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101.
Maria V. Deligiorgi Charis Liapi Dimitrios T. Trafalis 《International journal of molecular sciences》2020,21(23)
(1) Background: the present review provides a comprehensive and up-to date overview of the potential exploitation of fasting as an anticancer strategy. The rationale for this concept is that fasting elicits a differential stress response in the setting of unfavorable conditions, empowering the survival of normal cells, while killing cancer cells. (2) Methods: the present narrative review presents the basic aspects of the hormonal, molecular, and cellular response to fasting, focusing on the interrelationship of fasting with oxidative stress. It also presents nonclinical and clinical evidence concerning the implementation of fasting as adjuvant to chemotherapy, highlighting current challenges and future perspectives. (3) Results: there is ample nonclinical evidence indicating that fasting can mitigate the toxicity of chemotherapy and/or increase the efficacy of chemotherapy. The relevant clinical research is encouraging, albeit still in its infancy. The path forward for implementing fasting in oncology is a personalized approach, entailing counteraction of current challenges, including: (i) patient selection; (ii) fasting patterns; (iii) timeline of fasting and refeeding; (iv) validation of biomarkers for assessment of fasting; and (v) establishment of protocols for patients’ monitoring. (4) Conclusion: prescribing fasting as anticancer medicine may not be far away if large randomized clinical trials consolidate its safety and efficacy. 相似文献
102.
Dr. Christine Brotschi Dr. Martin H. Bolli Dr. John Gatfield Dr. Bibia Heidmann Dr. Francois Jenck Dr. Catherine Roch Dr. Thierry Sifferlen Dr. Alexander Treiber Dr. Jodi T. Williams Dr. Christoph Boss 《ChemMedChem》2020,15(5):430-448
The orexin system is responsible for regulating the sleep-wake cycle. Suvorexant, a dual orexin receptor antagonist (DORA) is approved by the FDA for the treatment of insomnia disorders. Herein, we report the optimization efforts toward a DORA, where our starting point was (5-methoxy-4-methyl-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-[5-(2-trifluoromethoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-pyrrolidin-1-yl}methanone ( 6 ), a compound which emerged from our in-house research program. Compound 6 was shown to be a potent, brain-penetrating DORA with in vivo efficacy similar to suvorexant in rats. However, shortcomings from low metabolic stability, high plasma protein binding (PPB), low brain free fraction (fu brain), and low aqueous solubility, were identified and hence, compound 6 was not an ideal candidate for further development. Our optimization efforts addressing the above-mentioned shortcomings resulted in the identification of (4-chloro-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-methyl-2-[5-(2-trifluoromethoxy-phenyl)-4H-[1,2,4]triazol-3-yl]-pyrrolidin-1-yl}l-methanone ( 42 ), a DORA with improved in vivo efficacy compared to 6 . 相似文献
103.
Suying Xu Adam C. Sedgwick Souad A. Elfeky Wenbo Chen Ashley S. Jones George T. Williams A. Toby A. Jenkins Steven D. Bull John S. Fossey Tony D. James 《Frontiers of Chemical Science and Engineering》2020,14(1):112
A boronic acid-based anthracene fluorescent probe was functionalised with an acrylamide unit to incorporate into a hydrogel system for monosaccharide detection. In solution, the fluorescent probe displayed a strong fluorescence turn-on response upon exposure to fructose, and an expected trend in apparent binding constants, as judged by a fluorescence response where D-fructose>D-galactose>D-mannose>D-glucose. The hydrogel incorporating the boronic acid monomer demonstrated the ability to detect monosaccharides by fluorescence with the same overall trend as the monomer in solution with the addition of D-fructose resulting in a 10-fold enhancement (≤0.25 mol/L). 相似文献
104.
Rosa Vera Oladis T. de Rincón Jesús Ramirez Bárbara Valverde Andrés Díaz-Gómez Rodrigo Sánchez-González 《工业材料与腐蚀》2020,71(7):1125-1137
In this study, the behavior of carbon steel and galvanized steel in nontropical coastal marine environments was evaluated. Evaluation was carried out with specimens with dimensions of 10 cm × 10 cm × 0.3 cm. These specimens were exposed to four testing stations (Iquique, Mejillones, Los Vilos, and San Vicente), where racks were installed both at ground level (ground), as well as in the upper zone of electrical transmission towers (tower). In each station, 24 specimens of A36 carbon steel and galvanized steel were placed (12 each). The corrosivity of the environment was measured using the ISO 9223, 9225, and 9226 standards. The specimens were evaluated on-site, monthly, through visual inspection and photographic record. Once withdrawn, the corrosion rate was determined and the corrosion products were analyzed through Raman and Fourier-transform infrared. The results show that, in all cases, the corrosion rate is greater in the tower than on the ground. However, even though the Los Vilos station is located farther from the sea (3,500 vs. ≈500 m), the corrosion rate of steel in the tower is the highest. This is caused by the generation of HCl from the transformation of lepidocrocite into goethite, in the presence of low chloride content, which acidifies the steel/corrosion product interface. In the case of galvanized steel, the corrosion rate is a function of the chloride content in the atmosphere, obtaining an excellent correlation between both parameters. 相似文献
105.
Dr. Dimitra T. Pournara Anna Durner Dr. Eftichia Kritsi Alexios Papakostas Dr. Panagiotis Zoumpoulakis Prof. Dr. Annette Nicke Dr. Maria Koufaki 《ChemMedChem》2020,15(24):2530-2543
The P2X7 receptor is a promising target for the treatment of various diseases due to its significant role in inflammation and immune cell signaling. This work describes the design, synthesis, and in vitro evaluation of a series of novel derivatives bearing diverse scaffolds as potent P2X7 antagonists. Our approach was based on structural modifications of reported (adamantan-1-yl)methylbenzamides able to inhibit the receptor activation. The adamantane moieties and the amide bond were replaced, and the replacements were evaluated by a ligand-based pharmacophore model. The antagonistic potency of the synthesized analogues was assessed by two-electrode voltage clamp experiments, using Xenopus laevis oocytes that express the human P2X7 receptor. SAR studies suggested that the replacement of the adamantane ring by an aryl-cyclohexyl moiety afforded the most potent antagonists against the activation of the P2X7 cation channel, with analogue 2-chloro-N-[1-(3-(nitrooxymethyl)phenyl)cyclohexyl)methyl]benzamide ( 56 ) exhibiting the best potency with an IC50 value of 0.39 μM. 相似文献
106.
Dr. Lilia Clima Bogdan Florin Craciun Dr. Andrea Angeli Andrea Petreni Alessandro Bonardi Dr. Alessio Nocentini Dr. Fabrizio Carta Prof. Paola Gratteri Prof. Mariana Pinteala Prof. Claudiu T. Supuran 《ChemMedChem》2020,15(21):2052-2057
We report novel molecules incorporating the nontoxic squalene scaffold and different carbonic anhydrase inhibitors (CAIs). Potent inhibitory action, in the low-nanomolar range, was detected against isoforms hCA II for sulfonamide derivatives, which proved to be selective against this isoform over the tumor-associate hCA IX and XII isoforms. On the other hand, coumarin derivatives showed weak potency but high selectivity against the tumor-associated isoform CA IX. These compounds are interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. In addition, an in silico study of inhibitor-bound hCA II revealed extensive interactions with the hydrophobic pocket of the active site and provided molecular insights into the binding properties of these new inhibitors. 相似文献
107.
Silicon - This study focus on the effects of silicon inclusion carbonaceous particulate on the hardness and microstructural properties of carburized low carbon steel, at constant temperature of... 相似文献
108.
Conceptual models for catalog-assisted design are developed to improve semantic modeling in the automation of design problems and the extraction of knowledge from engineering documents. The conceptual models are presented graphically. 相似文献
109.
Cristina-Daniela Ghițulică Andreia Cucuruz Georgeta Voicu Andrei T. Cucuruz Sorina Dinescu Aida Selaru Marieta Costache 《International Journal of Applied Ceramic Technology》2020,17(1):342-353
In this study, chemical precipitation methods were used to obtain ceramic materials doped with magnesium ions in order to improve the regeneration properties of materials used for tissue engineering. Two different ratios of magnesium oxide were used to dope the ceramic powder, more precisely 5% and 10%. The synthesized materials were characterized to determine the calcination temperature of the precursor powder by means of thermal analysis; to determine the mineralogical composition, X-ray diffraction was employed and the scanning electron microscopy was used to determine the microstructure. To make use of these ceramics as biomaterials, viability and proliferation cell tests have been performed. Since synthetic materials have several limitations with regard to medical applications, the materials based on HAp substituted with Mg ions are a promising solution for the regeneration of bone defects because they have a similar bone structure. The presence of Mg in the material proves to be beneficial because this element plays an important role in bone cell regeneration, and more specifically, in stimulating osteoblast proliferation. The materials synthesized in this work present a suitable morphology for uses in bone regeneration because they offer to cells a friendly environment for growth and anchoring. 相似文献
110.
Metal Science and Heat Treatment - Mechanical properties of copper-alloyed bainitic gray cast iron are studied after isothermal quenching for bainite at different temperatures and holds. The... 相似文献