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Qi WY, Zheng SH, Li SZ, Wang W, Wang QY, Liu QY, Li XK, Zhang JX, Gan DN, Ye YA, Zao XB. Immune cells in metabolic associated fatty liver disease: Global trends and hotspots (2004-2024). World J Hepatol 2025; 17:103327. [DOI: 10.4254/wjh.v17.i3.103327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 02/07/2025] [Accepted: 03/05/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND The interplay between immune cells and metabolic associated fatty liver disease (MAFLD) is a critical research frontier, bridging immunology and hepatology. The bibliometric findings can guide future research and funding priorities in the field by highlighting key areas of focus and potential therapeutic targets.
AIM To analyze the literature on immune cells and MAFLD, identifying research trends and future hotspots.
METHODS A systematic search in the Web of Science Core Collection from January 1, 2004 to May 20, 2024, yielded 1936 articles on immune cells and MAFLD. Excluding non-research documents, the data were analyzed using R packages Cluster profiler, enrichplot, ggplot2, VOSviewer and CiteSpace. Visualizations were created for countries, institutions, authors, journals, fields, co-cited references, keywords, genes, and diseases, with gene a disease data from Citexs.
RESULTS The field gained momentum in 2006, with the United States of America and China as leading contributors. Key research themes included oxidative stress, metabolic syndrome, liver fibrosis, and the role of Kupffer cells. Bioinformatics identified interleukin-6, tumor necrosis factor and signal transducer and activator of transcription 3 as central proteins in immune responses and inflammation, suggesting potential therapeutic targets for MAFLD. Clinically, these hub genes play pivotal roles in the pathogenesis of MAFLD. For instance, targeting the tumor necrosis factor signaling pathway could reduce inflammation, while modulating interleukin-6 and signal transducer and activator of transcription 3 expression may improve metabolic function, offering new strategies for MAFLD therapy.
CONCLUSION This bibliometric analysis reports on the research hotspots and emerging trends in the field of immune cells and MAFLD, highlighting key proteins and potential therapeutic strategies through bioinformatics.
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Affiliation(s)
- Wen-Ying Qi
- Department of Spleen and Stomach Diseases, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
| | - Shi-Hao Zheng
- Department of Spleen and Stomach Diseases, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
| | - Si-Ze Li
- Department of Spleen and Stomach Diseases, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
| | - Wei Wang
- Department of Spleen and Stomach Diseases, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
| | - Qiu-Yue Wang
- Department of Spleen and Stomach Diseases, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
| | - Qi-Yao Liu
- Department of Spleen and Stomach Diseases, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
- Institute of Hepatology, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
| | - Xiao-Ke Li
- Department of Spleen and Stomach Diseases, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
- Institute of Hepatology, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
| | - Jia-Xin Zhang
- Department of Spleen and Stomach Diseases, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
- Institute of Hepatology, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
| | - Da-Nan Gan
- Department of Spleen and Stomach Diseases, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
- Institute of Hepatology, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
| | - Yong-An Ye
- Department of Spleen and Stomach Diseases, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
- Institute of Hepatology, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
| | - Xiao-Bin Zao
- Department of Spleen and Stomach Diseases, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
- Institute of Hepatology, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100700, China
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Li L, Yi Y, Shu X, Li J, Kang H, Chang Y. The Correlation Between Serum Copper and Non-alcoholic Fatty Liver Disease in American Adults: an Analysis Based on NHANES 2011 to 2016. Biol Trace Elem Res 2024; 202:4398-4409. [PMID: 38168830 DOI: 10.1007/s12011-023-04029-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 12/14/2023] [Indexed: 01/05/2024]
Abstract
Copper functions as an essential micronutrient influencing diverse metabolic processes in mammals, encompassing oxidative stress responses, lipid metabolism, and participation in enzymatic reactions. However, the impact of serum copper on non-alcoholic fatty liver disease (NAFLD) remains controversial. Our aim was to explore the precise correlation between serum copper and NAFLD in a large-scale population-based study. A total of 1377 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included in our study. The diagnosis of NAFLD and its progress to advanced liver fibrosis were based on serological indexes. One-way ANOVA, Kruskal-Wallis H test, and Chi-square test were used to access variations between quartiles groups of serum copper. We conducted multivariate-adjusted logistic regression models and subgroup analyses to investigate the association between serum copper and NAFLD, along with several metabolic diseases. Among the 1377 participants, 661 were diagnosed with NAFLD, and 141 of whom were classified into advanced liver fibrosis. Higher serum copper levels (≥ 21.00 μmol/L) were associated with an increased incidence of NAFLD (odds ratio (OR) = 2.07 (1.38-3.10), p < 0.001), as well as advanced liver fibrosis (OR = 2.40 (1.17-5.19), p = 0.025). Moreover, serum copper exhibited a positive correlation with hypertension, overweight, and abdominal obesity, all of which have been identified as risk factors of NAFLD. Additionally, female participants, under the age of 60, and with a higher body mass index (BMI) (> 24.9 kg/m2) emerged as the most vulnerable subgroup concerning the relationship between serum copper and NAFLD. In the U.S. population, a notable association has been identified, linking elevated serum copper to an increased susceptibility for both the onset and progression of NAFLD, along with several metabolic disorders associated with NAFLD. The adverse effects of excess copper warrant attention in the context of public health considerations.
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Affiliation(s)
- Lurao Li
- Department of Gastroenterology, Zhong Nan Hospital of Wuhan University, Wuhan, China
- Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China
| | - Yun Yi
- Department of Gastroenterology, Zhong Nan Hospital of Wuhan University, Wuhan, China
- Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China
| | - Xiawen Shu
- Department of Gastroenterology, Zhong Nan Hospital of Wuhan University, Wuhan, China
- Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China
| | - Jianghui Li
- Department of Gastroenterology, Zhong Nan Hospital of Wuhan University, Wuhan, China
- Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China
| | - Hui Kang
- Department of Gastroenterology, Zhong Nan Hospital of Wuhan University, Wuhan, China
- Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China
| | - Ying Chang
- Department of Gastroenterology, Zhong Nan Hospital of Wuhan University, Wuhan, China.
- Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China.
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Sun YD, Zhang H, Chen YQ, Wu CX, Chen ML, Xu HR, Wang S, Liu JZ, Han JJ. Overweight with HBV infection limited the efficacy of TACE in hepatocellular carcinoma by inhibiting the upregulated HMGB1. BMC Cancer 2021; 21:1063. [PMID: 34583662 PMCID: PMC8480082 DOI: 10.1186/s12885-021-08783-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 09/14/2021] [Indexed: 02/07/2023] Open
Abstract
Background Transarterial chemoembolization (TACE) is an effective treatment for patients with hepatocellular carcinoma (HCC). However, the impact of hepatitis B viral (HBV) infection and body mass index (BMI) on TACE is controversial. The present study aimed to compare the influence of HBV and high BMI on TACE outcomes in advanced HCC. Methods Based on HBV infection history and BMI, patients were assigned to different subgroups. Blood samples were collected and analyzed by an enzyme-linked immunosorbent assay (ELISA) kit. The primary endpoint was progression-free survival (PFS) and the overall survival (OS) in the population. Results Compared to overweight combined HBV patients who received TACE, people with normal weight or no viral infection had significantly better OS and PFS. Sex, age, portal vein tumor thrombus, BCLC, ECOG, and tumor diameter are the main risk factors affecting PFS and OS. Except for the postoperative fever, no significant difference was detected in adverse reactions. Irrespective of TACE, the average expression of HMGB1 in hepatitis or obesity patients was higher than that in normal individuals and did not show upregulation after TACE. Patients without overweight or HBV infection had a low expression of serum HMGB1 that was substantially upregulated after TACE. Conclusions In this study, overweight combined HBV infection patients had shorter PFS and OS than other HCC patients. Thus, HBV and BMI maybe two factors affecting the efficacy of TACE via upregulated HMGB1. 1. High BMI combined with HBV infection has a negative impact on the PFS and OS of HCC patients treated with TACE. 2. Irrespective of TACE, the average HMGB1 in hepatitis and obesity patients was higher than that in normal individuals, which was not upregulated after TACE. 3. Patients without overweight and HBV infection had a low level of serum concentration of HMGB1 before TACE that was upregulated after TACE. Compared to others, these patients have severe changes in HMGB1 in the peripheral blood after treatment, indicating a higher risk of acute liver injury. 4. Upregulated HMGB1 elevated the prognosis after TACE, but obesity and HBV infection resulted in the negative effect by inhibiting HMGB1 expression. 5. For advanced HCC, overweight combined HBV infection, PVTT, multiple lesions, and larger tumor diameter are negative factors for TACE.
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Affiliation(s)
- Yuan-Dong Sun
- Interventional Radiology Department, Shandong Cancer Hospital and Institute Affiliated Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Jinan, 250117, Shandong Province, China
| | - Hao Zhang
- Interventional Radiology Department, Shandong Cancer Hospital and Institute Affiliated Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Jinan, 250117, Shandong Province, China
| | - Ye-Qiang Chen
- Maternal and Child Health Care Hospital of Shandong Province, No 238, Jingshidong Raod, Jinan, 250014, Shandong Province, China
| | - Chun-Xue Wu
- Interventional Radiology Department, Shandong Cancer Hospital and Institute Affiliated Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Jinan, 250117, Shandong Province, China.,Shandong First Medical University, No. 6699, Qingdao Road, Jinan, 250062, Shandong Province, China
| | - Miao-Ling Chen
- Interventional Radiology Department, Shandong Cancer Hospital and Institute Affiliated Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Jinan, 250117, Shandong Province, China.,Shandong First Medical University, No. 6699, Qingdao Road, Jinan, 250062, Shandong Province, China
| | - Hui-Rong Xu
- Interventional Radiology Department, Shandong Cancer Hospital and Institute Affiliated Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Jinan, 250117, Shandong Province, China
| | - Shuo Wang
- Interventional Radiology Department, Shandong Cancer Hospital and Institute Affiliated Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Jinan, 250117, Shandong Province, China
| | - Jing-Zhou Liu
- Shandong First Medical University, No. 6699, Qingdao Road, Jinan, 250062, Shandong Province, China.
| | - Jian-Jun Han
- Interventional Radiology Department, Shandong Cancer Hospital and Institute Affiliated Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440, Jiyan Road, Jinan, 250117, Shandong Province, China. .,Shandong First Medical University, No. 6699, Qingdao Road, Jinan, 250062, Shandong Province, China.
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Feng X, Yu W, Li X, Zhou F, Zhang W, Shen Q, Li J, Zhang C, Shen P. Apigenin, a modulator of PPARγ, attenuates HFD-induced NAFLD by regulating hepatocyte lipid metabolism and oxidative stress via Nrf2 activation. Biochem Pharmacol 2017; 136:136-149. [PMID: 28414138 DOI: 10.1016/j.bcp.2017.04.014] [Citation(s) in RCA: 147] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 04/12/2017] [Indexed: 02/07/2023]
Abstract
Lipid metabolic disorders and oxidative stress in the liver are key steps in the progression of nonalcoholic fatty liver disease (NAFLD), which is a major risk factor for the development of metabolic syndrome. To date, no pharmacological treatment for this condition has been approved. Our previous study has found that the food-derived compound apigenin (Api) significantly attenuates obesity-induced metabolic syndrome by acting as a peroxisome proliferator-activated receptor gamma modulator (PPARM). Herein, a high fat diet (HFD) induced NAFLD model was used to dig out whether Api had the effect on NAFLD. The results showed that Api had obvious effect in restraining NAFLD progression, including attenuating HFD induced lipid accumulation and oxidative stress in vivo. As a PPARM, although Api did significantly inhibit the expression of PPARγ target genes encoding the protein associated with lipid metabolism, it had no obvious activating effect on PPARγ. Interestingly, we found that Api promoted Nrf2 into the nucleus, thereby markedly activating Nrf2 to inhibit the lipid metabolism related genes and increase the oxidative stress related genes. Further Nrf2 knockdown/knockout and overexpression experiments showed that Api regulating PPARγ target genes was dependent on Nrf2 activation and the activation of Nrf2 counteracted the activation effect of PPARγ by Api. Importantly, we also found that Api might bind with Nrf2 via auto dock and ITC assay. Therefore, our results indicate that Api ameliorates NAFLD by a novel regulating mode of Nrf2 and PPARγ in inhibiting lipid metabolism and oxidative stress abnormity.
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Affiliation(s)
- Xiujing Feng
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210023, China
| | - Wen Yu
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210023, China
| | - Xinda Li
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210023, China
| | - Feifei Zhou
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210023, China
| | - Wenlong Zhang
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210023, China
| | - Qi Shen
- Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China
| | - Jianxin Li
- Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China
| | - Can Zhang
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, China; Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
| | - Pingping Shen
- State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210023, China.
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