Effect of ALA-PDT on inhibition of oral precancerous cell growth and its related mechanisms.

BACKROUND: Early treatment of oral precancerous lesions is considered as a key strategy for in oral carcinogenesis prevention. Increasing evidence has suggested that the transforming growth factor beta (TGF-ß) signaling pathway is tightly involved in the process of oral-carcinogenesis. In this study, we investigated the inhibition effect and potential mechanism of 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) in human oral precancerous cells via TGF-ß pathway. MATERIALS AND METHODS: Here, the dysplastic oral keratinocyte (DOK) cells were incubated with ALA concentration of 1 mM/mL for 4 h and then irradiated with a Helium-Neon (He-Ne) ion laser at 633 nm (200 mW/cm2). The control cells were cultured in Dulbecco's modified Eagle's medium (DMEM) medium. We analyzed the differentially expressed genes and correlated pathways in oral precancerous cells following ALA-PDT using Affymetrix microarrays. TGF-ß pathway was analyzed by quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting. Bioinformatics analysis was performed to evaluate the expression of TGF-ß1 in human oral cancer samples and adjacent normal samples. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), flow cytometry, 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and wound healing assay were used to assess the effects of ALA-PDT plus TGF-ß receptor inhibitor (LY2109761) in DOK cells. RESULTS: The TGF-ß signaling could exert in suppressive effects on DOK cells after ALA-PDT. The cell proliferation and migration rate of DOK cells was significantly reduced and apoptosis and ROS generation induced more effectively by ALA-PDT combined with LY2109761. Furthermore, cell cycle analysis revealed that the combined treatment resulted in G0/G1 phase arrest. CONCLUSIONS: ALA-PDT suppresses the growth of oral precancerous cells by regulating the TGF-ß signaling pathway, and its suppressive effect was enhanced using LY2109761. These results indicate that it could be a promising alternative treatment against oral precancerous lesions.

[Determination of human papillomavirus in oral leukoplakia,oral lichen planus and oral squamous cell carcinoma].

OBJECTIVE: To investigate the possibility for human papillomavirus (HPV) infection to be a predictable signal for the carcinogenesis of oral mucosa by comparing the prevalences of HPV in each stage of oral mucosal carcinogenesis and to compare the sensitivity differences of the two methods in detecting HPV infection in oral cavity. METHODS: The hybrid capture (HC-II) was used to detect infection of HPV in 255 samples taken from 12 cases of healthy oral mucosa, 211 cases of patients with pathological diagnosis and 32 cases of patients with clinical diagnosis. The diagnosed cases included 8 cases of benign lesions of the oral mucosa, precancerous lesions [74 cases of oral leukoplakia (OLK) with hyperplasia and 42 cases of OLK with oral epithelial dysplasia (OED)], 91 cases of precancerous condition [oral lichen planus (OLP)] and 28 cases of oral squamous cell carcinoma (OSCC). And in situ hybridization (ISH) was used to detect infection of HPV in 33 cases of OSCC and 76 cases of OLK, including 30 cases of hyperplasia, 15 cases of mild OED, 15 cases of moderate OED and 16 cases of severe OED. RESULTS: The prevalence of HPV in OLP samples was higher (12.12%, 8/66) than that of OLK (2.59%, 3/116) (χ(2)=4.666, P=0.031) and OSCC(7.14%, 2/28, χ(2)=0.513, P=0.474). The prevalence of HPV in OSCC (7.14%, 2/28) was higher than that of OLK (2.59%, 3/116), and no significant difference was found. There was only one case of smoke spot and statistical analysis was not carried out. ISH was used to detect type 16/18 and type 31/33 HPV DNA in 109 cases of oral mucosal lesions in paraffin sections and only one case of OSCC was HPV positive. Thirty-seven cases were detected by HC-II and ISH methods at the same time. The same negative results by the two methods were found in 94.6% samples (35/37). In the other two samples, one was OSCC with early infiltration and the other was OLK with hyperplasia, The HC-II results were positive while the ISH results were negative. The patients with OLP and HPV testing results were followed up and the average follow-up period was (36.2 ± 10.5) months. It was found that three of them had a malignant transformation, and the malignant transformation rate of HPV positive patients was 12.50% (1/8), which was higher than that of HPV negative patients (3.45%, 2/58), and the difference was not statistically significant, P=0.249. CONCLUSION: HC-II assay was more sensitive in detecting HPV infection of oral mucosal lesions than ISH. The results of this study showed that there was insufficient evidence for taking HPV infection as a predictor of OLK carcinogenesis. Patients suffering from OLP were in a precancerous condition. The prevalence of HPV in OLP patients of this study was higher than that in OLK and OSCC patients, suggesting that for some reason, OLP patients were susceptible to HPV. HPV testing can be considered as routine in patients with OLP, and HC-II assay was recommended. And patients with OLP and HPV positive should be followed up regularly.

[Correlation between the quantity of oral mucosal micronucleus cells and cancerization].

OBJECTIVE: To explore the relationship between micronuclei and malignant development of oral epithelial dysplasia (OED). METHODS: Oral exfoliated cells were smeared from 30 control subjects, 46 patients with oral lichen planus (OLP), 78 patients with oral leukoplakia (OLK) and hyperplasia, 30 patients with OLK and mild OED, 29 patients with OLK and moderate OED, 15 patients with OLK and severe OED and 22 patients with oral squamous cell carcinoma (OSCC). RESULTS: Micronucleus rates declined according to the order of OSCC, OLK and severe OED, OLK and moderate OED, OLK and mild OED, OLK and hyperplasia, OLP and control groups (P<0.001). CONCLUSION: Micronuclei may reflect the progression of oral epithelial malignant changes. It could be used in monitoring cancerization in following up cases regularly.

[Levels of interlukin-6 and tumor necrosis factor-α in saliva of patients with type 2 diabetes mellitus and oral lichen planus].

OBJECTIVE: To study the relationship between type 2 diabetes mellitus (T2DM) and oral lichen planus (OLP) by detecting the level of salivary tumor necrosis factor (TNF-α) and interlukin-6 (IL-6). METHODS: Subjects were divided into 4 groups: T2DM/OLP group 29 patients, T2DM group 39 patients, OLP group 21 patients, and control group 43 individuals. The salivary interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) were detected by enzyme-linked immuno sorbent assay (ELISA). RESULTS: (1) The level of salivary IL-6 in patients with T2DM/OLP [(12.30 ± 16.03) ng/L] was significantly higher than those in T2DM [(6.29 ± 5.91) ng/L] and OLP groups [(3.64 ± 4.47) ng/L], P<0.05. The level of salivary IL-6 was significantly lower in OLP group [(3.64 ± 4.47) ng/L] than in control group [(7.91 ± 4.05) ng/L], P<0.001. The level of salivary TNF-α in T2DM group [(8.80 ± 8.41) ng/L] was significantly lower than those in OLP [(14.02 ± 9.65) ng/L] and control groups [(15.02 ± 6.13) ng/L], P<0.05. (2) The level of salivary TNF-α is significantly negative correlated with pH value of saliva in T2DM/OLP group(r=-0.593, P<0.01);The level of salivary TNF-α and IL-6 are significantly positive correlated with waistline in control group(r=0.312,P=0.05).(3) The levels of salivary IL-6 and TNF-α were positively related to OLP clinical type, P<0.05. (4)When OLP played an overlying role on T2DM, the level of TNF-α was weakened and that of IL-6 was strengthened. CONCLUSION: When T2DM and OLP are in concurrence,there is a synergistic effect,and the secretion of IL-6 increases markedly; The level of salivary TNF-α is associated with local oral environment.

Multifactor analysis of patients with oral sensory complaints in a case-control study.

BACKGROUND: There are an increasing number of patients with oral sensory complaints (OSCs) presenting to our dental clinic. For most dentists, it is difficult to distinguish burning mouth syndrome (BMS) from other oral mucosal diseases that may cause symptoms such as burning mouth. It is beneficial to effectively distinguish OSC patients to reduce misdiagnosis and eliminate burning symptoms as much as possible. METHODS: Patients with oral burning sensations in the oral mucosal disease clinic were collected from the Peking University Hospital of Stomatology between September 1, 2014 and December 31, 2018. After excluding oral candidiasis, anemic stomatitis, dental material allergy, and other diseases from patients with oral sensory complaints, basic conditions such as gender, age, education level, job status, hyperglycemia, hypertension, hyperlipidemia, history of brain abnormalities, history of cervical spondylitis, history of thyroid disease, history of thyroid disease and insomnia were obtained. The BMS patients were compared with the control group. The t test and Chi-square test were used for statistical analysis to compare the clinical symptoms of these diseases and explore the risk factors for BMS. RESULTS: In this case-control study, 395 patients (321 females and 74 males, mean age 55.26 ±â€Š10.51 years) with oral sensory complaints and 391 healthy controls (281 females and 110 males, mean age 47.11 ±â€Š13.10 years) were enrolled, among which, 8.4% (33/395) had oral candidiasis, 1.3% (5/395) had dental material allergy, 0.8% (3/395) had anemic stomatitis and 0.5% (2/395) had lichen planus. A total of 352 patients were eventually diagnosed with BMS. Anxiety and depression were more severe in BMS patients, as were the incidences of sleep disorders and brain abnormalities. Logistic regression analysis showed that age (odds ratio [OR] = 2.79, 95% confidence interval [CI]: 1.61-4.83, P < 0.001), total cholesterol level (OR = 2.92, 95% CI: 1.32-6.50, P = 0.009) and anxiety score (OR = 1.75, 95% CI: 1.01-2.77, P = 0.017) significantly increased the incidence of BMS. Patients with hyperglycemia (OR = 0.46, 95% CI: 0.23-0.89, P = 0.022), low body mass index (BMI: OR = 0.57, 95% CI: 0.34-0.93, P = 0.026) and low education level (OR = 3.43, 95% CI: 1.91-6.15, P < 0.001) were more likely to suffer from BMS. CONCLUSIONS: Oral candidiasis, anemic stomatitis, and dental material allergy with burning symptoms should be excluded from patients with BMS. It is recommended to conduct a questionnaire survey (including anxiety and depression), blood cell analysis, and salivary fungus culture for all patients with an oral burning sensation. It is necessary to conduct a patch test on patients with oral burning sensations and metal restorations.

Light-Driven Reversible Transformation between Self-Organized Simple Cubic Lattice and Helical Superstructure Enabled by a Molecular Switch Functionalized Nanocage.

Self-organized stimuli-responsive smart materials with adjustable attributes are highly desirable for a plethora of device applications. Simple cubic lattice is quite uncommon in soft condensed matter due to its lower packing factor. Achieving a stable simple cubic soft lattice and endowing such a lattice with dynamic reconstruction capability solely by a facile light irradiation are of paramount significance for both fundamental studies and engineering explorations. Herein, an elegant stable self-organized simple cubic soft lattice, i.e., blue phase II, in a chiral liquid crystal (LC) system is disclosed, which is stable down to room temperature and exhibits both reversible lattice deformation and transformation to a helical superstructure, i.e., cholesteric LC, by light stimulation. Such an amazing trait is attained by doping a judiciously designed achiral photoresponsive molecular switch functionalized polyhedral oligomeric silsesquioxane nanocage into a chiral LC host. An unprecedented reversible collapse and reconstruction of such a high symmetric simple cubic blue phase II driven by light has been achieved. Furthermore, a well-defined conglomerate micropattern composed of simple cubic soft lattice and helical superstructure, which is challenging to fabricate in organic and inorganic crystalline materials, is produced using photomasking technology. Moreover, the promising photonic application based on such a micropattern is demonstrated.

[The effect of oral candida to development of oral leukoplakia into cancer].

OBJECTIVE: To investigate the rate of candidal infection in different condition of oral epithelia, that may imply the possibility of candida in the canceration of oral leukoplakia. METHODS: Saliva culture was used to detect the infection of candida in 100 cases of healthy control group, 110 cases of oral leukoplakia and 11 cases of oral squamous cell carcinoma, whose smoking condition were collected carefully. The results were analyzed by Crosstabs, Bivariate Correlations and Binary Logistic Regression analysis. RESULTS: With Crosstabs and Bivariate Correlations analysis, there was significant correlation within malignant level of oral leukoplakias and candidal infection rates (r = 0.148, P = 0.032). With Crosstabs single factor analysis, there was significant correlation within saliva culture results and pathological types (chi(2) = 21.757, P = 0.010). With Binary Logistic Regression analysis, there was significant correlation within saliva culture results and both of subjects, ages (OR = 0.72, P = 0.000) and duration of smoking (OR = 0.37, P = 0.01). CONCLUSION: Candidal infection may be one of the most important factors inducing dysplasia of epithelia and malignant transformation of oral leukoplakia. So saliva culture should be taken as a rule for patients with oral leukoplakia. The follow-up of oral leukoplakia patients with candidal infection should be enhanced.

Peroxynitrite induces arteriolar smooth muscle cells membrane hyperpolarization with arteriolar hyporeactivity in rats.

Peroxynitrite (ONOO-) has been recently known to act as a potent cytotoxin during pathogenesis of various diseases. This study aimed to investigate the possible effect of ONOO- on the cremaster muscle arteriolar reactivity in response to noradrenaline and subsequently determined whether membrane hyperpolarization and potassium channel activation were involved in ONOO(-)-induced alteration of arteriolar reactivity. The results demonstrated that 1) ONOO- could decrease arteriolar reactivity in a time- and concentration-dependent manner with no significant alteration of arteriolar diameter; 2) Superfusion with 20 microM ONOO- over 40 minutes showed slight but not significant influence on the resting potential (Em) of arteriolar smooth muscle cells (ASMCs). However, ASMCs subjected to 50 or 100 microM ONOO- administration were significantly hyperpolarized. As control, treatment with 50 microM decomposed ONOO- or Kreb's solution had little effect on the Em of ASMCs; 3) ONOO(-)-induced arteriolar hyporeactivity could be greatly reversed by co-administration of KCl and partially by TEA. The above results indicated that membrane hyperpolarization and potassium channel activation were preferentially responsible for the reduction of cremaster muscle arteriolar reactivity after exposure to ONOO-.

Watermarking on 3D mesh based on spherical wavelet transform.

In this paper we propose a robust watermarking algorithm for 3D mesh. The algorithm is based on spherical wavelet transform. Our basic idea is to decompose the original mesh into a series of details at different scales by using spherical wavelet transform; the watermark is then embedded into the different levels of details. The embedding process includes: global sphere parameterization, spherical uniform sampling, spherical wavelet forward transform, embedding watermark, spherical wavelet inverse transform, and at last resampling the mesh watermarked to recover the topological connectivity of the original model. Experiments showed that our algorithm can improve the capacity of the watermark and the robustness of watermarking against attacks.

Effect of SOD and NaHCO3 on the vascular hyporeactivity of rats after severe hemorrhagic shock.

OBJECTIVE: To investigate the effect of SOD and NaHCO3 on the vascular hyporeactivity after severe hemorrhagic shock in rats. METHODS: Twenty eight Sprague-Dawley rats were divided randomly into 4 groups of 7 each: SOD-treated group, NaHCO3-treated group, SOD+NaHCO3-treated group and normal saline-treated control group. The responses of arterioles to norepinephrine (NE), the effects of dopamine on blood pressure, blood flow velocity in arterioles, the mean arterial pressure (MAP), and the survival time within 24 h were measured. RESULTS: Two hours after shock, the arteriolar vasoreactivity was significantly reduced and threshold concentration of NE was increased by 24 to 27 folds. After beting treated separately with SOD, NaHCO3 and SOD+NaHCO3, arteriolar vasoreactivity was restored to some extent, among which the SOD+NaHCO3 group obtained a most significant effect with decreased threshold concentration of NE to 21% of its normal level. In SOD+NaHCO3-treated group, injection of dopamine indicated a most significant effect on MAP with 1.9 times more than that in control group, and the enhanced MAP was maintained at a level of more than 13.33 kPa after reinfusion of shed blood. The blood flow in arteriole was 2.54-fold higher than that in control group after 2 h resuscitation. The average survival time in SOD+NaHCO3- treated group was 2.9 times longer than that in control group. CONCLUSIONS: SOD and NaHCO3 could both recover the lower vasoreactivity and increase the enhancing effect of dopamine on blood pressure of rats in severe hemorrhagic shock, suggesting that coadministration of SOD and NaHCO3 could be a new approach to the treatment of severe hemorrhagic shock.