Direct and Indirect Effect of TGFβ on Treg Transendothelial Recruitment in HCC Tissue Microenvironment

The balance between anti-tumor and tumor-promoting immune cells, such as CD4+ Th1 and regulatory T cells (Tregs), respectively, is assumed to dictate the progression of hepatocellular carcinoma (HCC). The transforming growth factor beta (TGFβ) markedly shapes the HCC microenvironment, regulating the activation state of multiple leukocyte subsets and driving the differentiation of cancer associated fibroblasts (CAFs). The fibrotic (desmoplastic) reaction in HCC tissue strongly depends on CAFs activity. In this study, we attempted to assess the role of TGFβ on transendothelial migration of Th1-oriented and Treg-oriented CD4+ T cells via a direct or indirect, CAF-mediated mechanisms, respectively. We found that the blockage of TGFβ receptor I-dependent signaling in Tregs resulted in impaired transendothelial migration (TEM) of these cells. Interestingly, the secretome of TGFβ-treated CAFs inhibited the TEM of Tregs but not Th1 cells, in comparison to the secretome of untreated CAFs. In addition, we found a significant inverse correlation between alpha-SMA and FoxP3 (marker of Tregs) mRNA expression in a microarray analysis involving 78 HCCs, thus suggesting that TGFβ-activated stromal cells may counteract the trafficking of Tregs into the tumor. The apparent dual behavior of TGFβ as both pro- and anti-tumorigenic cytokines may add a further level of complexity to the mechanisms that regulate the interactions among cancerous, stromal, and immune cells within HCC, as well as other solid tumors, and contribute to better manipulation of the TGFβ signaling as a therapeutic target in HCC patients.     

Microstructural characterization and in vitro bioactivity of porous glass-ceramic scaffolds for bone regeneration by synchrotron radiation X-ray microtomography

One of the key purposes of bone tissue engineering is the development of new biomaterials that can stimulate the body's own regenerative mechanism for patient's anatomical and functional recovery. Bioactive glasses, due to their versatile properties, are excellent candidates to fabricate porous 3-D architectures for bone replacement. In this work, morphological and structural investigations are carried out on Bioglass^®- and CEL2-derived scaffolds produced by sponge replication (CEL2 is an experimental glass developed at Politecnico di Torino). Synchrotron radiation X-ray microtomography is used to study the samples 3-D architecture, pores size, shape, distribution and interconnectivity, as well as the growth kinetics on scaffolds struts of a newly formed apatitic phase during in vitro treatment in simulated body fluid, in order to describe from a quantitative viewpoint the bioactive potential of the analyzed biomaterials. An accurate comparison between architectural features and bioactive behaviour of Bioglass^®- and CEL2-derived scaffolds is presented and discussed.     

The Anti-Inflammatory Effects of the Methanolic Extract and Fractions from Davilla elliptica St. Hil. (Dilleniaceae) on Bothrops jararaca Envenomation

Inflammation and haemorrhage are the main characteristics of tissue injury in botropic envenomation. Although some studies have shown that anti-venom prevents systemic reactions, it is not efficient in preventing tissue injury at the site of the bite. Therefore, this work was undertaken to investigate the anti-inflammatory effects of the methanolic extract and fractions from D. elliptica and to evaluate the role of matrix metalloproteinases (MMPs) in this process. Effects of the extract and fractions from D. elliptica were evaluated using a carrageenan-induced paw oedema model in rats, and leukocyte rolling was visualized by intravital. The quantification of MMPs activities (MMP-2 and MMP-9) extracted from the dermis of mice treated with extract and fractions alone or incubated with venom was determined by zymographic analyses. Our results show that intraperitoneal (i.p.) injection of fractions significantly reduced paw oedema after the carrageenan challenge. Treatment with the tannins fraction also resulted in considerable inhibition of the rolling of leukocytes and this fraction was able to decrease the activation of MMP-9. These results confirmed the anti-inflammatory activity of the methanolic extract and tannins fraction of D. elliptica and showed that the dermonecrosis properties of B. jararaca venom might be mediated through the inhibition of MMP-9 activity.     

Some recent advances in polyolefin functionalization

Polyolefin‐based materials are increasingly being used in many industrial applications for packaging, automotive and construction materials. The recent developments of research have been aimed at making these materials, often complex, being mixtures, block copolymers, micro‐ and nanocomposites with inorganic and organic fillers, more efficient and environmentally friendly (through recycling processes, and the use of bio‐polyolefins). In this context, functionalized polyolefins, on the one hand, play a fundamental role in improving the morphology and thus the thermal and mechanical properties of heterophase systems, and, on the other hand, provide new materials difficult to obtain by conventional synthesis in connection with the type of inserted functionality. Therefore it appears to be of interest to report and discuss here the recent results concerning the radical grafting in the melt of different functionalities onto polyolefins as well as the capability reached of modulating ad hoc the degree of grafting and the final structure/architecture of functionalized polyolefins. © 2013 Society of Chemical Industry     

Landscape features control river's confluences water quality and tributary fish composition

Rivers networks represent hierarchical dendritic habitats within terrestrial landscapes and differences in connectivity and land use influence dispersal, and consequently biodiversity patterns. We, therefore, measured variation in water chemistry and fish abundance and related these to a number of landscape characteristics (e.g., wetland, urban, wooded, and agricultural) in the River Klarälven and its 30 permanently flowing tributaries. We hypothesized that these environmental attributes would differ between tributary and main stem habitat and that these differences would be driven by landscape attributes including land use. We found considerable intertributary variation in temperature and nutrient levels, and between the tributaries and the main stem. Generally, water temperature was lower in the tributaries, whereas nutrient levels were higher in the tributaries. The lower water temperature has implications for coldwater fishes, and we found two fishes, burbot and lamprey, associated with coldwater tributaries. We also found an inverse relationship between water quality and anthropogenic land use. Protecting tributaries with low anthropogenic impact will likely become increasingly important with ongoing global warming as they can function as thermal refugia for coldwater fishes. Hence, this study underscores the need to evaluate water courses at regional scales to identify spatial refuges and ensure connectivity.     

Catalytic Hydrogenation of CO2 to Formate Using Ruthenium Nanoparticles Immobilized on Supported Ionic Liquid Phases

Ruthenium nanoparticles (NPs) immobilized on imidazolium-based supported ionic liquid phases (Ru@SILP) act as effective heterogeneous catalysts for the hydrogenation of carbon dioxide (CO₂) to formate in a mixture of water and triethylamine (NEt₃). The structure of the imidazolium-based molecular modifiers is varied systematically regarding side chain functionality (neutral, basic, and acidic) and anion to assess the influence of the IL-type environment on the NPs synthesis and catalytic properties. The resulting Ru@SILP materials contain well-dispersed Ru NPs with diameters in the range 0.8–2.9 nm that are found 2 to 10 times more active for CO₂ hydrogenation than a reference Ru@SiO₂ catalyst under identical conditions. Introduction of sulfonic acid groups in the IL modifiers results in a greatly increased turnover number (TON) and turnover frequency (TOF) at reduced metal loadings. As a result, excellent productivity with TONs up to 16 100 at an initial TOF of 1430 h⁻¹ can be achieved with the Ru@SILP(SO₃H-OAc) catalyst. H/D exchange and other control experiments suggest an accelerated desorption of the formate species from the Ru NPs promoted by the presence of ammonium sulfonate species on Ru@SILP(SO₃H-X) materials, resulting in enhanced catalyst activity and productivity.     

Digital Detection of Single Virus Particles by Multi-Spot,Label-Free Imaging Biosensor on Anti-Reflective Glass

Rapid detection of whole virus particles in biological or environmental samples represents an unmet need for the containment of infectious diseases. Here, an optical device enabling the enumeration of single virion particles binding on antibody or aptamers immobilized on a surface with anti-reflective coating is described. In this regime, nanoparticles adhering to the sensor surface provide localized contributions to the reflected field that become detectable because of their mixing with the interfering waves in the reflection direction. Thus, these settings are exploited to realize a scan-free, label-free, micro-array-type digital assay on a disposable cartridge, in which the virion counting takes place in wide field-of-view imaging. With this approach we could quantify, by enumeration, different variants of SARS-CoV-2 virions interacting with antibodies and aptamers immobilized on different spots. For all tested variants, the aptamers showed larger affinity but lower specificity relative to the antibodies. It is found that the combination of different probes on the same surface enables increasing specificity of detection and dynamic range.     

Cachexia,a Systemic Disease beyond Muscle Atrophy

Cachexia is a complication of dismal prognosis, which often represents the last step of several chronic diseases. For this reason, the comprehension of the molecular drivers of such a condition is crucial for the development of management approaches. Importantly, cachexia is a syndrome affecting various organs, which often results in systemic complications. To date, the majority of the research on cachexia has been focused on skeletal muscle, muscle atrophy being a pivotal cause of weight loss and the major feature associated with the steep reduction in quality of life. Nevertheless, defining the impact of cachexia on other organs is essential to properly comprehend the complexity of such a condition and potentially develop novel therapeutic approaches.     

A State of the Art of Antioxidant Properties of Curcuminoids in Neurodegenerative Diseases

Neurodegenerative diseases represent a set of pathologies characterized by an irreversible and progressive, and a loss of neuronal cells in specific areas of the brain. Oxidative phosphorylation is a source of energy production by which many cells, such as the neuronal cells, meet their energy needs. Dysregulations of oxidative phosphorylation induce oxidative stress, which plays a key role in the onset of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). To date, for most neurodegenerative diseases, there are no resolute treatments, but only interventions capable of alleviating the symptoms or slowing the course of the disease. Therefore, effective neuroprotection strategies are needed. In recent years, natural products, such as curcuminoids, have been intensively explored and studied for their therapeutic potentials in several neurodegenerative diseases. Curcuminoids are, nutraceutical compouns, that owen several therapeutic properties such as anti-oxidant, anti-inflammatory and neuroprotective effects. In this context, the aim of this review was to provide an overview of preclinical and clinical evidence aimed to illustrate the antioxidant effects of curcuminoids in neurodegenerative diseases. Promising results from preclinical studies encourage the use of curcuminoids for neurodegeneration prevention and treatment.