• Autophagy
• Hepatocellular carcinoma
• Microtubule-associated protein tau
• p62

• Humans
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Liver Neoplasms/genetics
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/genetics
• tau Proteins/metabolism
• tau Proteins/genetics
• Lysosomes/metabolism
• Lysosomes/pathology
• Animals
• Mice
• Autophagosomes/metabolism
• Autophagosomes/pathology
• Hep G2 Cells
• Male
• Mice, Nude
• Carcinogenesis/metabolism
• Carcinogenesis/pathology
• Cell Movement
• Female
• Cell Proliferation
• Neoplasm Proteins/metabolism
• Neoplasm Proteins/genetics
• Cell Line, Tumor
• Sorafenib/pharmacology

• 2021jczx-002 Research Fund of Jianghan University
• 81872040 National Natural Science Foundation of China

• MLKL
• acetaminophen
• autophagy
• mitochondria
• noncanonical

• Animals
• Acetaminophen/toxicity
• Chemical and Drug Induced Liver Injury/pathology
• Chemical and Drug Induced Liver Injury/genetics
• Chemical and Drug Induced Liver Injury/etiology
• Chemical and Drug Induced Liver Injury/enzymology
• Protein Kinases/deficiency
• Protein Kinases/genetics
• Mice, Knockout
• Endoplasmic Reticulum Chaperone BiP
• Disease Models, Animal
• Liver/pathology
• Liver/drug effects
• Liver/enzymology
• Mice, Inbred C57BL
• Male
• Mice
• Unfolded Protein Response/drug effects
• Endoplasmic Reticulum Stress/drug effects
• Hepatocytes/drug effects
• Hepatocytes/pathology
• Necrosis
• Analgesics, Non-Narcotic/toxicity

• R01 DK125465 NIDDK NIH HHS
• F31 DK134197 NIDDK NIH HHS
• P30 GM118247 NIGMS NIH HHS
• National Institute of General Medicine
• F31 DK134197 NIH HHS
• R01 DK102142 NIDDK NIH HHS
• P20 GM103549 NIGMS NIH HHS
• National Institute of Diabetes and Digestive and Kidney Diseases
• Liver Disease COBRE
• NIH

• mitophagy
• macroautophagy

• 2021/41/B/ST5/02233 Narodowe Centrum Nauki (National Science Centre)

• Autophagy
• Bilirubin
• Inflammation
• Non-alcoholic fatty liver disease

• Alpha-Asarone
• Autophagy
• Ethanol
• Hepatic Dysfunction
• Oxidative Stress

• Autophagy
• Chronic inflammation
• Gut microbiota
• Insulin resistance
• Intestinal homeostasis
• Metabolic Syndrome

• Autophagy/physiology
• Gastrointestinal Microbiome/physiology
• Metabolic Syndrome/microbiology
• Metabolic Syndrome/metabolism
• Humans
• Insulin Resistance/physiology
• Animals
• Signal Transduction

• Hepatic ischemia/reperfusion injury
• Inflammation
• NF-κB
• Piperine
• TLR4

• Animals
• Mice
• Alkaloids/pharmacology
• Alkaloids/therapeutic use
• Apoptosis/drug effects
• Benzodioxoles/pharmacology
• Benzodioxoles/therapeutic use
• Disease Models, Animal
• Interleukin-1 Receptor-Associated Kinases/metabolism
• Liver/pathology
• Liver/drug effects
• Liver/metabolism
• Liver Diseases/drug therapy
• Liver Diseases/metabolism
• Liver Diseases/pathology
• Mice, Inbred C57BL
• NF-kappa B/metabolism
• Oxidative Stress/drug effects
• Piperidines/pharmacology
• Piperidines/therapeutic use
• Polyunsaturated Alkamides/therapeutic use
• Polyunsaturated Alkamides/pharmacology
• Reperfusion Injury/drug therapy
• Reperfusion Injury/metabolism
• Signal Transduction/drug effects
• Toll-Like Receptor 4/drug effects
• Toll-Like Receptor 4/metabolism

• Hepatoprotection
• Sericin
• Transcriptome profiling

• Humans
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/genetics
• Sericins/pharmacology
• TNF Receptor-Associated Factor 6
• Liver Neoplasms/drug therapy
• Liver Neoplasms/genetics
• Gene Expression Profiling
• Apolipoproteins B

• CU_FRB65_hea(50)_059_33_03 Science Research and Innovation Fund, Chulalongkorn University
• The Second Century Fund (C2F) Chulalongkorn University, Thailand
• The National Research Council of Thailand and Mahidol research grant, Mahidol university, Thailand.

• apoptosis
• cancer
• cell death
• ferroptosis
• liver disease
• liver surgery
• pyroptosis

• R01 DK113592 NIDDK NIH HHS
• 1402/1 Deutsche Forschungsgemeinschaft

• AMPK
• FOXO3a
• Linagliptin
• NFκB
• diethylnitrosamine
• liver damage

• Animals
• Rats
• Dipeptidyl-Peptidase IV Inhibitors
• Linagliptin/pharmacology
• AMP-Activated Protein Kinases
• Diethylnitrosamine/toxicity
• Carcinoma, Hepatocellular/chemically induced
• Carcinoma, Hepatocellular/drug therapy
• Liver Neoplasms/chemically induced
• Liver Neoplasms/drug therapy
• Hypoglycemic Agents
• Protease Inhibitors
• Antiviral Agents
• Anti-Inflammatory Agents

• GRANT5,682 Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia

• Autophagy
• hepatocyte
• high-fat diet
• lipophagy
• non-alcoholic fatty liver disease
• non-parenchymal cells

• Humans
• Autophagy/genetics
• Non-alcoholic Fatty Liver Disease/genetics
• Tumor Suppressor Protein p53
• Diet, High-Fat/adverse effects
• Endothelial Cells
• Mechanistic Target of Rapamycin Complex 1
• Transcription Factors
• GTP Phosphohydrolases
• Sterols
• Jumonji Domain-Containing Histone Demethylases
• Membrane Proteins

• experimental models of disease
• mechanisms of disease

• Animals
• Mice
• Autophagy
• Chemical and Drug Induced Liver Injury/pathology
• Galactosamine/metabolism
• Lipopolysaccharides/pharmacology
• Liver/metabolism
• Liver Failure, Acute/metabolism
• NF-kappa B/metabolism

• 91954116 National Natural Science Foundation of China (National Science Foundation of China)
• no

• Humans
• Sequestosome-1 Protein/metabolism
• Signal Transduction
• Liver Neoplasms/pathology
• NF-kappa B/metabolism
• Liver Diseases, Alcoholic
• Autophagy/physiology

• R01 AG072895 NIA NIH HHS
• R01 DK102142 NIDDK NIH HHS
• R37 AA020518 NIAAA NIH HHS

• autophagy
• fatty liver hemorrhagic syndrome
• laying hens
• mitochondrial
• taurine

• 31772694 National Natural Science Foundation of China
• 31972639 National Natural Science Foundation of China
• 32272695 National Natural Science Foundation of China
• 31672510 National Natural Science Foundation of China
• RC220278 The Scientific Research Funding Projects from the Science and Technology Department of Shenyang

• Adipose-derived stem cells(ADSCs)
• Autophagy
• Histopathology
• Ischemia-reperfusion injury
• Liver

• ER stress
• Gremlin-1
• MAFLD
• autophagy
• mTOR

• Antiviral
• Autophagy
• Hepatitis B virus
• Lithospermic acid
• Polyphenols
• Traditional Chinese medicine

• Mice
• Animals
• Hepatitis B virus
• Hepatitis B Surface Antigens/genetics
• Salvia miltiorrhiza
• Hepatitis B Core Antigens/genetics
• Polyphenols/metabolism
• Herpesvirus 1, Cercopithecine/genetics
• Herpesvirus 1, Cercopithecine/metabolism
• Hepatitis B e Antigens
• DNA, Viral/genetics
• Proto-Oncogene Proteins c-akt/metabolism
• Phosphatidylinositol 3-Kinases/metabolism
• Virus Replication/physiology
• Mice, Inbred C57BL
• Hepatitis B
• Autophagy
• TOR Serine-Threonine Kinases/metabolism
• Mammals/genetics
• Mammals/metabolism

• autophagy
• liver diseases
• natural products
• pharmacodynamics
• scoring system

• Humans
• Biological Products/pharmacology
• Biological Products/therapeutic use
• Autophagy
• Liver Diseases/drug therapy
• Liver
• Drug Discovery

• AKT
• alliin
• autophagy
• molecular docking
• network pharmacology

Background: Calcium oxalate kidney stone is one of the common diseases in the urinary system and has a high recurrence rate. Currently, the pathogenesis of kidney stone and the methods to prevent recurrence are still being investigated. Autophagy, as an event of cellular self-repair, has received attention in the field of kidney stone in recent years. In some current studies, autophagy has shown destructiveness and protectiveness in the pathogenesis of kidney stone. The inhibition or promotion of autophagy may be a key target for future kidney stone therapy. This systematic literature review discusses the function of autophagy in kidney stone pathogenesis in the context of current research and synthesizes the evidence analysis to provide a basis for new future therapies.

Method: We systematically reviewed the literature during September 2021 according to the Preferred Reporting Items for Systematic Evaluation and Meta-Analysis (PRISMA) guidelines. Articles on studying the role of autophagy in the pathogenesis of calcium oxalate kidney stone were extracted from PubMed, MEDLINE, Embase and Scopus, including in vivo versus in vitro experiments. The study topic, language and publication date were not restricted. Two authors (Li and Zhou) searched and screened the literature.

Results: We screened 18 articles from the 33 collected articles, of which 6 conducted in vitro cellular studies, four conducted animal studies, eight conducted cellular studies with animal studies, and five studied human specimens. In early studies, the literature generally concluded that autophagy is deleterious in the development of kidney stone. In 2020, the idea of the protectiveness of autophagy associated with kidney stone was first proposed and focused on targeting transcription factor EB. In addition, the interaction of autophagy with other cellular events and the regulation of signaling molecules are focused on in this paper.

Conclusion: This systematic review provides advances in research on the role of autophagy in renal calculi. The current studies suggest that both upregulation and downregulation of autophagy may ameliorate injury in kidney stone models. The authors prefer the upregulation of autophagy as a future research direction for kidney stone treatment.

Hepatic ischemia-reperfusion injury (IRI) is an adverse consequence of hepatectomy or liver transplantation. Recently, immune mechanisms involved in hepatic IRI have attracted increased attention of investigators working in this area. In specific, group 2 innate lymphoid cells (ILC2s), have been strongly implicated in mediating type 2 inflammation. However, their immune mechanisms as involved with hepatic IRI remain unclear. Here, we reported that the population of ILC2s is increased with the development of hepatic IRI as shown in a mouse model in initial stage. Moreover, M2 type CD45+CD11b+F4/80high macrophages increased and reached maximal levels at 24 h followed by a significant elevation in IL-4 levels. We injected exogenous IL-33 into the tail vein of mice as a mean to stimulate ILC2s production. This stimulation of ILC2s resulted in a protective effect upon hepatic IRI along with an increase in M2 type CD45+CD11b+F4/80high macrophages. In contrast, depletion of ILC2s as achieved with use of an anti-CD90.2 antibody substantially abolished this protective effect of exogenous IL-33 and M2 type CD45+CD11b+F4/80high macrophage polarization in hepatic IRI. Therefore, this exogenous IL-33 induced potentiation of ILC2s appears to regulate the polarization of CD45+CD11b+F4/80high macrophages to alleviate IRI. Such findings provide the foundation for the development of new targets and strategies in the treatment of hepatic IRI.

• Animals
• Immunity, Innate
• Interleukin-33/pharmacology
• Liver/blood supply
• Liver/immunology
• Liver Diseases/immunology
• Lymphocytes
• Macrophages/immunology
• Mice
• Mice, Inbred C57BL
• Reperfusion Injury/immunology

• autophagy
• lipophagy
• mitophagy
• reticulophagy
• non-alcoholic fatty liver disease

• Autophagy
• Hepatocytes
• Humans
• Lipid Droplets/metabolism
• Lipid Metabolism
• Lipids
• Liver/metabolism
• Non-alcoholic Fatty Liver Disease/metabolism

Autophagy, a cellular self-digestion process, involves the degradation of targeted cell components such as damaged organelles, unfolded proteins, and intracellular pathogens by lysosomes. It is a major quality control system of the cell and plays an important role in cell differentiation, survival, development, and homeostasis. Alterations in the cell autophagic machinery have been implicated in several disease conditions, including neurodegeneration, autoimmunity, cancer, infection, inflammatory diseases, and aging. In non-alcoholic fatty liver disease, including its inflammatory form, non-alcoholic steatohepatitis (NASH), a decrease in cell autophagic activity, has been implicated in the initial development and progression of steatosis to NASH and hepatocellular carcinoma (HCC). We present an overview of autophagy as it occurs in mammalian cells with an insight into the emerging understanding of the role of autophagy in NASH and NASH-related HCC.

Background: Though ASPP2 plays an important role in regulating cell apoptosis and autophagy in case of liver injury, there remains a lack of clarity on the molecular mechanism of ASPP2 regulating autophagy and apoptosis.

Methods: A hepatocyte injury model was constructed using HL7702 cell line and TNF-α. The cells were treated by ASPP2 overexpression adenovirus or short hairpin RNA lentivirus and endoplasmic reticulum stress (ERS) or the mammalian target of rapamycin (mTOR) inhibitor or agonist, respectively. The autophagy was detected by means of western blot and Green fluorescent protein-labeled- Microtubule-associated protein light chain 3 (GFP-LC3) plasmid transfection, while the apoptosis was detected through western blot, flow cytometry and TUNEL assay. Besides, the proteins related to ERS and mTOR were detected by western blot.

Results: The low level of ASPP2 expression was accompanied by high-level autophagy and low-level apoptosis and vice versa in case of hepatocyte injury induce by TNF-α. By upregulating the proteins related to mTORC1 and ERS, ASPP2 induced apoptosis but inhibited autophagy. However, the effect of ASPP2 on autophagy and apoptosis can be reversed by the use of mTORC1 and ERS interfering agent, which indicates that ASPP2 regulated autophagy and apoptosis through mTORC1and ERS pathway. ERS treatment made no difference to the expression of ASPP2 and mTOR-related proteins, which suggests the possibility that the regulation of ERS on apoptosis and autophagy could occur in the downstream of ASPP2 and mTOR.

Conclusion: ASPP2 could inhibit autophagy and induce apoptosis through mTORC1-ERS pathway in case of the hepatocyte injury induce by TNF-α. The role of ASPP2-mTORC1-ERS axis was verified in hepatocyte injury, which suggests the possibility that ASPP2 is an important regulatory molecule for the survival and death of hepatocyte.

• ASPP2
• ERS
• apoptosis
• autophagy
• hepatocyte injury
• mTORC1

• autophagy
• circular RNA
• cyanidin-3-glucoside
• hepatocellular carcinoma
• micro RNA

• (TURSP-2020/202) Taif University

Hepatocellular carcinoma (HCC) is a major health problem with the second highest mortality among all cancers and a continuous increase worldwide. HCC is highly resistant to available chemotherapeutic agents, leaving patients with no effective therapeutic option and a poor prognosis. Although an increasing number of studies have elucidated the potential role of autophagy underlying HCC, the complete regulation is far from understood. The different forms of autophagy constitute important cell survival mechanisms that could prevent hepatocarcinogenesis by limiting hepatocyte death and the associated hepatitis and fibrosis at early stages of chronic liver diseases. On the other hand, at late stages of hepatocarcinogenesis, they could support the malignant transformation of (pre)neoplastic cells by facilitating their survival.

Hepatocarcinogenesis is a long process with a complex pathophysiology. The current therapeutic options for HCC management, during the advanced stage, provide short-term survival ranging from 10–14 months. Autophagy acts as a double-edged sword during this process. Recently, two main autophagic pathways have emerged to play critical roles during hepatic oncogenesis, macroautophagy and chaperone-mediated autophagy. Mounting evidence suggests that upregulation of macroautophagy plays a crucial role during the early stages of carcinogenesis as a tumor suppressor mechanism; however, it has been also implicated in later stages promoting survival of cancer cells. Nonetheless, chaperone-mediated autophagy has been elucidated as a tumor-promoting mechanism contributing to cancer cell survival. Moreover, the autophagy pathway seems to have a complex role during the metastatic stage, while induction of autophagy has been implicated as a potential mechanism of chemoresistance of HCC cells. The present review provides an update on the role of autophagy pathways in the development of HCC and data on how the modulation of the autophagic pathway could contribute to the most effective management of HCC.

• chaperone-mediated autophagy
• chemoresistance
• hepatocellular carcinoma
• macroautophagy

• Alcohol Drinking/adverse effects
• Animals
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/deficiency
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism
• Carcinogenesis/metabolism
• Carcinogenesis/pathology
• Carcinoma, Hepatocellular/pathology
• Cell Proliferation
• Diet, Western
• Diethylnitrosamine
• Ethanol/adverse effects
• Gene Deletion
• Inflammation/pathology
• Liver/pathology
• Liver/ultrastructure
• Liver Cirrhosis/complications
• Liver Neoplasms/pathology
• Liver Neoplasms, Experimental/metabolism
• Liver Neoplasms, Experimental/pathology
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Models, Biological
• Tumor Burden
• Mice

• R01 NS078072 NINDS NIH HHS
• P30 CA168524 NCI NIH HHS
• R37 AA020518 NIAAA NIH HHS
• R01 AG072895 NIA NIH HHS
• U01 AA024733 NIAAA NIH HHS
• R01 DK102142 NIDDK NIH HHS

The “rejuvenating” effect of growth differentiation factor 11 (GDF11) is called into question recently, and its role, as well as plausible signaling mechanisms in liver senescence, is unclear. To overexpress or knockdown GDF11, aged male mice are injected with a single dose of adeno‐associated viruses‐GDF11 or adenovirus‐small hairpin RNA‐GDF11, respectively. GDF11 overexpression significantly accelerates liver senescence in aged mice, whereas GDF11 knockdown has opposite effects. Concomitantly, autophagic flux is impaired in livers from GDF11 overexpression mice. Conversely, GDF11 knockdown increases autophagic flux. Moreover, rapamycin successfully restores the impaired autophagic flux and alleviates liver senescence in GDF11 overexpression mice, while the GDF11 knockdown‐mediated benefits are abolished by the autophagy inhibitor bafilomycin A1. GDF11 leads to a drop in lysosomal biogenesis resulting in defective autophagic flux at autophagosome clearance step. Mechanistically, GDF11 significantly activates mammalian target of rapamycin complex 1 (mTORC1) and subsequently represses transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy. Inhibition of mTORC1 or TFEB overexpression rescues the GDF11‐impaired autophagic flux and cellular senescence. Hepatocyte‐specific deletion of GDF11 does not alter serum GDF11 levels and liver senescence. Collectively, suppression of autophagic activity via mTORC1/TFEB signaling may be a critical molecular mechanism by which GDF11 exacerbates liver senescence. Rather than a “rejuvenating” agent, GDF11 may have a detrimental effect on liver senescence.

• autophagy
• hepatocyte
• liver
• senescence

Thyroid hormones control lipid metabolism by exhibiting specific effects on the liver and adipose tissue in a coordinated manner. Different diseases of the thyroid gland can result in hypothyroidism. Hypothyroidism is frequently associated with dyslipidemia. Hypothyroidism-associated dyslipidemia subsequently results in intrahepatic accumulation of fat, leading to nonalcoholic fatty liver disease (NAFLD), which leads to the development of hepatic insulin resistance. The prevalence of NAFLD in the western world is increasing, and evidence of its association with hypothyroidism is accumulating. Since hypothyroidism has been identified as a modifiable risk factor of NAFLD and recent data provides evidence that selective thyroid hormone receptor β (THR-β) agonists are effective in the treatment of dyslipidemia and NAFLD, interest in potential therapeutic options for NAFLD targeting these receptors is growing. In this review, we summarize current knowledge regarding clinical and molecular data exploring the association of hypothyroidism, dyslipidemia and NAFLD.

• NAFLD
• hypothyroidism
• insulin resistance

• alcoholic liver disease
• fish oil
• gut permeability
• inflammation
• lipid metabolism
• microbiota composition
• oxidative stress

The canonical WNT/β-catenin pathway is upregulated in cancers and plays a major role in proliferation, invasion, apoptosis and angiogenesis. Recent studies have shown that cancer processes are involved under normoxic conditions. These findings completely change the way of approaching the study of the cancer process. In this review, we focus on the fact that, under normoxic conditions, the overstimulation of the WNT/β-catenin pathway leads to modifications in the tumor micro-environment and the activation of the Warburg effect, i.e., aerobic glycolysis, autophagy and glutaminolysis, which in turn participate in tumor growth.

The canonical WNT/β-catenin pathway is upregulated in cancers and plays a major role in proliferation, invasion, apoptosis and angiogenesis. Nuclear β-catenin accumulation is associated with cancer. Hypoxic mechanisms lead to the activation of the hypoxia-inducible factor (HIF)-1α, promoting glycolytic and energetic metabolism and angiogenesis. However, HIF-1α is degraded by the HIF prolyl hydroxylase under normoxia, conditions under which the WNT/β-catenin pathway can activate HIF-1α. This review is therefore focused on the interaction between the upregulated WNT/β-catenin pathway and the metabolic processes underlying cancer mechanisms under normoxic conditions. The WNT pathway stimulates the PI3K/Akt pathway, the STAT3 pathway and the transduction of WNT/β-catenin target genes (such as c-Myc) to activate HIF-1α activity in a hypoxia-independent manner. In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. The activation of the Wnt/β-catenin pathway induces gene transactivation via WNT target genes, c-Myc and cyclin D1, or via HIF-1α. This in turn encodes aerobic glycolysis enzymes, including glucose transporter, hexokinase 2, pyruvate kinase M2, pyruvate dehydrogenase kinase 1 and lactate dehydrogenase-A, leading to lactate production. The increase in lactate production is associated with modifications to the tumor microenvironment and tumor growth under normoxic conditions. Moreover, increased lactate production is associated with overexpression of VEGF, a key inducer of angiogenesis. Thus, under normoxic conditions, overstimulation of the WNT/β-catenin pathway leads to modifications of the tumor microenvironment and activation of the Warburg effect, autophagy and glutaminolysis, which in turn participate in tumor growth.

• HIF-1α
• VEGF
• WNT/β-catenin pathway
• Warburg effect
• aerobic glycolysis
• angiogenesis
• autophagy
• cancer
• glutaminolysis
• lactate
• metabolic reprogramming
• normoxia

• Autophagy
• COX6A1
• PLK1
• gefitinib
• hepatotoxicity

• Animals
• Apoptosis
• Autophagy
• Carcinoma, Non-Small-Cell Lung/metabolism
• Cell Cycle Proteins
• Chemical and Drug Induced Liver Injury
• Electron Transport Complex IV/metabolism
• Electron Transport Complex IV/pharmacology
• Gefitinib/pharmacology
• Lung Neoplasms/metabolism
• Mice
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins
• Polo-Like Kinase 1

• Sidt2
• autophagosomes
• cargo proteins
• fusion
• lysosomes

• Autophagosomes
• Autophagy
• Cells, Cultured
• Gene Knockout Techniques
• Hepatocytes
• Humans
• Lysosomal Membrane Proteins/genetics
• Lysosomes
• Nucleotide Transport Proteins

Artemisinin and its derivatives belong to a family of drugs approved for the treatment of malaria with known clinical safety and efficacy. In addition to its anti-malarial effect, artemisinin displays anti-viral, anti-inflammatory, and anti-cancer effects in vivo and in vitro. Recently, much attention has been paid to the therapeutic role of artemisinin in liver diseases. Several studies suggest that artemisinin and its derivatives can protect the liver through different mechanisms, such as those pertaining to inflammation, proliferation, invasion, metastasis, and induction of apoptosis and autophagy. In this review, we provide a comprehensive discussion of the underlying molecular mechanisms and signaling pathways of artemisinin and its derivatives in treating liver diseases. Further pharmacological research will aid in determining whether artemisinin and its derivatives may serve as promising medicines for the treatment of liver diseases in the future.

• Anti-inflammatory
• Apoptosis
• Artemisinin
• Liver disease
• Malaria

Liver fibrosis is a potentially reversible pathophysiological event, leading to excess deposition of extracellular matrix (ECM) components and taking place as the net result of liver fibrogenesis, a dynamic and highly integrated process occurring during chronic liver injury of any etiology. Liver fibrogenesis and fibrosis, together with chronic inflammatory response, are primarily involved in the progression of chronic liver diseases (CLD). As is well known, a major role in fibrogenesis and fibrosis is played by activated myofibroblasts (MFs), as well as by macrophages and other hepatic cell populations involved in CLD progression. In the present review, we will focus the attention on the emerging pathogenic role of hypoxia, hypoxia-inducible factors (HIFs) and related mediators in the fibrogenic progression of CLD.

• chronic liver diseases
• hypoxia
• hypoxia-inducible factors
• liver fibrogenesis
• liver fibrosis

Hepatic ischemia-reperfusion (IR) injury is one of the severe complications associated with liver surgery and leads to liver dysfunction. PPARγ is always linked with various physiologic pathways, and it can alleviate liver damage in IR injury.

In this study, we explored the potential mechanism of PPARγ in the pathogenesis of hepatic IR injury by mice model.

After treated with si-PPARγ or rosiglitazone, mice were subjected to hepatic ischemia-reperfusion. Liver tissue and blood samples were collected to evaluate liver injury and detected relative mRNA and protein expressions.

The expression of PPARγ was increased after reperfusion. And the alleviation of PPARγ aggravated the liver damage in IR; at the same time, upregulation of the expression of PPARγ released the liver damage. And these effects of PPARγ in IR were related to the AMPK/mTOR/autophagy signaling pathway.

PPARγ plays an important role in hepatic IR injury at least partly via the AMPK/mTOR/autophagy pathway.

• AALD
• DILI
• HCC
• Lipophagy
• Mitophagy
• NAFLD

• Nrf2
• alcohol-induced liver injury
• autophagy
• green tea extract
• lipid accumulation
• oxidative stress

• Anemoside B4
• Autophagy
• Liver injury
• Sepsis
• mTOR

• carcinogenic mechanisms
• hepatitis B virus
• hepatocellular carcinoma
• therapy

• metabolic disorders
• immunopathogenesis

• Animals
• Autophagy/drug effects
• Chemical and Drug Induced Liver Injury/therapy
• Glycyrrhetinic Acid/adverse effects
• Glycyrrhetinic Acid/analogs & derivatives
• Male
• Mice
• Rats
• Rats, Sprague-Dawley
• Tripeptidyl-Peptidase 1

Ischemia-reperfusion injury (IRI) is a complex pathophysiological process that is often characterized as a blood circulation disorder caused due to various factors (such as traumatic shock, surgery, organ transplantation, burn, and thrombus). Severe metabolic dysregulation and tissue structure destruction are observed upon restoration of blood flow to the ischemic tissue. Theoretically, IRI can occur in various tissues and organs, including the kidney, liver, myocardium, and brain, among others. The advances made in research regarding restoring tissue perfusion in ischemic areas have been inadequate with regard to decreasing the mortality and infarct size associated with IRI. Hence, the clinical treatment of patients with severe IRI remains a thorny issue. Peroxisome proliferator-activated receptor γ (PPARγ) is a member of a superfamily of nuclear transcription factors activated by agonists and is a promising therapeutic target for ameliorating IRI. Therefore, this review focuses on the role of PPARγ in IRI. The protective effects of PPARγ, such as attenuating oxidative stress, inhibiting inflammatory responses, and antagonizing apoptosis, are described, envisaging certain therapeutic perspectives.