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21.
《药学学报(英文版)》2021,11(9):2719-2725
Insulin derivatives such as insulin detemir and insulin degludec are U.S. Food and Drug Administration (FDA)-approved long-acting insulin currently used by millions of people with diabetes. These derivatives are modified in C-terminal B29 lysine to retain insulin bioactivity. New and efficient methods for facile synthesis of insulin derivatives may lead to new discovery of therapeutic insulin. Herein, we report a new method using sortase A (SrtA)-mediated ligation for the synthesis of insulin derivatives with high efficiency and functional group tolerance in the C-terminal B chain. This new insulin molecule (Ins-SA) with an SrtA-recognizing motif can be conjugated to diverse groups with N-terminal oligoglycines to generate new insulin derivatives. We further demonstrated that a new insulin derivative synthesized by this SrtA-mediated ligation shows strong cellular and in vivo bioactivity. This enzymatic method can therefore be used for future insulin design and development. 相似文献
22.
K. Fuxe K. Andersson T. Hansson L.F. Agnati P. Eneroth J.-Å. Gustafsson 《Toxicology》1984,29(4):293-305
Subacute exposure of male rats to various concentrations (70–1000 ppm) of dichloromethane (DCM) produces a selective reduction of dopamine (DA) levels without a change of DA turnover in certain types of forebrain DA nerve terminal systems. In the low concentration (70 ppm) a selective reduction of DA turnover was observed in the medial palisade zone (MPZ) of the median eminence. This chlorinated organic solvent also produced a discrete dose-dependent increase of noradrenaline (NA) turnover within the 相似文献
23.
Luba Vasiluk Linda J Pinto Wing Shan Tsang Frank A P C Gobas Curtis Eickhoff Margo M Moore 《Food and chemical toxicology》2008,46(2):610-618
Food ingestion is the major route of exposure to many hydrophobic organic contaminants (HOCs) such as benzo[a]pyrene (BaP). It has been proposed that food-bound HOCs may become bioavailable after their mobilization by gastrointestinal fluids. The purpose of this research was to measure the uptake efficiency of [(14)C]-BaP bound to skim milk powder using an in vitro model of gastrointestinal digestion followed by sorption to human enterocytes (Caco-2 cells). Neutralization of intestinal fluids released [(14)C]-BaP into the soluble fraction. Ageing of benzo[a]pyrene onto skim milk for 6 months significantly decreased the mobilized fraction but did not affect the amount of benzo[a]pyrene taken up into Caco-2 cells. Hence, significant differences in aqueous phase concentrations may not always be reflected in significant differences in uptake. We obtained evidence that the digestion/uptake of skim milk lipids is accompanied by the diffusive uptake of BaP (the fat flush hypothesis) as trans-cellular transfer of BaP was favoured in the apical to basolateral direction. These data support the theory that non-polar substances including HOCs are preferentially transferred from the lumen into the bloodstream and provide indirect evidence that the uptake is related to the fugacity gradient created by the unidirectional uptake of dietary lipids. 相似文献
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Antitumor Activity of Dichloromethane Extract from Salvia plebeia and Induction of Apoptosis on K562 Cells 下载免费PDF全文
Objective To study the antitumor activity of extract from Salvia plebeia and investigate whether the extract induce apoptosis of K562 cells.Methods The aqueous,petroleum ether,dichloromethane(CH2Cl2),ethyl acetate,and butanol extracts were prepared from the aerial parts of S.plebeia.Taking fluorouracil as reference,the cytotoxic activities of these extracts on HeLa,A549,SGC-7901,HCT-116,K562,LoVo,DU-145,and HepG2 cells were evaluated.To clarify the apoptosis of K562 cells induced by CH2Cl2 extract,the methods of Hoechst 33258 staining,flow cytometry assay,and DNA ladder assay were investigated.Results The CH2Cl2 extract showed the most potent cytotoxic effect against K562 cells,with an IC50<15μg/mL for 3 d treatment.The characteristic apoptotic symptoms such as DNA fragmentation and chromatin condensation were also observed in the K562 cells.Conclusion The CH2Cl2 extract from S.plebeia may inhibit the cancer cell proliferation by inducing cell apoptosis. 相似文献
25.
Ahua KM Ioset JR Ioset KN Diallo D Mauël J Hostettmann K 《Journal of ethnopharmacology》2007,110(1):99-104
Sixty-four extracts issued from twenty-one plants used in the Malian traditional medicine--several of them as antiparasitic drugs--were assayed for their antileishmanial effects against both extracellular and intracellular forms of Leishmania major. Seven extracts from six different plants--Sarcocephalus latifolius, Zanthoxylum zanthoxyloides, Entada africana, Bobgunnia madagascarensis, Pseudocedrela kotschyi and Psorospermum guineense--were found to be significantly active against the intracellular form of the parasite. 相似文献
26.
醋酸烯诺孕酮微球中二氯甲烷残留的限量检查 总被引:1,自引:0,他引:1
目的建立醋酸烯诺孕酮微球中二氯甲烷残留量的测定方法。方法采用溶液直接进样法测定羟尼酮中二氯甲烷残留量。使用毛细管柱CP-MAX52CB(30M×0.32mm);以高纯氮气为载气;以FID为检测器。结果微球辅料及测定所用溶剂对二氯甲烷残留量的测定无影响;二氯甲烷在1.016-10.16μg/mL内具有良好的线性;最低检测限LOD为0.12ng。结论此方法简单、准确,灵敏度高,可用于醋酸烯诺孕酮微球二氯甲烷的残留溶剂的测定。 相似文献
27.
Jacubovich RM Landau D Bar Dayan Y Zilberberg M Goldstein L 《American journal of industrial medicine》2005,48(5):389-392
BACKGROUND: Dichloromethane poisoning affects predominantly the central nervous and the cardiovascular systems, and results from both carboxyhemoglobin formation and direct solvent-related narcosis. Exposure is frequently occupational and related to paint-stripping. Several reports have described severe adverse effects as well as fatalities. Conflicting reports regarding peripheral nerve toxicity have been found with no reports of clinical acute toxicity heretofore. METHODS: We present a case report of a patient who developed a facial nerve palsy after acute occupational exposure to Dichloromethane. The patient was part of a paint removing crew who have worked without proper protecting measures and were thus exposed to high levels of Dichoromethane. RESULTS: The patient was involved in paint stripping with Dichloromethane, and developed facial nerve palsy. Other known causes of facial palsy were excluded, and although idiopathic palsy cannot be ruled out, there were no corroborating findings. Carboxyhemoglobin levels taken after a significant delay were normal. CONCLUSION: This is the first article that describes a case of Facial Nerve Palsy related to acute dichloromethane exposure, indicating a possible peripheral neurotoxic effect of this solvent. 相似文献
28.
To toxic hazzard to the eye from dichloromethane (DCM) as liquid or vapour has been assessed using rabbits. 0.1 ml DCM caused inflammation of the conjunctiva and eyelids persisting for up to 2 weeks; keratitis and iritis occureed in two-thirds of the animals. Corneal thickness, measured in vivo, increased by a maximum of 59% at 6 h, returning to normal by 9 days. 0.01 ml DCM produced similar, but less persistent effects on the conjunctiva and eyelids; keratitis was minor. Corneal thickness increased by up to 43% at 6 h, returning to normal by 9 days. Intraocular tension increased by 33% at 1 h, returning to control values by 3 days.10-min exposures to DCM vapour at concentrations up to 17 500 mg/m3 produced no macroscopic changes, but small increases in corneal thickness and intraocular tension occurred, which were related to the degree of exposure The mean peak increases in corneal thickness were 13% for 17 500 mg/m3 and 5% for 1750 mg/m3; corresponding values for increases in intraocular tension were 18% and 11%. Both corneal thickness and intraocular tension returned to normal by 2 days.Treatment with a decongestant preparation (Vasocon-A), containing an antihistamine and an α-adrenergic sympathomimetic, reduced both the inflammatory response and the rise in intraocular pressure caused by a splash contamination of the eye with liquid DCM. 相似文献
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