Browsing by Author "Zhang, Ting"

Now showing 1 - 7 of 7
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    Alcohol Metabolizing Enzymes, Microsomal Ethanol Oxidizing System, Cytochrome P450 2E1, Catalase, and Aldehyde Dehydrogenase in Alcohol-Associated Liver Disease
    (MDPI, 2020-03) Jiang, Yanchao; Zhang, Ting; Kusumanchi, Praveen; Han, Sen; Yang, Zhihong; Liangpunsakul, Suthat; Medicine, School of Medicine
    Once ingested, most of the alcohol is metabolized in the liver by alcohol dehydrogenase to acetaldehyde. Two additional pathways of acetaldehyde generation are by microsomal ethanol oxidizing system (cytochrome P450 2E1) and catalase. Acetaldehyde can form adducts which can interfere with cellular function, leading to alcohol-induced liver injury. The variants of alcohol metabolizing genes encode enzymes with varied kinetic properties and result in the different rate of alcohol elimination and acetaldehyde generation. Allelic variants of these genes with higher enzymatic activity are believed to be able to modify susceptibility to alcohol-induced liver injury; however, the human studies on the association of these variants and alcohol-associated liver disease are inconclusive. In addition to acetaldehyde, the shift in the redox state during alcohol elimination may also link to other pathways resulting in activation of downstream signaling leading to liver injury.
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    Critical Role of microRNA-21 in the Pathogenesis of Liver Diseases
    (Frontiers Media, 2020-01-31) Zhang, Ting; Yang, Zhihong; Kusumanchi, Praveen; Han, Sen; Liangpunsakul, Suthat; Medicine, School of Medicine
    MicroRNAs are small non-coding RNAs that range in length from 18 to 24 nucleotides. As one of the most extensively studied microRNAs, microRNA-21 (miR-21) is highly expressed in many mammalian cell types. It regulates multiple biological functions such as proliferation, differentiation, migration, and apoptosis. In this review, we summarized the mechanism of miR-21 in the pathogenesis of various liver diseases. While it is clear that miR-21 plays an important role in different types of liver diseases, its use as a diagnostic marker for specific liver disease or its therapeutic implication are not ready for prime time due to significant variability and heterogeneity in the expression of miR-21 in different types of liver diseases depending on the studies. Additional studies to further define miR-21 functions and its mechanism in association with each type of chronic liver diseases are needed before we can translate the bedside observations into clinical settings.
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    Domain Adaptation Tracker With Global and Local Searching
    (IEEE, 2018) Zhao, Fei; Zhang, Ting; Wu, Yi; Wang, Jinqiao; Tang, Ming; Medicine, School of Medicine
    For the convolutional neural network (CNN)-based trackers, most of them locate the target only within a local area, which makes the trackers hard to recapture the target after drifting into the background. Besides, most state-of-the-art trackers spend a large amount of time on training the CNN-based classification networks online to adapt to the current domain. In this paper, to address the two problems, we propose a robust domain adaptation tracker based on the CNNs. The proposed tracker contains three CNNs: a local location network (LL-Net), a global location network (GL-Net), and a domain adaptation classification network (DA-Net). For the former problem, if we come to the conclusion that the tracker drifts into the background based on the output of the LL-Net, we will search for the target in a global area of the current frame based on the GL-Net. For the latter problem, we propose a CNN-based DA-Net with a domain adaptation (DA) layer. By pre-training the DA-Net offline, the DA-Net can adapt to the current domain by only updating the parameters of the DA layer in one training iteration when the online training is triggered, which makes the tracker run five times faster than MDNet with comparable tracking performance. The experimental results show that our tracker performs favorably against the state-of-the-art trackers on three popular benchmarks.
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    Long non-coding RNAs in liver diseases: Focusing on nonalcoholic fatty liver disease, alcohol-related liver disease, and cholestatic liver disease
    (The Korean Association for the Study of the Liver, 2020-10) Han, Sen; Zhang, Ting; Kusumanchi, Praveen; Huda, Nazmul; Jiang, Yanchao; Yang, Zhihong; Liangpunsakul, Suthat; Medicine, School of Medicine
    Long non-coding RNAs (lncRNAs), a class of transcribed RNA molecules with the lengths exceeding 200 nucleotides, are not translated into protein. They can modulate protein-coding genes by controlling transcriptional and posttranscriptional processes. The dysregulation of lncRNAs has been related to various pathological disorders. In this review, we summarized the current knowledge of lncRNAs and their implications in the pathogenesis of three common liver diseases: nonalcoholic fatty liver disease, alcohol-related liver disease, and cholestatic liver disease. Future studies to further define the role of lncRNAs and their mechanisms in various types of liver diseases should be explored. An improved understanding from these studies will provide us a useful perspective leading to mechanism-based intervention by targeting specific lncRNAs for the treatment of liver diseases.
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    Stress-responsive gene FKBP5 mediates alcohol-induced liver injury through the hippo pathway and CXCL1 signaling
    (Wiley, 2021-09) Kusumanchi, Praveen; Liang, Tiebing; Zhang, Ting; Ross, Ruth Ann; Han, Sen; Chandler, Kristina; Oshodi, Adepeju; Jiang, Yanchao; Dent, Alexander L.; Skill, Nicholas J.; Huda, Nazmul; Ma, Jing; Yang, Zhihong; Liangpunsakul, Suthat; Medicine, School of Medicine
    Chronic alcohol drinking is a major risk factor for alcohol-associated liver disease (ALD). FK506-binding protein 51 (FKBP5), a co-chaperone protein, is involved in many key regulatory pathways. It is known to be involved in stress-related disorders but there are no reports regarding its role in ALD. This present study aimed to examine the molecular mechanism of FKBP5 in ALD. We found a significant increase in hepatic FKBP5 transcripts and protein expression in patients with ALD and mice fed with chronic-plus-single binge ethanol. Loss of Fkbp5 in mice protected against alcohol-induced hepatic steatosis and inflammation. Transcriptomic analysis revealed a significant reduction of Tead1 and Cxcl1 mRNA in ethanol-fed Fkbp5-/- mice. Ethanol-induced Fkbp5 expression was secondary to downregulation of methylation level at its 5′ UTR promoter region. The increase in Fkbp5 expression led to induction in transcription factor Tead1 through Hippo signaling pathway. Fkbp5 can interact with YAP upstream kinase, MST1, affecting its ability to phosphorylate YAP and the inhibitory effect of hepatic YAP phosphorylation by ethanol leading to YAP nuclear translocation and TEAD1 activation. Activation of TEAD1 led to increased expression of its novel target, CXCL1, a chemokine-mediated neutrophil recruitment, causing hepatic inflammation and neutrophil infiltration in our mouse model. Conclusion We identified a novel FKBP5-YAP-TEAD1-CXCL1 axis in the pathogenesis of ALD. Loss of FKBP5 ameliorates alcohol-induced liver injury through the Hippo pathway and CXCL1 signaling, suggesting its potential role as a target for the treatment of ALD.
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    Transcriptomic analysis reveals the miRNAs responsible for liver regeneration associated with mortality in alcoholic hepatitis
    (Wiley, 2021-11) Yang, Zhihong; Zhang, Ting; Kusumanchi, Praveen; Tang, Qing; Sun, Zhaoli; Radaeva, Svetlana; Peiffer, Brandon; Shah, Vijay H.; Kamath, Patrick; Gores, Greg J.; Sanyal, Arun; Chalasani, Naga; Jiang, Yanchao; Huda, Nazmul; Ma, Jing; Liangpunsakul, Suthat; Medicine, School of Medicine
    We conducted a comprehensive serum transcriptomic analysis to explore the roles of miRNAs in alcoholic hepatitis (AH) pathogenesis and their prognostic significance. Serum miRNA profiling was performed in 15 controls, 20 heavy drinkers without liver disease, and 65 patients with AH and compared to publicly available hepatic miRNA profiling in AH patients. Among the top 26 miRNAs, the expression of miR-30b-5p, miR-20a-5p, miR-146a-5p, and miR-26b-5p were significantly reduced in both serum and liver of AH patients. Pathway analysis of the potential targets of these miRNAs uncovered the genes related to DNA synthesis and cell cycle progression pathways, including RRM2, CCND1, CCND2, MYC, and PMAIP1. We found a significant increase in the protein expression of RRM2, CCND1, and CCND2, but not MYC and PMAIP1 in AH patients who underwent liver transplantation; miR-26b-5p and miR-30b-5p inhibited the 3’-UTR luciferase activity of RRM2 and CCND2, and miR-20a-5p reduced the 3’-UTR luciferase activity of CCND1 and CCND2. During a median follow-up of 346 days, 21% of AH patients died; these patients had higher BMI, MELD, serum miR-30b-5p, miR-20a-5p, miR-146a-5p, and miR-26b-5p than those who survived. Cox regression analysis showed BMI, MELD score, miR-20a-5p, miR-146a-5p, and miR-26b-5p predicted the mortality. Conclusion: Patients with AH attempt to deal with hepatocyte injury by down-regulating specific miRNAs and upregulating genes responsible for DNA synthesis and cell cycle progression. Higher expression of these miRNAs, suggestive of a diminished capacity in liver regeneration, predicts short-term mortality in AH patients.
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    Vibrio vulnificus induces mTOR activation and inflammatory responses in macrophages
    (PLOS, 2017-07-18) Xie, Dan-Li; Zheng, Meng-Meng; Zheng, Yi; Gao, Hui; Zhang, Jie; Zhang, Ting; Guo, Jian-Chun; Yang, X. Frank; Zhong, Xiao-Ping; Lou, Yong-Liang; Microbiology and Immunology, School of Medicine
    Vibrio vulnificus (V. vulnificus), a Gram-negative marine bacterium, can cause life-threatening primary septicemia, especially in patients with liver diseases. How V. vulnificus affects the liver and how it acts on macrophages are not well understood. In this report, we demonstrated that V. vulnificus infection causes a strong inflammatory response, marked expansion of liver-resident macrophages, and liver damage in mice. We demonstrated further that V. vulnificus activates mTOR in macrophages and inhibition of mTOR differentially regulates V. vulnificus induced inflammatory responses, suggesting the possibility of targeting mTOR as a strategy to modulate V. vulnificus induced inflammatory responses.