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Arsenic is a metalloid environmental carcinogen involved in the occurrence and development of many cancers. miRNA-21 plays a crucial role in arsenic-induced carcinogenesis. We aimed to elucidate the mechanism by which miRNA-21 influences arsenic-induced cancer.We used meta-analysis of published studies to determine how arsenic induces cancerous cells through miRNA-21.Low-dose arsenic exposure (⪕ 5 μmol/L) can increase miRNA-21 and phosphorylated signal transducter and activator of transcription 3 (pSTAT3) expression, and decrease programmed cell death protein 4 (PDCD4) and protein sprouty homolog 1 (Spry1) expression. High-dose arsenic exposure (5 μmol/L), can increase miRNA-21 expression, and decrease Spry1 and E-cadherin expression. Short-term arsenic exposure (⪕ 24 h) can increase miRNA-21 and pSTAT3 expression, and decrease PDCD4 expression. Moreover, long-term arsenic exposure (24 h) can increase the miRNA-21, STAT3, and pSTAT3 expression, and decrease PDCD4 expression. We found that activation of miRNA-21 and pSTAT3 were most pronounced following long-term arsenic exposure at low doses, and the effects on PDCD4 expression were most pronounced following short-term arsenic exposure at low doses. miRNA-21 inhibitors increased the expression of tumor suppressor genes PDCD4, PTEN, and Spry1 and miRNA-21-mimics suppressed the expression of these tumor suppressor genes.Arsenic can cause cancer by activating miRNA-21 and inhibiting the expression of PDCD4, PTEN, and Spry1.

The aim of the present study is to evaluate the ability and mechanism by which grape seed procyanidin extract (GSPE) relieves arsenic trioxide (As2O3)-induced renal inflammatory injury. Therefore, male Kunming mice were treated with As2O3 and/or GSPE by gavage for 5 weeks. Mice were then sacrificed and inflammatory cytokines of kidneys were examined by ELISA, whereas the expression levels of molecules involved in the nuclear factor (NF)-κB signaling pathway were evaluated by both qRT-PCR and Western blot. Our results indicate that GSPE prevents As2O3-mediated renal inflammatory injury by inhibiting activation of the NF-κB signaling pathway and inflammatory cytokine production, while promoting expression of anti-inflammatory cytokines.

The WC–9Ni–2Cr cemented carbides were prepared by ball milling method and low pressure sintering. The microstructure and properties of the cemented carbides were then investigated using scanning electron microscopy, mechanical property tester and immersion corrosion tests. The results showed that the adding method of Cr significantly influenced the microstructure and properties of the WC–9Ni–2Cr cemented carbides. Cemented carbides with Cr added in the form of chromium carbide (Cr 3 C 2 ) were characterized by carburizing and showed a relative lower density, while the addition of metallic chromium and nichrome (Ni–18Cr) resulted in the formation of (W,Cr)C phase and a decrease in the bending strength. However, no defects were found in the microstructure of the cemented carbides in which Cr was added via Cr–Cr 3 C 2 composite powder. Furthermore, cemented carbides prepared with nichrome powder and metallic Cr powder exhibited a higher immersion corrosion resistance in neutral tap water after soaking six times according to BS:6920:2000.

Most previous studies on metabolic syndrome (MetS) examined urban and high income settings. We thus investigated the prevalence of MetS among a multi-ethnic population living in a low income rural area and explored the use of visceral adiposity and anthropometric indicators to identify men and women with MetS. We recruited 10,029 individuals of nomadic Kazakhs, rural Uyghur and Han residents in Xinjiang, China. MetS was defined by the Joint Interim Statement criteria. The receiver operating characteristic curve (ROC) was used to compare the area under the ROC curve (AUC) of each index. The age-adjusted prevalence of MetS was 21.8%. The visceral adiposity index (VAI), lipid accumulation product (LAP), body adiposity index (BAI) and the waist-to-height ratio (WHtR) were significantly associated with MetS, independent of ethnic, age, and other covariates. The AUC of VAI, LAP and WHtR were all greater than 0.7, and the LAP was the index that most accurately identified MetS status in men (AUC = 0.853) and women (AUC = 0.817), with the optimal cut-offs of 34.7 and 27.3, respectively. In conclusion, the prevalence of MetS in low income rural adults of Xinjiang was high and the LAP was an effective indicator for the screening of MetS.

The mechanism of lead (Pb(2+))-induced neurotoxicity has not yet been fully elucidated. The purpose of this study was to examine the effects of Pb(2+) on several protein kinase C (PKC) isoforms and the nuclear factor-kappaB (NF-kappaB)-I-kappaB kinase-alpha (IKK-alpha) axis in cultured neuronal cells. Neurons were isolated from rat fetal brain at the 18th day of gestation of pregnant Sprague Dawley rats and cultured for 10 days before use. Neurons were exposed to Pb(2+) at concentrations of 10(-10), 10(-9), 10(-8), and 10(-7) mol/L for 14 h and antigens of typical PKC-alpha,beta,gamma; novel PKC (epsilon, delta), atypical PKC (lambda), NF-kappaB (p50), and IKK-alpha were enriched by immunoprecipitation and determined by western blotting. Total, calcium-dependent and independent PKC activities were also determined by counting the transferred gamma-(32) P in the substrate-histone. The results indicated that inorganic Pb(2+) significantly reduced all PKC isoforms (alpha,beta,gamma, epsilon, lambda) except delta, inhibiting the total, calcium-dependent and calcium-independent PKC activities in a dose-dependent manner. Additionally, Pb(2+) gradually reduced NF-kappaB (p50) and IKK-alpha protein levels. This suggests that Pb(2+) exhibits varying preference for individual PKC isoforms but reduces the NF-kappaB-IKK-alpha axis to a similar extent.

The objective of this study is to determine the effects of Pb2+ on N-methyl-d-aspartate receptor (NMDAR) subunits--NR1C1, NR2A and NR2B in primary cultured neuronal cells. We hypothesize that L-glutamic acid (GA) reverses Pb2+-induced NMDAR damage. Neuronal cells were isolated from the fetus brain at 18-20th day of gestation of pregnant Sprague Dawley (SD) rats. All experiments were included three independent cell preparations (N=3). The neuronal cells were exposed to Pb2+ (10(-10), 10(-9), 10(-8) and 10(-7)M) for 24 h. Neurons were pretreated with NMDAR agonist--L-glutamic acid (GA) (200 microM) and antagonists dizocipine (MK-801, 50 nM) for 1h and then exposed to 10(-7)M of Pb2+ for 24 h. Finally, GA at 2, 0.2 and 0.02 mM was incubated with neurons prior to Pb2+ exposure. Aliquots of NR1, NR2A and NR2B proteins from cell homogenate were immunoprecipitated with protein A agarose and detected by Western blotting. The addition of GA unconventionally reversed the reductions of NMDAR by Pb at protein levels, whereas MK-801 exacerbated Pb2+-induced damage. The protection by GA against Pb2+-induced reduction of NMDAR was dose-dependent. These findings suggest that the administration of GA may be a potential approach to intervene the Pb2+-induced NMDAR alterations.

To investigate the prevalence and distribution of overweight, obesity and abdominal obesity among rural adult residents in Kazakh, Uygur and Han populations from Xinjiang and to provide the theory gist for prevention and cure on obesity in different ethnic groups.Questionnaire-based survey and physical examination on 11 377 samples were conducted according to stratified cluster random samplings in Kazakh, Uygur and Han residents aged 18 years in Xinjiang. Prevalence rates on overweight, obesity and abdominal obesity between the three ethnic populations were analyzed and compared.The rates of overweight were 27.8%, 24.5% and 40.3% in kazakh, Uygur and Han populations, with the prevalence rates of obesity as 17.9%, 11.5% and 13.7%. However, the rates of abdominal obesity were 58.0%, 53.9% and 59.9%, respectively. The rates of overweight and abdominal obesity were the highest in Han population but the prevalence of obesity was the highest in Kazakh (P0.01). All the prevalence of overweight among the three ethnic populations and the rate of abdominal obesity in Han population were higher in males (P0.05) while the prevalence of obesity in the three ethnic populations and the rate of abdominal obesity in Uygur were diametrically opposite (P0.01). The prevalence rates of overweight, obesity and abdominal obesity all had an increasing trend in the three ethnic populations and the prevalence of abdominal obesity of all age groups was higher than the rates of overweight and obesity in the same age group.The prevalence rates of obesity and abdominal obesity in Kazakh and Uygur populations among rural adult residents were much higher in Xinjiang, so as the rate of overweight in the Hans. All the prevalence rates were different in ethnicities, age groups and sex. The prevalence rate of abdominal obesity was higher than the average data gathered from the nation.

To investigate the prevalence and distribution features of overweight, obesity and abdominal obesity among rural adult residents in Hazakh and Uygur population in Xinjiang province, 2010.Questionnaire-based survey and physical examination were conducted towards the 8611 subjects selected from Hazakh and Uygur residents aged over 18 years old in Yili Xinyuan County and Kashi Jiashi County in Xinjiang province by stratified cluster random sampling method; and thereby the results were analyzed and compared between the two ethnic populations.The prevalence of overweight in Hazakh(male: 29.5% (612/2078) and female: 26.4% (789/2991)) was higher than that in Uygur(male: 25.5% (440/1728) and female: 21.9% (397/1814)). The difference showed statistical significance (male: χ(2) = 7.50, female: χ(2) = 12.27, P0.01). The prevalence was higher in males than in females among the same ethic population (Hazakh: χ(2) = 5.79, Uygur: χ(2) = 6.28, P0.05). The prevalence of obesity in Hazakh(male:18.2% (379/2078) and female:18.1% (540/2991)) was higher than that in Uygur(male: 9.4% (163/1728) and female: 13.2% (240/1814)). The difference showed statistical significance (male: χ(2) = 59.90, female: χ(2) = 19.32, P0.01). The female prevalence was higher than male in Uygur (χ(2) = 12.66, P0.01); however, there was no statistically significant difference in the prevalence stratified by gender in Hazakh. The prevalence of abdominal obesity in Hazakh(male: 57.0% (1185/2078) and female: 60.2% (1801/2991)) was higher than that in Uygur(male: 46.9% (811/1728) and female: 59.5% (1080/1814)). The difference showed statistical significance (male: χ(2) = 38.54, P0.01; female: χ(2) = 0.216, P0.05). And the female prevalence was both higher than male in the two ethic populations (Hazakh: χ(2) = 5.15, P0.05; Uygur: χ(2) = 56.50, P0.01).The prevalence abdominal obesity among rural adult residents in Hazakh and Uygur population was much higher than the average level nationwide in China. Hazakh had a higher prevalence of overweight and obesity than Uygur.

To analyze the prevalence and risk factors of metabolic syndrome (MS) in Xinjiang Uygur adults.With cluster random sampling, investigations including questionnaire, physical examination and blood testing were performed among 3442 Uygur adults among in Kashgar of Xinjiang on November 2010. Prevalence of MS in groups with different characteristics were calculated and non-conditional logistic regression analysis were used to analyze the risk factors.The prevalence of MS was 21.2% (728/3442), and the age-adjusted prevalence was 18.5%. The prevalence among males and females was 14.5% (245/1694) (age-adjusted prevalence 12.7%) and 27.6% (483/1748) (age-adjusted prevalence 24.4%) respectively (P0.05). The prevalence of MS among 18 to 24 years old and 65 years old and above were 4.3% (21/490) and 28.9% (109/377) respectively. The prevalence of MS increased with age (χ(2) = 204.13, P0.05). The prevalence of low blood HDL-C, central obesity, hypertension, hypertriglyceridemia and hyperglycemia was 57.5% (1978/3442), 44.5% (1531/3442), 27.5% (948/3442), 20.2% (696/3442) and 8.6% (297/3442) respectively. Compared to age group 18 - 24, the risk of MS occurrence was higher in age group 25 - 34, 35 - 44, 45 - 54, 55 - 64 and 65 years-old above, the according OR (95%CI) values were 2.29 (1.38 - 3.81), 6.91 (4.31 - 11.09), 10.81 (6.72 - 17.40), 12.52 (7.74 - 20.26) and 10.20 (6.20 - 16.78), respectively. Smoking also increased the risk of MS (OR = 2.35, 95%CI: 1.64 - 3.37).The prevalence of MS in Xinjiang Uygur was in high level; The prevalence of MS is higher in female than in male; The risk factors of MS included female, age and smoking.

To analyze the prevalence of metabolic syndrome (MS) in Kazakh population, using the NCEP-ATPIII, CDS, IDF MS standards.Questionnaire-based survey, physical examination and blood testing were conducted according to cluster random samplings in Kazakh residents in Xinjiang. 2745 samples were collected and diagnosed by NCEP-ATPIII, CDS, IDF standards to analyze the prevalence, with the distribution of its main components of MS, among the Kazakhs population.The prevalence rates of MS diagnosed by NCEP-ATPIII, CDS, IDF standards were 18.5%, 14.2% and 26.6%, while they became 14.2%, 10.9% and 20.1% after standardized by age. The prevalence of MS diagnosed by NCEP-ATPIII and IDF standard in males were higher than in females, while CDS was in the opposite situation. The prevalence of MS by these three standards increased with age. Among all the main components of MS diagnosed after these three standardization process, the prevalence of obesity, blood pressure rising and the abnormity of HDL-C were rather high. The prevalence of MS main components ≥ 1, ≥ 2, ≥ 3, ≥ 4, 5 ranked the highest compared to the lowest as to the IDF, ATPIII' and CDS diagnostic. standardsThe prevalence rates and gender distribution of MS diagnosed by different standards among Kazakhs were different. The prevalence of IDF standard was the highest, with the IDF standard better than the others in early identifying the risk factors of cardiovascular disease.

To investigate the polymorphism of angiotensin II type 1 receptor (AT(1R)) gene A1166C and environmental factors on hypertension of Kazakh people.Through the random program of SPSS 13.0, 220 cases were randomly selected from the confirmed hypertension patients, and 220 cases with normal blood pressure were selected as control group. All cases were investigated through the questionnaire and the related indexes were measured. By polymerase chain reaction (PCR) method, the genotypes were determined.(1) In hypertension group, the genotype frequency of AA and AC were 78.6% (173/220) and 21.4% (47/220), respectively, compared with control groups' 81.4% (179/220) and 18.6% (41/220), no significant difference was identified between these two groups (chi(2) = 0.537, P0.05). In hypertension group, the frequency of A and C allele were 89.0% and 11.0%, respectively, compared with 90.3% and 9.7% in control group. There was no significant difference between these two groups (chi(2) = 0.37, P0.05). (2) AC genotype might interact with excessive salt consumption (hypertension group, 31/220, 15.5%; control group 10/220, 4.5%, OR: 4.67, 95%CI: 2.15 - 10.15), overweight (hypertension group, 19/220, 8.6%; control group, 9/220, 4.1%, OR: 6.96, 95%CI: 2.33 - 20.76) and drinking large volume of salty milk (hypertension group, 20/220, 9.1%; control group, 10/220, 4.5%, OR: 2.67, 95%CI: 1.11 - 6.42) which will raise hypertension hazard of AC genotype.There is no relationship between the A1166C gene polymorphism of AT(1R) gene and hypertension of Kazakh people. AC genotypes might also interact with food consumption habit and behavior factors and increase the individual risk of hypertension.

The homeobox transcription factor Prox1 plays an important role in the development of many embryonic organs. Previous studies indicated that Prox1 facilitates hepatic progenitor-cells proliferation. However, the underlying mechanism of Prox1 in tumor genesis, formation, and progression are poorly understood and need to be exploited. Herein, Chinese Hamster Ovary (CHO) cells were transfected and over-expressed human recombinant Prox1 gene, and developed several stable cell lines of Prox1-CHO after screening. The results indicated that over expression of Prox1 increased CHO cell proliferation in comparison to GFP-CHO and parental CHO cells, and Prox1 increased AKT phosphorylation and up-regulated PI3 Kinase expression. An AKT specific inhibitor-AKTi—X (5 μM) and a PI3 K inhibitor—LY294002 (5 μM) were able to reverse AKT phosphorylation and PI3 K expression induced by Prox1, respectively. Furthermore, AKTi-X but LY-294002 decreased Prox1-CHO cell proliferations at 48 and 72 h. Our results suggest that over expression of Prox1 facilitates CHO cell proliferation via activation of the AKT signaling pathway. This finding provides new insights into the mechanism of Prox1 mediated tumor growth and metastasis where Prox1 is rich.

To describe the prevalence of anemia and yearly trends (1993-2003) among women who came to the hospitals or maternal and child health units for premarital examinations in 6 counties of Jiangsu and Zhejiang provinces.Data were obtained from the records of the premarital examinations in perinatal health care surveillance system that had been established since 1992 in these areas. We reviewed hemoglobin levels of those women who were enrolled in the perinatal health care surveillance system from 1993 to 2003. Anemia was defined according to the WHO (2001) criterion. We calculated the prevalence of anemia and analyzed the yearly trends based on the data of hemoglobin concentration.In the period of 1993-2003, there were 82 995 anemia cases identified among 193,434 women with an overall anemia rate as 42.9%. The rates of anemia were high (65.5%) in 1993 but low (25.8%) in 2003. 99.7% of the anemic women whose hemoglobin concentration were between 80-119.9 g/L. Time trend analysis indicated a significant decline on anemia rate while monthly analysis showed that the prevalence rates were high (48.2%) in September and low in March (39.5%). The results also showed that the prevalence rates of anemia were relatively higher in farmers and workers in rural enterprises, and lower in Han ethnicity than minorities. The higher prevalence rates of anemia were presented among the women with less education, lower body mass index, or at older age.For those premarital women in 6 counties of Jiangsu and Zhejiang provinces, the overall anemic rate presented a significant downward trend between 1993 and 2003 while the prevalence of anemia remained high, especially for the women with less education, lower body mass index or older ages.

Rottlerin has been widely accepted as a specific inhibitor of protein kinase C delta (PKC delta); however, recent data suggest that the specificity of this compound become a question. Herein, we address this issue using a lens organ culture system, as PKC delta might regulate the gap junction permeability in lens. Interestingly, we found that rottlerin induced the degradation of connexin50 more rapidly than that of PKC delta. Furthermore, comparison of rottlerin with a protonophore, carbonylcyanide-4-(trifluoromethoxy)-phenylhydrazone (FCCP) that shares many characteristics with rottlerin, showed that both rottlerin and FCCP dramatically increased lens weight over time. This increase in lens weight was partially reversed by depletion of extracellular calcium with ethyleneglycoltetraacetic acid (EGTA) or by blocking L-type calcium channels with verapamil, suggesting rottlerin may induce calcium influx. Indeed, the rapid degradation of connexin50 (but not PKC delta) induced by rottlerin and FCCP was blocked by EGTA. In addition, rottlerin and FCCP also induced degradation of connexin46, filensin, vimentin and CP49. In order to determine whether this protein degradation is associated with the decrease of ATP due to uncoupling mitochondria by rottlerin, ATP content in lenses with different treatments were examined. The result indicated that EGTA had no effect on lens ATP content. Taken together, these data suggest that rottlerin, like FCCP, induces calcium influx, leading to protein degradation and cleavage in the lens, and that this effect is unrelated to the inhibition of PKC delta. Thus, extreme caution must be taken when considering use of rottlerin as a PKC delta inhibitor.

A plethora of protein kinase C (PKC) isoforms play important roles in regulating synaptic plasticity and neurotransmitter release. Even though, most PKC isoforms are involved in Pb-induced neuronal toxicity, its mechanism is still unclear. The current study addresses the effect of Pb on PKC isoforms in different regions of the developing rat brain. Sprague-Dawley (SD) pregnant rats were exposed to 0.1% Pb as lead acetate dissolved in distilled deionized water (DDW) from gestation day 6 through 21 postnatal day (PND). Control rats were allowed to drink DDW. Pups were sacrificed on PND 1, 5, 10 and 45. Rat brain was immediately excised and separated into the brain stem (BS), the cerebellum (CB), the hippocampus (HC) and the frontal cortex (FC). The Pb level in different regions of the brain was determined using an analytical graphite tube atomizer (Varian). Typical PKC (alpha, beta, gamma), novel PKC (epsilon) and atypical PKC (mu) in the above brain regions were enriched by immunoprecipitation and later were assayed by Western blotting. The total, calcium-dependent and -independent PKC activities were determined by the radioactivity of total gamma-32P transferred to histone. The results indicated that on PND 1, Pb reduced the PKC-gamma protein in HC and FC, whereas on PND 5 the proteins of PKC isoforms (alpha, beta, gamma, epsilon, mu) in HC and FC were significantly reduced. These reductions in PKC proteins were higher in membrane fractions than in cytosolic fractions. On PND 10, Pb reduced all PKC isoforms. However, on PND 45, Pb had no significant effect on all PKC isoforms except epsilon. Pb inhibited the total PKC activity by 70% on PND 1 and 5, the bulk of these PKC activities were calcium-dependent. The results suggest that during early stages of the rat brain development, Pb exposure decreased PKC activities and also reduced PKC isoforms including PKC-gamma and epsilon which are reported to have roles in the memory formation and long-term potentiation (LTP).

It has much more advantages to preserve human red blood cells (RBC) in freezing and drying form than conventional blood storage, even though it is still under developing. In the present study, we successfully used 0.045% glutaraldehyde(GA) to fix RBCs under appropriate conditions prior to lyophilization and regained the bulk of RBCs membrane filterability. The phlebotomized whole blood was anti-coagulated with CPDA-1 and the plasma was removed by centrifugation. White blood cells were removed using Leucocytes filter (Pall Corporation). 1 x 10 9 cells/ml were separately incubated with 0.03%, 0.045% and 0.05% GA at 37 °C for 10 min; RBCs at concentrations 0.5 x 10 9, 1 x 10 9 and 2 x 10 9 cell/ml were incubated with 0.045% GA at 37 °C for 10 min; Bovine serum albumin (BSA), trehalose, hydroxyethyl starch and dextran were used as protective additive in freezing and drying RBCs, respectively; ethanolamine, glycine, lysine, BSA, glutamic acid and homocysteic acid were used to recover membrane deformability due to GA fixation. Recovery RBCs yield after reconstituion was determined by a cell counter. Fee hemoglobin , glutathione (GSH), 2,3-diphosphoglycerate (2,3-DPG), ATP, and Glucose-6-phosphate dehydrogenase (G-6-PDH) in RBCs were determined before and after lyophilization. Membrane flexibility was assayed by osmotic fragility test. RBCs filterability was determined using positive filter apparatus through 5 micrometer pore size nitrocellulose membrane. Our results suggested that RBCs at 1 x 10 9 cells/ml fixed by 0.045% GA for10 min at pH 7.8 were enough to resist freezing and drying damages and the bulk of RBCs’s membrane filterability were remained. The effective fixation of GA is dependent on GA’s concentration, RBCs concentration, incubation period and pH etc. BSA is the most potential additive in preserving RBCs. More interestingly, the following reagents can recover the reduced RBCs membrane filterability by GA fixation. The potency of recovery is in the order of : 10 mM ethanolamine > 5 mM lysine > 0.5%BSA > 10 mM glutamatic acid > 5 mM homcysteic acid > 2% glycine. After reconstitution, 85 ± 2.3% RBCs yield is achieved, 71 ± 4.1% of these RBCs can freely pass through 5 micrometer pore size filter membrane. Biochemical function indexes as GSH, 2,3-DPG, ATP, and G-6-PDH are saved by 20 ± 1.2%. Lyophilized human red blood cells yields from reconstitution by different treatment. 1x 109 cells/ml fixed at 0.03% glutaraldehyde 44.7 ± 4.1 0.045%glutaraldehyde 84.7 ± 5.8 0.05%glutaraldehyde 88.7 ± 7.6 0.045% glutaraldehyde fix: 0.5x 109 cells/ml 91 ± 4.3 1x 109 cells/ml 84.7 ± 5.8 2 x 109 cells/ml 35.2 ± 2.3 Effects of various treatment on lyophilized RBCs after reconstitution. Group Filterability(%) 1x9 cells/ml fixed by: N = 5. 0.03%glutaraldehyde 88.3 ± 1.2 0.045%glutaraldehyde 73.3 ± 1.8 0.05%glutaraldehyde 44.7 ± 2.8 0.045%glutaraldehyde fixation at: 0.5x109 cells/ml 0 1x109 cells/ml 73.3 ± 1.8 2x109 cells/ml 83.9 ± 4.6