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Background: Many RRMS patients who had been treated for over 20 years with GA 20 mg/ml daily (GA20) switched to 40 mg/ml three times-a-week (GA40) to reduce injection-related adverse events. Although GA40 is as effective as GA20 in reducing annualized relapse rate and MRI activity, it remains unknown how switching to GA40 from GA20 affects the development of pathogenic and regulatory immune cells. Objective: To investigate the difference in immunological parameters in response to GA20 and GA40 treatments. Methods: We analyzed five pro-inflammatory cytokines (IL-1b, IL-23, IL-12, IL-18, TNF-a), and three anti-inflammatory/regulatory cytokines (IL-10, IL-13, and IL-27) in serum. In addition, we analyzed six cytokines (IFN-c, IL-17A, GM-CSF, IL-10, IL-6, and IL-27) in cultured PBMC supernatants. The development of Th1, Th17, Foxp3 Tregs, M1-like, and M2-like macrophages were examined by flow cytometry. Samples were analyzed before and 12 months post switching to GA40 or GA20. Results: Pro- and anti-inflammatory cytokines were comparable between the GA40 and GA20 groups. Development of Th1, Th17, M1-like macrophages, M2-like macrophages, and Foxp3 Tregs was also comparable between the two groups. Conclusions: The immunological parameters measured in RRMS patients treated with GA40 three times weekly are largely comparable to those given daily GA20 treatment. [ABSTRACT FROM AUTHOR]

Management of the gastro-toxicity of non-steroidal anti-inflammatory drugs (NSAIDs) remains a crucial problem, because the commercially available anti-ulcer drugs have side effects and are often expensive. Hence, the potential of a new water-soluble GPx mimic, DL- trans-3,4-dihydroxy-1-selenolane (DHSred) in healing the indomethacin-induced stomach ulceration in mice was examined. Administration of indomethacin (18 mg/kg, p. o.) induced ulceration in the glandular portion of the gastric mucosa, accompanied by increased lipid peroxidation (1.3-fold, p <0.001) and protein oxidation (1.5-fold, p < 0.001), depletion of thiol-defense (42.5%, p < 0.01), plasma total antioxidant status (53.4%, p < 0.001) and mucin (47.5%, p < 0.01), as well as reduced expressions of cyclooxygenases and prostaglandin synthesis (54.7%, p < 0.001) in the gastric tissues of mice. Daily oral administration of DHSred (2.5 mg/kg) or omeprazole (Omez) (3 mg/kg) for 3 days respectively produced ˜74% and 69% ( p < 0.001) healing of the acute gastric ulceration. The test samples also significantly reversed all the adverse effects of indomethacin on the biochemical parameters. Apparently, the gastric ulcer healing action of DHSred and Omez was due to their antioxidant action and their ability to protect mucin and augment PG synthesis by upregulation of the COX isozymes. The results suggested that the non-toxic and inexpensive compound, DHSred, may be a good candidate for further evaluation as a potent anti-ulcer drug. [ABSTRACT FROM AUTHOR]

The modulation of the cyclooxygenase-independent pathway by black tea (BT) and its constituent theaflavins (TFs) during their healing action against indomethacin-induced stomach ulceration in mice was investigated. On the 3rd day of its administration, indomethacin (18 mg/kg) induced maximum stomach ulceration, which was associated with increased myeloperoxidase (MPO) activity (93.3%, p < 0.001), and inducible nitric oxide synthase (iNOS) expression (1.6-fold, p < 0.001), along with augmented levels of serum nitrite (1.5-fold, p < 0.001), selectins and cell adhesion molecules (CAMs), as well as reduced endothelial nitric oxide synthase (eNOS) expression (60%, p < 0.001). Treatment with BT (40 mg/kg) and TF (1 mg/kg) for 3 days reversed these parameters and provided excellent (78--81%) ulcer healing. However, alterations of NOS expressions and levels of selectins and CAMs were only partially responsible for the excellent healing capacity (∼∼80%) of omeprazole (3 mg/kg ×× 3 days). [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Recent studies suggest that migration of Th1 and Th17 cells specific for enteric bacteria from the gut to the CNS may lead to the initiation and/or exacerbation of autoimmune diseases including MS. Human leukocyte antigen (HLA)-DR15 is an MHC class II (MHCII) haplotype highly associated with the development of MS that contains the two HLA-DRB* genes, DRB1*1501 (DR2b) and DRB5*0101 (DR2a). To identify enteric bacteria which harbor antigenic epitopes that activate myelin-specific T cells and drive CNS inflammation, we screened for enteric bacteria which express cross-reactive epitopes ('mimotopes') of an immunodominant myelin basic protein 89–98 (MBP89-98) epitope. Based on known MHCII HLA-DR2a amino acid binding motifs and cultivation with splenic T cells isolated from MBP-T cell receptor (TCR)/DR2a transgenic (Tg) mice, we discovered that a certain variant of surface layer protein A (SLPA), which is expressed by a subtype of Clostridioides difficile, contains an amino acid sequence that activates MBP89-98-reactive T cells. Furthermore, activation of MBP-specific T cells by SLPA upon active immunization induced experimental autoimmune encephalomyelitis (EAE) in MBP-TCR/DR2a Tg mice. This study suggests that a unique strain of C. difficile possesses an encephalitogenic mimotope of MBP that activates autoreactive, myelin-specific T cells. [ABSTRACT FROM AUTHOR]

The study assessed the diagnostic value of diffusion-weighted imaging (DWI) and mean apparent diffusion coefficient (ADC) in early acute interstitial edematous pancreatitis (AIEP). Fifty-six AIEP patients and 60 healthy controls underwent an upper abdominal magnetic resonance (MR) examination. The pancreas diameter and ADC values were measured and analyzed across age and gender groups. Results showed that the pancreas diameter varied with sex and age, with smaller diameters in females and the elderly. Mean ADC values were not significantly affected by age or sex. Signal changes were observed in AIEP patients' images, with DWI showing a higher positive rate than T1WI and T2WI. Comparing the control and AIEP groups, the pancreas diameter was significantly larger in AIEP patients, particularly the pancreatic tail in males. ADC values were significantly lower in AIEP patients, and the difference was more pronounced at b=800 s/mm² compared to b=500 s/mm². Mean ADC exhibited good diagnostic potential for early AIEP, with higher sensitivity and specificity values than serum amylase levels. The area under the receiver operating characteristic (ROC) curve (AUC) indicated that the diagnostic value was better at b=800 s/mm² than at b=500 s/mm². In conclusion, the study found that normal pancreas diameter is influenced by sex and age, with smaller diameters in females and the elderly. Mean ADC values were not affected by these factors. Early AIEP could not be diagnosed solely based on pancreas diameter changes. DWI combined with Mean ADC demonstrated high diagnostic value for early AIEP., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Dali University issued approval #202101BA070001-130. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This work is supported by the Science and Technology Planning Project of Yunnan Provincial Science and Technology Department. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yadav et al.)