Search

Chronic inflammatory diseases comprise complex interactions between professional immune and resident tissue cell lineages. Common etiopathogenic pathways are proposed across diseases including shared genetic and epigenetic factors, upon which various [...]

Introduction Hospitalization is associated with acute changes in sarcopenia status in older people, but the influencing factors are not fully understood. Pre-admission care dependency level as a risk factor has not yet been investigated. Objective Evaluate if pre-admission care dependency level is an independent predictor of sarcopenia changes following hospitalization. Setting and subjects Data came from the Sarcopenia 9+ EAMA Project, a European prospective multi-centre study. For this study, 227 hospitalised older people were included from four different hospitals in Belgium, Spain and Poland, between 18 February 2019 and 5 September 2020. Methods Sarcopenia status at admission and discharge were calculated using a combined score (desirability value) based on muscle mass (calf circumference), strength (grip) and function (walking speed). Ratio of admission to discharge status was the outcome (desirability ratio; 1.00 meaning no difference). Predictor variable was the pre-admission care dependency level, classified into three groups: independent older people living at home, dependent older people living at home and older people living in a care home. Linear regression models were applied, considering potential confounders. Results Mean desirability ratio for dependent older people living at home ('middle dependent group') was lower (0.89) compared to independent older people (0.98; regression coefficient −0.09 [95% CI −0.16, −0.02]) and care home patients (1.05; −0.16 [95% CI −0.01, −0.31]). Adjusting for potential confounders or using another statistical approach did not affect the main results. Conclusion Dependent older people living at home were at higher risk of deterioration in sarcopenia status following hospitalization. In-depth studies investigating causes and potential interventions of these findings are needed. [ABSTRACT FROM AUTHOR]

Abstract Background Immunological and genetic findings implicate Th17 effector cytokines in the pathogenesis of inflammatory bowel disease (IBD). Expression of Th17 pathway-associated genes is mainly studied in colonic disease. The present study assessed the mRNA expression levels of Th17 effector cytokines (IL17A, IL17F, IL21, IL22 and IL26) and genes involved in differentiation (IL6, IL1B, TGFB1, IL23A and STAT3) and recruitment of Th17 cells (CCR6 and CCL20) by quantitative real-time PCR analysis of colonic and ileal biopsies from 22 healthy control subjects, 26 patients with Crohn's disease (CD) and 12 patients with ulcerative colitis (UC). Inflammation was quantified by measuring expression of the inflammatory mediators IL8 and TNF. Results Evaluation of mRNA expression levels in colonic and ileal control samples revealed that TNF, TGFB1, STAT3 and CCR6 were expressed at higher levels in the ileum than in the colon. Expression of all the Th17 pathway-associated genes was increased in inflamed colonic samples. The increased expression of these genes was predominantly observed in samples from UC patients and was associated with more intense inflammation. Although increased expression of IL17A, IL17F, IL21 and IL26 was detected in inflamed ileal samples, expression of the indispensable Th17 cell differentiation factors TGFB1 and IL23A, the signaling molecule STAT3 and the Th17 recruitment factors CCR6 and CCL20 were unchanged. Conclusions Our findings suggest that immune regulation is different in colonic and ileal disease, which might have important consequences for therapeutic intervention.

Objectives: Tricalcium silicate (TCS)–based biomaterials induce differentiation of human dental pulp cells (hDPCs) into odontoblasts/osteoblasts, which is regulated by the interplay between various intracellular pathways and their resultant secretome. The aim of this study was to compare the transcriptome-wide effects by next-generation RNA sequencing of custom-prepared hDPCs stimulated with TCS-based biomaterials: ProRoot white MTA (WMTA) (Dentsply, Tulsa; Tulsa, OK) and Biodentine (Septodont, Saint Maur des Fosses, France). Methods: Self-isolated hDPCs were seeded in a 6-well plate at a density of 5 × 105 cells per well. ProRoot white MTA and Biodentine were then placed in transwell inserts with a pore size of 0.4 μm and inserted in the well plate. RNA sequencing was performed after 3 and 7 days treatment. For post-validation, RT-PCR analyses were done on some of the RNA samples used for RNA sequencing. Results: Our RNA sequencing results for the first time identified 7533 differentially expressed genes (DEGs) between different treatments and the number of DEGs in Biodentine was higher than ProRoot WMTA at both 3 and 7 days. Despite their differential gene expression, both the TCS-based biomaterial treatments showed gene expressions mainly involved in odontoblast differentiation, angiogenesis, neurogenesis, dentinogenesis, and tooth mineralization. Conclusions: The results of the present study illustrate that several important signalling pathways are induced by hDPCs stimulated with TCS-based biomaterials. Clinical relevance: The differential expression of the genes associated with odontogenesis, angiogenesis, neurogenesis, dentinogenesis, and mineralization may affect the prognosis of teeth treated with Biodentine or ProRoot white MTA. [ABSTRACT FROM AUTHOR]

Calcium (Ca2+) signalling plays an indispensable role in dental pulp and dentin regeneration, but the Ca2+ responses of human dental pulp stem cells (hDPSCs) stimulated with tricalcium silicate-based (TCS-based) dental biomaterials remains largely unexplored. The objective of the present study was to identify and correlate extracellular Ca2+ concentration, intracellular Ca2+ dynamics, pH, cytotoxicity, gene expression and mineralization ability of human dental pulp stem cells (hDPSCs) stimulated with two different TCS-based biomaterials: Biodentine and ProRoot white MTA. The hDPSCs were exposed to the biomaterials, brought in contact with the overlaying medium, with subsequent measurements of extracellular Ca2+ and pH, and intracellular Ca2+ changes. Messenger RNA expression (BGLAP, TGF-β, MMP1 and BMP2), cytotoxicity (MTT and TUNEL) and mineralization potential (Alizarin red and Von Kossa staining) were then evaluated. Biodentine released significantly more Ca2+ in the α-MEM medium than ProRoot WMTA but this had no cytotoxic impact on hDPSCs. The larger Biodentine-linked Ca2+ release resulted in altered intracellular Ca2+ dynamics, which attained a higher maximum amplitude, faster rise time and increased area under the curve of the Ca2+ changes compared to ProRoot WMTA. Experiments with intracellular Ca2+ chelation, demonstrated that the biomaterial-triggered Ca2+ dynamics affected stem cell-related gene expression, cellular differentiation and mineralization potential. In conclusion, biomaterial-specific Ca2+ dynamics in hDPSCs determine differentiation and mineralization outcomes, with increased Ca2+ dynamics enhancing mineralization. [ABSTRACT FROM AUTHOR]

Objectives: To assess axial involvement on MRI in early peripheral spondyloarthritis (pSpA) and to evaluate whether axial inflammation predicts relapse on treatment withdrawal.Methods: Fifty-six patients with early, active, newly diagnosed pSpA underwent MRI of the sacroiliac joints (SIJs) and spine prior to golimumab initiation. At sustained clinical remission of pSpA, treatment was withdrawn and a second MRI was performed. Bone marrow oedema (BME) was scored by three readers according to the Spondyloarthritis Research Consortium of Canada (SPARCC) method. Scores were compared with an axial spondyloarthritis cohort (Belgian Arthritis and Spondylitis cohort). Structural lesions were assessed using a similar method. Furthermore, fulfilment of the Assessment of Spondyloarthritis International Society (ASAS) definition of a positive MRI for sacroiliitis was assessed. Spinal images were evaluated for BME and structural lesions using the Canada-Denmark MRI spine scoring system by two readers.Results: Thirty-six per cent showed SIJ BME at baseline, all fulfilling the ASAS definition of sacroiliitis. No association with back pain was found. Twenty-one per cent displayed SIJ structural lesions. Spinal BME was limited: the median inflammation scores were low and no patients had ≥5 inflammatory corner lesions. On clinical remission, a significant decrease in SIJ SPARCC scores was detected. On clinical remission, no significant differences in SIJ SPARCC scores were noted between patients relapsing and those maintaining remission after treatment discontinuation.Conclusion: In patients with early pSpA, a surprisingly high prevalence of sacroiliitis on MRI was observed; SPARCC scores decreased significantly on tumour necrosis factor inhibition. Residual inflammation on MRI was not predictive of relapse of peripheral manifestations. No relevant inflammatory spinal involvement was detected. Collectively, our findings suggest a higher inflammatory burden in patients with early pSpA than anticipated. [ABSTRACT FROM AUTHOR]