44 research outputs found
The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy
Relevant and selective activity of Pancratium illyricum L. against Candida albicans clinical isolates: a combined effect on yeast growth and virulence
BACKGROUND: Alkaloids present in plants of the Amaryllidaceae family are secondary metabolites of high biological interest, possessing a wide range of pharmacological activities. In the search for new plant-derived compounds with antimicrobial activities, two alkaloid extracts obtained from bulbs and leaves of Pancratium illyricum L., a plant of the Amarillydaceae family, were tested for their effect on bacterial and yeast growth.
METHODS: The broth microdilution susceptibility test was applied to study the effect of plant extracts on the growth of reference bacterial strains and Candida albicans reference and clinical isolates strains. Extracts obtained from the different parts of the plant were tested and compared with the pure components identified in the extracts. Since matrix metalloproteinase enzymes play a role in the dissemination process of Candida albicans, the effect of the bulb extract and pure alkaloids on in vitro collagenase activity was tested. Cell viability test was carried out on human embryo lung fibroblasts (HEL 299).
RESULTS: Whilst both extracts did not show any inhibitory activity against neither Gram positive nor Gram negative bacteria, a strong antifungal activity was detected, in particular for the bulb extract. All clinical isolates were susceptible to the growth inhibitory activity of the bulb extract, with endpoint IC50 values ranging from 1.22 to 78 μg/mL. The pure alkaloids lycorine and vittatine, identified as components of the extract, were also assayed for their capacity of inhibiting the yeast growth, and lycorine turned very active, with endpoint IC50 values ranging from 0.89 to 28.5 μg/mL. A potent inhibition of the in vitro collagenase activity was found in the presence of the bulb extract, and this effect was much higher than that exerted by the pure alkaloids. Viability of cell lines tested was not affected by the extract.
CONCLUSIONS: Taken together, results suggest that the extract of Pancratium illyricum may act as antifungal agent both directly on the yeast growth and by altering the tissue invasion process
Depletion of tumor-associated macrophages switches the epigenetic profile of pancreatic cancer infiltrating T cells and restores their anti-tumor phenotype
Epigenetic signature in T helper 17 and regulatory T cells in multiple sclerosis patients during pregnancy
E2 regulates epigenetic signature on neuroglobin enhancer-promoter in neuronal cells
Estrogens are neuroprotective factors in several neurological diseases. Neuroglobin (NGB) is one of the estrogen target genes involved in neuroprotection, but little is known about its transcriptional regulation. Estrogen genomic pathway in gene expression regulation is mediated by estrogen receptors (ERα and ERβ) that bind to specific regulatory genomic regions. We focused our attention on 17β-estradiol (E2)-induced NGB expression in human differentiated neuronal cell lines (SK-N-BE and NT-2). Previously, using bioinformatics analysis we identified a putative enhancer in the first intron of NGB locus. Therefore, we observed that E2 increased the enrichment of the H3K4me3 epigenetic marks at the promoter and of the H3K4me1 and H3K27Ac at the intron enhancer. In these NGB regulatory regions, we found estrogen receptor alpha (ERα) binding suggesting that ERα may mediate chromatin remodeling to induce NGB expression upon E2 treatment. Altogether our data show that NGB expression is regulated by ERα binding on genomic regulatory regions supporting hormone therapy applications for the neuroprotection against neurodegenerative diseases
A Novel Functional Domain of Tab2 Involved in the Interaction with Estrogen Receptor Alpha in Breast Cancer Cells
Tab2, originally described as a component of the inflammatory pathway, has been implicated in phenomena of gene de-repression in several contexts, due to its ability to interact with the NCoR corepressor. Tab2 interacts also with steroid receptors and dismisses NCoR from antagonist-bound Estrogen and Androgen Receptors on gene regulatory regions, thus modifying their transcriptional activity and leading to pharmacological resistance in breast and prostate cancer cells. We demonstrated previously that either Tab2 knock-down, or a peptide mimicking the Estrogen Receptor alpha domain interacting with Tab2, restore the antiproliferative response to Tamoxifen in Tamoxifen-resistant breast cancer cells. In this work, we map the domain of Tab2 responsible of Estrogen Receptor alpha interaction. First, using both co-immunoprecipitation and pull-down with recombinant proteins, we found that the central part of Tab2 is primarily responsible for this interaction, and that this region also interacts with Androgen Receptor. Then, we narrowed down the essential interaction region by means of competition assays using recombinant protein pull-down. The interaction motif was finally identified as a small region adjacent to, but not overlapping, the Tab2 MEKK1 phosphorylation sites. A synthetic peptide mimicking this motif efficiently displaced Tab2 from interacting with recombinant Estrogen Receptor alpha in vitro, prompting us to test its efficacy using derivatives of the MCF7 breast carcinoma cell lines that are spontaneously resistant to Tamoxifen. Indeed, we observed that this mimic peptide, made cell-permeable by addition of the TAT minimal carrier domain, reduced the growth of Tamoxifen-resistant MCF7 cells in the presence of Tamoxifen. These data indicate a novel functional domain of the Tab2 protein with potential application in drug design
Aiuto medico a morire e diritto: per la costruzione di un dibattito pubblico plurale e consapevole - Documento di sintesi del gruppo di lavoro in materia di aiuto medico al morire.
Mucuna pruriens in Parkinson Disease: A Kinetic-Dynamic Comparison With Levodopa Standard Formulations
Objectives: We compared levodopa (LD) kinetic-dynamic profile of a
dose of LD/aromatic amino acid decarboxylase peripheral inhibitors versus
a nominally equivalent dose of a commercial Mucuna pruriens (Mucuna)
seeds extract in 2 patients with Parkinson disease chronically taking LD
standard combined with self-prescribed Mucuna.
Methods: Patients were challenged with a fasting morning dose of
100 mg LD/25 mg carbidopa (patient 1) or benserazide (patient 2) versus
100 mg LD from Mucuna capsules in 2 different sessions, after a 12-hour
standard LD formulations\u2019 washout. They underwent kinetic-dynamic LD
monitoring based on LD dose intake and simultaneous serial assessments
of plasma drug concentrations and motor test performances. Quantitative
analysis of LD in Mucuna capsules was also performed.
Results: Levodopa bioavailability was markedly lower after Mucuna
administration compared with LD standard formulations: in patient 1, peak
plasma LD concentration (Cmax) decreased from 2.0 to 1.0 mg/L and the
area under the plasma concentration time curve from 137 to 33.6 mg/L
per minute; in patient 2, Cmax was 0.7 mg/L after LD/benserazide and
nearly undetectable afterMucuna. In patient 1, impaired LD bioavailability
from Mucuna resulted in reduced duration and overall extent of drug
response compared with LD/carbidopa. In patient 2, no significant subacute
LD motor response was observed in either condition. Quantitative
analysis of Mucuna formulation confirmed the 100 mg LD content for
the utilized capsules.
Conclusions: Our results show an impaired LD bioavailability from
Mucuna preparation, as expected by the lacking aromatic amino acid decarboxylase
inhibitors coadministration,whichmight explain the suggested lower
dyskinetic potential of Mucuna compared with standard LD formulations