Although numerous growth factors can promote the regeneration of bone upon parenteral administration, all exhibit undesirable side-effects that prevent their clinical utility. These side-effects arise due to the growth factors' inherent lack of bone affinity. The goal of this study was to develop a means to enhance the bone mineral affinity of osteogenic growth factors so as to minimize their extra-skeletal distribution. Heparin, a glycosaminoglycan that exhibits a high affinity to numerous growth factors, was modified with bisphosphonates to enhance its affinity to bone mineral (i.e. hydroxyapatite, HA). To this end, conjugation of 1-amino-1,1-diphosphonate methane (aminoBP) onto periodate-oxidized heparin using 4-(maleimidomethyl)cyclohexane-1-carboxyl-hydrazide was attempted. Using this chemistry, the number of aminoBPs conjugated onto heparin was modulated by varying the reacting reagent concentrations (to a maximum of 7 aminoBPs per heparin). Increasing the number of aminoBPs resulted in a more than twofold increase in heparin's affinity for HA in vitro. Subsequently, the ability of aminoBP-heparin conjugates to enhance the mineral affinity of basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) was explored. The results revealed that the complexation between the conjugates and growth factors had occurred and that the conjugates increased the bone mineral affinity of bFGF and BMP-2 in an aminoBP-dependent manner. In conclusion, the conjugation of aminoBP onto heparin is a feasible approach to enhance the affinity of heparin-binding, osteogenic growth factors to HA.
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http://dx.doi.org/10.1016/j.jconrel.2004.05.001 | DOI Listing |
Jpn J Clin Oncol
January 2025
Department of Gynecology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
There are many histologic types of gynecologic malignancies. I reviewed three rare ovarian tumor types that have poor prognoses. Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior.
View Article and Find Full Text PDFAgonists of insect hormones, namely molting hormone (MH) and juvenile hormone (JH), disrupt the normal growth of insects and can be employed as insecticides that are harmless to vertebrates. In this study, a series of experiments and computational analyses were conducted to rationally design novel insect hormone agonists. Syntheses and quantitative structure-activity relationship (QSAR) analyses of two MH agonist chemotypes, imidazothiadiazoles and tetrahydroquinolines, revealed that the structural factors important for the ligand-receptor interactions are significantly different between these chemotypes.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2025
School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, China.
Objective: Diabetic neuropathy (DN), a common and debilitating complication of diabetes, significantly impairs the quality of life of affected individuals. While multiple studies have indicated changes in the expression of specific matrix metalloproteinases (MMPs) in patients with DN, and basic research has reported the impact of MMPs on DN, there is a lack of systematic research and the causal relationship remains unclear. The objective of this research is to investigate the casual relationship between MMPs and DN through two-sample Mendelian randomization (MR).
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2025
Reproductive Medicine Center, Sichuan Provincial Women's and Children's Hospital, The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu, China.
Background: Growth hormone (GH) could improve the outcomes of fertilization and embryo transfer (IVF-ET) in patients with decreased ovarian reserve (DOR), but which age group will benefit the most has remained controversial. This study aims to explore the outcome of IVF-ET among differently aged patients with DOR treated with GH.
Methods: A total of 846 patients with DOR undergoing IVF-ET from May 2018 to June 2023 at the Reproductive Medicine Center of Sichuan Provincial Women's and Children's Hospital were prospectively enrolled.
Front Endocrinol (Lausanne)
January 2025
Department of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Medical University, Jinzhou, Liaoning, China.
Objective: The impact of lipid-lowering medications on chronic kidney disease (CKD) remains a subject of debate. This Mendelian randomization (MR) study aims to elucidate the potential effects of lipid-lowering drug targets on CKD development.
Methods: We extracted 11 genetic variants encoding targets of lipid-lowering drugs from published genome-wide association study (GWAS) summary statistics, encompassing LDLR, HMGCR, PCSK9, NPC1L1, APOB, ABCG5/ABCG8, LPL, APOC3, ANGPTL3, and PPARA.
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