Publications by authors named "Zhenfeng Chen"

21 Publications

  • Page 1 of 1

SIRT1 attenuates sepsis-induced acute kidney injury via Beclin1 deacetylation-mediated autophagy activation.

Cell Death Dis 2021 Feb 26;12(2):217. Epub 2021 Feb 26.

Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Baiyun District, Guangzhou, Guangdong, 510515, China.

Our previous studies showed that silent mating-type information regulation 2 homologue-1 (SIRT1, a deacetylase) upregulation could attenuate sepsis-induced acute kidney injury (SAKI). Upregulated SIRT1 can deacetylate certain autophagy-related proteins (Beclin1, Atg5, Atg7 and LC3) in vitro. However, it remains unclear whether the beneficial effect of SIRT1 is related to autophagy induction and the underlying mechanism of this effect is also unknown. In the present study, caecal ligation and puncture (CLP)-induced mice, and an LPS-challenged HK-2 cell line were established to mimic a SAKI animal model and a SAKI cell model, respectively. Our results demonstrated that SIRT1 activation promoted autophagy and attenuated SAKI. SIRT1 deacetylated only Beclin1 but not the other autophagy-related proteins in SAKI. SIRT1-induced autophagy and its protective effect against SAKI were mediated by the deacetylation of Beclin1 at K430 and K437. Moreover, two SIRT1 activators, resveratrol and polydatin, attenuated SAKI in CLP-induced septic mice. Our study was the first to demonstrate the important role of SIRT1-induced Beclin1 deacetylation in autophagy and its protective effect against SAKI. These findings suggest that pharmacologic induction of autophagy via SIRT1-mediated Beclin1 deacetylation may be a promising therapeutic approach for future SAKI treatment.
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http://dx.doi.org/10.1038/s41419-021-03508-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910451PMC
February 2021

Role of the Receptor for Advanced Glycation End Products in Heat Stress-Induced Endothelial Hyperpermeability in Acute Lung Injury.

Front Physiol 2020 7;11:1087. Epub 2020 Oct 7.

Department of Emergency and Critical Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Science, Guangzhou, China.

Objective: To study the role of the receptor for advanced glycation end products (RAGE) in endothelial barrier dysfunction induced by heat stress, to further explore the signal pathway by which RAGE contributes to heat-induced endothelia response, and thereby find a novel target for the clinical treatment of ALI (acute lung injury) induced by heatstroke.

Methods: This study established the animal model of heatstroke using RAGE knockout mice. We observed the role of RAGE in acute lung injury induced by heatstroke in mice by evaluating the leukocytes, neutrophils, and protein concentration in BALF (Bronchoalveolar lavage fluids), lung wet/dry ratio, histopathological changes, and the morphological ultrastructure of lung tissue and arterial blood gas analysis. To further study the mechanism, we established a heat stress model of HUVEC and concentrated on the role of RAGE and its signal pathway in the endothelial barrier dysfunction induced by heat stress, measuring Transendothelial electrical resistance (TEER) and western blot.

Results: RAGE played a key role in acute lung injury induced by heatstroke in mice. The mechanism C-Jun is located in the promoter region of the RAGE gene. C-Jun increased the RAGE protein expression while HSF1 suppressed RAGE protein expression. The overexpressed RAGE protein then increased HUVEC monolayer permeability by activating ERK and P38 MAPK under heat stress.

Conclusion: This study indicates the critical role of RAGE in heat stress-induced endothelial hyperpermeability in acute lung injury and suggests that RAGE could be a potential therapeutic target in protecting patients against acute lung injury induced by heatstroke.
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http://dx.doi.org/10.3389/fphys.2020.01087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643755PMC
October 2020

Efficacy and safety of acupoint injection therapy for allergic rhinitis: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2020 Oct;99(42):e22737

The first Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi Province, China.

Background: Allergic rhinitis (AR), characterized by nasal itching, sneezing, and congestion, is a common disorder of nose. In the United States, AR affects 10% to 20% of adults. The negative impact of the high prevalence of AR has caused a great economic burdens worldwide. Modern Western Medicine mainly treats AR with antihistamine drugs, glucocorticoids, allergic immunotherapy (AIT), but it seriously affects patients compliance because of its long course of treatment, high medical costs and side effect. And now, as an important mean of treating AR, acupoint injection has been widely used in clinics, and has achieved significant efficacy.

Methods And Analysis: The following databases will be searched for relevant information before July 2020: PubMed, Embase, Cochrane Library, Web of Science, and CNKI.

Major Results: scores of Rhinitis Quality of Life (RQLQ), Rhinitis Total Symptom Scores (RTSS). Secondary results: levels of antigen-specific serum immunoglobulin E (IgE), total effective rate, adverse event. Data will be collected independently by 2 researchers, and the risk of bias in meta-analysis will be evaluated according to "Cochrane Handbook for Systematic Reviews of Interventions". All data analysis will be conducted using Review Manager V.5.3. and Stata V.12.0.

Results: The curative effect and safety of acupoint injection treatment for AR patients will be evaluated systematically.

Conclusion: The systematic review of this study will summarize the currently published evidence of acupoint injection treatment for AR to further guide its promotion and application.

Ethics And Dissemination: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.Open Science Framework (OSF) registration number: https://osf.io/fa9dq.
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http://dx.doi.org/10.1097/MD.0000000000022737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572024PMC
October 2020

Protective effect of 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione, isolated from Averrhoa carambola L., against Aβ1-42-induced apoptosis in SH-SY5Y cells by reversing Bcl-2/Bax ratio.

Psychopharmacology (Berl) 2021 Jan 8;238(1):193-200. Epub 2020 Oct 8.

Department of Pharmacology, Guangxi Medical University, Nanning, 530021, People's Republic of China.

Background And Purpose: Aβ1-42-induced neurotoxicity has been considered as a possible mechanism to aggravate the onset and progression of Alzheimer's disease (AD). In this study, we aim to determine the protective effect of DMDD on the apoptosis of SH-SY5Y cells induced by Aβ1-42 and elucidate potential mechanism of DMDD's protective function in apoptosis.

Experimental Approach: CCK-8, AnnexinV-FITC/PI flow cytometry, and transmission electron microscopy analysis were used to determine the protection of DMDD on Aβ1-42-evoked apoptosis of SH-SY5Y cells. Cytochrome c release, JC-1 staining, and measuring the protein of Bcl-2 family by Western blot were applied to elucidate the mechanism of DMDD's protective function in apoptosis.

Key Results: Three concentration of DMDD (5 μmol/L, 10 μmol/L, and 20 μmol/L) rescues the cell viability loss and apoptosis of SH-SY5Y cells cultivated in Aβ1-42. The expressions of cleaved Caspase-3, -8, -9, the cytochrome c release, and mitochondrial membrane potential loss were inhibited by DMDD in Aβ1-42-insulted SH-SY5Y cells. The Western blot analysis showed that DMDD pretreatment clearly downregulated the protein of Bax and upregulated Bcl-2. Moreover, the Bcl-2/Bax ratio was obviously decreased in cells only exposed to Aβ1-42, but, which was suppressed by treated with DMDD.

Conclusion And Implications: DMDD attenuated the apoptosis of SH-SY5Y cells induced by Aβ1-42 through reversing the Bcl-2/Bax ratio.
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http://dx.doi.org/10.1007/s00213-020-05668-9DOI Listing
January 2021

Chinese herbal compound prescription for systemic lupus erythematosus: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2020 Oct;99(40):e22404

The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi Province.

Background: Systemic lupus erythematosus (SLE), known as lupus, is a chronic autoimmune disease and there is no cure for SLE. The western medication can improve syndromes to some extent; however, severe adverse drug reactions appear at the same time. Recently, it is confirmed that Chinese medicine also can have an excellent clinical efficacy on SLE.

Methods And Analysis: The following databases will be searched for relevant information before July 2020: PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure.

Major Results: levels of total remission rate, SLEDAI. Secondary results: The laboratory index about C3 levels, Hb levels, white blood cell levels, and adverse event. Data will be collected independently by 2 researchers, and the risk of bias in meta analysis will be evaluated according to "Cochrane Handbook for Systematic Reviews of Interventions." All data analysis will be conducted using Review Manager V.5.3. and Stata V.12.0.

Results: The curative effect and safety of Chinese herbal compound prescription treatment for SLE patients will be evaluated systematically.

Conclusion: The systematic review of this study will summarize the currently published evidence of Chinese herbal compound prescription treatment for SLE to further guide its promotion and application.

Ethics And Dissemination: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OPEN SCIENCE FRAMEWORK (OSF)REGISTRATION NUMBER:: https://osf.io/wvfrx/.
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http://dx.doi.org/10.1097/MD.0000000000022404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535673PMC
October 2020

Bifunctional Naphthoquinone Aromatic Amide-Oxime Derivatives Exert Combined Immunotherapeutic and Antitumor Effects through Simultaneous Targeting of Indoleamine-2,3-dioxygenase and Signal Transducer and Activator of Transcription 3.

J Med Chem 2020 02 17;63(4):1544-1563. Epub 2020 Feb 17.

State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China) , School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University , Guilin 541004 , China.

Indoleamine-2,3-dioxygenase 1 (IDO1) and signal transducer and activator of transcription 3 (STAT3) are important targets in the tumor microenvironment for cancer therapy. In the present study, a set of naphthoquinone aromatic amide-oxime derivatives were designed, which stimulated the immune response via IDO1 inhibition and simultaneously displayed powerful antitumor activity against three selected cancer cell lines through suppressing STAT3 signaling. The representative compound bound effectively to IDO1, with greater inhibitory activity relative to the commercial IDO1 inhibitor 4-amino--(3-chloro-4-fluorophenyl)-'-hydroxy-1,2,5-oxadiazole-3-carboximidamide () in addition to the efficient suppression of nuclear translocation of STAT3. Consistently, in vivo assays demonstrated a higher antiproliferative activity of compound in both wild-type B16-F10 isograft tumors and an athymic HepG2 xenograft model relative to 1-methyl-l-tryptophan () and doxorubicin (). This bifunctional compound with dual immunotherapeutic and anticancer efficacy may represent a new generation of highly efficacious drug candidates for cancer therapy.
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http://dx.doi.org/10.1021/acs.jmedchem.9b01386DOI Listing
February 2020

Dynamically Characterizing Skeletal Muscles via Acoustic Non-linearity Parameter: In Vivo Assessment for Upper Arms.

Ultrasound Med Biol 2020 02 8;46(2):315-324. Epub 2019 Nov 8.

The State Key Laboratory of Mechanical System and Vibration, School of Mechanical Engineering, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

It is crucial to model skeletal muscles for muscle-centered health care, such as prosthetics. Here we hypothesize that the acoustic non-linearity parameter (B/A) can be utilized to partially represent the contraction state of skeletal muscles. Although previous work commonly measured the B/A value of tissues in vitro, the present study targets the biceps brachii muscle to investigate the relationship between the B/A value and the dynamics of the elbow. Furthermore, it is proposed that a correction method based on the angular spectrum theory be applied in vivo, and the dynamic metrics of the B/A value and its feasibility be verified through an underwater experiment. Seven participants were invited for the in vivo experiment, in which elbow torque and B/A values were measured simultaneously. The non-plane reflection was approximately treated through an integral method, leading to a modified B/A value. Then, linear regression was applied to characterize the B/A-torque relationship, with the calculated coefficient of determination (R) ranging from 0.85-0.93. Experimental results indicate that the modified B/A value of the biceps brachii correlates well with elbow torque. This study not only paves the way to dynamic measurement of the B/A value of skeletal muscles in vivo, but also confirms that B/A can be used as a more comprehensive assessment criterion for muscle functions.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2019.08.007DOI Listing
February 2020

Polydatin protects against lipopolysaccharide-induced endothelial barrier disruption via SIRT3 activation.

Lab Invest 2020 04 22;100(4):643-656. Epub 2019 Oct 22.

Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

In a previous study, we demonstrated the role of polydatin (PD) in protecting against multiple organ dysfunction in sepsis. The aim of this study is to investigate whether PD protects against lipopolysaccharide (LPS)-induced endothelial barrier disruption through SIRT3 activation and to disclose the underlying mechanisms. Wild-type mice were injected with LPS and Evans Blue assay was performed to evaluate vascular permeability. Primary human umbilical vein endothelial cells (HUVECs) were stimulated with LPS. Endothelial permeability was evaluated by transendothelial electrical resistance (TER) and FITC-dextran leakage. SIRT3 activity was determined by a Deacetylase Fluorometric kit, and protein expression level of SIRT3 was detected by western blotting. Mitochondrial function was evaluated by determination of ROS level, mitochondrial membrane potential and mPTP opening. In endotoxemic mice, PD pretreatment attenuated vascular leakage in multiple organs while SIRT3 inhibition with 3-TYP reversed the effects of PD. PD treatment in late sepsis also exhibited barrier protective effects. In HUVECs, PD alleviated LPS-induced F-actin rearrangement, cadherin-catenin complex dissociation and endothelial hyperpermeability, whereas 3-TYP or SIRT3 siRNA attenuated the protective effects of PD. PD enhanced SIRT3 deacetylase activity, and attenuated LPS-induced decrease in SIRT3 expression as well. Furthermore, gain-of-function and loss-of-function strategies also confirmed the role of SIRT3 in enhancing endothelial barrier integrity. It was further ascertained that PD enhanced SIRT3-mediated deacetylation of SOD2 and cyclophilin D (CypD), thus suppressing mitochondrial dysfunction and subsequent endothelial barrier dysfunction. In addition, it was revealed that RAGE was involved in LPS-regulated SIRT3 signaling. Our results suggest that polydatin protects against LPS-induced endothelial barrier disruption dependent on SIRT3 and can be applied as a potential therapy for sepsis.
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http://dx.doi.org/10.1038/s41374-019-0332-8DOI Listing
April 2020

β-Catenin phosphorylation at Y654 and Y142 is crucial for high mobility group box-1 protein-induced pulmonary vascular hyperpermeability.

J Mol Cell Cardiol 2019 02 25;127:174-184. Epub 2018 Dec 25.

Department of Pathophysiology, Key Laboratory for Shock and Microcirculation Research of Guangdong Province, Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China. Electronic address:

Objective: Endothelial hyperpermeability is a hallmark of acute lung injury in response to sepsis. The imbalance between adherence junction (AJ) mediated cell-cell adherence forces and stress fiber driven contractile forces contributes to increased endothelial permeability. Here, we spotlight the effects of β-catenin Y654 andY142 phosphorylation on HMGB1-mediated endothelial barrier leakage.

Approach And Results: Our results showed that phospho-deficiencies at both β-catenin Y654and Y142ameliorated pulmonary vascular dysfunction in male C57 mice receiving a cecal ligation and puncture operation. In vitro analysis indicated that high mobility group box-1 protein (HMGB1) triggered β-catenin Y654 and Y142 phosphorylation, causing β-catenin translocation and adherence junction (AJ) disruptions as well as cytoskeleton rearrangement. In addition,β-catenin Y654 dephosphorylation attenuated HMGB1-mediated dissociation of VE-cadherin/β-catenin and, hence, partially prevented endothelial hyperpermeability. β-catenin Y142 dephosphorylation abolished HMGB1-induced uncoupling of β-catenin and α-catenin, suppressed cytoskeletal reassembly and, hence, alleviated endothelial hyperpermeability. Further investigation demonstrated that RAGE and Src were required forβ-catenin Y654 phosphorylation in response to HMGB1, while FAK was responsible for HMGB1-triggered β-catenin Y142 phosphorylation.

Conclusions: In sum, this study revealed the role of β-catenin Y654 and Y142 phosphorylation in HMGB1-mediated endothelial hyperpermeability through dysregulation between adherence and contractile forces. This result advances understanding of the mechanisms underlying pulmonary vascular hyperpermeability in sepsis.
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http://dx.doi.org/10.1016/j.yjmcc.2018.12.012DOI Listing
February 2019

Mitochondrion-Targeting Identification of a Fluorescent Apoptosis-Triggering Molecule by Mass Spectrometry Elucidates Drug Tracking.

Chembiochem 2019 03 1;20(6):778-784. Epub 2019 Feb 1.

State Key Laboratory for Chemistry and, Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, P.R. China.

The real-time tracking of localization and dynamics of small molecules in organelles helps to understand their function and identification of their potential targets at subcellular resolution. To identify the mitochondrion-targeting effects of small molecules (NA-17 and NA-2a) in cancer cells, we used mass spectrometry to study their distribution and accumulation in mitochondria and in the surrounding cytoplasm thus enabling tracing of action processes of therapeutic compounds. Colocalization analysis with the aid of imaging agents suggests that both NA-17 and NA-2a display mitochondrion-targeting effects. However, MS analysis reveals that only NA-2a displays both a mitochondrion-targeting effect and an accumulation effect, whereas NA-17 only distributes in the surrounding cytoplasm. A combination of mitochondrion imaging, immunoblotting, and MS analysis in mitochondria indicated that NA-17 neither has the ability to enter mitochondria directly nor displays any mitochondrion-targeting effect. Further studies revealed that NA-17 could not enter into mitochondria even when the mitochondrial permeability in cells changed after NA-17 treatment, as was evident from reactive oxygen species (ROS) generation and cytochrome c release. In the process of cellular metabolism, NA-17 itself is firmly restricted to the cytoplasm during the metabolic process, but its metabolites containing fluorophores could accumulate in mitochondria for cell imaging. Our studies have furnished new insights into the drug metabolism processes.
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http://dx.doi.org/10.1002/cbic.201800598DOI Listing
March 2019

Protective Effects of 2-Dodecyl-6-Methoxycyclohexa-2,5 -Diene-1,4-Dione Isolated from Averrhoa Carambola L. (Oxalidaceae) Roots on Neuron Apoptosis and Memory Deficits in Alzheimer's Disease.

Cell Physiol Biochem 2018 7;49(3):1064-1073. Epub 2018 Sep 7.

Department of Pharmacology, Guangxi Medical University, Nanning, China.

Background/aims: The roots of Averrhoa carambola L. (Oxalidaceae) have long been used as a traditional Chinese medicine for the treatment of headaches, vomiting, coughing and hangovers. 2-dodecyl-6-methoxycyclohexa-2, 5-1, 4-dione (DMDD) has been isolated from A. carambola L. roots, and this study was carried out to investigate the potential beneficial effects of DMDD on neuron apoptosis and memory deficits in Alzheimer's disease.

Methods: The effects of a DMDD on learning and memory in APP/PS1 transgenic AD mice in vivo were investigated via Morris water maze and Y-type electric maze tests. In vitro, Cell viability was assessed by CCK-8. Apoptosis was assessed by Annexin V-FITC/PI flow cytometry assay, and transmission electron microscopy assay. Relative quantitative real-time PCR and Western blot were used to determine the expressions of genes and proteins.

Results: The spatial learning and memory deficit, fear memory deficit, as well as apoptosis and loss of neuron in hippocampal area of APP/PS1 mice were reversed by DMDD in APP/PS1 transgenic AD mice. DMDD protected against the Aβ1-42-induced apoptosis, loss of mitochondria membrane potential, induction of pro-apoptotic Bcl-2 family protein Bax, reduction of anti-apoptotic Bcl-2 family proteins Bcl-2, and activation of Caspase-3, and -9 in PC-12 cells. The Bcl-2/Bax ratio was also increased in DMDD-pretreated PC-12 cells in vitro and APP/PS1 mice in vivo.

Conclusion: DMDD has potential benefit on treating learning and memory deficit in APP/PS1 transgenic AD mice, and its effects may be associated with reversing the apoptosis of neuron via inhibiting Bax/Bcl-2 mediated mitochondrial membrane potential loss.
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http://dx.doi.org/10.1159/000493289DOI Listing
October 2018

A Small β-Carboline Derivative "B-9-3" Modulates TGF-β Signaling Pathway Causing Tumor Regression .

Front Pharmacol 2018 19;9:788. Epub 2018 Jul 19.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.

Targeting tumor microenvironment (TME) is crucial in order to overcome the anti-cancer therapy resistance. In this study, we report the antitumor activity of a newly synthesized β-carboline derivative "B-9-3." Here, this small molecule showed a promising antitumor activity along with an enhanced immune response as reflected by a reduction of regulatory T cells and increased CD4+/CD8+ T cells. Further, B-9-3 decreased the number of myofibroblasts not only in the tumor but also in the lung suggesting an anti-metastatic action. The reduction of myofibroblasts was associated with lower expression of epithelial-to-mesenchymal transition markers and a decrease of phosphorylated SMAD2/3 complex indicating the implication of TGF-β signaling pathway in B-9-3's effect. The blockade of myofibroblasts induction by B-9-3 was also verified in human fibroblasts treated with TGF-β. To elucidate the mechanism of B-9-3's action on TGF-β pathway, first, we investigated the molecular interaction between B-9-3 and TGF-β receptors using docking method. Data showed a weak interaction of B-9-3 with the ATP-binding pocket of TGFβRI but a strong one with a ternary complex formed of extracellular domains of TGFβRI, TGFβRII, and TGF-β. In addition, the role of TGFβRI and TGFβRII in B-9-3's activity was explored . B-9-3 did not decrease any of the two receptors' protein level and only reduced phosphorylated SMAD2/3 suggesting that its effect was more probably due to its interaction with the ternary complex rather than decreasing the expression of TGF-β receptors or interfering with their ATP-binding domains. B-9-3 is a small active molecule which acts on the TGF-β signaling pathway and improves the TME to inhibit the proliferation and the metastasis of the tumor with the potential for clinical application.
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http://dx.doi.org/10.3389/fphar.2018.00788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063040PMC
July 2018

Src Plays an Important Role in AGE-Induced Endothelial Cell Proliferation, Migration, and Tubulogenesis.

Front Physiol 2018 21;9:765. Epub 2018 Jun 21.

Key Laboratory for Shock and Microcirculation Research of Guangdong Province, Department of Pathophysiology, Southern Medical University, Guangzhou, China.

Advanced glycation end products (AGEs), produced by the non-enzymatic glycation of proteins and lipids under hyperglycemia or oxidative stress conditions, has been implicated to be pivotal in the development of diabetic vascular complications, including diabetic retinopathy. We previously demonstrated that Src kinase played a causative role in AGE-induced hyper-permeability and barrier dysfunction in human umbilical vein endothelial cells (HUVECs). While the increase of vascular permeability is the early event of angiogenesis, the effect of Src in AGE-induced angiogenesis and the mechanism has not been completely revealed. Here, we investigated the impact of Src on AGE-induced HUVECs proliferation, migration, and tubulogenesis. Inhibition of Src with inhibitor PP2 or siRNA decreased AGE-induced migration and tubulogenesis of HUVECs. The inactivation of Src with pcDNA3/flag-Src also restrained AGE-induced HUVECs proliferation, migration, and tube formation, while the activation of Src with pcDNA3/flag-Src enhanced HUVECs angiogenesis alone and exacerbated AGE-induced angiogenesis. AGE-enhanced HUVECs angiogenesis was accompanied with the phosphorylation of ERK in HUVECs. The inhibition of ERK with its inhibitor PD98059 decreased AGE-induced HUVECs angiogenesis. Furthermore, the inhibition and silencing of Src suppressed the AGE-induced ERK activation. And the silencing of AGEs receptor (RAGE) inhibited the AGE-induced ERK activation and angiogenesis as well. In conclusions, this study demonstrated that Src plays a pivotal role in AGE-promoted HUVECs angiogenesis by phosphorylating ERK, and very likely through RAGE-Src-ERK pathway.
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http://dx.doi.org/10.3389/fphys.2018.00765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021521PMC
June 2018

A Novel Naphthalimide Compound Restores p53 Function in Non-small Cell Lung Cancer by Reorganizing the Bak·Bcl-xl Complex and Triggering Transcriptional Regulation.

J Biol Chem 2016 Feb 14;291(8):4211-25. Epub 2015 Dec 14.

From the State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin 541004, China

p53 inactivation is a hallmark in non-small-cell lung cancer (NSCLC). It is therefore highly desirable to develop tumor-specific treatment for NSCLC therapy by restoring p53 function. Herein, a novel naphthalimide compound, NA-17, was identified as a promising drug candidate in view of both its anticancer activity and mechanism of action. NA-17 exhibited strong anticancer activity on a broad range of cancer cell lines but showed low toxicity to normal cell lines, such as HL-7702 and WI-38. Moreover, NA-17 showed p53-dependent inhibition selectivity in different NSCLC cell lines due to the activation state of endogenous p53 in the background level. Further studies revealed that NA-17 caused cell cycle arrest at the G1 phase, changed cell size, and induced apoptosis and cell death by increasing the proportion of sub-G1 cells. Molecular mechanism studies suggested that targeted accumulation of phospho-p53 in mitochondria and nuclei induced by NA-17 resulted in activation of Bak and direct binding of phospho-p53 to the target DNA sequences, thereby evoking cell apoptosis and cell cycle arrest and eventually leading to irreversible cancer cell inhibition. This work provided new insights into the molecular interactions and anticancer mechanisms of phospho-p53-dependent naphthalimide compounds.
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http://dx.doi.org/10.1074/jbc.M115.669978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4759195PMC
February 2016

Adaptive neural control of MIMO nonlinear systems with a block-triangular pure-feedback control structure.

IEEE Trans Neural Netw Learn Syst 2014 Nov;25(11):2017-29

This paper presents adaptive neural tracking control for a class of uncertain multiinput-multioutput (MIMO) nonlinear systems in block-triangular form. All subsystems within these MIMO nonlinear systems are of completely nonaffine pure-feedback form and allowed to have different orders. To deal with the nonaffine appearance of the control variables, the mean value theorem is employed to transform the systems into a block-triangular strict-feedback form with control coefficients being couplings among various inputs and outputs. A systematic procedure is proposed for the design of a new singularity-free adaptive neural tracking control strategy. Such a design procedure can remove the couplings among subsystems and hence avoids the possible circular control construction problem. As a consequence, all the signals in the closed-loop system are guaranteed to be semiglobally uniformly ultimately bounded. Moreover, the outputs of the systems are ensured to converge to a small neighborhood of the desired trajectories. Simulation studies verify the theoretical findings revealed in this paper.
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http://dx.doi.org/10.1109/TNNLS.2014.2302856DOI Listing
November 2014

Antioxidant Activities of Plumbagin and Its Cu (II) Complex.

Bioinorg Chem Appl 2011 23;2011:898726. Epub 2011 Oct 23.

Department of Chemistry and Biology, Yulin Normal College, Yulin 537000, China.

Plumbagin and its Cu (II) complex [Cu (plumbagin)(2)]·H(2)O have been synthesized, and their antioxidant activities towards the inhibitory effect on DPPH free radical, reducing power, total antioxidant capacity, and inhibition on lipid peroxidation were investigated. Plumbagin and its Cu (II) complex were found to exhibit scavenging activities on DPPH radical with the inhibitory rate of 41% and 24%, respectively. The reducing power of plumbagin was outstanding at the concentrations of 1.0, 1.5, and 2.0 mg/mL, compared to Cu (II) complex and synthetic antioxidant 2,6-di-ter-butyl-4-methylphenol (BHT); the highest level reached 1.333 for plumbagin and 0.581 for Cu (II) complex. Also, the inhibition on lipid peroxidation of plumbagin was higher than that of Cu (II) complex and BHT, 46.4% for plumbagin and 24.5% for Cu (II) complex. The results give a strong impact for designing anticancer drugs, combined with their potential cytotoxic and antioxidant activities, which can be targeted selectively against cancer cells and increase their therapeutic index and additional advantages over other anticancer drugs.
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http://dx.doi.org/10.1155/2011/898726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199187PMC
November 2011

Synthesis and antioxidant activities of novel 4-Schiff base-7-benzyloxy-coumarin derivatives.

Bioorg Med Chem Lett 2011 Nov 16;21(22):6811-5. Epub 2011 Sep 16.

Department of Chemistry, Guilin Normal College, Guangxi 541001, PR China.

4-Schiff base-7-benzyloxy-coumarins 5a(1)-5h(2) and its derivative 6 were designed and synthesized based on the 7-benzyloxy-coumarin structure as novel antioxidants. The in vitro antioxidant activities screening revealed that 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities of compounds 5b(1), 5d(1), 5f(1), 5f(2), 5g(1) and 5g(2), and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) cation (ABTS(+)) radical scavenging activities of compounds 5a(1), 5b(1), 5c(1), 5c(2), 5d(1), 5e(1), 5e(2), 5f(2), 5g(1), 5g(2) and 5h(1) were better than that of the commercial antioxidant butylated hydroxytoluene (BHT), while the superoxide anion radical scavenging activities of 5a(2) and 5g(2) were stronger than that of the commercial antioxidant butylated hydroxyanisole (BHA), and the hydroxyl radical scavenging activity of 5e(1) was much better than that of the common antioxidant ascorbic acid.
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http://dx.doi.org/10.1016/j.bmcl.2011.09.029DOI Listing
November 2011

Synthesis, cytotoxic activity, and DNA binding properties of copper (II) complexes with hesperetin, naringenin, and apigenin.

Bioinorg Chem Appl 2009 8:347872. Epub 2009 Oct 8.

The Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Chemical Engineering, Guangxi Normal University, Guilin 541004, China.

Complexes of copper (II) with hesperetin, naringenin, and apigenin of general composition [CuL(2)(H(2)O)(2)] nH(2)O (1-3) have been synthesized and characterized by elemental analysis, UV-Vis, FT-IR, ESI-MS, and TG-DTG thermal analysis. The free ligands and the metal complexes have been tested in vitro against human cancer cell lines hepatocellular carcinoma (HepG-2), gastric carcinomas (SGC-7901), and cervical carcinoma (HeLa). Complexes 1 and 3 were found to exhibit growth inhibition of SGC-7901 and HepG2 cell lines with respect to the free ligands; the inhibitory rate of complex 1 is 43.2% and 43.8%, while complex 3 is 46% and 36%, respectively. The interactions of complex 1 and its ligand Hsp with calf thymus DNA were investigated by UV-Vis, fluorescence, and CD spectra. Both complex 1 and Hsp were found to bind DNA in intercalation modes, and the binding affinity of complex 1 was stronger than that of free ligand.
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http://dx.doi.org/10.1155/2009/347872DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760321PMC
June 2010

Studies on the interaction of cinnamic acid with bovine serum albumin.

Chem Pharm Bull (Tokyo) 2007 Jun;55(6):871-5

College of Chemistry and Chemical Engineering, Guangxi Normal University, Guilin, Guangxi, People's Republic of China.

The interaction between cinnamic acid and bovine serum albumin (BSA) have been studied at three temperatures, 296, 303 and 310 K. Fluorescence quenching spectra in combination with Fourier transform infrared (FT-IR) spectroscopy and circular dichroism (CD) spectroscopy was used to investigate the drug-binding mode, the binding constant and the protein structure changes in the presence of cinnamic acid in aqueous solution at pH 7.40. The fluorescence quenching constant K(q), K(sv) and the binding constant K were calculated according to Stern-Volmer equation based on the quenching of the fluorescence of BSA in the presence of cinnamic acid. The thermodynamic parameters, the enthalpy (DeltaH) and the entropy change (DeltaS) were estimated to be -16.457 kJ mol(-1) and 38.028 J mol(-1) K(-1) according to the van't Hoff equation. The displacement experiment shows that cinnamic acid can bind to the subdomain IIA (corresponding to Sudlow's drug binding site I). The distance between the tryptophan residues in BSA and cinnamic acid bound to site I was estimated to be 1.63 nm using Föster's equation on the basis of fluorescence energy transfer. The decreased binding constant in the presence of common ions indicates that common ions have effect on drug-BSA system.
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http://dx.doi.org/10.1248/cpb.55.871DOI Listing
June 2007

Study of the interaction of indirubin with bovine serum albumin.

Chem Pharm Bull (Tokyo) 2006 Sep;54(9):1239-43

College of Chemistry and Chemical Engineering, Guangxi Normal University, Guilin, Guangxi 51004, People's Republic of China.

This study examined the interaction of indirubin with bovine serum albumin (BSA) at three temperatures (286, 297, 308 K) at pH 7.40. In the presence of indirubin, the drug-BSA binding mode, binding constant and the protein structure changes in aqueous solution were determined by fluorescence quenching methods including Fourier transform infrared (FT-IR) spectroscopy and UV-Vis spectroscopy. The FT-IR change indicates that indirubin binds to BSA. The change in protein secondary structure accompanying ligand binding has been proved by fluorescence spectra data. The thermodynamic parameters, the enthalpy change (DeltaH), and the entropy change (DeltaS) calculated by the van't Hoff equation possess small negative (-2.744 kJ.mol(-1)) and positive values (112.756 J.mol(-1).K(-1)), respectively, which indicated that hydrophobic interactions play the main role in the binding of indirubin to BSA. Furthermore, the displacement experiment shows that indirubin can bind to the subdomain IIA and the distance between the tryptophan residues in BSA and indirubin bound to site I was estimated to be 2.24 nm according to Föster's equation on the basis of fluorescence energy transfer.
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http://dx.doi.org/10.1248/cpb.54.1239DOI Listing
September 2006

Study of the interaction of artemisinin with bovine serum albumin.

Int J Biol Macromol 2006 Nov 2;39(4-5):291-7. Epub 2006 May 2.

College of Chemistry and Chemical Engineering, Guangxi Normal University, Guilin, Guangxi, PR China.

The study on the interaction of artemisinin with bovine serum albumin (BSA) has been undertaken at three temperatures, 289, 296 and 303 K and investigated the effect of common ions and UV C (253.7 nm) irradiation on the binding of artemisinin with BSA. The binding mode, the binding constant and the protein structure changes in the presence of artemisinin in aqueous solution at pH 7.40 have been evaluated using fluorescence, UV-vis and Fourier transform infrared (FT-IR) spectroscopy. The quenching constant K(q), K(sv) and the association constant K were calculated according to Stern-Volmer equation based on the quenching of the fluorescence of BSA. The thermodynamic parameters, the enthalpy (DeltaH) and the entropy change (DeltaS) were estimated to be -3.625 kJ mol(-1) and 107.419 J mol(-1)K(-1) using the van't Hoff equation. The displacement experiment shows that artemisinin can bind to the subdomain IIA. The distance between the tryptophan residues in BSA and artemisinin bound to site I was estimated to be 2.22 nm using Föster's equation on the basis of fluorescence energy transfer. The decreased binding constant in the presence of enough common ions and UV C exposure, indicates that common ions and UV C irradiation have effect on artemisinin binding to BSA.
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http://dx.doi.org/10.1016/j.ijbiomac.2006.04.008DOI Listing
November 2006