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Molecules (Basel, Switzerland) Apr 2024Growth hormone deficiency (GHD) and idiopathic short stature (ISS) are the most common types of short stature (SS), but little is known about their pathogenesis, and...
Growth hormone deficiency (GHD) and idiopathic short stature (ISS) are the most common types of short stature (SS), but little is known about their pathogenesis, and even less is known about the study of adolescent SS. In this study, nuclear magnetic resonance (NMR)-based metabolomic analysis combined with least absolute shrinkage and selection operator (LASSO) were performed to identify the biomarkers of different types of SS (including 94 preadolescent GHD (PAG), 61 preadolescent ISS (PAI), 43 adolescent GHD (ADG), and 19 adolescent ISS (ADI)), and the receiver operating characteristic curve (ROC) was further used to evaluate the predictive power of potential biomarkers. The results showed that fourteen, eleven, nine, and fifteen metabolites were identified as the potential biomarkers of PAG, PAI, ADG, and ADI compared with their corresponding controls, respectively. The disturbed metabolic pathways in preadolescent SS were mainly carbohydrate metabolism and lipid metabolism, while disorders of amino acid metabolism played an important role in adolescent SS. The combination of aspartate, ethanolamine, phosphocholine, and trimethylamine was screened out to identify PAI from PAG, and alanine, histidine, isobutyrate, methanol, and phosphocholine gave a high classification accuracy for ADI and ADC. The differences in metabolic characteristics between GHD and ISS in preadolescents and adolescents will contribute to the development of individualized clinical treatments in short stature.
Topics: Adolescent; Humans; Phosphorylcholine; Dwarfism; Lipid Metabolism; Biomarkers; Growth Hormone
PubMed: 38611940
DOI: 10.3390/molecules29071661 -
Colloids and Surfaces. B, Biointerfaces Jun 2024In this work, poly(lactide) nanoparticles were equipped with a bioinspired coating layer based on poly[2-(methacryloyloxy)ethyl phosphorylcholine] and then evaluated...
In this work, poly(lactide) nanoparticles were equipped with a bioinspired coating layer based on poly[2-(methacryloyloxy)ethyl phosphorylcholine] and then evaluated when administered to the lungs and after intravenous injection. Compared to the plain counterparts, the chosen zwitterionic polymer shell prevented the coated colloidal formulation from aggregation and conditioned it for lower cytotoxicity, protein adsorption, complement activation and phagocytic cell uptake. Consequently, no interference with the biophysical function of the lung surfactant system could be detected accompanied by negligible protein and cell influx into the bronchoalveolar space after intratracheal administration. When injected into the central compartment, the coated formulation showed a prolonged circulation half-life and a delayed biodistribution to the liver. Taken together, colloidal drug delivery vehicles would clearly benefit from the investigated poly[2-(methacryloyloxy)ethyl phosphorylcholine]-based polymer coatings.
Topics: Colloids; Animals; Drug Delivery Systems; Phosphorylcholine; Nanoparticles; Polyesters; Mice; Polymers; Tissue Distribution; Lung; Polymethacrylic Acids; Complement Activation; Methacrylates; Humans
PubMed: 38608461
DOI: 10.1016/j.colsurfb.2024.113886 -
Journal of Colloid and Interface Science Jul 2024Humic acids (HA) are ubiquitous in surface waters, leading to significant fouling challenges. While zwitterion-like and zwitterionic surfaces have emerged as promising...
Humic acids (HA) are ubiquitous in surface waters, leading to significant fouling challenges. While zwitterion-like and zwitterionic surfaces have emerged as promising candidates for antifouling, a quantitative understanding of molecular interaction mechanism, particularly at the nanoscale, still remains elusive. In this work, the intermolecular forces between HA and charged, zwitterion-like or zwitterionic monolayers in aqueous environments were quantified using atomic force microscope. Compared to cationic MTAC ([2-(methacryloyloxy)ethyl]trimethylammonium chloride), which exhibited an adhesion energy of ∼1.342 mJ/m with HA due to the synergistic effect of electrostatic attraction and possible cation-π interaction, anionic SPMA (3-sulfopropyl methacrylate) showed a weaker adhesion energy (∼0.258 mJ/m) attributed to the electrostatic repulsion. Zwitterion-like MTAC/SPMA mixture, driven by electrostatic attraction between opposite charges, formed a hydration layer that prevented the interaction with HA, thereby considerably reducing adhesion energy to ∼0.123 mJ/m. In contrast, zwitterionic MPC (2-methacryloyloxyethyl phosphorylcholine) and DMAPS ([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide) displayed ultralow adhesion energy (0.06-0.07 mJ/m) with HA, arising from their strong dipole moments which could induce a tight hydration layer that effectively inhibited HA fouling. The pH-mediated electrostatic interaction resulted in the increased adhesion energy for MTAC but decreased adhesion energy for SPMA with elevated pH, while the adhesion energy for zwitterion-like and zwitterionic surfaces was independent of environmental pH. Density functional theory (DFT) simulation confirmed the strong binding capability of MPC and DMAPS with water molecules (∼-12 kcal mol). This work provides valuable insights into the molecular interaction mechanisms underlying humic-substance-fouling resistance of charged, zwitterion-like and zwitterionic materials at the nanoscale, shedding light on developing more effective strategy for HA antifouling in water treatment.
PubMed: 38603881
DOI: 10.1016/j.jcis.2024.04.038 -
Journal of Nanobiotechnology Apr 2024Dry eye disease (DED) is associated with ocular hyperosmolarity and inflammation. The marketed topical eye drops for DED treatment often lack bioavailability and...
Dry eye disease (DED) is associated with ocular hyperosmolarity and inflammation. The marketed topical eye drops for DED treatment often lack bioavailability and precorneal residence time. In this study, we investigated catechol-functionalized polyzwitterion p(MPC-co-DMA), composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dopamine methacrylamide (DMA) monomers, as potential topical nanotherapeutics for DED. The copolymers were synthesized via random free-radical copolymerization, producing different proportions of catecholic functionalization. All as-prepared polymer compositions displayed good ocular biocompatibility. At a feeding ratio of 1:1, p(MPC-co-DMA) can facilitate a robust mucoadhesion via Michael addition and/or Schiff base reaction, thus prolonging ocular residence time after 4 days of topical instillation. The hydration lubrication of MPC and radical-scavenging DMA endow the nano-agent to ease tear-film hyperosmolarity and corneal inflammation. A single dose of p(MPC-co-DMA) (1 mg/mL) after 4 days post-instillation can protect the cornea against reactive oxygen species, inhibiting cell apoptosis and the over-expression of pro-inflammatory factors (IL-6 and TNF-α). In clinical assessment, DED-induced rabbit eyes receiving p(MPC-co-DMA) could increase lacrimal fluid secretion by 5-fold higher than cyclosporine A. The catechol-functionalized polyzwitterion with enhanced lubricity, mucoadhesion, and anti-oxidation/anti-inflammation properties has shown high promise as a bioactive eye drop formulation for treating DED.
Topics: Animals; Rabbits; Antioxidants; Lubricants; Biocompatible Materials; Anti-Inflammatory Agents; Ophthalmic Solutions; Catechols; Inflammation
PubMed: 38589911
DOI: 10.1186/s12951-024-02448-x -
The Science of the Total Environment Jun 2024Soils represent crucial sinks for pharmaceuticals and microplastics, making them hotspots for pharmaceuticals and plastic pollution. Despite extensive research on the...
Soils represent crucial sinks for pharmaceuticals and microplastics, making them hotspots for pharmaceuticals and plastic pollution. Despite extensive research on the toxicity of pharmaceuticals and microplastics individually, there is limited understanding of their combined effects on soil biota. This study focused on the earthworm Eisenia fetida as test organism to evaluate the biotoxicity and bioaccumulation of the typical pharmaceutical naproxen and microplastics in earthworms. Results demonstrated that high concentrations of naproxen (100 mg kg) significantly increased the malondialdehyde (MDA) content, inducing lipid peroxidation. Even though the low exposure of naproxen exhibits no significant influence to Eisenia fetida, the lipid peroxidation caused by higher concentration than environmental relevant concentrations necessitate attention due to temporal and spatial concentration variability found in the soil environment. Meanwhile, microplastics caused oxidative damage to antioxidant enzymes by reducing the superoxide dismutase (SOD) activity and MDA content in earthworms. Metabolome analysis revealed increased lipid metabolism in naproxen-treated group and reduced lipid metabolism in the microplastic-treated group. The co-exposure of naproxen and microplastics exhibited a similar changing trend to the microplastics-treated group, emphasizing the significant influence of microplastics. The detection of numerous including lipids like 17-Hydroxyandrostane-3-glucuronide, lubiprostone, morroniside, and phosphorylcholine, serves to identify potential biomarkers for naproxen and microplastics exposure. Additionally, microplastics increased the concentration of naproxen in earthworms at sub-organ and subcellular level. This study contributes valuable insights into the biotoxicity and distribution of naproxen and microplastics in earthworms, enhancing our understanding of their combined ecological risk to soil biota.
Topics: Oligochaeta; Naproxen; Animals; Soil Pollutants; Microplastics; Ecotoxicology; Soil; Environmental Monitoring
PubMed: 38583628
DOI: 10.1016/j.scitotenv.2024.172267 -
FASEB Journal : Official Publication of... Apr 2024Vascular calcification is an actively regulated biological process resembling bone formation, and osteogenic differentiation of vascular smooth muscle cells (VSMCs)...
Vascular calcification is an actively regulated biological process resembling bone formation, and osteogenic differentiation of vascular smooth muscle cells (VSMCs) plays a crucial role in this process. 1-Palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC), an oxidized phospholipid, is found in atherosclerotic plaques and has been shown to induce oxidative stress. However, the effects of POVPC on osteogenic differentiation and calcification of VSMCs have yet to be studied. In the present study, we investigated the role of POVPC in vascular calcification using in vitro and ex vivo models. POVPC increased mineralization of VSMCs and arterial rings, as shown by alizarin red staining. In addition, POVPC treatment increased expression of osteogenic markers Runx2 and BMP2, indicating that POVPC promotes osteogenic transition of VSMCs. Moreover, POVPC increased oxidative stress and impaired mitochondria function of VSMCs, as shown by increased ROS levels, impairment of mitochondrial membrane potential, and decreased ATP levels. Notably, ferroptosis triggered by POVPC was confirmed by increased levels of intracellular ROS, lipid ROS, and MDA, which were decreased by ferrostatin-1, a ferroptosis inhibitor. Furthermore, ferrostatin-1 attenuated POVPC-induced calcification of VSMCs. Taken together, our study for the first time demonstrates that POVPC promotes vascular calcification via activation of VSMC ferroptosis. Reducing the levels of POVPC or inhibiting ferroptosis might provide a novel strategy to treat vascular calcification.
Topics: Humans; Muscle, Smooth, Vascular; Phospholipids; Phosphorylcholine; Reactive Oxygen Species; Osteogenesis; Ferroptosis; Vascular Calcification; Myocytes, Smooth Muscle; Cells, Cultured; Cyclohexylamines; Phenylenediamines
PubMed: 38581243
DOI: 10.1096/fj.202302570R -
Antimicrobial Agents and Chemotherapy May 2024Leishmaniasis is a neglected tropical disease infecting the world's poorest populations. Miltefosine (ML) remains the primary oral drug against the cutaneous form of...
Leishmaniasis is a neglected tropical disease infecting the world's poorest populations. Miltefosine (ML) remains the primary oral drug against the cutaneous form of leishmaniasis. The ATP-binding cassette (ABC) transporters are key players in the xenobiotic efflux, and their inhibition could enhance the therapeutic index. In this study, the ability of beauvericin (BEA) to overcome ABC transporter-mediated resistance of to ML was assessed. In addition, the transcription profile of genes involved in resistance acquisition to ML was inspected. Finally, we explored the efflux mechanism of the drug and inhibitor. The efficacy of ML against all developmental stages of in the presence or absence of BEA was evaluated using an absolute quantification assay. The expression of resistance genes was evaluated, comparing susceptible and resistant strains. Finally, the mechanisms governing the interaction between the ABC transporter and its ligands were elucidated using molecular docking and dynamic simulation. Relative quantification showed that the expression of the ABCG sub-family is mostly modulated by ML. In this study, we used BEA to impede resistance of . The IC values, following BEA treatment, were significantly reduced from 30.83, 48.17, and 16.83 µM using ML to 8.14, 11.1, and 7.18 µM when using a combinatorial treatment (ML + BEA) against promastigotes, axenic amastigotes, and intracellular amastigotes, respectively. We also demonstrated a favorable BEA-binding enthalpy to ABC transporter compared to ML. Our study revealed that BEA partially reverses the resistance development of to ML by blocking the alternate ATP hydrolysis cycle.
Topics: Leishmania tropica; ATP-Binding Cassette Transporters; Depsipeptides; Drug Resistance; Molecular Docking Simulation; Antiprotozoal Agents; Phosphorylcholine; Humans; Protozoan Proteins
PubMed: 38572959
DOI: 10.1128/aac.01368-23 -
Langmuir : the ACS Journal of Surfaces... Apr 2024Surface modification of lubricating coatings on biomedical devices is a pivotal strategy to improve the overall performance and clinical efficacy, significantly reducing...
Surface modification of lubricating coatings on biomedical devices is a pivotal strategy to improve the overall performance and clinical efficacy, significantly reducing friction between devices and human tissues and mitigating tissue damage during intervention and long-term implantation. Recently, various hydrophilic polymeric materials have been used for achieving surface functionalization, endowing the biomedical device with excellent superlubrication performance. -Vinylpyrrolidone (NVP) and 2-methacryloyloxyethyl phosphorylcholine (MPC) are two typical representatives of nonionic and zwitterionic materials. However, there is still a research gap in a comparative study of the lubrication mechanisms and properties between them. In this study, a bioinspired and dopamine-assisted codeposition technique was used to fabricate biomimetic hydrophilic coatings, including P(DMA-NVP) and P(DMA-MPC), on polyurethane. To achieve a thorough comparative analysis of the self-adhesive coating performance, 3 M ratios of the copolymers were synthesized and comprehensive material evaluations were conducted. Additionally, surface morphology, hydrophilicity, and lubrication at both the microscale and macroscale were performed. It was found that both hydrophilic coatings exhibited good stability. The P(DMA-MPC) coating, due to the ability to attract and bind a large number of water molecules, demonstrated superior lubrication effects compared to the P(DMA-NVP) coating. The study provides an in-depth understanding of the lubrication behavior of the self-adhesive coatings to enhance the functionality and application in biomedical engineering.
Topics: Humans; Polymers; Resin Cements; Lubrication; Water
PubMed: 38557053
DOI: 10.1021/acs.langmuir.4c00539 -
Colloids and Surfaces. B, Biointerfaces May 2024This study describes the synthesis and characterization of triblock copolymers composed of poly[2-(methacryloyloxy)ethyl phosphorylcholine]-block-poly(propylene...
This study describes the synthesis and characterization of triblock copolymers composed of poly[2-(methacryloyloxy)ethyl phosphorylcholine]-block-poly(propylene glycol)-block-poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PMPC-b-PPG-b-PMPC) intended for, but not limited to, applications in colloidal drug delivery. Atom transfer radical polymerization led to a library of well-defined PMPC-b-PPG-b-PMPC triblock copolymers with varying overall molecular weight (ranging from ∼5 to ∼25 kDa) and composition (weight fraction of the hydrophobic PPG block ranged from ∼10 to ∼50 wt%). The properties of the synthesized triblock copolymers were linked to the PPG to bioinspired PMPC block(s) ratio, where the more hydrophilic species showed adequate aqueous solubility, surface activity and biocompatibility (non-toxicity) in in vitro cell culture. Their amphiphilic nature makes them adsorb efficiently onto polymer nanoparticles, what improves colloidal stability under stress conditions and, furthermore, depletes proteins from unwanted adsorption to the underlying surface. The current findings strengthen our insights into structure-function relationships of PMPC-based coatings leading to protecting shells on relevant polymer nanoparticle formulations. PMPC-b-PPG-b-PMPC triblock copolymers composed of a hydrophobic PPG block of 2-4 kDa flanked by two hydrophilic PMPC blocks each of 5-10 kDa seem to be most promising to enhance colloidal drug delivery vehicles.
Topics: Methacrylates; Phosphorylcholine; Polymers; Drug Delivery Systems; Nanoparticles
PubMed: 38554627
DOI: 10.1016/j.colsurfb.2024.113856 -
International Journal of Molecular... Mar 2024Cardiomyocyte survival is a critical contributing process of host adaptive responses to cardiovascular diseases (CVD). Cells of the cardiovascular endothelium have...
Cardiomyocyte survival is a critical contributing process of host adaptive responses to cardiovascular diseases (CVD). Cells of the cardiovascular endothelium have recently been reported to promote cardiomyocyte survival through exosome-loading cargos. Sphingosylphosphorylcholine (SPC), an intermediate metabolite of sphingolipids, mediates protection against myocardial infarction (MI). Nevertheless, the mechanism of SPC delivery by vascular endothelial cell (VEC)-derived exosomes (VEC-Exos) remains uncharacterized at the time of this writing. The present study utilized a mice model of ischemia/reperfusion (I/R) to demonstrate that the administration of exosomes via tail vein injection significantly diminished the severity of I/R-induced cardiac damage and prevented apoptosis of cardiomyocytes. Moreover, SPC was here identified as the primary mediator of the observed protective effects of VEC-Exos. In addition, within this investigation, in vitro experiments using cardiomyocytes showed that SPC counteracted myocardial I/R injury by activating the Parkin and nuclear receptor subfamily group A member 2/optineurin (NR4A2/OPTN) pathways, in turn resulting in increased levels of mitophagy within I/R-affected myocardium. The present study highlights the potential therapeutic effects of SPC-rich exosomes secreted by VECs on alleviating I/R-induced apoptosis in cardiomyocytes, thereby providing strong experimental evidence to support the application of SPC as a potential therapeutic target in the prevention and treatment of myocardial infarction.
Topics: Mice; Animals; Myocardial Reperfusion Injury; Mitophagy; Myocytes, Cardiac; Myocardial Infarction; Endothelial Cells; Exosomes; Apoptosis; Phosphorylcholine; Sphingosine
PubMed: 38542280
DOI: 10.3390/ijms25063305