Search Results (2)

Multiple sclerosis (MS) is an immune-mediated, chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS). Immune cell infiltration can lead to permanent activation of macrophages and microglia in the parenchyma, resulting in demyelination and neurodegeneration. Thus, neurodegeneration that begins with acute lymphocytic inflammation may progress to chronic inflammation. This chronic inflammation is thought to underlie the development of so-called smouldering lesions. These lesions evolve from acute inflammatory lesions and are associated with continuous low-grade demyelination and neurodegeneration over many years. Their presence is associated with poor disease prognosis and promotes the transition to progressive MS, which may later manifest clinically as progressive MS when neurodegeneration exceeds the upper limit of functional compensation. In smouldering lesions, in the presence of only moderate inflammatory activity, a toxic environment is clearly identifiable and contributes to the progressive degeneration of neurons, axons, and oligodendrocytes and, thus, to clinical disease progression. In addition to the cells of the immune system, the development of oxidative stress in MS lesions, mitochondrial damage, and hypoxia caused by the resulting energy deficit and iron accumulation are thought to play a role in this process. In addition to classical immune mediators, this chronic toxic environment contains high concentrations of oxidants and iron ions, as well as the excitatory neurotransmitter glutamate. In this review, we will discuss how these pathobiochemical markers and mechanisms, alone or in combination, lead to neuronal, axonal, and glial cell death and ultimately to the process of neuroinflammation and neurodegeneration, and then discuss the concepts and conclusions that emerge from these findings. Understanding the role of these pathobiochemical markers would be important to gain a better insight into the relationship between the clinical classification and the pathomechanism of MS. Full article

Multiple myeloma (MM) is a hematological malignancy characterised by proliferation of clonal plasma cells (PCs) within the bone marrow (BM). Myelomagenesis is a multi-step process which goes from an asymptomatic phase, defined as monoclonal gammopathy of undetermined significance (MGUS), to a smouldering myeloma (SMM) stage, to a final active MM disease, characterised by hypercalcemia, renal failure, bone lesions anemia, and higher risk of infections. Overall, microRNAs (miRNAs) have shown to significantly impact on MM tumorigenesis, as a result of miRNA-dependent modulation of genes involved in pathways known to be crucial for MM pathogenesis and disease progression. We aim to revise the literature related to the role of miRNAs as potential diagnostic and prognostic biomarkers, thus highlighting their key role as novel players within the field of MM and related premalignant conditions. Full article