BioMed Research International The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Effect of Oral Coadministration of Ascorbic Acid with Ling Zhi Preparation on Pharmacokinetics of Ganoderic Acid A in Healthy Male Subjects: A Randomized Crossover Study Sun, 25 Sep 2016 14:24:02 +0000 The objective of this randomized, open-label, single-dose, two-phase crossover study was to determine the effect of ascorbic acid on pharmacokinetics of ganoderic acid A, an important biologically active triterpenoid compound with anticancer activities, following oral administration of water extract of fruiting bodies of Ling Zhi in 12 healthy male subjects. Each subject was randomized to receive either one of the two regimens: (1) a single dose of 3,000 mg of the Ling Zhi preparation or (2) a single dose of 3,000 mg of the Ling Zhi preparation in combination with 2,500 mg of ascorbic acid. After a washout period of at least two weeks, subjects were switched to receive the alternate regimen. Blood samples were collected in each phase immediately before dosing and at specific time points for 8 hours after dosing. Plasma ganoderic acid A concentrations were quantified using liquid chromatography-mass spectrometry (LC-MS). The pharmacokinetic parameters analyzed were maximal plasma concentration (), time to reach peak concentration (), area under the plasma concentration-time curve (), and half-life (). An oral coadministration of ascorbic acid with Ling Zhi preparation did not significantly alter the pharmacokinetic parameters of ganoderic acid A in healthy male subjects. Patcharanee Tawasri, Chadarat Ampasavate, Somsak Tharatha, Natthakarn Chiranthanut, and Supanimit Teekachunhatean Copyright © 2016 Patcharanee Tawasri et al. All rights reserved. Functional Roles of NOD1 in Odontoblasts on Dental Pulp Innate Immunity Sun, 25 Sep 2016 11:47:52 +0000 Caries-related pathogens are first recognized by odontoblasts and induce inflammatory events that develop to pulpitis. Generally, initial sensing of microbial pathogens is mediated by pattern recognition receptors, such as Toll-like receptor and nucleotide-binding oligomerization domain (NOD); however, little is known about NODs in odontoblasts. In this study, the levels of NODs expressed in rat odontoblastic cell line, KN-3, were assessed by flow cytometry and the levels of chemokines in NOD-specific ligand-stimulated KN-3 cells were analyzed by real-time PCR and ELISA. The signal transduction pathway activated with NOD-specific ligand was assessed by blocking assay with specific inhibitors and reporter assay. In KN-3 cells, the expression level of NOD1 was stronger than that of NOD2 and the production of chemokines, such as CINC-1, CINC-2, CCL20, and MCP-1, was upregulated by stimulation with NOD1-specific ligand, but not with NOD2-specific ligand. CINC-2 and CCL20 production by stimulation with NOD1-specific ligand was reduced by p38 MAPK and AP-1 signaling inhibitors. Furthermore, the reporter assay demonstrated AP-1 activation in NOD1-specific ligand-stimulated KN-3 cells. These findings indicated that NOD1 expressed in odontoblasts functions to upregulate the chemokines expression via p38-AP-1 signaling pathway and suggested that NOD1 may play important roles in the initiation and progression of pulpitis. Yuki Hosokawa, Kouji Hirao, Hiromichi Yumoto, Ayako Washio, Tadashi Nakanishi, Daisuke Takegawa, Chiaki Kitamura, and Takashi Matsuo Copyright © 2016 Yuki Hosokawa et al. All rights reserved. Two-Layer Tight Frame Sparsifying Model for Compressed Sensing Magnetic Resonance Imaging Sun, 25 Sep 2016 10:35:21 +0000 Compressed sensing magnetic resonance imaging (CSMRI) employs image sparsity to reconstruct MR images from incoherently undersampled -space data. Existing CSMRI approaches have exploited analysis transform, synthesis dictionary, and their variants to trigger image sparsity. Nevertheless, the accuracy, efficiency, or acceleration rate of existing CSMRI methods can still be improved due to either lack of adaptability, high complexity of the training, or insufficient sparsity promotion. To properly balance the three factors, this paper proposes a two-layer tight frame sparsifying (TRIMS) model for CSMRI by sparsifying the image with a product of a fixed tight frame and an adaptively learned tight frame. The two-layer sparsifying and adaptive learning nature of TRIMS has enabled accurate MR reconstruction from highly undersampled data with efficiency. To solve the reconstruction problem, a three-level Bregman numerical algorithm is developed. The proposed approach has been compared to three state-of-the-art methods over scanned physical phantom and in vivo MR datasets and encouraging performances have been achieved. Shanshan Wang, Jianbo Liu, Xi Peng, Pei Dong, Qiegen Liu, and Dong Liang Copyright © 2016 Shanshan Wang et al. All rights reserved. Use of Plant Extracts as an Effective Manner to Control Clostridium perfringens Induced Necrotic Enteritis in Poultry Sun, 25 Sep 2016 09:00:30 +0000 Necrotic enteritis (NE) is an important concern in poultry industry since it causes economic losses, increased mortality, reduction of bird welfare, and contamination of chicken products for human consumption. For decades, the use of in-feed antimicrobial growth promoters (AGPs) has been the main strategy to control intestinal pathogens including Clostridium perfringens (CP), the causative agent of NE. However, the use of AGPs in animal diet has been linked to the emergence and transmission of antimicrobial resistance through food-borne microorganisms, which has led to the ban of AGPs in many countries. This scenario has challenged the poultry industry to search for safer alternative products in order to prevent NE. In this context, the utilization of natural plant extracts with antimicrobial properties appears as a promising and feasible tool to control NE in chicken. In this paper, we review the scientific studies analyzing the potential of plant extracts as alternative feed additives to reduce NE in poultry, with focus on two types of plant products that arise as promising candidates: tannins and essential oils. Some of these products showed antimicrobial activity against CP and coccidia in vitro and in vivo and are able to increase productive performance, emulating the bioactive properties of AGPs. J. M. Diaz Carrasco, L. M. Redondo, E. A. Redondo, J. E. Dominguez, A. P. Chacana, and M. E. Fernandez Miyakawa Copyright © 2016 J. M. Diaz Carrasco et al. All rights reserved. Structural and Histochemical Alterations in the Aortic Valves of Elderly Patients: A Comparative Study of Aortic Stenosis, Aortic Regurgitation, and Normal Valves Sun, 25 Sep 2016 08:17:32 +0000 The aim of this study was to reveal the pathogenesis of aortic stenosis (AS) and regurgitation (AR) by comparing differences in mechanical and biochemical alterations. We applied scanning acoustic microscopy (SAM) to measure the speed of sound (SOS) through valves to estimate the elasticity and monitor sensitivity to protease treatment, as the SOS is correlated with the stiffness of materials, which is reduced after digestion by proteases. The fibrosa of both the AS and AR groups were stiffer than the fibrosa of the normal group. The AR group displayed significantly stiffer fibrosa than the AS group, with the exception of calcified areas. The AS group showed significantly decreased SOS values following protease digestion, whereas the AR showed little reduction. The AS group presented type III collagen in the fibrosa and the ventricularis. In the AR group, both type I collagen and type III collagen coexisted in the fibrosa and the ventricularis. Upon immunostaining for advanced glycation end-products, the AS group showed sparse, weak staining, whereas the AR group presented a strong, band-like positive reaction in the fibrosa. In conclusion, tissue remodelling associated with damage and repair is associated with AS pathogenesis, whereas static chemical alterations with slow collagen turnover induce AR. Katsutoshi Miura and Hideki Katoh Copyright © 2016 Katsutoshi Miura and Hideki Katoh. All rights reserved. Black Currant (Ribes nigrum L.) and Bilberry (Vaccinium myrtillus L.) Fruit Juices Inhibit Adhesion of Asaia spp. Sun, 25 Sep 2016 08:17:11 +0000 The aim of the study was to evaluate the activity of high-polyphenolic black currant (Ribes nigrum L.) and bilberry (Vaccinium myrtillus L.) juices against bacterial strains Asaia lannensis and Asaia bogorensis isolated as spoilage of commercial soft drinks. The composition of fruit juices was evaluated using chromatographic techniques HPLC and LC-MS. The adhesion to glass, polystyrene, and polyethylene terephthalate in two different culture media was evaluated by luminometry and the plate count method. The major anthocyanins in the V. myrtillus were petunidin-3-glucoside, malvidin-3-glucoside, cyanidin-3-glucoside, and delphinidin-3-glucoside, while in R. nigrum delphinidin-3-rutinoside and cyanidin-3-rutinoside were detected. The LC-MS analysis showed presence of anthocyanins (delphinidin, cyanidin, petunidin, and malvidin derivatives), phenolic acids (chlorogenic and neochlorogenic acids), flavonols (quercetin-3-glucoside, quercetin-3-rutinoside), and flavanols (procyanidin B2 and procyanidin type A2). Additionally, in the bilberry juice A type procyanidin trimer was detected. The adhesion of Asaia spp. cells depended on the type of medium, carbon sources, and the type of abiotic surfaces. We noted that the adhesion was significantly stronger in minimal medium containing sucrose. The addition of bilberry and black currant juices notably reduced bacterial growth as well as cell adhesion to polyethylene terephthalate surfaces. Hubert Antolak, Agata Czyzowska, and Dorota Kregiel Copyright © 2016 Hubert Antolak et al. All rights reserved. Effect of Phosphatase and Tensin Homologue on Chromosome 10 on Angiotensin II-Mediated Proliferation, Collagen Synthesis, and Akt/P27 Signaling in Neonatal Rat Cardiac Fibroblasts Sun, 25 Sep 2016 07:16:45 +0000 Cardiac fibroblasts (CFs) play a key role in cardiac fibrosis by regulating the balance between extracellular matrix synthesis and breakdown. Although phosphatase and tensin homologue on chromosome 10 (PTEN) has been found to play an important role in cardiovascular disease, it is not clear whether PTEN is involved in functional regulation of CFs. In the present study, PTEN was overexpressed in neonatal rat CFs via recombinant adenovirus-mediated gene transfer. The effects of PTEN overexpression on cell-cycle progression and angiotensin II- (Ang II-) mediated regulation of collagen metabolism, synthesis of matrix metalloproteinases, and Akt/P27 signaling were investigated. Compared with uninfected cells and cells infected with green fluorescent protein-expressing adenovirus (Ad-GFP), cells infected with PTEN-expressing adenovirus (Ad-PTEN) significantly increased PTEN protein and mRNA levels in CFs (). The proportion of CFs in the G1/S cell-cycle phase was significantly higher for PTEN-overexpressing cells. In addition, Ad-PTEN decreased mRNA expression and the protein synthesis rate of collagen types I and III and antagonized Ang II-induced collagen synthesis. Overexpression of PTEN also decreased Ang II-induced matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) production as well as gelatinase activity. Moreover, Ad-PTEN decreased Akt expression and increased P27 expression independent of Ang II stimulation. These results suggest that PTEN could regulate its functional effects in neonatal rat CFs partially via the Akt/P27 signaling pathway. Ling Nie, Jing-Hong Zhao, Jiang Wang, Rong Song, and Shan-Jun Zhu Copyright © 2016 Ling Nie et al. All rights reserved. The Effect of Kanamycin and Tetracycline on Growth and Photosynthetic Activity of Two Chlorophyte Algae Sun, 25 Sep 2016 07:12:01 +0000 Antibiotics are routinely used in microalgae culture screening, stock culture maintenance, and genetic transformation. By studying the effect of antibiotics on microalgae growth, we can estimate the least value to inhibit growth of undesired pathogens in algal culture. We studied the effect of kanamycin and tetracycline on the growth and photosynthetic activity of two chlorophyte microalgae, Dictyosphaerium pulchellum and Micractinium pusillum. We measured CFU mL−1 on agar plates, optical density, fluorescence yields, and photosynthetic inhibition. Our results showed a significant effect of kan and tet on the tested microalgae species except tet, which showed a minor effect on M. pusillum. Both antibiotics are believed to interact with the protein synthesis machinery; hence, the inhibitory effect of the tested antibiotics was further confirmed by isolation and quantification of the whole cell protein. A significant reduction in protein quantity was observed at concentrations more than 5 mg L−1, except M. pusillum, which showed only a slight reduction in protein quantity even at the maximum tested concentration of tet (30 mg L−1). This study can further aid in aquaculture industry, for the maintenance of the microalgae stock cultures and it can also help the microalgae genetic engineers in the construction of molecular markers. Khawaja Muhammad Imran Bashir and Man-Gi Cho Copyright © 2016 Khawaja Muhammad Imran Bashir and Man-Gi Cho. All rights reserved. C3a Increases VEGF and Decreases PEDF mRNA Levels in Human Retinal Pigment Epithelial Cells Thu, 22 Sep 2016 16:16:00 +0000 Complement activation, specifically complement 3 (C3) activation and C3a generation, contributes to an imbalance between angiogenic stimulation by vascular endothelial growth factor (VEGF) and angiogenic inhibition by pigment epithelial derived factor (PEDF), leading to pathological angiogenesis. This study aimed to investigate the effects of C3a and small interfering RNA (siRNA) targeting C3 on the levels of VEGF and PEDF mRNAs in human retinal pigment epithelial (RPE) cells. ARPE-19 cells were cultured in the presence of exogenous C3a at 0.1 μM and 0.3 μM C3a for 24, 48, and 72 hours. 0.1 pmol/μL duplexes of siRNA targeting C3 were applied for C3a inhibition by transfecting ARPE-19 cells for 48 hours. RT-PCR was performed to examine the level of VEGF and PEDF mRNA. A random siRNA duplex was set for control siRNA. Results demonstrated that exogenous C3a significantly upregulated VEGF and downregulated PEDF mRNA levels in cultured ARPE-19 cells, and siRNA targeting C3 transfection reversed the above changes, significantly reducing VEGF and enhancing PEDF mRNAs level in ARPE-19 cells compared to the control. The present data provided evidence that reducing C3 activation can decreases VEGF and increase PEDF mRNA level in RPE and may serve as a potential therapy in pathological angiogenesis. Qin Long, Xiaoguang Cao, Ailing Bian, and Ying Li Copyright © 2016 Qin Long et al. All rights reserved. Sacro-Iliac Joint Sensory Block and Radiofrequency Ablation: Assessment of Bony Landmarks Relevant for Image-Guided Procedures Thu, 22 Sep 2016 16:08:38 +0000 Image-guided sensory block and radiofrequency ablation of the nerves innervating the sacro-iliac joint require readily identifiable bony landmarks for accurate needle/electrode placement. Understanding the relative locations of the transverse sacral tubercles along the lateral sacral crest is important for ultrasound guidance, as they demarcate the position of the posterior sacral network (S1–S3 ± L5/S4) innervating the posterior sacro-iliac joint. No studies were found that investigated the spatial relationships of these bony landmarks. The purpose of this study was to visualize and quantify the interrelationships of the transverse sacral tubercles and posterior sacral foramina to inform image-guided block and radiofrequency ablation of the sacro-iliac joint. The posterior and lateral surfaces of 30 dry sacra (15 M/15 F) were digitized and modeled in 3D and the distances between bony landmarks quantified. The relationships of bony landmarks (S1–S4) were not uniform. The mean intertubercular and interforaminal distances decreased from S1 to S4, whereas the distance from the lateral margin of the posterior sacral foramina to the transverse sacral tubercles increased from S1 to S3. The mean intertubercular distance from S1 to S3 was significantly () larger in males. The interrelationships of the sacral bony landmarks should be taken into consideration when estimating the site and length of an image-guided strip lesion targeting the posterior sacral network. Trevor J. G. Robinson, Shannon L. Roberts, Robert S. Burnham, Eldon Loh, and Anne M. Agur Copyright © 2016 Trevor J. G. Robinson et al. All rights reserved. Bonding of Metal Orthodontic Attachments to Sandblasted Porcelain and Zirconia Surfaces Thu, 22 Sep 2016 13:34:39 +0000 This study evaluates tensile bond strength (TBS) of metal orthodontic attachments to sandblasted feldspathic porcelain and zirconia with various bonding protocols. Thirty-six (36) feldspathic and 36 zirconia disc samples were prepared, glazed, embedded in acrylic blocks and sandblasted, and divided into three groups according to one or more of the following treatments: hydrofluoric acid 4% (HF), Porcelain Conditioner silane primer, Reliance Assure® primer, Reliance Assure plus® primer, and Z Prime™ plus zirconia primer. A round traction hook was bonded to each sample. Static tensile bond strength tests were performed in a universal testing machine and adhesive remnant index (ARI) scoring was done using a digital camera. One-way ANOVA and Pearson chi-square tests were used to analyze TBS (MPa) and ARI scores. No statistically significant mean differences were found in TBS among the different bonding protocols for feldspathic and zirconia, values = 0.369 and 0.944, respectively. No statistically significant distribution of ARI scores was found among the levels of feldspathic, value = 0.569. However, statistically significant distribution of ARI scores was found among the levels of zirconia, value = 0.026. The study concluded that silanization following sandblasting resulted in tensile bond strengths comparable to other bonding protocols for feldspathic and zirconia surface. Amitoj S. Mehta, Carla A. Evans, Grace Viana, Ana Bedran-Russo, and Maria Therese S. Galang-Boquiren Copyright © 2016 Amitoj S. Mehta et al. All rights reserved. The Role of Interleukin-18 in Serum and Follicular Fluid during In Vitro Fertilization and Intracytoplasmic Sperm Injection Thu, 22 Sep 2016 13:18:15 +0000 Cytokines are key modulators of the immune system and play an important role in the ovarian cycle. IL-18 levels in serum and follicular fluid were analyzed in women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. The cohort study group consisted of 90 women, who were undergoing IVF or ICSI. The body mass index (BMI) was determined in all patients; IL-18 levels were measured in follicular fluid and serum. IL-18 levels in serum were significantly higher than those in follicular fluid. The median level in serum was 162.75 (80.21) pg/mL and that in follicular fluid, 138.24 (91.78) pg/mL. Women undergoing IVF treatment had lower IL-18 levels in serum (median, 151.19 (90.73) pg/mL) than those treated with ICSI (median, 163.57 (89.97) pg/mL). The correlation between IL-18 levels in serum and BMI was statistically significant, as well as the correlation between IL-18 levels in follicular fluid and ovarian stimulation response (). IL-18 was correlated with the response to ovarian stimulation and was the reason for successful pregnancy after IVF or ICSI treatment. Among other cytokines, IL-18 appears to be a promising prognostic marker of success in reproductive treatment and should be evaluated as such in further prospective studies. Veronika Günther, Ibrahim Alkatout, Corinna Fuhs, Ali Salmassi, Liselotte Mettler, Jürgen Hedderich, Nicolai Maass, Mohamed Elessawy, Andreas Gerd Schmutzler, and Christel Eckmann-Scholz Copyright © 2016 Veronika Günther et al. All rights reserved. Adult Onset Vitiligo: Multivariate Analysis Suggests the Need for a Thyroid Screening Thu, 22 Sep 2016 10:29:38 +0000 Background. There are limited epidemiological studies evaluating the effect of age at onset on disease features in vitiligo. Objectives. To identify factors associated with adult onset vitiligo in comparison with childhood onset vitiligo. Patients and Methods. We retrospectively collected medical records of 191 patients. Such records included clinical examination, personal and familial medical history, laboratory evaluations, concomitant vitiligo treatment and drug assumption. Results. 123 patients with a disease onset after the age of 40 (adult onset vitiligo) were compared with 68 patients who developed vitiligo before the age of 12 (childhood onset vitiligo). Multivariate analysis revealed that personal history of thyroid diseases (; OR 0.4), stress at onset (; OR = 0.34), personal history of autoimmune thyroid disease (ATD) (; OR = 0.23), and thyroid nodules (; OR 0.90) were independently associated with adult onset vitiligo, whereas family history of dermatological diseases (; OR = 2.87) and Koebner phenomenon (; OR = 4.73) with childhood onset vitiligo. Moreover, in the adult onset group, concomitant thyroid disease preceded vitiligo in a statistically significant number of patients (). Conclusions. Childhood onset and adult onset vitiligo have different clinical features. In particular, ATD and thyroid nodules were significantly associated with adult onset vitiligo, suggesting that a thyroid screening should be recommended in this group of patients. L. Lazzeri, R. Colucci, A. Cammi, F. Dragoni, and S. Moretti Copyright © 2016 L. Lazzeri et al. All rights reserved. Audiovestibular Function Deficits in Vestibular Schwannoma Thu, 22 Sep 2016 09:26:39 +0000 Introduction. Vestibular schwannomas (VS) are benign tumours of the vestibular nerve and can lead to hearing loss, tinnitus, vertigo, facial palsy, and brainstem compression. Audiovestibular diagnostic tests are essential for detection and treatment planning. Methods. Medline was used to perform a systematic literature review with regard to how audiovestibular test parameters correlate with symptoms, tumour size, and tumour location. Results. The auditory brainstem response can be used to diagnose retrocochlear lesions caused by VS. Since hearing loss correlates poorly with tumour size, a retrocochlear lesion is probably not the only cause for hearing loss. Also cochlear mechanisms seem to play a role. This can be revealed by abnormal otoacoustic emissions, despite normal ABR and new MRI techniques which have demonstrated endolymphatic hydrops of the inner ear. Caloric and head impulse tests show frequency specific dynamics and vestibular evoked myogenic potentials may help to identify the location of the tumour regarding the involved nerve parts. Conclusion. In order to preserve audiovestibular function in VS, it is important to stop the growth of the tumour and to avoid degenerative changes in the inner ear. A detailed neurotological workup helps to diagnose VS of all sizes and can also provide useful prognostic information. Constantin von Kirschbaum and Robert Gürkov Copyright © 2016 Constantin von Kirschbaum and Robert Gürkov. All rights reserved. Role of Cilostazol Therapy in Hemodialysis Patients with Asymptomatic Peripheral Arterial Disease: A Retrospective Cohort Study Thu, 22 Sep 2016 09:01:29 +0000 Background. Peripheral arterial disease (PAD) and its relevant complications are more common in hemodialysis (HD) patients, while the evidence regarding antiplatelet therapy in CKD patients is scarce. We retrospectively analyzed the efficacy of cilostazol on outcomes in HD patients with asymptomatic PAD (aPAD). Methods. This cohort study enrolled 217 HD patients (median follow-up time: 5.75 years). Associations between cilostazol use and the outcomes were evaluated by time-dependent Cox regression analysis. Results. During follow-up, 39.5% (47/119) patients used cilostazol for aPAD and 31.8% (69/217) patients died. Cilostazol users had significantly lower CVD and all-cause mortalities (adjusted HR [95% CI]: 0.11 [0.03, 0.51] and 0.2 [0.08, 0.52]) than nonusers. Both death risks were nonsignificantly higher in cilostazol users than in HD patients without aPAD. The unadjusted and adjusted HR [95% CI] of CVD death risk were 0.4 [0.07, 2.12] and 0.14 [0.02, 0.8] for patients with aPAD during follow-up and were 0.74 [0.16, 3.36] and 0.19 [0.04, 0.93] for those with aPAD at initial. Conclusions. In HD patients with aPAD, lower CVD and all-cause mortality rates were observed in low-dose cilostazol user. Further evidences from large-scale prospective study and randomization trial are desired to confirm the effect of cilostazol. Paik Seong Lim, Yachung Jeng, Ming Ying Wu, Mei-Ann Pai, Tsai-Kun Wu, and Chang Hsu Chen Copyright © 2016 Paik Seong Lim et al. All rights reserved. Long Noncoding RNA H19 in Digestive System Cancers: A Meta-Analysis of Its Association with Pathological Features Wed, 21 Sep 2016 14:31:55 +0000 Long noncoding RNA (lncRNA) H19 has been reported to be upregulated in malignant digestive tumors, but its clinical relevance is not yet established. The meta-analysis was to investigate the association between H19 expression and pathological features of digestive system cancers. The databases of PubMed, EMBase, Web of Science, CNKI, and WanFang were searched for the related studies. A total of 478 patients from 6 studies were finally included. The meta-analysis showed that the patient group of high H19 expression had a higher risk of poorly differentiated grade, deep tumor invasion (T2 stage or more), lymph node metastasis, and advanced TNM stage than the group of low H19 expression, although there was no difference between them in terms of distant metastasis. Therefore, the high expression of lncRNA H19 might predict poor oncological outcomes of patients with digestive system cancers. Yang Lin, Lijian Xu, Wei Wei, Xiaohui Zhang, and Rongchao Ying Copyright © 2016 Yang Lin et al. All rights reserved. Activated Müller Cells Involved in ATP-Induced Upregulation of P2X7 Receptor Expression and Retinal Ganglion Cell Death Wed, 21 Sep 2016 13:55:44 +0000 P2X7 receptor (P2X7R), an ATP-gated ion channel, plays an important role in glaucomatous retinal ganglion cell (RGC) apoptotic death, in which activated retinal Müller glial cells may be involved by releasing ATP. In the present study, we investigated whether and how activated Müller cells may induce changes in P2X7R expression in RGCs by using immunohistochemistry and Western blot techniques. Intravitreal injection of DHPG, a group I metabotropic glutamate receptor (mGluR I) agonist, induced upregulation of GFAP expression, suggestive of Müller cell activation (gliosis), as we previously reported. Accompanying Müller cell activation, P2X7R protein expression was upregulated, especially in the cells of ganglion cell layer (GCL), which was reversed by coinjection of brilliant blue G (BBG), a P2X7R blocker. In addition, intravitreal injection of ATP also induced upregulation of P2X7R protein expression. Similar results were observed in cultured retinal neurons by ATP treatment. Moreover, both DHPG and ATP intravitreal injection induced a reduction in the number of fluorogold retrogradely labeled RGCs, and the DHPG effect was partially rescued by coinjection of BBG. All these results suggest that activated Müller cells may release ATP and, in turn, induce upregulation of P2X7R expression in the cells of GCL, thus contributing to RGC death. Ying Xue, Yuting Xie, Bo Xue, Nan Hu, Guowei Zhang, Huaijin Guan, and Min Ji Copyright © 2016 Ying Xue et al. All rights reserved. The -174G/C Interleukin-6 Gene Promoter Polymorphism as a Genetic Marker of Differences in Therapeutic Response to Methotrexate and Leflunomide in Rheumatoid Arthritis Wed, 21 Sep 2016 12:18:12 +0000 Objective. To evaluate the association of -174G/C IL-6 polymorphism with failure in therapeutic response to methotrexate (MTX) or leflunomide (LEF). This prospective, observational cohort included 96 Mexican-Mestizo patients with moderate or severe rheumatoid arthritis (RA), initiating MTX or LEF, genotyped for IL-6 -174G/C polymorphism by PCR-RFLP. Therapeutic response was strictly defined: only if patients achieved remission or low disease activity (DAS-28 < 3.2). Results. Patients with MTX or LEF had significant decrement in DAS-28 (); nevertheless, only 14% and 12.5% achieved DAS-28 < 3.2 at 3 and 6 months. After 6 months with any of these drugs the -174G/G genotype carriers (56%) had higher risk of therapeutic failure compared with GC (RR: 1.19, 95% CI: 1.07–1.56). By analyzing each drug separately, after 6 months with LEF, GG genotype confers higher risk of therapeutic failure than GC (RR = 1.56; 95% CI = 1.05–2.3; ), or CC (RR = 1.83; 95% CI = 1.07–3.14; ). This risk was also observed in the dominant model (RR = 1.33; 95% CI = 1.03–1.72; ). Instead, in patients receiving MTX no genotype was predictor of therapeutic failure. We concluded that IL-6 -174G/G genotype confers higher risk of failure in therapeutic response to LEF in Mexicans and if confirmed in other populations this can be used as promissory genetic marker to differentiate risk of therapeutic failure to LEF. A. J. Ruiz-Padilla, J. I. Gamez-Nava, A. M. Saldaña-Cruz, J. D. Murillo-Vazquez, M. L. Vazquez-Villegas, S. A. Zavaleta-Muñiz, B. T. Martín-Márquez, J. M. Ponce-Guarneros, N. A. Rodriguez Jimenez, A. Flores-Chavez, F. Sandoval-Garcia, J. C. Vasquez-Jimenez, E. G. Cardona-Muñoz, S. E. Totsuka-Sutto, and L. Gonzalez-Lopez Copyright © 2016 A. J. Ruiz-Padilla et al. All rights reserved. Shear Bond Strength of Three Orthodontic Bonding Systems on Enamel and Restorative Materials Wed, 21 Sep 2016 12:17:13 +0000 Objective. The aim of this in vitro study was to determine the shear bond strength (SBS) and adhesive remnant index (ARI) score of two self-etching no-mix adhesives (iBond™ and Scotchbond™) on different prosthetic surfaces and enamel, in comparison with the commonly used total etch system Transbond XT™. Materials and Methods. A total of 270 surfaces (1 enamel and 8 restorative surfaces, ) were randomly divided into three adhesive groups. In group 1 (control) brackets were bonded with Transbond XT primer. In the experimental groups iBond adhesive (group 2) and Scotchbond Universal adhesive (group 3) were used. The SBS was measured using a Zwicki 1120™ testing machine. The ARI and SBS were compared statistically using the Kruskal–Wallis test (). Results. Significant differences in SBS and ARI were found between the control group and experimental groups. Conclusions. Transbond XT showed the highest SBS on human enamel. Scotchbond Universal on average provides the best bonding on all other types of surface (metal, composite, and porcelain), with no need for additional primers. It might therefore be helpful for simplifying bonding in orthodontic procedures on restorative materials in patients. If metal brackets have to be bonded to a metal surface, the use of a dual-curing resin is recommended. Andreas Hellak, Jennifer Ebeling, Michael Schauseil, Steffen Stein, Matthias Roggendorf, and Heike Korbmacher-Steiner Copyright © 2016 Andreas Hellak et al. All rights reserved. Using Innovative Acoustic Analysis to Predict the Postoperative Outcomes of Unilateral Vocal Fold Paralysis Wed, 21 Sep 2016 11:24:50 +0000 Objective. Autologous fat injection laryngoplasty is ineffective for some patients with iatrogenic vocal fold paralysis, and additional laryngeal framework surgery is often required. An acoustically measurable outcome predictor for lipoinjection laryngoplasty would assist phonosurgeons in formulating treatment strategies. Methods. Seventeen thyroid surgery patients with unilateral vocal fold paralysis participated in this study. All subjects underwent lipoinjection laryngoplasty to treat postsurgery vocal hoarseness. After treatment, patients were assigned to success and failure groups on the basis of voice improvement. Linear prediction analysis was used to construct a new voice quality indicator, the number of irregular peaks (NIrrP). It compared with the measures used in the Multi-Dimensional Voice Program (MDVP), such as jitter (frequency perturbation) and shimmer (perturbation of amplitude). Results. By comparing the [i] vowel produced by patients before the lipoinjection laryngoplasty (AUC = 0.98, 95% CI = 0.78–0.99), NIrrP was shown to be a more accurate predictor of long-term surgical outcomes than jitter (AUC = 0.73, 95% CI = 0.47–0.91) and shimmer (AUC = 0.63, 95% CI = 0.37–0.85), as identified by the receiver operating characteristic curve. Conclusions. NIrrP measured using the LP model could be a more accurate outcome predictor than the parameters used in the MDVP. Yung-An Tsou, Yi-Wen Liu, Wen-Dien Chang, Wei-Chen Chen, Hsiang-Chun Ke, Wen-Yang Lin, Hsing-Rong Yang, Dung-Yun Shie, and Ming-Hsui Tsai Copyright © 2016 Yung-An Tsou et al. All rights reserved. Radiation-Guided Peptide Delivery in a Mouse Model of Nasopharyngeal Carcinoma Wed, 21 Sep 2016 10:58:34 +0000 Purpose. This study aimed to evaluate the characteristics of the HVGGSSV peptide, exploring radiation-guided delivery in a mouse model of nasopharyngeal carcinoma. Methods. Mice with CNE-1 nasopharyngeal carcinoma were assigned to two different groups treated with Cy7-NHS and Cy7-HVGGSSV, respectively. Meanwhile, each mouse received a single dose of 3 Gy radiation. Biological distribution of the recombinant peptide was assessed on an in vivo small animal imaging system. Results. The experimental group showed maximum fluorescence intensity in irradiated tumors treated with Cy7-labeled HVGGSSV, while untreated (0 Gy) control tumors showed lower intensity levels. Fluorescence intensities of tumors in the right hind limbs of experimental animals were , , , , and photons/s/cm2 higher compared with left hind limb values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence intensities of tumor in the right hind limbs of the experimental group were , , , , and photons/s/cm2 higher compared with control group values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence was not specifically distributed in the control group. Compared with low fluorescence intensity in the heart, lungs, and tumors, high fluorescence distribution was found in the liver and kidney at 48 h. Conclusions. HVGGSSV was selectively bound to irradiated nasopharyngeal carcinoma, acting as a targeting transport carrier for radiation-guided drugs that are mainly metabolized in the kidney and liver. Pei-cheng Lin, Jun-yan He, Yu-yin Le, Kai-xin Du, Wei-feng Zhu, Qing-qin Peng, Ya-ping Dong, Jin-luan Li, and Jun-xin Wu Copyright © 2016 Pei-cheng Lin et al. All rights reserved. Alkaline Pretreatment of Sugarcane Bagasse and Filter Mud Codigested to Improve Biomethane Production Wed, 21 Sep 2016 08:27:43 +0000 To enhance the codigestion of degradation and improve biomethane production potential, sugarcane bagasse and filter mud were pretreated by sodium hydroxide NaOH 1 N at 100°C for 15, 30, and 45 minutes, respectively. Biomethane generation from 1-liter batch reactor was studied at mesophilic temperature ()°C, solid concentrations of 6%, and five levels of mixing proportion with and without pretreatment. The results demonstrate that codigestion of filter mud with bagasse produces more biomethane than fermentation of filter mud as single substrate; even codigested substrate composition presented a better balance of nutrients (C/N ratio of 24.70) when codigestion ratio between filter mud and bagasse was 25 : 75 in comparison to filter mud as single substrate (C/N ratio 9.68). All the pretreatments tested led to solubilization of the organic matter, with a maximum lignin reduction of 86.27% and cumulative yield of biomethane (195.8 mL·g, digestion of pretreated bagasse as single substrate) obtained after 45 minutes of cooking by NaOH 1 N at 100°C. Under this pretreatment condition, significant increase in cumulative methane yield was observed (126.2 mL·g) at codigestion ratio of 25 : 75 between filter mud and bagasse by increase of 81.20% from untreated composition. Zahir Talha, Weimin Ding, Esmaeil Mehryar, Muhammad Hassan, and Jinhua Bi Copyright © 2016 Zahir Talha et al. All rights reserved. Exercise Alters Gait Pattern but Not Knee Load in Patients with Knee Osteoarthritis Tue, 20 Sep 2016 16:47:54 +0000 Six female patients with bilateral medial knee OA and 6 healthy controls were recruited. Patients with knee OA received a 6-week physiotherapist-supervised and home-based exercise program. Outcome measures, including the Western Ontario and McMaster Universities Arthritis Index and Short Form-36 Health Survey as well as objective biomechanical indices were obtained at baseline and follow-up. After treatment, no significant difference was observed in the knee abductor moment (KAM), lever arm, and ground reaction force. We, however, observed significantly improved pain and physical function as well as altered gait patterns, including a higher hip flexor moment and hip extension angle with a faster walking speed. Although KAM was unchanged, patients with bilateral knee OA showed an improved walking speed and altered the gait pattern after 6 weeks of supervised exercise. This finding suggests that the exercise intervention improves proximal joint mechanics during walking and can be considered for patients with bilateral knee OA. Non-weight-bearing strengthening without external resistance combined with stretching exercise may be an option to improve pain and function in individuals with OA who cannot perform high resistance exercises owing to pain or other reasons. Ssu-Yu Chang, Yi-Jia Lin, Wei-Chun Hsu, Lin-Fen Hsieh, Yuan-Hsiang Lin, Chao-Chin Chang, You-Cai Chou, and Li-Fei Chen Copyright © 2016 Ssu-Yu Chang et al. All rights reserved. Optimized Collection Protocol for Plasma MicroRNA Measurement in Patients with Cardiovascular Disease Tue, 20 Sep 2016 16:39:51 +0000 Background. Various microRNAs (miRNAs) are used as markers of acute coronary syndrome, in which heparinization is considered mandatory therapy. Nevertheless, a standard method of handling plasma samples has not been proposed, and the effects of heparin treatment on miRNA detection are rarely discussed. Materials and Method. This study used quantitative polymerase chain reaction (qPCR) analysis to investigate how storage temperature, standby time, hemolysis, and heparin treatment affect miRNA measurement in plasma samples from 25 patients undergoing cardiac catheterization. Results. For most miRNAs, the qPCR results remained consistent during the first 2 hours. The miRNA signals did not significantly differ between samples stored at 4°C before processing and samples stored at room temperature (RT) before processing. miR-451a/miR-23a ratio < 60 indicated < 0.12% hemolysis with 100% sensitivity and 100% specificity. Pretreatment with 0.25 U heparinase I recovered qPCR signals that were reduced by in vivo heparinization. Conclusions. For miRNA measurement, blood samples stored at RT should be processed into plasma within 2 hours after withdrawal and should be pretreated with 0.25 U heparinase I to overcome heparin-attenuated miRNA signals. The miR-451a/miR-23a ratio is a reliable indicator of significant hemolysis. Chi-Sheng Wu, Fen-Chiung Lin, Shu-Jen Chen, Yung-Lung Chen, Wen-Jung Chung, and Cheng-I Cheng Copyright © 2016 Chi-Sheng Wu et al. All rights reserved. Effect of Removal of Enamel on Rebonding Strength of Resin Composite to Enamel Tue, 20 Sep 2016 16:36:59 +0000 Objective. To examine the effect of removing the surface layer of enamel on the rebonding strength of resin composite. Methods. Teeth in four groups () were etched, a small amount of resin composite was bonded and debonded, then specimens in three groups were ground for different lengths of time (10 s, 20 s, 30 s) to remove an increasing amount of enamel, one group was left untouched. The teeth were bonded again and the bond strengths of 1st and 2nd bonding were compared and analysed against the amount of enamel loss in different groups (7 µm (±2); 12 µm (±1); 16 µm (±3)). Specimens were examined with SEM and by noncontacting optical profilometer. Results. Although results indicated higher rebonding strength with increasing enamel removal ANOVA showed low statistical differences between the groups (). However, values between first bonding and rebonding strengths differed significantly () in the group that was not ground. SEM revealed that enamel-surfaces that were ground after debonding etched well, compared to the surfaces that still contained adhesive remnants. Conclusions. Removal of small amount of enamel refreshed the surface for rebonding. Rebonding strengths without grinding the surface before bonding were lower than bond strength to intact enamel. L. Kilponen, L. Lassila, M. Tolvanen, J. Varrela, and P. K. Vallittu Copyright © 2016 L. Kilponen et al. All rights reserved. Smoothed Norm Regularization for Sparse-View X-Ray CT Reconstruction Tue, 20 Sep 2016 16:36:47 +0000 Low-dose computed tomography (CT) reconstruction is a challenging problem in medical imaging. To complement the standard filtered back-projection (FBP) reconstruction, sparse regularization reconstruction gains more and more research attention, as it promises to reduce radiation dose, suppress artifacts, and improve noise properties. In this work, we present an iterative reconstruction approach using improved smoothed (SL0) norm regularization which is used to approximate norm by a family of continuous functions to fully exploit the sparseness of the image gradient. Due to the excellent sparse representation of the reconstruction signal, the desired tissue details are preserved in the resulting images. To evaluate the performance of the proposed SL0 regularization method, we reconstruct the simulated dataset acquired from the Shepp-Logan phantom and clinical head slice image. Additional experimental verification is also performed with two real datasets from scanned animal experiment. Compared to the referenced FBP reconstruction and the total variation (TV) regularization reconstruction, the results clearly reveal that the presented method has characteristic strengths. In particular, it improves reconstruction quality via reducing noise while preserving anatomical features. Ming Li, Cheng Zhang, Chengtao Peng, Yihui Guan, Pin Xu, Mingshan Sun, and Jian Zheng Copyright © 2016 Ming Li et al. All rights reserved. Advances in Engineered Liver Models for Investigating Drug-Induced Liver Injury Tue, 20 Sep 2016 16:36:17 +0000 Drug-induced liver injury (DILI) is a major cause of drug attrition. Testing drugs on human liver models is essential to mitigate the risk of clinical DILI since animal studies do not always suffice due to species-specific differences in liver pathways. While primary human hepatocytes (PHHs) can be cultured on extracellular matrix proteins, a rapid decline in functions leads to low sensitivity (<50%) in DILI prediction. Semiconductor-driven engineering tools now allow precise control over the hepatocyte microenvironment to enhance and stabilize phenotypic functions. The latest platforms coculture PHHs with stromal cells to achieve hepatic stability and enable crosstalk between the various liver cell types towards capturing complex cellular mechanisms in DILI. The recent introduction of induced pluripotent stem cell-derived human hepatocyte-like cells can potentially allow a better understanding of interindividual differences in idiosyncratic DILI. Liver models are also being coupled to other tissue models via microfluidic perfusion to study the intertissue crosstalk upon drug exposure as in a live organism. Here, we review the major advances being made in the engineering of liver models and readouts as they pertain to DILI investigations. We anticipate that engineered human liver models will reduce drug attrition, animal usage, and cases of DILI in humans. Christine Lin and Salman R. Khetani Copyright © 2016 Christine Lin and Salman R. Khetani. All rights reserved. Advances in Molecular Imaging Strategies for In Vivo Tracking of Immune Cells Tue, 20 Sep 2016 14:25:47 +0000 Tracking of immune cells in vivo is a crucial tool for development and optimization of cell-based therapy. Techniques for tracking immune cells have been applied widely for understanding the intrinsic behavior of immune cells and include non-radiation-based techniques such as optical imaging and magnetic resonance imaging (MRI), radiation-based techniques such as computerized tomography (CT), and nuclear imaging including single photon emission computerized tomography (SPECT) and positron emission tomography (PET). Each modality has its own strengths and limitations. To overcome the limitations of each modality, multimodal imaging techniques involving two or more imaging modalities are actively applied. Multimodal techniques allow integration of the strengths of individual modalities. In this review, we discuss the strengths and limitations of currently available preclinical in vivo immune cell tracking techniques and summarize the value of immune cell tracking in the development and optimization of immune cell therapy for various diseases. Ho Won Lee, Prakash Gangadaran, Senthilkumar Kalimuthu, and Byeong-Cheol Ahn Copyright © 2016 Ho Won Lee et al. All rights reserved. Strategies for Lipid Production Improvement in Microalgae as a Biodiesel Feedstock Tue, 20 Sep 2016 13:53:27 +0000 In response to the energy crisis, global warming, and climate changes, microalgae have received a great deal of attention as a biofuel feedstock. Due to a high lipid content in microalgal cells, microalgae present as a promising alternative source for the production of biodiesel. Environmental and culturing condition variations can alter lipid production as well as chemical compositions of microalgae. Therefore, application of the strategies to activate lipid accumulation opens the door for lipid overproduction in microalgae. Until now, many original studies regarding the approaches for enhanced microalgal lipid production have been reported in an effort to push forward the production of microalgal biodiesel. However, the current literature demonstrates fragmented information available regarding the strategies for lipid production improvement. From the systematic point of view, the review highlights the main approaches for microalgal lipid accumulation induction to expedite the application of microalgal biodiesel as an alternative to fossil diesel for sustainable environment. Of the several strategies discussed, the one that is most commonly applied is the design of nutrient (e.g., nitrogen, phosphorus, and sulfur) starvation or limitation. Other viable approaches such as light intensity, temperature, carbon dioxide, salinity stress, and metal influence can also achieve enhanced microalgal lipid production. L. D. Zhu, Z. H. Li, and E. Hiltunen Copyright © 2016 L. D. Zhu et al. All rights reserved. Partially Purified Extracts of Sea Anemone Anemonia viridis Affect the Growth and Viability of Selected Tumour Cell Lines Tue, 20 Sep 2016 09:45:16 +0000 In the last few years, marine species have been investigated for the presence of natural products with anticancer activity. Using reversed phase chromatography, low molecular weight proteins were fractionated from the sea anemone Anemonia viridis. Four different fractions were evaluated for their cytotoxic activity by means of erythrocyte haemolysis test, MTS, and LDH assays. Finally, the antiproliferative activities of three of these fractions were studied on PC3, PLC/PRF/5, and A375 human cancer cell lines. Our analysis revealed that the four fractions showed different protein contents and diverse patterns of activity towards human PBMC and cancer cell lines. Interestingly, fractions III and IV exerted cytotoxic effects on human cells. Conversely, fractions I and II displayed very low toxic effects associated with antiproliferative activities on cancer cell lines. Matteo Bulati, Alessandra Longo, Tiziana Masullo, Sara Vlah, Carmelo Bennici, Angela Bonura, Monica Salamone, Marcello Tagliavia, Aldo Nicosia, Salvatore Mazzola, Paolo Colombo, and Angela Cuttitta Copyright © 2016 Matteo Bulati et al. All rights reserved.