Browsing by Author "Liu, Shu-Lin"

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    Association of Salmonella virulence factor alleles with intestinal and invasive serovars
    (2019-05-28) Rakov, Alexey V; Mastriani, Emilio; Liu, Shu-Lin; Schifferli, Dieter M
    Abstract Background The role of Salmonella virulence factor (VF) allelic variation in modulating pathogenesis or host specificity has only been demonstrated in a few cases, mostly through serendipitous findings. Virulence factor (VF) alleles from Salmonella enterica subsp. enterica genomes were compared to identify potential associations with the host-adapted invasive serovars Typhi, Dublin, Choleraesuis, and Gallinarum, and with the broad host-range intestinal serovars Typhimurium, Enteritidis, and Newport. Results Through a bioinformatics analysis of 500 Salmonella genomes, we have identified allelic variants of 70 VFs, many of which are associated with either one of the four host-adapted invasive Salmonella serovars or one of the three broad host-range intestinal serovars. In addition, associations between specific VF alleles and intra-serovar clusters, sequence types (STs) and/or host-adapted FimH adhesins were identified. Moreover, new allelic VF associations with non-typhoidal S. Enteritidis and S. Typhimurium (NTS) or invasive NTS (iNTS) were detected. Conclusions By analogy to the previously shown association of specific FimH adhesin alleles with optimal binding by host adapted Salmonella serovars, lineages or strains, we predict that some of the identified association of other VF alleles with host-adapted serovars, lineages or strains will reflect specific contributions to host adaptation and/or pathogenesis. The identification of these allelic associations will support investigations of the biological impact of VF alleles and better characterize the role of allelic variation in Salmonella pathogenesis. Most relevant functional experiments will test the potential causal contribution of the detected FimH-associated VF variants in host adapted virulence.
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    Associations of CXCL1 gene 5’UTR variations with ovarian cancer
    (2020-04-23) Guo, Man; Xu, Chao; Chen, Yan-Zhe; Sun, Qi-Wen; Zhao, Xin-Ying; Liu, Xin; Yang, Yi; Hu, Yi-Yan; Li, Fei-Feng; Liu, Shu-Lin
    Abstract Background There are about 2.4 hundred thousand new cases and 1.5 hundred thousand deaths of ovarian cancer (OC) annually in the world. Chronic inflammation is a risk factor for OC. C-X-C motif chemokine ligand 1 (CXCL1) defects may facilitate inflammation and transactivate EGFR in ovarian cancer, but the precise haplotypes associated with the potential diseases remained largely unknown. In this work, we characterized CXCL1 gene variations to elucidate their possible associations with OC. Methods We analyzed the CXCL1 gene for 300 OC patients with 400 healthy participants as controls. The statistical analyses and Hardy-Weinberg equilibrium tests of the patients and control populations were conducted using the SPSS software (version 19.0) and Plink (version 1.9). Results The variants rs11547681, rs201090116, rs199791199, rs181868085, rs4074 and rs1814092 within or near the CXCL1 gene were characterized. The genetic heterozygosity of rs11547681 and rs4074 was very high. Statistical analysis showed that the variant rs11547681 in the gene was closely associated with the risk of OC in the Chinese Han population, although this variant was not associated with FIGO stages or pathological grades of the patients. Conclusions Rs11547681 in CXCL1 gene was associated with the risk of OC in the Chinese Han population.
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    Defining natural species of bacteria: clear-cut genomic boundaries revealed by a turning point in nucleotide sequence divergence
    (BioMed Central, 2013-07-18) Tang, Le; Li, Yang; Deng, Xia; Johnston, Randal N; Liu, Gui-Rong; Liu, Shu-Lin
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    E. coli diversity: low in colorectal cancer
    (2020-04-06) Tang, Le; Zhou, Yu-Jie; Zhu, Songling; Liang, Gong-Da; Zhuang, He; Zhao, Man-Fei; Chang, Xiao-Yun; Li, Hai-Ning; Liu, Zheng; Guo, Zhi-Rong; Liu, Wei-Qiao; He, Xiaoyan; Wang, Chun-Xiao; Zhao, Dan-Dan; Li, Jia-Jing; Mu, Xiao-Qin; Yao, Bing-Qing; Li, Xia; Li, Yong-Guo; Duo, Li-Bo; Wang, Li; Johnston, Randal N; Zhou, Jin; Zhao, Jing-Bo; Liu, Gui-Rong; Liu, Shu-Lin
    Abstract Background Escherichia coli are mostly commensals but also contain pathogenic lineages. It is largely unclear whether the commensal E. coli as the potential origins of pathogenic lineages may consist of monophyletic or polyphyletic populations, elucidation of which is expected to lead to novel insights into the associations of E. coli diversity with human health and diseases. Methods Using genomic sequencing and pulsed field gel electrophoresis (PFGE) techniques, we analyzed E. coli from the intestinal microbiota of three groups of healthy individuals, including preschool children, university students, and seniors of a longevity village, as well as colorectal cancer (CRC) patients, to probe the commensal E. coli populations for their diversity. Results We delineated the 2280 fresh E. coli isolates from 185 subjects into distinct genome types (genotypes) by PFGE. The genomic diversity of the sampled E. coli populations was so high that a given subject may have multiple genotypes of E. coli, with the general diversity within a host going up from preschool children through university students to seniors. Compared to the healthy subjects, the CRC patients had the lowest diversity level among their E. coli isolates. Notably, E. coli isolates from CRC patients could suppress the growth of E. coli bacteria isolated from healthy controls under nutrient-limited culture conditions. Conclusions The coexistence of multiple E. coli lineages in a host may help create and maintain a microbial environment that is beneficial to the host. As such, the low diversity of E. coli bacteria may be associated with unhealthy microenvironment in the intestine and hence facilitate the pathogenesis of diseases such as CRC.
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    Enterolactone has stronger effects than enterodiol on ovarian cancer
    (2017-07-24) Liu, Huidi; Liu, Jianrui; Wang, Siwen; Zeng, Zheng; Li, Ting; Liu, Yongfang; Mastriani, Emilio; Li, Qing-Hai; Bao, Hong-Xia; Zhou, Yu-Jie; Wang, Xiaoyu; Hu, Sijing; Gao, Shan; Qi, Yingying; Shen, Zhihang; Wang, Hongyue; Yu, Miao; Gao, Tingting; Johnston, Randal N; Liu, Shu-Lin
    Abstract Background Ovarian cancer is one of the three leading gynecological malignancies, characterized by insidious growth, highly frequent metastasis, and quick development of drug resistance. As a result, this disease has low 5-year survival rates. Estrogen receptor inhibitors were commonly used for the treatment, but only 7% to 18% of patients respond to anti-estrogen therapies. Therefore, more effective therapies to inhibit estrogen-related tumors are urgently needed. Recently, phytoestrogens, such as lignans with estrogen-like biological activities, have attracted attention for their potential effects in the prevention or treatment of estrogen-related diseases. Enterodiol (END) and enterolactone (ENL) are mammalian lignans, which can reduce the risk of various cancers. However, the effects of END and ENL on ovarian cancer are not adequately documented. Methods We used in vitro assays on the ES-2 cell line to evaluate the inhibiting effects of END and ENL on ovarian cancer cell proliferation, invasion and migration ability and in vivo xenograft experiments on nude mice to validate the anticancer effects of END and ENL. Results The in vitro assays demonstrated that high-dose END and ENL could obviously inhibit ovarian malignant properties, including cancerous proliferation, invasion, and metastasis. Compared to END, ENL behaved in a better time-dose dependent manner on the cancer cells. The in vivo experiments showed that END (1 mg/kg), ENL (1 mg/kg) and ENL (0.1 mg/kg) suppressed tumor markedly, and there were statistically significant differences between the experimental and control groups in tumor weight and volume. Compared to END, which have serious side effects to the animals at high concentration such as 1 mg/kg, ENL had higher anticancer activities and less side effects in the animals than END at the same concentrations, so it would be a better candidate for drug development. Conclusion END and ENL both have potent inhibitory effects on ovarian cancer but ENL possesses a more effective anti-cancer capability and less side effects than END. Findings in this work provide novel insights into ovarian cancer therapeutics with phytoestrogens and encourage their clinical applications.
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    Genetic boundaries delineate the potential human pathogen Salmonella bongori into discrete lineages: divergence and speciation
    (2019-12-04) Wang, Xiaoyu; Zhu, Songling; Zhao, Jian-Hua; Bao, Hong-Xia; Liu, Huidi; Ding, Tie-Min; Liu, Gui-Rong; Li, Yong-Guo; Johnston, Randal N; Cao, Feng-Lin; Tang, Le; Liu, Shu-Lin
    Abstract Background Salmonella bongori infect mainly cold-blooded hosts, but infections by S. bongori in warm-blooded hosts have been reported. We hypothesized that S. bongori might have diverged into distinct phylogenetic lineages, with some being able to infect warm-blooded hosts. Results To inspect the divergence status of S. bongori, we first completely sequenced the parakeet isolate RKS3044 and compared it with other sequenced S. bongori strains. We found that RKS3044 contained a novel T6SS encoded in a pathogenicity island-like structure, in addition to a T6SS encoded in SPI-22, which is common to all S. bongori strains so far reported. This novel T6SS resembled the SPI-19 T6SS of the warm-blooded host infecting Salmonella Subgroup I lineages. Genomic sequence comparisons revealed different genomic sequence amelioration events among the S. bongori strains, including a unique CTAG tetranucleotide degeneration pattern in RKS3044, suggesting non-overlapping gene pools between RKS3044 and other S. bongori lineages/strains leading to their independent accumulation of genomic variations. We further proved the existence of a clear-cut genetic boundary between RKS3044 and the other S. bongori lineages/strains analyzed in this study. Conclusions The warm-blooded host-infecting S. bongori strain RKS3044 has diverged with distinct genomic features from other S. bongori strains, including a novel T6SS encoded in a previously not reported pathogenicity island-like structure and a unique genomic sequence degeneration pattern. These findings alert cautions about the emergence of new pathogens originating from non-pathogenic ancestors by acquiring specific pathogenic traits.
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    KAZN as a diagnostic marker in ovarian cancer: a comprehensive analysis based on microarray, mRNA-sequencing, and methylation data
    (2022-06-16) Zhu, Songling; Bao, Hongxia; Zhang, Meng-Chun; Liu, Huidi; Wang, Yao; Lin, Caiji; Zhao, Xingjuan; Liu, Shu-Lin
    Abstract Background Ovarian cancer (OC) is among the deadliest malignancies in women and the lack of appropriate markers for early diagnosis leads to poor prognosis in most cases. Previous studies have shown that KAZN is involved in multiple biological processes during development, such as cell proliferation, differentiation, and apoptosis, so defects or aberrant expression of KAZN might cause queer cell behaviors such as malignancy. Here we evaluated the KAZN expression and methylation levels for possible use as an early diagnosis marker for OC. Methods We used data from Gene Expression Omnibus (GEO) microarrays, The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) to investigate the correlations between KAZN expression and clinical characteristics of OC by comparing methylation levels of normal and OC samples. The relationships among differentially methylated sites in the KAZN gene, corresponding KAZN mRNA expression levels and prognosis were analyzed. Results KAZN was up-regulated in ovarian epithelial tumors and the expression of KAZN was correlated with the patients’ survival time. KAZN CpG site cg17657618 was positively correlated with the expression of mRNA and the methylation levels were significantly differential between the group of stage “I and II” and the group of stage “III and IV”. This study also presents a new method to classify tumor and normal tissue in OC using DNA methylation pattern in the KAZN gene body region. Conclusions KAZN was involved in ovarian cancer pathogenesis. Our results demonstrate a new direction for ovarian cancer research and provide a potential diagnostic biomarker as well as a novel therapeutic target for clinical application.
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    Multiple genetic switches spontaneously modulating bacterial mutability
    (BioMed Central, 2010-09-13) Chen, Fang; Liu, Wei-Qiao; Eisenstark, Abraham; Johnston, Randal N.; Liu, Gui-Rong; Liu, Shu-Lin
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    Prediction of bacterial type IV secreted effectors by C-terminal features
    (BioMed Central, 2014-01-21) Wang, Yejun; Wei, Xiaowei; Bao, Hongxia; Liu, Shu-Lin
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    Production of enterodiol from defatted flaxseeds through biotransformation by human intestinal bacteria
    (BioMed Central, 2010-04-16) Wang, Cheng-Zhi; Ma, Xiao-Qing; Yang, Dong-Hui; Guo, Zhi-Rong; Liu, Gui-Rong; Zhao, Ge-Xin; Tang, Jie; Zhang, Ya-Nan; Ma, Miao; Ca, Shao-Qing; Ku, Bao-Shan; Liu, Shu-Lin
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    SPC-P1: a pathogenicity-associated prophage of Salmonella paratyphi C
    (BioMed Central, 2010-12-30) Zou, Qing-Hua; Li, Qing-Hai; Zhu, Hong-Yun; Feng, Ye; Li, Yong-Guo; Johnston, Randal N.; Liu, Gui-Rong; Liu, Shu-Lin