Aging is closely related to the main aspects of multiple sclerosis (MS). The average age of the MS population is increasing and the number of elderly MS patients is expected to increase. In addition to neurons, N-methyl-D-aspartate receptors (NMDARs) are also expressed on non-neuronal cells, such as immune cells. The aim of this study was to investigate the role of NMDARs in experimental autoimmune encephalomyelitis (EAE) in young and aged rats. Memantine, a non-competitive NMDAR antagonist, was administered to young and aged Dark Agouti rats from day 7 after immunization. Antagonizing NMDARs had a more favourable effect on clinical disease, reactivation, and apoptosis of CD4⁺ T cells in the target organ of aged EAE rats. The expression of the fractalkine receptor CX3CR1 was increased in memantine-treated rats, but to a greater extent in aged rats. Additionally, memantine increased Nrf2 and Nrf2-regulated enzymes’ mRNA expression in brain tissue. The concentrations of superoxide anion radicals, malondialdehyde, and advanced oxidation protein products in brain tissue were consistent with previous results. Overall, our results suggest that NMDARs play a more important role in the pathogenesis of EAE in aged than in young rats.

Notwithstanding prevalence gaps in micronutrients supporting immune functions, the significance of their deficits/supplementation for the efficacy of vaccines is underinvestigated. Thus, the influence of supplementation combining vitamins C and D, zinc, selenium, manganese, and N-acetyl cysteine on immune correlates/surrogates of protection conferred by a quadrivalent influenza vaccine (QIV) in mice was investigated. The supplementation starting 5 days before the first of two QIV injections given 28 days apart increased the serum titres of total and neutralizing IgG against each of four influenza strains from QIV. Accordingly, the frequencies of germinal center B cells, follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells increased in secondary lymphoid organs (SLOs). Additionally, the supplementation improved already increased IgG response to the second QIV injection by augmenting not only neutralizing antibody production, but also IgG2a response, which is important for virus clearance, through favoring Th1 differentiation as indicated by Th1 (IFN-γ)/Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely partly reflected antioxidant action of the supplement as indicated by splenic redox status analyses. Thus, the study provides a solid scientific background for further research aimed at repurposing the use of this safe and inexpensive micronutrient combination to improve response to the influenza vaccine.

The anti-inflammatory/immunomodulatory effects of Teucrium montanum L. (TM), a plant distributed in the Mediterranean region, have been insufficiently examined. The effects of the TM ethanol extract were tested in a rat collagen-induced arthritis (CIA) model of rheumatoid arthritis. LC-MS was used for the phytochemical analysis of the TM extract. Dark Agouti rats were immunized with bovine type II collagen (CII) in incomplete Freund’s adjuvant for CIA, and treated with 100 or 200 mg/kg of TM extract daily via oral administration. Clinical and histopathological evaluations and a flow cytometric analysis of the phenotypic and functional characteristics of splenocytes and draining lymph node cells were performed. The cytokines in the paw tissue culture supernatants and anti-CII antibodies in serum were determined by ELISA. The TM extract, with the dominant components verbascoside and luteolin 7-O-rutinoside, reduced the arthritic score and ankle joint inflammation in CIA rats, promoted the antioxidant profile in serum, and lowered pro-inflammatory TNF-α, IL-6 and IL-1β production. It suppressed the activation status of CD11b+ cells by lowering CD86, MHCII and TLR-4 expression, and promoted the Th17/T regulatory cell (Tregs) balance towards Tregs. A lower frequency of B cells was accompanied by a lower level of anti-CII antibodies in treated rats. These findings imply the favorable effect of TM extract on the clinical presentation of CIA, suggesting its anti-inflammatory/immunomodulatory action and potential therapeutic effect.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The disease develops through the interaction of multiple interconnected pathophysiological mechanisms, including insulin resistance, dysregulated lipid metabolism, oxidative stress, mitochondrial and endoplasmic reticulum dysfunction, chronic inflammation, gut–liver axis disruption, and progressive fibrogenesis. Betaine, a naturally occurring methyl donor, has been investigated as a potential therapeutic agent because of its diverse metabolic and cytoprotective effects. This review summarizes current knowledge on the mechanisms by which betaine may influence MASLD development and progression. Preclinical studies indicate that betaine improves insulin sensitivity and hepatic lipid homeostasis, reduces oxidative and endoplasmic reticulum stress, preserves mitochondrial function, mitigates inflammatory signaling, and limits hepatic fibrosis. In addition, growing evidence suggests that betaine contributes to the maintenance of gut–liver axis homeostasis, further supporting its beneficial effects on liver function. Although these findings are consistent across preclinical models, clinical evidence remains limited, and the therapeutic efficacy of betaine in patients with MASLD has not yet been established. Further well-designed clinical trials are required to determine its clinical value, optimal therapeutic strategy, and potential role in the management of MASLD.

Background: The Global Action Plan for Influenza Vaccines, launched by the World Health Organization in 2006, aimed to expand global manufacturing capacity, ensure equitable access to influenza vaccines, and reduce global vaccine shortages. The Institute of Virology, Vaccines and Sera “Torlak” was recognized as a partner and participated in a technology transfer programme to improve national production capabilities. Preclinical studies conducted in 2013 and 2014 provided comprehensive toxicological evidence supporting the safety of the trivalent influenza vaccine manufacturing platform. Nearly a decade later, this validated platform enabled the independent development of a quadrivalent influenza vaccine. Subsequent preclinical studies conducted in accordance with European Medicines Agency guidelines demonstrated preserved immunogenicity despite the inclusion of an additional antigen. Methods: Preclinical evaluation included standard safety and immunogenicity assessments in animal models. Safety assessment included evaluation of systemic parameters (general health status, leukocyte profile, blood biochemistry, and histopathology) and local reactions. Immunogenicity of both trivalent and quadrivalent formulations was assessed using haemagglutination inhibition and microneutralization assays. Results: No significant systemic or local adverse effects were observed. Both trivalent and quadrivalent formulations induced robust immune responses, with immunogenicity comparable to that of corresponding commercial vaccines. Conclusions: These findings confirm the safety profile and demonstrate strong immunogenicity for both the trivalent and quadrivalent formulations, supporting the successful establishment of a national influenza vaccine platform, contributing to increased pandemic preparedness and sustainable influenza vaccine production.