The structural and functional properties of hemp protein isolate-epigallocatechin-3-gallate biopolymer covalent complex during heating.

BACKGROUND: It is well known that hemp proteins have the disadvantages of poor solubility and poor emulsification. To improve these shortcomings, an alkali covalent cross-linking method was used to prepare hemp protein isolate-epigallocatechin-3-gallate biopolymer (HPI-EGCG) and the effects of different heat treatment conditions on the structure and emulsifying properties of the HPI-EGCG covalent complex were studied. RESULTS: The secondary and tertiary structures, solubility, and emulsification ability of the HPI-EGCG complexes were evaluated using particle size, zeta potential, circular dichroism (CD), and fluorescence spectroscopy indices. The results showed that the absolute value of zeta potential of HPI-EGCG covalent complex was the largest, 18.6 mV, and the maximum binding amount of HPI to EGCG was 29.18 µmol g-1 . Under heat treatment at 25-35 °C, the α-helix content was reduced from 1.87% to 0%, and the ß-helix content was reduced from 82.79% to 0% after the covalent binding of HPI and EGCG. The solubility and emulsification properties of the HPI-EGCG covalent complexes were improved significantly, and the emulsification activity index (EAI) and emulsion stability index (ESI) were increased by 2.77-fold and 1.21-fold, respectively. CONCLUSION: A new HPI-EGCG covalent complex was developed in this study to provide a theoretical basis for the application of HPI-EGCG in food industry. © 2023 Society of Chemical Industry.

Pro-inflammatory cytokines induce odontogenic differentiation of dental pulp-derived stem cells.

Postnatal dental pulp stem cells (DPSCs) represent a unique precursor population in the dental pulp, which have multipotential and harbor great potential for tissue engineering purposes. However, for therapy applications, transplanted cells are often exposed to unfavorable conditions such as cytokines released from necrotic or inflammatory cells in injured tissues. It is not clear how stem cells exposed to these conditions changes in their characteristics. In this study, the effects of pro-inflammatory cytokines, such as IL-1 and TNF, on DPSCs were investigated. Cells were treated with IL-1, TNF, or both for 3, 7, and 12 days. The cultures were evaluated for cell proliferation, ALP activity, and real-time PCR. We found that a short treatment (3 days) of pro-inflammatory cytokines induced the odontogenic differentiation of DPSCs. Furthermore, post 3 days treatment with pro-inflammatory cytokines, the cell-scaffold complexes were implanted subcutaneously in mice for 8 weeks. Histological analysis demonstrated that the cultures gave obviously mineralized tissue formation, especially for both IL-1 and TNF applied. These data suggest that IL-1 and TNF produced in the early inflammatory reaction may induce the mineralization of DPSCs.

Chitosan/collagen scaffold containing bone morphogenetic protein-7 DNA supports dental pulp stem cell differentiation in vitro and in vivo.

In this study, porous chitosan/collagen scaffolds were prepared through a freeze-drying process, and loaded with the plasmid vector encoding human bone morphogenetic protein-7 (BMP-7) gene. To investigate the feasibility and efficacy of this gene-activated scaffold on dental tissue engineering, human dental pulp stem cells (DPSCs) were seeded in this scaffold for in vitro and in vivo study. In vitro results indicated that cells can be transfected successfully by loaded plasmid and secrete BMP-7 until day 24. Evaluation of DNA content, ALP activity, calcium content, SEM, and real-time PCR revealed that cells on gene-activated scaffold showed better proliferation properties and odontoblastic differentiation behaviors than cells on pure scaffolds. Then, these cell-scaffold complexes were implanted subcutaneously and retrieved after 4 weeks for histology evaluation. In vivo results that gene-activated scaffold group could still trace the existence of tranfected cells at week 4 and showed the upregulated expression of DSPP compared to pure scaffold groups. On the basis of our results, chitosan/collagen-loaded BMP-7 DNA appears to be an effective substrate candidate for gene delivery and indeed enhanced DPSCs differentiation toward an odontoblast-like phenotype in vitro and in vivo. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.

Photoacoustic Imaging-Trackable Magnetic Microswimmers for Pathogenic Bacterial Infection Treatment.

Micro/nanorobots have been extensively explored as a tetherless small-scale robotic biodevice to perform minimally invasive interventions in hard-to-reach regions. Despite the emergence of versatile micro/nanorobots in recent years, matched in vivo development remains challenging, limited by unsatisfactory integration of core functions. Herein, we report a polydopamine (PDA)-coated magnetic microswimmer consisting of a magnetized Spirulina (MSP) matrix and PDA surface. Apart from the properties of the existing MSP (e.g., robust propulsion, natural fluorescence, tailored biodegradation, and selective cytotoxicity), the introduced PDA coating enhances the photoacoustic (PA) signal and photothermal effect of the MSP, thus making PA image tracking and photothermal therapy possible. Meanwhile, the PDA's innate fluorescence quenching and diverse surface reactivity allows an off-on fluorescence diagnosis with fluorescence probes (e.g., coumarin 7). As a proof of concept, real-time image tracking (by PA imaging) and desired theranostic capabilities of PDA-MSP microswimmer swarms are demonstrated for the treatment of pathogenic bacterial infection. Our study suggests a feasible antibacterial microrobot for in vivo development and a facile yet versatile functionalization strategy of micro/nanorobots.

The maintenance of an oral epithelial barrier.

Oral epithelial barrier consists of closely controlled structure of the stratified squamous epithelium, which is the gateway to human bodies and encounters a huge burden of microbial, airborne and dietary antigens, as well as masticatory damage. Once this barrier is destroyed, it will trigger bone loss, tissue damage and microbial dysbiosis and lead to diseases, such as periodontitis, oral mucosal diseases and oral cancer. Recently, increasing evidences showed that different factors including microorganism, saliva, proteins and immune components have been considered to play a critical role in the disruption of oral epithelial barrier. Herein, we discussed mechanisms governing the maintenance of oral epithelial barrier. Besides, the role of oral epithelial barrier failure in oral carcinogenesis will also be talked about.

Bacteria-Responsive Nanoliposomes as Smart Sonotheranostics for Multidrug Resistant Bacterial Infections.

Rapid emergence of multidrug resistant (MDR) "superbugs" poses a severe threat to global health. Notably, undeveloped diagnosis and concomitant treatment failure remain highly challenging. Herein, we report a sonotheranostic strategy to achieve bacteria-specific labeling and visualized sonodynamic therapy (SDT). Using maltohexaose-decorated cholesterol and bacteria-responsive lipid compositions, a smart nanoliposomes platform (MLP18) was developed for precise delivery of purpurin 18, a potent sonosensitizer proved in this study. Taking advantage of the bacteria-specific maltodextrin transport pathway, the prepared MLP18 can specifically target the bacterial infection site and accurately distinguish the foci from sterile inflammation or cancer with a highly selective fluorescence/photoacoustic signal on the bacteria-infected site of mice. Moreover, the bacteria-responsive feature of MLP18 activated an efficient release and internalization of high concentration sonosensitizer into bacterial cells, resulting in effective sonodynamic elimination of MDR bacteria. In situ MRI monitoring visualized such potent sonodynamic activity and indicated that MLP18-mediated SDT could successfully eradicate inflammation and abscess from mice with bacterial myositis. In view of the above advantages, the developed nanoliposomes may serve as a promising sonotheranostic platform against MDR bacteria in the areas of healthcare.

Porphyromonas gingivalis Promotes 4-Nitroquinoline-1-Oxide-Induced Oral Carcinogenesis With an Alteration of Fatty Acid Metabolism.

Microbiota has been widely considered to play a critical role in human carcinogenesis. Human papilloma virus, hepatitis B and C virus, and Helicobacter pylori are implicated in the pathogenesis of cancer of uterine cervix, liver, and stomach, respectively. However, whether Porphyromonas gingivalis (P. gingivalis), a common Gram negative oral bacteria, is associated with oral carcinogenesis still remains unclear and its underlying mechanism needs to be addressed. Here, we established a combined experimental system of 4NQO-induced oral carcinoma model and chronic periodontitis model and investigated the effects of P. gingivalis infection on oral carcinogenesis and fatty acid metabolism during oral carcinogenesis. The data showed that in this animal model, P. gingivalis infection induced mice periodontitis, increased the tongue lesion size and multiplicity of each mouse and promoted oral cancer development. P. gingivalis treatment significantly increased the level of free fatty acids and altered the fatty acid profile in tongue tissues and the serum of mice. And P. gingivalis induced the formation of fatty liver of the mice. Besides, immunohistochemical analysis and qRT-PCR showed that the expression of fatty-acid synthase and acetyl-CoA carboxylase 1 were increased in the tongue and liver tissues of 4NQO-treated mice infected with P. gingivalis. These results showed that P. gingivalis promoted oral carcinogenesis and aggravated disturbance of fatty acid metabolism, indicating a close association among P. gingivalis, lipid metabolic and oral carcinogenesis.

Recent progresses in bioadhesive microspheres via transmucosal administration.

Based on the advantages of adhesion preparations and the application status of microspheres (MSs) in mucous delivery, this paper primarily reviews the bioadhesive MSs via transmucosal administration routes, including the mucosa in alimentary tract and other lumens. Particularly, the detailed researches about of celladhesive MSs and some new-style bioadhesive MSs are mentioned. Furthermore, this review attempts to reveal the advances of bioadhesive MSs as cell-selective bioadhesion systems and the stimuli-responsive MSs as location-specific drug delivery systems. Although these MSs show powerful strength, some far-sighted ideas should be brought on agendas. In the future, mechanisms should be put under tight scrutiny and more attention should be focused on the excellent bioadhesive materials and the 'second generation mucoadhesives'. Meaningful clinical applications of these novel MSs are also of current concerns and need more detailed researches.

pH-responsive polymer-drug conjugates: Design and progress.

Polymer-drug conjugates are becoming established as a shining platform for drug delivery. Incorporation of pH-responsive linker between drug and polymer is expected to realize triggered release of bioactive agents from conjugates in specific sites, either in mildly acidic extracellular matrices of tumor tissues or, after cellular internalization, in acidic endosomes and lysosomes. As an emerging drug delivery system, such pH-responsive polymer-drug conjugates are able to selectively deliver and activate drug molecules while reducing their systemic side-effects. In this review, we present the recent advances in pH-responsive polymer-drug conjugates with different chemical structures and architectures, and attempt to clarify their mechanism of action, synthesis and characterization technology. Furthermore, several promising approaches for the future will also be suggested.

Polymer-drug conjugates: recent progress on administration routes.

INTRODUCTION: Polymer-drug conjugates are an important part of polymer therapeutics. Recently, they have been used as an appealing platform for drug delivery. As a delivery vector, the route of administration performs a serious impact on the accessibility of drug molecules to their respective target site and therapeutic index. Furthermore, the physicochemical and biological properties of conjugates also correlate distinctly with the route of administration. AREAS COVERED: This article reviews the recent advances of polymer-drug conjugates as drug delivery systems through parenteral, enteral and topical routes. In particular, it mainly focuses on the classical and emerging routes such as injection, oral, transdermal, pulmonary and ocular routes using polymer-drug conjugates as delivery systems. EXPERT OPINION: Although polymer-conjugated drug delivery systems reported so far face severe shortcoming of being incomplete methodology and limited routes for administration (mostly concentrated in injection), some polymer carriers like poly(amidoamine) and hyaluronic acid still offer an appealing platform to deliver drug. Acquiring the particular characteristics of each polymer carrier, exploiting novel biodegradable polymer, expanding classical drug administration ways by emerging routes and developing a rational and systematic methodology to design administration routes will be the promising directions.

The synthesis, self-assembling, and biocompatibility of a novel O-carboxymethyl chitosan cholate decorated with glycyrrhetinic acid.

O-carboxymethyl chitosan (OCMC) was firstly decorated with cholic acid (CA) to acquire an amphiphilic polymer under alkaline condition. Then glycyrrhetinic acid (GA) was conjugated to the polymer via a succinate linker and finally treated with NaCO3 solution to obtain new conjugates for potential liver targeted delivery. These conjugates formed uniform aggregates with low critical aggregation concentrations (0.028-0.079 mg/mL) in PBS. The average diameter of cholic acid modified carboxymethyl chitosan (CMCA) aggregates (110-257 nm) decreased with the increase of CA substitution degree and became slightly larger after GA modification. Negative zeta potential (-15 mV) of GA decorated CMCA (GA-CMCA) revealed that the formation of negatively charged shells and spherical morphology was observed under transmission electron microscopy. Furthermore, hemolysis test, in vitro cytotoxicity assay and cellular uptake study all demonstrated the safety and feasibility of these conjugates as a promising carrier for liver targeted drug delivery.

Development of a folate-modified curcumin loaded micelle delivery system for cancer targeting.

Targeted drug delivery system for tumor cells is an appealing platform on enhancing the therapeutic effects and reducing the side effects of the drug. In this study, we developed folate-modified curcumin (Cur) loaded micelles (Cur-FPPs) for cancer chemotherapy. The targeting material, Folate-PEG3000-PLA2000, was synthesized by the amide bond formation reaction. And the Cur loaded micelles were prepared by thin-film hydration method with mPEG2000-PLA2000 (Cur-PPs) or mPEG2000-PLA2000 and Folate-PEG3000-PLA2000 (Cur-FPPs) as carrier. A central composite design (CCD) was used to optimize the formulation, and the optimized Cur-FPPs was prepared with the weight ratio of Folate-PEG3000-PLA2000 and mPEG2000-PLA2000 at 1:9. The average size of the mixed micelles was 70nm, the encapsulating efficiency and drug-loading were 80.73±0.16% and 4.84±0.01%, respectively. Compared with the Cur propylene glycol solution, the in vitro release of Cur from Cur-FPPs showed a sustained manner. Furthermore, the in vitro cytotoxicity and cellular uptake of Cur-FPPs were significantly enhanced towards MCF-7 and HepG2 cells. The pharmacokinetic studies in rats indicated that a 3-fold increase in the half-life was achieved for Cur loaded micelle formulations relative to solubilized Cur. All the results demonstrated that folate-modified Cur micelles could serve as a potential nanocarrier to improve the solubility and anti-cancer activity of Cur.

Polymer-drug conjugates: present state of play and future perspectives.

Polymer conjugation is an efficient approach to improve therapeutic properties of drugs and biological agents. Since the first synthetic polymer-drug conjugate entered clinical trials in 1994, this technology has undergone notable development for the introduction and study of novel polymers and for the progress in the biological rationale for designing conjugates. Not surprisingly, new polymers, in addition to the best known polyethylene glycol, poly[N-(2-hydroxypropyl)methacrylamide], are continuously conjugated with drugs to achieve biodegradable, stimuli-sensitive and targeted systems in an attempt to prolong blood circulation times and enhance drug concentrations at the intended site of action. This overview focuses on bioconjugates of water-soluble polymers with low molecular weight drugs. Additionally, the most recent achievements in the polymer-drug conjugate field and several promising approaches for the future are discussed.

WITHDRAWN: The mesenchymal stem cell potential of human dental pulp derived cells transfected with embryonic transcription factor Oct-4.

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Mineralized tissue formation by bone morphogenetic protein-7-transfected pulp stem cells.

INTRODUCTION: Recombinant human bone morphogenetic protein-7 (BMP-7) is a well-established agent to induce bone and dentin formation. Little is understood until now whether BMP-7 could be used to genetically modify human dental pulp stem cells for tissue engineering applications. METHODS: This study was to determine the feasibility of mineralized tissue formation from human dental pulp-derived stem cells (DPSCs) transfected with adenoviral-mediated human BMP-7 gene through in vitro and in vivo evaluations. RESULTS: In vitro results of alkaline phosphatase, calcium content, and real-time polymerase chain reaction showed that BMP-7-transfected cells had the ability to differentiate towards the odontoblast phenotype and produce a calcified extracellular matrix. Transfected cell were seeded onto a porous ceramic scaffold and implanted subcutaneously in mice. Samples were retrieved after 4 and 8 weeks for histology evaluation. The results indicated that only the cultures with BMP-7 gene transfection showed obvious hard-tissue generation. CONCLUSIONS: Our data suggest that adenovirus-mediated BMP-7 expression can induce odontogenic differentiation of human DPSCs and show effectively mineralized tissue formation in vivo, which may provide support for gene therapy candidate of BMP-7 in dental tissue engineering.

Electrophoretic deposition of hydroxyapatite-CaSiO3-chitosan composite coatings.

Electrophoretic deposition (EPD) method has been developed for the fabrication of hydroxyapatite (HA)-CaSiO(3) (CS)-chitosan composite coatings for biomedical applications. The use of chitosan enabled the co-deposition of HA and CS particles and offered the advantage of room temperature processing of composite materials. The coating composition was varied by the variation of HA and CS concentrations in the chitosan solutions. Cathodic deposits were obtained as HA-CS-chitosan monolayers, HA-chitosan/chitosan multilayers or functionally graded materials (FGM) containing HA-chitosan and CS-chitosan layers of different composition. The thickness of the individual layers was varied in the range of 0.1-20 microm. The deposition yield was studied at different experimental conditions and compared with the results of modeling. It was shown that the moving boundary model for the two component system can explain the non-linear increase in the deposition yield with increasing HA concentration in chitosan solutions. The obtained coatings were studied by thermogravimetric analysis (TGA), differential thermal analysis (DTA) and scanning electron microscopy (SEM). Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) studies showed that these coatings provided corrosion protection of stainless steel substrates in Ringer's physiological solution. The deposition mechanism and kinetics of deposition have been discussed.

[Correlation of HBV genotypes to the therapeutic effect of PEG-interferon and the pathological changes of the liver of chronic hepatitis B patients].

OBJECTIVE: To study the correlation of HBV genotypes to the response to PEG-interferon alpha (PEG-IFN) in chronic hepatitis B (CHB) patients. METHODS: Real-time fluorescent PCR was used for HBV genotyping in 48 CHB patients, and the therapeutic effects of PEG-IFN and hepatic pathological changes were observed. RESULTS: No obvious differences were noted in ALT and HBV DNA levels or negative rate for HBeAg between patients with genotypes B and C (P>0.05). The sustained response rate was significantly higher in genotype B than in genotype C patients 48 weeks o after the therapy. CONCLUSION: HBV genotype is the main factor for predicting PEG-IFN therapy response in CHB patients, and the sustained response rate is significantly higher in genotype B than in genotype C patients.