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127 results on '"Zhang, Li-Shu"'

6. Metagenomic study of the gut microbiota associated with cow milk consumption in Chinese peri-/postmenopausal women

Author

Tian, Bo, primary, Yao, Jia-Heng, additional, Lin, Xu, additional, Lv, Wan-Qiang, additional, Jiang, Lin-Dong, additional, Wang, Zhuo-Qi, additional, Shen, Jie, additional, Xiao, Hong-Mei, additional, Xu, Hanli, additional, Xu, Lu-Lu, additional, Cheng, Xiyu, additional, Shen, Hui, additional, Qiu, Chuan, additional, Luo, Zhe, additional, Zhao, Lan-Juan, additional, Yan, Qiong, additional, Deng, Hong-Wen, additional, and Zhang, Li-Shu, additional

Published
2022
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21. Installation of a cancer promoting WNT/SIX1 signaling axis by the oncofusion protein MLL-AF9

Author

Zhang, Li-shu, primary, Kang, Xunlei, additional, Lu, Jianming, additional, Zhang, Yuannyu, additional, Wu, Xiaofeng, additional, Wu, Guojin, additional, Zheng, Junke, additional, Tuladhar, Rubina, additional, Shi, Heping, additional, Wang, Qiaoling, additional, Morlock, Lorraine, additional, Yao, Huiyu, additional, Huang, Lily Jun-shen, additional, Maire, Pascal, additional, Kim, James, additional, Williams, Noelle, additional, Xu, Jian, additional, Chen, Chuo, additional, Zhang, Cheng Cheng, additional, and Lum, Lawrence, additional

Published
2019
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22. A new permutation strategy of pathway-based approach for genome-wide association study

Author

Chen Yuan, Li Jian, Guo Yan-Fang, Zhang Li-Shu, and Deng Hong-Wen

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Recently introduced pathway-based approach is promising and advantageous to improve the efficiency of analyzing genome-wide association scan (GWAS) data to identify disease variants by jointly considering variants of the genes that belong to the same biological pathway. However, the current available pathway-based approaches for analyzing GWAS have limited power and efficiency. Results We proposed a new and efficient permutation strategy based on SNP randomization for determining significance in pathway analysis of GWAS. The developed permutation strategy was evaluated and compared to two previously available methods, i.e. sample permutation and gene permutation, through simulation studies and a study on a real dataset. Results showed that the proposed permutation strategy is more powerful and efficient with greatly reducing the computational complexity. Conclusion Our findings indicate the improved performance of SNP permutation and thus render pathway-based analysis of GWAS more applicable and attractive.

Published
2009
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23. Gene Expression and RNA Splicing Imputation Identifies Novel Candidate Genes Associated with Osteoporosis.

Author

Yong Liu, Hui Shen, Greenbaum, Jonathan, Anqi Liu, Kuan-Jui Su, Li-Shu Zhang, Lei Zhang, Qing Tian, Hong-Gang Hu, Jin-Sheng He, Hong-Wen Deng, Liu, Yong, Shen, Hui, Liu, Anqi, Su, Kuan-Jui, Zhang, Li-Shu, Zhang, Lei, Tian, Qing, Hu, Hong-Gang, and He, Jin-Sheng

Subjects
BONE density, RNA splicing, GENE expression, ADIPOSE tissues, OVARIAN reserve, GENES, GENETIC regulation, OSTEOPOROSIS, RNA, GENE expression profiling, MOLECULAR structure, GENETIC techniques
Abstract

Context: Though genome-wide association studies (GWASs) have identified hundreds of genetic variants associated with osteoporosis related traits, such as bone mineral density (BMD) and fracture, it remains a challenge to interpret their biological functions and underlying biological mechanisms.Objective: Integrate diverse expression quantitative trait loci and splicing quantitative trait loci data with several powerful GWAS datasets to identify novel candidate genes associated with osteoporosis.Design, Setting, and Participants: Here, we conducted a transcriptome-wide association study (TWAS) for total body BMD (TB-BMD) (n = 66 628 for discovery and 7697 for validation) and fracture (53 184 fracture cases and 373 611 controls for discovery and 37 857 cases and 227 116 controls for validation), respectively. We also conducted multi-SNP-based summarized mendelian randomization analysis to further validate our findings.Results: In total, we detected 88 genes significantly associated with TB-BMD or fracture through expression or ribonucleic acid splicing. Summarized mendelian randomization analysis revealed that 78 of the significant genes may have potential causal effects on TB-BMD or fracture in at least 1 specific tissue. Among them, 64 genes have been reported in previous GWASs or TWASs for osteoporosis, such as ING3, CPED1, and WNT16, as well as 14 novel genes, such as DBF4B, GRN, TMUB2, and UNC93B1.Conclusions: Overall, our findings provide novel insights into the pathogenesis mechanisms of osteoporosis and highlight the power of a TWAS to identify and prioritize potential causal genes. [ABSTRACT FROM AUTHOR]

Published
2020
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25. Mechanosensing by Gli1+ cells contributes to the orthodontic force‐induced bone remodelling.

Author

Liu, An‐Qi, Zhang, Li‐Shu, Chen, Ji, Sui, Bing‐Dong, Liu, Jin, Zhai, Qi‐Ming, Li, Yan‐Jiao, Bai, Meng, Chen, Kai, Jin, Yan, Hu, Cheng‐Hu, and Jin, Fang

Subjects
*BONE remodeling, *CORRECTIVE orthodontics, *PERIODONTAL ligament, *BONE cells, *TRANSGENIC mice
Abstract

Objectives: Gli1+ cells have received extensive attention in tissue homeostasis and injury mobilization. The aim of this study was to investigate whether Gli1+ cells respond to force and contribute to bone remodelling. Materials and methods: We established orthodontic tooth movement (OTM) model to assess the bone response for mechanical force. The transgenic mice were utilized to label and inhibit Gli1+ cells, respectively. Additionally, mice that conditional ablate Yes‐associated protein (Yap) in Gli1+ cells were applied in the present study. The tooth movement and bone remodelling were analysed. Results: We first found Gli1+ cells expressed in periodontal ligament (PDL). They were proliferated and differentiated into osteoblastic cells under tensile force. Next, both pharmacological and genetic Gli1 inhibition models were utilized to confirm that inhibition of Gli1+ cells led to arrest of bone remodelling. Furthermore, immunofluorescence staining identified classical mechanotransduction factor Yap expressed in Gli1+ cells and decreased after suppression of Gli1+ cells. Additionally, conditional ablation of Yap gene in Gli1+ cells inhibited the bone remodelling as well, suggesting Gli1+ cells are force‐responsive cells. Conclusions: Our findings highlighted that Gli1+ cells in PDL directly respond to orthodontic force and further mediate bone remodelling, thus providing novel functional evidence in the mechanism of bone remodelling and first uncovering the mechanical responsive property of Gli1+ cells. [ABSTRACT FROM AUTHOR]

Published
2020
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27. Installation of a Cancer Promoting WNT/SIX1 Signaling Axis by the Oncofusion Protein MLL-AF9

Author

Zhang, Li-shu, primary, Kang, Xunlei, additional, Lu, Jianming, additional, Zhang, Yuannyu, additional, Wu, Xiaofeng, additional, Wu, Guojin, additional, Zheng, Junke, additional, Tuladhar, Rubina, additional, Shi, Heping, additional, Wang, Qiaoling, additional, Morlock, Lorraine, additional, Yao, Huiyu, additional, Huang, Lily Jun-shen, additional, Maire, Pascal, additional, Kim, James, additional, Williams, Noelle, additional, Xu, Jian, additional, Chen, Chuo, additional, Zhang, Cheng Cheng, additional, and Lum, Lawrence, additional

Published
2018
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28. Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor

Author

Wu, Xiaofeng, primary, Zhang, Li-shu, additional, Toombs, Jason, additional, Kuo, Yi-Chun, additional, Piazza, John Tyler, additional, Tuladhar, Rubina, additional, Barrett, Quinn, additional, Fan, Chih-wei, additional, Zhang, Xuewu, additional, Walensky, Loren D., additional, Kool, Marcel, additional, Cheng, Steven Y., additional, Brekken, Rolf, additional, Opferman, Joseph T., additional, Green, Douglas R., additional, Moldoveanu, Tudor, additional, and Lum, Lawrence, additional

Published
2017
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29. IL21R and PTH May Underlie Variation of Femoral Neck Bone Mineral Density as Revealed by a Genome-wide Association Study

Author

Guo, Yan, Zhang, Li-Shu, Yang, Tie-Lin, Tian, Qing, Xiong, Dong-Hai, Pei, Yu-Fang, and Deng, Hong-Wen

Subjects
Adult, Male, Femur Neck, Middle Aged, osteoporosis, Polymorphism, Single Nucleotide, IL21R, BMD, Bone Density, Parathyroid Hormone, genome-wide association, Humans, Original Article, Female, Receptors, Interleukin-21, PTH, Aged, Genome-Wide Association Study
Abstract

Bone mineral density (BMD) measured at the femoral neck (FN) is the most important risk phenotype for osteoporosis and has been used as a reference standard for describing osteoporosis. The specific genes influencing FN BMD remain largely unknown. To identify such genes, we first performed a genome-wide association (GWA) analysis for FN BMD in a discovery sample consisting of 983 unrelated white subjects. We then tested the top significant single-nucleotide polymorphisms (SNPs; 175 SNPs with p < 5 × 10−4) for replication in a family-based sample of 2557 white subjects. Combing results from these two samples, we found that two genes, parathyroid hormone (PTH) and interleukin 21 receptor (IL21R), achieved consistent association results in both the discovery and replication samples. The PTH gene SNPs, rs9630182, rs2036417, and rs7125774, achieved p values of 1.10 × 10−4, 3.24 × 10−4, and 3.06 × 10−4, respectively, in the discovery sample; p values of 6.50 × 10−4, 5.08 × 10−3, and 5.68 × 10−3, respectively, in the replication sample; and combined p values of 3.98 × 10−7, 9.52 × 10−6, and 1.05 × 10−5, respectively, in the total sample. The IL21R gene SNPs, rs8057551, rs8061992, and rs7199138, achieved p values of 1.51 × 10−4, 1.53 × 10−4, and 3.88 × 10−4, respectively, in the discovery sample; p values of 2.36 × 10−3, 6.74 × 10−3, and 6.41 × 10−3, respectively, in the replication sample; and combined p values of 2.31 × 10−6, 8.62 × 10−6, and 1.41 × 10−5, respectively, in the total sample. The effect size of each SNP was approximately 0.11 SD estimated in the discovery sample. PTH and IL21R both have potential biologic functions important to bone metabolism. Overall, our findings provide some new clues to the understanding of the genetic architecture of osteoporosis. © 2010 American Society for Bone and Mineral Research.

Published
2009

30. Corrigendum to “Quantitative proteomics and integrative network analysis identified novel genes and pathways related to osteoporosis” [J. Proteomics 142 (16 June 2016) 45–52]

Author

Zeng, Yong, primary, Zhang, Lan, additional, Zhu, Wei, additional, Xu, Chao, additional, He, Hao, additional, Zhou, Yu, additional, Liu, Yao-Zhong, additional, Tian, Qing, additional, Zhang, Ji-Gang, additional, Deng, Fei-Yan, additional, Hu, Hong-Gang, additional, Zhang, Li-Shu, additional, and Deng, Hong-Wen, additional

Published
2017
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32. Evaluation of Groundwater Budget and Assessment of Pumping Plans for Kang-Ping Development District Based on Modflow Simulations

Author

Yang Zhan-mei, Bian Jian-min, and Zhang Li-shu

Subjects
Hydrology, Ping (video games), Groundwater flow, Computer simulation, MODFLOW, Sustainability, Water resource management, Groundwater, Geology
Abstract

In order to prevent possible over-extraction of the groundwater and maintain sustainability of groundwater supply in Kang-Ping Developing District (KPDD), a numerical simulation model of groundwater flow system was built based on analyzing and conceptualizing the local geological and hydro-geological conditions and solved by Visual Modflow. The results show that the model-simulated water heads match the measured historical water heads well and the model can be used to predict the groundwater flow field evolution. Evolution of groundwater flow field in the next 15 years was predicted under different pumping condition.

Published
2011

33. Suggestion of GLYAT gene underlying variation of bone size and body lean mass as revealed by a bivariate genome-wide association study

Author

Guo, Yan-Fang, primary, Zhang, Li-Shu, additional, Liu, Yong-Jun, additional, Hu, Hong-Gang, additional, Li, Jian, additional, Tian, Qing, additional, Yu, Ping, additional, Zhang, Feng, additional, Yang, Tie-Lin, additional, Guo, Yan, additional, Peng, Xiang-Lei, additional, Dai, Meng, additional, Chen, Wei, additional, and Deng, Hong-Wen, additional

Published
2012
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34. Diverse Chemical Scaffolds Support Direct Inhibition of the Membrane-bound O-Acyltransferase Porcupine

Author

Dodge, Michael E., primary, Moon, Jesung, additional, Tuladhar, Rubina, additional, Lu, Jianming, additional, Jacob, Leni S., additional, Zhang, Li-shu, additional, Shi, Heping, additional, Wang, Xiaolei, additional, Moro, Enrico, additional, Mongera, Alessandro, additional, Argenton, Francesco, additional, Karner, Courtney M., additional, Carroll, Thomas J., additional, Chen, Chuo, additional, Amatruda, James F., additional, and Lum, Lawrence, additional

Published
2012
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35. Peripheral Blood Monocyte-expressed ANXA2 Gene is Involved in Pathogenesis of Osteoporosis in Humans

Author

Deng, Fei-Yan, primary, Lei, Shu-Feng, additional, Zhang, Yan, additional, Zhang, Yu-Ling, additional, Zheng, Yan-Peng, additional, Zhang, Li-Shu, additional, Pan, Rong, additional, Wang, Lili, additional, Tian, Qing, additional, Shen, Hui, additional, Zhao, Ming, additional, Lundberg, Yunxia Wang, additional, Liu, Yao-Zhong, additional, Papasian, Christopher J., additional, and Deng, Hong-Wen, additional

Published
2011
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39. Genome-Wide Association Study Identifies ALDH7A1 as a Novel Susceptibility Gene for Osteoporosis

Author

Guo, Yan, primary, Tan, Li-Jun, additional, Lei, Shu-Feng, additional, Yang, Tie-Lin, additional, Chen, Xiang-Ding, additional, Zhang, Feng, additional, Chen, Yuan, additional, Pan, Feng, additional, Yan, Han, additional, Liu, Xiaogang, additional, Tian, Qing, additional, Zhang, Zhi-Xin, additional, Zhou, Qi, additional, Qiu, Chuan, additional, Dong, Shan-Shan, additional, Xu, Xiang-Hong, additional, Guo, Yan-Fang, additional, Zhu, Xue-Zhen, additional, Liu, Shan-Lin, additional, Wang, Xiang-Li, additional, Li, Xi, additional, Luo, Yi, additional, Zhang, Li-Shu, additional, Li, Meng, additional, Wang, Jin-Tang, additional, Wen, Ting, additional, Drees, Betty, additional, Hamilton, James, additional, Papasian, Christopher J., additional, Recker, Robert R., additional, Song, Xiao-Ping, additional, Cheng, Jing, additional, and Deng, Hong-Wen, additional

Published
2010
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45. Identification of the serum metabolites associated with cow milk consumption in Chinese Peri-/Postmenopausal women.

Author

Tian, Bo, Xu, Lu-Lu, Jiang, Lin-Dong, Lin, Xu, Shen, Jie, Shen, Hui, Su, Kuan-Jui, Gong, Rui, Qiu, Chuan, Luo, Zhe, Yao, Jia-Heng, Wang, Zhuo-Qi, Xiao, Hong-Mei, Zhang, Li-Shu, and Deng, Hong-Wen

Subjects
*MILK consumption, *PARTIAL least squares regression, *BACTEROIDES fragilis, *CLIMACTERIC, *METABOLITES, *COWS, *DISCRIMINANT analysis
Abstract

AbstractCow milk consumption (CMC) and downstream alterations of serum metabolites are commonly considered important factors regulating human health status. Foods may lead to metabolic changes directly or indirectly through remodelling gut microbiota (GM). We sought to identify the metabolic alterations in Chinese Peri-/Postmenopausal women with habitual CMC and explore if the GM mediates the CMC-metabolite associations. 346 Chinese Peri-/Postmenopausal women participants were recruited in this study. Fixed effects regression and partial least squares discriminant analysis (PLS-DA) were applied to reveal alterations of serum metabolic features in different CMC groups. Spearman correlation coefficient was computed to detect metabolome-metagenome association. 36 CMC-associated metabolites including palmitic acid (FA(16:0)), 7alpha-hydroxy-4-cholesterin-3-one (7alphaC4), citrulline were identified by both fixed effects regression (FDR < 0.05) and PLS-DA (VIP score > 2). Some significant metabolite-GM associations were observed, including FA(16:0) with gut species Bacteroides ovatus, Bacteroides sp.D2. These findings would further prompt our understanding of the effect of cow milk on human health. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Peripheral Blood Monocyte-expressed ANXA2Gene is Involved in Pathogenesis of Osteoporosis in Humans*

Author

Deng, Fei-Yan, Lei, Shu-Feng, Zhang, Yan, Zhang, Yu-Ling, Zheng, Yan-Peng, Zhang, Li-Shu, Pan, Rong, Wang, Lili, Tian, Qing, Shen, Hui, Zhao, Ming, Lundberg, Yunxia Wang, Liu, Yao-Zhong, Papasian, Christopher J., and Deng, Hong-Wen

Abstract

Low bone mineral density (BMD) is a risk factor of osteoporosis and has strong genetic determination. Genes influencing BMD and fundamental mechanisms leading to osteoporosis have yet to be fully determined. Peripheral blood monocytes (PBM) are potential osteoclast precursors, which could access to bone resorption surfaces and differentiate into osteoclasts to resorb bone. Herein, we attempted to identify osteoporosis susceptibility gene(s) and characterize their function(s), through an initial proteomics discovery study on PBM in vivo, and multiscale validation studies in vivoand in vitro. Utilizing the quantitative proteomics methodology LC-nano-ESI-MSE, we discovered that a novel protein, i.e.ANXA2, was up-regulated twofold in PBM in vivoin Caucasians with extremely low BMD (cases) versusthose with extremely high BMD (controls) (n= 28, p< 0.05). ANXA2gene up-regulation in low BMD subjects was replicated at the mRNA level in PBM in vivoin a second and independent case-control sample (n= 80, p< 0.05). At the DNA level, we found that SNPs in the ANXA2gene were associated with BMD variation in a 3rdand independent case-control sample (n= 44, p< 0.05), as well as in a random population sample (n= 997, p< 0.05). The above integrative evidence strongly supports the concept that ANXA2is involved in the pathogenesis of osteoporosis in humans. Through a follow-up cellular functional study, we found that ANXA2 protein significantly promoted monocyte migration across an endothelial barrier in vitro(p< 0.001). Thus, elevated ANXA2 protein expression level, as detected in low BMD subjects, probably stimulates more PBM migration through the blood vessel walls to bone resorption surfaces in vivo, where they differentiate into higher number of osteoclasts and resorb bone at higher rates, thereby decreasing BMD. In conclusion, this study identified a novel osteoporosis susceptibility gene ANXA2, and suggested a novel pathophysiological mechanism, mediated by ANXA2, for osteoporosis in humans.

Published
2011
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47. Chemical Modulation of WNT Signaling in Cancer.

Author

Zhang LS and Lum L

Subjects
Humans, Neoplasms metabolism, Neoplasms pathology, Acyltransferases antagonists & inhibitors, Membrane Proteins antagonists & inhibitors, Neoplasms drug therapy, Pyrazines pharmacology, Pyridines pharmacology, Wnt Proteins metabolism, Wnt Signaling Pathway drug effects
Abstract

Genetically based observations stemming from defects in development and in regeneration form the foundation of our understanding regarding how the secreted WNT proteins control coordinated cell fate decision-making in adult tissues. At the same time, our anticipation of potential benefits and unwanted toxicities associated with candidate anticancer agents targeting WNT signal transduction are also reliant upon this blueprint of WNT-associated physiology. Despite the long established role of WNT signaling in cancer, the emergence of WNT signaling as a suppressor of immunological attack in melanoma reveals an unanticipated anticancer potential in targeting WNT signaling. Here we review the literature associated with WNT signaling in cancer and discuss potential challenges that may be associated with the chemical attack of this important cellular process in achieving therapeutic goals. Although a number of small molecules targeting WNT signaling are introduced here, we center our discussion on antagonists of the WNT acyltransferase porcupine (PORCN) given the recent entry of two candidate molecules in clinical testing., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Published
2018
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49. Delivery of the Porcupine Inhibitor WNT974 in Mice.

Author

Zhang LS and Lum L

Subjects
Acyltransferases genetics, Animals, Membrane Proteins genetics, Mice, Pyrazines administration & dosage, Pyridines administration & dosage, Wnt Proteins antagonists & inhibitors, Acyltransferases antagonists & inhibitors, Membrane Proteins antagonists & inhibitors, Molecular Biology methods, Wnt Proteins genetics, Wnt Signaling Pathway drug effects
Abstract

We describe here a technique for delivering the porcupine inhibitor WNT974 (formerly LGK974) in mice. The protocol entails once-a-day oral delivery of WNT974 for up to 3 months at a concentration sufficient to achieve systemic Wnt pathway inhibition with limited toxicity as measured by weight change. This route of delivery enables extended durations of Wnt signaling inhibition in a mammalian model organism.

Published
2016
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