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PKCδ germline variants and genetic deletion in mice augment antitumor immunity through regulation of myeloid cells.
Cancer Immunol Res
January 2025
University of Chicago, Chicago, IL, United States.
Based on the notion that hypomorphic germline genetic variants are linked to autoimmune diseases, we reasoned that novel targets for cancer immunotherapy might be identified through germline variants associated with greater T-cell infiltration into tumors. Here, we report that while investigating germline polymorphisms associated with a tumor immune gene signature, we identified PKCδ as a candidate. Genetic deletion of PKCδ in mice resulted in improved endogenous antitumor immunity and increased efficacy of anti-PD-L1.
View Article and Find Full Text PDFGenistein-3'-sodium sulfonate suppresses NLRP3-mediated cell pyroptosis after cerebral ischemia.
Metab Brain Dis
January 2025
Key Laboratory of Prevention and treatment of cardiovascular and cerebrovascular diseases of Ministry of Education, Gannan Medical University, Ganzhou, 341000, China.
Cerebral ischemia-induced pyroptosis contributes to the dissemination of neuroinflammation, and Nod-like receptor protein-3 (NLRP3) inflammasome plays a key role in this process. Previous studies have indicated that Genistein-3'-sodiumsulfonate (GSS) can inhibit neuroinflammation caused by cerebral ischemia, exert cerebroprotective effects, but its specific mechanism has not been comprehensively understood. The aim of this study was to explore the effect of GSS on ischemic stroke-induced cell pyroptosis.
View Article and Find Full Text PDFTeMac™ ameliorates memory impairment and cholinergic dysfunction in rats induced by scopolamine.
Metab Brain Dis
January 2025
Department of Biochemistry, Faculty of Science, University of Yaoundé 1, P.O. Box 812, Yaounde, Cameroon.
Alzheimer's disease (AD) is associated with cognitive impairments which are linked to a deficit in cholinergic function. The objective of this study was to evaluate the ability of TeMac™ to prevent memory impairment in scopolamine-rats model of Alzheimer's disease and by in silico approaches to identify molecules in TeMac™ inhibiting acetylcholinesterase. The cholinergic cognitive dysfunction was induced by intraperitoneal injection of scopolamine (1 mg/kg daily) in male Wistar rats for seven consecutive days.
View Article and Find Full Text PDFThe CD74 inhibitor DRhQ improves short-term memory and mitochondrial function in 5xFAD mouse model of Aβ accumulation.
Metab Brain Dis
January 2025
Department of Neurology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Neuroinflammation and mitochondrial dysfunction are early events in Alzheimer's disease (AD) and contribute to neurodegeneration and cognitive impairment. Evidence suggests that the inflammatory axis mediated by macrophage migration inhibitory factor (MIF) binding to its receptor, CD74, plays an important role in many central nervous system (CNS) disorders such as AD. Our group has developed DRhQ, a novel CD74 binding construct which competitively inhibits MIF binding, blocks macrophage activation and migration into the CNS, enhances anti-inflammatory microglia cell numbers and reduces pro-inflammatory gene expression.
View Article and Find Full Text PDFNarciclasine attenuates sepsis-associated acute kidney injury through the ESR1/S100A11 axis.
Funct Integr Genomics
January 2025
Department of Emergency and Critical Care Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, People's Republic of China.
Narciclasine (Ncs) was effective in sepsis management due to its antioxidant properties. The present study dissected the protective effects of Ncs against sepsis-associated acute kidney injury (SA-AKI) and the molecular mechanisms. The SA-AKI mice were developed using cecum ligation and puncture and pretreated with Ncs and adenoviruses.
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