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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 -
Polymers Jun 2023A phosphorylcholine polymer (poly(MPC-co-BMA-co-TSMA), PMBT) was prepared by free radical polymerization and coated on the surface of the polymethylpentene hollow fiber...
A phosphorylcholine polymer (poly(MPC-co-BMA-co-TSMA), PMBT) was prepared by free radical polymerization and coated on the surface of the polymethylpentene hollow fiber membrane (PMP-HFM). ATR-FTIR and SEM analyses showed that the PMBT polymer containing phosphorylcholine groups was uniformly coated on the surface of the PMP-HFM. Thermogravimetric analysis showed that the PMBT had the best stability when the molar percentage of MPC monomer in the polymer was 35%. The swelling test and static contact angle test indicated that the coating had excellent hydrophilic properties. The fluorescence test results showed that the coating could resist dissolution with 90% (%) ethanol solution and 1% (%) SDS solution. The PMBT coating was shown to be able to decrease platelet adherence to the surface of the hollow fiber membrane, and lower the risk of blood clotting; it had good blood compatibility in tests of whole blood contact and platelet adhesion. These results show that the PMBT polymer may be coated on the surface of the PMP-HFM, and is helpful for improving the blood compatibility of membrane oxygenation.
PubMed: 37447527
DOI: 10.3390/polym15132881 -
ACS Omega Oct 2023Nanofibrous mats as a wound dressing have received great attention in recent year. The development of biocompatible dressings with antibiofouling capability and...
Nanofibrous mats as a wound dressing have received great attention in recent year. The development of biocompatible dressings with antibiofouling capability and long-lasting antibacterial properties is important but challenging. Antibacterial photodynamic therapy (aPDT) effectively eliminates pathogens via a photodynamic process that can circumvent the emergence of antibiotic-resistant pathogens. In this study, we integrated the zwitterionic materials (2-methacryloyloxyethyl phosphorylcholine (MPC) moiety) and aPDT photosensitizer, methylene blue (MB), to fabricate a long-lasting antibacterial nanofibrous mat using electrospinning technology. The prepared nanofibers possessed an appropriate water absorption and retention ability, superior cytocompatibility, and antibiofouling ability against both proteins and L929 cell adhesion. MB-loaded nanofibrous mats have exhibited superior aPDT against Gram-positive compared to Gram-negative under moderate irradiation (100 W m) due to the presence of an extra outer membrane of Gram-negative bacteria serving as a protective barrier. In vitro release study demonstrated that the nanofibrous mat had a long-lasting drug release profile, which can efficiently suppress bacterial growth via aPDT. The antibacterial ability of the MB-loaded nanofibrous mat was commensurate or slightly inferior to antibiotics such as tetracycline and kanamycin, suggesting that it has the potential to be used as an antibiotic alternative. Overall, this zwitterionic nanofibrous mat with long-lasting aPDT function and nonadherent properties has potential as a promising antibacterial wound dressing.
PubMed: 37841143
DOI: 10.1021/acsomega.3c03964 -
Molecular & Cellular Proteomics : MCP Dec 2023Fasciola hepatica is a global helminth parasite of humans and their livestock. The invasive stage of the parasite, the newly excysted juvenile (NEJs), relies on...
Fasciola hepatica is a global helminth parasite of humans and their livestock. The invasive stage of the parasite, the newly excysted juvenile (NEJs), relies on glycosylated excreted-secreted (ES) products and surface/somatic molecules to interact with host cells and tissues and to evade the host's immune responses, such as disarming complement and shedding bound antibody. While -omics technologies have generated extensive databases of NEJs' proteins and their expression, detailed knowledge of the glycosylation of proteins is still lacking. Here, we employed glycan, glycopeptide, and proteomic analyses to determine the glycan profile of proteins within the NEJs' somatic (Som) and ES extracts. These analyses characterized 123 NEJ glycoproteins, 71 of which are secreted proteins, and allowed us to map 356 glycopeptides and their associated 1690 N-glycan and 37 O-glycan forms to their respective proteins. We discovered abundant micro-heterogeneity in the glycosylation of individual glycosites and between different sites of multi-glycosylated proteins. The global heterogeneity across NEJs' glycoproteome was refined to 53 N-glycan and 16 O-glycan structures, ranging from highly truncated paucimannosidic structures to complex glycans carrying multiple phosphorylcholine (PC) residues, and included various unassigned structures due to unique linkages, particularly in pentosylated O-glycans. Such exclusive glycans decorate some well-known secreted molecules involved in host invasion, including cathepsin B and L peptidases, and a variety of membrane-bound glycoproteins, suggesting that they participate in host interactions. Our findings show that F. hepatica NEJs generate exceptional protein variability via glycosylation, suggesting that their molecular portfolio that communicates with the host is far more complex than previously anticipated by transcriptomic and proteomic analyses. This study opens many avenues to understand the glycan biology of F. hepatica throughout its life-stages, as well as other helminth parasites, and allows us to probe the glycosylation of individual NEJs proteins in the search for innovative diagnostics and vaccines against fascioliasis.
Topics: Animals; Humans; Fasciola hepatica; Proteomics; Secretome; Glycoproteins; Polysaccharides; Membrane Glycoproteins
PubMed: 37993102
DOI: 10.1016/j.mcpro.2023.100684 -
ACS Biomaterials Science & Engineering Aug 2023Fibrosis of implants remains a significant challenge in the use of biomedical devices and tissue engineering materials. Antifouling coatings, including synthetic...
Fibrosis of implants remains a significant challenge in the use of biomedical devices and tissue engineering materials. Antifouling coatings, including synthetic zwitterionic coatings, have been developed to prevent fouling and cell adhesion to several implantable biomaterials. While many of these coatings need covalent attachment, a conceptually simpler approach is to use a spontaneous self-assembly event to anchor the coating to a surface. This could simplify material processing through highly specific molecular recognition. Herein, we investigate the ability to utilize directional supramolecular interactions to anchor an antifouling coating to a polymer surface containing a complementary supramolecular unit. A library of controlled copolymerization of ureidopyrimidinone methacrylate (UPyMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) was prepared and their UPy composition was assessed. The MPC-UPy copolymers were characterized by H NMR, Fourier transform infrared (FTIR), and gel permeation chromatography (GPC) and found to exhibit similar mol % of UPy as compared to feed ratios and low dispersities. The copolymers were then coated on an UPy elastomer and the surfaces were assessed for hydrophilicity, protein absorption, and cell adhesion. By challenging the coatings, we found that the antifouling properties of the MPC-UPy copolymers with more UPy mol % lasted longer than the MPC homopolymer or low UPy mol % copolymers. As a result, the bioantifouling nature could be tuned to exhibit spatio-temporal control, namely, the longevity of a coating increased with UPy composition. In addition, these coatings showed nontoxicity and biocompatibility, indicating their potential use in biomaterials as antifouling coatings. Surface modification employing supramolecular interactions provided an approach that merges the simplicity and scalability of nonspecific coating methodology with the specific anchoring capacity found when using conventional covalent grafting with longevity that could be engineered by the supramolecular composition itself.
Topics: Polymers; Biofouling; Phosphorylcholine; Biocompatible Materials
PubMed: 37413691
DOI: 10.1021/acsbiomaterials.3c00425 -
Veterinary Sciences Jul 2023Anemoside B4 has a good curative effect on cows with CM; however, its impact on their metabolic profiles is unclear. Based on similar somatic cell counts and clinical...
Anemoside B4 has a good curative effect on cows with CM; however, its impact on their metabolic profiles is unclear. Based on similar somatic cell counts and clinical symptoms, nine healthy dairy cows and nine cows with CM were selected, respectively. Blood samples were collected from cows with mastitis on the day of diagnosis. Cows with mastitis were injected with anemoside B4 (0.05 mL/kg, once daily) for three consecutive days, and healthy cows were injected with the same volume of normal saline. Subsequently, blood samples were collected. The plasma metabolic profiles were analyzed using untargeted mass spectrometry, and the concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in serum were evaluated via ELISA. The cows with CM showed increased concentrations of IL-1β, IL-6, and TNF-α ( < 0.05). After treatment with anemoside B4, the concentrations of IL-1β, IL-6, and TNF-α were significantly decreased ( < 0.01). Untargeted metabolomics analysis showed that choline, glycocholic acid, PC (18:0/18:1), 20-HETE, PGF3α, and oleic acid were upregulated in cows with CM. After treatment with anemoside B4, the concentrations of PC (16:0/16:0), PC (18:0/18:1), linoleic acid, eicosapentaenoic acid, phosphorylcholine, and glycerophosphocholine were downregulated, while the LysoPC (14:0), LysoPC (18:0), LysoPC (18:1), and cis-9-palmitoleic acid were upregulated. This study indicated that anemoside B4 alleviated the inflammatory response in cows with CM mainly by regulating lipid metabolism.
PubMed: 37505842
DOI: 10.3390/vetsci10070437 -
ACS Omega Jun 2024Polymer materials are integral to diverse scientific fields, including chemical engineering and biochemical research, as well as analytical and physical chemistry. This...
Characterization of Modified PVDF Membranes Using Fourier Transform Infrared and Raman Microscopy and Infrared Nanoimaging: Challenges and Advantages of Individual Methods.
Polymer materials are integral to diverse scientific fields, including chemical engineering and biochemical research, as well as analytical and physical chemistry. This study focuses on the characterization of modified poly(vinylidene fluoride) (PVDF) membranes from both physical and chemical perspectives. Unfortunately, current surface characterization methods face various challenges when simultaneously measuring diverse material properties such as morphology and chemical composition. Addressing this issue, we introduce infrared scattering scanning near-field optical microscopy (IR-sSNOM), a modern technique with the ability to overcome limitations and provide simultaneous topographical, mechanical, and chemical information. We demonstrate the capabilities of IR-sSNOM for investigation of four samples of PVDF membranes modified with 2-(methacryloyloxyethyl)trimethylammonium iodide and/or methacryloyloxyethyl phosphorylcholine in various ratios. These membranes, desirable for their specific properties, represent a challenging material for analysis due to their thermal instability and mechanical vulnerability. Employing Fourier transform infrared (FTIR) microscopy, IR-sSNOM, and Raman microscopy, we successfully overcame these challenges by carefully selecting the experimental parameters and performing detailed characterization of the polymer samples. Valuable insights into morphological and chemical homogeneity, the abundance of modifying side chains, and the distribution of different crystal phases of PVDF were obtained. Most notably, the presence of modifying side chains was confirmed by FTIR microscopy, the Raman spectral mapping revealed the distribution of crystalline phases of the studied polymer, and the IR-sSNOM showed the abundance of chemically diverse aggregates on the surface of the membranes, thanks to the unique nanometer-scale resolution and chemical sensitivity of this technique. This comprehensive approach represents a powerful toolset for characterization of polymeric materials at the nano- and microscale. We believe that this methodology can be applied to similar samples, provided that their thermal stability is considered, opening avenues for detailed exploration of physical and chemical properties in various scientific applications.
PubMed: 38882160
DOI: 10.1021/acsomega.4c01197 -
PloS One 2024Herein we report the design and the synthesis of a library of new and more hydrophilic bisindole analogues based on our previously identified antileishmanial compound...
Herein we report the design and the synthesis of a library of new and more hydrophilic bisindole analogues based on our previously identified antileishmanial compound URB1483 that failed the preliminary in vivo test. The novel bisindoles were phenotypically screened for efficacy against Leishmania infantum promastigotes and simultaneously for toxicity on human macrophage-like THP-1 cells. Among the less toxic compounds, eight bisindoles showed IC50 below 10 μM. The most selective compound 1h (selectivity index = 10.1, comparable to miltefosine) and the most potent compound 2c (IC50 = 2.7 μM) were tested for their efficacy on L. infantum intracellular amastigotes. The compounds also demonstrated their efficacy in the in vitro infection model, showing IC50 of 11.1 and 6.8 μM for 1h and 2c, respectively. Moreover, 1h showed a better toxicity profile than the commercial drug miltefosine. For all these reasons, 1h could be a possible new starting point for hydrophilic antileishmanial agents with low cytotoxicity on human macrophage-like cells.
Topics: Leishmania infantum; Humans; Antiprotozoal Agents; THP-1 Cells; Indoles; Hydrophobic and Hydrophilic Interactions; Phosphorylcholine; Macrophages; Inhibitory Concentration 50
PubMed: 38870204
DOI: 10.1371/journal.pone.0301901 -
Molecules (Basel, Switzerland) Sep 2023The structure and dynamics of copolymers of 2-hydroxyethyl methacrylate (HEMA) with 2-methacryloyloxyethyl phosphorylcholine (MPC) were studied by molecular dynamics...
The structure and dynamics of copolymers of 2-hydroxyethyl methacrylate (HEMA) with 2-methacryloyloxyethyl phosphorylcholine (MPC) were studied by molecular dynamics simulations. In total, 20 systems were analyzed. They differed in numerical fractions of the MPC in the copolymer chain, equal to 0.26 and 0.74, in the sequence of mers, block and random, and the water content, from 0 to 60% by mass. HEMA side chains proved relatively rigid and stable in all considered configurations. MPC side chains, in contrast, were mobile and flexible. Water substantially influenced their dynamics. The copolymer swelling caused by water resulted in diffusion channels, pronounced in highly hydrated systems. Water in the hydrates existed in two states: those that bond to the polymer chain and the free one; the latter was similar to bulk water but with a lower self-diffusion coefficient. The results proved that molecular dynamics simulations could facilitate the preliminary selection of the polymer materials for specific purposes before their synthesis.
PubMed: 37764338
DOI: 10.3390/molecules28186562 -
Journal of Prosthodontic Research Jul 2023We aimed to evaluate the effectiveness of photoreactive 2-methacryloyloxyethyl phosphorylcholine (MPC) in inhibiting Candida albicans biofilm formation on polymethyl...
PURPOSE
We aimed to evaluate the effectiveness of photoreactive 2-methacryloyloxyethyl phosphorylcholine (MPC) in inhibiting Candida albicans biofilm formation on polymethyl methacrylate (PMMA) and assess its mechanism and need for re-application by evaluating its interaction with salivary mucin and durability during temperature changes.
METHODS
PMMA discs were used as specimens. The MPC coating was applied using the spray and cure technique for the treatment groups, whereas no coating was applied to the control. The MPC treatment (MT) groups were further differentiated based on the number of thermal cycles involved (0, 1000, 2500, and 5000). The optical density was measured to assess mucin adsorption (MA). Contact angle (CA) was calculated to evaluate surface hydrophilicity. The presence of MPC components on the PMMA surface was assessed using X-ray photoelectron spectroscopy (XPS). C. albicans biofilms were evaluated qualitatively (scanning electron microscope images) and quantitatively (colony-forming units (CFUs)). Statistical analysis was conducted using two-way analysis of variance and Tukey's multiple comparison test.
RESULTS
MA rate and CA increased significantly in the MT groups, which exhibited significantly fewer CFUs and thinner biofilms than those of the control group. Based on the XPS, MA, and CFU evaluations, the durability and efficacy of the MPC coating were considered stable up to 2500 thermal cycles. Additionally, a significant interaction was observed between mucin concentration and MPC efficacy.
CONCLUSIONS
The photoreactive MPC coating, which was resistant to temperature changes for approximately 3 months, effectively prevented C. albicans biofilm formation by modifying surface hydrophilicity and increasing mucin adsorption.
Topics: Candida albicans; Acrylic Resins; Polymers; Polymethyl Methacrylate; Surface Properties; Biofilms; Mucins
PubMed: 36288959
DOI: 10.2186/jpr.JPR_D_22_00102