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21.
Elucidating pathways that regulate cytokine production in the context of autoimmune disease will likely lead to the development of novel therapeutics. Herein, we review data suggesting that microRNAs (miRs) represent one such level of regulatory activity, with particular emphasis on the pathogenesis of rheumatoid arthritis (RA). A series of miRs have been identified to be dysregulated in cell subsets within the articular compartment of patients with RA. These have a critical role in regulating cartilage-invading phenotype of RA synovial fibroblasts. More recently, several studies suggest that miRs also regulate leukocyte activation and cytokine production that in turn contribute to the immunologic component of effector synovial pathology. Together, these observations open an exciting new vista of understanding and therapeutic opportunity for this difficult and common disease. 相似文献
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José L.G. Galindo Mariola Macías José M.G. Molinillo Alba Muñoz-Suano Ascensión Torres Rosa M. Varela Francisco García-Cozar Francisco A. Macías 《Bioorganic & medicinal chemistry》2012,20(22):6662-6668
Bioactive natural products are a potential source of new pharmaceuticals since they offer new modes of action and more specific activities. The use of derivatization also enables the optimal structure for their biological activity to be determined. In this study several epoxycurcuphenol derivatives were synthesized. The substitution pattern on the aromatic and oxirane rings was varied along with that at the benzylic position and the length of the side chain was altered. These changes were made in order to gain a deeper understanding of the structural requirements for activity. The biological activities of these compounds were evaluated on the human leukemia cell line Jurkat using an antiproliferative assay. The activity results and structural requirements are discussed. 相似文献
24.
McKimmie CS Fraser AR Hansell C Gutiérrez L Philipsen S Connell L Rot A Kurowska-Stolarska M Carreno P Pruenster M Chu CC Lombardi G Halsey C McInnes IB Liew FY Nibbs RJ Graham GJ 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(5):3353-3363
D6 scavenges inflammatory chemokines and is essential for the regulation of inflammatory and immune responses. Mechanisms explaining the cellular basis for D6 function have been based on D6 expression by lymphatic endothelial cells. In this study, we demonstrate that functional D6 is also expressed by murine and human hemopoietic cells and that this expression can be regulated by pro- and anti-inflammatory agents. D6 expression was highest in B cells and dendritic cells (DCs). In myeloid cells, LPS down-regulated expression, while TGF-beta up-regulated expression. Activation of T cells with anti-CD3 and soluble CD28 up-regulated mRNA expression 20-fold, while maturation of human macrophage and megakaryocyte precursors also up-regulated D6 expression. Competition assays demonstrated that chemokine uptake was D6 dependent in human leukocytes, whereas mouse D6-null cells failed to uptake and clear inflammatory chemokines. Furthermore, we present evidence indicating that D6 expression is GATA1 dependent, thus explaining D6 expression in myeloid progenitor cells, mast cells, megakaryocytes, and DCs. We propose a model for D6 function in which leukocytes, within inflamed sites, activate D6 expression and thus trigger resolution of inflammatory responses. Our data on D6 expression by circulating DCs and B cells also suggest alternative roles for D6, perhaps in the coordination of innate and adaptive immune responses. These data therefore alter our models of in vivo D6 function and suggest possible discrete, and novel, roles for D6 on lymphatic endothelial cells and leukocytes. 相似文献
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Coombes BK Wickham ME Mascarenhas M Gruenheid S Finlay BB Karmali MA 《Applied and environmental microbiology》2008,74(7):2153-2160
Shiga toxin-producing Escherichia coli (STEC) strains are commensal bacteria in cattle with high potential for environmental and zoonotic transmission to humans. Although O157:H7 is the most common STEC serotype, there is growing concern over the emergence of more than 200 highly virulent non-O157 STEC serotypes that are globally distributed, several of which are associated with outbreaks and/or severe human illness such as hemolytic-uremic syndrome (HUS) and hemorrhagic colitis. At present, the underlying genetic basis of virulence potential in non-O157 STEC is unknown, although horizontal gene transfer and the acquisition of new pathogenicity islands are an expected origin. We used seropathotype classification as a framework to identify genetic elements that distinguish non-O157 STEC strains posing a serious risk to humans from STEC strains that are not associated with severe and epidemic disease. We report the identification of three genomic islands encoding non-LEE effector (nle) genes and 14 individual nle genes in non-O157 STEC strains that correlate independently with outbreak and HUS potential in humans. The implications for transmissible zoonotic spread and public health are discussed. These results and methods offer a molecular risk assessment strategy to rapidly recognize and respond to non-O157 STEC strains from environmental and animal sources that might pose serious public health risks to humans. 相似文献
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Kowalik-Jankowska T Biega L Kuczer M Konopińska D 《Journal of inorganic biochemistry》2008,102(8):1615-1622
The stoichiometry, stability constants and solution structure of the complexes formed in the reaction of copper(II) with hexapeptide NPTNLH, i.e. the Neobelliera Bullata Trypsin Modulating Oostatic Factor (Neb-TMOF), and its analogues DPTNLH, Ac-NPTNLH and Ac-DPTNLH have been determined by potentiometric, UV-visible, CD and EPR spectroscopic methods. Upon raising pH for Ac-NPTNLH and Ac-DPTNLH peptides, copper(II) coordination starts from the imidazole nitrogen of the His6; afterwards three deprotonated amide nitrogens are progressively involved in metal ions coordination. In a wide pH range of 4.5-8.5 for the NPTNLH and DPTNLH ligands the CuL complex dominates with the imidazole nitrogen of His6 coordinated to form a macrochelate. The N-terminal amino group of the NPTNLH and DPTNLH peptides takes part in the coordination of the metal ion in the CuL, CuH−1L and CuH−2L complexes. However, at pH above 9 the CuH−3L complex with the {NIm, 3N−} coordination mode is formed. For the CuH−2L complex the spectroscopic data clearly indicate the 4N {NH2, CO or COO−, 2N−, NIm} bonding mode with the axial coordination of the N-terminal amine group to the metal ion. 相似文献
28.
This article reviews the treatment options of the twin-twin transfusion syndrome (TTTS). No single therapy is associated with a uniformly improved outcome for the involved twins and success is primarily related to gestational age and severity at diagnosis. Treatment options for severe cases include digitalization, ligation of the umbilical cord, serial amniocenteses, septostomy, laser occlusion of placental vessels, and selective feticide. These modalities are associated with significant risks of complications, and variable results of fetal morbidity and mortality. Therefore, they should be considered when risks of withholding treatment clearly outweigh those associated with intervention. 相似文献
29.
Mariola Gepfert Jakub Jarosz Grzegorz Wojdala Michal Krzysztofik Yuri Campos Aleksandra Filip-Stachnik Maciej Kostrzewa Dawid Gawel Agnieszka Szkudlarek Piotr Godlewski Petr Stastny Michal Wilk 《Biology of sport / Institute of Sport》2021,38(4):653
The main goal of the present study was to evaluate the acute effects of blood flow restriction (BFR) at 70% of full arterial occlusion pressure on strength-endurance performance during the bench press exercise. The study included 14 strength-trained male subjects (age = 25.6 ± 4.1 years; body mass = 81.7 ± 10.8 kg; bench press 1 repetition maximum (1RM) = 130.0 ± 22.1 kg), experienced in resistance training (3.9 ± 2.4 years). During the experimental sessions in a randomized crossover design, the subjects performed three sets of the bench press at 80% 1RM performed to failure with two different conditions: without BFR (CON); and with BFR (BFR). Friedman’s test showed significant differences between BFR and CON conditions for the number of repetitions performed (p < 0.001); for peak bar velocity (p < 0.001) and for mean bar velocity (p < 0.001). The pairwise comparisons showed a significant decrease for peak bar velocity and mean bar velocity in individual Set 1 for BFR when compared to CON conditions (p = 0.01 for both). The two-way repeated measures ANOVA showed a significant main effect for the time under tension (p = 0.02). A post-hoc comparisons for the main effect showed a significant increase in time under tension for BFR when compared to CON (p = 0.02). The results of the presented study indicate that BFR used during strength-endurance exercise generally does not decrease the level of endurance performance, while it causes a drop in bar velocity. 相似文献
30.
Muhammad Emaduddin Mariola J Edelmann Benedikt M Kessler Stephan M Feller 《Cell communication and signaling : CCS》2008,6(1):1-11