A dose-response experiment was conducted to find the sensitive and consistent biomarker for the estimation of dietary manganese (Mn) requirement and establish the optimal Mn level for broilers fed a practical corn-soybean meal diet from 1 to 21 days of age post-hatching. A total of 480 1-day-old Arbor Acres male chicks were randomly allotted to one of eight treatments with five replicates of 12 birds each and fed diets supplemented with 0, 20, 40, 60, 80, 100, 120, or 140 mg Mn/kg from reagent grade Mn sulfate. Tissue Mn concentrations, manganese-containing superoxide dismutase (MnSOD) activity, and MnSOD mRNA concentration within heart tissue were analyzed at 7, 14, and 21 days of age. Tissue Mn concentrations and heart MnSOD activity showed significant quadratic responses, and heart MnSOD mRNA concentration showed an asymptotic response to dietary supplemental Mn level, respectively. The estimate of dietary Mn for chicks from 1 to 21 days of age was 122-128 for heart Mn concentration, 141-159 for pancreas Mn concentration, 127-138 for liver Mn concentration, and 135-156 mg/kg for heart MnSOD activity, respectively. Heart MnSOD mRNA concentration was a consistent index for the estimation of the Mn requirement of broilers. Based on this index, the estimate of dietary Mn requirement for broilers from 1 to 21 days of age post-hatching was about 130 mg/kg, which was a little more than two times of the current NRC (1994) requirement.

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Abstract. Tumor metastasis is the main cause of mortality in cancer patients. However, no effective therapies are currently available to prevent metastasis. Cell adhesion to the extracellular matrix (ECM) is crucial in cancer progression and metastasis. Thus, suppression of cell adhesion may be an effective therapeutic strategy for the prevention of metastasis. In the present study, the anti-adhesion and anti-invasion effects of jolkinolide B, a diterpenoid compound from Euphorbia fischeriana Steud, that were exerted through suppression of β 1 -integrin expression and phosphorylation of focal adhesion kinase (FAK) were examined in human breast cancer MDA-MB-231 cells. Jolkinolide B inhibited the adhesion of MDA-MB-231 cells to fibronectin but not to poly-L-lysine. In addition, jolkinolide B inhibited extracellular signal-regulated kinase (ERK) phosphorylation. U0126, an ERK inhibitor, also suppressed the invasion and adhesion of MDA-MB-231 cells. Overall, the present data demonstrated that jolkinolide B is a novel inhibitor of FAK-mediated signaling pathways that is involved in decreasing cell adhesion and invasion. Mitogen-activated protein kinase/ERK kinase may play a critical role in these effects, indicating that jolkinolide B possesses therapeutic potential for the treatment of breast cancer metastasis.

Inspired by the significant bioactivity of ergosterol peroxide, we designed and synthesized four fluorescent coumarin and ergosterol peroxide conjugates 8a–d through the combination of ergosterol peroxide with 7-N,N-diethylamino coumarins fluorophore. The cytotoxicity of synthesized conjugates against three human cancer cells (HepG2, SK-Hep1, and MCF-7) was evaluated. The results of fluorescent imaging showed that the synthesized conjugates 8a–d localized and enriched mainly in mitochondria, leading to significantly enhanced cytotoxicity over ergosterol peroxide. Furthermore, the results of biological functions of 8d showed that it could suppress cell colony formation, invasion, and migration; induce G2/M phase arrest of HepG2 cells, and increase the intracellular ROS level.