Basic Hepatology最新文献

{"title":"IDDF2021-ABS-0202 Crotonylation of SEPT2 protein predicts poor prognosis in hepatocellular carcinoma","authors":"Xinyue Zhang, Ning Zhang, Lixia Xu, Xiaoxing Li","doi":"10.1136/gutjnl-2021-iddf.10","DOIUrl":"https://doi.org/10.1136/gutjnl-2021-iddf.10","url":null,"abstract":"IDDF2021-ABS-0205 Figure 1 Abstracts A8 Gut 2021;70(Suppl 2):A1–A150 on D ecem er 2, 2021 by gest. P rocted by coright. http/gut.bm jcom / G t: frst pulished as 10.113utjnl-2021-ID D F 11 on 2 S etem er 221. D ow nladed fom FBG (*P<0.05, **P<0.01, ***P< 0.001)) (IDDF2021-ABS0205 Figure 1f. Akkermansia viable improved liver steatosis; serum levels of HOMA-IR (**P<0.01, ***P< 0.001)). The a diversity of intestinal microflora in HFD group was lower than that in CD group. Compared with HFD group, The a diversity of intestinal microflora in HFD+LAKK group and HFD+ Supernatant group were increased (IDDF2021-ABS0205 Figure 1g. Akkermansia viable improved liver steatosis; Alpha diversity). PCoA analysis showed that there were differences among groups (IDDF2021-ABS-0205 Figure 1h. Akkermansia viable improved liver steatosis; PCoA analyses). Compared with CD group, the F/B ratio increased was increased in HFD group but decreased in HFD+LAKK group and the HFD+ Supernatant group (IDDF2021-ABS-0205 Figure 1i. Akkermansia viable improved liver steatosis; Phylum level of gut microbiota composition). The bacteria abundance of HFD group and HFD+ PAKK group was similar. HFD +LAKK group and HFD+ Supernatant group had similar bacteria abundances, such as the increasing of Akkermansia, Alloprevotella, and Roseburia (IDDF2021-ABS-0205 Figure 1j. Akkermansia viable improved liver steatosis; Bacterial heatmap at genus level. CD, control diet; HFD, high-fat diet; LAKK, Akkermansia viable; PAKK, pasteurized Akkermansia). Conclusions Akkermansia viable, pasteurized Akkermansia and supernatant improve glucose metabolism and insulin resistance, whereas Akkermansia viable and supernatant improve gut microbiota. Only Akkermansia viable can improve liver steatosis and lipid metabolism. Akkermansia viable effectively increases probiotics. Chuangyu Cao and Diwen Shou contributed equally to this work. Clinical Gastroenterology IDDF2021-ABS-0033 PROTECTIVE EFFECTS OF FEMALE REPRODUCTIVE FACTORS ON GASTRIC SIGNET RING CELL CARCINOMA Yang Li*. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China 10.1136/gutjnl-2021-IDDF.12 Background The overall incidence of gastric cancer is higher in males than in females worldwide. However, gastric signet ring cell carcinoma (GSRC) is more frequently observed in younger female patients. Limited studies focused on sex-specific differences in GSRC have been reported. Gastric cancer shows a male predominance that might be explained by protective effects from estrogens in females. The aim of this study was to analyze clinicopathological differences between sex groups to reveal sex disparities in GSRC. Methods We reviewed medical records for and surveying reproductive factors, to 1,431 patients who get treatment for GSRC at Cancer Hospital, Chinese Academy of Medical Sciences from January 2011 to December 2018. Clinicopathological characteristics","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117002603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IDDF2021-ABS-0115 Enhancer dysregulation of myeloid-derived suppressor cells in hepatocellular carcinoma","authors":"W. Law, Sze Lok Alfred Cheng, Jingying Zhou, Zhewen Xiong, Jianquan Cao","doi":"10.1136/gutjnl-2021-iddf.17","DOIUrl":"https://doi.org/10.1136/gutjnl-2021-iddf.17","url":null,"abstract":"Background Though immune checkpoint blockade (ICB) therapies have shown promise to treat HCC, the insufficient T cell infiltration to the non-inflamed tumor restricts the effectiveness of ICB therapy to a minority of HCC patients. As a key player in the tumor microenvironment (TME), myeloid-derived suppressor cells (MDSC) were reported to correlate with resistance to ICB and poor prognosis. Given the fact that enhancer reprogramming of MDSC is crucial to the MDSC identity and function, this study aims to identify the enhancer targets that are significantly contributing to MDSC immunosuppressiveness and to study the potential of myeloid targeting for improving immunotherapy efficacy. Methods Single-cell RNA sequencing (sc-RNA-seq) of ICB-resistant patients was performed to understand the immune profile of patients and the heterogeneity of TME in HCC. The expression and immune profile of MDSC signature genes were determined by flow cytometry analysis in immune cells from tumor-bearing mice and HCC patients. FANTOM5 (Functional Annotation of the Mammalian Genome) database and JEME (Joint Effects of Multiple Enhancers) algorithm were used to identify enhancer RNA (eRNA) locations and expressions. Functional significance and molecular mechanisms of signature genes were conducted by gene knockdown in human blood-derived MDSCs, followed by mRNA and protein detection, q-ChIP-PCR and multi-colour flow cytometry. Results MDSCs were negatively correlated with CD8+ T cell proportion in ICB-resistant patients. A novel MDSC signature gene, EREG has been identified. Its expression is correlated with non-responsiveness in HCC patients. It is enriched in MDSCs of HCC patients and correlated with poor prognosis. Moreover, high EREG expression is correlated with increased tumor size and decreased tumor-infiltrating lymphocytes in ICB resistance mouse models. Mechanistically, it was found that eRNAs control the upregulation of EREG in MDSCs. Inhibition of eRNAs could reduce MDSC proliferation and T cell suppressive activity. Conclusions Our data demonstrated the intricate interaction of enhancer regulation of EREG in MDSC and ICB resistance, delineating a new epigenetic mechanism underlying tumor immune evasion. Identifying this novel enhancer-regulated target might uncover new immunosuppressive mechanism and MDSC-directed strategy for improving HCC immunotherapy efficacy.","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132750776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IDDF2021-ABS-0138 Circulating non-coding transcripts serving as biomarkers for diabetic liver steatosis","authors":"Zhangting Wang, K. Miu, Sin-Hang Fung, C. Yu, W. Law, Heung Man Lee, A. Kong, Juliana C. N. Chan, Wai-Yee Chan","doi":"10.1136/gutjnl-2021-iddf.18","DOIUrl":"https://doi.org/10.1136/gutjnl-2021-iddf.18","url":null,"abstract":"","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130205378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IDDF2021-ABS-0207 Type 2 resistant starch improves liver steatosis induced by high-fat diet relating to gut microbiota regulation and concentration of propionic acid in portal vein blood in C57BL/6J mice","authors":"Diwen Shou, C. Cao, Haoming Xu, Hongli Huang, Yu Xia, Qing Mei, Y. Quan, Hanqing Chen, Chong Zhao, Wenjuan Tang, Huiting Chen, Yongjian Zhou","doi":"10.1136/gutjnl-2021-iddf.20","DOIUrl":"https://doi.org/10.1136/gutjnl-2021-iddf.20","url":null,"abstract":"","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"121 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116398434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IDDF2021-ABS-0205 Akkermansia viable bacteria improves liver steatosis induced by high-fat diet relating to the regulation of gut microbiota in C57BL/6J MICE","authors":"C. Cao, Diwen Shou, Haoming Xu, Hongli Huang, Yu Xia, Qing Mei, Y. Quan, Hanqing Chen, Chong Zhao, Wenjuan Tang, Huiting Chen, Yongjian Zhou","doi":"10.1136/gutjnl-2021-iddf.11","DOIUrl":"https://doi.org/10.1136/gutjnl-2021-iddf.11","url":null,"abstract":"","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127569387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IDDF2021-ABS-0204 SARS-COV-2 productively infects human liver and biliary organoids","authors":"Yi Zhao, Xiaoxue Ren, Xiaoxing Li, Lixia Xu, Jing Lu, Jun Yu","doi":"10.1136/gutjnl-2021-IDDF.19","DOIUrl":"https://doi.org/10.1136/gutjnl-2021-IDDF.19","url":null,"abstract":"Background SARS-CoV-2 has caused the COVID-19 pandemic, 14-53% with COVID-19 developed hepatic dysfunction. More data is required to ascertain the pattern of liver injury in patients with COVID-19. Here we report the use of human liver and biliary organoids as a tool to investigate the SARSCoV- 2 infection and virus-induced tissue damage ex vivo at the cellular and molecular levels. Methods Immunofluorescence staining and RT-qPCR was performed to examine the susceptibility and replication of human liver and biliary organoids to SARS-CoV-2. Transmission electron microscopy was performed to investigate the ultrastructure of SARS-CoV-2 infected biliary organoid. The mRNA sequence analysis was performed to determine gene expression changes induced by SARS-CoV-2-infection of biliary organoids. Results Immunofluorescence staining showed that SARS-CoV-2 spike (S) glycoprotein protein was readily detected in patchy areas of the human liver and biliary organoids, whereas no signal was found in uninfected control. RT-qPCR showed that the SARS-CoV-2 genomic RNAs revealed a dramatic increase of viral load in organoids at 24 h post-infection (MOI=1) and it can remain stable 96 hours in the liver organoids and 48 hours in biliary organoids. Unsupervised transmission electron microscopy (TEM) showed that viral particles occurred in the lumen of the organoid, at the basolateral and apical side of the organoid, even in membrane-bound vesicles. Additionally, RNA-seq revealed early cell response to virus infection, including the well-known upregulation of chemokines and inflammatory cytokines. Conclusions Therefore, the hepatocytes and bile duct cells have effectively been infected by COVID-19, and human liver and biliary organoids can serve as a pathophysiological model to investigate the underlying mechanism of SARS-CoV-2 infection.","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133212572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IDDF2019-ABS-0230 Change in the lipid profile, lipogenic and related enzymes in the livers of experimental diabetic rats: effect of trigonella foenum graecum and vanadate","authors":"Pardeep Kumar, N. Baquer","doi":"10.1136/GUTJNL-2019-IDDFABSTRACTS.102","DOIUrl":"https://doi.org/10.1136/GUTJNL-2019-IDDFABSTRACTS.102","url":null,"abstract":"Background Diabetes has been considered as one of the fastest growing epidemic worldwide; the number of people with diabetes is estimated to increase from 381.8 million in 2013 to 591.9 million in 2030. Oxidative stress in diabetic tissues is accompanied by a high level of free radicals and the simultaneously declined antioxidant enzymes status leading to cell membrane damage. In the present study, the effect of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP) administration has been studied on hepatic glucose homeostasis, lipogenic enzymes and lipid metabolism in liver tissues of the alloxan-induced diabetic rats and to see whether the treatment with SOV and TSP is capable of reversing these effects. Methods Diabetes was induced by administration of alloxan monohydrate (15 mg/100gm b.wt.) and rats were treated with 2IU insulin, 0.6 mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV with 5% TSP separately for 21 days. Control animals were given only the vehicle. The activities of two lipogenic enzymes, glucose-6-phosphate dehydrogenase and malic enzyme; and related enzymes, hexokinase and glucose-6-phosphatase were measured in the liver cytosolic fractions of diabetic rats and diabetic rats treated separately with TSP and SOV. The total lipids, triglycerides and cholesterol levels were estimated in the livers of the diabetic and the treated rats. Results Diabetic rats showed hyperglycemia with almost four-fold high blood glucose levels. The activities of both the lipogenic enzymes and hexokinase isozymes were significantly decreased whereas the activity of glucose-6-phosphatase was significantly increased in the diabetic liver. During diabetes, the levels of total lipids and triglycerides increased significantly with a decrease in the cholesterol levels in the liver. TSP and SOV were able to restore the altered enzyme activities to almost control levels. Rats treated with the combined dose of SOV and TSP had glucose levels comparable to controls, similar results were obtained with the triglycerides and cholesterol levels in the liver of diabetic rats. Conclusions Our results showed that lower doses of SOV (0.2 mg/ml) could be used in combination with TSP to effectively counter diabetic alterations without any toxic side effects.","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130047280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IDDF2019-ABS-0026 Metadoxine prevents diet-induced non-alcoholic steatohepatitis in mice","authors":"Du Jinghua, Lu Yu, Liu Dongdong, Nan Yue-min","doi":"10.1136/GUTJNL-2019-IDDFABSTRACTS.84","DOIUrl":"https://doi.org/10.1136/GUTJNL-2019-IDDFABSTRACTS.84","url":null,"abstract":"Background Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide. Metadoxine appears to be an effective strategy to manage alcoholic steatohepatitis. However, its role during non-alcoholic steatohepatitis (NASH) remains poorly defined. The study aimed to assess the therapeutic efficacy and mechanisms of metadoxine in NASH. Methods Male C57BL/6J mice were randomly divided into three groups of six animals. The treatments were as follows: 1): Control group: standard diet. 2) NASH group: 42% fat ‘high fat’ diet (HFD) ad libitum for 16 weeks. 3) Metadoxine group: HFD and a single oral dose of metadoxine (200 mg/kg). Mice body weight, liver weight, fat mass was measured. Sera were collected for the analysis of biochemical markers and livers were obtained for further histological staining and gene expression analysis. Transmission electron microscope (TEM) was used to observe the cell ultrastructure. The expression of inflammation genes, lipogenesis genes, and oxidative stress genes were assessed by real-time PCR and western blot. Results After the dietary intervention, metadoxine decreased body weight and liver weight compared to the HFD group. Liver sections showed that HFD mice developed marked macro- and microvesicular steatosis, as well as multifocal necrosis compared to the controls. However, metadoxine treatment abolished steatosis. Less lipid droplets were observed in the metadoxine treated animals in Oil Red O-stained sections. Metadoxine group showed lower serum concentrations of ALT, AST and TC, LDL-C than HFD mice. Moreover, we found mRNA levels of TNF-α, IL-1β, NF-κB were higher in HFD-fed mice than the control group. However, metadoxine treatment could decrease these genes and protein expression. In addition, metadoxine significantly increase the expression of lipogenesis genes (PPAR-α/γ, SREBP1c, FASN and ACO). Hepatic mRNA levels of oxidative stress genes were increased in HFD group, and metadoxine treatment further enhanced the expression of oxidative stress factors, such as NRF2, SOD1, NQO1. (figure 1,2,3) Conclusions Our data established a therapeutic role of metadoxine in NASH. Metadoxine has a protective effect on NASH and its mechanism may be related to decrease the lipid accumulation, inhibit the oxidative stress and ultimately deduce inflammation.","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131155616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IDDF2019-ABS-0221 Metabolic-immunoregulatory role of mTOR signaling in NAFLD-associated hepatocellular carcinoma","authors":"Wenshu Tang, Jingying Zhou, Weiqin Yang, Yu Feng, A. S. Cheng, M. T. Mok","doi":"10.1136/gutjnl-2019-iddfabstracts.100","DOIUrl":"https://doi.org/10.1136/gutjnl-2019-iddfabstracts.100","url":null,"abstract":"Background and objective Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and the second leading cause of cancer deaths worldwide. Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of disorders from simple steatosis to non-alcoholic steatohepatitis (NASH). Driven by the epidemics of obesity and diabetes, it is anticipated that NAFLD will become the most important cause of HCC. Activation of mammalian target of rapamycin (mTOR) pathway in NAFLD has been shown to promote deregulated lipid/glucose metabolism, immunosuppression and tumorigenesis. Methods To fully decipher the anti-immune surveillance functions of mTOR pathway in NAFLD-associated HCC, we performed immune cell profiling and signaling characterization in a high-fat high-carbohydrate diet (HFHC)-induced obesity and NASH murine model. Results We uncovered activation of mTORC1 signaling cascade and specific reduction in cytolytic natural killer T (NKT) cells, which subsequently enhanced tumor growth of orthotopically-implanted HCC tumor cells. Notably, treatment of the mTORC1/C2 dual kinase inhibitor vistusertib (AZD2014), currently undergone phase I/II clinical trials, not only abrogated mTORC1/SREBP2 signaling and cholesterol levels, but also derepressed the cytolytic NKT cells in blood and liver leading to reduced tumorigenicity. Furthermore, NKT cells inactivation by a specific antibody targeting the CD1d receptor abolished anti-tumor effects of vistusertib. Conclusions Collectively, this study elucidates the metabolic-immunosuppressive role of mTOR signaling in NAFLD-associated HCC and provides insights into the development of therapeutic strategies against the mTOR-reinforced NAFLD-associated HCC. This project is supported by Collaborative Research Fund (C4045–18W) and the AstraZeneca Preclinical Oncology Research Program (2017).","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121859874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IDDF2019-ABS-0160 Cathepsin C promotes tumor growth and metastasis through activating TNF-α/MAPK (p38) pathway in hepatocellular carcinoma","authors":"Guopei Zhang, Xiao Yue, Shao-Qiang Li","doi":"10.1136/gutjnl-2019-iddfabstracts.98","DOIUrl":"https://doi.org/10.1136/gutjnl-2019-iddfabstracts.98","url":null,"abstract":"Background Although cathepsin C (CTSC), a multifunctional molecule, has been reported to maintain various malignant biological properties in several types of cancers, the potential function of CTSC in HCC remains obscure. We aimed to investigate the potential role of cathepsin C (CTSC) in the tumorigenesis of HCC. Methods One hundred and twenty-two HCC specimens upon tissue microarrays were employed to analyze the correlation between CTSC expression and clinicopathological characteristics through immunohistochemistry staining. qRT-PCR, western blot assay, CCK-8 assay, colony formation, cell migration and invasion assays, xenograft mice model were adopted to validate what had been indicated by the bioinformatic web tools. Results In our study, by the bioinformatic tools and tissue microarrays, CTSC was found upregulated in HCC compared with normal liver tissues, and its higher expression was correlated with poor prognosis of HCC patients. By gain-of-function and loss-of-function studies, we implicated that CTSC functioned as an oncogene to promote the proliferation, migration and invasion of HCC cells. Mechanistically, we revealed that CTSC was involved in several cancer-related signaling pathways by Gene Set Enrichment Analysis (GSEA), among which TNF-α/p38 pathway was verified to be activated by CTSC. Furthermore, we found that TNF-α could activate CTSC expression in a concentration-dependent manner. Ralimetinib, an oral MAPK (p38) inhibitor could inhibit CTSC expression. These indicated a potential positive feedback loop between CTSC and TNF-α/MAPK (p38) signaling. Conclusions Taken together, CTSC plays an important role in the growth and metastasis of HCC and may be a promising therapeutic target upon HCC.","PeriodicalId":261851,"journal":{"name":"Basic Hepatology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129606497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}