Publications by authors named "Huimin Jiang"

54 Publications

Upregulation of FTX expression is associated with a poor prognosis and contributes to the progression of thyroid cancer.

Oncol Lett 2021 Sep 18;22(3):672. Epub 2021 Jul 18.

Department of Hematology, Anhui No. 2 Provincial People's Hospital, Hefei, Anhui 230041, P.R. China.

The dysregulated expression of long non-coding RNA FTX transcript X inactive specific transcript regulator (FTX) has been reported to be involved in the tumorigenesis of multiple cancer types. However, to the best our knowledge, its function and clinical value in thyroid cancer remain unclear. The present study aimed to determine the potential role of FTX in the development and progression of thyroid cancer. Reverse transcription-quantitative PCR analysis revealed that the expression levels of FTX were upregulated in thyroid cancer tissues and cell lines compared with those in normal tissues and cell lines, respectively. Survival analysis demonstrated that patients with upregulated FTX expression had a lower survival rate. Functional experiments revealed that the knockdown of FTX inhibited proliferation, cell cycle progression, migration and invasion, and induced apoptosis in thyroid cancer cells, while FTX overexpression accelerated proliferation, migration and invasion, and alleviated apoptosis in thyroid cancer cells. In addition, FTX knockdown significantly inhibited tumor growth . Furthermore, in thyroid cancer cells, FTX was identified to positively regulate the expression levels of TGF-β1, which is known to play an important regulatory role in tumor metastasis. In conclusion, the findings of the present study suggested that FTX may accelerate thyroid cancer progression via regulation of cellular activities, including cell proliferation, migration, invasion and apoptosis. Thus, FTX may represent a potential biomarker for the diagnosis, treatment and prognosis of thyroid cancer.
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http://dx.doi.org/10.3892/ol.2021.12933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323005PMC
September 2021

Fructose-1,6-Bisphosphate Aldolase B Depletion Promotes Hepatocellular Carcinogenesis Through Activating Insulin Receptor Signaling and Lipogenesis.

Hepatology 2021 Jul 22. Epub 2021 Jul 22.

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health (SINH), University of the Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS), Shanghai, China.

Background And Aims: Insulin receptor (IR) transduces cell surface signal through phosphoinositide 3-kinase (PI3K)-AKT pathways or translocates to the nucleus and binds to the promoters to regulate genes associated with insulin actions, including de novo lipogenesis (DNL). Chronic activation of IR signaling drives malignant transformation, but the underlying mechanisms remain poorly defined. Down-regulation of fructose-1,6-bisphosphate aldolase (ALDO) B in hepatocellular carcinoma (HCC) is correlated with poor prognosis. We aim to study whether and how ALDOB is involved in IR signaling in HCC.

Approach And Results: Global or liver-specific ALDOB knockout (L-ALDOB ) mice were used in N-diethylnitrosamine (DEN)-induced HCC models, whereas restoration of ALDOB expression was achieved in L-ALDOB mice by adeno-associated virus (AAV). C -glucose was employed in metabolic flux analysis to track the de novo fatty acid synthesis from glucose, and nontargeted lipidomics and targeted fatty acid analysis using mass spectrometry were performed. We found that ALDOB physically interacts with IR and attenuates IR signaling through down-regulating PI3K-AKT pathways and suppressing IR nuclear translocation. ALDOB depletion or disruption of IR/ALDOB interaction in ALDOB mutants promotes DNL and tumorigenesis, which is significantly attenuated with ALDOB restoration in L-ALDOB mice. Notably, attenuated IR/ALDOB interaction in ALDOB-R46A mutant exhibits more significant tumorigenesis than releasing ALDOB/AKT interaction in ALDOB-R43A, whereas knockdown IR sufficiently diminishes tumor-promoting effects in both mutants. Furthermore, inhibiting phosphorylated AKT or fatty acid synthase significantly attenuates HCC in L-ALDOB mice. Consistently, ALDOB down-regulation is correlated with up-regulation of IR signaling and DNL in human HCC tumor tissues.

Conclusions: Our study reports a mechanism by which loss of ALDOB activates IR signaling primarily through releasing IR/ALDOB interaction to promote DNL and HCC, highlighting a potential therapeutic strategy in HCC.
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http://dx.doi.org/10.1002/hep.32064DOI Listing
July 2021

Long non‑coding RNA DANCR represses the viability, migration and invasion of multiple myeloma cells by sponging miR‑135b‑5p to target KLF9.

Mol Med Rep 2021 Sep 19;24(3). Epub 2021 Jul 19.

Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.

Multiple myeloma (MM) is a malignancy of plasma cells that leads to marrow failure and bone lesions. Numerous studies have verified the link between long non‑coding RNAs (lncRNAs) and MM. The present study aimed to examine the role and underlying mechanism of differentiation antagonizing non‑protein coding RNA (DANCR) in MM cells. The relative expression levels of DANCR, microRNA (miR)‑135b‑5p and Krüppel‑like factor 9 (KLF9) were examined using reverse transcription‑quantitative PCR. Cell viability was assessed using the MTT assay, while relative cell migration and invasion were evaluated using Transwell assays. Moreover, the dual‑luciferase reporter assay was used to examine the interplay between DANCR, miR‑135b‑5p and KLF9. Western blotting was performed to determine the expression level of KLF9. It was found that lncRNA DANCR and KLF9 were downregulated, while miR‑135b‑5p was upregulated in the serum of patients with MM and in MM cells compared with the controls. Overexpressing DANCR or knocking down miR‑135b‑5p reduced the viability of the MM cells, as well as restrained MM cells from migrating and invading. Furthermore, DANCR directly targeted miR‑135b‑5p and was negatively correlated with miR‑135b‑5p. It was also found that KLF9 was targeted by miR‑135b‑5p and was inversely correlated with miR‑135b‑5p expression. The impact of lncRNA DANCR‑mediated suppression on cell viability, invasion and migration was partially abolished by short hairpin RNA KLF9 or miR‑135b‑5p mimics transfection in MM cells. Thus, it was suggested that lncRNA DANCR repressed the viability, migration and invasion of MM cells by sponging miR‑135b‑5p to target KLF9.
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http://dx.doi.org/10.3892/mmr.2021.12288DOI Listing
September 2021

Direct Quantification and Visualization of Homocysteine, Cysteine, and Glutathione in Alzheimer's and Parkinson's Disease Model Tissues.

Anal Chem 2021 07 6;93(28):9878-9886. Epub 2021 Jul 6.

Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, China.

Alzheimer's disease (AD) and Parkinson's disease (PD) are chronic neurodegenerative diseases with high morbidity and mortality. Homocysteine (Hcy), cysteine (Cys), and glutathione (GSH) are closely related to AD and PD. However, the dynamics of Hcy, Cys, and GSH in the brain tissues and the potential pathogenesis between Cys/Hcy/GSH with AD and PD remain unclear. Herein, a novel fluorescent probe with multiple binding sites was rationally designed and exploited for the direct quantification of serum total Hcy and Cys along with superior optical properties. Importantly, differentiation and simultaneity fluorescence imaging of Cys, Hcy, and GSH dynamics were achieved in living cells, tissues, and mouse models of AD and PD with this probe, providing direct evidences for the relationship between Hcy/Cys/GSH and AD/PD for the first time. In addition, pathogenesis studies demonstrated that elevated Hcy and Cys levels are closely related to imbalanced redox homeostasis, increased amyloid aggregates, and nerve cell cytotoxicity. These findings will greatly promote the understanding of the functions of Hcy/Cys/GSH in Alzheimer's and Parkinson's diseases, demonstrating clinical promise for the early diagnosis and prevention of AD and PD.
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http://dx.doi.org/10.1021/acs.analchem.1c01945DOI Listing
July 2021

Incidence and risk factors of late-onset hemorrhagic cystitis after single umbilical cord blood transplantation with myeloablative conditioning regimen.

Int J Hematol 2021 Sep 12;114(3):381-389. Epub 2021 Jun 12.

Department of Hematology of Anhui Provincial Hospital, Anhui Medical University, Hefei, China.

Objective: To explore the incidence and risk factors of late-onset hemorrhagic cystitis (LOHC) in patients undergoing single umbilical cord blood transplantation for hematological malignancies.

Methods: Clinical data from 234 patients who consecutively underwent single UCBT using a myeloablative conditioning regimen without antithymocyte globulin in our center were retrospectively analyzed.

Results: In total, 64 (27.4%) patients developed LOHC with a median onset time of 40.5 (range 8-154) days, and 15 (6.4%) patients gradually developed grade III-IV LOHC. The incidence of LOHC was marginally higher in adults (31.0%) than in children (23.7%) (p = 0.248). HLA matching ≤ 6/8 (HR = 2.624, 95% CI 1.112-6.191, p = 0.028) was an independent risk factor for LOHC. The overall survival of LOHC patients (59.8%, 95% CI 61.7-85.5%) was significantly lower than that of patients without LOHC (86.8%, 95% CI 79.6-91.6%) at 130 days post transplantation (p = 0.036).

Conclusion: Patients with less well-matched grafts have a higher incidence of LOHC. Inherent deficiencies in immunity in the context of HLA disparity and more intense pharmacologic immunosuppression after severe acute graft-versus-host disease may contribute to viral activation. Prevention and treatment of LOHC have the potential to prolong long-term survival.
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http://dx.doi.org/10.1007/s12185-021-03168-wDOI Listing
September 2021

The Advantages of Connectivity Map Applied in Traditional Chinese Medicine.

Front Pharmacol 2021 11;12:474267. Epub 2021 Mar 11.

School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Amid the establishment and optimization of Connectivity Map (CMAP), the functional relationships among drugs, genes, and diseases are further explored. This biological database has been widely used to identify drugs with common mechanisms, repurpose existing drugs, discover the molecular mechanisms of unknown drugs, and find potential drugs for some diseases. Research on traditional Chinese medicine (TCM) has entered a new era in the wake of the development of bioinformatics and other subjects including network pharmacology, proteomics, metabolomics, herbgenomics, and so on. TCM gradually conforms to modern science, but there is still a torrent of limitations. In recent years, CMAP has shown its distinct advantages in the study of the components of TCM and the synergetic mechanism of TCM formulas; hence, the combination of them is inevitable.
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http://dx.doi.org/10.3389/fphar.2021.474267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991830PMC
March 2021

Capturing noroviruses circulating in the population: sewage surveillance in Guangdong, China (2013-2018).

Water Res 2021 May 1;196:116990. Epub 2021 Mar 1.

Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China. Electronic address:

Noroviruses (NoVs) are the leading cause of acute gastroenteritis (AGE) outbreaks. Since 2014, novel genetic variants of NoV have been continuously identified and have caused a sharp increase in the number of AGE outbreaks. The specific geographical distribution and expanding genetic diversity of NoV has posed a challenge to conventional surveillance. Here, we describe the long-term dynamic correlation between NoV distribution in sewage and in the local population through the molecular surveillance of NoV in Guangdong, 2013-2018. The relative viral loads of the GI and GII genotypes in sewage were calculated through RT-PCR. A high-throughput sequencing method and operational taxonomic unit (OTU) clustering pipeline were developed to illustrate the abundances of different genotypes and genetic variants in sewage. Our results showed that the NoV viral loads and the emergence of new variants in sewage were closely associated with NoV outbreak risks in the population. Compared with the outbreaks surveillance, the dominance of the newly emerged variants, GII.P17-GII.17 and GII.P16-GII.2, could be detected one or two months ahead in sewage of a hub city. In addition, the dynamics of pre-epidemic variants, which were rarely detected in clinics, could be captured through sewage surveillance, thus improving our understanding of the origin and evolution of these novel epidemic variants. Our data highlight that sewage surveillance could provide nearly real-time and high-throughput data on NoV circulation in the community. With the advances in sequencing techniques, the sewage surveillance system could also be extended to other related infectious diseases.
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http://dx.doi.org/10.1016/j.watres.2021.116990DOI Listing
May 2021

Exosomal MiR-1290 Promotes Angiogenesis of Hepatocellular Carcinoma via Targeting SMEK1.

J Oncol 2021 29;2021:6617700. Epub 2021 Jan 29.

Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin 300071, China.

Hepatocellular carcinoma (HCC), the most common primary liver cancer, relies on the formation of new blood vessel for growth and frequent intrahepatic and extrahepatic metastasis. Therefore, it is important to explore the underlying molecular mechanisms of tumor angiogenesis of HCC. Recently, microRNAs have been shown to modulate angiogenic processes by modulating the expression of critical angiogenic factors. However, the potential roles of tumor-derived exosomal microRNAs in regulating tumor angiogenesis remain to be elucidated. In this study, our miRNome sequencing demonstrated that miR-1290 was overexpressed in HCC patient serum-derived exosomes, and we found that delivery of miR-1290 into human endothelial cells enhanced their angiogenic ability. Our results further revealed that SMEK1 is a direct target of miR-1290 in endothelial cells. MiR-1290 exerted its proangiogenic function, at least in part, by alleviating the inhibition of VEGFR2 phosphorylation done by SMEK1. Collectively, our findings provide evidence that miR-1290 is overexpressed in HCC and promotes tumor angiogenesis via exosomal secretion, implicating its potential role as a therapeutic target for HCC.
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http://dx.doi.org/10.1155/2021/6617700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864765PMC
January 2021

A Freestanding 3D Heterostructure Film Stitched by MOF-Derived Carbon Nanotube Microsphere Superstructure and Reduced Graphene Oxide Sheets: A Superior Multifunctional Electrode for Overall Water Splitting and Zn-Air Batteries.

Adv Mater 2020 Dec 19;32(48):e2003313. Epub 2020 Oct 19.

Nanomaterials Centre, School of Chemical Engineering and Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, 4072, Australia.

Developing a scalable approach to construct efficient and multifunctional electrodes for the hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and oxygen reduction reaction (ORR) is an urgent need for overall water splitting and zinc-air batteries. In this work, a freestanding 3D heterostructure film is synthesized from a Ni-centered metal-organic framework (MOF)/graphene oxide. During the pyrolysis process, 1D carbon nanotubes formed from the MOF link with the 2D reduced graphene oxide sheets to stitch the 3D freestanding film. The results of the experiments and theoretical calculations show that the synergistic effect of the N-doped carbon shell and Ni nanoparticles leads to an optimized film with excellent electrocatalytic activity. Low overpotentials of 95 and 260 mV are merely needed for HER and OER, respectively, to reach a current density of 10 mA cm . In addition, a high half-wave potential of 0.875 V is obtained for the ORR, which is comparable to that of Pt/RuO and ranks among the top of non-noble-metal catalysts. The use of an "all-in-one" film as the electrode leads to excellent performance of the homemade water electrolyzer and zinc-air battery, indicating the potential of the film for practical applications.
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http://dx.doi.org/10.1002/adma.202003313DOI Listing
December 2020

Jagged1-Notch1-deployed tumor perivascular niche promotes breast cancer stem cell phenotype through Zeb1.

Nat Commun 2020 10 12;11(1):5129. Epub 2020 Oct 12.

Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, 300071, Tianjin, China.

Zinc finger E-box binding homeobox 1 (Zeb1) has been demonstrated to participate in the acquisition of the properties of cancer stem cells (CSCs). However, it is largely unknown how signals from the tumor microenvironment (TME) contribute to aberrant Zeb1 expression. Here, we show that Zeb1 depletion suppresses stemness, colonization and the phenotypic plasticity of breast cancer. Moreover, we demonstrate that, with direct cell-cell contact, TME-derived endothelial cells provide the Notch ligand Jagged1 (Jag1) to neighboring breast CSCs, leading to Notch1-dependent upregulation of Zeb1. In turn, ectopic Zeb1 in tumor cells increases VEGFA production and reciprocally induces endothelial Jag1 in a paracrine manner. Depletion of Zeb1 disrupts this positive feedback loop in the tumor perivascular niche, which eventually lessens tumor initiation and progression in vivo and in vitro. In this work, we highlight that targeting the angiocrine Jag1-Notch1-Zeb1-VEGFA loop decreases breast cancer aggressiveness and thus enhances the efficacy of antiangiogenic therapy.
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http://dx.doi.org/10.1038/s41467-020-18860-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552407PMC
October 2020

Effect of Durio zibethinus rind polysaccharide on functional constipation and intestinal microbiota in rats.

Food Res Int 2020 10 16;136:109316. Epub 2020 May 16.

National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng 475004, China; Joint International Research Laboratory of Food & Medicine Resource Function, Henan Province, Kaifeng 475004, China. Electronic address:

The prevalence of constipation increases rapidly with the increased pressure of some people's life, which seriously affects the quality of life in related patients. In this study, the improvement of functional constipation by Durio zibethinus Murr rind polysaccharide (DZMP) and the effects of DZMP on intestinal microbiota were investigated in a constipation model of Sprague-Dawley (SD) rats established by loperamide hydrochloride. Results showed that DZMP at 200 mg/kg could significantly (P < 0.05) increase the intestinal transit rate, motilin, gastrin, substance P levels and concentration of short-chain fatty acids (SCFAs), reduce the somatostatin levels and improve the gastrointestinal peristalsis of rats. Sequencing showed that the Lachnospiraceae-NK4A136-group in the rats given 200 mg/kg DZMP (16.07%) was significantly higher than that of the model group (10.13%), while the Desulfovibrio was lower (2.99%) than that of the model group (4.19%). Principal co-ordinates analysis (PcoA) revealed a significant difference in intestinal microbiota composition between the model group and the high-dose DZMP group (200 mg/kg). The results demonstrated that DZMP has a regulatory effect of treating functional constipation and regulating intestinal flora in rats.
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http://dx.doi.org/10.1016/j.foodres.2020.109316DOI Listing
October 2020

Effects of Polysaccharide from Koehne Flowers in Cyclophosphamide-Induced Immunosuppression and Oxidative Stress on Mice.

Oxid Med Cell Longev 2020 12;2020:1603735. Epub 2020 Mar 12.

National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng, 475004 Henan, China.

The immunomodulatory effects of flower polysaccharide (MHFP) were investigated in this paper. The model of immunosuppressive mice was established by cyclophosphamide, which was treated with different dosages of MHFP (600, 400, and 200 mg/kg·d). The results showed that MHFP significantly increased the index of the spleen and thymus and improved the atrophy of immune organs. MHFP enhanced the ability of carbon clearance and phagocytosis of mononuclear phagocytes in mice. Meanwhile, MHFP promoted the proliferation of splenic lymphocytes. MHFP could enhance the content of serum hemolysin and improve the decrease of hemolysin induced by cyclophosphamide. The contents of ACP and LDH in the serum and spleen were determined, indicating that MHFP could enhance the activity of macrophages. MHFP promoted the content of cytokines (IL-2, IL-6, TNF-, and IFN-) and mRNA expression. At the same time, the pathological changes of the spleen tissue also showed that MHFP could improve the immunosuppression induced by cyclophosphamide. In addition, MHFP increased the content of SOD, T-AOC, and CAT in the serum and spleen tissue, decreased the level of MDA, and improved the oxidative stress caused by cyclophosphamide. In conclusion, MHFP could effectively improve the immunosuppression and oxidative stress induced by cyclophosphamide and enhance the immune capacity of mice.
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http://dx.doi.org/10.1155/2020/1603735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091559PMC
December 2020

The expression of interleukin-25 increases in human coronary artery disease and is associated with the severity of coronary stenosis.

Anatol J Cardiol 2020 Feb;23(3):151-159

Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology; Wuhan-China.

Objective: Interleukin (IL) 25, also known as IL-17E, is an inflammatory cytokine and has been demonstrated to be closely related to cardiovascular diseases by regulating immunity and inflammation, including atherosclerosis. This study was aimed to evaluate the expression of IL-25 in patients with coronary artery disease (CAD).

Methods: In this study, the expression of IL-25 in normal (n=6) and atherosclerotic (n=10) human coronary arteries was detected by immunofluorescent staining. In addition, the serum IL-25, IL-6, and tumor necrosis factor (TNF) α concentrations in stable angina pectoris (SAP, n=44), unstable angina pectoris (UAP, n=46), acute myocardial infarction (AMI, n=34), and non-CAD (control, n=36) were measured using enzyme-linked immunosorbent assay (ELISA) kits.

Results: IL-25 was significantly increased in coronary arteries of CAD patients when compared with normal coronary arteries, with macrophages and T lymphocytes being the sources of IL-25, especially macrophages. Moreover, the serum concentrations of IL-25 were markedly elevated in CAD patients and gradually increased in SAP, UAP, and AMI groups. In addition, IL-25 levels were positively correlated with the IL-6 and TNF-α levels, and Gensini score in CAD patients. Logistic regression analysis showed that IL-25 was independently positively correlated with the occurrence of acute coronary syndrome (ACS). A receiver operator characteristic curve suggested that IL-25 presented a significant diagnosis value in ACS.

Conclusion: IL-25 is increased in the coronary arteries and serum of CAD patients and is associated with the severity of coronary stenosis and the occurrence of ACS, suggesting that IL-25 may be one of the biomarkers of ACS.
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http://dx.doi.org/10.14744/AnatolJCardiol.2019.24265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222637PMC
February 2020

ADAMTS-5 Decreases in Coronary Arteries and Plasma from Patients with Coronary Artery Disease.

Dis Markers 2019 16;2019:6129748. Epub 2019 Dec 16.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.

The current study demonstrates that a disintegrin and metalloproteinase with thrombospondin type 1 motif- (ADAMTS-) 5 is a key extracellular matrix protease and associated with cardiovascular diseases. However, the plasma ADAMTS-5 levels and relevance of coronary artery disease (CAD) remain largely unknown. This study is aimed at examining the relationship between the plasma ADAMTS-5 levels and the severity of coronary stenosis in patients with CAD. In the present study, the expression of ADAMTS-5 was analyzed in coronary artery samples and blood. The results showed that the plasma ADAMTS-5 levels were lower in the CAD group than in the control group. In addition, significantly higher matrix metalloproteinase- (MMP-) 2 and MMP-9 levels were also observed in the patients with CAD, and the ADAMTS-5 levels were negatively correlated with the MMP-2 and MMP-9 levels. Spearman's correlation analysis showed that the Gensini score was negatively correlated with the ADAMTS-5 levels but was positively correlated with the MMP-2 and MMP-9 levels. Receiver-operating characteristic (ROC) analysis revealed that ADAMTS-5, MMP-2, and MMP-9 may have a certain diagnostic value in CAD and that the combination of all three metalloproteinases had a higher diagnostic value. The findings provided a better understanding of the role of ADAMTS-5 in the diagnosis of CAD.
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http://dx.doi.org/10.1155/2019/6129748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935801PMC
May 2020

Correction: PPA1 promotes NSCLC progression via a JNK- and TP53-dependent manner.

Oncogenesis 2019 Dec 13;8(12):75. Epub 2019 Dec 13.

Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin, 300071, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41389-019-0184-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923412PMC
December 2019

Exercise Protects Sympathetic Stress-Induced Myocardial Fibrosis by Regulating Cytokines.

J Cardiovasc Transl Res 2020 08;13(4):570-571

School of Medicine (in preparation), Shanghai University, Shanghai, 200444, China.

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http://dx.doi.org/10.1007/s12265-019-09933-xDOI Listing
August 2020

The TRPA1 Channel in the Cardiovascular System: Promising Features and Challenges.

Front Pharmacol 2019 18;10:1253. Epub 2019 Oct 18.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

The transient receptor potential ankyrin 1 (TRPA1) channel is a calcium-permeable nonselective cation channel in the plasma membrane that belongs to the transient receptor potential (TRP) channel superfamily. Recent studies have suggested that the TRPA1 channel plays an essential role in the development and progression of several cardiovascular conditions, such as atherosclerosis, heart failure, myocardial ischemia-reperfusion injury, myocardial fibrosis, arrhythmia, vasodilation, and hypertension. Activation of the TRPA1 channel has a protective effect against the development of atherosclerosis. Furthermore, TRPA1 channel activation elicits peripheral vasodilation and induces a biphasic blood pressure response. However, loss of channel expression or blockade of its activation suppressed heart failure, myocardial ischemia-reperfusion injury, myocardial fibrosis, and arrhythmia. In this paper, we review recent research progress on the TRPA1 channel and discuss its potential role in the cardiovascular system.
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http://dx.doi.org/10.3389/fphar.2019.01253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813932PMC
October 2019

PPA1 promotes NSCLC progression via a JNK- and TP53-dependent manner.

Oncogenesis 2019 Sep 24;8(10):53. Epub 2019 Sep 24.

Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin, 300071, China.

Inorganic pyrophosphatase (PPA1) promotes tumor progression in several tumor types. However, the underlying mechanism remains elusive. Here, we disclosed that PPA1 expression is markedly upregulated in lung carcinoma tissue versus normal lung tissue. We also found that the non-small cell lung cancer (NSCLC) cell lines show increased PPA1 expression levels versus normal lung cell line control. Moreover, the knockdown of PPA1 promotes cell apoptosis and inhibits cell proliferation. Whereas, the ectopic expression of PPA1 reduces cell apoptosis and enhances cell proliferation. Most interestingly, the expression of mutant PPA1 (D117A) significantly abolishes PPA1-mediated effect on cell apoptosis and proliferation. The underlying mechanism demonstrated that TP53 expression deficiency or JNK inhibitor treatment could abolish PPA1-mediated NSCLC progression. In summary, the aforementioned findings in this study suggest a new pathway the PPA1 mediates NSCLC progression either via TP53 or JNK. Most important, the pyrophosphatase activity is indispensible for PPA1-mediated NSCLC progression. This may provide a promising target for NSCLC therapy.
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http://dx.doi.org/10.1038/s41389-019-0162-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760234PMC
September 2019

A novel polysaccharide from Malus halliana Koehne with coagulant activity.

Carbohydr Res 2019 Nov 10;485:107813. Epub 2019 Sep 10.

National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng, 475004, China; Kaifeng Key Laboratory of Functional Components in Health Food, Kaifeng, 475004, China. Electronic address:

A novel polysaccharide in Malus halliana Koehne, named MHP-W, was isolated and purified by DEAE-52 cellulose and Sephadex G-100 columns. Structural features were identified by high performance size-exclusion chromatography (HPSEC), fourier transform infrared (FT-IR) spectrometer, gas chromatography (GC) and (1D & 2D) NMR Spectroscopy. Structural characterization showed that the molecular weight of MHP-W was 353 kDa composed of arabinose, xylose, mannose, glucose and galactose in a molar ratio of 2.59: 0.15: 0.23: 0.25: 9.70. The existence of β-glycosidic bond between the sugar units was confirmed by FT-IR and NMR spectroscopy. The effects of MHP-W on active part thrombin time (APTT), protothrombin time (PT), thrombin time (TT), and fibrinogen (FIB) were screened by a cell-based coagulation activity model. MHP-W could significantly shorten TT (p < 0.001) and increase FIB (p < 0.05) as compared with the control group. The results showed that MHP-W promoted bloodclotting through endogenous and exogenous coagulation pathways as well as increasing fibrinogen content, which indicated that MHP-W had procoagulant activities in vitro.
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http://dx.doi.org/10.1016/j.carres.2019.107813DOI Listing
November 2019

Interleukin-5 levels are decreased in the plasma of coronary artery disease patients and inhibit Th1 and Th17 differentiation in vitro.

Rev Esp Cardiol (Engl Ed) 2020 May 6;73(5):393-402. Epub 2019 Sep 6.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiovascular Research Institute, Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China. Electronic address:

Introduction And Objectives: Interleukin (IL)-5 is an anti-inflammatory cytokine that has been demonstrated to be involved in cardiovascular diseases, including aortic aneurysm and heart failure. This study aimed to investigate the involvement of IL-5 in coronary artery disease (CAD) and the possible mechanisms.

Methods: We analyzed IL-5 expression in human coronary artery specimens collected from CAD patients and deceased donors. Plasma IL-5, IL-17, and interferon-γ levels in CAD patients were detected using ELISA kits, with samples from chest pain patients (non-CAD) as controls. Mouse CD4T helper (Th) cells were separated, and the effect of IL-5 on Th1, regulatory T cell and Th17 differentiation and mRNA levels of their characteristic cytokines were detected using flow cytometry and reverse transcription-quantitative polymerase chain reaction, respectively.

Results: IL-5 was significantly decreased in the coronary plaque of CAD patients compared with the deceased donors group, and IL-5 was mainly derived from macrophages in the coronary artery plaque. Compared with the non-CAD group, plasma IL-5 levels in the CAD groups were significantly lower, and the sequence from high to low was stable angina pectoris, unstable angina pectoris, and acute myocardial infarction. Binary linear regression analysis showed that IL-5 was independently correlated with the occurrence of CAD. Recombinant mouse IL-5 treatment decreased Th1 and Th17 levels and mRNA expression of their characteristic cytokines in oxidized low-density lipoprotein-treated CD4Th cells.

Conclusion: IL-5 levels were decreased in CAD patients and inhibited oxidized low-density lipoprotein Th1 and Th17 differentiation in vitro.
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http://dx.doi.org/10.1016/j.rec.2019.07.005DOI Listing
May 2020

Increased Interleukin-11 Levels Are Correlated with Cardiac Events in Patients with Chronic Heart Failure.

Mediators Inflamm 2019 8;2019:1575410. Epub 2019 Jan 8.

Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan 430060, China.

Background: Interleukin-11 (IL-11) is an important inflammatory cytokine and has been demonstrated to participate in cardiovascular diseases. However, there have been no studies about the role of IL-11 in heart failure (HF). The present study is aimed at investigating whether IL-11 levels are associated with the cardiac prognosis in patients with HF.

Methods: The plasma concentrations of IL-11 were measured in 240 patients with chronic HF (CHF) and 80 control subjects without signs of significant heart disease. In addition, we prospectively followed these CHF patients to endpoints of cardiac events.

Results: Compared with the control group, the plasma IL-11 concentrations were significantly increased in the CHF patients and gradually increased in the New York Heart Association (NYHA) functional class II group, the NYHA functional class III group, and the NYHA functional class IV group. The receiver operating characteristic (ROC) curve revealed that the predictive role of IL-11 in HF is not as good as N-terminal B-type natriuretic peptide (BNP), although IL-11 has a certain value in predicting cardiac events. In addition, the CHF patients were divided into 3 groups according to the plasma IL-11 concentration category (low, T1; middle, T2; and high, T3). The multivariate Cox hazard analysis showed that the high plasma IL-11 concentrations were independently associated with the presence of cardiac events after adjustment for confounding factors. Furthermore, the CHF patients were divided into two groups based on the median plasma IL-11 concentrations. The Kaplan-Meier analysis revealed that the patients with high IL-11 concentrations had a higher risk of cardiac events compared with those with low IL-11 concentrations.

Conclusions: Higher plasma IL-11 levels significantly increase the presence of cardiac events and suggest a poor outcome; although the diagnostic value of IL-11 in CHF is not as good as BNP, there is a certain value in predicting cardiac events in CHF.
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http://dx.doi.org/10.1155/2019/1575410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341241PMC
August 2019

Corrigendum to "TRPA1 inhibition ameliorates pressure overload-induced cardiac hypertrophy and fibrosis in mice" [EBioMedicine (2018) 54-62].

EBioMedicine 2018 12 9;38:292. Epub 2018 Nov 9.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China. Electronic address:

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http://dx.doi.org/10.1016/j.ebiom.2018.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306367PMC
December 2018

Interleukin-12p35 knockout promotes macrophage differentiation, aggravates vascular dysfunction, and elevates blood pressure in angiotensin II-infused mice.

Cardiovasc Res 2019 05;115(6):1102-1113

Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China.

Aims: Numerous studies have demonstrated that inflammation is involved in the progression of hypertension. Inflammatory cytokines interleukin (IL)-12 and IL-35 belong to the IL-12 cytokine family and share the same IL-12p35 subunit. Accumulating evidence has demonstrated that IL-12p35 knockout (IL-12p35 KO) leads to cardiovascular disease by regulating the inflammatory response. This study aimed to investigate whether IL-12p35 KO elevates blood pressure in a hypertension mouse model.

Methods And Results: Mice with angiotensin (Ang) II infusion showed marked aortic IL-12p35 expression; thus, aortic macrophages may be the main source of IL-12p35. Wild-type and IL-12p35 KO mice were infused with Ang II or saline. IL-12p35 KO promoted M1 macrophage differentiation, amplified the inflammatory response, aggravated vascular dysfunction, and elevated blood pressure in Ang II-treated mice. Then, some Ang II-infused mice were given phosphate buffer saline, mouse recombinant IL-12 (rIL-12), or rIL-35, and the results showed that rIL-12 but not rIL-35 treatment had an antihypertensive effect on Ang II-infused mice. In addition, detection of human plasma IL-12 levels in hypertensive patients and control subjects showed that IL-12 was significantly increased in hypertensive patients when compared with control subjects. In hypertensive patients, IL-12 levels were positively correlated with blood pressure.

Conclusion: IL-12p35 KO amplifies the inflammatory response and promotes blood pressure elevation in Ang II-treated mice. In addition, IL-12, but not IL-35, plays a protective role in the Ang II-induced hypertension model. Thus, IL-12 may be a novel therapeutic agent for the prevention and treatment of clinical hypertension.
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http://dx.doi.org/10.1093/cvr/cvy263DOI Listing
May 2019

TRPA1 inhibition ameliorates pressure overload-induced cardiac hypertrophy and fibrosis in mice.

EBioMedicine 2018 Oct 5;36:54-62. Epub 2018 Oct 5.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China. Electronic address:

Background: Recent evidence has indicated that the transient receptor potential ankyrin 1 (TRPA1) is expressed in the cardiovascular system and implicated in the development and progression of several cardiovascular diseases. However, the effects of TRPA1 on cardiac hypertrophy development remain unclear. The aim of this study was to determine the role of TRPA1 in cardiac hypertrophy and fibrosis development.

Methods: C57BL/6J mice were subjected to transverse aortic constriction (TAC) and were orally treated with the TRPA1 selective inhibitors HC-030031 (HC) and TCS-5861528 (TCS). Morphological assessments, echocardiographic parameters, histological analyses and flow cytometry were used to evaluate cardiac hypertrophy and fibrosis.

Results: Human and mouse hypertrophic hearts presented with noticeably increased TRPA1 protein levels. Inhibition of TRPA1 by HC and TCS attenuated cardiac hypertrophy and preserved cardiac function after chronic pressure overload, as evidenced by increased heart weight/body weight ratio, cardiomyocyte cross-sectional area and mRNA expression of hypertrophic markers, including ANP, BNP and β-MHC. Dramatic interstitial fibrosis was observed in the mice subjected to TAC surgery, and this was markedly attenuated in the HC and TCS treated mice. Mechanistically, the results revealed that TRPA1 inhibition ameliorated pressure overload-induced cardiac hypertrophy by negatively regulating Ca/calmodulin-dependent protein kinase II (CaMKII) and calcineurin signaling pathways. We also demonstrated that blocking TRPA1 decreased the proportion of M2 macrophages and reduced profibrotic cytokine levels, thereby improving cardiac fibrosis.

Conclusions: TRPA1 inhibition protected against cardiac hypertrophy and suppressed cardiac dysfunction via Ca-dependent signal pathways and inhibition of the M2 macrophages transition. These results suggest that TRPA1 may represent a potential therapeutic drug target for cardiac hypertrophy and fibrosis.
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http://dx.doi.org/10.1016/j.ebiom.2018.08.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197736PMC
October 2018

Interleukin-12p35 Knock Out Aggravates Doxorubicin-Induced Cardiac Injury and Dysfunction by Aggravating the Inflammatory Response, Oxidative Stress, Apoptosis and Autophagy in Mice.

EBioMedicine 2018 Sep 15;35:29-39. Epub 2018 Sep 15.

Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, and Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, China. Electronic address:

Background: Recent evidence has demonstrated that interleukin 12p35 knockout (IL-12p35 KO) is involved in cardiac diseases by regulating the inflammatory response. The involvement of inflammatory cells has also been observed in doxorubicin (DOX)-induced cardiac injury. This study aimed to investigate whether IL-12p35 KO affects DOX-induced cardiac injury and the underlying mechanisms.

Methods: First, the effect of DOX treatment on cardiac IL-12p35 expression was assessed. In addition, to investigate the effect of IL-12p35 KO on DOX-induced cardiac injury, IL-12p35 KO mice were treated with DOX. Because IL-12p35 is the mutual subunit of IL-12 and IL-35, to determine the cytokine that mediates the effect of IL-12p35 KO on DOX-induced cardiac injury, mice were given phosphate-buffered saline (PBS), mouse recombinant IL-12 (rIL-12) or rIL-35 before treatment with DOX.

Results: DOX treatment significantly increased the level of cardiac IL-12p35 expression. In addition, IL-12p35 KO mice exhibited higher serum and heart lactate dehydrogenase levels, higher serum and heart creatine kinase myocardial bound levels, and greater cardiac dysfunction than DOX-treated mice. Furthermore, IL-12p35 KO further increased M1 macrophage and decreased M2 macrophage differentiation, aggravated the imbalance of oxidants and antioxidants, and further activated the mitochondrial apoptotic pathway and endoplasmic reticulum stress autophagy pathway. Both rIL-12 and rIL-35 protected against DOX-induced cardiac injury by alleviating the inflammatory response, oxidative stress, apoptosis and autophagy.

Conclusions: IL-12p35 KO aggravated DOX-induced cardiac injury by amplifying the levels of inflammation, oxidative stress, apoptosis and autophagy. (234 words).
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http://dx.doi.org/10.1016/j.ebiom.2018.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154773PMC
September 2018

Erratum to "Anti-Interleukin-22-Neutralizing Antibody Attenuates Angiotensin II-Induced Cardiac Hypertrophy in Mice".

Mediators Inflamm 2018 26;2018:2586494. Epub 2018 Aug 26.

Department of Cardiology, Hubei Key Laboratory of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China.

[This corrects the article DOI: 10.1155/2017/5635929.].
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http://dx.doi.org/10.1155/2018/2586494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129352PMC
August 2018

Increased kielin/chordin-like protein levels are associated with the severity of heart failure.

Clin Chim Acta 2018 Nov 23;486:381-386. Epub 2018 Aug 23.

Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan 430060, China. Electronic address:

Background: Previous studies demonstrated that the transforming growth factor (TGF) β superfamily, including TGF-βs and bone morphogenetic proteins (BMPs), plays important roles in cardiovascular diseases. The kielin/chordin-like protein (KCP) is a secreted protein that regulates the expression and function of TGF-βs and BMPs. However, the role of KCP during heart failure (HF) remains unknown. The present study aimed to investigate the cardiac expression of KCP in human failing hearts.

Methods: The human failing heart samples from patients with dilated cardiomyopathy (DCM, n = 12) and ischemic cardiomyopathy (ICM, n = 12) were collected, and normal heart (n = 8) samples from unmatched donors were collected as controls. Collagen volume, KCP levels, and mRNA levels of several BMPs in left ventricles (LV) of all hearts were measured.

Results: The KCP levels were significantly higher in human failing hearts than in normal hearts. KCP levels were positively associated with hypertrophy markers, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC). In addition, KCP levels were also positively associated with left ventricular end-diastolic dimension (LVEDD), collagen Iα and collagen IIIα expression but were negatively associated with left ventricular ejection fraction (LVEF). Furthermore, increased TGF-β1, BMP2/4/6/10 and reduced BMP7 levels were observed, and positive correlations between KCP and TGF-β1 and negative correlation between KCP and BMP2/7 were found, but not for BMP4/6/10.

Conclusions: KCP was closely associated with heart failure. The regulation of BMP2/7 and TGF-β1 expression may be the possible mechanisms.
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http://dx.doi.org/10.1016/j.cca.2018.08.033DOI Listing
November 2018

Serum Levels of Complement-C1q/Tumor Necrosis Factor-Related Protein-3 Decreased in Patients With Acute Aortic Dissection.

Am J Cardiol 2018 10 4;122(7):1244-1248. Epub 2018 Jul 4.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiovascular Research Institute of Wuhan University, Wuhan, China; Hubei Key Laboratory of Cardiology, Wuhan, China. Electronic address:

Complement-C1q/tumor necrosis factor-related protein-3 (CTRP3) is one kind of adipocytokines and has been reported to play key roles in many cardiovascular diseases by regulating inflammation. Inflammation was reported to be involved in the development of acute aortic dissection (AAD). The purpose of this study was to investigate whether serum levels of CTRP3 were associated with AAD. The serum was collected from 108 participants, including 60 patients with AAD and 32 patients with hypertension, as well as 16 healthy subjects. Serum levels of CTRP3, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured using enzyme-linked immunosorbent assay kits. Decreased serum levels of CTRP3 were found in AAD patients compared with hypertension and healthy subjects (35.89 ± 11.26 vs 52.60 ± 13.90 and 51.71 ± 18.64 ng/mL, p < 0.001, respectively). IL-6 and TNF-α levels were significantly higher in AAD patients than those in hypertension and healthy subjects (IL-6: 31.33 ± 15.18 vs 13.13 ± 8.63 and 9.40 ± 6.27 pg/mL, p < 0.001; TNF-α: 36.87 ± 11.16 vs 29.66 ± 5.12 and 22.93 ± 7.18 pg/mL, p < 0.001, respectively). In AAD, CTRP3 levels showed a negative correlation with IL-6 and TNF-α levels respectively (r = -0.508, p < 0.001; r = -0.393, p = 0.002, respectively). In conclusion, decreased levels of CTRP3 may be associated with the development of AAD.
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http://dx.doi.org/10.1016/j.amjcard.2018.06.024DOI Listing
October 2018

Ophiopogonin B suppresses the metastasis and angiogenesis of A549 cells in vitro and in vivo by inhibiting the EphA2/Akt signaling pathway.

Oncol Rep 2018 Sep 27;40(3):1339-1347. Epub 2018 Jun 27.

School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing 210023, P.R. China.

Lung adenocarcinoma is the most common metastatic cancer, and is associated with high patient mortality. Therefore, investigation of anti‑metastatic treatments for lung adenocarcinoma is crucial. Ophiopogonin B (OP‑B) is a bioactive component of Radix Ophiopogon Japonicus, which is often used in Chinese traditional medicine to treat pulmonary disease. Screening of transcriptome and digital gene expression (DGE) profiling data in NSCLC cell lines showed that OP‑B regulated the epithelial‑mesenchymal transition (EMT) pathway in A549 cells. Further results showed that 10 µmol/l OP‑B downregulated EphA2 expression and phosphorylation (Ser897) in A549 cells but upregulated them in NCI‑H460 cells. Meanwhile, the Ras/ERK pathway was unaffected in A549 cells and stimulated in NCI‑H460 cells. More importantly, detection of the EMT pathway showed that OP‑B treatment increased the epithelial markers ZO‑1 and E‑cadherin and decreased the expression of the mesenchymal marker N‑cadherin and the transcriptional repressors Snail, Slug and ZEB1. Furthermore, through Transwell migration and scratch wound healing assays, we found that 10 µmol/l OP‑B significantly reduced the invasion and migration of A549 cells. In vivo, we found that 75 mg/kg OP‑B inhibited A549 cell metastasis in a pulmonary metastasis nude mouse model. In addition, we also found that 10 µmol/l OP‑B significantly inhibited tube formation in EA.hy926 cells. The expression of VEGFR2 and Tie‑2, the phosphorylation of Akt (S473) and PLC (S1248), and the levels of EphA2 and phosphorylated EphA2 (S897) were all inhibited by OP‑B in this cell line. In vivo, using a Matrigel plug assay, we found that OP‑B inhibited angiogenesis and the hemoglobin content of A549 transplanted tumors. Taken together, OP‑B inhibited the metastasis and angiogenesis of A549 cells by inhibiting EphA2/Akt and the corresponding pathway. The investigation gives new recognition to the anticancer mechanism of OP‑B in NSCLC and this compound is a promising inhibitor of metastasis and angiogenesis of lung adenocarcinoma cells.
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http://dx.doi.org/10.3892/or.2018.6531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072400PMC
September 2018

Epigenetic dysregulation of ZEB1 is involved in LMO2-promoted T-cell acute lymphoblastic leukaemia leukaemogenesis.

Biochim Biophys Acta Mol Basis Dis 2018 Aug 17;1864(8):2511-2525. Epub 2018 May 17.

Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin 300071, China. Electronic address:

T-cell acute lymphoblastic leukaemia (T-ALL) is a hematological malignancy caused by the accumulation of genomic lesions that affect the development of T-cells. ZEB1, a member of zinc finger-homeodomain family transcription factor, exhibits crucial function in promoting T-cell differentiation and potentially acts as a tumor suppressor in T-ALL. However, the molecular mechanism by which ZEB1 regulates T-ALL leukaemogenesis remains obscure. Here, we showed that oncogenic LIM only 2 (LMO2) could recruit Sap18 and HDAC1 to assemble an epigenetic regulatory complex, thus inducing histone deacetylation in ZEB1 promoter and chromatin remodeling to achieve transcriptional repression. Furthermore, downregulation of ZEB1 by LMO2 complex results in an increased leukaemia stem cell (LSC) phenotype as well as unsensitivity in response to methotrexate (MTX) chemotherapy in T-ALL cells. Importantly, we demonstrated that Trichostatin A (TSA, a HDAC inhibitor) addition significantly attenuates MTX unsensitivity caused by dysfunction of LMO2/ZEB1 signaling. In conclusion, these findings have identified a molecular mechanism underlying LMO2/ZEB1-mediated leukaemogenesis, paving a way for treating T-ALL with a new strategy of epigenetic inhibitors.
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http://dx.doi.org/10.1016/j.bbadis.2018.05.013DOI Listing
August 2018
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