This study aimed to evaluate the effect of the maxillary first molar intrusion mechanics with mini-implant anchorages on the Von Mises stress and initial displacement using finite element analysis. A three-dimensional finite model was established using Mimics 17.0, Geomagic Studio 2014, Unigraphics NX 8.5 and Ansys workbench 15 software based on original cone beam computed tomography data. Four loading methods were used. The displacement of the maxillary first molar was calculated along the x-, y- and z-axes, and the von Mises stress distribution was visualized using color-coded scales. Most of the stress was concentrated on the cervical or middle third of the roots of the maxillary first molar and decreased toward the apex in all models. The minimum and more uniform stress distribution appeared around the apical third of the roots. The strongest stress on the periodontal ligament (PDL) and alveolar bone was always around the cervical and root furcation. After intrusion, the maxillary first molar was bodily intruded without tipping in model 1, whereas buccal tipping was observed in models 2 and 4. In model 3, the molar had the tendency of mesial-lingual rotation. The vertical displacements were 95.3%, 79.6%, 95.3% and 79.6% of the total displacements of models 1-4, respectively. All cusps were uniformly intruded in models 1 and 3. Buccal cusps were intruded 50% more than the lingual cusps in model 2. All of the cusps were intruded except for the distal-lingual cusp in model 4. The apical third of the roots suffered the minimum stress and was not prone to evident resorption during intrusion, whereas the maximum stress on PDL was also maintained within the normal physiological range. Four loading methods were available for intrusion. Model 1 was the best, followed by models 2, 3 and 4. The tooth cusp conditions should be considered during molar intrusion.

Diffuse large B-cell lymphoma (DLBCL) seriously threatens public health, and drug resistance is a formidable obstacle to DLBCL therapy. MicroRNAs (miRNAs) have been certified to act as a momentous regulator in drug resistance of DLBCL. This study aimed to ascertain the latent function and mechanism of miR-101-3p in modulating the resistance of DLBCL cells to ibrutinib. The differentially expressed miRNAs were identified by bioinformatics analysis of GSE117063 and GSE173080 datasets. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure the expression levels of miR-101-3p and ATP-binding cassette subfamily C member 5 (ABCC5). The resistance of DLBCL cells to ibrutinib was determined by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and Western blot assays. The relationship between miR-101-3p expression level and ABCC5 expression level was analyzed using dual-luciferase reporter assay and Pearson correlation test. MiR-101-3p was significantly downregulated in DLBCL cells according to the results of the bioinformatics analysis. A low miR-101-3p expression level predicted resistance of DLBCL cells to ibrutinib. Upregulation of miR-101-3p sensitized the constructed ibrutinib-resistant DLBCL (DLBCL/ibR). Our findings revealed that ABCC5 was targeted by miR-101-3p, and ABCC5 was abundantly expressed in DLBCL/ibR tissue samples and cells. Furthermore, miR-101-3p mimics overturned the influences of ABCC5 upregulation on the resistance of DLBCL cells to ibrutinib. MiR-101-3p played a suppressive function in the resistance of DLBCL cells to ibrutinib via inhibiting ABCC5 expression, which might represent a potent therapeutic target for DLBCL.

Preeclampsia (PE) causes fetal growth restriction. Although trophoblastic epithelial-mesenchymal transition (EMT) dysfunction has been reported to be associated with PE, the underlying pathological mechanisms have not been fully elucidated. BRCA1-associated protein 1 (BAP1) is suggested to play a crucial role in regulating trophoblast biological activities, yet, the exact molecular mechanisms by which BAP1 regulates EMT have not been investigated. Thus, this study explored the role of BAP1 overexpression in EMT and its underlying mechanism. Invasion of JEG-3 and HTR-8/SVneo cells was used to assess the role of BAP1 in PE. BAP1 expressing vectors, and short-hairpin RNA targeting BAP1 were constructed, and multiple analytical assays were performed, such as CCK-8, Western blotting, qPCR, trans-well assay, invasion, and migration assay, to depict the underlying mechanism of BAP1 in EMT. Our results showed that silencing BAP1 in human normal trophoblast HTR8/SVneo cells promoted their proliferation, invasion, and migration, and the expressions of E-cadherin, Bax, cleaved caspase 3, and PTEN were downregulated while N-cadherin, vimentin, Bcl-2, p-PI3K, p-Akt, and p-mTOR were upregulated. On the other hand, overexpressing BAP1 in human choriocarcinoma JEG-3 cells suppressed their proliferation, invasion, and migration, and the protein expressions of E-cadherin, Bax, and cleaved caspase 3 and PTEN were upregulated, while the expressions of N-cadherin, Bcl-2, vimentin, p-PI3K, p-Akt, and p-mTOR were downregulated. Mechanistically, it was found that BAP1 overexpression suppressed the PI3K/Akt/mTOR signaling pathway via deubiquitinating phosphatase and tensin homolog (PTEN). Our findings indicate a potential therapeutic target of PE.

To evaluate the occurrence and morphological characteristics of related anatomical structures in the anterior mental foramen region and to verify the measurement consistency by cone beam CT (CBCT) and specimen measurement. Thirty-two mandibular specimens were selected to measure the relevant anatomical structures and to take CBCT images of the specimens for 3D reconstruction using NNT-Viewer. The studies included the occurrence and diameter of the mental foramen, accessory foramen, median lingual foramen, the distance from the lower margin of the foramen to the lower margin of the mandible, and the distance from the upper margin of the foramen to the crest of the alveolar ridge. Thirty-two specimens including a total of 59 central lingual foramens, with a 100% probability of occurrence. Four specimens were found to have an accessory mental foramen, of which 1 had bilateral accessory mental foramens. Compared with direct observation, there were differences in the number of central lingual foramens in 3 specimens. The mean distance between the upper mental foramen edge and the alveolus crest was 13.7 mm. There were statistically significant differences between the two methods in measuring the distance (mm) between the central lingual aperture and the alveolar crest (P<0.05). Except for the distance between the central lingual aperture and the alveolar crest (ICC=0.658), the ICC of the other study variables was above 0.85. The measurement results of the two methods showed a high degree of consistency. The measurement results of CBCT in this study showed a high degree of consistency with the measurement results from specimens, and the relevant anatomical structures of jaw bones could be analyzed using CBCT before the operation in the intermental foramen region.

In this study, ultra-high-resolution micro-computed tomography (micro-CT) was used to classify the root canal morphology of the distobuccal root of the maxillary first molar and investigate the incidence of accessory root canals, as well as to identify some aspects of their association with root canal re-infection during and after molar-infected root canal treatment. The specimens used were 100 maxillary first molars from Japanese individuals held in the collection of the Department of Anatomy of Tokyo Dental College. They were scanned by micro-CT, after which three-dimensional reconstruction was conducted, the pulp cavity and accessory root canals were observed, the root canal morphology was classified, and the incidences of the different types of accessory root canals were calculated. The distobuccal root of the maxillary first molar was a single root in all teeth from Japanese individuals. The main root canal was classified as Type I in 98.0% of cases, the incidence of lateral branches was 27.0%, and their incidence on the apical side was higher than that previously reported. These results suggest that, despite the simplicity of the root canal, the existence of accessory root canals should be borne in mind during root canal treatment.

The aim of regenerative medicine is to restore the original functions of tissues and organs damaged by disease or impairment. Stem cell transfusion has been used clinically as regenerative therapy in a wide range of fields. This therapy promotes regeneration of partially damaged tissues or organs by transfer of tissue stem cells. Teeth are produced from dental germ, which is induced by interactions between epithelial and mesenchymal stem cells. Wnt signals are heavily involved in this process. Furthermore, it has been shown that β-catenin is expressed in the nucleus of odontoblasts and dentinal cells located immediately under repaired dentine after pulpotomy, and that macrophages in dental pulp express Wnt10a, suggesting involvement of Wnt10a in odontoblasts in generation and repair processes. However, little is known about the involvement of Wnt10a in odontoblasts in regenerated pulp tissues. Hayashi et al. transplanted dental pulp, bone marrow, adipose stem cells, or culture supernatants derived from each of them in the ectopic tooth transplantation. As a result, we have succeeded in regenerating dental pulp tissue that expresses the dental pulp marker TRH-DE, regardless of the transplantation. In this study, we used this model to examine morphologically how Wnt10a and odontoblasts change with time in regenerated dental pulp. We then analyzed the dynamics of Wnt10a in dentinal induction in dental pulp stem cells. The results of this study showed an increase in odontoblasts with increased regeneration of dental pulp, and these odontoblasts expressed Wnt10a. Expression of DSPP increases upon inhibition of expression of DKK1, and induction of dentinal differentiation occurs via expression of Wnt10a in dental pulp regeneration. Therefore, Wnt10a is a candidate as a non-cellular agent for induction of dental pulp regeneration with dentine-inducing capacity.

Previous studies have reported the up-regulated expression of protein O-fucosyltransferase 1 (POFUT1) in several human malignant tumors. This study purposes to explore the relevance of POFUT1 expression to the clinical and biological characteristics of salivary gland adenoid cystic carcinoma (SACC). 54 clinical SACC samples were applied in immunohistochemistry to evaluate the practical expression of POFUT1. The cells from human submandibular gland (HSG), and the cell lines from salivary gland adenoid cystic carcinoma (SACC-83, SACC-LM) were applied in quantitative PCR and Western blots to confirm the elevated POFUT1 expression in SACC. The shRNA of POFUT1 were delivered into SACC lines to knock down POFUT1 expression, and then, the capacities of progressing, proliferating, colony forming and surviving in the SACC lines were evaluated. The clinical samples from SACC patients were found exhibiting a noticeably robuster POFUT1 expression compared to the noncancerous samples. Statistical analysis indicated a significant correlation of POFUT1 expression to the T classification of SACC. Similarly, the POFUT1 expression in SACC lines was also elevated compared to the normal salivary gland. The decreased POFUT1 expression in SACC lines remarkably suppressed cell proliferation, colony amount and survival. Therefore, the elevated POFUT1 expression enhances the proliferation and survival of SACC, which implicates that POFUT1 could be used as an index for SACC prognosis and a potential target for future therapy.

Salivary glands are exocrine glands that secrete saliva, which plays an important role in the maintenance of oral health. Few reports exist on the contralateral salivary gland that is not directly affected when one salivary gland is affected by sialolithiasis, radiation therapy, or a tumor. In the present study, we investigated the changes in the contralateral submandibular gland in mice following the excision of unilateral salivary gland. Outcomes of this study showed that the unilateral submandibular and sublingual glands resection resulted in a significant increase in the weight of the remaining submandibular gland after 21 days following the unilateral resection of salivary gland. The appearance rate of the proliferating cells by cell type constituting the submandibular gland parenchyma significantly increased in the acinar cells of the contralateral submandibular gland, 7 days after unilateral resection of the submandibular and sublingual glands. This suggests that the unilateral submandibular and sublingual glands resection resulted in proliferation of the acinar cells in the contralateral submandibular gland. The area of the acini comprising the submandibular gland significantly increased in the remaining submandibular gland after 21 days following unilateral salivary gland resection, suggesting that the acinar cells proliferated as early as 7 days after salivary gland resection, resulting in increased acinar area and submandibular gland weight at 21 days post resection. The increased weight of the remaining contralateral submandibular gland may be attributable to the resection, owing to the proliferation and increased area of the acinar cells to compensate for the loss of salivary gland function.

Recently, low level laser therapy (LLLT) has been reported to promote wound healing of fractures, tooth extraction sockets and bone-dental implants osseointegration. In this study, we investigated the effects of LLLT on cell proliferation, differentiation and calcification of rat bone marrow-derived osteoblast-like cells using blue LED light irradiation at a wavelength of 455 nm. The irradiation conditions were as follows; LED with a wavelength of 455 nm, 510 mW output power (measured value in the irradiated field: 100 mW/cm²), distance: 20.8 mm, and irradiation for 14 seconds every 1.5 hours at an energy of 5.6 joules/cm² (up to 4.5 hours). The experimental groups were divided into 4 groups; control group, LED light-irradiation group, FGF-containing media group and LED light-irradiation and FGF-containing media group (n=3). The cell proliferative ability was determined using Cell Counting Kit-8 immediately after the first LED irradiation, after 1.5, 3.0, 4.5 and 12 hours by ELISA. Lab assay ALP was used to search for cell differentiation potential, and ALP activity levels in the samples were determined after 3 and 7 days. And the ALP staining was also performed after 7 days, and the ALP staining positive was determined by analyzing the percentage of stained area in each well. For the search of cellular calcification activity, Alizarin Red staining was used to determine its positivity rate by analyzing the stained area fraction of each well after 14 and 28 days. In all the searched results, both the cell proliferation and differentiation abilities were highest in the LED group. And the calcification ability was significantly higher in the LED, FGF and LED▪FGF groups than that in the control group. The results of this study suggested that LLLT with blue LED light irradiation was useful for bone tissue regeneration.

The incidence of human papillomavirus (HPV)-positive oral squamous cell carcinoma (OSCC) is reportedly higher in Asia than in Central/South America, Europe, and Africa. To date, there were many studies on HPV-positive oropharyngeal SCC (OPSCC). However, little is known about the potential variations in the incidence, racial features, and clinical outcomes in patients with HPV-positive OSCC. Hence, the purpose of this study was to examine the prevalence of HPV subtypes in OSCC and to study the patient characteristics and outcomes in the Japanese population. This study was conducted between 2009 and 2013 at Aichi Cancer Center Hospital, Nagoya, Japan and included patients who were newly diagnosed and histopathologically confirmed cases of OSCC. The study included 67 patients who met the inclusion criteria. All patients underwent definitive surgery, with or without chemotherapy. HPV subtypes in the biopsy samples were identified by polymerase chain reaction (PCR). The clinical factors and survival outcomes in patients with HPV-positive and HPV-negative OSCC were compared. Cox regression analysis was performed to determine the prognostic factors associated with overall survival (OS). The prevalence of HPV-positive OSCC was 10.4% and was predominant in males. HPV 16, which was the most common subtype identified, was predominantly observed in males. The clinical factors and survival outcomes (OS) did not differ between patients with HPV-positive and HPV-negative OSCC. Since the prevalence of HPV-positive OSCC is very low compared to that of OPSCC, it was difficult to achieve adequate power for survival analysis. However, in the future, additional studies with large sample sizes should be conducted to study the effect of clinical features on the prognosis of patients with HPV-positive OSCC.

The development of the submandibular gland is mediated by epithelial-mesenchymal interactions; the acini and ducts are immature at birth and proliferate and differentiate after birth. Limited information is available on epigenetic modifications via histone modifications during the early phase of salivary gland development. Therefore, the present study examined changes in the expression and localization of Jmjd3 to clarify the role of the H3K27me3 epigenetic modification in the postnatal development of the submandibular gland in mice. Morphological, immunohistochemical, and molecular biological assays were performed using submandibular glands harvested from mice at birth on day 0 to 10 weeks of age. On day 0, submandibular glands were characterized by the presence of terminal tubules and ducts within abundant connective tissue. The proliferation and differentiation of ductal cells in submandibular glands peaked by day 7, and the structure of submandibular glands matured to mimic that of adult mice by day 28. Jmjd3-positive cells were mostly found in connective tissue on day 0. After day 7, most of these cells were detected in the ducts. As submandibular glands continued to develop, the number of Jmjd3-positve cells significantly decreased irrespective of the location. The mRNA expression level of Jmjd3 continued to increase until day 7 and gradually decreased after day 14. Collectively, the present results demonstrated the development and differentiation of mouse submandibular gland tissue concurrent with significant changes in the expression and localization of Jmjd3 during the early postnatal period. Therefore, epigenetic modifications via histone H3K27me3 demethylation occur as the submandibular gland develops.