Phenomics (Cham, Switzerland)最新文献

{"title":"Deep Learning-Assisted Quantitative Susceptibility Mapping as a Tool for Grading and Molecular Subtyping of Gliomas.","authors":"Wenting Rui, Shengjie Zhang, Huidong Shi, Yaru Sheng, Fengping Zhu, YiDi Yao, Xiang Chen, Haixia Cheng, Yong Zhang, Ababikere Aili, Zhenwei Yao, Xiao-Yong Zhang, Yan Ren","doi":"10.1007/s43657-022-00087-6","DOIUrl":"10.1007/s43657-022-00087-6","url":null,"abstract":"<p><p>This study aimed to explore the value of deep learning (DL)-assisted quantitative susceptibility mapping (QSM) in glioma grading and molecular subtyping. Forty-two patients with gliomas, who underwent preoperative T2 fluid-attenuated inversion recovery (T2 FLAIR), contrast-enhanced T1-weighted imaging (T1WI + C), and QSM scanning at 3.0T magnetic resonance imaging (MRI) were included in this study. Histopathology and immunohistochemistry staining were used to determine glioma grades, and <i>isocitrate dehydrogenase</i> (<i>IDH</i>) <i>1 </i>and <i>alpha thalassemia/mental retardation syndrome X-linked gene</i> (<i>ATRX</i>) subtypes. Tumor segmentation was performed manually using Insight Toolkit-SNAP program (www.itksnap.org). An inception convolutional neural network (CNN) with a subsequent linear layer was employed as the training encoder to capture multi-scale features from MRI slices. Fivefold cross-validation was utilized as the training strategy (seven samples for each fold), and the ratio of sample size of the training, validation, and test dataset was 4:1:1. The performance was evaluated by the accuracy and area under the curve (AUC). With the inception CNN, single modal of QSM showed better performance in differentiating glioblastomas (GBM) and other grade gliomas (OGG, grade II-III), and predicting <i>IDH1</i> mutation and <i>ATRX</i> loss (accuracy: 0.80, 0.77, 0.60) than either T2 FLAIR (0.69, 0.57, 0.54) or T1WI + C (0.74, 0.57, 0.46). When combining three modalities, compared with any single modality, the best AUC/accuracy/F1-scores were reached in grading gliomas (OGG and GBM: 0.91/0.89/0.87, low-grade and high-grade gliomas: 0.83/0.86/0.81), predicting <i>IDH1</i> mutation (0.88/0.89/0.85), and predicting <i>ATRX</i> loss (0.78/0.71/0.67). As a supplement to conventional MRI, DL-assisted QSM is a promising molecular imaging method to evaluate glioma grades, <i>IDH1</i> mutation, and <i>ATRX</i> loss.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-022-00087-6.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 3","pages":"243-254"},"PeriodicalIF":0.0,"publicationDate":"2023-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9661057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infrared Imageries of Human Body Activated by Tea Match the Hypothesis of Meridian System.","authors":"Wenli Jin, Yichen Tao, Chen Wang, Lufei Wang, Xue Ao, Mingjie Su, Binwei Hu, Yuxiao Ouyang, Jiaxing Liu, Hui Li","doi":"10.1007/s43657-022-00090-x","DOIUrl":"10.1007/s43657-022-00090-x","url":null,"abstract":"<p><p>Human meridian (<i>Jingluo</i>) system was hypothesized by traditional Chinese medicine (TCM) for thousands of years, suggesting 12 normal meridian channels going through respective organs, carrying fluid and energy, and laying thermal effects. Some treatments based on meridians have been proved effective. However, existence of meridians has never been confirmed, let alone the lack of measurement for meridian phenotypes. Thermal effect is one of the major phenotypes of meridian metabolism. Infrared photograph was employed to display the picture of meridians since 1970. Unfortunately, no satisfactory results have been obtained. It is possible that only when a certain meridian is activated will there be thermal effect for successful infrared photograph. In this study, 13 types of tea were selected out of the herbs to activate the hypothesized 12 meridians for imagery taking. Forty-two volunteers took part in the experiment lasted for 13 days. Different tea was tested in different day. Infrared imageries of the human bodies were taken immediately after each tea was drunk. The highest temperatures of the fingers, palms, and above the organs were derived from the imageries and analyzed. The temperatures of the organs and fingers possibly connected by 12 hypothesized meridians rose together significantly following the meridian hypothesis. Infrared imageries showed quite clear shapes of the organs activated by different kinds of tea, e.g., heart and kidneys by yellow tea, etc. Some high temperature lines also matched the hypothetic meridians. Our work displayed the probable imageries of all the 12 hypothetic meridians for the first time, and proved with data that different foods may activate different organs following the meridian hypothesis, shedding light on a possible new method of targeted drug designs. Measurements of meridian phenotypes can be developed based on this method of activation.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-022-00090-x.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 5","pages":"502-518"},"PeriodicalIF":3.7,"publicationDate":"2023-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50164011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Portrait of Human Lymphoma Reveals Protein Molecular Fingerprint of Disease Specific Subtypes and Progression.","authors":"Xin Ku, Jinghan Wang, Haikuo Li, Chen Meng, Fang Yu, Wenjuan Yu, Zhongqi Li, Ziqi Zhou, Can Zhang, Ying Hua, Wei Yan, Jie Jin","doi":"10.1007/s43657-022-00075-w","DOIUrl":"10.1007/s43657-022-00075-w","url":null,"abstract":"<p><p>An altered proteome in lymph nodes often suggests abnormal signaling pathways that may be associated with diverse lymphatic disorders. Current clinical biomarkers for histological classification of lymphomas have encountered many discrepancies, particularly for borderline cases. Therefore, we launched a comprehensive proteomic study aimed to establish a proteomic landscape of patients with various lymphatic disorders and identify proteomic variations associated with different disease subgroups. In this study, 109 fresh-frozen lymph node tissues from patients with various lymphatic disorders (with a focus on Non-Hodgkin's Lymphoma) were analyzed by data-independent acquisition mass spectrometry. A quantitative proteomic landscape was comprehensively characterized, leading to the identification of featured protein profiles for each subgroup. Potential correlations between clinical outcomes and expression profiles of signature proteins were also probed. Two representative signature proteins, phospholipid-binding proteins Annexin A6 (ANXA6) and Phospholipase C Gamma 2 (PLCG2), were successfully validated via immunohistochemistry. We also evaluated the capability of acquired proteomic signatures to segregate multiple lymphatic abnormalities and identified several core signature proteins, such as Sialic Acid Binding Ig Like Lectin 1 (SIGLEC1) and GTPase of immunity-associated protein 5 (GIMAP5). In summary, the established lympho-specific data resource provides a comprehensive map of protein expression in lymph nodes during multiple disease states, thus extending the existing human tissue proteome atlas. Our findings will be of great value in exploring protein expression and regulation underlying lymphatic malignancies, while also providing novel protein candidates to classify various lymphomas for more precise medical practice.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-022-00075-w.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 2","pages":"148-166"},"PeriodicalIF":3.7,"publicationDate":"2022-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9489238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico Pipeline to Identify Tumor-Specific Antigens for Cancer Immunotherapy Using Exome Sequencing Data.","authors":"Diego Morazán-Fernández, Javier Mora, Jose Arturo Molina-Mora","doi":"10.1007/s43657-022-00084-9","DOIUrl":"10.1007/s43657-022-00084-9","url":null,"abstract":"<p><p>Tumor-specific antigens or neoantigens are peptides that are expressed only in cancer cells and not in healthy cells. Some of these molecules can induce an immune response, and therefore, their use in immunotherapeutic strategies based on cancer vaccines has been extensively explored. Studies based on these approaches have been triggered by the current high-throughput DNA sequencing technologies. However, there is no universal nor straightforward bioinformatic protocol to discover neoantigens using DNA sequencing data. Thus, we propose a bioinformatic protocol to detect tumor-specific antigens associated with single nucleotide variants (SNVs) or \"mutations\" in tumoral tissues. For this purpose, we used publicly available data to build our model, including exome sequencing data from colorectal cancer and healthy cells obtained from a single case, as well as frequent human leukocyte antigen (HLA) class I alleles in a specific population. HLA data from Costa Rican Central Valley population was selected as an example. The strategy included three main steps: (1) pre-processing of sequencing data; (2) variant calling analysis to detect tumor-specific SNVs in comparison with healthy tissue; and (3) prediction and characterization of peptides (protein fragments, the tumor-specific antigens) derived from the variants, in the context of their affinity with frequent alleles of the selected population. In our model data, we found 28 non-silent SNVs, present in 17 genes in chromosome one. The protocol yielded 23 strong binders peptides derived from the SNVs for frequent HLA class I alleles for the Costa Rican population. Although the analyses were performed as an example to implement the pipeline, to our knowledge, this is the first study of an in silico cancer vaccine using DNA sequencing data in the context of the HLA alleles. It is concluded that the standardized protocol was not only able to identify neoantigens in a specific but also provides a complete pipeline for the eventual design of cancer vaccines using the best bioinformatic practices.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-022-00084-9.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 2","pages":"130-137"},"PeriodicalIF":0.0,"publicationDate":"2022-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9541777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Genome-Wide Association Study for Susceptibility to Axial Length in Highly Myopic Eyes.","authors":"Qiang Lu, Yu Du, Ye Zhang, Yuxi Chen, Hao Li, Wenwen He, Yating Tang, Zhennan Zhao, Yinglei Zhang, Jihong Wu, Xiangjia Zhu, Yi Lu","doi":"10.1007/s43657-022-00082-x","DOIUrl":"10.1007/s43657-022-00082-x","url":null,"abstract":"<p><p>High myopia has long been highly prevalent worldwide with a largely yet unexplained genetic contribution. To identify novel susceptibility genes for axial length (AL) in highly myopic eyes, a genome-wide association study (GWAS) was performed using the genomic dataset of 350 deep whole-genome sequencing data from highly myopic patients. Top single nucleotide polymorphisms (SNPs) were functionally annotated. Immunofluorescence staining, quantitative polymerase chain reaction, and western blot were performed using neural retina of form-deprived myopic mice. Enrichment analyses were further performed. We identified the four top SNPs and found that <i>ADAM Metallopeptidase With Thrombospondin Type 1 Motif 16</i> (<i>ADAMTS16</i>) and <i>Phosphatidylinositol Glycan Anchor Biosynthesis Class Z</i> (<i>PIGZ</i>) had the potential of clinical significance. Animal experiments confirmed that PIGZ expression could be observed and showed higher expression level in form-deprived mice, especially in the ganglion cell layer. The messenger RNA (mRNA) levels of both <i>ADAMTS16</i> and <i>PIGZ</i> were significantly higher in the neural retina of form-deprived eyes (<i>p</i> = 0.005 and 0.007 respectively), and both proteins showed significantly upregulated expression in the neural retina of deprived eyes (<i>p</i> = 0.004 and 0.042, respectively). Enrichment analysis revealed a significant role of cellular adhesion and signal transduction in AL, and also several AL-related pathways including circadian entrainment and inflammatory mediator regulation of transient receptor potential channels were proposed. In conclusion, the current study identified four novel SNPs associated with AL in highly myopic eyes and confirmed that the expression of ADAMTS16 and PIGZ was significantly upregulated in neural retina of deprived eyes. Enrichment analyses provided novel insight into the etiology of high myopia and opened avenues for future research interest.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-022-00082-x.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 3","pages":"255-267"},"PeriodicalIF":0.0,"publicationDate":"2022-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9661059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurement of Cerebral Oxygen Extraction Fraction Using Quantitative BOLD Approach: A Review.","authors":"Hongwei Li, Chengyan Wang, Xuchen Yu, Yu Luo, He Wang","doi":"10.1007/s43657-022-00081-y","DOIUrl":"10.1007/s43657-022-00081-y","url":null,"abstract":"<p><p>Quantification of brain oxygenation and metabolism, both of which are indicators of the level of brain activity, plays a vital role in understanding the cerebral perfusion and the pathophysiology of brain disorders. Magnetic resonance imaging (MRI), a widely used clinical imaging technique, which is very sensitive to magnetic susceptibility, has the possibility of substituting positron emission tomography (PET) in measuring oxygen metabolism. This review mainly focuses on the quantitative blood oxygenation level-dependent (qBOLD) method for the evaluation of oxygen extraction fraction (OEF) in the brain. Here, we review the theoretic basis of qBOLD, as well as existing acquisition and quantification methods. Some published clinical studies are also presented, and the pros and cons of qBOLD method are discussed as well.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 1","pages":"101-118"},"PeriodicalIF":0.0,"publicationDate":"2022-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9201566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin Microbiome, Metabolome and Skin Phenome, from the Perspectives of Skin as an Ecosystem.","authors":"Huizhen Chen,&nbsp;Qi Zhao,&nbsp;Qian Zhong,&nbsp;Cheng Duan,&nbsp;Jean Krutmann,&nbsp;Jiucun Wang,&nbsp;Jingjing Xia","doi":"10.1007/s43657-022-00073-y","DOIUrl":"https://doi.org/10.1007/s43657-022-00073-y","url":null,"abstract":"<p><p>Skin is a complex ecosystem colonized by millions of microorganisms, including bacteria, fungi, and viruses. Skin microbiota is believed to exert critical functions in maintaining host skin health. Profiling the structure of skin microbial community is the first step to overview the ecosystem. However, the community composition is highly individualized and extremely complex. To explore the fundamental factors driving the complexity of the ecosystem, namely the selection pressures, we review the present studies on skin microbiome from the perspectives of ecology. This review summarizes the following: (1) the composition of substances/nutrients in the cutaneous ecological environment that are derived from the host and the environment, highlighting their proposed function on skin microbiota; (2) the features of dominant skin commensals to occupy ecological niches, through self-adaptation and microbe-microbe interactions; (3) how skin microbes, by their structures or bioactive molecules, reshape host skin phenotypes, including skin immunity, maintenance of skin physiology such as pH and hydration, ultraviolet (UV) protection, odor production, and wound healing. This review aims to re-examine the host-microbe interactions from the ecological perspectives and hopefully to give new inspiration to this field.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"2 6","pages":"363-382"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9201569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagic Clearance of Lipid Droplets Alters Metabolic Phenotypes in a Genetic Obesity-Diabetes Mouse Model.","authors":"Ningxie Chen,&nbsp;Boxun Lu,&nbsp;Yuhua Fu","doi":"10.1007/s43657-022-00080-z","DOIUrl":"10.1007/s43657-022-00080-z","url":null,"abstract":"<p><p>Lipid droplets (LDs) are intracellular organelles that store neutral lipids, and their aberrant accumulation is associated with many diseases including metabolic disorders such as obesity and diabetes. Meanwhile, the potential pathological contributions of LDs in these diseases are unclear, likely due to a lack of chemical biology tools to clear LDs. We recently developed LD-clearance small molecule compounds, Lipid Droplets·AuTophagy TEthering Compounds (LD·ATTECs), that are able to induce autophagic clearance of LDs in cells and in the liver of <i>db/db</i> (C57BL/6J Lepr^db/Lepr^db) mouse model, which is a widely used genetic model for obesity-diabetes. Meanwhile, the potential effects on the metabolic phenotype remain to be elucidated. Here, using the metabolic cage assay and the blood glucose assay, we performed phenotypic characterization of the effects of the autophagic degradation of LDs by LD·ATTECs in the <i>db/db</i> mouse model. The study reveals that LD·ATTECs increased the oxygen uptake of mice and the release of carbon dioxide, enhanced the heat production of animals, partially enhanced the exercise during the dark phase, decreased the blood glucose level and improved insulin sensitivity. Collectively, the study characterized the metabolic phenotypes induced by LD·ATTECs in an obesity-diabetes mouse model, revealing novel functional impacts of autophagic clearance of LDs and providing insights into LD biology and obesity-diabetes pathogenesis from the phenotypic perspective.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 2","pages":"119-129"},"PeriodicalIF":0.0,"publicationDate":"2022-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10110819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9489237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Meta-Analysis of the Genome-Wide Association Studies on Two Genetically Correlated Phenotypes Suggests Four New Risk Loci for Headaches.","authors":"Weihua Meng, Parminder S Reel, Charvi Nangia, Aravind Lathika Rajendrakumar, Harry L Hebert, Qian Guo, Mark J Adams, Hua Zheng, Zen Haut Lu, Debashree Ray, Lesley A Colvin, Colin N A Palmer, Andrew M McIntosh, Blair H Smith","doi":"10.1007/s43657-022-00078-7","DOIUrl":"10.1007/s43657-022-00078-7","url":null,"abstract":"<p><p>Headache is one of the commonest complaints that doctors need to address in clinical settings. The genetic mechanisms of different types of headache are not well understood while it has been suggested that self-reported headache and self-reported migraine were genetically correlated. In this study, we performed a meta-analysis of genome-wide association studies (GWAS) on the self-reported headache phenotype from the UK Biobank and the self-reported migraine phenotype from the 23andMe using the Unified Score-based Association Test (metaUSAT) software for genetically correlated phenotypes (<i>N</i> = 397,385). We identified 38 loci for headaches, of which 34 loci have been reported before and four loci were newly suggested. The <i>LDL receptor related protein 1</i> (<i>LRP1</i>)-<i>Signal Transducer and Activator of Transcription 6</i> (<i>STAT6</i>)-<i>S</i> <i>hort chain</i> <i>D</i> <i>ehydrogenase</i>/<i>R</i> <i>eductase family 9C member 7</i> (<i>SDR9C7</i>) region in chromosome 12 was the most significantly associated locus with a leading <i>p</i> value of 1.24 × 10^-62 of rs11172113. The <i>One Cut homeobox 2</i> (<i>ONECUT2</i>) gene locus in chromosome 18 was the strongest signal among the four new loci with a <i>p</i> value of 1.29 × 10^-9 of rs673939. Our study demonstrated that the genetically correlated phenotypes of self-reported headache and self-reported migraine can be meta-analysed together in theory and in practice to boost study power to identify more variants for headaches. This study has paved way for a large GWAS meta-analysis involving cohorts of different while genetically correlated headache phenotypes.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-022-00078-7.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 1","pages":"64-76"},"PeriodicalIF":0.0,"publicationDate":"2022-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9916267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Soluble Epoxide Hydrolase Activity Positively Correlates with Mortality in Heart Failure Patients with Preserved Ejection Fraction: Evidence from Metabolomics.","authors":"Liyuan Peng, Ziping Song, Chengcheng Zhao, Kudusi Abuduwufuer, Yanwen Wang, Zheng Wen, Li Ni, Chenze Li, Ying Yu, Yi Zhu, Hualiang Jiang, Jinshan Shen, Xiangrui Jiang, Chen Chen, Xu Zhang, Dao Wen Wang","doi":"10.1007/s43657-022-00069-8","DOIUrl":"10.1007/s43657-022-00069-8","url":null,"abstract":"<p><p>Epoxyeicosatrienoic acids (EETs) have pleiotropic endogenous cardiovascular protective effects and can be hydrolyzed to the corresponding dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Heart failure with preserved ejection fraction (HFpEF) has shown an increased prevalence and worse prognosis over the decades. However, the role of sEH activity in HFpEF remains unclear. We enrolled 500 patients with HFpEF and 500 healthy controls between February 2010 and March 2016. Eight types of sEH-related eicosanoids were measured according to target metabolomics, and their correlation with clinical endpoints was also analyzed. The primary endpoint was cardiac mortality, and the secondary endpoint was a composite of cardiac events, including heart failure (HF) readmission, cardiogenic hospitalization, and all-cause mortality. Furthermore, the effect of sEH inhibitors on cardiac diastolic function in HFpEF was investigated in vivo and in vitro. Patients with HFpEF showed significantly enhanced EET degradation by the sEH enzyme compared with healthy controls. More importantly, sEH activity was positively correlated with cardiac mortality in patients with HFpEF, especially in older patients with arrhythmia. A consistent result was obtained in the multiple adjusted models. Decreased sEH activity by the sEH inhibitor showed a significant effective effect on the improvement of cardiac diastolic function by ameliorating lipid disorders in cardiomyocytes of HFpEF mouse model. This study demonstrated that increased sEH activity was associated with cardiac mortality in patients with HFpEF and suggested that sEH inhibition could be a promising therapeutic strategy to improve diastolic cardiac function. Clinical trial identifier: NCT03461107 (https://clinicaltrials.gov).</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43657-022-00069-8.</p>","PeriodicalId":74435,"journal":{"name":"Phenomics (Cham, Switzerland)","volume":"3 1","pages":"34-49"},"PeriodicalIF":0.0,"publicationDate":"2022-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9147974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}