Analysis of the Nutritional Composition of Ready-to-Use Meat Alternatives in Belgium.

Background: The interest in meat alternatives has increased over the years as people embrace more varied food choices because of different reasons. This study aims to analyse the nutritional composition of ready-to-use meat alternatives and compare them with meat (products).

Methods: Nutritional composition values were collected in 2022 of all ready-to-use meat alternatives in Belgian supermarkets, as well as their animal-based counterparts.

Integrated safety analysis of filgotinib in patients with moderate-to-severe rheumatoid arthritis over a treatment duration of up to 8.3 years.

Objectives: To update the long-term safety profile of filgotinib, a Janus kinase-1 preferential inhibitor, in patients with moderate-to-severe rheumatoid arthritis.

Methods: Data from seven trials were integrated (NCT01888874, NCT01894516, NCT02889796, NCT02873936, NCT02886728, NCT02065700 and NCT03025308). Patients received once-daily filgotinib 100 mg or 200 mg.

What benefit-risk trade-offs are acceptable to rheumatoid arthritis patients during treatment selection? Evidence from a multicountry choice experiment.

Objective: Understanding preferences of patients with rheumatoid arthritis (RA) can facilitate tailored patient-centric care. This study elicited trade-offs that patients with RA were willing to make during treatment selection.

Methods: Patients with RA completed an online discrete choice experiment, consisting of a series of choices between hypothetical treatments.

Impact of COVID-19 pandemic on the management of patients with RA: a survey of rheumatologists in six European countries.

Objective: We aimed to describe, from the perspective of rheumatologists in Europe, how the coronavirus disease 2019 (COVID-19) pandemic has impacted their management of people with RA and the continuing medical education of physicians.

Methods: Rheumatologists participating in the Adelphi RA Disease Specific Programme in six European countries were contacted in August and September 2020 for a telephone survey. Rheumatologists were asked seven attitudinal questions on changes to patient management, prescription behaviour and continuing education owing to COVID-19.

Treat-to-target in rheumatoid arthritis: a real-world study of the application and impact of treat-to-target within the wider context of patient management, patient centricity and advanced therapy use in Europe.

Background: While treat-to-target (T2T) is endorsed for the management of rheumatoid arthritis (RA), data on the degree of implementation in clinical practice are limited. This study investigated the use of T2T for RA in a real-world setting across Europe.

Methods: The Adelphi RA Disease-Specific Programme was a point-in-time survey of rheumatologists and their consulting patients with RA conducted between January and October 2020 in Belgium, France, Germany, Italy, Spain and the UK.

Adjustments in Food Choices and Physical Activity during Lockdown by Flemish Adults.

Background: On Wednesday 18/03/2020 Belgium was placed in lockdown in order to curb the spread of COVID-19. Lockdown can lead to loneliness, boredom, anger, anxiety and depression, which in turn have an influence on food choices and physical activity (PA). This study aims to map the adjustments in food choices and PA by Flemish adults during lockdown.

Endothelial Nitric Oxide Synthase Prevents Heparanase Induction and the Development of Proteinuria.

Endothelial nitric oxide synthase (eNOS) deficiency exacerbates proteinuria and renal injury in several glomerular diseases, but the underlying mechanism is not fully understood. We recently showed that heparanase is essential for the development of experimental diabetic nephropathy and glomerulonephritis, and hypothesize that heparanase expression is regulated by eNOS. Here, we demonstrate that induction of adriamycin nephropathy (AN) in C57BL/6 eNOS-deficient mice leads to an increased glomerular heparanase expression accompanied with overt proteinuria, which was not observed in the AN-resistant wild type counterpart.

Design of an Optimized Wilms' Tumor 1 (WT1) mRNA Construct for Enhanced WT1 Expression and Improved Immunogenicity In Vitro and In Vivo.

Tumor antigen-encoding mRNA for dendritic cell (DC)-based vaccination has gained increasing popularity in recent years. Within this context, two main strategies have entered the clinical trial stage: the use of mRNA for ex vivo antigen loading of DCs and the direct application of mRNA as a source of antigen for DCs in vivo. DCs transfected with mRNA-encoding Wilms' tumor 1 (WT1) protein have shown promising clinical results.

Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis.

Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis.

Class II HDAC inhibition hampers hepatic stellate cell activation by induction of microRNA-29.

Background: The conversion of a quiescent vitamin A storing hepatic stellate cell (HSC) to a matrix producing, contractile myofibroblast-like activated HSC is a key event in the onset of liver disease following injury of any aetiology. Previous studies have shown that class I histone deacetylases (HDACs) are involved in the phenotypical changes occurring during stellate cell activation in liver and pancreas.

Aims: In the current study we investigate the role of class II HDACs during HSC activation.

HDAC inhibitors in experimental liver and kidney fibrosis.

Histone deacetylase (HDAC) inhibitors have been extensively studied in experimental models of cancer, where their inhibition of deacetylation has been proven to regulate cell survival, proliferation, differentiation and apoptosis. This in turn has led to the use of a variety of HDAC inhibitors in clinical trials. In recent years the applicability of HDAC inhibitors in other areas of disease has been explored, including the treatment of fibrotic disorders.

Valproic acid attenuates proteinuria and kidney injury.

Inhibitors of histone deacetylase (HDAC) have anti-inflammatory and antifibrotic effects in several organs and tissues, but their effect on the progression of renal disease is unknown. Here, we studied the effect of valproic acid in adriamycin-induced nephropathy in mice. Administration of valproic acid before kidney injury prevented the development of proteinuria and the onset of glomerulosclerosis.

Galactose-modified iNKT cell agonists stabilized by an induced fit of CD1d prevent tumour metastasis.

Invariant natural killer T (iNKT) cells are known to have marked immunomodulatory capacity due to their ability to produce copious amounts of effector cytokines. Here, we report the structure and function of a novel class of aromatic α-galactosylceramide structurally related glycolipids with marked Th1 bias in both mice and men, leading to superior tumour protection in vivo. The strength of the Th1 response correlates well with enhanced lipid binding to CD1d as a result of an induced fit mechanism that binds the aromatic substitution as a third anchor, in addition to the two lipid chains.

An anti-inflammatory selective glucocorticoid receptor modulator preserves osteoblast differentiation.

Glucocorticoids (GCs) are in widespread use to treat inflammatory bone diseases, such as rheumatoid arthritis (RA). Their anti-inflammatory efficacy, however, is accompanied by deleterious effects on bone, leading to GC-induced osteoporosis (GIO). These effects include up-regulation of the receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) ratio to promote bone-resorbing osteoclasts and include inhibition of bone-forming osteoblasts.

Invariant natural killer T cells are natural regulators of murine spondylarthritis.

Objective: To investigate the role of invariant natural killer T (iNKT) cells in TNF(DeltaARE/+) mice, an animal model of spondylarthritis (SpA) with both gut and joint inflammation.

Methods: The frequency and activation of iNKT cells were analyzed on mononuclear cells from the lymph nodes and livers of mice, using flow cytometry with alpha-galactosylceramide/CD1d tetramers and quantitative polymerase chain reaction for the invariant V(alpha)14-J(alpha)18 rearrangement. Bone marrow-derived dendritic cells (DCs) were obtained by expansion of primary cells with granulocyte-macrophage colony-stimulating factor followed by coculture with iNKT cell hybridomas, and interleukin-2 release into the cocultures was then measured by enzyme-linked immunosorbent assay (ELISA).

Cutting edge: the chemokine receptor CXCR3 retains invariant NK T cells in the thymus.

The current model used to define T cell export from the thymus suggests that emigrating lymphocytes seed the peripheral organs as functionally mature cells. This model holds true for the majority of T cells exported from the thymus with the exception of invariant NK T (iNKT) cells. iNKT cells undergo lineage expansion after positive selection and acquire NK receptor expression once fully mature; yet, the majority of mature iNKT cells are retained in the thymus by an as of yet unidentified mechanism.

Application of a new anti-zearalenone monoclonal antibody in different immunoassay formats.

Monoclonal antibodies against zearalenone (ZEA) were raised in mice according to the hybridoma technology and applied in different immunochemical techniques. More specifically, three formats based on the competitive direct enzyme immunoassay principle were developed: an enzyme-linked immunosorbent assay (ELISA), a flow-through gel-based immunoassay column and a flow-through membrane-based immunoassay. In ELISA, the 50% inhibitory concentration (IC50) was 0.

A plant-derived glucocorticoid receptor modulator attenuates inflammation without provoking ligand-induced resistance.

Background: Acquired resistance to glucocorticoids constitutes a major clinical challenge, often overlooked in the search for improved alternatives to classic steroids. We sought to unravel how two glucocorticoid receptor-activating compounds, dexamethasone and Compound A, influence glucocorticoid receptor levels and how this can be correlated to their gene regulatory potential.

Methods: Compound A and dexamethasone were applied in a short-term and long-term treatment protocol.

The synthesis and in vivo evaluation of 2',2'-difluoro KRN7000.

The synthesis of 2',2'-difluoro KRN7000 is described. In vivo evaluation demonstrates that this fluorinated glycolipid induces CD1d-dependent TCR activation of NKT cells, with a bias towards Th2 cytokine production.

Synthesis and in vivo evaluation of 4-deoxy-4,4-difluoro-KRN7000.

The synthesis of 4-deoxy-4,4-difluoro-KRN7000 starting from phytosphingosine is described. Key steps include a regioselective benzylation of azidophytosphingosine and a deoxofluor-mediated fluorination of the corresponding 4-ketone. This fluorination failed completely when the adjacent 3-OH was protected as benzyl ether but proceeded well when a benzoyl group was used.

Reversible changes in serum immunoglobulin galactosylation during the immune response and treatment of inflammatory autoimmune arthritis.

Objectives: Improved DNA sequencer-aided fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) technology was used to monitor the changes in the galactosylation status of serum immunoglobulins during the immune response and therapy of autoimmune arthritis.

Methods: Collagen-induced arthritis (CIA) was induced in susceptible DBA/1 mice and the undergalactosylation status (UGS) of serum immunoglobulins was determined using the improved DSA-FACE technology. Prophylactic intravenous tolerisation with type II collagen as well as semitherapeutic treatment with dexamethasone (DEX) were performed and UGS was analysed.

CRBP-I in the renal tubulointerstitial compartment of healthy rats and rats with renal fibrosis.

Background: Cellular retinol-binding protein I (CRBP-I), a member of the intracellular lipid-binding protein (iLBP) superfamily, is a specific marker of quiescent stellate cells in the healthy human liver. In the diseased fibrotic/cirrhotic liver, portal and septal myofibroblasts acquire CRBP-I expression, while activated hepatic stellate cells maintain their CRBP-I expression. Here, we investigate the distribution of CRBP-I in the renal cortex of healthy rats and rats with renal fibrosis.

Synthesis and in vitro evaluation of alpha-GalCer epimers.

alpha-GalCer (also known as KRN7000) is an immunomodulatory glycolipid that is known to potently activate invariant natural killer T (NKT) cells upon CD1d-mediated stimulation. Because Th1 and Th2 cytokines, which are released after alpha-GalCer presentation, antagonize each other's effects, alpha-GalCer analogues that induce a biased Th1/Th2 response are highly awaited. In this context, we report the synthesis and in vitro evaluation of alpha-Gal-D-xylo-Cer and two alpha-Gal-L-lyxo-Cer analogues, one with the natural acyl chain, the other with a truncated chain.