Toxicogenomics (TGx) refers to a set of technologies that assess genome-wide responses after toxic agent exposure. Altered gene expression patterns that are caused by specific exposures reveal how toxicants may disrupt cellular processes and lead to side effects. Development and application of " omics" technology facilitate the toxicogenomic research which sharing and interpretation of the enormous amount of biological information generated in toxicologic field. In recent years TGx has been widely valued and successfully applied as an effective research tool to evaluate the toxic effects of traditional Chinese medicine (TCM). Here we reviewed current progress in the field of TGx and focused on its application in traditional Chinese medicine safety evaluation, especially in revealing the mechanism, finding potential toxic biomarkers and studying compatibility detoxification of TCM.
Medicine, Chinese Traditional ; adverse effects ; Safety ; Toxicogenetics

Objective To investigate the status of the disease of the fluorosis and arsenism caused by coal-burning in Ankang city of Shaanxi. Methods Nine survey spots were chosen to carry out the epidemiological investigation of adult skeletal fluorosis and arsenism in the coal-polluted areas of Ankang, respectively using Determination of Fluorine in Coal (GB/T 4633-1997) to determine the coal fluorine and using hydride generation atomic fluorescence spectrophotometry(HCAFS) to determine coal arsenic. The diagnose of the adult skeletal fluorosis followed the Diagnosis of Clinical Classification for Endemic Skeletal Fluorosis Standard(GB 16396-1996), that of arsenism using Standard of Diagnosis for Endemic Arsensim (WS/T 211-2001). Results Totally 569 adults were investigated over the age of 16, among which 121 cases were skeletal fluorosis, with a total detection rate of 21.27%. Four cases of II degree and higher skeletal fluorosis patients were identified, accounting for 0.70% of the number of subjects. One hundred and thirty-two cases of arsenic poisonin were detected, in a rate of 23.20%. Ninety-five patients were identified with moderate or severe arsenic poisoning, accounting for 16.69% of subjects. A positive correlation was found between the detection rates of the skeletal fluorosis and the arsenism(r = 0.816, P < 0.01), as well as between the detection rate of skeletal fluorosis and fluoride content of coal(r = 0.775, P < 0.05). The detection rate of arsenism and arsenic content of coal also had close relationship (r = 0.761, P < 0.05). The detection rate of skeletal fluorosis in the group aged 40 - ,50 - , and 60 - [27.20%(34/125) ,29.27%(36/123), 28.13%(36/128)] was increased, compared the group of less than 40 years age[7.77%( 15/193), X~2 = 21.969,25.648,23.856,P<0.01].For the detection rate of arsenism,male[33.67%(99/294)]was obviously higher than female[12.00%(33/275),)(X~2=37.162,P<0.01].Conclusions A high detection rate of fhorosis is correlated with arsenic poisoning,but the probability of the two diseases simultaneously occurred in a person is not high.In this polluted area.when fluoride accumulates to a certain level as in aduh,the detection rates no longer varies obviously;however,that of arsenism increases along with the age.

Objective To know the condition and feature of water-born endemic arsenism in Shaanxi province, and to provide scientific evidences for prevention and treatment of the disease. Methods In 2009, 8 villages of Duhe, Miaogou, Sanhe, Caiyuan in Shanyang county and Shuanglong, Guangming, Donghekou in Zhen'an county and Guojiawan in Mian county as monitoring sites from both the found water-born arsenic poisoning areas and potential ones of drinking water arsenic ＞ 0.15 mg/L were selected. The disease conditions of residents who lived for more than six months of continuous residence, were investigated according to "Endemic Arsenism Diagnostic Criteria" (WS/T 211-2001 ) and arsenic level in the drinking water were determined. Results Seven thousand six hundred and ninety-three individuals were investigated and 612 cases of arsenism were diagnosed in the 8 villages, the prevalence rate was 7.96%(612/7693). Mild patients accounted for 33.17%(203/612), moderate patients accounted for 50.16%(307/612), and severe patients accounted for 16.67%(102/612). The detection rate for male was 9.99%(408/4085), for female was 5.65%(204/3608), the former was higher than the latter(x2 = 49.138,P ＜ 0.01 ). The older the age was, the higher the rate was(x2 = 770.708, P ＜ 0.01 ). Main clinical manifestation of the patients was depigmentation and pigmentation in skin. Patients with one symptom accounted for 43.30% (265/612), with two symptoms accounted for 56.70% (347/612). Three hundred and seventy drinking water samples were detected, the median of arsenism content was 0.005 mg/L, ranged 0 - 1.660 mg/L. The over-limit rate of arsenic level in the drinking water were 11.62% (43/370). Conclusion Water-born endemic arsenism is mildly prevailing in Shaanxi province, however, great attention should be given to control and monitoring of the disease.

Objective To analyze the epidemiologic characteristics of epidemic hemorrhagic fever syndrome (EHF) from 2004 to 2010 and provide scientific basis for formulating control measures.Methods Epidemiological data of EHF between 2004 to 2010 were obtained from the“National Disease Surveillance Report on Management Information System”,and the population data were from the“National Disease Surveillance Information Management System for Basic Information Report System”.Descriptive epidemiological methods was used for statistical analysis.ResultsA total of 173 cases were reported in Qian'an from 2004 to 2010.From 2004 to 2010,the cases were 86,67,12,1,0,1,and 7 cases,respectively,and the rate were 13.12/10 million ( 86/640 249 ),10.42/10 million (67/642 688 ),1.86/10 million ( 12/645 124),0.15/10 million (1/647 983 ),0(0/650 720),0.15/10 million( 1/653 839),and 0.11/10 million(7/657 380),respectively.The overall rate was 3.86/10 million(25/648 283) of population.From 2004 to 2008 the incidence reported declined rapidly,then increased slowly after 2009.The cases were found intensively in winter(November - next January) and spring season (february - may).The incidence in the age group of 10 - 45 was higher than that of other age groups,and the total number of cases was 82.08％(142/173).The incidence in males( 114 cases) was higher than that of females(59 cases).Occupational distribution mainly to peasants and students,which accounted for 87.86％ (152/173).Conclusions Epidemic in the city declines rapidly follows by a slow recovery,suggesting that in the future surveillance,mice-killing and protection of vulnerable population should be strengthened.

Objective To analyze the outcome of the epidemiological investigation on an animal plague in Dingbian County of Shaanxi Province.Methods The region of 25 square kiolmeters(km2)in Hongliugou Town was selected as monitoring point of plague to investigate on host animals,etiology and serology.The epidemic area was classified,deratization and depulization were correspondingly adopted.Health education was carried out for prevention knowledge of plague,and questionnaire survey was conducted among residents and medical staff in the epidemic area.Result The average rat density in monitoring site was 8.38 rats per hectare in Hongliugou Town.Average rate infected with flea and flea index were 50.4%(56/111)and 1.81,respectively.The epidemic area was classified 3 types,and came up to the demand after corresponding measures adopted.In the epidemic area,the pass rate of the prevention and control knowledge were 62.00%(31/50)in residents and 92.98%(53/57) in medical staff.Conclusions Plague epizootic can be discovered by exercising regular monitoring and controlledimmed iately and effectively by taking the appropriate control measures.

Objective To investigate the current situation of endemic fluorosis associated with drinking water in Shaanxi province in 2008, providing prevention and control work with scientific evidence. Methods According to data of drinking water endemic fluorosis in Shaanxi, 15 counties in Yulin, Weinan and Xianyang city were divided into mild, moderate and severe diseased areas according to fuoride level in the drinking water or the fluorosis severity, and 12,39,45 endemic fluorosis villages were selected respectively from each area. Dental fluorosis for all the children aged 8 - 12 years old and clinical skeletal fluorosis for the people over the age of 16 were examined. In mild, moderate and severe areas, 30% of the survey villages received X-ray to examine skeletal fuorosis. Five water samples were collected from villages with unimproved water respectively from the east, the west, the south, the north, the middle; if there was less than 5 that could be sampled, then all were collected, moreover 3 peripheral and 1 central water samples were collected from villages with improved water. Also in mild, moderate and severe illness areas, 50% of the surveyed villages were selected; in each village, 30 urine samples of the children aged 8 - 12 were collected, 6 portions in each age group. If Less than 30 children in all the age groups or less than 6 in each age group, all their urine samples were collected to determine fluoride. Results Totally 3652 children aged 8 - 12 years old were examined and 1930 cases of dental fluorosis were diagnosed, the rate was 52.85% and the index was 1.22. The rates in Dinghian, Jingbian and Pucheng village were higher, being 90.43% (170/188) ,82.89%(126/152),80.65% (325/403) respectively. A total of 40 543 adults over the age of 16 were examined and 5935 cases of skeletal fluorosis were diagnosed, in a rate of 14.64%. The rates of the mild, moderate, severe skeletal fluorosis were respectively 9.17%(3717/40 543),4.36%(1769/40 543),1.11%(449/40 543).All 706 adults were taken X-ray films.and 280 cases of positive change were diagnosed,the positive rate was 39.66%. The rates of the mild,moderate,severe change were respectively 17.28%(122/706),17.00%(120/706),5.38%(38/706).All 427 water samples were collected,the fluoride content waS(2.22±1.41)ms/L,and the abnormal rate was 85.01%(363/427).All 1393 portions of urine sample were collected in children and the median of fuoride was 2.37 mg/L Conclusions The endemic fluorosis associated with drinking water is still comparatively serious in Shaanxi.The preventive measures for improving water must be improved.

OBJECTIVETo investigate hepatitis E virus (HEV) infection among pigs in Henan province.

METHODSA total of 623 swine sera, collected from 5 districts, were divided into two groups, under 3-month of age and over 3-month of age. They were tested for HEV antigen and antibody by using ELISAs, respectively. The sera positive for HEV antigen were tested for HEV RNA with RT-PCR. The positive products of RT-PCR were cloned and sequenced.

RESULTSThe positive rates of anti-HEV antibody of the groups under 3-month and over 3-month of age were 90.27% and 92.55%, respectively, without statistical difference, while those of HEV antigen were 15.93% and 5.69%, respectively, with significant difference. The positive rates of anti-HEV antibody and HEV antigen were significantly different among different districts. HEV RNA was detectable in 5 of 47 HEV antigen positive samples. The sequence analysis showed that in 4 of 5 specimens the sequence belonged to genotype 4 while in the remaining one the sequence was genotype 1.

CONCLUSIONThe prevalence rate of HEV infection in pigs was high in Henan province and the rate differed in different districts.

Animals ; Antibodies, Viral ; analysis ; immunology ; Antigens, Viral ; analysis ; immunology ; China ; Genotype ; Hepatitis E ; epidemiology ; immunology ; veterinary ; virology ; Hepatitis E virus ; genetics ; immunology ; isolation & purification ; Phylogeny ; RNA, Viral ; analysis ; genetics ; Sequence Analysis, DNA ; Swine ; virology ; Swine Diseases ; epidemiology ; immunology ; virology

This study was aimed at the transport across blood-brain barrier (BBB) of polysorbate-80 modified neurotoxin loaded polybutylcyanoacrylate nanoparticle (P-80-NT-NP) and its cytotoxicity. An in vitro model of BBB using rat brain microvascular endothelial cells (rBMECs) was established. The cytotoxicity of P-80-NT-NP was measured by the MTT assays, where neurotoxin (NT), nanoparticle (NP), neurotoxin nanoparticle (NT-NP) as control, and the permeability of P-80-NT-NP was determined by using of Millicell insert coculture with rBMECs and fluorescence spectrophotometry. MTT results showed that NT, NP, NT-NP and P-80-NT-NP were avirulent to rBMECs when the concentration of NT was lower than 200 ng x mL(-1). But the cytotoxicity of NP, NT-NP and P-80-NT-NP would be augmented accordingly as concentration increased (P < 0.01), causing obvious reductions of cell survival rate, with no significant difference between them (P > 0.05). When the concentration of NT was 150 ng x mL(-1), the permeability on rBMECs of P-80-NT-NP and NT-NP were both significantly higher than that of NT (P < 0.01), and the permeability of P-80-NT-NP was greater than that of NT-NP (P < 0.05). In conclusion, polysorbate-80 modified neurotoxin nanoparticles can transport across the BBB, while concentration of NT is greater than 200 ng x mL(-1), P-80-NT-NP has a little cytotoxicity against rBMECs.
Animals ; Biological Transport ; Blood-Brain Barrier ; Brain ; blood supply ; Capillary Permeability ; Cell Survival ; drug effects ; Cells, Cultured ; Drug Carriers ; Electric Impedance ; Enbucrilate ; chemistry ; toxicity ; Endothelial Cells ; cytology ; metabolism ; Female ; Male ; Nanoparticles ; Neurotoxins ; administration & dosage ; pharmacokinetics ; Particle Size ; Polysorbates ; chemistry ; toxicity ; Rats ; Rats, Sprague-Dawley

The study was purposed to investigate the possible mechanism of epigallocatechin-3-gallate (EGCG) induced p16 gene demethylation and transcription regulation in the malignant lymphoma cell line-CA46. The induced growth inhibition of CA46 cells was assayed by growth curve and MTT; the DNA content of CA46 cells was analyzed by flow cytometry after being exposed to EGCG; the methylation status of the p16 gene in CA46 cell line before and after treatment with EGCG was detected by the nested-methylation specific PCR and DNA sequencing; the mRNA of p16 and DNA methyltransferases (DNMT3A and DNMT3B) gene were determined by RT-PCR. The results showed that in comparison with the control, all the 3 different concentration of EGCG were able to inhibit the growth of malignancy cell lines and increase the cell number in G(0)/G(1) phase. After treatment with EGCG for 48 hours, the methylation level was apparently attenuated in a concentration-dependent manner. Expression of p16 gene in untreated group was mild while in the treated groups it had been greatly strengthened, as compared with untreated group, the gray scale ratio of p16 to beta-actin 1 treated with EGCG (6, 12, 24) microg/ml was increased from (0.05 +/- 0. 01) to (0.19 +/- 0.03), (0.39 +/- 0.10), (0.85 +/- 0.09) respectively, exhibiting a significant difference (p < 0.05); as compared with the untreated group, after treatment with EGCG for 48 hours, the expressions of DNMT3A and DNMT3B were obviously down-regulated. It is concluded that EGCG can activate and up-regulate the expression of p16 gene mRNA which inhibits the proliferation of CA46 cell through inducing the G(0)/G(1) arrest by demethylation and/or by inhibiting DNMT3A and DNMT3B gene.
Catechin ; analogs & derivatives ; pharmacology ; Cell Line, Tumor ; DNA (Cytosine-5-)-Methyltransferases ; metabolism ; DNA Methylation ; Gene Expression Regulation, Neoplastic ; Genes, p16 ; Humans ; Lymphoma ; genetics ; Transcription, Genetic

ObjectiveTo investigate the current situation of coal-burning borne endemic fluorosis in the infected area,the usage of defluoridation stove and the formation of related behavior; to evaluate the control effect,so as to provide a theoretical basis for superiors' policy-making.MethodsNine villages in three counties of Ankang city and Hanzhong city Shanxi province were monitored in 2010.Choose five disease infected villages with oven changed in the three monitoring counties,and 10 families were randomly selected in each of the nine monitoring points and every chosen village,and a survey on the stove using and related behavior changes was carried out.By using Dean method,the dental fluorosis of every child aged 8 - 12 in the monitoring villages was examined.Meanwhile 10 copies of urine samples were randomly collected in each age group in the above-mentioned villages.The content of fluoride in urine was determined by F-ion selective electrode(WS/T 30-1996) and evaluated according to “The Normal Concentration of Urinary Fluoride of Population” (WS/T 256-2005).Twenty men over 25years old in the monitoring counties were randomly selected in each age group to be examined skeletal fluorosis by X-rays,and diagnosis was based on “The Endemic Skeletal Fluorosis Standard”(WS 192-2007).ResultsThe proper utilization rate and the qualified households of iron stoves and improved stoves,the correct drying rate and the correct storage rate of peppers and coms were all low.The washing rate of corns and peppers before eating was higher than 95％.Of the 350 children being examined of dental fluorosis in the 9 monitoring villages,the detection rate of dental fluorosis was 59.71％ (209/350).A total of 871 adults over the age of 25 were examined,and the detection rate of skeletal fluorosis was 17.22％ (150/871).A total of 350 copies of children urine samples were tested and the fluoride content were between 0.07 - 2.02 mg/L,the geometric mean value of fluoride content was 0.66 mg/L.ConclusionsThe coal-burning borne endemic fluorosis in Shanxi is in a growth phase,many defluoridation stoves are out of order,and the formation of healthy behaviors is low.To strengthen the disease surveillance,health education and management of defluoridation stoves are keys to prevent coal-burning borne endemic fluorosis in the future.