Characterization of the nucleotide excision repair pathway and evaluation of compounds for overcoming the cisplatin resistance of non­small cell lung cancer cell lines.

Lung cancer has been reported to be the leading cause of cancer­related mortality worldwide. Cisplatin combination chemotherapy is a standard therapeutic strategy for patients with non­small cell lung cancer (NSCLC) lacking driver mutations. However, the development of cisplatin resistance is a major obstacle to effective cancer treatment. The cellular mechanisms underlying cisplatin resistance have been previously revealed to be multifunctional. Accordingly, mechanistic analysis and the development of novel therapeutic strategies for cisplatin­resistant NSCLC are urgently required. The present study mainly focused on the DNA repair mechanisms in cisplatin­resistant NSCLC cells. Additionally, the effects of an Ecteinascidin (Et) derivative on cisplatin­resistant cell lines were examined, by using a cisplatin­resistant NSCLC cell line subjected to nucleotide excision repair (NER) pathway alterations. The results revealed that xeroderma pigmentosum group F­complementing protein (XPF) mRNA expression was strongly associated with cisplatin resistance in cisplatin­resistant NSCLC cell lines. XPF silencing significantly restored the sensitivity of cisplatin­resistant PC­14/CDDP cells to the drug. A potent anticancer effect of Et was observed in the cisplatin­resistant cell line (PC­14/CDDP), in which the NER pathway was altered. On the whole, these findings revealed that the expression levels of NER pathway­related genes, including XPF, may have potential as biomarkers of cisplatin resistance. It was also suggested that Et may be a very promising compound for the development of novel anticancer drugs for the treatment of cisplatin­resistant lung cancer.

Impact of Acacia bark extract tablets on the skin of healthy humans: a randomized, double-blind, placebo-controlled study.

This study investigated the effects of proanthocyanidins derived from Acacia (Acacia mearnsii) bark extract in healthy Japanese adult subjects experiencing uncomfortable skin symptoms. All subjects were randomly allocated into two groups (n = 33 each) using a computerized random-number generator. The subjects received either Acacia bark extract tablets or placebo for 8 weeks. Evaluations included water content in the stratum corneum, transepidermal water loss (TEWL), Skindex-16, dermatology life quality index (DLQI), visual analog scale for desire to scratch, and blood tests. At 4 weeks, the symptom/feeling score of DLQI, subjective symptoms related to uncomfortable skin, and the desire to scratch were significantly reduced in the intervention group than in the placebo group. At 8 weeks, the intervention group exhibited significantly lower TEWL on facial skin than that in the placebo group. In conclusion, the intake of Acacia bark extract tablets reduced TEWL and improved dry and uncomfortable skin.

Effects of Edaravone on Hippocampal Antioxidants in EL Mice.

BACKGROUND: The role of oxidative stress in susceptibility to seizures has been the focus of several recent studies. The aim of the present study was to evaluate the antiepileptic effects of the free radical scavenger edaravone on EL mice, a strain that is highly susceptible to convulsive seizures. METHODS: EL mice were treated intraperitoneally with edaravone or saline for 1 week. The levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and 3 isozymes of superoxide dismutase (SOD) (cytoplasmic copper- and zinc-containing SOD, extracellular SOD, and mitochondrial manganese-containing SOD) were measured in the hippocampus, and electroencephalograms (EEGs) were used to evaluate seizure sensitivity. RESULTS: Hippocampal levels of GSSG were lower in the edaravone group than in the untreated control group, and the GSH/GSSG ratio, Cu/Zn-SOD, and EC-SOD activities were higher in the edaravone group. Edaravone shortened the duration of interictal spike discharges and clinically suppressed epileptic seizures. CONCLUSION: Edaravone increases antioxidant potency and reduces seizure susceptibility in EL mice, making it a promising novel antiepileptic agent.