Livers Pub Date : 2024-03-25 DOI: 10.3390/livers4020012

Stephen D. H. Malnick, Ali Abdullah, Fadi Ghanem, Sheral Ohayon Michael, Manuela G. Neuman

引用次数: 0

Functions and Therapeutic Use of Heat Shock Proteins in Hepatocellular Carcinoma 热休克蛋白在肝细胞癌中的功能和治疗用途

Livers Pub Date : 2024-03-04 DOI: 10.3390/livers4010011

Ramakrushna Paul, Smriti Shreya, Shweta Pandey, Srishti Shriya, Aya Abou Hammoud, Christophe F Grosset, Buddhi Prakash Jain

{"title":"Functions and Therapeutic Use of Heat Shock Proteins in Hepatocellular Carcinoma","authors":"Ramakrushna Paul, Smriti Shreya, Shweta Pandey, Srishti Shriya, Aya Abou Hammoud, Christophe F Grosset, Buddhi Prakash Jain","doi":"10.3390/livers4010011","DOIUrl":"https://doi.org/10.3390/livers4010011","url":null,"abstract":"Heat shock proteins are intracellular proteins expressed in prokaryotes and eukaryotes that help protect the cell from stress. They play an important role in regulating cell cycle and cell death, work as molecular chaperons during the folding of newly synthesized proteins, and also in the degradation of misfolded proteins. They are not only produced under stress conditions like acidosis, energy depletion, and oxidative stress but are also continuously synthesized as a result of their housekeeping functions. There are different heat shock protein families based on their molecular weight, like HSP70, HSP90, HSP60, HSP27, HSP40, etc. Heat shock proteins are involved in many cancers, particularly hepatocellular carcinoma, the main primary tumor of the liver in adults. Their deregulations in hepatocellular carcinoma are associated with metastasis, angiogenesis, cell invasion, and cell proliferation and upregulated heat shock proteins can be used as either diagnostic or prognostic markers. Targeting heat shock proteins is a relevant strategy for the treatment of patients with liver cancer. In this review, we provide insights into heat shock proteins and heat shock protein-like proteins (clusterin) in the progression of hepatocellular carcinoma and their use as therapeutic targets.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"25 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140265783","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

Translocation of Adenosine A2B Receptor to Mitochondria Influences Cytochrome P450 2E1 Activity after Acetaminophen Overdose. 对乙酰氨基酚过量后，腺苷 A2B 受体向线粒体的转移会影响细胞色素 P450 2E1 的活性。

Livers Pub Date : 2024-03-01 Epub Date: 2023-12-26 DOI: 10.3390/livers4010002

Giselle Sanchez-Guerrero, David S Umbaugh, Abhay A Ramachandran, Antonio Artigues, Hartmut Jaeschke, Anup Ramachandran

{"title":"Translocation of Adenosine A2B Receptor to Mitochondria Influences Cytochrome P450 2E1 Activity after Acetaminophen Overdose.","authors":"Giselle Sanchez-Guerrero, David S Umbaugh, Abhay A Ramachandran, Antonio Artigues, Hartmut Jaeschke, Anup Ramachandran","doi":"10.3390/livers4010002","DOIUrl":"10.3390/livers4010002","url":null,"abstract":"<p><p>The adenosine A2B receptor (A2BAR) is a member of a family of G-protein coupled receptors (GPCRs), which has a low affinity for adenosine and is now implicated in several pathophysiological conditions. We have demonstrated the beneficial effects of A2BAR activation in enhancing recovery after acute liver injury induced by an acetaminophen (APAP) overdose. While receptor trafficking within the cell is recognized to play a role in GPCR signaling, its role in the mediation of A2BAR effects in the context of APAP-induced liver injury is not well understood. This was investigated here, where C57BL/6J mice were subjected to an APAP overdose (300 mg/kg), and the temporal course of A2BAR intracellular localization was examined. The impact of A2BAR activation or inhibition on trafficking was examined by utilizing the A2BAR agonist BAY 60-6583 or antagonist PSB 603. The modulation of A2BAR trafficking via APAP-induced cell signaling was explored by using 4-methylpyrazole (4MP), an inhibitor of Cyp2E1 and JNK activation. Our results indicate that APAP overdose induced the translocation of A2BAR to mitochondria, which was prevented via 4MP treatment. Furthermore, we demonstrated that A2BAR is localized on the mitochondrial outer membrane and interacts with progesterone receptor membrane component 1 (PGRMC1). While the activation of A2BAR enhanced mitochondrial localization, its inhibition decreased PGRMC1 mitochondria levels and blunted mitochondrial Cyp2E1 activity. Thus, our data reveal a hitherto unrecognized consequence of A2BAR trafficking to mitochondria and its interaction with PGRMC1, which regulates mitochondrial Cyp2E1 activity and modulates APAP-induced liver injury.</p>","PeriodicalId":74083,"journal":{"name":"Livers","volume":"4 1","pages":"15-30"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617768","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

Resmetirom: Finally, the Light at the End of the NASH Tunnel? Resmetirom：NASH隧道尽头的曙光终于出现了吗？

Livers Pub Date : 2024-02-26 DOI: 10.3390/livers4010010

A. Lonardo

引用次数: 0

Minimally Invasive Surgery in Liver Transplantation: From Living Liver Donation to Graft Implantation 肝移植中的微创手术：从活体肝脏捐献到移植物植入

Livers Pub Date : 2024-02-17 DOI: 10.3390/livers4010009

E. Avramidou, Konstantinos Terlemes, Afroditi Lymperopoulou, Georgios Katsanos, Nikolaos Antoniadis, Athanasios Kofinas, S. Vasileiadou, Konstantina-Eleni Karakasi, Georgios Tsoulfas

{"title":"Minimally Invasive Surgery in Liver Transplantation: From Living Liver Donation to Graft Implantation","authors":"E. Avramidou, Konstantinos Terlemes, Afroditi Lymperopoulou, Georgios Katsanos, Nikolaos Antoniadis, Athanasios Kofinas, S. Vasileiadou, Konstantina-Eleni Karakasi, Georgios Tsoulfas","doi":"10.3390/livers4010009","DOIUrl":"https://doi.org/10.3390/livers4010009","url":null,"abstract":"Since the end of the 20th century and the establishment of minimally invasive techniques, they have become the preferred operative method by many surgeons. These techniques were applied to liver surgery for the first time in 1991, while as far as transplantation is concerned their application was limited to the living donor procedure. We performed a review of the literature by searching in Pubmed and Scopus using the following keywords: Liver transplantation, Minimally invasive surgery(MIS) living liver donor surgery. Applications of MIS are recorded in surgeries involving the donor and the recipient. Regarding the recipient surgeries, the reports are limited to 25 patients, including combinations of laparoscopic, robotic and open techniques, while in the living donor surgery, the reports are much more numerous and with larger series of patients. Shorter hospitalization times and less blood loss are recorded, especially in centers with experience in a large number of cases. Regarding the living donor surgery, MIS follows the same principles as a conventional hepatectomy and is already the method of choice in many specialized centers. Regarding the recipient surgery, significant questions arise mainly concerning the safe handling of the liver graft.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"380 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140453532","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

Herbal- and Dietary-Supplement-Induced Liver Injury: A Review of the Recent Literature 草药和膳食补充剂诱发的肝损伤：最新文献综述

Livers Pub Date : 2024-02-13 DOI: 10.3390/livers4010008

Palak A. Patel-Rodrigues, Lindsey B. Cundra, Dalal Alhaqqan, Daniel T. Gildea, S. Woo, James H. Lewis

{"title":"Herbal- and Dietary-Supplement-Induced Liver Injury: A Review of the Recent Literature","authors":"Palak A. Patel-Rodrigues, Lindsey B. Cundra, Dalal Alhaqqan, Daniel T. Gildea, S. Woo, James H. Lewis","doi":"10.3390/livers4010008","DOIUrl":"https://doi.org/10.3390/livers4010008","url":null,"abstract":"Herbal-induced liver injury (HILI) continues to increase in prevalence each year due to the ongoing popularity of herbal supplements and complementary and alternative medicines. A detailed literature review of case reports and clinical studies published from March 2021 to March 2023 was performed. We discuss the epidemiology and diagnosis of HILI as well as the current and proposed laws and regulations. The 2021 ACG guidelines and 2022 AASLD practice guidelines for the diagnosis and management of drug and herbal-induced liver injury are discussed. We describe updates to previously reported etiologies of HILI such as ayurveda, ashwagandha, turmeric, kratom, green tea extract, and garcinia cambogia. Newly described supplements resulting in HILI, such as tinospora cordifolia, horse chestnut, alkaline water, and more, are described. We discuss newly and previously identified hepatoprotective herbal supplements as they have been reported in the study of animal models and human liver cells. This review suggests the need for ongoing research on the causes and mechanisms of HILI to ensure its proper diagnosis, prevention, and treatment in the future. The goal of this review is to provide novice and expert readers with knowledge regarding the possible etiologies of HILI and a general overview.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"36 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139840749","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

Herbal- and Dietary-Supplement-Induced Liver Injury: A Review of the Recent Literature 草药和膳食补充剂诱发的肝损伤：最新文献综述

Livers Pub Date : 2024-02-13 DOI: 10.3390/livers4010008

Palak A. Patel-Rodrigues, Lindsey B. Cundra, Dalal Alhaqqan, Daniel T. Gildea, S. Woo, James H. Lewis

{"title":"Herbal- and Dietary-Supplement-Induced Liver Injury: A Review of the Recent Literature","authors":"Palak A. Patel-Rodrigues, Lindsey B. Cundra, Dalal Alhaqqan, Daniel T. Gildea, S. Woo, James H. Lewis","doi":"10.3390/livers4010008","DOIUrl":"https://doi.org/10.3390/livers4010008","url":null,"abstract":"Herbal-induced liver injury (HILI) continues to increase in prevalence each year due to the ongoing popularity of herbal supplements and complementary and alternative medicines. A detailed literature review of case reports and clinical studies published from March 2021 to March 2023 was performed. We discuss the epidemiology and diagnosis of HILI as well as the current and proposed laws and regulations. The 2021 ACG guidelines and 2022 AASLD practice guidelines for the diagnosis and management of drug and herbal-induced liver injury are discussed. We describe updates to previously reported etiologies of HILI such as ayurveda, ashwagandha, turmeric, kratom, green tea extract, and garcinia cambogia. Newly described supplements resulting in HILI, such as tinospora cordifolia, horse chestnut, alkaline water, and more, are described. We discuss newly and previously identified hepatoprotective herbal supplements as they have been reported in the study of animal models and human liver cells. This review suggests the need for ongoing research on the causes and mechanisms of HILI to ensure its proper diagnosis, prevention, and treatment in the future. The goal of this review is to provide novice and expert readers with knowledge regarding the possible etiologies of HILI and a general overview.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"134 43","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139780761","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

High-Dose Acetaminophen as a Treatment for Cancer 大剂量对乙酰氨基酚治疗癌症

Livers Pub Date : 2024-01-31 DOI: 10.3390/livers4010007

Jeffrey Wu, Bradley Maller, Rujul Kaul, Andrea Galabow, A. Bryan, Alexander Neuwelt

{"title":"High-Dose Acetaminophen as a Treatment for Cancer","authors":"Jeffrey Wu, Bradley Maller, Rujul Kaul, Andrea Galabow, A. Bryan, Alexander Neuwelt","doi":"10.3390/livers4010007","DOIUrl":"https://doi.org/10.3390/livers4010007","url":null,"abstract":"The use of high-dose acetaminophen (AAP) with n-acetylcysteine (NAC) rescue was studied as an anti-cancer treatment in phase I trials with promising signals of anti-tumor efficacy. Correlative analysis suggested that AAP has a free-radical-independent mechanism of anti-tumor activity—in contrast to the well-established mechanism of AAP hepatotoxicity. Subsequent “reverse translational” studies in the pre-clinical setting have identified novel mechanisms of action of high-dose AAP, including modulation of JAK-STAT signaling in both the tumor cell and the tumor immune microenvironment. Importantly, these effects are free-radical-independent and not reversed by concurrent administration of the established AAP rescue agents fomepizole and NAC. By administering high-dose AAP concurrently with fomepizole and NAC, 100-fold higher AAP levels than those of standard dosing can be achieved in mice without detected toxicity and with substantial anti-tumor efficacy against commonly used mouse models of lung and breast cancer that are resistant to standard first-line anti-cancer therapies. With these recent advances, additional clinical trials of high-dose AAP with concurrent NAC and fomepizole-based rescue are warranted.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140478240","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

Glycyrrhizinic Acid and Phosphatidylcholine Combination as a Preventive Therapy for Experimental Murine Non-Alcoholic Steatohepatitis 甘草酸和磷脂酰胆碱复方制剂作为实验性小鼠非酒精性脂肪性肝炎的预防疗法

Livers Pub Date : 2024-01-29 DOI: 10.3390/livers4010006

V. Prikhodko, T. M. Matuzok, Vadim E. Karev, A. V. Karavaeva, O. M. Spasenkova, Nadezhda V. Kirillova, D. Ivkin, S. V. Okovityi

{"title":"Glycyrrhizinic Acid and Phosphatidylcholine Combination as a Preventive Therapy for Experimental Murine Non-Alcoholic Steatohepatitis","authors":"V. Prikhodko, T. M. Matuzok, Vadim E. Karev, A. V. Karavaeva, O. M. Spasenkova, Nadezhda V. Kirillova, D. Ivkin, S. V. Okovityi","doi":"10.3390/livers4010006","DOIUrl":"https://doi.org/10.3390/livers4010006","url":null,"abstract":"Non-alcoholic metabolic-associated steatohepatitis (MASH) is a condition characterized by increasingly high prevalence and incidence, and also represents an important unmet medical need when it comes to effective pharmacotherapy. In this work, we aimed to explore the therapeutic possibilities of the synergistic combined use of glycyrrhizinic acid (GA) and phosphatidylcholine (PC) to prevent experimental MASH. Adult C57Bl/6 mice were used to model dietary/toxic MASH and treated orally by either GA (34.3 mg/kg/d) or a GA + PC combination (34.3 + 158.1 mg/kg/d) for 3 months. Animal locomotion, behaviour, short-term memory, physical performance, neuromuscular joint function, blood biochemistry, and oxidative stress marker levels were evaluated, followed by histological examination of the liver, skeletal muscle and sciatic nerve with tissue ammonia and lipid content determination. Real-time polymerase chain reaction was used to measure the relative expression of several pathogenetic transcript markers. GA and PC showed moderate additive synergism in their anti-inflammatory, antioxidant, hypoammonaemic, hypoglycaemic, and pro-cognitive activities. Differential effects of the agents were seen in regard to anxiety- and depression-like behaviour as well as gene expression. Our results indicate partial pharmacological synergism between GA and PC and validate further research of its potential clinical applications.","PeriodicalId":74083,"journal":{"name":"Livers","volume":"32 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140488632","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

The Hepatokine Leukocyte Cell-Derived Chemotaxin-2 Is Elevated in People with Impaired Glycaemic Regulation and Augmented by Acute Exercise 血糖调节功能受损者体内的肝脏因子白细胞衍生趋化因子-2会升高，急性运动会增强其作用

Livers Pub Date : 2024-01-17 DOI: 10.3390/livers4010005

Buket Engin, S. Willis, Sundus Malaikah, J. Sargeant, D. Stensel, C. Jelleyman, G. Ennequin, G. Aithal, Thomas Yates, James A. King

{"title":"The Hepatokine Leukocyte Cell-Derived Chemotaxin-2 Is Elevated in People with Impaired Glycaemic Regulation and Augmented by Acute Exercise","authors":"Buket Engin, S. Willis, Sundus Malaikah, J. Sargeant, D. Stensel, C. Jelleyman, G. Ennequin, G. Aithal, Thomas Yates, James A. King","doi":"10.3390/livers4010005","DOIUrl":"https://doi.org/10.3390/livers4010005","url":null,"abstract":"The hepatokine leukocyte cell-derived chemotaxin-2 (LECT2) promotes insulin resistance and hepatic fibrogenesis. In rodents, acute exercise suppresses circulating LECT2; however, human data are lacking. This study compared circulating LECT2 across populations and explored whether acute exercise impacts circulating LECT2. In Part A (n = 43), data were pooled from three experimental studies, regarding the following groups: healthy individuals, individuals with impaired glycaemic regulation (IGR), and individuals with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (T2DM-MASLD). Generalised linear models assessed differences in circulating LECT2 among groups. Part B (n = 20) involved exercise (30 min, 65% peak oxygen uptake) and control (resting) trials in the healthy and IGR groups. Circulating LECT2 was measured before and at 0, 1, 2 and 3 h post-exercise. Generalised estimating equations assessed differences in LECT2 responses to the trials among groups. In Part A, circulating LECT2 levels were 28.7% and 37.3% higher in the IGR and T2DM-MASLD groups, vs. healthy individuals (p ≤ 0.038), with BMI identified as the main predictor (p = 0.008). In Part B, average circulating LECT2 levels were 6.3% higher after exercise vs. in the control (p < 0.001), with similar responses between groups (p = 0.829). In the combined cohort, circulating LECT2 levels were elevated 1–3 h after exercise vs. control (p ≤ 0.009). LECT2 is elevated in people with dysglycaemia, with BMI as a leading predictor. Contrary to previous rodent work, acute exercise augments, rather than suppresses, circulating LECT2 in humans.","PeriodicalId":74083,"journal":{"name":"Livers","volume":" 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139616758","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

Livers最新文献