In this paper, the therapeutic mechanism of R rosea for AMS was investigated by analysis of the relationship between R rosea compositions and hypoxia-inducible factor 1 (HIF-1) degradation pathway.System biology and network biology, computational approaches were used to explore the molecular mechanisms of traditional Chinese medicine (TCM).Our results showed that chemical compositions of R rosea could inhibit the targets of HIF-1 degradation pathway in multi-composition/multi-target ways.We conclude that the 18 components with more than 2 targets and 5 targets (arrest-defective-1 [ARD1], forkhead transcription factor [FOXO4], osteosarcoma-9 [OS-9], prolyl hydroxylase 2 [PHD2], human double minute 2 [Hdm2]) deserve to be noticed, and PHD2, receptor for activated C-kinase1 (RACK1) and spermidine/spermine-N1-acetyltransferase-1 (SSAT1) may be the targets of active ingredients of rhodionin, rhodiosin, and rhodiolatuntoside, respectively.
The occurrence of acute mountain sickness (AMS), which develops in some individuals who ascend to altitudes above 2,500 m, may be associated with 4 hypoxia-related genes (HIF-1, VEGFA, HSP-70 and eNOS).
Though increased HIF-1α expression is associated with adaptation and protection from AMS development in the early stage of hypoxia, a downstream effector of HIF-1α, VEGF, can induce overzealous endothelial barrier dysfunction, increase vascular permeability, and ultimately result in HAPE and high-altitude cerebral edema.
The aim of this study was to investigate the associations between alleles of the hypoxia-inducible factor 1A (HIF1A) C1772T polymorphism and several physiological responses to hypoxia, including the hypoxic ventilatory response (HVR), and serum erythropoietin (EPO), arterial oxygen saturation (Sao2), and acute mountain sickness (AMS) responses during 8 hours of exposure to normobaric hypoxia.
Two low oxygen sensors, Egl nine homolog 1 (EGLN1) and hypoxia-inducible factor 1-α inhibitor (HIF-1AN), play pivotal roles in the regulation of HIF-1α, and high altitude adaption may be involved in the pathology of acute mountain sickness (AMS).
Thus, ACE I/D genotype is associated with successful high altitude ascent in this prospective study-an association not explicable by genotype-dependence of AMS onset or severity.
The rs3025039 SNP and the haplotype (rs1413711, rs833070 and rs3025000) in the VEGFA gene were significantly associated with AMS (p = 0.0435 and 0.024, respectively).
In this paper, the therapeutic mechanism of R rosea for AMS was investigated by analysis of the relationship between R rosea compositions and hypoxia-inducible factor 1 (HIF-1) degradation pathway.System biology and network biology, computational approaches were used to explore the molecular mechanisms of traditional Chinese medicine (TCM).Our results showed that chemical compositions of R rosea could inhibit the targets of HIF-1 degradation pathway in multi-composition/multi-target ways.We conclude that the 18 components with more than 2 targets and 5 targets (arrest-defective-1 [ARD1], forkhead transcription factor [FOXO4], osteosarcoma-9 [OS-9], prolyl hydroxylase 2 [PHD2], human double minute 2 [Hdm2]) deserve to be noticed, and PHD2, receptor for activated C-kinase1 (RACK1) and spermidine/spermine-N1-acetyltransferase-1 (SSAT1) may be the targets of active ingredients of rhodionin, rhodiosin, and rhodiolatuntoside, respectively.
In this paper, the therapeutic mechanism of R rosea for AMS was investigated by analysis of the relationship between R rosea compositions and hypoxia-inducible factor 1 (HIF-1) degradation pathway.System biology and network biology, computational approaches were used to explore the molecular mechanisms of traditional Chinese medicine (TCM).Our results showed that chemical compositions of R rosea could inhibit the targets of HIF-1 degradation pathway in multi-composition/multi-target ways.We conclude that the 18 components with more than 2 targets and 5 targets (arrest-defective-1 [ARD1], forkhead transcription factor [FOXO4], osteosarcoma-9 [OS-9], prolyl hydroxylase 2 [PHD2], human double minute 2 [Hdm2]) deserve to be noticed, and PHD2, receptor for activated C-kinase1 (RACK1) and spermidine/spermine-N1-acetyltransferase-1 (SSAT1) may be the targets of active ingredients of rhodionin, rhodiosin, and rhodiolatuntoside, respectively.
Plasma VEGF at 14, 200 feet for subjects with AMS (62 +/- 12 pg/mL; n = 15) did not differ significantly from subjects at 14,200 feet without AMS, or from control subjects at sea level.
The occurrence of acute mountain sickness (AMS), which develops in some individuals who ascend to altitudes above 2,500 m, may be associated with 4 hypoxia-related genes (HIF-1, VEGFA, HSP-70 and eNOS).
To assess the association between EGLN1 and HIF-1AN SNPs and AMS in a Han Chinese population, a case-control study was performed including 190 patients and 190 controls.
The aim of this study was to investigate the associations between alleles of the hypoxia-inducible factor 1A (HIF1A) C1772T polymorphism and several physiological responses to hypoxia, including the hypoxic ventilatory response (HVR), and serum erythropoietin (EPO), arterial oxygen saturation (Sao2), and acute mountain sickness (AMS) responses during 8 hours of exposure to normobaric hypoxia.
Age was found to be significantly associated with the EPAS1 SNP in the CMS patients while heart rate (HR) and oxygen saturation level of hemoglobin (SaO(2)) were found to be significantly associated with the EGLN1 (rs480902) SNP in the Han patients with AMS.
We tested the hypothesis that haplotypes, as determined by tagSNPs, in NOS3 would be differentially represented in individuals with and without AMS sampled at the Janai Purnima Festival at Lake Gosain Kunda, Nepal, at 4380 m. Seven SNPs were tested, and a highly significant association (p = 0.004) was found for genotypes of the commonly studied missense polymorphism Glu298Asp (rs 1799983; G/T transversion at base 894).
The rs4953348 polymorphism of EPAS1 gene had a significant correlation with the SaO2 level and AMS, and a significant difference in the AG and GG genotype distribution between the AMS and non-AMS groups.