Angiotensin II mediates the high-glucose-induced endothelial-to-mesenchymal transition in human aortic endothelial cells

<p>Abstract</p> <p>Background</p> <p>Substantial evidence suggests that high glucose (HG) causes endothelial cell damage; however, the potential mechanism therein has yet to be clarified. The aim of this study was to investigate the influence of HG on the endothelial-to-mesenchymal transition (EndMT) and its relevance to the activation of the renin-angiotensin system.</p> <p>Methods</p> <p>Primary human aortic endothelial cells (HAECs) were divided into three groups: a normal glucose (NG) group, HG group, and irbesartan (1 μM)-treated (HG+irbesartan) group. The concentration of angiotensin II in the supernatant was detected by radioimmunoassay. Pathological changes were investigated using fluorescence microscopy and electron microscopy. Immunofluorescence staining was performed to detect the co-expression of CD31 and fibroblast markers, such as fibroblast-specific protein 1 (FSP1). The expressions of FSP1 and α-SMA were detected by RT-PCR and Western blot.</p> <p>Results</p> <p>The treatment of HAECs in the HG group resulted in significant increases in the expressions of FSP1 and angiotensin II in dose-and time-dependent manners. The incubation of HAECs exposure to HG resulted in a fibroblast-like phenotype, wherein increased microfilamentation and a roughened endoplasmic reticulum structure were observed in the cytoplasm. The expressions of FSP1 and α-SMA were significantly increased in the HG group, and these changes were inhibited by irbesartan treatment (<it>P </it>< 0.05). Double staining of the HAECs indicated a co-localization of CD31 and FSP1 and that some cells acquired spindle-shaped morphologies and a loss of CD31 staining; however, treatment with irbesartan attenuated the expression of EndMT (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>These findings suggest a novel mechanism in HG-induced endothelial damage via the mediation of the EndMT by angiotensin II, which was inhibited by Irbesartan.</p

Magnesium intake, plasma C-peptide, and colorectal cancer incidence in US women: a 28-year follow-up study

Background: Laboratory studies suggest a possible role of magnesium intake in colorectal carcinogenesis but epidemiological evidence is inconclusive. Method: We tested magnesium–colorectal cancer hypothesis in the Nurses' Health Study, in which 85 924 women free of cancer in 1980 were followed until June 2008. Cox proportional hazards regression models were used to estimate multivariable relative risks (MV RRs, 95% confidence intervals). Results: In the age-adjusted model, magnesium intake was significantly inversely associated with colorectal cancer risk; the RRs from lowest to highest decile of total magnesium intake were 1.0 (ref), 0.93, 0.81, 0.72, 0.74, 0.77, 0.72, 0.75, 0.80, and 0.67 (Ptrend<0.001). However, in the MV model adjusted for known dietary and non-dietary risk factors for colorectal cancer, the association was significantly attenuated; the MV RRs were 1.0 (ref), 0.96, 0.85, 0.78, 0.82, 0.86, 0.84, 0.91, 1.02, and 0.93 (Ptrend=0.77). Similarly, magnesium intakes were significantly inversely associated with concentrations of plasma C-peptide in age-adjusted model (Ptrend=0.002) but not in multivariate-adjusted model (Ptrend=0.61). Results did not differ by subsite or modified by calcium intakes or body mass index. Conclusion: These prospective results do not support an independent association of magnesium intake with either colorectal cancer risk or plasma C-peptide levels in women

Experimental research on the volatilization and condensation of ammonium bisulfate as SCR byproduct

In this paper, the research progress of ammonium bisulfate (ABS) volatilization in coal-fired power plants the SCR denitrification process was reviewed. Combination with self-made experiments, SEM, flue gas analyzer and TG-DTG curves of ABS and ion chromatography. The volatilization and condensation characteristics of ABS were investigated carefully. Results show that as the temperature increased by 50 °C, the ABS/AS volatilization rate increased by an order of magnitude. The decomposition process of ABS should have a two-step reaction. The reaction in the initial volatilization stage is ABS dehydration turned into (NH4)2S2O7. The reaction in the rapid volatilization stage is (NH4)2S2O7 decomposed into NH3, N2, SO2 and H2O. There is an inter-section in the reac-tion temperature range (especially 300 °C) between the two-step reaction. This research provides an experimental basis for temperature control of ABS to avoid air pre-heater fouling

Bacteriocins: Potential for Human Health

Due to the challenges of antibiotic resistance to global health, bacteriocins as antimicrobial compounds have received more and more attention. Bacteriocins are biosynthesized by various microbes and are predominantly used as food preservatives to control foodborne pathogens. Now, increasing researches have focused on bacteriocins as potential clinical antimicrobials or immune-modulating agents to fight against the global threat to human health. Given the broad- or narrow-spectrum antimicrobial activity, bacteriocins have been reported to inhibit a wide range of clinically pathogenic and multidrug-resistant bacteria, thus preventing the infections caused by these bacteria in the human body. Otherwise, some bacteriocins also show anticancer, anti-inflammatory, and immune-modulatory activities. Because of the safety and being not easy to cause drug resistance, some bacteriocins appear to have better efficacy and application prospects than existing therapeutic agents do. In this review, we highlight the potential therapeutic activities of bacteriocins and suggest opportunities for their application

Bovicin HJ50-Like Lantibiotics, a Novel Subgroup of Lantibiotics Featured by an Indispensable Disulfide Bridge

<div><p>Lantibiotics are ribosomally-synthesized and posttranslationally modified peptides with potent antimicrobial activities. Discovery of novel lantibiotics has been greatly accelerated with the soaring release of genomic information of microorganisms. As a unique class II lantibiotic, bovicin HJ50 is produced by <i>Streptococcus bovis</i> HJ50 and contains one rare disulfide bridge. By using its precursor BovA as a drive sequence, 16 BovA-like peptides were revealed in a wide variety of species. From them, three representative novel <i>lan</i> loci from <i>Clostridium perfringens</i> D str. JGS1721, <i>Bacillus cereus</i> As 1.348 and <i>B. thuringiensis</i> As 1.013 were identified by PCR screening. The corresponding mature lantibiotics designated perecin, cerecin and thuricin were obtained and structurally elucidated to be bovicin HJ50-like lantibiotics especially by containing a conserved disulfide bridge. The disulfide bridge was substantiated to be essential for the function of bovicin HJ50-like lantibiotics as its disruption eliminated their antimicrobial activities. Further analysis indicated that the disulfide bridge played a crucial role in maintaining the hydrophobicity of bovicin HJ50, which might facilitate it to exert antimicrobial function. This study unveiled a novel subgroup of disulfide-containing lantibiotics from bacteria of different niches and further demonstrated the indispensable role of disulfide bridge in these novel bovicin HJ50-like lantibiotics.</p></div

Comparison of hydrophobicity of bovicin HJ50 and its mutants by ANS binding analysis.

<p>Bovicin HJ50 (black curve), its reduced form (blue) and mutant C21A (red). H₂O was used as negative control (green).</p

MS analysis and IC₅₀ determination of bovicin HJ50-like lantibiotics.

a<p>Calculated molecular weight (MW) of protonated peptides.</p>b<p>Post translational modification.</p>c<p>The 50% inhibitory concentration.</p

Structure and antimicrobial activity of bovicin HJ50-like lantibiotics.

<p>(A) Comparison of structure of bovicin HJ50-like lantibiotics with lacticin 481. Gray residues indicated identical amino acids and the Cys residues in red of yellow background indicated disulfide-forming Cys in bovicin HJ50, suicin, perecin, cerecin and thuricin. (B) Comparison of antimicrobial activity of bovicin HJ50-like lantibiotics. In each hole, 25 µL of 10 µg/mL compounds were applied.</p

MS analysis and IC₅₀ determination of ring C mutants of bovicin HJ50.

a<p>C-s, C-p, C-c and C-PG respectively represents the mutant of substitution of c ring of bovicin HJ50 by the counterpart of suicin, perecin, cerecin and ProGly.</p>b<p>No antimicrobial activity detected.</p

Mutation, substitution and alkylation of disulfide bridge in bovicin HJ50-like lantibiotics.

<p>(A) Antimicrobial activity of wild type bovicin HJ50 (25 µL, 5 µg/mL) when treated respectively with 0, 2, 4, 8 mM TCEP. (B) MS analysis of purified NEM-alkylated bovicin HJ50. (C) Antimicrobial activity of wild type bovicin HJ50 (WT) and alkylated bovicin HJ50 (WT-NEM). (D) Antimicrobial activity of disulfide-related mutants. D/K represents substitution of disulfide-forming Cys residues to Asp and Lys, e.g., bovicin HJ50 D/K means bovicin HJ50 mutant C21D/C29K. L/L or F/F is referred as the same condition as D/K. 25 µL peptide samples of 20 µg/mL were applied to each hole.</p