Publications by authors named "Luyun Wang"

18 Publications

  • Page 1 of 1

Strategies for multivariate analyses of imaging genetics study in Alzheimer's disease.

Neurosci Lett 2021 09 29;762:136147. Epub 2021 Jul 29.

School of Computer Science and Technology, Hangzhou Dianzi University, Hangzhou, Zhejiang 310018, China; Key Laboratory of Intelligent Image Analysis for Sensory and Cognitive Health, Ministry of Industry and Information Technology of China, Hangzhou, Zhejiang 310018, China.

Alzheimer's disease (AD) is an incurable neurodegenerative disease primarily affecting the elderly population. Early diagnosis of AD is critical for the management of this disease. Imaging genetics examines the influence of genetic variants (i.e., single nucleotide polymorphisms (SNPs)) on brain structure and function and many novel approaches of imaging genetics are proposed for studying AD. We review and synthesize the Alzheimer's Disease Neuroimaging Initiative (ADNI) genetic associations with quantitative disease endophenotypes including structural and functional neuroimaging, diffusion tensor imaging (DTI), positron emission tomography (PET), and fluid biomarker assays. In this review, we survey recent publications using neuroimaging and genetic data of AD, with a focus on methods capturing multivariate effects accommodating the large number variables from both imaging data and genetic data. We review methods focused on bridging the imaging and genetic data by establishing genotype-phenotype association, including sparse canonical correlation analysis, parallel independent component analysis, sparse reduced rank regression, sparse partial least squares, genome-wide association study, and so on. The broad availability and wide scope of ADNI genetic and phenotypic data has advanced our understanding of the genetic basis of AD and has nominated novel targets for future pharmaceutical therapy and biomarker development.
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http://dx.doi.org/10.1016/j.neulet.2021.136147DOI Listing
September 2021

Identifying and characterizing different stages toward Alzheimer's disease using ordered core features and machine learning.

Heliyon 2021 Jun 11;7(6):e07287. Epub 2021 Jun 11.

College of Computer Science and Technology, Hangzhou Dianzi University, Hangzhou, Zhejiang, 310018, China.

Based on the joint HCPMMP parcellation method we developed before, which divides the cortical brain into 360 regions, the concept of ordered core features (OCF) is first proposed to reveal the functional brain connectivity relationship among different cohorts of Alzheimer's disease (AD), late mild cognitive impairment (LMCI), early mild cognitive impairment (EMCI) and healthy controls (HC). A set of core network features that change significantly under the specifically progressive relationship were extracted and used as supervised machine learning classifiers. The network nodes in this set mainly locate in the frontal lobe and insular, forming a narrow band, which are responsible for cognitive impairment as suggested by previous finding. By using these features, the accuracy ranged from 86.0% to 95.5% in binary classification between any pair of cohorts, higher than 70.1%-91.0% when using all network features. In multi-group classification, the average accuracy was 75% or 78% for HC, EMCI, LMCI or EMCI, LMCI, AD against baseline of 33%, and 53.3% for HC, EMCI, LMCI and AD against baseline of 25%. In addition, the recognition rate was lower when combining EMCI and LMCI patients into one group of mild cognitive impairment (MCI) for classification, suggesting that there exists a big difference between early and late MCI patients. This finding supports the EMCI/LMCI inclusion criteria introduced by ADNI based on neuropsychological assessments.
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http://dx.doi.org/10.1016/j.heliyon.2021.e07287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220177PMC
June 2021

Soluble epoxide hydrolase deficiency attenuates lipotoxic cardiomyopathy via upregulation of AMPK-mTORC mediated autophagy.

J Mol Cell Cardiol 2021 05 27;154:80-91. Epub 2020 Dec 27.

Guangdong Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Cardiology, RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang Road, Guangzhou 510120, China; Department of Cardiology, The Eighth Affiliated Hospital of Sun Yat-sen University, 3025 Shennan Middle Road, Shen Zhen 518033, China. Electronic address:

Obesity-driven cardiac lipid accumulation can progress to lipotoxic cardiomyopathy. Soluble epoxide hydrolase (sEH) is the major enzyme that metabolizes epoxyeicosatrienoic acids (EETs), which have biological activity of regulating lipid metabolism. The current study explores the unknown role of sEH deficiency in lipotoxic cardiomyopathy and its underlying mechanism. Wild-type and Ephx2 knock out (sEH KO) C57BL/6 J mice were fed with high-fat diet (HFD) for 24 weeks to induce lipotoxic cardiomyopathy animal models. Palmitic acid (PA) was utilized to induce lipotoxicity to cardiomyocytes for in vitro study. We found sEH KO, independent of plasma lipid and blood pressures, significantly attenuated HFD-induced myocardial lipid accumulation and cardiac dysfunction in vivo. HFD-induced lipotoxic cardiomyopathy and dysfunction of adenosine 5'-monophosphate-activated protein kinase-mammalian target of rapamycin complex (AMPK-mTORC) signaling mediated lipid autophagy in heart were restored by sEH KO. In primary neonatal mouse cardiomyocytes, both sEH KO and sEH substrate EETs plus sEH inhibitor AUDA treatments attenuated PA-induced lipid accumulation. These effects were blocked by inhibition of AMPK or autophagy. The outcomes were supported by the results that sEH KO and EETs plus AUDA rescued HFD- and PA-induced impairment of autophagy upstream signaling of AMPK-mTORC, respectively. These findings revealed that sEH deficiency played an important role in attenuating myocardial lipid accumulation and provided new insights into treating lipotoxic cardiomyopathy. Regulation of autophagy via AMPK-mTORC signaling pathway is one of the underlying mechanisms.
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http://dx.doi.org/10.1016/j.yjmcc.2020.12.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068623PMC
May 2021

Erratum to: Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19.

Sci China Life Sci 2020 Oct 18;63(10):1617-1618. Epub 2020 Jun 18.

Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

1. In the abstract, we missed a piece of information. The correct sentence should be "In this retrospective study, we included 550 critically ill COVID-19 patients who need mechanical ventilation (63.5%) and oxygen therapy (35.6%) in Tongji Hospital, Wuhan, from February 1, 2020 to April 4, 2020." 2. We mistakenly put an approval number from Tongji Hospital ethics committee in the paper (IRBID: TJ-C20200113). The correct number should be TJ-IRB20200229. 3. We mistakenly filled some data in Table 1 and the correct Table 1 (the corrected data are in boldface) should be as follows.
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http://dx.doi.org/10.1007/s11427-020-1751-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306565PMC
October 2020

Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19.

Sci China Life Sci 2020 10 15;63(10):1515-1521. Epub 2020 May 15.

Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high fatality. The most urgent need is to find effective treatments. We sought to determine whether hydroxychloroquine (HCQ) application may reduce the death risk of critically ill COVID-19 patients. In this retrospective study, we included 550 critically ill COVID-19 patients who need mechanical ventilation in Tongji Hospital, Wuhan, from February 1, 2020 to April 4, 2020. All 550 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them were treated with oral HCQ treatment (200 mg twice a day for 7-10 days) in addition to the basic treatments. Primary endpoint is fatality of patients, and inflammatory cytokine levels were compared between HCQ and non-hydroxychloroquine (NHCQ) treatments. We found that fatalities are 18.8% (9/48) in HCQ group, which is significantly lower than 47.4% (238/502) in the NHCQ group (P<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4-14) days for the HCQ and NHCQ groups, respectively (P<0.05). The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 (8.3-118.9) pg mL at the beginning of the treatment to 5.2 (3.0-23.4) pg mL (P<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. These data demonstrate that addition of HCQ on top of the basic treatments is highly effective in reducing the fatality of critically ill patients of COVID-19 through attenuation of inflammatory cytokine storm. Therefore, HCQ should be prescribed as a part of treatment for critically ill COVID-19 patients, with possible outcome of saving lives. hydroxychloroquine, IL-6, mortalities, COVID-19.
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http://dx.doi.org/10.1007/s11427-020-1732-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228868PMC
October 2020

Organ function support in patients with coronavirus disease 2019: Tongji experience.

Front Med 2020 Apr 14;14(2):232-248. Epub 2020 May 14.

Department of Emergency and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Coronavirus disease 2019 (COVID-19) is a highly contagious disease and a serious threat to human health. COVID-19 can cause multiple organ dysfunction, such as respiratory and circulatory failure, liver and kidney injury, disseminated intravascular coagulation, and thromboembolism, and even death. The World Health Organization reports that the mortality rate of severe-type COVID-19 is over 50%. Currently, the number of severe cases worldwide has increased rapidly, but the experience in the treatment of infected patients is still limited. Given the lack of specific antiviral drugs, multi-organ function support treatment is important for patients with COVID-19. To improve the cure rate and reduce the mortality of patients with severe- and critical-type COVID-19, this paper summarizes the experience of organ function support in patients with severe- and critical-type COVID-19 in Optical Valley Branch of Tongji Hospital, Wuhan, China. This paper systematically summarizes the procedures of functional support therapies for multiple organs and systems, including respiratory, circulatory, renal, hepatic, and hematological systems, among patients with severe- and critical-type COVID-19. This paper provides a clinical reference and a new strategy for the optimal treatment of COVID-19 worldwide.
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http://dx.doi.org/10.1007/s11684-020-0774-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220847PMC
April 2020

Characteristics and variability of functional brain networks.

Neurosci Lett 2020 06 30;729:134954. Epub 2020 Apr 30.

College of Computer Science, Hangzhou Dianzi University, Hangzhou, Zhejiang, 310018, China; Key Laboratory of Intelligent Image Analysis for Sensory and Cognitive Health, Ministry of Industry and Information Technology of China, Hangzhou, Zhejiang, 310018, China.

Functional brain networks were constructed from functional magnetic resonance imaging (fMRI) data originating from 96 healthy adults. These networks possessed a total of 360 nodes, derived from the latest multi-modal brain parcellation method. A novel group network (overlay network) analysis model is proposed to study common attributes as well as differences found in the human brain by analysis of the functional brain network. Currently, the mean network is generally used to represent the group network. But mean networks have a modularity problem making them distinct from real networks. The overlay network is constructed by calculating the connections between the whole brain network regions, and then filtering the connections by limiting the threshold value. We find that the overlay network is closer to the real network condition of the group in terms of network characteristics related to modularity. Multiple network features are applied to investigate the discrepancies between the new group network and the mean network. Individual divergences between brain regions of everyone are also explored. Results show that the brain network of different people has a high consistency in the global measures, while there exist great differences for local measures in brain regions. Some brain regions show variability over other brain regions on most measures. In addition, we explored the impact of different thresholds on the overlay network and find that different thresholds have a greater impact on the clustering coefficient, maximized modularity, strength, and global efficiency.
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http://dx.doi.org/10.1016/j.neulet.2020.134954DOI Listing
June 2020

Alzheimer's disease, mild cognitive impairment, and normal aging distinguished by multi-modal parcellation and machine learning.

Sci Rep 2020 03 25;10(1):5475. Epub 2020 Mar 25.

College of Computer Science, Hangzhou Dianzi University, Hangzhou, Zhejiang, 310018, China.

A 360-area surface-based cortical parcellation is extended to study mild cognitive impairment (MCI) and Alzheimer's disease (AD) from healthy control (HC) using the joint human connectome project multi-modal parcellation (JHCPMMP) proposed by us. We propose a novel classification method named as JMMP-LRR to accurately identify different stages toward AD by integrating the JHCPMMP with the logistic regression-recursive feature elimination (LR-RFE). In three-group classification, the average accuracy is 89.0% for HC, MCI, and AD compared to previous studies using other cortical separation with the best classification accuracy of 81.5%. By counting the number of brain regions whose feature is in the feature subset selected with JMMP-LRR, we find that five brain areas often appear in the selected features. The five core brain areas are Fusiform Face Complex (L-FFC), Area 10d (L-10d), Orbital Frontal Complex (R-OFC), Perirhinal Ectorhinal (L-PeEc) and Area TG dorsal (L-TGd, R-TGd). The features corresponding to the five core brain areas are used to form a new feature subset for three classifications with the average accuracy of 80.0%. Results demonstrate the importance of the five core brain regions in identifying different stages toward AD. Experiment results show that the proposed method has better accuracy for the classification of HC, MCI, AD, and it also proves that the division of brain regions using JHCPMMP is more scientific and effective than other methods.
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http://dx.doi.org/10.1038/s41598-020-62378-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096533PMC
March 2020

Successful management of germanium poisoning-induced multiple organ dysfunctions by combined blood purification therapy.

Curr Med Res Opin 2020 04 5;36(4):687-691. Epub 2020 Feb 5.

Department of Organ Transplantation, Renmin Hospital, Wuhan University, Wuhan, China.

Blood purification therapy has not been applied in the detoxification of germanium compounds. This report described a case of germanium poisoning with renal failure, liver dysfunction, and acute pancreatitis which was successfully treated by continuous venovenous hemodiafiltration (CVVHDF) combined with plasmapheresis. A 58-year-old male was admitted to a local hospital due to polydipsia, polyuria, and weight loss for 2 months. The patient was definitely diagnosed with germanium poisoning and was treated with blood purification therapy, CVVHDF combined with plasmapheresis. The blood and urinary germanium concentrations decreased rapidly during the first week after the combined blood purification therapy. The blood germanium concentration gradually reduced to within the normal range within the next three weeks and fluctuated at a normal level. However, the urinary germanium concentration exceeded the normal level after three months, indicating an accumulation of germanium in the organs and tissues. The patient's clinical symptoms ameliorated and the functions of kidney, liver and pancreatitis gradually recovered. Combined CVVHDF with plasmapheresis is an effective treatment for germanium poisoning and the associated multiple organ dysfunctions.
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http://dx.doi.org/10.1080/03007995.2020.1717452DOI Listing
April 2020

Biosorption and Biodegradation of the Environmental Hormone Nonylphenol By Four Marine Microalgae.

Sci Rep 2019 03 27;9(1):5277. Epub 2019 Mar 27.

Department of Ecology, Institute of Hydrobiology, School of Life Science and Technology, Jinan University, Guangzhou, P.R. China.

Microalgae are the most abundant microorganisms in aquatic environments, and many possess the ability to remove organic contaminants. The presence of endocrine disruption compounds (EDCs) in many coastal marine systems and their associated risks have elicited great concern, especially in the case of nonylphenol (NP), which is classified as a priority contaminate by the U.S. EPA. In this context, batch experiments were conducted to investigate the intracellular absorption, extracellular adsorption and biodegradation of NP by four species of marine microalgae: Phaeocystis globosa, Nannochloropsis oculata, Dunaliella salina and Platymonas subcordiformis. The results showed a sharp reduction of NP in medium containing the four microalgal species during the first 24 h of incubation, and the four species exhibited the greatest capacity for NP adsorption and absorption within 24 h of culture. However, the amount of NP absorbed and adsorbed by all four microalgae decreased with increasing time in culture, and intracellular absorption was greater than extracellular adsorption. After 120 h of exposure to NP, the four species could biodegrade most of the NP in the medium, with efficiencies ranging from 43.43 to 90.94%. In sum, we found that the four microalgae have high biodegradation percentages and can thus improve the bioremediation of NP-contaminated water.
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http://dx.doi.org/10.1038/s41598-019-41808-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437302PMC
March 2019

The Dynamic EEG Microstates in Mental Rotation.

Sensors (Basel) 2018 Sep 3;18(9). Epub 2018 Sep 3.

School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200000, China.

Mental rotation is generally analyzed based on event-related potential (ERP) in a time domain with several characteristic electrodes, but neglects the whole spatial-temporal brain pattern in the cognitive process which may reflect the underlying cognitive mechanism. In this paper, we mainly proposed an approach based on microstates to examine the encoding of mental rotation from the spatial-temporal changes of EEG signals. In particular, we collected EEG data from 11 healthy subjects in a mental rotation cognitive task using 12 different stimulus pictures representing left and right hands at various rotational angles. We applied the microstate method to investigate the microstates conveyed by the event-related potential extracted from EEG data during mental rotation, and obtained four microstate modes (referred to as modes A, B, C, D, respectively). Subsequently, we defined several measures, including microstate sequences, topographical map, hemispheric lateralization, and duration of microstate, to characterize the dynamics of microstates during mental rotation. We observed that (1) the microstates sequence had a specified progressing mode, i.e., A → B → A ; (2) the activation of the right parietal occipital region was stronger than that of the left parietal occipital region according to the hemispheric lateralization of the microstates mode A; and (3) the duration of the second microstates mode A showed the shorter duration in the vertical stimuli, named "angle effect".
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http://dx.doi.org/10.3390/s18092920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165343PMC
September 2018

A Novel Nonlinear Dynamic Method for Stroke Rehabilitation Effect Evaluation Using EEG.

IEEE Trans Neural Syst Rehabil Eng 2017 12 25;25(12):2488-2497. Epub 2017 Aug 25.

Evaluating the effect of stroke rehabilitation based on electroencephalogram (EEG) is still a challenging problem. This paper presents a novel nonlinear dynamic complexity method for the evaluation of stroke rehabilitation effect from EEG signal. Our method calculates the nonlinearly separable degree (NLSD) of EEG signal, and then employs an indicator, called mean nonlinearly separable complexity degree (Mean_NLSD), to efficiently and accurately evaluate therapy effect of stroke patients. This paper under twelve stimuli conditions on eleven patients and eleven control subjects indicates that in general Mean_NLSD is smaller at the lesion regions and that the Mean_NLSD of the control subjects is stochastic. Compared with conventional spectral methods, such as mean power spectral density (PSD), Mean_NLSD is more sensitive and robust. Overall Mean_NLSD may offer a promising approach to facilitate the evaluation of stroke rehabilitation effect.
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http://dx.doi.org/10.1109/TNSRE.2017.2744664DOI Listing
December 2017

Relationship Between β-Blocker Therapy at Discharge and Clinical Outcomes in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

J Am Heart Assoc 2016 11 16;5(11). Epub 2016 Nov 16.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Background: The evidence supporting the use of β-blockers in patients with acute coronary syndrome after successful percutaneous coronary intervention has been inconsistent and scarce.

Methods And Results: Between March 1, 2009, and December 30, 2014, a total of 3180 eligible patients with acute coronary syndrome undergoing percutaneous coronary intervention were consecutively enrolled. The primary end point was all-cause death and the secondary end point was a composite of all-cause death, nonfatal myocardial infarction, heart failure readmission, and cardiogenic hospitalization. Patients were compared according to the use of β-blockers at discharge. Compared with the no β-blocker group, the risk of all-cause death was significantly lower in the β-blocker group (hazard ratio [HR], 0.33; 95% CI, 0.17-0.65 [P=0.001]). A consistent result was obtained in multiple adjusted model and propensity score-matched analysis. The use of β-blockers was also associated with decreased risk of composite of adverse cardiovascular events (HR, 0.47; 95% CI, 0.28-0.81 [P=0.006]), although statistical significance disappeared after multivariable adjustment and propensity score matching. Furthermore, we performed post hoc analysis for the subsets of patients and the results revealed that patients with non-ST-segment elevation myocardial infarction benefited the most from β-blocker therapy at discharge (HR, 0.04; 95% CI, 0.00-0.27 [P=0.001]), and the use of <50% of target dose was significantly associated with better outcome compared with no β-blocker use, rather than ≥50% of target dose.

Conclusions: The administration of relatively low β-blocker dose is associated with improved clinical outcomes among patients with acute coronary syndrome after successful percutaneous coronary intervention, especially for patients with non-ST-segment elevation myocardial infarction.
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http://dx.doi.org/10.1161/JAHA.116.004190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210364PMC
November 2016

Epoxyeicosatrienoic acids attenuating hypotonic-induced apoptosis of IMCD cells via γ-ENaC inhibition.

PLoS One 2014 8;9(4):e94400. Epub 2014 Apr 8.

Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China; Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.

Inner medulla collecting duct (IMCD) cells are the key part for urinary concentration. Hypotonic stress may trigger apoptosis of IMCD cells and induce renal injury. Epoxyeicosatrienoic acids (EETs) play an important role in anti-apoptosis, but their roles in hypotonic-induced apoptosis of IMCD cells are still unclear. Here we found increasing exogenous 11, 12-EET or endogenous EETs with Ad-CMV-CYP2C23-EGFP transfection decreased apoptosis of IMCD cells induced by hypotonic stress. Moreover, up-regulation of γ-ENaC induced by hypotonic stress was abolished by elevation of exogenous or endogenous EETs. Collectively, this study illustrated that EETs attenuated hypotonic-induced apoptosis of IMCD cells, and that regulation of γ-ENAC may be a possible mechanism contributing to the anti-apoptotic effect of EETs in response to hypotonic stress.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0094400PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979856PMC
December 2014

CYP2J3 gene delivery reduces insulin resistance via upregulation of eNOS in fructose-treated rats.

Cardiovasc Diabetol 2011 Dec 21;10:114. Epub 2011 Dec 21.

Department of Internal Medicine and The Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.

Accumulating evidence suggests that cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs) which play important roles in various pathophysiological processes. Interestingly, CYP-derived eicosanoids are vasodilatory, at least in part through their ability to activate eNOS and subsequent NO release. This study investigated the roles of eNOS in CYP2J3 gene delivery reducing blood pressure and improving insulin resistance in fructose-treated rats. CYP2J3 overexpression in vivo increased EET generation, reduced blood pressure and reversed insulin resistance as determined by insulin resistance index (HOMA-IR). Furthermore, administration of eNOS inhibitor L-NMMA significantly and partially abolished the beneficial effects of CYP2J3 gene delivery on hypertension and insulin resistance induced by fructose intake, and possible mechanism is associated with increased ET-1, ETA-receptor mRNA expression and reduced sensitivity of insulin to peripheral tissues and organs characterized by reduced activity of IRS-1/PI3K/AKT and AMPK signalling pathways. These data provide direct evidence that CYP2J3-derived EETs may alleviate insulin resistance at least in part through upregulated eNOS expression.
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http://dx.doi.org/10.1186/1475-2840-10-114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313895PMC
December 2011

Gene delivery of cytochrome p450 epoxygenase ameliorates monocrotaline-induced pulmonary artery hypertension in rats.

Am J Respir Cell Mol Biol 2010 Dec 29;43(6):740-9. Epub 2010 Jan 29.

Department of Internal Medicine and Gene Therapy Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Pulmonary arterial hypertension (PAH) is a life-threatening disease that leads to progressive pulmonary hypertension, right heart failure, and death. Endothelial dysfunction and inflammation were implicated in the pathogenesis of PAH. Epoxyeicosatrienoic acids (EETs), products of the cytochrome P450 epoxygenase metabolism of arachidonic acid, are potent vasodilators that possess anti-inflammatory and other protective properties in endothelial cells. We investigated whether gene delivery with the human cytochrome P450 epoxygenase 2J2 (CYP2J2) ameliorates monocrotaline (MCT)-induced pulmonary hypertension in rats. Significant pulmonary hypertension developed 3 weeks after the administration of MCT, but gene therapy with CYP2J2 significantly attenuated the development of pulmonary hypertension and pulmonary vascular remodeling, without causing changes in systemic arterial pressure or heart rate. These effects were associated with increased pulmonary endothelial NO synthase (eNOS) expression and its activity, inhibition of inflammation in the lungs, and transforming growth factor (TGF)-β/type II bone morphogenetic protein receptor (BMPRII)-drosophila mothers against decapentaplegic proteins (Smads) signaling. Collectively, these data suggest that gene therapy with CYP2J2 may have potential as a novel therapeutic approach to this progressive and oftentimes lethal disorder.
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http://dx.doi.org/10.1165/rcmb.2009-0161OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993093PMC
December 2010

Increased CYP2J3 expression reduces insulin resistance in fructose-treated rats and db/db mice.

Diabetes 2010 Apr 12;59(4):997-1005. Epub 2010 Jan 12.

Department of Internal Medicine and The Institute of Hypertension, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Objective: Accumulating evidence suggests that cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play crucial and diverse roles in cardiovascular homeostasis. The anti-inflammatory, antihypertensive, and pro-proliferative effects of EETs suggest a possible beneficial role for EETs on insulin resistance and diabetes.

Research Design And Methods: This study investigated the effects of CYP2J3 epoxygenase gene therapy on insulin resistance and blood pressure in diabetic db/db mice and in a model of fructose-induced hypertension and insulin resistance in rats.

Results: CYP2J3 gene delivery in vivo increased EET generation, reduced blood pressure, and reversed insulin resistance as determined by plasma glucose levels, homeostasis model assessment insulin resistance index, and glucose tolerance test. Furthermore, CYP2J3 treatment prevented fructose-induced decreases in insulin receptor signaling and phosphorylation of AMP-activated protein kinases (AMPKs) in liver, muscle, heart, kidney, and aorta. Thus, overexpression of CYP2J3 protected against diabetes and insulin resistance in peripheral tissues through activation of insulin receptor and AMPK pathways.

Conclusions: These results highlight the beneficial roles of the CYP epoxygenase-EET system in diabetes and insulin resistance.
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http://dx.doi.org/10.2337/db09-1241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844847PMC
April 2010

Generation, compression, and propagation of pulse trains in the nonlinear Schrödinger equation with distributed coefficients.

Phys Rev E Stat Nonlin Soft Matter Phys 2005 Sep 15;72(3 Pt 2):036614. Epub 2005 Sep 15.

College of Physics and Electronics Engineering, and Institute of Theoretical Physics, Shanxi University, Taiyuan 030006, China.

The generalized nonlinear Schrödinger model with distributed dispersion, nonlinearity, and gain or loss is considered and the explicit, analytical solutions describing the dynamics of bright solitons on a continuous-wave background are obtained in quadratures. Then, the generation, compression, and propagation of pulse trains are discussed in detail. The numerical results show that solitons can be compressed by choosing the appropriate control fiber system, and pulse trains generated by modulation instability can propagate undistorsted along fibers with distributed parameters by controlling appropriately the energy of each pulse in the pulse train.
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http://dx.doi.org/10.1103/PhysRevE.72.036614DOI Listing
September 2005
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