Liver Research最新文献

{"title":"Chinese expert consensus on the clinical application of molecular diagnostics in hepatobiliary cancers (2024 edition)","authors":"Aizier Ainiwaer ,&nbsp;Jiamin Cheng ,&nbsp;Ren Lang ,&nbsp;Tao Peng ,&nbsp;Xinyu Bi ,&nbsp;Yinying Lu ,&nbsp;Chinese Research Hospital Association Society for Molecular Diagnosis,&nbsp;Translational Medicine Branch, China Association of Gerontology and Geriatrics","doi":"10.1016/j.livres.2024.11.005","DOIUrl":"10.1016/j.livres.2024.11.005","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) are significant health challenges in China because of their high prevalence and mortality rates. Advances in molecular diagnostics have opened new avenues for personalized treatment strategies. This consensus provides a comprehensive update on the clinical applications of molecular diagnostics in HCC and BTC and addresses the urgent need for personalized treatment strategies tailored to the Chinese population, emphasizing the importance of molecular markers in guiding targeted therapies and immunotherapies. By employing the Delphi method and the Grading of Recommendations Assessment, Development, and Evaluation system, the expert panel formulated evidence-based recommendations for the use of molecular diagnostics in the clinical management of HCC and BTC. Key molecular markers, such as isocitrate dehydrogenase (IDH) 1 and 2, fibroblast growth factor receptor 2 (FGFR2), BRAF V600E, human epidermal growth factor receptor 2 (HER2), rearranged during transfection (RET), and neurotrophic tyrosine receptor kinase (NTRK), are highlighted for their roles in optimizing treatment regimens. The consensus also explores the significance of emerging biomarkers, such as tumor mutation burden and microsatellite instability, in predicting responses to immune checkpoint inhibitors. The recommendations aim to enhance precision medicine approaches, improve patient outcomes, and foster the integration of molecular diagnostics into routine clinical practice.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"8 4","pages":"Pages 195-206"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143322648","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}

{"title":"Growth differentiation factor 7 alleviates the proliferation and metastasis of hepatocellular carcinoma","authors":"Jianyong Zhuo ,&nbsp;Huigang Li ,&nbsp;Peiru Zhang ,&nbsp;Chiyu He ,&nbsp;Wei Shen ,&nbsp;Xinyu Yang ,&nbsp;Zuyuan Lin ,&nbsp;Runzhou Zhuang ,&nbsp;Xuyong Wei ,&nbsp;Shusen Zheng ,&nbsp;Xiao Xu ,&nbsp;Di Lu","doi":"10.1016/j.livres.2024.09.006","DOIUrl":"10.1016/j.livres.2024.09.006","url":null,"abstract":"<div><h3>Background and aims</h3><div>Inflammatory factors play significant roles in the development and occurrence of hepatocellular carcinoma (HCC). However, the tumor-protective functions of growth differentiation factors (GDFs) in HCC are yet to be clarified. In this study, we aimed to evaluate the expression levels of 10 GDFs in tumor and paratumor tissues from patients with HCC and perform <em>in vitro</em> and <em>in vivo</em> experiments to elucidate the role of GDF7 in regulating the proliferation and metastasis of HCC.</div></div><div><h3>Methods</h3><div>The gene expression of 10 GDFs was compared between HCC and paratumors using The Cancer Genome Atlas dataset and patient-derived tissues. A tumor microarray containing 108 HCC tissue samples was used to explore the prognostic value of GDF7 expression. Loss-of-function experiments were also performed <em>in vitro</em> and <em>in vivo</em> to investigate the role of GDF7 in HCC.</div></div><div><h3>Results</h3><div>The mRNA and protein levels of GDF7 were significantly lower in HCC tumors than in paratumors (<em>P</em> &lt; 0.001). Kaplan–Meier analysis showed that decreased GDF7 expression in HCC was associated with worse overall survival (5-year rate: 61.8% <em>vs</em>. 27.5%, <em>P</em> &lt; 0.001) and increased recurrence risk (<em>P</em> &lt; 0.001). Multivariate Cox regression analysis demonstrated that low GDF7 expression, the presence of microvascular invasion, and elevated alpha-fetoprotein (AFP) levels were independent risk factors for tumor recurrence and poor survival. Downregulation of GDF7 also increased the tumor growth in HCC cells and in an HCC xenograft model. GDF7 knockdown promoted migration and invasion via epithelial–mesenchymal transition. Meanwhile, a negative correlation between JunB proto-oncogene (JUNB) and GDF7 was observed in HCC tissues. Modulating JUNB levels altered GDF7 protein expression.</div></div><div><h3>Conclusions</h3><div>GDF7 is a potential biomarker for predicting superior outcomes in patients with HCC. GDF7 amplification is a potential therapeutic option for HCC.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"8 4","pages":"Pages 259-268"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143356750","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}

{"title":"Chinese clinical practice guidelines for pediatric split liver transplantation","authors":"Binsheng Fu ,&nbsp;Xiao Feng ,&nbsp;Jianrong Liu ,&nbsp;Jie Ren ,&nbsp;Jin Wang ,&nbsp;Shuhong Yi ,&nbsp;Yang Yang ,&nbsp;Chinese Society of Organ Transplantation of Chinese Medical Association,&nbsp;Surgery Group of Chinese Society of Surgery of Chinese Medical Association,&nbsp;Transplantation Group of Chinese Society of Surgery of Chinese Medical Association,&nbsp;South China Alliance of Split Liver Transplantation","doi":"10.1016/j.livres.2024.11.002","DOIUrl":"10.1016/j.livres.2024.11.002","url":null,"abstract":"<div><div>Liver transplantation is an effective treatment for end-stage liver disease in children, and its clinical efficacy has been validated. Split liver transplantation (SLT) can effectively expand the donor liver pool for children. SLT for children has unique clinical characteristics and principles. Establishing technical operation specifications for pediatric SLT plays a significant role in improving clinical efficacy. In this paper, clinical practice guidelines on pediatric SLT were established in the aspect of donor and donor liver evaluation, donor-recipient matching, and ductal segmentation and reconstruction of donor liver, aiming to standardize the technical process, optimize surgical operational details, minimize the risk of complications of SLT for children, further promoting the rapid development of pediatric SLT in China.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"8 4","pages":"Pages 207-217"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143323191","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}

{"title":"Current status and new directions for hepatocellular carcinoma diagnosis","authors":"Jinqi Tu ,&nbsp;Bo Wang ,&nbsp;Xiaoming Wang ,&nbsp;Kugeng Huo ,&nbsp;Wanting Hu ,&nbsp;Rongli Zhang ,&nbsp;Jinyao Li ,&nbsp;Shijie Zhu ,&nbsp;Qionglin Liang ,&nbsp;Shuxin Han","doi":"10.1016/j.livres.2024.12.001","DOIUrl":"10.1016/j.livres.2024.12.001","url":null,"abstract":"<div><div>Liver cancer ranks as the sixth most common cancer globally, with hepatocellular carcinoma (HCC) accounting for approximately 75%–85% of cases. Most patients present with moderately advanced disease, while those with advanced HCC face limited and ineffective treatment options. Despite diagnostic efforts, no ideal tumor marker exists to date, highlighting the urgent clinical need for improved early detection of HCC. A key research objective is the development of assays that target specific pathways involved in HCC progression. This review explores the pathological origin and development of HCC, providing insights into the mechanistic rationale, clinical statistics, and the advantages and limitations of commonly used diagnostic tumor markers. Additionally, it discusses the potential of emerging biomarkers for early diagnosis and offers a brief overview of relevant assay methodologies. This review aims to summarize existing markers and investigate new ones, providing a basis for subsequent research.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"8 4","pages":"Pages 218-236"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143323190","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}

{"title":"Single-cell and machine learning approaches uncover intrinsic immune-evasion genes in the prognosis of hepatocellular carcinoma","authors":"Jiani Wang ,&nbsp;Xiaopeng Chen ,&nbsp;Donghao Wu ,&nbsp;Changchang Jia ,&nbsp;Qinghai Lian ,&nbsp;Yuhang Pan ,&nbsp;Jiumei Yang","doi":"10.1016/j.livres.2024.11.001","DOIUrl":"10.1016/j.livres.2024.11.001","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and aims&lt;/h3&gt;&lt;div&gt;Hepatocellular carcinoma (HCC) is a tumor of high heterogeneity and complexity, which poses significant challenges to effective treatment and patient prognosis because of its immune evasion characteristics. To address these issues, single-cell technology and machine learning methods have emerged as a promising approach to identify genes associated with immune escape in HCC. This study aimed to develop a prognostic risk score model for HCC by identifying intrinsic immune-evasion genes (IIEGs) through single-cell technology and machine learning, providing insights into immune infiltration, enhancing predictive accuracy, and facilitating the development of more effective treatment strategies.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;The study utilized data from The Cancer Genome Atlas database to analyze gene expression profiles and clinical data related to intrinsic immune evasion in patients with HCC. Various tools, including the Human Protein Atlas, cBioPortal, single-cell analysis, machine learning, and Kaplan-Meier plot, were used to analyze IIEGs. Functional enrichment analysis was conducted to explore potential mechanisms. In addition, the abundance of infiltrating cells in the tumor microenvironment was investigated using single-sample gene set enrichment analysis, CIBERSORT, xCELL, and tumor immunophenotype algorithms. The expression of glycosylphosphatidylinositol anchor attachment 1 (GPAA1) was examined in the clinical sample of HCC by quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemical staining.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Univariate Cox analysis identified 63 IIEGs associated with the prognosis of HCC. Using random forest, least absolute shrinkage and selection operator regression analysis, and support vector machine, a risk score model consisting of six IIEGs (carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), phosphatidylinositol glycan anchor biosynthesis class U (PIGU), endoplasmic reticulum membrane protein complex subunit 3 (EMC3), centrosomal protein 55 (CEP55), autophagy-related 10 (ATG10), and GPAA1) developed, which was validated using 10 pairs of HCC and adjacent non-cancerous samples. Based on the calculated median risk score, HCC samples were categorized into high- and low-risk groups. The Kaplan-Meier curve analysis showed that the high-risk group had a worse prognosis compared with the low-risk group. Time-dependent receiver operating characteristic analysis demonstrated the accurate predictive capability of the risk score model for HCC prognosis. Furthermore, immune infiltration analysis showed a positive correlation between the risk score model and 40 immune checkpoint genes as well as Th2 cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;A prognostic risk score model was formulated by six IIEG signatures and showed promise in predicting the prognosis of patients diagnosed with HCC. The uti","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"8 4","pages":"Pages 282-294"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143322645","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}

{"title":"Outcome of bariatric surgery in patients with unexpected liver cirrhosis: A multicenter study from China","authors":"Xia Sun ,&nbsp;Libin Yao ,&nbsp;Xing Kang ,&nbsp;Weihua Yu ,&nbsp;Fidele Kakule Kitaghenda ,&nbsp;Mohammad Sajjad Ibn Rashid ,&nbsp;Angeline Nogue Taguemkam ,&nbsp;Jian Hong ,&nbsp;Zhiyong Dong ,&nbsp;Xitai Sun ,&nbsp;Xiaocheng Zhu","doi":"10.1016/j.livres.2024.08.001","DOIUrl":"10.1016/j.livres.2024.08.001","url":null,"abstract":"<div><h3>Background and aims</h3><div>Liver cirrhosis is a complex disease that may result in increased morbidity and mortality following bariatric surgery (BS). This study aimed to explore the outcome of BS in patients with unexpected cirrhosis, focusing on postoperative complications and the progression of liver disease.</div></div><div><h3>Methods</h3><div>A retrospective study of bariatric patients with cirrhosis from four centers in China between 2016 and 2023 was conducted, with follow-up for one year after BS. The primary outcome was the safety of BS in patients with unexpected cirrhosis, while the secondary outcome was the metabolic efficacy of BS in this group postoperatively.</div></div><div><h3>Results</h3><div>A total of 47 patients met the study criteria, including 46 cases of Child-Pugh class A cirrhosis and 1 case of Child-Pugh B. Pathological examination confirmed nodular cirrhosis in 21 patients (44.68%), pseudolobule formation in 1 patient (2.13%), lipedema degeneration with inflammatory cell infiltration in 3 patients (6.38%), and chronic hepatitis in 1 patient (2.13%). The average percentage of total weight loss was 29.73 ± 6.53% at one year postoperatively. During the 30-day postoperative period, the complication rate was 6.38%, which included portal vein thrombosis, gastrointestinal bleeding, and intra-abdominal infection. Moreover, no cases of liver decompensation or mortality were reported during the follow-up period. The remission rates of comorbidities among 41 patients one year after surgery were as follows: dyslipidemia 100%, type 2 diabetes 82.61%, hypertension 84.62%, and obstructive sleep apnea syndrome 85.71%.</div></div><div><h3>Conclusions</h3><div>BS can be safely performed in patients with unexpected cirrhosis in the compensated stage of liver disease, with low postoperative morbidity and no mortality observed during one-year follow-up.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"8 3","pages":"Pages 172-178"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358639","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}

{"title":"Leukocyte cell-derived chemotaxin 2 (LECT2) regulates liver ischemia–reperfusion injury","authors":"Meng-Qi Dong ,&nbsp;Yuan Xie ,&nbsp;Zhi-Liang Tang ,&nbsp;Xue-Wen Zhao ,&nbsp;Fu-Zhen Lin ,&nbsp;Guang-Yu Zhang ,&nbsp;Zhi-Hao Huang ,&nbsp;Zhi-Min Liu ,&nbsp;Yuan Lin ,&nbsp;Feng-Yong Liu ,&nbsp;Wei-Jie Zhou","doi":"10.1016/j.livres.2024.09.004","DOIUrl":"10.1016/j.livres.2024.09.004","url":null,"abstract":"<div><h3>Background and aim</h3><div>Hepatic ischemia–reperfusion injury (IRI) is a significant challenge in liver transplantation, trauma, hypovolemic shock, and hepatectomy, with limited effective interventions available. This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2 (LECT2) in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA (shRNA) delivered through adeno-associated virus (AAV) vectors.</div></div><div><h3>Materials and methods</h3><div>This study analyzed human liver and serum samples from five patients undergoing the Pringle maneuver. <em>Lect2</em>-knockout and C57BL/6J mice were used. Hepatic IRI was induced by clamping the hepatic pedicle. Treatments included recombinant human LECT2 (rLECT2) and AAV-Lect2-shRNA. LECT2 expression levels and serum biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) were measured. Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed.</div></div><div><h3>Results</h3><div>Serum and liver LECT2 levels were elevated during hepatic IRI. Serum LECT2 protein and mRNA levels increased post reperfusion. <em>Lect2</em>-knockout mice had reduced weight loss; hepatic necrosis; and serum ALT, AST, creatinine, and BUN levels. rLECT2 treatment exacerbated weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN). AAV-Lect2-shRNA treatment significantly reduced weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN), indicating therapeutic potential.</div></div><div><h3>Conclusions</h3><div>Elevated LECT2 levels during hepatic IRI increased liver damage. Genetic knockout or shRNA-mediated knockdown of <em>Lect2</em> reduced liver damage, indicating its therapeutic potential. AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI, offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"8 3","pages":"Pages 165-171"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358638","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}

{"title":"Inhaled nitric oxide as a salvage therapy for refractory hypoxemia in the post-transplantation period of hepatopulmonary syndrome: An explorative report of three cases","authors":"Haijin Lyu ,&nbsp;Xiaomeng Yi ,&nbsp;Yunshan Zou ,&nbsp;Pinglan Lu ,&nbsp;Lijuan Li ,&nbsp;Jianrong Liu ,&nbsp;Senbiao Chen ,&nbsp;Xuxia Wei ,&nbsp;Yang Yang ,&nbsp;Huimin Yi","doi":"10.1016/j.livres.2024.09.005","DOIUrl":"10.1016/j.livres.2024.09.005","url":null,"abstract":"<div><div>Liver transplantation (LT) is the only effective treatment for hepatopulmonary syndrome (HPS). Moreover, perioperative refractory hypoxemia (pRH) is a prevalent life-threatening condition and has extremely limited treatment options. Here, we report three patients with HPS who experienced pRH after LT and were consecutively treated with different salvage therapies, ephedrine inhalation, intravenous use of methylene blue with nitric oxide (NO) inhalation, and NO inhalation alone. The results showed that unresolved severe hypoxia may induce fatal morbidity such as early biliary leakage and acute kidney injury. Early initiation of NO inhalation, rather than ephedrine, can significantly improve oxygenation in patients with pRH and may help prevent hypoxia-related complications. Therefore, based on the response to these exploratory salvage treatments, we further demonstrate the unique ventilation-perfusion mismatch pathophysiology in specific lung regions during pRH in HPS. We propose that early inhalation of NO is an important treatment option to rescue severe hypoxia in patients with HPS during the perioperative period of LT.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"8 3","pages":"Pages 188-192"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358543","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}

{"title":"Meldonium-induced steatosis is associated with increased delta 6 desaturation and reduced elongation of n-6 polyunsaturated fatty acids","authors":"Bodil Bjørndal ,&nbsp;Siri Lunde Tungland ,&nbsp;Pavol Bohov ,&nbsp;Magne O. Sydnes ,&nbsp;Simon N. Dankel ,&nbsp;Lise Madsen ,&nbsp;Rolf K Berge","doi":"10.1016/j.livres.2024.09.001","DOIUrl":"10.1016/j.livres.2024.09.001","url":null,"abstract":"<div><h3>Background and objective</h3><div>Metabolic associated fatty liver disease (MAFLD) is associated with abnormal lipid metabolism. Mitochondrial dysfunction is considered an important factor in the onset of MAFLD, whereas altered fatty acid composition has been linked to the severity of the disease. Tetradecylthioacetic acid (TTA), shown to induce mitochondrial proliferation and alter the fatty acid composition, was used to delay the accumulation of hepatic triacylglycerol. This study aimed to evaluate how impaired mitochondrial fatty acid beta-oxidation affects fatty acid composition by incorporating meldonium into a high-carbohydrate diet.</div></div><div><h3>Methods</h3><div>C57BL/6 mice (<em>n</em> = 40) were fed high-carbohydrate diets supplemented with meldonium, TTA, or a combination of meldonium and TTA for 21 days. Lipid levels were determined in liver samples, and fatty acid composition was measured in both liver and plasma samples. Additionally, desaturase and elongase activities were estimated. The hepatic activities and gene expression levels of enzymes involved in fatty acid metabolism were measured in liver samples, whereas carnitines, their precursors, and acylcarnitines were measured in plasma samples.</div></div><div><h3>Results</h3><div>The meldonium-induced depletion of L-carnitine and mitochondrial fatty acid oxidation was confirmed by reduced plasma levels of L-carnitine and acylcarnitines. Principal component analyses of the hepatic fatty acid composition revealed clustering dependent on meldonium and TTA. The meldonium-induced increase in hepatic triacylglycerol levels correlated negatively with estimated activities of elongases and was associated with higher estimated activities of delta-6 desaturase (D6D; C18:4n-3/C18:3n-3 and C18:3n-6/C18:2n-6), and increased circulating levels of C18:4n-3 and C18:3n-6 (gamma-linolenic acid). TTA mitigated meldonium-induced triacylglycerol levels by 80% and attenuated the estimated D6D activities, and elongation of n-6 polyunsaturated fatty acids (PUFAs). TTA also attenuated the meldonium-mediated reduction of C24:1n-9 (nervonic acid), possibly by stimulating <em>Elovl</em><em>5</em> and increased elongation of erucic acid (C22:1n-9) to nervonic acid. The hepatic levels of nervonic acid and the estimated activity of n-6 PUFA elongation correlated negatively with the hepatic triacylglycerol levels, while the estimated activities of D6D correlated positively.</div></div><div><h3>Conclusion</h3><div>Circulating levels of gamma-linolenic acid, along with reduced estimated elongation of n-6 PUFAs and D6D desaturation activities, were associated with hepatic triacylglycerol levels.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"8 3","pages":"Pages 152-164"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358637","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}

{"title":"Genetic engineering drives the breakthrough of pig models in liver disease research","authors":"Chenhao Xu ,&nbsp;Xixi Fang ,&nbsp;Xiao Xu ,&nbsp;Xuyong Wei","doi":"10.1016/j.livres.2024.09.003","DOIUrl":"10.1016/j.livres.2024.09.003","url":null,"abstract":"<div><div>Compared with the widely used rodents, pigs are anatomically, physiologically, and genetically more similar to humans, making them high-quality models for the study of liver diseases. Here, we review the latest research progress on pigs as a model of human liver disease, including methods for establishing them and their advantages in studying cystic fibrosis liver disease, acute liver failure, liver regeneration, non-alcoholic fatty liver disease, liver tumors, and xenotransplantation. We also emphasize the importance of genetic engineering techniques, mainly the CRISPR/Cas9 system, which has greatly enhanced the utility of porcine models as a tool for substantially advancing liver disease research. Genetic engineering is expected to propel the pig as one of the irreplaceable animal models for future biomedical research.</div></div>","PeriodicalId":36741,"journal":{"name":"Liver Research","volume":"8 3","pages":"Pages 131-140"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358630","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}