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Signaling molecules in cellular responses to foreign stimuli are described as static up- or down-concentration changes during signal transduction. This is because analytical methods for transducing molecules are much slower than the signaling events. In this study, we develop a dynamic cell model and reveal the temporal regulation of signal transduction events in response to reactive oxygen species (ROS). The model contained a set of 10 batches of redox-modified cells that mimic the temporal ROS accumulation events. Validating this dynamic cell model, we discover that cells survive early ROS attacks by activating the Nrf2/polysulfide/p62/CDK1 pathway. Nearly all signaling molecules exhibit time-dependent V-shape or inverse V-shape activation/feedback regulation dynamics in response to ROS accumulation. The results show that the dynamic cell model approach is invaluable for revealing complex signal intensity- and time-dependent cell signaling events.
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http://dx.doi.org/10.1093/pnasnexus/pgae020 | DOI Listing |
Proc Natl Acad Sci U S A
September 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug De
Proliferative retinopathy is a leading cause of irreversible blindness in humans; however, the molecular mechanisms behind the immune cell-mediated retinal angiogenesis remain poorly elucidated. Here, using single-cell RNA sequencing in an oxygen-induced retinopathy (OIR) model, we identified an enrichment of sorting nexin (SNX)-related pathways, with SNX3, a member of the SNX family that is involved in endosomal sorting and trafficking, being significantly upregulated in the myeloid cell subpopulations of OIR retinas. Immunostaining showed that SNX3 expression is markedly increased in the retinal microglia/macrophages of mice with OIR, which is mainly located within and around the neovascular tufts.
View Article and Find Full Text PDFIn Vitro Cell Dev Biol Anim
September 2025
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan.
S100 protein family members S100A8 and S100A9 function primarily as a heterodimer complex (S100A8/A9) in vivo. This complex has been implicated in various cancers, including gastric cancer (GC). Recent studies suggest that these proteins play significant roles in tumor progression, inflammation, and metastasis.
View Article and Find Full Text PDFCurr Genet
September 2025
Fermentation and Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi, 180001, India.
Trichoderma species exhibit remarkable versatility in adaptability and in occupying habitats with lifestyles ranging from mycoparasitism and saprotrophy to endophytism. In this study, we present the first high-quality whole-genome assembly and annotation of T. lixii using Illumina HiSeq technology to explore the mechanisms of endophytic lifestyle and plant colonization.
View Article and Find Full Text PDFMol Biol Rep
September 2025
Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
Neuroinflammation, a vital protective response for tissue homeostasis, becomes a detrimental force when chronic and dysregulated, driving neurological disorders like Alzheimer's, Parkinson's, and Huntington's diseases. Potassium (K) channels maintain membrane potential and cellular excitability in neurons and glia within the intricate CNS signaling network. Neuronal injury or inflammation can disrupt K channel activity, leading to hyperexcitability and chronic pain.
View Article and Find Full Text PDFACS Sens
September 2025
School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Alpha-2-macroglobulin (A2M) is a critical biomarker implicated in inflammation, immune regulation, coagulation, and various pathological conditions such as liver fibrosis, neurodegenerative diseases, and cancers. However, its precise quantification remains challenging due to complex conformational dynamics, subtle abundance fluctuations, and interference from plasma proteins. Here, we present a label-free dynamic single-molecule sensing (LFDSMS) strategy for the sensitive and specific detection of A2M.
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