A Metal-Polymer Hybrid Biomimetic System for use in the Chemodynamic-Enhanced Photothermal Therapy of Cancers.

This article reports the fabrication of a smart biomimetic enzyme system, which incorporates a pH-responsive chemodynamic therapy (CDT) combined with a photothermal (PTT) therapy approach in resolving the high recurrence rate of deadly cancers. The resulting enzyme system comprises copper sulfide (CuS) nanoparticle (NP) cores as Fenton-like catalysts, and a photothermal-active generation 5 poly(amidoamine) (G5) dendrimer as a template for the entrapment of Cu NPs and the compression of glucose oxidase (GOD). GOD is introduced to produce H2 O2 necessary in the sequential Fenton-like reaction, and this generates hydroxyl radicals that kill the cancerous cells. Polyethylene glycol is added to the system to improve biocompatibility. Mechanism study suggests that the constructed CuS/G5-GOD-based system has a better Fenton-like catalytic activity than a Fe3 O4 -GOD-based system. This allows the further inhibition on the residual tumors from recurrence and metastasis through CDT after being treated by PTT. The developed smart nanoscale biomimetic system shows high efficiency for breast cancer suppression from recurrence and metastasis by combining PTT with a pH-responsive CDT. It has the potential to resolve the essential issue of cancer recurrence after its initial clinic treatment.

Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome.

BACKGROUND: Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. METHODS: The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. RESULTS: Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. CONCLUSION: Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.

[Effects of Combined Stress of High Density Polyethylene Microplastics and Chlorimuron-ethyl on Soybean Growth and Rhizosphere Bacterial Community].

With the vigorous development of agriculture in China， plastic mulch film and pesticides are widely used in agricultural production. However， the accumulation of microplastics （formed by the degradation of plastic mulch film） and pesticides in soil has also caused many environmental problems. At present， the environmental biological effects of microplastics or pesticides have been reported， but there are few studies on the combined effects on crop growth and the rhizosphere soil bacterial community. Therefore， in this study， the high density polyethylene microplastics （HDPE， 500 mesh） were designed to be co-treated with sulfonylurea herbicide chlorimuron-ethyl to study their effects on soybean growth. In addition， the effects of the combined stress of HDPE and chlorimuron-ethyl on soybean rhizosphere soil bacterial community diversity， structure composition， microbial community network， and soil function were investigated using high-throughput sequencing technology， interaction network， and PICRUSt2 function analysis to clarify the combined toxicity of HDPE and chlorimuron-ethyl to soybean. The results showed that the half-life of chlorimuron-ethyl in soil was prolonged by the 1% HDPE treatment （from 11.5 d to 14.3 d）， and the combined stress of HDPE and chlorimuron-ethyl had more obvious inhibition effects on soybean growth than that of the single pollutant or control. The HiSeq 2 500 sequencing showed that the rhizosphere bacterial community of soybean was composed of 20 phyla and 312 genera under combined stress， the number of phyla and genera was significantly less than that of the control and single pollutant treatment， and the relative abundances of bacteria with potential biological control and plant growth-promoting characteristics （such as Nocardioides and Sphingomonas） were reduced. Alpha diversity analysis showed that the combined stress significantly reduced the richness and diversity of the soybean rhizosphere bacterial community， and Beta diversity analysis showed that the combined stress significantly changed the structure of the bacterial community. The dominant flora of the rhizosphere bacterial community were regulated， and the abundances of secondary functional layers such as amino acid metabolism， energy metabolism， and lipid metabolism were reduced under combined stress by the analysis of LEfSe and PICRUSt2. It was inferred from the network analysis that the combined stress of HDPE and chlorimuron-ethyl reduced the total number of connections and network density of soil bacteria， simplified the network structure， and changed the important flora species to maintain the stability of the network. The results above indicated that the combined stress of HDPE and chlorimuron-ethyl significantly affected the growth of soybean and changed the rhizosphere bacterial community structure， soil function， and network structure. Compared with that of the single pollutant treatment， the potential risk of combined stress was greater. The results of this study can provide guidance for evaluating the ecological risks of polyethylene microplastics and chlorimuron-ethyl and for the remediation of contaminated soil.

Can graphene oxide cause damage to eyesight?

As graphene becomes one of the most exciting candidates for multifunctional biomedical applications, contact between eyes and graphene-based materials is inevitable. On the other hand, eyes, as a special organ in the human body, have unique advantages to be used for testing new biomedical research and development, such as drug delivery. Intraocular biocompatible studies on graphene-related materials are thus essential. Here, we report our recent studies on intraocular biocompatibility and cytotoxicity of graphene oxide (GO) both in vitro and in vivo. The successful preparation of GO nanosheets was confirmed using atomic force microscopy, contact angle analyzer, Fourier transform infrared spectroscopy, and Raman spectroscopy. The influence of GO on human retinal pigment epithelium (RPE) cells in terms of the cell morphology, viability, membrane integrity, and apoptosis was investigated using various techniques, including optical micrography, cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, and apoptosis assay. The addition of GO had little influence on cell morphology, but the change was visible after long-time culturing. RPE cells showed higher than 60% cell viability by CCK-8 assay in GO solutions and less than 8% LDH release, although a small amount of apoptosis (1.5%) was observed. In vitro results suggested good biocompatibility of GO to RPE cells with slight adverse influence, on the cell viability and morphology in long-time periods, along with aggregation of GO. Thus, some further studies are needed to clarify the cytotoxicity mechanism of GO. GO intravitreally injected eyes showed few changes in eyeball appearance, intraocular pressure (IOP), eyesight, and histological photos. Our results suggested that GO did not cause any significant toxicity to the cell growth and proliferation. Intravitreal injection of GO into rabbits' eyes did not lead to much change in the eyeball appearance, IOP, electroretinogram, and histological examination.

The expression of inducible nitric oxide synthase in the gingiva of rats with periodontitis and diabetes mellitus.

OBJECTIVE: To ascertain the role of inducible nitric oxide synthase (iNOS) in the periodontitis response during diabetes. METHODS: Twenty-four male SD rats were randomly divided into four groups: control group (Control), diabetes mellitus group (D), diabetes mellitus plus periodontitis group (DP), and periodontitis group (P). Periodontitis and diabetes were established separately. Then the gingival tissue and alveolar bone were collected. A stereomicroscope was used to evaluate bone loss. The expression of iNOS, TNF-α, and NF-κB in the gingiva was detected by immunohistochemical staining, real-time PCR, and western blot analysis. RESULTS: Significant bone loss was observed in the DP and P groups and more extensive bone resorption was discovered in the DP group than in the P group (P < 0.05). The immunohistochemical staining analysis revealed enhanced expression of iNOS located in the gingiva of the three disease groups compared with the control group (P < 0.05). In particular, the level of iNOS was significantly higher in the DP group than in the P group (P < 0.05). This elevated trend of iNOS was further demonstrated by quantitative PCR and western blot analysis. Similarly, the mRNA and protein expression levels of NF-κB in the D, DP, and P groups were significantly higher than those of the control group, as was the level of TNF-α protein (P < 0.05). CONCLUSIONS: Our results proved diabetes exacerbated alveolar bone resorption in a periodontitis rat model. iNOS may be the inflammatory mediator in the course of periodontal injury promoted by diabetes.

Adsorption of chlorophenols on polyethylene terephthalate microplastics from aqueous environments: Kinetics, mechanisms and influencing factors.

Microplastics have received growing attention as carriers of organic pollutants in the water environment. To better understand the contribution of hydrophobic interaction, hydrogen-bonding interaction, π-π interaction and electrostatic interaction on the adsorption of hydrophilic compounds on microplastics and their adsorption behavior in natural waters, polyethylene terephthalate (PET, <150 µm) was used as an adsorbent and 4-chlorophenol (MCP), 2,4-dichlorophenol (DCP) and 2,4,6-trichlorophenol (TCP) were used as adsorbates. The results of batch adsorption experiments showed that chlorophenols (CPs) reached adsorption sites of PET through film diffusion and intra-particle diffusion. pH greatly affected the adsorption capacity. Hydrophobic interaction was the main adsorption mechanism of undissociated CPs on PET. Hydrogen-bonding interaction was also an adsorption mechanism between undissociated CPs and PET, and the contribution of hydrogen-bonding interaction to adsorption decreased with the increase of chlorine content. Meanwhile, the increase of chlorine content was favorable to the hydrophobic interaction between undissociated CPs and PET. However, higher chlorine content CPs with lower pKa values tended to dissociate at neutral pH condition and resulted in stronger electrostatic repulsion with PET. The increase of solution ionic strength and fulvic acid content negatively affected the adsorption of DCP and TCP on PET, but did not show significant impacts on MCP adsorption. Similarly, the adsorption capacity obtained using Taihu lake water and Bohai seawater as matrices was much lower than that using laboratory water for both DCP and TCP, while the adsorption coefficient (Kd) of MCP remained at approximately 10.6 L/kg to 11.4 L/kg in the three different solution matrices. The Kd values exhibited using natural water matrices consistently followed the order of DCP > MCP > TCP. This study provides insights into the fate of CPs in the presence of microplastics and suggests that the potential risks posed by CPs and microplastics to aqueous ecosystems merit further investigation.

[Experimental investigation of hepatic arterial embolism treatment with microsphere encapsulation of adenovirus with HSV-TK gene].

OBJECTIVE: To evaluate the suitability of the biodegradable microsphere encapsulation of adenovirus as a targeting vector for gene therapy of hepatocellular carcinoma. METHODS: Technique of homologous recombination in bacteria was applied to generate recombinant adenovirus with HSV-TK gene. After obtained the resulting recombinant adenovirus, the solution evaporation method was applied to encapsulate the recombinant adenovirus in poly (lactic/glycolic acid) (PLGA) copolymer. The Wistar rat implantation hepatocellular carcinoma model was set up by inserting the W256 tumor solid piece into Wistar rat's liver. Seven days after implantation on liver, the rats were injected through the proper hepatic artery. All of the rats were divided randomly into five groups: control group (Z1 group); normal saline group (Z2 group), AdEasy-GFP-TK group (Z3 group); placebo PLG microspheres group (Z4 group); PLG microspheres encapsulation of AdEasy-GFP-TK group (Z5 group). All of the proper hepatic arteries were ligated except the rats in Z1 group, following by injecting GCV intraperitoneously. The volume and the weight changes of tumor and the life time of the rats were measured. The in situ hybridization was performed to determinate the HSV-TK gene's transfection. RESULTS: The growth inhibition of tumor and the mean life length in Z5 group was superior to other groups. The expression of HSV-TK was observed in Z3 group and Z5 group by hybridization in situ. CONCLUSION: Genes for gene therapy could transfected into cells of hepatocellular carcinoma efficiently through the proper hepatic artery injection with recombinant adenovirus encapsulated in PLG microsphere. This could improve the effect of gene therapy remarkably.

PEGylation of lipophilic SN38 prodrug with DSPE-mPEG2000 versus cremophor EL: comparative study for intravenous chemotherapy.

The lipophilic prodrug of hydrophobic drugs with well-designed molecular structures can form stable pure prodrug nanoparticles (NPs), but rapid NPs aggregation in plasma greatly restricted their direct use for intravenous chemotherapy. To address this, DSPE-mPEG2000 and Cremophor EL are two of the most widely used lipophilic PEG derivatives to enhance their colloidal stability in plasma. However, their drug delivery performances have never been comparatively studied. Here, a redox-responsive lipophilic prodrug of SN38 was chosen as the model drug for such comparative investigations. We found that Cremophor EL/NPs having a small diameter (∼15 nm) and poor kinetic stability displayed an enhanced cell internalization, higher cytotoxicity and prolonged circulation time as compared with DSPE-mPEG2000/NPs. Most importantly, these superiorities further resulted in a much more potent antitumor activity in CT26 colorectal cancer xenograft, but the increased loss of body weight was also noted. These results suggested that Cremophor EL could be more advantageous than DSPE-mPEG2000 in terms of the improvement of antitumor activity, but the enhanced toxicity warranted further attention in the future study.

[Preparation of docetaxel-loaded pH-sensitive block copolymer micelles].

Basing on the synthesis of pH-sensitive amphiphilic block copolymer poly (2-ethyl-2-oxazoline)-poly (D, L-lactide)(PEOz-PDLLA), this paper presents the preparation of docetaxel-loaded pH-sensitive block copolymer micelles using film dispersion method. The critical micelle concentration (CMC) was measured by pyrene fluorescent probe technique. The entrapment efficiency and drug-loaded amount were determined by HPLC. The morphology, diameter and surface potential of the micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential analyzer, respectively. The in vitro release behavior of DTX from polymeric micelles was investigated using dialysis method. The results indicated that the CMC, drug-loaded amount and entrapment efficiency of the micelles was 1.0 x 10(-3) g x L(-1), 15.0% and 91.1%, respectively. The micelles had a narrow size distribution, with a mean diameter of 28.7 nm. The micelle was globular-shaped and its zeta potential was (1.19 +/- 0.12) mV. In pH 7.4 PBS, docetaxel was released in a sustained manner from the micelles; while in PBS at pH 5.0, drug was released more rapidly, which suggested the pH-sensitive drug release behavior of the PEOz-PDLLA micelles. According to all the studies above, it can be concluded that the PEOz-PDLLA block copolymer micelles may be applied as promising drug delivery system for hydrophobic anti-tumor drugs.

Hydroxyl-Functional Groups on Graphene Trigger the Targeted Delivery of Antitumor Drugs.

An efficient and targeted treatment for tumor cells is demonstrated. This targeting is based upon the strong affinity between hydroxyl-functional groups on graphene and acidic tumors. The hydroxylated graphene (GOH) with a unique 2D architecture further improve the targeting capacity of the system via an enhanced permeability and retention (EPR) process. Polyethylene glycol (PEG) was employed for better biocompatibility and the antitumor drug doxorubicin (DOX) was then incorporated. These additions created a biocompatible system with a superior pH-dependent drug release property. Its proficiency was due to its ability to pass through cell membranes via a process of endocytosis and exocytosis. The results from a Transwell co-culture system discovered that the PEG-GOH-DOX system had a large impact on tumor cell viability (less than 10% survived after treatment) and little influence on normal cells (more than 80% survived). An in vitro 3D tumor model study demonstrated that the size of the PEG-GOH-DOX treated tumor was 50% less than that of the pristine DOX treated tumor. In vivo data indicated that the PEG-GOH-DOX system was able to inhibit the size of tumors by a factor of 6.5 when compared to the untreated tumors.

Insulin-like growth factor-1 promotes the proliferation and odontoblastic differentiation of human dental pulp cells under high glucose conditions.

Insulin-like growth factor-1 (IGF-1) promotes human dental pulp stem cell proliferation and osteogenic differentiation. However, the effects of IGF-1 on the proliferation, apoptosis and odontoblastic differentiation (mineralization) of dental pulp cells (DPCs) under high glucose (GLU) conditions remain unclear. In this study, isolated primary human DPCs were treated with various concentrations of high GLU. Cell proliferation and apoptosis were determined by Cell Counting Kit-8 and Annexin V-FITC/PI assays, respectively. The cells were cultured in odontoblastic induction medium containing various concentrations of high GLU. Odontoblastic differentiation was determined by alkaline phosphatase (ALP) activity assay. Mineralization formation was evaluated by von Kossa staining. The expression levels of IGF family members were measured by western blot analysis and RT-qPCR during proliferation and differentiation. The cells were then exposed to 25 mM GLU and various concentrations of IGF-1. Cell proliferation, apoptosis, ALP activity, mineralization formation and the levels of mineralization-related proteins were then evaluated. Our results revealed that high GLU significantly inhibited cell proliferation and promoted cell apoptosis. GLU (25 and 50 mM) markedly reduced ALP activity and mineralization on days 7 and 14 after differentiation. The levels of IGF family members were markedly decreased by high GLU during proliferation and differentiation. However, IGF-1 significantly reversed the effects of high GLU on cell proliferation and apoptosis. Additionally, IGF-1 markedly restored the reduction of ALP activity and mineralization induced by high GLU. Our findings thus indicate that IGF-1 attenuates the high GLU-induced inhibition of DPC proliferation, differentiation and mineralization.

Sirtuin 1 regulates matrix metalloproteinase-13 expression induced by Porphyromonas endodontalis lipopolysaccharide via targeting nuclear factor-κB in osteoblasts.

Porphyromonas endodontalis lipopolysaccharide (P.e LPS) is an important initiating factor for periapical inflammation and bone destruction. Matrix metalloproteinase-13 (MMP-13) has been shown to participate in the formation and diffusion of periapical bone lesion in chronic apical periodontitis. Sirtuin 1 (SIRT1) is a key regulator of inflammation in mammalian cells which suppresses the release of inflammatory mediators. This study aimed to explore the role of SIRT1 in regulating MMP-13 expression induced by P.e LPS in osteoblasts. P.e LPS stimulated MMP-13 expression in MC3T3-E1 cells. Knockdown of SIRT1 reinforced the increase of MMP-13mRNA expression induced by P.e LPS. SIRT1 activator resveratrol significantly reduced the expression of MMP-13 and SIRT1 inhibitor EX-527 enhanced the expression of MMP-13. Moreover, SIRT1 activation with resveratrol inhibited acetylation of NF-κB p65 and NF-κB transcriptional activity, which were enhanced by P.e LPS. In addition, NF-κB p65 was involved in P.e LPS-induced MMP-13 expression via directly binding to the MMP-13 promoter. However, SIRT1 activation significantly interfered with this binding. These findings strongly suggest that P.e LPS induces MMP-13 expression in osteoblasts, and SIRT1 suppresses this expression of MMP-13 through targeting NF-κB p65. This provides new insights into understanding the actions of SIRT1 on anti-inflammatory and anti-bone resorption activity.

Aligned Nanofibers from Polypyrrole/Graphene as Electrodes for Regeneration of Optic Nerve via Electrical Stimulation.

The damage of optic nerve will cause permanent visual field loss and irreversible ocular diseases, such as glaucoma. The damage of optic nerve is mainly derived from the atrophy, apoptosis or death of retinal ganglion cells (RGCs). Though some progress has been achieved on electronic retinal implants that can electrically stimulate undamaged parts of RGCs or retina to transfer signals, stimulated self-repair/regeneration of RGCs has not been realized yet. The key challenge for development of electrically stimulated regeneration of RGCs is the selection of stimulation electrodes with a sufficient safe charge injection limit (Q(inj), i.e., electrochemical capacitance). Most traditional electrodes tend to have low Q(inj) values. Herein, we synthesized polypyrrole functionalized graphene (PPy-G) via a facile but efficient polymerization-enhanced ball milling method for the first time. This technique could not only efficiently introduce electron-acceptor nitrogen to enhance capacitance, but also remain a conductive platform-the π-π conjugated carbon plane for charge transportation. PPy-G based aligned nanofibers were subsequently fabricated for guided growth and electrical stimulation (ES) of RGCs. Significantly enhanced viability, neurite outgrowth and antiaging ability of RGCs were observed after ES, suggesting possibilities for regeneration of optic nerve via ES on the suitable nanoelectrodes.

Indocyanine green targeted micelles with improved stability for near-infrared image-guided photothermal tumor therapy.

AIM: Indocyanine green (ICG) is a promising near-infrared (NIR) dye for tumor imaging and photothermal therapy; however, the poor stability and lack of targeting limit its application. In this study, ICG was encapsulated into folate-conjugated poly(2-ethyl-2-oxazoline)-b-poly(ε-caprolactone) micelles to overcome these problems. MATERIALS & METHODS: ICG-loaded micelles were prepared by solvent evaporation method. Cell uptake and in vitro photothermal cytotoxicity were evaluated on KB cells. In vivo NIR imaging and photothermal therapy were conducted on KB tumor-bearing mice. RESULTS: ICG-loaded micelles with favorable sizes and stable NIR optical properties were successfully prepared. These micelles could target to KB tumors and enabled high-resolution NIR imaging. Moreover, they could effectively convert the absorbed NIR laser energy into heat, resulting in significant tumor damage and inhibition. CONCLUSION: This novel micellar system, integrating stable NIR properties, excellent tumor targeting and photothermal capability, showed great potential in tumor imaging and therapy.

Ocular biocompatibility evaluation of hydroxyl-functionalized graphene.

We have presented our recent efforts on genotoxicity and intraocular biocompatibility of hydroxylated graphene (G-OH) prepared by ball milling. We have previously demonstrated that the as-synthesized G-OH could be considered as an excellent alternative for graphene oxide which had been applied widely. Following our last report on G-OH, we carried out detailed studies on genotoxicity and in vivo biocompatibility of G-OH in this work. Less than 5% enhanced caspase-3 level was observed for cells exposed to more than 50 µg/mL G-OH over 72 h, suggesting G-OH caused cell apoptosis was slight. The G-OH induced DNA damage was also found to be mild since expression of p53 and ROS regeneration level was quite low even at high concentration of G-OH over a long time. Cell viability was found to be higher than 90% with 50 µg/mL G-OH and 80% with 100 µg/mL G-OH using flow cytometry. Comet results suggested that less than 5% tail could be found with 100 µg/mL G-OH. TEM results confirmed that G-OH could penetrate into and out of the cytoplasm by means of endocytosis and exocytosis without causing damage on cell membranes. In vivo biocompatibility of G-OH was studied by intravitreal injection of G-OH into rabbits. The ocular fundus photography results showed that G-OH could be diffused in the vitreous body gradually without any damage caused. Injection of G-OH had caused few damages on eyesight related functions such as intraocular pressure, electroretinogram and histological structures of the retina.

[Cleaning effect of ultrasonic activation as an adjunct to syringe irrigation of root canals: a systematic review].

OBJECTIVE: To investigate evidence supporting whether ultrasonic irrigation as a supplement is more effective than syringe irrigation in root canal cleaning. METHODS: An electronic search was conducted in PubMed, Embase, Web of Science, Cochrane Library, ProQuest Dissertation and Theses, Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, Wanfang Database, and Chinese Biomedical Literature Database. Studies were retrieved from January 1, 1985 to March 1, 2014. The Chinese journals on stomatology and the bibliography of all relevant articles were manually searched. Relevant clinical randomized controlled trial (RCT) and clinical controlled trial (CCT) were selected. Two investigators evaluated the risk of bias of the included trials in accordance with Cochrane risk of bias assessment tools and collected data of included studies. Meta-analysis was then performed in RevMan 5.2. RESULTS: Nine articles that satisfied the eligibility criteria were included in this Meta-analysis. Seven studies showed low bias risk, and the remaining studies exhibited moderate bias risk. Histological results showed that ultrasonic irrigation supplement could significantly improve canal and isthmus debridement at the apical area (P < 0.01). Antibacterial efficacy was evaluated by bacterial culture (P = 0.26) and polymerase chain reaction (P = 0.99) methods, no significant differences in antibacterial efficacy were observed. CONCLUSION: Ultrasonic irrigation supplement is more effective than syringe irrigation in root canal debridement at the apical area. However, antibacterial efficacy is not statistically significant.

[Application of role-play simulation in pre-clinical practice of the fourth grade students in department of endodontics].

PURPOSE: To apply role- play simulation in pre-clinical practice of the fourth grade students in department of endodontics. METHODS: Thirty-two students were randomly divided into 2 groups, there were 16 students in each group. Students in one group were taught with role-play simulation while the other group with lecture-based learning method. The teaching effect was measured with examination and questionnaire survey. The data was analyzed by using SPSS 17.0 software package. RESULTS: There were no significant differences in basic knowledge, case analysis and oral examination between 2 groups (P>0.05), but there was significant difference in history taking and medical records writing, practical examination and total scores between 2 groups (P<0.05). The role-play simulation was generally approved by both teachers and students in experimental group. CONCLUSIONS: The abilities of the fourth grade students can be developed by role-play simulation in different aspects. Role-play simulation can be applied in pre-clinical practice of the fourth grade students in department of endodontics.

Folate-modified poly(2-ethyl-2-oxazoline) as hydrophilic corona in polymeric micelles for enhanced intracellular doxorubicin delivery.

The transmembrane transport of drug loaded micelles to intracellular compartment is quite crucial for efficient drug delivery. In the current study, we investigated the cellular internalization and anticancer activity of doxorubicin loaded micelles with folate modified stealthy PEOz corona. Folate-decorated micelles incorporating doxorubicin were characterized for particle size, degree of folate decoration, drug loading content and encapsulation efficiency, morphology, and surface charge. The targeting capability and cell viability were assessed using HeLa, KB, A549 and MCF-7/ADR cell lines. In vitro study clearly illustrated the folate receptor (FR) mediated targeting of FA modified micelles to FR-positive human HeLa, KB and MCF-7/ADR cells, while specific delivery to FR-negative A549 cells was not apparently increased at the same experimental conditions. Cytotoxicity assay showed 60% and 58% decrease in IC50 values for HeLa and KB cells, while only a slight decrease for A549 cells, following treatment with folate modified formulations. The enhanced intracellular delivery of FA modified micelles in MCF-7/ADR cells was also observed. In vivo antitumor tests revealed DOX entrapped FA-PEOz-PCL micelles effectively inhibited the tumor growth and reduced the toxicity to mice compared with free DOX. The current study showed that the targeted nano-vector improved cytotoxicity of DOX and suggested that this novel PEOz endowed stealthy micelle system held great promise in tumor targeted therapy.

[The ultrastructure and activities of free radical scavenger in discolored gingiva adjacent to porcelain fused to metal crowns].

PURPOSE: This study was designed to study the discolored gingiva adjacent to porcelain fused to metal (PFM) crowns in terms of ultrastructure , SOD and GSH activities in 40 cases. METHODS: The discolored gingival ultrastructures were observed and metal X-ray energy level was analyzed;The activities of SOD and GSH were measured and compared with normal control by student's t test and one-way ANOVA with SPSS10.0 software package. RESULTS: The discolored gingival ultrastructure had changes compared with the normal gingiva. Nickel and chromium were not found in the particles through X-ray energy machine within the discolored gingiva adjacent to PFM crown. The activities of SOD and GSH in discolored gingiva were significantly different from control(P<0.05) and the values at 6 to 18 months were significantly different from those at other times. CONCLUSION: The ultrastructure underwent changes in discolored gingiva after PFM restoration; the activity of SOD and GSH in discolored gingiva changed to result in apoptosis, and discoloration.

[Research on the effect of root canal seal achieved by irradiation of Er, Cr:YSGG laser].

PURPOSE: To evaluate the effect of root canal seal achieved by routine root canal preparation and irradiation of Er, Cr:YSGG laser in root canal therapy. METHODS: One hundred and five freshly single-rooted extracted human teeth were selected for the study, which were randomly divided into seven groups of fifteen each. The anatomic crowns were removed at the cementoenamel junction and the remaining roots were prepared endodontically with conventional methods. Then they were treated with Er, Cr:YSGG laser in different parameters and patterns. The effect of root canal seal achieved by Er, Cr:YSGG laser was evaluated with microleakage measurements. Newman-Keuls test and one-way analysis of variance were used to determine the statistical differences between various groups. A value of P<0.05 was considered to be significant. RESULTS: The amount of dye penetration from an apical stop with irradiation of Er, Cr:YSGG laser was significantly lower (P<0.05) except 3W laser without water flow, and in 1W Er, Cr:YSGG laser without water flow, the amount of apical dye penetration was significantly decreased (P<0.01). CONCLUSIONS: The utilizing of Er, Cr:YSGG laser in small parameters prior to root canal filling could promote the effect of apical seal. Based on our results, it appeared that the seal effect of 1W Er, Cr:YSGG laser without water flow was superior to the effects of others.