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Werner Hoffmann 《International journal of molecular sciences》2015,16(8):19153-19169
Gastric cancer is still a leading cause of cancer-related mortality worldwide in spite of declining incidence. Gastric cancers are, essentially, adenocarcinomas and one of the strongest risk factors is still infection with Helicobacter pylori. Within the last years, it became clear that gastric self-renewal and carcinogenesis are intimately linked, particularly during chronic inflammatory conditions. Generally, gastric cancer is now regarded as a disease resulting from dysregulated differentiation of stem and progenitor cells, mainly due to an inflammatory environment. However, the situation in the stomach is rather complex, consisting of two types of gastric units which show bidirectional self-renewal from an unexpectedly large variety of progenitor/stem cell populations. As in many other tumors, cancer stem cells have also been characterized for gastric cancer. This review focuses on the various gastric epithelial stem cells, how they contribute to self-renewal and which routes are known to gastric adenocarcinomas, including their stem cells. 相似文献
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Annika Jahn Anton Hoffmann Luisa Blaesing Fabian Kunde Martin Bertau Martina Bremer Steffen Fischer 《化学,工程师,技术》2020,92(11):1733-1740
The enzymatic conversion of lignins, possibly in combination with electrochemical oxidation, makes aromatics such as syringol, guaiacol, vanillin and catechol available in the qualities required by the fragrance industry. The lignins were obtained by soda digestion from wheat straw and Miscanthus, characterized and then converted with laccases. The overall yield amounted up to 9 wt % with a product spectrum confined to four substances. Catechol was the major product, with a fraction of ≈75 %. It can easily be isolated by extraction with acetone. 相似文献
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Steffen Vojacek Lukas Schulig Nathalie Wössner Norman Geist Prof. Dr. Walter Langel Prof. Dr. Manfred Jung Prof. Dr. Dennis Schade Prof. Dr. Andreas Link 《ChemMedChem》2019,14(8):853-864
Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp3 hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC50 value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling. 相似文献
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Dr. Li Di Prof. Per Artursson Dr. Alex Avdeef Prof. Leslie Z. Benet Prof. J. Brian Houston Dr. Manfred Kansy Edward H. Kerns Prof. Hans Lennernäs Dr. Dennis A. Smith Prof. Kiyohiko Sugano 《ChemMedChem》2020,15(20):1862-1874
Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients. 相似文献
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Diese Recherche zeigt, dass sich die Bedeutung, die dem Thema RFID in den Medien und der ?ffentlichen Diskussion derzeit beigemessen
wird, auch in der Anzahl der im Internet zu findenden Seiten niederschl?gt. Dabei bewegt sich die Qualit?t der betrachteten
Angebote überwiegend auf einem hohen Niveau, was vor allem auf Seiten der kommerziellen Anbieter nicht weiter verwundert,
da es sich bei RFID doch um einen zunehmend st?rker umk?mpften Markt handelt, auf dem es hei?t, potenzielle Kunden für sich
zu akquirieren. Es darf mit Spannung erwartet werden, wie sich das Informationsangebot wandelt, wenn tats?chlich das prognostizierte
exponentielle Wachstum des RFID-Marktes eintritt. 相似文献
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The curing of diglycidyl ether of bisphenol A (DGEBA) with 2,6-dimethylol-p-cresol modified by hexahydrophthalic acid anhydride was investigated and compared with the analogous in situ curing of DGEBA, hexahydrophthalic acid anhydride and 2,6-dimethylol-p-cresol. The chemical reactions were investigated by means of titration and different spectroscopic and chromatographic methods. It was examined whether the less complicated and therefore cheaper in situ reaction delivers postcured products with equal or better properties. Furthermore, it was investigated whether the results are similar using technical phenolic hardeners. 相似文献
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An analytical solution is presented to the problem of steady groundwater flow seeping into a pumped cylindrical hole partially penetrating a homogeneous and anisotropic confined aquifer overlying a gravel substratum. Solutions are obtained for two general cases of the problem: (1) when the level of the pumped hole is below the confining layer; (2) when it is above it. The validity of the proposed theory is tested by comparing analytical predictions obtained for a few flow situations with corresponding results obtained by numerical means. The theory presented here can be utilized to convert the rate of rise of water in a pumped auger hole into directional conductivities of soil, in areas where water is found to be in a confined state overlying a gravel substratum. The study shows that the conductivity values calculated by neglecting the confining pressure of an artesian aquifer with a gravel base [i.e., by applying the existing (Boast and Kirkham in 1971), auger hole seepage theory for a phreatic aquifer with a gravel base to confined situations] may result in serious error; hence, the artesian head of an aquifer must be accounted for while computing the conductivity values. Further, it is observed that the area contributing flow to a pumped auger hole/well with a gravel base is mostly restricted to a short radial distance from the center of the hole, particularly for situations where the gravel substratum is located close to the bottom of the hole. This is in contrast to auger hole flow situations overlying an impervious substratum, where the domain contributing flow is mostly spread out to a considerable distance from the center of the hole. 相似文献