Search results for "factor"
showing 10 items of 17757 documents
Histidine tracts in human transcription factors: insight into metal ion coordination ability
2017
Consecutive histidine repeats are chosen both by nature and by molecular biologists due to their high affinity towards metal ions. Screening of the human genome showed that transcription factors are extremely rich in His tracts. In this work, we examine two of such His-rich regions from forkhead box and MAFA proteins—MB3 (contains 18 His) and MB6 (with 21 His residues), focusing on the affinity and binding modes of Cu2+ and Zn2+ towards the two His-rich regions. In the case of Zn2+ species, the availability of imidazole nitrogen donors enhances metal complex stability. Interestingly, an opposite tendency is observed for Cu2+ complexes at above physiological pH, in which amide nitrogens part…
New 3-Aryl-2-(2-Thienyl)acrylonitriles with High Activity against Hepatoma Cells
2021
New 2-(thien-2-yl)-acrylonitriles with putative kinase inhibitory activity were prepared and tested for their antineoplastic efficacy in hepatoma models. Four out of the 14 derivatives were shown to inhibit hepatoma cell proliferation at (sub-)micromolar concentrations with IC50 values below that of the clinically relevant multikinase inhibitor sorafenib, which served as a reference. Colony formation assays as well as primary in vivo examinations of hepatoma tumors grown on the chorioallantoic membrane of fertilized chicken eggs (CAM assay) confirmed the excellent antineoplastic efficacy of the new derivatives. Their mode of action included an induction of apoptotic capsase-3 activity, whil…
The role of extracellular calcium in bone metastasis
2016
AbstractThis review summarizes the role of extracellular calcium, as found present in the bone tissue, in the process of bone metastasis.
Immunosenescence and its hallmarks: How to oppose aging strategically? A review of potential options for therapeutic intervention
2019
Aging is accompanied by remodeling of the immune system. With time, this leads to a decline in immune efficacy, resulting in increased vulnerability to infectious diseases, diminished responses to vaccination, and a susceptibility to age-related inflammatory diseases. An age-associated immune alteration, extensively reported in previous studies, is the reduction in the number of peripheral blood naive cells, with a relative increase in the frequency of memory cells. These two alterations, together with inflamm-aging, are considered the hallmarks of immunosenescence. Because aging is a plastic process, it is influenced by both nutritional and pharmacological interventions. Therefore, the rol…
Fungal Deoxynivalenol-Induced Enterocyte Distress Is Attenuated by Adulterated Adlay: In Vitro Evidences for Mucoactive Counteraction
2018
Adlay is a cereal crop that has long been used as traditional herbal medicine and as a highly nourishing food. However, deoxynivalenol (DON), the most prevalent trichothecene mycotoxin worldwide, frequently spoils grains, including adlay, via fungal infection. On the basis of an assumption that the actions of DON in the gut could be modified by adlay consumption, we simulated the impacts of co-exposure in enterocytes and investigated the effectiveness of treatment with adlay for reducing the risk of DON-induced inflammation and epithelia barrier injury. In particular, adlay suppressed DON-induced pro-inflammatory signals such as mitogen-activated kinase transduction and the epidermal growth…
Structure–Activity Relationship of Plesiomonas shigelloides Lipid A to the Production of TNF-α, IL-1β, and IL-6 by Human and Murine Macrophages
2017
Plesiomonas shigelloides is a Gram-negative bacterium that is associated with diarrheal disease in humans. Lipopolysaccharide (LPS) is the main surface antigen and virulence factor of this bacterium. The lipid A (LA) moiety of LPS is the main region recognized by target cells of immune system. Here, we evaluated the biological activities of P. shigelloides LA for their abilities to induce the productions of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) by human and murine macrophages [THP-1 macrophages and immortalized murine bone marrow-derived macrophages (iBMDM)]. Four native P. shigelloides LA preparations differing in their phosphoethanolamine (PEtn) substitution, length, number, …
Anti-Tumor Necrosis Factor α Therapeutics Differentially Affect Leishmania Infection of Human Macrophages
2018
Tumor necrosis factor α (TNFα) drives the pathophysiology of human autoimmune diseases and consequently, neutralizing antibodies (Abs) or Ab-derived molecules directed against TNFα are essential therapeutics. As treatment with several TNFα blockers has been reported to entail a higher risk of infectious diseases such as leishmaniasis, we established an in vitro model based on Leishmania-infected human macrophages, co-cultured with autologous T-cells, for the analysis and comparison of anti-TNFα therapeutics. We demonstrate that neutralization of soluble TNFα (sTNFα) by the anti-TNFα Abs Humira®, Remicade®, and its biosimilar Remsima® negatively affects infection as treatment with these agen…
TNFSF14 (LIGHT) Exhibits Inflammatory Activities in Lung Fibroblasts Complementary to IL-13 and TGF-β
2018
The cytokine TNFSF14 [homologous to Lymphotoxin, exhibits Inducible expression and competes with HSV Glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes (LIGHT)] has been shown in mouse models to be important for development of lung tissue remodeling that is characteristic of asthma, idiopathic pulmonary fibrosis (IPF), and systemic sclerosis (SSc). However, its cellular targets are not fully delineated. In the present report, we show that LTβR and HVEM, the receptors for LIGHT, are constitutively expressed in primary human lung fibroblasts (HLFs). We asked whether LIGHT could promote inflammatory and remodeling-relevant activity in HLFs and how this was similar to, or…
The Unfolded Protein Response Plays a Predominant Homeostatic Role in Response to Mitochondrial Stress in Pancreatic Stellate Cells.
2016
Activated pancreatic stellate cells (PaSC) are key participants in the stroma of pancreatic cancer, secreting extracellular matrix proteins and inflammatory mediators. Tumors are poorly vascularized, creating metabolic stress conditions in cancer and stromal cells that necessitate adaptive homeostatic cellular programs. Activation of autophagy and the endoplasmic reticulum unfolded protein response (UPR) have been described in hepatic stellate cells, but the role of these processes in PaSC responses to metabolic stress is unknown. We reported that the PI3K/mTOR pathway, which AMPK can regulate through multiple inputs, modulates PaSC activation and fibrogenic potential. Here, using primary a…
Characterization of EGF-guided MDA-MB-231 cell chemotaxis in vitro using a physiological and highly sensitive assay system
2018
Chemotactic cell migration is a central mechanism during cancer cell invasion and hence metastasis. In order to mimic in vivo conditions, we used a three-dimensional hydrogel matrix made of collagen I and a stable gradient-generating chemotaxis assay system, which is commercially available (μ-Slide Chemotaxis) to characterize epidermal growth factor (EGF)-induced chemotaxis of the human breast cancer cell line MDA-MB-231. Surprisingly, chemotactic effects of EGF on MDA-MB-231 cells could neither be observed in the standard growth medium DMEM/F-12 supplemented with 10% serum nor in starvation medium. In contrast, after adapting the cells to the serum-free growth medium UltraCULTURETM, signif…