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high-level expression of biologically active human follicle stimulating hormone in the chinese hamster ovary cell line by a pair of tricistronic and monocistronic vectors.recombinant human follicle stimulating hormone (fsh), produced in chinese hamster ovary (cho) cells, is widely used for treatment of fertility disorders and is subject to biosimilars development. cell lines with high specific productivities may simplify the fsh production process. here, we used our previously established expression system based on vector p1.1 to create new cell lines secreting heterodimeric fsh protein. to this end, we linked open reading frames of both fsh subunits by the wild- ...201931276557
novel promoters derived from chinese hamster ovary cells via in silico and in vitro analysis.for the industrial production of recombinant proteins in mammalian cell lines, a high rate of gene expression is desired. therefore, strong viral promoters are commonly used. however, these have several drawbacks as they override cellular responses, are not integrated into the cellular network, and thus can induce stress and potentially epigenetic silencing. endogenous promoters potentially have the advantage of a better response to cellular state and thus a lower stress level by uncontrolled ov ...201931271264
a high-throughput system for transient and stable protein production in mammalian cells.recombinant protein expression and purification is an essential component of biomedical research and drug discovery. advances in automation and laboratory robotics have enabled the development of highly parallel and rapid processes for cell culture and protein expression, purification, and analysis. human embryonic kidney (hek) cells and chinese hamster ovary (cho) cells have emerged as the standard host cell workhorses for producing recombinant secreted mammalian proteins by using both transien ...201931267450
involvement of renal efflux transporter mate1 in renal excretion of flecainide.flecainide, an anti-arrhythmic drug, undergoes renal excretion through active renal tubular secretion in addition to passive glomerular filtration. the contribution of renal uptake and efflux transporters in active renal tubular secretion of flecainide remains unclear except that flecainide is a substrate of human multidrug resistance protein 1 (mdr1). to elucidate renal efflux and uptake transporters involved with active renal tubular secretion of flecainide, we conducted in vitro interaction s ...201931257298
underestimated risk from ozonation of wastewater containing bromide: both organic byproducts and bromate contributed to the toxicity increase.ozonation is widely used in wastewater treatment but the associated byproduct formation is a concern. when ozonation is used in the presence of bromide, bromate is generally considered as a major byproduct, and few studies have examined the toxicity of organic byproducts. this study was designed to investigate the cytotoxicity, genotoxicity and dna/rna oxidative damage to chinese hamster ovary (cho) cells of organic extracts from ozonated wastewater in the absence or presence of bromide. ozonati ...201931254885
inhibition of neutral lipid synthesis by avarols from a marine sponge.the effects of 14 sesquiterpene hydroquinones, including 8 marine sponge-derived avarols (1-8) and 6 semisynthetic derivatives (9-14), on lipid droplet accumulation and neutral lipid synthesis in chinese hamster ovary (cho) k1 cells were investigated. in intact cho-k1 cell assays, avarol (1) markedly decreased the number and size of lipid droplets in cho-k1 cells and exhibited the most potent inhibitory activity on the synthesis of cholesteryl ester (ce) and triglyceride (tg) with ic50 values of ...201931253530
application of mie theory for enhanced size determination of microparticles using optical particle counters.the approach to particle sizing with optical particle counters is often simple interpolation of calibration data. a method is presented that uses the results of mie-theory-based simulations to describe the signal between calibration points, thus reducing the number of necessary calibration points or increasing the sizing accuracy significantly. through the use of mie theory, particles with a refractive index differing from the calibration particles can be measured without an individual calibrati ...201931251277
genetic engineering approaches to improve posttranslational modification of biopharmaceuticals in different production platforms.the number of approved biopharmaceuticals, where product quality attributes remain of major importance, is increasing steadily. within the available variety of expression hosts, the production of biopharmaceuticals faces diverse limitations with respect to posttranslational modifications (ptm), while different biopharmaceuticals demand different forms and specifications of ptms for proper functionality. with the growing toolbox of genetic engineering technologies, it is now possible to address g ...201931237682
role of network-mediated stochasticity in mammalian drug resistance.a major challenge in biology is that genetically identical cells in the same environment can display gene expression stochasticity (noise), which contributes to bet-hedging, drug tolerance, and cell-fate switching. the magnitude and timescales of stochastic fluctuations can depend on the gene regulatory network. currently, it is unclear how gene expression noise of specific networks impacts the evolution of drug resistance in mammalian cells. answering this question requires adjusting network no ...201931235692
chemical synthesis, proper folding, nav channel selectivity profile and analgesic properties of the spider peptide phlotoxin 1.phlotoxin-1 (phltx1) is a peptide previously identified in tarantula venom (phlogius species) that belongs to the inhibitory cysteine-knot (ick) toxin family. like many ick-based spider toxins, the synthesis of phltx1 appears particularly challenging, mostly for obtaining appropriate folding and concomitant suitable disulfide bridge formation. herein, we describe a procedure for the chemical synthesis and the directed sequential disulfide bridge formation of phltx1 that allows for a straightforw ...201931234412
identification and characterization of co-purifying cho host cell proteins in monoclonal antibody purification process.host cell proteins (hcps) are process-related impurities derived from the host organism such as chinese hamster ovary (cho) cells used for the production of therapeutic mabs in biopharmaceuticals and potentially pose a risk to patient safety and product efficacy. a number of hcps have been reported as exceptionally difficult to remove and persist across downstream purification operations into final drug product because they exhibit association with mabs. therefore, understanding of hcp impuritie ...201931234041
[increasing transgenic expression in recombinant chinese hamster ovary cells using introns in different directions].the aim of this study is to investigate the effect of the chimeric intron in different directions on the expression of the nerve growth factor (ngf) in recombinant chinese hamster ovary (cho) cells. the chimeric intron that contained the splice sequence of the first intron of the human β-globin and the human immunoglobulin heavy chain variable region intron was used. ngf gene was cloned into the expression vectors containing the chimeric intron in the forward or reverse direction, followed by tr ...201931232003
dna retention on depth filters.depth filtration is a commonly-used bioprocessing unit operation for harvest clarification that reduces the levels of process- and product-related impurities such as cell debris, host-cell proteins, nucleic acids and protein aggregates. since depth filters comprise multiple components, different functionalities may contribute to such retention, making the mechanisms by which different impurities are removed difficult to decouple. here we probe the mechanisms by which double-stranded dna (dsdna) ...201931223185
sniffer cells for the detection of neural angiotensin ii in vitro.neuropeptide release in the brain has traditionally been difficult to observe. existing methods lack temporal and spatial resolution that is consistent with the function and size of neurons. we use cultured "sniffer cells" to improve the temporal and spatial resolution of observing neuropeptide release. sniffer cells were created by stably transfecting chinese hamster ovary (cho) cells with plasmids encoding the rat angiotensin type 1a receptor and a genetically encoded ca2+ sensor. isolated, cu ...201931217439
design and use of chikungunya virus replication templates utilizing mammalian and mosquito rna polymerase i-mediated transcription.chikungunya virus (chikv) is a mosquito-borne alphavirus. it has a positive-sense rna genome that also serves as the mrna for four nonstructural proteins (nsps) representing subunits of the viral replicase. coupling of nsp and rna synthesis complicates analysis of viral rna replication. we developed trans-replication systems, where production of replication-competent rna and expression of viral replicase are uncoupled. mammalian and mosquito rna polymerase i promoters were used to produce noncap ...201931217251
a cross-species whole genome sirna screen in suspension-cultured chinese hamster ovary cells identifies novel engineering targets.high-throughput sirna screens were only recently applied to cell factories to identify novel engineering targets which are able to boost cells towards desired phenotypes. while sirna libraries exist for model organisms such as mice, no cho-specific library is publicly available, hindering the application of this technique to cho cells. the optimization of these cells is of special interest, as they are the main host for the production of therapeutic proteins. here, we performed a cross-species a ...201931213643
probing deviation of adhered membrane dynamics between reconstituted liposome and cellular system.the dynamics of cell-cell adhesion are complicated due to complexities in cellular interactions and intra-membrane interactions. in the present work, we have reconstituted a liposome-based model system to mimic the cell-cell adhesion process. our model liposome system consists of one fluorescein-tagged and one tritc (tetramethyl-rhodamine isothiocyanate)-tagged liposome, adhered through biotin-neutravidin interaction. we monitored the adhesion process in liposomes using förster resonance energy ...201931210021
bip inducer x: an er stress inhibitor for enhancing recombinant antibody production in cho cell culture.prolonged endoplasmic reticulum (er) stress reduces protein synthesis and induces apoptosis in mammalian cells. when dimethyl sulfoxide (dmso), a specific monoclonal antibody productivity (qmab )-enhancing reagent, is added to recombinant chinese hamster ovary (rcho) cell cultures (gsr cell line), it induces er stress and apoptosis in a dose-dependent manner. to determine an effective er stress inhibitor, three er stress inhibitors (bip inducer x [bix], tauroursodeoxycholic acid, and carbazole) ...201931161665
development of an improved lentiviral based vector system for the stable expression of monoclonal antibody in cho cells.therapeutic monoclonal antibodies (mabs) have become the dominant products in biopharmaceutical industry. mammalian cell expression systems including chinese hamster ovary (cho) cells are the most commonly used hosts for the production of complex recombinant proteins. however, development of stable, high producing cho cell lines suffers from the low expression level and instability of the transgene. the increasing efforts in the development of novel therapeutic antibodies and the advent of biosi ...201931156045
cation exchange chromatography performed in overloaded mode is effective in removing viruses during the manufacturing of monoclonal antibodies.viral safety is a critical concern with regard to monoclonal antibody (mab) products produced in mammalian cells such as chinese hamster ovary cells. manufacturers are required to ensure the safety of such products by validating the clearance of viruses in downstream purification steps. cation exchange (cex) chromatography is widely used in bind/elute mode as a polishing step in mab purification. however, bind/elute modes require a large volume of expensive resin. to reduce the production cost, ...201931148380
superfluous glutamine synthetase activity in chinese hamster ovary cells selected under glutamine limitation is growth limiting in glutamine-replete conditions and can be inhibited by serine.passaging and expansion of animal cells in lean maintenance medium could result in periods of limitation of some nutrients. over time, such stresses could possibly result in selection of cells with metabolic changes and contribute to heterogeneity. here, we investigate whether selection of chinese hamster ovary (cho) cells under glutamine limitation results in changes in growth under glutamine-replete conditions. in glutamine-limiting medium, compared to control cells passaged in glutamine-rich ...201931148368
immune persistence 17 to 20 years after primary vaccination with recombination hepatitis b vaccine (cho) and the effect of booster dose vaccination.to assess the immune persistence conferred by a chinese hamster ovary (cho)-derived hepatitis b vaccine (hepb) 17 to 20 years after primary immunization during early life.201931146699
precision of scoring radiation-induced chromosomal aberrations and micronuclei by unexperienced scorers.purpose: dose assessment plays an important role in case of radiological accidents and can be performed by scoring structural changes of chromosome morphology induced in cells by ionizing radiation. the results of such a test are biased by scorer experience, therefore, simple to learn assays are recommended to be used when fast analysis of a large amount of data is needed. the aim of this study was to compare the performance of two radiobiological assays - chromosomal aberrations and micronuclei ...201931140900
oxidative stress and endoreduplication induced by blue light exposure to cho cells.blue light is commonly used for the treatment of neonatal jaundice and as a photodynamic therapy for cancer. in comparison to ultraviolet light, blue light has a lower toxicity due to the differences in photon energies. however, blue light can still be mutagenic to cells. the proposed mechanism suggests blue light exposure induces reactive oxygen species inducing oxidative stress. in this study, we examined how blue light exposure caused genotoxic effects utilizing chinese hamster ovary (cho) ce ...201931138408
evaluation of a single amino acid substitution at position 79 of human ifn-α2b in interferon-receptor assembly and activity.type i interferons (ifns) are homologous cytokines that bind to a cell surface receptor and establish signaling pathways that motivate immune responses. the purpose of the current study is to assess the activity of a novel-engineered ifn-α2b. the crystallographic structure of ifn-α2b and its receptors was acquired from protein data bank. various amino acid substitutions were designed based on structural properties and other biological characteristics of residues to find the most effective amino ...201931135267
comparative toxicity study of a novel non-ionic surfactant, vanillin ethoxylates, and nonylphenol ethoxylates in chinese hamster ovary cells in vitro.surfactants such as alkylphenol polyethoxylates (apeos) and nonylphenol ethoxylates (npeos) are commonly used worldwide, but the majority of these compounds, together with their metabolites, have been reported to induce severe biological toxicity. here, we evaluated for the first time the cytotoxicity, genotoxicity and mitochondrial damage in chinese hamster ovary (cho-k1) cells caused by a novel non-ionic surfactant, vanillin ethoxylates (vaeos), an alternative to apeos. in parallel, the same i ...201931133271
photochemical oxidation of ppcps using a combination of solar irradiation and free available chlorine.the degradation of pharmaceuticals and personal care products (ppcps) by using solar photolysis in the presence of free available chlorine (fac) was investigated in simulated drinking water. the combination of free available chlorine and sunlight irradiation dramatically accelerated the degradation of all the contaminants tested through the generation of hydroxyl radicals, reactive chlorine species (rcs) and ozone. contaminants containing electron-donating moieties degraded quickly and were pref ...201931129545
a flipr assay for discovery of gabaa receptor modulators of natural origin.a fluorometric imaging plate reader (flipr) assay utilizing chinese hamster ovary (cho) cells stably transfected with gabaa receptors of α1β2γ2 subunit composition was evaluated and validated for rapid screening of plant extract libraries and efficient localization of active compounds in extracts. validation was performed with pure compounds and extracts known to contain allosteric gabaa receptor modulators. plants extracts that had been previously reported as active in an assay using xenopus la ...201931127604
in vitro cytotoxicity studies of industrial eucalyptus kraft lignins on mouse hepatoma, melanoma and chinese hamster ovary cells.kraft lignin is a polyphenolic compound generated as a by-product from the kraft pulping process in large quantities annually worldwide. in addition to its commercial availability, its structural features make it worth to be considered in the pharmaceutical area. the present study was carried out to evaluate in vitro antioxidant and cytotoxic properties of kraft lignin on mouse hepatoma mh-22a, melanoma b16 (tumor cells) and chinese hamster ovary (cho, non-cancerous) cells. moreover, several ana ...201931125648
application of er stress biomarkers to predict formulated monoclonal antibody stability.for a therapeutic monoclonal antibody (mab) to reach the clinic, the molecule must be produced at an appropriate yield and quality, then formulated to maintain efficacy and stability. the formation of subvisible particles (svps) can impact product stability and is monitored during formulation development; however, the potential of a mab to form such species can be influenced throughout the whole bioprocess. the levels of intracellular endoplasmic reticulum (er) stress perceived by chinese hamste ...201931119893
multiple conserved elements structuring inverted repeats in the mammalian coat color-related gene asip.in the agouti signaling gene protein (asip) of the house mouse (mus musculus), inverted repeat (ir) arrays are known to exist in a non-coding region adjacent to the ventral-specific promoter region and the accompanying two exons (exons 1a and 1a'), which are around 100 kb upstream from the amino acid coding regions of exons 2, 3, and 4. to determine the gene structure of mammalian asip and to elucidate trends in its evolution, non-coding sequences of six rodent (mouse, rat, chinese hamster, squi ...201931116535
improvement of growth rates through nucleoside media supplementation of cho clones.chinese hamster ovary (cho) cells are used for the production of therapeutic proteins. this work examines improving passaging growth rate of two cho clones. growth rates were significantly improved for both clones with supplementation of the nucleosides cytidine, hypoxanthine, uridine, and thymidine to the culturing media at the optimal concentration of 100 µm of each nucleoside. we investigated supplementing the same combination of nucleosides to seed bioreactors and production fed batch biorea ...201931115721
improved recombinant protein production by regulation of transcription and protein transport in chinese hamster ovary cells.to identify genes that affected protein expression in chinese hamster ovary (cho) cells was significant, and we identified the changes in the transcriptome and the functional gene sets that would contribute to increase expression of recombinant protein.201931114947
small-molecule control of antibody n-glycosylation in engineered mammalian cells.n-linked glycosylation in monoclonal antibodies (mabs) is crucial for structural and functional properties of mab therapeutics, including stability, pharmacokinetics, safety and clinical efficacy. the biopharmaceutical industry currently lacks tools to precisely control n-glycosylation levels during mab production. in this study, we engineered chinese hamster ovary cells with synthetic genetic circuits to tune n-glycosylation of a stably expressed igg. we knocked out two key glycosyltransferase ...201931110306
purification and analytics of a monoclonal antibody from chinese hamster ovary cells using an automated microbioreactor system.monoclonal antibodies (mabs) are one of the most popular and well-characterized biological products manufactured today. most commonly produced using chinese hamster ovary (cho) cells, culture and process conditions must be optimized to maximize antibody titers and achieve target quality profiles. typically, this optimization uses automated microscale bioreactors (15 ml) to screen multiple process conditions in parallel. optimization criteria include culture performance and the critical quality a ...201931107445
ca2+ signal is involved in endothelin-1-induced internalization of endothelin type a receptor expressed in chinese hamster ovary cells.endothelin type a receptor (etar) is internalized upon agonist stimulation; however, the mechanism thereof remains controversial. in this study, we characterized the endothelin-1 (et-1)-induced internalization of etar expressed in chinese hamster ovary cells. et-1 elicited etar internalization and increase in intracellular ca2+ concentration. et-1-induced etar internalization was completely inhibited by a reduction in intracellular and extracellular ca2+ levels and partially suppressed by inhibi ...201931103330
comparative toxicity of organic mixture attached to road deposited sediments: inadequacy of conventionally using individual pollutants to assess comprehensive hazard effects.organic pollutants attached on road deposited sediments (rds) during dry days can be washed-off into stormwater runoff during rainfall events, undermining stormwater reuse safety. previous research studies commonly utilized individual pollutant groups and their quantity to evaluate the hazard effect of pollutants attached to rds in terms of stormwater reuse. since many types of organic pollutants are present together rather than individually, conventional approaches might not permit a comprehens ...201931102843
limiting the metabolic burden of recombinant protein expression during selection yields pools with higher expression levels.in order to avoid the metabolic burden of protein expression during cell growth, and to avoid potential toxicity of recombinant proteins, microbial expression systems typically utilize regulated expression vectors. in contrast, constitutive expression vectors have usually been utilized for isolation of protein expressing mammalian cell lines. in mammalian systems, inducible expression vectors are typically utilized for only those proteins that are toxic when overexpressed. we developed a tetracy ...201931090257
identification and crispr/cas9 inactivation of the c1s protease responsible for proteolysis of recombinant proteins produced in cho cells.proteolysis associated with recombinant protein expression in chinese hamster ovary (cho) cells has hindered the development of biologics including hiv vaccines. when expressed in cho cells, the recombinant hiv envelope protein, gp120, undergoes proteolytic clipping by a serine protease at a key epitope recognized by neutralizing antibodies. the problem is particularly acute for envelope proteins from clade b viruses that represent the major genetic subtype circulating in much of the developed w ...201931087560
bell-shaped agonist activation of 5-ht1a receptor-coupled gαi3 g-proteins: receptor density-dependent switch in receptor signaling.a previous study observed bell-shaped concentration-response isotherms for activation of gαi3 g-protein subunits by high efficacy 5-ht1a receptor agonists in a chinese hamster ovary (cho) cell line expressing high levels of these receptors. this suggested that a signaling switch took place in that cell line (from gαi3 to activation of other g-proteins) but it was unclear if such effects are observed for 5-ht1a receptors in other cellular environments. here, using an antibody capture-based [35s]g ...201931376526
clostridium perfringens epsilon toxin vaccine candidate lacking toxicity to cells expressing myelin and lymphocyte protein.a variant form of clostridium perfringens epsilon toxin (y30a-y196a) with mutations, which shows reduced binding to madin-darby canine kidney (mdck) cells and reduced toxicity in mice, has been proposed as the next-generation enterotoxaemia vaccine. here we show that, unexpectedly, the y30a-y196a variant does not show a reduction in toxicity towards chinese hamster ovary (cho) cells engineered to express the putative receptor for the toxin (myelin and lymphocyte protein; mal). the further additi ...201931372245
exploring the n-glycosylation profile of glycoprotein b from human cytomegalovirus expressed in cho and nicotiana tabacum by-2 cells.the ability to control the glycosylation pattern of recombinant viral glycoproteins represents a major prerequisite before their use as vaccines. the aim of this study consisted of expressing the large soluble ectodomain of glycoprotein b (gb) from human cytomegalovirus (hmcv) in nicotiana tabacum bright yellow-2 (by-2) suspension cells and of comparing its glycosylation profile with that of gb produced in chinese hamster ovary (cho) cells. gb was secreted in the by-2 culture medium at a concent ...201931370181
cellular targeting of bispecific antibody-functionalized poly(ethylene glycol) capsules: do shape and size matter?in the present study, a capsule system that consists of a stealth carrier based on poly(ethylene glycol) (peg) and functionalized with bispecific antibodies (bsabs) is introduced to examine the influence of the capsule shape and size on cellular targeting. hollow spherical and rod-shaped peg capsules with tunable aspect ratios (ars) of 1, 7, and 18 were synthesized and subsequently functionalized with bsabs that exhibit dual specificities to peg and epidermal growth factor receptor (egfr). dosim ...201931369234
gut microbial metabolites of linoleic acid are metabolized by accelerated peroxisomal β-oxidation in mammalian cells.microorganisms in animal gut produce unusual fatty acids from the ingested diet. two types of hydroxy fatty acids (hfas), 10-hydroxy-cis-12-octadecenoic acid (hya) and 10-hydroxy-octadecanoic acid (hyb), are linoleic acid (la) metabolites produced by lactobacillus plantarum. in this study, we investigated the metabolism of these hfas in mammalian cells. when chinese hamster ovary (cho) cells were cultured with hya, approximately 50% of the supplemented hya disappeared from the dish within 24 h. ...201931351225
germinality does not necessarily define mab expression and thermal stability.the production potential of recombinant monoclonal antibody (mab) expressing cell lines depends, among other factors, on the intrinsic antibody structure determined by the amino acid sequence. in this study, we investigated the influence of somatic mutations in the v(d)j sequence of four individual, mature model mabs on the expression potential. therefore, we defined four couples, each consisting of one naturally occurring mab (2g12, ustekinumab, 4b3, and 2f5) and the corresponding germline-deri ...201931350616
predicting industrial-scale cell culture seed trains-a bayesian framework for model fitting and parameter estimation, dealing with uncertainty in measurements and model parameters, applied to a nonlinear kinetic cell culture model, using an mcmc method.for production of biopharmaceuticals in suspension cell culture, seed trains are required to increase cell number from cell thawing up to production scale. because cultivation conditions during the seed train have a significant impact on cell performance in production scale, seed train design, monitoring, and development of optimization strategies is important. this can be facilitated by model-assisted prediction methods, whereby the performance depends on the prediction accuracy, which can be i ...201931347693
an unconventional uptake rate objective function approach enhances applicability of genome-scale models for mammalian cells.constraint-based modeling has been applied to analyze metabolism of numerous organisms via flux balance analysis and genome-scale metabolic models, including mammalian cells such as the chinese hamster ovary (cho) cells-the principal cell factory platform for therapeutic protein production. unfortunately, the application of genome-scale model methodologies using the conventional biomass objective function is challenged by the presence of overly-restrictive constraints, including essential amino ...201931341637
pmab-235: a monoclonal antibody for immunohistochemical analysis against goat podoplanin.sensitive and specific monoclonal antibodies (mabs) against not only human but also mouse, rat, rabbit, dog, cat, bovine, pig, and horse podoplanins (pdpns) have been established in our previous studies. however, anti-goat pdpn (gpdpn) has not been established yet. pdpn has been utilized as a lymphatic endothelial cell marker especially in pathological diagnoses; therefore, mabs for immunohistochemical analyses using formalin-fixed paraffin-embedded tissues are needed. although we recently demon ...201931338471
fabrication of amyloid-β-secreting alginate microbeads for use in modelling alzheimer's disease.according to the amyloid cascade hypothesis, the earliest trigger in the development of alzheimer's disease (ad) is the accumulation of toxic amyloid-β (aβ) fragments, eventually leading to the classical features of the disease: amyloid plaques, neurofibrillary tangles and synaptic and neuronal loss. the lack of relevant non-transgenic preclinical models reflective of disease progression is one of the main factors hindering the discovery of effective drug treatments. to this end, we have develop ...201931329175
egf receptor stalls upon activation as evidenced by complementary fluorescence correlation spectroscopy and fluorescence recovery after photobleaching measurements.to elucidate the molecular details of the activation-associated clustering of epidermal growth factor receptors (egfrs), the time course of the mobility and aggregation states of egfp tagged egfr in the membranes of chinese hamster ovary (cho) cells was assessed by in situ mobility assays. fluorescence correlation spectroscopy (fcs) was used to probe molecular movements of small ensembles of molecules over short distances and time scales, and to report on the state of aggregation. the diffusion ...201931323980
activin a-induced cachectic wasting is attenuated by systemic delivery of its cognate propeptide in male mice.in cancer, elevated activin levels promote cachectic wasting of muscle, irrespective of tumor progression. in excess, activins a and b use the myostatin signaling pathway in muscle, triggering a decrease in protein synthesis and an increase in protein degradation, which ultimately leads to atrophy. recently, we demonstrated that local delivery of engineered activin and myostatin propeptides (natural inhibitors of these growth factors) could induce profound muscle hypertrophy in healthy mice. add ...201931322699
influence of environmental conditions on the fusion of cationic liposomes with living mammalian cells.lipid-based nanoparticles, also called vesicles or liposomes, can be used as carriers for drugs or many types of biological macromolecules, including dna and proteins. efficiency and speed of cargo delivery are especially high for carrier vesicles that fuse with the cellular plasma membrane. this occurs for lipid mixture containing equal amounts of the cationic lipid dotap and a neutral lipid with an additional few percents of an aromatic substance. the fusion ability of such particles depends o ...201931319557
expression, purification, and characterization of a human complement component c3 analog that lacks the c-terminal c345c domain.the complement system consists of a series of soluble and cell-surface proteins that serve numerous roles in innate immunity, development, and homeostasis. despite its many functions, the central event in the complement system is the proteolytic activation of the 185 kda complement component 3 (c3) into its opsonin and anaphylatoxin fragments known as c3b (175 kda) and c3a (10 kda), respectively. the c3 protein is comprised of thirteen separate structural domains, several of which undergo extens ...201931319063
coexpression of cmp-sialic acid transporter reduces n-glycolylneuraminic acid levels of recombinant glycoproteins in chinese hamster ovary cells.recombinant glycoproteins expressed in chinese hamster ovary (cho) cells contain two forms of sialic acids; n-acetylneuraminic acid (neu5ac) as a major type and n-glycolylneuraminic acid (neu5gc) as a minor type. the neu5gc glycan moieties in therapeutic glycoproteins can elicit immune responses because they do not exist in human. in the present work, to reduce neu5gc levels of recombinant glycoproteins from cho cell cultures, we coexpressed cytidine-5'-monophosphate-sialic acid transporter (cmp ...201931317538
glyconanoparticles for targeted tumor therapy of platinum anticancer drug.an important requirement to decrease the side effects of chemotherapy drugs is to develop nanocarriers with precise biological functions. in this work, a set of glyconanoparticles was prepared via self-assembly of amphiphilic glycoblock copolymers for the targeted delivery of a hydrophobic chemotherapy drug. well-defined glycoblock copolymers that consist of 1,1-di-tert-butyl 3-(2-(metyloyloxy)ethyl)-butane-1,1,3-tricarboxylate (maetc) together with three different protected-sugar moieties (β-d- ...201931314508
kinetic basis of metformin-mpp interactions with organic cation transporter oct2.organic cation transporter 2 (oct2) clears the blood of cationic drugs. efforts to understand oct2 selectivity as a means to predict the potential of new molecular entities (nmes) to produce unwanted drug-drug interactions typically assess the influence of the nmes on inhibition of transport. however, the identity of the substrate used to assess transport activity can influence the quantitative profile of inhibition. metformin and 1-methyl-4-phenylpyridinium (mpp), in particular, display markedl ...201931313952
bcat1 and bcat2 disruption in cho cells has cell line-dependent effects.in recombinant protein expression using chinese hamster ovary (cho) cells, chemically defined media contain essential amino acids such as branched chain amino acids (bcaas) leucine, isoleucine and valine. availability of amino acids is critical as these are building blocks for protein synthesis. however, breakdown of amino acids can lead to build up of toxic intermediates and metabolites that decrease cell growth, productivity and product quality. bcaa catabolism also hampers the usage of bcaas ...201931465797
novel single-chain variant of antibody against mesothelin established by phage library.mesothelin (msln) shows increased expression in various cancer cells. for clinical application of antibodies as a positron emission tomography (pet) imaging reagent, a human shortened antibody is essential both for avoiding redundant immune responses and for providing rapid imaging. therefore, we cloned a single-chain fragment of variable regions (scfv) from a human-derived gene sequence. this was achieved through the construction of a naïve phage library derived from human tonsil lymphocytes. u ...201931461572
rapid characterization of herg channel kinetics ii: temperature dependence.ion channel behavior can depend strongly on temperature, with faster kinetics at physiological temperatures leading to considerable changes in currents relative to room temperature. these temperature-dependent changes in voltage-dependent ion channel kinetics (rates of opening, closing, inactivating, and recovery) are commonly represented with q10 coefficients or an eyring relationship. in this article, we assess the validity of these representations by characterizing channel kinetics at multipl ...201931451180
rapid characterization of herg channel kinetics i: using an automated high-throughput system.predicting how pharmaceuticals may affect heart rhythm is a crucial step in drug development and requires a deep understanding of a compound's action on ion channels. in vitro herg channel current recordings are an important step in evaluating the proarrhythmic potential of small molecules and are now routinely performed using automated high-throughput patch-clamp platforms. these machines can execute traditional voltage-clamp protocols aimed at specific gating processes, but the array of protoc ...201931447109
comparing two automated high throughput viable-cell counting systems for cell culture applications.cell counting and viability assessment is an integral part of mammalian cell line development. while manual counting with a hemocytometer is still the gold standard method, its subjectivity and high labor intensity has resulted in its reduced use in favor of automated systems. in addition, some of these automated systems offer multiwell plate based high throughput cell count, which is an asset for biopharmaceutical companies generating hundreds of high-performance cell lines per year. in this st ...201931442502
cathepsin d: removal strategy on protein a chromatography, near real time monitoring and characterisation during monoclonal antibody production.monoclonal antibody (mab) fragmentation is a well-known degradation pathway that results in product loss and can significantly impact product quality, efficacy, or even cause immunogenic reactions, thus potentially endangering patients' health. it is recognised that residual proteases present among host cell proteins (hcps) such as those expressed by chinese hamster ovary (cho) can induce fragmentation, and failure of their complete removal during downstream processing could cause fragmentation ...201931442501
functional and structural characterization of hspb1/hsp27 from chinese hamster ovary cells.small heat shock proteins (shsps) endow cells with stress tolerance. of the various shsps in mammals, hspb1, also known as hsp27, is the most ubiquitous. to examine the structure and function of hspb1, we expressed, purified, and characterized hspb1 from chinese hamster (cricetulus griseus) ovary cells (cghspb1). cghspb1 forms a large oligomeric structure. we observed a monodisperse 16-mer with an elongated sphere, but this is affected by changes in various conditions, including temperature. und ...201931441240
gatifloxacin-1,2,3-triazole-isatin hybrids and their antimycobacterial activities.a series of gatifloxacin-1,2,3-triazole-isatin hybrids 8a-l were designed, synthesized, and screened for their in vitro antimycobacterial activity as well as cytotoxicity toward chinese hamster ovary (cho) cells. the synthesized hybrids showed considerable activity against mtb h37 rv and two mdr-mtb strains with minimal inhibitory concentration (mic) of 0.25-8 μg/ml, and the hybrid 8a (micmtb h37rv : 0.25 μg/ml and micmdr-mtb : 0.5 and 1 μg/ml) was found to be most active against the tested stra ...201931441087
genotoxicity and glucose tolerance induction by acetyltriethylcitrate, substitute plasticizer compared to di(2-ethylhexyl)phthalate.as di(2-ethylhexyl) phthalate (dehp), one of phthalates, is classified as probable human carcinogens in epa, acetyltriethyl citrate(atec), one of aliphatic esters, could be applied to dehp substitute. atec is used as plasticizers in cosmetics and nail products. here, we studied whether atec might have genotoxic potential and induce glucose tolerance as compared to dehp. genotoxicity was determined by ames test with histidine-requiring salmonella typhimurium (ta98, ta100, ta1535 and ta1537) and t ...201931439862
structure-activity relationship study: mechanism of cyto-genotoxicity of nitropyrazole-derived high energy density materials family.stringent toxicological tests have to be performed prior to the industrial development of alternative chemicals particularly high energy dense materials (hedms) such as explosives. the properties (e.g., power, stability) of these compounds are constantly being improved, the current axis of research being the nitration of nitrogen heterocycles leading to hedms such as nitropyrazole-derived molecules. however, except for 3,4,5-trinitropyrazole (3,4,5-tnp), which was shown to be highly toxic in mic ...201931437493
volatile organic compound (voc) emissions of cho and t cells correlate to their expansion in bioreactors.volatile organic compound (voc) emissions were measured from chinese hamster ovary (cho) cell and t cell bioreactor gas exhaust lines with the goal of non-invasively metabolically profiling the expansion process. measurements of cellular 'breath' were made directly from the gas exhaust lines using polydimethylsiloxane (pdms)-coated magnetic stir bars, which underwent subsequent thermal desorption-gas chromatography-mass spectrometry (td-gc-ms) analysis. baseline voc profiles were observed from b ...201931430743
a negative feedback loop regulates integrin inactivation and promotes neutrophil recruitment to inflammatory sites.neutrophils are abundant circulating leukocytes that are rapidly recruited to sites of inflammation in an integrin-dependent fashion. contrasting with the well-characterized regulation of integrin activation, mechanisms regulating integrin inactivation remain largely obscure. using mouse neutrophils, we demonstrate in this study that the gtpase activating protein arap3 is a critical regulator of integrin inactivation; experiments with chinese hamster ovary cells indicate that this is not restric ...201931427445
safety evaluation of pq birch allergy immunotherapy to support product development.pq birch represents an allergen-specific immunotherapy for the treatment of birch pollinosis. it consists of native birch pollen extract chemically modified with glutaldehyde adsorbed to l-tyrosine in its microcrystalline form with addition of the adjuvant monophosphoryl lipid a (mpl®). a nonclinical safety testing strategy was designed based upon interpretation of current legislation and regulatory intelligence and comprised genotoxicity studies (bacterial reverse mutation and chinese hamster o ...201931425728
uveitis sarcoidosis presumably initiated after administration of shingrix vaccine.uveitis is a form of intraocular inflammation that can occur as a result of infection, injury, vaccination, or as a systemic manifestation of autoimmune or inflammatory diseases including sarcoidosis. sarcoidosis is an inflammatory disease that involves the formation of abnormal granulomas in multiple organ systems. the hallmark of sarcoidosis is a non-caseating granuloma seen on biopsy. here, we present a case report of a healthy 56-year-old caucasian female who presented with uveitis sarcoidos ...201931423396
a comparison of the oligosaccharide structures of antithrombin derived from plasma and recombinant using potelligent® technology.human antithrombin (at) has two isoforms of which the predominant α-form is glycosylated on all four possible glycosylation sites and the lower abundant β-isoform lacks the oligosaccharide on asn135. the main oligosaccharide structure of human at consists of biantennary complex-type oligosaccharides lacking a core fucose. generally, chinese hamster ovary (cho) cells produce recombinant human at (rhat) with core-fucosylated oligosaccharides. however, rhat lacking core-fucose oligosaccharides can ...201931423004
clonal variations in cho igf signaling investigated by silac-based phosphoproteomics and lfq-ms.chinese hamster ovary (cho) cells are commonly used for the production of monoclonal antibodies. omics technologies have been used to elucidate cellular switch points which result in higher monoclonal antibody (mab) productivity and process yields in cho and other biopharmaceutical production cell lines such as human or mouse. currently, investigations of the phosphoproteome in cho cell lines are rare yet could provide further insights into cellular mechanisms related to target product expressio ...201931420692
enhanced transient expression of an anti-cd52 monoclonal antibody in cho cells through utilization of mirna sponge technology.chinese hamster ovary (cho) cells are the dominant mammalian host system for the production of recombinant therapeutic proteins. improving the viable cell density during culture of recombinant cho cells can greatly affect the production yield. micrornas (mirs) -15a and 16-1 are known as negative regulators of multiple genes involved in cell cycle progression and apoptotic inhibition. mir sponges, which act as decoy targets, are transcripts which contain complementary binding sites to the seed re ...201931516510
trehalose uptake and dehydration effects on the cryoprotection of cho-k1 cells expressing tret1.chinese hamster ovary cells (cho-k1 cells) in which the trehalose transporter (tret1) is expressed can have greater cryoprotection than ordinary cho-k1 cells. this study examines the uptake characteristics of trehalose into cells via tret1 and determines the influence of intracellular trehalose on the freeze-thaw viabilities. in our experiments, the intracellular trehalose concentration is controlled by the extracellular trehalose concentration and the immersion time in a freezing solution. in t ...201931499026
mitochondria supply atp to the er through a mechanism antagonized by cytosolic ca2.the endoplasmic reticulum (er) imports atp and uses energy from atp hydrolysis for protein folding and trafficking. however, little is known about how this vital atp transport occurs across the er membrane. here, using three commonly used cell lines (cho, ins1 and hela), we report that atp enters the er lumen through a cytosolic ca2+-antagonized mechanism, or caatier (ca2+-antagonized transport into er). significantly, we show that mitochondria supply atp to the er and a serca-dependent ca2+ gra ...201931498082
intravenous delivery of a chemically modified sulfamidase efficiently reduces heparan sulfate storage and brain pathology in mucopolysaccharidosis iiia mice.mucopolysaccharidosis type iiia (mps iiia) is a lysosomal storage disorder (lsd) characterized by severe central nervous system (cns) degeneration. the disease is caused by mutations in the sgsh gene coding for the lysosomal enzyme sulfamidase. sulfamidase deficiency leads to accumulation of heparan sulfate (hs), which triggers aberrant cellular function, inflammation and eventually cell death. there is currently no available treatment against mps iiia. in the present study, a chemically modifie ...201931528541
reprogramming aa catabolism in cho cells with crispr/cas9 genome editing improves cell growth and reduces byproduct secretion.chinese hamster ovary (cho) cells are the preferred host for producing biopharmaceuticals. amino acids are biologically important precursors for cho metabolism; they serve as building blocks for proteogenesis, including synthesis of biomass and recombinant proteins, and are utilized for growth and cellular maintenance. in this work, we studied the physiological impact of disrupting a range of amino acid catabolic pathways in cho cells. we aimed to reduce secretion of growth inhibiting metabolic ...201931526854
collaborative study for the calibration of the replacement international standard for pertussis toxin for use in histamine sensitisation and cho cell clustering assays.pertussis toxin (pt) in its detoxified form is one of the major protective antigens in vaccines against bordetella pertussis (whooping cough). reference preparations of native pt are required for the quality control of pertussis vaccines. stocks of the first who international standard (is) for pt (jnih-5) were low and a replacement was required. one candidate material was donated by a vaccine manufacturer to nibsc. it was formulated, lyophilised into sealed glass ampoules and coded 15/126. an in ...201931526657
gpr40 full agonism exerts feeding suppression and weight loss through afferent vagal nerve.gpr40/ffar1 is a gq protein-coupled receptor expressed in pancreatic β cells and enteroendocrine cells, and mediates insulin and incretin secretion to regulate feeding behavior. several gpr40 full agonists have been reported to reduce food intake in rodents by regulating gut hormone secretion in addition to their potent glucose-lowering effects; however, detailed mechanisms of feeding suppression are still unknown. in the present study, we characterized t-3601386, a novel compound with potent fu ...201931525244
integrated clarification and purification of monoclonal antibodies by membrane based separation of aqueous two-phase systems.therapeutic monoclonal antibodies (mab) are used for the treatment of numerous serious diseases, which have led to an increasing demand over the last decades. increased cell density and mab titer of the cultivation broth lead to great challenges for the subsequent clarification and capture operations in the downstream process. as an alternative approach to the conventional downstream process, a selective mab extraction via an aqueous two-phase system (atps) directly from the cultivation broth of ...201931544846
evaluating the impact of suramin additive on cho cells producing fc-fusion protein.to examine the effects of suramin in cho cell cultures in terms of the cell culture performance and quality of the fc-fusion protein.201931541331
endoglin protein interactome profiling identifies trim21 and galectin-3 as new binding partners.endoglin is a 180-kda glycoprotein receptor primarily expressed by the vascular endothelium and involved in cardiovascular disease and cancer. heterozygous mutations in the endoglin gene (eng) cause hereditary hemorrhagic telangiectasia type 1, a vascular disease that presents with nasal and gastrointestinal bleeding, skin and mucosa telangiectases, and arteriovenous malformations in internal organs. a circulating form of endoglin (alias soluble endoglin, seng), proteolytically released from the ...201931540324
a study on enhanced o-glycosylation strategy for improved production of recombinant human chorionic gonadotropin in chinese hamster ovary cells.human chorionic gonadotropin (hcg) is a glycoprotein hormone that exists as a heterodimer comprised of an α subunit and β subunit linked with disulfide bridges. the β subunit contains four o-glycosylation sites. previous studies have found that the translation of mrna to polypeptides of the β subunit was a severely limiting step for the expression of recombinant hcg protein in chinese hamster ovary (cho) cells. the effects of o-glycosylation on recombinant hcg protein expression were assessed by ...201931604106
model-driven engineering of n-linked glycosylation in chinese hamster ovary cells.chinese hamster ovary (cho) cells are used for industrial production of protein-based therapeutics (i.e., "biologics"). here we describe a method for combining systems-level kinetic models with a synthetic biology platform for multigene overexpression to rationally perturb n-linked glycosylation. specifically, we sought to increase galactose incorporation on a secreted immunoglobulin g (igg) protein. we rationally design, build, and test a total of 23 transgenic cell pools that express single or ...201931596566
efficacy of lenvervimab, a recombinant human immunoglobulin, in treatment of chronic hepatitis b virus infection.the mechanism of action of hepatitis b immunoglobulin (hbig) for chronic hepatitis b (chb) treatment is not fully understood. a clinical trial in japan suggested that hbig therapy might benefit patients with chb.1 lenvervimab, a recombinant monoclonal hbig developed by gc pharma (yongin, south korea), has been screened from an anti-hb-enriched phage-display library cloned from hepatitis b vaccine-boosted human blood cells and was produced in chinese hamster ovary cells.2-4.201931589980
crystal structure of the fab region of a neutralizing antibody against granulocyte-macrophage colony-stimulating factor.an increased level of granulocyte-macrophage colony-stimulating factor has a potential role in the development of autoimmune diseases, and the neutralization of its activity by monoclonal antibodies is a promising therapy for some diseases. here, the crystal structure of the fab region of ev1007, a fully human antibody expressed in chinese hamster ovary cells that was developed from human peripheral blood mononuclear cells, is described. the structure closely resembles that of mb007, which is th ...201931584011
epitope mapping of pmab-225 an anti-alpaca podoplanin monoclonal antibody using flow cytometry.podoplanin (pdpn) is a mucin-type membrane glycoprotein, and possesses three platelet aggregation-stimulating (plag) domains: plag1, plag2, and plag3 at the n-terminus of pdpn, and one or two plag-like domains (plds) in the middle of pdpn. pdpn is expressed on normal tissues, such as podocytes of the kidney and type i alveolar cells of the lung, and is also overexpressed in numerous malignant cancers. previously, we reported a novel anti-alpaca podoplanin (apdpn) monoclonal antibody (mab), pmab- ...201931613697
structure-effect relationships of novel semi-synthetic cannabinoid derivatives.background: as a library of cannabinoid (cb) derivatives with (-)-trans-cannabidiol (cbd) or (-)-trans-cannabidivarin (cbdv) scaffold, we synthesized nine novel cannabinoids: 2-hydroxyethyl cannabidiolate (2-hec), 2-hydroxypentyl cannabidiolate (2-hpc), 2,3-dihydroxypropyl cannabidiolate (gcbd), cyclohexyl cannabidiolate (chc), n-hexyl-cannabidiolate (hc), 2-(methylsulfonamido)ethyl cannabidiolate (nmsc), 2-hydroxyethyl cannabidivarinolate (2-hecbdv), cyclohexyl cannabidivarinolate (chcbdv), and ...201931824305
dual role of cofilin in app trafficking and amyloid-β clearance.the accumulation of amyloid-β (aβ) plays a pivotal early event in the pathogenesis of alzheimer's disease (ad). in the brain, neurons produce aβ by the proteolytic processing of amyloid precursor protein (app) through the endocytic pathway, whereas microglia mediate aβ clearance also via endocytic mechanisms. previous studies have shown the critical importance of cofilin, a filamentous actin-severing protein, in actin dynamics and pathogen-triggered endocytic processes. moreover, the binding of ...201931646885
epitope analysis of an antihorse podoplanin monoclonal antibody pmab-219.podoplanin (pdpn), which is a mucin-type membrane glycoprotein, is expressed on lymphatic endothelial cells and epithelial cells of many organs. pdpn is also overexpressed in several malignant cancers, and its expression is associated with cancer progression and poor prognosis. human pdpn possesses three platelet aggregation-stimulating (plag) domains and the plag-like domain (pld), which binds to c-type lectin-like receptor-2 (clec-2). previously, we reported a novel antihorse pdpn (horpdpn) mo ...201931638470
determination of the pathological features of npc1 variants in a cellular complementation test.niemann-pick type c (np-c) is a rare disorder of lipid metabolism caused by mutations within the npc1 and npc2 genes. np-c is a neurovisceral disease leading to a heterogeneous, multisystemic spectrum of symptoms in those affected. until now, there is no investigative tool to demonstrate the significance of single variants within the npc genes. hence, the aim of the study was to establish a test that allows for an objective assessment of the pathological potential of npc1 gene variants. chinese ...201931635081
radioprotective effect of hydroxyl radical scavengers on prokaryotic and eukaryotic cells under various gamma irradiation conditions.the influence of various hydroxyl radical scavengers such as methanol, ethanol and dimethyl sulfoxide on radiation sensitivity of prokaryotic cells (bacteria escherichia coli) and eukaryotic cells (yeast saccharomyces cerevisiae and v79 cells-chinese hamster pulmonary fibroblasts) irradiated by 60co gamma radiation was investigated. the dependence of radiation sensitivity on dose rate in range from 1.8 to 100 gy h-1 was evaluated. survival of cells irradiated by increasing dose rates was followe ...201931812995
development of rolled scaffold for high-density adherent cell culture.bioreactors for large-scale culture of mammalian cells are playing vital roles in biotechnology and bioengineering. various bioreactors have been developed, but their capacity and efficiency are often limited by insufficient mass transfer rate and high shear stress. a rolled scaffold (rs) is a fully defined scaffold for high-density adherent culture of mammalian cells. the rs is a polymer film with spacers, that is rolled into a cylinder with a pre-determined gap between each turn. cells are cul ...201931813056
tak-925, an orexin 2 receptor-selective agonist, shows robust wake-promoting effects in mice.orexin-producing neurons in the lateral hypothalamus are a critical regulator of sleep/wake states, and their loss is associated with narcolepsy type 1 (nt1). orexin peptides act on two g protein-coupled receptors: orexin 1 receptor (ox1r) and orexin 2 receptor (ox2r). ox2r knockout (ko) mice, but not ox1r ko mice, showed clear narcolepsy-like phenotypes, including fragmented sleep-wake cycles. moreover, ox2r-selective antagonists have been shown to induce sleepiness in mice, and activation of o ...201931654653
application of a genome-scale model in tandem with enzyme assays for identification of metabolic signatures of high and low cho cell producers.biopharmaceutical industrial processes are based on high yielding stable recombinant chinese hamster ovary (cho) cells that express monoclonal antibodies. however, the process and feeding regimes need to be adapted for each new cell line, as they all have a slightly different metabolism and product performance. a main limitation for accelerating process development is that the metabolic pathways underlying this physiological variability are not yet fully understood. this study describes the evol ...201931720213
computer-aided strategies for determining the amino acid composition of medium for chinese hamster ovary cell-based biomanufacturing platforms.chinese hamster ovary (cho) cells are used for the production of the majority of biopharmaceutical drugs, and thus have remained the standard industry host for the past three decades. the amino acid composition of the medium plays a key role in commercial scale biologics manufacturing, as amino acids constitute the building blocks of both endogenous and heterologous proteins, are involved in metabolic and non-metabolic pathways, and can act as main sources of nitrogen and carbon under certain co ...201931684012
complexes formed with integrin-α5 and kcnb1 potassium channel wild type or epilepsy-susceptibility variants modulate cellular plasticity via ras and akt signaling.voltage-gated potassium (k+) channel subfamily b member 1 (kcnb1, kv2.1) and integrin-α5 form macromolecular complexes-named integrin-α5-kcnb1 complexes (ikcs)-in the human brain, but their function was poorly understood. here we report that membrane depolarization triggered ikc intracellular signals mediated by small gtpases of the ras subfamily and protein kinase b (akt) to advance the development of filopodia and lamellipodia in chinese hamster ovary cells, stimulate their motility, and enhan ...201931682765
indomethacin enhances type 1 cannabinoid receptor signaling.in addition to its known actions as a non-selective cyclooxygenase (cox) 1 and 2 inhibitor, we hypothesized that indomethacin can act as an allosteric modulator of the type 1 cannabinoid receptor (cb1r) because of its shared structural features with the known allosteric modulators of cb1r. indomethacin enhanced the binding of [3h]cp55940 to hcb1r and enhanced aea-dependent [35s]gtpγs binding to hcb1r in chinese hamster ovary (cho) cell membranes. indomethacin (1 μm) also enhanced cp55940-depende ...201931680861
identification and profiling of micrornas expressed in oral buccal mucosa squamous cell carcinoma of chinese hamster.micrornas are known to play essential role in the gene expression regulation in cancer. in our research, next-generation sequencing technology was applied to explore the abnormal mirna expression of oral squamous cell carcinoma (oscc) in chinese hamster. a total of 3 novel mirnas (novel-117, novel-118, and novel-135) and 11 known mirnas (crg-mir-130b-3p, crg-mir-142-5p, crg-mir-21-3p, crg-mir-21-5p, crg-mir-542-3p, crg-mir-486-3p, crg-mir-499-5p, crg-mir-504, crg-mir-34c-5p, crg-mir-34b-5p and c ...201931666604
an arginase-based system for selection of transfected cho cells without the use of toxic chemicals.polyamines have essential roles in cell proliferation, dna replication, transcription, and translation processes, with intracellular depletion of putrescine, spermidine, and spermine resulting in cellular growth arrest and eventual death. serum-free media for cho-k1 cells require putrescine supplementation, because these cells lack the first enzyme of the polyamine production pathway, arginase. on the basis of this phenotype, we developed an arginase-based selection system. we transfected cho-k1 ...201931666335
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