Cardiovascular Disease Burden Attributable to High Sodium Intake in China: A Longitudinal Study from 1990 to 2019.

BACKGROUND: Overconsumption of sodium has been identified as a key driving factor for diet-related cardiovascular diseases (CVDs). China, being a country bearing a hefty burden of CVD, has a large population with diverse cultural traditions and ethnic beliefs, which complicates the patterns of dietary sodium intake, necessitating a systematic investigation into the profile of the high sodium intake (HSI)-related burden of CVD within its subregions. This study aims to estimate the evolving patterns of HSI-induced CVD burden across China from 1990 to 2019. METHODS: The methodology used in the Global Burden of Disease Study was followed to assess deaths and disability-adjusted life years (DALYs) by age, sex, region, and socio-demographic index (SDI). The estimated annual percentage change (EAPC) was calculated to quantify the secular changes in the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR). RESULTS: In 2019, 0.79 million deaths and 1.93 million DALYs of CVD were attributed to HSI, an increase of 53.91% and 39.39% since 1990, respectively. Nevertheless, a downward trend in ASMR (EAPC: -1.45, 95% CI: -1.55, -1.35) and ASDR (EAPC: -1.61, 95% CI: -1.68, -1.53) was detected over time. ASMR and ASDR were higher for males, individuals aged ≥60 years, and regions with low-middle SDI. A markedly negative association between the EAPC in both ASMR and ASDR and the SDI was found in 2019 (ρ = -0.659, p < 0.001 and ρ = -0.558, p < 0.001, respectively). CONCLUSIONS: The HSI-induced CVD burden is gender-, age-, and socioeconomic-dependent. Integrated and targeted strategies for CVD prevention are anticipated in the future throughout China.

Establishing a nutrition calculation model for catering food according to the influencing factors of energy and nutrient content in food processing.

Objective: This study aimed to establish an accurate and efficient scientific calculation model for the nutritional composition of catering food to estimate energy and nutrient content of catering food. Methods: We constructed a scientific raw material classification database based on the Chinese food composition table by calculating the representative values of each food raw material type. Using China's common cooking methods, we cooked 150 dishes including grains, meat, poultry, fish, eggs, and vegetables and established a database showing the raw and cooked ratios of various food materials by calculating the ratio of raw to cooked and the China Total Diet Research database. The effects of various cooking methods on the nutritional composition of catering food were analyzed to determine correction factors for such methods on the nutritional components. Finally, we linked the raw material classification, raw and cooked ratio, and nutritional component correction factor databases to establish a model for calculating the nutritional components of catering food. The model was verified with nine representative Chinese dishes. Results: We have completed the construction of an accurate and efficient scientific calculation model for the nutritional composition of catering food, which improves the accuracy of nutrition composition calculation. Conclusion: The model constructed in this study was scientific, accurate, and efficient, thereby promising in facilitating the accurate calculation and correct labeling of nutritional components in catering food.

Dosage-effect of selenium supplementation on blood glucose and oxidative stress in type 2 diabetes mellitus and normal mice.

BACKGROUND: The effectiveness of selenium (Se) supplementation on glycemic control is disparate. OBJECTIVE: This study aims to evaluate the effects of different dosages of Se diets on the blood glucose in type 2 diabetes mellitus (T2DM, db/db) and normal (db/m) mice. METHODS: The db/db and db/m mice were fed with different dosages of Se supplemented diets (0, 0.1, 0.3, 0.9, 2.7 mg/kg) for 12 weeks, respectively. Se concentrations of tissues, physical and biochemical characteristics, oxidative stress indexes and gene expression related to glucose, lipid metabolism and Se transporters of liver were detected. RESULTS: The Se concentrations in tissues were related to the dosages of Se supplementation in db/db (blood: slope=11.69, r = 0.924; skeletal muscle: slope=0.36, r = 0.505; liver: slope=22.12, r = 0.828; kidney: slope=11.81, r = 0.736) and db/m mice (blood: slope=19.89, r = 0.876; skeletal muscle: slope=2.80, r = 0.883; liver: slope=44.75, r = 0.717; kidney: slope=60.15, r = 0.960). Compared with Se2.7 group, the fasting blood glucose (FBG) levels of Se0.1 and Se0.3 group were decreased at week3 in db/db mice. Compared with control (Se0) group, the FBG levels of Se2.7 group were increased from week6 to week12 in db/m mice. The oral glucose tolerance test (OGTT) showed that the area under the curve (AUC) of Se0.3 group was lower than that of Se0.9 and Se2.7 group in db/m mice. Furthermore, compared with control group, the malondialdehyde (MDA) level in skeletal muscle of Se0.1 group was decreased, while that of Se2.7 group was increased in db/db mice; the glutathione peroxidase (GPx) activity in skeletal muscle of Se0.3, Se0.9 and Se2.7 group was increased both in db/db and db/m mice. For db/db mice, glucose-6-phosphatase catalytic (G6pc) expression of other groups were lower and fatty acid synthase (Fasn) expression of Se0.9 group were lower compared with Se0.3 group. For db/m mice, compared with Se0.3 group, (peroxisome proliferative activated receptor gamma coactivator 1 alpha) Pgc-1α expression of control and Se0.9 group were higher; (phosphoenolpyruvate carboxykinase 1) Pck1 expression of Se0.1, Se0.9, and Se2.7 group were higher. CONCLUSION: Low dosages (0.1 and 0.3 mg/kg) of Se supplementation exerted beneficial effects on FBG levels and glucose tolerance through regulating hepatic glycolysis and gluconeogenesis and inhibit the oxidative stress while high dosages of Se (0.9 and 2.7 mg/kg) supplementation enhanced FBG levels, impaired glucose tolerance and aggravate oxidative stress.

The Burden of Gastric Cancer Attributable to High Sodium Intake: A Longitudinal Study from 1990 to 2019 in China.

BACKGROUNDS: Excessive intake of sodium is a crucial risk factor of gastric cancer. However, it is still unclear whether the profile of gastric cancer burden is attributable to high sodium intake in China. This study aims to evaluate the levels and trends of gastric cancer burden attributable to high sodium intake across China from 1990 to 2019. METHODS: We acquired data from the GBD (Global Burden of Disease Study) 2019 via the Global Health Data Exchange query tool. The details of regions from 1 January 1990 to 31 December 2019 from the China National Center for Food Safety Risk Assessment were also used. We conducted an integrated analysis on the gastric cancer burden attributable to high sodium intake among Chinese residents. The gastric cancer-related deaths, disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR), all being calculated to be attributable to sodium intake, were reckoned as separated by age, sex, SDI, and regions. Then, the estimated annual percentage change (EAPC) was regarded as the secular trends of gastric cancer's ASMR and ASDR due to high sodium intake from 1990 to 2019. We further explored the associations between SDI (Socio-demographic index) and the ASMR and ASDR. The rates were calculated per 100,000 population as age-standardized rates. RESULTS: Briefly, the number of gastric cancer-related deaths and DALYs being attributed to high sodium intake were 37,131.48 (95% UI: 833.14 to 138,478.72) and 873,813.19 (95% UI: 19,283.13 to 3,220,231.82) in 2019; both have increased by a third since 1990. However, the ASMR decreased with an EAPC of -1.72% (95% CI: -2.11% to -1.33%), while ASDR increased with an EAPC of 0.36% (95% CI: 0.08% to 0.68%), respectively. The age-specific numbers and rates of deaths, as well as DALYs of gastric cancer being attributed to high sodium intake, elevated gradually with age. And, they were higher in males than in females. The gastric cancer burden being attributed to high sodium intake in 2019 and its temporal trends from 1990 to 2019 varied greatly by SDI quintile and geographic locations. There was a strong negative association between the EAPC in ASMR and SDI in 2019 (ρ = -0.642, p < 0.001). The EAPC in ASDR and SDI also exhibited a negative connection in 2019 (ρ = -0.538, p = 0.0012). CONCLUSIONS: Overall, using a longitudinal sample from different regions, the study presented that gastric cancer burden attributed to high sodium intake still exists seriously and varies remarkably by regions, sex, and age across China. The disparity of socioeconomic status on disease burden also exists. Integrated and precise approaches for gastric cancer prevention are anticipated in the future.

Deep neural network for prediction of diet quality among doctors and nurses in North China during the COVID-19 pandemic.

Objective: The COVID-19 pandemic has placed unprecedented pressure on front-line healthcare workers, leading to poor health status, especially diet quality. This study aimed to develop a diet quality prediction model and determine the predictive effects of personality traits, socioeconomic status, lifestyles, and individual and working conditions on diet quality among doctors and nurses during the COVID-19 pandemic. Methods: A total of 5,013 doctors and nurses from thirty-nine COVID-19 designated hospitals provided valid responses in north China in 2022. Participants' data related to social-demographic characteristics, lifestyles, sleep quality, personality traits, burnout, work-related conflicts, and diet quality were collected with questionnaires. Deep Neural Network (DNN) was applied to develop a diet quality prediction model among doctors and nurses during the COVID-19 pandemic. Results: The mean score of diet quality was 46.14 ± 15.08; specifically, the mean scores for variety, adequacy, moderation, and overall balance were 14.33 ± 3.65, 17.99 ± 5.73, 9.41 ± 7.33, and 4.41 ± 2.98, respectively. The current study developed a DNN model with a 21-30-28-1 network framework for diet quality prediction. The DNN model achieved high prediction efficacy, and values of R2, MAE, MSE, and RMSE were 0.928, 0.048, 0.004, and 0.065, respectively. Among doctors and nurses in north China, the top five predictors in the diet quality prediction model were BMI, poor sleep quality, work-family conflict, negative emotional eating, and nutrition knowledge. Conclusion: During the COVID-19 pandemic, poor diet quality is prevalent among doctors and nurses in north China. Machine learning models can provide an automated identification mechanism for the prediction of diet quality. This study suggests that integrated interventions can be a promising approach to improving diet quality among doctors and nurses, particularly weight management, sleep quality improvement, work-family balance, decreased emotional eating, and increased nutrition knowledge.

Machine-learning prediction of BMI change among doctors and nurses in North China during the COVID-19 pandemic.

Objective: The COVID-19 pandemic has become a major public health concern over the past 3 years, leading to adverse effects on front-line healthcare workers. This study aimed to develop a Body Mass Index (BMI) change prediction model among doctors and nurses in North China during the COVID-19 pandemic, and further identified the predicting effects of lifestyles, sleep quality, work-related conditions, and personality traits on BMI change. Methods: The present study was a cross-sectional study conducted in North China, during May-August 2022. A total of 5,400 doctors and nurses were randomly recruited from 39 COVID-19 designated hospitals and 5,271 participants provided valid responses. Participants' data related to social-demographics, dietary behavior, lifestyle, sleep, personality, and work-related conflicts were collected with questionnaires. Deep Neural Network (DNN) was applied to develop a BMI change prediction model among doctors and nurses during the COVID-19 pandemic. Results: Of participants, only 2,216 (42.0%) individuals kept a stable BMI. Results showed that personality traits, dietary behaviors, lifestyles, sleep quality, burnout, and work-related conditions had effects on the BMI change among doctors and nurses. The prediction model for BMI change was developed with a 33-26-20-1 network framework. The DNN model achieved high prediction efficacy, and values of R 2, MAE, MSE, and RMSE for the model were 0.940, 0.027, 0.002, and 0.038, respectively. Among doctors and nurses, the top five predictors in the BMI change prediction model were unbalanced nutritional diet, poor sleep quality, work-family conflict, lack of exercise, and soft drinks consumption. Conclusion: During the COVID-19 pandemic, BMI change was highly prevalent among doctors and nurses in North China. Machine learning models can provide an automated identification mechanism for the prediction of BMI change. Personality traits, dietary behaviors, lifestyles, sleep quality, burnout, and work-related conditions have contributed to the BMI change prediction. Integrated treatment measures should be taken in the management of weight and BMI by policymakers, hospital administrators, and healthcare workers.

A preliminary cumulative risk assessment of Diethylhexyl phthalate and Dibutyl phthalate based on the inhibition of embryonic development via the PPARγ pathway.

BACKGROUND: Diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP) are the two most widely used plasticizers (PAEs) that may act as endocrine disruptors and cause developmental toxicity. METHODS: We measured intrauterine exposure to DEHP and DBP which are the two most widely used phthalates (PAEs) in the cord blood of 50 postpartum women using ultra-HPLC-tandem mass spectrometry and solid-phase extraction. The embryotoxicity of DEHP and DBP was evaluated using the human embryonic stem cell test (hEST). Based on the intrauterine exposure concentration of DEHP and DBP in pregnant women and the reference point of toxic effects in hEST, we used the reference point index (RPI) method to assess the cumulative risk of DBP and DEHP. RESULTS: The mean concentrations of DEHP and DBP were 99.9 µg/L and 24.7 µg/L, respectively. DEHP and DBP were weakly embryotoxic, and the benchmark dose lower confidence intervals were 29.99 and 0.99 µg/mL, respectively, as determined using hEST. Both DEHP and DBP inhibited embryonic development via PPAR/PTEN/Akt signal pathway. CONCLUSION: The findings suggest that the cumulative risk in pregnant women with a high level of exposure should receive more attention in the future.

Risk-Benefit Assessment of Consumption of Rice for Adult Men in China.

Objective: To evaluate the health impact of current and alternative patterns of rice consumption in Chinese adult men (40-79 years of age). Methods: We applied a risk-benefit assessment (RBA) model that took into account the health effects of selenium (Se), cadmium (Cd), and inorganic arsenic (i-As). The health effects included the prevention of prostate cancer associated with exposure to Se, and an increased risk of lung, bladder, and skin cancer for i-As and chronic kidney disease (CKD) for Cd. We defined the baseline scenario (BS) as the current individual mean daily consumption of rice in the population of interest and two alternative scenarios (AS): AS1 = 50 g/day and AS2 = 200 g/day. We estimated the health impact for different age groups in terms of change in Disability-Adjusted Life Years (ΔDALY). Results: The BS of rice consumption was 71.5-105.4 g/day in different age groups of adult men in China. We estimated that for AS1, the mean ΔDALY was -2.76 to 46.2/100,000 adult men of 40-79 years old. For AS2, the mean ΔDALY was 41.3 to 130.8/100,000 individuals in this population group. Conclusion: Our results showed that, based on associated exposure to selenium, cadmium, and i-As in rice, the current consumption of rice does not pose a risk to adult men in China. Also, a lower (50 g/day) or higher (200 g/day) rice consumption will not bring larger beneficial effects.

Association Between Selenium Level in Blood and Glycolipid Metabolism in Residents of Enshi Prefecture, China.

The present study aimed to detect selenium (Se) levels in the blood of Enshi Prefecture residents in China and investigate the relationship between blood Se levels and glucose or lipid metabolism disorder. A cross-sectional study was conducted, and 1876 subjects were selected through cluster random sampling from Enshi Prefecture using a questionnaire survey, physical examinations, and biochemical blood tests. The mean blood Se level in the overall population was 0.128 ± 0.178 µg/mL. Se exhibits a "U"-shaped curve on the serum fasting plasma glucose (FPG) of the total samples, that is, when the blood Se is more than 0.131 µg/mL or less than 0.062 µg/mL, the FPG increases significantly. A significant negative correlation was demonstrated between the FPG levels of the 4-17-year-old age group and different blood Se levels (P < 0.001). No significant correlation was demonstrated between the serum triglyceride (TG) and blood Se levels. However, a positive correlation was demonstrated between blood Se and serum total cholesterol (TC) levels and the incidence of high cholesterol in the total population (P < 0.001). The odds ratio and related 95% confidence interval for the incidence of high cholesterol between the highest (≥ 0.133 µg/mL) and lowest blood Se (< 0.064 µg/mL) levels was 2.64 and 1.48-4.79, respectively. The results of this study are very important for the safety scope and risk-benefit assessment of Se in the human; however, further investigation with a larger sample size is required.

A case report of acute renal failure caused by Amanita neoovoidea poisoning in Anhui Province, eastern China.

Amanita neoovoidea (genus Amanita Pers.) poisoning leads to acute renal failure. Here, we present seven case reports of acute renal failure with acute hepatic failure due to ingestion of A. neoovoidea. Clinical manifestations included gastrointestinal symptoms 1-72 h after ingestion; elevation of renal parameters and blood uric acid, blood urea nitrogen, and creatinine levels; a few abnormal hepatic parameters, primarily albumin decrease and alanine aminotransferase increase; and elevation of zymogram parameters such as cholinesterase and lactate dehydrogenase. To determine whether the hepatic/renal lesions were caused by amanitins, we analyzed the blood and urine samples of patients and specimens of poisonous mushrooms. Morphological and molecular biological analyses indicated that the mushroom was A. neoovoidea. However, no amatoxins and phallotoxins were detected in its basidiomata.

Di-(2-ethylhexyl)-phthalate induces apoptosis via the PPARγ/PTEN/AKT pathway in differentiated human embryonic stem cells.

[OBJECTIVE]: Di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, may act as an endocrine disruptor and cause developmental toxicity. Differentiated human embryonic stem cells (hESCs) were used to investigate the underlying mechanism of the embryotoxicity induced by DEHP. [Materials and Methods] H9-hESCs were treated with DEHP at different concentrations for 10 days, and the cytotoxicity of DEHP on cell proliferation was determined using a cell-microelectronic sensing technique (Real-Time Cellular Analysis: RTCA). Based on the 50% inhibitory proliferation concentration (IC50), differentiated H9-hESCs were treated with DEHP at 0, 50, 100, and 200 µg/ml for 120 h, followed by measurement of its toxic effects on the transcriptome by mRNA microarray and QuantiGene Plex (QGP). Proteins were detected by the iTRAQ-based proteomics method and the proteins related to the PPARγ/PTEN/Akt pathways were measured by western blotting. The progression of the cell cycle and apoptosis were characterized using flow cytometry (FCM). In other experiments, hESCs were pre-treated with GW9662 (20 µM), a specific PPARγ inhibitor, for 30 min, followed by exposure to GW9662 (20 µM) and DEHP (200 µg/ml) for 120 h to observe the underlying mechanism of DEHP's embryotoxicity. [RESULTS]: DEHP inhibited H9-hESC cell proliferation in a dose-dependent manner, with an IC50 of 165.78 µg/ml. FCM results showed that DEHP could markedly induce cell cycle arrest and increase apoptosis. Gene microarray and QPG array analyses indicated that the peroxisome proliferator-activated receptor γ (PPARγ) was an apparent target for DEHP. We further demonstrated that DEHP could activate the PPARγ and upregulate the expression of PTEN downstream genes, and then play a negative role in the AKT signaling pathway. Cells pretreated with PPARγ inhibitor, GW9662, were shown to restore the effect of DEHP on the PPARγ/PTEN/AKT signaling pathway, and induce the recovery of cell cycle arrest and apoptosis. [CONCLUSION]: DEHP inhibited cell proliferation, promoted cell cycle arrest, and induced apoptosis through the PPARγ/PTEN/AKT signaling pathway in differentiated human embryonic stem cells. It suggested that DEHP exposure possibly cause reproductive or developmental toxicity in humans through the PPARγ signaling pathway.

Zearalenone causes embryotoxicity and induces oxidative stress and apoptosis in differentiated human embryonic stem cells.

In this study, murine embryonic stem cell test (mEST) and human embryonic stem cell test (hEST) models were developed to evaluate the embryonic toxicity of Zearalenone (ZEN) according to the methods established in our laboratory. The embryotoxicity of ZEN was described by comparing the three functions calculated based on three endpoints, that is, 50% inhibitory proliferation concentration (IC50) of embryonic stem cells (ESCs) and 3T3 cells and 50% inhibition of cardiomyocyte differentiation (ID50) of ESCs determined in the EST model. Moreover, differentiation of human embryonic stem cell (hESC) was initiated by embryoid bodies (EBs) formation; EBs were exposed to different concentrations of ZEN for 24 h to detect cellular reactive oxygen species (ROS) generation, the mitochondrial transmembrane potential (MMP), apoptosis, cell cycle, and the related protein expression. Based on the results of the three endpoints and functions of ZEN in mEST and hEST, ZEN was evaluated to have strong embryonic toxicity both by two models. The increases in cellular ROS and loss of MMP were observed at 2 and 4 µg/ml concentrations. Flow cytometry showed that ZEN induced cell cycle arrest and apoptosis. The upregulation of p53, caspase-9, caspase-3, and the ratio of Bax/Bcl-2 were observed at 2 and 4 µg/ml concentrations. Collectively these results demonstrate that ZEN has strong embryonic toxicity and induces oxidative stress and apoptosis in differentiated human ESCs.

Subchronic toxicity study of yttrium nitrate by 90-day repeated oral exposure in rats.

Concerns regarding the adverse effects of long-term exposure to low levels of rare earth elements (REEs) from foods on human health have arisen in recent years. Nevertheless, no official acceptable daily intake (ADI) has yet been proposed for either total REEs or individual REE. In accordance with the Organization for Economic Co-operation and Development (OECD) testing guideline, the present study was undertaken to evaluate the subchronic toxicity of yttrium, a representative heavy REE with higher contaminated level in foods in China, to achieve a no observed adverse effect level (NOAEL) which is a critical basis for the establishment of an ADI. Yttrium nitrate was orally administered to rats at doses of 0, 10, 30 and 90 mg/kg/day for 90 days followed by a recovery period of 4 weeks. The following toxicity indices were measured: mortality, clinical signs, daily food consumption and weekly body weight; urinalysis, hematology, blood coagulation, clinical biochemistry and histopathology at the end of administration and recovery periods. No toxicologically significant changes were found in any yttrium-treated group as compared to the concurrent control group. Under the present experimental condition, the NOAEL in rats was thus set at 90 mg/kg for yttrium nitrate, i.e. 29.1 mg/kg for yttrium.

Persistence of Bowl Water Contamination during Sequential Flushes of Contaminated Toilets.

Toilets contaminated with infectious organisms are a recognized contact disease transmission hazard. Previous studies indicate that toilet bowl water can remain contaminated for several flushes after the contamination occurs. This study characterized contamination persistence over an extended series of flushes using both indicator particles and viable bacteria. For this study, toilets were seeded with microbe-size microbial surrogates and with Pseudomonas fluorescens or Clostridium difficile bacteria and flushed up to 24 times. Bowl water samples collected after seeding and after each flush indicated the clearance per flush and residual bowl water contaminant concentration. Toilets exhibited 3 + log10 contaminant reductions with the first flush, only 1-2 logs with the second flush, and less than 1 log thereafter. Contamination still was present 24 flushes post contamination. Clearance was modeled accurately by a two-stage exponential decay process. This study shows that toilet bowl water will remain contaminated many flushes after initial contamination, posing a risk of recurring environmental contamination and associated infection incidence.

Establishment and optimization of NMR-based cell metabonomics study protocols for neonatal Sprague-Dawley rat cardiomyocytes.

A quenching, harvesting, and extraction protocol was optimized for cardiomyocytes NMR metabonomics analysis in this study. Trypsin treatment and direct scraping cells in acetonitrile were compared for sample harvesting. The results showed trypsin treatment cause normalized concentration increasing of phosphocholine and metabolites leakage, since the trypsin-induced membrane broken and long term harvesting procedures. Then the intracellular metabolite extraction efficiency of methanol and acetonitrile were compared. As a result, washing twice with phosphate buffer, direct scraping cells and extracting with acetonitrile were chosen to prepare cardiomyocytes extracts samples for metabonomics studies. This optimized protocol is rapid, effective, and exhibits greater metabolite retention.

T-2 toxin inhibits murine ES cells cardiac differentiation and mitochondrial biogenesis by ROS and p-38 MAPK-mediated pathway.

OBJECTIVE: To investigate the effect of T-2 toxin on murine embryonic stem cells (ESCs) cardiac differentiation and mitochondrial biogenesis in vitro. METHODS: Cardiac differentiation of the mouse ESCs was initiated by embryoid bodies (EBs) formation in hanging drops. EBs were exposed to 0.5ng/ml T-2 toxin for 24, 72 and 120h. Cultures were observed daily for the appearance of contracting clusters, and cardiac-specific protein (α-actiniin) were measured by Western blot and immunocytochemistry. Mitochondrial ultrastructure was observed by confocal laser scanning microscopy and transmission EM photography. Reactive oxygen species (ROS) was monitored by H2-dichlorofluorescein-diacetate (H2DCF-DA). The phosphorylation of the p38 (p-p38) and p38 mitogen-activated protein kinase (MAPK) and the expression of mitochondrial biogenesis proteins, including peroxisome proliferator activated receptor coactivator-1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (mtTFA), and mitochondrial respiratory chain complex IV (COXIV) were analyzed using Western blot. In some experiments, mESCs were pre-treated with the antioxidant Trolox (200µM) for 30min, then exposed to Trolox (200µM) and T-2 toxin (0.5ng/ml) for 72h. RESULTS: Contracting clusters were observed under the microscope light and cardiac-specific protein (α-actinin) expressed positively indicated mESCs directly differentiated in cardiomyocytes. However, the cardiac differentiation was inhibited by T-2 toxin treatment 72 and 120h. ROS accumulated in murine ES cells in a time-dependent manner. The expression of p-p38 significantly increased in 24h group and decrease in 72 and 120h groups. The decrease of mitochondrial number and the mitochondrial biogenesis-related proteins expression, including PGC-1α, NRF-1, mtTFA, and COXIV decreased in a time-dependent manner with T-2 toxin treatment. However, the inhibition of mitochondrial biogenesis by T-2 toxin in differentiated mESCs was recovered significantly in the presence of the antioxidant Trolox. CONCLUSION: Taken together, T-2 toxin decreased the expression of PGC-1α, NRF-1, and mtTFA, inhibited mitochondrial biogenesis, and then inhibited the cardiac differentiation of murine ES cells, and the effect was partly responsible for the p38 MAPK mediated by ROS.

[Development of human embryonic stem cell platforms for human health-safety evaluation].

The human embryonic stem cells (hESCs) serve as a self-renewable, genetically-healthy, pluripotent and single source of all body cells, tissues and organs. Therefore, it is considered as the good standard for all human stem cells by US, Europe and international authorities. In this study, the standard and healthy human mesenchymal progenitors, ligament tissues, cardiomyocytes, keratinocytes, primary neurons, fibroblasts, and salivary serous cells were differentiated from hESCs. The human cellular health-safety of NaF, retinoic acid, 5-fluorouracil, dexamethasone, penicillin G, adriamycin, lead acetate PbAc, bisphenol A-biglycidyl methacrylate (Bis-GMA) were evaluated selectively on the standardized platforms of hESCs, hESCs-derived cardiomyocytes, keratinocytes, primary neurons, and fibroblasts. The evaluations were compared with those on the currently most adopted cellular platforms. Particularly, the sensitivity difference of PM2.5 toxicity on standardized and healthy hESCs derived fibroblasts, currently adopted immortalized human bronchial epithelial cells Beas-2B and human umbilical vein endothelial cells (HUVECs) were evaluated. The RESULTS showed that the standardized hESCs cellular platforms provided more sensitivity and accuracy for human cellular health-safety evaluation.

JAK2/STAT3 Pathway Mediates Protection of Metallothionein Against Doxorubicin-Induced Cytotoxicity in Mouse Cardiomyocytes.

Doxorubicin (Dox) is one of the most important anticancer agents; however, its clinical application is limited by its severe cardiotoxicity. In our previous study, we found that the gene expression levels of the Janus-activated kinase/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway were different between MT(-/-) cardiomyocytes and MT(+/+) cardiomyocytes when they were treated with Dox. Thus, this study was intended to investigate the role of JAK2/STAT3 pathway in metallothionein (MT) protection of Dox-induced cardiotoxicity. Tyrphostin AG490 (α-cyano-(3,4-dihydroxy)-N-benzylcinnamide) is a synthetic protein tyrosine kinase inhibitor which at first has been considered as a specific JAK2 inhibitor and can inhibit the JAK2/STAT3 signaling pathway. In the present study, AG490 was used to assess the role of JAK2/STAT3 in MT protection against Dox-induced cardiotoxicity. The AG490 can attenuate the MT protection by increasing lactate dehydrogenase and the number of apoptotic cells. Interestingly, pretreated with AG490, MT(-/-) cardiomyocytes were more sensitive than MT(+/+) to Dox-induced cytotoxicity as measured by reactive oxygen species generation, lipid peroxidation, and protein carbonylation. Metallothionein 1 and MT-2 messenger RNA were upregulated by Dox, and AG490 decreased the protein expression of MT-1 and MT-2. After Dox treatment, the protein expression of p-Jak2 and p-Stat3 levels was significantly increased in MT(+/+) cardiomyocytes, suggesting that the JAK2/STAT3 pathway was partially involved in MT protection against Dox-induced cardiotoxicity.