Ameliorative effects of the flavonoid fustin in a rat model of trinitrobenzensulfonic acid-induced colitis

Trinitrobenzene sulfonic acid (TNBS)-induced colitis is a widely used animal model that mimics the signs and symptoms of inflammatory bowel disease. Fustin is a flavonoid found in Cotinus coggygria. The aim of the present study was to investigate the effect of fustin isolated from Cotinus coggygria heartwood in a rat model of TNBS-induced colitis. In this experiment, 30 male Wistar rats were used, allocated to three groups: Control, TNBS and TNBS+F10. Colitis was induced by rectal application of TNBS. After the induction of colitis, fustin at a dose of 10 mg/kg was administered orally to TNBS+F10 group in the course of 8 days. Severity of colitis, oxidative stress and inflammation were assessed by macroscopic, histopathological, immunohistochemical and biochemical analyses. Rats from TNBS group demonstrated severe colonic damage. Fustin treatment ameliorated most of the macroscopic and some of the histopathological indices of colonic damage, and restored the activity of the endogenous antioxidant superoxide dismutase in tissue homogenate but did not affect the signs of inflammation measured by the activity of alkaline phosphatase in serum and tissue homogenate, as well as the expression of NF-kB in the colon. In conclusion, the ameliorative effects of fustin in the experimental TNBS-induced colitis might be the result of its antioxidant properties.International Conference: Kliment's Days 2023 - 60 years Faculty of Biology 09/11/2023 - 11/11/2023 Sofia, Bulgari

Effect of Aronia melanocarpa fruit juice on glucose tolerance, lipid metabolism, and obesity in a rat model of metabolic syndrome

Abstract Metabolic syndrome (MS) is a serious health condition. The purpose of this study was to investigate the effects of polyphenol-rich Aronia melanocarpa fruit juice (AMFJ) on glucose tolerance, triglyceride levels, and adipose tissue in rats with MS induced by high-fat high-fructose (HFHF) diet. Fifty rats were allocated in 5 groups: control, MS, MS+AMFJ2.5, MS+AMFJ5, and MS+AMFJ10. In the course of 10 weeks, the control group was on a regular rat diet while the other groups received HFHF diet. During the experiment, control and MS groups were treated daily orally with distilled water (10.0 mL kg−1) and the other three groups – with AMFJ at doses of 2.5, 5.0, and 10.0 mL kg−1, respectively. In MS rats, glucose intolerance, hypertriglyceridemia, visceral obesity, and increased adipocyte size were observed. In AMFJ-treated groups, the serum glucose and triglycerides, as well as visceral fat and adipocyte size decreased significantly and did not differ from those of the control group. AMFJ at doses 2.5 and 5.0 mL kg−1 showed an anti-apoptotic activity in adipocytes, while at the dose of 10 mL kg−1 a pro-apoptotic effect was detected. In conclusion, AMFJ could antagonise most of the negative consequences of HFHF diet on carbohydrate and lipid metabolism in a rat MS model

Serum contactin-1 as a biomarker of long-term disease progression in natalizumab-treated multiple sclerosis.

BACKGROUND: Natalizumab treatment provides a model for non-inflammation-induced disease progression in multiple sclerosis (MS). OBJECTIVE: To study serum contactin-1 (sCNTN1) as a novel biomarker for disease progression in natalizumab-treated relapsing-remitting MS (RRMS) patients. METHODS: Eighty-nine natalizumab-treated RRMS patients with minimum follow-up of 3 years were included. sCNTN1 was analyzed at baseline (before natalizumab initiation), 3, 12, 24 months (M) and last follow-up (median 5.2 years) and compared to 222 healthy controls (HC) and 15 primary progressive MS patients (PPMS). Results were compared between patients with progressive, stable, or improved disability according to EDSS-plus criteria. RESULTS: Median sCNTN1 levels (ng/mL,) in RRMS (baseline: 10.7, 3M: 9.7, 12M: 10.4, 24M: 10.8; last follow-up: 9.7) were significantly lower compared to HC (12.5; p ⩽ 0.001). It was observed that 48% of patients showed progression during follow-up, 11% improved, and 40% remained stable. sCNTN1 levels were significantly lower in progressors both at baseline and at 12M compared to non-progressors. A 1 ng/mL decrease in baseline sCNTN1 was consistent with an odds ratio of 1.23 (95% confidence interval 1.04-1.45) (p = 0.017) for progression during follow-up. CONCLUSION: Lower baseline sCNTN1 concentrations were associated with long-term disability progression during natalizumab treatment, making it a possible blood-based prognostic biomarker for RRMS

Antibody development and disease severity of COVID-19 in non-immunised patients with rheumatic immune-mediated inflammatory diseases: data from a prospective cohort study

Contains fulltext : 251778.pdf (Publisher’s version ) (Open Access)BACKGROUND: Research on the disease severity of COVID-19 in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) has been inconclusive, and long-term prospective data on the development of SARS-CoV-2 antibodies in these patients are lacking. METHODS: Adult patients with rheumatic IMIDs from the Amsterdam Rheumatology and Immunology Center, Amsterdam were invited to participate. All patients were asked to recruit their own sex-matched and age-matched control subject. Clinical data were collected via online questionnaires (at baseline, and after 1-4 and 5-9 months of follow-up). Serum samples were collected twice and analysed for the presence of SARS-CoV-2-specific antibodies. Subsequently, IgG titres were quantified in samples with a positive test result. FINDINGS: In total, 3080 consecutive patients and 1102 controls with comparable age and sex distribution were included for analyses. Patients were more frequently hospitalised compared with controls when infected with SARS-CoV-2; 7% vs 0.7% (adjusted OR: 7.33, 95% CI: 0.96 to 55.77). Only treatment with B-cell targeting therapy was independently associated with an increased risk of COVID-19-related hospitalisation (adjusted OR: 14.62, 95% CI: 2.31 to 92.39). IgG antibody titres were higher in hospitalised compared with non-hospitalised patients, and slowly declined with time in similar patterns for patients in all treatment subgroups and controls. INTERPRETATION: We observed that patients with rheumatic IMIDs, especially those treated with B-cell targeting therapy, were more likely to be hospitalised when infected with SARS-CoV-2. Treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and biological DMARDs other than B-cell targeting agents is unlikely to have negative effects on the development of long-lasting humoral immunity against SARS-CoV-2

Patient-reported daily functioning after SARS-CoV-2 vaccinations in autoimmune neuromuscular diseases

Background and purpose: There are concerns for safety regarding SARS-CoV-2 vaccines for patients with autoimmune neuromuscular disease. We compared daily functioning using disease-specific patient-reported outcome measures (PROMs) before and after SARS-CoV-2 vaccinations. Methods: In this substudy of a prospective observational cohort study (Target-to-B!), patients with myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and idiopathic inflammatory myopathy (IIM) vaccinated against SARS-CoV-2 were included. Surveys of daily functioning (Myasthenia Gravis Activities of Daily Living, Inflammatory Rasch-Built Overall Disability Scale, Multifocal Motor Neuropathy Rasch-Built Overall Disability Scale, and Health Assessment Questionnaire-Disability Index) were sent before first vaccination and every 60 days thereafter for up to 12 months. Regression models were constructed to assess differences in PROM scores related to vaccination, compared to scores unrelated to vaccination. We also assessed the proportion of patients with deterioration of at least the minimal clinically important difference (MCID) between before first vaccination and 60 days thereafter. Results: We included 325 patients (median age = 59 years, interquartile range = 47-67, 156 [48%] female sex), of whom 137 (42%) had MG, 79 (24%) had CIDP, 43 (13%) had MMN, and 66 (20%) had IIM. PROM scores related to vaccination did not differ from scores unrelated to vaccination. In paired PROMs, MCID for deterioration was observed in three of 49 (6%) MG patients, of whom none reported a treatment change. In CIDP, MCID for deterioration was observed in eight of 29 patients (28%), of whom two of eight (25%) reported a treatment change. Conclusions: SARS-CoV-2 vaccination had no effect on daily functioning in patients with autoimmune neuromuscular diseases, confirming its safety in these patients