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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。
Pub Date : 2023-06-01 DOI: 10.3390/livers3020014
Anup Ramachandran, Hartmut Jaeschke
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.
线粒体是维持细胞能量稳态的关键细胞器。因此,它们的功能障碍会对负责能量密集型代谢功能的细胞(如肝细胞)造成严重后果。在过去的几十年里,广泛的研究已经确定线粒体功能受损是过量对乙酰氨基酚(APAP)引起的肝损伤病理生理学的核心特征,这是美国最常见的急性肝衰竭原因。虽然肝细胞线粒体氧化和亚硝化应激与诱导线粒体通透性转变在APAP过量后得到了很好的认识,但最近的研究揭示了细胞器在APAP病理生理中的作用的更多细节。这篇简明的综述强调了这些新的进展,这些进展确立了线粒体在APAP病理生理中的核心作用,并将它们置于文献中早期信息的背景下。我们将讨论线粒体形态的适应性改变、细胞铁在线粒体功能障碍中的作用以及细胞器在apap诱导损伤后肝脏恢复中的重要性。
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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
Pub Date : 2023-05-29 DOI: 10.3390/livers3020020
R. Weiskirchen, S. Friedman
Hepatic stellate cells (HSCs) are a liver-specific mesenchymal cell type located in the Dissé space between hepatocytes and sinusoidal endothelial cells [...]
肝星状细胞(HSCs)是一种肝脏特异性间充质细胞类型,位于肝细胞和窦内皮细胞之间的间隙。
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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
Pub Date : 2023-05-25 DOI: 10.3390/livers3020019
J. Sommer, W. Thasler, A. Bosserhoff, C. Hellerbrand
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.
肝星状细胞(HSCs)的活化是肝纤维化的关键事件。此外,活化的造血干细胞也在肝细胞癌(HCC)的进展中发挥重要作用。骨形态发生蛋白14 (Bone morphogenetic protein 14, BMP14)是TGF-β/BMP超家族成员。到目前为止,大多数研究都是在骨和软骨形成和体内平衡的背景下分析BMP14。本研究的目的是评估BMP14在肝纤维化和HCC中的表达和功能。BMP14的表达在原代人造血干细胞的体外激活过程中增加,在肝纤维化小鼠模型中也增加。在人类HCC以及非肿瘤肝组织中,BMP14的表达与α-平滑肌肌动蛋白(α-SMA)之间存在显著相关性,α-平滑肌肌动蛋白是一种已知的HSC激活标志物。在活化的造血干细胞中,rnai介导的BMP14抑制导致转录因子分化抑制因子1 (ID1)和ID2的表达减少,这是BMP信号传导的已知靶点。有趣的是,在BMP14缺失的细胞中,α-SMA和胶原蛋白的表达也降低,而重组BMP14处理诱导ID1、ID2、α-SMA和胶原蛋白的表达。在人肝癌细胞系中,用重组BMP14处理可诱导增殖、迁移活性和集落形成。总之,我们的数据表明,活化的hsc是纤维化性肝病和HCC中BMP14表达增强的主要细胞来源,并表明BMP14具有促纤维化和促肿瘤作用。未来的分析将揭示这种可溶性生长因子作为慢性肝病患者纤维化和HCC进展的治疗靶点或预后标志物的潜力。
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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
Pub Date : 2023-05-17 DOI: 10.3390/livers3020018
Tehreem Zorob, Muhammad-Awais Farooqi, A. Ahsan, Abdullah Zaki, M. Rathore, H. Farooqi
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.
每年约有1.185亿人献血,以挽救宝贵的生命。捐献的血液也可能与血源性感染有关。巴基斯坦人口约2.47亿,是病毒性肝炎的流行国家,在健康献血者中出现无症状献血者的风险很高。病毒性肝炎在一般人群中流行率为2.5%,献血及其筛查已成为巴基斯坦卫生当局的严重健康问题。根据世界卫生组织的建议,无症状病毒性肝炎需要筛查以排除潜在患病个体。了解健康献血者中输血传播传染病的流行情况,有助于评估任何人群的疾病负担,提高治疗率,并防止受影响人群出现可怕的并发症。本研究的目的是确定访问巴基斯坦拉瓦尔品第武装部队输血研究所(AFIT)的献血者中显著性tti的患病率和趋势。在这项横断面描述性研究中,共有15405名献血者接受了HBV、HCV、HIV、疟疾和梅毒筛查。大多数献血者是o型阳性血型;ab阴性献血者仅占0.7%。在研究人群中,我们报告了1.06%的HBV, 0.54%的HCV, 0.19%的HIV和0.31%的梅毒阳性无症状献血者。然而,没有发现献血者疟疾呈阳性。据报道,旁遮普省是性传播感染负担最重的省份,18-27岁的年轻人主要持积极态度,这表明有必要开展关于性传播感染的全国性宣传活动。利益攸关方需要加强采血指南,考虑到提供非传染性血液制品的目标,应通过内部和外部审计严格监测采血效果。
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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
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
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.
过量食用富含糖和脂肪的饮食与脂肪组织和肝脏的代谢表现有关。佛手柑由于其抗氧化和抗炎特性,已被用于治疗代谢紊乱。这项工作旨在验证佛手柑叶提取物(BLE)对肥胖大鼠脂肪组织-肝轴串扰的影响。在20周的时间里,Wistar大鼠被分为两组:对照组(control)和高糖-脂肪(HSF)饮食组。然后,将动物重新分为三组,为期10周:对照饮食+载体(对照,n=08)、HSF+载体(HSF,n=08,和HSF+BLE(HSF+ABL,n=08。BLE每天通过灌胃(50mg/kg)进行。HSF组表现为肥胖、高血糖、高甘油三酯血症、胰岛素抵抗、肝微泡脂肪变性、肝脏和脂肪组织中较高的炎症和氧化应激。与HSF组相比,HSF+BLE动物通过降低肝和脂肪组织中的甘油三酯水平、胰岛素抵抗、炎症和氧化应激表现出保护作用。与HSF组相比,BLE对肥胖大鼠脂肪组织-肝轴的炎症和氧化应激起作用,这可能反映了胰岛素抵抗和血脂异常的改善。
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引用次数: 0
Peritoneal Immunity in Liver Disease 肝脏疾病的腹膜免疫
Pub Date : 2023-04-26 DOI: 10.3390/livers3020016
Joseph Delo, D. Forton, E. Triantafyllou, A. Singanayagam
The peritoneum represents a confined microenvironment that has an emerging role as a distinct immunological compartment. In health, this niche is mainly populated by a heterogenous group of macrophages and T lymphocytes but also Natural Killer cells and B lymphocytes. Together they are crucial for immunological surveillance, clearance of infection and resolution of inflammation. Development of ascites is a defining feature of decompensated liver cirrhosis, and spontaneous bacterial peritonitis is the most frequent bacterial infection occurring in this patient group. Recent studies of ascitic fluid have revealed quantitative, phenotypic and functional differences in both innate and adaptive immune cells compared to the healthy state. This review summarises current knowledge of these alterations and explores how the peritoneum in chronic liver disease is simultaneously an immunologically compromised site and yet capable of provoking an intense inflammatory response. A better understanding of this might enable identification of new therapeutic targets aimed to rebalance the peritoneal immunity and reduce the reliance on antimicrobials in an era of increasing antimicrobial resistance.
腹膜代表了一个封闭的微环境,它作为一个独特的免疫区室发挥着新的作用。在健康方面,这个生态位主要由巨噬细胞和T淋巴细胞组成的异质性群体占据,也有自然杀伤细胞和B淋巴细胞。它们共同对免疫监测、清除感染和解决炎症至关重要。腹水的发展是失代偿性肝硬化的一个明确特征,自发性细菌性腹膜炎是该患者群体中最常见的细菌感染。最近对腹水的研究揭示了与健康状态相比,先天免疫细胞和适应性免疫细胞在数量、表型和功能上的差异。这篇综述总结了目前对这些变化的认识,并探讨了慢性肝病的腹膜如何同时是一个免疫受损的部位,同时又能够引发强烈的炎症反应。更好地了解这一点可能有助于确定新的治疗靶点,以在抗微生物耐药性不断增加的时代重新平衡腹膜免疫并减少对抗微生物药物的依赖。
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引用次数: 0
Chronicles of HBV and the Road to HBV Cure HBV编年史和HBV治愈之路
Pub Date : 2023-04-20 DOI: 10.3390/livers3020015
Rukaiya Bashir Hamidu, Richard R. Hann, H. Hann
Chronic hepatitis B remains a major public health concern and a leading cause of morbidity and mortality worldwide, specifically through its causative role in chronic liver disease and hepatocellular carcinoma. Worldwide, it affects up to 292 million people. In this paper, we review the historic discovery of the hepatitis B virus and chronicle the significant advances in our understanding of the virus and its interactions with the human host to cause disease. We also overview advancements in therapies for hepatitis B virus and the current absence of curative therapies and highlight on-going therapeutic efforts in search of curative therapies to control transmission and eradicate hepatitis B virus.
慢性乙型肝炎仍然是一个主要的公共卫生问题,也是全球发病率和死亡率的主要原因,特别是其在慢性肝病和肝细胞癌中的致病作用。在全球范围内,它影响了多达2.92亿人。在这篇论文中,我们回顾了乙型肝炎病毒的历史性发现,并记录了我们对该病毒及其与人类宿主相互作用导致疾病的理解方面的重大进展。我们还概述了乙型肝炎病毒治疗的进展和目前缺乏治疗方法,并强调了正在进行的治疗努力,以寻找控制传播和根除乙型肝炎病毒的治疗方法。
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引用次数: 0
Principles of Nutritional Management in Patients with Liver Dysfunction—A Narrative Review 肝功能障碍患者营养管理原则综述
Pub Date : 2023-04-04 DOI: 10.3390/livers3020013
E. M. Elsebaie, Alyaa Nasr Abdel-Fattah, Nagwa Awad Bakr, Kadry Mohamed Attalah, Abdel-Hady Ahmed Aweas
According to studies, the liver’s ability to perform its physiological functions in the body determines the diet of patients with liver diseases. Malnutrition results from the liver’s inability to metabolize nutrients as a result of chronic liver dysfunctions. Objectives: Reviewing the data about diets and dietary supplements that manage liver dysfunctions nutritionally. Results: Malnutrition is particularly prevalent in cirrhosis patients, according to clinical studies. Because malnutrition has a significant negative impact on morbidity, mortality, and quality of life, it is crucial to evaluate all cirrhosis patients, regardless of etiology or severity. A term of supplemental enteral nutrition may be suggested for patients who do not achieve their nutritional objectives. A detailed nutritional and exercise assessment will enable the development of an individualized treatment plan that includes dietary and exercise plans. The dietary treatment should outline daily calorie targets with a focus on high-quality protein and address any vitamin and micronutrient deficiencies, with a diet high in those nutrients or supplements. Conclusions: While there is evidence to support the use of particular restricted dietary plans and dietary supplements to manage liver diseases, these findings should be regarded as preliminary until they are confirmed in larger randomized controlled clinical trials.
根据研究,肝脏在体内发挥生理功能的能力决定了肝病患者的饮食。营养不良是由于慢性肝功能紊乱导致肝脏无法代谢营养物质。目的:回顾饮食和膳食补充剂对肝功能紊乱的营养管理数据。结果:根据临床研究,营养不良在肝硬化患者中尤其普遍。由于营养不良对发病率、死亡率和生活质量有显著的负面影响,因此评估所有肝硬化患者至关重要,无论病因或严重程度如何。对于没有达到营养目标的患者,可以建议使用补充肠内营养。详细的营养和运动评估将有助于制定包括饮食和运动计划在内的个性化治疗计划。饮食治疗应概述每日卡路里目标,重点关注高质量蛋白质,并解决任何维生素和微量营养素缺乏问题,饮食中应富含这些营养素或补充剂。结论:虽然有证据支持使用特定的限制性饮食计划和膳食补充剂来治疗肝病,但在大型随机对照临床试验中得到证实之前,这些发现应被视为初步发现。
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引用次数: 0
An Updated Review on Advances in Hydrogel-Based Nanoparticles for Liver Cancer Treatment 水凝胶纳米颗粒用于肝癌治疗的最新进展综述
Pub Date : 2023-03-27 DOI: 10.3390/livers3020012
Bahareh Farasati Far, Ali Attaripour Isfahani, Elnaz Nasiriyan, Ali Pourmolaei, Golnaz Mahmoudvand, A. Karimi Rouzbahani, Mohammed Namiq Amin, M. Naimi-Jamal
More than 90% of all liver malignancies are hepatocellular carcinomas (HCCs), for which chemotherapy and immunotherapy are the ideal therapeutic choices. Hepatocellular carcinoma is descended from other liver diseases, such as viral hepatitis, alcoholism, and metabolic syndrome. Normal cells and tissues may suffer damage from common forms of chemotherapy. In contrast to systemic chemotherapy, localized chemotherapy can reduce side effects by delivering a steady stream of chemotherapeutic drugs directly to the tumor site. This highlights the significance of controlled-release biodegradable hydrogels as drug delivery methods for chemotherapeutics. This review discusses using hydrogels as drug delivery systems for HCC and covers thermosensitive, pH-sensitive, photosensitive, dual-sensitive, and glutathione-responsive hydrogels. Compared to conventional systemic chemotherapy, hydrogel-based drug delivery methods are more effective in treating cancer.
超过90%的肝脏恶性肿瘤是肝细胞癌(hcc),化疗和免疫治疗是理想的治疗选择。肝细胞癌起源于其他肝脏疾病,如病毒性肝炎、酒精中毒和代谢综合征。正常的细胞和组织可能会受到普通形式的化疗的损害。与全身化疗相比,局部化疗可以通过将稳定的化疗药物流直接输送到肿瘤部位来减少副作用。这凸显了可生物降解的控释水凝胶作为化疗药物递送方法的重要性。本综述讨论了将水凝胶作为HCC的药物传递系统,包括热敏、ph敏、光敏、双敏和谷胱甘肽反应性水凝胶。与传统的全身化疗相比,基于水凝胶的给药方法在治疗癌症方面更有效。
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引用次数: 4
Unresectable Hepatocellular Carcinoma: A Review of New Advances with Focus on Targeted Therapy and Immunotherapy 不可切除肝细胞癌:以靶向治疗和免疫治疗为重点的新进展综述
Pub Date : 2023-03-13 DOI: 10.3390/livers3010011
Bahareh Farasati Far, Dorsa Rabie, P. Hemati, Parastoo Fooladpanjeh, Neda Faal Hamedanchi, Nima Broomand Lomer, A. Karimi Rouzbahani, M. Naimi-Jamal
With an expected incidence of more than 1 million cases by 2025, liver cancer remains a problem for world health. With over 90% of cases, hepatocellular carcinoma (HCC) is the most prevalent kind of liver cancer. In this review, we presented the range of experimental therapeutics for patients with advanced HCC, the successes and failures of new treatments, areas for future development, the evaluation of dose-limiting toxicity in different drugs, and the safety profile in patients with liver dysfunction related to the underlying chronic liver disease. In addition to the unmet demand for biomarkers to guide treatment decisions and the burgeoning fields of immunotherapy and systemic therapy in hepatocellular carcinoma, the development of old and new drugs, including their failures and current advancements, has been reviewed. This review aims to evaluate the updated optimal clinical treatment of unresectable hepatocellular carcinomas in clinical practice, mainly through targeted therapy. Although surgical treatment can significantly enhance the survival probability of early and intermediate-stage patients, it is unsuitable for most HCC patients due to a lack of donors. Due to their severe toxicity, the few first-line anti-HCC drugs, such as sorafenib, are often reserved for advanced HCC patients for whom other therapies have failed. The second-line drugs are usually alternatives for patients with intolerance or resistance. Consequently, the ongoing growth of possible preclinical drugs and studies on miRNAs, lncRNAs, and numerous other signaling pathway targets for developing novel drugs may introduce additional treatment prospects for HCC.
预计到2025年,癌症的发病率将超过100万例,这仍然是世界健康的一个问题。肝细胞癌(HCC)是癌症中最常见的一种,占90%以上。在这篇综述中,我们介绍了晚期HCC患者的实验治疗方法的范围、新治疗方法的成功与失败、未来发展的领域、不同药物的剂量限制毒性评估,以及与潜在慢性肝病相关的肝功能障碍患者的安全性。除了对指导治疗决策的生物标志物的需求未得到满足,以及肝细胞癌免疫疗法和系统治疗领域的蓬勃发展外,还对新旧药物的开发,包括它们的失败和当前的进展进行了综述。这篇综述旨在评估临床实践中不可切除肝细胞癌的最新最佳临床治疗方法,主要通过靶向治疗。尽管手术治疗可以显著提高早期和中期患者的生存概率,但由于缺乏供体,它不适合大多数HCC患者。由于其严重的毒性,为数不多的一线抗HCC药物,如索拉非尼,通常保留给其他治疗失败的晚期HCC患者。二线药物通常是不耐受或耐药患者的替代品。因此,可能的临床前药物的不断增长以及对miRNA、lncRNA和许多其他用于开发新药的信号通路靶点的研究可能会为HCC带来额外的治疗前景。
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引用次数: 1
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Livers
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