Protein materials as sustainable non- and minimally invasive strategies for biomedical applications

Protein-based materials have found applications in a wide range of biomedical fields because of their biocompatibility, biodegradability and great versatility. Materials of different physical forms including particles, hydrogels, films, fibers and microneedles have been fabricated e.g. as carriers for drug delivery, factors to promote wound healing and as structural support for the generation of new tissue. This review aims at providing an overview of the current scientific knowledge on protein-based materials, and selected preclinical and clinical studies will be reviewed in depth as examples of the latest progress within the field of protein-based materials, specifically focusing on non- and minimally invasive strategies mainly for topical application

metabolic approach to the enhancement of antitumor effect of chemotherapy a key role of acetyl l carnitine

Purpose: Acetyl-l-carnitine (ALC) plays a relevant role in energy metabolism and stress response because of its function in the complex metabolic system regulating the acetyl-CoA levels that provide a source of acetyl groups for metabolic and acetylation-regulated processes. Because acetylation may influence p53 activity/stability and, therefore, the response to platinum compounds, this study was designed to investigate the effect of ALC in combination with platinum compounds. Experimental Design: The antiproliferative and antitumor activity studies were done in a panel of human tumor cell lines with functional or defective p53. The antimetastatic drug efficacy was investigated in the s.c. growing H460/M tumor subline, which is able to generate lung metastases. Results: ALC enhanced the sensitivity to cisplatin of tumor cells with functional p53. The sensitization by ALC was reflected in an improved in vivo antitumor efficacy of the combination over cisplatin alone in wild-type p53 lung tumors. ALC did not increase the cisplatin efficacy in the p53-mutant SW620 tumor. ALC exhibited a significant antimetastatic activity, and this effect was better exploited in combination with the histone deacetylase inhibitor, ST3595. The in vivo ALC/cisplatin combination caused the activation of p53, associated with protein acetylation and induction of target genes. Conclusions: ALC was effective in enhancing the antitumor potential of platinum compounds in wild-type p53 tumors. ALC, alone and in combination with a histone deacetylase inhibitor, exhibited an outstanding antimetastatic activity. Both effects, likely mediated by protein acetylation, may have implications for platinum-based therapy and combinations with histone deacetylase inhibitors. Clin Cancer Res; 16(15); 3944–53. ©2010 AACR

Online Islamic organizations and measuring Web effectiveness

Experts estimate that websites maintained by various Islamic extremists have increased to hundreds in recent years. Innovative operational capabilities enabled by Internet technology certainly pose serious challenges to U.S. counter-terrorism efforts. However, greater attention must be given to Islamic organizations that wage information campaigns, perpetuating resentment and discredit against the United States and her allies. While these sites may not openly call for violence, the sharing of common causes and goals with extremist organizations is worrisome. The repudiation of Western systems and global Islamization under the Shariah systems is often a transparent theme. The purpose of this thesis is to evaluate the effectiveness of these websites at attracting and engaging audiences to promote their cause by applying a web performance methodology commonly accepted in the commercial industry.http://archive.org/details/onlineislamicorg109451273Lieutenant, United States NavyApproved for public release; distribution is unlimited

Increased carrier peptide stability through ph adjustment improves insulin and pth(1-34) delivery in vitro and in vivo rather than by enforced carrier peptide-cargo complexation

Oral delivery of therapeutic peptides is hampered by their large molecular size and labile nature, thus limiting their permeation across the intestinal epithelium. Promising approaches to overcome the latter include co-administration with carrier peptides. In this study, the cell-penetrating peptide penetratin was employed to investigate effects of co-administration with insulin and the pharmacologically active part of parathyroid hormone (PTH(1-34)) at pH 5, 6.5, and 7.4 with respect to complexation, enzymatic stability, and transepithelial permeation of the therapeutic peptide in vitro and in vivo. Complex formation between insulin or PTH(1-34) and penetratin was pH-dependent. Micron-sized complexes dominated in the samples prepared at pH-values at which penetratin interacts electrostatically with the therapeutic peptide. The association efficiency was more pronounced between insulin and penetratin than between PTH(1-34) and penetratin. Despite the high degree of complexation, penetratin retained its membrane activity when applied to liposomal structures. The enzymatic stability of penetratin during incubation on polarized Caco-2 cell monolayers was pH-dependent with a prolonged half-live determined at pH 5 when compared to pH 6.5 and 7.4. Also, the penetratin-mediated transepithelial permeation of insulin and PTH(1-34) was increased in vitro and in vivo upon lowering the sample pH from 7.4 or 6.5 to 5. Thus, the formation of penetratin-cargo complexes with several molecular entities is not prerequisite for penetratin-mediated transepithelial permeation a therapeutic peptide. Rather, a sample pH, which improves the penetratin stability, appears to optimize the penetratin-mediated transepithelial permeation of insulin and PTH(1-34)

Probing ensemble polymorphism and single aggregate structural heterogeneity in insulin amyloid self-assembly

Ensembles of protein aggregates are characterized by a nano- and micro-scale heterogeneity of the species. This diversity translates into a variety of effects that protein aggregates may have in biological systems, both in connection to neurodegenerative diseases and immunogenic risk of protein drug products. Moreover, this naturally occurring variety offers unique opportunities in the field of protein-based biomaterials. In the above-mentioned fields, the isolation and structural analysis of the different amyloid types within the same ensemble remain a priority, still representing a significant experimental challenge. Here we address such complexity in the case of insulin for its relevance as biopharmaceutical and its involvement in insulin-derived amyloidosis. By combining Fourier Transform Infrared Microscopy (micro-FTIR) and fluorescence lifetime imaging microscopy (FLIM) we show the occurrence, within the same ensemble of insulin protein aggregates, of a variable β-structure architecture and content not only dependent on the species analyzed (spherulites or fibrils), but also on the position within a single spherulite at submicron scale. We unambiguously reveal that the surface of the spherulites are characterized by β-structures with an enhanced H-bond coupling compared to the core. This information, inaccessible via bulk methods, allows us to relate the aggregate structure at molecular level to the overall morphology of the aggregates. Our findings robustly solve the problem of probing the ensemble and single particle heterogeneity of amyloid samples. Furthermore, we offer a unique, scalable and ready-to-use screening methodology for in-depth characterization of self-assembled structures, being this translatable to material sciences, drug quality control and clinical imaging of amyloid-affected tissues

Economic evaluation of introduction of poplar as biomass crop in Italy

Lignocellulosic biomass production deriving from agro forest species, as well as poplar (Populus spp.), has denoted an increase in last years in UE also thanks to a series of policies aimed at reducing emissions of greenhouse gases and promoting renewable sources. In Italy poplar represents the main agro forest species and it is cultivated according to two different methods: very Short Rotation Coppice (vSRC) and Short Rotation Coppice (SRC). The aim of this paper has been to evaluate the economic feasibility of poplar as energy crop in the southern Italy and specifically to consider its competitiveness with respect to conventional crops. In particular, an economic analysis in a representative case study located in the Sicilian hilly hinterland has been carried out, by comparing the direct costs and incomes of poplar (both vSRC and SRC) and durum wheat. Results showed that only introduction of SRC plantation could increase the farm competitiveness, while vSRC could be economically advantageous only with a substantial increase of biomass market price and/or CAP subsidy. However, the introduction of poplar should grant a better contribution to climate change mitigation with respect to annual crop, improving the greenhouse gases balance and diminishing the environmental impact of agricultural activity

Choice between alternative investments in agriculture: The role of organic farming to avoid the abandonment of rural areas

Sicily has a long tradition in citrus fruit cultivation that, with vineyard and olive tree, represents the main Mediterranean tree crops. Since many Sicilian farmers in recent years have decided to abandon conventional lemon orchards, in this paper we have evaluated the financial sustainability of organic lemon production by comparing it with the conventional one. Financial analysis has been carried out in a case study on the northwestern coast of Sicily, considering a 50-year economic life of an orchard. The results, per hectare of area, showed a clear advantage of organic lemon orchard. This was due to fewer labor requirements and to greater market appreciation for organic products that better ensured a premium price. Moreover, financial indicators of organic lemon orchards and the deployment of environmental-friendly inputs in the production process render these farms competitive and eco-friendly