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Advanced Materials (Deerfield Beach,... Feb 2020Hydrogels are formed using various triggers, including light irradiation, pH adjustment, heating, cooling, or chemical addition. Here, a new method for forming hydrogels...
Hydrogels are formed using various triggers, including light irradiation, pH adjustment, heating, cooling, or chemical addition. Here, a new method for forming hydrogels is introduced: ultrasound-triggered enzymatic gelation. Specifically, ultrasound is used as a stimulus to liberate liposomal calcium ions, which then trigger the enzymatic activity of transglutaminase. The activated enzyme catalyzes the formation of fibrinogen hydrogels through covalent intermolecular crosslinking. The catalysis and gelation processes are monitored in real time and both the enzyme kinetics and final hydrogel properties are controlled by varying the initial ultrasound exposure time. This technology is extended to microbubble-liposome conjugates, which exhibit a stronger response to the applied acoustic field and are also used for ultrasound-triggered enzymatic hydrogelation. To the best of the knowledge, these results are the first instance in which ultrasound is used as a trigger for either enzyme catalysis or enzymatic hydrogelation. This approach is highly versatile and can be readily applied to different ion-dependent enzymes or gelation systems. Moreover, this work paves the way for the use of ultrasound as a remote trigger for in vivo hydrogelation.
Topics: Calcium Chloride; Catalysis; Cross-Linking Reagents; Enzymes; Fibrinogen; Hydrogels; Kinetics; Liposomes; Microbubbles; Phosphatidylethanolamines; Phosphorylcholine; Polyethylene Glycols; Ultrasonic Waves
PubMed: 31922627
DOI: 10.1002/adma.201905914 -
Clinical Infectious Diseases : An... Oct 2021
Topics: Humans; Leishmaniasis, Cutaneous; Phosphorylcholine
PubMed: 33128373
DOI: 10.1093/cid/ciaa1461 -
Trends in Microbiology Jul 2023Phosphorylcholine (ChoP) can be found in all life forms. Although this molecule was first thought to be uncommon in bacteria, it is now appreciated that many bacteria... (Review)
Review
Phosphorylcholine (ChoP) can be found in all life forms. Although this molecule was first thought to be uncommon in bacteria, it is now appreciated that many bacteria express ChoP on their surface. ChoP is usually attached to a glycan structure, but in some cases, it is added as a post-translational modification to proteins. Recent findings have demonstrated the role of ChoP modification and phase variation (ON/OFF switching) in bacterial pathogenesis. However, the mechanisms of ChoP synthesis are still unclear in some bacteria. Here, we review the literature and examine the recent developments in ChoP-modified proteins and glycolipids and of ChoP biosynthetic pathways. We discuss how the well-studied Lic1 pathway exclusively mediates ChoP attachment to glycans but not to proteins. Finally, we provide a review of the role of ChoP in bacterial pathobiology and the role of ChoP in modulating the immune response.
Topics: Phosphorylcholine; Bacteria; Polysaccharides
PubMed: 36863982
DOI: 10.1016/j.tim.2023.01.006 -
Expert Review of Clinical Immunology May 2022Chronic inflammatory diseases include cardiovascular disease (CVD), atherosclerosis, rheumatic and autoimmune diseases, and others, constituting a large part of the...
INTRODUCTION
Chronic inflammatory diseases include cardiovascular disease (CVD), atherosclerosis, rheumatic and autoimmune diseases, and others, constituting a large part of the disease burden. It is therefore of major importance to improve understanding of underlying mechanisms, prediction, and treatment.
AREAS COVERED
Broad fields including atherosclerosis, immunology, and inflammation are covered, through searches on PubMed and background knowledge. Phosphorylcholine (PC) is both a danger-associated molecular pattern (DAMP), present on oxidized LDL (OxLDL) in atherosclerotic lesions and dead cells, and a pathogen associated molecular pattern (PAMP), present on microorganisms. IgM and IgG1 antibodies against PC (anti-PC) are associated with protection in several chronic inflammatory conditions, especially in CVD and atherosclerosis where most research has been done. PC-immunization ameliorates atherosclerosis in animal models and several potential underlying mechanisms have been proposed, including anti-inflammatory, decreased uptake of OxLDL in the artery wall, promotion of T regulatory cells. Anti-PC develops during the first years of life. Low levels of IgM and IgG1 anti-PC may be caused by lack of exposure to microorganisms, including nematodes and helminths among others.
EXPERT OPINION
anti-PC could improve prediction of clinical outcome and raising anti-PC could be developed into a novel therapy.
Topics: Animals; Atherosclerosis; Cardiovascular Diseases; Humans; Immunoglobulin G; Immunoglobulin M; Inflammation; Phosphorylcholine
PubMed: 35471137
DOI: 10.1080/1744666X.2022.2070475 -
Journal de Mycologie Medicale Nov 2023Fungal infections are a global health problem with high mortality and morbidity rates. Available antifungal agents have high toxicity and pharmacodynamic and... (Review)
Review
Fungal infections are a global health problem with high mortality and morbidity rates. Available antifungal agents have high toxicity and pharmacodynamic and pharmacokinetic limitations. Moreover, the increased incidence of antifungal-resistant isolates and the emergence of intrinsically resistant species raise concerns about seeking alternatives for efficient antifungal therapy. In this context, we review literature data addressing the potential action of miltefosine (MFS), an anti-Leishmania and anticancer agent, as a repositioning drug for antifungal treatment. Here, we highlight the in vitro and in vivo data, MFS possible mechanisms of action, case reports, and nanocarrier-mediated MFS delivery, focusing on fungal infection therapy. Finally, many studies have demonstrated the promising antifungal action of MFS in vitro, but there is little or no data on antifungal activity in vertebrate animal models and clinical trials, so have a need to develop more research for the repositioning of MFS as an antifungal therapy.
Topics: Animals; Antifungal Agents; Drug Repositioning; Mycoses; Phosphorylcholine
PubMed: 37774486
DOI: 10.1016/j.mycmed.2023.101436 -
International Journal of Antimicrobial... Jan 2022Miltefosine is an alkylphosphocholine agent with a broad spectrum of antiparasitic properties. For over two decades, miltefosine has remained the only oral drug licensed... (Review)
Review
Miltefosine is an alkylphosphocholine agent with a broad spectrum of antiparasitic properties. For over two decades, miltefosine has remained the only oral drug licensed and used in the treatment of the neglected tropical disease, leishmaniasis. The last extensive review of the pharmacology of miltefosine was published in 2012. Additional data on the clinical pharmacokinetics (PK) and pharmacodynamics (PD) of miltefosine have become available in the last decade, and there are ongoing and future studies in this area. Miltefosine PK are characterized by slow absorption and elimination, resulting in accumulation of drug in plasma until the end of treatment. Several recent studies established exposure-response relationships for various regimens of miltefosine in the treatment of visceral and cutaneous leishmaniasis, leading to the identification of PK parameters predictive of clinical relapse and outcome. This review provides an update on the most recent developments in the area of clinical pharmacology of miltefosine, including a discussion of the current dosing regimens.
Topics: Antiprotozoal Agents; Humans; Leishmaniasis, Cutaneous; Phosphorylcholine
PubMed: 34695563
DOI: 10.1016/j.ijantimicag.2021.106459 -
Journal of Materials Chemistry. B Sep 2020Nosocomial infections resulting from bacterial attachment on blood-contacting medical devices, as well as biofilm and thrombus formation caused by fibrin crosslinking...
Nosocomial infections resulting from bacterial attachment on blood-contacting medical devices, as well as biofilm and thrombus formation caused by fibrin crosslinking and platelet accumulation/activation are a major health concern and may lead to severe morbidity and mortality. Therefore, there is an urgent need to develop facile and efficient surface coatings with both antibiofilm and antithrombotic properties to prevent medical-device associated infections as well as thrombus formation. In this study, the copolymers containing quaternary ammonium (QA) and phosphorylcholine (PC) groups were synthesized through traditional free-radical copolymerization. The cationic group of QA provides bactericidal properties, and the cell membrane-mimicking group of PC provides antithrombotic and antifouling properties. Long-term stability of the copolymer coating was achieved via simple dip coating. X-ray photoelectron spectroscopy and water contact angle measurement demonstrated that the QA and PC groups possessed inversion properties once in contact with water allowing for long-term stability. Scanning electron microscopy and confocal laser scanning microscopy demonstrated that the copolymer coating could maintain antibiofilm properties for one week in a nutrient-rich environment. Furthermore, the copolymer coating significantly decreased platelet adhesion/activation and did not cause hemolysis. The ex vivo blood circulation showed no thrombus formation which confirmed the excellent antithrombotic property of the copolymer coating. Such coatings that maintain high cell viability and exhibit both antibiofilm and antithrombotic properties present potential applications for blood-contacting devices.
Topics: Animals; Biofilms; Coated Materials, Biocompatible; Fibrinolytic Agents; Human Umbilical Vein Endothelial Cells; Humans; Microbial Sensitivity Tests; Phosphorylcholine; Platelet Adhesiveness; Quaternary Ammonium Compounds; Rabbits; Staphylococcus aureus
PubMed: 32812621
DOI: 10.1039/d0tb01662d -
Chemical Biology & Drug Design Mar 2020Phosphatidylcholine-specific phospholipase C (PC-PLC) is one of the important members of phospholipase family which is capable of specifically hydrolyzing the third...
Phosphatidylcholine-specific phospholipase C (PC-PLC) is one of the important members of phospholipase family which is capable of specifically hydrolyzing the third phosphate linker of glycerophospholipid molecules, releasing phosphocholine and diacylglycerols (DAG). It is a crucial virulence factor of bacteria contributed to cell-to-cell spread and leading multiple diseases in mammals. Moreover, PC-PLC has a wide range of biological functions and involves in various cell signaling pathway, including apoptosis, proliferation, differentiation, and metastasis. In this study, we have synthesized 2 chiral compounds ((R)-7-amino-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ol, called R-7ABO, and (S)-7-amino-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ol, called S-7ABO) and discovered their inhibitory effect on PC-PLC activity which derived from Bacillus cereus (B. cereus) and human umbilical vein endothelial cells (HUVEC). Therefore, as two novel efficient PC-PLC inhibitors, R-7ABO and S-7ABO might become favorable tools of antibacterial therapy in B. cereus infection diseases and researching the function of PC-PLC in HUVECs.
Topics: Apoptosis; Bacillus cereus; Cell Differentiation; Cell Proliferation; Diglycerides; Enzyme Inhibitors; Glycerophospholipids; Human Umbilical Vein Endothelial Cells; Humans; Hydrolysis; Phosphorylcholine; Signal Transduction; Stereoisomerism; Structure-Activity Relationship; Type C Phospholipases
PubMed: 31442363
DOI: 10.1111/cbdd.13606 -
Journal of Neuroimmunology Dec 2019Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) which carries a significant burden of morbidity and mortality. Herein we...
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) which carries a significant burden of morbidity and mortality. Herein we examine the effects of acute treatment with tuftsin-phosphorylcholine (TPC), a novel immune-modulating helminth derived compound, on a murine model of MS. Experimental autoimmune encephalomyelitis (EAE) mice received acute treatment with TPC showed an improved clinical score and significantly less signs of inflammation and demyelination in CNS tissue compared with vehicle treated EAE mice. Our findings suggest that TPC may provide a beneficial clinical effect in EAE and may therefore have a potential value for ameliorating clinical manifestations and delaying disease progression in MS.
Topics: Animals; Drug Combinations; Encephalomyelitis, Autoimmune, Experimental; Female; Inflammation Mediators; Mice; Mice, Inbred C57BL; Phosphorylcholine; Tuftsin
PubMed: 31683117
DOI: 10.1016/j.jneuroim.2019.577070 -
Optometry and Vision Science : Official... Feb 2021Contact lens (CL) wearing may cause discomfort and eye dryness. We describe here the efficacy of a synthetic polymer in protecting both the corneal epithelial cells and... (Comparative Study)
Comparative Study
SIGNIFICANCE
Contact lens (CL) wearing may cause discomfort and eye dryness. We describe here the efficacy of a synthetic polymer in protecting both the corneal epithelial cells and the CL from desiccation damage. Artificial tears containing this polymer might be helpful to treat or prevent ocular surface damage in CL wearers.
PURPOSE
We aimed to investigate the protective effects of the synthetic polymer 2-methacryloyloxyethyl phosphorylcholine (poly-MPC) on corneal epithelial cells and CLs subjected to desiccation damage.
METHODS
The interaction of poly-MPC with the cell membrane was evaluated on human primary corneal epithelial cells (HCE-F) by the sodium dodecyl sulfate damage protection assay or the displacement of the cell-binding lectin concanavalin A (ConA). Survival in vitro of HCE-F cells and ex vivo of porcine corneas exposed to desiccating conditions after pre-treatment with poly-MPC or hyaluronic acid (HA), hypromellose (HPMC), and trehalose was evaluated by a colorimetric assay. Soft CLs were soaked overnight in a solution of poly-MPC/HPMC and then let dry in ambient air. Contact lens weight, morphology, and transparency were periodically registered until complete dryness.
RESULTS
Polymer 2-methacryloyloxyethyl phosphorylcholine and HPMC were retained on the HCE-F cell membrane more than trehalose or HA. Polymer 2-methacryloyloxyethyl phosphorylcholine, HA, and HPMC either alone or in association protected corneal cells from desiccation significantly better than did trehalose alone or in association with HA. Contact lens permeation by poly-MPC/HPMC preserved better their shape and transparency than did saline.
CONCLUSIONS
Polymer 2-methacryloyloxyethyl phosphorylcholine coats and protects corneal epithelial cells and CLs from desiccation damage more efficiently compared with trehalose and as good as other reference compounds.
Topics: Animals; Cells, Cultured; Contact Lenses, Hydrophilic; Desiccation; Dry Eye Syndromes; Epithelium, Corneal; Humans; Hyaluronic Acid; Hypromellose Derivatives; Phosphorylcholine; Polymethacrylic Acids; Prosthesis Failure; Sodium Dodecyl Sulfate; Swine; Trehalose
PubMed: 33534380
DOI: 10.1097/OPX.0000000000001642