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91.
Rossella Fioravanti Veronica Rodriguez Jonatan Caroli Ugo Chianese Rosaria Benedetti Elisabetta Di Bello Beatrice Noce Clemens Zwergel Davide Corinti Dolores Via Lucia Altucci Andrea Mattevi Sergio Valente Antonello Mai 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):973
As regioisomers/bioisosteres of 1a, a 4-phenylbenzamide tranylcypromine (TCP) derivative previously disclosed by us, we report here the synthesis and biological evaluation of some (hetero)arylbenzoylamino TCP derivatives 1b-6, in which the 4-phenyl moiety of 1a was shifted at the benzamide C3 position or replaced by 2- or 3-furyl, 2- or 3-thienyl, or 4-pyridyl group, all at the benzamide C4 or C3 position. In anti-LSD1-CoREST assay, all the meta derivatives were more effective than the para analogues, with the meta thienyl analogs 4b and 5b being the most potent (IC50 values = 0.015 and 0.005 μM) and the most selective over MAO-B (selectivity indexes: 24.4 and 164). When tested in U937 AML and prostate cancer LNCaP cells, selected compounds 1a,b, 2b, 3b, 4b, and 5a,b displayed cell growth arrest mainly in LNCaP cells. Western blot analyses showed increased levels of H3K4me2 and/or H3K9me2 confirming the involvement of LSD1 inhibition in these assays. 相似文献
92.
Buzzini P Romano S Turchetti B Vaughan A Pagnoni UM Davoli P 《FEMS yeast research》2005,5(4-5):379-385
Thirty-seven basidiomycetous yeasts belonging to 30 species of seven genera were grown on media containing l-cysteine or l-methionine as sole nitrogen sources with the objective of evaluating volatile organic sulfur compound (VOSC) production. The headspace of yeast cultures was analyzed by the solid-phase microextraction (SPME) sampling method, and volatile compounds were quantified and identified by GC-MS techniques. Ten strains assimilating L-methionine produced the following VOSCs: 3-(methylthio)-1-propanol, methanethiol, S-methyl thioacetate, dimethyl disulfide, dimethyl trisulfide, allyl methyl sulphide and 4,5-dihydro-3(2H)-thiophenone. Production was <1 mgl(-1) except for 3-(methylthio)-1-propanol of which between 40 and 400 mgl(-1) was synthesized. Higher alcohols (isobutyl alcohol, isoamyl alcohol and active amyl alcohol) and esters (ethyl acetate, ethyl propionate, n-propyl acetate, isobutyl acetate, n-propyl propionate, n-butyl acetate, isoamyl acetate, amyl acetate, isoamyl propionate, amyl propionate and 2-phenylmethyl acetate) were also sporadically produced. This is the first report of VOSCs production by basidiomycetous yeasts. Consequently, basidiomycetous yeasts may be considered an interesting new group of microbial VOSCs producers for the flavor industry. 相似文献
93.
Vindigni V Mazzoleni F Rossini K Fabbian M Zanin ME Bassetto F Carraro U 《Plastic and reconstructive surgery》2004,114(6):1509-15; discussion 1516-8
Skeletal muscle regeneration is a powerful, naturally occurring process of tissue reconstruction that follows myofiber damage secondary to myotoxic injury that does not normally affect the tissue circulation and scaffold. The ablated tissue, in traumatology and free muscle grafts, is frequently replaced by scars. The final outcome is poor even after in situ myoblast seeding of the harvested muscle. The goal of this study was to identify protocols to reconstruct muscle tissue, even in such adverse environments. The authors applied a step-by-step approach to identify factors favoring the survival of autologous satellite cells and, thus, muscle regeneration. In a rat model of full-thickness rectus abdominis muscle ablation, autologous myoblasts were isolated from the explanted rectus abdominis and seeded in a homologous acellular matrix immediately after wall reconstruction (group 1, five animals). In group 2 (five animals), the ablated rectus abdominis was autografted in situ. In a third group of five rats, Marcaine was injected into both the autograft and the surrounding abdominal wall muscle. Three weeks after surgery, serial cross-sections of the reconstructed abdominal wall were stained with hematoxylin and eosin or embryonic myosin antibody, a well-characterized molecular marker of early myogenesis in development and regeneration. Percentages of the patch area covered by regenerated myofibers were determined by morphometry. When autologous myoblasts were seeded in a homologous acellular matrix, the only myofibers observed to regenerate were those along the border of the patch. Autografting of the middle third of the rectus abdominis muscle similarly resulted in scar formation. The few muscle cells in the graft core were scanty myoblasts that could be detected only by monoclonal embryonic myosin antibody. Although negative for myofiber regeneration, the results in both cases confirmed the mechanical patency of the patches with regard to abdominal organ support. Myofibers were successfully regenerated in the graft by injecting Marcaine into both the autograft and the surrounding muscles. Three weeks after surgery, the patch was paved with young, centrally nucleated myofibers intermixed with young myofibers and myotubes expressing embryonic myosin. The difference in percentage of patch area covered by regenerated myofibers in group 3 (Marcaine injection around the patch, 81.6 +/- 3.0 percent) (mean +/- SD) versus either group 1 (Myoblast-seeded acellular patch, 18.0 +/- 3.0 percent) or group 2 (Autograft, 25.8 +/- 7.0 percent) was statistically significant on independent t test analysis (p < 0.0001). Even an acellular matrix showed some myofiber regeneration after surrounding muscles had been injected with Marcaine. This is the first successful evidence of muscle reconstruction after full-thickness ablation of the middle third of the rectus abdominis. Muscle regeneration seems to be the result of successive waves of migration of angioblasts and then satellite cell-derived myoblasts from the muscles surrounding the patch. The results strongly suggest that vascularization of the scaffold and successive coordinate proliferation of the seeded cells are required for myoblasts to be able to migrate into the patch and differentiate up to myofiber stage. 相似文献
94.
95.
Development of biomarkers based on diet-dependent metabolic serotypes: characteristics of component-based models of metabolic serotypes 总被引:2,自引:0,他引:2
Paolucci U Vigneau-Callahan KE Shi H Matson WR Kristal BS 《Omics : a journal of integrative biology》2004,8(3):221-238
Our research seeks to identify a serum profile, or serotype, that reflects the systemic physiologic modifications resultant from dietary restriction (DR), in part such that this knowledge can be applied for biomarker studies. Direct comparison suggests that component-based classification algorithms consistently out-perform distance-based metrics for studies of nutritional modulation of metabolic serotype, but are subject to over-fitting concerns. Intercohort differences in the sera metabolome could partially obscure the effects of DR. Further analysis now shows that implementation of component-based approaches (also called projection methods) optimized for class separation and controlled for over-fitting have >97% accuracy for distinguishing sera from control or DR rats. DR's effect on the metabolome is shown to be robust across cohorts, but differs in males and females (although some metabolites are affected in both). We demonstrate the utility of projection-based methods for both sample and variable diagnostics, including identification of critical metabolites and samples that are atypical with respect to both class and variable models. Inclusion of non-statistically different variables enhances classification models. Variables that contribute to these models are sharply dependent on mathematical processing techniques; some variables that do not contribute under one paradigm are powerful under alternative mathematical paradigms. In practical terms, this information may find purpose in other endeavors, such as mechanistic studies of DR. Application of these approaches confirms the utility of megavariate data analysis techniques for optimal generation of biomarkers based on nutritional modulation of physiological processes. 相似文献
96.
Shi H Paolucci U Vigneau-Callahan KE Milbury PE Matson WR Kristal BS 《Omics : a journal of integrative biology》2004,8(3):197-208
Dietary restriction (DR)-induced changes in the serum metabolome may be biomarkers for physiological status (e.g., relative risk of developing age-related diseases such as cancer). Megavariate analysis (unsupervised hierarchical cluster analysis [HCA]; principal components analysis [PCA]) of serum metabolites reproducibly distinguish DR from ad libitum fed rats. Component-based approaches (i.e., PCA) consistently perform as well as or better than distance-based metrics (i.e., HCA). We therefore tested the following: (A) Do identified subsets of serum metabolites contain sufficient information to construct mathematical models of class membership (i.e., expert systems)? (B) Do component-based metrics out-perform distance-based metrics? Testing was conducted using KNN (k-nearest neighbors, supervised HCA) and SIMCA (soft independent modeling of class analogy, supervised PCA). Models were built with single cohorts, combined cohorts or mixed samples from previously studied cohorts as training sets. Both algorithms over-fit models based on single cohort training sets. KNN models had >85% accuracy within training/test sets, but were unstable (i.e., values of k could not be accurately set in advance). SIMCA models had 100% accuracy within all training sets, 89 % accuracy in test sets, did not appear to over-fit mixed cohort training sets, and did not require post-hoc modeling adjustments. These data indicate that (i) previously defined metabolites are robust enough to construct classification models (expert systems) with SIMCA that can predict unknowns by dietary category; (ii) component-based analyses outperformed distance-based metrics; (iii) use of over-fitting controls is essential; and (iv) subtle inter-cohort variability may be a critical issue for high data density biomarker studies that lack state markers. 相似文献
97.
Pasquale Linciano Luca Pinzi Silvia Belluti Ugo Chianese Rosaria Benedetti Davide Moi Lucia Altucci Silvia Franchini Carol Imbriano Claudia Sorbi Giulio Rastelli 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):2080
Histone deacetylase 6 (HDAC6) is an established drug target for cancer treatment. Inhibitors of HDAC6 based on a hydroxamic acid zinc binding group (ZBG) are often associated with undesirable side effects. Herein, we describe the identification of HDAC6 inhibitors based on a completely new 3-hydroxy-isoxazole ZBG. A series of derivatives decorated with different aromatic or heteroaromatic linkers, and various cap groups were synthesised and biologically tested. In vitro tests demonstrated that some compounds are able to inhibit HDAC6 with good potency, the best candidate reaching an IC50 of 700 nM. Such good potency obtained with a completely new ZBG make these compounds particularly attractive. The effect of the most active inhibitors on the acetylation levels of histone H3 and α- tubulin and their anti-proliferative activity of DU145 cells were also investigated. Docking studies were performed to evaluate the binding mode of these new derivatives and discuss structure-activity relationships. 相似文献
98.
The Protective Effect of Apocynin on Cyclosporine A‐Induced Hypertension and Nephrotoxicity in Rats
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99.
Ana Talamillo Leire Herboso Lucia Pirone Coralia Pérez Monika González Jonatan Sánchez Ugo Mayor Fernando Lopitz-Otsoa Manuel S. Rodriguez James D. Sutherland Rosa Barrio 《PLoS genetics》2013,9(4)
SUMOylation participates in ecdysteroid biosynthesis at the onset of metamorphosis in Drosophila melanogaster. Silencing the Drosophila SUMO homologue smt3 in the prothoracic gland leads to reduced lipid content, low ecdysone titers, and a block in the larval–pupal transition. Here we show that the SR-BI family of Scavenger Receptors mediates SUMO functions. Reduced levels of Snmp1 compromise lipid uptake in the prothoracic gland. In addition, overexpression of Snmp1 is able to recover lipid droplet levels in the smt3 knockdown prothoracic gland cells. Snmp1 expression depends on Ftz-f1 (an NR5A-type orphan nuclear receptor), the expression of which, in turn, depends on SUMO. Furthermore, we show by in vitro and in vivo experiments that Ftz-f1 is SUMOylated. RNAi–mediated knockdown of ftz-f1 phenocopies that of smt3 at the larval to pupal transition, thus Ftz-f1 is an interesting candidate to mediate some of the functions of SUMO at the onset of metamorphosis. Additionally, we demonstrate that the role of SUMOylation, Ftz-f1, and the Scavenger Receptors in lipid capture and mobilization is conserved in other steroidogenic tissues such as the follicle cells of the ovary. smt3 knockdown, as well as ftz-f1 or Scavenger knockdown, depleted the lipid content of the follicle cells, which could be rescued by Snmp1 overexpression. Therefore, our data provide new insights into the regulation of metamorphosis via lipid homeostasis, showing that Drosophila Smt3, Ftz-f1, and SR-BIs are part of a general mechanism for uptake of lipids such as cholesterol, required during development in steroidogenic tissues. 相似文献
100.
Ugo Cenci Malika Chabi Mathieu Ducatez Catherine Tirtiaux Jennifer Nirmal-Raj Yoshinori Utsumi Daiki Kobayashi Satoshi Sasaki Eiji Suzuki Yasunori Nakamura Jean-Luc Putaux Xavier Roussel Amandine Durand-Terrasson Debashish Bhattacharya Anne-Sophie Vercoutter-Edouart Emmanuel Maes Maria Cecilia Arias Monica Palcic Lyann Sim Steven G. Ball Christophe Colleoni 《The Plant cell》2013,25(10):3961-3975
Starch, unlike hydrosoluble glycogen particles, aggregates into insoluble, semicrystalline granules. In photosynthetic eukaryotes, the transition to starch accumulation occurred after plastid endosymbiosis from a preexisting cytosolic host glycogen metabolism network. This involved the recruitment of a debranching enzyme of chlamydial pathogen origin. The latter is thought to be responsible for removing misplaced branches that would otherwise yield a water-soluble polysaccharide. We now report the implication of starch debranching enzyme in the aggregation of semicrystalline granules of single-cell cyanobacteria that accumulate both glycogen and starch-like polymers. We show that an enzyme of analogous nature to the plant debranching enzyme but of a different bacterial origin was recruited for the same purpose in these organisms. Remarkably, both the plant and cyanobacterial enzymes have evolved through convergent evolution, showing novel yet identical substrate specificities from a preexisting enzyme that originally displayed the much narrower substrate preferences required for glycogen catabolism. 相似文献