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sv40 intron, a potent strong intron element that effectively increases transgene expression in transfected chinese hamster ovary cells.chinese hamster ovary (cho) cells have become the most widely utilized mammalian cell line for the production of recombinant proteins. however, the product yield and transgene instability need to be further increased and solved. in this study, we investigated the effect of five different introns on transgene expression in cho cells. hcmv intron a, adenovirus tripartite leader sequence intron, sv40 intron, chinese hamster ef-1alpha gene intron 1 and intervening sequence intron were cloned downstr ...201829441681
using a dihydrofolate reductase-based strategy for producing the biosimilar version of pertuzumab in cho-s cells.targeted therapy using monoclonal antibodies (mabs) against epidermal growth factor receptor-2 (erbb2) has been utilized for the treatment of breast cancer, recently. pertuzumab, one of the anti-erbb2 mabs, was approved by fda in 2012 for the treatment of metastatic breast cancer. the aim of this study was to produce biosimilar version of pertuzumab in chinese hamster ovary (cho)-s cell line, and compare its erbb2-binding and biological activities, with commercial drug, perjeta. to this end, a d ...201829437532
strategy for generating sequence-defined aptamer reagent sets for detecting protein contaminants in biotherapeutics.biologic drugs are typically manufactured in mammalian host cells, and it is critical from a drug safety and efficacy perspective to detect and remove host cell proteins (hcps) during production. this is currently achieved with sets of polyclonal antibodies (pabs), but these suffer from critical shortcomings because their composition is inherently undefined, and they cannot detect nonimmunogenic hcps. in this work, we report a high-throughput screening and array-based binding characterization st ...201829436820
butyrated mannac analog improves protein expression in chinese hamster ovary cells.the chemical additive sodium butyrate (nabu) has been applied in cell culture media as a direct and convenient method to increase the protein expression in chinese hamster ovary (cho) and other mammalian cells. in this study, we examined an alternative chemical additive, 1,3,4-o-bu3 mannac, for its effect on recombinant protein production in cho. supplementation with 1,3,4-o-bu3 mannac for two stable cho cell lines, expressing human erythropoietin or igg, enhanced protein expression for both pro ...201829427449
both the ph domain and n-terminal region of oxysterol-binding protein related protein 8s are required for localization to pm-er contact sites.oxysterol-binding protein-related proteins are implicated in the sensing and transporting lipids at the membrane contact sites. one of the members of the mammalian orp family, orp8, is thought to transport lipids through directly tethering both er and pm membranes. targeting to pm is thought to be mediated by n-terminal pleckstrin homology domain via binding to phosphoinositides. sequence alignments and nmr structural determination revealed that the ph domain of orp8 is atypical and contains an ...201829409900
rimonabant, a potent cb1 cannabinoid receptor antagonist, is a gαi/o protein inhibitor.rimonabant is a potent and selective cannabinoid cb1 receptor antagonist widely used in animal and clinical studies. besides its antagonistic properties, numerous studies have shown that, at micromolar concentrations rimonabant behaves as an inverse agonist at cb1 receptors. the mechanism underpinning this activity is unclear. here we show that micromolar concentrations of rimonabant inhibited gαi/o-type g proteins, resulting in a receptor-independent block of g protein signaling. accordingly, r ...201829407764
tumor targeting with novel pyridyl 6-substituted pyrrolo[2,3- d]pyrimidine antifolates via cellular uptake by folate receptor α and the proton-coupled folate transporter and inhibition of de novo purine nucleotide biosynthesis.tumor-targeted specificities of 6-substituted pyrrolo[2,3- d]pyrimidine analogues of 1, where the phenyl side-chain is replaced by 3',6' (5, 8), 2',5' (6, 9), and 2',6' (7, 10) pyridyls, were analyzed. proliferation inhibition of isogenic chinese hamster ovary (cho) cells expressing folate receptors (frs) α and β were in rank order, 6 > 9 > 5 > 7 > 8, with 10 showing no activity, and 6 > 9 > 5 > 8, with 10 and 7 being inactive, respectively. antiproliferative effects toward frα- and frβ-expressi ...201829425443
13 c flux analysis reveals that rebalancing medium amino acid composition can reduce ammonia production while preserving central carbon metabolism of cho cell cultures.13 c metabolic flux analysis (mfa) provides a rigorous approach to quantify intracellular metabolism of industrial cell lines. in this study, 13 c mfa was used to characterize the metabolic response of chinese hamster ovary (cho) cells to a novel medium variant designed to reduce ammonia production. ammonia inhibits growth and viability of cho cell cultures, alters glycosylation of recombinant proteins, and enhances product degradation. ammonia production was reduced by manipulating the amino ac ...201829405605
receptor-specific crosstalk between prostanoid e receptor 3 and bombesin receptor subtype 3.bombesin receptor subtype 3 (brs-3) is a gpcr that is expressed in the cns, peripheral tissues, and tumors. our understanding of brs-3's role in physiology and pathophysiology is limited because its natural ligand is unknown. in an attempt to identify this ligand, we screened toad skin ( bufo bufo gargarizans cantor) extracts and identified prostaglandins as putative ligands. in brs-3-transfected human embryonic kidney (hek) cells, we found that prostaglandins, with prostaglandin e2 (pge2) being ...201829401613
inhibitory effect of bofutsushosan (fang feng tong sheng san) on glucose transporter 5 function in vitro.bofutsushosan (bts; fang feng tong sheng san in chinese) is a formula in traditional japanese kampo medicine and chinese medicine comprising eighteen crude drugs, and is used to treat obesity and metabolic syndrome. fructose is contained in refreshing beverages as high-fructose corn syrup, and is associated with obesity. fructose is absorbed via glucose transporter 5 (glut5) in the intestine. therefore, the inhibition of glut5 is considered to be a target of obesity drugs. we evaluated the inhib ...201829423591
"antimicrobial and antiproliferative activity of essential oil, aqueous and ethanolic extracts of ocimum micranthum willd leaves".ocimum micranthum willd is a plant used in traditional medicine practiced in the region of the yucatan peninsula. in particular, it is used for the treatment of cutaneous infections and wound healing, however there are currently no existing scientific studies that support these applications. the aim of the present study was to evaluate the antimicrobial and the in vitro proliferative activity (on healthy mammalian cell lines) of the essential oil and extracts (aqueous and ethanolic) of this plan ...201829422064
[impact of neutron radiation on the viability of tumor cells cultured in the presence of boron-10 isotope].to investigate the impact of a neutron beam formed with the accelerator-based epithermal neutron source designed at the g.i. budker institute of nuclear physics (inp) on the viability of human and animal tumor cells cultured in the presence of boron-10 isotope.201830241133
site-specific integration ushers in a new era of precise cho cell line engineering.chinese hamster ovary (cho) cells are widely used for the production of therapeutic proteins. customarily, cho production cell lines are established through random integration, which requires laborious screening of many clones to isolate suitable producers. in contrast, site-specific integration (ssi) accelerates cell line development by targeting integration of transgenes to pre-validated genomic loci capable of supporting high and stable expression. to date, a relatively small number of these ...201831086757
bioinformatic analysis of chinese hamster ovary host cell protein lipases.complete, accurate genome assemblies are necessary to design targets for genetic engineering strategies. successful gene knockdowns and knockouts in chinese hamster ovary (cho) cells may prevent the expression of difficult-to-remove host cell proteins (hcps). hcps, if not removed, can cause problems in stability, safety, and efficacy of the biotherapeutic. a significantly improved chinese hamster (ch) reference genome was used to identify new knockout targets with similar predicted functions and ...201830911190
an lc-ms-based lipidomics pre-processing framework underpins rapid hypothesis generation towards cho systems biotechnology.given a raw lc-ms dataset, it is often required to rapidly generate initial hypotheses, in conjunction with other 'omics' datasets, without time-consuming lipid verifications. furthermore, for meta-analysis of many datasets, it may be impractical to conduct exhaustive confirmatory analyses. in other cases, samples for validation may be difficult to obtain, replicate or maintain. thus, it is critical that the computational identification of lipids is of appropriate accuracy, coverage, and unbiase ...201830830409
mitochondrial aconitase is a key regulator of energy production for growth and protein expression in chinese hamster ovary cells.mammalian cells like chinese hamster ovary (cho) cells are routinely used for production of recombinant therapeutic proteins. cells require a continuous supply of energy and nutrients to sustain high cell densities whilst expressing high titres of recombinant proteins. cultured mammalian cells are primarily dependent on glucose and glutamine metabolism for energy production.201830830403
a proteomic profiling dataset of recombinant chinese hamster ovary cells showing enhanced cellular growth following mir-378 depletion.the proteomic data presented in this article provide supporting information to the related research article "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" (costello et al., in press) [1]. control and microrna-378 depleted cho dp12 cells were profiled using label-free quantitative proteomic profiling. cho dp12 cells were collected on day 4 and 8 of batch culture, subcellular pr ...201830761351
tag-on-demand: exploiting amber codon suppression technology for the enrichment of high-expressing membrane protein cell lines.membrane proteins play key roles in the evolution of numerous diseases and as a result have become the most dominant class of targets for therapeutic intervention. however, their poor expression and detection oftentimes prohibit drug discovery and screening efforts. herein, we have developed an approach, named 'tag-on-demand' that exploits amber suppression to control the expression of 'tagged' membrane proteins for detection and selections, yet can be turned off for expression of the protein in ...201830753634
point-of-care production of therapeutic proteins of good-manufacturing-practice quality.manufacturing technologies for biologics rely on large, centralized, good-manufacturing-practice (gmp) production facilities and on a cumbersome product-distribution network. here, we report the development of an automated and portable medicines-on-demand device that enables consistent, small-scale gmp manufacturing of therapeutic-grade biologics on a timescale of hours. the device couples the in vitro translation of target proteins from ribosomal dna, using extracts from reconstituted lyophiliz ...201831015674
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
collaborative study of thresholds for mutagens: proposal of a typical protocol for detection of hormetic responses in cytotoxicity tests.according to the linear no-threshold model (lnt), even the smallest amount of radiation is hazardous. although the lnt is not based on solid data, this hypothesis has been applied to mutagens and carcinogens. as a result, it has been postulated that there are no thresholds for these chemicals. to demonstrate negativity by experiments is practically impossible, because negative data may leave behind the possibility that additional data might make the resolution power high enough to change negativ ...201830338768
cellular responses of hyaluronic acid-coated chitosan nanoparticles.in recent years, nanotechnology has been proven to offer promising biomedical applications for in vivo diagnostics and drug delivery, stressing the importance of thoroughly investigating the biocompatibility of potentially translatable nanoparticles (nps). herein, we report the cellular responses of uncoated chitosan nps (cs nps) and hyaluronic acid-coated chitosan nps (ha-cs nps) when introduced into chinese hamster ovary cells (cho-k1) in a dose-dependent manner (2.5, 0.25, 0.025, 0.0025, and ...201830310671
single intense microsecond electric pulse induces radiosensitization to ionizing radiation: effects of time intervals between electric pulse and ionizing irradiation.background and objective: recent studies have shown the potential of electroporation (ep) as a physical radiosensitizer for ionizing radiation (ir). the amount of sensitizing effect depends on some factors the most important of them is the time interval between the ep and ir. this experimental in vitro study aims to investigate the radiosensitizing effect of ep exposure prior to ir and also evaluate the effects of ep-ir time intervals on the amount of radiosensitizing effects. methods: chinese h ...201830319980
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
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
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
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
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 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
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
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
nanosecond range electric pulse application as a non-viral gene delivery method: proof of concept.current electrotransfection protocols are well-established for decades and, as a rule, employ long micro-millisecond range electric field pulses to facilitate dna transfer while application of nanosecond range pulses is limited. the purpose of this paper is to show that the transfection using ultrashort pulses is possible by regulating the pulse repetition frequency. we have used 200 ns pulses (10-18 kv/cm) in bursts of ten with varied repetition frequency (1 hz-1 mhz). the chinese hamster ovary ...201830341389
cytotoxic and genotoxic potential of the type i photoinitiators bapo and tpo on human oral keratinocytes and v79 fibroblasts.phenylbis(acyl) phosphine oxide (bapo) and diphenyl(acyl) phosphine oxide (tpo) are alternative photoinitiators to camphorquinone (cq) in dental resinous materials. aim of this study was to investigate their cytotoxic/genotoxic potential in human oral keratinocytes (okf6/tert2) and chinese hamster lung fibroblasts (v79) in comparison to cq.201830340767
febrile temperature elevates the expression of phosphatidylserine on plasmodium falciparum (fcr3csa) infected red blood cell surface leading to increased cytoadhesion.during the asexual intra-erythrocytic cycle, plasmodium (p.) falciparum exports parasitic proteins to the surface of infected red blood cells (irbcs) facilitating its cytoadhesion to various endothelial host receptors. this adhesive behavior is a critical contributor towards disease manifestation. however, little is known about the influence of recurring elevated temperature - a common symptom of the malaria infection - on the adhesive properties of irbcs to endothelial receptors. to address thi ...201830302009
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
characterization of cellular states of cho-k1 suspension cell culture through cell cycle and rna-sequencing profiling.chinese hamster ovary (cho) derived cell lines are the preferred host system for the production of therapeutic proteins. the aim of this work was to explore the regulation of suspension-adapted cho-k1 host cell line bioprocesses, especially under a temperature gradient from 37 °c to 31 °c. we analyzed cell cycle behavior through flow cytometry of propidium iodide stained cells and high throughput transcriptome dynamics by rna sequencing. we found a cell culture state characterized by g0/g1 synch ...201830243609
versatile cell-free protein synthesis systems based on chinese hamster ovary cells.we present an alternative production platform for the synthesis of complex proteins. apart from conventionally applied protein production using engineered mammalian cell lines, this protocol describes the preparation and principle of cell-free protein synthesis systems based on cho cell lysates. the cho cell-free system contains endogenous microsomes derived from the endoplasmic reticulum, which enables a direct integration of membrane proteins into a nature like milieu and the introduction of p ...201830242694
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
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
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
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
application of the crispr/cas9 gene editing method for modulating antibody fucosylation in cho cells.genetic engineering plays an essential role in the development of cell lines for biopharmaceutical manufacturing. advanced gene editing tools can improve both the productivity of recombinant cell lines as well as the quality of therapeutic antibodies. antibody glycosylation is a critical quality attribute for therapeutic biologics because the glycan patterns on the antibody fragment crystallizable (fc) region can alter its clinical efficacy and safety as a therapeutic drug. as an example, recomb ...201830242691
targeting mirnas with crispr/cas9 to improve recombinant protein production of cho cells.micrornas with their unique ability to target hundreds of genes have been highlighted as powerful tools to improve bioprocess behavior of cells. the common approaches to stably deplete mirnas are the use of sponge decoy transcripts or shrna inhibitors, which requires the introduction and expression of extra genetic material. as an alternative, we implemented the crispr/cas9 system in our laboratory to generate chinese hamster ovary (cho) cells which lack the expression of a specific mirna for th ...201830242690
bench-scale stirred-tank bioreactor for recombinant protein production in chinese hamster ovary (cho) cells in suspension.most pharmaceutical biotechnology companies use stirred-tank bioreactors (str) for recombinant protein manufacturing. these bioreactors are used at a variety of different scales ranging from bench to production scales, with working volumes from 10 ml to 25,000 l. bench-scale strs are commonly used to culture mammalian cells for process development, to troubleshoot production scale bioreactors using scale-down models (sdm), or to conduct fundamental research. in this chapter, we describe the oper ...201830242685
investigating dependencies of relative biological effectiveness for proton therapy in cancer cells.relative biological effectiveness (rbe) accounts for the differences in biological effect from different radiation types. the rbe for proton therapy remains uncertain, as it has been shown to vary from the clinically used value of 1.1. in this work we investigated the rbe of protons and correlated the biological differences with the underlying physical quantities.201830159358
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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