Search results for "22"
showing 10 items of 13984 documents
Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
2020
Abstract Background Exposure to ionizing radiation induces complex stress responses in cells, which can lead to adverse health effects such as cancer. Although a variety of studies investigated gene expression and affected pathways in human fibroblasts after exposure to ionizing radiation, the understanding of underlying mechanisms and biological effects is still incomplete due to different experimental settings and small sample sizes. Therefore, this study aims to identify the time point with the highest number of differentially expressed genes and corresponding pathways in primary human fibroblasts after irradiation at two preselected time points. Methods Fibroblasts from skin biopsies of…
MicroRNA-22 Controls Aberrant Neurogenesis and Changes in Neuronal Morphology After Status Epilepticus
2018
Prolonged seizures (status epilepticus, SE) may drive hippocampal dysfunction and epileptogenesis, at least partly, through an elevation in neurogenesis, dysregulation of migration and aberrant dendritic arborization of newly-formed neurons. MicroRNA-22 was recently found to protect against the development of epileptic foci, but the mechanisms remain incompletely understood. Here, we investigated the contribution of microRNA-22 to SE-induced aberrant adult neurogenesis. SE was induced by intraamygdala microinjection of kainic acid (KA) to model unilateral hippocampal neuropathology in mice. MicroRNA-22 expression was suppressed using specific oligonucleotide inhibitors (antagomir-22) and ne…
Keratinocyte-derived IκBζ drives psoriasis and associated systemic inflammation.
2019
The transcriptional activator IκBζ is a key regulator of psoriasis, but which cells mediate its pathogenic effect remains unknown. Here we found that IκBζ expression in keratinocytes triggers not only skin lesions but also systemic inflammation in mouse psoriasis models. Specific depletion of IκBζ in keratinocytes was sufficient to suppress the induction of imiquimod- or IL-36–mediated psoriasis. Moreover, IκBζ ablation in keratinocytes prevented the onset of psoriatic lesions and systemic inflammation in keratinocyte-specific IL-17A–transgenic mice. Mechanistically, this psoriasis protection was mediated by IκBζ deficiency in keratinocytes abrogating the induction of specific proinflammato…
CD1A-positive cells and HSP60 (HSPD1) levels in keratoacanthoma and squamous cell carcinoma.
2015
CD1a is involved in presentation to the immune system of lipid antigen derived from tumor cells with subsequent T cell activation. Hsp60 is a molecular chaperone implicated in carcinogenesis by, for instance, modulating the immune reaction against the tumor. We have previously postulated a synergism between CD1a and Hsp60 as a key factor in the activation of an effective antitumor immune response in squamous epithelia. Keratoacantomas (KAs) are benign tumors that however can transform into squamous cell carcinomas (SCCs), but the reasons for this malignization are unknown. In a previous study, we found that CD1a-positive cells are significantly more numerous in KA than in SCC. In this study…
Double-exponential kinetics of binding and redistribution of the fluorescent dyes in cell membranes witness for the existence of lipid microdomains.
2018
Abstract New technique of detecting lateral heterogeneity of the plasma membrane of living cells by means of membrane-binding fluorescent dyes is proposed. The kinetics of dye incorporation into the membrane or its lateral diffusion inside the membrane is measured and decomposed into exponential components by means of the Maximum Entropy Method. Two distinct exponential components are obtained consistently in all cases for several fluorescent dyes, two different cell lines and in different types of experiments including spectroscopy, flow cytometry and fluorescence recovery after photobleaching. These components are attributed to the liquid-ordered and disordered phases in the plasma membra…
Global Assessment of the Activity of Tigecycline against Multidrug-Resistant Gram-Negative Pathogens between 2004 and 2014 as Part of the Tigecycline…
2017
Multidrug resistance among bacterial pathogens is an ongoing global problem and renders antimicrobial agents ineffective at treating bacterial infections. In the health care setting, infections caused by multidrug-resistant (MDR) Gram-negative bacteria can cause increased mortality, longer hospital stays, and higher treatments costs. The aim of the Tigecycline Evaluation and Surveillance Trial (TEST) is to assess the in vitro antimicrobial activities of tigecycline and other contemporary agents against clinically relevant pathogens. This paper presents antimicrobial activity data from the TEST study between 2004 and 2014 and examines global rates of MDR Gram-negative isolates, including Aci…
A selective inhibitor of the Polo-box domain of Polo-like kinase 1 identified by virtual screening
2018
Graphical abstract
Anticancer potential of novel α,β-unsaturated γ-lactam derivatives targeting the PI3K/AKT signaling pathway.
2021
Abstract Six recently synthesized alkyl (Z)-2-(2-oxopyrrolidin-3-ylidene)acetates were evaluated for their potential as cytotoxic and anticancer agents. All compounds were tested in the ERα positive MCF-7, triple negative MDA-MB-231, and Her2+ SKBR-3 breast cancer cell lines. The most lipophilic derivatives, bearing the 4-isopropylphenyl (2) or 4-tert-butylphenyl (3) group at the γ-lactam nitrogen, proved to be cytotoxic against all the cancer cell lines tested (IC50 values ranging from 18 to 63 μM), exerting their greatest activity in SKBR-3 cells, with IC50 values of 33 and 18 μM, respectively. Biological studies showed that the cytotoxic effects of 2 and 3 are accompanied by apoptotic de…
Dermal CD207-Negative Migratory Dendritic Cells Are Fully Competent to Prime Protective, Skin Homing Cytotoxic T-Lymphocyte Responses
2018
Dendritic cells (DCs) are important inducers and regulators of T-cell responses. They are able to activate and modulate the differentiation of CD4+ and CD8+ T cells. In the skin, there are at least five phenotypically distinct DC subpopulations that can be distinguished by differential expression of the cell surface markers CD207, CD103, and CD11b. Previous studies have suggested that dermal CD11b−CD207+ conventional type 1 DCs are indispensable for the priming of a skin homing cytotoxic T-lymphocyte response. However, conventional type 1 DCs are also the only skin DC subset capable of cross-presenting exogenous antigens on major histocompatibility complex class I. Thus, it remained unclear…
Langerhans Cells Suppress CD8+ T Cells In Situ during Mucocutaneous Acute Graft-Versus-Host Disease
2021
Acute graft-versus-host disease (aGVHD) induced by allogenic hematopoietic stem cell transplantation is an immunological disorder in which donor lymphocytes attack recipient organs. It has been proven that recipient nonhematopoietic tissue cells, such as keratinocytes, are sufficient as immunological targets for allogenic donor T cells, whereas Langerhans cells (LCs) are potent professional hematopoietic antigen-presenting cells existing in the target epidermis and eliminated during the early phase of mucocutaneous aGVHD. Moreover, LCs have been reported to negatively regulate various types of immune responses. Here, we present data showing that initial depletion of recipient LCs exacerbate…