Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/ß-catenin signaling pathways.

BACKGROUND: Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength. However, current anti-resorptive drugs carry a risk of various complications. The deep learning-based efficacy prediction system (DLEPS) is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes. This study aimed to explore the protective effect and potential mechanisms of cinobufotalin (CB), a traditional Chinese medicine (TCM), on bone loss. METHODS: DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis. Micro-CT, histological and morphological analysis were applied for the bone protective detection of CB, and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells (hBMMSCs) were also investigated. The underlying mechanism was verified using qRT-PCR, Western blot (WB), immunofluorescence (IF), etc. RESULTS: A safe concentration (0.25 mg/kg in vivo, 0.05 µM in vitro) of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs. Both BMPs/SMAD and Wnt/ß-catenin signaling pathways participated in CB-induced osteogenic differentiation, further regulating the expression of osteogenesis-associated factors, and ultimately promoting osteogenesis. CONCLUSION: Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss, further promoting osteogenic differentiation/function of hBMMSCs, with BMPs/SMAD and Wnt/ß-catenin signaling pathways involved.

Network meta-analysis of the treatment efficacy of different lasers for peri-implantitis.

The aim of this study was comparing different lasers with conventional non-surgical treatment (CNT) for the management of peri-implantitis, regarding probing depth (PD), plaque index (PLI), clinical attachment level (CAL), and sulcus bleeding index (SBI). Randomized controlled trials (RCTs) on different lasers and CNT for peri-implantitis were searched. Pairwise and network meta-analyses were performed to analyze the PD, PLI, CAL, and SBI outcomes. The risk of bias, evidence quality, statistical heterogeneity, and ranking probability were also evaluated. Eleven studies were included in this study, involving three types of lasers. Diode + CNT had significantly superior efficacy to CNT alone, regarding PD reduction, while Er:YAG + CNT had significantly superior efficacy than CNT in terms of the PLI, CAL, and SBI. The highest probability of being most effective for PD was diode + CNT (49%), while Er:YAG + CNT had the highest probability of improving the PLI, CAL, and SBI (66%, 53%, and 79%, respectively). Diode + CNT was significantly superior for PD management in peri-implantitis compared with CNT alone, while Er:YAG + CNT significantly improved the PLI, CAL, and SBI. Therefore, Er:YAG + CNT might be recommended methods considered for management of peri-implantitis.

The evaluation of the desensitization effect of a desensitizing agent and desensitizing toothpastes in vitro.

This study was evaluating how three desensitizing toothpastes used at home influence the effect associated with desensitizing agents after application in the clinic. Fifty dentine disks measure it permeability and 32 dentine disks with similar permeability levels were selected. Following Dental desensitizer treatment, dentine disks were randomly divided into three subgroups (n=10) that received applications of three toothpastes, respectively. The permeability (Lp) of each specimen was measured after each treatment. One specimen was selected from each group for scanning electron microscopy (SEM) observation. After each treatment, the Lp values decreased significantly for each group (p<0.05) and either completely or partially blocked the dentine tubules upon SEM observation. However, no significant differences in Lp values were observed amongst subgroups (p>0.05). After using the Dental desensitizer, Sensodyne, Crest and Colgate desensitizing toothpastes both can continued to reduce the permeability of the dentine disk, and no significant differences were found amongst them.

Comparison of technical, biological, and esthetic parameters of ceramic and metal-ceramic implant-supported fixed dental prostheses: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Differences between ceramic and metal-ceramic implant-supported fixed dental prostheses are unclear. PURPOSE: The purpose of this systematic review and meta-analysis was to compare the technical, biological, and esthetic complication rates of implant-supported ceramic and metal-ceramic restorations. MATERIAL AND METHODS: Six databases were searched to identify randomized controlled clinical trials (RCTs) and prospective and retrospective cohort studies of implant-supported fixed dental prostheses. The survival rate, marginal adaptation, marginal bone loss, pocket probing depth, crown color match, and mucosal discoloration of ceramic and metal-ceramic single crowns were assessed. For implant-supported fixed partial dental prostheses (FPDPs), only the survival rate was assessed. The risk of bias was assessed for individual studies and across studies by using the Cochrane guidelines, Newcastle-Ottawa scale, and funnel plots. RESULTS: Twenty studies were included in this meta-analysis. Ceramic and metal-ceramic implant-supported single crowns were compared in terms of the survival rate (OR=0.84 [0.32, 2.23], P=.730), marginal adaptation (mean difference [MD]=0.33 [0.19, 0.47], P<.001), marginal bone loss (MD=-0.03 [-0.07, 0.02], P=.260), pocket probing depth (MD=-0.07 [-0.14, 0.00], P=.060), crown color match (MD=-0.15 [-0.29, 0.00], P=.040), and mucosal discoloration (standardized mean difference [SMD]=-0.14 [-0.86, 0.58], P=.710). The survival rate of ceramic and metal-ceramic implant-supported FPDPs was also compared (odds ratio [OR]=1.92 [1.26, 2.94], P=.003). CONCLUSIONS: No significant difference was observed between ceramic and metal-ceramic implant-supported single crowns in terms of the survival rate, marginal bone loss, pocket probing depth, or mucosal discoloration. However, metal-ceramic single crowns had better marginal adaptation and poorer crown color match than did ceramic single crowns. In addition, current evidence indicates that metal-ceramic implant-supported FPDPs might have a higher survival rate than ceramic FPDPs.

Effect of Lasers on Dentine Hypersensitivity: Evidence From a Meta-analysis.

OBJECTIVES: The aim of the study was to evaluate the immediate and long-term desensitizing effect of lasers in reducing dentine hypersensitivity (DH) compared with negative controls. MATERIAL AND METHODS: Six databases were searched to identify relevant articles published up to June 8, 2018. Randomized controlled trials comparing lasers with placebo or no treatment control in adult patients who suffer from DH were included. The risk of bias was assessed according to the Cochrane guidelines, and the quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation tool. Inverse-variance random effects meta-analyses of standardized mean differences and 95% confidence intervals were performed using the RevMan 5.3 software. RESULTS: Twenty-two randomized controlled trials were finally included in the meta-analysis, and 21 studies of these were conducted to analyze the immediate and long-term effects. All types of lasers had better immediate and long-term desensitizing effects on DH than negative controls. The quality of evidence of the included studies showed that lasers compared with negative controls had moderate-quality immediate and long-term effects on DH. The statistical heterogeneity of these comparisons was high, for which the result of I2 ranged from 90% to 98%. CONCLUSIONS: Our results indicate that all types of lasers had a better desensitizing effect on DH than negative controls, both in immediate and long term. Furthermore, more high-quality studies with a large sample size are needed to confirm our results (PROSPERO CRD42018102260).

Network meta-analysis on the effect of desensitizing toothpastes on dentine hypersensitivity.

OBJECTIVES: This network meta-analysis compares different desensitizing toothpastes and placebo in terms of their effects on dentine hypersensitivity (DH) at 2, 4, and 8 weeks. MATERIALS AND METHODS: A systematic electronic literature search of four databases, and a manual search, were performed to identify randomized controlled trials (RCTs) on different desensitizing toothpastes for the treatment of DH. Pair-wise and network meta-analyses were performed to analyze the desensitization effect at 2, 4, and 8 weeks. The risk of bias was assessed based on the Cochrane guidelines and funnel plots. Statistical heterogeneity, inconsistencies, and ranking probability were also evaluated. RESULTS: A total of 30 RCTs were included in the network meta-analysis, which included eight desensitizing toothpastes. There was no significant difference in the effect among calcium sodium phosphosilicate-containing (CSPS), potassium-containing (K) and strontium-containing (Sr) toothpastes. In addition, there was no significant difference between fluoride (F) and placebo. The desensitizing toothpaste with the highest probability of being the most effective treatment for DH was nano-hydroxyapatite (n-HA) at 2 and 4 weeks (60% and 67%, respectively), and Ar at 8 weeks (54%). CONCLUSIONS: No significant difference was detected in desensitizing effects among CSPS, K and Sr toothpastes. In addition, there was no significant difference between F and placebo, K and placebo. Furthermore, a significant placebo effect on DH was found in this study. Moreover, n-HA toothpastes may be the best desensitizing toothpastes for treatment of DH, followed by Ar toothpaste. CLINICAL SIGNIFICANCE: Based on the results of present network meta-analysis, n-HA containing toothpastes might be a recommended desensitizing toothpastes considering the treatment of DH. PROSPERO registration number: CRD42019117710.

Effect of desensitizing toothpastes on dentine hypersensitivity: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the desensitizing effect of toothpastes that contain ingredients that act against dentine hypersensitivity (DH) and to compare this effect with negative controls. SOURCES: Five databases were searched to identify relevant articles published up to November 27, 2017. STUDY SELECTION: Randomized controlled trials (RCTs) comparing desensitizing toothpastes with a toothpastes without desensitizing component in adult patients that suffer from DH were included. The risk of bias was assessed according to the Cochrane guidelines, and the quality of the evidence was evaluated using the GRADE tool. Inverse variance random-effects meta-analyses of standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated using RevMan 5.3 software. DATA: 53 RCTs with 4796 patients were finally included in the meta-analysis. The toothpastes that contain active desensitization ingredients showed a better desensitizing effect on DH than the negative control, except the strontium- and amorphous calcium phosphate-containing toothpastes. The amorphous calcium phosphate-containing toothpaste had very low-quality evidence, the strontium, potassium and strontium, and potassium and stannous fluoride-containing toothpastes had low-quality evidence, and the other five toothpastes had moderate quality evidence. CONCLUSIONS: Our result support the premise that toothpastes containing potassium, stannous fluoride, potassium and strontium, potassium and stannous fluoride, calcium sodium phosphosilicate, arginine, and nano-hydroxyapatite relieve the symptoms of DH, but does not advise the use of toothpastes that contain strontium and amorphous calcium phosphate. Furthermore, high-quality studies are needed to confirm our results. (PROSPERO CRD42018085639).

Porous zirconia ceramic as an alternative to dentin for in vitro dentin barriers cytotoxicity test.

OBJECTIVES: This study assessed the potential of porous zirconia ceramic as an alternative to dentin via an in vitro dentin barrier cytotoxicity test. METHODS: The permeability of dentin and porous zirconia ceramic was measured using a hydraulic-conductance system, and their permeability was divided into two groups: high and low. Using an in vitro dentin barrier test, the cytotoxicity of dental materials by dentin and porous zirconia ceramic was compared within the same permeability group. The L-929 cell viability was assessed by MTT assay. RESULTS: The mean (SD) permeability of the high and low group for dentin was 0.334 (0.0873) and 0.147 (0.0377) µl min-1 cm-2 cm H2O-1 and for zirconia porous ceramic was 0.336 (0.0609) and 0.146 (0.0340) µl min-1 cm-2 cm H2O-1. The cell viability of experimental groups which are the low permeability group was higher than that of the high permeability group for both dentin and porous zirconia ceramic as a barrier except for Maxcem Elite™ by porous zirconia ceramic. There was no significant difference between dentin and porous zirconia ceramic in cell viability, within either the high or low permeability group for all materials. The SD for cell viability of the porous zirconia ceramic was less than that of the dentin, across all materials within each permeability group, except for Maxcem Elite™ in the high permeability group. CONCLUSIONS: Porous zirconia ceramic, having similar permeability to dentin at the same thickness, can be used as an alternative to dentin for in vitro dentin barrier cytotoxicity tests. CLINICAL RELEVANCE: In vitro dentin barrier cytotoxicity tests when a standardized porous zirconia ceramic was used as a barrier could be useful for assessing the potential toxicity of new dental materials applied to dentin before applying in clinical and may resolve the issue of procuring human teeth when testing proceeds.

"Perfect" designer chromosome V and behavior of a ring derivative.

Perfect matching of an assembled physical sequence to a specified designed sequence is crucial to verify design principles in genome synthesis. We designed and de novo synthesized 536,024-base pair chromosome synV in the "Build-A-Genome China" course. We corrected an initial isolate of synV to perfectly match the designed sequence using integrative cotransformation and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated editing in 22 steps; synV strains exhibit high fitness under a variety of culture conditions, compared with that of wild-type V strains. A ring synV derivative was constructed, which is fully functional in Saccharomyces cerevisiae under all conditions tested and exhibits lower spore viability during meiosis. Ring synV chromosome can extends Sc2.0 design principles and provides a model with which to study genomic rearrangement, ring chromosome evolution, and human ring chromosome disorders.

Enhanced Bioconversion of Cellobiose by Industrial Saccharomyces cerevisiae Used for Cellulose Utilization.

Cellobiose accumulation and the compromised temperature for yeast fermentation are the main limiting factors of enzymatic hydrolysis process during simultaneous saccharification and fermentation (SSF). In this study, genes encoding cellobiose transporter and ß-glucosidase were introduced into an industrial Saccharomyces cerevisiae strain, and evolution engineering was carried out to improve the cellobiose utilization of the engineered yeast strain. The evolved strain exhibited significantly higher cellobiose consumption rate (2.8-fold) and ethanol productivity (4.9-fold) compared with its parent strain. Besides, the evolved strain showed a high cellobiose consumption rate of 3.67 g/L/h at 34°C and 3.04 g/L/h at 38°C. Moreover, little cellobiose was accumulated during SSF of Avicel using the evolved strain at 38°C, and the ethanol yield from Avicel increased by 23% from 0.34 to 0.42 g ethanol/g cellulose. Overexpression of the genes encoding cellobiose transporter and ß-glucosidase accelerated cellobiose utilization, and the improvement depended on the strain background. The results proved that fast cellobiose utilization enhanced ethanol production by reducing cellobiose accumulation during SSF at high temperature.

Optimization of CDT-1 and XYL1 expression for balanced co-production of ethanol and xylitol from cellobiose and xylose by engineered Saccharomyces cerevisiae.

Production of ethanol and xylitol from lignocellulosic hydrolysates is an alternative to the traditional production of ethanol in utilizing biomass. However, the conversion efficiency of xylose to xylitol is restricted by glucose repression, causing a low xylitol titer. To this end, we cloned genes CDT-1 (encoding a cellodextrin transporter) and gh1-1 (encoding an intracellular ß-glucosidase) from Neurospora crassa and XYL1 (encoding a xylose reductase that converts xylose into xylitol) from Scheffersomyces stipitis into Saccharomyces cerevisiae, enabling simultaneous production of ethanol and xylitol from a mixture of cellobiose and xylose (main components of lignocellulosic hydrolysates). We further optimized the expression levels of CDT-1 and XYL1 by manipulating their promoters and copy-numbers, and constructed an engineered S. cerevisiae strain (carrying one copy of PGK1p-CDT1 and two copies of TDH3p-XYL1), which showed an 85.7% increase in xylitol production from the mixture of cellobiose and xylose than that from the mixture of glucose and xylose. Thus, we achieved a balanced co-fermentation of cellobiose (0.165 g/L/h) and xylose (0.162 g/L/h) at similar rates to co-produce ethanol (0.36 g/g) and xylitol (1.00 g/g).

Balance of XYL1 and XYL2 expression in different yeast chassis for improved xylose fermentation.

Reducing xylitol formation is necessary in engineering xylose utilization in recombinant Saccharomyces cerevisiae for ethanol production through xylose reductase/xylitol dehydrogenase pathway. To balance the expression of XYL1 and mutant XYL2 encoding xylose reductase (XR) and NADP(+)-dependent xylitol dehydrogenase (XDH), respectively, we utilized a strategy combining chassis selection and direct fine-tuning of XYL1 and XYL2 expression in this study. A XYL1 gene under the control of various promoters of ADH1, truncated ADH1 and PGK1, and a mutated XYL2 with different copy numbers were constructed into different xylose-utilizing modules, which were then expressed in two yeast chassises W303a and L2612. The strategy enabled an improved L2612-derived recombinant strain with XYL1 controlled by promoter PGK1 and with two copies of XYL2. The strain exhibited a 21.3% lower xylitol yield and a 40.0% higher ethanol yield. The results demonstrate the feasibility of the combinatorial strategy for construction of an efficient xylose-fermenting S. cerevisiae.