Cun Zhang

Air Force Medical University

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Yingqi Zhang

Air Force Medical University

Qiang Hao

Air Force Medical University

Weina Li

Sichuan University

Xiaochang Xue

Shaanxi Normal University

Meng Li

Guangzhou Medical University

Wangqian Zhang

Air Force Medical University

Shuning Wang

Air Force Medical University

Yuan Gao

Wuhan University of Science and Technology

Wei Zhang

Emory University

Kuo Zhang

Yanshan University

Cooperative Institutions

Air Force Medical University

167

Chinese Academy of Sciences

Xijing Hospital

Anhui Medical University

Chinese Academy of Medical Sciences & Peking Union Medical College

Nanjing Medical University

First Affiliated Hospital of Anhui Medical University

Peking University

Sichuan University

Sun Yat-sen University

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Acetylation and Amination Protect Angiotensin 1–7 from Physiological Hydrolyzation and Therefore Increases Its Antitumor Effects on Lung Cancer

Molecular Pharmaceutics (2018)

Xiaowen Ma Zhijun Pang Jiming Zhou Lei He Qiang Hao

The recently reported inhibitory effects of angiotensin 1–7 (Ang-(1–7)) on various cancers indicate its potential use as a therapeutic agent for primary and metastatic cancers. However, its extremely short half-life in the circulation greatly compromises its potential applications. Here, we reported an Ang-(1–7) analogue peptide with the amino and carboxy termini protected by acetylation and amination. The in vitro and in vivo degradation of the resulting analogue, Ang-AA, were determined using high-performance liquid chromatography (HPLC). At the same time, small RNA interference and competition studies were performed to evaluate the specific capacity of Ang-AA to bind to the cell surface Mas receptor. Cell Counting Kit-8 (CCK8), wound-healing, and Boyden chamber assays were performed to investigate the inhibitory effects of Ang-AA on A549 cells. Finally, the synergistic inhibitory effects of Ang-AA and paclitaxel (PTX) on A549 xenografts in mice were observed using animal imaging systems and survival observations. The toxicity of Ang-AA in mice was evaluated. Our results showed that acetylation and amination significantly inhibited the hydrolyzation of Ang-(1–7) in vitro and in vivo. The half-life of Ang-(1–7) in rats was prolonged from 2.4 ± 0.6 min to 238.7 ± 61.3 min (p < 0.001). The specific binding of Ang-AA to the Mas receptor was well preserved, and Ang-AA exerted significantly greater inhibitory effects on the proliferation, migration, and invasion of A549 cells than Ang-(1–7). The combination of Ang-AA and PTX exhibited a significantly greater synergistic inhibitory effect on A549 xenografts than the combination of Ang-(1–7) and PTX. Ang-AA did not display obvious toxicity in mice. Our findings indicate acetylation and amination is a simple and effective method for producing Ang-(1–7) as a bioactive peptide.

10.1021/acs.molpharmaceut.8b00181

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FOXP3 inhibits cancer stem cell self-renewal via transcriptional repression of COX2 in colorectal cancer cells

Oncotarget (2017)

Shuo Liu Cun Zhang Kuo Zhang Yuan Gao Zhaowei Wang

Colon cancer stem cell (cCSC) is considered as the seed cell of colon cancer initiation and metastasis. Cyclooxygenase-2 (COX2), a downstream target of NFκB, is found to be essential in promoting cancer stem cell renewal. However, how COX2 is dysregulated in cCSCs is largely unknown. In this study, we found that the expression of transcription factor FOXP3 was much lower in the spheroids than that in the parental tumor cells. Overexpression of FOXP3 significantly decreased the numbers of spheres, reduced the side population. Accordingly, FOXP3 expression decreased the tumor size and weight in the xenograft model. The tumor inhibitory effects of FOXP3 were rarely seen when COX2 was additionally knocked down. Mechanically, FOXP3 transcriptionally repressed COX2 expression via interacting with and thus inhibiting p65 activity on the putative NFκB response elements in COX2 promoter. Taken together, we here revealed possible involvement of FOXP3 in regulating cCSC self-renewal via tuning COX2 expression, and thus providing a new target for the eradication of colon cancer stem cells.

Zhàng

10.18632/oncotarget.17974

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Citations (21)

Optimization of initial dosage of quetiapine in schizophrenic patients: effects of fluvoxamine or duloxetine coadministration

Frontiers in Pharmacology (2024)

Xiaohong Chen Yue Zhang Yin Di Yanjun Jin Su‐Mei He

Although quetiapine has been approved for use in schizophrenic patients, its individualized dosage regimen remains unclear, especially with respect to drug-drug interactions (DDIs). Thus, we investigated the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on population pharmacokinetics (PPK).

Fluvoxamine

Quetiapine Fumarate

Duloxetine Hydrochloride

10.3389/fphar.2024.1496043

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Citations (1)

CXCL12+ Tumor-associated Endothelial Cells Promote Immune Resistance in Hepatocellular Carcinoma.

Journal of Hepatology (2024)

Yajie Lu Yunpeng Liu Xiaoshuang Zuo G F Li Jianlin Wang

10.1016/j.jhep.2024.09.044

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Citations (4)

Selective Functional Hyperconnectivity in the Middle Temporal Gyrus Subregions in Lifelong Premature Ejaculation

The Journal of Sexual Medicine (2020)

Tingting Zhang Dongdong Tang Huanhuan Cai Biao Zhang Ying Yang

Middle temporal gyrus

Parahippocampal gyrus

10.1016/j.jsxm.2020.05.006

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Construction, Expression, and Characterization of Thymosin Alpha 1 Tandem Repeats inEscherichia coli

BioMed Research International (2013)

Xiaochang Xue Zhen Yan Weina Li Meng Li Xin Qin

Thymosin alpha 1 (T α 1), which is composed of 28 amino acids, has been commercialized worldwide for its immune-modulatory and antitumor effects. T α 1 can stimulate T cell proliferation and differentiation from bone marrow stem cells, augment cell-mediated immune responses, and regulate homeostasis of immune system. In this study, we developed a novel strategy to produce T α 1 concatemer (T α 1③) in Escherichia coli and compared its activity with chemically synthesized T α 1. Results showed that T α 1③can more effectively stimulate T cell proliferation and significantly upregulate IL-2 receptor expression. We concluded that the expression system for T α 1 concatemer was constructed successfully, which could serve as an efficient tool for the production of large quantities of the active protein.

Concatemer

Thymosin

Alpha (finance)

10.1155/2013/720285

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Citations (5)

Rapid Propagation of Pelargonium graveolens in Vitro

Xibei Linxueyuan xuebao (2003)

Cun Zhang NW Sci

One year stem section was used as explants to established shoots. Sterile shoots and leaves were used to induce callus basing on MS basic medium containing low levels of a cytokinin and an auxin. Following shoot differentiation and proliferation on the callus, the microshoots were rooted in low salt media containing low level of an auxin. 100% rooting ratio was obtained. Rooted plants were transplanted into pots containing a mixture of sand and humus. Over 95% plants survived the transfer.

Callus

Pelargonium

Geraniaceae

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Transmural Dispersion of Action Potential Duration and Heterogeneous Changes of L Type Calcium Current in Rabbit Heart Three Months After Myocardial Infarction.

The Chinese Journal of Cardiac Pacing and Electrophysiology (2002)

Cun Zhang

During chronic,healed (three months) stage after myocardial infarction (OMI),structural and electrical remodeling of regions remote from the infarct plays an important role in arrhythmogenesis.We measured transmural dispersion of action potential duration (TD APD) in vitro,and studied changes of L type calcium current (I Ca,L ) of epimyocyte (Epi),midmyocyte (M) and endomyocyte (Endo) in region remote from infarcted zone.Results:We found that myocytes remote from infarct were hypertrophied and remodeled,APDs of three layers myocytes were lengthened,APD of Endo was shortest compared with Epi and M cell ( P 0.01).TD APD was significantly increased (OMI group 288.32±19.56 vs Sham group 228.45±13.94,Control group 210.32±17.43 ms, P 0.01).I Ca,L density was decreased in OMI group,the reduction of I Ca,L density was most prominent in Endo (at +10 mV,from 16.12±1.60 to 10.73±0.06 pA/pF,decreased 33.43% vs Epi from 16.59±0.50 to 11.75±0.69 pA/pF,decreased 29.17%,M from 18.70±1.03 to 13.27± 1.05 pA/pF ,decreased 29.03%, P 0.05).Conclusions:Our data suggest that the changes of TD APD and I Ca,L density in myocytes of region remote from infract zone are heterogeneous and are very susceptibility to develop reentrant arrhythmias.

Border zone

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Hapten and antiserum for parathion immunoassay

Nanjing Nongye Daxue xuebao (2002)

Cun Zhang

Conjugates of reduced parathion and its modified metabolits to bovine serum album via diazo coupling were used as antigens to inject the rabbits.The antiserum produced showed special sensitivity to the parathion in the enzyme linked immunosorbent assay,binding and inhibition experiments,which demonstrated that the lowest limited concentration is as low as 0 1 ng·mL -1 and the I 50 is 5 2 ng·mL -1 in the condition of pH 7 4.Cross experiments showed that the polyclonantibody in the serum was very high active to parathion,much less to the reduced paration,and little to other metabolits,Metho parathion,P nitrophenol.

Hapten

Parathion

Parathion methyl

Conjugate

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Knockout of microRNA‑26a promotes lung development and pulmonary surfactant synthesis

Molecular Medicine Reports (2018)

Yifan Sun Qing Kan Yang Yang Yinghui Zhang Jinxin Shen

Normal formation and function of the lungs are essential for the transition of the fetus to an air‑breathing environment at birth. The synthesis of pulmonary surfactant (PS), which is produced by type II alveolar epithelial cells (AECIIs), is required for proper lung development. Previous in vitro studies have suggested that PS synthesis is regulated by microRNA (miR)‑26a in fetal rat AECIIs. The present study explored the potential role of miR‑26a in lung development and PS synthesis by using a miR‑26a‑1/miR‑26a‑2 double knockout mouse model. Hematoxylin and eosin staining and transmission electron microscopy were used to observe the morphology of fetal lungs. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein levels of surfactant‑associated proteins. The results demonstrated that the lung formation in the knockout mice was more mature, and that there were more mature lamellar bodies inside AECIIs in miR‑26a knockout mice at late stages of lung development. The findings further demonstrated that knockout of miR‑26a increased surfactant‑associated mRNA and protein expression levels. The results indicated that knockout of miR‑26a promotes lung development and PS synthesis.

Lamellar granule

Knockout mouse

Surfactant protein C

Conditional gene knockout

10.3892/mmr.2018.8602

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Citations (17)