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TLR-mediated activation of dendritic cells (DCs) is associated with a metabolic transition in which mitochondrial oxidative phosphorylation is inhibited by endogenously synthesized NO and the cells become committed to glucose and aerobic glycolysis for survival. We show that inhibition of mechanistic target of rapamycin (mTOR) extends the lifespan of TLR-activated DCs by inhibiting the induction of NO production, thereby allowing the cells to continue to use their mitochondria to generate ATP, and allowing them the flexibility to use fatty acids or glucose as nutrients to fuel core metabolism. These data provide novel mechanistic insights into how mTOR modulates DC metabolism and cellular longevity following TLR activation and provide an explanation for previous findings that mTOR inhibition enhances the efficacy of DCs in autologous vaccination.
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http://dx.doi.org/10.4049/jimmunol.1302498 | DOI Listing |
Eur J Med Res
September 2025
Department of Zoology, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt.
Nuclear receptors (NRs) are a superfamily of ligand-activated transcription factors that regulate gene expression in response to metabolic, hormonal, and environmental signals. These receptors play a critical role in metabolic homeostasis, inflammation, immune function, and disease pathogenesis, positioning them as key therapeutic targets. This review explores the mechanistic roles of NRs such as PPARs, FXR, LXR, and thyroid hormone receptors (THRs) in regulating lipid and glucose metabolism, energy expenditure, cardiovascular health, and neurodegeneration.
View Article and Find Full Text PDFSci China Life Sci
September 2025
State Key Laboratory of Plant Environmental Resilience, College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
Diurnal floret opening and closure (DFOC) is essential for rice reproductive development and hybrid breeding, yet transcriptional dynamics and underlying regulatory networks remain poorly characterized. Here, we conducted high-temporal-resolution transcriptomic analyses of lodicules to dissect DFOC regulatory networks in two japonica rice cultivars. Analysis of differentially expressed genes (DEGs) uncovered core genes shared by both cultivars, primarily associated with jasmonic acid (JA) signaling and cell wall remodeling.
View Article and Find Full Text PDFEMBO J
September 2025
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, 94720, USA.
A variety of stressors, including environmental insults, pathological conditions, and transition states, constantly challenge cells that, in turn, activate adaptive responses to maintain homeostasis. Mitochondria have pivotal roles in orchestrating these responses that influence not only cellular energy production but also broader physiological processes. Mitochondria contribute to stress adaptation through mechanisms including induction of the mitochondrial unfolded protein response (UPR) and the integrated stress response (ISR).
View Article and Find Full Text PDFNat Rev Cancer
September 2025
Department of Neurology, Division of Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Neurotoxicity is a common and potentially severe adverse effect from conventional and novel cancer therapy. The mechanisms that underlie clinical symptoms of central and peripheral nervous system injury remain incompletely understood. For conventional cytotoxic chemotherapy or radiotherapy, direct toxicities to brain structures and neurovascular damage may result in myelin degradation and impaired neurogenesis, which eventually translates into delayed neurodegeneration accompanied by cognitive symptoms.
View Article and Find Full Text PDFBr J Cancer
September 2025
Institute of Life Sciences, Bhubaneswar, Odisha, India.
Background: Docetaxel is the most common chemotherapy regimen for several neoplasms, including advanced OSCC (Oral Squamous Cell Carcinoma). Unfortunately, chemoresistance leads to relapse and adverse disease outcomes.
Methods: We performed CRISPR-based kinome screening to identify potential players of Docetaxel resistance.