Effect of heparin on high glucose induced proliferation and expression of matrix metalloproteinases in normal human mesangial cells

Background The pathogenesis of diabetic nephropathy (DN) is a complex pathophysiological process. Its precise mechanism is not fully known. In recent years it has been recognized that synthesis of various extracelluar matrix (ECM) components may increase, and that degradation of ECM may decrease in DN. It was reported heparin could inhibit mesangial cells proliferation in vitro. The main aim of this study is to explore whether heparin inhibits proliferation of mesangial cells grown in high glucose concentration and to measure the effect of heparin on matrix metalloproteinases (MMPs) expression in mesangial cells. Methods The medium contained either low glucose (5 mmol/L) or high glucose (25 mmol/L). The concentrations of heparin in the culture medium were 0, 25, 50, 100, 200 or 400 μg/mL. A metabolic (WST-1) assay was used to measure mesangial cell proliferation and Western blot analysis was used to measure MMPs expression of mesangial cells. Results Normal human mesangial cell (NHMC) proliferation was higher in high glucose (HG) medium than in low glucose (LG) medium. They showed a 1.93 fold expansion after 72 h in high glucose in contrast to a 1.63 fold expansion in low glucose. In the presence of heparin, mesangial cells proliferation was inhibited, which was more obvious at high glucose concentrations than at low glucose concentrations. In high glucose, with heparin concentration of 50, 100, 200 and 400 μg/mL, the mesangial cells showed a 0.61 fold, 0.52 fold, 0.52 fold and 0.41 fold reductions in cell number compared to cells grown without heparin. In low glucose, only concentrations of 200 μg/mL and 400 μg/mL showed reduction in cell number, namely 0.54 fold and 0.45 fold, when compared to cells grown without heparin. In Western blot analysis, MMP₁, MMP₂, MMP₃ and MMP₉ was expressed by mesangial cells expressed in both high and low glucose concentrations, which was more prominent in high glucose medium. Incubation of heparin further increased expression of MMP₁, MMP₂, MMP₃ and MMP₉. Conclusions This study suggests that glucose can accelerate mesangial cell proliferation while heparin can reduce proliferation, being more obvious at high glucose concentrations. Higher glucose concentrations led to increased MMP expression, which may take part in the regulation of mesangial matrix synthesis and degradation. Addition of heparin resulted in a corresponding increase in MMP expression, most notably at high glucose concentrations, indicating a potentially renoprotective role in DN. Foundation item: Project (30370663) supported by the National Natural Science Foundation of China     

Possible Involvement of the Upregulation of ΔNp63 Expression Mediated by HER2-Activated Aryl Hydrocarbon Receptor in Mammosphere Maintenance

Cancer stem cells (CSCs) contribute to the drug resistance, recurrence, and metastasis of breast cancers. Recently, we demonstrated that HER2 overexpression increases mammosphere formation via the activation of aryl hydrocarbon receptor (AHR). In this study, the objective was to identify the mechanism underlying mammosphere maintenance mediated by HER2 signaling-activated AHR. We compared the chromatin structure of AHR-knockout (AHRKO) HER2-overexpressing MCF-7 (HER2-5) cells with that of wild-type HER2-5 cells; subsequently, we identified TP63, a stemness factor, as a potential target gene of AHR. ΔNp63 mRNA and protein levels were higher in HER2-5 cells than in HER2-5/AHRKO cells. Activation of HER2/HER3 signaling by heregulin treatment increased ΔNp63 mRNA levels, and its induction was decreased by AHR knockdown in HER2-5 cells. The results of the chromatin immunoprecipitation assay revealed an interaction between AHR and the intronic region of TP63, which encodes ΔNp63. A luciferase reporter gene assay with the intronic region of TP63 showed that AHR expression increased reporter activity. Collectively, our findings suggest that HER2-activated AHR upregulates ΔNp63 expression and that this signaling cascade is involved in CSC maintenance in HER2-expressing breast cancers.     

Chiral lewis acid-catalyzed enantioselective michael reactions in water

Asymmetric Michael reactions of ß-ketoesters with enones were effectively catalyzed by complexes of silver salts and BINAP derivatives in water. The reactions have proved to give Michael adducts in high yields with high enantioselectivities. These reactions are the first example of Lewis acid-catalyzed asymmetric Michael reactions in water.     

Separation of C6H6 and C6H12 from H2 using ionic liquid/PVDF composite membrane

Ionic liquid/polyvinylidene fluoride composite membrane was successfully prepared by impregnation method and used for the separation on organic chemical hydride process. The separation factors of C₆H₆/H₂ and C₆H₁₂/H₂ in the ternary mixture system were 7500 and 300, respectively. The ionic liquid membrane showed an excellent possibility as a technology of H₂ purification in the organic chemical hydride process by removing aromatic hydrocarbon and cycloalkane simultaneously from the ternary system. © 2015 American Institute of Chemical Engineers AIChE J, 62: 624–628, 2016     

Development of Fluorogenic Probes for Rapid High-Contrast Imaging of Transient Nuclear Localization of Sirtuin 3

Protein labeling using fluorogenic probes enables the facile visualization of proteins of interest. Herein, we report new fluorogenic probes consisting of a rationally designed coumarin ligand for the live-cell fluorogenic labeling of the photoactive yellow protein (PYP)-tag. On the basis of the photochemical mechanisms of coumarin and the probe–tag interactions, we introduced a hydroxy group into an environment-sensitive coumarin ligand to modulate its spectroscopic properties and increase the labeling reaction rate. The resulting probe had a higher labeling reaction rate constant and a greater fluorescence OFF–ON ratio than any previously developed PYP-tag labeling probe. The probe enabled the fluorogenic labeling of intracellular proteins within minutes. Furthermore, we used our probe to investigate the localization of sirtuin 3 (SIRT3), a mitochondrial deacetylase. Although the nuclear localization of SIRT3 has been controversial, this transient nuclear localization was clearly captured by the rapid, high-contrast imaging enabled by our probe.     

Understanding the local reality of the adoption of sustainable practices and farmer livelihoods: the case of pummelo farming in Chaiyaphum, Northeast Thailand

In the light of the serious economic crisis of 1997 and Agenda 21, as proposed in the United Nations Conference on Environment and Development in 1992, the Thai government has increased commitments to sustainable agricultural development. This paper examines how local Thai farmers are interacting with the policy imperatives of sustainable agriculture, focusing on the adoption of sustainable practices and farmer livelihoods. Two pummelo producing communities in Chaiyaphum province, Northeast Thailand were chosen as examples and compared: one, located in the highlands, focused on sales for local and domestic markets and the other, located in the lowlands, included sales for export. Both were involved in the implementation of Q-GAP, a public policy for good agricultural practices. The pummelo producers discursively sought the best combination of conventional and sustainable farming practices by balancing the benefits and risks concerning labour requirements, commercial results, financial risks associated with credit loans and investment and ecological sustainability.     

Photocatalytic decomposition of gaseous HCHO over a titanium dioxide film formed on a hydrophobic PET sheet

BACKGROUND: The authors (Chem Eng J 148, 234 (2009)) previously demonstrated the excellent performance of a photocatalytic reactor with a parallel array of nine light sources. To enhance the possibility of practical application of this reactor, the present work explores the use of a PET (polyethylene terephthalate) sheet as a new cheap material to support TiO₂, as an alternative to glass tubes. A method of coating the hydrophobic PET sheet with a TiO₂ film using an aqueous coating solution is investigated and the performance of the TiO₂‐PET sheet prepared evaluated. RESULTS: The affinity of the coating solution for the PET sheet is greatly enhanced by addition of 0.01% (w/w) nonionic surfactant (polyoxyethylene lauryl ether). A relatively uniform thin TiO₂ film is formed on the entire surface of the PET sheet by applying the coating solution to the PET sheet and drying it at 100 °C. Decomposition experiments of gaseous HCHO indicate that the photocatalytic activity, although initially low, is increased with repeated use. This is because surfactant molecules added interfere initially with the decomposition of HCHO. After their decomposition, the TiO₂–PET sheet decomposes HCHO at almost the same rate as does the TiO₂–glass tube. CONCLUSION: The photocatalytic reactor with a parallel array of nine light sources can utilize a PET sheet as TiO₂ support with a reduction in material cost. Copyright © 2011 Society of Chemical Industry     

Modeling Party Support of Japanese Voters in the Early 1996

This article investigates factors that influenced Japanese voters in the early 1996 in determining which political party to support. Proportional-odds model, a model which retains ordinal nature of political hues or ideologies of the Japanese political parties, is fitted to the data. Samples with answers “I do not know” to the questions are treated as missing. The EM algorithm enables us to incorporate the samples with missing-values. We found that determining which party to support is a purely political decision for Japanese voters based solely on their ideologies and attitude towards the current cabinet, not to be influenced by their geographical profiles nor financial situations. Missing-value problem were found not to be ignored in the sense that marginally significant or insignificant explanatory variables can easily turn otherwise when the same model is fitted only for the data with no missing-values.