scholarly journals Macrophage Polarization and Its Role in Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Cheng Wang ◽  
Cheng Ma ◽  
Lihong Gong ◽  
Yuqin Guo ◽  
Ke Fu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Acute Liver Injury ◽  
Macrophage Polarization ◽  
Pathological Conditions ◽  
Pathogenic Factors ◽  
Hepatic Macrophages ◽  
Stimulation Of

Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity and polarization. Under pathological conditions, in addition to the resident macrophages, other macrophages are also recruited to the diseased tissues, and polarize to various phenotypes (mainly M1 and M2) under the stimulation of various factors in the microenvironment, thus playing different roles and functions. Liver diseases are hepatic pathological changes caused by a variety of pathogenic factors (viruses, alcohol, drugs, etc.), including acute liver injury, viral hepatitis, alcoholic liver disease, metabolic-associated fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Recent studies have shown that macrophage polarization plays an important role in the initiation and development of liver diseases. However, because both macrophage polarization and the pathogenesis of liver diseases are complex, the role and mechanism of macrophage polarization in liver diseases need to be further clarified. Therefore, the origin of hepatic macrophages, and the phenotypes and mechanisms of macrophage polarization are reviewed first in this paper. It is found that macrophage polarization involves several molecular mechanisms, mainly including TLR4/NF-κB, JAK/STATs, TGF-β/Smads, PPARγ, Notch, and miRNA signaling pathways. In addition, this paper also expounds the role and mechanism of macrophage polarization in various liver diseases, which aims to provide references for further research of macrophage polarization in liver diseases, contributing to the therapeutic strategy of ameliorating liver diseases by modulating macrophage polarization.

scholarly journals An Integrative Pharmacology Based Analysis of Refined Liuweiwuling Against Liver Injury: A Novel Component Combination and Hepaprotective Mechanism

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuan Gao ◽  
Wei Shi ◽  
Hongyu Yao ◽  
Yongqiang Ai ◽  
Ruisheng Li ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Cell Apoptosis ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Acute Liver Injury ◽  
Network Pharmacology ◽  
Active Ingredients ◽  
Anti Inflammatory

Liver disease is a major cause of illness and death worldwide. In China, liver diseases, primarily alcoholic and nonalcoholic fatty liver disease, and viral hepatitis, affect approximately 300 million people, resulting in a major impact on the global burden of liver diseases. The use of Liuweiwuling (LWWL), a traditional Chinese medicine formula, approved by the Chinese Food and Drug Administration for decreasing aminotransferase levels induced by different liver diseases. Our previous study indicated a part of the material basis and mechanisms of LWWL in the treatment of hepatic fibrosis. However, knowledge of the materials and molecular mechanisms of LWWL in the treatment of liver diseases remains limited. Using pharmacokinetic and network pharmacology methods, this study demonstrated that the active components of LWWL were involved in the treatment mechanism against liver diseases and exerted anti-apoptosis and anti-inflammatory effects. Furthermore, esculetin, luteolin, schisandrin A and schisandrin B may play an important role by exerting anti-inflammatory and hepatoprotective effects in vitro. Esculeti and luteolin dose-dependently inhibited H2O2-induced cell apoptosis, and luteolin also inhibited the NF-κB signaling pathway in bone marrow-derived macrophages. schisandrin A and B inhibited the release of ROS in acetaminophen (APAP)-induced acute liver injury in vitro. Moreover, LWWL active ingredients protect against APAP-induced acute liver injury in mice. The four active ingredients may inhibit oxidative stress or inflammation to exert hepatoprotective effect. In conclusion, our results showed that the novel component combination of LWWL can protect against APAP-induced acute liver injury by inhibiting cell apoptosis and exerting anti-inflammatory effects.

scholarly journals Protective Effects of Melatonin on Neurogenesis Impairment in Neurological Disorders and Its Relevant Molecular Mechanisms

2020 ◽  
Vol 21 (16) ◽  
pp. 5645
Author(s):  
Joseph Wai-Hin Leung ◽  
Kwok-Kuen Cheung ◽  
Shirley Pui-Ching Ngai ◽  
Hector Wing-Hong Tsang ◽  
Benson Wui-Man Lau
Keyword(s):  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Neurological Diseases ◽  
Protective Effects ◽  
Neurological Outcomes ◽  
Pathological Conditions ◽  
Neurological Illnesses ◽  
Neurological Conditions ◽  
Traditional Understanding

Neurogenesis is the process by which functional new neurons are generated from the neural stem cells (NSCs) or neural progenitor cells (NPCs). Increasing lines of evidence show that neurogenesis impairment is involved in different neurological illnesses, including mood disorders, neurogenerative diseases, and central nervous system (CNS) injuries. Since reversing neurogenesis impairment was found to improve neurological outcomes in the pathological conditions, it is speculated that modulating neurogenesis is a potential therapeutic strategy for neurological diseases. Among different modulators of neurogenesis, melatonin is a particularly interesting one. In traditional understanding, melatonin controls the circadian rhythm and sleep–wake cycle, although it is not directly involved in the proliferation and survival of neurons. In the last decade, it was reported that melatonin plays an important role in the regulation of neurogenesis, and thus it may be a potential treatment for neurogenesis-related disorders. The present review aims to summarize and discuss the recent findings regarding the protective effects of melatonin on the neurogenesis impairment in different neurological conditions. We also address the molecular mechanisms involved in the actions of melatonin in neurogenesis modulation.

scholarly journals Postinfantile Giant Cell Hepatitis with Features of Acute Severe Autoimmune Hepatitis Probably Triggered by Diclofenac in a Patient with Primary Myelofibrosis

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Pinelopi Arvaniti ◽  
Kalliopi Zachou ◽  
George K. Koukoulis ◽  
George N. Dalekos
Keyword(s):  
Liver Disease ◽  
Autoimmune Hepatitis ◽  
Giant Cell ◽  
Liver Diseases ◽  
Acute Liver Injury ◽  
Rescue Therapy ◽  
Primary Myelofibrosis ◽  
Life Saving ◽  
History Of ◽  
Giant Cell Hepatitis

Giant cell hepatitis (GCH) is commonly reported in neonatal and infantile liver diseases but rarely in adults where the term postinfantile GCH (PIGCH) is used. PIGCH is associated with many diseases, including drugs toxicity, viruses, and autoimmune liver diseases, with autoimmune hepatitis (AIH) being the most prevalent. We present a case of PIGCH in a 76-year-old female without known history of liver disease who suffered from an acute severe episode of hepatitis. After careful exclusion of other hepatitis causes by imaging, virological, immunological, and microbiological investigations, a diagnosis of acute severe AIH (AS-AIH) was established. The patient was started on corticosteroids but she did not respond and died 3 days later because of advanced acute liver failure. Postmortem liver biopsy showed typical PIGCH lesions. Physicians must keep this catastrophic entity in mind in cases of unexplained acute liver injury as, contrary to our case, prompt rescue therapy with corticosteroids may be life-saving.

scholarly journals Dietary Melatonin Supplementation Could Be a Promising Preventing/Therapeutic Approach for a Variety of Liver Diseases

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1135 ◽  
Author(s):  
Francesca Bonomini ◽  
Elisa Borsani ◽  
Gaia Favero ◽  
Luigi Rodella ◽  
Rita Rezzani
Keyword(s):  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Antioxidant Properties ◽  
Therapeutic Strategies ◽  
Beneficial Effects ◽  
Pathological Conditions ◽  
Positive Effect ◽  
And Oxidative Stress

In the therapeutic strategies, the role of diet is a well-established factor that can also have an important role in liver diseases. Melatonin, identified in animals, has many antioxidant properties and it was after discovered also in plants, named phytomelatonin. These substances have a positive effect during aging and in pathological conditions too. In particular, it is important to underline that the amount of melatonin produced by pineal gland in human decreases during lifetime and its reduction in blood could be related to pathological conditions in which mitochondria and oxidative stress play a pivotal role. Moreover, it has been indicated that melatonin/phytomelatonin containing foods may provide dietary melatonin, so their ingestion through balanced diets could be sufficient to confer health benefits. In this review, the classification of liver diseases and an overview of the most important aspects of melatonin/phytomelatonin, concerning the differences among their synthesis, their presence in foods and their role in health and diseases, are summarized. The findings suggest that melatonin/phytomelatonin supplementation with diet should be considered important in preventing different disease settings, in particular in liver. Currently, more studies are needed to strengthen the potential beneficial effects of melatonin/phytomelatonin in liver diseases and to better clarify the molecular mechanisms of action.

scholarly journals The Application of Induced Pluripotent Stem Cells Against Liver Diseases: An Update and a Review

2021 ◽  
Vol 8 ◽  
Author(s):  
Lei Zhang ◽  
Ke Pu ◽  
Xiaojun Liu ◽  
Sarah Da Won Bae ◽  
Romario Nguyen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Disease ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Disease Modeling ◽  
Health Concern ◽  
Promising Alternative ◽  
Induced Pluripotent

Liver diseases are a major health concern globally, and are associated with poor survival and prognosis of patients. This creates the need for patients to accept the main alternative treatment of liver transplantation to prevent progression to end-stage liver disease. Investigation of the molecular mechanisms underpinning complex liver diseases and their pathology is an emerging goal of stem cell scope. Human induced pluripotent stem cells (hiPSCs) derived from somatic cells are a promising alternative approach to the treatment of liver disease, and a prospective model for studying complex liver diseases. Here, we review hiPSC technology of cell reprogramming and differentiation, and discuss the potential application of hiPSC-derived liver cells, such as hepatocytes and cholangiocytes, in refractory liver-disease modeling and treatment, and drug screening and toxicity testing. We also consider hiPSC safety in clinical applications, based on genomic and epigenetic alterations, tumorigenicity, and immunogenicity.

scholarly journals Caveolin-1 Deficiency Protects Mice Against Carbon Tetrachloride-Induced Acute Liver Injury Through Regulating Polarization of Hepatic Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Ziheng Yang ◽  
Jie Zhang ◽  
Yan Wang ◽  
Jing Lu ◽  
Quan Sun
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Liver Diseases ◽  
Acute Liver Injury ◽  
Mrna Levels ◽  
Alcoholic Fatty Liver ◽  
Caveolin 1 ◽  
Hepatic Macrophages ◽  
M1 Phenotype

Polarization of hepatic macrophages plays a crucial role in the injury and repair processes of acute and chronic liver diseases. However, the underlying molecular mechanisms remain elusive. Caveolin-1 (Cav1) is the structural protein of caveolae, the invaginations of the plasma membrane. It has distinct functions in regulating hepatitis, cirrhosis, and hepatocarcinogenesis. Given the increasing number of cases of liver cancer, nonalcoholic steatohepatitis, and non-alcoholic fatty liver disease worldwide, investigations on the role of Cav1 in liver diseases are warranted. In this study, we aimed to investigate the role of Cav1 in the pathogenesis of acute liver injury. Wild-type (WT) and Cav1 knockout (KO) mice (Cav1tm1Mls) were injected with carbon tetrachloride (CCl4). Cav1 KO mice showed significantly reduced degeneration, necrosis, and apoptosis of hepatocytes and decreased level of alanine transaminase (ALT) compared to WT mice. Moreover, Cav1 was required for the recruitment of hepatic macrophages. The analysis of the mRNA levels of CD86, tumor necrosis factor (TNF), and interleukin (IL)-6, as well as the protein expression of inducible nitric oxide synthase (iNOS), indicated that Cav1 deficiency inhibited the polarization of hepatic macrophages towards the M1 phenotype in the injured liver. Consistent with in vivo results, the expressions of CD86, TNF, IL-6, and iNOS were significantly downregulated in Cav1 KO macrophages. Also, fluorescence-activated cell sorting (FACS) analysis showed that the proportion of M1 macrophages was significantly decreased in the liver tissues obtained from Cav1 KO mice following CCl4 treatment. In summary, our results showed that Cav1 deficiency protected mice against CCl4-induced acute liver injury by regulating polarization of hepatic macrophages. We provided direct genetic evidence that Cav1 expressed in hepatic macrophages contributed to the pathogenesis of acute liver injury by regulating the polarization of hepatic macrophages towards the M1 phenotype. These findings suggest that Cav1 expressed in macrophages may represent a potential therapeutic target for acute liver injury.

scholarly journals LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma

2020 ◽  
Vol 21 (8) ◽  
pp. 2883
Author(s):  
Young-Ah Kim ◽  
Kwan-Kyu Park ◽  
Sun-Jae Lee
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Hepatic Fibrosis ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Nonalcoholic Fatty Liver ◽  
Underlying Mechanisms

Long non-coding RNAs (lncRNAs) are emerging as important contributors to the biological processes underlying the pathophysiology of various human diseases, including hepatocellular carcinoma (HCC). However, the involvement of these molecules in chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and viral hepatitis, has only recently been considered in scientific research. While extensive studies on the pathogenesis of the development of HCC from hepatic fibrosis have been conducted, their regulatory molecular mechanisms are still only partially understood. The underlying mechanisms related to lncRNAs leading to HCC from chronic liver diseases and cirrhosis have not yet been entirely elucidated. Therefore, elucidating the functional roles of lncRNAs in chronic liver disease and HCC can contribute to a better understanding of the molecular mechanisms, and may help in developing novel diagnostic biomarkers and therapeutic targets for HCC, as well as in preventing the progression of chronic liver disease to HCC. Here, we comprehensively review and briefly summarize some lncRNAs that participate in both hepatic fibrosis and HCC.

scholarly journals Ferroptosis in liver disease: new insights into disease mechanisms

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jing Wu ◽  
Yi Wang ◽  
Rongtao Jiang ◽  
Ran Xue ◽  
Xuehong Yin ◽  
...  
Keyword(s):  
Cell Death ◽  
Liver Disease ◽  
Liver Diseases ◽  
Defense Mechanisms ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Iron Accumulation ◽  
Related Factor ◽  
Drug Induced ◽  
Nonalcoholic Fatty Liver

AbstractCharacterized by excessive iron accumulation and lipid peroxidation, ferroptosis is a novel form of iron-dependent cell death, which is morphologically, genetically, and biochemically distinct from other well-known cell death. In recent years, ferroptosis has been quickly gaining attention in the field of liver diseases, as the liver is predisposed to oxidative injury and generally, excessive iron accumulation is a primary characteristic of most major liver diseases. In the current review, we first delineate three cellular defense mechanisms against ferroptosis (GPx4 in the mitochondria and cytosol, FSP1 on plasma membrane, and DHODH in mitochondria), along with four canonical modulators of ferroptosis (system Xc−, nuclear factor erythroid 2-related factor 2, p53, and GTP cyclohydrolase-1). Next, we review recent progress of ferroptosis studies delineating molecular mechanisms underlying the pathophysiology of several common liver diseases including ischemia/reperfusion-related injury (IRI), nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), hemochromatosis (HH), drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC). Furthermore, we also highlight both challenges and promises that emerged from recent studies that should be addressed and pursued in future investigations before ferroptosis regulation could be adopted as an effective therapeutic target in clinical practice.

scholarly journals Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?

2018 ◽  
Vol 2018 ◽  
pp. 1-25 ◽  
Author(s):  
Luca Parisi ◽  
Elisabetta Gini ◽  
Denisa Baci ◽  
Marco Tremolati ◽  
Matteo Fanuli ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Cancer Type ◽  
Effector Cells ◽  
Chronic Inflammatory Diseases ◽  
Pathological Conditions ◽  
Cellular Components ◽  
Cell Cell

Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1) or alternatively activated (M2). However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in “distant” pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like) and/or builders (M2-like). We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy.

scholarly journals Molecular Functions of Thyroid Hormones and Their Clinical Significance in Liver-Related Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Hsiang Cheng Chi ◽  
Cheng-Yi Chen ◽  
Ming-Ming Tsai ◽  
Chung-Ying Tsai ◽  
Kwang-Huei Lin
Keyword(s):  
Liver Disease ◽  
Thyroid Hormones ◽  
Anticancer Agents ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Hormone Receptors ◽  
Target Genes ◽  
Therapeutic Potential ◽  
Chronic Liver ◽  
Biologically Active

Thyroid hormones (THs) are potent mediators of several physiological processes, including embryonic development, cellular differentiation, metabolism, and cell growth. Triiodothyronine (T3) is the most biologically active TH form. Thyroid hormone receptors (TRs) belong to the nuclear receptor superfamily and mediate the biological functions of T3via transcriptional regulation. TRs generally form heterodimers with the retinoid X receptor (RXR) and regulate target genes upon T3stimulation. Research over the past few decades has revealed that disruption of cellular TH signaling triggers chronic liver diseases, including alcoholic or nonalcoholic fatty liver disease and hepatocellular carcinoma (HCC). Animal model experiments and epidemiologic studies to date imply close associations between high TH levels and prevention of liver disease. Moreover, several investigations spanning four decades have reported the therapeutic potential of T3analogs in lowering lipids, preventing chronic liver disease, and as anticancer agents. Thus, elucidating downstream genes/signaling pathways and molecular mechanisms of TH actions is critical for the treatment of significant public health issues. Here, we have reviewed recent studies focusing on the roles of THs and TRs in several disorders, in particular, liver diseases. We also discuss the potential therapeutic applications of THs and underlying molecular mechanisms.

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