The new H2S-releasing compound ACS94 exerts protective effects through the modulation of thiol homoeostasis

The synthesis of a new dithiolethione-cysteine ethyl ester hybrid, ACS94, its metabolites, and its effect on GSH levels in rat tissues and on the concentration of circulating H2S is described. ACS94 rapidly enters the cells, where it is metabolised to cysteine and the dithiolethione moiety ACS48. Experiments performed through the oral administration of ACS94 to healthy rats showed that it is capable of increasing the GSH levels in most of the analysed organs and the concentration of circulating H2S. Although the increase in GSH concentration was similar to that obtained by ACS48 and N-acetylcysteine ethyl ester, the H2S increase was long-lasting and more evident with respect to the parent molecules. Moreover, a decrease of homocysteine in several rat organs and in plasma was noted. This effect may represent a potential therapeutic use of ACS94, as hyperhomocysteinaemia is considered a risk factor for cardiovascular diseases. Lastly, ACS94 was more efficient than N-acetylcysteine in protecting the liver and kidneys against acute acetaminophen toxicity

Immune thrombotic thrombocytopenic purpura: Personalized therapy using ADAMTS-13 activity and autoantibodies

Recently, treatment of immune-mediated thrombotic thrombocytopenic purpura (ITTP) has changed with the advent of caplacizumab in clinical practice. The International Working Group (IWG) has recently integrated the ADAMTS-13 activity/autoantibody monitoring in consensus outcome definitions. We report three ITTP cases during the coronavirus disease 2019 pandemic, that received a systematic evaluation of ADAMTS-13 activity and autoantibodies. We describe how the introduction of caplacizumab and ADAMTS-13 monitoring could change the management of ITTP patients and discuss whether therapeutic choices should be based on the clinical response alone. ADAMTS-13 activity/antibodies were assessed every 5 days. Responses were evaluated according to updated IWG outcome definitions. These kinetics, rather than clinical remission, guided the therapy, allowing early and safe caplacizumab discontinuation and sensible administration of rituximab. Caplacizumab was cautiously discontinued after achieving ADAMTS-13 complete remission. These cases illustrate that prospective ADAMTS-13 evaluation and use of updated IWG definitions may improve real-life patients’ management in the caplacizumab era

Deposition and characterization of niobium films for SRF cavity application

Niobium coated copper cavities are an interesting alternative to bulk niobium ones for Superconducting Radio Frequency (SRF) applications to particle accelerators. The magnetron sputtering is the technology developed at CERN for depositing niobium Alms and applied over the past twenty years. Unfortunately, the observed degradation of the quality factor with increasing cavity voltage, not completely understood, prevents the use of this technology in future large accelerators designed to work at gradients higher than 30 MWm, with quality factors of the order of 1010 (or higher). At the beginning of the new millennium some new deposition techniques have been proposed to overcome the difficulties encountered with the sputtering technique. This paper compares the properties of niobium films obtained with the magnetron sputtering and with a cathodic arc deposition in ultra-high vacuum (UHVCA). The UHVCA-produced Nb Alms have structural and transport properties closer to the bulk ones, providing a promising alternative for niobium coated, highvoltage and high-Q copper RF cavities, with respect to the standard magnetron sputtering technique. Preliminary results and possible approaches to whole cavity UHVCA coating will be presented and discussed

Therapeutic effect of hydrogen sulfide-releasing L-dopa derivative ACS84 on 6-OHDA-induced Parkinson's disease rat model

Parkinson's disease (PD), characterized by loss of dopaminergic neurons in the substantia nigra, is a neurodegenerative disorder of central nervous system. The present study was designed to investigate the therapeutic effect of ACS84, a hydrogen sulfide-releasing-L-Dopa derivative compound, in a 6-hydroxydopamine (6-OHDA)-induced PD model. ACS84 protected the SH-SY5Y cells against 6-OHDA-induced cell injury and oxidative stress. The protective effect resulted from stimulation of Nrf-2 nuclear translocation and promotion of anti-oxidant enzymes expression. In the 6-OHDA-induced PD rat model, intragastric administration of ACS84 relieved the movement dysfunction of the model animals. Immunofluorescence staining and High-performance liquid chromatography analysis showed that ACS84 alleviated the loss of tyrosine-hydroxylase positive neurons in the substantia nigra and the declined dopamine concentration in the injured striatums of the 6-OHDA-induced PD model. Moreover, ACS84 reversed the elevated malondialdehyde level and the decreased glutathione level in vivo. In conclusion, ACS84 may prevent neurodegeneration via the anti-oxidative mechanism and has potential therapeutic values for Parkinson's disease

Effects of a diet based on foods from symbiotic agriculture on the gut microbiota of subjects at risk for metabolic syndrome

none18noDiet is a major driver of gut microbiota variation and plays a role in metabolic disorders, including metabolic syndrome (MS). Mycorrhized foods from symbiotic agriculture (SA) exhibit improved nutritional properties, but potential benefits have never been investigated in humans. We conducted a pilot interventional study on 60 adults with ≥ 1 risk factors for MS, of whom 33 consumed SA‐derived fresh foods and 27 received probiotics over 30 days, with a 15‐day follow‐up. Stool, urine and blood were collected over time to explore changes in gut microbiota, metabolome, and biochemical, inflammatory and immunologic parameters; previous dietary habits were investigated through a validated food‐frequency questionnaire. The baseline microbiota showed alterations typical of metabolic disorders, mainly an increase in Coriobacteriaceae and a decrease in health-associated taxa, which were partly reversed after the SA‐based diet. Improvements were observed in metabolome, MS presence (two out of six subjects no longer had MS) or components. Changes were more pronounced with less healthy baseline diets. Probiotics had a marginal, not entirely fa-vorable, effect, although one out of three subjects no longer suffered from MS. These findings sug-gest that improved dietary patterns can modulate the host microbiota and metabolome, counteract-ing the risk of developing MS.openTurroni S.; Petracci E.; Edefonti V.; Giudetti A.M.; D'amico F.; Paganelli L.; Giovannetti G.; Del Coco L.; Fanizzi F.P.; Rampelli S.; Guerra D.; Rengucci C.; Bulgarelli J.; Tazzari M.; Pellegrini N.; Ferraroni M.; Nanni O.; Serra P.Turroni, S.; Petracci, E.; Edefonti, V.; Giudetti, A. M.; D'Amico, F.; Paganelli, L.; Giovannetti, G.; Del Coco, L.; Fanizzi, F. P.; Rampelli, S.; Guerra, D.; Rengucci, C.; Bulgarelli, J.; Tazzari, M.; Pellegrini, N.; Ferraroni, M.; Nanni, O.; Serra, P

Effects of a diet based on foods from symbiotic agriculture on the gut microbiota of subjects at risk for metabolic syndrome

Diet is a major driver of gut microbiota variation and plays a role in metabolic disorders, including metabolic syndrome (MS). Mycorrhized foods from symbiotic agriculture (SA) exhibit improved nutritional properties, but potential benefits have never been investigated in humans. We conducted a pilot interventional study on 60 adults with 65 1 risk factors for MS, of whom 33 consumed SA\u2010derived fresh foods and 27 received probiotics over 30 days, with a 15\u2010day follow\u2010up. Stool, urine and blood were collected over time to explore changes in gut microbiota, metabolome, and biochemical, inflammatory and immunologic parameters; previous dietary habits were investigated through a validated food\u2010frequency questionnaire. The baseline microbiota showed alterations typical of metabolic disorders, mainly an increase in Coriobacteriaceae and a decrease in health-associated taxa, which were partly reversed after the SA\u2010based diet. Improvements were observed in metabolome, MS presence (two out of six subjects no longer had MS) or components. Changes were more pronounced with less healthy baseline diets. Probiotics had a marginal, not entirely fa-vorable, effect, although one out of three subjects no longer suffered from MS. These findings sug-gest that improved dietary patterns can modulate the host microbiota and metabolome, counteract-ing the risk of developing MS

Circulating extracellular particles from severe COVID-19 patients show altered profiling and innate lymphoid cell-modulating ability

Introduction: Extracellular vesicles (EVs) and particles (EPs) represent reliable biomarkers for disease detection. Their role in the inflammatory microenvironment of severe COVID-19 patients is not well determined. Here, we characterized the immunophenotype, the lipidomic cargo and the functional activity of circulating EPs from severe COVID-19 patients (Co-19-EPs) and healthy controls (HC-EPs) correlating the data with the clinical parameters including the partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) and the sequential organ failure assessment (SOFA) score. Methods: Peripheral blood (PB) was collected from COVID-19 patients (n=10) and HC (n=10). EPs were purified from platelet-poor plasma by size exclusion chromatography (SEC) and ultrafiltration. Plasma cytokines and EPs were characterized by multiplex bead-based assay. Quantitative lipidomic profiling of EPs was performed by liquid chromatography/mass spectrometry combined with quadrupole time-of-flight (LC/MS Q-TOF). Innate lymphoid cells (ILC) were characterized by flow cytometry after co-cultures with HC-EPs or Co-19-EPs. Results: We observed that EPs from severe COVID-19 patients: 1) display an altered surface signature as assessed by multiplex protein analysis; 2) are characterized by distinct lipidomic profiling; 3) show correlations between lipidomic profiling and disease aggressiveness scores; 4) fail to dampen type 2 innate lymphoid cells (ILC2) cytokine secretion. As a consequence, ILC2 from severe COVID-19 patients show a more activated phenotype due to the presence of Co-19-EPs. Discussion: In summary, these data highlight that abnormal circulating EPs promote ILC2-driven inflammatory signals in severe COVID-19 patients and support further exploration to unravel the role of EPs (and EVs) in COVID-19 pathogenesis