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a highly productive cho cell line secreting human blood clotting factor ix.hemophilia b patients suffer from an inherited blood-clotting defect and require regular administration of blood-clotting factor ix replacement therapy. recombinant human factor ix produced in cultured cho cells is nearly identical to natural, plasma-derived factor ix and is widely used in clinical practice. development of a biosimilar recombinant human factor ix for medical applications requires the generation of a clonal cell line with the highest specific productivity possible and a high leve ...202029713519
early detection of severe acute respiratory syndrome coronavirus 2 antibodies as a serologic marker of infection in patients with coronavirus disease 2019.thousands of medical staff have been infected with severe acute respiratory syndrome coronavirus 2 (sars-cov-2), with hundreds of deaths reported. such loss could be prevented if there were a serologic assay for sars-cov-2-specific antibodies for serological surveillance of its infection at the early stage of disease.202032357209
assessment of complex genomic alterations induced by azt, 3tc, and the combination azt +3tc.highly active antiretroviral therapy (haart) regimens are based on the use of nucleoside reverse transcriptase inhibitors (nrtis), which are the main drugs used by patients infected with the human immunodeficiency virus (hiv). the use of nrtis combinations has afforded clear clinical benefits to patients undergoing haart. however, the combination of two nrtis may increase the risk of genomic instability in comparison with the drugs administered individually. we analyzed the ability of zidovudine ...202030208744
the development and study of recombinant immunoglobulin a to hemagglutinins of the influenza virus.we obtained recombinant variants of human antibody fi6 broadly specific to hemagglutinins of the influenza a virus. on the basis of a bi-promoter (cmv, hef1-htlv) vector, we developed genetic constructs for the expression of the heavy and light chains of the immunoglobulins of iga1-, iga2m1-, and igg-isotypes. following transfection and selection, stable chinese hamster ovary (cho) cell lines were produced. the antibodies of iga1-, iga2m1-, and igg-isotypes were purified from culture media. we p ...202030116613
assuring clonality on the beacon digital cell line development platform.during biomanufacturing cell lines development, the generation and screening for single-cell derived subclones using methods that enable assurance of clonal derivation can be resource- and time-intensive. high-throughput miniaturization, automation, and analytic strategies are often employed to reduce such bottlenecks. the beacon platform from berkeley lights offers a strategy to eliminate these limitations through culturing, manipulating, and characterizing cells on custom nanofluidic chips via ...202031743597
resveratrol addition to chinese hamster ovary cell culture media: the effect on cell growth, monoclonal antibody synthesis, and its chemical modification.the effect of the addition of resveratrol to cell culture media during the production of monoclonal antibodies was investigated. treatments of chinese hamster ovary (cho) cells expressing immunoglobulin g (igg) with 25 and 50 μm resveratrol showed that resveratrol was capable of slowing cell growth while almost doubling cell-specific productivity to 4.7 ± 0.6 pg igg/cell·day, resulting in up to a 1.37-fold increase of the final igg titer. a resveratrol concentration of 50 μm slowed the progressi ...202031742929
comparative cytotoxicity of halogenated aromatic dbps and implications of the corresponding developed qsar model to toxicity mechanisms of those dbps: binding interactions between aromatic dbps and catalase play an important role.halogenated aromatic disinfection byproducts (dbps) are a new group of emerging dbps identified recently. they have been detected in disinfected drinking water, wastewater effluents, recreational water and oil/gas produced water, at concentrations of ng/l to μg/l in general. previously studies have demonstrated that most of them can induce developmental toxicity and growth inhibition in aquatic organisms based on in vivo bioassays. in this study, to further understand the adverse effects of arom ...202031739241
an agonist radioligand for the proinflammatory lipid-activated g protein-coupled receptor gpr84 providing structural insights.the orphan g protein-coupled receptor (gpcr) gpr84 is expressed on immune cells mediating proinflammatory and immunostimulatory effects. in this study, we prepared the fully efficacious, nonbiased gpr84 agonist 6-hexylamino-2,4(1h,3h)-pyrimidinedione (6) in tritium-labeled form ([3h]psb-1584) by hydrogenation of a hexenyl-substituted precursor with tritium gas. the radioligand was characterized by kinetic, saturation, and competition assays using membranes of chinese hamster ovary cells recombin ...202031721581
an easy and fast method for production of chinese hamster ovary cell line expressing and secreting human recombinant activin a.growth factors are key elements of embryonic stem cell (esc) research. cell line development in eukaryotes is a time-consuming procedure which usually takes 12-18 months. here, we report an easy and fast method with which production of chinese hamster ovary (cho) cells that express and secrete recombinant activin a, as a major growth factor in endo/mesoderm differentiation of embryonic stem cells is achieved within 3-4 weeks.202031721527
engineering of chinese hamster ovary cell lipid metabolism results in an expanded er and enhanced recombinant biotherapeutic protein production.chinese hamster ovary (cho) cell expression systems have been exquisitely developed for the production of recombinant biotherapeutics (e.g. standard monoclonal antibodies, mabs) and are able to generate efficacious, multi-domain proteins with human-like post translational modifications at high concentration with appropriate product quality attributes. however, there remains a need for development of new cho cell expression systems able to produce more challenging secretory recombinant biotherape ...202031805379
dr10601, a novel recombinant long-acting dual glucagon-like peptide-1 and glucagon receptor agonist for the treatment of obesity and type 2 diabetes mellitus.both glucagon-like peptide-1 (glp-1) and glucagon (gcg) belong to the incretin family. this study aimed to investigate the pharmacokinetics and pharmacodynamics of dr10601, a fully recombinant hybrid peptide with dual glp-1/gcg receptor agonistic activity.202031786794
modelling of hollow fiber membrane bioreactor for mammalian cell cultivation using computational hydrodynamics.the hollow fiber membrane bioreactor (hfmb) has been investigated for the cultivation of mammalian chinese hamster ovary cell expansion. the experiments were carried out in petri's dishes and in the hollow fiber membrane bioreactor having 20 fibers (s2025 from fibercell systems). the approach to hfmb modelling which combines the model of cell growth kinetics and hydrodynamics has been proposed. the hydrodynamic model is made using ansys fluent software. the mathematical model of hfmb was develop ...202031786664
microrna-504 functions as a tumor suppressor in oral squamous cell carcinoma through inhibiting cell proliferation, migration and invasion by targeting cdk6.microrna (mirna), as tumor suppressor or oncogene, is involved in the regulation of tumor development. however, the role of mirna in human oral squamous cell carcinoma (oscc) is less well understood. in our previous studies, we have successfully established a chinese hamster oral squamous cell carcinoma animal model and constructed a mirna differential expression profile, and screened out the abnormal expressed gene (mir-504). the purpose of this study was to investigate the regulatory mechanism ...202031812760
knockout of sialidase and pro-apoptotic genes in chinese hamster ovary cells enables the production of recombinant human erythropoietin in fed-batch cultures.sialic acid, a terminal monosaccharide present in n-glycans, plays an important role in determining both the in vivo half-life and the therapeutic efficacy of recombinant glycoproteins. low sialylation levels of recombinant human erythropoietin (rhepo) in recombinant chinese hamster ovary (rcho) cell cultures are considered a major obstacle to the production of rhepo in fed-batch mode. this is mainly due to the accumulation of extracellular sialidases released from the cells. to overcome this hu ...202031785386
bioinformatic identification of chinese hamster ovary (cho) cold-shock genes and biological evidence of their cold-inducible promoters.lower cultivation temperature dramatically affects cell growth and cellular productivity in chinese hamster ovary cells (cho) and is often used in industrial applications with the aim to enhance productivity. cold-inducible proteins whose activity is induced at lower temperature play an important role in understanding the mechanisms of cold-induced changes in gene expression. one of these mechanisms is increased transcription of specific target genes controlled by sequence elements in cold-induc ...202031785035
unaccompanied mechanosensory domain mediates low expression of glycoprotein ibα: implications for bernard-soulier syndrome.disruption of protein folding or inter-subunit interactions in the platelet glycoprotein (gp)ib-ix complex leads to its abnormally low expression in the plasma membrane, the hallmark of bernard-soulier syndrome (bss).202031749281
ercc1 c8092a polymorphism predicts fair survival outcome in japanese patients with pharyngo-laryngeal squamous cell carcinoma.to evaluate the prognostic significance of dna excision repair gene polymorphisms, excision repair cross-complementation group 1 (ercc1) and x-ray repair complementing defective repair in chinese hamster cells 1 (xrcc1) polymorphisms were investigated in japanese patients with head and neck squamous cell carcinoma (hnscc).202031749055
effects of cysteine, asparagine, or glutamine limitations in chinese hamster ovary cell batch and fed-batch cultures.amino acid availability is a key factor that can be controlled to optimize the productivity of fed-batch cultures. to study amino acid limitation effects, a serum-free chemically defined basal medium was formulated to exclude the amino acids that became depleted in batch culture. the effect of limiting glutamine, asparagine, and cysteine on the cell growth, metabolism, antibody productivity, and product glycosylation was investigated in three chinese hamster ovary (cho) cell lines (cho-dxb11, ch ...202031823468
polymorphisms and endometriosis: a systematic review and meta-analyses.endometriosis is an estrogen-dependent gynecological disorder that affects at least 10% of women of reproductive age. it may lead to infertility and non-specific symptoms such as chronic pelvic pain. endometriosis screening and diagnosis are difficult and time-consuming. late diagnosis (with a delay ranging from 3.3 to 10.7 years) is a major problem and may contribute to disease progression and a worse response to treatment once initiated. efficient screening tests might reduce this diagnostic d ...202031821471
a novel method based on nonparametric regression with a gaussian kernel algorithm identifies the critical components in cho media and feed optimization.as the composition of animal cell culture medium becomes more complex, the identification of key variables is important for simplifying and guiding the subsequent medium optimization. however, the traditional experimental design methods are impractical and limited in their ability to explore such large feature spaces. therefore, in this work, we developed a nrgk (nonparametric regression with gaussian kernel) method, which aimed to identify the critical components that affect product titres duri ...202031754859
oxidative stress-alleviating strategies to improve recombinant protein production in cho cells.large scale biopharmaceutical production of biologics relies on the overexpression of foreign proteins by cells cultivated in stirred tank bioreactors. it is well recognized and documented fact that protein overexpression may impact host cell metabolism and that factors associated with large scale culture, such as the hydrodynamic forces and inhomogeneities within the bioreactors, may promote cellular stress. the metabolic adaptations required to support the high-level expression of recombinant ...202031814104
profiles of plant core-fucosylated n-glycans of acid alpha-glucosidases produced in transgenic rice cell suspension cultures treated with eight different conditions.recombinant human acid alpha-glucosidase (rhgaa) from chinese hamster ovary cells is the only approved treatment for patients with pompe disease. in this study, rhgaas were produced in transgenic rice cell suspension cultures under eight different conditions; untreated, 5 μm of 2-fluoro-l-fucose (2-ff), 50 μm of 2-ff, 100 μm of 2-ff, 100 μm of 2-ff + 0.5% pluronic f-68 (pf-68), 100 μm of 2-ff + 0.05% tween 20 (tw 20), 0.5% pf-68, and 0.05% tw 20. the n-glycans of eight rhgaas were analyzed using ...202032044029
c1q/tnf-related protein 6 is a pattern recognition molecule that recruits collectin-11 from the complement system to ligands.c1q/tnf-related protein (ctrp) 6 is a member of the ctrp protein family associated with the regulation of cellular and endocrine processes. ctrp6 contains collagen and globular structures, resembling the pattern recognition molecules (prms) of the classical and lectin complement pathways. we expressed human ctrp6 in chinese hamster ovary cells and investigated the binding to different putative ligands (acetylated bsa [acbsa], zymosan, mannan, and lps from escherichia coli and salmonella as well ...202032041782
role of a new bioassay for thyroid-stimulating antibodies (aequorin tsab) in graves' ophthalmopathy.graves' ophthalmopathy (go) is characterized by an autoimmune reaction against thyrotropin (tsh) receptors and is diagnosed by tsh receptor antibody (trab). a novel assay for thyroid-stimulating antibody (tsab) was recently introduced using a frozen chinese hamster ovary cell line expressing tsh receptors, cyclic adenosine monophosphate (camp)-gated calcium channel, and aequorin (aequorin tsab). the aim of this study was to evaluate the role of aequorin tsab in go. we studied 136 japanese patien ...202031827052
reinvestigation of disulfide-bonded oligomeric forms of the unfolded protein response transducer atf6.atf6α is an endoplasmic reticulum (er)-embedded transcription factor which is rapidly activated by er stress, and a major regulator of er chaperone levels in vertebrates. we previously suggested that atf6α occurs as a monomer, dimer and oligomer in the unstressed er of chinese hamster ovary cells due to the presence of two evolutionarily conserved cysteine residues in its luminal region (c467 and c618), and showed that atf6α is reduced upon er stress, such that only reduced monomer atf6α is tran ...202031852864
hif-1 signaling pathway implicated in phenotypic instability in a chinese hamster ovary production cell line.monitoring genotypic and phenotypic stability is crucial during the development of recombinant chinese hamster ovary (cho) cell lines. although genotypic instability is well-studied, there are few reports on phenotypic instability. here, a case study of two clonal cell lines derived from pfizer's site-specific integration expression platform that expresses the same monoclonal antibody is described. it is shown that both cell lines (herein referred to as "cell line a" and "cell line b") are genot ...202031872551
investigating toxicity of urban road deposited sediments using chinese hamster ovary cells and chlorella pyrenoidosa.road deposited sediments (rds) is the key carrier of pollutants in the urban road stormwater processes and hence has been seen as an important pollutant source of urban road stormwater. although many research studies have focused on rds and pollutants attached to rds, the investigation on rds toxicity is very limited. toxicity test can permit an overall assessment on whether the rds polluted stormwater can be safely reused. this paper used two living organisms, namely chinese hamster ovary (cho) ...202031864047
orbitally shaken single-use bioreactor for animal cell cultivation: fed-batch and perfusion mode.increasing the cultivation volume from small to large scale can be a rather complex and challenging process when the method of aeration and mixing is different between scales. orbitally shaken bioreactors (osbs) utilize the same hydrodynamic principles that define the success of smaller-scale cultures, which are developed on an orbitally shaken platform, and can simplify scale-up. here we describe the basic working principles of scale-up in terms of the volumetric oxygen transfer coefficient (kl ...202031858465
using a parallel micro-cultivation system (micro-matrix) as a process development tool for cell culture applications.micro-bioreactors appear frequently in today's biotechnology industry as screening and process development tools for cell culture applications. the micro-bioreactor's small volume allows for a high throughput, and when compared to other small-scale systems, such as microtiter plates, its measurement and control capabilities offer a much better insight into the bioprocess. applikon's micro-matrix is one of the micro-bioreactors that are commercially available today. the micro-matrix system consis ...202031858463
biallelic loss-of-function mutations in jam2 cause primary familial brain calcification.primary familial brain calcification is a monogenic disease characterized by bilateral calcifications in the basal ganglia and other brain regions, and commonly presents motor, psychiatric, and cognitive symptoms. currently, four autosomal dominant (slc20a2, pdgfrb, pdgfb, xpr1) and one autosomal recessive (myorg) causative genes have been identified. compared with patients with autosomal dominant primary familial brain calcification, patients with the recessive form of the disease present with ...202031851307
investigation and circumvention of transfection inhibition by ferric ammonium citrate in serum-free media for chinese hamster ovary cells.while reliable transfection methods are essential for chinese hamster ovary (cho) cell line engineering, reduced transfection efficiencies have been observed in several commercially prepared media. in this study, we aimed to assess common media additives that impede efficiency mediated by three chemical transfection agents: liposomal-based (lipofectamine 2000), polymer-based (transit-x2), and lipopolyplex-based (transit-pro). an in-house gfp-expressing vector and serum-free medium (bcr-f12: deve ...202031850663
validation and identification of reference genes in chinese hamster ovary cells for fc-fusion protein production.in order to reveal potential genotype-phenotype relationship, rt-qpcr reactions are frequently applied which require validated and reliable reference genes. with the investigation on long-term passage and fed-batch cultivation of cho cells producing an fc-fusion protein, four new reference genes-akr1a1, gpx1, aprt, and rps16, were identified from 20 candidates with the aid of genorm, normfinder, bestkeeper, and δct programs and methods. this article provided more verified options in reference ge ...202032216463
pharmacological properties of whale shark (rhincodon typus) melanocortin-2 receptor and melancortin-5 receptor: interaction with mrap1 and mrap2.in the current study, the whale shark (ws; rhincodon typus) melanocortin-2 receptor (mc2r) co-expressed with wsmrap1 in chinese hamster ovary (cho) cells could be stimulated in a dose dependent manner by acth(1-24) with an ec50 of 2.6 × 10-10 m ± 9.7 × 10-11. when the receptor was expressed alone, stimulation was only observed at [10-6 m]. a comparable increase in sensitivity to stimulation by srdes-ac-αmsh was also observed when the receptor was co-expressed with wsmrap1. in addition, co-expres ...202032213301
a metabolic network-based approach for developing feeding strategies for cho cells to increase monoclonal antibody production.chinese hamster ovary (cho) cells are the main workhorse in the biopharmaceutical industry for the production of recombinant proteins, such as monoclonal antibodies. to date, a variety of metabolic engineering approaches have been used to improve the productivity of cho cells. while genetic manipulations are potentially laborious in mammalian cells, rational design of cho cell culture medium or efficient fed-batch strategies are more popular approaches for bioprocess optimization. in this study, ...202032211960
insights into virus inactivation by polysorbate 80 in the absence of solvent.triton x-100 has long been used either alone or in combination with solvent to inactivate enveloped viruses in biopharmaceutical manufacturing. however, european chemicals agency (echa) officially placed triton x-100 on the annex xiv authorization list in 2017 because 4-(1,1,3,3-tetramethylbutyl) phenol, a degradation product of triton x-100, is of harmful endocrine disrupting activities. as a result, any use of triton x-100 in the european economic area would require an echa issued authorizatio ...202031846227
altered gene expression in cho cells following polyamine starvation.to investigate the impact of polyamine deprivation on the transcriptome of cho cells results: polyamines play a central but poorly-understood role in cell proliferation. most studies to date have utilised chemical inhibitors to probe polyamine function. here we exploit the fact that cho cells grown in serum-free medium have an absolute requirement for putrescine supplementation due to their deficiency in activity of the enzyme arginase. a gene expression microarray (affymetrix) analysis of cho-k ...202032078082
improvement of intracellular traffic system by overexpression of kdel receptor 1 in antibody-producing cho cells.the localization of soluble endoplasmic reticulum (er) chaperones in the cell organelle is mediated by the c-terminal kdel (lysine, aspartic acid, glutamic acid and leucine) motif. this motif is recognized by the kdel receptor, a seven-transmembrane protein that cycles between the er and cis-golgi to capture missorted kdel chaperones from post-er compartments in a ph-dependent manner. the kdel receptor's target chaperones have a substantial role in protein folding and assembly. in this study, th ...202032073237
endothelial intercellular cell adhesion molecule 1 contributes to cell aggregate formation in cho cells cultured in serum-free media.chinese hamster ovary (cho) cells have been adapted to grow in serum-free media and in suspension culture to facilitate manufacturing needs. some cho cell lines, however, tend to form cell aggregates while being cultured in suspension. this can result in reduced viability and capacity for single cell cloning (scc) via limiting dilution, and process steps to mitigate cell aggregate formation, for example, addition of anti-cell-aggregation agents. in this study, we have identified endothelial inte ...202031846224
surrogates for the removal by ozonation of the cytotoxicity and dna double-strand break effects of wastewater on mammalian cells.effluents from wastewater treatment plants (wwtps) may contain various pollutants with potential toxic effects. ozonation is widely applied to purify wastewater, which may influence the toxicity and water quality indices simultaneously. the main goal of this study was to reveal influence of ozonation on toxicity of wwtp effluents and to find the surrogates for toxicity changes. cytotoxicity and dna double-strand break (dsb) effect of wwtp effluents were measured based on chinese hamster ovary (c ...202031841803
lipid catabolism in starved yak is inhibited by intravenous infusion of β-hydroxybutyrate.lipid is the chief energy source for starved animals. β-hydroxybutyrate (bhba) is the main ketone body produced by lipid decomposition. in chinese hamster ovary (cho) cell experiment, it was found that bhba could be used not only as an energy substance, but also as a ligand of gpr109a for regulating lipid metabolism. however, whether bhba can regulate lipid metabolism of yaks, and its effective concentration and signal pathway are not clear. this study investigated the effects and mechanism of s ...202031952136
3-quinuclidinyl-α-methoxydiphenylacetate: a multi-targeted ligand with antimuscarinic and antinicotinic effects designed for the treatment of anticholinesterase poisoning.racemic 3-quinuclidinyl-α-methoxydiphenylacetate (mb266) was synthesised. its activity at muscarinic acetylcholine receptors (machrs), and muscle and neuronal nicotinic acetylcholine receptors (nachrs), was compared to that of atropine and racemic 3-quinucidinyl benzilate (qnb) using a functional assay based on agonist-induced elevation of intracellular calcium ion concentration in cn21, chinese hamster ovary (cho) and shsy5y human cell lines. mb266 acted as an antagonist at acetylcholine recept ...202032017982
analysis of chemometric models applied to raman spectroscopy for monitoring key metabolites of cell culture.the food and drug administration (fda) initiative of process analytical technology (pat) encourages the monitoring of biopharmaceutical manufacturing processes by innovative solutions. raman spectroscopy and the chemometric modeling tool partial least squares (pls) have been applied to this aim for monitoring cell culture process variables. this study compares the chemometric modeling methods of support vector machine radial (svmr), random forests (rf), and cubist to the commonly used linear pls ...202032012476
feeding tricarboxylic acid cycle intermediates improves lactate consumption and antibody production in chinese hamster ovary cell cultures.media components play an important role in modulating cell metabolism and improving product titer in mammalian cell cultures. to sustain cell productivity, highly active oxidative metabolism is desired. here we explored the effect of tricarboxylic acid (tca) cycle intermediates supplementation on lactate metabolism and productivity in chinese hamster ovary fed-batch cultures. direct addition of 5 mm alpha-ketoglutarate (α-kg), malic acid, or succinic acid in the basal medium did not have any sig ...202032012447
structure-function relationships of the soluble form of the antiaging protein klotho have therapeutic implications for managing kidney disease.the fortuitously discovered antiaging membrane protein αklotho (klotho) is highly expressed in the kidney, and deletion of the klotho gene in mice causes a phenotype strikingly similar to that of chronic kidney disease (ckd). klotho functions as a co-receptor for fibroblast growth factor 23 (fgf23) signaling, whereas its shed extracellular domain, soluble klotho (sklotho), carrying glycosidase activity, is a humoral factor that regulates renal health. low sklotho in ckd is associated with diseas ...202032005658
cell electropermeabilisation enhancement by non-thermal-plasma-treated pbs.the effectiveness of electrochemotherapy (ect) in local eradication of tumours in human and veterinary medicine has been proven. ect consists of increasing the uptake of cytotoxic drugs by means of pulsed electric fields (pefs) that transiently permeabilise the cell membrane. still, this tumour treatment includes some drawbacks that are linked to the characteristics of the intense electric pulses (eps) used. meanwhile, the emerging field of cancer therapies that are based on the application of n ...202031963132
attenuating apoptosis in chinese hamster ovary cells for improved biopharmaceutical production.chinese hamster ovary (cho) cells are the predominant host cell line for the production of biopharmaceuticals, a growing industry currently worth more than $188 billion usd in global sales. cho cells undergo programmed cell death (apoptosis) following different stresses encountered in cell culture, such as substrate limitation, accumulation of toxic by-products, and mechanical shear, hindering production. genetic engineering strategies to reduce apoptosis in cho cells have been investigated with ...202031930480
kinetic modeling of chinese hamster ovary cell culture: factors and principles.as a host for therapeutic protein expression, chinese hamster ovary (cho) cells are widely utilized in the mainstream biopharmaceutical industry. cell culture process development plays an important role in transitioning laboratory research to manufacturing. among different mathematic tools, kinetic modeling is commonly achieved through analyzing cell culture data to design process parameters, optimize media, and scale up bioreactors. in this review, we examine key factors for upstream process de ...202031928250
targeted optical imaging of the glucagonlike peptide 1 receptor using exendin-4-irdye 800cw.the treatment of choice for insulinomas and focal lesions in congenital hyperinsulinism (chi) is surgery. however, intraoperative detection can be challenging. this challenge could be overcome with intraoperative fluorescence imaging, which provides real-time lesion detection with a high spatial resolution. here, a novel method for targeted near-infrared (nir) fluorescence imaging of glucagonlike peptide 1 receptor (glp-1r)-positive lesions, using the glp-1 agonist exendin-4 labeled with irdye 8 ...202031924726
defining lncrnas correlated with cho cell growth and igg productivity by rna-seq.how the long non-coding rna (lncrna) genome in recombinant protein producing chinese hamster ovary (cho) cell lines relates to phenotype is not well described. we therefore defined the cho cell lncrna transcriptome from cells grown in controlled miniature bioreactors under fed-batch conditions using rna-seq to identify lncrnas and how the expression of these changes throughout growth and between igg producers. we identify lncrnas including adapt15, linked to er stress, gas5, linked to mtor signa ...202031962234
different localization of lysosomal-associated membrane protein 1 (lamp1) in mammalian cultured cell lines.lysosomal-associated membrane protein 1 (lamp1) mainly localizes to lysosomes and late endosomes. we herein investigated the intracellular localization of lysosomal membrane proteins in five mammalian cultured cell lines. rat lamp1 fused to enhanced green fluorescent protein (egfp) mostly accumulated at a particular cytoplasmic area and barely co-localized with lysotracker® red dnd-99 in golden hamster kidney bhk-21 cells and chinese hamster ovary cho-k1 cells. golden hamster, chinese hamster, a ...202031907597
how to produce mabs in a cube-shaped stirred single-use bioreactor at 200 l scale.single-use bioreactors have increasingly been used in recent years, for both research and development as well as industrial production, especially in mammalian cell-based processes. among the numerous single-use bioreactors available today, wave-mixed bags and stirred systems dominate. wave-mixed single-use bioreactors are the system of choice for inoculum production, while stirred single-use bioreactors are most often preferred for antibody expression. for this reason, the present chapter descr ...202031858468
choice of host cell line is essential for the functional glycosylation of the fc region of human igg1 inhibitors of influenza b viruses.abs are glycoproteins that carry a conserved n-linked carbohydrate attached to the fc whose presence and fine structure profoundly impacts on their in vivo immunogenicity, pharmacokinetics, and functional attributes. the host cell line used to produce igg plays a major role in this glycosylation, as different systems express different glycosylation enzymes and transporters that contribute to the specificity and heterogeneity of the final igg-fc glycosylation profile. in this study, we compare tw ...202031907284
direct optical detection of cell density and viability of mammalian cells by means of uv/vis spectroscopy.the critical process parameters cell density and viability during mammalian cell cultivation are assessed by uv/vis spectroscopy in combination with multivariate data analytical methods. this direct optical detection technique uses a commercial optical probe to acquire spectra in a label-free way without signal enhancement. for the cultivation, an inverse cultivation protocol is applied, which simulates the exponential growth phase by exponentially replacing cells and metabolites of a growing ch ...202031897554
genome-scale reconstructions of the mammalian secretory pathway predict metabolic costs and limitations of protein secretion.in mammalian cells, >25% of synthesized proteins are exported through the secretory pathway. the pathway complexity, however, obfuscates its impact on the secretion of different proteins. unraveling its impact on diverse proteins is particularly important for biopharmaceutical production. here we delineate the core secretory pathway functions and integrate them with genome-scale metabolic reconstructions of human, mouse, and chinese hamster ovary cells. the resulting reconstructions enable the c ...202031896772
summation of disinfection by-product cho cell relative toxicity indices: sampling bias, uncertainty, and a path forward.the cyto- and genotoxic potencies of disinfection by-products (dbps) have been evaluated in published literature by measuring the response of exposed chinese hamster ovary cells. in recent publications, dbp concentrations divided by their individual toxicity indices are summed to predict the relative toxicity of a water sample. we hypothesized that the omission or inclusion of certain dbps over others is equivalent to statistical sampling bias and may result in biased conclusions. to test this h ...202031894210
robust analytical methods for the accurate quantification of the total biomass composition of mammalian cells.biomass composition is an important input for genome-scale metabolic models and has a big impact on their predictive capabilities. however, researchers often rely on generic data for biomass composition, e.g. collected from similar organisms. this leads to inaccurate predictions, because biomass composition varies between different cell lines, conditions, and growth phases. in this chapter we present protocols for the determination of the biomass composition of chinese hamster ovary (cho) cells. ...202031893373
small-scale bioreactor supports high density hek293 cell perfusion culture for the production of recombinant erythropoietin.process intensification in mammalian cell culture-based recombinant protein production has been achieved by high cell density perfusion exceeding 108 cells/ml in the recent years. as the majority of therapeutic proteins are produced in chinese hamster ovary (cho) cells, intensified perfusion processes have been mainly developed for this type of host cell line. however, the use of cho cells can result in non-human posttranslational modifications of the protein of interest, which may be disadvanta ...202031891733
cytotoxicity and genotoxicity of dmabee, a co-photoinitiator of resin polymerization, on cho-k1 cells: role of redox and carboxylesterase.the 4-dimethylaminobenzoic acid ethyl ester (dmabee) is an important co-initiator for resin polymerization in dental resinous materials. as a radical forming chemical with high lipophilicity, the genotoxicity and cytotoxicity of dmabee deserve prudent investigation. in this study, we found that dmabee reduced the viability and proliferation of chinese hamster ovary (cho-k1) cells in a dose-dependent manner, and altered cell morphology at higher concentrations. g0/g1 cell cycle arrest was induced ...202031880385
macrophages show higher levels of engulfment after disruption of cis interactions between cd47 and the checkpoint receptor sirpα.the macrophage checkpoint receptor sirpα signals against phagocytosis by binding cd47 expressed on all cells - including macrophages. here, we found that inhibiting cis interactions between sirpα and cd47 on the same macrophage increased engulfment ('eating') by approximately the same level as inhibiting trans interactions. antibody blockade of cd47, as pursued in clinical trials against cancer, was applied separately to human-derived macrophages and to red blood cell (rbc) targets for phagocyto ...202031964705
inhibition of endogenous mir-23a/mir-377 in cho cells enhances difficult-to-express recombinant lysosomal sulfatase activity.difficult-to-express (dte) recombinant proteins such as multi-specific proteins, dte monoclonal antibodies, and lysosomal enzymes have seen difficulties in manufacturability using chinese hamster ovary (cho) cells or other mammalian cells as production platforms. cho cells are preferably used for recombinant protein production for their ability to secrete human-like recombinant proteins with posttranslational modification, resistance to viral infection, and familiarity with drug regulators. howe ...202031990124
cytotoxic and genotoxic assessments of 2,4-dichlorophenoxyacetic acid (2,4-d) in in vitro mammalian cells.a combined approach employing alkaline single cell gel electrophoresis (scge) and cytokinesis-blocked micronucleus (mns) cytome bioassays was adopted to assess the deleterious properties of the auxinic 2,4-dichlorophenoxyacetic acid (2,4-d) and its microparticulated low volatility product dedalo elite (30% a.i.) on chinese hamster ovary (cho-k1) cells. cytotoxicity was estimated by neutral red uptake (nru), succinic dehydrogenase activity (mtt) and apoptosis assessment. both compounds were assay ...202031987841
engineering mammalian cells to produce plant-specific n-glycosylation on proteins.protein n-glycosylation is an essential and highly conserved posttranslational modification found in all eukaryotic cells. yeast, plants and mammalian cells, however, produce n-glycans with distinct structural features. these species-specific features not only pose challenges in selecting host cells for production of recombinant therapeutics for human medical use but also provide opportunities to explore and utilize species-specific glycosylation in design of vaccines. here, we used reverse cros ...202032039452
the epilepsy of infancy with migrating focal seizures: identification of de novo mutations of the kcnt2 gene that exert inhibitory effects on the corresponding heteromeric kna1.1/kna1.2 potassium channel.the epilepsy of infancy with migrating focal seizures (eimfs; previously called malignant migrating partial seizures of infancy) are early-onset epileptic encephalopathies (eoee) that associate multifocal ictal discharges and profound psychomotor retardation. eimfs have a genetic origin and are mostly caused by de novo mutations in the kcnt1 gene, and much more rarely in the kcnt2 gene. kcnt1 and kcnt2 respectively encode the kna1.1 (slack) and kna1.2 (slick) subunits of the sodium-dependent vol ...202032038177
heterozygous variant fibrinogen γa289v (kanazawa iii) was confirmed as hypodysfibrinogenemia by plasma and recombinant fibrinogens.congenital fibrinogen disorders are classified as afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia. however, difficulties are associated with discriminating between dysfibrinogenemia, hypofibrinogenemia, and hypodysfibrinogenemia using routine analyses. we previously reported a heterozygous variant fibrinogen (γa289v; kanazawa iii) as hypodysfibrinogenemia; however, the same variant had previously been described as hypofibrinogenemia. to clarify the production of ...202031957968
influence of cytoskeleton organization on recombinant protein expression by cho cells.in this study, we assessed the importance of cytoskeleton organization in the mammalian cells used to produce therapeutic proteins. two cytoskeletal genes, actin alpha cardiac muscle 1 (actc1) and a guanosine triphosphate gtpase-activating protein (tagap), were found to be upregulated in highly productive therapeutic protein-expressing chinese hamster ovary (cho) cells selected by the deprivation of vitamin b5. we report here that the overexpression of the actc1 protein was able to improve signi ...202031956990
overexpression of transcription factor foxa1 and target genes remediate therapeutic protein production bottlenecks in chinese hamster ovary cells.despite extensive research conducted to increase protein production from chinese hamster ovary (cho) cells, cellular bottlenecks often remain, hindering high yields. in this study, a transcriptomic analysis led to the identification of 32 genes that are consistently upregulated in high producer clones and thus might mediate high productivity. candidate genes were associated with functions such as signaling, protein folding, cytoskeleton organization, and cell survival. we focused on two engineer ...202031956982
inhibition of cholesteryl ester synthesis by polyacetylenes from atractylodes rhizome.using activity guided purification, four known compounds, sesquiterpene atractylenolide iii (1), and the polyacetylenes 14-acetoxy-12-senecioyloxytetradeca-2e,8e,10e-trien-4,6-diyn-1-ol (2), 14-acetoxy-12-α-methylbutyl-2e,8e,10e-trien-4,6-diyn-1-ol (3), and 14-acetoxy-12-β -methylbutyl-2e,8e,10e-trien-4,6-diyn-1-ol (4), were isolated from a traditional herbal medicine, atractylodes rhizome. structurally similar 3 and 4 (3/4 mixture) were obtained as a mixture. in intact chinese hamster ovary (ch ...202032035699
recombinant β-glucocerebrosidase specific immunoaffinity ligands selected from phage-displayed combinatorial scfv libraries.antibodies specific to β-glucocerebrosidase were selected from phage displayed naïve scfv libraries. biopannings were performed against recombinant human protein β-glucocerebrosidase immobilized on polystyrene surface, specific phages were eluted with 50% ethylene glycol in citrate buffer (ph 6.0). several specific binders were discovered and converted to full-size higg1 antibodies leading to highly stable binders with dissociation constants (kd) in the range 10-40 nm. the antibodies were used f ...202031981620
glucose monitoring in cell culture with online ultrasound-assisted near-infrared spectroscopy.near-infrared (nir) spectroscopic analysis for suspensions often requires a pretreatment by dilution or filtering of suspended solids to maintain the sensitivity of the measurements. an online ultrasound-assisted spectroscopy (uas) unit enabling pretreatment-free and noncontact analysis for bioprocessing is proposed and evaluated with a model suspension containing 3-μm-diameter polystyrene latex particles (psls) with the density of 5.1 × 108 counts/ml and chinese hamster ovary (cho) cell culture ...202032023047
an efficient exogenous gene insertion site in cho cells with high transcription level to enhance aid-induced mutation.antibodies have been extensively used for the purpose of scientific research, clinical diagnosis, and therapy. combination of in vitro somatic hypermutation and mammalian cell surface display has been an efficient technology for antibody or other proteins optimization, in which the efficiency of activation-induced cytidine deaminase (aid) mutations in genes is one of the most important key factors. gene transcriptional level has been found to be positively proportional to aid-induced mutation fr ...202031975519
maximizing antibody production in a targeted integration host by optimization of subunit gene dosage and position.historically, therapeutic protein production in chinese hamster ovary (cho) cells has been accomplished by random integration (ri) of expression plasmids into the host cell genome. more recently, the development of targeted integration (ti) host cells has allowed for recombination of plasmid dna into a predetermined genomic locus, eliminating one contributor to clone-to-clone variability. in this study, a ti host capable of simultaneously integrating two plasmids at the same genomic site was use ...202031965756
differential effects of 2-hydroxypropyl-cyclodextrins on lipid accumulation in npc1-null cells.niemann-pick disease type c (npc) is an autosomal recessive disorder characterized by abnormal accumulation of free cholesterol and sphingolipids in lysosomes. the iminosugar miglustat, which inhibits hexosylceramide synthesis, is used for npc treatment, and 2-hydroxypropyl-β-cyclodextrin (hp-β-cd), a cyclic oligosaccharide derivative, is being developed to treat npc. moreover, therapeutic potential of 2-hydroxypropyl-γ-cyclodextrin (hp-γ-cd) was shown in npc models, although its mechanism of ac ...202032019132
anti-d monoclonal antibodies from 23 human and rodent cell lines display diverse igg fc-glycosylation profiles that determine their clinical efficacy.anti-d immunoglobulin (anti-d ig) prophylaxis prevents haemolytic disease of the fetus and newborn. monoclonal igg anti-ds (mab-ds) would enable unlimited supplies but have differed in efficacy in fcγriiia-mediated adcc assays and clinical trials. structural variations of the oligosaccharide chains of mab-ds are hypothesised to be responsible. quantitative data on 12 fc-glycosylation features of 23 mab-ds (12 clones, 5 produced from multiple cell lines) and one blood donor-derived anti-d ig were ...202032001734
evaluation of glycoprotein e subunit and live attenuated varicella-zoster virus vaccines formulated with a single-strand rna-based adjuvant.varicella-zoster virus (vzv), a human alphaherpesvirus 3, elicits both chickenpox and shingles and/or postherpetic neuralgia. a live attenuated vaccine (lav) and glycoprotein e (ge) subunit vaccine were developed to prevent vzv-induced diseases. we recently reported that single-strand rna (ssrna) based on the intergenic region of the internal ribosome entry site of cricket paralysis virus (crpv) is an effective adjuvant for protein-based and virus-like particle-based vaccines. here, chinese hams ...202032167678
review of the current methods of chinese hamster ovary (cho) cells cultivation for production of therapeutic protein.most of clinical approved protein-based drugs or under in clinical trial have a profound impact in the treatment of critical diseases. the mammalian eukaryotic cells culture approaches, particularly the cho (chinese hamster ovary) cells are mainly used in the biopharmaceutical industry for the mass-production of therapeutic protein. recent advances in cho cell bioprocessing to yield recombinant proteins and monoclonal antibodies have enabled the expression of quality protein. the developments of ...202032164511
effects of titanium dioxide nanoparticles on the hprt gene mutations in v79 hamster cells.the genotoxicity of anatase/rutile tio2 nanoparticles (tio2 nps, nm105 at 3, 15 and 75 µg/cm2) was assessed with the mammalian in-vitro hypoxanthine guanine phosphoribosyl transferase (hprt) gene mutation test in chinese hamster lung (v79) fibroblasts after 24 h exposure. two dispersion procedures giving different size distribution and dispersion stability were used to investigate whether the effects of tio2 nps depend on the state of agglomeration. tio2 nps were fully characterised in the previ ...202032150818
antibody-drug conjugates using mouse-canine chimeric anti-dog podoplanin antibody exerts antitumor activity in a mouse xenograft model.antibody-drug conjugates (adcs), which consist of a monoclonal antibody (mab), a linker, and a payload, can deliver a drug to cancer tissues. we previously produced an anti-dog podoplanin (dpdpn) mab, pmab-38, which reacts with dpdpn-expressing canine melanomas and squamous cell carcinomas (sccs), but not with dpdpn-expressing canine type i alveolar cells or lymphatic endothelial cells, indicating that pmab-38 possesses cancer specificity. in this study, we developed an adc, p38b-dm1, using the ...202032182186
cell function profiling to assess clone stability.in cell line development the identification of stable chinese hamster ovary cells for production is a critical but onerous task. the stability trial focus upon high-level attributes can mask profound underlying cellular changes, leading to unstable clones mistakenly being chosen for production. the challenge is to assay underlying cell pathways and subsystems without pushing up cell line development costs. chemstress® cell function profiling is a simple, multiwell plate-based assay that uses a p ...202032181887
hydrocyclones as cell retention device for cho perfusion processes in single-use bioreactors.in this study, a hydrocyclone (hc) especially designed for mammalian cell separation was applied for the separation of chinese hamster ovary cells. the effect of key features on the separation efficiency, such as type of pumphead in the peristaltic feed pump, use of an auxiliary pump to control the perfusate flow rate, and tubing size in the recirculation loop were evaluated in batch separation tests. based on these preliminary batch tests, the hc was then integrated to 50-l disposable bioreacto ...202032181883
slowing of the time course of acidification decreases the acid-sensing ion channel 1a current amplitude and modulates action potential firing in neurons.acid-sensing ion channels (asics) are h+-activated neuronal na+ channels. they are involved in fear behavior, learning, neurodegeneration after ischemic stroke and in pain sensation. asic activation has so far been studied only with fast ph changes, although the ph changes associated with many roles of asics are slow. it is currently not known whether slow ph changes can open asics at all. here, we investigated to which extent slow ph changes can activate asic1a channels and induce action potent ...202032180707
multi-omics reveals impact of cysteine feed concentration and resulting redox imbalance on cellular energy metabolism and specific productivity in cho cell bioprocessing.chinese hamster ovary (cho) cells are currently the primary host cell lines used in biotherapeutic manufacturing of monoclonal antibodies (mabs) and other biopharmaceuticals. cellular energy metabolism and endoplasmic reticulum (er) stress are known to greatly impact cell growth, viability, and specific productivity of a biotherapeutic; but the molecular mechanisms are not fully understood. the authors previously employed multi-omics profiling to investigate the impact of a reduction in cysteine ...202032170810
enhancement of sialylation in rigg in glyco-engineered chinese hamster ovary cells.since about 70% of commercial biopharmaceutical products have been produced in chinese hamster ovary (cho) cells, this cell line is undeniably a workhorse for biopharmaceuticals production. meanwhile, sialic acid terminals were reported to affect anti-inflammatory activity, antibody-dependent cellular cytotoxicity efficacy of igg antibodies. taking these findings together, we aimed to establish cho cell lines that highly produce sialic acid terminals by overexpressing two n-acetylneuraminic acid ...202032125558
ascorbic acid 2-glucoside pretreatment protects cells from ionizing radiation, uvc, and short wavelength of uvb.ascorbic acid 2-glucoside (aa2g), glucosylated ascorbic acid (aa), has superior properties for bioavailability and stability compared to aa. although aa2g has shown radioprotective properties similar to aa, effects for uv light, especially uvc and uvb, are not studied. aa2g was tested for cytotoxicity and protective effects against ionizing radiation, uvc, and broadband and narrowband uvb in chinese hamster ovary (cho) cells and compared to aa and dimethyl sulfoxide (dmso). pretreatment with dms ...202032106443
understanding the effect of high gas entrance velocity on chinese hamster ovary (cho) cell culture performance and its implications on bioreactor scale-up and sparger design.there are three main potential sources for cell shear damage existing in stirred tank bioreactors. one is the potential high energy dissipation in the immediate impeller zones; another from small gas bubble burst; and third is from high gas entrance velocity (gev) emitting from the sparger. while the first two have been thoroughly addressed for the scale-up of chinese hamster ovary (cho) cell culture knowing that a wide tolerable agitation range with non-damaging energy dissipation exists and th ...202032086806
optimized crispr/cas9 strategy for homology-directed multiple targeted integration of transgenes in cho cells.site-specific integration has emerged as a promising strategy for precise chinese hamster ovary (cho) cell line engineering and predictable cell line development (cld). crispr/cas9 with the homology-directed repair (hdr) pathway enables precise integration of transgenes into target genomic sites. however, inherent recalcitrance to hdr-mediated targeted integration (ti) of transgenes results in low targeting efficiency, thus requiring a selection process to find a targeted integrant in cho cells. ...202032086804
identification and functional characterization of a novel splicing variant in the f8 coagulation gene causing severe hemophilia a.we have identified a synonymous f8 variation in a severe hemophilia a (ha) patient who developed inhibitors following factor viii (fviii) prophylaxis. the unreported c.6273 g > a variant targets the consensus splicing site of exon 21.202032078252
[eukaryotic expression, protein purification and biological effects research of human cs1-fc fusion protein].signaling lymphocyte activation family 7 (slamf7/cs1) is a cell surface glycoprotein that is highly expressed in multiple myeloma cells. cs1 is a sensitive and specific biomarker for multiple myeloma. car-t cell immunotherapy is a new method for the treatment of multiple myeloma. cs1 car-t cell immunotherapy has good effect on relapsed refractory multiple myeloma. to detect the expression efficiency of cs1 car on cs1 car-t cells and to find an auxiliary means to car-t cell immunotherapy, we prep ...202032072787
data for engineering lipid metabolism of chinese hamster ovary (cho) cells for enhanced recombinant protein production.the data presented in this article relates to the manuscript entitled 'engineering of chinese hamster ovary cell lipid metabolism results in an expanded er and enhanced recombinant biotherapeutic protein production', published in the journal metabolic engineering [1]. in the article here, we present data examining the overexpression of the lipid metabolism modifying genes scd1 and srebf1 in cho cells by densitometry of western blots and by using mass spectrometry to investigate the impact on spe ...202032071989
the use of catechins in chinese hamster ovary cell media for the improvement of monoclonal antibody yields and a reduction of acidic species.catechin compounds have potential benefits for recombinant monoclonal antibody (mab) production as chemical additives in cell culture media. in this study, four catechin compounds catechin (cat), epicatechin (ec), gallocatechin-gallate (gcg), and epigallocatechin-gallate (egcg) were added to cell culture media (at 50 μm) and their effects on the recombinant chinese hamster ovary (cho) cell culture, specific productivity, and mab quality were assessed. the results indicate that the improvement of ...202032067358
neutralizing antibody against osteopontin attenuates non-alcoholic steatohepatitis in mice.previously, we reported that an extracellular matrix protein, osteopontin (opn), is involved in various autoimmune diseases using a neutralizing polyclonal antibody against opn generated in rabbits. however, the antibody cannot be used for long-term mouse models of chronic inflammatory disease because of the induction of antibodies against anti-opn rabbit igg. in this study, we generated a new antibody, anti-mouse opn mouse igg (35b6). 35b6 inhibited the cell adhesion of mouse and human opn to c ...202032062834
codon and amino acid content are associated with mrna stability in mammalian cells.messenger rna (mrna) degradation plays a critical role in regulating transcript levels in the cell and is a major control point for modulating gene expression. in yeast and other model organisms, codon identity is a powerful determinant of transcript stability, contributing broadly to impact half-lives. general principles governing mrna stability are poorly understood in mammalian systems. importantly, however, the degradation machinery is highly conserved, thus it seems logical that mammalian t ...202032053646
single-step synthesis and in vitro anti-mycobacterial activity of novel nitrofurantoin analogues.the emergence of drug-resistant tuberculosis (dr-tb) as well as the requirement for long, expensive and toxic drug regimens impede efforts to control and eliminate tb. therefore, there's a need for effective and affordable anti-mycobacterial agents which can shorten the duration of therapy and are active against mycobacterium tuberculosis (mtb) in both active and latent phases. nitrofurantoin (nft) is a hypoxic agent with activity against a myriad of anaerobic pathogens and, like the first-line ...202032044516
protective effects of compounds from cimicifuga dahurica against amyloid beta production in vitro and scopolamine-induced memory impairment in vivo.cimicifuga dahurica has traditionally been used as an antipyretic, analgesic, and anti-inflammatory agent and as a treatment for uterine and anal prolapse. this study has investigated the potential beneficial effects of this medicinal plant and its components on alzheimer's disease (ad) with a focus on amyloid beta (aβ) production and scopolamine-induced memory impairment in mice. an ethanol extract from c. dahurica roots decreased aβ production in app-cho cells [chinese hamster ovarian (cho) ce ...202032031796
circulating ficolin-2 and ficolin-3 form heterocomplexes.the complement system constitutes an important part of the innate immune system. the collectins and the ficolins are soluble pattern recognition molecules that contribute to complement activation via the lectin pathway. during previous experiments with ficolin-2 and ficolin-3, we have observed that the molecules may interact. we therefore hypothesized the existence of stable ficolin-2/-3 heterocomplexes. we could demonstrate ficolin-2/-3 heterocomplexes in normal human serum and plasma by elisa ...202032094208
synthesis and biological evaluation of antibody drug conjugates based on an antibody expression system: conamax.antibody production for adcs (or in general) is commonly performed by cho-based platforms and limited by volumetric productivity, expensive downstream purification, and extended optimization timelines. the conamax platform is a novel microbial-based protein production and secretion system. a suite of synthetic biology tools have enabled high volumetric productivity (>1 g/l/d) and glycoengineering to produce simple and consistent human-like post-translational modifications. conamax can be enginee ...202032280859
safety evaluation of water extract of gastrodia elata blume: genotoxicity and 28-day oral toxicity studies.water extract of gastrodia elata blume (wge) has great potential as an anti-depressant and could be developed as a functional food. this study aims to assess the safety of wge using in vitro and in vivo genotoxicity assays and a 28-day oral toxicity study. results from a bacterial reverse mutation assay (ames test) using five salmonella typhimurium strains (ta98, ta100, ta102, ta1535, and ta1537) with or without metabolic activation (s9 system) showed that wge did not induce mutagenicity. nor di ...202032278877
temperature down-shift modifies expression of upr-/erad-related genes and enhances production of a chimeric fusion protein in cho cells.low culture temperature enhances the cell-specific productivity of chinese hamster ovary (cho) cells expressing varied recombinant (r-) proteins, but the mechanisms remain unclear. regulation of unfolded protein response (upr) pathway genes, such as transcriptional regulatory factors and endoplasmic reticulum (er)-resident proteins, appear to be involved in the improvements of r-protein production under low temperature conditions. the transcriptional regulation of upr-specific targets is studied ...202032271992
a proteomic approach towards understanding crypoprotective action of me2so on the cho cell proteome.chinese hamster ovary (cho) cell lines are the most widely used in vitro cells for research and production of recombinant proteins such as rhgh, tpa, and erythropoietin. we aimed to investigate changes in protein profiles after cryopreservation using 2d-dige maldi-tof ms and network pathway analysis. the proteome changes that occur in cho cells between freshly prepared cells and cryopreserved cells with and without me2so were compared to determine the key proteins and pathways altered during rec ...202032259523
comparison of a novel homogeneous cyclic amp assay and a luciferase assay for measuring stimulating thyrotropin-receptor autoantibodies.stimulating thyrotropin-receptor antibodies (tsab) cause graves' disease (gd). we tested a novel homogeneous fluorescent 3',5' cyclic adenine monophosphate (camp) assay for the detection of tsab in a bioassay.202032257955
antiarrhythmic mechanisms of chinese herbal medicine dingji fumai decoction.dingji fumai decoction (dfd) is used to treat ventricular arrhythmia, and it has provided a very good curative effect. however, its cellular electrophysiological mechanism is unknown.202032256664
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