Publications by authors named "Dong-Mei Wu"

145 Publications

Taxonomy and Phylogeny of the Complex With Descriptions of Six New Species From East Asia.

Authors:
Shun Liu Mei-Ling Han Tai-Min Xu Yan Wang Dong-Mei Wu Bao-Kai Cui

Front Microbiol 2021 26;12:644979. Epub 2021 Mar 26.

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing, China.

is a common brown-rot fungal species found in northern hemisphere. It grows on many different gymnosperm and angiosperm trees. Recent studies show that it is a species complex; three species from North America and one species from Europe have been recognized in this complex. In the current study, six new species in the complex were discovered from East Asia, based on morphological characters and phylogenetic analyses inferred from the sequence data of the internal transcribed spacer (ITS) regions, the second subunit of RNA polymerase II (RPB2), and the translation elongation factor 1-α gene (TEF). Detailed descriptions of the six new species are provided. Our results also indicates that species of the complex from East Asia usually have limited distribution areas and host specialization.
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http://dx.doi.org/10.3389/fmicb.2021.644979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034269PMC
March 2021

Development of C60-based labeling reagents for the determination of low-molecular-weight compounds by matrix assisted laser desorption ionization mass spectrometry (II): Determination of thiols in human serum.

Authors:
Zhang-Na Qin Jun Ding Qiong-Wei Yu Chu-Bo Qi Dong-Mei Wu Ping Zhou Yu-Qi Feng

Anal Chim Acta 2020 Apr 16;1105:112-119. Epub 2020 Jan 16.

Department of Chemistry, Wuhan University, Wuhan, 430072, PR China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430072, PR China. Electronic address:

Perturbation of thiol homeostasis in biological fluids are thought to be associated with several diseases, and reliable analytical methods for the determination of low molecular weight (LMW) thiols in human plasma or serum are thus required. In this study, a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method is described for high throughput determination of four LMW thiols (glutathione, cysteine, homocysteine and cysteinylglycine) in human serum. It is based on the use of a bromoacetyl functionalized C60 (Br-C60) as a derivatization reagent to label thiols. The Br-C60 labeling can add an 832-Da tag to thiols, which moves thiol signals to high mass region and effectively avoids the signal interference generated by the traditional MALDI matrix below 800 Da. The labeling can be completed within 5 min under microwave-assisted condition. Thereby, the Br-C60 labeling based MALDI-TOF MS analytical method can achieve high throughput analysis of LMW thiols in serum. Good linearities of the method for the thiols in human serum were obtained in the range of 0.5-500.0 μM with correlation coefficient (R) greater than 0.9960. The limit of detection is in the range of 0.07-0.18 μM for the investigated thiols in human serum with relative standard deviations of lower than 13.5% and recoveries ranging from 81.9 to 117.1%. Using the method, four thiols in microliter serum samples of breast cancer (BC) patients were determined. The result showed that the contents of the four thiols in BC serum samples significantly changed compared to the healthy control (HC).
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http://dx.doi.org/10.1016/j.aca.2020.01.027DOI Listing
April 2020

2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) induces mitochondrial dysfunction and related liver injury via eliciting miR-34a-5p-mediated mitophagy impairment.

Authors:
Feng Chen Li Feng Yuan-Lin Zheng Jun Lu Shao-Hua Fan Qu Shan Gui-Hong Zheng Yong-Jian Wang Dong-Mei Wu Meng-Qiu Li Qing-Qing Wang Zi-Feng Zhang

Environ Pollut 2020 Mar 6;258:113693. Epub 2019 Dec 6.

School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; College of Health Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China. Electronic address:

2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is associated with various adverse human health effects; however, the knowledge of its toxicity is still very limited. Mitochondrial injury has been observed in liver cells exposed to BDE-47 in vitro. Mitophagy impairment causes the accumulation of dysfunctional mitochondria, contributing to the pathological mechanisms of liver injury. The aim of this study was to investigate whether BDE-47 impairs mitophagy to trigger mitochondrial dysfunction-related liver injury and the underlying mechanisms. This study revealed that BDE-47 elicited mitochondrial dysfunction and related oxidative liver injury by impairing mitophagy. Moreover, our results showed that NAD insufficiency is responsible for BDE-47-mediated mitophagy defect and mitochondrial dysfunction in mouse livers, which was associated with suppression of Sirt3/FoxO3a/PINK1 signaling. Furthermore, our results indicated a potential role of miR-34a-5p in the hepatotoxicity of BDE-47. Mechanistically, BDE-47 dramatically upregulated miR-34a-5p expression in mouse livers. The data from AAV-sponge-mediated miR-34a-5p inhibition suggested that miR-34a-5p diminished NAD level by directly targeting NAMPT expression in BDE-47-treated mouse livers, which was confirmed by luciferase reporter assay. Consequently, miR-34a-5p markedly abated Sirt3/FoxO3a/PINK1 signaling-mediated mitophagy to promote mitochondrial dysfunction in BDE-47-treated mouse livers. The present study provided in vivo evidence to reveal a potential mechanism for BDE-47-induced mitochondrial dysfunction and related liver injury and indicated that miR-34a-5p-mediated mitophagy impairment might be a therapeutic target for BDE-47 toxicity.
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http://dx.doi.org/10.1016/j.envpol.2019.113693DOI Listing
March 2020

Comprehensive RNA-Seq Data Analysis Identifies Key mRNAs and lncRNAs in Atrial Fibrillation.

Authors:
Dong-Mei Wu Zheng-Kun Zhou Shao-Hua Fan Zi-Hui Zheng Xin Wen Xin-Rui Han Shan Wang Yong-Jian Wang Zi-Feng Zhang Qun Shan Meng-Qiu Li Bin Hu Jun Lu Gui-Quan Chen Xiao-Wu Hong Yuan-Lin Zheng

Front Genet 2019 2;10:908. Epub 2019 Oct 2.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, China.

Long non-coding RNAs (lncRNAs) are an emerging class of RNA species that may play a critical regulatory role in gene expression. However, the association between lncRNAs and atrial fibrillation (AF) is still not fully understood. In this study, we used RNA sequencing data to identify and quantify the both protein coding genes (PCGs) and lncRNAs. The high enrichment of these up-regulated genes in biological functions concerning response to virus and inflammatory response suggested that chronic viral infection may lead to activated inflammatory pathways, thereby alter the electrophysiology, structure, and autonomic remodeling of the atria. In contrast, the downregulated GO terms were related to the response to saccharides. To identify key lncRNAs involved in AF, we predicted lncRNAs regulating expression of the adjacent PCGs, and characterized biological function of the dysregulated lncRNAs. We found that two lncRNAs, ETF1P2, and AP001053.11, could interact with protein-coding genes (PCGs), which were implicated in AF. In conclusion, we identified key PCGs and lncRNAs, which may be implicated in AF, which not only improves our understanding of the roles of lncRNAs in AF, but also provides potentially functional lncRNAs for AF researchers.
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http://dx.doi.org/10.3389/fgene.2019.00908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783610PMC
October 2019

LncRNA AB209371 up-regulated Survivin gene by down-regulating miR-203 in ovarian carcinoma.

Authors:
Zi-Hui Zheng Dong-Mei Wu Shao-Hua Fan Xin Wen Xin-Rui Han Shan Wang Yong-Jian Wang Zi-Feng Zhang Qun Shan Meng-Qiu Li Bin Hu Yuan-Lin Zheng Jun Lu

J Ovarian Res 2019 Oct 10;12(1):92. Epub 2019 Oct 10.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science; College of Health Sciences, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116, Jiangsu Province, People's Republic of China.

AB209371 gene has been characterized as an oncogenic lncRNA in liver cancer. However, its involvement in ovarian carcinoma (OC) is unknown. In the present study, we analyzed the roles of AB209371 in OC. We found that AB209371 gene and Survivin gene were up-regulated in OC and positively correlated with OC development. AB209371 over-expression led to up-regulated Survivin in OC cells, while Survivin over-expression failed to affect AB209371. In addition, AB209371 over-expression led to down-regulated miR-203. However, miR-203 over-expression failed to affect AB209371, but down-regulated the expression of Survivin. In addition, over-expressions of AB209371 and Survivin resulted in the increased proliferation rate of OC cells. Over-expression MiR-203 played the opposite role and attenuated the effects of AB209371 over-expression. Therefore, AB209371 may down-regulate miR-203 to up-regulate Survivin, thereby promoting OC cell proliferation. Our study provided novel insights into the pathogenesis of OC.
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http://dx.doi.org/10.1186/s13048-019-0559-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785849PMC
October 2019

gen. nov. (Polyporaceae, Basidiomycota) evidenced by morphological characters and phylogenetic analyses with descriptions of four new species.

Authors:
Xing Ji Dong-Mei Wu Shun Liu Jing Si Bao-Kai Cui

MycoKeys 2019 21;57:61-84. Epub 2019 Aug 21.

Institute of Microbiology, School of Ecology and Nature Conservation, Beijing Forestry University, Beijing 100083, China Beijing Forestry University Beijing China.

A new poroid wood-inhabiting fungal genus, gen. nov., is proposed on the basis of morphological characters and molecular evidence. The genus is characterized by an annual growth habit, effused-reflexed to pileate basidiocarps with pale yellowish brown to yellowish brown, concentrically zonate or sulcate, and velutinate pileal surface, a trimitic hyphal system with clamped generative hyphae, tissues turning to dark in KOH, oblong to broadly ellipsoid, hyaline, smooth, and slightly thick-walled basidiospores. Phylogenetic analysis based on ITS+nLSU sequences indicate that belongs to the core polyporoid clade. The combined ITS+nLSU+mtSSU+EF1-α+RPB2 sequences dataset of representative taxa in the Polyporaceae demonstrate that is grouped with but forms a monophyletic lineage. In addition, four new species of , , , , and are described.
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http://dx.doi.org/10.3897/mycokeys.57.38035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713667PMC
August 2019

Ensemble docking-based virtual screening toward identifying inhibitors against Wee1 kinase.

Authors:
Yaping Li Dong-Mei Wu Ling-Mei Kong Shuqun Zhang Haibo Du Wei Sun Li Zhang Yan Li Zhili Zuo

Future Med Chem 2019 08;11(15):1889-1906

State Key Laboratory of Phytochemistry & Plant Resources in West China, Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China.

kinase plays a key role in the arrest of G2/M checkpoint that prevents mitotic entry in response to DNA damage. This work is to discover potent Wee1 inhibitors which can be considered valuable. Herein, Ensemble docking using multiple crystal structures was considered an effective strategy in the virtual screening. The performance of 17 scoring functions obtained from different docking software was evaluated for molecular docking. Two novel compounds B1 and A2 were identified as Wee1 inhibitors with IC values of 10.23 ± 0.505 and 8.72 ± 0.323 μM, respectively. Further cell viability assay demonstrated that the two active compounds exhibited good anticancer activities. This provides a meaningful starting point for further structure optimization to discover more potent Wee1 inhibitors.
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http://dx.doi.org/10.4155/fmc-2019-0022DOI Listing
August 2019

Simultaneous quantitative analysis of multiple sphingoid bases by stable isotope labeling assisted liquid chromatography-mass spectrometry.

Authors:
Shu-Jian Zheng Jie Zheng Hua-Ming Xiao Dong-Mei Wu Yu-Qi Feng

Anal Chim Acta 2019 Nov 9;1082:106-115. Epub 2019 Jul 9.

Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, 430072, PR China. Electronic address:

Sphingoid bases (SBs) are one of important components of cell membranes, playing important roles in cellular biology. Meanwhile, SBs are associated with various metabolic diseases such as Type 2 Diabetes mellitus (T2DM). Therefore, simultaneous quantitation of multiple SBs in biological samples could provide crucial information for uncovering underlying mechanisms of SBs related functions and diseases. However, existing methods are difficult to achieve simultaneous quantitation for multiple SBs due to the lack of isotope internal standards (ISs) of corresponding SBs. In the current study, we developed a highly sensitive method for the simultaneous detection of 26 SBs in biological samples by stable isotope labeling coupled with ultra-high performance liquid chromatography tandem mass spectrometry (SIL-UHPLC-MS/MS) analysis. In this respect, a pair of isotope labeling reagents, 3-(N, N-dimethylamino)propyl isothiocyanate (DMPI) and d-3-(N, N-dimethylamino)propyl isothiocyanate (d-DMPI), were synthesized and utilized to label SBs in biological samples and SB standards, respectively. The d-DMPI labeled SB standards were used as ISs to calibrate quantitation deviation in MS analysis from the biological matrix. Using the developed method, we successfully quantitated 19 SBs in cells, 20 SBs in mice feces and 18 SBs in human serum samples. Three C17-SBs used as ISs in many reported works were even found in all prepared samples. In summary, the developed SIL-UHPLC-MS/MS analysis was demonstrated to be a promising method for the simultaneous determination of multiple SBs, which could facilitate the investigation of cellular function of SBs and pathogenesis of related diseases.
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http://dx.doi.org/10.1016/j.aca.2019.07.016DOI Listing
November 2019

Six new species and two new records of in China using phylogenetic and morphological analyses.

Authors:
Xi-Hui Du Dong-Mei Wu Guo-Qiang He Wei Wei Nan Xu Ting-Ling Li

Mycologia 2019 Sep-Oct;111(5):857-870. Epub 2019 Aug 15.

College of Life Sciences, Chongqing Normal University , Chongqing , 401331 , China.

In this paper, species of the genus are investigated in China. Based on morphological characteristics and molecular phylogenetic analyses of the nuc rDNA internal transcribed spacer region ITS1-5.8S-ITS2 (ITS) and the combined data set ITS + nuclear large subunit rDNA (28S) + the translation elongation factor 1-α () gene + RNA polymerase II first largest subunit () + RNA polymerase II second largest subunit (), six new phylogenetic species are illustrated and described: , and . Furthermore, two new record species, and , which were only known in Europe, are now reported for the first time from Asia. New species of morels will provide additional information on species diversity and genetic resource candidates for improving the cultivation of this economically important fungus.
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http://dx.doi.org/10.1080/00275514.2019.1640012DOI Listing
March 2020

4-Plex Chemical Labeling Strategy Based on Cinchona Alkaloid-Derived Primary Amines for the Analysis of Chiral Carboxylic Acids by Liquid Chromatography-Mass Spectrometry.

Authors:
Jie Zheng Shu-Jian Zheng Chu-Bo Qi Dong-Mei Wu Yu-Qi Feng

Anal Chem 2019 09 20;91(17):11440-11446. Epub 2019 Aug 20.

Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry , Wuhan University , Wuhan 430072 , People's Republic of China.

Chiral carboxylic acids play important roles in energy metabolism and signal transduction in the human body. These enantiomers usually possess different bioactivities and are also associated with the development of some diseases. Therefore, simultaneous determination of multiple chiral carboxylic acids is vital for study of the pathogenesis of related diseases. However, it is still challenging to simultaneously detect the enantiomers of multiple chiral carboxylic acids in biological samples. Here, we developed a novel 4-plex chemical labeling strategy based on 4 analogues of cinchona alkaloid-derived primary amines (CAPAs) for simultaneous determination of 16 enantiomers of 8 chiral carboxylic acids by liquid chromatography-mass spectrometry (LC-MS). To achieve high-throughput analysis, one CAPA analogue was used to label chiral carboxylic acid standards and served as internal standards (ISs), while the other 3 CAPA analogues were used to label endogenous chiral carboxylic acids in 3 different biological samples. After CAPAs labeling, the 16 chiral carboxylic acid enantiomers could be detected by LC-MS, and their detection sensitivity was greatly enhanced by up to 3 orders of magnitude compared to intact analytes. Further, the developed method for the determination of 16 chiral carboxylic acid enantiomers was validated in human serums and mammalian cells. Finally, the proposed method was applied to the determination of chiral carboxylic acids in the serum samples from type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) patients. We found that 5 chiral carboxylic acid enantiomers in T2DM serum samples and 4 chiral carboxylic acid enantiomers in CRC serum samples exhibited significant change compared to the healthy control (HC).
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http://dx.doi.org/10.1021/acs.analchem.9b02909DOI Listing
September 2019

Sulforaphane administration alleviates diffuse axonal injury (DAI) via regulation signaling pathway of NRF2 and HO-1.

Authors:
Dong-Mei Wu Zi-Hui Zheng Shao-Hua Fan Zi-Feng Zhang Gui-Quan Chen Jun Lu

J Cell Biochem 2020 01 24;121(1):430-442. Epub 2019 Jun 24.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, China.

Background: Nuclear factor erythroid 2-related factor 2 (Nrf2) can alleviate diffuse axonal injury (DAI)-induced apoptosis by regulating expression of heme oxygenase-1 (HO-1), while sulforaphane (SFN) was shown to reduce oxidative stress by increasing the expression of Nrf2. Therefore, we aimed to investigate therapeutic effect of SFN in the treatment of DAI and the ability of SFN to reduce oxidative stress.

Methods: The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to observe the effects of H O and SFN on cell viability. Fluorometric assay, Western blot analysis, and flow cytometry were conducted to validate the protective role of SFN in an animal model of DAI. In addition, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured in DAI rats treated by SFN, while Western blot, immunohistochemistry assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were carried out to verify the effect of SFN in different animal groups.

Results: Cell viability was reduced by H O in a dose-dependent manner, while the treatment by SFN significantly promoted cell growth. Meanwhile the administration of SFN effectively reduced the levels of caspase-3/poly(ADP-ribose) polymerase (PARP) activity increased by the H O treatment, indicating that the protective effect of SFN could be mediated by its ability to suppress caspase-3 activation and PARP cleavage. In addition, the SFN treatment reduced the intracellular reactive oxygen species (ROS) generation induced by H O . Moreover, the MDA levels of SOD/GPx activity in various rat groups showed the protective effects of SFN in DAI rats. It is suspected that the protective effect of SFN was exerted via the activation of the Nrf2/HO-1 signaling pathway. In this study, DAI and DAI + phosphate-buffered saline (PBS) groups also showed the presence of more TUNEL-positive cells compared with the sham-operated group, while the SFN treatment reduced the extent of neuronal apoptosis.

Conclusions: By activating the Nrf2/HO-1 signaling pathway and reducing the activity of caspase-3, SFN reduces the apoptosis of neurons in brain trauma-induced DAI.
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http://dx.doi.org/10.1002/jcb.29203DOI Listing
January 2020

Upregulation of miR-675-5p induced by lncRNA H19 was associated with tumor progression and development by targeting tumor suppressor p53 in non-small cell lung cancer.

Authors:
Zi-Hui Zheng Dong-Mei Wu Shao-Hua Fan Zi-Feng Zhang Gui-Quan Chen Jun Lu

J Cell Biochem 2019 11 20;120(11):18724-18735. Epub 2019 Jun 20.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, P. R. China.

Lung cancer is the main cause of cancer-related death, and the proportion of non-small cell lung cancer (NSCLC) on lung cancer is 85%, while more than 80% lung cancer patients are diagnosed with chronic obstructive pulmonary disease (COPD). In this study, we aimed to explore the potential mechanism of COPD induced NSCLC. Luciferase assay and reverse transcription-polymerase chain reaction (RT-PCR) were conducted to study the regulatory relationship between P53 and microRNA-675 (miR-675). Real-time PCR, Western-blot analysis, and MTT assay were performed to explore the impact of H19 and miR-675 in the signaling pathway involved in COPD induced NSCLC. In NSCLC patients with COPD, H19 and miR-675 levels were strikingly upregulated while P53 level was significantly downregulated. P53 was identified as a target gene of miR-675, and H19 remarkably upregulated miR-675, while H19 siRNA notably inhibited miR-675. In addition, miR-675 and H19 dramatically suppressed the expression of P53 and Bax while inducing the expression of Bcl-2. Finally, H19 and miR-675 induced proliferation of A549 and MRC-5 cells. These finding indicated that COPD (hypoxia)-induced H19 promoted expression of miR-675 associated with NSCLC though target apoptosis-related protein P53, BAX, and Bcl-2.
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http://dx.doi.org/10.1002/jcb.29182DOI Listing
November 2019

FBXW7 suppresses HMGB1-mediated innate immune signaling to attenuate hepatic inflammation and insulin resistance in a mouse model of nonalcoholic fatty liver disease.

Authors:
Cheng Zhang Feng Chen Li Feng Qun Shan Gui-Hong Zheng Yong-Jian Wang Jun Lu Shao-Hua Fan Chun-Hui Sun Dong-Mei Wu Meng-Qiu Li Bin Hu Qing-Qing Wang Zi-Feng Zhang Yuan-Lin Zheng

Mol Med 2019 06 18;25(1):29. Epub 2019 Jun 18.

School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China.

Background: Innate immune dysfunction contributes to the development and progression of nonalcoholic fatty liver disease (NAFLD), however, its pathogenesis is still incompletely understood. Identifying the key innate immune component responsible for the pathogenesis of NAFLD and clarifying the underlying mechanisms may provide therapeutic targets for NAFLD. Recently, F-box- and WD repeat domain-containing 7 (FBXW7) exhibits a regulatory role in hepatic glucose and lipid metabolism. This study aims to investigate whether FBXW7 controls high-mobility group box 1 protein (HMGB1)-mediated innate immune signaling to improve NAFLD and the mechanism underlying this action.

Methods: Mice were fed a high-fat diet (HFD) for 12 or 20 weeks to establish NAFLD model. Hepatic overexpression or knockdown of FBXW7 was induced by tail-vein injection of recombinant adenovirus. Some Ad-FBXW7-injected mice fed a HFD were injected intraperitoneally with recombinant mouse HMGB1 to confirm the protective role of FBXW7 in NAFLD via inhibition of HMGB1.

Results: FBXW7 improves NAFLD and related metabolic parameters without remarkable influence of body weight and food intake. Moreover, FBXW7 markedly ameliorated hepatic inflammation and insulin resistance in the HFD-fed mice. Furthermore, FBXW7 dramatically attenuated the expression and release of HMGB1 in the livers of HFD-fed mice, which is associated with inhibition of protein kinase R (PKR) signaling. Thereby, FBXW7 restrains Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE) signaling in HFD-fed mouse livers. In addition, exogenous HMGB1 treatment abolished FBXW7-mediated inhibition of hepatic inflammation and insulin resistance in HFD-fed mouse livers.

Conclusions: Our results demonstrate a protective role of FBXW7 in NAFLD by abating HMGB1-mediated innate immune signaling to suppress inflammation and consequent insulin resistance, suggesting that FBXW7 is a potential target for therapeutic intervention in NAFLD development.
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http://dx.doi.org/10.1186/s10020-019-0099-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582600PMC
June 2019

Down-regulated lncRNA DLX6-AS1 inhibits tumorigenesis through STAT3 signaling pathway by suppressing CADM1 promoter methylation in liver cancer stem cells.

Authors:
Dong-Mei Wu Zi-Hui Zheng Ying-Bo Zhang Shao-Hua Fan Zi-Feng Zhang Yong-Jian Wang Yuan-Lin Zheng Jun Lu

J Exp Clin Cancer Res 2019 Jun 6;38(1):237. Epub 2019 Jun 6.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China.

Background: Liver cancer stem cells (LCSCs) are a small subset of cells characterized by unlimited self-renewal, cell differentiation, and uncontrollable cellular growth. LCSCs are also resistant to conventional therapies and are thus believed to be held responsible for causing treatment failure of hepatocellular carcinoma (HCC). It has been recently found that long non-coding RNAs (lncRNAs) are important regulators in HCC. This present study aims to explore the underlying mechanism of how lncRNA DLX6-AS1 influences the development of LCSCs and HCC.

Methods: A microarray-based analysis was performed to initially screen differentially expressed lncRNAs associated with HCC. We then analyzed the lncRNA DLX6-AS1 levels as well as CADM1 promoter methylation. The mRNA and protein expression of CADM1, STAT3, CD133, CD13, OCT-4, SOX2, and Nanog were then detected. We quantified our results by evaluating the spheroid formation, proliferation, and tumor formation abilities, as well as the proportion of tumor stem cells, and the recruitment of DNA methyltransferase (DNMT) in LCSCs when lncRNA DLX6-AS1 was either overexpressed or silenced.

Results: LncRNA DLX6-AS1 was upregulated in HCC. The silencing of lncRNA DLX6-AS1 was shown to reduce and inhibit spheroid formation, colony formation, proliferation, and tumor formation abilities, as well as attenuate CD133, CD13, OCT-4, SOX2, and Nanog expression in LCSCs. Furthermore, downregulation of lncRNA DLX6-AS1 contributed to a reduction in CADM1 promoter methylation via suppression of DNMT1, DNMT3a, and DNMT3b in LCSCs and inactivating the STAT3 signaling pathway.

Conclusion: This study demonstrated that down-regulated lncRNA DLX6-AS1 may inhibit the stem cell properties of LCSCs through upregulation of CADM1 by suppressing the methylation of the CADM1 promoter and inactivation of the STAT3 signaling pathway.
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http://dx.doi.org/10.1186/s13046-019-1239-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554918PMC
June 2019

Comparison of bacterial community structure and potential functions in hypoxic and non-hypoxic zones of the Changjiang Estuary.

Authors:
Dong-Mei Wu Qiu-Ping Dai Xue-Zhu Liu Ying-Ping Fan Jian-Xin Wang

PLoS One 2019 6;14(6):e0217431. Epub 2019 Jun 6.

Marine Microorganism Ecological & Application Lab, Zhejiang Ocean University, Zhejiang, China.

Bacterioplankton play a key role in the global cycling of elements. To characterize the effects of hypoxia on bacterioplankton, bacterial community structure and function were investigated in the Changjiang Estuary. Water samples were collected from three layers (surface, middle, and bottom) at ten sampling sites in the Changjiang Estuary hypoxic and non-hypoxic zones. The community structure was analyzed using high-throughput sequencing of 16S rDNA genes, and the predictive metagenomic approach was used to investigate the functions of the bacterial community. Co-occurrence networks are constructed to investigate the relationship between different bacterioplankton. The results showed that community composition in hypoxic and non-hypoxic zones were markedly different. The diversity and richness of bacterial communities in the bottom layer (hypoxic zone) were remarkably higher than that of the surface layer (non-hypoxic). In the non-hypoxic zone, it was found that Proteobacteria, Bacteroidetes, and Flavobacteriia were the dominant groups while Alphaproteobacteria, SAR406 and Deltaproteobacteria were the dominant groups in the hypoxic zone. From the RDA analysis, it was shown that dissolved oxygen (DO) explained most of the bacterial community variation in the redundancy analysis targeting only hypoxia zones, whereas nutrients and salinity explained most of the variation across all samples in the Changjiang Estuary. To understand the genes involved in nitrogen metabolism, an analysis of the oxidation state of nitrogen was performed. The results showed that the bacterial community in the surface layer (non-hypoxic) had more genes involved in dissimilatory nitrate reduction, assimilatory nitrate reduction, denitrification, and anammox, while that in the middle and bottom layers (hypoxic zone) had more abundant genes associated with nitrogen fixation and nitrification. Co-occurrence networks revealed that microbial assemblages in the middle and bottom layers shared more niche spaces than in the surface layer (non-hypoxic zone). The environmental heterogeneity in the hypoxic and non-hypoxic zones might be important environmental factors that determine the bacterial composition in these two zones.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217431PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553723PMC
February 2020

Stochastic sensitivity analysis of noise-induced transitions in a predator-prey model with environmental toxins.

Authors:
Dong Mei Wu Hao Wang San Ling Yuan

Math Biosci Eng 2019 03;16(4):2141-2153

College of Science, University of Shanghai for Science and Technology, Shanghai, 200093, China.

Huang et al. [1] recently developed a toxin-dependent predator-prey model and analyzed its global dynamics. Their results showed that environmental toxins may influence both predators and prey and induce bistable situation, and intermediate toxin concentrations may affect predators disproportionately through biomagnification. Environmental noises can change the dynamical behaviors of the toxin-based predator-prey model. In this paper, by formulating a stochastically forced predator-prey model with environmental toxins, we study the dynamical phenomenon of noise-induced transitions from coexistence to prey-only extirpation in the bistable zone. Numerical simulations based on the technique of stochastic sensitivity functions are provided for constructing the confidence ellipse and estimating the threshold value of the noise intensity of state switching. Meanwhile, we construct the confidence band and study the configurational arrangement of the stochastic cycle.
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http://dx.doi.org/10.3934/mbe.2019104DOI Listing
March 2019

Association between plasma macrophage migration inhibitor factor and deep vein thrombosis in patients with spinal cord injuries.

Authors:
Dong-Mei Wu Zi-Hui Zheng Shan Wang Xin Wen Xin-Rui Han Yong-Jian Wang Min Shen Shao-Hua Fan Zi-Feng Zhang Qun Shan Meng-Qiu Li Bin Hu Yuan-Lin Zheng Gui-Quan Chen Jun Lu

Aging (Albany NY) 2019 04;11(8):2447-2456

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, P.R. China.

The patients with spinal cord injury (SCI) suffered significantly higher risk of deep vein thrombosis (DVT) than normal population. The aim was to assess the clinical significance of macrophage migration inhibitory factor (MIF) as the risk factor for DVT in acute SCI patients. 207 Chinese patients were enrolled in this study, including thirty-nine (39) patients (18.8 %; 95 %CI: 13.5 %-24.2 %) diagnosed as DVT at the follow-up of 1 month. Nine (9) of the 39 patients (23.1%) were suspected of thrombosis before the screening. The MIF levels in plasma of DVT patients were significantly higher than DVT-free patients. The risks of DVT would be increased by 11 % (OR : 1.11; 95% CI, 1.06-1.17, P<0.001) and 8 % (OR : 1.08; 1.03-1.14, P=0.001), for each additional 1 ng/ml of MIF level. Furthermore, after MIF was combined with established risk factors, area under the receiver operating characteristic curve (standard error) was increased from 0.82(0.035) to 0.85(0.030). The results showed the potential association between the high MIF levels in plasma and elevated DVT risk in SCI patients, which may assist on early intervention.
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http://dx.doi.org/10.18632/aging.101935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520010PMC
April 2019

Impact of serum omentin-1 levels on functional prognosis in nondiabetic patients with ischemic stroke.

Authors:
Dong-Mei Wu Shan Wang Xin Wen Xin-Rui Han Yong-Jian Wang Min Shen Shao-Hua Fan Zi-Feng Zhang Qun Shan Meng-Qiu Li Bin Hu Jun Lu Gui-Quan Chen Yuan-Lin Zheng

Am J Transl Res 2019 15;11(3):1854-1863. Epub 2019 Mar 15.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University Xuzhou 221116, P. R. China.

Objective: Omentin-1, an adipokine released from visceral fat tissue, is associated with diabetes and stroke. The purpose of this study was to assess the impact of serum omentin-1 levels on functional prognosis in nondiabetic patients with ischemic stroke.

Methods: From March 2016 to December 2017, consecutive patients with first-ever ischemic stroke admitted to our hospital, China, were recorded. Functional impairment was evaluated at 3-month after admission using the modified Rankin scale (mRS). Uni-and multivariate analyses with Cox proportional hazard regression was used for assessing the relationship between serum level of omentin-1 and functional outcome.

Results: We recorded 209 stroke patients, 52 of them (24.9%) experienced as poor functional outcome. The obtained omentin-1 level in patients with poor outcome was lower than in those patients with good outcome [100.8 (80.9-131.6) ng/ml vs. 137.6 (IQR, 106.1-171.5) ng/ml; Z=4.692; P<0.001). Multivariate analysis models were used to assess stroke outcome according to omentin-1 quartiles (the highest quartile [Q4] as the reference), the 1 and 2 quartile of omentin-1 were compared against the Q4, and the risks were increased by 505% (HR=6.05; 95% CI: 2.13-12.15; P=0.007) and 215% (31.5; 1.21-7.98; P=0.03), respectively. The inclusion of omentin-1 in the routine prediction model for the prediction of poor functional outcome, enhanced the NRI (P=0.006) and IDI (P=0.001) values, confirming the effective reclassification and discrimination. Kaplan-Meier analysis suggested that the patients with low serum omentin-1 levels had a higher risk of death than those patients with high levels of omentin-1 (log-rank test P=0.033).

Conclusion: In this cohort of nondiabetic patients with ischemic stroke, a reduced baseline level of serum omentin-1 was related with an increased risk for poor functional outcome or death, independent of baseline variables.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456553PMC
March 2019

Bone Marrow Mesenchymal Stem Cell-Derived Exosomal MicroRNA-126-3p Inhibits Pancreatic Cancer Development by Targeting ADAM9.

Authors:
Dong-Mei Wu Xin Wen Xin-Rui Han Shan Wang Yong-Jian Wang Min Shen Shao-Hua Fan Zi-Feng Zhang Qun Shan Meng-Qiu Li Bin Hu Jun Lu Gui-Quan Chen Yuan-Lin Zheng

Mol Ther Nucleic Acids 2019 Jun 1;16:229-245. Epub 2019 Mar 1.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou 221116, China; College of Health Sciences, Jiangsu Normal University, Xuzhou 221116, Jiangsu, China. Electronic address:

Pancreatic cancer is a lethal malignancy with relatively few effective therapies. Recent investigations have highlighted the role of microRNAs (miRNAs) as crucial regulators in various tumor processes including tumor progression. Hence the current study aimed to investigate the role of bone marrow mesenchymal stem cell (BMSC)-derived exosomal microRNA-126-3p (miR-126-3p) in pancreatic cancer. Initially, miRNA candidates and related genes associated with pancreatic cancer were screened. PANC-1 cells were transfected with miR-126-3p or silenced a disintegrin and a metalloproteinase-9 (ADAM9) to examine their regulatory roles in pancreatic cancer cells. Additionally, exosomes derived from BMSCs were isolated and co-cultured with pancreatic cancer cells to elucidate the effects of exosomes in pancreatic cancer. Furthermore, the effects of overexpressed miR-126-3p derived from BMSCs exosomes on proliferation, migration, invasion, apoptosis, tumor growth, and metastasis of pancreatic cancer cells were analyzed in connection with lentiviral packaged miR-126-3p in vivo. Restored miR-126-3p was observed to suppress pancreatic cancer through downregulating ADAM9. Notably, overexpressed miR-126-3p derived from BMSCs exosomes inhibited the proliferation, invasion, and metastasis of pancreatic cancer cells, and promoted their apoptosis both in vitro and in vivo. Taken together, the key findings of the study indicated that overexpressed miR-126-3p derived from BMSCs exosomes inhibited the development of pancreatic cancer through the downregulation of ADAM9, highlighting the potential of miR-126-3p as a novel biomarker for pancreatic cancer treatment.
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http://dx.doi.org/10.1016/j.omtn.2019.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439275PMC
June 2019

Roles of β-catenin, TCF-4, and survivin in nasopharyngeal carcinoma: correlation with clinicopathological features and prognostic significance.

Authors:
Pei-Ying Jin Zi-Hui Zheng Hong-Jie Lu Jing Yan Gui-Hong Zheng Yuan-Lin Zheng Dong-Mei Wu Jun Lu

Cancer Cell Int 2019 28;19:48. Epub 2019 Feb 28.

1Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, No. 101, Shanghai Road, Tongshan District, Xuzhou, 221116 Jiangsu People's Republic of China.

Background: Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck region with poorly understood progression and prognosis. The present study aims at exploring whether the expression of β-catenin, TCF-4, and survivin affects clinicopathological features and prognostic significance in NPC.

Methods: We enrolled 164 patients with NPC and 70 patients with chronic nasopharyngitis (CNP) in this study. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) were conducted to evaluate the expression of β-catenin, TCF-4, and survivin. Spearman's rank correlation analysis and Pearson correlation analysis were used to measure the correlation of β-catenin, TCF-4, and survivin. Risk factors for prognosis and survival conditions of NPC patients were analyzed by Cox proportional hazards model and Kaplan-Meier curves.

Results: The results obtained revealed that mRNA and protein expression of β-catenin, TCF-4, and survivin was higher in NPC tissues than in CNP tissues. Positive correlations amongst β-catenin, TCF-4, and survivin were identified by Spearman's rank correlation analysis and Pearson correlation analysis. There was a significant correlation in expression of β-catenin, TCF-4, and survivin with EBV DNA, EBV-VCA-IgA, EBV-EA-IgA, T stage, N stage, and clinicopathological stages. Lower overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), and disease-free survival (DFS) rates were detected in NPC patients with positive expression of β-catenin, TCF-4, and survivin, in contrast to those with negative expression. Cox proportional hazards model demonstrated that β-catenin, TCF-4, and survivin protein positive expression were independent risk factors for OS and DFS of NPC prognosis; there was an evident correlation between clinicopathological stages, TCF-4, and EBV-EA-IgA and OS, DMFS, LRFS, and DFS of NPC.

Conclusions: The aforementioned results indicate that β-catenin, TCF-4, and survivin proteins are highly expressed in NPC, which can be used as factors to predict the malignancy of NPC. In addition, positive expression of β-catenin, TCF-4, and survivin are potential risk factors that lead to an unfavorable prognosis of OS and DFS in NPC patients.
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http://dx.doi.org/10.1186/s12935-019-0764-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396483PMC
February 2019

Purple Sweet Potato Color Attenuates Kidney Damage by Blocking VEGFR2/ROS/NLRP3 Signaling in High-Fat Diet-Treated Mice.

Authors:
Gui-Hong Zheng Qun Shan Jing-Jing Mu Yong-Jian Wang Zi-Feng Zhang Shao-Hua Fan Bin Hu Meng-Qiu Li Jun Xie Ping Chen Dong-Mei Wu Jun Lu Yuan-Lin Zheng

Oxid Med Cell Longev 2019 22;2019:5189819. Epub 2019 Jan 22.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, 221116 Jiangsu Province, China.

Our preliminary data showed that VEGFR2 upregulation promoted renal ROS overproduction in high-fat diet- (HFD-) treated mice. Given that ROS-induced NLRP3 activation plays a central role in the pathogenesis of type 2 diabetic kidney injury, we evaluate whether VEGFR2 upregulation induces type 2 diabetic kidney injury via ROS-mediated NLRP3 activation and further explore the underlying mechanism. Our results showed that VEGFR2 knockdown decreased ROS overproduction, blocked NLRP3-dependent inflammation, and alleviated kidney damage in HFD-treated mice. Treatment with -lipoic acid, a scavenger of ROS, lowered ROS overproduction and alleviated NLRP3-triggered kidney injury of HFD-treated mice. Collectively, the VEGFR2/ROS/NLRP3 signal is a critical therapeutic strategy for the kidney injury of HFD-treated mice. Purple sweet potato color (PSPC), a natural anthocyanin, can exert renal protection by inhibiting ROS in HFD-treated mice. Here, we provide a novel mechanism of PSPC against renal damage in HFD-treated mice by downregulating VEGFR2 expression.
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http://dx.doi.org/10.1155/2019/5189819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360596PMC
March 2019

The role of HOTAIR-induced downregulation of microRNA-126 and interleukin-13 in the development of bronchial hyperresponsiveness in neonates.

Authors:
Dong-Mei Wu Zi-Hui Zheng Shan Wang Xin Wen Xin-Rui Han Yong-Jian Wang Min Shen Shao-Hua Fan Zi-Feng Zhang Qun Shan Meng-Qiu Li Bin Hu Yuan-Lin Zheng Gui-Quan Chen Jun Lu

J Cell Physiol 2019 Feb 21. Epub 2019 Feb 21.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu, School of Life Science, College of Health Sciences, Jiangsu Normal University, Xuzhou, China.

Long noncoding RNAs, including HOTAIR, are involved in the pathogenesis of a wide range of diseases. This study aimed to explore the mechanism underlying the involvement of HOTAIR in neonatal bronchial hyperresponsiveness (BHR). A total of 105 newborns were recruited in this study to collect their peripheral blood mononuclear cell and serum samples, which were then divided into different genotype groups based on the genotypes of rs4759314, rs874945, and rs7958904. The real-time polymerase chain reaction, western blot analysis, computational analyses, and luciferase assays were performed to establish the regulatory relationships between the HOTAIR, microRNA-126 (miR-126), and interleukin-13 (IL-13). The level of HOTAIR, miR-126, and IL-13 among rs4759314 AA, AG, and GG groups, as well as among rs874945 GG, AG, and AA groups was similar. However, the level of HOTAIR was increased in the rs7958904 GG group, accompanied by a decreased level of miR-126 and IL-13. In addition, the level of airway responsiveness was comparable among rs4759314 AA, AG, and GG groups, as well as among rs874945 GG, AG, and AA groups. However, the airway responsiveness in the groups rs7958904 CG and CC was much stronger than that of the GG group. We also demonstrated that, by directly binding to miR-126, HOTAIR reduced the expression of miR-126, which in turn decreased the expression of IL-13. In summary, we demonstrated the role of HOTAIR-induced downregulation of miR-126 and IL-13 in the development of BHR in neonates.
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http://dx.doi.org/10.1002/jcp.28309DOI Listing
February 2019

Delivery of Doxorubicin from Hyaluronic Acid-Modified Glutathione-Responsive Ferrocene Micelles for Combination Cancer Therapy.

Authors:
Hong-Lin Mao Feng Qian Shun Li Jia-Wei Shen Cheng-Kun Ye Lei Hua Long-Zhen Zhang Dong-Mei Wu Jun Lu Ru-Tong Yu Hong-Mei Liu

Mol Pharm 2019 03 25;16(3):987-994. Epub 2019 Jan 25.

Institute of Nervous System Diseases , Xuzhou Medical University , Xuzhou 221002 , P.R. China.

A combination of different chemotherapy approaches can obtain the best response for many cancers. However, the greatest challenge is the development of a nanoparticle formulation that can encapsulate different chemotherapeutic agents to achieve the proper synergetic chemotherapy for the tumor. Here, amphiphilic ferrocenium-tetradecyl (Fe-C) was constructed to form cationic micelles in an aqueous solution via self-assembly. Then, it was coated by hyaluronic acid (HA) through electrostatic interactions to generate HA-Fe-C micelles. The HA-Fe-C micelles were used to deliver doxorubicin (DOX), and it showed that the DOX could be released rapidly under a high-GSH tumor environment. The HA-Fe-C/DOX micelles were able to accumulate efficiently in tumor and showed significant anticancer effect both in vitro and in vivo. These results suggest that HA-Fe-C/DOX micelles are a useful drug delivery system that enhances synergic antitumor treatment effects.
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00862DOI Listing
March 2019

High-throughput screening of novel pyruvate dehydrogenase kinases inhibitors and biological evaluation of their in vitro and in vivo antiproliferative activity.

Authors:
Dong-Mei Wu Yong-Jian Wang Shao-Hua Fan Zi-Feng Zhang Qun Shan Jun Lu Gui-Quan Chen Yuan-Lin Zheng

Eur J Med Chem 2019 Feb 24;164:252-262. Epub 2018 Dec 24.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, PR China; College of Health Sciences, Jiangsu Normal University, Xuzhou, 221116, PR China. Electronic address:

Overexpression of pyruvate dehydrogenase kinases (PDKs) has been widely noticed in a variety of human solid tumors, which could be regarded as an attractive therapeutic target for cancer therapy. In this paper, we present an enzymatic screening assay and multiple biological evaluations for the identification of potential PDKs, especially PDK1 inhibitors. We identified 9 potential PDKs inhibitors from the screening of an in-house small molecule library, all of the identified inhibitors reduced pyruvate dehydrogenase (PDH) complex phosphorylation. Among which, 4, 5, and 9 displayed the most potent PDKs inhibitory activities, with EC values of 0.34, 1.4, and 1.6 μM in an enzymatic assay, respectively. A kinase inhibition assay suggested that 4, 5, and 9 were pan-isoform PDK inhibitors, but more sensitive to PDK1. Meanwhile, the three compounds inhibited HSP90, with IC values of 0.78, 3.58, and 2.70 μM, respectively. The cell viability assay indicated that 4 inhibited all of the tested cancer cells proliferation, with a GC value of 2.3 μM against NCIH1975 cell, but has little effect on human normal lung cell BEAS-2B cell. In the NCIH1975 xenograft models, 4 displayed strong antitumor activities at a dose of 10 and 20 mg/kg, but with no negative effect on the mice weight. In addition, 4 decreased the ECAR and lactate formation, increased OCR and ROS level in NCIH1975 cancer cell, which could be used as a promising modulator to reprogram the glucose metabolic pathways in NCIH1975 cancer cells.
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http://dx.doi.org/10.1016/j.ejmech.2018.12.051DOI Listing
February 2019

Long noncoding RNA nuclear enriched abundant transcript 1 impacts cell proliferation, invasion, and migration of glioma through regulating miR-139-5p/ CDK6.

Authors:
Dong-Mei Wu Shan Wang Xin Wen Xin-Rui Han Yong-Jian Wang Shao-Hua Fan Zi-Feng Zhang Qun Shan Jun Lu Yuan-Lin Zheng

J Cell Physiol 2019 05 4;234(5):5972-5987. Epub 2018 Dec 4.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, China.

Aims: We aimed to explore the impact of long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) on cell proliferation, invasion, and migration of glioma.

Methods: Differentially expressed genes were screened out from Gene Expression Omnibus data set based on the microarray analysis. The expression levels of lncRNA NEAT1, miR-139-5p, and CDK6 in glioma cells and tissues were examined by quantitative reverse transcription polymerase chain reaction, and the protein level of CDK6 in glioma cells was determined by western blot and immunohistochemistry. Glioma cell viability, cell cycle, and apoptosis were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) and flow cytometry, respectively, whereas cell invasion and migration were analyzed by transwell assay. The target relationships among NEAT1, miR-139-5p, and CDK6 were confirmed by dual-luciferase reporter gene assay. The effects of lncRNA NEAT1 on tumor growth were further testified through glioma xenografts in nude mice.

Results: LncRNA NEAT1 and CDK6 were highly expressed in glioma tissues and cells, whereas miR-139-5p was lowly expressed. There were target relationships and correlations on expressions between miR-139-5p and NEAT1/ CDK6. NEAT1 and CDK6 could promote cell proliferation and metastasis of glioma cells and impeded cell apoptosis, whereas miR-139-5p exerted suppressive effects on the biological functions of glioma cells. NEAT1 regulated CDK6 to affect glioma growth through sponging miR-139-5p.

Conclusions: LncRNA NEAT1 promotes cell proliferation, invasion, and migration of glioma through regulating miR-139-5p/CDK6 pathway.
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http://dx.doi.org/10.1002/jcp.27093DOI Listing
May 2019

Inhibition of microRNA-200a Upregulates the Expression of Striatal Dopamine Receptor D2 to Repress Apoptosis of Striatum via the cAMP/PKA Signaling Pathway in Rats with Parkinson's Disease.

Authors:
Dong-Mei Wu Shan Wang Xin Wen Xin-Rui Han Yong-Jian Wang Min Shen Shao-Hua Fan Juan Zhuang Zi-Feng Zhang Qun Shan Meng-Qiu Li Bin Hu Chun-Hui Sun Jun Lu Yuan-Lin Zheng

Cell Physiol Biochem 2018 29;51(4):1600-1615. Epub 2018 Nov 29.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, China.

Background/aims: Parkinson's disease (PD) is a neurodegenerative movement disease with a high annual incidence. Accumulating evidence demonstrates that microRNAs play important roles in the pathogenesis of multiple neurological disorders, including PD. This study aims to investigate how microRNA-200a (miR-200a) regulates striatal dopamine receptor D2 (DRD2) to affect apoptosis of striatum in rats with PD and to explore the associated mechanism.

Methods: After successfully establishing a PD model by 6-hydroxydopamine injections, PD rats were mainly treated with miR-200a mimics, inhibitors, Forskolin or a combination of miR-200a inhibitors and Forskolin. High-performance liquid chromatography-electrochemical detection (HPLC-ECD) was employed to detect the levels of dopamine, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and chemistry colorimetric methods were applied to detect the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). A TUNEL assay and immunocytochemical staining were performed to observe apoptosis and tyrosine hydroxylase (TH)-positive cells in the striatum. The expression of miR-200a, DRD2, Bad, Bax, Bcl-2, cAMP and PKA was determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assays.

Results: In the cellular experiments, after transfection with the inhibitor of miR-200a, decreased levels of Bax, GSH-Px, SOD, dopamine, DOPAC and HVA but increased levels of MDA and Bcl-2 were found along with a reduced apoptosis rate and increased TH-positive cell number. In addition, downregulating miR-200a resulted in lower expression of AKT, cAMP and PKA but higher expression of DRD2 and CREB, indicating that the downregulation of miR-200a increases DRD2 expression, which blocks the cAMP/PKA signaling pathway.

Conclusion: This study provides evidence that the inhibition of miR-200a can repress apoptosis in the striatum via inhibition of the cAMP/PKA signaling pathway by upregulating DRD2 expression in PD rats.
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http://dx.doi.org/10.1159/000495649DOI Listing
January 2019

Micro-RNA-143 inhibits proliferation and promotes apoptosis of thymocytes by targeting CXCL13 in a myasthenia gravis mouse model.

Authors:
Dong-Mei Wu Xin Wen Xin-Rui Han Shan Wang Yong-Jian Wang Min Shen Shao-Hua Fan Juan Zhuang Zi-Feng Zhang Qun Shan Meng-Qiu Li Bin Hu Chun-Hui Sun Jun Lu Yuan-Lin Zheng

Am J Physiol Cell Physiol 2019 01 7;316(1):C70-C80. Epub 2018 Nov 7.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University , Xuzhou , People's Republic of China.

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder, affecting the quality of life of millions of people worldwide. The present study aims to determine the relationship between micro-RNA-143 (miR-143) and C-X-C motif chemokine 13 (CXCL13) and whether it influences the pathogenesis of myasthenia gravis (MG). Thymus specimens were resected from patients with thymic hyperplasia combined with MG and then infused into normal mouse cavities to establish MG mouse models. Immunohistochemistry, reverse transcription-quantitative PCR, in situ hybridization detection, and Western blot analysis were employed to identify the expression of miR-143 and CXCL13 in MG and normal mice. The obtained thymocytes were cultured in vitro and transfected with a series of miR-143 mimic, miR-143 inhibitor, overexpression of CXCL13, or siRNA against CXCL13. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and flow cytometry assays were employed to assess cell viability, cycle entry, and apoptosis of the thymocytes. Dual-luciferase reporter assay provided verification, confirming that CXCL13 was the target gene of miR-143. Low miR-143 expression in the thymus tissues of the MG mice was detected, which presented with a reciprocal relationship with the expression rate of CLCX13. Observations in relation to the interactions between miR-143 mimic or siRNA-CXCL13 exposure showed reduced cell viability, with a greater number of cells arrested at the G0/G1 phase and a greater rate of induced apoptosis. Furthermore, overexpression of CXCL13 rescued miR-143 mimic-induced apoptosis. The findings have identified the potential role of miR-143 as a MG development mediator by targeting CXCL13. The key results obtained provide a promising experimental basis for targeted intervention treatment with miR-143.
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http://dx.doi.org/10.1152/ajpcell.00090.2018DOI Listing
January 2019

Suppression of microRNA-342-3p increases glutamate transporters and prevents dopaminergic neuron loss through activating the Wnt signaling pathway via p21-activated kinase 1 in mice with Parkinson's disease.

Authors:
Dong-Mei Wu Shan Wang Xin Wen Xin-Rui Han Yong-Jian Wang Min Shen Shao-Hua Fan Juan Zhuang Zi-Feng Zhang Qun Shan Meng-Qiu Li Bin Hu Chun-Hui Sun Jun Lu Gui-Quan Chen Yuan-Lin Zheng

J Cell Physiol 2019 06 26;234(6):9033-9044. Epub 2018 Oct 26.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, China.

Development of effective therapeutic drugs for Parkinson's disease (PD) is of great importance. Aberrant microRNA (miRNA) expression has been identified in postmortem human PD brain samples, in vitro and in vivo PD models. However, the role of miR-342-3p in PD has been understudied. The study explores the effects of miR-342-3p on expression of glutamate (Glu) transporter, and dopaminergic neuron apoptosis and proliferation by targeting p21-activated kinase 1 (PAK1) through the Wnt signaling pathway in PD mice. After establishment of PD mouse models, gain- or loss-of-function assay was performed to explore the functional role of miR-342-3p in PD. Number of apoptotic neurons and Glu concentration was then determined. Subsequently, PC12 cells were treated with miR-342-3p mimic, miR-342-3p inhibitor, dickkopf-1 (DKK1), and miR-342-3p inhibitor + DKK1. The expression of miR-342-3p, PAK1, the Wnt signaling pathway-related and apoptosis-related genes, Glutamate transporter subtype 1 (GLT-1), l-glutamate/ l-aspartate transporter (GLAST), tyrosine hydroxylase (TH) was measured. Also, cell viability and apoptosis were evaluated. PD mice exhibited increased miR-342-3p, while decreased expression of PAK1, GLT-1, GLAST, TH, and the Wnt signaling pathway-related and antiapoptosis genes. miR-342-3p downregulation could promote expression of PAK1, the Wnt signaling pathway-related and antiapoptosis genes. GLT-1, GLAST, and TH as well as cell viability, but reduce cell apoptosis rate. The results indicated that suppression of miR-342-3p improves expression of Glu transporter and promotes dopaminergic neuron proliferation while suppressing apoptosis through the Wnt signaling pathway by targeting PAK1 in mice with PD.
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http://dx.doi.org/10.1002/jcp.27577DOI Listing
June 2019

Cognitive impairment correlates with serum carbonyl compound profiles in subclinical carotid atherosclerosis.

Authors:
Dong-Mei Wu Jun-Jian Zhang Ning Guo Shu-Jian Zheng Quan-Fei Zhu Yu-Qi Feng Si-Si Peng Yan-Hong Wu Ming-Hui Tuo

Neuroreport 2018 12;29(18):1550-1557

Department of Neurology, Zhongnan Hospital of Wuhan University.

Current evidence indicates that carotid atherosclerosis is an independent risk factor for cognitive impairment. Serum metabolomic analysis holds significant promise for uncovering the relationship between carotid atherosclerosis and cognitive impairment. In this study, we aimed to evaluate the profiling of serum carbonyl compounds in subclinical carotid atherosclerosis (SCA) patients and to explore the relationship between serum carbonyl compounds and cognitive performance. We enrolled 51 SCA patients and 45 healthy control individuals using carotid ultrasound assessment. All the participants were subjected to a neuropsychological assessment and their fasting serum samples were collected for untargeted stable isotope-labeling strategy combined with liquid chromatography-double precursor ion scan-mass spectrometry analysis. Compared with the control, the SCA group showed lower scores in global cognition, immediate memory, verbal fluency, executive function, and visual attention. For the isotope-labeling strategy combined with liquid chromatography-double precursor ion scan-mass spectrometry analysis, 149 potential carbonyl candidates were discovered in the pooled serum. In the SCA serum, 41 carbonyl compounds showed significantly increased levels and 14 carbonyl compounds showed significantly decreased levels. In addition, six carbonyl compounds involved in the oxidation of polyunsaturated fatty acids and vitamin E were correlated with cognitive performance. A negative correlation was observed between cognitive performance and the levels of octanal, nonanal, α-tocopherolquinone, and heptanal, respectively. A positive correlation was observed between cognitive performance and the levels of acetophenone and 1-(3-aminopropyl)-4-aminobutanal, respectively. In summary, the SCA individuals have poor cognitive performance, which may be reflected by aberrant serum carbonyl compound profiles.
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http://dx.doi.org/10.1097/WNR.0000000000001147DOI Listing
December 2018

MCL1 gene silencing promotes senescence and apoptosis of glioma cells via inhibition of the PI3K/Akt signaling pathway.

Authors:
Dong-Mei Wu Xiao-Wu Hong Xin Wen Xin-Rui Han Shan Wang Yong-Jian Wang Min Shen Shao-Hua Fan Juan Zhuang Zi-Feng Zhang Qun Shan Meng-Qiu Li Bin Hu Chun-Hui Sun Jun Lu Yuan-Lin Zheng

IUBMB Life 2019 01 8;71(1):81-92. Epub 2018 Oct 8.

Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, 221116, China.

Glioma is known to be the most prevalent primary brain tumor. In recent years, there has been evidence indicating myeloid cell leukemia-1 (MCL1) plays a role in brain glioblastoma. Therefore, the present study was conducted with aims of exploring the ability of MCL1 silencing to influence glioma cell senescence and apoptosis through the mediation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Glioma and tumor-adjacent tissues were collected in order to detect the presence of higher levels of MCL1 protein expression. Next, the mRNA and protein expression of MCL1, PI3K, Akt, B cell lymphoma 2 (Bcl2), Bcl2-associated X (Bax), B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1), and phosphatase and tensin homolog (PTEN) were determined. Cell counting kit-8 assay was applied to detect cell proliferation, β-galactosidase staining for cell senescence, and flow cytometry for cell cycle entry and apoptosis. Initially, the results revealed higher positive expression rate of MCL1 protein, increased mRNA and protein expression of MCL1, PI3K, Akt, Bmi-1, and Bcl-2 and decreased that of Bax and PTEN in human glioma tissues. The silencing of MCL1 resulted in a decrease in mRNA and protein expression of PI3K, Akt, Bmi-1, and Bcl-2 and an increase in Bax and PTEN expressions in glioma cells. Moreover, silencing of MCL1 also inhibited cell proliferation and cell cycle entry in glioma cells, and promoted glioma cell senescence and apoptosis. In conclusion, the aforementioned results collectively suggested that the silencing of MCL1 promotes senescence and apoptosis in glioma cells through inhibiting the PI3K/Akt signaling pathway. Thus, decreasing the expression of MCL1 might have therapeutic functions in glioma. © 2018 IUBMB Life, 71(1):81-92, 2019.
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http://dx.doi.org/10.1002/iub.1944DOI Listing
January 2019