22 results on '"Cui, Liang"'
Search Results
2. Dual-specificity phosphatase 12 attenuates oxidative stress injury and apoptosis in diabetic cardiomyopathy via the ASK1-JNK/p38 signaling pathway
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Huan, Li, Qin, Yang, Zhen, Huang, Cui, Liang, Dian-Hong, Zhang, Hui-Ting, Shi, Jia-Qi, Du, Bin-Bin, Du, and Yan-Zhou, Zhang
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Mice ,Oxidative Stress ,Diabetes Mellitus, Type 2 ,Diabetic Cardiomyopathies ,Physiology (medical) ,JNK Mitogen-Activated Protein Kinases ,Animals ,Dual-Specificity Phosphatases ,Apoptosis ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,Signal Transduction - Abstract
Diabetic cardiomyopathy (DCM) is ventricular dysfunction that occurs in patients with diabetes mellitus (DM), independent of recognized risk factors, such as coronary artery disease, hypertension, and valvular heart disease. Dual-specificity phosphatase 12 (DUSP12) is a dual-specificity phosphatase expressed in all tissues. Genome-wide linkage studies have found an association between DUSP12 and type 2 diabetes (T2D). However, the role of DUSP12 in DCM remains largely unknown. Ubiquitously expressed DUSP12 is involved in nonalcoholic fatty liver disease, bacterial infection, and myocardial hypertrophy and plays a critical role in tumorigenesis. Herein, we observed an increased expression of DUSP12 in a hyperglycemia cell model and a high-fat diet (HFD) mouse model. Heart-specific DUSP12-deficient mice showed severe cardiac dysfunction and remodeling induced by an HFD. DUSP12 deficiency exacerbated oxidative stress injury and apoptosis, whereas DUSP12 overexpression had the opposite effect. At the molecular level, DUSP12 physically bound to apoptotic signal-regulated kinase 1 (ASK1), promoted its dephosphorylation, and inhibited its action on c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. Rescue experiments have shown that oxidative stress injury and apoptosis, exacerbated by DUSP12 deficiency, are alleviated by ASK1 inhibition. Therefore, we consider DUSP12 an important signaling pathway in DCM.
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- 2022
3. Synthesis of Azetidine Nitrones and Exomethylene Oxazolines through a Copper(I)-Catalyzed 2,3-Rearrangement and 4π-Electrocyclization Cascade Strategy
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Jin-Qi Zhang, Pei-Wen Qiu, Cui Liang, and Dong-Liang Mo
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Oximes ,Organic Chemistry ,Azetidines ,Nitrogen Oxides ,Physical and Theoretical Chemistry ,Biochemistry ,Copper ,Catalysis - Abstract
A variety of azetidine nitrones are prepared in moderate to good yields through copper(I) combined with 2-aminopyridine to catalyze skeletal rearrangement of
- Published
- 2022
4. Endothelial cell‐released extracellular vesicles trigger pyroptosis and vascular inflammation to induce atherosclerosis through the delivery of HIF1A‐AS2
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Pengcheng Li, Jin Hong, Cui Liang, Yapeng Li, Lu Gao, Leiming Wu, Rui Yao, and Yanzhou Zhang
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Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2023
5. Chan–Lam Reaction and Lewis Acid Promoted 1,3-Rearrangement of N–O Bonds to Prepare N-(2-Hydroxyaryl)pyridin-2-ones
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Hong-Yan Bi, Qing-Yan Wu, Xiao-Mei Zhou, Hui-Juan Xu, Cui Liang, Dong-Liang Mo, and Xiao-Pan Ma
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Organic Chemistry ,Physical and Theoretical Chemistry ,Biochemistry - Published
- 2022
6. Cinchonidine-Catalyzed Synthesis of Oxazabicyclo[4.2.1]nonanones from N-Aryl-α,β-unsaturated Nitrones and 1-Ethynylnaphthalen-2-ols
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Cui Wei, Zhou Zhou, Guang-Li Pang, Cui Liang, and Dong-Liang Mo
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Organic Chemistry ,Physical and Theoretical Chemistry ,Biochemistry - Published
- 2022
7. Nickel(II)-Catalyzed [3 + 2] Cycloaddition of Nitrones and Allenoates to Access N-Vinylindoles and N-Vinylpyrroles
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Wei-Min Shi, Dong-Liang Mo, Pei-Pei Xu, Cui Liang, Jun-Yi Liao, Jia-Jie Zhang, and Gui-Fa Su
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Reaction conditions ,Chemistry ,Organic Chemistry ,Substrate (chemistry) ,chemistry.chemical_element ,Mass spectrometry ,Biochemistry ,Medicinal chemistry ,Cycloaddition ,Enamine ,Catalysis ,chemistry.chemical_compound ,Nickel ,Functional group ,Physical and Theoretical Chemistry - Abstract
A variety of N-vinylindoles and N-vinylpyrroles were prepared in moderate to good yields through the nickel(II)-catalyzed [3 + 2] cycloaddition of α,β-unsaturated nitrones with allenoates under mild reaction conditions. A rational mechanism for the formation of N-vinylindoles was proposed based on the 18O-labeled experiments and key intermediates detected by high-resolution mass spectrometry trace experiments. The present method highlights a nickel(II)-controlled cyclization, atom-economical reaction, broad substrate scope, good functional group tolerance, and high Z-stereoselectivity for the enamine bond.
- Published
- 2021
8. Copper(<scp>i</scp>)-catalyzed [4 + 2] cycloaddition of aza-ortho-quinone methides with bicyclic alkenes
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Gui-Fa Su, Cheng-Xue Pan, Cui Liang, Lei Lu, Yu-Feng Liang, Dong-Liang Mo, and Jiang-Ke Qin
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Single electron ,Bicyclic molecule ,Chemistry ,Organic Chemistry ,chemistry.chemical_element ,Physical and Theoretical Chemistry ,Biochemistry ,Medicinal chemistry ,Copper ,Cycloaddition ,Stereocenter ,Quinone ,Catalysis - Abstract
A variety of tetrahydroquinoline-fused bicycles bearing multiple stereocenters are prepared in good yields with high diastereoselectivity through Cu2O-catalyzed [4 + 2] cycloaddition of aza-ortho-quinone methides (ao-QMs) with bicyclic alkenes. Mechanistic studies reveal that the Cu(i) catalyst not only promotes the formation of ao-QMs through a radical process by single electron transfer but also accelerates [4 + 2] cycloaddition. The reaction was easily performed on gram scale and the obtained tetrahydroquinoline-fused bicycles can be converted to diverse tetrahydroquinoline scaffolds.
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- 2021
9. Nickel(II)-Catalyzed Oxygen Transfer Reaction of N-Vinyl Nitrones to Prepare 2-(Pyridin-2-yl)ethanols
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Cui Liang, Gui-Fa Su, Gong-Gui Yan, Jing-Xuan Lan, Zou Ning, and Dong-Liang Mo
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Oxygen transfer ,010405 organic chemistry ,Carbazole ,Organic Chemistry ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Medicinal chemistry ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,Nickel ,chemistry ,Atom economy ,Yield (chemistry) ,Physical and Theoretical Chemistry - Abstract
A nickel(II)-catalyzed oxygen transfer reaction of dibenzylideneacetone-derived N-vinyl-α,β-unsaturated nitrones has been identified for the preparation of polysubstituted 2-(pyridin-2-yl)ethanols in good yields with high atom economy. The scope of the method is described, and mechanistic experiments are discussed. The reaction was easily performed at gram scales, and pyrido[2,3-c]carbazole was obtained in moderate yield over three steps.
- Published
- 2020
10. Palladacycle-Catalyzed Regioselective Heck Reaction Using Diaryliodonium Triflates and Aryl Iodides
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Lu Lei, Pei-Sen Zou, Zhi-Xin Wang, Cui Liang, Cheng Hou, and Dong-Liang Mo
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Organic Chemistry ,Physical and Theoretical Chemistry ,Biochemistry - Abstract
We describe a P-containing palladacycle-catalyzed regioselective Heck reaction of 2,3-dihydrofuran with diaryliodonium salts and aryl iodides to afford 2-aryl-2,5-dihydrofurans and 2-aryl-2,3-dihydrofurans, respectively, in good yields. Mechanistic studies revealed that the oxidative addition of diaryliodonium salts to palladacycles to form Pd(IV) species showed high chemoselectivity and that electron-rich aryl moieties were preferentially transferred to the Heck product. DFT calculations indicated that the regioselectivity-determining step is the reductive elimination reaction rather than the isomerization and reinsertion of Pd(IV)-hydride intermediates into the double bond.
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- 2022
11. Iron(III)/Copper(II)-Cocatalyzed Cycloaddition/[3,3]-Rearrangement/N–O Bond Cleavage To Prepare Polysubstituted Pyrrolizines from N-Vinyl-α,β-Unsaturated Nitrones and Activated Alkynes
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Cui Liang, Cheng-Xue Pan, Zou Ning, Ji-Wen Jiao, Dong-Liang Mo, Gui-Fa Su, and Feng Yu
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010405 organic chemistry ,Ligand ,Organic Chemistry ,chemistry.chemical_element ,010402 general chemistry ,Ring (chemistry) ,01 natural sciences ,Biochemistry ,Copper ,Medicinal chemistry ,Cycloaddition ,0104 chemical sciences ,Kinetic resolution ,chemistry ,Physical and Theoretical Chemistry ,Bond cleavage - Abstract
An efficient one-pot synthesis of polysubstituted pyrrolizines from N-vinyl- α,β-unsaturated nitrones and activated alkynes through iron(III)/copper(II)-cocatalyzed [3 + 2] cycloaddition/[3,3]-rearrangement and sequential N-O bond cleavage was developed. The reaction first underwent [3 + 2] cycloaddition and [3,3]-rearrangement to afford nine-membered N-heterocycles, and then a controlled N-O bond cleavage of nine-membered rings by iron(III)/copper(II) cocatalysts delivered pyrrolizine scaffolds. A kinetic resolution of nine-membered ring compounds was achieved for the first time by using copper(II) acetate combined with a chiral PyBox ligand.
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- 2019
12. A Novel Approach to Double the Sensitivity of Polarization Maintaining Interferometric Fiber Optic Gyroscope
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Dengwei Zhang, Cui Liang, and Nan Li
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Letter ,02 engineering and technology ,lcsh:Chemical technology ,Fiber coil ,01 natural sciences ,Biochemistry ,polarization maintaining interferometric fiber optic gyroscope ,Analytical Chemistry ,010309 optics ,020210 optoelectronics & photonics ,Optics ,0103 physical sciences ,0202 electrical engineering, electronic engineering, information engineering ,Miniaturization ,lcsh:TP1-1185 ,Electrical and Electronic Engineering ,Instrumentation ,Physics ,fiber polarization combiner/splitter ,business.industry ,Fibre optic gyroscope ,Polarization (waves) ,Ray ,Atomic and Molecular Physics, and Optics ,Interferometry ,Orthogonal coordinates ,double sensitivity ,business - Abstract
In this paper, a novel optical approach to double the sensitivity to angular rate of interferometric fiber optic gyroscope (IFOG) is proposed. Two fiber polarization combiner/splitters (FPCSs), as the key components, are added in the traditional IFOG light path. The FPCSs are able to either combine two orthogonal polarizations transmitting at two different polarization-maintaining fibers (PMFs) into the two orthogonal axes of one PMF, respectively, or split two polarizations transmitting at the two orthogonal axes of one PMF into two polarizations to transmit at two different PMFs, respectively. Through the specific placement and coupling of these two FPCSs, the incident light can transmit twice along the polarization-maintaining fiber coil (PMFC). The novel approach is verified experimentally and the experimental results show consistency with the theoretical analysis. The proposed approach is able to double the sensitivity of IFOGs and can increase the signal-to-noise ratio (SNR) without increasing the length of PMFC, which is very susceptible to environmental influences and is of great significance in the technical improvement of IFOGs, as well as the miniaturization of IFOGs.
- Published
- 2020
13. Formal [7 + 2] Cycloaddition of Arynes with N-Vinyl-α,β-Unsaturated Nitrones: Synthesis of Benzoxazonines and Their N-O Bond Cleavage
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Liang-Gui Li, Zhao Hongping, Dong-Liang Mo, Xiao-Pan Ma, Cui Liang, and Min Du
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010405 organic chemistry ,Organic Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Medicinal chemistry ,Aryne ,Cycloaddition ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Stereoselectivity ,Phenols ,Physical and Theoretical Chemistry ,Benzopyrans ,Bond cleavage - Abstract
Various benzoxazonines were synthesized through a formal [7 + 2] cycloaddition of arynes with N-vinyl-α,β-unsaturated nitrones under mild conditions. Controllable N–O bond cleavage of benzoxazonines afforded polysubstituted pyrrole-tethered benzopyrans and acyclic ketone-substituted phenols in moderate to good yields. Further transformations provided a facile approach to access useful building blocks with specific stereoselectivity.
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- 2018
14. Melatonin improves cardiac function in a mouse model of heart failure with preserved ejection fraction
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Cui Liang, Sen Guo, Dan Wang, Xiaoyan Zhao, Jianzeng Dong, Sheng Tu, Lu Gao, Li-Na Li, Haibo Yang, Ling Li, Yuzhou Liu, and Yuan Liu
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0301 basic medicine ,Male ,Necrosis ,Clinical Biochemistry ,Adipose tissue ,Apoptosis ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Biochemistry ,Antioxidants ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Adipocyte ,lcsh:QH301-705.5 ,Melatonin ,lcsh:R5-920 ,medicine.symptom ,lcsh:Medicine (General) ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,Research Paper ,Cardiac function curve ,medicine.medical_specialty ,NF-E2-Related Factor 2 ,Diet, High-Fat ,03 medical and health sciences ,Adipokines ,Internal medicine ,medicine ,Animals ,Obesity ,Heart Failure ,business.industry ,Myocardium ,Organic Chemistry ,Stroke Volume ,HFpEF ,Mice, Inbred C57BL ,Disease Models, Animal ,Oxidative Stress ,030104 developmental biology ,Endocrinology ,chemistry ,lcsh:Biology (General) ,business ,Heart failure with preserved ejection fraction ,Oxidative stress ,CTRP3 - Abstract
Melatonin has been shown to inhibit myocardial infarction-induced apoptosis, its function in heart failure with preserved ejection fraction (HFpEF) has not been investigated. This study aimed to investigate whether melatonin attenuates obesity-related HFpEF. Male mice were fed a high-fat diet (HFD) from weaning to 6 months of age to induce HFpEF. The mice were orally administered melatonin (50 mg/kg) by 3 weeks. Diastolic function was significantly improved by melatonin supplementation in mice fed an HFD. Melatonin attenuated obesity-induced myocardial oxidative stress and apoptosis and promoted the secretion of C1q/tumour necrosis factor-related protein 3 (CTRP3) by adipose tissue. And depletion of circulating CTRP3 largely abolished melatonin-mediated cardio-protection. Melatonin-mediated secretion of adipocyte-derived CTRP3 activated NF-E2-related factor 2 (Nrf2), which were largely abrogated by knocking down CTRP3 in adipocytes or Nrf2 in cardiomyocytes. Nrf2 activation was mediated by miR-200a, and a miR-200a antagomir offset the effects of melatonin-conditioned medium on Nrf2 expression. Our results indicate that melatonin can be used to treat and prevent obesity-related HFpEF., Graphical abstract fx1, Highlights • Melatonin attenuates obesity-related heart failure with preserved ejection fraction. • Melatonin attenuates obesity-induced myocardial injury via adipose tissue-derived CTRP3. • Melatonin-mediated secretion of adipocyte-derived CTRP3 activates Nrf2 by miR-200a.
- Published
- 2018
15. C1QTNF1 attenuates angiotensin II-induced cardiac hypertrophy via activation of the AMPKa pathway
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Zhen Huang, Lu Gao, Cui Liang, Leiming Wu, Dianhong Zhang, Lili Xiao, Yapeng Li, Yanzhou Zhang, Pengcheng Li, Rui Yao, Zheng Wang, and Binbin Du
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0301 basic medicine ,Cardiac function curve ,Male ,medicine.medical_specialty ,Inflammation ,Cardiomegaly ,Biochemistry ,Rats, Sprague-Dawley ,03 medical and health sciences ,Mice ,AMP-Activated Protein Kinase Kinases ,Adipokines ,Fibrosis ,Physiology (medical) ,Internal medicine ,medicine ,Myocyte ,Animals ,Vasoconstrictor Agents ,Myocytes, Cardiac ,Phosphorylation ,PI3K/AKT/mTOR pathway ,Cells, Cultured ,Mice, Knockout ,Chemistry ,Angiotensin II ,medicine.disease ,Rats ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Heart failure ,cardiovascular system ,Tumor necrosis factor alpha ,medicine.symptom ,Protein Kinases ,Signal Transduction - Abstract
Rationale Complement C1q tumor necrosis factor related proteins (C1QTNFs) have been reported to have diverse biological influence on the cardiovascular system. C1QTNF1 is a member of the CTRP superfamily. C1QTNF1 is expressed in the myocardium; however, its function in myocytes has not yet been investigated. Objective To systematically investigate the roles of C1QTNF1 in angiotensin II (Ang II)-induced cardiac hypertrophy. Methods and results C1QTNF1 knock-out mice were used with the aim of determining the role of C1QTNF1 in cardiac hypertrophy in the adult heart. Data from experiments showed that C1QTNF1 was up-regulated during cardiac hypertrophic processes, which were triggered by increased reactive oxygen species. C1QTNF1 deficiency accelerated cardiac hypertrophy, fibrosis, inflammation responses, and oxidative stress with deteriorating cardiac dysfunction in the Ang II-induced cardiac hypertrophy mouse model. We identified C1QTNF1 as a negative regulator of cardiomyocyte hypertrophy in Ang II-stimulated neonatal rat cardiomyocytes using the recombinant human globular domain of C1QTNF1 and C1QTNF1 siRNA. Injection of the recombinant human globular domain of C1QTNF1 also suppressed the Ang II-induced cardiac hypertrophic response in vivo. The anti-hypertrophic effects of C1QTNF1 rely on AMPKa activation, which inhibits mTOR P70S6K phosphorylation. An AMPKa inhibitor abrogated the anti-hypertrophic effects of the recombinant human globular domain of C1QTNF1 both in vivo and vitro. Moreover, C1QTNF1-mediated AMPKa activation was triggered by the inhibition of PDE1-4, which subsequently activated the cAMP/PKA/LKB1 pathway. Conclusion Our results demonstrated that C1QTNF1 improves cardiac function and inhibits cardiac hypertrophy and fibrosis by increasing and activating AMPKa, suggesting that C1QTNF1 could be a therapeutic target for cardiac hypertrophy and heart failure.
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- 2018
16. Hyperoside Suppresses Lipopolysaccharide-induced Inflammation and Apoptosis in Human Umbilical Vein Endothelial Cells
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Ling Li, Haibo Yang, Yuan Liu, Yawei Xu, Yanqiang Zhou, Yin-tao Zhao, Cui Liang, and Xiaoyan Zhao
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0301 basic medicine ,Lipopolysaccharides ,Lipopolysaccharide ,Cell Survival ,Inflammation ,Apoptosis ,030204 cardiovascular system & hematology ,Pharmacology ,Biochemistry ,Models, Biological ,Umbilical vein ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Genetics ,medicine ,Human Umbilical Vein Endothelial Cells ,Humans ,RNA, Messenger ,NF-kappa B ,NFKB1 ,Toll-Like Receptor 4 ,IκBα ,030104 developmental biology ,chemistry ,TLR4 ,Cytokines ,Tumor necrosis factor alpha ,Quercetin ,medicine.symptom ,Inflammation Mediators - Abstract
Finding the novel drug from the effective components of traditional Chinese herbal medicine is a hotspot of the modern pharmacological research. Hyperoside (HYP) belongs to flavonoid glycosides, and it has various properties, such as anti-inflammation, anti-spasm, anti-diuretic, antitussive, lowering blood pressure, and lowering cholesterol effects as well as protective effects for the cardiac and cerebral blood vessels. The purpose of this study was to investigate the effects of HYP on inflammatory and apoptotic responses in vascular endothelial cells stimulated by lipopolysaccharide (LPS) and further to identify the possible mechanisms underlying these effects. In our study, human umbilical vein endothelial cells (HUVECs) were stimulated with 1 μg/mL LPS in the presence or absence of HYP (10, 20 and 50 μmol/L). Our results indicated that HYP alone exerted no cytotoxicity on HUVECs, while it had an up-regulatory effect on the viability of HUVECs induced by LPS in a dose-dependent manner; increased mRNA expression of IL-1β, IL-6, TNFα and iNOS induced by LPS was attenuated after treatment with HYP both in a dose-and time-dependent manner; LPS-induced HUVECs apoptosis and cleaved-caspase 8, 9, 3 were all significantly reduced by HYP. Furthermore, the possible pathway involved in apoptosis and inflammation by HYP was detected, and the results showed that when treated with HYP, LPS-induced mitochondrial membrane instability was significantly inhibited through up-regulation of Bcl-2 and down-regulation of Bax. Furthermore, the expression of TLR4 and the phosphorylation of IκBα and p65 in LPS-treated cells were blocked by HYP. Our results suggested that HYP treatment prevented HUVECs from LPSinduced inflammation and apoptosis responses, which might be mediated by inhibiting TLR4/NFκB pathway.
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- 2017
17. Effect of additives on the morphology and properties of poly(vinylidene fluoride) blend hollow fiber membrane prepared by the thermally induced phase separation method
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Yoshikage Ohmukai, Tatsuo Maruyama, Cui Liang, Saeid Rajabzadeh, and Hideto Matsuyama
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Materials science ,technology, industry, and agriculture ,Membrane structure ,Filtration and Separation ,macromolecular substances ,Biochemistry ,Contact angle ,chemistry.chemical_compound ,Membrane ,Spherulite ,Chemical engineering ,chemistry ,Hollow fiber membrane ,Ultimate tensile strength ,Polymer chemistry ,General Materials Science ,Fiber ,Physical and Theoretical Chemistry ,Methyl methacrylate - Abstract
The effects of poly(vinylpyrrolidone ) (PVP) and poly(methyl methacrylate) (PMMA) additives on poly(vinylidene fluoride) (PVDF) hollow fiber membranes fabricated via the thermally induced phase separation process were studied. The addition of PVP showed a significant effect on the membrane structure, while addition of PMMA had little effect. In the PVDF/PVP blend membrane, the growth of spherulites was effectively inhibited due to the low compatibility between PVDF and PVP. An asymmetric structure consisting of a dense skin layer near the outer surface and a spherulite structure inside the membrane was obtained in this blend membrane. Measurements of tensile strength and water contact angle were also carried out. In contrast to the addition of PMMA, the addition of PVP significantly improved the maximum stress, elongation and hydrophilicity of membranes. Filtration experiments with BSA solution showed that PVDF/PVP membranes had much better fouling resistance than PVDF/PMMA and plain PVDF membranes.
- Published
- 2012
18. Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection.
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Cui, Liang, Pang, Junxiong, Lee, Yie Hou, Ooi, Eng Eong, Ong, Choon Nam, Leo, Yee Sin, and Tannenbaum, Steven R.
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DENGUE , *DENGUE viruses , *METABOLOMICS , *DENGUE hemorrhagic fever , *METABOLITES , *ASPARTATE aminotransferase - Abstract
Dengue virus (DENV) is the most prevalent arbovirus leading to an estimated 100 million symptomatic dengue infections every year. DENV can cause a spectrum of clinical manifestations, ranging from mild dengue fever (DF) to more life threatening forms such as dengue hemorrhagic fever (DHF). The clinical symptoms of DHF become evident typically at the critical phase of infection (5–7 days after onset of fever), yet the mechanisms that trigger transition from DF to DHF are not well understood. We performed a mass spectrometry-based metabolomic profiling of sera from adult DF and DHF patients at the critical and recovery phases of infection. There were 29 differentially expressed metabolites identified between DF and DHF at the critical phase. These include bile acids, purines, acylcarnitines, phospholipids, and amino acids. Bile acids were observed up to 5 fold higher levels among DHF compared to DF patients and were significantly correlated to the higher levels of aspartate transaminase (AST) and alanine transaminase (ALT), suggestive of liver injury among DHF. Uric acid, the most abundant antioxidant in the blood, was observed to be 1.5 fold lower among DHF compared to DF patients. This could result in decreased capacity of endogenous antioxidant defense and elevated oxidative stress among DHF patients. In the recovery phase, the levels of eight metabolites were still significantly higher or lower among DHF patients, including chenodeoxyglycocholic acid, one of the bile acids observed at the critical phase. This indicates potential prolonged adverse impact on the liver due to DENV infection in DHF patients. Our study identified altered metabolic pathways linked to DHF in the critical and recovery phases of dengue infection and provided insights into the different host and DENV interactions between DF and DHF. The results advance our understanding on the mechanisms of DHF pathogenesis, alluding to possible novel therapeutic targets to dengue management. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
19. Molecular Analysis of Serum and Bronchoalveolar Lavage in a Mouse Model of Influenza Reveals Markers of Disease Severity That Can Be Clinically Useful in Humans
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Steven R. Tannenbaum, Jianzhu Chen, Gino V. Limmon, Cui Liang, Bevin P. Engelward, Li Liang, Yadunanda Kumar, Eng Eong Ooi, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Kumar, Yadunanda, Engelward, Bevin P., Chen, Jianzhu, and Tannenbaum, Steven Robert
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Proteomics ,Viral Diseases ,Pathology ,Proteome ,lcsh:Medicine ,medicine.disease_cause ,Biochemistry ,Severity of Illness Index ,Mice ,Influenza A Virus, H1N1 Subtype ,Influenza A virus ,lcsh:Science ,Immune Response ,media_common ,Multidisciplinary ,medicine.diagnostic_test ,Proteomic Databases ,Convalescence ,Acute-phase protein ,Blood proteins ,Host-Pathogen Interaction ,Infectious Diseases ,Medicine ,Cytokines ,Bronchoalveolar Lavage Fluid ,Research Article ,medicine.medical_specialty ,media_common.quotation_subject ,Immunology ,Acute Lung Injury ,Viremia ,Biology ,Lung injury ,Microbiology ,Orthomyxoviridae Infections ,Virology ,medicine ,Animals ,Humans ,Plasma Proteins ,lcsh:R ,Proteins ,medicine.disease ,Influenza ,Animal Models of Infection ,Viral Disease Diagnosis ,Disease Models, Animal ,Bronchoalveolar lavage ,Serum Amyloid P Component ,lcsh:Q ,Infectious Disease Modeling ,Biomarkers - Abstract
Background: Management of influenza, a major contributor to the worldwide disease burden, is complicated by lack of reliable methods for early identification of susceptible individuals. Identification of molecular markers that can augment existing diagnostic tools for prediction of severity can be expected to greatly improve disease management capabilities. Methodology/Principal Findings: We have analyzed cytokines, proteome flux and protein adducts in bronchoalveolar lavage (BAL) and sera from mice infected with influenza A virus (PR8 strain) using a previously established non-lethal model of influenza infection. Through detailed cytokine and protein adduct measurements of murine BAL, we first established the temporal profile of innate and adaptive responses as well as macrophage and neutrophil activities in response to influenza infection. A similar analysis was also performed with sera from a longitudinal cohort of influenza patients. We then used an iTRAQ-based, comparative serum proteome analysis to catalog the proteome flux in the murine BAL during the stages correlating with “peak viremia,” “inflammatory damage,” as well as the “recovery phase.” In addition to activation of acute phase responses, a distinct class of lung proteins including surfactant proteins was found to be depleted from the BAL coincident with their “appearance” in the serum, presumably due to leakage of the protein following loss of the integrity of the lung/epithelial barrier. Serum levels of at least two of these proteins were elevated in influenza patients during the febrile phase of infection compared to healthy controls or to the same patients at convalescence. Conclusions/Significance: The findings from this study provide a molecular description of disease progression in a mouse model of influenza and demonstrate its potential for translation into a novel class of markers for measurement of acute lung injury and improved case management., Singapore. National Research Foundation, Singapore-MIT Alliance for Research and Technology (ID-IRG research program)
- Published
- 2014
20. Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever.
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Cui, Liang, Lee, Yie Hou, Thein, Tun Linn, Fang, Jinling, Pang, Junxiong, Ooi, Eng Eong, Leo, Yee Sin, Ong, Choon Nam, and Tannenbaum, Steven R.
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DENGUE , *SEROTONIN , *METABOLOMICS , *BLOOD serum analysis , *HEMATOLOGY , *BIOCHEMISTRY - Abstract
Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (<96 h) was used to globally probe the serum metabolome to uncover early prognostic biomarkers of DHF. We identified 20 metabolites that are differentially enriched (p<0.05, fold change >1.5) in the serum, among which are two products of tryptophan metabolism–serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved the prognosis performance (AUC = 0.92, sensitivity = 77.8%, specificity = 95.8%), suggesting this duplex panel as accurate metrics for the early prognosis of DHF. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
21. Serum Metabolome and Lipidome Changes in Adult Patients with Primary Dengue Infection.
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Cui, Liang, Lee, Yie Hou, Kumar, Yadunanda, Xu, Fengguo, Lu, Kun, Ooi, Eng Eong, Tannenbaum, Steven R., and Ong, Choon Nam
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METABOLOMICS , *DENGUE , *LIQUID chromatography , *OXIDATION , *PHOSPHOLIPIDS , *METABOLISM , *DISEASE risk factors - Abstract
Background: Dengue virus (DENV) is the most widespread arbovirus with an estimated 100 million infections occurring every year. Endemic in the tropical and subtropical areas of the world, dengue fever/dengue hemorrhagic fever (DF/DHF) is emerging as a major public health concern. The complex array of concurrent host physiologic changes has hampered a complete understanding of underlying molecular mechanisms of dengue pathogenesis. Methodology/Principle Findings: Systems level characterization of serum metabolome and lipidome of adult DF patients at early febrile, defervescence, and convalescent stages of DENV infection was performed using liquid chromatography- and gas chromatography-mass spectrometry. The tractability of following metabolite and lipid changes in a relatively large sample size (n = 44) across three prominent infection stages allowed the identification of critical physiologic changes that coincided with the different stages. Sixty differential metabolites were identified in our metabolomics analysis and the main metabolite classes were free fatty acids, acylcarnitines, phospholipids, and amino acids. Major perturbed metabolic pathways included fatty acid biosynthesis and β-oxidation, phospholipid catabolism, steroid hormone pathway, etc., suggesting the multifactorial nature of human host responses. Analysis of phospholipids and sphingolipids verified the temporal trends and revealed association with lymphocytes and platelets numbers. These metabolites were significantly perturbed during the early stages, and normalized to control levels at convalescent stage, suggesting their potential utility as prognostic markers. Conclusions/Significance: DENV infection causes temporally distinct serum metabolome and lipidome changes, and many of the differential metabolites are involved in acute inflammatory responses. Our global analyses revealed early anti-inflammatory responses working in concert to modulate early pro-inflammatory processes, thus preventing the host from development of pathologies by excessive or prolonged inflammation. This study is the first example of how an omic- approach can divulge the extensive, concurrent, and dynamic host responses elicited by DENV and offers plausible physiological insights to why DF is self limiting. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
22. ChemInform Abstract: Graphene Oxide Protected Nucleic Acid Probes for Bioanalysis and Biomedicine.
- Author
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Cui, Liang, Song, Yanling, Ke, Guoliang, Guan, Zhichao, Zhang, Huimin, Lin, Ya, Huang, Yishun, Zhu, Zhi, and Yang, Chaoyong James
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GRAPHENE oxide , *NUCLEIC acid probes , *PHARMACEUTICAL chemistry , *VACCINES , *SERUM , *PHARMACOLOGY - Abstract
Review: 91 refs. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
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