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Extracellular vesicles from 2D and 3D culture models exhibit distinct glycan profiles
No full textIntroduction: Glycosylation, a crucial post-translational protein modification, plays a key role in modulation of protein function, contributing to various stages of tumourigenesis. Studies have shown that tumour-derived extracellular vesicles (tEVs) have an altered glycoprofile, including distinct glycosylation patterns which may have utility as tumour biomarkers. Current research predominantly relies on monolayer cultures (2D). This study investigates whether tEVs isolated from 3D culture models, which should be more like in vivo conditions, display distinct glycan profiles compared to those isolated from 2D ones.
Methods: The human ovarian (ES-2) and breast (MDA-MB-231, MCF-7) cancer cell lines were cultured using 2D and 3D
culture models. For the 3D cultures, spheroids were formed by the hanging drop method(MDA-MB-231) or ultra-low attachment plates (ES-2, MCF-7) and then moved to Petri dishes coated with an anti-adhesion solution. EVs were isolated from both culture models’ supernatants by differential centrifugation. Their characterization involved TEM, NTA, andWestern Blot as per MISEV 2023 guidelines. The EVs glycosylation profile was assessed by a lectin-based affinity approach using an adapted ELISA assay (lectins analysed: PNA, SBA, UEA I, GSL I, GSL II, PSA, WGA, WGA succynilated, DBA-LCA, PHA-L).
Results: The presence of EVs in the supernatant from both cell culture models was verified for all cell lines, and the EV
identity was confirmed by characterization. The ELISA assay showed significant differences in glycan lectin-soundedness, indicating distinct enrichment profiles in EVs derived from the different culturemodels: in 3D-EVs, compared to 2D-EVs, glycans recognized by PNA, UEA I, and succinylated WGA in MDA and UEA I, DBA, and GSL II in MCF-7 decreased by approximately 50%; conversely, an increase of roughly 30% was observed for succinylated WGA, WGA, and PHA-L in ES-2. Differences for PNA, UEA I, WGA succinylated, and LCA were also evident when comparing MDA (higher aggressiveness) to MCF-7 (lower aggressiveness) 3D- EVs.
Summary/Conclusion: The data suggests that the different cellular organizations lead to different glycan profiles of isolated EVs, which may exert a variable impact on their evaluation as potential cancer biomarkers and, hypothetically, affect their biological functions.
Funding: This study was supported by the Funded by FFORIC24.23 to IG, Department of Life, Health and Environmental Science
Nonlinear Dynamics of Beam-Like Thin Tubes Considering Cross-Sectional Flattening and Longitudinal Stretch
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Elective First-Line Use of Dimethyl Fumarate in Psoriasis: Insights from an Italian Cohort
Get PDFIntroduction: Dimethyl fumarate (DMF) is an approved conventional systemic treatment for psoriasis that does not exhibit any drug–drug interactions or cumulative organ toxicities. Aim: This retrospective real-world study aimed to analyze the long-term efficacy, safety, and tolerability of DMF in patients with moderate psoriasis. Methods: Data on safety and efficacy were collected from medical charts. The effect on disease severity was assessed using the Psoriasis Area Severity Index. Results: Our study included 148 patients over a 48-week treatment period, confirming DMF as an effective option in the treatment of moderate psoriasis. Adverse events were only mild or moderate, principally flushing, epigastralgia, and diarrhea. However, DMF exhibited a delayed onset of action, and the dropout rate was high. These aspects highlight the importance of educating patients about the activity profile of DMF, the potential occurrence of side effects, and their management. However, side effects are self-limiting with discontinuation of treatment and generally occur early, allowing patients to be promptly switched to other therapies if DMF is not tolerated. Conclusions: Our results confirm that DMF may be offered as a first-line treatment for moderate psoriasis as it demonstrated efficacy even in the long-term, when treatment is tolerated, especially in patients with a disease duration of less than five years. DMF may also be proposed when the patient presents comorbidities, when immunosuppression is undesired, and/or before the initiation of biological therapies
Contractivity of stochastic θ-methods under non-global Lipschitz conditions
Get PDFThe paper is devoted to address the numerical preservation of the exponential mean-square contractive character of the dynamics of stochastic differential equations (SDEs), whose drift and diffusion coefficients are subject to non-global Lipschitz assumptions. The conservative attitude of stochastic θ-methods is analyzed both for Itô and Stratonovich SDEs. The case of systems with linear drift is also analyzed in terms of spectral properties of the coefficient matrix of the drift. Numerical evidence on selected test problems confirms the effectiveness of the approach
Editorial: Impacts of the extreme Gannon geomagnetic storm of May 2024 throughout the magnetosphere-ionosphere-thermosphere system
Get PDFSpecial Issue on Edge Intelligence Software Systems for Internet of Autonomous Unmanned Vehicles Journal of Software: Practice and Experience (Wiley Press)
No full textA Systematic Method for the Calibration of FEA Model of Synchronous Reluctance Machines Considering Manufacturing Effects
Get PDFThe recent advances in computational power and motor design software, supported by finite elements analysis (FEA), permit accurate prediction of the losses and electromagnetic performance of the machine at the design stage. Anyway, the simulation accuracy strictly depends on the real motor geometry and material properties, which are affected by the manufacturing process. This article offers a systematic method for accurately calibrating the electromagnetic FEA models, permitting to consider the production process within the motor design stage. A synchronous reluctance motor prototype is designed, manufactured, and experimentally characterized, and the measured flux and torque characteristics are exploited for ex-post calibrating the FEA model of the machine. This approach led to a reduction in torque estimation error from 18% to 4%, and an improvement of the flux maps evaluation, thus enhancing and validating the design procedure and permitting further optimization steps of machines with similar geometry and dimensions. The effects are particularly evident in the proposed motor due to the reduced size of the rotor flux barriers, stator teeth, and yoke. The mechanical tolerances are analyzed through a Monte Carlo analysis covering different areas of the machine. Then, the effects of uncertain airgap length and iron degradation due to the manufacturing process are considered, determining an equivalent degraded BH curve
Clinical characteristics and outcomes of ischemic stroke despite appropriate oral anticoagulation for atrial fibrillation: A systematic review and meta-analysis of real-world studies
Get PDFBackground: Despite appropriate oral anticoagulants (OACs) use to prevent cardioembolism in atrial fibrillation (AF) and thromboembolic conditions, some patients still experience ischemic stroke. Objectives: This systematic review and meta-analysis aimed to investigate clinical characteristics and outcomes of ischemic stroke occurring despite appropriate OACs use for atrial fibrillation, comparing direct oral anticoagulants (DOACs) with vitamin K antagonists (VKAs). Methods: A systematic search of PubMed and Scopus identified observational cohort studies published in English until October 2, 2024, on ischemic stroke patients on appropriate OAC doses. We utilized random-effects modeling to assess the impact of stroke severity, anticoagulant type, and revascularization on in-hospital mortality, 90-day functional recovery (modified Rankin Scale [mRS] 0–2), 90-day stroke recurrence, and intracranial hemorrhage (ICH). Results: Out of 25,985 articles screened, 11 studies (14 cohorts) involving 10,624 patients were included. The mean age was 76 years, with median National Institute of Health Stroke Scale (NIHSS) score of 5.1. Prevalent risk factors included hypertension (78.3%), dyslipidemia (44.3%), and prior stroke or TIA (55.6%). No significant baseline differences were found by OAC type, except for higher coronary heart disease prevalence in the VKA group. DOAC patients showed better 90-day functional outcomes than VKA patients (60.4% vs. 35.7%; p = 0.048). Meta-regression did not identify significant predictors for in-hospital death or 90-day favorable outcomes. Conclusions: Ischemic stroke patients despite OACs exhibited a high burden of vascular risk factors and moderate stroke severity. DOAC-related strokes showed better 90-day functional outcomes than those on VKA. Further research on long-term prognosis is needed
IRON AGE HOARDS IN THE ITALIAN PENINSULA AND SARDINIA: A REVIEW
No full textIt is definitely key and appropriate to achieve a focus on the interconnecting functions
of the hoards and the single depositions of metal objects. In this general framework, this
paper aims to offer an overview of the Iron Age finds in continental Italy, apart from Sicily: attention is concentrated on the central regions of the country, including Sardinia. In this perspective, Central Italy has more similarities with the northern than with the southern regions of the country. The metal depositions in the southern regions offer an almost homogeneous picture and several are commonly dated to 8th century BC. On the contrary,
with the exceptions of a new find in Piedmont and of the huge hoard of San Francesco in
Bologna, metal deposits in northern Italy belong mostly to 5th century BC. As usual, it is
very important to connect each find to the general knowledge about the findplace and so gain exhaustive interpretations of both