Search results for " Regulation"
showing 10 items of 3187 documents
Identification of biological targets through the correlation between cell line chemosensitivity and protein expression pattern.
2021
Matching biological data sequences is one of the most interesting ways to discover new bioactive compounds. In particular, matching cell chemosensitivity with a protein expression profile can be a useful approach to predict the activity of compounds against definite biological targets. In this review, we discuss this correlation. First, we analyze case studies in which some known drugs, acting on known targets, show a good correlation between their antiproliferative activities and protein expression when a large panel of tumor cells is considered. Then, we highlight how the application of in silico methods based on the correlation between cell line chemosensitivity and gene/protein expressi…
Regulation of kynurenine biosynthesis during influenza virus infection.
2017
Influenza A viruses (IAVs) remain serious threats to public health because of the shortage of effective means of control. Developing more effective virus control modalities requires better understanding of virus–host interactions. It has previously been shown that IAV induces the production of kynurenine, which suppresses T-cell responses, enhances pain hypersensitivity and disturbs behaviour in infected animals. However, the regulation of kynurenine biosynthesis during IAV infection remains elusive. Here we showed that IAV infection induced expression of interferons (IFNs), which upregulated production of indoleamine-2,3-dioxygenase (IDO1), which catalysed the kynurenine biosynthesis. Furt…
Uterine disorders affecting female fertility: what are the molecular functions altered in endometrium?
2020
[EN]: Objective:To determine the molecular functions of genes exhibiting altered expression in the endometrium of women with uterine disorders affecting fertility. Design: Retrospective analysis integrating case and control data from multiple cohorts with endometrium gene expression in women with uterine disorders. Setting: Infertility research department affiliated with a university hospital. Patient(s): Two hundred and forty women, 121 of whom were controls, 119 of whom had endometrial adenocarcinoma (ADC), recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or stage II–IV endometriosis. Intervention(s): None. Main Outcome Measure(s): Genomewide gene expression and alter…
SARS-CoV-2 infection risk assessment in the endometrium: viral infection-related gene expression across the menstrual cycle
2020
Objective To determine the susceptibility of the endometrium to infection by—and thereby potential damage from—SARS-CoV-2. Design Analysis of SARS-Cov-2 infection-related gene expression from endometrial transcriptomic data sets. Setting Infertility research department affiliated with a public hospital. Patient(s) Gene expression data from five studies in 112 patients with normal endometrium collected throughout the menstrual cycle. Intervention(s) None. Main Outcome Measure(s) Gene expression and correlation between viral infectivity genes and age throughout the menstrual cycle. Result(s) Gene expression was high for TMPRSS4, CTSL, CTSB, FURIN, MX1, and BSG; medium for TMPRSS2; and low for…
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…
Does iris(in) bring bad news or good news?
2017
Irisin, a novel myokine produced in response to physical activity, promotes white-to-brown fat transdifferentiation. The name irisin referred to the ancient Greek goddess Iris, the messenger who delivered (bad) news from the gods. In mice, it has been demonstrated that irisin plays a key role in metabolic regulation, energy expenditure and glucose homeostasis. New findings from various studies carried out in both animals and humans suggest that irisin might also have other favorable effects, such as increasing bone cortical mass, preventing hepatic lipid accumulation, and improving cognitive functions, thus mediating many exercise-induced health benefits. However, data on the role and funct…
Aryl Hydrocarbon Receptor in Keratinocytes Is Essential for Murine Skin Barrier Integrity.
2016
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in adaptive cell functions, and it is highly active in the epidermis. AhR ligands can accelerate keratinocyte differentiation, but the precise role of AhR in the skin barrier is unknown. Our study showed that transepidermal water loss, a parameter of skin barrier integrity, is high in AhR-deficient mice. Experiments with conditionally AhR-deficient mouse lines identified keratinocytes as the primary cell population responsible for high transepidermal water loss. Electron microscopy showed weaker intercellular connectivity in the epidermis of keratinocytes in AhR-knockout mice, and gene expression analysi…
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…
Screening of herbal extracts for TLR2- and TLR4-dependent anti-inflammatory effects.
2018
Herbal extracts represent an ample source of natural compounds, with potential to be used in improving human health. There is a growing interest in using natural extracts as possible new treatment strategies for inflammatory diseases. We therefore aimed at identifying herbal extracts that affect inflammatory signaling pathways through toll-like receptors (TLRs), TLR2 and TLR4. Ninety-nine ethanolic extracts were screened in THP-1 monocytes and HeLa-TLR4 transfected reporter cells for their effects on stimulated TLR2 and TLR4 signaling pathways. The 28 identified anti-inflammatory extracts were tested in comparative assays of stimulated HEK-TLR2 and HEK-TLR4 transfected reporter cells to dif…
Allosteric Cross-Talk among Spike’s Receptor-Binding Domain Mutations of the SARS-CoV-2 South African Variant Triggers an Effective Hijacking of Huma…
2021
The rapid and relentless emergence of novel highly transmissible SARS-CoV-2 variants, possibly decreasing vaccine efficacy, currently represents a formidable medical and societal challenge. These variants frequently hold mutations on the Spike protein's receptor-binding domain (RBD), which, binding to the angiotensin-converting enzyme 2 (ACE2) receptor, mediates viral entry into host cells. Here, all-atom molecular dynamics simulations and dynamical network theory of the wild-type and mutant RBD/ACE2 adducts disclose that while the N501Y mutation (UK variant) enhances the Spike's binding affinity toward ACE2, the concomitant N501Y, E484K, and K417N mutations (South African variant) aptly ad…