Anti-Osteoporotic Drug Release from Ordered Mesoporous Bioceramics: Experiments and Modeling

The release of a potent bone-resorption inhibitor such as zoledronate from a versatile drug delivery system such as SBA 15 has been modeled. The initial and boundary conditions have been defined, together with the system parameters, including the determination of equilibrium and transport parameters. Additionally, the experimental model of the same system has been observed to validate the prediction here developed. This approach represents a powerful tool for the designing of mesoporous implantable drug delivery systems because their release kinetics can be predicted in advance, and this leads to a considerable time and resources saving.     

Oxidative stress and neurodegeneration: the involvement of iron

Many evidences indicate that oxidative stress plays a significant role in a variety of human disease states, including neurodegenerative diseases. Iron is an essential metal for almost all living organisms due to its involvement in a large number of iron-containing proteins and enzymes, though it could be also toxic. Actually, free iron excess generates oxidative stress, particularly in brain, where anti-oxidative defences are relatively low. Its accumulation in specific regions is associated with pathogenesis in a variety of neurodegenerative diseases (i.e., Parkinson’s disease, Alzheimer’s disease, Huntington’s chorea, Amyotrophic Lateral Sclerosis and Neurodegeneration with Brain Iron Accumulation). Anyway, the extent of toxicity is dictated, in part, by the localization of the iron complex within the cell (cytosolic, lysosomal and mitochondrial), its biochemical form, i.e., ferritin or hemosiderin, as well as the ability of the cell to prevent the generation and propagation of free radical by the wide range of antioxidants and cytoprotective enzymes in the cell. Particularly, ferrous iron can act as a catalyst in the Fenton reaction that potentiates oxygen toxicity by generating a wide range of free radical species, including hydroxyl radicals (·OH). The observation that patients with neurodegenerative diseases show a dramatic increase in their brain iron content, correlated with the production of reactive oxigen species in these areas of the brain, conceivably suggests that disturbances in brain iron homeostasis may contribute to the pathogenesis of these disorders. The aim of this review is to describe the chemical features of iron in human beings and iron induced toxicity in neurodegenerative diseases. Furthermore, the attention is focused on metal chelating drugs therapeutic strategies.     

MPEG-PCL Copolymeric Micelles for Encapsulation of Azithromycin

Macrolide antibiotics are lipophilic drugs with some limitations including low solubility, limited cellular permeation, patients discomfort, etc. With amphiphilic methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (MPEG-PCL) copolymer and azithromycin (AZT) as drug carrier and model drug, AZT-loaded micelles were prepared via thin-membrane hydration method in order to overcome these limitations. Encapsulation efficiency of AZT-loaded micelles was 94.40% with good storage stability for 28 days, and AZT’s water solubility was enhanced to 944 μg/mL. Fourier transform infrared spectrum and x-ray diffraction analysis indicated that AZT was enveloped into the micelles in amorphous form due to its interaction with the copolymer. AZT’s in vitro release from the AZT-loaded micelles demonstrated a slow and continuous behavior when compared with raw AZT. The release dynamics was accorded with Weibull equation, meaning that release amount of AZT lowered with time and was proportional to remaining amount of drug in the AZT-loaded micelles. Korsmeyer-Peppas fitting result suggested that drug release process was a classical Fickian diffusion-controlled manner. With Staphylococcus aureus as bacterial strain, antibacterial activity of the AZT-loaded micelles displayed was comparable with raw AZT. In conclusion, MPEG-PCL should be a promising carrier for macrolide antibiotic delivery in treatment of bacterial infections.     

Selenite and ebselen supplementation attenuates <Emphasis Type="SmallCaps">d</Emphasis>-galactose-induced oxidative stress and increases expression of SELR and SEP15 in rat lens

Selenite and ebselen supplementation has been shown to possess anti-cataract potential in some experimental animal models of cataract, however, the underlying mechanisms remain unclear. The present study was designed to evaluate the anti-cataract effects and the underlying mechanisms of selenite and ebselen supplementation on galactose induced cataract in rats, a common animal model of sugar cataract. Transmission electron microscopy images of lens fiber cells (LFC) and lens epithelial cells (LEC) were observed in d-galactose-induced experimental cataractous rats treated with or without selenite and ebselen, also redox homeostasis and expression of proteins such as selenoprotein R (SELR), 15kD selenoprotein (SEP15), superoxide dismutase 1 (SOD1), catalase (CAT), β-crystallin protein, aldose reductase (AR) and glucose-regulated protein 78 (GRP78) were estimated in the lenses. The results showed that d-galactose injection injured rat lens and resulted in cataract formation; however, selenite and ebselen supplementation markedly alleviated ultrastructural injury of LFC and LEC. Moreover, selenite and ebselen supplementation could mitigate the oxidative damage in rat lens and increase the protein expressions of SELR, SEP15, SOD1, CAT and β-crystallin, as well as decrease the protein expressions of AR and GRP78. Taken together, these findings for the first time reveal the anti-cataract potential of selenite and ebselen in galactosemic cataract, and provide important new insights into the anti-cataract mechanisms of selenite and ebselen in sugar cataract.     

Sedimentary Factors are Key Predictors of Carbon Storage in SE Australian Saltmarshes

Although coastal vegetated ecosystems are widely recognised as important sites of long-term carbon (C) storage, substantial spatial variability exists in quantifications of these ‘blue C’ stocks. To better understand the factors behind this variability we investigate the relative importance of geomorphic and vegetation attributes to variability in the belowground C stocks of saltmarshes in New South Wales (NSW), southeast Australia. Based on the analysis of over 140 sediment cores, we report mean C stocks in the surface metre of sediments (mean ± SE = 164.45 ± 8.74 Mg C ha^?1) comparable to global datasets. Depth-integrated stocks (0–100 cm) were more than two times higher in fluvial (226.09 ± 12.37 Mg C ha^?1) relative to marine (104.54 ± 7.11) geomorphic sites, but did not vary overall between rush and non-rush vegetation structures. More specifically, sediment grain size was a key predictor of C density, which we attribute to the enhanced C preservation capacity of fine sediments and/or the input of stable allochthonous C to predominantly fine-grained, fluvial sites. Although C density decreased significantly with sediment depth in both geomorphic settings, the importance of deep C varied substantially between study sites. Despite modest spatial coverage, NSW saltmarshes currently hold approximately 1.2 million tonnes of C in the surface metre of sediment, although more C may have been returned to the atmosphere through habitat loss over the past approximately 200 years. Our findings highlight the suitability of using sedimentary classification to predict blue C hotspots for targeted conservation and management activities to reverse this trend.     

Landscape genetics of a tropical rescue pollinator

Pollination services are increasingly threatened by the loss and modification of natural habitats, posing a risk to the maintenance of both native plant biodiversity and agricultural production. In order to safeguard pollination services, it is essential to examine the impacts of habitat degradation on the population dynamics of key pollinators and identify potential “rescue pollinators” capable of persisting in these human-altered landscapes. Using a landscape genetic approach, we assessed the impact of landscape structure on genetic differentiation in the widely-distributed tropical stingless bee Trigona spinipes (Apidae: Meliponini) across agricultural landscape mosaics composed of coffee plantations and Atlantic forest fragments in southeastern Brazil. We genotyped 115 bees at 16 specific and highly polymorphic microsatellite loci, developed using next-generation sequencing. Our results reveal that T. spinipes is capable of dispersing across remarkably long distances, as we did not find genetic differentiation across a 200 km range, nor fine-scale spatial genetic structure. Furthermore, gene flow was not affected by forest cover, land cover, or elevation, indicating that reproductive individuals are able to disperse well through agricultural landscapes and across altitudinal gradients. We also found evidence of a recent population expansion, suggesting that this opportunistic stingless bee is capable of colonizing degraded habitats. Our results thus suggest that T. spinipes can persist in heavily-altered landscapes and can be regarded as a rescue pollinator, potentially compensating for the decline of other native pollinators in degraded tropical landscapes.     

Engineering bacteria toward tumor targeting for cancer treatment: current state and perspectives

One of the primary limitations of cancer therapy is lack of selectivity of therapeutic agents to tumor cells. Current efforts are focused on discovering and developing anticancer agents that selectively target only tumor cells and spare normal cells to improve the therapeutic index. The use of preferentially replicating bacteria as an oncolytic agent is one of the innovative approaches for the treatment of cancer. This is based on the observation that some obligate or facultative anaerobic bacteria are capable of multiplying selectively in tumors and inhibiting their growth. Meanwhile, bacteria have been demonstrated to colonize and destroy tumor, and have emerged as biological gene vectors to tumor microenvironment. To improve the efficacy and safety of the bacterial therapy, a further understanding of bacteria between with immune system is required. Furthermore, we want to evaluate how bacterial infection facilitates the “bystander effect” of chemotherapeutic agent and assess if it can be used for additional antitumor effect when combined with chemotherapy. This study may not only evaluate therapeutic efficacy of bacteria for the treatment of cancer but also elucidate the mechanisms underlying antitumor activities mediated by bacteria, which involve host immune responses and the cellular molecular responses.     

Immune suppression in the tumor microenvironment: a role for dendritic cell-mediated tolerization of T cells

Immune suppression remains a consistent obstacle to successful anti-tumor immune responses. As tumors develop, they create a microenvironment that not only supports tumor growth and metastasis but also reduces potential adaptive immunity to tumor antigens. Among the many components of this tumor microenvironment is a population of dendritic cells which exert profound immune suppressive effects on T cells. In this review, we discuss our recent findings related to these tumor-associated dendritic cells and how targeting them may serve to generate more durable anti-tumor immune responses.     

Comparing movement of four butterfly species in experimental grassland strips

In contrast to many studies on the habitat quality of road verges for butterflies in relation to management regimes, little is known about whether road verges also function as corridors linking fragmented grassland habitats. We experimentally compared movements of four model species, two small blues and two medium browns, with one habitat specialist and one habitat generalist in each size and phylogenetic category. A total of 425 individual butterflies were caught and translocated to an experimental arena with three 2 × 30 m grassland strips that approximated road verges; one with adult feeding resources, one sheltered from the wind, and one without food and shelter. Movements in grassland strips were compared to movements in continuous grassland habitat. Results indicated that (1) individuals did not use the low-quality strip, (2) only specialists used strips but not in the same way according to their size and phylogenic category, and (3) strip use could not be predicted from habitat selection. This finding supports the idea that corridors of intermediate quality are the most efficient to promote dispersal rates in fragmented landscapes. Road verges cover 250,000 ha in Sweden, which is nearly the total amount of seminatural grasslands. Our results suggest that, to benefit butterfly dispersal among grassland patches, road verges should be managed to create a more favourable microclimate (e.g. sheltered from wind, high temperatures).     

Recent advances in barley transformation

Barley, an important member of the cereals, has been successfully transformed through various methods such as particle bombardment, Agrobacterium tumefaciens, DNA uptake, and electroporation. Initially, the transformation in barley concentrated on developing protocols using marker genes such as gus, bar, and hpt. Immature embryos and callus derived from immature embryos were targeted for transformation. Subsequently, genes of agronomic and malting importance have been deployed in barley. Particle bombardment appears to be the preferred choice for barley transformation in the majority of the reports, although Agrobacterium-mediated transformation is being used more often. The current review focuses on the challenges encountered in barley transformation such as somaclonal variation, development of transformation systems for commercial cultivars, gene expression, stability and inheritance, and gene flow. Newer markers such as the green fluorescent protein (gfp), firefly luciferase, and phosphomannose isomerase were found to be useful in the selection of transgenic plants. Tissue-specific promoters such as those for B1-hordein and D-hordein genes, and spike-specific promoters, are increasingly used to drive gene expression. The review also describes recent research on gene-tagging through transformation, insertion of disease resistance, and abiotic stress resistance genes, transformation with genes for improved malting quality, nutrient content, feed quality, and the production of feed enzymes and pharmaceutical compounds.