Innovative Crop Productions for Healthy Food: The Case of Chia (Salvia hispanica L.)

Chia (Salvia hispanica L.) is an ancient crop from Central America which has been recently rediscovered as a source of ω-3 and nutraceuticals in seeds. Besides traditional seed consumption, innovative uses of the plant seeds and leaves have been proposed based on the high protein content and the production of mucilage which lends itself to a range of applications. This chapter reviews research on the plant’s genetics and breeding, quality, and uses. Agronomic studies which have only recently started worldwide are also presented along with results from case studies in Basilicata

The Health Impact Fund: How Might It Work for Novel Anticoagulants in Atrial Fibrillation?

Cardiovascular diseases represent the greatest burden of global disease. Spending on cardiovascular diseases is higher than for other diseases, with the majority being spent on drugs. Therefore, these drugs and these diseases are hugely important to health systems, society, and pharmaceutical companies. The Health Impact Fund represents a new mechanism by which pharmaceutical innovators would be rewarded on the basis of the health impact of their new drugs. This review illustrates the concept of the Health Impact Fund using the example of novel anticoagulants for prevention of stroke and thromboembolism in atrial fibrillation. By considering existing data and the current situation for novel anticoagulants, we suggest that epidemiologic data and modeling techniques can be used to predict future trends in disease and the health impact of new drugs. The Health Impact Fund may offer potential benefits to pharmaceutical companies, patients, and governments and warrants proper investigation

Valorisation of Biowastes for the Production of Green Materials Using Chemical Methods

With crude oil reserves dwindling, the hunt for a sustainable alternative feedstock for fuels and materials for our society continues to expand. The biorefinery concept has enjoyed both a surge in popularity and also vocal opposition to the idea of diverting food-grade land and crops for this purpose. The idea of using the inevitable wastes arising from biomass processing, particularly farming and food production, is, therefore, gaining more attention as the feedstock for the biorefinery. For the three main components of biomass—carbohydrates, lipids, and proteins—there are long-established processes for using some of these by-products. However, the recent advances in chemical technologies are expanding both the feedstocks available for processing and the products that be obtained. Herein, this review presents some of the more recent developments in processing these molecules for green materials, as well as case studies that bring these technologies and materials together into final products for applied usage

Failure rates and functional results for intercalary femur reconstructions after tumour resection

Purpose To compare the results for patients treated with intercalary endoprosthetic replacement (EPR) or intercalary allograft reconstruction for diaphyseal tumours of the femur in terms of: (1) reconstruction failure rates; (2) cause of failure; (3) risk of amputation of the limb; and (4) functional result. Methods Patients with bone sarcomas of the femoral diaphysis, treated with en bloc resection and reconstructed with an intercalary EPR or allograft, were reviewed. A total of 107 patients were included in the study (36 EPR and 71 intercalary allograft reconstruction). No differences were found between the two groups in terms of follow-up, age, gender and the use of adjuvant chemotherapy. Results The probability of failure for intercalary EPR was 36% at 5 years and 22% for allograft at 5 years (p = 0.26). Mechanical failures were the most prevalent in both types of reconstruction. Aseptic loosening and implant fracture are the main cause in the EPR group. For intercalary allograft reconstructions, fracture followed by nonunion was the most common complication. Ten-year risk of amputation after failure for both reconstructions was 3%. There were no differences between the groups in terms of the mean Musculoskeletal Tumor Society score (27.4, range 16–30 vs. 27.6, range 17–30). Conclusions We have demonstrated similar failure rates for both reconstructions. In both techniques, mechanical failure was the most common complication with a low rate of limb amputation and good functional results. Level of evidence Level III, therapeutic study.Peer reviewe

Combined 5-FU and ChoKα Inhibitors as a New Alternative Therapy of Colorectal Cancer: Evidence in Human Tumor-Derived Cell Lines and Mouse Xenografts

<div><p>Background</p><p>Colorectal cancer (CRC) is the third major cause of cancer related deaths in the world. 5-fluorouracil (5-FU) is widely used for the treatment of colorectal cancer but as a single-agent renders low response rates. Choline kinase alpha (ChoKα), an enzyme that plays a role in cell proliferation and transformation, has been reported overexpressed in many different tumors, including colorectal tumors. ChoKα inhibitors have recently entered clinical trials as a novel antitumor strategy.</p><p>Methodology/Principal Findings</p><p>ChoKα specific inhibitors, MN58b and TCD-717, have demonstrated a potent antitumoral activity both <i>in vitro</i> and <i>in vivo</i> against several tumor-derived cell line xenografts including CRC-derived cell lines. The effect of ChoKα inhibitors in combination with 5-FU as a new alternative for the treatment of colon tumors has been investigated both <i>in vitro</i> in CRC-tumour derived cell lines, and <i>in vivo</i> in mouse xenografts models. The effects on thymidilate synthase (TS) and thymidine kinase (TK1) levels, two enzymes known to play an essential role in the mechanism of action of 5-FU, were analyzed by western blotting and quantitative PCR analysis. The combination of 5-FU with ChoKα inhibitors resulted in a synergistic effect <i>in vitro</i> in three different human colon cancer cell lines, and <i>in vivo</i> against human colon xenografts in nude mice. ChoKα inhibitors modulate the expression levels of TS and TK1 through inhibition of E2F production, providing a rational for its mechanism of action.</p><p>Conclusion/Significance</p><p>Our data suggest that both drugs in combination display a synergistic antitumoral effect due to ChoKα inhibitors-driven modulation of the metabolization of 5-FU. The clinical relevance of these findings is strongly supported since TCD-717 has recently entered Phase I clinical trials against solid tumors.</p></div

Induction of apoptosis in SW620, HT29 and DLD-1 cell lines after treatment with ChoKIs.

<p>(A–C) SW620, HT29 and DLD-1 cells were seeded as described under <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064961#s4" target="_blank">Material and Methods</a> and treated with two concentrations of ChoKα inhibitors [TCD-717: 6 µM (left line) or 10 µM (right line); MN58b: 10 µM (left line) or 15 µM (right line)] for 24 h and, where indicated, with 5.5 µM 5-FU or vehicle for an additional 24 h. Protein expression was analyzed by Western blot using polyclonal antibody anti-PARP. Behind each graph, data shows protein levels (PARP/GAPDH) calculated by the mean ± SEM of three independent experiments. (A) SW620. (B) HT29. (C) DLD-1. (D) PARP and ChoKα expression levels in HT29 and SW620 cell lines transfected with a specific ChoKα siRNA determined by Western blot analysis or a control scramble siRNA (scr). Protein expression was analyzed by Western blot using ChoKα monoclonal antibody and polyclonal antibody anti-PARP. Below each Western the ratio PARP/Tubulin is represented. (E) Caspase 3 activity (upper panel) and its cleavage (lower panel) were determined in HT29 cells after treatment with MN58b for 24 h. (F) Caspase 3 enzymatic activity was also measured after transfection of HT29 cells with a ChoKα specific siRNA or a control siRNA (scr) for 48 h. Western blot represents the levels of ChoKα after transfection and its relative reduction normalized to GAPDH levels.</p

TS expression levels in tumor tissues from DLD-1 xenografts after treatment with MN58b plus 5-FU.

<p>Mice were inoculated with DLD-1 cells as indicated under <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064961#s4" target="_blank">Materials and Methods</a> and either left untreated, or treated with MN58b or 5-FU alone or in combination. A) TS expression levels of each experiment group: Control, MN58b, 5-FU and combination group. Tubulin was used as loading control. B) Graph represents mean protein levels as TS/tubulin ratios for each group. Black bars represent total TS/tubulin values; Grey bars represent TS active values. (*) Statistically significant (p<0.05), compared to control group.</p