The inhibitory effects of N-(4-hydroxyphenyl) retinamide and its glucuronide derivative on the development and growth of 7,12-dimethylbenz (a) anthracene - induced rat mammary tumors in vivo were compared. The results indicate that the glucuronide had a greater chemopreventive potency than equimolar concentration of the free retinoid by all the criteria measured, mainly the inhibition of tumor incidence, multiplicity and tumor growth. HPLC analysis of the blood of the rats showed no hydrolysis of the glucuronide during its chronic consumption, indicating that the retinoid glucuronide is probably acting in vivo per se rather than through hydrolysis to the free retinoid. The higher potency and lower toxicity of the glucuronide suggests, for the first time, that the conjugate may have an in vivo chemopreventive advantage over the parent retinamide.
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J Bone Miner Res
January 2025
Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD.
Growth-plate (GP) injures in limbs and other sites can impair GP function and cause deceleration of bone growth, leading to progressive bone lengthening imbalance, deformities and/or physical discomfort, decreased motion and pain. At present, surgical interventions are the only means available to correct these conditions by suppressing the GP activity in the unaffected limb and/or other bones in the ipsilateral region. Here, we aimed to develop a pharmacologic treatment of GP growth imbalance that involves local application of nanoparticles-based controlled release of a selective retinoic acid nuclear receptor gamma (RARγ) agonist drug.
View Article and Find Full Text PDFCurr Top Dev Biol
January 2025
Department of Pharmaceutics, School of Pharmacy, University of Washington.
The active metabolite of vitamin A, all-trans-retinoic acid (atRA), is critical for maintenance of many cellular processes. Although the enzymes that can synthesize and clear atRA in mammals have been identified, their tissue and cell-type specific roles are still not fully established. Based on the plasma protein binding, tissue distribution and lipophilicity of atRA, atRA partitions extensively to lipid membranes and other neutral lipids in cells.
View Article and Find Full Text PDFCurr Top Dev Biol
January 2025
Development, Aging, and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States. Electronic address:
All-trans RA (ATRA) is a small molecule derived from retinol (vitamin A) that directly controls gene expression at the transcriptional level by serving as a ligand for nuclear ATRA receptors. ATRA is produced by ATRA-generating enzymes that convert retinol to retinaldehyde (retinol dehydrogenase; RDH10) followed by conversion of retinaldehyde to ATRA (retinaldehyde dehydrogenase; ALDH1A1, ALDH1A2, or ALDH1A3). Determining what ATRA normally does during vertebrate development has been challenging as studies employing ATRA gain-of-function (RA treatment) often do not agree with genetic loss-of-function studies that remove ATRA via knockouts of ATRA-generating enzymes.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India. Electronic address:
Histone deacetylases (HDACs) play a critical role in chromatin remodelling and modulating the activity of various histone proteins. Aberrant HDAC functions has been related to the progression of breast cancer (BC), making HDAC inhibitors (HDACi) promising small-molecule therapeutics for its treatment. Hydroxamic acid (HA) is a significant pharmacophore due to its strong metal-chelating ability, HDAC inhibition properties, MMP inhibition abilities, and more.
View Article and Find Full Text PDFStem Cell Res Ther
January 2025
Department of Cell Biology and Histology, University of the Basque Country UPV/EHU, Leioa, Bizkaia, 48940, Spain.
Background And Aim: Human dental pulp stem cells (hDPSCs) constitute a promising alternative for central nervous system (CNS) cell therapy. Unlike other human stem cells, hDPSCs can be differentiated, without genetic modification, to neural cells that secrete neuroprotective factors. However, a better understanding of their real capacity to give rise to functional neurons and integrate into synaptic networks is still needed.
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