Correction: The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation.

[This corrects the article DOI: 10.1371/journal.ppat.1008093.].

Human bone marrow mesenchymal stem cell-derived extracellular vesicles restore Th17/Treg homeostasis in periodontitis via miR-1246.

T-cell-mediated immunity is crucial in the immunopathology of periodontitis. The restoration of the homeostasis between the T helper cell 17 (Th17) and regulatory T cell (Treg) subsets by extracellular vesicles (EVs) obtained from human bone marrow stem cells (hBMSCs) promotes new bone formation and suppresses inflammation. Uncovering the functions of hBMSC-derived EVs in the immune microenvironment of periodontal tissue and their underlying regulatory mechanisms may shed new light on developing potential cell-free immunotherapies for periodontal regeneration. Here, we reported that the Th17/Treg ratio elevated in peripheral blood from periodontitis patients. Furthermore, we found that hBMSC-derived EVs could reduce the Th17/Treg ratio in CD4+ T cells from periodontitis patients in vitro and ameliorate conditions of experimental periodontitis in mice. Additionally, by investigating the differentially expressed miRNAs and target genes in EVs from hBMSCs stimulated with Porphyromonas gingivalis LPS using miRNA sequencing, we found that EV-miR-1246 is highly effective at downregulating the ratio of Th17/Treg in vitro. Mechanistically, EV-miR-1246 suppressed expression of its potential target angiotensin-converting enzyme 2 (ACE2) and increased the p-Yes-associated protein (YAP)1/YAP1 ratio in CD4+ T cells. Our results indicated that hBMSC-derived EVs improve periodontitis via miR-1246, consequently downregulating Th17/Treg ratio, and represented a promising therapeutic target for precision treatment in periodontitis.

Performance improvement of underwater LIBS qualitative and quantitative analysis by irradiating with long nanosecond pulses.

Long nanosecond pulses have been proven to be efficient at enhancing underwater LIBS emission. However, the quantitative analytical capability of underwater long-pulse LIBS has yet to be further revealed. In this work, we investigated the spectral characteristics by irradiating with a laser pulse of 120 ns duration. The alkali and alkaline earth metals Li, K and Ca and the transition element Mn were selected for analysis. It is shown that obvious self-reversal structures were observed in the spectra at high concentrations, making the calibration curves saturated. Correction was performed using the approximate Voigt function fitting method, which significantly improves the linearity of the calibration curves. In addition to the target metal elements, atomic lines of the matrix elements H and O in water were also observed, which can serve as promising internal standards for quantitative analysis. A comparison of the quantification performance with and without the internal standards demonstrates that the use of the internal standards is conducive to improving the robustness of the calibration approaches with higher determination coefficients. More importantly, the underwater LIBS signal stability is improved by more than 3 times, and the prediction error for validation samples is reduced by 2-4 times. The present results suggest that long ns pulses are favorable to significantly improving the qualitative and quantitative performance of underwater single-pulse LIBS, enabling long-pulse LIBS to have great potential to be applied to underwater in situ chemical analysis.

Boundary of mandibular molar distalization in orthodontic treatment: A systematic review and meta-analysis.

To explore the mandibular retromolar space length (MRSL), initial root-inner cortex contact percentage (IRCCP), and the various factors that influence mandibular molar distalization. Searches were undertaken in PubMed, EMBASE, Web of Science, Cochrane Library, Scopus, and grey literature (Google Scholar and OpenGrey) for eligible cross-sectional observational studies measuring the MRSL and IRCCP in healthy adult patients. The risk of bias and evidence quality were evaluated using the Joanna Briggs Institute's checklist and GRADE framework. Thirteen studies involving 1169 patients were included for qualitative synthesis. Seven of these studies were eligible for quantitative analysis. Meta-analysis showed that the mean MRSL at the subfurcation-6 mm plane in Asian normodivergent cases was 3.78 mm (95% confidence interval [CI]: 2.81-4.35; I2 = 79.7%) for skeletal Class-I malocclusions, 3.02 mm (95% CI: 2.10-3.94; I2 = 62.5%) for Class-II, and 4.43 mm (95% CI: 3.14-5.73; I2 = 75.1%) for Class-III. The mean MRSL at the sub-cementoenamel junction (CEJ)-10 mm plane for Asian, Class-I, normodivergent cases was 3.28 mm (95% CI: 2.44-4.12; I2 = 68.9%). The mean IRCCP for Asian, Class-I, normodivergent cases was 27.2% (95% CI: 0.22-0.32; I2 = 0%). In Asian normodivergent cases, MRSL ranges from 3.28 to 4.43 mm with a 27.2% IRCCP for Class-I. Cone-beam computed tomography imaging is recommended for measuring the MRSL in the apex region particularly before molar distalization. Factors influencing MRSL and IRCCP include different races, skeletal patterns, facial types, and third-molar status.

Melatonin protects TEGDMA-induced preodontoblast mitochondrial apoptosis via the JNK/MAPK signaling pathway.

Resin monomer-induced dental pulp injury presents a pathology related to mitochondrial dysfunction. Melatonin has been regarded as a strong mitochondrial protective bioactive compound from the pineal gland. However, it remains unknown whether melatonin can prevent dental pulp from resin monomer-induced injury. The aim of this study is to investigate the effects of melatonin on apoptosis of mouse preodontoblast cells (mDPC6T) induced by triethylene glycol dimethacrylate (TEGDMA), a major component in dental resin, and to determine whether the JNK/MAPK signaling pathway mediates the protective effect of melatonin. A well-established TEGDMA-induced mDPC6T apoptosis model is adopted to investigate the preventive function of melatonin by detecting cell viability, apoptosis rate, expressions of apoptosis-related proteins, mitochondrial ROS (mtROS) production, mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) level. Inhibitors of MAPKs are used to explore which pathway is involved in TEGDMA-induced apoptosis. Finally, the role of the JNK/MAPK pathway is verified using JNK agonists and antagonists. Our results show that melatonin attenuates TEGDMA-induced mDPC6T apoptosis by reducing mtROS production and rescuing MMP and ATP levels. Furthermore, mitochondrial dysfunction and apoptosis are alleviated only by the JNK/MAPK inhibitor SP600125 but not by other MAPK inhibitors. Additionally, melatonin downregulates the expression of phosphorylated JNK and counteractes the activating effects of anisomycin on the JNK/MAPK pathway, mimicking the effects of SP600125. Our findings demonstrate that melatonin protects mDPC6T cells against TEGDMA-induced apoptosis partly through JNK/MAPK and the maintenance of mitochondrial function, offering a novel therapeutic strategy for the prevention of resin monomer-induced dental pulp injury.

Direct contact with endothelial cells drives dental pulp stem cells toward smooth muscle cells differentiation via TGF-ß1 secretion.

AIM: Prevascularization is vital to accelerate functional blood circulation establishment in transplanted engineered tissue constructs. Mesenchymal stem cells (MSCs) or mural cells could promote the survival of implanted endothelial cells (ECs) and enhance the stabilization of newly formed blood vessels. However, the dynamic cell-cell interactions between MSCs, mural cells and ECs in the angiogenic processes remain unclear. This study aimed to explore the interactions of human umbilical vein ECs (HUVECs) and dental pulp stem cells (DPSCs) in an in vitro cell coculture model. METHODOLOGY: Human umbilical vascular ECs and DPSCs were directly cocultured or indirectly cocultured with transwell inserts in endothelial basal media-2 (EBM-2) supplemented with 5% FBS for 6 days. Expression of SMC-specific markers in DPSCs monoculture and HUVEC+DPSC cocultures was assessed by western blot and immunofluorescence. Activin A and transforming growth factor-beta 1 (TGF-ß1) in conditioned media (CM) of HUVECs monoculture (E-CM), DPSCs monoculture (D-CM) and HUVEC+DPSC cocultures (E+D-CM) were analysed by enzyme-linked immunosorbent assay. TGF-ß RI kinase inhibitor VI, SB431542, was used to block TGF-ß1/ALK5 signalling in DPSCs. RESULTS: The expression of SMC-specific markers, α-SMA, SM22α and Calponin, were markedly increased in HUVEC+DPSC direct cocultures compared to that in DPSCs monoculture, while no differences were demonstrated between HUVEC+DPSC indirect cocultures and DPSCs monoculture. E+D-CM significantly upregulated the expression of SMC-specific markers in DPSCs compared to E-CM and D-CM. Activin A and TGF-ß1 were considerably higher in E+D-CM than that in D-CM, with upregulated Smad2 phosphorylation in HUVEC+DPSC cocultures. Treatment with activin A did not change the expression of SMC-specific markers in DPSCs, while treatment with TGF-ß1 significantly enhanced these markers' expression in DPSCs. In addition, blocking TGF-ß1/ALK5 signalling inhibited the expression of α-SMA, SM22α and Calponin in DPSCs. CONCLUSIONS: TGF-ß1 was responsible for DPSC differentiation into SMCs in HUVEC+DPSC cocultures, and TGF-ß1/ALK5 signalling pathway played a vital role in this process.

Effects of probiotics on the oral health of patients undergoing orthodontic treatment: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The effect of probiotics on oral health maintenance in orthodontic patients remains controversial. The aim of the study is to systematically review and assess the effects of probiotics on the oral health and microbiome of patients undergoing orthodontic treatment. SEARCH METHODS AND SELECTION CRITERIA: Databases including PubMed, Web of Science, Cochrane Library, ClinicalTrials.gov, and ProQuest Dissertations & Theses Global databases were searched from their inception until June 2022. Randomised controlled trials that assessed the effects of probiotics on clinical and microbial outcomes in patients undergoing orthodontic treatment were included. DATA COLLECTION AND ANALYSIS: Data screening and collection were performed, and the risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. The meta-analysis evaluated the effects of probiotics on Streptococcus mutans (S. mutans) and Lactobacillus counts. The quality of the evidence from the meta-analyses was assessed with Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: A total of 405 records were identified, of which 15 studies were included in the qualitative synthesis and 4 in the meta-analysis. The patients in all the included studies were treated with fixed orthodontic appliances. Results regarding clinical outcomes were controversial; four out of five studies reported no significant changes in plaque in the probiotic group (P > .05), and two out of three studies reported no significant changes in the gingival index (P > .05). Regarding microbial outcomes, the meta-analysis results revealed that probiotics significantly increased the likelihood of reducing the abundance of S. mutans to below 105 CFU/ml (risk ratio: 2.05 [1.54, 2.72], P < .001) and reduced the likelihood of increasing the abundance of S. mutans to beyond 106 CFU/ml (risk ratio: 0.48 [0.28, 0.83], P = .009). However, the quality of evidence according to the GRADE was moderate. CONCLUSIONS AND IMPLICATIONS: There is insufficient evidence to determine the clinical benefits of probiotics as a supplement for the oral health of patients undergoing orthodontic treatment. However, probiotics may have benefits in reducing the salivary S. mutans counts in orthodontic patients. REGISTRATION: PROSPERO (CRD42022366650).

[Safety evaluation of Tibetan medicine Qishiwei Zhenzhu Pills based on serum pharmacochemistry and network pharmacology].

To explore the mechanism of the active ingredients of Qishiwei Zhenzhu Pills in inhibiting the hepatorenal toxicity of the zogta component based on serum pharmacochemistry and network pharmacology, thereby providing references for the clinical safety application of Qishiwei Zhenzhu Pills. The small molecular compounds in the serum containing Qishiwei Zhenzhu Pills of mice were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Then, by comprehensively using Traditional Chinese Medicines Systems Pharmacology(TCMSP), High-throughput Experiment-and Reference-guided Database(HERB), PubChem, GeneCards, SuperPred, and other databases, the active compounds in the serum containing Qishiwei Zhenzhu Pills were retrieved and their action targets were predicted. The predicted targets were compared with the targets of liver and kidney injury related to mercury toxicity retrieved from the database, and the action targets of Qishiwei Zhenzhu Pills to inhibit the potential mercury toxicity of zogta were screened out. Cytoscape was used to construct the active ingredient in Qishiwei Zhenzhu Pills-containing serum-action target network, and STRING database was used to construct the protein-protein interaction(PPI) network of intersection targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out on the target genes by the DAVID database. The active ingredient-target-pathway network was constructed, and the key ingredients and targets were screened out for molecular docking verification. The results showed that 44 active compounds were identified from the serum containing Qishiwei Zhenzhu Pills, including 13 possible prototype drug ingredients, and 70 potential targets for mercury toxicity in liver and kidney were identified. Through PPI network topology analysis, 12 key target genes(HSP90AA1, MAPK3, STAT3, EGFR, MAPK1, APP, MMP9, NOS3, PRKCA, TLR4, PTGS2, and PARP1) and 6 subnetworks were obtained. Through GO and KEGG analysis of 4 subnetworks containing key target genes, the interaction network diagram of active ingredient-action target-key pathway was constructed and verified by molecular docking. It was found that taurodeoxycholic acid, N-acetyl-L-leucine, D-pantothenic acid hemicalcium, and other active ingredients may regulate biological functions and pathways related to metabolism, immunity, inflammation, and oxidative stress by acting on major targets such as MAPK1, STAT3, and TLR4, so as to inhibit the potential mercury toxicity of zogta in Qishiwei Zhenzhu Pills. In conclusion, the active ingredients of Qishiwei Zhenzhu Pills may have a certain detoxification effect, thus inhibiting the potential mercury toxicity of zogta and playing a role of reducing toxicity and enhancing effect.

PKCι Is a Promising Prognosis Biomarker and Therapeutic Target for Pancreatic Cancer.

BACKGROUND: As the highest prevalent pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) ranks the 7th lethal malignancy worldwide. The late diagnosis, chemotherapeutic resistance, and high associated mortality make PDAC a dilemma facing the oncologists. Protein kinase C (PKC) enzymes have been shown to be important in different cancer progression. METHODS: To understand the pattern of PKC enzymes in PDAC, we examined all PKC family member genes expression in PDAC and matched normal tissues. The critical role of PKCι was further investigated in different PDAC cells using cellular and molecular technology. RESULTS: We found that PRKCI (PKCι) was the most significantly overexpressed PKCs in pancreatic cancer. However, little is known about its role and regulation of oncogenic signaling pathways in pancreatic cancer. In this study, we confirmed the overexpression of PKCι in PDAC, and this high expression was associated with poor prognosis of patients. We proved that knockdown of PKCι by small interfering RNA or shRNA significantly inhibited pancreatic cancer cell growth and migration or invasion. Conversely, PKCι overexpression promoted pancreatic cancer cell growth and migration. Moreover, bioinformatical and technical studies informed the participation of PKCι in regression of apoptosis in PDAC cells, which may be related to the regulation of both PI3K/AKT and Wnt/ß-catenin pathways. CONCLUSIONS: Therefore, our results are adding more insight into the importance of PKCι in pancreatic cancer. PKCι induces pancreatic cancer progression through activation of PI3K/AKT and Wnt/ß-catenin signaling pathways, which may provide a promising therapeutic target for pancreatic cancer.

KCNN4-mediated Ca2+/MET/AKT axis is promising for targeted therapy of pancreatic ductal adenocarcinoma.

As a member of the potassium calcium-activated channel subfamily, increasing evidence suggests that KCNN4 was associated with malignancies. However, the roles and regulatory mechanisms of KCNN4 in PDAC have been little explored. In this work, we demonstrated that the level of KCNN4 in PDAC was abnormally elevated, and the overexpression of KCNN4 was induced by transcription factor AP-1. KCNN4 was closely correlated with unfavorable clinicopathologic characteristics and poor survival. Functionally, we found that overexpression of KCNN4 promoted PDAC cell proliferation, migration and invasion. Conversely, the knockdown of KCNN4 attenuated the growth and motility of PDAC cells. In addition to these, knockdown of KCNN4 promoted PDAC cell apoptosis and led to cell cycle arrest in the S phase. In mechanistic investigations, RNA-sequence revealed that the MET-mediated AKT axis was essential for KCNN4, encouraging PDAC cell proliferation and migration. Collectively, these findings reveal a function of KCNN4 in PDAC and suggest it's an attractive therapeutic target and tumor marker. Our studies underscore a better understanding of the biological mechanism of KCNN4 in PDAC and suggest novel strategies for cancer therapy.

Lipopolysaccharides affect compressed periodontal ligament cells via Eph-ephrin signaling.

OBJECTIVES: The aim of this study is to investigate the underlying mechanism of the recovery of periodontal ligament cells (PDLCs) sequentially exposed to inflammation and mechanical loading. MATERIALS AND METHODS: We divided PDLCs into four groups: control; compressive force (CF) alone (2.0 g/cm2 ); lipopolysaccharides (LPS) pretreatment (0.1 µg/ml) followed by simultaneous LPS and CF stimulation, simulating uncontrolled periodontitis; and LPS pretreatment followed by CF exposure, simulating controlled periodontitis. The expression of EphB4-ephrinB2 and EphA2-ephrinA2, and the level of osteoclastogenesis and osteogenesis were evaluated. RESULTS: Simultaneous stimulation by LPS and CF, compared with CF alone and sequential LPS and CF exposure, significantly suppressed EphB4 and enhanced ephrinA2 expression. Similarly, the most intense osteoclastic differentiation was observed under simultaneous LPS and CF stimulation, while sequential exposure to LPS and CF only slightly increased osteoclastic cell numbers. Both the activation of EphB4 signaling and ephrinA2 silencing lowered osteoclastic differentiation, which had previously been upregulated by simultaneous LPS and CF stimulation. These treatments also increased osteogenic differentiation. CONCLUSIONS: Simultaneous LPS and CF stimulation critically enhances osteoclastogenesis in PDLCs through the suppression of EphB4 and the induction of ephrinA2 signaling. Sequential LPS and CF exposure partially abolishes the osteolytic effects of simultaneous stimulation.

Antimicrobial Photodynamic Effect of Cross-Kingdom Microorganisms with Toluidine Blue O and Potassium Iodide.

Streptococcus mutans (S. mutans) and Candida albicans (C. albicans) are prominent microbes associated with rapid and aggressive caries. In the present study, we investigated the antimicrobial efficacy, cytotoxicity, and mechanism of toluidine blue O (TBO)-mediated antimicrobial photodynamic therapy (aPDT) and potassium iodide (KI). The dependence of KI concentration, TBO concentration and light dose on the antimicrobial effect of aPDT plus KI was determined. The cytotoxicity of TBO-mediated aPDT plus KI was analyzed by cell counting kit-8 (CCK-8) assay. A singlet oxygen (1O2) probe test, time-resolved 1O2 detection, and a 1O2 quencher experiment were performed to evaluate the role of 1O2 during aPDT plus KI. The generation of iodine and hydrogen peroxide (H2O2) were analyzed by an iodine starch test and Amplex red assay. The anti-biofilm effect of TBO-mediated aPDT plus KI was also evaluated by counting forming unit (CFU) assay. KI could potentiate TBO-mediated aPDT against S. mutans and C. albicans in planktonic and biofilm states, which was safe for human dental pulp cells. 1O2 measurement showed that KI could quench 1O2 signals, implicating that 1O2 may act as a principal mediator to oxidize excess iodide ions to form iodine and H2O2. KI could highly potentiate TBO-mediated aPDT in eradicating S. mutans and C. albicans due to the synergistic effect of molecular iodine and H2O2.

The interferon stimulated gene 20 protein (ISG20) is an innate defense antiviral factor that discriminates self versus non-self translation.

ISG20 is a broad spectrum antiviral protein thought to directly degrade viral RNA. However, this mechanism of inhibition remains controversial. Using the Vesicular Stomatitis Virus (VSV) as a model RNA virus, we show here that ISG20 interferes with viral replication by decreasing protein synthesis in the absence of RNA degradation. Importantly, we demonstrate that ISG20 exerts a translational control over a large panel of non-self RNA substrates including those originating from transfected DNA, while sparing endogenous transcripts. This activity correlates with the protein's ability to localize in cytoplasmic processing bodies. Finally, these functions are conserved in the ISG20 murine ortholog, whose genetic ablation results in mice with increased susceptibility to viral infection. Overall, our results posit ISG20 as an important defense factor able to discriminate the self/non-self origins of the RNA through translation modulation.

S100A16 promotes metastasis and progression of pancreatic cancer through FGF19-mediated AKT and ERK1/2 pathways.

The S100 protein family genes play a crucial role in multiple stages of tumorigenesis and progression. Most of S100 genes are located at chromosome locus 1q21, which is a region frequently rearranged in cancers. Here, we examined the expression of the S100 family genes in paired pancreatic ductal adenocarcinoma (PDAC) samples and further validated the expression of S100A16 by immunohistochemistry staining. We found that S100A16 is significantly upregulated in clinical PDAC samples. However, its roles in PDAC are still unclear. We next demonstrated that S100A16 promotes PDAC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Knockdown of S100A16 induces PDAC cell cycle arrest in the G2/M phase and apoptosis. Furthermore, we also demonstrated that S100A16 promotes PDAC cell proliferation, migration, and invasion via AKT and ERK1/2 signaling in a fibroblast growth factor 19 (FGF19)-dependent manner. Taken together, our results reveal that S100A16 is overexpressed in PDAC and promotes PDAC progression through FGF19-mediated AKT and ERK1/2 signaling, suggesting that S100A16 may be a promising therapeutic target for PDAC. S100A16 was upregulated in PDAC and associated with prognosis of PDAC patients. S100A16 regulates apoptosis and the cell cycle of pancreatic cancer cells. S100A16 promotes the progression of pancreatic cancer by AKT-ERK1/2 signaling. S100A16 may be a promising therapeutic target for PDAC.

Effect of Optimized Irrigation With Photon-Induced Photoacoustic Streaming on Smear Layer Removal, Dentin Microhardness, Attachment Morphology, and Survival of the Stem Cells of Apical Papilla.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the effect of optimized irrigation with photon-induced photoacoustic streaming (PIPS) activation of different irrigants (distilled water or ethylenediaminetetraacetic acid [EDTA]) on smear layer removal, dentin microhardness, attachment morphology, and survival of stem cells of the apical papilla (SCAP) in an organotypic root canal model. STUDY DESIGN/MATERIALS AND METHODS: A total of 144 standardized root segments were randomly allocated into 6 groups for irrigation: (i) NaOCl group, (ii) NaOCl + EDTA group, (iii) NaOCl + PIPS (distilled water) group, (iv) NaOCl + PIPS (EDTA) group, (v) NaOCl + EDTA + PIPS (distilled water) group, and (vi) NaOCl + EDTA + PIPS (EDTA) group. Each group was divided into four subgroups for assessment: (i) dentin cleanliness; (ii) dentin microhardness; (iii) cell attachment morphology; and (iv) viable SCAP quantification. RESULTS: Compared with the control groups, the NaOCl + EDTA + PIPS (EDTA) group showed higher efficiency in smear layer removal and in increasing SCAP viability with more stretched cellular morphology. There were no statistically significant differences in either smear layer removal effect, dentin microhardness, attachment morphology, or survival of SCAP among the other groups when optimized with PIPS (distilled water or EDTA) (P > 0.05). CONCLUSIONS: Our findings indicated that irrigation optimized with PIPS activation of EDTA for 40 seconds was conducive to smear layer removal without additional dentin microhardness decrease. Additionally, this irrigation created more cell-friendly dentin conditioning than other approaches, which was beneficial for the attachment and survival of SCAP. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Cemental tear: Literature review, proposed classification and recommendations for treatment.

Cemental tears are an important condition of relevance to Endodontics but are often overlooked. A cemental tear is the partial or complete detachment of the cementum from the cemento-dentinal junction or along the incremental line within the body of cementum. The limited attention received is most likely due to the limited awareness amongst dental professionals and challenges in accurately diagnosing them, resulting in misdiagnosis and erroneous treatment. The aim of this review is to describe the: (i) epidemiology and predisposing factors; (ii) clinical, radiographic and histological features and (iii) the clinical management and treatment outcomes of cemental tear. The review included 37 articles published in English that comprised eight observational studies and 29 case reports. The prevalence of cemental tears was reported to be lower than 2%; whilst the incidence remains unknown. Internal factors due to the inherent structural weakness of cementum and its interface with the dentine, and external factors that are associated with stress have been proposed as the two mechanisms responsible for the development and propagation of cemental tears. Predisposing factors that have been implicated were tooth type, gender, age, previous root canal treatment, history of dental trauma, occlusal trauma and excessive occlusal force; however, evidence is limited. Common clinical and radiographic manifestations of cemental tears resemble the presentations of primary endodontic diseases, primary periodontal diseases and combined endodontic-periodontal lesions. Clinical management tended to focus on complete removal of the torn fragments and periodontal treatment, often combined with regenerative treatment. In this article, a new classification for cemental tears is developed that consists of classes 0 to 6 and stages A, B, C and D based on the: (i) location and accessibility of the torn cemental fragment; (ii) the pattern and extension of the associated bony defect in relation to the root length and (iii) the number of root surface/s affected by the cemental tear/s and the associated bony defect. Recommendations for treatment strategies are also provided and linked to the classification to aid in streamlining the process of treatment decision making.

Do different cone beam computed tomography exposure protocols influence subjective image quality prior to and after root canal treatment?

OBJECTIVES: The current study aimed to evaluate different CBCT exposure protocols and influencing factors affecting the subjective image quality of scans taken for endodontic indications. MATERIALS AND METHODS: Twelve extracted teeth, comprising of two sets of maxillary molars, premolars, canines and incisors, mandibular premolars, and molars, were endodontically treated, and either received a fiber or metal post. The teeth were scanned by CBCT imaging before and after root canal treatment, and after post insertion. Each scan was performed thrice, using an ultra low dose (ULD), standard (SM), and high-resolution mode (HR), respectively. Twelve observers-4 endodontists, 4 periodontists, and 4 radiologists-assessed the subjective image quality using visual analogue scales (VAS). Potential influencing factors were evaluated including acquisition mode, observer specialty, stage of treatment, type of post, and type of tooth, using one-way ANOVA and T test. RESULTS: Teeth scanned with the ULD had the highest average VAS score (72.5), followed by HR (70.2), and SM (69.0) for values pooled from all teeth and observers. CBCT acquisition mode was not a significant influencing factor on the VAS scores. Observer specialty, stage of treatment, type of post, and type of tooth were significant influencing factors. CONCLUSIONS: Based on the present in vitro data, a low-dose CBCT mode seems not to negatively affect the perception of image quality. CLINICAL RELEVANCE: The findings from this in vitro study demonstrate that a low-dose CBCT mode might have potential for diagnostics prior to or following endodontic treatment.

Three-dimensional morphologic classifications and analysis of canal isthmuses in permanent molars.

PURPOSE: To investigate the three-dimensional morphology of isthmuses in molars according to their boundary characteristics using micro-computed tomography (micro-CT). METHODS: Micro-CT reconstructed images of 248 molars were evaluated. Isthmuses were classified into four types based on the boundary characteristics: isthmus with roof, isthmus with floor, band-shaped isthmus, and isthmus without boundary. The tooth and root with isthmuses, the number and location of the isthmuses in the root, and the canal configurations were recorded. The maximum of the major diameter of all canal cross-sections in one isthmus (dmax), the minor diameter of the canal in same cross-section (dmin), the distance between the dmax cross-section and apex (Dm-a), isthmus length (Li), and distance from the isthmus ending cross-section to apex (De-a) were measured and analysed with a significance threshold set to 5%. RESULTS: Isthmuses were present in 75.4% specimens. The four types of isthmuses were found in various molars and roots. Their distribution in different root locations and canal configurations was significantly different. The dmax, dmin, Li, and De-a were analysed according to different molars and different isthmus types; their respective median values were 2.508 mm, 0.07 mm, 3.09 mm, and 3.96 mm. CONCLUSION: The three-dimensional classification of isthmuses according to the boundary characteristics provides a comprehensive picture of the isthmus in molars. Their corresponding distributions in different molars, location in roots, and canal configurations will be helpful in predicting the type of isthmus based on the tooth position and canal configurations.

IL-17 alters the mesenchymal stem cell niche towards osteogenesis in cooperation with osteocytes.

Bone remodeling is a strictly regulated dynamic process that cycles between bone formation and resorption, and interleukin-17 (IL-17) critically orchestrates the activation and differentiation of both osteoblasts and osteoclasts. Mesenchymal stem cells (MSCs) within their native environment receive biochemical stimuli from surrounding cells that influences their differentiation into bone precursors, while the roles of osteocytes in regulating the osteogenic differentiation of MSCs remain unclear. This study investigated the specific roles of IL-17 signaling cascades and osteocyte-specific pathways in the osteogenesis of MSCs. Using a transwell coculture (CC) system, we explored the effects of osteocytes and osteoblasts on the osteogenesis of MSCs with and without IL-17 supplementation. A polycaprolactone (PCL) three-dimensional (3D) culture model was used to evaluate their osteogenic potential in the presence of osteocytes and IL-17. Notably, IL-17 induced osteogenesis in MSCs, which could be attenuated by blocking IL-17 receptor A. The osteogenic differentiation of MSCs promoted by IL-17 was further enhanced by CC with osteocytes. Moreover, proinflammatory cytokines IL-6 and IL-1ß played an important role in IL-17-dependent differentiation, via the phosphorylation of AKT, signal transducer and activator of transcription 3, and extracellular signal-regulated kinase 1/2 signaling pathways in the MSC niche. The present study confirms a synergistic effect of osteocytes and IL-17 in the production of biochemical signals to stimulate the osteogenic differentiation of MSCs, which could be further promoted in the PCL 3D-scaffold. These findings provide important insight into the mechanisms of MSCs activation and osteogenic differentiation within the native stem cell niche, and suggest a possible role of IL-17 in bone tissue engineering.

Low-level laser-aided orthodontic treatment of periodontally compromised patients: a randomised controlled trial.

Low-level laser irradiation (LLLI) shows effects in orthodontic pain relief and periodontal inflammation control. The aim of this article is to investigate the analgesic and inflammation-modulatory effects of low-level laser irradiation among orthodontic patients with compromised periodontium. A randomised controlled trial with split-mouth design was conducted in 27 adults with treated and controlled chronic periodontitis over 6 months. One side of the dental arch underwent repeated treatment under a 940-nm diode laser (EZlase; Biolase Technology Inc.) with a beam size of 2.8 cm2 for 60 seconds at 8.6 J/cm2, whilst the other side received pseudo-laser treatment. Laser irradiation was applied repeatedly for 8 times during the first 6 weeks after bracket bonding and monthly thereafter until the end of orthodontic treatment. Subjective pain (assessed by visual analogue scale in pain diary and by chairside archwire activation), periodontal status (assessed by periodontal clinical parameters), cytokines in gingival crevicular fluid (interleukin 1ß, prostaglandin E2, substance P) and periodontopathic bacteria (Porphyromonas gingivalis and Treponema denticola) in supragingival plaque were assessed. The intensity of pain was lower on the laser-irradiated side at multiple follow-up visits (P < 0.05). The pain subsided 1 day earlier on the laser side, with a lower peak value during the first week after initial archwire placement (P < 0.05). The laser side exhibited a smaller reduction in bite force during the first month (mean difference = 3.17, 95% CI: 2.36-3.98, P < 0.05 at 1-week interval; mean difference = 3.09, 95% CI: 1.87-4.32, P < 0.05 at 1-month interval). A smaller increase was observed in the plaque index scores on the laser side at 1-month (mean difference = 0.19, 95% CI: 0.13-0.24, P < 0.05) and in the gingival index scores at the 3-month follow-up visit (mean difference = 0.18, 95% CI: 0.14-0.21, P < 0.05). Laser irradiation inhibited the elevation of interleukin-1ß, prostaglandin E2 and substance P levels during the first month (P < 0.05). However, no intergroup difference was detected in the bacteria levels. Low-level laser irradiation exhibits benefits in pain relief and inflammation control during the early stage of adjunctive orthodontic treatment in periodontally compromised individuals.