Resveratrol Nanoparticles Suppresses Migration and Invasion of Renal Cell Carcinoma Cells by Inhibiting Matrix Metalloproteinase 2 Expression and Extracellular Signal-Regulated Kinase Pathway.

The aim of this study was to examine the impact of Resveratrol nanoparticles on migration/invasion capacity of renal cell carcinoma (RCC) cells and its mechanism. Human RCC cells were exposed to dimethyl sulfoxide or gradient concentrations of Resveratrol nanoparticles respectively, and U0126 were also added in some experiments. We examined renal cell viability by MTT assay, and wound healing test and Transwell assays were used detect invasion and migration capability of RCC cells. We used Western blotting assay to analyze the protein levels in extracellular signal-regulated kinase (ERK) signaling. We also detected the enzymatic capacity of matrix metalloproteinase 2 (MMP-2) in cells by gelatin enzymatic profiling. Resveratrol nanoparticles treatment significantly suppressed cell viability to migrate and invade RCC cells in a dose-dependent manner. Also, notably were reduced MMP-2 activity and expression, and elevated TIMP-2 level were observed in RCC cells exposed with Resveratrol nanoparticles. Further, Resveratrol nanoparticles treatment significantly decreased only the expression of p-ERK1/2, but not p-p38 and p-JNK. Moreover, U0126, which is the ERK inhibitor, exerted similar role as Resveratrol nanoparticles did. Of note was that, combined use of U0126 and Resveratrol nanoparticles displayed a more intense suppression of MMP-2 activity and expression, and also the viability to migrate and invade the RCC cells, compared with Resveratrol nanoparticles treatment alone. The Resveratrol nanoparticles inhibited RCC cells migration and invasion by regulating MMP2 expression and ERK pathways.

Association of Megsin Gene Variants With IgA Nephropathy in Northwest Chinese Population: A STROBE-Compliant Observational Study.

Megsin is a mesangial cell-predominant gene that encodes a serpin family protein which is expressed in the renal mesangium. Overexpression of megsin has been observed in the glomeruli of patients with IgA nephropathy (IgAN). The aim of this study was to evaluate the association of megsin polymorphisms (rs1055901 and rs1055902) with IgAN in a Chinese population.We examined 351 patients with histologically proven IgAN and compared them with 310 age, sex, and ethnicity-matched healthy subjects. Two single nucleotide polymorphisms (SNPs) in megsin were genotyped by Sequenom MassARRAY. SPSS 18.0 was used for statistical analyses, and SNP Stats to test for associations between these polymorphisms and IgAN risk. Odds ratios with 95% confidence intervals were used to assess the relationships.We found that rs1055901 and rs1055902 SNPs were not correlated with susceptibility to IgAN in Northwest Chinese population. Analyses of the relationship between genotypes and clinical variables indicated that in patients with IgAN, rs1055901 was associated with 24-hour proteinuria, an increase in blood pressure, and Lee's grade (P = 0.04, 0.02, and 0.04, respectively), and rs1055902 was associated with 24-hour proteinuria and Lee's grade (P = 0.03 and 0.01, respectively). However, the results showed no association between these gene variants and sex of the patients.These results indicate that megsin gene variants may play a role in the severity, development, and/or progression of IgAN in Northwest Chinese population.

Lack of Association Between Polymorphisms in AGT and ATR1 and IgA Nephropathy in a Chinese Population.

OBJECTIVE: The mechanism of immunoglobulin A nephropathy (IgAN) remains unclear. Genetic factors may be associated with the risk of IgAN. This study aims to identify the possible association of M268T (rs699) in the Angiotensinogen (AGT) gene and A1166C (rs5186) in the Angiotensin II receptor type 1 (ATR1) gene with IgAN risk. METHODS: Study subjects included 351 patients with IgAN and 310 controls from the Chinese population. The tag SNPs (tSNPs) were genotyped by Sequenom MassARRAY RS1000. Statistical analysis of the association between tSNPs and IgAN was performed using the χ(2) test and SNPStats software. RESULTS: The AGT (M268T) genotypes were distributed in IgAN as CC 61.9%, CT 34.8%, and TT 3.2%, while in controls CC 64.1%, CT 31.3%, and TT 4.6%. Distribution of ATR1 (A1166C) was AA 87.7%, CA 12.3%, and CC 0%, while in controls AA 87.2%, CA 12%, and CC 0.8%. We further analyzed tSNPs under different inheritance models and found that there were no significant differences in the genotypes and allele frequencies of rs699 and rs5186 between two groups (p > 0.05). We also analyzed tSNPs based on the rate of pressure, proteinuria and Lee's classification, and no significant differences were found in the models (p > 0.05). CONCLUSION: rs699 in the AGT gene and rs5186 in the ATR1 gene were not associated with the risk and clinical outcomes of IgAN.

[The impact of ambient particulate matter (PM10) on the population mortality for cerebrovascular diseases-a case-crossover study].

OBJECTIVE: To analyze the association between the concentration of ambient inhalable particulate matter (PM10) and population mortality for cerebrovascular diseases and to explore the impact of PM10 on cerebrovascular diseases. METHODS: Data including meteorological factors, air pollutants (NO2, SO2 and PM10) and cerebrovascular disease mortality in one district of Beijing from 2004 to 2008 were collected and both symmetric bidirectional case-crossover design and conditional logistic regression model were used to analyze the associations among them. RESULTS: After adjusting the influence of meteorological factors as daily average temperature and relative humidity, the single pollutant model showed that there was no significant lag effect. In the multi-pollutant model, the effect of the every 105.43 µg/m(3) increase of ambient PM10 had a larger impact on the daily death of the cerebrovascular diseases with statistically significant difference (P < 0.05). The effect of ambient PM10 pollution on daily death of cerebrovascular diseases was significant for females, 65 year-olds and in winter season. CONCLUSION: Our data showed that elevated levels of ambient PM10 was positively associated with the increase of cerebrovascular disease mortality. The elevated levels of ambient PM10 could lead to the increase of the daily mortality on cerebrovascular diseases for females, elderly who were 65 or older and in winter seasons.

[Association between ambient PM10/PM2.5 levels and population mortality of circulatory diseases: a case-crossover study in Beijing].

OBJECTIVE: To explore the association between levels of ambient particulate matters (PM10 and PM2.5) and population mortality of circulatory diseases (ICD10: I00~I99) in Beijing. METHODS: The daily data of ambient PM2.5 levels were monitored by the research team in Peking University from Jan. 1, 2007 to Dec. 31, 2008, and the corresponding meteorological and other air quality data (PM10, SO2 and NO2) were collected from National Meteorological Information Center (NMIC) of China and Beijing Environmental Monitoring Center. The data of daily death for the circulatory diseases were collected from the local center for Disease Control and Prevention of Haidian District in Beijing. The symmetric bidirectional case-crossover design and conditional logistic regression model were used for the data analysis. The cases were stratified by gender, age and seasons. The lagged effect was analyzed and the related confounders from meteorological factors and other air pollutants were adjusted. RESULTS: For a 10 µg/m(3) increase of the ambient concentration of PM2.5, the corresponding increase of daily mortality of the circulatory diseases, cardiovascular diseases and cerebrovascular diseases was 0.78% (95% CI: 0.07% to 1.49%), 0.85% (95% CI: -0.28% to 1.99%), and 0.75% (95% CI: -0.17% to 1.68%), respectively, for a 10 µg/m(3) increase of the ambient concentration of PM10, the corresponding increase of daily mortality of the circulatory diseases, cardiovascular diseases and cerebrovascular diseases was 0.36% (95% CI: -0.07% to 0.78%), 0.63% (95% CI: -0.02% to 1.28%), and 0.33% (95% CI: -0.26% to 0.92%),respectively. The significant positive associations were observed statistically between PM2.5 and the circulatory diseases (P<0.05). The association between ambient PMs and the population mortality was stronger in "warm season (April to September)" than in "cool season (October to the next March)" in Beijing (P<0.05). CONCLUSION: The elevated levels of ambient PM2.5 and PM10 were positively associated with the increase of the population mortality of the circulatory diseases, and the association is stronger in warm season, and the adverse effect of PM2.5 is greater than that of PM10.

[Relationship between daily mean temperature and emergency department visits for respiratory diseases: a time-series analysis].

OBJECTIVE: To quantitatively evaluate the influences of daily mean air temperature (DMT) on Emergency Department Visits (EDVs) for the respiratory diseases. METHODS: The EDV data from medical records for respiratory diseases in Peking University Third Hospital between January 2004 and June 2009 were collected. The data of the air pollutants (SO(2), NO(2) and PM(10)) and meteorological factors at the same time periods were also collected from the local authorities of Beijing. Time-series analysis and generalized additive models (GAM) were used to explore the exposurrre-response relationship between DMT and EDVs for respiratory diseases. RESULTS: A total of 35 073 patients [males 14 707(41.93%,14 707/35 073), females 19 122(54.52%,19 122/35 073) and gender missing 1 244(3.55%, 1 244/35 073)] EDVs for respiratory diseases were included. The relationship between DMT and EDVs for the respiratory diseases was mainly of "V" shape, the optimum temperature(OT) was about 4 °C and the effect of DMT was significant with a 0-3 day lag structure for most of the models. When DMT≤OT, each 1°C decrease in DMT corresponded to 3.75% (95% CI of RR: 0.938 3-0.965 3), 3.10% (95% CI of RR:0.949 2-0.989 1), 4.09% (95% CI of RR:0.940 7-0.977 8) increase of EDVs for the overall, male, and female, respectively. When DMT>OT, the value caused by each increase in 1°C in DMT was 1.54% (95% CI of RR:1.006 6-1.024 3), 1.80% (95% CI of RR:1.005 3-1.030 9), and 1.51 (95% CI of RR:1.003 2- 1.027 2), respectively. The effect was statistically significant within the 0-3 day lag. When DMT≤OT, the effect was stronger for the older people, while the effect was strongest for the 45-59 years old people. CONCLUSION: The relationship between DMT and EDVs for respiratory diseases is mainly of "V" type, with an optimum temperature of 4 °C.Both DMT decrease when DMT≤OT and increase when DMT>OT correspond to different increase of EDVs for respiratory diseases. Low DMT has stronger effect than high DMT. Different age group and gender have different effects.