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International Journal of Molecular... Jan 2024Shigellosis, an acute gastroenteritis infection caused by species, remains a public health burden in developing countries. Recently, many outbreaks due to...
Shigellosis, an acute gastroenteritis infection caused by species, remains a public health burden in developing countries. Recently, many outbreaks due to multidrug-resistant strains have been reported in high-income countries, and the lack of an effective vaccine represents a major hurdle to counteract this bacterial pathogen. Vaccine candidates against are under clinical development, including a Generalized Modules for Membrane Antigens (GMMA)-based vaccine. The mechanisms by which GMMA-based vaccines interact and activate human immune cells remain elusive. Our previous study provided the first evidence that both adaptive and innate immune cells are targeted and functionally shaped by the GMMA-based vaccine. Here, flow cytometry and confocal microscopy analysis allowed us to identify monocytes as the main target population interacting with the 1790-GMMA vaccine on human peripheral blood. In addition, transcriptomic analysis of this cell population revealed a molecular signature induced by 1790-GMMA mostly correlated with the inflammatory response and cytokine-induced processes. This also impacts the expression of genes associated with macrophages' differentiation and T cell regulation, suggesting a dual function for this vaccine platform both as an antigen carrier and as a regulator of immune cell activation and differentiation.
Topics: Humans; Monocytes; Shigella sonnei; Antigens, Bacterial; Vaccines; Blood Group Antigens; Gastroenteritis; Methylmethacrylates
PubMed: 38256189
DOI: 10.3390/ijms25021116 -
International Journal of Molecular... Mar 2024In this study, binary amorphous solid dispersions (ASDs, fisetin-Eudragit) and ternary amorphous solid inclusions (ASIs, fisetin-Eudragit-HP-β-cyclodextrin) of fisetin...
In this study, binary amorphous solid dispersions (ASDs, fisetin-Eudragit) and ternary amorphous solid inclusions (ASIs, fisetin-Eudragit-HP-β-cyclodextrin) of fisetin (FIS) were prepared by the mechanochemical method without solvent. The amorphous nature of FIS in ASDs and ASIs was confirmed using XRPD (X-ray powder diffraction). DSC (Differential scanning calorimetry) confirmed full miscibility of multicomponent delivery systems. FT-IR (Fourier-transform infrared analysis) confirmed interactions that stabilize FIS's amorphous state and identified the functional groups involved. The study culminated in evaluating the impact of amorphization on water solubility and conducting in vitro antioxidant assays: 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)-ABTS, 2,2-diphenyl-1-picrylhydrazyl-DPPH, Cupric Reducing Antioxidant Capacity-CUPRAC, and Ferric Reducing Antioxidant Power-FRAP and in vitro neuroprotective assays: inhibition of acetylcholinesterase-AChE and butyrylcholinesterase-BChE. In addition, molecular docking allowed for the determination of possible bonds and interactions between FIS and the mentioned above enzymes. The best preparation turned out to be ASI_30_EPO (ASD fisetin-Eudragit containing 30% FIS in combination with HP-β-cyclodextrin), which showed an improvement in apparent solubility (126.5 ± 0.1 µg∙mL) and antioxidant properties (ABTS: IC = 10.25 µg∙mL, DPPH: IC = 27.69 µg∙mL, CUPRAC: IC = 9.52 µg∙mL, FRAP: IC = 8.56 µg∙mL) and neuroprotective properties (inhibition AChE: 39.91%, and BChE: 42.62%).
Topics: Humans; Acetylcholinesterase; Antioxidants; Butyrylcholinesterase; Molecular Docking Simulation; Solubility; Spectroscopy, Fourier Transform Infrared; Adenoma; beta-Cyclodextrins; Polymethacrylic Acids; Sulfonic Acids; Flavonols; Benzothiazoles
PubMed: 38612460
DOI: 10.3390/ijms25073648 -
Journal of Materials Science. Materials... Jun 2024This study aimed to comprehensively assess the biocompatibility and toxicity profiles of poly(methyl methacrylate) (PMMA) and its monomeric unit, methyl methacrylate...
AIM
This study aimed to comprehensively assess the biocompatibility and toxicity profiles of poly(methyl methacrylate) (PMMA) and its monomeric unit, methyl methacrylate (MMA), crucial components in dental materials for interim prosthetic restorations.
METHODOLOGY
Molecular docking was employed to predict the binding affinities, energetics, and steric features of MMA and PMMA with selected receptors involved in bone metabolism and tissue development, including RANKL, Fibronectin, BMP9, NOTCH2, and other related receptors. The HADDOCK standalone version was utilized for docking calculations, employing a Lamarckian genetic algorithm to explore the conformational space of ligand-receptor interactions. Furthermore, molecular dynamics (MD) simulations over 100 nanoseconds were conducted using the GROMACS package to evaluate dynamic actions and structural stability. The LigandScout was utilized for pharmacophore modeling, which employs a shape-based screening approach to identify potential ligand binding sites on protein targets.
RESULTS
The molecular docking studies elucidated promising interactions between PMMA and MMA with key biomolecular targets relevant to dental applications. MD simulation results provided strong evidence supporting the structural stability of PMMA complexes over time. Pharmacophore modeling highlighted the significance of carbonyl and hydroxyl groups as pharmacophoric features, indicating compounds with favorable biocompatibility profiles.
CONCLUSION
This study underscores the potential of PMMA in dental applications, emphasizing its structural stability, molecular interactions, and safety considerations. These findings lay a foundation for future advancements in dental biomaterials, guiding the design and optimization of materials for enhanced biocompatibility. Future directions include experimental validation of computational findings and the development of PMMA-based dental materials with improved biocompatibility and clinical performance.
Topics: Molecular Docking Simulation; Biocompatible Materials; Molecular Dynamics Simulation; Polymethyl Methacrylate; Dental Materials; Materials Testing; Humans; Ligands; Computer Simulation; Binding Sites
PubMed: 38833196
DOI: 10.1007/s10856-024-06799-7 -
International Orthopaedics Nov 2023Antibiotic loaded bone cement spacers provide high local antibiotic concentrations, preserve bone stock, and reduce soft tissue contractions. The objective of this...
Enhanced antibiotic release from bone cement spacers utilizing dual antibiotic loading with elevated vancomycin concentrations in two-stage revision for periprosthetic joint infection.
PURPOSE
Antibiotic loaded bone cement spacers provide high local antibiotic concentrations, preserve bone stock, and reduce soft tissue contractions. The objective of this in-vitro study was to compare antibiotic release from spacers, aiming to discover the most optimal preparation and identify modifiable factors that can further enhance antibiotic release.
METHODS
Six distinct spacer preparation were created using three different bone cements and manual incorporation of antibiotics. During a six-week period, the release of antibiotics from each spacer was measured individually at ten predetermined time points using a chemiluminescent immunoassay.
RESULTS
Manually adding 4 g of vancomycin to every 40 g of "Palacos R + G" yielded the most favorable release profile. Throughout all preparations, antibiotic release consistently and significantly decreased over the six-week period. When incorporating a higher concentration of vancomycin, a significantly higher cumulative release of vancomycin was observed, with varying effects on the release of gentamicin. The choice of bone cement had a significant impact on antibiotic release.
CONCLUSION
To enhance antibiotic release from spacers, surgeons should manually incorporate high antibiotic concentrations into the most appropriate bone cement and keep the interim period as short as possible. Specifically, we suggest manual incorporation of 4 g of vancomycin to every 40 g of gentamicin premixed "Palacos R + G" to create bone cement spacers.
Topics: Humans; Anti-Bacterial Agents; Vancomycin; Bone Cements; Polymethyl Methacrylate; Prosthesis-Related Infections; Gentamicins; Arthritis, Infectious
PubMed: 37566227
DOI: 10.1007/s00264-023-05922-7 -
Environmental Science and Pollution... Oct 2023The powder form of the new nanofiber composite of poly(acrylonitrile-co-methylmethacrylate) (P(An-MMa)) with zirconium dioxide (ZrO) was synthesized using the sol-gel...
Study of the structural characteristics, optical properties, and electrical conductivity of doped [P(An-MMa)/ZrO] nanofiber composite using experimental data and TD-DFT/DMol computations.
The powder form of the new nanofiber composite of poly(acrylonitrile-co-methylmethacrylate) (P(An-MMa)) with zirconium dioxide (ZrO) was synthesized using the sol-gel method and subsequently converted to a thin film [P(An-MMa)/ZrO] via the physical vapor deposition (PVD) technique. Numerous characterization techniques, including Raman spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and ultraviolet-visible (UV-Vis) optical spectroscopy, were used to characterize [P(An-MMa)/ZrO]. Additionally, using density functional theory (DFT), optimization via time-dependent density functional theory (TD-DFT/DMol) and Cambridge Serial Total Energy Bundle (TD-DFT/CASTEP) was developed. The TD-DFT calculations accurately matched the observed XRD and Raman spectra and validated the molecular structure of the examined materials. The average crystallite size of [P(An-MMa)/ZrO], as determined by XRD calculations, is 171.04 nm. The SEM image depicts a one-dimensional morphological structure made up of tightly packed fibrous nanowires or brushes. The optical properties of the films were determined using optical absorbance spectrophotometric results in the 200-850-nm wavelength range. The optical energy bandgaps computed using Tauc's equation for [P(An-MMa)/ZrO] are 2.352 and 2.253 eV, respectively, whereas the isolated molecule of the composite [P(An-MMa)/ZrO] has a bandgap of 2.415 eV as determined by TD-DFT/DMol. The optical characteristics predicted by CASTEP in TD-DFT are in good agreement with the experimental values. The investigated large optical energy bandgap nanofiber composite is advantageous for some energy storage applications.
Topics: Density Functional Theory; Nanofibers; Spectrum Analysis, Raman; X-Ray Diffraction; Electric Conductivity
PubMed: 35994152
DOI: 10.1007/s11356-022-22477-z -
PloS One 2024Vertebral compression fractures are often treated with vertebroplasty, and filling the injured vertebrae with bone cement is a key part of vertebroplasty. This... (Meta-Analysis)
Meta-Analysis
A meta-analysis comparing the efficacy of mineralized collagen-polymethylmethacrylate and polymethylmethacrylate bone cements in the treatment of vertebral compression fractures.
PURPOSE
Vertebral compression fractures are often treated with vertebroplasty, and filling the injured vertebrae with bone cement is a key part of vertebroplasty. This meta-analysis was performed to compare the clinical efficacy and safety of mineralized collagen-polymethylmethacrylate (MC-PMMA) and polymethylmethacrylate (PMMA) bone cement in the treatment of vertebral compression fractures by vertebroplasty.
METHODS
A computerized search of the published literature on mineralized collagen-polymethylmethacrylate and polymethylmethacrylate bone cement in the treatment of vertebral compression fractures was conducted in the China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, Embase, and Cochrane Library. The search was carried out from the time the database was created to March 2023 and 2 researchers independently conducted literature searches to retrieve a total of 884 studies, of which 12 were included in this meta-analysis. Cochrane systematic review methods were used to assess the quality of the literature and a meta-analysis was performed using ReviewManager 5.4 software.
RESULTS
The results of the present meta-analysis showed that in postoperative adjacent vertebral fractures [OR = 0.25; 95% CI (0.15, 0.41)], postoperative cement leakage [OR = 0.45; 95% CI (0.30, 0.68)], Oswestry Disability Index (ODI) scores in the first 3 days after surgery [OR = -0.22; 95% CI (-0.42, -0.03)], ODI score at 6-12 months postoperatively [OR = -0.65; 95% CI (-0.97, -0.32)], visual analog scale (VAS) score at 6-12 months postoperatively [OR = -0.21; 95% CI (-0.46, 0.04)], and 1-year postoperative CT values [OR = 5.56; 95% CI (3.06, 8.06)], the MC-PMMA bone cement group was superior to the PMMA bone cement group. However, the differences between the two groups were not statistically different in terms of cement filling time, cement filling volume, operation time, intraoperative bleeding, hospitalization time, postoperative (<1 week, 3-6 months) vertebral body posterior convexity Cobb's angle, postoperative (<1 week, 6-12 months) vertebral body anterior margin relative height, postoperative (≤3 days, 1-3 months) pain VAS score and postoperative (1-3 months) ODI score.
CONCLUSIONS
Compared with PMMA bone cement, the application of MC-PMMA bone cement is advantageous in reducing postoperative complications (adjacent vertebral fracture rate, cement leakage rate), pain relief, and functional recovery in the long-term postoperative period (>6 months), but there is still a need for more high-quality randomized controlled studies to provide more adequate evidence.
Topics: Humans; Bone Cements; Collagen; Fractures, Compression; Kyphoplasty; Osteoporotic Fractures; Pain; Polymethyl Methacrylate; Spinal Fractures; Treatment Outcome; Vertebroplasty
PubMed: 38457423
DOI: 10.1371/journal.pone.0299325 -
Indian Journal of Ophthalmology Jul 2024The aim of this study is to describe a modified technique for internal refixation of dislocated scleral-sutured polymethylmethacrylate (PMMA) intraocular lenses (IOLs)...
The aim of this study is to describe a modified technique for internal refixation of dislocated scleral-sutured polymethylmethacrylate (PMMA) intraocular lenses (IOLs) with eyelets. Three-port pars plana vitrectomy was performed. Through the scleral fixation site, a 30-gauge needle loaded with an 8-0 polypropylene suture was inserted into the vitreous cavity. The suture end was passed through the eyelet of IOL with 25-gauge forceps. Next, it was guided out of the eye through the original scleral fixation point. The end of the exterior suture was buried with a flapless intrascleral knotting technique. Six eyes of six patients were successfully treated with this technique and followed up for 6-12 months postsurgery. In all cases, there was significant improvement in uncorrected visual acuity. IOLs were stable with proper centration and no major complications. This modified technique offers an effective and minimally invasive surgical alternative for refixation of dislocated scleral-sutured PMMA IOLs with eyelets.
Topics: Humans; Polymethyl Methacrylate; Male; Visual Acuity; Lenses, Intraocular; Female; Reoperation; Suture Techniques; Vitrectomy; Middle Aged; Sclera; Artificial Lens Implant Migration; Follow-Up Studies; Aged; Sutures; Adult
PubMed: 38905465
DOI: 10.4103/IJO.IJO_2809_23 -
Journal of the Mechanical Behavior of... Feb 2024Tissue fixation is a prevalent method for bone conservation. Bone biopsies are typically fixed in formalin, dehydrated in ethanol, and infiltrated with polymethyl...
Tissue fixation is a prevalent method for bone conservation. Bone biopsies are typically fixed in formalin, dehydrated in ethanol, and infiltrated with polymethyl methacrylate (PMMA) Since some experiments can only be performed on fixed bone samples, it is essential to understand how fixation affects the measured material properties. The aim of this study was to quantify the influence of tissue fixation on the mechanical properties of cortical ovine bone at the extracellular matrix (ECM) level with state-of-the-art micromechanical techniques. A small section from the middle of the diaphysis of two ovine tibias (3.5 and 5.5 years old) was cut in the middle and polished on each side, resulting in a pair of mirrored surfaces. For each pair, one specimen underwent a fixation protocol involving immersion in formalin, dehydration with ethanol, and infiltration with PMMA. The other specimen (mirrored) was air-dried. Six osteons were selected in both pairs, which could be identified in both specimens. The influence of fixation on the mechanical properties was first analyzed using micropillar compression tests and nanoindentation in dry condition. Additionally, changes in the degree of mineralization were evaluated with Raman spectroscopy in both fixed and native bone ECM. Finally, micro tensile experiments were conducted in the 3.5-year fixed ovine bone ECM and compared to reported properties of unfixed dry ovine bone ECM. Interestingly, we found that tissue fixation does not alter the mechanical properties of ovine cortical bone ECM compared to experiments in dry state. However, animal age increases the degree of mineralization (p = 0.0159) and compressive yield stress (p = 0.041). Tissue fixation appears therefore as a valid conservation technique for investigating the mechanical properties of dehydrated bone ECM.
Topics: Sheep; Animals; Tissue Fixation; Polymethyl Methacrylate; Formaldehyde; Ethanol; Extracellular Matrix
PubMed: 38128472
DOI: 10.1016/j.jmbbm.2023.106294 -
The Spine Journal : Official Journal of... Jul 2024Oblique lumbar interbody fusion (OLIF) can provide an ideal minimally invasive solution for achieving spinal fusion in an older, more frail population where decreased...
The effect of polymethylmethacrylate augmentation on the primary stability of stand-alone implant construct versus posterior stabilization in oblique lumbar interbody fusion with osteoporotic bone quality- a finite element study.
BACKGROUND CONTEXT
Oblique lumbar interbody fusion (OLIF) can provide an ideal minimally invasive solution for achieving spinal fusion in an older, more frail population where decreased bone quality can be a limiting factor. Stabilization can be achieved with bilateral pedicle screws (BPS), which require additional incisions and longer operative time. Alternatively, a novel self-anchoring stand-alone lateral plate system (SSA) can be used, where no additional incisions are required. Based on the relevant literature, BPS constructs provide greater primary biomechanical stability compared to lateral plate constructs, including SSA. This difference is further increased by osteoporosis. Screw augmentation in spinal fusion surgeries is commonly used; however, in the case of OLIF, it is a fairly new concept, lacking a consensus-based guideline.
PURPOSE
This comparative finite element (FE) study aimed to investigate the effect of PMMA screw augmentation on the primary stability of a stand-alone implant construct versus posterior stabilization in OLIF with osteoporotic bone quality.
STUDY DESIGN
The biomechanical effect of screw augmentation was studied inside an in-silico environment using computer-aided FE analysis.
METHODS
A previously validated and published L2-L4 FE model with normal and osteoporotic bone material properties was used. Geometries based on the OLIF implants (BPS, SSA) were created and placed inside the L3-L4 motion segment with increasing volumes (1-6 cm) of PMMA augmentation. A follower load of 400 N and 10 Nm bending moment (in the three anatomical planes) were applied to the surgical FE models with different bone material properties. The operated L3-L4 segmental range of motion (ROM), the inserted cage's maximal caudal displacements, and L4 cranial bony endplate principal stress values were measured.
RESULTS
The nonaugmented values for the BPS construct were generally lower compared to SSA, and the difference was increased by osteoporosis. In osteoporotic bone, PMMA augmentation gradually decreased the investigated parameters and the difference between the two constructs as well. Between 3 cm and 4 cm of injected PMMA volume per screw, the difference between augmented SSA and standard BPS became comparable.
CONCLUSIONS
Based on this study, augmentation can enhance the primary stability of the constructs and decrease the difference between them. Considering leakage as a possible complication, between 3 cm and 4 cm of injected PMMA per screw can be an adequate amount for SSA augmentation. However, further in silico, and possibly in vitro and clinical testing is required to thoroughly understand the investigated biomechanical aspects.
CLINICAL SIGNIFICANCE
This study sheds light on the possible biomechanical advantage offered by augmented OLIF implants and provides a theoretical augmentation amount for the SSA construct. Based on the findings, the concept of an SSA device with PMMA augmentation capability is desirable.
Topics: Spinal Fusion; Humans; Polymethyl Methacrylate; Finite Element Analysis; Lumbar Vertebrae; Osteoporosis; Pedicle Screws; Biomechanical Phenomena; Bone Cements
PubMed: 38307174
DOI: 10.1016/j.spinee.2024.01.021 -
Molecules (Basel, Switzerland) Jun 2024This study presents fibers based on methacrylic acid-methyl methacrylate (Eudragit L100) as Cu(II) adsorbents, resulting in antimicrobial complexes. Eudragit L100, an...
This study presents fibers based on methacrylic acid-methyl methacrylate (Eudragit L100) as Cu(II) adsorbents, resulting in antimicrobial complexes. Eudragit L100, an anionic copolymer synthesized by radical polymerization, was electrospun in dimethylformamide (DMF) and ethanol (EtOH). The electrospinning process was optimized through a 2-factorial design, with independent variables (copolymer concentration and EtOH/DMF volume ratio) and three repetitions at the central point. The smallest average fiber diameter (259 ± 53 nm) was obtained at 14% / Eudragit L100 and 80/20 EtOH/DMF volume ratio. The fibers were characterized using scanning electron microscopy (SEM), infrared spectroscopy in attenuated total reflectance mode (FTIR-ATR), and differential scanning calorimetry (DSC). The pseudo-second-order mechanism explained the kinetic adsorption toward Cu(II). The fibers exhibited a maximum adsorption capacity (q) of 43.70 mg/g. The DSC analysis confirmed the Cu(II) absorption, indicating complexation between metallic ions and copolymer networks. The complexed fibers showed a lower degree of swelling than the non-complexed fibers. The complexed fibers exhibited bacteriostatic activity against Gram-negative () and Gram-positive () bacteria. This study successfully optimized the electrospinning process to produce thin fibers based on Eudragit L100 for potential applications as adsorbents for Cu(II) ions in aqueous media and for controlling bacterial growth.
Topics: Copper; Polymethacrylic Acids; Anti-Infective Agents; Adsorption; Spectroscopy, Fourier Transform Infrared; Staphylococcus aureus; Methacrylates; Kinetics; Calorimetry, Differential Scanning; Microbial Sensitivity Tests
PubMed: 38930901
DOI: 10.3390/molecules29122835