Topical tacrolimus with different frequency for exfoliative cheilitis: a pilot study.

BACKGROUND: Tacrolimus is a new type immunosuppressant. The aim of this study was to evaluate the effectiveness of topical tacrolimus 0.1% ointment at 2 different frequencies in treating patients with exfoliative cheilitis. METHODS: A total of 40 patients with exfoliative cheilitis were randomly divided into the QD group receiving topical tacrolimus 0.1% ointment once a day or the QOD group receiving topical tacrolimus 0.1% ointment once-two-day. Patients were also applied wet dressing of saline twice a day. The effectiveness of treatment was defined as the percentage of improvement in signs or symptoms. RESULTS: 37 patients completed the 2-week treatment. And, a full set was analyzed. The effectiveness of topical tacrolimus 0.1% ointment for relief in objective sign and subjective symptom was 50% and 67.5%% in the QD group, respectively. For the QOD group, the effectiveness of sign and symptom relief was 50% and 73.5%. There was no significant difference of effectiveness between application topical tacrolimus once a day and once 2 days. CONCLUSION: Our data suggested that application of topical tacrolimus 0.1% ointment once a day and once 2 days had similar clinical effectiveness for sign and symptom relief in patients with exfoliative cheilitis.

Loss of TACC1 variant25 inducing cell proliferation and suppressing autophagy in head and neck squamous carcinoma.

Transforming acidic coiled-coil containing protein1 (TACC1) is closely related to transcription, translation and centrosome dynamics. Dysregulation of TACC1 is associated with multiple malignancies. Alternative splicing (AS) of TACC1 produces multiple variants, which are of great significance in cancer biology. However, the expression and biological functions of TACC1 variants in head and neck squamous cell carcinoma (HNSCC) remain unclear. In this study, we found for the first time that TACC1 variants exhibited a characteristic expression pattern and that TACC1 variant25 (TACC1v25) was downregulated in HNSCC tissues and cell lines. Overexpression of TACC1v25 in Cal27 and Fadu cells significantly inhibited proliferation and promoted autophagy. Moreover, expression levels of nuclear pERK and p-mTOR were significantly decreased, while the expression of Beclin-1 and the LC3II/LC3I ratio were increased in TACC1v25-overexpressed Cal27 and Fadu cells. After the addition of AKT activator SC79 to TACC1v25-overexpressed Cal27 and Fadu cells, the autophagy levels were remarkably rescued. In conclusion, TACC1v25 inhibits HNSCC progression through the ERK and AKT/mTOR pathways by inhibiting proliferation and increasing autophagy. TACC1v25 might have potential use as a tumour suppressor in HNSCC.

A model for comprehensive oral biological age score with oral and systemic clinical parameters.

BACKGROUND: Biological age reflects the functional status of an individual. The purpose of the study was to develop a model for estimating oral biological age with oral and systemic parameters. METHODS: A total of 248 subjects who had a routine health check were assessed with oral and general clinical examination. Chi-square test was performed to screen oral clinical candidate indicators. General parameters were analyzed by Pearson correlation coefficient and principal component analysis to develop a general biological age score. A final comprehensive model of oral biological age score was established by combining oral and general biological age score. RESULTS: A total of eight oral indicators (mucosal blood blister, mucosal dryness, impacted tooth, missing teeth, residual crowns, dental calculus, gingival hyperemia, and gingival recession) and 10 general clinical indicators (triglyceride, creatinine, blood urea nitrogen, glucose, total cholesterol, mean erythrocyte hemoglobin concentration, mean erythrocyte hemoglobin, uric acid, body weight, and systolic blood pressure) were selected for oral and general biological age score, respectively (r > 0.25, P < 0.05). A model of comprehensive oral biological age score was then formed by principal component analysis: 0.046 triglyceride + 0.010 creatinine + 0.141 blood urea nitrogen + 0.048 glucose + 0.068 total cholesterol + 0.014 mean erythrocyte hemoglobin concentration + 0.082 mean erythrocyte hemoglobin + 0.001 uric acid + 0.020 body weight + 0.005 systolic blood pressure + 0.037 oral biological age score -10.908. The score was increased accordingly with CA. CONCLUSION: Oral biological age can be easily estimated clinically by the model of comprehensive oral biological age score using oral and systemic clinical parameters by general practitioners.

Effect of Suo Quan Wan on the bladder function of aging rats based on the ß-adrenoceptor.

Suo Quan Wan (SQW) has been used to treat lower urinary tract symptoms (LUTS) in elderly patients for hundreds of years in China. ß-adrenoceptors (ß-ARs), particularly ß3-adrenoceptor (ß3-AR), was reported to be important in the bladder dysfunction of the elderly. The present study was conducted to explore the effect of ß-AR, and particularly the ß3-adrenoceptor, in aging rat bladder function in vitro and to test the therapeutic effect of SQW on LUTS in an aging rat model based on the ß3-adrenoceptor. Briefly, the bladder detrusor muscles of young (age, 3 months) and aging (age, 15 months) female rats were separated. A ß-AR non-selective agonist, isoprenaline (ISO), subtype ß3-AR agonist (BRL37344A) and ß3-AR antagonist (SR59230A) were used to define the tension change of detrusor muscles between young and aging rats in vitro. For blank controls, 12 young rats were marked, and 48 aging female rats were randomly divided into four groups as follows: Model, SQW high, SQW middle and SQW low. Following oral administration of SQW for 6 weeks in aging rats, urodynamic and bladder detrusor tests were used to evaluate the therapeutic effect of SQW. The expression of ß3-AR mRNA was investigated using reverse transcription-quantitative polymerase chain reaction. Using ISO and BRL37344A in vitro, maximum relaxation (Emax), intrinsic activity (IA), and log (50% effective concentration) (PD2) were significantly decreased in aging rats compared with that in young rats (P<0.05). Significant changes were also observed in the ß3-AR antagonist experiment, which blocked ISO-induced relaxation, with significant decreases observed in Emax, IA and PD2, and a significant increase observed in PA2 for the aging rats compared with the young controls (P<0.05). SQW was demonstrated to enhance bladder control, storage and contraction ability. Furthermore, SQW was able to increase the sensitivity and expression of ß3-AR in an aging rat. In conclusion, the decrease in ß3-AR sensitivity in aging rats and the expression resulted in bladder detrusor dysfunction. In addition, the therapeutic effect of SQW against LUTS relies on the former's effect on the urethral sphincter, bladder detrusor and ß3-AR.

Absence of high-risk HPV 16 and 18 in Chinese patients with oral squamous cell carcinoma and oral potentially malignant disorders.

BACKGROUND: The critical role of human papillomavirus (HPV) in cancer has been recognized, but the involvement of HPV in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) is still controversial. The aim of this study was to identify and verify the prevalence of high-risk HPV infection (HPV16 and 18) in Chinese patients with OSCC or OPMD using real-time PCR and DNA sequencing. METHODS: Paired tissue and serum DNA samples were extracted from 40 Chinese patients with OSCC and 59 with OPMD. A SYBR Green-based real-time PCR assay was developed to detect the E6 gene of HPV16 and HPV18. Suspicious positive samples were then sequenced to eliminate false positives. RESULTS: We found that none of the tissue and serum samples of OSCCs and OPMDs were positive for HPV16 E6 or 18 E6, using both real-time PCR and DNA sequencing. Overall, 3 of 198 (1.52 %) and 7 of 198 (3.54 %) samples were false-positive for HPV16 E6 and HPV18 E6, respectively, using real-time PCR. CONCLUSION: The lack of HPV16 and HPV18 detected in this study indicates that high-risk HPV 16 and 18 infections are uncommon in Chinese patients with OSCC and OPMD. Real-time PCR followed by DNA sequencing for HPV DNA detection is an effective strategy to rule out false positives.

[Effect of Zhuangyao Jianshen Wan (ZYJCW) on P2X1 and P2X3 mRNA expressions in rats with diuresis caused by kidney deficiency].

To investigate the urination-reducing effect and mechanism of Zhuangyao Jianshen Wan (ZYJCW). In this study, SI rats were subcutaneously injected with 150 mg · kg(-1) dose of D-galactose to prepare the sub-acute aging model and randomly divided into the model group, the Suoquan Wan group (1.17 g · kg(-1) · d(-1)), and ZYJCW high, medium and low dose groups (2.39, 1.20, 0.60 g · kg(-1) · d(-1)) , with normal rats in the blank group. They were continuously administered with drugs for eight weeks. The metabolic cage method was adopted to measure the 24 h urine volume and 5 h water load urine volume in rats. The automatic biochemistry analyzer was adopted to detect urine concentrations of Na+, Cl-, K+. The ELISA method was used to determine serum aldosterone (ALD) and antidiuretic hormone (ADH). The changes in P2X1 and P2X3 mRNA expressions in bladder tissues of rats were detected by RT-PCR. According to the results, both ZYJCW high and medium dose groups showed significant down-regulations in 24 h urine volume and 5 h water load urine volume in (P <0.05, P <0.01), declines in Na+ and Cl- concentrations in urine (P <0.01), notable rises in plasma ALD and ADH contents (P <0.05, P <0.01) and remarkable down-regulations in the P2X1 and P2X3 mRNA expressions in bladder tissues (P <0.01). The ZYJCW low dose group revealed obvious reductions in Na+ and Cl- concentrations in urine (P <0.01). The results indicated that ZYJCW may show the urination-reducing effect by down-regulating the P2X1 and P2X3 mRNA expressions in bladder tissues of rats with diuresis caused by kidney deficiency.

Decreased expression of GRIM-19 by DNA hypermethylation promotes aerobic glycolysis and cell proliferation in head and neck squamous cell carcinoma.

To identify novel tumor suppressor genes that are down-regulated by promoter hypermethylation in head and neck squamous cell carcinoma (HNSCC), genome-wide methylation profiling was performed using a methylated DNA immunoprecipitation (MeDIP) array in HNSCC and normal mucosa tissue samples. Promoter hypermethylation of the candidate gene, gene associated with retinoid-interferon induced mortality-19 (GRIM-19), was confirmed in HNSCC cell lines. Multivariate regression analysis determined that GRIM-19 hypermethylation was an independent significant factor for HNSCC diagnosis (OR:125.562; P < 0.001). HNSCC patients with lower ratio of GRIM-19/ACTB hypermethylation had increased overall and disease free survival. Furthermore, the optimal cutoff provided 90% sensitivity and 77% specificity of GRIM-19 hypermethylation as a diagnostic marker for HNSCC. Ectopic expression of GRIM-19 in HNSCC cells led to increased oxygen consumption, reduced glycolysis and decreased cell proliferation. HNSCC cells ectopically expressing GRIM-19 displayed increased p53 activity as well as decreased Stat3 and HIF-1α activities. Moreover, GRIM-19 knockdown not only resulted in decreased oxygen consumption and increased aerobic glycolysis but also promoted cell proliferation and tumorigenic capacity in HNSCC cells. Our data indicate that decreased GRIM-19 expression due to promoter hypermethylation may be important in head and neck carcinogenesis by promoting cell proliferation and regulating metabolic activity.

Notch1 mutations are drivers of oral tumorigenesis.

Disruption of NOTCH1 signaling was recently discovered in head and neck cancer. This study aims to evaluate NOTCH1 alterations in the progression of oral squamous cell carcinoma (OSCC) and compare the occurrence of these mutations in Chinese and Caucasian populations. We used a high-throughput PCR-based enrichment technology and next-generation sequencing (NGS) to sequence NOTCH1 in 144 samples collected in China. Forty-nine samples were normal oral mucosa from patients undergoing oral surgery, 45 were oral leukoplakia biopsies, and 50 were chemoradiation-naïve OSCC samples with 22 paired-normal tissues from the adjacent unaffected areas. NOTCH1 mutations were found in 54% of primary OSCC and 60% of premalignant lesions. Importantly, almost 60% of patients with leukoplakia with mutated NOTCH1 carried mutations that were also identified in OSCC, indicating an important role of these clonal events in the progression of early neoplasms. We then compared all known NOTCH1 mutations identified in Chinese patients with OSCC with those reported in Caucasians to date. Although we found obvious overlaps in critical regulatory NOTCH1 domains alterations and identified specific mutations shared by both groups, possible gain-of-function mutations were predominantly seen in Chinese population. Our findings demonstrate that premalignant lesions display NOTCH1 mutations at an early stage and are thus bona fide drivers of OSCC progression. Moreover, our results reveal that NOTCH1 promotes distinct tumorigenic mechanisms in patients from different ethnical populations.

MicroRNA-155 in oral squamous cell carcinoma: Overexpression, localization, and prognostic potential.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a common malignancy with poor prognosis. MicroRNAs (miRNAs) play an important role in cancer, but their role in OSCC is not clarified. METHODS: We performed miRNA microarray, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and fluorescence in situ hybridization (FISH) to examine miRNA expression in OSCC and paired adjacent cancer-free mucosal (ACF) tissues. RESULTS: Thirteen miRNAs, including miRNA-155, were upregulated (>2-fold) in OSCC against ACF. MiRNA-155 was confirmed to have significantly higher expression in OSCC against ACF (paired-samples t test; p = .041) and it was localized in the cancer nest, inflammatory area, and vascular endothelium of OSCC. High expression of miRNA-155 in ACF tissue was an independent prognostic indicator for OSCC survival. CONCLUSION: MiRNA-155 was overexpressed in OSCC and it was located in the cancer nest, inflammatory area, and vascular endothelium of OSCC. High miRNA-155 expression level in ACF may predict poor prognosis in patients with OSCC.

Gastroprotective effect and mechanism of patchouli alcohol against ethanol, indomethacin and stress-induced ulcer in rats.

Pogostemonis Herba is an important Chinese medicine widely used in the treatment of gastrointestinal dysfunction. Patchouli alcohol (PA), a tricyclic sesquiterpene, is the major active constituent of Pogostemonis Herba. This study aimed to investigate the possible anti-ulcerogenic potential of PA and the underlying mechanism against ethanol, indomethacin and water immersion restraint-induced gastric ulcers in rats. Gross and histological gastric lesions, biochemical and immunological parameters were taken into consideration. The gastric mucus content and the antisecretory activity were analyzed through pylorus ligature model in rats. Results indicated that oral administration with PA significantly reduced the ulcer areas induced by ethanol, indomethacin and water immersion restraint. PA pretreatment significantly promoted gastric prostaglandin E2 (PGE2) and non-protein sulfhydryl group (NP-SH) levels, upregulated the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) mRNA expression, and considerably boosted the gastric blood flow (GBF) and gastric mucus production in comparison with vehicle. In addition, PA modulated the levels of interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α). The levels of glutathione (GSH), catalase (CAT) and malonaldehyde (MDA) were also restored by PA. However, the gastric secretion parameters (pH, volume of gastric juice and pepsin) did not show any significant alteration. These findings suggest that PA exhibited significant gastroprotective effects against gastric ulceration. The underlying mechanisms might involve the stimulation of COX-mediated PGE2, improvement of antioxidant and anti-inflammatory status, preservation of GBF and NP-SH, as well as boost of gastric mucus production.