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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 -
Methods in Molecular Biology (Clifton,... 2015Besides misfolded proteins, which still retain the capacity to fold into uniquely defined structures but are misled to "off-pathway" aggregation, there exists a group of... (Review)
Review
Besides misfolded proteins, which still retain the capacity to fold into uniquely defined structures but are misled to "off-pathway" aggregation, there exists a group of proteins which are unrefoldable and insoluble in buffers. Previously no general method was available to solubilize them and consequently their solution conformations could not be characterized. Recently, we discovered that these insoluble proteins could in fact be solubilized in pure water. Circular dichroism (CD) spectroscopy and nuclear magnetic resonance (NMR) characterization led to their classification into three groups, all of which lack the tight tertiary packing and consequently anticipated to unavoidably aggregate in vivo with ~150 mM ions, thus designated as "intrinsically insoluble proteins (IIPs)." It appears that eukaryotic genomes contain many "IIP," which also have a potential to interact with membranes to trigger neurodegenerative diseases. In this chapter, we provide a detailed procedure to express and purify these proteins, followed by CD and NMR spectroscopy characterization of their conformation and interaction with dodecylphosphocholine (DPC).
Topics: Animals; Circular Dichroism; Humans; Magnetic Resonance Spectroscopy; Phosphorylcholine; Protein Conformation; Protein Folding; Proteins
PubMed: 25447876
DOI: 10.1007/978-1-4939-2205-5_21 -
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 -
Cutis Oct 2020Leishmaniasis is a neglected tropical disease with notable worldwide burden and increasing prevalence in the United States due to globalization. We describe 2 cases of...
Leishmaniasis is a neglected tropical disease with notable worldwide burden and increasing prevalence in the United States due to globalization. We describe 2 cases of cutaneous leishmaniasis in New England, United States, both caused by the New World subgenus Viannia, in adults returning from Central America. Both patients underutilized preventive measures against bites from phlebotomine sand flies while abroad. They were successfully treated with oral miltefosine, which was well tolerated. Avoidance of vector transmission is the most important preventive measure. Prompt identification and treatment of cutaneous leishmaniasis caused by species with potential for mucocutaneous spread are key to limiting morbidity and mortality. This responsibility should be shared among medical specialties, including dermatologists. Partnering with the Centers for Disease Control and Prevention (CDC) is critical for timely diagnosis and thus treatment. Miltefosine should be considered a first-line agent for cutaneous leishmaniasis given its efficacy, tolerability, availability, and ease of administration. Ondansetron can be prescribed concurrently.
Topics: Adult; Antiprotozoal Agents; Female; Humans; Leishmaniasis, Cutaneous; Male; Middle Aged; Phosphorylcholine; Treatment Outcome
PubMed: 33186422
DOI: 10.12788/cutis.0086 -
Clinical Infectious Diseases : An... Oct 2021Cutaneous leishmaniasis (CL) is a neglected tropical disease causing an estimated 1 million new cases annually. While antimonial compounds are the standard of care...
BACKGROUND
Cutaneous leishmaniasis (CL) is a neglected tropical disease causing an estimated 1 million new cases annually. While antimonial compounds are the standard of care worldwide, they are associated with significant adverse effects. Miltefosine, an oral medication, is United States (US) Food and Drug Administration approved to treat CL caused by Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis. Evidence of efficacy in other species and side-effect profiles in CL has been limited.
METHODS
Twenty-six patients with CL were treated with miltefosine at the US National Institutes of Health. Species included L. braziliensis (n = 7), L. panamensis (n = 5), Leishmania mexicana (n = 1), Leishmania infantum (n = 3), Leishmania aethiopica (n = 4), Leishmania tropica (n = 2), Leishmania major (n = 1), and unspeciated (n = 3). Demographic and clinic characteristics of the participants, response to treatment, and associated adverse events were analyzed.
RESULTS
Treatment with miltefosine resulted in cure in 77 % (20/26) of cases, with cures among all species. Common adverse events included nausea/vomiting (97%) and lack of appetite (54%). Clinical management or dose reduction was required in a third of cases. Gout occurred in 3 individuals with a prior history of gout. Most laboratory abnormalities, including elevated creatinine and aminotransferases, were mild and normalized after treatment.
CONCLUSIONS
Our data suggest that miltefosine has good but imperfect efficacy to a wide variety of Leishmania species. While side effects were common and mostly mild to moderate, some resulted in discontinuation of therapy. Due to oral administration, broad efficacy, and manageable toxicities, miltefosine is a viable alternative treatment option for CL, though cost and lack of local availability may limit its widespread use.
Topics: Antiprotozoal Agents; Humans; Leishmania infantum; Leishmaniasis, Cutaneous; Phosphorylcholine
PubMed: 33124666
DOI: 10.1093/cid/ciaa1238 -
Angewandte Chemie (International Ed. in... Jun 2020Inhibition of phospholipase A2 (PLA2) has long been considered for treating various diseases associated with an elevated PLA2 activity. However, safe and effective...
Inhibition of phospholipase A2 (PLA2) has long been considered for treating various diseases associated with an elevated PLA2 activity. However, safe and effective PLA2 inhibitors remain unavailable. Herein, we report a biomimetic nanoparticle design that enables a "lure and kill" mechanism designed for PLA2 inhibition (denoted "L&K-NP"). The L&K-NPs are made of polymeric cores wrapped with modified red blood cell membrane with two inserted key components: melittin and oleyloxyethyl phosphorylcholine (OOPC). Melittin acts as a PLA2 attractant that works together with the membrane lipids to "lure" in-coming PLA2 for attack. Meanwhile, OOPC acts as inhibitor that "kills" PLA2 upon enzymatic attack. Both compounds are integrated into the L&K-NP structure, which voids toxicity associated with free molecules. In the study, L&K-NPs effectively inhibit PLA2-induced hemolysis. In mice administered with a lethal dose of venomous PLA2, L&K-NPs also inhibit hemolysis and confer a significant survival benefit. Furthermore, L&K-NPs show no obvious toxicity in mice. and the design provides a platform technology for a safe and effective anti-PLA2 approach.
Topics: Animals; Biomimetic Materials; Erythrocyte Membrane; Hemolysis; Human Umbilical Vein Endothelial Cells; Humans; Male; Melitten; Mice, Inbred ICR; Nanoparticles; Phospholipase A2 Inhibitors; Phospholipases A2; Phosphorylcholine
PubMed: 32203634
DOI: 10.1002/anie.202002782 -
ACS Chemical Neuroscience Oct 2016
Topics: Adolescent; Antiprotozoal Agents; Centers for Disease Control and Prevention, U.S.; Central Nervous System Protozoal Infections; Communications Media; Drug Industry; Health Services Accessibility; Humans; Molecular Structure; Naegleria fowleri; Phosphorylcholine; United States
PubMed: 27756136
DOI: 10.1021/acschemneuro.6b00282 -
Colloids and Surfaces. B, Biointerfaces Sep 2017Two novel zwitterionic phosphorylcholine polymers (MTP1 and MTP2) with aggregation-induced emission (AIE) feature were prepared through reversible addition fragmentation...
Two novel zwitterionic phosphorylcholine polymers (MTP1 and MTP2) with aggregation-induced emission (AIE) feature were prepared through reversible addition fragmentation chain transfer polymerization between an AIE monomer with vinyl end group and a zwitterionic phosphorylcholine monomer. The synthesized copolymers were characterized and confirmed by H NMR, FT-IR, and X-ray photoelectron spectra. By introduction of the zwitterionic phosphorylcholine component, the synthesized copolymers showed amphiphilic properties and tended to self-assemble into fluorescent polymeric nanoparticles (FPNs) in water. The dynamic light scattering results indicated the size distribution of the MTP1 FPNs was 345±22nm, and that of the MTP2 FPNs was 147±36nm. The transmission electron microscopy results demonstrated spherical nanoparticle morphology for the FPNs. The high dispersibility of the FPNs in water was proved by the UV-vis absorption study with high transmittance of the solution. Fluorescent spectra of the prepared FPNs revealed bright green fluorescence with high fluorescence quantum yield of 45% for MTP1 and 34% for MTP2. More importantly, the FPNs showed excellent particle stability with low critical micelle concentration of 0.008mgmL for MTP1 and 0.007mgmL for MTP2. The cytotoxicity evaluation confirmed high cytocompatibility of the prepared FPNs at different concentrations, and demonstrated excellent biocompatibility for cell imaging. In virtue of the high-performance MTP1 and MTP2 FPNs, including high water dispersion, good particle stability, and excellent cytocompatibility, this work would inspire more researches about high-performance biocompatible fluorescent polymers for biomedical application.
Topics: A549 Cells; Humans; Micelles; Nanoparticles; Phosphorylcholine; Polymers
PubMed: 28586729
DOI: 10.1016/j.colsurfb.2017.05.070 -
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