Para-Hydroxybenzyl Alcohol Delays the Progression of Neurodegenerative Diseases in Models of Caenorhabditis elegans through Activating Multiple Cellular Protective Pathways.

The traditional Chinese medicine Gastrodia elata (commonly called "Tianma" in Chinese) has been widely used in the treatment of rheumatism, epilepsy, paralysis, headache, and dizziness. Phenolic compounds, such as gastrodin, para-hydroxybenzyl alcohol (HBA), p-hydroxybenzaldehyde, and vanillin are the main bioactive components isolated from Gastrodia elata. These compounds not only are structurally related but also share similar pharmacological activities, such as antioxidative and anti-inflammatory activities, and effects on the treatment of aging-related diseases. Here, we investigated the effect of para-hydroxybenzyl alcohol (HBA) on neurodegenerative diseases and aging in models of Caenorhabditis elegans (C. elegans). Our results showed that HBA effectively delayed the progression of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease in models of C. elegans. In addition, HBA could increase the average lifespan of N2 worms by more than 25% and significantly improve the age-related physiological functions of worms. Moreover, HBA improved the survival rate of worms under stresses of oxidation, heat, and pathogenic bacteria. Further mechanistic investigation revealed that HBA could activate FOXO/DAF-16 and SKN-1 to regulate antioxidative and xenobiotic metabolism pathway. HBA could also activate HSF-1 to regulate proteostasis maintenance pathway, mitochondrial unfolded stress response, endoplasmic stress response and autophagy pathways. The above results suggest that HBA activated multiple cellular protective pathways to increase stress resistance and protect against aging and aging-related diseases. Overall, our study indicates that HBA is a potential candidate for future development of antiaging pharmaceutical application.

Clinical Relevance of Serum Selenium Levels and Abdominal Aortic Calcification.

Selenium (Se) is an essential micronutrient with antioxidative properties, but previous studies have shown that extremely high circulating Se concentrations are associated with a higher prevalence of cardiovascular diseases (CVDs). To date, it remains unknown whether this association has connections with arterial calcification. A total of 982 participants with both serum Se concentration and abdominal aortic calcification (AAC) score data were enrolled from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), a cross-sectional study of a noninstitutionalized population in the USA. Serum Se levels were determined by inductively coupled plasma-dynamic reaction cell-mass spectrometry. AAC was obtained from dual-energy X-ray absorptiometry and quantified by the Kauppila score system. Severe AAC was defined as Kauppila score ≥ 5. Among all participants, the mean serum Se level was 132.89 µg/L. The average AAC score was 1.51, and 11.7% had severe AAC. Compared with those in the lowest quartile of Se (< 121.1 µg/L), the highest quartile subgroup (> 143.1 µg/L) was associated with a higher mean AAC score (ß-coefficient 0.88; 95% CI 0.28, 1.47; p = 0.004) and greater odds of having severe AAC (odds ratio 2.19; 95% CI 1.10, 4.36; p = 0.026) after adjusting for demographic, biochemical, and clinical characteristics. The concentrations of other circulating trace elements showed no statistically significant association with the AAC score. High serum Se levels were independently associated with an increased mean AAC score and aggravated AAC severity among noninstitutionalized US adults. Serum Se might adversely affect the cardiovascular system when the serum Se concentration exceeds 143 µg/L.

Inositol polyphosphate multikinase IPMK-1 regulates development through IP3/calcium signaling in Caenorhabditis elegans.

Inositol polyphosphate multikinase (IPMK) is a conserved protein that initiates the production of inositol phosphate intracellular messengers and is critical for regulating a variety of cellular processes. Here, we report that the C. elegans IPMK-1, which is homologous to the mammalian inositol polyphosphate multikinase, plays a crucial role in regulating rhythmic behavior and development. The deletion mutant ipmk-1(tm2687) displays a long defecation cycle period and retarded postembryonic growth. The expression of functional ipmk-1::GFP was detected in the pharyngeal muscles, amphid sheath cells, the intestine, excretory (canal) cells, proximal gonad, and spermatheca. The expression of IPMK-1 in the intestine was sufficient for the wild-type phenotype. The IP3-kinase activity of IPMK-1 is required for defecation rhythms and postembryonic development. The defective phenotypes of ipmk-1(tm2687) could be rescued by a loss-of-function mutation in type I inositol 5-phosphatase homolog (IPP-5) and improved by a supplemental Ca2+ in the medium. Our work demonstrates that IPMK-1 and the signaling molecule inositol triphosphate (IP3) pathway modulate rhythmic behaviors and development by dynamically regulating the concentration of intracellular Ca2+ in C. elegans. Advances in understanding the molecular regulation of Ca2+ homeostasis and regulation of organism development may lead to therapeutic strategies that modulate Ca2+ signaling to enhance function and counteract disease processes. Unraveling the physiological role of IPMK and the underlying functional mechanism in C. elegans would contribute to understanding the role of IPMK in other species, especially in mammals, and benefit further research on the involvement of IPMK in disease.