226 results on '"Yu Huang"'
Search Results
2. TRIM21 restricts influenza A virus replication by ubiquitination-dependent degradation of M1.
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Lulu Lin, Xingbo Wang, Zhen Chen, Tingjuan Deng, Yan Yan, Weiren Dong, Yu Huang, and Jiyong Zhou
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin ligase, plays a critical role in the host antiviral response. However, the mechanism and antiviral spectrum of TRIM21 in influenza A virus (IAV) remain unclear. Here, we report that TRIM21 inhibits the replication of various IAV subtypes by targeting matrix protein 1 (M1) from H3/H5/H9, but not H1 and H7 M1. Mechanistically, TRIM21 binds to the residue R95 of M1 and facilitates K48 ubiquitination of M1 K242 for proteasome-dependent degradation, leading to the inhibition of H3, H5, and H9 IAV replication. Interestingly, the recombinant viruses with M1 R95K or K242R mutations were resistance to TRIM21 and exhibited more robust replication and severe pathogenicity. Moreover, the amino acid sequence M1 proteins, mainly from avian influenza such as H5N1, H7N9, H9N2, ranging from 1918 to 2022, reveals a gradual dominant accumulation of the TRIM21-driven R95K mutation when the virus jumps into mammals. Thus, TRIM21 in mammals' functions as a host restriction factor and drives a host adaptive mutation of influenza A virus.
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- 2023
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3. Characterization of the genesis and spatial variability in tectonic fractures in the Gaosong ore field (South China)
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Yulin Pan, Chunzhong Ni, Jianwei Fan, Rongsen Yang, Xiaodong Han, and Yu Huang
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Medicine ,Science - Published
- 2023
4. SERINC5 restricts influenza virus infectivity.
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Fei Zhao, Fengwen Xu, Xiaoman Liu, Yamei Hu, Liang Wei, Zhangling Fan, Liming Wang, Yu Huang, Shan Mei, Li Guo, Long Yang, Shan Cen, Jianwei Wang, Chen Liang, and Fei Guo
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
SERINC5 is a multi-span transmembrane protein that is incorporated into HIV-1 particles in producing cells and inhibits HIV-1 entry. Multiple retroviruses like HIV-1, equine infectious anemia virus and murine leukemia virus are subject to SERINC5 inhibition, while HIV-1 pseudotyped with envelope glycoproteins of vesicular stomatitis virus and Ebola virus are resistant to SERINC5. The antiviral spectrum and the underlying mechanisms of SERINC5 restriction are not completely understood. Here we show that SERINC5 inhibits influenza A virus infection by targeting virus-cell membrane fusion at an early step of infection. Further results show that different influenza hemagglutinin (HA) subtypes exhibit diverse sensitivities to SERINC5 restriction. Analysis of the amino acid sequences of influenza HA1 strains indicates that HA glycosylation sites correlate with the sensitivity of influenza HA to SERINC5, and the inhibitory effect of SERINC5 was lost when certain HA glycosylation sites were mutated. Our study not only expands the antiviral spectrum of SERINC5, but also reveals the role of viral envelope glycosylation in resisting SERINC5 restriction.
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- 2022
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5. MxB inhibits long interspersed element type 1 retrotransposition
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Yu Huang, Fengwen Xu, Shan Mei, Xiaoman Liu, Fei Zhao, Liang Wei, Zhangling Fan, Yamei Hu, Liming Wang, Bin Ai, Shan Cen, Chen Liang, and Fei Guo
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Genetics ,QH426-470 - Abstract
Long interspersed element type 1 (LINE-1, also L1 for short) is the only autonomously transposable element in the human genome. Its insertion into a new genomic site may disrupt the function of genes, potentially causing genetic diseases. Cells have thus evolved a battery of mechanisms to tightly control LINE-1 activity. Here, we report that a cellular antiviral protein, myxovirus resistance protein B (MxB), restricts the mobilization of LINE-1. This function of MxB requires the nuclear localization signal located at its N-terminus, its GTPase activity and its ability to form oligomers. We further found that MxB associates with LINE-1 protein ORF1p and promotes sequestration of ORF1p to G3BP1-containing cytoplasmic granules. Since knockdown of stress granule marker proteins G3BP1 or TIA1 abolishes MxB inhibition of LINE-1, we conclude that MxB engages stress granule components to effectively sequester LINE-1 proteins within the cytoplasmic granules, thus hindering LINE-1 from accessing the nucleus to complete retrotransposition. Thus, MxB protein provides one mechanism for cells to control the mobility of retroelements. Author summary Retrotransposons occupy more than 40% of human genome, and have co-evolved with humans for millions of years. Long interspersed element type 1 (LINE-1, or L1) is the only retrotransposon that is able to jump to a new locus. LINE-1 retrotransposition causes genome instability, and is associated with genetic diseases including autoimmune diseases and cancer. To suppress this genome toxicity caused by LINE-1, humans have developed multi-layered mechanisms to control LINE-1 activity. MxB has been previously shown to inhibit LINE-1 mobility, thus contributing to host restriction of LINE-1. Here, we further demonstrate that MxB effectively restricts LINE-1 retrotransposition by sequestering LINE-1 ribonucleoprotein (RNP) within the cytoplasmic stress granules, thus guards genome stability. Hence our data attribute the restriction function of MxB to sequestering LINE-1 RNP to stress granules.
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- 2022
6. Auxin response factors (ARFs) differentially regulate rice antiviral immune response against rice dwarf virus.
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Qingqing Qin, Guangyao Li, Lian Jin, Yu Huang, Yu Wang, Chunhong Wei, Zhihong Xu, Zhirui Yang, Haiyang Wang, and Yi Li
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
There are 25 auxin response factors (ARFs) in the rice genome, which play critical roles in regulating myriad aspects of plant development, but their role (s) in host antiviral immune defense and the underneath mechanism remain largely unknown. By using the rice-rice dwarf virus (RDV) model system, here we report that auxin signaling enhances rice defense against RDV infection. In turn, RDV infection triggers increased auxin biosynthesis and accumulation in rice, and that treatment with exogenous auxin reduces OsIAA10 protein level, thereby unleashing a group of OsIAA10-interacting OsARFs to mediate downstream antiviral responses. Strikingly, our genetic data showed that loss-of-function mutants of osarf12 or osarf16 exhibit reduced resistance whereas osarf11 mutants display enhanced resistance to RDV. In turn, OsARF12 activates the down-stream OsWRKY13 expression through direct binding to its promoter, loss-of-function mutants of oswrky13 exhibit reduced resistance. These results demonstrated that OsARF 11, 12 and 16 differentially regulate rice antiviral defense. Together with our previous discovery that the viral P2 protein stabilizes OsIAA10 protein via thwarting its interaction with OsTIR1 to enhance viral infection and pathogenesis, our results reveal a novel auxin-IAA10-ARFs-mediated signaling mechanism employed by rice and RDV for defense and counter defense responses.
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- 2020
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7. Quantitation and modeling of post-translational modifications in a therapeutic monoclonal antibody from single- and multiple-dose monkey pharmacokinetic studies using mass spectrometry.
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Xiaobin Xu, Yu Huang, Hao Pan, Rosalynn Molden, Haibo Qiu, Thomas J Daly, and Ning Li
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Medicine ,Science - Abstract
Post-translational modifications (PTMs) of therapeutic monoclonal antibodies (mAbs) are important product quality attributes (PQAs) that can potentially impact drug stability, safety, and efficacy. The PTMs of a mAb may change remarkably in the bloodstream after drug administration compared to in vitro conditions. Thus, monitoring in vivo PTM changes of mAbs helps evaluate the criticality of PQAs during the product risk assessment. In addition, quantitation of the subject exposures to PTM variants helps assess the impact of PTMs on the safety and efficacy of therapeutic mAbs. Here, we developed an immunocapture-liquid chromatography/mass spectrometry (LC/MS) method to quantify in vivo PTM changes a therapeutic mAb overtime in single- and multiple-dose monkey pharmacokinetic (PK) studies. We also built mathematical models to predict the in vivo serum concentrations of PQAs, the subject exposures to PQAs, and the relative abundance of PQAs in single- and multiple-dose regimens. The model predictions are in good agreement with the experimental results. The immunocapture-LC/MS method and mathematical models enable bioanalytical chemists to quantitatively assess the criticality of PQAs during drug development.
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- 2019
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8. Controlling and synchronizing a fractional-order chaotic system using stability theory of a time-varying fractional-order system.
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Yu Huang, Dongfeng Wang, Jinying Zhang, and Feng Guo
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Medicine ,Science - Abstract
Control and synchronization of fractional-order chaotic systems have attracted wide attention due to their numerous potential applications. To get suitable control method and parameters for fractional-order chaotic systems, the stability analysis of time-varying fractional-order systems should be discussed in the first place. Therefore, this paper analyzes the stability of the time-varying fractional-order systems and presents a stability theorem for the system with the order 0
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- 2018
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9. Comparative Transcriptomic Study of Muscle Provides New Insights into the Growth Superiority of a Novel Grouper Hybrid.
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Ying Sun, Yu Huang, Guojun Hu, Xinhui Zhang, Zhiqiang Ruan, Xiaomeng Zhao, Chuanyu Guo, Zhujing Tang, Xiaofeng Li, Xinxin You, Haoran Lin, Yong Zhang, and Qiong Shi
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Medicine ,Science - Abstract
Grouper (Epinephelus spp.) is a group of fish species with great economic importance in Asian countries. A novel hybrid grouper, generated by us and called the Hulong grouper (Hyb), has better growth performance than its parents, E. fuscoguttatus (Efu, ♀) and E. lanceolatus (Ela, ♂). We previously reported that the GH/IGF (growth hormone/insulin-like growth factor) system in the brain and liver contributed to the superior growth of the Hyb. In this study, using transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR), we analyzed RNA expression levels of comprehensive genes in the muscle of the hybrid and its parents. Our data showed that genes involved in glycolysis and calcium signaling in addition to troponins are up-regulated in the Hyb. The results suggested that the activity of the upstream GH/IGF system in the brain and liver, along with the up-regulated glycolytic genes as well as ryanodine receptors (RyRs) and troponins related to the calcium signaling pathway in muscle, led to enhanced growth in the hybrid grouper. Muscle contraction inducing growth could be the major contributor to the growth superiority in our novel hybrid grouper, which may be a common mechanism for hybrid superiority in fishes.
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- 2016
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10. Correction: Angiotensin 1-7 Protects against Angiotensin II-Induced Endoplasmic Reticulum Stress and Endothelial Dysfunction via Mas Receptor.
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Dharmani Murugan, Yeh Siang Lau, Chi Wai Lau, Mohd Rais Mustafa, and Yu Huang
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Medicine ,Science - Published
- 2016
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11. Fully automated whole-head segmentation with improved smoothness and continuity, with theory reviewed.
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Yu Huang and Lucas C Parra
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Medicine ,Science - Abstract
Individualized current-flow models are needed for precise targeting of brain structures using transcranial electrical or magnetic stimulation (TES/TMS). The same is true for current-source reconstruction in electroencephalography and magnetoencephalography (EEG/MEG). The first step in generating such models is to obtain an accurate segmentation of individual head anatomy, including not only brain but also cerebrospinal fluid (CSF), skull and soft tissues, with a field of view (FOV) that covers the whole head. Currently available automated segmentation tools only provide results for brain tissues, have a limited FOV, and do not guarantee continuity and smoothness of tissues, which is crucially important for accurate current-flow estimates. Here we present a tool that addresses these needs. It is based on a rigorous Bayesian inference framework that combines image intensity model, anatomical prior (atlas) and morphological constraints using Markov random fields (MRF). The method is evaluated on 20 simulated and 8 real head volumes acquired with magnetic resonance imaging (MRI) at 1 mm3 resolution. We find improved surface smoothness and continuity as compared to the segmentation algorithms currently implemented in Statistical Parametric Mapping (SPM). With this tool, accurate and morphologically correct modeling of the whole-head anatomy for individual subjects may now be feasible on a routine basis. Code and data are fully integrated into SPM software tool and are made publicly available. In addition, a review on the MRI segmentation using atlas and the MRF over the last 20 years is also provided, with the general mathematical framework clearly derived.
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- 2015
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12. Role of TRPV1 in the Differentiation of Mouse Embryonic Stem Cells into Cardiomyocytes.
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Yan Qi, Zenghua Qi, Zhichao Li, Chun-Kit Wong, Chun So, Iek-Chi Lo, Yu Huang, Xiaoqiang Yao, and Suk-Ying Tsang
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Medicine ,Science - Abstract
Cytosolic Ca2+ ([Ca2+]i) is an important signal that regulates cardiomyocyte differentiation during cardiogenesis. TRPV1 is a Ca2+-permeable channel that is expressed in cardiomyocytes. In the present study, we utilized mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) as a model to investigate the functional role of TRPV1 in cardiomyocyte differentiation. Induction of embryonic stem cells into cardiomyocytes was achieved using embryoid body (EB)-based differentiation method. Quantitative PCRs showed an increased TRPV1 expression during the differentiation process. In [Ca2+]i measurement study, application of TRPV1 agonists, capsaicin and camphor, elicited a [Ca2+]i rise in mESC-CMs, the effect of which was abolished by TRPV1-shRNA. In functional study, treatment of EBs with TRPV1 antagonists (capsazepine and SB366791) and TRPV1-shRNA reduced the size of the EBs and decreased the percentage of spontaneously beating EBs. TRPV1 antagonists and TRPV1-shRNA also suppressed the expression of cardiomyocyte marker genes, including cardiac actin, c-TnT, c-TnI, and α-MHC. Taken together, this study demonstrated an important functional role of TRPV1 channels in the differentiation of mESCs into cardiomyocytes.
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- 2015
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13. Selenium alleviates porcine nephrotoxicity of ochratoxin A by improving selenoenzyme expression in vitro.
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Fang Gan, Hongxia Xue, Yu Huang, Cuiling Pan, and Kehe Huang
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Medicine ,Science - Abstract
Ochratoxin A (OTA), a mycotoxin, is a potent nephrotoxin in humans and animals. Selenium (Se) is an essential micronutrient for humans and animals, and plays a key role in antioxidant defense. To date, little is known about the effect of Se on OTA-induced nephrotoxicity. In this study, the protective effects of selenomethionine against OTA-induced nephrotoxicity were investigated using the porcine kidney 15 (PK15) cells as a model. The results showed that OTA induced nephrotoxicity in a dose-dependent manner. Se at 0.5, 1, 2 and 4 μM had significant protective effects against OTA-induced nephrotoxicity. Furthermore, selenomethionine enhanced the activity and mRNA and protein expression of glutathione peroxidase 1 (GPx1), mRNA expression of GPx4, and mRNA expression of thioredoxin reductase 1 in the presence and absence of OTA. Among them, promoting effect of selenomethionine on GPx1 was maximal. Knock-down of GPx1 by using a GPx1-specific siRNA eliminated the protective effects of selenomethionine against OTA-induced nephrotoxicity. The results suggest that selenomethionine alleviates OTA-induced nephrotoxicity by improving selenoenzyme expression in PK15 cells. Therefore, selenomethionine supplementation may be an attractive strategy for protecting humans and animals from the risk of kidney damage induced by OTA.
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- 2015
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14. Addition of Berberine to 5-Aminosalicylic Acid for Treatment of Dextran Sulfate Sodium-Induced Chronic Colitis in C57BL/6 Mice.
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Yan-hong Li, Man Zhang, Hai-tao Xiao, Hai-bo Fu, Alan Ho, Cheng-yuan Lin, Yu Huang, Ge Lin, and Zhao-xiang Bian
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Medicine ,Science - Abstract
Ulcerative colitis (UC) is a common chronic remitting disease but without satisfactory treatment. Alternative medicine berberine has received massive attention for its potential in UC treatment. Conventional therapies with the addition of berberine are becoming attractive as novel therapies in UC. In the present study, we investigated the preclinical activity of a conventional oral 5-aminosalicylic acid (5-ASA) therapy plus berberine in experimental colitis. A subclinical dose of 5-ASA (200 mg/kg/day) alone or 5-ASA plus berberine (20 mg/kg/day) was orally administered for 30 days to C57BL/6 mice with colitis induced by three cycles of 2% dextran sulfate sodium (DSS). The disease severity, inflammatory responses, drug accumulation and potential toxicity of colitis mice were examined. The results showed that comparing to 5-ASA alone, 5-ASA plus berberine more potently ameliorated DSS-induced disease severity, colon shortening, and colon histological injury. Further, the up-regulation in mRNA level of colonic TNF-α as well as NFκB and JAK2 phosphorylation caused by DSS were more pronouncedly reversed in animals treated with the combination therapy than those treated with 5-ASA alone. Moreover, the addition of berberine to 5-ASA more significantly inhibited lymphocyte TNF-α secretion of DSS mice than 5-ASA alone. In the meanwhile, no extra drug accumulation or potential toxicity to major organs of colitis mice was observed with this combination treatment. In summary, our studies provide preclinical rationale for the addition of berberine to 5-ASA as a promising therapeutic strategy in clinic by reducing dose of standard therapy.
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- 2015
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15. A Fluorescence-Based Genetic Screen to Study Retinal Degeneration in Drosophila.
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Yu Huang, Jun Xie, and Tao Wang
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Medicine ,Science - Abstract
The Drosophila visual system has been proved to be a powerful genetic model to study eye disease such as retinal degeneration. Here, we describe a genetic method termed "Rh1::GFP ey-flp/hid" that is based on the fluorescence of GFP-tagged major rhodopsin Rh1 in the eyes of living flies and can be used to monitor the integrity of photoreceptor cells. Through combination of this method and ERG recording, we examined a collection of 667 mutants and identified 18 genes that are required for photoreceptor cell maintenance, photoresponse, and rhodopsin synthesis. Our findings demonstrate that this "Rh1::GFP ey-flp/hid" method enables high-throughput F1 genetic screens to rapidly and precisely identify mutations of retinal degeneration.
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- 2015
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16. Plasma membrane mechanical stress activates TRPC5 channels.
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Bing Shen, Ching-On Wong, On-Chai Lau, Theodosia Woo, Suwen Bai, Yu Huang, and Xiaoqiang Yao
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Medicine ,Science - Abstract
Mechanical forces exerted on cells impose stress on the plasma membrane. Cells sense this stress and elicit a mechanoelectric transduction cascade that initiates compensatory mechanisms. Mechanosensitive ion channels in the plasma membrane are responsible for transducing the mechanical signals to electrical signals. However, the mechanisms underlying channel activation in response to mechanical stress remain incompletely understood. Transient Receptor Potential (TRP) channels serve essential functions in several sensory modalities. These channels can also participate in mechanotransduction by either being autonomously sensitive to mechanical perturbation or by coupling to other mechanosensory components of the cell. Here, we investigated the response of a TRP family member, TRPC5, to mechanical stress. Hypoosmolarity triggers Ca2+ influx and cationic conductance through TRPC5. Importantly, for the first time we were able to record the stretch-activated TRPC5 current at single-channel level. The activation threshold for TRPC5 was found to be 240 mOsm for hypoosmotic stress and between -20 and -40 mmHg for pressure applied to membrane patch. In addition, we found that disruption of actin filaments suppresses TRPC5 response to hypoosmotic stress and patch pipette pressure, but does not prevent the activation of TRPC5 by stretch-independent mechanisms, indicating that actin cytoskeleton is an essential transduction component that confers mechanosensitivity to TRPC5. In summary, our findings establish that TRPC5 can be activated at the single-channel level when mechanical stress on the cell reaches a certain threshold.
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- 2015
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17. Parameter estimation of fractional-order chaotic systems by using quantum parallel particle swarm optimization algorithm.
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Yu Huang, Feng Guo, Yongling Li, and Yufeng Liu
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Medicine ,Science - Abstract
Parameter estimation for fractional-order chaotic systems is an important issue in fractional-order chaotic control and synchronization and could be essentially formulated as a multidimensional optimization problem. A novel algorithm called quantum parallel particle swarm optimization (QPPSO) is proposed to solve the parameter estimation for fractional-order chaotic systems. The parallel characteristic of quantum computing is used in QPPSO. This characteristic increases the calculation of each generation exponentially. The behavior of particles in quantum space is restrained by the quantum evolution equation, which consists of the current rotation angle, individual optimal quantum rotation angle, and global optimal quantum rotation angle. Numerical simulation based on several typical fractional-order systems and comparisons with some typical existing algorithms show the effectiveness and efficiency of the proposed algorithm.
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- 2015
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18. Angiotensin 1-7 Protects against Angiotensin II-Induced Endoplasmic Reticulum Stress and Endothelial Dysfunction via Mas Receptor.
- Author
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Dharmani Murugan, Yeh Siang Lau, Chi Wai Lau, Mohd Rais Mustafa, and Yu Huang
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Medicine ,Science - Abstract
Angiotensin 1-7 (Ang 1-7) counter-regulates the cardiovascular actions of angiotensin II (Ang II). The present study investigated the protective effect of Ang 1-7 against Ang II-induced endoplasmic reticulum (ER) stress and endothelial dysfunction. Ex vivo treatment with Ang II (0.5 μM, 24 hours) impaired endothelium-dependent relaxation in mouse aortas; this harmful effect of Ang II was reversed by co-treatment with ER stress inhibitors, l4-phenylbutyric acid (PBA) and tauroursodeoxycholic acid (TUDCA) as well as Ang 1-7. The Mas receptor antagonist, A779, antagonized the effect of Ang 1-7. The elevated mRNA expression of CHOP, Grp78 and ATF4 or protein expression of p-eIF2α and ATF6 (ER stress markers) in Ang II-treated human umbilical vein endothelial cells (HUVECs) and mouse aortas were blunted by co-treatment with Ang 1-7 and the latter effect was reversed by A779. Furthermore, Ang II-induced reduction in both eNOS phosphorylation and NO production was inhibited by Ang 1-7. In addition, Ang 1-7 decreased the levels of ER stress markers and augmented NO production in HUVECs treated with ER stress inducer, tunicamycin. The present study provides new evidence for functional antagonism between the two arms of the renin-angiotensin system in endothelial cells by demonstrating that Ang 1-7 ameliorates Ang II-stimulated ER stress to raise NO bioavailability, and subsequently preserves endothelial function.
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- 2015
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19. Genetic heterogeneity of the β-globin gene in various geographic populations of Yunnan in southwestern China.
- Author
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Jie Zhang, Jing He, Xiao-Hong Zeng, Shi-Jun Ge, Yu Huang, Jie Su, Xue-Mei Ding, Ji-Qing Yang, Yong-Jiu Cao, Hong Chen, Ying-Hong Zhang, and Bao-Sheng Zhu
- Subjects
Medicine ,Science - Abstract
The aim of this study was to investigate the geographic distribution of β-globin gene mutations in different ethnic groups in Yunnan province.From 2004 to 2014, 1,441 subjects with hemoglobin disorders, identified by PCR-reverse dot blot and DNA sequencing, were studied according to ethnicity and geographic origin. Haplotypes were examined among 41 unrelated thalassemia chromosomes.Eighteen β-thalassemia mutations and seven hemoglobin variants were identified for 1,616 alleles in 22 different ethnic groups from all 16 prefecture-level divisions of Yunnan. The prevalence of β-thalassemia was heterogeneous and regionally specific. CD 41-42 (-TCTT) was the most prevalent mutation in the populations of northeastern Yunnan. CD 17 (A>T) was the most common mutation in the populations of southeastern Yunnan, especially for the Zhuang minority, whereas Hb E (CD 26, G>A) was the most prevalent mutation in populations of southwestern Yunnan, especially for the Dai minority. Among the seven types of haplotypes identified, CD 17 (A>T) was mainly linked to haplotype VII (+ - - - - - +) and IVS-II-654 (C>T) was only linked to haplotype I (+ - - - - + +).Our data underline the heterogeneity of β-globin gene mutations in Yunnan. This distribution of β-globin mutations in the geographic regions and ethnic populations provided a detailed ethnic basis and evolutionary view of humans in southern China, which will be beneficial for genetic counseling and prevention strategies.
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- 2015
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20. Overexpression of TRIM24 is associated with the onset and progress of human hepatocellular carcinoma.
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Xiao Liu, Yu Huang, Dinghua Yang, Xianghong Li, Jiankun Liang, Liang Lin, Meng Zhang, Kebo Zhong, Bo Liang, and Jialu Li
- Subjects
Medicine ,Science - Abstract
The survival and colonization of tumor cells at new locations involve a variety of complex genetic, epigenetic, and microenvironmental factors. TRIM24 was originally named transcription intermediary factor 1-alpha (TIF1α), which was associated with cellular proliferation and was an oncogene in tumor development. Here we provide the first evidence of the expression profile and clinicopathological significance of TRIM24 in patients with hepatocellular carcinoma (HCC). Immunohistochemistry was employed to determine the expression level of TRIM24 in HCC tissues and noncancerous liver tissues. Elevated TRIM24 level was found in 61.4% HCC samples (51/83) correlating with AFP (P = 0.036), poor differentiation (P = 0.004), intrahepatic metastasis (P = 0.004), recurrence (P = 0.000006), and shorter tumor-free survival time (P = 0.002). Small interfering RNA induced down-regulation of TRIM24 promoted apoptosis in HCC cell line HepG2. Moreover, western blotting analysis revealed that knockdown of TRIM24 increased the protein levels of p53, Bax, and Caspase-8, and decreased Bcl-2, Survivin, Cyclin D1, and CDK4. Depletion of TRIM24 decreased Snail, Slug, β-catenin, and Vimentin, and increased E-cadherin expression, which suggested the involvement of TRIM24 in EMT. These results indicated that TRIM24 plays an important role in the pathogenesis of human HCC.
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- 2014
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21. Oligosaccharide substrate preferences of human extracellular sulfatase Sulf2 using liquid chromatography-mass spectrometry based glycomics approaches.
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Yu Huang, Yang Mao, Jo Ann Buczek-Thomas, Matthew A Nugent, and Joseph Zaia
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Medicine ,Science - Abstract
Sulfs are extracellular endosulfatases that selectively remove the 6-O-sulfate groups from cell surface heparan sulfate (HS) chain. By altering the sulfation at these particular sites, Sulfs function to remodel HS chains. As a result of the remodeling activity, HSulf2 regulates a multitude of cell-signaling events that depend on interactions between proteins and HS. Previous efforts to characterize the substrate specificity of human Sulfs (HSulfs) focused on the analysis of HS disaccharides and synthetic repeating units. In this study, we characterized the substrate preferences of human HSulf2 using HS oligosaccharides with various lengths and sulfation degrees from several naturally occurring HS sources by applying liquid chromatography mass spectrometry based glycomics methods. The results showed that HSulf2 preferentially digests highly sulfated HS oligosaccharides with zero acetyl groups and this preference is length dependent. In terms of length of oligosaccharides, HSulf2 digestion induced more sulfation decrease on DP6 (DP: degree of polymerization) compared to DP2, DP4 and DP8. In addition, the HSulf2 preferentially digests the oligosaccharide domain located at the non-reducing end (NRE) of the HS and heparin chain. In addition, the HSulf2 digestion products were altered only for specific isomers. HSulf2 treated NRE oligosaccharides also showed greater decrease in cell proliferation than those from internal domains of the HS chain. After further chromatographic separation, we identified the three most preferred unsaturated hexasaccharide for HSulf2.
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- 2014
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22. Suppression of XBP1S mediates high glucose-induced oxidative stress and extracellular matrix synthesis in renal mesangial cell and kidney of diabetic rats.
- Author
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Decui Shao, Jia Liu, Jun Ni, Zhen Wang, Yang Shen, Li Zhou, Yu Huang, Jun Wang, Hong Xue, Wei Zhang, and Limin Lu
- Subjects
Medicine ,Science - Abstract
Recent evidences suggest that endoplasmic reticulum (ER) stress was involved in multi pathological conditions, including diabetic nephropathy (DN). X-box binding protein 1(XBP1), as a key mediator of ER stress, has been proved having the capability of preventing oxidative stress. In this study, we investigated the effects of spliced XBP1 (XBP1S), the dominant active form of XBP1, on high glucose (HG)-induced reactive oxygen species (ROS) production and extracellular matrix (ECM) synthesis in cultured renal mesangial cells (MCs) and renal cortex of STZ-induced diabetic rats. Real time PCR and Western blot were used to evaluate the mRNA and protein levels respectively. Transfection of recombinant adenovirus vector carrying XBP1S gene (Ad-XBP1S) was used to upregulate XBP1S expression. XBP1S siRNA was used to knockdown XBP1S expression. ROS level was detected by dihydroethidium (DHE) fluorescent probe assay. The results showed that HG treatment significantly reduced XBP1S protein and mRNA level in the cultured MCs while no obvious change was observed in unspliced XBP1 (XBP1U). In the mean time, the ROS production, collagen IV and fibronectin expressions were increased. Diphenylene-chloride iodonium (DPI), a NADPH oxidase inhibtor, prevented HG-induced increases in ROS as well as collagen IV and fibronectin expressions. Transfection of Ad-XBP1S reversed HG-induced ROS production and ECM expressions. Knockdown intrinsic XBP1S expression induced increases in ROS production and ECM expressions. Supplementation of supreoxide reversed the inhibitory effect of Ad-XBP1S transfection on ECM synthesis. P47phox was increased in HG-treated MCs. Ad-XBP1S transfection reversed HG-induced p47phox increase while XBP1S knockdown upregulated p47phox expression. In the renal cortex of diabetic rats, the expression of XBP1S was reduced while p47phox, collagen IV and fibronectin expression were elevated. These results suggested that XBP1S pathway of ER stress was involved in HG-induced oxidative stress and ECM synthesis. A downstream target of XBP1S in regulating ROS formation might be NADPH oxidase.
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- 2013
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23. H(2)S inhibits hyperglycemia-induced intrarenal renin-angiotensin system activation via attenuation of reactive oxygen species generation.
- Author
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Hong Xue, Ping Yuan, Jun Ni, Chen Li, Decui Shao, Jia Liu, Yang Shen, Zhen Wang, Li Zhou, Wei Zhang, Yu Huang, Chen Yu, Rui Wang, and Limin Lu
- Subjects
Medicine ,Science - Abstract
Decrease in endogenous hydrogen sulfide (H2S) was reported to participate in the pathogenesis of diabetic nephropathy (DN). This study is aimed at exploring the relationship between the abnormalities in H2S metabolism, hyperglycemia-induced oxidative stress and the activation of intrarenal renin-angiotensin system (RAS). Cultured renal mesangial cells (MCs) and streptozotocin (STZ) induced diabetic rats were used for the studies. The expressions of angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin II (Ang II) type I receptor (AT1), transforming growth factor-β1 (TGF-β1) and collagen IV were measured by real time PCR and Western blot. Reactive oxygen species (ROS) production was assessed by fluorescent probe assays. Cell proliferation was analyzed by 5'-bromo-2'-deoxyuridine incorporation assay. Ang II concentration was measured by an enzyme immunoassay. AGT, ACE and AT1 receptor mRNA levels and Ang II concentration were increased in high glucose (HG) -treated MCs, the cell proliferation rate and the production of TGF-β1 and of collagen IV productions were also increased. The NADPH oxidase inhibitor diphenylenechloride iodonium (DPI) was able to reverse the HG-induced RAS activation and the changes in cell proliferation and collagen synthesis. Supplementation of H2S attenuated HG-induced elevations in ROS and RAS activation. Blockade on H2S biosynthesis from cystathione-γ-lyase (CSE) by DL-propargylglycine (PPG) resulted in effects similar to that of HG treatment. In STZ-induced diabetic rats, the changes in RAS were also reversed by H2S supplementation without affecting blood glucose concentration. These data suggested that the decrease in H2S under hyperglycemic condition leads to an imbalance between oxidative and reductive species. The increased oxidative species results in intrarenal RAS activation, which, in turn, contributes to the pathogenesis of renal dysfunction.
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- 2013
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24. MiR-17 partly promotes hematopoietic cell expansion through augmenting HIF-1α in osteoblasts.
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Yuxia Yang, Wei Ma, Dan Wu, Yu Huang, Hongge Li, Junhua Zou, Yanju Zhang, Meifu Feng, and Jianyuan Luo
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Medicine ,Science - Abstract
BACKGROUND: Hematopoietic stem cell (HSC) regulation is highly dependent on interactions with the marrow microenvironment, of which osteogenic cells play a crucial role. While evidence is accumulating for an important role of intrinsic miR-17 in regulating HSCs and HPCs, whether miR-17 signaling pathways are also necessary in the cell-extrinsic control of hematopoiesis hereto remains poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Using the immortalized clone with the characteristics of osteoblasts, FBMOB-hTERT, in vitro expansion, long-term culture initiating cell (LTC-IC) and non-obese diabetic/severe combined immunodeficient disease (NOD/SCID) mice repopulating cell (SRC) assay revealed that the ectopic expression of miR-17 partly promoted the ability of FBMOB-hTERT to support human cord blood (CB) CD34(+) cell expansion and maintain their multipotency. It also seemed that osteoblastic miR-17 was prone to cause a specific expansion of the erythroid lineage. Conversely, deficient expression of miR-17 partly inhibited the hematopoietic supporting ability of FBMOB-hTERT. We further identified that HIF-1α is responsible for, at least in part, the promoted hematopoietic supporting ability of FBMOB-hTERT caused by miR-17. HIF-1α expression is markedly enhanced in miR-17 overexpressed FBMOB-hTERT upon interaction with CB CD34(+) cells compared to other niche associated factors. More interestingly, the specific erythroid lineage expansion of CB CD34(+) cells caused by osteoblastic miR-17 was abrogated by HIF-1α knock down. CONCLUSION/SIGNIFICANCE: Our data demonstrated that CB CD34(+) cell expansion can be partly promoted by osteoblastic miR-17, and in particular, ectopic miR-17 can cause a specific expansion of the erythroid lineage through augmenting HIF-1α in osteoblasts.
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- 2013
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25. Sarcoplasmic phospholamban protein is involved in the mechanisms of postresuscitation myocardial dysfunction and the cardioprotective effect of nitrite during resuscitation.
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Yu Huang, Qing He, Lei Zhan, and Min Yang
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Medicine ,Science - Abstract
OBJECTIVES: Sarcoplasmic reticulum (SR) Ca(2+)-handling proteins play an important role in myocardial dysfunction after acute ischemia/reperfusion injury. We hypothesized that nitrite would improve postresuscitation myocardial dysfunction by increasing nitric oxide (NO) generation and that the mechanism of this protection is related to the modulation of SR Ca(2+)-handling proteins. METHODS: We conducted a randomized prospective animal study using male Sprague-Dawley rats. Cardiac arrest was induced by intravenous bolus of potassium chloride (40 µg/g). Nitrite (1.2 nmol/g) or placebo was administered when chest compression was started. No cardiac arrest was induced in the sham group. Hemodynamic parameters were monitored invasively for 90 minutes after the return of spontaneous circulation (ROSC). Echocardiogram was performed to evaluate cardiac function. Myocardial samples were harvested 5 minutes and 1 hour after ROSC. RESULTS: Myocardial function was significantly impaired in the nitrite and placebo groups after resuscitation, whereas cardiac function (i.e., ejection fraction and fractional shortening) was significantly greater in the nitrite group than in the placebo group. Nitrite administration increased the level of nitric oxide in the myocardium 5 min after resuscitation compared to the other two groups. The levels of phosphorylated phospholamban (PLB) were decreased after resuscitation, and nitrite increased the phosphorylation of phospholamban compared to the placebo. No significant differences were found in the expression of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) and ryanodine receptors (RyRs). CONCLUSIONS: postresuscitation myocardial dysfunction is associated with the impairment of PLB phosphorylation. Nitrite administered during resuscitation improves postresuscitation myocardial dysfunction by preserving phosphorylated PLB protein during resuscitation.
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- 2013
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26. The determinants for the enzyme activity of human parvovirus B19 phospholipase A2 (PLA2) and its influence on cultured cells.
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Xuefeng Deng, Yanming Dong, Qianhui Yi, Yu Huang, Dan Zhao, Yongbo Yang, Peter Tijssen, Jianming Qiu, Kaiyu Liu, and Yi Li
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Medicine ,Science - Abstract
Human parvovirus B19 (B19V) is the causative agent of erythema infectiosum in humans. B19 infection also causes severe disease manifestations, such as chronic anemia in immunocompromised patients, aplastic crisis in patients with a high turnover rate of red blood cells, and hydrops fetalis in pregnant women. Although a secreted phospholipase A2 (PLA2) motif has been identified in the unique region of the B19V minor capsid protein VP1(VP1u), the determinants for its enzyme activity and its influences on host cells are not well understood. The purpose of this study was to investigate the contribution of the PLA2 motif and other regions of the VP1u to the PLA2 activity, to determine the cellular localization of the VP1u protein, and to examine the effects of VP1u on cellular cytokines. We found that in addition to the critical conserved and non-conserved amino acids within the VP1u PLA2 motif, amino acid residues outside the VP1u PLA2 motif are also important for the PLA2 activity. VP1u and various mutants all revealed a nucleo-cytoplasmic distribution. UT7-Epo cells treated with prokaryotic expressed VP1u or mutant proteins with PLA2 activity released a large amount of free fatty acid (FFA), and the cell morphological change occurred dramatically. However, neither free fatty acid nor cell morphology change occurred for cells treated with the mutants without PLA2 activity. The wild type and the VP1u mutants with the PLA2 activity also activated TNF-α promoter and upregulated the transcription activity of NF-κB in transfected cells. In addition, we found that the amino acids outside the PLA2 domain are critical for the viral PLA2 activity, and that these tested VP1u mutants did not affect the localization of the VP1u protein.
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- 2013
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27. AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to β-adrenergic-induced cardiac hypertrophy.
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Matthew J Spindler, Brian T Burmeister, Yu Huang, Edward C Hsiao, Nathan Salomonis, Mark J Scott, Deepak Srivastava, Graeme K Carnegie, and Bruce R Conklin
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Medicine ,Science - Abstract
A-kinase anchoring proteins (AKAPs) are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA) and D (PKD) and an active Rho-guanine nucleotide exchange factor (Rho-GEF) domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown.To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction.These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy.
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- 2013
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28. Fo Shou San, an ancient Chinese herbal decoction, protects endothelial function through increasing endothelial nitric oxide synthase activity.
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Cathy W C Bi, Li Xu, Xiao Yu Tian, Jian Liu, Ken Y Z Zheng, Chi Wai Lau, David T W Lau, Roy C Y Choi, Tina T X Dong, Yu Huang, and Karl W K Tsim
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Medicine ,Science - Abstract
Fo Shou San (FSS) is an ancient herbal decoction comprised of Chuanxiong Rhizoma (CR; Chuanxiong) and Angelicae Sinensis Radix (ASR; Danggui) in a ratio of 2:3. Previous studies indicate that FSS promotes blood circulation and dissipates blood stasis, thus which is being used widely to treat vascular diseases. Here, we aim to determine the cellular mechanism for the vascular benefit of FSS. The treatment of FSS reversed homocysteine-induced impairment of acetylcholine (ACh)-evoked endothelium-dependent relaxation in aortic rings, isolated from rats. Like radical oxygen species (ROS) scavenger tempol, FSS attenuated homocysteine-stimulated ROS generation in cultured human umbilical vein endothelial cells (HUVECs), and it also stimulated the production of nitric oxide (NO) as measured by fluorescence dye and biochemical assay. In addition, the phosphorylation levels of both Akt kinase and endothelial NO synthases (eNOS) were markedly increased by FSS treatment, which was abolished by an Akt inhibitor triciribine. Likewise, triciribine reversed FSS-induced NO production in HUVECs. Finally, FSS elevated intracellular Ca(2+) levels in HUVECs, and the Ca(2+) chelator BAPTA-AM inhibited the FSS-stimulated eNOS phosphorylation. The present results show that this ancient herbal decoction benefits endothelial function through increased activity of Akt kinase and eNOS; this effect is causally via a rise of intracellular Ca(2+) and a reduction of ROS.
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- 2012
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29. Correction: Role of TRPM2 in HO-Induced Cell Apoptosis in Endothelial Cells.
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Lei Sun, Ho-Yan Yau, Wei-Yan Wong, Ronald A. Li, Yu Huang, and Xiaoqiang Yao
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Medicine ,Science - Published
- 2012
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30. Role of TRPM2 in H(2)O(2)-induced cell apoptosis in endothelial cells.
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Lei Sun, Ho-Yan Yau, Wei-Yan Wong, Ronald A Li, Yu Huang, and Xiaoqiang Yao
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Medicine ,Science - Abstract
Melastatin-like transient receptor potential channel 2 (TRPM2) is an oxidant-sensitive and cationic non-selective channel that is expressed in mammalian vascular endothelium. Here we investigated the functional role of TRPM2 channels in hydrogen peroxide (H(2)O(2))-induced cytosolic Ca(2+) ([Ca(2+)](i)) elavation, whole-cell current increase, and apoptotic cell death in murine heart microvessel endothelial cell line H5V. A TRPM2 blocking antibody (TM2E3), which targets the E3 region near the ion permeation pore of TRPM2, was developed. Treatment of H5V cells with TM2E3 reduced the [Ca(2+)](i) rise and whole-cell current change in response to H(2)O(2). Suppressing TRPM2 expression using TRPM2-specific short hairpin RNA (shRNA) had similar inhibitory effect. H(2)O(2)-induced apoptotic cell death in H5V cells was examined using MTT assay, DNA ladder formation analysis, and DAPI-based nuclear DNA condensation assay. Based on these assays, TM2E3 and TRPM2-specific shRNA both showed protective effect against H(2)O(2)-induced apoptotic cell death. TM2E3 and TRPM2-specific shRNA also protect the cells from tumor necrosis factor (TNF)-α-induced cell death in MTT assay. In contrast, overexpression of TRPM2 in H5V cells resulted in an increased response in [Ca(2+)](i) and whole-cell currents to H(2)O(2). TRPM2 overexpression also aggravated the H(2)O(2)-induced apoptotic cell death. Downstream pathways following TRPM2 activation was examined. Results showed that TRPM2 activity stimulated caspase-8, caspase-9 and caspase-3. These findings strongly suggest that TRPM2 channel mediates cellular Ca(2+) overload in response to H(2)O(2) and contribute to oxidant-induced apoptotic cell death in vascular endothelial cells. Down-regulating endogenous TRPM2 could be a means to protect the vascular endothelial cells from apoptotic cell death.
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- 2012
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31. Differential effects of cystathionine-γ-lyase-dependent vasodilatory H2S in periadventitial vasoregulation of rat and mouse aortas.
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Carolin Köhn, Johanna Schleifenbaum, István András Szijártó, Lajos Markó, Galyna Dubrovska, Yu Huang, and Maik Gollasch
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Medicine ,Science - Abstract
BACKGROUND: Hydrogen sulfide (H(2)S) is a potent vasodilator. However, the complex mechanisms of vasoregulation by H(2)S are not fully understood. We tested the hypotheses that (1) H(2)S exerts vasodilatory effects by opening KCNQ-type voltage-dependent (K(v)) K(+) channels and (2) that H(2)S-producing cystathionine-γ-lyase (CSE) in perivascular adipose tissue plays a major role in this pathway. METHODOLOGY/PRINCIPAL FINDINGS: Wire myography of rat and mouse aortas was used. NaHS and 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADTOH) were used as H(2)S donors. KCNQ-type K(v) channels were blocked by XE991. 4-Propargylglycine (PPG) and ß-cyano-l-alanine (BCA), or 2-(aminooxy)-acetic acid (AOAA) were used as inhibitors of CSE or cystathionine-ß-synthase (CBS), respectively. NaHS and ADTOH produced strong vasorelaxation in rat and mouse aortas, which were abolished by KCNQ channel inhibition with XE991. Perivascular adipose tissue (PVAT) exerted an anticontractile effect in these arteries. CSE inhibition by PPG and BCA reduced this effect in aortas from rats but not from mice. CBS inhibition with AOAA did not inhibit the anticontractile effects of PVAT. XE991, however, almost completely suppressed the anticontractile effects of PVAT in both species. Exogenous l-cysteine, substrate for the endogenous production of H(2)S, induced vasorelaxation only at concentrations >5 mmol/l, an effect unchanged by CSE inhibition. CONCLUSIONS/SIGNFICANCE: Our results demonstrate potent vasorelaxant effects of H(2)S donors in large arteries of both rats and mice, in which XE991-sensitive KCNQ-type channel opening play a pivotal role. CSE-H(2)S seems to modulate the effect of adipocyte-derived relaxing factor in rat but not in mouse aorta. The present study provides novel insight into the interaction of CSE-H(2)S and perivascular adipose tissue. Furthermore, with additional technical advances, a future clinical approach targeting vascular H(2)S/KCNQ pathways to influence states of vascular dysfunction may be possible.
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- 2012
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32. Cajaninstilbene acid relaxes rat renal arteries: roles of Ca2+ antagonism and protein kinase C-dependent mechanism.
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Dong-Mei Zhang, Yong Li, Wai San Cheang, Chi Wai Lau, Shun-Ming Lin, Qian-Lan Zhang, Nan Yao, Ying Wang, Xin Wu, Yu Huang, and Wen-Cai Ye
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Medicine ,Science - Abstract
Cajaninstilbene acid (CSA) is a major active component present in the leaves of Cajanus cajan (L.) Millsp. The present study explores the underlying cellular mechanisms for CSA-induced relaxation in rat renal arteries. Vascular reactivity was examined in arterial rings that were suspended in a Multi Myograph System and the expression of signaling proteins was assessed by Western blotting method. CSA (0.1-10 µM) produced relaxations in rings pre-contracted by phenylephrine, serotonin, 9, 11-dideoxy-9α, 11α-epoxymethanoprostaglandin F(2α) (U46619), and 60 mM KCl. CSA-induced relaxations did not show difference between genders and were unaffected by endothelium denudation, nor by treatment with N(G)-nitro-L-arginine methyl ester, indomethacin, ICI-182780, tetraethylammonium ion, BaCl(2), glibenclamide, 4-aminopyridine or propranolol. CSA reduced contraction induced by CaCl(2) (0.01-5 mM) in Ca(2+)-free 60 mM KCl solution and by 30 nM (-)-Bay K8644 in 15 mM KCl solution. CSA inhibited 60 mM KCl-induced Ca(2+) influx in smooth muscle of renal arteries. In addition, CSA inhibited contraction evoked by phorbol 12-myristate 13-acetate (PMA, protein kinase C agonist) in Ca(2+)-free Krebs solution. Moreover, CSA reduced the U46619- and PMA-induced phosphorylation of myosin light chain (MLC) at Ser19 and myosin phosphatase target subunit 1 (MYPT1) at Thr853 which was associated with vasoconstriction. CSA also lowered the phosphorylation of protein kinase C (PKCδ) at Thr505. In summary, the present results suggest that CSA relaxes renal arteries in vitro via multiple cellular mechanisms involving partial inhibition of calcium entry via nifedipine-sensitive calcium channels, protein kinase C and Rho kinase.
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- 2012
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33. Elevated miR-499 levels blunt the cardiac stress response.
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Joseph T C Shieh, Yu Huang, Jacqueline Gilmore, and Deepak Srivastava
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Medicine ,Science - Abstract
BackgroundThe heart responds to myriad stresses by well-described transcriptional responses that involve long-term changes in gene expression as well as more immediate, transient adaptations. MicroRNAs quantitatively regulate mRNAs and thus may affect the cardiac transcriptional output and cardiac function. Here we investigate miR-499, a microRNA embedded within a ventricular-specific myosin heavy chain gene, which is expressed in heart and skeletal muscle.Methodology/principal findingsWe assessed miR-499 expression in human tissue to confirm its potential relevance to human cardiac gene regulation. Using a transgenic mouse model, we found that elevated miR-499 levels caused cellular hypertrophy and cardiac dysfunction in a dose-dependent manner. Global gene expression profiling revealed altered levels of the immediate early stress response genes (Egr1, Egr2 and Fos), ß-myosin heavy chain (Myh7), and skeletal muscle actin (Acta1). We verified the effect of miR-499 on the immediate early response genes by miR-499 gain- and loss-of-function in vitro. Consistent with a role for miR-499 in blunting the response to cardiac stress, asymptomatic miR-499-expressing mice had an impaired response to pressure overload and accentuated cardiac dysfunction.ConclusionsElevated miR-499 levels affect cardiac gene expression and predispose to cardiac stress-induced dysfunction. miR-499 may titrate the cardiac response to stress in part by regulating the immediate early gene response.
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- 2011
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34. Inhibition of renin-angiotensin system reverses endothelial dysfunction and oxidative stress in estrogen deficient rats.
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Lai Ming Yung, Wing Tak Wong, Xiao Yu Tian, Fung Ping Leung, Lai Hang Yung, Zhen Yu Chen, Xiaoqiang Yao, Chi Wai Lau, and Yu Huang
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Medicine ,Science - Abstract
BackgroundEstrogen deficiency increases the cardiovascular risks in postmenopausal women. Inhibition of the renin-angiotensin system (RAS) and associated oxidative stress confers a cardiovascular protection, but the role of RAS in estrogen deficiency-related vascular dysfunction is unclear. The present study investigates whether the up-regulation of RAS and associated oxidative stress contributes to the development of endothelial dysfunction during estrogen deficiency in ovariectomized (OVX) rats.Methodology/principal findingsAdult female rats were ovariectomized with and without chronic treatment with valsartan and enalapril. Isometric force measurement was performed in isolated aortae. The expression of RAS components was determined by immunohistochemistry and Western blotting method while ROS accumulation in the vascular wall was evaluated by dihydroethidium fluorescence. Ovariectomy increased the expression of angiotensin-converting enzyme (ACE), angiotensin II type 1 receptor (AT(1)R), NAD(P)H oxidase, and nitrotyrosine in the rat aorta. An over-production of angiotensin II and ROS was accompanied by decreased phosphorylation of eNOS at Ser(1177) in OVX rat aortae. These pathophysiological changes were closely coupled with increased oxidative stress and decreased nitric oxide bioavailability, culminating in markedly impaired endothelium-dependent relaxations. Furthermore, endothelial dysfunction and increased oxidative stress in aortae of OVX rats were inhibited or reversed by chronic RAS inhibition with enalapril or valsartan.Conclusions/significanceThe novel findings highlight a significant therapeutic benefit of RAS blockade in the treatment of endothelial dysfunction-related vascular complications in postmenopausal states.
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- 2011
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35. Effect of hydrogen peroxide and superoxide anions on cytosolic Ca2+: comparison of endothelial cells from large-sized and small-sized arteries.
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Lei Sun, Ho-Yan Yau, On-Chai Lau, Yu Huang, and Xiaoqiang Yao
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Medicine ,Science - Abstract
We compared the Ca(2+) responses to reactive oxygen species (ROS) between mouse endothelial cells derived from large-sized arteries, aortas (aortic ECs), and small-sized arteries, mesenteric arteries (MAECs). Application of hydrogen peroxide (H(2)O(2)) caused an increase in cytosolic Ca(2+) levels ([Ca(2+)](i)) in both cell types. The [Ca(2+)](i) rises diminished in the presence of U73122, a phospholipase C inhibitor, or Xestospongin C (XeC), an inhibitor for inositol-1,4,5-trisphosphate (IP(3)) receptors. Removal of Ca(2+) from the bath also decreased the [Ca(2+)](i) rises in response to H(2)O(2). In addition, treatment of endothelial cells with H(2)O(2) reduced the [Ca(2+)](i) responses to subsequent challenge of ATP. The decreased [Ca(2+)](i) responses to ATP were resulted from a pre-depletion of intracellular Ca(2+) stores by H(2)O(2). Interestingly, we also found that Ca(2+) store depletion was more sensitive to H(2)O(2) treatment in endothelial cells of mesenteric arteries than those of aortas. Hypoxanthine-xanthine oxidase (HX-XO) was also found to induce [Ca(2+)](i) rises in both types of endothelial cells, the effect of which was mediated by superoxide anions and H(2)O(2) but not by hydroxyl radical. H(2)O(2) contribution in HX-XO-induced [Ca(2+)](i) rises were more significant in endothelial cells from mesenteric arteries than those from aortas. In summary, H(2)O(2) could induce store Ca(2+) release via phospholipase C-IP(3) pathway in endothelial cells. Resultant emptying of intracellular Ca(2+) stores contributed to the reduced [Ca(2+)](i) responses to subsequent ATP challenge. The [Ca(2+)](i) responses were more sensitive to H(2)O(2) in endothelial cells of small-sized arteries than those of large-sized arteries.
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- 2011
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36. Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity.
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Justin Wai-Chung Leung, Wing Tak Wong, Hon Wai Koon, Fong Ming Mo, Sidney Tam, Yu Huang, Paul M Vanhoutte, Stephen Sum Man Chung, and Sookja Kim Chung
- Subjects
Medicine ,Science - Abstract
Endothelin-1 (ET-1) is a potent vasoconstrictor involved in the regulation of vascular tone and implicated in hypertension. However, the role of small blood vessels endothelial ET-1 in hypertension remains unclear. The present study investigated the effect of chronic over-expression of endothelial ET-1 on arterial blood pressure and vascular reactivity using transgenic mice approach. Transgenic mice (TET-1) with endothelial ET-1 over-expression showed increased in ET-1 level in the endothelial cells of small pulmonary blood vessels. Although TET-1 mice appeared normal, they developed mild hypertension which was normalized by the ET(A) receptor (BQ123) but not by ET(B) receptor (BQ788) antagonist. Tail-cuff measurements showed a significant elevation of systolic and mean blood pressure in conscious TET-1 mice. The mice also exhibited left ventricular hypertrophy and left axis deviation in electrocardiogram, suggesting an increased peripheral resistance. The ionic concentrations in the urine and serum were normal in 8-week old TET-1 mice, indicating that the systemic hypertension was independent of renal function, although, higher serum urea levels suggested the occurrence of kidney dysfunction. The vascular reactivity of the aorta and the mesenteric artery was altered in the TET-1 mice indicating that chronic endothelial ET-1 up-regulation leads to vascular tone imbalance in both conduit and resistance arteries. These findings provide evidence for the role of spatial expression of ET-1 in the endothelium contributing to mild hypertension was mediated by ET(A) receptors. The results also suggest that chronic endothelial ET-1 over-expression affects both cardiac and vascular functions, which, at least in part, causes blood pressure elevation.
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- 2011
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37. Cyclic nucleotide-gated channels contribute to thromboxane A2-induced contraction of rat small mesenteric arteries.
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Yuk Ki Leung, Juan Du, Yu Huang, and Xiaoqiang Yao
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Medicine ,Science - Abstract
BACKGROUND: Thromboxane A(2) (TxA(2))-induced smooth muscle contraction has been implicated in cardiovascular, renal and respiratory diseases. This contraction can be partly attributed to TxA(2)-induced Ca(2+) influx, which resulted in vascular contraction via Ca(2+)-calmodulin-MLCK pathway. This study aims to identify the channels that mediate TxA(2)-induced Ca(2+) influx in vascular smooth muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: Application of U-46619, a thromboxane A(2) mimic, resulted in a constriction in endothelium-denuded small mesenteric artery segments. The constriction relies on the presence of extracellular Ca(2+), because removal of extracellular Ca(2+) abolished the constriction. This constriction was partially inhibited by an L-type Ca(2+) channel inhibitor nifedipine (0.5-1 microM). The remaining component was inhibited by L-cis-diltiazem, a selective inhibitor for CNG channels, in a dose-dependent manner. Another CNG channel blocker LY83583 [6-(phenylamino)-5,8-quinolinedione] had similar effect. In the primary cultured smooth muscle cells derived from rat aorta, application of U46619 (100 nM) induced a rise in cytosolic Ca(2+) ([Ca(2+)](i)), which was inhibited by L-cis-diltiazem. Immunoblot experiments confirmed the presence of CNGA2 protein in vascular smooth muscle cells. CONCLUSIONS/SIGNIFICANCE: These data suggest a functional role of CNG channels in U-46619-induced Ca(2+) influx and contraction of smooth muscle cells.
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- 2010
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38. Correction: Prospective Validation of the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) Score for Necrotizing Fasciitis of the Extremities
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Cheng-Ting Hsiao, Chia-Peng Chang, Tsung-Yu Huang, Yi-Chuan Chen, and Wen-Chih Fann
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Multidisciplinary - Published
- 2022
39. Comprehensive analysis of an immune infiltrate-related competitive endogenous RNA network reveals potential prognostic biomarkers for non-small cell lung cancer
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Lizhu Lin, Leihao Hu, Wei Guo, Cai-Zhi Yang, Jietao Lin, Shan Liu, Zhong-Yu Huang, Li Deng, Hong-Xing Yang, Xi Xiao, and Lingling Sun
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Male ,Lung Neoplasms ,Epidemiology ,medicine.medical_treatment ,medicine.disease_cause ,Biochemistry ,Lung and Intrathoracic Tumors ,Mathematical and Statistical Techniques ,Carcinoma, Non-Small-Cell Lung ,Medicine and Health Sciences ,Gene Regulatory Networks ,Multidisciplinary ,MiRTarBase ,Cancer Risk Factors ,Statistics ,Middle Aged ,Prognosis ,Survival Rate ,Nucleic acids ,Oncology ,Area Under Curve ,Long non-coding RNA ,Physical Sciences ,Regression Analysis ,Medicine ,Female ,RNA, Long Noncoding ,Network Analysis ,Research Article ,medicine.drug ,Computer and Information Sciences ,Science ,Antineoplastic Agents ,Biology ,Research and Analysis Methods ,Gefitinib ,Diagnostic Medicine ,microRNA ,Biomarkers, Tumor ,Genetics ,medicine ,Humans ,RNA, Messenger ,Statistical Methods ,Non-coding RNA ,Lung cancer ,Survival analysis ,Aged ,Proportional Hazards Models ,Natural antisense transcripts ,Biology and life sciences ,Competing endogenous RNA ,Cancers and Neoplasms ,Immunotherapy ,medicine.disease ,Non-Small Cell Lung Cancer ,Gene regulation ,MicroRNAs ,ROC Curve ,Drug Resistance, Neoplasm ,Medical Risk Factors ,Cancer research ,RNA ,Gene expression ,Carcinogenesis ,Mathematics - Abstract
Globally, non-small cell lung cancer (NSCLC) is the most common malignancy and its prognosis remains poor because of the lack of reliable early diagnostic biomarkers. The competitive endogenous RNA (ceRNA) network plays an important role in the tumorigenesis and prognosis of NSCLC. Tumor immune microenvironment (TIME) is valuable for predicting the response to immunotherapy and determining the prognosis of NSCLC patients. To understand the TIME-related ceRNA network, the RNA profiling datasets from the Genotype-Tissue Expression and The Cancer Genome Atlas databases were analyzed to identify the mRNAs, microRNAs, and lncRNAs associated with the differentially expressed genes. Weighted gene co-expression network analysis revealed that the brown module of mRNAs and the turquoise module of lncRNAs were the most important. Interactions among microRNAs, lncRNAs, and mRNAs were prognosticated using miRcode, miRDB, TargetScan, miRTarBase, and starBase databases. A prognostic model consisting of 13 mRNAs was established using univariate and multivariate Cox regression analyses and validated by the receiver operating characteristic (ROC) curve. The 22 immune infiltrating cell types were analyzed using the CIBERSORT algorithm, and results showed that the high-risk score of this model was related to poor prognosis and an immunosuppressive TIME. A lncRNA–miRNA–mRNA ceRNA network that included 69 differentially expressed lncRNAs (DElncRNAs) was constructed based on the five mRNAs obtained from the prognostic model. ROC survival analysis further showed that the seven DElncRNAs had a substantial prognostic value for the overall survival (OS) in NSCLC patients; the area under the curve was 0.65. In addition, the high-risk group showed drug resistance to several chemotherapeutic and targeted drugs including cisplatin, paclitaxel, docetaxel, gemcitabine, and gefitinib. The differential expression of five mRNAs and seven lncRNAs in the ceRNA network was supported by the results of the HPA database and RT-qPCR analyses. This comprehensive analysis of a ceRNA network identified a set of biomarkers for prognosis and TIME prediction in NSCLC.
- Published
- 2021
40. Gender differences in trends of bladder cancer mortality-to-incidence ratios according to health expenditure in 55 countries
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Wen-Wei Sung, Shao-Chuan Wang, Lung Chan, Sung-Lang Chen, Tzuo-Yi Hsieh, and Cheng-Yu Huang
- Subjects
Male ,Databases, Factual ,Epidemiology ,Economics ,Cancer Treatment ,030232 urology & nephrology ,Social Sciences ,Global Health ,Database and Informatics Methods ,0302 clinical medicine ,Epidemiology of cancer ,Medicine and Health Sciences ,Genitourinary Cancers ,Data Management ,Multidisciplinary ,integumentary system ,Cancer Risk Factors ,Incidence ,Mortality rate ,Incidence (epidemiology) ,Bladder Cancer ,Oncology ,030220 oncology & carcinogenesis ,Cohort ,Medicine ,Female ,Cancer Epidemiology ,Research Article ,medicine.medical_specialty ,Death Rates ,Urology ,Gross Domestic Product ,Science ,Urinary Bladder ,Health Informatics ,Research and Analysis Methods ,World Health Organization ,03 medical and health sciences ,Health Economics ,Rare Diseases ,Sex Factors ,Population Metrics ,medicine ,Humans ,Human Development Index ,Healthcare Disparities ,Rank correlation ,Bladder cancer ,Population Biology ,business.industry ,Cancers and Neoplasms ,Biology and Life Sciences ,medicine.disease ,Economic Analysis ,Health Care ,Genitourinary Tract Tumors ,Urinary Bladder Neoplasms ,Medical Risk Factors ,Health Expenditures ,business ,Demography - Abstract
The association between bladder cancer mortality-to-incidence ratios (MIRs) and healthcare disparities has gender differences. However, no evidence supports gender as an issue in the association between changes in the MIR and health expenditures on bladder cancer. Changes in the MIR were defined as the difference in data from the years 2012 and 2018, which was named δMIR. Current health expenditures (CHE) and the human development index (HDI) were obtained from the World Health Organization and the Human Development Report Office. The association between variables was analyzed by Spearman’s rank correlation coefficient. In total, 55 countries were analyzed according to data quality and the exclusion of missing data. Globally, the MIR changed according to the HDI level in both genders. Among the 55 countries studied, a high HDI and CHE were significantly associated with a favorable age-standardized rate-based MIR (ASR-based MIR) in both genders and the subgroups according to gender (for both genders, MIR vs. HDI: ρ = -0.720, p < 0.001; MIR vs. CHE per capita: ρ = -0.760, p < 0.001; MIR vs. CHE as a percentage of gross domestic product (CHE/GDP): ρ = -0.663, p < 0.001). Importantly, in females only, the CHE/GDP but neither the HDI score nor the CHE per capita was significantly associated with a favorable ASR-based δMIR (ASR-based δMIR vs. CHE/GDP: ρ = 0.414, p = 0.002). In the gender subgroups, the association between the HDI and the CHE was statistically significant for females and less significant for males. In conclusion, favorable bladder ASR-based MIRs were associated with a high CHE; however, improvement of the ASR-based δMIR data was more correlated with the CHE in females. Further investigation of the gender differences via a cohort survey with detailed information of clinical-pathological characteristics, treatment strategies, and outcomes might clarify these issues and improve therapeutic and/or screening strategies for bladder cancer.
- Published
- 2021
41. Relationships between depression and anxiety symptoms and adipocyte-derived proteins in postmenopausal women
- Author
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Chew-Teng Kor, Ting-Yu Chen, Po-Te Lin, Hung-Ming Wu, Wan-Yu Huang, Ko-Hung Liu, and Yu-Ting Wu
- Subjects
Leptin ,Hamilton Anxiety Rating Scale ,Physiology ,Peptide Hormones ,Emotions ,Social Sciences ,Anxiety ,Biochemistry ,Body Mass Index ,Endocrinology ,Medical Conditions ,0302 clinical medicine ,Immune Physiology ,Adipocytes ,Medicine and Health Sciences ,Insulin ,Psychology ,Innate Immune System ,030219 obstetrics & reproductive medicine ,Multidisciplinary ,Depression ,Center for Epidemiologic Studies Depression Scale ,Lipids ,Anxiety Disorders ,Body Fluids ,Postmenopause ,Cholesterol ,Blood ,Cytokines ,Medicine ,Female ,Adiponectin ,Anatomy ,medicine.symptom ,hormones, hormone substitutes, and hormone antagonists ,Research Article ,Adult ,medicine.medical_specialty ,Endocrine Disorders ,Science ,Immunology ,Adipokine ,Neuropsychiatric Disorders ,Neuroses ,Blood Plasma ,03 medical and health sciences ,Adipokines ,Internal medicine ,Mental Health and Psychiatry ,Diabetes Mellitus ,medicine ,Humans ,Obesity ,Aged ,Mood Disorders ,business.industry ,Biology and Life Sciences ,Molecular Development ,Hormones ,Cross-Sectional Studies ,Mood ,Immune System ,Metabolic Disorders ,Insulin Resistance ,business ,Body mass index ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Introduction Studies on the association between adiponectin and leptin and anxiety and depression among postmenopausal women are limited. Therefore, the present study specifically evaluates the mutual relationships between adiponectin and leptin and anxiety and depression in postmenopausal women. Participants and design In this cross-sectional study, a total of 190 women aged 40–65 years were enrolled. Depression symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D), and anxiety symptoms were evaluated using the Hamilton Anxiety Rating Scale (HAM-A). Fasting specimens were collected to measure sex hormone, glucose, insulin, and adipokine levels. Multiple linear regression analysis was performed to evaluate the associations between depression and anxiety and adipocyte-derived hormones. Settings The study was performed in a hospital medical center. Results Among 190 enrolled postmenopausal women, Spearman’s rank correlation analysis revealed significant correlations between CES-D and HAM-A (r = 0.715, P < 0.0001), between CES-D and adiponectin (p = 0.009) and leptin (p = 0.015), and between HAM-A and adiponectin (p = 0.01) and leptin (p = 0.001). The subjects with CES-D ≥ 16 and with HAM-A ≥ 18 had higher adiponectin levels than those with CES-D < 16 and HAM-A < 18, respectively. After adjusting for age, body mass index, exercise, alanine amino transferase and parameters of lipid profiles, Log adiponectin levels were found to be significantly associated with both CES-D and HAM-A, and Log leptin levels were only significantly associated with HAM-A. Conclusions The data show that adiponectin and leptin levels are significantly associated with depression and anxiety symptoms. These results suggest that higher adiponectin and lower leptin levels may serve as potential markers related to anxiety and mood in postmenopausal women. More future research that is designed to deal with the important confounders (e.g., population heterogeneity) is needed to investigate comprehensively on these associations.
- Published
- 2021
42. Auxin response factors (ARFs) differentially regulate rice antiviral immune response against rice dwarf virus
- Author
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Lian Jin, Qingqing Qin, Zhirui Yang, Guangyao Li, Zhihong Xu, Chunhong Wei, Yu Huang, Haiyang Wang, Yi Li, and Yu Wang
- Subjects
0106 biological sciences ,Leaves ,Mutant ,Gene Expression ,Plant Science ,01 natural sciences ,Biochemistry ,Contractile Proteins ,Gene Expression Regulation, Plant ,Gene expression ,Plant Immunity ,Plant Hormones ,Biology (General) ,Plant Proteins ,Regulation of gene expression ,chemistry.chemical_classification ,0303 health sciences ,Plant Biochemistry ,Plant Anatomy ,Eukaryota ,food and beverages ,Plants ,Cell biology ,Experimental Organism Systems ,Rice dwarf virus ,Host-Pathogen Interactions ,Engineering and Technology ,Research Article ,QH301-705.5 ,Immunology ,Biology ,Research and Analysis Methods ,Reoviridae ,Microbiology ,Virus ,03 medical and health sciences ,Immune system ,Auxin ,Plant and Algal Models ,Virology ,DNA-binding proteins ,Genetics ,Gene Regulation ,Grasses ,Molecular Biology ,Transcription factor ,030304 developmental biology ,Plant Diseases ,Indoleacetic Acids ,Organisms ,Biology and Life Sciences ,Proteins ,Oryza ,RC581-607 ,biology.organism_classification ,Hormones ,Actins ,Regulatory Proteins ,Cytoskeletal Proteins ,chemistry ,Seedlings ,Signal Processing ,Animal Studies ,Auxins ,Parasitology ,Rice ,Immunologic diseases. Allergy ,010606 plant biology & botany ,Transcription Factors - Abstract
There are 25 auxin response factors (ARFs) in the rice genome, which play critical roles in regulating myriad aspects of plant development, but their role (s) in host antiviral immune defense and the underneath mechanism remain largely unknown. By using the rice-rice dwarf virus (RDV) model system, here we report that auxin signaling enhances rice defense against RDV infection. In turn, RDV infection triggers increased auxin biosynthesis and accumulation in rice, and that treatment with exogenous auxin reduces OsIAA10 protein level, thereby unleashing a group of OsIAA10-interacting OsARFs to mediate downstream antiviral responses. Strikingly, our genetic data showed that loss-of-function mutants of osarf12 or osarf16 exhibit reduced resistance whereas osarf11 mutants display enhanced resistance to RDV. In turn, OsARF12 activates the down-stream OsWRKY13 expression through direct binding to its promoter, loss-of-function mutants of oswrky13 exhibit reduced resistance. These results demonstrated that OsARF 11, 12 and 16 differentially regulate rice antiviral defense. Together with our previous discovery that the viral P2 protein stabilizes OsIAA10 protein via thwarting its interaction with OsTIR1 to enhance viral infection and pathogenesis, our results reveal a novel auxin-IAA10-ARFs-mediated signaling mechanism employed by rice and RDV for defense and counter defense responses., Author summary The phytohormone auxin is often critical for plant growth and orchestrates many developmental processes. Here we find that rice accumulates more auxin upon RDV infection and treatment with exogenous auxin enhances rice tolerance to RDV infection. Auxin treatment reduces the protein level of OsIAA10, thus releasing a group of OsIAA10-interacting OsARFs to mediate downstream antiviral responses. Among the 25 ARFs in the rice genome, their functions on regulation of rice antiviral defense are diversified. Our findings elucidate a novel auxin-OsIAA10-ARFs-mediated signaling mechanism employed by rice and RDV for defense and counter defense responses. These findings significantly deepen our understanding of virus-host interactions and provide novel targets for molecular breeding (or engineering) rice cultivars resistant to RDV.
- Published
- 2020
43. SPATS2 is positively activated by long noncoding RNA SNHG5 via regulating DNMT3a expression to promote hepatocellular carcinoma progression
- Author
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Jia Yan, Qing Yu Huang, Ya Jun Huang, Chang Shan Wang, and Peng Xia Liu
- Subjects
Apoptosis ,Polymerase Chain Reaction ,Biochemistry ,DNA Methyltransferase 3A ,Epigenesis, Genetic ,Cell Movement ,Medicine and Health Sciences ,DNA methylation ,Multidisciplinary ,Cell Death ,Liver Diseases ,Liver Neoplasms ,Hep G2 Cells ,Chromatin ,Nucleic acids ,Oncology ,Cell Processes ,Long non-coding RNA ,Disease Progression ,Hyperexpression Techniques ,Medicine ,RNA, Long Noncoding ,Epigenetics ,DNA modification ,Chromatin modification ,Research Article ,Chromosome biology ,Cell biology ,Carcinoma, Hepatocellular ,Science ,Blotting, Western ,Gastroenterology and Hepatology ,Transfection ,Research and Analysis Methods ,Gastrointestinal Tumors ,Genetics ,Gene Expression and Vector Techniques ,Humans ,Non-coding RNA ,Molecular Biology Techniques ,Molecular Biology ,Cell Proliferation ,Molecular Biology Assays and Analysis Techniques ,Biology and life sciences ,Carcinoma ,Proteins ,Cancers and Neoplasms ,Hepatocellular Carcinoma ,DNA ,digestive system diseases ,RNA ,Gene expression - Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors with high mortality worldwide. Spermatogenesis-associated serine-rich 2 (SPATS2) could be a novel diagnostic and prognostic biomarker in HCC. However, the regulatory mechanism of SPATS2 in HCC requires further elucidation. Therefore, the study’s objective was to investigate this process in HCC. In this study, we found that SPATS2 is significantly upregulated in HepG2 cells to promote cell growth and migration. SPATS2 is the target transcript of lncRNA SNHG5. SPATS2 positively affects the proliferation and migration of HepG2 cells caused by the higher expression of SNHG5. Mechanistically, we identified that the elevated of SPATS2 was attributed to SNHG5 related hypomethylation of SPATS2. SNHG5 reduced the expression of DNMT3a to suppress the methylation level of SPATS2. Taken together, our results uncover a novel epigenetic regulatory mechanism of lncRNA SNHG5-DNMT3a axis-related SPATS2 expression underlying HCC progression. This may serve as a novel prognostic marker and a promising therapeutic target for the treatment of HCC.
- Published
- 2022
44. Development of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach
- Author
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Yu Jia Chang, Precious Takondwa Makondi, Po-Li Wei, and Chien-Yu Huang
- Subjects
0301 basic medicine ,MMP2 ,Microarrays ,Exosomes ,Biochemistry ,Metastasis ,0302 clinical medicine ,Basic Cancer Research ,Databases, Genetic ,Medicine and Health Sciences ,Gene Regulatory Networks ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Multidisciplinary ,Liver Neoplasms ,Cadherins ,Extracellular Matrix ,Nucleic acids ,Gene Expression Regulation, Neoplastic ,Bioassays and Physiological Analysis ,Oncology ,030220 oncology & carcinogenesis ,Matrix Metalloproteinase 2 ,Medicine ,Cellular Structures and Organelles ,Anatomy ,Colorectal Neoplasms ,Research Article ,Extracellular matrix organization ,Colon ,Science ,Biology ,Research and Analysis Methods ,Exosome ,03 medical and health sciences ,Antigens, CD ,microRNA ,Genetics ,Biomarkers, Tumor ,medicine ,Humans ,Vesicles ,Non-coding RNA ,Colorectal Cancer ,Natural antisense transcripts ,Biology and life sciences ,Models, Genetic ,Kininogens ,Gene Expression Profiling ,Cancers and Neoplasms ,Computational Biology ,Cell Biology ,medicine.disease ,Microvesicles ,Gene regulation ,Gastrointestinal Tract ,Gene expression profiling ,MicroRNAs ,030104 developmental biology ,Cancer research ,RNA ,Gene expression ,Digestive System - Abstract
BackgroundLiver metastases are the major cause of colorectal cancer (CRC)-related deaths. However, there is no reliable clinical predictor for CRC progression to liver metastasis. In this study, we investigated possible predictors (miRNAs and biomarkers) for clinical application.MethodologyThe Gene Expression Omnibus (GEO) datasets GSE49355, GSE41258 and GSE81558 for genes and GSE54088 and GSE56350 for miRNAs were used to identify common differentially expressed genes (DEGs) and miRNAs between primary CRC tissues and liver metastases. The identified miRNAs and their targets from the DEGs were verified in datasets comprising gene, miRNA and miRNA exosome profiles of CRC patients with no distant metastases (M0) and distant metastases (M1); the interaction networks and pathways were also mapped.ResultsThere were 49 upregulated and 13 downregulated DEGs and 16 downregulated and 14 upregulated miRNAs; between the DEGs and miRNA targets, there were five upregulated and four downregulated genes. MiR-20a was strongly correlated with the status of liver metastasis. MiR-20a, miR499a, and miR-576-5p were highly correlated with the metastatic outcomes. MiR-20a was significantly highly expressed in the M1 group. In an analysis of the miRNA target genes, we found that CDH2, KNG1, and MMP2 were correlated with CRC metastasis. We demonstrated a new possible pathway for CRC metastasis: miR-576-5p/F9, miR20a/MMP2, CTSK, MMP3, and miR449a/P2RY14. The regulation of IGF transport and uptake by IGFBPs, extracellular matrix organization, signal transduction and the immune system were the enriched pathways.ConclusionThis model can predict CRC to liver metastases and the pathways involved, which can be clinically applicable.
- Published
- 2019
45. Facile production of chlorophyllides using recombinant CrCLH1 and their cytotoxicity towards multidrug resistant breast cancer cell lines
- Author
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Chih-Hui Yang, Mi-Hsueh Tai, Keng-Shiang Huang, Yi-Ting Wang, Jei-Fu Shaw, Ting-Yu Huang, Yu-Mei Lin, and Yi-Ping Hsiang
- Subjects
Chlorophyll ,Pigments ,0301 basic medicine ,Leaves ,Chloroplasts ,Cancer Treatment ,Plant Science ,law.invention ,0302 clinical medicine ,law ,Breast Tumors ,Medicine and Health Sciences ,Enzyme assays ,Colorimetric assays ,Cytotoxicity ,Materials ,Bioassays and physiological analysis ,MTT assay ,Multidisciplinary ,Chlorophyllides ,Organic Compounds ,Chemistry ,Plant Anatomy ,Drug Resistance, Multiple ,Oncology ,030220 oncology & carcinogenesis ,Physical Sciences ,MCF-7 Cells ,Recombinant DNA ,Medicine ,Female ,Cellular Structures and Organelles ,Cellular Types ,Research Article ,Ethers ,medicine.drug ,Biocompatibility ,Science ,Plant Cell Biology ,Materials Science ,Breast Neoplasms ,03 medical and health sciences ,Plant Cells ,Breast Cancer ,medicine ,Humans ,Doxorubicin ,Cell Proliferation ,Nutrition ,Chromatography ,Organic Pigments ,Ethanol ,Organic Chemistry ,Extraction (chemistry) ,Chemical Compounds ,Biology and Life Sciences ,Cancers and Neoplasms ,Cell Biology ,Diet ,Research and analysis methods ,Multiple drug resistance ,030104 developmental biology ,Drug Resistance, Neoplasm ,Cell culture ,Alcohols ,Biochemical analysis ,T-Lymphocytes, Cytotoxic - Abstract
The purity of chlorophylls plays one of the key role for the production of chlorophyllides. We have designed a facile method for chlorophyll purification by twice solvent extraction. Twice extraction causes the loss of chlorophylls, but the purity of total chlorophylls can be enhanced 182%. Then, the purified chlorophylls can be converted to relatively pure chlorophyllides facilely. The results show that higher purity of chlorophyllides could be obtained when purified chlorophylls (ethanol-hexane extract) was used as starting materials than that of crude chlorophylls (ethanol-only extract). In biocompatibility test, the results showed that the prepared chlorophyllides can be applied as biomaterials. When the prepared chlorophyllides were applied to anticancer tests, they were active both in MCF7 and MDA-MB-231 (multidrug resistant breast cancer cells) cell lines. In addition, the results suggested that the prepared chlorophyllides could be a potential candidate of combination therapy with doxorubicin to breast cancers.
- Published
- 2021
46. Extracellular and intracellular intermittent magnetic-fluid hyperthermia treatment of SK-Hep1 hepatocellular carcinoma cells based on magnetic nanoparticles coated with polystyrene sulfonic acid
- Author
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Wei Chieh Chang, Bo Wei Chen, Hao Ting Huang, Chih Yu Huang, Chia Ling Hsieh, Da-Jeng Yao, Zung-Hang Wei, Ming Shinn Hsu, Shian Ying Sung, Yun Chi He, and Guo Wei Chiu
- Subjects
Cancer Treatment ,Apoptosis ,02 engineering and technology ,0302 clinical medicine ,Medicine and Health Sciences ,Nanotechnology ,Enzyme assays ,Colorimetric assays ,Magnetite Nanoparticles ,Bioassays and physiological analysis ,Staining ,MTT assay ,Multidisciplinary ,Cell Death ,Chemistry ,Physics ,Liver Diseases ,Liver Neoplasms ,Magnetism ,Cell Staining ,Condensed Matter Physics ,021001 nanoscience & nanotechnology ,Oncology ,Cell Processes ,030220 oncology & carcinogenesis ,Physical Sciences ,Engineering and Technology ,Medicine ,0210 nano-technology ,Intracellular ,Research Article ,Superparamagnetism ,Hyperthermia ,Carcinoma, Hepatocellular ,Cell Survival ,Science ,Gastroenterology and Hepatology ,Research and Analysis Methods ,03 medical and health sciences ,Signs and Symptoms ,Cell Line, Tumor ,Gastrointestinal Tumors ,medicine ,Extracellular ,Humans ,Viability assay ,Carcinoma ,Cancers and Neoplasms ,Biology and Life Sciences ,Hyperthermia, Induced ,Hepatocellular Carcinoma ,Cell Biology ,equipment and supplies ,medicine.disease ,Magnetic Fields ,Specimen Preparation and Treatment ,Cell culture ,Biochemical analysis ,Biophysics ,Polystyrenes ,Nanoparticles ,Magnetic nanoparticles ,Clinical Medicine ,human activities - Abstract
The use of magnetic nanoparticles (MNPs) magnetized on applying an alternating magnetic field (AMF) to stimulate the thermal characteristics and to induce tumor apoptosis is a currently active area of research in cancer treatment. In previous work, we developed biocompatible and superparamagnetic polystyrene-sulfonic-acid-coated magnetic nanoparticles (PSS-MNPs) as applications for magnetically labeled cell trapping, but without assessment of treatment effects on tumor diseases. In the present work, we examined PSS-MNP-induced magnetic fluid hyperthermia (MFH) on SK-Hep1 hepatocellular carcinoma (HCC) cells for lethal thermal effects with a self-made AMF system; an adjustable AMF frequency generated a variable intensity of magnetic field and induced MNP relaxation. The extracellular and intracellular MFH treatments on a SK-Hep1 cell line were implemented in vitro; the result indicates that the lethal effects were efficient and caused a significantly decreased cell viability of SK-Hep1 cells. As the PSS-MNP concentration decreased, especially in intracellular MFH treatments, the MFH effects on cells, however, largely decreased through heat spreading to the culture medium. On controlling and decreasing the volume of culture medium, the problem of heat spreading was solved. It can be consequently expected that PSS-MNPs would be a prospective agent for intracellular cancer magnetotherapy.
- Published
- 2021
47. Comparing machine learning with case-control models to identify confirmed dengue cases
- Author
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Yen Jen Oyang, Chun Chieh Yang, Hsieh Cheng Han, Ting Chia Weng, Chih Hen Yu, Ching Chuan Liu, Yen Jung Liu, Ming Hong Chen, Hao Chien Cheng, Chien Hsiang Hu, Chwan-Chuen King, Chun Yu Huang, Tzong Shiann Ho, and Jung Der Wang
- Subjects
RNA viruses ,Male ,Viral Diseases ,Physiology ,RC955-962 ,Dengue virus ,Pathology and Laboratory Medicine ,Logistic regression ,medicine.disease_cause ,computer.software_genre ,Dengue Fever ,Disease Outbreaks ,Dengue fever ,Machine Learning ,Dengue ,Medical Conditions ,Mathematical and Statistical Techniques ,Endocrinology ,Arctic medicine. Tropical medicine ,Chronic Kidney Disease ,Medicine and Health Sciences ,Medicine ,Applied Mathematics ,Simulation and Modeling ,Incidence (epidemiology) ,Statistics ,Middle Aged ,Body Fluids ,Blood ,Infectious Diseases ,Medical Microbiology ,Nephrology ,Viral Pathogens ,Physical Sciences ,Viruses ,Epidemiological Monitoring ,Female ,Public Health ,Pathogens ,Anatomy ,Public aspects of medicine ,RA1-1270 ,Algorithms ,Research Article ,Neglected Tropical Diseases ,Adult ,Computer and Information Sciences ,Adolescent ,Endocrine Disorders ,Research and Analysis Methods ,Machine learning ,Microbiology ,Machine Learning Algorithms ,Young Adult ,Artificial Intelligence ,Renal Diseases ,Diabetes Mellitus ,Humans ,Statistical Methods ,Microbial Pathogens ,Developing Countries ,Aged ,Models, Statistical ,Biology and life sciences ,Flaviviruses ,Receiver operating characteristic ,business.industry ,Organisms ,Public Health, Environmental and Occupational Health ,Odds ratio ,Emergency department ,Dengue Virus ,Tropical Diseases ,medicine.disease ,Confidence interval ,Blood Counts ,Metabolic Disorders ,Case-Control Studies ,Artificial intelligence ,business ,computer ,Mathematics ,Forecasting - Abstract
In recent decades, the global incidence of dengue has increased. Affected countries have responded with more effective surveillance strategies to detect outbreaks early, monitor the trends, and implement prevention and control measures. We have applied newly developed machine learning approaches to identify laboratory-confirmed dengue cases from 4,894 emergency department patients with dengue-like illness (DLI) who received laboratory tests. Among them, 60.11% (2942 cases) were confirmed to have dengue. Using just four input variables [age, body temperature, white blood cells counts (WBCs) and platelets], not only the state-of-the-art deep neural network (DNN) prediction models but also the conventional decision tree (DT) and logistic regression (LR) models delivered performances with receiver operating characteristic (ROC) curves areas under curves (AUCs) of the ranging from 83.75% to 85.87% [for DT, DNN and LR: 84.60% ± 0.03%, 85.87% ± 0.54%, 83.75% ± 0.17%, respectively]. Subgroup analyses found all the models were very sensitive particularly in the pre-epidemic period. Pre-peak sensitivities (, Author summary Identifying dengue cases early is crucial but challenging for healthcare professionals. This challenge is increased during large epidemics and is a particular problem in non-endemic areas with limited experienced staff. To improve dengue diagnosis, we investigated how to exploit machine learning (ML)-based prediction models and identified four key variables [age, fever, white blood cell counts (WBCs), and platelet counts], which are compatible with clinical and epidemiological knowledge. With these variables, the ML prediction models [decision tree (DT), deep neural network (DNN)] and the logistic regression model developed for identifying laboratory-confirmed dengue cases produced areas under curve (AUCs) of the receiver operating characteristic (ROC) curves ranging from 83.75% to 85.87%. This implies that the prediction models may serve as a pivotal component of an integrated dengue surveillance system and they required only a single complete blood count (CBC) examination. The sensitivities, positive prediction values, and accuracies for major risk factors in the two machine learning models were close to those of the regression models. For future applications, the DNN models with superior performance can be employed at epidemic sites with adequate computer facilities, while the DT and regression models with interpretable prediction logic can be employed at sites with limited or no computer facilities. Artificial intelligence and clinical parameters identified from this study may aid when laboratories are overwhelmed, but should never replace laboratory confirmation.
- Published
- 2020
48. The main factors affecting Taiwan’s economic growth rate via dynamic grey relational analysis
- Author
-
Chun-I Chen, Chiung-Yu Huang, Chia-Chin Hsu, and Mu-Lin Chiou
- Subjects
Index (economics) ,Economics ,Macroeconomics ,Social Sciences ,02 engineering and technology ,Grey relational analysis ,Geographical Locations ,Economic Growth ,Statistics ,0202 electrical engineering, electronic engineering, information engineering ,Consumer price index ,050207 economics ,Birth Rate ,Mathematics ,media_common ,Multidisciplinary ,05 social sciences ,Software Engineering ,Per capita income ,Interest rate ,Models, Economic ,Research Design ,Engineering and Technology ,Medicine ,020201 artificial intelligence & image processing ,Economic Development ,Information Technology ,Raw data ,Research Article ,Employment ,Computer and Information Sciences ,Asia ,Relation (database) ,Science ,media_common.quotation_subject ,Taiwan ,Databases ,Development Economics ,Population Metrics ,0502 economics and business ,Lagging ,Preprocessing ,Population Biology ,Biology and Life Sciences ,Birth Rates ,Unemployment ,Labor Economics ,Unemployment Rates ,People and Places - Abstract
Ever since the grey system theory was proposed about 40 years ago, its characteristics such as small samples, few data, and uncertainty have been used for study in the literature with increasingly wider scope. Recent studies on grey relation analysis have included static data analyses, and most of them have adopted initial values with only a relational order. Under the same study conditions, if different data preprocessing methods are used, then the relational order will be ranked differently. This study took Taiwan as the object to explore seven economic indices (birth rate (%), Taiwan’s total population (thousand people), unemployment rate (%), income per capita (USD), weighted average interest rate on deposits (%), Consumer Price Index (CPI), and national income (NI)) and how they affect the economic growth rate. The traditional static grey relational analysis treated the collected data with taking consideration of time effect which is irrational under some circumstance. An innovative dynamic grey relational analysis was carried out by shifting the raw data due to the time leading or lagging effect which is a mean to improve the capability of traditional grey relational analysis. The differences in analyses between static grey relational analysis and dynamic grey relational analysis via different data preprocessing methods were further discussed, finding that different data preprocessing methods generated a new set of relational orders through the latter. Finally, the prosperity index was used to identify the effects of all factors on economic growth (leading, synchronization, and lagging indices).
- Published
- 2020
49. Electrothermal bipolar vessel sealing device (LigaSure™) versus conventional diathermy in laparoscopic myomectomy: A propensity-matched analysis
- Author
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Yi-Chieh Li, Hui-Yu Huang, Lan-Yang Yang, Hsin-Hong Kuo, Yi-Ting Huang, Chin-Jung Wang, and Angel Chao
- Subjects
Blood transfusion ,medicine.medical_treatment ,Blood Loss, Surgical ,lcsh:Medicine ,030230 surgery ,Pathology and Laboratory Medicine ,Vascular Medicine ,Biochemistry ,0302 clinical medicine ,Medicine and Health Sciences ,Reproductive System Procedures ,Laparoscopy ,lcsh:Science ,030219 obstetrics & reproductive medicine ,Multidisciplinary ,Leiomyoma ,medicine.diagnostic_test ,Hematology ,Middle Aged ,Hospitals ,Clinical Laboratory Sciences ,Treatment Outcome ,Uterine Neoplasms ,Cauterization ,Female ,Energy source ,Research Article ,Adult ,medicine.medical_specialty ,Operative Time ,Surgical and Invasive Medical Procedures ,Hemorrhage ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,Uterine Myomectomy ,medicine ,Humans ,Blood Transfusion ,Hemoglobin ,Propensity Score ,Retrospective Studies ,Laparotomy ,Surgical Excision ,Transfusion Medicine ,business.industry ,lcsh:R ,Biology and Life Sciences ,Proteins ,Myoma ,Retrospective cohort study ,Diathermy ,Length of Stay ,medicine.disease ,Myomectomy ,Surgery ,Health Care ,Health Care Facilities ,Propensity score matching ,lcsh:Q ,business - Abstract
The purpose of this study was to compare the safety and efficacy of an electrothermal bipolar vessel sealing device (LigaSure™) and traditional electrical cauterization in laparoscopic myomectomy (LM). A total of 756 patients with symptomatic uterine myomas who underwent LM were reviewed retrospectively. A total of 225 cases of LM using LigaSure™ (LML group) were compared with a control group treated with traditional electrical cauterization (LME group) under propensity-matched analysis. Outcome measures for both groups were compared, such as operative time, blood loss (BL), complications, need for blood transfusion, hospital expenses, and hospital stay. Six subgroups were divided according to main myoma size and energy source. No cases required switching to abdominal myomectomy. The number of myomas removed, BL, need for blood transfusion, and complications were not significantly different, whereas hospital stay was longer in the LME group than in the LML group and total hospital expenses were higher in the LML group (p < 0.001). The overall operation duration was significantly longer in the LML group but was not significantly different for main myoma >10 cm (LML vs LME, 121.58 ± 41.77 vs 121.69 ± 44.95, p = 0.99); this likely reflects the operative efficiency on using LigaSure™ to manage large tumors. Significant linear correlations between myoma weight and operative time and BL were seen in both groups. Conventional diathermy is more effective for small-to-medium myomas. Use of the LigaSure™ was efficient for myomas >10 cm.
- Published
- 2018
50. Staphylococcus aureus biofilm elicits the expansion, activation and polarization of myeloid-derived suppressor cells in vivo and in vitro
- Author
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Pey-Jium Chang, Kuo-Ti Peng, Hsin-Nung Shih, Ching-Chuan Hsieh, Tsung-Yu Huang, Mel S. Lee, and Pei-Chun Chen
- Subjects
0301 basic medicine ,Male ,T-Lymphocytes ,Staphylococcus ,lcsh:Medicine ,medicine.disease_cause ,Pathology and Laboratory Medicine ,T-Lymphocytes, Regulatory ,law.invention ,Mice ,White Blood Cells ,0302 clinical medicine ,Spectrum Analysis Techniques ,law ,Animal Cells ,Medicine and Health Sciences ,Myeloid Cells ,Staphylococcus Aureus ,lcsh:Science ,Cells, Cultured ,Multidisciplinary ,Microscopy, Confocal ,medicine.diagnostic_test ,Chemistry ,Reverse Transcriptase Polymerase Chain Reaction ,T Cells ,Drugs ,Flow Cytometry ,Immunosuppressives ,Bacterial Pathogens ,medicine.anatomical_structure ,Staphylococcus aureus ,Medical Microbiology ,Spectrophotometry ,Cytophotometry ,Pathogens ,Cellular Types ,Research Article ,Immune Cells ,Immunology ,Bone Marrow Cells ,Research and Analysis Methods ,Microbiology ,Flow cytometry ,03 medical and health sciences ,In vivo ,medicine ,Animals ,Animal Models of Disease ,Microbial Pathogens ,Pharmacology ,Blood Cells ,Bacteria ,Macrophages ,lcsh:R ,Biofilm ,Organisms ,Biology and Life Sciences ,Bacteriology ,Cell Biology ,biochemical phenomena, metabolism, and nutrition ,In vitro ,Rats ,Mice, Inbred C57BL ,Animal Models of Infection ,030104 developmental biology ,Biofilms ,Myeloid-derived Suppressor Cell ,Microscopy, Electron, Scanning ,Animal Studies ,Suppressor ,lcsh:Q ,Bone marrow ,Bacterial Biofilms ,030215 immunology - Abstract
Staphylococcus aureus (S. aureus) is one of the most common causes of biofilm infections in periprosthetic joint infections (PJIs). Accumulating evidence has shown that the immunosuppressive environment established by S. aureus biofilm infection in PJIs involves the presence of myeloid-derived suppressor cells (MDSCs) and M2-macrophages. Due to the diversity of MDSCs, little is known about whether S. aureus biofilm preferentially expands specific MDSC subsets or whether MDSCs can further differentiate into M2-macrophages during S. aureus biofilm infection. Here, we show that in agreement with the results from an established rat PJI model, S. aureus biofilm cocultured with freshly isolated bone marrow cells (BMCs) in vitro significantly increases the proportions of MDSCs, total macrophages and M2-macrophages. Interestingly, we find that treatment of the BMCs in vitro with S. aureus biofilm preferentially promotes the expansion of monocytic MDSCs but not granulocytic MDSCs. Biofilm treatment also substantially enhances the overall MDSC immunosuppressive activity in addition to the MDSC expansion in vitro. Importantly, we provide evidence that S. aureus biofilm is capable of further stimulating the conversion of monocytic MDSCs into M2-macrophages in vitro and in vivo. Collectively, our studies reveal a direct link between MDSCs and M2-macrophages occurring in S. aureus-associated PJIs.
- Published
- 2017
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