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http://dx.doi.org/10.5045/br.2022.2022134 | DOI Listing |
Fluids Barriers CNS
January 2025
Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven - University of Leuven, O&N II Herestraat 49 box 820, 3000, Leuven, Belgium.
Background: Therapeutic antibodies for the treatment of neurological disease show great potential, but their applications are rather limited due to limited brain exposure. The most well-studied approach to enhance brain influx of protein therapeutics, is receptor-mediated transcytosis (RMT) by targeting nutrient receptors to shuttle protein therapeutics over the blood-brain barrier (BBB) along with their endogenous cargos. While higher brain exposure is achieved with RMT, the timeframe is short due to rather fast brain clearance.
View Article and Find Full Text PDFThe human () gene encodes a plasma membrane protein SLC39A8 (ZIP8) that mediates the specific uptake of the metals Cd, Mn, Zn, Fe, Co, and Se Pathogenic variants within are associated with congenital disorder of glycosylation type 2 (CDG type II) or Leigh-like syndrome. However, numerous mutations of uncertain significance are also linked to different conditions or benign traits. Our study characterized 21 variants and measured their impact on protein localization and intracellular levels of Cd, Zn, and Mn We identified four variants that disrupt protein expression, five variants with high retention in the endoplasmic reticulum, and 12 variants with localization to the plasma membrane.
View Article and Find Full Text PDFDrug Metab Dispos
January 2025
Centre for Applied Pharmacokinetic Research, University of Manchester, Manchester, United Kingdom; Certara Predictive Technologies, Sheffield, United Kingdom.
The placenta acts as a barrier, excluding noxious substances while actively transferring nutrients to the fetus, mediated by various transporters. This study quantified the expression of key placental transporters in term human placenta (n = 5) and BeWo, BeWo b30, and JEG-3 placenta cell lines. Combining these results with pregnancy physiologically based pharmacokinetic (PBPK) modeling, we demonstrate the utility of proteomic analysis for predicting placental drug disposition and fetal exposure.
View Article and Find Full Text PDFAnal Chem
January 2025
Guangdong Key Laboratory of Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, P. R. China.
Understanding the molecular energy metabolism of single cells in the nucleolus stress response induced by mild-photothermal therapy (mPTT) is of great importance for investigating the photothermal lethal mechanism. Herein, we successfully fabricated a "turn-on"-type fluorescent nanoprobe based on the fluorescently labeled aptamers (FAM-ATP-apt and Cy3-GTP-apt) and TiCT MXene. When the adapters on the nanoprobes bonded to intracellular ATP and GTP, the fluorescence of the nanoprobes was restored.
View Article and Find Full Text PDFHereditas
January 2025
Key Laboratory of Reproductive Health Diseases Research and Translation of Ministry of Education & Key Laboratory of Human Reproductive Medicine and Genetic Research of Hainan Provincie & Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, 571101, China.
Background: The dynein cytoplasmic two heavy chain 1 (DYNC2H1) gene encodes a cytoplasmic dynein subunit. Cytoplasmic dyneins transport cargo towards the minus end of microtubules and are thus termed the "retrograde" cellular motor. Mutations in DYNC2H1 are the main causative mutations of short rib-thoracic dysplasia syndrome type III with or without polydactyly (SRTD3).
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