Clinical Assessment on the Safety and Potential Efficacy of Mesenchymal Stem Cells Preconditioned With Ethionamide (ET-STEM) in Patients With Frontotemporal Dementia (FTD)

The primary purpose of this study is to evaluate the safety and the tolerability of 3 repeated doses of ET-STEM (Mesenchymal stem cells preconditioned with ethionamide) in patients with FTD.

开始日期2022-07-06

申办/合作机构

Samsung Medical Center

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100 项与 Mesenchymal stem cells(Samsung Medical Center) 相关的转化医学

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项与 Mesenchymal stem cells(Samsung Medical Center) 相关的文献（医药）

2023-03-17·International journal of molecular sciences

Synthesis and Evaluation on the Fungicidal Activity of S-Alkyl Substituted Thioglycolurils.

Article

作者: Popkov, Sergey V. ; Vinogradova, Ekaterina E. ; Alekseenko, Anna L. ; Kravchenko, Angelina N. ; Kolotyrkina, Natalya G. ; Gazieva, Galina A.

A series of S-alkyl substituted thioglycolurils was prepared through the alkylation of corresponding thioglycolurils with halogenoalkanes and tested for their fungicidal activity against six phytopathogenic fungi from different taxonomic classes: Venturia inaequalis, Rhizoctonia solani, Fusarium oxysporum, Fusarium moniliforme, Bipolaris sorokiniana, and Sclerotinia sclerotiorum, and two pathogenic yeasts: Candida albicans and Cryptococcus neoformans var. grubii. A number of S-alkyl substituted thioglycolurils exhibited high activity against Venturia inaequalis and Rhizoctonia solani (85-100% mycelium growth inhibition), and moderate activity against other phytopathogens. S-Ethyl substituted thioglycolurils possessed a high activity against Candida albicans. Additionally, the hemolytic and cytotoxic properties of promising derivatives were determined using human red blood cells and human embryonic kidney cells, respectively. Two S-ethyl derivatives possessed both low cytotoxicity against normal human cells and high fungicidal activity against Candida albicans.

2019-03-01·Drug Metabolism and Disposition2区 · 医学

Breast Cancer Resistance Protein and Multidrug Resistance Protein 2 Determine the Disposition of Esculetin-7-O-Glucuronide and 4-Methylesculetin-7-O-Glucuronide

2区 · 医学

Article

作者: Luo, Guangkuo ; Qi, Xiaoxiao ; Sun, Rongjin ; Li, Yuhuan ; Ou, Xiaojun ; Hu, Ming ; Zhu, Lijun ; Song, Wenjie ; Xie, Yushan ; Liu, Zhongqiu ; Wang, Ying

Esculetin (ET)-7-O-glucuronide (ET-G) and 4-methylesculetin (4-ME)-7-O-glucuronide (4-ME-G) are the main glucuronide of ET and 4-ME, respectively. The disposition mediated by efflux transporters for glucuronide has significant influence on the pharmacokinetic profile and efficacy of bioactive compounds. In the current study, transporter gene knockout mice and Caco-2 cells were used to explore the effects of breast cancer resistance protein (BCRP) and multidrug resistance-associated protein 2 (MRP2) on the disposition of ET-G and 4-ME-G. After oral or i.v. administration of ET and 4-ME, the area under the plasma concentration-time curve from time 0 to the last data point or infinity values of ET, 4-ME, and their glucuronides (ET-G and 4-ME-G) were remarkably and significantly increased in most Bcrp1^-/- and Mrp2^-/- mice compared with those in wild-type FVB mice (P < 0.05). These results were accompanied with a significant increase of maximum plasma concentration values (P < 0.05). In Caco-2 monolayers, the efflux and clearance rates of ET-G and 4-ME-G were markedly reduced by the BCRP inhibitor Ko143 and MRP2 inhibitor MK571 on the apical side (P < 0.05). In an intestinal perfusion study, the excretion of ET-G was significantly decreased in perfusate and increased in plasma in Bcrp1^-/- mice compared with those in wild-type FVB mice (P < 0.05). The 4-ME-G concentration was also decreased in the bile in transporter gene knockout mice. ET and 4-ME showed good permeability in both Caco-2 monolayers [apparent permeability (P_app ) ≥ 0.59 × 10^-5 cm/s] and duodenum (P_app ≥ 1.81). In conclusion, BCRP and MRP2 are involved in excreting ET-G and 4-ME-G. ET and 4-ME are most likely absorbed via passive diffusion in the intestines.

2018-05-01·The Journal of Steroid Biochemistry and Molecular Biology2区 · 生物学

Simultaneous profiles of sulfonated androgens, sulfonated estrogens and sulfonated progestogens in postpubertal boars (sus scrofa domestica) measured by LC–MS/MS

2区 · 生物学

Article

作者: Wudy, S A ; Sánchez-Guijo, A ; Hartmann, M F ; Schuler, G

Sulfonated steroids (s-St) have been usually regarded as inactive metabolites but are progressively considered as precursors for the intra-tissue formation of bioactive steroids. Moreover, independent effects without preceding removal of the sulfate group have been observed. We use the porcine testicular-epididymal compartment as a model to investigate the still largely unknown s-St physiology as the boar exhibits an intriguingly broad s-St spectrum predominantly originating from the testis. The application of LC-MS/MS in steroidomics enables the determination of unconjugated and intact sulfonated steroids with currently highest specificity and good sensitivity, allowing the concurrent measuring of numerous analytes in larger quantities of samples. Profiles (6h, 20min intervals) were generated for sulfonated 5-androstene-3ß,17ß-diol (Adiol-S), androsterone (A-S), dehydroepiandrosterone (DHEA-S), epiandrosterone (EA-S), epitestosterone (ET-S), estrone (E1-S), estradiol-17β (E2-S), pregnenolone (P5-S), 17αOH-pregnenolone (OHP5-S) and unconjugated testosterone (T) in four unstimulated and four hCG-stimulated boars. Moreover, concentrations were measured in individual samples collected from testicular afferent and efferent blood to differentiate between testicular vs. extratesticular origin. Highest concentrations were found for EA-S, followed by ET-S, Adiol-S and DHEA-S, which mostly exceeded the levels of E1-S and A-S. Lowest concentrations were obtained for E2-S, P5-S and OHP5-S. The analytical profile also included sulfonated T, 5α-dihydrotestosterone and cholesterol. However, their concentrations were below the limit of quantification. Profiles of quantifiable s-St were consistent with a wave-like pattern associated with T pulses. In postpartal females (n=5) concentrations of all analytes assessed were undetectable, suggesting that in pigs the adrenals are not a quantitatively significant source of s-St.

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