Association Between Single Nucleotide Polymorphisms in PPARA and EPAS1 Genes and High-Altitude Appetite Loss in Chinese Young Men

Appetite loss is a common symptom that occurs in high altitude (HA) for lowlanders. Previous studies indicated that hypoxia is the initiating vital factor of HA appetite loss. PPARA, EPAS1, EGLN1, HIF1A, HIF1AN, and NFE2L2 play important roles in hypoxic responses. We aimed to explore the association of these hypoxia-related gene polymorphisms with HA appetite loss. In this study, we enrolled 416 young men who rapidly ascended to Lhasa (3700 m) from Chengdu (<500m) by plane. PPARA, EPAS1, EGLN1, HIF1A, HIF1AN, and NFE2L2 were genotyped by MassARRAY. Appetite scores were measured to identify HA appetite loss. Logistic regression and multiple genetic models were tested to evaluate the association between the single nucleotide polymorphisms (SNPs) and risk of HA appetite loss in crude and adjusted (age and SaO2) analysis. Subsequently, Haploview software was used to analyze the linkage disequilibrium (LD), haplotype construction and the association of diverse haplotypes with the risk of HA appetite loss. Our results revealed that allele “A” in PPARA rs4253747 was significantly associated with the increased risk of HA appetite loss. Codominant, dominant, recessive, and log-additive models of PPARA rs4253747 showed the increased risk of HA appetite loss in the crude and adjusted analysis. However, only dominant, overdominant, and log-additive models of EPAS1 rs6756667 showed decreased risk of HA appetite loss in the crude and adjusted analysis. Moreover, the results from haplotype-based test showed that the rs7292407-rs6520015 haplotype “AC” was associated with HA appetite loss in the crude analysis rather than the adjusted analysis. In this study, we first established the association of SNPs in PPARA (rs4253747) and EPAS1 (rs6756667) genes with susceptibility to HA appetite loss in Han Chinese young men. These findings provide novel insights into understanding the mechanisms involved in HA appetite loss

Ursolic-Acid-Enriched Herba Cynomorii Extract Protects against Oxidant Injury in H9c2 Cells and Rat Myocardium by Increasing Mitochondrial ATP Generation Capacity and Enhancing Cellular Glutathione Redox Cycling, Possibly through Mitochondrial Uncoupling

Mitochondrial decay is considered to be a major contributor to aging-related diseases, including neurodegenerative diseases, cardiovascular disorders, and certain metabolic diseases. Therefore, the maintenance of mitochondrial functional capacity and antioxidant status should play an essential role in preventive health. Herba Cynomorii, which is one of the most potent "Yang-invigorating" Chinese tonic herbs, was found to increase mitochondrial ATP generation capacity (ATP-GC) in rat hearts ex vivo. In the present study, we demonstrated that HCY2, an active fraction of Herba Cynomorii, and its major ingredient ursolic acid (UA) could protect against hypoxia/reoxygenation-induced cell apoptosis in H9c2 cells in vitro and also against ischemia/reperfusion-induced injury in rat hearts ex vivo. The cardioprotection was associated with an increase in ATP-GC and an enhancement of glutathione redox cycling. The results suggest that UA may be one of the active ingredients responsible for the cardioprotection afforded by Herba Cynomorii, and this effect may be mediated, at least in part, by enhancement of mitochondrial functional capacity and antioxidant status, possibly through the induction of mitochondrial uncoupling

Ursolic Acid-Enriched Herba Cynomorii Extract Induces Mitochondrial Uncoupling and Glutathione Redox Cycling Through Mitochondrial Reactive Oxygen Species Generation: Protection Against Menadione Cytotoxicity in H9c2 Cells

Herba Cynomorii (Cynomorium songaricum Rupr., Cynomoriaceae) is one of the most commonly used 'Yang-invigorating' tonic herbs in Traditional Chinese Medicine (TCM). An earlier study in our laboratory has demonstrated that HCY2, an ursolic acid-enriched fraction derived from Herba Cynomorii, increased mitochondrial ATP generation capacity (ATP-GC) and induced mitochondrial uncoupling as well as a cellular glutathione response, thereby protecting against oxidant injury in H9c2 cells. In this study, we demonstrated that pre-incubation of H9c2 cells with HCY2 increased mitochondrial reactive oxygen species (ROS) generation in these cells, which is likely an event secondary to the stimulation of the mitochondrial electron transport chain. The suppression of mitochondrial ROS by the antioxidant dimethylthiourea abrogated the HCY2-induced enhancement of mitochondrial uncoupling and glutathione reductase (GR)-mediated glutathione redox cycling, and also protected against menadione-induced cytotoxicity. Studies using specific inhibitors of uncoupling protein and GR suggested that the HCY2-induced mitochondrial uncoupling and glutathione redox cycling play a determining role in the cytoprotection against menadione-induced oxidant injury in H9c2 cells. Experimental evidence obtained thus far supports the causal role of HCY2-induced mitochondrial ROS production in eliciting mitochondrial uncoupling and glutathione antioxidant responses, which offer cytoprotection against oxidant injury in H9c2 cells

Predicting Positive and Negative Links in Signed Social Networks by Transfer Learning

Different from a large body of research on social networks that has focused almost exclusively on positive relationships, we study signed social networks with both positive and negative links. Specifically, we focus on how to reliably and effectively predict the signs of links in a newly formed signed social network (called a target network). Since usually only a very small amount of edge sign information is available in such newly formed networks, this small quantity is not adequate to train a good classifier. To address this challenge, we need assistance from an existing, mature signed network (called a source network) which has abundant edge sign information. We adopt the transfer learning approach to leverage the edge sign information from the source network, which may have a different yet related joint distribution of the edge instances and their class labels. As there is no predefined feature vector for the edge instances in a signed network, we construct generalizable features that can transfer the topological knowledge from the source network to the target. With the extracted features, we adopt an AdaBoost-like transfer learning algorithm with instance weighting to utilize more useful training instances in the source network for model learning. Experimental results on three real large signed social networks demonstrate that our transfer learning algorithm can improve the prediction accuracy by 40 % over baseline methods

Yang/Qi invigoration: An herbal therapy for chronic fatigue syndrome with yang deficiency?

According to traditional Chinese medicine (TCM) theory, Yang and Qi are driving forces of biological activities in the human body. Based on the crucial role of the mitochondrion in energy metabolism, we propose an extended view of Yang and Qi in the context of mitochondrion-driven cellular and body function. It is of interest that the clinical manifestations of Yang/Qi deficiencies in TCM resemble those of chronic fatigue syndrome in Western medicine, which is pathologically associated with mitochondrial dysfunction. By virtue of their ability to enhance mitochondrial function and its regulation, Yang- and Qi-invigorating tonic herbs, such as Cistanches Herba and Schisandrae Fructus, may therefore prove to be beneficial in the treatment of chronic fatigue syndrome with Yang deficiency