Analysis of lichen substances including triterpenoids by high performance liquid chromatography with a differential refractive index detector and a photodiode array detector

A new method for analysis of lichen triterpenoids was established using high performance liquid chromatography with the combination of a differential refractive index detector (RID) and a photodiode array detector (PDA). It is proved that this method was convenient to detect and identify aromatic and aliphatic lichen substances; it enabled quantitative analysis of substances having no or less absorption of ultraviolet rays such as triterpenoids. In addition, they can be measured in high accuracy compared with the TLC method.     

Tumor angiogenesis and molecular target therapy in ovarian carcinomas

Growth of solid tumors depends on angiogenesis, the process by which new blood vessels develop from the endothelium of a pre-existing vasculature. Tumors promote angiogenesis by secreting various angiogeneic factors, and newly formed blood vessels induce tumor cell proliferation and invasiveness. Ovarian carcinomas have a poor prognosis, often associated with multifocal intraperitoneal dissemination accompanied by intense neovascularization. The degree of angiogenesis of ovarian carcinomas may directly influence the clinical course of the disease. Although a growing body of evidence indicates that angiogenic intensity may play a prognostic role in gynecological malignancies including ovarian carcinomas, the related biological mechanisms remain to be further elucidated. In this review, we describe current knowledge pertaining to mechanisms and regulation of angiogenesis in ovarian carcinomas with special reference to our recent research results.     

JNK regulates the photic response of the mammalian circadian clock

The posttranslational regulation of mammalian clock proteins has been assigned a time-keeping function, but seems to have more essential roles. Here we show that c-Jun N-terminal kinase (JNK), identified by inhibitor screening of BMAL1 phosphorylation at Ser 520/Thr 527/Ser 592, confers dynamic regulation on the clock. Knockdown of JNK1 and JNK2 abrogates BMAL1 phosphorylation and lengthens circadian period in fibroblasts. Mice deficient for neuron-specific isoform JNK3 have altered behavioural rhythms, with longer free-running period and compromised phase shifts to light. The locomotor rhythms are insensitive to intensity variance of constant light, deviating from Aschoff's rule. Thus, JNK regulates a core characteristic of the circadian clock by controlling the oscillation speed and the phase in response to light.     

A dibenzoylmethane derivative protects dopaminergic neurons against both oxidative stress and endoplasmic reticulum stress

The enhancement of intracellular stresses such as oxidative stress and endoplasmic reticulum (ER) stress has been implicated in several neurodegenerative disorders including Parkinson's disease (PD). During a search for compounds that regulate ER stress, a dibenzoylmethane (DBM) derivative 14-26 (2,2'-dimethoxydibenzoylmethane) was identified as a novel neuroprotective agent. Analysis in SH-SY5Y cells and in PC12 cells revealed that the regulation of ER stress by 14-26 was associated with its anti-oxidative property. 14-26 prevented the production of reactive oxygen species (ROS) when the cells were exposed to oxidants such as hydrogen peroxide and 6-hydroxydopamine (6-OHDA) or an ER stressor brefeldin A (BFA). 14-26 also prevented ROS-induced damage in both the ER and the mitochondria, including the protein carbonylation in the microsome and the reduction of the mitochondrial membrane potential. Further examination disclosed the presence of the iron-chelating activity in 14-26. In vivo, 14-26 suppressed both oxidative stress and ER stress and prevented neuronal death in the substantia nigra pars compacta (SNpc) after injection of 6-OHDA in mice. These results suggest that 14-26 is an antioxidant that protects dopaminergic neurons against both oxidative stress and ER stress and could be a therapeutic candidate for the treatment of PD.