Publications by authors named "Jia-Jie Chen"

36 Publications

C-reactive protein/abumin ratio is a useful biomarker for predicting the mucosal healing in the Crohn disease: A retrospective study.

Medicine (Baltimore) 2021 Mar;100(10):e24925

Department of Gastroenterology, Huashan Hospital North, Fudan University.

Abstract: Ileocolonoscopy is currently recognized as the gold standard for evaluating mucosal healing in patients with Crohn disease (CD). However, the ideal noninvasive marker to assess mucosal healing instead of invasive ileocolonoscopy is not available. This study aimed to determine the correlations between the mucosal healing and serological optimizing markers in CD.This retrospective study consecutively included 62 CD patients with 137 hospitalizations between March 2014 and March 2020. On the basis of the Simple Endoscopic Score for Crohn's disease (SES-CD), the CD patients were divided into mucosal healing group (SES-CD ≤ 2) and nonmucosal healing group (SES-CD > 2). We collected the results of ileocolonoscopy examination and inflammatory markers and then serological optimizing markers, including C-reactive protein/albumin ratio (CRP/ALB), platelet/albumin ratio (PLT/ALB), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. The control group consisted of 50 healthy volunteers in the corresponding period.We found that CRP/ALB, PLT/ALB, NLR, and PLR were correlated with the mucosal healing of CD, and the correlation of CRP/ALB with the mucosal healing was the highest (r = -0.64). Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of CRP/ALB (0.87) was higher than NLR (0.69), PLR (0.72), and PLT/ALB (0.81). In the efficacy of assessing the mucosal healing in CD, the sensitivity of CRP/ALB, NLR, PLR, and PLT/ALB were 91.1%, 83.9%, 73.2%, and 73.2%, respectively, and the specificity was 76.5%, 46.9%, 64.2%, and 75.3%, respectively.CRP/ALB was the most appropriate marker to assess CD mucosal healing among the serological optimizing markers.
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http://dx.doi.org/10.1097/MD.0000000000024925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969241PMC
March 2021

Interleukin-6 signaling blockade treatment for cytokine release syndrome in COVID-19 (Review).

Exp Ther Med 2021 Jan 9;21(1):24. Epub 2020 Nov 9.

Department of Biochemistry and Molecular Biology, Health Science Center of Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.

A severe immune response in patients with coronavirus disease 2019 (COVID-19) can cause a potentially lethal unconstrained inflammatory cytokine storm, known as cytokine release syndrome (CRS). The present study provides an overview of the biology underlying CRS and how targeted inhibition of interleukin (IL)-6 signaling may improve outcomes and the survival of patients suffering from COVID-19. Preliminary clinical results have indicated that antagonism of the IL-6 receptor (IL-6R), including with the FDA-approved humanized monoclonal antibody tocilizumab, can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile. The available clinical data support the expansion of clinical trials using IL-6R targeting inhibitors for severe and critical COVID-19 treatment.
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http://dx.doi.org/10.3892/etm.2020.9456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690237PMC
January 2021

Ribonuclease T2 from Aspergillus fumigatus promotes T helper type 2 responses through M2 polarization of macrophages.

Int J Mol Med 2020 Aug 21;46(2):718-728. Epub 2020 May 21.

Department of Biochemistry and Molecular Biology, Health Science Center of Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic immunological response to Aspergillus fumigatus (Af) exposure, which induces a strong T helper 2 (Th2) response via mechanisms that have yet to be elucidated. The aim of the present study was to investigate the hypothesis that T2 ribonuclease from Af (Af RNASET2) induces M2‑type macrophage polarization to produce a T helper 2 (Th2) immune response. Recombinant Af RNASET2 (rAf RNASET2) was expressed and purified in a prokaryotic pET system and BALB/c mice were immunized with rAf RNASET2 for in vivo analyses. Expression levels of M2 polarization factors were evaluated in RAW264.7 macrophages treated with rAf RNASET2 in vitro using flow cytometry, reverse transcription‑quantitative PCR, and western blot analysis. The results predicted that the mature Af RNASET2 protein (382 amino acids; GenBank no. MN593022) contained two conserved amino acid sequence (CAS) domains, termed CAS‑1 and CAS‑2, which are also characteristic of the RNASET2 family proteins. The protein expression levels of the Th2‑related cytokines interleukin (IL)‑4, IL‑10, and IL‑13 were upregulated in mice immunized with rAf RNASET2. RAW264.7 macrophages treated with rAf RNASET2 showed increased mRNA expression levels of M2 factors [arginase 1, Il‑10, and Il‑13]; however, there was no difference in cells treated with rAf RNASET2 that had been inactivated with a ribonuclease inhibitor (RNasin). The protein expression levels of IL‑10 in macrophage culture supernatant were also increased following stimulation with rAf RNASET2. In addition, rAf RNASET2 upregulated the expression of phosphorylated mitogen activated protein kinases (MAPKs) in RAW264.7 cells, whereas MAPK inhibitors attenuated rAf RNASET2‑induced IL‑10 expression in RAW264.7 cells. In conclusion, the present study reveals that high rAf RNASET2 activity is required for rAf RNASET2‑induced M2 polarization of macrophages and suggests an important immune regulatory role for Af RNASET2 in ABPA pathogenesis.
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http://dx.doi.org/10.3892/ijmm.2020.4613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307867PMC
August 2020

The antipsychotic drug pimozide inhibits IgE-mediated mast cell degranulation and migration.

Int Immunopharmacol 2020 Jul 17;84:106500. Epub 2020 Apr 17.

Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China. Electronic address:

Background: Mast cells (MCs) mediate a key role in allergic diseases. Detailed studies of how the neuroleptic drug pimozide affects MC activity are lacking. The aim of this study was to investigate pimozide inhibition of immunoglobulin E (IgE)-mediated MC activation and MC-mediated allergic responses.

Method: MCs were stimulated with anti-dinitrophenyl (DNP) IgE antibodies and DNP-horse serum albumin (HSA) antigen (Ag), and anti-allergic pimozide effects were detected by measuring β-hexosaminidase levels. Morphological changes were observed histologically. In vivo pimozide effects were assessed in passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-sensitized active systemic anaphylaxis mouse (ASA) model experiments. Levels of phosphorylated (p-) SYK (spleen tyrosine kinase) and MAPKs (mitogen-activated protein kinases) were detected in western blots.

Results: We found that pimozide inhibited MC degranulation, reduced MC release of β-hexosaminidase dose-dependently in activated RBL-2H3 (IC: 13.52 μM) and bone marrow derived MC (BMMC) (IC: 42.42 μM), and reduced MC morphological changes. The IgE/Ag-induced migration effect was suppressed by pimozide treatment dose-dependently. Pimozide down-regulated IgE/Ag-induced phosphorylation of SYK and MAPKs in activated MCs. Moreover, pimozide attenuated allergic reactions in PCA and ASA model mice, and decreased MC populations among splenic cells.

Conclusions: The antipsychotic drug pimozide can suppress IgE-mediated MC activation in vitro and in vivo and should be considered for repurposing to suppress MC-mediated diseases.
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http://dx.doi.org/10.1016/j.intimp.2020.106500DOI Listing
July 2020

Aurora kinase inhibitor tozasertib suppresses mast cell activation in vitro and in vivo.

Br J Pharmacol 2020 06 6;177(12):2848-2859. Epub 2020 Apr 6.

Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen, China.

Background And Purpose: Mast cells are important in allergic reactions. Here, we assessed the anti-allergic effects of the anti-cancer drug tozasertib specifically regarding regulatory effects on mast cell activation.

Experimental Approach: Tozasertib effects on mast cell degranulation were determined by measuring β-hexosaminidase and histamine release and by assessing morphological changes in RBL-2H3 and mouse bone marrow-derived mast cells (BMMCs) stimulated with mouse anti-dinitrophenyl (DNP)-IgE/DNP-human serum albumin or human LAD2 cells activated with phorbol-12-myristate 13-acetate plus calcium ionophore (PMACI). Western blots were performed to detect the expression of molecules involved in NF-κB, MAPK, and Aurora kinase signalling. in vivo anti-allergic effects of tozasertib were determined in the murine IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) models.

Key Results: Tozasertib treatment decreased high-affinity IgE receptor (FcεRI) or PMACI-mediated degranulation in RBL-2H3 cells and in BMMCs or LAD2 cells as shown by β-hexosaminidase or histamine levels. Similarly, tozasertib prevented morphological changes in mast cells, such as particle release and F-actin reorganization. In addition, tozasertib markedly decreased expression of phosphorylated (p)-NF-κB p65, p-Erk1/2, p-p38, and p-Aurora A/B, indicating that tozasertib can inhibit the signalling pathway mediating mast cell activation. Tozasertib attenuated IgE/Ag-induced PCA dose-dependently, as shown by reduced Evans blue staining. Similarly, tozasertib reduced body temperature levels and serum histamine levels in OVA-challenged ASA mice.

Conclusion And Implications: The Aurora kinase inhibitor tozasertib suppressed mast cell activation in vitro and in vivo. Tozasertib may be a potential drug, targeting mast cell activation, to treat allergic diseases or mastocytosis.
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http://dx.doi.org/10.1111/bph.15012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236079PMC
June 2020

Solo Smart Fluorogenic Probe for Potential Cancer Diagnosis and Tracking in Vivo Tumorous Lymphatic Systems via Distinct Emission Signals.

Anal Chem 2020 01 9;92(1):1541-1548. Epub 2019 Dec 9.

Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, Center for Biomedical Photonics, College of Physics and Optoelectronic Engineering , Shenzhen University , Shenzhen 518060 , China.

A versatile twisted-intramolecular-charge-transfer (TICT)-based near-infrared (NIR) fluorescent probe () has been judiciously designed and synthesized that could be utilized for potential cancer diagnosis and to track lymph node(s) in mice through distinct emission signals. Essentially, the probe rendered the capability to preferentially recognize the cancer cells over the noncancer cells by polarity-guided lipid droplet specific differential bioimaging (in green emission channel) studies. The probe also exhibited selective turn-on fluorescence response toward HSA/BSA in physiological media (aqueous PBS buffer; pH 7.4) at far-red/NIR regions, because of the 1:1 chelation between the probe and HSA/BSA. Therefore, the fluorescent probe was then maneuvered to track the draining lymphatic system and sentinel lymph node in tumor mice model by fluorescence imaging (NIR/deep-red channel), wherein the accumulated albumin protein in the draining tumor lymphatic system facilitated the in situ formation of the fluorescent albumin- complex.
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http://dx.doi.org/10.1021/acs.analchem.9b04834DOI Listing
January 2020

Increased expression of hematological and neurological expressed 1 (HN1) is associated with a poor prognosis of hepatocellular carcinoma and its knockdown inhibits cell growth and migration partly by down-regulation of c-Met.

Kaohsiung J Med Sci 2020 Mar 20;36(3):196-205. Epub 2019 Nov 20.

Department of Gastroenterology, Huashan Hospital North, Fudan University, Shanghai, China.

Hematologic and neurological expression 1 (HN1) has been reported to involved in certain cancers, but its role in hepatocellular carcinoma (HCC) is largely unknown. The contribution of HN1 to HCC progression was investigated in the present study. We found that HN1 was significantly up-regulated in HCC tissues, compared with normal tissues, by analyzing the Oncomine and Human Protein Atlas database; and found that high expression of HN1 was markedly associated with worse overall survival, relapse-free survival, progression- free survival and disease-specific survival in HCC patients via exploring the Kaplan-Meier plotter database. Functional assays revealed that HN1 knockdown by siRNA induced G1 cell cycle arrest, and inhibited the growth and migration of HCC cells; accordingly, HN1 over-expression promoted HCC cells proliferation and migration. Further studies indicated that HN1 knockdown reduced the expression of cyclin D1 and CDK4, while upregulated the cell cycle inhibitor p21WAF1/Cip1. Moreover, HN1 knockdown decreased c-Met (receptor tyrosine kinase of hepatocyte growth factor) expression, and suppressed ERK activation, which is a common downstream signaling pathway triggered by c-Met; consistently, HN1 over-expression reversed these effects. Meanwhile, down-regulation of c-Met partly eliminated the effect of HN1 over-expression in HCC cells. Thus, the present findings suggested that HN1 promotes the progression of HCC to some extent by up-regulating the expression of c-Met, and may act as a potential biomarker and therapeutic target for the treatment of HCC.
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http://dx.doi.org/10.1002/kjm2.12156DOI Listing
March 2020

Identification of immunodominant IgE epitopes of the major house dust mite allergen Der f 24.

Int J Mol Med 2019 Nov 18;44(5):1888-1898. Epub 2019 Sep 18.

Department of Biochemistry and Molecular Biology, Health Science Center of Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.

Previously, a ubiquinol‑cytochrome c reductase binding protein (UQCRB) homolog was identified in the house dust mite (HDM) species Dermatophagoides farinae (Der f) as a major allergen. In the present study, the immunodominant immunoglobulin E (IgE) epitope of the protein Der f 24 was investigated. Analysis of the homologous amino acid (aa) sequences in Der f and human UQCRB was performed. Four different recombinant Der f 24 and hybrid proteins formed by integrating Der f and human UQCRB sequences were expressed in Escherichia coli, purified using Ni‑NTA resins, and IgE‑binding activity was determined using IgE‑western blotting and enzyme‑linked immunosorbent assay (ELISA) experiments. IgE epitopes were further identified by IgE‑dot blotting and IgE‑ELISA with synthetic polypeptides and HDM‑allergic sera. Three‑dimensional (3D) structural modeling was used to analyze the position of the immunodominant IgE epitope. The amino acid sequence homology between Der f 24 and the human UQCRB protein was determined to be 39.34%. IgE‑ELISA and western blot analysis showed that all of the Der f‑human UQCRB hybrid proteins generated, except for the one lacking 59 residues of the N‑terminal region of Der f 24, were bound by allergic serum IgE. A synthetic polypeptide consisting of 32 residues of the N‑terminal reacted with IgEs from HDM‑allergic sera and could be used to generate high titer specific IgG or specific IgE antibodies in immunized mice. The 32‑aa N‑terminal region of Der f 24 was localized to a structural protrusion, which may facilitate specific IgE‑binding. These results indicate that the immunodominant IgE epitope of Der f 24 is located mainly in a 32‑residue region of the N‑terminus. These findings may inform the mechanisms of HDM allergy sensitization and allergy immunotherapy development.
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http://dx.doi.org/10.3892/ijmm.2019.4345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777665PMC
November 2019

CDK4/6 inhibitor palbociclib suppresses IgE-mediated mast cell activation.

J Transl Med 2019 08 20;17(1):276. Epub 2019 Aug 20.

Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen, 518060, People's Republic of China.

Background: Mast cell activation causes degranulation and release of cytokines, thereby promoting inflammation. The aim of this study was to investigate the inhibitory effect of CDK4/6 inhibition on mast cell activation in vitro and in vivo.

Methods: RBL-2H3 rat basophilic leukemia cells (BLCs) and mouse bone marrow-derived mast cells (BMMCs) were sensitized with anti-dinitrophenol (DNP) immunoglobulin (Ig)E antibodies, stimulated with DNP-human serum albumin (HSA) antigens, and treated with the CDK4/6 inhibitor palbociclib. Histological stains were applied to reveal cytomorphological changes. Murine IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) models were used to examine palbociclib effects on allergic reactions in vivo. Western blots were performed to detect the expression of cell signaling molecules associated with mast cell activation.

Results: Activated BLCs and BMMCs released copious granule-related mediators (histamine and β-hexosaminidase), which was reduced by palbociclib in a concentration-dependent manner. Palbociclib inhibited expression of the mast cell activation marker CD63 in activated BLCs and inhibited granule release (visualized with toluidine blue staining) while preventing morphological changes, (elongated shape maintained) and filamentous actin (F-actin) reorganization. Palbociclib suppressed molecular Lyn and/or mitogen-activated protein kinase (MAPK) signaling associated with mast cell activation in stimulated BLCs and attenuated allergic reactions in PCA mice dose dependently. Palbociclib attenuated body temperature reduction and diminished serum histamine levels in ovalbumin OVA-challenged ASA mice.

Conclusion: Palbociclib suppresses IgE-mediated mast cell activation in vitro and in vivo, suggesting that it may be developed into a therapy for mast cell-mediated allergic diseases via inhibition of mast cell degranulation.
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http://dx.doi.org/10.1186/s12967-019-2026-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702723PMC
August 2019

Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer.

Oncol Rep 2019 Sep 11;42(3):1101-1109. Epub 2019 Jul 11.

Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China.

The antipsychotic drug pimozide has been found to exhibit anticancer effects. Previously, it was demonstrated that pimozide inhibits hepatocellular carcinoma (HCC) cell growth, but its pharmacodynamic characteristics remain unclear. The aim of the present study was to investigate the reversibility and mechanism of the ability of pimozide to inhibit cell proliferation in liver cancer. Cell viability was determined by Cell Counting Kit‑8 and colony formation assay. The cell cycle distribution was analyzed by flow cytometry with Ki‑67 and PI staining. ROS production of HCC cells was detected with DCFH‑DA and inhibited with NAC treatment. Western blot assay was performed to detect the expression of related signaling molecules in HCC cells. Our results showed that pimozide promoted G0/G1 phase arrest in HCC cell lines without significant cell death. Its anti‑proliferative effects on HCC cells were reversible, consistent with involvement of cell quiescence and reactive oxygen species (ROS) production. Pimozide enhanced inhibition of HCC cell proliferation by sorafenib. In conclusion, elucidation of pimozide's reversible proliferation inhibition in liver cancer and additive activity with a well‑established anticancer drug warrants further exploration of the potential of pimozide as an adjuvant anticancer therapy.
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http://dx.doi.org/10.3892/or.2019.7229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667923PMC
September 2019

Identification of immunodominant IgE binding epitopes of Der p 24, a major allergen of .

Clin Transl Allergy 2019 23;9:28. Epub 2019 May 23.

1Department of Biochemistry and Molecular Biology, Health Science Center of Shenzhen University, Shenzhen, China.

Background: The identification of house dust mite (HDM) allergens and epitopes is important for allergy diagnosis and treatment. We sought to identify the group 24 allergen (Der p 24) and to identify its immunodominant IgE epitope(s).

Methods: Der p 24 cDNA was cloned and expressed in a pET expression system. The IgE binding activity of purified recombinant (r)Der p 24 was evaluated by western blotting. Truncated Der p 24 proteins and overlapping synthetic polypeptides were subjected to IgE binding assays. Balb/c mice were immunized to investigate IgE epitope induction of IgE production. IgE binding of the 32 N-terminal residues of Der p 24 was compared to other Der p epitopes in enzyme-linked immunosorbent assays and dot blot assays. Human skin prick tests (SPTs) were performed.

Results: We cloned and expressed Der p 24 cDNA (GenBank accession no. KP893174.1). HDM allergic sera bound rDer p 24 in vitro and 5/10 HDM allergic patients (50%) had positive SPT reactions to rDer p 24. The immunodominant IgE epitope of Der p 24 was localized to the N-terminal 32-residue region, which produced a high specific IgE antibody titer in vivo and promoted mast cell β-hexosaminidase release. The IgE binding activity this N-terminal epitope of Der p 24 was stronger than that of Der p 1 or Der p 2 IgE epitopes.

Conclusions: We identified Der p 24 as a major HDM allergen with strong IgE binding activity via an immunodominant IgE epitope in the N-terminal 32-residue region, which triggers IgE production in vivo. The identified Der p 24 epitope may support HDM allergy diagnosis and treatment.
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http://dx.doi.org/10.1186/s13601-019-0266-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533760PMC
May 2019

Verteporfin blocks Clusterin which is required for survival of gastric cancer stem cell by modulating HSP90 function.

Int J Biol Sci 2019 1;15(2):312-324. Epub 2019 Jan 1.

School of Medicine, Shenzhen University, Shenzhen 518055, China.

Gastric cancer stem cell (GCSC) is implicated in gastric cancer relapse, metastasis and drug resistance. However, the key molecule(s) involved in GCSC survival and the targeting drugs are poorly understood. We discovered increased secreted clusterin (S-Clu) protein expression during the sphere-forming growth of GCSC via mass spectrometry. Overexpression of clusterin was detected in 69/90 (77%) of primary GC tissues and significantly associated with T stage, lymph node metastasis and TNM stage. Depletion of clusterin (Clu, the full-length intracellular clusterin) led to the declustering of GCSC tumorspheres and apoptosis of GCSC. Subsequently, we found clusterin was in complex with heat shock protein 90 beta (HSP90) and involved in regulating the cellular level of HSP90 client proteins. Furthermore, by screening a collection of drugs/inhibitors, we found that verteporfin (VP), a phototherapy drug, blocked clusterin gene expression, decreased the HSP90 client proteins and caused cell death of GCSC. VP treatment is more effective in eradicating GCSCs than in killing GC cells. Both clusterin silencing or VP treatment deterred tumor growth in human GCSC xenografts. These findings collectively suggest that GC patients can promptly benefit from clusterin-targeted therapy as well as VP treatment in combination with or subsequent to conventional chemotherapy for reducing mortality of GC.
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http://dx.doi.org/10.7150/ijbs.29135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367548PMC
January 2020

Longitudinal behavioral and fMRI-based assessment of inhibitory control in heroin addicts on methadone maintenance treatment.

Exp Ther Med 2018 Oct 3;16(4):3202-3210. Epub 2018 Aug 3.

Department of Radiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.

The objective of the present study was to determine whether methadone maintenance treatment (MMT) in heroin-dependent patients affects inhibitory control, whether any MMT-induced changes correlate with methadone dose and MMT duration, and whether these changes depend on the psychological characteristics of patients, such as depression, anxiety and impulsivity. Response inhibition in the GO/NO-GO test was combined with functional magnetic resonance imaging (fMRI) scanning data to examine whether MMT affects inhibitory control in 21 heroin-addicted patients who had already undergone at least three months of MMT. Patients were evaluated one year prior to and after the MMT period. Participants exhibited no difference in their GO/NO-GO reaction time and accuracy rate, or in their false alarm rate under NO-GO conditions. However, increased activation was detected in numerous brain regions in their 12-month fMRI scans, although these were not in the frontal-striatal loop. Increased fMRI activation in the left precentral gyrus and superior temporal gyrus were negatively correlated with the daily methadone dose and total methadone dose during the one-year study period. In conclusion, these results suggested that MMT over one year does not significantly change the behavioral indicators of inhibitory control function in heroin-dependent patients. The increase in activation leads to the hypothesis that MMT over one year may increase cognitive inhibitory control, which may be the result of the combined negative effect of methadone and the positive effect of functional recovery after withdrawal of heroin.
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http://dx.doi.org/10.3892/etm.2018.6571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125843PMC
October 2018

Identification and characterization of new Muscodor endophytes from gramineous plants in Xishuangbanna, China.

Microbiologyopen 2019 04 21;8(4):e00666. Epub 2018 Jun 21.

State Key Laboratory for Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

The endophytic fungi Muscodor spp. produce volatile organic compounds (VOCs) which can inhibit and even kill pathogenic fungi, bacteria, and nematodes. Nine endophytic fungal strains, isolated from the shoots of gramineous plants including Arthraxon hispidus, Eleusine indica, Oplismenus undulatifolius, and Oryza granulata, were identified as Muscodor through phylogenetic analysis of the internal transcribed spacer. Through an SPSS K-means cluster analysis, the nine Muscodor strains were divided into four groups based on the antifungal activities of the VOCs produced by these fungi determined by a two-section confrontation test. The first group contains the strains Y-L-54, W-S-41, Y-S-35, W-T-27, and Y-L-56, which showed the strongest activity. The second and third groups contain W-S-35 and Y-L-43, which showed stronger and moderate activity, respectively. The fourth group contains W-S-38 and N-L-7, which were the weakest in inhibiting the tested pathogens. Thirty-five compounds and the relative amounts of VOCs were determined by SPME-GC-MS and comparison with the NIST14 mass spectrometry database and Agilent MassHunter qualitative and quantitative analyses. These 35 compounds were classified into two different categories: (a) the product of fatty acid degradation, and (b) the intermediate and final metabolite of the metabolic pathway with the precursor of mevalonic acid. SPSS clustering analysis showed that the chemical components of VOCs might be correlated with their bioactivity rather than their phylogenetic assignment and some of the identified compounds might be responsible for antifungal activity. In conclusion, new Muscodor endophytes were recorded in tropical gramineous plants and a number of strains showed remarkable bioactive properties. Therefore, they have important potential applications in the fields of plant disease control.
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http://dx.doi.org/10.1002/mbo3.666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460276PMC
April 2019

Murine Model of Leukemia Cell-Induced Spinal Bone Destruction.

Biomed Res Int 2017 28;2017:3521481. Epub 2017 Sep 28.

Institute of Molecular Medicine, Health Science Center, Shenzhen University, Shenzhen 518060, China.

Osteolytic bone lesions can be a consequence of leukemic bone infiltration or focal bone destruction by inflammatory factors released from leukemic cells. Destructive bone lesions have a negative impact on the quality of life of leukemia patients, causing unbearable pain and, in some cases, limb paralysis. However, the mechanism, by which leukemic cells produce destructive bone lesions, and the effect of therapeutics on osteolytic lesions have not been fully elucidated yet and, thus, stand to benefit from an model. To that end, HL-60 cells were transformed by retrovirus-mediated constitutively active (CA) STAT5 expression and injected into nonobese diabetic (NOD)/SCID mice via the tail vein. After three weeks, lumbar spines were subjected to histocytometric analysis. Xenograft mice developed hind limb paralysis in 2-3 weeks, which was consistent with the consequences of spinal bone destruction by extramedullary invasion of leukemia cells. The model will improve the understanding and treatment of osteolytic bone lesions caused by myeloid leukemic cells.
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http://dx.doi.org/10.1155/2017/3521481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637823PMC
August 2018

Chlamydia trachomatis, Ureaplasma urealyticum and Neisseria gonorrhoeae among Chinese women with urinary tract infections in Shanghai: A community-based cross-sectional study.

J Obstet Gynaecol Res 2018 Mar 22;44(3):495-502. Epub 2017 Dec 22.

Clinical Laboratory, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Aim: This study explored chlamydia trachomatis (CT), ureaplasma urealyticum (UU) and/or neisseria gonorrhoeae (NG) in 5893 women with urinary tract infections (UTIs) in Shanghai.

Methods: From January 2009 to December 2014, 5893 women with UTIs in Shanghai were selected to undergo CT, UU and NG detection. Baseline characteristics including age, education level, occupation, reproductive history, sexual behavior and contraceptive method were obtained for epidemiological analysis.

Results: The total CT, UU and/or NG infection rate in the urine samples of 5893 patients was 50.69% (2987/5893), while the infection rate in vaginal secretion samples was 56.22% (3313/5893). The two detection methods were consistent. Patients aged 21-30, service personnel and unemployed persons had the highest rates of CT, UU and/or NG infection, while patients with higher education levels exhibited lower rates. As the number of previous pregnancies, natural births, abortions, sexual partners and the frequency of sexual intercourse increased, the rates of CT, UU and/or NG infection were elevated. Sexual intercourse during the menstruation period, a lack of cleaning before sexual intercourse and the use of intrauterine devices could all lead to an increased rate of CT, UU and/or NG infection.

Conclusions: These data revealed that the rate of CT, UU and/or NG infection may be associated with age, education level, occupation, reproductive history, sexual behavior and type of contraceptive method in female patients with UTI in Shanghai.
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http://dx.doi.org/10.1111/jog.13526DOI Listing
March 2018

The STAT3 inhibitor pimozide impedes cell proliferation and induces ROS generation in human osteosarcoma by suppressing catalase expression.

Am J Transl Res 2017 15;9(8):3853-3866. Epub 2017 Aug 15.

School of Medicine, Shenzhen UniversityShenzhen 518060, People's Republic of China.

Currently, there is a considerable need to develop new treatments for osteosarcoma (OS), a very aggressive bone cancer. The activation of STAT3 signaling is positively associated with poor prognosis and aggressive progression in OS patients. Our previous study reported that the FDA-approved antipsychotic drug pimozide had anti-tumor activity against hepatocellular carcinoma and prostate cancer cells by suppressing STAT3 activity. Therefore, the aim of this study was to investigate the specific effect of pimozide on OS cells and the underlying molecular mechanism. Pimozide inhibited cell proliferation, colony formation, and sphere formation capacities of the OS cells in a dose-dependent manner, inducing G0/G1 phase cell cycle arrest. Pimozide reduced the percentage of side population cells representing cancer stem-like cells and enhanced the sensitivity of OS cells to 5-FU induced proliferative inhibition. In addition, pimozide induced apoptosis of U2OS cells, which showed increased expression of cleaved-PARP, a marker of programmed cell death. Moreover, pimozide suppressed Erk signaling in OS cells. Importantly, pimozide induced ROS generation by downregulating the expression of the antioxidant enzyme catalase (CAT). NAC treatment partially reversed the ROS generation and cytotoxic effects induced by pimozide. CAT treatment attenuated the pimozide-induced proliferation inhibition. The decrease of CAT expression induced by pimozide was potentially mediated through the suppression of cellular STAT3 activity in OS cells. Thus, pimozide may be a novel STAT3 inhibitor that suppresses cellular STAT3 activity to inhibit OS cells or stem-like cells and is a novel potential anti-cancer agent in OS treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575198PMC
August 2017

A Novel Derivative of (-)mycousnine Produced by the Endophytic Fungus , Exhibits High and Selective Immunosuppressive Activity on T Cells.

Front Microbiol 2017 5;8:1251. Epub 2017 Jul 5.

Institute of Materia Medica, Zhejiang Academy of Medical SciencesHangzhou, China.

An endophytic fungus, ZJLQ129, was isolated from the leaves of the traditional Chinese medicine Smilax china. From the fermentation broth and mycelium, a dibenzofurane compound (-)mycousnine (1) was isolated. Chemical modification of it to the amide derivative (-)mycousnine enamine (2), which is new to science, was found to have high and selective immunosuppressive activity: similar to cyclosporin A, (-)mycousnine enamine (2) selectively inhibited T cell proliferation, suppressed the expression of the surface activation antigens CD25 and CD69 and the formation and expression of the cytokines interleukin-2 as well as interferon γ in activated T cells, but did not show any effect on the proliferation of B cells and cancer cells (PANC-1 and A549) and the activation of macrophages. Furthermore, the cytotoxicity of (-)mycousnine enamine was lower than that of cyclosporin A, and its therapeutic index (TC50/EC50) was 4,463.5, which is five-fold higher than that of cyclosporin A. We conclude that (-)mycousnine enamine (2), the semi-synthestic product prepared from the native product (-)mycousnine (1) of the endophyte M. nawae is a novel effective immunosuppressant showing low toxicity and high selectivity.
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http://dx.doi.org/10.3389/fmicb.2017.01251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496962PMC
July 2017

Aurora A Kinase Inhibitor AKI603 Induces Cellular Senescence in Chronic Myeloid Leukemia Cells Harboring T315I Mutation.

Sci Rep 2016 11 8;6:35533. Epub 2016 Nov 8.

Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China; Institute of Hematology, Sun Yat-sen University, Guangzhou 510630, China.

The emergence of resistance to imatinib mediated by mutations in the BCR-ABL has become a major challenge in the treatment of chronic myeloid leukemia (CML). Alternative therapeutic strategies to override imatinib-resistant CML are urgently needed. In this study, we investigated the effect of AKI603, a novel small molecule inhibitor of Aurora kinase A (AurA) to overcome resistance mediated by BCR-ABL-T315I mutation. Our results showed that AKI603 exhibited strong anti-proliferative activity in leukemic cells. AKI603 inhibited cell proliferation and colony formation capacities in imatinib-resistant CML cells by inducing cell cycle arrest with polyploidy accumulation. Surprisingly, inhibition of AurA by AKI603 induced leukemia cell senescence in both BCR-ABL wild type and T315I mutation cells. Furthermore, the induction of senescence was associated with enhancing reactive oxygen species (ROS) level. Moreover, the anti-tumor effect of AKI603 was proved in the BALB/c nude mice KBM5-T315I xenograft model. Taken together, our data demonstrate that the small molecule AurA inhibitor AKI603 may be used to overcome drug resistance induced by BCR-ABL-T315I mutation in CML.
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http://dx.doi.org/10.1038/srep35533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099696PMC
November 2016

[Zooplankton community structure in relation to influencing factors in different parts of Hangzhou Bay in autumn].

Ying Yong Sheng Tai Xue Bao 2015 Sep;26(9):2859-66

Based on the data collected from three oceanographic surveys in the east area of north (30.68°-30.83° N,121.67°-121.87° E), the east area of south (29.95°-30.24° N,121.60°- 121.85° E), and the west area of north (30.58°--30.77° N,121.31°--121.56° E) Hangzhou Bay during the autumn of 2009, 2011 and 2012, we analyzed the species composition, ecological groups and the similarity of zooplankton community, as well as influencing factors. The results indicated that a total of 14 species belonging to 6 groups were identified in the west area of north Hangzhou Bay. Tortanus vermiculus was the predominant species. The zooplankton assembles were mainly influenced by the runoff strength of the Qiantang River. The zooplankton fauna was mainly composed of the subtropical estuarine brackish-water species, accounting for 79.8% in the total abundance. A total of 19 species belonging to 6 groups were identified in the east area of north Hangzhou Bay. The composition of zooplankton community was mainly influenced by the Changjiang diluted water and offshore water of the East China Sea. It was mainly composed of warm-temperature and subtropical nearshore low-salinity species, accounting for 43.5% and 31.1% in the total abundance, respectively. In the east area of south Hangzhou Bay, a total of 25 species belonging to 7 groups were identified. The composition of zooplankton community was mainly influenced by the offshore water of the East China Sea. The dominate eco-group types were subtropical nearshore low-salinity and subtropical nearshore species, accounting for 72.3% and 18.3% in the total abundance, respectively. And the ecological groups of species with the highest abundance was Labidocera sinilobata, accounting for 65.3% in the total abundance. By hierarchical cluster analysis and non-metric multidimensional scaling (NMDS) method, it was found that the zooplankton communities in the three parts of Hangzhou Bay were significantly different, which were closely associated with the impacts of different water masses from these parts.
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September 2015

The antipsychotic drug pimozide inhibits cell growth in prostate cancer through suppression of STAT3 activation.

Int J Oncol 2016 Jan 4;48(1):322-8. Epub 2015 Nov 4.

Vaccine Research Institute of Sun Yat-sen University, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, P.R. China.

Currently, drug discovery and development for clinical treatment of prostate cancer has received increased attention, specifically the STAT3 inhibitor. Our previous study reported that the neuroleptic drug pimozide had antitumor activity against hepatocellular carcinoma cells or stem-like cells through suppressing the STAT3 activity. In the present study we demonstrate that pimozide inhibits cell growth and cellular STAT3 activation in prostate cancer cells. Our results showed that pimozide inhibited prostate cancer cell proliferation in a dose- and time-dependent manner by inducing G1 phase cell cycle arrest, downregulated the ability of colony formation and sphere forming, as well as suppressed cells migration in both DU145 and LNCaP cells. Surprisingly, pimozide reduced the basal expression of phosphorylation STAT3 at tyrosine 705 and reversed the expression of phosphorylation of STAT3 induced by IL-6 addition, suggesting that pimozide can suppress cellular STAT3 activation. Thus, the antipsychotic agent pimozide may be a potential and novel therapeutic for patients with advanced prostate cancer.
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http://dx.doi.org/10.3892/ijo.2015.3229DOI Listing
January 2016

The neuroleptic drug pimozide inhibits stem-like cell maintenance and tumorigenicity in hepatocellular carcinoma.

Oncotarget 2017 Mar;8(11):17593-17609

Organ Transplantation Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.

Drug repurposing is currently an important approach for accelerating drug discovery and development for clinical use. Hepatocellular carcinoma (HCC) presents drug resistance to chemotherapy, and the prognosis is poor due to the existence of liver cancer stem-like cells. In this study, we investigated the effect of the neuroleptic agent pimozide to inhibit stem-like cell maintenance and tumorigenicity in HCC. Our results showed that pimozide functioned as an anti-cancer drug in HCC cells or stem-like cells. Pimozide inhibited cell proliferation and sphere formation capacities in HCC cells by inducing G0/G1 phase cell cycle arrest, as well as inhibited HCC cell migration. Surprisingly, pimozide inhibited the maintenance and tumorigenicity of HCC stem-like cells, particularly the side population (SP) or CD133-positive cells, as evaluated by colony formation, sphere formation and transwell migration assays. Furthermore, pimozide was found to suppress STAT3 activity in HCC cells by attenuating STAT3-dependent luciferase activity and down-regulating the transcription levels of downstream genes of STAT3 signaling. Moreover, pimozide reversed the stem-like cell tumorigenic phenotypes induced by IL-6 treatment in HCC cells. Further, the antitumor effect of pimozide was also proved in the nude mice HCC xenograft model. In short, the anti-psychotic agent pimozide may act as a novel potential anti-tumor agent in treating advanced HCC.
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http://dx.doi.org/10.18632/oncotarget.4307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392272PMC
March 2017

A novel compound against oncogenic Aurora kinase A overcomes imatinib resistance in chronic myeloid leukemia cells.

Int J Oncol 2015 9;46(6):2488-96. Epub 2015 Apr 9.

Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Sun Yat-sen Institute of Hematology, Guangzhou 510630, P.R. China.

Drug resistance still represents a major obstacle to successful chronic myeloid leukemia (CML) treatment and novel compounds or strategies to override this challenging problem are urgently required. Here, we evaluated a novel compound AKI603 against oncogenic Aurora kinase A (Aur-A) in imatinib-resistant CML cells. We found that Aur-A was highly activated in imatinib-resistant KBM5-T315I cells. AKI603 significantly inhibited the phosphorylation of Aur-A kinase at Thr288, while had little inhibitory effect on BCR-ABL kinase in both KBM5 and KBM5-T315I cells. AKI603 inhibited cell viability, and induced cell cycle arrest with polyploidy accumulation in KBM5 and KBM5-T315I cells. Moreover, inhibition of Aur-A kinase by AKI603 suppressed colony formation capacity without promoting obvious apoptosis. Importantly, AKI603 promoted cell differentiation in both CML cell types. Thus, our study suggested the potential clinical use of small molecule Aurora kinase inhibitor AKI603 to overcome imatinib resistance in CML treatment.
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http://dx.doi.org/10.3892/ijo.2015.2960DOI Listing
January 2016

Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation.

PLoS One 2014 15;9(8):e105381. Epub 2014 Aug 15.

Department of Hematology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Sun Yat-sen Institute of Hematology, Sun Yat-sen University, Guangzhou, China.

Nowadays, drug resistance still represents a major obstacle to successful acute myeloid leukemia (AML) treatment and the underlying mechanism is not fully elucidated. Here, we found that high expression of c-Myc was one of the cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc over-expression in leukemic cells induced resistance to chemotherapeutic drugs, enhanced colony formation capacity and inhibited cell differentiation induced by all-trans retinoic acid (ATRA). Meanwhile, inhibition of c-Myc by shRNA or specific c-Myc inhibitor 10058-F4 rescued the sensitivity to cytotoxic drugs, restrained the colony formation ability and promoted differentiation. RT-PCR and western blotting analysis showed that down-regulation of C/EBPβ contributed to the poor differentiation state of leukemic cells induced by c-Myc over-expression. Importantly, over-expression of C/EBPβ could reverse c-Myc induced drug resistance. In primary AML cells, the c-Myc expression was negatively correlated with C/EBPβ. 10058-F4, displayed anti-proliferative activity and increased cellular differentiation with up-regulation of C/EBPβ in primary AML cells. Thus, our study indicated that c-Myc could be a novel target to overcome drug resistance, providing a new approach in AML therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0105381PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134294PMC
December 2015

Up-regulation of P21 inhibits TRAIL-mediated extrinsic apoptosis, contributing resistance to SAHA in acute myeloid leukemia cells.

Cell Physiol Biochem 2014 8;34(2):506-18. Epub 2014 Aug 8.

Department of Hematology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou; Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.

Background/aim: P21, a multifunctional cell cycle-regulatory molecule, regulates apoptotic cell death. In this study we examined the effect of altered p21 expression on the sensitivity of acute myeloid leukemia cells in response to HDAC inhibitor SAHA treatment and investigated the underlying mechanism.

Methods: Stably transfected HL60 cell lines were established in RPMI-1640 with supplementation of G-418. Cell viability was measured by MTT assay. Western blot was applied to assess the protein expression levels of target genes. Cell apoptosis was monitored by AnnexinV-PE/7AAD assay.

Results: We showed HL60 cells that that didn't up-regulate p21 expression were more sensitive to SAHA-mediated apoptosis than NB4 and U937 cells that had increased p21 level. Enforced expression of p21 in HL60 cells reduced sensitivity to SAHA and blocked TRAIL-mediated apoptosis. Conversely, p21 silencing in NB4 cells enhanced SAHA-mediated apoptosis and lethality. Finally, we found that combined treatment with SAHA and rapamycin down-regulated p21 and enhanced apoptosis in AML cells.

Conclusion: We conclude that up-regulated p21 expression mediates resistance to SAHA via inhibition of TRAIL apoptotic pathway. P21 may serve as a candidate biomarker to predict responsiveness or resistance to SAHA-based therapy in AML patients. In addition, rapamycin may be an effective agent to override p21-mediated resistance to SAHA in AML patients.
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http://dx.doi.org/10.1159/000363018DOI Listing
April 2015

Inhibition of mTOR pathway sensitizes acute myeloid leukemia cells to aurora inhibitors by suppression of glycolytic metabolism.

Mol Cancer Res 2013 Nov 5;11(11):1326-36. Epub 2013 Sep 5.

Department of Hematology, the Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, China.

Aurora kinases are overexpressed in large numbers of tumors and considered as potential therapeutic targets. In this study, we found that the Aurora kinases inhibitors MK-0457 (MK) and ZM447439 (ZM) induced polyploidization in acute myeloid leukemia (AML) cell lines. The level of glycolytic metabolism was significantly increased in the polyploidy cells, which were sensitive to glycolysis inhibitor 2-deoxy-D-glucose (2DG), suggesting that polyploidy cells might be eliminated by metabolism deprivation. Indeed, inhibition of mTOR pathway by mTOR inhibitors (rapamycin and PP242) or 2DG promoted not only apoptosis but also autophagy in the polyploidy cells induced by Aurora inhibitors. Mechanically, PP242 or2DGdecreased the level of glucose uptake and lactate production in polyploidy cells as well as the expression of p62/SQSTM1. Moreover, knockdown of p62/SQSTM1 sensitized cells to the Aurora inhibitor whereas overexpression of p62/SQSTM1 reduced drug efficacy. Thus, our results revealed that inhibition of mTOR pathway decreased the glycolytic metabolism of the polyploidy cells, and increased the efficacy of Aurora kinases inhibitors, providing a novel approach of combination treatment in AML.
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http://dx.doi.org/10.1158/1541-7786.MCR-13-0172DOI Listing
November 2013

Inhibition of autophagy augments the anticancer activity of α-mangostin in chronic myeloid leukemia cells.

Leuk Lymphoma 2014 Mar 18;55(3):628-38. Epub 2013 Jul 18.

Department of Hematology, Third Affiliated Hospital, Sun Yat-Sen University , Guangzhou , People's Republic of China.

Natural products possessing anticancer activity have been extensively studied because of their low toxicity and potential effect. α-Mangostin, a component of Garcinia mangostana Linn, is a xanthone derivative shown to have antioxidant and antitumor properties. This study was carried out to investigate how to improve the anticancer effects of α-mangostin in chronic myeloid leukemia (CML) cell lines bearing wild-type BCR-ABL or BCR-ABL-T315I mutation. We showed that α-mangostin inhibited cell proliferation of K562, KBM5 and KBM5-T315I cells in both a time- and dose-dependent manner. Significantly, α-mangostin increased the number of apoptotic cells and induced DNA fragmentation compared to control cells. Moreover, α-mangostin selectively inhibited proliferation in primary CML cells, while showing limited lethality in normal hematopoietic progenitors. Additionally, α-mangostin induced not only apoptosis but also autophagy in CML cells. α-Mangostin dramatically increased the expression levels of LC-3II, an autophagosome marker in mammals, and the accumulation of autophagic vacuoles (AVs). Inhibition of autophagy by chloroquine enhanced α-mangostin-mediated cytotoxicity through increasing apoptosis. Taken together, our data suggest that targeting the autophagy pathway is a promising therapeutic strategy to enhance α-mangostin-induced apoptosis. Our study provides an approach for future studies to explore this combination for the treatment of CML.
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http://dx.doi.org/10.3109/10428194.2013.802312DOI Listing
March 2014

[Efficacy and safety of telbivudine and adefovir dipivoxil for the treatment of chronic hepatitis B patients with high level hepatitis B virus load and hepatitis B e antigen-positivity].

Zhonghua Gan Zang Bing Za Zhi 2012 Nov;20(11):859-60

Infectitious Diseases Department, the First Affiliated Hospital of Soochow University, Suzhou, China.

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November 2012

Effect of recombinant Lactobacillus casei expressing interleukin-10 in dextran sulfate sodium-induced colitis mice.

J Dig Dis 2013 Feb;14(2):76-83

Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China.

Objective: To study the effect of recombinant Lactobacillus casei (L.casei) expressing interleukin (IL)-10 combined with 5-aminosalicylic acid (5-ASA) in dextran sulfate sodium (DSS)-induced colitis mice.

Methods: Recombinant L. casei CECT 5276, which can secrete IL-10, was constructed. The length of colon tissue, disease activity index (DAI) and histological score (HS) of the mice were determined to evaluate the modeling and the effectiveness of L. casei. Real-time polymerase chain reaction (PCR), Western blot and ELISA were used to determine the levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor (PPAR)-γ, interferon (IFN)-γ, transforming growth factor (TGF)-β and IL-10.

Results: Recombinant L. casei expressing IL-10 combined with 5-ASA was more effective than L. casei with 5-ASA. Among the three different concentrations of the recombinant L. casei, the highest concentration group (2 × 10(9) colony-forming units/mL) had the best effectiveness.

Conclusions: Recombinant L. casei combined with 5-ASA is effective in the treatment of DSS-induced colitis. The possible mechanism might be the blocking of the excessive activation of NF-κB pathway, thus suppressing the release of inflammation-related factors.
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http://dx.doi.org/10.1111/1751-2980.12006DOI Listing
February 2013

[Decitabine inhibits cell proliferation and induces apoptosis of all-trans retinoid acid-resistant acute promyelocytic leukemia NB4-R2 cell line].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2012 Feb;20(1):48-52

Department of Hematology, ThirSun Yat-Sen University, Guangzhou, Guangdong Province, China.

The aim of this study was to investigate the proliferation-inhibitory and inducing apoptotic effects of decitabine (DAC) on acute promyelocytic leukemia NB4-R2 cells. Cell inhibitory rate was determined by cell proliferation and cytotoxicity assay (WST-1 assay) after NB4-R2 cells were treated with 0.01 - 0.5 µmol/L DAC for 24, 48 and 72 h. Apoptosis of NB4-R2 cells treated with 0.05 - 5 µmol/L DAC for 48 h was detected by flow cytometry with PI staining and AnnexinV/PI staining. Reverse transcription-PCR (RT-PCR) was used to determine the mRNA expression level of MDR1 gene encoding P-glycoprotein (P-gp). The results indicated that DAC (0.01 - 0.5 µmol/L) inhibited the proliferation of NB4-R2 cells in both time- and concentration-dependent manners. The IC(50) of DAC on the viability of NB4-R2 cells after treatment for 48 and 72 h were 0.089 and 0.064 µmol/L respectively. DAC (0.05 - 5 µmol/L) induced NB4-R2 cell apoptosis in dose-dependent manner with down-regulation of MDR 1 gene expression. It is concluded that a low concentration of DAC (< 0.5 µmol/L) inhibits cell proliferation, while higher concentration of DAC (1 or 5 µmol/L) induces apoptosis on NB4-R2 cells, accompanied with reduction of MDR1 levels.
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February 2012