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ObjectiveThe study utilized human transcriptome microarray to explore biomarkers for diagnosing drug-induced liver injury （DILI） caused by anti-tuberculosis drugs. MethodsA 6-month follow-up study was conducted on 152 patients treated with anti-tuberculosis drugs in designated hospitals in Shanghai. The blood samples were collected at the 0， 2， 4， 8， 12 and 24 weeks after treatment. According to the clinical biochemical indicators， the research subjects were divided into DILI cases （34 cases） and Control cases （118 cases）. Single factor analysis was conducted on the influencing factors between the two groups. In a 1∶1 matched DILI-control study， RNA samples of 13 pairs of cases were sequenced by the whole transcript expression mRNA array. Differentially expressed genes （DEGs） were screened by Hotelling's T2 value sequencing and the expression trend analysis of genes by STEM （short-time series expression miner）， and the functional enrichment and pathway analysis of DEGs were carried out. ResultsIn total 152 clinical cases， weight of patients was a risk factor for the occurrence of hepatotoxicity caused by anti-tuberculous drugs. Based on the analysis results of mRNA array， 513 DEGs were screened by Hotelling's T2 value sequencing method， which were enriched in 32 annotations of GO （Gene Ontology） analysis and 10 pathways of KEGG （Kyoto encyclopedia of genes and genomes） analysis. One differential expression pattern was screened by STEM， which was enriched in 2 biological process notes of GO. Among them， the key genes AIM2， CD86， CXCL10 and non-coding RNAs SCARNA10， SNHG10 and SNORD105 are potential biomarkers of DILI caused by anti-tuberculosis drugs. ConclusionIn this research for biomarkers conducted on cases with liver injury caused by anti-tuberculosis drugs， biological pathways associated with hepatotoxicity are identified and a series of key genes related with drug-induced liver injury are found， which provides the basis for mechanism study and searching for earlier and more sensitive biomarkers.
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ObjectiveThe genotoxicity of zinc oxide nanoparticles （ZnO NPs） in rats was determined by Pig⁃a mutation assay in vivo. MethodsCombined with 28-day oral toxicity test， male SD rats were given ZnO NPs by oral administration for 28 days， at doses of 0， 14， 70 and 350 mg‧kg-1 （maximum concentration of nanoscale dispersion state）. Rats in control groups received 350 mg‧kg-1 of normal size ZnO， 40 mg‧kg-1 N-ethyl-N⁃nitrosourea（ENU）or 0 mg·kg-1 ZnO NPs（solvent control group） Changes of body weight were recorded. At 0， 15， 28 d and 28 d of recovery observation period， 200 μL of tail venous blood was collected from each group， which was labeled by APC mouse anti-rat erythroid cells and FITC mouse anti-rat CD59. The information of 1×106 red blood cells（RBC） from each sample were collected by flow cytometry， and the mutation rate of RBCCD59- was calculated. ResultsCompared with the solvent control group， after 15 days of intragastric administration， the mutation rate of RBC CD59- in peripheral blood of in 350 mg‧kg-1 ZnO NPs group and 40 mg‧kg-1 ENU group was significantly increased while that of in 70 mg‧kg-1 ZnO NPs group was also significantly increased after 28 days of intragastric administration.with time-response and dose-response relationship. All groups except 40 mg‧kg-1 ENU group showed no significant difference in the mutation rate of RBCCD59- in peripheral blood in comparison with the solvent control group after 28-days recovery observation. Conclusion70 and 350 mg‧kg-1 ZnO NPs can increase the mutation rate of Pig⁃a gene in peripheral blood of SD rats.
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Objective To establish bovine corneal opacity and permeability （BCOP） test， and determine its predictive ability for the eye irritation evaluation of cosmetics. Methods A total of ten reference chemicals were selected to establish the BCOP test. Then eye irritation of 16 routinely collected cosmetics in our laboratory was predicted. In vitro scores were calculated by the change in the opacity and sodium fluorescein permeability after exposure to the testing cosmetics， and subsequently compared with the historical data by Draize test. Results Reference chemicals with known irritation classification were correctly classified by the BCOP test， which was consistent with the classification of UN globally harmonized system of classification and labeling of chemicals. Moreover， the specificity of the BCOP test for the classification of non-irritating cosmetics samples was 80.0% （8/10）， and the sensitivity for weak to mild irritating cosmetics samples was 83.3% （5/6）. The BCOP test demonstrated an overall classification consistency of 81.3% （13/16） with in vivo test. Conclusion BCOP test may be independently used to identify chemicals with potential eye irritation and serious eye damage， suggesting it is significant for in vitro integrated test strategy for predicting eye irritation due to cosmetics.
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Polyhexamethyl guanidine (PHMG) is a widely used guanidine disinfectant. Since a lung injury incident induced by humidifier disinfectant (PHMG was identified as a main component) was reported in Korea, its inhalation toxicity has attracted the attention of researchers. At present, there are few domestic studies on inhalation toxicity of PHMG. In this paper, based on the domestic and foreign studies of PHMG, the toxicities of PHMG, including inhalation toxicity and associated toxic mechanism, and other potential toxicities, such as liver toxicities, cardiovascular toxicity, immunotoxicity, and reproductive and developmental toxicity, were systematically introduced, revealing that the effects of use of PHMG in a non-standard manner on the body and its possible mechanisms, which could provide reference for the use of PHMG properly and to lay a theoretical foundation and provide a scientific basis for follow-up study.
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Heavy metals including lead, cadmium, manganese, and mercury are important raw materials and auxiliary materials in industrial production, but they are also seriously polluting the environment. While most of the early toxicological data on heavy metals are derived from studying occupational exposure populations, the general adult population and the infants and adolescents are now increasingly being studied for the health hazards of heavy metals. Epidemiological and laboratory studies have clearly demonstrated the neurotoxicity of heavy metals and sleeping is heavily regulated and coordinated by nervous system. Based on available epidemiological studies, the paper reviewed the effects of heavy metals on sleep status of occupational and non-occupational (general adults as well as infants and adolescents) populations. In addition, it presented the associated mechanisms in terms of sleep-wake cycle and sleep-related neurochemicals.
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Objective To formulate the evaluation criteria for micro-appraisal of comprehensive talents and macro-evaluation of projects.Methods A total of 425 articles were included in the meta-analysis of literature review;Delphi's panel that involved 20 experts,2 rounds of questionnaire surveys were conducted to construct indicators for comprehensive evaluation of talent construction projects;AHP was used to calculate the index weight coefficients for each category of indicators.Results The talent construction project evaluation system includes two sub-systems:micro-evaluation of talents and macro-evaluation of projects.Among them,the talent micro-evaluation system,which includes 12 evaluation indicators,carries out assessments in terms of basic qualities,academic accomplishments,and research achievements.the macro-evaluation system of the project,include a total of 15 evaluation indicators,is mainly assessed from the macro level of project operations-project structure,project process,project results.Conclusions From the perspective of the combination of micro (human resources) and macro (projects),to build a universal index for comprehensive evaluation of talent construction projects,both for the evaluation of the project,but also to conduct a comprehensive evaluation of the training object.
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<p><b>OBJECTIVE</b>To investigate the effects of fluorochloridone (FLC) exposure on the testes of adult Sprague-Dawley (SD) rats.</p><p><b>METHODS</b>Forty male SD rats were randomly divided into four groups. These groups, each of 10 male rats, were separately given FLC by gavage at a dose of 0 (control), 30, 150, or 750 mg/kg once daily for 28 d. The oxidative stress biomarkers in the testes were measured by spectrophotometry. The pathological changes in testicular tissues were evaluated under the light and electric microscopes. The cauda epididymal sperm count was determined. The testicular toxicity of FLC was assessed accordingly.</p><p><b>RESULTS</b>Compared with the control group, the 750 mg/kg FLC group had significantly lower testicular weight and organ coefficient, epididymal weight, and cauda epididymal sperm count (P < 0.05 or P < 0.01), the 150 and 750 mg/kg FLC groups had significantly increased malonaldehyde content (P < 0.05 or P < 0.01), each exposed group had a significantly reduced glutathione (GSH) level (P < 0.05 or P < 0.01), the 750 mg/kg FLC group had significantly reduced activities of superoxide dismutase (SOD), catalase (CAT), GSH peroxidase, GSH S-transferase (GSH-ST), and GSH reductase (GSH-GR) (P < 0.05 or P < 0.01), the 150 mg/kg FLC group showed significant decreases in the activities of all antioxidant enzymes except GSH-GR (P < 0.05 or P < 0.01), and the 30 mg/kg FLC group showed significant decreases in the activities of SOD and CAT (P < 0.05 or P < 0.01). Furthermore, seminiferous epithelial degeneration, Sertoli cell vacuolization, spermatogenic cell loss, and nuclear damage were observed under the light and electronic microscopes in the 150 and 750 mg/kg FLC groups.</p><p><b>CONCLUSION</b>FLC could damage the testes of adult rats by inducting oxidative stress. This research provided clues and directions for further exploration of the mechanism of FLC testicular toxicity.</p>
Subject(s)
Animals , Male , Rats , Oxidative Stress , Pyrrolidinones , Toxicity , Rats, Sprague-Dawley , Sperm Motility , Testis , Metabolism , PathologyABSTRACT
Objective To explore the mechanism of ginsenoside-Rh2(G-Rh2) on inhibition of glioma by identifying differential proteins with proteomic technique. Methods The total proteins were extracted from SHG-44 cells treated with 32 ?mol?L-1 G-Rh2 for 72 h and the cells in control group,then were subjected to two-dimensional gel electrophoresis.Only spots with a fold change equal or above 1.5 and P
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Objective To investigate the possibility and mechanism of ~ 125 I in treatment of glioma. Methods SHG-44 glioma cells were cultivated in vitro, the inhibitory effect of ~ 125 I on SHG-44 cell proliferation was determined by MTT method. The stereotactic method was used to establish the rat intracranial glioma model. The MRI was performed at 1st week after implantation and ~ 125 I was implanted in the glioma area, the MRI was performed to measure the diameter of tumor 2 weeks after implantation. The rats were killed after 2 weeks ,PCNA gene experession was determined with immunohistological method both in control and experiment group.Results one week after implantation the glioma grew,the results of MTT method showed the growth of the SHG-44 was inhibited, ~ 125 I inhibited the expression of PCNA gene and enlonged the rat survival period. Conclusion ~ 125 I can inhibit the growth of glioma ,the mechanism may be concerned with its inhibitory effect on PCNA gene expression.
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Objective To determine the effects of Tempol, one of the nitroxides, in the presence of ultraviolet-AI (UVA1, 340 nm -400 nm) on superoxide enzyme (SOD) activity, lipid peroxidation, and expression of collagen Ⅰ, collagen Ⅲ and matrix metalloproteinases (MMP)-1, MMP-3 in human dermal fi broblasts in vitro. Methods Fibroblasts were irradiated by a single exposure to UVA1 and at the same time incubated with or without Tempol, and detected 24 h later. SOD activity and lipid peroxidation, as shown by accumulation of malondialdehyde (MDA), were detected by biochemical assay. Expression of collagen Ⅰ, collagen Ⅲ (protein levels) and MMP-1, MMP-3 (mRNA level) was examined by ELISA and semi-quantitative RT-PCR, respectively. Results A dose of 15 J/cm2 UVA1 significantly inhibited SOD activity and collagen Ⅰ , collagen Ⅲ protein levels, increased MDA level and stimulated MMP-1, MMP-3 mRNA expression (P