Biology subjects

Maurmann, R. M.

Publications and source records attributed to Maurmann, R. M..

3 recordsLinked to original sources

bioRxiv2025

Immunoregulatory effect of metformin in monocytes exposed to SARS-CoV-2 spike protein subunit 1

BackgroundSevere COVID-19 is characterized by a hyperinflammatory state associated with an exacerbated inflammatory activation of monocytes and macrophages in the respiratory tract. Metformin has been identified as a potent monocyte inflammatory suppressor, and it has been demonstrated to attenuate inflammation in COVID-19. The mechanisms underlying metformin anti-inflammatory effects are, however, unclear. We thus sought to investigate metformins main interactions and their respective isolated effects in modulating monocyte inflammatory response to SARS-CoV-2 stimulation. MethodsClassical human monocytes were isolated from healthy 18-40-year-old individuals and stimulated in vitro with recombinant spike protein subunit 1 (rS1) to assess glycolytic and oxidative metabolic responses by Seahorse extracellular flux analysis, and inflammatory gene expression by qPCR. Stimulated monocytes were either pre-treated with metformin, rotenone, S1QEL, or A769662. ResultsMonocytes stimulated in vitro with rS1 showed an increased glycolytic response associated with production of pro-inflammatory cytokines. Metformin pre-treatment reduced glycolytic activation while partially suppressing inflammation. Rotenone-dependent mitochondrial complex I inhibition was not able to replicate the same effect, and neither complex I specific ROS scavenging. Conversely, A769662 induced AMPK activation led to suppressed glycolytic inflammatory response and cytokine expression pattern similar to metformin, thus suggesting AMPK modulation as a possible central component for metformins mode of action upon S1 stimulation. ConclusionsIn summary, further investigation into the interactions underlying AMPK activity on monocytes in the context of SARS-CoV-2 may provide a better elucidation of metformins anti-inflammatory effect.

immunology↗

bioRxiv2024

Modulatory Effects of Mdivi-1 on OxLDL-Induced Metabolic Alterations, Inflammatory Responses, and Foam Cell Formation in Human Monocytes

Atherosclerosis, a major contributor to cardiovascular disease, involves lipid accumulation and inflammatory processes in arterial walls, with oxidized low-density lipoprotein (OxLDL) playing a central role. OxLDL is increased during aging and stimulates monocyte transformation into foam cells and induces metabolic reprogramming and pro-inflammatory responses, accelerating atherosclerosis progression and contributing to other age-related diseases. This study investigated the effects of Mdivi-1, a mitochondrial fission inhibitor, and S1QEL, a selective complex I-associated reactive oxygen species (ROS) inhibitor, on OxLDL-induced responses in monocytes. Healthy monocytes isolated from participants were treated with OxLDL, with or without Mdivi-1 or S1QEL, and assessed for metabolic shifts, inflammatory cytokine expression, foam cell formation, and ROS production. OxLDL treatment elevated glycolytic activity (ECAR) and expression of pro-inflammatory cytokines IL1B and CXCL8, promoting foam cell formation and mitochondrial ROS (mtROS) production. Mdivi-1 and S1QEL effectively reduced OxLDL-induced glycolytic reprogramming, inflammatory cytokine levels, and foam cell formation while limiting mtROS. These findings suggest that both Mdivi-1 and S1QEL modulate key monocyte responses to OxLDL, providing insights into potential therapeutic approaches for age-related diseases.

immunology↗

bioRxiv2023

PseudoCell: A collaborative network for in silico prediction of regulatory pathways

Premature cellular senescence is a pivotal process in aging and age-related diseases, triggered by various stressors. However, this is not a homogeneous phenotype, but a heterogeneous cellular state composed of multiple senescence programs with different compositions. Therefore, understanding the complex dynamics of senescence programs requires a systemic approach. We introduce PseudoCell, a multi-valued logical regulatory network designed to explore the molecular intricacies of premature senescence. PseudoCell integrates key senescence signaling pathways and molecular mechanisms, offering a versatile platform for investigating diverse premature senescence programs initiated by different stimuli. Validation through simulation of classical senescence programs, including oxidative stress-induced senescence (OSIS) and oncogene-induced senescence (OIS), demonstrates its ability to replicate molecular signatures consistent with empirical data. Additionally, we explore the role of CCL11, a novel senescence-associated molecule, through simulations that reveal potential pathways and mechanisms underlying CCL11-mediated senescence induction. In conclusion, PseudoCell provides a systematic approach to dissecting premature senescence programs and uncovering novel regulatory mechanisms.

bioinformatics↗