Effect of a fermented nutraceutical on thioredoxin level and TNF-alpha signalling in cirrhotic patients

The aim of this study is to gain further insights into the possible nutraceutical effect on redox balance via thioredoxin (Trx) modulation and on the intrinsic susceptibility of monocytes to generate an inflammatory response. The study group consisted of thirty-two patients with compensated Child A-C, HCV-related cirrhosis. The patients were supplemented for 6 months with 6g/day of a certified fermented papaya preparation (FPP). Fifteen unsupplemented, age/gender-matched healthy subjects served as controls. The patients filled in a detailed diet-life style questionnaire, and blood samples were collected to test routine biochemistry, Trx, redox status (GSH, GSSG, GSH/GSSG ratio, 4-HNE and alpha-tocopherol). Moreover, isolated monocytes were tested for ex-vivo LPS-stimulated TNF-alpha production and TNF-alpha mRNA. As compared to control, patients with liver cirrhosis showed a significantly higher serum level of Trx. A significant correlation occurred with GSH/GSSG ratio in Child B and C patients. FPP supplementation brought about a significant reduction of Trx with levels comparable to the ones of healthy controls. Ten patients Child C (31.2 percent) showed borderline low levels of alpha-tocopherol while all cirrhotic patients, as a whole, showed a significantly abnormal redox balance. Supplementation with FPP did not modify alpha-tocopherol depletion but significantly improved redox balance parameters. Patients with liver cirrhosis showed a significantly upregulated TNF-alpha production in a time-dependent manner and this effect was more pronounced in more advanced stages of the disease and showed a significant correlation with alpha-tocopherol level. Supplementation with FPP significantly, although partially, downregulated TNF-alpha production from monocytes. Taken altogether, it would appear that the typical oxidative-inflammatory biochemical milieu of these patients is mirrored by a significant TNF-alpha upregulation at a monocyte level while a targeted nutraceutical might be a potentially amenable intervention to be part of validated scheduled treatments.     

Polymer optoelectronic structures for retinal prosthesis

This commentary highlights the effectiveness of optoelectronic properties of polymer semiconductors based on recent results emerging from our laboratory, where these materials are explored as artificial receptors for interfacing with the visual systems. Organic semiconductors based polymer layers in contact with physiological media exhibit interesting photophysical features, which mimic certain natural photoreceptors, including those in the retina. The availability of such optoelectronic materials opens up a gateway to utilize these structures as neuronal interfaces for stimulating retinal ganglion cells. In a recently reported work entitled “A polymer optoelectronic interface provides visual cues to a blind retina,” we utilized a specific configuration of a polymer semiconductor device structure to elicit neuronal activity in a blind retina upon photoexcitation. The elicited neuronal signals were found to have several features that followed the optoelectronic response of the polymer film. More importantly, the polymer-induced retinal response resembled the natural response of the retina to photoexcitation. These observations open up a promising material alternative for artificial retina applications.     

Carbon‐Coated Li3Nd3W2O12: A High Power and Low‐Voltage Insertion Anode with Exceptional Cycleability for Li‐Ion Batteries

The synthesis of carbon‐coated Li₃Nd₃W₂O₁₂ (C‐Li₃Nd₃W₂O₁₂), a low voltage insertion anode (0.3 V vs. Li) for a Li‐ion battery, is reported to exhibit extraordinary performance. The low voltage reversible insertion provides an increase in the energy density of Li‐ion power packs. For instance, C‐Li₃Nd₃W₂O₁₂ delivered an energy density of ≈390 Wh kg^?1 (based on cathode mass loading) when coupled with an LiMn₂O₄ cathode with an operating potential of 3.4 V. Furthermore, excellent cycling profiles are observed for C‐Li₃Nd₃W₂O₁₂ anodes both in half and full‐cell configurations. The full‐cell is capable of delivering very stable cycling profiles at high current rates (e.g., 2 C), which clearly suggests the high power capability of such garnet‐type anodes.     

Modelling and simulation of porcine liver tissue indentation using finite element method and uniaxial stress–strain data

We hypothesize that both compression and elongation stress–strain data should be considered for modeling and simulation of soft tissue indentation. Uniaxial stress–strain data were obtained from in vitro loading experiments of porcine liver tissue. An axisymmetric finite element model was used to simulate liver tissue indentation with tissue material represented by hyperelastic models. The material parameters were derived from uniaxial stress–strain data of compressions, elongations, and combined compression and elongation of porcine liver samples. in vitro indentation tests were used to validate the finite element simulation. Stress–strain data from the simulation with material parameters derived from the combined compression and elongation data match the experimental data best. This is due to its better ability in modeling 3D deformation since the behavior of biological soft tissue under indentation is affected by both its compressive and tensile characteristics. The combined logarithmic and polynomial model is somewhat better than the 5-constant Mooney–Rivlin model as the constitutive model for this indentation simulation.     

大剂量东菱克栓酶治疗急性脑梗死疗效观察

目的　研究和探讨大剂量东菱克栓酶与常规剂量的治疗效果。　方法　大剂量组 2 0 IU、1 0 IU、1 0 IU连用 3天 ,常规剂量组 1 0 IU、 5IU、 5IU隔日 1次。　结果　大剂量组显效治愈率明显高于常规剂量组 P<0 .0 5,无明显毒副作用。　结论　大剂量东菱克栓酶治疗脑梗死优于常规剂量 ,可缩短病程。     

Anti-apoptotic protein BRE/BRCC45 attenuates apoptosis through maintaining the expression of caspase inhibitor XIAP in mouse Lewis lung carcinoma D122 cells

Brain and Reproductive Organ Expressed (BRE), or BRCC45, is a death receptor-associated antiapoptotic protein, which is also involved in DNA-damage repair, and K63-specific deubiquitination. BRE overexpression attenuates both death receptor- and stress-induced apoptosis, promotes experimental tumor growth, and is associated with human hepatocellular and esophageal carcinoma. How BRE mediates its antiapoptotic function is unknown. Here we report based on the use of a mouse Lewis lung carcinoma cell line D122 that BRE has an essential role in maintaining the cellular protein level of XIAP, which is the most potent endogenous inhibitor of the caspases functioning in both extrinsic and intrinsic apoptosis. shRNA-mediated exhaustive depletion of BRE sensitized D122 cells to apoptosis induced not only by etopoxide, but also by TNF-α even in the absence of cycloheximide, which blocks the synthesis of antiapoptotic proteins by TNF-α-activated NF-κB pathway. In BRE-depleted cells, protein level of XIAP was downregulated, but not the levels of other antiapoptotic proteins, cIAP-1, 2, and cFLIP, regulated by the same NF-κB pathway. Reconstitution of BRE restored XIAP levels and increased resistance to apoptosis. XIAP mRNA level was also reduced in the BRE-depleted cells, but the level of reduction was less profound than that of the protein level. However, BRE could not delay protein turnover of XIAP. Depletion of BRE also increased tumor cell apoptosis, and decreased both local and metastatic tumor growth. Taken together, these findings indicate that BRE and its XIAP-sustaining mechanism could represent novel targets for anti-cancer therapy.     

Apoptosis,cytokine and chemokine induction by non-structural 1 (NS1) proteins encoded by different influenza subtypes

Background

Influenza pandemic remains a serious threat to human health. Viruses of avian origin, H5N1, H7N7 and H9N2, have repeatedly crossed the species barrier to infect humans. Recently, a novel strain originated from swine has evolved to a pandemic. This study aims at improving our understanding on the pathogenic mechanism of influenza viruses, in particular the role of non-structural (NS1) protein in inducing pro-inflammatory and apoptotic responses.

Methods

Human lung epithelial cells (NCI-H292) was used as an in-vitro model to study cytokine/chemokine production and apoptosis induced by transfection of NS1 mRNA encoded by seven infleunza subtypes (seasonal and pandemic H1, H2, H3, H5, H7, and H9), respectively.

Results

The results showed that CXCL-10/IP10 was most prominently induced (> 1000 folds) and IL-6 was slightly induced (< 10 folds) by all subtypes. A subtype-dependent pattern was observed for CCL-2/MCP-1, CCL3/MIP-1α, CCL-5/RANTES and CXCL-9/MIG; where induction by H5N1 was much higher than all other subtypes examined. All subtypes induced a similar temporal profile of apoptosis following transfection. The level of apoptosis induced by H5N1 was remarkably higher than all others. The cytokine/chemokine and apoptosis inducing ability of the 2009 pandemic H1N1 was similar to previous seasonal strains.

Conclusions

In conclusion, the NS1 protein encoded by H5N1 carries a remarkably different property as compared to other avian and human subtypes, and is one of the keys to its high pathogenicity. NCI-H292 cells system proves to be a good in-vitro model to delineate the property of NS1 proteins.

     

Phylogeny and species delineation in the marine diatom Pseudo‐nitzschia (Bacillariophyta) using cox1, LSU,and ITS2 rRNA genes: A perspective in character evolution

Analyses of the mitochondrial cox1, the nuclear‐encoded large subunit (LSU), and the internal transcribed spacer 2 (ITS2) RNA coding region of Pseudo‐nitzschia revealed that the P. pseudodelicatissima complex can be phylogenetically grouped into three distinct clades (Groups I–III), while the P. delicatissima complex forms another distinct clade (Group IV) in both the LSU and ITS2 phylogenetic trees. It was elucidated that comprehensive taxon sampling (sampling of sequences), selection of appropriate target genes and outgroup, and alignment strategies influenced the phylogenetic accuracy. Based on the genetic divergence, ITS2 resulted in the most resolved trees, followed by cox1 and LSU. The morphological characters available for Pseudo‐nitzschia, although limited in number, were overall in agreement with the phylogenies when mapped onto the ITS2 tree. Information on the presence/absence of a central nodule, number of rows of poroids in each stria, and of sectors dividing the poroids mapped onto the ITS2 tree revealed the evolution of the recently diverged species. The morphologically based species complexes showed evolutionary relevance in agreement with molecular phylogeny inferred from ITS2 sequence–structure data. The data set of the hypervariable region of ITS2 improved the phylogenetic inference compared to the cox1 and LSU data sets. The taxonomic status of P. cuspidata and P. pseudodelicatissima requires further elucidation.     

Exploring the effects of different immersion environments on the growth of gold nanostructures

Even though Au crystallizes only as a simple FCC structure in bulk there have been many different and fascinating structures discovered experimentally for Au on the nanoscale. Unfortunately, for Au a direct ab-initio approach in studying dynamic growth mechanisms of nanostructures is prohibitively expensive from a computational perspective, so here we use methods based on accurate semi-empirical, many-body potentials whose parameters are obtained from a combination of empirical and ab-initio data as a viable alternative. We show that this method when combined with molecular dynamics may be used to simulate the growth of Au particles in a bath of solvent atoms (either in a gaseous or liquid state) which results in structures of a range of different morphologies. An analysis of the results indicates what characteristics of the solvent and its interactions are important in determining these different morphologies.