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41.
Antimitotic agents such as the clinically approved vinca alkaloids, taxanes and epothilone can arrest cell growth during interphase and are therefore among the most important drugs available for treating cancer. These agents suppress microtubule dynamics and thus interfere with intracellular transport, inhibit cell proliferation and promote cell death. Because these drugs target biological processes that are essential to all cells, they face an additional challenge when compared to most other drug classes. General toxicity can limit the applicable dose and therefore reduce therapeutic benefits. Photopharmacology aims to avoid these side-effects by introducing compounds that can be applied globally to cells in their inactive form, then be selectively induced to bioactivity in targeted cells or tissue during a defined time window. This review discusses photoswitchable analogues of antimitotic agents that have been developed by combining different photoswitchable motifs with microtubule-stabilizing or microtubule-destabilizing agents. 相似文献
42.
Shafiq Murad Susanne Michen Alexander Becker Monika Füssel Gabriele Schackert Torsten Tonn Frank Momburg Achim Temme 《International journal of molecular sciences》2022,23(10)
In glioblastoma, non-classical human leucocyte antigen E (HLA-E) and HLA-G are frequently overexpressed. HLA-E loaded with peptides derived from HLA class I and from HLA-G contributes to inhibition of natural killer (NK) cells with expression of the inhibitory receptor CD94/NKG2A. We investigated whether NK cells expressing the activating CD94/NKG2C receptor counterpart were able to exert anti-glioma effects. NKG2C+ subsets were preferentially expanded by a feeder cell line engineered to express an artificial disulfide-stabilized trimeric HLA-E ligand (HLA-E*spG). NK cells expanded by a feeder cell line, which facilitates outgrowth of conventional NKG2A+, and fresh NK cells, were included for comparison. Expansion via the HLA-E*spG feeder cells selectively increased the fraction of NKG2C+ NK cells, which displayed a higher frequency of KIR2DL2/L3/S2 and CD16 when compared to expanded NKG2A+ NK cells. NKG2C+ NK cells exhibited increased cytotoxicity against K562 and KIR:HLA-matched and -mismatched primary glioblastoma multiforme (GBM) cells when compared to NKG2A+ NK cells and corresponding fresh NK cells. Cytotoxic responses of NKG2C+ NK cells were even more pronounced when utilizing target cells engineered with HLA-E*spG. These findings support the notion that NKG2C+ NK cells have potential therapeutic value for treating gliomas. 相似文献
43.
Pablo de Vera Simone Taioli Paolo E. Trevisanutto Maurizio Dapor Isabel Abril Stefano Simonucci Rafael Garcia-Molina 《International journal of molecular sciences》2022,23(11)
Energetic carbon ions are promising projectiles used for cancer radiotherapy. A thorough knowledge of how the energy of these ions is deposited in biological media (mainly composed of liquid water) is required. This can be attained by means of detailed computer simulations, both macroscopically (relevant for appropriately delivering the dose) and at the nanoscale (important for determining the inflicted radiobiological damage). The energy lost per unit path length (i.e., the so-called stopping power) of carbon ions is here theoretically calculated within the dielectric formalism from the excitation spectrum of liquid water obtained from two complementary approaches (one relying on an optical-data model and the other exclusively on ab initio calculations). In addition, the energy carried at the nanometre scale by the generated secondary electrons around the ion’s path is simulated by means of a detailed Monte Carlo code. For this purpose, we use the ion and electron cross sections calculated by means of state-of-the art approaches suited to take into account the condensed-phase nature of the liquid water target. As a result of these simulations, the radial dose around the ion’s path is obtained, as well as the distributions of clustered events in nanometric volumes similar to the dimensions of DNA convolutions, contributing to the biological damage for carbon ions in a wide energy range, covering from the plateau to the maximum of the Bragg peak. 相似文献
44.
Manuel Lasch Kritika Sudan Corinna Paul Christian Schulz Thomas Kolben Julia van Dorp Sibel Eren Susanne Beyer Lorenzo Siniscalchi Sven Mahner Udo Jeschke Sarah Meister 《International journal of molecular sciences》2022,23(11)
(1) Background: Placental immune cells are playing a very important role in a successful placentation and the prevention of pregnancy complications. Macrophages dominate in number and relevance in the maternal and the fetal part of the placenta. The evidence on the polarization state of fetal and maternal macrophages involved in both, healthy and pregnancy-associated diseases, is limited. There is no representative isolation method for the direct comparison of maternal and fetal macrophages so far. (2) Material and Methods: For the isolation of decidual macrophages and Hofbauer cells from term placenta, fresh tissue was mechanically dissected and digested with trypsin and collagenase A. Afterwards cell enrichment was increased by a Percoll gradient. CD68 is represented as pan-macrophage marker, the surface markers CD80 and CD163 were further investigated. (3) Results: The established method revealed a high cell yield and purity of the isolated macrophages and enabled the comparison between decidual macrophages and Hofbauer cells. No significant difference was observed in the percentage of single CD163+ cells in the distinct macrophage populations, by using FACS and immunofluorescence staining. A slight increase of CD80+ cells could be found in the decidual macrophages. Considering the percentage of CD80+CD163− and CD80−CD163+ cells we could not find differences. Interestingly we found an increased number of double positive cells (CD80+CD163+) in the decidual macrophage population in comparison to Hofbauer cells. (4) Conclusion: In this study we demonstrate that our established isolation method enables the investigation of decidual macrophages and Hofbauer cells in the placenta. It represents a promising method for direct cell comparison, enzyme independently, and unaffected by magnetic beads, to understand the functional subsets of placental macrophages and to identify therapeutic targets of pregnancy associated diseases. 相似文献
45.
Sebastian Kummer Susanne Rinn Gunnar Seemann Nadine Bachmann Katherine Timothy Paul S. Thornton Frank Pillekamp Ertan Mayatepek Carsten Bergmann Thomas Meissner Niels Decher 《International journal of molecular sciences》2022,23(15)
The voltage-dependent L-type calcium channel isoform CaV1.2 is critically involved in many physiological processes, e.g., in cardiac action potential formation, electromechanical coupling and regulation of insulin secretion by beta cells. Gain-of-function mutations in the calcium voltage-gated channel subunit alpha 1 C (CACNA1C) gene, encoding the CaV1.2 α1-subunit, cause Timothy syndrome (TS), a multisystemic disorder that includes autism spectrum disorders and long QT (LQT) syndrome. Strikingly, TS patients frequently suffer from hypoglycemia of yet unproven origin. Using next-generation sequencing, we identified a novel heterozygous CACNA1C mutation in a patient with congenital hyperinsulinism (CHI) and associated hypoglycemic episodes. We characterized the electrophysiological phenotype of the mutated channel using voltage-clamp recordings and in silico action potential modeling experiments. The identified CaV1.2L566P mutation causes a mixed electrophysiological phenotype of gain- and loss-of-function effects. In silico action potential modeling supports that this mixed electrophysiological phenotype leads to a tissue-specific impact on beta cells compared to cardiomyocytes. Thus, CACNA1C variants may be associated with non-syndromic hyperinsulinemic hypoglycemia without long-QT syndrome, explained by very specific electrophysiological properties of the mutated channel. We discuss different biochemical characteristics and clinical impacts of hypoglycemia in the context of CACNA1C variants and show that these may be associated with significant morbidity for Timothy Syndrome patients. Our findings underline that the potential of hypoglycemia warrants careful attention in patients with CACNA1C variants, and such variants should be included in the differential diagnosis of non-syndromic congenital hyperinsulinism. 相似文献
46.
Frederik J. Hansen Zhiyuan Wu Paul David Anke Mittelstdt Anne Jacobsen Malgorzata J. Podolska Kenia Ubieta Maximilian Brunner Dina Kouhestani Izabela Swierzy Lotta Roßdeutsch Bettina Klsch Isabella Kutschick Susanne Merkel Axel Denz Klaus Weber Carol Geppert Robert Grützmann Alan Bnard Georg F. Weber 《International journal of molecular sciences》2022,23(9)
Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5′-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73+ B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73+ B-cells. Finally, neoadjuvant therapy correlated with reduced CD73+ B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73+ B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options. 相似文献
47.
Karl Fraser Scott J. Harrison Geoff A. Lane Don E. Otter Yacine Hemar Siew-Young Quek Susanne Rasmussen 《Food chemistry》2012
Tea is the second most consumed beverage in the world and its consumption has been associated with numerous potential health benefits. Factors such as fermentation methods, geographical origin and season can affect the primary and secondary metabolite composition of tea. In this study, a hydrophilic interaction liquid chromatography (HILIC) method coupled to high resolution mass spectrometry in both positive and negative ionisation modes was developed and optimised. The method when combined with principal component analysis to analyse three different types of tea, successfully distinguished samples into different categories, and provided evidence of the metabolites which differed between them. The accurate mass and high resolution attributes of the mass spectrometric data were utilised and relative quantification data were extracted post-data acquisition on 18 amino acids, showing significant differences in amino acid concentrations between tea types and countries. This study highlights the potential of HILIC chromatography combined with non-targeted mass spectrometric methods to provide a comprehensive understanding of polar metabolites in plant extracts. 相似文献
48.
Vera Lucia Arantes 《Journal of Materials Engineering and Performance》2012,21(8):1777-1784
Zirconium tin titanate (ZST) is often used as a dielectric resonator for the fabrication of microwave devices. Pure compositions do not sinter easily by solid state sintering; therefore, sintering ZST requires sintering aids capable of creating defects that could improve diffusion processes and/or promote liquid phase sintering. The mechanisms by which the additives influence the microstructure and, consequently, the ZSTs dielectric properties are not very clear. The effects of ZnO, Bi2O3, and La2O3, on the stoichiometry and dielectric properties of ZST sintered at different temperatures were investigated in this study. 相似文献
49.
Susanne Struck Doris Jaros Charles S. Brennan Harald Rohm 《International Journal of Food Science & Technology》2014,49(9):1963-1976
This review presents the state‐of‐the‐art concerning the application of natural and artificial high‐intensity sweeteners, fructans and bulking agents such as polyols as sugar replacers in sweet‐baked goods and their effects on product characteristics. The recent much publicised attention given to weight gain of the population and its consequences on the occurrence of diet‐related diseases in developed countries has influenced the food manufacturers attempts to provide the consumer with reduced energy products. The replacement of sucrose in sweet bakery products by alternative natural or artificial sweeteners can be a challenging issue. Sucrose as a main ingredient in sweet bakery products contributes, aside from providing sweetness, to numerous processing and product characteristics. Intense sweeteners have a high sweetness compared with sucrose but lack in their contribution to the body of the product, whereas the replacement of sucrose with bulking sweeteners may result in products with a similar body but a lack in taste and flavour. 相似文献
50.
Susanne Neugart Hans-Peter Kläring Michaela Zietz Monika Schreiner Sascha Rohn Lothar W. Kroh Angelika Krumbein 《Food chemistry》2012
The winter crop kale has a complex profile of different glycosylated and acylated flavonol glycosides which may be affected by global warming. To the best of our knowledge, compound–climate relationships for flavonol aglycones and flavonol glycosides were established for the first time. The investigated 10 major flavonol glycosides responded structure-dependent in the investigated temperature range between 0 and 12 °C and the photosynthetic active radiation range between 4 and 20 mol m−2 d−1, e.g. the decrease in temperature led to an increase in sinapic acid monoacylated and diacylated quercetin glycosides, while the sinapic acid monoacylated kaempferol glycosides showed a maximum at 4.5 °C. Furthermore, the hydroxycinnamic acid residues and the different number of glucose moieties in the 7-O position affected the response of kaempferol triglucosides. Consequently, global warming would result in lower concentrations of antioxidant-relevant quercetin glycosides in winter crops, suggesting a production at e.g. higher altitudes due to lower temperature. 相似文献