Nano-Microemulsions of CaCO3-Encapsulated Curcumin Ester Derivatives With High Antioxidant and Antimicrobial Activities and pH Sensitivity.

In this study, we synthesized nano-microemulsions of calcium carbonate (CaCO3)-encapsulated curcumin (Cur)-Ferulic acid (FA) ester derivatives of diverse mass ratios by using the solution casting approach. The structures, antioxidant and antimicrobial activities, physical properties, and potential of hydrogen (pH) sensitivity of these products were examined. Compared with microparticles of CaCO3, those of CaCO3@Cur-FA exhibited excellent antimicrobial and antioxidant properties. Response to pH was indicated through the release of Cur-FA from CaCO3@Cur-FA in solutions having different pH values. The results demonstrated that Cur-FA was released more quickly from CaCO3@Cur-FA at pH 5.5 than at pH 7.4. CaCO3@Cur-FA demonstrated good antioxidant capacities through its ability to scavenge 2,2'-amino-di(2-ethyl-benzothiazoline sulphonic acid-6)ammonium salt (ABTS+) and 1,1-diphenyl-2-picrylhydrazyl (DPPH). These activities were three-fold more than those observed in CaCO3 microparticle control groups; additionally, the antimicrobial activity against Aspergillus niger and Escherichia coli increased by 40.5 and 54.6%, respectively. Overall, the microparticles of CaCO3@Cur-FA outperformed Cur-FA in terms of antimicrobial properties by inhibiting the growth of certain zoonotic pathogens.

Transcriptome analysis to reveal the mechanism of the effect of Echinops latifolius polysaccharide B on palmitate-induced insulin-resistant.

Hepatic insulin resistance is a crucial pathological process in type 2 diabetes mellitus (T2DM) associated with visceral adiposity and metabolic disorders. Echinops latifolius polysaccharide B (ETPB), a polysaccharide extracted from Echinops latifolius Tausch, increases insulin sensitivity in the high-fat diet-fed and STZ induced SD rat model and even prevented hepatic metabolic disorders. However, the mechanism by which ETPB improves carbohydrate and lipid metabolisms in the liver with insulin resistance remains largely unknown. In the present work, an lnsulin resistance cell model (IR-HepG2) was established. Glucose consumption, glycogen content, triglycerides (TG), and free fatty acids (FFAs) levels were detected. The result revealed that the intervention of ETPB significantly increased glucose consumption and glycogen synthesis and reduced FFAs and TG production in IR-HepG2 cells. Further, we also employed RNA-seq to identify differentially expressed miRNAs (DEMs) and mRNAs (DEGs) with a fold change of ≥ 1.5 and p-value of <0.05. Finally, we identified 1028, 682, 382, 1614, 519 and 825 DEGs, and 71, 113, 94, 68, 52 and 38 DEMs in different comparisons, respectively. Based on a short time-series expression miner (STEM) analysis, six profiles were chosen for further analysis. Seventeen insulin resistance-associated dynamic DEGs were identified during ETPB stimulation. Based on these dynamic DEGs, the related miRNAs were acquired from DEMs, and an integrated miRNA-mRNA regulatory network was subsequently constructed. Besides, some DEGs and DEMs were validated using qPCR. This study provides transcriptomic evidence of the molecular mechanism involved in HepG2 insulin resistance, leading to the discovery of miRNA-based target therapies for ETPB.

miR-375 Promotes Pancreatic Differentiation In Vitro by Affecting Different Target Genes at Different Stages.

Human embryonic stem cells (hESCs) possess the ability to differentiate into insulin-producing cells (IPCs), which can be used to treat type I diabetes. miR-375 is an essential transcriptional regulator in the development and maturation of the pancreas. In this study, we optimized a protocol to differentiate hESCs into IPCs and successfully obtained IPCs. Then, we performed overexpression and inhibition experiments of miR-375 on cells at different stages of differentiation and performed RNA-seq. The results showed that the expression of miR-375 fluctuated during hESC differentiation and was affected by miR-375 mimics and inhibitors. miR-375 influences global gene expression and the target genes of miR-375. The overexpression of miR-375 can cause changes in multiple signaling pathways during pancreatic development. miR-375 is a major participant in the differentiation of pancreatic ß-cells through different target genes at different stages. This study provides new ideas for further investigation of how microRNAs affect cell fate and gene transcription.

Changes in urinary arsenic species and methylation capacity in original arsenic exposure cohort after water quality improvement.

Water quality improvement is the most efficient way to prevent arsenic exposure. After the cessation of arsenic ingestion, arsenic methylation capacity of the exposed population can change significantly. The factors associated with these changes remain poorly understood. Therefore, arsenic methylation capacity in a study cohort was estimated before and after water quality improvement in the present study. Results indicated that urinary content of the arsenic species in the study cohort significantly decreased after water quality improvement. In addition, the proportions of inorganic arsenic (%iAs) and monomethyl arsenic acid (%MMA) were significantly decreased, while proportions of dimethyl arsenic (%DMA) increased. The primary methylation index (PMI) and secondary methylation index (SMI) increased from 0.85 to 0.92 and 0.82 to 0.84, respectively. Arsenic species urinary content and arsenic methylation index varied slightly between the study cohort after water quality improvement and the control cohort. The rate of increase in PMI was higher than that in SMI. The study group aged 31-50 years had the highest increase in PMI. Logistic regression revealed that %DMA before water quality improvement was negatively associated with the increase in PMI, while %iAs were positively related, and %MMA were positively associated with the increase in SMI. It is concluded that urinary arsenic species content and arsenic methylation capacity increased to the levels of the control cohort after water quality improvement. An increase in primary arsenic methylation capacity may be a burden on the secondary arsenic methylation capacity. The main role of arsenic methylation capacity recovery may be the cessation of arsenic exposure.

A follow-up study of the development of skin lesions associated with arsenic exposure duration.

Little information about the development of skin lesions in relation to arsenic exposure duration is available. Therefore, skin lesions in a cohort from the Bameng region of China were diagnosed in 2012 and 2017. The results indicated that the prevalence of hyperkeratosis, pigmentation and depigmentation in 2017 was 64.67, 6.67 and 12.67%. There were 42 and 34% of male subjects and female subjects suffered from skin lesions in 2012. Their morbidity rates were 10.43 and 8.98 per 1000 person-years. In 2017, the values were significantly increased. The prevalence and morbidity rate of skin lesions were positively correlated with age and arsenic levels in drinking water. Males had higher prevalence of skin lesions compared with female. However, the ≤ 40 years female group had higher prevalence of skin lesions. In addition, the increased rate of skin lesions prevalence was negatively correlated with arsenic levels in drinking water. The odds ratios (ORs) showed that the risks of skin lesions were positively associated with the proportion of inorganic arsenic (%iAs) and monomethylarsonic acid (%MMA) in urine, and negatively correlated with arsenic methylation capacity in both 2012 and 2017. It can be concluded that females immigrated from other areas were more susceptible to developing skin lesions. A certain cumulative arsenic exposure dose, which may be existing, significantly increased the prevalence of skin lesions. Longer arsenic exposure duration might elevate the toxicity of iAs to skin lesions and reduce the positive effects of arsenic methylation capacity on skin lesions.

Effects of arsenic methylation and metabolism on the changes of arsenic-related skin lesions.

Little was known about the arsenic metabolism and arsenic methylation associated with the changes of skin lesions after reducing the arsenic in drinking water (WAs). Therefore, urinary concentrations and proportions of arsenic species were determined for recovery (RC), improvement (IC), persistent (PE), aggravation (AC), new incidence (NC), and no sign (HC) groups based on the changes of skin lesions between before (in 2004) and after (in 2017) WAs reduction. The results indicate that the urinary concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and total arsenic (TAs) were much higher for RC and IC groups than for the other groups in 2004, while these values varied slightly among the groups in 2017. The urinary %iAs of all the groups was significantly decreased after WAs reduction. In contrast, the urinary %DMA of RC, IC, AC, and NC groups was increased. From 2004 to 2017, the PE and HC groups had lower decrease rate of %iAs and %MMA, and increase rate of %DMA, primary methylation index (PMI), and secondary methylation index (SMI) after WAs reduction. The adjusted odd ratios (ORs) showed that the RC, IC, AC, and NC groups were positively related with %iAs and %MMA and were negatively correlated with %DMA, PMI, and SMI before WAs reduction. It can be concluded that higher urinary %iAs and %MMA before WAs reduction increased the probability of skin lesions recovery and improvement, and the risks of skin lesions aggravation and incidence. Higher increase rate of urinary %DMA was positively associated with of skin lesions recovery and improvement. Moreover, higher urinary %iAs and %MMA or lower increase rate of urinary %DMA might increase the risk of skin lesions aggravation.

An investigation of the health effects caused by exposure to arsenic from drinking water and coal combustion: arsenic exposure and metabolism.

Few studies have been conducted to compare arsenic exposure, metabolism, and methylation in populations exposed to arsenic in drinking water and from coal combustion. Therefore, arsenic concentrations in the environment and arsenic speciation in the urine of subjects exposed to arsenic as a consequence of coal combustion in a rural area in Shaanxi province (CCA) and in drinking water in a rural area in Inner Mongolia (DWA) were investigated. The mean arsenic concentrations in drinking water, indoor air, and soil in CCA were 4.52 µg/L, 0.03 mg/m3, and 14.93 mg/kg, respectively. The mean arsenic concentrations in drinking water and soil in DWA were 144.71 µg/L and 10.19 mg/kg, respectively, while the level in indoor air was lower than the limit of detection. The total daily intakes of arsenic in DWA and CCA were 4.47 and 3.13 µg/day·kg, respectively. The mean urinary concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsenic acid (DMA), and total arsenic (TAs) for subjects with skin lesions in DWA were 50.41, 47.01, 202.66, and 300.08 µg/L. The concentrations for subjects without skin lesions were 49.76, 44.20, 195.60, and 289.56 µg/L, respectively. The %iAs, %MMA, and %DMA in the TAs in the urine of subjects from CCA were 12.24, 14.73, and 73.03%, while the corresponding values from DWA were 17.54, 15.57, and 66.89%, respectively. The subjects in DWA typically had a higher %iAs and %MMA, and a lower %DMA, and primary and secondary methylation index (PMI and SMI) than the subjects in CCA. It was concluded that the arsenic methylation efficiency of subjects in DWA and CCA was significantly influenced by chronic exposure to high levels of arsenic in the environment. The lower PMI and SMI values in DWA revealed lower arsenic methylation capacity due to ingestion of arsenic in drinking water. However, it remained unclear if the differences in arsenic metabolism between the two groups were due to differences in exposure levels or in exposure route.

The relationships between arsenic methylation and both skin lesions and hypertension caused by chronic exposure to arsenic in drinking water.

The associations between arsenic exposure, arsenic methylation, and the prevalence of skin lesions and hypertension are investigated. The results indicate that the HS (hypertension and skin lesions) group and the S (skin lesions) group have higher urinary concentrations of iAs (inorganic arsenic), MMA (monomethylarsonic acid), DMA (dimethylarsinous acid) and%MMA, and lower SMI (secondary arsenic methylation index) compared to the H (hypertension) and N (without both hypertension and skin lesions) groups. The arsenic content in water which caused H may be lower than that which caused HS and S. In addition, the odds ratios suggest that higher urinary concentrations of iAs and MMA, %iAs, %MMA and PMI elevate the prevalence of only hypertension and skin lesions, and both hypertension and skin lesions. However, higher%DMA and SMI, and lower%MMA increase the prevalence of both hypertension and skin lesions compared to that of only skin lesions. It can be concluded that skin lesions subjects have higher prevalence of hypertension. Hypertension subjects may have higher prevalence of skin lesions. Lower%DMA and SMI, higher%iAs, %MMA and PMI enhance the prevalence of only hypertension and skin lesions, and both hypertension and skin lesions. Moreover, iAs and MMA may have higher toxicity and lead to both hypertension and skin lesions than to only hypertension.

Associations of arsenic metabolites, methylation capacity, and skin lesions caused by chronic exposure to high arsenic in tube well water.

To investigate the interaction between skin lesion status and arsenic methylation profiles, the concentrations and proportions of arsenic metabolites in urine and arsenic methylation capacities of study subjects were determined. The results showed that the mean urinary concentrations of iAs (inorganic arsenic), MMA (monomethylarsonic acid), DMA (dimethylarsinic acid), and TAs (total arsenic) were 75.65, 68.78, 265.81, and 410.24 µg/L, respectively, in the skin lesions subjects. The highest values were observed in the multiple skin lesions subjects. Higher %iAs and %MMA, and lower %DMA, PMI (primary methylation index), and SMI (secondary methylation index) were found in skin lesions subjects. The multiple skin lesions subjects had highest %iAs and %MMA, and lowest %DMA, PMI, and SMI. The prevalence of skin lesions strongly, positively correlated with arsenic levels in drinking water. The elder persons also had higher frequency of skin lesions compared with younger persons. It can be concluded that arsenic levels in drinking water significantly affected the prevalence of skin lesions. Male subjects usually had higher proportions of skin lesions when compared with female subjects. Moreover, it may be concluded that MMA was significantly related to single skin lesion, whereas DMA and iAs were associated with multiple skin lesions. It seemed that MMA had greater toxicity to hyperkeratosis, whereas DMA and iAs had higher toxicity to depigmentation or pigmentation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 28-36, 2017.

Arsenic methylation and skin lesions in migrant and native adult women with chronic exposure to arsenic from drinking groundwater.

In order to figure out the prevalence of skin lesions and methylation capacity for migrant and native adult women in an endemic area for arsenic poisoning in Inner Mongolia, China, 207 adult women were selected for study subjects. The results showed that the prevalence of skin lesions for the external group, provincial group and native group was 36.54, 26.15 and 35.56 %, respectively. The nail content of arsenic and urinary concentrations of dimethylarsenic (DMA), monomethylarsenic (MMA) and inorganic arsenic (iAs) were significantly higher in women with skin lesions than in those without skin lesions. The highest urinary concentrations of DMA, MMA and iAs were 213.93, 45.72 and 45.01 µg/L in the native group. The arsenic methylation capacity index revealed that the external group had the greatest capacity, while the native group had the lowest. The odds ratios of skin lesions in relation to arsenic metabolites and arsenic methylation capacity varied widely among the three groups. Urinary MMA and iAs concentrations were positively associated with risk of skin lesions in the three groups of adult women, while primary and secondary methylation capacities were negatively related to risk of skin lesions in native and provincial groups. The external group might be more susceptible to MMA and iAs, while the provincial and native groups were more tolerance to MMA and iAs. Lower primary and secondary arsenic methylation capacities increased the risk of skin lesions in native and provincial groups. Moreover, higher nail arsenic concentration increased the risk of skin lesions of adult women.

[Effects on serum hormones of rats exposed to subchronic low-dose arsenic].

OBJECTIVE: To study the effect on endocrine system of SD rats exposed to low-dose arsenic. METHODS: A subchronic test on rats which were divided into five groups randomly( the control group, 0. 05, 0. 1, 0. 2, 0. 4 µg / m L), 20 rats each group, half male and female. A total of 200 rats were allowed to acclimate for 1 week and their hormones level were measured by RIA method after 110 and 194 days. RESULTS: The hormones level of rats was disordered in different groups. The T level of male rats exposedto arsenic for 110 days were( 4. 80 ± 4. 26), ( 4. 54 ± 3. 31), ( 1. 27 ± 1. 51), ( 1. 93 ±2. 23) and( 4. 83 ± 2. 31) ng / m L( P = 0. 05), respectively. The T4 level of each female group were( 40. 20 ± 7. 10), ( 40. 85 ± 8. 66), ( 46. 49 ± 8. 52), ( 44. 66 ± 11. 83) and( 26. 80 ± 8. 12) ng /m L, compared with control group, 0. 4 µg /m L group decreased obviously( P < 0. 05). Meanwhile, their Cort level of each group were( 312. 10 ±10. 61), ( 333. 15 ± 15. 73), ( 341. 13 ± 19. 25), ( 342. 59 ± 25. 96) and( 314. 84 ±16. 76) ng / m L, and the 0. 05, 0. 1 and 0. 2 µg / m L groups were significantly increased( P < 0. 05). Furthermore, the T4 level of male groups exposed to arsenic for 194 days were( 23. 06 ± 5. 54), ( 33. 18 ± 5. 29), ( 34. 23 ± 4. 15), ( 37. 19 ± 4. 13) and( 39. 92± 6. 27) ng / m L, respectively. Compared with control group, all experimental group significantly increased( all P < 0. 05). Additionally, the T3 level of female group were( 0. 84 ± 0. 12), ( 0. 89 ± 0. 14), ( 0. 83 ± 0. 15), ( 0. 96 ± 0. 16) and( 0. 75 ± 0. 11)ng / m L, and 0. 2 µg / m L group obviously increased( P < 0. 05). Obvious change of hormone had not been found in other group exposed to subchronic low-dose arsenic( all P> 0. 05). CONCLUSION: Subchronic low-dose arsenic exposure have slight endocrine effects on SD rats.

Arsenic Metabolites and Methylation Capacity Among Individuals Living in a Rural Area with Endemic Arseniasis in Inner Mongolia, China.

More than 0.3 million individuals are subject to chronic exposure to arsenic via their drinking water in Inner Mongolia, China. To determine arsenic methylation capacity profiles for such individuals, concentrations of urinary arsenic metabolites were measured for 548 subjects using high-performance liquid chromatography and a hydride generator combined with inductively coupled plasma-mass spectrometry. Mean urinary concentrations of dimethylarsonic acid (DMA), monomethylarsonic acid (MMA), inorganic arsenic (iAs), and total arsenic (TAs) were 200.50, 46.71, 52.96, and 300.17 µg/L, respectively. The %iAs, %DMA, and %MMA were 15.98, 69.72, and 14.29%. Mean urinary %iAs and %MMA were higher in males, while urinary %DMA was higher in females. There was a strong positive correlation between %iAs and %MMA, with negative correlations between %iAs and %DMA, and %iAs and %MMA. In addition, %iAs and %MMA were positively associated with total arsenic in drinking water (WAs), while %DMA was negatively related with WAs. Regression analysis indicated that the primary methylation index (PMI) and secondary methylation index (SMI) generally decreased with increasing WAs. Females had a higher arsenic methylation capacity compared to males. Younger subjects had lower primary arsenic methylation capacity. However, the secondary arsenic methylation capacity was hardly affected by age. Moreover, both primary and secondary arsenic methylation capacities were negatively related to WAs.

Cardiovascular disease and arsenic exposure in Inner Mongolia, China: a case control study.

BACKGROUND: Millions of people are at risk from the adverse effects of arsenic exposure through drinking water. Increasingly, non-cancer effects such as cardiovascular disease have been associated with drinking water arsenic exposures. However, most studies have been conducted in highly exposed populations and lacked individual measurements. OBJECTIVE: To evaluate the association between cardiovascular disease and well-water arsenic exposure. METHODS: We conducted a hospital based case control study in Inner Mongolia, China. Cases and controls were prospectively identified and enrolled from a large hospital in the Hangjin Hou area. Cases were patients diagnosed with cardiovascular disease and controls were patients free from cardiovascular disease, admitted for conditions unrelated to arsenic exposure. Water from the primary water source and toenail samples were collected from each subject and tested for inorganic arsenic. RESULTS: Arsenic exposures were moderate with mean and median arsenic exposures of 8.9 µg/L and 13.1 µg/L, respectively. A total of 298 cases and 275 controls were enrolled. The adjusted odds ratio (AOR) and corresponding 95% confidence interval (95% CI) for a 10 µg/L increase in water arsenic were 1.19 (95% CI: 1.03, 1.38). Compared to exposures less than 10 µg/L, the AOR for water arsenic exposures above 40 µg/L was 4.05 (95% CI: 1.1-14.99, p = 0.04). Nail arsenic above 1.38 µg/g was also associated with an increased risk of cardiovascular disease. CONCLUSIONS: By using standardized case definitions and collecting individual measurements of arsenic, this study addressed several limitations of previous studies. The results provide further evidence of the association between cardiovascular disease and arsenic at moderate exposures.

[Expression and significance of ERalpha mRNA of residents exposed to arsenic via drinking water].

OBJECTIVE: To detect ERbeta mRNA expression of subjects exposed to different arsenic drinking water, and to analyze the potential relationship between their abnormal expression and heart injury caused by arsenic in order to study the endocrine disturbing effect of arsenic. METHODS: Molecular epidemiological method was used. The study subjects included a total of 273 residents exposed to arsenic via drinking water,and they were divided into four groups according to arsenic concentration, and their blood ERbeta mRNA expression was detected by real-time RT-PCR. RESULTS: The level of ERbeta mRNA expression rose with increasing of water As and urine As (r = 0.159, 0.21, P < 0.05). The prevalence of Q-Tc interval prolongation aggravated with increasing of water As(chi2 = 4.35, P = 0.037), while according with the variation of ERbeta mRNA expression. Tp-Te interval prolonged with increasing of water As (r = 0.199, P = 0.023), as well prolonged with increasing of ERbeta mRNA expression (r = 0.205, P = 0.019). The prevalence of arrhythmia was almost according with the variation of ERbeta mRNA expression. CONCLUSION: chronic arsenic exposure can potentially disturb ERbeta mRNA expression, as well as there are possible relationship between ERbeta mRNA abnormal expression and Q-Tc interval prolongation and Tp-Te interval prolonged caused by arsenic.

Altered gene expression by low-dose arsenic exposure in humans and cultured cardiomyocytes: assessment by real-time PCR arrays.

Chronic arsenic exposure results in higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. The purpose of this study was to investigate the effects on expression of selected genes in the blood lymphocytes from 159 people exposed chronically to arsenic in their drinking water using a novel RT-PCR TaqMan low-density array (TLDA). We found that expression of tumor necrosis factor-α (TNF-α), which activates both inflammation and NF-κB-dependent survival pathways, was strongly associated with water and urinary arsenic levels. Expression of KCNA5, which encodes a potassium ion channel protein, was positively associated with water and toe nail arsenic levels. Expression of 2 and 11 genes were positively associated with nail and urinary arsenic, respectively. Because arsenic exposure has been reported to be associated with long QT intervals and vascular disease in humans, we also used this TLDA for analysis of gene expression in human cardiomyocytes exposed to arsenic in vitro. Expression of the ion-channel genes CACNA1, KCNH2, KCNQ1 and KCNE1 were down-regulated by 1-µM arsenic. Alteration of some common pathways, including those involved in oxidative stress, inflammatory signaling, and ion-channel function, may underlay the seemingly disparate array of arsenic-associated diseases, such as cancer, cardiovascular disease, and diabetes.

[Effects on endocrine system of female rats exposed to chronic arsenic].

OBJECTIVE: To study the effect on endocrine system of female rats exposed to chronic arsenic. METHODS: 50 female Wistar rats were randomly divided into five groups: control group, 0.05, 0.1, 0.2 and 0.4 microg/ml arsenic groups. The hormone levels were determined by RIA exposing arsenic for 32 weeks. RESULTS: The hormone levels of female rats were disorder in different arsenic groups. E2, P level increased and LH level decreased in arsenic groups compared to controls, but there were no significant differences( P > 0.05). FSH and PRL level increased in low arsenic group and decreased in high arsenic groups (P > 0.05). GnRH and Cort level increased in arsenic groups, and GnRH level obviously increased in 0.4 microg/ml group and Cort level obviously increased in 0.1 and 0.4 microg/ml groups (P < 0.05). CONCLUSIONS: The hormone levels were disordered in rats exposed to chronic arsenic.

[Effects on serum estadiol and progesterone of female mice exposed to arsenic chronically].

OBJECTIVE: By measure the changes of serumal estadiol and progesterone levels of kunming female mice, which are chronically exposed to different concentrations of arsenic trioxide, discuss the estrogen-like effects of arsenic. METHODS: Select the Kunming female mice exposed to different drinking water of arsenic trioxide (0, 0.05, 0.10, 0.20, 0.40 microg/ml) for 20 weeks as the research subjects in this study. Use the method of radioimmunology to measure concentrations of serumal estadiol and progesterone of female adult mice. RESULTS: Compared with the control group, there exists the changes of the concentrations of the serumal estadiol and progesterone of Km female adult mice, which are chronically exposed to the arsenic. Compared to the control group, the differences of the concentrations of the serumal estadiol in the 0.05 microg/ml group and 0.10 microg/ml group have no statistical significance (P > 0.05), the concentrations of estadiol in the 0.20 microg/ml group (P < 0.01) and 0.40 microg/ ml group (P < 0.05) decrease. Compared to the control group, the differences of the concentrations of the serumal progesterone in the 0.05 microg/ml group, 0.20 microg/ml group and 0.40 microg/ml group have no statistical significance (P > 0.05), the concentration of serumal progesterone in the 0.10 microg/ml group (P < 0.01) decrease. CONCLUSION: Chronically arsenic exposure can interfere the levels of serumal hormones. Arsenic has the estrogen-like effects.

Proteomic analysis of human nail plate.

Shotgun proteomic analysis of the human nail plate identified 144 proteins in samples from Causcasian volunteers. The 30 identified proteins solubilized by detergent and reducing agent, 90% of the total nail plate mass, were primarily keratins and keratin associated proteins. Keratins comprised a majority of the detergent-insoluble fraction as well, but numerous cytoplasmic, membrane, and junctional proteins and histones were also identified, indicating broad use by transglutaminases of available proteins as substrates for cross-linking. Two novel membrane proteins were identified, also found in the hair shaft, for which mRNAs were detected only at very low levels by real-time polymerase chain reaction in other tissues. Parallel analyses of nail samples from volunteers from Inner Mongolia, China gave essentially the same protein profiles. Comparison of the profiles of nail plate and hair shaft from the latter volunteers revealed extensive overlap of protein constituents. Analyses of samples from an arsenic-exposed population revealed few proteins whose levels were altered substantially but raised the possibility of detecting sensitive individuals in this way.

Global gene expression profiling of hyperkeratotic skin lesions from inner Mongolians chronically exposed to arsenic.

The skin is an organ that is highly sensitive to chronic arsenic (As) exposure. Skin lesions such as hyperkeratoses (HKs) are common early manifestations of arsenicosis in humans. HKs can be precursor lesions of nonmelanoma skin cancers (NMSCs), but the driving forces behind their formation and how they may ultimately progress to NMSCs are unknown. The goal of this study was to examine the global gene expression profiles of As-related HKs in an effort to better understand gene expression changes that are potentially associated with early stages of As carcinogenesis. HK biopsies were removed from individuals living in an arsenicosis-endemic region in Inner Mongolia who had been exposed to high As levels in their drinking water for >20 years. Gene expression profiling was performed on RNA isolated from 7 individuals in this group and from 4 lesion-free skin samples from healthy individuals. Consistent with the pathological characteristics of the HK lesions, major functional categories and known canonical pathways represented by altered transcripts include those involved in development, differentiation, apoptosis, proliferation, and stress response. The results of this study may help define a signature profile of gene expression changes associated with long-term As exposure in the skin.

Elevated ERCC1 gene expression in blood cells associated with exposure to arsenic from drinking water in Inner Mongolia.

BACKGROUND: Chronic arsenic exposure has been associated with human cancer. The objective of this study was to investigate the effects of arsenic exposure on a DNA nucleotide excision repair gene, ERCC1, expression in human blood cells. PATIENTS AND METHODS: Water and toenail samples were collected from a total of 327 Inner Mongolian residents for arsenic analysis. Blood samples were collected to determine mRNA expression levels by real-time PCR. RESULTS: The mRNA levels of ERCC1 expression were positively associated with water arsenic concentration (slope=0.313, p=0.0043) and nail arsenic concentration (slope=0.474, p=0.0073). mRNA levels of ERCC1 expression were significantly correlated with those of OGG1, a base pair excision repair gene (r=0.275, p<0.0001). CONCLUSION: The results showed that mRNA levels of ERCC1 expression were significantly associated with arsenic concentrations in drinking water, implicating the DNA repair response was induced by arsenic exposure.