三氯乙烯生物标志物的研究进展

三氯乙烯(trichloroethylene,TCE)是一种挥发性有机溶剂,主要在其制造、使用和弃置过程中释放入人类环境。在空气、水、土壤、食物和动物脏器中都有检出,人群接触量最大的为金属清洗工人,多为呼吸道吸入。检测表明目前93%通过地下水供水的公众饮水系统和9%~34%饮水用水源头均已     

大鼠体内镉负荷与尿金属硫蛋白关系的实验研究

[目的]分析大鼠尿金属硫蛋白(UMT)与体内镉负荷的关系,探讨UMT作为镉接触性生物标志物的可行性。[方法]24只SD大鼠分为4组,分别皮下注射给予0、0.5、1.0、2.0mgCd/kg体重CdCl27d。原子吸收分光光度法(AAS)测定肝脏、肾脏、胰脏、尿液、血液中镉的含量;比色法测定尿N-乙酰-β-D-氨基葡萄糖苷酶(UNAG)水平;酶联免疫吸附法(ELISA)检测UMT的含量。[结果]镉染毒大鼠血镉、尿镉、肝镉、肾镉、胰镉含量随染镉剂量的增加而明显增加,与对照组相比差异有统计学意义(P<0.05);各染镉组大鼠UNAG水平未见明显改变(P>0.05);UMT含量随着染镉剂量的增加而明显增加(P<0.05),并且与肝镉、肾镉、胰镉、血镉、尿镉含量呈明显正相关,相关系数分别为0.703、0.815、0.691、0.654、0.641(P<0.01)。[结论]UMT与体内镉负荷指标间存在较好的一致性,能反映机体镉负荷水平,可作为镉接触生物标志物。     

Continuous exposure to dibromoacetic acid delays pubertal development and compromises sperm quality in the rat.

Previously our work on the haloacid by-products of drinking water disinfection focused on adult exposures. Herein we evaluate the consequence of continuous exposure to dibromoacetic acid (DBA) via drinking water through reproductive development into adulthood. An initial study in which offspring were exposed from gestation day (GD) 15 through adulthood revealed significant delays in preputial separation and vaginal opening, dose-related decreases in the fertility of cauda epididymal sperm, and dose-related diminutions in the sperm membrane protein SP22. Subsequent studies consisted of groups in which exposure ceased on postnatal day 21 (PND 21) versus adulthood. For each exposure, animals were evaluated after puberty (PND 56) as well as at adulthood (PND 120). Exposure to 4, 40, or 400 ppm DBA from GD 15 through PND 21 failed to result in any significant reproductive alterations. By contrast, continuous exposure until adulthood resulted in dose-related alterations consistent with those observed in the dose-finding study. Preputial separation and vaginal opening were delayed 4 and 3 days in males and females exposed to 400 ppm (76.3 mg/kg) DBA. This was associated with increased responsiveness of both the testis and ovary to hCG ex vivo; hCG-stimulated testosterone production by testicular parenchyma on PND 56 was increased at 4 ppm (0.6 mg/kg) DBA and higher. Finally, the quality of proximal cauda epididymal sperm was compromised by continuous exposure to DBA. The sperm membrane proteome was altered in a dose-related manner with SP22, and one of its charged variants, diminished at 40 ppm (3.6 mg/kg) DBA and higher. As more sensitive endpoints are evaluated, lower effect levels can be attributed to haloacid exposure. We are now extending our evaluations to epidemiology studies designed to evaluate sperm quality in men exposed to varying levels of disinfection by-products.     

Found in transcription: gene expression and other novel blood biomarkers for the early detection of breast cancer

Early detection of a growing breast tumor is of key importance for patient survival. Despite limitations, mammography screening has improved the detection of breast tumors, however many tumors are not detected. This is especially true for younger women and women with high breast density. Novel diagnostic blood biomarkers either generated by the tumor and released into the blood, or generated by nontumor cells as a response to the tumor presence, can now potentially help improve the accuracy of early-stage breast cancer detection. They include multicomponent biomarkers, circulating tumor cells and RNA expression of peripheral blood. These novel biomarkers and their potential use will be presented and discussed in this review, with special emphasis on gene expression-based markers.     

Toxicity assessment and vitellogenin expression in zebrafish (Danio rerio) embryos and larvae acutely exposed to bisphenol A,endosulfan, heptachlor,methoxychlor and tetrabromobisphenol A

Organochlorine pesticides and brominated flame retardants, such as tetrabromobisphenol A and polybrominated diphenyl ethers, pose an environmental hazard owing to their persistence, low solubility and estrogenic effects, and concerns have been raised regarding their effects on aquatic biota. In the present study, zebrafish embryos and larvae were used as a model to investigate the sublethal and lethal effects of three different organochlorine pesticides, namely methoxychlor, endosulfan and heptachlor, as well as the flame retardant tetrabromobisphenol A, and its precursor compound bisphenol A. Preliminary data for chemical exposure tests were obtained by determining the 96 h median effective concentration EC₅₀ (hatching rate) and 96 h median lethal concentration LC₅₀. Quantitative polymerase chain reaction was used to investigate the gene expression levels of the biomarker vitellogenin (vtg1) after 96 h exposures to 10, 25, 50 and 75% of the 96 h EC₅₀ value for embryos and 96 h LC₅₀ value for larvae. The use of vtg1 mRNA induction in zebrafish embryos and larvae was found to be a sensitive biomarker of exposure to these organic compounds, and was helpful in elucidating their adverse effects and setting water quality guidelines. Copyright © 2012 John Wiley & Sons, Ltd.     

Structural and functional analysis of human prostatic acid phosphatase

Prostatic acid phosphatase (PAP) is the most abundant phosphatase in human prostate tissue/secretions. It is a clinically important protein for its relevance as a biomarker of prostate carcinoma. Furthermore, it has a potential role in fertilization. We describe here most of the features of PAP including gene regulation, gene/protein structure, functions, its role in tumor progression and evolutionary features. PAP has phosphatase activity and is an extensively studied biomarker of prostate cancer. The major action of PAP is to dephosphorylate macromolecules with the help of catalytic residues (His¹² and Asp²⁵⁸) that are located in the cleft between two domains. This article will be of great interest to all those scientists who are working in the area of prostate pathophysiology.     

Pharmacodynamic analysis of apremilast in Japanese patients with moderate to severe psoriasis: Results from a phase 2b randomized trial

We evaluated the pharmacodynamic effects of apremilast in 69 patients who were included in biomarker subanalyses of a phase 2b study that demonstrated the long‐term safety and efficacy of apremilast in Japanese adults with moderate to severe psoriasis. The association between cytokine levels and Psoriasis Area and Severity Index (PASI) improvement was evaluated using linear regression and Spearman’s rank correlation coefficient analysis. At baseline, median plasma levels of interleukin (IL)‐17A, IL‐17F and IL‐22 were elevated versus reference values for healthy individuals, whereas tumor necrosis factor‐α levels were close to normal. With apremilast 30 mg b.i.d., there were significant associations between percentage change in PASI score and percentage change in IL‐17A, IL‐17F and IL‐22 levels at week 16. Findings demonstrate that the efficacy of apremilast in psoriasis is associated with inhibition of key cytokines involved in the pathology of psoriasis.     

Serum vascular endothelial growth factor receptor 3 as a potential biomarker in psoriasis

To discover novel biomarkers of psoriasis, a target‐specific antibody array screening of serum samples from psoriasis patients was initially performed. The results revealed that vascular endothelial growth factor receptor 3 (VEGFR‐3) was significantly elevated in the sera of psoriasis patients, compared to healthy controls. Next, ELISA validation studies in a larger cohort of psoriasis patients (N = 73) were conducted, which confirmed that serum VEGFR‐3 was indeed significantly increased in patients with psoriasis compared to healthy controls (P < 0.001). Furthermore, receiver operating characteristic curve analysis demonstrated that serum VEGFR‐3 exhibited potential in distinguishing healthy controls from psoriasis patients: area under the curve = 0.85, P < 0.001. In addition, serum levels of VEGFR‐3 were correlated with Psoriasis Area Severity Index scores (R = 0.32, P = 0.008) in psoriasis patients. Interestingly, serum VEGFR‐3 levels were significantly elevated in psoriatic arthritis compared to non‐psoriatic arthritis (P = 0.026). A pilot longitudinal study demonstrated that serum levels of VEGFR‐3 could reflect disease progression in psoriasis. Collectively, serum VEGFR‐3 may have a clinical value in monitoring disease activity of psoriasis.