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Epithelial ovarian cancer (EOC) is a common gynecological cancer with high mortality rates. The main objective of this study was to investigate the serum amino acid and organic acid profiles to distinguish key metabolites for screening EOC patients. In total, 39 patients with EOC and 31 healthy controls were selected as the training set. Serum amino acid and organic acid profiles were determined using the targeted metabolomics approach. Metabolite profiles were processed via multivariate analysis to identify potential metabolites and construct a metabolic network. Finally, a test dataset derived from 29 patients and 28 healthy controls was constructed to validate the potential metabolites. Distinct amino acid and organic acid profiles were obtained between EOC and healthy control groups. Methionine, glutamine, asparagine, glutamic acid and glycolic acid were identified as potential metabolites to distinguish EOC from control samples. The areas under the curve for methionine, glutamine, asparagine, glutamic acid and glycolic acid were 0.775, 0 778, 0.955, 0.874 and 0.897, respectively, in the validation study. Metabolic network analysis of the training set indicated key roles of alanine, aspartate and glutamate metabolism as well as D-glutamine and D-glutamate metabolism in the pathogenesis of EOC. Amino acid and organic acid profiles may serve as potential screening tools for EOC. Data from this study provide useful information to bridge gaps in the understanding of the amino acid and organic acid alterations associated with epithelial ovarian cancer. Amino acid and organic acid profiles may serve as potential screening tools for EOC. Data from this study provide useful information to bridge gaps in the understanding of the amino acid and organic acid alterations associated with epithelial ovarian cancer.Cardiovascular disease (CVD) is still one of the most significant diseases and is a considerable threat to human health globally. PIWI-interacting RNAs (piRNAs) are novel small noncoding RNAs (ncRNAs) traditionally considered to be specifically expressed in the germline of many animal species and involved in the maintenance of germline stem cells and spermatogenesis. Although little is known about the origin and action of piRNAs and PIWI proteins in somatic cells, these molecules are emerging as readily available biomarkers for the diagnosis and treatment of cardiac injury and multiform CVD. Accumulating evidence reveals that piRNAs and PIWI proteins are associated with some molecular and cellular pathways in CVD. Here, we summarize recent evidence and evaluate the molecular mechanism of the involvement of piRNAs and PIWI proteins in CVD.Extracellular vesicles (EVs) are membrane-enclosed particles, heterogeneous in size, shape, contents, biogenesis and structure. They are released by eukaryotic and prokaryotic cells and exert (patho-)physiological roles as mediators for transmitting molecular information from the producer (donor) to a recipient cell. This review focuses on the potential of EVs for delivering nucleic acids, as particularly problematic cargoes with regard to stability/protection and uptake efficacy. It highlights important properties of EVs for nucleic acid delivery and discusses their physiological and pathophysiological roles with regard to various cellular RNA species. It then describes the application of EVs for delivering a broad selection of nucleic acids/oligonucleotides, in particular giving a comprehensive overview of preclinical in vivo studies and the various strategies explored. In this context, different techniques for EV loading are discussed, as well as other important technical aspects related to EV preparation, characterization and in particular, the various approaches of artificial EV modification.Most anticancer drugs are not orally bioavailable due to their undesirable physicochemical properties and inherent physiological barriers. In this study, a polymeric prodrug strategy was presented to enhance the oral bioavailability of BCS class IV drugs using paclitaxel (PTX) as the model drug. PTX was covalently conjugated with cholic acid-functionalized PEG by a redox-sensitive disulfide bond. https://www.selleckchem.com/products/monocrotaline.html Cholic acid-functionalized PEGylated PTX (CPP) achieved remarkably improved PTX solubility (>30,000-fold), as well as favorable stability under the physiological environment and controlled drug release in the tumor. Meanwhile, CPP could self-assemble into nanoparticles with an average size of 56.18 ± 2.06 nm and drug loading up to 17.6% (w/w). Then, permeability study on Caco-2 cell monolayers demonstrated that CPP obtained an approximately 4-fold increase by apical sodium-dependent bile acid transporter (ASBT) mediated transport, compared with Taxol®. Pharmacokinetic studies carried out in rats confirmed that the oral bioavailability of CPP was 10-fold higher than that of Taxol®. Finally, significant improvement in the antitumor efficacy of CPP against breast cancer was confirmed on MDA-MB-231 cells. In summary, this prodrug-based cascade strategy offers new ways for chemotherapeutic drugs whose oral delivery is limited by solubility and permeability, also endows drugs with the capacity of tumor-specific release.This work aimed to investigate skin permeation profiles of chiral flurbiprofen and clarify the molecular mechanism of transdermal permeation difference of enantiomers. The in vitro transdermal permeation of enantiomers through rat skin was studied by diffusion cells. Physicochemical parameters of model chiral drugs were determined. Molecular interaction between chiral flurbiprofen and ceramides of skin was investigated by FTIR, 13C NMR and molecular docking. The skin permeation mechanism of chiral drugs was characterized by ATR-FTIR, Raman spectra, DSC and molecular dynamic simulation. The results showed that the amount of the permeation and retention amount of (S)-flurbiprofen was 1.5 times over that of (R)-flurbiprofen. And it was proven that the difference was not induced by physicochemical properties but the molecular interaction between drug-skin components. (S)-flurbiprofen was easy to form stronger hydrogen bonding with -CONH group of skin lipids due to its steric configuration, which disturbed lipids arrangement more easily according to the results of ATR-FTIR (ΔνasCH2 = 1.
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