Effects of melatonin receptor expression on prognosis and survival in oral squamous cell carcinoma patients.

Melatonin receptors can inhibit breast and prostate cancers; however, little is known regarding their effects on oral squamous cell carcinoma. In this study, we collected specimens from 81 patients with oral squamous cell carcinoma and analysed clinicopathological data retrospectively. In addition, the expression of the melatonin receptor was analysed immunohistochemically. Survival rates were calculated using the Kaplan-Meier method and log-rank test. Multivariate analysis was performed based on the Cox proportional-hazards model. Further, an in vitro study was performed using YD15 cells. The cells were transfected with siRNA targeting melatonin receptor 1A and 1B for evaluating the malignancy of melatonin receptors by western blotting, trypan blue-exclusion, colony-forming, wound-healing, and invasion assays. Survival decreased as melatonin receptor expression and clinical and pathological tumour-node-metastasis stages increased. A Cox proportional-hazard model showed that melatonin receptor 1A may serve as a significant predictor of the survival rate of patients with oral squamous cell carcinoma [hazard ratio = 1.423, 95% confidence interval (CI) = 1.019-1.988, p = 0.038]. Melatonin receptor 1A and 1B knockdown significantly suppressed proliferation, migration ability, and invasion ability of YD15 cells in vitro. Our findings reveal that inhibiting melatonin receptor expression may suppress oral squamous cell carcinoma development.

Clinical characteristics and differences of 802 acral tumours, categorized by anatomical sites.

BACKGROUND: Acral skin tumours are common, but information in the literature regarding their incidence is scarce. AIM: To investigate the clinical characteristics and differences in incidence of benign and malignant acral tumours by anatomical site. METHODS: A retrospective review was conducted of 802 patients with acral skin tumours confirmed by skin biopsy between January 2010 and December 2019. Age, sex, duration, symptoms and sites were obtained from medical records and photographs. RESULTS: The mean age of onset was 43.8 years, the male/female ratio was 1 : 1.41, and the mean duration was 68.8 months. Most tumours were asymptomatic (66.7%). In total, 802 acral tumours were identified: 512 (63.8%) were benign and 290 (36.2%) were malignant. The most common benign tumours were benign melanocytic lesions (n = 239), and the most common malignant tumours were melanoma (n = 234). The most common site was the sole (n = 408). Benign melanocytic lesions, melanoma and epidermal cysts were more frequent on the foot, whereas pyogenic granuloma, glomus tumours, haemangiomas and mucous cysts were more frequent on the hand. Glomus tumours, fibromas, mucous cysts and osteomas were more frequent on the nail portion, and benign melanocytic lesions and epidermal cysts were more frequent on the non-nail portion. CONCLUSION: This study reports the incidence of various benign and malignant acral tumours according to site, and we believe the results will be helpful in making a clinical diagnosis.

Expression of the glutamine metabolism-related proteins glutaminase 1 and glutamate dehydrogenase in canine mammary tumours.

Glutamine metabolism is an important metabolic pathway for cancer cell survival, and there is a critical connection between tumour growth and glutamine metabolism. Because of their similarities, canine mammary carcinomas are useful for studying human breast cancer. Accordingly, we investigated the correlations between the expression of glutamine metabolism-related proteins and the pathological features of canine mammary tumours. We performed immunohistochemical and western blot analysis of 39 mammary tumour tissues. In immunohistochemical analysis, the expression of glutaminase 1 (GLS1) in the epithelial region increased according to the histological grade (P < .005). In the stromal region, complex-type tumours displayed significantly higher GLS1 intensity than simple-type tumours. However, glutamate dehydrogenase expression did not show the same tendencies as GLS1. The western blot results were consistent with the immunohistochemical findings. These results suggest that the expression of GLS1 is correlates with clinicopathological factors in canine mammary tumours and shows a similar pattern to human breast cancer.

Human DBR1 modulates the recycling of snRNPs to affect alternative RNA splicing and contributes to the suppression of cancer development.

The contribution of RNA processing to tumorigenesis is understudied. Here, we report that the human RNA debranching enzyme (hDBR1), when inappropriately regulated, induces oncogenesis by causing RNA processing defects, for example, splicing defects. We found that wild-type p53 and hypoxia-inducible factor 1 co-regulate hDBR1 expression, and insufficient hDBR1 leads to a higher rate of exon skipping. Transcriptomic sequencing confirmed the effect of hDBR1 on RNA splicing, and metabolite profiling supported the observation that neoplasm is triggered by a decrease in hDBR1 expression both in vitro and in vivo. Most importantly, when modulating the expression of hDBR1, which was found to be generally low in malignant human tissues, higher expression of hDBR1 only affected exon-skipping activity in malignant cells. Together, our findings demonstrate previously unrecognized regulation and functions of hDBR1, with immediate clinical implications regarding the regulation of hDBR1 as an effective strategy for combating human cancer.

Staphylococcal enterotoxin IgE sensitization in late-onset severe eosinophilic asthma in the elderly.

BACKGROUND: Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late-onset asthma. Recent studies suggest staphylococcal enterotoxin IgE (SE-IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late-onset elderly asthma. OBJECTIVE: We aimed to examine the associations of SE-IgE sensitization with late-onset asthma in the elderly, using a database of elderly asthma cohort study. METHODS: A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE-IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12-month follow-up period. RESULTS: At baseline, serum SE-IgE concentrations were significantly higher in patients with asthma than in controls [median 0.16 (interquartile range 0.04-0.53) vs. 0.10 (0.01-0.19), P < 0.001]. Elderly asthma patients with high SE-IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE-IgE levels. In multivariate logistic regression analyses, the associations between serum SE-IgE concentrations and severe asthma were significant, independently of covariables [SE-IgE-high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86-30.03, P = 0.005]. Multiple correspondence analyses also showed that high serum SE-IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first report on the significant associations of SE-IgE sensitization with late-onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late-onset eosinophilic asthma in the elderly.

Electroporation markedly improves Sleeping Beauty transposon-induced tumorigenesis in mice.

The Sleeping Beauty (SB) transposon system is an important tool for genetic studies. It is used to insert a gene of interest into the host chromosome, thus enabling permanent gene expression. However, this system is less useful in higher eukaryotes because the transposition frequency is low. Efforts to improve the efficacy of the SB transposon system have focused on the method of gene delivery, but although electroporation has recently attracted much attention as an in vivo gene delivery tool, the simultaneous use of electroporation and the SB transposon system has not been studied for gene transfer in mice. In this study, electroporation was used in a model of SB transposon-induced insertional tumorigenesis. Electroporation increased the rate of tumor development to three times that of the control group. There was no difference in phenotype between tumors induced with the SB transposon system alone and those induced by the SB transposon and electroporation. Electroporation therefore may be an efficient means of improving the efficacy of gene transfer via the SB transposon system.

Inflammatory responses and morphological changes of radiofrequency-induced rat sciatic nerve fibres.

BACKGROUND: Recently, the pulsed radiofrequency (PRF, pulsed fashion) procedure was introduced for neuropathic pain management. Since PRF-induced lesions do not need high temperature compared with conventional continuous RF (CRF)-induced lesions, there is no significant loss of sensory fibres after application. METHODS: The progressive changes in the expression of eight representative inflammatory cytokines - glial fibrillary acidic protein, tumour necrosis factor alpha, interleukin-6, cyclooxygenase-II, inducible nitric oxide synthase, nuclear factor-κB, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α - as well as the morphological changes in extracellular matrices by Masson's trichrome and Verhoeff-van Gieson staining and atomic force microscopy were assessed for normal (control), sham (no RF current), PRF and CRF (positive control) rats. The RF procedure used in this study was similar to the methods used in human clinical trials. RESULTS: All proposed inflammatory proteins showed up-regulation after RF thermal treatments. Specifically, PRF-treated rats showed recovery of up-regulated inflammatory cytokines on day 30 after application, while CRF rats showed significant up-regulation that persisted until day 30. The control and sham groups showed normal unmyelinated axon and collagen structures. PRF-induced lesions showed less fibre destruction than CRF-induced lesions. PRF-induced lesions also showed mild axonal damage and little swelling of the mitochondria. CRF-induced lesions showed ultrastructural changes of sciatic nerve fibres that were irreversible. CONCLUSIONS: PRF-induced pain relief may be due to temporary blockage of nerve signals through the nerve pathway responsible for reversible neuronal depression. However, CRF-induced pain relief may be due to permanent blockage of nerve signals through other nerve pathways. Therefore, CRF could be applied to chronic inflammatory models used to study the mechanism of neuropathic pain.

Mid-long term effect of non-ablative high radiofrequency therapy on the rabbit dermal extracellular matrix.

This study quantitatively investigated the postoperative effects of radiofrequency (RF) application on the normal dermal extracellular matrix (ECM) of in vivo rabbits. Postoperative effects were evaluated by histology and atomic force microscopy analysis of dermal tissues treated using three RF energy levels (10 ~ 30 W) and either a single- or multiple-pass procedure. Progressive changes in the morphology of rabbit dermal ECMs were investigated over a 30-day postoperartive period. All RF-treated groups, except for the low energy group (10 W), displayed more prominent inflammatory responses compared to the control. This inflammatory reaction was more prominent a day after application. Dermal tissues 30 days after RF application exhibited prominent myofibroblast activity associated with ECM contractile activity during wound healing in addition to chronic inflammation. A decrease in the morphology of dermal ECMs after RF application continued until seven days postoperatively. The ECM diameter increased to near baseline at 30 days postoperatively. Low energy and multi-pass applications resulted in greater collagen fibril contraction and recovery at the ultra-structural level at 30 days postoperatively than did a single high energy application.

Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy.

Adenoviruses (Ad) have been investigated for their efficacy in reducing primary tumors after local intratumoral administration. Despite high Ad concentrations and repetitive administration, the therapeutic efficacy of Ad has been limited because of rapid dissemination of the Ad into the surrounding normal tissues and short maintenance of Ad biological activity in vivo. To maximize the therapeutic potential of Ad-mediated gene therapeutics, we investigated the efficacy of local, sustained Ad delivery, using an injectable alginate gel matrix system. The biological activity of Ad loaded in alginate gel was prolonged compared with naked Ad, as evidenced by the high green fluorescent protein gene transduction efficiency over an extended time period. Moreover, oncolytic Ad encapsulated in alginate gel elicited 1.9- to 2.4-fold greater antitumor activity than naked Ad in both C33A and U343 human tumor xenograft models. Histological and quantitative PCR analysis confirmed that the oncolytic Ad/alginate gel matrix system significantly increased preferential replication and dissemination of oncolytic Ad in a larger area of tumor tissue in vivo. Taken together, these results show that local sustained delivery of oncolytic Ad in alginate gel augments therapeutic effect through selective infection of tumor cells, sustained release and prolonged maintenance of Ad activity.

Oral health status of male adolescent smokeless tobacco users in Saudi Arabia.

Few studies have evaluated the oral effects of smokeless tobacco use in adolescents. This study described the oral health status of adolescents who were daily users of local smokeless tobacco (shamma) in Saudi Arabia. A convenience sample of 270 middle-school male students completed a questionnaire and received an oral examination and a saliva cotinine test. Among the students, 96% had plaque deposits (mean plaque index score 1.66); 41% had gingivitis (mean clinical attachment loss 1.1 mm); 56% had dental caries (mean decayed, missing, filled teeth score 2.1) and 86% had at least I mucosal lesion. The levels of plaque, gingivitis, dental caries and periodontitis among smokeless tobacco users were similar to those of most adolescents regardless of tobacco use. Almost 9/10 students had a mucosal lesion that could be related to smokeless tobacco use. Strong measures should be taken to increase students' awareness of the adverse health effects of tobacco use and to control their access to tobacco.

Association of CXCL1 promoter polymorphism with ischaemic stroke in Korean population.

This is a pilot study analysing association of chemokine gene polymorphisms (CXCL1, rs3117604; CXCL2, rs3806792; CCL2, rs2857656 and rs3760396; CCL5, rs2107538) in Korean patients with ischemic stroke (IS) (n = 120) and age-matched controls (n = 267). The CXCL1 gene and particularly T allele of rs3117604 was associated with IS.

Utility of Basal luteinizing hormone levels for detecting central precocious puberty in girls.

The hallmark of puberty is the progressive increase in gonadotropin-releasing hormone (GnRH) activity, reflected by an increase in the circulating concentration of luteinizing hormone (LH). The GnRH stimulation test is widely used in the evaluation of precocious puberty. The aim of our study was to assess the diagnostic utility of basal LH for the diagnosis of central precocious puberty (CPP) in girls. A total of 803 girls were referred to Ajou University Hospital for evaluation of precocious puberty between 2008 and 2011. All subjects underwent GnRH-stimulation tests as part of their evaluation. Serum LH and follicle stimulating hormone (FSH) were measured by immunoradiometric assay before and after the GnRH injection. Of the 803 subjects, 505 (62.9%) were included in the pubertal response group and 298 (37.1%) were in the prepubertal response group. Basal LH level was identified as a significant predictor for CPP. Based on the ROC curve, the optimal cut off point of basal LH related to 'pubertal response' was 1.1 IU/l, which was associated with 69.1% sensitivity and 50.5% specificity, with an area under the ROC curve of 0.620 (95% CI, 0.581-0.660). It is concluded that a single basal LH measurement can be used as a screening test to identify girls with CPP and to determine who should undergo GnRH stimulation test.

Marker-free registration for the accurate integration of CT images and the subject's anatomy during navigation surgery of the maxillary sinus.

OBJECTIVE: This study compared three marker-free registration methods that are applicable to a navigation system that can be used for maxillary sinus surgery, and evaluated the associated errors, with the aim of determining which registration method is the most applicable for operations that require accurate navigation. METHODS: The CT digital imaging and communications in medicine (DICOM) data of ten maxillary models in DICOM files were converted into stereolithography file format. All of the ten maxillofacial models were scanned three dimensionally using a light-based three-dimensional scanner. The methods applied for registration of the maxillofacial models utilized the tooth cusp, bony landmarks and maxillary sinus anterior wall area. The errors during registration were compared between the groups. RESULTS: There were differences between the three registration methods in the zygoma, sinus posterior wall, molar alveolar, premolar alveolar, lateral nasal aperture and the infraorbital areas. The error was smallest using the overlay method for the anterior wall of the maxillary sinus, and the difference was statistically significant. CONCLUSION: The navigation error can be minimized by conducting registration using the anterior wall of the maxillary sinus during image-guided surgery of the maxillary sinus.

Evaluation of overnight storage conditions for autologous peripheral blood stem cell products: comparison of three different conditions.

BACKGROUND: Overnight (ON) storage of peripheral blood stem cell (PBSC) occurs frequently in clinical settings. However, there are no standard guidelines for optimal storage conditions of freshly harvested PBSC. The aim of this study was to investigate the influence of storage temperatures on the quality of autologous PBSC and establish optimal storage conditions before cryopreservation. METHODS: A retrospective analysis was performed on 260 PBSC harvests according to pre-cryopreservation conditions: immediate processing or ON storage at room temperature (RT). For direct comparison, 30 autologous PBSC products were collected prospectively and prepared under three different pre-cryopreservation conditions: immediate processing, ON storage at 4°C and ON storage at RT. The recovery of CD34(+) cells, post-thaw CFU-GM count and viability were analysed. RESULTS: Retrospective analysis revealed that post-thaw CFU-GM count was significantly lower when PBSC were stored ON at RT compared to when immediately processed (136·4 vs. 409·6/µl). Prospective analysis showed a mean recovery of CD34(+) cells of 65·5 ± 25·1%, 70·5 ± 27·4% and 35·9 ± 25·1% for immediate processing, ON storage at 4°C and ON storage at RT, respectively. Similarly, mean viability and CFU-GM counts were significantly reduced when stored ON at RT compared to when immediately processed or stored ON at 4°C (60·4 ± 25·6 vs. 84·1 ± 12·9 vs. 82·7 ± 12·6%, 15·7 ± 25·7 vs. 398·5 ± 906·2 vs. 350·0 ± 847·9/µl, respectively). CONCLUSIONS: ON storage of autologous PBSC at RT significantly decreased the quality of HPCs. These data indicate that ON storage of autologous PBSC at 4°C would be the most reasonable approach for maintaining the quality of HPCs when immediate processing is not possible.

Factors affecting tobacco use among middle school students in Saudi Arabia.

A rapid rise in the number of tobacco users in Saudi Arabia has occurred in the past decade, particularly among the youth. This study identified socio-cultural determinants of tobacco use and explored possible approaches to prevent adolescents' tobacco use in Saudi Arabia. A cross-sectional survey was administered using a self-administered questionnaire for collecting information on risk and protective factors for tobacco use among middle school students. School selection was stratified by region, gender, and type (public or private). Of 1,186 7-9th grade students, 1,019 questionnaires were analyzed. Risk factors affecting tobacco use included all important others' perceptions; mother, sister, friend, teacher and important person's tobacco use; pressure to use tobacco from brother, sister, friend and important persons; easy access to tobacco and frequent skipping of classes. Protective factors for tobacco use included family's perception; friend, teacher and important person's tobacco use; parents' help; support from family, friends, and teachers; accessibility to tobacco; school performance and family income, father's education, and district of residence. The findings of this study show clear gender differences in social influences and attitudes towards tobacco use. Religious beliefs and access to tobacco products were significantly associated with attitudes towards tobacco use and future intention of use. Developing and implementing effective gender specific school-based tobacco prevention programs, strict reinforcement of tobacco control policies, and a focus on the overall social context of tobacco use are crucial for developing successful long-term tobacco prevention programs for adolescents.

HbA1c and glucose intolerance in obese children and adolescents.

AIMS: Childhood obesity is associated with an increased likelihood for having impaired glucose tolerance, dyslipidaemia and diabetes. The aim of the study was to evaluate HbA(1c) as a screening test for impaired glucose tolerance in obese children and adolescents and identify the optimal HbA(1c) threshold. METHODS: We studied 126 obese and overweight children (BMI > 85 th percentile for age and gender) 4-17 years of age referred to the endocrine clinic at Ajou University Hospital in Korea. All subjects underwent HbA(1c) and oral glucose tolerance test. RESULTS: Thirty-four patients (27%) out of 126 had impaired glucose tolerance. Silent diabetes was diagnosed in 10 adolescents (7.9%). Based on the receiver operating characteristic curve, the optimal cut point of HbA(1c) related to impaired glucose tolerance diagnosed by oral glucose tolerance test was 40 mmol/mol (5.8%), which was associated with a 64.7% sensitivity and 61.6% specificity, with an area under the receiver operating characteristic curve of 0.651 (95% CI 0.529-0.772). CONCLUSIONS: Obesity is associated with an increased risk of impaired glucose tolerance. An HbA(1c) value of 40 mmol/mol (5.8%) should be used as a screening tool to identify children and adolescents with impaired glucose tolerance.

Effects of self-ligating brackets on the surfaces of stainless steel wires following clinical use: AFM investigation.

In orthodontic treatment, the frictional force between the archwire and bracket reduces the effectiveness of orthodontic treatment. The frictional force is affected not only by the geometry of the self-ligating brackets but also by physical changes between the bracket slots and archwire surfaces during sliding movement. This study examined quantitatively the effect of self-ligating treatments on the surfaces of stainless steel (SS) archwires during tooth movement in vivo by atomic force microscopy. Orthodontic 0.019″ × 0.025″ SS archwires after clinical use with the first bicuspid-extraction treatment were employed using the Damon 3MX(®) SS self-ligating brackets, Clippy-C(®) ceramic self-ligating brackets, and Kosaka(®) SS brackets. Intact SS archwires were used as the control group. All SS archwires after clinical use showed severe scratches and significantly higher roughness caused by frictional interactions between the brackets and archwires (p < 0.0001 vs. control). The descending order of surface roughness was the SS archwires treated, with ceramic self-ligating brackets, with conventional SS brackets, and with SS self-ligating brackets (p < 0.001). These findings suggest that an orthodontic treatment with SS self-ligating brackets may require smaller orthodontic forces than that with ceramic self-ligating brackets or conventional SS brackets.