Up to the end of the second trimester, iodine treatment protects the fetal brain from the effects of iodine deficiency. Treatment later in pregnancy or after delivery may improve brain growth and developmental achievement slightly, but it does not improve neurologic status.

Endoplasmic reticulum stress-mediated cell apoptosis is implicated in the development of cancer. Melatonin induces apoptosis in hepatocellular carcinoma (HCC) in experimental studies, but the effects of melatonin on endoplasmic reticulum (ER) stress-induced apoptosis in HCC have not been tested. Differences in ER stress-induced apoptosis in human hepatoma cells and normal human hepatocyte were investigated by exposure to tunicamycin (ER stress inducer). Significant differences were observed in the rate of apoptosis between HepG2 cells (hepatoma cells) and HL-7702 cells (normal human hepatocyte cells). The expression of cyclooxygenase-2 (COX-2) was increased in HepG2 cells but not in HL-7702 cells. Furthermore, down-regulation of COX-2 expression using the COX-2 inhibitor, celecoxib, increased tunicamycin-induced apoptosis concomitant with the up-regulation of pro-apoptotic transcription factor CHOP (GADD153) and down-regulation of B-cell lymphoma 2/Bcl-2-associated X protein (Bcl-2/Bax) ratio, suggesting that inhibition of COX-2 sensitized human hepatoma cells to ER stress-induced apoptosis. Interestingly, co-treatment with tunicamycin and melatonin also decreased the expression of COX-2 and significantly increased the rate of apoptosis by elevating the levels of CHOP and reducing the Bcl-2/Bax ratio. These results demonstrate that melatonin sensitizes human hepatoma cells to ER stress-induced apoptosis by down-regulating COX-2 expression, increasing the levels of CHOP and decreasing the Bcl-2/Bax ratio.

Abstract. Worldwide research contributions have allowed the field of fracture surgery to progress. However, to the best of our knowledge, no studies have documented the main characteristics of publications from different countries. The present study aimed to determine the quantity and quality of worldwide research in fracture surgery. The Web of Science database was searched to identify fracture articles published between 2005 and 2014. The contributions of countries were evaluated based on paper and citation numbers, and the research output of each country was adjusted according to population size.

Chemoresistance in hepatocellular carcinoma (HCC) is associated with multiple cellular responses to environmental stresses, such as nutrient deprivation and hypoxia. Nevertheless, whether ER stress resulting from nutrient deprivation and tumor hypoxia contributes to drug resistance remains unclear. Melatonin increased the efficacy of chemotherapeutic drugs in hepatocellular carcinoma in our previous studies. However, the effects of melatonin on endoplasmic reticulum (ER) stress-induced resistance to chemotherapeutic agents in HCC have not been tested. The effect of the endoplasmic reticulum (ER) stress response during resistance of human hepatocellular carcinoma cells against doxorubicin was investigated in this study. Pretreatment of HepG2 and SMMC-7721 cells (two human hepatocellular carcinoma cell lines) with tunicamycin, an ER stress inducer, drastically decreased the rate of apoptosis generated by doxorubicin. Interestingly, co-pretreatment with tunicamycin and melatonin significantly increased apoptosis induced by doxorubicin. Simultaneously, the expression of phosphorylated AKT (p-AKT) was elevated in HepG2 and SMMC-7721 cells given tunicamycin but reduced in the presence of melatonin. Furthermore, consistent with inhibition of AKT activation by using the PI3K inhibitor LY294002, melatonin elevated the levels of CHOP (C/EBP-homologous protein) and reduced the levels of Survivin (a member of the inhibitor of apoptosis protein family)suggesting that inhibition of the PI3K/AKT pathway by melatonin-reversed ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells. These results demonstrate that melatonin attenuates ER stress-induced resistance to doxorubicin in human hepatocellular carcinoma cells by down-regulating the PI3K/AKT pathway, increasing the levels of CHOP and decreasing the levels of Survivin.

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