Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) in paired maternal and neonatal samples from South China: Placental transfer and potential risks.

Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are attracting more and more attention for the neurodevelopment toxicity effects. We evaluated the concentrations of 15 individual OH-PBDEs and 3 bromophenol (BRP) congeners in 30 mother-newborn paired placenta, breast milk, fetal cord blood, and neonatal urine samples collected from South China. The geometric mean (GM) concentrations of ∑OH-PBDEs were 37.6, 61.3, and 76.8pgg(-1) ww in placenta, breast milk, and cord blood, respectively. The GM concentrations of ∑BRPs were 47.6, 119, and 30.2pgg(-1) ww in placenta, breast milk, and cord blood, respectively. The GM concentrations of ∑OH-PBDEs and ∑BRPs in neonatal urine were 72.0 and 79.8pgml(-1), respectively. Of the 15 OH-PBDE congeners analyzed, the three most frequently detected congeners were 2'-OH-BDE-68 (72.1%), 6-OH-BDE-47 (67.6%), and 2'-OH-BDE-28 (65.8%). The estimated daily intake (EDI) of OH-PBDEs for the breast-fed infants was 9.31±4.00ngkg(-1) bw day. The accumulation of OH-PBDEs in newborns was much lower than the estimated lowest observed-effect concentration (LOEC) of neurotoxicity. The present study provided the first systematic fundamental data that exposure to OH-PBDEs for newborn and their mothers in South China.

Inverse agonist of estrogen-related receptor α suppresses the growth of triple negative breast cancer cells through ROS generation and interaction with multiple cell signaling pathways.

There is an urgent clinical need for targeted therapy approaches for triple-negative breast cancer (TNBC) patients. Increasing evidences suggested that the expression of estrogen-related receptor alpha (ERRα) was correlate with unfavorable clinical outcomes of breast cancer patients. We here show that inhibition of ERRα by its inverse agonist XCT-790 can suppress the proliferation, decrease G2/M phases, and induce mitochondrial-related apoptosis of TNBC cells. XCT-790 elevates the proteins related to endoplasmic reticulum (ER) stress such as ATF4/6, XBT-1 and CHOP. It also increases the expression of growth inhibition related proteins such as p53 and p21. Further, XCT-790 can increase the generation of reactive oxygen species (ROS) in TNBC cells mainly through inhibition of SOD1/2. While ROS scavenger NAC abolishes XCT-790 induced ER-stress and growth arrest. XCT-790 treatment can rapidly activate the signal molecules including ERK1/2, p38-MAPK, JNK, Akt, p65, and IκBα, while NAC attenuates effects of XCT-790 induced phosphorylation of ERK1/2, p38-MAPK and Akt. Further, the inhibitors of ERK1/2, JNK, Akt, and NF-κB attenuate XCT-790 induced ROS generation. These data suggest that AKT/ROS and ERK/ROS positive feedback loops, NF-κB/ROS, and ROS/p38-MAPK, are activated in XCT-790 treated TNBC cells. In vivo experiments show that XCT-790 significantly suppresses the growth of MDA-MB-231 xenograft tumors, which is associated with up regulation of p53, p21, ER-stress related proteins while down regulation of bcl-2. The present discovery makes XCT-790 a promising candidate drug and lays the foundation for future development of ERRα-based therapies for TNBC patients.

Bisphenol A modulates colorectal cancer protein profile and promotes the metastasis via induction of epithelial to mesenchymal transitions.

More and more evidences indicate that endocrine disruptor chemicals such as bisphenol A (BPA) can act as carcinogens and enhance susceptibility to tumorigenesis. Although the gut is in direct contact with orally ingested BPA, effects of BPA on occurrence and development of colorectal cancer remain an unexplored endpoint. Colorectal cancer SW480 cells treated with nanomolar (10(-8) M) or greater (10(-5) M) concentrations of BPA were compared with responses of a control group. Proteomic study revealed that more than 56 proteins were modulated following exposure to BPA, which are relevant to structure, motility and proliferation of cells, production of ATP, oxidative stress, and protein metabolism. Further studies revealed that BPA increased migration and invasion and triggered transformations from epithelial to mesenchymal transitions (EMTs) of colorectal cancer cells, which was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin with a concomitant decrease of E-cadherin. Accordingly, BPA treatment increased the expression of transcription factor Snail. Furthermore, signal AKT/GSK-3ß-mediated stabilization of Snail is involved during BPA-induced EMT of colon cancer cells. Our study first demonstrated that the xenoestrogen BPA at nanomolar and greater concentrations modulates the protein profiles and promotes the metastasis of colorectal cancer cells via induction of EMT.

Signaling related with biphasic effects of bisphenol A (BPA) on Sertoli cell proliferation: a comparative proteomic analysis.

BACKGROUND: Biphasic effects on cell proliferation of bisphenol A (BPA) can occur at lesser or greater exposures. Sertoli cells play a pivotal role in supporting proliferation and differentiation of germ cells. The mechanisms responsible for inverse effects of great and low concentrations of BPA on Sertoli cell proliferation need further study. METHODS: We utilized proteomic study to identify the protein expression changes of Sertoli TM4 cells treated with 10(-8)M and 10(-5)M BPA. The further mechanisms related to mitochondria, energy metabolism and oxidative stress were investigated by qRT-PCR and Western-blotting analysis. RESULTS: Proteomic studies identified 36 proteins and two major clusters of proteins including energy metabolism and oxidative stress expressed with opposite changes in Sertoli cells treated with 10(-8)M and 10(-5)M BPA, respectively, for 24h. Exposure to 10(-5)M BPA resulted in greater oxidative stress and then inhibited cell proliferation, while ROS scavenger NAC effectively blocked these effects. Exposure to 10(-8)M BPA caused higher intercellular ATP, greater activities of mitochondria, and resulted in significant proliferation of TM4 cells, while oligomycin A, an inhibitor of ATP synthase, abolished these growth advantages. CONCLUSIONS: Our study demonstrated that micromolar BPA inhibits proliferation of Sertoli cells by elevating oxidative stress while nanomolar BPA stimulates proliferation by promoting energy metabolism. GENERAL SIGNIFICANCE: Micromolar BPA inhibits cell proliferation by elevating oxidative stress while nanomolar BPA stimulates cell proliferation by promoting energy metabolism.

Involvement of activating ERK1/2 through G protein coupled receptor 30 and estrogen receptor α/ß in low doses of bisphenol A promoting growth of Sertoli TM4 cells.

Sertoli cells play a pivotal role in supporting proliferation of germ cells and differentiation during spermatogenesis in mammals. Nanomolar concentrations of Bisphenol A (BPA) can significantly stimulate the proliferation of mouse immature Sertoli (TM4) cells. However, mechanisms by which BPA caused these effects were still unclear. In the present study, an inverse U-shaped curve was observed when treating TM4 cells with increasing doses of BPA: 1 to 10nM BPA significantly stimulated the proliferation of TM4 cells and increased the proportion of cells in S phase; >1 µM BPA caused lesser proliferation of cells. Exposure of TM4 cells to G15 or ICI 182,780, which are specific antagonists of GPR30 and estrogen receptor α/ß (ERα/ß), respectively, abolished BPA-induced proliferation of cells, which suggests that both GPR30 and ERα/ß were involved in the observed effects of BPA. Furthermore, exposure to BPA caused rapid (5 min) activation of ERK1/2 via both GPR30 and ERα/ß. Blocking the GPR30/EGFR signal transduction pathway by antagonists suppressed both phosphorylation of ERK and BPA-induced cell proliferation. BPA up-regulated mRNA and protein expression of GPR30 in a concentration-dependent manner. In summary, the results reported here indicated that activating ERK1/2 through GPR30 and ERα/ß is involved in low doses of BPA that promoted growth of Sertoli TM4 cells. The GPR30/EGFR/ERK signal is the downstream transduction pathway in BPA-induced proliferation of TM4 Sertoli cells.

[Internal fixation for the treatment of anteromedial facet fracture of the coronoid process of ulna].

OBJECTIVE: To investigate the effect of operative treatment for anteromedial facet fracture of the coronoid process of ulna,and to study its surgical exposures and fixation techniques. METHODS: From March 2005 to March 2010,18 patients with anteromedial facet fracture of the coronoid process of ulna were treated with open reduction and internal fixation. There were 12 males and 6 females with an average age of 37.8 years. A single midline posterior incision was used to expose the entire elbow joint. After elevating the full-thickness skin flaps, a lateral incision was made to expose and repair the lateral collateral ligament. Three intervals in the flexor-pronator musculature were used to gain access to the coronoid,depending on the size of the fracture fragment and the planned fixation technique. Fractures were fixed by using mini-plate or with screws. The therapeutic effects were evaluated by Mayo Elbow Performance Score (MEPS) and system of Broberg & Morrey. RESULTS: Seventeen patients were followed up, no patient complained pain and elbow unstable at a mean follow-up period of 38 months(1 to 6 years). The fractures were clinically healed at an average time of 11.6 weeks(ranged from 8 to 16 weeks). The average MEPS was 95.4+/-4.6 (ranged, 82 to 100). The average functional rating of system of Broberg & Morrey was 92.3+/-5.8 (ranged,75 to 100). CONCLUSION: Open reduction and internal fixation is effective to reach anatomical reduction and strong fixation for the treatment of anteromedial facet fracture of the coronoid process of ulna.

[Clinical application of the combination of postural reduction and kyphoplasty for traumatic thoracolumbar spine fractures].

OBJECTIVE: To determine the efficacy and feasibility of the combination of postural reduction and percutaneous kyphoplasty for traumatic thoracolumbar spine fractures. METHODS: Thirty-seven patients with single level traumatic thoracolumbar spine fractures were included in this study. There are 28 males and 9 females, with an average age of 48 years (range 24 to 79 years). Patients were treated with postural reduction and then percutaneous vertebroplasty with Calcium Phosphate Cement (CPC) were performed on the fractured vertebra. The results were quantitatively evaluated, according to the concept of estimated vertebral height loss and kyphotic angle of the vertebral fractures by preoperative and postoperative plain standing lateral radiographs. Visual analog scale (VAS) and the fracture vertebra shape changes were recorded. RESULTS: Patients were followed up for 9 to 24 months (average 13 months), pain was significantly relieved compared with the preoperative, VAS was reduced averagely from 7.6 +/- 2.5 to 1.8 +/- 1.5, the anterior and middle vertebral height was restored and kyphotic angle was corrected. During the period of follow up, outcomes were satisfactory, without notable correction loss. CONCLUSION: If the indications are correctly handled, the combination of postural reduction and percutaneous kyphoplasty for the treatment of traumatic thoracolumbar spine fractures can provide significant pain relieve and restore the vertebral height and kyphotic angle.

[Treatment of chronic osteomyelitis with antibiotic-loaded calcium phosphate cement].

The antibiotic delayed release system which has the characteristics of high local antibiotic concentration,few adverse effects, slow release and long duration, has became one of important methods of treating chronic osteomyelitis. Because of its double action as drug carrier and bone repair material which can induce bone growth and degrade synchronously, drug impregnated calcium phosphate cement (diCPC) is an ideal and safe antibiotic slow release carrier. After clearing focus thoroughly, defect implant with diCPC is an effective method, which has the virtues of convenient operation, good effects and short staying time etc. This paper aims to summarize the biological properties, experimental study and clinical application of diCPC.