Search results for "Tos"
showing 10 items of 12217 documents
Trichomonicidal and parasite membrane damaging activity of bidesmosic saponins from Manilkara rufula.
2017
The infection caused by Trichomonas vaginalis is the most common but overlooked non-viral sexually transmitted disease worldwide. Treatment relies on one class of drugs, the 5-nitroimidazoles, but resistance is widespread. New drugs are urgently needed. We reported the effect of crude and purified saponin fractions of Manilkara rufula against Trichomonas vaginalis. The compound responsible for antitrichomonal activity was isolated and identified as an uncommon bidesmosic saponin, Mi-saponin C. This saponin eliminated parasite viability without toxicity against the human vaginal epithelial line (HMVII). In addition, the isolated saponin fraction improved the metronidazole effect against a me…
Human platelet-rich plasma improves the nesting and differentiation of human chondrocytes cultured in stabilized porous chitosan scaffolds
2017
[EN] The clinical management of large-size cartilage lesions is difficult due to the limited regenerative ability of the cartilage. Different biomaterials have been used to develop tissue engineering substitutes for cartilage repair, including chitosan alone or in combination with growth factors to improve its chondrogenic properties. The main objective of this investigation was to evaluate the benefits of combining activated platelet-rich plasma with a stabilized porous chitosan scaffold for cartilage regeneration. To achieve this purpose, stabilized porous chitosan scaffolds were prepared using freeze gelation and combined with activated platelet-rich plasma. Human primary articular chond…
Genetic 3’UTR variation is associated with human pigmentation characteristics and sensitivity to sunlight
2017
Sunlight exposure induces signalling pathways leading to the activation of melanin synthesis and tanning response. MicroRNAs (miRNAs) can regulate the expression of genes involved in pigmentation pathways by binding to the complementary sequence in their 3'untranslated regions (3'UTRs). Therefore, 3'UTR SNPs are predicted to modify the ability of miRNAs to target genes, resulting in differential gene expression. In this study, we investigated the role in pigmentation and sun-sensitivity traits, as well as in melanoma susceptibility, of 38 different 3'UTR SNPs from 38 pigmentation-related genes. A total of 869 individuals of Spanish origin (526 melanoma cases and 343 controls) were analysed.…
Human neutrophil elastase induces endothelial cell apoptosis by activating the PERK‐CHOP branch of the unfolded protein response
2017
Human neutrophil elastase impacts on atherosclerotic plaque stability by inducing apoptosis in endothelial cells. Our aim was to investigate the proapoptotic mechanism of elastase on endothelial cells and to evaluate the presence of elastase in human plaque material. Human endothelial cells were treated with purified human neutrophil elastase. Apoptosis was assayed by capsase-3/7 activation, TUNEL, and sub-G1 assay. Activation of unfolded protein response (UPR) effector molecules binding Ig protein, soluble X-binding protein-1, protein kinase RNA-like ER kinase (PERK), and C/EBP-homologous protein (CHOP) was analyzed by RT-PCR, immunocytochemistry, and Western blot. Genetic silencing of CHO…
Determinants for Tight and Selective Binding of a Medicinal Dicarbene Gold(I) Complex to a Telomeric DNA G-Quadruplex: a Joint ESI MS and XRD Investi…
2016
International audience; The dicarbene gold(I) complex [Au(9-methylcaffein-8-ylidene)(2)]BF4 is an exceptional organometallic compound of profound interest as a prospective anticancer agent. This gold(I) complex was previously reported to be highly cytotoxic toward various cancer cell lines invitro and behaves as a selective G-quadruplex stabilizer. Interactions of the gold complex with various telomeric DNA models have been analyzed by a combined ESI MS and X-ray diffraction (XRD) approach. ESI MS measurements confirmed formation of stable adducts between the intact gold(I) complex and Tel 23 DNA sequence. The crystal structure of the adduct formed between [Au(9-methylcaffein-8-ylidene)(2)]…
A Shotgun Proteomics Approach Reveals a New Toxic Role for Alzheimer's Disease Aβ Peptide: Spliceosome Impairment.
2017
Proteomic changes have been described in many neurodegenerative diseases, including Alzheimer's disease (AD). However, the early events in the onset of the pathology are yet to be fully elucidated. A cell model system in which LAN5 neuroblastoma cells were incubated for a short time with a recombinant form of Aβ42 was utilized. Proteins extracted from these cells were subjected to shotgun proteomics analysis by LTQ-Orbitrap-MS followed by label-free quantitation. By bioinformatics tools we found that the most significant of those found to be up-regulated were related to cytoskeletal dynamics (Rho related) and membrane-related processes. The most significant of the down-regulated proteins we…
Insulin resistance and hyperandrogenism drive steatosis and fibrosis risk in young females with PCOS
2017
Background and aims Nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) recognize obesity and insulin resistance (IR) as common pathogenic background. We assessed 1) whether PCOS is a risk factor for steatosis, and 2) the impact, in PCOS patients, of IR and hyperandrogenism on steatosis and fibrosis. Methods We considered 202 consecutive Italian PCOS nondiabetic patients and 101 age-matched controls. PCOS was diagnosed applying the Rotterdam diagnostic criteria. Steatosis was diagnosed if hepatic steatosis index (HSI) >36, while fibrosis by using the FIB-4 score. As surrogate estimate of insulin sensitivity we considered the insulin sensitivity index (ISI). Free an…
Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates
2018
Abstract Neurological disorders are undoubtedly among the most alarming diseases humans might face. In treatment of neurological disorders, the blood‐brain barrier (BBB) is a challenging obstacle preventing drug penetration into the brain. Advances in dendrimer chemistry for central nervous system (CNS) treatments are presented here. A poly(amido)amine (PAMAM) dendrimer bioconjugate with a streptavidin adapter for the attachment of dendrons or any biotinylated drug is constructed. In vitro studies on porcine or murine models and in vivo mouse studies are performed and reveal the permeation of dendronized streptavidin (DSA) into the CNS. The bioconjugate is taken up mainly by the caveolae pa…
Consensus molecular subtypes of colorectal cancer are recapitulated in in vitro and in vivo models
2018
Colorectal cancer (CRC) is a highly heterogeneous disease both from a molecular and clinical perspective. Several distinct molecular entities, such as microsatellite instability (MSI), have been defined that make up biologically distinct subgroups with their own clinical course. Recent data indicated that CRC can be best segregated into four groups called consensus molecular subtypes (CMS1-4), each of which has a unique biology and gene expression pattern. In order to develop improved, subtype-specific therapies and to gain insight into the molecular wiring and origin of these subtypes, reliable models are needed. This study was designed to determine the heterogeneity and identify the prese…
Bioprotection Can Be Tuned with Proper Protein/Saccharide Ratio: The Case of Solid Amorphous Matrices
2018
Saccharides, and in particular trehalose, are well known for their high efficiency in protecting biostructures against adverse environmental conditions. The protein dynamics is known to be highly inhibited in a low-water trehalose host medium, the inhibition being markedly dependent on the amount of residual water. Besides hydration, the protein/sugar ratio is expected to affect the properties of saccharide amorphous matrices. In this work, we report an infrared spectroscopy study in dry amorphous matrices of various sugars (the disaccharides trehalose, maltose, sucrose, and lactose, and the trisaccharide raffinose) containing myoglobin, at different protein/sugar ratios. We analyze the str…