Oxidative Medicine and Cellular Longevity https://www.hindawi.com The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Antigenotoxic Properties of Agaricus blazei against Hydrogen Peroxide in Human Peripheral Blood Cells Tue, 21 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/8759764/ The ability of Agaricus blazei mushroom in its dried and powdered mycelial form was evaluated for its antigenotoxic properties for the first time. Antigenotoxic effects in human peripheral blood cells against H2O2-induced DNA damage were examined in pretreatment and posttreatment protocol by comet assay. The results showed better antigenotoxic properties of Agaricus blazei on the interventional level, respectively, after treatment. Agaricus blazei in concentration of 250 μg/mL after treatment was most efficient in regard to its action against DNA damage. The evaluation of repair kinetics showed decrease in H2O2 induced DNA damage 15 min after the application of A. blazei, reaching the maximum potency after 30 min. Analysis of antioxidant properties of Agaricus blazei revealed strong scavenging properties and moderate reducing power, while its DPPH scavenging ability was weak. In regard to our findings, we can conclude that our preliminary results demonstrated antigenotoxic properties of Agaricus blazei and its strong scavenging ability. Mechanisms underlying its properties should be further evaluated in in vivo studies. Lada Živković, Sunčica Borozan, Andrea Čabarkapa, Dijana Topalović, Ummi Ciptasari, Vladan Bajić, and Biljana Spremo-Potparević Copyright © 2017 Lada Živković et al. All rights reserved. TBHQ Alleviated Endoplasmic Reticulum Stress-Apoptosis and Oxidative Stress by PERK-Nrf2 Crosstalk in Methamphetamine-Induced Chronic Pulmonary Toxicity Mon, 20 Feb 2017 12:40:26 +0000 http://www.hindawi.com/journals/omcl/2017/4310475/ Methamphetamine (MA) leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS). The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ) alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA), and MA plus TBHQ-treated group (MA + TBHQ). Chronic exposure to MA resulted in slower growth of weight and pulmonary toxicity of the rats by increasing the pulmonary arterial pressure, promoting the hypertrophy of right ventricle and the remodeling of pulmonary arteries. MA inhibited the Nrf2-mediated antioxidative stress by downregulation of Nrf2, GCS, and HO-1 and upregulation of SOD2. MA increased GRP78 to induce ERS. Overexpression and phosphorylation of PERK rapidly phosphorylated eIF2α, increased ATF4, CHOP, bax, caspase 3, and caspase 12, and decreased bcl-2. These changes can be reversed by antioxidant TBHQ through upregulating expression of Nrf2. The above results indicated that TBHQ can alleviate MA-induced oxidative stress which can accelerate ERS to initiate PERK-dependent apoptosis and that PERK/Nrf2 is likely to be the key crosstalk between oxidative stress and ERS in MA-induced chronic pulmonary toxicity. Yun Wang, Yu-Han Gu, Ming Liu, Yang Bai, Li-Ye Liang, and Huai-Liang Wang Copyright © 2017 Yun Wang et al. All rights reserved. Diallyl Trisulfide Suppresses Oxidative Stress-Induced Activation of Hepatic Stellate Cells through Production of Hydrogen Sulfide Mon, 20 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/1406726/ Accumulating data reveal that garlic has beneficial effects against chronic liver disease. We previously reported that diallyl trisulfide (DATS), the primary organosulfur compound in garlic, reduced fibrosis and attenuated oxidative stress in rat fibrotic liver. The present study was aimed at elucidating the underlying mechanisms. The primary rat hepatic stellate cells (HSCs) were cultured and stimulated with hydrogen peroxide (H2O2) for inducing HSC activation under oxidative stress. We examined the effects of DATS on the profibrogenic properties and oxidative stress in H2O2-treated HSCs. The results showed that DATS suppressed and reduced fibrotic marker expression in HSCs. DATS arrested cell cycle at G2/M checkpoint associated with downregulating cyclin B1 and cyclin-dependent kinase 1, induced caspase-dependent apoptosis, and reduced migration in HSCs. Moreover, intracellular levels of reactive oxygen species and lipid peroxide were decreased by DATS, but intracellular levels of glutathione were increased in HSCs. Furthermore, DATS significantly elevated hydrogen sulfide (H2S) levels within HSCs, but iodoacetamide (IAM) reduced H2S levels and significantly abrogated DATS production of H2S within HSCs. IAM also abolished all the inhibitory effects of DATS on the profibrogenic properties and oxidative stress in HSCs. Altogether, we demonstrated an H2S-associated mechanism underlying DATS inhibition of profibrogenic properties and alleviation of oxidative stress in HSCs. Modulation of H2S production may represent a therapeutic remedy for liver fibrosis. Feng Zhang, Huanhuan Jin, Li Wu, Jiangjuan Shao, Xiaojing Zhu, Anping Chen, and Shizhong Zheng Copyright © 2017 Feng Zhang et al. All rights reserved. Carrageenan Based Bionanocomposites as Drug Delivery Tool with Special Emphasis on the Influence of Ferromagnetic Nanoparticles Mon, 20 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/8158315/ Over the past few years, considerable attention has been focused on carrageenan based bionanocomposites due to their multifaceted properties like biodegradability, biocompatibility, and nontoxicity. Moreover, these composites can be tailored according to the desired purpose by using different nanofillers. The role of ferromagnetic nanoparticles in drug delivery is also discussed here in detail. Moreover, this article also presents a short review of recent research on the different types of the carrageenan based bionanocomposites and applications. Abida Kalsoom Khan, Ain Us Saba, Shamyla Nawazish, Fahad Akhtar, Rehana Rashid, Sadullah Mir, Bushra Nasir, Furqan Iqbal, Samina Afzal, Fahad Pervaiz, and Ghulam Murtaza Copyright © 2017 Abida Kalsoom Khan et al. All rights reserved. Astragaloside IV for Experimental Focal Cerebral Ischemia: Preclinical Evidence and Possible Mechanisms Mon, 20 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/8424326/ Astragaloside IV (AST-IV) is a principal component of Radix Astragali seu Hedysari (Huangqi) and exerts potential neuroprotection in experimental ischemic stroke. Here, we systematically assessed the effectiveness and possible mechanisms of AST-IV for experimental acute ischemic stroke. An electronic search in eight databases was conducted from inception to March 2016. The study quality score was evaluated using the CAMARADES. Rev Man 5.0 software was used for data analyses. Thirteen studies with 244 animals were identified. The study quality score of included studies ranged from 3/10 to 8/10. Eleven studies showed significant effects of AST-IV for ameliorating the neurological function score (); seven studies for reducing the infarct volume (); and three or two studies for reducing the brain water content and Evans blue leakage (), respectively, compared with the control. The mechanisms of AST-IV for ischemic stroke are multiple such as antioxidative/nitration stress reaction, anti-inflammatory, and antiapoptosis. In conclusion, the findings of present study indicated that AST-IV could improve neurological deficits and infarct volume and reduce the blood-brain barrier permeability in experimental cerebral ischemia despite some methodological flaws. Thus, AST-IV exerted a possible neuroprotective effect during the cerebral ischemia/reperfusion injury largely through its antioxidant, anti-inflammatory, and antiapoptosis properties. Hui-Lin Wang, Qi-Hui Zhou, Meng-Bei Xu, Xiao-Li Zhou, and Guo-Qing Zheng Copyright © 2017 Hui-Lin Wang et al. All rights reserved. Cellular Preoxygenation Partially Attenuates the Antitumoral Effect of Cisplatin despite Highly Protective Effects on Renal Epithelial Cells Sun, 19 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/7203758/ Our previous in vitro studies demonstrated that oxygen pretreatment significantly protects human embryonic renal tubular cell against acute cisplatin- (CP-) induced cytotoxicity. The present study was designed to investigate whether this protective effect is associated with decreasing therapeutic effects of cisplatin on malignant cells. For this purpose, cultured human embryonic kidney epithelial-like (AD293), cervical carcinoma epithelial-like (Hela), and ovarian adenocarcinoma epithelial-like (OVCAR-3) cells were subjected to either 2-hour pretreatment with oxygen (≥90%) or normal air and then to a previously determined 50% lethal dose of cisplatin for 24 hours. Cellular viability was evaluated via MTT and Neutral Red assays. Also, activated caspase-3 and Bax/Bcl-2 ratio, as the biochemical markers of cell apoptosis, were determined using immunoblotting. The hyperoxic preexposure protocol significantly protects renal AD293 cells against cisplatin-induced toxicity. Oxygen pretreatment also partially attenuated the cisplatin-induced cytotoxic effects on Hela and OVCAR-3 cells. However, it did not completely protect these cells against the therapeutic cytotoxic effects of cisplatin. In summary, the protective methods for reducing cisplatin nephrotoxic side effects like oxygen pretreatment might be associated with concurrent reduction of the therapeutic cytotoxic effects of cisplatin on malignant cells like cervical carcinoma (Hela) and ovarian adenocarcinoma (OVCAR-3) cells. Bahram Rasoulian, Ayat Kaeidi, Maryam Rezaei, and Zahra Hajializadeh Copyright © 2017 Bahram Rasoulian et al. All rights reserved. Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia/Reperfusion Injury under Diabetes Sun, 19 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/6437467/ Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress. mTOR signaling presents both cardioprotective and cardiotoxic effects on the diabetic heart, which interplays with oxidative stress directly or indirectly. Antihyperglycemic agent metformin and newly found free radicals scavengers, Sirt1 and CTRP9, may serve as promising pharmacological therapeutic targets. In this review, we will focus on the role of oxidative stress and mTOR signaling in the pathophysiology of MI/R injury in diabetes and discuss potential mechanisms and their interactions in an effort to provide some evidence for cardiometabolic targeted therapies for ischemic heart disease (IHD). Dajun Zhao, Jian Yang, and Lifang Yang Copyright © 2017 Dajun Zhao et al. All rights reserved. A Review of mTOR Pathway Inhibitors in Gynecologic Cancer Mon, 13 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/4809751/ The treatment of advanced gynecologic cancers remains palliative in most of cases. Although systemic treatment has entered into the era of targeted drugs the antitumor efficacies of current therapies are still limited. In this context there is a great need for more active treatment and rationally designed targeted therapies. The PI3K/AKT/mTOR is a signaling pathway in mammal cells that coordinates important cell activities. It has a critical function in the survival, growth, and proliferation of malignant cells and was object of important research in the last two decades. The mTOR pathway emerges as an attractive therapeutic target in cancer because it serves as a convergence point for many growth stimuli and, through its downstream substrates, controls cellular processes that contribute to the initiation and maintenance of cancer. Aberrant PI3K-dependent signaling occurs frequently in a wide range of tumor types, including endometrial, cervical, and ovarian cancers. The present study reviewed the available evidence regarding the potential impact of some mTOR pathway inhibitors in the treatment of gynecological cancer. Few advances in medical management have occurred in recent years in the treatment of advanced or recurrent gynecological malignancies, and a poor prognosis remains. Rationally designed molecularly targeted therapy is an emerging and important option in this setting; then more investigation in PI3K/AKT/mTOR pathway-targeted therapies is warranted. Andréia Cristina de Melo, Eduardo Paulino, and Álvaro Henrique Ingles Garces Copyright © 2017 Andréia Cristina de Melo et al. All rights reserved. Influence of Synbiotics on Selected Oxidative Stress Parameters Mon, 13 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/9315375/ The aim of the present study was to assess synbiotic (Lactobacillus casei + inulin) influence on oxidative stress parameters such as concentrations of malondialdehyde (MDA), hydrogen peroxide (H2O2), glutathione, and free sulfhydryl groups content. Experiments were carried out on healthy volunteers (). The subjects were divided into women group () and men group () and randomly assigned to synbiotic and control groups. Blood samples were collected before synbiotic supplementation and after 7 wks, at the end of the study. The administration of synbiotic resulted in a significant decrease in MDA (), H2O2 (), and GSSG concentrations () as compared with the control groups and significant increase in the concentrations of GSHt (), GSH (), and -SH group content () versus control. Synbiotics containing L. casei plus inulin may have positive influence on selected oxidative stress markers. Paulina Kleniewska and Rafał Pawliczak Copyright © 2017 Paulina Kleniewska and Rafał Pawliczak. All rights reserved. Aspects of Carbon Monoxide in Form of CO-Releasing Molecules Used in Cancer Treatment: More Light on the Way Mon, 13 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/9326454/ Carbon monoxide (CO) has always been recognised as a toxic gas, due to its higher affinity for haemoglobin than oxygen. However, biological studies have revealed an intriguing role for CO as an endogenous signalling molecule, a gasotransmitter. CO is demonstrated to exert many cellular activities including anti-inflammatory, antiapoptotic, and antiproliferative activities. In animal studies, CO gas administration can prevent tissues from hypoxia or ischemic-reperfusion injury. As a result, there are a plethora of reports dealing with the biological applications of CO and CO-releasing molecules (CORMs) in inflammatory and vascular diseases. CORMs have already been tested as a therapeutic agent in clinical trials. More recently, an increased interest has been drawn to CO’s potential use as an anticancer agent. In this review, we will aim to give an overview of the research focused on the role of CO and CORMs in different types of cancer and expand to the recent development of the next generation CORMs for clinical application in cancer treatment. Malamati Kourti, Wen G. Jiang, and Jun Cai Copyright © 2017 Malamati Kourti et al. All rights reserved. Reactive Oxygen Species Mediated Prostaglandin E2 Contributes to Acute Response of Epithelial Injury Thu, 09 Feb 2017 13:58:18 +0000 http://www.hindawi.com/journals/omcl/2017/4123854/ Reactive oxygen species (ROS) generated after tissue injury play a crucial role during wound healing through initiating acute inflammation, clarifying infection and dead tissue, and mediating various intracellular signal transduction. Prostaglandin E2 (PGE2) has been identified as one of the major factors responsible for inflammation and tissue repair. In this study, we tested our hypothesis that ROS produced by damaged human keratinocytes induces the synthesis of PGE2. In vitro epithelial wounding model was used to observe the production of ROS and secretion of PGE2 as well as the involved signal pathway. The mechanical injury caused the rapid production of ROS in in vitro cultured keratinocytes, which was significantly blocked by an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase. The increased intracellular ROS caused by mechanical injury stimulates PGE2 production in a time-dependent manner via the activation of cyclooxygenase-2 (COX-2), which was stimulated by phosphorylation of extracellular signal-regulated protein kinase (ERK). These results indicate ROS-induced ERK activation leading to the activation of COX-2 and the synthesis of PGE2 in human keratinocytes responding to mechanical injury in the acute phase. Yi-Ping Hu, Yin-Bo Peng, Yi-Fan Zhang, Ying Wang, Wei-Rong Yu, Min Yao, and Xiu-Jun Fu Copyright © 2017 Yi-Ping Hu et al. All rights reserved. The Short Isoform of DNAJB6 Protects against 1-Methyl-4-phenylpridinium Ion-Induced Apoptosis in LN18 Cells via Inhibiting Both ROS Formation and Mitochondrial Membrane Potential Loss Thu, 09 Feb 2017 09:18:38 +0000 http://www.hindawi.com/journals/omcl/2017/7982389/ In a previous study, we found that the short isoform of DNAJB6 (DNAJB6(S)) had been decreased in the striatum of a mouse model of Parkinson’s disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). DNAJB6, one of the heat shock proteins, has been implicated in the pathogenesis of PD. In this study, we explored the cytoprotective effect of DNAJB6(S) against 1-methyl-4-phenylpyridinium ion- (MPP+-) induced apoptosis and the underlying molecular mechanisms in cultured LN18 cells from astrocytic tumors. We observed that MPP+ significantly reduced the cell viability and induced apoptosis in LN18 glioblastoma cells. DNAJB6(S) protected LN18 cells against MPP+-induced apoptosis not only by suppressing Bax cleavage but also by inhibiting a series of apoptotic events including loss of mitochondrial membrane potential, increase in intracellular reactive oxygen species, and activation of caspase-9. These observations suggest that the cytoprotective effects of DNAJB6(S) may be mediated, at least in part, by the mitochondrial pathway of apoptosis. Yeon-Mi Hong, Yohan Hong, Yeong-Gon Choi, Sujung Yeo, Soo Hee Jin, Sae-Won Lee, Backil Sung, Sook-Hyun Lee, Hyejin Jung, and Sabina Lim Copyright © 2017 Yeon-Mi Hong et al. All rights reserved. Resistance to mTORC1 Inhibitors in Cancer Therapy: From Kinase Mutations to Intratumoral Heterogeneity of Kinase Activity Thu, 09 Feb 2017 06:08:01 +0000 http://www.hindawi.com/journals/omcl/2017/1726078/ Targeting mTORC1 has been thoroughly explored in cancer therapy. Following encouraging preclinical studies, mTORC1 inhibitors however failed to provide substantial benefits in cancer patients. Several resistance mechanisms have been identified including mutations of mTOR and activation of alternate proliferation pathways. Moreover, emerging evidence discloses intratumoral heterogeneity of mTORC1 activity that further contributes to a reduced anticancer efficacy of mTORC1 inhibitors. Genetic heterogeneity as well as heterogeneous conditions of the tumor environment such as hypoxia profoundly modifies mTORC1 activity in tumors and hence influences the response of tumors to mTORC1 inhibitors. Intriguingly, the heterogeneity of mTORC1 activity also occurs towards its substrates at the single cell level, as mutually exclusive pattern of activation of mTORC1 downstream effectors has been reported in tumors. After briefly describing mTORC1 biology and the use of mTORC1 inhibitors in patients, this review will give an overview on concepts of resistance to mTORC1 inhibition in cancer with a particular focus on intratumoral heterogeneity of mTORC1 activity. Seraina Faes, Nicolas Demartines, and Olivier Dormond Copyright © 2017 Seraina Faes et al. All rights reserved. Resveratrol Attenuates Copper-Induced Senescence by Improving Cellular Proteostasis Thu, 09 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/3793817/ Copper sulfate-induced premature senescence (CuSO4-SIPS) consistently mimetized molecular mechanisms of replicative senescence, particularly at the endoplasmic reticulum proteostasis level. In fact, disruption of protein homeostasis has been associated to age-related cell/tissue dysfunction and human disorders susceptibility. Resveratrol is a polyphenolic compound with proved antiaging properties under particular conditions. In this setting, we aimed to evaluate resveratrol ability to attenuate cellular senescence induction and to unravel related molecular mechanisms. Using CuSO4-SIPS WI-38 fibroblasts, resveratrol is shown to attenuate typical senescence alterations on cell morphology, senescence-associated beta-galactosidase activity, and cell proliferation. The mechanisms implicated in this antisenescence effect seem to be independent of senescence-associated genes and proteins regulation but are reliant on cellular proteostasis improvement. In fact, resveratrol supplementation restores copper-induced increased protein content, attenuates BiP level, and reduces carbonylated and polyubiquitinated proteins by autophagy induction. Our data provide compelling evidence for the beneficial effects of resveratrol by mitigating CuSO4-SIPS stressful consequences by the modulation of protein quality control systems. These findings highlight the importance of a balanced cellular proteostasis and add further knowledge on molecular mechanisms mediating resveratrol antisenescence effects. Moreover, they contribute to identifying specific molecular targets whose modulation will prevent age-associated cell dysfunction and improve human healthspan. Liliana Matos, Alexandra Monteiro Gouveia, and Henrique Almeida Copyright © 2017 Liliana Matos et al. All rights reserved. Triethylenetetramine Synergizes with Pharmacologic Ascorbic Acid in Hydrogen Peroxide Mediated Selective Toxicity to Breast Cancer Cell Wed, 08 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/3481710/ Breast cancer is characterized by overexpression of superoxide dismutase (SOD) and downregulation of catalase and more resistance to hydrogen peroxide (H2O2) than normal cells. Thus, relatively high H2O2 promotes breast cancer cell growth and proliferation. However, excessive intracellular H2O2 leads to death of breast cancer cells. In cancer cells, high level ascorbic acid (Asc) is able to be autoxidized and thus provides an electron to oxygen to generate H2O2. In the present study, we demonstrated that triethylenetetramine (TETA) enhances Asc autoxidation and thus elevates H2O2 production in MCF-7 cells. Furthermore, Asc/TETA combination significantly impaired cancer cell viability, while having much milder effects on normal cells, indicating Asc/TETA could be a promising therapy for breast cancer. Moreover, SOD1 and N-acetyl-L-cysteine failed to improve MCF-7 cells viability in the presence of Asc/TETA, while catalase significantly inhibited the cytotoxicity of Asc/TETA to breast cancer cells, strongly suggesting that the selective cytotoxicity of Asc/TETA to cancer cells is H2O2-dependent. In addition, Asc/TETA induces RAS/ERK downregulation in breast cancer cells. Animal studies confirmed that Asc/TETA effectively suppressed tumor growth in vivo. In conclusion, TETA synergizes pharmacologic Asc autoxidation and H2O2 overproduction in breast cancer cells, which suppresses RAS/ERK pathway and results in apoptosis. Lianlian Wang, Xiaofang Luo, Cong Li, Yubing Huang, Ping Xu, Laetitia H. Lloyd-Davies, Thibaut Delplancke, Chuan Peng, Rufei Gao, Hongbo Qi, Chao Tong, and Philip Baker Copyright © 2017 Lianlian Wang et al. All rights reserved. Targeting Oxidative Stress for Treatment of Glaucoma and Optic Neuritis Wed, 08 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/2817252/ Glaucoma is a neurodegenerative disease of the eye and it is one of the leading causes of blindness. Glaucoma is characterized by progressive degeneration of retinal ganglion cells (RGCs) and their axons, namely, the optic nerve, usually associated with elevated intraocular pressure (IOP). Current glaucoma therapies target reduction of IOP, but since RGC death is the cause of irreversible vision loss, neuroprotection may be an effective strategy for glaucoma treatment. One of the risk factors for glaucoma is increased oxidative stress, and drugs with antioxidative properties including valproic acid and spermidine, as well as inhibition of apoptosis signal-regulating kinase 1, an enzyme that is involved in oxidative stress, have been reported to prevent glaucomatous retinal degeneration in mouse models of glaucoma. Optic neuritis is a demyelinating inflammation of the optic nerve that presents with visual impairment and it is commonly associated with multiple sclerosis, a chronic demyelinating disease of the central nervous system. Although steroids are commonly used for treatment of optic neuritis, reduction of oxidative stress by approaches such as gene therapy is effective in ameliorating optic nerve demyelination in preclinical studies. In this review, we discuss oxidative stress as a therapeutic target for glaucoma and optic neuritis. Atsuko Kimura, Kazuhiko Namekata, Xiaoli Guo, Takahiko Noro, Chikako Harada, and Takayuki Harada Copyright © 2017 Atsuko Kimura et al. All rights reserved. Bioenergetic Changes during Differentiation of Human Embryonic Stem Cells along the Hepatic Lineage Mon, 06 Feb 2017 12:10:08 +0000 http://www.hindawi.com/journals/omcl/2017/5080128/ Mitochondrial dysfunction has been demonstrated to result in premature aging due to its effects on stem cells. Nevertheless, a full understanding of the role of mitochondrial bioenergetics through differentiation is still lacking. Here we show the bioenergetics profile of human stem cells of embryonic origin differentiating along the hepatic lineage. Our study reveals especially the transition between hepatic specification and hepatic maturation as dependent on mitochondrial respiration and demonstrates that even though differentiating cells are primarily dependent on glycolysis until induction of hepatocyte maturation, oxidative phosphorylation is essential at all stages of differentiation. Branden M. Hopkinson, Claus Desler, Mark Kalisz, Peter Siig Vestentoft, Lene Juel Rasmussen, and Hanne Cathrine Bisgaard Copyright © 2017 Branden M. Hopkinson et al. All rights reserved. The Neuroprotective Effects of Brazilian Green Propolis on Neurodegenerative Damage in Human Neuronal SH-SY5Y Cells Mon, 06 Feb 2017 06:39:04 +0000 http://www.hindawi.com/journals/omcl/2017/7984327/ Oxidative stress and synapse dysfunction are the major neurodegenerative damage correlated to cognitive impairment in Alzheimer’s disease (AD). We have found that Brazilian green propolis (propolis) improves the cognitive functions of mild cognitive impairment patients living at high altitude; however, mechanism underlying the effects of propolis is unknown. In the present study, we investigated the effects of propolis on oxidative stress, expression of brain-derived neurotrophic factor (BDNF), and activity-regulated cytoskeleton-associated protein (Arc), the critical factors of synapse efficacy, using human neuroblastoma SH-SY5Y cells. Pretreatment with propolis significantly ameliorated the hydrogen peroxide- (H2O2-) induced cytotoxicity in SH-SY5Y cells. Furthermore, propolis significantly reduced the H2O2-generated reactive oxygen species (ROS) derived from mitochondria and 8-oxo-2′-deoxyguanosine (8-oxo-dG, the DNA oxidative damage marker) but significantly reversed the fibrillar β-amyloid and IL-1β-impaired BDNF-induced Arc expression in SH-SY5Y cells. Furthermore, propolis significantly upregulated BDNF mRNA expression in time- and dose-dependent manners. In addition, propolis induced Arc mRNA and protein expression via phosphoinositide-3 kinase (PI3K). These observations strongly suggest that propolis protects from the neurodegenerative damage in neurons through the properties of various antioxidants. The present study provides a potential molecular mechanism of Brazilian green propolis in prevention of cognitive impairment in AD as well as aging. Junjun Ni, Zhou Wu, Jie Meng, Aiqin Zhu, Xin Zhong, Shizheng Wu, and Hiroshi Nakanishi Copyright © 2017 Junjun Ni et al. All rights reserved. Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Diabetic Retinopathy Mon, 06 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/9702820/ Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and is the leading cause of blindness in young adults. Oxidative stress has been implicated as a critical cause of DR. Metabolic abnormalities induced by high-glucose levels are involved in the development of DR and appear to be influenced by oxidative stress. The imbalance between reactive oxygen species (ROS) production and the antioxidant defense system activates several oxidative stress-related mechanisms that promote the pathogenesis of DR. The damage caused by oxidative stress persists for a considerable time, even after the blood glucose concentration has returned to a normal level. Animal experiments have proved that the use of antioxidants is a beneficial therapeutic strategy for the treatment of DR, but more data are required from clinical trials. The aims of this review are to highlight the improvements to our understanding of the oxidative stress-related mechanisms underlying the development of DR and provide a summary of the main antioxidant therapy strategies used to treat the disease. Cheng Li, Xiao Miao, Fengsheng Li, Shudong Wang, Quan Liu, Yonggang Wang, and Jian Sun Copyright © 2017 Cheng Li et al. All rights reserved. Parental High-Fat Diet Promotes Inflammatory and Senescence-Related Changes in Prostate Sun, 05 Feb 2017 12:36:06 +0000 http://www.hindawi.com/journals/omcl/2017/4962950/ Background. Obesity and dietary habits are associated with increased incidences of aging-related prostatic diseases. The present study was aimed to investigate transgenerational effects of chronic high-fat diet (HFD) feeding on inflammation and senescence-related changes in prostate. Methods. Sprague-Dawley rats were kept on either normal or HFD one. Senescence-associated β-galactosidase (SA β-gal) activity, inflammation, and cellular proliferation were determined in the prostate. Results. Increased SA β-gal activity, expression of p53, and cell proliferation marker PCNA were observed in ventral prostate of HFD-fed rats. Immunostaining for p53 and PCNA revealed that the p53 immunopositive cells were primarily in stroma while PCNA immunopositive cells were epithelial cells. An increase in expression of cycloxygenase-2 (COX-2) and phosphorylation of nuclear factor-kappa B (NF-kB) was observed in prostate of weaning pups HFD-fed parents. However, in adult pups, irrespective of dietary habit, a significant increase in the expression of COX-2, PCNA, phosphorylation of NF-kB, infiltration of inflammatory cells, and SA β-gal activity was observed. Conclusions. Present investigation reports that HFD feeding promotes accumulation of p53 expressing cells, proliferation of epithelial cells, and senescence-related changes in prostate. Further, parental HFD-feeding upholds inflammatory, proliferative, and senescence-related changes in prostate of pups. Kulbhushan Tikoo, Ajit Vikram, Shweta Shrivastava, Gopabandhu Jena, Heta Shah, and Richa Chhabra Copyright © 2017 Kulbhushan Tikoo et al. All rights reserved. Amino Acid Catabolism in Alzheimer’s Disease Brain: Friend or Foe? Sun, 05 Feb 2017 11:07:13 +0000 http://www.hindawi.com/journals/omcl/2017/5472792/ There is a dire need to discover new targets for Alzheimer’s disease (AD) drug development. Decreased neuronal glucose metabolism that occurs in AD brain could play a central role in disease progression. Little is known about the compensatory neuronal changes that occur to attempt to maintain energy homeostasis. In this review using the PubMed literature database, we summarize evidence that amino acid oxidation can temporarily compensate for the decreased glucose metabolism, but eventually altered amino acid and amino acid catabolite levels likely lead to toxicities contributing to AD progression. Because amino acids are involved in so many cellular metabolic and signaling pathways, the effects of altered amino acid metabolism in AD brain are far-reaching. Possible pathological results from changes in the levels of several important amino acids are discussed. Urea cycle function may be induced in endothelial cells of AD patient brains, possibly to remove excess ammonia produced from increased amino acid catabolism. Studying AD from a metabolic perspective provides new insights into AD pathogenesis and may lead to the discovery of dietary metabolite supplements that can partially compensate for alterations of enzymatic function to delay AD or alleviate some of the suffering caused by the disease. Jeddidiah W. D. Griffin and Patrick C. Bradshaw Copyright © 2017 Jeddidiah W. D. Griffin and Patrick C. Bradshaw. All rights reserved. Identification of Patients Affected by Mitral Valve Prolapse with Severe Regurgitation: A Multivariable Regression Model Thu, 02 Feb 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/6838921/ Background. Mitral valve prolapse (MVP) is the most common cause of severe mitral regurgitation. Besides echocardiography, up to now there are no reliable biomarkers available for the identification of this pathology. We aim to generate a predictive model, based on circulating biomarkers, able to identify MVP patients with the highest accuracy. Methods. We analysed 43 patients who underwent mitral valve repair due to MVP and compared to 29 matched controls. We assessed the oxidative stress status measuring the oxidized and the reduced form of glutathione by liquid chromatography-tandem mass spectrometry method. Osteoprotegerin (OPG) plasma levels were measured by an enzyme-linked immunosorbent assay. The combination of these biochemical variables was used to implement several logistic regression models. Results. Oxidative stress levels and OPG concentrations were significantly higher in patients compared to control subjects ( versus and versus  pg/mL, respectively; ). The best regression model was able to correctly classify 62 samples out of 72 with accuracy in terms of area under the curve of 0.92. Conclusions. To the best of our knowledge, this is the first study to show a strong association between OPG and oxidative stress status in patients affected by MVP with severe regurgitation. Paola Songia, Benedetta Porro, Mattia Chiesa, Veronika Myasoedova, Francesco Alamanni, Elena Tremoli, and Paolo Poggio Copyright © 2017 Paola Songia et al. All rights reserved. Oxidative Stress in Infection and Consequent Disease Wed, 01 Feb 2017 14:04:49 +0000 http://www.hindawi.com/journals/omcl/2017/3496043/ Alexander V. Ivanov, Birke Bartosch, and Maria G. Isaguliants Copyright © 2017 Alexander V. Ivanov et al. All rights reserved. Oxidative Stress in the Newborn Tue, 31 Jan 2017 13:31:15 +0000 http://www.hindawi.com/journals/omcl/2017/1094247/ Giuseppe Buonocore, Serafina Perrone, and Maria Luisa Tataranno Copyright © 2017 Giuseppe Buonocore et al. All rights reserved. Alcoholic Extract of Eclipta alba Shows In Vitro Antioxidant and Anticancer Activity without Exhibiting Toxicological Effects Tue, 31 Jan 2017 11:28:44 +0000 http://www.hindawi.com/journals/omcl/2017/9094641/ As per WHO estimates, 80% of people around the world use medicinal plants for the cure and prevention of various diseases including cancer owing to their easy availability and cost effectiveness. Eclipta alba has long been used in Ayurveda to treat liver diseases, eye ailments, and hair related disorders. The promising medicinal value of E. alba prompted us to study the antioxidant, nontoxic, and anticancer potential of its alcoholic extract. In the current study, we evaluated the in vitro cytotoxic and antioxidant effect of the alcoholic extract of Eclipta alba (AEEA) in multiple cancer cell lines along with control. We have also evaluated its effect on different in vivo toxicity parameters. Here, we found that AEEA was found to be most active in most of the cancer cell lines but it significantly induced apoptosis in human breast cancer cell lines by disrupting mitochondrial membrane potential and DNA damage. Moreover, AEEA treatment inhibited migration in both MCF 7 and MDA-MB-231 cells in a dose dependent manner. Further, AEEA possesses robust in vitro antioxidant activity along with high total phenolic and flavonoid contents. In summary, our results indicate that Eclipta alba has enormous potential in complementary and alternative medicine for the treatment of cancer. Navneet Kumar Yadav, Rakesh Kumar Arya, Kapil Dev, Chetan Sharma, Zakir Hossain, Sanjeev Meena, K. R. Arya, J. R. Gayen, Dipak Datta, and R. K. Singh Copyright © 2017 Navneet Kumar Yadav et al. All rights reserved. Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K/Akt Signaling and Limits Ventilator-Induced Lung Injury Tue, 31 Jan 2017 08:50:20 +0000 http://www.hindawi.com/journals/omcl/2017/3715037/ The development of ventilator-induced lung injury (VILI) is still a major problem in mechanically ventilated patients. Low dose inhalation of hydrogen sulfide (H2S) during mechanical ventilation has been proven to prevent lung damage by limiting inflammatory responses in rodent models. However, the capacity of H2S to affect oxidative processes in VILI and its underlying molecular signaling pathways remains elusive. In the present study we show that ventilation with moderate tidal volumes of 12 ml/kg for 6 h led to an excessive formation of reactive oxygen species (ROS) in mice lungs which was prevented by supplemental inhalation of 80 parts per million of H2S. In addition, phosphorylation of the signaling protein Akt was induced by H2S. In contrast, inhibition of Akt by LY294002 during ventilation reestablished lung damage, neutrophil influx, and proinflammatory cytokine release despite the presence of H2S. Moreover, the ability of H2S to induce the antioxidant glutathione and to prevent ROS production was reversed in the presence of the Akt inhibitor. Here, we provide the first evidence that H2S-mediated Akt activation is a key step in protection against VILI, suggesting that Akt signaling limits not only inflammatory but also detrimental oxidative processes that promote the development of lung injury. Sashko Georgiev Spassov, Rosa Donus, Paul Mikael Ihle, Helen Engelstaedter, Alexander Hoetzel, and Simone Faller Copyright © 2017 Sashko Georgiev Spassov et al. All rights reserved. NRF2 as an Emerging Therapeutic Target Tue, 31 Jan 2017 06:00:35 +0000 http://www.hindawi.com/journals/omcl/2017/8165458/ Ian M. Copple, Albena T. Dinkova-Kostova, Thomas W. Kensler, Karen T. Liby, and W. Christian Wigley Copyright © 2017 Ian M. Copple et al. All rights reserved. African Ancestry Gradient Is Associated with Lower Systemic F2-Isoprostane Levels Tue, 31 Jan 2017 00:00:00 +0000 http://www.hindawi.com/journals/omcl/2017/8319176/ Context. Low levels of systemic F2-isoprostanes (F2-IsoP) increase the risk of diabetes and weight gain and were found in African Americans. Low F2-IsoPs could reflect an unfavorable metabolic characteristic, namely, slow mitochondrial metabolism in individuals with African ancestry. Objective. To examine differences in plasma F2-IsoPs in three groups with a priori different proportion of African ancestry: non-Hispanic Whites (NHWs), US-born African Americans (AAs), and West African immigrants (WAI). Design. Cross-sectional study. Setting. Georgia residents recruited from church communities. Participants. 218 males and females 25–74 years of age, who are self-identified as NHW (), AA (), or WAI (). Main Outcome Measure(s). Plasma F2-IsoPs quantified by gas chromatography-mass spectrometry. Results. After adjustment for age, gender, obesity, and other comorbidities, WAI had lower levels of plasma F2-IsoP than AA (beta-coefficient = −9.8, ) and AA had lower levels than NHW (beta-coefficient = −30.3, ). Similarly, among healthy nonobese participants, F2-IsoP levels were lowest among WAI, followed by AA, and the highest levels were among NHW. Conclusion. Plasma F2-IsoPs are inversely associated with African ancestry gradient. Additional studies are required to test whether optimization of systemic F2-IsoP levels can serve as means to improve race-specific lifestyle and pharmacological intervention targeted to obesity prevention and treatment. Francis Annor, Michael Goodman, Bharat Thyagarajan, Ike Okosun, Ayo Doumatey, Barbara A. Gower, and Dora Il’yasova Copyright © 2017 Francis Annor et al. All rights reserved. Oxidative Stress in Disease and Aging: Mechanisms and Therapies 2016 Thu, 26 Jan 2017 09:35:45 +0000 http://www.hindawi.com/journals/omcl/2017/4310469/ Claudio Cabello-Verrugio, Felipe Simon, Capucine Trollet, and Juan F. Santibañez Copyright © 2017 Claudio Cabello-Verrugio et al. All rights reserved. Decreased Tissue COX5B Expression and Mitochondrial Dysfunction during Sepsis-Induced Kidney Injury in Rats Thu, 26 Jan 2017 06:10:58 +0000 http://www.hindawi.com/journals/omcl/2017/8498510/ Background. Sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host response to infection. Sepsis is the dominant cause of acute kidney injury (AKI), accounting for nearly 50% of episodes of acute renal failure. Signaling cascades and pathways within the kidney are largely unknown and analysis of these molecular mechanisms may enhance knowledge on pathophysiology and possible therapeutic options. Material and Methods. 26 male Wistar rats were assigned to either a sham group (control, ) or sepsis group (; cecal ligature and puncture model, 24 and 48 hours after CLP). Surviving rats () were decapitated at 24 hours (early phase; ) or 48 hours (late phase; ) after CLP and kidneys removed for proteomic analysis. 2D-DIGE and DeCyder 2D software (-test, ) were used for analysis of significantly regulated protein spots. MALDI-TOF in combination with peptide mass fingerprinting (PMF) as well as Western Blot analysis was used for protein identification. Bioinformatic network analyses (STRING, GeneMania, and PCViz) were used to describe protein-protein interactions. Results. 12 spots were identified with significantly altered proteins () in the three analyzed groups. Two spots could not be identified. Four different proteins were found significantly changed among the groups: major urinary protein (MUP5), cytochrome c oxidase subunit B (COX5b), myosin-6 (MYH6), and myosin-7 (MYH7). A significant correlation with the proteins was found for mitochondrial energy production and electron transport. Conclusions. COX5B could be a promising biomarker candidate since a significant association was found during experimental sepsis in the present study. For future research, COX5B should be evaluated as a biomarker in both human urine and serum to identify sepsis. Jochen Hinkelbein, Lennert Böhm, Stefan Braunecker, Christoph Adler, Edoardo De Robertis, and Fabrizio Cirillo Copyright © 2017 Jochen Hinkelbein et al. All rights reserved.