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DNA methylation levels may contribute to severe hypertriglyceridemia in multifactorial chylomicronemia syndrome.
Clin Biochem
January 2025
Genetic Dyslipidemias Clinic of the Montreal Clinical Research Institute, Montréal, Québec, Canada; Department of Medicine, Divisions of Experimental Medicine and Medical Biochemistry, McGill University, Montréal, Québec, Canada. Electronic address:
Background And Aims: Familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS) are the two main causes of severe hypertriglyceridemia (sHTG). FCS is a rare autosomal recessive form of sHTG, whereas MCS is mainly polygenic in nature with both common and rare variants accumulating and leading to sHTG. However, 30 to 50% of MCS patients have no identified genetic cause of sHTG.
View Article and Find Full Text PDFDevelopment of an FKBP12-recruiting chemical-induced proximity DNA-encoded library and its application to discover an autophagy potentiator.
Cell Chem Biol
December 2024
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address:
Chemical inducers of proximity (CIPs) are molecules that recruit one protein to another and introduce new functionalities toward modulating protein states and activities. While CIP-mediated recruitment of E3 ligases is widely exploited for the development of degraders, other therapeutic modalities remain underexplored. We describe a non-degrader CIP-DNA-encoded library (CIP-DEL) that recruits FKBP12 to target proteins using non-traditional acyclic structures, with an emphasis on introducing stereochemically diverse and rigid connectors to attach the combinatorial library.
View Article and Find Full Text PDFA patent review of mitogen-activated protein kinase-interacting kinases (MNKs) modulators (2019-present).
Expert Opin Ther Pat
December 2024
Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, China.
Introduction: The mitogen-activated protein kinase interacting kinases (MNKs) modulate protein translation through the phosphorylation of eukaryotic initiation factor 4E (eIF4E) at serine 209, which is crucial for tumorigenesis but dispensable for normal development. MNKs are implicated in various pathological processes, including inflammation, obesity, cancer, etc. Thus, MNKs are considered as potential drug targets and the development of potent and selective MNK inhibitors is a current research focus.
View Article and Find Full Text PDFUnderstanding Vascular Calcification in Chronic Kidney Disease: Pathogenesis and Therapeutic Implications.
Int J Mol Sci
December 2024
Department of Medical and Surgical Sciences, "Magna Grecia" University, 88100 Catanzaro, Italy.
Vascular calcification (VC) is a biological phenomenon characterized by an accumulation of calcium and phosphate deposits within the walls of blood vessels causing the loss of elasticity of the arterial walls. VC plays a crucial role in the incidence and progression of chronic kidney disease (CKD), leading to a significant increase in cardiovascular mortality in these patients. Different conditions such as age, sex, dyslipidemia, diabetes, and hypertension are the main risk factors in patients affected by chronic kidney disease.
View Article and Find Full Text PDFNon-traditional pulmonary function tests in risk stratification of anatomic lung resection: a retrospective review.
Ther Adv Respir Dis
December 2024
Division of Thoracic and Esophageal Surgery, Department of Surgery, University Hospitals Cleveland Medical Center and Case Western Reserve School of Medicine, Cleveland, OH, USA.
Background: Guidelines advocate pulmonary function testing (PFT) in preoperative evaluation before lung resection. Although forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lungs for carbon monoxide (DLCO) are recommended, they are often poor predictors of complications.
Objectives: Determine if PFT testing results other than FEV1 and DLCO are associated with post-operative complications.
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