Ecraprost

The beneficial effects of selenium on As uptake and plant growth in As-hyperaccumulator Pteris vittata are known, but the associated mechanisms remain unclear. Here, we investigated the effects of selenate on arsenic accumulation by P. vittata under two arsenate levels. P. vittata plants were exposed to 13 (As₁₃) or 133 µM (As₁₃₃) arsenate and 5 µM selenate in 0.2-strength Hoagland solution. After 14 d of growth, plant biomass, Se and As content, As speciation, and malondialdehyde (MDA), glutathione reductase (GR), glutathione peroxidase (GPX), and glutathione (GSH and GSSG) levels were determined. The results show that selenate promoted P. vittata growth and increased As concentrations in the roots and fronds by 256% from 97 to 346 mg kg^-1 and 142% from 213 to 514 mg kg^-1 under As₁₃ treatment, and by 166% from 500 to 1332 mg kg^-1 and 534% from 777 to 4928 mg kg^-1 under As₁₃₃ treatment. In addition, selenate increased the glutathione content in P. vittata roots and fronds by 75-86% under As₁₃ treatment and 44-45% under As₁₃₃ treatment. Selenate also increased the GPX activity by 161-173%, and GR activity by 72-79% in P. vittata under As₁₃ and As₁₃₃ treatments. The HPLC-ICP-MS analysis indicated that selenate increased both AsIII and AsV levels in P. vittata, with AsIII/AsV ratio being lower in the roots and higher in the fronds, i.e., more AsIII was being translocated to the fronds. Taken together, our results suggest that, via GPX-GR mediated enhancement of GSH-GSSG cycle, selenate effectively increases plant growth and As uptake in P. vittata by improving AsV reduction in the roots and AsIII translocation from the roots to the fronds.

DNA mismatch repair (MMR) deficiency has been associated with a higher risk of developing colorectal, endometrial, and ovarian cancer, and confers resistance in conventional chemotherapy. In addition to the lack of treatment options that work efficaciously on these MMR-deficient cancer patients, there is a great need to discover new drug leads for this purpose. In this study, we screened through a library of commercial and semisynthetic natural compounds to identify potential synthetic lethal drugs that may selectively target MLH1 mutants using MLH1 isogenic colorectal cancer cell lines and various cancer cell lines with known MLH1 status. We identified a novel diarylpentanoid analogue, 2-benzoyl-6-(2,3-dimethoxybenzylidene)-cyclohexenol, coded as AS13, that demonstrated selective toxicity toward MLH1-deficient cancer cells. Subsequent analysis suggested AS13 induced elevated levels of oxidative stress, resulting in DNA damage where only the proficient MLH1 cells were able to be repaired and hence escaping cellular death. While AS13 is modest in potency and selectivity, this discovery has the potential to lead to further drug development that may offer better treatment options for cancer patients with MLH1 deficiency.