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Transcriptional down regulation of hTERT and senescence induction in HepG2 cells by chelidonine

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World Journal of Gastroenterology 2009年第29期15卷 3603-3610页

作者： Sakineh Kazemi Noureini michael wink Department of Biology Faculty of Basic Science Tarbiat Moallem University of Sabzevar Sabzevar Iran Department of Biology Institute of Pharmacy and Molecular Biotechnology Heidelberg University INF 364 69120 Heidelberg Germany

AIm： To investigate the potential effects of chelidonine, the main alkaloid of Chelidonium majus, on telomerase activity and its regulation in HepG2 cells. mETHODS： Cytotoxicity of chelidonine for HepG2 cells was determined by neutral red assay. A modified polymerase chain reaction （PCR）-based telomerase repeat amplification protocol was used to estimate relative telomerase activity in chelidonine-treated cells in comparison with the untreated control cells. Relative expression level of the catalytic subunit of telomerase （hTERT） gene and P-glycoprotein （pgp） were estimated using semi-quantitative real-time reverse transcription-PCR （RT-PCR）. Cell senescence in treated cells was demonstrated using a 13-galactosidase test. RESULTS： Cytotoxicity of chelidonine in HepG2 cells was not dose-dependent and tended to reach plateau immediately after the living cells were reduced in number to slightly higher than 50%. However, 12 μmol/L concentration of chelidonine was considered as LD50, where the maximal attainable effects were realized. Real-time RT-PCR data showed that the expression of pgp increased three-fold in chelidonine treated HepG2 cells in comparison with the untreated controls. moP phologically, treated HepG2 cells showed apoptotic features after 24 h and a small fraction of cells appeared with single blister cell death. The relative expression level of Bcl-2 dropped to less than 50% of control cells at a sub-apoptotic concentration of chelidonine and subsequently increased to higher than 120% at LD50. Telomerase activity was reduced considerably after administration of very low doses of chelidonine, whereas higher concentrations of chelidonine did not remarkably enhance the effect. Real-time RT-PCR experiments indicated a drastic decrease in expression level of hTERT subunit of telomerase under treatment with chelidonine. Repeated treatment of cells with very low doses of chelidonine caused a decline in growth rate by 4 wk and many of the cells appeared to be a

关键词： Chelidonine Telomerase Inhibition Apoptosis Senescence

Degradation of intestinal mRNA:A matter of treatment

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World Journal of Gastroenterology 2015年第12期21卷 3499-3508页

作者： Sabine Heumüller-Klug Carsten Sticht Karin Kaiser Elvira wink Cornelia Hagl Lucas Wessel Karl-Herbert Schafer Department of Pediatric Surgery mannheim Medical University of Heidelberg medical Research Centre mannheim Medical University of Heidelberg University of Applied Sciences Kaiserslautern

AIm: To characterize the influence of location, species and treatment upon RNA degradation in tissue samples from the gastrointestinal tract. mETHODS: The intestinal samples were stored in different medium for different times under varyingconditions: different species(human and rat), varying temperature(storage on crushed ice or room temperature), time point of dissection of the submucous-mucous layer from the smooth muscle(before or after storage), different rinsing methods(rinsing with medium, PBS, RNALater or without rinsing at all) and different regions of the gut(proximal and distal small intestine, caecum, colon and rectum). The total RNA from different parts of the gut(rat: proximal and distal small intestine, caecum, colon and rectum, human: colon and rectum) and individual gut layers(muscle and submucosal/mucosal) was extracted. The quality of the RNA was assessed by micro capillary electrophoresis. The RNA quality was expressed by the RNA integrity number which is calculated from the relative height and area of the 18 S and 28 S RNA peaks. From rat distal small intestine q PCR was performed for neuronal and glial ***: RNA obtained from smooth muscle tissue is much longer stable than those from submucosal/mucosal tissue. At RT muscle RNA degrades after one day, on ice it is stable at least three days. Cleaning and separation of gut layers before storage and use of RNALater, maintains the stability of muscle RNA at RT for much longer periods. Different parts of the gut show varying degradation periods. RNA obtained from the submucosal/mucosal layer always showed a much worse amplification rate than RNA from muscle tissue. In general RNA harvested from rat tissue, either smooth muscle layer or submucosal/mucosal layer is much longer stable than RNA from human gut tissue, and RNA obtained from smooth muscle tissue shows an increased stability compared to RNA from submucosal/mucosal tissue. At RT muscle RNA degrades after one day, while the stabilit

关键词： Key words:Intestinal RNA Degradation Storing conditions Flushing Cooling

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解决特殊生产问题的气举装置

油气田开发工程译丛 1989年第8期 17-20页

作者： wink.,HW 吴孟君

Expanding the Therapeutic Spectrum of Artemisinin:Activity Against Infectious Diseases Beyond malaria and Novel Pharmaceutical Developments

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World Journal of Traditional Chinese medicine 2016年第2期2卷 1-23页

作者： Thomas Efferth marta R.Romero Anna Rita Bilia Ahmed Galal Osman mahmoud ElSohly michael wink Rudolf Bauer Ikhlas Khan maria Camilla Bergonzi Jose J.G.marin Department of Pharmaceutical Biology Institute of Pharmacy and Biochemistry Johannes Gutenberg University Experimental Hepatology and Drug Targeting (HEVEFARm) CIBERehd IBSAL University of SalamancaCampus Miguel de Unamuno Department of Chemistry "Ugo Schiff" University of Florence National Center for Natural Products Research School of Pharmacy University of Mississippi ElSohly Laboratories Inc. Department of Pharmaceutics University of Mississippi Institute of Pharmacy and molecular Biotechnology Ruprecht-Karls University Institute of Pharmaceutical Sciences Department of Pharmacognosy University of Graz Devision of Pharmacognosy Department of Biomolecular Sciences University of Mississippi

The interest of Western medicine in Traditional Chinese medicine(TCm) as a source of drug leads/new drugs to treat diseases without available efficient therapies has been dramatically augmented in the last decades by the extensive work and the outstanding findings achieved within this kind of medicine. The practice of TCm over thousands of years has equipped scientists with substantial experience with hundreds of plants that led to the discovery of artemisinin(qinghaosu), which is extracted from the medicinal plant Artemisia annua L.(qinghao). The unexpected success of artemisinin in combating malaria has drawn strong attention from the scientific community towards TCm. Artemisinin was discovered by Youyou Tu in 1972. Since then, several novel pharmacological activities based on the well-known properties of the sesquiterpene lactone structure with the oxepane ring and an endoperoxide bridge have been unravelled. Beyond malaria, artemisinin and its derivatives(artemisinins) exert profound activities towards other protozoans(Leishmania, Trypanosoma, amoebas, Neospora caninum, and Eimeria tenella), trematodes(Schistosoma, liver flukes), and viruses(human cytomegalovirus, hepatitis B and C viruses). Less clear is the effect against bacteria and fungi. Based on the promising results of artemisinin and the first generation derivatives(artesunate, artemether, arteether), novel drug development strategies have been *** included the synthesis of acetal-and non-acetal-type artemisinin dimeric molecules as well as developing nanotechnological approaches, ***-based liposomes, niosomes, micelles, solid lipid nanocarriers, nanostructured lipid carriers, nanoparticles, fullerenes and nanotubes. The current review presents an overview on different aspects of artemisinins, including sources, chemistry, biological/pharmacological properties, types of infectious pathogens that are susceptible to artemisinins in vitro and in vivo, in addition to the advancement in

关键词： Artemisinin derivatives Artemisia annua Asteraceae Antimalarial drugs Anti-pathogen activity Antiviral properties Artemisinin-loaded nanocarriers Traditional Chinese medicine

两种β-受体阻断剂心得静和mepin-dolol正常人临床和血流动力学的比较研究

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中国临床药理学杂志 1985年第1期 72-73页

作者： wink.K

mepindolol是一种新的β-受体阻断剂。本文报告在7名23～34岁男性正常志愿者中进行的mepindolol与心得静临床和血流动力学的比较研究结果。

关键词：心得静静息比较研究对照组吲哚洛尔血流动力 mepin-dolol

Natural Products modulate the multifactorial multidrug Resistance of Cancer

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