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Malgorzata Kloc Ahmed Uosef Jacek Z. Kubiak Rafik Mark Ghobrial 《International journal of molecular sciences》2021,22(1)
The development, progression, or stabilization of the atherosclerotic plaque depends on the pro-inflammatory and anti-inflammatory macrophages. The influx of the macrophages and the regulation of macrophage phenotype, inflammatory or anti-inflammatory, are controlled by the small GTPase RhoA and its downstream effectors. Therefore, macrophages and the components of the RhoA pathway are attractive targets for anti-atherosclerotic therapies, which would inhibit macrophage influx and inflammatory phenotype, maintain an anti-inflammatory environment, and promote tissue remodeling and repair. Here, we discuss the recent findings on the role of macrophages and RhoA pathway in the atherosclerotic plaque formation and resolution and the novel therapeutic approaches. 相似文献
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Malgorzata Kardynska Jaroslaw Smieja Pawel Paszek Krzysztof Puszynski 《International journal of molecular sciences》2022,23(12)
Mathematical modeling of signaling pathways and regulatory networks has been supporting experimental research for some time now. Sensitivity analysis, aimed at finding model parameters whose changes yield significantly altered cellular responses, is an important part of modeling work. However, sensitivity methods are often directly transplanted from analysis of technical systems, and thus, they may not serve the purposes of analysis of biological systems. This paper presents a novel sensitivity analysis method that is particularly suited to the task of searching for potential molecular drug targets in signaling pathways. Using two sample models of pathways, p53/Mdm2 regulatory module and IFN--induced JAK/STAT signaling pathway, we show that the method leads to biologically relevant conclusions, identifying processes suitable for targeted pharmacological inhibition, represented by the reduction of kinetic parameter values. That, in turn, facilitates subsequent search for active drug components. 相似文献
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Frederik J. Hansen Zhiyuan Wu Paul David Anke Mittelstdt Anne Jacobsen Malgorzata J. Podolska Kenia Ubieta Maximilian Brunner Dina Kouhestani Izabela Swierzy Lotta Roßdeutsch Bettina Klsch Isabella Kutschick Susanne Merkel Axel Denz Klaus Weber Carol Geppert Robert Grützmann Alan Bnard Georg F. Weber 《International journal of molecular sciences》2022,23(9)
Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5′-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73+ B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73+ B-cells. Finally, neoadjuvant therapy correlated with reduced CD73+ B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73+ B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options. 相似文献
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Tom Schreiner Lisa Allnoch Georg Beythien Katarzyna Marek Kathrin Becker Dirk Schaudien Stephanie Stanelle-Bertram Berfin Schaumburg Nancy Mounogou Kouassi Sebastian Beck Martin Zickler Gülsah Gabriel Wolfgang Baumgrtner Federico Armando Malgorzata Ciurkiewicz 《International journal of molecular sciences》2022,23(9)
Similar to many other respiratory viruses, SARS-CoV-2 targets the ciliated cells of the respiratory epithelium and compromises mucociliary clearance, thereby facilitating spread to the lungs and paving the way for secondary infections. A detailed understanding of mechanism involved in ciliary loss and subsequent regeneration is crucial to assess the possible long-term consequences of COVID-19. The aim of this study was to characterize the sequence of histological and ultrastructural changes observed in the ciliated epithelium during and after SARS-CoV-2 infection in the golden Syrian hamster model. We show that acute infection induces a severe, transient loss of cilia, which is, at least in part, caused by cilia internalization. Internalized cilia colocalize with membrane invaginations, facilitating virus entry into the cell. Infection also results in a progressive decline in cells expressing the regulator of ciliogenesis FOXJ1, which persists beyond virus clearance and the termination of inflammatory changes. Ciliary loss triggers the mobilization of p73+ and CK14+ basal cells, which ceases after regeneration of the cilia. Although ciliation is restored after two weeks despite the lack of FOXJ1, an increased frequency of cilia with ultrastructural alterations indicative of secondary ciliary dyskinesia is observed. In summary, the work provides new insights into SARS-CoV-2 pathogenesis and expands our understanding of virally induced damage to defense mechanisms in the conducting airways. 相似文献
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Viscosity is one of the most important attributes of rye-based products related to some health benefits. To identify the factors affecting arabinoxylan-dependent extract viscosity (AX-EV) of rye bread, the structural features of water-extractable arabinoxylans (WE-AXs) and their ammonium sulphate precipitated subfractions were investigated in breads with varied viscosities. Also, an endoxylanase activity in the starting flours was examined. The HPSEC-RI profiles revealed the higher extent of AX depolymerisation in whole-meal bread (WMB) when compared to that in endosperm bread (EB), resulting in its lower AX-EV. This was mostly related to lower molecular weight of the parent WE-AX fraction with distinctly lower proportion of 2-Xylp in the chain. The AX-EV of rye bread decreased with decreasing proportion of AX-I, the major subfraction with 3-Xylp as only branching site. The endoxylanase activity was at least two times lower in endosperm flour than that in WM and negatively correlated with the AX-EV of WMB. The importance of densely substituted AX subfractions with exclusively 2-Xylp and 2,3-Xylp branches, protecting the AX-I from enzymic degradation during bread-making, has been evidenced. 相似文献
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Malgorzata Młynarczyk Malgorzata Sznitowska Dorota Watrobska-Swietlikowska 《Drug development and industrial pharmacy》2013,39(4):355-362
Antimicrobial efficacy of methyl and propylparaben combination as potential preservatives for submicron emulsions, and the effect of oil and lecithin concentration on the microbial growth were investigated. Parabens were ineffective in standard or doubled concentrations as per pharmacopoeial criteria. Poor growth inhibition and multiplication of reference strains point to protective and growth properties of submicron emulsions. No correlation was observed between oil/lecithin ratio and efficacy of parabens; partitioning of the latter into the oily phase and lipophilic domains could be the reason for such effect. Further studies are necessary to establish a stable and safe composition of such formulations. 相似文献
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Renata Rybakiewicz David Djurado Hubert Cybulski Ewelina Dobrzynska Irena Kulszewicz-Bajer Damien Boudinet Jean-Marie Verilhac Malgorzata Zagorska Adam Pron 《Synthetic Metals》2011,161(15-16):1600-1610
New solution processable organic semiconductors, consisting of pyrromelitic, naphthalene or perylene bisimide core and triarylamine N-substituents, have been synthesized. All three compounds are electrochemically active and undergo quasi-reversible oxidation and reduction as evidenced by cyclic voltammetry investigations. The oxidation process involves the transformation of the triarylamine substituents into radical cations as proven spectroscopically and spectroelectrochemically. The reduction process occurs at the arylene bisimide core leading to the formation of a radical anion and eventually a dianion in the second step. These findings are in perfect agreement with the DFT calculations which show that in the synthesized molecules the HOMO orbital is located on the triarylamine moiety whereas the LUMO one on the bisimide core. In all molecules studied the electrochemically determined ionization potential (IP) is slightly higher than 5.0 eV whereas in naphthalene and perylene derivatives the electron affinity (EA) is close to ?3.9 eV. These values fulfill the requirements for n-type (electron) semiconductors in air operating n-channel field effect transistors (FETs) as well as for p-type (hole) conductors in p-channel FETs. To verify whether the newly synthesized compounds exhibit the expected electrical transport properties all organic (CYTOP dielectric) test transistors were fabricated. All three semiconductors showed no field effect in the n-channel configuration. To the contrary, they could be used in p-channel FETs showing, in the saturation regime, the hole mobility approaching 10?4 cm2 V?1 s?1 – the value which slightly exceeds that measured for low molecular weight, amorphous triarylamine semiconductors. 相似文献