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author:("Sun, ziyang")
1.  The Effect of the Hemochromatosis (HFE) Genotype on Lead Load and Iron Metabolism among Lead Smelter Workers 
PLoS ONE  2014;9(7):e101537.
Both an excess of toxic lead (Pb) and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE) gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking.
To explore the modifying effects of the HFE genotype (wild-type, H63D variant and C282Y variant) on the Pb load and iron metabolism among Asian Pb-workers with high occupational exposure.
Seven hundred and seventy-one employees from a lead smelter manufacturing company were tested to determine their Pb intoxication parameters, iron metabolic indexes and identify the HFE genotype. Descriptive and multivariate analyses were conducted.
Forty-five H63D variant carriers and no C282Y variant carrier were found among the 771 subjects. Compared with subjects with the wild-type genotype, H63D variant carriers had higher blood lead levels, even after controlling for factors such as age, sex, marriage, education, smoking and lead exposure levels. Multivariate analyses also showed that the H63D genotype modifies the associations between the blood lead levels and the body iron burden/transferrin.
No C282Y variant was found in this Asian population. The H63D genotype modified the association between the lead and iron metabolism such that increased blood lead is associated with a higher body iron content or a lower transferrin in the H63D variant. It is indicated that H63D variant carriers may be a potentially highly vulnerable sub-population if they are exposed to high lead levels occupationally.
PMCID: PMC4079697  PMID: 24988074
2.  Pseudomonas aeruginosa inhibits the growth of pathogenic fungi: In vitro and in vivo studies 
The aim of the present study was to investigate the inhibitory effect of Pseudomonas aeruginosa (PA) on pathogenic fungi, including Candida albicans (CA), Candida tropicalis (CT), Candida glabrata (CG), Candida parapsilosis (CP) and Candida krusei (CK), in vitro and in vivo. In total, 24 PA strains were collected from clinical specimens and identified by Gram staining, oxidase production and the API 20NE system. Cross-streak, disk diffusion and co-culture methods were used to observe the inhibitory effect of PA. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to analyze differences in the bacterial proteins of PA. A blood infection model in mice was used to evaluate the effect of PA on fungi in vivo. The in vitro and in vivo results demonstrated that a number of PA isolates exhibited a marked inhibitory effect on pathogenic fungi, including CA, CT, CP, CG and CK, while other PA strains exhibited no effect. Therefore, PA exhibits an inhibitory effect on pathogenic fungi and this activity may be important in the treatment of patients. It was hypothesized that PA secretes various types of proteins to suppress the growth of fungal filaments, which subsequently inhibits pathogenic fungi.
PMCID: PMC4043586  PMID: 24926335
Pseudomonas aeruginosa; pathogenic fungi; inhibitory effect; cross-streaking method
3.  Epoxyeicosatrienoic acid-stimulated proliferation in cancer cells involves EGF-R phosphorylation mediated by activation of metalloproteinases and release of HB-EGF 
Acta pharmacologica Sinica  2010;31(2):211-218.
Arachidonic acid is metabolized to biologically active epoxyeicosatrienoic acids (EETs) by cytochrome P450 (CYP) epoxygenases. Previous studies showed that CYP epoxygenases promote neoplastic growth and induce potent mitogenic effects in human carcinoma cells; however, the exact molecular mechanisms involved in EET-induced tumor cell proliferation remain unclear. Exogenous 14,15-EET was added or a mutant CYP epoxygenase (CYP102 F87V, an active 14,15-epoxygenase) was transfected into three human derived cancer cell lines; Tca-8113, A549, HepG2 and MDA-MB-231. The effects of elevated EETs on tyrosine phosphorylation of the EGF receptor and ERK1/2 activation were then assessed. In this study, we found that addition of 14,15-EET and CYP102 F87V transfection markedly increased tyrosine phosphorylation of EGF-R and ERK1/2, an effect that was blocked by a selective EGF-R tyrosine kinase inhibitor (tyrphostin AG1478), a broad-spectrum metalloproteinase inhibitor (1,10-phenanthroline) and an inhibitor of HB-EGF release (CRM197) in Tca-8113 cells. In addition, AG1478, 1,10-phenanthroline and CRM197 also inhibited the tyrosine phosphorylation of EGF-R and ERK1/2 induced by 14,15-EET in A549, HepG2 and MDA-MB-231 cancer cell lines. These data suggest that EET-induced transactivation of EGF-R depends on activation of metalloproteinases and subsequent release of HB-EGF in cancer cells.
PMCID: PMC3938287  PMID: 20139904
arachidonic acid; cytochrome P450 epoxygenase; epoxyeicosatrienoic acids; tumor cell proliferation; EGF-R; ERK1/2; AG1478; phenanthroline; CRM197
4.  Phenotypic and Genotypic Characteristic of Invasive Pneumococcal Isolates from Both Children and Adult Patients from a Multicenter Surveillance in China 2005–2011 
PLoS ONE  2013;8(12):e82361.
Streptococcus pneumoniae is an important pathogen in both children and the elderly, but previous studies in China have provided limited information about invasive pneumococcal disease (IPD). A total of 240 IPD S. pneumoniae strains (from 105 children and 135 adults) were collected from 12 cities in China in 2005–2011. Their phenotypes and genetic characteristics were analyzed. Streptococcus pneumoniae remained highly resistant to macrolides, tetracycline, and cotrimoxazole each year. Serotypes were assigned to the 240 isolates, and 19A (22.1%), 19F (21.7%), 14 (7.5%), 3 (7.1%), and 23F (5.4%) were the most prevalent, accounting for 63.8% of all strains. Serogroup 19 strains were significantly more common among children than among adults (58.7% vs 32.4%, respectively; P < 0.001). Serotypes 19F and 19A demonstrated higher resistance to β-lactams and cephalosporins than the other serotypes. The coverage of PCV13 was superior to that calculated for PCV7 and PCV10 (77.9% vs 40.8% and 47.1%, respectively), and coverage was higher in children than in adults (85.6% vs 72.1%, respectively; P = 0.012). A multilocus sequence typing analysis revealed great diversity, with nine clonal complexes and 83 singletons among all the strains. Specifically, CC271 was more common in children, whereas singletons were more prevalent in adults. Among the serogroup 19 strains, 84.7% were ST271, ST320, or ST236, belonging to CC271. The homogeneous genetic background of 19F and 19A, together with the high resistance of these strains, suggests that clonal spread is responsible for the high prevalence of serogroup 19 in IPD. This is the first large study to investigate IPD strains in both children and adults in China.
PMCID: PMC3859574  PMID: 24349263
5.  Mycobacterium Tuberculosis-Specific TNF-α Is a Potential Biomarker for the Rapid Diagnosis of Active Tuberculosis Disease in Chinese Population 
PLoS ONE  2013;8(11):e79431.
Interferon-gamma release assays (IGRAs) have proven to be useful to accurately detect Mycobacterium tuberculosis (Mtb) infection, but they cannot reliably discriminate between active tuberculosis (TB) and latent tuberculosis infection (LTBI). This study aims to test whether Mtb-specific tumor necrosis factor-alpha (TNF-α) could be used as a new tool for the rapid diagnosis of active TB disease. The secretion of TNF-α by Mtb-specific antigen-stimulated peripheral blood mononuclear cells (PBMCs) of sixty seven participants was investigated in the study. Our results showed that the total measurement of TNF-α secretion by Mtb-specific antigen-stimulated PBMCs is not a good biomarker for active TB diagnosis. However, we found that calculation of Mtb-specific TNF-α not only distinguish between active and latent TB infection, but also can differentiate active TB from non-TB patients. Using the cutoff value of 136.9 pg/ml for Mtb-specific TNF-α, we were able to differentiate active TB from LTBI. Sensitivity and specificity were 72% and 90.91%. These data suggest that Mtb-specific TNF-α could be a potential biomarker for the diagnosis of active TB disease.
PMCID: PMC3823617  PMID: 24244502
6.  Time course of soluble P-selectin and von Willebrand factor levels in trauma patients: a prospective observational study 
Coagulopathy often develops in patients with serious trauma and is correlated with the clinical outcome. The contribution of platelet activity and endothelial dysfunction to trauma-induced coagulopathy remain to be defined. The purpose of this study was to investigate the time courses of soluble P-selectin (sPsel, an index of platelet activation) and von Willebrand factor (VWF, an index of endothelial dysfunction) in trauma patients and elucidate their relationship to coagulation parameter levels, the presence of coagulopathy, and patient outcome.
This prospective observational study, which took place in a university hospital intensive care unit (ICU), included 82 severely injured trauma patients. The sPsel, VWF antigen, protein C, and factor VII levels were measured and routine coagulation tests were performed upon admission to ICU and daily within the first week. The 30-day mortality rate was also determined.
Thirty-seven (45.1%) patients developed coagulopathy upon admission to the ICU, and the 30-day mortality rate was 20.7% (n = 17). Both the admission sPsel and VWF levels were lower in patients with coagulopathy than in those without (p < 0.05) and were significantly correlated with the protein C and factor VII levels, respectively (all p < 0.05). The VWF levels were lower during the first 3 days and higher on day 7 after admission in nonsurvivors than in survivors (all p < 0.05). No significant differences in sPsel levels were found between nonsurvivors and survivors on each day during the first week.
In severely injured trauma patients in the ICU, lower levels of sPsel and VWF on admission were associated with the presence of coagulopathy and might not predict a better outcome. An increase in the VWF level at the end of the first week after admission to ICU was associated with increased 30-day mortality.
PMCID: PMC3847632  PMID: 24034700
Soluble P-selectin; von Willebrand factor; Trauma; Trauma-induced coagulopathy
7.  High Prevalence of Fluoroquinolone-Resistant Group B Streptococci among Clinical Isolates in China and Predominance of Sequence Type 19 with Serotype III 
A total of 146 group B streptococcus isolates from 8 cities across China belonged to four serotypes. Serotype Ia was more common in children. A high prevalence of resistance was observed for levofloxacin (37.7%), erythromycin (71.2%), clindamycin, (53.4%), and tetracycline (81.5%). The levofloxacin and clindamycin resistances among the 4 serotypes differed significantly. Eighty percent of fluoroquinolone-resistant isolates belonged to the sequence type 19 (ST19)/serotype III clone, with GyrA-ParC-ParE triple substitutions. This clone carried the erm(B), mef(E), and tet(M) genes.
PMCID: PMC3591929  PMID: 23295933
9.  Ciprofloxacin-Resistant Salmonella enterica Serotype Typhimurium, China 
Emerging Infectious Diseases  2008;14(3):493-495.
We characterized 44 Salmonella enterica serotype Typhimurium isolates from Tongji Hospital outpatients in Wuhan, China, May 2002–October 2005. All 31 ciprofloxacin-resistant isolates were also resistant to >8 other antimicrobial drugs and carried >2 mutations in GyrA and 1 mutation in ParC. Class 1 integrons were identified in 37 isolates.
PMCID: PMC2570801  PMID: 18325271
Salmonella Typhimurium; outpatients; ciprofloxacin; resistance; dispatch

Results 1-9 (9)