Publications by authors named "Xiu-Zhen Wu"

13 Publications

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Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer.

EBioMedicine 2021 Nov 21;74:103714. Epub 2021 Nov 21.

State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address:

Background: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management.

Methods: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280-473 days), and an independent case-control study from Beijing (n = 99).

Findings: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78-0.99) vs. 0.56 (0.36-0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins.

Interpretation: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention.

Funding: The funders are listed in the Acknowledgement.
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http://dx.doi.org/10.1016/j.ebiom.2021.103714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617343PMC
November 2021

[Analysis of assessment results of malaria elimination in Suzhou City].

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2018 Apr;30(6):698-701

Suzhou Municipal Center for Disease Control and Prevention, Jiangsu Province, Suzhou 215004, China.

Objective: To analyze the assessment results of malaria elimination in Suzhou City, so as to provide references for consolidating the results of malaria elimination in the city.

Methods: According to "Jiangsu Province Malaria Evaluation and Assessment Implementation Plan (2014 Edition)" and "Jiangsu City Malaria Evaluation Implementation Regulations (2015 Edition)", the assessment of the county-level cities and districts under the jurisdiction of Suzhou City was conducted. After the assessment, the municipal level assessment and evaluation were carried out, and one district was randomly selected for the assessment of malaria elimination review.

Results: The assessment score of malaria elimination in Suzhou City was 98.6 points. Wujiang District was randomly selected for review assessment, and the review score was 95.8 points. According to the 85 points attainment criteria specified by the national assessment, Suzhou City met the requirement of malaria elimination.

Conclusions: Suzhou City has passed the inspection certification of malaria elimination in Jiangsu Province. However, the post-elimination malaria monitoring should be continued to consolidate the achievements.
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http://dx.doi.org/10.16250/j.32.1374.2018084DOI Listing
April 2018

[Significant impact of different induction conditions on metabolic diversity of callus cell lines of Glycyrrhiza sp].

Zhongguo Zhong Yao Za Zhi 2013 Dec;38(23):4056-60

The purpose of this study was to evaluate the impact of callus induction and culture conditions on secondary metabolic diversity of the callus cell lines of traditional Chinese medicinal plant Glycyrrhiza sp. (Glycyrrhiza) by combined chemical analysis and HPLC fingerprint. These callus induction conditions included two Glycyrrhiza species, two types of explants, light and dark conditions, and two combinations of hormones. The evaluation was firstly based on the contents of total flavonoids in the callus by chemical analysis and one way ANOVA. The content of total flavonoids in callus was significantly (P < 0.05) influenced by Glycyrrhiza species, light condition, and the combination of hormones. The callus was further evaluated using diversity factor based on the comparison of HPLC fingerprints of these callus cell lines. Diversity factor varies significantly for calli induced under different conditions, with the highest being at 0.45 under light condition and combination of hormones. These results provide important knowledge for the selection of suitable callus cell lines for the production of pharmacologically important secondary metabolites or bioactive fractions by in vitro culture of Glycyrrhiza sp.
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December 2013

[Epidemic trend of malaria in Suzhou City, Jiangsu Province, China from 2007 to 2012].

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2013 Aug;25(4):435-6

Suzhou Center for Disease Prevention and Control, Jiangsu Province, Suzhou 215004, China.

Objective: To understand the epidemic trend of malaria in Suzhou City, Jiangsu Province, so as to provide the evidence for developing the strategies of malaria elimination.

Methods: The malaria information was collected from 2007 to 2012 through the reporting system of Suzhou epidemic information network and parasitic network system, and the results were analyzed statistically.

Results: From 2007 to 2012, there were 318 malaria cases reported. Among them, 28 cases (8.81%) were local residents with vivax malaria, and the annual incidence rate was 0.07/10(5). Among the floating population, there were 290 malaria cases (91.19%) and the annual incidence rate was 0.77/10(5), including 233 vivax malaria cases, 20 falciparum malaria cases, 1 ovale malaria case, and 1 mixed infection case. The malaria incidence rate of local residents dropped year by year in the past 6 years while that of floating populations increased. During the period of the later 3 years, no local malaria case was found.

Conclusion: The malaria has been eliminated among the local residents while the malaria cases from floating populations increased. Therefore, we should strengthen the cross-regional joint malaria control and prevention, and the malaria management of entry-exit persons.
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August 2013

[Thyroid follicular carcinoma-like renal cell carcinoma: report of a case].

Authors:
Xiu-zhen Wu

Zhonghua Bing Li Xue Za Zhi 2013 Sep;42(9):622-3

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September 2013

[Comparison of two gastric cancer screening schemes in a high-risk population].

Zhonghua Zhong Liu Za Zhi 2013 May;35(5):394-7

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142,China.

Objective: To evaluate the effects of two gastric cancer screening schemes for early detection of gastric cancer in a high-risk population.

Methods: A cluster random sampling method was used to select local residents aged 40-69 years from Linqu County, Shandong Province. "Serum pepsinogen initial screening combined with further endoscopic examination (PG scheme)" and "direct endoscopic examination (endoscopy scheme)" were conducted. The associations between screening schemes and detection rates of gastric cancer, and early gastric cancer/high-grade intraepithelial neoplasia were evaluated by unconditional logistic regression analysis.

Results: Overall, 3654 and 2290 participants completed PG and endoscopy schemes, respectively. A total of 11 (0.30%) cases of gastric cancer and 10 (0.27%) cases of high-grade intraepithelial neoplasia were detected by PG scheme, of which 7 (0.19%) cases were early gastric cancer. While, 19 (0.83%) cases of gastric cancer and 10 (0.44%) cases of high-grade intraepithelial neoplasia were detected by endoscopy scheme, with 12 (0.52%) cases of early gastric cancer. Compared with the PG scheme, the endoscopy scheme had a significantly higher detection rates of gastric cancer (OR = 2.83, 95%CI 1.34-5.98), and early gastric cancer/high-grade intraepithelial neoplasia (OR = 2.12, 95%CI 1.12-4.02).

Conclusions: The endoscopy scheme is more effective in the detection of gastric cancer in a high-risk population, particularly for early gastric cancer/high-grade intraepithelial neoplasia than the PG scheme.
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http://dx.doi.org/10.3760/cma.j.issn.0253-3766.2013.05.016DOI Listing
May 2013

[Longitudinal surveillance of intestinal nematodiasis in Yinghu Village of Wujiang City].

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2012 Aug;24(4):497-8

Wujiang Municipal Center for Disease Control and Prevention, Jiangsu Province, Wujiang 215200, China.

Objective: To understand the epidemic dynamics of intestinal nematodiasis in Wujiang City.

Method: The residents of Yinghu Village of Wujiang City were investigated with Kato-Katz technique for the infections of intestinal nematodes, and the persons with the infections were administered with anthelmintics and they also received the health education.

Results: Of the 5 757 residents, 147 persons were infected with intestinal nematodes, with the average infection rate of 2.55%. The infection rates of hookworm, Ascaris lumbricoides and Tricuris trichiura were 1.96%, 0.49% and 0.24%, respectively. The repeated infection rate was 20.30%, that was 10.36 times higher than the new infection rate (1.96%).

Conclusions: There are still regions and populations with high infection rates of intestinal nematodes in Wujiang City where the intestinal nematodiasis has been controlled. Therefore, it is necessary to strengthen the monitoring, prevention and control work.
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August 2012

Retigeric acid B exerts antifungal effect through enhanced reactive oxygen species and decreased cAMP.

Biochim Biophys Acta 2011 May 21;1810(5):569-76. Epub 2011 Feb 21.

Department of Natural Product Chemistry, Shandong University, Jinan, People's Republic of China.

Background: Retigeric acid B (RAB), a triterpene acid isolated from Lobaria kurokawae exerts antifungal effect. The present study was designed to elucidate the underlying mechanisms by which RAB regulates the proliferation and cell death of Candida albicans.

Methods: We measured the metabolic activity of C. albicans with WST1 Cell Proliferation and Cytotoxicity Assay Kit, analyzed the cell cycle by flow cytometry, visualized the ultrastructure by transmission electron microscopy (TEM) and investigated the apoptosis and necrosis induced by RAB using confocal microscopy. The reactive oxygen species (ROS) accumulation was determined by spectrophotometry, flow cytometry and fluorescent microscopy. The mtΔψ was detected using flow cytometry. And the levels of intracellular cAMP and ATP were measured with cAMP ELISA and ATP Assay Kits, respectively.

Results: The proliferation of the yeasts was blocked in G(2)/M phase by a low dose of RAB treatment and in G(1) phase at high concentration. When cultured in phosphate buffered saline (PBS) deprived of energy source, yeasts displayed the phenotype of death caused by accumulated ROS, mtΔψ hyperpolarization and dramatic decrease in ATP level in the presence of high dose of RAB.

General Significance: RAB inhibits the growth of C. albicans by stimulating ROS production and reducing intracellular cAMP. The ROS accumulation, mtΔψ hyperpolarization, ATP depletion and damaged plasma membrane integrity together mediate cell death of C. albicans induced by RAB. Our findings provide a novel molecular mechanism for exploring possible applications of lichen derived metabolites in fighting fungal infection in humans.
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http://dx.doi.org/10.1016/j.bbagen.2011.02.001DOI Listing
May 2011

Antifungal macrocyclic bis(bibenzyls) from the Chinese liverwort Ptagiochasm intermedlum L.

Nat Prod Res 2010 Apr;24(6):515-20

School of Pharmaceutical Sciences, Shandong University, Jinan, PR China.

Six macrocyclic bis(bibenzyls) were obtained from the Chinese liverwort Ptagiochasm intermedlum L., and their structures were elucidated as pakyonol (1), neomarchantin A (2), isoriccardin C (3), marchantin H (4), riccardin F (5) and riccardin C (6) on the basis of spectroscopic data and comparison with known compounds. Among them, compounds 3-5 were isolated from this liverwort species for the first time. They possessed in vitro antifungal properties against the fluconazole-sensitive and resistant strains of Candida albicans, with minimum inhibitory concentrations (MICs) ranging from 32 to >512 microg mL(-1). Furthermore, riccardin C was also demonstrated to act as a fungal resistance modifying agent when its combined effect with fluconazole on three resistant strains of C. albicans was investigated. The synergistic or additive activity of riccardin C caused dramatically reduced MICs of fluconazole by at most 256-fold.
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http://dx.doi.org/10.1080/14786410802271587DOI Listing
April 2010

Plagiochin E, an antifungal active macrocyclic bis(bibenzyl), induced apoptosis in Candida albicans through a metacaspase-dependent apoptotic pathway.

Biochim Biophys Acta 2010 Apr 11;1800(4):439-47. Epub 2010 Jan 11.

Department of Natural Products Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan 250012, PR China.

Background: Plagiochin E (PLE) is an antifungal active macrocyclic bis(bibenzyl) isolated from liverwort Marchantia polymorpha L. To elucidate the mechanism of action, previous studies revealed that the antifungal effect of PLE was associated with the accumulation of ROS, an important regulator of apoptosis in Candida albicans. The present study was designed to find whether PLE caused apoptosis in C. albicans.

Methods: We assayed the cell cycle by flow cytometry using PI staining, observed the ultrastructure by transmission electron microscopy, studied the nuclear fragmentation by DAPI staining, and investigated the exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane by the FITC-annexin V staining. The effect of PLE on expression of CDC28, CLB2, and CLB4 was determined by RT-PCR. Besides, the activity of metacaspase was detected by FITC-VAD-FMK staining, and the release of cytochrome c from mitochondria was also determined. Furthermore, the effect of antioxidant L-cysteine on PLE-induced apoptosis in C. albicans was also investigated.

Results: Cells treated with PLE showed typical markers of apoptosis: G(2)/M cell cycle arrest, chromatin condensation, nuclear fragmentation, and phosphatidylserine exposure. The expression of CDC28, CLB2, and CLB4 was down-regulated by PLE, which may contribute to PLE-induced G(2)/M cell cycle arrest. Besides, PLE promoted the cytochrome c release and activated the metacaspase, which resulted in the yeast apoptosis. The addition of L-cysteine prevented PLE-induced nuclear fragmentation, phosphatidylserine exposure, and metacaspase activation, indicating the ROS was an important mediator of PLE-induced apoptosis.

Conclusions: PLE induced apoptosis in C. albicans through a metacaspase-dependent apoptotic pathway.

General Significance: In this study, we reported for the first time that PLE induced apoptosis in C. albicans through activating the metacaspase. These results would conduce to elucidate its underlying antifungal mechanism.
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http://dx.doi.org/10.1016/j.bbagen.2010.01.001DOI Listing
April 2010

Plagiochin E, an antifungal bis(bibenzyl), exerts its antifungal activity through mitochondrial dysfunction-induced reactive oxygen species accumulation in Candida albicans.

Biochim Biophys Acta 2009 Aug 13;1790(8):770-7. Epub 2009 May 13.

School of Pharmaceutical Sciences, Shandong University, No. 44 West Wenhua Road, Jinan 250012, PR China.

Background: Plagiochin E (PLE) is an antifungal macrocyclic bis(bibenzyl) isolated from liverwort Marchantia polymorpha L. Its antifungal mechanism is unknown. To elucidate the mechanism of action, its effect on mitochondria function in Candida albicans was studied.

Methods: We assayed the mitochondrial membrane potential (mtDeltapsi) using rhodamine 123, measured ATP level in mitochondria by HPLC, and detected the activities of mitochondrial F(0)F(1)-ATPase and dehydrogenases. Besides, the mitochondrial dysfunction-induced reactive oxygen species (ROS) production was determined by a fluorometric assay, and the effects of antioxidant L-cysteine on PLE-induced ROS production and the antifungal effect of PLE on C. albicans were also investigated.

Results: Exposure to PLE resulted in an elevation of mtDeltapsi, and a decrease of ATP level in mitochondria. The ATP depletion owed to PLE-induced enhancement of mitochondrial F(0)F(1)-ATPase and inhibition of the mitochondrial dehydrogenases. These dysfunctions of mitochondria caused ROS accumulation in C. albicans, and this increase in the level of ROS production and PLE-induced decrease in cell viability were prevented by addition of L-cysteine, indicating that ROS was an important mediator of the antifungal action of PLE.

Conclusions: PLE exerts its antifungal activity through mitochondrial dysfunction-induced ROS accumulation in C. albicans.

General Significance: The effect of PLE on the mitochondria function in C. albicans was assayed for the first time. These results would conduce to elucidate its underlying antifungal mechanism.
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http://dx.doi.org/10.1016/j.bbagen.2009.05.002DOI Listing
August 2009

The effect of plagiochin E alone and in combination with fluconazole on the ergosterol biosynthesis of Candida albicans.

Biol Pharm Bull 2009 Jan;32(1):36-40

School of Pharmaceutical Sciences, Shandong University, Jinan, PR China.

Plagiochin E (PLE), a macrocyclic bis(bibenzyl) isolated from the liverwort Marchantia polymorpha, has been reported to have antifungal activity and resistance reversal effects on Candida albicans. In order to understand the underlying mechanisms, we studied the effects of PLE alone and in combination with fluconazole (FLC) on the ergosterol biosynthetic pathway against both FLC-sensitive and FLC-resistant strains by analyzing the sterol content and the ergosterol pathway gene (ERG) expression. Relative quantitative analysis of different ergosterol precursors was carried out by employing the hyphenated technique of gas chromatography-high resolution mass spectrometry (GC-HR-MS). We observed that for FLC-resistant strain PLE itself can cause the accumulation of lanosterol and the decrease of 14alpha-methylfecosterol. When it combined with FLC, a significant decrease was observed in ergosterol formation and corresponding accumulation of 14alpha-methylated sterols was also found. Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that the transcription level of ERG11 was decreased in FLC-resistant strain when exposed to PLE alone or PLE plus FLC. These results suggest that PLE potentiates FLC antifungal activity by interfering with the FLC-targeted ergosterol biosynthesis pathway.
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http://dx.doi.org/10.1248/bpb.32.36DOI Listing
January 2009

Effect of plagiochin E, an antifungal macrocyclic bis(bibenzyl), on cell wall chitin synthesis in Candida albicans.

Acta Pharmacol Sin 2008 Dec;29(12):1478-85

School of Pharmaceutical Sciences, Shandong University, Ji-nan 250012, China.

Aim: To investigate the effect of plagiochin E (PLE), an antifungal macrocyclic bis(bibenzyl) isolated from liverwort Marchantia polymorpha L, on cell wall chitin synthesis in Candida albicans.

Methods: The effect of PLE on chitin synthesis in Candida albicans was investigated at the cellular and molecular levels. First, the ultrastructural changes were observed under transmission electron microscopy (TEM). Second, the effects of PLE on chitin synthetase (Chs) activities in vitro were assayed using 6-O-dansyl-N-acetylglucosamine as a fluorescent substrate, and its effect on chitin synthesis in situ was assayed by spheroplast regeneration. Finally, real-time RT-PCR was performed to assay its effect on the expression of Chs genes (CHS).

Results: Observation under TEM showed that the structure of the cell wall in Candida albicans was seriously damaged, which suggested that the antifungal activity of PLE was associated with its effect on the cell wall. Enzymatic assays and spheroplast regeneration showed that PLE inhibited chitin synthesis in vitro and in situ. The results of the PCR showed that PLE significantly downregulated the expression of CHS1, and upregulated the expression of CHS2 and CHS3. Because different Chs is regulated at different stages of transcription and post-translation, the downregulation of CHS1 would decrease the level of Chs1 and inhibit its activity, and the inhibitory effects of PLE on Chs2 and Chs3 would be at the post-translational level or by the inhibition on the enzyme-active center.

Conclusion: These results indicate that the antifungal activity of PLE would be attributed to its inhibitory effect on cell wall chitin synthesis in Candida albicans.
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http://dx.doi.org/10.1111/j.1745-7254.2008.00900.xDOI Listing
December 2008
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