IL-8 activates fibroblasts to promote the invasion of HNSCC cells via STAT3-MMP1.

Matrix metalloproteinase-1 (MMP1) has an aberrant expression relevant to various behaviors of cancers. As dominant components of the tumor stroma, fibroblasts constitute an important source of Matrix metalloproteinase (MMPs) including mainly MMP1. The impacts of MMP1 derived from fibroblasts in tumor microenvironment, however, is not well defined. In this study, we demonstrated a part of crosstalk between fibroblasts and cancer cells that enhanced the invasiveness of cancer cells, IL8-induced activation of STAT3 signaling pathway as a key promoter to elevated MMP1 level in fibroblasts that supports the migration and invasion of head and neck squamous cell carcinoma (HNSCC) cells by extracellular matrix degradation. Importantly, once exposed to the inhibitor of STAT3 phosphorylation (TPCA-1), the enhanced induction of HNSCC cells invasion triggered by fibroblasts was significantly impaired.

The Association Between Vitamin D and Early Childhood Caries: A Systematic Review and Meta-Analysis.

PURPOSE: Previous surveys have reported that children with vitamin D deficiency were likely to suffer from early childhood caries (ECC). The aim of this systematic review and meta-analysis was to determine 1. whether the status of vitamin D is intrinsically related to the occurrence of ECC and 2. the optimal level of vitamin D for the prevention of ECC. MATERIALS AND METHODS: The database of PubMed, Web of Science, Cochrane, Embase and Google scholar were searched for targeted literature. The eligibility criteria were observational studies in which children with ECC were compared to children without ECC in terms of their vitamin D status. Applying the Newcastle-Ottawa tool, study selection, data extraction, and risk of bias assessment were performed by 2 reviewers independently. Meta-analysis was performed using the Cochrane Collaboration's Review Manager 5.4 software. RESULTS: 501 articles were retrieved from the electronic databases; 11 studies were finally included in systematic review, 10 studies of which were submitted to meta-analysis. The 25(OH)D levels in the ECC group were statistically significantly lower compared with that in the caries-free group (WMD = -13.96, 95% CI: [-19.88,-8.03], p < 0.001), especially in regard to the association between S-ECC and vitamin D (WMD = -18.64, 95% CI: [-20.06,-17.22], p < 0.001). The subgroup analyses in terms of geographical region demonstrated that children with a level of 25(OH)D of 50-75 nmol/l were more likely to have ECC than those with over 75 nmol/l (OR = 1.42, 95% CI: [1.26,1.60], p < 0.001), with data from Asia and Europe combined for analysis Conclusions: The level of vitamin D was lower in children with ECC than in caries-free children, and the correlation between S-ECC and vitamin D was even stronger. The optimal 25(OH)D level for preventing occurrence and development of ECC was ≥ 75 nmol/l. Thus, clinicians should view the development of early caries also from a systemic perspective.

WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling.

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-ß-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

A 3-year follow-up clinical study on the preservation for vitality of involved tooth in jaw cysts through an innovative method.

Jaw cysts commonly affect the oral and maxillofacial region, involving adjacent tooth roots. The management of these teeth, particularly regarding root canal therapy and apicoectomy, lacks consensus. This study introduces a novel treatment concept and refined surgical approach to preserve pulp viability in teeth involved in jaw cysts. The objective was to investigate the effectiveness and potential benefits of this approach over a 36-month follow-up period. A conservative management approach prioritized vitality preservation, reserving root canal treatment and apicectomy for cases with post-operative discomfort. A comprehensive follow-up of 108 involved teeth from 36 jaw cyst cases treated with the modified method was conducted. Clinical observation, X-ray imaging, cone-beam computed tomography (CBCT), and pulp vitality testing assessed changes in cyst size, tooth color, pulp vitality, root structure, and surrounding alveolar bone. After 36 months, our modified surgical approach successfully preserved tooth vitality in 84 involved teeth. Adverse symptoms in 19 teeth, such as redness, swelling, fistula, and pain, resolved with postoperative root canal therapy. Follow-up was lost for five teeth in two cases. No cyst recurrences were observed, and in 34 cases, the bone cavity gradually disappeared, restoring normal bone density during long-term follow-up. Our modified surgical method effectively preserves tooth vitality in jaw cysts. This innovative approach has the potential to improve the management of teeth involved in jaw cysts.

Regulation of the Notch signaling pathway by natural products for cancer therapy.

The Notch signaling pathway is an evolutionarily conserved pathway that modulates normal biological processes involved in cellular differentiation, apoptosis, and stem cell self-renewal in a context-dependent fashion. Attributed to its pleiotropic physiological roles, both overexpression and silencing of the pathway are associated with the emergence, progression, and poorer prognosis in various types of cancer. To decrease disease incidence and promote survival, targeting Notch may have chemopreventive and anti-cancer effects. Natural products with profound historical origins have distinguished themselves from other therapies due to their easy access, high biological compatibility, low toxicity, and reliable effects at specific physiological sites in vivo. This review describes the Notch signaling pathway, particularly its normal activation process, and some main illnesses related to Notch signaling pathway dysregulation. Emphasis is placed on the effects and mechanisms of natural products targeting the Notch signaling pathway in diverse cancer types, including curcumin, ellagic acid (EA), resveratrol, genistein, epigallocatechin-3-gallate (EGCG), quercetin, and xanthohumol and so on. Existing evidence indicates that natural products are feasible solution to fight against cancer by targeting Notch signaling, either alone or in combination with current therapeutic agents.

Exploring the Role of Wnt Ligands in Osteogenic Differentiation of Human Periodontal Ligament Stem Cells.

OBJECTIVES: This study aimed to investigate the functions of 19 types of Wnt ligands during the process of osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs), with particular attention to WNT3A and WNT4. MATERIALS AND METHODS: The expression levels of 19 types of Wnt ligands were examined using real-time quantitative polymerase chain reaction (real-time qPCR) during hPDLSCs osteogenic differentiation at 7, 10, and 14 days. Knockdown of WNT3A and WNT4 expression was achieved using adenovirus vectors, and conditioned medium derived from WNT3A and WNT4 overexpression plasmids was employed to investigate their roles in hPDLSCs osteogenesis. Osteogenic-specific genes were analyzed using real-time qPCR. Alkaline phosphatase (ALP) and alizarin red S activities and staining were employed to assess hPDLSCs' osteogenic differentiation ability. RESULTS: During hPDLSCs osteogenic differentiation, the expression of 19 types of Wnt ligands varied, with WNT3A and WNT4 showing significant upregulation. Inhibiting WNT3A and WNT4 expression hindered hPDLSCs' osteogenic capacity. Conditioned medium of WNT3A promoted early osteogenic differentiation, while WNT4 facilitated late osteogenesis slightly. CONCLUSION: Wnt ligands, particularly WNT3A and WNT4, play an important role in hPDLSCs' osteogenic differentiation, highlighting their potential as promoters of osteogenesis. CLINICAL RELEVANCE: Given the challenging nature of alveolar bone regeneration, therapeutic strategies that target WNT3A and WNT4 signaling pathways offer promising opportunities. Additionally, innovative gene therapy approaches aimed at regulating of WNT3A and WNT4 expression hold potential for improving alveolar bone regeneration outcomes.

Plant-derived nanovesicles: harnessing nature's power for tissue protection and repair.

Tissue damage and aging lead to dysfunction, disfigurement, and trauma, posing significant global challenges. Creating a regenerative microenvironment to resist external stimuli and induce stem cell differentiation is essential. Plant-derived nanovesicles (PDNVs) are naturally bioactive lipid bilayer nanovesicles that contain proteins, lipids, ribonucleic acid, and metabolites. They have shown potential in promoting cell growth, migration, and differentiation into various types of tissues. With immunomodulatory, microbiota regulatory, antioxidant, and anti-aging bioactivities, PDNVs are valuable in resisting external stimuli and facilitating tissue repair. The unique structure of PDNVs provides an optimal platform for drug encapsulation, and surface modifications enhance their stability and specificity. Moreover, by employing synergistic administration strategies, PDNVs can maximize their therapeutic potential. This review summarized the progress and prospects of PDNVs as regenerative tools, provided insights into their selection for repair activities based on existing studies, considered the key challenge for clinical application, and anticipated their continued prominent role in the field of biomedicine.

Treatment outcomes of regenerative endodontic procedures in nonvital mature permanent teeth: a retrospective study.

OBJECTIVES: This retrospective study was undertaken to clinically and radiographically evaluate the long-term outcomes of regenerative endodontic procedures (REPs) for nonvital mature permanent teeth, to analyze predictors influencing treatment outcomes. METHODS: Nonvital mature permanent teeth treated by REPs with a minimum follow-up period of 6 months were included from 2015 to 2017. Treatment outcomes were categorized as success and failure. The periapical status and lesion healing were assessed in terms of the periapical index (PAI) and the percentage changes in periapical radiolucency (PARL) area. The clinical and radiographic outcomes of REPs were assessed by Mann-Whitney test at different follow-up period. Kaplan-Meier curves and Univariate Cox regression analysis were conducted to assess the success and identify potential predictors affecting outcomes, respectively. RESULTS: A total of 37 mature teeth with an average follow-up of 4.3 years satisfied the criteria, and 89.2% of the teeth had a successful outcome. Significant differences in PAI scores were found between each period with respect to the baseline (p < .05). Among different periods, there was a significant difference between intervals of 3-6 months and 7-12 months (p = .039) and no significant difference between each interval of more than 12 months (p > .05). Eighty-seven percent of teeth with preoperative PARL presented completely healed. REPs significantly decreased the PARL area at the interval of 7-12 months compared to 3-6 months (p = .025), with no significant difference between each interval of more than 12 months (p > .05). No significant predictor was found for the success of outcome (p > .05). Thirteen teeth (35.1%) regained pulp sensibility, and 40.5% of the teeth exhibited intracanal calcification. CONCLUSIONS: Within the limitations of this study, REPs provided a high long-term success rate and promoted the resolution of PARL as a biologically-based alternative treatment option for nonvital mature teeth. CLINICAL RELEVANCE: REPs provide a high long-term success rate and promoted healing of apical periodontitis comparable with reported outcomes for root canal therapy of mature teeth.

Engineered Plant-Derived Nanovesicles Facilitate Tumor Therapy: Natural Bioactivity Plus Drug Controlled Release Platform.

Tumors are the second-most common disease in the world, killing people at an alarming rate. As issues with drug resistance, lack of targeting, and severe side effects are revealed, there is a growing demand for precision-targeted drug delivery systems. Plant-derived nanovesicles (PDNVs), which arecomposed of proteins, lipids, RNA, and metabolites, are widely distributed and readily accessible. The potential for anti-proliferative, pro-apoptotic, and drug-resistant-reversing effects on tumor cells, as well as the ability to alter the tumor microenvironment (TME) by modulating tumor-specific immune cells, make PDNVs promising anti-tumor therapeutics. With a lipid bilayer structure that allows drug loading and a transmembrane capacity readily endocytosed by cells, PDNVs are also expected to become a new drug delivery platform. Exogenous modifications of PDNVs enhance their circulating stability, tumor targeting ability, high cell endocytosis rate, and controlled-release capacity. In this review, we summarize PDNVs' natural antitumor activity, as well as engineered PDNVs as efficient precision-targeted drug delivery tools that enhance therapeutic effects. Additionally, we discuss critical considerations related to the issues raised in this area, which will encourage researchers to improve PDNVs as better anti-tumor therapeutics for clinic applications.

Application Study of Novel Eggshell/Ag Combined with Pit and Fissure Sealants.

Objective: The study aims to enhance the anti-caries performance of pit and fissure sealants through the synthesis of novel silver nanocomposites, and to evaluate their mechanical properties and biological safety in vitro and in vivo. Methods: The antibacterial properties of synthetic eggshell/Ag were detected by bacterial inhibition zone, minimum bacteriostatic concentration, fluorescence staining and scanning electron microscopy. The synthetic products were then combined with pit and fissure sealants to prepare specimens, and their effects on mechanical properties, antibacterial properties and cytotoxicity were evaluated. Furthermore, an oral mucosal contact model of golden hamsters was established according to the ISO10933 standard to evaluate local stimulation and systemic effects. Results: The novel nanocomposite eggshell/Ag was confirmed to exhibit strong broad-spectrum antibacterial activity, and that the eggshell/Ag-modified pit and fissure sealant had strong antibacterial properties against common dental caries bacterial biofilms, without any significant change in mechanical properties. The gradient dilution extract showed acceptable cytotoxicity, and in the golden hamster oral contact model, there were no visible abnormalities in local mucosal tissues, blood indices, or liver and kidney histopathology. Conclusions: These findings suggest that eggshell/Ag combined with pit and fissure sealants has strong antibacterial activity and excellent biosafety in vitro and in vivo, making it a promising candidate for clinical applications.

CDH4 inhibits ferroptosis in oral squamous cell carcinoma cells.

BACKGROUND: The cadherin-4 gene (CDH4), a member of the cadherin family genes, encodes R-cadherin (R-cad); however, the function of this gene in different types of cancer remains controversial. The function of CDH4 in OSCC (oral squamous cell carcinoma) is unknown. MATERIALS AND METHODS: We use the Cancer Genome Atlas (TCGA) database to find the expression of CDH4 in OSCC is more than normal tissue. Our tissue samples also confirmed that CDH4 gene was highly expressed in OSCC. The related cell function assay detected that CDH4 promotes the ability of cell proliferation, migration, self-renewal and invasion. Cell staining experiment confirmed that the change of CDH4 expression would change the cell mortality. The western blot of GPX4 (glutathione-dependent peroxidase-4), GSH (reduced glutathione) test assay and MDA(Malondialdehyde) test assay show that the expression of CDH4 may resist the sensitivity of ferropotosis in OSCC. RESULTS: CDH4 was upregulated in OSCC samples and was correlation with poor survival of patients. High expression of CDH4 effectively promotes the proliferation, mobility of OSCC cells and reduce the sensitivity of OSCC cells to ferroptosis. CDH4 is positively correlated with EMT pathway genes, negatively correlated with fatty acid metabolism pathway genes and peroxisome pathway genes, and positively correlated with ferroptosis suppressor genes in OSCC. CONCLUSIONS: These results indicate that CDH4 may play a positive role in tumor progression and resistance ferroptosis and may be a potential therapeutic target for OSCC.

Clinical and radiographic outcomes of regenerative endodontic procedures for traumatized permanent necrotic teeth with apical periodontitis and external root resorption.

AIM: This clinical study was undertaken to assess the effect of treatment with regenerative endodontic procedures (REPs) on 20 teeth with pulp necrosis, apical periodontitis, and external root resorption (ERR). METHODOLOGY: Teeth were treated with REPS utilizing the American Association of Endodontists (AAE) protocol. Quantitative assessment of changes in radiographic root area (RRA) were statistically analysed to assess changes in root dimensions after an average follow-up period of 3 years. RESULTS: All 20 teeth survived, 14 teeth (70%) were classified successful, and only 1 tooth (5%) failed throughout the study period. Based on the radiographic examination, all 20 teeth showed complete repair of the periapical lesions and arrested ERR. However, 5 teeth (25%) subsequently developed replacement resorption. The RRA between baseline and 3-year follow-up showed a significant difference for the total 20 teeth (p = .009). An analysis according to the trauma type and the extra-oral time showed the RRA increase was significantly different in the non-avulsion group (p = .015) and for the avulsion group with an extra-oral time less than 60 min (p = .029). The RRA increase was not statistically significant in the avulsion group of extra-oral time more than 60 min (p = .405). Nine teeth (45%) and 10 teeth (50%) responded to cold and electric pulp testing, respectively. CONCLUSIONS: Within the limitations of this study, the favourable outcomes of REPs were further confirmed for traumatized permanent necrotic teeth with ERR in terms of periapical lesion healed and a significant increase in RRA. The study contributes further evidence of the role of REPs in arresting ERR.

Splenic infarction during acute falciparum malaria: A case report.

Splenomegaly is common in malaria, but splenic infarction is a rare complication of malaria. We report a case of a patient with Plasmodium falciparum infection who developed abdominal pain, reappearance of fever, elevated D-dimer during treatment, and abdominal CT confirmed splenic infarction. The abdominal pain was relieved and the fever subsided by analgesic and anticoagulant therapy. Six months later, abdominal CT showed splenic recovery. As a result, splenic infarction should be considered when a patient with malaria developed abdominal pain, reappearance of fever and elevated blood D-dimer during treatment. In the absence of surgical indications, conservative medical treatment is effective.

FAT1 Upregulates in Oral Squamous Cell Carcinoma and Promotes Cell Proliferation via Cell Cycle and DNA Repair.

Objective: Previous studies have revealed that FAT atypical cadherin 1 (FAT1) plays a tumor-suppressive or oncogenic role in a context-dependent manner in various cancers. However, the functions of FAT1 are ambiguous in tumorigenesis owing to inconsistent research in oral squamous cell carcinoma (OSCC). The present study aimed at gaining an insight into the role of FAT1 in the tumor genesis and development. Methods: The expression, mutant, and survival data analyses were done using data from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database, verified with clinical samples via real-time polymerase chain reaction (qRT-PCR), Western blot (WB), and immunohistochemical (IHC) staining. OSCC cells transfected with siRNA were employed for in vitro assessment in cell proliferation, apoptosis, and migration ability in appropriate ways. The underlying mechanism was explored by RNA sequencing after FAT1 silencing. Results: Overall, FAT1 significantly increased in OSCC with a poor prognosis outcome. The in vitro experiment showed the promoting effect of FAT1 in the proliferation and migration of OSCC cells. FAT1 can also inhibit both the early and late apoptosis of OSCC cells. RNA-sequencing analysis of FAT1 silencing revealed that the cell cycle, DNA replication, and some core genes (MCM2, MCM5, CCNE1 SPC24, MYBL2, KIF2C) may be the potential mechanism in OSCC. Conclusions: FAT1 may act as an oncogene in OSCC with potential mechanism influencing the cell cycle and DNA repair.

Mechanical stress reduces secreted frizzled-related protein expression and promotes temporomandibular joint osteoarthritis via Wnt/ß-catenin signaling.

AIMS: Mechanical stress overload in the temporomandibular joint (TMJ) is an important cause of TMJ osteoarthritis (TMJOA). Whether secreted frizzled-related proteins (SFRPs) play important roles in the development of mechanical stress-induced TMJOA remains controversial. In this study, we investigated the roles of the Wnt/ß-catenin signaling and SFRPs in the progression of mechanical stress-induced TMJOA. METHODS: We investigated the progression of mechanical stress-induced TMJOA using an in vivo model via modified increased occlusal vertical dimension (iOVD) malocclusion and an in vitro model in which isolated chondrocytes were subjected to mechanical stress. The effects of inhibition of Wnt/ß-catenin signal on TMJOA induced by mechanical stress were studied by in vitro drug added and in vivo intra-articular injection of XAV-939. TMJOA progression, Wnt/ß-catenin signaling and SFRPs was assessed by Cone beam computed tomography (CBCT) analysis, histochemical and immunohistochemical (IHC) staining, quantitative real-time PCR (qRT-PCR), Western blotting (WB), and immunofluorescence (IF) staining. RESULTS: Our in vivo results showed that iOVD-induced mechanical stress in the TMJ disrupted mandible growth, induced OA-like changes in TMJ cartilage, and increased OA-related cytokine expression. In addition, iOVD activated Wnt/ß-catenin signaling and suppressed Sfrp1, Sfrp3, and Sfrp4 expression in condylar cartilage. Moreover, our in vitro study showed that stress disrupted homeostasis, activated Wnt/ß-catenin signaling and inhibited SFRP3 and SFRP4 expression in chondrocytes. Suppression of Wnt/ß-catenin signaling with XAV-939 promoted SFRP3 and SFRP4 expression and rescued mechanical stress-induced cartilage degeneration in vivo and in vitro. CONCLUSIONS: Our work suggests that mechanical stress reduces SFRPs expression both in vivo and in vitro and promotes TMJOA via Wnt/ß-catenin signaling. Suppression of Wnt/ß-catenin signaling promotes SFRPs expression, especially SFRP3 and SFRP4 expression, and rescues mechanical stress-induced cartilage degeneration. Wnt/ß-catenin signaling and SFRPs may represent potential therapeutic targets for TMJOA.

Effects of functional mandibular lateral shift on craniofacial growth and development in growing rats.

BACKGROUND: Unilateral posterior crossbite, one of the most frequent malocclusions, is often associated with functional lateral shift of the mandible. Although the effects of functional lateral shift on the mandible and temporomandibular joint have been examined in various animal experiments, cranial and maxillary changes have received less attention. OBJECTIVE: The aim of this study was to investigate the effects of functional lateral shift on the craniofacial complex in growing rats. METHODS: Eighty 5-week-old male Sprague-Dawley rats were randomly divided into an experimental group (n = 40), which received an oblique guide appliance that shifted the mandible to the left during closure, and a control group (n = 40). The rats were scanned by cone-beam computed tomography at 3 days and 1, 2, 4 and 8 weeks. The dimensions of the mandibular bone, condyle, maxilla and cranium were measured. RESULTS: The mandibles of rats in the experimental group were smaller than those of the rats in the control group and were asymmetrical. The condyles of the rats in the experimental group were thinner than those of the control rats. The condylar length on the ipsilateral side was shorter and wider than that on the contralateral side from 4 to 8 weeks. No significant differences in cranial length or height were observed between the experimental and control groups. The height of the upper first molar and alveolar bone on the contralateral side was significantly smaller than that on the ipsilateral side and in the controls from 4 to 8 weeks. CONCLUSION: Functional shift in the mandible produces morphological asymmetries in the mandible and maxillary region and may cause bilateral condylar degenerative changes.

Integrin-Mediated Tumorigenesis and Its Therapeutic Applications.

Integrins, a family of adhesion molecules generally exist on the cell surface, are essential for regulating cell growth and its function. As a bi-directional signaling molecule, they mediate cell-cell and cell-extracellular matrix interaction. The recognitions of their key roles in many human pathologies, including autoimmunity, thrombosis and neoplasia, have revealed their great potential as a therapeutic target. This paper focuses on the activation of integrins, the role of integrins in tumorigenesis and progression, and advances of integrin-dependent tumor therapeutics in recent years. It is expected that understanding function and signaling transmission will fully exploit potentialities of integrin as a novel target for tumors.

Abnormal eruption of teeth in relation to FGFR1 heterozygote mutation: a rare case of osteoglophonic dysplasia with 4-year follow-up.

BACKGROUND: We report a case and its 4-year follow-up of Osteoglophonic dysplasia (OD), a rare disease that disturbs both skeletal and dental development, which is usually caused by heterozygous FGFR1 mutations. CASE PRESENTATION: This article presents a case where a 6-year-old male patient suffered dysregulation of tooth eruption and was diagnosed with osteogenic dysplasia from a fibroblast growth factor receptor 1 (FGFR1) heterozygote mutation. However, the number of teeth is within the normal range, and their roots are well developed. Several interventions were implemented with varying degrees of results. The details of the 4-year follow-up showed that the signs of OD were more pronounced, including dwarfism, frontal bossing, delayed skeletal maturation, anteverted nares, micrognathia, and prominent ears, but the patient's impacted teeth and edentulous jaws remained unchanged. CONCLUSIONS: FGFR1 heterozygote mutation and OD present significant difficulty for teeth eruption and subsequent intervention. Further measures ought to be taken in recognizing various symptoms presented by the patient. This case supports the significance of careful inquiry, comprehensive physical examination and correct diagnosis as indispensable steps for clinical practice in patients with unerupted teeth. Additionally, the detailed case and its 4-year follow-up length may provide new insights into osteogenic dysplasia and patients with impacted teeth while encouraging further exploration in treatment methods.

Experimental functional shift-induced osteoarthritis-like changes at the TMJ and altered integrin expression in a rat model.

Mandibular deviation affects the biomechanical environment of the temporomandibular joint (TMJ) and causes thinning of cartilage on the deviated side. We aimed to evaluate, using a rat model, the effect of mandibular functional deviation on the TMJ in relation to the functional roles of integrin ß family members. The effects of experimental functional deviation on the TMJ of 6-week-old Sprague-Dawley female rats, randomly assigned to control (n = 42) and experimental groups (n = 42), were evaluated at 3 days and 1, 2, 4, and 8 weeks by histological staining, immunofluorescence, real-time quantitative polymerase chain reaction, and micro-computed tomography. The results showed that the experimental functional shift changed the shape of condyles, thinned the cartilage, and increased the proportion of the hypertrophic layer on the deviated sides of condyles. In addition, the extracellular matrix of the condyle cartilage exhibited degradation at 1 week and subchondral trabecular bone was lost at 4 and 8 weeks. Osteoarthritis (OA)-like changes occurred in the left and right condyles of rats in the experimental group and were aggravated over time. Integrin ß family expression, especially integrin ß2 , was altered from week 1, possibly related to the OA-like changes. These data may provide insight into the onset of TMJ OA.

EGCG inhibits growth of tumoral lesions on lip and tongue of K-Ras transgenic mice through the Notch pathway.

Epigallocatechin-3-gallate (EGCG), the main active ingredient of green tea, exhibits low toxic side effect and versatile bioactivities, and its anti-cancer effect has been extensively studied. Most of the studies used cancer cell lines and xenograft models. However, whether EGCG can prevent tumor onset after cancer-associated mutations occur is still controversial. In the present study, Krt14-cre/ERT-Kras transgenic mice were developed and the expression of K-RasG12D was induced by tamoxifen. Two weeks after induction, the K-Ras mutant mice developed exophytic tumoral lesions on the lips and tongues, with significant activation of Notch signaling pathway. Administration of EGCG effectively delayed the time of appearance, decreased the size and weight of tumoral lesions, relieved heterotypic hyperplasia of tumoral lesions, and prolonged the life of the mice. The Notch signaling pathway was significantly inhibited by EGCG in the tumoral lesions. Furthermore, EGCG significantly induced cell apoptosis and inhibited the proliferation of tongue cancer cells by blocking the activation of Notch signaling pathway. Taken together, these results indicate EGCG as an effective chemotherapeutic agent for tongue cancer by targeting Notch pathway.