Elevated transglutaminase-2 expression mediates fibrosis in areca quid chewing-associated oral submucocal fibrosis via reactive oxygen species generation.

OBJECTIVES: Transglutaminase-2 (TGM-2) protein is involved in the cross-linking of matrix proteins resulting in several fibrotic disorders and can be induced by reactive oxygen species (ROS). Little is known about its role in the development of oral submucocal fibrosis (OSF). Hence, we hypothesize that TGM-2 may have a role in the pathogenesis of areca quid chewing-associated OSF and arecoline, a major areca nut alkaloid, could regulate TGM-2 via ROS generation. MATERIALS: Forty OSF specimens from areca quid chewing-associated OSF and ten normal buccal mucosa biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The expression of TGM-2 from fibroblasts cultured from OSF and normal buccal mucosa was evaluated by Western blot. The effect of arecoline on normal buccal mucosa fibroblasts (BMFs) was used to elucidate whether TGM-2 expression could be affected by arecoline by using 2', 7'-dichlorofluorescein diacetate assay and Western blot. In addition, glutathione precursor N-acetyl-L-cysteine (NAC) and epigallocatechin-3 gallate (EGCG) were added to find the possible regulatory mechanisms. RESULTS: TGM-2 expression was significantly higher in OSF specimens than normal specimens (p < 0.05). Fibroblasts derived from OSF were found to exhibit higher TGM-2 expression than BMFs in protein levels (p < 0.05). Arecoline significantly upregulated the intracellular ROS generation in a dose-dependent manner (p < 0.05). TGM-2 protein induced by arecoline was found in BMFs in a dose-dependent manner (p < 0.05). Treatment with NAC and EGCG markedly inhibited TGM-2 expression induced by arecoline (p < 0.05). CONCLUSIONS: Our results suggest that TGM-2 expression is significantly upregulated in OSF tissues from areca quid chewers. Arecoline-upregulated TGM-2 expression may be mediated by ROS generation. CLINICAL RELEVANCE: TGM-2 protein is upregulated in areca quid chewing-associated OSF. Using this in vitro model, antioxidants could inhibit arecoline-upregulated TGM-2 expression. NAC and EGCG may serve as a useful agent in controlling OSF.

Upregulation of Slug expression by cyclosporine A contributes to the pathogenesis of gingival overgrowth.

BACKGROUND/PURPOSE: Gingival overgrowth occurs as a side effect of systemic medication with immunosuppressant cyclosporine A (CsA). Slug, a master regulator of epithelial-mesenchymal transition, is dramatically upregulated in a variety of fibrotic diseases. The aim of this study is to investigate the role of epithelial-mesenchymal transition marker Slug in the pathogenesis of CsA-induced gingival overgrowth. METHODS: Clinically healthy gingiva and CsA-induced gingival overgrowth specimens were analyzed by immunohistochemistry. The effect of CsA on normal human gingival fibroblasts (HGFs) was used to elucidate whether Slug expression could be affected by CsA by real-time reverse transcription-polymerase chain reaction and western blot. Cell proliferation in CsA-treated HGFs with Slug lentiviral-mediated shRNAi knockdown was evaluated by tetrazolium bromide reduction assay. RESULTS: Slug expression was higher in CsA-induced gingival overgrowth specimens than in clinical healthy gingiva (p < 0.05). Slug expression was significantly higher in CsA-induced gingival overgrowth specimens with higher levels of inflammatory infiltrates (p < 0.05). CsA was found to increase Slug transcript and protein expression in HGFs in a dose-dependent manner (p < 0.05). In addition, knockdown of Slug significantly suppressed CsA-induced cell proliferation in HGFs (p < 0.05). CONCLUSION: Taken together, upregulation of Slug in HGFs stimulated by CsA may play an important role in the pathogenesis of CsA-induced gingival overgrowth.

Hypoxic regulation of plasminogen activator inhibitor-1 expression in human buccal mucosa fibroblasts stimulated with arecoline.

BACKGROUND: Oral submucous fibrosis (OSF) is regarded as a pre-cancerous condition with fibrosis in oral subepithelial connective tissue. Hypoxia-inducible factor (HIF)-1α regulates a wide variety of profibrogenic genes, which are closely associated with tissue fibrosis. The aim of this study was to compare HIF-1α expression in normal buccal mucosa tissues and OSF specimens and further explore the potential mechanisms that may lead to the induction of HIF-1α expression. METHOD: Twenty-five OSF specimens and six normal buccal mucosa were examined by immunohistochemistry. The expression of HIF-1α from fibroblasts cultured from OSF and normal buccal mucosa was measured by Western blot. Arecoline, a major areca nut alkaloid, was challenged to normal buccal mucosa fibroblasts (BMFs) to elucidate whether HIF-1α expression could affect by arecoline. In addition, the effects of arecoline on plasminogen activator inhibitor (PAI)-1 expression were evaluated in environmental hypoxia. RESULTS: HIF-1α expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, epithelial cells, and inflammatory cells. Fibroblasts derived from OSF were found to exhibit higher HIF-1α protein expression than BMFs (P < 0.05). Arecoline was found to upregulate HIF-1α protein in a dose-dependent manner (P < 0.05). Hypoxia increased arecoline-induced PAI-1 protein expression than normoxic conditions (P < 0.05). CONCLUSION: These results suggest that HIF-1α expression is significantly upregulated in OSF tissues from areca quid chewers, implying a potential role as a biomarker for local tissue hypoxia. The activation of HIF-1α may promote fibrogenesis by an increase of PAI-1 expression and a subsequent elevation of extracellular matrix production in oral submucosa leading to fibrosis.

Complementary usage of Rhodiola crenulata (L.) in chronic obstructive pulmonary disease patients: the effects on cytokines and T cells.

Although chronic obstructive pulmonary disease (COPD) is an inflammatory disease predominantly involving T cells, no study of Rhodiola as an immunomodulator in COPD patients has been reported. In this study, COPD patients took Rhodiola crenulata 500 mg (n = 38) or placebo (starch/phosphate buffered saline) (n = 19) daily for 12 weeks and were compared with untreated, age-matched, and sex-matched non-COPD control subjects. Our results showed that serum levels of IL-2, IL-10, and IFN-γ in COPD patients before treatment are significantly higher than levels in non-COPD controls (p < 0.05). A significant decrease in IFN-γ was seen in the Rhodiola treatment group (p < 0.05) but not in the placebo group (p > 0.05). The results suggested that Rhodiola treatment had beneficial antiinflammation effects, lower COPD assessment test score and decreased high-sensitivity C-reactive protein, on COPD patients (p < 0.05). The effects of Rhodiola treatment on COPD patients were shown to decrease the IFN-γ concentration and CD8(+) count but increase the expressions of CD4(+) CD25(+) FOXP3(+) and CD4(+) CD25(+) CD45(+) FOXP3(+) in the blood significantly (p < 0.05). This is the first trial using Rhodiola as a complementary therapy for COPD patients. T cells play an important role in the pathogenesis of COPD through the increased expression of CD8(+) T cells and IFN-γ and may be a viable target for potential therapy.

The modulation of hypoxia-inducible factor-1α/plasminogen activator inhibitor-1 axis in human gingival fibroblasts stimulated with cyclosporine A.

BACKGROUND/PURPOSE: The prominent side effect of the immunosuppressive drug cyclosporine A (CsA) is gingival overgrowth. Hypoxia-inducible factor (HIF)-1α regulates a wide variety of profibrogenic genes, which are closely associated with tissue fibrosis. The aim of this study was to compare HIF-1α expression in normal gingival tissues and CsA-induced gingival overgrowth specimens and further explore the potential mechanisms that may lead to induction of HIF-1α expression. METHODS: Fifteen CsA-induced gingival overgrowth specimens and five normal gingival tissues were examined by immunohistochemistry. Western blot was used to investigate the effects of CsA on the expression of HIF-1α in cultured human gingival fibroblasts. The effects of CsA on plasminogen activator inhibitor (PAI)-1 expression were evaluated in environmental hypoxia. RESULTS: HIF-1α staining in gingival tissue was stronger in CsA-induced gingival overgrowth group than normal gingival group (p < 0.05). The expression of HIF-1α was significantly higher in CsA-induced gingival overgrowth specimens with higher levels of inflammatory infiltrates (p = 0.041). CsA was found to upregulate HIF-1α protein in a dose-dependent manner (p < 0.05). Hypoxia increased CsA-induced PAI-1 protein expression than normoxic conditions (p < 0.05). CONCLUSION: These results suggest that HIF-1α expression is significantly upregulated in CsA-induced gingival overgrowth specimens. The activation of HIF-1α may promote fibrogenesis by an increase of PAI-1 expression and a subsequent elevation of extracellular matrix production in gingival tissues.

Arecoline-induced myofibroblast transdifferentiation from human buccal mucosal fibroblasts is mediated by ZEB1.

Oral submucous fibrosis (OSF) is considered as a pre-cancerous condition of the oral mucosa and is highly associated with habitual areca quid chewing. Arecoline is the major alkaloid in areca quid and is thought to be involved in the pathogenesis of OSF. Our previous studies have demonstrated that arecoline could induce epithelial-mesenchymal transition (EMT)-related factors in primary human buccal mucosal fibroblasts (BMFs). Therefore, we investigated the expression of zinc finger E-box binding homeobox 1 (ZEB1), which is a well-known transcriptional factor in EMT, in OSF tissues and its role in arecoline-induced myofibroblast transdifferentiation from BMFs. The expression of ZEB1, as well as the myofibroblast marker α-smooth muscle actin (α-SMA), was significantly increased in OSF tissues, respectively. With immunofluorescence analysis, arecoline induced the formation of α-SMA-positive stress fibres in BMFs expressing nuclear ZEB1. Arecoline also induced collagen contraction of BMFs in vitro. By chromatin immunoprecipitation, the binding of ZEB1 to the α-SMA promoter in BMFs was increased by arecoline. The promoter activity of α-SMA in BMFs was also induced by arecoline, while knockdown of ZEB1 abolished arecoline-induced α-SMA promoter activity and collagen contraction of BMFs. Long-term exposure of BMFs to arecoline induced the expression of fibrogenic genes and ZEB1. Silencing of ZEB1 in fibrotic BMFs from an OSF patient also suppressed the expression of α-SMA and myofibroblast activity. Inhibition of insulin-like growth factor receptor-1 could suppress arecoline-induced ZEB1 activation in BMFs. Our data suggest that ZEB1 may participate in the pathogenesis of areca quid-associated OSF by activating the α-SMA promoter and inducing myofibroblast transdifferentiation from BMFs.

Selective apoptotic cell death effects of oral cancer cells treated with destruxin B.

BACKGROUND: Recent studies have revealed that destruxins (Dtx) have potent cytotoxic activities on individual cancer cells, however, data on oral cancer cells especial human are absent. METHODS: Destruxin B (DB) was isolated and used to evaluate the selective cytotoxicity with human oral cancer cell lines, GNM (Neck metastasis of gingival carcinoma) and TSCCa (Tongue squamous cell carcinoma) cells, and normal gingival fibroblasts (GF) were also included as controls. Cells were tested with different concentrations of DB for 24, 48, and 72 h by MTT assay. Moreover, the mechanism of cytotoxicity was investigated using caspase-3 Immunofluorescence, annexin V/PI staining, and the expression of caspase-3, Bax, and Bcl-2 by western blotting after treated with different concentrations of DB for 72 h as parameters for apoptosis analyses. RESULTS: The results show that DB exhibited significant (p < 0.01) and selective time- and dose-dependent inhibitory effects on GNM and TSCCa cells viability but not on GF cells. The data suggested that DB is capable to induce tumor specific growth inhibition in oral GNM and TSCCa cancer cells via Bax/Bcl-2-mediated intrinsic mitochondrial apoptotic pathway in time- and dose-dependent manners. CONCLUSIONS: This is the first report on the anti-proliferation effect of DB in oral cancer cells. The results reported here may offer further evidences to the development of DB as a potential complementary chemotherapeutic target for oral cancer complications.

Management of radicular cysts using platelet-rich fibrin and bioactive glass: a report of two cases.

Platelet-rich fibrin (PRF) created by Choukroun's protocol concentrates most platelets and leukocytes from a blood harvest into a single autologous fibrin biomaterial. However, no current data is available concerning the use of PRF for the treatment of periapical lesions. Two cases of radicular cysts were reported using an interdisciplinary approach, including regular endodontic therapy followed by surgical management with PRF and bioactive glass. Two cases of radicular cysts presented as an incidental radiographic finding, appearing as an apical radiolucency with well-circumscribed sclerotic borders. After regular endodontic retreatment, cystic lining/granulation tissues were enucleated and the periradicular bony defect was grafted using PRF and bioactive glass. Then, PRF was applied to serve as a membrane over the grafted defects. Recall periapical radiographs of Case 1 and cone beam computer tomography of Case 2 showed satisfactory healing of the periapical pathosis. In Case 2, the bony defect appeared completely healed at 4 months surgical reentry and the new bone was clinically very dense and mature. The results of these case reports show that the combination of PRF and bioactive glass is an effective modality of regenerative treatment for radicular cysts.

Remote Diagnosis on Upper Respiratory Tract Infections Based on a Neural Network with Few Symptom Words-A Feasibility Study.

This study aims explore the feasibility of using neural network (NNs) and deep learning to diagnose three common respiratory diseases with few symptom words. These three diseases are nasopharyngitis, upper respiratory infection, and bronchitis/bronchiolitis. Through natural language processing, the symptom word vectors are encoded by GPT-2 and classified by the last linear layer of the NN. The experimental results are promising, showing that this model achieves a high performance in predicting all three diseases. They revealed 90% accuracy, which suggests the implications of the developed model, highlighting its potential use in assisting patients' understanding of their conditions via a remote diagnosis. Unlike previous studies that have focused on extracting various categories of information from medical records, this study directly extracts sequential features from unstructured text data, reducing the effort required for data pre-processing.

Healthcare Outcomes of Patients and Antecedents via Teleophthalmology in Eastern Taiwan during COVID-19.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has caused significant transformations in healthcare. Many countries began the rapid development and adoption of telemedicine to avoid the spread of the pandemic and created an innovative model for healthcare delivery. This study identified the critical antecedents that affected the considered healthcare outcomes via teleophthalmology in Eastern Taiwan during the COVID-19 pandemic. METHODS: This study's participants included residents of five towns in Taitung County who had experience with teleophthalmology. This study analyzed the structured questionnaires completed by the participants to validate the proposed research framework. Statistical methods were used to verify the research models, including descriptive statistical analysis, confirmatory factor analysis, and structural equation modeling. The date of this study was from 1 October 2020 to 31 July 2023. RESULTS: The results of this study reveal that the average monthly use of teleophthalmology by individuals in rural areas increased annually. Females tended to utilize teleophthalmology services more than males. There were no significant differences across any of the constructs with respect to age or educational level. Additionally, the patients' awareness of healthcare accessibility via and the communication quality of teleophthalmology simultaneously affected teleophthalmology's adoption and service quality, which in turn jointly affected health outcomes. Both healthcare accessibility and communication quality were the antecedents of the healthcare outcomes. The health outcomes refer to the impact of teleophthalmology on the quality of the patients' health and well-being. Additionally, teleophthalmology's adoption and service quality acted as mediators. CONCLUSIONS: This study's findings are expected to increase attention to the healthcare outcomes and antecedents of teleophthalmology to promote better telemedicine practices and services for rural residents.

The expression of O(6) -methylguanine-DNA methyltransferase in human oral keratinocytes stimulated with arecoline.

BACKGROUND: O(6) -methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that can protect cells from carcinogenic effects of alkylating agents by removing adducts from the O(6) position of guanine. Evidences indicated that areca quid chewing may increase the risk of oral squamous cell carcinoma (OSCC). This study was to investigate the role of MGMT expression in OSCCs and the normal oral tissues. METHODS: Thirty-two OSCCs from areca quid chewers and ten normal oral tissue biopsy samples without areca quid chewing were analyzed by the immunohistochemistry for MGMT. Primary human oral keratinocytes (HOKs) were challenged with arecoline, the major alkaloid of areca nut, by Western blot. Nicotine, an important component of cigarette smoke, was added to find the possible regulatory mechanisms. RESULTS: Significant association was observed between low MGMT expression and advanced clinical stage of OSCCs and lymph node metastasis (P = 0.03). MGMT expression was significantly higher in patients only chewing areca quid than patients both chewing areca quid and smoking (P = 0.028). Arecoline was found to elevate MGMT expression in a dose- and time-dependent manner. The addition of nicotine was found to enhance arecoline-induced MGMT expression. CONCLUSION: Our results indicate that MGMT could be used clinically as a predictive marker for tumor processing, the potential for lymph node metastasis as well as advanced clinical stage. MGMT expression was significantly upregulated by arecoline in HOKs. Nicotine has a synergistic effect of arecoline-induced MGMT expression. The cigarette smoking may act synergistically in the pathogenesis of OSCC in areca quid chewers via the upregulation of MGMT.

Exploration of COVID-19 Pandemic Prevention Behaviors among Healthcare Workers.

Since the outbreak of COVID-19, the pandemic has become an important topic of global public health. To reduce the rapid spread of the pandemic, compliance with preventive behaviors has become one of the important guidelines from the World Health Organization (WHO). Healthcare workers stand on the frontline for pandemic prevention, and preventive behaviors are essential measures to protect their health and safety. The purpose of this study was to propose an integrative model that explained and predicted COVID-19 preventive behaviors among healthcare workers. The study integrated workplace safety climate and the health belief model (HBM) to verify the impact of workplace safety climate and health belief factors on the safety attitude, safety compliance, and safety satisfaction of healthcare workers performing COVID-19 pandemic prevention behaviors. A cross-sectional study was conducted from March to August 2021 with a self-administered online questionnaire. The sample of the study was drawn from healthcare workers of a famous medical institution in Taipei City as research subjects. After collecting 273 valid questionnaires and verifying them through the analysis of structural equation modeling (SEM), the findings revealed that workplace safety climate had an impact on health belief factors, and then health belief factors had impacts on safety attitudes. In addition, safety attitude affected safety compliance, while safety compliance further affected safety satisfaction. The study showed that workplace safety climate can strengthen healthcare workers' health beliefs and further affect their safety attitudes, safety compliance, and safety satisfaction. The study attempted to propose a model of healthcare workers' pandemic prevention behaviors as a reference for medical facility administrators in real practice.

ß-catenin expression in areca quid chewing-associated oral squamous cell carcinomas and upregulated by arecoline in human oral epithelial cells.

BACKGROUND/PURPOSE: Nuclear localization of ß-catenin is known to associate with malignant transformation of many squamous cell carcinomas. The aim of this study was to compare ß-catenin expression in normal human oral epithelium and areca quid chewing associated oral squamous cell carcinomas (OSCCs) and further to explore the potential mechanisms that may lead to induce ß-catenin expression. METHODS: A total of 40 areca quid chewing-associated OSCCs and 10 normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line GNM cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, extracellular signal-regulated protein kinase inhibitor PD98059, glutathione precursor N-acetyl-l-cysteine (NAC), tyrosine kinase inhibitor herbimycin-A, p38 inhibitor SB203580, and phosphatidylinositaol 3-kinase inhibitor LY294002 were added to find the possible regulatory mechanisms. RESULTS: ß-catenin expression was significantly higher in OSCC specimens than that in normal oral epithelial specimens (p < 0.05). It was demonstrated that normal oral epithelium showed only membranous staining for ß-catenin, and membranous staining was lost or reduced with an increase in cytoplasmic/nuclear staining in OSCCs. Arecoline was found to elevate ß-catenin expression in a dose-dependent manner (p < 0.05). The addition of PD98059, NAC, herbimycin-A, SB203580, and LY294002 markedly inhibited the arecoline-induced ß-catenin expression (p < 0.05). CONCLUSION: ß-catenin expression is significantly upregulated in areca quid chewing-associated OSCC. The localization of ß-catenin expression is correlated with the tumor size and clinical stage. In addition, ß-catenin expression induced by arecoline is downregulated by PD98059, NAC, herbimycin-A, SB203580, and LY294002.

Determinants of Telehealth Continuance Intention: A Multi-Perspective Framework.

Owing to the COVID-19 pandemic, many countries' physicians in the world have used telehealth to visit patients via telehealth. The study aimed to integrate the theory of planned behavior (TPB), the technology acceptance model (TAM), and self-determination theory (SDT) to explore the adoption behavior of a telehealth system. A convenient sample of residents was drawn from the population of Nantou County in Taiwan and analyzed via structural equation modeling. The findings revealed that attitude, perceived behavioral control, perceived usefulness, and perceived autonomy support jointly have significantly positive effects on continuance intention. Results also confirmed that perceived autonomy support, perceived ease of use, and perceived usefulness jointly have significantly positive effects on attitude. Furthermore, this study also showed that a crucial mediators' role is played by perceived ease of use, perceived usefulness, and attitude. The conclusions and practical implications of the research will hopefully provide health organizations and institutions with some innovative insights and foresights, which in turn will promote better practices and services of telehealth technology.

Antioxidative and hepatoprotective effects of fructo-oligosaccharide in d-galactose-treated Balb/cJ mice.

Chronic subcutaneous (s.c.) administration of d-galactose (DG) to BL/6J mice has been shown to induce oxidative stress and is considered a model to mimic accelerated ageing. Fructo-oligosaccharide (FO) is a well-defined prebiotic and its fermentation by lactic acid bacteria has been shown to exert antioxidative capacity. The present study was aimed to determine whether FO attenuated DG-induced oxidative stress and hepatopathy in Balb/cJ mice. Mice (12 weeks of age, n 40) were divided into control (s.c. saline), DG (s.c. 1·2 g/kg body weight), DG+FO (5%, w/w) and DG+vitamin E (0·2%, w/w) groups and were killed after 52 d of treatment. Results indicated that DG significantly decreased the hepatic superoxide dismutase and glutathione peroxidase activities. These alterations were ameliorated both by FO and vitamin E. DG increased the hepatic TAG content approximately by 7·2% compared with the vehicle control, which was in agreement with the histological alteration. FO, similar to vitamin E, almost normalised the hepatic TAG content and ameliorated the histological characteristics of fatty liver. Similarly, the increased plasma alanine aminotransferase activity induced by DG was normalised by FO and vitamin E, respectively. Faecal bifidobacteria counts were greater in the DG+FO and DG+vitamin E groups compared with the DG group, respectively. In conclusion, the present study indicated that FO diminished the altered hepatic antioxidative enzyme activities and morphology caused by chronic DG administration in Balb/cJ mice, partially associated with its prebiotic role in the colon.

Heat shock protein 47 expression in oral squamous cell carcinomas and upregulated by arecoline in human oral epithelial cells.

BACKGROUND: Heat shock protein 47 (HSP47) is a product of CBP2 gene located at chromosome 11q13.5, a region frequently amplified in human cancers. Areca quid chewing is a major risk factor of oral squamous cell carcinoma (OSCC). The aim of this study was to compare HSP47 expression in normal human oral epithelium and OSCC and further to explore the potential mechanisms that may lead to induce HSP47 expression. METHODS: Thirty-two OSCC specimens and ten normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line OC2 cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, glutathione precursor N-acetyl-l-cysteine (NAC), extracellular signal-regulated protein kinase (ERK) inhibitor PD98059, phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, cyclooxygenase-2 inhibitor NS-398, and tyrosine kinase inhibitor herbimycin A were added to find the possible regulatory mechanisms. RESULTS: HSP47 expression was significantly higher in OSCC specimens than normal epithelium (P<0.05). No significant difference in HSP47 expression was observed with respect to age, sex, T category, stage, and differentiation (P>0.05). The lower HSP47 expression was associated with lymph node metastasis (P=0.015). Arecoline was found to elevate HSP47 expression in a dose- and time-dependent manner (P<0.05). The addition of NAC, PD98059, LY294002, NS398, and herbimycin A markedly inhibited the arecoline-induced HSP47 expression (P<0.05). CONCLUSION: Our findings demonstrated that HSP47 expression is significantly upregulated in areca quid chewing-associated OSCCs. HSP47 could be used clinically as a marker for lymph node metastasis of oral carcinogenesis. In addition, arecoline-induced HSP47 expression was downregulated by NAC, PD98059, LY294002, NS398, and herbimycin A.

[The development and effectiveness of telecare from an integrated technological, humanistic and management perspective].

A decreasing birthrate coupled with a growing elderly population has lead to an increased focus on elderly-centric issues such as long-term care and senior healthcare. Recent advances in information, communication and biomedical technologies have combined to allow the development of various types of telemedicine technology designed to enhance or expand patient services and care. To date, most telecare studies have focused on the development of underlying technologies rather than on patient (customer) perceptions regarding service mechanisms. The lack of the latter makes obtaining an effective understanding of the actual needs and problems of the elderly population difficult, and limits the potential for clinical implementation of study findings and further knowledge development. This article reviews important articles in the literature on telecare and evaluates the effectiveness of telecare-related technologies. Three key aspects associated with eight sub-indictors were identified. These included the aspects of technology (system quality); humanism (institutional trust and privacy risk); and management (service quality, cost benefit, satisfaction, use intention, and influence on health). An integrated perspective combining social and technological aspects is needed to facilitate increasing utilization of and satisfaction with telecare. Simply implementing new systems built around this innovative technology is not sufficient, and may be counterproductive. This article was written to help stimulate deeper exploration and insights into academic theory and clinical practice in order to help shape and create a better vision of aging in place.

A Model for Promoting Occupational Safety and Health in Taiwan's Hospitals: An Integrative Approach.

Advocating for improving workplace safety and health has gained substantial support in recent years. The medical industry is a high-risk industry and receives considerable public attention. This study used an integrative approach as a starting point and combined the contextual factors of an organization: perceived organizational support, safety climate, social influence, and shared decision making. Subsequently, the effects of these factors on preventive action and safety satisfaction were investigated. This study surveyed employees of two hospitals, one in Northern Taiwan and one in Eastern Taiwan, collecting valid data from 468 respondents. Structural equation modeling (SEM) was used to verify our research framework. The finding indicates that (1) All hypotheses proposed in this study were supported. (2) The overall goodness of fit of the model was excellent, and the explained variance of the outcome variables was high. (3) Safety climate had the strongest total effects on preventive action and safety satisfaction simultaneously, whereas preventive action had the strongest direct effect on safety satisfaction. The objective of this study was to obtain empirical conclusions and make suggestions for academic theory and clinical practice. The findings may serve as a reference for future research and for scholars and practitioners, enabling the creation of healthy workplaces and, thus, a brighter future.

The upregulation of metallothionein-1 expression in areca quid chewing-associated oral squamous cell carcinomas.

Metallothioneins (MTs) are a family of low molecular weight, cysteine-rich, inducible, intracellular proteins that bind heavy metals with high affinity. MT-1 is known as a stress-inducible protein and functions as an antioxidant enzyme. Areca quid chewing is a major risk factor in the development and further progression of oral squamous cell carcinoma (OSCC). The aim of this study was to compare MT-1 expression in normal human oral epithelium and OSCC and further explore the potential mechanism that may lead to induce MT-1 expression. Thirty four OSCC and 10 normal epithelium specimens were examined by immunohistochemistry and analyzed by the clinico-pathological profiles. The oral epithelial cell line GMN cells were challenged with arecoline, a major areca nut alkaloid, by reverse-transcriptase polymerase chain reaction. Furthermore, tobacco smoke carcinogen benzo[a]pyrene (BaP) and glutathione (GSH) precursor N-acetyl-l-cysteine (NAC) were added to find the possible regulatory mechanisms. The results from immunohistochemistry demonstrated that MT-1 expression was significantly higher in OSCC specimens (p<0.05). No significant difference in MT-1 expression was observed with respect to age, sex, T category, and stage (p>0.05). The high MT-1 expression was associated with lymph node metastasis (p=0.012). In addition, arecoline was found to elevate MT-1 mRNA in a dose-dependent manner (p<0.05). Furthermore, the addition of BaP enhanced the arecoline-induced MT-1 expression (p<0.05). The addition of NAC markedly inhibited the arecoline-induced MT-1 expression (p<0.05). These results lead to the conclusion that MT-1 expression is significantly upregulated in areca quid chewing associated-OSCC. The expression profile suggests MT-1 could be used clinically as a marker for tumors possessing the potential for lymph node metastasis. The compounds of tobacco products may act synergistically in the pathogenesis of OSCC in areca quid chewers. The regulation of MT-1 expression induced by arecoline is critically dependent on the intracellular GSH concentration.