Glioma-derived exosome Lncrna Agap2-As1 promotes glioma proliferation and metastasis by mediating Tgf-ß1 secretion of myeloid-derived suppressor cells.

Background: Glioma (GBM) is the most prevalent malignancy worldwide with high morbidity and mortality. Exosome-mediated transfer of long noncoding RNA (lncRNA) has been reported to be associated with human cancers, containing GBM. Meanwhile, myeloid-derived suppressor cells (MDSCs) play a vital role in mediating the immunosuppressive environments in GBM. Objectives: This study is designed to explore the role and mechanism of exosomal (Exo) lncRNA AGAP2-AS1 on the MDSC pathway in GBM. Methods: AGAP2-AS1, microRNA-486-3p (miR-486-3p), and Transforming growth factor beta-1 (TGF-ß1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, migration, and invasion were detected by 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and Transwell assays. E-cadherin, Vimentin, CD9, CD81, and TGF-ß1 protein levels were examined using Western blot. Exosomes were detected by a transmission electron microscope (TEM). Binding between miR-486-3p and AGAP2-AS1 or TGF-ß1 was predicted by LncBase or TargetScan and then verified using a dual-luciferase reporter assay. Results: AGAP2-AS1 was highly expressed in GBM tissues and cells. Functionally, AGAP2-AS1 absence or TGF-ß1 knockdown repressed tumor cell growth and metastasis. Furthermore, Exo-AGAP2-AS1 from GBM cells regulated TGF-ß1 expression via sponging miR-486-3p in MDSCs. Exo-AGAP2-AS1 upregulation facilitated GBM cell growth and metastasis via the MDSC pathway. Conclusion: Exo-AGAP2-AS1 boosted GBM cell development partly by regulating the MDSC pathway, hinting at a promising therapeutic target for GBM treatment.

The applications of the plasma matrix in the treatments of dental pulp and periapical diseases / 口腔疾病防治

@#The plasma matrix is a kind of autologous blood conduct. It has been widely used in maxillofacial tissue regeneration, skin cosmetology and some other fields. Recently, to preserve the dental pulp as well as the teeth, pulp regeneration therapy and apical surgery have become increasingly important as well as the applications of bioactive materials. As a kind of autologous bioactive material, the plasma matrix has some natural advantages as it is easy to obtain and malleable. The plasma matrix can be used in the following cases: ①pulp revascularization of young permanent teeth with open apical foramina that cannot stimulate apical bleeding; ② apical barrier surgery with bone defects and large area perforation repair with bone defects or root sidewall repair surgery; ③ apical surgeries of teeth with large area of apical lesions, with or without periodontal diseases. The plasma matrix is a product derived from our blood, and there are no obvious contraindications for its use. Several systematic reviews have shown that the plasma matrix can effectively promote the regenerative repair of dental pulp in patients with periapical diseases. However, the applications of plasma matrix are different because its characteristics are affected by different preparation methods. In addition, there is still a lack of long-term clinical researches on the plasma matrix, and the histological evidences are difficult to obtain, so a large number of in vitro and in vivo experimental studies are still needed. This article will describe the applications of different kinds of plasma matrix for dental pulp regeneration and bone tissue regeneration in apical surgeries to provide references for clinicians in indication selection and prognosis evaluation.

3D Bioprinting of a Bioactive Composite Scaffold for Cell Delivery in Periodontal Tissue Regeneration.

Hydrogels have been widely applied to the fabrication of tissue engineering scaffolds via three-dimensional (3D) bioprinting because of their extracellular matrix-like properties, capacity for living cell encapsulation, and shapeable customization depending on the defect shape. However, the current hydrogel scaffolds show limited regeneration activity, especially in the application of periodontal tissue regeneration. In this study, we attempted to develop a novel multi-component hydrogel that possesses good biological activity, can wrap living cells for 3D bioprinting and can regenerate periodontal soft and hard tissue. The multi-component hydrogel consisted of gelatin methacryloyl (GelMA), sodium alginate (SA) and bioactive glass microsphere (BGM), which was first processed into hydrogel scaffolds by cell-free 3D printing to evaluate its printability and in vitro biological performances. The cell-free 3D-printed scaffolds showed uniform porous structures and good swelling capability. The BGM-loaded scaffold exhibited good biocompatibility, enhanced osteogenic differentiation, apatite formation abilities and desired mechanical strength. The composite hydrogel was further applied as a bio-ink to load with mouse bone marrow mesenchymal stem cells (mBMSCs) and growth factors (BMP2 and PDGF) for the fabrication of a scaffold for periodontal tissue regeneration. The cell wrapped in the hydrogel still maintained good cellular vitality after 3D bioprinting and showed enhanced osteogenic differentiation and soft tissue repair capabilities in BMP2- and PDGF-loaded scaffolds. It was noted that after transplantation of the cell- and growth factor-laden scaffolds in Beagle dog periodontal defects, significant regeneration of gingival tissue, periodontal ligament, and alveolar bone was detected. Importantly, a reconstructed periodontal structure was established in the treatment group eight weeks post-transplantation of the scaffolds containing the cell and growth factors. In conclusion, we developed a bioactive composite bio-ink for the fabrication of scaffolds applicable for the reconstruction and regeneration of periodontal tissue defects.

Overexpression of MicroRNA-155 aggravates pulpitis by targeting kinesin superfamily Proteins-5C based on illumina high-throughput sequencing.

AIM: To investigate the regulatory role of miR-155 and Kinesin Superfamily Proteins-5C (KIF-5C) in the progression of pulpitis based on bioinformatic analysis. METHODOLOGY: Normal pulp tissues and pulpitis pulp tissues were collected and subjected to high-throughput sequencing and the differentially expressed miRNAs were determined. An in vitro and in vivo pulpitis model was established. HE, IHC staining and histological evaluation were used to verify the inflammatory state of human and mouse pulp tissues. The mRNA expression of IL-1ß and TGF-ß1 were determined by RT-qPCR and protein expression of IL-1α, IL-4, IL-8, IL-13, IFN-γ, IL-6, IL-10 and MCP-1 were determined by protein chip. The target genes of miR-155 were predicted by miRanda database and verified by Dual-luciferase reporter assay, RT-qPCR and western blotting. MiR-155 lentivirus were used to upregulate or downregulate miR-155 and the siRNA of KIF-5C was used to downregulate KIF-5C. The expression of miR-155 or KIF-5C was determined by RT-qPCR. All statistics were analysed using GraphPad prism 8.2. RESULTS: The high-throughput sequencing results showed that 6 miRNAs (miR-155, miR-21, miR-142, miR-223, miR-486, miR-675) were significantly upregulated in diseased human pulp tissues, and miR-155 was significantly elevated among the six miRNAs. RT-qPCR results demonstrated that miR-155 expression was upregulated in human pulpitic tissue, mice pulpitic tissue and LPS-HDPCs. IL-1ß was increased while TGF-ß1 was decreased in lenti-miR-155 transfected LPS-HDPCs. Analysis of protein chip results indicated that lenti-miR-155 transfected LPS-HDPCs produced higher levels of IL-8, IL-6, MCP-1. The opposite results were obtained when miR-155 was inhibited. Through miRanda database screen and Dual-luciferase reporter assay, the target gene (KIF-5C) of miR-155 was identified. In lenti-miR-155 transfected LPS-HDPCs, the expression of KIF-5C was downregulated. However, when shRNA-miR-155 was transfected to LPS-HDPCs, the opposite result was obtained. Silent RNA was used to knock down KIF-5C, the results showed that when both KIF-5C and miR-155 were knocked down simultaneously, the downregulated expression of inflammatory factors observed in LPS-HDPCs following miR-155 knockdown was rescued. CONCLUSION: MiR-155 plays an important role in promoting pulpitis through targeting KIF-5C and may serve as a potential therapeutic target.

Cx43 overexpression reduce the incidence of obstructive sleep apnea associated atrial fibrillation via the CaMK⠡γ/HIF-1 axis.

BACKGROUND: Previous studies by our group have demonstrated chronic intermittent hypoxia (CIH) can decrease connexin 43 (Cx43) protein expression and thus increase atrial fibrillation (AF) inducibility. Cardiac sympathetic denervation (CSD) can reduce AF and increase Cx43 expression, however, the underlying molecular mechanisms and signaling pathways are still unclear. METHODS AND RESULTS: An obstructive sleep apnea (OSA) rat model in vivo experiments and CIH H9c2 cells model in vitro experiments were used to figure out the roles and underlying mechanisms of Cx43 on OSA-associated AF. In this study, we examined the expression of Cx43, CaMKⅡγ, Bax, Caspase 3, HIF-1 Bcl-2, Tunel, and CPB/p300, to discover the association between proteins and the mechanism of regulatory changes. The downstream proteins of Cx43 were calculated by gene sequencing and data analysis. We found Cx43 expression was significantly downregulated after CIH exposure in rat and H9c2 cells. Active caspase-3 and Bax at CIH+8 h group are high, but decreased at OE+8 h group. The Bcl-2 expression was higher in the N and OE+8 h group than CIH+8 h group. TUNEL-positive cells from the CIH+8 h group was markedly higher. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated Cx43 overexpression inhibited the CaMKIIγ expression, and CaMKIIγ was involved in the HIF-1 signaling pathway. In addition, we also found Cx43 overexpression remarkably decreased the HIF-1 protein and p300 mRNA expression, which inhibits the CaMKIIγ/HIF-1 signaling pathway. CONCLUSIONS: Taken together, these results suggested Cx43 overexpression inhibits the expression of calcium/calmodulin dependent protein CaMKⅡγ via the Cx43/CaMKIIγ/HIF-1 axis, which finally reduces the myocardial apoptosis and incidence of AF.

Platelet-Membrane-Encapsulated Carvedilol with Improved Targeting Ability for Relieving Myocardial Ischemia-Reperfusion Injury.

In recent years, cell membrane drug delivery systems have received increasing attention. However, drug-loaded membrane delivery systems targeting therapy in myocardial ischemia-reperfusion injury (MIRI) have been relatively rarely studied. The purpose of this study was to explore the protective effect of platelet-membrane-encapsulated Carvedilol on MIRI. We extracted platelets from the blood of adult SD rats and prepared platelet membrane vesicles (PMVs). Carvedilol, a nonselective ß-blocker, was encapsulated into the PMVs. In order to determine the best encapsulation rate and drug-loading rate, three different concentrations of Carvedilol in low, medium, and high amounts were fused to the PMVs in different volume ratios (drugs/PMVs at 2:1, 1:1, 1:2, and 4:1) for determining the optimum concentration and volume ratio. By comparing other delivery methods, including abdominal injection and intravenous administration, the efficacy of PMVs-encapsulated drug-targeted delivery treatment was observed. The PMVs have the ability to target ischemic-damaged myocardial tissue, and the concentration and volume ratio at the optimum encapsulation rate and the drug-loading rate are 0.5 mg and 1:1. We verified that PMVs@Carvedilol had better therapeutic effects compared to other treatment groups, and immunofluorescence observation showed a significant improvement in the apoptosis indicators and infarction area of myocardial cells. Targeted administration of PMVs@Carvedilol may be a promising treatment for myocardial reperfusion injury, as it significantly improves postinjury cardiac function and increases drug utilization compared to other delivery methods.

Nrf2 Promotes Inflammation in Early Myocardial Ischemia-Reperfusion via Recruitment and Activation of Macrophages.

Cardiomyocyte apoptosis in response to inflammation is a primary cause of myocardial ischemia-reperfusion injury (IRI). Nuclear factor erythroid 2 like 2 (Nrf2) reportedly plays an important role in myocardial IRI, but the underlying mechanism remains obscure. Expression data from the normal heart tissues of mice or heart tissues treated with reperfusion for 6 h after ischemia (IR6h) were acquired from the GEO database; changes in biological function and infiltrating immune cells were analyzed. The binding between the molecules was verified by chromatin immunoprecipitation sequencing. Based on confirmation that early myocardial ischemia-reperfusion (myocardial ischemia/reperfusion for 6 hours, IR6h) promoted myocardial apoptosis and inflammatory response, we found that Nrf2, cooperating with Programmed Cell Death 4, promoted transcription initiation of C-C Motif Chemokine Ligand 3 (Ccl3) in myocardial tissues of mice treated with IR6h. Moreover, Ccl3 contributed to the high signature score of C-C motif chemokine receptor 1 (Ccr1)-positive macrophages. The high signature score of Ccr1-positive macrophages leads to the release of pro-inflammatory factors interleukin 1 beta and interleukin 6. This study is the first to elucidate the damaging effect of Nrf2 via remodeling of the immune microenvironment in early myocardial ischemia-reperfusion, which provides us with new perspectives and treatment strategies for myocardial ischemia-reperfusion.

RASSF9 promotes NSCLC cell proliferation by activating the MEK/ERK axis.

The RAS-associated domain family 9 (RASSF9), a RAS-associated domain family gene, is expressed in a variety of tissues. However, its roles in tumorigenesis, particularly in non-small cell lung cancer (NSCLC), are still not understood well. In the present study, we aimed to examine the potential roles of RASSF9 in NSCLC and the underlying mechanisms. Our data showed that RASSF9 expression was upregulated in NSCLC tissues and cell lines. Increased expression of RASSF9 promotes NSCLC cell proliferation. On the contrary, knockdown of RASSF9 represses cell proliferation. Moreover, the effects of RASSF9 on NSCLC cell proliferation were further confirmed in vivo by using a subcutaneous tumor model. Mechanistically, pharmacological intervention studies revealed that the MEK/ERK axis is targeted by RASSF9 for transducing its regulatory roles on NSCLC cell proliferation. Collectively, our data indicate that RASSF9 plays a key role in tumorigenesis of NSCLC by stimulating tumor cell proliferation, which relies on activation of the MEK/ERK axis. Thus, RASSF9 might be a druggable target for developing novel agents for treating NSCLC.

Effectiveness of photon-initiated photoacoustic streaming in root canal models with different diameters or tapers.

BACKGROUND: This study aimed to compare the use of photon-initiated photoacoustic streaming (PIPS) and conventional needle irrigation (CNI) in conjunction with different concentrations of sodium hypochlorite (NaOCl) to remove Enterococcus faecalis (E. faecalis) suspended bacteria and biofilms from root canal systems with different diameters or tapers. METHODS: Artificial root canal samples (n = 480) were randomly divided into three groups (n = 160/group). The canals were prepared to fit file sizes #10/.02, #25/.02, or #25/.06. The size #10/.02 group was incubated for seven days. The size #25/.02 or #25/.06 group was incubated for 2 days. A stable biological model of E. faecalis infection was established. The root canals were washed with distilled water or with 1%, 2%, or 5.25% NaOCl combined with CNI or PIPS. Bacterial suspensions and biofilms were assessed using an ATP assay kit and fluorescence microscopy. Image-Pro Plus was used to analyse the average fluorescence intensity to determine the most suitable root canal irrigation solution. RESULTS: In the CNI and PIPS groups, the ATP value of the 5.25% NaOCl subgroup was the lowest, followed by that of the 2% and 1% NaOCl subgroups. The ATP value of the distilled water subgroup was the highest (P < 0.05). When the root canal taper was 0.02, the ATP value of the #10/.02 + PIPS group was significantly lower than that of the #25/.02 + CNI group (P < 0.05). The average fluorescence intensity of the #10/.02 + PIPS group was lower than that of the #25/.02 + CNI group (P < 0.05). When the apical diameter was #25, the ATP value of the 0.02 taper in the PIPS group was lower than that of the 0.06 taper in the CNI group (P < 0.05), and the average fluorescence intensity of the 0.02 taper + PIPS group was lower than that of the 0.06 taper + CNI group (P < 0.05). PIPS combined with 2% and 5.25% NaOCl effectively improved the long-term antibacterial effect after irrigation and re-culture for 6 h. CONCLUSIONS: Compared with CNI, PIPS has greater ability to remove bacteria in root canals with a small preparation diameter and a small taper. PIPS with 2% and 5.25% NaOCl exhibited superior antibacterial and bacteriostatic effects.

The Emerging Role of Exosomes in Oral Squamous Cell Carcinoma.

Oral cancer constitutes approximately 2% of all cancers, while the most common type, oral squamous cell carcinoma (OSCC) represents 90% of oral cancers. Although the treatment of OSCC has improved recently, it still has a high rate of local recurrence and poor prognosis, with a 5-year survival rate of only 50%. Advanced stage OSCC tends to metastasize to lymph nodes. Thus, exploring new therapeutic strategies for OSCC is therefore an urgent priority. Exosomes, the small membrane vesicles derived from endosomes, have been detected in a wide array of bodily fluids. Exosomes contain a diversity of proteins, mRNAs, and non-coding RNAs, including microRNAs, long non-coding RNAs, piRNAs, circular RNAs, tsRNAs, and ribosomal RNAs, which are delivered to neighboring cells or even transported to distant sites. Exosomes have been associated with the tumorigenesis of OSCC, promote the proliferation, colonization, and metastasis of OSCC by transferring their contents to the target cells. Furthermore, exosomes are involved in the regulation of the tumor microenvironment to transform conditions favoring cancer progression in vivo. In this review, we summarize the crucial role of exosomes in the tumorigenesis and progression of OSCC and discuss the potential clinical application of exosomes in OSCC treatment.

Impacts of contracted endodontic cavities compared to traditional endodontic cavities in premolars.

BACKGROUND: This study aims to compare the percentage of dentin removed, instrumentation efficacy, root canal filling and load at fracture between contracted endodontic cavities, and traditional endodontic cavities on root canal therapy in premolars. METHODS: Forty extracted intact human first premolars were imaged with micro-CT and randomly assigned to the contracted endodontic cavity (CEC) or traditional endodontic cavity (TEC) groups. CEC was prepared with the aid of a 3D-printed template, canals were prepared with a 0.04 taper M-Two rotary instrument, and cavities were restored with resin. Specimens were loaded to fracture in an Instron Universal Testing Machine after a fatigue phase. The data were analyzed by the independent samples T test and Mann-Whitney U test, appropriate post hoc tests. RESULTS: In the premolars tested in vitro, the percentage of dentin removed in the premolars with two dental roots in the CEC group (3.85% ± 0.42%) was significantly smaller (P < 0.05) than in the TEC group (4.94% ± 0.5%). The untouched canal wall (UCW) after instrumentation for TECs (16.43% ± 6.56%) was significantly lower (P < .05) than the UCW (24.42% ± 9.19%) for CECs in single-rooted premolars. No significant differences were observed in the increased canal volume and surface areas in premolars between the TEC and CEC groups (P > 0.05). CECs conserved coronal dentin in premolars with two dental roots but no impact on the instrument efficacy. There were no differences between the CEC groups and the TEC groups in the percentage of filling material and voids (P > 0.05). In addition, the mean load at failure of premolars did not significantly differ between the CEC and TEC groups and there was no significant difference in the type of fracture (P > 0.05). CONCLUSION: The results of this study suggest that CEC could not improve the fracture resistance of the endodontically treated premolars. The instrumentation efficacy and the percentage of filling material did not significantly differ between CECs and TECs in premolars.

Mmu_circ_003795 regulates osteoblast differentiation and mineralization in MC3T3­E1 and MDPC23 by targeting COL15A1.

Circular RNAs (circRNAs) are a class of non­coding RNAs that exhibit important regulatory roles in various biological processes. However, the role of circRNAs and their potential role in osteoblast differentiation and mineralization is unclear. The aim of the present study was to investigate the expression of mmu_circ_003795 and its effect on collagen type XV α 1 chain (COL15A1). First, it was identified that the expression levels of mmu_circ_003795 and osteopontin (OPN) were upregulated in the induced cells. Silencing of mmu_circ_003795 reduced the gene and protein levels of COL15A1 and OPN, whereas the expression level of mmu­microRNA (miR)­1249­5p was upregulated. In addition, after 7 or 14 days of induction, alkaline phosphatase and Alizarin Red­S staining were decreased in the mmu_circRNA_003795 inhibitory group compared with the negative control group. In conclusion, mmu_circ_003795 may regulate osteoblast differentiation and mineralization in MC3T3­E1 and MDPC23 cells via mmu­miR­1249­5p by targeting COL15A1.

Chitosan/collagen scaffold containing bone morphogenetic protein-7 DNA supports dental pulp stem cell differentiation in vitro and in vivo.

In this study, porous chitosan/collagen scaffolds were prepared through a freeze-drying process, and loaded with the plasmid vector encoding human bone morphogenetic protein-7 (BMP-7) gene. To investigate the feasibility and efficacy of this gene-activated scaffold on dental tissue engineering, human dental pulp stem cells (DPSCs) were seeded in this scaffold for in vitro and in vivo study. In vitro results indicated that cells can be transfected successfully by loaded plasmid and secrete BMP-7 until day 24. Evaluation of DNA content, ALP activity, calcium content, SEM, and real-time PCR revealed that cells on gene-activated scaffold showed better proliferation properties and odontoblastic differentiation behaviors than cells on pure scaffolds. Then, these cell-scaffold complexes were implanted subcutaneously and retrieved after 4 weeks for histology evaluation. In vivo results that gene-activated scaffold group could still trace the existence of tranfected cells at week 4 and showed the upregulated expression of DSPP compared to pure scaffold groups. On the basis of our results, chitosan/collagen-loaded BMP-7 DNA appears to be an effective substrate candidate for gene delivery and indeed enhanced DPSCs differentiation toward an odontoblast-like phenotype in vitro and in vivo. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012.

Cardiac Sympathetic Denervation Suppresses Atrial Fibrillation and Blood Pressure in a Chronic Intermittent Hypoxia Rat Model of Obstructive Sleep Apnea.

Background Chronic intermittent hypoxia ( CIH ) is a distinct pathological mechanism of obstructive sleep apnea ( OSA ), which is recognized as an independent risk factor for cardiovascular diseases. The aims of this study were to ascertain whether CIH induces atrial fibrillation ( AF ), to determine whether cardiac sympathetic denervation ( CSD ) can prevent it and suppress blood pressure, and to explore the potential molecular mechanisms involved. Methods and Results Sixty Sprague-Dawley male rats were randomly divided into 4 groups: sham, CSD , CIH , CIH + CSD . The rats were exposed either to CIH 8 hours daily or normoxia for 6 weeks. Cardiac pathology and structure were analyzed by hematoxylin and eosin staining and echocardiogram. ECG, blood pressure, body weight, and blood gas were recorded. Connexin 43 and tyrosine hydroxylase were detected by western blot, immunohistochemistry, and immunofluorescence. CIH induced atrial remodeling, and increased AF inducibility. CSD treatment reduced postapneic blood pressure rises and AF susceptibility, which could attenuate CIH -associated structural atrial arrhythmogenic remodeling. In addition, CIH -induced sympathetic nerve hyperinnervation and CSD treatment reduced sympathetic innervation, which may affect CIH -induced AF -associated sympathovagal imbalance. Connexin 43 was specifically downregulated in CIH , whereas CSD treatment increased its expression. Conclusions These results suggested CIH induces atrial remodeling, increases AF inducibility, results in sympathetic nerve hyperinnervation, and decreases connexin 43 expression, but CSD treatment reduces AF susceptibility, postapneic blood pressure increase, sympathetic innervation, and the alteration of Cx43, which may be a key point in the genesis of CIH -induced AF .

Overexpression of filamin c in chronic intermittent hypoxia-induced cardiomyocyte apoptosis is a potential cardioprotective target for obstructive sleep apnea.

PURPOSE: Chronic intermittent hypoxia (CIH) is key pathological mechanism of obstructive sleep apnea (OSA), which induced cardiac dysfunction. Filamin c (FLNC) is a muscle-restricted isoform and predominantly expressed in muscle tissue. In this study, we utilized a recently developed CIH rat model to mimic OSA, investigated the expression of FLNC in cardiomyocytes, and examined the correlations of FLNC with active caspase-3 to ascertain whether FLNC regulates the survival of cardiomyocytes. METHODS: Forty Sprague-Dawley rats were randomly divided into normoxia and CIH groups. All rats were exposed either to normoxia or CIH 8 h daily for 6 weeks. Echocardiogram and HE staining were used to examine cardiac pathology, structure, and function. Body weight, heart weight, and blood gas values were recorded, respectively. The FLNC, Bax, Bcl-2, BNIP 3, and active caspase-3 proteins were detected by western blot; FLNC was examined by immunohistochemistry and immunofluorescence. Association of FLNC with cardiomyocyte apoptosis was detected by immunofluorescence. RESULTS: CIH induced cardiac injuries and caused arterial blood gas disorder. FLNC significantly increased in CIH-induced cardiomyocytes than that in normoxia tissues. Pro-apoptotic BNIP 3 and Bax proteins were significantly increased in CIH, whereas anti-apoptotic member Bcl-2 was decreased. Active caspase-3, a universal marker of apoptosis, was significantly increased in CIH group. Co-localizations of FLNC and active caspase-3 were observed in CIH group. CONCLUSIONS: These results suggested FLNC is implicated in the pathogenesis of CIH-induced cardiomyocyte apoptosis, and FLNC may serve as a novel cardioprotective target for OSA patients.

Research progress on the role and mechanism of miR-155 in the development of oral squamous cell carcinoma / 口腔疾病防治

@#Oral squamous cell carcinoma (OSCC) is the most common oral cancer. Previous studies have found significantly high miR-155 expression in OSCC. However, the mechanism by which miR-155 plays a role in OSCC oncogenesis is not yet clear. This article reviews the function of the relationship between miR-155 and tumors and the potential role of miR-155 in the development of OSCC. A literature review showed that mir-155, as a small carcinogenic RNA, can inhibit CDC73, BCL6, P27Kip1 and other target genes that play a role in cancer inhibition; promote the proliferation, migration and invasion of OSCC cells; and inhibit apoptosis. miR-155 can also be combined with biological factors (Epstein-Barr virus, human papillomavirus) to promote the development of OSCC.

Direct resin composite restoration of maxillary central incisors using a 3D-printed template: two clinical cases.

BACKGROUND: Three-dimensional (3D) printing technology is used widely in dentistry for applications including implant surgery, oral and maxillofacial surgery, orthognathic surgery, endodontics and prosthodontics. Using a 3D-printed template makes performing the repair procedure faster and more convenient. The aesthetic restoration of anterior teeth can recover facial beauty, enhance speaking and chewing functions and improve the quality of life of the patient. CASE PRESENTATION: This article describes two kinds of clinical cases including fractured teeth and dental caries. In both, a 3D-printed template was used for direct resin composite restoration of maxillary central incisors. A 3D-printed template was built using the following 3-step process: data acquisition was conducted via intra-oral scanning, virtual modeling was performed using an imaging process, and manufacturing was performed using a 3D printer. Aesthetically restoring the maxillary incisors with the assistance of the 3D-printed template achieved the anticipated results, and the patients were very satisfied with the effect. CONCLUSIONS: The direct resin composite restoration of maxillary central incisors using a 3D-printed template represents a rapid, convenient, aesthetic and functional option for treating maxillary central incisors. A 3D-printed template is therefore an acceptable and reliable alternative to traditional direct composite restoration of maxillary central incisors including fractured teeth and dental caries.

Biomechanical Properties of First Maxillary Molars with Different Endodontic Cavities: A Finite Element Analysis.

INTRODUCTION: The aim of this study was to compare the biomechanical properties of first maxillary molars with different endodontic cavities using the finite element method. METHODS: Three finite element analysis models of a maxillary first molar were designed and constructed with 3 different types of endodontic cavities: a traditional endodontic cavity, a conservative endodontic cavity, and an extended endodontic cavity. An intact tooth model was used for comparison. Each model was subjected to 3 different force loads directed at the occlusal surface. The stress distribution patterns and the maximum von Mises (VM) stresses were calculated and compared. RESULTS: The peak VM stress on all models was at the site of the force load. The occlusal stresses were spread in an approximate actinomorphic pattern from the force loading point, and the stress was much higher when the force load was close to the access cavity margin. The peak root VM stresses on the root-filled teeth occurred at the apex and were significantly higher than that on the intact tooth, which appeared on the pericervical dentin. The area of pericervical dentin experiencing high VM stress increased as the cavities extended and the stress became concentrated in the area between the filling materials and the dentin. CONCLUSIONS: The stress distribution on the occlusal surface were similar between the conservative endodontic cavity, the traditional endodontic cavity, and the extended endodontic cavity. With enlargement of the access cavity, the stress on the pericervical dentin increases dramatically.

A novel method for periapical microsurgery with the aid of 3D technology: a case report.

BACKGROUND: Three-dimensional (3D) technology has gained wide acceptance in dentistry. It has been used for treatment planning and surgical guidance. This case report presented a novel treatment approach to remove cortical bone and root-end during periapical surgery with the help of Cone-Beam Computed Tomography (CBCT), Computer Aided Design (CAD) and three-dimensional (3D) printing technology. CASE PRESENTATION: A 37-year-old female patient presented with a large periapical lesion of left maxillary lateral incisor and canine was referred for microsurgical endodontic surgery. The data acquired from a preoperative diagnostic CBCT scan and an intra-oral scan was uploaded into surgical planning software and matched. A template that could be used to locate root-ends and lesion areas was virtually designed based on the data and was fabricated using a 3D printer. With the guidance of the template, the overlying cortical bone and root-end were precisely removed by utilizing a trephine with an external diameter of 4.0 mm. The patient was clinically asymptomatic at a six-month follow-up review. One year after the surgery, the lesion was healing well and no periapical radiolucency was observed on radiographic examination. CONCLUSIONS: The digitally designed directional template worked in all aspects to facilitate the periapical surgery as anticipated. The root-ends were accurately located and resected. The surgical procedure was simplified, and the treatment efficiency was improved. This technique minimized the damage and reduced iatrogenic injury.

Novel navigation technique for the endodontic treatment of a molar with pulp canal calcification and apical pathology.

Apical periodontitis, the inflammation of periapical tissue, commonly requires root canal treatment to achieve apical healing. However, if it is accompanied by pulp canal calcification, the treatment becomes complicated, and locating the root canal can be challenging. This case report describes a novel approach for treating a molar with pulp canal calcification and apical pathology. Due to the risk of perforation during treatment, a digitally printed template was used to assist in accurately locating the root canal. After six months, the patient was asymptomatic and the periradicular radiolucency was gradually reducing in size.