Electrospun L-Lysine/Amorphous Calcium Phosphate Loaded Core-Sheath Nanofibers for Managing Oral Biofilm Infections and Promoting Periodontal Tissue Repairment.

Introduction: Periodontitis, a chronic inflammatory disease prevalent worldwide, is primarily treated through GTR for tissue regeneration. The efficacy of GTR, however, remains uncertain due to potential infections and the intricate microenvironment of periodontal tissue. Herein, We developed a novel core-shell structure multifunctional membrane using a dual-drug-loaded coaxial electrospinning technique (Lys/ACP-CNF), contains L-lysine in the outer layer to aid in controlling biofilms after GTR regenerative surgery, and ACP in the inner layer to enhance osteogenic performance for accelerating alveolar bone repair. Methods: The biocompatibility and cell adhesion were evaluated through CCK-8 and fluorescence imaging, respectively. The antibacterial activity was assessed using a plate counting assay. ALP, ARS, and RT-qPCR were used to examine osteogenic differentiation. Additionally, an in vivo experiment was conducted on a rat model with acute periodontal defect and infection. Micro-CT and histological analysis were utilized to analyze the in vivo alveolar bone regeneration. Results: Structural and physicochemical characterization confirmed the successful construction of the core-shell fibrous structure. Additionally, the Lys/ACP-CNF showed strong antibacterial coaggregation effects and induced osteogenic differentiation of PDLSCs in vitro. The in vivo experiment confirmed that Lys/ACP-CNF promotes new bone formation. Conclusion: Lys/ACP-CNF rapidly exhibited excellent antibacterial activity, protected PDLSCs from infection, and was conducive to osteogenesis, demonstrating its potential application for clinical periodontal GTR surgery.

Injectable CNPs/DMP1-loaded self-assembly hydrogel regulating inflammation of dental pulp stem cells for dentin regeneration.

Vital pulp preservation, which is a clinical challenge of aseptic or iatrogenic accidental exposure of the pulp, in cases direct pulp capping is the main technology. Human dental pulp stem cells (hDPSCs) play a critical role in pulp tissue repair, but their differentiative ability could be inhibited by the potential infection and inflammatory response of the exposed pulp. Therefore, inflammatory regulation and differentiated promotion of hDPSCs are both essential for preserving living pulp teeth. In this study, we constructed a functional dental pulp-capping hydrogel by loading cerium oxide nanoparticles (CNPs) and dentin matrix protein-1 (DMP1) into an injectable Fmoc-triphenylalanine hydrogel (Fmoc-phe3 hydrogel) as CNPs/DMP1/Hydrogel for in situ drugs delivery. With a view to long-term storage and release of CNPs (anti-inflammatory and antioxidant) to regulate the local inflammatory environment and DMP1 to promote the regeneration of dentin. Results of CCK-8, LDH release, hemolysis, and Live/Dead assessment of cells demonstrated the good biocompatibility of CNPs/DMP1/Hydrogel. The levels of alkaline phosphatase activity, quantification of the mineralized nodules, expressions of osteogenic genes and proteins demonstrated CNPs/DMP1/Hydrogel could protect the activity of hDPSCs' osteogenic/dentinogenic differentiation by reducing the inflammation response via releasing CNPs. The therapy effects were further confirmed in rat models, CNPs/DMP1/Hydrogel reduced the necrosis rate of damaged pulp and promoted injured pulp repair and reparative dentin formation with preserved vital pulps. In summary, the CNPs/DMP1/Hydrogel composite is an up-and-coming pulp-capping material candidate to induce reparative dentin formation, as well as provide a theoretical and experimental basis for developing pulp-capping materials.

Six-year clinical evaluation of iRoot BP Plus as apical barrier in permanent teeth of periapical periodontitis.

The apical barrier technique in permanent teeth with extensive destruction of the periapical tissue and a long infection time is much more difficult to succeed, which is a clinical challenge. This study aimed to evaluate the long-term effects of iRoot BP Plus as an apical material in adult teeth. Fifty incisors and premolars were chosen for this study. All teeth were performed apical barrier with the same operator. After treatment, the teeth were clinically and radiographically evaluated at 1, 2 and 6 years. At the 1-year follow-up, 35 teeth had healed, and three patients developed an apical abscess due to root fracture at the 2-year follow-up. Six years postoperatively, one tooth showed root resorption, which was considered a failure. The long clinical evaluation confirmed that iRoot BP Plus is a suitable material for the apical barrier of mature teeth with open apices and periapical lesions.

Remodeling periodontal osteoimmune microenvironment through MAPK/NFκB phosphorylation pathway of macrophage via intelligent ROS scavenging.

Periodontitis is an inflammatory disorder which leads to the defect of tooth-supporting tissue, especially in alveolar bone. During this process, the polarization behavior of macrophages affects immune inflammation and bone regeneration in which reactive oxygen species (ROS) play an essential role. ROS level should be regulated to the physiological level to protect stem cells from the inflammatory immune microenvironment. Our previous study constructed a ROS-responsive nanoplatform (Pssl-NAC), which possessed ROS-responsive antioxidative effect and could be potentially applied in periodontitis. However, the connection among bone regeneration, inflammation and oxidative stress remained in osteoimmune regulation is not clear. To further investigate the mechanism of the way how Pssl-NAC works in the treatment of periodontitis would be meaningful. Here, we investigated the effect of PssL-NAC in the regulation of the osteoimmune microenvironment through macrophage polarization. Results show PssL-NAC regulated the macrophage polarization direction in an inflammatory environment by maintaining an appropriate level of intracellular ROS, in which the MAPK/NFκB phosphorylation pathway is particularly important. In the macrophage-human periodontal ligament stem cells (hPDLSCs) co-culture system, PssL-NAC treatment significantly enhanced the osteogenic differentiation of hPDLSCs. In vivo experiment further confirmed the M2-like macrophages increased in the periodontal tissue of rats, and the expression of iNOS and p65 decreased after PssL-NAC treatment. In conclusion, PssL-NAC regulates the osteoimmune microenvironment and protects stem cells from oxidative stress injury for bone regeneration, which provides a strategy for the treatment of periodontitis.

Ectopic expression of Camellia oleifera Abel. gibberellin 20-oxidase gene increased plant height and promoted secondary cell walls deposition in Arabidopsis.

MAIN CONCLUSION: Ectopic expression of Camellia oleifera Abel. gibberellin 20-oxidase 1 caused a taller phenotype, promoted secondary cell wall deposition, leaf enlargement, and early flowering, and reduced chlorophyll and anthocyanin accumulation and seed enlargement phenotype in Arabidopsis. Plant height and secondary cell wall (SCW) deposition are important plant traits. Gibberellins (GAs) play important roles in regulating plant height and SCWs deposition. Gibberellin 20-oxidase (GA20ox) is an important enzyme involved in GA biosynthesis. In the present study, we identified a GA synthesis gene in Camellia oleifera. The total length of the CoGA20ox1 gene sequence was 1146 bp, encoding 381 amino acids. Transgenic plants with CoGA20ox1 had a taller phenotype; a seed enlargement phenotype; promoted SCWs deposition, leaf enlargement, and early flowering; and reduced chlorophyll and anthocyanin accumulation. Genetic analysis showed that the mutant ga20ox1-3 Arabidopsis partially rescued the phenotype of CoGA20ox1 overexpression plants. The results showed that CoGA20ox1 participates in the growth and development of C. oleifera. The morphological changes in CoGA20ox1 overexpressed plants provide a theoretical basis for further exploration of GA biosynthesis and analysis of the molecular mechanism in C. oleifera.

Combined Black Phosphorus Nanosheets with ICG/aPDT is an Effective Anti-Inflammatory Treatment for Periodontal Disorders.

Introduction: Antibacterial photodynamic treatment (aPDT) has indispensable significance as a means of treating periodontal disorders because of its extraordinary potential for killing pathogenic bacteria by generating an overpowering amount of reactive oxygen species (ROS). The elevated ROS that may result from the antibacterial treatment procedure, however, could exert oxidative pressure inside periodontal pockets, causing irreparable damage to surrounding tissue, an issue that has severely restricted its medicinal applications. Accordingly, herein, we report the use of black phosphorus nanosheets (BPNSs) that can eliminate the side effects of ROS-based aPDT as well as scavenge ROS to produce an antibacterial effect. Methods: The antibacterial effect of ICG/aPDT was observed by direct microscopic colony counting. A microplate reader and confocal microscope enabled measurements of cell viability and the quantification of ROS fluorescence. BPNS administration regulated the oxidative environment. IL-1ß, IL-6, TNF-α, IL-10, TGF-ß, and Arg-1 mRNA expression levels were used to assess the inflammatory response after BPNS treatment. In vivo, the efficacy of the combination of BPNSs and ICG/aPDT was evaluated in rats with periodontal disease by histomorphometric and immunohistochemical analyses. Results: The CFU assay results verified the antibacterial effect of ICG/aPDT treatment, and ROS fluorescence quantification by CLSM indicated the antioxidative ability of the BPNSs. IL-1ß, IL-6, TNF-α, IL-10, TGF-ß, and Arg-1 mRNA expression levels were significantly decreased after BPNS treatment, confirming the in vitro anti-inflammatory effect of this nanomaterial. The histomorphometric and immunohistochemical analyses showed that the levels of proinflammatory factors decreased, suggesting that the BPNSs had anti-inflammatory effects in vivo. Conclusion: Treatment with antioxidative BPNSs gives new insights into future anti-inflammatory therapies for periodontal disease and other infection-related inflammatory illnesses and provides an approach to combat the flaws of aPDT.

Analysis of Camellia oleifera transcriptome reveals key pathways and hub genes involved during different photoperiods.

BACKGROUND: Camellia oleifera Abel. (C. oleifera) is an important traditional woody species in China that produces edible oil. However, the current literature lacks a proper understanding of C. oleifera's ability to adapt to different photoperiods. RESULTS: Our results indicate that the photoperiod can significantly impact flowering time in C. oleifera. We grew a total of nine samples under the short day condition (SD), middle day condition (MD) and long day condition (LD). Transcriptome analysis yielded 66.94 Gb of high-quality clean reads, with an average of over 6.73 Gb of reads for per sample. Following assembly, a total of 120,080 transcripts were obtained and 94,979 unigenes annotated. A total of 3475 differentially expressed genes (DEGs) were identified between the SD_MD, SD_LD, and MD_LD gene sets. Moreover, WGCNA identified ten gene modules. Genes in pink module (92 genes) were positively correlated with SD, and negatively correlated with both MD and LD. Genes in the magenta module (42 genes) were positively correlated with MD and negatively correlated with both LD and SD. Finally, genes in the yellow module (1758 genes) were positively correlated with both SD and MD, but negatively correlated with LD. KEGG enrichment analysis revealed that genes in the pink, magenta, and yellow modules were involved in flavonoid biosynthesis, amino sugar and nucleotide sugar metabolism and circadian rhythm pathways. Additionally, eight hub genes (GI, AP2, WRKY65, SCR, SHR, PHR1, ERF106, and SCL3) were obtained through network analysis. The hub genes had high connectivity with other photoperiod-sensitive DEGs. The expression levels of hub genes were verified by qRT-PCR analysis. CONCLUSION: An increase in light duration promotes earlier flowering of C. oleifera. Flavonoid biosynthesis, amino sugar and nucleotide sugar metabolism, and circadian rhythm pathways may function in the photoperiodic flowering pathway of C. oleifera. We also identified eight hub genes that may play a role in this pathway. Ultimately, this work contributes to our understanding of the photoperiodic flowering pathway of C. oleifera and further informs molecular breeding programs on the plant's photoperiodic sensitivity.

A20 alleviated caspase-1-mediated pyroptosis and inflammation stimulated by Porphyromonas gingivalis lipopolysaccharide and nicotine through autophagy enhancement.

Periodontitis is the leading cause of tooth loss, and patients with smoking habits are at an increased risk of developing periodontitis. A20 (the tumor necrosis factor alpha-induced protein 3, TNFAIP3) is one of the key regulators of inflammation and cell death in numerous tissues. Emerging researches indicated A20 as a fundamental molecule in the periodontal tissue. This study was to evaluate the role of A20 against cell death and inflammation in periodontitis and to elucidate the underlying mechanisms. In our study, western blot, autophagy detection, and transmission electron microscopy showed that lipopolysaccharide from Porphyromonas gingivalis (Pg.LPS) and nicotine (NI) could enhance the activation of autophagy. Pg.LPS and NI induce the pyroptosis of human periodontal ligament cells (hPDLCs), as evidenced by the decrease of membrane integrity and the increase of NLRP3, GSDMD, GSDMD-N, caspase-1 activity, and the pro-inflammatory cytokines of IL-1ß, IL-6, TNF-α. Further researches were focused on that A20, an ubiquitin-editing enzyme, was linked to hPDLCs pyroptosis. Overexpression or silencing A20 could diminish or aggravate pyroptosis in hPDLCs by the modulation of autophagy. The above results demonstrated that A20 dictated the cross-talk between pyroptosis and autophagy. Overexpression of A20 enhanced autophagy to reduce pyroptosis, and thus alleviating inflammation, suggesting that A20 may be a potent target in the treatment of periodontitis.

Robust intervention for oxidative stress-induced injury in periodontitis via controllably released nanoparticles that regulate the ROS-PINK1-Parkin pathway.

Oxidative stress in periodontitis has emerged as one of the greatest barriers to periodontal tissue restoration. In this study, we synthesized controlled drug release nanoparticles (MitoQ@PssL NPs) by encasing mitoquinone (MitoQ; an autophagy enhancer) into tailor-made reactive oxygen species (ROS)-cleavable amphiphilic polymer nanoparticles (PssL NPs) to regulate the periodontitis microenvironment. Once exposed to reactive oxygen species, which were substantially overproduced under oxidative stress conditions, the ROS-cleavable PssL was disintegrated, promoting the release of the encapsulated MitoQ. The released mitoquinone efficiently induced mitophagy through the PINK1-Parkin pathway and successfully reduced oxidative stress by decreasing the amount of reactive oxygen species. With the gradual decrease in the reactive oxygen species level, which was insufficient to disintegrate PssL, the release of mitoquinone was reduced and eventually eliminated, which contributed to a redox homeostasis condition and facilitated the regeneration of periodontal tissue. MitoQ@PssL NPs have great potential in the treatment of periodontitis via microenvironment-controlled drug release, which will provide a new avenue for periodontal regeneration and diseases related to imbalanced redox metabolism.

Cerium oxide nanoparticles loaded nanofibrous membranes promote bone regeneration for periodontal tissue engineering.

Bone regeneration is a crucial part in the treatment of periodontal tissue regeneration, in which new attempts come out along with the development of nanomaterials. Herein, the effect of cerium oxide nanoparticles (CeO2 NPs) on the cell behavior and function of human periodontal ligament stem cells (hPDLSCs) was investigated. Results of CCK-8 and cell cycle tests demonstrated that CeO2 NPs not only had good biocompatibility, but also promoted cell proliferation. Furthermore, the levels of alkaline phosphatase activity, mineralized nodule formation and expressions of osteogenic genes and proteins demonstrated CeO2 NPs could promote osteogenesis differentiation of hPDLSCs. Then we chose electrospinning to fabricate fibrous membranes containing CeO2 NPs. We showed that the composite membranes improved mechanical properties as well as realized release of CeO2 NPs. We then applied the composite membranes to in vivo study in rat cranial defect models. Micro-CT and histopathological evaluations revealed that nanofibrous membranes with CeO2 NPs further accelerated new bone formation. Those exciting results demonstrated that CeO2 NPs and porous membrane contributed to osteogenic ability, and CeO2 NPs contained electrospun membrane may be a promising candidate material for periodontal bone regeneration.

MOF-derived CoNi,CoO,NiO@N-C bifunctional oxygen electrocatalysts for liquid and all-solid-state Zn-air batteries.

Metal-organic framework (MOF)-derived carbon composites with embedded metal alloy/metal oxides have attracted much attention due to their low-cost and excellent electrochemical reactivity. However, the drawback of this concept is the severe carbon evaporation during their synthesis, resulting in a reduction of active sites and catalytic durability. To solve this problem, this study proposes the possibility of using Ketjen black (KB) to replenish the carbon content. Impressively, MOF-derived bimetal and oxide N-doped porous carbon (CoNi-CoO-NiO@NC-800) exhibits extremely high catalytic activity with an oxygen reduction reaction (half-wave potential: 0.83 V) and oxygen evolution reaction (overpotential: 352 mV @ 10 mA cm-2) potential gap of 0.75 V due to the virtue of the hierarchically porous structure and sufficient active sites. By combining theoretical studies, a strong synergetic coupling of the CoNi dual metal is proposed in decreasing the overall reaction barriers and promoting the reversible oxygen reactions. Moreover, the assembled liquid- and all-solid-state Zn-air batteries (ZABs) with the bifunctional catalyst as the air cathode demonstrate superior discharging (223 mW cm-2 at 310 mA cm-2) and charging-discharging performance and long lifetime (450 cycles, 75 h). This work will provide guidance for the rational design of metal/carbon hybrid catalysts and cut-price reproducible energy systems.

Molecular engineering in a family of pillared-layered metal-organic frameworks for tuning gas adsorption behavior.

In this work, inspired by a water-assisted three-dimensional supramolecular structure 1, we use a mixed-ligand strategy to form a 3D pillared-layered matrix by the introduction of linear ligands to compete against the water molecules. The resulting analogue microporous MOFs of 2-H, 2-F and 2-N, decorated with different functional groups, similarly show the CO2 uptake. Thanks to the negligible N2 adsorption capacity, enhanced selective adsorption towards CO2 is achieved in compound 2-N. That is, we present here an alternative plan for the high CO2 selective adsorption performance. In addition, the structure stability and moderate affinity for CO2 of these microporous MOFs endow them with excellent reusability.

MgO Nanoparticles-Incorporated PCL/Gelatin-Derived Coaxial Electrospinning Nanocellulose Membranes for Periodontal Tissue Regeneration.

Electrospinning technique has attracted considerable attention in fabrication of cellulose nanofibrils or nanocellulose membranes, in which polycaprolactone (PCL) could be used as a promising precursor to prepare various cellulose nanofibril membranes for periodontal tissue regeneration. Conventional bio-membranes and cellulose films used in guided tissue regeneration (GTR) can prevent the downgrowth of epithelial cells, fibroblasts, and connective tissue in the area of tooth root but have limitations related to osteogenic and antimicrobial properties. Cellulose nanofibrils can be used as an ideal drug delivery material to encapsulate and carry some drugs. In this study, magnesium oxide (MgO) nanoparticles-incorporated PCL/gelatin core-shell nanocellulose periodontal membranes were fabricated using coaxial electrospinning technique, which was termed as Coaxial-MgO. The membranes using single-nozzle electrospinning technique, namely Blending-MgO and Blending-Blank, were used as control. The morphology and physicochemical property of these nanocellulose membranes were characterized by scanning electron microscopy (SEM), energy-dispersive spectrum of X-ray (EDS), transmission electron microscopy (TEM), contact angle, and thermogravimetric analysis (TGA). The results showed that the incorporation of MgO nanoparticles barely affected the morphology and mechanical property of nanocellulose membranes. Coaxial-MgO with core-shell fiber structure had better hydrophilic property and sustainable release of magnesium ion (Mg2+). CCK-8 cell proliferation and EdU staining demonstrated that Coaxial-MgO membranes showed better human periodontal ligament stem cells (hPDLSCs) proliferation rates compared with the other group due to its gelatin shell with great biocompatibility and hydrophilicity. SEM and immunofluorescence assay results illustrated that the Coaxial-MgO scaffold significantly enhanced hPDLSCs adhesion. In vitro osteogenic and antibacterial properties showed that Coaxial-MgO membrane enhanced alkaline phosphatase (ALP) activity, formation of mineralized nodules, osteogenic-related genes [ALP, collagen type 1 (COL1), runt-related transcription factor 2 (Runx2)], and high antibacterial properties toward Escherichia coli (E. coli) and Actinobacillus actinomycetemcomitans (A. a) when compared with controls. Our findings suggested that MgO nanoparticles-incorporated coaxial electrospinning PCL-derived nanocellulose periodontal membranes might have great prospects for periodontal tissue regeneration.

Biodegradable engineered fiber scaffolds fabricated by electrospinning for periodontal tissue regeneration.

Considering the specificity of periodontium and the unique advantages of electrospinning, this technology has been used to fabricate biodegradable tissue engineering materials for functional periodontal regeneration. For better biomedical quality, a continuous technological progress of electrospinning has been performed. Based on property of materials (natural, synthetic or composites) and additive novel methods (drug loading, surface modification, structure adjustment or 3 D technique), various novel membranes and scaffolds that could not only relief inflammation but also influence the biological behaviors of cells have been fabricated to achieve more effective periodontal regeneration. This review provides an overview of the usage of electrospinning materials in treatments of periodontitis, in order to get to know the existing research situation and find treatment breakthroughs of the periodontal diseases.

An intrinsic mechanism for coordinated production of the contact-dependent and contact-independent weapon systems in a soil bacterium.

Soil bacteria possess multiple weapons to fend off microbial competitors. Currently, we poorly understand the factors guiding bacterial decisions about weapon systems deployment. In this study, we investigated how such decisions are made by the soil bacterium Lysobacter enzymogenes, used in antifungal plant protection. We found that weapons production is guided by environmental cues. In rich media, which likely mimic environments crowded with other microbes, L. enzymogenes produces a contact-dependent weapon, type six secretion system (T6SS). In nutrient-poor media, likely dominated by filamentous oomycetes and fungi, L. enzymogenes synthesizes and secretes a heat-stable antifungal factor (HSAF), a contact-independent weapon. Surprisingly, the T6SS inner tube protein Hcp is accumulated intracellularly even in nutrient-poor media, when the T6SS is not assembled. We found that Hcp interacts with the transcription factor Clp required for activating HSAF biosynthesis operon expression. Hcp protects Clp from binding to c-di-GMP, an intracellular second messenger inhibiting DNA binding. The increased concentration of c-di-GMP-free Clp thus leads to higher gene expression and HSAF production. Therefore, when the contact-dependent weapon, T6SS, is not in use, accumulation of one of its structural components, Hcp, serves as a signal to enhance production of the contact-independent weapon, HSAF. The uncovered environment-dependent and auto-regulatory mechanisms shed light on the processes governing deployment of various weapon systems in environmental bacteria.

Knockout of Diguanylate Cyclase Genes in Lysobacter enzymogenes to Improve Production of Antifungal Factor and Increase Its Application in Seed Coating.

Heat-stable antifungal factor (HSAF) is a broad-spectrum antifungal antibiotic produced by the biological control agent, Lysobacter enzymogenes. In our earlier works, we have applied HSAF to effectively control wheat and pear fungal disease. However, a major bottleneck in its practical application is the low HSAF production level; therefore, boosting its production is essential for its wide application. In the past, we find that c-di-GMP, a universal bacterial second messenger, is inhibitory to HSAF production. In this work, we further identified eight active diguanylate cyclases (DGCs) responsible for c-di-GMP synthesis in Lysobacter enzymogenes via both bioinformatics and genetic analyses. We generated a strain lacking seven active DGC genes and found that this DGC-modified strain, OH11LC, produced a higher HSAF amount in a c-di-GMP concentration-dependent manner. Subsequently, by employing OH11LC as the host fermentation strain, we could even produce a much higher HSAF amount (> 200-fold). After improving the HSAF production, we further developed a technique of seed coating method with HSAF, which turned out to be effective in fighting against the maize seed-borne filamentous pathogen, Pythium gramineacola. Overall, via combining strain modification and fermentation optimization, we demonstrated a good example of translating fundamental knowledge of bacterial c-di-GMP signaling into biological control application in which we relieved the inhibitory effect of c-di-GMP on HSAF biosynthesis by deleting a bunch of potentially active L. enzymogenes DGC genes to improve HSAF yield and to expand its usage in antifungal seed coating.

A20 inhibits osteoclastogenesis via TRAF6-dependent autophagy in human periodontal ligament cells under hypoxia.

OBJECTIVES: A20 exerts an anti-osteoclastogenic effect through the inhibition of NF-κB signalling in periodontitis. It also regulates autophagy via ubiquitin modification. This study was aimed at exploring the relationship between A20 and autophagy in anti-osteoclastogenesis in human periodontal ligament cells (hPDLCs) under hypoxia. MATERIALS AND METHODS: Real-time PCR and Western blot were used to detect relative mRNA and protein levels. The formation of autophagosomes was measured by TEM. Osteoclastic differentiation was assessed by TRAP staining and hydroxyapatite resorption assay. The interactions between different proteins were observed by co-IP. RESULTS: Cells cultured under 2% O2 exhibited decreased A20 expression and increased RANKL/OPG (R/O) ratio. There was a negative correlation between A20 and TRAF6, and similar results were found with autophagic flux. A20 delayed the increase in R/O ratio under hypoxia. Autophagy in hPDLCs and osteoclast differentiation and hydroxyapatite resorption areas in mouse bone marrow mononuclear cells (BMMCs) were inhibited by A20. Moreover, inhibition of autophagy using 3-MA resulted in increased expression of A20 and decreased number and function of osteoclasts. In addition, A20 inhibited polyubiquitination at K63 and enhanced that at K48 in TRAF6 to suppress autophagy under hypoxic conditions. CONCLUSIONS: A20 inhibits osteoclastogenesis via inhibition of TRAF6-dependent autophagy in hPDLCs under hypoxia. These findings suggest that A20 may be a key gene target during bone loss in periodontitis via TRAF6-mediated inhibition of autophagy.

Fluorescent labelling in living dental pulp stem cells by graphene oxide quantum dots.

Cellular labelling is possible to offer significant information after transplantation for the purpose of determining stem cell therapy's efficacy. According to the research, it has been reported that graphene oxide quantum dots (GOQDs) are a kind of healthy biological labelling agent for stem cells which show little cytotoxicity. GOQDs' interactions have been examined on the dental pulp stem cells (hDPSCs) of human beings for the purpose of investigating GOQD's biocompatibility and uptake and explored GOQDs' effects on hDPSCs' metabolic activity and the proliferation. According to the outcomes, GDQDs have been accepted by hDPSCs in a time-dependent and concentration-dependent behaviour. Moreover, no important changes have been discovered within hDOPSCs' proliferation, viability as well as metabolic activity after treatment with GOQDs. Therefore, such resources have shown that GOQDs can be multifunctional agents for cell therapy, drug delivery as well as cell imaging and also as outstanding candidates for labelling stem cells.

Ternary-Responsive Drug Delivery with Activatable Dual Mode Contrast-Enhanced in Vivo Imaging.

Designing a smart nanotheranostic system has recently attracted tremendous attention and is highly desirable for realizing targeted cancer therapy and early diagnosis. Herein we report the fabrication of smart nanotheranostic system using multiresponsive gatekeeping protocol of mesoporous silica nanoparticles (MSN). Acid, oxidative stress and redox sensitive manganese oxide (MnO x) coated superparamagnetic iron oxide nanoparticle (SPION) were employed as nanolids to regulate the camptothecin drug release from the channels of mesoporous silica and achieve responsive dual-mode MRI contrast. The nonvehicle showed high magnetization and T2 contrast in magnetic resonance imaging (MRI) due to the significant density of SPION onto the surface of MSN, and at the same time the MnO x shell degradation release Mn2+ which enhanced the T1MRI visualization. The efficacy of responsive drug delivery system was investigated on pancreatic cancer cells and tumor-bearing mice, and results reinforced that MnO x-SPION@MSN@CPT nonvehicle is efficacious against cancer cells. We envision that our unique and multiresponsive nanoplatform may find applications in effective delivering of imaging and therapeutic agents to wide range of diseases besides cancer.