Osteogenic differentiation of human mesenchymal stem cells by the single action of luminescent polyurea oxide biodendrimers

Fundação para a Ciência e a Tecnologia for financial support through project PTDC/MEC-ONC/29327/2017 and the PhD grant SFRH/BD/109006/2015 (R.F.P.). We also thank Dr. Luisa Maia (UCIBIO, FCT-UNL) for EPR measurements.Polyurea oxide (PURO) biodendrimers are a class of dendrimers that can trigger osteogenic differentiation of human mesenchymal stem cells (hMSCs). PURO biodendrimers are prepared by simple, solventless oxidation of polyurea dendrimers using hydrogen peroxide as the oxidant in quantitative yield, retaining both biocompatibility (up to 10 mg/mL for higher generations) and the non-traditional intrinsic luminescence. The effect of PURO biodendrimers in the differentiation of hMSCs was found by the single addition to a standard growth medium for MSCs differentiation (without differentiation inducers). After 21 days of incubation, the formation of osteoblasts was confirmed by the alizarin red staining assay and alkaline phosphatase activity. This is the first report of in vitro osteodifferentiation fully regulated by synthetic soft polymers such as dendrimers. Current osteogenic differentiation protocols rely on an in vitro inducing formulation (including dexamethasone, ascorbic acid, and β-glycerophosphate), which lacks therapeutic potential in vivo. The outstanding role of dendrimers in nanomedicine, under clinic translation, combined with this feature is envisaged to foster PURO dendrimers as an important strategy in cell therapy and regenerative medicine.publishersversionpublishe

Electron impact ionization of 1-propanol

Experimental measurements of the cations created in electron impact ionization have been undertaken for the primary isomer of propanol using a Hidden Quadrupole Mass Spectrometer (EPIC 300), with a mass resolution of 1 amu. The mass spectra recorded at an incident electron energy of 70 eV reveals the relative probability of forming 50 different cations, by either direct ionization or dissociative ionization. Individual partial ionization cross sections (PICS) for 31 different cations were measured for the first time in this work, for the incident electron energy range from 10 to 100eV. Also, appearance energies (AEs) and Wannier exponents for the 16 most intense cations formed in electron collisions with 1-propanol are reported. Where possible, those results are compared to those from an earlier investigation. Total Ionization Cross Sections (TICS) were also obtained from the sum of the measured PICS, for nearly all cations measured, and are compared to relevant data reported in the literature. In addition, as a part of this study, theoretical TICS were calculated using the Binary-encounter Bethe (BEB) and independent atom model with screening corrected additivity rule (IAM - SCAR) methods. Good agreement between current measured and calculated TICSs and corresponding earlier results was typically found

Novel Perspectives in Management of Angiogenesis and Cancer Therapy

Funding: The project was funded by IPOLFG EPE and by iNOVA4Health (UID/Multi/04462/2019) a program financially supported by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência, through national funds. We also acknowledge funding from FCT-MCTES through the project DREAM—PTDC/MEC-ONC/29327/2017. FL-C PhD fellowship was funded by FCT (PD/BD/128337/2017).The activation of endothelial cells (ECs) is a crucial step on the road map of tumor angiogenesis and expanding evidence indicates that a pro-oxidant tumor microenvironment, conditioned by cancer metabolic rewiring, is a relevant controller of this process. Herein, we investigated the contribution of oxidative stress-induced ferroptosis to ECs activation. Moreover, we also addressed the anti-angiogenic effect of Propranolol. We observed that a ferroptosis-like mechanism, induced by xCT inhibition with Erastin, at a non-lethal level, promoted features of ECs activation, such as proliferation, migration and vessel-like structures formation, concomitantly with the depletion of reduced glutathione (GSH) and increased levels of oxidative stress and lipid peroxides. Additionally, this ferroptosis-like mechanism promoted vascular endothelial cadherin (VE-cadherin) junctional gaps and potentiated cancer cell adhesion to ECs and transendothelial migration. Propranolol was able to revert Erastin-dependent activation of ECs and increased levels of hydrogen sulfide (H2S) underlie the mechanism of action of Propranolol. Furthermore, we tested a dual-effect therapy by promoting ECs stability with Propranolol and boosting oxidative stress to induce cancer cell death with a nanoformulation comprising selenium-containing chrysin (SeChry) encapsulated in a fourth generation polyurea dendrimer (SeChry@PUREG4). Our data showed that novel developments in cancer treatment may rely on multi-targeting strategies focusing on nanoformulations for a safer induction of cancer cell death, taking advantage of tumor vasculature stabilization.publishersversionpublishe

Metabolic profiling and combined therapeutic strategies unveil the cytotoxic potential of selenium-chrysin (SeChry) in NSCLC cells

Funding Information: The institutions are funded by Fundac\u00B8 \u00E3o para a Ci\u00EAncia e a Tecnologia/Minist\u00E9rio da Ci\u00EAncia, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNO-VA4Health [grant numbers UIDB/04462/2020 and UIDP/04462/2020], to MOSTMICRO-ITQB [grant numbers UIDB/04612/2020 and UIDP/04612/2020] and the Associated Laboratory LS4FUTURE [grant number LA/P/0087/2020]. During the course of PhD, Cindy Mendes was funded by Liga Portuguesa Contra o Cancro -Nucleo regional Sul (LPCC-NRS) and by an FCT individual Ph.D. fellowship [grant number 2020.06956.BD]. Isabel Lemos was funded by an FCT individual Ph.D. fellowship [grant number UI/BD/154203/2022]. Ana Hip\u00F3lito was funded by a FCT individual Ph.D. fellowship [grant number SFRH/BD/148441/2019]. Filipa Martins was funded by a FCT individual Ph.D. fellowship (2020.04780.BD). Luis G. Gonc\u00B8 alves was financed by a FCT contract according to DL57/2016, [grant number SFRH/BPD/111100/2015]. This work benefited from access to CERMAX, ITQB-NOVA, Oeiras, Portugal with equipment funded by FCT, project AAC 01/SAICT/2016. Publisher Copyright: © 2024 The Author(s).Lung cancer ranks as the predominant cause of cancer-related mortalities on a global scale. Despite progress in therapeutic interventions, encompassing surgical procedures, radiation, chemotherapy, targeted therapies and immunotherapy, the overall prognosis remains unfavorable. Imbalances in redox equilibrium and disrupted redox signaling, common traits in tumors, play crucial roles in malignant progression and treatment resistance. Cancer cells, often characterized by persistent high levels of reactive oxygen species (ROS) resulting from genetic, metabolic, and microenvironmental alterations, counterbalance this by enhancing their antioxidant capacity. Cysteine availability emerges as a critical factor in chemoresistance, shaping the survival dynamics of non-small cell lung cancer (NSCLC) cells. Selenium-chrysin (SeChry) was disclosed as a modulator of cysteine intracellular availability. This study comprehensively characterizes the metabolism of SeChry and investigates its cytotoxic effects in NSCLC. SeChry treatment induces notable metabolic shifts, particularly in selenocompound metabolism, impacting crucial pathways such as glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, and amino acid metabolism. Additionally, SeChry affects the levels of key metabolites such as acetate, lactate, glucose, and amino acids, contributing to disruptions in redox homeostasis and cellular biosynthesis. The combination of SeChry with other treatments, such as glycolysis inhibition and chemotherapy, results in greater efficacy. Furthermore, by exploiting NSCLC’s capacity to consume lactate, the use of lactic acid-conjugated dendrimer nanoparticles for SeChry delivery is investigated, showing specificity to cancer cells expressing monocarboxylate transporters.publishersversionpublishe

Electron impact ionization of 1-propanol

10 pags., 5 figs., 3 tabs.Experimental measurements of the cations created in electron impact ionization have been undertaken for the primary isomer of propanol using a Hidden Quadrupole Mass Spectrometer (EPIC 300), with a mass resolution of 1 amu. The mass spectra recorded at an incident electron energy of 70 eV reveals the relative probability of forming 50 different cations, by either direct ionization or dissociative ionization. Individual partial ionization cross sections (PICS) for 31 different cations were measured for the first time in this work, for the incident electron energy range from 10 to 100 eV. Also, appearance energies (AEs) and Wannier exponents for the 16 most intense cations formed in electron collisions with 1-propanol are reported. Where possible, those results are compared to those from an earlier investigation. Total Ionization Cross Sections (TICS) were also obtained from the sum of the measured PICS, for nearly all cations measured, and are compared to relevant data reported in the literature. In addition, as a part of this study, theoretical TICS were calculated using the Binary-encounter Bethe (BEB) and independent atom model with screening corrected additivity rule (IAM–SCAR) methods. Good agreement between current measured and calculated TICSs and corresponding earlier results was typically found.M.C.A.L. acknowledges financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq),Fundacão de Amparo à Pesquisa do Estado de Minas Gerais(FAPEMIG) and FINEP (under project CT-Infra), while M.J.B. thanks CNPq for his “Special Visiting Professor” award. K.L.N. thanks CNPq for an “Attracting Young Talent Grant” under the “Science WithoutBorders” program. Some financial assistance from the Australian Research Council is also noted. Finally, S. Ghosh acknowledges forhis grant from PNPD/CAPES while G. Garcia thanks the Spanish Ministerio de Economia, Industria y Competitividad for his projectgrant FIS 2016 −80440 and the EU project FP7-ITN – ARGENT –608163.Peer Reviewe

The yield of head CT in syncope: a pilot study

Although head CT is often routinely performed in emergency department (ED) patients with syncope, few studies have assessed its value