Ischaemic post-conditioning protects lung from ischaemia-reperfusion injury by up-regulation of haeme oxygenase-1

Objective: The emergence of ischaemic post-conditioning (IPO) provides a potential method for experimentally and clinically attenuating various types of organ injuries. There has been little work, however, examining its effects in the setting of lung ischaemia reperfusion (IR). The stress protein, haeme oxygenase-1 (HO-1), has been found to exert a potent, protective role in a variety of lung injury models. In this study, we hypothesised that the induction of HO-1 by IPO plays a protective role against the deleterious effects of IR in the lung. Methods: Anaesthetised and mechanically ventilated adult Sprague-Dawley rats were randomly assigned to one of the following groups (n = 8 each): the sham-operated control group, the IR group (40 min of left-lung ischaemia and 105 min of reperfusion), the IPO group (three successive cycles of 30-s reperfusion per 30-s occlusion before restoring full perfusion) and the ZnPPIX + IPO group (ZnPPIX, an inhibitor of HO-1, was injected intra-peritoneally at 20 mg kg -1 24 h prior to the experiment and the rest of the procedures were similar to that of the IPO group). Lung injury was assessed by arterial blood gas analysis, wet-to-dry lung weight ratio and tissue histological changes. The extent of lipid peroxidation was determined by measuring plasma levels of malondialdehyde (MDA) production. Expression of HO-1 was determined by immunohistochemistry. Results: Lung IR resulted in a significant reduction of PaO 2 (data in IR, P < 0.05 vs. data in sham) and increase of lung wet-to-dry weight ratio, accompanied with increased MDA production and severe lung pathological morphological changes as well as a compensatory increase in HO-1 protein expression, as compared with sham (All P < 0.05). IPO markedly attenuated all the above pathological changes seen in the IR group and further increased HO-1 expression. Treatment with ZnPPIX abolished all the protective effects of post-conditioning. Conclusion: It may be concluded that IPO protects IR-induced lung injury via induction of HO-1. © 2009 Elsevier Ltd. All rights reserved.postprin

Ellagic acid, a phenolic compound, exerts anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer

Anti-angiogenesis targeting VEGFR-2 has been considered as an important strategy for cancer therapy. Ellagic acid is a naturally existing polyphenol widely found in fruits and vegetables. It was reported that ellagic acid interfered with some angiogenesis-dependent pathologies. Yet the mechanisms involved were not fully understood. Thus, we analyzed its anti-angiogenesis effects and mechanisms on human breast cancer utilizing in-vitro and in-vivo methodologies. The in-silico analysis was also carried out to further analyze the structure-based interaction between ellagic acid and VEGFR-2. We found that ellagic acid significantly inhibited a series of VEGF-induced angiogenesis processes including proliferation, migration, and tube formation of endothelial cells. Besides, it directly inhibited VEGFR-2 tyrosine kinase activity and its downstream signaling pathways including MAPK and PI3K/Akt in endothelial cells. Ellagic acid also obviously inhibited neo-vessel formation in chick chorioallantoic membrane and sprouts formation of chicken aorta. Breast cancer xenografts study also revealed that ellagic acid significantly inhibited MDA-MB-231 cancer growth and P-VEGFR2 expression. Molecular docking simulation indicated that ellagic acid could form hydrogen bonds and aromatic interactions within the ATP-binding region of the VEGFR-2 kinase unit. Taken together, ellagic acid could exert anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer. © 2012 The Author(s).published_or_final_versio

Stepwise photoassisted decomposition of carbohydrates to H2

Biomass reforming by harvesting solar energy can provide green hydrogen. Current biomass photoreforming provides H2 erratically and in limited yield although efficiently, owing to intermittent features of solar light and incomplete degradation of biomass C-C bonds. Here, we detour the flaws by prioritizing conversion of carbohydrates to liquid hydrogen carriers (LHCs, consisting of HCOOH and HCHO), appropriate for transportation. Subsequently, the LHCs are fully decomposed, releasing only H-2 and CO2. This stepwise process enables complete scission of carbohydrate C-C bonds, affording 44 g of H-2 per kg of glucose thereof. Intermittent solar light provides the photoenergy and heat to split glucose car-bons to produce LHCs (2.5 mmol h(-1)) in a flow apparatus. This work demonstrates hydrogen production and storage by empha-sizing the complete scission of biomass C-C bonds

SUMO-2 promotes mRNA translation by enhancing interaction between eIF4E and eIF4G

Small ubiquitin-like modifier (SUMO) proteins regulate many important eukaryotic cellular processes through reversible covalent conjugation to target proteins. In addition to its many well-known biological consequences, like subcellular translocation of protein, subnuclear structure formation, and modulation of transcriptional activity, we show here that SUMO-2 also plays a role in mRNA translation. SUMO-2 promoted formation of the active eukaryotic initiation factor 4F (eIF4F) complex by enhancing interaction between Eukaryotic Initiation Factor 4E (eIF4E) and Eukaryotic Initiation Factor 4G (eIF4G), and induced translation of a subset of proteins, such as cyclinD1 and c-myc, which essential for cell proliferation and apoptosis. As expected, overexpression of SUMO-2 can partially cancel out the disrupting effect of 4EGI-1, a small molecule inhibitor of eIF4E/eIF4G interaction, on formation of the eIF4F complex, translation of the cap-dependent protein, cell proliferation and apoptosis. On the other hand, SUMO-2 knockdown via shRNA partially impaired cap-dependent translation and cell proliferation and promoted apoptosis. These results collectively suggest that SUMO-2 conjugation plays a crucial regulatory role in protein synthesis. Thus, this report might contribute to the basic understanding of mammalian protein translation and sheds some new light on the role of SUMO in this process. © 2014 Chen et al

Down-regulated CK8 expression in human intervertebral disc degeneration

As an intermediate filament protein, cytokeratin 8 (CK8) exerts multiple cellular functions. Moreover, it has been identified as a marker of notochord cells, which play essential roles in human nucleus pulposus (NP). However, the distribution of CK8 positive cells in human NP and their relationship with intervertebral disc degeneration (IDD) have not been clarified until now. Here, we found the percentage of CK8 positive cells in IDD (25.7+/-4.14%) was significantly lower than that in normal and scoliosis NP (51.9+/-9.73% and 47.8+/-5.51%, respectively, p<0.05). Western blotting and qRT-PCR results confirmed the down-regulation of CK8 expression in IDD on both of protein and mRNA levels. Furthermore, approximately 37.4% of cell clusters were CK8 positive in IDD. Taken together, this is the first study to show a down-regulated CK8 expression and the percentage of CK8 positive cell clusters in IDD based upon multiple lines of evidence. Consequently, CK8 positive cells might be considered as a potential option in the development of cellular treatment strategies for NP repair.published_or_final_versio

Early Detection of Ovarian Cancer in Samples Pre-Diagnosis Using CA125 and MALDI-MS Peaks

Aim: A nested case-control discovery study was undertaken 10 test whether information within the serum peptidome can improve on the utility of CA125 for early ovarian cancer detection. Materials and Methods: High-throughput matrix-assisted laser desorption ionisation mass spectrometry (MALDI-MS) was used to profile 295 serum samples from women pre-dating their ovarian cancer diagnosis and from 585 matched control samples. Classification rules incorporating CA125 and MS peak intensities were tested for discriminating ability. Results: Two peaks were found which in combination with CA125 discriminated cases from controls up to 15 and 11 months before diagnosis, respectively, and earlier than using CA125 alone. One peak was identified as connective tissue-activating peptide III (CTAPIII), whilst the other was putatively identified as platelet factor 4 (PF4). ELISA data supported the down-regulation of PF4 in early cancer cases. Conclusion: Serum peptide information with CA125 improves lead time for early detection of ovarian cancer. The candidate markers are platelet-derived chemokines, suggesting a link between platelet function and tumour development

Novel insights into the hallmarks of human nucleus pulposus cells with particular reference to cell viability, phagocytic potential and long process formation

General Posters: no. GP88INTRODUCTIONS: As a main cellular component within the disc, nucleus pulposus (NP) cells play important roles in disc physiology. However, little is known on the biologic hallmarks of human NP cells. Therefore, the present study aimed to address the features of human NP ...postprin

CK8 phosphorylation induced by compressive loads underlies the downregulation of CK8 in human disc degeneration by activating protein kinase C

Cytokeratin 8 (CK8) is a member of the cytokeratins family with multiple functions on the basis of its unique structural hallmark. The aberrant expression of CK8 and its phosphorylation are pertinent with various diseases. We have previously shown that CK8 exists in normal human nucleus pulposus (NP) cells and decreases as the intervertebral disc degenerates. However, the underlying molecular regulatory machinery of CK8 in intervertebral disc degeneration (IDD) has not been clarified. Here, we collected NP samples from patients with idiopathic scoliosis as control and IDD as degenerate groups. We found that CK8 expression decreased in IDD with an increased phosphorylation in degenerate NP cells. Moreover, NP cells were cultured under different compressive load schemes for diverse time duration. We found that compressive loads resulted in phosphorylation and disassembly of CK8 in a time-dependent and degree-dependent manner in vitro. The activation of protein kinase C was a significant molecular factor contributing to this phenomenon. Taken together, this study is the first to address the molecular mechanisms of CK8 downregulation in NP cells. Importantly, our findings provide clues regarding a molecular link between compressive loads and CK8 alterations, which shed a novel light on the etiology of IDD.published_or_final_versio

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

Three-dimensional micromachining for microsystems by confined etchant layer technique

The micromachining of GaAs with three different truly three-dimensional (3D) molds were performed by the confined etchant layer technique (CELT). The etched patterns were found, approximately, to be the negative copy of the 3D molds. The general comparison of CELT with the existing micromachining techniques, such as two-dimensional (2D) projection lithography and electro-discharge machining, was made. The replication of the complex microstructures down to micrometer scale has been done by CELT in a single step. The photoresist layer, together with the procedures of exposure, developing and removal of resist, could be eliminated. The advantages of CELT over the existing lithography techniques and its potential applications are discussed briefly. It has been shown that CELT could be developed as a complementary technique to the existing micromachining techniques in fabricating microdevices for microsystems. (C) 2001 Elsevier Science Ltd. All rights reserved