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Journal of Pharmaceutical and... Jun 2024Corrections to the article based on comments published by Dr Acree, various models, including the modified Apelblat model, the λh model, the Jouyban-Acree model, the...
Corrigendum to "Solubility determination and thermodynamic model analysis of L-α-glyceryl phosphorylcholine in different organic solvents of 278.15 K to 323.15 K"[J. Pharm. Biomed. Anal. 241 (2024) 115998].
Corrections to the article based on comments published by Dr Acree, various models, including the modified Apelblat model, the λh model, the Jouyban-Acree model, the SUN model and the CNIBS/R-K model, recalculated, obtained new parameters and relative absolute percentage deviations.
PubMed: 38906072
DOI: 10.1016/j.jpba.2024.116269 -
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 -
The Journal of Prosthetic Dentistry Jun 2024Studies on the effect of barium silicate on the material properties of additively manufactured (AM) resins containing 2-methacryloyloxyethyl phosphorylcholine (MPC) for...
STATEMENT OF PROBLEM
Studies on the effect of barium silicate on the material properties of additively manufactured (AM) resins containing 2-methacryloyloxyethyl phosphorylcholine (MPC) for dental applications are lacking.
PURPOSE
The purpose of this in vitro study was to evaluate the mechanical properties, transmittance, and protein adsorption of MPC-containing AM resin incorporated with different barium silicate contents and to compare these findings with those of a commercially available unfilled AM resin marketed for definitive restorations.
MATERIAL AND METHODS
Resins incorporating 6 wt% MPC and 4 different concentrations of barium silicate (10 wt%, MB10; 20 wt%, MB20; 30 wt%, MB30; and 40 wt%, MB40) were prepared. An MPC-containing resin with no filler was also prepared (0 wt%, MBN). Surface roughness (n=15), Vickers hardness (n=15), flexural strength and modulus (n=15), fracture toughness (n=15), transmittance (n=15), and protein adsorption (n=3) of the filled resin specimens were measured and compared with those of commercially available unfilled resin specimens. All data were analyzed using the Kruskal-Wallis and Dunn tests (α=.05).
RESULTS
All experimental resins had higher surface roughness than the unfilled resin (P≤.048). MB40 had higher hardness, flexural strength, flexural modulus, and fracture toughness than most other groups (P≤.047). MB10 had higher transmittance than most other groups (P≤.012). All experimental resins had lower protein adsorption than the unfilled resin, regardless of the barium silicate content (P≤.023).
CONCLUSIONS
The experimental resin containing 6 wt% MPC and 40 wt% barium silicate showed better mechanical properties and lower protein adsorption than the resin with no MPC or ceramic fillers. Transmittance decreased with the increase of barium silicate in the resins.
PubMed: 38890060
DOI: 10.1016/j.prosdent.2024.05.012 -
Journal of Dentistry Jun 2024To evaluate the mechanical and biological properties of three-dimensionally (3D) printable resins filled with 2-methacryloyloxyethyl phosphorylcholine (MPC) and...
Mechanical properties, cytotoxicity, and protein adsorption of three-dimensionally printable hybrid resin containing zwitterionic polymer and silicate-based composites for dental restorations.
OBJECTIVE
To evaluate the mechanical and biological properties of three-dimensionally (3D) printable resins filled with 2-methacryloyloxyethyl phosphorylcholine (MPC) and silicate-based composites and compare with those of a commercially available 3D-printable resin for definitive restorations.
METHODS
A group of 3D-printable hybrid resins (HRs) filled with 6 wt% MPC and three different compositions of silicate-based composites (barium silicate to zirconium silicate ratios: 1.50:1 for HR1, 0.67:1 for HR2, and 0.25:1 for HR3) were prepared. The HR groups were compared with the commercially available unfilled 3D-printable resin (CR) marketed for definitive restorations in terms of flexural strength and modulus, fracture toughness, surface roughness, Vickers hardness, light transmittance (all, n=15), cytotoxicity, and protein adsorption (both, n=3). All data were analyzed by using non-parametric Kruskal-Wallis and Dunn's tests (α=.05).
RESULTS
The HR groups had significantly higher flexural strength, modulus, fracture toughness, and hardness values than the CR (P<0.001). HR3 had the highest surface roughness and light transmittance among the groups (P≤0.006). None of tested resins showed cytotoxicity. Both HR2 and HR3 showed significantly lower protein adsorption than the CR, with a difference of approximately 60% (P≤0.026).
CONCLUSION
Both HR2 and HR3 exhibited superior mechanical properties (flexural strength, flexural modulus, fracture toughness, and Vickers hardness), light transmittance, and protein-repellent activity than the CR, with no impact on cytotoxicity.
CLINICAL SIGNIFICANCE
The MPC/silicate-based composite-filled resins may be a suitable alternative for definitive restorations, given their higher mechanical properties and promising biological properties to prevent microbial adhesion and subsequent biofilm formation, as well as their non-cytotoxic properties.
PubMed: 38885733
DOI: 10.1016/j.jdent.2024.105134 -
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 -
Biomaterials Jun 2024Abdominal adhesion, a serious complication of abdominal surgery, often resists mitigation by current drug administration and physical barriers. To address this issue, we...
Abdominal adhesion, a serious complication of abdominal surgery, often resists mitigation by current drug administration and physical barriers. To address this issue, we developed an injectable, antifouling hydrogel through the free-radical polymerization of methacrylate chondroitin sulfate (CS-GMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) monomers, dubbed the CGM hydrogel. We systematically analyzed its physicochemical properties, including rheological strength, biocompatibility, and antifouling capabilities. A rat abdominal cecum adhesion model was constructed to assess the effectiveness of CGM hydrogel in preventing postoperative adhesion and recurrent adhesion. In addition, multi-omics analyses identified the relationship between adhesion development and CCL2/CCR2 interaction. Notably, CGM hydrogel can thwart the recruitment and aggregation of fibroblasts and macrophages by inhibiting the CCL2/CCR2 interaction. Moreover, CGM hydrogel significantly dampens the activity of fibrosis-linked cytokines (TGF-βR1) and recalibrates extracellular matrix deposition-related cytokines (t-PA and PAI-1, Col Ⅰ and MMP-9). Cumulatively, the dual action of CGM hydrogel-as a physical barrier and cytokine regulator-highlights its promising potential in clinical application for abdominal adhesion prevention.
PubMed: 38875883
DOI: 10.1016/j.biomaterials.2024.122661 -
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 -
Langmuir : the ACS Journal of Surfaces... Jun 2024A biocompatible and antifouling polymeric medical coating was developed through rational design for anchoring pendant groups for the modification of stainless steel....
A biocompatible and antifouling polymeric medical coating was developed through rational design for anchoring pendant groups for the modification of stainless steel. Zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) was copolymerized individually with three anchoring monomers of carboxyl acrylamides with different alkyl spacers, including acryloylglycine (2-AE), 6-acrylamidohexanoic acid (6-AH), and 11-acrylamidoundecanoic acid (11-AU). The carboxylic acid groups are responsible for the stable grafting of copolymers onto stainless steel via a coordinative interaction with metal oxides. Due to hydrophobic interaction and hydrogen bonding, the anchoring monomers enable the formation of self-assembling structures in solution and at a metallic interface, which can play an important role in the thin film formation and functionality of the coatings. Therefore, surface characterizations of anchoring monomers on stainless steel were conducted to analyze the packing density and strength of the intermolecular hydrogen bonds. The corresponding copolymers were synthesized, and their aggregate structures were assessed, showing micelle aggregation for copolymers with higher hydrophobic compositions. The synergistic effects of inter/intramolecular interactions and hydrophobicity of the anchoring monomers result in the diversity of the thickness, surface coverage, wettability, and friction of the polymeric coatings on stainless steel. More importantly, the antifouling properties of the coatings against bacteria and proteins were strongly correlated to thin film formation. Ultimately, the key lies in deciphering the molecular structure of the anchoring pendants in thin film formation and assessing the effectiveness of the coatings, which led to the development of medical coatings through the graft-onto approach.
PubMed: 38864376
DOI: 10.1021/acs.langmuir.4c01395 -
RSC Advances Jun 2024Enzymes are biological catalysts with good biocompatibility and high efficiency and have been widely used in many fields, such as wastewater treatment, biosensors, and...
Enzymes are biological catalysts with good biocompatibility and high efficiency and have been widely used in many fields, such as wastewater treatment, biosensors, and the medical industry. However, their inherently low stability under conditions of practical use limits further applications. Zwitterionic polymers possessing a pair of oppositely charged groups in their repeating units can increase protein stability because of their good biocompatibility and high water content. In this study, zwitterionic copolymer nanogels comprising poly(2-methacryloyloxyethyl phosphorylcholine (MPC)--methacrylic acid--hydroxy succinimide ester (MNHS)) (PMS) were synthesized reversible addition-fragmentation chain-transfer polymerization (RAFT). β-Galactosidase (β-gal) was post-modified within zwitterionic polymer nanogels with a covalently-bound spacer and the activity was compared with that of directly immobilized β-gal and free β-gal. Compared with direct immobilization, covalent immobilization with a spacer could reduce the structural change of β-gal, as confirmed by the circular dichroism spectra. Although the activity of β-gal decreased after immobilization, the hybrids of the β-gal immobilized nanogels, termed hybrid nanogel-enzymes, demonstrated superior stability compared to the free enzymes. The hybrid nanogel-enzymes maintained their function against inactivation by organic solvents and proteinases owing to their high water content, anti-biofouling properties, and limited mass transfer. They can also withstand protein aggregation at high temperatures and maintain their activity. Compared to direct immobilization, immobilization with a spacer resulted in a dramatic increase in the enzyme activity and a slight decrease in the stability. These results indicate that polymer nanogels containing phosphorylcholine units are promising materials for enzyme immobilization, expanding the scope of enzyme applications.
PubMed: 38863819
DOI: 10.1039/d4ra02436b -
ACS Nano Jun 2024Urinary extracellular vesicles (uEVs) are regarded as highly promising liquid-biopsy biomarkers for the early diagnosis and prognosis of bladder cancer (BC). However,...
Urinary extracellular vesicles (uEVs) are regarded as highly promising liquid-biopsy biomarkers for the early diagnosis and prognosis of bladder cancer (BC). However, detection of uEVs remains technically challenging owing to their huge heterogeneity and ultralow abundance in real samples. We herein present a choline phosphate-grafted platinum nanozyme (Pt@CP) that acts as a universal EV probe for the construction of a high-throughput and high-sensitivity immunoassay, which allowed multiplex profiling of uEV protein markers for BC detection. With the Pt@CP-based immunoassays, three uEV protein markers (MUC-1, CCDC25, and GLUT1) were identified for BC, by which the BC cases ( = 48), cystitis patients ( = 27), and healthy donors ( = 24) were discriminated with high clinical sensitivity and specificity (area under curve = 98.3%). For the BC cases ( = 9) after surgery, the Pt@CP-based immunoassay could report the postoperative residual tumor that cannot be observed by cystoscopy, which is clinically significant for assessing BC recurrence. This work provides generally high sensitivity for EV detection, facilitating the discovery and clinical use of EV-based biomarkers.
Topics: Urinary Bladder Neoplasms; Humans; Extracellular Vesicles; Biomarkers, Tumor; Phosphorylcholine; Immunoassay; Platinum; Female
PubMed: 38857428
DOI: 10.1021/acsnano.4c00280