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11. Transmission of bla NDM in Enterobacteriaceae among animals, food and human

Author

Fu, Bo, primary, Xu, Jian, additional, Yin, Dandan, additional, Sun, Chengtao, additional, Liu, Dejun, additional, Zhai, Weishuai, additional, Bai, Rina, additional, Cao, Yue, additional, Zhang, Qin, additional, Ma, Shizhen, additional, Walsh, Timothy R., additional, Hu, Fupin, additional, Wang, Yang, additional, Wu, Congming, additional, and Shen, Jianzhong, additional

Published
2024
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17. Comparative Efficacy of Anaerobic Digestion Systems in Removing Antimicrobial Resistance Genes from Swine Wastewater

Author

Sun, Da, primary, Shi, Xiaomin, additional, Shen, Yingbo, additional, Liu, Ying, additional, Luo, Sunlin, additional, Jin, Yongpeng, additional, Zhai, Weishuai, additional, Liu, Lu, additional, Deng, Zhaoju, additional, Sun, Chengtao, additional, Liu, Dejun, additional, Yang, Xin, additional, Xie, Youzhi, additional, Krüger-Haker, Henrike, additional, Wu, Congming, additional, Schwarz, Stefan, additional, Shen, Jianzhong, additional, Chen, Yiqiang, additional, and Wang, Yang, additional

Published
2024
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22. Tigecycline Sensitivity Reduction in Escherichia coli Due to Widely Distributed tet (A) Variants.

Author

Zhang, Shan, Cui, Mingquan, Liu, Dejun, Fu, Bo, Shi, Tingxuan, Wang, Yang, Sun, Chengtao, and Wu, Congming

Subjects
ESCHERICHIA coli, TIGECYCLINE, GENOMICS, GENE expression, FOOD of animal origin, SWINE breeding, SWINE farms
Abstract

Despite scattered studies that have reported mutations in the tet(A) gene potentially linked to tigecycline resistance in clinical pathogens, the detailed function and epidemiology of these tet(A) variants remains limited. In this study, we analyzed 64 Escherichia coli isolates derived from MacConkey plates supplemented with tigecycline (2 μg/mL) and identified five distinct tet(A) variants that account for reduced sensitivity to tigecycline. In contrast to varied tigecycline MICs (0.25 to 16 μg/mL) of the 64 tet(A)-variant-positive E. coli isolates, gene function analysis confirmed that the five tet(A) variants exhibited a similar capacity to reduce tigecycline sensitivity in DH5α carrying pUC19. Among the observed seven non-synonymous mutations, the V55M mutation was unequivocally validated for its positive role in conferring tigecycline resistance. Interestingly, the variability in tigecycline MICs among the E. coli strains did not correlate with tet(A) gene expression. Instead, a statistically significant reduction in intracellular tigecycline concentrations was noted in strains displaying higher MICs. Genomic analysis of 30 representative E. coli isolates revealed that tet(A) variants predominantly resided on plasmids (n = 14) and circular intermediates (n = 13). Within China, analysis of a well-characterized E. coli collection isolated from pigs and chickens in 2018 revealed the presence of eight tet(A) variants in 103 (4.2%, 95% CI: 3.4–5.0%) isolates across 13 out of 17 tested Chinese provinces or municipalities. Globally, BLASTN analysis identified 21 tet(A) variants in approximately 20.19% (49,423/244,764) of E. coli genomes in the Pathogen Detection database. These mutant tet(A) genes have been widely disseminated among E. coli isolates from humans, food animals, and the environment sectors, exhibiting a growing trend in tet(A) variants over five decades. Our findings underscore the urgency of addressing tigecycline resistance and the underestimated role of tet(A) mutations in this context. [ABSTRACT FROM AUTHOR]

Published
2023
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23. Spreading of cfr -Carrying Plasmids among Staphylococci from Humans and Animals

Author

Gao, Yuan, primary, Wang, Zheng, additional, Fu, Jiani, additional, Cai, Jiachang, additional, Ma, Tengfei, additional, Xie, Ning, additional, Fan, Run, additional, Zhai, Weishuai, additional, Feßler, Andrea T., additional, Sun, Chengtao, additional, Wu, Congming, additional, Schwarz, Stefan, additional, Zhang, Rong, additional, and Wang, Yang, additional

Published
2022
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26. Inhibition of mitochondrial translocase SLC25A5 and histone deacetylation is an effective combination therapy in neuroblastoma

Author

Seneviratne, Janith A., primary, Carter, Daniel R., additional, Mittra, Rituparna, additional, Gifford, Andrew, additional, Kim, Patrick Y., additional, Luo, Jie‐Si, additional, Mayoh, Chelsea, additional, Salib, Alice, additional, Rahmanto, Aldwin S., additional, Murray, Jayne, additional, Cheng, Ngan C., additional, Nagy, Zsuzsanna, additional, Wang, Qian, additional, Kleynhans, Ane, additional, Tan, Owen, additional, Sutton, Selina K., additional, Xue, Chengyuan, additional, Chung, Sylvia A., additional, Zhang, Yizhuo, additional, Sun, Chengtao, additional, Zhang, Li, additional, Haber, Michelle, additional, Norris, Murray D., additional, Fletcher, Jamie I., additional, Liu, Tao, additional, Dilda, Pierre J., additional, Hogg, Philip J., additional, Cheung, Belamy B., additional, and Marshall, Glenn M., additional

Published
2022
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29. Total flavonoids from the dried root of Tetrastigma hemsleyanum Diels et Gilg inhibit colorectal cancer growth through PI3K/AKT/mTOR signaling pathway

Author

Zhai, Yufei, primary, Sun, Jing, additional, Sun, Chengtao, additional, Zhao, Huan, additional, Li, Xuan, additional, Yao, Jiaxiong, additional, Su, Jiajia, additional, Xu, Xiaoqian, additional, Xu, Xiukun, additional, Hu, Jiangning, additional, Daglia, Maria, additional, Han, Bing, additional, and Kai, Guoyin, additional

Published
2022
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30. Inter-host Transmission of Carbapenemase-Producing Escherichia coli among Humans and Backyard Animals

Author

Li, Jiyun, Bi, Zhenwang, Ma, Shizhen, Chen, Baoli, Cai, Chang, He, Junjia, Schwarz, Stefan, Sun, Chengtao, Zhou, Yuqing, Yin, Jia, Hulth, Anette, Wang, Yongqiang, Shen, Zhangqi, Wang, Shaolin, Wu, Congming, Nilsson, Lennart E., Walsh, Timothy R., Borjesson, Stefan, Shen, Jianzhong, Sun, Qiang, and Wang, Yang

Subjects
United States. Centers for Disease Control and Prevention, Disease transmission -- Health aspects, Imipenem -- Health aspects, Medical research -- Health aspects, Genetic polymorphisms -- Health aspects, Genomics -- Health aspects, Escherichia coli -- Health aspects, Meropenem -- Health aspects, Swine -- Health aspects, Beef cattle, Motor vehicle drivers, Public health, DNA sequencing, Single nucleotide polymorphisms, Genomes, Fertilizers, Public health movements, Environmental issues, Health
Abstract

Background: The rapidly increasing dissemination of carbapenem-resistant Enterobacteriaceae (CRE) in both humans and animals poses a global threat to public health. However, the transmission of CRE between humans and animals has not yet been well studied. Objectives: We investigated the prevalence, risk factors, and drivers of CRE transmission between humans and their backyard animals in rural China. Methods: We conducted a comprehensive sampling strategy in 12 villages in Shandong, China. Using the household [residents and their backyard animals (farm and companion animals)] as a single surveillance unit, we assessed the prevalence of CRE at the household level and examined the factors associated with CRE carriage through a detailed questionnaire. Genetic relationships among human- and animal-derived CRE were assessed using whole-genome sequencing-based molecular methods. Results: A total of 88 New Delhi metallo-[beta]-lactamases-type carbapenem-resistant Escherichia coli (NDM-EC), including 17 from humans, 44 from pigs, 12 from chickens, 1 from cattle, and 2 from dogs, were isolated from 65 of the 746 households examined. The remaining 12 NDM-EC were from flies in the immediate backyard environment. The NDM-EC colonization in households was significantly associated with a) the number of species of backyard animals raised/kept in the same household, and b) the use of human and/or animal feces as fertilizer. Discriminant analysis of principal components (DAPC) revealed that a large proportion of the core genomes of the NDM-EC belonged to strains from hosts other than their own, and several human isolates shared closely related core single-nucleotide polymorphisms and [bla.sub.NDM] genetic contexts with isolates from backyard animals. Conclusions: To our knowledge, we are the first to report evidence of direct transmission of NDM-EC between humans and animals. Given the rise of NDM-EC in community and hospital infections, combating NDM-EC transmission in backyard farm systems is needed. https://doi.org/10.1289/EHP5251, Introduction Carbapenems, particularly imipenem, meropenem, and ertapenem, play a vital role in the treatment of human clinical infections caused by multidrug-resistant (MDR) Gram-negative bacteria (Nordmann et al. 2012). Carbapenems are [...]

Published
2019
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31. Inhibition of mitochondrial translocase SLC25A5 and histone deacetylation is an effective combination therapy in neuroblastoma.

Author

Seneviratne, Janith A., Carter, Daniel R., Mittra, Rituparna, Gifford, Andrew, Kim, Patrick Y., Luo, Jie‐Si, Mayoh, Chelsea, Salib, Alice, Rahmanto, Aldwin S., Murray, Jayne, Cheng, Ngan C., Nagy, Zsuzsanna, Wang, Qian, Kleynhans, Ane, Tan, Owen, Sutton, Selina K., Xue, Chengyuan, Chung, Sylvia A., Zhang, Yizhuo, and Sun, Chengtao

Subjects
NEUROBLASTOMA, HISTONE deacetylase inhibitors, DEACETYLATION, CHILDHOOD cancer, MITOCHONDRIAL proteins, HISTONE deacetylase
Abstract

The mitochondrion is a gatekeeper of apoptotic processes, and mediates drug resistance to several chemotherapy agents used to treat cancer. Neuroblastoma is a common solid cancer in young children with poor clinical outcomes following conventional chemotherapy. We sought druggable mitochondrial protein targets in neuroblastoma cells. Among mitochondria‐associated gene targets, we found that high expression of the mitochondrial adenine nucleotide translocase 2 (SLC25A5/ANT2), was a strong predictor of poor neuroblastoma patient prognosis and contributed to a more malignant phenotype in pre‐clinical models. Inhibiting this transporter with PENAO reduced cell viability in a panel of neuroblastoma cell lines in a TP53‐status‐dependant manner. We identified the histone deacetylase inhibitor, suberanilohydroxamic acid (SAHA), as the most effective drug in clinical use against mutant TP53 neuroblastoma cells. SAHA and PENAO synergistically reduced cell viability, and induced apoptosis, in neuroblastoma cells independent of TP53‐status. The SAHA and PENAO drug combination significantly delayed tumour progression in pre‐clinical neuroblastoma mouse models, suggesting that these clinically advanced inhibitors may be effective in treating the disease. [ABSTRACT FROM AUTHOR]

Published
2023
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35. Prevalence, transmission, and molecular epidemiology of tet(X)-positive bacteria among humans, animals, and environmental niches in China: An epidemiological, and genomic-based study

Author

Dong, Ning, primary, Zeng, Yu, additional, Cai, Chang, additional, Sun, Chengtao, additional, Lu, Jiayue, additional, Liu, Congcong, additional, Zhou, Hongwei, additional, Sun, Qiaoling, additional, Shu, Lingbin, additional, Wang, Hanyu, additional, Wang, Yang, additional, Wang, Shaoling, additional, Wu, Congming, additional, Chan, Edward Wai-Chi, additional, Chen, Gongxiang, additional, Shen, Zhangqi, additional, Chen, Sheng, additional, and Zhang, Rong, additional

Published
2022
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36. Bioinformatics Analysis and Validation Identify CDK1 and MAD2L1 as Prognostic Markers of Rhabdomyosarcoma

Author

Lu, Suying, Sun, Chengtao, Chen, Huimou, Zhang, Chao, Li, Wei, Wu, Liuhong, Zhu, Jia, Sun, Feifei, Huang, Junting, Wang, Juan, Zhen, Zijun, Cai, Ruiqing, Sun, Xiaofei, Zhang, Yizhuo, and Zhang, Xing

Subjects
MAD2L1, CDK1, Cancer Management and Research, rhabdomyosarcoma, prognosis, TCGA, GEO, Original Research
Abstract

Suying Lu,1,2,* Chengtao Sun,3,* Huimou Chen,1,2,* Chao Zhang,1,4,* Wei Li,5 Liuhong Wu,1,2 Jia Zhu,1,2 Feifei Sun,1,2 Junting Huang,1,2 Juan Wang,1,2 Zijun Zhen,1,2 Ruiqing Cai,1,2 Xiaofei Sun,1,2 Yizhuo Zhang,1,2 Xing Zhang1,6 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, People’s Republic of China; 2Department of Pediatric Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 3Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of China; 4Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China; 5Department of Cardiology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 6Department of Medical Melanoma and Sarcoma, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing ZhangDepartment of Medical Melanoma and Sarcoma, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Guangzhou, Guangdong 510060, People’s Republic of ChinaTel/Fax +86-020-87343629Email zhangxing@sysucc.org.cnYizhuo Zhang Department of Pediatric OncologySun Yat-sen University Cancer Center, 651 East Dongfeng Road, Guangzhou, Guangdong 510060, People’s Republic of ChinaTel/Fax +86-020-87342458Email zhangyzh@sysucc.org.cnPurpose: The goal of the current study was to identify potential prognostic biomarkers of rhabdomyosarcoma (RMS).Materials and Methods: We screened chip sequencing datasets of RMS through the gene expression omnibus (GEO) database. A total of 74 RMS patient tissues and 39 normal muscle cell tissues were analyzed. Limma R software was used to identify the differentially expressed genes (DEGs) between RMS tissues and normal controls. The GO plot R package was used to visualize the results of the GO analysis. We screened for pathaffy package enrichment of DEGs by the Kyoto Encyclopedia of Genes and Genomes (KEGG). The cutoff criterion was a P-value < 0.05. Immunohistochemistry (IHC) was applied to validate the expression of CDK1 (cyclin-dependent kinases 1) and MAD2L1 (Mitotic Arrest Deficient 2 Like 1) in RMS.Results: We obtained a total of 498 up- and 480 down-regulated DEGs. The hub genes are mainly involved in the cell cycle and P53 singling pathway. CDK1 expression was associated with tumor size and COG-STS (Children’s Oncology Group-soft tissue sarcoma) staging of RMS. For the low CDK1 expression group and high CDK1 expression group, the 5-year overall survival (OS) rate was 83.0% vs 63.5% (P = 0.004), and the 5-year event-free survival (EFS) rate was 47.5% vs 27.5% (P = 0.049) respectively. When compared low MAD2L1 expression group with high MAD2L1 expression group, the 5-year OS rate was 80.0% vs 43.2% (P = 0.001), and the 5-year EFS rate was 45.1% vs 21.8% (P = 0.038), respectively. If patients were divided into three groups: low CDK1 and low MAD2L1 expression group, high CDK1 or high MAD2L1 expression group, and high CDK1 and high MAD2L1 expression group, the 5-year OS rate was 87.1%, 58.6%, 39.6% (P = 0.001), while the 5-year EFS rate of RMS patients was 54.2%, 23.2%, 21.7% (P = 0.028), respectively.Conclusion: This study has identified that CDK1 and MAD2L1 were adverse prognostic factors of RMS.Keywords: rhabdomyosarcoma, GEO, TCGA, CDK1, MAD2L1, prognosis

Published
2020

41. Fecal Carriage of Escherichia coli Harboring the tet (X4)-IncX1 Plasmid from a Tertiary Class-A Hospital in Beijing, China.

Author

Zhai, Weishuai, Tian, Yingxin, Shao, Dongyan, Zhang, Muchen, Li, Jiyun, Song, Huangwei, Sun, Chengtao, Wang, Yang, Liu, Dejun, and Zhang, Ying

Subjects
ESCHERICHIA coli, HORIZONTAL gene transfer, TIGECYCLINE, POLYMYXIN, MEROPENEM, KLEBSIELLA pneumoniae, BABESIA
Abstract

The emergence of the mobile tigecycline-resistance gene, tet(X4), poses a significant threat to public health. To investigate the prevalence and genetic characteristics of the tet(X4)-positive Escherichia coli in humans, 1101 human stool samples were collected from a tertiary class-A hospital in Beijing, China, in 2019. Eight E. coli isolates that were positive for tet(X4) were identified from clinical departments of oncology (n = 3), hepatology (n = 2), nephrology (n = 1), urology (n = 1), and general surgery (n = 1). They exhibited resistance to multiple antibiotics, including tigecycline, but remained susceptible to meropenem and polymyxin B. A phylogenetic analysis revealed that the clonal spread of four tet(X4)-positive E. coli from different periods of time or departments existed in this hospital, and three isolates were phylogenetically close to the tet(X4)-positive E. coli from animals and the environment. All tet(X4)-positive E. coli isolates contained the IncX1-plasmid replicon. Three isolates successfully transferred their tigecycline resistance to the recipient strain, C600, demonstrating that the plasmid-mediated horizontal gene transfer constitutes another critical mechanism for transmitting tet(X4). Notably, all tet(X4)-bearing plasmids identified in this study had a high similarity to several plasmids recovered from animal-derived strains. Our findings revealed the importance of both the clonal spread and horizontal gene transfer in the spread of tet(X4) within human clinics and between different sources. [ABSTRACT FROM AUTHOR]

Published
2022
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42. MDM2-P53 Signaling Pathway-Mediated Upregulation of CDC20 Promotes Progression of Human Diffuse Large B-Cell Lymphoma

Author

Sun,Chengtao, Li,Mengzhen, Feng,Yanfen, Sun,Feifei, Zhang,Li, Xu,Yanjie, Lu,Suying, Zhu,Jia, Huang,Junting, Wang,Juan, Hu,Yang, and Zhang,Yizhuo

Subjects
OncoTargets and Therapy
Abstract

Chengtao Sun,1,* Mengzhen Li,1,* Yanfen Feng,2,3,* Feifei Sun,2,4 Li Zhang,2,4 Yanjie Xu,1 Suying Lu,2,4 Jia Zhu,2,4 Junting Huang,2,4 Juan Wang,2,4 Yang Hu,1 Yizhuo Zhang1,2,4 1Department of Hematology, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, People’s Republic of China; 4Department of Pediatric Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yizhuo Zhang Tel/ Fax +86-20-87343799Email yizhuozhang111@163.comBackground: Cell-division cycle 20 (CDC20) is overexpressed in a variety of tumor cells and is negatively regulated by wild-type p53 (wtp53). Our previous study uncovered that CDC20 was upregulated and associated with poor outcome in diffuse large B-cell lymphoma (DLBCL) based on bioinformatics analysis. Dysregulation of the MDM2-p53 is a major mechanism to promote DLBCL. Thus, we hypothesized that CDC20 could be a downstream gene of the MDM2-p53 signaling pathway. However, the clinical significance and mechanistic role of a novel MDM2-p53-CDC20 signaling pathway in DLBCL have still remained unclear.Materials and Methods: RT-qPCR was performed in MDM2 knocked down (KD) and control (Ctrl) OCI-Ly3/OCI-Ly10 cells to investigate whether CDC20 was a downstream gene of the MDM2-p53 pathway. The effects of CDC20 on cell proliferation, cell cycle and apoptosis were assessed, as well as the role of CDC20 in suppressing tumorigenicity in vivo. Furthermore, we also investigated the roles of CDC20 and MDM2 in progression of DLBCL and the underlying mechanisms.Results: The results of RT-qPCR revealed that CDC20 was downregulated while TP53 was upregulated in MDM2 KD OCI-Ly3 and OCI-Ly10 cells. It was unveiled that the expression levels of CDC20 and MDM2 were upregulated in DLBCL tissues and cells, and high CDC20 expression was correlated with adverse clinical features and poor outcome. Functional assays showed that downregulation of CDC20 could inhibit proliferation, induce apoptosis and cell cycle arrest in vitro. In addition, inactivation of the MDM2-p53 pathway by downregulation of MDM2 restored wtp53 expression level and reduced CDC20 protein level in OCI-Ly3 and OCI-Ly10 cells. Besides, targeting CDC20 was found to suppress tumorigenesis of DLBCL in vivo.Conclusion: CDC20 was identified as a key downstream gene of the MDM2-p53 signaling pathway in DLBCL and may be used as a novel target gene to guide therapeutic applications.Keywords: DLBCL, MDM2-p53 signaling pathway, CDC20, tumor progression

Published
2020

43. Novel Insight into Utilization of Flavonoid Glycosides and Biological Properties of Saffron (Crocus sativus L.) Flower Byproducts

Author

Sun, Chengtao, Nile, Shivraj Hariram, Zhang, Yiting, Qin, Luping, El-Seedi, Hesham, Daglia, Maria, Kai, Guoyin, Sun, Chengtao, Nile, Shivraj Hariram, Zhang, Yiting, Qin, Luping, El-Seedi, Hesham, Daglia, Maria, and Kai, Guoyin

Abstract

Saffron (Crocus sativus L.) byproducts are considered as a cheap source of bioactive polyphenolics endowed with potential antioxidant effects. The saffron biowaste is utilized for extraction of flavonoid glycosides and their potential biological properties. The total amount of polyphenolics and polysaccharides was found to be higher in the tepal than in the stamen. The bioactive compounds quercetin-3-O-sophoroside (Q-3-sop) and kaempferol-3-O-sophoroside (K-3-sop) were analyzed using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA) and identified by high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR). The antioxidant effects were studied using 2,2 diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), ferric ion reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC); Q-3-sop showed stronger antioxidant effects compared to K-3-sop, crocin-I, and crocin-II. Furthermore, Q-3-sop also inhibited cell apoptosis caused by H2O2 by reducing the levels of cellular reactive oxygen species (ROS). In terms of cytogenetic effects, Q-3-sop revealed no cytogenic effects on onion root meristem cells but chromosomal aberration was observed at the highest dose (200 ppm). Thus, saffron byproducts and its flavonoids could be utilized as natural antioxidant agents with no cytogenetic effects.

Published
2020
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44. The Effectiveness of an Educational Intervention on Knowledge, Attitudes and Reported Practices on Antibiotic Use in Humans and Pigs: A Quasi-Experimental Study in Twelve Villages in Shandong Province, China

Author

Shen, Liyan, primary, James Dyar, Oliver, additional, Sun, Qiang, additional, Wei, Xiaolin, additional, Yang, Ding, additional, Sun, Chengtao, additional, Wang, Yang, additional, Li, Hongyu, additional, Liu, Yuqing, additional, Luo, Yanbo, additional, Yin, Jia, additional, and Stålsby Lundborg, Cecilia, additional

Published
2021
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