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991.
Emma Langella Dr. Sébastien Pierre Dr. Wadih Ghattas Dr. Michel Giorgi Dr. Marius Réglier Dr. Michele Saviano Dr. Luciana Esposito Dr. Renaud Hardré Dr. 《ChemMedChem》2010,5(9):1568-1576
Specific inhibition of the copper‐containing peptidylglycine α‐hydroxylating monooxygenase (PHM), which catalyzes the post‐translational modification of peptides involved in carcinogenesis and tumor progression, constitutes a new approach for combating cancer. We carried out a structure–activity study of new compounds derived from a well‐known PHM substrate analogue, the olefinic compound 4‐phenyl‐3‐butenoic acid (PBA). We designed, synthesized, and tested various PBA derivatives both in vitro and in silico. We show that it is possible to increase PBA affinity for PHM by appropriate functionalization of its aromatic nucleus. Compound 2 d , for example, bears a meta‐benzyloxy substituent, and exhibits better inhibition features (Ki=3.9 μM , kinact/Ki=427 M ?1 s?1) than the parent PBA (Ki=19 μM , kinact/Ki=82 M ?1 s?1). Docking calculations also suggest two different binding modes for PBA derivatives; these results will aid in the development of further PHM inhibitors with improved features. 相似文献
992.
Michele Dei Cas Ileana Vigentini Sara Vitalini Antonella Laganaro Marcello Iriti Rita Paroni Roberto Foschino 《International journal of molecular sciences》2021,22(1)
Given the pharmacological properti es and the potential role of kynurenic acid (KYNA) in human physiology and the pleiotropic activity of the neurohormone melatonin (MEL) involved in physiological and immunological functions and as regulator of antioxidant enzymes, this study aimed at evaluating the capability of Saccharomyces cerevisiae EC1118 to release tryptophan derivatives (dTRPs) from the kynurenine (KYN) and melatonin pathways. The setting up of the spectroscopic and chromatographic conditions for the quantification of the dTRPs in LC-MS/MS system, the optimization of dTRPs’ production in fermentative and whole-cell biotransformation approaches and the production of dTRPs in a soybean-based cultural medium naturally enriched in tryptophan, as a case of study, were included in the experimental plan. Variable amounts of dTRPs, with a prevalence of metabolites of the KYN pathway, were detected. The LC-MS/MS analysis showed that the compound synthesized at highest concentration is KYNA that reached 9.146 ± 0.585 mg/L in fermentation trials in a chemically defined medium at 400 mg/L TRP. Further experiments in a soybean-based medium confirm KYNA as the main dTRPs, whereas the other dTRPs reached very lower concentrations. While detectable quantities of melatonin were never observed, two MEL isomers were successfully measured in laboratory media. 相似文献
993.
Michele Regina Rosa Hamester Daniel Felipe Pietezak Carla Dalmolin Daniela Becker 《应用聚合物科学杂志》2021,138(33):50817
This work evaluates the effects of the crystallinity degree and π–π interactions between nanoparticles and a polymeric matrix on the electrical properties of polyamides and carbon nanotubes (CNT) nanocomposites. Two polymeric matrices were chosen; polyamide (PA) 6.6, a semi-crystalline polymer, and PA 6I-6T (here called aPA), a semi-aromatic and amorphous polyamide. The PA 6.6 crystallinity degree did not significantly change. Both lamellar thicknesses, amorphous (La) and crystalline (Lc), were estimated through Small-angle X-ray scattering. La increased significantly when CNTs were added. Both nanocomposites presented almost the same percolation threshold. In aPA nanocomposites, the π–π interaction between aromatic groups of CNTs and aPA is not only responsible for a homogeneous CNT dispersion, but also creates a direct path, parallel to the electrodes, for electron conduction after the percolation limit. In the PA 6.6 nanocomposites, the CNTs preferably disperse in the amorphous regions, forming a conductive network. 相似文献
994.
Roberta Zuntini Elena Bonora Laura Maria Pradella Laura Benedetta Amato Michele Vidone Sara De Fanti Irene Catucci Laura Cortesi Veronica Medici Simona Ferrari Giuseppe Gasparre Paolo Peterlongo Marco Sazzini Daniela Turchetti 《International journal of molecular sciences》2021,22(11)
The NBN gene has been included in breast cancer (BC) multigene panels based on early studies suggesting an increased BC risk for carriers, though not confirmed by recent research. To evaluate the impact of NBN analysis, we assessed the results of NBN sequencing in 116 BRCA-negative BC patients and reviewed the literature. Three patients (2.6%) carried potentially relevant variants: two, apparently unrelated, carried the frameshift variant c.156_157delTT and another one the c.628G>T variant. The latter was subsequently found in 4/1390 (0.3%) BC cases and 8/1580 (0.5%) controls in an independent sample, which, together with in silico predictions, provided evidence against its pathogenicity. Conversely, the rare c.156_157delTT variant was absent in the case-control set; moreover, a 50% reduction of NBN expression was demonstrated in one carrier. However, in one family it failed to co-segregate with BC, while the other carrier was found to harbor also a probably pathogenic TP53 variant that may explain her phenotype. Therefore, the c.156_157delTT, although functionally deleterious, was not supported as a cancer-predisposing defect. Pathogenic/likely pathogenic NBN variants were detected by multigene panels in 31/12314 (0.25%) patients included in 15 studies. The risk of misinterpretation of such findings is substantial and supports the exclusion of NBN from multigene panels. 相似文献
995.
Nicola Alessio Carmela Belardo Maria Consiglia Trotta Salvatore Paino Serena Boccella Francesca Gargano Gorizio Pieretti Flavia Ricciardi Ida Marabese Livio Luongo Umberto Galderisi Michele DAmico Sabatino Maione Francesca Guida 《International journal of molecular sciences》2021,22(7)
The bioactive form of vitamin D, 1,25-dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2-3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive—activated and proliferative—phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased β-galactosidase (B-gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator-activated-receptor-alpha (PPAR-α), reduced most of these effects. Morphological analysis of ex-vivo microglia obtained from vitamin-D-deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D. 相似文献
996.
Sabrina Nicol Michele Tanturli Giorgio Mattiuz Alberto Antonelli Ilaria Baccani Chiara Bonaiuto Simone Baldi Giulia Nannini Marta Menicatti Gianluca Bartolucci Gian Maria Rossolini Amedeo Amedei Maria Gabriella Torcia 《International journal of molecular sciences》2021,22(12)
Persistent infection with High Risk-Human Papilloma Viruses (HR-HPVs) is a primary cause of cervical cancer worldwide. Vaginal-dysbiosis-associated bacteria were correlated with the persistence of HR-HPVs infection and with increased cancer risk. We obtained strains of the most represented bacterial species in vaginal microbiota and evaluated their effects on the survival of cervical epithelial cells and immune homeostasis. The contribution of each species to supporting the antiviral response was also studied. Epithelial cell viability was affected by culture supernatants of most vaginal-dysbiosis bacteria, whereas Lactobacillus gasseri or Lactobacillus jensenii resulted in the best stimulus to induce interferon-γ (IFN-γ) production by human mononuclear cells from peripheral blood (PBMCs). Although vaginal-dysbiosis-associated bacteria induced the IFN-γ production, they were also optimal stimuli to interleukin-17 (IL-17) production. A positive correlation between IL-17 and IFN-γ secretion was observed in cultures of PBMCs with all vaginal-dysbiosis-associated bacteria suggesting that the adaptive immune response induced by these strains is not dominated by TH1 differentiation with reduced availability of IFN-γ, cytokine most effective in supporting virus clearance. Based on these results, we suggest that a vaginal microbiota dominated by lactobacilli, especially by L. gasseri or L. jensenii, may be able to assist immune cells with clearing HPV infection, bypasses the viral escape and restores immune homeostasis. 相似文献
997.
Evangelia Ioannidou Michele Moschetta Sidrah Shah Jack Steven Parker Mehmet Akif Ozturk George Pappas-Gogos Matin Sheriff Elie Rassy Stergios Boussios 《International journal of molecular sciences》2021,22(18)
Prostate cancer (PC) is the most common cancer in men and the second leading cause of cancer-related death worldwide. Many therapeutic advances over the last two decades have led to an improvement in the survival of patients with metastatic PC, yet the majority of these patients still succumb to their disease. Antiagiogenic therapies have shown substantial benefits for many types of cancer but only a marginal benefit for PC. Ongoing clinical trials investigate antiangiogenic monotherapies or combination therapies. Despite the important role of angiogenesis in PC, clinical trials in refractory castration-resistant PC (CRPC) have demonstrated increased toxicity with no clinical benefit. A better understanding of the mechanism of angiogenesis may help to understand the failure of trials, possibly leading to the development of new targeted anti-angiogenic therapies in PC. These could include the identification of specific subsets of patients who might benefit from these therapeutic strategies. This paper provides a comprehensive review of the pathways involved in the angiogenesis, the chemotherapeutic agents with antiangiogenic activity, the available studies on anti-angiogenic agents and the potential mechanisms of resistance. 相似文献
998.
Biochemical applications of mass spectrometry (MS) are important in the pharmaceutical industry. They comprise compositional analyses of biomolecules, especially proteins, and methods that measure molecular functions such as ligand binding. In early drug discovery, MS is used to characterize essential reagents and in structural biology. A number of MS-based methods have been proposed for use in high-throughput screening (HTS), but are unlikely to supplant established radiometric and fluorometric methods for this purpose. These methods, which include pulsed-ultrafiltration MS, frontal affinity chromatography-MS, and size-exclusion chromatography-MS, may ultimately be most successful in the post-screening lead development phase. In full development, MS is used heavily in the search for biomarkers that can be used to gauge disease progression and drug action. This review gives equal attention to the technical aspects of MS-based methods and to selective pressures present in the industrial environment that influence their chances of gaining wide application. 相似文献
999.
1000.
Michele Dondi Claudio Iglesias Eduardo Dominguez Guia Guarini Mariarosa Raimondo 《Applied Clay Science》2008,40(1-4):143-158
The Patagonian kaolins offer a wide set of origin of deposits, composition, mineral processing and ceramic properties, giving a rare opportunity for investigating the interdependence of mineralogy, chemical composition, particle size distribution, texture, and surface activity with their technological behaviour in sanitaryware and porcelain stoneware production. Plasticity is strictly dependent on surface activity, < 2 μm fraction and expandable clay minerals; slip rheology is affected by soluble salts and expandable clay minerals, but also by high specific surface or tubular halloysite. Kaolinite/halloysite play an opposite role versus smectite/interstratified I/S in slip casting and tile pressing: the former allow faster casting rates, while the latter improve powder flowability and mechanical strength. Kaolinite and quartz are beneficial for drying behaviour while high surface activity or expandable clay minerals increase significantly drying sensitivity. Firing behaviour is mainly affected by minor components supplying “fluxing” (i.e. iron, alkali and alkaline-earth) oxides. A great deal of technological parameters seem to be reasonably predicted by the surface activity of clays and especially the Methylene Blue index, which is the most reliable, simple and economic method to predict and control the ceramic response of kaolins and ball clays. 相似文献