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rap1 binding to the talin 1 f0 domain makes a minimal contribution to murine platelet gpiib-iiia activation.activation of platelet glycoprotein iib-iiia (gpiib-iiia; integrin αiibβ3) leads to high-affinity fibrinogen binding and platelet aggregation during hemostasis. whereas gtp-bound rap1 gtpase promotes talin 1 binding to the β3 cytoplasmic domain to activate platelet gpiib-iiia, the rap1 effector that regulates talin association with β3 in platelets is unknown. rap1 binding to the talin 1 f0 subdomain was proposed to forge the talin 1-rap1 link in platelets. here, we report a talin 1 point mutant ...201830242097
cell culture media for recombinant protein expression in chinese hamster ovary (cho) cells: history, key components, and optimization strategies.the culture of chinese hamster ovary (cho) cells for modern industrial applications, such as expression of recombinant proteins, requires media that support growth and production. such media must support high viable cell densities while also stimulating the synthesis and extracellular transport of biologic products. early media development efforts in this area yielded basic formulations to sustain growth, viability, and cellular function, albeit comprising animal sourced components, and complex ...201830290072
construction and application of (q)sar models to predict chemical-induced in vitro chromosome aberrations.in drug development, genetic toxicology studies are conducted using in vitro and in vivo assays to identify potential mutagenic and clastogenic effects, as outlined in the international council for harmonisation (ich) s2 regulatory guideline. (quantitative) structure-activity relationship ((q)sar) models that predict assay outcomes can be used as an early screen to prioritize pharmaceutical candidates, or later during product development to evaluate safety when experimental data are unavailable ...201830278198
calibration of pertussis toxin brp batch 1 in a standardised cho cell-based clustering assay.the european pharmacopoeia (ph. eur.) pertussis toxin (pt) biological reference preparation (brp) is used as a working standard for safety testing of acellular pertussis vaccines as prescribed in the ph. eur. monographs 1356 "pertussis vaccine (acellular, component, adsorbed)" and 1595 "pertussis vaccine (acellular, co-purified, adsorbed)". the brp was calibrated in 2006 in the murine histamine sensitisation test (hist) against the world health organization (who) 1st international standard (is) ...201830272557
in vitro and in vivo evaluation of the genotoxicity of eriobotrya japonica leaf extract.eriobotrya japonica leaf is included in the chinese pharmacopoeia, and is widely used as a medicinal material in traditional medicine. the present study investigated the potential genotoxic effects of e. japonica leaf extract (eje) using three standard battery systems. genotoxicity tests were conducted following the test guidelines of the organisation for economic cooperation and development (oecd) and ministry of food and drug safety (mfds), with application of good laboratory practice. the bac ...201830268829
pharmacological characterization of the orexin/hypocretin receptor agonist nag 26.one promising series of small-molecule orexin receptor agonists has been described, but the molecular pharmacological properties, i.e. ability and potency to activate the different orexin receptor-regulated signal pathways have not been reported for any of these ligands. we have thus here assessed these properties for the most potent ligand of the series, 4'-methoxy-n,n-dimethyl-3'-[n-(3-{[2-(3-methylbenzamido)ethyl]amino}phenyl sulfamoyl]-(1,1'-biphenyl)-3-carboxamide (nag 26). chinese hamster ...201830194937
targeting of influenza viral epitopes to antigen-presenting cells by genetically engineered chimeric molecules in a humanized nod scid gamma transfer model.antiviral dna vaccines are a novel strategy in the vaccine development field, which basically consists of the administration of expression vectors coding viral antigen sequences into the host's cells. targeting of conserved viral epitopes by antibody fragments specific to activating cell surface co-receptor molecules on antigen-presenting cells could be an alternative approach for inducing protective immunity. it has been shown that fcγri on human monocytes enhances antigen presentation in vivo. ...201830191743
construction strategies for developing expression vectors for recombinant monoclonal antibody production in cho cells.recent years have seen the use of recombinant proteins in the treatment of different diseases. among them, monoclonal antibodies (mabs) are currently the fastest growing class of bio-therapeutic recombinant proteins. chinese hamster ovary (cho) cells are the most commonly used host cells for production of these recombinant mabs. expression vectors determine the expression level and quality of recombinant mabs. currently, few construction strategies for recombinant mabs expression vectors in cho ...201830191354
rational optimization of a monoclonal antibody for simultaneous improvements in its solution properties and biological activity.developability considerations should be integrated with lead engineering of antibody drug candidates in interest of their cost effective translations into medicines. to explore feasibility of this imperative, we have performed rational mutagenesis studies on a monoclonal antibody (mab1) whose development was discontinued owing to manufacturability hurdles. seven computationally designed variants of mab1 containing single point (v44k, e59s, e59t and e59y) and double (v44ke59s, v44ke59t and v44ke5 ...201830189027
evaluation of toxicological and teratogenic effects of carbosilane glucose glycodendrimers in zebrafish embryos and model rodent cell lines.glycodendrimers (glyco-ddms) represent a rapidly growing class of nanoparticles with promising properties for biomedical applications but concerns regarding the impact on human health and environment are still justified. here we report, for the first time, the comparative study of in vivo developmental toxicity of carbosilane glyco-ddms and their cytotoxicity in vitro. carbosilane glyco-ddms (generation 1-3) containing 4, 8, and 16 β-d-glucopyranosyl units at the periphery (ddm1glu, ddm2glu, and ...201830182770
ds-8500a, an orally available g protein-coupled receptor 119 agonist, upregulates glucagon-like peptide-1 and enhances glucose-dependent insulin secretion and improves glucose homeostasis in type 2 diabetic rats.g protein-coupled receptor 119 (gpr119) has been shown to be highly expressed in small intestinal l-cells and pancreatic β-cells and mediates intracellular camp concentration, glucagon-like peptide (glp-1) secretion, and glucose-stimulated insulin secretion (gsis). this study examined the pharmacological effects of 4-(5-{(1r)-1-[4-(cyclopropylcarbonyl) phenoxy]propyl}-1,2,4-oxadiazol-3-yl)-2-fluoro-n-[(2r)-1-hydroxypropan-2-yl]benzamide (ds-8500a), a novel, orally available, selective gpr119 ago ...201830217957
car-t cells based on novel bcma monoclonal antibody block multiple myeloma cell growth.the cell-surface protein b cell maturation antigen (bcma, cd269) has emerged as a promising target for car-t cell therapy for multiple myeloma. in order to create a novel bcma car, we generated a new bcma monoclonal antibody, clone 4c8a. this antibody exhibited strong and selective binding to human bcma. bcma car-t cells containing the 4c8a scfv were readily detected with recombinant bcma protein by flow cytometry. the cells were cytolytic for rpmi8226, h929, and mm1s multiple myeloma cells and ...201830208593
a biodesign approach to obtain high yields of biosimilars by anti-apoptotic cell engineering: a case study to increase the production yield of anti-tnf alpha producing recombinant cho cells.recent developments in medical biotechnology have facilitated to enhance the production of monoclonal antibodies (mabs) and recombinant proteins in mammalian cells. human mabs for clinical applications have focused on three areas, particularly cancer, immunological disorders, and infectious diseases. tumor necrosis factor alpha (tnf-α), which has both proinflammatory and immunoregulatory functions, is an important target in biopharmaceutical industry. in this study, a humanized anti-tnf-α mab pr ...201828685239
preparation and biocompatibility of crosslinked poly(3-hydroxyundecenoate).a sticky polymer, poly(3-hydroxyundecenoate) (phu), was produced by pseudomonas oleovorans when nonanoate and undecenoate were used as carbon sources. crosslinked phu (cl-phu) was prepared by heating using benzoyl peroxide as a crosslinker. according to the degree of crosslinking in the polymer, three types of cl-phu were prepared: cl-phu50, cl-phu60 and cl-phu70. fourier transform-infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry results suggested that cro ...201828867233
transcriptome-based identification of the optimal reference cho genes for normalisation of qpcr data.real-time quantitative pcr (qpcr) is the standard method for determination of relative changes in mrna transcript abundance. analytical accuracy, precision and reliability are critically dependent on the selection of internal control reference genes. in this study, the authors have identified optimal reference genes that can be utilised universally for qpcr analysis of cho cell mrnas. initially, transcriptomic datasets were analysed to identify eight endogenous genes that exhibited high expressi ...201828731643
single-step purification of recombinant gaussia luciferase from serum-containing culture medium of mammalian cells.a dihydrofolate reductase-deficient chinese hamster ovary (cho-k1/dhfr-) cell line stably expressing gaussia luciferase with a histidine-tag sequence at the carboxyl terminus (glase-his) was established. recombinant glase-his was purified from serum-containing culture medium by single-step ni-chelate column chromatography in the presence of 2 m nacl and 0.01% tween 20. the protein yield of glase-his with over 95% purity was 0.5 mg from 0.9 l of the cultured medium. the enzymatic properties of pu ...201828888757
v79 fibroblasts are protected against reactive oxygen species by flax fabric.chinese hamster pulmonary fibroblasts (v79 cells) pre-treated with flax fabrics derived from non-modified or genetically engineered flax fibres and treated with h2o2 revealed a markedly lower level of intracellular reactive oxygen species (ros) than control, non-pre-treated cells. the fabrics were prepared from fibres derived from two kinds of transgenic plants: w92 plants, which overproduce flavonoids, and m type plants, which produce hydroxybutyrate polymer in their vascular bundles and thus i ...201828689336
phosphorylation of extracellular signal-regulated kinase as a biomarker for cannabinoid receptor 2 activation.cannabinoid receptor 2 (cb2r) is a therapeutic target in inflammatory diseases; its activation by agonists provides important clinical information, but there are currently no methods to quantify cb2r activation in humans. chinese hamster ovary (cho)-k1 cells and mouse and human whole blood cells were used for experiments. cb2r was activated in cells by treatment with the agonist cp55,940. cells were also pretreated with proprietary compound a and b (experimental agonists). we developed our metho ...201830450437
binding characteristics of two oxytocin variants and vasopressin at oxytocin receptors from four primate species with different social behavior patterns.a clade of new world monkeys (nwms) exhibits considerable diversity in both oxytocin (ot) ligand and oxytocin receptor (otr) structure. most notable is the variant pro8-ot, with proline instead of leucine at the eighth position, resulting in a rigid bend in the peptide backbone. a higher proportion of species that express pro8-ot also engage in biparental care and social monogamy. when marmosets (genus callithrix), a biparental and monogamous pro8-ot nwm species, are administered the ancestral l ...201830068728
defective mucin-type glycosylation on α-dystroglycan in cog-deficient cells increases its susceptibility to bacterial proteases.deficiency in subunits of the conserved oligomeric golgi (cog) complex results in pleiotropic defects in glycosylation and causes congenital disorders in humans. insight regarding the functional consequences of this defective glycosylation and the identity of specific glycoproteins affected is lacking. a chemical glycobiology strategy was adopted to identify the surface glycoproteins most sensitive to altered glycosylation in cog-deficient chinese hamster ovary (cho) cells. following metabolic l ...201830049793
exposure to solar light reduces cytotoxicity of sewage effluents to mammalian cells: roles of reactive oxygen and nitrogen species.sewage effluents can contain hundreds of toxic pollutants, making them a risk to humans when involved in drinking water. it is therefore important to evaluate the cytotoxicity of sewage effluents to mammalian cells. solar light might influence the water quality of sewage effluents after their discharge into lakes or rivers, altering their cytotoxicity. in this study, natural solar light was found to lower the cytotoxicity of sewage effluents to chinese hamster ovary (cho) cells. cytotoxicity of ...201830015097
detection of tiger podoplanin using the anti-cat podoplanin monoclonal antibody pmab-52.podoplanin (pdpn) is expressed in type i alveolar cells of lung but not in type ii alveolar cells. pdpn is also known as a specific lymphatic endothelial cell marker because pdpn is not expressed in vascular endothelial cells. pdpns of several animals have been characterized using specific anti-pdpn monoclonal antibodies (mabs): pmab-1, pmab-2, pmab-32, pmab-38, pmab-44, and pmab-52 for mouse, rat, rabbit, dog, bovine, and cat pdpns, respectively. in this study, we investigated the possible cros ...201830362928
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
functional characterization of oligopeptide transporter 1 of dairy cows.it 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
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
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
melanin nanoparticles: antioxidant activities and effects on γ-ray-induced dna damage in the mouse.the radioprotective and antioxidant activities of melanin nanoparticles (mnp) were investigated in chinese hamster ovary (cho) cells in vitro and balb/c mice in vivo. the endpoints measured were cell viability, superoxide dismutase (sod) enzyme activity, malondialdehyde (mda) levels, dna damage (comet assay), and histopathological examination of tissues. irradiated groups showed decreased sod activity and increased mda levels. irradiation caused a 3-10-fold increase in comet parameters such as % ...201829555060
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
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
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
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
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
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
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 channel.in 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 lymphocytes.it 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
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 rutin.in 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
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 acid.in 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
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
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
distinctive binding properties of the negative allosteric modulator, [3h]sb269,652, at recombinant dopamine d3 receptors.recently, employing radioligand displacement and functional coupling studies, we demonstrated that sb269,652 (n-[(1r,4r)-4-[2-(7-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-1h-indole-2-carboxamide) interacts in an atypical manner with dopamine d3 receptor displaying a unique profile reminiscent of a negative allosteric ligand. here, we characterized the binding of radiolabelled [3h]sb269,652 to human dopamine d3 receptor stably expressed in chinese hamster ovary cells. under satur ...201829223348
amp and adenosine are both ligands for adenosine 2b receptor signaling.adenosine is considered the canonical ligand for the adenosine 2b receptor (a2br). a2br is upregulated following kidney ischemia augmenting post ischemic blood flow and limiting tubular injury. in this context the beneficial effect of a2br signaling has been attributed to an increase in the pericellular concentration of adenosine. however, following renal ischemia both kidney adenosine monophosphate (amp) and adenosine levels are substantially increased. using computational modeling and calcium ...201829191553
role of 6-o-α-maltosyl-β-cyclodextrin in lysosomal cholesterol deprivation in npc1-deficient chinese hamster ovary cells.we aimed to investigate whether 6-o-α-maltosyl-β-cyclodextrin (mal-βcd) is incorporated into cells and lysosomes during the release of unesterified cholesterol in npc1-deficient chinese hamster ovary (cho) cells (npc1 ko cells) and cho-jp17 cells (jp17 cells). internalization of mal-βcd in cells and lysosomes and extracellular release of lysosomal unesterified cholesterol were demonstrated by lc/ms/ms and lc/ms, respectively. internalization of mal-βcd was greater in npc1 ko cells than in jp17 c ...201829172126
proteomic analysis of cho cell lines producing high and low quantities of a recombinant antibody before and after selection with methotrexate.high levels of recombinant protein production in chinese hamster ovary (cho) cells can be achieved by amplification of transgenes using the dihydrofolate reductase/methotrexate (dhfr/mtx) system. with the aim to identify predictive markers enabling the preselection of suitable high producing clones we investigated the impact of mtx-based gene amplification on two cho cells lines producing different levels of a human monoclonal antibody by carrying out a comparative proteome analysis. the differe ...201829137976
dietary k+ and cl- independently regulate basolateral conductance in principal and intercalated cells of the collecting duct.the renal collecting duct contains two distinct cell types, principal and intercalated cells, expressing potassium kir4.1/5.1 (kcnj10/16) and chloride clc-k2 (clc-kb in humans) channels on their basolateral membrane, respectively. both channels are thought to play important roles in controlling systemic water-electrolyte balance and blood pressure. however, little is known about mechanisms regulating activity of kir4.1/5.1 and clc-k2/b. here, we employed patch clamp analysis at the single channe ...201829134279
using specific recombinant gonadotropins to induce spermatogenesis and spermiation in the european eel (anguilla anguilla).new specific european eel (anguilla anguilla) recombinant gonadotropins (aargths) produced in the ovarian cells of chinese hamsters (cho) were used to induce maturation in captive male eels. in the first experiment, five different hormonal treatments were assayed: one group was given a constant dose of recombinant european eel follicle-stimulating hormone (aarfsh; 4 μg/fish) for 9 weeks, and the second group received a constant dose of recombinant european eel luteinizing hormone (aarlh; 2 μg/fi ...201829120707
tolerability, response and outcome of high-risk neuroblastoma patients treated with long-term infusion of anti-gd2 antibody ch14.18/cho.immunotherapy with short term infusion (sti) of monoclonal anti-gd2 antibody (mab) ch14.18 (4 × 25 mg/m2/d; 8-20 h) in combination with cytokines and 13-cis retinoic acid (ra) prolonged survival in high-risk neuroblastoma (nb) patients. here, we investigated long-term infusion (lti) of ch14.18 produced in chinese hamster ovary cells (ch14.18/cho; 10 × 10 mg/m2; 24 h) in combination with subcutaneous (s.c.) interleukin-2 (il-2) in a single center program and report clinical response, toxicity and ...201829120699
functional characterization of the dual allatostatin-a receptors in mosquitoes.the neuropeptide allatostatin-a (asta) and its cognate receptors (astars) are involved in the modulation of feeding behavior, which in hematophagous insects includes the regulation of the disease vector-related behaviors, host seeking and blood feeding. in mosquitoes and other dipterans, there are two copies of astar, contrasting with the single copy found in other insects. in this study, we identified and cloned the dual astar system of two important disease vectors aedes aegypti and culex quin ...201829103918
chemical characterization and cytotoxic, genotoxic, and mutagenic properties of baccharis trinervis (lam, persoon) from colombia and brazil.baccharis trinervis (lam, persoon) leaves are used in the traditional medicine for the treatment of high fevers, edema, inflammation, sores and muscle cramps, snakebites and as antiseptic.201829100934
identification of a potent mar element from the human genome and assessment of its activity in stably transfected cho cells.low-level and unstable transgene expression are common issues using the cho cell expression system. matrix attachment regions (mars) enhance transgene expression levels, but additional research is needed to improve their function and to determine their mechanism of action. mar-6 from cho chromosomes actively mediates high and consistent gene expression. in this study, we compared the effects of two new mars and mar-6 on transgene expression in recombinant cho cells and found one potent mar eleme ...201829077269
combinations of chromosome transfer and genome editing for the development of cell/animal models of human disease and humanized animal models.chromosome transfer technology, including chromosome modification, enables the introduction of mb-sized or multiple genes to desired cells or animals. this technology has allowed innovative developments to be made for models of human disease and humanized animals, including down syndrome model mice and humanized transchromosomic (tc) immunoglobulin mice. genome editing techniques are developing rapidly, and permit modifications such as gene knockout and knockin to be performed in various cell li ...201829180645
regulatory role of mir-18a to ccn2 by tgf-β1 signaling pathway in pulmonary injury induced by nano-sio2.this research is designed to investigate the regulatory effect of mir-18a to the target gene connective tissue growth factor (ctgf, or ccn2), by participating in tgf-β1 signaling pathway and explore the pathogenic mechanism of mir-18a in pulmonary injury induced by nano-sio2 based on our early study. mir-18a and expression of tgf-β1 in chinese hamster lung (chl) fibroblasts cells stimulated by supernatants of nr8383 cells exposed to 40 μg/ml nano-sio2 for 24 h demonstrated 1.58 ± 0.22-fold and 1 ...201829067610
z-505 hydrochloride ameliorates chemotherapy-induced anorexia in rodents via activation of the ghrelin receptor, ghsr1a.despite its therapeutic advantages, chemotherapy with anti-cancer drugs can cause adverse effects, including anorexia and weight loss. although most patients with cancer suffer from anorexia during chemotherapy, resulting in the need to suspend or cease treatment and thereby worsening prognosis, treatment options for anorexia remain limited. ghrelin is an orexigenic hormone that has been proposed to prevent anorexia. to investigate the potential of ghrelin receptor agonists, synthetic small-mole ...201829066414
ca2+ -dependent down-regulation of human histamine h1 receptors in chinese hamster ovary cells.gq/11 protein-coupled human histamine h1 receptors in chinese hamster ovary cells stimulated with histamine undergo clathrin-dependent endocytosis followed by proteasome/lysosome-mediated down-regulation. in this study, we evaluated the effects of a sustained increase in intracellular ca2+ concentrations induced by a receptor-bypassed stimulation with ionomycin, a ca2+ ionophore, on the endocytosis and down-regulation of h1 receptors in chinese hamster ovary cells. all cellular and cell-surface ...201829063596
types of cell death and apoptotic stages in chinese hamster ovary cells distinguished by raman spectroscopy.cell death is the ultimate cause of productivity loss in bioreactors that are used to produce therapeutic proteins. we investigated the ability of raman spectroscopy to detect the onset and types of cell death for chinese hamster ovary (cho) cells-the most widely used cell type for therapeutic protein production. raman spectroscopy was used to compare apoptotic, necrotic, autophagic, and control cho cells. several specific nucleic acid-, protein-, and lipid-associated marker bands within the 650 ...201829030978
kinetic characterization of bile salt transport by human ntcp (slc10a1).the transport of bile acids facilitated by ntcp is an important factor in establishing bile flow. in this study, we examine the kinetics associated with human ntcp-dependent transport of two quantitatively important bile acids comprising the human bile acid pool, chenodeoxycholic acid and glycine-chenodeoxycholate, and secondary bile salt, 3-sulfo-glycolithocholate of potential toxicological significance. the study employed human ntcp overexpressing chinese hamster ovary cells and results compar ...201829024779
manufacturing history of etanercept (enbrel®): consistency of product quality through major process revisions.etanercept (etn) (enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (tnf), a proinflammatory cytokine. etn is synthesized in chinese hamster ovary cells by recombinant dna technology as a fusion protein, with a fully human tnfrii ectodomain linked to the fc portion of human igg1. successful manufacture of biologics, such as etn, requires sophisticated process and product understanding, as well as meticulous control of operations to maintain product con ...201829020515
two-dimensional gel electrophoresis and 2d-dige.two-dimensional polyacrylamide gel electrophoresis (2d-page) continues to be one of the most versatile and widely used techniques to study the proteome of a biological system. in particular, a modified version of 2d-page, two-dimensional difference gel electrophoresis (2d-dige), which uses differential labeling of protein samples with up to three fluorescent tags, offers greater sensitivity and reproducibility over conventional 2d-page gels for differential quantitative analysis of protein expre ...201829019120
serological and molecular investigation of 2117-like vesiviruses in cats.vesivirus 2117 was first discovered as a contaminant in chinese hamster ovary (cho) cell cultures used for human drug production. similar vesiviruses (vevs) have been detected recently in dogs. in order to address the hypothesis that cats may also be exposed to 2117-like vevs, in this study, we screened 236 feline sera using an enzyme-linked immunosorbent assay (elisa) based on a recombinant vp1 protein from the canine vev bari/212/07/ita. igg antibodies against the 2117-like vev were detected i ...201829022118
evaluation of genotoxicity and subchronic toxicity of the standardized leaves infusion extract of copaifera malmei harms in experimental models.copaifera malmei harms (fabaceae), known mainly as óleo-mirim, is a native and endemic plant found in the states of mato grosso and goiás of brazil. the plant's leaves infusion is popularly used by riverine communities of the northern araguaia microregion, mato grosso, brazil, for the treatment of gastric ulcers and inflammatory diseases of the respiratory tract. the gastric antiulcer activity of the standardized leaves infusion extract of copaifera malmei (siecm) in rodents has been reported. t ...201828943446
high frequency electroporation efficiency is under control of membrane capacitive charging and voltage potential relaxation.the study presents the proof of concept for a possibility to achieve a better electroporation in the mhz pulse repetition frequency (prf) region compared to the conventional low frequency protocols. the 200ns×10 pulses bursts of 10-14kv/cm have been used to permeabilize chinese hamster ovary (cho) cells in a wide range (1hz-1mhz) of prf. the permeabilization efficiency was evaluated using fluorescent dye assay (propidium iodide) and flow cytometry. it was determined that a threshold prf exists w ...201828922628
exploring cellular behavior under transient gene expression and its impact on mab productivity and fc-glycosylation.transient gene expression (tge) is a methodology employed in bioprocessing for the fast provision of recombinant protein material. mild hypothermia is often introduced to overcome the low yield typically achieved with tge and improve specific protein productivity. it is therefore of interest to examine the impact of mild hypothermic temperatures on both the yield and quality of transiently expressed proteins and the relationship to changes in cellular processes and metabolism. in this study, we ...201828921534
karyotype variation of cho host cell lines over time in culture characterized by chromosome counting and chromosome painting.genomic rearrangements are a common phenomenon in rapidly growing cell lines such as chinese hamster ovary (cho) cells, a feature that in the context of production of biologics may lead to cell line and product instability. few methods exist to assess such genome wide instability. here, we use the population distribution of chromosome numbers per cell as well as chromosome painting to quantify the karyotypic variation in several cho host cell lines. cho-s, cho-k1 8 mm glutamine, and cho-k1 cells ...201828921524
fed-batch cho cell culture for lab-scale antibody production.fed-batch culture is the most commonly used upstream process in industry today for recombinant monoclonal antibody production using chinese hamster ovary (cho) cells. developing and optimizing this process in the lab is crucial for establishing process knowledge, which enables rapid and predictable tech-transfer to manufacturing scale. in this chapter, we describe stepwise how to carry out fed-batch cho cell culture for lab-scale antibody production.201828921435
pharmacokinetics, safety and efficacy of a recombinant factor ix product, trenonacog alfa in previously treated haemophilia b patients.trenonacog alfa (ib1001) is a recombinant factor ix (rfix) manufactured in chinese hamster ovary (cho) cells. ib1001 was evaluated in a multicentre clinical trial with haemophilia b patients.201828833808
heparan sulfate proteoglycan deficiency up-regulates the intracellular production of nitric oxide in chinese hamster ovary cell lines.we investigated the role of glycosaminoglycans (gags) in the regulation of endothelial nitric oxide synthase (enos) activity in wild-type cho-k1 cells and in xylosyltransferase-deficient cho-745 cells. gags inhibit the integrin/fak/pi3k/akt signaling pathway in cho-k1 cells, decreasing the phosphorylation of enos at ser1177. furthermore, in cho-k1 cells, enos and pkcα are localized at sphingolipid- and cholesterol-rich domains in the plasma membrane called caveolae. at caveolae, pkcα activation ...201828833096
whole-genome sequencing of invasion-resistant cells identifies laminin α2 as a host factor for bacterial invasion.to understand the role of glycosaminoglycans in bacterial cellular invasion, xylosyltransferase-deficient mutants of chinese hamster ovary (cho) cells were created using clustered regularly interspaced short palindromic repeat (crispr) and crispr-associated gene 9 (crispr-cas9) gene targeting. when these mutants were compared to the pgsa745 cell line, a cho xylosyltransferase mutant generated previously using chemical mutagenesis, an unexpected result was obtained. bacterial invasion of pgsa745 ...201728074024
design and characterization of plasmids encoding antigenic peptides of aha1 from aeromonas hydrophila as prospective fish vaccines.the current investigation aimed at designing dna vaccines against aeromonas hydrophila infections. the dna vaccine candidates were designed to express two antigenic outer membrane protein (aha1) peptides and to be delivered by a nanoparticle-based delivery system. gene sequences of conserved regions of antigenic aha1 [aha1(211-381), aha1(211-381)opt, aha1(703-999) and aha1(703-999)opt] were cloned into pvax-gfp expression vector. the selected dna vaccine candidates were purified from e. coli dh5 ...201727899335
glycan region of gpi anchored-protein is required for cytocidal oligomerization of an anticancer parasporin-2, cry46aa1 protein, from bacillus thuringiensis strain a1547.parasporin-2 (ps2), alternatively named cry46aa1, an anticancer protein derived from bacillus thuringiensis strain a1547, causes specific cell damage via ps2 oligomerization in the cell membrane. although ps2 requires glycosylphosphatidylinositol (gpi)-anchored proteins for its cytocidal action, their precise role is unknown. here, we report that the glycan of gpi induces ps2 oligomerization, which causes cell death. cytotoxicity, cell-binding and oligomerization of the toxin were not observed i ...201727863961
in vitro antimicrobial and cytotoxic effects of anacardium occidentale and mangifera indica in oral care.oral health is an integral and important component of general health. infectious diseases such as caries, periodontal, and gingivitis indicate the onset of imbalance in homeostasis between oral micro biota and host. the present day medicaments used in oral health care have numerous side effects. the uses of herbal plants as an alternative have gained popularity due to side effects of antibiotics and emergence of multidrug resistant strains. anacardium occidentale (cashew) and mangifera indica (m ...201725709341
stable high-level expression of factor viii in chinese hamster ovary cells in improved elongation factor-1 alpha-based system.recombinant factor viii (fviii), used for haemophilia a therapy, is one of the most challenging among the therapeutic proteins produced in heterologous expression systems. deletion variant of fviii, in which the entire domain b is replaced by a short linker peptide, was approved for medical use. efficacy and safety of this fviii deletion variant are similar to full-length fviii preparations while the level of production in cho cells is substantially higher. typical levels of productivity for cho ...201728340620
matrix attachment region combinations increase transgene expression in transfected chinese hamster ovary cells.matrix attachment regions (mars) are cis-acting dna elements that can increase transgene expression levels in a cho cell expression system. to investigate the effects of mar combinations on transgene expression and the underlying regulatory mechanisms, we generated constructs in which the enhanced green fluorescent protein (egfp) gene flanked by different combinations of human β-interferon and β-globin mar (imar and gmar, respectively), which was driven by the cytomegalovirus (cmv) or simian vir ...201728216629
a scalable lysyl hydroxylase 2 expression system and luciferase-based enzymatic activity assay.hydroxylysine aldehyde-derived collagen cross-links (hlccs) accumulate in fibrotic tissues and certain types of cancer and are thought to drive the progression of these diseases. hlcc formation is initiated by lysyl hydroxylase 2 (lh2), an fe(ii) and α-ketoglutarate (αkg)-dependent oxygenase that hydroxylates telopeptidyl lysine residues on collagen. development of lh2 antagonists for the treatment of these diseases will require a reliable source of recombinant lh2 protein and a non-radioactive ...201728216326
parameter estimation in large-scale systems biology models: a parallel and self-adaptive cooperative strategy.the development of large-scale kinetic models is one of the current key issues in computational systems biology and bioinformatics. here we consider the problem of parameter estimation in nonlinear dynamic models. global optimization methods can be used to solve this type of problems but the associated computational cost is very large. moreover, many of these methods need the tuning of a number of adjustable search parameters, requiring a number of initial exploratory runs and therefore further ...201728109249
cellular engineering for therapeutic protein production: product quality, host modification, and process improvement.recombinant proteins offer many therapeutic advantages unavailable in traditional small molecule drugs, but the need for cellular versus chemical synthesis complicates production. avenues for producing therapeutic biologics are continuously expanding, and developments in biochemistry, cell biology, and bioengineering fuel new discoveries that promise safer, more efficient, and cheaper drugs for consumers. numerous approaches to express recombinant proteins exist, but escherichia coli, saccharomy ...201727933725
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