Publications by authors named "Yi-Shing Shieh"

89 Publications

YAP-Dependent BiP Induction Is Involved in Nicotine-Mediated Oral Cancer Malignancy.

Cells 2021 Aug 13;10(8). Epub 2021 Aug 13.

Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan.

Cigarette smoking is a significant risk factor for the development and progression of oral cancer. Previous studies have reported an association between nicotine and malignancy in oral cancer. Recent studies have also demonstrated that nicotine can induce endoplasmic reticulum (ER) stress in tumor cells. Binding immunoglobulin protein (BiP) acts as a master regulator of ER stress and is frequently overexpressed in oral cancer cell lines and tissues. However, the effect of nicotine on BiP in oral cancer is unknown. Therefore, this study aimed to evaluate the role of BiP and its underlying regulatory mechanisms in nicotine-induced oral cancer progression. Our results showed that nicotine significantly induced the expression of BiP in time- and dose-dependent manners in oral squamous cell carcinoma (OSCC) cells. In addition, BiP was involved in nicotine-mediated OSCC malignancy, and depletion of BiP expression remarkably suppressed nicotine-induced malignant behaviors, including epithelial-mesenchymal transition (EMT) change, migration, and invasion. In vivo, BiP silencing abrogated nicotine-induced tumor growth and EMT switch in nude mice. Moreover, nicotine stimulated BiP expression through the activation of the YAP-TEAD transcriptional complex. Mechanistically, we observed that nicotine regulated YAP nuclear translocation and its interaction with TEAD through α7-nAChR-Akt signaling, subsequently resulting in increased TEAD occupancy on the HSPA5 promoter and elevated promoter activity. These observations suggest that BiP is involved in nicotine-induced oral cancer malignancy and may have therapeutic potential in tobacco-related oral cancer.
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http://dx.doi.org/10.3390/cells10082080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392082PMC
August 2021

Risk assessment of labial bone perforation in the anterior mandibular region: a virtual immediate implant placement study.

Int J Implant Dent 2021 Jul 26;7(1):68. Epub 2021 Jul 26.

Department of Periodontology, School of Dentistry, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.

Background: This study investigated the prevalence of labial bone perforation (LBP) related to the associated anatomic factors in anterior mandibular region using a virtual immediate implant placement procedure.

Methods: Series qualified CBCT images of 149 participants (894 teeth) were selected to analyze the assigned anatomical parameters, including concavity depth, concavity angle, torque, and deep bone thickness. Four classes of crestal and radicular dentoalveolar bone phenotypes (CRDAPs) of mandibular anterior teeth were categorized according to the thickness of dentoalveolar bone at both crestal and radicular zones. Data were adjusted for categorical (gender and CRDAP) and continuous (age, cavity angle, cavity depth, and deep bone thickness) variables using a multivariable logistic regression analysis with generalized estimating equation method.

Results: The overall probability of LBP after virtual implant placement was 21.6%. There is statistically significant higher prevalence of LBP at canine (28.5%) and CRDAP class II (29.2%) regions (p < 0.001). After adjusting confounding variables, CRDAP class II and class IV regions are more likely to have LBP when compared with CRDAP class I (control) regions (p < 0.01). The risk of LBP at canine site is 6.31 times more likely than at the central incisor (control) (p < 0.01).

Conclusions: Using a virtual immediate implant placement technique, the prevalence of LBP is significantly higher at the mandibular canine site and thin radicular dentoalveolar phenotype in the anterior mandibular region.
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http://dx.doi.org/10.1186/s40729-021-00351-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310813PMC
July 2021

A bibliometric analysis of top 100 most-cited articles in dentistry with author(s) affiliated with Taiwan institutes.

J Chin Med Assoc 2021 Aug;84(8):799-807

School of Dentistry, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan, ROC.

Background: Citation analysis can provide a historical perspective in the advancement of research, evolution, and areas of research. Taiwan exhibits rigorous academic and scientific activities in dentistry; however, based on its empirical contribution in research, there is no report in the literature analyzing the top-cited articles published by authors affiliated with Taiwan institutes. The purpose of this study was to analyze the citation characteristics of the top 100 most-cited articles published in dentistry with author(s) affiliated with Taiwan institutes.

Methods: The Scopus database was used to search the qualified articles with authors from Taiwan published in journals. The bibliometric parameters, including year of publication, study design, research fields, citation half-life, self-citation, institute of origin, and international collaboration were analyzed. Multivariable linear regression in generalized linear model was used to find associate factors related to trends of citation counts.

Results: The top 100 most-cited articles were determined by analyzing 7667 articles from the Scopus database. The steadily increasing trends were observed in the number and percentage of articles of author(s) affiliated with Taiwan institutes to the world. The most common study design was the in vitro research (55 %). The majority citation half-life is 3-5 and 6-8 years, and self-citation counts were between one to five times (n = 26). The percentage of international collaboration of these most-cited articles was 32%, and the main collaboration country was the United States. By using multivariable linear regression in the generalized linear model, the associated factors, study design, and self-citation were significantly associated with the escalating trends of citation counts.

Conclusion: This is the first study that provides valuable information in the dentistry regarding the academic activity, and empirical contribution of author(s) affiliated with Taiwan institutes in the world. The trends of citation characteristics were significantly correlated with study design and self-citation of these articles.
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http://dx.doi.org/10.1097/JCMA.0000000000000573DOI Listing
August 2021

Long-term maxillary anteroposterior changes following maxillary protraction with or without expansion: A meta-analysis and meta-regression.

PLoS One 2021 22;16(2):e0247027. Epub 2021 Feb 22.

Graduate Institute of Craniofacial and Dental Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Background: Maxillary protraction with or without expansion is a widely known orthopedic treatment modality in growing skeletal Class III patients. However, limited data are available regarding the outcomes of long-term changes in the maxilla. Aim of this meta-analysis was to assess the effectiveness of the long-term maxillary anteroposterior changes following a facemask therapy with or without rapid maxillary expansion in growing skeletal Class III patients.

Methods: A comprehensive literature search was conducted using the databases of PubMed, Science Direct, Web of Science, and Embase. Randomized controlled trials and cohort studies, published up to Sep. 2020, with maxillary protraction and/or expansion as keywords were included in this meta-analysis. Risk of bias within and across studies were assessed using the Cochrane tools (RoB2.0 and ROBINS-I) and GRADE approach. Overall and subgroup comparisons with the random-effect model were performed in this meta-analysis. Meta-regression models were designed to determine potential heterogeneity.

Results: There was a statistically significant increase (Mean difference, 2.29°; 95% confidence interval, 1.86-2.73; and p < 0.001 after facemask (FM) protraction. Mean difference, 1.73°; 95% confidence interval, 1.36-2.11; and p < 0.001 after rapid maxillary expansion(RME) and facemask protraction) in the Sella-Nasion-A point (SNA) angle in the treatment groups as compared with the control groups, when measured during the less than 3-year follow-up period. However, no statistically significant changes (Mean difference, 0.28°; 95% confidence interval, -0.57-1.13; and p = 0.52 after facemask protraction. Mean difference, 0.34°; 95% confidence interval, -0.64-1.33; and p = 0.50 after rapid maxillary expansion and facemask protraction) were observed in the SNA angle in the groups, when measured after 3 years of follow-up. Meta-regression analysis also showed that with increased follow-up duration, the effectiveness of maxillary protraction decreased.

Conclusion: This meta-analysis revealed that maxillary protraction therapy could be effective for a short-term in correcting maxillary hypoplasia and the treatment result was not affected by mean age and sex. However, with increased follow-up duration, the sagittal maxillary changes gradually decreased. Limitations on this review were only the SNA angle was used and clinical heterogeneity was not discussed. The quality of evidence was moderate. Further long-term observational studies are necessary for a comprehensive evaluation of the effects on maxillary skeletal changes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247027PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899359PMC
August 2021

Long-term maxillary three dimensional changes following maxillary protraction with or without expansion: A systematic review and meta-analysis.

J Dent Sci 2021 Jan 2;16(1):168-177. Epub 2020 Jul 2.

Graduate Institute of Craniofacial and Dental Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Background/purpose: Maxillary protraction with or without expansion appears to be an effective orthopedic treatment in skeletal class III growing patients, but the long-term effect on maxilla changes is less clear. The aim of this meta-analysis was to evaluate long-term three dimensional skeletal effects on maxilla through face mask (FM) with or without rapid maxillary expansion (RME) in skeletal CIII growing patients.

Materials And Methods: We searched database including PubMed, Science Direct, Embase and Web of Science through Feb 2020. Inclusion criteria were randomized controlled trials or cohort studies recruiting growing patients who received maxillary protraction and/or expansion and comparing the treatment groups with untreated controls. The follow-up periods were more than 3 years. Risk of bias was assessed using the Cochrane tools (RoB2.0 and ROBINS-I). GRADE was used to qualify the evidence.

Results: This meta-analysis included 6 studies comprising 327 participants in total. No statistically significant changes were observed on the degree of Sella-Nasion-A point (SNA) in the treated groups when compared with the untreated controls. However, significant increase on maxillary rotation degree (mean difference: 8.20, 95% CI = 6.87-9.53,  < 0.001) and maxillary base width (mean difference: 2.27, 95% CI = 1.39-3.15,  < 0.001) in the treated groups, if compared with untreated controls.

Conclusion: Our results indicated that FM and FM/RME treatments might not be long-term effective on correcting maxillary anteroposterior hypoplasia in growing patients. Additionally, more long-term studies are still necessary to further assess its skeletal benefits on maxilla in vertical and transverse dimension.
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http://dx.doi.org/10.1016/j.jds.2020.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770293PMC
January 2021

Citation Characteristics of H-Classics Articles in Implant Dentistry: A Citation Analysis Using H-Classics Method.

Int J Oral Maxillofac Implants 2020 Sep/Oct;35(5):900-909

Purpose: Citation-based metrics, such as the H-classics method, have been used as an indicator to assess academic performance in the scientific community. However, information addressing issues regarding self-citation, citation half-life, and subject area of origin in implant dentistry is lacking. The purpose of this study was to investigate the citation characteristics of H-classics articles in implant dentistry throughout different time periods.

Materials And Methods: H-classics implant dentistry articles were searched and selected by applying the H-classics method from the Scopus database. Bibliometric analysis was conducted to evaluate the citation characteristics, including institutional and journal self-citation, citation half-life, and subject area of origin of identified H-classics articles.

Results: The International Journal of Oral & Maxillofacial Implants and Clinical Oral Implants Research are the leading journals contributing the majority of citations to the retrieved H-classics articles. Articles published in the United States cited the most H-classics articles. Journal self-citation was 12.41% on average, while institutional self-citation was approximately 7.81%. Citation half-life decreased significantly across time periods, with an average decreasing ratio of 43.95%. Research on Scope III, bioengineering interventions, had the most prominent distribution citation frequency in the subject area "Others."

Conclusion: This study provides insightful views regarding citation characteristics of H-classics articles in implant dentistry (eg, interdisciplinary publications on bioengineering interventions) during the investigation periods, which may foster the translation of preclinical research into clinical applications in the future.
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http://dx.doi.org/10.11607/jomi.8129DOI Listing
October 2020

Growth arrest-specific 6 modulates adiponectin expression and insulin resistance in adipose tissue.

J Diabetes Investig 2021 Apr 13;12(4):485-492. Epub 2020 Oct 13.

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan.

Aims/introduction: Obesity is characterized by disturbed adipocytokine expression and insulin resistance in adipocytes. Growth arrest-specific 6 (GAS6) is a gene encoding the Gas6 protein, which is expressed in fibroblasts, and its related signaling might be associated with adipose tissue inflammation, glucose intolerance and insulin resistance. The aim of this study was to investigate the associations among Gas6, adipocytokines and insulin resistance in adipocytes.

Materials And Methods: Mature Simpson Golabi Behmel Syndrome adipocytes were treated with high levels of insulin to mimic insulin resistance, and were examined for the expressions of Gas6, cytokines and adipocytokines from preadipocytes in differentiation. In an animal study, high-fat diet-induced obese mice were used to verify the Gas6 expression in vitro.

Results: During the differentiation of adipocytes, the expression of Gas6 gradually decreased, and was obviously downregulated with adipocyte inflammation and insulin resistance. Gas6 levels were found to be in proportion to the expression of adiponectin, which has been regarded as closely relevant to improved insulin sensitivity after metformin treatment. Similar results were also confirmed in the animal study.

Conclusions: Our results suggest that Gas6 might modulate the expression of adiponectin, and might therefore be associated with insulin resistance in adipose tissues.
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http://dx.doi.org/10.1111/jdi.13412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015836PMC
April 2021

MiR-944/CISH mediated inflammation via STAT3 is involved in oral cancer malignance by cigarette smoking.

Neoplasia 2020 11 19;22(11):554-565. Epub 2020 Sep 19.

National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan; Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11696, Taiwan; Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. Electronic address:

The cytokine-inducible Src homology 2-containing protein (CISH) is an endogenous suppressors of signal transduction and activator of transcription (STAT) and acts as a key negative regulator of inflammatory cytokine responses. Downregulation of CISH has been reported to associate with increased activation of STAT and enhanced inflammatory pathways. However, whether microRNAs (miRNAs) play a crucial role in CISH/STAT regulation in oral squamous cell carcinoma (OSCC) remains unknown. The expression of CISH on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-944 and CISH were accessed by transwell migration and invasion analyses using gain- and loss-of-function approaches. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were used to evaluate the pro-inflammation cytokines expression under the miR-944, CISH, NNK or combinations treatment. We found that the CISH protein, which modulates STAT3 activity, as a direct target of miR-944. CISH protein was significantly down-regulated in OSCC patients and cell lines and its level was inversely correlated with miR-944 expression. The miR-944-induced STAT3 phosphorylation, pro-inflammation cytokines secretion, migration and invasion were abolished by CISH restoration, suggesting that the oncogenic activity of miR-944 is CISH dependent. Furthermore, tobacco extract (NNK) may contribute to miR-944 induction and STAT3 activation. Antagomir-mediated inactivation of miR-944 prevented the NNK-induced STAT3 phosphorylation and pro-inflammation cytokines secretion. Altogether, these data demonstrate that NNK-induced miR944 expression plays an important role in CISH/STAT3-mediated inflammatory response and activation of tumor malignancy.
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http://dx.doi.org/10.1016/j.neo.2020.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505767PMC
November 2020

Association between the presence of distolingual root in mandibular first molars and the presence of C-shaped mandibular second molars: a CBCT study in a Taiwanese population.

Quintessence Int 2020 ;51(10):798-807

Objectives: The purpose of this study was to assess the prevalence of C-shaped canals in permanent mandibular second molars (SMs) and to determine whether its appearance was associated with the presence of distolingual root (DLR) in permanent mandibular first molars (FMs).

Method And Materials: Three hundred and eighty patients were qualified for evaluation of their FMs and SMs using cone beam computed tomography. The prevalence, distribution pattern, external root morphology, and the internal root canal anatomy of the examined molars were recorded and analyzed. Furthermore, the association between the root canal configurations of SMs and the appearance of DLR in FMs was also assessed.

Results: The prevalence of SMs with C-shaped root canals was 44.7%. The most common root canal configuration type of the one-rooted SMs with C-shaped anatomy was C3 (45.6%), followed by C2 and C1. The frequency of C-shaped canals in SMs was 45.4% in Non-DLR group, 52.8% in unilateral DLR group, and 33.9% in bilateral DLR group, respectively. Moreover, the prevalence of C-shaped root canals in SMs with the presence of bilateral DLRs in FMs was significantly lowered.

Conclusion: The association between the presence of DLR in FMs and C-shaped canal configurations in neighboring SMs was surveyed, and the prevalence of C-shaped root canals in SMs with the presence of bilateral DLRs in FMs was found to be significantly lowered.
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http://dx.doi.org/10.3290/j.qi.a45266DOI Listing
October 2020

Correction to: Gamma synuclein is a novel nicotine responsive protein in oral cancer malignancy.

Cancer Cell Int 2020 26;20:410. Epub 2020 Aug 26.

Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, No. 161, Sec. 6, Min‑Chuan East Rd., Nei‑Hu, Taipei, 114 Taiwan.

[This corrects the article DOI: 10.1186/s12935-020-01401-w.].
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http://dx.doi.org/10.1186/s12935-020-01478-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448332PMC
August 2020

Innovation of dental education during COVID-19 pandemic.

J Dent Sci 2021 Jan 19;16(1):15-20. Epub 2020 Aug 19.

School of Dentistry, National Yang-Ming University, Taipei, Taiwan.

Background/purpose: The impact of the pandemic of COVID-19 has a certain influence on various walks of life around the world. Because of the pandemic of this novel coronavirus in terms of COVID-19, the social life global wide has been changed a lot. To keep the social distance between human being to prevent from being infected is the most important strategy for all the countries. Many dental schools have been locked down to minimize the spread out of this coronavirus infection. Close contact between human being are required for all those learning process in traditional dental education. Learning methods should be innovated to keep on the learning process but away from being infected for dental education during pandemic. The purpose of this manuscript is to exchange the information and experience of those dental educators from different countries to prepare for the future demand for dental education during pandemic.

Materials And Methods: By means of three online symposiums, dental educators from different countries were invited to give presentation and discussion regarding to the information and experience in the innovation of dental education during the pandemic.

Results: The results showed that the impact of the pandemic of COVID-19 affects the dental education a lot. Intelligent technology has certain benefit for the learning process of dental education during the pandemic.

Conclusion: The impact of the pandemic of COVID-19 affects dental education a lot. The model of dental education should be innovated to suit different situations and novelty intelligent technology should be applied for future dental education.
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http://dx.doi.org/10.1016/j.jds.2020.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437532PMC
January 2021

Osteoporosis and the risk of temporomandibular disorder in chronic obstructive pulmonary disease.

J Bone Miner Metab 2021 Mar 28;39(2):201-211. Epub 2020 Jul 28.

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.

Introduction: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide. The coexistence of COPD and temporomandibular disorder (TMD) has been noted, and dysfunctional mastication resulting from TMD can worsen individuals' nutritional status. This association between COPD and TMD has been rarely discussed in previous studies. Therefore, this study aimed to determine whether osteoporosis increases the risk of TMD in COPD and whether anti-osteoporosis medications can prevent TMD.

Materials And Methods: This retrospective nationwide population-based study utilized the Taiwan National Health Insurance Research Database. We enrolled 52,652 COPD patients between 2000 and 2015: 13,163 with osteoporosis and 39,489 without osteoporosis. Groups of COPD patients with and without osteoporosis were age- and sex-matched. A multivariable Cox proportional hazards regression model was used to evaluate the risk of TMD development in COPD patients with and without osteoporosis over 15 years.

Results: There was a higher risk of TMD occurrence in COPD patients with osteoporosis than in those without osteoporosis (adjusted hazard ratio 2.564, P < 0.001) after adjusting for demographic variables and associative comorbidities. Osteoporosis, hypertension, vertebral compression fracture, and nonpsychotic mental disorders were risk factors contributing to TMD development in patients with COPD. Anti-osteoporosis medications were associated with the prevention of TMD development concomitant with osteoporosis and COPD (adjusted hazard ratio 0.617, P = 0.004).

Conclusions: Patients with COPD and osteoporosis are at a higher risk of developing TMD, and anti-osteoporosis medications can prevent the development of TMD in this context.
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http://dx.doi.org/10.1007/s00774-020-01134-wDOI Listing
March 2021

Gamma synuclein is a novel nicotine responsive protein in oral cancer malignancy.

Cancer Cell Int 2020 10;20:300. Epub 2020 Jul 10.

Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, No.161, Sec.6, Min-Chuan East Rd., Nei-Hu, Taipei, 114 Taiwan.

Background: The mechanisms of neuronal protein γ-synuclein (SNCG) in the malignancy of oral squamous cell carcinoma (OSCC) are not clear. This study tested the hypothesis that SNCG is involved in nicotine-induced malignant behaviors of OSCC. The effect of nicotine on SNCG expression and epithelial-to-mesenchymal transition (EMT) markers were examined.

Methods: Short hairpin RNA (shRNA) and an antagonist specific for α7-nicotine acetylcholine receptors (α7-nAChRs) were used to examine the role of α7-nAChRs in mediating the effects of nicotine. Knockdown of SNCG in nicotine-treated cells was performed to investigate the role of SNCG in cancer malignancy. The in vivo effect of nicotine was examined using a nude mouse xenotransplantation model.

Results: Nicotine increased SNCG expression in a time- and dose-dependent manner. Nicotine treatment also increased E-cadherin and ZO-1 and decreased fibronectin and vimentin expression. After specific knockdown of α7-nAChRs and inhibition of the PI3/AKT signal, the effect of nicotine on SNCG expression was attenuated. Silencing of SNCG abolished nicotine-induced invasion and migration of OSCC cells. The xenotransplantation model revealed that nicotine augmented tumor growth and SNCG expression.

Conclusion: Nicotine upregulated SNCG expression by activating the α7-nAChRs/PI3/AKT signaling that are participated in nicotine-induced oral cancer malignancy.
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http://dx.doi.org/10.1186/s12935-020-01401-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350738PMC
July 2020

The prognostic factors of recurrence and survival in female patients with lung adenocarcinoma and breast cancer.

J Cancer Res Clin Oncol 2020 May 27;146(5):1299-1306. Epub 2020 Feb 27.

Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan, ROC.

Background: The aim of this study was to verify the predictors of recurrence and survival in lung adenocarcinoma patients with experiences of breast cancer therapies.

Methods: We retrospectively reviewed consecutive patients who were treated at our hospital for lung adenocarcinoma from 2004/01 to 2014/03. The patients were divided into groups of those with lung adenocarcinoma alone and those with lung and breast cancer. Kaplan-Meier plots and log-rank tests were used to estimate outcomes.

Results: 54 patients with lung adenocarcinoma and breast cancer were compared with 457 patients with single primary lung adenocarcinomas. After propensity score matching with control of age, operation type, smoking status and pathologic stage, tumor differentiation, recurrence rate and tumor size were significantly different between two groups. The significant predictors for recurrence included undergone chemotherapy (HR = 25, p < 0.001), moderate/poor differentiation (HR = 8.125, p = 0.012), tumor size ≧ 2 cm (HR = 15, p < 0.001), LVSI (HR = 13.67, p = 0.031) and GGO ratio < 50% (HR = 14.667, p = 0.014). The significant prognostic factors for survival were accepted chemotherapy (HR = 6.182, p = 0.021), LVSI (HR = 22, p = 0.012) and GGO ratio < 50% (HR = 9.143, p = 0.045). Kaplan-Meier analysis revealed that patients with lung adenocarcinoma and breast cancer had a better 5-year disease-free survival (p = 0.009), while the Her2-negative patients obtained a better overall survival (p = 0.038).

Conclusions: In patients with breast cancer and lung adenocarcinoma, independent risk factors of recurrence were undergone chemotherapy, moderate/poor differentiation, tumor size ≧ 2 cm, LVSI and GGO ratio < 50%. Only undergone chemotherapy, LVSI and GGO ratio < 50% were significant poor predictors for survival. However, patients with metachronous lung adenocarcinoma and breast cancer had better disease-free survival and less tumor recurrence than patients with lung adenocarcinoma alone.
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http://dx.doi.org/10.1007/s00432-020-03162-5DOI Listing
May 2020

The prevalence of first-onset temporomandibular disorder in low back pain and associated risk factors: A nationwide population-based cohort study with a 15-year follow-up.

Medicine (Baltimore) 2020 Jan;99(3):e18686

Graduate Institute of Medical Sciences.

The coexistence of low back pain (LBP) and temporomandibular disorder (TMD) has often been noted clinically. However, studies of the association between these two conditions involving a large population with longitudinal evidences are lacking. Therefore, the study aimed to investigate the association between LBP and TMD in a nationwide-matched cohort population with a 15-year follow-up.Data of 65,121 patients newly diagnosed with LBP were analyzed, along with those of 195,363 (1:3) sex- and age-matched controls. Multivariate Cox regression analysis was used to determine TMD risk between the LBP and non-LBP groups. Kaplan-Meier method was used for determining the cumulative risk of first-onset TMD between groups, with a 15-year follow-up.The LBP group was more likely to develop first-onset TMD (adjusted hazards ratio (HR) = 1.561, P < .001), after adjusting for demographic variables and comorbidities. The risk factors for TMD were LBP, young age, higher insured premium, and osteoporosis. In the subgroup analysis, the LBP group had a higher risk of TMD than the non-LBP group in all stratifications.LBP is the risk factor contributing to the development of first-onset TMD. Therefore, clinicians should be reminded to manage LBP disorders concurrently when treating TMD.
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http://dx.doi.org/10.1097/MD.0000000000018686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220485PMC
January 2020

α7-Nicotine acetylcholine receptor mediated nicotine induced cell survival and cisplatin resistance in oral cancer.

Arch Oral Biol 2020 Mar 8;111:104653. Epub 2020 Jan 8.

Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan. Electronic address:

Objective: To investigate the effect of nicotine on cell survival and cisplatin resistance in oral cancer and the possible involvement of α7-nicotinic acetylcholine receptors (α7-nAChRs).

Design: The effects of nicotine on cell survival and cisplatin-induced apoptosis were assessed. Knockdown of α7-nAChRs by short hairpin RNA and the specific antagonist methyllycaconitine (MLA) was used to examine the involvement of α7-nAChRs in modulating the effects of nicotine. Apoptosis signal molecules were examined in nicotine- and cisplatin-treated cells.

Results: Nicotine increased the survival of the oral cancer cells YD8 and OEC-M1 in a dose- and time-dependent manner. Nicotine treatment accelerated cell cycle progression in the oral cancer cells, and significantly reduced cisplatin-induced cell apoptosis. In the α7-nAChR-silenced cells, the prosurvival effect of nicotine in the cisplatin-treated cells was attenuated. Co-treatment of cisplatin and nicotine attenuated the effect of cisplatin on Bcl-2 expression. In addition, the effect of nicotine on cell survival under cisplatin treatment was attenuated with the addition of the Bcl-2 inhibitor ABT-737.

Conclusions: Treating oral cancer cells with nicotine increased cell survival and cisplatin resistance, in which α7-nAChRs were involved.
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http://dx.doi.org/10.1016/j.archoralbio.2020.104653DOI Listing
March 2020

Macrophage phenotypes and Gas6/Axl signaling in apical lesions.

J Dent Sci 2019 Sep 4;14(3):281-287. Epub 2019 Apr 4.

Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Background/purpose: Macrophages participate in the periapical inflammation with pro-inflammatory M1 cells and anti-inflammatory M2 cells. Gas6/Axl signal is the responsible pathway for the activation of M1 and polarization of M2. The aim of this study was to compare the number of CD16 M1 cells, CD206 M2 cells, and Gas6/Axl expression between apical granulomas and radicular cysts.

Materials And Methods: Twenty-four cases of granuloma and twenty of cysts were submitted to immunohistochemistry using anti-CD16 and anti-CD206 antibodies for determining M1 and M2 macrophages and investigating the cells with positive Gas6 and Axl expression.

Results: There were more numerous of M1 macrophages in radicular cysts (175.9 ± 87.7) compared to apical granuloma (116.6 ± 55.8), and M2 macrophages was higher in cysts (204.0 ± 97.6) than granuloma (152.9 ± 64.6). The level of Gas6/Axl expression were similar. There was a significant different in M1 macrophage (P = 0.014) between two diagnosis. In patients with or without root resorption, the number of M1 were 194.6 ± 57.2 compared with 139.1 ± 79.6. The number of M2 were 241.7 ± 81.4 and 164.6 ± 77.1. The expression of Axl was stronger in root resorption patients (191.1 ± 43.6), but the tendency in Gas6 expression was similar. Significant differences were noted in high M2 infiltration and Axl positive lesions.

Conclusion: It appears that macrophages associated with significantly higher numbers in radicular cysts than apical granuloma. Meanwhile, macrophages and Axl receptor was intensively expressed in patients with root resorption, related to severe inflammation.
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http://dx.doi.org/10.1016/j.jds.2018.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739459PMC
September 2019

Chronic obstructive pulmonary disease combined with vertebral compression fracture increases the risk of temporomandibular disorder: A population-based cohort study.

Medicine (Baltimore) 2019 Sep;98(37):e17162

Graduate Institute of Medical Sciences.

Vertebral compression fracture (VCF) is a common comorbidity of chronic obstructive pulmonary disease (COPD), and the coexistence of COPD and temporomandibular disorder (TMD) has been clinically noted. The present study aimed to investigate whether VCF increases the risk of TMD in patients with COPD.With a follow-up period of 15 years, this retrospective, population-based longitudinal cohort study enrolled sex- and age-matched COPD patients with and without VCF (1:3) who were identified from Taiwan's National Health Insurance Research Database from 2000 to 2015. Multivariate Cox regression analysis was performed to determine the risk of TMD in COPD patients with and without VCF. The cumulative risk of TMD between groups was estimated using Kaplan-Meier analysis.The risk factors for TMD in patients with COPD were VCF, osteoporosis, and winter season. The COPD with VCF group was more likely to develop TMD (adjusted hazard ratio = 3.011, P < .001) than the COPD without VCF group after adjustment for sex, age, variables, and comorbidities. In the subgroup analysis, the COPD with VCF group had a higher risk of TMD than the COPD without VCF group in almost all stratifications.COPD patients with VCF are at a higher risk of developing TMD. Clinicians taking care of patients with COPD should be aware of the occurrence of TMD as a comorbidity.
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http://dx.doi.org/10.1097/MD.0000000000017162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750274PMC
September 2019

Cilostazol inhibits hyperglucose-induced vascular smooth muscle cell dysfunction by modulating the RAGE/ERK/NF-κB signaling pathways.

J Biomed Sci 2019 Sep 6;26(1):68. Epub 2019 Sep 6.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Background: Increasing evidence suggests that high glucose (HG) causes abnormalities in endothelial and vascular smooth muscle cell function (VSMC) and contributes to atherosclerosis. Receptor for advanced glycation end-products (RAGE) has been linked to the pathogenesis of both the macrovascular and microvascular complications of diabetes. Cilostazol is used to treat diabetic vasculopathy by ameliorating HG-induced vascular dysfunction.

Objectives: In this study, we investigated whether the cilostazol suppression of HG-induced VSMC dysfunction is through RAGE signaling and its possible regulation mechanism.

Method: We investigated the effect of HG and cilostazol on RAGE signaling in A7r5 rat VSMCs. Aortic tissues of streptozotocin (STZ) diabetic mice were also collected.

Results: Aortic tissue samples from the diabetic mice exhibited a significantly decreased RAGE expression after cilostazol treatment. HG increased RAGE, focal adhesion kinase (FAK), matrix metalloproteinase-2 (MMP-2), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions, and was accompanied with increased reactive oxygen species (ROS), cell proliferation, adhesion and migration. Cilostazol significantly reversed HG-induced RAGE, ROS, downstream gene expressions and cell functions. RAGE knockdown significantly reversed the expressions of HG-induced vasculopathy related gene expressions and cell functions. Cilostazol with RAGE knockdown had additive effects on downstream ERK/NF-κB signaling pathways, gene expressions and cell functions of A7r5 rat VSMCs in HG culture.

Conclusions: Both in vitro and in vivo experimental diabetes models showed novel signal transduction of cilostazol-mediated protection against HG-related VSMC dysfunction, and highlighted the involvement of RAGE signaling and downstream pathways.
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http://dx.doi.org/10.1186/s12929-019-0550-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731603PMC
September 2019

The prevalence and distribution of radiopaque, calcified pulp stones: A cone-beam computed tomography study in a northern Taiwanese population.

J Dent Sci 2018 Jun 10;13(2):138-144. Epub 2017 Nov 10.

School of Dentistry, Tri-Service General Hospital and National Defense Medical Center, Taipei 11490, Taiwan.

Background/purpose: Presence of pulp stones increase the difficulty of locating canal orifice during endodontic treatment. This study aims to determine the prevalence of pulp stones in a northern Taiwanese population through analysis of cone beam computed tomography (CBCT).

Materials And Methods: A total of 144 patients and 2554 teeth were used in the present study which were collected from a CBCT image archive. To determine the presence of pulp stones, images of pulp chamber and root canals were analyzed in the sagittal, axial and coronal planes and from the occlusal to apical direction. Correlations between pulp stones and gender, age, tooth type, dental arch or side were also examined.

Results: Of the 144 patients, 120 patients (83.3%) and 800 (31.3%) teeth were found to have one or more pulp stones through CBCT examination. Prevalence of pulp stones between dental arches and tooth types were significantly different ( < 0.001). Pulp stones were found to be the most prevalent in first molars (50.0%) and most scarce in first premolars (18.8%). There was no significant correlation between pulp stones and gender, increasing age, or dental sides.

Conclusion: Pulp stones are more frequent in maxillary teeth compared to mandibular teeth. Pulp stones in molar teeth were significantly more common than premolars and incisors. CBCT could be a sensitive tool to detect pulp stones, especially simplifying identification of pulp stones in radicular pulp. Knowledge of pulp stones distribution can aid dentists in clinical endodontic treatment.
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http://dx.doi.org/10.1016/j.jds.2017.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388828PMC
June 2018

Detection and location of second mesiobuccal canal in permanent maxillary teeth: A cone-beam computed tomography analysis in a Taiwanese population.

Arch Oral Biol 2019 Feb 12;98:108-114. Epub 2018 Nov 12.

School of Dentistry, Tri-Service General Hospital and National Defense Medical Center, Taipei, 11490, Taiwan. Electronic address:

Objectives: The aim of this study was to analyze the incidence, symmetry, concurrence of second mesiobuccal canal (MB2) and determine geometric relationships between each orifice of maxillary first and second molars by cone-beam computed tomography (CBCT) analysis.

Methods: A total of 216 qualified individuals' (503 teeth) CBCT image were enrolled in the present study. The consistency of bilateral symmetry and concurrent appearance of MB2 canals were analyzed among individuals with contralateral and adjacent molar teeth. The inter-orifice distances and angulations of first and second molars were also measured.

Results: The overall incidence of MB2 canal of maxillary molars was 39.2%, in which 45.9% and 32.3% in the first and second molars, respectively. The distribution of MB2 canal in contralateral molar teeth has significant gender difference in second molars (p = 0.024) while analyzing the frequency of MB2 canal appearing in contralateral molar pairs. The simultaneous occurrence of MB2 canal was 22.4% for contralateral molars, and the prevalence of concurrent appearance of MB2 canal in the adjacent molars was 43.4%. After adjusting for gender, age, and tooth type, the inter-orifice distances of mesiobuccal to palatal (odds ratios = 1.891) and to distobuccal (odds ratios = 1.448) canals, demonstrated significant differences between molars with and without MB2 canals.

Conclusions: The clinical significance of the results presents critical information on the geometric features, including inter-orifice distances and angulations between each orifice in maxillary molar teeth. Further studies should be conducted to investigate the exact anatomic coordination between each orifice and its impact on access preparation and external crown morphology.
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http://dx.doi.org/10.1016/j.archoralbio.2018.11.006DOI Listing
February 2019

Plasma Growth Arrest-Specific 6 Protein and Genetic Variations in the GAS6 Gene in Patients with Metabolic Syndrome.

Metab Syndr Relat Disord 2019 02 20;17(1):22-28. Epub 2018 Oct 20.

1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Background: Growth arrest-specific 6 (Gas6) is a vitamin K-dependent protein secreted by immune cells, endothelial cells, vascular smooth muscle cells, and adipocytes. Recent studies indicate that Gas6 and receptors of the TAM (Tyro3, Axl, and Mer) family may be involved in the pathogenesis of obesity, systemic inflammation, and insulin resistance. The aim of this study was to investigate the association between plasma Gas6 protein and the c.843 + 7G>A Gas6 polymorphism in metabolic syndrome (MetS).

Methods: Two hundred five adults (88 men and 117 women) were recruited in this study. Plasma Gas6 concentration, general, and biochemical data were measured. All subjects were genotyped for the c.843 + 7G>A Gas6 polymorphism.

Results: Plasma Gas6 concentrations decreased in parallel with various MetS components in all groups (P = 0.017 for trend). Patients in the second and third tertiles of Gas6 level had higher high-density lipoprotein cholesterol (HDL-C) levels than those in the first tertile overall and in the female group. Plasma Gas6 levels were significantly positively correlated with HDL-C level and negatively with fasting glucose level in the female patients. The A allele and genotype AA in single nucleotide polymorphism c.843 + 7G>A were less frequent in the subjects with MetS compared to those without MetS.

Conclusions: Our results demonstrated a positive correlation between Gas6 protein values and HDL-C and reinforce the association with fasting glucose. In addition, the presence of c.843 + 7G>A Gas6 polymorphisms, especially the AA genotype, had an association with MetS. The potential role of the Gas6/TAM system in MetS deserves further investigation.
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http://dx.doi.org/10.1089/met.2017.0143DOI Listing
February 2019

OCT4B mediates hypoxia-induced cancer dissemination.

Oncogene 2019 02 12;38(7):1093-1105. Epub 2018 Sep 12.

Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan.

Hypoxia, the reduction of oxygen levels in cells or tissues, elicits a set of genes to adjust physiological and pathological demands during normal development and cancer progression. OCT4, a homeobox transcription factor, is essential for self-renewal of embryonic stem cells, but little is known about the role of OCT4 in non-germ-cell tumorigenesis. Here, we report that hypoxia stimulates a short isoform of OCT4, called OCT4B, via a HIF2α-dependent pathway to induce the epithelial-mesenchymal transition (EMT) and facilitate cancer dissemination. OCT4B overexpression decreased epithelial barrier properties, which led to an increase in cell migration and invasion in lung cancer cells. OCT4B knockdown attenuated HIF2α-induced EMT and inhibited cancer dissemination in cell-line and animal models. We observed that OCT4B bound the SLUG promoter and enhanced its expression, and SLUG silencing inhibited OCT4B-mediated EMT, accompanied with decreased cell migration and invasion. Correlation analysis revealed that OCT4B expression was significantly associated with the SLUG level in lung tumors. These results provide novel insights into OCT4B-mediated oncogenesis in cancer dissemination.
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http://dx.doi.org/10.1038/s41388-018-0487-6DOI Listing
February 2019

Axl Involved in Mineral Trioxide Aggregate Induces Macrophage Polarization.

J Endod 2018 Oct 28;44(10):1542-1548. Epub 2018 Aug 28.

Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. Electronic address:

Introduction: In this study, we examined the effect of mineral trioxide aggregate (MTA) on macrophage polarization and the potential involvement of Axl/nuclear factor kappa B (NF-κB) signaling in mediating the effect of MTA.

Methods: The human monocyte cell line THP-1 was cultured with MTA solution for 1, 2, or 3 days, and the population change of M2 macrophages was analyzed by flow cytometry. Expression of M2 cytokines was examined by enzyme-linked immunosorbent assay. Phagocytosis and angiogenesis-induction ability were also assayed. The involvement of Axl/NF-κB signaling in MTA-treated cells was examined by analyzing phosphorylation status of Axl, Akt, IKKα/β, and IκBα. Specific inhibitors for Axl/Akt/NF-κB signaling were added to MTA-treated THP-1 cells, and their cytokine expression change was examined.

Results: Flow cytometry analysis showed that MTA treatment increased CD206+ cells in a time-dependent way. After MTA treatment, the expression of M2-related cytokines was up-regulated. MTA also enhanced phagocytic ability and the ability of THP-1 cells to induce angiogenesis. Treatment of MTA led to activate Axl/Akt/NF-kB signal axis by phosphorylation of Axl, Akt, IKKα/β, IκBα, and p65. In addition, MTA-induced interleukin 10, transforming growth factor beta, and vascular endothelial growth factor expression was suppressed as specific inhibitors were added.

Conclusions: Our findings indicate that MTA is able to induce macrophage polarization toward the M2 phenotype, with up-regulation of interleukin 10, transforming growth factor beta, and vascular endothelial growth factor, and that Axl/Akt/NF-κB signaling participates in this process. These results provide the cellular and molecular basis of MTA's anti-inflammatory action in clinical applications.
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http://dx.doi.org/10.1016/j.joen.2018.07.005DOI Listing
October 2018

Relationship of the Incidence of C-shaped Root Canal Configurations of Mandibular First Premolars with Distolingual Roots in Mandibular First Molars in a Taiwanese Population: A Cone-beam Computed Tomographic Study.

J Endod 2018 Oct 23;44(10):1492-1499.e1. Epub 2018 Aug 23.

School of Dentistry, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan. Electronic address:

Introduction: The aim of this study was to determine the prevalence of C-shaped canal configurations (CSs) and radicular grooves (RGs) in permanent mandibular first premolars (MPs) and to investigate the relevance of such complexities with the presence of distolingual roots (DLRs) in permanent mandibular first molars (MMs).

Methods: A total of 800 pairs of MPs and MMs were investigated using a cone-beam computed tomographic system (NewTom 5G; QR srl, Verona, Italy). The frequency and symmetry of DLRs in MMs along with the occurrence of RGs and CSs in examined MPs were evaluated. Multivariable logistic regression analysis was applied to examine the correlation between the CSs of MPs with the appearance of DLRs in MMs.

Results: In the examined teeth, 23.0% of MMs had a DLR, whereas 16.6% of MPs had RGs and 12.5% of MPs had C-shaped canals. Although the most common canal configuration in MPs is the single canal (74.1%), the other 25.9% still possess complicated root canals. Of these MPs that have different canal configurations, 54.6% had 2 canals, whereas 44.4% had CSs. Specifically, the CS showed a high prevalence of C3 morphologies at 98.9% followed by C1 at 1.1%. A corresponding and increasing frequency was noted in CSs and RGs of MPs and MMs with DLRs (P < .001). After adjusting for related categoric variables, the adjusted odds ratios for CSs of MPs in the bilateral DLR group compared with the non-DLR group was 3.294 (P < .001).

Conclusions: This study showed an increased appearance of CSs in MPs when DLRs were present in MMs in the Taiwanese population.
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http://dx.doi.org/10.1016/j.joen.2018.05.016DOI Listing
October 2018

Increasing prominence of implantology research: a chronological trend analysis of 100 top-cited articles in periodontal journals.

Eur J Oral Implantol 2018 ;11(1):97-110

Purpose: To identify 100 top-cited articles published in periodontal journals and analyse the research trends by using citation analysis.

Materials And Methods: 100 top-cited articles published in periodontal journals were retrieved by searching the database of the ISI Web of Science and Journal Citation reports. For each article, the following principal bibliometric parameters: authorship, geographic and institute origin, manuscript type, study design, scope of study, and citation count of each time period were analysed from 1965 to 2015.

Results: The identified 100 top-cited articles were retrieved from five periodontal journals and citation counts were recorded between 262 and 1,693 times. For the institute of origin, the most productive institute, in terms of the number of 100 top-cited articles published, was the University of Gothenburg (Sweden) (n = 19), followed by the Forsyth Dental Center (USA) (n = 15). Most manuscripts were original research (n = 74), and the inflammatory periodontal disease (n = 59) was the most frequent topic studied. Interestingly, the trend of increase average citation reached significance for implantology (β = 26.75, P = 0.003) and systemic interactions (β = 29.83, P = 0.005), but not for inflammatory disease (β = -10.30, P = 0.248) and tissue regeneration (β = 9.04, P = 0.081). By using multivariable linear regression in a generalised linear model, suitable published journal (Journal of Clinical Periodontology), geographic regions (Europe), more intense international collaboration, adequate manuscript type (review article) and study design (systematic review) could be attributed to escalating average citation counts in implantology (all P < 0.05). However, for systemic interactions, only geographic region and study design were significantly associated with the increasing citation trend.

Conclusions: These principal bibliometric characteristics revealed escalated trends in average citation count in implantology throughout time.
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May 2018

The Presence of Distolingual Root in Mandibular First Molars Is Correlated with Complicated Root Canal Morphology of Mandibular Central Incisors: A Cone-beam Computed Tomographic Study in a Taiwanese Population.

J Endod 2018 May 1;44(5):711-716.e1. Epub 2018 Mar 1.

Department of Periodontology, School of Dentistry, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan. Electronic address:

Introduction: The aim of this study was to assess the prevalence of complicated root canals in permanent mandibular central incisors (PMCIs) and its correlation with the presence of a distolingual root (DLR) in permanent mandibular first molars (PMFMs) using cone-beam computed tomographic imaging in a Taiwanese population.

Methods: A total of 400 patients (800 pairs of PMCIs and PMFMs) were qualified for further analysis. The prevalence of DLRs in PMFMs along with root canal configurations of PMCIs were assessed at subject and tooth levels. Multivariable logistic regression analysis was used to evaluate the correlation between the root canal configurations of PMCIs with the existence of DLRs in PMFMs.

Results: The prevalence of PMFMs with DLRs and complicated root canal configurations in PMCIs was 23.0% and 15.6%, respectively. A significant difference in age (<50 years vs ≥50 years) was found for complicated root canal configurations in PMCIs. The most prevalent root canal system in PMCIs was Vertucci type I (84.4%) followed by type III (13.5%). A positive correlation between the presence of DLRs in PMFMs and complicated root canal configurations in PMCIs was noted. After adjusting for categoric variables including sex, age, and side, the odds ratios for the occurrence of complicated root canal configurations of PMCIs in the unilateral DLR group and the bilateral DLR group compared with the non-DLR group were 2.13 and 2.53, respectively.

Conclusions: The concurrent appearance of DLRs in PMFMs and complicated root canal morphology in PMCIs is prominent in Taiwanese individuals.
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http://dx.doi.org/10.1016/j.joen.2018.01.005DOI Listing
May 2018

Periodontal status of tooth adjacent to implant with peri-implantitis.

J Dent 2018 03 8;70:104-109. Epub 2018 Jan 8.

Department of Dentistry, Tzu Chi General Hospital - Xindian Branch, New Taipei City, Taiwan, ROC.

Objectives: To evaluate the relationship between peri-implantitis and the periodontal health of the adjacent tooth, the periodontal status of the teeth adjacent and contralateral to the implants with and without peri-implantitis.

Methods: Fifty-three subjects with existing dental implants and chronic periodontitis were examined in this cross-sectional study. Seventy implants were categorized into peri-implantitis (n = 42) and healthy/mucositis (n = 28) groups. The periodontal and peri-implant status, including probing depth (PD), clinical attachment level (CAL), and gingival recession (GR) were measured at 6 sites around the implants and the teeth adjacent and contralateral to those implants. In total 560 sites of the 70 teeth/implant sets, the association between the periodontal status at the near and away sites of the teeth (according to implant) and the implant status (without/with peri-implantitis) was examined.

Results: A significantly different mean PD (5.01 ± 1.69, 4.42 ± 1.8, 3.55 ± 0.88, and 3.71 ± 1.07 mm, p < 0.001) and CAL (6.02 ± 2.36, 4.89 ± 2.04, 4.35 ± 1.11, and 4.35 ± 1.5 mm, p < 0.001) were noted at the near sites of the teeth adjacent to the implants with peri-implantitis when compared with the away sites of adjacent and contralateral teeth and the near sites of contralateral teeth. With generalized estimating equation (GEE), the presence of peri-implantitis (β  = 1.041 mm, confidence interval = 0.646-1.435, and p < 0.001; β  = 0.857 mm, confidence interval = 0.279-1.434, and p < 0.004) and tooth location (β  = 0.65 mm, confidence interval = 0.4-0.9, and p < 0.001; β  = 0.682 mm, confidence interval = 0.34-1.024, and p < 0.001) were significantly associated with the values of the PD and CAL of the teeth. Moreover, the factor of examining sites (i.e. near and away sites of the tooth) was significantly associated with CAL (β = 0.304 mm, confidence interval = 0.019-0.588, and p = 0.036) and GR (β = 0.136 mm, confidence interval = 0.02-0.252, and p = 0.022).

Conclusion: The existence of peri-implantitis, the tooth location, and the examining site are significantly associated with the periodontal measurements of the remaining teeth.

Clinical Significance: Peri-implant health is related to the periodontal health of the natural teeth close to the dental implant.
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http://dx.doi.org/10.1016/j.jdent.2018.01.004DOI Listing
March 2018

Estrogen modulates vascular smooth muscle cell function through downregulation of SIRT1.

Oncotarget 2017 Dec 10;8(66):110039-110051. Epub 2017 Nov 10.

Division of Cardiovascular Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Background: There are sex differences in the incidence and severity of cardiovascular disease. Although an estrogen-mediated vasculoprotective effect is widely accepted, clinical trial results have been conflicting and the detailed mechanisms are still unclear. Sirtuin 1 (SIRT1), a class III histone deacetylase, may protect against vascular aging and atherosclerosis; however, the effects of estrogen on SIRT1 expression and vascular smooth muscle cell (VSMC) behavior remain unknown.

Materials And Methods: We ovariectomized (OVX) female, wild-type, C57BL/6J mice, which were randomized into non-estrogen- and estrogen-supplemented groups. We also treated A7r5 VSMCs with 17-β-estradiol and resveratrol, a SIRT1 activator, , and measured the expression of SIRT1 and apoptotic markers, as well as proliferation, viability, and migration.

Results: Aortic tissue from OVX mice exhibited marked VSMC hyperplasia and upregulation of SIRT1, which was reversed by 17-β-estradiol supplementation, as assessed by western blotting and immunohistochemical staining. , 17-β-estradiol downregulated SIRT1 expression in a dose- and time-dependent manner, increased apoptosis, and reduced proliferation, viability, and migration. Resveratrol reversed these effects through the activation of SIRT1. Estrogen appeared to mediate its effects through the Akt and ERK pathways.

Conclusions: Estrogen may regulate cardiovascular health via the expression of SIRT1, possibly through the AKT and ERK signaling pathways.
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http://dx.doi.org/10.18632/oncotarget.22546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746363PMC
December 2017

The role of Thyroid Transcription Factor-1 and Tumor differentiation in Resected Lung Adenocarcinoma.

Sci Rep 2017 10 27;7(1):14222. Epub 2017 Oct 27.

Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Republic of China.

To investigate the role of thyroid transcription factor-1 (TTF-1) and tumor differentiation in resected lung adenocarcinoma. A total of 520 patients with clinical early stage lung adenocarcinoma who underwent surgical resection were reviewed retrospectively. Clinical data and outcomes were evaluated with an average follow-up of 117 months. The results were validated via lung cancer cell line studies. The clinical parameters did not differ between relapse and nonrelapse patients. Exceptions were tumor differentiation, lymphovascular space invasion, F-fluorodeoxyglucose maximum standard uptake value, tumor size, and pathological stage (p < 0.001). Poor tumor differentiation was the independent prognostic factor (odds ratio: 2.937, p = 0.026). The expression of TTF-1 was correlated with tumor differentiation in resected lung adenocarcinoma patients (p < 0.001). Five-year survival was 60.0% for score 1 TTF-1 expression patients, 80.1% for score 2 TTF-1 expression patients, and 86.1% for score 3 TTF-1 expression group patients. The lung cancer cell line study of knockdown and overexpression of TTF-1 revealed TTF-1 mediated High Mobility Group AT-Hook 2 (HMGA2) protein involved with epithelium-mesenchymal transformation. The chromatin immunoprecipitation revealed TTF-1 regulated HMGA2 via direct binding. TTF-1/HMGA2 axis was associated with tumor differentiation and mediated the aggressiveness of the tumor and prognosis.
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http://dx.doi.org/10.1038/s41598-017-14651-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660159PMC
October 2017
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