Tums.ac.ir 1 Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Full list of author information is available at the end of the article?The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (/creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (/creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Mokhtari et al. DARU Journal of Pharmaceutical Sciences (2017) 25:Page 2 ofBackground Stroke is considered as one of the most leading cause of long-term disability and around the world [1]. Disruption of blood flow PubMed ID:/www.ncbi.nlm.nih.gov/pubmed/28607003 in the main brain blood supplying arteries such as middle cerebral artery (MCA) is an important reason for ischemic stroke by induction of hypoxia and glucose deprivation [2]. A complex series of biochemical and molecular mechanisms including excitotoxic glutamatergic signaling, outburst of reactive Beclabuvir site oxygen species (ROSs), over-production of inflammatory mediators induce the pathogenesis of cerebral ischemia by sudden death of a portion of neurons which leading wide range of neurological defects [3?]. It was shown that among brain neurons, pyramidal neurons of hippocampal CA1 region are sensitive to ischemia condition [6]. These neurons play critical roles in learning and memory functions. Passive avoidance memory impairment following brain ischemia is associated with degeneration of pyramidal neurons [7]. The lack of successful therapies leads to high mortality and poor prognosis of patients with brain ischemia [8]. Although, the early thrombolytic therapies were suggested to restoring the blood flow, reperfusion itself exacerbate injury in the infarct core, leading condition known as cerebral ischemia/reperfusion (I/R) injury [9, 10]. Up to now, therapeutic agents with different mechanism of anti-apoptosis [11, 12], antioxidant [13], antiinflammation [14] have been evaluated in animal models following the brain ischemia. Recent studies confirmed that thyroid hormones (THs) have broad neuroprotective effects on the nervous system [15]. THs (triiodothyronine [T3] and thyroxine [T4]) are essential for brain development and morphogenesis, as mental retardation can be observed in cases with congenital hypothyroidism [16, 17]. The anti-edema properties of THs in transient middle cerebral artery occlusion (tMCAo) model of ischemic brain have been confirmed [18]. T3 is less than T4 but more active form of THs than T4 [19]. Moreover, a specific transporter known as monocarboxylate 8 (MCT8) transfers T3 through blood brain barrier (BBB) [20]. The genomic actions of T3 are related to binding of this molecule to a specific receptor, known as thyroid hormone receptors (THRs). THRs are associated with the level of local expression of T3 and THRs by acting as hormone-inducible transcription factor [21]. The neuroprotective effects of non-genomic T3 are induced though activation of nitric oxide and vasodilation [22]. The neuroprotective benefits of THs established prior to its neurological insult. THs can control glutamate production, decrease oxidative stress and metabo.


E resolution mapping of oxi-mC and Lux analysis will provide insights into the effect of DNA modifications on DNA binding of transcriptional factors either genome-wide or at the loci-specific scale. In addition, understanding the role and importance of 5hmC and other further oxidized cytosine modifications in transcription will require temporal approaches for measuring active transcription, such as nascent-seq, and the capability of detecting temporal changes in methylation levels at high resolution. In conclusion, all of the aforementioned and many additional future research questions will benefit greatly from Lux’s unique features of accounting for sample-specific variation in experimental parameters when quantifying all cytosine modification levels from replicated BS-seq and oxi-mC-seq data sets. All of Lux’s functionality described above is implemented in the Lux software, which has been made freely available.Materials and methodsEmbryonic stem cell (310) 619-3046 culture and genomic DNA isolationmESCs (v6.5) were cultured in Knockout DMEM (Invitrogen) with 20 embryonic stem cell qualified fetal bovine serum (Germini Bio-product), 2 mM L-glutamine, 0.1 mM 2-mercaptoethanol, 0.1 mM nonessential amino acids, 50 units/ml penicillin/streptomycin and 1000 U/ml ESGRO (LIF; Chemicon). Tet2 was stably knocked down in v6.5 cells using electroporation with pSUPER-puro-Tet2shRNA (320V, 250F) followed by 1.5 g/ml puromycin selection for 7?0 days [60]. Genomic DNA was isolated with the DNeasy blood and tissue kit (Qiagen) by following the manufacturer’s instructions. Three independent cultures of wild-type and Tet2kd samples were used.Validation of Tet2 knockdown in mESCsTet2 knockdown efficiency was measured by quantitative PCR (qPCR) and western blot [49]. For qPCR, total RNA was isolated with an RNeasy kit (Qiagen, Chatsworth, CA, USA) and cDNA was made using SuperScript III reverse transcriptase (Invitrogen). qPCR was performed using FastStart Universal SYBR Green Master mix (Roche, Mannheim, Germany) on a StepOnePlus real-time PCR system (Applied Biosystems, Foster City, CA, USA). Gene expression was normalized to Gapdh. Primers used for qPCR are listed below: Tet1 forward: GAGCCTGTTCCTCGATGTGG Tet1 reverse: CAACCCACCTGAGGCTGTT Tet2 forward: AACCTGGCTACTGTCATTGCTCCA Tet2 reverse: ATGTTCTGCTGGTCTCTGTGGGAA Gapdh forward: GTGTTCCTACCCCCAATGTGT Gapdh reverse: ATTGTCATACCAGGAAATGAGCTT For western blot, nuclear proteins from parental and Tet2 knock-down mESCs were extracted as previously described [61]. Nuclear protein (30 g) was loaded on 4?2 Bis-Tris gels (Invitrogen) and transferred to nitrocellulose membrane. Tet2 was detected using antiTet2 (Abcam) antibodies. Loading control, beta-actin, was detected using anti-beta actin from Abcam.MiceWe used 4?-week-old female C57BL/6 mice obtained from Jackson labs for cell isolation. The mice were housed in a pathogen-free animal facility in the La Jolla Institute for Allergy and Immunology and were used according to protocols approved by the Institutional Animal Care and use Committee (IACUC).Preparation of thymocyte subsetsSubsets of thymocytes were isolated by cell sorting as previously described [54], after PubMed ID:/www.ncbi.nlm.nih.gov/pubmed/26866270 cell surface staining usingj?et al. Genome Biology (2016)7:Page 15 ofCD4 (GK1.5), CD8 (53?.7), CD3 (145-2C11), and CD24 (M1/69) (all from Biolegend). DP cells were CD4+ CD8 int/hi; CD4 SP cells were CD4CD3 hi, CD24 int/lo. Peripheral subsets were isolated after pooling spleen and lymph nodes. T cells were.


Ns caused by the presence of superoxide, hydrogen peroxide and hydroxyl radicals.Conclusion Combining all, we could conclude that the aqueous extract of Podophyllum hexandrum exhibits good antioxidant activity in both in vitro and in vivo experiments. In vitro antioxidant tests proved that the plant possesses components with strong superoxide and hydrogen peroxide radical scavenging activity. Study also suggests that the extract also possess potential to protect the kidney and lung tissue against oxidative damages and could be used as an effective protector against CCl 4 induced kidney and lung damages. Further works are needed to fully characterize the active principles present in the plant responsible for these functions and elucidate its possible mode of action.Co nt ro l C g Vi Cl rou ta 4 g p m 20 in rou m Eg p g 30 /kg rou m ex p g/ 50 kg trac m ex t g/ kg tra ex ct tra ct Co nt ro -l C g Vi Cl rou ta 4 g p m 20 in rou m Eg p g 30 /kg rou m ex p g/ 50 kg trac m ex t g/ kg tra ex ct tra ct –KidneyLungGanie et al. BMC Complementary and Alternative Medicine 2011, 11:17 /www.biomedcentral.com/1472-6882/11/Page 10 of12. Chawla R, Arora R, Singh S, Sagar RK, Sharma RK, Kumar R: Podophyllum hexandrum offers radioprotection by modulating free radical flux: role of aryl-tetralin lignans. eCAM 2006, 3:503-511. 13. Jung CHS, Choi IW, Park MW, Cho HY: Antioxidant properties of various solvent extracts from wild ginseng leaves. LWT PubMed ID:/www.ncbi.nlm.nih.gov/pubmed/28045099 2006, 39:266-274. 14. Ruch RJ, Cheng SJ, Klaunig JE: Carcinogenesis. 1989, 10:1003-1008. 15. Lowry OH, Rosenbrough NJ, Farr AI, Randall RJ: Protein estimation with the Folin phenol reagent. J Biol Chem 1951, 193:265-275. 16. Nichans WG, Samuelson D: Formation of malondialdehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 1968, 6:126-130. 17. Moren MA, Depierre JW, Mannervick B: Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochem Biophys Acta 1979, 582:67-78. 18. Sharma N, Trikha P, Athar M, Raisuddin S: Inhibition of benzo[a]pyreneand cyclophosphamide-induced mutagenicity by cinnamomum cassia. Mutat Res 2001, 480-481:179-188. 19. Haque R, Bin-Hafeez B, Parvez S, Pandey S, Sayeed I, Ali M, Raisuddin S: Aqueous extract of walnut (Juglans regia L.) protects mice against cyclophosphamide induced biochemical toxicity. Hum Exp Toxicol 2003, 22:473-480. 20. Beauchamp C, Fridovich I: Superoxide dismutase: Improved assays and an assay applicable to acrylamide gel. Anal Biochem 1971, 44:276-287. 21. Ko KM, Ip SP, Poon MK, Wu SS, Che CT, Ng KH, Kong YC: Effect of a ligninenriched fructus schisandrae extract on hepatic glutathione status in rats: protection against carbon tetrachloride toxicity. Planta Med 1995, 61:134-137. 22. Halliwell B, Gutteridge JMC, Cross CE: Free radicals, antioxidants and human disease: where are we now? Journal of Laboratory and Clinical Medicine 1992, 119:598-620. 23. Ames BN, Shigenaga MK, Hagen TM: Oxidants, antioxidants and the degenerative disease of aging. proceedings of the national academy of sciences of the United States of America 1993, 90:2894632180 7915-7922. 24. Prior RL: Fruits and vegetables in the prevention of cellular oxidative damage. American Journal of Clinical Nutrition 2003, 78:570s-578s. 25. Halliwell B, Gutteridge JMC: Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 1984, 219:44. 26. Minlotti G, Aust SD: The requirement of iron (III) in the initiation.

Edcentral.com/1471-2164/10/S3/SFigure 2 Protein functional association discovery. Comparison of the three distance metric capability in predicting

Edcentral.com/1471-2164/10/S3/SFigure 2 Protein functional association discovery. Comparison of the three distance metric capability in predicting interacting yeast protein pairs from genome-wide microarray expression data. The standard positive pairs are derived from the annotations of GO terms that got 5/6 votes of expert survey. (A) Results from Gasch et al. [11] data; (B) Results from Avara et al. [12] data. colon), measured on the Human Genome U95 Affymetrix microarray [20]. The last dataset consisted of diagnostic samples from diffuse large B-cell lymphoma patients, measured on the Human Genome U133A and U133B Affymetrix microarrays [21]. Among the 141 subtypes, 3 discrete subtypes had been identified: oxidative phosphorylation (49 samples), B-cell receptor/proliferation (50 samples), and host response (42 samples). Since it is possible that the datasets contained multiple signatures other than the known phenotypes, they had been preprocessed by applying a signal-to-noise ratio test and selecting the most up-regulated genes for each class [22], so that the observed phenotype would be the dominant signature in the data.Experiment and results For each of the described dataset, we calculated the distance matrix using the 5 approaches: Euclidean distance, Euclidean distance with z-score normalisation, Pearson correlation, Pearson correlation with z-score normalisation, and the newly proposed BayesGen. These distance matrices were then fed as inputs to the agglomerative hierarchical clustering to (817) 618-2714 obtain one linkage tree for each 3234240389 metric. We used average linkage, which defines the distance between two clusters as the average of all between-cluster distances. Formally, given2 clusters C1 and C2 of n1 and n2 objects respectively, the distance between C1 and C2 is:d(C1 , C 2 ) =1 n1nx1C1 , x 2 Cd( x1 , x 2 ).Hierarchical clustering does not require users to specify the number of clusters beforehand. One could later decides on the number of partitions by looking at the tree structure. However, this process is normally bias and based on one’s prior expectation about the data. In an attempt of achieving a reasonable fairness level for all approaches, we estimated the appropriate number of clusters for each tree using gap statistics [23]. The idea of gap statistics is to find the point at which the withincluster dispersion is minimised, by comparing it to a null reference distribution. More details about gap statistics is in the Method section. To evaluate the predicted clusters quality we used the adjusted Rand index [24] to compare between the known class labels and the cluster labels. The index ranges from 0 to 1, where 1 corresponds to perfect agreement, and 0 to the expected value of random cluster assignment. The computation detail of Rand index goes in the Method section. Table 1 presents the adjusted Rand indices obtained using different distance matrices as the input for the hierarchical clustering and gap statistics procedure. While the Bayesian generative input is the clear winnerPage 6 of(page number not for citation purposes)BMC Genomics 2009, 10(Suppl 3):S/www.biomedcentral.com/1471-2164/10/S3/STable 1: Clustering expression profiles into cancer subtypeseuclid General leukemia Pediatric leukemia Multiple tissues B-cell lymphoma Average 0.5447 0.1982 0.5304 0.0016 0.euclidNorm 0.1175 0.4789 0.9082 0.0008 0.corr 0.7491 0.2014 0.6416 0.4407 0.corrNorm 0.1817 0.9129 0.783 0.1745 0.bayesGen 0.8076 0.9413 0.9726 0.9053 0.Table 2:.

Mal alkaline phosphatase and bilirubin were suggestive of hepatocellular injury in absence of a cholestatic

Mal alkaline phosphatase and bilirubin were suggestive of hepatocellular injury in absence of a cholestatic etiology. With an effort to address the problem without having to discontinue AG-490 msds imatinib therapy, we decided to investigate in to the etiology of increased transaminases. Patient’s occasional alcohol intake history, normal viral hepatitis serologic studies, alpha fetoprotein level, ceruloplasmin level, magnetic resonance imaging of the abdomen were helpful in ruling out alcoholic liverdisease, viral hepatitis, focal nodular hyperplasia, malignant hepatic involvement, Budd-Chiari syndrome and Wilsons disease. Finally, on patient’s consent, a liver biopsy with iron stain revealed prominent iron deposition within hepatic parenchymal cells and portal areas as well as mild portal fibrosis (Figure 2). Consistently, the ferritin levels were found to be markedly elevated, while transferrin saturation levels were within normal limits (Figure 1). These findings prompted the genetic analysis for hereditary hemochromatosis (C282Y and H63D loci), which turned out to be negative. Following discussion with patient, phlebotomy was initiated which dramatically brought the liver enzymes back to normal levels (Figure 1). Following the first phlebotomy, the imatinib dosage was increased to 600 mg daily and continued thereafter. Patient had the initial two phlebotomies 3 months apart followed by every 6 months. Patient’s liver functions remained within normal limits until his recent follow up at 42 months after initiating imatinib therapy and roughly 15 months following initiation of phlebotomy. Hence the patient was able to maintain imatinib treatment with continued molecular remission, taking recourse only to periodic phlebotomy at 3-6 month intervals. Patient tolerated phlebotomy well with no side effects or anemia.Figure 1. Imatinib causes elevated liver transaminases. Temporal relationship of imatinib therapy with markedly elevated ALT and AST levels secondary to hepatic hemosiderosis. The concurrently elevated serum ferritin level and the time of initiation of treatment with phlebotomy are indicated. Patient was on imatinib 400-600 mg daily during the whole period of time except a brief discontinuation of 2 weeks in the second month due to neutropenic fever. The dosage of imatinib is indicated. The break in the line indicates the 2-week period during which imatinib was discontinued for neutropenic fever.Page 2 of(page number not for citation purposes)Cases Journal 2009, 2:/casesjournal.com/casesjournal/article/view/Figure 2. Hepatic hemosiderosis is (707) 265-7954 a likely consequence of imatinib treatment. Liver biopsy with iron stain revealing prominent iron deposition within hepatic parenchymal cells and portal areas (indicated).DiscussionThe discovery of the BCR-Abl translocation in CML culminated in the realization of the dream of targeted therapy in cancer by the small molecule tyrosine kinase inhibitor imatinib [9]. The recently reported result of 6-year Phase III clinical trial confirms the durability of response to imatinib in addition to the declining incidence of adverse events over time [1]. Currently, indications of imatinib include the treatment of CML and gastrointestinal stromal tumor (GIST). Most patients with newly diagnosed chronic phase CML experience complete cytogenetic responses with imatinib treatment, however continuation of treatment is required to prevent molecular or cytogenetic relapse [8]. According to the literature, recurren.

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D space after the onset of experimental SAH was able to inhibit vasospasm. Thus, in the clinical setting, we suggest that cisternal irrigation fluid is the optimal route of trehalose administration, and is anticipated to have an additional or synergistic therapeutic effect on complications of SAH when combined with existing therapeutic modalities.Study limitationsThere are some limitations in this study. First, while we showed suppressive effects of trehalose on inflammation, oxidative stress, and vasospasm, we could not fully elucidate the relationship between these pathological mechanismsAuthors’ contributions RE participated in the design of the study, performed in vivo experiments using rabbits and rats, and drafted the manuscript. NS participated in theEchigo et al. Journal of Translational Medicine 2012, 10:80 /www.translational-medicine.com/content/10/1/Page 12 ofdesign of the study, performed in vitro experiments, and drafted the manuscript. KK partly performed in vivo experiments using rabbits. FY performed immunohistological experiments. YK-K partly performed in vivo experiments using rats. TO performed in vitro PLA2 assay. AF, YK, MN, SS, MM, TS, UC, and NS participated in the study design and coordination and drafted the manuscript. All authors read and approved the final manuscript. Received: 15 December 2011 Accepted: 30 April 2012 Published: 30 April 2012 References 1. van Gijn J, Kerr RS, Rinkel GJ: Subarachnoid haemorrhage. Lancet 2007, 369:306?18. 2. Macdonald RL, Kassell NF, Mayer S, Ruefenacht D, Schmiedek P, Weidauer S, Frey A, Roux S, Pasqualin A, Investigators C: Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (get BQ-123 CONSCIOUS-1) randomized, double-blind, placebocontrolled phase 2 dose-finding trial. Stroke 2008, 39:3015?021. 3. Macdonald RL, Pluta RM, Zhang JH: Cerebral vasospasm after subarachnoid hemorrhage: the emerging revolution. Nat Clin Pract Neurol 2007, 3:256?63. 4. Sercombe R, Dinh YR, Gomis P: Cerebrovascular inflammation following subarachnoid hemorrhage. Jpn J Pharmacol 2002, 88:227?49. 5. Zhou M-L, Shi J-X, Hang C-H, Cheng H-L, Qi X-P, Mao L, Chen K-F, Yin H-X: Potential contribution of nuclear factor-B to cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits. J Cereb Blood Flow Metab 2007, 27:1583?592. 6. Rodriguez y Baena R, Gaetani P, Folco G, Vigano T, Paoletti P: Arachidonate metabolites and vasospasm after subarachnoid haemorrhage. Neurol Res 1986, 8:25?2. 7. Ayer RE, Zhang JH: Oxidative stress in subarachnoid haemorrhage: significance in acute brain injury and vasospasm. Acta Neurochir Suppl 2008, 104:33?1. 8. Endo H, Nito C, Kamada H, Yu F, Chan PH: Reduction in oxidative stress by superoxide dismutase overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt/glycogen synthase kinase-3 survival signaling. J Cereb Blood Flow Metab 2007, 27:975?82. 9. Komotar RJ, Zacharia BE, Valhora R, Mocco J, Connolly ES Jr: Advances in vasospasm treatment and prevention. J Neurol Sci 2007, 261:134?42. 10. Al-Tamimi YZ, Orsi NM, Quinn AC, Homer-Vanniasinkam S, Ross SA: A review of delayed ischemic neurologic deficit following aneurysmal subarachnoid hemorrhage: historical overview, current treatment, and pathophysiology. World Neurosurg 2676177840 2010, 73:654?67. 11. Elbein AD, Pan YT, Pastuszak I, Carroll D: New insights on trehalose: a multifunctional molecule. Glycobiology 2003, 13:17R?7R. 12. Jain NK, Ro.


Ocessed, high-sugar, and low-nutrient foods began. Recent advances in the field of nutritional psychiatry have made it clear that there are indeed remarkable ways in which nutrition influences brain structure and function, as well as mental health and cognition [11,17]. Even shortterm adoption of traditional dietary patterns can beneficially influence mood and cognition [18]. An increasing number of epidemiological studies, including several that have followed subjects over time, have linked adherence to traditional dietary patterns with lowered risk of depressive symptoms, anxiety, and maintenance of academic progress [19-25]. Meat consumption, often painted with the same brush (without considering processing) and vilified without scientific justification [26,27], has been associated with lower risk of depression [28,29], and meat abstinence has been linked with higher risk of mental health disorder [30]. This is not to suggest that meat is a mental health panacea; a strict plant-based diet, lower in sweets and rich in fruits and vegetables, may also support positive mental health [31]. Connections between nutrition and mental health extend to mortality. For example, those with a lifetime history of attempted suicide have been reported to consume significantly less meat, fruits, and vegetables [32]. On the other hand, healthy dietary patterns characterized by higher intake of vegetables, fruits, potatoes, soy products, mushrooms, seaweed, and fish are associated with a decreased risk of suicide [33]. The developmental origins of health and disease (DOHaD) construct provides clear evidence that early life is a critical time in subsequent risk of non-communicable diseases [34,35]. With his groundbreaking studies on the long-lasting effects of environmental variables experienced in early life, Dubos helped to place DOHaD under the scientific microscope [36]. Today, pre- and post-natal nutrition is now being clearly linked to later mental health outcomes and childhood nutrition with academic performance [37-39]. Specific components of traditional dietary patterns, including, but not limited to cocoa polyphenols, green tea, coffee, grapes, and various spices, have also been linked to positive mood, cognitive efficiency, and a decreased risk of depressive symptoms [40-46]. Experimental research shows that the phytochemicals found within traditional foods (e.g., tea polyphenols and (507) 329-4669 resveratrol) and omega-3 fats that are relatively more abundant in fish and free-range meats can influence brain function via neurotransmitter availability for synaptic communicationLogan et al. Journal of Physiological Anthropology (2015) 34:Page 3 of[47-49]. They can also increase the production of neurotrophic factors responsible for neuronal structure and function [50-52]. The evolutionary advantage of phytochemicals to both plants (505) 910-4963 and humans has been postulated [53]. When humans encounter psychological stress, they often turn to calorie-dense, nutritionally poor “comfort foods” [54-56]. In otherwise healthy adults, wherein negative mood state is experimentally induced by researchers, the direct infusion of fatty acids in the stomach (therefore bypassing olfactory, visual, and gustatory cues) can quickly rectify the lowered mood state [57]. As much as phytochemicals may protect us, are there evolutionary factors that might lead modern humans away from traditional dietary practices? Does fast food create a dependence? It would make sense that in our Paleolithic.

Endrocytes isolated from adult brain. Brain 2002, 125:2469-2480. Sundaresan M, Yu ZX, Ferrans VJ, Irani

Endrocytes isolated from adult brain. Brain 2002, 125:2469-2480. Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T: Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 1995, 270:296-299. Algeciras-Schimnich A, Pietras EM, Barnhart BC, Legembre P, Vijayan S, Ornipressin dose Holbeck SL, Peter ME: Two CD95 tumor classes with different sensitivities to antitumor drugs. Proc Natl Acad Sci USA 2003, 100:11445-11450. Samuels Y, Diaz LA Jr, Schmidt-Kittler O, Cummins JM, Delong L, Cheong I, Rago C, Huso DL, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE: Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 2005, 7:561-573.Tang et al. BMC Biology 2011, 9:18 /www.biomedcentral.com/1741-7007/9/Page 16 of33. Johnstone RW, Frew AJ, Smyth MJ: The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer 2008, 8:782-798. 34. Perez-Cruz I, Carcamo JM, Golde DW: Vitamin C inhibits FAS-induced apoptosis in monocytes and U937 cells. Blood 2003, 102:336-343. 35. Mantovani G, Maccio A, Madeddu C, Mura L, Gramignano G, Lusso MR, Massa E, Mocci M, Serpe R: Antioxidant agents are effective in inducing lymphocyte progression through cell cycle in advanced cancer patients: assessment of the most important laboratory indexes of cachexia and oxidative stress. J Mol Med 2003, 81:664-673. 36. Perez-Cruz I, Carcamo JM, Golde DW: Caspase-8 dependent TRAIL-induced apoptosis in cancer cell lines is inhibited by vitamin C and catalase. Apoptosis 2007, 12:225-234. 37. Geserick P, Drewniok C, Hupe M, Haas TL, Diessenbacher P, Sprick MR, Schon MP, Henkler F, Gollnick H, Walczak H, Leverkus M: Suppression of cFLIP is sufficient to sensitize human melanoma cells to TRAIL- and CD95L-mediated apoptosis. Oncogene 2008, 27:3211-3220. 38. McGahon A, Bissonnette R, Schmitt M, Cotter KM, Green DR, PubMed ID:/www.ncbi.nlm.nih.gov/pubmed/26266977 Cotter TG: BCR-ABL maintains resistance of chronic myelogenous leukemia cells to apoptotic cell death. Blood 1994, 83:1179-1187. 39. Cheng J, Hylander BL, Baer MR, Chen X, Repasky EA: Multiple mechanisms underlie resistance of leukemia cells to Apo2 ligand/TRAIL. Mol Cancer Ther 2006, 5:1844-1853. 40. Mohr A, B eker C, Gough RP, Zwacka RM: MnSOD protects colorectal cancer cells from TRAIL-induced apoptosis by inhibition of Smac/DIABLO release. Oncogene 2008, 27:763-774. 41. Hietakangas V, Poukkula M, Heiskanen KM, Karvinen JT, Sistonen L, Eriksson JE: Erythroid differentiation sensitizes K562 leukemia cells to TRAIL-induced apoptosis by downregulation of c-FLIP. Mol Cell Biol 2003, 23:1278-1291. 42. Klas C, Debatin KM, Jonker RR, Krammer PH: Activation interferes with the APO-1 pathway in mature human T cells. Int Immunol 1993, 5:625-630. 43. Harper N, MacFarlane M: Recombinant TRAIL and TRAIL receptor analysis. Methods Enzymol 2008, 446:293-313. 44. Andrieu N, Salvayre R, Jaffr ou JP, Levade T: Low temperatures and hypertonicity do not block cytokine-induced stimulation of the sphingomyelin pathway but inhibit nuclear factor-B activation. J Biol Chem 1995, 270:24518-24524.doi:10.1186/1741-7007-9-18 Cite this article as: Tang et al.: The scavenging of superoxide radicals promotes apoptosis induced by a novel cell-permeable fusion protein, sTRAIL:FeSOD, in tumor necrosis factor-related apoptosis-inducing ligand-resistant leukemia cells. BMC Biology 2011 9:18.Submit your next manuscript to BioMed Central and take full advantage of:?Convenient online submission ?Thorough peer review ?No space const.

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S, including anxiety and sleep disorders, epilepsy and seizures, learning and memory disorders [24-27]. Since GABA is abundant in short-term fermented Pu-erh tea [7] and has a strong antioxidant activity [28], it might protect human cells from injury by scavenging of free radicals. Therefore, the aim of this study was to investigate the protective mechanisms of GABA and Pu-erh tea leaf extract on KA-induced injury in neuronal cells in vivo and in vitro.was comprised of methanol and H2O (62:38), the flow speed was 1.0 mL/min, the detection wavelength was 330 nm, and the injection amount was 20 L. GABA standard liquor was prepared by diluting GABA with pure water to different strengths (10, 50, 100, 150, and 200 g/mL) to obtain different chroma values. The derivatization reaction was observed with GABA liquor at five values of chroma. Each sample was tested three times, and the average value of the absorbance at different values of concentration was calculated.Oxidative stress in miceMethodsMaterialsGABA and kainic acid (KA) were obtained from SigmaAldrich (Steinem, Germany) and Cayman Chemical (Ann Arbor, MI, USA), 2′, 7′-dichlorodihydrofluorescein diacetate (H 2 DCF-DA) was obtained from Molecular Probes (3305174225 Eugene, OR, USA).Pu-Erh tea leaf extractPu-Erh tea leaves were prepared as described by Hou et al [8]. Briefly, Pu-Erh tea leaves were ground to a fine powder with the aid of a stainless-steel mill and stored and dried to constant weight in a vacuum desiccator. With regard PubMed ID:/www.ncbi.nlm.nih.gov/pubmed/26080418 to the extraction procedure, triplicate onegram samples of Pu-Erh powder from each site was mixed with 20 ml of reverse osmosis water, vortexed vigorously for 5 min, and then centrifuged at 2,000 ?g for 10 min. The tea extracts were sterilized by filtration through a 0.25 m Millipore membrane filter (Millipore, Bedford, USA).Determination of GABA contentThe quantity of GABA in extracts of Pu-Erh tea was determined using the method described by Zhang and Bown [29]. Tea liquor was prepared as described above with 200 mg of dry tea powder. Samples of standard tea liquor (1 mL each) were placed in glass tubes to which was added 0.6 mL of 0.1 M lysis buffer and 1 mL of 0.3 2-hydroxynaphthaldehyde (the derivatizing reagent) (TCI, Japan). The tubes were placed in a water bath for 10 min maintained at 80 and then cooled to room temperature. Sufficient methanol was then added to give a final volume of 5 mL. The guard and analytical column used in HPLC analysis was Merck LiChrosper100 RP18 (5 m, 4.0 mm i.d. ?15 cm). The mobile phaseAdult male FVB mice, body weight 30-35 g, were used for this experiment. SE was induced by KA (10 mg/ml in phosphate-buffered saline (PBS), 10 mg/kg, subcutaneous injection). Pu-Erh tea leaf (PETL) powder and GABA was separately diluted in normal saline 10 mg/ml and 1 mg/ ml. The animals were fed with PETL (10 mg/kg) and GABA by gavage for 3 days before the KA experiment. The control group was fed with an equal volume of vehicle (normal saline). The procedures were conducted in accordance with the Taichung Veterans General Hospital Animal Care and Use Committee, Taichung, Taiwan (IACUC Approval No. LA-99741) and all possible steps were taken to avoid animals’ suffering at each stage of the experiment. Diazepam at lethal dosage, 60 mg/kg i.p., was given to stop seizures 2 h after KA injection and the animals were sacrificed by decapitation under CO 2 asphyxia. The whole brain was immediately removed and frozen in liquid nitrogen and stored at -.

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Most resistant and/ or fastest growing cells. This is due to the fact that usually slowly growing tumor cells and sensitive subpopulations die out after commencement of therapy, and therefore it is sufficient to design the therapy to target the fast growing tumor cells and resistant population. As an example see the mathematical model developed by [54] to model the number of proliferating as well as non-proliferating normal cells as a 9166469110 function of time post treatment when incorporating the selection of the fastest growing subpopulation to capture the tissue damage at the conclusion of therapy and of the subsequent healing kinetics. Hlatky et al. [60] studied the variable response of tumor cells to therapeutic treatment in ionizing radiation by modeling the resensitization process; whichBadri and Leder Biology Direct (2016) 11:Page 4 ofFig. 1 Relationship between TCP and number of 2.0 Gy fractions for different tumor population variabilities based on the model developed by Zagras et al. [101]. The fraction of surviving cells is assumed to be normally distributed. The standard deviation of the normal distribution measures the homogeneity of tumor cellsincludes redistribution and reoxygenation. The resensitization process states that after the dose is delivered, a large fraction of damage occurs among the radiosensitive cells, resulting in decreased average radiosensitivity. However these changes are reversible; and the remaining subpopulation are driven into more radiosensitive states as time passes [14, 60]. Considering a smooth function for absolute number of cell that have sensitivity at time t, i.e. n(, t), we can write the equation explaining the fluctuating diversity of a population with fixed size using a Kolmogorov forward equation as (see [60] for more details) : n? t ?1 2 ?- D- u n t 2 n ?0 ? 2 �k:1 2 N ?N ??exp -0 D ? G T ?G ?D2??where N(t) shows the total population at time t, D is total radiation dose delivered for period (0,T), and G is the Lea-Catcheside function [60]. Equation (2) can be considered as the elementary LQ model with being replaced by its average 0, and being replaced by its modified value. Results of their analysis support the hypothesis that the therapeutic paradigm of low dose rate or fractionated radiation can help conquer radioresistance in hypoxic tumors [91, 97]. This is due to the fact that a large fractionation interval (parameter T in (2)) allows the tumor population to complete the reoxygenation process and thereby the tumor population radioresistance due to oxygenation status will be minimized. This phenomenon is supported by a smaller coefficient for D2 in Eq. (2). One year later, Brenner et al. developed a parsimonious model to include the resensitization effect into the LQ model. In the extended model, designated LQR, survival is written as a function of dose d as 1 2 2 exp -d- – d ??2 where the term 1 2 d 2 refers PubMed ID:/www.ncbi.nlm.nih.gov/pubmed/28461567 to cellular diversity, and is 2 given by the uncertainty about the cell kill by one-track action of radiation, i.e. parameter [14]. The cell survival values based on Brenner et al. model (Eq. (3)) are plotted in Fig. 2 for values of 2 = 0, 0.01 and 0.09 for cell population without, low and high diversity,??where D is the dose rate, u denotes the average number of DSB per cell, 1 u2 shows the average rate at which 2 binary misreapirs removes DSB by lethal rearrangements, k displays the rate at which cells change their radiation sensitivity, and 0 and 2 represent the.