Prevention of Diabetic Nephropathy by Sulforaphane: Possible Role of Nrf2 Upregulation and Activation

The present study was to investigate whether sulforaphane (SFN) can prevent diabetic nephropathy in type 1 diabetic mouse model induced by multiple low-dose streptozotocin. Diabetic and age-matched control mice were given SFN at 0.5 mg/kg body weight daily for 3 months. At the end of 3-month SFN treatment, the diabetic nephropathy, shown by renal inflammation, oxidative damage, fibrosis, and dysfunction, was significantly prevented along with an elevation of renal Nrf2 expression and transcription in diabetes/SFN group compared with diabetic group. However, this renal prevention by SFN was not seen when the 3-month SFN-treated diabetic mice were aged for additional 3 months without further SFN treatment. Nrf2-mediated renal protective effects in diabetes were evaluated in human renal tubular HK11 cells transfected with control and Nrf2 siRNA and treated with 27.5 mM mannitol or high glucose plus palmitate (300 μM). Blockade of Nrf2 expression completely abolished SFN prevention of the profibrotic effect induced by high glucose plus palmitate. These results support that renal Nrf2 expression and its transcription play important roles in SFN prevention of diabetes-induced renal damage. However, the SFN preventive effect on diabetes-induced renal pathogeneses is not sustained, suggesting the requirement of continual use of SFN for its sustained effect

Understanding the function constitution and influence factors on communication for the WeChat official account of top tertiary hospitals in China: Cross-sectional study

Widespread adoption and continued developments in mobile health care technologies have led to the improved accessibility and quality of medical services. In China, WeChat, an instant messaging and social networking app released by the company Tencent, has developed a specific type of user account called WeChat official account (WOA), which is now widely adopted by hospitals in China. It enables health care providers to connect with local citizens, allowing them to, among other actions, send regular updates through mass circulation. However, with the diversity in function provided by WOA, little is known about its major constitution as well as the influence factors on the WeChat communication index (WCI). The WCI has been widely used in social media impact ranking with various types of WeChat content to fully reflect the dissemination and coverage of tweets as well as the maturity and impact of WOA. Objective: There are two typical WOAs available to users, namely, WeChat subscription account (WSSA) and WeChat service account (WSVA). The biggest difference between them is the frequency of messages transmitted. This study aimed to explore the function constitution of WSVA adopted by top tertiary hospitals in China and the major contributors of the WCI score. Methods: A total of 681 top tertiary hospitals were selected from the Hospital Quality Monitoring System; the WOA of every top tertiary hospital was retrieved in the WeChat app. We divided core functional items of WSVAs using categorical principal component analysis. To elicit the factors that influenced the use of WSVA, quantile regression was employed to analyze the WCI score. Results: From the 668 WOAs identified, adoption of WSVAs (543/668, 81.3%) was more than that of WSSAs (125/668, 18.7%). Functional items of WSVAs were categorized into four clusters: (1) hospital introduction, (2) medical services, (3) visiting assistants, and (4) others. With regard to the influence factors on the WCI, the impact of the activity index of WSVA and the total visiting number of outpatients and emergencies on WCI were statistically significant and positive in all quantiles. However, the year of certification, the type of hospital, the year of public hospital reform, and the number of beds merely affected the WCI at some quantiles. Conclusions: Our findings are considered helpful to tertiary hospitals in developing in-depth functional items that improve patient experience. The tertiary hospitals should take full advantage of times of posting and provide high-quality tweets to meet the various needs of patients

Selection of Anti-Sulfadimidine Specific ScFvs from a Hybridoma Cell by Eukaryotic Ribosome Display

BACKGROUND:Ribosome display technology has provided an alternative platform technology for the development of novel low-cost antibody based on evaluating antibiotics derived residues in food matrixes. METHODOLOGY/PRINCIPAL FINDINGS:In our current studies, the single chain variable fragments (scFvs) were selected from hybridoma cell lines against sulfadimidine (SM(2)) by using a ribosome library technology. A DNA library of scFv antibody fragments was constructed for ribosome display, and then mRNA-ribosome-antibody (MRA) complexes were produced by a rabbit reticulocyte lysate system. The synthetic sulfadimidine-ovalbumin (SM(2)-OVA) was used as an antigen to pan MRA complexes and putative scFv-encoding genes were recovered by RT-PCR in situ following each panning. After four rounds of ribosome display, the expression vector pCANTAB5E containing the selected specific scFv DNA was constructed and transformed into Escherichia coli HB2151. Three positive clones (SAS14, SAS68 and SAS71) were screened from 100 clones and had higher antibody activity and specificity to SM(2) by indirect ELISA. The three specific soluble scFvs were identified to be the same molecular weight (approximately 30 kDa) by Western-blotting analysis using anti-E tag antibodies, but they had different amino acids sequence by sequence analysis. CONCLUSIONS/SIGNIFICANCE:The selection of anti-SM(2) specific scFv by in vitro ribosome display technology will have an important significance for the development of novel immunodetection strategies for residual veterinary drugs

Cyclophilin C-associated protein (CyCAP) knock-out mice spontaneously develop colonic mucosal hyperplasia and exaggerated tumorigenesis after treatment with carcinogen azoxymethane1

<p>Abstract</p> <p>Background</p> <p>The discovery of a "serrated neoplasia pathway" has highlighted the role of hyperplastic lesions of the colon as the significant precursor of colorectal adenocarcinoma. In mice, hyperplasia of the colonic mucosa is a regular phenomenon after a challenge with colonic carcinogens indicating that mucosal hyperproliferation and thickening, even without cytological dysplasia, represents an early pre-malignant change. Cyclophilin C-associated protein (CyCAP) has been described to down-modulate endotoxin signaling in colorectal murine mucosa and is a murine orthologue of the tumor-associated antigen 90 K (TAA90K)/mac-2-binding protein.</p> <p>Methods</p> <p>Female Balb/c wild-type (WT) and CyCAP knock-out (KO) mice (6–8 weeks old) were administered 2 or 6 weekly subcutaneous injections of azoxymethane. The animals were evaluated post-injection at six weeks for aberrant crypt foci (ACF) study and at five months for colon tumor measurement. The thickness of the colon crypts was measured in microns and the number of colonocytes per crypt was also determined in well-oriented crypts. Morphometric analyses of the colon mucosa were also performed in untreated 6–8 weeks old KO and WT animals. Formalin-fixed/paraffin-embedded colon sections were also studied by immunohistochemistry to determine the Ki-67 proliferation fraction of the colon mucosa, β-catenin cellular localization, cyclin D1, c-myc, and lysozyme in Paneth cells.</p> <p>Results</p> <p>Cyclophilin C-associated protein (CyCAP)^-/-mice, spontaneously developed colonic mucosal hyperplasia early in life compared to wild-type mice (WT) (p < 0.0001, T-test) and crypts of colonic mucosa of the (CyCAP)^-/-mice show higher proliferation rate (p = 0.039, Mann-Whitney Test) and larger number of cyclin D1-positive cells (p < 0.0001, Mann-Whitney Test). Proliferation fraction and cyclin D1 expression showed positive linear association (p = 0.019, Linear-by-Linear Association). The hyperplasia was even more pronounced in CyCAP^-/-mice than in WT after challenge with azoxymethane (p = 0.005, T-test). The length of the crypts (r = 0.723, p = 0.018, Spearman Correlation) and the number of colonocytes per crypt (r = 0.863, p = 0.001, Spearman Correlation) in non-tumorous areas were positively associated with azoxymethane-induced number of tumors. CyCAP^-/-developed larger numbers of tumors than WT animals (p = 0.003, T-Test) as well as overall larger tumor mass (p = 0.016, T-Test). Membranous β-catenin was focally overexpressed in KO mice including proliferative zone of the crypts.</p> <p>Conclusion</p> <p>CyCAP^-/-represent the first described model of spontaneous colonic mucosal hyperplasia. We conclude that CyCAP-deficient mice spontaneously and after challenge with carcinogen develop significantly more colorectal mucosal hyperplasia, an early stage in murine colonic carcinogenesis.</p

An interlaboratory comparison of aerosol inorganic ion measurements by ion chromatography : Implications for aerosol pH estimate

Water-soluble inorganic ions such as ammonium, nitrate and sulfate are major components of fine aerosols in the atmosphere and are widely used in the estimation of aerosol acidity. However, different experimental practices and instrumentation may lead to uncertainties in ion concentrations. Here, an intercomparison experiment was conducted in 10 different laboratories (labs) to investigate the consistency of inorganic ion concentrations and resultant aerosol acidity estimates using the same set of aerosol filter samples. The results mostly exhibited good agreement for major ions Cl-, SO2-4, NO-3, NHC4 and KC. However, F-, Mg2C and Ca2C were observed with more variations across the different labs. The Aerosol Chemical Speciation Monitor (ACSM) data of nonrefractory SO2-4, NO-3 and NHC4 generally correlated very well with the filter-analysis-based data in our study, but the absolute concentrations differ by up to 42 %. Cl-from the two methods are correlated, but the concentration differ by more than a factor of 3. The analyses of certified reference materials (CRMs) generally showed a good detection accuracy (DA) of all ions in all the labs, the majority of which ranged between 90 % and 110 %. The DA was also used to correct the ion concentrations to showcase the importance of using CRMs for calibration check and quality control. Better agreements were found for Cl-, SO2-4, NO-3, NHC4 and KC across the labs after their concentrations were corrected with DA; the coefficient of variation (CV) of Cl-, SO2-4, NO-3, NHC4 and KC decreased by 1.7 %, 3.4 %, 3.4 %, 1.2 % and 2.6 %, respectively, after DA correction. We found that the ratio of anion to cation equivalent concentrations (AE/CE) and ion balance (anions-cations) are not good indicators for aerosol acidity estimates, as the results in different labs did not agree well with each other. In situ aerosol pH calculated from the ISORROPIA II thermodynamic equilibrium model with measured ion and ammonia concentrations showed a similar trend and good agreement across the 10 labs. Our results indicate that although there are important uncertainties in aerosol ion concentration measurements, the estimated aerosol pH from the ISORROPIA II model is more consistent