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Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease affecting primarily the upper and lower motor neurons. A common feature of all ALS cases is a well-characterized neuroinflammatory reaction within the central nervous system (CNS). However, much less is known about the role of the peripheral immune system and its interplay with CNS resident immune cells in motor neuron degeneration. Here, we characterized peripheral monocytes in both temporal and spatial dimensions of ALS pathogenesis. We found the circulating monocytes to be deregulated in ALS regarding subtype constitution, function and gene expression. Moreover, we show that CNS infiltration of peripheral monocytes correlates with improved motor neuron survival in a genetic ALS mouse model. Furthermore, application of human immunoglobulins or fusion proteins containing only the human Fc, but not the Fab antibody fragment, increased CNS invasion of peripheral monocytes and delayed the disease onset. Our results underline the importance of peripheral monocytes in ALS pathogenesis and are in agreement with a protective role of monocytes in the early phase of the disease. The possibility to boost this beneficial function of peripheral monocytes by application of human immunoglobulins should be evaluated in clinical trials.

Adhesion of monocytes to micro-injuries on arterial walls is an important early step in the occurrence and development of degenerative atherosclerotic lesions. At these injuries, collagen is exposed to the blood stream. We are interested whether age influences monocyte adhesion to collagen under flow, and hence influences the susceptibility to arteriosclerotic lesions. Therefore, we studied adhesion and rolling of human peripheral blood monocytes from old and young individuals on collagen type I coated surface under shear flow. We find that firm adhesion of monocytes to collagen type I is elevated in old individuals. Pre-stimulation by lipopolysaccharide increases the firm adhesion of monocytes homogeneously in older individuals, but heterogeneously in young individuals. Blocking integrin α x showed that adhesion of monocytes to collagen type I is specific to the main collagen binding integrin α x β 2 . Surprisingly, we find no significant age-dependent difference in gene expression of integrin α x or integrin β 2 . However, if all integrins are activated from the outside, no differences exist between the age groups. Altered integrin activation therefore causes the increased adhesion. Our results show that the basal increase in integrin activation in monocytes from old individuals increases monocyte adhesion to collagen and therefore the risk for arteriosclerotic plaques.

Cellular differentiation involves complex events associated with changes in cellular shape, function and proliferative capacity. This process is regulated by specific expression of multiple genes, which guide the cell through differentiation but also ensure proper function of terminal cell types. Over the last decade, the role of cellular metabolism in maintaining stem cells pluripotency and differentiation has been getting more attention due to a direct link between metabolic state and differentiation potential of cells. Since Nuclear Myosin 1 (NM1) deletion leads to a switch from oxidative phosphorylation to aerobic glycolysis and tumorigenesis in mice, here we asked if NM1 also contributes to cell differentiation. Indeed, analysis of metabolomic profiles and cytokine and chemokine levels upon NM1 depletion support a role in hematopoiesis. In an NM1 KO mouse model results from total blood cell count and bleeding assay show decreased erythropoiesis and thrombopoiesis as well as failure in hemostasis. Next, we explored the role of NM1 during the differentiation of hematopoietic progenitor stem cells to terminal blood cells by transcriptionally profiling bone marrow, spleen and peripheral blood from NM1 KO mice. We found that in bone marrow, NM1 deletion leads to overexpression of genes associated with glycolysis-dependent platelet activation and suppression of the innate immune system. These expression patterns are preserved and become more complex in spleen and peripheral blood. The study, therefore, provides insights into the underlying mechanisms of hematopoietic differentiation and activation of specific blood cell types and suggests NM1 as a potential therapeutic target for blood-related disorders.

Circular RNAs (circRNAs) are critical regulators in breast cancer (BC) progression, particularly through their interactions with the Wnt/β-catenin signaling pathway. This comprehensive review elucidates the regulatory roles of key circRNAs, including circABCC4, circFAT1, circARL8B, and circDONSON, in modulating BC behavior. These circRNAs primarily function as microRNA sponges, influencing essential processes such as proliferation, metastasis, drug resistance, and cell survival. For instance, circDONSON promotes tumor growth and radioresistance through SOX4-mediated Wnt signaling, whereas circRNF10 exhibits tumor-suppressive properties. The dual role of circRNAs as oncogenes or tumor suppressors highlights their complexity. Their high stability and tissue-specific expression patterns position them as promising diagnostic biomarkers and therapeutic targets. Dysregulation of circRNAs modulates Wnt/β-catenin signaling, a key driver of BC progression, promoting oncogenesis and therapeutic resistance. This review synthesizes evidence from peer-reviewed literature, emphasizing the molecular mechanisms and clinical implications of circRNA–Wnt interactions. By exploring these intricate networks, we identify novel opportunities for targeted BC therapies, underscoring the potential of circRNAs to transform diagnosis and treatment. Future research should prioritize standardizing circRNA quantification and validating findings across diverse patient cohorts to enhance clinical applicability. Graphical Abstract

The emerging COVID-19 pandemic led to a dramatic increase in global mortality and morbidity rates. As in most infections, fatal complications of coronavirus affliction are triggered by an untrammeled host inflammatory response. Cytokine storms created by high levels of interleukin and other cytokines elucidate the pathology of severe COVID-19. In this respect, repurposing drugs that are already available and might exhibit anti-inflammatory effects have received significant attention. With the in vitro and clinical investigation of several studies on the effect of antidepressants on COVID-19 prognosis, previous data suggest that selective serotonin reuptake inhibitors (SSRIs) might be the new hope for the early treatment of severely afflicted patients. SSRIs’ low cost and availability make them potentially eligible for COVID-19 repurposing. This review summarizes current achievements and literature about the connection between SSRIs administration and COVID-19 prognosis.