PMID(sorted descending)
comparative ecotoxicity of potential biofuels to water flea (daphnia magna), zebrafish (danio rerio) and chinese hamster (cricetulus griseus) v79 cells.the ecotoxicity of two biofuel candidates (1‑octanol and 2‑butanone) was investigated by an integrative test strategy using three bioassays: the acute immobilisation test with water flea (d. magna), the fish embryo acute toxicity test with zebrafish (danio rerio) and the in vitro micronucleus assay with chinese hamster (cricetulus griseus) v79 cells. the median effective concentration (ec50) values were 14.9±0.66mgl-1for 1‑octanol, and 2152.1±44.6mgl-1for 2‑butanone in the d. magna test. both 1‑ ...201829524897
evaluating the interactions between red stingray (dasyatis akajei) melanocortin receptors and elephant shark (callorhinchus milii) mrap1 and mrap2 following stimulation with either stingray acth(1-24) or stingray des-acetyl-αmsh: a pharmacological study in chinese hamster ovary cells.previous studies on bony vertebrate mc2r orthologs (i.e., ray finned fishes, amphibians, reptiles, birds, and mammals) have shown that these mc2r orthologs have an obligatory requirement for interaction with bony vertebrate mrap1 orthologs to a) allow for the trafficking of the mc2r ortholog to the plasma membrane; and b) to allow activation by acth, but not by any msh-sized ligand. in addition, previous studies have found that co-expression of teleost and mammalian mc4r orthologs with correspon ...201829524525
glyco-engineered long acting fgf21 variant with optimal pharmaceutical and pharmacokinetic properties to enable weekly to twice monthly subcutaneous dosing.pharmacological administration of fgf21 analogues has shown robust body weight reduction and lipid profile improvement in both dysmetabolic animal models and metabolic disease patients. here we report the design, optimization, and characterization of a long acting glyco-variant of fgf21. using a combination of n-glycan engineering for enhanced protease resistance and improved solubility, fc fusion for further half-life extension, and a single point mutation for improving manufacturability in chi ...201829523796
protein a affinity chromatography of chinese hamster ovary (cho) cell culture broths containing biopharmaceutical monoclonal antibody (mab): experiments and mechanistic transport, binding and equilibrium modeling.protein a-based affinity chromatography is a highly-efficient separation method to capture, purify and isolate biosimilar monoclonal antibodies (mab) - an important medical product of biopharmaceutical industrial manufacturing. it is considered the most expensive step in purification downstream operations; therefore, its performance optimization offers a great cost saving in the overall production expenditure. the biochemical mixture-separating specific interaction experiments with chinese hamst ...201829522957
glyco-mapper: a chinese hamster ovary (cho) genome-specific glycosylation prediction tool.glyco-mapper is a novel systems biology product quality prediction tool created using a new framework termed: discretized reaction network modeling using fuzzy parameters (dream-zyp). within glyco-mapper, users fix the nutrient feed composition and the glycosylation reaction fluxes to fit the model glycoform to the reference experimental glycoform, enabling cell-line specific glycoform predictions as a result of cell engineering strategies. glyco-mapper accurately predicts glycoforms associated ...201829522825
a comparative study of using free radical generators in the testing of chosen oxidative stress parameters in the different types of cells.the aim of this study was to assess whether there are differences between the results of determining oxidative stress markers obtained from different origin cell lines after exposure to chemicals generating free radicals. the studies considered two markers of oxidative stress: the level of thiobarbituric acid reactive substances (tbars) and superoxide dismutase activity. the evaluation was performed in five cell lines: chinese hamster ovary (cho-9) cells, lung adenocarcinoma a549, macrophages ra ...201829519201
antibacterial effect of copaifera duckei dwyer oleoresin and its main diterpenes against oral pathogens and their cytotoxic effect.this study evaluates the antibacterial activity of the copaifera duckei dwyer oleoresin and two isolated compounds [eperu-8(20)-15,18-dioic acid and polyalthic acid] against bacteria involved in primary endodontic infections and dental caries and assesses the cytotoxic effect of these substances against a normal cell line. mic and mbc assays pointed out the most promising metabolites for further studies on bactericidal kinetics, antibiofilm activity, and synergistic antibacterial action. the ole ...201829515530
role of microvesicles in the spread of herpes simplex virus type 1 in oligodendrocytic cells.herpes simplex virus type 1 (hsv-1) is a neurotropic pathogen that can infect many types of cells and establishes latent infections in neurons of sensory ganglia. in some cases, the virus spreads into the cns causing encephalitis or meningitis. cells infected with several different types of viruses may secrete microvesicles containing viral proteins and rnas. in some instances, extracellular microvesicles harboring infectious virus have been found. here we describe the features of shedding micro ...201829514899
biogenesis of silver nanoparticles using leaf extract of indigofera hirsuta l. and their potential biomedical applications (3-in-1 system).the present study reports the biosynthesis of silver nanoparticles (ih-agnps) using aqueous leaf extract of indigofera hisruta l. the biosynthesized ih-agnps were found to be fcc crystals, 5-10 nm in size, spherical in shape and stable. the biosynthesized ih-agnps showed dose-dependant cytotoxicity against prostate cancer (pc3) (ic50 = 68.5 μg/ml), colon cancer (colo205) (ic50 = 85.2 μg/ml), and mouse melanoma (b16f10) (ic50 = 80.9 μg/ml). ih-agnps were found to be nontoxic towards normal cho (c ...201829513113
the combined effect of pdx1 overexpression and shh manipulation on the function of insulin-producing cells derived from adipose-tissue stem cells.pancreatic and duodenal homeobox 1 (pdx1) and sonic hedgehog (shh) are the key regulators of beta-cell function. in vitro experiments have shown that there is significant cooperation between pdx1 and shh with regard to the production and maintenance of insulin-producing cells (ipcs). in this study, the combined effect of pdx1 overexpression and shh manipulation on the function of adipose tissue-derived ipcs was determined. a eukaryotic expression vector (pdx1- pcdna3.1(+)) was constructed and tr ...201829511614
antioxidant activity of ge-132, a synthetic organic germanium, on cultured mammalian is a synthetic organic germanium that is used as a dietary supplement. the antioxidant activity of ge-132 on cultured mammalian cells was investigated in this study. first, ge-132 cytotoxicity on mammalian cultured cells was determined by measuring lactate dehydrogenase (ldh) levels. ge-132 had no cytotoxic effect on three different cell lines. second, the cell proliferative effect of ge-132 was determined by measuring atp content of whole cells and counting them. ge-132 treatment of chin ...201829503400
assessment of the predictive capacity of the optimized in vitro comet assay using hepg2 cells.evaluation of dna damage is critical during the development of new drugs because it is closely associated with genotoxicity and carcinogenicity. the in vivo comet assay to assess dna damage is globally harmonized as oecd tg 489. however, a comet test guideline that evaluates dna damage without sacrificing animals does not yet exist. the goal of this study was to select an appropriate cell line for optimization of the in vitro comet assay to assess dna damage. we then evaluated the predictivity o ...201829502738
pm2.5 obtained from urban areas in beijing induces apoptosis by activating nuclear factor-kappa b.particulate matter (pm), which has adverse effects on citizen health, is a major air pollutant in beijing city. pm2.5 is an indicator of pm in urban areas and can cause serious damage to human health. many epidemiological studies have shown that nuclear factor-kappa b (nf-κb) is involved in pm2.5-induced cell injury, but the exact mechanisms are not well understood.201729502513
engineering a stable cho cell line for the expression of a mers-coronavirus vaccine antigen.middle east respiratory syndrome coronavirus (mers-cov) has infected at least 2040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. to address this need, we are developing a subunit recombinant protein vaccine comprising residues 377-588 of the mers-cov spike protein receptor-binding domain (rbd), which, when formulated with the addavax adjuvant, it induces a significant neutralizing antibody respon ...201829496347
cell-based glycan arrays for probing glycan-glycan binding protein interactions.glycan microarrays provide a high-throughput means of profiling the interactions of glycan-binding proteins with their ligands. however, the construction of current glycan microarray platforms is time consuming and expensive. here, we report a fast and cost-effective method for the assembly of cell-based glycan arrays to probe glycan-glycan-binding protein interactions directly on the cell surface. chinese hamster ovary cell mutants with a narrow and relatively homogeneous repertoire of glycofor ...201829491407
functional characterization of recombinant snake venom rhodocytin: rhodocytin mutant blocks clec-2/podoplanin-dependent platelet aggregation and lung metastasis.essentials we generated recombinant rhodocytin that could aggregate platelets via clec-2. recombinant wild-type rhodocytin formed heterooctamer with four α- and β-subunits. asp 4 in α-subunit of rhodocytin was required for binding to clec-2. inhibitory mutant of rhodocytin blocked podoplanin-dependent hematogenous metastasis.201829488681
visualisation of intracellular production bottlenecks in suspension-adapted cho cells producing complex biopharmaceuticals using fluorescence microscopy.with the advance of complex biological formats such as bispecific antibodies or fusion proteins, mammalian expression systems often show low performance. described determining factors may be accumulation or haltering of heterologous proteins within the different cellular compartments disturbing transport or secretion. in case of the investigated bispecific antibody (bsab)-producing chinese hamster ovary (cho) cell line neither impaired transcription nor decreased translation processes were ident ...201829477386
an rna-seq based transcriptomic investigation into the productivity and growth variants with chinese hamster ovary cells.chinese hamster ovary (cho) cells are widely used in producing monoclonal antibodies (mabs), however, these cell lines can show variants associated with productivity and growth. fundamental understanding of cellular mechanisms can benefit high mabs production while maintaining robust cell growth. in this study, rna sequencing (rna-seq) based approach was used to study the transcriptomic space among three mab-producing cho cell lines. a phenotypic contrast of higher productivity but lower growth ...201829476805
function of the natalisin receptor in mating of the oriental fruit fly, bactrocera dorsalis (hendel) and testing of peptidomimetics.natalisins (ntls) are conservative neuropeptides, which are only found in arthropods and are documented to regulate reproductive behaviors in insects. in our previous study, we have confirmed that ntls regulate the reproductive process in an important agricultural pest, bactrocera dorsalis (hendel). hence, in this study, to further confirm the in vivo function of ntl receptor (ntlr) and assess the potential of ntlr as an insecticide target, rna interference targeting ntlr mrna was performed. we ...201829474388
genetic engineering of host organisms for pharmaceutical synthesis.pharmaceutical production hosts may be derived from almost any organism, from chinese hamster ovary (cho) cell lines to isolated actinomycetes. each host can be improved, historically only through adaptive evolution. recently, the maturation of organism engineering has expanded the available models, methods, and tools for altering host phenotypes. new tools like crispr-associated endonucleases promise to enable precise cellular reprogramming and to access previously intractable hosts. in this re ...201829471209
understanding biopharmaceutical production at single nucleotide resolution using ribosome footprint profiling.biopharmaceuticals such as monoclonal antibodies have revolutionised the treatment of a variety of diseases. the production of recombinant therapeutic proteins, however, remains expensive due to the manufacturing complexity of mammalian expression systems and the regulatory burden associated with administrating these medicines to patients in a safe and efficacious manner. in recent years, academic and industrial groups have begun to develop a greater understanding of the biology of host cell lin ...201829471208
smad4-independent activation of tgf-β signaling by muc1 in a human pancreatic cancer cell line.pancreatic ductal adenocarcinoma (pda) has a mortality rate that nearly matches its incidence rate. transforming growth factor beta (tgf-β) is a cytokine with a dual role in tumor development switching from a tumor suppressor to a tumor promoter. there is limited knowledge of how tgf-β function switches during tumorigenesis. mucin 1 (muc1) is an aberrantly glycosylated, membrane-bound, glycoprotein that is overexpressed in >80% of pda cases and is associated with poor prognosis. in pda, muc1 pro ...201829467938
probing lactate metabolism variations in large-scale bioreactors.lactate metabolism variations are frequently encountered in mammalian cell culture processes, especially during process scale-up. in this study, we took a multipronged approach to investigate the impact of ph, pco2 , osmolality, base addition, and mixing conditions on the observed lactate variations in a chinese hamster ovary (cho) fed-batch process at 2,000 l scale. two cultivating methods, co2 -controlled and ph-controlled, were used to decouple the individual and synergistic effects from thos ...201829464875
antibody glycoengineering strategies in mammalian a key parameter impacting functional and structural heterogeneity, protein glycosylation is a critical quality attribute for antibody biotherapeutic manufacturing. the glycan patterns on recombinant antibodies, particularly on the conserved fragment crystallizable (fc) region, can have significant effects on an antibody's functional activities including clearance rate, antibody-dependent cellular cytotoxicity (adcc), complement-dependent cytotoxicity (cdc), and anti-inflammatory activity. in ...201829457629
hyaluronate coating enhances the delivery and biocompatibility of gold nanoparticles.for targeted delivery with nanoparticles (nps) as drug carriers, it is imperative that the nps are internalized into the targeted cell. surface properties of nps influence their interactions with cells. we examined the responses of retinal pigment epithelial cells, nih 3t3 fibroblast cells, and chinese hamster ovary cells to gold nanoparticles (au nps) in their nascent form as well as coated with end-thiolated hyaluronate (hs-ha). the grafting density of hs-ha on au nps was calculated based on t ...201829455984
in vitro antileishmanial and cytotoxicity activities of essential oils from haplophyllum tuberculatum a. juss leaves, stems and aerial parts.plants used for traditional medicine produce diverse and complex secondary metabolites exhibiting various medicinal properties. the medicinal plant haplophyllum tuberculatum is used by native people against malaria and parasitic infections.201829444667
l-cysteine capped cdse quantum dots synthesized by photochemical route.l-cysteine capped cdse quantum dots were synthesized via photochemical route in aqueous solution under uv photo-irradiation. the as grown cdse quantum dots exhibit broad fluorescence at room temperature. the cdse quantum dots were found to be formed only through the reactions of the precursors, i.e., cd(nh3)2+4 and seso2-3 with the photochemically generated 1-hydroxy-2-propyl radicals, (ch3)2coh radicals, which are formed through the process of h atom abstraction by the photoexcited acetone from ...201829442847
sv40 intron, a potent strong intron element that effectively increases transgene expression in transfected chinese hamster ovary cells.chinese hamster ovary (cho) cells have become the most widely utilized mammalian cell line for the production of recombinant proteins. however, the product yield and transgene instability need to be further increased and solved. in this study, we investigated the effect of five different introns on transgene expression in cho cells. hcmv intron a, adenovirus tripartite leader sequence intron, sv40 intron, chinese hamster ef-1alpha gene intron 1 and intervening sequence intron were cloned downstr ...201829441681
enhancement of glycosylation by stable co-expression of two sialylation-related enzymes on chinese hamster ovary cells.sialic acid plays important roles in stabilization and modulation of the interaction of molecules and membranes in organisms. due to its high electronegativity, sialic acid can promote binding effects of molecules and support the transportation of drugs and ions in cells. this also strengthens cells against degradation from glycosidases and proteases. hence sialic acid helps glycoproteins extend their half-lives and bioactivity. on the other hand, chinese hamster ovary (cho) cells have been wide ...201829439861
analysis of peptide ligand specificity of different insect adipokinetic hormone receptors.adipokinetic hormone (akh) is a highly researched insect neuropeptide that induces the mobilization of carbohydrates and lipids from the fat body at times of high physical activity, such as flight and locomotion. as a naturally occurring ligand, akh has undergone quite a number of amino acid changes throughout evolution, and in some insect species multiple akhs are present. akh acts by binding to a rhodopsin-like g protein-coupled receptor, which is related to the vertebrate gonadotropin-releasi ...201829439466
using a dihydrofolate reductase-based strategy for producing the biosimilar version of pertuzumab in cho-s cells.targeted therapy using monoclonal antibodies (mabs) against epidermal growth factor receptor-2 (erbb2) has been utilized for the treatment of breast cancer, recently. pertuzumab, one of the anti-erbb2 mabs, was approved by fda in 2012 for the treatment of metastatic breast cancer. the aim of this study was to produce biosimilar version of pertuzumab in chinese hamster ovary (cho)-s cell line, and compare its erbb2-binding and biological activities, with commercial drug, perjeta. to this end, a d ...201829437532
strategy for generating sequence-defined aptamer reagent sets for detecting protein contaminants in biotherapeutics.biologic drugs are typically manufactured in mammalian host cells, and it is critical from a drug safety and efficacy perspective to detect and remove host cell proteins (hcps) during production. this is currently achieved with sets of polyclonal antibodies (pabs), but these suffer from critical shortcomings because their composition is inherently undefined, and they cannot detect nonimmunogenic hcps. in this work, we report a high-throughput screening and array-based binding characterization st ...201829436820
butyrated mannac analog improves protein expression in chinese hamster ovary cells.the chemical additive sodium butyrate (nabu) has been applied in cell culture media as a direct and convenient method to increase the protein expression in chinese hamster ovary (cho) and other mammalian cells. in this study, we examined an alternative chemical additive, 1,3,4-o-bu3 mannac, for its effect on recombinant protein production in cho. supplementation with 1,3,4-o-bu3 mannac for two stable cho cell lines, expressing human erythropoietin or igg, enhanced protein expression for both pro ...201829427449
tumor targeting with novel pyridyl 6-substituted pyrrolo[2,3- d]pyrimidine antifolates via cellular uptake by folate receptor α and the proton-coupled folate transporter and inhibition of de novo purine nucleotide biosynthesis.tumor-targeted specificities of 6-substituted pyrrolo[2,3- d]pyrimidine analogues of 1, where the phenyl side-chain is replaced by 3',6' (5, 8), 2',5' (6, 9), and 2',6' (7, 10) pyridyls, were analyzed. proliferation inhibition of isogenic chinese hamster ovary (cho) cells expressing folate receptors (frs) α and β were in rank order, 6 > 9 > 5 > 7 > 8, with 10 showing no activity, and 6 > 9 > 5 > 8, with 10 and 7 being inactive, respectively. antiproliferative effects toward frα- and frβ-expressi ...201829425443
inhibitory effect of bofutsushosan (fang feng tong sheng san) on glucose transporter 5 function in vitro.bofutsushosan (bts; fang feng tong sheng san in chinese) is a formula in traditional japanese kampo medicine and chinese medicine comprising eighteen crude drugs, and is used to treat obesity and metabolic syndrome. fructose is contained in refreshing beverages as high-fructose corn syrup, and is associated with obesity. fructose is absorbed via glucose transporter 5 (glut5) in the intestine. therefore, the inhibition of glut5 is considered to be a target of obesity drugs. we evaluated the inhib ...201829423591
"antimicrobial and antiproliferative activity of essential oil, aqueous and ethanolic extracts of ocimum micranthum willd leaves".ocimum micranthum willd is a plant used in traditional medicine practiced in the region of the yucatan peninsula. in particular, it is used for the treatment of cutaneous infections and wound healing, however there are currently no existing scientific studies that support these applications. the aim of the present study was to evaluate the antimicrobial and the in vitro proliferative activity (on healthy mammalian cell lines) of the essential oil and extracts (aqueous and ethanolic) of this plan ...201829422064
comparison of the in vitro toxicological activity of various particulate matter.ultrafine particles (ufps, < 2.5 µm) in air pollutants have been identified as a major cause of respiratory diseases, since they can affect the lung alveoli through the bronchus. in particular, if toxicants such as heavy metals and polycyclic aromatic hydrocarbons (pahs) are present in ufps, they can cause diseases such as asthma, chronic obstructive pulmonary disease, and lung cancer. this study compared in vitro toxicity of various particulate matter including ufps from combustion particles of ...201829415641
characterization of glycoengineered anti-her2 monoclonal antibodies produced by using a silkworm-baculovirus expression system.silkworm-baculovirus expression systems are efficient means for the production of recombinant proteins that provide high expression levels and post-translational modifications. here, we characterized the stability, glycosylation pattern and antibody-dependent cell-mediated cytotoxicity activity of anti-her2 monoclonal antibodies containing native or glycoengineered mammalian-like n-glycans that were produced by using a silkworm-baculovirus expression system. compared with a monoclonal antibody p ...201829415204
debottlenecking protein secretion and reducing protein aggregation in the cellular host.chinese hamster ovary (cho) cells have been extensively used for industrial production of biotherapeutics. with advances in cell line development and process optimization, production levels of therapeutic proteins using the cho expression system have increased to beyond 10g per liter scale. these high-titer processes could challenge the secretory capacity of cho cells, which can result in degradation and aggregation of the protein of interest. this review discusses bottlenecks in the secretory p ...201829414073
applications of proteomic methods for cho host cell protein characterization in biopharmaceutical manufacturing.chinese hamster ovary (cho) cells are the most prevalent host organism for production of recombinant therapeutic proteins, including monoclonal antibodies (mabs). regulatory guidance mandates control of the host cell protein (hcp) concentration in the production process, which remains a primary challenge. although hcp concentrations are typically measured by elisa, orthogonal proteomic methods are gaining popularity for identification and quantitation of individual hcp species. recent applicatio ...201829414072
a quantitative pcr-based assay reveals that nucleotide excision repair plays a predominant role in the removal of dna-protein crosslinks from plasmids transfected into mammalian cells.dna-protein crosslinks (dpcs) are complex dna lesions that induce mutagenesis and cell death. dpcs are created by common antitumor drugs, reactive oxygen species, and endogenous aldehydes. since these agents create other types of dna damage in addition to dpcs, identification of the mechanisms of dpc repair is challenging. in this study, we created plasmid substrates containing site-specific dpc lesions, as well as plasmids harboring lesions that are selectively repaired by the base excision or ...201829413806
grp78 protects cho cells from ribosylation.d-ribose (rib), a reactive glycation compound that exists in organisms, abnormally increases in the urine of diabetic patients and can yield large amounts of advanced glycation end products (ages), leading to cell dysfunction. however, whether cellular proteins are sensitive to this type of glycation is unknown. in this study, we found that cellular ages accumulate in chinese hamster ovary (cho) cells with increased rib concentration and administration time. mass spectrum analysis of isolated ag ...201829410209
both the ph domain and n-terminal region of oxysterol-binding protein related protein 8s are required for localization to pm-er contact sites.oxysterol-binding protein-related proteins are implicated in the sensing and transporting lipids at the membrane contact sites. one of the members of the mammalian orp family, orp8, is thought to transport lipids through directly tethering both er and pm membranes. targeting to pm is thought to be mediated by n-terminal pleckstrin homology domain via binding to phosphoinositides. sequence alignments and nmr structural determination revealed that the ph domain of orp8 is atypical and contains an ...201829409900
rimonabant, a potent cb1 cannabinoid receptor antagonist, is a gαi/o protein inhibitor.rimonabant is a potent and selective cannabinoid cb1 receptor antagonist widely used in animal and clinical studies. besides its antagonistic properties, numerous studies have shown that, at micromolar concentrations rimonabant behaves as an inverse agonist at cb1 receptors. the mechanism underpinning this activity is unclear. here we show that micromolar concentrations of rimonabant inhibited gαi/o-type g proteins, resulting in a receptor-independent block of g protein signaling. accordingly, r ...201829407764
13 c flux analysis reveals that rebalancing medium amino acid composition can reduce ammonia production while preserving central carbon metabolism of cho cell cultures.13 c metabolic flux analysis (mfa) provides a rigorous approach to quantify intracellular metabolism of industrial cell lines. in this study, 13 c mfa was used to characterize the metabolic response of chinese hamster ovary (cho) cells to a novel medium variant designed to reduce ammonia production. ammonia inhibits growth and viability of cho cell cultures, alters glycosylation of recombinant proteins, and enhances product degradation. ammonia production was reduced by manipulating the amino ac ...201829405605
receptor-specific crosstalk between prostanoid e receptor 3 and bombesin receptor subtype 3.bombesin receptor subtype 3 (brs-3) is a gpcr that is expressed in the cns, peripheral tissues, and tumors. our understanding of brs-3's role in physiology and pathophysiology is limited because its natural ligand is unknown. in an attempt to identify this ligand, we screened toad skin ( bufo bufo gargarizans cantor) extracts and identified prostaglandins as putative ligands. in brs-3-transfected human embryonic kidney (hek) cells, we found that prostaglandins, with prostaglandin e2 (pge2) being ...201829401613
a novel bicistronic gene design couples stable cell line selection with a fucose switch in a designer cho host to produce native and afucosylated glycoform antibodies.the conserved glycosylation site asn297 of a monoclonal antibody (mab) can be decorated with a variety of sugars that can alter mab pharmacokinetics and recruitment of effector proteins. antibodies lacking the core fucose at asn297 (afucosylated mabs) show enhanced antibody-dependent cell-mediated cytotoxicity (adcc) and increased efficacy. here, we describe the development of a robust platform for the manufacture of afucosylated therapeutic mabs by engineering a chinese hamster ovary (cho) host ...201829400603
impact of cho metabolism on cell growth and protein production: an overview of toxic and inhibiting metabolites and nutrients.for over three decades, chinese hamster ovary (cho) cells have been the chosen expression platform for the production of therapeutic proteins with complex post-translational modifications. however, the metabolism of these cells is far from perfect and optimized, and requires substantial know how and process optimization and monitoring to perform efficiently. one of the main reasons for this is the production and accumulation of toxic and growth-inhibiting metabolites during culture. lactate and ...201829393587
genotoxicity evaluation of so-ochim-tang-gamibang (socg), a herbal (socg) is a traditional korean medicine frequently used for depression in the clinical field. in this study, we evaluated the potential genotoxicity of socg using three standard batteries of tests as part of a safety evaluation.201829391062
improving titer while maintaining quality of final formulated drug substance via optimization of cho cell culture conditions in low-iron chemically defined media.during biopharmaceutical process development, it is important to improve titer to reduce drug manufacturing costs and to deliver comparable quality attributes of therapeutic proteins, which helps to ensure patient safety and efficacy. we previously reported that relative high-iron concentrations in media increased titer, but caused unacceptable coloration of a fusion protein during early-phase process development. ultimately, the fusion protein with acceptable color was manufactured using low-ir ...201829388872
functional characterization of oligopeptide transporter 1 of dairy is well known that peptides play a vital role in the nutrition and health of dairy cows. bovine oligopeptide transporter 1 (bpept1) is involved in the peptide transport process in the gastrointestinal tracts of dairy cows. however, little information is known in the characteristics of bpept1. therefore, the purpose of this study was to characterize bpept1 functionally using a mammalian cell expression system. the uptake of radiolabeled dipeptide glycyl-sarcosine ([3h]-gly-sar) into the bpept1 ...201829387385
mild hypothermic culture conditions affect residual host cell protein composition post-protein a cell proteins (hcps) are endogenous impurities, and their proteolytic and binding properties can compromise the integrity, and, hence, the stability and efficacy of recombinant therapeutic proteins such as monoclonal antibodies (mabs). nonetheless, purification of mabs currently presents a challenge because they often co-elute with certain hcp species during the capture step of protein a affinity chromatography. a quality-by-design (qbd) strategy to overcome this challenge involves identify ...201829381421
exploring the potential application of short non-coding rna-based genetic circuits in chinese hamster ovary cells.the majority of cell engineering for recombinant protein production to date has relied on traditional genetic engineering strategies, such as gene overexpression and gene knock-outs, to substantially improve the production capabilities of chinese hamster ovary (cho) cells. however, further improvements in cellular productivity or control over product quality is likely to require more sophisticated rational approaches to coordinate and balance cellular pathways. for these strategies to be impleme ...201829377624
preclinical characterization of three transient receptor potential vanilloid receptor 1 antagonists for early use in human intradermal microdose analgesic studies.the transient receptor potential vanilloid receptor 1 (trpv1) is a nonselective cation channel involved in the mediation of peripheral pain to the central nervous system. as such, the trpv1 is an accessible molecular target that lends itself well to the understanding of nociceptive signalling. this study encompasses preclinical investigations of three molecules with the prospect to establish them as suitable analgesic model compounds in human intradermal pain relief studies.201829377430
eel kisspeptins: identification, functional activity, and inhibition on both pituitary lh and gnrh receptor expression.the european eel (anguilla anguilla) presents a blockade of sexual maturation at a prepubertal stage due to a deficient production of gonadotropins. we previously initiated, in the eel, the investigation of the kisspeptin system, one of the major gatekeepers of puberty in mammals, and we predicted the sequence of twokissgenes. in the present study, we cloned and sequencedkiss1andkiss2cdnas from the eel brain. the tissue distributions ofkiss1andkiss2transcripts, as investigated by quantitative re ...201729375473
in vitro genotoxicity assessment of dinitroaniline herbicides pendimethalin and trifluralin.pendimethalin and trifluralin are widely used dinitroaniline herbicides. both compounds can be found as residue levels in agricultural products. this study was conducted in order to provide necessary information for the risk assessment of pendimethalin and trifluralin. in this study, reactive oxygen species (ros) levels were measured to examine the potential of both compounds to induce oxidative damage in chinese hamster lung fibroblast (v79) cells. also, the genotoxic effects of pendimethalin a ...201829374591
ring finger protein 145 (rnf145) is a ubiquitin ligase for sterol-induced degradation of hmg-coa reductase.cholesterol biosynthesis is tightly regulated in the cell. for example, high sterol concentrations can stimulate the degradation of the rate-limiting cholesterol biosynthesis enzyme 3-hydroxy-3-methylglutaryl-coenzyme a reductase (hmg-coa reductase, hmgcr). hmgcr is broken down by endoplasmic reticulum (er) membrane-associated protein complexes consisting of insulin-induced genes (insigs) and the e3 ubiquitin ligase gp78. here, we found that hmgcr degradation is partially blunted in chinese hams ...201829374057
design and evaluation of a novel flavonoid-based radioprotective agent utilizing monoglucosyl this study, three novel flavonoid composite materials, created by combining an aglycone [quercetin (que), hesperetin (hes) or naringenin (nar)] with monoglucosyl rutin (mgr), were designed to test for improved radioprotectivity compared with that provided by administration of mgr alone. aglycone in the mgr-composite state was highly soluble in water, compared with aglycone alone dissolved in dimethyl sulfoxide or distilled water. the antioxidant activity of the three flavonoid composites was ...201829373678
investigation into the mechanism of homo- and heterodimerization of angiotensin-converting enzyme.angiotensin-converting enzyme (ace) plays a central role in the renin-angiotensin system (ras), which is primarily responsible for blood pressure homeostasis. studies have shown that ace inhibitors yield cardiovascular benefits that cannot be entirely attributed to the inhibition of ace catalytic activity. it is possible that these benefits are due to interactions between ace and ras receptors that mediate the protective arm of the ras, such as the angiotensin-ii receptor type 2 (at2r) and the r ...201829371233
development of a novel 99m tc-labelled small molecular antagonist for cxcr4 positive tumor imaging.the chemokine receptor 4 (cxcr4) has been an attractive molecular target for tumor imaging, since it is overexpressed in many tumor types and involved in tumor progression and metastasis. the purpose of this study is to examine the cxcr4 targeting properties of 99m tc-labeled amd3465, a small molecule antagonist of cxcr4. 99m tc-amd3465 was prepared in high yield (>95%) and stable in mice serum at least for 4 h. in vitro cell binding experiments were performed with cho (chinese hamster ovary), m ...201829370457
opp labelling enables total protein synthesis quantification in cho production cell lines at the single-cell level.accurate measurement of global and specific protein synthesis rates becomes increasingly important, especially in the context of biotechnological applications such as process modelling or selection of production cell clones. while quantification of total protein translation across whole cell populations is easily achieved, methods that are capable of tracking population dynamics at the single-cell level are still lacking. to address this need, we applied o-propargyl-puromycin (opp) labelling to ...201829369524
enhanced production of anti-pd1 antibody in cho cells through transient co-transfection with anti-apoptotic genes bcl-x l and mcl-1.apoptosis has a negative impact on the cell survival state during cell cultivation. to optimize mammalian cell culture for production of biopharmaceuticals, one of the important approaches is to extend cell life through over-expression of anti-apoptotic genes. here, we reported a cost-effective process to enhance cell survival and production of an antibody through transient co-transfection with anti-apoptotic genes bcl-x l or mcl-1 in chinese hamster ovary (cho) cells with polyethylenimine (pei) ...201829368032
development of novel oxazolo[5,4-d]pyrimidines as competitive cb2 neutral antagonists based on scaffold hopping.a series of novel oxazolo[5,4-d]pyrimidines was designed via a scaffold hopping strategy and synthesized through a newly developed approach. all these compounds were evaluated for their biological activity toward cb1/cb2 cannabinoid receptors, their metabolic stability in mice liver microsomes and their cytotoxicity against several cell lines. eight compounds have been identified as cb2 ligands with ki values less than 1 μm. it is noteworthy that 2-(2-chlorophenyl)-5-methyl-7-(4-methylpiperazin- ...201829360044
using titer and titer normalized to confluence are complementary strategies for obtaining chinese hamster ovary cell lines with high volumetric productivity of etanercept.the selection of clonally-derived chinese hamster ovary (cho) cell lines with the highest production rate of recombinant glycoproteins remains a big challenge during early stages of cell line development. different strategies using either product titer or product titer normalized to cell number are being used to assess suspension-adapted clones when grown statically in microtiter plates. however, no reported study so far has performed a direct head-to-head comparison of these two early reporters ...201829359860
the genotoxicity of an aqueous extract of gyejibokryeong-hwan.gyejibokryeong-hwan (guizhi fuling wan in china), a mixture of five herbal plants, is a well-known treatment for renal diseases including those associated with climacteric syndrome. however, the genotoxicity of gyejibokryeong-hwan has not yet been well established.201829357857
ampulexins: a new family of peptides in venom of the emerald jewel wasp, ampulex compressa.the parasitoid wasp ampulex compressa injects venom directly into the brain and subesophageal ganglion of the cockroach periplaneta americana, inducing a seven to ten day lethargy termed hypokinesia. hypokinesia presents as a significant reduction in both escape response and spontaneous walking. we examined aminergic and peptidergic components of milked venom with hplc and maldi-tof mass spectrometry. hplc coupled with electrochemical detection confirmed presence of dopamine in milked venom, whi ...201829350905
generation and characterization of siglec-f-specific monoclonal antibodies.siglec-f (sf) is a surface glycoprotein expressed by mouse eosinophils and induces caspase- and mitochondria-dependent apoptosis after engagement with its cognate ligand or specific antibodies. this targeting eosinophils by monoclonal antibodies may help diverse diseases associated with increased frequency of eosinophils including allergy and asthma. in this paper, production of murine and rat monoclonal antibodies (mabs) against siglec-f has been addressed. balb/c mice were immunized with sigle ...201729338152
inhibition of apoptosis using exosomes in chinese hamster ovary cell culture.animal cell culture technology for therapeutic protein production has shown significant improvement over the last few decades. chinese hamster ovary (cho) cells have been widely adapted for the production of biopharmaceutical drugs. in the biopharmaceutical industry, it is crucial to develop cell culture media and culturing conditions to achieve the highest productivity and quality. however, cho cells are significantly affected by apoptosis in the bioreactors, resulting in a substantial decrease ...201829337363
use of the real time xcelligence system for purposes of medical microbiology.roche's xcelligence impedance-measuring instrument is one of a few commercially available systems of such type. according to the best knowledge of authors, instrument was tested so far only for eukaryotic cell research. the aim of this work was to estimate xcelligence suitability for the microbiological tests, including (i) measurement of morphological changes in eukaryotic cells as a result of bacterial toxin activity, (ii) measurement of bacterial biofilm formation and (iii) impact of antisept ...201229334048
changes in chromosome counts and patterns in cho cell lines upon generation of recombinant cell lines and subcloning.chinese hamster ovary cells are the number one production system for therapeutic proteins. a pre-requirement for their use in industrial production of biopharmaceuticals is to be clonal, thus originating from a single cell in order to be phenotypically and genomically identical. in the present study it was evaluated whether standard procedures, such as the generation of a recombinant cell line in combination with selection for a specific and stable phenotype (expression of the recombinant produc ...201829328552
substance p as a putative efferent transmitter mediates gabaergic inhibition in mouse taste buds.capsaicin-mediated modulation on taste nerve responses is thought to be produced indirectly by actions of neuropeptides, e.g., calcitonin gene-related peptide (cgrp) and substance p (sp), onto taste cells implying playing a role in taste sensitivity. during processing gustatory information in taste buds, cgrp shapes peripheral taste signals via serotonergic signaling. the underlying assumption has been that sp exerts its effects on taste transmitter secretion in taste buds of mice.201829328505
the b cell death function of obinutuzumab-hdel produced in plant (nicotiana benthamiana l.) is equivalent to obinutuzumab produced in cho cells.plants have attracted attention as bio-drug production platforms because of their economical and safety benefits. the preliminary efficacy of zmapp, a cocktail of antibodies produced in n. benthamiana (nicotiana benthamiana l.), suggested plants may serve as a platform for antibody production. however, because the amino acid sequences of the fab fragment are diverse and differences in post-transcriptional processes between animals and plants remain to be elucidated, it is necessary to confirm fu ...201829324849
sirt3 activator honokiol attenuates β-amyloid by modulating amyloidogenic pathway.honokiol (poly-phenolic lignan from magnolia grandiflora) is a sirtuin-3 (sirt3) activator which exhibit antioxidant activity and augment mitochondrial functions in several experimental models. modern evidence suggests the critical role of sirt3 in the progression of several metabolic and neurodegenerative diseases. amyloid beta (aβ), the precursor to extracellular senile plaques, accumulates in the brains of patients with alzheimer's disease (ad) and is related to the development of cognitive i ...201829324783
multiplexed digital mrna expression analysis profiles system-wide changes in mrna abundance and responsiveness of upr-specific gene expression changes during batch culture of recombinant chinese hamster ovary cells.the unfolded protein response (upr) signalling pathway is viewed as critical for setting the effectiveness of recombinant protein expression in cho cells. in this study, we used nanostring ncounter technology to study expression of a group of genes associated with cellular processes linked to upr activation under er stress and the changing environment of a batch culture. time course induction of er stress, using tunicamycin (tm), showed a group of genes such as chop, trb3, sqstm1, grp78 and herp ...201829323465
development of a chemically defined platform fed-batch culture media for monoclonal antibody-producing cho cell lines with optimized choline content.a chemically defined platform basal medium and feed media were developed using a single chinese hamster ovary (cho) cell line that produces a monoclonal antibody (mab). cell line a, which showed a peak viable cell density of 5.9 × 106 cells/ml and a final mab titer of 0.5 g/l in batch culture, was selected for the platform media development. stoichiometrically balanced feed media were developed using glucose as an indicator of cell metabolism to determine the feed rates of all other nutrients. a ...201829322349
effectiveness of aqueous and hydroalcoholic extracts of acanthospermum australe (loefl.) kuntze against diarrhea-inducing bacteria.leaves and roots of acanthospermum australe (asteraceae) have been used in brazilian folk medicine for the treatment of various ailments including diarrhea, skin diseases, blennorrhagia, dyspepsia, parasitic worms and malaria. the aim of study was to characterize the chemical profiles of the aqueous and hydroalcoholic extracts of leaves and roots of a. australe, and to evaluate their antimicrobial activities against diarrhea-inducing bacteria (enterococcus faecalis, shigella dysenteriae and yers ...201829319752
rna-seq highlights high clonal variation in monoclonal antibody producing cho cells.the development of next-generation sequencing technologies has opened new opportunities to better characterize complex eukaryotic cells. chinese hamster ovary (cho) cells play a primary role in therapeutic protein production, with currently five of the top ten blockbuster drugs produced in cho. however, engineering superior cho cells with improved production features has had limited success to date and cell lines are still developed through the generation and screening of large strain pools. her ...201829316330
glycoengineering in cho cells: advances in systems biology.for several decades, glycoprotein biologics have been successfully produced from chinese hamster ovary (cho) cells. the therapeutic efficacy and potency of glycoprotein biologics are often dictated by their post translational modifications, particularly glycosylation, which unlike protein synthesis, is a non-templated process. consequently, both native and recombinant glycoprotein production generate heterogeneous mixtures containing variable amounts of different glycoforms. stability, potency, ...201829316325
methods for using small non-coding rnas to improve recombinant protein expression in mammalian cells.the ability to produce recombinant proteins by utilizing different "cell factories" revolutionized the biotherapeutic and pharmaceutical industry. chinese hamster ovary (cho) cells are the dominant industrial producer, especially for antibodies. human embryonic kidney cells (hek), while not being as widely used as cho cells, are used where cho cells are unable to meet the needs for expression, such as growth factors. therefore, improving recombinant protein expression from mammalian cells is a p ...201829315258
evaluation of different vector design strategies for the expression of recombinant monoclonal antibody in cho cells.monoclonal antibodies (mabs) have emerged as the most promising category of recombinant proteins due to their high efficiency for the treatment of a wide range of human diseases. the complex nature of mabs creates a great deal of challenges in both upstream and downstream manufacturing processes. proportional expression and correct folding and assembly of the light chain and heavy chain are required for efficient production of the mabs. in this regard, expression vector design has proven to have ...201829313429
ecotoxicological potential of the biocides terbutryn, octhilinone and methylisothiazolinone: underestimated risk from biocidal pathways?the use of biocides by industry, agriculture and households increased throughout the last two decades. many new applications with known substances enriched the variety of biocidal pollution sources for the aquatic environment. while agriculture was the major source for a long time, leaching from building facades and preservation of personal care and cleaning products was identified as new sources in the last few years. with the different usage forms of biocidal products the complexity of legisla ...201829306832
antidepressant drug paroxetine blocks the open pore of kv3.1 potassium patients with epilepsy, depression is a common comorbidity but difficult to be treated because many antidepressants cause pro-convulsive effects. thus, it is important to identify the risk of seizures associated with antidepressants. to determine whether paroxetine, a very potent selective serotonin reuptake inhibitor (ssri), interacts with ion channels that modulate neuronal excitability, we examined the effects of paroxetine on kv3.1 potassium channels, which contribute to highfrequency fir ...201829302214
in vitro binding and receptor-mediated activity of terlipressin at vasopressin receptors v1 and v2.terlipressin, a synthetic, systemic vasoconstrictor with selective activity at vasopressin-1 (v1) receptors, is a pro-drug for the endogenous/natural porcine hormone [lys8]-vasopressin (lvp). we investigated binding and receptor-mediated cellular activities of terlipressin, lvp, and endogenous human hormone [arg8]-vasopressin (avp) at v1 and vasopressin-2 (v2) receptors. cell membrane homogenates of chinese hamster ovary cells expressing human v1 and v2 receptors were used in competitive binding ...201829302194
blood coagulation factor x exerts differential effects on adenovirus entry into human has been proposed that blood coagulation factors, principally factor x (fx), enhance the uptake of human adenovirus type 5 (ad5) into cultured epithelial cells by bridging the viral hexon capsid protein and cell-surface heparan sulphate proteoglycans (hspgs). we studied the effects of fx on ad transduction of lymphoid cell lines (nk92mi, a natural killer cell line; daudi, a b-cell line and jurkat, a t-cell line) as well as primary peripheral blood lymphocytes (pbl) and hela epithelial cells u ...201829301346
the class i scavenger receptor cd163 promotes internalization of adamts13 by macrophages.internalization of adamts13 by macrophages may contribute to its clearance from the circulation. here we investigated endocytic mechanisms that contribute to the uptake of adamts13 by macrophages. human monocyte-derived macrophages were used to monitor the uptake of fluorescently labeled recombinant adamts13 by flow cytometry. internalization of adamts13 was blocked upon addition of the cell-permeable dynamin inhibitor dynasore. partial blocking of adamts13 uptake was observed by using mannan; h ...201729296945
targeted knock-in of an scfv-fc antibody gene into the hprt locus of chinese hamster ovary cells using crispr/cas9 and cris-pitch systems.chinese hamster ovary (cho) cells have been used as host cells for the production of pharmaceutical proteins. for the high and stable production of target proteins, the transgene should be integrated into a suitable genomic locus of host cells. here, we generated knock-in cho cells, in which transgene cassettes without a vector backbone sequence were integrated into the hprt locus of the cho genome using clustered regularly interspaced short palindromic repeats (crispr)/cas9 and crispr-mediated ...201729295784
comparative study of the effects of phosphatidylcholine rich in dha and epa on alzheimer's disease and the possible mechanisms in cho-app/ps1 cells and samp8 mice.metabolic stress induced by a high-fat (hf) diet leads to cognitive dysfunction and aging. in the present study, chinese hamster ovary cells stably transfected with amyloid precursor protein (app) and presenilin 1 (ps1) (cho-app/ps1 cells) and samp8 mice fed with an hf diet were used to study the effects of docosahexaenoic acid (dha)-enriched phosphatidylcholine (dha-pc) and eicosapentaenoic acid (epa)-enriched phosphatidylcholine (epa-pc) on alzheimer's disease (ad) and the possible mechanisms ...201829292421
evaluation of reversed-phase nano liquid chromatography conditions by using reversed-phase thin layer chromatography based on hansen solubility parameters for the analysis of amphiphilic glycosylsphingolipid transformations.pulse chase analysis is often used in investigating dynamics of cellular substances. fluorescently labeled lactosyl sphingosine molecule is useful in chasing its transformation, however the analysis of such metabolites in attomole level is of extreme difficult due to the presence of large amount of endogenous amphiphilic molecules such as glycosphingolipids, sphingomyerin, and glycerophospholipids. nano lc suites for analyzing the attomole scale metabolites, therefore removal of endogenous subst ...201829290400
antigenotoxicity properties of copaifera multijuga oleoresin and its chemical marker, the diterpene (-)-copalic view of the biological activities and growing therapeutic interest in oleoresin obtained from copaifera multijuga, this study aimed to determine the genotoxic and antigenotoxic potential of this oleoresin (cmo) and its chemical marker, diterpene (-)-copalic acid (ca). the micronucleus (mn) assay in v79 cell cultures and the ames test were used for in vitro analyses, as well as mn and comet assays in swiss mice for in vivo analyses. the in vitro genotoxicity/mutagenicity results showed that ei ...201829286884
drug-induced immune thrombocytopenia: mapping of the drug binding site to the membrane-proximal region of platelet gpix.drug-induced immune thrombocytopenia (dit) is a common complication of several medications, including commonly used antibiotics. the most widely studied dit is caused by quinine. in dit, antibodies predominantly bind to the platelet membrane glycoprotein (gp) ix in a drug-dependent fashion resulting in increased platelet clearance. binding of the sensitizing drug, such as quinine, to gpix has been proposed but is yet to be established. this work demonstrates that quinine is retained specifically ...201729286872
identification of process conditions influencing protein aggregation in chinese hamster ovary cell culture.protein aggregation of monoclonal antibodies (mabs) is a common phenomenon associated with the production of these biopharmaceuticals. these aggregates can lead to adverse side effects in patients upon administration, thus expensive downstream processing steps to remove the higher molecular weight species are inevitable. a preferable approach is to reduce the level of aggregation during bioprocessing by a careful adjustment of critical process parameters. recently, new analytical methods enabled ...201729280480
manipulation of the sodium-potassium ratio as a lever for controlling cell growth and improving cell specific productivity in perfusion cho cell cultures.perfusion processes typically require removal of a continuous or semi-continuous volume of cell culture in order to maintain a desired target cell density. for fast growing cell lines, the product loss from this stream can be upwards of 35%, significantly reducing the overall process yield. as volume removed is directly proportional to cell growth, the ability to modulate growth during perfusion cell culture production thus becomes crucial. leveraging existing media components to achieve such co ...201729278412
formation of cell membrane component domains in artificial lipid bilayer.the lipid bilayer environment around membrane proteins strongly affects their structure and functions. here, we aimed to study the fusion of proteoliposomes (pls) derived from cultured cells with an artificial lipid bilayer membrane and the distribution of the pl components after the fusion. pls, which were extracted as a crude membrane fraction from chinese hamster ovary (cho) cells, formed isolated domains in a supported lipid bilayer (slb), comprising phosphatidylcholine (pc), phosphatidyleth ...201729263355
haloacetic acid water disinfection byproducts affect pyruvate dehydrogenase activity and disrupt cellular metabolism.the disinfection of drinking water has been a major public health achievement. however, haloacetic acids (haas), generated as byproducts of water disinfection, are cytotoxic, genotoxic, mutagenic, carcinogenic, and teratogenic. previous studies of monohaa-induced genotoxicity and cell stress demonstrated that the toxicity was due to inhibition of glyceraldehyde-3-phosphate dehydrogenase (gapdh), leading to disruption of cellular metabolism and energy homeostasis. dihaas and trihaas are also prod ...201829261292
cytotoxic, antioxidative, genotoxic and antigenotoxic effects of horchata, beverage of south ecuador."horchata" is an herbal mixture infusion consumed in southern ecuador; 66% of its plants are anti-inflammatory medicinal plant, and 51% are analgesics. anti-inflammatory substances can prevent carcinogenesis mediated by cytotoxic effects and can prevent dna damage. the aim of this study was to evaluate the cytotoxicity and apoptotic/antigenotoxic effects of horchata as well as its mechanism.201729258490
synthesis, spectral characterization, antibacterial and anticancer activity of some titanium complexes.titanium complexes with and without labile groups have been synthesized by the reaction of titanium tetrachloride (ticl4) with n- containing ligands (1,2-diaminocyclohexane (dach), 1,10-phenanthroline (phen) and adamantylamine (ada), 2,2'-bipyridine (bipy), 4,4'-dimethyl-2,2'-bipyridine (bpme)) in 1:2 and 1:2:2 molar ratio respectively. the synthesized complexes have been characterized by different spectroscopic techniques i.e. elemental analysis, ft-ir, nmr (1h and 13c) and mass spectrometry. t ...201729256358
hypoxia and transforming growth factor-beta1 pathway activation promote chinese hamster ovary cell aggregation.suspension cultivation is the preferred mode of operation for the large-scale production of many biologics. chinese hamster ovary (cho) cells are anchorage-dependent in origin, but they have been widely adapted to suspension culture. in suspension culture, formation of cho cell aggregates is a common phenomenon and compromises cell culture performance in multiple ways. to better understand the underlying mechanisms that regulate cell aggregation, we utilized cho-specific transcriptome profiling ...201729251349
insights into the generation of monoclonal antibody acidic charge variants during chinese hamster ovary cell cultures.charge variation is one of the most important heterogeneities during monoclonal antibody (mab) manufacturing and this study presents insights into the generation of acidic charge variants during cell culture processes. since acidic variants generate both intracellularly and extracellularly, main charge fraction collected by weak cation exchange chromatography (wcx) was incubated in harvested cell supernatant (hcs) to simulate and investigate the extracellular process firstly. it is found that th ...201829238873
abin-1 negatively regulates μ-opioid receptor function.the μ-opioid receptor (mor) is a gi/o protein-coupled receptor that mediates analgesic, euphoric, and reward effects. using a bacterial two-hybrid screen, we reported that the carboxyl tail of the rat mor associates with a20-binding inhibitor of nuclear factor κb (abin-1). this interaction was confirmed by direct protein-protein binding and coimmunoprecipitation of mor and abin-1 proteins in cell lysates. saturation binding studies showed that abin-1 had no effect on mor binding. however, the in ...201829237725
toxicological evaluation of β-galactosidase enzyme produced by papiliotrema terrestris.β-galactosidase (ec is a glycoside hydrolase that catalyzes the release of sugar monomers from β-galactoside oligosaccharides via hydrolysis of glycosidic bonds, and has potential uses in the food industry. the safety of this enzyme and its production organism, papiliotrema terrestris (p. terrestris), are described herein. p. terrestris was non-pathogenic upon intravenous (iv) administration of 2.4 × 108 cfu and oral administration of 1.3 × 109 cfu. genotoxic results for the enzyme con ...201729233771
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