Publications by authors named "Shi-Bing Zhang"

9 Publications

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Phytochemical library screen reveals betulinic acid as a novel Skp2-SCF E3 ligase inhibitor in non-small cell lung cancer.

Cancer Sci 2021 Jun 3. Epub 2021 Jun 3.

Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.

Skp2 is overexpressed in multiple cancers and plays a critical role in tumor development through ubiquitin/proteasome-dependent degradation of its substrate proteins. Drugs targeting Skp2 have exhibited promising anticancer activity. Here, we identified a plant-derived Skp2 inhibitor, betulinic acid (BA), via high-throughput structure-based virtual screening of a phytochemical library. BA significantly inhibited the proliferation and migration of non-small cell lung cancer (NSCLC) through targeting Skp2-SCF E3 ligase both in vitro and in vivo. Mechanistically, BA binding to Skp2, especially forming H-bond with residue Lys145, decreases its stability by disrupting Skp1-Skp2 interactions, thereby inhibiting the Skp2-SCF E3 ligase and promoting the accumulation of its substrates, that is, E-cadherin and p27. In both subcutaneous and orthotopic xenografts, BA significantly inhibited the proliferation and metastasis of NSCLC through targeting Skp2-SCF E3 ligase and upregulating p27 and E-cadherin protein levels. Taken together, BA can be considered a valuable therapeutic candidate to inhibit metastasis of NSCLC.
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http://dx.doi.org/10.1111/cas.15005DOI Listing
June 2021

Identification of pseudolaric acid B as a novel Hedgehog pathway inhibitor in medulloblastoma.

Biochem Pharmacol 2021 May 6;190:114593. Epub 2021 May 6.

Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China; Research Center of Chinese Herbal Resources Science and Engineering, School of Pharmaceutical Sciences; Key Laboratory of Chinese Medicinal Resource from Lingnan, Ministry of Education, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address:

Aberrant activation of the Hedgehog (Hh) pathway is implicated in the pathogenesis and development of multiple cancers, especially Hh-driven medulloblastoma (MB). Smoothened (SMO) is a promising therapeutic target of the Hh pathway in clinical cancer treatment. However, SMO mutations frequently occur, which leads to drug resistance and tumor relapse. Novel inhibitors that target both the wild-type and mutant SMO are in high demand. In this study, we identified a novel Hh pathway inhibitor, pseudolaric acid B (PAB), which significantly inhibited the expression of Gli1 and its transcriptional target genes, such as cyclin D1 and N-myc, thus inhibiting the proliferation of DAOY and Ptch1 primary MB cells. Mechanistically, PAB can potentially bind to the extracellular entrance of the heptahelical transmembrane domain (TMD) of SMO, based on molecular docking and the BODIPY-cyclopamine binding assay. Further, PAB also efficiently blocked ciliogenesis, demonstrating the inhibitory effects of PAB on the Hh pathway at multiple levels. Thus, PAB may overcome drug-resistance induced by SMO mutations, which frequently occurs in clinical setting. PAB markedly suppressed tumor growth in the subcutaneous allografts of Ptch1 MB cells. Together, our results identified PAB as a potent Hh pathway inhibitor to treat Hh-dependent MB, especially cases resistant to SMO antagonists.
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http://dx.doi.org/10.1016/j.bcp.2021.114593DOI Listing
May 2021

[Pollution Characteristics, Source Analysis and Potential Ecological Risk Assessment of Heavy Metals in Soils Surrounding a Municipal Solid Waste Incineration Plant in Shanghai].

Huan Jing Ke Xue 2017 Dec;38(12):5262-5271

State Environmental Protection Engineering Center for Pollution Treatment and Control in Textile Industry, College of Environmental Science and Engineering, Donghua University, Shanghai 201620, China.

The contents of ten heavy metals (As, Cu, Cd, Cr, Pb, Ni, Zn, Ti, Mn, and Hg) were determined in the surface soils surrounding a municipal solid waste incineration plant in Shanghai using atomic spectroscopy. The spatial distribution and sources of the detected heavy metals were studied by enrichment factor and multivariate statistical and spatial interpolation analyses. In addition, their potential ecological risk was assessed. The results showed that all heavy metals, except Hg and As, were detected with mean contents ranging from 0.399 to 4220 mg·kg. The mean contents of Cu, Cd, Cr, Pb, Ni, Zn, and Mn were higher than their respective background values in Shanghai. In particular, the mean content of Cd was 2.9 times its background value. The results of the Pearson's correlation, principle component, enrichment factor, and spatial distribution analyses of these heavy metals indicated that Ti, Mn, and Ni primarily originated from natural sources, while Cd, Cr, Cu, Pb, and Zn originated from industrial manufacturing, combustion, and traffic emissions. The potential ecological risk assessment showed that soils surrounding the municipal solid waste incineration plant suffered from a moderate-level risk. The mean value of the potential ecological risk index of these detected heavy metals was 108.92, of which Cd contributed as high as 79.63%, deserving much attention.
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http://dx.doi.org/10.13227/j.hjkx.201704113DOI Listing
December 2017

Perceptions of Chinese Biomedical Researchers Towards Academic Misconduct: A Comparison Between 2015 and 2010.

Sci Eng Ethics 2018 04 10;24(2):629-645. Epub 2017 Apr 10.

Medjaden Bioscience Limited, Room 2001-4, China Insurance Group Building, 141 Des Voeux Road Central, Hong Kong, China.

Publications by Chinese researchers in scientific journals have dramatically increased over the past decade; however, academic misconduct also becomes more prevalent in the country. The aim of this prospective study was to understand the perceptions of Chinese biomedical researchers towards academic misconduct and the trend from 2010 to 2015. A questionnaire comprising 10 questions was designed and then validated by ten biomedical researchers in China. In the years 2010 and 2015, respectively, the questionnaire was sent as a survey to biomedical researchers at teaching hospitals, universities, and medical institutes in mainland China. Data were analyzed by the Chi squared test, one-way analysis of variance with the Tukey post hoc test, or Spearman's rank correlation method, where appropriate. The overall response rates in 2010 and 2015 were 4.5% (446/9986) and 5.5% (832/15,127), respectively. Data from 15 participants in 2010 were invalid, and analysis was thus performed for 1263 participants. Among the participants, 54.7% thought that academic misconduct was serious-to-extremely serious, and 71.2% believed that the Chinese authorities paid no or little attention to the academic misconduct. Moreover, 70.2 and 65.2% of participants considered that the punishment for academic misconduct at the authority and institution levels, respectively, was not appropriate or severe enough. Inappropriate authorship and plagiarism were the most common forms of academic misconduct. The most important factor underlying academic misconduct was the academic assessment system, as judged by 50.7% of the participants. Participants estimated that 40.1% (39.8 ± 23.5% in 2010; 40.2 ± 24.5% in 2015) of published scientific articles were associated with some form of academic misconduct. Their perceptions towards academic misconduct had not significantly changed over the 5 years. Reform of the academic assessment system should be the fundamental approach to tackling this problem in China.
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http://dx.doi.org/10.1007/s11948-017-9913-3DOI Listing
April 2018

Influence of Chitosan Nanoparticles as the Absorption Enhancers on Salvianolic acid B In vitro and In vivo Evaluation.

Pharmacogn Mag 2016 Jan-Mar;12(45):57-63

Department of Pharmacy, The SuqianFirst Hospital, Suqian, Jiangsu 223800, China.

Background: Salvianolic acid B (SalB) represents the most abundant and bio-active phenolic constituent among the water-soluble compounds of Salvia miltiorrhiza. But the therapeutic potential of SalB has been significantly restricted by its poor absorption.

Methods: In this study, chitosans (CS) and CS nanoparticles (NPs) with different molecular weights (MWs), which have influence on the absorption of SalB, was also investigated.

Results: As a preliminary study, water-soluble CS with various MWs (3, 30, 50, and 100 kDa) was chosen. We investigated the MW-dependent Caco-2 cell layer transport phenomena in vitro of CS and NPs at concentrations (4 μg/ml, w/v). SalB, in presence CS or NPs has no significant toxic effect on Caco-2 cell. As the MW increases, the absorption enhancing effect of CS increases. However, as the MW decreases, the absorption enhancing effect of NPs increases. The AUC0-∞ of the SalB-100 kDa CS was 4.25 times greater than that of free SalB. And the AUC0-∞ of the SalB-3 kDa NPs was 16.03 times greater than that of free SalB.

Conclusion: CS and NPs with different MWs as the absorption enhancers can promote the absorption of SalB. And the effect on NPs is better than CS.

Summary: Formation mechanism for NPs.
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http://dx.doi.org/10.4103/0973-1296.176047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4787338PMC
March 2016

The chelation targeting metal-Aβ40 aggregates may lead to formation of Aβ40 oligomers.

Dalton Trans 2011 May 24;40(18):4830-3. Epub 2011 Mar 24.

Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, School of Chemistry, Central China Normal University, Wuhan, 430079, P. R. China.

The fluorescent chelator (FC-1) was designed by combining a metal-chelating unit and a ThT-based Aβ aggregate-binding fluorescent unit. FC-1 is a cell membrane-penetrable chelator with a moderate chelation ability to Cu(2+) and Zn(2+) and can target metal-Aβ40 aggregates. Treatment with FC-1 led to enhanced cytotoxicity of the aggregates, because the aggregates were converted into a pool of oligomers.
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http://dx.doi.org/10.1039/c1dt00020aDOI Listing
May 2011

Right ventricular dysfunction due to right ventricular outflow tract patch.

Asian Cardiovasc Thorac Ann 2006 Jun;14(3):213-8

Department of Cardiovascular Surgery, 1st Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui 230022, China.

Doppler tissue imaging analysis was used to examine the relationship between right ventricular function and right ventricular outflow tract damage in 54 patients with repaired tetralogy of Fallot. The patients were divided into three groups: 16 in whom the right ventricular outflow tract was directly sutured (group DS), 23 who had transventricular patch repair (group TVP), and 15 who had transannular patch repair (group TAP). The control group consisted of 16 age-matched patients who underwent patch closure of a ventricular septal defect (group C). The Tei index was obtained from tricuspid and pulmonary Doppler flow velocities. The right ventricular Tei index was significantly greater in groups TVP and TAP than in group DS. Doppler tissue imaging analysis in groups TVP and TAP showed shorter myocardial systolic velocity, diastolic peak velocity, and atrial diastolic peak velocity, lower peak myocardial velocity and acceleration during isovolumic contraction, and prolonged isovolumic relaxation and contraction times compared to groups DS and C. Right ventricular dysfunction is due to the right ventricular outflow tract patch. Thus, the right ventricular outflow tract may be essential for right ventricular ejection and maintenance of right ventricular function.
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http://dx.doi.org/10.1177/021849230601400309DOI Listing
June 2006

Ventricular septal defect closure in right coronary cusp prolapse and aortic regurgitation complicating VSD in the outlet septum: which treatment is most appropriate?

Heart Lung Circ 2006 Jun 11;15(3):168-71. Epub 2006 May 11.

Department of Cardiovascular Surgery, 1st Hospital of Anhui Medical University, Hefei, 218 Jixi Road, Hefei, Anhui 230022, China.

Background: There is currently not a standardized technique for the sizing and shaping of surgical closure of the ventricular septal defect (VSD) patch in patients with right coronary aortic cusp prolapse and aortic regurgitation (AR) complicating VSD in the outlet septum.

Methods: Forty-six VSD patients who had aortic valve prolapse were divided into groups DC (direct closure, n=19), and SPC (small patch closure, n=27). Preoperative and postoperative echocardiography with Doppler color flow interrogation was performed on all patients.

Results: In the DC group, among seven patients who had aortic valve prolapse but no AR preoperative, one patient developed AR during postoperative follow-up period. In the remaining 12 patients who had mild AR associated with aortic valve prolapse prior to the procedure, AR was diminished in four and unchanged in six patients. However, AR was aggravated in two patients who required further operations for AV repair or replacement. In the SPC group, among the eight patients who had no preoperative AR, AR progressed in one patient postoperatively. In the remaining 19 patients who had mild AR, AR was diminished in 15 and unchanged in four. The outcome from the operative procedure was significantly better in the SPC group than DC group with mild preoperative AR (chi(2)=7.82; P<0.05).

Conclusions: Small patch closure for this type of VSD is safer and more reliable in improving mild AR than that of direct closure, especially in patients with mild AR.
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http://dx.doi.org/10.1016/j.hlc.2005.10.006DOI Listing
June 2006

[Clinical evaluation of the heart function early after repair of tetralogy of Fallot: follow-up of 43 patients].

Zhonghua Yi Xue Za Zhi 2006 Feb;86(6):407-10

Department of Cardiovascular Surgery, First Hospital of Anhui Medical University, Hefei 230022, China.

Objective: To evaluate the heart function of the patients early after the repair of tetralogy of Fallot (TOF).

Methods: Forty-three patients with TOF, 25 males and 18 females, underwent operation at the age of 2.5 - 52 years (16.7 years on average) and were followed up for 1 - 3.5 years. Twenty-one age-matched healthy persons were used as controls. Tissue Doppler imaging (TDI) was used to measure the values of the peak tricuspid ring velocity during early diastole (Ea), late diastole (Aa), systole, and isovolumic contraction, and isovolumetric contraction acceleration (IVA); and isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and isovolumetric contraction velocity (IVV) of the right ventricle. Tei index was calculated using the formula: (ICT + IRT)/ET. Treadmill test was used on the patients aged > 17 to measure the maximal heart rate maximal blood pressure, maximal exercise tolerance (MET), and movement time.

Results: The peak tricuspid ring velocity during Ea of the repaired TOF group (rTOF group) was 11.5 +/- 2.6 cm/s, significantly lower than that of the control group (17.1 +/- 2.4 cm/s, P < 0.0001), the peak tricuspid ring velocity during Aa of the rTOF group was 9.6 +/- 1.7 cm/s, significantly lower than that of the control group (12.9 +/- 2.9 cm/s, P < 0.001), the E/A of the rTOF group was 1.16 +/- 0.36, significantly lower than that of the control group (1.36 +/- 0.26, P < 0.05). The IVV of the rTOF group was 7.7 +/- 1.8 cm/s, significantly lower than that of the control group (9.9 +/- 1.4 cm/s, P = 0.0030, and the IVA of the rTOF group was 131.7 +/- 37.6 cm/s(2), significantly lower than that of the control group (222.5 +/- 39.2 cm/s(2), P < 0.001). The Tei index of the rTOF group was 0.58 +/- 0.11, significantly higher than that of the control group (0.52 +/- 0.04, P = 0.029). The maximal heart rate maximal blood pressure, MET, and movement time of the rTOF group were all significantly lower than those of the control group (P < 0.05 or P < 0.01).

Conclusion: The heart function of the patients undergoing repair of TOF fails to recover to the normal level during a short time after the surgery.
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February 2006