Dauer pheromones or daumones, which are signaling molecules that interrupt development and reproduction (dauer larvae) during unfavorable growth conditions, are essential for cellular homeostasis in Caenorhabditis elegans. According to earlier studies, dauer larva formation in strain N2 is enhanced by a temperature increase, suggesting the involvement of a temperature-dependent component in dauer pheromone biosynthesis or sensing. Several naturally occurring daumone analogs (e.g. daumones 1-3) have been identified, and these molecules are predicted to be synthesized in different physiological settings in this nematode. To elucidate the molecular regulatory system that may influence the dynamic balance of specific daumone production in response to sudden temperature changes, we characterized the peroxisomal acox gene encoding acyl-CoA oxidase, which is predicted to catalyze the first reaction during biosynthesis of the fatty acid component of daumones. Using acox-1(ok2257) mutants and a new, robust analytical method, we quantified the three most abundant daumones in worm bodies and showed that acox likely contributes to the dynamic production of various quantities of three different daumones in response to temperature increase, changes that are critical in C. elegans for coping with the natural environmental changes it faces.

The nematode worm Caenorhabditis elegans survives by adapting to environmental stresses such as temperature extremes by increasing the concentrations of ascaroside pheromones, termed ascarosides or daumones, which signal early C. elegans larvae to enter a non-aging dauer state for long-term survival. It is well known that production of ascarosides is stimulated by heat stress, resulting in enhanced dauer formation by which worms can adapt to environmental insults. However, the molecular mechanism by which ascaroside pheromone biosynthesis is stimulated by heat stress remains largely unknown. In the present study, we show that the heat-shock transcription factor HSF-1 can mediate enhanced ascaroside pheromone biosynthesis in response to heat stress by activating the peroxisomal fatty acid β-oxidation genes in C. elegans. To explore the potential molecular mechanisms, we examined the four major genes involved in the ascaroside biosynthesis pathway and then quantified the changes in both the expression of these genes and ascaroside production under heat-stress conditions. The transcriptional activation of ascaroside pheromone biosynthesis genes by HSF-1 was quite notable, which is not only supported by chromatin immunoprecipitation assays, but also accompanied by the enhanced production of chemically detectable major ascarosides (e.g. daumones 1 and 3). Consequently, the dauer formation rate was significantly increased by the ascaroside pheromone extracts from N2 wild-type but not from hsf-1(sy441) mutant animals grown under heat-stress conditions. Hence heat-stress-enhanced ascaroside production appears to be mediated at least in part by HSF-1, which seems to be important in adaptation strategies for coping with heat stress in this nematode.

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Background/Aims: Biphenyl dimethyl dicarboxylate (DDB) combined with garlic oil (pennel) has been used to treat chronic liver disease. A randomized, double-blind, active-and placebo-controlled clinical trial was conducted to investigate the efficacy, safety and quality of life in chronic liver disease patients. Methods: A total of 237 patients with chronic liver disease were randomized into three groups; 100 patients were administered pennel, 102 patients Legalon as an active-control and 35 patients placebo for 12 weeks. The primary endpoint was the rate of alanine aminotransferase (ALT) normalization. We assessed differences in ALT levels and malondialdehyde (MDA) as an oxidative biomarker between 0 and 12 weeks, the improvement in quality of life using a chronic liver disease questionnaire (CLDQ) and the incidence of adverse events.