Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway.

OBJECTIVE: Keshan disease (KD) is a myocardial mitochondrial disease closely related to insufficient selenium (Se) and protein intake. PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body. This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury. METHODS: A low Se and low protein animal model was established. One hundred Wistar rats were randomly divided into 5 groups (control group, low Se group, low protein group, low Se + low protein group, and corn from KD area group). The JC-1 method was used to detect the mitochondrial membrane potential (MMP). ELISA was used to detect serum creatine kinase MB (CK-MB), cardiac troponin I (cTnI), and mitochondrial-glutamicoxalacetic transaminase (M-GOT) levels. RT-PCR and Western blot analysis were used to detect the expression of PINK1, Parkin, sequestome 1 (P62), and microtubule-associated proteins1A/1B light chain 3B (MAP1LC3B). RESULTS: The MMP was significantly decreased and the activity of CK-MB, cTnI, and M-GOT significantly increased in each experimental group (low Se group, low protein group, low Se + low protein group and corn from KD area group) compared with the control group (P<0.05 for all). The mRNA and protein expression levels of PINK1, Parkin and MAP1LC3B were profoundly increased, and those of P62 markedly decreased in the experimental groups compared with the control group (P<0.05 for all). CONCLUSION: Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

Prevalence of hypertension in endemic and non-endemic areas of Keshan disease: A cross-sectional study in rural areas of China.

Background: Hypertension is a major public health concern that strongly influences the quality of life of people worldwide. Keshan disease (KD) is an endemic cardiomyopathy related to low selenium, threatening residents in rural areas of 16 provinces in China. Furthermore, the prevalence of hypertension in the KD-endemic areas has been increasing annually. However, hypertension research associated with KD has only focused on endemic regions, and no studies have compared hypertension prevalence between endemic and non-endemic areas. Therefore, this study investigated the prevalence of hypertension to provide a basis for preventing and controlling hypertension in the KD-endemic areas, even in rural areas. Methods: We extracted blood pressure information from cardiomyopathy investigation data from a cross-sectional study of the KD-endemic and non-endemic areas. The hypertension prevalence between the two groups was compared using the Chi-square test or Fisher s exact test. Additionally, Pearson's correlation coefficient was employed to evaluate the relationship between the per capita gross domestic product (GDP) and hypertension prevalence. Results: There was a statistically significant increase of hypertension prevalence in the KD-endemic areas (22.79%, 95% confidence interval [CI]: 22.30-23.27%) over the non-endemic areas (21.55%, 95% CI: 21.09-22.02%). In the KD-endemic areas, more men had hypertension than women (23.90% vs. 21.65%, P < 0.001). Furthermore, the hypertension prevalence was higher in the north than in the south in the KD-endemic areas (27.52% vs. 18.76%, P < 0.001), non-endemic areas (24.86% vs. 18.66%, P < 0.001), and overall (26.17% vs. 18.68%, P < 0.001). Finally, the prevalence of hypertension positively correlated with per capita GDP at province level. Conclusions: The increasing hypertension prevalence is a public health problem in the KD-endemic areas. Healthy diets, such as high consumption of vegetables and seafoods, and foods that are rich in selenium, might help prevent and control hypertension in the KD-endemic areas and other rural areas in China.

LncCat: An ORF attention model to identify LncRNA based on ensemble learning strategy and fused sequence information.

Background: Long non-coding RNA (lncRNA) is one of the most essential forms of transcripts, playing crucial regulatory roles in the development of cancers and diseases without protein-coding ability. It was assumed that short ORFs (sORFs) in lncRNA were weak to translate proteins. However, recent research has shown that sORFs can encode peptides, which increases the difficulty to identify lncRNA. Therefore, identifying lncRNAs with sORFs facilitates finding novel regulatory factors. Results: In this paper, we propose LncCat for identifying lncRNA based on category boosting (CatBoost) and ORF-attention features. LncCat combines five types of features to encode transcript sequences and employs CatBoost to build a prediction model. In addition, the visualization comparison reveals that the ORF-attention features between lncRNAs and protein-coding transcripts are significantly distinct. The comparison results show that LncCat outperforms competing methods on several benchmark datasets. For Matthew's Correlation Coefficient (MCC), LncCat achieves 0.9503, 0.9219, 0.8591, 0.8672, and 0.9047 on the human, mouse, zebrafish, wheat, and chicken datasets, with improvements ranging from 1.90% to 7.82%, 1.49-17.63%, 6.11-21.50%, 3.02-51.64% and 5.35-26.90%, respectively. Moreover, LncCat dramatically improves the MCC by at least 11.90%, 12.96% and 42.61% on sORF test datasets of human, mouse, and zebrafish, respectively. Conclusions: Experiments indicate that LncCat performs better both on long ORF and sORF datasets, and ORF-attention features show positive effects on predicting lncRNA. In brief, LncCat is a reliable method for identifying lncRNA. Additionally, a user-friendly web server is developed for academics at http://cczubio.top/lnccat.

Environment and chronic disease in rural areas of Heilongjiang, China (ECDRAHC).

PURPOSE: Environmental factors such as long-term exposure to cold can increase the risk of chronic diseases. However, few studies have focused on the impact of environmental factors and lifestyle changes on chronic diseases. To fully explore the association between exposure to environmental factors and the prevalent risk of various chronic diseases, we conducted a large cohort study (Environment and Chronic Disease in Rural Areas of Heilongjiang, China (ECDRAHC)). The ECDRAHC collected detailed questionnaire data covering 10 sections, physical measurements and blood and urine samples. In this study, we describe the design and implementation of the cohort study and present the findings for the first 10 000 participants. PARTICIPANTS: The ECDRAHC study was carried out in rural areas where the annual average temperature is 2.9°C, and aimed to recruit 40 000 participants who are long-term residents aged 35-74 years. The participants will be followed up every 5 years. Currently, ECDRAHC has reached 26.7% (n=10 694) of the targeted population. FINDINGS TO DATE: A total of 10 694 adults aged 35-74 years were recruited, including 61.7% women. The prevalence of current smokers was 46.8% in men and 35.4% in women. The mean blood pressure was 140.2/89.9 mm Hg and 135.7/85.0 mm Hg in men and women, respectively. The mean body mass index was 24.74 kg/m2 in men and 24.65 kg/m2 in women, with >7.3% being obese (>30 kg/m2). The main non-communicable diseases found in phase 1 were hypertension, diabetes, hypertriglyceridaemia and metabolic syndrome, with a higher prevalence of 51.0%, 21.6%, 46.8% and 42.6%, respectively. FUTURE PLANS: We plan to complete the follow-up for the first phase of the ECDRAHC in 2024. The second and third phase of the cohort will be carried out steadily, as planned. This cohort will be used to investigate the relationship between environmental factors, lifestyle, and genetic and common chronic diseases.

Study on primary physicochemical characteristics and nutrient adsorption of four plant cultivation substrates.

The primary physicochemical characteristics and the nutrient adsorption of different substrates were carried out, to select suitable cultivation substrates for plant cultivation in space. Four types of plant cultivation substrates (Profile substrate (P), black ceramsite (B), white ceramsite (W), and vermiculite (V)) were used to test and compare the primary physicochemical characteristics, such as micropore, bulk density, total porosity, specific surface area and available nutrient content, as well as the nutrients adsorption for NH4+, NO3-, PO43- and K+ with seven concentration gradients respectively. Substrate P contained more micropores, with higher parameter values of total porosity, cation exchange capacity, electrical conductivity, and specific surface area, moderate bulk density and pH, and more mineral nutrients such as potassium, magnesium, and sulfur; substrate B was porous, with smaller parameter values of total porosity, cation exchange capacity and specific surface area, minimum electrical conductivity, moderate bulk density, alkaline and smaller content of mineral elements (excepting for calcium); substrate W had smaller micropore size, the highest value of bulk density and contents of NO3- and PO43-. Other physicochemical parameters were equivalent to those of substrate B; substrate V was flaky, with the smallest values of bulk density, and the highest values of total porosity and cation exchange capacity. The values of electrical conductivity and specific surface area were smaller than those of substrate P. It contained more mineral nutrients of calcium and sulfur. Substrate V had the highest adsorption capacity for NH4+, NO3-, PO43- and K+, followed by substrate P, while substrate B and substrate W had relatively weak adsorption capacity. The adsorption capacity of four substrates for cations (NH4+ and K+) was significantly higher than that for anions (NO3- and PO43-). The orders of average adsorption amount for NH4+, NO3-, PO43- and K+ by four substrates were respectively: V > P > B > W, P > V > W > B, V > P > B > W and V > P > W > B. In comparison, substrate P and substrate V had better physicochemical characteristics, and stronger adsorption capacity for NH4+, NO3-, PO43-, and K+.

Hair Selenium of Residents in Keshan Disease Endemic and Non-endemic Regions in China.

Few nationwide investigations on hair selenium (Se) and Keshan disease (KD) have been conducted. KD is closely associated with Se deficiency. Hair Se is an important biomarker for selenium nutrition. This research aimed to provide evidence for assessment of KD prevention, control, and elimination at the molecular level from the etiological perspective of selenium nutrition. The hair Se of the residents living in the KD endemic and non-endemic areas were determined through atomic fluorescence spectrometer. The median of the hair Se levels of the inhabitants living in KD endemic counties was significantly lower than that in KD non-endemic counties (0.34 vs 0.39 mg/kg, U = -10.03, P < 0.0001). The proportion of Se-deficient or Se-marginal residents in KD endemic counties was significantly higher than that in KD non-endemic counties (56.9% vs 36.6%, U = -9.57, P < 0.0001). The medians of the hair Se levels in KD endemic provinces of Shannxi, Heilongjiang, and Gansu were the lowest (0.35mg/kg), and in the category of Se-marginal status. The hair Se level featured a positive Spearman correlation with per capita disposable income (rs = 0.20, P < 0.0001). In conclusion, the median of the hair Se contents of residents living in KD endemic counties was significantly lower than that in KD non-endemic counties. The hair Se contents of nearly 57% of inhabitants living in KD endemic regions were in Se-deficient or Se-marginal status. The KD endemic provinces of Shannxi, Heilongjiang, and Gansu should be given high priority in KD prevention and control.

A county-level spatial epidemiological study of hair selenium and Keshan disease.

Background: No spatial analysis of hair selenium and Keshan disease (KD) on a nationwide county-level has been performed. Selenium deficiency is a recognized environmental risk factor for KD. Hair selenium is one of the recognized biomarkers of selenium nutrition. This study aimed to perform a geographically precise and visualized assessment of the achievement of KD prevention and control at the level of selenium nutrition in terms of etiology. Methods: A spatial ecological study was conducted. The hair selenium content of the residents was assayed using an atomic fluorescence spectrometer. The spatial analysis was performed using ArcGIS. Results: The median of the hair selenium levels of the 3,028 participants in the 1,174 counties was 0.38 mg/kg, and the content of inhabitants in KD endemic counties was significantly lower than that in KD non-endemic counties (0.34 vs. 0.39 mg/kg, z = -10.03, P < 0.0001). The proportion of Se-deficient and Se-marginal counties in KD endemic counties was significantly higher than that in KD non-endemic counties (59.4 vs. 29.0%, z = -7.45, P < 0.0001). The global autocorrelation analysis was not statistically significant (Moran's I = 0.0005, P = 0.68). Local autocorrelation analysis identified 174 low-low clusters of hair selenium levels, 83 (47.7%) of which are KD endemic counties located in KD endemic provinces of Henan, Gansu, Shaanxi, Inner Mongolia, Jilin, and Heilongjiang. The hair selenium featured a positive correlation with per capita GDP (r s = 0.20, P < 0.0001). Conclusion: The median of the hair selenium levels of inhabitants living in KD endemic counties was significantly lower than that in KD non-endemic counties. All the 83 KD endemic counties with low-low clusters of hair selenium levels should be prioritized in KD precision prevention and control. These findings are geographically precise and visualized evidence of the assessment of the effectiveness of KD prevention and control at the level of selenium nutrition in terms of etiology.

Evaluation of Risk Factors for Chronic Obstructive Pulmonary Disease in the Middle-Aged and Elderly Rural Population of Northeast China Using Logistic Regression and Principal Component Analysis.

Purpose: To investigate the environmental, immune, and inflammatory factors associated with chronic obstructive pulmonary disease (COPD) in middle-aged and older Chinese individuals. Patients and Methods: A community-based case-control study was conducted among 471 patients with COPD and 485 controls. The information on COPD of the participants was collected through face-to-face interviews, and serum samples were measured at the laboratory. The main risk factors for COPD were analyzed using principal component analysis (PCA) and logistic regression. Results: Nine hundred and fifty-six respondents were included in the analysis. The results of the PCA-logistic regression analysis showed significant differences in the environmental factors, medical history, and serum C-reactive protein (CRP) levels between patients and controls. COPD was markedly more usual in those with smoking index >200 (OR, 1.42; 95% CI, 1.28-1.57); exposure to outdoor straw burning (OR, 1.64; 95% CI, 1.47-1.83); use of coal, wood, and straw indoors (OR, 2.31; 95% CI, 1.92-2.78); history of respiratory disease and coronary heart disease (OR, 3.58; 95% CI, 3.12-4.10), congestive heart failure (OR, 1.23; 95% CI, 1.09-1.38), and cerebrovascular disease (OR, 1.15; 95% CI,1.02-1.31); and higher serum level of CRP (OR, 1.20; 95% CI, 1.11-1.30). Compared to the logistic regression analysis, PCA logistic regression analysis identified more important risk factors for COPD. Conclusion: PCA-logistic regression analysis was first utilized to explore the influencing factors among rural residents in Northeast China Environmental aged 40 years and above, it was found that environmental factors, medical history, and serum CRP levels mainly affected the prevalence of COPD.

A County-Level Spatial Study of Serum Selenoprotein P and Keshan Disease.

BACKGROUND: Keshan disease (KD) is strongly associated with selenium deficiency. Selenoprotein P (SELENOP) is a recognized molecular biomarker of selenoproteins and an important indicator of selenium nutrition. This study was aimed at providing geographically precisely visualized evidence of selenium nutrition at molecular level for assessing KD prevention, control, and elimination on the etiological perspective. METHODS: We used spatial ecological design for this study. The serum SELENOP levels of the residents were measured by ELISA. ArcGIS version 9.0 was used for spatial description, spatial autocorrelation analysis of SELENOP levels and spatial regression with per capita disposable income. RESULTS: The mean serum SELENOP levels of the 6,382 residents in 1,688 counties were 4.62 ± 1.82 µg/mL. The mean serum SELENOP levels of the residents living in the townships and rural areas of KD endemic counties were not statistically significantly lower than those of the KD non-endemic counties. The mean serum SELENOP levels were globally clustered (Moran's I = 0.03, z = 6.37, and P < 0.0001), and 99.3% (553/557) of the cold spots, identified by local autocorrelation analysis (Getis-Ord-Gi* analysis), were located in the KD endemic provinces of Shaanxi, Shanxi, Henan, Hebei, Shandong, Inner Mongolia, Gansu, Hubei, Chongqing, Yunnan, and Sichuan. The serum SELENOP level was positively correlated with per capita disposable income (t = 3.52, P = 0.0004). CONCLUSIONS: The results of this study were the geographically precisely visualized evidence of selenium nutrition at molecular level for assessing KD elimination on the etiological perspective. The cold spot counties found by Getis-Ord-Gi* analysis in the KD endemic provinces should be the high priority of KD precision prevention and control.

Association of selenium levels with the prevention and control of Keshan disease: A cross-sectional study.

PURPOSE: The prevalence of Keshan disease (KD) is low and has reached controlled or eliminated levels even in counties that had a high KD prevalence in the past. Few nationwide surveys on selenium levels in KD areas have been conducted in the past 2 decades. We conducted a cross-sectional study to investigate the selenium levels and their association with KD control and prevention in areas where KD is prevalent. METHODS: We collected 2143 human-hair, 698 soil, 701 rice, 607 flour, 521 corn, and 330 other-food samples from 49 counties with KD and 19 non-KD counties of nine KD provinces of China. The selenium content of samples was examined with hydride generation atomic fluorescence spectrometry. The difference in selenium levels between the KD and non-KD areas was analyzed. Cochran-Armitage trend tests were used to evaluate the association between selenium levels and KD control. RESULTS: The selenium levels in human hair, soil, staple foods, and other foods in the KD areas (0.2996 mg/kg, 0.1380 mg/kg, 0.0190 mg/kg and 0.0076 mg/kg, respectively) were lower than those in the non-KD areas (0.3700 mg/kg, 0.1930 mg/kg, 0.0240 mg/kg and 0.0165 mg/kg, respectively). The Cochran-Armitage tests showed that there was a trend for the selenium standard ratio in the counties to increase in the order of KD uncontrolled, to controlled, to eliminated (Z = 2.229, P < 0.05). CONCLUSION: The residents in the KD areas were found to be selenium-deficient. Improving the supply of staple foods containing selenium levels exceeding 0.025 mg/kg and abundant foodstuffs might contribute to KD control and prevention.

Essential hypertension in patients exposed to high-arsenic exposed areas in western China: Genetic susceptibility and urinary arsenic metabolism characteristics.

OBJECTIVE: To clarify the urinary arsenic metabolism characteristics in individuals with essential hypertension and to analyze the relationship between lipid metabolism gene polymorphisms and susceptibility to essential hypertension in individuals in high-arsenic areas in western China. METHODS: A case-control study was conducted and involved individuals exposed to high arsenic levels (in this study, the arsenic content in the pressurized well water was 0-510.2 µg/L, and that in the mechanical well water was 167 µg/L) in two adjacent high-arsenic areas in Shanxi Province and the Inner Mongolia Autonomous Region, China. A total of 699 samples were collected, including 192 case samples (patients with hypertension) and 507 control samples (no hypertension). Blood pressure measurement data obtained from an epidemiological survey were used to determine whether the subjects had hypertension, and a logistic regression model was used to analyze the association between lipid metabolism gene polymorphisms and hypertension susceptibility. Blood and urine samples were collected based on epidemiological methods, single nucleotide polymorphisms (SNPs) were genotyped using a SNPscan™ multiple SNP typing kit, and urinary arsenic concentrations were determined using the hydride generation atomic fluorescence method (HG-AFS). RESULTS: ADIPOQ/rs266729 was the dominant genetic model [(GC + GG) vs CC = 0.686:1, 95 % CI = 0.478-0.983], and FABP2/rs1799883 was the recessive genetic model [TT vs (CC + TC) = 1.690:1, 95 % CI = 1.014-2.816]. The distribution of the urinary arsenic secondary methylation ratio (SMR) [dimethylated arsenic (DMA)/monomethylated arsenic (MMA)] was different between hypertensive patients and controls. CONCLUSION: ADIPOQ/rs266729 and FABP2/rs1799883 polymorphisms affect susceptibility to essential hypertension in individuals exposed to high levels of arsenic; there was a clear difference in the urinary arsenic metabolism pattern between hypertensive patients and controls.

Effects of selenium deficiency and low protein intake on the apoptosis through a mitochondria-dependent pathway.

OBJECTIVE: Selenium(Se)is an important trace element for human health. Studies have shown that selenium deficiency and low protein(Pr) intake are the primary risk factors for Keshan disease.The relationship between the cardiac malfunction induced by these two risk factors and the mitochondria-mediated apoptotic pathway is poorly understood.This study aimed to determine the effect of selenium deficiency and low protein intake on the mitochondria-mediated apoptotic pathway. METHODS: In the present study, 120 weaning Wistar rats were randomly fed one of six different diets. The myocardial tissue sections were deparaffinized in water and subjected to hematoxylin-eosin staining. Mitochondrial changes in the myocardial tissue were observed and photographed using an H-7650 Hitachi transmission electron microscope. Levels of whole blood Se were measured using hydride generation atomic fluorescence spectrometry. Whole blood glutathione peroxidase (GSH-Px) activity was measured using a glutathione peroxidase cellular activity assay kit. Malondialdehyde (MDA), total-anti-oxidizing-capability(T-AOC)and reactive oxygen species(ROS)levels in serum and myocardial tissue were measured using MDA, T-AOC and ROS kits. Apoptosis was detected by immunohistochemistry. RESULTS: Experimental results showed that the selenium-deficient diet decreased serum selenium levels and GSH-PX activity, which caused severe cardiac dysfunction. Importantly, the levels of MDA and ROS in serum and myocardial tissue defects were significantly increased, where as total-anti-oxidizing-capability(T-AOC) levels were dramatically decreased as a result of the combination of selenium deficiency and low protein intake (P<0.05).The levels of cleaved caspase-9 and cleaved caspase-3 were enhanced, but the expression of B-cell lymphoma-2 (Bcl-2) was reduced (P<0.05). CONCLUSIONS: Our results suggest that selenium deficiency and low protein intake can cause oxidative stress in the myocardium and induce cell apoptosis via the mitochondria-mediated pathway.

Impact of main vessel calcification on procedural and clinical outcomes of bifurcation lesion undergoing provisional single-stenting intervention: a multicenter, prospective, observational study.

BACKGROUND: Few data on the combined effects of bifurcation and calcification on coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) are available. This study evaluated the impact of main vessel (MV) calcification on the procedural and long-term outcomes in patients with CAD who underwent provisional single stent PCI. METHODS: This is a multicenter, prospective, observational study. Patients with bifurcation lesions were enrolled at 10 PCI centers in China from January 2015 to December 2017. Intravascular ultrasound or optical coherence tomography was performed in all patients to evaluate the MV calcification. Patients were treated with provisional single stent strategy using drug eluting stents and followed-up at 1 month, 6 months and 12 months after discharge by telephone contact or outpatient visit. Repeated coronary imaging was performed within one year. We compared the procedural success rates in MV and in side branch (SB), and target lesion failure (TLF), defined as a composite of cardiac death, non-fatal myocardial infarction, definite or possible stent thrombosis and target lesion revascularization between patients with and without MV calcification. RESULTS: A total of 185 subjects were enrolled according to the inclusion and exclusion criteria of this study. MV calcification was detected in 119 (64.3%, calcification group) and not found in 66 (35.7%, non-calcification group) patients. The angiographic success rate of MV was 95.8% in the calcification group and 97.0% in the non-calcification group (P = 0.91); the angiographic success rate of SB was 32.8% in the calcification group and 53.0% in the non-calcification group (P < 0.05). During the one-year follow-up period, TLF occurred in 14 (11.8%) patients in the calcification group and in 13 (19.7%) in the non-calcification group (P = 0.31). Multivariate regression analysis showed the same result (HR = 1.23, 95% CI: 0.76-1.52, P = 0.47). Calcification on group had higher recurrent angina than non-calcification group (13.51% vs. 17.65%, P < 0.05). CONCLUSIONS: In patients with coronary bifurcation lesion treated with provisional one stent approach, calcification of MV is associated with lower SB procedural success rate, it could increase recurrence of angina; however, it was not associated with an increased risk of TLF.

Factors Affecting Differential Methylation of DNA Promoters in Arsenic-Exposed Populations.

The exposure/biotransformation of inorganic arsenic (iAs) may perturb DNA methylation patterns and subsequently influence disease risk by altering the expression of key genes. Interindividual variation in patterns of DNA methylation can be explained by the influence of environmental, genetic, and stochastic factors. Here, we examined promoter DNA methylation levels with urinary arsenical concentrations and investigated the genetic and nongenetic determinants of DNA methylation in 105 samples collected from populations in Shanxi Province, China, with high levels of arsenic in drinking water. Arsenic concentrations in water were determined by atomic absorption spectrophotometry (AA-6800, Shimadzu Co., Kyoto, Japan). Urine samples were measured using an atomic absorption spectrophotometer with an arsenic speciation pretreatment system (ASA-2sp, Shimadzu Co. Kyoto, Japan) for detection. Gene-specific (CDH1, EREG, ERCC2, GSTP1, and MGMT) DNA methylation was quantified by targeted bisulfite sequencing. Single-nucleotide polymorphism (SNP) genotyping was performed using a custom-by-design 2 × 48-Plex SNPscan™ Kit. These results revealed CDH1 with promoter DNA methylation levels associated with iAs. After the exclusion of confounding factors, age was correlated with increased methylation of the CDH1 gene. The susceptibility of the CDH1 and GSTP1 gene promoters to methylation was increased in individuals carrying the DNMT3B (SNP rs2424932) GA genotype, and the susceptibility of the CDH1 gene promoters to methylation was increased in individuals carrying the DNMT3B (SNP rs6087990) TC genotype. Although the above results must still be replicated in larger samples, the findings improve our understanding of the pathogenesis of arsenic and may highlight certain DNA methylation markers as attractive surrogate markers for prevention research.

Association between arsenic metabolism gene polymorphisms and arsenic-induced skin lesions in individuals exposed to high-dose inorganic arsenic in northwest China.

Individuals in a given environment contaminated with arsenic have different susceptibilities to disease, which may be related to arsenic metabolism, age, gender, genetics and other factors. This study recruited 850 subjects, including 331 cases and 519 controls, from populations exposed to high levels of arsenic in drinking water in northwest China. Genotypes were determined using a custom-by-design 48-Plex SNPscanTM kit. The results indicated that subjects who carried at least one C allele for GSTO1 rs11191979 polymorphism, at least one A allele for GSTO1 rs2164624, at least one A allele for GSTO1 rs4925, the AG genotype for GSTO2 rs156697, the AG genotype or at least one G allele for GSTO2 rs2297235 or the GG genotype or at least one G allele for PNP rs3790064 had an increased risk of arsenic-related skin lesions. In addition, the haplotype CT between rs4925 and rs11191979 appeared to confer a high risk of arsenic-included skin lesions (OR = 1.377, 95% CI = 1.03-1.84), as did the haplotype GCG among rs156697, rs157077 and rs2297235 (OR = 2.197, 95% CI = 1.08-4.44). The results showed that the variants of GSTO1, GSTO2 and PNP render the susceptible toward developing arsenic-induced skin lesions in individuals exposed to high-dose inorganic arsenic in northwest China.

Biomarkers of renal toxicity caused by exposure to arsenic in drinking water.

This study is intended to explore effective and sensitive biomarkers for kidney damage after low level arsenic (As) exposure and to provide scientific evidence on cut-off values of arsenic concentrations in drinking water. The levels of α1-MG detected in urine samples were found to have statistically significant differences between high As group (As>0.05 mg/L) and a combination of low and medium As exposure groups (As<0.05 mg/L, p=0.018), as well as between the patient and high As groups (As in two group were both higher than 0.05 mg/L, p<0.001). After the logistic regression analysis the AUC values of α1-MG between two comparisons were 0.613 and 0.701, and p value was less than 0.05. The present data demonstrate the potential value of α1-MG excretion as a biomarker of renal toxicity, which could contribute to the enforcement of the maximum limit of 0.05 mg/L arsenic in drinking water for non-central water supply in rural areas.

Role of pigment epithelium-derived factor (PEDF) in arsenic-induced cell apoptosis of liver and brain in a rat model.

Although studies have shown that arsenic exposure can induce apoptosis in a variety of cells, the exact molecular mechanism of chronic arsenicosis remains unclear. Based on our previous study on human serum, the present study was to determine whether pigment epithelium-derived factor (PEDF) plays a role in the damage induced by chronic arsenic exposure in a rat model and to explore the possible signaling pathway involved. Thirty male Wistar rats were randomly divided into three groups and the arsenite doses administered were 0, 10, and 50 mg/L, respectively. The experiment lasted for 6 months. Our results showed that level of arsenic increased significantly in serum, liver, brain, and kidney in arsenic-exposed groups. It was indicated that PEDF protein was widely distributed in the cytoplasm of various types of cells in liver, brain, and kidney. PEDF protein level was only changed when the arsenite dose reached 50 mg/L in liver and brain, whereas it was not changed in the kidney. In order to investigate the possible mechanism of PEDF-exerted damages upon arsenite exposure, apoptosis in liver and brain was assessed. The proportion of apoptotic cells gradually increased with increasing arsenic administration. The ratio of Bax/Bcl-2 in the high arsenic group (50 mg/L) was significantly higher than that in the control group. Therefore, we thought PEDF played a role in cell apoptosis of liver and brain which induced by sodium arsenite exposure, and the results also demonstrated that Bax and Bcl-2 might be two key targets in the action of PEDF.

Changes in serum thioredoxin among individuals chronically exposed to arsenic in drinking water.

It is well known that oxidative damage plays a key role in the development of chronic arsenicosis. There is a complex set of mechanisms of redox cycling in vivo to protect cells from the damage. In this study, we examined the differences in the levels of serum thioredoxin1 (TRX1) among individuals exposed to different levels of arsenic in drinking water and detected early biomarkers of arsenic poisoning before the appearance of skin lesions. A total of 157 subjects from endemic regions of China were selected and divided into arsenicosis group with skin lesions (total intake of arsenic: 8.68-45.71mg-year) and non-arsenicosis group without skin lesions, which further divided into low (0.00-1.06mg-year), medium (1.37-3.55mg-year), and high (4.26-48.13mg-year) arsenic exposure groups. Concentrations of serum TRX1 were analyzed by an ELISA method. Levels of water arsenic and urinary speciated arsenics, including inorganic arsenic (iAs), monomethylated arsenic (MMA), and dimethylated arsenic (DMA), were determined by hydride generation atomic absorption spectrometry. Our results showed that the levels of serum TRX1 in arsenicosis patients were significantly higher than that of the subjects who were chronically exposed to arsenic, but without skin lesions. A positive correlation was seen between the levels of serum TRX1 and the total water arsenic intake or the levels of urinary arsenic species. The results of this study indicate that arsenic exposure could significantly change the levels of human serum TRX1, which can be detected before arsenic-specific dermatological symptoms occur. This study provides further evidence on revealing the mechanism of arsenic toxicity.

Risk factors for neurodevelopmental deficits in congenital hypothyroidism after early substitution treatment.

Neurodevelopment in children with congenital hypothyroidism who receive early treatment is generally good. However, subtle neurological deficits still exist in some patients. The aim of this investigation was to evaluate factors that may influence neurodevelopmental outcome in congenital hypothyroidism patients. The developmental quotient (DQ) of 155 children with congenital hypothyroidism was evaluated at 24 months of age, using Gesell Developmental Schedules (GDS), and compared with that of 310 healthy controls. Mean DQ scores in congenital hypothyroidism patients were 7.5 points lower for adaptive behavior than in control patients (p < 0.01). Patients with severe congenital hypothyroidism had the lowest DQ scores compared with two other congenital hypothyroidism subgroups and controls (p < 0.01). Children with congenital hypothyroidism who also had a low level of serum T(4) at diagnosis or exhibited a longer thyroid stimulating hormone (TSH) normalization time had lower adaptive behavior scores (p < 0.0003). Bivariate correlation and multiple regression analyses found that the severity of congenital hypothyroidism and parental socioeconomic status correlated with DQ scores. TSH normalization time was negatively related to adaptive behavior scores (p < 0.01). Neurodevelopmental deficits in children with congenital hypothyroidism correlate with the severity of congenital hypothyroidism, TSH normalization time, and parental socioeconomic status.

Suboptimal selenium supply--a continuing problem in Keshan disease areas in Heilongjiang province.

This study explores whether the declining prevalence of Keshan disease is associated with increasing selenium levels in Keshan disease areas in Heilongjiang province. Six counties endemic with Keshan disease and three non-endemic counties were selected as study areas. In each county, two townships and in each township one village were chosen in which to survey ten families about head hair, grain, and soil samples and to obtain demographic information. Selenium was measured with hydride generation-atomic fluorescence spectrometry. In each county endemic with Keshan disease, one of the villages was chosen to investigate the prevalence of the disease. We collected 534 head hair samples, 446 staple food samples, and 180 soil samples. The selenium levels of head hair and corn in the endemic counties were significantly lower than those in non-endemic counties. Family demographic information was homologous except for the composition of staple food. More residents in Keshan disease areas preferred flour and corn. The detection rate for latent Keshan disease had a significantly negative correlation with the corn selenium level in six counties endemic with Keshan disease. As the population in this region is still at risk for Keshan disease, selenium surveillance measures should be intensified.