Exploiting the efficacy of Tyro3 and folate receptors to enhance the delivery of gold nanoparticles into colorectal cancer cells in vitro

Colorectal cancer (CRC) is the fourth most common cancer in the world. Due to its asymptomatic nature, CRC is diagnosed at an advanced stage where the survival rate is <5%. Besides, CRC treatment using chemotherapy, radiotherapy and surgery often causes undesirable side-effects. As such, gold nanoparticles (GNPs) are envisaged in the field for the diagnosis and treatment of CRC. GNPs have unique physical, chemical and electrical properties at the nanoscale which make them suitable for application in biomedicine. However, for GNPs to become clinically effective, their internalisation efficiency in cancer cells must be enhanced. Folate receptor-α (FR) is overexpressed in CRC cells wherein FR helps in the uptake of folic acid within the cells. Tyro3, a novel tyrosine kinase receptor, drives cell proliferation and its overexpression is correlated with poor prognosis in CRC. Their upregulated expression in CRC cells relative to normal cells makes them an ideal target for GNPs using active targeting. Therefore, in this study receptors FR and Tyro3 were simultaneously targeted using specific antibody-coated GNPs in order to enhance the uptake and internalisation of GNPs in CRC cells in vitro. Four different types of coated-GNPs were synthesised GNPs-PEG, GNPs-anti-FR, GNPs-anti-Tyro3 and GNPs-anti-(FR + Tyro3) and incubated (0–50 ng) with three CRC cell lines namely CRL1790, CRL2159 and HCT116. Simultaneous targeting of these receptors by GNPs-anti-(FR + Tyro3) was found to be the most effective in internalisation in CRC cells compared with GNPs targeted singly to FR or Tyro3 (p <0.05). Besides this, results show that Tyro3 mediated similar internalisation efficacy to FR (p <0.05) in CRC cells using ICP-OES

Toxic effects of estradiol E2 on development in the European tree frog (Hyla arborea)

Estrogenic hormones are a major environmental threat to aquatic wildlife. Here we report chronic toxic effects of exposure to the naturally excreted estrogen, 17β-estradiol (E2), on the larval and subadult development of the European tree frog (Hyla arborea), by an experimental setting and long-term monitoring. In addition to the documented impact on sexual development and mating behavior, the general toxicity of human-released estrogens may contribute to global amphibian declines

Minimal conditions on Clifford semigroup congruences

A known result in groups concerning the inheritance of minimal conditions on normal subgroups by subgroups with finite indexes is extended to semilattices of groups [E(S),Se,ϕe,f] with identities in which all ϕe,f are epimorphisms (called q partial groups). Formulation of this result in terms of q congruences is also obtained

Locating functionalized gold nanoparticles using electrical impedance tomography

Objective: An imaging device to locate functionalised nanoparticles, whereby therapeutic agents are transported from the site of administration specifically to diseased tissues, remains a challenge for pharmaceutical research. Here, we show a new method based on electrical impedance tomography (EIT) to provide images of the location of gold nanoparticles (GNPs) and the excitation of GNPs with radio frequencies (RF) to change impedance permitting an estimation of their location in cell models Methods: We have created an imaging system using quantum cluster GNPs as contrast agent, activated with RF fields to heat the functionalized GNPs, which causes a change in impedance in the surrounding region. This change is then identified with EIT. Results: Images of impedance changes of around 80±4% are obtained for a sample of citrate stabilized GNPs in a solution of phosphate-buffered saline. A second quantification was carried out using colorectal cancer cells incubated with culture media, and the internalization of GNPs into the colorectal cancer cells was undertaken to compare them with the EIT images. When the cells were incubated with functionalised GNPs, the change was more apparent, approximately 40±2%. This change was reflected in the EIT image as the cell area was more clearly identifiable from the rest of the area. Significance: EIT can be used as a new method to locate functionalized GNPs in human cells and help in the development of GNP-based drugs in humans to improve their efficacy in the future

One-step simultaneous liquid phase exfoliation-induced chirality in graphene and their chirality-mediated microRNA delivery

Graphene (G) has established itself as an exciting prospect for a broad range of applications owing to its remarkable properties. Recent innovations in chiral nanosystems have led to sensors, drug delivery, catalysis, etc. owing to the stereospecific interactions between various nanosystems and enantiomers. As the molecular structure of G itself is achiral introducing chirality in G by simple attachment of a functional group (a chiral ligand) on the G nanosheet may result in more diverse applications. Herein, we demonstrate direct liquid phase exfoliation and chiral induction in G nanosheets abbreviated as L-graphene and D-graphene in the presence of chiral L-tyrosine and D-tyrosine and by applying high-temperature sonication. The obtained exfoliated nanosheets demonstrated stable chirality confirmed by circular dichroism. Fourier transform infrared (FTIR) spectra, Raman spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and differential scanning calorimetry (DSC) showed functional, structural, morphological, surface, and thermal characteristics of L-graphene and D-graphene. The hemo-compatibility of these chiral graphenes was evaluated for the very first time utilizing human red blood cells. Lastly, for the very first time, an attempt was made to explore enantiomeric binding between chiral L-graphene and D-graphene with microRNA (miR-205) and their possibility towards chirality-mediated gene delivery in prostate cancerous cells

Tourism and the smartphone app: capabilities, emerging practice and scope in the travel domain.

Based on its advanced computing capabilities and ubiquity, the smartphone has rapidly been adopted as a tourism travel tool.With a growing number of users and a wide varietyof applications emerging, the smartphone is fundamentally altering our current use and understanding of the transport network and tourism travel. Based on a review of smartphone apps, this article evaluates the current functionalities used in the domestic tourism travel domain and highlights where the next major developments lie. Then, at a more conceptual level, the article analyses how the smartphone mediates tourism travel and the role it might play in more collaborative and dynamic travel decisions to facilitate sustainable travel. Some emerging research challenges are discussed

Locating Functionalized Gold Nanoparticles Using Electrical Impedance Tomography

Abstract Objective: An imaging device to locate functionalized nanoparticles, whereby therapeutic agents are transported from the site of administration specifically to diseased tissues, remains a challenge for pharmaceutical research. Here, we show a new method based on electrical impedance tomography (EIT) to provide images of the location of gold nanoparticles (GNPs) and the excitation of GNPs with radio frequencies (RF) to change impedance permitting an estimation of their location in cell models Methods: We have created an imaging system using quantum cluster GNPs as a contrast agent, activated with RF fields to heat the functionalized GNPs, which causes a change in impedance in the surrounding region. This change is then identified with EIT. Results: Images of impedance changes of around 804% are obtained for a sample of citrate stabilized GNPs in a solution of phosphate-buffered saline. A second quantification was carried out using colorectal cancer cells incubated with culture media, and the internalization of GNPs into the colorectal cancer cells was undertaken to compare them with the EIT images. When the cells were incubated with functionalized GNPs, the change was more apparent, approximately 402%. This change was reflected in the EIT image as the cell area was more clearly identifiable from the rest of the area. Significance: EIT can be used as a new method to locate functionalized GNPs in human cells and help in the development of GNP-based drugs in humans to improve their efficacy in the future

Significance of the E-W fault system in the geodynamic evolution of the Tunisian Alpine Chain foreland. Example of the Sbiba-Cherichira fault system in central Tunisia

En Tunisie centrale, les bassins mio-plio-quaternaires de Sbiba et de Haffouz sont constitués de dépocentres délimités par des failles de direction proche de E-W, NW-SE, N070 o et N-S. Ces accidents bordiers bien identifiés en sub-surface et dont l’activité a été démontrée aux époques éo-crétacées, ont évolué durant le Néogène et le Quaternaire dans un système de décrochements en relais, alliant des structures compressives (plis N040 o à N080 o E, failles inverses, chevauchements…) et des structures distensives correspondant à des grabens et demi-grabens orientés E-W et N120 o à N150 o E. La région a été affectée du Néogène au Quaternaire inférieur par une succession de régimes tectoniques compressifs (liés aux phases tortonienne et villafranchienne) et extensifs (extension post-tectonique oligo-miocène comme dans l’ensemble du Maghreb, mais aussi existence d’une phase d’extension au Miocène terminal-Pléistocène inférieur synchrone du rifting du Bassin tyrrhénien). Cette alternance compression-extension induit plusieurs inversions de subsidence. L’étude tectonique effectuée aux abords de ces décrochements permet non seulement d’apporter des précisions sur l’évolution spatiale des déformations mais aussi d’établir les relations tectono-sédimentaires caractérisant chaque époque du Mio-Plio-Quatemaire : bassins subsidents sur les décrochements, installation de bassins lacustres sur barrages morphostructuraux, variations d’épaisseur et de faciès liées aux failles synsédimentaires

Systemic and immune manifestations in myelodysplasia: a multicenter retrospective study

OBJECTIVE: The presence of systemic and/or immune manifestations in myelodysplasia has been currently reported. The influence of these manifestations on the natural outcome of myelodysplastic syndrome has to be considered. We present a multicenter retrospective study (2002-2009) of patients with myelodysplastic syndrome disclosing systemic and/or immune manifestations. METHODS: Forty-six patients with myelodysplasia presenting with systemic and/or immune manifestations were compared in terms of survival with 189 patients with myelodysplasia lacking these features. RESULTS: The clinical picture in these cases consisted of fever (13%), arthralgia or arthritis (13%), and cutaneous manifestations (67%). Four cases of systemic vasculitis have been reported in our series, and they have a worse prognosis. Immune anomalies were recorded in 29% of the cases, and the presence of cryoglobulins was also associated with a worse prognosis. CONCLUSION: A difference in survival between patients with myelodysplastic syndrome with systemic manifestations and patients lacking these manifestations has been observed in the presence of systemic vasculitis and/or cryoglobulins