BioMed Research International The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Kölliker’s Organ and the Development of Spontaneous Activity in the Auditory System: Implications for Hearing Dysfunction Wed, 20 Aug 2014 00:00:00 +0000 Prior to the “onset of hearing,” developing cochlear inner hair cells (IHCs) and primary auditory neurons undergo experience-independent activity, which is thought to be important in retaining and refining neural connections in the absence of sound. One of the major hypotheses regarding the origin of such activity involves a group of columnar epithelial supporting cells forming Kölliker’s organ, which is only present during this critical period of auditory development. There is strong evidence for a purinergic signalling mechanism underlying such activity. ATP released through connexin hemichannels may activate P2 purinergic receptors in both Kölliker’s organ and the adjacent IHCs, leading to generation of electrical activity throughout the auditory system. However, recent work has suggested an alternative origin, by demonstrating the ability of IHCs to generate this spontaneous activity without activation by ATP. Regardless, developmental abnormalities of Kölliker’s organ may lead to congenital hearing loss, considering that mutations in ion channels (hemichannels, gap junctions, and calcium channels) involved in Kölliker’s organ activity share strong links with such types of deafness. M. W. Nishani Dayaratne, Srdjan M. Vlajkovic, Janusz Lipski, and Peter R. Thorne Copyright © 2014 M. W. Nishani Dayaratne et al. All rights reserved. Bone Tissue Engineering: Cell Motility, Vascularization, Micro-Nano Scaffolding, and Remodeling Tue, 19 Aug 2014 11:52:23 +0000 Guo-Xian Pei, Yi-Xian Qin, Dietmar Werner Hutmacher, and Zhi-Yong Zhang Copyright © 2014 Guo-Xian Pei et al. All rights reserved. Negative Regulation of GADD34 on Myofibroblasts during Cutaneous Wound Healing Tue, 19 Aug 2014 08:21:28 +0000 The growth arrest and DNA damage-inducible protein, GADD34, has been proved to be involved in TGF-β signaling pathway and correlates with cell death, which are two important mechanisms in regulating myofibroblast differentiation and apoptosis during tissue repair. But roles of GADD34 in myofibroblasts differentiation and apoptosis remain unknown. To investigate the function of GADD34 in these processes, we subjected WT and GADD34−/− mice to dermal wound healing. Here we show that GADD34−/− mice exhibited accelerated wound closure compared with WT mice. In addition, GADD34−/− mice showed increased number of myofibroblasts, elevated collagen production, and decreased cell apoptosis during wound healing. Moreover, we found that GADD34−/− mice showed increased phosphorylation of Smad3 and lower level of cleaved caspase-3. Thus these results indicate that GADD34 appears to suppress myofibroblast differentiation through inhibiting Smad3-dependent TGFβ signal pathway and promote its apoptosis by activating caspase-3 pathway. Lintao Liu, Naomi Nishio, Sachiko Ito, Yuriko Tanaka, and Ken-ichi Isobe Copyright © 2014 Lintao Liu et al. All rights reserved. Cortical Electrophysiological Markers of Language Abilities in Children with Hearing Aids: A Pilot Study Tue, 19 Aug 2014 08:11:40 +0000 Objective. To investigate cortical auditory evoked potentials (CAEPs) in pediatric hearing aid (HA) users, with and without language impairment. Design. CAEPs were measured in 11 pediatric HA users (age: 8–12 years) with moderate bilateral sensorineural hearing loss (HL); participants were classified according to language ability. CAEPs were also measured for a control group of 11 age-matched, normal-hearing (NH) children. Results. HL children without language impairment exhibited normal CAEPs. HL children with language impairment exhibited atypical temporal CAEPs, characterized by the absence of N1c; frontocentral responses displayed normal age-related patterns. Conclusion. Results suggest that abnormal temporal brain function may underlie language impairment in pediatric HA users with moderate sensorineural HL. David Bakhos, Hélène Delage, John Galvin, Emmanuel Lescanne, Sylvie Roux, Frédérique Bonnet-Brilhault, and Nicole Bruneau Copyright © 2014 David Bakhos et al. All rights reserved. Conditioned Media from Microvascular Endothelial Cells Cultured in Simulated Microgravity Inhibit Osteoblast Activity Tue, 19 Aug 2014 07:21:27 +0000 Background and Aims. Gravity contributes to the maintenance of bone integrity. Accordingly, weightlessness conditions during space flight accelerate bone loss and experimental models in real and simulated microgravity show decreased osteoblastic and increased osteoclastic activities. It is well known that the endothelium and bone cells cross-talk and this intercellular communication is vital to regulate bone homeostasis. Because microgravity promotes microvascular endothelial dysfunction, we anticipated that the molecular cross-talk between endothelial cells exposed to simulated microgravity and osteoblasts might be altered. Results. We cultured human microvascular endothelial cells in simulated microgravity using the rotating wall vessel device developed by NASA. Endothelial cells in microgravity show growth inhibition and release higher amounts of matrix metalloproteases type 2 and interleukin-6 than controls. Conditioned media collected from microvascular endothelial cells in simulated microgravity were used to culture human osteoblasts and were shown to retard osteoblast proliferation and inhibit their activity. Discussion. Microvascular endothelial cells in microgravity are growth retarded and release high amounts of matrix metalloproteases type 2 and interleukin-6, which might play a role in retarding the growth of osteoblasts and impairing their osteogenic activity. Conclusions. We demonstrate that since simulated microgravity modulates microvascular endothelial cell function, it indirectly impairs osteoblastic function. Alessandra Cazzaniga, Sara Castiglioni, and Jeanette A. M. Maier Copyright © 2014 Alessandra Cazzaniga et al. All rights reserved. 18F-Fluorodeoxyglucose Positron Emission Tomography/CT Scanning in Diagnosing Vascular Prosthetic Graft Infection Tue, 19 Aug 2014 07:06:59 +0000 Vascular prosthetic graft infection (VPGI) is a severe complication after vascular surgery. CT-scan is considered the diagnostic tool of choice in advanced VPGI. The incidence of a false-negative result using CT is relatively high, especially in the presence of low-grade infections. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scanning has been suggested as an alternative for the diagnosis and assessment of infectious processes. Hybrid 18F-FDG PET/CT has established the role of 18F-FDG PET for the assessment of suspected VPGI, providing accurate anatomic localization of the site of infection. However, there are no clear guidelines for the interpretation of the uptake patterns of 18F-FDG as clinical tool for VPGI. Based on the available literature it is suggested that a linear, diffuse, and homogeneous uptake should not be regarded as an infection whereas focal or heterogeneous uptake with a projection over the vessel on CT is highly suggestive of infection. Nevertheless, 18F-FDG PET and 18F-FDG PET/CT can play an important role in the detection of VPGI and monitoring response to treatment. However an accurate uptake and pattern recognition is warranted and cut-off uptake values and patterns need to be standardized before considering the technique to be the new standard. Ben R. Saleem, Robert A. Pol, Riemer H. J. A. Slart, Michel M. P. J. Reijnen, and Clark J. Zeebregts Copyright © 2014 Ben R. Saleem et al. All rights reserved. Modulation of Steroidogenic Pathway in Rat Granulosa Cells with Subclinical Cd Exposure and Insulin Resistance: An Impact on Female Fertility Tue, 19 Aug 2014 06:35:37 +0000 Changes in lifestyle lead to insulin resistance (IR) in females ultimately predisposing them towards infertility. In addition, cadmium (Cd), an environmental endocrine disruptor, is reported for detrimental effects on granulosa cells, thus leading to ovarian dysfunction. A combination of these factors, lifestyle and environment, seems to play a role in etiology of idiopathic infertility that accounts for 50% amongst the total infertility cases. To address this issue, we made an attempt to investigate the extent of Cd impact on insulin-resistant (IR) granulosa cells. We exposed adult female Charles Foster rats to dexamethasone and confirmed IR condition by fasting insulin resistance index (FIRI). On treatment of IR rats with Cd, the preliminary studies demonstrated prolonged estrous cyclicity, decrease in serum estradiol concentrations, abnormal histology of ovary, and increased granulosa cell death. Further gene and protein expression studies of steroidogenic acute regulatory (StAR) protein, 17β-hydroxysteroid dehydrogenase (17β-HSD), and cytochrome P450 aromatase (CYP19A1) were performed. Protein expression studies demonstrated significant decrease in treated groups when compared with control. Study revealed that, in spite of the molecular parameters being affected at varied level, overall ovarian physiology is maximally affected in IR and Cd coexposed group, thus mimicking the condition similar to those prevailing in infertile females. Muskaan Belani, Nupur Purohit, Prakash Pillai, Sharad Gupta, and Sarita Gupta Copyright © 2014 Muskaan Belani et al. All rights reserved. Evaluation of Dried Sweet Sorghum Stalks as Raw Material for Methane Production Tue, 19 Aug 2014 06:07:02 +0000 The potential of utilizing dried sweet sorghum stalks as raw material for anaerobic digestion has been evaluated. Two different treatments were tested, a mild thermal and an enzymatic, alone or in combination. Thermal pretreatment was found to decrease the methane yields, whereas one-step enzymatic treatment resulted in a significant increase of 15.1% comparing to the untreated sweet sorghum. Subsequently, in order to increase the total methane production, the combined effect of enzyme load and I/S on methane yields from sweet sorghum was evaluated by employing response surface methodology. The obtained model showed that the maximum methane yield that could be achieved is 296 mL CH4/g VS at I/S ratio of 0.35 with the addition of 11.12 FPU/g sweet sorghum. Leonidas Matsakas, Ulrika Rova, and Paul Christakopoulos Copyright © 2014 Leonidas Matsakas et al. All rights reserved. Microsoft Kinect-Based Artificial Perception System for Control of Functional Electrical Stimulation Assisted Grasping Tue, 19 Aug 2014 05:17:02 +0000 We present a computer vision algorithm that incorporates a heuristic model which mimics a biological control system for the estimation of control signals used in functional electrical stimulation (FES) assisted grasping. The developed processing software acquires the data from Microsoft Kinect camera and implements real-time hand tracking and object analysis. This information can be used to identify temporal synchrony and spatial synergies modalities for FES control. Therefore, the algorithm acts as artificial perception which mimics human visual perception by identifying the position and shape of the object with respect to the position of the hand in real time during the planning phase of the grasp. This artificial perception used within the heuristically developed model allows selection of the appropriate grasp and prehension. The experiments demonstrate that correct grasp modality was selected in more than 90% of tested scenarios/objects. The system is portable, and the components are low in cost and robust; hence, it can be used for the FES in clinical or even home environment. The main application of the system is envisioned for functional electrical therapy, that is, intensive exercise assisted with FES. Matija Štrbac, Slobodan Kočović, Marko Marković, and Dejan B. Popović Copyright © 2014 Matija Štrbac et al. All rights reserved. Spaceflight Affects Postnatal Development of the Aortic Wall in Rats Tue, 19 Aug 2014 00:00:00 +0000 We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam). The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta. Shin-ichiro Katsuda, Masao Yamasaki, Hidefumi Waki, Masao Miyake, Hirotaka O-ishi, Kiyoaki Katahira, Tadanori Nagayama, Yukako Miyamoto, Masamitsu Hasegawa, Haruyuki Wago, Toshiyasu Okouchi, and Tsuyoshi Shimizu Copyright © 2014 Shin-ichiro Katsuda et al. All rights reserved. Defensins and Sepsis Tue, 19 Aug 2014 00:00:00 +0000 Sepsis is a leading cause of mortality and morbidity in the critical illness. Multiple immune inflammatory processes take part in the pathogenesis of sepsis. Defensins are endogenous antimicrobial peptides with three disulphide bonds created by six cysteine residues. Besides the intrinsic microbicidal properties, defensins are active players which modulate both innate and adaptive immunity against various infections. Defensins can recruit neutrophils, enhance phagocytosis, chemoattract T cells and dendritic cells, promote complement activation, and induce IL-1β production and pyrotosis. Previous publications have documented that defensins play important roles in a series of immune inflammatory diseases including sepsis. This review aims to briefly summarize in vitro, in vivo, and genetic studies on defensins’ effects as well as corresponding mechanisms within sepsis and highlights their promising findings which may be potential targets in future therapies of sepsis. Guo-Hao Xie, Qi-Xing Chen, Bao-Li Cheng, and Xiang-Ming Fang Copyright © 2014 Guo-Hao Xie et al. All rights reserved. Inhibition of Hydrogen Sulfide Production by Gene Silencing Attenuates Inflammatory Activity by Downregulation of NF-κB and MAP Kinase Activity in LPS-Activated RAW 264.7 Cells Tue, 19 Aug 2014 00:00:00 +0000 Hydrogen sulfide is an endogenous inflammatory mediator produced by the activity of cystathionine γ-lyase (CSE) in macrophages. The objective of this study was to explore the mechanism by which hydrogen sulfide acts as an inflammatory mediator in lipopolysaccharide- (LPS-) induced macrophages. In this study, we used small interfering RNA (siRNA) to inhibit CSE expression in macrophages. We found that CSE silencing siRNA could reduce the LPS-induced activation of transcription factor nuclear factor-κB (NF-κB) significantly. Phosphorylation and activation of extra cellular signal-regulated kinase 1/2 (ERK1/2) increased in LPS-induced macrophages. We showed that phosphorylation of ERK in LPS-induced RAW 264.7 cells reached a peak 30 min after activation. Our findings show that silencing CSE gene by siRNA reduces phosphorylation and activation of ERK1/2 in LPS-induced RAW 264.7 cells. These findings suggest that siRNA reduces the inflammatory effects of hydrogen sulfide through the ERK-NF-κB signalling pathway and hydrogen sulfide plays its inflammatory role through ERK-NF-κB pathway in these cells. Alireza Badiei, Nethaji Muniraj, Stephen Chambers, and Madhav Bhatia Copyright © 2014 Alireza Badiei et al. All rights reserved. Adjuvant Cardioprotection in Cardiac Surgery: Update Tue, 19 Aug 2014 00:00:00 +0000 Cardiac surgery patients are now more risky in terms of age, comorbidities, and the need for complex procedures. It brings about reperfusion injury, which leads to dysfunction and/or loss of part of the myocardium. These groups of patients have a higher incidence of postoperative complications and mortality. One way of augmenting intraoperative myocardial protection is the phenomenon of myocardial conditioning, elicited with brief nonlethal episodes of ischaemia-reperfusion. In addition, drugs are being tested that mimic ischaemic conditioning. Such cardioprotective techniques are mainly focused on reperfusion injury, a complex response of the organism to the restoration of coronary blood flow in ischaemic tissue, which can lead to cell death. Extensive research over the last three decades has revealed the basic mechanisms of reperfusion injury and myocardial conditioning, suggesting its therapeutic potential. But despite the enormous efforts that have been expended in preclinical studies, almost all cardioprotective therapies have failed in the third phase of clinical trials. One reason is that evolutionary young cellular mechanisms of protection against oxygen handling are not very robust. Ischaemic conditioning, which is among these, is also limited by this. At present, the prevailing belief is that such options of treatment exist, but their full employment will not occur until subquestions and methodological issues with the transfer into clinical practice have been resolved. Robert Wagner, Pavel Piler, Zufar Gabbasov, Junko Maruyama, Kazuo Maruyama, Jiri Nicovsky, and Peter Kruzliak Copyright © 2014 Robert Wagner et al. All rights reserved. Evaluation of the Performance of Females as Light Infantry Soldiers Mon, 18 Aug 2014 12:59:44 +0000 A few countries permit women to serve in combat roles, but their long term performance in these positions has not been reported. The incidences of overuse injuries and attrition of 85 male and 235 female recruits in a light infantry brigade was followed in a three-year prospective study. Females were shorter (162 cm, CI 161–163 cm) than males (174 cm, CI 173–176), had more body fat (18.9 kg, CI 18.2–19.6 kg) than males (12.6 kg, 11.3–13.8 kg), had lower O2max (36.8 mL·min−1·kg−1, CI 35.8–37.78 mL·min−1·kg−1) than males (50.48 mL·min−1·kg−1, CI 48.4 to 52.48 mL·min−1·kg−1), had more stress fractures (21.0%, 95% CI 16.2–26.5%) than males (2.3%, CI 0.3–8.2%), and had more anterior knee pain (41.2%, CI 34.9–47.7%) than males (24.7%, CI 16.0–35.2%). Three-year attrition was 28% CI 22–34% for females and 37% CI 26–48% for males. The females in this study successfully served as light infantry soldiers. Their lower fitness and high incidence of overuse injuries might impede service as regular infantry soldiers. Aharon S. Finestone, Charles Milgrom, Ran Yanovich, Rachel Evans, Naama Constantini, and Daniel S. Moran Copyright © 2014 Aharon S. Finestone et al. All rights reserved. The Presence of Biomarker Enzymes of Selected Scleractinian Corals of Palk Bay, Southeast Coast of India Mon, 18 Aug 2014 12:06:57 +0000 The health and existence of coral reefs are in danger by an increasing range of environmental and anthropogenic impacts. The causes of coral reef decline include worldwide climate change, shoreline development, habitat destruction, pollution, sedimentation and overexploitation. These disasters have contributed to an estimated loss of 27% of the reefs. If the current pressure continues unabated, the estimated loss of coral reef will be about 60% by the year 2030. Therefore, the present study was aimed to analyze the enzymes involved in stress induced by coral pathogen and its resistance. We focused on the enzymes involved in melanin synthesis pathway (phenoloxidase (PO) and peroxidases (POD)) and free radical scavenging enzymes (super oxide dismutase (SOD), catalase (CAT)) and glutathione peroxidase (Gpx) in selected scleractinian corals such as Acropora formosa, Echinopora lamellosa, Favia favus, Favites halicora, Porites sp., and Anacropora forbesi. Overall, PO activity of coral was significantly lower than that of zooxanthellae except for Favia favus. Coral colonies with lower PO and POD activities are prone to disease. Maximum antioxidant defensive enzymes were observed in Favia favus followed by Echinopora lamellose. It is concluded that assay of these enzymes can be used as biomarkers for identifying the susceptibility of corals towards coral bleaching induced by pathogen. R. Anithajothi, K. Duraikannu, G. Umagowsalya, and C. M. Ramakritinan Copyright © 2014 R. Anithajothi et al. All rights reserved. Advances in Prostate Cancer Research and Treatment Mon, 18 Aug 2014 11:21:22 +0000 Lorenzo Livi, Andrea M. Isidori, David Sherris, and Giovanni Luca Gravina Copyright © 2014 Lorenzo Livi et al. All rights reserved. Nonthermal Pasteurization of Fermented Green Table Olives by means of High Hydrostatic Pressure Processing Mon, 18 Aug 2014 11:18:10 +0000 Green fermented olives cv. Halkidiki were subjected to different treatments of high hydrostatic pressure (HHP) processing (400, 450, and 500 MPa for 15 or 30 min). Total viable counts, lactic acid bacteria and yeasts/moulds, and the physicochemical characteristics of the product (pH, colour, and firmness) were monitored right after the treatment and after 7 days of storage at 20°C to allow for recovery of injured cells. The treatments at 400 MPa for 15 and 30 min, 450 MPa for 15 and 30 min, and 500 MPa for 15 min were found insufficient as a recovery of the microbiota was observed. The treatment at 500 MPa for 30 min was effective in reducing the olive microbiota below the detection limit of the enumeration method after the treatment and after 1 week of storage and was chosen as being more appropriate for storing olives for an extended time period (5 months). After 5 months of storage at 20°C, no microbiota was detected in treated samples, while significant changes for both HHP treated and untreated olives were observed for colour parameters only (minor degradation). In conclusion, HHP treatment may introduce a reliable nonthermal pasteurization method to extend the microbiological shelf-life of fermented table olives. Anthoula A. Argyri, Efstathios Z. Panagou, George-John E. Nychas, and Chrysoula C. Tassou Copyright © 2014 Anthoula A. Argyri et al. All rights reserved. Rhubarb Tannins Extract Inhibits the Expression of Aquaporins 2 and 3 in Magnesium Sulphate-Induced Diarrhoea Model Mon, 18 Aug 2014 11:10:52 +0000 Tannins, a group of major active components of Chinese rhubarb and widely distributed in nature, have a significant antidiarrhoeal activity. Aquaporins (AQPs) 2 and 3 play important roles in regulating water transfer during diarrhoea. The present study aims to determine the effect of the total tannins extract of rhubarb on aquaporins (AQPs) 2 and 3 in diarrhoea mice and HT-29 cells both induced by magnesium sulphate (MgSO4). Our results showed that rhubarb tannins extract (RTE) significantly decreased the faecal water content in colon and evaluation index of defecation of diarrhoea mice. Interestingly, RTE could markedly reduce the mRNA and protein expression levels of AQPs 2 and 3 in apical and lateral mucosal epithelial cells in the colons of diarrhoea mice and HT-29 cells both induced by MgSO4 in a dose-dependent manner. Furthermore, RTE suppressed the production of cyclic monophosphate- (cAMP-) dependent protein kinase A catalytic subunits α (PKA C-α) and phosphorylated cAMP response element-binding protein (p-CREB, Ser133) in MgSO4-induced HT-29 cells. Our data showed for the first time that RTE inhibit AQPs 2 and 3 expression in vivo and in vitro via downregulating PKA/p-CREB signal pathway, which accounts for the antidiarrhoeal effect of RTE. Chunfang Liu, Yanfang Zheng, Wen Xu, Hui Wang, and Na Lin Copyright © 2014 Chunfang Liu et al. All rights reserved. Large-Scale Protein-Protein Interactions Detection by Integrating Big Biosensing Data with Computational Model Mon, 18 Aug 2014 10:52:22 +0000 Protein-protein interactions are the basis of biological functions, and studying these interactions on a molecular level is of crucial importance for understanding the functionality of a living cell. During the past decade, biosensors have emerged as an important tool for the high-throughput identification of proteins and their interactions. However, the high-throughput experimental methods for identifying PPIs are both time-consuming and expensive. On the other hand, high-throughput PPI data are often associated with high false-positive and high false-negative rates. Targeting at these problems, we propose a method for PPI detection by integrating biosensor-based PPI data with a novel computational model. This method was developed based on the algorithm of extreme learning machine combined with a novel representation of protein sequence descriptor. When performed on the large-scale human protein interaction dataset, the proposed method achieved 84.8% prediction accuracy with 84.08% sensitivity at the specificity of 85.53%. We conducted more extensive experiments to compare the proposed method with the state-of-the-art techniques, support vector machine. The achieved results demonstrate that our approach is very promising for detecting new PPIs, and it can be a helpful supplement for biosensor-based PPI data detection. Zhu-Hong You, Shuai Li, Xin Gao, Xin Luo, and Zhen Ji Copyright © 2014 Zhu-Hong You et al. All rights reserved. A Review on Plants Used for Improvement of Sexual Performance and Virility Mon, 18 Aug 2014 09:59:03 +0000 The use of plant or plant-based products to stimulate sexual desire and to enhance performance and enjoyment is almost as old as the human race itself. The present paper reviews the active, natural principles, and crude extracts of plants, which have been useful in sexual disorders, have potential for improving sexual behaviour and performance, and are helpful in spermatogenesis and reproduction. Review of refereed journals and scientific literature available in electronic databases and traditional literature available in India was extensively performed. The work reviews correlation of the evidence with traditional claims, elucidation, and evaluation of a plausible concept governing the usage of plants as aphrodisiac in total. Phytoconstituents with known structures have been classified in appropriate chemical groups and the active crude extracts have been tabulated. Data on their pharmacological activity, mechanism of action, and toxicity are reported. The present review provides an overview of the herbs and their active molecule with claims for improvement of sexual behaviour. A number of herbal drugs have been validated for their effect on sexual behavior and fertility and can therefore serve as basis for the identification of new chemical leads useful in sexual and erectile dysfunction. Nagendra Singh Chauhan, Vikas Sharma, V. K. Dixit, and Mayank Thakur Copyright © 2014 Nagendra Singh Chauhan et al. All rights reserved. Involvement of p53 Mutation and Mismatch Repair Proteins Dysregulation in NNK-Induced Malignant Transformation of Human Bronchial Epithelial Cells Mon, 18 Aug 2014 09:14:35 +0000 Genome integrity is essential for normal cellular functions and cell survival. Its instability can cause genetic aberrations and is considered as a hallmark of most cancers. To investigate the carcinogenesis process induced by tobacco-specific carcinogen NNK, we studied the dynamic changes of two important protectors of genome integrity, p53 and MMR system, in malignant transformation of human bronchial epithelial cells after NNK exposure. Our results showed that the expression of MLH1, one of the important MMR proteins, was decreased early and maintained the downregulation during the transformation in a histone modification involved and DNA methylation-independent manner. Another MMR protein PMS2 also displayed a declined expression while being in a later stage of transformation. Moreover, we conducted p53 mutation analysis and revealed a mutation at codon 273 which led to the replacement of arginine by histidine. With the mutation, DNA damage-induced activation of p53 was significantly impaired. We further reintroduced the wild-type p53 into the transformed cells, and the malignant proliferation can be abrogated by inducing cell cycle arrest and apoptosis. These findings indicate that p53 and MMR system play an important role in the initiation and progression of NNK-induced transformation, and p53 could be a potential therapeutic target for tobacco-related cancers. Ying Shen, Shuilian Zhang, Xiaobin Huang, Kailin Chen, Jing Shen, and Zhengyang Wang Copyright © 2014 Ying Shen et al. All rights reserved. Hepatosplenic Sarcoidosis: Contrast-Enhanced Ultrasound Findings and Implications for Clinical Practice Mon, 18 Aug 2014 09:13:36 +0000 Sarcoidosis is a complex granulomatous disease that affects virtually every organ and tissue, with a prevalence that varies significantly among the sites involved. The role of conventional imaging, such as computed tomography and magnetic resonance imaging, in the assessment of hepatosplenic sarcoidosis is well established by revealing organ enlargement, multiple discrete nodules, and lymphadenopathy. In this review, we aim to describe contrast-enhanced ultrasound (CEUS) findings in liver and spleen involvement by sarcoidosis, reporting evidence from the literature and cases from our experience, after a brief update on safety profile, cost-effectiveness, and clinical indications of this novel technique. Furthermore, we highlight potential advantages of CEUS in assessing hepatosplenic sarcoidosis that may be useful in the clinical practice. Claudio Tana, Christoph F. Dietrich, and Cosima Schiavone Copyright © 2014 Claudio Tana et al. All rights reserved. An Improved Approach for Accurate and Efficient Measurement of Common Carotid Artery Intima-Media Thickness in Ultrasound Images Mon, 18 Aug 2014 09:01:53 +0000 The intima-media thickness (IMT) of common carotid artery (CCA) can serve as an important indicator for the assessment of cardiovascular diseases (CVDs). In this paper an improved approach for automatic IMT measurement with low complexity and high accuracy is presented. 100 ultrasound images from 100 patients were tested with the proposed approach. The ground truth (GT) of the IMT was manually measured for six times and averaged, while the automatic segmented (AS) IMT was computed by the algorithm proposed in this paper. The mean difference ± standard deviation between AS and GT IMT is 0.0231 ± 0.0348 mm, and the correlation coefficient between them is 0.9629. The computational time is 0.3223 s per image with MATLAB under Windows XP on an Intel Core 2 Duo CPU E7500 @2.93 GHz. The proposed algorithm has the potential to achieve real-time measurement under Visual Studio. Qiang Li, Wei Zhang, Xin Guan, Yu Bai, and Jing Jia Copyright © 2014 Qiang Li et al. All rights reserved. Phenotypic Switch Induced by Simulated Microgravity on MDA-MB-231 Breast Cancer Cells Mon, 18 Aug 2014 08:24:31 +0000 Microgravity exerts dramatic effects on cell morphology and functions, by disrupting cytoskeleton and adhesion structures, as well as by interfering with biochemical pathways and gene expression. Impairment of cells behavior has both practical and theoretical significance, given that investigations of mechanisms involved in microgravity-mediated effects may shed light on how biophysical constraints cooperate in shaping complex living systems. By exposing breast cancer MDA-MB-231 cells to simulated microgravity (~0.001 g), we observed the emergence of two morphological phenotypes, characterized by distinct membrane fractal values, surface area, and roundness. Moreover, the two phenotypes display different aggregation profiles and adherent behavior on the substrate. These morphological differences are mirrored by the concomitant dramatic functional changes in cell processes (proliferation and apoptosis) and signaling pathways (ERK, AKT, and Survivin). Furthermore, cytoskeleton undergoes a dramatic reorganization, eventually leading to a very different configuration between the two populations. These findings could be considered adaptive and reversible features, given that, by culturing microgravity-exposed cells into a normal gravity field, cells are enabled to recover their original phenotype. Overall these data outline the fundamental role gravity plays in shaping form and function in living systems. Maria Grazia Masiello, Alessandra Cucina, Sara Proietti, Alessandro Palombo, Pierpaolo Coluccia, Fabrizio D’Anselmi, Simona Dinicola, Alessia Pasqualato, Veronica Morini, and Mariano Bizzarri Copyright © 2014 Maria Grazia Masiello et al. All rights reserved. Phylogenetic Information Content of Copepoda Ribosomal DNA Repeat Units: ITS1 and ITS2 Impact Mon, 18 Aug 2014 08:19:35 +0000 The utility of various regions of the ribosomal repeat unit for phylogenetic analysis was examined in 16 species representing four families, nine genera, and two orders of the subclass Copepoda (Crustacea). Fragments approximately 2000 bp in length containing the ribosomal DNA (rDNA) 18S and 28S gene fragments, the 5.8S gene, and the internal transcribed spacer regions I and II (ITS1 and ITS2) were amplified and analyzed. The DAMBE (Data Analysis in Molecular Biology and Evolution) software was used to analyze the saturation of nucleotide substitutions; this test revealed the suitability of both the 28S gene fragment and the ITS1/ITS2 rDNA regions for the reconstruction of phylogenetic trees. Distance (minimum evolution) and probabilistic (maximum likelihood, Bayesian) analyses of the data revealed that the 28S rDNA and the ITS1 and ITS2 regions are informative markers for inferring phylogenetic relationships among families of copepods and within the Cyclopidae family and associated genera. Split-graph analysis of concatenated ITS1/ITS2 rDNA regions of cyclopoid copepods suggested that the Mesocyclops, Thermocyclops, and Macrocyclops genera share complex evolutionary relationships. This study revealed that the ITS1 and ITS2 regions potentially represent different phylogenetic signals. Maxim V. Zagoskin, Valentina I. Lazareva, Andrey K. Grishanin, and Dmitry V. Mukha Copyright © 2014 Maxim V. Zagoskin et al. All rights reserved. Mechanotransduction in Musculoskeletal Tissue Regeneration: Effects of Fluid Flow, Loading, and Cellular-Molecular Pathways Mon, 18 Aug 2014 07:50:39 +0000 While mechanotransductive signal is proven essential for tissue regeneration, it is critical to determine specific cellular responses to such mechanical signals and the underlying mechanism. Dynamic fluid flow induced by mechanical loading has been shown to have the potential to regulate bone adaptation and mitigate bone loss. Mechanotransduction pathways are of great interests in elucidating how mechanical signals produce such observed effects, including reduced bone loss, increased bone formation, and osteogenic cell differentiation. The objective of this review is to develop a molecular understanding of the mechanotransduction processes in tissue regeneration, which may provide new insights into bone physiology. We discussed the potential for mechanical loading to induce dynamic bone fluid flow, regulation of bone adaptation, and optimization of stimulation parameters in various loading regimens. The potential for mechanical loading to regulate microcirculation is also discussed. Particularly, attention is allotted to the potential cellular and molecular pathways in response to loading, including osteocytes associated with Wnt signaling, elevation of marrow stem cells, and suppression of adipotic cells, as well as the roles of LRP5 and microRNA. These data and discussions highlight the complex yet highly coordinated process of mechanotransduction in bone tissue regeneration. Yi-Xian Qin and Minyi Hu Copyright © 2014 Yi-Xian Qin and Minyi Hu. All rights reserved. Retrospective Comparative Study of the Effects of Dendritic Cell Vaccine and Cytokine-Induced Killer Cell Immunotherapy with that of Chemotherapy Alone and in Combination for Colorectal Cancer Mon, 18 Aug 2014 07:41:02 +0000 Purpose. This retrospective study determined the delayed-type hypersensitivity (DTH) skin test and safety of dendritic cell (DC) vaccine and cytokine-induced killer (CIK) cell immunotherapy and the survival compared to chemotherapy in 239 colorectal cancer (CRC) patients. Methods. DTH and safety of the immunotherapy were recorded. The overall survival (OS) and disease free survival curves were compared according to the immunotherapy and/or chemotherapy received with Kaplan-Meier estimates. Results. Of the 70 patients who received immunotherapy, 62.86% had a positive DTH skin test, 38.57% developed fever, 47.14% developed insomnia, 38.57% developed anorexia, 4.29% developed joint soreness, and 11.43% developed skin rash. For 204 resectable CRC patients, median survival time (MST) (198.00 days) was significantly longer in patients with immunotherapy plus chemotherapy than with chemotherapy alone (106.00 days) . For 35 patients with unresectable or postsurgery relapsed CRC and who were confirmed to be dead, no statistical difference was observed in the MST between the patients treated with immunotherapy and with chemotherapy . MST in the patients treated with chemotherapy plus immunotherapy was 154 days longer than that of patients treated with chemotherapy alone . Conclusions. DC vaccination and CIK immunotherapy did not cause severe adverse effects, induce immune response against CRC, and prolong OS. Jingxiu Niu, Yanjie Ren, Tianyu Zhang, Xuejing Yang, Wei Zhu, Hui Zhu, Jing Li, Jiali Li, and Yan Pang Copyright © 2014 Jingxiu Niu et al. All rights reserved. Evolution of Autologous Chondrocyte Repair and Comparison to Other Cartilage Repair Techniques Mon, 18 Aug 2014 07:03:32 +0000 Articular cartilage defects have been addressed using microfracture, abrasion chondroplasty, or osteochondral grafting, but these strategies do not generate tissue that adequately recapitulates native cartilage. During the past 25 years, promising new strategies using assorted scaffolds and cell sources to induce chondrocyte expansion have emerged. We reviewed the evolution of autologous chondrocyte implantation and compared it to other cartilage repair techniques. Methods. We searched PubMed from 1949 to 2014 for the keywords “autologous chondrocyte implantation” (ACI) and “cartilage repair” in clinical trials, meta-analyses, and review articles. We analyzed these articles, their bibliographies, our experience, and cartilage regeneration textbooks. Results. Microfracture, abrasion chondroplasty, osteochondral grafting, ACI, and autologous matrix-induced chondrogenesis are distinguishable by cell source (including chondrocytes and stem cells) and associated scaffolds (natural or synthetic, hydrogels or membranes). ACI seems to be as good as, if not better than, microfracture for repairing large chondral defects in a young patient’s knee as evaluated by multiple clinical indices and the quality of regenerated tissue. Conclusion. Although there is not enough evidence to determine the best repair technique, ACI is the most established cell-based treatment for full-thickness chondral defects in young patients. Ashvin K. Dewan, Matthew A. Gibson, Jennifer H. Elisseeff, and Michael E. Trice Copyright © 2014 Ashvin K. Dewan et al. All rights reserved. Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer Mon, 18 Aug 2014 07:02:32 +0000 Drug repositioning is a popular approach in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development time. Non-small-cell lung cancer (NSCLC) is one of the leading causes of death worldwide. To reduce the biological heterogeneity effects among different individuals, both normal and cancer tissues were taken from the same patient, hence allowing pairwise testing. By comparing early- and late-stage cancer patients, we can identify stage-specific NSCLC genes. Differentially expressed genes are clustered separately to form up- and downregulated communities that are used as queries to perform enrichment analysis. The results suggest that pathways for early- and late-stage cancers are different. Sets of up- and downregulated genes were submitted to the cMap web resource to identify potential drugs. To achieve high confidence drug prediction, multiple microarray experimental results were merged by performing meta-analysis. The results of a few drug findings are supported by MTT assay or clonogenic assay data. In conclusion, we have been able to assess the potential existing drugs to identify novel anticancer drugs, which may be helpful in drug repositioning discovery for NSCLC. Chien-Hung Huang, Peter Mu-Hsin Chang, Yong-Jie Lin, Cheng-Hsu Wang, Chi-Ying F. Huang, and Ka-Lok Ng Copyright © 2014 Chien-Hung Huang et al. All rights reserved. Evaluation of the Effect of Andrographolide on Atherosclerotic Rabbits Induced by Porphyromonas gingivalis Mon, 18 Aug 2014 07:00:58 +0000 Epidemiologic evidence has demonstrated significant associations between atherosclerosis and Porphyromonas gingivalis (Pg). We had investigated the effect of andrographolide (AND) on atherosclerosis induced by Pg in rabbits. For experimental purpose, we separated thirty male white New Zealand rabbits into 5 groups. Group 1 received standard food pellets; Groups 2–5 were orally challenged with Pg; Group 3 received atorvastatin (AV, 5 mg/kg), and Groups 4-5 received 10 and 20 mg/kg of AND, respectively, over 12 weeks. Groups treated with AND showed significant decrease in TC, TG, and LDL levels () and significant increase in HDL level in the serum of rabbits. Furthermore, the treated groups (G3–G5) exhibited reductions in interleukins (IL-1β and IL-6) and C-reactive protein (CRP) as compared to atherogenicgroup (G2). The histological results showed that the thickening of atherosclerotic plaques were less significant in treated groups (G3–G5) compared with atherogenicgroup (G2). Also, alpha-smooth muscle actin (α-SMA) staining decreased within the plaques of atherogenicgroup (G2), while it was increased in treated groups (G3–G5). Lastly, groups treated with AV and AND (G3–G5) showed significant reduction of CD36 expression () compared to atherogenicgroup (G2). These results substantially proved that AND contain antiatherogenic activity. Rami Al Batran, Fouad Al-Bayaty, Mazen M. Jamil Al-Obaidi, Saba F. Hussain, and Tengku Z. Mulok Copyright © 2014 Rami Al Batran et al. All rights reserved.