SUMMARYPTX3 is a secreted molecule which consists of a C-terminal domain similar to classical pentraxins (e.g. C-reactive protein (CRP)) and of an unrelated N-terminal domain. Unlike the classical pentraxins, the long pentraxin PTX3 is expressed in response to IL-1b and tumour necrosis factor-alpha (TNF-a), but not to IL-6, in various cell types. The present study was designed to investigate the expression of PTX3 in RA. Dissociated RA and osteoarthritis (OA) type B synoviocytes were cultured in the presence and in the absence of inflammatory cytokines. PTX3 mRNA expression in synoviocytes was evaluated by Northern analysis. PTX3 protein levels in synovial cell cultures and synovial fluid were estimated by ELISA, and PTX3 distribution in synovial tissues by immunohistochemical techniques. OA synoviocytes were induced to express high levels of PTX3 mRNA by TNF-a, but not by other cytokines including IL-1b and IL-6. RA synoviocytes, unlike OA synoviocytes, constitutively expressed high levels of PTX3 in the absence of deliberate stimulation. The constitutive expression of PTX3 in RA synoviocytes was not modified by anti-TNF-a antibodies, IL-1 receptor antagonist or a combination of the two agents. In contrast, interferon-gamma and transforming growth factor-beta inhibited PTX3 constitutive expression in RA synoviocytes. The joint fluid from RA patients contained higher levels of immunoreactive PTX3 than controls and the synovial tissue contained endothelial cells and synoviocytes positive for PTX3 by immunohistochemistry. In conclusion, PTX3 may play a role in inflammatory circuits of RA, and its relevance as a marker of disease activity deserves further study.
Highlights
Tocilizumab (TCZ) is currently being tested in COVID‐19‐induced cytokine storm.
COVID-19 patients responding to TCZ have higher post-treatment levels of circulating miR-146a.
Low levels of miR-146a are associated with death in COVID-19 patients not responding to TCZ.
MicroRNAs can represent biomarkers of response to anti-inflammatory interventions in COVID-19.
The potential impact of biofilm on healing in acute and chronic wounds is one of the most controversial current issues in wound care. A significant amount of laboratory-based research has been carried out on this topic, however, in 2013 the European Wound Management Association (EWMA) pointed out the lack of guidance for managing biofilms in clinical practice and solicited the need for guidelines and further clinical research. In response to this challenge, the Italian Nursing Wound Healing Society (AISLeC) initiated a project which aimed to achieve consensus among a multidisciplinary and multiprofessional international panel of experts to identify what could be considered part of 'good clinical practice' with respect to the recognition and management of biofilms in acute and chronic wounds. The group followed a systematic approach, developed by the GRADE working group, to define relevant questions and clinical recommendations raised in clinical practice. An independent librarian retrieved and screened approximately 2000 pertinent published papers to produce tables of levels of evidence. After a smaller focus group had a multistep structured discussion, and a formal voting process had been completed, ten therapeutic interventions were identified as being strongly recommendable for clinical practice, while another four recommendations were graded as being 'weak'. The panel subsequently formulated a preliminary statement (although with a weak grade of agreement): 'provided that other causes that prevent optimal wound healing have been ruled out, chronic wounds are chronically infected'. All members of the panel agreed that there is a paucity of reliable, well-conducted clinical trials which have produced clear evidence related to the effects of biofilm presence. In the meantime it was agreed that expert-based guidelines were needed to be developed for the recognition and management of biofilms in wounds and for the best design of future clinical trials. This is a fundamental and urgent task for both laboratory-based scientists and clinicians.
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