Publications

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enhanced cellular uptake of antisecretory peptide af-16 through proteoglycan binding.peptide af-16, which includes the active site of antisecretory factor protein, has antisecretory and anti-inflammatory properties, making it a potent drug candidate for treatment of secretory and inflammatory diseases such as diarrhea, inflammatory bowel diseases, and intracranial hypertension. despite remarkable physiological effects and great pharmaceutical need for drug discovery, very little is yet understood about af-16 mechanism of action. in order to address interaction mechanisms, we inv ...201425289567
the tarantula toxin jingzhaotoxin-xi (κ-theraphotoxin-cj1a) regulates the activation and inactivation of the voltage-gated sodium channel nav1.5.specific peptide toxins interact with voltage-gated sodium channels by regulating the activation or inactivation of targeted channels. however, few toxins possessing dual effects have been identified. in the present study, we showed that jingzhaotoxin-xi/κ-theraphotoxin-cj1a (jztx-xi), a 34-residue peptide from the venom of the chinese spider chilobrachys jingzhao, inhibits the sodium conductance (ic50 = 124 ± 26 nm) and slows the fast inactivation (ec50 = 1.18 ± 0.2 μm) of nav1.5 expressed in c ...201425240294
triphlorethol-a from ecklonia cava up-regulates the oxidant sensitive 8-oxoguanine dna glycosylase 1.this study investigated the protective mechanisms of triphlorethol-a, isolated from ecklonia cava, against oxidative stress-induced dna base damage, especially 8-oxoguanine (8-oxog), in chinese hamster lung fibroblast v79-4 cells. 8-oxoguanine dna glycosylase-1 (ogg1) plays an important role in the removal of 8-oxog during the cellular response to dna base damage. triphlorethol-a significantly decreased the levels of 8-oxog induced by h2o2, and this correlated with increases in ogg1 mrna and ogg ...201425353254
a high affinity recombinant antibody to the human epha3 receptor with enhanced adcc activity.epha3 is expressed in solid tumors and leukemias and is an attractive target for the therapy. we have generated a panel of humaneered® antibodies to the ligand-binding domain using a fab epitope-focused library that has the same specificity as monoclonal antibody miiia4. a high-affinity antibody was selected that competes with the miiia4 antibody for binding to epha3 and has an improved affinity of ∼1 nm. in order to generate an antibody with potent cell-killing activity the variable regions wer ...201425413948
protective effects of kojic acid on the periphery blood and survival of beagle dogs after exposure to a lethal dose of gamma radiation.in previous studies, it has been shown that pretreatment with kojic acid (ka) not only increased the 30 day survival rate of mice after exposed to a lethal dose of gamma radiation but also had significant radioprotective effects on the hematopoietic system, the immune system and dna of mice exposed to a 4 gy sublethal dose of radiation. furthermore, pretreatment with ka has also been shown to protect chinese hamster ovary (cho) cells against ionizing radiation-induced damage. in this investigati ...201425409121
moonlighting proteins in sperm-egg interactions.sperm-egg interaction is a highly species-specific step during the fertilization process. the first steps consist of recognition between proteins on the sperm head and zona pellucida (zp) glycoproteins, the acellular coat that protects the oocyte. we aimed to determine which sperm head proteins interact with zp2, zp3 and zp4 in humans. two approaches were combined to identify these proteins: immunoblotting human spermatozoa targeted by antisperm antibodies (asas) from infertile men and far-weste ...201425399599
a pan-cancer analysis of alternative splicing events reveals novel tumor-associated splice variants of matriptase.high-throughput transcriptome sequencing allows identification of cancer-related changes that occur at the stages of transcription, pre-messenger rna (mrna), and splicing. in the current study, we devised a pipeline to predict novel alternative splicing (as) variants from high-throughput transcriptome sequencing data and applied it to large sets of tumor transcriptomes from the cancer genome atlas (tcga). we identified two novel tumor-associated splice variants of matriptase, a known cancer-asso ...201425506199
enhanced susceptibility of ovaries from obese mice to 7,12-dimethylbenz[a]anthracene-induced dna damage.7,12-dimethylbenz[a]anthracene (dmba) depletes ovarian follicles and induces dna damage in extra-ovarian tissues, thus, we investigated ovarian dmba-induced dna damage. additionally, since obesity is associated with increased offspring birth defect incidence, we hypothesized that a dmba-induced dna damage response (ddr) is compromised in ovaries from obese females. wild type (lean) non agouti (a/a) and kk.cg-ay/j heterozygote (obese) mice were dosed with sesame oil or dmba (1mg/kg; intraperitone ...201425448685
cyto-genotoxicity assessment of potential radioprotector, 3,3'-diselenodipropionic acid (dsepa) in chinese hamster ovary (cho) cells and human peripheral blood lymphocytes.our previous study showed that 3,3'-diselenodipropionic acid (dsepa), a simple, stable, and water-soluble organoselenium exhibiting glutathione peroxidase (gpx)-like activity offered good radioprotection under in vitro and in vivo conditions. herein, we investigated the anti-genotoxic effect of dsepa in model cellular systems such as chinese hamster ovary (cho) cell line and human peripheral lymphocytes after exposure to γ-radiation. the measurements on the induction of γ-h2ax foci and micronucl ...201425440905
dimer-dependent intrinsic/basal activity of the class b g protein-coupled receptor pac1 promotes cellular anti-apoptotic activity through wnt/β-catenin pathways that are associated with dimer endocytosis.the high expression of pacap (pituitary adenylate cyclase-activating polypeptide)-preferring receptor pac1 is associated with nerve injury and tumors. our previous report (yu r, et al. plos one 2012; 7: e51811) confirmed the dimerization of pac1 and found that the m-pac1 mutation in the n-terminal first cys/ala lost the ability to form dimers. in this study, chinese hamster ovary (cho-k1) cells overexpressing wild-type pac1 (pac1-cho) had significantly higher anti-apoptotic activities against se ...201425426938
functional bioassays for immune monitoring of high-risk neuroblastoma patients treated with ch14.18/cho anti-gd2 antibody.effective treatment of high-risk neuroblastoma (nb) remains a major challenge in pediatric oncology. human/mouse chimeric monoclonal anti-gd2 antibody (mab) ch14.18 is emerging as a treatment option to improve outcome. after establishing a production process in chinese hamster ovary (cho) cells, ch14.18/cho was made available in europe for clinical trials. here, we describe validated functional bioassays for the purpose of immune monitoring of these trials and demonstrate gd2-specific immune eff ...201425226154
dimerisation of the drosophila odorant coreceptor orco.odorant receptors (ors) detect volatile molecules and transform this external information into an intracellular signal. insect ors are heteromers composed of two seven transmembrane proteins, an odor-specific orx and a coreceptor (orco) protein. these ors form ligand gated cation channels that conduct also calcium. the sensitivity of the ors is regulated by intracellular signaling cascades. heterologously expressed orco proteins form also non-selective cation channels that cannot be activated by ...201425221476
development and qualification of a high sensitivity, high throughput q-pcr assay for quantitation of residual host cell dna in purification process intermediate and drug substance samples.methods of high sensitivity, accuracy and throughput are needed for quantitation of low level residual host cell dna in purification process intermediates and drug substances of therapeutic proteins. in this study, we designed primer/probe sets targeting repetitive alu repeats or alu-equivalent sequences in the human, chinese hamster and murine genomes. when used in quantitative polymerase chain reactions (q-pcrs), these primer/probe sets showed high species specificity and gave significantly hi ...201425165010
accurate comparison of antibody expression levels by reproducible transgene targeting in engineered recombination-competent cho cells.over the years, chinese hamster ovary (cho) cells have emerged as the major host for expressing biotherapeutic proteins. traditional methods to generate high-producer cell lines rely on random integration(s) of the gene of interest but have thereby left the identification of bottlenecks as a challenging task. for comparison of different producer cell lines derived from various transfections, a system that provides control over transgene expression behavior is highly needed. this motivated us to ...201425158835
methylene blue modulates β-secretase, reverses cerebral amyloidosis, and improves cognition in transgenic mice.amyloid precursor protein (app) proteolysis is required for production of amyloid-β (aβ) peptides that comprise β-amyloid plaques in the brains of patients with alzheimer disease (ad). here, we tested whether the experimental agent methylene blue (mb), used for treatment of methemoglobinemia, might improve ad-like pathology and behavioral deficits. we orally administered mb to the aged transgenic psapp mouse model of cerebral amyloidosis and evaluated cognitive function and cerebral amyloid path ...201425157105
toxicity of drinking water disinfection byproducts: cell cycle alterations induced by the monohaloacetonitriles.haloacetonitriles (hans) are a chemical class of drinking water disinfection byproducts (dbps) that form from reactions between disinfectants and nitrogen-containing precursors, the latter more prevalent in water sources impacted by algae bloom and municipal wastewater effluent discharge. hans, previously demonstrated to be genotoxic, were investigated for their effects on the mammalian cell cycle. treating chinese hamster ovary (cho) cells with monohans followed by the release from the chemical ...201425185076
site-2 protease responds to oxidative stress and regulates oxidative injury in mammalian cells.site-2 protease (s2p) is a membrane-embedded protease that site-specifically cleaves intramembrane transcription factors, a necessary step for their maturation. s2p is well known to regulate cholesterol biosynthesis and endoplasmic reticulum stress in mammalian cells. in this study, we hypothesized that s2p could be responsible for the regulation of cellular oxidative injury under oxidative stress. wild type chinese hamster ovary (wt cho) cells and their mutant m19 cells with defective s2p gene ...201425183265
biologically active constituents from salix viminalis bio-oil and their protective activity against hydrogen peroxide-induced oxidative stress in chinese hamster ovary cells.the protective antioxidative effect of the phenolic extract (pe) isolated from salix viminalis pyrolysis derived bio-oil was shown in vitro on the chinese hamster ovary (cho) cells exposed to hydrogen peroxide (h2o2). cells pretreated with 0.05 μg/ml pe after exposure to different concentrations of h2o2 (300-900 μm) showed up to 25 % higher viability than the unpretreated ones. the antioxidative effect of pe was also observed in a time-dependent manner. the results were confirmed by visual exami ...201425172057
in vitro evaluation of cordyceps militaris as a potential radioprotective agent.radiation is an important component of therapy for a wide range of malignant conditions. however, it triggers dna damage and cell death in normal cells and results in adverse side-effects. cordyceps militaris (c. militaris), a traditional medicinal mushroom, produces the bioactive compound, cordycepin (3'-deoxyadenosine) and has multiple pharmacological activities, such as antitumor, antimetastatic, antioxidant and immunomodulatory effects. the present study was undertaken to investigate whether ...201425176413
effect of lithium chloride on the production and sialylation of fc-fusion protein in chinese hamster ovary cell culture.lithium chloride (licl), which is a specific inhibitor of glycogen synthase kinase-3β, is known to induce cell cycle arrest at the g2/m phase and to regulate apoptosis. to determine the potential of licl as a chemical additive to enhance specific productivity (q p) of recombinant chinese hamster ovary (rcho) cells through cell cycle arrest at g2/m phase, rcho cells producing fc-fusion protein were cultivated in serum-free media with licl concentrations ranging from 0 to 20 mm. the addition of li ...201425132065
reduction in c-terminal amidated species of recombinant monoclonal antibodies by genetic modification of cho cells.during development of recombinant monoclonal antibodies in chinese hamster ovary (cho) cells, c-terminal amidated species are observed. c-terminal amidation is catalysed by peptidylglycine α-amidating monooxygenase (pam), an enzyme known to be expressed in cho cells. the significant variations between clones during clone selection, and the relatively high content of amidated species (up to 15%) in comparison to reference material (4%), led us to develop a cell line with reduced production of c-t ...201425123359
high-throughput continuous flow femtosecond laser-assisted cell optoporation and transfection.we present a femtosecond-laser based nanoprocessing system for transient optical cell membrane poration to allow the introduction of foreign molecules into the interior of a cell with very high throughput. in the setup, cells flow through a micro-flow tube for spatial confinement and are simultaneously targeted by fs laser radiation. beam-shaping generates a focal geometry along a line which is scanned across the micro-flow cell to increase the number of reachable cells. successful cell membrane ...201425123087
xrcc2 rs3218536 polymorphism decreases the sensitivity of colorectal cancer cells to poly(adp-ribose) polymerase 1 inhibitor.single nucleotide polymorphisms (snps) are associated with the development of certain types of cancer. the present study aimed to investigate the association between x-ray repair complementing defective repair in chinese hamster cells 2 (xrcc2) snps and colorectal cancer (crc) cell sensitivity to the poly(adp-ribose) polymerase (parp) 1 inhibitor olaparib (azd2281). snapshot(®) analysis of xrcc2 snps was performed in five crc cell lines. the azd2281-sensitivities of the crc cells were also analy ...201425120693
differential complement activation pathways promote c3b deposition on native and acetylated ldl thereby inducing lipoprotein binding to the complement receptor 1.lipoproteins can induce complement activation resulting in opsonization and binding of these complexes to complement receptors. we investigated the binding of opsonized native ldl and acetylated ldl (acldl) to the complement receptor 1 (cr1). binding of complement factors c3b, igm, c1q, mannose-binding lectin (mbl), and properdin to ldl and acldl were investigated by elisa. subsequent binding of opsonized ldl and acldl to cr1 on cr1-transfected chinese hamster ovarian cells (cho-cr1) was tested ...201425349208
lqt1 mutations in kcnq1 c-terminus assembly domain suppress iks using different mechanisms.long qt syndrome 1 (lqt1) mutations in kcnq1 that decrease cardiac iks (slowly activating delayed rectifier k(+) current) underlie ventricular arrhythmias and sudden death. lqt1 mutations may suppress iks by preventing kcnq1 assembly, disrupting surface trafficking, or inhibiting gating. we investigated mechanisms underlying how three lqt1 mutations in kcnq1 c-terminus assembly domain (r555h/g589d/l619m) decrease iks in heterologous cells and cardiomyocytes.201425344363
[expression, purification and functional identification of human psmp recombinant protein in chinese hamster ovary cells].to construct a new human chemotactic cytokine psmp eukaryotic expression vector to express psmp in chinese hamster ovary (cho) cells and to obtain the purified recombinant psmp protein for its functional mechanism study.201425331384
mutations of rat surfactant protein a have distinct effects on its glycosylation, secretion, aggregation and degradation.surfactant protein a (sp-a) plays critical roles in the innate immune system and surfactant homeostasis of the lung. mutations in sp-a2 of the carbohydrate recognition domain (crd) impair its glycosylation and are associated with pulmonary fibrosis in humans. we aim to examine how mutations in sp-a that impair its glycosylation affect its biological properties and lead to disease.201425242514
comparison of the biological effects of (18)f at different intracellular levels.we herein examined the biological effects of cells treated with (18)f labeled drugs for positron emission tomography (pet). the relationship between the intracellular distribution of (18)f and levels of damaged dna has yet to be clarified in detail. we used culture cells (chinese hamster ovary cells) treated with two types of (18)f labeled drugs, fluorodeoxyglucose (fdg) and fluorine ion (hf). fdg efficiently accumulated in cells, whereas hf did not. to examine the induction of dna double strand ...201425301551
expression, purification, and characterization of recombinant mouse nerve growth factor in chinese hamster ovary cells.mouse ngf (mngf) extracted from mouse submaxillary gland has been approved on the market in china for treating nerve damage caused by n-hexane poisoning for over a decade, and many researches showed the clinical effectiveness of mngf for the treatment of other nerve system diseases. the extracted mngf have risks of potential viral contamination due to the animal origin. here, we report the successful expression, purification, and characterization of recombinant mngf (rmngf). an expression plasmi ...201425244938
long-qt mutation p.k557e-kv7.1: dominant-negative suppression of iks, but preserved camp-dependent up-regulation.mutations in kcnq1, encoding for kv7.1, the α-subunit of the iks channel, cause long-qt syndrome type 1, potentially predisposing patients to ventricular tachyarrhythmias and sudden cardiac death, in particular, during elevated sympathetic tone. here, we aim at characterizing the p.lys557glu (k557e) kv7.1 mutation, identified in a dutch kindred, at baseline and during (mimicked) increased adrenergic tone.201425139741
a robust transfection reagent for the transfection of cho and hek293 cells and production of recombinant proteins and lentiviral particles - ptg1.bioproduction of recombinant proteins (r-proteins) and recombinant lentiviral particles (r-lentiviral particles) requires robust transfections consisting of efficient protocols that are easy to implement, with good reproducibility for a maximum production of proteins and lentiviral particles in a short time with low cytotoxicity. this study evaluates the capacity of histidinylated polyethyleneimine i (ptg1) to facilitate robust dna transfection, with low cytotoxicity, of chinese hamster ovary (c ...201425215936
effect of peptone feeding on transient gene expression process in cho dg44.transient gene expression (tge) gained popularity over the last decade as a rapid method for the production of milligram to gram quantities of recombinant proteins for preclinical studies in biophama industry. thereby, the optimization of the tge technique for chinese hamster ovary (cho) as the dominant host for the production of biotherapeutics is of great interest to reach the values for human embryo kidney-293 (hek-293) cells in terms of transfection efficiencies and production titers. tge ef ...201425215178
acute toxicity and genotoxicity study of fermented traditional herb formula guibi-tang.guibi-tang (guipi-tang in chinese and kihi-to in japanese) is a multi-herb traditional medicine commonly prescribed to treat psychoneurosis in east asia. although this medicine has been widely used, there is little available information on the safety and toxicity of guibi-tang, especially on the fermented one.201425218323
structure-activity profiles of novel 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolates with modified amino acids for cellular uptake by folate receptors α and β and the proton-coupled folate transporter.structure-activity relationships for cellular uptake and inhibition of cell proliferation were studied for 2-amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolates in which the terminal l-glutamate of the parent structure (7) was replaced by natural or unnatural amino acids. compounds 7 and 10-13 were selectively inhibitory toward folate receptor (fr) α-expressing chinese hamster ovary (cho) cells. antiproliferative effects of compounds 7 and 9-13 toward frα- and frβ-expressing ...201425234128
proteomics analysis of altered cellular metabolism induced by insufficient copper level.insufficient copper level in the mammalian cell culture medium resulted in lactate accumulation while maintaining similar growth and culture viability profiles. label-free, lc-ms/ms-based shotgun proteomics method was applied to compare the protein expression profiles obtained from the cultures exposed to suboptimal copper level to those provided with sufficient amount of copper. under copper deficient condition, a substantial reduction of the protein levels of the multiple subunits of complex i ...201425150618
[expression of neural cell adhesion molecule and modification of its n-glycan in ldld-14 cells].neural cell adhesion molecule (ncam) is a glycoprotein expressing on the surface of neurons, glial cells, bone cells and natural killer cells. ncam plays an important role in the process of cell - cell adhesion and cell migration, and is also a model protein to study polysialic acid. in this paper, ncam gene from mouse mammary gland cells (nmumg) was cloned into eukaryotic expression vectors pcdna3.1(+) and transfected into mutant chinese hamster ovary cells ldld-14. the stable transfection over ...201425212013
structural basis of drugs that increase cardiac inward rectifier kir2.1 currents.we hypothesize that some drugs, besides flecainide, increase the inward rectifier current (ik1) generated by kir2.1 homotetramers (ikir2.1) and thus, exhibit pro- and/or antiarrhythmic effects particularly at the ventricular level. to test this hypothesis, we analysed the effects of propafenone, atenolol, dronedarone, and timolol on kir2.x channels.201425205296
[construction of controlled expression system of class b g-protein coupled receptor pac1].pac1 is the neuropeptide pituitary adenylate cyclase activating polypeptide (pacap) preferring receptor, which belongs to class b g protein-coupled receptors (gpcr) family. pac1 mediates the most effects of pacap as neurotransmitter, neuroregulator and neuroprotectant, while its high expression has close relationship with some physiological and pathological processes such as nerve-injury and tumor. to further understand the function of pac1, a cell line that expressed inducible pac1 was construc ...201425195253
mammalian cell-produced therapeutic proteins: heterogeneity derived from protein degradation.therapeutic glycoproteins, for example, antibodies (abs) and fc fusion proteins when produced in mammalian cells, such as chinese hamster ovary (cho) cells generally exhibit heterogeneity. both the oligosaccharide moiety and the protein moiety contribute to this phenomenon. non-enzymatic and enzymatic pathways of protein fragmentation generate heterogeneity in the polypeptide backbone. in the non-enzymatic pathway, physical and chemical events such as light, oxidation, and others can cause the p ...201425118137
gene expression measurements normalized to cell number reveal large scale differences due to cell size changes, transcriptional amplification and transcriptional repression in cho cells.conventional approaches to differential gene expression comparisons assume equal cellular rna content among experimental conditions. we demonstrate that this assumption should not be universally applied because total rna yield from a set number of cells varies among experimental treatments of the same chinese hamster ovary (cho) cell line and among different cho cell lines expressing recombinant proteins. conventional normalization strategies mask these differences in cellular rna content and, c ...201425194670
fluorescence-based soft sensor for at situ monitoring of chinese hamster ovary cell cultures.multi-wavelength fluorescence spectroscopy was investigated as a potential tool for use in monitoring key process variables that include: viable and dead cells, recombinant protein, glucose, and ammonia concentrations for chinese hamster ovary (cho) cells during cultivation.for the purpose of calibrating the fluorescence-based empirical model, cells were grown in batch mode with different initial glucose and glutamine concentrations.spectrofluorometer settings were optimized to ensure reproducib ...201425097916
chronic atrial fibrillation increases microrna-21 in human atrial myocytes decreasing l-type calcium current.atrial fibrillation is characterized by progressive atrial structural and electrical changes (atrial remodeling) that favor arrhythmia recurrence and maintenance. reduction of l-type ca(2+) current (i(ca,l)) density is a hallmark of the electrical remodeling. alterations in atrial micrornas could contribute to the protein changes underlying atrial fibrillation-induced atrial electrical remodeling. this study was undertaken to compare mir-21 levels in isolated myocytes from atrial appendages obta ...201425107449
glyco-engineering for biopharmaceutical production in moss bioreactors.the production of recombinant biopharmaceuticals (pharmaceutical proteins) is a strongly growing area in the pharmaceutical industry. while most products to date are produced in mammalian cell cultures, namely chinese hamster ovary cells, plant-based production systems gained increasing acceptance over the last years. different plant systems have been established which are suitable for standardization and precise control of cultivation conditions, thus meeting the criteria for pharmaceutical pro ...201425071817
antioxidant potential of sutherlandia frutescens and its protective effects against oxidative stress in various cell cultures.sutherlandia frutescens (l.) r.br. (sf) is a south african plant that is widely used to treat stress, infections, cancer, and chronic diseases, many of which involve oxidative stress. the aim of the study was to quantitatively assess the antioxidant potential of sf extracts in cell-free system as well as in cell lines.201425070435
differential thermodynamic driving force of first- and second-generation antihistamines to determine their binding affinity for human h1 receptors.differential binding sites for first- and second-generation antihistamines were indicated on the basis of the crystal structure of human histamine h1 receptors. in this study, we evaluated differences between the thermodynamic driving forces of first- and second-generation antihistamines for human h1 receptors and their structural determinants. the binding enthalpy and entropy of 20 antihistamines were estimated with the van't hoff equation using their dissociation constants obtained from their ...201425065879
stable overexpression of mir-17 enhances recombinant protein production of cho cells.mirnas negatively regulate gene expression at post-transcriptional level, and consequently play an important role in the control of many cellular pathways. the use of mirnas to engineer chinese hamster ovary (cho) cells is an emerging strategy to improve recombinant protein production. here, we describe the effect of transient and stable mirna overexpression on cho cell phenotype. using an established transient mirna screening protocol, the effects of mir-17, mir-92a and cluster mir17-92a on cho ...201424518263
measurement and control of host cell proteins (hcps) in cho cell bioprocesses.chinese hamster ovary (cho) cells are widely used for the production of biotherapeutic recombinant proteins for a range of molecules including monoclonal antibodies and fc-fusion proteins. regulatory requirements for the final product include the removal of host cell proteins (hcps) to acceptable amounts (<100ppm). recent research has begun to unravel the extent to which upstream process conditions and subsequent product recovery and purification processes impact upon the hcp profile. a number o ...201425032907
optimal production of a fusion protein consisting of a single-chain variable fragment antibody against a tumor-associated antigen and interleukin-2 in fed-batch culture of pichia pastoris.the aim of the present study was to establish the strategy for producing a single-chain variable fragment (scfv) antibody fused with interleulin-2 (il2) by pichia pastoris and to optimize production during fed-batch cultivation in a 5-l fermenter.201425075014
the transcription factor ap-1 regulates monkey 20α-hydroxysteroid dehydrogenase promoter activity in cho cells.monkey 20α-hydroxysteroid dehydrogenase (20α-hsd) is a catabolic enzyme responsible for converting progesterone into biologically inactive 20α-hydroxyprogesterone, thereby playing a key role in the estrous cycle or pregnancy and allowing ovulation and parturition to occur in most mammalian animals. monkey 20α-hsd was highly abundant in ovarian and placental tissues during the pre-ovulation and pre-parturition phase and was primarily localized in the syncytiotrophoblast of the placenta. in this s ...201425073972
treating cell culture media with uv irradiation against adventitious agents: minimal impact on cho performance.sterility of cell culture media is an important concern in biotherapeutic processing. in large scale biotherapeutic production, a unit contamination of cell culture media can have costly effects. ultraviolet (uv) irradiation is a sterilization method effective against bacteria and viruses while being non-thermal and non-adulterating in its mechanism of action. this makes uv irradiation attractive for use in sterilization of cell culture media. the objective of this study was to evaluate the effe ...201425044686
progesterone receptor membrane component 1 is a functional part of the glucagon-like peptide-1 (glp-1) receptor complex in pancreatic β cells.glucagon-like peptide-1 (glp-1) is an incretin hormone that regulates glucose homeostasis. because of their direct stimulation of insulin secretion from pancreatic β cells, glp-1 receptor (glp-1r) agonists are now important therapeutic options for the treatment of type 2 diabetes. to better understand the mechanisms that control the insulinotropic actions of glp-1, affinity purification and mass spectrometry (ap-ms) were employed to uncover potential proteins that functionally interact with the ...201425044020
a strategy for fusion expression and preparation of functional glucagon-like peptide-1 (glp-1) analogue by introducing an enterokinase cleavage site.kglp-1, a 31-amino acid glucagon-like peptide-1 (glp-1) analogue, has a great therapeutic potential for anti-diabetes. in this work, a strategy for expression and purification of functional kglp-1 peptide has been established. kglp-1 cdna was fused with glutathione s-transferase (gst), with an enterokinase cleavage site in the fusion junction. the recombinant fusion protein gst-kglp-1 was affinity purified via the gst-tag, and then digested with enterokinase. the resulting gst part as well as th ...201424737080
ultrasound driven assembly of lignin into microcapsules for storage and delivery of hydrophobic molecules.oil-filled microcapsules of kraft lignin were synthesized by first creating an oil in water emulsion followed by a high-intensity, ultrasound-assisted cross-linking of lignin at the water/oil interface. the rationale behind our approach is based on promoting documented lignin hydrophobic interactions within the oil phase, followed by locking the resulting spherical microsystems by covalent cross-linking using a high intensity ultrasound treatment. as further evidence in support of our rationale, ...201424720505
evaluation of anti-inflammatory and mechanism of action of extract of macrosiphonia longiflora (desf.) müll. arg.macrosiphonia longiflora (desf.) müll. arg (apocynaceae), popularly known as 'velame' and 'velame branco', is a native subshrub that grows in the brazilian cerrado. this plant is widely used in traditional medicine in the form of decoction and infusion, particularly as anti-inflammatory, depurative, anti-rheumatic, antisyphilitic and antiulcer remedy. there is no available information in the literature that has addressed its pharmacological activity and phytochemical analysis.201424681039
synthesis, spectral characterization, and antiproliferative studies of mixed ligand titanium complexes of adamantylamine.titanium complexes have been synthesized by the reaction between titanium tetrachloride (ticl4), respective bidentate ligand [4,4' -dimethoxy-2,2' -bipyridine (bpome), 6,6'-dimethyl-2,2'-bipyridine (dpme), 1,2-diaminocyclohexane (dach), 1,10-phenanthroline (phen), and benzoylacetone (bzac)], and adamantylamine (ada) in 1 : 2 : 2 molar ratios, respectively. the structure of synthesized complexes was confirmed using elemental analysis, ftir, uv-visible, (1)h nmr, and mass spectrometry techniques. ...201424715822
surfactant uptake dynamics in mammalian cells elucidated with quantitative coherent anti-stokes raman scattering microspectroscopy.the mechanism of surfactant-induced cell lysis has been studied with quantitative coherent anti-stokes raman scattering (cars) microspectroscopy. the dynamics of surfactant molecules as well as intracellular biomolecules in living chinese hamster lung (chl) cells has been examined for a low surfactant concentration (0.01 w%). by using an isotope labeled surfactant having cd bonds, surfactant uptake dynamics in living cells has been traced in detail. the simultaneous cars imaging of the cell itse ...201424710120
microrna-9 and microrna-326 regulate human dopamine d2 receptor expression, and the microrna-mediated expression regulation is altered by a genetic variant.the human dopamine receptor d2 (drd2) has been implicated in the pathophysiology of schizophrenia and other neuropsychiatric disorders. most antipsychotic drugs influence dopaminergic transmission through blocking dopamine receptors, primarily drd2. we report here the post-transcriptional regulation of drd2 expression by two brain-expressed micrornas (mirs), mir-326 and mir-9, in an ex vivo mode, and show the relevance of mir-mediated drd2 expression regulation in human dopaminergic neurons and ...201424675081
modulation of amyloid precursor protein expression reduces β-amyloid deposition in a mouse model.proteolytic cleavage of the amyloid precursor protein (app) generates β-amyloid (aβ) peptides. prolonged accumulation of aβ in the brain underlies the pathogenesis of alzheimer disease (ad) and is regarded as a principal target for development of disease-modifying therapeutics.201424687915
analyzing clonal variation of monoclonal antibody-producing cho cell lines using an in silico metabolomic platform.monoclonal antibody producing chinese hamster ovary (cho) cells have been shown to undergo metabolic changes when engineered to produce high titers of recombinant proteins. in this work, we have studied the distinct metabolism of cho cell clones harboring an efficient inducible expression system, based on the cumate gene switch, and displaying different expression levels, high and low productivities, compared to that of the parental cells from which they were derived. a kinetic model for cho cel ...201424632968
promiscuous gating modifiers target the voltage sensor of k(v)7.2, trpv1, and h(v)1 cation channels.some of the fascinating features of voltage-sensing domains (vsds) in voltage-gated cation channels (vgccs) are their modular nature and adaptability. here we examined the vsd sensitivity of different vgccs to 2 structurally related nontoxin gating modifiers, nh17 and nh29, which stabilize k(v)7.2 potassium channels in the closed and open states, respectively. the effects of nh17 and nh29 were examined in chinese hamster ovary cells transfected with transient receptor potential vanilloid 1 (trpv ...201424599966
a high throughput screening assay system for the identification of small molecule inhibitors of gsp.mis-sense mutations in the α-subunit of the g-protein, gsα, cause fibrous dysplasia of bone/mccune-albright syndrome. the biochemical outcome of these mutations is constitutively active gsα and increased levels of camp. the aim of this study was to develop an assay system that would allow the identification of small molecule inhibitors specific for the mutant gsα protein, the so-called gsp oncogene. commercially available chinese hamster ovary cells were stably transfected with either wild-type ...201424667240
setting time affects in vitro biological properties of root canal sealers.biocompatibility of root canal sealers is important because of the long-term contact of their eluates and/or degradation products with periapical tissues. the literature still lacks studies about the genotoxic effects of these materials and the influence of setting time on biological properties. the cytotoxicity and genotoxicity of an epoxy resin-based sealer (ah plus), a single methacrylate-based sealer (endorez), and a silicone-based sealer (roekoseal) were assessed.201424666905
association study of c.910a>g and c.1686c>g polymorphisms in xrcc1 gene with risk of hepatocellular carcinoma in the chinese population.xrcc1 (human x-ray repair complementing defective repair in chinese hamster cell 1) gene is considered a potentially important gene influencing the risk of hepatocellular carcinoma (hcc). our analyses detected two allelic variants of xrcc1, c.910a>g and c.1686c>g. we aimed to investigate whether these polymorphisms influence the risk of hcc. the association between the xrcc1 polymorphisms and the risk of hcc was analyzed in 719 patients and 662 controls by polymerase chain reaction-restriction f ...201424634229
pathogenic strains of acanthamoeba are recognized by tlr4 and initiated inflammatory responses in the cornea.free-living amoebae of the acanthamoeba species are the causative agent of acanthamoeba keratitis (ak), a sight-threatening corneal infection that causes severe pain and a characteristic ring-shaped corneal infiltrate. innate immune responses play an important role in resistance against ak. the aim of this study is to determine if toll-like receptors (tlrs) on corneal epithelial cells are activated by acanthamoeba, leading to initiation of inflammatory responses in the cornea. human corneal epit ...201424633052
solvation dynamics and intermittent oscillation of cell membrane: live chinese hamster ovary cell.dynamics of the exofacial thiols (i.e., cell surface thiol containing membrane proteins) of a live chinese hamster ovary (cho) cell is probed by time-resolved confocal microscopy. for this purpose, a fluorescent probe, 7-(diethylamino)-3-(4-maleimidophenyl)-4-methylcoumarin (cpm) is covalently attached to the exofacial thiols. the emission maximum of cpm bound exofacial thiols indicates a highly exposed and polar environment. using cpm, we studied solvation dynamics, for the first time, at the m ...201424571625
heat exposure enhances radiosensitivity by depressing dna-pk kinase activity during double strand break repair.from the role of double strand dna dependent protein kinase (dna-pkcs) activity of non-homologous end joining (nhej) repair for dna double strand breaks (dsbs), we aim to define possible associations between thermo-sensitisation and the enzyme activities in x-ray irradiated cells.201424571173
mir-7 inhibits colorectal cancer cell proliferation and induces apoptosis by targeting xrcc2.analysis using publicly available algorithms predicts that x-ray repair complementing defective repair in chinese hamster cells 2 (xrcc2), a key component in the homologous recombination repair pathway, is a potential target of micro-ribonucleic acid-7 (mir-7). some studies have shown that both mir-7 and xrcc2 are associated with cancer development. for this purpose, we searched for the possible relationship between mir-7 and xrcc2 in the development of colorectal cancer (crc).201424570594
apoptosis-inducing activity of hplc fraction from voacanga globosa (blanco) merr. on the human colon carcinoma cell.voacanga globosa (blanco), a plant endemic to the philippines, is traditionally used especially by indigenous people of bataan in the treatment of ulcers, wounds and tumorous growths. this study aimed to provide scientific evidence to therapeutic properties by determining cytotoxic and pro-apoptotic activity of hplc fractions from leaves on hct116 human colon carcinoma and a549 human lung carcinoma cell lines. ethanolic extraction was performed on v globosa leaves followed by hexane and ethyl ac ...201424568467
improved expression of recombinant human factor ix by co-expression of ggcx, vkor and furin.recombinant human fix concentrates (rhfix) are essential in the treatment and prevention of bleeding in the bleeding disorder haemophilia b. however, due to the complex nature of fix production yields are low which leads to high treatment costs. here we report the production of rhfix with substantially higher yield by co-expressing human fix with ggcx (γ-glutamyl carboxylase), vkor (vitamin k epoxide reductase) and furin (paired basic amino acid cleaving enzyme) in chinese hamster ovary (cho) ce ...201424567122
[study on the effect of deficient ercc2/xpd gene on the repair of dna damage induced by uvc in cho cell line].to explore the function of ercc2/xpd in the repair of dna damage induced by uvc.201424564106
a phase i/ii, multiple-dose, dose-escalation study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with advanced solid tumors.this phase i/ii study evaluated safety, efficacy, and pharmacokinetics of escalating, multiple doses of siltuximab, a chimeric anti-interleukin (il)-6 monoclonal antibody derived from a new chinese hamster ovary (cho) cell line in patients with advanced/refractory solid tumors.201424563479
neonatal genome-wide methylation patterns in relation to birth weight in the norwegian mother and child cohort.although epigenetic regulation plays a critical role in embryonic development, few studies have examined the relationship of epigenome-wide methylation with fetal growth. using the infinium humanmethylation450 beadchip (illumina, inc., san diego, california) in a substudy of 1,046 infants from the norwegian mother and child cohort study (moba) enrolled between 1999 and 2008, we examined epigenome-wide cord blood dna methylation in relation to birth weight. in multivariable-adjusted robust linear ...201424561991
the impact of homologous recombination repair deficiency on depleted uranium clastogenicity in chinese hamster ovary cells: xrcc3 protects cells from chromosome aberrations, but increases chromosome fragmentation.depleted uranium (du) is extensively used in both industry and military applications. the potential for civilian and military personnel exposure to du is rising, but there are limited data on the potential health hazards of du exposure. previous laboratory research indicates du is a potential carcinogen, but epidemiological studies remain inconclusive. du is genotoxic, inducing dna double strand breaks, chromosome damage and mutations, but the mechanisms of genotoxicity or repair pathways involv ...201424561002
long-term activation upon brief exposure to xanomleline is unique to m1 and m4 subtypes of muscarinic acetylcholine receptors.xanomeline is an agonist endowed with functional preference for m1/m4 muscarinic acetylcholine receptors. it also exhibits both reversible and wash-resistant binding to and activation of these receptors. so far the mechanisms of xanomeline selectivity remain unknown. to address this question we employed microfluorometric measurements of intracellular calcium levels and radioligand binding to investigate differences in the short- and long-term effects of xanomeline among muscarinic receptors expr ...201424558448
expression of base excision repair key factors and mir17 in familial and sporadic breast cancer.understanding of brca1/2 interaction with the base excision repair (ber) pathway could improve therapy based on 'synthetic lethality', whose effectiveness is based on homologous recombination deficiency in cells lacking functional brca genes. however, poly (adp-ribose) polymerase (parp) inhibitors failed in some patients and for this reason we explored ber key enzyme expression. in this study, the expression of ber enzymes (redox factor 1/apurinic-apyrimidinic endonuclease 1 (ref1/apex1), nth en ...201424556691
profiling convoluted single-dimension proton nmr spectra: a plackett-burman approach for assessing quantification error of metabolites in complex mixtures with application to cell culture.single-dimension hydrogen, or proton, nuclear magnetic resonance spectroscopy (1d-(1)h nmr) has become an attractive option for characterizing the full range of components in complex mixtures of small molecular weight compounds due to its relative simplicity, speed, spectral reproducibility, and noninvasive sample preparation protocols compared to alternative methods. one challenge associated with this method is the overlap of nmr resonances leading to "convoluted" spectra. while this can be mit ...201424555717
effect of brazilian propolis (af-08) on genotoxicity, cytotoxicity and clonogenic death of chinese hamster ovary (cho-k1) cells irradiated with (60)co gamma-radiation.the present study was conducted in order to evaluate the effect of brazilian propolis (af-08; 5, 10, 15, 30, 50, 100, and 200μg/ml) in protecting cho-k1 cells against genotoxic and cytotoxic damage and clonogenic death induced by (60)co gamma-radiation (1.0, 2.0, 4.0, and 6.0gy). for this purpose, three interlinked endpoints were analyzed: induction of dna damage by use of the micronucleus (mn) test (genotoxic damage), cell viability by means of the mts assay, and differential staining (cytotoxi ...201424525380
metabolic control at the cytosol-mitochondria interface in different growth phases of cho cells.metabolism at the cytosol-mitochondria interface and its regulation is of major importance particularly for efficient production of biopharmaceuticals in chinese hamster ovary (cho) cells but also in many diseases. we used a novel systems-oriented approach combining dynamic metabolic flux analysis and determination of compartmental enzyme activities to obtain systems level information with functional, spatial and temporal resolution. integrating these multiple levels of information, we were able ...201424525334
4-hydroxynonenal induces an increase in expression of receptor for activating c kinase 1 (rack1) in chinese hamster v79-4 lung cells.4-hydroxy-trans-2-nonenal (hne) is a cytotoxic α,β-unsaturated aldehyde implicated in the pathology of several diseases that have an oxidative stress mechanism, including atherosclerosis, diabetes, alcohol-induced liver disease, and neurodegenerative disorders. as the most toxic aldehydic product of lipid peroxidation, hne is known to exert a range of biological effects in a concentration-dependent manner. in this study, the effect of hne on the levels of proteins in v79-4 chinese hamster lung c ...201424525193
cellular and genomic toxicity produced by uv light in chinese hamster ovary cells.uvb and uvc toxicity was detected in chinese hamster ovary (cho) cell lines aa8, uv5 and xem2 (a v79-derived cell line expressing rat p450 1a1). unlike ficz-hplc assay that showed induction of cyp1a1 enzyme activity after 20 minutes and 2 hour uvc exposure, the erod assay showed no difference in cytochrome p450 1a1 (cyp1a1) activity after exposure to different doses of uvb and uvc light. different cytotoxic and mutagenic effect of photo lesions induced by uvc and uvb light was investigated with ...201424577918
efficiency improvement of an antibody production process by increasing the inoculum density.increasing economic pressure is the main driving force to enhance the efficiency of existing processes. we developed a perfusion strategy for a seed train reactor to generate a higher inoculum density for a subsequent fed batch production culture. a higher inoculum density can reduce culture duration without compromising product titers. hence, a better capacity utilization can be achieved. the perfusion strategy was planned to be implemented in an existing large scale antibody production process ...201424574274
black pepper constituent piperine: genotoxicity studies in vitro and in vivo.piperine is responsible for the hot taste of black pepper. publications on genotoxicity of piperine are reported: negative ames tests and one in vitro micronucleus test (mnt). in vivo tests were mainly negative. in the majority of the data the administered dose levels did not follow the dose selection requirements of regulatory guidelines of having dose levels up to the maximum tolerated dose (mtd). the only oral high dose studies were a positive in vivo mnt in mice in contrast to a negative in ...201424525095
high-throughput clonepix fl analysis of mab-expressing clones using the ucoe expression system.therapeutic recombinant monoclonal antibodies (mabs) are commonly produced by high-expressing, clonal, mammalian cells. creation of these clones for manufacturing remains heavily reliant on stringent selection and gene amplification, which in turn can lead to genetic instability, variable expression, product heterogeneity and prolonged development timelines. inclusion of cis-acting ubiquitous chromatin opening elements (ucoe™) in mammalian expression vectors has been shown to improve productivit ...201424518824
pharmacological characterization of endomorphin-2-based cyclic pentapeptides with methylated phenylalanine residues.as part of our continuing studies on the structure-activity relationships of cyclic pentapeptides based on the structure of endomorphin-2, we report here the synthesis and biological activities of a new series of analogs incorporating 2', 3' or 4'-methylphenylalanine (mephe) residues into positions 3 or 4 of the parent cyclopeptide, dmt-c[d-lys-phe-phe-asp]nh2 (dmt=2',6'-dimethyltyrosine). analogs with mephe in position 4 showed a row of magnitude increased μ-opioid receptor (mop receptor) affin ...201424632335
a real-time method for measuring camp production modulated by gαi/o-coupled metabotropic glutamate receptors.group ii and group iii metabotropic glutamate (mglu) receptors are g protein-coupled receptors (gpcrs) that inhibit adenylyl cyclase via activation of gαi/o. the purpose of this study was to design a universal method that overcomes previous challenges in consistently measuring group ii and group iii mglu-receptor (mglur) activation in stably transfected systems. in chinese hamster ovary (cho) cells stably transfected with the glosensor camp biosensor, we optimized conditions for simple and highl ...201424659805
a novel luminescence-based method for the detection of functionally active antibodies to muscarinic acetylcholine receptors of the m3 type (machr3) in patients' sera.in different bioassays, functional antibodies reacting with the human muscarinic acetylcholine receptor m3(machr3) have been detected in sera from patients with sjögren's syndrome (ss), and there is strong evidence that those antibodies may have pathogenetic relevance. however, depending on the method of detection, their prevalence varied. furthermore, those bioassays are difficult to standardize. we report on the development and optimization of a novel test system based on a luminometric method ...201424628494
the brca2 gene is a potential molecular target during 5-fluorouracil therapy in human oral cancer cells.5-fluorouracil (5-fu) is widely used in clinical cancer therapy. it is commonly used either alone or in combination with other drugs and/or radiation for head and neck, and other types of cancers. 5-fu induces dna double-strand breaks (dsbs). inhibition of the repair of 5-fu-induced dsbs may improve the therapeutic response in many tumors to this anticancer agent. the aim of the present study was to further our understanding of the pathways which are involved in the repair of 5-fu-induced dsbs. ...201424627042
disruption of the actin cortex contributes to susceptibility of mammalian cells to nanosecond pulsed electric fields.nanosecond pulsed electric fields (nspefs) perturb membranes of cultured mammalian cells in a dose-dependent manner with different types of cells exhibiting characteristic survivability. adherent cells appear more robust than non-adherent cells during whole-cell exposure. we hypothesize that cellular elasticity based upon the actin cytoskeleton is a contributing parameter, and the alteration of a cell's actin cortex will significantly affect viability upon nspef exposure. chinese hamster ovary ( ...201424619788
confocal imaging with a fluorescent bile acid analogue closely mimicking hepatic taurocholate disposition.this study aimed to characterize the in vitro hepatic transport mechanisms in primary rat and human hepatocytes of the fluorescent bile acid derivative n-(24-[7-(4-n,n-dimethylaminosulfonyl-2,1,3-benzoxadiazole)]amino-3α,7α,12α-trihydroxy-27-nor-5β-cholestan-26-oyl)-2'-aminoethanesulfonate (tauro-nor-thca-24-dbd), previously synthesized to study the activity of the bile salt export pump (bsep). the fluorescent bile acid derivative exhibited saturable uptake kinetics in suspended rat hepatocytes. ...201424652646
role of oatp-1b1 and/or oatp-1b3 in hepatic disposition of tyrosine kinase inhibitors.the metabolism of tyrosine kinase inhibitors (tkis) is mainly mediated via hepatic route, but the mechanism responsible for their hepatocellular accumulation is still unknown. this study was designed to understand the contribution of organic anion transporting polypeptides (oatps) in the hepatic uptake of selected tkis - pazopanib, canertinib, erlotinib, vandetanib and nilotinib.201424643910
cell compatible arginine containing cationic polymer: one-pot synthesis and preliminary biological assessment.synthetic cationic polymers are of interest as both nonviral vectors for intracellular gene delivery and antimicrobial agents. for both applications synthetic polymers containing guanidine groups are of special interest since such kind of organic compounds/polymers show a high transfection potential along with antibacterial activity. it is important that the delocalization of the positive charge of the cationic group in guanidine significantly decreases the toxicity compared to the ammonium func ...201424619618
efficient folding/assembly in chinese hamster ovary cells is critical for high quality (low aggregate content) of secreted trastuzumab as well as for high production: stepwise multivariate regression analyses.when developing cell culture processes for therapeutic antibodies, the low content of aggregated proteins is the most critical because administering aggregated antibody molecules might result in adverse effects such as immunogenicity. to characterize cells with high productivity and quality, we determined factors that are closely related to antibody titer, which is a productivity indicator, and the area percentage of high molecular weight species in cultivated media, which is equivalent to aggre ...201424635945
turoctocog alfa for the treatment of hemophilia a.patients with hemophilia a lack functional coagulation factor viii (fviii), causing excessive spontaneous bleeding episodes and bleeding during trauma or surgery. plasma-derived or synthetic recombinant fviii is used to control bleeding, but currently available treatments are limited because of patient development of fviii inhibitors and cross-contamination of human and animal-derived infectious agents. turoctocog alfa is a recombinant fviii produced in chinese hamster ovary cells that has demon ...201424619589
efficient production and purification of extracellular domain of human fgfr-fc fusion proteins from chinese hamster ovary cells.the family of fibroblast growth factor receptors (fgfrs) plays an important role in cell growth, survival, differentiation and angiogenesis. the three immunoglobulin-like extracellular domains of fgfr (d1, d2, and d3) are critical for ligand binding and specificity towards fibroblast growth factor and heparan sulfate. fibroblast growth factor receptors are overexpressed in a wide variety of tumors, such as breast, bladder, and prostate cancer, and therefore they are attractive targets for differ ...201424727156
optimization of heterologous protein production in chinese hamster ovary cells under overexpression of spliced form of human x-box binding protein.the optimization of protein production is a complex and challenging problem in biotechnology. different techniques for transcription, translation engineering and the optimization of cell culture conditions have been used to improve protein secretion, but there remain many open problems involving post-translational modifications of the secreted protein and cell line stability.201424725707
effect of glutamine substitution by tca cycle intermediates on the production and sialylation of fc-fusion protein in chinese hamster ovary cell culture.in an effort to reduce the accumulation of ammonia in culture medium, three different tca cycle intermediates, (alpha-ketoglutarate (α-kg), citric acid and succinic acid) along with glutamic acid for a comparison, were examined as a substitute for glutamine with rcho cell line producing a fc-fusion glycoprotein. among them, α-kg showed the best production performance. when cells were cultivated with 4 mm α-kg, the final ammonia concentration did not exceed 3 mm, which is less than one fourth of ...201424721212
high-throughput screening platform for engineered nanoparticle-mediated genotoxicity using cometchip technology.the likelihood of intentional and unintentional engineered nanoparticle (enp) exposure has dramatically increased due to the use of nanoenabled products. indeed, enps have been incorporated in many useful products and have enhanced our way of life. however, there are many unanswered questions about the consequences of nanoparticle exposures, in particular, with regard to their potential to damage the genome and thus potentially promote cancer. in this study, we present a high-throughput screenin ...201424617523
transcriptome analyses of cho cells with the next-generation microarray cho41k: development and validation by analysing the influence of the growth stimulating substance igf-1 substitute longr(3.).the increasing importance of chinese hamster ovary (cho) cells for the production of pharmaceutical proteins has awakened the demand to understand the cellular metabolism of these cells. however, satisfactory gene expression studies have yet been impractical due to insufficient coverage of sequences. in this work, previously determined sequence information of cho cells and newly derived data from 454 and illumina sequencing was used to establish the cho41k microarray which contains 41,304 probes ...201424613301
presenilin-1 influences processing of the acetylcholinesterase membrane anchor prima.presenilin-1 (ps1) is the catalytic component of the γ-secretase complex. in this study, we explore if ps1 participates in the processing of the cholinergic acetylcholinesterase (ache). the major ache variant expressed in the brain is a tetramer (g(4)) bound to a proline-rich membrane anchor (prima). overexpression of the transmembrane prima protein in chinese hamster ovary cells expressing ache and treated with the γ-secretase inhibitor n-[n-(3,5-difluorophenacetyl)-l-alanyl]-s-phenylglycine t- ...201424612677
occurrence and subcellular distribution of the nadphx repair system in mammals.hydration of nad(p)h to nad(p)hx, which inhibits several dehydrogenases, is corrected by an atp-dependent dehydratase and an epimerase recently identified as the products of the vertebrate carkd (carbohydrate kinase domain) and aibp (apolipoprotein ai-binding protein) genes respectively. the purpose of the present study was to assess the presence of these enzymes in mammalian tissues and determine their subcellular localization. the carkd gene encodes proteins with a predicted mitochondrial prop ...201424611804
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