The cDNA that encodes inositol-1,2-cyclic phosphate 2-phosphohydrolase (cyclic hydrolase), an enzyme that converts inositol 1,2-cyclic phosphate (cIns(1,2)P) to inositol 1-phosphate, was expressed in 3T3 cells to investigate the function of inositol cyclic phosphates. Cells with increased cyclic hydrolase activity had lower levels of cIns(1,2)P and grew to a lower density at confluence than control cells. This relationship was strengthened by the demonstration that several cell types with differences in cyclic hydrolase activity had levels of cIns(1,2)P and saturation densities that also correlated inversely with cyclic hydrolase activity. In addition, cyclic hydrolase activity is higher in cells at confluence compared to subconfluence. These results suggest that cellular cIns(1,2)P levels are determined by cyclic hydrolase activity and play a role in the control of cell proliferation.
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Transl Vis Sci Technol
January 2025
STZ eyetrial at the Centre for Ophthalmology, Tuebingen, Germany.
Purpose: Reports of gene therapy-associated retinal atrophies and inflammation have highlighted the importance of preclinical safety assessments of adeno-associated virus (AAV) vector systems. We evaluated in nonhuman primates (NHPs) the ocular safety and toxicology of a novel AAV gene therapy targeting retinitis pigmentosa caused by mutations in PDE6A, which has since been used in a phase I/II clinical trial (NCT04611503).
Methods: A total of 34 healthy cynomolgus animals (Macaca fascicularis) were treated with subretinal injections of rAAV.
PLoS One
January 2025
Division of Oral Physiology, Faculty of Dentistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
This study examined the effects of treadmill running (TR) regimens on craniofacial pain- and anxiety-like behaviors, as well as their effects on neural changes in specific brain regions of male mice subjected to repeated social defeat stress (SDS) for 10 days. Behavioral and immunohistochemical experiments were conducted to evaluate the impact of TR regimens on SDS-related those behaviors, as well as epigenetic and neural activity markers in the anterior cingulate cortex (ACC), insular cortex (IC), rostral ventromedial medulla (RVM), and cervical spinal dorsal horn (C2). Behavioral responses were quantified using multiple tests, while immunohistochemistry measured histone H3 acetylation, histone deacetylases (HDAC1, HDAC2), and neural activity markers (FosB and phosphorylated cAMP response element-binding protein (pCREB).
View Article and Find Full Text PDFEnviron Microbiol
January 2025
Faculty of Biology-Microbiology, University of Freiburg, Freiburg, Germany.
Bacterial degradation of ubiquitous and persistent steroids such as steroid hormones is important for their removal from the environment. Initial studies of steroid degradation in anaerobic bacteria suggested that ring-cleaving hydrolases are involved in oxygen-independent sterane skeleton degradation. However, the enzymes involved in ring A cleavage of the common intermediate androsta-1,4-diene-3,17-dione have remained unknown.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Clinical Division of General Anaesthesia and Intensive Care Medicine, Department of Anesthesia, Genera Intensive Care and Pain Therapy, Medical University Vienna, 1090 Vienna, Austria.
Drug development for human disease relies on preclinical model systems such as human cell cultures and animal experiments before therapeutic treatments can ultimately be tested on humans in clinical studies. We here describe the generation of a novel human cell line (HLMVEC/SVTERT289) that we generated by transfection of microvascular endothelial cells from healthy donor lung tissue with the catalytic domain of telomerase and the SV40 large T/small t-antigen. These cells exhibited satisfactory growth characteristics and largely maintained their native characteristics, including morphology, cell surface marker expression, angiogenic potential and the protein composition of secreted extracellular vesicles.
View Article and Find Full Text PDFBiomolecules
December 2024
Herman B Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Gut peptides, including glucagon-like peptide-1 (GLP-1), regulate metabolic homeostasis and have emerged as the basis for multiple state-of-the-art diabetes and obesity therapies. We previously showed that G protein-coupled receptor 17 (GPR17) is expressed in intestinal enteroendocrine cells (EECs) and modulates nutrient-induced GLP-1 secretion. However, the GPR17-mediated molecular signaling pathways in EECs have yet to be fully deciphered.
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