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31.
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
32.
Akiko Suzuki Mina Minamide Chihiro Iwaya Kenichi Ogata Junichi Iwata 《International journal of molecular sciences》2020,21(23)
Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. Here, we aim to provide a comprehensive review of the cellular metabolism involved in bone development and homeostasis, as revealed by mouse genetic studies. 相似文献
33.
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
34.
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
35.
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
36.
Devendrasinh Darbar M.R. Anilkumar Vijayaraghavan Rajagopalan Indranil Bhattacharya Hendry Izaac Elim T. Ramakrishnappa F.I. Ezema Rajan Jose M.V. Reddy 《Ceramics International》2018,44(5):4630-4639
Optimization of electrodes for charge storage with appropriate processing conditions places significant challenges in the developments for high performance charge storage devices. In this article, metal cobaltite spinels of formula MCo2O4 (where M = Mn, Zn, Fe, Ni and Co) are synthesized by oxalate decomposition method followed by calcination at three typical temperatures, viz. 350, 550, and 750 °C and examined their performance variation when used as anodes in lithium ion batteries. Phase and structure of the materials are studied by powder x-ray diffraction (XRD) technique. Single phase MnCo2O4,ZnCo2O4 and Co3O4 are obtained for all different temperatures 350 °C, 550 °C and 750 °C; whereas FeCo2O4 and NiCo2O4 contained their constituent binary phases even after repeated calcination. Morphologies of the materials are studied via scanning electron microscopy (SEM): needle-shaped particles of MnCo2O4 and ZnCo2O4, submicron sized particles of FeCo2O4 and agglomerated submicron particle of NiCo2O4 are observed. Galvanostatic cycling has been conducted in the voltage range 0.005–3.0 V vs. Li at a current density of 60 mA g?1 up to 50 cycles to study their Li storage capabilities. Highest observed charge capacities are: MnCo2O4 – 365 mA h g?1 (750 °C); ZnCo2O4 – 516 mA h g?1 (550 °C); FeCo2O4 – 480 mA h g?1 (550 °C); NiCo2O4 – 384 mA h g?1 (750 °C); and Co3O4 – 675 mA h g?1 (350 °C). The Co3O4 showed the highest reversible capacity of 675 mA h g?1; the NiO present in NiCo2O4 acts as a buffer layer that results in improved cycling stability; the ZnCo2O4 with long needle-like shows good cycling stability. 相似文献
37.
Kumar Nikhil Verma A. K. Sardana Sahil Sarkar K. Singh T. N. 《Bulletin of Engineering Geology and the Environment》2018,77(2):595-608
Bulletin of Engineering Geology and the Environment - Landslides that occur due to the rapid motion of a rock-mass are a primary risk in mountainous terrains and are a danger to human life and... 相似文献
38.
Grechkoseev A. K. Krasil’shchikov M. N. Kruzhkov D. M. Mararescul T. A. 《Journal of Computer and Systems Sciences International》2020,59(4):598-608
Journal of Computer and Systems Sciences International - We consider the problem of refining the evolving Earth Orientation Parameters (EOP) used during the converting from the inertial coordinate... 相似文献
39.
Differences between oculomotor and perceptual artifacts for temporally limited head mounted displays
Alexander Goettker Kevin J. MacKenzie T. Scott Murdison 《Journal of the Society for Information Display》2020,28(6):509-519
We used perceptual and oculomotor measures to understand the negative impacts of low (phantom array) and high (motion blur) duty cycles with a high‐speed, AR‐likehead‐mounted display prototype. We observed large intersubject variability for the detection of phantom array artifacts but a highly consistent and systematic effect on saccadic eye movement targeting during low duty cycle presentations. This adverse effect on saccade endpoints was also related to an increased error rate in a perceptual discrimination task, showing a direct effect of display duty cycle on the perceptual quality. For high duty cycles, the probability of detecting motion blur increased during head movements, and this effect was elevated at lower refresh rates. We did not find an impact of the temporal display characteristics on compensatory eye movements during head motion (e.g., VOR). Together, our results allow us to quantify the tradeoff of different negative spatiotemporal impacts of user movements and make subsequent recommendations for optimized temporal HMD parameters. 相似文献
40.
Neural Processing Letters - The fuzzy time series modeling techniques proposed in this study are based on a fuzzy inference method in which the fuzzy output is either a so-called pliant or quasi... 相似文献