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71.
David S. Goodsell Michel F. Sanner Arthur J. Olson Stefano Forli 《Protein science : a publication of the Protein Society》2021,30(1):31-43
The AutoDock suite provides a comprehensive toolset for computational ligand docking and drug design and development. The suite builds on 30 years of methods development, including empirical free energy force fields, docking engines, methods for site prediction, and interactive tools for visualization and analysis. Specialized tools are available for challenging systems, including covalent inhibitors, peptides, compounds with macrocycles, systems where ordered hydration plays a key role, and systems with substantial receptor flexibility. All methods in the AutoDock suite are freely available for use and reuse, which has engendered the continued growth of a diverse community of primary users and third‐party developers. 相似文献
72.
Anti-angiogenic therapy has recently been added to the panel of cancer therapeutics, but predictive biomarkers of response are still not available. In animal models, anti-angiogenic therapy causes tumor starvation by increasing hypoxia and impairing nutrients supply. It is thus conceivable that angiogenesis inhibition causes remarkable metabolic perturbations in tumors, although they remain largely uncharted. We review here recent acquisitions about metabolic effects of angiogenesis blockade in tumors and discuss the possibility that some metabolic features of tumor cells - i.e. their dependency from glucose as primary energy substrate - might affect tumor responses to anti-VEGF treatment. 相似文献
73.
Francesca Giampieri Md Soriful Islam Stefania Greco Massimiliano Gasparrini Tamara Y. Forbes Hernandez Giovanni Delli Carpini Stefano Raffaele Giannubilo Andrea Ciavattini Bruno Mezzetti Luca Mazzoni Franco Capocasa Mario Castellucci Maurizio Battino Pasquapina Ciarmela 《Journal of cellular physiology》2019,234(5):7622-7633
Uterine leiom yomas are benign tumors highly prevalent in reproductive women. In thecurrent study, initially, we aimed to screen five different strawberry cultivars (Alba, Clery, Portola, Tecla, and Romina) to identify efficient cultivars in terms of phytochemical characterization and biological properties by measuring phenolic and anthocyanin content as well as antioxidant capacity, and by measuring apoptotic rate and reactive oxygen species (ROS) production in uterine leiomyoma cells. Next, we focused on the most efficient ones, cultivar Alba (A) and Romina (R) as well as Romina anthocyanin (RA) fraction for their ability to regulate oxidative phosphorylation (oxygen consumption rate [OCR]) glycolysis (extracellular acidification rate [ECAR]), and also fibrosis. Leiomyoma and myometrial cells were treated with a methanolic extract of A and R (250 μg/ml) or with RA (50 μg/ml) for 48 hr to measure OCR and ECAR, as well as gene expression associated with fibrosis. In the leiomyoma cells, RA was more effective in inducing apoptosis and increasing intracellular ROS levels, followed by R and A. In myometrial cells, all strawberry treatments increased the cellular viability and decreased ROS concentrations. Leiomyoma cells showed also a significant decrease in ECAR, especially after RA treatment, while OCR was slightly increased in both myometrial and leiomyoma cells. R and RA treatment significantly decreased collagen 1A1, fibronectin, versican, and activin A messenger RNA expression in leiomyoma cells. In conclusion, this study suggests that Romina, or its anthocyanin fraction, can be developed as a therapeutic and/or preventive agent for uterine leiomyomas, confirming the healthy effects exerted by these fruits and their bioactive compounds. 相似文献
74.
Giovanni?Micaletto Maria?Cristina?GambiEmail author Stefano?Piraino 《Polar Biology》2003,26(5):327-333
The large scale-worm Laetmonice producta Grube 1877 is the most abundant aphroditid polychaete in Antarctic coastal waters. We investigated the demographic structure and some reproductive features of different L. producta populations from high-Antarctic (Weddell Sea) and Antarctic Peninsula (King George Island) shelf bottoms, collected in summer 1996 (ANT-XIII/3, EASIZ I cruise) and autumn 2000 (ANT-XVII/3, EASIZ III cruise). L. producta in the studied geographic areas showed a wide bathymetric range (200-850 m depth), and a different size distribution pattern with depth, characterised by a reduction of large specimens in the deepest stations. The species is gonochoric, with females more abundant in specimens of larger sizes. Eggs at different stages of maturation (ranging from 40 to 320 wm in diameter) were examined in 270 individuals from different stations and size classes. Egg size showed a slightly bimodal trend, with largely overlapping egg cohorts, suggesting a continuous reproduction, and a long-lasting gametogenesis. Significant differences (Kolmogorov-Smirnov test, P<0.05) in egg-size frequency distribution were detected only when data of the two geographic areas were compared (Weddell Sea vs King George Island), and not according to stations within each area, and females' size. The two sets of geographic samples were collected in different seasons and therefore it was not possible to assess if differences observed are due to sampling time or to geographic factors. Mature spermatozoa were recognisable only in autumn male specimens from King George Island, and showed a rounded nucleus and a short conical acrosome. Occurrence of an endosymbiont polychaete, Veneriserva pygoclava meridionalis (new sub-species of Dorvilleidae), was recorded in the coelomic cavity of 163 specimens of L. producta, 125 of which were from the deepest station of the Weddell Sea (stn. 14, 850 m depth). L. producta females with and without the endosymbiont did not show differences in egg-size distribution. The reproductive features of L. producta, together with its large size and slow growth, seem typical of a long-living predator species, and uncoupled from the typical summer environmental conditions and the pulsating system of coastal Antarctic waters. 相似文献
75.
A novel cationic fluorescent zinc (Zn2+) indicator (RhodZin-3) with nanomolar affinity for Zn2+ has been synthesized. RhodZin-3 exhibits large pH-independent fluorescence increases in the orange region of the visible wavelength spectrum with increasing zinc concentrations, and no sensitivity to physiologically relevant Ca2+ concentrations. Experiments in neuronal cell cultures show that RhodZin-3 effectively localizes into mitochondria and detects changes of intramitochondrial free Zn2+ ([Zn2+]m). 相似文献
76.
Stefano Toldo Rachel W. Goehe Marzia Lotrionte Eleonora Mezzaroma Evan T. Sumner Giuseppe G. L. Biondi-Zoccai Ignacio M. Seropian Benjamin W. Van Tassell Francesco Loperfido Giovanni Palazzoni Norbert F. Voelkel Antonio Abbate David A. Gewirtz 《PloS one》2013,8(3)
Purpose
The antineoplastic efficacy of anthracyclines is limited by their cardiac toxicity. In this study, we evaluated the toxicity of doxorubicin, non-pegylated liposomal-delivered doxorubicin, and epirubicin in HL-1 adult cardiomyocytes in culture as well as in the mouse in vivo.Methods
The cardiomyocytes were incubated with the three anthracyclines (1 µM) to assess reactive oxygen generation, DNA damage and apoptotic cell death. CF-1 mice (10/group) received doxorubicin, epirubicin or non-pegylated liposomal-doxorubicin (10 mg/kg) and cardiac function was monitored by Doppler echocardiography to measure left ventricular ejection fraction (LVEF), heart rate (HR) and cardiac output (CO) both prior to and 10 days after drug treatment.Results
In HL-1 cells, non-pegylated liposomal-doxorubicin generated significantly less reactive oxygen species (ROS), as well as less DNA damage and apoptosis activation when compared with doxorubicin and epirubicin. Cultured breast tumor cells showed similar sensitivity to the three anthracyclines. In the healthy mouse, non-pegylated liposomal doxorubicin showed a minimal and non-significant decrease in LVEF with no change in HR or CO, compared to doxorubicin and epirubicin.Conclusion
This study provides evidence for reduced cardiac toxicity of non-pegylated-liposomal doxorubicin characterized by attenuation of ROS generation, DNA damage and apoptosis in comparison to epirubicin and doxorubicin. 相似文献77.
78.
Mahdavinia M Bishehsari F Verginelli F Cumashi A Lattanzio R Sotoudeh M Ansari R Semeraro D Hormazdi M Fakheri H Rakhshani N De Lellis L Curia MC Cama A Piantelli M Malekzadeh R Iacobelli S Mariani-Costantini R 《Journal of cellular physiology》2008,216(2):543-550
CRC-associated P53 mutations have not been studied extensively in non-Western countries at relatively low CRC risk. We examined, for the first time, 196 paraffin-embedded CRC cases from Northern Iran for mutations in P53 exons 5-8 using PCR-direct sequencing. P53 status and mutation site/type were correlated with nuclear protein accumulation, clinicopathologic variables and data on K-ras mutations and high-level microsatellite instability (MSI-H). We detected 96 P53 mutations in 87 (44.4%) cases and protein accumulation in 84 cases (42.8%). P53 mutations correlated directly with stage and inversely with MSI-H. Distal CRCs were more frequently mutated at major CpG hotspot codons [248 (8/66, 12.1%), 175 (7/66, 10.6%), and 245 (7/66, 10.6%)], while in proximal tumors codon 213, emerged as most frequently mutated (5/28, 17.9% vs. 3/66, 4.5%, P = 0.048). Transitions at CpGs, the most common mutation type, were more frequent in non-mucinous (25% vs. 10.4% in mucinous, P = 0.032), and distal CRC (27% vs. 12.5% in proximal, P = 0.02), and correlated with K-ras transversions. Transitions at non-CpGs, second most common P53 mutation, were more frequent in proximal tumors (15.6% vs. 4.7% in distal, P = 0.01), and correlated with K-ras transitions and MSI-H. Overall frequency and types of mutations and correlations with P53 accumulation, stage and MSI-H were as reported for non-Iranian patients. However P53 mutation site/type and correlations between P53 and K-ras mutation types differed between proximal and distal CRC. The codon 213 P53 mutation that recurred in proximal CRC was previously reported as frequent in esophageal cancer from Northern Iran. 相似文献
79.
Structural and biochemical insights into 7β‐hydroxysteroid dehydrogenase stereoselectivity 下载免费PDF全文
Simone Savino Erica Elisa Ferrandi Federico Forneris Stefano Rovida Sergio Riva Daniela Monti Andrea Mattevi 《Proteins》2016,84(6):859-865
Hydroxysteroid dehydrogenases are of great interest as biocatalysts for transformations involving steroid substrates. They feature a high degree of stereo‐ and regio‐selectivity, acting on a defined atom with a specific configuration of the steroid nucleus. The crystal structure of 7β‐hydroxysteroid dehydrogenase from Collinsella aerofaciens reveals a loop gating active‐site accessibility, the bases of the specificity for NADP+, and the general architecture of the steroid binding site. Comparison with 7α‐hydroxysteroid dehydrogenase provides a rationale for the opposite stereoselectivity. The presence of a C‐terminal extension reshapes the substrate site of the β‐selective enzyme, possibly leading to an inverted orientation of the bound substrate. Proteins 2016; 84:859–865. © 2016 Wiley Periodicals, Inc. 相似文献
80.
Stefano Caffarri Roman Kouřil Sami Kereïche Egbert J Boekema Roberta Croce 《The EMBO journal》2009,28(19):3052-3063
Photosystem II (PSII) is a large multiprotein complex, which catalyses water splitting and plastoquinone reduction necessary to transform sunlight into chemical energy. Detailed functional and structural studies of the complex from higher plants have been hampered by the impossibility to purify it to homogeneity. In this work, homogeneous preparations ranging from a newly identified particle composed by a monomeric core and antenna proteins to the largest C2S2M2 supercomplex were isolated. Characterization by biochemical methods and single particle electron microscopy allowed to relate for the first time the supramolecular organization to the protein content. A projection map of C2S2M2 at 12 Å resolution was obtained, which allowed determining the location and the orientation of the antenna proteins. Comparison of the supercomplexes obtained from WT and Lhcb‐deficient plants reveals the importance of the individual subunits for the supramolecular organization. The functional implications of these findings are discussed and allow redefining previous suggestions on PSII energy transfer, assembly, photoinhibition, state transition and non‐photochemical quenching. 相似文献