Customizable Zr-MOF nanoantidote-based multieffective arsenic detoxification and its extended low-toxic therapy.

Arsenic (As) poisoning has become a global public problem threatening human health. Chelation therapy (CT) is the preferred treatment for arsenic poisoning. Nevertheless, efficient and safe arsenic removal in vivo remains a daunting challenge due to the limitations of chelators, including weak affinity, poor cell membrane penetration, and short half-life. Herein, a mercapto-functionalized and size-tunable hierarchical porous Zr-MOF (UiO-66-TC-SH) is developed, which possesses abundant arsenic chemisorption sites, effective cell uptake ability, and long half-life, thereby efficiently removing toxic arsenic in vivo. Moreover, the strong binding affinity of UiO-66-TC-SH for arsenic reduces systemic toxicity caused by off-target effects. In animal trials, UiO-66-TC-SH decreases the blood arsenic levels of acute arsenic poisoning mice to a normal value within 48 h, and the efficacy is superior to clinical drugs 2,3-dimercaptopropanesulfonic acid sodium salt (DMPS). Meanwhile, UiO-66-TC-SH also significantly mitigates the arsenic accumulation in the metabolic organs of chronic arsenic poisoning mice. Surprisingly, UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates the side effects of arsenic drugs antitumor therapy. STATEMENT OF SIGNIFICANCE: Arsenic (As) contamination has become a global problem threatening public health. The present clinical chelation therapy (CT) still has some limitations, including the weak affinity, poor cell membrane permeability and short half-life of hydrophilic chelators. Herein, a metal-organic framework (MOF)-based multieffective arsenic removal strategy in vivo is proposed for the first time. Mercapto-functionalized and size-tunable hierarchical porous Zr-MOF nanoantidote (denoted as UiO-66-TC-SH) is accordingly designed and synthesized. After injection, UiO-66-TC-SH can form Zr-O-As bonds and As-S bonds with arsenic, thus enhancing arsenic adsorption capacity, cycling stability and systemic safety simultaneously. The acute arsenic poisoning model results indicate that UiO-66-TC-SH shows superior efficacy to the clinical drug sodium dimercaptopropanesulfonate (DMPS). More meaningfully, we find that UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates side effects of arsenic drugs anti-tumor therapy.

Environmental arsenic pollution induced liver oxidative stress injury by regulating miR-155 through inhibition of AUF1.

Arsenic (As), a common environmental pollutant, has become a hot topic in recent years due to its potentially harmful effects. Liver damage being a central clinical feature of chronic arsenic poisoning. However, the underlying mechanisms remain unclear. We demonstrated that arsenic can lead to oxidative stress in the liver and result in structural and functional liver damage, significantly correlated with the expression of AUF1, Dicer1, and miR-155 in the liver. Interestingly, knockdown AUF1 promoted the up-regulatory effects of arsenic on Dicer1 and miR-155 and the inhibitory effects on SOD1, which exacerbated oxidative damage in rat liver. However, overexpression of AUF1 reversed the up-regulatory effects of arsenic on Dicer1 and miR-155, restored arsenic-induced SOD1 depletion, and attenuated liver oxidative stress injury. Further, we verified the mechanism and targets of miR-155 in regulating SOD1 by knockdown/overexpression of miR-155 and nonsense mutant SOD1 3'UTR experiments. In conclusion, these results powerfully demonstrate that arsenic inhibits AUF1 protein expression, which in turn reduces the inhibitory effect on Dicer1 expression, which promotes miR-155 to act on the SOD1 3'UTR region after high expression, thus inhibiting SOD1 protein expression and enzyme activity, and inducing liver injury. This finding provides a new perspective for the mechanism research and targeted prevention of arsenic poisoning, as well as scientific evidence for formulating strategies to prevent and control environmental arsenic pollution.

Assessing the mechanisms and adjunctive therapy for arsenic-induced liver injury in rats.

Environmental arsenic exposure is a significant global public health concern. Previous studies have demonstrated the association between arsenic-induced liver injury and oxidative stress as well as ferroptosis. However, the knowledge of the interactions among these mechanisms remains limited. Moreover, there is a lack of research on potential therapeutic interventions for liver injury resulting from arsenic exposure. To address these limitations, we established a rat model with liver injury caused by arsenic exposure and investigated the impact of the nuclear factor E2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPx4) signaling pathway and ferroptosis on arsenic-induced liver injury. Our findings revealed that arsenic increased Nrf2 expression and decreased GPx4 expression in the rat liver. This was accompanied by a substantial generation of reactive oxygen species and disruption of the antioxidant defense system, ultimately promoting liver injury through ferroptosis. Subsequently, we conducted intervention experiments using Rosa roxburghii Tratt (RRT) in rats exposed to arsenic. The results showed that the detrimental effects mentioned earlier were partially alleviated following RRT intervention. This study offers preliminary evidence that persistent activation of Nrf2 by arsenic triggers an adaptive antioxidant response, leading to liver injury through the promotion of ferroptosis. Additionally, we discovered that RRT inhibits Nrf2-mediated adaptive antioxidant responses by reducing hepatic ferroptosis, thereby mitigating liver injury caused by arsenic exposure in rats. Our study contributes to a deeper understanding of the molecular mechanisms underlying liver injury resulting from arsenic exposure. Furthermore, our findings may facilitate the identification of a potential edible and medicinal plant extracts that could be utilized to develop a more effective adjunctive treatment approach.

The Hepatorenal Protective Potential of Caffeic Acid Consumption on the Arsenic-Exposed Syrian Mice.

Arsenic can induce lethal hepatorenal insufficiency by inducing progressive cytotoxicity in the two main body's hemostatic regulators, the kidney and liver. In the current study, the hepatorenal protective impact of caffeic acid was investigated in arsenic-exposed Syrian mice. Twenty-four male Syrian mice (30 ± 8 g) were provided and randomly divided into 4 groups of 6 receiving nothing, arsenic, arsenic and caffeic, and caffeic acid. The mice passed the 21-day treatment program. The mice's blood was collected and analyzed by measuring the serum ALT/AST enzymes and creatinine/urea levels, respectively. Finally, the histopathological properties in both the kidney and liver organs of the mice were studied. Arsenic administration significantly increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), LDH, urea, and creatinine concentrations (p < 0.05). Simultaneous administration of caffeic acid with arsenic decreased the serum AST and creatinine (p < 0.05). Moreover, the renal glomerulus and liver regeneration in the mice receiving caffeic acid supplements exhibited the caffeic acid hepatorenal protective potential. The histopathological changes caused by arsenic in the mice's liver and kidney tissue including degeneration, necrosis, hyperemia, and tissue hypotrophy were shifted to normal conditions following the caffeic acid administration dose, which was verified by the mice blood biochemical analysis results.

Four cases of fatal acute arsenic poisoning: histopathology, toxicology, and new trends.

Arsenic is a valuable component in tumor treatment and traditional Chinese medicine and has seen widespread use in processing, manufacturing, and agriculture. Although rare, arsenic poisoning can occur in forensic practice. Elusive pathological changes, as well as obscure clinical signs, may cause arsenic poisoning to go unrecognized. Here, we report four cases of fatal acute arsenic poisoning, with careful observation of pathological changes and collection of postmortem specimens for arsenic concentration analysis. Additionally, we reviewed six cases of fatal arsenic poisoning in the past 20 years. In the present study, microvesicular steatosis in the peripheral areas of the hepatic lobules and acute splenitis were observed, which are rare findings in acute arsenic poisoning. This study summarizes the histopathological features of arsenic poisoning and presents data on arsenic distribution. Arsenic concentrations in the liver and kidneys can increase the reliability of identifying arsenic poisoning. Furthermore, in traditional Chinese medicine-related deaths, arsenic poisoning needs more attention.

Metal Exposure in Arica, Chile: Examining Toxic Elements / Análisis de exposición a metales en Arica, Chile: niveles de elementos tóxicos

BACKGROUND: Bioaccumulation of toxic metals in the population is associated with adverse health effects. Although some elements are essential for humans, high levels of exposure can be dangerous. OBJECTIVE: To describe the levels of Inorganic Arsenic (AsIn), Cadmium (Cd), Chromium (Cr), and Mercury (Hg) in urine, and Lead (Pb) in blood in the population of Arica, Chile. METHODOLOGY: Descriptive study. Beneficiaries of the Health Surveillance Program of Law 20.590 in sites of higher risk of exposure in the commune of Arica were considered eligible. The results of biological samples to measure their concentrations of AsIn, Cd, Cr, Hg in urine, and Pb in blood between August 2016 and May 2021 are described. RESULTS: 9520 samples from a population with a mean age of 40.5 years were studied. 4.21% of the adult population and 6.57% of the children had AsIn values above 35 μg/L, while at least 95 % of the total samples had levels below 33 μg/L. At least 90 % of the samples had Cd levels below 1.1 μg/L, and 8.44 % had Cd levels above 2 μg/L, higher in males (11.67%). There were no values above the reference in children. 99.77% and 99.33% had Cr and Pb values below the reference limit, respectively (using the lowest reference range established by Chile Ministry of Health (MINSAL) < 5 μg/L). Children did not present risk values for Cr, and 0.16% presented Pb concentrations between 5-10 μg/dL. All samples presented Hg concentrations below risk levels (< 10 μg/L). CONCLUSIONS: The results of this study suggest that a small percentage of the samples analyzed in the beneficiary population of Arica register metal concentration levels above national reference levels established by MINSAL, mainly AsIn, Cd, and Pb. It is essential to continue biomonitoring to reduce and prevent exposure to these metals, which can have harmful effects on human health.

ANTECEDENTES: La bioacumulación de metales en la población está asociada a efectos adversos y pueden ser peligrosos. OBJETIVO: Describir los niveles de Arsénico Inorgánico (AsIn), Cadmio (Cd), Cromo (Cr), Mercurio (Hg) y Plomo (Pb) en la población de Arica, Chile. MATERIALES Y MÉTODOS: Estudio descriptivo. Se incluyeron todas las personas beneficiarias del Programa de Vigilancia de Salud de la Ley 20.590 en sitios de riesgo de mayor exposición en la comuna de Arica entre agosto 2016 y mayo 2021. RESULTADOS: Se estudiaron 9.520 muestras provenientes de una población con una edad media de 40.5 años. 4.21% de la población adulta y el 6.57% de los niños presentaron valores de AsIn superiores a 35 μg/L y al menos el 95% de las muestras totales tenía niveles inferiores a 33 μg/L. Más del 90 % de las muestras tuvieron niveles de Cd menores a 1.1 μg/L y un 8.44% registró niveles de Cd superiores 2 μg/L. El 99.77% y 99.33% exhibieron valores normales de Cr y Pb, respectivamente. Todas las muestras presentaron concentraciones de Hg por debajo de los niveles de riesgo (< 10 μg/L). CONCLUSIONES: Los resultados sugieren que un porcentaje pequeño de la población de Arica registra niveles de concentración de metales por sobre niveles de referencia nacional establecidos por el Ministerio de Salud de Chile, principalmente de AsIn, Cd y Pb. Es importante continuar con la vigilancia para reducir y prevenir la exposición a estos metales, que pueden generar efectos nocivos en la salud humana.

Arsenic in drinking water, hair, and prevalence of arsenicosis in Perak, Malaysia.

Arsenic is a carcinogen element that occurs naturally in our environment. Humans can be exposed to arsenic through ingestion, inhalation, and dermal absorption. However, the most significant exposure pathway is via oral ingestion. Therefore, a comparative cross-sectional study was conducted to determine the local arsenic concentration in drinking water and hair. Then, the prevalence of arsenicosis was evaluated to assess the presence of the disease in the community. The study was conducted in two villages, namely Village AG and Village P, in Perak, Malaysia. Socio-demographic data, water consumption patterns, medical history, and signs and symptoms of arsenic poisoning were obtained using questionnaires. In addition, physical examinations by medical doctors were performed to confirm the signs reported by the respondents. A total of 395 drinking water samples and 639 hair samples were collected from both villages. The samples were analyzed using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) to determine arsenic concentration. The results showed that 41% of water samples from Village AG contained arsenic concentrations of more than 0.01 mg/L. In contrast, none of the water samples from Village P exceeded this level. Whilst, for hair samples, 85 (13.5%) of total respondents had arsenic levels above 1 µg/g. A total of 18 respondents in Village AG had at least one sign of arsenicosis and hair arsenic levels of more than 1 µg/g. Factors significantly associated with increased arsenic levels in hair were female, increasing age, living in Village AG and smoking. The prevalence of arsenicosis in the exposed village indicates chronic arsenic exposure, and immediate mitigation action needs to be taken to ensure the wellbeing of the residents in the exposed village.

Arsenic-induced toxicity and the ameliorative role of antioxidants and natural compounds.

Arsenic (As) poisoning has proven to be a major threat worldwide because of its toxic effects on the human body. As toxicity through drinking water is a global health concern. The toxicity of As is known to affect the liver, kidney, lungs, muscles, cardiovascular system, and nervous system and can even induce diabetes. Further As can cause skin lesions leading to notable diseases in the skin like Bowen's disease. Chronic exposure to As has caused many tragedies in Eastern, and several Southeast Asian and Latin American countries. Long-term exposure to As makes it an immediate threat that should be dealt with as a priority, and one of the ways to handle it may be with the use of antioxidants. In this review, we have discussed the natural and anthropogenic sources of As, its metabolism, pathophysiology, and mechanism of toxicity. Besides, we have also discussed some of the synthetic chelators and the ameliorative role of antioxidants and natural compounds in reducing As toxicity.

Effects of Ozone Therapy on Chronic Arsenic Poisoning in Rats.

Arsenic (As) is a toxic metalloid that affects many organs through drinking water. This study aims to examine the efficacy of ozone therapy on chronic arsenic toxicity. Twenty-four male Wistar albino rats were housed in individual cages and grouped as control, As, O3, and As + O3. As was applied by adding 5 mg/kg/day in drinking water for 60 days. Ozone therapy was applied at 0.5 mg/kg/day (i.p.) O3 in the last 5 days of the experimental period. Tissues were harvested and analyzed for histopathological injury and apoptotic markers. There was no significant difference between the As + O3 and O3 groups (p = 0.186 and p = 0.599) for light microscopic criteria: inflammatory cell infiltration and hydropic degeneration in liver tissue.In TUNEL assessments, similar outcomes were obtained in the control and As + O3 groups. A statistically significant increase was observed in p53 and Caspase 3 (Casp-3) expression levels in the As group compared to the O3 and As + O3 groups. There was no significant difference between the As + O3 and O3 groups on peritubular hemorrhage and desquamation parameters in kidneys (p = 0.147 and p = 0.094). The KIM-1 expression level was significantly increased in the As group compared to the As + O3 group (p = 0.01), and the Casp-3 expression level was not significantly changed in the O3 group compared to the As + O3 group (p = 0.59). In conclusion, it is determined that ozone therapy has ameliorative effects on the microscopic injury of liver and kidney tissues. In addition to microscopic improvement, KIM-1 gene expression levels were ameliorated in the kidneys. The apoptotic cell counts and the Casp-3 and p53 gene expression levels were decreased by O3 administration. Thus, ozone therapy can be a treatment choice for As toxicity.

A survey on the prevalence and associated factors of arsenic poisoning-related skin lesions in an arsenic tailing area in Hunan Province, China / 中华皮肤科杂志

Objective:To investigate epidemiological characteristics of arsenic poisoning-related skin lesions in an arsenic tailing area in Hunan Province.Methods:A cross-sectional study was conducted. From October 2016 to January 2017, all residents aged over 18 years (except pregnant women) were enrolled from 3 villages in Baiyun Town, Shimen County, Hunan Province by using a cluster-sampling method. Demographic information was collected through a face-to-face questionnaire interview. All residents received skin examination performed by professional dermatologists, and blood, urine, and hair samples were collected for the measurement of arsenic levels. Non-conditional logistic regression analysis was performed to analyze factors associated with arsenic poisoning-related skin lesions.Results:A total of 1 092 eligible residents in the arsenic tailing area were recruited in this study, and 756 (69.2%, 95% CI: 66.5%, 72.0%) presented with arsenic poisoning-related skin lesions, including hyperkeratosis, hypo- or hyper-pigmentation. The median ( Q1, Q3) arsenic levels were 0.31 (0.14, 0.74) μg/g in hair samples ( n = 1 079), 0.84 (0.67, 1.10) μg/L in blood samples ( n =1 091), and 60.31 (41.71, 91.52) μg/L in urine samples ( n =1 092). Multivariable analysis showed that the occurrence of arsenic poisoning-related skin lesions was associated with age, residential location, and occupational arsenic exposure history, but was not associated with gender, ethnicity, education levels, migration history, arsenic levels in hair, blood, or urine. Compared with the group aged 18 - 39 years, the group aged 40 - 59 years and the group aged over 60 years showed significantly higher risks of arsenic poisoning-related skin lesions (adjusted OR = 11.34, 95% CI: 5.98, 21.50, P < 0.001; adjusted OR = 71.82, 95% CI: 35.81, 144.05, P < 0.001, respectively). Compared with the residents in the Wangyangqiao village, residents in the Heshan village and Huangchang village showed significantly higher risks of arsenic poisoning-related skin lesions (adjusted OR = 2.89, 95% CI: 2.05, 4.08, P < 0.001; adjusted OR = 4.13, 95% CI: 1.94, 8.78, P < 0.001, respectively). The risk of arsenic poisoning-related skin lesions was significantly higher in residents with occupational exposure history than in those without (adjusted OR = 1.99, 95% CI: 1.04, 3.83, P = 0.039) . Conclusion:Nearly 70% of the residents presented with arsenic poisoning-related skin lesions in an arsenic tailing area in Hunan Province, and the duration and previous degree of arsenic exposure were associated with the risk of arsenic poisoning-related skin lesions.

A preliminary study on the effect of arsenic exposure on necroptosis of mouse myocardial cells / 中华地方病学杂志

Objective:To study the effects of arsenic exposure on necroptosis pathway and inflammatory response of mouse myocardial cells.Methods:Sixty male C57BL/6J mice were randomly divided into control group (group C) and low, medium, and high dose arsenic exposure groups (groups L, M, H) based on body weight using a random number table method. Each group had 15 mice, and they drank 0.00, 0.15, 1.50, and 15.00 mg/L arsenic trioxide (As 2O 3) solution prepared with deionized water. The exposure period was 12 weeks. Hematoxylin-eosin (HE) staining and Masson trichrome staining of paraffin-embedded heart tissues were used to observe the histopathology changes of the heart. Transmission electron microscopy (TEM) was used to evaluate the ultrastructural changes of myocardial cells. The quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression of inflammatory genes [tumor necrosis factor (TNF)-α and interleukin(IL)-6] and the genes involved in necroptosis pathway [receptor-interacting protein (RIP) 1, RIP3 and mixed-lineage kinase domain-like protein (MLKL)]. Protein expressions of RIP1 and RIP3 in the heart were assessed by western blotting. Results:Histopathological examination results showed there were myocardial necrosis, inflammatory cells infiltration and fibroblasts hyperplasia and other changes in groups M and H. TEM analysis revealed marked ultrastructural changes in groups M and H, including fractured myofibril, fractured Z lines of sarcomere, and swollen mitochondria with fractured cristae. Compared with group C (1.00 ± 0.00), the mRNA expression of RIP1 in group H was significantly up-regulated (1.41 ± 0.06, P < 0.05); the mRNA expressions of RIP3 (1.29 ± 0.14, 1.56 ± 0.08), MLKL (1.23 ± 0.05, 1.36 ± 0.07), TNF-α (2.20 ± 0.10, 2.23 ± 0.18) and IL-6 (1.87 ± 0.16, 1.63 ± 0.15) were significantly up-regulated in groups M and H ( P < 0.05). The protein expressions of RIP1 (0.43 ± 0.04, 0.50 ± 0.04) and RIP3 (0.68 ± 0.02, 0.84 ± 0.05) in groups M and H were higher than those in group C (0.25 ± 0.01, 0.45 ± 0.04, P < 0.05). Conclusion:Subchronic arsenic exposure induces histopathological changes such as myocardial necrosis and fibrosis in mice, inducing necroptosis and inflammatory reactions in myocardial cells.

Investigation results of drinking-water-borne endemic arsenic poisoning in Henan Province in 2019 / 中华地方病学杂志

Objective:To learn about the progress of prevention and control of drinking-water-borne endemic arsenic poisoning in Henan Province, and provide scientific basis for achieving the goal of eliminating high arsenic hazards as scheduled.Methods:From July to August 2019, in accordance with the requirements of the National Monitoring Program for Drinking-water-borne Endemic Arsenic Poisoning, a general survey was carried out in 26 high-arsenic villages in 6 counties of Henan Province to investigate the water improvement situation and the operation of water improvement projects, and the arsenic content in drinking water of households was measured, meanwhile, the arsenic poisoning status of permanent residents in high-arsenic villages was investigated.Results:All 26 villages with high arsenic content in the province had undergone water improvement, with a water improvement rate of 100.00%. A total of 18 water improvement projects were investigated in 26 high-arsenic villages, all of which were operating normally. Twenty-six water samples were collected, and the arsenic content in the household water was < 0.01 mg/L, which met the sanitary standards for drinking water. No patient of endemic arsenic poisoning was found during the survey.Conclusion:In Henan Province, the drinking-water-borne endemic arsenic poisoning has been effectively controlled, and the prevention and control achievements should continue to be consolidated in the future.

Research progress on biomarkers of endemic arsenic poisoning / 中华地方病学杂志

The accumulation effect of arsenic and low arsenic exposure can cause sustained health damage to people in arsenic poisoning areas. Early diagnosis and prevention of arsenic poisoning have become the focus of current prevention and control, and biomarkers have important application value in early diagnosis and prevention of diseases. Therefore, the screening and application of sensitive and specific biomarkers of arsenic poisoning are of great significance for the continuous elimination of arsenic poisoning. In this paper, the research progress of biomarkers of endemic arsenic poisoning is reviewed, in order to provide reference for the continuous prevention and control, early monitoring and early warning of endemic arsenic poisoning.

Analysis of monitoring results of coal-burning-borne endemic arsenism in Shaanxi Province from 2015 to 2020 / 中华地方病学杂志

Objective:To learn about the changes of the condition of coal-burning-borne endemic arsenism, the use of improved stoves and the formation of health-related behaviors in Shaanxi Province, and evaluate the effect of prevention and control measures.Methods:From 2015 to 2020, according to the "Implementation Plan for Monitoring Coal-burning-borne Endemic Arsenism in Shaanxi Province", regular field surveys were carried out in 4 natural villages, 2 counties in Ankang City and Hanzhong City, Shaanxi Province, to learn about the basic prevention and control situation in the monitoring village. Using the simple random sampling method, 10 families in each village were selected to investigate the use of stoves and the formation of health-related behaviors, and 5 of these families were selected to collect coal samples for arsenic content determination in accordance with the "Determination of Arsenic in Coal" (GB/T 3058-2008). According to the "Diagnosis of Endemic Arsenicosis" (WS/T 211-2015), the condition of the people exposed to high arsenic coal in the monitoring village was investigated. Urine samples of 30 adult patients (half males and half females) with arsenic poisoning were collected, the content of arsenic in urine was determined by the "Urine-Determination of Arsenic-Silver Diethyldithiocarbamate-Triethanolamine-Spectrophotometric Method" (WS/T 28-1996).Results:A total of 240 households were monitored in the past 6 years, and the quality conformance and correct utilization rates of improved stoves in the households monitored in the disease areas remained at 100.00% in 2018 - 2020. The utilization rate of clean energy increased from 75.00% (30/40) in 2015 to 100.00% (40/40) in 2018 - 2020 (χ 2trend = 25.5, P < 0.001). The 73.75% (177/240) of households using a variety of clean energy. From 2018 to 2020, the correct drying, storage and pre-processing washing rates of corn and pepper continued to reach 100.00% (40/40). The arsenic content of coal ( n = 120) in the disease areas was (118.09 ± 57.91) mg/kg, ranging from 16.70 to 280.94 mg/kg. The detection rate of arsenic poisoning decreased from 6.34% (231/3 646) in 2015 to 2.90% (109/3 754) in 2020 (χ 2trend = 121.8, P < 0.001), and no skin cancer or Bowen's disease was detected. The geometric mean of arsenic content in urine ( n = 720) was 0.038 1 mg/L, ranging from 0.000 5 to 0.312 9 mg/L. Conclusions:The condition of coal-burning-borne endemic arsenism areas in Shaanxi Province has reached the national elimination standard. The quality and correct utilization rate of improved stoves and the rate of using clean energy have increased. The healthy-related behaviors the people in the endemic areas have been basically formed. The prevention and control work has achieved good results.

The role of Toll-like receptor 4-mediated immune inflammation in inorganic arsenic-induced liver fibrosis in rats / 中华地方病学杂志

Objective:To observe the expression levels of Toll-like receptor 4 (TLR4) signaling pathway-related proteins and their phosphorylation in the liver tissues of rats with inorganic arsenic poisoning, and to explore the role of TLR4-mediated inflammatory signaling pathway in arsenic-induced liver fibrosis injury.Methods:Eighteen healthy weanling SD rats were divided into 3 groups according to their body weight (80 - 100 g) using a random number table (6 rats in each group, half males and half females). The control group was given 10 ml/kg of normal saline by gavage. The sodium arsenite (NaAsO 2) exposure group was given 10 mg/kg of NaAsO 2 by gavage. The TAK-242 intervention group was given 10 mg/kg of NaAsO 2 by gavage, and 0.5 mg/kg of TAK-242 was also administered intraperitoneally to inhibit TLR4 after 12 weeks. All rats were administered 6 days a week for 36 weeks. At the end of the treatment, the liver tissues and serum of the rats in each group were collected. HE and Masson staining were used to observe the pathological and fibrotic changes of the liver tissues. Automatic biochemical analyzer was used to detect serum liver function indexes of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Western blot was used to detect the expression changes of rat liver fibrosis protein α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), Vimentin and TLR4 signaling pathway-related proteins TLR4, nuclear factor κB (NF-κB)-p65 subunit (p65), NF-κB-p50 subunit (p50) and their phosphorylation p-p65 and p-p50 expression levels. Enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion levels of inflammatory related factors interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-10. Results:HE and Masson staining results showed that compared with the control group, the NaAsO 2 exposure group showed significant inflammatory cell infiltration, hepatocyte necrosis and collagen fibrous deposition, while the TAK-242 intervention group showed improvement of the inflammatory cell infiltration and reduction of collagen fibrous deposition compared with the NaAsO 2 exposure group. The results of serum liver function indexes showed that ALT, AST and ALP in NaAsO 2 exposure group were increased compared with the control group, but the TAK-242 intervention group was significantly decreased compared with the NaAsO 2 exposure group ( P < 0.05). Western bolt results showed that in NaAsO 2 exposure group, the expression levels of fibrosis protein α-SMA, TGF-β1 and Vimentin (1.04 ± 0.19, 0.92 ± 0.14, 1.20 ± 0.21) and TLR4 signaling pathway-related proteins and their phosphorylation TLR4, p50, p-p50 and p-p65 (1.16 ± 0.21, 0.95 ± 0.16, 1.24 ± 0.23, 1.56 ± 0.25) were higher than the control group (0.44 ± 0.08, 0.42 ± 0.08, 0.72 ± 0.07, 0.69 ± 0.15, 0.71 ± 0.11, 0.46 ± 0.07, 0.54 ± 0.11, P < 0.05), and the TAK-242 intervention group (0.60 ± 0.13, 0.59 ± 0.16, 0.49 ± 0.11, 0.47 ± 0.08, 0.86 ± 0.09, 0.79 ± 0.14, 1.02 ± 0.17) were lower than the NaAsO 2 exposure group ( P < 0.05). There was no significant difference in the expression level of TLR4 signal pathway-related protein p65 among the three groups ( F = 14.29, P = 0.053). ELISA results showed that the secretion levels of IL-6 and TNF-α [(98.89 ± 4.58), (83.25 ± 4.57) ng/g] in rats liver tissues of the NaAsO 2 exposure group were higher than the control group [(27.30 ± 3.92), (27.77 ± 1.83) ng/g, P < 0.05], while the secretion level of IL-10 [(36.88 ± 3.86) ng/g] was lower than the control group [(77.96 ± 7.87) ng/g, P < 0.05]. In TAK-242 intervention group, IL-6 and TNF-α secretion levels [(44.32 ± 3.60), (36.51 ± 2.93) ng/g] were lower and IL-10 secretion level [(60.40 ± 4.94) ng/g] was higher compared with the NaAsO 2 exposure group ( P < 0.05). Conclusion:TLR4-mediated inflammatory signaling pathway-related proteins and their phosphorylation are highly expressed in the liver tissues of rats with inorganic arsenic poisoning, and inhibition of TLR4 signaling pathway could significantly reduce the degree of liver fibrosis injury caused by inorganic arsenic in rats.

The hypermethylation of FOXP3 gene as an epigenetic marker for the identification of arsenic poisoning risk.

Background and Purpose: Arsenic exposure can lead to skin lesions and multiple organ damage, which are not easily reversible and for which there is no effective therapeutics. Identification of reliable epigenetic markers is essential for early recognition of arsenic poisoning risk. Anomalous DNA methylation of immune homeostasis regulator FOXP3 is a critical mechanism for triggering arsenic poisoning. This study aims to explore the value of FOXP3 methylation in the identification of arsenic poisoning risk.Methods: 88 arsenic poisoning subjects and 41 references were recruited. Urinary arsenic contents and FOXP3 methylation in PBLCs was measured by ICP-MS and pyrosequencing, respectively.Results: The results showed that the elevated FOXP3 methylation in PBLCs were associated with the increased levels of urinary arsenic and were positively associated with the increased risk of arsenic poisoning and its progression. The result of mediation analysis revealed that 24.3% of the effect of arsenic exposure on the risk of arsenic poisoning was mediated by increased FOXP3 methylation. Additionally, we constructed a nomogram model with FOXP3 methylation as an epigenetic predictor to assess the probability of individual arsenic poisoning. The model showed a robust ability in the discrimination of arsenic poisoning risk, with an area under receiver operating characteristics curve of 0.897(0.845-0.949) and more than 70% accuracy. The calibration curves and the Harrell concordance index showed that the consistency rate between the probability predicted by the nomogram model and the actual probability is 89.7%.Conclusions: Taken together, we found the great potential of FOXP3 methylation for the identification of arsenic poisoning risk and provided a new approach to the application of epigenetic markers in accurately quantifying the risk of adverse outcomes.

Genome-wide DNA methylation pattern in whole blood of patients with coal-burning arsenic poisoning.

Exposure to coal-burning arsenic leads to an increased risk of cancer, multi-systems damage and chronic diseases, with DNA methylation one potential mechanism of arsenic toxicity. There are few studies on genome-wide methylation in the coal-burning arsenic poisoning population. Illumina 850 K methylation beadchip is the most suitable technology for DNA methylation of epigenome-wide association analysis. This study used 850 K to detect changes in Genome-wide DNA methylation in whole blood samples of 12 patients with coal-burning arsenic poisoning ( Arsenic poisoning group) and four healthy control participants (Healthy control group). There is clearly abnormal genome-wide DNA methylation in coal-burning arsenic poisoning, with 647 significantly different methylation positions, 524 different methylation regions and 335 significantly different methylation genes in arsenic poisoning patients compared with healthy controls. Further functional analysis of Gene ontology (GO) and Kyoto encyclopedia of genes (KEGG) found 592 GO items and 131 KEGG pathways between patients of coal-burning arsenic poisoning and healthy control. Then, analysis of gene degree and combined-score identified NAPRT1, NT5C3B, NEDD4L, SLC22A3 and RAB11B as target genes. Further validation by qRT-PCR indicates that mRNA expression of five genes changes significantly in the arsenic poisoning group (n = 72) compared to the healthy control group (n = 72). These results showed the genome-wide methylation pattern and highlighted five critical genes within the coal-burning arsenic poisoning population that involve Nicotinate and nicotinamide metabolism, Choline metabolism in cancer, and Ubiquitin mediated proteolysis. Next, the methylation profile of coal burning arsenic poisoning will be further excavation and the mechanism of coal burning arsenic poisoning will be further explored from five genes related pathways and functions.

El riesgo de los medicamentos naturales: un caso de exposición al arsénico / The risk of natural medicines: a case of arsenic exposure

El arsénico es un elemento químico del grupo de los metaloides o semimetales presente en el aire, en el agua y en la tierra en forma orgánica o inorgánica. La intoxicación por arsénico puede ser aguda (menos de 14 días de exposición), crónica o arsenicosis (por exposición más de 6 meses) y subcrónica. El ayurveda es un sistema de medicina tradicional india; sus medicinas se dividen en hierbas y rasa-shastra, combinación de hierbas, metales, minerales y gemas. Sus expertos mantienen que, preparadas y administradas apropiadamente, son seguras. Sin embargo, se han demostrado múltiples casos de intoxicación por metales pesados relacionados con su uso. Presentamos un caso clínico de exposición al arsénico secundario a la ingesta mantenida de medicamentos ayurvédicos (AU)

Arsenic is a chemical element that belongs to the group of metalloids or semi-metals, present in air, water and soil in organic or inorganic form. Arsenic poisoning can be acute (fewer than 14 days’ exposure), chronic (arsenicosis, more than 6 months) or subchronic. Ayurveda is a traditional medical system in which medicines are divided into herbal and rasashastra, combining herbs, metals, minerals and gems. Experts assert that they are safe when properly prepared and administered. However, multiple cases of heavy metal poisoning related to their use have been reported. We present a clinical case of subchronic arsenic poisoning secondary to sustained intake of ayurvedic medicine. (AU)

Nanoinspired Biocompatible Chemosensors: Progress toward Efficient Prognosis of Arsenic Poisoning.

Diagnosing heavy metals poisoning in human beings is of paramount importance. In this work, we present the design of a biocompatible FexNi(1-x)O hierarchical nanostructure-based sensor for ultraselective detection of arsenate (As(V)) ions in biological environments (e.g., body fluids, blood plasma, etc.). A novel iron doping technique was employed to fabricate the nanostructures rich with Fe cores to induce ultraselectivity toward arsenates. These nanostructures were used as dispersed markers and thin films deposited on Si/SiO2 substrates to support in vivo and in vitro detection of As(V) ions. The device demonstrated excellent sensitivity with a maximum response of 64.7% (for 1000 ppm As(V) ions) with a limit of detection of 1 ppb in blood plasma. The sensor's response time (τr) was 5 s with 95.48% recovery with a maximum error of ±0.549% after three washes. The device showed excellent response stability for 63 days with a maximum error of ±1.27%. The sensor devices were highly reproducible, with a maximum variation of ±0.6% in response for a batch of four devices. Due to Fe doping, the nanostructures in suspension demonstrated as arsenate markers with excellent cytocompatibility (with dosage up to 1 mg/mL) for human umbilical vein endothelial cells and 3T3 fibroblasts (LDH < 120 and cell viability ∼80%) till 48 h of incubation. The sensing mechanism suggested that the nanostructures not only detect arsenates but also prevent their substantial reduction to arsenites under anoxic environments. Thus, the sensors may show considerable progress toward early arsenate detection in living systems.