and cosmeceutical industries and the effect of acetoside, the most abundant metabolite in C. phelypaea extract, on human keratinocyte and pluripotent stem cell proliferation and differentiation. Our study demonstrated that acetoside, besides its strong antioxidant potential, can preserve the proliferative potential of human basal keratinocytes and the stemness of mesenchymal progenitors necessary for tissue morphogenesis and renewal. Therefore, acetoside can be of practical relevance for the clinical application of human stem cell cultures in tissue engineering and regenerative medicine., (© 2022 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.)

Aim: Percutaneous coronary intervention with stent implantation (PCI-S) in patients requiring chronic oral anticoagulant therapy (OAC) is associated with an increased risk of bleeding and ischemic complications. Different randomized studies showed a significant advantage of a double antithrombotic therapy and superiority of direct oral anticoagulant (DOAC) compared with warfarin, but real-world data are limited. Aim is to evaluate the antithrombotic management and clinical outcome of patients with an indication for OAC who undergo PCI-S in a 'real-world' setting., Methods: The multicentre prospective observational PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) Registry (ClinicalTrials.gov Identifier: NCT03392948) has been designed to enrol patients requiring OAC treated by PCI-S in 25 Italian centres. A target of at least 1080 patients will be followed for 1 year and data on thromboembolic and bleeding events and changes in antithrombotic therapy will be registered. The primary end point is a combined measure of efficacy and safety outcome (NACE), including major bleeding events and major adverse cardiac and cerebral events at 1-year follow-up in patients treated with DOAC (and dual or triple antiplatelet therapy) compared with the corresponding strategies with vitamin K antagonists. A secondary prespecified analysis has been defined to evaluate NACE in dual versus triple antithrombotic therapy after hospital discharge at 1-year follow-up., Conclusion: The PERSEO Registry will investigate in a 'real world' setting the safety and efficacy of DOAC versus warfarin and dual versus triple antithrombotic therapy in patients with indication for oral anticoagulant therapy who undergo PCI-S., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Embryonic stem cells (ESCs) present a characteristic pluripotency heterogeneity correspondent to specific metastates. We recently demonstrated that retinoic acid (RA) induces an increase in a specific 2C-like metastate marked by target genes specific to the two-cell embryo stage in preimplantation. Prame (Preferentially expressed antigen in melanoma) is one of the principal actors of the pluripotency stage with a specific role in RA responsiveness. Additionally, PRAME is overexpressed in a variety of cancers, but its molecular functions are poorly understood. To further investigate Prame's downstream targets, we used a chromatin immunoprecipitation sequencing (ChIP-seq) assay in RA-enriched 2C-like metastates and identified two specific target genes, Cdk8 and Cdkn2d , bound by Prame. These two targets, involved in cancer dedifferentiation and pluripotency, have been further validated in RA-resistant ESCs. Here, we observed for the first time that Prame controls the Cdk8 and Cdkn2d genes in ESCs after RA treatment, shedding light on the regulatory network behind the establishment of naïve pluripotency.

The identification of the molecular mechanisms controlling early cell fate decisions in mammals is of paramount importance as the ability to determine specific lineage differentiation represents a significant opportunity for new therapies. Pancreatic Progenitor Cells (PPCs) constitute a regenerative reserve essential for the maintenance and regeneration of the pancreas. Besides, PPCs represent an excellent model for understanding pathological pancreatic cellular remodeling. Given the lack of valid markers of early endoderm, the identification of new ones is of fundamental importance. Both products of the Ink4a / Arf locus, in addition to being critical cell-cycle regulators, appear to be involved in several disease pathologies. Moreover, the locus' expression is epigenetically regulated in ES reprogramming processes, thus constituting the ideal candidates to modulate PPCs homeostasis. In this study, starting from mouse embryonic stem cells (mESCs), we analyzed the early stages of pancreatic commitment. By inducing mESCs commitment to the pancreatic lineage, we observed that both products of the Cdkn2a locus, Ink4a and Arf , mark a naïve pancreatic cellular state that resembled PPC-like specification. Treatment with epi-drugs suggests a role for chromatin remodeling in the CDKN2a (Cycline Dependent Kinase Inhibitor 2A) locus regulation in line with previous observations in other cellular systems. Our data considerably improve the comprehension of pancreatic cellular ontogeny, which could be critical for implementing pluripotent stem cells programming and reprogramming toward pancreatic lineage commitment.

Obesity and associated metabolic disturbances, which have been increasing worldwide in recent years, are the consequences of unhealthy diets and physical inactivity and are the main factors underlying non-communicable diseases (NCD). These diseases are now responsible for about three out of five deaths worldwide, and it has been shown that they depend on mitochondrial dysfunction, systemic inflammation and oxidative stress. It was also demonstrated that several nutritional components modulating these processes are able to influence metabolic homeostasis and, consequently, to prevent or delay the onset of NCD. An interesting combination of nutraceutical substances, named DMG-gold, has been shown to promote metabolic and physical wellness. The aim of this research was to investigate the metabolic, inflammatory and oxidative pathways modulated by DMG-gold in an animal model with diet-induced obesity. Our data indicate that DMG-gold decreases the metabolic efficiency and inflammatory state and acts as an antioxidant and detoxifying agent, modulating mitochondrial functions. Therefore, DMG-gold is a promising candidate in the prevention/treatment of NCD.

Cultured mouse embryonic stem cells are a heterogeneous population with diverse differentiation potential. In particular, the subpopulation marked by Zscan4 expression has high stem cell potency and shares with 2 cell stage preimplantation embryos both genetic and epigenetic mechanisms that orchestrate zygotic genome activation. Although embryonic de novo genome activation is known to rely on metabolites, a more extensive metabolic characterization is missing. Here we analyze the Zscan4 + mouse stem cell metabolic phenotype associated with pluripotency maintenance and cell reprogramming. We show that Zscan4 + cells have an oxidative and adaptable metabolism, which, on one hand, fuels a high bioenergetic demand and, on the other hand, provides intermediate metabolites for epigenetic reprogramming. Our findings enhance our understanding of the metastable Zscan4 + stem cell state with potential applications in regenerative medicine., (© 2020 The Authors.)

The fungal pathways of melanin synthesis have so far been little considered as a source of bio-inspiration in the field of functional materials, despite the interesting properties exhibited by Ascomycetes melanins from 1,8-dihydroxynaphthalene (1,8-DHN), including the ability to shield organisms from ionizing radiation. Herein, the processing techniques and characterizations of mycomelanin thin films obtained from the solid state polymerization of 1,8-DHN is reported for the first time. Overall, the results highlighted the role of synthetic mycomelanin thin films as a prototype of next generation bioinspired interfaces featuring high structural regularity and ultrasmooth morphology, high robustness against peroxidative bleaching and adhesion under water conditions, good biocompatibility and unprecedented effects in inducing the spontaneous differentiation of embryonic stem cells prevalently towards the endodermal lineages in the absence of added factors. These data open up new avenues towards the applications of this biomaterial in the fields of tissue engineering and regenerative medicine.

Endoderm-derived organs as liver and pancreas are potential targets for regenerative therapies, and thus, there is great interest in understanding the pathways that regulate the induction and specification of this germ layer. Currently, the knowledge of molecular mechanisms that guide the in vivo endoderm specification is restricted by the lack of early endoderm specific markers. Nephrocan ( Nepn ) is a gene whose expression characterizes the early stages of murine endoderm specification (E7.5-11.5) and encodes a secreted N-glycosylated protein. In the present study, we report the identification of a new transcript variant that is generated through alternative splicing. The new variant was found to have differential and tissue specific expression in the adult mouse. In order to better understand Nepn role during endoderm specification, we generated Nepn knock-out (KO) mice. Nepn -/- mice were born at Mendelian ratios and displayed no evident phenotype compared to WT mice. In addition, we produced nullizygous mouse embryonic stem cell (mESC) line lacking Nepn by applying (CRISPR)/CRISPR-associated systems 9 (Cas9) and employed a differentiation protocol toward endoderm lineage. Our in vitro results revealed that Nepn loss affects the endoderm differentiation impairing the expression of posterior foregut-associated markers.

Pancreatic organogenesis is a multistep process that requires the cooperation of several signaling pathways. In this context, the role of pancreatic mesenchyme is important to define the epithelium development; nevertheless, the precise space-temporal signaling activation still needs to be clarified. This study reports a dissection of the pancreatic embryogenesis, highlighting the molecular network surrounding the epithelium-mesenchyme interaction. To investigate this crosstalk, pancreatic epithelium and surrounding mesenchyme, at embryonic day 10.5, were collected through laser capture microdissection (LCM) and characterized based on their global gene expression. We performed a bioinformatic analysis to hypothesize crosstalk interactions, validating the most promising genes and verifying the precise localization of their expression in the compartments, by RNA in situ hybridization (ISH). Our analyses pointed out also the c-Met gene, a very well-known factor involved in stimulating motility, morphogenesis, and organ regeneration. We also highlighted the potential crosstalk between Versican (Vcan) and Syndecan4 (Sdc4) since these genes are involved in pancreatic tissue repair, strengthening the concept that the same signaling pathways required during pancreatic embryogenesis are also involved in tissue repair. This finding leads to novel strategies for obtaining functional pancreatic stem cells for cell replacement therapies.

Despite the significant recent advances in clinical practice, gastric cancer (GC) represents a leading cause of cancer-related deaths in the world. In fact, occurrence of chemo-resistance still remains a daunting hindrance to effectiveness of the current approach to GC therapy. There is accumulating evidence that a plethora of cellular and molecular factors is implicated in drug-induced phenotypical switching of GC cells. Among them, epithelial-mesenchymal transition (EMT), autophagy, drug detoxification, DNA damage response and drug target alterations, have been reported as major determinants. Intriguingly, resistant GC phenotype may be the result of GC cell-induced tumor microenvironment (TME) remodeling, which is currently emerging as a key player in promoting drug resistance and overcoming cytotoxic effects of drugs. In this review, we discuss the possible mechanisms of drug resistance and their involvement in determining current GC therapies failure.

Background: The bioresorbable vascular scaffold (BVS) technology may be an appealing option in ST-segment elevation myocardial infarction (STEMI) patients. However, the available evidence on its use in this challenging subset is limited., Methods: Registro Absorb Italiano (RAI) is a multicenter, prospective registry that aims to assess BVS performance through a 5-year follow-up of all consecutive patients who undergone at least 1 successful BVS implantation. As a part of it, a subgroup analysis in STEMI patients was performed and the outcomes of this cohort compared to the remaining population (defined as "non-STEMI") are reported here., Results: Among the 1505 patients enrolled, 317 (21.1%) had STEMI on admission. Among those, 232 (73.2%) underwent primary percutaneous coronary intervention (PCI) within 12 h from symptom onset; 64 (20.2%) were late-comers (>12 h); 16 (5%) underwent PCI after successful thrombolysis while 5 (1.6%) underwent rescue-PCI. At a median follow-up time of 12 months (IQR 6-20 months) no differences were noticed between STEMI and "non-STEMI" groups in terms of device-oriented composite endpoint (4.1% vs. 5.6%; p = 0.3) and its singular components: ischemia-driven target lesion revascularization (3.2% vs. 3.6%; p = 0.7), target-vessel myocardial infarction (3.2% vs. 2.8%; p = 0.7) and cardiac death (0.6% vs. 0.6%; p = 0.9). The rate of definite/probable scaffold thrombosis (ScT) was numerically higher but not significant in the STEMI group (2.5% vs. 1.3%; p = 0.1)., Conclusions: BVS implantation in an unrestricted cohort of STEMI patients is associated with a numerically higher rate of ScT compared to the non-STEMI group. Further studies exploring the potential clinical impact of a pre-specified BVS implantation strategy in this high-risk clinical setting are needed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To compare clinical outcomes of patients treated with overlapping versus non-overlapping Absorb BVS., Background: Limited data are available on the clinical impact of stent overlap with the Absorb BVS bioresorbable stent., Methods: We compared outcomes of patients receiving overlapping or non-overlapping Absorb BVS in the multicenter prospective RAI Registry., Results: Out of 1,505 consecutive patients treated with Absorb BVS, 1,384 were eligible for this analysis. Of these, 377 (27%) were in the overlap group, and 1,007 (73%) in the non-overlap group. The most frequent overlap configuration was the marker-to-marker type (48%), followed by marker-over-marker (46%) and marker-inside-marker (6%) types. Patients of the overlap group had higher prevalence of multivessel disease and higher SYNTAX score, and required more frequently the use of intravascular imaging. At a median follow-up of 368 days, no difference was observed between overlap and non-overlap groups in terms of a device-related composite endpoint (cardiac death, TV-MI, ID-TLR) (5.8% vs. 4.1%, P = 0.20) or of a patient-related composite endpoint (any death, any MI, any revascularization) (15.4% vs. 12.5%, P = 0.18). Cardiac death (1.0% vs. 1.3%, P = 0.54), MI (4.5% vs. 3.6%, P = 0.51), TVR (4.5% vs. 3.6%, P = 0.51) and stent thrombosis (1.1 vs. 1.5%, P = 1.00) were also comparable between groups. When assessing outcomes of the overlap population according to overlap configurations used, no difference was observed in terms of the device- or patient-related composite endpoints., Conclusions: Outcomes of patients with or without overlapping BVS were comparable at mid-term follow-up despite higher angiographic complexity of the overlap subset. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: The Absorb™ BVS is a bioresorbable, everolimus-eluting scaffold approved and marketed for coronary use. Published data on long-term results after treatment are limited to a small number of patients, most of them with elective PCI of simple lesions. The importance of scaffold resorption is variably appreciated among cardiologists, and indications for use from health technology assessment bodies or guidelines are missing. Instruments are needed to collect, share and assess the experience being accumulated with this new device in several centres., Methods/design: The BVS-RAI Registry is a spontaneous initiative of a group of Italian interventional cardiologists in cooperation with Centro di Ricerche Farmacologiche e Biomediche "Mario Negri" Institute, and is not recipient of funding or benefits originating from the BVS manufacturer. It is a prospective registry with 5-year follow-up of all consecutive patients who have undergone successful implantation of 1 or more coronary BVS following the indications, techniques and protocols used in each of the participating institutions. Outcome measures are BVS target lesion failure within one year and device-oriented major adverse cardiac events within 5years. The registry started in October 2012 and will extend enrolment throughout 2015, with the aim to include about 1000 patients. ClinicalTrials.gov identifier is CT02298413., Conclusions: The BVS-RAI Registry will contribute observational knowledge on the long-term safety and efficacy of the Absorb™ BVS as used in a number of Italian interventional centres in a broad spectrum of settings. Unrewarded and undirected consecutive patient enrolments are key-features of this observation, which is therefore likely to reflect common clinical practice in those centres., (Copyright © 2015 Elsevier Inc. All rights reserved.)

PAX8 is a transcription factor essential for thyroid gland development, as well as for the maintenance of the thyroid differentiated state in the adult. In particular, PAX8 has been comprehensively shown to regulate genes that are considered markers of thyroid differentiation. However, a better knowledge of genes transcriptionally regulated by PAX8 is desirable to clarify its role in endocrine syndromes and cancer susceptibility. In order to further investigate PAX8 downstream targets, we recently performed a genome-wide expression analysis following PAX8 knockdown in FRTL-5 thyroid cells and Neuropilin-2 was identified as a potential transcriptional target of PAX8. In this study, we determined the role of the transcription factor PAX8 in the regulation of Neuropilin-2 expression. Indeed, in thyroid cells PAX8 directly binds the Neuropilin-2 promoter leading to its transcriptional repression. Interestingly, we observed an inverse correlation between the expression of PAX8 and Neuropilin-2 in thyroid carcinoma tissues and cell lines compared to non-tumor counterparts, suggesting a critical role of PAX8 in regulating Neuropilin-2 expression in vivo. Notably, ectopic overexpression of PAX8 in FB-2 thyroid cancer cells promotes Neuropilin-2 downregulation producing a significant reduction in cell proliferation, migration ability, and invasion activity and reverting the cell phenotype from mesenchymal to a more epithelial one. These findings uncover the novel interplay between PAX8 and Neuropilin-2, which is likely to be important in the pathogenesis of thyroid diseases.

Background: The transcription factor Pax8 is expressed during thyroid development and is involved in the morphogenesis of the thyroid gland and maintenance of the differentiated phenotype. In particular, Pax8 has been shown to regulate genes that are considered markers of thyroid differentiation. Recently, the analysis of the gene expression profile of FRTL-5 differentiated thyroid cells after the silencing of Pax8 identified Wnt4 as a novel target. Like the other members of the Wnt family, Wnt4 has been implicated in several developmental processes including regulation of cell fate and patterning during embryogenesis. To date, the only evidence on Wnt4 in thyroid concerns its down-regulation necessary for the progression of thyroid epithelial tumors., Results: Here we demonstrate that Pax8 is involved in the transcriptional modulation of Wnt4 gene expression directly binding to its 5'-flanking region, and that Wnt4 expression in FRTL-5 cells is TSH-dependent. Interestingly, we also show that in thyroid cells a reduced expression of Wnt4 correlates with the alteration of the epithelial phenotype and that the overexpression of Wnt4 in thyroid cancer cells is able to inhibit cellular migration., Conclusions: We have identified and characterized a functional Pax8 binding site in the 5'-flanking region of the Wnt4 gene and we show that Pax8 modulates the expression of Wnt4 in thyroid cells. Taken together, our results suggest that in thyroid cells Wnt4 expression correlates with the integrity of the epithelial phenotype and is reduced when this integrity is perturbed. In the end, we would like to suggest that the overexpression of Wnt4 in thyroid cancer cells is able to revert the mesenchymal phenotype.

Background: PAX8 is a member of the paired box (Pax) multigene family of transcription factors, which are involved in the developmental and tissue-specific control of the expression of several genes in both vertebrates and invertebrates. Previously, several studies reported that PAX8 is expressed at high levels in specific types of tumors. In particular, PAX8 has been recently reported to be conspicuously expressed in human ovarian cancer, but the functional role of PAX8 in the carcinogenesis of this type of tumor has not been addressed. In this study, we investigated the contribution of PAX8 in ovarian cancer progression., Methods: Stable PAX8 depleted ovarian cancer cells were generated using short hairpin RNA (shRNA) constructs. PAX8 mRNA and protein were detected by RT-PCR, immunoblot and immunofluorescence. Cell proliferation, motility and invasion potential of PAX8 silenced cells were analyzed by means of growth curves, wound healing and Matrigel assays. In addition, PAX8 knockdown and control cells were injected into nude mice for xenograft tumorigenicity assays. Finally, qPCR was used to detect the expression levels of EMT markers in PAX8-overexpressing and control cells., Results: Here, we show that PAX8 plays a critical role in the migration, invasion and tumorigenic ability of ovarian cancer cells. Our results show that RNA interference-mediated knockdown of PAX8 expression in SKOV-3 ovarian cancer cells produces a significant reduction of cell proliferation, migration ability and invasion activity compared with control parental SKOV-3 cells. Moreover, PAX8 silencing strongly suppresses anchorage-independent growth in vitro. Notably, tumorigenesis in vivo in a nude mouse xenograft model is also significantly inhibited., Conclusions: Overall, our results indicate that PAX8 plays an important role in the tumorigenic phenotype of ovarian cancer cells and identifies PAX8 as a potential new target for the treatment of ovarian cancer.

Background: The role of intraaortic balloon pump (IABP) during percutaneous coronary intervention (PCI) in high-risk acute patients remains debated. Device-related complications and the more complex patient management could explain such lack of clinical benefit. We aimed to assess the impact of transradial versus transfemoral access for PCI requiring IABP support on vascular complications and clinical outcome., Methods: We retrospectively analyzed 321 consecutive patients receiving IABP support during transfemoral (n = 209) or transradial (n = 112) PCI. Thirty-day net adverse clinical events (NACEs) (composite of postprocedural bleeding, cardiac death, myocardial infarction, target lesion revascularization, and stroke) were the primary end point, with access-related bleeding and hospital stay as secondary end points., Results: Cardiogenic shock and hemodynamic instability were the most common indications for IABP support. Cumulative 30-day NACE rate was 50.2%, whereas an access site-related bleeding occurred in 14.3%. Patients undergoing transfemoral PCI had a higher unadjusted rate of NACEs when compared with the transradial group (57.4% vs 36.6%, P < .01), mainly due more access-related bleedings (18.7% vs 6.3%, P < .01). Such increased risk of NACEs was confirmed after propensity score adjustment (hazard ratio 0.57 [0.4-0.9], P = .007), whereas hospital stay appeared comparable in the 2 groups., Conclusions: In this observational registry, high-risk patients undergoing PCI and requiring IABP support appeared to have fewer NACEs if transradial access was used instead of transfemoral, mainly due to fewer access-related bleedings. Given the inherent limitations of this retrospective work, including the inability to adjust for unknown confounders, further controlled studies are warranted to confirm or refute these findings., (© 2013.)

Objectives: To evaluate the efficacy of the new Cobalt-Chromium (Co-Cr) Presillion™ stent for the treatment of high-risk acute myocardial infarction (MI) patients., Background: Percutaneous coronary intervention (PCI) with stent represents the gold standard treatment for acute MI., Methods and Results: We enrolled patients with high-risk acute MI (either ST-segment elevation MI or non-ST-segment elevation MI) treated with PCI using a new Co-Cr bare metal stent with closed cells design and limited balloon compliance. We considered high-risk features as one of the following: age ≥ 70 years, ejection fraction ≤ 35%, glomerular filtration rate ≤ 60 mL/min, diabetes mellitus, rescue PCI, or chronic atrial fibrillation or other conditions requiring long-term oral anticoagulation therapy. Primary outcome of the study was rate of major adverse cardiac events (MACE) defined as all-cause death, new MI, and target-vessel revascularization. A total of 129 consecutive patients were enrolled (69 ± 11 years, 74% men): 71 (55%) patients with ST-segment elevation MI and 58 (45%) patients with non-ST-segment elevation MI. A total of 153 vessels (169 lesions and 179 stents) were treated. The device success rate was high (98.8%). In-hospital MACE rate was 5.4% mainly because of death associated with the acute MI. At 1-year follow-up, the MACE rate was 17.3%, with 11% all-cause death (7.9% of cardiac origin), 0.6% of stent thrombosis, and 4.6% target-vessel revascularization., Conclusions: The use of the Co-Cr Presillion stent in patients with high-risk acute MI treated invasively seems to be safe and efficacious with optimal deliverability and good long-term outcomes and represents a good option in the treatment of these patients., (Copyright © 2011 Wiley-Liss, Inc.)

In this study, we analysed the expression of the transcriptional coactivator TAZ (transcriptional co-activator with PDZ-binding motif), also named WWTR1, in a panel of papillary thyroid carcinoma samples and we observed a significant deregulation of its expression in such tumours. Specifically, by quantitative real-time PCR (qRT-PCR) we evaluated TAZ mRNA levels in tissue specimens (n=61) of papillary thyroid carcinoma (PTC) and herein we show that the PTC samples express much higher TAZ mRNA levels with respect to the normal thyroid tissue (p<0.001). TAZ expression was also evaluated in normal (n=10) and pathological human thyroids (n=17) by immunohistochemical analysis and the increase of TAZ protein levels in PTC was confirmed. To further analyse the molecular mechanisms underlying TAZ overexpression in PTC, we used an inducible system consisting of FRTL-5 rat thyroid cells expressing a conditional RAS oncoprotein and we show that the activation of the RAS signalling pathway is involved in TAZ deregulation. These observations suggest that the activated effectors of the RAS/RAF/MEK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) signalling pathway are involved in the increased expression of TAZ, supporting the idea that this may also occur in thyroid papillary carcinoma. Moreover, we demonstrated that the overexpression of TAZ is able to confer growth advantage to thyroid cells in culture and to induce epithelial-mesenchymal transition. In conclusion, these findings support a potential role for TAZ in the pathogenesis of papillary thyroid carcinomas., (Copyright © 2010 Elsevier Ltd. All rights reserved.)