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Scientific Reports Oct 2023The design of biomaterials able to facilitate cell adhesion is critical in the field of tissue engineering. Precise control of surface chemistry at the material/tissue...
The design of biomaterials able to facilitate cell adhesion is critical in the field of tissue engineering. Precise control of surface chemistry at the material/tissue interface plays a major role in enhancing the interactions between a biomaterial and living cells. Bio-integration is particularly important in case of various electrotherapies, since a close contact between tissue and electrode's surface facilitates treatment. A promising approach towards surface biofunctionalization involves the electrografting of diazonium salts followed by the modification of organic layer with pro-adhesive polypeptides. This study focuses on the modification of platinum electrodes with a 4-nitrobenzenediazonium layer, which is then converted to the aminobenzene moiety. The electrodes are further biofunctionalized with polypeptides (polylysine and polylysine/laminin) to enhance cell adhesion. This study also explores the differences between physical and chemical coupling of selected polypeptides to modulate pro-adhesive nature of Pt electrodes with respect to human neuroblastoma SH-SY5Y cells and U87 astrocytes. Our results demonstrate the significant enhancement in cell adhesion for biofunctionalized electrodes, with more amplified adhesion noted for covalently coupled polypeptides. The implications of this research are crucial for the development of more effective and functional biomaterials, particularly biomedical electrodes, which have the potential to advance the field of bioelectronics and improve patients' outcomes.
Topics: Humans; Polylysine; Adhesives; Neuroblastoma; Biocompatible Materials; Peptides; Cell Adhesion; Surface Properties
PubMed: 37884622
DOI: 10.1038/s41598-023-45694-z -
Quantitative Imaging in Medicine and... Oct 2023Visually evaluating liver function is a hot topic in hepatology research. There are few reliable and practical visualization methods for evaluating the liver function...
BACKGROUND
Visually evaluating liver function is a hot topic in hepatology research. There are few reliable and practical visualization methods for evaluating the liver function in experimental studies. In this study, we established a multimodal imaging approach for liver function evaluation and compared healthy mice with chronic alcoholic liver injury (cALI) model mice to explore its potential applicability in experimental research.
METHODS
In vivo fluorescence imaging (IVFI) technology was utilized to visually represent the clearance of indocyanine green from the liver of both healthy mice and mice with cALI. The reserve liver function was evaluated via IVFI using the Cy5.5-galactosylated polylysine probe, which targets the asialoglycoprotein receptor of hepatocytes. Hepatic microcirculation was assessed through laser speckle perfusion imaging of hepatic blood perfusion. The liver microstructure was then investigated by confocal laser endomicroscopy imaging. Finally, hepatic asialoglycoprotein receptor expression, histology, and the levels of serum alanine aminotransferase and aspartate aminotransferase were measured.
RESULTS
multimodal imaging results intuitively and dynamically showed that indocyanine green clearance [mean ± standard deviation (SD): 30.83±14.71, 95% confidence interval (CI): 20.3 to 41.35], the fluorescence signal intensity (mean ± SD: 1,217.92±117.63; 95% CI: 1,148.38 to 1,290.84) and fluorescence aggregation area (mean ± SD: 5,855.80±1,271.81; 95% CI: 5,051.57 to 6,653.88) of Cy5.5-galactosylated polylysine targeting the asialoglycoprotein receptor, and hepatic blood perfusion (mean ± SD: 1,494.86±299.33; 95% CI: 1,316.98 to 1,690.16) in model mice were significantly lower than those in healthy mice (all P<0.001). Compared to healthy mice, the model mice exhibited a significant decline in liver asialoglycoprotein receptor expression (mean ± SD: 219.03±16.34; 95% CI: 208.97 to 230.69; P<0.001), increased serum alanine aminotransferase (mean ± SD: 149.70±47.89 U/L; 95% CI: 81.75 to 128.89; P=0.01) and aspartate aminotransferase levels (mean ± SD: 106.30±36.13 U/L; 95% CI: 122.01 to 180.17; P=0.021), hepatocyte swelling and deformation, disappearance of the hepatic cord structure, partial necrosis, and disintegration of hepatocytes. The imaging features of fluorescence signals in liver regions, hepatic blood perfusion and microstructure were biologically related to hepatic asialoglycoprotein receptor expression, serum indices of liver function, and histopathology in model mice.
CONCLUSIONS
Utilizing multimodal imaging technology to assess liver function is a viable approach for experimental research, providing dynamic and intuitive visual evaluations in a rapid manner.
PubMed: 37869294
DOI: 10.21037/qims-23-122 -
European Journal of Pharmaceutics and... Nov 2023This study details the formation and characterisation of a novel nicotinamide adenine dinucleotide (NAD+)-associated polymeric nanoparticle system. The development of a...
This study details the formation and characterisation of a novel nicotinamide adenine dinucleotide (NAD+)-associated polymeric nanoparticle system. The development of a polyelectrolyte complex (PEC) composed of two natural polyelectrolytes, hyaluronic acid and poly(L-lysine), and an evaluation of its suitability for NAD+ ocular delivery, primarily based on its physicochemical properties and in vitro release profile under physiological ocular flow rates, were of key focus. Following optimisation of formulation method conditions such as complexation pH, mode of addition, and charge ratio, the PEC was successfully formulated under mild formulation conditions via polyelectrolyte complexation. With a size of 235.1 ± 19.0 nm, a PDI value of 0.214 ± 0.140, and a zeta potential value of - 38.0 ± 1.1 mV, the chosen PEC, loaded with 430 µg of NAD+ per mg of PEC, exhibited non-Fickian, sustained release at physiological flowrates of 10.9 ± 0.2 mg of NAD+ over 14 h. PECs containing up to 200 µM of NAD+ did not induce any significant cytotoxic effects on an immortalised human corneal epithelial cell line. Using fluorescent labeling, the NAD+-associated PECs demonstrated retention within the corneal epithelium layer of a porcine model up to 6 h post incubation under physiological conditions. A study of the physicochemical behaviour of the PECs, in terms of size, zeta potential and NAD+ complexation in response to environmental stimuli,highlighted the dynamic nature of the PEC matrix and its dependence on both pH and ionic condition. Considering the successful formation of reproducible NAD+-associated PECs with suitable characteristics for ocular drug delivery via an inexpensive formulation method, they provide a promising platform for NAD+ ocular delivery with a strong potential to improve ocular health.
Topics: Humans; Animals; Swine; Polyelectrolytes; Hyaluronic Acid; NAD; Polylysine; Drug Delivery Systems
PubMed: 37797681
DOI: 10.1016/j.ejpb.2023.10.004 -
The Journal of Allergy and Clinical... Nov 2023Skin testing is an important step in evaluation of penicillin allergic reactions. It includes testing to the following: amoxicillin, benzyl penicillin, and products...
BACKGROUND
Skin testing is an important step in evaluation of penicillin allergic reactions. It includes testing to the following: amoxicillin, benzyl penicillin, and products generated after penicillin administration, the major determinant hapten penicilloyl-polylysine (PPL) and the minor determinant mixture (MDM). Although PPL and MDM are available as a commercial kit, their supply and cost remain problematic.
OBJECTIVE
We aimed to evaluate the performance and utility of PPL and MDM in penicillin allergy testing.
METHODS
A retrospective audit over a 5-year period was undertaken for those with penicillin testing in a tertiary immunology unit.
RESULTS
In all, 214 patients were identified. Of those patients, 151 (70.6%) were female and the average age was 58 years. Unspecified penicillin was the most common index drug (n = 127 [59.3%]), followed by amoxicillin (n =3 [24.8%]) and amoxicillin-clavulanic acid (n = 21 [9.7%]). The result of skin testing was positive in 23 patients (10.7%); skin prick testing was positive in 10 patients (4.7%), and intradermal testing (IDT) was positive in 13 patients (6.1%), the majority of whom had identified amoxicillin or amoxicillin-clavulanic acid as the index drug (n = 22 [95.7%]). The result of testing to PPL and/or MDM was positive with IDT only (n=5 [23.8%]). PPL and MDM positivity coexisted with a positive reaction to amoxicillin IDT in 2 patients, 1 of whom passed an amoxicillin challenge. Additionally, 2 positive tests to PPL were present with a negative result for MDM; of these 2 positive results, 1 was positive to amoxicillin IDT. In only 1 case were the results of testing for MDM and PPL both positive, with negative results to all native β-lactams tested; the patient tolerated an amoxicillin challenge. Overall, the negative predictive value for both skin prick testing and IDT was 89.5%.
CONCLUSION
Benzyl penicillin and amoxicillin alone may be sufficient for testing in suspected individuals with penicillin allergy.
PubMed: 37781672
DOI: 10.1016/j.jacig.2023.100132 -
Food Chemistry: X Oct 2023For a long time, food spoilage posed a severe impairment on food safety and public health. Although chemical preservatives are commonly used to inhibit spoilage/...
For a long time, food spoilage posed a severe impairment on food safety and public health. Although chemical preservatives are commonly used to inhibit spoilage/ pathogenic microbial growth, the disadvantages of a single target, potential toxicity and high dose of use limit the better use of preservatives. In this research, the combination of natural preservatives: Natamycin (Nat), ε-polylysine (ε-PL), and Chitosan (CS) could achieve an excellent antimicrobial effect including bacteria and fungi, and reduce the usage of a single preservative. Compound preservatives could destroy microbial morphology and damage the integrity of the cell wall/membrane by leakage of protein and alkaline phosphatase (AKP). Besides, high-throughput sequencing revealed that compound preservatives could decrease microbial diversity and richness, especially, , , , and . Therefore, the combination of 1/8 × MIC CS, 1/4 × MIC ε-PL, and 1/2 × MIC Nat can achieve an excellent antibacterial effect, providing new ideas for food preservation.
PubMed: 37780335
DOI: 10.1016/j.fochx.2023.100872 -
BioRxiv : the Preprint Server For... Sep 2023, the malaria-causing parasite, is a leading cause of infection-induced deaths worldwide. The preferred treatment approach is artemisinin-combination therapy, which...
, the malaria-causing parasite, is a leading cause of infection-induced deaths worldwide. The preferred treatment approach is artemisinin-combination therapy, which couples fast-acting artemisinin derivatives with longer-acting drugs like lumefantrine, mefloquine, and amodiaquine. However, the urgency for new treatments has risen due to the parasite's growing resistance to existing therapies. Our study shows that a common characteristic of the proteome - stretches of poly-lysine residues such as those found in proteins related to adhesion and pathogenicity - can serve as an effective peptide treatment for infected erythrocytes. A single dose of these poly-basic peptides can successfully diminish parasitemia in human erythrocytes with minimal toxicity. The effectiveness of the treatment correlates with the length of the poly-lysine peptide, with 30 lysine peptides supporting the eradication of erythrocytic parasites within 72 hours. PEG-ylation of the poly-lysine peptides or utilizing poly-lysine dendrimers and polymers further increases parasite clearance efficiency and bolsters the stability of these potential new therapeutics. Lastly, our affinity pull-downs and mass-spectrometry identify outer membrane proteins as likely targets for polybasic peptide medications. Since poly-lysine dendrimers are already FDA-approved for drug delivery, their adaptation as antimalarial drugs presents a promising new therapeutic strategy.
PubMed: 37745508
DOI: 10.1101/2023.09.16.558069 -
Advanced Science (Weinheim,... Nov 2023Modulating the inflammatory microenvironment can inhibit the process of inflammatory diseases (IDs). A tri-cross-linked inflammatory microenvironment-responsive hydrogel...
Triple Cross-linked Dynamic Responsive Hydrogel Loaded with Selenium Nanoparticles for Modulating the Inflammatory Microenvironment via PI3K/Akt/NF-κB and MAPK Signaling Pathways.
Modulating the inflammatory microenvironment can inhibit the process of inflammatory diseases (IDs). A tri-cross-linked inflammatory microenvironment-responsive hydrogel with ideal mechanical properties achieves triggerable and sustained drug delivery and regulates the inflammatory microenvironment. Here, this study develops an inflammatory microenvironment-responsive hydrogel (OD-PP@SeNPs) composed of phenylboronic acid grafted polylysine (PP), oxidized dextran (OD), and selenium nanoparticles (SeNPs). The introduction of SeNPs as initiators and nano-fillers into the hydrogel results in extra cross-linking of the polymer network through hydrogen bonding. Based on Schiff base bonds, Phenylboronate ester bonds, and hydrogen bonds, a reactive oxygen species (ROS)/pH dual responsive hydrogel with a triple-network is achieved. The hydrogel has injectable, self-healing, adhesion, outstanding flexibility, suitable swelling capacity, optimal biodegradability, excellent stimuli-responsive active substance release performance, and prominent biocompatibility. Most importantly, the hydrogel with ROS scavenging and pH-regulating ability protects cells from oxidative stress and induces macrophages into M2 polarization to reduce inflammatory cytokines through PI3K/AKT/NF-κB and MAPK pathways, exerting anti-inflammatory effects and reshaping the inflammatory microenvironment, thereby effectively treating typical IDs, including S. aureus infected wound and rheumatoid arthritis in rats. In conclusion, this dynamically responsive injectable hydrogel with a triple-network structure provides an effective strategy to treat IDs, holding great promise in clinical application.
Topics: Animals; Rats; NF-kappa B; Selenium; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Hydrogels; Reactive Oxygen Species; Staphylococcus aureus; MAP Kinase Signaling System; Nanoparticles
PubMed: 37740428
DOI: 10.1002/advs.202303167 -
Biomaterials Research Sep 2023Drug-resistant bacterial infections in chronic wounds are a persistent issue, as they are resistant to antibiotics and can cause excessive inflammation due to generation...
BACKGROUND
Drug-resistant bacterial infections in chronic wounds are a persistent issue, as they are resistant to antibiotics and can cause excessive inflammation due to generation of reactive oxygen species (ROS). An effective solution would be to not only combat bacterial infections but also scavenge ROS to relieve inflammation at the wound site. Scaffolds with antioxidant properties are attractive for their ability to scavenge ROS, and there is medical demand in developing antioxidant enzyme-mimicking nanomaterials for wound healing.
METHODS
In this study, we fabricated copper-coordination polymer nanoparticles (Cu-CPNs) through a self-assembly process. Furthermore, ε-polylysine (EPL), an antibacterial and cationic polymer, was integrated into the Cu-CPNs structure through a simple one-pot self-assembly process without sacrificing the glutathione peroxidase (GPx) and superoxide dismutase (SOD)-mimicking activity of Cu-CPNs.
RESULTS
The resulting Cu-CPNs exhibit excellent antioxidant propertiesin mimicking the activity of glutathione peroxidase and superoxide dismutase and allowing them to effectively scavenge harmful ROS produced in wound sites. The in vitro experiments showed that the resulting Cu-CPNs@EPL complex have superior antioxidant properties and antibacterial effects. Bacterial metabolic analysis revealed that the complex mainly affects the cell membrane integrity and nucleic acid synthesis that leads to bacterial death.
CONCLUSIONS
The Cu-CPNs@EPL complex has impressive antioxidant properties and antibacterial effects, making it a promising solution for treating drug-resistant bacterial infections in chronic wounds. The complex's ability to neutralize multiple ROS and reduce ROS-induced inflammation can help relieve inflammation at the wound site. Schematic illustration of the ROS scavenging and bacteriostatic function induced by Cu-CPNs@EPL nanozyme in the treatment of MRSA-infected wounds.
PubMed: 37723499
DOI: 10.1186/s40824-023-00429-z -
Food Science & Nutrition Sep 2023The objective of this study was to provide formulation of a new multilayer antibacterial film and to investigate the optimal use concentration of chitosan and...
Preparation of a multilayer antibacterial film and its application for controlling postharvest disease in temperate fruit (including apple, pear, and peach) under ambient storage.
The objective of this study was to provide formulation of a new multilayer antibacterial film and to investigate the optimal use concentration of chitosan and carboxymethyl cellulose in the range from 0.5% to 2%, as well as its application for controlling postharvest disease in temperate fruit (apple, pear, and peach). The multilayer antibacterial film used chitosan (CS) and carboxymethyl cellulose (CMC) as polysaccharide macromolecule, lemon essential oil (LEO) as active agent, and ε-polylysine (ε-PL) as the main antibacterial ingredient. The results showed that the physical properties of the self-assembled film were adjusted by the electrostatic layer-by-layer (LbL) deposition. Fourier transform infrared (FT-IR) analysis and thermogravimetric (TGA) revealed that hydrogen bonds were generated during the self-assembly of CS-LEO/CMC-ε-PL film, resulting in changes in intermolecular interactions and thermal stability. Furthermore, compared with CS-LEO single-layer film, the multilayer film exhibited higher retention rate of LEO. In vivo test, the self-assembled film significantly inhibited the infection of postharvest pathogenic fungi including () and () on fruit. To summarize, the CS-LEO/CMC-ε-PL LbL self-assembly coating notably controlled postharvest pathogen rot on fruit, and reduced the loss of fruit during storage and transportation. Our results suggest that the polysaccharide-based edible coating prepared in this work may offer an alternative to synthetic waxes.
PubMed: 37701234
DOI: 10.1002/fsn3.3477 -
ACS Macro Letters Oct 2023The conjugation of a fluorophore and a variety of cell-penetrating peptides onto a RAFT agent allowed for the synthesis of polymers of defined sizes with quantifiable...
The conjugation of a fluorophore and a variety of cell-penetrating peptides onto a RAFT agent allowed for the synthesis of polymers of defined sizes with quantifiable cell-uptake. Each peptide-RAFT agent was used to polymerize acrylamide, acrylate, and styrene monomers to form high or low molecular weight polymers (here 50 or 7.5 kDa) with the peptide having no influence on the RAFT agent's control. The incorporation of a single fluorophore per polymer chain allowed cellular analysis of the uptake of the size-specific peptide-polymers via flow cytometry and confocal microscopy. The cell-penetrating peptides had a direct effect on the efficiency of polymer uptake for both high and low molecular weight polymers, demonstrating the versatility of the strategy. These "all-in-one", synthetically accessible RAFT agents allow highly controlled preparation of synthetic peptide-polymer conjugates and subsequent quantification of their delivery into cells.
Topics: Polymers; Cell-Penetrating Peptides; Lysine; Acrylamide; Styrene
PubMed: 37695265
DOI: 10.1021/acsmacrolett.3c00460