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Periodontitis is a chronic disease associated with dental biofilm formation by bacteria. The primary clinical signs include plaque formation, gingivitis, gingival bleeding, and attachment loss. P-113, a 12-amino acid antimicrobial peptide, is derived from Histatin 5 (Hst5) secreted by the human parotid and submandibular salivary glands and has been reported to reduce plaque formation, gingivitis, and gingival bleeding. This study aimed to investigate the effect of P-113 on periodontal disease-associated bacteria and the relative abundance of bacteria using real-time polymerase chain reaction (real-time PCR) and Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Saliva samples were collected from participants for analyses. Real-time PCR results showed significant changes in the abundance of the periodontal disease-associated bacteria, Fusobacterium nucleatum and Tannerella forsythia, after the use of the P-113 mouthwash. After culturing in an anaerobic environment, MALDI-TOF MS analysis was performed. The results showed that the relative abundance of Streptococcus mitis decreased and that of beneficial Streptococcus salivarius increased after the use of the P-113 mouthwash. These results indicate the potential of P-113 mouthwash as a treatment that can influence the proportion of pathogens and probiotics to establish equilibrium in the salivary environment.

Background: With the development of medicine and technological advancement, the concept of precision medicine is becoming popular, and the traditional principle of all-in-one therapy has been gradually fading. Utilizing the detection of genome, transcriptome, proteome, and metabolome, combined with big data analysis to discover new pathogenic mechanisms, provides more effective prescriptions with fewer side effects and even shifts the emphasis of medicine from disease treatment to disease prevention. Methods: Proteomics is one of the potential tools for monitoring the alternations of protein expression. This study analyzed the proteomic alternations between normal colon tissue and cancerous colon tissue via two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to select the potential target proteins. Results: The experimental results demonstrated that a total of 90 proteins were identified, which were significantly expressed. These proteins were classified according to their functions. They were found to be mainly associated with cytoskeleton regulation, glycolysis, and protein folding. Furthermore, immunoblotting was used to verify the differentially expressed proteins, and the results were in line with the trends in the proteomic analysis. Conclusion: To sum up, these differentially expressed proteins could be used as potential and precise biomarkers in the diagnosis or treatment of colorectal cancer.

More than 70% of patients with ovarian cancer are diagnosed in advanced stages. Therefore, it is urgent to identify a promising prognostic marker and understand the mechanism of ovarian cancer metastasis development. By using proteomics approaches, we found that UDP‐glucose dehydrogenase (UGDH) was up‐regulated in highly metastatic ovarian cancer TOV21G cells, characterized by high invasiveness (TOV21GHI), in comparison to its parental control. Previous reports demonstrated that UGDH is involved in cell migration, but its specific role in cancer metastasis remains unclear. By performing immunohistochemical staining with tissue microarray, we found overexpression of UGDH in ovarian cancer tissue, but not in normal adjacent tissue. Silencing using RNA interference (RNAi) was utilized to knockdown UGDH, which resulted in a significant decrease in metastatic ability in transwell migration, transwell invasion and wound healing assays. The knockdown of UGDH caused cell cycle arrest in the G0/G1 phase and induced a massive decrease of tumour formation rate in vivo. Our data showed that UGDH‐depletion led to the down‐regulation of epithelial‐mesenchymal transition (EMT)‐related markers as well as MMP2, and inactivation of the ERK/MAPK pathway. In conclusion, we found that the up‐regulation of UGDH is related to ovarian cancer metastasis and the deficiency of UGDH leads to the decrease of cell migration, cell invasion, wound healing and cell proliferation ability. Our findings reveal that UGDH can serve as a prognostic marker and that the inhibition of UGDH is a promising strategy for ovarian cancer treatment.

Yuan He,1,2 Zhi-Jun Duan,1 Cheng-Fang Wang,2 Yu-Shan Wei,3 Ming-Xu Cai2 1Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China; 2Healthcare Management Center, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China; 3Department of the Scientific Research Management, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of ChinaCorrespondence: Zhi-Jun DuanDepartment of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of ChinaTel/Fax +86 41183635963Email duanzhijun12@outlook.com; cathydoctor@sina.comObjective: The present study aimed to explore the relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and gastroesophageal reflux symptoms (GERS).Methods: The present study was a cross-sectional observational study. The study population was 3002 subjects from a single hospital who underwent a health checkup from September 1, 2019, to December 31, 2020. The diagnosis of MAFLD was based on the diagnosis of fatty liver in the subject by ultrasound or computed tomography (CT) and the presence of one of the following conditions: overweight or obesity (body mass index [BMI] ≥ 23), type 2 diabetes mellitus, and metabolic abnormalities. The subjects were divided into the GERS group (n = 305) and the non-GERS group (n = 2697) based on the presence or absence of GERS, based on the GerdQ score.Results: The prevalence of MAFLD was significantly higher in the GERS group than in the non-GERS group (p = 0.001). In the univariate analysis of risk factors for GERS, MAFLD was identified as a risk factor for GERS (OR 1.5; 95% CI 1.176– 1.913; p = 0.001). With adjustment of confounding factors such as BMI, waist circumference, lipid levels, and blood pressure, the correlation between MAFLD and GERS was attenuated but still significant (OR 1.408; 95% CI 1.085– 1.826; p = 0.010).Conclusion: MAFLD might be an independent risk factor for GERS.Keywords: gastroesophageal reflux symptoms, GERD, metabolic dysfunction-associated fatty liver disease, body mass index, obesity, questionnaire

Simple Summary The gypsy moth, Lymantria dispar is one of the main forest defoliators worldwide. The baculovirus, Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV), can naturally control this pest and is safe to non-target organisms. However, Toll-like receptor (TLR) signaling pathway, which plays a critical role in innate immunity both in vertebrates and invertebrates, and its underlying immune mechanism against LdMNPV invasion in L. dispar have not been investigated. In this study, eleven TLRs and five downstream TLR pathway components of L. dispar were identified. All of these proteins comprised typical domain architecture. Primary and tertiary structure analysis revealed that Toll/interleukin-1 receptor (TIR) domains of TLRs from L. dispar were conserved during evolution. Expression analysis showed that several TLRs and all identified downstream genes of TLR pathway in L. dispar were significantly up-regulated in response to LdMNPV infection, implying that the TLR pathway of L. dispar was activated and may be involved in L. dispar innate immunity against LdMNPV infection. Taken together, this research contributed to the clarification of innate immunity in L. dispar. Abstract The gypsy moth, Lymantria dispar, is a polyphagous forest pest worldwide. The baculovirus, Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV) is a natural pathogen of L. dispar. The Toll-like receptors (TLR) pathway plays a crucial role in both innate and adaptive immunity in animals. However, The TLR pathway and its underlying immune mechanism against baculovirus in L. dispar have not been explored. In this study, eleven TLRs and five downstream TLR pathway components were identified and characterized from L. dispar. Structural analysis indicated that intracellular Toll/interleukin-1 receptor (TIR) domains of LdTLRs and LdMyD88 contained three conserved motifs, and the 3D structures of TIR domains of LdTLRs possessed similar patterns in components arrangement and spatial conformation. The TLR proteins of L. dispar were placed into five monophyletic groups based on the phylogenetic analysis. LdTLR1, 2, 5, 6, 7, 8 and all identified downstream TLR pathway factors were highly induced upon LdMNPV infection, indicating that the TLR pathway of L. dispar was activated and might play a role in the immune response to LdMNPV infection. Collectively, these results help elucidate the crucial role of the TLR pathway in the immune response of L. dispar against LdMNPV, and offer a foundation for further understanding of innate immunity of the pest.

Antrodia cinnamomea (AC) is a nutraceutical fungus and studies have suggested that AC has the potential to prevent or alleviate diseases. However, little is known about the AC-induced phenotypes on the intestine-liver axis and gut microbial alterations. Here, we performed two-dimensional difference gel electrophoresis (2D-DIGE) and MALDI-Biotyper to elaborate the AC-induced phenotypes on the intestine-liver axis and gut microbial distribution of C57BL/6 mice. The experimental outcomes showed that the hepatic density may increase by elevating hepatic redox regulation, lipid degradation and glycolysis-related proteins and alleviating cholesterol biosynthesis and transport-related proteins in C57BL/6 mice with AC treatment. Moreover, AC facilitates intestinal glycolysis, TCA cycle, redox and cytoskeleton regulation-related proteins, but also reduces intestinal vesicle transport-related proteins in C57BL/6 mice. However, the body weight, GTT, daily food/water intake, and fecal/urine weight were unaffected by AC supplementation in C57BL/6 mice. Notably, the C57BL/6-AC mice had a higher gut microbial abundance of Alistipes shahii (AS) than C57BL/6-Ctrl mice. In summary, the AC treatment affects intestinal permeability by regulating redox and cytoskeleton-related proteins and elevates the gut microbial abundance of AS in C57BL/6 mice that might be associated with increasing hepatic density and metabolism-related proteins of the liver in C57BL/6 mice. Our study provides an insight into the mechanisms of AC-induced phenotypes and a comprehensive assessment of AC's nutraceutical effect in C57BL/6 mice.

In this study, we aimed to identify the cultivatable oral anaerobic bacterial distribution in oral cavity by MALDI-TOF Biotyper. The bacterial distribution of three groups, including subjects with/without periodontal disease, two clusters of age (60 years as the cutoff), and before/after treatment, were investigated in this study. There were 38 participants recruited in this study, involving 18 subjects with moderate to severe periodontal-infected patients and 20 healthy controls. Total number of 126 bacterial species were identified by MALDI-TOF MS. The relative abundance of Streptococcus gordonii and Streptococcus intermedius in periodontal patients is higher than healthy controls indicating potential biomarkers for periodontal disease. Participants with periodontal disease were subdivided in to two clusters of age (60 years as the cutoff), 11 and 7 participants were age60 years and60 years, respectively. Meanwhile, the incidence of Streptococcus pneumoniae and Streptococcus oralis infection were higher in the subjects above 60 years old than below. Moreover, the bacterial distribution between pre-treatment and post-treatment was similar indicating that basic treatment without the ability to redistribute the microbiota. In summary, the cultivable oral anaerobic bacteria were identified by MALDI-TOF MS and the bacterial distribution shifting was shown to be associated with the progress of periodontal disease to aging and basic treatment. This study provided information for diagnosis and treatment guidelines for oral healthcare.

This study investigates how corporate entity directors and supervisors from business groups influence real earnings management (REM) by using a sample of firms listed on the Taiwan Stock Exchange. ...

With the concept of precision medicine, combining multiple molecular-targeting therapies has brought new approaches to current cancer treatments. Malfunction of the tumor suppressor protein, p53 is a universal hallmark in human cancers. Under normal conditions, p53 is degraded through an ubiquitin-proteosome pathway regulated by its negative regulator, MDM2. In contrast, cellular stress such as DNA damage will activate p53 to carry out DNA repair, cell cycle arrest, and apoptosis. In this study, we focused on ovarian carcinoma with high EGFR and MDM2 overexpression rate. We assessed the effects of combined inhibition by MDM2 (JNJ-26854165) and EGFR (gefitinib) inhibitors on various ovarian cell lines to determine the importance of these two molecular targets on cell proliferation. We then used a proteomic strategy to investigate the relationship between MDM2 and EGFR inhibition to explore the underlying mechanisms of how their combined signaling blockades work together to exert cooperative inhibition. Our results demonstrated that all four cell lines were sensitive to both individual and combined, MDM2 and EGFR inhibition. The proteomic analysis also showed that gefitinib/JNJ-treated CAOV3 cells exhibited downregulation of proteins involved in nucleotide biosynthesis such as nucleoside diphosphate kinase B (NME2). In conclusion, our study showed that the combined treatment with JNJ and gefitinib exerted synergistic inhibition on cell proliferation, thereby suggesting the potential application of combining MDM2 inhibitors with EGFR inhibitors for enhancing efficacy in ovarian cancer treatment.

Purpose The purpose of this paper is to examine the ethical investment willingness decision-making process to understand how investors evaluate corporate social responsibility (CSR) actions. Design/methodology/approach Data were collected through a survey of 298 individual investors and analyzed using structural equation modeling. Findings Results reveal that perfectionist decision-making style is positively related to perceived moral intensity, substitutability of financial returns, and ethical investment willingness. In addition, perceived moral intensity and substitutability of financial returns are positively related to ethical investment willingness. Finally, perceived moral intensity is positively related to substitutability of financial returns, and a two-factor causal mediation model is supported. Research limitations/implications The limitation of this study was that the pre-tests and sampling methods required all participants to have investing experience; however, procurement of trading information for each investor was impossible; thus, actual investment behaviors were undetermined. This study shed light on the mediating roles of perceived moral intensity and the substitutability of financial returns. Future studies can further investigate the factors influencing perceived moral intensity and the substitutability of financial returns. Practical implications Future ethical investment education can focus on cultivate the ability to distinguish ethical investments and change ethical investment willingness into actual investment behavior. Originality/value Understanding the relationship between these variables can help understand why ethical investment willingness varies among investors and how the traditional financial theory investment decision model should be revised as, internationally, more people have begun to observe CSR and sustainable development.

This study investigated the performance of individual departments and the efficiency of resource utilization in tax offices. The results can be used to improve the performance of tax offices and to increase tax revenues. In this study, the operational flow of local tax offices was divided into two stages: tax collection and tax management. Network data envelopment analysis (NDEA) and a Russell directional distance function were used to evaluate operating efficiency in departments of 20 Taiwanese local tax offices for 2013. The results indicated that, first, efficiency was significantly different for tax collection and tax management. Second, the input inefficiency of tax collection was mainly due to total floor area, which was 15% larger than required, and the input inefficiency of tax management was mainly due to total floor area (23% larger than required), followed by direct labour input (19% larger than required). Finally, on average, the amount of collected property transfer taxes was 23% smaller than required. The model used in the present study included undesirable outputs. The findings indicated that the highest levels of overall inefficiency were due to inability to collect taxes (intermediate outputs) in Hsinchu County (9.27%), Chiayi County (3.25%) and Pingtung County (20.44%), which required reduction in the number of instances of inability to collect property taxes by 5619, 1258 and 12 350 cases, respectively. In total, 19 227 fewer cases of uncollectable property taxes in Taiwan would indicate improved arrears settlement and tax prevention measures.

Oral microbes are a contributing factor to hyperglycemia by inducing an increase in insulin resistance resulting in uncontrolled blood glucose levels. However, the relationship between the distribution of oral flora and hyperglycemia is still controversial. Combining the power of MALDI-Biotyper with anaerobic bacterial culture, this study explores the correlation between anaerobic bacteria in the oral cavity and blood glucose levels. The results demonstrated that altered blood glucose levels contributed to a varied bacterial distribution in the oral cavity. Specifically, Veillonella spp. and Prevotella spp. were identified in a higher proportion in people with elevated blood glucose levels. Six bacterial species identified in this study (Prevotella melaninogenica, Campylobacter rectus, Streptococcus gordonii, Streptococcus mitis, Streptococcus salivarius, and Veillonella parvula) not only demonstrated a positive association with higher blood glucose levels, but also likely contribute to the development of the condition. The data demonstrated MALDI-TOF MS to be a simpler, faster, and more economical clinical identification tool that provides clarity and depth to the research on blood glucose and oral microbiota.

Antrodia Cinnamomea is a fungus species widely used as a herb medicine for hypertension, cancer and handover. Nevertheless, the biological roles of Antrodia Cinnamomea on the molecular mechanism of liver cancer are not entirely understood. To determine whether Antrodia Cinnamomea is able to be used for the treatment of liver cancer and its molecular mechanism, we examined the effect of Antrodia Cinnamomea on the differential proteomic patterns in liver cancer cell lines HepG2 and C3A as well as in Chang's liver cell, a normal liver cell, using quantitative proteomic approach. The proteomic analysis demonstrated that abundance of 82, 125 and 125 proteins was significantly altered in Chang's liver cells, C3A and HepG2, respectively. The experimental outcomes also demonstrated that Antrodia Cinnamomea-induced cytotoxicity in liver cancer cells mostly involved dysregulation of protein folding, cytoskeleton regulation, redox-regulation, glycolysis pathway as well as transcription regulation. Further analysis also revealed that Antrodia Cinnamomea promoted misfolding of intracellular proteins and dysregulate of cellular redox-balance resulting in ER-stress. To sum up our studies demonstrated that the proteomic strategy used in this study offered a tool to investigate the molecular mechanisms of Antrodia Cinnamomea-induced liver cancer cytotoxicity. The proteomic results might be further evaluated as prospective targets in liver cancer treatment.

// Shun-Hong Huang 1 , Ching-Hsuan Law 1 , Ping-Hsueh Kuo 2 , Ren-Yu Hu 1 , Ching-Chieh Yang 3, 4 , Ting-Wen Chung 1 , Ji-Min Li 1 , Li-Hsun Lin 1 , Yi-Chung Liu 1, 12 , En-Chi Liao 1 , Yi-Ting Tsai 1 , Yu-Shan Wei 1 , Chi-Chen Lin 5, 6, 7, 8 , Chien-Wen Chang 9 , Hsiu-Chuan Chou 10 , Wen-Ching Wang 2 , Margaret Dah-Tsyr Chang 2 , Lu-Hai Wang 11 , Hsing-Jien Kung 11 , Hong-Lin Chan 1, 2 , Ping-Chiang Lyu 1, 2 1 Department of Medical Sciences and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan 2 Department of Medical Sciences and Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan 3 Department of Radiation Oncology, Chi-Mei Medical Center, Tainan, Taiwan 4 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 5 Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan 6 Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan 7 Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan 8 Division of Chest Medicine. Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan 9 Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Taiwan 10 Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan 11 Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County, Taiwan 12 Institute of Population Sciences, National Health Research Institutes, Miaoli County, Taiwan Correspondence to: Hong-Lin Chan, e-mail: hlchan@life.nthu.edu.tw Ping-Chiang Lyu, e-mail: pclyu@mx.nthu.edu.tw Keywords: ECM, EMT, IF, MMP-13, OSCC Received: November 23, 2015 Accepted: February 09, 2016 Published: March 06, 2016 ABSTRACT The oral cancer cell line OC3-I5 with a highly invasive ability was selected and derived from an established OSCC line OC3. In this study, we demonstrated that matrix metalloproteinases protein MMP-13 was up-regulated in OC3-I5 than in OC3 cells. We also observed that expression of epithelial–mesenchymal transition (EMT) markers including Twist, p-Src, Snail1, SIP1, JAM-A, and vinculin were increased in OC3-I5 compared to OC3 cells, whereas E-cadherin expression was decreased in the OC3-I5 cells. Using siMMP-13 knockdown techniques, we showed that siMMP-13 not only reduced the invasion and migration, but also the adhesion abilities of oral cancer cells. In support of the role of MMP-13 in metastasis, we used MMP-13 expressing plasmid-transfected 293T cells to enhance MMP-13 expression in the OC3 cells, transplanting the MMP-13 over expressing OC3 cells into nude mice led to enhanced lung metastasis. In summary, our findings show that MMP-13 promotes invasion and metastasis in oral cancer cells, suggesting altered expression of MMP-13 may be utilized to impede the process of metastasis.

Oxidative stress provides a major contribution to the pathogenesis of glaucoma and may induce retinal ganglion cell (RGC) damage. Transforming growth factor β (TGF-β) has appeared as a neuroprotective protein in various indignities. However, the TGF-β mechanism of protective effects against oxidative stress damage in RGCs still undetermined. In our research, we investigated the regulatory mechanisms and potential effects of TGF-β1 & TGF-β2 in hydrogen peroxide (H2O2)-stimulated oxidative stress of RGCs in vitro. By a series of cell functional qualitative analysis, such as MTT cell viability assay, wound healing ability assay, apoptosis assay, intracellular ROS detection, immunoblot analysis, intracellular GSH content, and high-resolution respirometry, we illustrated the cell state in oxidative stress-induced injury. Results of protein expression showed that TGF-β1 & TGF-β2 was upregulated in RGCs after H2O2 stimulation. Cell functional assays resulted that knockdown of TGF-β1 & TGF-β2 reduced survival rate whereas enhanced apoptosis and accumulation of reactive oxygen species (ROS). Especially TGF-β1 upregulation promoted the protein expression of aldehyde dehydrogenase 3A1 (ALDH3A1) and increased the activity of antioxidant and neuroprotection pathways. Additionally, TGF-β1 & TGF-β2 on antioxidant signaling was related to activation of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor (Nrf2), which are stress-response proteins. ROS accumulation followed by the accumulation of hypoxia-inducible factor (HIF-1α) caused mitochondrial damage and led to neurodegeneration. In summary, our results demonstrated that TGF-β1 preserves RGCs from free radicals-mediated injury by upregulating the activation of Nrf2 expression and HO-1 signaling balance HIF-1α upregulation, implying a prospective role of TGF-β1 in retinal neuroprotection-related therapies.

A characteristic of diabetes mellitus is hyperglycemia, which is considered with an emphasis on the diabetic retinopathy of progressive neurodegenerative disease. Retinal ganglion cells (RGCs) are believed to be important cells affected in the pathogenesis of diabetic retinopathy. Transforming growth factor-beta (TGF-&beta, ) is a neuroprotective protein that helps to withstand various neuronal injuries. To investigate the potential roles and regulatory mechanisms of TGF-&beta, in hyperglycemia-triggered damage of RGCs in vitro, we established RGCs in 5.5, 25, 50, and 100 mM D-glucose supplemented media and focused on the TGF-&beta, related oxidative stress pathway in combination with hydrogen peroxide (H2O2). Functional experiments showed that TGF-&beta, 1/2 protein expression was upregulated in RGCs with hyperglycemia. The knockdown of TGF-&beta, enhanced the accumulation of reactive oxygen species (ROS), inhibited the cell proliferation rate, and reduced glutathione content in hyperglycemia. Furthermore, the results showed that the TGF-&beta, mediated enhancement of antioxidant signaling was correlated with the activation of stress response proteins and the antioxidant pathway, such as aldehyde dehydrogenase 3A1 (ALDH3A1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor (Nrf2), and hypoxia-inducible factor (HIF-1&alpha, ). Summarizing, our results demonstrated that TGF-&beta, keeps RGCs from hyperglycemia-triggered harm by promoting the activation of the antioxidant pathway, suggesting a potential anti-diabetic therapy for the treatment of diabetic retinopathy.

Cancer metastasis is the major cause of death in pancreatic cancer. We have established a pair of pancreatic ductal adenocarcinoma cell line, PANC1 and invasive PANC1-I5, as a model system toinvestigate the metastatic mechanism as well as potential therapeutic targets in pancreatic cancer. We used proteomic analysis based on two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to examine the global protein expression alterations between PANC1 and PANC1-I5. Proteomic study revealed that 88 proteins are differentially expressed between PANC1-I5 and PANC1 cells, and further functional evaluations through protein expression validation, gene knockout, migration and invasion analysis revealed that galectin-1 is one of the potential players in modulating pancreatic cancer metastasis. To conclude, we have identified numerous proteins might be associated with pancreatic cancer invasiveness in the pancreatic cancer model.

Aims Honokiol is a natural product extracted from herbal plants such as the Magnolia species which have been shown to exhibit anti-tumor and anti-metastatic properties. However, the effects of honokiol on thyroid cancers are largely unknown. Materials and methods To determine whether honokiol might be useful for the treatment of thyroid cancer and to elucidate the mechanism of toxicity of honokiol, we analyzed the impact of honokiol treatment on differential protein expression in human thyroid cancer cell line ARO using lysine-labeling two-dimensional difference gel electrophoresis (2D-DIGE) combined with mass spectrometry (MS). Key findings This study revealed 178 proteins that showed a significant change in expression levels and also revealed that honokiol-induced cytotoxicity in thyroid cancer cells involves dysregulation of cytoskeleton, protein folding, transcription control and glycolysis. Significance Our work shows that combined proteomic strategy provides a rapid method to study the molecular mechanisms of honokiol-induced cytotoxicity in thyroid cancer cells. The identified targets may be useful for further evaluation as potential targets in thyroid cancer therapy.

Evodiamine is a natural product extracted from herbal plants such as Tetradium which has shown to have anti-fat uptake and anti-proliferation properties. However, the effects of evodiamine on the behavior of thyroid cancers are largely unknown. To determine if evodiamine might be useful in the treatment of thyroid cancer and its cytotoxic mechanism, we analyzed the impact of evodiamine treatment on differential protein expression in human thyroid cancer cell line ARO using lysine-labeling two-dimensional difference gel electrophoresis (2D-DIGE) combined with mass spectrometry (MS). This study demonstrated 77 protein features that were significantly changed in protein expression and revealed evodiamine-induced cytotoxicity in thyroid cancer cells involves dysregulation of protein folding, cytoskeleton, cytoskeleton regulation and transcription control. Our work shows that this combined proteomic strategy provides a rapid method to study the molecular mechanisms of evodiamine-induced cytotoxicity in thyroid cancer cells. The identified targets may be useful for further evaluation as potential targets in thyroid cancer therapy.

Peripheral arterial occlusive disease (PAOD), one of the major manifestations of systemic atherosclerosis, causes intermittent claudication and rest pain. Patients with PAOD not only have reduced quality of life, but also have a substantial risk of cardiovascular morbidity and death. In this study, we adopted a proteomics-based approach using 2D-DIGE and MALDI-TOF MS to compare the differential plasma proteome between good and poor prognosis of PAOD. We identified 196 plasma proteins, which represent 42 unique gene products. These proteins mainly have roles in the inflammatory response and coagulation. This approach identified several potential prognostic plasma markers in PAOD, including transthyretin and complement factor B, which may be associated with the evaluation of good/poor prognosis of PAOD. In conclusion, we report a comprehensive patient-based plasma proteomic approach for the identification of potential plasma biomarkers for the screening and detection of good/poor prognosis of PAOD. Among these, transthyretin and complement factor B are potential markers for monitoring the PAOD disease in the plasma.

Glaucoma is a group of eye diseases that can cause vision loss and optical nerve damage. To investigate the protein expression alterations in various intraocular tissues (i.e., the cornea, conjunctiva, uvea, retina, and sclera) during ischemia–reperfusion (IR) injury, this study performed a proteomic analysis to qualitatively investigate such alterations resulting from acute glaucoma. The IR injury model combined with the proteomic analysis approach of two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to monitor the protein expression alterations in two groups of specimens (an IR injury group and a control group). The analysis results revealed 221 unique differentially expressed proteins of a total of 1481 proteins in the cornea between the two groups. In addition, 97 of 1206 conjunctival proteins, 90 of 1354 uveal proteins, 61 of 1180 scleral proteins, and 37 of 1204 retinal proteins were differentially expressed. These findings imply that different ocular tissues have different tolerances against IR injury. To sum up, this study utilized the acute glaucoma model combined with 2D-DIGE and MALDI-TOF MS to investigate the IR injury affected protein expression on various ocular tissues, and based on the ratio of protein expression alterations, the alterations in the ocular tissues were in the following order: the cornea, conjunctiva, uvea, sclera, and retina.

Creating a pyramidal structure on an n-GaN surface is considered the most effective approach for maximizing light extraction of n-side-up GaN-based light-emitting diodes (LEDs). This letter shows that the light extraction efficiency of a pyramidal n-GaN surface can be further enhanced by growing ZnO nano-rods (NRs) specifically on the tips of the pyramids on the n-GaN surface. Using tip-only ZnO NRs, the light-output power of an n-side-up LED with a pyramidal n-GaN surface can be further enhanced by 49.6% at 250 mA. This improved light extraction efficiency is due to the multiple facets on the ZnO NRs.

Drug resistance is one of the major causes of cancer chemotherapy failure. In the current study, we used a pair of lung adenocarcinoma cell lines, A549 and the pemetrexed-resistant A549/PEM cells, as a model to monitor resistance-dependent cellular responses and identify potential therapeutic targets. By means of 2D differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), we investigated the global protein expression alterations induced by pemetrexed treatment and resistance. The proteomic result revealed that pemetrexed exposure obviously altered the expression of 81 proteins in the A549 cells, whereas no significant response was observed in the similarly treated A549/PEM cells, hence implying an association between these proteins and the drug-specific response. Moreover, 72 proteins including flavin reductase and calreticulin demonstrated differential expression between the A549 and A549/PEM cells, indicating baseline resistance. Additional tests employed siRNA silencing, protein overexpression, cell viability analysis, and analysis of apoptosis to examine and confirm the potency of flavin reductase and calreticulin proteins in the development of pemetrexed resistance. In summary, by using a proteomic approach, we identified numerous proteins, including flavin reductase and calreticulin, involved in pemetrexed drug resistance-developing mechanisms. Our results provide useful diagnostic markers and therapeutic candidates for pemetrexed-resistant lung cancer treatment.

Background: Nontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. Methods: A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging examination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. Results: NONFH was diagnosed in 218 subjects (0.725%) and the estimated NONFH cases were 8.12 million among Chinese people aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females (1.02% vs. 0.51%, \(\chi^2\) = 24.997, P < 0.001). Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents (0.85% vs. 0.61%, \(\chi^2\) = 5.847, P = 0.016). Our multivariate regression analysis showed that high blood levels of triglycerides, total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head, heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. Conclusions: Our findings highlight that NONFH is a significant public health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.

To explore the effect of acupoint massage dominant early comprehensive intervention on the prognosis of premature infants with brain injury.Totally 210 premature infants with brain injury were assigned to the intervention group (112 cases) and the control group (98 cases). All patients received routine therapy (medicinal + routine care instructions). Patients in the intervention group additionally received acupoint massage. Those with abnormal early motion received physical sports treatment. Those with upper limbs dysfunction or with fine movement disorders received occupational therapy. Premature infants' development quotient (DQ) was performed at corrected age of 6 and 12 months by using neuropsychological development examination table for 0 - 6 years old children. The incidence of cerebral palsy was statistically calculated.At corrected age of 6 months, DQ of gross motor, fine motor, language three functional areas was higher in the intervention group than in the control group with significant difference (P0.05). At corrected age of 12 months, DQ of gross motor, fine motor, language, social and adaptive capacities was higher in the intervention group than in the control groupwith significant difference (P0.05). The incidence of cerebral palsy was 4.46% (5/112) in the intervention group and 12.24% (12/98) in the control group (P0.05).Acupoint massage dominant early comprehensive intervention could obviously improve the intelligence development level and lower the incidence of cerebral palsy in premature infants with brain injury.

// Shun-Hong Huang 1 , Ching-Hsuan Law 1 , Ping-Hsueh Kuo 2 , Ren-Yu Hu 1 , Ching-Chieh Yang 3, 4 , Ting-Wen Chung 1 , Ji-Min Li 1 , Li-Hsun Lin 1 , Yi-Chung Liu 1, 12 , En-Chi Liao 1 , Yi-Ting Tsai 1 , Yu-Shan Wei 1 , Chi-Chen Lin 5, 6, 7, 8 , Chien-Wen Chang 9 , Hsiu-Chuan Chou 10 , Wen-Ching Wang 2 , Margaret Dah-Tsyr Chang 2 , Lu-Hai Wang 11 , Hsing-Jien Kung 11 , Hong-Lin Chan 1, 2 , Ping-Chiang Lyu 1, 2 1 Department of Medical Sciences and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan 2 Department of Medical Sciences and Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan 3 Department of Radiation Oncology, Chi-Mei Medical Center, Tainan, Taiwan 4 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 5 Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan 6 Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan 7 Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan 8 Division of Chest Medicine. Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan 9 Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Taiwan 10 Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan 11 Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County, Taiwan 12 Institute of Population Sciences, National Health Research Institutes, Miaoli County, Taiwan Correspondence to: Hong-Lin Chan, e-mail: hlchan@life.nthu.edu.tw Ping-Chiang Lyu, e-mail: pclyu@mx.nthu.edu.tw Keywords: ECM, EMT, IF, MMP-13, OSCC Received: November 23, 2015 Accepted: February 09, 2016 Published: March 06, 2016 ABSTRACT The oral cancer cell line OC3-I5 with a highly invasive ability was selected and derived from an established OSCC line OC3. In this study, we demonstrated that matrix metalloproteinases protein MMP-13 was up-regulated in OC3-I5 than in OC3 cells. We also observed that expression of epithelial–mesenchymal transition (EMT) markers including Twist, p-Src, Snail1, SIP1, JAM-A, and vinculin were increased in OC3-I5 compared to OC3 cells, whereas E-cadherin expression was decreased in the OC3-I5 cells. Using siMMP-13 knockdown techniques, we showed that siMMP-13 not only reduced the invasion and migration, but also the adhesion abilities of oral cancer cells. In support of the role of MMP-13 in metastasis, we used MMP-13 expressing plasmid-transfected 293T cells to enhance MMP-13 expression in the OC3 cells, transplanting the MMP-13 over expressing OC3 cells into nude mice led to enhanced lung metastasis. In summary, our findings show that MMP-13 promotes invasion and metastasis in oral cancer cells, suggesting altered expression of MMP-13 may be utilized to impede the process of metastasis.