Antimetastatic properties on both murine and human osteosarcoma cell lines (POS-1 and KHOS) have been evidenced using exopolysaccharide (EPS) derivatives, produced by Alteromonas infernus bacterium. These derivatives had no significant effect on the cell cycle neither a pro-apoptotic effect on osteosarcoma cells. Based on this observation, these EPSs could be employed as new drug delivery systems for therapeutic uses. A theranostic approach, i.e., combination of a predictive biomarker with a therapeutic agent, has been developed notably by combining with true pair of theranostic radionuclides, such as scandium 47Sc/44Sc. However, it is crucial to ensure that, once complexation is done, the biological properties of the vector remain intact, allowing the molecular tropism of the ligand to recognize its molecular target. It is important to assess if the biological properties of EPS evidenced on osteosarcoma cell lines remain when scandium is complexed to the polymers and can be extended to other cancer cell types. Scandium-EPS complexes were thus tested in vitro on human cell lines: MNNG/HOS osteosarcoma, A375 melanoma, A549 lung adenocarcinoma, U251 glioma, MDA231 breast cancer, and Caco2 colon cancer cells. An xCELLigence Real Cell Time Analysis (RTCA) technology assay was used to monitor for 160 h, the proliferation kinetics of the different cell lines. The tested complexes exhibited an anti-proliferative effect, this effect was more effective compared to EPS alone. This increase of the antiproliferative properties was explained by a change in conformation of EPS complexes due to their polyelectrolyte nature that was induced by complexation. Alterations of both growth factor-receptor signaling, and transmembrane protein interactions could be the principal cause of the antiproliferative effect. These results are very promising and reveal that EPS can be coupled to scandium for improving its biological effects and also suggesting that no major structural modification occurs on the ligand.
The specific effects of gestational diabetes mellitus (GDM) on twin pregnancy outcomes, which are at high risk per se, are unclear. The present study analyzes outcomes of twin pregnancies complicated by GDM (n = 227) by comparing them with GDM singleton pregnancies (n = 1060) and with twin pregnancies without GDM (n = 1008), all followed up at Sant’Anna Hospital, Turin (Italy), between January 2010 and March 2020. The prevalence of GDM among twin pregnancies (n = 1235) was 18.4%. Compared to GDM singletons, GDM twins had higher rates of preeclampsia (aOR 2.0; 95% CI 1.2–3.8), cesarean section (aOR 7.5; 95% CI 5.2–10.8), and neonatal hypoglycemia (aOR 2.5; 95% CI 1.1–5.3). They had a higher incidence of abnormal 2 h OGTT values (aOR 7.1; 95% CI: 3.2–15.7) and were less likely to require insulin therapy (aOR 0.5; 95% CI: 0.3–0.7). In comparison with twin pregnancies without GDM, women with GDM twins were significantly older (35.0 vs. 33.0 years; p < 0.001) and had higher BMI (23.0 versus 22.0 kg/m2; p < 0.001); they had a higher incidence of LGA newborns (aOR 5.3; 95% CI 1.7–14.8), and lower incidence of low APGAR scores (0.5; 95% CI 0.3–0.9). Overall, GDM does not worsen outcomes of twin pregnancy, which is per se at high risk for adverse outcomes.
(1) Background: Exopolysaccharide (EPS) derivatives, produced by Alteromonas infernus bacterium, showed anti-metastatic properties. They may represent a new class of ligands to be combined with theranostic radionuclides, such as 47Sc/44Sc. The goal of this work was to investigate the feasibility of such coupling. (2) Methods: EPSs, as well as heparin used as a drug reference, were characterized in terms of molar mass and dispersity using Asymmetrical Flow Field-Flow Fractionation coupled to Multi-Angle Light Scattering (AF4-MALS). The intrinsic viscosity of EPSs at different ionic strengths were measured in order to establish the conformation. To determine the stability constants of Sc with EPS and heparin, a Free-ion selective radiotracer extraction (FISRE) method has been used. (3) Results: AF4-MALS showed that radical depolymerization produces monodisperse EPSs, suitable for therapeutic use. EPS conformation exhibited a lower hydrodynamic volume for the highest ionic strengths. The resulting random-coiled conformation could affect the complexation with metal for high concentration. The LogK of Sc-EPS complexes have been determined and showing that they are comparable to the Sc-Hep. (4) Conclusions: EPSs are very promising to be coupled with the theranostic pair of scandium for Nuclear Medicine.
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