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using a dihydrofolate reductase-based strategy for producing the biosimilar version of pertuzumab in cho-s cells.targeted therapy using monoclonal antibodies (mabs) against epidermal growth factor receptor-2 (erbb2) has been utilized for the treatment of breast cancer, recently. pertuzumab, one of the anti-erbb2 mabs, was approved by fda in 2012 for the treatment of metastatic breast cancer. the aim of this study was to produce biosimilar version of pertuzumab in chinese hamster ovary (cho)-s cell line, and compare its erbb2-binding and biological activities, with commercial drug, perjeta. to this end, a d ...201829437532
magnetic field direction differentially impacts the growth of different cell types.magnetic resonance imaging (mri) machines have horizontal or upright static magnetic field (smf) of 0.1-3 t (tesla) at sites of patients and operators, but the biological effects of these smfs still remain elusive. we examined 12 different cell lines, including 5 human solid tumor cell lines, 2 human leukemia cell lines and 4 human non-cancer cell lines, as well as the chinese hamster ovary cell line. permanent magnets were used to provide 0.2-1 t smfs with different magnetic field directions. w ...201829621414
all-trans retinoic acid in combination with sodium butyrate enhances specific monoclonal antibody productivity in recombinant cho cell line.the effects of all-trans retinoic acid (ra) and sodium butyrate (nabu) on growth, viability and antibody production of two types of transfected chinese hamster ovary cell lines (cho-k1 and cho-s) were investigated using a batch mode cell culture. by adding 0.5 mm nabu in the cho-k1 cell culture, the cell specific productivity (qp) and antibody concentration increased by five- and threefold, respectively. the optimal concentration of ra was 100 nm which resulted in twofold increase in antibody pr ...201829619548
toxic hypf-n oligomers selectively bind the plasma membrane to impair cell adhesion capability.the deposition of fibrillar protein aggregates in human organs is the hallmark of several pathological states, including highly debilitating neurodegenerative disorders and systemic amyloidoses. it is widely accepted that small oligomers arising as intermediates in the aggregation process, released by fibrils, or growing in secondary nucleation steps are the cytotoxic entities in protein-misfolding diseases, notably neurodegenerative conditions. increasing evidence indicates that cytotoxicity is ...201829590593
combination of temperature shift and hydrolysate addition regulates anti-ige monoclonal antibody charge heterogeneity in chinese hamster ovary cell fed-batch culture.charge heterogeneity has been broadly studied as a critical quality attribute during monoclonal antibody (mab) production that may subsequently affect product stability and biopotency. however, the charge variation distribution is poorly controlled, so methods of more effective control need to be explored. in this study, the combined effects of temperature shift (37-34, 37-32, or 37-30 °c) and hydrolysate addition (0.100 g/l) to culture feed on the charge heterogeneity of anti-ige mab were inves ...201829589263
heterologous expression of three antigenic proteins from angiostrongylus cantonensis: es-7, lec-5, and 14-3-3 in mammalian cells.angiostrongylus cantonensis is a parasitic nematode and the main causative agent of human cerebral eosinophilic meningoencephalitis (eom). a definitive diagnosis of eom usually requires serologic or molecular analysis of the patient's clinical sample. currently, a 31 kda antigen is used in immunological tests for this purpose, however as a crude antigen preparation it may present cross-reactivity with other helminthic infections, especially echinococcosis. heterologous expression studies using p ...201829555232
chemical modification of protein a chromatography ligands with polyethylene glycol. ii: effects on resin robustness and process selectivity.we have proposed chemical modification of protein a (proa) chromatography ligands with polyethylene glycol (pegylation) as a strategy to increase the resin selectivity and robustness by providing the ligand with a steric repulsion barrier against non-specific binding. here, we report on robustness and selectivity benefits for repligen captiva primab resin with ligands modified with 5.2 kda and 21.5 kda peg chains, respectively. pegylation of proa ligands allowed the resin to retain a higher perc ...201829551237
development and validation of chemical features-based proton-coupled folate transporter/activity and reduced folate carrier/activity models (pharmacophores).all clinically used antifolates lack transport selectivity for tumors over normal cells resulting in dose-limiting toxicities. there is growing interest in developing novel tumor-targeted cytotoxic antifolates with selective transport into tumors over normal cells via the proton-coupled folate transporter (pcft) over the ubiquitously expressed reduced folate carrier (rfc). a lack of x-ray crystal structures or predictive models for pcft or rfc has hindered structure-aided drug design for pcft-se ...201829550744
co-amplification of ebna-1 and pylt through dhfr-mediated gene amplification for improving foreign protein production in transient gene expression in cho cells.despite the relatively low transfection efficiency and low specific foreign protein productivity (qp) of chinese hamster ovary (cho) cell-based transient gene expression (tge) systems, tge-based recombinant protein production technology predominantly employs cho cells for pre-clinical research and development purposes. to improve tge in cho cells, epstein-barr virus nuclear antigen-1 (ebna-1)/polyoma virus large t antigen (pylt)-co-amplified recombinant cho (rcho) cells stably expressing ebna-1 ...201829654557
in situ formation of injectable chitosan-gelatin hydrogels through double crosslinking for sustained intraocular drug delivery.rapid clearance and low ocular bioavailability are drawbacks of conventional ophthalmic eye drops. to increase the ocular drug resistance time and improve efficacy, an in situ forming and thermosensitive chitosan-gelatin hydrogel was developed. the feasibility of using this hydrogel as a topical eye drop formulation for sustained release of timolol maleate was evaluated. the flexible hydrogel that was co-crosslinked with β‑glycerophosphate disodium salt hydrate (β-gd) and genipin showed a fast g ...201829636124
purification of human erythropoietin by affinity chromatography using cyclic peptide ligands.prior work described the identification and characterization of erythropoietin-binding cyclic peptides slfflh, vvffvh, fsllhh and fsllsh (all of the form cyclo[(nα-ac)dap(a)-x1-x6-ae], wherein x1-x6 is the listed sequences). in this work, the peptide ligands were synthesized on toyopearl chromatographic resins and utilized for purifying recombinant human erythropoietin (rhuepo) from complex sources. elution buffer ph and composition were optimized to maximize the recovery of standard rhuepo from ...201829625371
assessment of genotoxic activity of oleoresins and leaves extracts of six copaifera species for prediction of potential human risks.copaifera species are used in folk medicine for a wide variety of pharmacological properties. this paper reports the cytotoxic and genotoxic analyses of oleoresins and leaves extracts of copaifera species: c. duckei, c. multijuga, c. paupera, c. pubiflora, c. reticulata and c. trapezifolia.201829625274
monoclonal antibody l1mab-13 detected human pd-l1 in lung cancers.programmed cell death ligand-1 (pd-l1) is a type i transmembrane glycoprotein expressed on antigen-presenting cells. it is also expressed in several tumor cells such as melanoma and lung cancer cells. a strong correlation has been reported between human pd-l1 (hpd-l1) expression in tumor cells and negative prognosis in cancer patients. here, a novel anti-hpd-l1 monoclonal antibody (mab) l1mab-13 (igg1, kappa) was produced using a cell-based immunization and screening (cbis) method. we investigat ...201829608408
multiple reaction monitoring targeted lc-ms analysis of potential cell death marker proteins for increased bioprocess control.the monitoring of protein biomarkers for the early prediction of cell stress and death is a valuable tool for process characterization and efficient biomanufacturing control. a representative set of six proteins, namely gpdh, prdx1, lgals1, cfl1, tagln2 and mdh, which were identified in a previous cho-k1 cell death model using discovery lc-mse was translated into a targeted liquid chromatography multiple reaction monitoring mass spectrometry (lc-mrm-ms) platform and verified. the universality of ...201829607450
mechanisms driving the lactate switch in chinese hamster ovary cells.the metabolism of chinese hamster ovary (cho) cells in a production environment has been extensively investigated. however, a key metabolic transition, the switch from lactate production to lactate consumption, remains enigmatic. though commonly observed in cho cultures, the mechanism(s) by which this metabolic shift is triggered is unknown. despite this, efforts to control the switch have emerged due to the association of lactate consumption with improved cell growth and productivity. this revi ...201829603726
an engineered complement factor h construct for treatment of c3 glomerulopathy.background c3 glomerulopathy (c3g) is associated with dysregulation of the alternative pathway of complement activation, and treatment options for c3g remain limited. complement factor h (fh) is a potent regulator of the alternative pathway and might offer a solution, but the mass and complexity of fh makes generation of full-length fh far from trivial. we previously generated a mini-fh construct, with fh short consensus repeats 1-5 linked to repeats 18-20 (fh1-5^18-20), that was effective in ex ...201829588430
identification of high affinity her2 binding antibodies using cho fab surface display.discovery of monoclonal antibodies is most commonly performed using phage or yeast display but mammalian cells are used for production because of the complex antibody structure, including the multiple disulfide bonds and glycosylation, required for function. as this transition between host organisms is often accompanied by impaired binding, folding or expression, development pipelines include laborious plate-based screening or engineering strategies to adapt an antibody to mammalian expression. ...201829566240
toxicological evaluation of 6'-sialyllactose (6'-sl) sodium salt.we performed a series of toxicity studies on the safety of 6'-sialyllactose (6'-sl) sodium salt as a food ingredient. 6'-sl sodium salt, up to a maximum dose of 5000 μg/plate, did not increase the number of revertant colonies in five strains of salmonella typhimurium in the presence or absence of s9 metabolic activation. a chromosomal aberration assay (using chinese hamster lung cells) found no clastogenic effects at any concentration of 6'-sl sodium salt in the presence or absence of s9 metabol ...201829555556
mild hypothermia upregulates myc and xbp1s expression and improves anti-tnfα production in cho cells.chinese hamster ovary (cho) cells are the most frequently used host for commercial production of therapeutic proteins. however, their low protein productivity in culture is the main hurdle to overcome. mild hypothermia has been established as an effective strategy to enhance protein specific productivity, although the causes of such improvement still remain unclear. the self-regulation of global transcriptional regulatory factors, such as myc and xbp1s, seems to be involved in increased the reco ...201829566086
inhibition of the α-subunit of phosphoinositide 3-kinase in heart increases late sodium current and is arrhythmogenic.although inhibition of phosphoinositide 3-kinase (pi3k) is an emerging strategy in cancer therapy, we and others have reported that this action can also contribute to drug-induced qt prolongation and arrhythmias by increasing cardiac late sodium current (inal). previous studies in mice implicate the pi3k-α isoform in arrhythmia susceptibility. here, we have determined the effects of new anticancer drugs targeting specific pi3k isoforms on inal and action potentials (aps) in mouse cardiomyocytes ...201829563327
human umbilical cord blood serum-derived α-secretase: functional testing in alzheimer's disease mouse models.alzheimer's disease (ad) is an age-related disorder that affects cognition. our previous studies showed that the neuroprotective fragment of amyloid procurer protein (app) metabolite, soluble appα (sappα), interferes with β-site app-cleaving enzyme 1 (bace1, β-secretase) cleavage and reduces amyloid-β (aβ) generation. in an attempt to identify approaches to restore sappα levels, we found that human cord blood serum (cbs) significantly promotes sappα production compared with adult blood serum (ab ...201829560732
process analytical technology for advanced process control in biologics manufacturing with the aid of macroscopic kinetic modeling.productivity improvements of mammalian cell culture in the production of recombinant proteins have been made by optimizing cell lines, media, and process operation. this led to enhanced titers and process robustness without increasing the cost of the upstream processing (usp); however, a downstream bottleneck remains. in terms of process control improvement, the process analytical technology (pat) initiative, initiated by the american food and drug administration (fda), aims to measure, analyze, ...201829547557
protein oxidative damage and redox imbalance induced by ionising radiation in cho cells.reactive oxygen species (ros) are important mediators of the cytotoxicity induced by the direct reaction of ionising radiation (ir) with all critical cellular components, such as proteins, lipids, and nucleic acids. the derived oxidative damage may propagate in exposed tissues in a dose- and spatiotemporal dependent manner to other cell compartments, affecting intracellular signalling, and cell fate. to understand how cell damage is induced, we studied the oxidative events occurring immediately ...201829546780
elucidating the impact of cho cell culture media on tryptophan oxidation of a monoclonal antibody through gene expression analyses.oxidation of monoclonal antibodies (mab) is a common chemical modification with potential impact on a therapeutic protein's activity and immunogenicity. in a previous study, it was found that tryptophan oxidation (trp-ox) levels of two mab produced in chinese hamster ovary (cho) cells were significantly lowered by modifying cell culture medium/feed. in this study, transcriptome analysis by rna-seq is applied to further elucidate the underlying mechanism of those changes in lowering the trp-ox le ...201829542860
evaluation of fluorescent dyes to measure protein aggregation within mammalian cell culture supernatants.a current challenge in bioprocessing is the ability to analyse critical quality attributes such as aggregation without prior purification. this study evaluated the use of fluorescent dyes (bis-ans, sypro orange, thioflavin t and proteostat) to characterise mab aggregates in chinese hamster ovary clarified cultures.201829540956
protein a affinity chromatography of chinese hamster ovary (cho) cell culture broths containing biopharmaceutical monoclonal antibody (mab): experiments and mechanistic transport, binding and equilibrium modeling.protein a-based affinity chromatography is a highly-efficient separation method to capture, purify and isolate biosimilar monoclonal antibodies (mab) - an important medical product of biopharmaceutical industrial manufacturing. it is considered the most expensive step in purification downstream operations; therefore, its performance optimization offers a great cost saving in the overall production expenditure. the biochemical mixture-separating specific interaction experiments with chinese hamst ...201829522957
glyco-mapper: a chinese hamster ovary (cho) genome-specific glycosylation prediction tool.glyco-mapper is a novel systems biology product quality prediction tool created using a new framework termed: discretized reaction network modeling using fuzzy parameters (dream-zyp). within glyco-mapper, users fix the nutrient feed composition and the glycosylation reaction fluxes to fit the model glycoform to the reference experimental glycoform, enabling cell-line specific glycoform predictions as a result of cell engineering strategies. glyco-mapper accurately predicts glycoforms associated ...201829522825
understanding biopharmaceutical production at single nucleotide resolution using ribosome footprint profiling.biopharmaceuticals such as monoclonal antibodies have revolutionised the treatment of a variety of diseases. the production of recombinant therapeutic proteins, however, remains expensive due to the manufacturing complexity of mammalian expression systems and the regulatory burden associated with administrating these medicines to patients in a safe and efficacious manner. in recent years, academic and industrial groups have begun to develop a greater understanding of the biology of host cell lin ...201829471208
smad4-independent activation of tgf-β signaling by muc1 in a human pancreatic cancer cell line.pancreatic ductal adenocarcinoma (pda) has a mortality rate that nearly matches its incidence rate. transforming growth factor beta (tgf-β) is a cytokine with a dual role in tumor development switching from a tumor suppressor to a tumor promoter. there is limited knowledge of how tgf-β function switches during tumorigenesis. mucin 1 (muc1) is an aberrantly glycosylated, membrane-bound, glycoprotein that is overexpressed in >80% of pda cases and is associated with poor prognosis. in pda, muc1 pro ...201829467938
a comparative study of using free radical generators in the testing of chosen oxidative stress parameters in the different types of cells.the aim of this study was to assess whether there are differences between the results of determining oxidative stress markers obtained from different origin cell lines after exposure to chemicals generating free radicals. the studies considered two markers of oxidative stress: the level of thiobarbituric acid reactive substances (tbars) and superoxide dismutase activity. the evaluation was performed in five cell lines: chinese hamster ovary (cho-9) cells, lung adenocarcinoma a549, macrophages ra ...201829519201
antibacterial effect of copaifera duckei dwyer oleoresin and its main diterpenes against oral pathogens and their cytotoxic effect.this study evaluates the antibacterial activity of the copaifera duckei dwyer oleoresin and two isolated compounds [eperu-8(20)-15,18-dioic acid and polyalthic acid] against bacteria involved in primary endodontic infections and dental caries and assesses the cytotoxic effect of these substances against a normal cell line. mic and mbc assays pointed out the most promising metabolites for further studies on bactericidal kinetics, antibiofilm activity, and synergistic antibacterial action. the ole ...201829515530
biogenesis of silver nanoparticles using leaf extract of indigofera hirsuta l. and their potential biomedical applications (3-in-1 system).the present study reports the biosynthesis of silver nanoparticles (ih-agnps) using aqueous leaf extract of indigofera hisruta l. the biosynthesized ih-agnps were found to be fcc crystals, 5-10 nm in size, spherical in shape and stable. the biosynthesized ih-agnps showed dose-dependant cytotoxicity against prostate cancer (pc3) (ic50 = 68.5 μg/ml), colon cancer (colo205) (ic50 = 85.2 μg/ml), and mouse melanoma (b16f10) (ic50 = 80.9 μg/ml). ih-agnps were found to be nontoxic towards normal cho (c ...201829513113
the combined effect of pdx1 overexpression and shh manipulation on the function of insulin-producing cells derived from adipose-tissue stem cells.pancreatic and duodenal homeobox 1 (pdx1) and sonic hedgehog (shh) are the key regulators of beta-cell function. in vitro experiments have shown that there is significant cooperation between pdx1 and shh with regard to the production and maintenance of insulin-producing cells (ipcs). in this study, the combined effect of pdx1 overexpression and shh manipulation on the function of adipose tissue-derived ipcs was determined. a eukaryotic expression vector (pdx1- pcdna3.1(+)) was constructed and tr ...201829511614
probing lactate metabolism variations in large-scale bioreactors.lactate metabolism variations are frequently encountered in mammalian cell culture processes, especially during process scale-up. in this study, we took a multipronged approach to investigate the impact of ph, pco2 , osmolality, base addition, and mixing conditions on the observed lactate variations in a chinese hamster ovary (cho) fed-batch process at 2,000 l scale. two cultivating methods, co2 -controlled and ph-controlled, were used to decouple the individual and synergistic effects from thos ...201829464875
the concept of hybrid molecules of tacrine and benzyl quinolone carboxylic acid (bqca) as multifunctional agents for alzheimer's disease.novel tacrine-benzyl quinolone carboxylic acid (tacrine-bqca) hybrids were designed based on multi-target directed ligands (mtlds) paradigm, synthesized and evaluated in vitro as inhibitors of human acetylcholinesterase (hache) and human butyrylcholinesterase (hbche). tacrine moiety is represented herein as 7-methoxytacrine, 6-chlorotacrine or unsubstituted tacrine forming three different families of seven members, i.e. 21 compounds in overall. introducing bqca, a positive modulator of m1 muscar ...201829533874
the protective effect of niacinamide on cho aa8 cell line against ultraviolet radiation in the context of main cytoskeletal proteins.niacinamide is a stable and water-soluble form of vitamin b3, a valuable and versatile cosmetic ingredient, which is well absorbed and tolerated by the skin. a large body of literature has reported on the antioxidant and cell repair properties of niacinamide. therefore, it has been shown to be useful in the protection of the skin against ultraviolet b (uvb) radiation and free radicals. despite numerous hypotheses on the mechanism of vitamin b3, its protective effects have not yet been fully eluc ...201829533537
glycoengineering of mammalian expression systems on a cellular level.mammalian expression systems such as chinese hamster ovary (cho), mouse myeloma (ns0), and human embryonic kidney (hek) cells serve a critical role in the biotechnology industry as the production host of choice for recombinant protein therapeutics. most of the recombinant biologics are glycoproteins that contain complex oligosaccharide or glycan attachments representing a principal component of product quality. both n-glycans and o-glycans are present in these mammalian cells, but the engineerin ...201829532110
antioxidant activity of ge-132, a synthetic organic germanium, on cultured mammalian cells.ge-132 is a synthetic organic germanium that is used as a dietary supplement. the antioxidant activity of ge-132 on cultured mammalian cells was investigated in this study. first, ge-132 cytotoxicity on mammalian cultured cells was determined by measuring lactate dehydrogenase (ldh) levels. ge-132 had no cytotoxic effect on three different cell lines. second, the cell proliferative effect of ge-132 was determined by measuring atp content of whole cells and counting them. ge-132 treatment of chin ...201829503400
effects of silver sulfide quantum dots coated with 2-mercaptopropionic acid on genotoxic and apoptotic pathways in vitro.quantum dots (qds) are highly promising nanomaterials in bioimaging system because of their bright fluorescence, broad uv excitation, narrow emission band, and high photostability. recently, there is a great activity on ag2s quantum dots for both imaging and drug/gene delivery due to the potential of having a better cytocompatability and near infrared luminescence. 2-mercaptopropionic acid (2 mp a)-coated silver sulfide (ag2s) qds were reported as the most luminescent, stable, anionic ag2s qds i ...201829958870
high cell density perfusion culture has a maintained exoproteome and metabolome.the optimization of bioprocesses for biopharmaceutical manufacturing by chinese hamster ovary (cho) cells can be a challenging endeavor and, today, heavily relies on empirical methods treating the bioreactor process and the cells as black boxes. multi-omics approaches have the potential to reveal otherwise unknown characteristics of these systems and identify culture parameters to more rationally optimize the cultivation process. here, the authors have applied both metabolomic and proteomic prof ...201829957873
photosensitization of chinese hamster v79 cells to photoactivated alpha-terthienyl involving membrane damage and oxidative stress.photosensitization of v79 chinese hamster lung fibroblasts was tested to investigate if the cells can fit the photoactive effect of alpha-terthienyl for safety application. using 15-min photoirradiation of a black light (320-400 nm, 40 w), alpha-terthienyl was significantly photoactivated and caused v79 cells to be shrinkage, detachment and necrosis. the photoactivated alpha-terthienyl played a concentration-dependent stress to decrease cell survival and to induce cell death with median inhibito ...201829957498
mechanisms of precipitate formation during the purification of an fc-fusion protein.protein precipitates that arise during bioprocessing can cause manufacturing challenges, but they can also aid in clearance of host-cell protein (hcp) and dna impurities. such precipitates differ from many protein precipitates that have been studied previously in their heterogeneous composition, particularly in the presence of high concentrations of the product protein. here, we characterize the precipitates that form after neutralization of protein a purified and viral-inactivated material of a ...201829896879
heterologous expression of ctp:phosphocholine cytidylyltransferase from plasmodium falciparum rescues chinese hamster ovary cells deficient in the kennedy phosphatidylcholine biosynthesis pathway.the plasmodial ctp:phosphocholine cytidylyltransferase (pfcct) is a promising antimalarial target, which can be inhibited to exploit the need for increased lipid biosynthesis during the erythrocytic life stage of plasmodium falciparum. notable structural and regulatory differences of plasmodial and mammalian ccts offer the possibility to develop species-specific inhibitors. the aim of this study was to use cho-mt58 cells expressing a temperature-sensitive mutant cct for the functional characteri ...201829895950
safety assessment of the cistanche tubulosa health food product memoregain®: genotoxicity and 28-day repeated dose toxicity test.the pharmacological effects of cistanches herba, known as "ginseng of the desert", have been extensively studied. in this study, we aimed to assess the genotoxic and oral toxic effects of the cistanche tubulosa health food product memoregain® using in vitro and in vivo tests. ames tests using five strains of salmonella typhimurium showed no signs of increased reverse mutation upon exposure to memoregain® up to a concentration of 5 mg/plate. exposure of chinese hamster ovary (cho-k1) cells to mem ...201829886232
optimization of a high-cell-density polyethylenimine transfection method for rapid protein production in cho-ebna1 cells.for pre-clinical evaluation of biotherapeutic candidates, protein production by transient gene expression (tge) in chinese hamster ovary (cho) cells offers important advantages, including the capability of rapidly and cost-effectively generating recombinant proteins that are highly similar to those produced in stable cho clones. we have established a novel cho clone (cho-3e7) expressing a form of the epstein-barr virus nuclear antigen-1 (ebna-1) with improved tge productivity relative to parenta ...201829886030
effective and efficient characterization of chinese hamster ovary production cell lines using automated intracellular staining and statistical modeling.mammalian cell line development is critical to bioproduct manufacturing. success requires selecting a line with desirable performance characteristics, including consistent expression throughout the proposed manufacturing window. given the genetic and phenotypic flux inherent to immortalized lines such as chinese hamster ovary cells, clonally-derived cell line characterization is vital. we describe here the development and implementation of a novel addition to our characterization approach to ens ...201829882242
application of microrna targeted 3'utrs to repress dhfr selection marker expression for development of recombinant antibody expressing cho cell pools.the dihydrofolate reductase (dhfr) system is used for the selection of recombinant chinese hamster ovary (cho) cell lines using the inhibitor methotrexate (mtx). during clonal selection, endogenous dhfr expression, and resistance to mtx allows the selection of cells expressing sufficient dhfr to survive. here, the authors describe a novel vector platform for the dhfr system, whereby addition of a synthetic 3'utr destabilizes dhfr expression. mirs ability to negatively regulate gene expression by ...201829981248
paxillin phosphorylation at serine 273 and its effects on rac, rho and adhesion dynamics.focal adhesions are protein complexes that anchor cells to the extracellular matrix. during migration, the growth and disassembly of these structures are spatiotemporally regulated, with new adhesions forming at the leading edge of the cell and mature adhesions disassembling at the rear. signalling proteins and structural cytoskeletal components tightly regulate adhesion dynamics. paxillin, an adaptor protein within adhesions, is one of these proteins. its phosphorylation at serine 273 (s273) is ...201829975690
mpo (myeloperoxidase) reduces endothelial glycocalyx thickness dependent on its cationic charge.objective- the leukocyte heme-enzyme mpo (myeloperoxidase) exerts proinflammatory effects on the vascular system primarily linked to its catalytic properties. recent studies have shown that mpo, depending on its cationic charge, mediates neutrophil recruitment and activation. here, we further investigated mpo's extracatalytic properties and its effect on endothelial glycocalyx (eg) integrity. approach and results- in vivo staining of murine cremaster muscle vessels with alcian blue 8gx provided ...201829903730
the binding of captopril to angiotensin i-converting enzyme triggers activation of signaling pathways.hypertension is a global health problem, and angiotensin i (ang i)-converting enzyme (ace) inhibitors are largely used to control this pathology. recently, it has been shown that ace can also act as a transducer signal molecule when its inhibitors or substrates bind to it. this new role of ace could contribute to understanding some of the effects not explained by its catalytic activity only. in this study, we investigated signaling pathway activation in chinese hamster ovary (cho) cells stably e ...201829874111
a gold nanoparticle bio-optical transponder to dynamically monitor intracellular ph.a ph-sensitive bio-optical transponder (ph-bot) capable of simultaneously reporting the timing of intracellular dna cargo release from a gold nanoparticle (aunp) and the evolving intracellular ph (ph i) during endosomal maturation is demonstrated. the ph-bot is designed with a triple-dye-labeled duplex dna appended to a 6.6 nm aunp, utilizing ph-responsive fluorescein paired with dylight405 as a surface energy transfer (set) coupled dye pair to ratiometrically report the ph at and after cargo re ...201829874043
lactoferrin prevents susceptibility of wehi 231 cells to anti-ig-induced cell death promoting cell differentiation.immature b cells are susceptible to apoptosis due to ligation of surface immunoglobulin receptors. the wehi 231 cell line represents a useful model to study the mode of action of factors preventing apoptosis. in this work we investigated the protective effects of multi-species lactoferrins in anti-mouse ig-induced wehi 231 cell death. bovine milk-derived lactoferrin (blf), recombinant human lactoferrin expressed in chinese hamster ovary cells - rhlf(cho) or in human endothelial kidney cells - rh ...201829871734
amp-activated protein kinase mediates the effect of leptin on avian autophagy in a tissue-specific manner.autophagy, a highly conserved intracellular self-digestion process, plays an integral role in maintaining cellular homeostasis. although emerging evidence indicate that the endocrine system regulates autophagy in mammals, there is still a scarcity of information on autophagy in avian (non-mammalian) species. here, we show that intracerebroventricular administration of leptin reduces feed intake, modulates the expression of feeding-related hypothalamic neuropeptides, activates leptin receptor and ...201829867578
crispr/cas9-multiplexed editing of chinese hamster ovary b4gal-t1, 2, 3, and 4 tailors n-glycan profiles of therapeutics and secreted host cell proteins.in production of recombinant proteins for biopharmaceuticals, n-glycosylation is often important for protein efficacy and patient safety. igg with agalactosylated (g0)-n-glycans can improve the activation of the lectin-binding complement system and be advantageous in the therapy of lupus and virus diseases. in this study, the authors aimed to engineer cho-s cells for the production of proteins with g0-n-glycans by targeting b4gal-t isoform genes with crispr/cas9. indel mutations in genes encodin ...201829862652
clonal variation in productivity and proteolytic clipping of an fc-fusion protein in cho cells: proteomic analysis suggests a role for defective protein folding and the upr.product degradation, such as clipping, is a common quality issue in the production of fc-fusion proteins from chinese hamster ovary (cho) cells. degradation of proteins is mainly due to the action of either intracellular or extracellular host cell proteases. this study was carried out to understand more fundamentally the intracellular events that may play a role in determining why cell lines from the same cell line development project can vary with regards to the extent of fc-fusion protein clip ...201829860056
luminescence from lanthanide(iii) ions bound to the glycocalyx of chinese hamster ovary cells.lanthanide(iii) ions bind to the glycocalyx of chinese hamster ovary (cho) cells and give rise to a unique luminescent fingerprint. following direct excitation of terbium(iii) and europium(iii) ions in the visible part of the spectrum, we are able to collect emission spectra pixel-by-pixel in images of cho cells. following data analysis that removes the background signal, the fine structure of the europium(iii) luminescence indicate that the lanthanide(iii) ions are bound to a single structure o ...201829939467
sonochemical synthesis of small boron oxide nanoparticles.the synthesis of small boron oxide nanoparticles (nps) is reported. a sonochemical approach in the presence of a capping agent was employed to produce approximately 4-5-nm-sized b2o3 nps, including the 10b isotopically enriched form. the morphology and composition of the nps were established using transmission electron microscopy and diffraction, respectively. x-ray photoelectron and fourier transform infrared spectroscopies provided information about surface functionalization of the b2o3 nps, w ...201829939022
functional comparison of high and low molecular weight basic fibroblast growth factors.acid-electrolyzed functional water (fw) is obtained through the electrolysis of sodium chloride solution. stimulation of the human fibroblastic cell line hela by fw led to the augmented secretion of basic fibroblast growth factor (bfgf). immunoprecipitation followed by western blot analysis revealed that both high and low molecular weight isoforms of bfgf were secreted in response to fw treatment. to explore intracellular bfgf localization, a cell fractionation assay was performed. despite the p ...201829923210
ultra-low carbon dioxide partial pressure improves the galactosylation of a monoclonal antibody produced in chinese hamster ovary cells in a bioreactor.to explore the influence of ultra-low carbon dioxide partial pressure (pco2) on the monoclonal antibody (mab) n-glycosylation profile in chinese hamster ovary (cho) cell culture.201829923054
a biotinylated and endoplasmic reticulum-targeted glutathione-responsive zinc(ii) phthalocyanine for targeted photodynamic therapy.a biotinylated glutathione (gsh)-responsive zinc(ii) phthalocyanine has been prepared and characterized. with a 2,4-dinitrobenzenesulfonyl moiety, its fluorescence emission and singlet oxygen generation were silenced in its intact state. upon exposure to high concentration of gsh, its photosensitizing properties were restored in phosphate buffered saline and inside tumor cells. it also showed preferential uptake on hepg2 human hepatocarcinoma cells (with higher biotin receptor expression) rather ...201829956487
automated single-cell analysis and isolation system: a paradigm shift in cell screening methods for bio-medicines.we have developed an automated robot that facilitates non-invasive isolation of a single cell with the most favorable properties from arrays containing >105 cells, thus allowing the establishment of new cell screening methods for bio-medicines. in this chapter, an outline of the proposed automated single-cell analysis and isolation system (hereafter called 'single-cell robot') is reviewed by comparison with a conventional fluorescence-activated cell sorter (facs). the single-cell robot could per ...201829943292
meta-analysis of publicly available chinese hamster ovary (cho) cell transcriptomic datasets for identifying engineering targets to enhance recombinant protein yields.transcriptomics has been extensively applied to the investigation of the cho cell platform for the production of recombinant biotherapeutic proteins to identify transcripts whose expression is regulated and correlated to (non)desirable cho cell attributes. however, there have been few attempts to analyze the findings across these studies to identify conserved changes and generic targets for cho cell platform engineering. here, the authors have undertaken a meta-analysis of cho cell transcriptomi ...201829917317
stable expression of infliximab in crispr/cas9-mediated bak1-deficient cho cells.to establish stable infliximab-expressing chinese hamster ovary (cho) cells with high tolerance to serum-free culture.201829915899
untangling the mechanism of 3-methyladenine in enhancing the specific productivity: transcriptome analysis of recombinant chinese hamster ovary cells treated with 3-methyladenine.3-methyladenine (3-ma) is a chemical additive that enhances the specific productivity (q p ) in recombinant chinese hamster ovary (rcho) cell lines. different from its widely known function of inhibiting autophagy, 3-ma has instead shown to increase autophagic flux in various rcho cell lines. thus, the mechanism by which 3-ma enhances the qp requires investigation. to evaluate the effect of 3-ma on transcriptome dynamics in rcho cells, rna-seq was performed with fc-fusion protein-producing rcho ...201829940077
igg responses to the plasmodium falciparum antigen var2csa in colombia are restricted to pregnancy and are not induced by exposure to plasmodium vivax.clinical immunity to malaria is associated with the acquisition of igg specific for members of the plasmodium falciparum erythrocyte membrane protein 1 (pfemp1) family of clonally variant antigens on the surface of infected erythrocytes (ies). the var2csa subtype of pfemp1 mediates ie binding in the placenta. var2csa-specific igg is normally acquired only after exposure to placental parasites. however, it was recently reported that men and children from colombia often have high levels of functio ...201829784859
cell propagation of cholera toxin cta adp-ribosylating factor by exosome mediated transfer.in this study, we report how the cholera toxin (ct) a subunit (cta), the enzyme moiety responsible for signaling alteration in host cells, enters the exosomal pathway, secretes extracellularly, transmits itself to a cell population. the first evidence for long-term transmission of ct's toxic effect via extracellular vesicles was obtained in chinese hamster ovary (cho) cells. to follow the ct intracellular route towards exosome secretion, we used a novel strategy for generating metabolically-labe ...201829783743
estimation of the radiation-induced dna double-strand breaks number by considering cell cycle and absorbed dose per cell nucleus.dna double-strand breaks (dsbs) are thought to be the main cause of cell death after irradiation. in this study, we estimated the probability distribution of the number of dsbs per cell nucleus by considering the dna amount in a cell nucleus (which depends on the cell cycle) and the statistical variation in the energy imparted to the cell nucleus by x-ray irradiation. the probability estimation of dsb induction was made following these procedures: (i) making use of the chinese hamster ovary (cho ...201829800455
generation of high expressing chinese hamster ovary cell pools using the leap-in transposon system.clonally derived cell lines (cdcl) from chinese hamster ovary (cho) host cell lines, remain the most popular method to manufacture therapeutic proteins. however, cho cell pools are increasingly being used as an alternate method to produce therapeutic proteins for preclinical drug development in an effort to shorten the time required for new drug development. it is essential that these cho pools exhibit the desired attributes of cho cdcls such as high protein titers and consistent product quality ...201829797786
inactivation of deubiquitinase cyld enhances therapeutic antibody production in chinese hamster ovary cells.chinese hamster ovary (cho) cells are promising host engineering cells for industry manufacturing of therapeutic antibodies. however, cell death due to apoptosis remains a huge challenge to augment antibody production, and developing cho cells with enhanced anti-apoptosis and proliferation ability is fundamental for cell line development and high-yielding bioprocesses. deubiquitinase cylindromatosis (cyld) has been proved to be a tumor suppressor by negatively regulating nf-κb and wnt/β-catenin ...201829766242
antibody-assisted target identification reveals afatinib, an egfr covalent inhibitor, down-regulating ribonucleotide reductase.afatinib, used for the first-line treatment of non-small-cell lung carcinoma (nsclc) patients with distinct epidermal growth factor receptor (egfr) mutations, inactivates egfr by mimicking atp structure and forming a covalent adduct with egfr. we developed a method to unravel potential targets of afatinib in nsclc cells through immunoprecipitation of afatinib-labeling proteins with anti-afatinib antiserum and mass spectrometry analysis. ribonucleotide reductase (rnr) is one of target proteins of ...201829765556
a new cho (chinese hamster ovary)-derived cell line expressing anti-tnfα monoclonal antibody with biosimilar potential.tumor necrosis factor alpha (tnfα) is a pro-inflammatory cytokine that mediates the homeostasis of immune responses; its exacerbated production is associated with the pathogenesis of autoimmune and chronic inflammatory diseases. anti-tnfα drugs have revolutionized the treatment of inflammatory conditions such as rheumatoid arthritis and crohn's disease. currently, a worldwide race is on stage for the production of biosimilars moved by patent expiration of monoclonal antibodies (mabs), such as an ...201829855993
physiological responses of chinese hamster ovary cells to a productivity-enhancing yeast extract.hydrolysates play important roles in enhancing the productivity of recombinant proteins in mammalian cell cultures. lacking of detailed understanding of the mechanisms, hydrolysate is commonly regarded as an unstable factor which should be used with cautions. a yeast extract (ye) was approved to improve the fc-fusion protein productivity in a recombinant chinese hamster ovary (cho) cell line. to elucidate the responses of cells to hydrolysates, we further elaborate their physiological changes du ...201829853300
rapid development of stable transgene cho cell lines by crispr/cas9-mediated site-specific integration into c12orf35.chinese hamster ovary (cho) cells are the most widely used mammalian hosts for recombinant protein production. however, by conventional random integration strategy, development of a high-expressing and stable recombinant cho cell line has always been a difficult task due to the heterogenic insertion and its caused requirement of multiple rounds of selection. site-specific integration of transgenes into cho hot spots is an ideal strategy to overcome these challenges since it can generate isogenic ...201829789882
a crispr/cas9 based engineering strategy for overexpression of multiple genes in chinese hamster ovary cells.manipulation of multiple genes to engineer chinese hamster ovary (cho) cells for better performance in production processes of biopharmaceuticals has recently become more and more popular. yet, identification of useful genes and the unequivocally assessment of their effect alone and in combination(s) on the cellular phenotype is difficult due to high variation between subclones. here, we present development and proof-of-concept of a novel engineering strategy using multiplexable activation of ar ...201829852271
crispr/cas9-mediated gene knockout for dna methyltransferase dnmt3a in cho cells displays enhanced transgenic expression and long-term stability.cho cells are the preferred host for the production of complex pharmaceutical proteins in the biopharmaceutical industry, and genome engineering of cho cells would benefit product yield and stability. here, we demonstrated the efficacy of a dnmt3a-deficient cho cell line created by crispr/cas9 genome editing technology through gene disruptions in dnmt3a, which encode the proteins involved in dna methyltransferases. the transgenes, which were driven by the 2 commonly used cmv and ef1α promoters, ...201829851281
crispr-based targeted epigenetic editing enables gene expression modulation of the silenced beta-galactoside alpha-2,6-sialyltransferase 1 in cho cells.despite great efforts to control and modify gene expression of chinese hamster ovary (cho) cells by conventional genetic engineering approaches, i.e. overexpression or knockdown/-out, subclonal variation, induced unknown regulatory effects as well as overexpression stress are still a major hurdle for efficient cell line engineering and for unequivocal characterization of gene function. the use of epigenetic modulators - key players in cho clonal heterogeneity - has only been marginally addressed ...201829802757
cationic lipid/dna complexes manufactured by microfluidics and bulk self-assembly exhibit different transfection behavior.recent advances in biochemical and biophysical research have been achieved through the employment of microfluidic devices. microfluidic mixing of therapeutic agents with biomaterials yields systems with finely tuned physical-chemical properties for applications in drug and gene delivery. here, we investigate the role of preparation technology (microfluidic mixing vs. bulk self-assembly) on the transfection efficiency (te) and cytotoxicity of multicomponent cationic liposome/dna complexes (lipopl ...201829733845
the long non-coding rna transcriptome landscape in cho cells under batch and fed-batch conditions.the role of non-coding rnas in determining growth, productivity, and recombinant product quality attributes in chinese hamster ovary (cho) cells has received much attention in recent years, exemplified by studies into micrornas in particular. however, other classes of non-coding rnas have received less attention. one such class are the non-coding rnas known collectively as long non-coding rnas (lncrnas). the authors have undertaken the first landscape analysis of the lncrna transcriptome in cho ...201829781203
degradation of recombinant proteins by chinese hamster ovary host cell proteases is prevented by matriptase-1 knockout.an increasing number of nonantibody format proteins are entering clinical development. however, one of the major hurdles for the production of nonantibody glycoproteins is host cell-related proteolytic degradation, which can drastically impact developability and timelines of pipeline projects. chinese hamster ovary (cho) cells are the preferred production host for recombinant therapeutic proteins. using protease inhibitors, transcriptomics, and genetic knockdowns, we have identified, out of the ...201829777593
impact of a missense variation (p.s150r:agc>agg) in the xrcc2 gene on susceptibility to colorectal cancer.the x-ray repair complementing defective repair in chinese hamster cells 2 (xrcc2) is an important protein in response to dna double-strand breaks (dsbs) in human cells. xrcc2, as a functional protein in the homologous recombination repair (hrr) process, has been identified to have several polymorphisms which might be associated with the risk of cancer. therefore, we aimed to investigate a novel missense variation (agc>agg, p.ser150arg) in the xrcc2 gene for colorectal cancer susceptibility.201829739106
[effects of different promoters and mar combinations on transgene expression of recombinant cho cells].to analyze the effects of different promoters and matrix attachment region (mar) on the expression of transgene in chinese hamster ovary (cho) cells.201829737083
phase i trials of anti-enpp3 antibody-drug conjugates in advanced refractory renal cell carcinomas.purpose: to determine the safety, pharmacokinetics, and recommended phase ii dose of an antibody-drug conjugate (adc) targeting ectonucleotide phosphodiesterases-pyrophosphatase 3 (enpp3) conjugated to monomethyl auristatin f (mmaf) in subjects with advanced metastatic renal cell carcinoma (mrcc).patients and methods: two phase i studies were conducted sequentially with 2 adcs considered equivalent, hybridoma-derived ags-16m8f and chinese hamster ovary-derived ags-16c3f. ags-16m8f was administer ...201829848572
the effect of culture temperature on the aggregation of recombinant tnfr-fc is regulated by the perk-eif2a pathway in cho cells.recombinant human tumor necrosis factor receptor ⅱ-fc (tnfr-fc) is a therapeutic protein which is expressed in chinese hamster ovary (cho) cells. the desired tnfrfc is a dimeric form, however, polymeric tnfr-fc aggregation often occurs during cell culture which needs to be removed to minimize the potential risk of immunogenicity to patients. lowering the culture temperature is useful to improve the production of many recombinant proteins in cho cells.201829848262
zinc supplementation decreases galactosylation of recombinant igg in cho cells.trace element composition of culture medium can be altered to modulate glycoform of recombinant glycoproteins. in this study, we show that zn2+ supplementation at or above 100 μm decreases galactosylation of recombinant igg expressed in chinese hamster ovary cells. this decrease in galactosylation is not due to reduced galactosyltransferase expression. this effect persists upon supplementation of galactose and uridine to the culture, indicating that it may not be due to reduced udp-gal availabil ...201829749563
efficient mab production in cho cells with optimized signal peptide, codon, and utr.antibody drugs have been used to treat a number of diseases successfully. producing antibodies with high yield and quality is necessary for clinical applications of antibodies. for a candidate molecule, optimization of a vector to produce sufficient yield and an accurate primary structure is indispensable in the early stage of the production process development. it is especially important to maintain the fidelity of n-terminal sequence. in order to produce antibodies with a high yield and accura ...201829740673
uranyl acetate induced dna single strand breaks and ap sites in chinese hamster ovary cells.the aim of this study is to characterize the genotoxicity of depleted uranium (du) in chinese hamster ovary cells (cho) with mutations in various dna repair pathways. cho cells were exposed to 0-300 μm of soluble du as uranyl acetate (ua) for 0-48 h. intracellular ua concentrations were measured via inductively coupled mass spectrometry (icp-ms) and visualized by transmission electron microscopy (tem). cytotoxicity was assessed in vitro by clonogenic survival assay. dna damage response was asses ...201829698738
mpdu1 regulates ceacam1 and cell adhesion in vitro and in vivo.n-linked glycosylation (nlg) is a co-translational modification that is essential for the folding, stability, and trafficking of transmembrane (tm) and secretory glycoproteins. efficient nlg requires the stepwise synthesis and en bloc transfer of a 14-sugar carbohydrate known as a lipid-linked oligosaccharide (llo). the genetics of llo biosynthesis have been established in yeast and chinese hamster systems, but human models of llo biosynthesis are lacking. in this study we report that kato iii h ...201829671116
carbon dots-decorated na2w4o13 composite with wo3 for highly efficient photocatalytic antibacterial activity.photodisinfection by semiconductors has been proven to be an effective method for achieving antibacterial or antifungal activity. however, the toxicity of the nanomaterial to the environment and organisms is a major concern. herein, a highly efficient and environmentally friendly photodisinfection material of a carbon dots (cds) decorated na2w4o13 composite with wo3 photocatalyst was fabricated via a facile hydrothermal-calcination approach. the tem (transmission electron microscopy) images show ...201830007199
n-linked glycosylation modulates the immunogenicity of recombinant human factor viii in hemophilia a mice.immune responses to factor viii remain the greatest complication in the treatment of severe hemophilia a. recent epidemiological evidence has highlighted that recombinant factor viii produced in baby hamster kidney cells is more immunogenic than factor viii produced in chinese hamster ovary cells. glycosylation differences have been hypothesized to influence the immunogenicity of these synthetic concentrates. in two hemophilia a mouse models, baby hamster kidney cell-derived factor viii elicited ...201830002126
novel bivalent and d-peptide ligands of cxcr4 mobilize hematopoietic progenitor cells to the blood in c3h/hej mice.the interaction of sdf-1α (also known as cxcl12) with the cxcr4 receptor plays a critical role in the retention of hematopoietic stem cells (hscs) in bone marrow. the viral macrophage inflammatory protein-ii (vmip-ii), a human herpesvirus-8 (hhv-8)-encoded viral chemokine, can bind the cxcr4 receptor and inhibit endogenous ligand-induced calcium responses and cell migration. previously, we used the bivalent ligand approach to link synthetically two unnatural d-amino acid peptides derived from th ...201829991278
resveratrol ameliorates microcystin-lr-induced testis germ cell apoptosis in rats via sirt1 signaling pathway activation.microcystin-leucine arginine (mc-lr), a cyclic heptapeptide produced by cyanobacteria, is a strong reproductive toxin. studies performed in rat sertoli cells and chinese hamster ovary cells have demonstrated typical apoptosis after mc-lr exposure. however, little is known on how to protect against the reproductive toxicity induced by mc-lr. the present study aimed to explore the possible molecular mechanism underlying the anti-apoptosis and protective effects of resveratrol (res) on the co-cultu ...201829890735
control of amino acid transport into chinese hamster ovary cells.amino acid transporters (aats) represent a key interface between the cell and its environment, critical for all cellular processes: energy generation, redox control, and synthesis of cell and product biomass. however, very little is known about the activity of different functional classes of aats in chinese hamster ovary (cho) cells, how they support cell growth and productivity, and the potential for engineering their activity and/or the composition of amino acids in growth media to improve cho ...201829987891
genome sequence comparison between chinese hamster ovary (cho) dg44 cells and mouse using end sequences of cho bac clones based on bac-fish results.chinese hamster ovary (cho) cells have frequently been used in biotechnology as a mammalian host cell platform for expressing genes of interest. previously, we constructed a detailed physical chromosomal map of the cho dg44 cell line by fluorescence in situ hybridization (fish) imaging using 303 bacterial artificial chromosome (bac) clones as hybridization probes (bac-fish). bac-fish results revealed that the two longest chromosomes were completely paired. however, other chromosomes featured par ...201829987698
construction of anti-her2 recombinants as targeting modules for a drug-delivery system against her2-positive cells.recombinant antibodies have been investigated and used in applications such as targeting modules of drug-delivery systems (dds) against cancers. this study aimed to prepare recombinant antibodies against her2, containing sortase a (srta) recognition sequence, that are applicable as targeting modules in dds after linkage with the drug-carrier containing oligoglycine-acceptor peptide by srta transpeptidation.201829970568
chromawizard: an open source image analysis software for multicolor fluorescence in situ hybridization analysis.multicolor image analysis finds its applications in a broad range of biological studies. specifically, multiplex fluorescence in situ hybridization (m-fish) for chromosome painting facilitates the analysis of individual chromosomes in complex metaphase spreads and is widely used to detect both numerical and structural aberrations. while this is well established for human and mouse karyotypes, for which species sophisticated software and analysis tools are available, other organisms and species a ...201830089195
ph excursions impact cho cell culture performance and antibody n-linked glycosylation.ph excursions exist due to frequent base addition and environmental heterogeneity in large-scale bioreactors. such excursions could lead to suboptimal culture performance. here we investigated the impact of ph excursions on cell culture performance and n-linked glycosylation for three mab-producing chinese hamster ovary cell lines. frequent ph excursions were introduced by bolus base addition (in total 2-6% of initial volume, fixed bolus addition distributed from day 2 to 8) into small-scale bio ...201830088083
simulation and experimental study on the mechanism of the chlorination of azithromycin.azithromycin (azi) has been listed as an emerging contaminant by the us epa since 2009 because it is frequently detected in wastewater, surface water, and drinking water. in this paper, the chlorination of azi in drinking water was simulated and studied. the results indicated that new compounds were generated in the chlorination of azi. the byproducts were identified by liquid chromatography-quadrupole-time-of-flight mass spectrometry (lc-q-tof), and four of the byproducts were detected in real ...201830014912
generation of flp-intm-ready dg44 and lec 3.2.8.1 cho cell lines for quick and easy constitutive protein expression.the well-characterized cell line chinese hamster ovary (cho) has been used to produce numerous biopharmaceuticals and is an important tool for basic research. however, introducing foreign dna into specially modified cho cells such as dg44 and lec 3.2.8.1 can sometimes be an arduous process. here we show that the flp-intm plasmid can be modified to produce a fluorescent tracer protein tag (mcherrytm) as a fusion reporter, to allow for the rapid selection of single-cell sorted, isogenic flp-intm-r ...201830014730
differential expression of micrornas in recombinant chinese hamster ovary cells treated with sodium butyrate using digital rna counting.sodium butyrate (nabu) is an efficient supplement for increasing recombinant protein production in chinese hamster ovary (cho) cell culture. to elucidate the effects of nabu on mirna expression profile in recombinant cho (rcho) cells, differentially expressed mirnas in nabu-treated rcho cells were assessed by nanostring ncounter analysis. this result showed that eight mature mouse mirnas (let-7b, let-7d, mir-15b, mir-25, mir-27a, mir-99a, mir-125a-5p, and mir-125b-5p) were differentially express ...201830012463
improving the production of recombinant human bone morphogenetic protein-4 in chinese hamster ovary cell cultures by inhibition of undesirable endocytosis.endocytic regulation serves a critical role in modulating the extracellular level of signaling molecules, such as bone morphogenetic proteins (bmps). unfortunately, endocytosis may result in poor yields of recombinant human bmp-4 (rhbmp-4) from chinese hamster ovary (cho) cell cultures. when rhbmp-4 was incubated with cho cells, rhbmp-4 was actively internalized into cells. cell surface bound heparan sulfate proteoglycans (hspgs) served as the major receptors for rhbmp-4 internalization. removal ...201830011067
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