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chromosomal instability and cytotoxicity induced by ribavirin: comparative analysis in cell lines with different drug-metabolizing profiles.ribavirin is an important component of the treatment for hepatitis c virus (hcv) infection and, in combination with the new direct-acting antiviral (daa) agents, comprises the major current therapeutic regimens. this study evaluated the cytotoxicity and chromosomal instability induced by ribavirin using the in vitro cytokinesis-block micronucleus cytome (cbmn-cyt) assay in two cell lines with different expression levels of drug-metabolizing enzymes: human hepatocellular carcinoma cells (hepg2) a ...201729199475
hypersensitivity of brca2 deficient cells to rosemary extract explained by weak parp inhibitory activity.rosemary extract is used in food additives and traditional medicine and has been observed to contain anti-tumor activity. in this study, rosemary extract is hypothesized to induce synthetic lethality in brca2 deficient cells by parp inhibition. chinese hamster lung v79 cells and its mutant cell lines, v-c8 (brca2 deficient) and v-c8 with brca2 gene correction were used. rosemary extract and its major constituent chemicals were tested for their cytotoxicity by colony formation assay in cells of d ...201729196727
amp and adenosine are both ligands for adenosine 2b receptor signaling.adenosine is considered the canonical ligand for the adenosine 2b receptor (a2br). a2br is upregulated following kidney ischemia augmenting post ischemic blood flow and limiting tubular injury. in this context the beneficial effect of a2br signaling has been attributed to an increase in the pericellular concentration of adenosine. however, following renal ischemia both kidney adenosine monophosphate (amp) and adenosine levels are substantially increased. using computational modeling and calcium ...201829191553
enhanced igg1 production by overexpression of nuclear factor kappa b inhibitor zeta (nfkbiz) in chinese hamster ovary cells.several engineering strategies have been employed to improve the production of therapeutic recombinant proteins in chinese hamster ovary (cho) cell lines. we have focused on unfolded protein response-based engineering and reported that atf4 overexpression increases protein production. in this study, transcriptome analysis of atf4-overexpressed cho cells was performed using high-coverage expression profiling, to search for another key factor contributing to recombinant protein production. we obse ...201729188404
observability of complex systems: finding the gap.for a reconstruction of state and parameter values in a dynamic system model, first the question whether these values can be uniquely determined from the data must be answered. this structural model property is known as observability or, in case of parameter calibration only, identifiability. testing a given model for observability is a well studied problem in the systems and control sciences. however, it is increasingly difficult, if not impossible, to address this property for large size model ...201729185491
combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models.chromosome transfer technology, including chromosome modification, enables the introduction of mb-sized or multiple genes to desired cells or animals. this technology has allowed innovative developments to be made for models of human disease and humanized animals, including down syndrome model mice and humanized transchromosomic (tc) immunoglobulin mice. genome editing techniques are developing rapidly, and permit modifications such as gene knockout and knockin to be performed in various cell li ...201829180645
astrocytic γ-aminobutyric acid (gaba) transporters mediate guanidinoacetate transport in rat brain.guanidinoacetate (gaa) is a biosynthetic precursor of creatine, which plays a critical role in homeostasis of high-energy phosphates in the brain, but cerebral accumulation of gaa leads to neurological complications, such as epilepsy and seizures. the purpose of the present study was to clarify the contribution of the γ-aminobutyric acid (gaba) transport systems to gaa transport in astrocytes by means of uptake studies in rat brain slices, primary astrocyte cultures and chinese hamster ovary (ch ...201729175673
role of 6-o-α-maltosyl-β-cyclodextrin in lysosomal cholesterol deprivation in npc1-deficient chinese hamster ovary cells.we aimed to investigate whether 6-o-α-maltosyl-β-cyclodextrin (mal-βcd) is incorporated into cells and lysosomes during the release of unesterified cholesterol in npc1-deficient chinese hamster ovary (cho) cells (npc1 ko cells) and cho-jp17 cells (jp17 cells). internalization of mal-βcd in cells and lysosomes and extracellular release of lysosomal unesterified cholesterol were demonstrated by lc/ms/ms and lc/ms, respectively. internalization of mal-βcd was greater in npc1 ko cells than in jp17 c ...201829172126
formulation and characterization of poly(propylacrylic acid)/poly(lactic-co-glycolic acid) blend microparticles for ph-dependent membrane disruption and cytosolic delivery.poly(lactic-co-glycolic acid) (plga) is widely used as a vehicle for delivery of pharmaceutically relevant payloads. plga is readily fabricated as a nano- or microparticle (mp) matrix to load both hydrophobic and hydrophilic small molecular drugs as well as biomacromolecules such as nucleic acids and proteins. however, targeting such payloads to the cell cytosol is often limited by mp entrapment and degradation within acidic endolysosomes. poly(propylacrylic acid) (ppaa) is a polyelectrolyte pol ...201729164777
an endogenous retroviral envelope syncytin and its cognate receptor identified in the viviparous placental mabuya lizard.syncytins are envelope genes from endogenous retroviruses that have been captured during evolution for a function in placentation. they have been found in all placental mammals in which they have been searched, including marsupials. placental structures are not restricted to mammals but also emerged in some other vertebrates, most frequently in lizards, such as the viviparous mabuya scincidae. here, we performed high-throughput rna sequencing of a mabuya placenta transcriptome and screened for t ...201729162694
a novel mutation in the fibrinogen bβ chain (c.490g>a; end of exon 3) causes a splicing abnormality and ultimately leads to congenital hypofibrinogenemia.we found a novel heterozygous mutation in the fibrinogen bβ chain (c.490g>a) of a 3-year-old girl with congenital hypofibrinogenemia. to clarify the complex genetic mechanism, we made a mini-gene including a fgb c.490g>a mutation region, transfected it into a chinese hamster ovary (cho) cell line, and analyzed reverse transcription (rt) products. the assembly process and secretion were examined using recombinant mutant fibrinogen. direct sequencing demonstrated that the mutant rt product was 99 ...201729156616
sustaining an efficient and effective cho cell line development platform by incorporation of 24-deep well plate screening and multivariate analysis.efficient and effective cell line screening is paramount toward a successful biomanufacturing program. here we describe the implementation of 24-deep well plate (24-dwp) screening of cho lines as part of the cell line development platform at abbvie. incorporation of this approach accelerated the identification of the best candidate lines for process development. in an effort to quantify and predict process performance comparability, we compared cell culture performance in and in shake flasks, fo ...201729150912
novel intracellular transport-refractory mutations in kcnh2 identified in patients with symptomatic long qt syndrome.missense mutations in kcnh2, a gene encoding the kv11.1 channel, cause long qt syndrome (lqts) type 2 primarily by disrupting the intracellular transport of kv11.1 to the plasma membrane. the present study aimed to clarify the functional changes by two novel kcnh2 missense mutations.201729146210
engineered and natural promoters and chromatin-modifying elements for recombinant protein expression in cho cells.promoters play a pivotal role in integrating and processing the signals related to transcription initiation. strong natural viral promoters, such as hcmv or sv40e, have been routinely employed to achieve a high rate of gene expression in ubiquitously used chinese hamster ovary (cho) cells. however, viral promoters are susceptible to epigenetic silencing and lack precise regulation levers. this has paved the way to more sensible control elements: endogenous, inducible, and synthetic promoters. in ...201729145694
calcein release from cells in vitro via reversible and irreversible electroporation.the aim of this study was to investigate the dependence of calcein extraction and cell viability on the parameters of pulsed electric field (pef). two different approaches concerning pef parameters were investigated: (1) extraction efficiency and cell viability dependence on pulse number, exploiting 1200 v/cm 100 µs duration high voltage (hv) electric pulses and (2) extraction efficiency and cell viability dependence on the pulses with different duration (44-400 µs) and electric field strength ( ...201729143077
inhibition of glycation-induced cytotoxicity, protein glycation, and activity of proteolytic enzymes by extract from perovskia atriplicifolia roots.protein glycation and glycotoxicity belong to the main oxidative-stress related complications in diabetes. perovskia species are used in asian folk medicine as antidiabetic herbs.201729142432
mild heat induces a distinct "eustress" response in chinese hamster ovary cells but does not induce heat shock protein synthesis.the current research on cellular heat stress management focuses on the roles of heat shock proteins (hsps) and the proteostasis network under severe stress conditions. the mild, fever-type stress and the maintenance of membrane homeostasis are less well understood. herein, we characterized the acute effect of mild, fever-range heat shock on membrane organization, and hsp synthesis and localization in two mammalian cell lines, to delineate the role of membranes in the sensing and adaptation to he ...201729142280
proteomic analysis of cho cell lines producing high and low quantities of a recombinant antibody before and after selection with methotrexate.high levels of recombinant protein production in chinese hamster ovary (cho) cells can be achieved by amplification of transgenes using the dihydrofolate reductase/methotrexate (dhfr/mtx) system. with the aim to identify predictive markers enabling the preselection of suitable high producing clones we investigated the impact of mtx-based gene amplification on two cho cells lines producing different levels of a human monoclonal antibody by carrying out a comparative proteome analysis. the differe ...201829137976
dietary k+ and cl- independently regulate basolateral conductance in principal and intercalated cells of the collecting duct.the renal collecting duct contains two distinct cell types, principal and intercalated cells, expressing potassium kir4.1/5.1 (kcnj10/16) and chloride clc-k2 (clc-kb in humans) channels on their basolateral membrane, respectively. both channels are thought to play important roles in controlling systemic water-electrolyte balance and blood pressure. however, little is known about mechanisms regulating activity of kir4.1/5.1 and clc-k2/b. here, we employed patch clamp analysis at the single channe ...201829134279
characterizing steady states of genome-scale metabolic networks in continuous cell cultures.in the continuous mode of cell culture, a constant flow carrying fresh media replaces culture fluid, cells, nutrients and secreted metabolites. here we present a model for continuous cell culture coupling intra-cellular metabolism to extracellular variables describing the state of the bioreactor, taking into account the growth capacity of the cell and the impact of toxic byproduct accumulation. we provide a method to determine the steady states of this system that is tractable for metabolic netw ...201729131817
baicalein reduces oxidative stress in cho cell cultures and improves recombinant antibody productivity.oxidative stress that naturally accumulates in the endoplasmic reticulum (er) as a result of mitochondrial energy metabolism and protein synthesis can disturb the er function. because er have a responsibility on the protein synthesis and quality control of the secreted proteins, er homeostasis has to be well maintained. when h2 o2 , an oxidative stress inducer, is added to recombinant chinese hamster ovary (rcho) cell cultures, it reduced cell growth, monoclonal antibody (mab) production, and ga ...201729125225
towards replacement of the acellular pertussis vaccine safety test: comparison of in vitro cytotoxic activity and in vivo activity in mice.because of the exquisite sensitivity of the murine histamine sensitization test (hist) in detecting minute amounts of active pertussis toxin (ptx), this animal-based test has been used to assure the safety of acellular pertussis vaccines in the united states and other countries around the world. prompted by humane considerations, efforts are underway to find a suitable in vitro replacement assay that has critical attributes comparable to that of the hist. in this study, we compared the sensitivi ...201729122386
using specific recombinant gonadotropins to induce spermatogenesis and spermiation in the european eel (anguilla anguilla).new specific european eel (anguilla anguilla) recombinant gonadotropins (aargths) produced in the ovarian cells of chinese hamsters (cho) were used to induce maturation in captive male eels. in the first experiment, five different hormonal treatments were assayed: one group was given a constant dose of recombinant european eel follicle-stimulating hormone (aarfsh; 4 μg/fish) for 9 weeks, and the second group received a constant dose of recombinant european eel luteinizing hormone (aarlh; 2 μg/fi ...201829120707
tolerability, response and outcome of high-risk neuroblastoma patients treated with long-term infusion of anti-gd2 antibody ch14.18/cho.immunotherapy with short term infusion (sti) of monoclonal anti-gd2 antibody (mab) ch14.18 (4 × 25 mg/m2/d; 8-20 h) in combination with cytokines and 13-cis retinoic acid (ra) prolonged survival in high-risk neuroblastoma (nb) patients. here, we investigated long-term infusion (lti) of ch14.18 produced in chinese hamster ovary cells (ch14.18/cho; 10 × 10 mg/m2; 24 h) in combination with subcutaneous (s.c.) interleukin-2 (il-2) in a single center program and report clinical response, toxicity and ...201829120699
quantifying the potential for bursting bubbles to damage suspended cells.bubbles that rise to the surface of a cell suspension can damage cells when they pop. this phenomenon is particularly problematic in the biotechnology industry, as production scale bioreactors require continuous injection of oxygen bubbles to maintain cell growth. previous studies have linked cell damage to high energy dissipation rates (edr) and have predicted that for small bubbles the edr could exceed values that would kill many cells used in bioreactors, including chinese hamster ovary (cho) ...201729118382
evaluating the toxicity of tio2-based nanoparticles to chinese hamster ovary cells and escherichia coli: a complementary experimental and computational approach.titania-supported palladium, gold and bimetallic nanoparticles (second-generation nanoparticles) demonstrate promising photocatalytic properties. however, due to unusual reactivity, second-generation nanoparticles can be hazardous for living organisms. considering the ever-growing number of new types of nanoparticles that can potentially contaminate the environment, a determination of their toxicity is extremely important. the main aim of presented study was to investigate the cytotoxic effect o ...201729114443
glycan profile of cho derived igm purified by highly efficient single step affinity chromatography.immunoglobulin m (igm) antibodies are reckoned as promising tools for therapy and diagnostic approaches. nevertheless, the commercial success of igms is hampered due to bottlenecks in recombinant production and downstream processing. igms are large, complex and highly glycosylated proteins that are only stable in a limited range of conditions. to investigate these sensitive igm antibodies we optimized the elution conditions for a commercially available igm affinity matrix (captureselect™). apply ...201729106908
cell recognition molecule l1 regulates cell surface glycosylation to modulate cell survival and migration.background: cell recognition molecule l1 (l1) plays an important role in cancer cell differentiation, proliferation, migration and survival, but its mechanism remains unclear. methodology/principal: our previous study has demonstrated that l1 enhanced cell survival and migration in neural cells by regulating cell surface glycosylation. in the present study, we show that l1 affected cell migration and survival in cho (chinese hamster ovary) cell line by modulation of sialylation and fucosylation ...201729104485
functional characterization of the dual allatostatin-a receptors in mosquitoes.the neuropeptide allatostatin-a (asta) and its cognate receptors (astars) are involved in the modulation of feeding behavior, which in hematophagous insects includes the regulation of the disease vector-related behaviors, host seeking and blood feeding. in mosquitoes and other dipterans, there are two copies of astar, contrasting with the single copy found in other insects. in this study, we identified and cloned the dual astar system of two important disease vectors aedes aegypti and culex quin ...201829103918
chemical characterization and cytotoxic, genotoxic, and mutagenic properties of baccharis trinervis (lam, persoon) from colombia and brazil.baccharis trinervis (lam, persoon) leaves are used in the traditional medicine for the treatment of high fevers, edema, inflammation, sores and muscle cramps, snakebites and as antiseptic.201829100934
a novel fc-engineered human icam-1/cd54 antibody with potent anti-myeloma activity developed by cellular panning of phage display libraries.to identify antibodies suitable for multiple myeloma (mm) immunotherapy, a cellular screening approach was developed using plasma cell lines jk-6l and ina-6 and human synthetic single-chain fragment variable (scfv) phage libraries. isolated phage antibodies were screened for myeloma cell surface reactivity. due to its binding characteristics, phage piii-15 was selected to generate the scfv-fc fusion protein tp15-fc with an fc domain optimized for fcγriiia binding. various mm cell lines and patie ...201729100408
optimized selection marker and cho host cell combinations for generating high monoclonal antibody producing cell lines.there are several selection markers which are suitable for generating stably transfected chinese hamster ovary (cho) cell lines. due to their different modes of action, each selection marker has its own optimal selection stringency in different host cells for obtaining high productivity. using an internal ribosome entry site (ires)-mediated tricistronic vector and a set of ires variants with different strengths, the expression of five antibiotics resistance genes (args) in cho-k1 cells and dihyd ...201729090854
construction of mtb72f plasmid as a dna vaccine candidate for mycobacterium tuberculosis.with one-third of the world's population infected, tuberculosis (tb) is one of the most common infectious diseases and a major public health problem, especially in developing countries. the efficacy of the bcg vaccine for controlling the disease in adults is poor. the development of an effective tb vaccine is a global objective. an effective tuberculosis vaccine should stimulate cellular immunity. dna vaccines are a new generation of vaccines with the potential to achieve this goal. the aim of t ...201729090235
cloning and expression of recombinant human interleukin-7 in chinese hamster ovary (cho) cells.the critical role of interleukin-7 (il-7) in homeostatic proliferation and t cell survival has made it a promising cytokine for the treatment of various clinical conditions, especially those associated with lymphopenia.201729090231
magnesium stearate, a widely-used food additive, exhibits a lack of in vitro and in vivo genotoxic potential.magnesium stearate is widely used in the production of dietary supplement and pharmaceutical tablets, capsules and powders as well as many food products, including a variety of confectionery, spices and baking ingredients. although considered to have a safe toxicity profile, there is no available information regarding its potential to induce genetic toxicity. to aid safety assessment efforts, magnesium sulfate was evaluated in a battery of tests including a bacterial reverse mutation assay, an i ...201729090120
the dietary furocoumarin imperatorin increases plasma glp-1 levels in type 1-like diabetic rats.imperatorin, a dietary furocoumarin, is found not only in medicinal plants, but also in popular culinary herbs, such as parsley and fennel. recently, imperatorin has been shown to activate gpr119 in cells. another gpr, gpr131, also called tgr5 or g-protein-coupled bile acid receptor 1 (gpbar1), is known to regulate glucose metabolism. additionally, tgr5 activation increases glucagon-like peptide (glp-1) secretion to lower blood sugar levels in animals. therefore, the present study aims to determ ...201729084156
fluorescent turn-on probes for wash-free mrna imaging via covalent site-specific enzymatic labeling.investigating the many roles rna plays in cellular regulation and function has increased demand for tools to explore rna tracking and localization within cells. our recently reported rna-tag (transglycosylation at guanine) approach uses an rna-modifying enzyme, trna-guanine transglycosylase (tgt), to accomplish covalent labeling of an rna of interest with fluorescent tracking agents in a highly selective and efficient manner. unfortunately, labeling by this method currently suffers from a high n ...201729081948
selenium and zinc against aβ25-35-induced cytotoxicity and tau phosphorylation in pc12 cells and inhibits γ-cleavage of app.amyloid beta (aβ) is the main component of the amyloid plaques that accumulate in the brains of alzheimer patients. the present study was conducted to investigate whether the combined treatment with selenium (se) and zinc (zn) offers more beneficial effects than that provided by either of them alone in reversing aβ25-35-induced neurotoxicity in pc12 cells. cells were pretreated with 0.1 μmol/l of se and zn for 4 h, after treated with 10 mmol/l aβ25-35 for 24 h. cells were divided into control an ...201729081063
human endoglin as a potential new partner involved in platelet-endothelium interactions.complex interactions between platelets and activated endothelium occur during the thrombo-inflammatory reaction at sites of vascular injuries and during vascular hemostasis. the endothelial receptor endoglin is involved in inflammation through integrin-mediated leukocyte adhesion and transmigration; and heterozygous mutations in the endoglin gene cause hereditary hemorrhagic telangiectasia type 1. this vascular disease is characterized by a bleeding tendency that is postulated to be a consequenc ...201729080903
metabolic phenotyping of cho cells varying in cellular biomass accumulation and maintenance during fed-batch culture.cho cell lines capable of high-level recombinant protein product biosynthesis during fed-batch culture are still generally obtained by intensive empirical screening of transfected cells rather than knowledge-guided cellular engineering. in this study, we investigate how cho cell lines create and maintain cellular biosynthetic capacity during fed-batch culture to achieve the optimal combination of rapid exponential proliferation and extended maintenance of high cell biomass concentration. we perf ...201729080362
identification of a potent mar element from the human genome and assessment of its activity in stably transfected cho cells.low-level and unstable transgene expression are common issues using the cho cell expression system. matrix attachment regions (mars) enhance transgene expression levels, but additional research is needed to improve their function and to determine their mechanism of action. mar-6 from cho chromosomes actively mediates high and consistent gene expression. in this study, we compared the effects of two new mars and mar-6 on transgene expression in recombinant cho cells and found one potent mar eleme ...201829077269
cho-omics review: the impact of current and emerging technologies on chinese hamster ovary based bioproduction.cho cells are the most prevalent platform for modern bio-therapeutic production. currently, there are several cho cell lines used in bioproduction with distinct characteristics and unique genotypes and phenotypes. these differences limit advances in productivity and quality that can be achieved by the most common approaches to bioprocess optimization and cell line engineering. incorporating omics-based approaches into current bioproduction processes will complement traditional methodologies to m ...201729072373
nanoliposomes for safe and efficient therapeutic mrna delivery: a step toward nanotheranostics in inflammatory and cardiovascular diseases as well as cancer.rationale: genetic therapy using modified mrna for specific therapeutic protein expression for disease treatment and vaccination represents a new field of therapeutic and diagnostic medicine. non-viral vectors transfection using biocompatible nanoliposomes enables safe and efficient delivery of therapeutic mrna. objective: generation of non-toxic, cell-compatible cationic nanoliposomes as nanotheranostic agents to successfully deliver therapeutic mrna. methods and results: cationic nanoliposomes ...201729071184
a possible link between kcnq2- and stxbp1-related encephalopathies: stxbp1 reduces the inhibitory impact of syntaxin-1a on m current.kv7 channels mediate the voltage-gated m-type potassium current. reduction of m current due to kcnq2 mutations causes early onset epileptic encephalopathies (eoees). mutations in stxbp1 encoding the syntaxin binding protein 1 can produce a phenotype similar to that of kcnq2 mutations, suggesting a possible link between stxbp1 and kv7 channels. these channels are known to be modulated by syntaxin-1a (syn-1a) that binds to the c-terminal domain of the kv7.2 subunit and strongly inhibits m current. ...201729067685
regulatory role of mir-18a to ccn2 by tgf-β1 signaling pathway in pulmonary injury induced by nano-sio2.this research is designed to investigate the regulatory effect of mir-18a to the target gene connective tissue growth factor (ctgf, or ccn2), by participating in tgf-β1 signaling pathway and explore the pathogenic mechanism of mir-18a in pulmonary injury induced by nano-sio2 based on our early study. mir-18a and expression of tgf-β1 in chinese hamster lung (chl) fibroblasts cells stimulated by supernatants of nr8383 cells exposed to 40 μg/ml nano-sio2 for 24 h demonstrated 1.58 ± 0.22-fold and 1 ...201829067610
z-505 hydrochloride ameliorates chemotherapy-induced anorexia in rodents via activation of the ghrelin receptor, ghsr1a.despite its therapeutic advantages, chemotherapy with anti-cancer drugs can cause adverse effects, including anorexia and weight loss. although most patients with cancer suffer from anorexia during chemotherapy, resulting in the need to suspend or cease treatment and thereby worsening prognosis, treatment options for anorexia remain limited. ghrelin is an orexigenic hormone that has been proposed to prevent anorexia. to investigate the potential of ghrelin receptor agonists, synthetic small-mole ...201829066414
multimodal chromatography for purification of biotherapeutics - a review.process chromatography forms the core of purification of biotherapeutics. the unparalleled selectivity that it offers over other alternatives combined with the considerable robustness and scalability make it the unit operation of choice in downstream processing. it is typical to have three to five chromatography steps in a purification process for a biotherapeutic. generally, these steps offer different modes of separation such as ion-exchange, reversed phase, size exclusion, and hydrophobic int ...201729065828
ca2+ -dependent down-regulation of human histamine h1 receptors in chinese hamster ovary cells.gq/11 protein-coupled human histamine h1 receptors in chinese hamster ovary cells stimulated with histamine undergo clathrin-dependent endocytosis followed by proteasome/lysosome-mediated down-regulation. in this study, we evaluated the effects of a sustained increase in intracellular ca2+ concentrations induced by a receptor-bypassed stimulation with ionomycin, a ca2+ ionophore, on the endocytosis and down-regulation of h1 receptors in chinese hamster ovary cells. all cellular and cell-surface ...201829063596
potentiation and block of asic1a by memantine.acid-sensing ion channels (asics) are modulated by various classes of ligands, including the recently described hydrophobic monoamines, which inhibit and potentiate asics in a subunit-specific manner. in particular, memantine inhibits asic1a and potentiates asic2a homomers. the aim of the present work was to characterize action mechanism of memantine on recombinant asic1a expressed in cho (chinese hamster ovary) cells. we have demonstrated that effect of memantine on asic1a strongly depends on m ...201729058095
hib antibody responses in infants following diphtheria, tetanus, acellular pertussis, and conjugated haemophilus influenzae type b (hib) combination vaccines with decreasing amounts of tetanus toxoid.while combination vaccines have contributed to improved vaccine uptake rates in children, studies have documented varied immunogenicity to specific vaccine components. we studied whether varying the amount of tetanus toxoid (tt) in a dtap and hib combination vaccine would result in immunogenicity comparable with separate, concurrent administration.201729054729
wavelet imaging on multiple scales (wims) reveals focal adhesion distributions, dynamics and coupling between actomyosin bundle stability.we introduce and use wavelet imaging on multiple scales (wims) as an improvement to fluorescence correlation spectroscopy to measure physical processes and features that occur across multiple length scales. in this study, wavelet transforms of cell images are used to characterize molecular dynamics at the cellular and subcellular levels (i.e. focal adhesions). we show the usefulness of the technique by applying wims to an image time series of a migrating osteosarcoma cell expressing fluorescentl ...201729049414
an investigation of methyl tert‑butyl ether‑induced cytotoxicity and protein profile in chinese hamster ovary cells.methyl tert-butyl ether (mtbe) is widely used as an oxygenating agent in gasoline to reduce harmful emissions. however, previous studies have demonstrated that mtbe is a cytotoxic substance that has harmful effects in vivo and in vitro. although remarkable progress has been made in elucidating the mechanisms underlying the mtbe‑induced reproductive toxicological effect in different cell lines, the precise mechanisms remain far from understood. the present study aimed to evaluate whether mammalia ...201729039499
construction and expression of vectors encoding biologically active rodent gonadotropins.the gonadotropins, luteinizing hormone (lh) and follicle-stimulating hormone (fsh), are important hormones in vertebrate reproduction. the isolation of gonadotropins from the pituitary gland is sub-optimal, as the cross-contamination of one hormone with another is common and often results in the variation in the measured activity of lh and fsh. the production of recombinant hormones is, therefore, a viable approach to solve this problem. this study aimed to express recombinant rat, mouse, and ma ...201729033405
types of cell death and apoptotic stages in chinese hamster ovary cells distinguished by raman spectroscopy.cell death is the ultimate cause of productivity loss in bioreactors that are used to produce therapeutic proteins. we investigated the ability of raman spectroscopy to detect the onset and types of cell death for chinese hamster ovary (cho) cells-the most widely used cell type for therapeutic protein production. raman spectroscopy was used to compare apoptotic, necrotic, autophagic, and control cho cells. several specific nucleic acid-, protein-, and lipid-associated marker bands within the 650 ...201829030978
kinetic characterization of bile salt transport by human ntcp (slc10a1).the transport of bile acids facilitated by ntcp is an important factor in establishing bile flow. in this study, we examine the kinetics associated with human ntcp-dependent transport of two quantitatively important bile acids comprising the human bile acid pool, chenodeoxycholic acid and glycine-chenodeoxycholate, and secondary bile salt, 3-sulfo-glycolithocholate of potential toxicological significance. the study employed human ntcp overexpressing chinese hamster ovary cells and results compar ...201829024779
proline-rich chaperones are compared computationally and experimentally for their abilities to facilitate recombinant butyrylcholinesterase tetramerization in cho cells.human butyrylcholinesterase (bche), predominantly tetramers with a residence time of days, offers the potential to scavenge organophosphorus pesticides and chemical warfare agents. efficient assembly of human bche into tetramers requires an association with proline-rich peptide chaperones. in this study, the incorporation of different proline-rich peptide chaperones into bche is investigated computationally and experimentally. first, the authors applied molecular dynamic (md) simulations to inte ...201729024569
evaluating the efficiency of chef and cmv promoter with ires and furin/2a linker sequences for monoclonal antibody expression in cho cells.in recent years, monoclonal antibodies (mabs) have been developed as powerful therapeutic and diagnostic agents and chinese hamster ovary (cho) cells have emerged as the dominant host for the recombinant expression of these proteins. a critical step in recombinant expression is the utilization of strong promoters, such as the chinese hamster elongation factor-1α (chef-1) promoter. to compare the strengths of chef with cytomegalovirus (cmv) promoter for mab expression in cho cells, four bicistron ...201729023479
parp inhibition by flavonoids induced selective cell killing to brca2-deficient cells.high consumption of dietary flavonoids might contribute to a reduction of cancer risks. quercetin and its glycosides have parp inhibitory effects and can induce selective cytotoxicity in brca2-deficient cells by synthetic lethality. we hypothesized that common flavonoids in diet naringenin, hesperetin and their glycosides have a similar structure to quercetin, which might have comparable parp inhibitory effects, and can induce selective cytotoxicity in brca2-deficient cells. we utilized chinese ...201729023372
serological and molecular investigation of 2117-like vesiviruses in cats.vesivirus 2117 was first discovered as a contaminant in chinese hamster ovary (cho) cell cultures used for human drug production. similar vesiviruses (vevs) have been detected recently in dogs. in order to address the hypothesis that cats may also be exposed to 2117-like vevs, in this study, we screened 236 feline sera using an enzyme-linked immunosorbent assay (elisa) based on a recombinant vp1 protein from the canine vev bari/212/07/ita. igg antibodies against the 2117-like vev were detected i ...201829022118
development of bioassay system for evaluation of materials for personal protective equipment (ppe) against toxic effects of ionizing radiations.health effects caused by ionizing radiations raise considerable concern among general public and radiation workers. to estimate ability of personal protective equipment (ppe) materials that reduce toxic effects of ionizing radiations, we developed an experimental bioassay system using chinese hamster v79 cells. the system developed here distinguished the biological effectiveness of x-ray that was significantly affected by elements composed of shielding materials. survival of the cells exposed to ...201729021414
manufacturing history of etanercept (enbrel®): consistency of product quality through major process revisions.etanercept (etn) (enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (tnf), a proinflammatory cytokine. etn is synthesized in chinese hamster ovary cells by recombinant dna technology as a fusion protein, with a fully human tnfrii ectodomain linked to the fc portion of human igg1. successful manufacture of biologics, such as etn, requires sophisticated process and product understanding, as well as meticulous control of operations to maintain product con ...201829020515
two-dimensional gel electrophoresis and 2d-dige.two-dimensional polyacrylamide gel electrophoresis (2d-page) continues to be one of the most versatile and widely used techniques to study the proteome of a biological system. in particular, a modified version of 2d-page, two-dimensional difference gel electrophoresis (2d-dige), which uses differential labeling of protein samples with up to three fluorescent tags, offers greater sensitivity and reproducibility over conventional 2d-page gels for differential quantitative analysis of protein expre ...201829019120
mutations causing acrodysostosis-2 facilitate activation of phosphodiesterase 4d3.type 2 acrodysostosis (acrdys2), a rare developmental skeletal dysplasia characterized by short stature, severe brachydactyly and facial dysostosis, is caused by mutations in the phosphodiesterase (pde) 4d (pde4d) gene. several arguments suggest that the mutations should result in inappropriately increased pde4d activity, however, no direct evidence supporting this hypothesis has been presented, and the functional consequences of the mutations remain unclear. we evaluated the impact of four diff ...201729016851
comparative assessment on the expression level of recombinant human follicle-stimulating hormone (fsh) in serum-containing versus protein-free culture media.production of recombinant pharmaceutical proteins has made a great contribution to modern biotechnology. at present, quick advances in protein expression lead to the enhancement of product quantity and quality as well as reduction in timescale processing. in the current study, we assessed the expression level of recombinant human follicle-stimulating hormone (rhfsh) in adherent and suspension chinese hamster ovary (cho) cell lines by cultivation in serum-containing and chemically defined, protei ...201728993982
equivalency of the quality of sublethal lesions after photons and high-linear energy transfer ion beams.the quality of the sublethal damage (sld) after irradiation with high-linear energy transfer (let) ion beams was investigated with low-let photons. chinese hamster v79 cells and human squamous carcinoma sas cells were first exposed to a priming dose of different ion beams at different lets at the heavy ion medical accelerator in the chiba facility. the cells were kept at room temperature and then exposed to a secondary test dose of x-rays. based on the repair kinetics study, the surviving fracti ...201728992250
dcpp1 is the mouse ortholog of human pauf that possesses functional analogy in pancreatic cancer.pancreatic adenocarcinoma upregulated factor (pauf) overexpressed in pancreatic ductal adenocarcinoma (pdac) plays a major role in tumor progression and metastasis by autocrine and paracrine manners. however, underlying molecular mechanism of pauf functioning in pancreatic cancer are not fully understood yet. the objective of this study was to evaluate the potential of demilune cell and parotid protein 1 (dcpp1) as a putative mouse ortholog of human pauf by sequence alignment and functional stud ...201728988106
mir-catch identifies biologically active mirna regulators of the pro-survival gene xiap, in chinese hamster ovary cells.genetic engineering of mammalian cells is of interest as a means to boost bio-therapeutic protein yield. x-linked inhibitor of apoptosis (xiap) overexpression has previously been shown to enhance cho cell growth and prolong culture longevity while additionally boosting productivity. the authors confirmed this across a range of recombinant products (seap, epo, and igg). however, stable overexpression of an engineering transgene competes for the cells translational machinery potentially compromisi ...201728976632
licochalcone a induces morphological and biochemical alterations in schistosoma mansoni adult worms.this paper is the first report on the in vitro effects of licochalcone a, a chalcone isolated from glycyrrhiza inflate batalin (leguminosae), on schistosoma mansoni adult worms. in vitro, licochalcone a afforded lethal concentrations for 50% of parasites (lc50) of 9.12±1.1 and 9.52±0.9μm against female and male adult worms, respectively, at 24h. additionally, the compound reduced the total number of s. mansoni eggs and affected the development of eggs produced by s. mansoni adult worms. together ...201728965009
optimization of a ph-shift control strategy for producing monoclonal antibodies in chinese hamster ovary cell cultures using a ph-dependent dynamic model.to optimize monoclonal antibody (mab) production in chinese hamster ovary cell cultures, culture ph should be temporally controlled with high resolution. in this study, we propose a new ph-dependent dynamic model represented by simultaneous differential equations including a minimum of six system component, depending on ph value. all kinetic parameters in the dynamic model were estimated using an evolutionary numerical optimization (real-coded genetic algorithm) method based on experimental time ...201728964661
feline vaccine-associated sarcomagenesis: is there an inflammation-independent role for aluminium?aluminium has been found in feline vaccine-associated sarcomas. in this study, we investigated the potential for aluminium to contribute directly to tumourigenesis. our results indicated that an aluminium hydroxide adjuvant preparation was cytotoxic and mutagenic in human-chinese hamster ovary (cho) hybrid cells in vitro. moreover, cho cells deficient in dna double strand break (dsb), but not single-strand break (ssb), repair, were particularly sensitive to aluminium exposure compared with repai ...201728960714
genotoxicity evaluation of alpha-linolenic acid-diacylglycerol oil.the alpha-linolenic acid (ala)-diacylglycerol (dag) oil is an edible oil enriched with dag (>80%) and ala (>50%). although dag oil, which mainly consists of oleic and linoleic acids has no genotoxic concerns, the fatty acid composition could affect the chemical property of dag. therefore, the purpose of this study was to evaluate the genotoxicity of ala-dag oil using standard genotoxicity tests in accordance with the oecd guidelines. ala-dag oil showed negative results in the bacterial reverse m ...201628959597
assessing and resolving model misspecifications in metabolic flux analysis.metabolic flux analysis (mfa) is an indispensable tool in metabolic engineering. the simplest variant of mfa relies on an overdetermined stoichiometric model of the cell's metabolism under the pseudo-steady state assumption to evaluate the intracellular flux distribution. despite its long history, the issue of model error in overdetermined mfa, particularly misspecifications of the stoichiometric matrix, has not received much attention. we evaluated the performance of statistical tests from line ...201728952528
metabolic characterization of a cho cell size increase phase in fed-batch cultures.normally, the growth profile of a cho cell fed-batch process can be divided into two main phases based on changes in cell concentration, being an exponential growth phase and a stationary (non-growth) phase. in this study, an additional phase is observed during which the cell division comes to a halt but the cell growth continues in the form of an increase in cell size. the cell size increase (si) phase occurs between the exponential proliferation phase (also called the number increase or ni pha ...201728951949
13c metabolic flux analysis identifies limitations to increasing specific productivity in fed-batch and perfusion.industrial cell culture requires substantial energy to generate protein. the protein generated is not only the product of interest (igg in this case), but also the protein associated with biomass. here, 13c-metabolic flux analysis (13c-mfa) was utilized to compare the stationary phase of a fed-batch process to a perfusion process producing the same product by the same clone. the fed-batch process achieved significantly higher specific productivity, approximately 60% greater than the perfusion pr ...201728951188
evaluation of genotoxicity and subchronic toxicity of the standardized leaves infusion extract of copaifera malmei harms in experimental models.copaifera malmei harms (fabaceae), known mainly as óleo-mirim, is a native and endemic plant found in the states of mato grosso and goiás of brazil. the plant's leaves infusion is popularly used by riverine communities of the northern araguaia microregion, mato grosso, brazil, for the treatment of gastric ulcers and inflammatory diseases of the respiratory tract. the gastric antiulcer activity of the standardized leaves infusion extract of copaifera malmei (siecm) in rodents has been reported. t ...201828943446
duodenal cytochrome b (cybrd1) ferric reductase functional studies in cells.dietary non-heme ferric iron is reduced by the ferric reductase enzyme, duodenal cytochrome b (dcytb), before absorption by the divalent metal transporter 1 (dmt1). a single nucleotide polymorphism (snp rs10455 mutant) that is located in the last exon of the dcytb gene was reported in c282y haemochromatosis hfe subjects. the present work therefore investigated the phenotype of this mutant dcytb in chinese hamster ovary (cho) cells. these cultured cells were transfected with either wild type (wt) ...201728937159
cell-free synthesis of functional antibodies using a coupled in vitro transcription-translation system based on cho cell lysates.antibodies are indispensable tools for basic research as well as diagnostic and therapeutic applications. consequently, the development of alternative manufacturing strategies which circumvent the hurdles connected to conventional antibody production technologies is of enormous interest. to address this issue, we demonstrate the synthesis of complex antibody formats, in particular immunoglobulin g (igg) and single-chain variable fragment fc fusion (scfv-fc), in a microsome-containing cell-free s ...201728931913
combinatorial genome and protein engineering yields monoclonal antibodies with hypergalactosylation from cho cells.one of the key quality attributes of monoclonal antibodies is the glycan pattern and distribution. two terminal galactose residues typically represent a small fraction of the total glycans from antibodies. however, antibodies with defined glycosylation properties including enhanced galactosylation have been shown to exhibit altered properties for these important biomedical modalities. in this study, the disruption of two α-2,3 sialyltransferases (st3gal4 and st3gal6) from chinese hamster ovary ( ...201728926673
methylglyoxal attenuates insulin signaling and downregulates the enzymes involved in cholesterol biosynthesis.methylglyoxal (mg) is a highly reactive dicarbonyl known to be elevated under the hyperglycemic conditions of diabetes and is implicated in the development of diabetic complications. therefore, the current study investigates the role of mg in exacerbating insulin resistance at the insulin signaling level, as well as its effect on the global proteomic level. by using insulin sensitive rat muscle cells (l6) and chinese hamster ovary (cho) cells stably expressing the insulin receptor (ir) and a glu ...201728926063
high frequency electroporation efficiency is under control of membrane capacitive charging and voltage potential relaxation.the study presents the proof of concept for a possibility to achieve a better electroporation in the mhz pulse repetition frequency (prf) region compared to the conventional low frequency protocols. the 200ns×10 pulses bursts of 10-14kv/cm have been used to permeabilize chinese hamster ovary (cho) cells in a wide range (1hz-1mhz) of prf. the permeabilization efficiency was evaluated using fluorescent dye assay (propidium iodide) and flow cytometry. it was determined that a threshold prf exists w ...201828922628
exploring cellular behavior under transient gene expression and its impact on mab productivity and fc-glycosylation.transient gene expression (tge) is a methodology employed in bioprocessing for the fast provision of recombinant protein material. mild hypothermia is often introduced to overcome the low yield typically achieved with tge and improve specific protein productivity. it is therefore of interest to examine the impact of mild hypothermic temperatures on both the yield and quality of transiently expressed proteins and the relationship to changes in cellular processes and metabolism. in this study, we ...201828921534
karyotype variation of cho host cell lines over time in culture characterized by chromosome counting and chromosome painting.genomic rearrangements are a common phenomenon in rapidly growing cell lines such as chinese hamster ovary (cho) cells, a feature that in the context of production of biologics may lead to cell line and product instability. few methods exist to assess such genome wide instability. here, we use the population distribution of chromosome numbers per cell as well as chromosome painting to quantify the karyotypic variation in several cho host cell lines. cho-s, cho-k1 8 mm glutamine, and cho-k1 cells ...201828921524
fed-batch cho cell culture for lab-scale antibody production.fed-batch culture is the most commonly used upstream process in industry today for recombinant monoclonal antibody production using chinese hamster ovary (cho) cells. developing and optimizing this process in the lab is crucial for establishing process knowledge, which enables rapid and predictable tech-transfer to manufacturing scale. in this chapter, we describe stepwise how to carry out fed-batch cho cell culture for lab-scale antibody production.201828921435
evaluation of genotoxicity and subchronic toxicity of standardized rose hip extract.rose hip is the fruit of the rose plant, which is widely used in food, cosmetics and as a traditional medicine. therefore, rose hip is considered safe and has a sufficient history of consumption as food. however, few studies have reported on the safety of rose hip extracts in toxicological analyses. thus, to evaluate the safety of rosehip polyphenol mj (rhpmj), an aqueous ethanol extract standardized with the trans-tiliroside content, we performed genotoxicity and 90-day repeated oral dose toxic ...201728920463
adipokinetic hormone receptor gene identification and its role in triacylglycerol mobilization and sexual behavior in the oriental fruit fly (bactrocera dorsalis).energy homeostasis requires continuous compensation for fluctuations in energy expenditure and availability of food resources. in insects, energy mobilization is under control of the adipokinetic hormone (akh) where it is regulating the nutritional status by supporting the mobilization of lipids. in this study, we characterized the gene coding for the akh receptor (akhr) and investigated its function in the oriental fruit fly (bactrocera dorsalis) that is economically one of the most important p ...201728919559
refractive index imaging of cells with variable-angle near-total internal reflection (tir) microscopy.the refractive index in the interior of single cells affects the evanescent field depth in quantitative studies using total internal reflection (tir) fluorescence, but often that index is not well known. we here present method to measure and spatially map the absolute index of refraction in a microscopic sample, by imaging a collimated light beam reflected from the substrate/buffer/cell interference at variable angles of incidence. above the tir critical angle (which is a strong function of refr ...201728918767
high-yield production of "difficult-to-express" proteins in a continuous exchange cell-free system based on cho cell lysates.cell-free protein synthesis (cfps) represents a promising technology for efficient protein production targeting especially so called "difficult-to-express" proteins whose synthesis is challenging in conventional in vivo protein production platforms. chinese hamster ovary (cho) cells are one of the most prominent and safety approved cell lines for industrial protein production. in this study we demonstrated the ability to produce high yields of various protein types including membrane proteins an ...201728916746
costunolide induces micronuclei formation, chromosomal aberrations, cytostasis, and mitochondrial-mediated apoptosis in chinese hamster ovary cells.costunolide (ce) is a sesquiterpene lactone well-known for its antihepatotoxic, antiulcer, and anticancer activities. the present study focused on the evaluation of the cytogenetic toxicity and cellular death-inducing potential of ce in cho cells, an epithelial cell line derived from normal ovary cells of chinese hamster. the cytotoxic effect denoting mtt assay has shown an ic50 value of 7.56 μm ce, where 50% proliferation inhibition occurs. the oxidative stress caused by ce was confirmed based ...201728914393
delayed effects of accelerated heavy ions on the induction of hprt mutations in v79 hamster cells.fundamental research on the harmful effects of ionizing radiation on living cells continues to be of great interest. recently, priority has been given to the study of high-charge and high-energy (hze) ions that comprise a substantial part of the galactic cosmic ray (gcr) spectra that would be encountered during long-term space flights. moreover, predictions of the delayed genetic effects of high linear energy transfer (let) exposure is becoming more important as heavy ion therapy use is increasi ...201728910671
teaching an old drug new tricks: agonism, antagonism, and biased signaling of pilocarpine through m3 muscarinic acetylcholine receptor.pilocarpine is a prototypical drug used to treat glaucoma and dry mouth and is classified as either a full or partial muscarinic agonist. here, we report several unexpected results pertaining to its interaction with muscarinic m3 receptor (m3r). we found that pilocarpine was 1000 times less potent in stimulating mouse-eye pupil constriction than muscarinic agonists oxotremorin-m (oxo-m) or carbachol (cch), although all three ligands have similar kd values for m3r. in contrast to cch or oxo-m, pi ...201728893976
brca2 protects mammalian cells from heat shock.heat shock induces dna double-strand breaks (dsbs) in mammalian cells. mammalian cells are capable of repairing dsbs by utilising the homologous recombination (hr) pathway. breast cancer susceptibility gene 2 (brca2) is known to regulate the hr pathway. here, we investigate the role of brca2 in repairing dna damage induced by heat shock.201728891354
sequential screening by clonepix fl and intracellular staining facilitate isolation of high producer cell lines for monoclonal antibody manufacturing.screening and characterization of cell lines for stable production are critical tasks in identifying suitable recombinant cell lines for the manufacture of protein therapeutics. to aid this essential function we have developed a methodology for the selection of antibody expressing cells using fluorescence based clonepix fl colony isolation and flow cytometry analysis following intracellular staining for immunoglobulin g (igg). our data show that characterization of cells by flow cytometry early ...201728890364
single-step purification of recombinant gaussia luciferase from serum-containing culture medium of mammalian cells.a dihydrofolate reductase-deficient chinese hamster ovary (cho-k1/dhfr-) cell line stably expressing gaussia luciferase with a histidine-tag sequence at the carboxyl terminus (glase-his) was established. recombinant glase-his was purified from serum-containing culture medium by single-step ni-chelate column chromatography in the presence of 2 m nacl and 0.01% tween 20. the protein yield of glase-his with over 95% purity was 0.5 mg from 0.9 l of the cultured medium. the enzymatic properties of pu ...201828888757
effects of ph, conductivity, host cell protein, and dna size distribution on dna clearance in anion exchange chromatography media.flowthrough anion exchange chromatography is commonly used as a polishing step in downstream processing of monoclonal antibodies and other therapeutic proteins to remove process-related impurities and contaminants such as host cell dna, host cell proteins, endotoxin, and viruses. dna with a wide range of molecular weight distributions derived from chinese hamster ovary cells was used to advance the understanding of dna binding behavior in selected anion exchange media using the resin (toyopearl ...201728884511
glycyrrhizic acid increases glucagon like peptide-1 secretion via tgr5 activation in type 1-like diabetic rats.glycyrrhizic acid (ga) is belonged to triterpenoid saponin that is contained in the root of licorice and is known to affect metabolic regulation. recently, glucagon like peptide-1 (glp-1) has widely been applied in diabetes therapeutics. however, the role of glp-1 in ga-induced anti-diabetic effects is still unknown. therefore, we are interested in understanding the association of glp-1 with ga-induced effects. in type 1-like diabetic rats induced by streptozotocin (stz-treated rats), ga increas ...201728881290
ecdysis triggering hormone signaling (eth/ethr-a) is required for the larva-larva ecdysis in bactrocera dorsalis (diptera: tephritidae).insects must undergo ecdysis for successful development and growth, and the ecdysis triggering hormone (eth), released by the inka cells, is a master hormone in this process. in this study, we determined the sequence of the eth precursor and receptors in an agriculturally important pest insect, the oriental fruit fly bactrocera dorsalis (hendel). we identified two functionally distinct splice receptor isoforms: bdeth-r-a and bdeth-r-b, and when expressed in chinese hamster ovary (cho-wta11) cell ...201728878684
lessons from the hamster: cricetulus griseus tissue and cho cell line proteome comparison.chinese hamster ovary cells represent the dominant host for therapeutic recombinant protein production. however, few large-scale data sets have been generated to characterize this host organism and derived cho cell lines at the proteomics level. consequently, an extensive label-free quantitative proteomics analysis of two cell lines (cho-s and cho dg44) and two chinese hamster tissues (liver and ovary) was used to identify a total of 11 801 unique proteins containing at least two unique peptides ...201728876938
impact of different promoters, promoter mutation, and an enhancer on recombinant protein expression in cho cells.in the present study, six commonly used promoters, including cytomegalovirus major immediate-early (cmv), the cmv enhancer fused to the chicken beta-actin promoter (cag), human elongation factor-1α (hef-1α), mouse cytomegalovirus (mouse cmv), chinese hamster elongation factor-1α (chef-1α), and phosphoglycerate kinase (pgk), a cmv promoter mutant and a cag enhancer, were evaluated to determine their effects on transgene expression and stability in transfected cho cells. the promoters and enhancer ...201728874794
preparation and biocompatibility of crosslinked poly(3-hydroxyundecenoate).a sticky polymer, poly(3-hydroxyundecenoate) (phu), was produced by pseudomonas oleovorans when nonanoate and undecenoate were used as carbon sources. crosslinked phu (cl-phu) was prepared by heating using benzoyl peroxide as a crosslinker. according to the degree of crosslinking in the polymer, three types of cl-phu were prepared: cl-phu50, cl-phu60 and cl-phu70. fourier transform-infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry results suggested that cro ...201828867233
growth rate changes in cho host cells are associated with karyotypic heterogeneity.chinese hamster ovary (cho) cell line instability and clonality issues can affect cell culture phenotypes such as cell growth, productivity, or product quality and remain challenges for biopharmaceutical manufacturing. while there have been efforts for characterizing cell line instability in cho production cell lines, a pre-existing level of cell line instability in cho host cells has not been determined. in this study, cell line instability and chromosomal heterogeneity of the host, cho-duk cel ...201728865132
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