Publications by authors named "Linling Yu"

24 Publications

  • Page 1 of 1

Triiodothyronine ameliorates silica-induced pulmonary inflammation and fibrosis in mice.

Sci Total Environ 2021 May 26;790:148041. Epub 2021 May 26.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Environmental exposure to silica or particles is very common in natural, agricultural and industrial activities. Chronic silica exposure can lead to silicosis, which remains one of the most serious interstitial lung diseases all through the world, while viable therapeutic choices are restricted. Triiodothyronine (T3) has been shown to exert a defensive role in many pulmonary diseases, however, rare data are available regarding the role of T3 on silica-induced injury. We constructed an experimental silicosis mouse model and T3 was intraperitoneally administrated after instillation of silica to observe the effect of T3 on silica-induced lung inflammation and fibrosis. Our results showed that the silicosis mouse model was accompanied by changes in thyroid morphology and function, and T3 supplement reduced silica-induced lung damage, inflammation and collagen deposition. The protective properties of T3 on silica-induced lung injury could be partially mediated through thyroid hormone receptors. And the mechanism by which T3 treatment ameliorated silica-induced fibrosis appeared to be via the reduction of glycolysis. Also, T3 could sufficiently postpone the progression of pulmonary fibrosis in established silicosis. Our findings reveal that administration of T3 could down-regulate the inflammatory response, pulmonary fibrosis and other lung damage caused by silica. The reduction of glycolysis may be one of the mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.148041DOI Listing
May 2021

Associations between urinary phthalate metabolite concentrations and markers of liver injury in the US adult population.

Environ Int 2021 May 6;155:106608. Epub 2021 May 6.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address:

Background: Phthalates have been largely used for years in varieties of products worldwide. However, research on the joint toxic effect of various phthalates exposure on the liver is lacking.

Objectives: We aimed to assess exposure to phthalates on liver function tests (LFTs).

Methods: This analysis included data on 6046 adults (≥20 years old) who participated in a National Health and Nutrition Examination Survey (NHANES) in 2007-2016. We employed linear regression and Bayesian kernel machine regression (BKMR), to explore the associations of urinary phthalate metabolites with 8 indicators of LFTs.

Results: Di(2-ethylhexyl) phthalate (ΣDEHP) was found to be positively associated with serum alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) (all P  < 0.05). We found significant positive associations of ∑DEHP, mono-ethyl phthalate (MEP) and mono-(carboxyisononyl) phthalate (MCNP) with total bilirubin (TBIL) (all P  < 0.05). ΣDEHP, mono-n-butyl phthalate (MBP), mono-(3-carboxypropyl) phthalate (MCPP) and mono-benzyl phthalate (MBzP) were negatively associated with serum ALB (all P  < 0.05). The BKMR analyses showed a significantly positive overall effect on ALT, AST, ALP and TBIL levels with high concentrations of phthalate metabolites and a significantly negative overall effect on ALB and TP, when all the chemicals at low concentrations.

Conclusions: Our results add novel evidence that exposures to phthalates might be adversely associated with the indicators of LTFs, indicating the potential toxic effect of phthalate exposures on the human liver.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2021.106608DOI Listing
May 2021

Preliminary study on impacts of polystyrene microplastics on the hematological system and gene expression in bone marrow cells of mice.

Ecotoxicol Environ Saf 2021 May 4;218:112296. Epub 2021 May 4.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China. Electronic address:

Microplastics (MPs) are currently a global environmental pollutants and health hazards that caused by MPs cannot be ignored. However, studies on MP toxicity in mammals are scare. Here, we investigated the effects of two doses (0.1 mg and 0.5 mg) of 5 µm polystyrene microplastic (PS-MP) particles on the hematological system of mice through traditional toxicology experiments and assessed the related potential biological mechanisms using transcriptome sequencing analysis. The toxicological examinations showed that the 0.5 mg dose significantly decreased white blood cell count, increased Pit count, and inhibited the growth of colony-forming unit CFU-G, CFU-M and CFU-GM. Compared with the control group, there were 41 differentially expressed genes (DEGs) in the 0.1 mg-treated group and 32 significantly changed genes in 0.5 mg-treated group. Of note, eight genes were found to be significantly altered in both the PS-MP-treated groups. Gene ontology analysis showed that DEGs were mainly involved in T cell homeostasis, response to osmotic stress, extracellular matrix and structure organization, and metabolic process of NADP and nucleotides. In addition, pathway analysis revealed that the Jak/Stat pathway, pentose and glucuronate interconversions, nicotinate and nicotinamide metabolism, biosynthesis of unsaturated fatty acids, and the pentose phosphate pathway were involved in PS-MP-induced toxicity in mice. These results indicated that PS-MP exposure can cause hematotoxicity to some extent, impact gene expression, and disturb related molecular and biological pathways in mouse bone marrow cells. Our study provides fundamental data on the hematotoxicity of PS-MPs in terrestrial mammals that will help to further assess the corresponding health risks in these mammals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2021.112296DOI Listing
May 2021

Recent advances in protein chromatography with polymer-grafted media.

Authors:
Linling Yu Yan Sun

J Chromatogr A 2021 Feb 5;1638:461865. Epub 2021 Jan 5.

Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China; Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China. Electronic address:

The strategy of using polymer-grafted media is effective to create protein chromatography of high capacity and uptake rate, giving rise to an excellent performance in high-throughput protein separation due to its high dynamic binding capacity. Taking the scientific development and technological innovation of protein chromatography as the objective, this review is devoted to an overview of polymer-grafted media reported in the last five years, including their fabrication routes, protein adsorption and chromatography, mechanisms behind the adsorption behaviors, limitations of polymer-grafted media and chromatographic operation strategies. Particular emphasis is placed on the elaboration and discussion on the behaviors of ion-exchange chromatography (IEC) with polymer-grafted media because IEC is the most suitable chromatographic mode for this kind of media. Recent advances in both the theoretical and experimental investigations on polymer-grafted media are discussed by focusing on their implications to the rational design of novel chromatographic media and mobile phase conditions for the development of high-performance protein chromatography. It is concluded that polymer-grafted media are suitable for development of IEC and mixed-mode chromatography with charged and low hydrophobic ligands, but not for hydrophobic interaction chromatography with high hydrophobic ligands and affinity chromatography with ligands that have single binding site on the protein.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2020.461865DOI Listing
February 2021

Protein adsorption to poly(2-aminoethyl methacrylate)-grafted Sepharose gel: Effects of chain length and charge density.

J Chromatogr A 2021 Feb 31;1638:461869. Epub 2020 Dec 31.

Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China; Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China. Electronic address:

Grafting functional polymer chains onto porous resins has been found to drastically increase both adsorption capacity and uptake rate in protein chromatography. In this work, 2-aminoethyl methacrylate (AEM) was used for grafting onto Sepharose FF gel, and six anion-exchangers of different polyAEM (pAEM) chain lengths (ionic capacities, ICs), FF-pAEM, were obtained for protein adsorption and chromatography. It was found that protein adsorption capacity (q) increased with increasing pAEM chain length, but the uptake rate, represented by the ratio of effective pore diffusivity to the free solution diffusivity (D/D), showed an up-down trend, reaching a peak value (D/D=0.55) at an IC of 313 mmol/L. Partial charge neutralization of the AEM-grafted resin of the highest IC (513 mmol/L) by reaction with sodium acetate produced three charge-reduced resins, FF-pAEM513-R. With reducing the charge density, the adsorption capacity kept unchanged and then decreased, but the uptake rate monotonically increased, reaching a maximum (about 2-fold increase) at a residual IC of 263 mmol/L. It is notable that, at the same IC, the charge-reduced resin (FF-pAEM513-R) presented similar or even higher values of q and D/D than its FF-pAEM counterpart. Particularly, at the same IC of 263 mmol/L, a ~50% enhancement of D/D was observed. Both adsorption capacity and uptake rate in the charge-reduced resin with a residual IC of 339 mmo/L (FF-pAEM513-R339) decreased more sharply with increasing NaCl concentration by comparison with FF-pAEM513, indicating its increased salt-sensitivity than FF-pAEM513. That is, charge reduction on the AEM-grafted resin could accelerate protein uptake at 0 mmol/L NaCl but decrease salt tolerance. Column breakthrough experiments showed that FF-pAEM513-R339 was favorable for high flow rate protein chromatography at low NaCl concentration (0 mmol/L), whereas FF-pAEM513 was a good choice in a wide range of salt concentrations at low flow rate. This research proved the excellent protein chromatography performance of the AEM-based anion-exchangers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2020.461869DOI Listing
February 2021

Associations of urinary carbon disulfide metabolite with oxidative stress, plasma glucose and risk of diabetes among urban adults in China.

Environ Pollut 2021 Mar 29;272:115959. Epub 2020 Oct 29.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, And State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address:

Carbon disulfide (CS) has been reported to induce disorder of glucose metabolism. However, the associations of CS exposure with plasma glucose levels and risk of diabetes have not been explored in general population, and the underlying mechanisms remain unclear. We aim to examine the relationships between CS exposure and fasting plasma glucose (FPG) levels, as well as diabetes, and assess the potential role of oxidative stress among the abovementioned relationships in Chinese general adults. The concentrations of urinary biomarkers of CS exposure (2-thiothiazolidin-4-carboxylic acid, TTCA), and biomarkers for lipid peroxidation (8-isoprostane, 8-iso-PGF) and DNA oxidative damage (8-oxo-7,8-dihydro-20-deoxyguanosine, 8-OHdG) were measured among 3338 urban adults from the Wuhan-Zhuhai cohort. Additionally, FPG levels were tested promptly. Generalized linear models and logistic regression models were used to quantify the associations among urinary TTCA, oxidative damage markers, FPG levels and diabetes risk. Mediation analysis was employed to estimate the role of oxidative damage markers in the association between urinary TTCA and FPG levels. We discovered a significant relationship between urinary TTCA and FPG levels with regression coefficient of 0.080 (95% CI: 0.002,0.157). Besides, the risk of diabetes was positively related to urinary TTCA (OR:1.282, 95% CI: 1.055,1.558), particularly among those who did not exercise regularly. Each 1% increase of urinary TTCA concentration was associated with a 0.096% and 0.037% increase in urinary 8-iso-PGF and 8-OHdG, respectively. Moreover, we found an upward trend of FPG level as urinary 8-iso-PGF gradually increased (P<0.05), and urinary 8-iso-PGF mediated 21.12% of the urinary TTCA-associated FPG increment. Our findings indicated that urinary CS metabolite was associated with increased FPG levels and diabetes risk in general population. Lipid peroxidation partly mediated the association of urinary CS metabolite with FPG levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2020.115959DOI Listing
March 2021

Toxicity in hematopoietic stem cells from bone marrow and peripheral blood in mice after benzene exposure: Single-cell transcriptome sequencing analysis.

Ecotoxicol Environ Saf 2021 Jan 26;207:111490. Epub 2020 Oct 26.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China. Electronic address:

Benzene is a ubiquitous, occupational, and environmental hematotoxic and leukemogen. Damage to hematopoietic stem cells (HSCs) induced by benzene and its metabolites is a key event in bone marrow (BM) depression and leukemogenesis. There are no reports on transcriptome profiles of HSCs following benzene exposure. Here, Smart-seq2 single-cell transcriptome sequencing was used to detect transcriptomic alternations in BM HSCs and peripheral blood HSCs (PBSCs) in male C57B/6 mice exposed to benzene. We found that benzene caused hematotoxicity which was confirmed by routine blood test, pathological examination, and HSCs percentage analysis. A total of 1514 differentially expressed genes (DEGs) in BM HSCs and 1703 DEGs in PBSCs were screened after treatment with benzene. Weighted gene correlation network analysis revealed that pathways in cancer, transcriptional misregulation in cancer, and hematopoietic cell lineage are vital pathways involved in benzene-induced toxicity in BM HSCs, whereas hematopoietic cell lineage and leukocyte transendothelial migration are critical pathways in PBSCs. Of note, there were 164 common DEGs in both HSCs, out of which 53 genes were co-regulated in both types of HSCs. Subsequent pathway analysis of these 53 genes indicated that the most relevant pathways involved neutrophil degranulation and CD93 localized in the core of the network of the 53 genes, which are known to regulate leukemia stem cell self-renewal and quiescence. Our results could enhance our understanding of HSC responses to benzene, facilitate the identification of potential molecular biomarkers and future studies on its mechanism of toxicity toward HSCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2020.111490DOI Listing
January 2021

Epidemiological characteristics and the entire evolution of coronavirus disease 2019 in Wuhan, China.

Respir Res 2020 Oct 8;21(1):257. Epub 2020 Oct 8.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.

Background: Coronavirus Disease 2019 (COVID-19) spread rapidly around the world. We aimed to describe the epidemiological characteristics and the entire evolution of COVID-19 in Wuhan, and to evaluate the effect of non-pharmaceutical intervention by the government.

Methods: The information of COVID-19 cases until Mar 18, 2020 in Wuhan were collected from the national infectious disease surveillance system in Hubei province.

Results: A total of 49,973 confirmed cases were reported until Mar 18, 2020 in Wuhan. Among whom, 2496 cases died and the overall mortality was 5.0%. Most confirmed cases (25,619, 51.3%) occurred during Jan 23 to Feb 4, with a spike on Feb 1 (new cases, 3374). The number of daily new cases started to decrease steadily on Feb 19 (new cases, 301) and decreased greatly on Mar 1 (new cases, 57). However, the mortality and the proportion of severe and critical cases has been decreasing over time, with the lowest of 2.0 and 10.1% during Feb 16 to Mar 18, 2020, respectively. The percentage of severe and critical cases among all cases was 19.6%, and the percentage of critical and dead cases aged over 60 was 70.1 and 82.0%, respectively.

Conclusion: The number of new cases has dropped significantly after the government taking the isolation of four types of personnel and the community containment for 14 days. Our results indicate that the mortality and proportion of severe and critical cases gradually decreased over time, and critical and dead cases are more incline to be older individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-020-01525-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542568PMC
October 2020

Protein adsorption to (3-acrylamido propyl) trimethyl ammonium chloride-grafted Sepharose gel: Charge density reduction via copolymerizing with electroneutral monomer drastically increases uptake rate.

J Chromatogr A 2020 Oct 18;1629:461483. Epub 2020 Aug 18.

Department of Biochemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China; Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China. Electronic address:

Polymer-grafting to porous materials is an effective way to create protein ion-exchangers of high capacity and uptake rate because the 3D architecture of the polymeric ion exchange groups provides high binding space and facilitated transport of the bound protein. Herein, a new anion exchanger was fabricated by grafting (3-acrylamide propyl) trimethyl ammonium chloride (APTAC) onto Sepharose FF gel for protein adsorption and chromatography. The ion exchanger, denoted as FF-pAPTAC, presented high capacity but limited uptake rate in bovine serum albumin (BSA) adsorption due to the high charge density of the cationic polymer chains. To solve the problem, we proposed to copolymerize APTAC with an electroneutral monomer, acrylamide (AM), onto Sepharose FF to modulate the charge density of the grafted polymer chains. By decreasing the feeding molar ratio of APTAC to AM, the ionic capacity (IC) of the copolymerized resins, FF-p(AM-APTAC)n (n denotes IC in mmol/L), decreased, but the chain length could be remained almost unchanged due to the similar reactivity ratios of the two monomers. With decreasing IC, the static adsorption capacity (q) of FF-p(AM-APTAC)n decreased gradually because of the decline of protein binding sites. The uptake rate, however, represented by the ratio of effective pore diffusivity to the free solution diffusivity (D/D), exhibited a strong uptrend with decreasing IC, reaching ~2.5-fold of the maximum observed with FF-pAPTACn. It is considered that the decrease of charge density weakened protein binding strength to the chains and increased the chain flexibility, which consequently facilitated the transport of bound proteins on the chains. Moreover, at the same IC, each FF-p(AM-APTAC)n displayed similar adsorption capacity but high uptake rate as compared with its FF-pAPTACn counterpart mainly due to the longer chain length of the copolymer. Particularly, ~6.5-fold enhancement of D/D was observed at IC = 50 ± 2 mmol/L. Both high adsorption capacity and uptake rate made FF-p(AM-APTAC)n exhibit superior dynamic binding performance. The findings proved that reducing chain charge density by copolymerizing an electroneutral monomer was promising for fabrication of high-performance protein ion exchangers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2020.461483DOI Listing
October 2020

l-Carnitine protects against 1,4-benzoquinone-induced apoptosis and DNA damage by suppressing oxidative stress and promoting fatty acid oxidation in K562 cells.

Environ Toxicol 2020 Oct 1;35(10):1033-1042. Epub 2020 Jun 1.

Key Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing, China.

Widespread occupational and environmental exposure to benzene is unavoidable and poses a public health threat. Studies of potential interventions to prevent or relieve benzene toxicity are, thus, essential. Research has shown l-carnitine (LC) has beneficial effects against various pathological processes and diseases. LC possesses antioxidant activities and participates in fatty acid oxidation (FAO). In this study, we investigated whether 1,4-benzoquinone (1,4-BQ) affects LC levels and the FAO pathway, as well as analyzed the influence of LC on the cytotoxic effects of 1,4-BQ. We found that 1,4-BQ significantly decreased LC levels and downregulated Cpt1a, Cpt2, Crat, Hadha, Acaa2, and Acadvl mRNA expression in K562 cells. Subsequent assays confirmed that 1,4-BQ decreased cell viability and increased apoptosis and caspase-3, -8, and -9 activities. It also induced obvious oxidative stress and DNA damage, including an increase in the levels of reactive oxygen species and malondialdehyde, tail DNA%, and olive tail moment. Additionally, the mitochondrial membrane potential was significantly reduced. Cotreatment with LC (500 μmol/L) relieved these alterations by reducing oxidative stress and increasing the protein expression levels of Cpt1a and Hadha, particularly in the 20 μmol/L 1,4-BQ group. Thus, our results demonstrate that 1,4-BQ causes cytotoxicity, reduces LC levels, and downregulates the FAO genes. In contrast, LC exhibits protective effects against 1,4-BQ-induced apoptosis and DNA damage by decreasing oxidative stress and promoting the FAO pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/tox.22939DOI Listing
October 2020

Increasing incidence of asbestosis worldwide, 1990-2017: results from the Global Burden of Disease study 2017.

Thorax 2020 09 28;75(9):798-800. Epub 2020 May 28.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

Global incidence and temporal trends of asbestosis are rarely explored. Using the detailed information on asbestosis from the Global Burden of Disease (GBD) 2017, we described the age-standardised incidence rate (ASIR) and its average annual percentage change. A Joinpoint Regression model was applied to identify varying temporal trends over time. Although the use of asbestos has been completely banned in many countries, the ASIR of asbestosis increased globally from 1990 to 2017. Furthermore, the most pronounced increases in ASIR of asbestosis were detected in high-income North America and Australasia. These findings indicate that efforts to change the asbestos regulation policy are urgently needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2020-214822DOI Listing
September 2020

Triiodothyronine Attenuates Silica-Induced Oxidative Stress, Inflammation, and Apoptosis via Thyroid Hormone Receptor α in Differentiated THP-1 Macrophages.

Chem Res Toxicol 2020 05 3;33(5):1256-1265. Epub 2020 Apr 3.

Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Alveolar macrophage (AM) injury and inflammatory response are key processes in pathological damage caused by silica. However, the role of triiodothyronine (T3) in silica-induced AM oxidative stress, inflammation, and mitochondrial apoptosis remained unknown. To investigate the possible effects and underlying mechanism of T3 in silica-induced macrophage damage, differentiated human acute monocytic leukemia cells (THP-1) were exposed to different silica concentrations (0, 50, 100, 200, and 400 μg/mL) for 24 h. Additionally, silica-activated THP-1 macrophages were treated with gradient-dose T3 (0, 5, 10, 20, and 40 nM) for 24 h. To illuminate the potential mechanism, we used short hairpin RNA to knock down the thyroid hormone receptor α (TRα) in the differentiated THP-1 macrophages. The results showed that T3 decreased lactate dehydrogenase and reactive oxygen species levels, while increasing cell viability and superoxide dismutase in silica-induced THP-1 macrophages. In addition, silica increased the expression of interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), and T3 treatment reduced those pro-inflammatory cytokines secretion. Compared with silica-alone treated groups, cells treated with silica and T3 restored the mitochondrial membrane potential loss and had reduced levels of cytochrome and cleaved caspase-3 expressions. Lastly, we observed that TRα-knockdown inhibited the protective effects of T3 silica-induced THP-1 macrophages. Together, these findings revealed that T3 could serve as a potential therapeutic target for protection against silica-induced oxidative stress, inflammatory response, and mitochondrial apoptosis, which are mediated by the activation of the T3/TRα signal pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.chemrestox.0c00018DOI Listing
May 2020

Association between indoor formaldehyde exposure and asthma: A systematic review and meta-analysis of observational studies.

Indoor Air 2020 07 19;30(4):682-690. Epub 2020 Mar 19.

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

About 339 million people worldwide are suffering from asthma. We aimed to investigate whether exposure to formaldehyde (FA) is associated with asthma, which could provide clues for preventive and mitigation actions. This article provides a systematic review and meta-analysis of observational studies to assess the association between indoor FA exposure and the risk of asthma in children and adults. An electronic search of PubMed, Embase, and Web of Science was performed to collect all relevant studies published before January 1, 2020, and a total of 13 papers were included in this meta-analysis. A random-effect model was conducted to calculate the pooled odds ratio (OR) between FA exposure and asthma. We found that each 10 µg/m increase in FA exposure was significantly associated with a 10% increase in the risk of asthma in children (OR = 1.10, 95% confidence interval = 1.00-1.21). We sorted the FA concentrations reported in the selected articles and categorized exposure variables into low (FA ≤ 22.5 µg/m ) and high exposure (FA > 22.5 µg/m ) according to the median concentration of FA. In the high-exposure adult group, FA exposure may also be associated with an increased risk of asthma (OR = 1.81, 95% CI = 1.18-2.78).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ina.12657DOI Listing
July 2020

Protein adsorption to poly(ethylenimine)-modified Sepharose FF: VIII: Impacts of surface ion-exchange groups at different polymer grafting densities.

J Chromatogr A 2020 Jan 10;1610:460538. Epub 2019 Sep 10.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Our previous studies on protein adsorption to the anion-exchangers of poly(ethylenimine) (PEI)-grafted Sepharose FF found that both adsorption capacity and uptake rate of bovine serum albumin (BSA) increased greatly when the PEI grafting density reached over a critical ionic capacity (cIC) due to the 3D protein binding and occurrence of "chain delivery" of bound proteins. Moreover, by the investigation on the anion-exchangers of diethylaminoethyl (DEAE)-modified and DEAE-dextran-grafted Sepharose FF, we found the unique role of surface ligand in facilitating protein uptake kinetics on dextran-functionalized anion exchangers as the "transfer station" for the "chain delivery" of bound proteins. However, what would be the contribution of surface ligands on the transport of bound proteins on PEI chains at a wide range across cIC, particularly at the lower IC range where no "chain delivery" was present? We have thus designed this research to answer the question. To this purpose, we fabricated three series of PEI-Sepharose FF resins, one without surface ligand (i.e., FF-PEI) and two with surface DEAE modifications at DEAE coupling densities of 60 and 90 mmol/L (i.e., FF-D60-PEI and FF-D90-PEI), and focused on the role of surface DEAE at different PEI densities in BSA adsorption equilibrium and uptake kinetics in a wide IC range of PEI across cIC (∼600 mmol/L for BSA). It was found that, at low grafting-ligand densities (IC cIC, however, both adsorption capacity and uptake rate changed only slightly (<5% and <10%, respectively) by the addition of surface DEAE groups. The results revealed that at IC < cIC, the surface DEAE groups provided the supplement of available binding sites and facilitated the happenings of the "chain delivery" of bound proteins as the "transfer station", both of which were limited at the low IC range. However, at IC > cIC, the extended flexible PEI chains have already afforded 3D binding space with high accessibility and easy happening of "chain delivery" of bound proteins, so the surface DEAE groups between neighboring PEI chains did not work in assisting the transport of bound proteins. Moreover, when the IC was lower but close to the cIC, the FF-D-PEI resins exhibited higher uptake rates than FF-PEI resins at a similar or even lower IC values. These findings indicate that surface modification of charged groups in PEI-based anion exchangers of low grafting density would be an efficient strategy to fabricate high performance protein ion exchangers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2019.460538DOI Listing
January 2020

Protein adsorption to poly(ethylenimine)-modified sepharose FF: VII. Complicated effects of pH.

J Chromatogr A 2018 Dec 22;1580:72-79. Epub 2018 Oct 22.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Previously, we have studied protein adsorption behaviors on a series of poly(ethylenimine) (PEI)-grafted Sepharose FF, and a critical ionic capacity of PEI-grafted resins was observed, above which both protein adsorption capacity (q) and effective pore diffusivity (D) increased drastically. Moreover, reducing the charge density of the PEI-grafted resins from an ionic capacity of 740 mmol/L (FF-PEI-L740) to 440 mmol/L (FF-PEI-R440) by neutralization of the amino groups of PEI chains with sodium acetate brought out a three-fold increase of D value at pH 8. In this work, FF-PEI-L740 and FF-PEI-R440 were selected to investigate the complicated effects of pH on protein adsorption behavior using bovine serum albumin (BSA) as the model protein. It was found that, for FF-PEI-L740, both the q and D values decreased significantly when pH decreased from 9 to 5.5, and then increased dramatically at pH 5, and finally decreased remarkably at pH 4.5. The results were considered due to the following causes: The decrease of pH from 9 to 5.5 led to a greatly increased electrostatic repulsion between the PEI chains due to the increased dissociation degree of PEI, which caused the increase in steric hindrance effects and decrease in the bound protein transport by chain delivery. At pH 5, which was near the pI of BSA (∼4.9), the presence of few protein charges greatly decreased the electrostatic hindrance effect on protein transport and the high charge density of FF-PEI-L740 provided extensively accessible binding sites and facilitated the happening of chain delivery as well. At pH 4.5, the net charge of BSA shifted to positive, likely charged with PEI, so the overall electrostatic repulsion greatly hindered protein uptake. For FF-PEI-R440, whose charge density was much lower than FF-PEI-L740, its q and D values even increased mildly when pH decreased from 8 to 5.5, because its slightly-increased charge density did not cause much increased electrostatic and steric hindrance effects but provided more binding sites for protein adsorption. At pH 5, the few charges of BSA and the low charge density of FF-PEI-R440 could not afford enough electrostatic interaction for protein binding, resulting in significantly decreased q and D values. Besides, column breakthrough experiments revealed that FF-PEI-R440 kept high dynamic binding capacity (DBC) (>120 mg/mL) at pH 5.5-8, while FF-PEI-L740 offered high DBC (>80 mg/mL) at pH 5, 7 and 8 with a higher salt concentration (100 mmol/L NaCl). These findings demonstrated the excellence of FF-PEI-L740 and FF-PEI-R440 in different conditions, and would help in the design and selection of suitable resins for high-performance protein chromatography.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2018.10.033DOI Listing
December 2018

Characterization of new polymer-grafted protein cation exchangers developed by partial neutralization of carboxyl groups derivatized by modification of poly(ethylenimine)-Sepharose with succinic anhydride.

J Chromatogr A 2018 May 23;1550:28-34. Epub 2018 Mar 23.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Previously, we have studied protein adsorption and chromatographic behaviors on poly(ethylenimine) (PEI)-grafted Sepharose FF anion-exchange resins, and found that protein uptake rates increased greatly when PEI grafting density reached over a critical ionic capacity (cIC) due to the occurrence of the "chain delivery" effect. Moreover, by partial charge neutralization of starting resin FF-PEI-L740 (IC = 740 mmol/L, larger than the cIC) with sodium acetate to FF-PEI-R440, it exhibited a three-fold increase in uptake rate over FF-PEI-L740. In this work, to take the advantages of PEI and extend the applications of the PEI-grafted resins in cation-exchange chromatography, a series of cation exchangers of five different ICs were developed. First, the charged of FF-PEI-L740 was reversed from positive to negative by reaction with excess succinic anhydride, which created a cation-exchanger with an IC of 970 mmol/L (FF-FEI-C970). FF-PEI-C970 was further modified with ethanolamine for partial charge neutralizations, leading to the preparation of four charge-reduced cation exchangers with IC values (in mmol/L) of 780, 630, 560 and 430, which were denoted as FF-PEI-CR780, -CR630 -CR560 and -CR430, respectively. Protein adsorption and chromatographic behaviors were investigated using lysozyme (Lys) as the model protein. It was found that, the resins of high and moderate IC values (IC ≥ 560 mmol/L) afforded adsorption capacities up to over 230 mg/mL. Besides, the uptake rate, represented by the effective pore diffusivity (DD), exhibited significant increase from 0.067 (FF-PEI-C970 and FF-PEI-CR780) to 0.343 (FF-PEI-CR630 and FF-PEI-CR560) and then to 1.035 (FF-PEI-CR430) with decreasing IC. It was considered that decreasing IC led to the decreased protein binding sites (binding strength), which encouraged the occurrence of the "chain delivery" effect. Moreover, the resins of high and moderate IC values, particularly, the resins of moderate IC values (FF-PEI-CR630 and FF-PEI-CR560), presented both high adsorption capacities and uptake kinetics at 0-100 mmol/L NaCl. Besides, dynamic binding capacity achieved 150 mg/mL for the resins of moderate IC values at 0 mmol/L NaCl concentration, and afforded >110 mg/mL for the resin of high IC values at 0-100 mmol/L NaCl concentration. The results proved the excellent IEC performance of the PEI-derived cation exchangers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2018.03.046DOI Listing
May 2018

Kinetic Insights into Zn-Induced Amyloid β-Protein Aggregation Revealed by Stopped-Flow Fluorescence Spectroscopy.

J Phys Chem B 2017 04 18;121(16):3909-3917. Epub 2017 Apr 18.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University , Tianjin 300072, China.

Zn has remarkable impacts on amyloid β-protein (Aβ) aggregation, which is crucial in the pathology of Alzheimer's disease. However, the Zn concentration in human cerebrospinal fluid is commonly too low for interaction with Aβ, and only during neurotransmission is there a transient release of a high concentration of Zn. It is difficult to explore the details of the interaction between Zn and Aβ within such a short time scale by using ordinary analytical methods. Herein, stopped-flow fluorescence spectroscopy was used to study the fast aggregation kinetics of Aβ in the presence of Zn in the time scale from 1 ms to seconds. It was found that Zn bound to Aβ within 1 ms; caused immediate conformational transition around Tyr10, which led to the enhancement of Aβ hydrophobicity; and then promoted fast aggregation of Aβ through enhanced hydrophobic interactions. Among the two Zn-binding sites on Aβ (K = 107 nM and 5.2 μM), the first one of higher affinity had a greater impact on the aggregation of Aβ. Three kinetic phases were observed in the Zn-induced fast aggregation of Aβ, and the fast phase was extremely accelerated by Zn, indicating that accelerated aggregation mainly occurred in the fast phase. The reactions occurring in this phase were closely related to the association of Zn and Aβ. Moreover, Zn largely broadened the pH range of Aβ fast aggregation from pH 5.2-6.2 without Zn to pH 5.2-7.8 in the presence of Zn. Besides, the promoting effect of Zn on Aβ fast aggregation peaked at pH 6.8-7.8, which includes the pH values of the cerebrospinal fluid (pH 7.3) and hippocampus (pH 7.15-7.35). The findings demonstrate the significant effect of Zn on Aβ aggregation and provide new insight into its mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpcb.6b12187DOI Listing
April 2017

Synergistic effects of negatively charged hydrophobic nanoparticles and (-)-epigallocatechin-3-gallate on inhibiting amyloid β-protein aggregation.

J Colloid Interface Sci 2017 Apr 19;491:305-312. Epub 2016 Dec 19.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Fibrillogenesis of amyloid β-protein (Aβ) in human brain has been implicated as the main cause of Alzheimer's disease. A few small molecules from natural sources have been discovered for their inhibition effects on Aβ fibrillation, of which (-)-epigallocatechin-3-gallate (EGCG) is one of the most broadly investigated compounds for its potent inhibitory activity. However, in vivo applicability of the inhibitors is largely limited by their low transmembrane efficiency. Hence, it is of great significance to develop inhibition systems that function at low concentrations. In this work, a dual-inhibitor system containing EGCG and negatively charged polymeric nanoparticles (NP10), which was also demonstrated effective on the inhibition of Aβ aggregation, was developed and comprehensively studied by extensive biophysical and biological assays. It was found that the dual-inhibitor system at low concentrations was more effective on the inhibition and detoxification of Aβ (Aβ and Aβ) fibrillation than the additive effects of these two agents working individually. Namely, there was a synergistic effect of the two inhibitors. The synergism factor reached 1.25 with 5μM EGCG and 5μg/mL NP10. Kinetic studies with Aβ revealed that the two inhibitors functioned in different Aβ assembling stages: NP10 mainly inhibited primary nucleation, while EGCG suppressed fibril elongation and changed the fibril structure to make it show less seeding activities in the secondary nucleation. NP10 might also help EGCG binding to Aβ, leading to its enhanced inhibitory effects on fibril elongation and secondary nucleation. The synergistic effect observed in the dual-inhibitor system offered new insight into the development of potent inhibitor systems against amyloid neurotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2016.12.038DOI Listing
April 2017

Characterization of poly(allylamine) as a polymeric ligand for ion-exchange protein chromatography.

J Chromatogr A 2017 Feb 10;1486:103-109. Epub 2016 Nov 10.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

This work reports poly(allylamine) (PAA), as a polymeric ion-exchange ligand for protein chromatography. Sepharose FF was modified with PAA, and six anion exchangers with ionic capacities (ICs) from 165 to 618mmol/L were prepared. Inverse size exclusion chromatography, adsorption equilibrium, uptake kinetics and column elution were performed. It was found that both the adsorption capacity and effective diffusivity maintained low values in the IC range of 165-373mmol/L, but they started to increase beyond 373mmol/L, and increased by 80% and 23 times, respectively, when the IC reached 618mmol/L. Interestingly, a drastic decrease of pore size was observed around the IC of 373mmol/L. The results suggest that the PAA chains played an important role in protein adsorption by altering the inner pore structure of the gels. It is considered that, PAA chains turn from inextensible states with multipoint-grafting on the pore surface at low coupling densities (IC<373mmol/L) to closer, extended and flexible grafting states with less coupling points at higher coupling densities (IC>373mmol/L). These characters of the grafted chains at higher IC values benefit in protein adsorption by three-dimensional binding and encouraged the happening of "chain delivery" of bound proteins on the chains. Besides, the ion exchangers showed favorable adsorption and uptake properties in a wide ionic strength range, 0-500mmol/L NaCl, indicating much better salt tolerance feature than the so-far reported ion exchangers. Moreover, a mild condition of pH 5.0 offered effective recovery of bound proteins in elution chromatography. The results indicate that the PAA-based anion exchanger of a high IC value is promising for high-capacity protein chromatography dealing with feedstock of a wide range of ionic strengths.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2016.11.012DOI Listing
February 2017

Grafting glycidyl methacrylate to Sepharose gel for fabricating high-capacity protein anion exchangers.

J Chromatogr A 2016 Apr 16;1443:118-25. Epub 2016 Mar 16.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

To develop ion exchangers of high protein adsorption capacity, we have herein introduced atom transfer radical polymerization (ATRP) method to graft glycidyl methacrylate (GMA) onto Sepharose FF gel. GMA-grafted Sepharose FF resins of four grafting densities and different grafting chain lengths were obtained by adjusting reaction conditions. The epoxy groups on the grafted chains were functionalized by modification with diethylamine (DEA), leading to the fabrication of Sepharose-based anion exchangers of 14 different grafting densities and/or grafting chain lengths. The resins were first characterized for the effects of grafting density, chain length and ionic strength on pore sizes by inverse size exclusion chromatography. Then, the resins were evaluated by adsorption equilibria of bovine serum albumin (BSA) as a function of ionic capacity (IC) (chain length) at individual grafting densities. It was observed that at each grafting density there was a specific IC value (chain length) that offered the maximum equilibrium capacity. Of the resins with maximum values at individual grafting densities, the resin of the second grafting density with an IC value of 330 mmol/L (denoted as FF-Br2-pG-D330) showed the highest capacity, 264 mg/mL, about two times higher than that of the traditional ungrafted resin Q Sepharose FF (137 mg/mL). This resin also showed the most favorable uptake kinetics among the resins of similar IC values but different grafting densities, or of the same grafting density but different IC values. Effects of ionic strength showed that the capacities of FF-Br2-pG-D330 were much higher than Q Sepharose FF at a wide range of NaCl concentrations (0-200 mmol/L), and the uptake rates of the two resins were similar in the ionic strength range. Therefore, the dynamic binding capacity values of BSA on FF-Br2-pG-D330 were much higher than Q Sepharose FF as demonstrated at different residence times and ionic strengths. Taken together, the research has proved the success in the fabrication of high-capacity protein anion exchangers by grafting GMA onto Sepharose gel.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2016.03.033DOI Listing
April 2016

Protein adsorption to poly(ethylenimine)-modified Sepharose FF: VI. Partial charge neutralization drastically increases uptake rate.

J Chromatogr A 2016 Jan 2;1427:102-10. Epub 2015 Dec 2.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

The adsorption and elution behaviors of bovine serum albumin (BSA) on poly(ethylenimine) (PEI)-grafted Sepharose FF resins were recently studied and a critical ionic capacity (cIC; 600 mmol/L) was found, above which the uptake rate increased drastically due to the occurrence of significant "chain delivery" effect. Moreover, above the cIC value, higher salt concentrations were required for protein elution due to the high charge density of the resins. In this work, we have reduced the charge density on the PEI chains of a PEI-grafted resin by neutralization of the amine groups with sodium acetate. PEI-modified resin with IC of 740 mmol/L (FF-PEI-L740, IC>cIC) was chosen as the starting material, and three resins with residual IC values of 660, 560 and 440 mmol/L (FF-PEI-R440) were obtained. The adsorption and chromatographic behaviors of these resins for BSA were investigated. It was found that, with IC decreasing from 740 to 440 mmol/L, the adsorption capacity kept almost unchanged; the effective protein diffusivity (De) also showed negligible variations as IC decreased from 740 to 560 mmol/L (De/D0=0.38 ± 0.04). However, it was interesting to observe a three-fold increase of the De value for FF-PEI-R440 (De/D0=1.23 ± 0.08). It is considered that the occurrence of the drastic uptake rate increase in FF-PEI-R440 was attributed to the decreased available binding sites for protein molecule, which led to the decrease of binding strength, thus facilitated the happenings of "chain delivery" effect of bound proteins. Besides, a study on the effect of ionic strength clarified that the lower the IC value, the higher the sensitivity of protein binding to salt concentration due to the easily screened electrostatic interactions at low surface charge densities. The ionic strength at the elution peak also decreased with decreasing IC in accordance with the salt sensitivity order. Column breakthrough studies demonstrated that the dynamic adsorption capacity of FF-PEI-R440 was much higher than the other three resins at flow rates higher than 30 cm/h because of its high uptake rate. The findings in this work provided new insights into the effects of the interactions between proteins and grafted polymers on adsorption equilibria and uptake kinetics, which would help the selection and design of suitable media for high-performance protein chromatography.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2015.11.084DOI Listing
January 2016

Protein adsorption to poly(ethylenimine)-modified Sepharose FF: V. Complicated effects of counterions.

J Chromatogr A 2015 Jul 28;1404:44-50. Epub 2015 May 28.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

In the previous studies on protein adsorption to poly(ethylenimine) (PEI)-grafted Sepharose FF resins, a critical ionic capacity (600mmol/L) of PEI-Sepharose resins was found for the adsorption of bovine serum albumin (BSA), above which both protein capacity and uptake rate increased drastically. In this work, the influence of counterions on the PEI-Sepharose resin with an ionic capacity of 683mmol/L (FF-PEI-L680) was investigated with sodium salts of SCN(-), Cl(-), HPO4(2-) and SO4(2-). Linear gradient elution, batch adsorption and breakthrough experiments showed that counterion preference, effective pore diffusion coefficient (De) and dynamic binding capacity (DBC) values increased in the order of SCN(-), Cl(-), HPO4(2-) and SO4(2-), while static adsorption capacity decreased in this order. It is considered that higher counterion preference of the ion exchange groups resulted in lower protein binding strength and adsorption capacity, while the De value increased due to the enhanced "chain delivery" effect (a kind of surface diffusion). Besides, the DBC value was mainly dependent on De value. In particular, SO4(2-) was the most favorable counterion for the PEI-Sepharose resin, which gave rise to the highest De value (De/D0=1.17, D0 is protein diffusivity in free solution) and DBC value (118mg/mL at a residence time of 2min). Moreover, the effects of counterions on BSA adsorption to DEAE Sepharose FF and Q Sepharose FF, which were non-grafted resins, were also studied for comparisons. It was found that the counterion preferences of the two non-grafted resins were different from each other and also different from that of FF-PEI-L680. The different counterion preferences were attributed to the differences in the ion-exchange ligand chemistries. In addition, the De values for DEAE Sepharose FF and Q Sepharose FF kept unchanged. The low counterion sensitivity of De values could be interpreted as the lack of "chain delivery" effect for the non-grafted resins. The results indicate that protein adsorption and chromatographic performance with PEI-Sepharose can be improved by proper counterions. For the four counterions tested, SO4(2-) was the most favorable for providing the best adsorption and elution outcomes with FF-PEI-L680.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2015.05.046DOI Listing
July 2015

Protein behavior at surfaces: orientation, conformational transitions and transport.

J Chromatogr A 2015 Feb 9;1382:118-34. Epub 2015 Jan 9.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Chromatography is the key technology in protein purification as well as in protein refolding. Taking the scientific development and technological innovation of protein chromatography as the objective, this article is devoted to an overview of protein behavior at chromatographic surfaces, including protein orientation, conformational transitions (unfolding and refolding), and protein transport. Recent advances achieved by using molecular simulations as well as theoretical and experimental investigations are elaborated and discussed with emphasis on their implications to the rational design of novel chromatographic surfaces or materials and mobile phase conditions for the development of high-performance protein chromatography.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2014.12.087DOI Listing
February 2015

Characterization of novel mixed-mode protein adsorbents fabricated from benzoyl-modified polyethyleneimine-grafted Sepharose.

J Chromatogr A 2014 12 8;1372C:157-165. Epub 2014 Nov 8.

Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China. Electronic address:

We have previously studied poly(ethylenimine) (PEI)-grafted Sepharose FF resins for ion-exchange chromatography of bovine serum albumin (BSA), and found the presence of a critical ionic capacity (cIC, 600mmol/L for BSA), above which both BSA adsorption capacity and uptake rates increased drastically. To extend the application of PEI-grafted resins, we have herein proposed to develop mixed-mode chromatographic (MMC) resins by modifying the grafted PEI chains with hydrophobic benzoyl groups. Three PEI-grafted resins with IC values from 329 to 701mmol/L (FF-PEI-L330, FF-PEI-L520 and FF-PEI-L700) were modified with benzoic acid. It was found that there was a maximum benzoyl density (BD) that could be reached for each resin, at which the average value of BD/residual IC was 1.2. The effect of BD (120-400mmol/L) on BSA adsorption (at pH 8.0) and elution (at pH 3.0) was first explored with FF-PEI-L700-derived resins. It was observed that both protein binding capacity and recovery increased with increasing BD, indicating that high BD was beneficial in protein adsorption. However, the elution of bound BSA with an acidic buffer (pH 3.0) was incomplete. It was hypothesized that the PEI chains, a pH-dependent cationic polyelectrolyte, formed a collapsed layer at the protein binding condition (high ionic strength, IS), while they exhibited extended spatial structures at elution (low pH and IS). These PEI chain structure transitions made the pores change from an opening state at the loading condition to a blocked state at the elution condition. The pore blocking was regarded as a chain-aroused-steric-hindrance (CaSH) effect. Thus, FF-PEI-L700 was not suitable for fabricating MMC resins due to its high chain density. Then, the effect of PEI density (the initial IC values of 330-700mmol/L) at the maximum BD values was investigated. Consequently, complete BSA recovery at pH 3.0 was obtained on the resin with an initial IC of 330mmol/L and a BD of 160mmol/L (B160-PEI330). The result indicates that the CaSH effect could be ignored at the low PEI chain density (IC=329mmol/L). Moreover, selective elution of γ-globulin could be achieved at pH 4.0 on the B160-PEI330 column, indicating the possibility of antibody purification from a mixture containing albumin by manipulating elution conditions. Finally, adsorption equilibria and uptake kinetics onto B160-PEI330 showed favorable binding properties for different proteins at a wide range of IS, indicating its usefulness as an MMC adsorbent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2014.10.108DOI Listing
December 2014