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ampulexins: a new family of peptides in venom of the emerald jewel wasp, ampulex compressa.the parasitoid wasp ampulex compressa injects venom directly into the brain and subesophageal ganglion of the cockroach periplaneta americana, inducing a seven to ten day lethargy termed hypokinesia. hypokinesia presents as a significant reduction in both escape response and spontaneous walking. we examined aminergic and peptidergic components of milked venom with hplc and maldi-tof mass spectrometry. hplc coupled with electrochemical detection confirmed presence of dopamine in milked venom, whi ...201829350905
the genotoxicity of an aqueous extract of gyejibokryeong-hwan.gyejibokryeong-hwan (guizhi fuling wan in china), a mixture of five herbal plants, is a well-known treatment for renal diseases including those associated with climacteric syndrome. however, the genotoxicity of gyejibokryeong-hwan has not yet been well established.201829357857
using titer and titer normalized to confluence are complementary strategies for obtaining chinese hamster ovary cell lines with high volumetric productivity of etanercept.the selection of clonally-derived chinese hamster ovary (cho) cell lines with the highest production rate of recombinant glycoproteins remains a big challenge during early stages of cell line development. different strategies using either product titer or product titer normalized to cell number are being used to assess suspension-adapted clones when grown statically in microtiter plates. however, no reported study so far has performed a direct head-to-head comparison of these two early reporters ...201829359860
development of novel oxazolo[5,4-d]pyrimidines as competitive cb2 neutral antagonists based on scaffold hopping.a series of novel oxazolo[5,4-d]pyrimidines was designed via a scaffold hopping strategy and synthesized through a newly developed approach. all these compounds were evaluated for their biological activity toward cb1/cb2 cannabinoid receptors, their metabolic stability in mice liver microsomes and their cytotoxicity against several cell lines. eight compounds have been identified as cb2 ligands with ki values less than 1 μm. it is noteworthy that 2-(2-chlorophenyl)-5-methyl-7-(4-methylpiperazin- ...201829360044
enhanced production of anti-pd1 antibody in cho cells through transient co-transfection with anti-apoptotic genes bcl-x l and mcl-1.apoptosis has a negative impact on the cell survival state during cell cultivation. to optimize mammalian cell culture for production of biopharmaceuticals, one of the important approaches is to extend cell life through over-expression of anti-apoptotic genes. here, we reported a cost-effective process to enhance cell survival and production of an antibody through transient co-transfection with anti-apoptotic genes bcl-x l or mcl-1 in chinese hamster ovary (cho) cells with polyethylenimine (pei) ...201829368032
opp labelling enables total protein synthesis quantification in cho production cell lines at the single-cell level.accurate measurement of global and specific protein synthesis rates becomes increasingly important, especially in the context of biotechnological applications such as process modelling or selection of production cell clones. while quantification of total protein translation across whole cell populations is easily achieved, methods that are capable of tracking population dynamics at the single-cell level are still lacking. to address this need, we applied o-propargyl-puromycin (opp) labelling to ...201829369524
development of a novel 99m tc-labelled small molecular antagonist for cxcr4 positive tumor imaging.the chemokine receptor 4 (cxcr4) has been an attractive molecular target for tumor imaging, since it is overexpressed in many tumor types and involved in tumor progression and metastasis. the purpose of this study is to examine the cxcr4 targeting properties of 99m tc-labeled amd3465, a small molecule antagonist of cxcr4. 99m tc-amd3465 was prepared in high yield (>95%) and stable in mice serum at least for 4 h. in vitro cell binding experiments were performed with cho (chinese hamster ovary), m ...201829370457
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
design and evaluation of a novel flavonoid-based radioprotective agent utilizing monoglucosyl rutin.in this study, three novel flavonoid composite materials, created by combining an aglycone [quercetin (que), hesperetin (hes) or naringenin (nar)] with monoglucosyl rutin (mgr), were designed to test for improved radioprotectivity compared with that provided by administration of mgr alone. aglycone in the mgr-composite state was highly soluble in water, compared with aglycone alone dissolved in dimethyl sulfoxide or distilled water. the antioxidant activity of the three flavonoid composites was ...201829373678
ring finger protein 145 (rnf145) is a ubiquitin ligase for sterol-induced degradation of hmg-coa reductase.cholesterol biosynthesis is tightly regulated in the cell. for example, high sterol concentrations can stimulate the degradation of the rate-limiting cholesterol biosynthesis enzyme 3-hydroxy-3-methylglutaryl-coenzyme a reductase (hmg-coa reductase, hmgcr). hmgcr is broken down by endoplasmic reticulum (er) membrane-associated protein complexes consisting of insulin-induced genes (insigs) and the e3 ubiquitin ligase gp78. here, we found that hmgcr degradation is partially blunted in chinese hams ...201829374057
in vitro genotoxicity assessment of dinitroaniline herbicides pendimethalin and trifluralin.pendimethalin and trifluralin are widely used dinitroaniline herbicides. both compounds can be found as residue levels in agricultural products. this study was conducted in order to provide necessary information for the risk assessment of pendimethalin and trifluralin. in this study, reactive oxygen species (ros) levels were measured to examine the potential of both compounds to induce oxidative damage in chinese hamster lung fibroblast (v79) cells. also, the genotoxic effects of pendimethalin a ...201829374591
eel kisspeptins: identification, functional activity, and inhibition on both pituitary lh and gnrh receptor expression.the european eel (anguilla anguilla) presents a blockade of sexual maturation at a prepubertal stage due to a deficient production of gonadotropins. we previously initiated, in the eel, the investigation of the kisspeptin system, one of the major gatekeepers of puberty in mammals, and we predicted the sequence of twokissgenes. in the present study, we cloned and sequencedkiss1andkiss2cdnas from the eel brain. the tissue distributions ofkiss1andkiss2transcripts, as investigated by quantitative re ...201729375473
preclinical characterization of three transient receptor potential vanilloid receptor 1 antagonists for early use in human intradermal microdose analgesic studies.the transient receptor potential vanilloid receptor 1 (trpv1) is a nonselective cation channel involved in the mediation of peripheral pain to the central nervous system. as such, the trpv1 is an accessible molecular target that lends itself well to the understanding of nociceptive signalling. this study encompasses preclinical investigations of three molecules with the prospect to establish them as suitable analgesic model compounds in human intradermal pain relief studies.201829377430
exploring the potential application of short non-coding rna-based genetic circuits in chinese hamster ovary cells.the majority of cell engineering for recombinant protein production to date has relied on traditional genetic engineering strategies, such as gene overexpression and gene knock-outs, to substantially improve the production capabilities of chinese hamster ovary (cho) cells. however, further improvements in cellular productivity or control over product quality is likely to require more sophisticated rational approaches to coordinate and balance cellular pathways. for these strategies to be impleme ...201829377624
mild hypothermic culture conditions affect residual host cell protein composition post-protein a chromatography.host cell proteins (hcps) are endogenous impurities, and their proteolytic and binding properties can compromise the integrity, and, hence, the stability and efficacy of recombinant therapeutic proteins such as monoclonal antibodies (mabs). nonetheless, purification of mabs currently presents a challenge because they often co-elute with certain hcp species during the capture step of protein a affinity chromatography. a quality-by-design (qbd) strategy to overcome this challenge involves identify ...201829381421
functional characterization of oligopeptide transporter 1 of dairy cows.it is well known that peptides play a vital role in the nutrition and health of dairy cows. bovine oligopeptide transporter 1 (bpept1) is involved in the peptide transport process in the gastrointestinal tracts of dairy cows. however, little information is known in the characteristics of bpept1. therefore, the purpose of this study was to characterize bpept1 functionally using a mammalian cell expression system. the uptake of radiolabeled dipeptide glycyl-sarcosine ([3h]-gly-sar) into the bpept1 ...201829387385
improving titer while maintaining quality of final formulated drug substance via optimization of cho cell culture conditions in low-iron chemically defined media.during biopharmaceutical process development, it is important to improve titer to reduce drug manufacturing costs and to deliver comparable quality attributes of therapeutic proteins, which helps to ensure patient safety and efficacy. we previously reported that relative high-iron concentrations in media increased titer, but caused unacceptable coloration of a fusion protein during early-phase process development. ultimately, the fusion protein with acceptable color was manufactured using low-ir ...201829388872
genotoxicity evaluation of so-ochim-tang-gamibang (socg), a herbal medicine.so-ochim-tang-gamibang (socg) is a traditional korean medicine frequently used for depression in the clinical field. in this study, we evaluated the potential genotoxicity of socg using three standard batteries of tests as part of a safety evaluation.201829391062
impact of cho metabolism on cell growth and protein production: an overview of toxic and inhibiting metabolites and nutrients.for over three decades, chinese hamster ovary (cho) cells have been the chosen expression platform for the production of therapeutic proteins with complex post-translational modifications. however, the metabolism of these cells is far from perfect and optimized, and requires substantial know how and process optimization and monitoring to perform efficiently. one of the main reasons for this is the production and accumulation of toxic and growth-inhibiting metabolites during culture. lactate and ...201829393587
a novel bicistronic gene design couples stable cell line selection with a fucose switch in a designer cho host to produce native and afucosylated glycoform antibodies.the conserved glycosylation site asn297 of a monoclonal antibody (mab) can be decorated with a variety of sugars that can alter mab pharmacokinetics and recruitment of effector proteins. antibodies lacking the core fucose at asn297 (afucosylated mabs) show enhanced antibody-dependent cell-mediated cytotoxicity (adcc) and increased efficacy. here, we describe the development of a robust platform for the manufacture of afucosylated therapeutic mabs by engineering a chinese hamster ovary (cho) host ...201829400603
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
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
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
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
grp78 protects cho cells from ribosylation.d-ribose (rib), a reactive glycation compound that exists in organisms, abnormally increases in the urine of diabetic patients and can yield large amounts of advanced glycation end products (ages), leading to cell dysfunction. however, whether cellular proteins are sensitive to this type of glycation is unknown. in this study, we found that cellular ages accumulate in chinese hamster ovary (cho) cells with increased rib concentration and administration time. mass spectrum analysis of isolated ag ...201829410209
a quantitative pcr-based assay reveals that nucleotide excision repair plays a predominant role in the removal of dna-protein crosslinks from plasmids transfected into mammalian cells.dna-protein crosslinks (dpcs) are complex dna lesions that induce mutagenesis and cell death. dpcs are created by common antitumor drugs, reactive oxygen species, and endogenous aldehydes. since these agents create other types of dna damage in addition to dpcs, identification of the mechanisms of dpc repair is challenging. in this study, we created plasmid substrates containing site-specific dpc lesions, as well as plasmids harboring lesions that are selectively repaired by the base excision or ...201829413806
applications of proteomic methods for cho host cell protein characterization in biopharmaceutical manufacturing.chinese hamster ovary (cho) cells are the most prevalent host organism for production of recombinant therapeutic proteins, including monoclonal antibodies (mabs). regulatory guidance mandates control of the host cell protein (hcp) concentration in the production process, which remains a primary challenge. although hcp concentrations are typically measured by elisa, orthogonal proteomic methods are gaining popularity for identification and quantitation of individual hcp species. recent applicatio ...201829414072
debottlenecking protein secretion and reducing protein aggregation in the cellular host.chinese hamster ovary (cho) cells have been extensively used for industrial production of biotherapeutics. with advances in cell line development and process optimization, production levels of therapeutic proteins using the cho expression system have increased to beyond 10g per liter scale. these high-titer processes could challenge the secretory capacity of cho cells, which can result in degradation and aggregation of the protein of interest. this review discusses bottlenecks in the secretory p ...201829414073
characterization of glycoengineered anti-her2 monoclonal antibodies produced by using a silkworm-baculovirus expression system.silkworm-baculovirus expression systems are efficient means for the production of recombinant proteins that provide high expression levels and post-translational modifications. here, we characterized the stability, glycosylation pattern and antibody-dependent cell-mediated cytotoxicity activity of anti-her2 monoclonal antibodies containing native or glycoengineered mammalian-like n-glycans that were produced by using a silkworm-baculovirus expression system. compared with a monoclonal antibody p ...201829415204
comparison of the in vitro toxicological activity of various particulate matter.ultrafine particles (ufps, < 2.5 µm) in air pollutants have been identified as a major cause of respiratory diseases, since they can affect the lung alveoli through the bronchus. in particular, if toxicants such as heavy metals and polycyclic aromatic hydrocarbons (pahs) are present in ufps, they can cause diseases such as asthma, chronic obstructive pulmonary disease, and lung cancer. this study compared in vitro toxicity of various particulate matter including ufps from combustion particles of ...201829415641
"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
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
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
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
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
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
analysis of peptide ligand specificity of different insect adipokinetic hormone receptors.adipokinetic hormone (akh) is a highly researched insect neuropeptide that induces the mobilization of carbohydrates and lipids from the fat body at times of high physical activity, such as flight and locomotion. as a naturally occurring ligand, akh has undergone quite a number of amino acid changes throughout evolution, and in some insect species multiple akhs are present. akh acts by binding to a rhodopsin-like g protein-coupled receptor, which is related to the vertebrate gonadotropin-releasi ...201829439466
enhancement of glycosylation by stable co-expression of two sialylation-related enzymes on chinese hamster ovary cells.sialic acid plays important roles in stabilization and modulation of the interaction of molecules and membranes in organisms. due to its high electronegativity, sialic acid can promote binding effects of molecules and support the transportation of drugs and ions in cells. this also strengthens cells against degradation from glycosidases and proteases. hence sialic acid helps glycoproteins extend their half-lives and bioactivity. on the other hand, chinese hamster ovary (cho) cells have been wide ...201829439861
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
l-cysteine capped cdse quantum dots synthesized by photochemical route.l-cysteine capped cdse quantum dots were synthesized via photochemical route in aqueous solution under uv photo-irradiation. the as grown cdse quantum dots exhibit broad fluorescence at room temperature. the cdse quantum dots were found to be formed only through the reactions of the precursors, i.e., cd(nh3)2+4 and seso2-3 with the photochemically generated 1-hydroxy-2-propyl radicals, (ch3)2coh radicals, which are formed through the process of h atom abstraction by the photoexcited acetone from ...201829442847
in vitro antileishmanial and cytotoxicity activities of essential oils from haplophyllum tuberculatum a. juss leaves, stems and aerial parts.plants used for traditional medicine produce diverse and complex secondary metabolites exhibiting various medicinal properties. the medicinal plant haplophyllum tuberculatum is used by native people against malaria and parasitic infections.201829444667
hyaluronate coating enhances the delivery and biocompatibility of gold nanoparticles.for targeted delivery with nanoparticles (nps) as drug carriers, it is imperative that the nps are internalized into the targeted cell. surface properties of nps influence their interactions with cells. we examined the responses of retinal pigment epithelial cells, nih 3t3 fibroblast cells, and chinese hamster ovary cells to gold nanoparticles (au nps) in their nascent form as well as coated with end-thiolated hyaluronate (hs-ha). the grafting density of hs-ha on au nps was calculated based on t ...201829455984
antibody glycoengineering strategies in mammalian cells.as a key parameter impacting functional and structural heterogeneity, protein glycosylation is a critical quality attribute for antibody biotherapeutic manufacturing. the glycan patterns on recombinant antibodies, particularly on the conserved fragment crystallizable (fc) region, can have significant effects on an antibody's functional activities including clearance rate, antibody-dependent cellular cytotoxicity (adcc), complement-dependent cytotoxicity (cdc), and anti-inflammatory activity. in ...201829457629
probing lactate metabolism variations in large-scale bioreactors.lactate metabolism variations are frequently encountered in mammalian cell culture processes, especially during process scale-up. in this study, we took a multipronged approach to investigate the impact of ph, pco2 , osmolality, base addition, and mixing conditions on the observed lactate variations in a chinese hamster ovary (cho) fed-batch process at 2,000 l scale. two cultivating methods, co2 -controlled and ph-controlled, were used to decouple the individual and synergistic effects from thos ...201829464875
smad4-independent activation of tgf-β signaling by muc1 in a human pancreatic cancer cell line.pancreatic ductal adenocarcinoma (pda) has a mortality rate that nearly matches its incidence rate. transforming growth factor beta (tgf-β) is a cytokine with a dual role in tumor development switching from a tumor suppressor to a tumor promoter. there is limited knowledge of how tgf-β function switches during tumorigenesis. mucin 1 (muc1) is an aberrantly glycosylated, membrane-bound, glycoprotein that is overexpressed in >80% of pda cases and is associated with poor prognosis. in pda, muc1 pro ...201829467938
understanding biopharmaceutical production at single nucleotide resolution using ribosome footprint profiling.biopharmaceuticals such as monoclonal antibodies have revolutionised the treatment of a variety of diseases. the production of recombinant therapeutic proteins, however, remains expensive due to the manufacturing complexity of mammalian expression systems and the regulatory burden associated with administrating these medicines to patients in a safe and efficacious manner. in recent years, academic and industrial groups have begun to develop a greater understanding of the biology of host cell lin ...201829471208
genetic engineering of host organisms for pharmaceutical synthesis.pharmaceutical production hosts may be derived from almost any organism, from chinese hamster ovary (cho) cell lines to isolated actinomycetes. each host can be improved, historically only through adaptive evolution. recently, the maturation of organism engineering has expanded the available models, methods, and tools for altering host phenotypes. new tools like crispr-associated endonucleases promise to enable precise cellular reprogramming and to access previously intractable hosts. in this re ...201829471209
function of the natalisin receptor in mating of the oriental fruit fly, bactrocera dorsalis (hendel) and testing of peptidomimetics.natalisins (ntls) are conservative neuropeptides, which are only found in arthropods and are documented to regulate reproductive behaviors in insects. in our previous study, we have confirmed that ntls regulate the reproductive process in an important agricultural pest, bactrocera dorsalis (hendel). hence, in this study, to further confirm the in vivo function of ntl receptor (ntlr) and assess the potential of ntlr as an insecticide target, rna interference targeting ntlr mrna was performed. we ...201829474388
an rna-seq based transcriptomic investigation into the productivity and growth variants with chinese hamster ovary cells.chinese hamster ovary (cho) cells are widely used in producing monoclonal antibodies (mabs), however, these cell lines can show variants associated with productivity and growth. fundamental understanding of cellular mechanisms can benefit high mabs production while maintaining robust cell growth. in this study, rna sequencing (rna-seq) based approach was used to study the transcriptomic space among three mab-producing cho cell lines. a phenotypic contrast of higher productivity but lower growth ...201829476805
visualisation of intracellular production bottlenecks in suspension-adapted cho cells producing complex biopharmaceuticals using fluorescence microscopy.with the advance of complex biological formats such as bispecific antibodies or fusion proteins, mammalian expression systems often show low performance. described determining factors may be accumulation or haltering of heterologous proteins within the different cellular compartments disturbing transport or secretion. in case of the investigated bispecific antibody (bsab)-producing chinese hamster ovary (cho) cell line neither impaired transcription nor decreased translation processes were ident ...201829477386
functional characterization of recombinant snake venom rhodocytin: rhodocytin mutant blocks clec-2/podoplanin-dependent platelet aggregation and lung metastasis.essentials we generated recombinant rhodocytin that could aggregate platelets via clec-2. recombinant wild-type rhodocytin formed heterooctamer with four α- and β-subunits. asp 4 in α-subunit of rhodocytin was required for binding to clec-2. inhibitory mutant of rhodocytin blocked podoplanin-dependent hematogenous metastasis.201829488681
cell-based glycan arrays for probing glycan-glycan binding protein interactions.glycan microarrays provide a high-throughput means of profiling the interactions of glycan-binding proteins with their ligands. however, the construction of current glycan microarray platforms is time consuming and expensive. here, we report a fast and cost-effective method for the assembly of cell-based glycan arrays to probe glycan-glycan-binding protein interactions directly on the cell surface. chinese hamster ovary cell mutants with a narrow and relatively homogeneous repertoire of glycofor ...201829491407
engineering a stable cho cell line for the expression of a mers-coronavirus vaccine antigen.middle east respiratory syndrome coronavirus (mers-cov) has infected at least 2040 patients and caused 712 deaths since its first appearance in 2012, yet neither pathogen-specific therapeutics nor approved vaccines are available. to address this need, we are developing a subunit recombinant protein vaccine comprising residues 377-588 of the mers-cov spike protein receptor-binding domain (rbd), which, when formulated with the addavax adjuvant, it induces a significant neutralizing antibody respon ...201829496347
pm2.5 obtained from urban areas in beijing induces apoptosis by activating nuclear factor-kappa b.particulate matter (pm), which has adverse effects on citizen health, is a major air pollutant in beijing city. pm2.5 is an indicator of pm in urban areas and can cause serious damage to human health. many epidemiological studies have shown that nuclear factor-kappa b (nf-κb) is involved in pm2.5-induced cell injury, but the exact mechanisms are not well understood.201729502513
assessment of the predictive capacity of the optimized in vitro comet assay using hepg2 cells.evaluation of dna damage is critical during the development of new drugs because it is closely associated with genotoxicity and carcinogenicity. the in vivo comet assay to assess dna damage is globally harmonized as oecd tg 489. however, a comet test guideline that evaluates dna damage without sacrificing animals does not yet exist. the goal of this study was to select an appropriate cell line for optimization of the in vitro comet assay to assess dna damage. we then evaluated the predictivity o ...201829502738
antioxidant activity of ge-132, a synthetic organic germanium, on cultured mammalian cells.ge-132 is a synthetic organic germanium that is used as a dietary supplement. the antioxidant activity of ge-132 on cultured mammalian cells was investigated in this study. first, ge-132 cytotoxicity on mammalian cultured cells was determined by measuring lactate dehydrogenase (ldh) levels. ge-132 had no cytotoxic effect on three different cell lines. second, the cell proliferative effect of ge-132 was determined by measuring atp content of whole cells and counting them. ge-132 treatment of chin ...201829503400
the combined effect of pdx1 overexpression and shh manipulation on the function of insulin-producing cells derived from adipose-tissue stem cells.pancreatic and duodenal homeobox 1 (pdx1) and sonic hedgehog (shh) are the key regulators of beta-cell function. in vitro experiments have shown that there is significant cooperation between pdx1 and shh with regard to the production and maintenance of insulin-producing cells (ipcs). in this study, the combined effect of pdx1 overexpression and shh manipulation on the function of adipose tissue-derived ipcs was determined. a eukaryotic expression vector (pdx1- pcdna3.1(+)) was constructed and tr ...201829511614
biogenesis of silver nanoparticles using leaf extract of indigofera hirsuta l. and their potential biomedical applications (3-in-1 system).the present study reports the biosynthesis of silver nanoparticles (ih-agnps) using aqueous leaf extract of indigofera hisruta l. the biosynthesized ih-agnps were found to be fcc crystals, 5-10 nm in size, spherical in shape and stable. the biosynthesized ih-agnps showed dose-dependant cytotoxicity against prostate cancer (pc3) (ic50 = 68.5 μg/ml), colon cancer (colo205) (ic50 = 85.2 μg/ml), and mouse melanoma (b16f10) (ic50 = 80.9 μg/ml). ih-agnps were found to be nontoxic towards normal cho (c ...201829513113
role of microvesicles in the spread of herpes simplex virus type 1 in oligodendrocytic cells.herpes simplex virus type 1 (hsv-1) is a neurotropic pathogen that can infect many types of cells and establishes latent infections in neurons of sensory ganglia. in some cases, the virus spreads into the cns causing encephalitis or meningitis. cells infected with several different types of viruses may secrete microvesicles containing viral proteins and rnas. in some instances, extracellular microvesicles harboring infectious virus have been found. here we describe the features of shedding micro ...201829514899
antibacterial effect of copaifera duckei dwyer oleoresin and its main diterpenes against oral pathogens and their cytotoxic effect.this study evaluates the antibacterial activity of the copaifera duckei dwyer oleoresin and two isolated compounds [eperu-8(20)-15,18-dioic acid and polyalthic acid] against bacteria involved in primary endodontic infections and dental caries and assesses the cytotoxic effect of these substances against a normal cell line. mic and mbc assays pointed out the most promising metabolites for further studies on bactericidal kinetics, antibiofilm activity, and synergistic antibacterial action. the ole ...201829515530
a comparative study of using free radical generators in the testing of chosen oxidative stress parameters in the different types of cells.the aim of this study was to assess whether there are differences between the results of determining oxidative stress markers obtained from different origin cell lines after exposure to chemicals generating free radicals. the studies considered two markers of oxidative stress: the level of thiobarbituric acid reactive substances (tbars) and superoxide dismutase activity. the evaluation was performed in five cell lines: chinese hamster ovary (cho-9) cells, lung adenocarcinoma a549, macrophages ra ...201829519201
glyco-mapper: a chinese hamster ovary (cho) genome-specific glycosylation prediction tool.glyco-mapper is a novel systems biology product quality prediction tool created using a new framework termed: discretized reaction network modeling using fuzzy parameters (dream-zyp). within glyco-mapper, users fix the nutrient feed composition and the glycosylation reaction fluxes to fit the model glycoform to the reference experimental glycoform, enabling cell-line specific glycoform predictions as a result of cell engineering strategies. glyco-mapper accurately predicts glycoforms associated ...201829522825
protein a affinity chromatography of chinese hamster ovary (cho) cell culture broths containing biopharmaceutical monoclonal antibody (mab): experiments and mechanistic transport, binding and equilibrium modeling.protein a-based affinity chromatography is a highly-efficient separation method to capture, purify and isolate biosimilar monoclonal antibodies (mab) - an important medical product of biopharmaceutical industrial manufacturing. it is considered the most expensive step in purification downstream operations; therefore, its performance optimization offers a great cost saving in the overall production expenditure. the biochemical mixture-separating specific interaction experiments with chinese hamst ...201829522957
glyco-engineered long acting fgf21 variant with optimal pharmaceutical and pharmacokinetic properties to enable weekly to twice monthly subcutaneous dosing.pharmacological administration of fgf21 analogues has shown robust body weight reduction and lipid profile improvement in both dysmetabolic animal models and metabolic disease patients. here we report the design, optimization, and characterization of a long acting glyco-variant of fgf21. using a combination of n-glycan engineering for enhanced protease resistance and improved solubility, fc fusion for further half-life extension, and a single point mutation for improving manufacturability in chi ...201829523796
evaluating the interactions between red stingray (dasyatis akajei) melanocortin receptors and elephant shark (callorhinchus milii) mrap1 and mrap2 following stimulation with either stingray acth(1-24) or stingray des-acetyl-αmsh: a pharmacological study in chinese hamster ovary cells.previous studies on bony vertebrate mc2r orthologs (i.e., ray finned fishes, amphibians, reptiles, birds, and mammals) have shown that these mc2r orthologs have an obligatory requirement for interaction with bony vertebrate mrap1 orthologs to a) allow for the trafficking of the mc2r ortholog to the plasma membrane; and b) to allow activation by acth, but not by any msh-sized ligand. in addition, previous studies have found that co-expression of teleost and mammalian mc4r orthologs with correspon ...201829524525
comparative ecotoxicity of potential biofuels to water flea (daphnia magna), zebrafish (danio rerio) and chinese hamster (cricetulus griseus) v79 cells.the ecotoxicity of two biofuel candidates (1‑octanol and 2‑butanone) was investigated by an integrative test strategy using three bioassays: the acute immobilisation test with water flea (d. magna), the fish embryo acute toxicity test with zebrafish (danio rerio) and the in vitro micronucleus assay with chinese hamster (cricetulus griseus) v79 cells. the median effective concentration (ec50) values were 14.9±0.66mgl-1for 1‑octanol, and 2152.1±44.6mgl-1for 2‑butanone in the d. magna test. both 1‑ ...201829524897
novel hghrh homodimer promotes fertility of female infertile hamster by up-regulating ovarian ghrh receptor without triggering gh secretion.extra-hypothalamic growth hormone-releasing hormone (ghrh) plays an important role in infertility. the female infertility models were formed by intraperitoneally injecting cyclophosphamide in 5-week-old chinese hamster once in a week for 5 weeks. all the models mated with healthy male hamster in the ratio of 1:1 in the experimental 6-8th week and the couples were separated to breed in the 9-10th week. 20 mg/kg of cyclophosphamide induced temporary interference of reproduction and did not cause s ...201829526766
oxidative stress and neurodegeneration: the possible contribution of quinone reductase 2.there is increasing evidence that oxidative stress is involved in the etiology and pathogenesis of neurodegenerative disorders. overproduction of reactive oxygen species (ros) is due in part to the reactivity of catecholamines, such as dopamine, adrenaline, and noradrenaline. these molecules are rapidly converted, chemically or enzymatically, into catechol-quinone and then into highly deleterious semiquinone radicals after 1-electron reduction in cells. notably, the overexpression of dihydronico ...201829526807
protective activity of pyruvate against vanadium-dependent cytotoxicity in chinese hamster ovary (cho-k1) cells.with increasing human exposure to vanadium-containing compounds and growing concern over their impact on human health, identification of safe methods for efficient treatment of vanadium poisoning may be of value. in this study, using chinese hamster ovary (cho-k1) cells, we show that the toxicity of vanadyl sulphate (voso4) is mitigated in the presence of sodium pyruvate. the exposure of cho-k1 cells to 100 μm voso4 for 48 h induced significant cytotoxicity (measured with a resazurin assay) and ...201829529943
glycoengineering of mammalian expression systems on a cellular level.mammalian expression systems such as chinese hamster ovary (cho), mouse myeloma (ns0), and human embryonic kidney (hek) cells serve a critical role in the biotechnology industry as the production host of choice for recombinant protein therapeutics. most of the recombinant biologics are glycoproteins that contain complex oligosaccharide or glycan attachments representing a principal component of product quality. both n-glycans and o-glycans are present in these mammalian cells, but the engineerin ...201829532110
the protective effect of niacinamide on cho aa8 cell line against ultraviolet radiation in the context of main cytoskeletal proteins.niacinamide is a stable and water-soluble form of vitamin b3, a valuable and versatile cosmetic ingredient, which is well absorbed and tolerated by the skin. a large body of literature has reported on the antioxidant and cell repair properties of niacinamide. therefore, it has been shown to be useful in the protection of the skin against ultraviolet b (uvb) radiation and free radicals. despite numerous hypotheses on the mechanism of vitamin b3, its protective effects have not yet been fully eluc ...201829533537
the concept of hybrid molecules of tacrine and benzyl quinolone carboxylic acid (bqca) as multifunctional agents for alzheimer's disease.novel tacrine-benzyl quinolone carboxylic acid (tacrine-bqca) hybrids were designed based on multi-target directed ligands (mtlds) paradigm, synthesized and evaluated in vitro as inhibitors of human acetylcholinesterase (hache) and human butyrylcholinesterase (hbche). tacrine moiety is represented herein as 7-methoxytacrine, 6-chlorotacrine or unsubstituted tacrine forming three different families of seven members, i.e. 21 compounds in overall. introducing bqca, a positive modulator of m1 muscar ...201829533874
evaluation of fluorescent dyes to measure protein aggregation within mammalian cell culture supernatants.a current challenge in bioprocessing is the ability to analyse critical quality attributes such as aggregation without prior purification. this study evaluated the use of fluorescent dyes (bis-ans, sypro orange, thioflavin t and proteostat) to characterise mab aggregates in chinese hamster ovary clarified cultures.201829540956
elucidating the impact of cho cell culture media on tryptophan oxidation of a monoclonal antibody through gene expression analyses.oxidation of monoclonal antibodies (mab) is a common chemical modification with potential impact on a therapeutic protein's activity and immunogenicity. in a previous study, it was found that tryptophan oxidation (trp-ox) levels of two mab produced in chinese hamster ovary (cho) cells were significantly lowered by modifying cell culture medium/feed. in this study, transcriptome analysis by rna-seq is applied to further elucidate the underlying mechanism of those changes in lowering the trp-ox le ...201829542860
protein oxidative damage and redox imbalance induced by ionising radiation in cho cells.reactive oxygen species (ros) are important mediators of the cytotoxicity induced by the direct reaction of ionising radiation (ir) with all critical cellular components, such as proteins, lipids, and nucleic acids. the derived oxidative damage may propagate in exposed tissues in a dose- and spatiotemporal dependent manner to other cell compartments, affecting intracellular signalling, and cell fate. to understand how cell damage is induced, we studied the oxidative events occurring immediately ...201829546780
process analytical technology for advanced process control in biologics manufacturing with the aid of macroscopic kinetic modeling.productivity improvements of mammalian cell culture in the production of recombinant proteins have been made by optimizing cell lines, media, and process operation. this led to enhanced titers and process robustness without increasing the cost of the upstream processing (usp); however, a downstream bottleneck remains. in terms of process control improvement, the process analytical technology (pat) initiative, initiated by the american food and drug administration (fda), aims to measure, analyze, ...201829547557
development and validation of chemical features-based proton-coupled folate transporter/activity and reduced folate carrier/activity models (pharmacophores).all clinically used antifolates lack transport selectivity for tumors over normal cells resulting in dose-limiting toxicities. there is growing interest in developing novel tumor-targeted cytotoxic antifolates with selective transport into tumors over normal cells via the proton-coupled folate transporter (pcft) over the ubiquitously expressed reduced folate carrier (rfc). a lack of x-ray crystal structures or predictive models for pcft or rfc has hindered structure-aided drug design for pcft-se ...201829550744
chemical modification of protein a chromatography ligands with polyethylene glycol. ii: effects on resin robustness and process selectivity.we have proposed chemical modification of protein a (proa) chromatography ligands with polyethylene glycol (pegylation) as a strategy to increase the resin selectivity and robustness by providing the ligand with a steric repulsion barrier against non-specific binding. here, we report on robustness and selectivity benefits for repligen captiva primab resin with ligands modified with 5.2 kda and 21.5 kda peg chains, respectively. pegylation of proa ligands allowed the resin to retain a higher perc ...201829551237
melanin nanoparticles: antioxidant activities and effects on γ-ray-induced dna damage in the mouse.the radioprotective and antioxidant activities of melanin nanoparticles (mnp) were investigated in chinese hamster ovary (cho) cells in vitro and balb/c mice in vivo. the endpoints measured were cell viability, superoxide dismutase (sod) enzyme activity, malondialdehyde (mda) levels, dna damage (comet assay), and histopathological examination of tissues. irradiated groups showed decreased sod activity and increased mda levels. irradiation caused a 3-10-fold increase in comet parameters such as % ...201829555060
heterologous expression of three antigenic proteins from angiostrongylus cantonensis: es-7, lec-5, and 14-3-3 in mammalian cells.angiostrongylus cantonensis is a parasitic nematode and the main causative agent of human cerebral eosinophilic meningoencephalitis (eom). a definitive diagnosis of eom usually requires serologic or molecular analysis of the patient's clinical sample. currently, a 31 kda antigen is used in immunological tests for this purpose, however as a crude antigen preparation it may present cross-reactivity with other helminthic infections, especially echinococcosis. heterologous expression studies using p ...201829555232
toxicological evaluation of 6'-sialyllactose (6'-sl) sodium salt.we performed a series of toxicity studies on the safety of 6'-sialyllactose (6'-sl) sodium salt as a food ingredient. 6'-sl sodium salt, up to a maximum dose of 5000 μg/plate, did not increase the number of revertant colonies in five strains of salmonella typhimurium in the presence or absence of s9 metabolic activation. a chromosomal aberration assay (using chinese hamster lung cells) found no clastogenic effects at any concentration of 6'-sl sodium salt in the presence or absence of s9 metabol ...201829555556
human umbilical cord blood serum-derived α-secretase: functional testing in alzheimer's disease mouse models.alzheimer's disease (ad) is an age-related disorder that affects cognition. our previous studies showed that the neuroprotective fragment of amyloid procurer protein (app) metabolite, soluble appα (sappα), interferes with β-site app-cleaving enzyme 1 (bace1, β-secretase) cleavage and reduces amyloid-β (aβ) generation. in an attempt to identify approaches to restore sappα levels, we found that human cord blood serum (cbs) significantly promotes sappα production compared with adult blood serum (ab ...201829560732
inhibition of the α-subunit of phosphoinositide 3-kinase in heart increases late sodium current and is arrhythmogenic.although inhibition of phosphoinositide 3-kinase (pi3k) is an emerging strategy in cancer therapy, we and others have reported that this action can also contribute to drug-induced qt prolongation and arrhythmias by increasing cardiac late sodium current (inal). previous studies in mice implicate the pi3k-α isoform in arrhythmia susceptibility. here, we have determined the effects of new anticancer drugs targeting specific pi3k isoforms on inal and action potentials (aps) in mouse cardiomyocytes ...201829563327
mild hypothermia upregulates myc and xbp1s expression and improves anti-tnfα production in cho cells.chinese hamster ovary (cho) cells are the most frequently used host for commercial production of therapeutic proteins. however, their low protein productivity in culture is the main hurdle to overcome. mild hypothermia has been established as an effective strategy to enhance protein specific productivity, although the causes of such improvement still remain unclear. the self-regulation of global transcriptional regulatory factors, such as myc and xbp1s, seems to be involved in increased the reco ...201829566086
identification of high affinity her2 binding antibodies using cho fab surface display.discovery of monoclonal antibodies is most commonly performed using phage or yeast display but mammalian cells are used for production because of the complex antibody structure, including the multiple disulfide bonds and glycosylation, required for function. as this transition between host organisms is often accompanied by impaired binding, folding or expression, development pipelines include laborious plate-based screening or engineering strategies to adapt an antibody to mammalian expression. ...201829566240
an engineered complement factor h construct for treatment of c3 glomerulopathy.background c3 glomerulopathy (c3g) is associated with dysregulation of the alternative pathway of complement activation, and treatment options for c3g remain limited. complement factor h (fh) is a potent regulator of the alternative pathway and might offer a solution, but the mass and complexity of fh makes generation of full-length fh far from trivial. we previously generated a mini-fh construct, with fh short consensus repeats 1-5 linked to repeats 18-20 (fh1-5^18-20), that was effective in ex ...201829588430
combination of temperature shift and hydrolysate addition regulates anti-ige monoclonal antibody charge heterogeneity in chinese hamster ovary cell fed-batch culture.charge heterogeneity has been broadly studied as a critical quality attribute during monoclonal antibody (mab) production that may subsequently affect product stability and biopotency. however, the charge variation distribution is poorly controlled, so methods of more effective control need to be explored. in this study, the combined effects of temperature shift (37-34, 37-32, or 37-30 °c) and hydrolysate addition (0.100 g/l) to culture feed on the charge heterogeneity of anti-ige mab were inves ...201829589263
toxic hypf-n oligomers selectively bind the plasma membrane to impair cell adhesion capability.the deposition of fibrillar protein aggregates in human organs is the hallmark of several pathological states, including highly debilitating neurodegenerative disorders and systemic amyloidoses. it is widely accepted that small oligomers arising as intermediates in the aggregation process, released by fibrils, or growing in secondary nucleation steps are the cytotoxic entities in protein-misfolding diseases, notably neurodegenerative conditions. increasing evidence indicates that cytotoxicity is ...201829590593
mechanisms driving the lactate switch in chinese hamster ovary cells.the metabolism of chinese hamster ovary (cho) cells in a production environment has been extensively investigated. however, a key metabolic transition, the switch from lactate production to lactate consumption, remains enigmatic. though commonly observed in cho cultures, the mechanism(s) by which this metabolic shift is triggered is unknown. despite this, efforts to control the switch have emerged due to the association of lactate consumption with improved cell growth and productivity. this revi ...201829603726
multiple reaction monitoring targeted lc-ms analysis of potential cell death marker proteins for increased bioprocess control.the monitoring of protein biomarkers for the early prediction of cell stress and death is a valuable tool for process characterization and efficient biomanufacturing control. a representative set of six proteins, namely gpdh, prdx1, lgals1, cfl1, tagln2 and mdh, which were identified in a previous cho-k1 cell death model using discovery lc-mse was translated into a targeted liquid chromatography multiple reaction monitoring mass spectrometry (lc-mrm-ms) platform and verified. the universality of ...201829607450
monoclonal antibody l1mab-13 detected human pd-l1 in lung cancers.programmed cell death ligand-1 (pd-l1) is a type i transmembrane glycoprotein expressed on antigen-presenting cells. it is also expressed in several tumor cells such as melanoma and lung cancer cells. a strong correlation has been reported between human pd-l1 (hpd-l1) expression in tumor cells and negative prognosis in cancer patients. here, a novel anti-hpd-l1 monoclonal antibody (mab) l1mab-13 (igg1, kappa) was produced using a cell-based immunization and screening (cbis) method. we investigat ...201829608408
all-trans retinoic acid in combination with sodium butyrate enhances specific monoclonal antibody productivity in recombinant cho cell line.the effects of all-trans retinoic acid (ra) and sodium butyrate (nabu) on growth, viability and antibody production of two types of transfected chinese hamster ovary cell lines (cho-k1 and cho-s) were investigated using a batch mode cell culture. by adding 0.5 mm nabu in the cho-k1 cell culture, the cell specific productivity (qp) and antibody concentration increased by five- and threefold, respectively. the optimal concentration of ra was 100 nm which resulted in twofold increase in antibody pr ...201829619548
magnetic field direction differentially impacts the growth of different cell types.magnetic resonance imaging (mri) machines have horizontal or upright static magnetic field (smf) of 0.1-3 t (tesla) at sites of patients and operators, but the biological effects of these smfs still remain elusive. we examined 12 different cell lines, including 5 human solid tumor cell lines, 2 human leukemia cell lines and 4 human non-cancer cell lines, as well as the chinese hamster ovary cell line. permanent magnets were used to provide 0.2-1 t smfs with different magnetic field directions. w ...201829621414
conditions of prooxidant activity of cistus and pomegranate polyphenols in v79 cell cultures.polyphenol rich extracts obtained from cistus herb (cistus incanus l.) and pomegranate peels (punica granatunm l.) added at high concentrations (25-100 pg/ml) to v79 (chinese hamster lung fibroblast) cell cultures, markedly increased intracellular level of ros (reactive oxygen species). also in cells exposed to the exogenous oxidant - h₂0₂, [100 μm, 30 min., 37'c] intracellular ros level was augmented, although to a lower extent than in resting cells not exposed to h₂0₂. additionally, cistus and ...201729624273
antioxidant and cancer chemopreventive activities of cistus and pomegranate polyphenols.polyphenol rich extracts obtained from cistus herb (cistus incanus l.) and pomegranate peel (punica granatum l.) exhibited significant antioxidant activity in v79 cell culture (chinese hamster lung fibroblasts) -cistus extract reduced intracellular content of reactive oxygen species (ros) by 30-40% and pomegranate extract by 29-36%. in human breast (mcf-7) and colon (lovo) cancer cell lines cistus and pomegranate extracts decreased cancer cell growth both in drug-sensitive cells by 15-30% and in ...201729624275
analysis of radiation-induced chromosomal aberrations on a cell-by-cell basis after alpha-particle microbeam irradiation: experimental data and simulations.there is a continued need for further clarification of various aspects of radiation-induced chromosomal aberration, including its correlation with radiation track structure. as part of the emrp joint research project, biologically weighted quantities in radiotherapy (bioquart), we performed experimental and theoretical analyses on chromosomal aberrations in chinese hamster ovary cells (cho-k1) exposed to α particles with final energies of 5.5 and 17.8 mev (absorbed doses: ∼2.3 gy and ∼1.9 gy, re ...201829624483
assessment of genotoxic activity of oleoresins and leaves extracts of six copaifera species for prediction of potential human risks.copaifera species are used in folk medicine for a wide variety of pharmacological properties. this paper reports the cytotoxic and genotoxic analyses of oleoresins and leaves extracts of copaifera species: c. duckei, c. multijuga, c. paupera, c. pubiflora, c. reticulata and c. trapezifolia.201829625274
purification of human erythropoietin by affinity chromatography using cyclic peptide ligands.prior work described the identification and characterization of erythropoietin-binding cyclic peptides slfflh, vvffvh, fsllhh and fsllsh (all of the form cyclo[(nα-ac)dap(a)-x1-x6-ae], wherein x1-x6 is the listed sequences). in this work, the peptide ligands were synthesized on toyopearl chromatographic resins and utilized for purifying recombinant human erythropoietin (rhuepo) from complex sources. elution buffer ph and composition were optimized to maximize the recovery of standard rhuepo from ...201829625371
in situ formation of injectable chitosan-gelatin hydrogels through double crosslinking for sustained intraocular drug delivery.rapid clearance and low ocular bioavailability are drawbacks of conventional ophthalmic eye drops. to increase the ocular drug resistance time and improve efficacy, an in situ forming and thermosensitive chitosan-gelatin hydrogel was developed. the feasibility of using this hydrogel as a topical eye drop formulation for sustained release of timolol maleate was evaluated. the flexible hydrogel that was co-crosslinked with β‑glycerophosphate disodium salt hydrate (β-gd) and genipin showed a fast g ...201829636124
experimentally-induced animal models of prediabetes and insulin resistance: a review.animal models are very common in diabetes research when rodents are mostly used in this regard. although a number of animal models of type 1 and type 2 diabetes (t2d) are developed in last few decades, the numbers of animal models of prediabetes and insulin resistance are very scanty. due to the rapidly changing pathogenesis of the disease and preventive study, the popularity of the prediabetic and insulin resistance models are largely increased in the recent years. some genetically or spontaneo ...201629648707
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