Fe-bLf nanoformulation targets survivin to kill colon cancer stem cells and maintains absorption of iron, calcium and zinc

To validate the anticancer efficacy of alginate-enclosed, chitosan-conjugated, calcium phosphate, iron-saturated bovine lactoferrin (Fe-bLf) nanocarriers/nanocapsules (NCs) with improved sustained release and ability to induce apoptosis by downregulating survivin, as well as cancer stem cells.

Media targets: When a spark in social media develops into a mainstream media storm

This chapter investigates how public relations professionals can best manage social media crises of high interest to mainstream news media. It explores this question through a a case study of mass market retailer Target's 2012 media crisis over its fashions for girls aged 7-14. The case offers insights on the importance of monitoring social media and being prepared to step in and speak up in order to steer the public conversation that now takes place across multiple platforms

Metabotropic glutamate receptors as targets for novel antipsychotic treatments

In recent years metabotropic glutamate receptors have emerged as key targets for the design of new antipsychotic medications for schizophrenia, in particular mGluR5 and mGluR2/3. These receptors exhibit diverse interactions with other neurotransmitter receptors and critical elements of intracellular signalling cascades known to be important to the pharmacotherapy of schizophrenia. In addition, mGluR5 and mGluR2/3 are intimately involved in behavioural domains related to the symptoms of this disorder. Both animal and clinical studies using novel drugs targeting these receptors have provided encouraging results. The number of patents registered for drugs targeting metabotropic glutamate receptors has grown dramatically, and positive allosteric modulators for both receptors show particular promise.

EpCAM Aptamer-siRNA chimera targets and regress epithelial cancer

Epithelial cell adhesion molecule (EpCAM), a cancer stem cell (CSC) marker is over expressed in epithelial cancers and in retinoblastoma (RB). We fabricated an EpCAM targeting aptamer-siRNA chimera and investigated its anti-tumor property and EpCAM intracellular domain (EpICD) mediated signaling in epithelial cancer. The anti-tumor efficacy of EpCAM aptamer-siEpCAM chimera (EpApt-siEp) was evaluated by qPCR, northern and Western blotting in WERI-Rb1- RB cell line, primary RB tumor cells and in MCF7- breast cancer cell line. Anti-tumor activity of EpApt-siEp was studied in vivo using epithelial cancer (MCF7) mice xenograft model. The mechanism and pathways involved in the anti-tumor activity was further studied using protein arrays and qPCR. EpApt-siEp chimera was processed in vitro by dicer enzyme. Treatment of the WERI-Rb1 and MCF7 cells with EpApt-siEp revealed statistically significant down regulation of EpCAM expression (P<0.005) and concomitant reduction in cellular proliferation. In primary RB cells cultured from RB tumors, EpApt-siEp silenced EpCAM, significantly inhibited (P<0.01) cell proliferation and induced cytotoxicity. Knockdown of EpICD expressed in RB primary tumors led to repression of pluripotency markers, SOX2, OCT4, NANOG, and CD133. In vivo studies showed complete tumor growth regression without any toxicity in animals (P<0.001) and tumor tissues showed significant downregulation (P<0.05) of EpCAM, MRP1, ABCG2, stathmin, survivin and upregulation of ATM (P<0.05) leading to apoptosis by intrinsic pathway with minor alteration in cytokines. Our results revealed that EpApt-siEp potentially eradicated EpCAM positive cancer cells through CSC marker suppression and apoptosis, while sparing normal EpCAM negative adjacent cells.

The deleterious effects of oxidative and nitrosative stress on palmitoylation, membrane lipid rafts and lipid-based cellular signalling : new drug targets in neuroimmune disorders

Oxidative and nitrosative stress (O&NS) is causatively implicated in the pathogenesis of Alzheimer’s and Parkinson’s disease, multiple sclerosis, chronic fatigue syndrome, schizophrenia and depression. Many of the consequences stemming from O&NS, including damage to proteins, lipids and DNA, are well known, whereas the effects of O&NS on lipoprotein-based cellular signalling involving palmitoylation and plasma membrane lipid rafts are less well documented. The aim of this narrative review is to discuss the mechanisms involved in lipid-based signalling, including palmitoylation, membrane/lipid raft (MLR) and n-3 polyunsaturated fatty acid (PUFA) functions, the effects of O&NS processes on these processes and their role in the abovementioned diseases. S-palmitoylation is a post-translational modification, which regulates protein trafficking and association with the plasma membrane, protein subcellular location and functions. Palmitoylation and MRLs play a key role in neuronal functions, including glutamatergic neurotransmission, and immune-inflammatory responses. Palmitoylation, MLRs and n-3 PUFAs are vulnerable to the corruptive effects of O&NS. Chronic O&NS inhibits palmitoylation and causes profound changes in lipid membrane composition, e.g. n-3 PUFA depletion, increased membrane permeability and reduced fluidity, which together lead to disorders in intracellular signal transduction, receptor dysfunction and increased neurotoxicity. Disruption of lipid-based signalling is a source of the neuroimmune disorders involved in the pathophysiology of the abovementioned diseases. n-3 PUFA supplementation is a rational therapeutic approach targeting disruptions in lipid-based signalling.

Molecular targets in arthritis and recent trends in nanotherapy

Due to its severity and increasing epidemiology, arthritis needs no description. There are various forms of arthritis most of which are disabling, very painful, and common. In spite of breakthroughs in the field of drug discovery, there is no cure for arthritis that can eliminate the disease permanently and ease the pain. The present review focuses on some of the most successful drugs in arthritis therapy and their side effects. Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities. Mechanisms for different forms of arthritis have been discussed along with the molecules that act as potential biomarkers for arthritis. Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers. The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis. The review also focuses on the recent trends in nanoformulation development used for arthritis therapy. This review is, therefore, important because it describes the relevance and need for more arthritis research, it brings forth a critical discussion of successful drugs in arthritis and analyses the key molecular targets. The review also identifies several knowledge gaps in the published research so far along with the proposal of new ideas and future directions in arthritis therapy.

Bovine lactoferrin targets apoptotic and EGFR mechanisms in breast cancer

 This research investigated the anti-cancer effects of milk protein, lactoferrin. It was found that lactoferrin specifically induced cell death in breast cancer cells and was non-toxic to normal mammary gland cells. Key molecular mechanisms targeted by lactoferrin were elucidated in this study which provides important insight into the activity of this protein as an anti-cancer agent.

Can cancer therapy be achieved by bridging apoptosis and autophagy: A method based on microRNA-dependent gene therapy and phytochemical targets

A failure of a cell to self destruct has long been associated with cancer progression and development. The fact that tumour cells may not instigate cell arrest or activate cell death mechanisms upon cancer drug delivery is a major concern. Autophagy is a mechanism whereby cell material can be engulfed and digested while apoptosis is a self-killing mechanism, both capable of hindering multiplication after cell injury. In particular situations, autophagy and apoptosis seem to co-exist simultaneously or interdependently with the aid of mutual proteins. This review covers roles of microRNAs and chemopreventive agents and makes an attempt at outlining possible partnerships in maximizing cancer cell death with minimal normal cell damage.

Equity and Efficiency in Education: motivations and targets

The recently released "Educational PAC" attempts to place basic education at the center of the social debate. We have subsidized this debate, offering a diagnosis of how different education levels can impact individuals' lives through broad and easily interpreted indicators. Initially, we analyze how much each educational level reaches the poorest population. For example, how are those in the bottom strata of income distribution benefited by childcare centers, private secondary education, public university or adult education. The next step is to quantify the return of educational actions, such as their effects on employability and an individual's wages, and even health as perceived by the individual, be that individual poor, middle class or elite. The next part of the research presents evidence of how the main characters in education, aka mothers, fathers and children, regard education. The site available with the research presents a broad, user-friendly database, which will allow interested parties to answer their own questions relative to why people do not attend school, the time spent in the educational system and returns to education, which can all be cross-sectioned with a wide array of socio-demographic attributes (gender, income, etc.) and school characteristics (is it public, are school meals offered, etc.) to find answers to: why do young adults of a certain age not attend school? Why do they miss classes? How long is the school day? Aside from the whys and hows of teaching, the research calculates the amount of time spent in school, resulting from a combination between absence rates, evasion raters and length of the school day. The study presents ranks of indicators referring to objective and subjective aspects of education, such as the discussion of the advantages and care in establishing performance based incentives that aim at guiding the states in the race for better educational indicators.

Digestive enzymes during development of Ceratitis capitata (Diptera:Tephritidae) and effects of SBTI on its digestive serine proteinase targets

SILVA, Fatima C. B. L. et al. Digestive enzymes during development of Ceratitis capitata (Diptera:Tephritidae) and effects of SBTI on its digestive serine proteinase targets. Insect Biochemistry and Molecular Biology, v. 36, p. 561-569, 2006.ISSN: 0965-1748.DOI: 10.1016/j.ibmb.2006.04.004.

Assessment of liquid disposal originated by uranium enrichment at Aramar Experimental Center São Paulo-Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)