[Effects of different exercise modes on neuromuscular junction and metabolism of skeletal muscle-related proteins in aging rats].

The present study aimed to explore the effects of different exercise modes on neuromuscular junction (NMJ) and metabolism of skeletal muscle-related proteins in aging rats. Ten from 38 male Sprague-Dawley (SD) rats (3-month-old) were randomly selected into young (Y) group, while the rest were raised to 21 months old and randomly divided into elderly control (O), endurance exercise (EN) and resistance exercise (R) groups. After 8 weeks of corresponding exercises training, the gastrocnemius muscles of rats were collected, and the expression of S100B in Schwann cells was detected by immunofluorescence staining. Western blot was used to detect the protein expression levels of agglutinate protein (Agrin), low-density lipoprotein receptor-related protein 4 (Lrp4), muscle- specific kinase protein (MuSK), downstream tyrosine kinase 7 (Dok7), phosphorylated protein kinase B (p-Akt), phosphorylated mammalian target rapamycin (p-mTOR), and phosphorylated forkhead box O1 (p-FoxO1) in rat gastrocnemius muscles. The results showed that, endurance and resistance exercises increased the wet weight ratio of gastrocnemius muscle in the aging rats. The protein expression of S100B in the R group was significantly higher than those in the O and EN groups. Proteins related to NMJ function, including Agrin, Lrp4, MuSK, and Dok7 were significantly decreased in the O group compared with those in the Y group. Resistance exercise up-regulated these four proteins in the aging rats, whereas endurance exercise could not reverse the protein expression levels of Lrp4, MuSK and Dok7. Regarding skeletal muscle-related proteins, the O group showed down-regulated p-Akt, and p-mTOR protein expression levels and up-regulated p-FoxO1 protein expression level, compared to the Y group. Resistance and endurance exercises reversed the changes in p-mTOR and p-FoxO1 protein expression in the aging rats. These findings demonstrate that both exercise modes can enhance NMJ function, increase protein synthesis and reduce the catabolism of skeletal muscle-related proteins in aging rats, with resistance exercise showing a more pronounced effect.

MicroRNA expression as a prognostic biomarker of tongue squamous cell carcinoma (TSCC): a systematic review and meta-analysis.

BACKGROUND: Recent studies have indicated that microRNA (miRNA) expression in tumour tissues has prognostic significance in Tongue squamous cell carcinoma (TSCC) patients. This study explored the possible prognostic value of miRNAs for TSCC based on published research. METHODS: A comprehensive literature search of multiple databases was conducted according to predefined eligibility criteria. Data were extracted from the included studies by two researchers, and HR results were determined based on Kaplan‒Meier curves according to the Tierney method. The Newcastle‒Ottawa Scale (NOS) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pro-GDT were applied to assess the quality of all studies. Publication bias was estimated by funnel plot, Egger's rank correlation test and sensitivity analysis. RESULTS: Eleven studies (891patients) were included, of which 6 reported up-regulated miRNAs and 7 mentioned down-regulated miRNAs. The pooled hazard ratio (HR) from the prognostic indicator overall survival (OS) was 1.34 (1.25-1.44), p < 0.00001, indicating a significant difference in miRNA expression between TSCC patients with better or worse prognosis. CONCLUSION: MiRNAs may have high prognostic value and could be used as prognostic biomarkers of TSCC.

[Comparison of the virtual surgical planning position of maxilla and condyle with the postoperative real position in patients with mandibular protrusion].

OBJECTIVE: To compare the difference between virtual surgical planning (VSP) position and postoperative real position of maxilla and condyle, and to explore the degree of intraoperative realization of VSP after orthognathic surgery. METHODS: In this study, 36 patients with mandibular protrusion deformity from January 2022 to December 2022 were included. All the patients had been done bilateral sagittal split ramus osteotomy (SSRO) combined with Le Fort Ⅰ osteotomy under guidance of VSP. The VSP data (T0) and 1-week postoperative CT (T1) were collected, the 3D model of postoperative CT was established and segmented into upper and lower jaws in CCMF Plan software. At the same time, accor-ding to the morphology of palatal folds, the virtual design was registered with the postoperative model, and the unclear maxillary dentition in the postoperative model was replaced. Then the postoperative model was matched with VSP model by registration of upper skull anatomy that was not affected by the operation. The three-dimensional reference plane and coordinate system were established. Selecting anatomical landmarks and their connections of condyle and maxilla for the measurement, we compared the coordinate changes of marker points in three directions, and the angle changes between the line connecting the marker points and the reference plane to analyze the positional deviation and the angle deviation of the postoperative condyle and maxilla compared to VSP. RESULTS: The postoperative real position of the maxilla deviates from the VSP by nearly 1 mm in the horizontal and vertical directions, and the anteroposterior deviation was about 1.5 mm. In addition, most patients had a certain degree of counterclockwise rotation of the maxilla after surgery. Most of the bilateral condyle moved forward, outward and downward (the average distance deviation was 0.15 mm, 1.54 mm, 2.19 mm, respectively), and rotated forward, outward and upward (the average degree deviation was 4.32°, 1.02°, 0.86°, respectively) compared with the VSP. CONCLUSION: VSP can be mostly achieved by assistance of 3D printed occlusal plates, but there are certain deviations in the postoperative real position of maxilla and condyle compared with VSP, which may be related to the rotation axis of the mandible in the VSP. It is necessary to use patient personalized condylar rotation axis for VSP, and apply condylar positioning device to further improve surgical accuracy.

Hesperetin promotes bladder cancer cells death via the PI3K/AKT pathway by network pharmacology and molecular docking.

Patients with bladder cancer (BLCA) still show high recurrence after surgery and chemotherapy. Hesperetin (HE), as a natural compound, has attracted researchers' attention due to its low toxicity and easy access. However, the inhibitory effect of HE on BLCA remains unknown. The hub genes and enrichment pathways regulated by HE in the treatment of BLCA were predicted by network pharmacology. The molecular docking of HE and hub proteins was visualized. Colony and CCK8 assays were used to test cell proliferation, and BLCA migration was confirmed by transwell and wound healing assays. In addition, the occurrence of apoptosis and ferroptosis was demonstrated by Hoechst staining, transmission electron microscopy (TEM) and ROS (reactive oxygen species) assay. Western Blotting was performed to validate the hub proteins, target functions and pathways. SRC, PIK3R1 and MAPK1 were identified as hub targets for HE in BLCA, involving the PI3k/AKT pathway. Furthermore, HE inhibited the proliferation and migration of BLCA cells. The MMP2/MMP9 proteins were significantly inhibited by HE. The increased expression of Bax and cleaved caspase-3 indicated that HE could promote BLCA cell apoptosis. In addition, Hoechst staining revealed concentrated and illuminated apoptotic nuclei. The activation of ROS and the decline of GPX4 expression suggested that HE might induce ferroptosis as an anti-BLCA process. Shrunk mitochondria and apoptotic bodies were observed in BLCA cells treated with HE, with reduced or absent mitochondrial cristae. We propose for the first time that HE could inhibit the proliferation and migration of BLCA cells and promote apoptosis and ferroptosis. HE may act by targeting proteins such as SRC, PIK3R1 and MAPK1 and the PI3K/AKT pathway.

Tumor keratin 15 expression links with less extent of invasion and better prognosis in papillary thyroid cancer patients receiving tumor resection.

OBJECTIVE: Keratin 15 (KRT15) is identified as a useful biomarker in several solid tumors, while its clinical role in papillary thyroid cancer (PTC) remains unknown. Herein, this study is intended to explore the correlation of tumor KRT15 with clinical features and survival in PTC patients who received tumor resection. METHODS: This study retrospectively screened 350 PTC patients who received tumor resection and 50 thyroid benign lesions (TBL) patients. KRT15 in formalin-fixed paraffin-embedded lesion specimens of all subjects was detected by immunohistochemistry (IHC). RESULTS: KRT15 was reduced in PTC patients compared to TBL patients (P < 0.001). Furthermore, KRT15 was negatively associated with tumor size (P = 0.017), extrathyroidal invasion (P = 0.007), pathological tumor (pT) stage (P < 0.001), and postoperative radioiodine application (P = 0.008) in PTC patients. Regarding prognostic value, high KRT15 (cut-off by an IHC value of 3) is linked with prolonged accumulating disease-free survival (DFS) (P = 0.008) and overall survival (OS) (P = 0.008) in PTC patients. Also, the multivariate Cox regression model showed that high KRT15 (vs. low) was an independent factor for longer DFS (hazard ratio = 0.433, P = 0.049), but not for OS (P > 0.050) in PTC patients. Subgroup analyses revealed that KRT15 possessed a better prognostic value in PTC patients with age ≥ 55 years, tumor size > 4 cm, pathological node stage 1, or pathological tumor-node-metastasis stage ≤ 2 (all P < 0.050). CONCLUSION: Increased tumor KRT15 associates with a lower invasive degree, prolonged DFS, and OS, revealing its prognostic utility in PTC patients undergoing tumor resection.

Daurisoline attenuates H2O2-induced chondrocyte autophagy by activating the PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage degeneration and intra-articular inflammation. Daurisoline (DAS) is an isoquinoline alkaloid isolated from Rhizoma Menispermi, whose antitumor and anti-inflammatory pharmacological effects have been demonstrated, but the effects of DAS on OA have rarely been researched. In this study, we aimed to explore the potential role of DAS in OA and its partial mechanism. MATERIALS AND METHODS: The cytotoxicity of H2O2 and DAS toward chondrocytes was detected by the Cell Counting Kit-8 assay. Safranin O staining was used to detect chondrocyte phenotype changes. Cell apoptosis was measured by both flow cytometry and quantitative analysis of the protein levels of the apoptosis-related factors Bax, Bcl-2 and cleaved caspase-3 by western blot. Western blotting and immunofluorescence were used to assess the expression of the autophagy-related proteins LC3, Beclin-1 and p62. In addition, key signal pathway targets and matrix-degrading indicators were measured by western blot. RESULTS: Our results indicated that H2O2 induced human chondrocyte apoptosis and activated autophagy in a dose-dependent manner. DAS treatment dose-dependently reversed the expression of apoptosis-related proteins (Bax, Bcl-2 and cleaved caspase3) and the apoptosis rate induced by H2O2. Western blot and immunofluorescence analyses showed that DAS decreased the H2O2-induced upregulation of the autophagy marker Beclin-1 and the LC3 II/LC3 I ratio and upregulated the p62 protein level. Mechanistically, DAS inhibited autophagy through the activation of the classical PI3K/AKT/mTOR signaling pathway and protected chondrocytes from apoptosis. In addition, DAS alleviated the H2O2-induced degradation of type II collagen and the high expression of matrix metalloproteinase 3 (MMP3) and MMP13. CONCLUSION: Our research demonstrated that DAS alleviated chondrocyte autophagy caused by H2O2 through activation of the PI3K/AKT/mTOR signaling pathway and protected chondrocytes from apoptosis and matrix degradation. In conclusion, these findings suggest that DAS may serve as a promising therapeutic strategy for OA.

Metformin enhances the osteogenic activity of rat bone marrow mesenchymal stem cells by inhibiting oxidative stress induced by diabetes mellitus: an in vitro and in vivo study.

PURPOSE: The purpose of this study was to determine whether metformin (MF) could alleviate the expresssion of reactive oxygen species (ROS) and improve the osteogenic ability of bone marrow mesenchymal stem cells derived from diabetic rats (drBMSCs) in vitro, and to evaluate the effect of MF on the ectopic osteogenesis of drBMSCs in a nude mouse model in vivo. METHODS: BMSCs were extracted from normal and diabetic rats. In vitro, a cell viability assay (Cell Counting Kit-8), tests of alkaline phosphatase (ALP) activity, and western blot analysis were first used to determine the cell proliferation and osteogenic differentiation of drBMSCs that were subjected to treatment with different concentrations of MF (0, 50, 100, 200, 500 µM). The cells were then divided into 5 groups: (1) normal rat BMSCs (the BMSCs derived from normal rats group), (2) the drBMSCs group, (3) the drBMSCs + Mito-TEMPO (10 µM, ROS scavenger) group, (4) the drBMSCs + MF (200 µM) group, and (5) the drBMSCs + MF (200 µM) + H2O2 (50 µM, ROS activator) group. Intracellular ROS detection, a senescence-associated ß-galactosidase assay, ALP staining, alizarin red staining, western blotting, and immunofluorescence assays were performed to determine the effects of MF on oxidative stress and osteogenic differentiation in drBMSCs. In vivo, the effect of MF on the ectopic osteogenesis of drBMSCs was evaluated in a nude mouse model. RESULTS: MF effectively reduced ROS levels in drBMSCs. The cell proliferation, ALP activity, mineral deposition, and osteogenic-related protein expression of drBMSCs were demonstrably higher in the MF-treated group than in the non-MF-treated group. H2O2 inhibited the effects of MF. In addition, ectopic osteogenesis was significantly increased in drBMSCs treated with MF. CONCLUSIONS: MF promoted the proliferation and osteogenic differentiation of drBMSCs by inhibiting the oxidative stress induced by diabetes and enhenced the ectopic bone formation of drBMSCs in nude mice.

Properties of flavonoids in the treatment of bladder cancer (Review).

Given its high recurrence and rapid progress, bladder cancer (BLCA) treatment has become a major problem for clinicians. BLCA is difficult to control even with surgical resection and extensive use of chemotherapeutic drugs. The non-toxicity and ease of accessibility of natural compounds have attracted much attention in recent years. Flavonoids serve an essential role given their antioxidant, antibacterial, anticancer and cardiovascular properties. They are mainly divided into several subclasses; flavones, flavanones, flavonols, flavanols, anthocyanins isoflavones and chalcones. Over the years, the role of flavonoids in BLCA has been extensively studied. The present review provided a comprehensive overview of the classification of flavonoids and substantiate the role of epithelial-mesenchymal transition, cancer stem cells, angiogenesis, epigenetic regulation and programmed cell death in BLCA. The present review emphasized that flavonoids for BLCA treatment are worthy of further study and anti-BLCA drugs have huge prospects for clinical use.

DeepSeqPanII: An Interpretable Recurrent Neural Network Model With Attention Mechanism for Peptide-HLA Class II Binding Prediction.

Human leukocyte antigen (HLA) complex molecules play an essential role in immune interactions by presenting peptides on the cell surface to T cells. With significant deep learning progress, a series of neural network-based models have been proposed and demonstrated with their excellent performances for peptide-HLA class I binding prediction. However, there is still a lack of effective binding prediction models for HLA class II protein binding with peptides due to its inherent challenges. We present a novel sequence-based pan-specific neural network structure, DeepSeaPanII, for peptide-HLA class II binding prediction in this work. Our model is an end-to-end neural network model without the need for pre-or post-processing on input samples compared with existing pan-specific models. Besides state-of-the-art performance in binding affinity prediction, DeepSeqPanII can also extract biological insight on the binding mechanism over the peptide by its attention mechanism-based binding core prediction capability. The leave-one-allele-out cross-validation and benchmark evaluation results show that our proposed network model achieved state-of-the-art performance in HLA-II peptide binding. The source code and trained models are freely available at https://github.com/pcpLiu/DeepSeqPanII.

The extract of concentrated growth factor enhances osteogenic activity of osteoblast through PI3K/AKT pathway and promotes bone regeneration in vivo.

BACKGROUND: Concentrated growth factor (CGF) is a third-generation platelet concentrate product; the major source of growth factors in CGF is its extract; however, there are few studies on the overall effects of the extract of CGF (CGF-e). The aim of this study was to investigate the effect and mechanism of CGF-e on MC3T3-E1 cells in vitro and to explore the effect of combination of CGF-e and bone collagen (Bio-Oss Collagen, Geistlich, Switzerland) for bone formation in cranial defect model of rats in vivo. METHODS: The cell proliferation, ALP activity, mineral deposition, osteogenic-related gene, and protein expression were evaluated in vitro; the newly formed bone was evaluated by histological and immunohistochemical analysis through critical-sized cranial defect rat model in vivo. RESULTS: The cell proliferation, ALP activity, mineral deposition, osteogenic-related gene, and protein expression of CGF-e group were significantly increased compared with the control group. In addition, there was significantly more newly formed bone in the CGF-e + bone collagen group, compared to the blank control group and bone collagen only group. CONCLUSIONS: CGF-e activated the PI3K/AKT signaling pathway to enhance osteogenic differentiation and mineralization of MC3T3-E1 cells and promoted the bone formation of rat cranial defect model.

Enhanced Magnetic Properties of FeSiAl Soft Magnetic Composites Prepared by Utilizing PSA as Resin Insulating Layer.

Thermosetting organic resins are widely applied as insulating coatings for soft magnetic powder cores (SMPCs) because of their high electrical resistivity. However, their poor thermal stability and thermal decomposition lead to a decrease in electrical resistivity, thus limiting the annealing temperature of SMPCs. The large amount of internal stress generated by soft magnetic composites during pressing must be mitigated at high temperatures; therefore, it is especially important to find organic resins with excellent thermal stabilities. In this study, we prepared SMPCs using poly-silicon-containing arylacetylene resin, an organic resin resistant to high temperatures, as an insulating layer. With 2 wt % PSA as an insulating layer and annealed at 700 °C for 1 h, the FeSiAl SMPCs achieved the best magnetic properties, including the lowest core loss of 184 mW/cm3 (measured at 0.1 T and 50 kHz) and highest permeability of 96.

Deep learning pan-specific model for interpretable MHC-I peptide binding prediction with improved attention mechanism.

Accurate prediction of peptide binding affinity to the major histocompatibility complex (MHC) proteins has the potential to design better therapeutic vaccines. Previous work has shown that pan-specific prediction algorithms can achieve better prediction performance than other approaches. However, most of the top algorithms are neural networks based black box models. Here, we propose DeepAttentionPan, an improved pan-specific model, based on convolutional neural networks and attention mechanisms for more flexible, stable and interpretable MHC-I binding prediction. With the attention mechanism, our ensemble model consisting of 20 trained networks achieves high and more stabilized prediction performance. Extensive tests on IEDB's weekly benchmark dataset show that our method achieves state-of-the-art prediction performance on 21 test allele datasets. Analysis of the peptide positional attention weights learned by our model demonstrates its capability to capture critical binding positions of the peptides, which leads to mechanistic understanding of MHC-peptide binding with high alignment with experimentally verified results. Furthermore, we show that with transfer learning, our pan model can be fine-tuned for alleles with few samples to achieve additional performance improvement. DeepAttentionPan is freely available as an open-source software at https://github.com/jjin49/DeepAttentionPan.

The effect of bone morphogenetic protein 2 composite materials combined with cannulated screws in treatment of acute displaced femoral neck fractures.

The risk of avascular necrosis (AVN) and nonunion after treatment of displaced femoral neck fractures is increased in patients aged <60 years. Therefore we established a new protocol for closed reduction and internal fixation (CRIF) using cannulated screws combined with bone morphogenetic protein 2 (BMP-2) composite materials to treat acute femoral neck fractures.This study enrolled 78 patients with acute femoral neck fractures between April 2014 and September 2016. We treated 46 patients with a mean age of 43.8 years in study group. These patients were treated by CRIF combined with BMP-2 composite materials. In control group, there were 32 patients with a mean age of 42.09 years. The patients were treated by CRIF without BMP-2. The duration between presentation and surgery, operative time, Harris score and complications were recorded.In study group, 43 patients were followed up with an average of 31.3 months. One patient suffered nonunion and three patients presented AVN. In control group, 28 patients were followed up with an average of 32.3 months, the rate of AVN and fracture nonunion were 25% (7/28) and 21.4% (6/28) respectively, significantly higher than those in study group (P < .05).Acute displaced femoral neck fractures can be treated with CRIF and BMP-2 composite materials in a minimally invasive manner. This technique was reproducible and had fewer complications.

A deep learning algorithm for one-step contour aware nuclei segmentation of histopathology images.

This paper addresses the task of nuclei segmentation in high-resolution histopathology images. We propose an automatic end-to-end deep neural network algorithm for segmentation of individual nuclei. A nucleus-boundary model is introduced to predict nuclei and their boundaries simultaneously using a fully convolutional neural network. Given a color-normalized image, the model directly outputs an estimated nuclei map and a boundary map. A simple, fast, and parameter-free post-processing procedure is performed on the estimated nuclei map to produce the final segmented nuclei. An overlapped patch extraction and assembling method is also designed for seamless prediction of nuclei in large whole-slide images. We also show the effectiveness of data augmentation methods for nuclei segmentation task. Our experiments showed our method outperforms prior state-of-the-art methods. Moreover, it is efficient that one 1000×1000 image can be segmented in less than 5 s. This makes it possible to precisely segment the whole-slide image in acceptable time. The source code is available at https://github.com/easycui/nuclei_segmentation . Graphical Abstract The neural network for nuclei segmentation.

Concentrate Growth Factors Regulate Osteogenic Dysfunction of MC3T3-E1 Cells Induced by High Glucose Through PI3K/Akt Signaling Pathway.

INTRODUCTION: The aim of this study is to investigate the effects of Concentrate Growth Factors Extract (CGF-e) on the proliferation and osteogenic differentiation of MC3T3-E1 cells under high glucose condition. MATERIALS AND METHODS: MC3T3-E1 cells were divided into 4 groups including normal glucose (5.5-mM) group (control), high glucose (25.5-mM) group, normal glucose + CGF-e group, and high glucose + CGF-e group. The proliferation, osteogenic differentiation and mineralization of osteoblasts were evaluated, respectively, by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cytoskeleton analysis, alkaline phosphatase activity assay, alizarin red staining, and real-time polymerase chain reaction. Western blots analysis was used to explore the role of PI3K/Akt pathway. RESULTS: The viability, osteogenic differentiation, and mineralization of MC3T3-E1 cells were significantly decreased by high glucose. All observed osteogenic dysfunction were inhibited by CGF-e. Moreover, the PI3K/Akt pathway was activated by CGF-e. CONCLUSIONS: It was concluded that the soluble factors released by CGF could significantly attenuate high glucose-mediated MC3T3-E1 cells osteogenic dysfunction through the PI3K/Akt pathway.

DeepSeqPan, a novel deep convolutional neural network model for pan-specific class I HLA-peptide binding affinity prediction.

Interactions between human leukocyte antigens (HLAs) and peptides play a critical role in the human immune system. Accurate computational prediction of HLA-binding peptides can be used for peptide drug discovery. Currently, the best prediction algorithms are neural network-based pan-specific models, which take advantage of the large amount of data across HLA alleles. However, current pan-specific models are all based on the pseudo sequence encoding for modeling the binding context, which is based on 34 positions identified from the HLA protein-peptide bound structures in early works. In this work, we proposed a novel deep convolutional neural network model (DCNN) for HLA-peptide binding prediction, in which the encoding of the HLA sequence and the binding context are both learned by the network itself without requiring the HLA-peptide bound structure information. Our DCNN model is also characterized by its binding context extraction layer and dual outputs with both binding affinity output and binding probability outputs. Evaluation on public benchmark datasets shows that our DeepSeqPan model without HLA structural information in training achieves state-of-the-art performance on a large number of HLA alleles with good generalization capability. Since our model only needs raw sequences from the HLA-peptide binding pairs, it can be applied to binding predictions of HLAs without structure information and can also be applied to other protein binding problems such as protein-DNA and protein-RNA bindings. The implementation code and trained models are freely available at https://github.com/pcpLiu/DeepSeqPan .

Forkhead box O3 promotes colon cancer proliferation and drug resistance by activating MDR1 expression.

BACKGROUND: Globally, colon cancer (CC) is the third reason of tumor-related deaths. Previous reports indicate that Forkhead box O3 (FOXO3) is involved in the development of various tumors and may have different effects depending upon the types of tumors. Hence, this study was to examine the effects of FOXO3 on CC cells and uncover the possible mechanisms. METHODS: MTT and cell count assay were applied to analyze the viability of transfected CC cells. rVista, dual luciferase reporter assay, and chromatin immunoprecipitation assay were used to identify the downstream target of FOXO3 in HCT116 cells. The mRNA and protein abundance of FOXO3 and MDR1 were determined by quantitative PCR and Western blot, respectively. RESULTS: Forkhead box O3 stimulated the proliferation of both HCT116 and DLD1 cells. Moreover, FOXO3 overexpression inhibited doxorubicin sensitivity of HCT116 cells, while the knockout of FOXO3 by FOXO3 shRNA restored the doxorubicin sensitivity in doxorubicin-resistant HCT116 DR cells. Next, we found that FOXO3 directly bound to the promoter of MDR1 and enhanced MDR1 expression in HCT116 cells. MDR1 overexpression enhanced the viability and doxorubicin resistance of CC cells. Besides, MDR1 overexpression plasmid significantly abrogated the decrease in cell proliferation and resistance of HCT116 cells to doxorubicin caused by FOXO3 knockout. CONCLUSION: Forkhead box O3 exhibited promotive effects on the proliferation and doxorubicin resistance in CC cells via targeting MDR1.

Group 5 ITI Consensus Report: Digital technologies.

OBJECTIVES: Working Group 5 was assigned the task to review the current knowledge in the area of digital technologies. Focused questions on accuracy of linear measurements when using CBCT, digital vs. conventional implant planning, using digital vs. conventional impressions and assessing the accuracy of static computer-aided implant surgery (s-CAIS) and patient-related outcome measurements when using s-CAIS were addressed. MATERIALS AND METHODS: The literature was systematically searched, and in total, 232 articles were selected and critically reviewed following PRISMA guidelines. Four systematic reviews were produced in the four subject areas and amply discussed in the group. After emendation, they were presented to the plenary where after further modification, they were accepted. RESULTS: Static computer-aided surgery (s-CAIS), in terms of pain & discomfort, economics and intraoperative complications, is beneficial compared with conventional implant surgery. When using s-CAIS in partially edentulous cases, a higher level of accuracy can be achieved when compared to fully edentulous cases. When using an intraoral scanner in edentulous cases, the results are dependent on the protocol that has been followed. The accuracy of measurements on CBCT scans is software dependent. CONCLUSIONS: Because the precision intraoral scans and of measurements on CBCT scans and is not high enough to allow for the required accuracy, s-CAIS should be considered as an additional tool for comprehensive diagnosis, treatment planning, and surgical procedures. Flapless s-CAIS can lead to implant placement outside of the zone of keratinized mucosa and thus must be executed with utmost care.

Strontium ion attenuates lipopolysaccharide-stimulated proinflammatory cytokine expression and lipopolysaccharide-inhibited early osteogenic differentiation of human periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Periodontitis is a chronic inflammatory disease characterized by the destruction of the periodontium. The strontium ion (Sr2+ ) can prevent the bone loss associated with periodontitis and promote the regeneration of the bone. The mechanisms by which the Sr2+ works remain poorly understood. We aim to investigate the effects of the Sr2+ ion on cell proliferation, inflammatory regulation and osteogenic differentiation of human periodontal ligament cells (hPDLCs) in pathological conditions. MATERIAL AND METHODS: hPDLCs were obtained from premolars that came from the orthodontic extraction. The hPDLCs were treated with Sr2+ and/or lipopolysaccharide (LPS), which was applied as the pathological condition of periodontitis. The effect of the dose of Sr2+ on cell proliferation was analyzed using a Cell Counting Kit-8 assay. The gene and protein expression of proinflammatory cytokines were detected by the real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The osteogenic differentiation and mineralization were assessed by the real-time polymerase chain reaction, alkaline phosphatase activity assay and alizarin red staining. RESULTS: Results demonstrated that Sr2+ in a range of concentrations from 0.02 to 2.5 mmol/L significantly improved the proliferation of hPDLCs. Sr2+ reversed LPS-stimulated proinflammatory cytokine expressions such as tumor necrosis factor alpha, interleukin (IL)-1ß, IL-6 and IL-8. Moreover, Sr2+ rescued the LPS-inhibited gene expression of osteogenic differentiation. Although it appeared to suppress the late mineralization, Sr2+ can reverse the LPS-inhibited early osteogenic differentiation of hPDLCs. CONCLUSION: These results indicated that Sr2+ could attenuate the LPS-stimulated proinflammatory molecule expression and inhibit early osteogenic differentiation of hPDLCs.

Clinical Factors Affecting the Accuracy of Guided Implant Surgery-A Systematic Review and Meta-analysis.

OBJECTIVES: To systematically review the current dental literature regarding clinical accuracy of guided implant surgery and to analyze the involved clinical factors. MATERIAL AND METHODS: PubMed and Cochrane Central Register of Controlled Trials were searched. Meta-analysis and meta-regression analysis were performed. Clinical studies with the following outcome measurements were included: (1) angle deviation, (2) deviation at the entry point, and (3) deviation at the apex. The involved clinical factors were further evaluated. RESULTS: Fourteen clinical studies from 1951 articles initially identified met the inclusion criteria. Meta-regression analysis revealed a mean deviation at the entry point of 1.25 mm (95% confidence interval [CI]: 1.22-1.29), 1.57 mm (95% CI: 1.53-1.62) at the apex, and 4.1° in angle (95% CI: 3.97-4.23). A statistically significant difference (P < .001) was observed in angular deviations between the maxilla and mandible. Partially guided surgery showed a statistically significant greater deviation in angle (P < .001), at the entry point (P < .001), and at the apex (P < .001) compared with totally guided surgery. The outcome of guided surgery with flapless approach indicated significantly more accuracy in angle (P < .001), at the entry point (P < .001), and at apex (P < .001). Significant differences were observed in angular deviation based on the use of fixation screw (P < .001). CONCLUSIONS: The position of guide, guide fixation, type of guide, and flap approach could influence the accuracy of computer-aided implant surgery. A totally guided system using fixation screws with a flapless protocol demonstrated the greatest accuracy. Future clinical research should use a standardized measurement technique for improved accuracy.