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Accelerated Endosomal Escape of Splice-Switching Oligonucleotides Enables Efficient Hepatic Splice Correction.
ACS Appl Mater Interfaces
January 2025
Faculty of Life Sciences, Department of Pharmaceutical Sciences, Laboratory of Macromolecular Cancer Therapeutics (MMCT), University of Vienna, Josef-Holaubek-Platz 2, 1090 Vienna, Austria.
Splice-switching oligonucleotides (SSOs) can restore protein functionality in pathologies and are promising tools for manipulating the RNA-splicing machinery. Delivery vectors can considerably improve SSO functionality in vivo and allow dose reduction, thereby addressing the challenges of RNA-targeted therapeutics. Here, we report a biocompatible SSO nanocarrier, based on redox-responsive disulfide cross-linked low-molecular-weight linear polyethylenimine (cLPEI), for overcoming multiple biological barriers from subcellular compartments to en-route serum stability and finally in vivo delivery challenges.
View Article and Find Full Text PDFAge-invariant genes: multi-tissue identification and characterization of murine reference genes.
Aging (Albany NY)
January 2025
Department of Pathology, Yale University School of Medicine, New Haven, CT 06519, USA.
Studies of the aging transcriptome focus on genes that change with age. But what can we learn from age-invariant genes-those that remain unchanged throughout the aging process? These genes also have a practical application: they can serve as reference genes in expression studies. Reference genes have mostly been identified and validated in young organisms, and no systematic investigation has been done across the lifespan.
View Article and Find Full Text PDFBiphasic glucose-stimulated insulin secretion over decades: a journey from measurements and modeling to mechanistic insights.
Life Metab
February 2025
New Cornerstone Science Laboratory, State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, National Biomedical Imaging Center, The Beijing Laboratory of Biomedical Imaging, Peking-Tsinghua Center for Life Sciences, School of Future Technology, Peking University, Beijing 100871, China.
Glucose-stimulated insulin release from pancreatic β-cells is critical for maintaining blood glucose homeostasis. An abrupt increase in blood glucose concentration evokes a rapid and transient rise in insulin secretion followed by a prolonged, slower phase. A diminished first phase is one of the earliest indicators of β-cell dysfunction in individuals predisposed to develop type 2 diabetes.
View Article and Find Full Text PDFClinical evaluation of endoscopic biliary stenting in treatment of malignant obstructive jaundice.
World J Gastrointest Surg
January 2025
Department of General Surgery, Shenzhen University General Hospital, Shenzhen 518000, Guangdong Province, China.
Background: Malignant obstructive jaundice (MOJ) is characterized by the presence of malignant tumors infiltrating or compressing the bile duct, causing poor bile drainage, generalized yellowing, pain, itching, and malaise. MOJ is burdensome for both the society and the families of affected patients and should be taken seriously.
Aim: To evaluate the clinical effect of stent placement during endoscopic retrograde cholangiopancreatography for relieving MOJ and the efficacy of percutaneous transhepatic biliary drainage in terms of liver function improvement, complication rates, and long-term patient outcomes.
Mechanical and functional characterisation of a 3D porous biomimetic extracellular matrix to study insulin secretion from pancreatic β-cell lines.
In Vitro Model
December 2024
Univ. Lille, Inserm, CHU Lille, Institut Pasteur Lille, U1167 - RID-AGE - Facteurs de Risque Et Déterminants Moléculaires Des Maladies Liées Au Vieillissement, F-59000 Lille, France.
Background: Extracellular matrix (ECM) is a three-dimensional (3D) structure found around cells in the tissues of many organisms. It is composed mainly of fibrous proteins, such as collagen and elastin, and adhesive glycoproteins, such as fibronectin and laminin-as well as proteoglycans, such as hyaluronic acid. The ECM performs several essential functions, including structural support of tissues, regulation of cell communication, adhesion, migration, and differentiation by providing biochemical and biomechanical cues to the cells.
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