MY-1-Loaded Nano-Hydroxyapatite Accelerated Bone Regeneration by Increasing Type III Collagen Deposition in Early-Stage ECM via a Hsp47-Dependent Mechanism.

The extracellular matrix (ECM) plays a crucial part in regulating stem cell function through its distinctive mechanical and chemical effect. Therefore, it is worth studying how to activate the driving force of osteoblast cells by dynamic changing of ECM and accelerate the bone regeneration. In this research, a novel peptide MY-1 is designed and synthesized. To achieve its sustained releasing, the nano-hydroxyapatite (nHA) is chosen as the carrier of MY-1 by mixed adsorption. The results reveal that the sustainable releasing of MY-1 regulates the synthesis and secretion of ECM from rat bone marrow mesenchymal stem cells (rBMSCs), which promotes the cell migration and osteogenic differentiation in the early stage of bone regeneration. Further analyses demonstrate that MY-1 increases the expression and nuclear translocation of ß-catenin, and then upregulates the level of heat shock protein 47 (Hsp47), thereby accelerating the synthesis and secretion of type III collagen (Col III) at the early stage. Finally, the promoted rapid transformation of Col III to Col I at late stage benefits the bone regeneration. Hence, this study can provide a theoretical basis for the local application of MY-1 in bone regeneration.

Periodontitis as a promoting factor of T2D: current evidence and mechanisms / 国际口腔科学杂志·英文版

Periodontitis is an infectious disease caused by an imbalance between the local microbiota and host immune response. Epidemiologically, periodontitis is closely related to the occurrence, development, and poor prognosis of T2D and is recognized as a potential risk factor for T2D. In recent years, increasing attention has been given to the role of the virulence factors produced by disorders of the subgingival microbiota in the pathological mechanism of T2D, including islet β-cell dysfunction and insulin resistance (IR). However, the related mechanisms have not been well summarized. This review highlights periodontitis-derived virulence factors, reviews how these stimuli directly or indirectly regulate islet β-cell dysfunction. The mechanisms by which IR is induced in insulin-targeting tissues (the liver, visceral adipose tissue, and skeletal muscle) are explained, clarifying the influence of periodontitis on the occurrence and development of T2D. In addition, the positive effects of periodontal therapy on T2D are overviewed. Finally, the limitations and prospects of the current research are discussed. In summary, periodontitis is worthy of attention as a promoting factor of T2D. Understanding on the effect of disseminated periodontitis-derived virulence factors on the T2D-related tissues and cells may provide new treatment options for reducing the risk of T2D associated with periodontitis.

Graphene oxide disrupted mitochondrial homeostasis through inducing intracellular redox deviation and autophagy-lysosomal network dysfunction in SH-SY5Y cells.

Graphene oxide (GO) nanomaterials have significant advantages for drug delivery and electrode materials in neural science, however, their exposure risks to the central nervous system (CNS) and toxicity concerns are also increased. The current studies of GO-induced neurotoxicity remain still ambiguous, let alone the mechanism of how complicated GO chemistry affects its biological behavior with neural cells. In this study, we characterized the commercially available GO in detail and investigated its biological adverse effects using cultured SH-SY5Y cells. We found that ultrasonic processing in medium changed the oxidation status and surface reactivity on the planar surface of GO due to its hydration activity, causing lipid peroxidation and cell membrane damage. Subsequently, ROS-disrupted mitochondrial homeostasis, resulting from the activation of NOX2 signaling, was observed following GO internalization. The autophagy-lysosomal network was initiated as a defensive reaction to obliterate oxidative damaged mitochondria and foreign nanomaterials, which was ineffective due to reduced lysosomal degradation capacity. These sequential cellular responses exacerbated mitochondrial stress, leading to apoptotic cell death. These data highlight the importance of the structure-related activity of GO on its biological properties and provide an in-depth understanding of how GO-derived cellular redox signaling induces mitochondrion-related cascades that modulate cell functionality and survival.

The mTOR/ULK1 signaling pathway mediates the autophagy-promoting and osteogenic effects of dicalcium silicate nanoparticles.

A novel bioactive inorganic material containing silicon, calcium and oxygen, calcium silicate (Ca2SiO4, C2S) with a CaO-SiO2 ingredient, has been identified as a potential candidate for artificial bone. Autophagy has an essential function in adult tissue homoeostasis and tumorigenesis. However, little is known about whether silicate nanoparticles (C2S NPs) promote osteoblastic differentiation by inducing autophagy. Here we investigated the effects of C2S NPs on bone marrow mesenchymal stem cell differentiation (BMSCs) in osteoblasts. Furthermore, we identified the osteogenic gene and protein expression in BMSCs treated with C2S NPs. We found that autophagy is important for the ability of C2S NPs to induce osteoblastic differentiation of BMSCs. Our results showed that treatment with C2S NPs upregulated the expression of BMP2, UNX2, and OSX in BMSCs, and significantly promoted the expression of LC3 and Beclin, while P62 (an autophagy substrate) was downregulated. C2S NP treatment could also enhance Alizarin red S dye (ARS), although alkaline phosphatase (ALP) activity was not significantly changed. However, all these effects could be partially reversed by 3-MA. We then detected potential signaling pathways involved in this biological effect and found that C2S NPs could activate autophagy by suppressing mTOR and facilitating ULK1 expression. Autophagy further activated ß-catenin expression and promoted osteogenic differentiation. In conclusion, C2S NPs promote bone formation and osteogenic differentiation in BMSCs by activating autophagy. They achieve this effect by activating mTOR/ULK1, inducing autophagy, and subsequently triggering the WNT/ß-catenin pathway to boost the differentiation and biomineralization of osteoblasts.

Toxicology data of graphene-family nanomaterials: an update.

Due to its unique physical structure and chemical properties, graphene family nanomaterials (GFNs) and derived commodities have been widely used in commercial products, particularly biomedical applications, which has significantly increased the risk of human exposure. There exists significant evidence that GFNs are accumulated in a number of tissues and organs through different exposure pathways, and further cause toxicity manifested as lesions or functional impairment. Moreover, GFNs can be internalized by varing cell types and induce cytoskeletal disorders, organelle dysfunction, and interact directly with biological macromolecules such as DNA, mRNA and proteins, ultimately resulting in greater rates of cell apoptosis, necrosis and autophagic cell death. The toxicological effect of GFN is closely related to its lateral size, surface structure, functionalization, and propensity to adsorb proteins. Using major data published over the past four years, this review presents and summarizes state of current understanding of GFN toxicology and identifies current deficiencies and challenges. This review aims to help improve evaluation of the biocompatibility of GFNs and provides theoretical guidance for their safe application.

Nanoscaffolds in promoting regeneration of the peripheral nervous system.

The ability to surgically repair peripheral nerve injuries is urgently needed. However, traditional tissue engineering techniques, such as autologous nerve transplantation, have some limitations. Therefore, tissue engineered autologous nerve grafts have become a suitable choice for nerve repair. Novel tissue engineering techniques derived from nanostructured conduits have been shown to be superior to other successful functional neurological structures with different scaffolds in terms of providing the required structures and properties. Additionally, different biomaterials and growth factors have been added to nerve scaffolds to produce unique biological effects that promote nerve regeneration and functional recovery. This review summarizes the application of different nanoscaffolds in peripheral nerve repair and further analyzes how the nanoscaffolds promote peripheral nerve regeneration.

Central neurotoxicity induced by the instillation of ZnO and TiO2 nanoparticles through the taste nerve pathway.

AIM: To explore whether nanoparticles (NPs) can be transported into the CNS via the taste nerve pathway. MATERIALS & METHODS: ZnO and TiO2 NPs were tongue-instilled to male Wistar rats. Toxicity was assessed by Zn/Ti biodistribution, histopathological examination, oxidative stress assay, quantitative reverse-transcriptase PCR analysis, learning and memory capabilities. RESULTS: ZnO NPs and TiO2 NPs significantly deposited in the nerves and brain, respectively. The histopathological examination indicated a slight injury in the cerebral cortex and hippocampus. Ultrastructural changes and an imbalanced oxidative stress were observed. The Morris water maze results showed that the learning and memory of rats were impaired. CONCLUSION: NPs can enter the CNS via the taste nerve translocation pathway and induce a certain adverse effect.

Prenatal exposure to nanosized zinc oxide in rats: neurotoxicity and postnatal impaired learning and memory ability.

AIM: To examine the neurotoxicity of prenatal exposure to ZnO nanoparticles on rat offspring. MATERIALS & METHODS: Pregnant Sprague-Dawley rats were exposed to ZnO nanoparticles (NPs) by gavage. Toxicity was assessed including zinc biodistribution, cerebral histopathology, antioxidant status and learning and memory capability. RESULTS: A significantly elevated concentration of zinc was detected in offspring brains. Transmission electron microscope observations showed abnormal neuron ultrastructures. Histopathologic changes such as decreased proliferation and higher apoptotic death were observed. An obvious imbalanced antioxidant status occurred in brains. Adult experimental offspring exhibited impaired learning and memory behavior in the Morris water maze test compared with control groups. CONCLUSION: These adverse effects on offspring brain may cause impaired learning and memory capabilities in adulthood, particularly in female rats.

Ion-shedding zinc oxide nanoparticles induce microglial BV2 cell proliferation via the ERK and Akt signaling pathways.

Given the wide application of zinc oxide nanoparticles (ZnO NPs), the health hazards of these particles have attracted extensive worldwide attention. Many more studies on the biological interactions of ZnO NPs have been performed in recent years. In this study, we focused on the biological effects on BV2 microglial cells induced by ZnO NPs at non- or sub-toxic concentrations. We found that ZnO NPs at a concentration of 5 µg/ml could significantly activate cell proliferation, while ZnO NPs at other concentrations did not. We also found that ZnO NPs induced microglial cell activation in a time-dependent manner. Moreover, a potent increase in the ratio of cells in S phase at all ZnO NPs concentrations was observed in a cell cycle analysis. Using inductively coupled plasma mass spectrometry (ICP-MS) and immunocytochemistry techniques, we demonstrated that ZnO dissolution could occur in the culture medium and in the lysosomes of BV2 cells. ZnO NPs significantly induced the phosphorylation of ERK and Akt, which might be involved in promoting cell proliferation. In conclusion, our results demonstrated that ZnO NPs induced BV2 microglial cell proliferation probably via the release of zinc ions from ZnO, which could then activate the ERK and Akt signaling pathways.

The ethanol extract of Osmanthus fragrans attenuates Porphyromonas gingivalis lipopolysaccharide-stimulated inflammatory effect through the nuclear factor erythroid 2-related factor-mediated antioxidant signalling pathway.

BACKGROUND: In the present study, we explored the effect of the ethanol extract of Osmanthus fragrans (EOF) on the growth and collagenase activity of Porphyromonas gingivalis (P. gingivalis). We also investigated the capacity of EOF to attenuate P. gingivalis lipopolysaccharide (LPS)-induced inflammatory responses and the possible signalling pathway. METHODS: EOF was obtained by soaking the O. fragrans powder in the ethanol and concentrating the extracts under reduced pressure. Microplate dilution assays were used to determine the effect of EOF on P. gingivalis growth. Collagenase inhibition was detected using fluorometric and colorimetric assays. The effects of EOF on the production of the cytokines interleukin-6 (IL-6) and IL-8 were assessed using enzyme-linked immunosorbent assays (ELISAs). The oxidative stress biomarkers were assayed using commercial kits. The effects of EOF on the expression of cytoprotective enzymes and nucleoprotein nuclear factor erythroid 2-related factor (Nrf2) were tested by Western blot analysis. RESULTS: EOF significantly inhibited the growth of P. gingivalis, especially in the iron-limited culture medium. The inhibitory effect of EOF on P. gingivalis collagenase activity was time- and concentration-dependent. The P. gingivalis LPS-stimulated production of IL-6 and IL-8 was attenuated by EOF. LPS significantly induced the production of nitric oxide (NO) and malondialdehyde (MDA), and decreased the expression of superoxide dismutase (SOD) while pretreatment with EOF alleviated these effects. The presence of EOF markedly upregulated the expression levels of the cytoprotective enzymes and nucleoprotein Nrf2. CONCLUSION: This study suggests that the potent Nrf2 activation capacity of O. fragrans may be useful in the adjunctive treatment of periodontal disease.

Potential proinflammatory and osteogenic effects of dicalcium silicate particles in vitro.

BACKGROUND: Due to their biocompatibility and bioactivity, dicalcium silicate (C2S) and hydroxyapatite (HA) are used as coating materials for prosthetic orthopedic and dental implants or as bone substitute materials to fill bone defects. However, prostheses and bone substitutes can release particles that trigger an immune response in the recipient. The immunological effects of C2S particles have not yet been studied. OBJECTIVE: The aim of this study was to determine the cytotoxic effects of C2S particles on primary human monocytes, a human monocyte cell line (THP-1) and an osteoblast-like cell line (MG-63). The proinflammatory effects of C2S particles on THP-1 were also detected. Moreover, the osteogenic effects of C2S and HA on MG-63 cells were investigated. METHODS: Characterization of C2S and HA was performed using scanning electron microscopy (SEM), energy dispersive analysis (EDS), X-ray diffraction (XRD), Brunner-Emmett-Teller (BET) measurements and laser diffraction. The cytotoxic effect of C2S on primary human monocytes as well as THP-1 and MG-63 cells was measured using Trypan blue assays, Cell Counting Kit-8 (CCK-8) assays and flow cytometry to detect apoptosis. THP-1 human monocytes with or without lipopolysaccharide (LPS) stimulation were exposed to C2S and HA for 6 and 24h. Thereafter, the mRNA expression and protein concentrations of MMP-2, MMP-9, TIMP-2, TIMP-1 and TNF-α were evaluated using real-time PCR and ELISA, respectively. RANKL and OPG mRNA expression levels in MG-63 cells were examined using real-time PCR. RESULTS: No significant cytotoxicity was recorded when cells were directly cultured with C2S/HA particles. After THP-1 cells were cultured with C2S/HA for 24h, MMP-2, MMP-9 and TNF-α expression increased, whereas TIMP-2 and TIMP-1 expression decreased. Compared with HA, C2S slightly increased MMP-9 expression and slightly decreased TIMP-1 expression. The MMP: TIMP ratio increased in the C2S and HA groups; however, HA significantly increased the MMP-9: TIMP-1 ratio compared with C2S. Compared with HA, C2S caused less TNF-α production. C2S/HA did not modify the expression of proinflammatory mediators in LPS-stimulated cells. Furthermore, C2S/HA significantly increased OPG expression and slightly increased RANKL expression in MG-63 cells. C2S and HA decreased the RANKL: OPG ratio. CONCLUSION: Our in vitro data suggest that C2S is relatively safe when directly cultured with cells. In addition, C2S may exert proinflammatory effects; however, compared with HA, C2S had fewer proinflammatory effects on THP-1. C2S and HA did not alter the LPS-induced production of proinflammatory mediators and had similar osteogenic effects on MG-63 cells.

Load-bearing capacity and the recommended thickness of dental monolithic zirconia single crowns.

PURPOSE: The aim of this study was to evaluate the load bearing capacity and a reasonable thicknesss of dental monolithic zirconia crowns. MATERIALS AND METHODS: Polymethyl methacrylate (PMMA) abutment tooth specimens were made by CAD/CAM technic. Monolithic zirconia crowns (MZC), monolithic lithium disilicate crowns (MLC), layered zirconia crowns (LZC) and metal ceramic crowns(MCC), of which the occlusal thickness was 1.5mm were thereafter fabricated and cemented on the abutment tooth specimens. MCC with occlusal thicknesses of 0.6mm, 0.8mm, 1.00mm, 1.2mm were also made. All specimens underwent load-to-fracture test. Weibull parameters (σ0) and (m) were calculated. Fracture modes were also evaluated. RESULTS: The mean fracture load was 1863.16±116.81 for MLC, 2284.77±355.60 for MCC, 2308.0±510.94 for LZC, 4109.93±610.18 for MZC (1.5mm), 3068.31±233.88 for MZC (1.2mm), 2429.88±315.03 for MZC (1.0mm), 1814.60±68.21 for MZC (0.8mm) and 1308.38±111.38 for MZC (0.6mm). The fracture load of MZC was significantly higher than MCC, LZC and MLC (P<0.05). The fracture loads for MCC with different thickness were significantly different (P<0.05). Similar trend was observed for the characteristic strength (σ0) and Weibull modulus (m). For MZC and MLC, the fracture mode was catastrophic failure. The predominant fracture mode for LZC was catastrophic fracture. The fracture loads of MZC(1.0mm) and MCC were not statistically different (P>0.05). CONCLUSIONS: Monolithic zirconia crowns exhibit higher fracture loads than monolithic lithium disilicate crowns, layered zirconia crowns and metal ceramic crowns. The fracture resistance of monolithic zirconia crowns with a thickness of 1.0mm can be equal to metal ceramic crowns. Doubling the monolithic zirconia core from 0.6mm to 1.5mm increases the fracture resistance of this restorative system threefold.

The finite element analysis of deformation of maxillary sinus mucosa when elevated by three lift materials / 实用口腔医学杂志

Objective:To compare the maxillary sinus mucosa's stress distribution when elevated by three lift materials.Methods:Three Finite element models of maxillary sinus mucosa with 0.3 mm thickness elevated by implant,grafting autogenous cancellous bone and hydroxyapatite respectively were established in the specific units.ANSYS finite element analysis software was used to evaluate maxillary sinus mucosa deformation by the simulated closed sinus lift surgery.Differences of Von Mises stress values of mucosa surface were calculated when maxillary sinus mucosa lift height was increased from 1 mm to 5 mm according to the a large deformation theory. Results:The Von Mises stress values on membrane surface elevated by implant,grafting autogenous cancellous bone and hydroxyapa-tite bone substitute materials showed no difference within 5 mm elevation.Conclusion:Closed maxillary sinus floor lifting operation with implant elevating the maxillary sinus membrane directly is a simple and minimally invasive way for sinus floor elevation.

Finite element analysis on the deformation of maxillary sinus mucosa after closed maxillary sinus augmentation / 中国组织工程研究

BACKGROUND:How to avoid iatrogenic maxil ary sinus mucosal perforation after closed maxil ary sinus augmentation. OBJECTIVE:To compare the influence of maxil ary sinus mucosa at different thicknesses on the mucosal perforation in closed maxil ary sinus augmentation operation by using finite element analysis. METHODS:Three finite element models of maxil ary sinus mucosa at different thicknesses of 0.3 mm, 0.5 mm, 0.8 mm respectively and implant with 4.2 mm diameter were established in the SHELL63 units. ANSYS finite element analysis software was used to evaluate maxil ary sinus mucosal deformation by the simulated closed maxil ary sinus augmentation surgery. Differences of Von Mises maximum stress values of mucosa surface were calculated according to the non-linear large-deformation theory. RESULTS AND CONCLUSION:When maxil ary sinus mucosa height was increased from 1 mm to 5 mm, the large deformation was observed in the center of mucosa center. The maximum stress curve slope was shifted mild between 1-4 mm deformation, while shifted abruptly after 4 mm. There was no difference in the value of Von Mises maximum stress values between three maxil ary sinus mucosa at 0.3 mm, 0.5 mm, 0.8 mm thickness, when the lift height was increased from 1 mm to 5 mm (P>0.05). Maxil ary sinus mucosa are faced with a higher risk of mucosal perforation and elastic elongation when maxil ary sinus height is increased more than 4 mm. Maxil ary sinus mucosa at 0.3-0.8 mm thickness are faced the similar risk of mucosal perforation in closed maxil ary sinus augmentation operation within 5 mm. While more considerations should be paid on patients with less than 0.3 mm maxil ary sinus mucosa thickness.

Evaluation on teaching effect of interactive teaching in prosthodontics course / 中华医学教育探索杂志

Objective To research the efficiency of interactive teaching combined with group discussion in prosthodontics course. Methods Totally 40 stomatology students of 2009 grade were divid-ed into 2 groups by stratified random sampling , 6 males and 14 females in each group. Students in con-trol group were taught by traditional teaching method while those in the test group were taught by interac-tive teaching method during prosthodontics course. Knowledge lectures and cases discussion in interactive teaching method were distributed as ratio of 3∶1 in class time , and network interactive teaching was car-ried out after class. Exam was taken after the course, which included single choices(80 questions, 80 points), true or false questions(20 questions, 20 points) and case analysis(5 questions, 50 points). Full marks of the exam was 150 points and exam time was 150min. Then questionnaire survey was carried out, which included the students' interest in learning and cognition of learning difficulty. Exam scores were statistically analyzed by two sample t-test(α=0.05) and the questionnaire survey results were statistically analyzed by Mann-Whitney U test(α=0.05). Results Average scores were(109.22±8.22) in control group and(126.28±8.72) in test group, with statistical differences(F=1.1254, P=0.000). There were statistical differences between control group and test group in studying interest(Z=-2.869, P=0.004) and difficulty(Z=-2.711, P=0.007). Conclusions Initiative, thinking capacity and scores can be enhance by interactive teaching method which is more efficiently than traditional teaching method.

Influence of background color on four veneered dental ceramic core material / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the influence of background color on veneered In-Ceram and Cercon dental ceramics including Vita In-Ceram Electroformed Alumina (AL2), Electroformed Zirconia (Z21), Cercon base color Zirconia and Cercon base Zirconia.</p><p><b>METHODS</b>The colorimetric values of all the materials on noble metal, Ni-Cr alloy, silver amalgam and resin background were measured with a spectrocolorimeter, and the color difference among the groups was calculated.</p><p><b>RESULTS</b>After veneered, the color difference of Z21 Electroformed Zirconia was more distinct against the background of silver amalgam than against the backgrounds of noble metal and resin, but the color differences of the 4 veneered dental ceramics against different backgrounds were unidentifiable by human eyes (δE<1.5).</p><p><b>CONCLUSION</b>After veneered, AL2 electroformed alumina, Z21 electroformed zirconia, Cercon base Zirconia and Cercon base color Zirconia are less influenced by the background color, and covering the background color is therefore not necessary.</p>

Research of stomatology teaching for international medical students / 中华医学教育探索杂志

A questionnaire survey was conducted among undergraduate international students to investigate the effects of stomatology teaching.The effects of stomatology teaching had been proved to be fair, while some shortcomings had also emerged. In further teaching adjustments have to be made to teaching plans and teachers' Enghsh abilities are expected to be improved.