Publications by authors named "Zhenxia Zhang"

11 Publications

  • Page 1 of 1

The Mechanisms of Yu Ping Feng San in Tracking the Cisplatin-Resistance by Regulating ATP-Binding Cassette Transporter and Glutathione S-Transferase in Lung Cancer Cells.

Front Pharmacol 2021 28;12:678126. Epub 2021 May 28.

Division of Life Science, Center for Chinese Medicine, The Hong Kong University of Science and Technology, Kowloon, China.

Cisplatin is one of the first line anti-cancer drugs prescribed for treatment of solid tumors; however, the chemotherapeutic drug resistance is still a major obstacle of cisplatin in treating cancers. Yu Ping Feng San (YPFS), a well-known ancient Chinese herbal combination formula consisting of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, is prescribed as a herbal decoction to treat immune disorders in clinic. To understand the fast-onset action of YPFS as an anti-cancer drug to fight against the drug resistance of cisplatin, we provided detailed analyses of intracellular cisplatin accumulation, cell viability, and expressions and activities of ATP-binding cassette transporters and glutathione S-transferases (GSTs) in YPFS-treated lung cancer cell lines. In cultured A549 or its cisplatin-resistance A549/DDP cells, application of YPFS increased accumulation of intracellular cisplatin, resulting in lower cell viability. In parallel, the activities and expressions of ATP-binding cassette transporters and GSTs were down-regulated in the presence of YPFS. The expression of p65 subunit of NF-κB complex was reduced by treating the cultures with YPFS, leading to a high ratio of Bax/Bcl-2, i.e. increasing the rate of cell death. Prim-O-glucosylcimifugin, one of the abundant ingredients in YPFS, modulated the activity of GSTs, and then elevated cisplatin accumulation, resulting in increased cell apoptosis. The present result supports the notion of YPFS in reversing drug resistance of cisplatin in lung cancer cells by elevating of intracellular cisplatin, and the underlying mechanism may be down regulating the activities and expressions of ATP-binding cassette transporters and GSTs.
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http://dx.doi.org/10.3389/fphar.2021.678126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202081PMC
May 2021

Different clinical parameters inform epicardial fat thickness in pre- and post-menopausal women with obstructive sleep apnea.

BMC Womens Health 2021 06 11;21(1):239. Epub 2021 Jun 11.

Medical Imaging College, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.

Background: Obstructive sleep apnea (OSA) is a sleep-related disorder with breathing difficulties. Previous studies revealed that epicardial fat thickness (EFT) correlates with OSA severity. Interestingly, female patients display a stronger EFT-OSA correlation than males. The purpose of this study is to investigate the relationship between EFT and different clinical characteristics in pre- and post-menopausal women diagnosed with OSA.

Methods: Patients diagnosed with OSA were divided into pre/early peri-menopausal (Group 1) and post/late peri-menopausal (Group 2) according to the menopause status. EFT was obtained from parasternal long-axis echocardiographic images. We also collected general clinical characteristics of patients involved in this study, and performed spearman correlation analysis to explore the correlations between EFT and the general clinical characteristics. We further applied Multiple stepwise linear regression analysis to explore the predictors for EFT in both groups.

Results: A total number of 23 and 59 patients were enrolled in Group 1 and Group 2 respectively. EFT in Group 2 was significantly higher than that of Group 1. In both groups, EFT was positively correlated with apnea-hypopnea index (AHI), percentage of total sleep time when blood oxygen saturation was less than 90% (T90), oxygen desaturation index (ODI) and glucose; while EFT was negatively correlated with mean and lowest SaO (oxygen saturation) levels. However, EFT was positively correlated with total cholesterol (TC) only in Group 1 and body mass index (BMI) only in Group2, respectively. Multiple stepwise linear regression analysis showed that AHI was independently associated with EFT in Group 1. However, both AHI and BMI were independent predictors of EFT in Group 2.

Conclusion: EFT was notably correlated with menopausal status in women with OSA. AHI was the independent predictor of EFT in women with OSA. BMI was the independent predictor of EFT in post/late peri-menopausal women with OSA.
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http://dx.doi.org/10.1186/s12905-021-01384-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193883PMC
June 2021

Calycosin inhibits breast cancer cell migration and invasion by suppressing EMT via BATF/TGF-β1.

Aging (Albany NY) 2021 06 7;13(12):16009-16023. Epub 2021 Jun 7.

School of Life Sciences and Food Engineering, Hanshan Normal University, Chaozhou 521041, Guangdong, China.

In this study, we investigated the effects of calycosin on breast cancer cell progression and their underlying mechanisms. Calycosin dose- and time-dependently inhibited proliferation, migration, and invasion by T47D and MCF-7 breast cancer cells by downregulating basic leucine zipper ATF-like transcription factor (BATF) expression. Moreover, BATF promoted breast cancer cell migration and invasiveness by increasing TGFβ1 mRNA and protein levels. Bioinformatics analysis, dual luciferase reporter assays, and chromatin immunoprecipitation assays confirmed the presence of BATF-binding sites in the promoter sequence of gene. Calycosin treatment inhibited epithelial-mesenchymal transition (EMT) of breast cancer cells by significantly increasing E-cadherin levels and decreasing N-cadherin, Vimentin, CD147, MMP-2, and MMP-9 levels through downregulation of BATF and TGFβ1. TGFβ1 knockdown reduced the migration and invasiveness of BATF-overexpressing breast cancer cells, whereas incubation with TGFβ1 enhanced the migration and invasiveness of calycosin-treated breast cancer cells. Our findings demonstrated that calycosin inhibited EMT and progression of breast cancer cells by suppressing BATF/TGFβ1 signaling. This suggests calycosin would be a promising therapeutic option for breast cancer patients.
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http://dx.doi.org/10.18632/aging.203093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266341PMC
June 2021

The impact of left ventricular geometry on left atrium phasic function in obstructive sleep apnea syndrome: a multimodal echocardiography investigation.

BMC Cardiovasc Disord 2021 Apr 24;21(1):209. Epub 2021 Apr 24.

Medical imaging department of Shanxi Medical University; Department of Ultrasound, First Hospital of Shanxi Medical University, 85 Jiefang Nan Road, Taiyuan, 030001, Shanxi, China.

Background: Left ventricular geometry and left atrium (LA) enlargement are risk factors for cardiovascular disease. However, reports on the relationship between left ventricular geometry and LA volume yielded contradictory findings, and LA phasic function remains unclear. Hence, this study aimed to investigate the influence of left ventricular geometry on LA volume and phasic function in patients with obstructive sleep apnea syndrome (OSAS) via a multimodal echocardiographic approach.

Methods: In this cross-sectional study, 221 patients with OSAS (age 20-68 years, mean age 45.27 ± 12.50 years) underwent clinical evaluation, polysomnography, and multimodal echocardiographic examination with two-dimensional echocardiography (2DE), two-dimensional speckle-tracking echocardiography (2D-STE) and three-dimensional echocardiography (3DE). Based on conventional classification of left ventricular geometry, patients with OSAS were divided into four groups: normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH).

Results: Based on 2DE and 3DE, the LA volumes and indices gradually increased from NG to CH. Additionally, 2DE and 3DE LA maximum volume index (LAVImax) were higher in patients with CH and EH than in patients with NG and CR (P < 0.05). The reservoir function, estimated by LA total emptying fraction (LA TotEF) was lower in patients with CH than in patients with NG in 2DE and 3DE (both, P < 0.05). Also, LA conduit function, evaluated by LA passive emptying fraction (LA PassEF) was lower in patients with CH than in patients with NG and CR, and in patients with EH than in those with NG in 2DE and 3DE (all, P < 0.05). The LA booster pump function, evaluated by LA active emptying fraction (LA ActEF) showed no statistically significant difference in 2DE; however, it was greater in patients with CH than in those with NG in 3DE. Similar results were obtained by 2D-STE, and CH was significantly associated with LA strain during systole (LAS-S, β = - 0.546, 95%CI: - 6.371-(- 3.444); P < 0.001), early diastole (LAS-E, β = - 0.636, 95%CI: - 9.532-(- 5.710); P < 0.001), and late diastole (LAS-A, β = - 0.450, 95%CI: 1.518-3.909; P < 0.001) in multiple linear regression.

Conclusions: The LA phasic function changed with left ventricular geometry via multimodal echocardiography. CH had the most notable negative effect on the maximum volume and phasic function of the LA.
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http://dx.doi.org/10.1186/s12872-021-02018-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070276PMC
April 2021

Inhibition of tau aggregation and associated cytotoxicity on neuron-like cells by calycosin.

Int J Biol Macromol 2021 Feb 7;171:74-81. Epub 2020 Dec 7.

School of Food Engineering and Biotechnology, Hanshan Normal University, Chaozhou 521041, Guangdong, China. Electronic address:

In this study, the in vitro assembly of tau and anti-amyloidogenic properties of one naturally occurring phytoestrogen, calycosin, was investigated by spectroscopic techniques including ThT and ANS fluorescence, CD, Congo red absorbance as well as TEM analysis. Afterwards the cytotoxicity of different amyloid species against SH-SY5Y cells was evaluated by MTT assay. Fluorescence spectroscopic studies revealed that calycosin exerts its anti-amyloidogenic effects through increasing the lag time and reducing the apparent growth rate constant (k), the amount of fibrillation, and the exposure of hydrophobic regions. Congo red absorbance and CD studies indicated that calycosin prevented the formation of tau aggregate species and β-sheets structures, respectively. TEM analysis also determined the capacity of calycosin to inhibit tau fibrillogenesis through formation of large amorphous aggregates. Furthermore, cellular assays disclosed that calycosin mitigated the cell mortality, LDH release, ROS level, and expression of Bax, Bcl-2, and Caspase-3 in both mRNA and protein levels induced by tau amyloid fibrils. In conclusion, this data may suggest that calycosin can prevent tau amyloid fibrillation and the associated cytotoxicity, mainly due to its effects on formation of lower content of oligomeric and fibrillar aggregates with lower solvent-exposed hydrophobic patches compared to those produced in the absence of calycosin.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.12.030DOI Listing
February 2021

Directional axonal regrowth induced by an aligned fibrin nanofiber hydrogel contributes to improved motor function recovery in canine L2 spinal cord injury.

J Mater Sci Mater Med 2020 Apr 21;31(5):40. Epub 2020 Apr 21.

State Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, 100084, Beijing, China.

Spinal cord injuries (SCI) normally disrupt the long axonal tracts of the spinal cord and cause permanent neurological deficits, for which there is currently a lack of effective therapeutic methods. Biomaterial-based regenerative medicine is a pivotal strategy to induce axonal regeneration through delivery of biophysical and/or biochemical regulatory cues by biomaterials. We previously fabricated a hierarchically aligned fibrin hydrogel (AFG) that could promote neurogenic differentiation of stem cells in vitro and has been successfully applied for peripheral nerve and spinal cord regeneration in rats. In this study, AFG was used to repair a canine lumbar segment 2 hemisection spinal cord injury, and the consistency of histological, imageological and behavioral results was compared. AFG was used to construct an aligned fiber bridge that supported cell adhesion in vitro and rapidly facilitated tissue invasion along the long axis of fibers in vivo, Moreover, in vivo results demonstrated regrowth of axons in an oriented pattern connecting the rostral and caudal stumps. Consistent results were confirmed by diffusion tensor imaging, which allowed successful tracing of reconnected nerve fibers across the defect. As a result, directional axonal regrowth contributed to significantly improved recovery of motor functional behavior of SCI canines with AFG implantation. Our results suggest that AFG has great promise for rapidly directing axonal regrowth for nerve regeneration.
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http://dx.doi.org/10.1007/s10856-020-06375-9DOI Listing
April 2020

Identification of a Potent Enzyme for the Detoxification of Zearalenone.

J Agric Food Chem 2020 Jan 18;68(1):376-383. Epub 2019 Dec 18.

The occurrence of mycotoxin zearalenone (ZEN) and its derivatives has been a severe global threat to food and animals. In addition to the chemical and physical degradation methods, a powerful biocatalyst is urgently required for the detoxification of ZEN. Here, an efficient ZEN-degrading lactonase from , named ZENG, was identified for the first time. The recombinant ZENG exhibited the highest activity at pH 7.0 and 38 °C. In addition, the recombinant enzyme showed a high degrading performance toward ZEN and its toxic derivatives α-zearalenol (α-ZOL) and α-zearalanol (α-ZAL), with the specific activities as 315, 187, and 117 units/mg, respectively. To meet the industrial demands, attempts were also made to enhance the thermostability of ZENG using a structure-based modification. Three double-site mutants, including H134L/S136L, H134F/S136F, and H134I/S134I, in the position between the cap and core catalytic domain of ZENG were designed. Finally, the thermostability of both H134L/S136L and H134F/S136F displayed a significant improvement compared to the wild-type enzyme.
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http://dx.doi.org/10.1021/acs.jafc.9b06223DOI Listing
January 2020

Effect of hierarchically aligned fibrin hydrogel in regeneration of spinal cord injury demonstrated by tractography: A pilot study.

Sci Rep 2017 01 9;7:40017. Epub 2017 Jan 9.

Department of orthopedics, PLA General Hospital, BeiJing, 100853, China.

Some studies have reported that scaffold or cell-based transplantation may improve functional recovery following SCI, but no imaging information regarding regeneration has been provided to date. This study used tractography to show the regenerating process induced by a new biomaterial-aligned fibrin hydrogel (AFG). A total of eight canines subjected to SCI procedures were assigned to the control or the AFG group. AFG was implanted into the SCI lesion immediately after injury in 5 canines. A follow-up was performed at 12 weeks to evaluate the therapeutic effect including the hindlimb functional recovery, anisotropy and continuity of fibers on tractography. Using tractography, we found new fibers running across the SCI in three canines of the AFG group. Further histological examination confirmed limited glial scarring and regenerated nerve fibers in the lesions. Moreover, Repeated Measures Analysis revealed a significantly different change in fractional anisotropy (FA) between the two groups during the follow-up interval. An increase in FA during the post injury time interval was detected in the AFG group, indicating a beneficial effect of AFG in the rehabilitation of injured axons. Using tractography, AFG was suggested to be helpful in the restoration of fibers in SCI lesions, thus leading to promoted functional recovery.
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http://dx.doi.org/10.1038/srep40017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220328PMC
January 2017

Subcortical White Matter Changes with Normal Aging Detected by Multi-Shot High Resolution Diffusion Tensor Imaging.

PLoS One 2016 22;11(6):e0157533. Epub 2016 Jun 22.

Center for Biomedical Imaging Research, Department of Biomedical Engineering, Tsinghua University, Beijing, China.

Subcortical white matter builds neural connections between cortical and subcortical regions and constitutes the basis of neural networks. It plays a very important role in normal brain function. Various studies have shown that white matter deteriorates with aging. However, due to the limited spatial resolution provided by traditional diffusion imaging techniques, microstructural information from subcortical white matter with normal aging has not been comprehensively assessed. This study aims to investigate the deterioration effect with aging in the subcortical white matter and provide a baseline standard for pathological disorder diagnosis. We apply our newly developed multi-shot high resolution diffusion tensor imaging, using self-feeding multiplexed sensitivity-encoding, to measure subcortical white matter changes in regions of interest of healthy persons with a wide age range. Results show significant fractional anisotropy decline and radial diffusivity increasing with age, especially in the anterior part of the brain. We also find that subcortical white matter has more prominent changes than white matter close to the central brain. The observed changes in the subcortical white matter may be indicative of a mild demyelination and a loss of myelinated axons, which may contribute to normal age-related functional decline.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157533PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917173PMC
July 2017

Average over depth during optical mapping of cardiac propagation.

Conf Proc IEEE Eng Med Biol Soc 2005;2005:4314-6

The key Laboratory of Biomedical Information of Ministry of Education of China; The School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P.R.China; The School of Electrical Engineering, Xi'an Jiaotong University, Xi'an 710049, P.R.China.

High-resolution optical mapping with voltagesensitive dyes has become a powerful tool to depict complex propagation patterns of cardiac transmembrane potentials. Many studied have proved that this optical signal obtained from tissue surface is the response of the transmembrane potential averaged upon depth rather than only surface. In order to investigate the differentia between the two transmembrane potentials, in this paper, we simulated cardiac propagation using Luo-Rudy (L-R) model and calculated the transmembrance potentials average over depth by an optical decay constant from 0.0 mm to 3.0mm. Our results suggest that the transmembrance potentials weighted average over depth is different from that on the tissue surface, the discrepancy between them depends on the depth of the fluorescence emission of the tissue. If only top layer of tissue (<1.0mm) contributes the fluorescence, optical mapping is an almost accurate representation of surface activation dynamics.
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http://dx.doi.org/10.1109/IEMBS.2005.1615419DOI Listing
October 2012

A new nitroethylphenolic glycoside from Semiaquilegia adoxoides.

Fitoterapia 2004 Jun;75(3-4):420-2

College of Pharmaceuticals and Biotechnology, Tianjin University, Tianjin 300072, PR China.

The isolation of a new nitroethylphenolic glycoside, 4-hydroxy-1-(2-nitroethyl) benzene 4-O-(6'-O-beta-D-xylopyranosyl)-beta-D-glucopyranoside (1), from the roots of Semiaquilegia adoxoides is reported.
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http://dx.doi.org/10.1016/j.fitote.2004.01.016DOI Listing
June 2004
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