ABSTRACT
Excessive reactive oxygen species (ROS) in the microenvironment of osteoporosis (OP) not only accelerate the bone absorption, but also affect the osteogenic and mineralized effect of osteoblasts. Procyanidins (PC) have been reported to have anti-oxidation effects, but low bioavailability. This study aimed to explore the effect of magnesium oxide nanoparticles (MgO-PC NPs)-loaded PC on the osteogenesis and mineralization of osteoblasts that stimulated by H2O2. PC was loaded onto MgO NPs and characterized by transmission electron microscopy, energy dispersive spectroscopy, dynamic light scattering, and Fourier transform infrared spectroscopy. After primary screening by cytotoxicity assay, MgO-PC NPs containing 20 µM of PC were chosen for further studies. In H2O2-stimulated osteoblasts, dichlorodihydrofluorescein diacetate probe, Cell Counting Kit-8, quantitative real-time polymerase chain reaction, alkaline phosphatase staining/activity and Alizarin red staining were used to detect the ROS production, cell viability and osteogenic and mineralized markers of osteoblasts. PC was loaded onto MgO NPs to successfully receive MgO-PC NPs with a diameter of about 144 nm and negative potential. PC can sustain release from MgO-PC NPs for at least 16 d. The controlled release of PC from MgO-PC NPs can effectively eliminate ROS and thereby promoted the cell activity. Most importantly, the osteogenesis and mineralization of osteoblasts under oxidative stress were also significantly reversed by MgO-PC NPS. Thus, these findings indicate that MgO-PC NPs may be developed as a potential therapeutic strategy for OP.
Subject(s)
Biflavonoids , Catechin , Cell Survival , Hydrogen Peroxide , Magnesium Oxide , Nanoparticles , Osteoblasts , Osteogenesis , Oxidative Stress , Proanthocyanidins , Reactive Oxygen Species , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteoblasts/cytology , Proanthocyanidins/pharmacology , Proanthocyanidins/chemistry , Catechin/chemistry , Catechin/pharmacology , Oxidative Stress/drug effects , Magnesium Oxide/chemistry , Reactive Oxygen Species/metabolism , Animals , Cell Survival/drug effects , Biflavonoids/pharmacology , Biflavonoids/chemistry , Osteogenesis/drug effects , Hydrogen Peroxide/chemistry , Nanoparticles/chemistry , Delayed-Action Preparations/chemistry , Mice , Calcification, Physiologic/drug effects , Spectroscopy, Fourier Transform InfraredABSTRACT
PURPOSE: Transient pregnancy-induced Cushing's syndrome is a rare condition characterized by the manifestation of symptoms solely during pregnancy, which typically resolve spontaneously following delivery or miscarriage. While it has been established that GNAS is associated with adrenal tumors, its specific role in the pathogenesis of pregnancy-induced Cushing's syndrome remains uncertain.This work aims to examine the association between GNAS mutation and pregnancy-induced Cushing's syndrome. METHODS: DNA was extracted from patients' peripheral blood and tumor tissues for whole-exome sequencing (WES) and Sanger sequencing. We used AlphaFold to predict the protein structure of wild-type and mutant GNAS and to make functional predictions, and immunohistochemistry was used to detect disease-associated protein expression. A review and summary of reported cases of transient pregnancy-induced Cushing's syndrome induced by pregnancy was conducted. RESULTS: Using WES, we identified a somatic mutation in GNAS (NM_000516, c.C601T, p.R201C) that was predicted to have a deleterious effect using computational methods, such as AlphaFold. Human chorionic gonadotropin (hCG) stimulation tests had weakly positive results, and immunohistochemical staining of adrenal adenoma tissue also revealed positivity for luteinizing hormone/chorionic gonadotropin receptor (LHCGR) and cytochrome P450 family 11 subfamily B member 1 (CYP11B1). We reviewed 15 published cases of transient Cushing's syndrome induced by pregnancy. Among these cases, immunohistochemical staining of the adrenal gland showed positive LHCGR expression in 3 case reports, similar to our findings. CONCLUSION: Transient pregnancy-induced Cushing's syndrome may be associated with somatic GNAS mutations and altered adrenal pathology due to abnormal activation of LHCGR.
Subject(s)
Cushing Syndrome , Female , Pregnancy , Humans , Cushing Syndrome/diagnosis , Receptors, LH/genetics , Receptors, LH/metabolism , Luteinizing Hormone/metabolism , Chorionic Gonadotropin , Mutation , Hydrocortisone , Chromogranins/genetics , GTP-Binding Protein alpha Subunits, Gs/geneticsABSTRACT
Nanogenerators capable of harvesting energy from environmental mechanical energy are attractive for many applications. In this paper, we present a simple, low-cost approach to convert low-frequency mechanical energy into electric power using piezoelectric ZnO nanorods grown on a common paper substrate. This energy conversion device has ultrahigh flexibility and piezoelectric sensitivity and can produce an output voltage of up to 10 mV and an output current of about 10 nA. It is demonstrated that the device's electric output behavior can be optionally changed between four types of mode simply by controlling the straining rate. Furthermore, it is also shown that the electric output can be enhanced by scaling the size of the device. This energy-harvesting technology provides a simple and cost-effective platform to capture low-frequency mechanical energy, such as body movements, for practical applications.
