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MFN2-mediated decrease in mitochondria-associated endoplasmic reticulum membranes contributes to sunitinib-induced endothelial dysfunction and hypertension.
J Mol Cell Cardiol
January 2025
Department of Cardiology, Harbin Medical University Cancer Hospital, NHC Key Laboratory of Cell Transplantation, Department of Cardiology, Central Laboratory, The First Affiliated Hospital of Harbin Medical University, Institute of Metabolic Disease, Heilongjiang Academy of Medical Sciences, Heilongjiang Key Laboratory for Metabolic Disorder & Cancer Related Cardiovascular Diseases, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Harbin, China. Electronic address:
Unlabelled: Treatment of cancer patients with tyrosine kinase inhibitors (TKIs) often results in hypertension, but the underlying mechanism remains unclear. This study aimed to examine the role of mitochondrial morphology and function, particularly mitochondria-associated endoplasmic reticulum membranes (MAMs), in sunitinib-induced hypertension.
Methods: Both in vitro and in vivo experiments performed to assesse reactive oxygen species (ROS), nitric oxide (NO), endothelium-dependent vasorelaxation, systemic blood pressure, and mitochondrial function in human umbilical vein endothelial cells (HUVECs) and C57BL/6 mouse aortic endothelial cells, under vehicle or sunitinib treatment condition.
Regulating astrocyte phenotype by Lcn2 inhibition toward ischemic stroke therapy.
Biomaterials
January 2025
Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu, 610031, PR China.
Astrocytes can be reacted to "reactive astrocytes" after ischemia-reperfusion injury, in which A1 phenotype causes neuronal and oligodendrocyte death, whereas the A2 phenotype exerts neuroprotective effects, thus regulating reactive astrocyte to A2 type is a potential target for stroke therapy. Lcn2 level is highly associated with the phenotypic polarization of astrocytes. We found that silencing the Lcn2 gene by adeno-associated virus (AAV)-Lcn2 shRNA adenovirus resulted in a dramatic decrease in A1-type astrocytes and increase in A2 astrocytes in MCAO mice.
View Article and Find Full Text PDFBetagenin ameliorates diabetes by inducing insulin secretion and β-cell proliferation.
J Biol Chem
January 2025
Division of Experimental Animal, Hidaka Branch, Biomedical Research Center, Saitama Medical University, Saitama, Japan; Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan. Electronic address:
Recent success with the use of glucagon-like peptide-1 (GLP-1) receptor analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of patients with diabetes has highlighted the role of the intestine as an endocrine organ. Gut-derived hormones, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and ghrelin, have important roles in the control of energy metabolism and food intake, and are associated with the metabolic syndrome. In this study, we isolated and identified a new intestine-derived hormone, betagenin, and showed that it stimulates insulin secretion and β-cell proliferation and suppresses β-cell apoptosis.
View Article and Find Full Text PDFEffectiveness and Safety of Adalimumab in Patients With Very Early-Onset Inflammatory Bowel Disease: A Retrospective Study on Behalf of the Porto Inflammatory Bowel Disease Working Group of European Society for Pediatric Gastroenterology Hepatology and Nutrition.
Inflamm Bowel Dis
January 2025
Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petach Tikva 4920235, Israel.
Background And Aims: Patients with very early-onset inflammatory bowel disease (VEO-IBD), with an age of onset < 6 years, can present with severe manifestations and may require biologic therapy. Infliximab and adalimumab are approved for induction and maintenance in pediatric IBD patients but are licensed only above the age of 6 years. Effectiveness and safety data on adalimumab in this patient population are lacking.
View Article and Find Full Text PDFConventional and Tropism-Modified High-Capacity Adenoviral Vectors Exhibit Similar Transduction Profiles in Human iPSC-Derived Retinal Organoids.
Int J Mol Sci
December 2024
Department of Ophthalmology, Leiden University Medical Center (LUMC), Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Viral vector delivery of gene therapy represents a promising approach for the treatment of numerous retinal diseases. Adeno-associated viral vectors (AAV) constitute the primary gene delivery platform; however, their limited cargo capacity restricts the delivery of several clinically relevant retinal genes. In this study, we explore the feasibility of employing high-capacity adenoviral vectors (HC-AdVs) as alternative delivery vehicles, which, with a capacity of up to 36 kb, can potentially accommodate all known retinal gene coding sequences.
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