Design and Characterization of Glyceryl Monooleate-Nanostructures Containing Doxorubicin Hydrochloride

Glyceryl monooleate (GMO) is one of the most popular amphiphilic lipids, which, in the presence of dierent amounts of water and a proper amount of stabilizer, can promote the development of well defined, thermodynamically stable nanostructures, called lyotropic liquid crystal dispersions. The aim of this study is based on the design, characterization, and evaluation of the cytotoxicity of lyotropic liquid crystal nanostructures containing a model anticancer drug such as doxorubicin hydrochloride. The drug is eciently retained by the GMO nanosystems by a remote loading approach. The nanostructures prepared with dierent non-ionic surfactants (poloxamers and polysorbates) are characterized by dierent physico-chemical features as a function of several parameters, i.e., serum stability, temperature, and dierent pH values, as well as the amount of cryoprotectants used to obtain suitable freeze-dried systems. The nanostructures prepared with poloxamer 407 used as a stabilizer show an increased toxicity of the entrapped drug on breast cancer cell lines (MCF-7 and MDA-MB-231) due to their ability to sensitize multidrug-resistant (MDR) tumor cells through the inhibition of specific drug eux transporters. Moreover, the interaction between the nanostructures and the cells occurs after just a few hours, evidencing a huge cellular uptake of the nanosystems

Development and In Vivo Evaluation of Multidrug Ultradeformable Vesicles for the Treatment of Skin Inflammation

The aim of this work was to evaluate the effect of two chemically different edge activators, i.e., Tween® 80 and sodium deoxycholate, on (i) the physical, mechanical, and biological properties of ultradeformable vesicles, and (ii) the administration of naproxen sodium-loaded multidrug ultradeformable vesicles for the transdermal route in order to obtain therapeutically meaningful drug concentrations in the target tissues and to potentiate its anti-inflammatory effect by association with the antioxidant drug idebenone. The results obtained in this investigation highlighted a synergistic action between naproxen and idebenone in the treatment of inflammatory disease with a more pronounced anti-inflammatory effect in multidrug ultradeformable vesicles compared to the commercial formulation of Naprosyn® gel. Systems made up of Tween® 80 appeared to be the most suitable in terms of percutaneous permeation and anti-inflammatory activity due to the greater deformability of these vesicles compared to multidrug ultradeformable vesicles with sodium deoxycholate. Our findings are very encouraging and suggest the use of these carriers in the topical treatment of inflammatory diseases

Cardiac amyloidosis: the great pretender

Cardiac amyloidosis (CA) is often misdiagnosed because of both physician-related and disease-related reasons including: fragmented knowledge among different specialties and subspecialties, shortage of centres and specialists dedicated to disease management, erroneous belief it is an incurable disease, rarity of the condition, intrinsic phenotypic heterogeneity, genotypic heterogeneity in transthyretin-related forms and the necessity of target organ tissue histological diagnosis in the vast majority of cases. Pitfalls, incorrect beliefs and deceits challenge not only the path to the diagnosis of CA but also the precise identification of aetiological subtype. The awareness of this condition is the most important prerequisite for the management of the risk of underdiagnoses and misdiagnosis. Almost all clinical, imaging and laboratory tests can be misinterpreted, but fortunately each of these diagnostic steps can also offer diagnostic “red flags” (i.e. highly suggestive findings that can foster the correct diagnostic suspicion and facilitate early, timely diagnosis). This is especially important because outcomes in CA are largely driven by the severity of cardiac dysfunction and emerging therapies are aimed at preventing further amyloid deposition

The real TiO2/HTM interface of solid-state dye solar cells: role of trapped states from a multiscale modelling perspective

We present a multiscale simulation of charge transport in a solid-state dye-sensitized solar cell, where the real morphology between TiO2 and the hole transport material is included

Identification of Exosomal microRNAs and Their Targets in Papillary Thyroid Cancer Cells

The release of molecules in exosomal cargoes is involved in tumor development and progression. We compared the profiles of exosomal microRNAs released by two thyroid cancer cell lines (TPC-1 and K1) with that of non-tumorigenic thyroid cells (Nthy-ori-3-1), and we explored the network of miRNA–target interaction. After extraction and characterization of exosomes, expression levels of microRNAs were investigated using custom TaqMan Advanced array cards, and compared with those expressed in the total cell extracts. The functional enrichment and network-based analysis of the miRNAs’ targets was also performed. Five microRNAs (miR-21-5p, miR-31-5p, miR-221-3p, miR-222-3p, and let-7i-3p) were significantly deregulated in the exosomes of tumor cells vs. non-tumorigenic cells, and three of them (miR-31-5p, miR-222-3p, and let-7i-3p) in the more aggressive K1 compared to TPC-1 cells. The network analysis of the five miRNAs identified some genes as targets of more than one miRNAs. These findings permitted the identification of exosomal microRNAs secreted by aggressive PTC cells, and indicated that their main targets are regulators of the tumor microenvironment. A deeper analysis of the functional role of the targets of exosomal miRNAs will provide further information on novel targets of molecular treatments for these neoplasms

Carpal tunnel syndrome in cardiac amyloidosis: implications for early diagnosis and prognostic role across the spectrum of aetiologies

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Clinical characteristics of wild-type transthyretin cardiac amyloidosis – Disproving myths.

Aims: Wild-type transthyretin amyloidosis (ATTRwt) is mostly considered a disease predominantly of elderly male, characterised by concentric LV hypertrophy, preserved LVEF and low QRS voltages. We sought to describe the characteristics of a large cohort of ATTRwt patients to better define the disease. Methods and Results: Clinical findings of consecutive ATTRwt patients diagnosed at 2 centres were reviewed. ATTRwt was diagnosed histologically or non-invasively (LV hypertrophy 12mm, intense cardiac uptake at 99mTc-DPD scintigraphy and AL exclusion). Mutations in TTR were excluded in all cases. The study cohort comprised 108 patients (78.68 years); 67 (62%) diagnosed invasively and 41 (38%) non-invasively. Twenty patients (19%) were females. An asymmetric hypertrophy pattern was observed in 25 (23%) patients. Mean LVEF was 5214%, with 39 patients (37%) showing a LVEF<50%. Atrial fibrillation (56%) and a pseudo-infarct pattern (63%) were the commonest ECG findings. Only 22 patients fulfilled QRS low-voltage criteria while 10 showed LV hypertrophy on ECG. Although heart failure was the most frequent profile leading to diagnosis (68%), 7% of individuals presented with atrioventricular block and 11% were diagnosed incidentally. Almost one third (35; 32%) were previously misdiagnosed. Conclusion: The clinical spectrum of ATTRwt is heterogeneous and differs from the classic phenotype: women are affected in a significant proportion; asymmetric LV hypertrophy and impaired LVEF are not rare and only a minority have low QRS voltages. Clinicians should be aware of the broad clinical spectrum of ATTRwt to correctly identify an entity for which a number of disease-modifying treatments are under investigation.pre-print833 K

Clinical characteristics of wild-type transthyretin cardiac amyloidosis: disproving myths.

Wild-type transthyretin amyloidosis (ATTRwt) is mostly considered a disease predominantly of elderly male, characterized by concentric LV hypertrophy, preserved LVEF, and low QRS voltages. We sought to describe the characteristics of a large cohort of ATTRwt patients to better define the disease. Clinical findings of consecutive ATTRwt patients diagnosed at 2 centres were reviewed. ATTRwt was diagnosed histologically or non-invasively (LV hypertrophy ≥12 mm, intense cardiac uptake at 99mTc-DPD scintigraphy and AL exclusion). Mutations in TTR were excluded in all cases. The study cohort comprised 108 patients (78.6 ± 8 years); 67 (62%) diagnosed invasively and 41 (38%) non-invasively. Twenty patients (19%) were females. An asymmetric hypertrophy pattern was observed in 25 (23%) patients. Mean LVEF was 52 ± 14%, with 39 patients (37%) showing a LVEF < 50%. Atrial fibrillation (56%) and a pseudo-infarct pattern (63%) were the commonest ECG findings. Only 22 patients fulfilled QRS low-voltage criteria while 10 showed LV hypertrophy on ECG. Although heart failure was the most frequent profile leading to diagnosis (68%), 7% of individuals presented with atrioventricular block and 11% were diagnosed incidentally. Almost one third (35; 32%) were previously misdiagnosed. The clinical spectrum of ATTRwt is heterogeneous and differs from the classic phenotype: women are affected in a significant proportion; asymmetric LV hypertrophy and impaired LVEF are not rare and only a minority have low QRS voltages. Clinicians should be aware of the broad clinical spectrum of ATTRwt to correctly identify an entity for which a number of disease-modifying treatments are under investigation.This work was supported in part by the Spanish Society of Cardiology [Grant 2016 to E.G-L.] and by the Instituto de Salud Carlos III (ISCIII) [grants RD012/0042/0066 and CB16/11/00432] and by the Spanish Ministry of Economy and Competitiveness [grant SAF2015-71863-REDT]. Grants are supported by the Plan Estatal de IþDþI 2013-2016–European Regional Development Fund (FEDER) “A way of making Europe”.S