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Scientific Reports Feb 2024A single and rapid method to obtain an antigenic fraction of excretory-secretory antigens (ESAs) from Fasciola hepatica suitable for serodiagnosis of fascioliasis is...
A single and rapid method to obtain an antigenic fraction of excretory-secretory antigens (ESAs) from Fasciola hepatica suitable for serodiagnosis of fascioliasis is reported. The procedure consists in the negative selection of F. hepatica ESAs by hydroxyapatite (HA) chromatography (HAC; fraction HAC-NR) followed by antigen precipitation with 50% ammonium sulphate (AS) and subsequent recovery by means of a Millex-GV or equivalent filter (Fi-SOLE fraction). Tested in indirect ELISA, the Fi-SOLE antigens detected natural infections by F. hepatica with 100% sensitivity and 98.9% specificity in sheep, and 97.7% sensitivity and 97.7% specificity in cattle, as determined by ROC analysis. The SDS-PAGE and proteomic nano-UHPLC-Tims-QTOF MS/MS analysis of fractions showed that the relative abundance of L-cathepsins and fragments thereof was 57% in fraction HAC-NR and 93.8% in fraction Fi-SOLE. The second most abundant proteins in fraction HAC-NR were fatty-acid binding proteins (11.9%). In contrast, free heme, and heme:MF6p/FhHDM-1 complexes remained strongly bond to the HA particles during HAC. Interestingly, phosphorylcholine (PC)-bearing antigens, which are a frequent source of cross-reactivity, were detected with an anti-PC mAb (BH8) in ESAs and fraction HAC-NR but were almost absent in fraction Fi-SOLE.
Topics: Animals; Sheep; Cattle; Fasciola hepatica; Antigens, Helminth; Proteomics; Tandem Mass Spectrometry; Antibodies, Helminth; Fascioliasis; Enzyme-Linked Immunosorbent Assay; Heme; Hydroxyapatites; Sheep Diseases; Sensitivity and Specificity
PubMed: 38365880
DOI: 10.1038/s41598-024-54290-8 -
Proceedings of the National Academy of... Apr 2024Fine particulate matter (PM) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM...
Fine particulate matter (PM) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM components to its toxicity, especially considering regional disparities. Moreover, prevention solutions for PM-associated health effects are scarce. In the present study, we comprehensively characterized and compared the primary PM constituents and their altered metabolites from two locations: Taiyuan and Guangzhou. Analysis of year-long PM samples revealed 84 major components, encompassing organic carbon, elemental carbon, ions, metals, and organic chemicals. PM from Taiyuan exhibited higher contamination, associated health risks, dithiothreitol activity, and cytotoxicities than Guangzhou's counterpart. Applying metabolomics, BEAS-2B lung cells exposed to PM from both cities were screened for significant alterations. A correlation analysis revealed the metabolites altered by PM and the critical toxic PM components in both regions. Among the PM-down-regulated metabolites, phosphocholine emerged as a promising intervention for PM cytotoxicities. Its supplementation effectively attenuated PM-induced energy metabolism disorder and cell death via activating fatty acid oxidation and inhibiting expression. The highlighted toxic chemicals displayed combined toxicities, potentially counteracted by phosphocholine. Our study offered a promising functional metabolite to alleviate PM-induced cellular disorder and provided insights into the geo-based variability in toxic PM components.
Topics: Humans; Air Pollutants; Phosphorylcholine; Particulate Matter; Lung; Carbon; Mitochondrial Diseases; Environmental Monitoring
PubMed: 38530899
DOI: 10.1073/pnas.2317574121 -
Langmuir : the ACS Journal of Surfaces... Apr 2024The zwitterionic groups possess strong dipole moments, leading to inter- or intrachain interactions among zwitterionic polymers. This study aims to demonstrate the...
The zwitterionic groups possess strong dipole moments, leading to inter- or intrachain interactions among zwitterionic polymers. This study aims to demonstrate the interaction of polyzwitterions poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), and poly(carboxybetaine methacrylate) (PCBMA) with electrified surfaces, despite their electrically neutral nature. We studied the adsorption of polyzwitterions and their monomers on electrified surfaces by using an electrochemical quartz crystal microbalance with dissipation (EQCM-D). The interaction between zwitterionic molecules and charged surfaces is explored by adjusting the surface potentials. Interestingly, the adsorption of polyzwitterions can be influenced by external potential, primarily due to the formation of polyzwitterions restricting the mobility of zwitterionic groups, affecting the adsorption behavior of polyzwitterions based on the surface potential. The impact is determined by the arrangement of positive and negative ions within the zwitterionic groups, which are the dipole orientation. Additionally, surface potentials determine the adsorption rate, amount, and chain conformation of the adsorbed thin polyzwitterion layers. The effect of ionic strength was investigated by introducing electrolytes into the aqueous solutions to assess the range of influenced surface potentials.
PubMed: 38532553
DOI: 10.1021/acs.langmuir.4c00343 -
Nature Communications May 2024The membrane-fusion-based internalization without lysosomal entrapment is advantageous for intracellular delivery over endocytosis. However, protein corona formed on the...
The membrane-fusion-based internalization without lysosomal entrapment is advantageous for intracellular delivery over endocytosis. However, protein corona formed on the membrane-fusogenic liposome surface converts its membrane-fusion performance to lysosome-dependent endocytosis, causing poorer delivery efficiency in biological conditions. Herein, we develop an antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo. Leveraging specific lipid composition at an optimized ratio, such antifouling membrane-fusogenic liposome facilitates fusion capacity even in protein-rich conditions, attributed to the copious zwitterionic phosphorylcholine groups for protein-adsorption resistance. Consequently, the antifouling membrane-fusogenic liposome demonstrates robust membrane-fusion-mediated delivery in the medium with up to 38% fetal bovine serum, outclassing two traditional membrane-fusogenic liposomes effective at 4% and 6% concentrations. When injected into mice, antifouling membrane-fusogenic liposomes can keep their membrane-fusion-transportation behaviors, thereby achieving efficient luciferase transfection and enhancing gene-editing-mediated viral inhibition. This study provides a promising tool for effective intracellular delivery under complex physiological environments, enlightening future nanomedicine design.
Topics: Liposomes; Animals; Mice; Humans; Membrane Fusion; Endocytosis; Transfection; Gene Editing; Protein Corona; Biofouling; Female; Lipids
PubMed: 38769317
DOI: 10.1038/s41467-024-46533-z -
Nanomaterials (Basel, Switzerland) Jan 2024Sodium- (Na) and potassium- (K) ion batteries are cost-effective alternatives to lithium-ion (Li) batteries due to the abundant sodium and potassium resources. Solid...
Sodium- (Na) and potassium- (K) ion batteries are cost-effective alternatives to lithium-ion (Li) batteries due to the abundant sodium and potassium resources. Solid polymer electrolytes (SPEs) are essential for safer and more efficient Na and K batteries because they often exhibit low ionic conductivity at room temperature. While zwitterionic (ZW) materials enhance Li battery conductivity, their potential for Na and K transport in batteries remains unexplored. In this study, we investigated the effect of three ZW molecules (ChoPO4, i.e., 2-methacryloyloxyethyl phosphorylcholine, ImSO3, i.e., sulfobetaine ethylimidazole, and ImCO2, i.e., carboxybetaine ethylimidazole) on the dissociation of Na and K coordination with ethylene oxide (EO) chains in EO-based electrolytes through molecular dynamics simulations. Our results showed that ChoPO4 possessed the highest cation-EO dissociation ability, while ImSO3 exhibited the lowest. Such dissociation ability correlated with the cation-ZW molecule coordination strength: ChoPO4 and ImSO3 showed the strongest and the weakest coordination with cations. However, the cation-ZW molecule coordination could slow the cationic diffusion. The competition of these effects resulted in accelerating or decelerating cationic diffusion. Our simulated results showed that ImCO2 enhanced Na diffusion by 20%, while ChoPO4 and ImSO3 led to a 10% reduction. For K, ChoPO4 reduced its diffusion by 40%, while ImCO2 and ImSO3 caused a similar decrease of 15%. These findings suggest that the ZW structure and the cationic size play an important role in the ionic dissociation effect of ZW materials.
PubMed: 38276737
DOI: 10.3390/nano14020219 -
Parasite Immunology Feb 2024ES-62, a protein secreted by Acanthocheilonema viteae, is anti-inflammatory by virtue of covalently attached phosphorylcholine (PC) residues and thus a library of...
ES-62, a protein secreted by Acanthocheilonema viteae, is anti-inflammatory by virtue of covalently attached phosphorylcholine (PC) residues and thus a library of drug-like small molecule analogues (SMAs) based on its PC moieties has been designed for therapeutic purposes. Two members, SMAs 11a and 12b, were previously found to suppress production of pro-inflammatory cytokines by mouse bone marrow-derived macrophages (BMMs) exposed to cytosine-phosphate-guanosine oligodeoxynucleotides (CpG), agonists for Toll-like receptor 9. In order to explore the mechanism of action underlying such activities, an untargeted mass spectrometry-based metabolomics screen was undertaken. Stimulation of BMMs with CpG produced significant metabolic changes relating to glycolysis and the TCA cycle but the SMAs had little impact on this. Also, the SMAs did not promote alterations in metabolites known to be associated with macrophage M1/M2 polarization. Rather, BMMs exposed to SMAs 11a or 12b prior to CpG treatment, or even alone, revealed downregulation of metabolites of creatine, a molecule whose major role is in the transport of high energy phosphate from the mitochondria to the cytosol. These data therefore provide insight into a possible mechanism of action of molecules with significant therapeutic potential that has not previously been described for parasitic worm products.
Topics: Animals; Mice; Creatine; Macrophages; Anti-Inflammatory Agents; Helminths; Phosphates
PubMed: 38372616
DOI: 10.1111/pim.13026 -
Clinical Oral Investigations May 2024White spot lesions are the most common iatrogenic effect observed during orthodontic treatment. This study aimed to compare the surface characteristics and antibacterial... (Comparative Study)
Comparative Study
Evaluation of the surface characteristics and antibacterial properties of Titanium dioxide nanotube and methacryloyloxyethylphosphorylcholine (MPC) coated orthodontic brackets-a comparative invitro study.
OBJECTIVES
White spot lesions are the most common iatrogenic effect observed during orthodontic treatment. This study aimed to compare the surface characteristics and antibacterial action of uncoated and coated orthodontic brackets.
MATERIALS AND METHODS
Sixty commercially available stainless steel brackets were coated with TiO nanotubes and methacryloyloxyethylphosphorylcholine. The sample was divided into Group 1: uncoated orthodontic brackets, Group 2: Stainless steel brackets with TiO nanotubes coating, Group 3: Stainless steel brackets with methacryloyloxyethylphosphorylcholine coating, and Group 4: Stainless steel brackets with TiO nanotubes combined with methacryloyloxyethylphosphorylcholine coating. Surface characterization was assessed using atomic force microscopy and scanning electron microscopy. Streptococcus mutans was selected to test the antibacterial ability of the orthodontic brackets, total bacterial adhesion and bacterial viability were assessed. The brackets were subjected to scanning electron microscopy to detect the presence of biofilm.
RESULTS
The surface roughness was the greatest in Group 1 and least in Group 2 followed by Group 4 and Group 3 coated brackets. The optical density values were highest in Group 1 and lowest in Group 4. Comparison of colony counts revealed high counts in Group 1 and low counts in Group 4. A positive correlation between surface roughness and colony counts was obtained, however, was not statistically significant.
CONCLUSIONS
The coated orthodontic brackets exhibited less surface roughness than the uncoated orthodontic brackets. Group 4 coated orthodontic brackets showed the best antibacterial properties.
CLINICAL RELEVANCE
Coated orthodontic brackets prevent adhesion of streptococcus mutans and reduces plaque accumulation around the brackets thereby preventing formation of white spot lesions during orthodontic treatment.
Topics: Titanium; Orthodontic Brackets; Phosphorylcholine; Surface Properties; Streptococcus mutans; Anti-Bacterial Agents; Microscopy, Electron, Scanning; Nanotubes; Bacterial Adhesion; Microscopy, Atomic Force; Materials Testing; Stainless Steel; Methacrylates; Biofilms; Coated Materials, Biocompatible
PubMed: 38761310
DOI: 10.1007/s00784-024-05655-w -
PLoS Neglected Tropical Diseases Apr 2024With the current treatment options for visceral leishmaniasis (VL), recrudescence of the parasite is seen in a proportion of patients. Understanding parasite dynamics is...
BACKGROUND
With the current treatment options for visceral leishmaniasis (VL), recrudescence of the parasite is seen in a proportion of patients. Understanding parasite dynamics is crucial to improving treatment efficacy and predicting patient relapse in cases of VL. This study aimed to characterize the kinetics of circulating Leishmania parasites in the blood, during and after different antileishmanial therapies, and to find predictors for clinical relapse of disease.
METHODS
Data from three clinical trials, in which Eastern African VL patients received various antileishmanial regimens, were combined in this study. Leishmania kinetoplast DNA was quantified in whole blood with real-time quantitative PCR (qPCR) before, during, and up to six months after treatment. An integrated population pharmacokinetic-pharmacodynamic model was developed using non-linear mixed effects modelling.
RESULTS
Parasite proliferation was best described by an exponential growth model, with an in vivo parasite doubling time of 7.8 days (RSE 12%). Parasite killing by fexinidazole, liposomal amphotericin B, sodium stibogluconate, and miltefosine was best described by linear models directly relating drug concentrations to the parasite elimination rate. After treatment, parasite growth was assumed to be suppressed by the host immune system, described by an Emax model driven by the time after treatment. No predictors for the high variability in onset and magnitude of the immune response could be identified. Model-based individual predictions of blood parasite load on Day 28 and Day 56 after start of treatment were predictive for clinical relapse of disease.
CONCLUSION
This semi-mechanistic pharmacokinetic-pharmacodynamic model adequately captured the blood parasite dynamics during and after treatment, and revealed that high blood parasite loads on Day 28 and Day 56 after start of treatment are an early indication for VL relapse, which could be a useful biomarker to assess treatment efficacy of a treatment regimen in a clinical trial setting.
Topics: Leishmaniasis, Visceral; Humans; Antiprotozoal Agents; Adult; Female; Male; Young Adult; Adolescent; Africa, Eastern; Amphotericin B; Recurrence; DNA, Kinetoplast; Parasite Load; Middle Aged; Child; Antimony Sodium Gluconate; Child, Preschool; DNA, Protozoan; Nitroimidazoles; Phosphorylcholine
PubMed: 38640118
DOI: 10.1371/journal.pntd.0012078 -
PLoS Neglected Tropical Diseases Jun 2024In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of... (Randomized Controlled Trial)
Randomized Controlled Trial
A phase II, non-comparative randomised trial of two treatments involving liposomal amphotericin B and miltefosine for post-kala-azar dermal leishmaniasis in India and Bangladesh.
BACKGROUND
In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of miltefosine (MF), is low and ocular toxicity has been observed with this exposure period. We assessed the safety and efficacy of two shorter-course treatments: liposomal amphotericin B (LAmB) alone and combined with MF.
METHODOLOGY/PRINCIPAL FINDINGS
An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with parasitologically confirmed PKDL, 6 to ≤60 years. Patients were assigned to 20 mg/kg LAmB (total dose, in five injections over 15 days) alone or combined with allometric MF (3 weeks). The primary endpoint was definitive cure at 12 months, defined as complete resolution of papular and nodular lesions and >80% re-pigmentation of macular lesions. Definitive cure at 24 months was a secondary efficacy endpoint. 118/126 patients completed the trial. Definitive cure at 12 months was observed in 29% (18/63) patients receiving LAmB and 30% (19/63) receiving LAmB/MF (mITT), increasing to 58% and 66%, respectively, at 24 months. Most lesions had resolved/improved at 12 and 24 months for patients receiving LAmB (90%, 83%) and LAmB/MF (85%, 88%) by qualitative assessment. One death, unrelated to study drugs, was reported; no study drug-related serious adverse events were observed. The most frequent adverse drug reactions were MF-related vomiting and nausea, and LAmB-related hypokalaemia and infusion reactions. Most adverse events were mild; no ocular adverse events occurred.
CONCLUSIONS/SIGNIFICANCE
Both regimens are suitably safe and efficacious alternatives to long-course MF for PKDL in South Asia.
TRIAL REGISTRATION
CTRI/2017/04/008421.
Topics: Humans; Amphotericin B; Phosphorylcholine; Bangladesh; Male; Antiprotozoal Agents; Adult; Adolescent; Female; Middle Aged; Young Adult; Child; India; Leishmaniasis, Visceral; Treatment Outcome; Leishmaniasis, Cutaneous; Drug Therapy, Combination
PubMed: 38900786
DOI: 10.1371/journal.pntd.0012242 -
Biosensors Mar 2024Galactose monitoring in individuals allows the prevention of harsh health conditions related to hereditary metabolic diseases like galactosemia. Current methods of...
Galactose monitoring in individuals allows the prevention of harsh health conditions related to hereditary metabolic diseases like galactosemia. Current methods of galactose detection need development to obtain cheaper, more reliable, and more specific sensors. Enzyme-containing amperometric sensors based on galactose oxidase activity are a promising approach, which can be enhanced by means of their inclusion in a redox polymer coating. This strategy simultaneously allows the immobilization of the biocatalyst to the electroactive surface and hosts the electron shuttling units. An additional deposition of capping polymers prevents external interferences like ascorbic or uric acid as well as biofouling when measuring in physiological fuels. This work studies the protection effect of poly(2-methacryloyloxyethyl phosphorylcholine--glycidyl methacrylate (MPC) and polyvinylimidazole-polysulfostyrene (P(VI-SS)) when incorporated in the biosensor design for the detection of galactose in human plasma.
Topics: Biosensing Techniques; Humans; Galactose; Polymers; Galactose Oxidase; Methacrylates
PubMed: 38667160
DOI: 10.3390/bios14040167