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a class of low-cost alternatives to kifunensine for increasing high mannose n-linked glycosylation for monoclonal antibody production in chinese hamster ovary cells.n-linked glycosylation of therapeutic monoclonal antibodies is an important product quality attribute for drug safety and efficacy. an increase in the percent of high mannose n-linked glycosylation may be required for drug efficacy or to match the glycosylation profile of the innovator drug during the development of a biosimilar. in this study, the addition of several chemical additives to a cell culture process resulted in high mannose n-glycans on monoclonal antibodies produced by chinese hams ...202032888259
licochalcone a, a licorice flavonoid: antioxidant, cytotoxic, genotoxic, and chemopreventive potential.licochalcone a (licoa) is a flavonoid derived from glycyrrhiza spp. plants. the present study aimed to investigate the antioxidant, cytotoxic, genotoxic, and chemopreventive effects of licoa in in vitro and in vivo systems. the results showed that licoa (197.1 μm) scavenged 77.92% of free radicals. concentrations of 147.75 µm or higher licoa produced cytotoxicity in chinese hamster ovary (cho) fibroblasts. licoa treatments of 4.43 to 10.34 µm did not exert genotoxic activity, but at 11.8 µm sign ...202032886024
effect of the disulfide isomerase pdia4 on the antibody production of chinese hamster ovary cells.therapeutic monoclonal antibodies recognize and bind specific molecules on the surface of target cells, stimulating the immune system, which can attack these targeted cells. these antibodies are produced by mammalian cells, including chinese hamster ovary (cho) cells, because the formation of antibodies requires complicated posttranslational modifications, including peptidyl-prolyl cis/trans isomerization, disulfide bond formation, and glycosylation. currently, it is thought that the efficient p ...202032878739
modeling the effect of amino acids and copper on monoclonal antibody productivity and glycosylation: a modular approach.in manufacturing monoclonal antibodies (mabs), it is crucial to be able to predict how process conditions and supplements affect productivity and quality attributes, especially glycosylation. supplemental inputs, such as amino acids and trace metals in the media, are reported to affect cell metabolism and glycosylation; quantifying their effects is essential for effective process development. we aim to present and validate, through a commercially relevant cell culture process, a technique for mo ...202032875683
congenital fibrinogen disorder with a compound heterozygote possessing two novel fgb mutations, one qualitative and the other quantitative.congenital fibrinogen disorders result from genetic mutations in fga, fgb, or fgg resulting in quantitative fibrinogen deficiencies (afibrinogenemia or hypofibrinogenemia) or qualitative fibrinogen deficiencies (dysfibrinogenemia). hypodysfibrinogenemia sharing features with hypo- and dysfibrinogenemia is rare. we performed genetic and functional analyses of a 31-year-old woman with suspected hypodysfibrinogenemia.202032871307
evaluation on elongation factor 1 alpha of entamoeba histolytica interaction with the intermediate subunit of the gal/galnac lectin and actin in phagocytosis.entamoeba histolytica is the causative agent of amoebiasis. this disease results in 40,000 to 100,000 deaths annually. the pathogenic molecules involved in the invasion of trophozoites had been constantly being clarified. this study explored the role of elongation factor 1 alpha (ef1a) in e. histolytica pathogenicity. biolayer interferometry binding and pull-down assays suggest that ef1a and intermediate subunit of lectin (igl) binding are specific. submembranous distribution of ef1a closely ali ...202032867020
'omics driven discoveries of gene targets for apoptosis attenuation in cho cells.chinese hamster ovary (cho) cells are widely used in biopharmaceutical production. improvements to cell lines and bioprocesses are constantly being explored. one of the major limitations of cho cell culture is that the cells undergo apoptosis, leading to rapid cell death, which impedes reaching high recombinant protein titres. while several genetic engineering strategies have been successfully employed to reduce apoptosis, there is still room to further enhance cho cell lines performance. 'omics ...202032865815
antimicrobial evaluation of neutral and cationic iridium(iii) and rhodium(iii) aminoquinoline-benzimidazole hybrid complexes.a series of neutral and cationic ir(iii) and rh(iii) aminoquinoline-benzimidazole hybrid complexes were synthesised and their inhibitory activities evaluated against plasmodium falciparum and mycobacterium tuberculosis. in general, the hybrid complexes display good activity against the chloroquine-sensitive nf54 strain of p. falciparum. the neutral ir(iii)- and rh(iii)-cp∗ complexes were the most active (ic50 = 0.488 μm for iriii), maintaining activity against the multidrug-resistant k1 strain. ...202032861176
enrichment of microsomes from chinese hamster ovary cells by subcellular fractionation for its use in proteomic analysis.chinese hamster ovary cells have been the workhorse for the production of recombinant proteins in mammalian cells. since biochemical, cellular and omics studies are usually affected by the lack of suitable fractionation procedures to isolate compartments from these cells, differential and isopycnic centrifugation based techniques were characterized and developed specially for them. enriched fractions in intact nuclei, mitochondria, peroxisomes, cis-golgi, trans-golgi and endoplasmic reticulum (e ...202032841274
implications of rng140 (caprin2)-mediated translational regulation in eye lens differentiation.regulation of gene expression at the translational level is key to determining cell fate and function. an rna-binding protein, rng140 (caprin2), plays a role in eye lens differentiation and has been reported to function in translational regulation. however, the mechanism and its role in eyes has remained unclear. here, we show that rng140 binds to the translation initiation factor eukaryotic initiation factor 3 (eif3) and suppresses translation through mechanisms involving suppression of eif3-de ...202032839273
an internal amino-terminal flag-tag octapeptide alters oligomerization of expressed surfactant protein-a.pulmonary surfactant protein-a (sp-a) is expressed by lung alveolar and bronchiolar epithelial cells and plays a critical role in innate immunity of the lung. exposure of the lung to various environmental insults alters sp-a homeostasis. to investigate the cellular mechanisms involved in these alterations, we added the flag octapeptide (dykddddk) to the carboxy-terminus (sp-a/c-flag) or near the amino-terminus (sp-a/n-flag) of mouse sp-a (wt-sp-a) to tag specific pools of protein. we hypothesize ...202032835791
multicopy targeted integration for accelerated development of high-producing chinese hamster ovary cells.the ever-growing biopharmaceutical industry relies on the production of recombinant therapeutic proteins in chinese hamster ovary (cho) cells. the traditional timelines of cho cell line development can be significantly shortened by the use of targeted gene integration (ti). however, broad use of ti has been limited due to the low specific productivity (qp) of ti-generated clones. here, we show a 10-fold increase in the qp of therapeutic glycoproteins in cho cells through the development and opti ...202032835482
biological properties of yeast-based mannoprotein for prospective biomedical applications.natural products constitute more than half of all biomolecules lately being used in clinical settings. mannoprotein derived from the yeast cell wall has found full biotechnological applications.202032819224
genotoxic effects of etoposide, bleomycin, and ethyl methanesulfonate on cultured cho cells: analysis by gc-ms/ms and comet assay.to evaluate methods for analysis of genotoxic effects on mammalian cell lines, we tested the effect of three common genotoxic agents on chinese hamster ovary (cho) cells by single-cell gel electrophoresis (comet assay) and gas chromatography-tandem mass spectrometry (gc-ms/ms). suspension-grown cho cells were separately incubated with etoposide, bleomycin, and ethyl methanesulfonate and analyzed by an alkaline comet assay and gc-ms/ms. although dna strand breaks were detected by the comet assay ...202032802493
low-concentration staurosporine improves recombinant antibody productivity in chinese hamster ovary cells without inducing cell death.chinese hamster ovary (cho) cells are used as host cells for biopharmaceutical production, including monoclonal antibodies (mabs). arresting the cell cycle with chemical compounds is an effective approach to improve biopharmaceutical productivity. in a previous study, potential new cell cycle-arresting compounds were screened from marine-derived microorganism culture extracts, and it was suggested that staurosporine might improve mab productivity in cho cells via cell cycle arrest. the purpose o ...202032800439
gpr120 agonists for the treatment of diabetes: a patent review (2014 present).g protein-coupled receptor 120 (gpr120) is a gαq coupled gpcr specifically activated by long-chain fatty acids (lcfas). functionally, it has been identified as a member of a family of lipid-binding free fatty acid receptors including gpr40, gpr41, and gpr43. upon stimulation by lcfas, gpr120 can directly or indirectly modulate hormone secretion from the gastrointestinal tract and pancreas, and regulate lipid and/or glucose metabolism in adipose, liver, and muscle tissues. additionally, gpr120 is ...202032799609
digital twins and their role in model-assisted design of experiments.rising demands for biopharmaceuticals and the need to reduce manufacturing costs increase the pressure to develop productive and efficient bioprocesses. among others, a major hurdle during process development and optimization studies is the huge experimental effort in conventional design of experiments (doe) methods. as being an explorative approach, doe requires extensive expert knowledge about the investigated factors and their boundary values and often leads to multiple rounds of time-consumi ...202032797268
production of glycosylphosphatidylinositol-anchored proteins for vaccines and directed binding of immunoliposomes to specific cell types.liposomes are highly useful carriers for delivering drugs or antigens. the association of glycosylphosphatidylinositol (gpi)-anchored proteins to liposomes potentially enhances the immunogenic effect of vaccine antigens by increasing their surface concentration. furthermore, the introduction of a universal immunoglobulin-binding domain can make liposomes targetable to virtually any desired receptor for which antibodies exist.202032788917
exploration of alternative scaffolds for p2y14 receptor antagonists containing a biaryl core.various heteroaryl and bicyclo-aliphatic analogues of zwitterionic biaryl p2y14 receptor (p2y14r) antagonists were synthesized, and affinity was measured in p2y14r-expressing chinese hamster ovary cells by flow cytometry. given this series' low water solubility, various polyethylene glycol derivatives of the distally binding piperidin-4-yl moiety of moderate affinity were synthesized. rotation of previously identified 1,2,3-triazole attached to the central m-benzoic acid core (25) provided moder ...202032787142
expanding the activity profile of pyrido[1,2-a]benzimidazoles: synthesis and evaluation of novel n1-1-phenylethanamine derivatives against schistosoma mansoni.praziquantel is the only widely available drug to treat schistosomiasis. with very few candidates currently in the drug development pipeline, there is an urgent need to discover and develop novel antischistosomal drugs. in this regard, the pyrido[1,2-a]benzimidazole (pbi) scaffold has emerged as a promising chemotype in hit-to-lead efforts. here, we report a novel series of antischistosomal pbis with potent in vitro activity (ic50 values of 0.08-1.43 μm) against schistosoma mansoni newly transfo ...202032786285
evaluation of antibacterial and cytotoxic properties of a fluorinated diamond-like carbon coating for the development of antibacterial medical implants.peri-implant infection is a serious complication in surgical procedures involving implants. we conducted an in vitro study to determine whether the use of a fluorinated diamond-like carbon (f-dlc) coating on a titanium alloy surface can prevent peri-implant infection. after applying the f-dlc, we evaluated its antibacterial and cytotoxic properties. the coating groups, containing controlled fluorine concentrations of 5.44%, 17.43%, 24.09%, and 30%, were examined for the presence of staphylococcu ...202032784861
a comprehensive cho swath-ms spectral library for robust quantitative profiling of 10,000 proteins.sequential window acquisition of all theoretical fragment-ion spectra (swath) is a data-independent acquisition (dia) strategy that requires a specific spectral library to generate unbiased and consistent quantitative data matrices of all peptides. swath-ms is a promising approach for in-depth proteomic profiling of chinese hamster ovary (cho) cell lines, improving mechanistic understanding of process optimization, and real-time monitoring of process parameters in biologics r&d and manufacturing ...202032782267
expression of recombinant classical swine fever virus e2 glycoprotein by endogenous txnip promoter in stable transgenic cho cells.as the main immunogen that could stimulate neutralized antibody in pigs, recombinant e2 protein of csfv was expressed in cho-dhfr-cells driven by endogenous txnip promoter from chinese hamster. different fragments of txnip promoter were amplified by pcr from isolated genomic dna of cho cells and cloned into different expression vectors. compared with cmv promoter, cho-ptxnip-4-re2 (f12) cell clone with the highest yield of re2 protein was established by random insertion of the expression cassett ...202032774204
toxicity of chlorinated algal-impacted waters: formation of disinfection byproducts vs. reduction of cyanotoxins.seasonal algal blooms in surface waters can impact water quality through an input of algal organic matter (aom) to the pool of dissolved organic matter as well as the release of cyanotoxins. the formation and speciation of disinfection byproducts (dbps) during chlorination of algal-impacted waters, collected from growth of microcystis aeruginosa were studied. second-order rate constants for the reactions of microcystins (mcs) with chlorine and bromine were determined. finally, the toxicity of ch ...202032771689
cisplatin decreases enac activity contributing to renal salt wasting syndrome.cisplatin (cddp) is an important anticancer drug. a common side effect of cddp is renal salt and water-wasting syndrome (rsws). the origin of rsws is obscure. emerging evidence, though, suggests that broad inhibition of sodium transport proteins by cddp may result in decreases in tubular reabsorption, causing increases in sodium and water excretion. in this sense, cddp would be acting like a diuretic. the effect of cddp on the epithelial na+ channel (enac), which is the final arbiter fine-tuning ...202032752278
generation of fx-/- and gmds-/- chozn host cell lines for the production of afucosylated therapeutic antibodies.antibody-dependent cellular cytotoxicity (adcc) is the primary mechanism of actions for several marketed therapeutic antibodies (mabs) and for many more in clinical trials. the adcc efficacy is highly dependent on the ability of therapeutic mabs to recruit effector cells such as natural killer cells, which induce the apoptosis of targeted cells. the recruitment of effector cells by mabs is negatively affected by fucose modification of n-glycans on the fc; thus, utilization of afucosylated mabs h ...202032748555
sensitivity of a per.c6® cell line to bis(2,4-di-tert-butylphenyl)phosphate and evaluation of a new, biocompatible single-use film.single-use technologies have brought numerous advantages to the biopharmaceutical industry. in particular, single-use bags made from multi-layered polymeric films have been adopted for cell culture and liquid handling operations in place of traditional stainless-steel systems. despite the advantages, leachable compounds originating from the film's materials of construction present a new challenge. in 2013, bis(2,4-di-tert-butylphenyl)phosphate (bdtbpp) was identified as a common leachable from s ...202032748552
a general evidence-based sequence variant control limit for recombinant therapeutic protein development.sequence variants (svs) resulting from unintended amino acid substitutions in recombinant therapeutic proteins have increasingly gained attention from both regulatory agencies and the biopharmaceutical industry given their potential impact on efficacy and safety. with well-optimized production systems, such sequence variants usually exist at very low levels in the final protein products due to the high fidelity of dna replication and protein biosynthesis process in mammalian expression systems s ...202032744138
roles of lys191 and lys179 in regulating thermodynamic binding forces of ligands to determine their binding affinity for human histamine h1 receptors.docking simulations based on the crystal structure of human histamine h1 receptors have predicted crucial roles of lys1915.39 and lys179ecl2, which exist at the entrance of the ligand-binding pocket, in increasing the h1-receptor selectivity for carboxylated second-generation antihistamines via electrostatic interaction. in this study, we evaluated the roles of lys1915.39 and lys179ecl2 in regulating the thermodynamic binding forces of non-carboxylated and carboxylated antihistamines that determ ...202032738199
a novel dextran-grafted tetrapeptide resin for antibody purification.short peptide biomimetic affinity chromatography as a novel antibody separation chromatography is a potential alternative to protein a chromatography. however, if directly attaching ligand to matrix, the adsorption capacity and mass transfer rate would be affected by pore blockage and steric effect. grafting resin is an effective method to solve this problem by using polymer as a bridge between matrix and ligand. in this work, a novel resin was prepared by grafting a tetrapeptide to the dextran- ...202032729191
the identification of nuclear αvβ3 integrin in ovarian cancer: non-paradigmal localization with cancer promoting actions.nuclear translocation of transmembrane proteins was reported in high-grade serous ovarian cancer (hgsoc), a highly aggressive gynecological malignancy. although the membrane receptor αvβ3 integrin is amply expressed in hgsoc and involved in disease progression, its nuclear localization was never demonstrated. nuclear αvβ3 was explored in hgsoc cells (ovcar3, kuramochi, and jhos4), nuclear localization signal (nls) modified β3 ovcar3, chinese hamster ovaries (cho-k1) and human embryonic kidney (h ...202032728020
analysis of damage-associated molecular pattern molecules due to electroporation of cells in vitro.background tumor cells can die via immunogenic cell death pathway, in which damage-associated molecular pattern molecules (damps) are released from the cells. these molecules activate cells involved in the immune response. both innate and adaptive immune response can be activated, causing a destruction of the remaining infected cells. activation of immune response is also an important component of tumor treatment with electrochemotherapy (ect) and irreversible electroporation (ire). we thus expl ...202032726295
synthesis and biological evaluation of antibody drug conjugates based on an antibody expression system: conamax.antibody production for adcs (or in general) is commonly performed by cho-based platforms and limited by volumetric productivity, expensive downstream purification, and extended optimization timelines. the conamax platform is a novel microbial-based protein production and secretion system. a suite of synthetic biology tools have enabled high volumetric productivity (>1 g/l/d) and glycoengineering to produce simple and consistent human-like post-translational modifications. conamax can be enginee ...202032280859
safety evaluation of water extract of gastrodia elata blume: genotoxicity and 28-day oral toxicity studies.water extract of gastrodia elata blume (wge) has great potential as an anti-depressant and could be developed as a functional food. this study aims to assess the safety of wge using in vitro and in vivo genotoxicity assays and a 28-day oral toxicity study. results from a bacterial reverse mutation assay (ames test) using five salmonella typhimurium strains (ta98, ta100, ta102, ta1535, and ta1537) with or without metabolic activation (s9 system) showed that wge did not induce mutagenicity. nor di ...202032278877
changes of resurgent na+ currents in the nav1.4 channel resulting from an scn4a mutation contributing to sodium channel myotonia.myotonia congenita (mc) is a rare disorder characterized by stiffness and weakness of the limb and trunk muscles. mutations in the scn4a gene encoding the alpha-subunit of the voltage-gated sodium channel nav1.4 have been reported to be responsible for sodium channel myotonia (scm). the nav1.4 channel is expressed in skeletal muscles, and its related channelopathies affect skeletal muscle excitability, which can manifest as scm, paramyotonia and periodic paralysis. in this study, the missense mu ...202032276507
assessing additivity of cytotoxicity associated with disinfection byproducts in potable reuse and conventional drinking waters.recent studies used the sum of the measured concentrations of individual disinfection byproducts (dbps) weighted by their chinese hamster ovary (cho) cell cytotoxicity lc50 values to estimate the dbp-associated cytotoxicity of disinfected waters. this approach assumed that cytotoxicity was additive rather than synergistic or antagonistic. in this study, we evaluated whether this assumption was valid for mixtures containing dbps at the concentration ratios measured in authentic disinfected waters ...202032275830
the effect of amino acid supplementation in an industrial chinese hamster ovary process.the main goal in biosimilar development is to increase chinese hamster ovary (cho) viability and productivity while maintaining product quality. despite media and feed optimization during process development, depletion of amino acids still occurs. the aim of the work was to optimize an existing industrial fed batch process by preventing shortage of amino acids and to gather knowledge about cho metabolism. several process outputs were evaluated such as cell metabolism, cell viability, monoclonal ...202032274904
temperature down-shift modifies expression of upr-/erad-related genes and enhances production of a chimeric fusion protein in cho cells.low culture temperature enhances the cell-specific productivity of chinese hamster ovary (cho) cells expressing varied recombinant (r-) proteins, but the mechanisms remain unclear. regulation of unfolded protein response (upr) pathway genes, such as transcriptional regulatory factors and endoplasmic reticulum (er)-resident proteins, appear to be involved in the improvements of r-protein production under low temperature conditions. the transcriptional regulation of upr-specific targets is studied ...202032271992
a proteomic approach towards understanding crypoprotective action of me2so on the cho cell proteome.chinese hamster ovary (cho) cell lines are the most widely used in vitro cells for research and production of recombinant proteins such as rhgh, tpa, and erythropoietin. we aimed to investigate changes in protein profiles after cryopreservation using 2d-dige maldi-tof ms and network pathway analysis. the proteome changes that occur in cho cells between freshly prepared cells and cryopreserved cells with and without me2so were compared to determine the key proteins and pathways altered during rec ...202032259523
comparison of a novel homogeneous cyclic amp assay and a luciferase assay for measuring stimulating thyrotropin-receptor autoantibodies.stimulating thyrotropin-receptor antibodies (tsab) cause graves' disease (gd). we tested a novel homogeneous fluorescent 3',5' cyclic adenine monophosphate (camp) assay for the detection of tsab in a bioassay.202032257955
antiarrhythmic mechanisms of chinese herbal medicine dingji fumai decoction.dingji fumai decoction (dfd) is used to treat ventricular arrhythmia, and it has provided a very good curative effect. however, its cellular electrophysiological mechanism is unknown.202032256664
screening of new cell cycle suppressive compounds from marine-derived microorganisms in chinese hamster ovary cells.monoclonal antibodies (mabs) are active pharmaceutical ingredients in antibody drugs, produced mainly using recombinant chinese hamster ovary (cho) cells. the regulation of recombinant cho cell proliferation can improve the productivity of heterologous proteins. chemical compound approaches for cell cycle regulation have the advantages of simplicity and ease of use in industrial processes. however, cho cells have genetic and phenotypic diversity, and the effects of such compounds might depend on ...202032253091
development of magoh protein-overexpressing hek cells for optimized therapeutic protein production.in the pharmaceutical industry, the need for high levels of protein expression in mammalian cells has prompted the search for new strategies, including technologies to obtain cells with improved mechanisms that enhance its transcriptional activity, folding, or protein secretion. chinese hamster ovary (cho) cells are by far the most used host cell for therapeutic protein expression. however, these cells produce specific glycans that are not present in human cells and therefore potentially immunog ...202032249976
tailoring translational strength using kozak sequence variants improves bispecific antibody assembly and reduces product-related impurities in cho cells.optimal production of bispecific antibodies (bsab) requires efficient and tailored co-expression and assembly of two distinct heavy and two distinct light chains. here, we describe a novel technology to modulate the translational strength of antibody chains via kozak sequence variants to produce bsab in a single cell line. in this study, we designed and screened a large kozak sequence library to identify 10 independent variants that can modulate protein expression levels from approximately 0.2 t ...202032246763
clinical immunogenicity risk assessment for a fusion protein.this document highlights some relevant factors in the assessment of immunogenicity risk of fusion protein therapeutics. our aim is to highlight specific risks associated with this type of molecule, while also aligning with general risk assessment factors, through a hypothetical case study, where the therapeutic molecule of interest is a receptor-fc fusion protein (rff) expressed within a typical manufacturing process in chinese hamster ovary cells (cho). given that the components are comprised o ...202032246297
reduction of charge variants by cho cell culture process optimization.over the past decade, global interest in the development of therapeutic monoclonal antibodies (mabs) has risen rapidly. as therapeutic agents, antibodies have shown marked efficacy in combatting a range of cancers and immune diseases with high target specificity and low toxicity (carla lucia et al. in plos one 6:e24071, 2011; donaghy in mabs 8:659-671, 2016; nasiri et al. in j cell physiol 9:6441-6457, 2018; teo et al. in cancer immunol immunother 61:2295-2309, 2012). recent advances in cell cul ...202032236800
a role of heparan sulphate proteoglycan in the cellular uptake of lipocalins ß-lactoglobulin and allergen fel d 4.lipocalins, small extracellular hydrophobic molecule carriers, can be internalized by a variety of different cells. however, to date receptors have only been identified for human lipocalins. here, we specifically investigated uptake mechanisms for lipocalins ß-lactoglobulin and fel d 4 in hela and chinese hamster ovary (cho) cells. we provide evidence that cell surface heparan sulphate proteoglycan is essential for internalization of these lipocalins. in hela cells, lipocalin uptake was inhibite ...202032229688
improved identification of host cell proteins in a protein biopharmaceutical by lc-ms/ms using the proteominer™ enrichment kit.host cell proteins (hcps) in biotherapeutics can be identified by the use of enzymatic digestion and lc-ms/ms analysis. however, the major challenge is that hcps are often present at very low levels in relation to the protein drug (low ppm-levels). in this study, the proteominer™ enrichment kit (bio-rad) was evaluated as a strategy to enable identification of hcps by lc-ms/ms by enrichment of low-abundant hcps and a simultaneous depletion of the high-abundant product protein. a recombinant prote ...202032229402
immunogenic and inflammatory responses to citrullinated proteins are enhanced following modification with malondialdehyde-acetaldehyde adducts.malondialdehyde-acetaldehyde adducts (maa) act as potent immune adjuvants and co-localize with citrullinated antigens in tissues effected by rheumatoid arthritis (ra). we sought to examine the role of maa-adducts in promoting ra-related autoimmunity and inflammation.202032224441
nutrient supplementation strategy improves cell concentration and longevity, monoclonal antibody production and lactate metabolism of chinese hamster ovary cells.a careful selection of culture mediums and feeds has become necessary to maximize yields of recombinant proteins during bioprocesses of mammalian cells. supplements contain a variety of concentrate nutrients, and their beneficial effects vary according to recombinant cell lines. in this study, the effects of powerfeed a on growth kinetics, productivity and cellular metabolism were evaluated for two chinese hamster ovary cell lines producing a monoclonal antibody in a batch culture. supplemented ...202032223359
a new class of quadruplex dna-binding nickel schiff base complexes.we have prepared six new nickel schiff base complexes via reactions of substituted benzophenones with different diamines in the presence of nickel(ii). these new complexes were then reacted with 1-(2-choroethyl)piperidine to afford a further six novel nickel(ii) schiff base complexes bearing pendant ethylpiperidine groups. the complexes bearing the ethylpiperidine moieties had greater solubility in water, and were therefore suitable for use in dna binding experiments. esi mass spectra of solutio ...202032219227
validation and identification of reference genes in chinese hamster ovary cells for fc-fusion protein production.in order to reveal potential genotype-phenotype relationship, rt-qpcr reactions are frequently applied which require validated and reliable reference genes. with the investigation on long-term passage and fed-batch cultivation of cho cells producing an fc-fusion protein, four new reference genes-akr1a1, gpx1, aprt, and rps16, were identified from 20 candidates with the aid of genorm, normfinder, bestkeeper, and δct programs and methods. this article provided more verified options in reference ge ...202032216463
pharmacological properties of whale shark (rhincodon typus) melanocortin-2 receptor and melancortin-5 receptor: interaction with mrap1 and mrap2.in the current study, the whale shark (ws; rhincodon typus) melanocortin-2 receptor (mc2r) co-expressed with wsmrap1 in chinese hamster ovary (cho) cells could be stimulated in a dose dependent manner by acth(1-24) with an ec50 of 2.6 × 10-10 m ± 9.7 × 10-11. when the receptor was expressed alone, stimulation was only observed at [10-6 m]. a comparable increase in sensitivity to stimulation by srdes-ac-αmsh was also observed when the receptor was co-expressed with wsmrap1. in addition, co-expres ...202032213301
a metabolic network-based approach for developing feeding strategies for cho cells to increase monoclonal antibody production.chinese hamster ovary (cho) cells are the main workhorse in the biopharmaceutical industry for the production of recombinant proteins, such as monoclonal antibodies. to date, a variety of metabolic engineering approaches have been used to improve the productivity of cho cells. while genetic manipulations are potentially laborious in mammalian cells, rational design of cho cell culture medium or efficient fed-batch strategies are more popular approaches for bioprocess optimization. in this study, ...202032211960
spike protein recognition of mammalian ace2 predicts the host range and an optimized ace2 for sars-cov-2 infection.sars-cov-2 causes the recent global covid-19 public health emergency. ace2 is the receptor for both sars-cov-2 and sars-cov. to predict the potential host range of sars-cov-2, we analyzed the key residues of ace2 for recognizing s protein. we found that most of the selected mammals including pets (dog and cat), pangolin and circetidae mammals remained the most of key residues for association with s protein from sars-cov and sars-cov-2. the interaction interface between cat/dog/pangolin/chinese h ...202032201080
branched-chain amino acid catabolism promotes thrombosis risk by enhancing tropomodulin-3 propionylation in platelets.branched-chain amino acids (bcaas), essential nutrients including leucine, isoleucine, and valine, serve as a resource for energy production and the regulator of important nutrient and metabolic signals. recent studies have suggested that dysfunction of bcaa catabolism is associated with the risk of cardiovascular disease. platelets play an important role in cardiovascular disease, but the functions of bcaa catabolism in platelets remain unknown.202032200651
cytotoxicity of halogenated tyrosyl compounds, an emerging class of disinfection byproducts.halogenated amino acids and peptides are an emerging class of disinfection byproducts (dbps), having been detected in drinking water and in washed food products. however, the toxicological significance of these emerging dbps remains unclear. in this study, the cytotoxicity of eight halogenated tyrosyl compounds was investigated in chinese hamster ovary (cho) cells using real-time cell analysis (rtca). dihalogenated tyrosyl compounds are more cytotoxic than their monohalogenated analogues. the cy ...202032200635
cell-free protein synthesis: a promising option for future drug development.proteins are the main source of drug targets and some of them possess therapeutic potential themselves. among them, membrane proteins constitute approximately 50% of the major drug targets. in the drug discovery pipeline, rapid methods for producing different classes of proteins in a simple manner with high quality are important for structural and functional analysis. cell-free systems are emerging as an attractive alternative for the production of proteins due to their flexible nature without a ...202032198631
defects in galactose metabolism and glycoconjugate biosynthesis in a udp-glucose pyrophosphorylase-deficient cell line are reversed by adding galactose to the growth medium.udp-glucose (udp-glc) is synthesized by ugp2-encoded udp-glc pyrophosphorylase (ugp) and is required for glycoconjugate biosynthesis and galactose metabolism because it is a uridyl donor for galactose-1-p (gal1p) uridyltransferase. chinese hamster lung fibroblasts harboring a hypomrphic ugp(g116d) variant display reduced udp-glc levels and cannot grow if galactose is the sole carbon source. here, these cells were cultivated with glucose in either the absence or presence of galactose in order to ...202032188137
fam83g is a novel inducer of apoptosis.the family with sequence similarity 83 (fam83) protein family g (fam83g) possesses a predicted consensus phosphorylation motif for serine/threonine-protein kinase d1/protein kinase c mu (pkd1/pkcμ) at serine residue 356 (s356). in this study, overexpressed wild-type fam83g coimmunoprecipitated with pkd1/pkcμ in chinese hamster ovary (cho) cells inhibited heat shock protein 27 (hsp27) phosphorylation at s82 and reduced the living cell number. the expression of a fam83g phosphorylation-resistant m ...202032570757
construction of an expression vector mediated by the dual promoter for prokaryotic and mammalian cell expression system.the aim of this study was to construct an expression vector mediated by the dual promoter that can simultaneously drive the recombinant protein production in eukaryotic and prokaryotic cells. the prokaryotic t7 promoter and ribosome binding site (rbs) was cloned downstream of cmv promoter in the eukaryotic expression vector pires-neo, and t7 termination sequence was inserted upstream of neomycin phosphotransferase gene to generate the dual promoter vector. the enhanced green fluorescent protein ...202032564228
expanding the chinese hamster ovary cell long noncoding rna transcriptome using rnaseq.our ability to study chinese hamster ovary (cho) cell biology has been revolutionised over the last decade following the development of next generation sequencing technology and publication of reference dna sequences for cho cells and the chinese hamster. rna sequencing has not only enabled the association of transcript expression with bioreactor conditions and desirable bioprocess phenotypes but played a key role in the characterisation of protein coding and small noncoding rnas. the annotation ...202032558938
lycopene alleviates oxidative stress via the pi3k/akt/nrf2pathway in a cell model of alzheimer's disease.oxidative stress (os) plays an important role in neurodegenerative diseases such as alzheimer's disease (ad). lycopene is a pigment with potent antioxidant and anti-tumor effects. however, its potential role in central nervous system is not well-defined. the aim of this study was to investigate the effect of lycopene on the cell model of ad and determine its underlying mechanisms.202032551202
cytotoxicity and mutagenicity of narrowband uvb to mammalian cells.phototherapy using narrowband ultraviolet-b (nb-uvb) has been shown to be more effective than conventional broadband uvb (bb-uvb) in treating a variety of skin diseases. to assess the difference in carcinogenic potential between nb-uvb and bb-uvb, we investigated the cytotoxicity via colony formation assay, genotoxicity via sister chromatid exchange (sce) assay, mutagenicity via hypoxanthine phosphoribosyltransferase (hprt) mutation assay, as well as cyclobutane pyrimidine dimer (cpd) formation ...202032545288
applications of small molecules in modulating productivity and product quality of recombinant proteins produced using cell cultures.mammalian cell cultures have been used extensively for production of recombinant protein therapeutics such as monoclonal antibodies, fusion proteins and enzymes for decades. small molecules have been investigated as media supplements to improve process productivity and reduce cost of goods. those chemicals can lead to significant yield improvement through different mechanisms such as cell cycle modulation, cellular redox regulation, etc. in addition to productivity, small molecules have also bee ...202032540474
endogenous p21-dependent transgene control for cho cell engineering.numerous engineering efforts have been made in chinese hamster ovary (cho) cells for high level production of therapeutic proteins. however, the dynamic regulation of transgene expression is limited in current systems. here, we investigated the effective regulation of transgene expression in cho cells via targeted integration-based endogenous gene tagging with engineering target genes. targeted integration of egfp-human bcl-2 into the p21 locus effectively reduced the apoptosis, compared with ra ...202032539343
putative phospholipase b-like 2 is not responsible for polysorbate degradation in monoclonal antibody drug products.polysorbates (ps) are surfactants commonly added in a therapeutic protein drug product as excipients to protect proteins from denaturation and aggregation during storage, transportation, and delivery. significant degradation of ps in drug products could lead to shortened drug shelf lives and ps-degrading activity in drug products must be minimized. identification of lipases that degrade ps could lead to better process control in drug manufacturing. in 2016, phospholipase b-like 2 (plbd2) was pro ...202032534029
insulin degrading enzyme (ide) expressed by chinese hamster ovary (cho) cells is responsible for degradation of insulin in culture media.chinese hamster ovary (cho) cells cultured in serum-free chemically-defined media (cdm) are used for manufacturing of therapeutic proteins. growth factors, such as insulin are commonly utilized in manufacturing platforms to enhance cho cell viability and growth. here we report that insulin is degraded in the culture media over time mainly due to the activity of the insulin degrading enzyme (ide). insulin degradation was faster in cell lines that released more ide, which negatively impacted cell ...202032526262
functional production of human antibody by the filamentous fungus aspergillus oryzae.monoclonal antibodies (mabs) as biopharmaceuticals take a pivotal role in the current therapeutic applications. generally mammalian cell lines, such as those derived from chinese hamster ovaries (cho), are used to produce the recombinant antibody. however, there are still concerns about the high cost and the risk of pathogenic contamination when using mammalian cells. aspergillus oryzae, a filamentous fungus recognized as a gras (generally regarded as safe) organism, has an ability to secrete a ...202032514366
a site-specific integration reporter system that enables rapid evaluation of crispr/cas9-mediated genome editing strategies in cho cells.targeted gene knockout and site-specific integration (ssi) are powerful genome editing techniques to improve the development of industrially relevant chinese hamster ovary (cho) cell lines. however, past efforts to perform ssi in cho cells are characterized by low efficiencies. moreover, numerous strategies proposed to boost ssi efficiency in mammalian cell types have yet to be evaluated head to head or in combination to appreciably boost efficiencies in cho. to enable systematic and rapid optim ...202032500600
detrimental effect of zwitterionic buffers on lysosomal homeostasis in cell lines and ipsc-derived neurons.good's buffers are commonly used for cell culture and, although developed to have minimal to no biological impact, they cause alterations in cellular processes such as autophagy and lysosomal enzyme activity. using chinese hamster ovary cells and induced pluripotent stem cell-derived neurons, this study explores the effect of zwitterionic buffers, specifically hepes, on lysosomal volume and ca2+ levels. certain zwitterionic buffers lead to lysosomal expansion and reduced lysosomal ca2+. care sho ...202032490352
harnessing the potential of artificial neural networks for predicting protein glycosylation.kinetic models offer incomparable insight on cellular mechanisms controlling protein glycosylation. however, their ability to reproduce site-specific glycoform distributions depends on accurate estimation of a large number of protein-specific kinetic parameters and prior knowledge of enzyme and transport protein levels in the golgi membrane. herein we propose an artificial neural network (ann) for protein glycosylation and apply this to four recombinant glycoproteins produced in chinese hamster ...202032489858
excito-repellency and biological safety of β-caryophyllene oxide against aedes albopictus and anopheles dirus (diptera: culicidae).the activity of β-caryophyllene oxide as either a contact or noncontact repellent was evaluated against two laboratory strains (aedes albopictus and anopheles dirus) using an excito-repellency test system. n, n-diethyl-3-methylbenzamide (deet) was used as a standard reference baseline for comparative purposes. β-caryophyllene oxide and deet were tested at concentrations of 0.1, 0.25, 0.5 and 1.0% (v/v). in addition, the phototoxic and genotoxic effects of β-caryophyllene oxide were investigated ...202032485168
process optimization using high throughput automated micro-bioreactors in chinese hamster ovary cell cultivation.optimization of bioprocesses to increase the yield of desired products is of importance in the biopharmaceutical industry. this can be achieved by strain selection and by developing bioprocess parameters. shake flasks have been used for this purpose. they, however, lack the capability to control the process parameters such as ph and dissolved oxygen (do). this limitation can be overcome with the help of an automated micro-bioreactor. these bioreactors mimic cultivation at a larger scale. one of ...202032478715
activation of oxytocin neurons improves cardiac function in a pressure-overload model of heart failure.this work shows long-term restoration of the hypothalamic oxytocin (oxt) network preserves oxt release, reduces mortality, cardiac inflammation, fibrosis, and improves autonomic tone and cardiac function in a model of heart failure. intranasal administration of oxt in patients mimics the short-term changes seen in animals by increasing parasympathetic-and decreasing sympathetic-cardiac activity. this work provides the essential translational foundation to determine if approaches that mimic parav ...202032478209
synergistic and antagonistic interactions among organic and metallic components of the ambient particulate matter (pm) for the cytotoxicity measured by chinese hamster ovary cells.although pm2.5 toxicity is known to be related to its chemical composition, the effect of interactions among various particles' components on the toxicity is not well explored. to understand these interactions, especially metals and organic compounds on pm2.5 cytotoxicity, we chose several redox-active substances known to be present in the ambient particles such as metals (cu, fe, and mn) and quinones [9,10-phenanthraquinone (pq), 1,2-naphthoquinone (1,2-nq), 1,4-naphthoquinone (1,4-nq), and 5-h ...202032474273
development of a proline-based selection system for reliable genetic engineering in chinese hamster ovary cells.chinese hamster ovary (cho) cells are the superior host cell culture models used for the bioproduction of therapeutic proteins. one of the prerequisites for bioproduction using cho cell lines is the need to generate stable cho cell lines with optimal expression output. antibiotic selection is commonly employed to isolate and select cho cell lines with stable expression, despite its potential negative impact on cellular metabolism and expression level. herein, we present a novel proline-based sel ...202032470293
gene editing in cho cells to prevent proteolysis and enhance glycosylation: production of hiv envelope proteins as vaccine immunogens.several candidate hiv subunit vaccines based on recombinant envelope (env) glycoproteins have been advanced into human clinical trials. to facilitate biopharmaceutical production, it is necessary to produce these in cho (chinese hamster ovary) cells, the cellular substrate used for the manufacturing of most recombinant protein therapeutics. however, previous studies have shown that when recombinant env proteins from clade b viruses, the major subtype represented in north america, europe, and oth ...202032470085
voluhemins, new inhibitors of sterol o-acyltransferase, produced by volutella citrinella bf-0440.new compounds, designated voluhemins a (1) and b (2), are isolated from the culture broth of the fungal strain volutella citrinella bf-0440 along with structurally related known nk12838 (3). spectroscopic data, including 1d and 2d nmr, elucidated their structures. compounds 1-3 have a common indoline-diterpene core and two additional isoprenyl moieties. compounds 1 and 3 contain a hemiaminal unit, while 2 is o-methylated 1. their inhibitory activities toward sterol o-acyltransferase (soat) 1 and ...202032467602
the use of site-specific recombination and cassette exchange technologies for monoclonal antibody production in chinese hamster ovary cells: retrospective analysis and future directions.chinese hamster ovary (cho) cell-based platforms are the most widely used for the biomanufacturing of complex therapeutic proteins, such as monoclonal antibodies (mabs). the development of high-producing clones that are stable and amenable to large-scale cultures is essential to advance a molecule toward clinical evaluation. nevertheless, the generation of such clones generally relies on random integration of an expression plasmid encoding the therapeutic protein gene into the host genome. the e ...202032456474
enabling speed to clinic for monoclonal antibody programs using a pool of clones for ind-enabling toxicity studies.the importance of speed to clinic for medicines that may address unmet medical needs puts pressure on product development timelines. historically, both toxicology and first-in-human clinical materials are generated using the same clonal-derived cells to ensure safety and minimize any development risks. however, cell line development with single cell cloning is time consuming, and aggravated by the time needed to screen for a lead clone based on cell line stability and manufacturability. in order ...202032449878
modulation of acid-sensing ion channels by hydrogen sulfide.acid-sensing ion channels (asics) have been implicated in many physiological and patho-physiological processes like synaptic plasticity, inflammation, pain perception, stroke-induced brain damage and, drug-seeking behaviour. although asics have been shown to be modulated by gasotransmitters like nitric oxide (no), their regulation by hydrogen sulfide (h2s) is not known. here, we present strong evidence that h2s potentiates asics-mediated currents. low ph-induced current in chinese hamster ovary ...202032446393
production of integrin αiibβ3 in stably transfected and clonal chinese hamster ovary cells for functional and structural studies. 202032445462
impacts on product quality attributes of monoclonal antibodies produced in cho cell bioreactor cultures during intentional mycoplasma contamination events.a mycoplasma contamination event in a biomanufacturing facility can result in costly cleanups and potential drug shortages. mycoplasma may survive in mammalian cell cultures with only subtle changes to the culture and penetrate the standard 0.2-µm filters used in the clarification of harvested cell culture fluid. previously, we reported a study regarding the ability of mycoplasma arginini to persist in a single-use, perfusion rocking bioreactor system containing a chinese hamster ovary (cho) dg4 ...202032436993
overexpression of the mitochondrial pyruvate carrier reduces lactate production and increases recombinant protein productivity in cho cells.chinese hamster ovary (cho) cells are characterized by a low glucose catabolic efficiency, resulting in undesirable lactate production. here, it is hypothesized that such low efficiency is determined by the transport of pyruvate into the mitochondria. the mitochondrial pyruvate carrier (mpc), responsible for introducing pyruvate into the mitochondria, is formed by two subunits, mpc1 and mpc2. stable cho cell lines, overexpressing the genes of both subunits, were constructed to facilitate the ent ...202032436990
using metabolomics to identify cell line-independent indicators of growth inhibition for chinese hamster ovary cell-based bioprocesses.chinese hamster ovary (cho) cells are widely used for the production of biopharmaceuticals. efforts to improve productivity through medium design and feeding strategy optimization have focused on preventing the depletion of essential nutrients and managing the accumulation of lactate and ammonia. in addition to ammonia and lactate, many other metabolites accumulate in cho cell cultures, although their effects remain largely unknown. elucidating these effects has the potential to further improve ...202032429145
small intestine proteomics coupled with serum metabolomics reveal disruption of amino acid metabolism in chinese hamsters with type 2 diabetes mellitus.type 2 diabetes mellitus (t2dm) is a metabolic disorder characterized by hyperglycemia, with metabolic disturbances resulting from defects in insulin secretion, insulin resistance (ir), or both. chinese hamsters have potential value as non-obese animal models of spontaneous t2dm for studying the pathogenesis and molecular characteristics of diabetes. in this study, the molecular characteristics of the chinese hamster diabetes animal model were investigated through small intestine proteomics and ...202032428569
biomanufacturing evolution from conventional to intensified processes for productivity improvement: a case study.process intensification has shown great potential to increase productivity and reduce costs in biomanufacturing. this case study describes the evolution of a manufacturing process from a conventional processing scheme at 1000-l scale (process a, n = 5) to intensified processing schemes at both 1000-l (process b, n = 8) and 2000-l scales (process c, n = 3) for the production of a monoclonal antibody by a chinese hamster ovary cell line. for the upstream part of the process, we implemented an inte ...202032425110
rich production media as a platform for cho cell line development.recent cell culture media for mammalian cells can be abundantly formulated with nutrients supporting production, but such media can be limited to use in host cell culture, transfection, cell cloning, and cell growth under the low cell density conditions. in many cases, appropriate platform media are used for cell line development, and then replaced with rich media for production. in this study, we demonstrate rich chemically defined media for chinese hamster ovary (cho) cells that are suitable a ...202032415509
atypical chemokine receptor ackr2-v41a has decreased ccl2 binding, scavenging, and activation, supporting sustained inflammation and increased alzheimer's disease risk.a recent genome-wide association study (gwas) of 59 cerebrospinal fluid (csf) proteins with a connection to alzheimer's disease (ad) demonstrated an association between increased levels of chemokine ligand 2 (ccl2) with an atypical chemokine receptor chemokine-binding protein 2 variant v41a (ackr2-v41a; rs2228467). high levels of ccl2 are associated with increased risk of ad development as well as other inflammatory diseases. in this study we characterized the biological function of the ackr2-v4 ...202032415244
cellular reference materials for dna damage using electrochemical oxidation.reference materials are needed to quantify the level of dna damage in cells, to assess sources of measurement variability and to compare results from different laboratories. the comet assay (single cell gel electrophoresis) is a widely used method to determine dna damage in the form of strand breaks. here we examine the use of electrochemical oxidation to produce dna damage in cultured mammalian cells and quantify its percentage using the comet assay. chinese hamster ovary (cho) cells were grown ...202032411438
proteoglycan-dependent endo-lysosomal fusion affects intracellular survival of salmonella typhimurium in epithelial cells.proteoglycans (pgs) are glycoconjugates which are predominately expressed on cell surfaces and consist of glycosaminoglycans (gags) linked to a core protein. an initial step of gags assembly is governed by the β-d-xylosyltransferase enzymes encoded in mammals by the xylt1/xylt2 genes. pgs are essential for the interaction of a cell with other cells as well as with the extracellular matrix. a number of studies highlighted a role of pgs in bacterial adhesion, invasion, and immune response. in this ...202032411142
chromosome-scale scaffolds for the chinese hamster reference genome assembly to facilitate the study of the cho epigenome.the chinese hamster genome serves as a reference genome for the study of chinese hamster ovary (cho) cells, the preferred host system for biopharmaceutical production. recent re-sequencing of the chinese hamster genome resulted in the refseq picr meta-assembly, a set of highly accurate scaffolds that filled over 95% of the gaps in previous assembly versions. however, these scaffolds did not reach chromosome-scale due to the absence of long-range scaffolding information during the meta-assembly p ...202032410221
the relation of bleomycin delivery efficiency to microbubble sonodestruction and cavitation spectral characteristics.the concurrent assessment of principal sonoporation factors has been accomplished in a single systemic study. microbubble sonodestruction dynamics and cavitation spectral characteristics, ultrasound scattering and attenuation, were examined in relation to the intracellular delivery of anticancer drug, bleomycin. experiments were conducted on chinese hamster ovary cells coadministered with sonovue microbubbles. detailed analysis of the scattering and attenuation temporal functions culminated in q ...202032385397
receptor-targeted photodynamic therapy of glucagon-like peptide 1 receptor-positive lesions.treatment of hyperinsulinemic hypoglycemia is challenging. surgical treatment of insulinomas and focal lesions in congenital hyperinsulinism is invasive and carries major risks of morbidity. medication to treat nesidioblastosis and diffuse congenital hyperinsulinism has varying efficacy and causes significant side effects. here, we describe a novel method for therapy of hyperinsulinemic hyperglycemia, highly selectively killing β-cells by receptor-targeted photodynamic therapy (rtpdt) with exend ...202032385165
effects of gentiana delavayi flower extract on app processing in app/ps1 cho cells.gentiana delavayi franch. (gentianaceae) as an ethnomedicinal plant contains a variety of effective active ingredients and exhibits diverse pharmacological actions, such as hepatoprotective, anti-inflammatory and central nervous system effects. in this study we investigated the influence of g. delavayi flower extract on amyloid precursor protein (app) processing at molecular and cellular levels. app/ps1 chinese hamster ovary (cho) cells were treated with chloroform extract of g. delavayi flower ...202032378555
expression vector cassette engineering for recombinant therapeutic production in mammalian cell systems.human tissue plasminogen activator was the first recombinant therapy protein that successfully produced in chinese hamster ovary cells in 1986 and approved for clinical use. since then, more and more therapeutic proteins are being manufactured in mammalian cells, and the technologies for recombinant protein production in this expression system have developed rapidly, with the optimization of both upstream and downstream processes. one of the most promising strategies is expression vector cassett ...202032372203
one-step enrichment of intact glycopeptides from glycoengineered chinese hamster ovary cells.recently, the glycoproteomic analysis of intact glycopeptides has emerged as an effective approach to decipher the glycan modifications of glycoproteins at the site-specific level. a rapid method to enrich intact glycopeptides is essential for the analysis of glycoproteins, especially for biopharmaceutical proteins. in this study, we established a one-step method for the rapid capture of intact glycopeptides for analysis by mass spectrometry. compared to the conventional sequential enrichment me ...202032363175
an efficient screening system in yeast to select a hyperactive piggybac transposase for mammalian applications.as non-viral transgenic vectors, the piggybac transposon system represents an attractive tool for gene delivery to achieve a long-term gene expression in immunotherapy applications due to its large cargo capacity, its lack of a trace of transposon and of genotoxic potential, and its highly engineered structure. however, further improvements in transpose activity are required for industrialization and clinical applications. herein, we established a one-plasmid effective screening system and a two ...202032357554
kcnq1 antibodies for immunotherapy of long qt syndrome type 2.patients with long qt syndrome (lqts) are predisposed to life-threatening arrhythmias. a delay in cardiac repolarization is characteristic of the disease. pharmacotherapy, implantable cardioverter-defibrillators, and left cardiac sympathetic denervation are part of the current treatment options, but no targeted therapy for lqts exists to date. previous studies indicate that induced autoimmunity against the voltage-gated kcnq1 k+ channels accelerates cardiac repolarization.202032354382
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