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Scientific Reports Oct 2021Obesity associates with reduced life expectancy, type 2 diabetes, hypertension and cardiovascular disease, and is characterized by chronic inflammation.... (Comparative Study)
Comparative Study Observational Study
Obesity associates with reduced life expectancy, type 2 diabetes, hypertension and cardiovascular disease, and is characterized by chronic inflammation. Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein, dead cells and some microorganisms. Antibodies against PC (anti-PC) have anti-inflammatory properties. Here, we explored the role of anti-PC in hospitalized versus non-hospitalized obese. One-hundred-and-twenty-eight obese (BMI ≥ 30 kg/m) individuals (59.8 (± 5.5) years, 53.9% women) from the Malmö Diet and Cancer Cardiovascular Cohort were examined and IgM, IgG1 and IgG2 anti-PC were analyzed by ELISA. Individuals with at least one recorded history of hospitalization prior to study baseline were considered hospitalized obese (HO). Associations between IgM, IgG1 and IgG2 anti-PC and HO (n = 32)/non-hospitalized obese (NHO) (n = 96), but also with metabolic syndrome and diabetes were analysed using logistic regressions. Both IgM and IgG1 anti-PC were inversely associated with HO, also after controlling for age and sex. When further adjusted for waist circumference, systolic blood pressure, glucose levels and smoking status, only IgG1 anti-PC remained significantly associated with HO. In multivariate models, each 1 standard deviation of increment in anti-PC IgG1 levels was inversely associated with prevalence of HO (odds ratio 0.57; CI 95% 0.33-0.98; p = 0.044). IgG2 anti-PC did not show any associations with HO. Low levels of IgM and IgG1 anti-PC are associated with higher risk of being a HO individual independent of sex and age, IgG1 anti-PC also independently of diabetes and metabolic syndrome. The anti-inflammatory properties of these antibodies may be related to inflammation in obesity and its complications.
Topics: Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Hospitalization; Humans; Immunoglobulin G; Immunoglobulin M; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Obesity; Phosphorylcholine; Risk Factors
PubMed: 34642415
DOI: 10.1038/s41598-021-99615-z -
The Journal of Prosthetic Dentistry Jan 2023Polymethyl methacrylate (PMMA) is commonly used in dentistry, including as a denture base material. However, the colonization of a PMMA surface by microbial...
STATEMENT OF PROBLEM
Polymethyl methacrylate (PMMA) is commonly used in dentistry, including as a denture base material. However, the colonization of a PMMA surface by microbial microorganisms could increase the risk of oral diseases such as denture stomatitis and gingivitis. The development of PMMA with antibacterial properties should improve its clinical application, but whether adding ε-poly-L-lysine (ε-PL) and 2-methacryloyloxyethyl phosphorylcholine (MPC) provides antimicrobial effects is unclear.
PURPOSE
This in vitro study aimed to develop a novel antibacterial PMMA resin containing the natural nontoxic antibacterial agent ε-PL and the protein repellent agent MPC. The mechanical properties, protein repellency, and antimicrobial activities of the resin were then evaluated.
MATERIAL AND METHODS
Different mass fractions of ε-PL and MPC were mixed into PMMA as the experimental groups, with unaltered PMMA as the control group. The flexural strength (n=10) and surface roughness (n=6) of the resulting mixtures were measured to determine their mechanical properties. The antiprotein properties were measured by using the micro bicinchoninic acid method (n=6). The antimicrobial effect of the resin was assessed using live/dead staining (n=6) and methyltransferase (MTT) assays (n=10). According to the variance homogeneity and normal distribution results, 1-way analysis of variance followed by the Tukey honestly significant difference test or the Welch test and the Games-Howell test were used (α=.05 for all tests).
RESULTS
No significant differences were found in the flexural strength values and surface roughness of the specimens containing 1.5% MPC and 1.5% ε-PL compared with those of the control (P>.05). The addition of ε-PL to the PMMA resin alone significantly increased its bactericidal properties (P<.05). Adding both ε-PL and MPC further increased the antibacterial activity of the PMMA resin without increasing protein adhesion more than in the control group.
CONCLUSIONS
The incorporation of both ε-PL and MPC into PMMA improved its antibacterial capacity without affecting its mechanical properties and did not increase protein adhesion. Therefore, the novel PMMA fabricated in this study shows promise for dental applications.
Topics: Polymethyl Methacrylate; Polylysine; Anti-Bacterial Agents; Methacrylates; Phosphorylcholine; Materials Testing; Denture Bases; Surface Properties
PubMed: 36476985
DOI: 10.1016/j.prosdent.2022.11.009 -
European Journal of Medicinal Chemistry Dec 2019This mini-review focuses on leishmanicidal drugs that were sourced from small molecules previously approved for other diseases. The mechanisms of action of these... (Review)
Review
This mini-review focuses on leishmanicidal drugs that were sourced from small molecules previously approved for other diseases. The mechanisms of action of these molecules are herein explored, to probe the origins of their inter-species growth inhibitory activities. It is shown how the transversal action of the azoles - fluconazole, posaconazole and itraconazole - in both fungi and Leishmania is due to the occurrence of the same target, lanosterol 14-α-demethylase, in these two groups of species. In turn, the drugs miltefosine and amphotericin B are presented as truly multi-target agents, acting on small molecules, proteins, genes and even organelles. Steps towards future leishmanicidal drug candidates based on the multi-target strategy and on drug repurposing are also briefly presented.
Topics: Amphotericin B; Antifungal Agents; Drug Repositioning; Drug Resistance, Fungal; Fluconazole; Humans; Itraconazole; Leishmaniasis; Molecular Targeted Therapy; Phosphorylcholine; Sterol 14-Demethylase; Triazoles; Voriconazole
PubMed: 31514064
DOI: 10.1016/j.ejmech.2019.111660 -
Frontiers in Endocrinology 2022Green tea extract (GTE) alleviated ocular inflammations in endotoxin-induced uveitis (EIU) rat model induced by lipopolysaccharide (LPS) but the underlying mechanism is...
INTRODUCTION
Green tea extract (GTE) alleviated ocular inflammations in endotoxin-induced uveitis (EIU) rat model induced by lipopolysaccharide (LPS) but the underlying mechanism is unclear.
OBJECTIVES
To investigate the systematic and local mechanisms of the alleviation by untargeted metabolomics using liquid chromatography-tandem mass spectrometry.
METHODS
Sprague-Dawley rats were divided into control group, LPS treatment group, and LPS treatment group treated with GTE two hours after LPS injection. The eyes were monitored by slip lamp and electroretinography examination after 24 hours. The plasma and retina were collected for metabolomics analysis.
RESULTS
In LPS treated rats, the iris showed hyperemia. Plasma prostaglandins, arachidonic acids, corticosteroid metabolites, and bile acid metabolites increased. In the retina, histamine antagonists, corticosteroids, membrane phospholipids, free antioxidants, and sugars also increased but fatty acid metabolites, N-acetylglucosamine-6-sulphate, pyrocatechol, and adipic acid decreased. After GTE treatment, the a- and b- waves of electroretinography increased by 13%. Plasma phosphorylcholine lipids increased but plasma prostaglandin E1, cholanic metabolites, and glutarylglycine decreased. In the retina, tetranor-PGAM, pantothenic derivatives, 2-ethylacylcarinitine, and kynuramine levels decreased but anti-oxidative seleno-peptide level increased. Only phospholipids, fatty acids, and arachidonic acid metabolites in plasma and in the retina had significant correlation (p < 0.05, r > 0.4 or r < -0.4).
CONCLUSIONS
The results showed GTE indirectly induced systemic phosphorylcholine lipids to suppress inflammatory responses, hepatic damage, and respiratory mitochondrial stress in EIU rats induced by LPS. Phospholipids may be a therapeutic target of GTE for anterior chamber inflammation.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Endotoxins; Inflammation; Lipopolysaccharides; Phosphorylcholine; Plant Extracts; Rats; Rats, Sprague-Dawley; Retina; Tea; Uveitis
PubMed: 35909558
DOI: 10.3389/fendo.2022.899271 -
Biomacromolecules Nov 2022We report the synthesis and characterization of an amphiphilic polymer comprising a hydrophobic palmitoyl (Pal) group and a zwitterionic poly(2-methacryloyloxyethyl...
We report the synthesis and characterization of an amphiphilic polymer comprising a hydrophobic palmitoyl (Pal) group and a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) block, which is capable of forming micelles as a drug carrier system for delivering hydrophobic anticancer drugs such as doxorubicin (DOX). We hypothesize that the sharp polarity contrast between the Pal domain and the pMPC block would strengthen the micelles and improve the drug loading capacity, while the pMPC shells improve the micelle stability and cellular uptake efficiency. In this study, the Pal-pMPC polymer was characterized and compared with a Pal-poly(ethylene glycol) (Pal-PEG) polymer in terms of their micelle formation, cytotoxicity, and drug loading of DOX. The DOX-loaded Pal-pMPC micelles were further evaluated for the cellular uptake and anticancer activities in cell culture systems including the non-multidrug-resistance HeLa cell line and the multidrug-resistance AT3B-1 cell line. The results showed that the Pal-pMPC polymer had a minimal toxicity. The Pal-pMPC micelles exhibited higher drug loading capacity and enhanced cellular internalization efficiency compared to micelles formed by the Pal-PEG polymer. It was also found that DOX-loaded Pal-pMPC micelles exhibited a more efficient anticancer effect than Pal-PEG micelles in multidrug-resistance cancer cells in an environment with fetal bovine serum.
Topics: Humans; Micelles; Phosphorylcholine; Polymers; HeLa Cells; Doxorubicin; Polyethylene Glycols; Antineoplastic Agents; Drug Carriers; Drug Delivery Systems
PubMed: 36103674
DOI: 10.1021/acs.biomac.2c00838 -
ACS Chemical Biology Feb 2020Zwitterionic modifications of glycans, such as phosphorylcholine and phosphoethanolamine, are known from a range of prokaryotic and eukaryotic species and are recognized...
Zwitterionic modifications of glycans, such as phosphorylcholine and phosphoethanolamine, are known from a range of prokaryotic and eukaryotic species and are recognized by mammalian antibodies and pentraxins; however, defined saccharide ligands modified with these zwitterionic moieties for high-throughput studies are lacking. In this study, we prepared and tested example mono- and disaccharides 6-substituted with either phosphorylcholine or phosphoethanolamine as bovine serum albumin neoglycoconjugates or printed in a microarray format for subsequent assessment of their binding to lectins, pentraxins, and antibodies. C-Reactive protein and anti-phosphorylcholine antibodies bound specifically to ligands with phosphorylcholine, but recognition by concanavalin A was abolished or decreased as compared with that to the corresponding nonzwitterionic compounds. Furthermore, in array format, the phosphorylcholine-modified ligands were recognized by IgG and IgM in sera of either non-infected or nematode-infected dogs and pigs. Thereby, these new compounds are defined ligands which allow the assessment of glycan-bound phosphorylcholine as a target of both the innate and adaptive immune systems in mammals.
Topics: Animals; Ascariasis; Ascaris; C-Reactive Protein; Carbohydrate Sequence; Cattle; Dirofilaria immitis; Dirofilariasis; Dogs; Ethanolamines; Glycoconjugates; Humans; Immunoglobulin G; Immunoglobulin M; Ligands; Phosphorylcholine; Protein Binding; Serum Albumin, Bovine; Serum Amyloid P-Component; Swine
PubMed: 31935056
DOI: 10.1021/acschembio.9b00794 -
PLoS Neglected Tropical Diseases May 2021Cutaneous leishmaniasis (CL) in Ethiopia, caused by Leishmania aethiopica, is often severe and hard to treat compared to CL caused by other species elsewhere....
BACKGROUND
Cutaneous leishmaniasis (CL) in Ethiopia, caused by Leishmania aethiopica, is often severe and hard to treat compared to CL caused by other species elsewhere. Miltefosine is the only oral anti-leishmanial drug, with a favorable side-effect profile compared to routinely available sodium stibogluconate (SSG), but evidence about its use for L. aethiopica is lacking.
METHODOLOGY AND PRINCIPAL FINDINGS
In an observational cohort study, treatment outcomes, safety and adherence among CL patients who required systemic treatment and received miltefosine for 28 days in Boru Meda Hospital and University of Gondar Hospital were studied. Patient cure was defined as 100% flattening for non-ulcerated lesions and 100% flattening and 100% re-epithelization for ulcerated lesions. Outcomes were documented for day 28, 90 and 180, both per site, and pooled, adjusting for site as a fixed effect with effect coding. Among 94 included patients (32 in Gondar, 62 in Boru Meda), median lesion duration was 12 months, median size six cm, and mucosal involvement (46.8%) and diffuse (30.9%) lesions were common. Adherence to miltefosine was good, and side-effects were tolerable. Initial outcomes at day 28 were promising, with 68.8% and 94.0% of patients having good improvement or cure in Gondar and Boru Meda respectively. In Boru Meda, outcomes were good with 72.7% and 72.9% cure at day 90 and day 180 respectively. In Gondar, results were less promising, with only 12.5% and 26.7% cure at day 90 and day 180, although confidence intervals were wide. In pooled estimates, 48.7% of patients reached cure at day 180, and 32.3% relapsed. Outcomes were better in Boru Meda Hospital, for smaller lesions and for mucosal lesions.
CONCLUSIONS/SIGNIFICANCE
Based on miltefosine's good initial response, tolerable side-effects, tablet-form, we propose to include miltefosine for future clinical trials using extended treatment schedules, combination therapy, or targeting specific subgroups.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04004754.
Topics: Administration, Oral; Adolescent; Adult; Antiprotozoal Agents; Cohort Studies; Ethiopia; Female; Humans; Leishmania; Leishmaniasis, Cutaneous; Male; Phosphorylcholine; Pilot Projects; Treatment Adherence and Compliance; Treatment Outcome
PubMed: 34048461
DOI: 10.1371/journal.pntd.0009460 -
Acta Tropica Sep 2020Visceral leishmaniasis (VL) is a chronic and systemic disease; if untreated, it can cause death in a large number of cases. The therapy is based on the use of...
Visceral leishmaniasis (VL) is a chronic and systemic disease; if untreated, it can cause death in a large number of cases. The therapy is based on the use of antimonials, which have been used for over 50 years. However, cases of resistance have been reported in some countries. In this context, miltefosine (MIL) was introduced to treat antimonial unresponsive cases. Nonetheless, in recent years MIL unresponsive and relapse cases of VL have increasingly been reported. In the current study, the therapeutic potential of compound 5-(4-(3-methanesulfonatepropyl)-1H-1,2,3-triazol-1-yl)dodecyl methanesulfonate (C11), an MIL derivative, was assessed in an experimental VL hamster model. For this purpose, golden hamsters (Mesocricetus auratus) were infected with Leishmania (L.) infantum chagasi and treated daily for 10 days with C11 and MIL administered orally; in addition, Glucantime (GLU), peritoneal route, were administered at 15, 10, 50 mg/kg body weight/day, respectively. Twenty four hours after the end of treatment the animals were euthanatized; and the specimens were collected to evaluate the relative mRNA expression of cytokines IFN-γ, TNF-α, IL-17, TGF-β, IL-4 and IL-10 in fragments of the spleen and liver; moreover, the parasitism in these organs was evaluated as well as the main histopathological alterations. The C11-treated animals showed greater expression of IL-17 and TNF-α cytokines and reduced expression of IL-10 in the spleen in comparison to the infected untreated group (UTG) (p <0.05). The C11 and GLU groups showed a significant reduction in the IgG levels in comparison to the UTG group (p <0.05). Moreover, the C11-treated animals had fewer parasites in the spleen than the UTG animals (reduction of 95.9%), as well as a greater preservation of white pulp architecture in the spleen than the UTG, GLU and MIL groups (p <0.05). For the liver, the animals from the C11 and MIL groups showed a significant increase in TNF-α relative expression in comparison to the UTG animals, which would explain the increase in the number of granulomas and the reduction in the parasitic load (p <0.05). Combined, these findings indicate that C11 is an interesting compound that should be considered for the development of new drugs against VL, mainly due to its leishmanicidal effect and immunostimulating action.
Topics: Animals; Antiprotozoal Agents; Cricetinae; Cytokines; Leishmania infantum; Leishmaniasis, Visceral; Male; Meglumine Antimoniate; Mesocricetus; Phosphorylcholine; Spleen
PubMed: 32461110
DOI: 10.1016/j.actatropica.2020.105539 -
Journal of Materials Chemistry. B Jun 2020Phosphorylcholine (PC) based polymer coatings with excellent biocompatibility have shown successful commercialization in drug-eluting stents. However, poor degradability...
Phosphorylcholine (PC) based polymer coatings with excellent biocompatibility have shown successful commercialization in drug-eluting stents. However, poor degradability represents a challenge in the application of biodegradable stents. Herein, a biodegradable phosphorylcholine copolymer is developed based on one-step radical ring-opening polymerization (RROP). This copolymer was synthesized by copolymerization of a PC unit, degradable ester (2-methylene-1,3-dioxepane, MDO) unit and non-degradable butyl methacrylate (BMA) unit, which showed ratio controllability by changing the monomer ratio during polymerization. We demonstrated that the copolymer with the ratio of 34% MDO, 19% MPC and 47% BMA could form a stable coating by ultrasonic spray, and showed good blood compatibility, anti-adhesion properties, biodegradability, and rapamycin eluting capacity. In vivo study revealed its promising application as a biodegradable stent coating. This work provides a facile path to add biodegradability into PC based polymers for further bio-applications.
Topics: Animals; Cardiovascular Diseases; Cells, Cultured; Coated Materials, Biocompatible; Molecular Structure; Particle Size; Phosphorylcholine; Polymers; Rabbits; Stents; Surface Properties; Swine; Swine, Miniature
PubMed: 32458930
DOI: 10.1039/d0tb00813c -
Nanoscale Dec 2022Phosphatidylcholine (PC) lipid bilayers at surfaces massively reduce sliding friction, the hydration lubrication mechanism acting at their highly-hydrated...
Phosphatidylcholine (PC) lipid bilayers at surfaces massively reduce sliding friction, the hydration lubrication mechanism acting at their highly-hydrated phosphocholine headgroups, a central paradigm of biological lubrication, particularly at articular cartilage surfaces where low friction is crucial for joint well-being. Nanotribological measurements probed the effect on such lubrication of dehydration by dimethyl sulfoxide (DMSO), known to strongly dehydrate the phosphocholine headgroups of such PC bilayers, reduce the thickness of the inter-bilayer water layer, and thus expected to substantially degrade the hydration lubrication. Remarkably, and unexpectedly, we found that the dehydration has little effect on the friction. We used several approaches, including atomic force microscopy, small- and wide-angle X-ray scattering and all-atom molecular dynamics simulations to elucidate this. Our results show that while DMSO clearly removes hydration water from the lipid head-groups, this is offset by both higher areal head-group density and by rigidity-enhancement of the lipid bilayers, both of which act to reduce frictional dissipation. This sheds strong light on the robustness of lipid-based hydration lubrication in biological systems, despite the ubiquitous presence of bio-osmolytes which compete for hydration water.
Topics: Humans; Lubrication; Lipid Bilayers; Phosphorylcholine; Dimethyl Sulfoxide; Dehydration; Phosphatidylcholines; Water
PubMed: 36468753
DOI: 10.1039/d2nr04799c