BACKGROUND AND AIM: α-complex protein-2 (αCP2) encoded by the poly (rC) binding protein 2(PCBP2) gene is responsible for the accumulation of type I collagen in fibrotic livers. In this study, we silenced the PCBP2 gene using a small interfering RNA (siRNA) to reverse alcohol-and cytokine-induced profibrogenic effects on hepatic stellate cells (HSCs). METHODS: Primary rat HSCs and the HSC-T6 cell line were used as fibrogenic models to mimic the initiation and perpetuation stages of fibrogenesis, respectively. We previously found that a PCBP2 siRNA, which efficiently silences expression of αCP2, reduces the stability of type I collagen mRNA. We investigated the effects of the PCBP2 siRNA on cell proliferation and migration. Expression of type I collagen in HSCs was analyzed by quantitative real-time PCR and western blotting. In addition, we evaluated the effects of the PCBP2 siRNA on apoptosis and the cell cycle. RESULTS: PCBP2 siRNA reversed multiple alcohol- and cytokine-induced profibrogenic effects on primary rat HSCs and HSC-T6 cells. The PCBP2 siRNA also reversed alcohol- and cytokine-induced accumulation of type I collagen as well as cell proliferation and migration. Moreover, the combination of LY2109761, a transforming growth factor-β1 inhibitor, and the PCBP2 siRNA exerted a synergistic inhibitive effect on the accumulation of type I collagen in HSCs. CONCLUSIONS: Silencing of PCBP2 using siRNA could be a potential therapeutic strategy for alcoholic liver fibrosis.

Background and aim

α-complex protein-2 (αCP2) encoded by the poly (rC) binding protein 2(PCBP2) gene is responsible for the accumulation of type I collagen in fibrotic livers. In this study, we silenced the PCBP2 gene using a small interfering RNA (siRNA) to reverse alcohol-and cytokine-induced profibrogenic effects on hepatic stellate cells (HSCs).

Methods

Primary rat HSCs and the HSC-T6 cell line were used as fibrogenic models to mimic the initiation and perpetuation stages of fibrogenesis, respectively. We previously found that a PCBP2 siRNA, which efficiently silences expression of αCP2, reduces the stability of type I collagen mRNA. We investigated the effects of the PCBP2 siRNA on cell proliferation and migration. Expression of type I collagen in HSCs was analyzed by quantitative real-time PCR and western blotting. In addition, we evaluated the effects of the PCBP2 siRNA on apoptosis and the cell cycle.

Results

PCBP2 siRNA reversed multiple alcohol- and cytokine-induced profibrogenic effects on primary rat HSCs and HSC-T6 cells. The PCBP2 siRNA also reversed alcohol- and cytokine-induced accumulation of type I collagen as well as cell proliferation and migration. Moreover, the combination of LY2109761, a transforming growth factor-β1 inhibitor, and the PCBP2 siRNA exerted a synergistic inhibitive effect on the accumulation of type I collagen in HSCs.

Conclusions

Silencing of PCBP2 using siRNA could be a potential therapeutic strategy for alcoholic liver fibrosis.

Miscanthus giganteus (M. giganteus) is a promising feedstock for the production of bioethanol or biochemicals. Using only dilute nitric acid, this work describes a two-step process for hydrolyzing hemicellulose and cellulose to fermentable sugars. Primary variables were temperature and reaction time. The solid-to-liquid mass ratio was 1:8. No enzymes were used. In the first step, M. giganteus was contacted with 0.5 wt.% nitric acid at temperatures between 120 and 160°C for 5 to 40 min. The second step used 0.5 or 0.75 wt.% nitric acid at temperatures between 180 and 210°C for less than 6 min. Under selected conditions, almost all hemicellulose and 58% cellulose were transferred to the liquid phase. Small amounts of degradation products were observed. The xylose solution obtained from the nitric-acid hydrolysis was fermented for 96 h and the glucose solution for 48 h to yield 0.41 g ethanol/g xylose and 0.46 g ethanol/g glucose. To characterize residual solids and the liquor from both steps, nuclear-magneticresonance (NMR) spectroscopy was performed for each fraction. The analytical data indicate that the liquid phase from Steps 1 and 2 contain little lignin or lignin derivatives.

Particle collisions at the energy frontier can probe the nature of invisible dark matter via production in association with recoiling visible objects. We propose a new potential production mode, in which dark matter is produced by the decay of a heavy dark Higgs boson radiated from a heavy W′ boson. In such a model, motivated by left-right symmetric theories, dark matter would not be pair produced in association with other recoiling objects due to its lack of direct coupling to quarks or gluons. We study the hadronic decay mode via W′ → tb and estimate the LHC exclusion sensitivity at 95% confidence level to be 102 − 105 fb for W′ boson masses between 250 and 1750 GeV.

Pretreatment of miscanthus is essential for enzymatic production of sugars to yield bioethanol. A two-step process using 10 wt % aqueous ammonia in the first step is followed by 1 wt % sodium hydroxide (with or without oxygen or 1 wt % hydrogen peroxide) in the second step. The first step retains about 90% of the cellulose and about 67% of the hemicellulose in the solid while removing about 62% of the lignin. Both steps together achieve 83-90% delignification. Subsequent enzymatic conversion to fermentable sugars is close to 90% after 96 h. While an oxidant does not significantly increase delignification, it has a favorable effect on saccharification of the recovered solid. Infrared spectroscopy, X-ray diffraction, and two-dimensional nuclear magnetic resonance spectroscopy provide data concerning the chemical composition of the recovered solid. Inclusion of an oxidant to the pretreatment breaks β-O-4′- linked aryl ether bonds of the remaining lignin in the recovered solid. © 2013 American Chemical Society.

This special issue provides an assessment of the contribution of soils to Nature's Contributions to People (NCP). Here, we combine this assessment and previously published relationships between NCP and delivery on the UN Sustainable Development Goals (SDGs) to infer contributions of soils to the SDGs. We show that in addition to contributing positively to the delivery of all NCP, soils also have a role in underpinning all SDGs. While highlighting the great potential of soils to contribute to sustainable development, it is recognized that poorly managed, degraded or polluted soils may contribute negatively to both NCP and SDGs. The positive contribution, however, cannot be taken for granted, and soils must be managed carefully to keep them healthy and capable of playing this vital role. A priority for soil management must include: (i) for healthy soils in natural ecosystems, protect them from conversion and degradation; (ii) for managed soils, manage in a way to protect and enhance soil biodiversity, health and sustainability and to prevent degradation; and (iii) for degraded soils, restore to full soil health. We have enough knowledge now to move forward with the implementation of best management practices to maintain and improve soil health. This analysis shows that this is not just desirable, it is essential if we are to meet the SDG targets by 2030 and achieve sustainable development more broadly in the decades to come. This article is part of the theme issue 'The role of soils in delivering Nature's Contributions to People'.