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ACS Applied Materials & Interfaces Apr 2024The fabrication of antifouling zwitterionic polymer brushes represents a leading approach to mitigate nonspecific adhesion on the surfaces of medical devices. This...
The fabrication of antifouling zwitterionic polymer brushes represents a leading approach to mitigate nonspecific adhesion on the surfaces of medical devices. This investigation seeks to elucidate the correlation between the material composition and structural attributes of these polymer brushes in preventing protein adhesion. To achieve this goal, we modeled three different zwitterionic brushes, namely, carboxybetaine methacrylate (CBMA), sulfobetaine methacrylate (SBMA), and (2-(methacryloyloxy)ethyl)-phosphorylcholine (MPC). The simulations revealed that elevating the grafting density enhances the structural stability, hydration strength, and resistance to protein adhesion exhibited by the polymer brushes. PCBMA manifests a more robust hydration layer, while PMPC demonstrates the slightest interaction with proteins. In a comprehensive evaluation, PSBMA polymer brushes emerged as the best choice with superior stability, enhanced protein repulsion, and minimally induced protein deformation, resulting in effective resistance to nonspecific adhesion. The high-density SBMA polymer brushes significantly reduce the level of protein adhesion in AFM testing. In addition, we have pioneered the quantitative characterization of hydration repulsion in polymer brushes by analyzing the hydration repulsion characteristics at different materials and graft densities. In summary, our study provides a nuanced understanding of the material and structural determinants influencing the capacity of zwitterionic polymer brushes to thwart protein adhesion. Additionally, it presents a quantitative elucidation of hydration repulsion, contributing to the advancement and application of antifouling polymer brushes.
Topics: Polymers; Proteins; Physical Phenomena; Adsorption; Methacrylates
PubMed: 38534071
DOI: 10.1021/acsami.3c18546 -
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 -
The Journal of Physical Chemistry. B Apr 2024Zwitterionic (ZI) polymers enable the formation of noncovalent cross-links within ionic liquid electrolytes (ILEs) to create nonflammable, mechanically robust, and...
Zwitterionic (ZI) polymers enable the formation of noncovalent cross-links within ionic liquid electrolytes (ILEs) to create nonflammable, mechanically robust, and highly conductive ionogel electrolytes. In this study, ZI homopolymer poly(2-methacryloyloxyethyl phosphorylcholine) [poly(MPC)] scaffolds are synthesized in situ within lithium and/or sodium salt-based ILEs to construct a series of ionogels that contain between 3 and 15 wt % poly(MPC). Room-temperature ionic conductivity values of these ionogels are found to vary between approximately 1.3 and 2.2 mS cm. For sodium only and 1:1 lithium/sodium equimolar mixed salt ionogels containing 6 wt % poly(MPC), the ionic conductivity is found to improve by 14% compared to the neat ILE due to the presence of the ZI scaffold. Moreover, comparing the elastic modulus values of lithium- versus sodium-containing ionogels revealed a difference of up to 1 order of magnitude [10.6 vs 111 kPa, respectively, for 3 wt % poly(MPC)]. Molecular dynamics simulations of ionogel precursor solutions corroborate the experimental results by demonstrating differences in the lithium/ZI monomer and sodium/ZI monomer cluster size distributions formed, which is hypothesized to influence the scaffold network cross-link density obtained upon photopolymerization. This work provides insights into why ZI polymer-supported ionogel properties that are relevant for the development of safer electrolytes for lithium-ion and sodium-ion batteries depend upon the chemical identity of the alkali metal cation.
PubMed: 38532249
DOI: 10.1021/acs.jpcb.3c08144 -
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 -
PLoS Neglected Tropical Diseases Mar 2024Acanthamoeba keratitis (AK) is a corneal sight-threatening infection caused by the free-living amoebae of the genus Acanthamoeba. Early and appropriate treatment...
BACKGROUND
Acanthamoeba keratitis (AK) is a corneal sight-threatening infection caused by the free-living amoebae of the genus Acanthamoeba. Early and appropriate treatment significantly impacts visual outcomes. Mucoadhesive polymers such as chitosan are a potential strategy to prolong the residence time and bioavailability of the encapsulated drugs in the cornea. Regarding the recent administration of miltefosine (MF) for treating resistant AK, in the present study, we synthesized miltefosine-loaded chitosan nanoparticles (MF-CS-NPs) and evaluated them against Acanthamoeba.
METHODOLOGY/PRINCIPAL FINDINGS
Chitosan nanoparticles (CNPs) were prepared using the ionic gelation method with negatively charged tripolyphosphate (TPP). The zeta-potential (ZP) and the particle size of MF-CS-NPs were 21.8±3.2 mV and 46.61±18.16 nm, respectively. The release profile of MF-CS-NPs indicated linearity with sustained drug release. The cytotoxicity of MF-CS-NPs on the Vero cell line was 2.67 and 1.64 times lower than free MF at 24 and 48 hours. This formulation exhibited no hemolytic activity in vitro and ocular irritation in rabbit eyes. The IC50 of MF-CS-NPs showed a significant reduction by 2.06 and 1.69-fold in trophozoites at 24 and 48 hours compared to free MF. Also, the MF-CS-NPs IC50 in the cysts form was slightly decreased by 1.26 and 1.21-fold at 24 and 48 hours compared to free MF.
CONCLUSIONS
The MF-CS-NPs were more effective against the trophozoites and cysts than free MF. The nano-chitosan formulation was more effective on trophozoites than the cysts form. MF-CS-NPs reduced toxicity and improved the amoebicidal effect of MF. Nano-chitosan could be an ideal carrier that decreases the cytotoxicity of miltefosine. Further analysis in animal settings is needed to evaluate this nano-formulation for clinical ocular drug delivery.
Topics: Animals; Rabbits; Drug Carriers; Chitosan; Acanthamoeba; Nanoparticles; Phosphorylcholine
PubMed: 38527059
DOI: 10.1371/journal.pntd.0011976 -
Journal of Infection and Public Health May 2024In Europe, up to 70% of visceral leishmaniasis (VL) cases occurring in adults living with HIV. People living with HIV with VL co-infection often display persistent...
BACKGROUND
In Europe, up to 70% of visceral leishmaniasis (VL) cases occurring in adults living with HIV. People living with HIV with VL co-infection often display persistent parasitemia, requiring chronic intermittent anti-Leishmania therapies. Consequently, frequent VL relapses and higher mortality rates are common in these individuals. As such, it is of paramount importance to understand the reasons for parasite persistence to improve infection management.
METHODS
To outline possible causes for treatment failure in the context of HIV-VL, we followed a person living with HIV-VL co-infection for nine years in a 12-month period. We characterized: HIV-related clinicopathological alterations (CD4 T counts and viremia) and Leishmania-specific seroreactivity, parasitemia, quantification of pro-inflammatory cytokines upon stimulation and studied a Leishmania clinical isolate recovered during this period.
RESULTS
The subject presented controlled viremia and low CD4 counts. The subject remained PCR positive for Leishmania and also seropositive. The cellular response to parasite antigens was erratic. The isolate was identified as the first Leishmania infantum case with evidence of decreased miltefosine susceptibility in Portugal.
CONCLUSION
Treatment failure is a multifactorial process driven by host and parasite determinants. Still, the real-time determination of drug susceptibility profiles in clinical isolates is an unexplored resource in the monitoring of VL.
Topics: Adult; Humans; Portugal; Coinfection; Parasitemia; Viremia; HIV Infections; Leishmaniasis, Visceral; Leishmania infantum; Phosphorylcholine
PubMed: 38522155
DOI: 10.1016/j.jiph.2024.03.008 -
Langmuir : the ACS Journal of Surfaces... Apr 2024Formation of biofilms on equipment used in various fields, such as medicine, domestic sanitation, and marine transportation, can cause serious problems. The use of...
Formation of biofilms on equipment used in various fields, such as medicine, domestic sanitation, and marine transportation, can cause serious problems. The use of antibiofouling and bactericidal modifications is a promising strategy for inhibiting bacterial adhesion and biofilm formation. To further enhance the antibiofilm properties of a surface, various combinations of bactericidal modifications alongside antibiofouling modifications have been developed. Optimization of the arrangements of antimicrobial peptides on the antibiofouling surface would allow us to design longer-life antibiofilm surface modifications. In this study, a postmodification was conducted with different design using the antimicrobial peptide KR12 on an antibiofouling copolymer film consisting of 2-methacryloyloxyethyl phosphorylcholine, 3-methacryloxypropyl trimethoxysilane, and 3-(methacryloyloxy) propyl-tris(trimethylsilyloxy) silane. The distance of KR12 from the film was adjusted by combining different lengths of poly(ethylene glycol) (PEG) spacers (molecular weights are 2000 and 5000). The density of KR12 was ranged from 0.06 to 0.22 nm. When these modified surfaces were exposed to a nutrient-rich TSB suspension, the bacterial area formed by covered 5-127% of the original copolymer film. We found that a significant distance between the bactericidal and antibiofouling modifications, along with a higher density of bactericidal modifications, slows down the biofilm formation.
Topics: Polymers; Antimicrobial Peptides; Escherichia coli; Biofilms; Bacterial Adhesion; Anti-Bacterial Agents
PubMed: 38520398
DOI: 10.1021/acs.langmuir.4c00086 -
Acta Parasitologica Mar 2024Resistance and adverse consequences of albendazole (ABZ) in treating trichinellosis urged demand for secure and effective new drugs. The current study aimed to assess...
Appraisal of Chitosan-Coated Lipid Nano-Combination with Miltefosine and Albendazole in the Treatment of Murine Trichinellosis: Experimental Study with Evaluation of Immunological and Immunohistochemical Parameters.
PURPOSE
Resistance and adverse consequences of albendazole (ABZ) in treating trichinellosis urged demand for secure and effective new drugs. The current study aimed to assess the effect of chitosan-coated lipid nano-combination with albendazole and miltefosine (MFS) in treating experimental murine trichinellosis and evaluating pathological and immunological changes of trichinellosis.
MATERIALS AND METHODS
One hundred twenty Swiss albino mice were divided into six groups. Each group was subdivided into a and b subgroups based on the scarification time, which was 7- and 40-days post-infection (PI), respectively. The treatment efficacy was evaluated using parasitological, histopathological, serological (interleukin (IL)-12 and IL-4 serum levels), immunohistochemical (GATA3, glutathione peroxidase1 (GPX1) and caspase-3), and scanning electron microscopy (SEM) methods.
RESULTS
The most effective drug was nanostructured lipid carriers (NLCs) loaded with ABZ (G5), which showed the most significant reduction in adults and larval count (100% and 92.39%, respectively). The greatest amelioration in histopathological changes was reported in G4 treated with MFS. GATA3 and caspase-3 were significantly reduced in all treated groups. GPX1 was significantly increased in G6 treated with MFS + NLCs. The highest degenerative effects on adults and larvae by SEM were documented in G6.
CONCLUSION
Loading ABZ or MFS on chitosan-coated NLCs enhanced their efficacy against trichinellosis. Although ABZ was better than MFS, their combination should be considered as MFS caused a significant reduction in the intensity of infection. Furthermore, MFS showed anti-inflammatory (↓GATA3) and antiapoptotic effects (↓caspase-3), especially in the muscular phase. Also, when loaded with NLCS, it showed an antioxidant effect (↑GPX1).
Topics: Animals; Mice; Chitosan; Albendazole; Trichinellosis; Phosphorylcholine; Anthelmintics; Lipids; Drug Carriers; Nanoparticles; Immunohistochemistry; Male
PubMed: 38489009
DOI: 10.1007/s11686-024-00799-x -
Italian Journal of Pediatrics Mar 2024Orthostatic intolerance, which includes vasovagal syncope and postural orthostatic tachycardia syndrome, is common in children and adolescents. Elevated plasma...
BACKGROUND
Orthostatic intolerance, which includes vasovagal syncope and postural orthostatic tachycardia syndrome, is common in children and adolescents. Elevated plasma homocysteine levels might participate in the pathogenesis of orthostatic intolerance. This study was designed to analyze the plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine.
METHODS
Plasma samples from 34 orthostatic intolerance children with a plasma homocysteine concentration > 9 µmol/L and 10 healthy children were subjected to ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry analysis.
RESULTS
A total of 875 metabolites were identified, 105 of which were significantly differential metabolites. Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, histidine, isocitric acid, and DL-glutamic acid and its downstream metabolites were upregulated, whereas 1-palmitoyl-sn-glycero-3-phosphocholine, 1-stearoyl-sn-glycerol 3-phosphocholine, sphingomyelin (d18:1/18:0), betaine aldehyde, hydroxyproline, and gamma-aminobutyric acid were downregulated in the orthostatic intolerance group compared with the control group. All these metabolites were related to choline and glutamate. Heatmap analysis demonstrated a common metabolic pattern of higher choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid, and lower sphingomyelin (d18:1/18:0), 1-stearoyl-sn-glycerol 3-phosphocholine, and 1-palmitoyl-sn-glycero-3-phosphocholine in patients with certain notable metabolic changes (the special group) than in the other patients (the common group). The maximum upright heart rate, the change in heart rate from the supine to the upright position, and the rate of change in heart rate from the supine to the upright position of vasovagal syncope patients were significantly higher in the special group than in the common group (P < 0.05). Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid were positively correlated with the rate of change in heart rate from the supine to the upright position in vasovagal syncope patients (P < 0.05).
CONCLUSIONS
The levels of choline-related metabolites and glutamate-related metabolites changed significantly in orthostatic intolerance children with high levels of plasma homocysteine, and these changes were associated with the severity of illness. These results provided new light on the pathogenesis of orthostatic intolerance.
Topics: Adolescent; Child; Humans; Orthostatic Intolerance; Syncope, Vasovagal; Glutamic Acid; Glycerylphosphorylcholine; Phosphorylcholine; Sphingomyelins; Choline; Homocysteine; Glycerol
PubMed: 38486257
DOI: 10.1186/s13052-024-01601-4 -
Chinese Neurosurgical Journal Mar 2024Although flow diverter device (FDD) has brought revolutionized advances in endovascular treatment of intracranial aneurysms, it also presents considerable drawbacks as...
BACKGROUND
Although flow diverter device (FDD) has brought revolutionized advances in endovascular treatment of intracranial aneurysms, it also presents considerable drawbacks as well, as the innovation for novel device has never stopped. This preclinical research aims to evaluate the safety and efficacy of a newly developed FDD, the EMBOPIPE, through in vivo and in vitro experiments.
METHODS
Aneurysms were induced in 20 New Zealand white rabbits which were randomized to three follow-up groups according to the time elapsed after EMBOPIPE implantation (28, 90, and 180 days). Additional EMBOPIPEs were implanted in the abdominal aorta to cover the renal artery in nine rabbits. Angiography was performed immediately after device placement in all groups. Aneurysm occlusion, patency of renal arteries, and pathological outcomes were assessed. For the in vitro experiments, we measured the thrombogenic potential of EMBOPIPEs (n = 5) compared with bare stents (n = 5) using the Chandler loop model. Evaluation indicators were the platelet counts, macroscopic observations and scanning electron microscopy.
RESULTS
EMBOPIPEs were successfully deployed in 19 of 20 rabbit aneurysms (95.0%). The rates of complete or near-complete aneurysm occlusion were 73.3%, 83.3%, and 100% in the 28-, 90-, and 180-day groups, respectively. All renal arteries covered by EMBOPIPEs remained patent, and the mean difference in renal artery diameter before and after the device placement in the three groups was 0.07 mm, 0.10 mm, and 0.10 mm, respectively (p = 0.77). Renal pathology was normal in all cases. The pathological findings of the aneurysms were as follows: thickened and adequate neointimal coverage at the aneurysm neck, minimal inflammatory response, near-complete smooth muscle cell layer, and endothelialization along the device. In vitro experiments showed that the platelet counts were significantly higher in EMBOPIPE blood samples than in bare stent samples and that platelet adhesion to the device was lower in the EMBOPIPE stent struts compared with bare stent struts through macroscopic observations and scanning electron microscopy.
CONCLUSIONS
The EMBOPIPE can achieve high rates of aneurysm occlusion while maintaining excellent branch artery patency. It exhibited wonderful pathological results. This novel device with phosphorylcholine surface modification could reduce platelet thrombus attached to the stent struts.
PubMed: 38468329
DOI: 10.1186/s41016-024-00360-9