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"Hyo Jung Cho"

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"Hyo Jung Cho"

Original Article

GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma
Hyung Seok Kim, Jung Hwan Yoon, Ji Yi Choi, Moon Gyeong Yoon, Geum Ok Baek, Minji Kang, Se Ha Jang, Won Park, Yunjin Go, Jestlin Tianthing Ng, Suk Woo Nam, Jee-Yeong Jeong, Ji Eun Han, Hyo Jung Cho, Su Bin Lim, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
Clin Mol Hepatol 2025;31(3):914-934.
Published online February 6, 2025
DOI: https://doi.org/10.3350/cmh.2024.1038
Background/Aims
Hepatocellular carcinoma (HCC) is characterized by high recurrence and mortality, necessitating the identification of reliable biomarkers. In this study, we aimed to identify the predictive gene signatures for HCC recurrence and evaluate the efficiency of GULP PTB domain-containing engulfment adaptor 1 (GULP1) as a predictive and diagnostic marker and therapeutic target for HCC.
Methods
We analyzed genomic datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases via least absolute shrinkage and selection operator Cox regression and 10-fold cross-validation, leading to the development of a 15-gene risk score model, which was validated using three independent datasets. Serum GULP1 and α-fetoprotein levels were assessed to determine the diagnostic accuracy of the model. Using clinical cohorts and patient sera, GULP1 roles were examined, and functional assays in vitro and in vivo were used to evaluate its effects on cell growth, epithelial–mesenchymal transition (EMT), ADP-ribosylation factor 6 (ARF6) activation, and β-catenin signaling.
Results
Our newly developed risk-score model accurately predicted recurrent HCC in all datasets. Among the 15 genes in the risk score model, GULP1 was overexpressed in patients with HCC and independently predicted HCC recurrence. Its expression modulation influenced cell growth and EMT, with observed effects on ARF6 activation and β-catenin signaling pathways.
Conclusions
GULP1 is a crucial biomarker for HCC, serving as a non-invasive diagnostic and predictive tool. It also plays key roles in HCC progression. Our findings highlight the potential use of GULP1 in treatment strategies targeting EMT and HCC recurrence to improve the personalized care and patient outcomes.

Citations

Citations to this article as recorded by  Crossref logo
  • The evolving landscape of biomarkers for systemic therapy in advanced hepatocellular carcinoma
    Xinyu Guo, Zhongwei Zhao, Lingyi Zhu, Shuang Liu, Lingling Zhou, Fazong Wu, Shiji Fang, Minjiang Chen, Liyun Zheng, Jiansong Ji
    Biomarker Research.2025;[Epub]     CrossRef
  • Advances in research regarding epithelial-mesenchymal transition and prostate cancer
    Xi Wei, Rui Liu, Wei Li, Qi Yu, Qing Tao Yang, Tao Li
    Frontiers in Cell and Developmental Biology.2025;[Epub]     CrossRef
  • Correspondence: Response to the Letter Regarding "GULP1 as a Novel Diagnostic and Predictive Biomarker in Hepatocellular Carcinoma"
    Hyung Seok Kim, Soon Sun Kim, Jae Youn Cheong, Jung Woo Eun
    Clinical and Molecular Hepatology.2025;[Epub]     CrossRef
  • Serum Proteomic Profile Based on the TGF‐β Pathway Stratifies Risk of Hepatocellular Carcinoma
    Xiyan Xiang, Kirti Shetty, Herbert Yu, Bibhuti Mishra, Linda L. Wong, Xianghong Jasmine Zhou, Sanjaya K. Satapathy, James M. Crawford, Patricia S. Latham, Steven‐Huy Han, Brandon Mathew, Nabil N. Dagher, Lawrence Lau, Fellanza Cacaj, Anil K. Vegesna, Srin
    Liver International.2025;[Epub]     CrossRef
  • Systematic analysis of the expression profiles and prognostic values of the FAM72 family in liver cancer
    Weihao Kong, Long Teng, Kangjie Zhang, Yajun Zou, Xingyu Wang, Jianlin Zhang
    Biochemistry and Biophysics Reports.2025; 44: 102358.     CrossRef
  • 11,052 View
  • 974 Download
  • 4 Web of Science
  • Crossref

Correspondence

Hepatic neoplasm

Citations

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  • Matrisomics: Beyond the extracellular matrix for unveiling tumor microenvironment
    Jiwon Hong, Hyo Joon Jin, Mi Ran Choi, Darren Wan-Teck Lim, Jong-Eun Park, You-Sun Kim, Su Bin Lim
    Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2024; 1879(6): 189178.     CrossRef
  • 3,884 View
  • 81 Download
  • Crossref

Original Article

Hepatic neoplasm

Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma
Jiwon Hong, Jung Woo Eun, Geum Ok Baek, Jae Youn Cheong, Seryoung Park, Soon Sun Kim, Hyo Jung Cho, Su Bin Lim
Clin Mol Hepatol 2024;30(3):360-374.
Published online March 15, 2024
DOI: https://doi.org/10.3350/cmh.2024.0042
Background/Aims
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Despite identification of several biomarkers for HCC diagnosis, challenges such as low sensitivity and intratumoral heterogeneity have impeded early detection, highlighting the need for etiology-specific blood biomarkers.
Methods
We generated whole-transcriptome sequencing (WTS) and targeted proteome data from buffy coat and plasma samples from HCC patients. By integrating etiological information on viral infection, we investigated the etiology-specific gene expression landscape at the blood level. Validation of differentially expressed genes (DEGs) was performed using publicly available RNA-seq datasets and qRT‒PCR with AUC analyses.
Results
Differential expression analyses with multiomics data revealed distinct gene expression profiles between HBV-associated HCC and nonviral HCC, indicating the presence of etiology-specific blood biomarkers. The identified DEGs were validated across multiple independent datasets, underscoring their utility as biomarkers. Additionally, single-cell RNA-seq analysis of HCC confirmed differences in DEG expression across distinct immune cell types.
Conclusions
Our buffy coat WTS data and plasma proteome data may serve as reliable sources for identifying etiology-specific blood biomarkers of HCC and might contribute to discovery of therapeutic targets for HCC across different etiologies.

Citations

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  • Relevance of proteomics and metabolomics approaches to overview the tumorigenesis and better management of cancer
    Pooja Singh, Yashika W. Dhir, Shagun Gupta, Ankur Kaushal, Deepak Kala, Rupak Nagraiik, Naveen K. Kaushik, Md Salik Noorani, Abdul R. Asif, Bharat Singh, Shahbaz Aman, Sunny Dhir
    3 Biotech.2025;[Epub]     CrossRef
  • Development of a big data platform for collecting and utilizing clinical information from the Korea Biobank Network
    Yun Seon Im, Seol Whan Oh, Ki Hoon Kim, Wona Choi, In Young Choi
    BMC Medical Informatics and Decision Making.2025;[Epub]     CrossRef
  • Harnessing plasma transcriptomics for non-invasive cancer biomarker identification: a comprehensive review
    Nur Mazidah Haji Noor Mohamed, Nurulisa Zulkifle, Siti Razila Abdul Razak
    Discover Oncology.2025;[Epub]     CrossRef
  • Unveiling etiology-specific blood biomarkers in hepatocellular carcinoma: A gateway to personalized medicine: Editorial on “Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma”
    Joseph C. Ahn, Ju Dong Yang
    Clinical and Molecular Hepatology.2024; 30(4): 689.     CrossRef
  • Technology and Future of Multi-Cancer Early Detection
    Danny A. Milner, Jochen K. Lennerz
    Life.2024; 14(7): 833.     CrossRef
  • Correspondence to editorial on “Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma”
    Su Bin Lim, Hyo Jung Cho
    Clinical and Molecular Hepatology.2024; 30(4): 1009.     CrossRef
  • 9,015 View
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  • 4 Web of Science
  • Crossref

Editorial

Hepatic neoplasm

  • 5,062 View
  • 79 Download
Original Articles

Viral hepatitis

Serum transferrin as a liver fibrosis biomarker in patients with chronic hepatitis B
Hyo Jung Cho, Soon Sun Kim, Seun Joo Ahn, Joo Han Park, Dong Joon Kim, Young Bae Kim, Sung Won Cho, Jae Youn Cheong
Clin Mol Hepatol 2014;20(4):347-354.
Published online December 24, 2014
DOI: https://doi.org/10.3350/cmh.2014.20.4.347
Background/Aims

Transferrin and alpha-1 antitrypsin are reportedly associated with liver fibrosis. We evaluated the usefulness of serum transferrin and alpha-1 antitrypsin as new liver fibrosis markers in patients with chronic hepatitis B.

Methods

The study included 293 patients with chronic hepatitis B who underwent a liver biopsy between October 2005 and June 2009, and who had no history of hepatocellular carcinoma. Serum markers and liver fibrosis stages were compared.

Results

Univariate analysis revealed that age (P<0.001), serum platelet count (P<0.001), and serum alkaline phosphatase level (P=0.003) differed significantly between the patients with and without liver cirrhosis. Serum transferrin levels were significantly lower in advanced fibrosis than in mild fibrosis in both univariate analysis (P=0.002) and multivariate analysis (P=0.009). In addition, the serum transferrin level was significantly lower in cirrhotic patients than in noncirrhotic patients (P=0.020). However, the serum level of alpha-1 antitrypsin was not significantly associated with liver cirrhosis in patients with chronic hepatitis B.

Conclusions

Serum transferrin could be promising serum marker for predicting advanced liver fibrosis in patients with chronic hepatitis B.

Citations

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  • Ellagic acid alleviates iron overload-induced liver damage by mitigating ferroptosis through modulation of the TGFβ/Smad signaling pathway
    Hangjie Fu, Wenxia Li, Qimei Cheng, Zhiwei Weng, Zhiguang Huang, Lijian Zhu, Tao Ding, Bin Ding
    Food Research International.2025; 214: 116590.     CrossRef
  • Evaluation of Transferrin Level in Iron Supplementation after Partial Hepatectomy
    Weiwei Fang, Chang Pang, Xiying Li
    Bulletin of Experimental Biology and Medicine.2025; 179(3): 348.     CrossRef
  • Iron Metabolism Genes Shape the Course of Liver Fibrosis in Chronic Hepatitis C: From Disease Progression to Reversal After Direct-Acting Antivirals Treatment
    Joana Ferreira, Manuel Bicho, Paula Faustino, Fátima Serejo
    Viruses.2025; 17(10): 1302.     CrossRef
  • Novel index for the prediction of significant liver fibrosis and cirrhosis in chronic hepatitis B patients in China
    Min-Jun Liao, Jun Li, Wei Dang, Dong-Bo Chen, Wan-Ying Qin, Pu Chen, Bi-Geng Zhao, Li-Ying Ren, Ting-Feng Xu, Hong-Song Chen, Wei-Jia Liao
    World Journal of Gastroenterology.2022; 28(27): 3503.     CrossRef
  • Proteomic and molecular evidences of Il1rl2, Ric8a, Krt18 and Hsp90b1 modulation during experimental hepatic fibrosis and pomegranate supplementation
    Hadiya Husain, Mohammad Waseem, Riaz Ahmad
    International Journal of Biological Macromolecules.2021; 185: 696.     CrossRef
  • Identification and characterization of substrates crosslinked by transglutaminases in liver and kidney fibrosis
    Hideki Tatsukawa, Taishu Takeuchi, Yoshiki Shinoda, Kiyotaka Hitomi
    Analytical Biochemistry.2020; 604: 113629.     CrossRef
  • Serum Transferrin Is an Independent Predictor of Mortality in Severe Alcoholic Hepatitis: Upping the Game or Just Upping the Ante?
    Kedhara G. Sainath, Arun Vasan, Virendra Singh
    American Journal of Gastroenterology.2020; 115(7): 1136.     CrossRef
  • Hepatic transferrin plays a role in systemic iron homeostasis and liver ferroptosis
    Yingying Yu, Li Jiang, Hao Wang, Zhe Shen, Qi Cheng, Pan Zhang, Jiaming Wang, Qian Wu, Xuexian Fang, Lingyan Duan, Shufen Wang, Kai Wang, Peng An, Tuo Shao, Raymond T. Chung, Shusen Zheng, Junxia Min, Fudi Wang
    Blood.2020; 136(6): 726.     CrossRef
  • Progress of non-invasive diagnostic of liver fibrosis: review of modern laboratory methods
    E. A. Kulebina, A. N. Surkov
    Meditsinskiy sovet = Medical Council.2020; (11): 224.     CrossRef
  • Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model
    Fanshuang Zhang, Yanying Ni, Yuan Yuan, Wei Yin, Youhe Gao
    Science China Life Sciences.2018; 61(11): 1369.     CrossRef
  • Clinical significance of decoy receptor 3 upregulation in patients with hepatitis B and liver fibrosis
    Xiaoli Lou, Yanqiang Hou, Hui Cao, Jingjing Zhao, Fengting Zhu
    Oncology Letters.2018;[Epub]     CrossRef
  • Low transferrin and high ferritin concentrations are associated with worse outcome in acute liver failure
    Olympia E. Anastasiou, Julia Kälsch, Mahdi Hakmouni, Ozlem Kucukoglu, Dominik Heider, Johannes Korth, Paul Manka, Jan‐Peter Sowa, Lars Bechmann, Fuat H. Saner, Andreas Paul, Guido Gerken, Hideo A. Baba, Ali Canbay
    Liver International.2017; 37(7): 1032.     CrossRef
  • Automated microfluidic platform of bead-based electrochemical immunosensor integrated with bioreactor for continual monitoring of cell secreted biomarkers
    Reza Riahi, Seyed Ali Mousavi Shaegh, Masoumeh Ghaderi, Yu Shrike Zhang, Su Ryon Shin, Julio Aleman, Solange Massa, Duckjin Kim, Mehmet Remzi Dokmeci, Ali Khademhosseini
    Scientific Reports.2016;[Epub]     CrossRef
  • Identification of Candidate Serum Biomarkers for Schistosoma mansoni Infected Mice Using Multiple Proteomic Platforms
    Manal I. Kardoush, Brian J. Ward, Momar Ndao, Salah A Sheweita
    PLOS ONE.2016; 11(5): e0154465.     CrossRef
  • Proteomic profiling of HBV infected liver biopsies with different fibrotic stages
    Seyma Katrinli, Kamil Ozdil, Abdurrahman Sahin, Oguzhan Ozturk, Gozde Kir, Ahmet Tarik Baykal, Emel Akgun, Omer Sinan Sarac, Mehmet Sokmen, H. Levent Doğanay, Gizem Dinler Doğanay
    Proteome Science.2016;[Epub]     CrossRef
  • Risk factors for incisional hernia after hepatic resection for hepatocellular carcinoma in patients with liver cirrhosis
    Hiroto Kayashima, Takashi Maeda, Noboru Harada, Takanobu Masuda, Atsushi Guntani, Shuhei Ito, Ayumi Matsuyama, Motohiro Hamatake, Shinichi Tsutsui, Hiroyuki Matsuda, Teruyoshi Ishida
    Surgery.2015; 158(6): 1669.     CrossRef
  • Current strategies and findings in clinically relevant post-translational modification-specific proteomics
    Oliver Pagel, Stefan Loroch, Albert Sickmann, René P Zahedi
    Expert Review of Proteomics.2015; 12(3): 235.     CrossRef
  • Non-invasive diagnosis of liver fibrosis and cirrhosis
    Yoav Lurie
    World Journal of Gastroenterology.2015; 21(41): 11567.     CrossRef
  • 11,376 View
  • 132 Download
  • 19 Web of Science
  • Crossref

Viral hepatitis

Association between apolipoprotein E genotype, chronic liver disease, and hepatitis B virus
Seun Joo Ahn, Dong Kyu Kim, Soon Sun Kim, Chang Bum Bae, Hyo Jung Cho, Han Gyeol Kim, Young Jip Kim, Joo Ho Lee, Hyo Jin Lee, Mi Yeon Lee, Kee Bum Kim, Jin Hee Cho, Sung Won Cho, Jae Youn Cheong
Korean J Hepatol 2012;18(3):295-301.
Published online September 25, 2012
DOI: https://doi.org/10.3350/cmh.2012.18.3.295
Background/Aims

Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies.

Methods

This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits.

Results

The ε3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%, and 9.9% for the ε2, ε3, and ε4 alleles, respectively. Significantly more of those patients carrying the ε3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype.

Conclusions

The ApoE ε3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls.

Citations

Citations to this article as recorded by  Crossref logo
  • Lipid‐Lowering Drugs and Pulmonary Vascular Disease: A Mendelian Randomization Study
    Xingya Yuan, Peiwei Hong, JinQiu Zhou
    Pulmonary Circulation.2025;[Epub]     CrossRef
  • HDL-based therapeutics: A promising frontier in combating viral and bacterial infections
    Alankrita Rani, Julia T. Stadler, Gunther Marsche
    Pharmacology & Therapeutics.2024; 260: 108684.     CrossRef
  • The Culprit Behind HBV-Infected Hepatocytes: NTCP
    Shenghao Li, Liyuan Hao, Jiali Deng, Junli Zhang, Fei Yu, Fanghang Ye, Na Li, Xiaoyu Hu
    Drug Design, Development and Therapy.2024; Volume 18: 4839.     CrossRef
  • Hepatitis B Virus Targets Lipid Transport Pathways to Infect Hepatocytes
    Knud Esser, Xiaoming Cheng, Jochen M. Wettengel, Julie Lucifora, Lea Hansen-Palmus, Katharina Austen, Armando A. Roca Suarez, Sarah Heintz, Barbara Testoni, Firat Nebioglu, Minh Tu Pham, Shangqing Yang, Alma Zernecke, Dirk Wohlleber, Marc Ringelhan, Mathi
    Cellular and Molecular Gastroenterology and Hepatology.2023; 16(2): 201.     CrossRef
  • Apolipoprotein E and viral infection: Risks and Mechanisms
    Feng Chen, Qiongwei Ke, Wenyan Wei, Lili Cui, Yan Wang
    Molecular Therapy - Nucleic Acids.2023; 33: 529.     CrossRef
  • Apolipoprotein E, a Crucial Cellular Protein in the Lifecycle of Hepatitis Viruses
    Yannick Tréguier, Anne Bull-Maurer, Philippe Roingeard
    International Journal of Molecular Sciences.2022; 23(7): 3676.     CrossRef
  • Risk Factors for Severe COVID-19 and Hepatitis C Infections: The Dual Role of Apolipoprotein E4
    Felipe B. Lima, Karine C. Bezerra, José Carlos R. Nascimento, Gdayllon C. Meneses, Reinaldo B. Oriá
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • Apolipoprotein E polymorphism influences orthotopic liver transplantation outcomes in patients with hepatitis C virus-induced liver cirrhosis
    José Carlos Rodrigues Nascimento, Lianna C Pereira, Juliana Magalhães C Rêgo, Ronaldo P Dias, Paulo Goberlânio B Silva, Silvio Alencar C Sobrinho, Gustavo R Coelho, Ivelise Regina C Brasil, Edmilson F Oliveira-Filho, James S Owen, Pierluigi Toniutto, Rein
    World Journal of Gastroenterology.2021; 27(11): 1064.     CrossRef
  • Impact of apolipoprotein E genetic polymorphisms on liver disease: An essential review
    José C.R. Nascimento, Gabriella A. Matos, Lianna C. Pereira, Anderson E.C.C.B. Mourão, Aline M. Sampaio, Reinaldo B. Oriá, Pierluigi Toniutto
    Annals of Hepatology.2020; 19(1): 24.     CrossRef
  • APOE ϵ 4 modifies the relationship between infectious burden and poor cognition
    Chen Zhao, Kevin Strobino, Yeseon Park Moon, Ying Kuen Cheung, Ralph L. Sacco, Yaakov Stern, Mitchell S.V. Elkind
    Neurology Genetics.2020;[Epub]     CrossRef
  • ApoE deficiency promotes hepatic pathology by aggravating Th17/Treg imbalance in murine schistosomiasis japonica
    Fei Guan, Chongyang Zhang, Chunjie Jiang, Muziazia Lupemba Jacques, Yang Bai, Shengjun Lu, Wenqi Liu, Jiahui Lei
    Parasite Immunology.2020;[Epub]     CrossRef
  • Long-term effects of low-dose mouse liver irradiation involve ultrastructural and biochemical changes in hepatocytes that depend on lipid metabolism
    Malgorzata Lysek-Gladysinska, Anna Wieczorek, Anna Walaszczyk, Karol Jelonek, Artur Jozwik, Monika Pietrowska, Wolfgang Dörr, Dorota Gabrys, Piotr Widlak
    Radiation and Environmental Biophysics.2018; 57(2): 123.     CrossRef
  • Lipase inhibitor orlistat prevents hepatitis B virus infection by targeting an early step in the virus life cycle
    Knud Esser, Julie Lucifora, Jochen Wettengel, Katrin Singethan, Almut Glinzer, Alma Zernecke, Ulrike Protzer
    Antiviral Research.2018; 151: 4.     CrossRef
  • Causal relevance of circulating high-density lipoprotein cholesterol with cancer: a Mendelian randomization meta-analysis
    Chunhua Yang, Geng Tian, Jia Mi, Xiaodan Wei, Xuri Li, Xianglin Li, Wenming Wang, Bin Wang
    Scientific Reports.2015;[Epub]     CrossRef
  • Gene expression profiling of MYC-driven tumor signatures in porcine liver stem cells by transcriptome sequencing
    Rajagopal N Aravalli, Neil C Talbot, Clifford J Steer
    World Journal of Gastroenterology.2015; 21(7): 2011.     CrossRef
  • The role of von Willebrand factor as a biomarker of tumor development in hepatitis B virus-associated human hepatocellular carcinoma: A quantitative proteomic based study
    Yi Liu, Xiwei Wang, Sanglin Li, Huaidong Hu, Dazhi Zhang, Peng Hu, Yixuan Yang, Hong Ren
    Journal of Proteomics.2014; 106: 99.     CrossRef
  • Association between apolipoprotein E genotype and cancer susceptibility: a meta-analysis
    R. Anand, S. S. Prakash, R. Veeramanikandan, Richard Kirubakaran
    Journal of Cancer Research and Clinical Oncology.2014; 140(7): 1075.     CrossRef
  • Human Plasma Lipid Modulation in Schistosomiasis Mansoni Depends on Apolipoprotein E Polymorphism
    Caíque Silveira Martins da Fonseca, Adenor Almeida Pimenta Filho, Bianka Santana dos Santos, César Augusto da Silva, Ana Lúcia Coutinho Domingues, James Stuart Owen, Vera Lúcia de Menezes Lima, Monica Uddin
    PLoS ONE.2014; 9(7): e101964.     CrossRef
  • Differential Regulation of Host Genes Including Hepatic Fatty Acid Synthase in HBV-Transgenic Mice
    Hongmin Zhang, Hong Li, Yixuan Yang, Sanglin Li, Hong Ren, Dazhi Zhang, Huaidong Hu
    Journal of Proteome Research.2013; 12(6): 2967.     CrossRef
  • 11,141 View
  • 80 Download
  • Crossref