Livers Pub Date : 2023-07-04 DOI: 10.3390/livers3030024

Nicholas Noverati, V. Yan, Jay W. Jun, D. Halegoua-DeMarzio, H. Hann

引用次数: 0

Special Issue “Liver Fibrosis: Mechanisms, Targets, Assessment and Treatment” 特刊《肝纤维化:机制、靶点、评估与治疗》

Livers Pub Date : 2023-06-27 DOI: 10.3390/livers3030023

R. Weiskirchen, T. Sauerbruch

引用次数: 0

Regeneration and Recovery after Acetaminophen Hepatotoxicity. 对乙酰氨基酚肝毒性后的再生与恢复。

Livers Pub Date : 2023-06-01 DOI: 10.3390/livers3020021

Bharat Bhushan, Udayan Apte

{"title":"Regeneration and Recovery after Acetaminophen Hepatotoxicity.","authors":"Bharat Bhushan, Udayan Apte","doi":"10.3390/livers3020021","DOIUrl":"https://doi.org/10.3390/livers3020021","url":null,"abstract":"Liver regeneration is a compensatory response to tissue injury and loss. It is known that liver regeneration plays a crucial role in recovery following acetaminophen (APAP)-induced hepatotoxicity, which is the major cause of acute liver failure (ALF) in the US. Regeneration increases proportional to the extent of liver injury upon APAP overdose, ultimately leading to regression of injury and spontaneous recovery in most cases. However, severe APAP overdose results in impaired liver regeneration and unchecked progression of liver injury, leading to failed recovery and mortality. Inter-communication between various cell types in the liver is important for effective regenerative response following APAP hepatotoxicity. Various non-parenchymal cells such macrophages, stellate cells, and endothelial cells produce mediators crucial for proliferation of hepatocytes. Liver regeneration is orchestrated by synchronized actions of several proliferative signaling pathways involving numerous kinases, nuclear receptors, transcription factors, transcriptional co-activators, which are activated by cytokines, growth factors, and endobiotics. Overt activation of anti-proliferative signaling pathways causes cell-cycle arrest and impaired liver regeneration after severe APAP overdose. Stimulating liver regeneration by activating proliferating signaling and suppressing anti-proliferative signaling in liver can prove to be important in developing novel therapeutics for APAP-induced ALF.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"3 2","pages":"300-309"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10426764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10017108","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

The role of cytochrome P450 3A4-mediated metabolism in sorafenib and lapatinib hepatotoxicity. 细胞色素P4503A4介导的代谢在索拉非尼和拉帕替尼肝毒性中的作用

Livers Pub Date : 2023-06-01 Epub Date: 2023-06-19 DOI: 10.3390/livers3020022

Mitchell R McGill, Yihong J Kaufman, Francesca V LoBianco, Mary A Schleiff, Nukhet Aykin-Burns, Grover P Miller

{"title":"The role of cytochrome P450 3A4-mediated metabolism in sorafenib and lapatinib hepatotoxicity.","authors":"Mitchell R McGill, Yihong J Kaufman, Francesca V LoBianco, Mary A Schleiff, Nukhet Aykin-Burns, Grover P Miller","doi":"10.3390/livers3020022","DOIUrl":"10.3390/livers3020022","url":null,"abstract":"Tyrosine kinase inhibitors (TKIs) are increasingly popular drugs used to treat more than a dozen different diseases, including some forms of cancer. Despite having fewer adverse effects than traditional chemotherapies, they are not without risks. Liver injury is a particular concern. Of the FDA-approved TKIs, approximately 40% cause hepatotoxicity. However, little is known about the underlying pathophysiology. The leading hypothesis is that TKIs are converted by cytochrome P450 3A4 (CYP3A4) to reactive metabolites that damage proteins. Indeed, there is strong evidence for this bioactivation of TKIs in in vitro reactions. However, the actual toxic effects are underexplored. Here, we measured the cytotoxicity of several TKIs in primary mouse hepatocytes, HepaRG cells, and HepG2 cells with and without CYP3A4 modulation. To our surprise, the data indicate that CYP3A4 increases resistance to sorafenib and lapatinib hepatotoxicity. The results have implications for the mechanism of toxicity of these drugs in patients and underline the importance of selecting an appropriate experimental model.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":"310-321"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48636302","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

Mitochondria in Acetaminophen-Induced Liver Injury and Recovery: A Concise Review. 线粒体在对乙酰氨基酚诱导的肝损伤及其恢复中的作用:简要综述。

Livers Pub Date : 2023-06-01 DOI: 10.3390/livers3020014

Anup Ramachandran, Hartmut Jaeschke

{"title":"Mitochondria in Acetaminophen-Induced Liver Injury and Recovery: A Concise Review.","authors":"Anup Ramachandran, Hartmut Jaeschke","doi":"10.3390/livers3020014","DOIUrl":"https://doi.org/10.3390/livers3020014","url":null,"abstract":"Mitochondria are critical organelles responsible for the maintenance of cellular energy homeostasis. Thus, their dysfunction can have severe consequences in cells responsible for energy-intensive metabolic function, such as hepatocytes. Extensive research over the last decades have identified compromised mitochondrial function as a central feature in the pathophysiology of liver injury induced by an acetaminophen (APAP) overdose, the most common cause of acute liver failure in the United States. While hepatocyte mitochondrial oxidative and nitrosative stress coupled with induction of the mitochondrial permeability transition are well recognized after an APAP overdose, recent studies have revealed additional details about the organelle’s role in APAP pathophysiology. This concise review highlights these new advances, which establish the central role of the mitochondria in APAP pathophysiology, and places them in the context of earlier information in the literature. Adaptive alterations in mitochondrial morphology as well as the role of cellular iron in mitochondrial dysfunction and the organelle’s importance in liver recovery after APAP-induced injury will be discussed.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"3 2","pages":"219-231"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9781815","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: 2

Book Review: Weiskirchen, R.; Friedman, S.L. Hepatic Stellate Cells: Methods and Protocols, 1st Ed.; Weiskirchen, R., Friedman, S.L., Eds.; Methods in Molecular Biology 2669; Humana Press: New York, NY, USA, 2023; ISBN 978-1-07-163206-2; eISBN: 978-1-0716-3207-9 书评：Weiskirchen，R。；Friedman，S.L.《肝星状细胞：方法和方案》，第1版。；Weiskirchen，R.，Friedman，S.L.，编辑。；分子生物学方法2669；Humana出版社：美国纽约州纽约市，2023年；ISBN 978-1-07-163206-2；eISBN:978-1-0716-3207-9

Livers Pub Date : 2023-05-29 DOI: 10.3390/livers3020020

R. Weiskirchen, S. Friedman

引用次数: 0

Expression of Bone Morphogenetic Protein 14 in Liver Disease and Cancer 骨形态发生蛋白14在肝病和癌症中的表达

Livers Pub Date : 2023-05-25 DOI: 10.3390/livers3020019

J. Sommer, W. Thasler, A. Bosserhoff, C. Hellerbrand

{"title":"Expression of Bone Morphogenetic Protein 14 in Liver Disease and Cancer","authors":"J. Sommer, W. Thasler, A. Bosserhoff, C. Hellerbrand","doi":"10.3390/livers3020019","DOIUrl":"https://doi.org/10.3390/livers3020019","url":null,"abstract":"The activation of hepatic stellate cells (HSCs) is the key event of hepatic fibrosis. Furthermore, activated HSCs also play an important role in the progression of hepatocellular cancer (HCC). Bone morphogenetic protein 14 (BMP14) is a member of the TGF-β/BMP superfamily. So far, most studies have analyzed BMP14 in the context of bone and cartilage formation and homeostasis. The aim of this study was to assess the expression and function of BMP14 in liver fibrosis and HCC. The BMP14 expression increased during the in vitro activation of primary human HSCs and also in mouse models of liver fibrosis. In human HCC, as well as non-tumorous liver tissues, there was a significant correlation between the expression of BMP14 and alpha-smooth-muscle actin (α-SMA), an established marker for HSC activation. RNAi-mediated BMP14 suppression in activated HSCs resulted in the reduced expression of the transcription factors inhibitor of differentiation 1 (ID1) and ID2, known targets of BMP signaling. Interestingly, α-SMA and collagen expression was also reduced in BMP14-depleted cells, while treatment with recombinant BMP14 induced ID1, ID2, α-SMA and collagen expression. In human HCC cell lines, treatment with recombinant BMP14 induced proliferation, migratory activity and colony formation. In summary, our data indicate activated HSCs as a major cellular source of enhanced BMP14 expression in fibrotic liver disease and HCC, and show that BMP14 exhibits pro-fibrogenic as well as pro-tumorigenic effects. Future analyses will reveal the potential of this soluble growth factor as a therapeutic target or prognostic marker for the progression of fibrosis and HCC in patients with chronic liver disease.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43502372","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

Prevalence and Trends in Hepatitis B & C Virus among Blood Donors in Pakistan: A Regional Transfusion Center Study 巴基斯坦献血者中乙型和丙型肝炎病毒的流行率和趋势：一项区域输血中心的研究

Livers Pub Date : 2023-05-17 DOI: 10.3390/livers3020018

Tehreem Zorob, Muhammad-Awais Farooqi, A. Ahsan, Abdullah Zaki, M. Rathore, H. Farooqi

{"title":"Prevalence and Trends in Hepatitis B & C Virus among Blood Donors in Pakistan: A Regional Transfusion Center Study","authors":"Tehreem Zorob, Muhammad-Awais Farooqi, A. Ahsan, Abdullah Zaki, M. Rathore, H. Farooqi","doi":"10.3390/livers3020018","DOIUrl":"https://doi.org/10.3390/livers3020018","url":null,"abstract":"Around 118.5 million blood donations are collected annually to save precious lives. The donated blood may also be associated with blood-borne infections. With around 247 million population, Pakistan is an endemic country for viral hepatitis, and there is a high risk of having asymptomatic blood donors among healthy donors. Viral hepatitis is 2.5% prevalent in the general population, and blood donation and its screening have become grave health concerns for Pakistani health authorities. Asymptomatic viral hepatitis needs screening to rule out subliminally diseased individuals, as recommended by the World Health Organization. Knowing the prevalence of the transfusion transmissible infectious (TTIs) agents in healthy blood donors helps assess the disease burden in any population, boosts treatment rates, and precludes dreaded complications in the affected people. The objective of the current study was to determine the prevalence and trends of significant TTIs among blood donors visiting the Armed Forces Institute of Transfusion (AFIT), Rawalpindi, Pakistan. A total of 15,405 blood donors were screened for HBV, HCV, HIV, malaria, and syphilis during this cross-sectional descriptive study. Most donors had an O-positive blood group; AB-negative donors were only 0.7%. Out of the study population, we reported 1.06% HBV, 0.54% HCV, 0.19% HIV, and 0.31% syphilis-positive asymptomatic blood donors. However, no blood donor was found positive for malaria. The Punjab province was reported as the most burdened for TTIs, and youngsters aged 18–27 years were mainly positive, indicating the need to conduct national-level awareness campaigns about TTIs. The stakeholders need to strengthen the blood collection guidelines, and effective performance should be strictly monitored through internal and external audits considering the aim of reaching non-infectious blood products.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48031859","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

Effect of Bergamot Leaves (Citrus bergamia) in the Crosstalk between Adipose Tissue and Liver of Diet-Induced Obese Rats 佛手柑叶对饮食诱导肥胖大鼠脂肪组织与肝脏串扰的影响

Livers Pub Date : 2023-05-11 DOI: 10.3390/livers3020017

J. S. Siqueira, Erika Tiemi Nakandakare-Maia, T. A. Vieira, T. Palacio, N. A. Grandini, M. Belin, G. A. Nai, F. Moreto, A. Altomare, G. Baron, G. Aldini, F. V. Francisqueti-Ferron, C. Corrêa

{"title":"Effect of Bergamot Leaves (Citrus bergamia) in the Crosstalk between Adipose Tissue and Liver of Diet-Induced Obese Rats","authors":"J. S. Siqueira, Erika Tiemi Nakandakare-Maia, T. A. Vieira, T. Palacio, N. A. Grandini, M. Belin, G. A. Nai, F. Moreto, A. Altomare, G. Baron, G. Aldini, F. V. Francisqueti-Ferron, C. Corrêa","doi":"10.3390/livers3020017","DOIUrl":"https://doi.org/10.3390/livers3020017","url":null,"abstract":"The excessive consumption of diets rich in sugar and fat is associated with metabolic manifestations involving adipose tissue and the liver. Bergamot, due to its antioxidant and anti-inflammatory properties, has been used to treat metabolic disorders. This work aimed to verify the effect of Bergamot leaves extract (BLE) on the crosstalk in the adipose tissue–liver axis of obese rats. For 20 weeks, Wistar rats were distributed into two groups: control (Control) and high sugar–fat (HSF) diet groups. Afterwards, the animals were redistributed into three groups for 10 weeks: control diet + vehicle (Control, n = 08), HSF + vehicle (HSF, n = 08), and HSF + BLE (HSF + BLE, n = 08). The BLE was carried out daily by gavage (50 mg/kg). The HSF group presented obesity, hyperglycemia, hypertriglyceridemia, insulin resistance, hepatic microvesicular steatosis, higher inflammation and oxidative stress in the liver and adipose tissue. In comparison to the HSF group, HSF + BLE animals showed protection by reducing the triglyceride levels, insulin resistance, inflammation and oxidative stress in hepatic and adipose tissues. BLE acted on the inflammation and oxidative stress in the adipose tissue–liver axis in obese rats when compared to the HSF group, which may have reflected on the improvement of insulin resistance and dyslipidemia.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43279664","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

Peritoneal Immunity in Liver Disease 肝脏疾病的腹膜免疫

Livers Pub Date : 2023-04-26 DOI: 10.3390/livers3020016

Joseph Delo, D. Forton, E. Triantafyllou, A. Singanayagam

引用次数: 0

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