Hypomethylation-associated Sox11 upregulation promotes oncogenesis via the PI3K/AKT pathway in OLP-associated OSCC.

Oral lichen planus (OLP) is a particularly prevalent oral disorder with the potential to progress to oral squamous cell carcinoma (OSCC). SRY-box transcription factor 11 (Sox11) has been reported to serve as a prognostic marker for various cancers. However, the role and mechanism of Sox11 in OLP-related OSCC are unknown. Our results indicated that Sox11 was highly expressed, and that Sox11 promoter methylation was significantly reduced in OLP-associated OSCC tissues. High Sox11 expression and Sox11 promoter hypomethylation indicate a poor patient prognosis. According to in vivo and in vitro experiments, the knockdown of Sox11 inhibited proliferation, invasion, and migration while driving its apoptotic death in OSSC cells; Sox11 overexpression exerted the opposite effect as Sox11 knockdown. Mechanistically, knockdown of Sox11 inhibited PI3K/AKT and glycolysis pathway, and overexpression of Sox11 enhanced the PI3K/AKT and glycolysis pathways in OSCC cells. In addition, we demonstrated that Sox11 overexpression accelerated the progression of OSCC, at least in part by promoting PI3K/AKT pathway activation. In conclusion, our data indicated that the DNA hypomethylation-associated upregulation of Sox11 could promote oncogenic transformation via the PI3K/AKT pathway in OLP-associated OSCC. Therefore, Sox11 might be a reliable biomarker for predicting the progression of precancerous oral tissues.

Immune indices and oral health in patients infected with the human immunodeficiency virus.

BACKGROUND: The human immunodeficiency virus (HIV) is the causative agent of acquired immunodeficiency syndrome (AIDS). During the incubation period of AIDS, oral manifestations may precede systemic symptoms; therefore, it is vitally important to explore the relationship between HIV and oral health and other indicators. This study aimed to further assess the correlation between demographic risk factors, the dental health of HIV-infected patients, and the correlation of oral health indicators with CD4+ T-cell counts (CTCCs) and HIV viral loads (HIV-VLs). METHODS: Demographic data on 108 HIV-infected patients were first recorded by questionnaire from March 2016 to November 2018. Patients' dental health and oral lesions were assessed by a dental specialist; in addition, they were tested for CTCCs and HIV-VLs by flow cytometry and NucliSENS EasyQ® HIV-1 virometer. Finally, the links between CTCC, HIV-VL, and the dental health (including oral lesions) of the patients were analyzed. RESULTS: We found that age, marital status, and body mass index (BMI) were relevant to the patient's dental health (P < 0.05) and that their oral hygiene was relevant to their dental health (P < 0.05). However, HIV-VL was not directly related to periodontal/dental clinical indicators (P > 0.05). We discovered that the oral lesions in HIV-infected patients were related to decreased CTCCs and increased HIV-VLs (P < 0.05). CONCLUSIONS: We concluded that HIV-infected patients with severely impaired immune function tend to have poor dental health. Moreover, the prevalence of oral lesions was negatively correlated with CTCC and positively correlated with HIV-VL.

Identification of DSPP novel variants and phenotype analysis in dentinogenesis dysplasia Shields type II patients.

OBJECTIVES: To investigate the genetic causes and teeth characteristics of dentin dysplasia Shields type II(DD-II) in three Chinese families. MATERIALS AND METHODS: Data from three Chinese families affected with DD-II were collected. 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 families A and 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 significantly lower than that of the controls, but the Na content was obviously higher than that of the controls. CONCLUSIONS: A novel frameshift deletion mutation, c.1871_1874del (p.Ser624fs), in the DPP region of the DSPP gene causes DD-II. The DD-II teeth demonstrated compromised mechanical properties and changed ultrastructure, suggesting an impaired function of DPP. Our findings expand the mutational spectrum of the DSPP gene and strengthen the understanding of clinical phenotypes related to the frameshift deletion in the DPP region of the DSPP gene. CLINICAL RELEVANCE: A DSPP mutation can alter the characteristics of the affected teeth, including tooth structure, hardness, mineral content, and ultrastructure.

Clinical Oral Condition Analysis and the Influence of Highly Active Antiretroviral Therapy on Human Salivary Microbial Community Diversity in HIV-Infected/AIDS Patients.

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.

Interleukin-6 mediated inflammasome activation promotes oral squamous cell carcinoma progression via JAK2/STAT3/Sox4/NLRP3 signaling pathway.

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.

Effect of ruptured cavitated bubble cluster on the extent of the cell deformation by ultrasound.

In this paper, the bubble-cell model is presented. The effects of the spacing between the bubble population and the cell, the radius of the bubble and the bubble medium on the degree of cell deformation were investigated by solving the Helmholtz equation and the equilibrium of motion equation using COMSOL Multiphysis@ software. The ultrasonic transducer is applied in a round bottom flask with the bubble-cell model on the side of the ultrasonic transducer. When the distance between the bubble cluster and the cell gradually increases, the extent of deformation of the cell is reflected as first increasing and then decreasing, reaching the maximum deformation at D = 2. When the radius of the bubble is changed, there is a "constant frequency" at low frequency ultrasound in any distance case, at which the cell deformation will be violent. However, when the bubble medium is changed, there is no significant change in the degree of deformation of the cells. In other words, changes in the structure of the bubble-cell model affect the degree of cell deformation, but without structural changes, the degree of cell deformation changes very little.

Physical field simulation of the ultrasonic radiation method: An investigation of the vessel, probe position and power.

In this paper, the effects of ultrasonic probe position, vessel shape, and ultrasonic input power on the sound pressure distribution in the reactor were investigated by solving the Helmholtz equation using COMSOL Multiphysis@ software. Three different types of glass containers were used in the study, which are beaker, Erlenmeyer flask, and round bottom flask. The maximum value of sound pressure in the three containers will gradually increase when the distance between the probe and the bottom of the container decreases. When the distance decreases, the area of the high acoustic pressure region in the round bottom flask does not change significantly, while the area of the high acoustic pressure region in the beaker and Erlenmeyer flask increases sharply, which means that the use of the round bottom flask can reduce the influence of the dead zone on the preparation of nanomaterials. In addition, the change in power increases the value of the peak negative acoustic pressure in the vessel, enhancing the response efficiency of ultrasonic cavitation.

The effect of aging on sequestration and bioaccessibility of oxytetracycline in soils.

Veterinary antibiotics introduced into soil environment may change the composition and functioning of soil microbial communities and promote the spreading of antibiotic resistance. Actual risks depend on the antibiotic's bioaccessibility and sequestration in soils, which may vary with contact time and soil properties. We elucidated changes in the horsebean plant's bioaccessible oxytetracycline with increasing contact time in three different soils (cinnamon, red, and brown soil) and observed discrepancy in oxytetracycline dissipation using sequential extractions with H2O-, 0.01 M CaCl2-, and Mcllvaine- in the same three soils. The results showed lower quantities of oxytetracycline with increasing contact time over 20 days than the level in freshly contaminated soils but hugely discrepant quantities among the three tested soils. In addition, aging largely reduced dissipation of H2O-, 0.01 M CaCl2-, and Mcllvaine- extracted oxytetracycline in soils before planting. However, bioturbation helped increase the H2O-, CaCl2-, and Mcllvaine- extracted oxytetracyline from cinnamon and brown soils with aging. Lastly, correlation analysis indicated that bioaccessibility of oxytetracycline significantly correlates with the total of H2O-, CaCl2-, and Mcllvaine- extracted oxytetracycline (0.676**, p < 0.01) in soils, especially the H2O- (0.789**, p < 0.01) and Mcllvaine- (0.686**, p < 0.01) extracted oxytetracycline with aging. Overall, this study provides some basic understanding of the aging effect on sequestration and bioaccessibility of veterinary antibiotics in soils.

Evolution of the geometrical and electronic structures of Gan(n=2-26) clusters: a density-functional theory study.

Density-functional theory with generalized gradient approximation for the exchange-correlation potential has been used to calculate the lowest-energy geometries and electronic structure of neutral gallium clusters containing up to 26 atoms. Harmonic vibrational frequency analysis is undertaken to assure that the lowest-energy geometries are real local minima. With increasing cluster size, we find that the gallium clusters tend to adopt compact structures. The structures comprise triangular units that connect each other with different dihedral angles. The lowest-energy structure can be obtained by capping an atom on the structure of smaller one. The capping site occurs at a site where interactions with more atoms are available. The binding energy evolves monotonically with size, but Ga(8), Ga(14), and Ga(20) exhibit particularly higher stability. Except Ga(2) and Ga(4), all even-numbered gallium clusters we studied are closed-shell singlet states with a substantial highest occupied and lowest unoccupied molecular orbitals gap. The odd-numbered clusters are open shell with a small gap. The size dependence of cluster's ionization potentials and electron affinities is discussed and compared with available experiment.