Early events of basal cell carcinoma (BCC) tumorigenesis are triggered by inappropriate activation of SHH signaling, via the loss of Patched1 (Ptch1) or by activating mutations of Smoothened (Smo). TBX1 is a key regulator of pharyngeal development, mainly through expression in multipotent progenitor cells of the cardiopharyngeal lineage. This transcription factor is connected to several major signaling systems, such as FGF, WNT, and SHH, and it has been linked to cell proliferation and to the regulation of cell shape and cell dynamics. Here, we show that TBX1 was expressed in all of the 51 BCC samples that we have tested, while in healthy human skin it was only expressed in the hair follicle. Signal intensity and distribution was heterogeneous among tumor samples. Experiments performed on a cellular model of mouse BCC showed that Tbx1 is downstream to GLI2, a factor in the SHH signaling, and that, in turn, it regulates the expression of Dvl2, which encodes an adaptor protein that is necessary for the transduction of WNT signaling. Consistently, Tbx1 depletion in the cellular model significantly reduced cell migration. These results suggest that TBX1 is part of a core transcription network that promotes BCC tumorigenesis.
The emergence of ionotronic materials has been recently exploited for interfacing electronics and biological tissues, improving sensing with the surrounding environment. In this paper, we investigated the synergistic effect of regenerated silk fibroin (RS) with a plant-derived polyphenol (i.e., chestnut tannin) on ionic conductivity and how water molecules play critical roles in regulating ion mobility in these materials. In particular, we observed that adding tannin to RS increases the ionic conductivity, and this phenomenon is accentuated by increasing the hydration. We also demonstrated how silk-based hybrids could be used as building materials for scaffolds where human fibroblast and neural progenitor cells can highly proliferate. Finally, after proving their biocompatibility, RS hybrids demonstrate excellent three-dimensional (3D) printability via extrusion-based 3D printing to fabricate a soft sensor that can detect charged objects by sensing the electric fields that originate from them. These findings pave the way for a viable option for cell culture and novel sensors, with the potential base for tissue engineering and health monitoring.
Background: Early diagnosis is essential in the field of lysosomal storage disorders for the proper management of patients and for starting therapies before irreversible damage occurs, particularly in neurodegenerative conditions. Currently, specific biomarkers for the diagnosis of lysosomal storage disorders are lacking in routine laboratory practice, except for enzymatic tests, which are available only in specialized metabolic centers. Recently, we established a method for measuring and verifying changes in GM1 ganglioside levels in peripheral blood lymphocytes in patients with GM1 gangliosidosis. However, fresh blood is not always available, and using frozen/thawed lymphocytes can lead to inaccurate results. Methods: We used frozen/thawed fibroblasts obtained from stored biopsies to explore the feasibility of fluorescent imaging and flow-cytometric methods to track changes in storage materials in fibroblasts from patients with three lysosomal neurodegenerative conditions: GM1 gangliosidosis, Sialidosis, and Niemann–Pick type C. We used specific markers for each pathology. Results and Conclusions: We demonstrated that with our methods, it is possible to clearly distinguish the levels of accumulated metabolites in fibroblasts from affected and unaffected patients for all the three pathologies considered. Our methods proved to be rapid, sensitive, unbiased, and potentially applicable to other LSDs.
Systemic sclerosis is a connective tissue disease characterized by endothelial dysfunction, hyper reactivity of fibroblasts and immunity abnormality in both humoral and mediated cells. Clinically, in addition to the typical skin involvement, mainly the face and fingers, is frequent involvement of lungs, heart and kidneys. Cardiac involvement, in combination with lung involvement, is considered to be the most important determinant of the prognosis of these patients. Cardiac involvement occurs in 15– 35% of cases but in autopsy surveys the incidence reaches 80%. The case we present concerns a woman of 65 years, admitted in December at the Department of Cardiology of our AOU for an episode of low–output heart failure with epigastralgia, sweating, and breathlessness. The cardiological history was almost silent; instead, it presented a history of chronic thyroiditis and a recent infection with SARS COV 2. The objective examination presented hypokinesis of basal pulmonary fields and pitting edema. The blood tests showed an increase in myocardial necrosis, BNP, creatininemia and inflammatory indices (VES, PCR, beta 2 microglobulin, ferritin, fibrinogen), normocytic normochromic anemia, hypogammaglobulinemia, hyperuricemia and proteinuria and hematuria. The echocardiogram showed severe biventricular dysfunction and moderate–grade mitral insufficiency. A coronary examination was performed that showed epicardial coronary vessels free from significant injury. The cardiac magnetic resonance showed a widespread late enhancement subendocardial of the ventricular and atrial chambers with non–vascular distribution suggestive of pathology on an autoimmune basis. Upon closer examination, multiple small telangiectasias were observed in the face, slight hyperpigmentation of the chest and back, and swelling of the hands. The antibody panel showed positivity of ANA and anti Scl70. The patient was thus addressed to a multi–specialist management in which therefore cardiologist and rheumatologist compare and support the treatment of this pathology with the goal of reducing the high mortality and morbidity that characterizes systemic scleroderma with cardiac involvement.
Background Coronary artery ectasia (CAE) is a relatively frequent finding in patient with ST-elevation myocardial infarction (STEMI) who undergo emergent coronary angiography. However, the long-term outcome of STEMI patients with CAE as compared to Non-CAE has been poorly investigated. Purpose To compare the baseline features and outcome of patients with and without CAE in the clinical setting of STEMI. Methods All patients with STEMI who underwent emergent coronary angiography from January 2012 to December 2017 at our Institution were retrospectively enrolled. Baseline demographic, clinical, instrumental, angiographic and percutaneous coronary intervention (PCI) findings were collected for patients with and without CAE. The study outcome measures were recurrent myocardial infarction (MI) and all-cause death. The propensity score weighting (PSW) technique was used to take into account for potential selection bias in treatment assignment between CAE and Non-CAE groups. Results The study included 534 patients with STEMI (mean age 62.9±12.0 years), 154 were CAE and 380 Non-CAE. The two groups were significantly different in terms of sex (90.9% in CAE vs 72,6% in Non-CAE, p<0.001), diabetes (11.7% vs. 25.8%; p=0.009) and smoking status (72.1% vs. 62.4%; p=0.042). The right coronary artery was more commonly treated in CAE patients (41.6% vs. 30.8%, p=0.023) and, as expected, the stent diameter (p<0.001) and the TIMI frame count (p<0.001) were significantly higher in CAE group. The myocardial blush grade was higher in Non-CAE (p<0.001). The Kaplan-Meyer analysis showed a comparable rate of all-cause death among the two groups (3.4/100 person/years in CAE vs. 3.5 per 100 person/years in Non-CAE, Log-Rank = 0.86). The survival free from recurrent MI was lower, although not statistically significant, in CAE vs. Non-CAE patients (3.1/100 person/years vs. 4.8/100 person/years; Log-Rank = 0.068). After PSW, an optimal balance was obtained as demonstrated by a standardized mean difference <0.1 for all the variables included in the model. The adjusted Cox regression analysis showed a significantly higher risk of recurrent MI in CAE vs. Non-CAE groups (HR = 1.93; p=0.009). No difference in the risk of all-cause death was observed (HR = 0.83, p=0.501). Conclusions Patient with STEMI and angiographic evidence of CAE have a different clinical profile compared to Non-CAE. In this analysis focused on STEMI patients, CAE was associated with a higher risk of recurrent MI at long-term follow-up. Funding Acknowledgement Type of funding source: None
Aims Although right ventricular (RV) systolic dysfunction seems to be associated with adverse outcome after transcatheter edge-to-edge mitral valve repair (TEER) with the MitraClip system, the prognostic value of RV free wall longitudinal strain (RVFWLS) in this setting has not been yet investigated. The aim of this study is to evaluate RVFWLS as predictor of outcome in patients with severe or moderate-to-severe functional MR undergoing TEER and its prognostic role compared with tricuspid annular plane systolic excursion (TAPSE). Methods and results 102 patients [73 (IQR: 66.8–77.0) years, 73 males (71.6%)] were retrospectively selected from March 2012 to February 2021. Echocardiograms were performed by using General Electric machines. RVFWLS was assessed through RV modified apical 4-chamber view, setting the region of interest to minimum size. Values of RVFWLS > −20% were recognized as abnormal. We considered a composite endpoint including rehospitalization for heart failure (HF) and overall death as primary outcome. Secondary outcomes were overall death, cardiac death and rehospitalization for HF. All patients were assessed at the longest available follow-up [median 22.1 (IQR: 9.7–49.3) months]. Baseline clinical and echocardiographic characteristics are listed in Table 1. Primary outcome was found in 60 (58.8%) patients, while secondary outcomes, i.e. overall death, cardiac death and rehospitalization for HF, were found respectively in 50 (50.0%), 31 (30.4%), and 36 (35.3%) patients. Mean TAPSE was 16.7 ± 4.0 mm and mean RVFWLS was −16.9 ± 6.0%. At univariable analysis both TAPSE (HR: 0.907, CI: 0.848–0.970, P-value: 0.004) and RVFWLS (HR: 0.937, CI: 0.897–0.979, P-value: 0.004) were significantly associated with the primary outcome. Kaplan–Meier survival curves showed that patients with TAPSE <17 mm had a lower survival free from the composite outcome compared with those with TAPSE ≥17 mm (Log-Rank = 0.030); patients with RVFWLS value > −20% also showed a lower survival free from the composite outcome compared with patients with RVFWLS ≤ −20% (Log Rank 0.004). Among patients with preserved RV systolic longitudinal function as indicated by TAPSE ≥ 17 mm, subjects with RVFWLS > −20% had a significantly higher incidence of the composite outcome compare with those with RVFWLS ≤ −20% (Log-Rank = 0.008). Conversely, no difference was found among patients with TAPSE <17 mm. Conclusions RV dysfunction assessed either by TAPSE and RVFWLS is associated with poorer outcome in patients with severe or moderate-to-severe functional MR undergoing TEER. Compared with TAPSE, RVFWLS seems to be superior in identifying patients at higher risk of adverse events during follow-up. Our data encourage the use of this speckle tracking-derived echocardiographic parameter in routinely evaluation of patients with functional MR candidate for TEER.
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