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Recently, many studies have indicated that ambient air particulate matter (PM) can increase the risk of oral cancer. The most common malignant tumor in the oral cavity is oral squamous cell carcinoma (OSCC). Usually, cancer cell migration/invasion is the most important cause of cancer mortality. Matrix metalloproteinase-2 (MMP-2) and MMP-9 have been shown to play important roles in regulating metastasis and the tumor microenvironment. Here, we studied the anti-cancer effects of surfactin, a cyclic lipopeptide generated by Bacillus subtilis, on cancer cell migration and invasion. Surfactin suppressed PM-promoted cell migration and invasion and colony formation of SCC4 and SCC25 human oral squamous cell carcinoma cell lines. We observed that PM induced MMP-2 and MMP-9 expression, which was inhibited by surfactin. Transfection with p65, p50, c-Jun, c-Fos, p85, p110, Akt, mammalian target of rapamycin (mTOR), or interleukin-6 (IL-6) siRNA markedly inhibited PM-induced MMP-2 and MMP-9 expression. Moreover, surfactin could reduce Akt, mTOR, p65, and c-Jun activation and IL-6 secretion induced by PM. Finally, we proved that transfection with Akt, p65, or c-Jun siRNA significantly inhibited PM-induced IL-6 release. Taken together, these results suggest that surfactin functions as a suppressor of PM-induced MMP2/9-dependent oral cancer cell migration and invasion by inhibiting the activation of phosphoinositide 3-kinase (PI3K)/Akt/mTOR and PI3K/Akt/nuclear factor-κB (NF-κB) and activator protein-1 (AP-1)/IL-6 signaling pathways.

Recently, ambient air particulate matter (PM) has been shown to increase the risk of oral cancer. The most common malignant tumor in the oral cavity is oral squamous cell carcinoma (OSCC). Recent studies have revealed that surfactin, a cyclic lipopeptide generated by Bacillus subtilis, has anti-inflammatory and anti-cancer properties. However, the exact anti-cancer effects of surfactin on human OSCC and underlying molecular mechanisms remain largely unknown. In the present study, we found that treatment of SCC4 and SCC25 cells (human OSCC cell lines) with surfactin reduced the viability of SCC4 and SCC25 cells by induction of apoptosis. Surfactin-induced apoptosis was associated with caspase activation and poly(ADP-ribose) polymerase (PARP) cleavage and was regulated by the mitochondrial pathway, exemplified by mitochondrial depolarization, mitochondrial-derived reactive oxidative species (ROS) production, cytochrome c release, up-regulation of Bad and Bax, and down-regulation of Bcl-2. Surfactin induced NADPH oxidase-dependent ROS generation, which appeared essential for the activation of the mitochondrial pathway. Surfactin-induced mitochondrial-derived ROS generation was associated with JNK1/2 activation. After treatment with surfactin, ROS caused JNK1/2-dependent cell death of SCC4 and SCC25 cells. Taken together, our findings suggest that surfactin induces mitochondria associated apoptosis of human OSCC cell lines, and surfactin may be a potential chemotherapeutic agent for future OSCC treatment.

Particulate matter (PM), a major air pollutant, may be associated with adverse cardiovascular effects. Reactive oxygen species- (ROS-) dependent proinflammatory cytokine production, such as interleukin-6 (IL-6), is a possible underlying mechanism. Carbon monoxide- (CO-) releasing molecule-2 (CORM-2) which liberates exogenous CO can exert many beneficial effects, particularly anti-inflammation and antioxidant effects. The purpose of this study was to explore the protective effects and underpinning mechanisms of CORM-2 on PM-induced aorta inflammation. Here, human aortic vascular smooth muscle cells (HASMCs) were utilized as in vitro models for the assessment of signaling pathways behind CORM-2 activities against PM-induced inflammatory responses, including Toll-like receptors (TLRs), NADPH oxidase, ROS, nuclear factor-kappa B (NF-κB), and IL-6. The modulation of monocyte adherence and HASMC migration, that are two critical cellular events of inflammatory process, along with their regulators, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and matrix metalloproteinase-2 (MMP-2) and MMP-9, in response to PM by CORM-2, were further evaluated. Finally, mice experiments under different conditions were conducted for the in vivo evaluation of CORM-2 benefits on the expression of inflammatory molecules including IL-6, ICAM-1, VCAM-1, MMP-2, and MMP-9. Our results found that PM could induce aorta inflammation in vitro and in vivo, as evidenced by the increase of IL-6 expression that was regulated by the TLR2 and TLR4/NADPH oxidase/ROS/NF-κB signaling pathway, thereby promoting ICAM-1- and VCAM-1-dependent monocyte adhesion and MMP-2- and MMP-9-dependent HASMC migration. Importantly, our experimental models demonstrated that CORM-2-liberated CO effectively inhibited the whole identified PM-induced inflammatory cascade in HASMCs and tissues. In conclusion, CORM-2 treatment may elicit multiple beneficial effects on inflammatory responses of aorta due to PM exposure, thereby providing therapeutic value in the context of inflammatory diseases of the cardiovascular system.

The accuracy of static guided implant surgery (sGIS) using conventional planning workflow has been extensively examined, however, more information is required to justify the application of fully digital planning protocol. The purpose of this study was to investigate the clinical accuracy of sGIS with a fully digital planning workflow. Twenty-one partially edentulous patients were enrolled in this prospective study. Cone-beam computed tomography (CBCT) and intraoral scans were taken and superimposed by matching the dental surface images directly (surface registration protocol) or by matching fiducial markers on a stereolithographic (SLA) radiographic template fabricated from the digital data of the intraoral scan (fiducial marker registration protocol). Virtual implant treatment plans were then determined, and tooth-supported SLA surgical guides were fabricated according to the plans. Twenty-six implant surgeries were performed via the surgical guide by one surgeon. Pre- and post-operative CBCT images were superimposed, and the positional and angular deviations between placed and planned implants were measured with metrology software. A total of 43 fully guided implants were placed, in which 25 implants were planned with the surface registration protocol. Implants planned based on the surface registration protocol had a larger mean angular deviation than the fiducial marker registration protocol. No significant differences were found for any deviations of the examined variables. Within the limits of this study, we concluded that the clinical accuracy of the sGIS planned with a fully digital workflow was consistent with the conventional workflow for partially edentulous patients.

Simple Summary The conventional methods that seek to predict clinical treatment response are based on the number of circulating tumor cells (CTCs) present in liquid biopsies or genetic profiling of extracted CTCs. This paper presents a novel process by which CTCs can be extracted from blood samples taken from head and neck cancer patients and then expanded ex vivo to form organoids that can be tested with a panel of anti-cancer treatments. The resulting drug sensitivity profiles derived from cisplatin treatment of organoids were subsequently found to correlate with clinical treatment response to cisplatin in patients. CTCs extracted from liquid biopsies for ex vivo expansion negates the need for complicated and potentially risky biopsies of tumor material, thereby supporting the application of this procedure for checkups and treatment monitoring. Abstract The advanced-stage head and neck cancer (HNC) patients respond poorly to platinum-based treatments. Thus, a reliable pretreatment method for evaluating platinum treatment response would improve therapeutic efficiency and outcomes. This study describes a novel strategy to predict clinical drug responses in HNC patients by using eSelect, a lab-developed biomimetic cell culture system, which enables us to perform ex vivo expansion and drug sensitivity profiling of circulating tumor cells (CTCs). Forty liquid biopsies were collected from HNC patients, and the CTCs were expanded ex vivo using the eSelect system within four weeks. Immunofluorescence staining confirmed that the CTC-derived organoids were positive for EpCAM and negative for CD45. Two illustrative cases present the potential of this strategy for evaluating treatment response. The statistical analysis confirmed that drug sensitivity in CTC-derived organoids was associated with a clinical response. The multivariant logistic regression model predicted that the treatment accuracy of chemotherapy responses achieved 93.75%, and the area under the curves (AUCs) of prediction models was 0.8841 in the whole dataset and 0.9167 in cisplatin specific dataset. In summary, cisplatin sensitivity profiles of patient-derived CTCs expanded ex vivo correlate with a clinical response to cisplatin treatment, and this can potentially underpin predictive assays to guide HNC treatments.

// Ming-Yi Lu 1, 2, * , Yi-Wen Liao 1, * , Pei-Yin Chen 1, 2 , Pei-Ling Hsieh 3 , Chih-Yuan Fang 4, 5 , Chia-Yu Wu 5, 6 , Ming-Liang Yen 6 , Bou-Yue Peng 5, 6 , Dayen Peter Wang 5, 6 , Hsin-Chung Cheng 5, 6 , Ching-Zong Wu 5, 6 , Yung-Hsun Shih 4, 6 , Duen-Jeng Wang 6 , Cheng-Chia Yu 1, 2, 3 and Lo-Lin Tsai 4, 6 1 School of Dentistry, Chung Shan Medical University, Taichung, Taiwan 2 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan 3 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan 4 Department of Dentistry, Taipei Municipal Wanfang Hospital, Taipei, Taiwan 5 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan 6 Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Cheng-Chia Yu, email: ccyu@csmu.edu.tw Lo-Lin Tsai, email: lolintsai@tmu.edu.tw Keywords: oral squamous cell carcinomas; long non-coding RNA; HOTAIR; cancer stem cells; mesenchymal Received: May 16, 2017 Accepted: August 26, 2017 Published: October 07, 2017 ABSTRACT Increasing evidence indicates that long non-coding RNAs (lncRNAs) regulate diverse cellular processes, such as cell growth, apoptosis and tumorigenesis. However, the functional roles of lncRNAs and mechanistic analysis of their interplays with oncogenic pathways in oral cancer remain largely unknown. In the current study, we examined the significance of lncRNA HOTAIR (HOX transcript antisense RNA) in tumor progression of oral squamous cell carcinomas (OSCC). We found the expression of HOTAIR was upregulated in tumor tissues, especially in the metastatic samples. And it was also observed in metastatic OSCC cell lines. Silence of HOTAIR in oral carcinomas stem cells (OCSC) significantly inhibited their cancer stemness, invasiveness and tumourigenicity in xenotransplantation models. By contrast, overexpression of HOTAIR in OSCC enhanced their metastatic potential and epithelial-mesenchymal transition (EMT) characteristics. And we showed that the expression of HOTAIR was positively related to mesenchymal markers and inversely correlated with epithelial marker in clinical samples. Moreover, Kaplan-Meier survival analysis suggested that high level of HOTAIR was a strong predictor of poor survival in OSCC patients. Collectively, our data demonstrated that HOTAIR-mediated cancer stemness and metastasis are associated with the regulation of EMT and HOTAIR may serve as a therapeutic target in OSCC.

In this paper, we fabricate a surface acoustic wave (SAW) device with micro-structures on a zinc oxide (ZnO) thin film and measure its signal response. The manufacturing processes of the SAW device include the fabrication of micro-structures of a SAW element and its interdigital transducer by silicon micro-machining and the fabrication of a thin film of ZnO by RF magnetron sputtering. We, then, measure the SAW properties. This research investigates the properties of sputtered thin films for various amounts of O2/(Ar + O2) using Zn and ZnO targets. Regardless of target, the growth rate of the ZnO thin film decreases as the oxygen content increases. When the SAW is sputtered ZnO thin film using 30% oxygen, the digital signal of the SAW has better performance. The measurement signal of the SAW with micro-structures is similar to that without micro-structures.

Simple Summary Particulate matter, especially the fine fraction PM2.5, is officially stated as carcinogenic to human. There are compelling evidences on the association between PM2.5 exposure and lung cancer, and there are also some preliminary data reporting the significant links between this fraction with non-lung cancers. The underlying mechanisms remain unclear. Further studies related to such scope are highly required. The purpose of this work is to systemically analyze recent findings concerning the relationship between PM2.5 and cancer, and to thoroughly present the oxidative stress pathways mediated by reactive oxygen species as the key mechanism for carcinogenesis induced by PM2.5. This will provide a more comprehensive and updated knowledge regarding carcinogenic capacity of PM2.5 to both clinicians and public health workers, contributing to preventive and therapeutic strategies to fight against cancer in human. Abstract Cancer is one of the leading causes of premature death and overall death in the world. On the other hand, fine particulate matter, which is less than 2.5 microns in aerodynamic diameter, is a global health problem due to its small diameter but high toxicity. Accumulating evidence has demonstrated the positive associations between this pollutant with both lung and non-lung cancer processes. However, the underlying mechanisms are yet to be elucidated. The present review summarizes and analyzes the most recent findings on the relationship between fine particulate matter and various types of cancer along with the oxidative stress mechanisms as its possible carcinogenic mechanisms. Also, promising antioxidant therapies against cancer induced by this poison factor are discussed.

Purpose. Astaxanthin (AST) has a strong antioxidant cellular membrane chaperone protective effect. Recently, a water-soluble nanosized AST (nano-AST) form was produced, which is expected to improve the efficacy of oral intake effects. The purpose of this study was to examine whether oral nano-AST has therapeutic effects on UV-induced photokeratitis in mice.Methods. C57BL/6 mice were administered twice with either nano-AST, AST oil, lutein, or bilberry extracts 3 hours before and shortly before UV irradiation (dose: 400 mJ/cm2). The corneas were collected 24 hours after irradiation and stained with H&E and TUNEL. NF-κB, dihydroethidium (DHE), COX-2, p-IκB-α, TNFα, and CD45 expression were evaluated through immunohistochemistry, Western blot analysis, and qPCR.Results. Corneal epithelium was significantly thicker in mice orally administered with nano-AST than in the others (p<0.01), with significantly less NF-κB nucleus translocation (p<0.001), and significantly fewer TUNEL cells (p<0.01). Weaker DHE signals were detected in the nano-AST group (p<0.05) relative to the others. Furthermore, reduced inflammation and decreased cell death in corneal tissue were observed in the nano-AST group, as indicated by a reduction in the expression of COX-2, p-IκB-α, TNFα, and CD45.Conclusions. Oral administration of nano-AST demonstrated a protective effect on UV-induced photokeratitis via antioxidative, anti-inflammatory, and antiapoptotic activity.

In this study, we elucidated the effect of heat treatment on the microstructures and damping properties of the biomedical Mg–1 wt% Zr (K1) alloy by optical microscopy, transmission electron microscopy, energy-dispersive X-ray spectrometry, and experimental model analysis. The following microstructural transformation occurred when the as-quenched (AQ, i.e., solution heat treated and quenched) K1 alloy was subjected to aging treatment in the temperature range 200–500 °C: α-Mg → (α-Mg + twin dense ) → (α-Mg + twin loose ) → (α-Mg + α-Zr). This microstructural transformation was accompanied by variations in the damping capacity. The damping properties of the AQ K1 alloy subjected to aging treatment at 300 °C for 16 h were the best among those of the alloys investigated in the present study. The presence of twin structures in the alloy matrix was thought to play a crucial role in increasing the damping capacity of the K1 alloy. Hence, we state that a combination of solution treatment and aging is an effective means of improving the damping capacity of biomedical K1 alloys.

This work reports a novel and effective procedure for manufacturing the mold insert of microlens arrays. First, the microlens arrays master is formed using room-temperature imprint lithography and photoresist reflow process. Next, electroforming is carried out to fabriccate the metal mold insert from the master. Finally, microinjection molding is used to replicate the molded microlens arrays. The 200 × 200 arrays of molded microlens, with a diameter of 150 μm, a pitch of 200 μm, and a sag height of 11.29 μm for polycarbonate (PC) material and 11.24 μm for polymethylmethacrylate (PMMA) material have been successfully fabricated. The moldability for PMMA material is better than PC material on molded microlens arrays. The average surface roughness of the molded microlens arrays is 4.53 nm for PMMA material and 4.81 nm for PC material. The mold temperature is the most important processing factor for the focal length and sag height of molded microlens arrays. POLYM. ENG. SCI., 2011. © 2010 Society of Plastics Engineers.

The purpose of this study is to develop a three-dimensional (3D) finite element model of the temporomandibular joint (TMJ) and to further investigate the stress distributions after occlusal splint therapy. Six patients with anterior disc displacement without reduction were reconstructed before and after six months of occlusal splint treatments from computed topography (CT) and magnetic resonance imaging (MRI). One must focus on the magnitude and location of the maximum stresses under physiological loading. In the 3D model studies, each mandibular condyle, disc, and articular eminence was divided into five regions: anterior, posterior, central, medial, and lateral. The results of this study show that the abnormal von Mises stresses occurred in the condyle during jaw closing, and overloading of the anterior condyle and posterior disc during jaw opening occurred before treatment. Stresses of all regions became well distributed after treatment, and an approximately 30% stress reduction in the condyle and a 35% stress reduction in the disc were found during jaw opening (p < 0.05), a remarkable difference. This result shows the potential clinical benefits in terms of proven superior biomechanical behavior according to occlusal splint treatment.

Both periodontitis and osteoporosis have similar sign of bone resorption in nature. However, the relationship of the severity between these 2 bone-loss diseases is still uncertain. The aim of this study was to investigate the association between the severity of osteoporosis and periodontitis regarding the impact of oral hygiene maintenance. In total, 35,127 osteoporosis patients and 50,498 comparisons were derived from the Longitudinal Health Insurance Database of Taiwan between 2000 and 2010. The population was subdivided into groups according to the different level oral hygiene maintenance and the severity of periodontitis and osteoporosis. The association between osteoporosis and periodontitis was estimated by multinomial logistic regression and rank correlation by Kendall rank correlation test, presented by odds ratio (OR), and 5% confidence intervals (CIs). After controlling the age, sex, and comorbidities, variables in the good oral hygiene maintenance population, we found that periodontitis raised 1.29-fold risk of osteoporosis (95% CI = 1.12–1.49); the risk of osteoporosis was increased with the elevated severity of periodontitis from 1.27 (95% CI = 1.08–1.48) to 1.38 (95% CI = 1.01–1.89). There is a positive correlation between the severity of periodontitis and osteoporosis occurrence in this population (OR = 1.27–1.46; Kendall rank correlation test P = 0.0003). In the poor oral hygiene maintenance population, periodontitis patients had 6.02-fold risk of osteoporosis than those who without periodontitis (95% CI = 4.65–7.81); the risk of osteoporosis was increased with periodontitis severity from 5.96 (95% CI = 4.48–7.92) to 6.37 (95% CI = 3.36–12.1). This result indicated the periodontitis and osteoporosis are conjunctive. The sudden periodontal breakdown of those who with good oral hygiene maintenance might be an indicator for the risk of osteoporosis; if those who were diagnosed as osteoporosis must pay more attention to their periodontal health. Good oral hygiene maintenance might be a crucial factor for preventing the deterioration of osteoporosis progressing; the oral hygiene maintenance plays a significant influence on the association between periodontitis and osteoporosis.

A 67-year-old man on maintenance hemodialysis for 8 years was found to have a high serum intact parathyroid hormone (i-PTH, >1550 pg/ml) level. The serum phosphate and calcium levels were 7.1 and 10.1 mg/dl, respectively. He was diagnosed with secondary hyperparathyroidism. Despite treatment with intravenous vitamin D therapy and phosphate binders, the hyperparathyroidism remained refractory to medical treatment. He was referred to our hospital for further management.

Background and Aims Little is currently known about the risk of developing bisphosphonate-related osteonecrosis of the jaw (BRONJ). This study sought to determine the incidence of BRONJ in osteoporotic patients. We also sought to identify the nature and types of risk factors of osteonecrosis of jaw (ONJ) related to the use of oral bisphosphonates (BPs). Materials and Methods Data from the National Health Insurance system of Taiwan. This cohort study included 19,399 adult osteoporosis patients received dental extraction in 2000-2010 (osteoporosis cohort) and 38,669 age and gender matched comparisons selected from dental extraction people without osteoporosis and osteonecrosis history (comparison cohort). All study subjects were followed from the date of their dental extraction (index date) to the development of ONJ and were included in the study up to 2011 or were lost to the study, whichever occurred first. Cox proportional hazard regression was used to estimate the hazard ratio and 95% confidence intervals for the two cohorts. Results Patients with osteoporosis had a significantly higher risk to develop ONJ than healthy persons (adjusted HR, 2.05; 95% confidence interval, 1.58–2.65). The risk of ONJ increased with the severity of osteoporosis, no matter whether patient with cancer or not. A cumulative effect of dental extraction frequency may increase the risk of ONJ. Conclusions We concluded that ONJ is caused by a number of factors. Osteoporosis and past dental history play the very important roles, while BPs play the synergistic effect.

Cheng-Jui Lin, Han-Hsiang Chen, Kuo-Song Chang, Cheng-Yi Hsu, Yi-Chou Chen and Chih-Jen Wu Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; Department of Emergency Medicine, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Medicine, Nursing and Management College, Taipei, Taiwan and Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan

Nanocrystalline diamond (NCD) films were synthesized using microwave plasma chemical vapor deposition procedure with the CH4/Ar/H2 gas mixture on silicon substrate at moderate temperatures in the present study. The characteristics of NCD films were evaluated using scanning electron microscopy, Raman spectroscopy, transmission electron microscopy, optical emission spectroscopy and optical contact angle meter. The analytical results revealed that C2 radial was the dominant species in the deposited process. From TEM observation the NCD films was formed via the etching of hydrocarbons and a small amount of hydrogen content additive into gas mixture could improve the aggregation of the nucleation film to form the NCD films. A (crystalline → amorphous-like → nanocrystalline structure) transition occurred during formation of NCD films. The more hydrophobic surfaces implied that NCD films were the potential biomaterial in the application of article heart valve or stent.