Beijing Institute of Disease Control and Prevention
Beijing Institute of Disease Control and Prevention
Yang H.,China Institute of Technology |
Zhang W.,China Institute of Technology |
Kong Q.,Pharmaron Preclinical Services Laboratories |
Liu H.,China Institute of Technology |
And 4 more authors.
Food and Chemical Toxicology | Year: 2013
Thiazole-Zn is a newly chinese-created systemic fungicide, and belongs to the sort of thiadiazole compounds, some of which have been found to be thyroid disrupters. To determine the probable adverse effects of thiazole-Zn on thyroid gland and development function, the rodent 20-day Pubertal Female Assay in this study was used. Postnatal days (PND) 22-old Sprague-Dawley rats were administered with thiazole-Zn daily by oral gavage at doses 0, 40, 100, 200. mg/kg/day for 20. days. The thyroid endpoints and development endpoints were assessed. The results indicated that serum TT4 and TSH levels were significantly increased at all concentrations, serum TT3 levels were significantly reduced only at 40. mg/kg thiazole-Zn, but had no difference from controls at the other doses. Thyroid histology was significantly altered at all doses with a clear dose-dependent hypertrophy and hyperplasia of thyroid cell. No histological changes were observed in any of the other observed organs. In addition, this study also found that ovarian weights were significantly decreased, but age and weight at vaginal opening (VO), serum E2 levels were unaffected in all treatment groups. These results demonstrate that thiazole-Zn is likely a thyroid disrupter, but did not demonstrate that it has estrogenic/anti-estrogenic activity. © 2012 Elsevier Ltd.
Li D.,Beijing Institute of Biotechnology |
Dong Q.,Beijing Institute of Biotechnology |
Tao Q.,Anhui University |
Gu J.,Beijing Institute of Biotechnology |
And 10 more authors.
Cell Reports | Year: 2015
The ubiquitin-proteasome system is a vital proteolytic pathway required for cell homeostasis. However, the turnover mechanism of the proteasome subunit itself is still not understood. Here, we show that the 20S proteasome subunit PSMA7 is subjected to ubiquitination and proteasomal degradation, which was suppressed by PSMA7 phosphorylation at Y106 mediated by the nonreceptor tyrosine kinases c-Abl/Arg. BRCA1 specifically functions as an E3 ubiquitin ligase of PSMA7 ubiquitination. c-Abl/Arg regulates cellular proteasome abundance by controlling the PSMA7 subunit supply. Downregulated PSMA7 level results in decreased proteasome abundance inc-Abl/Arg RNAi-knockdown or c-abl/. arg-deficient cells, which demonstrated an increased sensitivity to proteasome inhibition. In response to oxidative stress, the c-Abl-mediated upregulation of proteasome level compensates for the proteasomal activity impairment induced by reactive oxygen species. Abl-kinases-regulated biogenesis and homeostasis of proteasome complexes may be important for understanding related diseases and pathological states. © 2015 The Authors.
Wang Y.,Bayi Childrens Hospital |
Zhang X.-A.,Beijing Institute of Microbiology and Epidemiology |
Yang X.,Bayi Childrens Hospital |
Yang X.,Shanghai University |
And 2 more authors.
Molecular Genetics and Genomics | Year: 2014
Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine involved in the pathogenesis of spontaneous preterm birth (SPTB). We examined whether the MCP-1 G-2518A polymorphism is associated with the risk of SPTB in a Chinese population. The MCP-1 G-2518A polymorphism was genotyped in 569 preterm singleton neonates and in 673 term neonates using polymerase chain reaction–restriction fragment length polymorphism analysis. The distribution of the MCP-1 G-2518A genotype and the allele frequencies between the SPTB patients and the controls were not significantly different in the overall sample. However, we found that the AA genotype was associated with significantly increased susceptibility to very SPTB (<32 weeks) [odds ratio (OR) 2.07; 95 % confidence interval (CI), 1.27–3.36; P = 0.005) and extremely SPTB (<28 weeks) (OR 2.74; 95 % CI, 1.10–6.72; P = 0.014) compared with −2518G-positive genotypes (GG + GA genotypes). When extremely preterm neonates and very preterm neonates were combined, the AA genotype was also significantly associated with increased susceptibility to SPTB (OR 2.23; 95 % CI, 1.40–3.54; P < 0.001). The MCP-1 G-2518A polymorphism was not associated with increased susceptibility to SPTB in patients with premature rupture of the membranes (PROM) or in those without PROM. Our findings suggest that the MCP-1 G-2518A polymorphism may plays a role in mediating the susceptibility to SPTB in the Chinese population. Knowledge of genetic factors contributing to the pathogenesis of SPTB may have implications for screening and treatment of this disorder. © 2014, Springer-Verlag Berlin Heidelberg.
PubMed | Beijing Normal University, Beijing Institute of Biotechnology and Beijing Institute of Disease Control and Prevention
Type: | Journal: Free radical biology & medicine | Year: 2016
Oxidative stress contributes to the oxidative modification of cellular components, including lipids, proteins and DNA, and results in DNA damage, cell cycle arrest, cellular dysfunction and apoptosis. However, the mechanism underlying oxidative stress-induced mitotic abnormalities is not fully understood. In this study, we demonstrated that exogenous and endogenous reactive oxygen species (ROS) promoted mitotic arrest. Delayed formation and abnormal function of the mitotic spindle, which directly impeded mitosis and promoted abnormal chromosome separation, was responsible for ROS-induced mitotic arrest. As a key regulator of mitotic spindle assembly, Aurora A kinase was hyperphosphorylated in early mitosis under oxidative stress, which may disturb the function of Aurora A in mitotic spindle formation. Our findings identified a mechanism by which ROS regulate mitotic progression and indicated a potential molecular target for the treatment of oxidative stress-related diseases.
Zhong Z.,Sichuan Agricultural University |
Zhong Z.,Beijing Institute of Disease Control and Prevention |
Yu S.,Sichuan Agricultural University |
Wang X.,Anhui Agricultural University |
And 6 more authors.
International Journal of Infectious Diseases | Year: 2013
Brucellosis is a worldwide re-emerging zoonotic disease. It remains a serious public health problem in many developing countries including China. This review summarizes the epidemiological characteristics, morbidity, and endemic distributions of human brucellosis in the People's Republic of China for the period 2005-2010. From 2005 to 2010, the incidence of human brucellosis rose substantially in China, especially in the provinces of Inner Mongolia, Shanxi3, Heilongjiang, Hebei, Jilin, and Shanxi1. Meanwhile human brucellosis increased gradually in some southern provinces, such as Henan, Guangdong, and Fujian. Due to the rapid expansion of human brucellosis in China, surveillance and prevention of this disease has been greatly challenged. © 2013 International Society for Infectious Diseases.
Wei Q.-H.,Beijing Institute of Pharmacology and Toxicology |
Wei Q.-H.,Beijing Institute of Disease Control and Prevention |
Wu N.,Beijing Institute of Pharmacology and Toxicology |
Bian J.-M.,Beijing Institute of Pharmacology and Toxicology |
And 3 more authors.
Addiction Biology | Year: 2013
Drug addiction is thought to result from an intractable and aberrant learning and memory in response to drug-related stimulation, and cholinergic neurotransmission plays an important role in this process. Phosphatidylethanolamine-binding protein (PEBP) is the precursor of the hippocampal cholinergic neurostimulating peptide (HCNP), an 11 amino acid peptide that enhances the production of choline acetyltransferase (ChAT) and assists in the development of cholinergic projections from the medial septal nuclei to the hippocampus. However, whether PEBP is involved in drug addiction remains unclear. In the present study, PEBP expression in the hippocampus, as detected by proteomics analysis, was found to be dramatically up-regulated after rats received chronic morphine treatment. Western blotting analysis revealed a specific up-regulation of PEBP expression in the hippocampus but not in any other brain regions assessed. A down-regulation of hippocampal PEBP levels induced by antisense oligodeoxynucleotides resulted in aggravated morphine dependence. Together, these findings indicate that PEBP is involved in morphine dependence. Moreover, the time course of PEBP expression changes and ChAT activity was investigated during chronic morphine treatment and withdrawal. The results showed that the hippocampal PEBP levels were up-regulated during chronic morphine treatment and returned to the baseline 3 days after withdrawal, after which PEBP levels were persistently up-regulated for 28 days after withdrawal. The changes in hippocampal ChAT activity followed a pattern that was similar to that of the PEBP levels. Taken together, these results suggest that hippocampal PEBP is involved in morphine dependence and withdrawal, perhaps through modulating cholinergic transmission in the hippocampus. © 2011 Society for the Study of Addiction.
Yuxia W.,Beijing Institute of Pharmacology and Toxicology |
Lijun Y.,Beijing Institute of Pharmacology and Toxicology |
Lijun Y.,Beijing Institute of Disease Control and Prevention |
Qin L.,Beijing Institute of Pharmacology and Toxicology |
And 2 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2011
A simple, fast, sensitive and robust method for the determination of the sulfur mustard (SM) exposure biomarker-N 7-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (HETEG) was reported using high-performance liquid chromatography-positive electrospray tandem mass spectrometry (HPLC-ESI-MS/MS), working in multiple reaction monitor (MRM) mode. The method provided limit of detection of 0.330ng/mL and lower limit of quantitation of 0.940ng/mL. The method was linearly calibrated from 0.940ng/mL to 587ng/mL with precisions of 3.5-14.5%, and accuracies of 88-112%. The recovery varied from 102% to 118%. HETEG spiked in DNA hydrolytes isolated from the human whole blood was stable after five freeze/thaw cycles and 35-day frozen at -20°C. For the exposed biological samples, alkylated DNA was isolated from SM-treated human whole blood, followed by DNA digestion and adducts enrichment, the resulting alkylation base was determined. By the procedure, the HETEG level in DNA hydrolytes isolated from the human whole blood exposure to 312ng/mL SM was detected successfully. © 2011 Elsevier B.V.
Feng Y.,Urbana University |
Feng Y.,Zhejiang University |
Xu J.,Beijing Institute of Disease Control and Prevention |
Zhang H.,Urbana University |
And 2 more authors.
Journal of Bacteriology | Year: 2013
The enzyme cofactor biotin (vitamin H or B7) is an energetically expensive molecule whose de novo biosynthesis requires 20 ATP equivalents. It seems quite likely that diverse mechanisms have evolved to tightly regulate its biosynthesis. Unlike the model regulator BirA, a bifunctional biotin protein ligase with the capability of repressing the biotin biosynthetic pathway, BioR has been recently reported by us as an alternative machinery and a new type of GntR family transcriptional factor that can repress the expression of the bioBFDAZ operon in the plant pathogen Agrobacterium tumefaciens. However, quite unusually, a closely related human pathogen, Brucella melitensis, has four putative BioR-binding sites (both bioR and bioY possess one site in the promoter region, whereas the bioBFDAZ [bio] operon contains two tandem BioR boxes). This raised the question of whether BioR mediates the complex regulatory network of biotin metabolism. Here, we report that this is the case. The B. melitensis BioR ortholog was overexpressed and purified to homogeneity, and its solution structure was found to be dimeric. Functional complementation in a bioR isogenic mutant of A. tumefaciens elucidated that Brucella BioR is a functional repressor. Electrophoretic mobility shift assays demonstrated that the four predicted BioR sites of Brucella plus the BioR site of A. tumefaciens can all interact with the Brucella BioR protein. In a reporter strain that we developed on the basis of a double mutant of A. tumefaciens (the ΔbioR ΔbioBFDA mutant), the β-galactosidase (β-Gal) activity of three plasmid-borne transcriptional fusions (bioBbme-lacZ, bioYbme-lacZ, and bioRbme-lacZ) was dramatically decreased upon overexpression of Brucella bioR. Real-time quantitative PCR analyses showed that the expression of bioBFDA and bioY is significantly elevated upon removal of bioR from B. melitensis. Together, we conclude that Brucella BioR is not only a negative autoregulator but also a repressor of expression of bioY and bio operons that separately function in biotin transport and the biosynthesis pathway. © 2013, American Society for Microbiology.
Guo J.-B.,Beijing Institute of Disease Control and Prevention |
Peng H.,Beijing Institute of Disease Control and Prevention |
Wang Y.-M.,Beijing Institute of Disease Control and Prevention |
Peng S.-Q.,Beijing Institute of Disease Control and Prevention
Chinese Journal of New Drugs | Year: 2012
Mitochondria are the major sources of cellular energy and reactive oxygen species (ROS), playing fundamental roles in regulation of cell survival and death under pathological conditions. Mitochondria are important targets of drug toxicity. A variety of drugs, eg. antivirals, anti-cancer drugs, and antibiotics, have been shown to significantly induce mitochondrial toxicity in targeted organs such as liver and heart. Drug-induced mitochondrial injury may involve multiple pathways and mechanisms. Recently, it has been suggested that mitochondrial toxicity is the main cause leading to the failure of drug development, and many post-market drugs that have been withdrawn or received Black Box warnings from the FDA are characterized by mitochondrial toxicity. Thus, assessment of mitochondrial toxicity is of great significance in the research and development of innovative drugs.
Wang Y.,Beijing Institute of Disease Control and Prevention
Journal of bacteriology | Year: 2012
Brucella canis is considered a rare cause of human brucellosis because of difficulties in presumptive diagnosis and underestimation of the incidence. Here, we report the draft genome sequence of a Brucella canis isolate, BCB018, isolated from a human patient, providing precious resources for comparative genomics analysis of Brucella field strains.