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Sepsis is a life-threatening condition arising from immune dysregulation, particularly in patients with underlying diseases like rheumatoid arthritis (RA). However, experimental data on this phenomenon are lacking. Using flow cytometry, we investigated immune responses in mice with or without collagen-induced arthritis (CIA) following Streptococcus infection. Mice without CIA effectively cleared the infection, maintained hematopoiesis, and mobilized lymphocytes. In contrast, CIA mice exhibited impaired bacterial clearance, leukopenia, and sepsis. Emergency hematopoiesis in CIA mice led to depletion of lineage-committed progenitor cells, correlating with an accumulation of immature neutrophils that exhibited diminished cytokinogenesis. Notably, immune dysregulation in CIA mice appeared before sepsis onset. We detected an increase in neutrophils and monocytes in draining lymph nodes and joints. Importantly, lymphadenopathy and hyperactivated synovial fibroblasts, along with articular immune cell infiltration, drove excessive cytokine production, increasing sepsis risk. Our findings emphasize the importance of rigorous medical management of RA to mitigate infection-related complications. Graphical Abstract Diagram illustrating the relationship between blood infection and sepsis risk, with a gradient from resilience to sepsis risk. On the left, under “Healthy,” qualities include mature leukocyte persistence and stable hematopoiesis. On the right, under “Arthritis,” conditions include leukopenia and cytokine hyperproduction. A mouse represents blood infection at the top.

Cartilage-derived migratory cells show great potential for autologous use in cartilage repair surgery. However, their collection through arthroscopic biopsy has not been previously reported in individuals without osteoarthritis. This study aimed to characterize migratory cartilage cells isolated from arthroscopic biopsies of volunteers without osteoarthritis and compare them with cells obtained by enzymatic digestion. Cell cultures were successfully established using both methods—enzymatic digestion and cell migration—from cartilage explants, with no significant differences observed in stem cell markers or plasticity between the cell lines. Cells derived from both procedures exhibited characteristics of mesenchymal stem cell, including fibroblast-like morphology, expression of CD29, CD90, and CD105 markers, absence of hematopoietic and endothelial cell markers, and the ability to differentiate into adipocytes, chondrocytes, and osteoblasts under appropriate conditions. Cells obtained by migration showed lower expression of collagen I and II, along with reduce collagen II/collagen I ratio, both positively associated with chondral matrix production, as well as lower RUNX2 expression. However, no differences were found in the levels of SOX9, essential for chondrogenic differentiation, or in the expression of perlecan gene. Syndecan-1 expression was lower in cells obtained by migration. In conclusion, this study demonstrates that cartilage-derived migratory cells can be successfully obtained from arthroscopic biopsies of individuals without osteoarthritis, presenting comparable dedifferentiation and plasticity profiles. Furthermore, these cells express essential chondrogenic markers and proteins. Although further in vivo studies are needed to determine their effective regenerative potential, cartilage-derived migratory cells represent a promising avenue for cartilage repair strategies.

Haloperidol is a typical antipsychotic used to treat schizophrenia and induces dopamine D2 receptor antagonism. Long-term use of haloperidol can reduce brain size in animals and humans; however, the underlying mechanism of this effect remains unclear. Notch1 signaling regulates the development and function of the nervous system by balancing stem cell proliferation and differentiation. Therefore, we investigated the effects of long-term exposure to haloperidol on human-derived brain organoids, which served as sophisticated in vitro models of human brain development. Long-term exposure to haloperidol reduced the size of brain organoids and decreased the ventricular zone and Notch1 signaling. When propionate, which protects against haloperidol-induced toxicity, was combined with haloperidol, it rescued both the overall size of brain organoids and Notch1 expression levels. Additionally, treatment with valproic acid, a Notch1 activator, partially restored the size of brain organoids and the thickness of the ventricular layer. Taken together, these data suggest that long-term exposure to haloperidol impairs neurodevelopment via Notch1 signaling in brain organoids. These findings contribute to our understanding of antipsychotic drug safety and provide information for new neurodevelopmental toxicity assessments.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-08855-w.