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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 -
Toxicology and Applied Pharmacology Jul 2024Berberrubine (BRB), a main metabolite of berberine, has stronger hypoglycemic and lipid-lowering activity than its parent form. We previously found that BRB could cause...
Berberrubine (BRB), a main metabolite of berberine, has stronger hypoglycemic and lipid-lowering activity than its parent form. We previously found that BRB could cause obvious nephrotoxicity, but the molecular mechanism involved remains unknown. In this study, we systematically integrated metabolomics and quantitative proteomics to reveal the potential mechanism of nephrotoxicity caused by BRB. Metabolomic analysis revealed that 103 significant- differentially metabolites were changed. Among the mentioned compounds, significantly upregulated metabolites were observed for phosphorylcholine, sn-glycerol-3-phosphoethanolamine, and phosphatidylcholine. The top three enriched KEGG pathways were the mTOR signaling pathway, central carbon metabolism in cancer, and choline metabolism in cancer. ERK1/2 plays key roles in all three metabolic pathways. To further confirm the main signaling pathways involved, a proteomic analysis was conducted to screen for key proteins (such as Mapk1, Mapk14, and Caspase), indicating the potential involvement of cellular growth and apoptosis. Moreover, combined metabolomics and proteomics analyses revealed the participation of ERK1/2 in multiple metabolic pathways. These findings indicated that ERK1/2 regulated the significant- differentially abundant metabolites determined via metabolomics analysis. Notably, through a cellular thermal shift assay (CETSA) and molecular docking, ERK1/2 were revealed to be the direct binding target involved in BRB-induced nephrotoxicity. To summarize, this study sheds light on the understanding of severe nephrotoxicity caused by BRB and provides scientific basis for its safe use and rational development.
Topics: Berberine; Metabolomics; Proteomics; Animals; Kidney; Molecular Docking Simulation; Humans; Kidney Diseases; MAP Kinase Signaling System; Signal Transduction
PubMed: 38843998
DOI: 10.1016/j.taap.2024.116992 -
The Journal of Veterinary Medical... Jun 2024Immunoglobulin A (IgA) is notable for its broad specificity toward multiple bacteria. Phosphorylcholine (PC) plays a role in the infection of pathogenic bacteria...
Immunoglobulin A (IgA) is notable for its broad specificity toward multiple bacteria. Phosphorylcholine (PC) plays a role in the infection of pathogenic bacteria carrying PC and in the induction of IgA responses in the host immune system. The commercially available mouse monoclonal IgA, TEPC15-IgA, is a distinctive antibody with specificity for PC, warranting further exploration of its response to PC-bearing enteric bacteria. In this study, using 17 different enteric bacteria, including 3 aerobic and 14 anerobic bacteria that could be cultured in vitro, we confirmed that TEPC15-IgA recognizes 4 bacterial species: Lactobacillus taiwanensis, Limosilactobacillus frumenti, Streptococcus infantis, and Escherichia coli, although reactivity varied. Interestingly, TEPC15-IgA did not react with four of six Lactobacillus species used. Moreover, distinct target molecules associated with PC in L. taiwanensis and L. frumenti were evident, differing in molecular weight. These findings suggest that the natural generation of PC-specific IgA could prevent PC-mediated infections and potentially facilitate the formation of a microflora rich in indigenous bacteria with PC, particularly in the gastrointestinal tract.
PubMed: 38839348
DOI: 10.1292/jvms.23-0441 -
Journal of Pharmaceutical and... Sep 2024A polemic is given regarding several of the calculated curve-fit parameters that Zhou and coworkers reported in their published paper. The calculated curve-fit...
A polemic is given regarding several of the calculated curve-fit parameters that Zhou and coworkers reported in their published paper. The calculated curve-fit parameters for the Combined Nearly Ideal Binary Solvent/Redlich-Kister, Jouyban-Acree-van't Hoff, Sun and modified Apelblat models were found to give mole fraction solubilities that exceeded unity. Our analysis also found that the mean relative absolute percent deviations provided by the authors were significantly underestimated.
Topics: Solvents; Thermodynamics; Solubility; Glycerylphosphorylcholine; Models, Chemical; Temperature
PubMed: 38810329
DOI: 10.1016/j.jpba.2024.116217 -
Journal of Dentistry May 2024To create bacteria-resistant dental CAD-CAM blocks with a biofilm-resistant effect by incorporating Nano-crystalline ceramic and polymer (NCP) with...
OBJECTIVES
To create bacteria-resistant dental CAD-CAM blocks with a biofilm-resistant effect by incorporating Nano-crystalline ceramic and polymer (NCP) with 2-methacryloyloxyethyl phosphorylcholine (MPC) and sulfobetaine methacrylate (SBMA) and at an equimolar ratio, referred to as MS.
METHODS
Experimental groups comprised NCP blocks containing zwitterions at 0.15wt% (MS015) and 0.45wt% (MS045). NCP blocks without MS served as control (CTRL). Flexural strength, surface hardness, water sorption and solubility, photometric properties, and cytotoxicity were assessed for all samples. Additionally, the resistance to single and multi-species bacterial adhesion was investigated.
RESULTS
MS045 showed significant reduction in flexural strength (P < 0.01) compared to both CTRL and MS015. Both MS015 and MS045 showed significantly increased water sorption and significant reduction in water solubility compared to CTRL. Light transmission remained consistent across all MS content levels, but the irradiance value decreased by 12% in the MS045 group compared to the MS015 group. Notably, compared to the CTRL group, the MS015 group exhibited enhanced resistance to adhesion by Porphyromonas gingivalis and a multi-species salivary biofilm, with biofilm thickness and biomass reduced by 45% and 56%, respectively.
CONCLUSIONS
NCP containing 0.15% MS can effectively reduce adhesion of multiple species of bacteria while maintaining physical and mechanical properties.
CLINICAL SIGNIFICANCE
NCP integrating zwitterions is clinically advantageous in resisting bacterial adhesion at internal and external margins of milled indirect restoration.
PubMed: 38796091
DOI: 10.1016/j.jdent.2024.105054 -
Nature Communications May 2024The membrane-fusion-based internalization without lysosomal entrapment is advantageous for intracellular delivery over endocytosis. However, protein corona formed on the...
The membrane-fusion-based internalization without lysosomal entrapment is advantageous for intracellular delivery over endocytosis. However, protein corona formed on the membrane-fusogenic liposome surface converts its membrane-fusion performance to lysosome-dependent endocytosis, causing poorer delivery efficiency in biological conditions. Herein, we develop an antifouling membrane-fusogenic liposome for effective intracellular delivery in vivo. Leveraging specific lipid composition at an optimized ratio, such antifouling membrane-fusogenic liposome facilitates fusion capacity even in protein-rich conditions, attributed to the copious zwitterionic phosphorylcholine groups for protein-adsorption resistance. Consequently, the antifouling membrane-fusogenic liposome demonstrates robust membrane-fusion-mediated delivery in the medium with up to 38% fetal bovine serum, outclassing two traditional membrane-fusogenic liposomes effective at 4% and 6% concentrations. When injected into mice, antifouling membrane-fusogenic liposomes can keep their membrane-fusion-transportation behaviors, thereby achieving efficient luciferase transfection and enhancing gene-editing-mediated viral inhibition. This study provides a promising tool for effective intracellular delivery under complex physiological environments, enlightening future nanomedicine design.
Topics: Liposomes; Animals; Mice; Humans; Membrane Fusion; Endocytosis; Transfection; Gene Editing; Protein Corona; Biofouling; Female; Lipids
PubMed: 38769317
DOI: 10.1038/s41467-024-46533-z -
ACS Applied Materials & Interfaces Jun 2024This study investigated the suitability of surface modification for a long-range surface plasmon (LRSP) aptasensor using two different hydrogels, aiming at real-time...
This study investigated the suitability of surface modification for a long-range surface plasmon (LRSP) aptasensor using two different hydrogels, aiming at real-time monitoring of vancomycin (VCM) in undiluted serum and blood. Three different layer structures were formed on a gold surface of LRSP sensor chip using poly[2-methacryloyloxyethyl phosphorylcholine (MPC)---methacryloyl-(L)-tyrosinemethylester (MAT)] (PMM) and poly[MPC--2-ethylhexyl methacrylate (EHMA)--MAT] (PMEM). The peptide aptamer for VCM was immobilized in PMM and PMEM via MAT. Among four differently prepared sensor chips, the LRSP hydrogel aptasensor with PMM, referred to as the PMM hydrogel, exhibited the highest sensor output and superior antifouling properties. Following the optimization of the PMM hydrogel preparation conditions, the shelf life of the PMM hydrogel was determined to exceed 2 weeks, and the same sensor chip could be used for 102 days without significant performance deterioration. The PMM hydrogel was then applied for VCM measurement in undiluted serum in vitro, where it demonstrated a limit of detection of 0.098 μM and a dynamic range of 0.18-100 μM, covering the therapeutic range. Additionally, the PMM hydrogel enabled the continuous measurement of various VCM concentrations in serum without rinsing and showed a concentration-dependent output in undiluted blood. These findings underscore the potential of the PMM hydrogel for real-time and direct monitoring of VCM in body fluids.
Topics: Vancomycin; Humans; Hydrogels; Surface Plasmon Resonance; Biosensing Techniques; Aptamers, Peptide; Gold; Aptamers, Nucleotide; Anti-Bacterial Agents; Phosphorylcholine; Methacrylates
PubMed: 38767334
DOI: 10.1021/acsami.4c03805 -
Clinical Oral Investigations May 2024White spot lesions are the most common iatrogenic effect observed during orthodontic treatment. This study aimed to compare the surface characteristics and antibacterial... (Comparative Study)
Comparative Study
Evaluation of the surface characteristics and antibacterial properties of Titanium dioxide nanotube and methacryloyloxyethylphosphorylcholine (MPC) coated orthodontic brackets-a comparative invitro study.
OBJECTIVES
White spot lesions are the most common iatrogenic effect observed during orthodontic treatment. This study aimed to compare the surface characteristics and antibacterial action of uncoated and coated orthodontic brackets.
MATERIALS AND METHODS
Sixty commercially available stainless steel brackets were coated with TiO nanotubes and methacryloyloxyethylphosphorylcholine. The sample was divided into Group 1: uncoated orthodontic brackets, Group 2: Stainless steel brackets with TiO nanotubes coating, Group 3: Stainless steel brackets with methacryloyloxyethylphosphorylcholine coating, and Group 4: Stainless steel brackets with TiO nanotubes combined with methacryloyloxyethylphosphorylcholine coating. Surface characterization was assessed using atomic force microscopy and scanning electron microscopy. Streptococcus mutans was selected to test the antibacterial ability of the orthodontic brackets, total bacterial adhesion and bacterial viability were assessed. The brackets were subjected to scanning electron microscopy to detect the presence of biofilm.
RESULTS
The surface roughness was the greatest in Group 1 and least in Group 2 followed by Group 4 and Group 3 coated brackets. The optical density values were highest in Group 1 and lowest in Group 4. Comparison of colony counts revealed high counts in Group 1 and low counts in Group 4. A positive correlation between surface roughness and colony counts was obtained, however, was not statistically significant.
CONCLUSIONS
The coated orthodontic brackets exhibited less surface roughness than the uncoated orthodontic brackets. Group 4 coated orthodontic brackets showed the best antibacterial properties.
CLINICAL RELEVANCE
Coated orthodontic brackets prevent adhesion of streptococcus mutans and reduces plaque accumulation around the brackets thereby preventing formation of white spot lesions during orthodontic treatment.
Topics: Titanium; Orthodontic Brackets; Phosphorylcholine; Surface Properties; Streptococcus mutans; Anti-Bacterial Agents; Microscopy, Electron, Scanning; Nanotubes; Bacterial Adhesion; Microscopy, Atomic Force; Materials Testing; Stainless Steel; Methacrylates; Biofilms; Coated Materials, Biocompatible
PubMed: 38761310
DOI: 10.1007/s00784-024-05655-w -
Langmuir : the ACS Journal of Surfaces... May 2024Zwitterionic coatings provide a promising antifouling strategy against biofouling adhesion. Quaternary ammonium cationic polymers can effectively kill bacteria on the...
Zwitterionic coatings provide a promising antifouling strategy against biofouling adhesion. Quaternary ammonium cationic polymers can effectively kill bacteria on the surface, owing to their positive charges. This strategy can avoid the release of toxic biocides, which is highly desirable for constructing coatings for biomedical devices. The present work aims to develop a facile method by covalently grafting zwitterionic and cationic copolymers containing aldehydes to the remaining amine groups of self-polymerized dopamine. Reversible addition-fragmentation chain transfer polymerization was used to copolymerize either zwitterionic 2-methacryloyloxyethyl phosphorylcholine monomer (MPC) or cationic 2-(methacryloyloxy)ethyl trimethylammonium monomer (META) with 4-formyl phenyl methacrylate monomer (FPMA), and the formed copolymers poly(MPC--FPMA) and poly(META--FPMA) are denoted as MPF and MTF, respectively. MPF and MTF copolymers were then covalently grafted onto the amino groups of polydopamine-coated surfaces. PDA/MPF/MTF-coated surfaces exhibited antibacterial and antifouling properties against , , and bovine serum albumin protein. In addition, they showed excellent viability of normal human lung fibroblast cells MRC-5. We expect the facile surface modification strategy discussed here to be applicable to medical device manufacturing.
Topics: Anti-Bacterial Agents; Polymers; Staphylococcus aureus; Animals; Biofouling; Escherichia coli; Bivalvia; Surface Properties; Coated Materials, Biocompatible; Phosphorylcholine; Serum Albumin, Bovine; Humans; Methacrylates; Bacterial Adhesion; Indoles
PubMed: 38752656
DOI: 10.1021/acs.langmuir.4c00326 -
A pseudo-targeted metabolomics for discovery of potential biomarkers of cardiac hypertrophy in rats.Journal of Chromatography. B,... Jun 2024Cardiac hypertrophy (CH) is one of the stages in the occurrence and development of severe cardiovascular diseases, and exploring its biomarkers is beneficial for...
Cardiac hypertrophy (CH) is one of the stages in the occurrence and development of severe cardiovascular diseases, and exploring its biomarkers is beneficial for delaying the progression of severe cardiovascular diseases. In this research, we established a comprehensive and highly efficient pseudotargeted metabolomics method, which demonstrated a superior capacity to identify differential metabolites when compared to traditionaluntargeted metabolomics. The intra/inter-day precision and reproducibility results proved the method is reliable and precise. The established method was then applied to seek the potential differentiated metabolic biomarkers of cardiac hypertrophy (CH) rats, and oxylipins, phosphorylcholine (PC), lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE), Krebs cycle intermediates, carnitines, amino acids, and bile acids were disclosed to be the possible differentiate components. Their metabolic pathway analysis revealed that the potential metabolic alterations in CH rats were mainly associated with phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arachidonic acid metabolism, citrate cycle, glyoxylate and dicarboxylate metabolism, and tyrosine metabolism. In sum, this research provided a comprehensiveand reliable LC-MS/MS MRM platform for pseudo-targeted metabolomics investigation of disease condition, and some interesting potential biomarkers were disclosed for CH, which merit further exploration in the future.
Topics: Animals; Metabolomics; Biomarkers; Rats; Male; Rats, Sprague-Dawley; Cardiomegaly; Reproducibility of Results; Tandem Mass Spectrometry; Metabolome; Chromatography, Liquid
PubMed: 38733887
DOI: 10.1016/j.jchromb.2024.124133