Reduced Levels of H₂S in Diabetes-Associated Osteoarthritis Are Linked to Hyperglycaemia, Nrf-2/HO-1 Signalling Downregulation and Chondrocyte Dysfunction

[Abstract] Different findings indicate that type 2 diabetes is an independent risk factor for osteoarthritis (OA). However, the mechanisms underlying the connection between both diseases remain unclear. Changes in the balance of hydrogen sulphide (H₂S) are thought to play an important role in the pathogenesis of diabetes and its complications, although its role is still controversial. In this study, we examined the modulation of H₂S levels in serum and chondrocytes from OA diabetic (DB) and non-diabetic (non-DB) patients and in cells under glucose stress, in order to elucidate whether impairment in H₂S-mediated signalling could participate in the onset of DB-related OA. Here, we identified a reduction in H₂S synthesis in the cartilage from OA-DB patients and in cells under glucose stress, which is associated with hyperglycaemia-mediated dysregulation of chondrocyte metabolism. In addition, our results indicate that H₂S is an inductor of the Nrf-2/HO-1 signalling pathway in cartilage, but is also a downstream target of Nrf-2 transcriptional activity. Thereby, impairment of the H₂S/Nrf-2 axis under glucose stress or DB triggers chondrocyte catabolic responses, favouring the disruption of cartilage homeostasis that characterizes OA pathology. Finally, our findings highlight the benefits of the use of exogeneous sources of H₂S in the treatment of DB-OA patients, and warrant future clinical studies.This research was funded by grant PI19/01206 from the Fondo de Investigación Sanitaria, integrated in the National Plan for Scientific Program, Development, and Technological Innovation 2013–2016 and funded by the Instituto de Salud Carlos III (ISCIII)-General Subdirection of Assessment and Promotion of Research-European Regional Development Fund (FEDER) “A way of making Europe”, and also by grants ED431B 2020/55 (Grupos con Potencial de Crecemento 2020) and IN607A 2021/7 (Grupos de Referencia Competitiva) from Xunta de Galicia. The study was also supported by the Biomedical Research Network Centre (CIBER), an initiative of ISCIII. C.V.-G. thanks Xunta de Galicia for his postdoctoral contract (grant number ED481D 2017/023)Xunta de Galicia; ED431B 2020/55Xunta de Galicia; IN607A 2021/7Xunta de Galicia; ED481D 2017/02

Search for Specific Biomarkers of IFNβ Bioactivity in Patients with Multiple Sclerosis

Myxovirus A (MxA), a protein encoded by the MX1 gene with antiviral activity, has proven to be a sensitive measure of IFNβ bioactivity in multiple sclerosis (MS). However, the use of MxA as a biomarker of IFNβ bioactivity has been criticized for the lack of evidence of its role on disease pathogenesis and the clinical response to IFNβ. Here, we aimed to identify specific biomarkers of IFNβ bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB) to IFNβ at 12 and/or 24 months of treatment and patients who remained NAB negative. Nine genes followed patterns in gene expression over time similar to the MX1, which was considered the gold standard gene, and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments in PBMC from healthy controls revealed specific induction of selected biomarkers by IFNβ but not IFNγ, and several markers, in particular USP18 and HERC5, were shown to be significantly induced at lower IFNβ concentrations and more selective than the MX1 as biomarkers of IFNβ bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p = 0.0004). We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFNβ bioactivity, and to further explore their implication in MS pathogenesis

Informe de resultados de la campaña `Maurit-0911'. Estudio de los ecosistemas de la plataforma y margen contiental de Mauritania

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Hydrozoans from Mauritanian deep waters

During the four Maurit surveys carried out annually from 2007 to 2010, 342 trawl stations were sampled off the Mauritanian coast between 80 and 2000-m depth. Hydroids were captured at 174 stations, totalling 6169 colonies belonging to 63 species and 19 families . Most of the species were Leptothecata and only seven belonged to Anthoathecata . Thirty-two of the 63 species are new records for Mauritania. Plumulariidae showed the highest species richness (8 species), followed by Sertulariidae and Campanulariidae (7 species), Lafoeidae , Haleciidae and Aglopheniidae (6 species). The most abundant were Sertulariidae , followed by Aglaopheniidae, Plumulariidae, Campanulariidae, Halopterididae and Haleciidae . The ability of hydroids to colonize Mauritanian soft bottom s was driven by hydrorhizal modifications for anchoring the colony to the sediment and by epizoism on 11 invertebrate groups. Families whose species developed both strategies and those which were typically epibionts on hydroids were the most frequent and abundant. Most of the species were eurybathic (58 species), with four species recorded only in the coastal realm, 18 exclusively in the deep benthic realm and 41 in both realms. Therefore, overall hydroid diversity was highest in the deep benthic realm . Biogeographical components included two main groups: species with a wide distribution (59%) and species of Atlantic distribution (41%); our results also emphasize the similarity between the Mauritanian hydroid fauna and the Atlantic-Mediterranean region. Only one species, Hydractinia multitentaculata (Millard 1975), has West African distribution. No endemic species were reported

A new species of Cuspidaria Nardo, 1840 (Mollusca: Bivalvia) in Mauritanian deep waters

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