Sialic Acid-Functionalized Pyroptosis Nanotuner for Epigenetic Regulation and Enhanced Cancer Immunotherapy.

The efficacy of immune checkpoint blockade (ICB) in promoting an immune response against tumors still encounters challenges such as low response rates and off-target effects. Pyroptosis, an immunogenic cell death (ICD) mechanism, holds the potential to overcome the limitations of ICB by activating and recruiting immune cells. However, the expression of the pyroptosis-related protein Gasdermin-E(GSDME) in some tumors is limited due to mRNA methylation. To overcome this obstacle, sialic acid-functionalized liposomes coloaded with decitabine, a demethylation drug, and triclabendazole, a pyroptosis-inducing drug are developed. This nanosystem primarily accumulates at tumor sites via sialic acid and the Siglec receptor, elevating liposome accumulation in tumors up to 3.84-fold at 24 h and leading to the upregulation of pyroptosis-related proteins and caspase-3/GSDME-dependent pyroptosis. Consequently, it facilitates the infiltration of CD8+ T cells into the tumor microenvironment and enhances the efficacy of ICB therapy. The tumor inhibition rate of the treatment group is 89.1% at 21 days. This study highlights the potential of sialic acid-functionalized pyroptosis nanotuners as a promising approach for improving the efficacy of ICB therapy in tumors with low GSDME expression through epigenetic alteration and ICD.

In Vivo Dual-Modality Fluorescence and Magnetic Resonance Imaging-Guided Lymph Node Mapping with Good Biocompatibility Manganese Oxide Nanoparticles.

Multifunctional manganese oxide nanoparticles (NPs) with impressive enhanced T1 contrast ability show great promise in biomedical diagnosis. Herein, we developed a dual-modality imaging agent system based on polyethylene glycol (PEG)-coated manganese oxide NPs conjugated with organic dye (Cy7.5), which functions as a fluorescence imaging (FI) agent as well as a magnetic resonance imaging (MRI) imaging agent. The formed Mn3O4@PEG-Cy7.5 NPs with the size of ~10 nm exhibit good colloidal stability in different physiological media. Serial FI and MRI studies that non-invasively assessed the bio-distribution pattern and the feasibility for in vivo dual-modality imaging-guided lymph node mapping have been investigated. In addition, histological and biochemical analyses exhibited low toxicity even at a dose of 20 mg/kg in vivo. Since Mn3O4@PEG-Cy7.5 NPs exhibited desirable properties as imaging agents and good biocompatibility, this work offers a robust, safe, and accurate diagnostic platform based on manganese oxide NPs for tumor metastasis diagnosis.

Study on the Antibacterial Activity and Bone Inductivity of Nanosilver/PLGA-Coated TI-CU Implants.

Background: Implants are widely used in the field of orthopedics and dental sciences. Titanium (TI) and its alloys have become the most widely used implant materials, but implant-associated infection remains a common and serious complication after implant surgery. In addition, titanium exhibits biological inertness, which prevents implants and bone tissue from binding strongly and may cause implants to loosen and fall out. Therefore, preventing implant infection and improving their bone induction ability are important goals. Purpose: To study the antibacterial activity and bone induction ability of titanium-copper alloy implants coated with nanosilver/poly (lactic-co-glycolic acid) (NSPTICU) and provide a new approach for inhibiting implant-associated infection and promoting bone integration. Methods: We first examined the in vitro osteogenic ability of NSPTICU implants by studying the proliferation and differentiation of MC3T3-E1 cells. Furthermore, the ability of NSPTICU implants to induce osteogenic activity in SD rats was studied by micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, masson staining, immunohistochemistry and van gieson (VG) staining. The antibacterial activity of NSPTICU in vitro was studied with gram-positive Staphylococcus aureus (Sa) and gram-negative Escherichia coli (E. coli) bacteria. Sa was used as the test bacterium, and the antibacterial ability of NSPTICU implanted in rats was studied by gross view specimen collection, bacterial colony counting, HE staining and Giemsa staining. Results: Alizarin red staining, alkaline phosphatase (ALP) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis showed that NSPTICU promoted the osteogenic differentiation of MC3T3-E1 cells. The in vitro antimicrobial results showed that the NSPTICU implants exhibited better antibacterial properties. Animal experiments showed that NSPTICU can inhibit inflammation and promote the repair of bone defects. Conclusion: NSPTICU has excellent antibacterial and bone induction ability, and has broad application prospects in the treatment of bone defects related to orthopedics and dental sciences.

An injectable thermosensitive hyaluronic acid/pluronic F-127 hydrogel for deep penetration and combination therapy of frozen shoulder.

Frozen shoulder (FS) is a common and progressive shoulder disorder that causes glenohumeral joint stiffness, characterized by inflammation and fibrosis. The treatment options are quite limited, and the therapeutic response is hindered by the fibrous membrane formed by excessive collagen and the rapid removal by synovial fluid. To address these challenges, we designed a hyaluronic acid/Pluronic F-127 (HP)-based injectable thermosensitive hydrogel as a drug carrier loaded with dexamethasone and collagenase (HPDC). We screened for an optimal HP hydrogel that can sustain drug release for approximately 10 days both in vitro and in vivo. In the meanwhile, we found that HP hydrogel could inhibit the proliferation and diminish the adhesion capacity of rat synovial cells induced by transforming growth factor-ß1. Furthermore, using an established immobilization rat model of FS, intra-articular injection of HPDC significantly improved joint range of motion compared to medication alone. Relying on sustained drug release, the accumulated collagen fibers were degraded by collagenase to promote the deep delivery of dexamethasone. These findings showed a positive combined treatment effect of HPDC, providing a novel idea for the comprehensive treatment of FS.

[Analysis of material preparation, anti-bacterial activity of Porphyromonas gingivalis and cell bioassays of TiO2-PEEK-CRGDS].

PURPOSE: To modify polyetheretherketone(PEEK) composite material with nanometer titanium dioxide (TiO2) and CRGDS peptide to prepare TiO2-PEEK-CRGDS, and evaluate its anti- activity of Porphyromonas gingivalis and effect on cell activity. METHODS: TiO2-PEEK was prepared by plasma immersion ion implantation(PⅢ), then immersed into gelatin solution of pentapeptides of CRGDS, and freeze-dried. The same diameter and thickness of PEEK was set as control. Scanning electron microscope (SEM) was used to observe the three-dimensional topography and roughness on the surface of the specimen, colony count was calculated to evaluate the survival of Porphyromonas gingivalis, living/dead cell count was used to detect the activity of human gingival fibroblasts(HGFs), CCK-8 assay was used to detect the proliferation ability of HGFs. The quantitative data was indicated as and analyzed by using GraphPad Prism 7.0 software package. RESULTS: The antibacterial rates of PEEK, TiO2-PEEK and TiO2-PEEK-CRGDS were 40.3%, 57.2% and 60.3%, respectively. At 12 days, the ability of TiO2-PEEK-CRGDS to promote the growth of human gingival fibroblasts was significantly different from that of the TiO2-PEEK and PEEK group(P＜0.05). CONCLUSIONS: The optimized TiO2-PEEK-CRGDS has better hydrophilicity than pure titanium and PEEK, and can significantly promote the proliferation of gingival fibroblasts.

Biosynthesized Quantum Dots as Improved Biocompatible Tools for Biomedical Applications.

Quantum Dots (QDs), whose diameters are often limited to 10 nm, have been of interest to researchers for their unique optical characteristics, which are attributed to quantum confinement. Following their early application in the electrical industry as light-emitting diode materials, semiconductor nanocrystals have continued to show great potential in clinical diagnosis and biomedical applications. The conventional physical and chemical pathways for QD syntheses typically require harsh conditions and hazardous reagents, and these products encounter non-hydrophilic problems due to organic capping ligands when they enter the physiological environment. The natural reducing abilities of living organisms, especially microbes, are then exploited to prepare QDs from available metal precursors. Low-cost and eco-friendly biosynthesis approaches have the potential for further biomedical applications which benefit from the good biocompatibility of protein-coated QDs. The surface biomass offers many binding sites to modify substances or target ligands, therefore achieving multiple functions through simple and efficient operations. Biosynthetic QDs could function as bioimaging and biolabeling agents because of their luminescence properties similar to those of chemical QDs. In addition, extensive research has been carried out on the antibacterial activity, metal ion detection and bioremediation. As a result, this review details the advanced progress of biomedical applications of biosynthesized QDs and illustrates these principles as clearly as possible.

Galectin-1 Inhibited LPS-Induced Autophagy and Apoptosis of Human Periodontal Ligament Stem Cells.

Periodontitis is a widespread human chronic inflammatory disease of the tooth-surrounding tissues, which induces the destruction of periodontium and pathologic loss of teeth among adults. It has been reported that interleukin (IL)-17 was significantly increased in periodontitis patients compared to controls, while galectin-1 (Gal-1) was lower. Interestingly, it is found that Gal-1 treatment reduced systemic IL-17 levels. Hence, the aim of the present study was to explore the effect of Gal-1 on periodontitis development and investigate its underlying mechanism. In this study, Gal-1 was poorly expressed in lipopolysaccharide (LPS)-induced human periodontal ligament stem cells (hPDLSCs), and Gal-1 overexpression attenuated the production of inflammatory cytokines induced by LPS. Moreover, Gal-1 overexpression alleviated LPS-induced cell autophagy and apoptosis and reduced the expressions of IL-17A and IL-17R. Interestingly, IL-17A reversed the effect of Gal-1 on cell autophagy, inflammation, and cell apoptosis induced by the LPS challenge. In conclusion, Gal-1 inhibited LPS-induced autophagy and apoptosis of hPDLSC via regulation of IL-17A expression. Therefore, Gal-1 may have promising potential in regenerating periodontium.

Synthesis of bimetallic silver-gold nanoparticle composites using a cellulose dope: Tunable nanostructure and its biological activity.

Introducing functional metal nanoparticles (NPs) into flexible substrate is being increasingly attempted to expand their application. Here, we extend the synthesis of cellulose to its unmodified dope achieving freestanding nanocomposite decorated with bimetallic Ag-Au NPs through the one pot reaction. In the procedure, cellulose chain not only acts as a reducing agent but also a biocompatible support for NPs with a mean size of 7.9-9.7 nm. Meanwhile, changing the addition order of Ag+ and AuCl4- generated different atom arrangement in the bimetallic NPs. Moreover, the correlation of bioactivity to NP atom arrangement was studied. The result revealed that the nanocomposite containing NPs with an ultrathin Ag-rich outermost shell around an Au-rich core showed better bactericidal ability while lower cytotoxicity. In addition, the nanocomposite exhibited a sensitive SERS property for determination of R6G with a high enhancement factor of 108.

EZH2 promotes DNA replication by stabilizing interaction of POLδ and PCNA via methylation-mediated PCNA trimerization.

BACKGROUND: Proliferating cell nuclear antigen (PCNA), a ring-shaped homotrimer complex, promotes DNA replication via binding to DNA polymerase. Trimerized PCNA is critical for DNA replication. Enhancer of zeste homologue 2 (EZH2), which primarily acts as a histone methyltransferase, is essential for proliferation. However, how EZH2 promotes proliferation by controlling DNA replication through PCNA remains elusive. RESULTS: Here, we showed that low EZH2 levels repressed the proliferation of human dental pulp cells (hDPCs). The EZH2 protein level was dramatically upregulated in hDPCs at S phase in the absence of H3K27 trimethylation. Molecularly, EZH2 interacted with PCNA via the PIP box and dimethylated PCNA at lysine 110. Dimethylation of PCNA is essential for stabilization of the PCNA trimer and the binding of DNA polymerase δ to PCNA. CONCLUSIONS: Our data reveal the direct interaction between PCNA and EZH2 and a novel mechanism by which EZH2 orchestrates genome duplication.

Three-dimensional cellulose based silver-functionalized ZnO nanocomposite with controlled geometry: Synthesis, characterization and properties.

Cellulose based Ag-functionalized ZnO nanocomposite (AZC) films were prepared using a green and easy scale-up strategy. Firstly, ZnO embedded cellulose (ZC) nanocomposite was synthesized from a cellulose-NaOH/zincate/urea solution through a biomimetic approach. Secondly, Ag nanoparticles (NPs) with a mean diameter of 53.2 nm were efficiently deposited onto the surface of embedded ZnO in cellulose matrix under UV irradiation (16 w), yielding the multi-hybrid AZC film. Owing to the porous structure of cellulose substrate and its rich hydroxyl group, the NPs in the ACZ films displayed good stability. Because of the formation of Schottky barriers in the Ag-ZnO regions, the catalytic activity of ACZ films increased by 20 times when compared to that of ZC sample. Furthermore, the AZC films could completely inhibit both S. aureus and E. coli growth. This facile and eco-friendly approach is expected to pave the way for constructing multifunctional cellulose material for various niche applications.

[Clinical efficacy and effects of CAD/CAM zirconia all-ceramic crown and metal-ceramic crown restoration on periodontal tissues].

PURPOSE: To investigate the clinical efficacy and effects of CAD/CAM zirconia all-ceramic crown, cobalt-chromium alloy and silver-palladium alloy porcelain-fused-to-metal crown restorations on periodontal tissues. METHODS: Forty-nine teeth with crowns in 46 patients were randomly assigned into CAD/CAM zirconia all-ceramic crown group, cobalt-chromium alloy porcelain-fused-to-metal crown group and silver-palladium alloy porcelain-fused-to-metal crown group. The amounts of GCF, TNF-α and IL-6 were analyzed before and 12 months after restorations, and the clinical efficacy was evaluated. RESULTS: Comparing the clinical efficacy within 3 groups, indicators such as color match and the status of gums in CAD/CAM zirconia all-ceramic crown group were significantly better than other 2 groups (P<0.05). The amounts of GCF, TNF-α and IL-6 in CAD/CAM zirconia all-ceramic crown group were also significantly better than other 2 groups (P<0.01). CONCLUSIONS: CAD/CAM zirconia all-ceramic crown restoration had better clinical efficacy than cobalt-chromium alloy and silver-palladium alloy porcelain-fused-to-metal crown restorations with no apparently damage to periodontal tissues.

[Application of Nd:YAP laser in dental pulp revascularization].

PURPOSE: To compare the effect of Nd:YAP laser and Hoshino's triple antibiotic paste on root canal disinfection in the treatment of pulp revascularization, and to provide reference for root canal disinfection in dental pulp revascularization. METHODS: Forty immature permanent teeth diagnosed as acute or chronic periapical periodontitis were included. The periapical lesions and root development were recorded. The cases were divided into 2 groups: the control group and the Nd:YAP laser disinfection experimental group. Clinical examination and X-ray evaluation of each case were performed after treatment. Statistical analysis was performed using SPSS 19.0 software package. RESULTS: Two cases showed symptoms in control group 1 week after treatment, while 4 cases had symptoms in the experimental group. The clinical symptoms disappeared in the control group 2 weeks after treatment, while 1 case still had symptoms in the experimental group. There was no significant difference between the two groups (P>0.05). Clinical evaluation at 18 months of follow-up showed that 2 and 3 cases had recurrent symptoms in the control group and the experimental group, respectively; continuous development of the root was noted in 12 and 10 cases on X-ray film in the control and experimental group, respectively, while 3 and 4 teeth had no obvious root development in the control and experimental group, respectively. There was no significant difference between the control group and the experimental group (P>0.05). CONCLUSIONS: Nd:YAP laser can be used for effective root canal disinfection without obvious effect on the prognosis of dental pulp revascularization.

[Influence of root canal working length on the clinical effect evaluated by periapical radiography and cone-beam computed tomography].

PURPOSE: The verification of the best length of root canal instrumentation and obturation is still controversial in endodontics. The purpose of this study was to determine the influence of root canal working length on the clinical effect evaluated by periapical radiography and cone-beam computed tomography (CBCT). METHODS: A total of 503 root canal obturations were evaluated by using periapical radiography and CBCT. Distances from the radiographic apex to the tip of filling material were measured and classified as 1-2 mm, less than 1 mm, beyond apex, and at the apex. Odds ratio, confidence intervals, and Chi-square test were used for statistical analyses with SPSS 13.0 software package. RESULTS: Periapical radiographs showed that root canal obturations were 1-2 mm short of the apex in 88%, 89.3%, and 95% of the anterior teeth, premolars, and molars, respectively. CBCT images showed obturations had the same length in 70%, 73.7%, and 79% of anterior teeth, premolars, and molars, respectively. The frequency of AP was significantly greater in molars than in the other tooth, regardless of diagnostic tools. AP was detected more frequently when CBCT was used. CONCLUSIONS: AP is detected at all lengths of root canal obturation. The analysis of diagnostic methods show that AP is detected more frequently using CBCT.

[Comparative studies on cariogenic bacteria of the root surface before and after post-core crown restoration in aged people].

OBJECTIVE: To investigate the changes in the quantity of colonizing Streptococcus mutans(S. mutans) and Actinomyces on the root surface plaque before and after post-core crown restoration of the mandibular first molars in the elderly patients. METHODS: A total of 30 elderly patients, each with one post-core crown restoration of the mandibular first molar, were randomly chosen to participate in the studies. Patients with mandibular first molars with post-core crown restoration and those with healthy contralateral mandibular first molars were divided into the test and control groups, respectively. Root surface plaques of the two groups were collected before tooth preparation, 72 h after preparation, one week after preparation, and one month after restoration. S. mutans, Actinomyces naeslundii (A. naeslundii) and Actinomyces viscosus (A. viscosus), were identified using colony morphology, biochemical techniques, and polymerase chain reaction (PCR). Plaque count was measured using microbial colony count. RESULTS: The number of S. mutans and A. viscosus and A. naeslundii in the test group, which was statistically significant (P<0.05), increased 72 h after preparation. The quantities of S. mutans, A. viscosus, and A. naeslundii one week after preparation were significantly different (P<0.05). The plaque count of S. mutans, A. viscosus, and A. naeslundii in the test group decreased one month after restoration (P<0.05). CONCLUSION: The quantities of S. mutans, A. viscosus and A. naeslundii increase one week after preparation but decrease one month after restoration. The finding suggests that dentists should educate patients about plaque control during the early period after tooth preparation.