Oxidative Medicine and Cellular Longevity http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Reactive Oxygen Species in Stem Cells Tue, 28 Jul 2015 06:22:56 +0000 http://www.hindawi.com/journals/omcl/2015/159080/ Tullia Maraldi, Cristina Angeloni, Elisa Giannoni, and Christian Sell Copyright © 2015 Tullia Maraldi et al. All rights reserved. Upregulation of Multidrug Resistance-Associated Protein 1 by Allyl Isothiocyanate in Human Bronchial Epithelial Cell: Involvement of c-Jun N-Terminal Kinase Signaling Pathway Mon, 27 Jul 2015 12:12:44 +0000 http://www.hindawi.com/journals/omcl/2015/903782/ Multidrug resistance-associated protein 1 (MRP1) plays a protective role in the etiology and progression of chronic obstructive pulmonary disease (COPD) which results from oxidative stress and inflammation of lung injury. The lower functional MRP1 activity is related to COPD development. Our previous study showed that Allyl isothiocyanate (AITC) induced the expression and activity of MRP1 in a dose-dependent manner. However, which signaling pathway contributes to the upregulation of MRP1 by AITC is unclear. In this study, signaling pathway specific inhibitors were used to examine the mechanism of AITC. We found that JNK inhibitor SP600125 treatment decreased MRP1 mRNA expression in 16HBE14o- cells. But the ERK inhibitor U0126 or PI3K/Akt inhibitor LY294002 produced no obvious effect. The AITC-induced increase of MRP1 mRNA expression was abolished by cotreatment of SP600125, while it was not obviously affected by U0126 or LY294002. Furthermore, AITC acivates the JNK signaling pathway in 16HBE14o- cells. Finally, we found that JNK pathway mediated the upregulation of AITC-induced expression and function of MRP1. Taken together, our results indicated that AITC increased the expression and the activity of MRP1 via a JNK-dependent pathway. ERK and PI3K signaling pathway were not involved in the expression of MRP1 mRNA. Shujun Wang, Shanshan Wang, Chenyin Wang, Yajun Chen, Jie Li, Xueqi Wang, Dianlei Wang, Zegeng Li, Zhaoliang Peng, and Ling Fan Copyright © 2015 Shujun Wang et al. All rights reserved. Reactive Oxygen Species Are Required for Human Mesenchymal Stem Cells to Initiate Proliferation after the Quiescence Exit Mon, 27 Jul 2015 08:06:14 +0000 http://www.hindawi.com/journals/omcl/2015/502105/ The present study focuses on the involvement of reactive oxygen species (ROS) in the process of mesenchymal stem cells “waking up” and entering the cell cycle after the quiescence. Using human endometrial mesenchymal stem cells (eMSCs), we showed that intracellular basal ROS level is positively correlated with the proliferative status of the cell cultures. Our experiments with the eMSCs synchronized in the G0 phase of the cell cycle revealed a transient increase in the ROS level upon the quiescence exit after stimulation of the cell proliferation. This increase was registered before the eMSC entry to the S-phase of the cell cycle, and elimination of this increase by antioxidants (N-acetyl-L-cysteine, Tempol, and Resveratrol) blocked G1–S-phase transition. Similarly, a cell cycle arrest which resulted from the antioxidant treatment was observed in the experiments with synchronized human mesenchymal stem cells derived from the adipose tissue. Thus, we showed that physiologically relevant level of ROS is required for the initiation of human mesenchymal stem cell proliferation and that low levels of ROS due to the antioxidant treatment can block the stem cell self-renewal. O. G. Lyublinskaya, Ya. G. Borisov, N. A. Pugovkina, I. S. Smirnova, Ju. V. Obidina, Ju. S. Ivanova, V. V. Zenin, A. N. Shatrova, A. V. Borodkina, N. D. Aksenov, V. I. Zemelko, E. B. Burova, M. V. Puzanov, and N. N. Nikolsky Copyright © 2015 O. G. Lyublinskaya et al. All rights reserved. Controlling Redox Status for Stem Cell Survival, Expansion, and Differentiation Mon, 27 Jul 2015 08:03:24 +0000 http://www.hindawi.com/journals/omcl/2015/105135/ Reactive oxygen species (ROS) have long been considered as pathological agents inducing apoptosis under adverse culture conditions. However, recent findings have challenged this dogma and physiological levels of ROS are now considered as secondary messengers, mediating numerous cellular functions in stem cells. Stem cells represent important tools for tissue engineering, drug screening, and disease modeling. However, the safe use of stem cells for clinical applications still requires culture improvements to obtain functional cells. With the examples of mesenchymal stem cells (MSCs) and pluripotent stem cells (PSCs), this review investigates the roles of ROS in the maintenance of self-renewal, proliferation, and differentiation of stem cells. In addition, this work highlights that the tight control of stem cell microenvironment, including cell organization, and metabolic and mechanical environments, may be an effective approach to regulate endogenous ROS generation. Taken together, this paper indicates the need for better quantification of ROS towards the accurate control of stem cell fate. Sébastien Sart, Liqing Song, and Yan Li Copyright © 2015 Sébastien Sart et al. All rights reserved. Redox Regulation in Cancer Stem Cells Sun, 26 Jul 2015 11:57:08 +0000 http://www.hindawi.com/journals/omcl/2015/750798/ Reactive oxygen species (ROS) and ROS-dependent (redox regulation) signaling pathways and transcriptional activities are thought to be critical in stem cell self-renewal and differentiation during growth and organogenesis. Aberrant ROS burst and dysregulation of those ROS-dependent cellular processes are strongly associated with human diseases including many cancers. ROS levels are elevated in cancer cells partially due to their higher metabolism rate. In the past 15 years, the concept of cancer stem cells (CSCs) has been gaining ground as the subpopulation of cancer cells with stem cell-like properties and characteristics have been identified in various cancers. CSCs possess low levels of ROS and are responsible for cancer recurrence after chemotherapy or radiotherapy. Unfortunately, how CSCs control ROS production and scavenging and how ROS-dependent signaling pathways contribute to CSCs function remain poorly understood. This review focuses on the role of redox balance, especially in ROS-dependent cellular processes in cancer stem cells (CSCs). We updated recent advances in our understanding of ROS generation and elimination in CSCs and their effects on CSC self-renewal and differentiation through modulating signaling pathways and transcriptional activities. The review concludes that targeting CSCs by manipulating ROS metabolism/dependent pathways may be an effective approach for improving cancer treatment. Shijie Ding, Chunbao Li, Ninghui Cheng, Xiaojiang Cui, Xinglian Xu, and Guanghong Zhou Copyright © 2015 Shijie Ding et al. All rights reserved. Nuclear Nox4 Role in Stemness Power of Human Amniotic Fluid Stem Cells Sun, 26 Jul 2015 08:34:07 +0000 http://www.hindawi.com/journals/omcl/2015/101304/ Human amniotic fluid stem cells (AFSC) are an attractive source for cell therapy due to their multilineage differentiation potential and accessibility advantages. However the clinical application of human stem cells largely depends on their capacity to expand in vitro, since there is an extensive donor-to-donor heterogeneity. Reactive oxygen species (ROS) and cellular oxidative stress are involved in many physiological and pathophysiological processes of stem cells, including pluripotency, proliferation, differentiation, and stress resistance. The mode of action of ROS is also dependent on the localization of their target molecules. Thus, the modifications induced by ROS can be separated depending on the cellular compartments they affect. NAD(P)H oxidase family, particularly Nox4, has been known to produce ROS in the nucleus. In the present study we show that Nox4 nuclear expression (nNox4) depends on the donor and it correlates with the expression of transcription factors involved in stemness regulation, such as Oct4, SSEA-4, and Sox2. Moreover nNox4 is linked with the nuclear localization of redox sensitive transcription factors, as Nrf2 and NF-κB, and with the differentiation potential. Taken together, these results suggest that nNox4 regulation may have important effects in stem cell capability through modulation of transcription factors and DNA damage. Tullia Maraldi, Marianna Guida, Manuela Zavatti, Elisa Resca, Laura Bertoni, Giovanni B. La Sala, and Anto De Pol Copyright © 2015 Tullia Maraldi et al. All rights reserved. GC-Rich Extracellular DNA Induces Oxidative Stress, Double-Strand DNA Breaks, and DNA Damage Response in Human Adipose-Derived Mesenchymal Stem Cells Sun, 26 Jul 2015 08:23:04 +0000 http://www.hindawi.com/journals/omcl/2015/782123/ Background. Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases. CfDNA is substantially enriched in its GC-content as compared with human genomic DNA. Principal Findings. Exposure of haMSCs to GC-DNA induces short-term oxidative stress (determined with H2DCFH-DA) and results in both single- and double-strand DNA breaks (comet assay and γH2AX, foci). As a result in the cells significantly increases the expression of repair genes (BRCA1 (RT-PCR), PCNA (FACS)) and antiapoptotic genes (BCL2 (RT-PCR and FACS), BCL2A1, BCL2L1, BIRC3, and BIRC2 (RT-PCR)). Under the action of GC-DNA the potential of mitochondria was increased. Here we show that GC-rich extracellular DNA stimulates adipocyte differentiation of human adipose-derived mesenchymal stem cells (haMSCs). Exposure to GC-DNA leads to an increase in the level of RNAPPARG2 and LPL (RT-PCR), in the level of fatty acid binding protein FABP4 (FACS analysis) and in the level of fat (Oil Red O). Conclusions. GC-rich fragments in the pool of cfDNA can potentially induce oxidative stress and DNA damage response and affect the direction of mesenchymal stem cells differentiation in human adipose—derived mesenchymal stem cells. Such a response may be one of the causes of obesity or osteoporosis. Svetlana Kostyuk, Tatiana Smirnova, Larisa Kameneva, Lev Porokhovnik, Anatolij Speranskij, Elizaveta Ershova, Sergey Stukalov, Vera Izevskaya, and Natalia Veiko Copyright © 2015 Svetlana Kostyuk et al. All rights reserved. Increased Oxidative Stress as a Selective Anticancer Therapy Sun, 26 Jul 2015 08:22:22 +0000 http://www.hindawi.com/journals/omcl/2015/294303/ Reactive oxygen species (ROS) are closely related to tumorgenesis. Under hypoxic environment, increased levels of ROS induce the expression of hypoxia inducible factors (HIFs) in cancer stem cells (CSCs), resulting in the promotion of the upregulation of CSC markers, and the reduction of intracellular ROS level, thus facilitating CSCs survival and proliferation. Although the ROS level is regulated by powerful antioxidant defense mechanisms in cancer cells, it is observed to remain higher than that in normal cells. Cancer cells may be more sensitive than normal cells to the accumulation of ROS; consequently, it is supposed that increased oxidative stress by exogenous ROS generation therapy has an effect on selectively killing cancer cells without affecting normal cells. This paper reviews the mechanisms of redox regulation in CSCs and the pivotal role of ROS in anticancer treatment. Jiahui Liu and Zhichong Wang Copyright © 2015 Jiahui Liu and Zhichong Wang. All rights reserved. Reactive Oxygen Species in Mesenchymal Stem Cell Aging: Implication to Lung Diseases Sun, 26 Jul 2015 08:13:08 +0000 http://www.hindawi.com/journals/omcl/2015/486263/ MSCs have become an emerging cell source with their immune modulation, high proliferation rate, and differentiation potential; indeed, they have been challenged in clinical trials. Recently, it has shown that ROS play a dual role as both deleterious and beneficial species depending on their concentration in MSCs. Various environmental stresses-induced excessive production of ROS triggers cellular senescence and abnormal differentiation on MSCs. Moreover, MSCs have been suggested to participate in the treatment of ALI/ARDS and COPD as a major cause of high morbidity and mortality. Therapeutic mechanisms of MSCs in the treatment of ARDS/COPD were focused on cell engraftment and paracrine action. However, ROS-mediated therapeutic mechanisms of MSCs still remain largely unknown. Here, we review the key factors associated with cell cycle and chromatin remodeling to accelerate or delay the MSC aging process. In addition, the enhanced ROS production and its associated pathophysiological pathways will be discussed along with the MSC senescence process. Furthermore, the present review highlights how the excessive amount of ROS-mediated oxidative stress might interfere with homeostasis of lungs and residual lung cells in the pathogenesis of ALI/ARDS and COPD. Se-Ran Yang, Jeong-Ran Park, and Kyung-Sun Kang Copyright © 2015 Se-Ran Yang et al. All rights reserved. Isoflavones Reduce Copper with Minimal Impact on Iron In Vitro Sun, 26 Jul 2015 06:37:10 +0000 http://www.hindawi.com/journals/omcl/2015/437381/ Isoflavones are commonly consumed in many Asian countries and have potentially positive effects on human being. Only a few and rather controversial data on their interactions with copper and iron are available to date. 13 structurally related isoflavones were tested in the competitive manner for their Cu/Fe-chelating/reducing properties. Notwithstanding the 5-hydroxy-4-keto chelation site was associated with ferric, ferrous, and cupric chelation, the chelation potential of isoflavones was low and no cuprous chelation was observed. None of isoflavones was able to substantially reduce ferric ions, but the vast majority reduced cupric ions. The most important feature for cupric reduction was the presence of an unsubstituted 4′-hydroxyl; contrarily the presence of a free 5-hydroxyl decreased or abolished the reduction due to chelation of cupric ions. The results from this study may enable additional experiments which might clarify the effects of isoflavones on human being and/or mechanisms of copper absorption. Jana Karlíčková, Kateřina Macáková, Michal Říha, Liliane Maria Teixeira Pinheiro, Tomáš Filipský, Veronika Horňasová, Radomír Hrdina, and Přemysl Mladěnka Copyright © 2015 Jana Karlíčková et al. All rights reserved. Oxidative Stress-Mediated Reperfusion Injury 2014 Wed, 22 Jul 2015 12:16:48 +0000 http://www.hindawi.com/journals/omcl/2015/689416/ Zhengyuan Xia, Yanfang Chen, Qian Fan, Mengzhou Xue, and Ke-xuan Liu Copyright © 2015 Zhengyuan Xia et al. All rights reserved. Protective Effects of Kaempferol against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart via Antioxidant Activity and Inhibition of Glycogen Synthase Kinase-3 Wed, 22 Jul 2015 06:55:45 +0000 http://www.hindawi.com/journals/omcl/2015/481405/ Objective. This study aimed to evaluate the protective effect of kaempferol against myocardial ischemia/reperfusion (I/R) injury in rats. Method. Left ventricular developed pressure (LVDP) and its maximum up/down rate () were recorded as myocardial function. Infarct size was detected with 2,3,5-triphenyltetrazolium chloride staining. Cardiomyocyte apoptosis was determined using terminal deoxynucleotidyl nick-end labeling (TUNEL). The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-α) were determined using enzyme linked immunosorbent assay (ELISA). Moreover, total glycogen synthase kinase-3β (GSK-3β), phospho-GSK-3β (P-GSK-3β), precaspase-3, cleaved caspase-3, and cytoplasm cytochrome C were assayed using Western blot analysis. Results. Pretreatment with kaempferol significantly improved the recovery of LVDP and , as well as increased the levels of SOD and P-GSK-3β and GSH/GSSG ratio. However, the pretreatment reduced myocardial infarct size and TUNEL-positive cell rate, as well as decreased the levels of cleaved caspase-3, cytoplasm cytochrome C, CK, LDH, MDA, and TNF-α. Conclusion. These results suggested that kaempferol provides cardioprotection via antioxidant activity and inhibition of GSK-3β activity in rats with I/R. Mingjie Zhou, Huanhuan Ren, Jichun Han, Wenjuan Wang, Qiusheng Zheng, and Dong Wang Copyright © 2015 Mingjie Zhou et al. All rights reserved. Daily Oxygen/O3 Treatment Reduces Muscular Fatigue and Improves Cardiac Performance in Rats Subjected to Prolonged High Intensity Physical Exercise Tue, 21 Jul 2015 12:32:42 +0000 http://www.hindawi.com/journals/omcl/2015/190640/ Rats receiving daily intraperitoneal administration of O2 and running on a treadmill covered an average distance of 482.8 ± 21.8 m/week as calculated during 5-week observation. This distance was increased in rats receiving daily intraperitoneal administration of an oxygen/O3 mixture at a dose of 100; 150; and 300 μg/kg with the maximum increase being +34.5% at 300 μg/kg and still present after stopping the administration of oxygen/O3. Oxygen/O3 decreased the mean arterial blood pressure (−13%), the heart rate (−6%), the gastrocnemius and cardiac hypertrophy, and fibrosis and reduced by 49% the left ventricular mass and relative wall thickness measurements. Systolic and diastolic functions were improved in exercised oxygen/O3 rats compared to O2 rats. Oxygen/O3 treatment led to higher MPI index starting from the dose of 150 μg/kg () and more effective (+14%) at a dose of 300 μg/kg oxygen/O3. Oxygen/O3 dose-dependently increased the expression of the antioxidant enzymes Mn-SOD and GPx1 and of eNOS compared to the exercised O2 rats. The same doses resulted in decrease of LDH levels, CPK, TnI, and nitrotyrosine concentration in the heart and gastrocnemius tissues, arguing a beneficial effect of the ozone molecule against the fatigue induced by a prolonged high intensity exercise. C. Di Filippo, M. C. Trotta, R. Maisto, D. Siniscalco, M. Luongo, L. Mascolo, R. Alfano, M. Accardo, C. Rossi, F. Ferraraccio, and M. D’Amico Copyright © 2015 C. Di Filippo et al. All rights reserved. Dietary Polyphenols and Their Effects on Cell Biochemistry and Pathophysiology 2014 Tue, 21 Jul 2015 11:34:22 +0000 http://www.hindawi.com/journals/omcl/2015/782424/ Cristina Angeloni, Tullia Maraldi, Dragan Milenkovic, and David Vauzour Copyright © 2015 Cristina Angeloni et al. All rights reserved. Plant Natural Products Calycosin and Gallic Acid Synergistically Attenuate Neutrophil Infiltration and Subsequent Injury in Isoproterenol-Induced Myocardial Infarction: A Possible Role for Leukotriene B4 12-Hydroxydehydrogenase? Tue, 21 Jul 2015 09:19:48 +0000 http://www.hindawi.com/journals/omcl/2015/434052/ Leukotriene B4 12-hydroxydehydrogenase (LTB4DH) catalyzes the oxidation of proinflammatory LTB4 into less bioactive 12-oxo-LTB4. We recently discovered that LTB4DH was induced by two different natural products in combination. We previously isolated gallic acid from Radix Paeoniae through a bioactivity-guided fractionation procedure. The purpose of this study is to test the hypothesis that LTB4DH inducers may suppress neutrophil-mediated inflammation in myocardial infarction. We first isolated the active compound(s) from another plant, Radix Astragali, by the similar strategy. By evaluating LTB4DH induction, we identified calycosin and formononetin from Radix Astragali by HPLC-ESI-MS technique. We confirmed that gallic acid and commercial calycosin or formononetin could synergistically induce LTB4DH expression in HepG2 cells and human neutrophils. Moreover, calycosin and gallic acid attenuated the effects of LTB4 on the survival and chemotaxis of neutrophil cell culture. We further demonstrated that calycosin and gallic acid synergistically suppressed neutrophil infiltration and protected cardiac integrity in the isoproterenol-induced mice model of myocardial infarction. Calycosin and gallic acid dramatically suppressed isoproterenol-induced increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) level. Collectively, our results suggest that LTB4DH inducers (i.e., calycosin and gallic acid) may be a novel combined therapy for the treatment of neutrophil-mediated myocardial injury. Yuanyuan Cheng, Jia Zhao, Hung Fat Tse, X. Chris Le, and Jianhui Rong Copyright © 2015 Yuanyuan Cheng et al. All rights reserved. Molecular Events Linking Oxidative Stress and Inflammation to Insulin Resistance and β-Cell Dysfunction Tue, 14 Jul 2015 12:35:23 +0000 http://www.hindawi.com/journals/omcl/2015/181643/ The prevalence of diabetes mellitus (DM) is increasing worldwide, a consequence of the alarming rise in obesity and metabolic syndrome (MetS). Oxidative stress and inflammation are key physiological and pathological events linking obesity, insulin resistance, and the progression of type 2 DM (T2DM). Unresolved inflammation alongside a “glucolipotoxic” environment of the pancreatic islets, in insulin resistant pathologies, enhances the infiltration of immune cells which through secretory activity cause dysfunction of insulin-secreting β-cells and ultimately cell death. Recent molecular investigations have revealed that mechanisms responsible for insulin resistance associated with T2DM are detected in conditions such as obesity and MetS, including impaired insulin receptor (IR) signalling in insulin responsive tissues, oxidative stress, and endoplasmic reticulum (ER) stress. The aim of the present review is to describe the evidence linking oxidative stress and inflammation with impairment of insulin secretion and action, which result in the progression of T2DM and other conditions associated with metabolic dysregulation. Kevin Noel Keane, Vinicius Fernandes Cruzat, Rodrigo Carlessi, Paulo Ivo Homem de Bittencourt Jr., and Philip Newsholme Copyright © 2015 Kevin Noel Keane et al. All rights reserved. Brewers’ Rice: A By-Product from Rice Processing Provides Natural Hepatorenal Protection in Azoxymethane-Induced Oxidative Stress in Rats Tue, 14 Jul 2015 11:02:18 +0000 http://www.hindawi.com/journals/omcl/2015/539798/ Brewers’ rice, which is known locally as temukut, is a mixture of broken rice, rice bran, and rice germ. Our present study was designed to identify the effect of brewers’ rice on the attenuation of liver and kidney damage induced by azoxymethane (AOM). Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), creatinine, and urea were evaluated to understand potential hepatoprotective effects and the ability of brewers’ rice to attenuate kidney pathology induced by AOM treatment. Liver and kidney tissues were evaluated by hematoxylin and eosin (H&E) staining. Overall analyses revealed that brewers’ rice improved the levels of serum markers in a manner associated with better histopathological outcomes, which indicated that brewers’ rice could enhance recovery from hepatocyte and kidney damage. Taken together, these results suggest that brewers’ rice could be used in future applications to combat liver and kidney disease. Bee Ling Tan, Mohd Esa Norhaizan, Ithnin Hairuszah, Hamzah Hazilawati, and Karim Roselina Copyright © 2015 Bee Ling Tan et al. All rights reserved. Chlorpyrifos Induces the Expression of the Epstein-Barr Virus Lytic Cycle Activator BZLF-1 via Reactive Oxygen Species Tue, 14 Jul 2015 06:45:04 +0000 http://www.hindawi.com/journals/omcl/2015/309125/ Organophosphate pesticides (OPs) are among the most widely used synthetic chemicals for the control of a wide variety of pests, and reactive oxygen species (ROS) caused by OPs may be involved in the toxicity of various pesticides. Previous studies have demonstrated that a reactivation of latent Epstein-Barr virus (EBV) could be induced by oxidative stress. In this study, we investigated whether OPs could reactivate EBV through ROS accumulation. The Raji cells were treated with chlorpyrifos (CPF), one of the most commonly used OPs. Oxidative stress indicators and the expression of the EBV immediate-early gene BZLF-1 were determined after CPF treatment. Our results show that CPF induces oxidative stress as evidenced by decreased malondialdehyde (MDA) level, accompanied by an increase in ROS production, DNA damage, glutathione (GSH) level, and superoxide dismutase (SOD) and catalase (CAT) activity. Moreover, CPF treatment significantly enhances the expression of BZLF-1, and the increased BZLF-1 expression was ameliorated by N-acetylcysteine (NAC) incubation. These results suggest that OPs could contribute to the reactivation of the EBV lytic cycle through ROS induction, a process that may play an important role in the development of EBV-associated diseases. Ling Zhao, Fei Xie, Ting-ting Wang, Meng-yu Liu, Jia-la Li, Lei Shang, Zi-xuan Deng, Peng-xiang Zhao, and Xue-mei Ma Copyright © 2015 Ling Zhao et al. All rights reserved. Propofol Attenuates Small Intestinal Ischemia Reperfusion Injury through Inhibiting NADPH Oxidase Mediated Mast Cell Activation Sun, 12 Jul 2015 10:22:44 +0000 http://www.hindawi.com/journals/omcl/2015/167014/ Both oxidative stress and mast cell (MC) degranulation participate in the process of small intestinal ischemia reperfusion (IIR) injury, and oxidative stress induces MC degranulation. Propofol, an anesthetic with antioxidant property, can attenuate IIR injury. We postulated that propofol can protect against IIR injury by inhibiting oxidative stress subsequent from NADPH oxidase mediated MC activation. Cultured RBL-2H3 cells were pretreated with antioxidant N-acetylcysteine (NAC) or propofol and subjected to hydrogen peroxide (H2O2) stimulation without or with MC degranulator compound 48/80 (CP). H2O2 significantly increased cells degranulation, which was abolished by NAC or propofol. MC degranulation by CP further aggravated H2O2 induced cell degranulation of small intestinal epithelial cell, IEC-6 cells, stimulated by tryptase. Rats subjected to IIR showed significant increases in cellular injury and elevations of NADPH oxidase subunits p and gp protein expression, increases of the specific lipid peroxidation product 15--Isoprostane and interleukin-6, and reductions in superoxide dismutase activity with concomitant enhancements in tryptase and β-hexosaminidase. MC degranulation by CP further aggravated IIR injury. And all these changes were attenuated by NAC or propofol pretreatment, which also abrogated CP-mediated exacerbation of IIR injury. It is concluded that pretreatment of propofol confers protection against IIR injury by suppressing NADPH oxidase mediated MC activation. Xiaoliang Gan, Dandan Xing, Guangjie Su, Shun Li, Chenfang Luo, Michael G. Irwin, Zhengyuan Xia, Haobo Li, and Ziqing Hei Copyright © 2015 Xiaoliang Gan et al. All rights reserved. The Effect of Age on Osteogenic and Adipogenic Differentiation Potential of Human Adipose Derived Stromal Stem Cells (hASCs) and the Impact of Stress Factors in the Course of the Differentiation Process Sun, 12 Jul 2015 09:35:23 +0000 http://www.hindawi.com/journals/omcl/2015/309169/ Human adipose tissue is a great source of autologous mesenchymal stem cells (hASCs), which are recognized for their vast therapeutic applications. Their ability to self-renew and differentiate into several lineages makes them a promising tool for cell-based therapies in different types of degenerative diseases. Thus it is crucial to evaluate age-related changes in hASCs, as the elderly are a group that will benefit most from their considerable potential. In this study we investigated the effect of donor age on growth kinetics, cellular senescence marker levels, and osteogenic and adipogenic potential of hASCs. It also has been known that, during life, organisms accumulate oxidative damage that negatively affects cell metabolism. Taking this into consideration, we evaluated the levels of nitric oxide, reactive oxygen species, and superoxide dismutase activity. We observed that ROS and NO increase with aging, while SOD activity is significantly reduced. Moreover cells obtained from older patients displayed senescence associated features, for example, β-galactosidase activity, enlarged morphology, and p53 protein upregulation. All of those characteristics seem to contribute to decreased proliferation potential of those cells. Our results suggest that due to aging some cellular modification may be required before applying aged cells efficiently in therapies such as tissue engineering and regenerative medicine. Katarzyna Kornicka, Krzysztof Marycz, Krzysztof Andrzej Tomaszewski, Monika Marędziak, and Agnieszka Śmieszek Copyright © 2015 Katarzyna Kornicka et al. All rights reserved. Ginkgolide B Inhibits JAM-A, Cx43, and VE-Cadherin Expression and Reduces Monocyte Transmigration in Oxidized LDL-Stimulated Human Umbilical Vein Endothelial Cells Sun, 12 Jul 2015 09:29:08 +0000 http://www.hindawi.com/journals/omcl/2015/907926/ Aim. To investigate the effect of ginkgolide B on junction proteins and the reduction of monocyte migration in oxidized low-density lipoprotein- (ox-LDL-) treated endothelial cells. Methods. Human umbilical vein endothelial cells (HUVECs) were used in the present study. Immunofluorescence and Western blot were performed to determine the expression of junctional adhesion molecule-A (JAM-A), connexin 43 (Cx43), and vascular endothelial cadherin (VE-cadherin). Monocyte migration was detected by the Transwell assay. Results. ox-LDL stimulation increased JAM-A expression by 35%, Cx43 expression by 24%, and VE-cadherin expression by 37% in HUVECs. Ginkgolide B (0.2, 0.4, and 0.6 mg/mL) dose-dependently abolished the expression of these junction proteins. The monocyte transmigration experiments showed that the level of monocyte migration was sixfold higher in the ox-LDL-treated group than in the control group. Ginkgolide B (0.6 mg/mL) nearly completely abolished monocyte migration. Both ginkgolide B and LY294002 suppressed Akt phosphorylation and the expression of these junction proteins in ox-LDL-treated endothelial cells. These results suggest that the ginkgolide B-induced inhibition of junction protein expression is associated with blockade of the PI3K/Akt pathway. Conclusion. Ginkgolide B suppressed junction protein expression and reduced monocyte transmigration that was induced by ox-LDL. Ginkgolide B may improve vascular permeability in atherosclerosis. Xueqing Liu, Wenjia Sun, Yanyang Zhao, Beidong Chen, Wei Wu, Li Bao, and Ruomei Qi Copyright © 2015 Xueqing Liu et al. All rights reserved. Dietary Antioxidant and Flavonoid Intakes Are Reduced in the Elderly Wed, 08 Jul 2015 10:32:02 +0000 http://www.hindawi.com/journals/omcl/2015/843173/ The objective of this study was to determine sources and patterns of antioxidant and flavonoid intakes in the elderly (61–74 yrs) in comparison with young (20–40 yrs) and middle age (41–60 yrs) groups in a cross-sectional study. More than 6000 subjects of both genders, aged 20–74 years, participants of the National Multicenter Health Survey (WOBASZ) took part in this study. Daily food consumption was estimated by the single 24-hour dietary recall. Dietary total antioxidant capacity (TAC) and flavonoid content (FC) were calculated according to the amount of food consumed by the participants combined with antioxidant capacity and flavonoid contents in foods. Food consumption, dietary TAC, and FC were significantly lower in the elderly, especially elderly women in comparison to the young and middle age groups. The consumption of tea, coffee, and apples was associated with the largest contribution to dietary TAC and FC in all participants. Despite high nutrient density of the energy-adjusted diet of ageing people, the elderly consumed the lowest amounts of antioxidants and flavonoids due to the lowest food intake. Małgorzata Elżbieta Zujko, Anna Maria Witkowska, Anna Waśkiewicz, and Iwona Mirończuk-Chodakowska Copyright © 2015 Małgorzata Elżbieta Zujko et al. All rights reserved. Cytokine Dysregulation in MECP2- and CDKL5-Related Rett Syndrome: Relationships with Aberrant Redox Homeostasis, Inflammation, and ω-3 PUFAs Wed, 08 Jul 2015 06:54:26 +0000 http://www.hindawi.com/journals/omcl/2015/421624/ An involvement of the immune system has been suggested in Rett syndrome (RTT), a devastating neurodevelopmental disorder related to oxidative stress, and caused by a mutation in the methyl-CpG binding protein 2 gene (MECP2) or, more rarely, cyclin-dependent kinase-like 5 (CDKL5). To date, it is unclear whether both mutations may have an impact on the circulating cytokine patterns. In the present study, cytokines involved in the Th1-, Th2-, and T regulatory (T-reg) response, as well as chemokines, were investigated in MECP2- (MECP2-RTT) () and CDKL5-Rett syndrome (CDKL5-RTT) (), before and after ω-3 polyunsaturated fatty acids (PUFAs) supplementation. A major cytokine dysregulation was evidenced in untreated RTT patients. In MECP2-RTT, a Th2-shifted balance was evidenced, whereas in CDKL5-RTT both Th1- and Th2-related cytokines (except for IL-4) were upregulated. In MECP2-RTT, decreased levels of IL-22 were observed, whereas increased IL-22 and T-reg cytokine levels were evidenced in CDKL5-RTT. Chemokines were unchanged. The cytokine dysregulation was proportional to clinical severity, inflammatory status, and redox imbalance. Omega-3 PUFAs partially counterbalanced cytokine changes, as well as aberrant redox homeostasis and the inflammatory status. RTT is associated with a subclinical immune dysregulation as the likely consequence of a defective inflammation regulatory signaling system. Silvia Leoncini, Claudio De Felice, Cinzia Signorini, Gloria Zollo, Alessio Cortelazzo, Thierry Durand, Jean-Marie Galano, Roberto Guerranti, Marcello Rossi, Lucia Ciccoli, and Joussef Hayek Copyright © 2015 Silvia Leoncini et al. All rights reserved. Neuroprotection by Cocktails of Dietary Antioxidants under Conditions of Nerve Growth Factor Deprivation Wed, 08 Jul 2015 06:20:54 +0000 http://www.hindawi.com/journals/omcl/2015/217258/ Dietary antioxidants may be useful in counteracting the chronic inflammatory status in neurodegenerative diseases by reducing oxidative stress due to accumulation of reactive oxygen species (ROS). In this study, we newly described the efficacy of a number of dietary antioxidants (polyphenols, carotenoids, thiolic compounds, and oligoelements) on viability of neuronal PC12 cells following Nerve Growth Factor (NGF) deprivation, a model of age-related decrease of neurotrophic support that triggers neuronal loss. Neuroprotection by antioxidants during NGF deprivation for 24 h was largely dependent on their concentrations: all dietary antioxidants were able to efficiently support cell viability by reducing ROS levels and restoring mitochondrial function, while preserving the neuronal morphology. Moreover, ROS reduction and neuroprotection during NGF withdrawal were also achieved with defined cocktails of 3–6 different antioxidants at concentrations 5–60 times lower than those used in single treatments, suggesting that their antioxidant activity was preserved also at very low concentrations. Overall, these data indicate the beneficial effects of antioxidants against oxidative stress induced by decreased NGF availability and suggest that defined cocktails of dietary factors at low concentrations might be a suitable strategy to reduce oxidative damage in neurodegenerative diseases, while limiting possible side effects. Flavio Amara, Miluscia Berbenni, Martina Fragni, Giampaolo Leoni, Sandra Viggiani, Vita Maria Ippolito, Marilena Larocca, Rocco Rossano, Lilia Alberghina, Paolo Riccio, and Anna Maria Colangelo Copyright © 2015 Flavio Amara et al. All rights reserved. Carqueja (Baccharis trimera) Protects against Oxidative Stress and β-Amyloid-Induced Toxicity in Caenorhabditis elegans Tue, 07 Jul 2015 11:22:08 +0000 http://www.hindawi.com/journals/omcl/2015/740162/ Carqueja (Baccharis trimera) is a native plant found throughout South America. Several studies have shown that Carqueja has antioxidant activity in vitro, as well as anti-inflammatory, antidiabetic, analgesic, antihepatotoxic, and antimutagenic properties. However, studies regarding its antioxidant potential in vivo are limited. In this study, we used Caenorhabditis elegans as a model to examine the antioxidant effects of a Carqueja hydroalcoholic extract (CHE) on stress resistance and lifespan and to investigate whether CHE has a protective effect in a C. elegans model for Alzheimer's disease. Here, we show for the first time, using in vivo assays, that CHE treatment improved oxidative stress resistance by increasing survival rate and by reducing ROS levels under oxidative stress conditions independently of the stress-related signaling pathways (p38, JNK, and ERK) and transcription factors (SKN-1/Nrf and DAF-16/Foxo) tested here. CHE treatment also increased the defenses against β-amyloid toxicity in C. elegans, in part by increasing proteasome activity and the expression of two heat shock protein genes. Our findings suggest a potential neuroprotective use for Carqueja, supporting the idea that dietary antioxidants are a promising approach to boost the defensive systems against stress and neurodegeneration. Franciny Aparecida Paiva, Larissa de Freitas Bonomo, Patrícia Ferreira Boasquivis, Igor Thadeu Borges Raposo de Paula, Joyce Ferreira da Costa Guerra, Wagney Mendes Leal, Marcelo Eustáquio Silva, Maria Lúcia Pedrosa, and Riva de Paula Oliveira Copyright © 2015 Franciny Aparecida Paiva et al. All rights reserved. The Effect of Etoricoxib on Hepatic Ischemia-Reperfusion Injury in Rats Sun, 05 Jul 2015 12:12:20 +0000 http://www.hindawi.com/journals/omcl/2015/598162/ Ischemia-reperfusion (I/R) damage is known to be a pathological process which continues with the increase of oxidants and expands with the inflammatory response. There is not any study about protective effect of etoricoxib on the liver I/R damage in literature. Objective. This study investigates the effect of etoricoxib on oxidative stress induced by I/R of the rat liver. Material and Methods. Experimental animals were divided into four groups as liver I/R control (LIRC), 50 mg/kg etoricoxib + liver I/R (ETO-50), 100 mg/kg etoricoxib + liver I/R (ETO-100), and healthy group (HG). ETO-50 and ETO-100 groups were administered etoricoxib, while LIRC and HG groups were orally given distilled water by gavage. Hepatic artery was clamped for one hour to provide ischemia, and then reperfusion was provided for 6 hours. Oxidant, antioxidant, and COX-2 gene expressions were studied in the liver tissues. ALT and AST were measured. Results. Etoricoxib in 50 and 100 mg/kg doses changed the levels of oxidant/antioxidant parameters such as MDA, MPO, tGSH, GSHRd, GST, SOD, NO, and 8-OH/Gua in favour of antioxidants. Furthermore, etoricoxib prevented increase of COX-2 gene expression and ALT and AST levels. This important protective effect of etoricoxib on the rat liver I/R can be tested in the clinical setting. Celalettin Semih Kunak, Osman Kukula, Emre Mutlu, Fatma Genç, Gülçer Güleç Peker, Ufuk Kuyrukluyıldız, Orhan Binici, Durdu Altuner, and Hamit Hakan Alp Copyright © 2015 Celalettin Semih Kunak et al. All rights reserved. High Potency of a Novel Resveratrol Derivative, 3,3′,4,4′-Tetrahydroxy-trans-stilbene, against Ovarian Cancer Is Associated with an Oxidative Stress-Mediated Imbalance between DNA Damage Accumulation and Repair Wed, 01 Jul 2015 12:30:28 +0000 http://www.hindawi.com/journals/omcl/2015/135691/ We explored the effect of a new resveratrol (RVT) derivative, 3,3′,4,4′-tetrahydroxy-trans-stilbene (3,3′,4,4′-THS), on viability, apoptosis, proliferation, and senescence of three representative lines of ovarian cancer cells, that is, A2780, OVCAR-3, and SKOV-3, in vitro. In addition, the mechanistic aspects of 3,3′,4,4′-THS activity, including cell redox homeostasis (the production of reactive oxygen species, activity of enzymatic antioxidants, and magnitude of DNA damage accumulation and repair), and the activity of caspases (3, 8, and 9) and p38 MAPK were examined. The study showed that 3,3′,4,4′-THS affects cancer cell viability much more efficiently than its parent drug. This effect coincided with increased generation of reactive oxygen species, downregulated activity of superoxide dismutase and catalase, and excessive accumulation of 8-hydroxy-2′-deoxyguanosine and its insufficient repair due to decreased expression of DNA glycosylase I. Cytotoxicity elicited by 3,3′,4,4′-THS was related to increased incidence of apoptosis, which was mediated by caspases 3 and 9. Moreover, 3,3′,4,4′-THS inhibited cancer cell proliferation and accelerated senescence, which was accompanied by the activation of p38 MAPK. Collectively, our findings indicate that 3,3′,4,4′-THS may constitute a valuable tool in the fight against ovarian malignancy and that the anticancer capabilities of this stilbene proceed in an oxidative stress-dependent mechanism. Justyna Mikuła-Pietrasik, Patrycja Sosińska, Marek Murias, Marcin Wierzchowski, Marta Brewińska-Olchowik, Katarzyna Piwocka, Dariusz Szpurek, and Krzysztof Książek Copyright © 2015 Justyna Mikuła-Pietrasik et al. All rights reserved. Mitochondrial Dysfunction Contributes to the Pathogenesis of Alzheimer’s Disease Mon, 29 Jun 2015 08:29:59 +0000 http://www.hindawi.com/journals/omcl/2015/509654/ Alzheimer’s disease (AD) is a neurodegenerative disease that affects millions of people worldwide. Currently, there is no effective treatment for AD, which indicates the necessity to understand the pathogenic mechanism of this disorder. Extracellular aggregates of amyloid precursor protein (APP), called Aβ peptide and neurofibrillary tangles (NFTs), formed by tau protein in the hyperphosphorylated form are considered the hallmarks of AD. Accumulative evidence suggests that tau pathology and Aβ affect neuronal cells compromising energy supply, antioxidant response, and synaptic activity. In this context, it has been showed that mitochondrial function could be affected by the presence of tau pathology and Aβ in AD. Mitochondria are essential for brain cells function and the improvement of mitochondrial activity contributes to preventing neurodegeneration. Several reports have suggested that mitochondria could be affected in terms of morphology, bioenergetics, and transport in AD. These defects affect mitochondrial health, which later will contribute to the pathogenesis of AD. In this review, we will discuss evidence that supports the importance of mitochondrial injury in the pathogenesis of AD and how studying these mechanisms could lead us to suggest new targets for diagnostic and therapeutic intervention against neurodegeneration. Fabian A. Cabezas-Opazo, Katiana Vergara-Pulgar, María José Pérez, Claudia Jara, Cesar Osorio-Fuentealba, and Rodrigo A. Quintanilla Copyright © 2015 Fabian A. Cabezas-Opazo et al. All rights reserved. Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans Sun, 28 Jun 2015 14:20:48 +0000 http://www.hindawi.com/journals/omcl/2015/837042/ Plants containing resveratrol have been used effectively in traditional medicine for over 2000 years. It can be found in some plants, fruits, and derivatives, such as red wine. Therefore, it can be administered by either consuming these natural products or intaking nutraceutical pills. Resveratrol exhibits a wide range of beneficial properties, and this may be due to its molecular structure, which endow resveratrol with the ability to bind to many biomolecules. Among these properties its activity as an anticancer agent, a platelet antiaggregation agent, and an antioxidant, as well as its antiaging, antifrailty, anti-inflammatory, antiallergenic, and so forth activities, is worth highlighting. These beneficial biological properties have been extensively studied in humans and animal models, both in vitro and in vivo. The issue of bioavailability of resveratrol is of paramount importance and is determined by its rapid elimination and the fact that its absorption is highly effective, but the first hepatic step leaves little free resveratrol. Clarifying aspects like stability and pharmacokinetics of resveratrol metabolites would be fundamental to understand and apply the therapeutic properties of resveratrol. J. Gambini, M. Inglés, G. Olaso, R. Lopez-Grueso, V. Bonet-Costa, L. Gimeno-Mallench, C. Mas-Bargues, K. M. Abdelaziz, M. C. Gomez-Cabrera, J. Vina, and C. Borras Copyright © 2015 J. Gambini et al. All rights reserved. Calcium Channel Blockers, Progression to Dementia, and Effects on Amyloid Beta Peptide Production Sun, 28 Jun 2015 11:26:46 +0000 http://www.hindawi.com/journals/omcl/2015/787805/ Previous epidemiologic studies suggest that antihypertensive drugs may be protective against cognitive decline. To determine if subjects enrolled in the University of Kentucky longitudinal aging study who used antihypertensive drugs showed diminished progression to dementia, we used a 3-parameter logistic regression model to compare the rate of progression to dementia for subjects who used any of the five common categories of antihypertensive drugs to those with similar demographic characteristics but who did not use antihypertensives. Regression modeling showed that subjects who used calcium channel blockers (CCBs) but not the other classes of antihypertensives showed a significant decrease in the rate of progression to dementia. Significantly, use of CCBs ameliorated the negative effects of the presence of APOE-4 alleles on cognitive decline. To determine if CCBs could minimize amyloid beta peptide (Aβ1–42) production, H4 neuroglioma cultures transfected to overexpress APP were treated with various CCBs and Aβ1–42 levels and levels of proteins involved in Aβ production were quantified. Results show that treatment with nifedipine led to a significant decrease in levels of Aβ1–42, with no significant decrease in cell viability. Collectively, these data suggest that use of CCBs significantly diminishes the rate of progression to dementia and may minimize formation of Aβ1–42. Mark A. Lovell, Erin Abner, Richard Kryscio, Liou Xu, Shuling X. Fister, and Bert C. Lynn Copyright © 2015 Mark A. Lovell et al. All rights reserved.