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structure-activity relationship studies of antiplasmodial cyclometallated ruthenium(ii), rhodium(iii) and iridium(iii) complexes of 2-phenylbenzimidazoles.benzimidazoles, such as albendazole, thiabendazole and omeprazole have antiplasmodial activity against plasmodium falciparum and are widely used as scaffolds for metal-based drug research. incorporating substituents with various lipophilic and electronic properties can influence trans-membrane interactions and concomitantly improve the biological activity. to study structure-activity relationships, a series of 2-phenylbenzimidazoles and their corresponding ru(ii), ir(iii) and rh(iii) cyclometall ...201930342422
whole synthetic pathway engineering of recombinant protein production.the output from protein biomanufacturing systems is a function of total host cell biomass synthetic capacity and recombinant protein production per unit cell biomass. in this study, we describe how these two properties can be simultaneously optimized via design of a product-specific combination of synthetic dna parts to maximize flux through the protein synthetic pathway and the use of a host cell chassis with an increased capability to synthesize both cell and product biomass. using secreted al ...201930345502
a new highly thyrotropin receptor-selective small-molecule antagonist with potential for the treatment of graves' orbitopathy.the thyrotropin receptor (tshr) is the target for autoimmune thyroid stimulating antibodies (tsab) triggering hyperthyroidism. whereas elevated thyroid hormone synthesis by the thyroid in graves' disease can be treated by antithyroid agents, for the pathogenic activation of tshr in retro-orbital fibroblasts of the eye, leading to graves' orbitopathy (go), no causal tshr directed therapy is available.201930351237
bioprocess development of antibody-drug conjugate production for cancer treatment.antibody-drug conjugate (adc) is a class of targeted cancer therapies that combine the advantages of monoclonal antibody (mab)'s specific targeting and chemotherapy's potent cytotoxicity. the therapeutic effect of adc is significantly affected by its bioproduction process. this study aims to develop an effective adc production process using anti-her2 mab-drug as a model therapeutic. first, a high titer (>2 g/l) of mab was produced by chinese hamster ovary cells from fed-batch cell culture. both ...201830352095
initial hazard assessment of benzyl salicylate: in vitro genotoxicity test and combined repeated-dose and reproductive/developmental toxicity screening test in rats.benzyl salicylate is used as a fragrance ingredient and an ultraviolet light absorber, but its toxicity is unknown. therefore, toxicity tests and hazard classification were conducted for screening assessment under the japanese chemical substances control law. benzyl salicylate was found to be non-genotoxic in vitro based on the chromosomal aberration test using chinese hamster lung cells. however, the combined repeated-dose and reproductive/developmental screening toxicity test, in which male an ...201830359701
tetrandrine, a novel inhibitor of ether-à-go-go-1 (eag1), targeted to cervical cancer development.mortality-to-incidence ratios in patients with cancer are extremely high, positioning cancer as a major cause of death worldwide. ether-à-go-go-1 (eag1) is an ion channel that plays important roles in tumour proliferation, malignant transformation, invasion, metastasis, recurrence, and prognosis. therefore, identifying potent and specific eag1 channel inhibitors is crucial. in this study, we identified the first natural inhibitor of eag1, the traditional chinese medicine agent tetrandrine, and e ...201930362536
establishment of p38bf, a core-fucose-deficient mouse-canine chimeric antibody against dog podoplanin.podoplanin (pdpn), a type i transmembrane sialoglycoprotein, is expressed in normal tissues, including lymphatic endothelial cells, pulmonary type i alveolar cells, and renal podocytes. the overexpression of pdpn in cancers is associated with hematogenous metastasis by interactions with the c-type lectin-like receptor 2 (clec-2). we have previously reported the development of a mouse monoclonal antibody (mab) clone, pmab-38 (igg1, kappa), against dog pdpn (dpdpn). pmab-38 reacted strongly with c ...201830362926
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
the augmenting effects of the tdna insulator on stable expression of monoclonal antibody in chinese hamster ovary cells.cell line development is one of the most critical steps in the production of complex recombinant therapeutic proteins such as monoclonal antibodies in mammalian cells. generation of industrial cell lines is mainly based on the time-consuming and laborious process of selection and screening of a large number of clones. with the increasing demand for therapeutic proteins during the past years, more effort is invested to improve the efficiency of cell line development. in line with this premise, se ...201830362930
establishment of monoclonal antibody pmab-202 against horse podoplanin.podoplanin (pdpn), a type i transmembrane glycoprotein, is expressed in several body tissues, including podocytes of renal glomerulus, type i alveolar cells of lung, and lymphatic endothelial cells. pdpn activates platelet aggregation by binding to c-type lectin-like receptor-2 (clec-2) presented on platelets. monoclonal antibodies (mabs) against human-, mouse-, rat-, rabbit-, dog-, bovine-, and cat-pdpn have already been established. however, anti-horse pdpn mabs have not yet been developed. in ...201830362932
at-line raman spectroscopy and design of experiments for robust monitoring and control of miniature bioreactor cultures.the biopharmaceutical industry is moving toward a more quality by design (qbd) approach that seeks to increase product and process understanding and process control. miniature bioreactor systems offer a high-throughput method enabling the assessment of numerous process variables in a controlled environment. however, the number of off/at-line samples that can be taken is restricted due to the small working volume of each vessel. this limitation may be resolved through the use of raman spectroscop ...201930378770
purification of recombinant human butyrylcholinesterase on hupresin®.affinity chromatography on procainamide-sepharose has been an important step in the purification of butyrylcholinesterase (bche) and acetylcholinesterase (ache) since its introduction in 1978. the procainamide affinity gel has limitations. in the present report a new affinity gel called hupresin® was evaluated for its ability to purify truncated, recombinant human butyrylcholinesterase (rhubche) expressed in a stably transfected chinese hamster ovary cell line. we present a detailed example of t ...201830384187
toxicological assessment of xanthigen® nutraceutical extract combination: mutagenicity, genotoxicity and oral toxicity.xanthigen® is a nutraceutical combination for weight management capable of increasing energy expenditure via uncoupling protein 1 (ucp-1) in white adipose tissue. it consists of brown seaweed undaria pinnatifida extract, rich in the carotenoid fucoxanthin (fx) and pomegranate seed oil (pso), rich in punicic acid. xanthigen was screened to determine its genotoxicity and 90-days repeated oral toxicity. genotoxicity was assessed with the ames test (ta89, ta100, ta1535, ta1537, wp2), chromosomal abe ...201830386730
mutagenic activity of n-nitrosodiethylamine in cell lines expressing human cyp2e1-adequacy of dimethylsulfoxide as solvent.human cyp2e1 metabolizes many xenobiotics of low-molecular weight, thereby activating various promutagens/procarcinogens. in toxicological studies in vitro, dimethylsulfoxide (dmso) is a common vehicle for organic compounds. however, it was observed to potently inhibit cyp2e1 activity. we were interested in whether it affects cyp2e1-dependent mutagenic responses. in this study, n-nitrosodiethylamine (ndea), which is soluble in both water and dmso, was used as a model promutagen. it induced hprt ...201930387191
revealing key determinants of clonal variation in transgene expression in recombinant cho cells using targeted genome editing.generation of recombinant chinese hamster ovary (rcho) cell lines is critical for the production of therapeutic proteins. however, the high degree of phenotypic heterogeneity among generated clones, referred to as clonal variation, makes the rcho cell line development process inefficient and unpredictable. here, we investigated the major genomic causes of clonal variation. we found the following: (1) consistent with previous studies, a strong variation in rcho clones in response to hypothermia ( ...201830388888
influence of chromatin remodeling in the removal of uvc-induced damage in tcr proficient and deficient chinese hamster cells.in mammalian cells, nucleotide excision repair system is constituted of two sub-pathways, global genomic repair (ggr) and transcription coupled repair (tcr). deficiency of tcr pathway leads to cockyane syndrome (cs) which is a rare human autosomal recessive disorder. owing to the pivotal role of csb gene in tcr, it's mutation causes severe repair and transcriptional defects in csb patients. csb protein belongs to the atp chromatin remodeling complex, hence presumably an improper chromatin remode ...201830389155
depletion of endogenous mirna-378-3p increases peak cell density of cho dp12 cells and is correlated with elevated levels of ubiquitin carboxyl-terminal hydrolase 14.mirnas are potent molecular regulators of cellular behaviour. the manipulation of these small non-coding rnas has been used to enhance industrially relevant phenotypes in chinese hamster ovary (cho) cells. we investigated the stable depletion of six mirnas; mir-204-5p, 338-3p, 378-3p, 409-3p, 455-3p and 505-3p, robustly associated with cell growth rate from a previous profiling study. inhibition of endogenous mir-378-3p function by mirna-sponge-decoy improved peak cell density by 59%. quantitati ...201830389639
an alternative exon of caps2 influences catecholamine loading into ldcvs of chromaffin cells.the calcium-dependent activator proteins for secretion (caps) are priming factors for synaptic and large dense-core vesicles (ldcvs), promoting their entry into and stabilizing the release-ready state. a modulatory role of caps in catecholamine loading of vesicles has been suggested. although an influence of caps on monoamine transporter function and on vesicle acidification has been reported, a role of caps in vesicle loading is disputed. using expression of naturally occurring splice variants ...201930389842
glucagon-related peptides from phylogenetically ancient fish reveal new approaches to the development of dual gcgr and glp1r agonists for type 2 diabetes therapy.the insulinotropic and antihyperglycaemic properties of glucagons from the sea lamprey (petromyzontiformes), paddlefish (acipenseriformes) and trout (teleostei) and oxyntomodulin from dogfish (elasmobranchii) and ratfish (holocephali) were compared with those of human glucagon and glp-1 in mammalian test systems. all fish peptides produced concentration-dependent stimulation of insulin release from brin-bd11 rat and 1.1 b4 human clonal β-cells and isolated mouse islets. paddlefish glucagon was t ...201830391422
genotoxicity of three biofuel candidates compared to reference fuels.global demand for alternative energy sources increases due to concerns regarding energy security and greenhouse gas emissions. however, little is known regarding the impacts of biofuels to the environment and human health even though the identification of such impacts is important to avoid biofuels leading to undesired effects. in this study mutagenicity and genotoxicity of the three biofuel candidates ethyl levulinate (el), 2-methyltetrahydrofuran (2-mthf) and 2-methylfuran (2-mf) were investig ...201830391874
efficient development of stable recombinant chinese hamster ovary (rcho) cell lines to produce antibodies by using dimethyl sulfoxide (dmso) in electroporation.development of stable rcho cell lines is still time consuming and labor intensive, although it is a critical step in the commercial development of recombinant antibodies. the current work demonstrates, for the first time, that electroporation of cho cells with dmso can enhance stable expression of recombinant antibodies in rcho cells. electroporation with dmso resulted in an average 3.7-fold and 2.8-fold increases in expression levels of aflibercept and pembrolizumab, respectively, in pools of s ...201930394043
the treatment effect of novel hghrh homodimer to male infertility hamster.extra-hypothalamic growth hormone-releasing hormone (ghrh) plays an important role in reproduction. to study the treatment effect of grin (a novel hghrh homodimer), the infertility models of 85 male chinese hamsters were established by intraperitoneally injecting 20 mg/kg of cyclophosphamide once in a week for 5 weeks and the treatment with grin or human menopausal gonadotropin (hmg) as positive control was evaluated by performing a 3-week mating experiment. 2-8 mg/kg of grin and 200 u/kg of hmg ...201830402024
genotoxicity evaluation of an ethanol extract mixture of astragali radix and salviae miltiorrhizae radix.myelophil, a combination of astragali radix and salviae radix, is one of the most commonly used remedies for disorders of qi and blood in traditional chinese medicine. based on the clinical applications of these plants, in particular to pregnant woman, this study aimed to evaluate the genotoxic potential of an ethanol extract mixture of the above two herbs, called myelophil. following the organization for economic cooperation and development (oecd) guideline methods, a genotoxicity test was cond ...201830402128
cell surface proteoglycan-mediated uptake and accumulation of the alzheimer's disease peptide aβ(1-42).proteoglycans (pgs) have been found in alzheimer's disease amyloid-β (aβ) plaques and their glycosaminoglycan chains reportedly influence aβ aggregation, neurotoxicity and intracellular accumulation in cell and animal models, but their exact pathophysiological role(s) remain unclear. we have studied the cellular uptake of fluorescently labelled aβ(1-42) and aβ(1-40) peptides in normal cho cells (k1) and the mutant cell line (pgsa-745) which lacks all protein-attached heparan and chondroitin sulf ...201830409516
process development for an inducible rituximab-expressing chinese hamster ovary cell line.inducible mammalian expression systems are becoming increasingly available and are not only useful for the production of cytotoxic/cytostatic products, but also confer the unique ability to uncouple the growth and production phases. in this work, we have specifically investigated how the cell culture state at the time of induction influences the cumate-inducible expression of recombinant rituximab by a gs-cho cell line. to this end, cells grown in batch and fed-batch cultures were induced at inc ...201930414355
domain unfolding of monoclonal antibody fragments revealed by non-reducing sds-page.monoclonal antibodies and derived fragments are used extensively both experimentally and therapeutically. thorough characterization of such antibodies is necessary and includes assessment of their thermal and storage stabilities. thus, assessment of the underlying conformational stabilities of the antibodies is also important. we recently documented that non-reducing sds-page can be used to assess both monoclonal and polyclonal igg domain thermal unfolding in sds. utilizing this same h2e2 anti-c ...201830417132
proline 36 of the factor xiii activation peptide plays a crucial role in substrate recognition and zymogen activation.the activation peptide of blood coagulation factor xiii (ap-fxiii) has important functions in stabilizing the fxiii-a2 dimer and regulating fxiii activation. contributions of many of its 37 amino acids to these functions have been described. however, the role of proline 36, which is adjacent to the thrombin cleavage site at arg37, has not yet been studied in detail. we approached this question when we came across a patient with congenital fxiii deficiency in whom we detected a novel pro36ser mut ...201830419598
effective bioreactor ph control using only sparging gases.ph control is critical in bioreactor operations, typically realized through a two-sided control loop, where co2 sparging and base addition are used in bicarbonate-buffered media. though a common approach, base addition could compromise culture performance due to the potential impact from ph excursions and osmolality increase in large-scale bioreactors. in this study, the feasibility of utilizing control of sparge gas composition as part of the ph control loop was assessed in chinese hamster ovar ...201930421525
combined effects of glycosylation precursors and lactate on the glycoprofile of igg produced by cho cells.the glycosylation profile of therapeutic monoclonal antibodies (mabs) is a crucial quality parameter for industrial immunoglobulin g (igg) production. several alternative carbon sources, which function as glycosylation precursors, have been reported to impact the glycosylation pattern. since the cells give priority to glucose uptake, the presence of this substrate can lower the effects of alternative sugars on the glycosylation. in order to get a better understanding of the influence of alternat ...201930423367
histone tails decrease n7-methyl-2'-deoxyguanosine depurination and yield dna-protein cross-links in nucleosome core particles and cells.monofunctional alkylating agents preferentially react at the n7 position of 2'-deoxyguanosine in duplex dna. methylated dna, such as that produced by methyl methanesulfonate (mms) and temozolomide, exists for days in organisms. the predominant consequence of n7-methyl-2'-deoxyguanosine (mdg) is widely believed to be abasic site (ap) formation via hydrolysis, a process that is slow in free dna. examination of mdg reactivity within nucleosome core particles (ncps) provided two general observations ...201830429328
breast cancer: an examination of the potential of ackr3 to modify the response of cxcr4 to cxcl12.upon binding with the chemokine cxcl12, the chemokine receptor cxcr4 has been shown to promote breast cancer progression. this process, however, can be affected by the expression of the atypical chemokine receptor ackr3. given ackr3's ability to form heterodimers with cxcr4, we investigated how dual expression of both receptors differed from their lone expression in terms of their signalling pathways. we created single and double cxcr4 and/or ackr3 chinese hamster ovary (cho) cell transfectants. ...201830441765
γh2ax prefers late replicating metaphase chromosome regions.dna damage response (ddr) constitutes a protein pathway to handle eukaryotic dna lesions in the context of chromatin. ddr engages the recruitment of signaling, transducer, effector, chromatin modifiers and remodeling proteins, allowing cell cycle delay, dna repair or induction of senescence or apoptosis. an early ddr-event includes the epigenetic phosphorylation of the histone variant h2ax on serine 139 of the c-termini, so-called gammah2ax. gammah2ax foci detected by immunolabeling on interphas ...201830442336
cytotoxic and membrane cholesterol effects of ultraviolet irradiation and zinc oxide nanoparticles on chinese hamster ovary cells.zinc oxide (zno) nanoparticles are suspected to produce toxic effects toward mammalian cells; however, discrepancies in the extent of this effect have been reported between different cell lines. simultaneously, high levels of ultraviolet (uv-c) radiation can have carcinogenic effects. the mechanism of this effect is also not well understood. due to similarities in phenotype morphology after cell exposure to zno nanoparticles and uv-c irradiation, we emit the hypothesis that the toxicity of both ...201830445712
improving recombinant bone morphogenetic protein-4 (bmp-4) production by autoregulatory feedback loop removal using bmp receptor-knockout cho cell lines.a chinese hamster ovary (cho) cell line producing recombinant human bone morphogenetic protein-4 (rhbmp-4) (cho-bmp-4), which expresses essential components of bmp signal transduction, underwent autocrine bmp-4 signaling. rna seq analysis on cho host cells (dg44) treated with rhbmp-4 (20 µg/ml) suggested that rhbmp-4 induced signaling in cho cells could be a critical factor in limiting rhbmp-4 production and should be removed to improve rhbmp-4 production in recombinant cho (rcho) cells. the inh ...201930447330
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
characterizing and enhancing virus removal by protein a chromatography.protein a chromatography is an effective capture step to separate fc-containing biopharmaceuticals from cell culture impurities but is generally not effective for virus removal, which tends to vary among different products. previous findings have pointed to the differences in feedstocks to protein a, composed of the products and other cell culture-related impurities. to separate the effect of the feedstock components on virus removal, and understand why certain monoclonal antibody (mab) products ...201930450554
two human mars effectively increase transgene expression in transfected cho cells.matrix attachment regions (mars) can enhance the expression level of transgene in chinese hamster ovaries (cho) cell expression system. however, improvements in function and analyses of the mechanism remains unclear. in this study, we screened two new and more functional mar elements from the human genome dna. the human mar-3 and mar-7 element were cloned and inserted downstream of the polya site in a eukaryotic vector. the constructs were transfected into cho cells, and screened under g418 to p ...201930450759
fusion of factor ix to factor xiii-b sub-unit improves the pharmacokinetic profile of factor ix.prophylaxis is currently considered the optimal care for severe haemophilia. for patients and their families one of the major difficulties with prophylaxis is the need for frequent venipunctures. the half-life of standard factor ix (fix) concentrates is approximately 18 hours, which requires 2 or 3 intravenous infusions per week to achieve bleeding prevention in patients with severe haemophilia b. prolonging the half-life of fix can therefore reduce the frequency of infusions. recently, extended ...201830453348
comprehensive glycoproteomic analysis of chinese hamster ovary cells.the chinese hamster ovary (cho) cell line is a major expression system for the production of therapeutic proteins, the majority of which are glycoproteins, such as antibodies and erythropoietin (epo). the characterization glycosylation profile of therapeutic proteins produced from engineered cho cells and therapeutic functions, as well as side effects, are critical to understand the important roles of glycosylation. in this study, a large scale glycoproteomic workflow was established and applied ...201830457839
study of the cytotoxic and genotoxic potential of the carbonyl ruthenium(ii) compound, ct-[rucl(co)(dppb)(bipy)]pf6 [dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2'-bipyridine], by in vitro and in vivo assays.considering the promising previous results of ct-[rucl(co)(dppb)(bipy)]pf6 (where dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2'-bipyridine) as an antitumor agent, novel biological assays evaluating its toxicogenic potential were performed. the genotoxicity of the compound was evaluated by the in vitro micronucleus test (v79, chinese hamster lung fibroblasts; hepg2, hepatocellular carcinoma cells), in vivo bone marrow micronucleus test and comet assay in hepatocytes (swiss mice). the an ...201930460706
a comparative study of the bispecific monoclonal antibody, blinatumomab expression in cho cells and e. coli.the "bispecifics" market improved over the past decade due to the development of many technological platforms including bispecific t cell engagers (bites). the approval of blinatumomab, the most advanced bispecific t-cell engager (bite) in clinical trials, can be a significant milestone in the development of bispecific antibodies. both chinese hamster ovary (cho) cells and e. coli strain are considered as the most widely used hosts for the large-scale production of therapeutic monoclonal antibod ...201830461361
early porcine sapovirus infection disrupts tight junctions and uses occludin as a coreceptor.the genus sapovirus belongs to the family caliciviridae, and its members are common causative agents of severe acute gastroenteritis in both humans and animals. some caliciviruses are known to use either terminal sialic acids or histo-blood group antigens as attachment factors and/or cell surface proteins, such as cd300lf, cd300ld, and junctional adhesion molecule 1 of tight junctions (tjs), as receptors. however, the roles of tjs and their proteins in sapovirus entry have not been examined. in ...201930463963
na+ /ca2+ exchanger 1 is a key mechanosensitive molecule of the esophageal myenteric neurons.our earlier studies showed that mechanical stretch activates inhibitory motor neurons of the oesophagus; however, the underlying molecular mechanisms are unclear. here, we sought to examine if na+ /ca2+ exchanger 1 (ncx1) is responsible for the mechanosensitivity in the esophageal myenteric neurons (emn) of rats and humans.201930466198
exposure to the fungicide captan induces dna base alterations and replicative stress in mammalian cells.the classification of the fungicide captan (cas number: 133-06-2) as a carcinogen agent is presently under discussion. despite the mutagenic effect detected by the ames test and carcinogenic properties observed in mice, the genotoxicity of this pesticide in humans is still unclear. new information is needed about its mechanism of action in mammalian cells. here, we show that chinese hamster ovary (cho) cells exposed to captan accumulate fpg-sensitive dna base alterations. in cho and hela cells, ...201930471166
tracking lysosome migration within chinese hamster ovary (cho) cells following exposure to nanosecond pulsed electric fields.above a threshold electric field strength, 600 ns-duration pulsed electric field (nspef) exposure substantially porates and permeabilizes cellular plasma membranes in aqueous solution to many small ions. repetitive exposures increase permeabilization to calcium ions (ca2+) in a dosage-dependent manner. such exposure conditions can create relatively long-lived pores that reseal after passive lateral diffusion of lipids should have closed the pores. one explanation for eventual pore resealing is a ...201830477132
recombinant antibody production in cho and ns0 cells: differences and similarities.the commercial production of monoclonal antibodies (mabs) has revolutionized the treatment of many diseases, including cancer, multiple sclerosis, and rheumatoid arthritis. these biotherapeutics have the potential to generate a global annual revenue of more than us$150 billion. two cell hosts are predominantly utilized to produce these mabs: chinese hamster ovary (cho) cells and murine myeloma cells (ns0). by 2017, nearly one-quarter of all approved mabs in the market were produced using the ns0 ...201830499081
azure b affects amyloid precursor protein metabolism in ps70 cells.alzheimer's disease (ad), the most common form of dementia, is characterized by abundant deposition of amyloid-β (aβ) peptide that is the result of sequential cleavage of amyloid precursor protein (app) by β-secretase and γ-secretase. several studies have documented that inhibition of aβ peptide synthesis or facilitating its degradation is one of the attractive therapeutic strategies in ad. methylene blue (methb), which has recently been investigated in phase ii clinical trials, is a prominent i ...201930500345
production of a recombinant monoclonal antibody to herpes simplex virus glycoprotein d for immunoaffinity purification of tagged proteins.we have developed a stable chinese hamster ovary (cho) cell line for the production of a recombinant monoclonal antibody (mab) to a short protein sequence derived from the n-terminus of human herpes simplex virus type 1 glycoprotein d (hsv-1 gd). the antibody (designated r34.1) provides a useful tool for the immunoaffinity purification of hsv-1 gd tagged proteins, and provides a generic purification system by which various proteins and peptides can be purified. recombinant 34.1 was assembled usi ...201930502324
[site-specific o-glycosylation analysis of therapeutic fc-fusion protein by mass spectrometry].therapeutic fc-fusion proteins, created by linking bioactive peptides or receptor proteins to the fc moiety of igg, are currently being developed. in this development process, a gly-gly-gly-ser linker (g4s linker) is often used to link the peptide/protein and the fc portion. o-xylose-type core glycans of glycosaminoglycan are known to attach to the ser residue on the gsg motif in the g4s linker peptide repeats of the fc fusion protein produced using the chinese hamster ovary (cho) cell expressio ...201830504662
epigenetic regulation of gene expression in chinese hamster ovary cells in response to the changing environment of a batch culture.the existence of dynamic cellular phenotypes in changing environmental conditions is of major interest for cell biologists who aim to understand the mechanism and sequence of regulation of gene expression. in the context of therapeutic protein production by chinese hamster ovary (cho) cells, a detailed temporal understanding of cell-line behavior and control is necessary to achieve a more predictable and reliable process performance. of particular interest are data on dynamic, temporally resolve ...201930512195
glyco-engineered cho cell lines producing alpha-1-antitrypsin and c1 esterase inhibitor with fully humanized n-glycosylation profiles.recombinant chinese hamster ovary (cho) cells are able to provide biopharmaceuticals that are essentially free of human viruses and have n-glycosylation profiles similar, but not identical, to humans. due to differences in n-glycan moieties, two members of the serpin superfamily, alpha-1-antitrypsin (a1at) and plasma protease c1 inhibitor (c1inh), are currently derived from human plasma for treating a1at and c1inh deficiency. deriving therapeutic proteins from human plasma is generally a cost-in ...201930513349
growth behavior of human adipose tissue-derived stromal/stem cells at small scale: numerical and experimental investigations.human adipose tissue-derived stromal/stem cells (hascs) are a valuable source of cells for clinical applications, especially in the field of regenerative medicine. therefore, it comes as no surprise that the interest in hascs has greatly increased over the last decade. however, in order to use hascs in clinically relevant numbers, in vitro expansion is required. single-use stirred bioreactors in combination with microcarriers (mcs) have shown themselves to be suitable systems for this task. howe ...201830518117
the mouse-canine chimeric anti-dog podoplanin antibody p38b exerts antitumor activity in mouse xenograft models.podoplanin (pdpn) is a type i transmembrane heavily glycosylated sialoglycoprotein that is expressed in normal tissues such as pulmonary type i alveolar cells, renal podocytes, and lymphatic endothelial cells. pdpn overexpression in cancerous tissue is associated with hematogenous metastasis through interactions with the c-type lectin-like receptor 2 (clec-2). previously, we have reported the development of a mouse monoclonal antibody (mab), pmab-38 (igg1, kappa) against dog pdpn (dpdpn). pmab-3 ...201930519645
multistage antiplasmodium activity of astemizole analogues and inhibition of hemozoin formation as a contributor to their mode of action.a drug repositioning approach was leveraged to derivatize astemizole (ast), an antihistamine drug whose antimalarial activity was previously identified in a high-throughput screen. the multistage activity potential against the plasmodium parasite's life cycle of the subsequent analogues was examined by evaluating against the parasite asexual blood, liver, and sexual gametocytic stages. in addition, the previously reported contribution of heme detoxification to the compound's mode of action was i ...201930525439
evaluation of pta-derived ruthenium(ii) and iridium(iii) quinoline complexes against chloroquine-sensitive and resistant strains of the plasmodium falciparum malaria parasite.cationic 1,3,5‑triaza‑phosphaadamantane (pta) quinoline ruthenium(ii) and iridium(iii) complexes were successfully synthesized and characterized using standard spectroscopic and analytical techniques. the complexes were evaluated for their in vitro antiplasmodial activities against the chloroquine-sensitive (cqs) nf54 and chloroquine-resistant (cqr) k1 strains of the plasmodium falciparum species of the malaria parasite and were found to exhibit good activities in the sensitive strain but modera ...201930529881
amber suppression coupled with inducible surface display identifies cells with high recombinant protein productivity.cell line development (cld) for biotherapeutics is a time- and resource-intensive process requiring the isolation and screening of large numbers of clones to identify high producers. novel methods aimed at enhancing cell line screening efficiency using markers predictive of productivity early in the cld process are needed to reliably generate high-yielding cell lines. to enable efficient and selective isolation of antibody expressing chinese hamster ovary cells by fluorescence-activated cell sor ...201930536645
a novel muc1 aptamer-modified plga-epirubicin-pβae-antimir-21 nanocomplex platform for targeted co-delivery of anticancer agents in vitro and in vivo.conventional chemotherapy suffers from several drawbacks, including toxic side effects together with the development of resistance to the chemical agents. therefore, exploring alternative therapeutic approaches as well as developing targeted delivery systems are in demand. oligonucleotide-based therapy has emerged as a promising and alternative procedure for treating malignancies involving gene-related diseases. in the current study, a targeted delivery system was designed to target cancer cells ...201930537619
lack of mutagenicity, genotoxicity and developmental toxicity in safety assessment tests of lactobacillus mali aps1.lactobacillus (l.) mali aps1 isolated from sugary kefir grains has been proven to affect energy and glucose homeostasis. however, without proper safety assessment it cannot be recommended as probiotics for human consumption. for genotoxicity, the ames test showed no mutagenic effect of l. mali aps1 in the presence or absence of s9 mix metabolic activation. in-vitro mammalian chromosomal aberration test showed that the number of chinese hamster ovary cells with abnormal chromosomes was <5% after ...201830543670
efficient interleukin-21 production by optimization of codon and signal peptide in chinese hamster ovarian cells.interleukin-21 is a common γ-chain cytokine that controls the immune responses of b cells, t cells, and natural killer cells. targeting il-21 to strengthen the immune system is promising for the development of vaccines as well as anti-infection and anti-tumor therapies. however, the practical application of il-21 is limited by the high production cost. in this study, we improved il-21 production by codon optimization and selection of appropriate signal peptide in cho-k1 cells. codon-optimized or ...201930544288
quantitative model for ion transport and cytoplasm conductivity of chinese hamster ovary cells.in mammalian cells cytoplasm ion concentrations and hence cytoplasm conductivity is an important indicator of their physiological state. changes in the cytoplasm conductivity has been associated with physiological changes such as progression of cancer and apoptosis. in this work, a model that predicts the effects of physiological changes in ion transport on the cytoplasm conductivity of chinese hamster ovary (cho) cells is demonstrated. we determined cho-specific model parameters, na+/k+ atpase ...201830546044
impact of cell culture media additives on igg glycosylation produced in chinese hamster ovary cells.glycosylation is a key critical quality attribute for monoclonal antibodies and other recombinant proteins because of its impact on effector mechanisms and half-life. in this study, a variety of compounds were evaluated for their ability to modulate glycosylation profiles of recombinant monoclonal antibodies produced in chinese hamster ovary cells. compounds were supplemented into the cell culture feed of fed-batch experiments performed with a cho k1 and a cho dg44 cell line expressing a recombi ...201930552760
the effect of hyperosmolality application time on production, quality, and biopotency of monoclonal antibodies produced in cho cell fed-batch and perfusion cultures.hyperosmolality has been commonly investigated due to its effects on the production and quality characteristics of monoclonal antibodies (mabs) produced in cho cell fed-batch cultures. however, the application of hyperosmolality at different times and its effect on biopotency have seldom been researched, especially in perfusion culture. in our study, different degrees of hyperosmolality induced by sodium chloride were investigated in anti-ige rcho cell fed-batch cultures and anti-cd52 rcho cell ...201930554388
muscarinic agonist, (±)-quinuclidin-3-yl-(4-fluorophenethyl)(phenyl)carbamate: high affinity, but low subtype selectivity for human m1 - m5 muscarinic acetylcholine receptors.novel quinuclidinyl n-phenylcarbamate analogs were synthesized, and binding affinities at m1-m5 muscarinic acetylcholine receptor (machr) subtypes were determined using chinese hamster ovary (cho) cell membranes stably expressing one specific subtype of human machr. although not subtype selective, the lead analog (±)-quinuclidin-3-yl-(4-fluorophenethyl)(phenyl)carbamate (3c) exhibited the highest affinity (ki = 2.0, 13, 2.6, 2.2, 1.8 nm) at each of the m1-m5 machrs, respectively. based on result ...201930554957
multiple modes of action of hydrophobic amines and their guanidine analogues on asic1a.hydrophobic monoamines containing only a hydrophobic/aromatic moiety and protonated amino group are a recently described class of acid-sensing ion channel (asic) modulators. intensive studies have revealed a number of active compounds including endogenous amines and pharmacological agents and shown that these compounds potentiate and inhibit asics depending on their specific structure and on subunit composition of the target channel. the action of monoamines also depends on the application proto ...201930557561
differential regulation of thermodynamic binding forces of levocetirizine and (s)-cetirizine by lys191 in human histamine h₁ receptors.cetirizine is a zwitterionic second-generation antihistamine containing r- and s-enantiomers, levocetirizine, and (s)-cetirizine. levocetirizine is known to have a higher affinity for the histamine h₁ receptors than (s)-cetirizine; ligand-receptor docking simulations have suggested the importance of the formation of a salt bridge (electrostatic interaction) between the carboxylic group of levocetirizine and the lys191 residue at the fifth transmembrane domain of human histamine h₁ receptors. in ...201830558340
structural and epitope analysis (t- and b-cell epitopes) of hepatitis c virus (hcv) glycoproteins: an in silico approach.chronic infection with hepatitis c virus (hcv) poses a major risk for liver disease like cirrhosis, liver failure and hepatocellular carcinoma. in terms of percentage, the prevalence of hcv in india was found to be low to moderate (1-1.5%), but in terms of sheer numbers, india has a significant number of global hcv patients. presently, hcv can be treated with direct acting-antibody drugs but there is no prophylactic or therapeutic vaccine available against it. in hcv infection, t- and b-cell imm ...201830568344
tak-442, a direct factor xa inhibitor, inhibits monocyte chemoattractant protein 1 production in endothelial cells via involvement of protease-activated receptor 1.oral blood coagulation inhibitors and their receptors, such as factor xa (fxa), thrombin, and the thrombin receptor protease-activated receptor 1 (par1), are entered into clinical trials for acute coronary syndrome therapy; however, the results obtained so far are different for each drug. the underlying mechanisms of the results have not been fully investigated. we studied the in vitro anti-inflammatory effects of the selective fxa inhibitor tak-442 on human endothelial cells, with comparing tho ...201830568593
secretory leakage of igg1 aggregates from recombinant chinese hamster ovary cells.aggregation of therapeutic antibodies is one of the most important issues to be resolved in manufacturing processes because of reduced efficacy and immunogenicity. despite aggregation studies in vitro, little is known about the aggregation mechanism in cell culture processes. in this study, we investigated the process of aggregate formation of igg1 antibodies during the culture of chinese hamster ovary (cho) cells to determine how aggregation occurs. a recombinant cho cell line was cultivated in ...201930580968
utilizing a regulated targeted integration cell line development approach to systematically investigate what makes an antibody difficult to express.chinese hamster ovary (cho) cells are conventionally used to generate therapeutic cell lines via random integration (ri), where desired transgenes are stably integrated into the genome. targeted integration (ti) approaches, which involve integration of a transgene into a specific locus in the genome, are increasingly utilized for cho cell line development (cld) in recent years. none of these cld approaches, however, are suitable for expression of toxic or difficult-to-express molecules, or for d ...201930592567
cxcl10 production in equine monocytes is stimulated by interferon-gamma.c-x-c motif ligand 10 (cxcl10) is a pro-inflammatory chemokine and has been extensively evaluated in people and mice. in horses, cxcl10 and its involvement in host immunity has rarely been analyzed due to the lack of specific antibodies. we generated a mab specific for the equine chemokine cxcl10 using hybridoma technology. antibody specificity was confirmed by intracellular staining and flow cytometric analysis of chinese hamster ovary (cho) cells expressing equine rcxcl10, while cho cells expr ...201930593347
c-c motif chemokine ligand (ccl) production in equine peripheral blood mononuclear cells identified by newly generated monoclonal antibodies.chemokines are soluble molecules directing immune cell trafficking and homing, mediating inflammation, and initiating immune responses to infection. in horses, the analysis of chemokines has been limited by the lack of specific antibodies. we generated mabs specific for the equine c-c motif chemokine ligands (ccl) ccl2 (mcp-1), ccl3 (mip-1α), ccl5 (rantes) and ccl11 (eotaxin) using hybridoma technology. antibody specificity was confirmed by intracellular staining of chinese hamster ovary cells t ...201830596378
interaction of cell culture process parameters for modulating mab afucosylation.the extent of afucosylation, which refers to the absence of core fucose on fc glycans, can correlate positively with the antibody-dependent cellular cytotoxicity (adcc) activity of a monoclonal antibody (mab). therefore, it is important to maintain consistent afucosylation during cell culture process scale-up in bioreactors for a mab with adcc activity. however, there is currently a lack of understanding about the impact of partial pressure of carbon dioxide (pco2 )-a parameter that can vary wit ...201930597531
fmoc-ff and hexapeptide-based multicomponent hydrogels as scaffold materials.short peptides or single amino acids are interesting building blocks for fabrication of hydrogels, frequently used as extracellular matrix-mimicking scaffolds for cell growth in tissue engineering. the combination of two or more peptide hydrogelators could allow obtaining different materials exhibiting new architectures, tunable mechanical properties, high stability and improved biofunctionality. here we report on the synthesis, formulation and multi-scale characterization of peptide-based mixed ...201930601569
a pathogenic tau fragment compromises microtubules, disrupts insulin signaling and induces the unfolded protein response.human tauopathies including alzheimer's disease, progressive supranuclear palsy and related disorders, are characterized by deposition of pathological forms of tau, synaptic dysfunction and neuronal loss. we have previously identified a pathogenic c-terminal tau fragment (tau35) that is associated with human tauopathy. however, it is not known how tau fragmentation affects critical molecular processes in cells and contributes to impaired physiological function. chinese hamster ovary (cho) cells ...201930606258
comparison of integrases identifies bxb1-ga mutant as the most efficient site-specific integrase system in mammalian cells.phage-derived integrases can catalyze irreversible, site-specific integration of transgenic payloads into a chromosomal locus, resulting in mammalian cells that stably express transgenes or circuits of interest. previous studies have demonstrated high-efficiency integration by the bxb1 integrase in mammalian cells. here, we show that a point mutation (bxb1-ga) in bxb1 target sites significantly increases bxb1-mediated integration efficiency at the rosa26 locus in chinese hamster ovary cells, res ...201930609349
analysis of the immunoglobulin g (igg) secretion efficiency in recombinant chinese hamster ovary (cho) cells by using citrine-fusion igg.biopharmaceuticals represented by immunoglobulin g (igg) are produced by the cultivation of recombinant animal cells, especially chinese hamster ovary (cho) cells. it is thought that the intracellular secretion process of igg is a bottleneck in the production of biopharmaceuticals. many studies on the regulation of endogenous secretory protein expression levels have shown improved productivity. however, these strategies have not universally improved the productivity of various proteins. a more r ...201930610509
kcnq1 rescues tmc1 plasma membrane expression but not mechanosensitive channel activity.transmembrane channel-like protein isoform 1 (tmc1) is essential for the generation of mechano-electrical transducer currents in hair cells of the inner ear. tmc1 disruption causes hair cell degeneration and deafness in mice and humans. although thought to be expressed at the cell surface in vivo, tmc1 remains in the endoplasmic reticulum when heterologously expressed in standard cell lines, precluding determination of its roles in mechanosensing and pore formation. here, we report that the kcnq ...201930613966
anti-hyperglycemic and genotoxic studies of 1-o-methyl chrysophanol, a new anthraquinone isolated from amycolatopsis thermoflava strain sfma-103.the compound 1-o-methyl chrysophanol (omc) which belongs to a class of hydroxyanthraquinones was isolated from amycolatopsis thermoflava strain sfma-103 and studied for their anti-diabetic properties. omc was evaluated as an anti-diabetic agent based on in silico studies which initially predicted the binding energy with α-amylase (-188.81 kj mol-1) and with α-glucosidase (70.53 kj mol-1). further, these results were validated based on enzyme inhibition assays where omc demonstrated enzyme inhibi ...201930614298
expression in eukaryotic cells and purification of synthetic gene encoding enterocin p: a bacteriocin with broad antimicrobial spectrum.due to the emergence of multidrug-resistant bacteria, treatment options for infectious diseases are decreasing. bacteriocins are small antimicrobial peptides produced by numerous bacteria that offer alternative therapeutic strategies to combat multidrug-resistant bacterial infections. we evaluated the cloning, functional expression, and antimicrobial activities of enterocin p (entp), a class ii bacteriocin member, in chinese hamster ovary (cho) cells. a synthetic gene matching cho cell codon usa ...201930617751
zinc oxide nanoparticles induced gene mutation at the hgprt locus and cell cycle arrest associated with apoptosis in v-79 cells.in recent years, the large-scale production of zno nanoparticles (nps) for various applications is increasing exponentially and may pose serious health issues when inhaled either during occupational exposure or in consumer settings. the mechanisms underlying the toxicity of nps have recently been studied intensively. despite the existing studies, the mutagenicity of zno nps in the eukaryotic system is still unclear. therefore, the aim of the present study was to investigate the mutagenic potenti ...201930618096
optimization of sequence, display, and mode of operation of igg-binding peptide ligands to develop robust, high-capacity affinity adsorbents that afford high igg product quality.this work presents the use of peptide ligand hwrgwv and its cognate sequences to develop affinity adsorbents that compete with protein a in terms of binding capacity and quality of the eluted product. first, the peptide ligand was conjugated to crosslinked agarose resins (workbeads) at different densities and using different spacer arms. the optimization of ligand density and display resulted in values of static and dynamic binding capacity of 85 mg/ml and 65 mg/ml, respectively. a selected pept ...201930621158
analysis of golgi ph in chinese hamster ovary cells using ratiometric ph-sensitive fluorescent proteins.acidic golgi ph plays an important role in protein glycosylation, one of the critical quality attributes of therapeutic proteins. to determine the intracellular golgi ph during culture, stable chinese hamster ovary (cho) cell clones expressing phluorin2, a ratiometric ph-sensitive fluorescent protein (fp), in the cis- and trans-golgi, were constructed by fusing phluorin2 with specific targeting proteins, acetylglucosaminyltransferase, and a galactosyltransferase, respectively. stable cho cell cl ...201930636290
secretion analysis of intracellular "difficult-to-express" immunoglobulin g (igg) in chinese hamster ovary (cho) cells.the chinese hamster ovary (cho) cell line is the most widely used host cell for therapeutic antibody production. although its productivity has been improved by various strategies to satisfy the growing global demand, some difficult-to-express (dte) antibodies remain at low secretion levels. to improve the production of various therapeutic antibodies, it is necessary to determine possible rate-limiting steps in dte antibody secretion in comparison with other high igg producers. here, we analyzed ...201930637508
increased growth rate and productivity following stable depletion of mir-7 in a mab producing cho cell line causes an increase in proteins associated with the akt pathway and ribosome biogenesis.cell line engineering using micrornas represents a desirable route for improving the efficiency of recombinant protein production by cho cells. in this study we generated stable cho dp12 cells expressing a mir-7 sponge transcript which sequesters mir-7 from its endogenous targets. depletion of mir-7 results in a 65% increase in cell growth and >3-fold increase in yield of secreted igg protein. quantitative labelfree lc-ms/ms proteomic profiling was carried out to identify the targets of mir-7 an ...201930641232
silkworm storage protein 1 inhibits autophagy-mediated apoptosis.autophagy is a natural physiological process, and it induces the lysosomal degradation of intracellular components in response to environmental stresses, including nutrient starvation. although an adequate autophagy level helps in cell survival, excessive autophagy triggered by stress such as starvation leads to autophagy-mediated apoptosis. chinese hamster ovary (cho) cells are widely used for producing biopharmaceuticals, including monoclonal antibodies. however, apoptosis induced by high stre ...201930646576
effect of adenovirus infection on transgene expression under the adenoviral mlp/tpl and the cmvie promoter/enhancer in cho cells.the adenovirus major late promoter (mlp) and its translational regulator - the tripartite leader (tpl) sequence - can actively drive efficient gene expression during adenoviral infection. however, both elements have not been widely tested in transgene expression outside of the adenovirus genome context. in this study, we tested whether the combination of mlp and tpl would enhance transgene expression beyond that of the most widely used promoter in transgene expression in mammalian cells, the cyt ...201730647657
a novel methodology to assess linear energy transfer and relative biological effectiveness in proton therapy using pairs of differently doped thermoluminescent detectors.a new methodology for assessing linear energy transfer (let) and relative biological effectiveness (rbe) in proton therapy beams using thermoluminescent detectors is presented. the method is based on the different let response of two different lithium fluoride thermoluminescent detectors (lif:mg,ti and lif:mg,cu,p) for measuring charged particles. the relative efficiency of the two detector types was predicted using the recently developed microdosimetric d(z) model in combination with the monte ...201930650402
use of a branched linker for enhanced biosensing properties in igg detection from mixed chinese hamster ovary cell cultures.tris(2-aminoethyl)-amine (tren), a branched amine, was coupled to planar surfaces of alkanethiol self-assembled monolayers (sams) to increase the grafting density of igg-binding peptide (hwrgwv or hwrgwvg) on gold surfaces. one of the three primary amine pendant groups of tren anchors onto the sam, while the other two are available for grafting with the c-termini of the peptide. the ellipsometric peptide density on the sam-branched amine was 1.24 molecules nm-2. the surfaces carrying the peptide ...201930653289
incorporation of cd40 ligand or granulocyte-macrophage colony stimulating factor into hantaan virus (htnv) virus-like particles significantly enhances the long-term immunity potency against htnv infection.hantavirus infections cause severe haemorrhagic fever with renal syndrome (hfrs) in humans and are associated with high fatality rates. in 2017, numerous outbreaks were reported in china and germany. this represents a significant public-healthcare issue with no effective hfrs vaccines that offer a long-term immune response. in this study, we investigated the long-term humoral and cellular immune responses and protective immunity of hantaan virus (htnv) granulocyte-macrophage colony stimulating f ...201930657443
bmn 250, a fusion of lysosomal alpha-n-acetylglucosaminidase with igf2, exhibits different patterns of cellular uptake into critical cell types of sanfilippo syndrome b disease pathogenesis.sanfilippo syndrome type b (sanfilippo b; mucopolysaccharidosis type iiib) occurs due to genetic deficiency of lysosomal alpha-n-acetylglucosaminidase (naglu) and subsequent lysosomal accumulation of heparan sulfate (hs), which coincides with devastating neurodegenerative disease. because naglu expressed in chinese hamster ovary cells is not mannose-6-phosphorylated, we developed an insulin-like growth factor 2 (igf2)-tagged naglu molecule (bmn 250; tralesinidase alfa) that binds avidly to the i ...201930657762
generation of site-distinct n-glycan variants for in vitro bioactivity testing.glycosylation, a critical product quality attribute, may affect the efficacy and safety of therapeutic proteins in vivo. chinese hamster ovary fed-batch cell culture batches yielded consistent glycoprofiles of a fc-fusion antibody comprizing three different n-glycosylation sites. by adding media supplements at specific concentrations in cell culture and applying enzymatic glycoengineering, a diverse n-glycan variant population was generated, including high mannose, afucosylated, fucosylated, aga ...201930659587
chromophore pre-maturation for improved speed and sensitivity of split-gfp monitoring of protein secretion.complementation-dependent fluorescence is a powerful way to study co-localization or interactions between biomolecules. a split-gfp variant, involving the self-associating gfp 1-10 and gfp 11, has previously provided a convenient approach to measure recombinant protein titers in cell supernatants. a limitation of this approach is the slow chromophore formation after complementation. here, we alleviate this lag in signal generation by allowing the gfp 1-10 chromophore to mature on a solid support ...201930670736
histidine-rich cell-penetrating peptide for cancer drug delivery and its uptake mechanism.in this work, we report a drug delivery system based on the ph-responsive self-assembly and -disassembly behaviors of peptides. here, a systematically designed histidine-rich lipidated peptide (np1) is presented to encapsulate and deliver an anticancer drug ellipticine (ept) into two model cells: non-small-cell lung carcinoma and chinese hamster ovary cells. the mechanism of ph-responsive peptide self-assembly and -disassembly involved in the drug encapsulation and release process are extensivel ...201930673275
multiple mechanisms underlie increased cardiac late sodium current.we recently reported a quantitative relationship between the degree of functional perturbation reported in the literature for 356 variants in the cardiac sodium channel gene scn5a and the penetrance of resulting arrhythmia phenotypes. in the course of that work, we identified multiple scn5a variants, including r1193q, that are common in populations but are reported in human embryonic kidney (hek) cells to generate large late sodium current (ina-l).201930677491
pmab-210: a monoclonal antibody against pig podoplanin.podoplanin (pdpn) is a type i transmembrane glycoprotein that is expressed in normal tissues, including renal corpuscles and type i lung alveolar cells. monoclonal antibodies (mabs) against human, mouse, rat, rabbit, dog, cat, and bovine pdpns have already been established; however, antipig pdpn (ppdpn) mabs have not. we therefore immunized mice with ppdpn-overexpressing chinese hamster ovary (cho)-k1 cells (cho/ppdpn), and screened hybridomas, which are producing anti-ppdpn mabs. one of mabs, p ...201930681406
dissecting n-glycosylation dynamics in chinese hamster ovary cells fed-batch cultures using time course omics analyses.n-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies. a robust control strategy is needed to dial in appropriate glycosylation profile during the course of cell culture processes accurately. however, n-glycosylation dynamics remains insufficiently understood owing to the lack of integrative analyses of factors that influence the dynamics, including sugar nucleotide donors, glycosyltransfe ...201930682623
current state-of-the-art in plant-based antibody production systems.monoclonal antibodies represent the major class of biopharmaceutical products (for therapeutics and diagnostics) with an increasing demand that reaches several tons per year worldwide. traditional large-scale manufacturing processes are based on stirred tank bioreactors for the growth of chinese hamster ovary cells (cho) which requires high initial investments and production costs. therefore, there is an urgent need for alternative production platforms that can at least act as a complement to th ...201930684155
intact bioactivities and improved pharmacokinetic of the sl335-ifn-β-1a fusion protein that created by genetic fusion of sl335, a human anti-serum albumin fab, and human interferon-β.recombinant human interferon beta (rifn-β) has long been used as a first-line treatment for multiple sclerosis (ms), and any attempt to develop a long-acting rifn-β is desirable since only one pegylated version of long-acting rifn-β-1a (plegridy) is currently available in clinics. previously, we reported that sl335, a human fab molecule specific to serum albumin, exhibits an extended serum half-life via utilizing the fcrn recycling mechanism. with the ultimate goal of developing a long-acting ri ...201930684504
silk sericin hydrolysate is a potential candidate as a serum-substitute in the culture of chinese hamster ovary and henrietta lacks cells.the silk sericin hydrolysate (ssh) from the waste of silk processing as a substitute of fetal bovine serum (fbs) was used for the culture of chinese hamster ovary (cho) cells and henrietta lacks (hela) strain of human cervical cancer cells. the survival ratio of these cells cultured in ssh media were similar to or higher than those in fbs media. especially after the serum was replaced by low concentration of ssh at 15.0 μg/ml for 5 d, the proliferation of both cells was also similar to or higher ...201930690536
an oral toxicity test in rats and a genotoxicity study of extracts from the stems of opuntia ficus-indica var. saboten.opuntia ficus-indica var. saboten (ofis) is used widely in korea to treat constipation due to its diuretic effects and its enhancement of bowel function and appetite. however, its safety has not yet been established. the aim of this study was to evaluate the repeated oral toxicity and genotoxicity of ofis extract (oe).201930691445
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