Background Interleukin-6 (IL-6) has been reported to be critical in oral squamous cell carcinoma (OSCC). However, the set of pathways that IL-6 might activate in OSCC are not fully understood. Methods IL-6 and Sox4 expressions were first determined with RT-qPCR, ELISA, Western blot, or immunohistochemistry in OSCC tissues, and correlations between IL-6 and Sox4 expression and patient pathological characteristics were examined, and Kaplan–Meier approach was employed for evaluating the prognostic utility in OSCC patients. CCK-8, EdU stain and colony formation assays were utilized to test cell proliferation in vitro. Mechanistically, downstream regulatory proteins of IL-6 were verified through chromatin immunoprecipitation, luciferase reporter, pull-down, and the rescued experiments. Western blot was used for detecting protein expression. A nude mouse tumorigenicity assay was used to confirm the role of IL-6 and Sox4 in vivo. Results IL-6 was upregulated in OSCC tissues, and Sox4 expression was positively correlated with IL-6 expression. High IL-6 and Sox4 expression was closely related to tumor size, TNM stage, and a poorer overall survival. Besides, IL-6 could accelerate OSCC cell proliferation by activating inflammasome via JAK2/STAT3/Sox4/NLRP3 pathways in vitro and in vivo. Furthermore, STAT3 played as a transcription factor which positively regulated Sox4, and IL-6 promotes Sox4 expression by activating JAK2/STAT3 pathway. Moreover, through the rescue experiments, we further confirmed that IL-6 could promote proliferation and NLRP3 inflammasome activation via JAK2/STAT3/Sox4 pathway in OSCC cells. Finally, knockdown of Sox4 suppressed OSCC growth in vivo, and antagonized the acceleration of IL-6 on tumor growth. Conclusions We confirmed that IL-6 plays an oncogenic role in OSCC progression by activating JAK2/STAT3/Sox4/NLRP3 pathway, which might be the therapeutic targets for OSCC remedy.
The purpose of this study was to assess the clinical oral status and investigate the effect of highly active antiretroviral therapy (HAART) on oral flora diversity in human immunodeficiency virus (HIV)-infected/acquired immune deficiency syndrome (AIDS) patients. We first recorded and analyzed the demographic indicators of 108 HIV-infected patients and assessed their periodontal health, dental health and oral lesion status by oral examination. Besides, we compared the changes in salivary microbial communities of healthy controls, before and after treatment of HAART-processed AIDS patients by Roche 454 sequencing and RT-qPCR. In HIV-infected/AIDS patients, age, sex, marital status, income level, smoking and oral health behaviors had an effect on periodontal clinical indicators; age and marital status were correlated with dental clinical indicators; most of them were accompanied by oral manifestations, mainly including candidiasis albicans, salivary gland disease, AIDS-associated periodontitis, and oral ulcers. Besides, a total of 487 species were detected in the saliva of AIDS patients. The microbial communities of HAART-unprocessed AIDS patients significantly differed from those processed patients, with 112 unique microbial species. More importantly, a large number of conditioned pathogens were also detected in the saliva samples of AIDS patients, which may be associated with opportunistic infections. Therefore, HAART might have a crucial role in salivary microecological balance in AIDS patients. And these patients should pay attention to the maintenance of oral health, and the early initiation of HAART may be important for the development of oral lesions.
Objectives: To investigate the genetic causes and characteristics of teeth of dentin dysplasia Shields Type-II(DD-II) in three Chinese families.Materials and Methods: Three Chinese families affected with DD-II were collected. The whole-exome sequencing(WES) and whole-genome sequencing(WGS) were conducted to screen for variations, and sanger sequencing was used to verify mutation sites. The physical and chemical characteristics of the affected teeth including tooth structure, hardness, mineral content and ultrastructure were investigated.Results: A novel frameshift deletion mutation c.1871_1874del(p.Ser624fs) in DSPP was found in family A and family B, while no pathogenic mutation was found in family C. The affected teeth's pulp cavities were obliterated, and the root canals were smaller than normal teeth and irregularly distributed comprising a network. The patients' teeth also had reduced dentin hardness and highly irregular dentinal tubules. The Mg content of the teeth was signi cantly higher than the controls but the Na content was obviously lower than the controls.Conclusions: A novel frameshift deletion mutation c.1871_1874del(p.Ser624fs) in the DPP region of the DSPP gene caused DD-II. The DD-II teeth demonstrated compromised mechanical properties and changed ultrastructure, suggesting an impaired function of DPP. Our ndings expanded the mutational spectrum of DSPP gene and strengthen the understanding of clinical phenotypes related to the frameshift deletion in the DPP region of the DSPP gene.Clinical Relevance: DSPP mutation can cause the characteristics of the affected teeth including tooth structure, hardness, mineral content and ultrastructure.
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