Nanoparticles-cell association predicted by protein corona fingerprints

In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells

Nanoparticles-cell association predicted by protein corona fingerprints

In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells

The impact of migration on the health status of Iranians: An integrative literature review

© 2015 Shishehgar et al. Background: Immigration, both voluntary and forced, is driven by social, political and economic factors. Accordingly, some discussions and debates have emerged in recent years about the impact of migration on the health status of migrants. The aim of this review was to identify the impact of migration on the health status of Iranian immigrants and present a conceptual framework to facilitate the design and delivery of services and supports for this particular immigrant group. Methods: Data for this integrative review were collected from Medline, PsycINFO, Scopus, ProQuest, Academic Search Complete, CINAHL, and Google Scholar search engine. The database search was limited to peer-reviewed literature, published in English, between 1980 and 2013. Results: Twenty six articles were included in the review. Analysis revealed several factors influencing the mental health of immigrants, including language insufficiency; unemployment; sense of discrimination; cultural shock; lack of social support; lack of information about health care services; and intimate partner violence. Conclusion: Findings of this review have contributed to development of a conceptual framework that delineates the impact of migration on Iranian immigrants' health. This conceptualization may also help in addressing the needs of other vulnerable groups during the transition phase of migration

Care-seeking decisions for worsening symptoms in heart failure: a qualitative metasynthesis

Purpose: Over 50% of heart failure (HF) patients delay seeking help for worsening symptoms until these reach acute levels and require emergency hospitalisation. This metasynthesis aimed to identify and explore factors influencing timely care-seeking in patients with HF. Methods: Electronic databases searched were Medline, EMBASE and CINAHL. Studies were included if they were peer reviewed journal articles written in English, and reported perspectives of HF patients following qualitative data collection and analysis. Forty articles underwent analysis following the approach of Thomas and Harden. Leventhal's self-regulatory model (SRM) was used to organise the literature. Results: Much of the literature fit within the SRM, however this model did not account for all factors that influence patients’ care-seeking for worsening symptoms. Factors not accounted for included patients’ appraisals of previous care-seeking experiences, perceived system and provider barriers to accessing care, and the influence of external appraisals. When added to factors already represented in the model, such as misattribution of symptoms, not identifying with HF diagnosis, cognitive status, lack of understanding information provided, adaptation to symptoms, and emotional responses, a more comprehensive account of patients’ decision-making was revealed. Implications: This metasynthesis identified factors, as yet unaccounted for, in a prominent model, and has suggested a more comprehensive framework for addressing care-seeking in HF patients. This information can be used to tailor education, communication, and service initiatives to improve HF patients’ responses to worsening symptoms

Allosteric modulators targeting cannabinoid cb1 and cb2 receptors: Implications for drug discovery

Allosteric modulators of cannabinoid receptors hold great therapeutic potential, as they do not possess intrinsic efficacy, but instead enhance or diminish the receptor's response of orthosteric ligands allowing for the tempering of cannabinoid receptor signaling without the desensitization, tolerance and dependence. Allosteric modulators of cannabinoid receptors have numerous advantages over the orthosteric ligands such as higher receptor type selectivity, probe dependence and biased signaling, so they have a great potential to separate the therapeutic benefits from side effects own of orthosteric ligands. This review aims to give an overview of the CB1 and CB2 receptor allosteric modulators highlighting the structure-activity relationship and pharmacological profile of each classes, and their future promise

Disease management interventions for improving self-management in lower-limb peripheral arterial disease

The objective of this review is to systematically review, synthesise and quantify the effects of non-pharmacological and non-surgical chronic disease management interventions targeting self-management for people with lower-limb PAD

Nature-based molecules combined with rivastigmine: A symbiotic approach for the synthesis of new agents against Alzheimer's disease

Starting from nature as original source, new potential agents with pleiotropic activities have been synthesized and evaluated as neuroprotective agents. In this work, novel nature-based hybrids, combining antioxidant motifs with rivastigmine, have been designed and synthesized. The biological results revealed that the new compounds inhibit both AChE and BuChE. In particular, lipoic acid hybrids LA1, LA2, LA3 resulted to be the most potent inhibitors of BuChE showing IC50 values ranging from 340 to 378 nM. Analogously, all the compounds were able to inhibit the self β-amyloid1-42 aggregation. The gallic acid hybrid GA2 as well as the 2-chromonecarboxylic acid hybrids CA1 and CA2 prevented the self-mediated Aβ aggregation with percentages of inhibition ranging from 53% to 59%. Finally, some of them also show potent neuroprotective effects against glutamate-induced cell death and low toxicity in HT22 cells

Synthesis and AT1 affinity evaluation of benzamidophenyl analogs of known AT1 receptor ligands with similar aromatic skeleton

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