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71.
Fibroblast dynamics as an in vitro screening platform for anti‐fibrotic drugs in primary myelofibrosis
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Ciprian Tomuleasa MD PhD Sonia Selicean MD Grigore Gafencu MD Bobe Petrushev MD Laura Pop PhD Cristian Berce PhD Anca Jurj PhD Adrian Trifa MD PhD Ana‐Maria Rosu MD Sergiu Pasca MD Lorand Magdo MD Mihnea Zdrenghea MD PhD Delia Dima MD PhD Alina Tanase MD PhD Ioana Frinc MD Anca Bojan MD Ioana Berindan‐Neagoe PhD Gabriel Ghiaur MD PhD Stefan O. Ciurea MD 《Journal of cellular physiology》2018,233(1):422-433
Although the cause for bone marrow fibrosis in patients with myelofibrosis remains controversial, it has been hypothesized that it is caused by extensive fibroblast proliferation under the influence of cytokines generated by the malignant megakaryocytes. Moreover, there is no known drug therapy which could reverse the process. We studied the fibroblasts in a novel system using the hanging drop method, evaluated whether the fibroblasts obtain from patients are part of the malignant clone of not and, using this system, we screen a large library of FDA‐approved drugs to identify potential drugs candidates that might be useful in the treatment of this disease, specifically which would inhibit fibroblast proliferation and the development of bone marrow fibrosis. We have found that the BM fibroblasts are not part of the malignant clone, as previously suspected and two immunosuppressive medications—cyclosporine and mycophenolate mophetil, as most potent suppressors of the fibroblast collagen production thus potentially inhibitors of bone marrow fibrosis production in myelofibrosis. 相似文献
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74.
A nuclear mutant of Arabidopsis thaliana selected for enhanced sensitivity to light-chill stress is altered in PSII electron transport activity 总被引:1,自引:0,他引:1
Delia Tarantino Alberto Vianelli Luisa Carraro Carlo Soave 《Physiologia plantarum》1999,107(3):361-371
Chilling in the light imposes a considerable level of stress on the photosynthetic apparatus, resulting in a decrease of photosystem II activity and the quenching of maximum and variable fluorescence. We selected in a fah - 1 mutagenized population of Arabidopsis thaliana , which permits a direct visible evaluation of the intensity of chlorophyll (Chl) fluorescence, a monogenic recessive nuclear mutant hypersensitive to photoinhibition induced by light and cold. The major phenotypic trait of the mutant is the appearance of chlorotic areas on developed leaves. Photochemical analyses indicate that the mutant is hypersensitive to photoinhibition in excess light in the cold but also at room temperature. The susceptibility to photoinhibition is a consequence of perturbations in photochemistry already present in unstressed plants. Such perturbations result in a greater fraction of the primary acceptor QA remaining in the reduced state even at low light fluxes. From estimates of the number of total and functional PSII units and measurements of PSII quantum yield and QA − reoxidation kinetics, the basic lesion of the mutant seems restricted to PSII photochemistry likely affecting the rate of electron transport from QA − to QB . 相似文献
75.
V. Calvente D. Benuzzi M. I. S. de Tosetti 《International biodeterioration & biodegradation》1999,43(4):M254
Rhodotorulic acid produced by Rhodotorula glutinis strains improved the biological control of blue rot caused by Penicillium expansum in harvested apples. The production of the siderophore was closely associated with the iron concentration in the medium. Thus, very low additions of the metal reduced the siderophore production considerably. The antagonistic effect of R. glutinis and rhodotorulic acid was studied by using in vitro and in vivo assays. In the in vitro assays, rhodotorulic acid reduced the growth of P. expansum, whereas the chelate (rhodotorulic acid plus iron) did not. Siderophore antagonism was then related to competition for iron. In biocontrol assays on apple wounds, the blue mold was more effectively controlled by the antagonistic agent plus siderophore than by the antagonistic agent alone. The disease incidence (DI: percentage of treated wounds that developed rot) was 34% when apples were protected by R. glutinis alone, whereas it was 6% when the fruits were protected by R. glutinis plus rhodotorulic acid. 相似文献
76.
Pietro Amodeo Fred Naider Delia Picone Teodorico Tancredi Piero A. Temussi 《Journal of peptide science》1998,4(4):253-265
Conformational studies of enkephalins are hampered by their high flexibility which leads to mixtures of quasi-isoenergetic conformers in solution and makes NOEs very difficult to detect in NMR spectra. In order to improve the quality of the NMR data, Leu–enkephalin was synthesized with 15N-labelled uniformly on all amide nitrogens and examined in a viscous solvent medium at low temperature. HMQC NOESY spectra of the labelled Leu–enkephalin in a DMSOd6/H2O mixture at 275 K do show numerous NOEs, but these are not consistent with a single conformer and are only sufficient to describe the conformational state as a mixture of several conformers. Here a different approach to the structure–activity relationships of enkephalins is presented: it is possible to analyse the NMR data in terms of limiting canonical structures (i.e. β- and γ-turns) and finally to select only those consistent with the requirements of δ selective agonists and antagonists. This strategy results in the prediction of a family of conformers that may be useful in the design of new δ selective opioid peptides. © 1998 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
77.
Florin G. Horhat Fuat Gundogdu Laurentiu V. David Eugen S. Boia Laurentiu Pirtea Razvan Horhat Alexandru Cucui-Cozma Ioana Ciuca Mircea Diaconu Razvan Nitu Monica Licker Delia I. Horhat Alexandru F. Rogobete Marius L. Moise Calin Tataru 《Biochemical genetics》2017,55(3):204-211
A high percentage of critical patients are found to develop acute respiratory distress syndrome (ARDS). Several studies have reported high mortality rates in these cases which are most frequently associated with multiple organ dysfunctions syndrome. Lately, many efforts have been made to evaluate and monitor ARDS in critical patients. In this regard, the assessment of genetic polymorphisms responsible for developing ARDS present as a challenge and are considered future biomarkers. Early detection of the specific polymorphic gene responsible for ARDS in critically ill patients can prove to be a useful tool in the future, able to help decrease the mortality rates in these cases. Moreover, identifying the genetic polymorphism in these patients can help in the implementation of a personalized intensive therapy scheme for every type of patient, based on its genotype. 相似文献
78.
Oppedisano F Fanello D Calvani M Indiveri C 《Journal of biochemical and molecular toxicology》2008,22(1):8-14
The interaction of mildronate [3-(2,2,2-trimethylhydrazine) propionate] with the purified mitochondrial carnitine/acylcarnitine transporter reconstituted in liposomes has been studied. Mildronate, externally added to the proteoliposomes, strongly inhibited the carnitine/carnitine antiport catalyzed by the reconstituted transporter with an IC(50) of 560 muM. A kinetic analysis revealed that the inhibition is completely competitive, that is, mildronate interacts with the substrate-binding site. The half-saturation constant of the transporter for external mildronate (K(i)) is 530 muM. Carnitine/mildronate antiport has been measured as [(3)H]carnitine uptake into proteoliposomes containing internal mildronate or as [(3)H]carnitine efflux from proteoliposomes in the presence of external mildronate, indicating that mildronate is transported by the carnitine/acylcarnitine transporter and that the inhibition observed was due to the transport of mildronate in the place of carnitine. The intraliposomal half-saturation constant for mildronate transport (K(m)) has been determined. Its value, 18 mM, is much higher than the external half-saturation constant (K(i)) in agreement with the asymmetric properties of the transporter. In vivo, the antiport reaction between cytosolic (administered) mildronate and matrix carnitine may cause intramitochondrial carnitine depletion. This effect, together with the inhibition of the physiological transport, will lead to impairment of fatty acid utilization. 相似文献
79.
Tabrizi MA Baraldi PG Preti D Romagnoli R Saponaro G Baraldi S Moorman AR Zaid AN Varani K Borea PA 《Bioorganic & medicinal chemistry》2008,16(5):2419-2430
A new series of 1,3-dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives has been identified as potent A(2B) adenosine receptor antagonists. The products have been evaluated for their binding affinities for the human A(2B), A(1), A(2A), and A(3) adenosine receptors. N-(4-chloro-phenyl)-2-[3-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-5-methyl-pyrazol-1-yl] (11c) showed a high affinity for the human A(2B) adenosine receptor K(i)=7nM and good selectivity (A(1), A(2A), A(3)/A(2B)>140). Synthesis and SAR of this novel class of compounds is presented herein. 相似文献
80.
Nicole Vlahovich Anthony J. Kee Chris Van der Poel Emma Kettle Delia Hernandez-Deviez Christine Lucas Gordon S. Lynch Robert G. Parton Peter W. Gunning Edna C. Hardeman 《Molecular biology of the cell》2009,20(1):400-409
The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation–contraction coupling in skeletal muscle. 相似文献