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| http://dx.doi.org/10.1016/j.jcmgh.2020.03.005 | DOI Listing |
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Mitochondria complex III-generated superoxide is essential for IL-10 secretion in macrophages.
Sci Adv
January 2025
Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Mitochondrial electron transport chain (ETC) function modulates macrophage biology; however, mechanisms underlying mitochondria ETC control of macrophage immune responses are not fully understood. Here, we report that mutant mice with mitochondria ETC complex III (CIII)-deficient macrophages exhibit increased susceptibility to influenza A virus (IAV) and LPS-induced endotoxic shock. Cultured bone marrow-derived macrophages (BMDMs) isolated from these mitochondria CIII-deficient mice released less IL-10 than controls following TLR3 or TLR4 stimulation.
View Article and Find Full Text PDFMuscular TOR knockdown and endurance exercise ameliorate high salt and age-related skeletal muscle degradation by activating the MTOR-mediated pathway.
PLoS One
January 2025
Physical Culture Institute Ludong University, City Yantai, Shandong Province, China.
The target of rapamycin(TOR)gene is closely related to metabolism and cellular aging, but it is unclear whether the TOR pathways mediate endurance exercise against the accelerated aging of skeletal muscle induced by high salt intake. In this study, muscular TOR gene overexpression and RNAi were constructed by constructing MhcGAL4/TOR-overexpression and MhcGAL4/TORUAS-RNAi systems in Drosophila. The results showed that muscle TOR knockdown and endurance exercise significantly increased the climbing speed, climbing endurance, the expression of autophagy related gene 2(ATG2), silent information regulator 2(SIR2), and pparγ coactivator 1(PGC-1α) genes, and superoxide dismutases(SOD) activity, but it decreased the expression of the TOR gene and reactive oxygen species(ROS) level, and it protected the myofibrillar fibers and mitochondria of skeletal muscle in Drosophila on a high-salt diet.
View Article and Find Full Text PDFInsights into the role of phosphorylation on microtubule crosslinking by PRC1.
Mol Biol Cell
January 2025
Department of Biological Sciences, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
The mitotic spindle is composed of distinct networks of microtubules, including interpolar bundles that can bridge sister kinetochore fibers and bundles that organize the spindle midzone in anaphase. The crosslinking protein PRC1 can mediate such bundling interactions between antiparallel microtubules. PRC1 is a substrate of mitotic kinases including CDK/cyclin-B, suggesting that it can be phosphorylated in metaphase and dephosphorylated in anaphase.
View Article and Find Full Text PDFOptimizing kinase and PARP inhibitor combinations through machine learning and in silico approaches for targeted brain cancer therapy.
Mol Divers
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Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
The drug combination is an attractive approach for cancer treatment. PARP and kinase inhibitors have recently been explored against cancer cells, but their combination has not been investigated comprehensively. In this study, we used various drug combination databases to build ML models for drug combinations against brain cancer cells.
View Article and Find Full Text PDFPhase I trial of ATR inhibitor elimusertib with FOLFIRI in advanced or metastatic gastrointestinal malignancies (ETCTN 10406).
Cancer Chemother Pharmacol
January 2025
Cancer Therapeutics Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Background: ATR is an apical DDR kinase activated at damaged replication forks. Elimusertib is an oral ATR inhibitor and potentiates irinotecan in human colorectal cancer models.
Methods: To establish dose and tolerability of elimusertib with FOLFIRI, a Bayesian Optimal Interval trial design was pursued.
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