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The blood metabolome of cognitive function and brain health in middle-aged adults - influences of genes, gut microbiome, and exposome.
medRxiv
December 2024
Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Increasing evidence suggests the involvement of metabolic alterations in neurological disorders, including Alzheimer's disease (AD), and highlights the significance of the peripheral metabolome, influenced by genetic factors and modifiable environmental exposures, for brain health. In this study, we examined 1,387 metabolites in plasma samples from 1,082 dementia-free middle-aged participants of the population-based Rotterdam Study. We assessed the relation of metabolites with general cognition (G-factor) and magnetic resonance imaging (MRI) markers using linear regression and estimated the variance of these metabolites explained by genes, gut microbiome, lifestyle factors, common clinical comorbidities, and medication using gradient boosting decision tree analysis.
View Article and Find Full Text PDFArtificial Intelligence-Derived Risk Prediction: A Novel Risk Calculator Using Office and Ambulatory Blood Pressure.
Hypertension
January 2025
Department of Internal Medicine III, Cardiology, Angiology, Intensive Care Medicine, Universitätsklinikum des Saarlandes, Saarland University, Homburg/Saar, Germany (M.B., L.L., F.M.).
Background: Quantification of total cardiovascular risk is essential for individualizing hypertension treatment. This study aimed to develop and validate a novel, machine-learning-derived model to predict cardiovascular mortality risk using office blood pressure (OBP) and ambulatory blood pressure (ABP).
Methods: The performance of the novel risk score was compared with existing risk scores, and the possibility of predicting ABP phenotypes utilizing clinical variables was assessed.
Lipid phosphorylation by a diacylglycerol kinase suppresses ABA biosynthesis to regulate plant stress responses.
Mol Plant
February 2024
Department of Biology, University of Missouri-St. Louis, St. Louis, MO 63121, USA; Donald Danforth Plant Science Center, St. Louis, MO 63132, USA. Electronic address:
Lipid phosphorylation by diacylglycerol kinase (DGK) that produces phosphatidic acid (PA) plays important roles in various biological processes, including stress responses, but the underlying mechanisms remain elusive. Here, we show that DGK5 and its lipid product PA suppress ABA biosynthesis by interacting with ABA-DEFICIENT 2 (ABA2), a key ABA biosynthesis enzyme, to negatively modulate plant response to abiotic stress tested in Arabidopsis thaliana. Loss of DGK5 function rendered plants less damaged, whereas overexpression (OE) of DGK5 enhanced plant damage to water and salt stress.
View Article and Find Full Text PDFPreclinical Evaluation of the ATR Inhibitor BAY 1895344 as a Radiosensitizer for Head and Neck Squamous Cell Carcinoma.
Int J Radiat Oncol Biol Phys
April 2024
Department of Radiation Oncology, Duke University, Durham, North Carolina; Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Head and Neck Surgery & Communication Sciences, Duke University, Durham, North Carolina. Electronic address:
Purpose: Despite aggressive multimodal treatment that typically includes definitive or adjuvant radiation therapy (RT), locoregional recurrence rates approach 50% for patients with locally advanced human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). Thus, more effective therapeutics are needed to improve patient outcomes. We evaluated the radiosensitizing effects of ataxia telangiectasia and RAD3-related (ATR) inhibitor (ATRi) BAY 1895344 in preclinical models of HNSCC.
View Article and Find Full Text PDFAtrx deletion impairs CGAS/STING signaling and increases sarcoma response to radiation and oncolytic herpesvirus.
J Clin Invest
July 2023
Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
ATRX is one of the most frequently altered genes in solid tumors, and mutation is especially frequent in soft tissue sarcomas. However, the role of ATRX in tumor development and response to cancer therapies remains poorly understood. Here, we developed a primary mouse model of soft tissue sarcoma and showed that Atrx-deleted tumors were more sensitive to radiation therapy and to oncolytic herpesvirus.
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