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《Drug discovery today》2022,27(6):1733-1742
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action. 相似文献
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BackgroundWomen suffering from kidney disease are more prone to fertility problems, due to uremia. Fortunately, their fertility rate increases dramatically after renal transplantation. This study analyzes the predictors/risk factors of successful pregnancy with live birth outcome while presenting an overview of the 7-year experience of a single center.MethodsThis retrospective cohort study includes 239 women of reproductive age (18–40 years) who underwent renal transplantation in a tertiary Turkish clinic between October 1, 2011, and August 24, 2017. The subjects were invited to take part in a survey questioning their obstetric characteristics and they were assessed in 2 groups: fertile and infertile. Multivariable linear regression analysis was conducted to determine the predictors of a successful pregnancy.ResultsThirty-five 35 patients wished to become pregnant: 12 got pregnant spontaneously, while 21 failed to become pregnant (spontaneously). The mean age of the patients at the survey was 34 ± 7. Regular menstrual cycles after renal transplantation, tacrolimus-mycophenolate mofetil maintenance protocol, and age at transplantation were found to be predictors of spontaneous pregnancy. The duration of peritoneal dialysis was significantly longer in the infertile group (48 vs 12 months).ConclusionEnd-stage renal disease's negative impacts, including menstrual abnormality and fertility problems, can be overcome by successful kidney transplantation with appropriate immunosuppression. Minimizing the duration of peritoneal dialysis, particularly in patients who desire future fertility, may be accepted as a logical management strategy. 相似文献
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Xiaoxv Dong Yawen Zeng Yi Liu Longtai You Xingbin Yin Jing Fu Jian Ni 《Phytotherapy research : PTR》2020,34(2):270-281
Aloe‐emodin is a naturally anthraquinone derivative and an active ingredient of Chinese herbs, such as Cassia occidentalis, Rheum palmatum L., Aloe vera, and Polygonum multiflorum Thunb. Emerging evidence suggests that aloe‐emodin exhibits many pharmacological effects, including anticancer, antivirus, anti‐inflammatory, antibacterial, antiparasitic, neuroprotective, and hepatoprotective activities. These pharmacological properties lay the foundation for the treatment of various diseases, including influenza virus, inflammation, sepsis, Alzheimer's disease, glaucoma, malaria, liver fibrosis, psoriasis, Type 2 diabetes, growth disorders, and several types of cancers. However, an increasing number of published studies have reported adverse effects of aloe‐emodin. The primary toxicity among these reports is hepatotoxicity and nephrotoxicity, which are of wide concern worldwide. Pharmacokinetic studies have demonstrated that aloe‐emodin has a poor intestinal absorption, short elimination half‐life, and low bioavailability. This review aims to provide a comprehensive summary of the pharmacology, toxicity, and pharmacokinetics of aloe‐emodin reported to date with an emphasis on its biological properties and mechanisms of action. 相似文献
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Naruemon Klaikeaw Jutamas Wongphoom Duangporn Werawatganon Maneerat Chayanupatkul Prasong Siriviriyakul 《World journal of hepatology》2020,12(7):363-377
BACKGROUND Aloe vera exerts several biological activities, such as, anti-inflammatory, antioxidant, and antimicrobial effects. It was recently shown to reduce insulin resistance and triglyceride level. We hypothesized that aloe vera would have beneficial effects in alleviating non-alcoholic steatohepatitis(NASH) in rats.AIM To examine the therapeutic effects of aloe vera in NASH rats.METHODS All rats were randomly divided into 3 groups(n = 6 in each group). Rats in the control group were fed ad libitum with a standard diet for 8 wk. Rats in the NASH group were fed ad libitum with a high-fat high-fructose diet(HFHFD) for 8 wk. Rats in the aloe vera group were fed ad libitum with a HFHFD and aloe vera in dimethylsulfoxide(50 mg/kg) by gavage daily for 8 wk. Liver samples were collected at the end of the treatment period.RESULTS Hepatic malondialdehyde(MDA) levels increased significantly in the NASH group as compared with the control group(377 ± 77 nmol/mg vs 129 ± 51 nmol/mg protein, respectively, P 0.001). Glutathione(GSH) levels were significantly lower in the NASH group than the control group(9 ± 2 nmol/mg vs 24 ± 8 nmol/mg protein, respectively, P = 0.001). The expression of interleukin-18(IL-18), nuclear factor-kappa β, and caspase-3 increased, while peroxisome proliferator-activated receptor gamma decreased in the NASH group compared with the controls. Following aloe vera administration, MDA levels decreased(199 ± 35 nmol/mg protein) and GSH increased(18 ± 4 nmol/mg protein) markedly. Steatosis, hepatocyte ballooning, lobular inflammation and increased hepatocyte apoptosis were observed in the NASH group. Aloe vera treatment attenuated these changes in liver histology.CONCLUSION Aloe vera attenuated oxidative stress, hepatic inflammation and hepatocyte apoptosis, thus improving liver pathology in rats with NASH. 相似文献
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D. Sforza G. Iaria L. Petagna A. Parente A. Anselmo F. Sergi S. Marzio F. Corrado S. Telli T.M. Manzia G. Tisone 《Transplantation proceedings》2019,51(1):140-142
Background
One daily dose of tacrolimus (QDT) improves adherence in kidney transplant (KT) recipients. A switch from twice-daily tacrolimus (BDT) to QDT showed similar efficacy and safety.Methods
The aim of our study was to demonstrate the long-term efficacy and safety of switching from BDT to QDT in KT recipients. Preliminary results have already been published. Forty-one patients (34 men and 7 women), mean age at KT of 43.9 ± 12.7 years, underwent a 1:1 dose switch from BDT to QDT; the mean time from KT to switch was 36.6 ± 16.1 months. In our study population, 4 patients received a living donor KT and 2 received a second allograft.Results
The mean follow-up was 86.8 ± 13 months from the switch and 126.2 ± 22.3 months from KT. Graft and patient survival rates were 90.2% and 95.1%, respectively. All patients maintained stable renal function during follow-up. During the first 3 months after the switch we observed a significant decrease in tacrolimus blood level (P = .0001). No significant differences were observed regarding tacrolimus dose before and after QDT introduction (P = not significant [NS]). Fourteen patients who stopped steroids under BDT treatment and 16 patients who stopped steroids after the switch are currently steroid-free.Conclusion
Our study showed safety and efficacy in switching from BDT to QDT. After early (<1 year) dose adjustment, tacrolimus blood levels remained stable throughout follow-up. Moreover, QDT represented a valid alternative for patients showing steroid side effects. 相似文献9.
闽产木立芦荟多糖的分离纯化及初步分析 总被引:14,自引:2,他引:12
目的 分离纯化及初步分析产木立芦荟中的多糖。方法 芦荟经沸水提取,醇沉,Sevage法去除蛋白质,Sephadex G-200柱色谱分离纯化,制得闽产木立芦荟多糖,以硫酸-苯酚法测定其总糖含量。结果 闽产木立芦荟多糖经紫外吸收光谱扫描具有多糖特征吸收峰,未见核酸和蛋白质吸收峰,多糖含量可达89.7%,初步分析由D-甘露糖和D-葡萄糖等单糖组成。结论 从闽产木立芦荟中可提取分离纯度较高的杂多糖。 相似文献
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K. Reynen U. Röber W.G. Daniel R. Henßge S. Schüler 《Clinical research in cardiology》1998,87(5):331-335
Zusammenfassung Zahlen zur H?ufigkeit von Herztumoren im operativen Krankengut liegen bisher für die Bundesrepublik Deutschland nicht vor.
Um einen entsprechenden überblick für das Jahr 1996 zu erhalten, wurde allen 77 herzchirurgischen Zentren der Bundesrepublik
Deutschland ein standardisierter Fragebogen zugesandt.
Daten von 65 der 77 Herzzentren (=84%) waren schlie?lich verfügbar: 187 Patienten waren wegen Myxomen, lediglich 44 wegen
nichtmyxomat?sen Tumoren, davon 28 wegen malignen prim?ren oder sekund?ren Herztumoren, operiert worden. Im Jahr 1996 waren
somit 0,32% (231/72 763) der Eingriffe mit Herz-Lungen-Maschine (erfa?t 72 763 von insgesamt 87 372) wegen eines Herztumors
vorgenommen worden. Ausgehend von diesen operativen Daten liegt die Inzidenz ausschlie?lich der prim?ren Tumoren des Herzens
zumindest bei 3 Tumoren pro 1 Million Einwohner pro Jahr (253 Tumoren/81,814 Millionen Einwohner). Wenn auch kleine Tumoren
asymptomatisch und unentdeckt bleiben k?nnen, wird heute doch die Mehrzahl prim?rer kardialer Tumoren durch Echokardiographie,
Computer- und Kernspintomographie bereits zu Lebzeiten des Patienten diagnostiziert, und diese Patienten werden in aller Regel
einer Operation zugeführt.
Somit werden gut 0,3% aller Eingriffe mit Herz-Lungen-Maschine in Deutschland wegen Herztumoren durchgeführt, wobei es sich
weit überwiegend um Myxome handelt.
Eingegangen: 23. September 1997, Akzeptiert: 11. Februar 1998 相似文献