RESUMO
Multiple sclerosis (MS) is a chronic inflammatory, demyelinating, and neurodegenerative connective tissue disease affecting the central nervous system (CNS). Recently, there has been a dramatic improvement in several vital concepts of immune pathophysiology underlying MS. Notably, one of the prerequisites to MS development is Epstein-Barr virus (EBV) infection. Greater attention has been drawn towards promising, innovative immunotherapies in the management and treatment of MS. Whilst there are numerous immunotherapies currently proposed for MS, the B cell depleting therapy that predominantly uses the anti-CD20 monoclonal antibodies (mAbs) such as rituximab, ocrelizumab, and ofatumumab have demonstrated promising clinical benefits by targeting the memory B cells, which are the primary reservoir of EBV latency. Although mAbs have proved beneficial in the treatment of MS, they pose the risk of potential adverse effects. The current systematic review was undertaken to explore the therapeutic role of anti-CD20 therapy and its downsides in the treatment of MS and EBV infection. Clinical trials and prospective and retrospective studies reporting anti-CD20 therapy were carefully reviewed. The initial sections discuss the clinical features of MS, the probable link between EBV and MS, and the role of B cells in MS pathogenesis. Here, we show the potential role of anti-CD20 therapy more of a boon than a bane as the therapy yields more promising results for MS treatment. Nevertheless, the adverse effects could be minimized following a planned therapeutic regimen for treating MS patients.
RESUMO
Exposure to long-term chronic unpredictable mild stress (CUMS) can cause redox imbalance and inflammation, which may affect the integrity of the gut barrier. The present study was conducted to investigate the effects of a probiotics bacterium mixture, including Clostridium butyricum (C. butyricum) and Bifidobacterium infantis (B. infantis), on the intestinal homeostasis in rats exposed to multiple low-intensity stressors for 28 days. The mechanism of CUMS-induced altered intestinal homeostasis was evaluated by focusing on the nuclear factor-E2-related factor-2 (Nrf-2) pathway. In contrast to the CUMS group, probiotic mixture supplementation significantly (p < 0.01) reversed the stress-induced elevated corticosterone level, protein and lipid oxidation, and increased enzymatic and non-enzymatic antioxidant levels, as well as upregulated Nrf-2/HO-1 pathway. Probiotics supplementation further significantly (p < 0.01) decreased the CUMS-induced inflammation, altered T-lymphocyte levels, and suppressed the protein expression of nuclear factor kappa B (NF-κB) in rat intestines. Improvement in histological changes and intestinal barrier integrity further validate the beneficial effects of probiotic mixtures on CUMS-induced altered intestinal morphology. In conclusion, our results suggest that the combination of C. butyricum and B. infantis significantly attenuated CUMS-induced oxidative stress, inflammation, and T-lymphocyte modulation by upregulating Nrf-2/HO-1 signaling and inhibiting NF-κB expression in rat intestine.
