Good facial expression is an important goal of orthognathic surgery because facial expression has a considerably greater influence on humans’ aesthetic judgements than facial profile alone. However, to date, no reports have attempted to predict post-operative smiles from straight faces. The aim of this study was to evaluate the effectiveness of different techniques to create a posed smile (virtual) from a straight face (original). Twenty-five volunteers with no medical history that would interfere with a straight face or a posed smile were enrolled. After creating homologous models from the straight face and posed smile models, we assessed the ability of the principal component (PC) method and the improved Manchester (i-M) method to create a posed smile (virtual) from a straight face (original). Positive errors for the PC and i-M were 1.4 ± 0.5 mm, 0.9 ± 0.4 mm, respectively, and there was a significant difference. Although there were significant differences in error, the error of two methods, including homologous modeling techniques and principal component analysis, were clinically small and useful for predicting change in facial expression.

Ingestion of excess systemic fluoride results in physiological and pathological disturbances of bone homeostasis. We and others have established that treatment with 50 μM sodium fluoride (NaF) is safe and effective for bone remodeling in cellular and animal models. This study aimed to study the effects of treatment with 50 μM NaF on macrophage-driven osteoclastogenesis and to characterize the function of 50 μM NaF in alveolar bone resorption during aging. Murine RAW264.7 monocytic cells were treated with RANKL in the presence or absence of 50 μM NaF. The mRNA expression levels of Cathepsin K and nuclear factor-activated T-cell cytoplasmic 1 (NFATc1), which are involved in the mechanism of osteoclast induction, were measured using quantitative real time RT-PCR. An experimental 50 μM NaF-treated aging mouse model was used to confirm alveolar bone resorption. Micro-CT was used to assess bone loss and immunohistochemistry was performed to detect the protein expression levels of RANKL and Cathepsin K in periodontal tissues. Treatment of RAW264.7 cells with 50 μM NaF repressed osteoclastogenesis. Micro-CT results confirmed that treatment with 50 μM NaF alleviated alveolar bone resorption in aging. Immunohistochemical analysis revealed decreased expression levels of RANKL and cathepsin K in 50 μM NaF-treated mice during aging. Taken together, these results contribute fascinating experimental clues that 50 μM NaF has the potential to function as an anti-resorptive agent during alveolar bone aging.

Family with sequence similarity 20, member A (Fam20a) encodes a pseudokinase which is regarded to facilitate the role of Fam20c in phosphorylating secreted proteins. Fam20c deficiency causes Raine Syndrome in human and impaired the amelogeneis, dentiogenesis and osteogenesis in mice. Mutations in Fam20a are associated with Amelogenesis Imperfecta and Enamel-Renal Syndrome in human. Similarly, abrogation of Fam20a in ectoderm caused Amelogeneis Imperefeca in mice, however, the global knock-out of Fam20a in mice showed few anomaly in dentin and bone. In this study, the Fam20a^LacZ mice showed that at the E17.5, the LacZ staining was located in the osteogenic lining of calvarium and mandibular bone, odontoblasts, ameloblasts, the gingival and subcutaneous fibroblasts. During the postnatal life, the LacZ staining was detected in the osteogenic and gingival cells in mandibular bone, as well as the osteogenic and the marrow cells in long bone, but excluded from the joint cartilage. Both the LacZ staining in the mandibular and long bone became faint with the life increased. To address if Fam20a is required for the role of Fam20c during the dentinogenesis and osteogenesis, we first examined the mandibular bone and femur of the Wnt1-cre;Fam20a^f/f, Osr2-cre;Fam20a^f/f and Col1-cre; Fam20a^f/f mice. The gross views and X-ray plain images showed no difference in the tissue morphology and mineralization density between these conditional knock-out mice and their controls. Our findings suggested that Fam20a was not required by Fam20c during dentinogenesis and osteogenesis.

To investigate the effects of circ_0001017 as a molecular sponge adsorbing miR-197-3p to regulate PNLIP signaling on the proliferation, apoptosis and glycolysis of pancreatic ductal adenocarcinoma (PDAC) cells, the expressions of circ_0001017, miR-197-3p and PNLIP in PDAC tissues and cells were detected. The dual-luciferase reporter assay and RNA-binding protein immunoprecipitation assay were used to verify the targeting relationship between miR-197-3p and circ_0001017 or PNLIP. The expressions of circ_0001017/miR-197-3p/PNLIP in cells were interfered and they were grouped. The proliferation activity and apoptosis of the cells were measured by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Glucose, lactate, and ATP detection kits were used to assess glucose consumption, lactate production, and ATP levels. Compared with paracancerous tissues, miR-197-3p expression in PDAC tissues was significantly up-regulated, while circ_0001017 and PNLIP expressions were decreased (all P<0.05). Compared with negative control group, cell proliferation and glycolysis were inhibited, and apoptosis was induced after circ_0001017 overexpression (P<0.05). Circ_0001017 knockdown promoted PDAC cell proliferation and aerobic glycolysis, and inhibited cell apoptosis, which was partially rescued by miR-197-3p inhibitor and PNLIP knockdown (all P<0.05). miR-197-3p overexpression could promote proliferation and glycolysis of PDAC cells and inhibit cell apoptosis, which could be partially rescued by PNLIP overexpression (P<0.05). Circ_0001017 regulated the miR-197-3P/PNLIP axis and played a protective role in PDAC progression. It could inhibit the proliferation of PDAC cells, induce the apoptosis of tumor cells, and reduce the aerobic glycolysis capacity of the cells.

MCT1 is an important regulator in glycolysis and has significant effects on inflammatory responses and osteoclast differentiation etc. This study was to study the effects and mechanism of MCT1 in chondrocytes injury and inflammatory responses. ATDC5 cells with stably transfection of MCT1shRNA were treated with 5 μg/mL of LPS. Cell viability was determined by MTT assay. The mRNA and protein expressions were detected by qRT-PCR and western blotting, respectively. The concentrations of cytokines in culture medium were measured by ELISA. ROS generation was tested by 2,7-dichlorofluorescein diacetate (DCFH-DA). The results showed that MCT1 was increased by LPS treatment in ATDC5 cells in a dose dependent manner. MCT1 knockdown improved the survival of LPS-treated ATDC5 cells. MCT1 knockdown also decreased LPS-induced expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNFα) and oxidative stress mediators (iNOS, COX-2 and NOX-4) in ATDC5 cell. Importantly, PFKFB3 overexpression reversed the anti-inflammatory and anti-oxidative stress effects of MCT1 knockdown in LPS-induced ATDC5 cells. These results indicated that MCT1 knockout decreased the expression of inflammatory mediators and oxidative stress mediators induced by LPS through regulating PFKFB3. The study provides a potential target for the prevention or treatment of osteoarthritis (OA) and rheumatoid arthritis (RA).

Multiple myeloma is a frequent hematological malignancy. Although progress has been made in therapeutic strategies, the prognosis of multiple myeloma is far from satisfactory. Therefore, it is imperative to investigate the precise mechanism of multiple myeloma progression. Lysine Demethylase 4C (KDM4C) was demonstrated to be a vital regulator in cancers, while its action on multiple myeloma remains elusive. Thus, we aimed to investigate the effect of KDM4C on multiple myeloma progression and explored the precise mechanism of action. In this study, 70 multiple myeloma patients and 45 normal donors (volunteers) were enrolled. Results showed that KDM4C was highly expressed in plasma of 70 multiple myeloma patients and multiple myeloma cells. Knockdown of KDM4C suppressed proliferation and migration of multiple myeloma cells. Besides, JAG1 expression was enhanced in plasma of 70 myeloma patients and multiple myeloma cells. JAG1 expression was positively correlated with KDM4C expression. Furthermore, KDM4C knockdown suppressed Notch signaling proteins Notch-1, NICD-1, and Hes-1 in multiple myeloma. Moreover, KDM4C knockdown suppressed the proliferation and migration of multiple myeloma cells through down-regulating JAG1 expression. Collectively, KDM4C promotes the proliferation and migration of multiple myeloma cells by up-regulating JAG1 gene expression. KDM4C may be a promising target for multiple myeloma therapy.

We evaluated localization of angiotensin-converting enzyme 2 (ACE2), the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the salivary and associated tissues using immunohistochemistry. Fifty paraffin-embedded blocks from 48 anonymized patients, biopsied or operated on for diseases of the oral and maxillofacial region before 2010, were analyzed. ACE2-expressing cells were observed in the parotid, sublingual and the buccal glands, the conduits, the acinar regions of the serous glands, and sparsely in the mucous glands. Scattered ACE2-positive endothelial cells were also observed in nearby capillaries nourishing the salivary glands, as well as in the juxta-epithelial capillaries of the oral mucosa. ACE-2-positive adipocytes were scattered within the stroma of the parotid gland. These observations suggest the possibility that SARS-CoV-2 may travel through the bloodstream to the capillaries that nourish the salivary glands and oral mucosa, and inducing vasculitis and damage of oral tissues. SARS-CoV-2 infection of salivary glands through the bloodstream implies the main cause of salivary contamination. Similarly, ascending infection from oral fluid to the salivary gland conduit has been shown to be another possible route. Moreover, infection of ACE2-positive parotid adipocytes may lead to parotid glands inflammation and contribute to systemic progression of coronavirus disease 2019.

The elevated expression of Cell cycle-Related and Expression-elevated Protein in Tumor (CREPT) is reported to promote the growth of several tumors by enhancing Wnt/β-catenin signaling and cell cycle. However, the relevance of CREPT to the malignancy of salivary gland adenoid cystic carcinoma (SACC) remains unclear. The samples from 51 SACC patients were exploited in this study. We found that SACC samples exhibited a noticeably robuster CREPT expression than the para-cancerous tissues. Statistical analysis suggested that CREPT expression was significantly correlated with the T classification of SACC. To up- or down-regulating CREPT expression, the specific shRNA or full length of CREPT was delivered into SACC cell lines to examine the cell proliferation, migration, colony formation and implanted xenograft survival. Western blot assay and immunohistochemistry were applied to evaluate the expression of CREPT, cyclin D1, c-Myc and CDK4. Up-regulated CREPT in the low metastatic SACC line significantly promoted proliferation and colony formation, as well as cyclin D1, c-Myc and CDK4 expression. While knocking down of CREPT in the high metastatic SACC line remarkably reduced above effects. Furthermore, the SACC xenograft in mice confirmed that down-regulation of CREPT inhibited the in vivo tumor growth. Our study indicated that the elevated CREPT expression promoted the cell proliferation and tumor size of SACC by enhancing the expression of cyclin D1, c-Myc and CDK4, suggesting that CREPT contributed to SACC progression by stimulating cell proliferation, and might act as a potential target in future SACC therapy.

This study aimed to explore the expression and clinicopathological significance of CTAs MAGE-1, NY-ESO-1, MAGE-C2 and SCP-1 in adenoid cystic carcinoma (ACC). Immunohistochemistry was used to detect their expressions in 70 cases of ACC, and in 6 healthy tumor-adjacent salivary glands. The correlation between the expressions of the four CTAs, clinical and pathological features, and patients’ overall survival (OS) were analyzed. Of the 70 ACC cases, strong staining was observed in 43 (61.4%) for MAGE-1, 14 (20%) for NY-ESO-1, 9 (12.9%) for SCP-1, and 6 (8.6%) for MAGE-C2. We also found some significant correlations between the CTAs expression and clinicopathological parameters, for example, MAGE-1 and tumor size, NY-ESO-1 and distant metastasis, MAGE-C2 and tumor site, SCP-1 and age, SCP-1 and histopathological types (P < 0.05). Patients with any single CTAs positive staining showed a similar OS compared to those with negative staining, however patients with strong expression (score 6-7) of MAGE-C2 showed a significantly reduced OS compared to those scored 0-5 (P < 0.05). There was no OS difference between patients expressing simultaneously any 2 of the 4 CTAs and those with negative expression or those expressing only one of the 2 CTAs. Similar results were found in patients expressing at least 3 CTAs compared with patients expressing less than 3 CTAs. However, patients with the four CTAs co-expression had a substantially reduced mean survival time of 131.8 months compared with 176.5 months in patients with at least one CTA negative (P < 0.05). In conclusion, a significant fraction of patients with ACC showed expression of MAGE-1, NY-ESO-1, MAGE-C2 and SCP-1, indicating these CTAs might represent potential antigens for cancer vaccines. In addition, MAGE-C2 may be an important prognostic marker of ACC.

Rosemary is used as an herb in cooking and aromatic oils, and has long been used as a medicinal herb because of its functional components. According to folklore, monks recommended a remedy of rosemary in alcohol (“Hungarian water”) to a Hungarian queen suffering from limb numbness, resulting in instant recovery and rejuvenation. This is why the queen married a 20-year-old king of Holland while in her seventies. In order to clarify the “rejuvenation” mechanisms of traditional Hungarian water, we examined the anti-oxidant activity, anti-glycation activity, inhibition of melanin production and suppression of tumor growth of ethanol extracts of rosemary in this study. It was found that the ethanol extract had high anti-oxidant activity, high anti-glycation activity, high inhibition of melanin production and high suppression of tumor cell growth.

To investigate the association of MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms with birth defects in southern Chinese population. Genotyping was performed by Fluorescence Quantitative Analyzer using the Sequencing Reaction Universal Kit. Association analysis method was used to explore the relationship between genetic polymorphisms in MTHFR, MTRR gene and birth defects. Our results showed that serum folic acid level of genotype TT in MTHFR C677T was significantly lower than other genotypes, while homocysteine level significantly higher compared with CC and CT (P < 0.05). In addition, genotype GG in MTRR A66G might also promote homocysteine accumulation (P < 0.05). Results of logistic regression represented that MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms were not important or independent risk factors for predicting birth defects. Besides, genotype distribution of MTHFR C677T was significantly different in normal and abnormal pregnancy population, and genotype TT might affect folic acid metabolism and promote homocysteine accumulation. However, MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms were not critical or independent risk factors for predicting birth defects in this study.

Reconstruction and augmentation of the alveolar bone defects pose a challenge for the dental surgeons due to its complex structure. The primary objective of tissue engineering is to regenerate or replace damaged tissues or organs including damaged bone tissues with bone grafts, cells, and biological molecules. 45S5-bioglass (45S5-BG), with its superior osteoconductive and osteoinductive abilities, has been at the forefront of tissue engineering, alveolar bone regeneration, and periodontal regenerative surgical procedures for the past several years. With the aim of regenerating supporting alveolar bone, 45S5-BG was synthesized via sol-gel technique. 45S5-BG was characterized by X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM) analysis. In vitro bioactivity study was validated in simulated body fluid (SBF) and analysed by Fourier-Transform Infrared Spectroscopy (FTIR). In vitro cell compatibility was assessed by 3-(4,5-dimethylthyazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L929 cells. Further, in vivo alveolar bone regenerative potential of 45S5-BG bone graft was evaluated. XRD spectrum confirmed the formation of combeite crystalline phase after sintering. TEM images imparted ultra-structural features of the sample and proved the presence of a major crystalline phase embedded in a glassy matrix. In vitro bioactivity study proved the formation of hydroxy carbonate apatite (HCA) as confirmed by FTIR analysis. The in vitro MTT assay results confirmed the cell compatibility of 45S5-BG and histological analysis proved new bone formation. Within the limitations of this study, the results demonstrated that in addition to the observed bioactive and cell compatible properties, sol-gel synthesized 45S5-BG bone graft exhibited notable alveolar bone regenerative potential.

This study aimed to summarize the clinicopathological findings and assess the immunophenotypes for undifferentiated pleomorphic sarcoma of soft tissue with multinucleated giant cells (UPS-ST-MGCs). We retrospectively identified five cases of UPS-ST-MGCs between 2010 and 2020, and evaluate histological and immunohistochemical findings using osteogenic markers, which were receptor activator of nuclear factor-kappa B ligand (RANKL), runt-related transcription factor 2 (RUNX2), and special AT-rich sequence-binding protein 2 (SATB2). Cases were divided into two types, based on the distribution of multinucleated giant cells (MGCs), as diffusely (MGCs diffuse type) or focally scattering (MGCs focal type). One out of five cases was classified as MGCs diffuse type and comprised relatively monotonous proliferation of atypical spindle cells widely expressing RANKL, RUNX2, and SATB2. This case showed aggressive clinicopathological features, such as a rapidly growing tumor with a high maximum standardized uptake value, high Ki-67 labeling index, and early postoperative recurrence, which can be called malignant giant cell tumor (GCT-ST). Conversely, the other four cases of the MGCs focal type were focally positive for RANKL, and negative for RUNX2 and STAB2, which appeared to be consistent with conventional features of undifferentiated pleomorphic sarcoma of soft tissue. Our results indicate that malignant GCT-ST can be included in UPS-ST-MGCs. Therefore, it is important to note its aggressive malignant characteristics and osteogenic differentiation. Osteogenic immunohistochemical examinations should be considered for UPS-ST-MGCs to confirm an accurate diagnosis and provide appropriate treatment.

Fluoride has recently been indicated as a risk factor for peri-implantitis. However, no reports have confirmed this intraorally in humans or in experiments using large animals. Thus, in the present study, we used beagles to verify the effects on surrounding tissue when dental implants were implanted and peri-implantitis was induced. To elucidate any possible correlation with peri-implantitis, we also quantitatively examined titanium corrosion and elution due to fluoride. subjects were divided into three groups, namely, (1) no fluoride, no pressure thread; (2) fluoride, no pressure thread; and (3) fluoride, pressure thread. All the total 12 implants survived, indicating an implant survival rate of 100%. Dental X-ray measurement of bone resorption and measurement of bone destruction volume with μCT indicated significantly more bone resorption and bone destruction in group (3) than in group (1). There was no significant difference between group (1) and group (2). in addition, there was no significant difference between group (2) and group (3). Scanning electron microscope measurement of titanium in gingiva around the implants did not reveal any significant differences among the three groups. Based on quantitative data, our results suggested that fluoride exacerbates peri-implantitis.

Bisphosphonate (BP) formulations are drugs that improve bone strength by suppressing osteoclast activation, preventing fractures of the vertebrae and the femoral head, but their side effects include osteonecrosis of the jaw (ONJ). In this case it is known as medication-related osteonecrosis of the jaw (MRONJ), and pathological and microbiological investigations have suggested that infection is one major causative factor. However, many points regarding the etiology of ONJ and its causative factors remain unclear. In this study, we administered BP to model mice and exposed their jaws to bacterial infection to produce a mouse model of BRONJ, and analyzed their bone structure, including an analysis of the quality of bone surrounding extraction cavities. We found that mice not exposed to bacterial infection did not develop ONJ, and that those mice exposed to bacterial infection that did develop ONJ exhibited abnormal collagen fiber arrangement and poor bioapatite crystal alignment. An analysis of areas of bone surrounding poorly healed extraction cavities also revealed that its quality was poor. These results showed that although BP use increases bone mineral density, it reduces the alignment of collagen fibers and decreases bone quality. Zoledronate (Zol) alone resulted in epithelial healing, but reduced bone quality. In addition, it was suggested that bacterial infection could develop into a condition similar to BRONJ.