Search

IntroductionSystemic sclerosis (SSc) is an autoimmune disease characterized by antinuclear antibody production, which has been linked to an excess of apoptotic cells, normally eliminated by macrophages through efferocytosis. Additionally, circulating levels of CXCL4, a novel SSc biomarker, correlate with more severe fibrotic manifestations of the disease. Considering the defective efferocytosis of macrophages in SSc and the CXCL4-related M4 macrophage phenotype, we hypothesized that CXCL4 could be involved in the alteration of phagocytic functions of macrophages in SSc, including LC3-associated phagocytosis (LAP), another phagocytic process requiring autophagy proteins and contributing to immune silencing.MethodsIn this study, CXCL4 levels were measured by ELISA in vitro in the serum of SSc patients, and also in vivo in the serum and lungs of C57BL/6J SSc mice induced by intradermal injections of hypochloric acid (HOCl) or Bleomycin (BLM), with evaluation of M4 markers. Circulating monocytes from healthy donors were also differentiated in vitro into M4 monocytes-derived macrophages (MDMs) in the presence of recombinant CXCL4. In M4-MDMs, phagocytosis of fluorescent beads and expression level of efferocytic receptors were evaluated by flow cytometry in vitro, while efferocytosis of pHrodo-stained apoptotic Jurkat cells was evaluated by real-time fluorescence microscopy. LAP quantification was made by fluorescence microscopy in M4-MDMs exposed to IgG-coated beads as well as apoptotic Jurkat cells.ResultsOur results demonstrated that efferocytosis was significantly reduced in M0-MDMs from healthy donors exposed to the CXCL4-rich plasma of SSc patients. In vivo, CXCL4 expression was increased in the lungs of both SSc-mouse models, along with elevated M4 markers, while efferocytosis of BLM-mice alveolar macrophages was decreased. In vitro, M4-MDMs exhibited reduced efferocytosis compared to M0-MDMs, notably attributable to lower CD36 receptor expression and impaired phagocytosis capacities, despite enhanced LAP. Autophagic gene expression was increased both in vitro in SSc MDMs and in vivo in BLM mice, thus acting as a potential compensatory mechanism.DiscussionAltogether, our results support the role of CXCL4 on the impaired efferocytosis capacities of human macrophages from SSc patients and in SSc mice.

ABSTRACT: Vaccination is one of the most important control tools to reduce Salmonella in poultry production. In order for a live vaccine to be licensed for field use it should be provided with the detection methods to differentiate it from field strains. This paper aims to describe the validation of an alternative method for the differentiation of the Salmonella 441/014 vaccine strain from field strains, using a chromogenic Media, ASAP from bioMérieux. The ASAP-based differentiation method was compared with already authorized methods, namely the Anicon SE Kylt PCR DIVA 1 assay and Ceva S-Check Salmonella differentiation kit, following the ISO 16140-6:2019 validation method guidelines. A Generalised Linear Model was fitted to the data to determine the inclusivity and exclusivity of differentiation methods (PCR Kylt vs. S-Check vs. ASAPTM). Statistical differences were based on a P-value level of < 0.05 (SPSS Inc., Chicago, IL). In this study, we show that the ASAP media was able to differentiate Salmonella Enteritidis vaccine strains from field strains, obtaining 100% agreement between the three differentiation assays. This differentiation approach is quicker, easier to deploy and cheaper as compared to alternative methods.

Abstract Light pollution, by changing organisms’ behavior, affects locomotion, migration and can ultimately fragment the habitat. To investigate the effects of light pollution on habitat fragmentation, we conducted an experimental study on a nocturnal and photosensitive primate, the grey mouse lemur (Microcebus murinus). Twelve males were housed individually in an apparatus with two cages connected by two corridors, opaque and transparent. During 4 nights, the transparent corridor was illuminated by specific light intensities: 0 lx, 0.3 lx, 20 lx and 51.5 lx corresponding respectively to total darkness, full moon, minimal intensity recommended by the European standard EN-13201 on public lighting, and to light pollution recorded in an urban area. Each night, general activity, use of corridors and cage occupancy were recorded using an infrared camera. For the first time in a nocturnal primate, results demonstrate that light pollution changes the preference of use of corridors, modifies the locomotor pattern and limits the ability of animals to efficiently exploit their environment according to a light intensity-dependent relationship. However, results indicate that a dark corridor allows partial compensation partly preserving general activities. This study highlights the necessity to consider light pollution during the implementation of conservation plans and the relevance of nocturnal frames.

Background Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Cardiac involvement in SLE is rare but plays an important prognostic role. The degree of cardiac involvement according to SLE subsets defined by non-cardiac manifestations is unknown. The objective of this study was to identify differences in transthoracic echocardiography (TTE) parameters associated with different SLE subgroups.Methods One hundred eighty-one patients who fulfilled the 2019 American College of Rheumatology/EULAR classification criteria for SLE and underwent baseline TTE were included in this cross-sectional study. We defined four subsets of SLE based on the predominant clinical manifestations. A multivariate multinomial regression analysis was performed to determine whether TTE parameters differed between groups.Results Four clinical subsets were defined according to non-cardiac clinical manifestations: group A (n=37 patients) showed features of mixed connective tissue disease, group B (n=76 patients) had primarily cutaneous involvement, group C (n=18) exhibited prominent serositis and group D (n=50) had severe, multi-organ involvement, including notable renal disease. Forty TTE parameters were assessed between groups. Per multivariate multinomial regression analysis, there were statistically significant differences in early diastolic tricuspid annular velocity (RV-Ea, p

Trifluridine/tipiracil (FTD/TPI) is approved in third-line treatment of patients with advanced/metastatic gastric and gastroesophageal junction adenocarcinomas (aGA/GEJA). The association of oxaliplatin with FTD/TPI is promising and the combination of FTD/TPI + oxaliplatin + nivolumab has shown a predictable and manageable safety profile. The aim is to evaluate the efficacy and safety of FTD/TPI plus oxaliplatin with or without nivolumab in patients, with HER2 negative aGA/GEJA, unfit for triplet chemotherapy (TFOX/mFLOT regimen), in the first-line metastatic setting in comparison with the standard of care FOLFOX with or without nivolumab. This study is a prospective randomised, open label, comparative, multicentre, phase II trial designed to include 118 patients. The primary objective is to evaluate the superiority of FTD/TPI plus oxaliplatin with or without nivolumab over FOLFOX regimen with or without nivolumab in terms of PFS in a population of patients non candidate for triplet chemotherapy. Nivolumab will be used for patients whose tumour express PD-L1 with a CPS score ≥5. PRODIGE73-UCGI40-LOGICAN study will provide efficacy and safety data on the association of FTD/TPI plus oxaliplatin with or without nivolumab versus FOLFOX regimen with or without nivolumab in first-line palliative setting, in patients with aGA/GEJA (NCT05476796). [ABSTRACT FROM AUTHOR]