Chronic restraint stress promotes oral squamous cell carcinoma development by inhibiting ALDH3A1 via stress response hormone.

BACKGROUND: Chronic restraint stress (CRS) has iteratively been reported to be possibly implicated in the development of numerous cancer types. However, its role in oral squamous cell carcinoma (OSCC) has not been well elucidated. Here we intended to evaluate the role and mechanism. METHODS: The effects of CRS were investigated in xenograft models of OSCC by using transcriptome sequencing, LC-MS, ELISA and RT-PCR. Moreover, the role of CRS and ALDH3A1 on OSCC cells was researched by using Trans-well, flow cytometry, western blotting, immunofluorescence, ATP activity and OCR assay. Furthermore, immunohistochemical staining was employed to observe the cell proliferation and invasion of OSCC in xenotransplantation models. RESULTS: CRS promoted the progression of OSCC in xenograft models, stimulated the secretion of norepinephrine and the expression of ADRB2, but decreased the expression of ALDH3A1. Moreover, CRS changed energy metabolism and increased mitochondrial metabolism markers. However, ALDH3A1 overexpression suppressed proliferation, EMT and mitochondrial metabolism of OSCC cells. CONCLUSION: Inhibition of ALDH3A1 expression plays a pivotal role in CRS promoting tumorigenic potential of OSCC cells, and the regulatory of ALDH3A1 on mitochondrial metabolism may be involved in this process.

Comprehensive analysis of m6A modifications in oral squamous cell carcinoma by MeRIP sequencing.

N6-methyladenosine (m6A) modifications are the most abundant internal modifications of mRNA and have a significant role in various cancers; however, the m6A methylome profile of oral squamous cell carcinoma (OSCC) in the mRNA-wide remains unknown. In this study, we examined the relationship between m6A and OSCC. Four pairs of OSCC and adjacent normal tissues were compared by Methylated RNA immunoprecipitation sequencing (MeRIP-seq). Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Ingenuity Pathway Analysis (IPA) analyses were used to further analyze the MeRIP-seq data. A total of 2,348 different m6A peaks were identified in the OSCC group, including 85 m6A upregulated peaks and 2,263 m6A downregulated peaks. Differentially methylated m6A binding sites were enriched in the coding sequence in proximity to the stop codon of both groups. KEGG analysis revealed genes with upregulated m6A-modified sites in the OSCC group, which were prominently associated with the forkhead box O (FOXO) signaling pathway. Genes containing downregulated m6A-modified sites were significantly correlated with the PI3K/Akt signaling pathway, spliceosome, protein processing in the endoplasmic reticulum, and endocytosis. IPA analysis indicated that several genes with differential methylation peaks form networks with m6A regulators. Overall, this study established the mRNA-wide m6A map for human OSCC and indicated the potential links between OSCC and N6-methyladenosine modification.

Chronic restraint stress promotes the tumorigenic potential of oral squamous cell carcinoma cells by reprogramming fatty acid metabolism via CXCL3 mediated Wnt/ß-catenin pathway.

Chronic stress promotes tumor progression and may harm homeostasis of energy metabolism by disrupting key metabolic processes. Recently, emerging evidence that chemokines CXCL3 as a novel adipokine plays a new role in lipid metabolism and various human malignancies. However, the role and mechanism of the CXCL3 in oral squamous cell carcinoma (OSCC) progression and reprogramming lipid metabolism induced by chronic restraint stress is unclear. The analysis of transcriptome sequencing, LC-MS, GC-MS, CCK8, cell apoptosis assays, cell cycle analysis, qRT-PCR, ELISA, western blotting, immunofluorescence, immunohistochemistry, RNA interference and lentivirus transfection and a xenograft tumor growth and chronic restraint stress model were used to investigate the role of CXCL3 in the regulation of lipid metabolism and OSCC and explore the underlying molecular mechanisms. We showed that CXCL3 plays a critical role in in fatty acid de novo synthesis and tumor growth induced by chronic restraint stress. We demonstrated that chronic restraint stress promoted lipid accumulation, OSCC growth and metastasis in a mouse xenograft model. CXCL3 knockdown and FH535, an inhibitor of Wnt/ß-catenin pathway, could attenuate fatty acid de novo synthesis, cell proliferation and epithelial-mesenchymal transition induced by chronic restraint stress in OSCC cells. Our findings demonstrate that chronic restraint stress promotes the proliferation and metastasis of OSCC by reprogramming fatty acid metabolism via CXCL3 mediated Wnt/ß-catenin pathway. Our study provides novel insights to help understand the underlying mechanisms of CXCL3 in OSCC progression induced by chronic restraint stress.

Clinical study on the posterior occlusal plane and morphology of temporomandibular joint / Estudio clínico sobre el plano oclusal posterior y la morfología de la articulación temporomandibular

The objective of the study was to investigate the morphological features of the temporomandibular joint in adult patients with posterior occlusal plane and different inclinations. Fifty five skeletal I occlusion patients with average were included, shooting CBCT in the intercuspal position, divided into 3 groups according to OPP-FH angle, and measurement of the temporomandibular joint morphology was calculated with cone beam computed tomography (CBCT) special software Invivo 5.0, Statistical analysis of three groups of data using SPSS23.0. The condyle usually locates in the middle of the fossa, the maximum axial area of the condyle (A) was statistically significant between the group 1 and the group 3. The internal and external diameter (MD) of the condyle was statistically significant between group 1 and group 3, and group 2 and group 3. The bilateral TMJ morphological features of the three groups were basically symmetrical. The position of the condyle in the fossa is mostly centered, and some of the posterior, the maximum axial area and the internal and external diameter of the condyle are different in three groups.

El objetivo de este estudio fue investigar las características morfológicas de la articulación temporomandibular (ATM) en pacientes adultos con plano oclusal posterior y diferentes inclinaciones. Se incluyeron 55 pacientes con oclusión esquelética tipo I, visualizados por tomografía computarizada de haz cónico (CBCT) en posición intercuspiana, y se dividieron en 3 grupos según el ángulo OPP-FH. La medición morfológica de la articulación temporomandibular se calculó con CBCT y mediante el software especial Invivo 5.0. El análisis estadístico de datos se realizó con el software SPSS 23.0. El cóndilo de la mandíbula generalmente se ubica en el centro de la fosa; el área axial máxima del cóndilo de la mandíbula (A) fue estadísticamente significativa entre los grupos 1 y 3. Los datos de los diámetros medial y lateral (DM) del cóndilo de la mandíbula fueron estadísticamente significativos entre los grupos 1 y 3 y los grupos 2 y 3. Las características morfológicas de la ATM de los tres grupos fueron básicamente simétricas. La posición del cóndilo de la mandíbula en la fosa fue principalmente centrada, y parte del área axial máxima, posterior y los diámetros medial y lateral del cóndilo de la mandíbula fueron diferentes en los tres grupos.

Expression of Ihh signaling pathway in condylar cartilage after bite-raising in adult rats.

Temporomandibular joint osteoarthritis (TMJOA) is a complex inflammatory condition with multiple factors and degenerative processes co-occurring. However, its pathogenesis remains uncertain. The purpose of the study was to observe the expression of Indian hedgehog (Ihh) signal related molecules in TMJOA induced by bite-raising and to study the effect and mechanism of Ihh signaling. Our research indicated that Ihh signaling pathway can be activated in condylar cartilage induced by bite-raising. The histological analysis showed TMJOA-like structural changes of condylar cartilage in experiment groups. Ihh, Smoothened (Smo), and Gli zinc finger transcription factors-1 (Gli-1) were activated in the experimental groups, and the expression levels increased significantly over time, whereas the sham control groups showed no fluctuation. Additionally, the expression levels of matrix metalloproteinase-13 (MMP-13) and cysteinyl aspartate specific proteinase-3 (Caspase-3) in the experiment groups increased in a time-dependent manner compared with the matched sham control groups. In conclusion, our results indicated that the Ihh signaling pathway may activate the occurrence of TMJOA by mediating the hypertrophy of chondrocytes, which may be an important regulatory mechanism and potential therapeutic target in the repair of condylar cartilage.

Biomechanical analysis of micro-implants lingual straight wire appliance during retracting maxillary anterior teeth / Análisis biomecánico de microimplantes con dispositivo de alambre recto lingual durante la retracción de dientes maxilares anteriores

This study aimed to establish three-dimensional finite element models of micro-implants-lingual straight wire appliance and to investigate the effects of different wire patterns on the initial displacement of the maxillary anterior teeth and the stress of the periodontal ligament and tooth root during retracting maxillary anterior teeth in lingual orthodontics. A three-dimensional geometric models of maxilla with maxillary dentition was established using Cone-beam CT scan .Three types of maxilla models including microimplants and Duet-Slot Lingual Bracket appliance with three different arch wires ( model A: 0.016 inch × 0.022 inch stainless steel square wire; modelB: 0.016 inch stainless steel round wire; model C: double wire of 0.016 inch × 0.022 inch stainless steel square wire + anterior teeth 0.016 inch stainless steel round wire) were assembled by Unigraphics NX 8.5 software. The labial intrusion force and lingual retraction force were simulatively loaded to obtain initial displacement of the anterior teeth and the stresses of each tooth root and periodontal ligament, using three-dimensional finite element calculation software Ansys Workbench 15. The initial displacement of the lateral incisors was close to the bodily movement; and central incisors and lateral incisors slightly extruded. Compared with group A and group C, canine teeth appeared obviously horizontal "arched effect" by crown labial tipping in group B. The stress distribution of the tooth root and periodontal ligament was minimal and uniform in the group C. The 0.016 × 0.022- in stainless steel rectangular wire combined with 0.016- in stainless steel round wire used in the anterior teeth can better control the torque of the maxillary anterior teeth for space close in lingual orthodontics. Moreover, the stress distribution of tooth root and periodontal ligament is even, which is difficult to damage the periodontal ligament or result in external resorption of tooth root.

Este estudio tuvo como objetivo establecer modelos tridimensionales de elementos finitos de microimplantes linguales de alambre recto e investigar los efectos de diferentes patrones de alambre en el desplazamiento inicial de los dientes maxilares anteriores y el estrés del ligamento periodontal y la raíz del diente durante la retracción lingual sobre los dientes anteriores del hueso maxilar en ortodoncia. Se establecieron modelos geométricos tridimensionales del hueso maxilar con dentición utilizando una exploración por tomografía computarizada de haz cónico. Tres tipos de modelos maxilares, incluidos los microimplantes y el dispositivo Duet-Slot Lingual Bracket con tres arcos diferentes (modelo A: 0.016 pulgada × 0.022 pulgada alambre cuadrado de acero inoxidable; modelo B: alambre redondo de acero inoxidable de 0.016 pulgadas; alambre cuadrado de acero inoxidable de 0.016 pulgada × 0.022 pulgada y alambre redondo de acero inoxidable de 0.016 pulgada) ensamblados por el software Unigraphics NX 8.5. La fuerza de intrusión labial y la fuerza de retracción lingual se cargó simultáneamente, para obtener el desplazamiento inicial de los dientes anteriores y las tensiones de cada raíz dental y ligamento periodontal, usando el software tridimensional de cálculo de elementos finitos Ansys Workbench 15. El desplazamiento inicial de los incisivos laterales se relacionaba al movimiento corporal; mientra que los incisivos centrales e incisivos laterales se mostraron ligeramente extruidos. Comparado con el grupo A y el grupo C, los dientes caninos presentaron un "efecto arqueado" horizontal por la inclinación labial de la corona en el grupo B. La distribución del estrés de la raíz del diente y el ligamento periodontal fue mínima y uniforme en el grupo C. El alambre rectangular de acero inoxidable combinado con el alambre redondo de acero inoxidable de 0.016 usado en los dientes anteriores puede controlar mejor el torque de los dientes maxilares anteriores para cerrar el espacio en ortodoncia lingual. Además, la distribución del estrés de la raíz del diente y del ligamento periodontal es pareja, lo que dificulta dañar el ligamento periodontal o provocar una resorción externa de la raíz del diente.