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61.
Jason P. Holland Albert Kang Susan Cohrs Svetlana V. Selivanova Selena Milicevic Sephton Thomas Betzel Daniel Frey Mara Wieser Rolf Jaussi Richard A. Kammerer Roger Schibli Eliane Fischer 《化学与生物多样性》2013,10(4):538-555
Kinesin spindle protein (KSP), an ATP‐dependent motor protein, plays an essential role in bipolar spindle formation during the mitotic phase (M phase) of the normal cell cycle. KSP has emerged as a novel target for antimitotic anticancer drug development. In this work, we synthesized a range of new biphenyl compounds and investigated their properties in vitro as potential antimitotic agents targeting KSP expression. Antiproliferation (MTT (=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide)) assays, combined with fluorescence‐assisted cell sorting (FACS) and Western blot studies analyzing cell‐cycle arrest confirmed the mechanism and potency of these biphenyl compounds in a range of human cancer cell lines. Structural variants revealed that functionalization of biphenyl compounds with bulky aliphatic or aromatic groups led to a loss of activity. However, replacement of the urea group with a thiourea led to an increase in antiproliferative activity in selected cell lines. Further studies using confocal fluorescence microscopy confirmed that the most potent biphenyl derivative identified thus far, compound 7 , exerts its pharmacologic effect specifically in the M phase and induces monoaster formation. These studies confirm that chemical scope remains for improving the potency and treatment efficacy of antimitotic KSP inhibition in this class of biphenyl compounds. 相似文献
62.
Massimo Collino Mara Rogazzo Alessandro Pini Elisa Benetti Arianna Carolina Rosa Fausto Chiazza Roberto Fantozzi Daniele Bani Emanuela Masini 《Journal of cellular and molecular medicine》2013,17(11):1494-1505
Although recent preclinical and clinical studies have demonstrated that recombinant human relaxin (rhRLX) may have important therapeutic potential in acute heart failure and chronic kidney diseases, the effects of acute rhRLX administration against renal ischaemia/reperfusion (I/R) injury have never been investigated. Using a rat model of 1‐hr bilateral renal artery occlusion followed by 6‐hr reperfusion, we investigated the effects of rhRLX (5 μg/Kg i.v.) given both at the beginning and after 3 hrs of reperfusion. Acute rhRLX administration attenuated the functional renal injury (increase in serum urea and creatinine), glomerular dysfunction (decrease in creatinine clearance) and tubular dysfunction (increase in urinary excretion of N‐acetyl‐β‐glucosaminidase) evoked by renal I/R. These beneficial effects were accompanied by a significant reduction in local lipid peroxidation, free radical‐induced DNA damage and increase in the expression/activity of the endogenous antioxidant enzymes Mn‐ and CuZn‐superoxide dismutases (SOD). Furthermore, rhRLX administration attenuated the increase in leucocyte activation, as suggested by inhibition of myeloperoxidase activity, intercellular‐adhesion‐molecule‐1 expression, interleukin (IL)‐1β, IL‐18 and tumour necrosis factor‐α production as well as increase in IL‐10 production. Interestingly, the reduced oxidative stress status and neutrophil activation here reported were associated with rhRLX‐induced activation of endothelial nitric oxide synthase and up‐regulation of inducible nitric oxide synthase, possibly secondary to activation of Akt and the extracellular signal‐regulated protein kinase (ERK) 1/2, respectively. Thus, we report herein that rhRLX protects the kidney against I/R injury by a mechanism that involves changes in nitric oxide signalling pathway. 相似文献
63.
Elisa Fasoli Mara Colzani Giancarlo Aldini Attilio Citterio Pier Giorgio Righetti 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(8):1484-1491
Combinatorial peptide ligand libraries (CPLLs) have been adopted for investigating the proteomes of lemon peels and pulp, of a home-made alcoholic infusion of peels and of a very popular Italian liqueur called “Limoncello”, stated to be an infusion of the flavedo (the outer, yellow skin of lemons). The aim of this study was not only to perform the deepest investigation so far of the lemon peel proteome but also to assess the genuineness of the commercial liqueur via a three-pronged attack. First, different extraction techniques have been used for the characterization of the peel (and additionally of the pulp) proteome, secondly a home-made infusion has been analysed and finally the proteome of the commercial drink was checked. The peel (the flavedo, not the underlying layer called albedo) proteome has been evaluated via prior capture with CPLLs at different pH values (2.2 and 7.2). Via mass spectrometry analysis of the recovered fractions, after elution of the captured populations in 4% boiling SDS, we could identify a total of 1011 unique gene products in the peel extracts and 674 in the pulp, 264 proteins in the home-made infusion and just 8 proteins (and protein fragments), together with 12 peptides, in one Italian Limoncello produced in the Sorrento Region, thus proving the genuineness of this product. On the contrary, cheaper Limoncellos were devoid of any protein/peptide, casting doubts on their production from vegetable extracts. This could be the starting point for investigating the genuineness and natural origin of commercial drinks in order to protect consumers from adulterated products. 相似文献
64.
Marie Maraninchi Delphine Feron Ingrid Fruitier‐Arnaudin Audrey Bégu‐Le Corroller Juan P. Nogueira Julien Mancini René Valéro Jean M. Piot Bernard Vialettes 《Obesity (Silver Spring, Md.)》2013,21(2):378-381
Objective:
Hemorphin peptides exhibit biological activities that interfere with the endorphin system, the inflammatory response, and blood‐pressure control. VV‐hemorphin‐7 and LVV‐hemorphin‐7 peptides exert a hypotensive effect, in particular, by inhibiting the renin–angiotensin system. Furthermore, levels of circulating hemorphin‐7 peptides have been found to be decreased in diseases such as type 1 and type 2 diabetes.Design and Methods:
Because type 2 diabetes and obesity share common features, such as insulin resistance, microinflammation, high glomerular‐filtration rate (GFR), and cardiovascular risk, we evaluated serum VV‐hemorphin‐7 like immunoreactivity (VVH7‐i.r.) levels, using an enzyme‐linked immunosorbent assay method, on a group of 54 obese subjects without diabetes or hypertension, compared with a group of 33 healthy normal‐weight subjects.Results:
Circulating VVH7‐i.r. levels were significantly decreased in the obese group compared with the control group (1.98 ± 0.19 vs. 4.86 ± 0.54 µmol/l, respectively, P < 0.01), and a significant negative correlation between VVH7‐i.r. and diastolic blood pressure (DBP) was found in obese patients (r = ?0.35, P = 0.011). There was no significant correlation between VVH7‐i.r. level and insulin resistance, metabolic syndrome, or GFR.Conclusions:
The decreased serum hemorphin‐7 found in obese subjects, as in diabetes, may contribute to the development of hypertension and to the cardiovascular risk associated with these metabolic diseases.65.
Roberta Grande Domenico Corsi Raffaello Mancini Donatello Gemma Fabrizio Ciancola Isabella Sperduti Lorena Rossi Agnese Fabbri Maria G. Diodoro Enzo Ruggeri Germano Zampa Sara Bianchetti Teresa Gamucci 《PloS one》2013,8(12)
Background
Adjuvant chemotherapy (AC) in Stage II Colon Cancer (CC) is still under debate. Choice should be based on patients and disease characteristics. According to guidelines AC should be considered in high-risk T3N0 patients. No data are available for better option in low-risk patients. The aim of the study is to retrospectively evaluate relapse-free survival (RFS) and disease-free survival (DFS) according to treatment received in T3N0 CC.Methods
RFS and DFS are evaluated with Kaplan-Meier method. Multivariate Cox proportional hazard model was developed using stepwise regression, enter limit and remove limit were p = 0.10 and p = 0.15, respectively.Results
834 patients with T3N0 CC were recruited. Median age was 69 (29–93), M/F 463/371, 335 low-risk patients (40.2%), 387 high-risk (46.4%), 112 unknown (13.4%); 127 (15.2%) patients showed symptoms at diagnosis. Median sampled lymph nodes were 15 (1–76); 353 (42.3%) patients were treated with AC. Median follow up was 5 years (range 3–24). The 5-years RFS was 78.4% and the 5-years DFS was 76.7%. At multivariate analysis symptoms, lymph nodes, and adjuvant chemotherapy were prognostic factors for RFS. AC is prognostic factor for all endpoints.In low-risk group 5-years RFS was 87.3% in treated patients and 74.7% in non-treated patients (p 0.03); in high-risk group was respectively 82.7% and 71.4% (p 0.005).Conclusions
Data confirmed the role of known prognostic factors and suggest the relevance of adjuvant chemotherapy also in low-risk stage II T3N0 CC patients. However, the highest risk in low-risk subgroup should be identified to be submitted to AC. 相似文献66.
Darío C. Colautti Leandro Miranda Mariano Gonzalez-Castro Vanina Villanova Carlos A. Strüssmann Miguel Mancini Tomas Maiztegui Gustavo Berasain Ricardo Hattori Fabian Grosman Pablo Sanzano Ismael Lozano Sabina L. Vegh Victor Salinas Omar Del Ponti Pamela del Fresno Priscila Minotti Yoji Yamamoto Claudio R. M. Baigún 《Journal of fish biology》2020,96(1):202-216
In South America, the order Atheriniformes includes the monophyletic genus Odontesthes with 20 species that inhabit freshwater, estuarine and coastal environments. Pejerrey Odontesthes argentinensis is widely distributed in coastal and estuarine areas of the Atlantic Ocean and is known to foray into estuaries of river systems, particularly in conditions of elevated salinity. However, to our knowledge, a landlocked self-sustaining population has never been recorded. In this study, we examined the pejerrey population of Salada de Pedro Luro Lake (south-east of Buenos Aires Province, Argentina) to clarify its taxonomic identity. An integrative taxonomic analysis based on traditional meristic, landmark-based morphometrics and genetic techniques suggests that the Salada de Pedro Luro pejerrey population represents a novel case of physiological and morphological adaptation of a marine pejerrey species to a landlocked environment and emphasises the environmental plasticity of this group of fishes. 相似文献
67.
Plant species vary in their growth response to arbuscular mycorrhizal (AM) fungi, with responses ranging from negative to positive. Differences in response to AM fungi may affect competition between plant species, influencing their ability to coexist. We hypothesized that positively responding species, whose growth is stimulated by AM fungi, will experience stronger intraspecific competition and weaker interspecific competition in soil containing AM fungi, while neutrally or negatively responding species should experience weaker intraspecific and stronger interspecific competition. We grew Plantago lanceolata, which responds positively to AM fungi, and Bromus inermis, which responds negatively to AM fungi, in an additive response surface competition experiment that varied the total density and relative frequency of each species. Plants were grown in sterilized background soil that had been inoculated with whole soil biota, which includes AM fungi, or a microbial wash, that contained other soil microbes but no AM fungi, or in sterilized soil that contained no biota. The positively responding P. lanceolata was more strongly limited by intraspecific than interspecific competition when AM fungi were present. By contrast, the presence of AM fungi decreased the strength of intraspecific competition experienced by the negatively responding B. inermis. Because AM fungi are almost always present in soil, strong intraspecific competition in positively responding species would prevent them from outcompeting species that respond neutrally or negatively to AM fungi. The potential for increased intraspecific competition to offset growth benefits of AM fungi could, therefore, be a stabilizing mechanism that promotes coexistence among plant species. 相似文献
68.
Sara Bruschini Simona di Martino Maria Elena Pisanu Luigi Fattore Claudia De Vitis Valentina Laquintana Simonetta Buglioni Eugenio Tabbì Andrea Cerri Paolo Visca Gabriele Alessandrini Francesco Facciolo Christian Napoli Marcella Trombetta Antonio Santoro Anna Crescenzi Gennaro Ciliberto Rita Mancini 《Journal of cellular physiology》2020,235(3):1877-1887
69.
70.
Claudio Napoli Alberto Zullo Antonietta Picascia Teresa Infante Francesco Paolo Mancini 《Journal of cellular biochemistry》2013,114(1):7-20
In recent years, the diagnosis of cardiovascular disease (CVD) has increased its potential, also thanks to mass spectrometry (MS) proteomics. Modern MS proteomics tools permit analyzing a variety of biological samples, ranging from single cells to tissues and body fluids, like plasma and urine. This approach enhances the search for informative biomarkers in biological samples from apparently healthy individuals or patients, thus allowing an earlier and more precise diagnosis and a deeper comprehension of pathogenesis, development and outcome of CVD to further reduce the enormous burden of this disease on public health. In fact, many differences in protein expression between CVD‐affected and healthy subjects have been detected, but only a few of them have been useful to establish clinical biomarkers because they did not pass the verification and validation tests. For a concrete clinical support of MS proteomics to CVD, it is, therefore, necessary to: ameliorate the resolution, sensitivity, specificity, throughput, precision, and accuracy of MS platform components; standardize procedures for sample collection, preparation, and analysis; lower the costs of the analyses; reduce the time of biomarker verification and validation. At the same time, it will be fundamental, for the future perspectives of proteomics in clinical trials, to define the normal protein maps and the global patterns of normal protein levels, as well as those specific for the different expressions of CVD. J. Cell. Biochem. 114: 7–20, 2012. © 2012 Wiley Periodicals, Inc. 相似文献