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Background: Rheumatoid arthritis (RA) significantly increases the overall risk of cardiovascular disease (CVD). In addition to conventional risk factors, the inflammatory activity of the disease itself and medications that promote atherosclerosis contribute to an even greater risk. In this study, we performed metabolomic analysis in RA patients, both on and off disease-modifying anti-rheumatic drug (DMARD) therapy, with the aim of identifying new candidates for more sophisticated cardiovascular risk (CVR) assessment., Methods: This is an observational, cross-sectional investigation that included patients with established RA. DMARD therapy, if prescribed, consisted of methotrexate (MTX) alone or in combination with other conventional disease-modifying anti-rheumatic drugs (cDMARDs) or biologic disease-modifying anti-rheumatic drugs (bDMARDs), or other cDMARDs or bDMARDs without MTX, respectively. Metabolomic profiling was conducted using a Bruker AVANCE NEO 600 MHz nuclear magnetic resonance (NMR) spectrometer. The spectra obtained were Fourier transformed using TopSpin software (version 4.0, Bruker Biospin, Germany). All spectra were automatically phased and subjected to baseline correction. Subsequently, the spectra were analyzed using the proprietary Profiler software (version 1.4_Blood, lifespin GmbH, Germany), and a quantitative metabolite list was generated., Results: In total, 200 patients were included in the study, 54 subjects were not receiving any DMARDs (n = 47 untreated at the time of inclusion, n = 7 with established disease but not receiving DMARD therapy), and 146 were receiving DMARD treatment. No metabolic differences were found in relation to drug therapy or RA activity. The following CVR factors were associated with significant metabolic abnormalities: distress, arterial hypertension, diabetes mellitus and an average higher Framingham score. Distressed individuals showed abnormalities in histidine metabolism., Conclusions: Our findings have aided in the identification of potential surrogate markers for assessing the burden of CVD in individuals with RA. Histidine may be of particular diagnostic importance in CVR assessment in RA., Competing Interests: Steffen Heelemann and Selina Strathmeyer are employees at lifespin., (Copyright 2025, Claus et al.)

Objective: To conduct a metabolomics analysis in patients with spondyloarthritis (SpA) and compare results with those from healthy controls. The overall goal was to identify small-molecule substances that may have potential pathogenic and diagnostic significance in SpA., Methods: This was an observational, cross-sectional, single-centre study that included patients with axial (ankylosing spondylitis [AS]), peripheral (psoriatic arthritis [PsA]) and healthy controls., Results: The study included 50 patients with AS, 50 patients with PsA, and 164 controls. When compared with healthy controls, patients with SpA showed significant differences in 35 metabolites, primarily associated with amino acid and lipid metabolism. However, only two differences were found between the AS and PsA cohorts (glucose and glycerol)., Conclusions: Our data suggest that patients with SpA exhibit significant disruptions in amino acid and lipid metabolism. The large number of identified metabolites offers promising opportunities, both for discovering new SpA biomarkers and for gaining a deeper understanding of the pathophysiology of these chronic inflammatory diseases., Competing Interests: Declaration of conflicting interestThe authors declare there are no conflicts of interest. Selina Strathmeyer and Steffen Heelemann are employees of lifespin GmbH.

Background: Comprehensive characterization of the metabolome in cerebrospinal fluid (CSF) and serum by Nuclear Magnetic Resonance (NMR) spectroscopy may identify biomarkers and contribute to the understanding of the pathophysiology of neurological diseases., Methods: Metabolites were determined by NMR spectroscopy in stored CSF/serum samples of 20 patients with Parkinson's disease, 25 patients with other neuro-degenerative diseases, 22 patients with cerebral ischemia, 48 patients with multiple sclerosis, and 58 control patients with normal CSF findings. The data set was analysed using descriptive and multivariate statistics, as well as machine learning models., Results: CSF glucose and lactic acid measured by NMR spectroscopy and routine clinical chemistry showed a strong correlation between both methods (glucose, R 2  = 0.87, n = 173; lactic acid, R 2  = 0.74, n = 173). NMR spectroscopy detected a total of 99 metabolites; 51 in both, CSF and serum, 16 in CSF only, and 32 in serum only. CSF concentrations of some metabolites increased with age and/or decreasing blood-brain-barrier function. Metabolite detection rates were overall similar among the different disease groups. However, in two-group comparisons, absolute metabolite levels in CSF and serum discriminated between multiple sclerosis and neurodegenerative diseases (area under the curve (AUC) = 0.96), multiple sclerosis and Parkinson's disease (AUC = 0.89), and Parkinson's disease and control patients (AUC = 0.91), as demonstrated by random forest statistical models. Orthogonal partial least square discriminant analysis using absolute metabolite levels in CSF and serum furthermore permitted separation of Parkinson's disease and neurodegenerative diseases. CSF propionic acid levels were about fourfold lower in Parkinson's disease as compared to neurodegenerative diseases., Conclusions: These findings outline the landscape of the CSF and serum metabolome in different categories of neurological diseases and identify age and blood-brain-barrier function as relevant co-factors for CSF levels of certain metabolites. Metabolome profiles as determined by NMR spectroscopy may potentially aid in differentiating groups of patients with different neurological diseases, including clinically meaningful differentiations, such as Parkinson's disease from other neurodegenerative diseases., (© 2024. The Author(s).)

Fermentable carbohydrates are gaining interest in the field of human nutrition because of their benefits in obesity-related comorbidities. The aim of this study was to investigate the influence of fermentable carbohydrates, such as pectin and inulin, in an atherogenic diet on metabolic responses and plaque formation in coronary arteries using a Saddleback pig model. Forty-eight healthy pigs aged five months were divided into four feeding groups (n = 10) and one baseline group (n = 8). Three feeding groups received an atherogenic diet (38% crisps, 10% palm fat, and 2% sugar with or without supplementation of 5% pectin or inulin), and one group received a conventional diet over 15 weeks. Feed intake, weight gain, body condition score, and back fat thickness were monitored regularly. Blood and fecal samples were collected monthly to assess the metabolites associated with high cardiovascular risk and fat content, respectively. At the end of 15 weeks, the coronary arteries of the pigs were analyzed for atherosclerotic plaque formation. Independent of supplementation, significant changes were observed in lipid metabolism, such as an increase in triglycerides, bile acids, and cholesterol in serum, in all groups fed atherogenic diets in comparison to the conventional group. Serum metabolome analysis showed differentiation of the feeding groups by diet (atherogenic versus conventional diet) but not by supplementation with pectin or inulin. Cardiovascular lesions were found in all feeding groups and in the baseline group. Supplementation of pectin or inulin in the atherogenic diet had no significant impact on cardiovascular lesion size. Saddleback pigs can develop naturally occurring plaques in coronary arteries. Therefore, this pig model offers potential for further research on the effects of dietary intervention on obesity-related comorbidities, such as cardiovascular lesions, in humans., Competing Interests: The authors have declared that no competing interests exist.

Equine hepacivirus (EqHV) is the closest known genetic homologue of hepatitis C virus. An effective prophylactic vaccine is currently not available for either of these hepaciviruses. The equine as potential surrogate model for hepacivirus vaccine studies was investigated, while equine host responses following vaccination with EqHV E2 recombinant protein and subsequent EqHV inoculation were elucidated. Four ponies received prime and booster vaccinations (recombinant protein, adjuvant) four weeks apart (day -55 and -27). Two control ponies received adjuvant only. Ponies were inoculated with EqHV RNA-positive plasma on day 0. Blood samples and liver biopsies were collected over 26 weeks (day -70 to +112). Serum analyses included detection of EqHV RNA, isotypes of E2-specific immunoglobulin G (IgG), nonstructural protein 3-specific IgG, haematology, serum biochemistry, and metabolomics. Liver tissue analyses included EqHV RNA detection, RNA sequencing, histopathology, immunohistochemistry, and fluorescent in situ hybridization. Al-though vaccination did not result in complete protective immunity against experimental EqHV inoculation, the majority of vaccinated ponies cleared the serum EqHV RNA earlier than the control ponies. The majority of vaccinated ponies appeared to recover from the EqHV-associated liver insult earlier than the control ponies. The equine model shows promise as a surrogate model for future hepacivirus vaccine research.