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Article ; Online: Dysfunction of Nrf2-regulated cellular defence system and JNK activation induced by high dose of fly Ash particles are associated with pulmonary injury in mouse lungs.

Zhang, Jingwen / Liu, Kaihua / Tang, Xiuwen / Wang, Xiu Jun

2024 Volume 275, Page(s) 116239

Abstract: The mechanisms of the exposure to fine particulate matter (PM) as a risk factor for pulmonary injury are not fully understood. The transcription factor, NF-E2-related factor 2 (Nrf2), plays a key role in protection lung against PM insult and cancer ... ...

Abstract	The mechanisms of the exposure to fine particulate matter (PM) as a risk factor for pulmonary injury are not fully understood. The transcription factor, NF-E2-related factor 2 (Nrf2), plays a key role in protection lung against PM insult and cancer chemoprevention. In this study, F3-S fly ash particles from a municipal waste incinerator were evaluated as a PM model. We found that F3-S triggered hierarchical oxidative stress responses involving the prolonged activation of the cytoprotective Nrf2 transcriptional program via Keap1 Cys
MeSH term(s)	Animals ; Mice ; Coal Ash/toxicity ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Kelch-Like ECH-Associated Protein 1/metabolism ; Lung Injury ; Oxidative Stress ; Lung/metabolism
Chemical Substances	Coal Ash ; NF-E2-Related Factor 2 ; Kelch-Like ECH-Associated Protein 1
Language	English
Publishing date	2024-03-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	436536-7
ISSN	1090-2414 ; 0147-6513
ISSN (online)	1090-2414
ISSN	0147-6513
DOI	10.1016/j.ecoenv.2024.116239
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Article ; Online: High-performance state feedback controller for permanent magnet synchronous motor.

Zhang, Bitao / Tang, Xiuwen

ISA transactions

2021 Volume 118, Page(s) 144–158

Abstract: Due to the outstanding characteristics of permanent magnet synchronous motor (PMSM), such as fast response speed, high torque and power density, it has been widely used in the automation industry. However, it remains a challenge to obtain high control ... ...

Abstract	Due to the outstanding characteristics of permanent magnet synchronous motor (PMSM), such as fast response speed, high torque and power density, it has been widely used in the automation industry. However, it remains a challenge to obtain high control performance caused by its dynamic complexity. In order to achieve favorable control performance, a novel state feedback control algorithm and parameter tuning method for permanent magnet synchronous motor is proposed in this paper. The development of the presented control method starts with the analyses of current state-space equation in rotor reference frame and then provides the design procedure of state feedback controller from the first-order to third-order system. An enhanced Proportional-Integral (PI) plus state feedback controller is designed, which includes the information of current, the error of current and the integral of the current error. The stability and convergence of the proposed control approach, as the extension of the conventional PI regulator, is mathematically justified in state feedback theory. The simulation and experimental results compared with the classical state feedback control method illustrate that the proposed PI plus state feedback control scheme can obtain better control performance in the presence of parameter changes and disturbance.
Language	English
Publishing date	2021-02-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2012746-7
ISSN	1879-2022 ; 0019-0578
ISSN (online)	1879-2022
ISSN	0019-0578
DOI	10.1016/j.isatra.2021.02.009
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Article ; Online: REPLY.

Tang, Xiuwen / Wang, Xiu Jun

Hepatology (Baltimore, Md.)

2020 Volume 73, Issue 1, Page(s) 468–469

MeSH term(s)	Carcinoma, Hepatocellular ; Guanine/analogs & derivatives ; Hepatitis B virus ; Humans ; Liver Neoplasms ; Neoplasm Recurrence, Local ; Tenofovir
Chemical Substances	entecavir (5968Y6H45M) ; Guanine (5Z93L87A1R) ; Tenofovir (99YXE507IL)
Language	English
Publishing date	2020-12-07
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.31441
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Article ; Online: Identification of potential biomarkers with colorectal cancer based on bioinformatics analysis and machine learning.

Hammad, Ahmed / Elshaer, Mohamed / Tang, Xiuwen

Mathematical biosciences and engineering : MBE

2021 Volume 18, Issue 6, Page(s) 8997–9015

Abstract: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Biomarker discovery is critical to improve CRC diagnosis, however, machine learning offers a new platform to study the etiology of CRC for this purpose. Therefore, the current ... ...

Abstract	Colorectal cancer (CRC) is one of the most common malignancies worldwide. Biomarker discovery is critical to improve CRC diagnosis, however, machine learning offers a new platform to study the etiology of CRC for this purpose. Therefore, the current study aimed to perform an integrated bioinformatics and machine learning analyses to explore novel biomarkers for CRC prognosis. In this study, we acquired gene expression microarray data from Gene Expression Omnibus (GEO) database. The microarray expressions GSE103512 dataset was downloaded and integrated. Subsequently, differentially expressed genes (DEGs) were identified and functionally analyzed via Gene Ontology (GO) and Kyoto Enrichment of Genes and Genomes (KEGG). Furthermore, protein protein interaction (PPI) network analysis was conducted using the STRING database and Cytoscape software to identify hub genes; however, the hub genes were subjected to Support Vector Machine (SVM), Receiver operating characteristic curve (ROC) and survival analyses to explore their diagnostic values. Meanwhile, TCGA transcriptomics data in Gene Expression Profiling Interactive Analysis (GEPIA) database and the pathology data presented by in the human protein atlas (HPA) database were used to verify our transcriptomic analyses. A total of 105 DEGs were identified in this study. Functional enrichment analysis showed that these genes were significantly enriched in biological processes related to cancer progression. Thereafter, PPI network explored a total of 10 significant hub genes. The ROC curve was used to predict the potential application of biomarkers in CRC diagnosis, with an area under ROC curve (AUC) of these genes exceeding 0.92 suggesting that this risk classifier can discriminate between CRC patients and normal controls. Moreover, the prognostic values of these hub genes were confirmed by survival analyses using different CRC patient cohorts. Our results demonstrated that these 10 differentially expressed hub genes could be used as potential biomarkers for CRC diagnosis.
MeSH term(s)	Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/genetics ; Computational Biology ; Databases, Genetic ; Gene Expression Regulation, Neoplastic ; Humans ; Protein Interaction Maps ; Support Vector Machine
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2021-12-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2265126-3
ISSN	1551-0018 ; 1551-0018
ISSN (online)	1551-0018
ISSN	1551-0018
DOI	10.3934/mbe.2021443
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Article ; Online: Transcriptome analysis of potential candidate genes and molecular pathways in colitis-associated colorectal cancer of Mkp-1-deficient mice.

Hammad, Ahmed / Zheng, Zhao-Hong / Namani, Akhileshwar / Elshaer, Mohamed / Wang, Xiu Jun / Tang, Xiuwen

BMC cancer

2021 Volume 21, Issue 1, Page(s) 607

Abstract: Background: The nuclear phosphatase mitogen-activate protein kinase phosphatase-1 (MKP-1) is a key negative regulator of the innate immune response through the regulation of the biosynthesis of proinflammatory cytokines. In colorectal cancer (CRC), ... ...

Abstract	Background: The nuclear phosphatase mitogen-activate protein kinase phosphatase-1 (MKP-1) is a key negative regulator of the innate immune response through the regulation of the biosynthesis of proinflammatory cytokines. In colorectal cancer (CRC), which is induced mainly by chronic inflammation, Mkp-1 overexpression was found in addition to disturbances in Mkp-1 functions, which may play a role in cancer development in different types of tumors. However, the potential molecular mechanisms by which Mkp-1 influences CRC development is not clear. Here, we performed global gene expression profiling of Mkp-1 KO mice using RNA sequencing (RNA-seq) to explore the role of Mkp-1 in CRC progression using transcriptome analysis. Methods: Azoxymethane/dextran sodium sulfate (AOM/DSS) mouse models were used to examine the most dramatic molecular and signaling changes that occur during different phases of CRC development in wild-type mice and Mkp-1 KO mice. Comprehensive bioinformatics analyses were used to elucidate the molecular processes regulated by Mkp-1. Differentially expressed genes (DEGs) were identified and functionally analyzed by Gene Ontology (GO), Kyoto Enrichment of Genes and Genomes (KEGG). Then, protein-protein interaction (PPI) network analysis was conducted using the STRING database and Cytoscape software. Results: Persistent DEGs were different in adenoma and carcinoma stage (238 & 251, respectively) and in WT and MKp-1 KO mice (221& 196, respectively). Mkp-1 KO modulated key molecular processes typically activated in cancer, in particular, cell adhesion, ion transport, extracellular matrix organization, response to drug, response to hypoxia, and response to toxic substance. It was obvious that these pathways are closely associated with cancer development and metastasis. From the PPI network analyses, nine hub genes associated with CRC were identified. Conclusion: These findings suggest that MKp-1 and its hub genes may play a critical role in cancer development, prognosis, and determining treatment outcomes. We provide clues to build a potential link between Mkp-1 and colitis-associated tumorigenesis and identify areas requiring further investigation.
MeSH term(s)	Animals ; Azoxymethane/administration & dosage ; Azoxymethane/toxicity ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinogenesis/genetics ; Colitis/chemically induced ; Colitis/complications ; Colitis/immunology ; Colitis/pathology ; Colitis-Associated Neoplasms/genetics ; Colitis-Associated Neoplasms/immunology ; Colitis-Associated Neoplasms/pathology ; Computational Biology ; Dextran Sulfate/administration & dosage ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Dual Specificity Phosphatase 1/genetics ; Dual Specificity Phosphatase 1/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mice ; Mice, Knockout ; Prognosis ; Protein Interaction Mapping ; Protein Interaction Maps/genetics ; RNA-Seq ; Signal Transduction/genetics
Chemical Substances	Biomarkers, Tumor ; Dextran Sulfate (9042-14-2) ; Dual Specificity Phosphatase 1 (EC 3.1.3.48) ; Dusp1 protein, mouse (EC 3.1.3.48) ; Azoxymethane (MO0N1J0SEN)
Language	English
Publishing date	2021-05-25
Publishing country	England
Document type	Journal Article
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/s12885-021-08200-0
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Article ; Online: Quinone oxidoreductase 1 is overexpressed in gastric cancer and associated with outcome of adjuvant chemotherapy and survival.

Jiang, Zhi-Nong / Ahmed, Syed Minhaj Uddin / Wang, Qin-Chuan / Shi, Hong-Fei / Tang, Xiu-Wen

World journal of gastroenterology

2021 Volume 27, Issue 22, Page(s) 3085–3096

Abstract: Background: Quinine oxidoreductase 1 (NQO1) plays a vital role in protecting normal cells against oxidative damage and electrophilic attack. It is highly expressed in many solid tumors, suggesting a role in cancer development and progression. However, ... ...

Abstract	Background: Quinine oxidoreductase 1 (NQO1) plays a vital role in protecting normal cells against oxidative damage and electrophilic attack. It is highly expressed in many solid tumors, suggesting a role in cancer development and progression. However, the role of NQO1 in gastric cancer and its effect on cancer development and prognosis have not been fully investigated. Aim: To investigate the clinical relevance of NQO1 protein expression in gastric cancer and to explore the potential of NQO1 to serve as a prognostic biomarker and therapeutic target. Methods: In this retrospective study, gastric cancer specimens of 175 patients who were treated between 1995 and 2011 were subjected to immunohistochemistry analyses for NQO1. The correlation of NQO1 expression with gastric cancer prognosis and clinical and pathological parameters was investigated. Results: NQO1 protein was overexpressed in 59.43% (104/175) of the analyzed samples. Overexpression of NQO1 was associated with a significantly inferior prognosis. In addition, multivariate analysis suggested that NQO1 overexpression, along with tumor stage and patient age, are prominent prognostic biomarkers for gastric cancer. Moreover, NQO1 overexpression was correlated to a better response to 5-fluorouracil (5-FU)-based adjuvant chemotherapy. Conclusion: NQO1 overexpression is associated with a significantly poor prognosis and better response to 5-FU in patients with gastric cancer. These findings are relevant for improving therapeutic approaches for gastric cancer patients.
MeSH term(s)	Chemotherapy, Adjuvant ; Humans ; Kaplan-Meier Estimate ; NAD(P)H Dehydrogenase (Quinone)/genetics ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/drug therapy
Chemical Substances	NAD(P)H Dehydrogenase (Quinone) (EC 1.6.5.2) ; NQO1 protein, human (EC 1.6.5.2)
Language	English
Publishing date	2021-06-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.v27.i22.3085
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Article: Systematic Identification of Multi Omics-based Biomarkers in

Namani, Akhileshwar / Zheng, Zhaohong / Wang, Xiu Jun / Tang, Xiuwen

Journal of Cancer

2019 Volume 10, Issue 27, Page(s) 6813–6821

Abstract: Mutations ... ...

Abstract	Mutations in
Language	English
Publishing date	2019-11-01
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2573318-7
ISSN	1837-9664
ISSN	1837-9664
DOI	10.7150/jca.35489
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Article ; Online: Integrated data analysis reveals significant associations of

Elshaer, Mohamed / ElManawy, Ahmed Islam / Hammad, Ahmed / Namani, Akhileshwar / Wang, Xiu Jun / Tang, Xiuwen

Aging

2020 Volume 12, Issue 8, Page(s) 7183–7206

Abstract: ... ...

Abstract	KEAP1
MeSH term(s)	Adenocarcinoma of Lung/genetics ; Adenocarcinoma of Lung/metabolism ; Adenocarcinoma of Lung/pathology ; Cell Line, Tumor ; DNA Methylation ; DNA Mutational Analysis ; DNA, Neoplasm/genetics ; DNA, Neoplasm/metabolism ; Female ; Humans ; Kelch-Like ECH-Associated Protein 1/biosynthesis ; Kelch-Like ECH-Associated Protein 1/genetics ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Male ; Mutation ; Prognosis ; Signal Transduction
Chemical Substances	DNA, Neoplasm ; KEAP1 protein, human ; Kelch-Like ECH-Associated Protein 1
Language	English
Publishing date	2020-04-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.103068
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Article ; Online: NRF2 has a splicing regulatory function involving the survival of motor neuron (SMN) in non-small cell lung cancer.

Cui, Qinqin / Wang, Wei / Namani, Akhileshwar / Wang, Hongyan / Hammad, Ahmed / Huang, Pu / Gao, Yang / Elshaer, Mohamed / Wu, Yihe / Wang, Xiu Jun / Tang, Xiuwen

Oncogene

2023 Volume 42, Issue 37, Page(s) 2751–2763

Abstract: The nuclear factor erythroid 2-like 2 (NFE2L2; NRF2) signaling pathway is frequently deregulated in human cancers. The critical functions of NRF2, other than its transcriptional activation, in cancers remain largely unknown. Here, we uncovered a ... ...

Abstract	The nuclear factor erythroid 2-like 2 (NFE2L2; NRF2) signaling pathway is frequently deregulated in human cancers. The critical functions of NRF2, other than its transcriptional activation, in cancers remain largely unknown. Here, we uncovered a previously unrecognized role of NRF2 in the regulation of RNA splicing. Global splicing analysis revealed that NRF2 knockdown in non-small cell lung cancer (NSCLC) A549 cells altered 839 alternative splicing (AS) events in 485 genes. Mechanistic studies demonstrated that NRF2 transcriptionally regulated SMN mRNA expression by binding to two antioxidant response elements in the SMN1 promoter. Post-transcriptionally, NRF2 was physically associated with the SMN protein. The Neh2 domain of NRF2, as well as the YG box and the region encoded by exon 7 of SMN, were required for their interaction. NRF2 formed a complex with SMN and Gemin2 in nuclear gems and Cajal bodies. Furthermore, the NRF2-SMN interaction regulated RNA splicing by expressing SMN in NRF2-knockout HeLa cells, reverting some of the altered RNA splicing. Moreover, SMN overexpression was significantly associated with alterations in the NRF2 pathway in patients with lung squamous cell carcinoma from The Cancer Genome Atlas. Taken together, our findings suggest a novel therapeutic strategy for cancers involving an aberrant NRF2 pathway.
MeSH term(s)	Humans ; HeLa Cells ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/metabolism ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; SMN Complex Proteins/genetics ; SMN Complex Proteins/metabolism ; RNA-Binding Proteins/genetics ; Muscular Atrophy, Spinal/genetics ; Muscular Atrophy, Spinal/metabolism ; Muscular Atrophy, Spinal/therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Motor Neurons/metabolism ; RNA Splicing/genetics ; Cyclic AMP Response Element-Binding Protein/metabolism
Chemical Substances	NF-E2-Related Factor 2 ; SMN Complex Proteins ; RNA-Binding Proteins ; Cyclic AMP Response Element-Binding Protein
Language	English
Publishing date	2023-08-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-023-02799-z
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Article: Identification of novel Nrf2 target genes as prognostic biomarkers in colitis-associated colorectal cancer in Nrf2-deficient mice

Hammad, Ahmed / Gao, Yang / Namani, Akhileshwar / Shi, Hong-Fei / Tang, Xiuwen / Zheng, Zhao-Hong

Life sciences. 2019 Dec. 01, v. 238

2019

Abstract: Colorectal cancer (CRC) is the third most common cancer worldwide. Nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of many cytoprotective genes, plays a protective role in carcinogenesis. Recent studies have identified a specific ... ...

Abstract	Colorectal cancer (CRC) is the third most common cancer worldwide. Nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of many cytoprotective genes, plays a protective role in carcinogenesis. Recent studies have identified a specific gene-expression signature regulated by the Nrf2 pathway in lung adenocarcinoma and head-and-neck squamous cell cancer. However, the roles of Nrf2 in the development of colitis-associated colorectal cancer (CACC) have not been well characterized. Nrf2 target genes as prognostic biomarkers in CACC remain to be explored. Thus, this work aimed to identify the molecular changes that occur during mouse CACC progression to facilitate the development of diagnostic and prognostic biomarkers.The CACC model was established using azoxymethane (AOM) with dextran sulfate sodium salt (DSS) in BALB/c mice for 3 weeks to induce colitis-associated adenoma (CAA, early stage) and for 9 weeks to induce colitis-associated carcinoma (CAC, late stage). Using RNA-sequencing and bioinformatics analyses we examined the mRNA expression profiles of 6 groups: wild-type control (WT-C), WT-CAA, WT-CAC, Nrf2 knockout control (Nrf2KO-C), Nrf2KO-CAA, and Nrf2KO-CAC.In the AOM/DSS model of colitis-associated tumorigenesis, Nrf2−/− mice showed a phenotype similar to WT mice, but with significantly more tumors and a much higher percentage of adenocarcinomas. We identified 47 novel Nrf2 genes via gene expression profiling of tumor samples. Survival analysis showed that 23 of these genes were biomarkers of a poor prognosis in colon cancer patients.Nrf2 target genes deserve exploration as prognostic and therapeutic targets for CRC.
Keywords	adenocarcinoma ; adenoma ; azoxymethane ; bioinformatics ; biomarkers ; carcinogenesis ; colorectal neoplasms ; dextran sulfate ; gene expression ; gene expression regulation ; genes ; lungs ; messenger RNA ; mice ; models ; phenotype ; prognosis ; protective effect ; sequence analysis ; squamous cell carcinoma ; therapeutics
Language	English
Dates of publication	2019-1201
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2019.116968
Database	NAL-Catalogue (AGRICOLA)

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