Search results for " Line"

Cytotoxic benzylbenzofuran derivatives from Dorstenia kameruniana

2018

Abstract Chromatographic separation of the extract of the roots of Dorstenia kameruniana (family Moraceae) led to the isolation of three new benzylbenzofuran derivatives, 2-(p-hydroxybenzyl)benzofuran-6-ol (1), 2-(p-hydroxybenzyl)-7-methoxybenzofuran-6-ol (2) and 2-(p-hydroxy)-3-(3-methylbut-2-en-1-yl)benzyl)benzofuran-6-ol(3) (named dorsmerunin A, B and C, respectively), along with the known furanocoumarin, bergapten (4). The twigs of Dorstenia kameruniana also produced compounds 1–4 as well as the known chalcone licoagrochalcone A (5). The structures were elucidated by NMR spectroscopy and mass spectrometry. The isolated compounds displayed cytotoxicity against the sensitive CCRF-CEM and …

Chemical Composition, In Vitro Antitumor and Pro-Oxidant Activities of Glandora rosmarinifolia (Boraginaceae) Essential Oil

2018

The biological properties of essential oils have been demonstrated in the treatment of several diseases and to enhance the bioavailability of other drugs. In natural habitats the essential oils compounds may play important roles in the protection of the plants as antibacterials, antivirals, antifungals, insecticides and also against herbivores by reducing their appetite for such plants or by repelling undesirable others. We analyzed by gas-chromatography mass spectrometry the chemical composition of the essential oil of aerial parts of Glandora rosmarinifolia (Ten.) D.C. Thomas obtained by hydrodistillation and verified some biological activities on a panel of hepatocellular carcinoma cell …

2020

The periodontal ligament (PDL) is exposed to different kinds of mechanical stresses such as bite force or orthodontic tooth movement. A simple and efficient model to study molecular responses to mechanical stress is the application of compressive force onto primary human periodontal ligament fibroblasts via glass disks. Yet, this model suffers from the need for primary cells from human donors which have a limited proliferative capacity. Here we show that an immortalized cell line, PDL-hTERT, derived from primary human periodontal ligament fibroblasts exhibits characteristic responses to glass disk-mediated compressive force resembling those of primary cells. These responses include inductio…

CENP-A Is Dispensable for Mitotic Centromere Function after Initial Centromere/Kinetochore Assembly

2016

SummaryHuman centromeres are defined by chromatin containing the histone H3 variant CENP-A assembled onto repetitive alphoid DNA sequences. By inducing rapid, complete degradation of endogenous CENP-A, we now demonstrate that once the first steps of centromere assembly have been completed in G1/S, continued CENP-A binding is not required for maintaining kinetochore attachment to centromeres or for centromere function in the next mitosis. Degradation of CENP-A prior to kinetochore assembly is found to block deposition of CENP-C and CENP-N, but not CENP-T, thereby producing defective kinetochores and failure of chromosome segregation. Without the continuing presence of CENP-A, CENP-B binding …

Transcriptome-based repurposing of apigenin as a potential anti-fibrotic agent targeting hepatic stellate cells

2017

AbstractWe have used a computational approach to identify anti-fibrotic therapies by querying a transcriptome. A transcriptome signature of activated hepatic stellate cells (HSCs), the primary collagen-secreting cell in liver, and queried against a transcriptomic database that quantifies changes in gene expression in response to 1,309 FDA-approved drugs and bioactives (CMap). The flavonoid apigenin was among 9 top-ranked compounds predicted to have anti-fibrotic activity; indeed, apigenin dose-dependently reduced collagen I in the human HSC line, TWNT-4. To identify proteins mediating apigenin’s effect, we next overlapped a 122-gene signature unique to HSCs with a list of 160 genes encoding…

Enhanced autophagic-lysosomal activity and increased BAG3-mediated selective macroautophagy as adaptive response of neuronal cells to chronic oxidati…

2019

Oxidative stress and a disturbed cellular protein homeostasis (proteostasis) belong to the most important hallmarks of aging and of neurodegenerative disorders. The proteasomal and autophagic-lysosomal degradation pathways are key measures to maintain proteostasis. Here, we report that hippocampal cells selected for full adaptation and resistance to oxidative stress induced by hydrogen peroxide (oxidative stress-resistant cells, OxSR cells) showed a massive increase in the expression of components of the cellular autophagic-lysosomal network and a significantly higher overall autophagic activity. A comparative expression analysis revealed that distinct key regulators of autophagy are upregu…

1-ethyl-3-(6-methylphenanthridine-8-il) urea modulates TLR3/9 activation and induces selective pro-inflammatory cytokine expression in vitro.

2017

We have previously demonstrated the nucleic acid binding capacity of phenanthridine derivatives (PHTs). Because nucleic acids are potent inducers of innate immune response through Toll-like receptors (TLRs), and because PTHs bear a structural resemblance to commonly used synthetic ligands for TLR7/8, we hypothesized that PHTs could modulate/activate immune response. We found that compound M199 induces secretion of IL-6, IL-8 and TNFα in human PBMCs and inhibits TLR3/9 activation in different cellular systems (PBMCs, HEK293 and THP-1 cell lines).

The IgG1 B-cell receptor provides survival and proliferative signals analogue to the Igα but not the Igβ co-receptor.

2016

The function of the IgM B-cell receptor (BCR) is dependent on intact signaling of the co-receptors Igα and Igβ, both of which contain a cytoplasmic tail bearing an immunoreceptor tyrosine-based activation motif. We have previously demonstrated that the cytoplasmic tail of the IgG1 BCR can partially compensate for the loss of the signaling moiety of Igα. Here, we show that unlike Igα, Igβ signaling is indispensable for the development and function of IgG1-expressing B cells. Deletion of the cytoplasmic signaling tail of Igβ compromised the survival and proliferation not only of IgM(+) B cells but also of IgG1-expressing B cells. In the absence of the signaling tail of Igβ, the transcription …

Large-scale identification of functional microRNA targeting reveals cooperative regulation of the hemostatic system.

2018

Essentials MicroRNAs (miRNAs) regulate the molecular networks controlling biological functions such as hemostasis. We utilized novel methods to analyze miRNA-mediated regulation of the hemostatic system. 52 specific miRNA interactions with 11 key hemostatic associated genes were identified. Functionality and drugability of miRNA-19b-3p against antithrombin were demonstrated in vivo. SUMMARY: Background microRNAs (miRNAs) confer robustness to complex molecular networks regulating biological functions. However, despite the involvement of miRNAs in almost all biological processes, and the importance of the hemostatic system for a multitude of actions in and beyond blood coagulation, the role o…

Differential binding cell-SELEX method to identify cell-specific aptamers using high-throughput sequencing

2018

AbstractAptamers have in recent years emerged as a viable alternative to antibodies. High-throughput sequencing (HTS) has revolutionized aptamer research by increasing the number of reads from a few (using Sanger sequencing) to millions (using an HTS approach). Despite the availability and advantages of HTS compared to Sanger sequencing, there are only 50 aptamer HTS sequencing samples available on public databases. HTS data in aptamer research are primarily used to compare sequence enrichment between subsequent selection cycles. This approach does not take full advantage of HTS because the enrichment of sequences during selection can be due to inefficient negative selection when using live…