Preliminary study of identified novel susceptibility loci for HAPE risk in a Chinese male Han population.

High altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic pulmonary edema. In recent years, association studies have become the main method for identifying HAPE genetic loci. A genome-wide association study (GWAS) of HAPE risk-associated loci was performed in Chinese male Han individuals (164 HAPE cases and 189 healthy controls) by the Precision Medicine Diversity Array Chip with 2,771,835 loci (Applied Biosystems Axiom™). Eight overlapping candidate loci in CCNG2, RP11-445O3.2, NUPL1 and WWOX were finally selected. In silico functional analyses displayed the PPI network, functional enrichment and signal pathways related to CCNG2, NUPL1, WWOX and NRXN1. This study provides data supplements for HAPE susceptibility gene loci and new insights into HAPE susceptibility.

Network pharmacology prediction, molecular docking and in vitro experiment explored the potential mechanism of Gaoyuan'an capsule in improving hypoxia tolerance.

BACKGROUND: Tibetan medicine Gaoyuan'an capsule (GYAC) is widely used to prevent pulmonary edema at high altitude, but the specific mechanism has not been explored. In this study, we analyzed the mechanism of GYAC in hypoxia tolerance, and provided a new idea for the prevention and treatment of altitude disease. METHODS: The effective components and corresponding targets of GYAC were screened out by the Chinese herbal medicine network database, and the key targets of hypoxia tolerance were retrieved by Genecards, OMIM and PubMed database. Cytoscape 3.7.2 was used to construct GYAC ingredient-target-hypoxia tolerance-related target network. GO function annotation and KEGG enrichment analysis were performed to predict the pathways in which target genes may be involved, and molecular docking was used to verify the binding ability of the compound to target genes. In vitro, the above results were further verified by molecular experiment. RESULTS: We found that GYAC can improve hypoxia tolerance by regulating various target genes, including IL6, IFNG, etc. The main regulatory pathways were HIF-1 signaling pathway. Molecular docking showed that the affinity between luteolin and target genes (IL6, IFNG) were better. In vitro, we observed that hypoxia can inhibit cell viability and promote apoptosis of H9C2 cell. And hypoxia can promote the expression of LDH. After the addition of luteolin, the decrease of cell viability, the increase of cell apoptosis, LDH release and the decrease of mitochondrial membrane potential were inhibited. Besides, inflammatory related factors (IL-6, IL-10, IL-2, IFNG and VEGFA) expression were also inhibited hypoxic cell models. CONCLUSIONS: The results of network pharmacology and molecular docking showed that luteolin, a monomeric component of GYAC, played a role in hypoxia tolerance through a variety of target genes, such as IL6, IFNG. What's more, we have discovered that luteolin can reduce the inflammatory response in cardiac myocytes, thereby alleviating mitochondrial damage, and ultimately enhancing the hypoxia tolerance of H9C2 cardiomyocytes.

Long noncoding RNA ANRIL alleviates hypoxia-induced pulmonary microvascular endothelial cell damage.

BACKGROUND: High-altitude pulmonary oedema (HAPE) is a form of noncardiogenic pulmonary oedema. Studies have found that long noncoding RNA (lncRNA) plays an important role in HAPE. ANRIL is significant in pulmonary illnesses, which implies that alterations in ANRIL expression levels may be involved in the beginning and development of HAPE. However, the specific mechanism is indistinct. The present study is meant to explore the effect and mechanism of ANRIL on hypoxic-induced injury of pulmonary microvascular endothelial cells (PMEVCs). METHODS: In the hypoxic model of PMVECs, overexpression of ANRIL or knockdown of miR-181c-5p was performed to assess cell proliferation, apoptosis, and migration. Furthermore, the levels of apoptosis-related proteins, inflammatory factors, and vascular active factors were also measured. RESULTS: The results showed that, after 24 h of hypoxia, PMVECs proliferation and migration were suppressed in comparison to the control group, along with an increase in apoptosis, a decrease in the expression of ANRIL, and an increase in the expression of miR-181c-5p (all p < .05). The damage caused by hypoxia in PMVECs can be lessened by overexpressing ANRIL, which also inhibits the production of TNF-α, iNOS, and VEGF as well as BAX and cleaved caspase-3 (all p < .05). Further experimental results showed that overexpression of ANRIL and knockdown of miR-181c-5p had the same protection against hypoxic injury in PMVECs (all p < .05). CONCLUSIONS: Our study suggests that ANRIL may prevent hypoxia injury to PMVECs in HAPE through the negative regulation of miR-181c-5p.

Whole-exome sequencing in searching for novel variants associated with the development of high altitude pulmonary edema.

BACKGROUND: High altitude pulmonary edema (HAPE) is a high-altitude idiopathic disease with serious consequences due to hypoxia at high altitude, and there is individual genetic susceptibility. Whole-exome sequencing (WES) is an effective tool for studying the genetic etiology of HAPE and can identify potentially novel mutations that may cause protein instability and may contribute to the development of HAPE. MATERIALS AND METHODS: A total of 50 unrelated HAPE patients were examined using WES, and the available bioinformatics tools were used to perform an analysis of exonic regions. Using the Phenolyzer program, disease candidate gene analysis was carried out. SIFT, PolyPhen-2, Mutation Taster, CADD, DANN, and I-Mutant software were used to assess the effects of genetic variations on protein function. RESULTS: The results showed that rs368502694 (p. R1022Q) located in NOS3, rs1595850639 (p. G61S) located in MYBPC3, and rs1367895529 (p. R333H) located in ITGAV were correlated with a high risk of HAPE, and thus could be regarded as potential genetic variations associated with HAPE. CONCLUSION: WES was used in this study for the first time to directly screen genetic variations related to HAPE. Notably, our study offers fresh information for the subsequent investigation into the etiology of HAPE.

Temporal and spatial discrepancies of VOCs in an industrial-dominant city in China during summertime.

Ozone (O3) pollution is currently problematic to cities across the globe. Many non-methane hydrocarbons (NMHCs) are efficient O3 precursors. In this study, target volatile organic compounds (VOCs), including oxygenated VOCs (known as carbonyls), were monitored at eight sampling sites distributed in urban and suburban in the typical and industrial-dominant city of Shaoxing, Zhejiang province, China. At the suburban sites, C8-C12 alkanes, aromatics with lower reactivity (kOH <13 × 10-12 cm3 mol-1 s-1) and acetonitrile were more abundant than urban ones due to higher emissions from diesel-fueled trucks and biomass burning. In general, higher abundances of total quantified NMHCs (ΣNMHC) were found on high O3 (HO) days. The increments of formaldehyde (C1) and O3 were higher in urban than suburban, while a reverse trend was seen for acetaldehyde (C2). Substantial and local biogenic inputs of C2 were found in suburban in the afternoon when both temperature and light intensity reached maximum of the day. In urban, higher increment was found for O3 than the carbonyls, representing that the secondary formation of O3 was more efficient. Distance decay gradient of most representative NMHCs were positively correlated to the distances from a westernmost industrial origin located at the upwind location. The net loss rates of the NMHCs ranged from -0.009 to -0.11 ppbv km-1, while the higher rates were seen for the most reactive species like C2-C4 alkenes. The results and interpretation of this study are informative to establish efficient local control measures for O3 and the related percussors for the microscale industrial cities in China.

[Emission Characteristics and Risk Assessment of Volatile Organic Compounds from Typical Factories in Zhengzhou].

To understand the characteristics and potential hazards of volatile organic compounds (VOCs) emitted from different industrial factories in Zhengzhou, several representative factories have been selected for sample collection using canisters; the samples were subsequently analyzed by GC-MS/FID system, from which the composition and risk of VOCs are discussed in this study. It was found that OVOCs, especially ethyl acetate and isopropanol, were the most important species originating from printing factories, which accounted for more than 93.1% of total VOCs. The major components related to manufacturing industries, including automobile, furniture, and coating, were aromatics, mainly m/p-xylene, o-xylene, and ethylbenzene, which contributed 33.5%-90.0% to VOCs. Halogenated hydrocarbons made the largest contribution (52.3%) to VOCs in the food processing industry. The main components of VOCs were halogenoalkanes (25.5%) and alkanes (28.8%) in rubber factories. As for graphite carbon factories, the main components of VOCs were aromatics (28.5%) and alkanes (24.1%). Compared with previous studies, the VOC emission characteristics of factories involving solvent usage in Zhengzhou are consistent with those in other cities, but the compositional information of VOCs varies across different factories, even within the same industry, due to the different production processes and raw materials used. Risk assessment showed that the concentration of VOCs emitted from solvent factories are positively correlated with ozone formation potential (OFP) and the hazard index (HI). Specifically, benzene, toluene, ethylbenzene, xylene, and other C6-C8 aromatic hydrocarbons contributed significantly to OFP and HI. The HI values were 1.18 and 2.74 in automobile manufacturing factory NO.3 and wooden furniture factory NO.5, respectively, which were higher than the limits stated by EPA regulations because of the different production processes and raw materials, and the VOCs of the factories were mainly composed of aromatics; in particular, C6-C9 benzene series contributed significantly to HI and OFP. Therefore, it is necessary to control VOCs originating from industries involving solvent usage.