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61.
Myriam Gonzlez María Ovejero-Snchez Alba Vicente-Blzquez Raquel lvarez Ana B. Herrero Manuel Medarde Rogelio Gonzlez-Sarmiento Rafael Pelez 《International journal of molecular sciences》2021,22(4)
Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers. 相似文献
62.
Shamila Vibhushan Manuela Bratti Juan Eduardo Montero-Hernndez Alaa El Ghoneimi Marc Benhamou Nicolas Charles Eric Daugas Ulrich Blank 《International journal of molecular sciences》2021,22(1)
A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions. 相似文献
63.
Lorena Rodríguez-López Myriam Rincón-Fontán Xanel Vecino Ana B. Moldes Jose M. Cruz 《Journal of surfactants and detergents》2020,23(1):79-90
Over the last few years, the global biosurfactant market has raised due to the increasing awareness among consumers, for the use of biological or bio-based products. Because of their composition, it can be speculated that these are more biocompatible and more biodegradable than their chemical homologous. However, at the moment, no studies exist in the literature about the biodegradability of biosurfactants. In this work, a biosurfactant contained in a crude extract, obtained from a corn wet-milling industry stream that ferments spontaneously in the presence of lactic acid bacteria, was subjected to a biodegradation study, without addition of external microbial biomass, under different conditions of temperature (5–45 °C), biodegradation time (15–55 days), and pH (5–7). For that, a Box–Behnken factorial design was applied, which allowed to predict the percentage of biodegradation for the biosurfactant contained in the crude extract, between the range of the independent variables selected in the study, obtaining biodegradation values between 3 and 80%. The percentage of biodegradation for the biosurfactant was calculated based on the increase in the surface tension of samples of the crude extract. Furthermore, it was also possible to predict the variation in t1/2 for the biosurfactant (time to achieve the 50% of biodegradation) under different conditions. 相似文献
64.
Bican Osman Bayça Salih Uğur Kuleyin Hamdi Gümrük Recep 《Metal Science and Heat Treatment》2021,63(3-4):156-162
Metal Science and Heat Treatment - The effect of solid boronizing at 950°C for 2 and 4 h on the phase composition, microstructure, hardness and abrasive wear of steel AISI 304L is studied... 相似文献
65.
D. Solís-Cortés E. Navarrete-Astorga J.L. Costa-Krämer J. Salguero-Fernandez R. Schrebler D. Leinen E.A. Dalchiele J.R. Ramos-Barrado F. Martín 《Ceramics International》2019,45(5):5577-5587
C-axis textured thin films of gallium-doped indium zinc oxide (GIZO) with a 2% ratio of Ga/Zn, were obtained via RF-magnetron sputtering with high transparency and electrical conductivity. A Box-Behnken response surface design was used to evaluate the effects of the deposition parameters (In2O3 target power, deposition time, and substrate temperature) on the chemical composition, optical, electrical, and structural properties of the GIZO films. The optical constants and the electrical properties were obtained using optical models. The GIZO stoichiometry, and therefore the In/Zn atomic ratio, affected the crystallinity, crystalline parameters, band gap, and charge carrier mobility of the GIZO films. The charge carrier density was related to the change in the crystalline parameters of the hexagonal structure and the In/Zn atomic ratio. The best electrical conductivity values (1.75?×?103 Ω?1 cm?1) were obtained for GIZO films with In/Zn ratio ≥?1. Several figures of merit (FOM) defined for the visible and solar regions were comparatively used to select the optimal In/Zn atomic ratio that provided the best balance between the conductivity and the transparency. The optimal In/Zn ratio was in a range of 0.85–0.90 for the GIZO films. 相似文献
66.
Martin Michálek Monika Michálková Gurdial Blugan Jakob Kuebler 《Ceramics International》2018,44(3):3255-3260
Up to now, commercially available alumina ceramics were claimed to have strength between 400 and 550 MPa. However, our study shows strength ~ 2 times higher for commercially available alumina than commonly believed. The average and characteristic strength, measured on 31 pure alumina ceramic discs by ball on three balls (B3B) test, were 1205 ± 93 MPa and 1257 MPa, respectively, with a Weibull modulus of m = 11.8. Tested specimens were in form of discs with a diameter of 5 mm and thickness 0.5 mm. The grain size distribution of the alumina is bimodal with an average grain size of ~ 850 nm measured at the surface. The fracture reveals a mixed transgranular / intergranular failure mode. To avoid incorporation of additional flaws, the discs were tested as sintered. The characteristic flexural strength measured in B3B was recalculated according to Weibull theory for standard 4-point bending bars of size 3 × 4 × 45 mm as bend 856 MPa. The measured strength of nearly 900 MPa shows the potential of strength for high purity alumina ceramics. 相似文献
67.
68.
László Lőrincz Máté Zsemberi György Bánsághi Tamás Sohajda Edit Székely 《化学工程与技术》2018,41(7):1466-1472
Chiral molecules, especially enantiomers and diastereomers of purity > 99 %, present a significant market share within the chemical, pharmaceutical, and flavor industries. Antisolvent precipitations, both batch and semicontinuous operations to serve the current trends in flow chemistry were demonstrated to be environmentally benign and efficient tools in achieving high optical purities. Although salts are known to be insoluble in supercritical CO2, instabilities of the nascent salts were detected and applied for increasing efficiency. Diastereomeric excess values of the crystalline products exceeded 99 % in maximum of three consecutive steps both by repeated resolution with half molar equivalent of the amine to the acid and by direct recrystallization of the salts. 相似文献
69.
Abraham G. Alvarado Rosaura Hernández-Montelongo Martin Rabelero Lourdes A. Pérez-Carrillo Jorge E. Puig Francisco López-Serrano 《Polymer Engineering and Science》2020,60(2):223-232
A simple but comprehensive model considering homogeneous and micellar nucleation, coagulation, entry of radicals to particles and to micelles and radicals' exit from particles, is presented. The model is validated, in a starved semicontinuous heterophase polymerization of ethyl methacrylate, at three monomer addition rates. The model accurately describes the overall and instantaneous conversion, the average particle density and diameter, and the number and weight average molar masses evolutions over time. It is found that even though the average number of radicals is much smaller than 0.5, the system is not 0-1. An empirical function was used to describe the gel effect. The homogeneous nucleation was the prevailing mechanism for particle formation and large exit rates of radicals were observed. POLYM. ENG. SCI., 60: 223–232, 2019. © 2019 Society of Plastics Engineers 相似文献
70.