Search results for "human cell"
showing 10 items of 20 documents
Self-assembled multivalent (SAMul) ligand systems with enhanced stability in the presence of human serum
2019
Self-assembled cationic micelles are an attractive platform for binding biologically-relevant polyanions such as heparin. This has potential applications in coagulation control, where a synthetic heparin rescue agent could be a useful replacement for protamine, which is in current clinical use. However, micelles can have low stability in human serum and unacceptable toxicity profiles. This paper reports the optimi- sation of self-assembled multivalent (SAMul) arrays of amphiphilic ligands to bind heparin in competitive conditions. Specifically, modification of the hydrophobic unit kinetically stabilises the self-assembled nanostructures, preventing loss of binding ability in the presence of…
Recombinant factor VIII: past, present and future of treatment of hemophilia A.
2018
The development of recombinant factor VIII (rFVIII) was initially driven by the necessity to treat hemophilia A (HA) patients with FVIII concentrates without the risk of transmitting infectious agents. Over the last three decades the safety of rFVIII has been further improved by completely removing animal or human proteins from the manufacturing process, so that patients would not be exposed to known or emerging pathogens. Recent efforts have concentrated on improving the expression of rFVIII, reducing its immunogenicity and enhancing its pharmacokinetic (PK) behavior. These new goals have been possible thanks to the develop-ment of biotechnology and a better knowledge of the function and s…
Comprehensive evaluation of coding region point mutations in microsatellite-unstable colorectal cancer
2018
Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI colorectal cancers (CRCs), however, also contain more point mutations than microsatellite-stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV. Somatic point mutation data from the exome kit-targeted area from 24 exome-sequenced sporadic MSI CRCs and respective normals, and 12 whole-genome-sequenced sporadic MSI CR…
Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance
2017
International audience; Chronic low-grade inflammation during aging (inflammaging) is associated with cognitive decline and neurodegeneration; however, the mechanisms underlying inflammaging are unclear. We studied a population (n = 361) of healthy young and old adults from the MyoAge cohort. Peripheral levels of C-X-C motif chemokine ligand 10 (CXCL10) was found to be higher in older adults, compared with young, and negatively associated with working memory performance. This coincided with an age-related reduction in blood DNA methylation at specific CpGs within the CXCL10 gene promoter. In vitro analysis supported the role of DNA methylation in regulating CXCL10 transcription. A polymorph…
Distinct single-component adjuvants steer human DC-mediated T-cell polarization via Toll-like receptor signaling toward a potent antiviral immune res…
2021
Significance Vaccines profit from the addition of adjuvants to better and more specifically initiate, amplify, and shape immune responses. Although the number of adjuvant candidates has steadily increased, peaking in the current SARS-CoV-2 pandemic, little is known about their inherent mode of action. Using human blood immune cells, we established a multilayer method to systematically assess the adjuvants’ effects on innate and adaptive immune cells. By employing a multiplex analysis with cells from 30 different donors, we determined important patterns of adjuvant function. Moreover, we demonstrate correlates of an antiviral immune response using a Toll-like receptor 7/8 ligand adjuvant and…
Possible clinical usefulness of embryonic stem cells
2012
Abstract Are embryonic stem cells being used for therapeutic purposes? The aim of this short report is to review to what extent are embryonic stem cells currently used for therapeutic purposes. To the best of our knowledge, only four clinical trials have been authorised so far to use human embryonic stem cells for therapeutic purposes; two of these are included in the ClinicalTrials.gov data base, and the other two, the study sponsored by Geron and the last one initiated by Advanced Cell Technology in the United Kingdom, are not. But, in addition, Geron withdrew the clinical trial which had been originally proposed by the company itself. This brief review focuses the debate on the use of em…
A liquid-culture-based screening approach to study compounds affecting inflammatory processes in Caenorhabditis elegans
2021
Abstract Discovery of biomedical drugs makes use of novel biological sources of limited availability and is often in need of fast, small-scale initial screening approaches. Here, we present a screening, based on the reporter Caenorhabditis elegans strain IG692, for identification of anti- and pro-inflammatory properties. The elaborated workflow is based on cultivation in fluid and by this, allows fast and reproducible seeding in 96 well plates. LPS and dexamethasone served as reliable controls, comparable to application in the human cell line THP-1. This in vivo approach offers a first step for selection of e.g. natural products or for repurposing of compounds from drug libraries and by thi…
Control of MicroRNA Expression as a New Way for Resveratrol To Deliver Its Beneficial Effects
2012
Grapes produce large amounts of polyphenols. Many of them accumulate in the skin, pulp, and seeds and are consequently found in wine. The health benefits of a moderate consumption of wine have been attributed at least in part to grape's polyphenols. Among them, resveratrol (3,5,4'-trihydroxystilbene) is a phytoalexin that stimulates plant cell defenses against infections and also plays protective roles in humans, where it delays cardiovascular alterations and exerts anticancer and anti-inflammatory effects. Despite numerous studies, the molecular mechanisms of resveratrol action are only partially understood. Given its pleiotropic effects, it was previously suggested that resveratrol protec…
Lead optimization through VLAK protocol: New annelated pyrrolo-pyrimidine derivatives as antitumor agents
2012
Abstract The chemometric protocol VLAK was applied to predict improvement of the biological activity of pyrrolo-pyrimidine derivatives as anticancer agents, by using the NCI ACAM Database as depository of antitumor drugs with a known mechanism of action. Among the selected compounds two of these showed a good increase in the antitumor activity. These new pyrrolo-pyrimidine compounds were demonstrated effective against the full panels of NCI DTP tumour human cell lines. The derivative 8-[3-(piperidino)propyl]-4,10-dimethyl-9-phenyl-6-(methylsulfanyl)-3,4-dihydropyrimido[1,2-c]pyrrolo[3,2-e]pyrimidin-2(8H)-one reveled efficacious against the leukemia subpanel, in particular the RPMI cell line…
Concentration-Dependent Protection by Ethanol Extract ofPropolis against γ
2011
[EN] Radioprotection with natural products may be relevant to the mitigation of ionizing radiation-induced damage in mammalian systems; in this sense, propolis extracts have shown effects such as antioxidant, antitumoral, anti-inflammatory, and immunostimulant. We report for the first time a cytogenetic study to evaluate the radioprotective effect, in vitro, of propolis against radiation-induced chromosomal damage. Lymphocytes were cultured with increasing concentrations of ethanol extract of propolis (EEP), including 20, 40, 120, 250, 500, 750, 1000, and 2000 ¿g mL-1 and then exposed to 2 Gy ¿-rays. A significant and concentration-dependent decrease is observed in the frequency of chromoso…