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Actas Dermo-sifiliograficas Sep 2022
Topics: Antiprotozoal Agents; Child; Humans; Leishmaniasis, Cutaneous; Phosphorylcholine
PubMed: 36031197
DOI: 10.1016/j.ad.2020.11.033 -
Metabolomics : Official Journal of the... Aug 2023The present work identified and compared intracellular metabolites and metabolic networks in mycelial cultures of Lasiodiplodia theobromae grown under 12 natural light...
INTRODUCTION
The present work identified and compared intracellular metabolites and metabolic networks in mycelial cultures of Lasiodiplodia theobromae grown under 12 natural light and 24 hours' dark using a H NMR-based metabolomics approach.
MATERIALS AND METHODS
Fungal cultures were grown in potato dextrose media, and metabolites were extracted by sonication with sodium phosphate-buffered saline (pH = 6.0, 10% DO, 0.1 mM TSP) from mycelium samples collected every week over four weeks.
RESULTS
Multivariate analyses revealed that the light exposure group showed a positive correlation within beta-hydroxybutyrate, acetoacetate, acetone, betaine, choline, glycerol, and phosphocholine. On the other hand, phenyl acetate, leucine, isoleucine, valine, and tyrosine were positively correlated with dark conditions. Light favored the oxidative degradation of valine, leucine, and isoleucine, leading to the accumulation of choline, phosphocholine, betaine, and ketone bodies (ketogenesis). Ketogenesis, gluconeogenesis, and the biosynthesis of choline, phosphocholine, and betaine, were considered discriminatory routes for light conditions. The light-sensing pathways were interlinked with fungal development, as verified by the increased production of mycelia biomass without fruiting bodies and stress signaling, as demonstrated by the increased production of pigments.
Topics: Metabolomics; Betaine; Phosphorylcholine; Leucine; Isoleucine; Metabolome; Choline; Valine
PubMed: 37580624
DOI: 10.1007/s11306-023-02041-7 -
The Journal of Physical Chemistry. B Nov 2023Improving drug delivery efficiency to solid tumor sites is a central challenge in anticancer therapeutic research. Our previous experimental study (Guo et al., , , 130)...
Improving drug delivery efficiency to solid tumor sites is a central challenge in anticancer therapeutic research. Our previous experimental study (Guo et al., , , 130) showed that soft, elastic liposomes had increased uptake and accumulation in cancer cells and tumors and respectively, relative to rigid particles. As a first step toward understanding how liposomes' molecular structure and composition modulates their elasticity, we performed all-atom and coarse-grained classical molecular dynamics (MD) simulations of lipid bilayers formed by mixing a long-tailed unsaturated phospholipid with a short-tailed saturated lipid with the same headgroup. The former types of phospholipids considered were 1,2-dioleoyl--glycero-3-phosphocholine (DOPC) and 1,2-dipalmitoleoyl--glycero-3-phosphocholine (termed here DPMPC). The shorter saturated lipids examined were 1,2-diheptanoyl--glycero-3-phosphocholine (DHPC), 1,2-didecanoyl--glycero-3-phosphocholine (DDPC), 1,2-dilauroyl--glycero-3-phosphocholine (DLPC), and 1,2-dimyristoyl--glycero-3-phosphocholine (DMPC). Several lipid concentrations and surface tensions were considered. Our results show that DOPC or DPMPC systems having 25-35 mol % of the shortest lipids DHPC or DDPC are the least rigid, having area compressibility moduli that are ∼10% smaller than the values observed in pure DOPC or DPMPC bilayers. These results agree with experimental measurements of the stretching modulus and lysis tension in liposomes with the same compositions. These mixed systems also have lower areas per lipid and form more uneven - interfaces with water, the tails of both primary and secondary lipids are more disordered, and the terminal methyl groups in the tails of the long lipid DOPC or DPMPC wriggle more in the vertical direction, compared to pure DOPC or DPMPC bilayers or their mixtures with the longer saturated lipid DLPC or DMPC. These observations confirm our hypothesis that adding increasing concentrations of the short unsaturated lipid DHPC or DDPC to DOPC or DPMPC bilayers alters lipid packing and thus makes the resulting liposomes more elastic and less rigid. No formation of lipid nanodomains was noted in our simulations, and no clear trends were observed in the lateral diffusivities of the lipids as the concentration, type of secondary lipid, and surface tension were varied.
Topics: Liposomes; Molecular Dynamics Simulation; Dimyristoylphosphatidylcholine; Phosphorylcholine; Phospholipids; Lipid Bilayers; Phosphatidylcholines
PubMed: 37879075
DOI: 10.1021/acs.jpcb.3c04386 -
Biomolecules Jul 2023Adsorbing toxins from the blood to augment membrane-based hemodialysis is an active area of research. Films composed of β-cyclodextrin-co-(methacryloyloxy)ethyl...
Adsorbing toxins from the blood to augment membrane-based hemodialysis is an active area of research. Films composed of β-cyclodextrin-co-(methacryloyloxy)ethyl phosphorylcholine (p(PMβCD-co-MPC)) with various monomer ratios were formed on magnetic nanoparticles and characterized. Surface chemistry effects on protein denaturation were evaluated and indicated that unmodified magnetic nanoparticles greatly perturbed the structure of proteins compared to coated particles. Plasma clotting assays were conducted to investigate the stability of plasma in the presence of particles, where a 2:2 monomer ratio yielded the best results for a given total surface area of particles. Total protein adsorption results revealed that modified surfaces exhibited reduced protein adsorption compared to bare particles, and pure MPC showed the lowest adsorption. Immunoblot results showed that fibrinogen, α1-antitrypsin, vitronectin, prekallikrein, antithrombin, albumin, and C3 correlated with film composition. Hemocompatibility testing with whole blood illustrated that the 1:3 ratio of CD to MPC had a negative impact on platelets, as evidenced by the increased activation, reduced response to an agonist, and reduced platelet count. Other formulations had statistically significant effects on platelet activation, but no formulation yielded apparent adverse effects on hemostasis. For the first time, p(PMβCD-co-MPC)-coated MNP were synthesized and their general hemocompatibility assessed.
Topics: Phosphorylcholine; Magnetite Nanoparticles; Adsorption; Antithrombin III; Blood Coagulation
PubMed: 37627230
DOI: 10.3390/biom13081165 -
Molecular Pharmaceutics Dec 2020Conventional drug solubilization strategies limit the understanding of the full potential of poorly water-soluble drugs during drug screening. Here, we propose a...
Conventional drug solubilization strategies limit the understanding of the full potential of poorly water-soluble drugs during drug screening. Here, we propose a screening approach in which poorly water-soluble drugs are entrapped in poly(2-(methacryloyloxyethyl phosphorylcholine)-poly(2-(diisopropylaminoethyl methacryate) (PMPC-PDPA) polymersomes (POs) to enhance drug solubility and facilitate intracellular delivery. By using a human pediatric glioma cell model, we demonstrated that PMPC-PDPA POs mediated intracellular delivery of cytotoxic and epigenetic drugs by receptor-mediated endocytosis. Additionally, when delivered in combination, drug-loaded PMPC-PDPA POs triggered both an enhanced drug efficacy and synergy compared to that of a conventional combinatorial screening. Hence, our comprehensive synergy analysis illustrates that our screening methodology, in which PMPC-PDPA POs are used for intracellular codelivery of drugs, allows us to identify potent synergistic profiles of anticancer drugs.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Drug Carriers; Drug Screening Assays, Antitumor; Drug Synergism; Endocytosis; Glioma; Humans; Hydrogen-Ion Concentration; Nanoparticles; Phosphorylcholine; Polymethacrylic Acids; Solubility
PubMed: 33175550
DOI: 10.1021/acs.molpharmaceut.0c00791 -
Microbiology Spectrum Aug 2023Many bacterial surface proteins and carbohydrates are modified with phosphorylcholine (ChoP), which contributes to host mimicry and can also promote colonization and...
Analysis of Bacterial Phosphorylcholine-Related Genes Reveals an Association between Type-Specific Biosynthesis Pathways and Biomolecules Targeted for Phosphorylcholine Modification.
Many bacterial surface proteins and carbohydrates are modified with phosphorylcholine (ChoP), which contributes to host mimicry and can also promote colonization and survival in the host. However, the ChoP biosynthetic pathways that are used in bacterial species that express ChoP have not been systematically studied. For example, the well-studied Lic-1 pathway is absent in some ChoP-expressing bacteria, such as Neisseria meningitidis and Neisseria gonorrhoeae. This raises a question as to the origin of the ChoP used for macromolecule biosynthesis in these species. In the current study, we used analyses to identify the potential pathways involved in ChoP biosynthesis in genomes of the 26 bacterial species reported to express a ChoP-modified biomolecule. We used the four known ChoP biosynthetic pathways and a ChoP transferase as search terms to probe for their presence in these genomes. We found that the Lic-1 pathway is primarily associated with organisms producing ChoP-modified carbohydrates, such as lipooligosaccharide. Pilin phosphorylcholine transferase A (PptA) homologs were detected in all bacteria that express ChoP-modified proteins. Additionally, ChoP biosynthesis pathways, such as phospholipid -methyltransferase (PmtA), phosphatidylcholine synthase (Pcs), or the acylation-dependent phosphatidylcholine biosynthesis pathway, which generate phosphatidylcholine, were also identified in species that produce ChoP-modified proteins. Thus, a major finding of this study is the association of a particular ChoP biosynthetic pathway with a cognate, target ChoP-modified surface factor; i.e., protein versus carbohydrate. This survey failed to identify a known biosynthetic pathway for some species that express ChoP, indicating that a novel ChoP biosynthetic pathway(s) may remain to be identified. The modification of bacterial surface virulence factors with phosphorylcholine (ChoP) plays an important role in bacterial virulence and pathogenesis. However, the ChoP biosynthetic pathways in bacteria have not been fully understood. In this study, we used analysis to identify potential ChoP biosynthetic pathways in bacteria that express ChoP-modified biomolecules and found the association between a specific ChoP biosynthesis pathway and the cognate target ChoP-modified surface factor.
Topics: Phosphorylcholine; Biosynthetic Pathways; Bacterial Proteins; Fimbriae Proteins; Transferases
PubMed: 37436144
DOI: 10.1128/spectrum.01583-23 -
Langmuir : the ACS Journal of Surfaces... Mar 2022Enhancing the lubrication property and bacterial resistance is extremely important for interventional biomedical implants to avoid soft tissue damage and biofilm...
Enhancing the lubrication property and bacterial resistance is extremely important for interventional biomedical implants to avoid soft tissue damage and biofilm formation. In this study, a zwitterionic phosphorylcholine coating (PMPC) was successfully developed to achieve surface functionalization of a polyurethane (PU)-based ureteral stent via subsurface "grafting from" photopolymerization. Typical surface characterizations such as Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and surface wettability and morphology analyses examined by scanning electron microscopy, atomic force microscopy, and transmission electron microscopy demonstrated that the phosphorylcholine polymer was grafted on the substrate with a thickness of 180 nm. Additionally, the tribological experiment performed by a universal material tester showed that the lubrication performance of PU-PMPC was significantly improved compared with that of PU. The experiments indicated that the PMPC coating was biocompatible and stably modified on the surface of the substrate with an excellent bacterial resistance rate of >90%. Furthermore, the result of the experiment showed that the anti-encrustation performance of the surface-functionalized ureteral stent was better than that of the bare ureteral stent. The great enhancement in the lubrication, bacterial resistance, and anti-encrustation properties of the phosphorylcholine coating was thought to be due to the hydration effects of the zwitterionic charges. In summary, the bioinspired zwitterionic phosphorylcholine coating developed herein achieved significantly improved lubrication, bacterial resistance, and anti-encrustation performances and could be used as a convenient approach for surface functionalization of interventional biomedical implants.
Topics: Lubrication; Phosphorylcholine; Polyurethanes; Surface Properties; Wettability
PubMed: 35266725
DOI: 10.1021/acs.langmuir.2c00263 -
Frontiers in Cellular and Infection... 2021and species are filamentous fungi responsible for a wide range of infections in humans and are frequently associated with cystic fibrosis and immunocompromising...
and species are filamentous fungi responsible for a wide range of infections in humans and are frequently associated with cystic fibrosis and immunocompromising conditions. Because they are usually resistant to many antifungal drugs available in clinical settings, studies of alternative targets in fungal cells and therapeutic approaches are necessary. In the present work, we evaluated the antifungal activity of miltefosine against and species and how this phospholipid analogue affects the fungal cell. Miltefosine inhibited different and species at 2-4 µg/ml and reduced biofilm formation. The loss of membrane integrity in caused by miltefosine was demonstrated by leakage of intracellular components and lipid raft disorganisation. The exogenous addition of glucosylceramide decreased the inhibitory activity of miltefosine. Reactive oxygen species production and mitochondrial activity were also affected by miltefosine, as well as the susceptibility to fluconazole, caspofungin and myoricin. The data obtained in the present study contribute to clarify the dynamics of the interaction between miltefosine and and cells, highlighting its potential use as new antifungal drug in the future.
Topics: Antifungal Agents; Ascomycota; Humans; Microbial Sensitivity Tests; Phosphorylcholine; Scedosporium
PubMed: 34368017
DOI: 10.3389/fcimb.2021.698662 -
International Journal of Molecular... May 2022Lipid structural diversity strongly affects biomembrane chemico-physical and structural properties in addition to membrane-associated events. At high concentrations,...
Lipid structural diversity strongly affects biomembrane chemico-physical and structural properties in addition to membrane-associated events. At high concentrations, cholesterol increases membrane order and rigidity, while polyunsaturated lipids are reported to increase disorder and flexibility. How these different tendencies balance in composite bilayers is still controversial. In this study, electron paramagnetic resonance spectroscopy, small angle neutron scattering, and neutron reflectivity were used to investigate the structural properties of cholesterol-containing lipid bilayers in the fluid state with increasing amounts of polyunsaturated omega-3 lipids. Either the hybrid 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine or the symmetric 1,2-docosahexaenoyl-sn-glycero-3-phosphocholine were added to the mixture of the naturally abundant 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine and cholesterol. Our results indicate that the hybrid and the symmetric omega-3 phospholipids affect the microscopic organization of lipid bilayers differently. Cholesterol does not segregate from polyunsaturated phospholipids and, through interactions with them, is able to suppress the formation of non-lamellar structures induced by the symmetric polyunsaturated lipid. However, this order/disorder balance leads to a bilayer whose structural organization cannot be ascribed to either a liquid ordered or to a canonical liquid disordered phase, in that it displays a very loose packing of the intermediate segments of lipid chains.
Topics: Cholesterol; Fatty Acids, Omega-3; Lipid Bilayers; Phospholipids; Phosphorylcholine
PubMed: 35628128
DOI: 10.3390/ijms23105322 -
Fish Physiology and Biochemistry Oct 2022Changes in the metabolic profile within the intestine of lenok (Brachymystax lenok) when challenged to acute and lethal heat stress (HS) are studied using no-target...
Changes in the metabolic profile within the intestine of lenok (Brachymystax lenok) when challenged to acute and lethal heat stress (HS) are studied using no-target HPLC-MS/MS metabonomic analysis. A total of 51 differentially expressed metabolites (VIP > 1, P < 0.05) were identified in response to HS, and 34 occurred in the positive ion mode and 17 in negative ion mode, respectively. After heat stress, changes in metabolites related to glycolysis (i.e., alpha-D-glucose, stachyose, and L-lactate) were identified. The metabolites (acetyl carnitine, palmitoylcarnitine, carnitine, and erucic acid) related to fatty acid β-oxidation accumulated significantly, and many amino acids (L-tryptophan, D-proline, L-leucine, L-phenylalanine, L-aspartate, L-tyrosine, L-methionine, L-histidine, and L-glutamine) were significantly decreased in HS-treated lenok. The mitochondrial β-oxidation pathway might be inhibited, while severe heat stress might activate the anaerobic glycolysis and catabolism of amino acid for energy expenditure. Oxidative damage in HS-treated lenok was indicated by the decreased glycerophospholipid metabolites (i.e., glycerophosphocholine, 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine, 1-palmitoyl-sn-glycero-3-phosphocholine, 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine, and 1, 2-dioleoyl-sn-glycero-3-phosphatidylcholine) and the increased oxylipin production (12-HETE and 9R, 10S-EpOME). The minor oxidative pathways (omega-oxidation and peroxisomal beta-oxidation) were likely to be induced in HS-treated lenok.
Topics: Animals; Erucic Acids; Palmitoylcarnitine; Glutamine; Acetylcarnitine; Aspartic Acid; Leucine; Tryptophan; Histidine; Oxylipins; 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Phosphorylcholine; Tandem Mass Spectrometry; Salmonidae; Phosphatidylcholines; Heat-Shock Response; Intestines; Methionine; Proline; Tyrosine; Phenylalanine; Glucose; Lactates
PubMed: 36169784
DOI: 10.1007/s10695-022-01128-7