Search results for "CELLULAR"

Galactosylated polyaspartamide copolymers for siRNA targeted delivery to hepatocellular carcinoma cells

2017

The limited efficacy of available treatments for hepatocellular carcinoma (HCC) requires the development of novel therapeutic approaches. We synthesized a novel cationic polymer based on α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) for drug delivery to HCC cells. The copolymer was synthesized by subsequent derivatization of PHEA with diethylene triamine (DETA) and with a polyethylene glycol (PEG) derivative bearing galactose (GAL) molecules, obtaining the cationic derivative PHEA-DETA-PEG-GAL. PHEA-DETA-PEG-GAL has suitable chemical-physical characteristics for a potential systemic use and can effectively deliver a siRNA (siE2F1) targeted against the transcription factor E2F1, a gen…

“Mitotic Slippage” and Extranuclear DNA in Cancer Chemoresistance: A Focus on Telomeres

2020

Mitotic slippage (MS), the incomplete mitosis that results in a doubled genome in interphase, is a typical response of TP53-mutant tumors resistant to genotoxic therapy. These polyploidized cells display premature senescence and sort the damaged DNA into the cytoplasm. In this study, we explored MS in the MDA-MB-231 cell line treated with doxorubicin (DOX). We found selective release into the cytoplasm of telomere fragments enriched in telomerase reverse transcriptase (hTERT), telomere capping protein TRF2, and DNA double-strand breaks marked by γH2AX, in association with ubiquitin-binding protein SQSTM1/p62. This occurs along with the alternative lengthening of telomeres (ALT) and DNA repa…

Fitness Trade-Offs Determine the Role of the Molecular Chaperonin GroEL in Buffering Mutations

2015

Molecular chaperones fold many proteins and their mutated versions in a cell and can sometimes buffer the phenotypic effect of mutations that affect protein folding. Unanswered questions about this buffering include the nature of its mechanism, its influence on the genetic variation of a population, the fitness trade-offs constraining this mechanism, and its role in expediting evolution. Answering these questions is fundamental to understand the contribution of buffering to increase genetic variation and ecological diversification. Here, we performed experimental evolution, genome resequencing, and computational analyses to determine the trade-offs and evolutionary trajectories of Escherich…

l-Glutamate receptor binding in bovine retina

1982

Using a centrifugation technique saturable specific [ 3 H]glutamate binding in bovine retina could be demonstrated. Scatchard analysis revealed only one population of binding sites with a dissociation constant of about 3 μ m and a maximal number of binding sites of about 0·2 pmol/mg retinal protein. Several glutamic acid analogues inhibit specific [ 3 H]glutamate binding in bovine retina with half-maximal inhibitory concentrations similar to those reported in other areas of the CNS. Specific [ 3 H]glutamate binding and sodium dependent synaptosomal uptake of glutamate are largely concentrated in the P2 fraction of bovine retina homogenates consisting of conventionally sized synaptosomes. Th…

Anti-proliferative effect of main dietary phytosterols and β-cryptoxanthin alone or combined in human colon cancer Caco-2 cells through cytosolic Ca+…

2015

β-cryptoxanthin (β-Cx) and phytosterols (Ps) have potential against different cancer types, including colon cancer. However, their combined action has not been reported so far. Human colon cancer Caco-2 cells were treated 24 h with β-Cx and/or main dietary Ps (β-sitosterol, campesterol and stigmasterol), alone or in combination, at concentrations compatible with physiological human serum levels. A decrease in cell viability due to apoptosis (rise in sub-G1 population and exposure of membrane phosphatidylserine) was accompanied with dephosphorylation of BAD, mitochondrial depolarization and caspase 3-dependent PARP cleavage, with intracellular Ca2+ influx and increase of RONS levels as initi…

Influence of scaffold pore size on collagen I development: A new in vitro evaluation perspective

2013

Bone tissue engineering takes part in the complex process of bone healing by combining cells, chemical/physical signals, and scaffolds with the scaffolds providing an artificial extracellular matrix network. The role of the support template for cell activity is crucial to guide the healing process. This in vitro study compared three different poly(D,L-lactic acid) scaffolds obtained by varying the pore size generated by applying different salt leaching processes. The influence of pore dimensions on the extracellular matrix produced by human osteosarcoma-derived osteoblasts (MG63 cell line) seeded on these different materials was analyzed. This study is targeted on the intermediate stage of…

Cholesterol Specificity of Some Heptameric β-Barrel Pore-Forming Bacterial Toxins: Structural and Functional Aspects

2010

Apart from the thiol-specific/cholesterol-dependent cytolysin family of toxins (see Chapter 20) there are a number of other unrelated bacterial toxins that also have an affinity for plasma membrane cholesterol. Emphasis is given here on the Vibrio cholerae cytolysin (VCC) and the cytolysins from related Vibrio species. The inhibition of the cytolytic activity of these toxins by prior incubation with extracellular cholesterol or low density lipoprotein emerges as a unifying feature, as does plasma membrane cholesterol depletion. Incubation of VCC with cholesterol produces a heptameric oligomer, which is not equivalent to the pre-pore since it is unable to penetrate the plasma membrane. In st…

Compendio di Immunobiologia Comparata: Poriferi e Cnidari

2014

Fate of aerobic granular sludge in the long-term: The role of EPSs on the clogging of granular sludge porosity

2016

This work aims to investigate the stability of aerobic granular sludge in the long term, focusing on the clogging of the granular sludge porosity exerted by the extracellular polymeric substances (EPSs). The effects of different cycle lengths (short and long-term cycle) on the granular sludge stability were investigated. Results obtained outlined that during the short duration cycle, the formation and breakage of the aerobic granules were continuously observed. During this period, the excess of EPS production contributed to the clogging of the granules porosity, causing their breakage in the long run. During the long-duration cycle, the extended famine period entailed a greater EPSs consump…

Activation of alpha-1A adrenoceptors mobilizes calcium from the intracellular stores in myocytes from rat portal vein.

1994

International audience; Intracellular free Ca++ concentration ([Ca++]i) was monitored using the fluorescence from the dye fura-2-acetoxymethylester in single myocytes from rat portal vein. In the presence of oxodipine (a L-type Ca++ channel inhibitor), norepinephrine (10 microM) evoked transient increases in [Ca++]i which were related to release of Ca++ from intracellular stores. The alpha-1 adrenoceptors mediating intracellular Ca++ release and inositol phosphate accumulation were identified by using subtype-selective agonists and antagonists. Pretreatment with chloroethylclonidine had little effect on the norepinephrine-induced increase in [Ca++]i and inositol phosphate accumulation. In c…