An inducible sphingosine kinase 1 in hepatic stellate cells potentiates liver fibrosis.

Hepatic stellate cells (HSCs) play a role in hepatic fibrosis and sphingosine kinase (SphK) is involved in biological processes. As studies on the regulatory mechanisms and functions of SphK in HSCs during liver fibrosis are currently limited, this study aimed to elucidate the regulatory mechanism and connected pathways of SphK upon HSC activation. The expression of SphK1 was higher in HSCs than in hepatocytes, and upregulated in activated primary HSCs.

Parkin-Mediated Mitophagy by TGF-β Is Connected with Hepatic Stellate Cell Activation.

Hepatic stellate cells (HSCs) are the main contributors to the development and progression of liver fibrosis. Parkin is an E3 ligase involved in mitophagy mediated by lysosomes that maintains mitochondrial homeostasis. Unfortunately, there is little information regarding the regulation of parkin by transforming growth factor-β (TGF-β) and its association with HSC trans-differentiation.

Extract Alleviates Acute Liver Injury by Antagonizing Inflammasome-Mediated Pyroptosis.

(CS), a subtropical species, was reported to have antioxidant and antibacterial effects. However, the anti-inflammatory effects of CS have not been studied. This study aimed to investigate whether the 70% ethanol extract of the CS leaf (CSL3) inhibited lipopolysaccharide (LPS)-induced inflammatory responses and LPS and ATP-induced pyroptosis in macrophages.

Identification of Histone Lysine Acetoacetylation as a Dynamic Post-Translational Modification Regulated by HBO1.

Ketone bodies have long been known as a group of lipid-derived alternative energy sources during glucose shortages. Nevertheless, the molecular mechanisms underlying their non-metabolic functions remain largely elusive. This study identified acetoacetate as the precursor for lysine acetoacetylation (Kacac), a previously uncharacterized and evolutionarily conserved histone post-translational modification.

Protective Effect of Extract against UVB-Induced Photodamage in Keratinocytes.

Ultraviolet B (UVB) rays disrupt the skin by causing photodamage via processes such as reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, DNA damage, and/or collagen degradation. is an evergreen tree native to the southern Korean peninsula. Although it is known to have antioxidant and anti-inflammatory effects, its protective effect against photodamage in keratinocytes has not been investigated.

REDD1 attenuates hepatic stellate cell activation and liver fibrosis via inhibiting of TGF-β/Smad signaling pathway.

Liver fibrosis is caused by repetitive hepatic injury. Regulated in development and DNA damage response 1 (REDD1) gene is induced by various stresses and has been studied in cell proliferation and survival. However, the role of REDD1 in hepatic stellate cell activation and hepatic fibrogenesis has not yet been investigated.

Protective Effect of Extract against High-Fat Diet Induced Nonalcoholic Fatty Liver Disease through Nrf-2/HO-1 Pathway.

Nonalcoholic fatty liver disease is the most common chronic disease affecting a wide range of the world's population and associated with obesity-induced metabolic syndrome. It is possibly emerging as a leading cause of life-threatening liver diseases for which a drug with a specific therapeutic target has not been developed yet. Previously, there have been reports on the benefits of (CT) for treating obesity and diabetes via regulation of metabolic processes, such as lipogenesis, lipolysis, and inflammation.

Transforming Growth Factor Beta-Induced Foxo3a Acts as a Profibrotic Mediator in Hepatic Stellate Cells.

Hepatic stellate cells (HSCs) are major contributors to hepatic fibrogenesis facilitating liver fibrosis. Forkhead box O 3a (FoxO3a) is a member of the forkhead transcription factor family, which mediates cell proliferation and differentiation. However, the expression and function of FoxO3a during HSC activation remain largely unknown.

Emerging roles of ferroptosis in liver pathophysiology.

Ferroptosis is a widely recognized process of regulated cell death linking redox state, metabolism, and human health. It is considered a defense mechanism against extensive lipid peroxidation, a complex process that may disrupt the membrane integrity, eventually leading to toxic cellular injury. Ferroptosis is controlled by iron, reactive oxygen species, and polyunsaturated fatty acids.

5-Caffeoylquinic acid ameliorates oxidative stress-mediated cell death via Nrf2 activation in hepatocytes.

Context: 5-Caffeoylquinic acid (5-CQA) is one of the most abundant compounds found in natural foods including coffee.

Objective: We investigated whether 5-CQA had a cytoprotective effect through the NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) signalling pathway.

Materials And Methods: Nrf2 activation in response to 5-CQA treatment at the concentration of 10-100 μM is evaluated by Western blotting of Nrf2 and ARE reporter gene assay as well as its target gene expression in HepG2 cells.

Hepatoprotective Effect of Neoagarooligosaccharide via Activation of Nrf2 and Enhanced Antioxidant Efficacy.

Neoagarooligosaccharides (NAOS) are generated by β-agarases, which cleave the β-1,4 linkage in agarose. Previously, we reported that NAOS inhibited fat accumulation in the liver and decreased serum cholesterol levels. However, the hepatoprotective effect of NAOS on acute liver injury has not yet been investigated.

Induction of E6AP by microRNA-302c dysregulation inhibits TGF-β-dependent fibrogenesis in hepatic stellate cells.

Hepatic stellate cells (HSCs) are essential for liver fibrosis. E6 associated protein (E6AP) is one of the E3-ubiquitin-protein ligase and has been studied in proliferation and cellular stress. Currently, no information is available on the role of E6AP on transforming growth factor-β (TGF-β) signaling and hepatic fibrogenesis.

Extract and Its Major Constituents Inhibit Oxidative Stress-Induced Liver Injury.

The fruits, leaves, and roots of have been reported to contain large amounts of vitamin B, vitamin C, and flavonoids. They exhibit various physiological activities such as antitumor and anti-inflammatory effects. However, the hepatoprotective effects of extracts against oxidative stress-mediated liver injury have not yet been investigated.

Inhibitory Effect of Sestrin 2 on Hepatic Stellate Cell Activation and Liver Fibrosis.

Hepatic fibrosis results from chronic liver injury and inflammatory responses. Sestrin 2 (Sesn2), an evolutionarily conserved antioxidant enzyme, reduces the severities of acute hepatitis and metabolic liver diseases. However, the role of Sesn2 in the pathogenesis of liver fibrosis remains obscure.

Bamboo Stems ( variety henosis) Containing Polyphenol Mixtures Activate Nrf2 and Attenuate Phenylhydrazine-Induced Oxidative Stress and Liver Injury.

This study was designed to investigate the hepatoprotective effect of bamboo stems using in vitro and in vivo experimental liver damage models. Ethyl acetate fraction of 80% ethanol extract of stem (PN3) containing polyphenols had a higher reporter gene activity as monitored by the activity of the NF-E2-related factor (Nrf2) antioxidant pathway in cells in comparison to extracts from other species and under other conditions. The Nrf2 was translocated from the cytosol to the nucleus in response to PN3, followed by induction of the Nrf2 target gene expression, including , , and in HepG2 cells.

Induction of REDD1 via AP-1 prevents oxidative stress-mediated injury in hepatocytes.

Regulated in development and DNA damage responses 1 (REDD1) is an inducible gene in response to various stresses, which functions as a negative regulator of the mammalian target of rapamycin protein kinase in complex 1. In the present study, we identified the role of REDD1 under the oxidative stress-mediated hepatocyte injury and its regulatory mechanism. REDD1 protein was increased in HO or tert-butylhydroperoxide (t-BHP)-treated hepatocytes HO also elevated REDD1 mRNA levels.

Gα overexpression induced by miR-16 dysregulation contributes to liver fibrosis by promoting autophagy in hepatic stellate cells.

Background & Aims: Hepatic stellate cells (HSCs) have a role in liver fibrosis. Guanine nucleotide-binding α-subunit 12 (Gα) converges signals from G-protein-coupled receptors whose ligand levels are elevated in the environment during liver fibrosis; however, information is lacking on the effect of Gα on HSC trans-differentiation. This study investigated the expression of Gα in HSCs and the molecular basis of the effects of its expression on liver fibrosis.

Potent Anti-Inflammatory and Antiadipogenic Properties of Bamboo (Sasa coreana Nakai) Leaves Extract and Its Major Constituent Flavonoids.

The pro-inflammatory response and recruitment of macrophages into adipose tissue contribute to metabolic dysfunction. Here, we reported the anti-inflammatory and antiadipogenic effects of the methanol (MeOH) extract and ethyl acetate (EtOAc) fraction of bamboo leaf and its molecular mechanism in RAW264.7 cells and 3T3-L1 adipocytes, respectively.

Activating transcription factor 6-dependent sestrin 2 induction ameliorates ER stress-mediated liver injury.

Endoplasmic reticulum (ER) stress is characterized by an accumulation of misfolded proteins, and ER stress reduction is essential for maintaining tissue homeostasis. However, the molecular mechanisms that protect cells from ER stress are not completely understood. The present study investigated the role of sestrin 2 (SESN2) on ER stress and sought to elucidate the mechanism responsible for the hepatoprotective effect of SESN2 in vitro and in vivo.

Sestrin2 protects against acetaminophen-induced liver injury.

Acetaminophen (APAP) overdose accounts for half of the cases of acute liver failure worldwide. We previously reported that Sestrin2 (Sesn2) protects against d-galactosamine/lipopolysaccharide-induced acute fulminant liver failure. In this study, we demonstrated that Sesn2 protects APAP-induced liver injury in mice, using a recombinant adenovirus encoding Sesn2 (Ad-Sesn2).

The Role of Lipin-1 in the Regulation of Fibrogenesis and TGF-β Signaling in Hepatic Stellate Cells.

The adipogenic transcriptional regulation was reported to inhibit transdifferentiation of hepatic stellate cells (HSCs), which constitute the main fibrogenic cell type in the liver. Lipin-1 exhibits a dual function: an enzyme that catalyzes the conversion of phosphatidate to diacylglycerol and a transcriptional regulator. However, the involvement of Lipin-1 in the regulation of transforming growth factor-β (TGF-β) signaling and fibrogenesis in HSCs is not fully understood.