Livers Pub Date : 2022-12-01 DOI: 10.3390/livers2040030

Chuan-Yi Lin, May-Hua Liao, Chi-Yu Yang, Chao-Kai Chang, Shih-Mei Hsu, C. Juang, H. Wen

{"title":"Anti-Metastatic Activity of Tagitinin C from Tithonia diversifolia in a Xenograft Mouse Model of Hepatocellular Carcinoma","authors":"Chuan-Yi Lin, May-Hua Liao, Chi-Yu Yang, Chao-Kai Chang, Shih-Mei Hsu, C. Juang, H. Wen","doi":"10.3390/livers2040030","DOIUrl":"https://doi.org/10.3390/livers2040030","url":null,"abstract":"Sesquiterpenoid tagitinin C, present in Tithonia diversifolia leaves, has been known to have anti-hepatoma properties. Therefore, we investigated the anti-metastatic potential of tagitinin C in xenograft models of hepatocellular carcinoma (HCC). We isolated tagitinin C from a methanolic extract of the leaves of T. diversifolia. HepG-2 and Huh 7 hepatoma cells were treated with tagitinin C, and cell viability, migration, and matrix metalloproteinase (MPP) activity were assessed using the 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyltetrazolium bromide assay, scratch migration assay, and MMP activity assay, respectively. We used magnetic resonance spectroscopy to determine the tumorigenicity of xenografts inoculated with Hep-G2 and Huh 7 cells. Tagitinin C was cytotoxic against Hep-G2 and Huh 7 cells, with IC50 values of 2.0 ± 0.1 µg/mL and 1.2 ± 0.1 µg/mL, respectively, and it showed an anti-metastatic effect in vitro. Additionally, MRS assays revealed that tagitinin C (15 g/mouse/day) reduced the tumorigenicity of Hep-G2 and Huh 7 cell xenografts. Tagitinin C demonstrated significant antitumor and anti-metastatic activity in the two human hepatoma cell lines. Tagitinin C might be used as an alternative or auxiliary therapy for the treatment of HCC, and its effect should be further investigated in clinical settings.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41611491","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}

引用次数: 1

Role of Pyroptosis in Acetaminophen-Induced Hepatotoxicity. 对乙酰氨基酚诱导的肝毒性中的热蛋白沉积作用

Livers Pub Date : 2022-12-01 Epub Date: 2022-12-13 DOI: 10.3390/livers2040032

Hartmut Jaeschke, David S Umbaugh, Anup Ramachandran

{"title":"Role of Pyroptosis in Acetaminophen-Induced Hepatotoxicity.","authors":"Hartmut Jaeschke, David S Umbaugh, Anup Ramachandran","doi":"10.3390/livers2040032","DOIUrl":"10.3390/livers2040032","url":null,"abstract":"<p><p>Acetaminophen (APAP) is a widely used pain reliever that can cause liver injury or liver failure in response to an overdose. Understanding the mechanisms of APAP-induced cell death is critical for identifying new therapeutic targets. In this respect it was hypothesized that hepatocytes die by oncotic necrosis, apoptosis, necroptosis, ferroptosis and more recently pyroptosis. The latter cell death is characterized by caspase-dependent gasdermin cleavage into a C-terminal and an N-terminal fragment, which forms pores in the plasma membrane. The gasdermin pores can release potassium, interleukin-1β (IL-1β), IL-18, and other small molecules in a sublytic phase, which can be the main function of the pores in certain cell types such as inflammatory cells. Alternatively, the process can progress to full lysis of the cell (pyroptosis) with extensive cell contents release. This review discusses the experimental evidence for the involvement of pyroptosis in APAP hepatotoxicity as well as the arguments against pyroptosis as a relevant mechanism of APAP-induced cell death in hepatocytes. Based on the critical evaluation of the currently available literature and understanding of the pathophysiology, it can be concluded that pyroptotic cell death is unlikely to be a relevant contributor to APAP-induced liver injury.</p>","PeriodicalId":74083,"journal":{"name":"Livers","volume":"2 4","pages":"425-435"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9802630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10480188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Preclinical Experience of the Mayo Spheroid Reservoir Bioartificial Liver (SRBAL) in Management of Acute Liver Failure Mayo球形贮存器生物人工肝（SRBAL）治疗急性肝功能衰竭的临床前经验

Livers Pub Date : 2022-11-02 DOI: 10.3390/livers2040029

P. Felgendreff, Mohammad Tharwat, Seyed M. Hosseiniasl, B. Amiot, Anna Minshew, A. A. Rmilah, Xiaoye Sun, Dustin J. Duffy, W. Kremers, S. Nyberg

{"title":"Preclinical Experience of the Mayo Spheroid Reservoir Bioartificial Liver (SRBAL) in Management of Acute Liver Failure","authors":"P. Felgendreff, Mohammad Tharwat, Seyed M. Hosseiniasl, B. Amiot, Anna Minshew, A. A. Rmilah, Xiaoye Sun, Dustin J. Duffy, W. Kremers, S. Nyberg","doi":"10.3390/livers2040029","DOIUrl":"https://doi.org/10.3390/livers2040029","url":null,"abstract":"The Spheroid Reservoir Bioartificial Liver (SRBAL) is an innovative treatment option for acute liver failure (ALF). This extracorporeal support device, which provides detoxification and other liver functions using high-density culture of porcine hepatocyte spheroids, has been reported in three randomized large animal studies. A meta-analysis of these three preclinical studies was performed to establish efficacy of SRBAL treatment in terms of survival benefit and neuroprotective effect. The studies included two hepatotoxic drug models of ALF (D-galactosamine, α-amanitin/lipopolysaccharide) or a liver resection model (85% hepatectomy) in pigs or monkeys. The SRBAL treatment was started in three different settings starting at 12 h, 24 h or 48 h after induction of ALF; comparisons were made with two similar control groups in each model. SRBAL therapy was associated with significant survival and neuroprotective benefits in all three animal models of ALF. The benefits of therapy were dose dependent with the most effective configuration of SRBAL being continuous treatment of 24 h duration and dose of 200 g of porcine hepatic spheroids. Future clinical testing of SRBAL in patients with ALF appears warranted.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44158276","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}

引用次数: 0

FYB2 Is a Potential Prognostic Biomarker for Hepatocellular Carcinoma FYB2是肝细胞癌的潜在预后生物标志物

Livers Pub Date : 2022-11-02 DOI: 10.3390/livers2040027

Yifang Qu, X. Shen, Xinpei Yuan, Bing Lu

{"title":"FYB2 Is a Potential Prognostic Biomarker for Hepatocellular Carcinoma","authors":"Yifang Qu, X. Shen, Xinpei Yuan, Bing Lu","doi":"10.3390/livers2040027","DOIUrl":"https://doi.org/10.3390/livers2040027","url":null,"abstract":"FYB2 (also known as C1orf168 or ARAP) is an adaptor protein involved in T-cell receptor (TCR)-mediated T-cell activation and adhesion. However, the correlation of FYB2 with prognosis and cancer needs further investigation. In this study, we analyzed the expression levels of FYB2 in hepatocellular carcinoma (LIHC) tumor tissues and correlated it with the pathological stages, survival outcomes, and tumor grades. We found that the expression of FYB2 was significantly downregulated in LIHC. Low FYB2 level leading to weak survival outcomes is linked with advanced tumor grades and elevated pathological stages. Cox regression analysis showed that FYB2 and AJCC-M stages can be used as independent prognostic factors for LIHC. GSEA analysis revealed that FYB2 would be notably correlated with the cellular metabolism-related pathways and particularly involved in the regulation of cancer-related pathways. Single-cell transcriptome analysis revealed that FYB2-positive cells were mainly distributed in hepatocytes, and compared with other cells, the upregulated genes of these cells were mainly enriched in metabolism-related functions. The results of the spatial transcriptome revealed that the expression of FYB2 in the adjacent area was higher than in the tumor area. These results showed that FYB2 is likely to be a new prognostic biomarker in LIHC and would help provide individual treatment decisions for LIHC patients.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44767772","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}

引用次数: 0

Liver Fibrosis, Liver Cancer, and Advances in Therapeutic Approaches 肝纤维化、肝癌及治疗方法的进展

Livers Pub Date : 2022-11-02 DOI: 10.3390/livers2040028

Indu G. Rajapaksha

引用次数: 1

Synergistic Anti-tumor Effect of Palmitoylcarnitine and Dasatinib in Liver Cancer 棕榈酰肉碱和达沙替尼对癌症的协同抗肿瘤作用

Livers Pub Date : 2022-11-01 DOI: 10.3390/livers2040026

Ragini Singh, Shu-Li Cheng, Qinghua Zeng, Santosh Kumar, Carlos Marques

{"title":"Synergistic Anti-tumor Effect of Palmitoylcarnitine and Dasatinib in Liver Cancer","authors":"Ragini Singh, Shu-Li Cheng, Qinghua Zeng, Santosh Kumar, Carlos Marques","doi":"10.3390/livers2040026","DOIUrl":"https://doi.org/10.3390/livers2040026","url":null,"abstract":"Hepatocellular carcinoma (HCC) is the third major cause of cancer-related death worldwide and responds positively to tyrosine kinase inhibitors (TKIs). Dasatinib (Das) is an Src/Abl family kinase and has been successfully utilized in the treatment of various cancers. Cancer cells are known to limit their oxidative phosphorylation to minimize oxidative stress. Palmitoylcarnitine (Pcar) incubation triggers mitochondria-mediated apoptosis in cancer cells by increasing the mitochondrial respiration rate. It stimulates the H2O2 production in cancer cells and thus induces oxidative stress. Thus, considering the above observations, the combined effect of Pcar and Das on HepG2, liver cancer cells has been evaluated in the present study. Results demonstrated that combined exposure to Pcar and dasatinib inhibited cell growth, proliferation, and invasion efficiency of cancerous cells more than single-drug treatment. Further, cells undergo membrane depolarization and caspase-dependent apoptosis upon exposure to combined treatment. In addition, in vivo study showed that Pcar and dasatinib treatment reduced the tumor size in mice more significantly than single-drug treatment. Thus, considering the above remarks, combined therapy of Pcar and dasatinib may serve as a potential candidate in the treatment of liver cancer in human and animal tissues.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47434927","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}

引用次数: 0

Is There a Place for Somatostatin Analogues for the Systemic Treatment of Hepatocellular Carcinoma in the Immunotherapy Era? 在免疫治疗时代，生长抑素类似物在肝细胞癌的全身治疗中有一席之地吗?

Livers Pub Date : 2022-10-18 DOI: 10.3390/livers2040024

E. Kouroumalis, Ioannis Tsomidis, A. Voumvouraki

{"title":"Is There a Place for Somatostatin Analogues for the Systemic Treatment of Hepatocellular Carcinoma in the Immunotherapy Era?","authors":"E. Kouroumalis, Ioannis Tsomidis, A. Voumvouraki","doi":"10.3390/livers2040024","DOIUrl":"https://doi.org/10.3390/livers2040024","url":null,"abstract":"Patients with advanced hepatocellular carcinoma (HCC) have a very limited survival rate even after the recent inclusion of kinase inhibitors or immune checkpoint inhibitors in the therapeutic armamentarium. A significant problem with the current proposed therapies is the considerable cost of treatment that may be a serious obstacle in low- and middle-income countries. Implementation of somatostatin analogues (SSAs) has the potential to overcome this obstacle, but due to some negative studies their extensive evaluation came to a halt. However, experimental evidence, both in vitro and in vivo, has revealed various mechanisms of the anti-tumor effects of these analogues, including inhibition of cancer cell proliferation and angiogenesis and induction of apoptosis. Favorable indirect effects such as inhibition of liver inflammation and fibrosis and influence on macrophage-mediated innate immunity have also been noted and are presented in this review. Furthermore, the clinical application of SSAs is both presented and compared with clinical trials of kinase and immune checkpoint inhibitors (ICIs). No direct trials have been performed to compare survival in the same cohort of patients, but the cost of treatment with SSAs is a fraction compared to the other modalities and with significantly less serious side effects. As in immunotherapy, patients with viral HCC (excluding alcoholics), as well as Barcelona stage B or C and Child A patients, are the best candidates, since they usually have a survival prospect of at least 6 months, necessary for optimum results. Reasons for treatment failures are also discussed and further research is proposed.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45566965","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}

引用次数: 1

Role of Oxidative Stress in Liver Disorders 氧化应激在肝脏疾病中的作用

Livers Pub Date : 2022-10-14 DOI: 10.3390/livers2040023

L. Conde de la Rosa, Leire Goicoechea, S. Torres, C. Garcia-Ruiz, J. Fernandez-Checa

{"title":"Role of Oxidative Stress in Liver Disorders","authors":"L. Conde de la Rosa, Leire Goicoechea, S. Torres, C. Garcia-Ruiz, J. Fernandez-Checa","doi":"10.3390/livers2040023","DOIUrl":"https://doi.org/10.3390/livers2040023","url":null,"abstract":"Oxygen is vital for life as it is required for many different enzymatic reactions involved in intermediate metabolism and xenobiotic biotransformation. Moreover, oxygen consumption in the electron transport chain of mitochondria is used to drive the synthesis of ATP to meet the energetic demands of cells. However, toxic free radicals are generated as byproducts of molecular oxygen consumption. Oxidative stress ensues not only when the production of reactive oxygen species (ROS) exceeds the endogenous antioxidant defense mechanism of cells, but it can also occur as a consequence of an unbalance between antioxidant strategies. Given the important role of hepatocytes in the biotransformation and metabolism of xenobiotics, ROS production represents a critical event in liver physiology, and increasing evidence suggests that oxidative stress contributes to the development of many liver diseases. The present review, which is part of the special issue “Oxidant stress in Liver Diseases”, aims to provide an overview of the sources and targets of ROS in different liver diseases and highlights the pivotal role of oxidative stress in cell death. In addition, current antioxidant therapies as treatment options for such disorders and their limitations for future trial design are discussed.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44904998","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}

引用次数: 19

Risk Prevention and Health Promotion for Non-Alcoholic Fatty Liver Diseases (NAFLD) 非酒精性脂肪肝的风险预防和健康促进

Livers Pub Date : 2022-10-09 DOI: 10.3390/livers2040022

Adnan Khan, H. M. Ross, N. Parra, Sarah L. Chen, Kashyap Chauhan, Makala Wang, Binghai Yan, John Magagna, Jake Beiriger, Y. Shah, Taha Shahzad, D. Halegoua-DeMarzio

引用次数: 3

Alagille Syndrome and Its Clinical and Laboratory Features: A Case Report Alagille综合征及其临床和实验室特征1例报告

Livers Pub Date : 2022-10-09 DOI: 10.3390/livers2040021

L. Abenavoli, L. Boccuto, A. Corea, M. Gambardella, R. Spagnuolo, F. Luzza

引用次数: 0

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