Hui Wang

Publications (8)21.91 Total impact

• Article: BF-30 selectively inhibits melanoma cell proliferation via cytoplasmic membrane permeabilization and DNA-binding in vitro and in B16F10-bearing mice.

  Hui Wang, Mengyun Ke, Yuwei Tian, Jing Wang, Bing Li, Yizhou Wang, Jie Dou, Changlin Zhou
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  ABSTRACT: Cathelicidin-BF (BF-30) is a cathelicidin-like polypeptide composed of 30 amino acids and is a natural antibacterial peptide extracted from the venom of the snake Bungarus fasciatus. In our previous study, BF-30 showed broad antimicrobial activity against drug-resistant bacteria through enhancing the cytoplasmic membrane permeability. However, the anticancer activity of BF-30 has not yet been investigated. In this study, the effects of BF-30 on the proliferation of the metastatic melanoma cell line B16F10 in vitro and in vivo, as well as the mechanism were studied. Assay of cell viability, a B16F10-bearing mouse model, and histochemical examination were utilized to investigate the anti-tumor effects of BF-30. In addition, transmission electron microscope analysis, lactate dehydrogenase release assay, DNA retardation assay, Real-time PCR, Western blot, wound healing assay, and chick embryo chorioallantoic membrane assay were applied to elucidate the mechanism of BF-30 on B16F10. BF-30 inhibited B16F10 and B16 proliferation in vitro in a dose- and time-dependent manner with an IC50 of 7.3µM and 13.9µM, respectively. Moreover, BF-30 significantly suppressed melanoma growth in B16F10-bearing mice without body weight loss. The observed inhibition were 41.4%, 49.5% and 63.5% at the doses of 0.75, 1.5 and 3mg/kg/day, respectively. This inhibition of metastatic melanoma cell proliferation was partially dependent on disrupting the cytoplasmic membrane, binding to genomic DNA, preventing transcription and translation of the VEGF gene. This inhibition restrained B16F10 migration and angiogenesis. These results further suggest that BF-30 may be a candidate for the treatment of malignant melanoma.
  European journal of pharmacology 03/2013; · 2.59 Impact Factor
• Article: Effective antimicrobial activity of Cbf-K(16) and Cbf-A(7) A(13) against NDM-1-carrying Escherichia coli by DNA binding after penetrating the cytoplasmic membrane in vitro.

  Qingru Hao, Hui Wang, Jing Wang, Jie Dou, Min Zhang, Weidong Zhou, Changlin Zhou
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  ABSTRACT: New Delhi metallo-beta-lactamase-1(NDM-1)-carrying isolates, which are resistant to most clinical used antibiotics except for tigecycline and colistin, have been found worldwide. Cathelicidin-BF (BF-30) is found in the venom of the snake Bungarus fasciatus and exhibits broad antimicrobial activity. Cbf-K(16) and Cbf-A(7) A(13) were obtained by mutating Lys(16) , Ala(7) , and Ala(13) of BF-30, respectively. To investigate their antimicrobial activities against NDM-1 carrying bacteria, recombinant Escherichia coli BL21 (DE3)-NDM-1 with high NDM-1 activity was constructed by inserting the Klebsiella pneumoniae NDM-1 gene (GenBank accession no. HQ328085) into a pET28a vector and transforming it into E. coli BL21 (DE3). The peptides showed effective antimicrobial activities against NDM-1-carrying E. coli, and the minimum inhibitory concentrations of Cbf-K(16) and Cbf-A(7) A(13) were only 4 and 8 µg/ml, whereas those of minimum bactericidal concentrations were 8 and 16 µg/ml, respectively. A time course experiment showed that colony forming unit counts rapidly decreased, and bacteria were thoroughly eliminated within 3 and 6 h by the Cbf-K(16) and Cbf-A(7) A(13) treatments, respectively. The peptides penetrated the bacterial cell membrane and enabled β-galactosidase leakage, and caused the cytoplasmic membrane to become permeable, and finally bound to the DNA. The genomic DNA of E. coli was completely unable to migrate on an agarose gel after Cbf-K(16) treatment (8 µg/ml). These data demonstrated that Cbf-K(16) and Cbf-A(7) A(13) possess effective antimicrobial activity against drug-resistant strains, including NDM-1 carrying E. coli BL21 (DE3)-NDM-1, by binding to DNA after penetrating the cytoplasmic membrane in vitro, which may have potential therapeutic value for the treatment of NDM-1-carrying bacterial infections. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
  Journal of Peptide Science 02/2013; · 1.80 Impact Factor
• Article: Deletion of the aroK gene is essential for high shikimic acid accumulation through the shikimate pathway in E. coli.

  Kai Chen, Jie Dou, Shirui Tang, Yishun Yang, Hui Wang, Hongqing Fang, Changlin Zhou
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  ABSTRACT: Shikimic acid (SA) is an important metabolic intermediate with diverse commercial applications. In this work, antisense RNA interference and gene deletion were carried out to inactivate the aroK gene in an SA-producing Escherichia coli strain, DHPYA-T7. In this strain, the aroL, ptsHIcrr and ydiB genes are deleted, and the tktA, glk, aroE and aroB genes are overexpressed. Flask cultivations of the DHPYA-T7 derivative strains showed that the accumulation of SA increased 2.69-fold after aroK gene deletion (DHPYAAS-T7) and 1.29-fold after antisense RNA interference (DHPYAS-T7). Furthermore, the activity of shikimate kinase in DHPYAAS-T7 was 0.21-fold of that in strain DHPYAS-T7. In a 10-L fermentation, SA accumulation increased to 1850 mg L(-1) in strain DHPYAAS-T7, which is a 1.5-fold increase over that in strain DHPYAS-T7. These results demonstrate that aroK gene inactivation in DHPYA-T7 leads to high SA accumulation, especially when this inactivation is caused by chromosomal deletion.
  Bioresource technology 05/2012; 119:141-7. · 4.25 Impact Factor
• Article: Synergistic activity of baicalein with ribavirin against influenza A (H1N1) virus infections in cell culture and in mice.

  Lili Chen, Jie Dou, Zhenzhen Su, Huimin Zhou, Hui Wang, Weidong Zhou, Qinglong Guo, Changlin Zhou
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  ABSTRACT: Baicalein is a flavonoid derived from the root of Scutellaria baicalensis, a traditional Chinese medicine that has been used for hundreds of years; baicalein has also been demonstrated to have antiviral activity with low toxicity. The synergistic activity of baicalein with ribavirin against influenza virus infections in cell culture and in mice was investigated for the first time in our research. In vitro, maximal synergy at lower concentrations of baicalein (0.125 μg/ml) and ribavirin (12.5 μg/ml) was observed, and the reduced expression of the viral matrix protein (M) gene suggested that drug combinations caused greater inhibition than ribavirin alone, especially the combination of 0.5 μg/ml baicalein and 5 μg/ml ribavirin. In vivo, combinations of baicalein and ribavirin provided a higher survival rate and lower body weight loss. Moreover, fewer inflammatory responses in the lungs of mice infected with virus and treated with baicalein and ribavirin were observed; the mean scores were 1.0, 0.8, and 1.2 with the doses of ribavirin at 50 mg/kg/d combined with baicalein at 100 mg/kg/d, 200 mg/kg/d, and 400 mg/kg/d respectively, while the placebo group had a mean pathology score of 3.2. Thus, the data demonstrates that combinations of baicalein and ribavirin provide better protection against influenza infection than each compound used alone and could potentially be clinically useful.
  Antiviral research 09/2011; 91(3):314-20. · 3.61 Impact Factor
• Article: Effective inhibition of a Strongylocentrotus nudus eggs polysaccharide against hepatocellular carcinoma is mediated via immunoregulation in vivo.

  Mengyu Wang, Hui Wang, Ying Tang, Di Kang, Yu Gao, Mengyun Ke, Jie Dou, Tao Xi, Changlin Zhou
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  ABSTRACT: This study was aimed at evaluating the inhibitory effect of a polysaccharide that was isolated from Strongylocentrotus nudus eggs (SEP) against hepatocellular carcinoma in H22-bearing mice and elucidating its immunological mechanisms by determining its effects on the growth of transplanted tumors and immune response in H22-bearing mice. ICR mice inoculated with mouse hepatoma carcinoma cell lines H22 were treated with SEP at doses of 4, 8, 16 mg/kg/d for 12 days. The effects of SEP were measured via the growth of the transplanted tumors, splenocyte proliferation, T lymphocytes counts, CTL activity, the production of cytokines from splenocytes and the levels of serum Ig in tumor-bearing mice. In addition, the effects of SEP on Erk phosphorylation in mouse splenocytes and on the transcriptional activity of NFAT in Jurkat T cells were also investigated. Our results showed that SEP significantly inhibited the growth of transplanted tumors in mice. SEP could not only remarkably enhance splenocyte proliferation, CD4(+) and CD8(+) T cell numbers as well as CTL activity, but it also elevated IL-2 and TNF-α secretion as well as IgA, IgM and IgG levels in the serum. Furthermore, the activation of Erk phosphorylation and the NFAT promoter by SEP promoted the transcription and expression of downstream gene IL-2. In conclusion, our study demonstrates that SEP effectively inhibits hepatocellular carcinoma in vivo via enhancement of host immune system function, and it could be a potential therapeutic drug for hepatocarcinoma.
  Immunology letters 08/2011; 141(1):74-82. · 2.91 Impact Factor
• Article: A polysaccharide from Strongylocentrotus nudus eggs protects against myelosuppression and immunosuppression in cyclophosphamide-treated mice.

  Hui Wang, Mengyu Wang, Jing Chen, Ying Tang, Jie Dou, Jian Yu, Tao Xi, Changlin Zhou
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  ABSTRACT: To assess the chemoprotective properties of a polysaccharide from Strongylocentrotus nudus eggs (SEP), myelosuppressed and immunosuppressed mouse models were generated by administration of cyclophosphamide (Cy) and then treated with SEP. SEP (16 mg/kg/d) remarkably increased spleen and thymus indices, activated the proliferation of leukocytes and erythrocytes and platelets from peripheral blood, and exhibited co-mitogenic activity on ConA- or LPS-stimulated splenocytes in a dose-dependent manner. An increased percentage of CD34(+) cells in bone marrow of Cy-treated mice was also observed. Furthermore, SEP elevated CD4(+) T lymphocyte counts as well as the CD4/CD8 ratio dose-dependently, and it increased interleukin-2 (IL-2), IgA, IgM, and IgG levels in the sera of Cy-treated mice. Pre-incubation with TLR2 and TLR4 blocking antibodies inhibited splenocyte proliferation and its IL-2 secretion. Finally, SEP significantly induced Akt phosphorylation in splenocytes from Cy-treated mice, suggesting that chemoprotection by SEP was mediated through the PI3K/Akt signaling pathway. These findings indicate that SEP plays an important role in the protection against myelosuppression and immunosuppression in Cy-treated mice and could be a potential immunomodulatory agent.
  International immunopharmacology 06/2011; 11(11):1946-53. · 2.21 Impact Factor
• Article: The antibacterial activity of BF-30 in vitro and in infected burned rats is through interference with cytoplasmic membrane integrity.

  Huimin Zhou, Jie Dou, Jing Wang, Lili Chen, Hui Wang, Weidong Zhou, Yunman Li, Changlin Zhou
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  ABSTRACT: Cathelicidin-BF (BF-30) is found in the venom of the snake Bungarus fasciatus and exhibits broad antimicrobial activity against bacteria and fungi. Nevertheless, its antibacterial activity in vivo and antibacterial mechanism is unknown. In the present study, we examined the antibacterial activity of BF-30 in vitro against drug-resistant Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, first identifying its protection against P. aeruginosa in infected burns and then delineating the antimicrobial mechanism of BF-30. The data showed that BF-30 had stronger antimicrobial activities against a broad spectrum of microorganisms than gentamicin, ampicillin or bacitracin. The killing curves of BF-30 against P. aeruginosa and S. aureus showed that CFU counts rapidly decreased by almost 2 logs within 6min, and it took just less than 2h to kill all the bacteria. In addition, we investigated whether BF-30 had antibacterial activity in a burn/acute infection rat model. Dose-response (0.75, 3, 12mg/kg/day) studies indicated that BF-30 significantly reduced the colonization of P. aeruginosa in the burn eschars, lungs and liver of burn injured rats and that it could prevent subsequent systemic infection and development of inflammation. The peptide induced chaotic membrane morphology and cell debris, as determined by electron microscopy, and caused the cytoplasmic membrane to crack, resulting in β-galactosidase leakage and EtBr accumulation. This suggests that the antimicrobial activity of BF-30 is based on cytoplasmic membrane permeability. Taken together, our data demonstrate that antibacterial activity of BF-30 has potential therapeutic value for the prevention and treatment of burn and wound infections.
  Peptides 06/2011; 32(6):1131-8. · 2.43 Impact Factor
• Article: Effects of baicalein on Sendai virus in vivo are linked to serum baicalin and its inhibition of hemagglutinin-neuraminidase.

  Jie Dou, Lili Chen, Ge Xu, Lei Zhang, Huimin Zhou, Hui Wang, Zhenzhen Su, Mengyun Ke, Qinglong Guo, Changlin Zhou
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  ABSTRACT: Parainfluenza viruses are significant respiratory-tract pathogens that are notorious for infecting children. However, there are no clinical drugs to control the infection caused by these viruses. Sendai virus (SeV) belongs to the family Paramyxoviridae and causes fatal pneumonia in mice, its natural host. Baicalein is a flavonoid derived from the root of Scutellaria baicalensis, which is a traditional Chinese medicine that has been used for hundreds of years and has demonstrated a variety of biological activities. Our findings reveal that oral administration of baicalein to mice infected with Sendai virus results in a significant reduction in virus titers in the lungs and protection from death. The in vivo inhibitory effects of baicalein on Sendai virus are determined by baicalin in the serum. The mean IC(50) of baicalin was 0.71 μg/ml in an HA inhibition assay and 3.22 μg/ml in an NA inhibition assay. The mean IC(50) of baicalin in a CPE assay was measured to be 0.70 μg/ml, and significant inhibition was observed in a plaque assay at a concentration of 1.6 μg/ml baicalin in overlay medium, which suggests that baicalein is a potential anti-parainfluenzaviral agent in vivo.
  Archives of Virology 02/2011; 156(5):793-801. · 2.11 Impact Factor