Aims
To use experimental periodontitis models in rats to investigate the correlation between local expression of the complement components C3b and C4b in periodontal tissues and disease severity, and ...to assess the therapeutic effects of targeting C3b/C4b on inflammatory bone loss.
Materials and Methods
The gingival expression of C3, C3b, and C4b in animal experimental periodontitis models were analysed immunohistochemically. The therapeutic effects of the C3b/C4b inhibitor (SB002) on ligation‐induced experimental periodontitis was examined using biochemical, histological, and immunohistochemical analyses.
Results
The gingival expression levels of C3, C3b, and C4b were positively correlated with the severity of periodontitis. Moreover, both single and multiple injections of the C3b/C4b inhibitor had preventive and therapeutic effects on alveolar bone loss in ligation‐induced experimental periodontitis with no associated adverse consequences.
Conclusions
The association between C3b/C4b and periodontitis may provide a basis for the development of novel therapeutic strategies for periodontitis and other inflammatory diseases.
The impact of the pandemic of COVID-19 has a certain influence on various walks of life around the world. Because of the pandemic of this novel coronavirus in terms of COVID-19, the social life ...global wide has been changed a lot. To keep the social distance between human being to prevent from being infected is the most important strategy for all the countries. Many dental schools have been locked down to minimize the spread out of this coronavirus infection. Close contact between human being are required for all those learning process in traditional dental education. Learning methods should be innovated to keep on the learning process but away from being infected for dental education during pandemic. The purpose of this manuscript is to exchange the information and experience of those dental educators from different countries to prepare for the future demand for dental education during pandemic.
By means of three online symposiums, dental educators from different countries were invited to give presentation and discussion regarding to the information and experience in the innovation of dental education during the pandemic.
The results showed that the impact of the pandemic of COVID-19 affects the dental education a lot. Intelligent technology has certain benefit for the learning process of dental education during the pandemic.
The impact of the pandemic of COVID-19 affects dental education a lot. The model of dental education should be innovated to suit different situations and novelty intelligent technology should be applied for future dental education.
A 3D printed model includes a tooth body, pulp cavity, and root canal system is useful in simulating clinical condition.The 3D printing method and Cone-Beam Computed Tomography (CBCT) image to create ...a tooth model that can be applied to various different dental training manikin.
We used 3D printing to fabricate teeth obtained from CBCT image. Being installed into the model, a conductive wire was placed at the apex of the root tip where filled with solution. On the other side, a connective probe wire extended to the cheek of the human head model and was then connected with the lip hock of the electronic apex locator to form a circuit. When the probe of the electronic apex locator approaches the apex, an audible sound is produced. A bee-bee warning sound was emitted as the probe passes through the apical foramen. Therefore, the devices can simulate the actual conditions during clinical root canal treatment.
This device can be applied in preclinical dental student root canal therapy training, objective structured clinical examination (OSCE), endodontic specialist training and standardized training procedures. This may also integrate with dental simulation systems and develop a new training programs in dental simulation system to help our biomedical industry develop distinctive products and enhance international competitiveness.
This model can be conveniently attached onto the dental training manikin at preclinical dental laboratory training in dental schools.
•Down-regulation of CISH in OSCC tissues and cell lines.•CISH mediates cellular functions through STAT3 inhibition.•MiR-944 regulates cellular functions through direct binding of CISH.•Cigarette ...smoking-mediated miR-944/CISH/STAT3 axis plays a role in oral carcinogenesis.
The cytokine-inducible Src homology 2-containing protein (CISH) is an endogenous suppressors of signal transduction and activator of transcription (STAT) and acts as a key negative regulator of inflammatory cytokine responses. Downregulation of CISH has been reported to associate with increased activation of STAT and enhanced inflammatory pathways. However, whether microRNAs (miRNAs) play a crucial role in CISH/STAT regulation in oral squamous cell carcinoma (OSCC) remains unknown. The expression of CISH on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-944 and CISH were accessed by transwell migration and invasion analyses using gain- and loss-of-function approaches. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were used to evaluate the pro-inflammation cytokines expression under the miR-944, CISH, NNK or combinations treatment. We found that the CISH protein, which modulates STAT3 activity, as a direct target of miR-944. CISH protein was significantly down-regulated in OSCC patients and cell lines and its level was inversely correlated with miR-944 expression. The miR-944-induced STAT3 phosphorylation, pro-inflammation cytokines secretion, migration and invasion were abolished by CISH restoration, suggesting that the oncogenic activity of miR-944 is CISH dependent. Furthermore, tobacco extract (NNK) may contribute to miR-944 induction and STAT3 activation. Antagomir-mediated inactivation of miR-944 prevented the NNK-induced STAT3 phosphorylation and pro-inflammation cytokines secretion. Altogether, these data demonstrate that NNK-induced miR944 expression plays an important role in CISH/STAT3-mediated inflammatory response and activation of tumor malignancy.
microRNA (miRNA) dysregulation contributes widely to human cancer but has not been fully assessed in oral cancers. In this study, we conducted a global microarray analysis of miRNA expression in 40 ...pairs of betel quid-associated oral squamous cell carcinoma (OSCC) specimens and their matched nontumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared with the matched tissue. Among these downregulated miRNAs, 19 miRNAs were found and mapped to the chromosome 14q32.2 miRNA cluster region, which resides within a parentally imprinted region designated as Dlk-Dio3 and known to be important in development and growth. Bioinformatic analysis predicted two miRNAs from the cluster region, miR329 and miR410, which could potentially target Wnt-7b, an activator of the Wnt-β-catenin pathway, thereby attenuating the Wnt-β-catenin signaling pathway in OSCC. Stable ectopic expression of Wnt-7b in OSCC cells overexpressing miR329 or miR410 restored proliferation and invasion capabilities abolished by these miRNA. Combining a demethylation agent and a histone deacetylase inhibitor was sufficient to reexpress miR329, miR410, and Meg3, consistent with epigenetic regulation of these miRNA in human OSCC. Specifically, arecoline, a major betel nut alkaloid, reduced miR329, miR410, and Meg3 gene expression. Overall, our results provide novel molecular insights into how betel quid contributes to oral carcinogenesis through epigenetic silencing of tumor-suppressor miRNA that targets Wnt-β-catenin signaling.
Maxillary protraction with or without expansion is a widely known orthopedic treatment modality in growing skeletal Class III patients. However, limited data are available regarding the outcomes of ...long-term changes in the maxilla. Aim of this meta-analysis was to assess the effectiveness of the long-term maxillary anteroposterior changes following a facemask therapy with or without rapid maxillary expansion in growing skeletal Class III patients.
A comprehensive literature search was conducted using the databases of PubMed, Science Direct, Web of Science, and Embase. Randomized controlled trials and cohort studies, published up to Sep. 2020, with maxillary protraction and/or expansion as keywords were included in this meta-analysis. Risk of bias within and across studies were assessed using the Cochrane tools (RoB2.0 and ROBINS-I) and GRADE approach. Overall and subgroup comparisons with the random-effect model were performed in this meta-analysis. Meta-regression models were designed to determine potential heterogeneity.
There was a statistically significant increase (Mean difference, 2.29°; 95% confidence interval, 1.86-2.73; and p < 0.001 after facemask (FM) protraction. Mean difference, 1.73°; 95% confidence interval, 1.36-2.11; and p < 0.001 after rapid maxillary expansion(RME) and facemask protraction) in the Sella-Nasion-A point (SNA) angle in the treatment groups as compared with the control groups, when measured during the less than 3-year follow-up period. However, no statistically significant changes (Mean difference, 0.28°; 95% confidence interval, -0.57-1.13; and p = 0.52 after facemask protraction. Mean difference, 0.34°; 95% confidence interval, -0.64-1.33; and p = 0.50 after rapid maxillary expansion and facemask protraction) were observed in the SNA angle in the groups, when measured after 3 years of follow-up. Meta-regression analysis also showed that with increased follow-up duration, the effectiveness of maxillary protraction decreased.
This meta-analysis revealed that maxillary protraction therapy could be effective for a short-term in correcting maxillary hypoplasia and the treatment result was not affected by mean age and sex. However, with increased follow-up duration, the sagittal maxillary changes gradually decreased. Limitations on this review were only the SNA angle was used and clinical heterogeneity was not discussed. The quality of evidence was moderate. Further long-term observational studies are necessary for a comprehensive evaluation of the effects on maxillary skeletal changes.
Background
Silibinin has shown various pharmacological effects that could be attributed to its antioxidant, anti‐inflammatory, and immunoregulatory properties. However, the therapeutic potential of ...silibinin for periodontitis has not been investigated.
Methods
The therapeutic effects of silibinin in ligation‐induced experimental periodontitis were investigated using biochemical, histological, and immunohistochemical methods. The effects of silibinin on the osteoclastogenesis of RAW264.7 cells were investigated using TRAP staining, quantitative polymerase chain reaction (qPCR), pit formation, and immunoblotting. Moreover, its effects on inflammatory cytokine production, RANKL expression, and oxidative stress in lipopolysaccharide (LPS)‐stimulated human gingival fibroblasts (HGFs) were evaluated using qPCR and flow cytometry. A coculture system was established to elucidate the effects of silibinin on the crosstalk between LPS‐stimulated HGFs and undifferentiated monocytes.
Results
Silibinin significantly reduced the alveolar bone loss, decreased the gingival inflammation and RANKL expression, and decreased the RANKL/osteoprotegerin ratio in gingival tissues in experimental periodontitis. The in vitro results showed that silibinin inhibited RANKL‐induced osteoclast differentiation and function of RAW264.7 cells and suppressed RANKL‐induced nuclear factor of activated T cells 1 (NFATc1) induction and translocation through the nuclear factor‐κB and mitogen‐activated protein kinase signaling pathways. Silibinin decreased the inflammatory cytokine level and oxidative stress production in LPS‐stimulated HGFs; significantly suppressed membrane‐bound RANKL expression on LPS‐stimulated HGFs; and significantly disrupted TRAP+ cell differentiation in the coculture system.
Conclusions
Silibinin effectively inhibits inflammation‐induced bone loss in experimental periodontitis based on the regulation of stimulated HGFs by inhibiting the expression of inflammatory and osteoclastogenic mediators. Collectively, targeting the inflamed HGF resolution that mediates osteogenesis may use silibinin as a potential drug‐repurposing candidate for modulating alveolar bone destruction in periodontitis.
Summary
Silibinin effectively inhibits inflammation‐induced bone loss in experimental periodontitis based on the regulation of stimulated HGFs by inhibiting the expression of inflammatory and osteoclastogenic mediators.
Background
This study aimed to investigate the contribution of myeloid differentiation primary‐response gene 88 (MyD88) on the differentiation of T helper type 17 (Th17) and regulatory T (Treg) cells ...and the emerging subgingival microbiota dysbiosis in Porphyromonas gingivalis‐induced experimental periodontitis.
Methods
Alveolar bone loss, infiltrated inflammatory cells, immunostained cells for tartrate‐resistant acid phosphatase (TRAP), the receptor activator of nuclear factor‐kB ligand (RANKL), and osteoprotegerin (OPG) were quantified by microcomputerized tomography and histological staining between age‐ and sex‐matched homozygous littermates (wild‐type WT, Myd88+/+ and Myd88−/− on C57BL/6 background). The frequencies of Th17 and Treg cells in cervical lymph nodes (CLNs) and spleen were determined by flow cytometry. Cytokine expression in gingival tissues, CLNs, and spleens were studied by quantitative polymerase chain reaction (qPCR). Analysis of the composition of the subgingival microbiome and functional annotation of prokaryotic taxa (FAPROTAX) analysis were performed.
Results
P. gingivalis‐infected Myd88−/− mice showed alleviated bone loss, TRAP+ osteoclasts, and RANKL/OPG ratio compared to WT mice. A significantly higher percentage of Foxp3+CD4+ T cells in infected Myd88−/− CLNs and a higher frequency of RORγt+CD4+ T cells in infected WT mice was noted. Increased IL‐10 and IL‐17a expressions in gingival tissue at D14–D28 then declined in WT mice, whereas an opposite pattern was observed in Myd88−/− mice. The Myd88−/− mice exhibited characteristic increases in gram‐positive species and species having probiotic properties, while gram‐negative, anaerobic species were noted in WT mice. FAPROTAX analysis revealed increased aerobic chemoheterotrophy in Myd88−/− mice, whereas anaerobic chemoheterotrophy was noted in WT mice after P. gingivalis infection.
Conclusions
MyD88 plays an important role in inflammation‐induced bone loss by modulating the dynamic equilibrium between Th17/Treg cells and dysbiosis in P. gingivalis‐induced experimental periodontitis.
Increasing evidence suggests that high glucose (HG) causes abnormalities in endothelial and vascular smooth muscle cell function (VSMC) and contributes to atherosclerosis. Receptor for advanced ...glycation end-products (RAGE) has been linked to the pathogenesis of both the macrovascular and microvascular complications of diabetes. Cilostazol is used to treat diabetic vasculopathy by ameliorating HG-induced vascular dysfunction.
In this study, we investigated whether the cilostazol suppression of HG-induced VSMC dysfunction is through RAGE signaling and its possible regulation mechanism.
We investigated the effect of HG and cilostazol on RAGE signaling in A7r5 rat VSMCs. Aortic tissues of streptozotocin (STZ) diabetic mice were also collected.
Aortic tissue samples from the diabetic mice exhibited a significantly decreased RAGE expression after cilostazol treatment. HG increased RAGE, focal adhesion kinase (FAK), matrix metalloproteinase-2 (MMP-2), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions, and was accompanied with increased reactive oxygen species (ROS), cell proliferation, adhesion and migration. Cilostazol significantly reversed HG-induced RAGE, ROS, downstream gene expressions and cell functions. RAGE knockdown significantly reversed the expressions of HG-induced vasculopathy related gene expressions and cell functions. Cilostazol with RAGE knockdown had additive effects on downstream ERK/NF-κB signaling pathways, gene expressions and cell functions of A7r5 rat VSMCs in HG culture.
Both in vitro and in vivo experimental diabetes models showed novel signal transduction of cilostazol-mediated protection against HG-related VSMC dysfunction, and highlighted the involvement of RAGE signaling and downstream pathways.
Accumulating evidence is indicating metformin to possess the potential ability in preventing tumor development and suppressing cancer growth. However, the exact mechanism of its antitumorigenic ...effects is still not clear. We found that metformin suppressed the ability of cancer to skew macrophage toward M2 phenotype. Metformin treated cancer cells increased macrophage expression of M1-related cytokines IL-12 and TNF-α and attenuated M2-related cytokines IL-8, IL-10, and TGF-β expression. Furthermore, metformin treated cancer cells displayed inhibited secretion of IL-4, IL-10 and IL-13; cytokines important for inducing M2 macrophages. Conversely, M1 inducing cytokine IFN-γ was upper-regulated in cancer cells. Additionally, through increasing AMPK and p65 phosphorylation, metformin treatment activated AMPK-NF-κB signaling of cancer cells that participate in regulating M1 and M2 inducing cytokines expression. Moreover, Compound C, an AMPK inhibitor, significantly increased IL-4, IL-10, and IL-13 expression while BAY-117082, an NF-κB inhibitor, decreased expression. In metformin-treated tumor tissue, the percentage of M2-like macrophages decreased while M1-like macrophages increased. These findings suggest that metformin activates cancer AMPK-NF-κB signaling, a pathway involved in regulating M1/M2 expression and inducing genes for macrophage polarization to anti-tumor phenotype.
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