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991.
Identification of a major glucose transporter in Flavobacterium johnsoniae: Inhibition of F. johnsoniae colony spreading by glucose uptake
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Keigo Imamura Keiko Sato Yoshio Kondo Daisuke Nakane Mariko Naito Taku Fujiwara Koji Nakayama 《Microbiology and immunology》2018,62(8):507-516
992.
Advanced glycation end‐products and Porphyromonas gingivalis lipopolysaccharide increase calprotectin expression in human gingival epithelial cells
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993.
Chinese hamster ovary cell lines are good manufacturing practice-certified host cells and are widely used in the field of biotechnology to produce therapeutic antibodies. Recombinant protein productivity in cells is strongly associated with cell growth. To control cell proliferation, many approaches have previously been tested including: genetic engineering, chemical additives such as cell cycle inhibitors, and temperature shift of the culture. To be widely adopted in the biopharmaceutical industry, the culture methods should be simple, uniform and safe. To this end, we examined the use a natural compound to improve the production capacity. In this study, we focused on the antioxidants, catechin polyphenols, which are found in green tea, for cell proliferation control strategies. (–)-Epigallocatechin-3-gallate (EGCG), the major catechin that induces G0/G1 cell cycle arrest, was investigated for its effect on recombinant protein production. Adding EGCG to the cell culture media resulted in slower cellular growth and longer cell longevity, which improved the specific productivity and total yield of recombinant IgG1 in batch cultures by almost 50% for an extra 2 or 3 days of culture. A lower l-glutamine consumption rate was observed in cells cultured in EGCG-containing media, which may be suggesting that there was less stress in the culture environment. Additionally, EGCG did not affect the N-glycan quality of IgG1. Our results indicated that adding EGCG only on the first day of the culture enhanced the specific productivity and total amount of recombinant protein production in batch cultures. This approach may prove to be useful for biopharmaceutical production. 相似文献
994.
Longlong Tang Ryouta Ii Koji Tokimatsu Norihiro Itsubo 《The International Journal of Life Cycle Assessment》2018,23(12):2288-2299
Purpose
Global warming is exerting a damaging effect on human health. This damage is not only influenced by future climate conditions but also projected economic development and population growth. That being said, there are no health damage factors related to CO2 emissions which take into account future socioeconomic scenarios in life cycle impact assessment (LCIA). Thus, the purpose of the current research is to calculate human health damage factors based on the Special Report on Emission Scenarios (SRESs) developed by the Intergovernmental Panel on Climate Change (IPCC).Methods
The procedure used to calculate the SRES-based damage factors is as follows. First, a framework was developed to calculate damage factors based on multiple parameters: rise in temperature, relative risk increase, mortality rate increase, rise in number of deaths, and disability-adjusted life year (DALY) increase. Secondly, these parameters were calculated for each individual SRES based on the relationship among the parameters and CO2 emissions, GDP, and population values of each scenario. Finally, the damage factor for each SRES was calculated by multiplying all the parameters that had been calculated based on the CO2 emission, GDP, and population data in the corresponding scenarios.Results and discussion
Using this method, the human health damage factors for four SRESs (A1B, A2, B1, and B2) were calculated. The damage factors consisted of six different items: malaria, diarrhea, cardiovascular disease, malnutrition, coastal flooding, and inland flooding. The calculated results by scenario were 2.0?×?10?7, 6.2?×?10?7, 2.1?×?10?7, and 4.2?×?10?7 DALY/kg CO2, respectively. The damage caused by malnutrition is the greatest, followed by diarrhea. Regions of Southeast Asia, Africa, and the Middle East showed the highest damages due to their high damage from malnutrition and diarrhea. With regard to the differences among the four damage factors, the difference between the projected future mortality rate and DALY per death based on the future GDP per capita is greater than the difference between the increases in temperature among scenarios dependent on future CO2 emission.Conclusions
The human health damage factors related to CO2 emissions for four SRESs were estimated. As a result of differences between future socioeconomic scenarios, the largest amount of damage per CO2 emission unit was three times greater than the smallest amount. Therefore, sensitive analysis is highly recommended when seeking to compare damage caused by global warming and other impact categories.995.
Sterigmatocystin (STC) and aflatoxin B1 (AFB1) were analyzed in 246 corn samples, 126 soybean meal samples, and 861 formula feed samples from the Japanese market between April 2010 and March 2015. The detection rate, the highest concentration, and the mean concentration of STC were respectively 14%, 6.4 μg/kg, and 1.2 μg/kg for corn; 14%, 1.1 μg/kg, and 0.63 μg/kg for soybean meal; and 43%, 9.1 μg/kg, and 0.97 μg/kg for formula feed. The detection rate, the highest concentration, and the mean concentration of AFB1 were respectively 46%, 24 μg/kg, and 3.9 μg/kg for corn; 30%, 6.7 μg/kg, and 1.1 μg/kg for soybean meal; and 47%, 20 μg/kg, and 1.6 μg/kg for formula feed. A weak negative correlation between the STC and AFB1 concentrations was observed: there was a high concentration of AFB1 in samples that contained a lower concentration of STC and vice versa. Spearman’s rank correlation coefficient showed a weak negative correlation of ? 0.30 (p < 0.001, n = 128) for corn and ? 0.23 (p < 0.001, n = 575) for formula feed. In conclusion, no correlation was observed between the mean concentrations of STC contamination in formula feed (0.97 μg/kg) and in corn (1.2 μg/kg) and the blending rate (approximately 50%). The rate of STC contamination in the formula feed (43%) was higher than that in corn (14%). Therefore, it is likely that ingredients other than corn contribute to the contamination of formula feed with STC. In this study, regarding STC, problematic samples were not found. 相似文献
996.
Toshihiro Hamajima Fumie Takahashi Koji Kato Koichiro Mukoyoshi Kousei Yoshihara Susumu Yamaki Yukihito Sugano Ayako Moritomo Kaoru Yamagami Koji Yokoo Hidehiko Fukahori 《Bioorganic & medicinal chemistry》2018,26(9):2410-2419
Phosphatidylinositol-3-kinase (PI3K)δ inhibition is one of the most attractive approaches to the treatment of autoimmune diseases and leukocyte malignancies. Through the exploration of pyrazolopyridine derivatives as potential PI3Kδ inhibitors, compound 12a was identified as a potent PI3Kδ inhibitor but suffered from poor oral exposure in mice. With a modified amide linkage group, compound 15a was developed as an orally available PI3Kδ inhibitor with reduced selectivity against other PI3Ks. To improve the trade-off between selectivity and PK profile, structure–activity relationship (SAR) studies of terminal substituents on the pyrolidine ring were conducted. As a result, we developed potent PI3Kδ inhibitors with good oral availability. In particular, the representative compound 15j showed excellent selectivity for PI3Kδ over other PI3Ks with good oral exposure in mice. 相似文献
997.
Toshihiro Hamajima Fumie Takahashi Koji Kato Yukihito Sugano Susumu Yamaki Ayako Moritomo Satoshi Kubo Koji Nakamura Kaoru Yamagami Nozomu Hamakawa Koji Yokoo Hidehiko Fukahori 《Bioorganic & medicinal chemistry》2018,26(14):3917-3924
Chemical optimization of pyrazolopyridine 1, focused on cellular potency, isoform selectivity and microsomal stability, led to the discovery of the potent, selective and orally available PI3Kδ inhibitor 5d. On the basis of its desirable potency, selectivity and pharmacokinetic profiles, 5d was tested in the trinitrophenylated aminoethylcarboxymethyl-Ficoll (TNP-Ficoll)-induced antibody production model, and showed higher antibody inhibition than a 4-fold oral dose of the starting compound 1. These excellent results suggest that 5d is a potential candidate for further studies in the treatment of autoimmune diseases and leukocyte malignancies. 相似文献
998.
Makoto Hibi Koji Takahashi Junko Kako Yuuta Wakita Tomohiro Kodera Sakayu Shimizu Kenzo Yokozeki Jun Ogawa 《Bioorganic & medicinal chemistry》2018,26(7):1327-1332
A panel of microorganisms was screened for selective reduction ability towards a racemic mixture of prochiral 2-amino-3-methyl-4-ketopentanoate (rac-AMKP). Several of the microorganisms tested produced greater than 0.5 mM 4-hydroxyisoleucine (HIL) from rac-AMKP, and the stereoselectivity of HIL formation was found to depend on the taxonomic category to which the microorganism belonged. The enzymes responsible for the AMKP-reducing activity, ApAR and FsAR, were identified from two of these microorganisms, Aureobasidium pullulans NBRC 4466 and Fusarium solani TG-2, respectively. Three AMKP reducing enzymes, ApAR, FsAR, and the previously reported BtHILDH, were reacted with rac-AMKP, and each enzyme selectively produced a specific composition of HIL stereoisomers. The enzymes appeared to have different characteristics in recognition of the stereostructure of the substrate AMKP and in control of the 4-hydroxyl group configuration in the HIL product. 相似文献
999.
1000.
Keishi Yamasaki Koji Nishi Makoto Anraku Kazuaki Taguchi Toru Maruyama Masaki Otagiri 《Biochemistry and Biophysics Reports》2018
It is well known that various physiological factors such as pH, endogenous substances or post-translational modifications can affect the conformational state of human serum albumin (HSA). In a previous study, we reported that both pH- and long chain fatty acid-induced conformational changes can alter the interactive binding of ligands to the two principal binding sites of HSA, namely, site I and site II. In the present study, the effect of metal-catalyzed oxidation (MCO) caused by ascorbate/oxygen/trace metals on HSA structure and the interactive binding between dansyl-L-asparagine (DNSA; a site I ligand) and ibuprofen (a site II ligand) at pH 6.5 was investigated. MCO was accompanied by a time-dependent increase in carbonyl content in HSA, suggesting that the HSA was being oxidized. In addition, The MCO of HSA was accompanied by a change in net charge to a more negative charge and a decrease in thermal stability. SDS-PAGE patterns and α-helical contents of the oxidized HSAs were similar to those of native HSA, indicating that the HSA had not been extensively structurally modified by MCO. MCO also caused a selective decrease in ibuprofen binding. In spite of the changes in the HSA structure and ligand that bind to site II, no change in the interactive binding between DNSA and ibuprofen was observed. These data indicated that amino acid residues in site II are preferentially oxidized by MCO, whereas the spatial relationship between sites I and II (e.g. the distance between sites), the flexibility or space of each binding site are not altered. The present findings provide insights into the structural characteristics of oxidized HSA, and drug binding and drug-drug interactions on oxidized HSA. 相似文献