Immune-related signature of periodontitis and Alzheimer's disease linkage.

Background: Periodontits (PD) and Alzheimer's disease (AD) are both associated with ageing and clinical studies increasingly evidence their association. However, specific mechanisms underlying this association remain undeciphered, and immune-related processes are purported to play a signifcant role. The accrual of publicly available transcriptomic datasets permits secondary analysis and the application of data-mining and bioinformatic tools for biological discovery. Aim: The present study aimed to leverage publicly available transcriptomic datasets and databases, and apply a series of bioinformatic analysis to identify a robust signature of immune-related signature of PD and AD linkage. Methods: We downloaded gene-expresssion data pertaining PD and AD and identified crosstalk genes. We constructed a protein-protein network analysis, applied immune cell enrichment analysis, and predicted crosstalk immune-related genes and infiltrating immune cells. Next, we applied consisent cluster analysis and performed immune cell bias analysis, followed by LASSO regression to select biomarker immune-related genes. Results: The results showed a 3 gene set comprising of DUSP14, F13A1 and SELE as a robust immune-related signature. Macrophages M2 and NKT, B-cells, CD4+ memory T-cells and CD8+ naive T-cells emerged as key immune cells linking PD with AD. Conclusion: Candidate immune-related biomarker genes and immune cells central to the assocation of PD with AD were identified, and merit investigation in experimental and clinical research.

Strong-field THz radiation-induced curing of composite resin materials in dentistry.

Dental caries is listed as one of the three major non-communicable diseases by the World Health Organization, and its main treatment method is to restore it by filling it with resin. At present, the visible light-cure method has the problems of non-uniform curing and low penetration efficiency, which makes the bonding area easy to develop marginal leakages, thus leading to secondary caries and requiring repeated treatment. In this work, through the strong terahertz (THz) irradiation-weak THz detection technique, it is found that the strong THz electromagnetic pulses can accelerate the curing process of the resin, and the weak-field THz spectroscopy can be used to monitor this dynamic change in real time, which will greatly promote the potential application of THz technology in dentistry.

GAS5 alleviates cisplatin drug resistance in oral squamous cell carcinoma by sponging miR-196a.

OBJECTIVE: The long non-coding RNA Growth-arrest-specific transcript 5 (GAS5) has been extensively linked with the ability of cancer cells to resist chemotherapeutic interventions. This prospective study aimed to investigate the role of GAS5 in oral squamous cell carcinoma (OSCC), which has been poorly characterized to date. METHODS: GAS5 and miR-196a expression levels were detected by quantitative real-time PCR analysis. Cisplatin (DDP) sensitivity and apoptosis levels were determined using Cell Counting Kit 8 and flow cytometry, respectively. Luciferase reporter and RNA immunoprecipitation assays were performed to confirm target miRNAs of GAS5. RESULTS: We found that GAS5 was expressed at low levels in DDP-resistant OSCC cell lines and tissues, and that GAS5 levels were intricately linked to the survival rates of OSCC patients. GAS5 overexpression led to the recovery of DDP sensitivity in CAL27/DDP cells. Additionally, in both DDP-resistant and -sensitive lines, GAS5 showed a cytoplasmic distribution and downregulated miR-196a in OSCC tissues. Exogenous transfection of miR-196a alleviated the effects of GAS5 on DDP sensitivity, confirming this as the mechanism of chemoresistance. CONCLUSIONS: These findings may provide new targets for the treatment of chemotherapy-resistant OSCC.

Dental caries diagnosis using terahertz spectroscopy and birefringence.

Dental caries is a widespread chronic infectious disease which may induce a series of oral and general problems if untreated. As a result, early diagnosis and follow-up following radiation-free dental caries therapy are critical. Terahertz (THz) waves with highly penetrating and non-ionizing properties are ideally suited for dental caries diagnosis, however related research in this area is still in its infancy. Here, we successfully observe the existence of THz birefringence phenomenon in enamel and demonstrate the feasibility of utilizing THz spectroscopy and birefringence to realize caries diagnosis. By comparing THz responses between healthy teeth and caries, the transmitted THz signals in caries are evidently reduced. Concomitantly, the THz birefringence is also unambiguously inhibited when caries occurs due to the destruction of the internal hydroxyapatite crystal structure. This THz anisotropic activity is position-dependent, which can be qualitatively understood by optical microscopic imaging of dental structures. To increase the accuracy of THz technology in detecting dental caries and stimulate the development of THz caries instruments, the presence of significant THz birefringence effect induced anisotropy in enamel, in combination with the strong THz attenuation at the caries, may be used as a new tool for caries diagnosis.

Shared Molecular Mechanisms between Alzheimer's Disease and Periodontitis Revealed by Transcriptomic Analysis.

OBJECTIVE: To investigate the genetic crosstalk mechanisms that link periodontitis and Alzheimer's disease (AD). BACKGROUND: Periodontitis, a common oral infectious disease, is associated with Alzheimer's disease (AD) and considered a putative contributory factor to its progression. However, a comprehensive investigation of potential shared genetic mechanisms between these diseases has not yet been reported. METHODS: Gene expression datasets related to periodontitis were downloaded from the Gene Expression Omnibus (GEO) database, and differential expression analysis was performed to identify differentially expressed genes (DEGs). Genes associated with AD were downloaded from the DisGeNET database. Overlapping genes among the DEGs in periodontitis and the AD-related genes were defined as crosstalk genes between periodontitis and AD. The Boruta algorithm was applied to perform feature selection from these crosstalk genes, and representative crosstalk genes were thus obtained. In addition, a support vector machine (SVM) model was constructed by using the scikit-learn algorithm in Python. Next, the crosstalk gene-TF network and crosstalk gene-DEP (differentially expressed pathway) network were each constructed. As a final step, shared genes among the crosstalk genes and periodontitis-related genes in DisGeNET were identified and denoted as the core crosstalk genes. RESULTS: Four datasets (GSE23586, GSE16134, GSE10334, and GSE79705) pertaining to periodontitis were included in the analysis. A total of 48 representative crosstalk genes were identified by using the Boruta algorithm. Three TFs (FOS, MEF2C, and USF2) and several pathways (i.e., JAK-STAT, MAPK, NF-kappa B, and natural killer cell-mediated cytotoxicity) were identified as regulators of these crosstalk genes. Among these 48 crosstalk genes and the chronic periodontitis-related genes in DisGeNET, C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3 were shared and identified as the most pivotal candidate links between periodontitis and AD. CONCLUSIONS: Exploration of available transcriptomic datasets revealed C4A, C4B, CXCL12, FCGR3A, IL1B, and MMP3 as the top candidate molecular linkage genes between periodontitis and AD.

Comparison of Postoperative Outcomes Between Envelope and Triangular Flaps After Mandibular Third Molar Surgery: A Systematic Review and Meta-Analysis.

PURPOSE: The objective of the present systematic review was to compare the postoperative outcomes between envelope and triangular flaps after mandibular third molar surgery. MATERIALS AND METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched from the inception date to November 2018. Randomized and nonrandomized controlled trials were included if they had met certain inclusion and exclusion criteria. The predictor variable was the flap design, envelope or triangular. The outcome variables were operation time, pain, trismus, alveolar osteitis (AO) incidence, wound dehiscence, and swelling. The methodologic quality assessment was performed in accordance with the Cochrane Collaboration guidelines. The meta-analysis was performed using Review Manager, version 5.2. RESULTS: A total of 21 studies were included for qualitative synthesis, 18 of which were included in the meta-analysis. The use of envelope flaps required less operation time than triangular flaps (P < .00001; I2 = 9%). In the Pell and Gregory A and B subgroups, envelope flaps were associated with a significantly lower visual analog scale score at 3 (P = .05, I2 = 0%) and 7 (P = .02; I2 = 0%) postoperative days and with a greater postoperative interincisal distance at 7 postoperative days (P = .04; I2 = 0%). In contrast, envelope flaps were associated with a greater AO incidence in the subgroup of split-mouth randomized controlled trials (P = .001; I2 = 0%). CONCLUSIONS: Envelope flaps required a shorter operation time than triangular flaps and were associated with less postoperative pain and trismus when applied to impacted mandibular third molars of Pell and Gregory Class A or B. In contrast, triangular flaps were associated with a decreased incidence of AO compared with envelope flaps.

[Local injection of exogenous nerve growth factor improves early bone maturation of implants].

OBJECTIVE: To investigate the effects of nerve growth factor (NGF) in the osteogenic action of implants and the maturation and reconstruction changes in bone tissues in the early stage of osseointegration. METHODS: The mouse implant model was established by placing titanium in the femoral head of the mouse and locally injecting NGF in the implant zone. On 1, 2 and 4 weeks after operation, stain samples were collected from animals using hematoxylin-eosin (HE) staining and Masson staining. The effect of NGF on the bone maturation was compared at different time points of early stage osseointegration. RESULTS: The results of HE and Masson staining indicated that the local injection of external NGF can up-regulate bone mass, amount of bone trabecula, and bone maturity in the mouse model. The mature bone rate in treatment group of 1 week and 4 weeks after operation were significantly higher than those in the control group (P<0.05). CONCLUSIONS: NGF can shorten the period of bone maturation.

Effects of vascular endothelial growth factor on osteoblasts around dental implants in vitro and in vivo.

Vasculogenesis is a pivotal procedure during dental implant osseointegration and bone repair process. Vascular endothelial growth factor (VEGF), regarded as one of the most important vasculogenesis factor, also plays a central role in bone repair, but its role around dental implants is still unknown. In the present study, rat primary osteoblasts seeded on titanium discs were tested using proliferation, enzyme-linked immunosorbent assay, Real-time PCR, and alkaline phosphatase (ALP) expression. Chicken embryo chorioallantoic membrane (CAM) was used to test the vasculogenesis property. In vivo VEGF-coated implants assay was used to test the osteocalcin (OCN)- and CD31-positive cells around an implant. VEGF could significantly promote osteoblasts seeded on titanium surfaces proliferation and secretion of VEGF protein (P < 0.05); increasing of VEGF, VEGFR1, VEGFR2, NRP-1, ALP and Runx2 mRNA expression (P < 0.05); up-regulating ALP expression on days 7 and 11 (P < 0.01). Supernatant of VEGF-induced osteoblasts could promote CAM vasculogenesis (P < 0.05). In vivo, VEGF-coated implants could promote OCN- and CD31-positive cells around bone lacunas. The present study shows that VEGF could induce primary rat osteoblasts proliferation, VEGF protein secretion, ALP expression, and VEGF-related mRNA expression in vitro. Osteoblasts co-cultured with VEGF could promote neovascularization in chicken embryos. In the in vivo experiments, coating the implant with VEGF could promote osteoblasts and endothelial cell expression.

Age-dependent impact of inferior alveolar nerve transection on mandibular bone metabolism and the underlying mechanisms.

Aging is associated with peripheral nerve degradation and bone destruction. The aim of the study is to elucidate the influence of sensory denervation on bone metabolism in different age groups by establishing a modified unilateral inferior alveolar nerve transection (IANT) model. The rats, divided into young, middle-aged and aged group, were sacrificed at 1, 2, 4 and 8 weeks after right IANT. The histological changes of mandibles were analyzed by fluorescent double labeling, micro-CT, HE, TRAP and anti-CGRP immunohistochemical staining. Molecular mechanisms underlying the changes were analyzed by qPCR and western blot. Differences between the test and control side were evaluated by paired-samples t test. The Friedman test and separate Wilcoxon signed-rank tests were applied to analyze age-dependent difference. The impact of IANT was the most intensive in developing bone, the most persistent in full grown bone and the faintest in the aged bone. The role of IAN in keeping homeostasis was closely related to the anabolic effect of CGRP, which suppressed the number of osteoclasts through OPG/RANKL ratio and controlled growth factors expression like BMP2. This study contributes to a better understanding of the molecular mechanisms of CGRP in vivo and the relationship among sensory nerve, bone metabolism and aging.

Effect of Increasing Doses of γ-Radiation on Bone Marrow Stromal Cells Grown on Smooth and Rough Titanium Surfaces.

Radiation therapy for oral and maxillofacial tumors could damage bone marrow stromal cells (BMSCs) in jaw, which caused dental implant failure. However, how radiation affects BMSCs on SLA (sandblasted with large-grits, acid-etched) surfaces is still unknown. The aim of this study was to investigate effect of different dose of γ-radiation on BMSCs on SLA and PT (polished titanium) surfaces. Rat BMSCs were radiated with 2, 4, and 8 Gy γ-radiation and then seeded on both surfaces. Cell adhesion, spreading, and proliferation were tested. The osteogenesis and the adipogenesis ability were examined by Alizarin-Red and Oil-Red staining, respectively. Real-time PCR was performed to detect osteogenic (osteocalcin, OCN; runt-related transcription factor 2, Runx2) and adipogenic (peroxisome proliferator-activated receptor gamma, PPARγ) gene expression at days 7 and 14 postirradiation. Results showed that γ-radiation reduced cell proliferation, adhesion, spreading, and osteogenic differentiation. 2 Gy radiation promoted adipogenic differentiation, but it was significantly decreased when dosage reached 4 Gy. In conclusion, results suggest that γ-radiation influenced BMSCs behaviors in a dosage-dependent manner except adipogenic differentiation, low dose promoted it, and high dose inhibited it. This effect was influenced by surface characteristics, which may explain the different failure rate of various implants in patients after radiation.