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Advances in modeling permeability and selectivity of the blood-brain barrier using microfluidics.
Microfluid Nanofluidics
July 2024
Department of Biomedical Engineering, The University of Arizona, 1200 E University Blvd, Tucson 85721, Arizona, USA.
The blood-brain barrier (BBB) protects the brain by actively allowing the entry of ions and nutrients while limiting the passage of from toxins and pathogens. A healthy BBB has low permeability and high selectivity to maintain normal brain functions. Increased BBB permeability can result from neurological diseases and traumatic injuries.
View Article and Find Full Text PDFFertigation with alpha-tocopherol enhances morphological, physiological, and antioxidant responses in radish (Raphanus sativus L.) under drought stress.
BMC Plant Biol
January 2025
Plant Production Department, College of Food and Agricultural Sciences, King Saud University, P.O. Box. 2460, Riyadh, 11451, Saudi Arabia.
Water scarcity is a foremost environmental concern and is expected to hasten in the forthcoming years due to severe fluctuations in weather patterns worldwide. The present work was designed to explore the potential role of alpha-tocopherol (α-Toc), a form of vitamin E, on the morphological, physio-biochemical, and cellular antioxidant responses of two radish genotypes grown under drought conditions (38 ± 3% of field capacity). The individual and combined applications of α-Toc (100 ppm) were used as T0- Control, T1- Control + TF (TF-alpha-tocopherol), T2- Drought (D), and T3- D + TF with three replications.
View Article and Find Full Text PDFComplex rearrangements fuel ER and HER2 breast tumours.
Nature
January 2025
Stanford Cancer Institute, School of Medicine, Stanford University, Stanford, CA, USA.
Breast cancer is a highly heterogeneous disease whose prognosis and treatment as defined by the expression of three receptors-oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 (HER2; encoded by ERBB2)-is insufficient to capture the full spectrum of clinical outcomes and therapeutic vulnerabilities. Previously, we demonstrated that transcriptional and genomic profiles define eleven integrative subtypes with distinct clinical outcomes, including four ER subtypes with increased risk of relapse decades after diagnosis. Here, to determine whether these subtypes reflect distinct evolutionary histories, interactions with the immune system and pathway dependencies, we established a meta-cohort of 1,828 breast tumours spanning pre-invasive, primary invasive and metastatic disease with whole-genome and transcriptome sequencing.
View Article and Find Full Text PDFKLF5 loss sensitizes cells to ATR inhibition and is synthetic lethal with ARID1A deficiency.
Nat Commun
January 2025
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
ATR plays key roles in cellular responses to DNA damage and replication stress, a pervasive feature of cancer cells. ATR inhibitors (ATRi) are in clinical development for treating various cancers, including those with high replication stress, such as is elicited by ARID1A deficiency, but the cellular mechanisms that determine ATRi efficacy in such backgrounds are unclear. Here, we have conducted unbiased genome-scale CRISPR screens in ARID1A-deficient and proficient cells treated with ATRi.
View Article and Find Full Text PDFThe protective effects of liraglutide in reducing lipid droplets accumulation and myocardial fibrosis in diabetic cardiomyopathy.
Cell Mol Life Sci
January 2025
Institute of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd, Taichung City, 402, Taiwan.
Background: Diabetes is a primary contributor to diabetic cardiomyopathy (DbCM), which is marked by metabolic imbalances such as elevated blood glucose and lipid levels, leading to significant structural and functional alterations in the myocardium. Elevated free fatty acids (FFAs) and hyperglycemia play critical roles in DbCM development, with FFAs inducing insulin resistance in cardiomyocytes and promoting lipid accumulation, resulting in oxidative stress and fibrosis. Current research suggests that glucagon-like peptide-1 (GLP-1) receptor agonists may effectively mitigate DbCM, although an effective treatment for this condition remains elusive, and the precise mechanisms of this protective effect are not fully understood.
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