In practice, commonly used criteria comprise platelet count of 50 000/µL or more, prothrombin time of 50% or more and serum bilirubin of 3 mg/dL or less. For tumors more than 3 cm in diameter, TACE is frequently performed first, followed by additional RFA.8 According to the report of the 18th follow-up survey, 1-, 3- and 5-year survival rates for RFA were 95.0%, 76.7%

and 56.3%, respectively.9 Radiofrequency ablation is usually performed percutaneously; however, this method can be adapted by performing RFA laparoscopically for lesions on the liver surface or touching neighboring organs such as the intestines or diaphragm,23 and can also be carried out with artificial pleural effusion for lesions under Ixazomib chemical structure the diaphragm or when the lungs intrude on the puncture route.24,25 Artificial ascites can also be used to prevent perforation of the

digestive tract for lesions touching the intestines,24–28 and an endoscopic nasobiliary drainage tube can be used to cool the bile duct before treatment when the lesion is close to the bile duct and the latter is at risk of damage.24,29 For lesions in which the tumor boundaries are not clearly demarcated and that are difficult to visualize under b-mode USG, or when performing additional treatment to secure ablative margins around the target lesion, treatment can be assisted using contrast USG using Sonazoid24,30,31 or a real-time virtual sonography system that synchronizes image data from or multidetector-row computed PtdIns(3,4)P2 tomography with the position of the USG probe, and Angiogenesis inhibitor simultaneously

displays the USG images and virtual images from CT data.32 TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION is widely used in Japan to treat HCC.9 Usually, an adequate amount of emulsion containing oil-based contrast agent Lipiodol and anticancer agents is injected through a catheter then the selected arteries are embolized by embolic agents. Formerly, the embolic agents used in Japan were the absorbent gelatin sponge materials Gelfoam or Spongel treated to create fine fragments, but Gelpart porous gelatin granules were approved for health insurance coverage in 2006 and are now in common use. Superselective TACE is generally used in Japan to minimize damage to non-tumorous areas by using a microcatheter to embolize only the cancerous subsegment.33–35 Epirubicin and cisplatin are commonly used as anticancer agents, and miriplatin, a new platinum drug, came into use in 2010.36,37 Indications for TACE are wide-ranging, and the procedure is generally performed in patients with hypervascular HCC who are not indicated for surgery or local therapy for reasons such as multiple bilobar HCC, liver dysfunction, old age or comorbidity, and in whom the first branch from the main portal vein is not occluded.

The total blood loss, red blood cell transfusion requirement and progression to severe PPH were significantly reduced in the women who received TA compared to the control group [44]. A further, large multinational randomized trial is currently enrolling [World Maternal Antifibrinolytic (WOMAN) Trial] to investigate the impact of TA administration (1 g IV) on the selleck kinase inhibitor rate of hysterectomy and mortality in women with PPH [45]. A major concern among clinicians

still exists about the prolonged use of TA in women during pregnancy because of the possible increased risk of thromboembolism. Indeed, TA inhibits fibrinolysis and carries a potential risk of thrombosis especially in high risk patients. Therefore prolonged use of TA is not recommended in pregnancy and its use is contraindicated in women with previous history of thromboembolism. Other adverse effects of TA are minor and include nausea or diarrhoea and sometimes, orthostatic reactions. More importantly, no mutagenic activities of TA and no foetal abnormalities were identified in early studies in animals: also excretion in breast milk is low and

therefore TA can be used safely in lactating women [39]. 1-deamino-8-D-arginine vasopressin is a synthetic analogue of vasopressin. DDAVP increases VWF and FVIII plasma concentrations without important side effects when administered to healthy volunteers or patients with mild haemophilia A (HA) and VWD. DDAVP has been widely used for the treatment of these diseases for over 30 years [46]. DDAVP is Caspase inhibitor review most effective in patients with mild forms of type 1 VWD, especially those who have normal VWF in storage sites. It is ineffective in type 3 VWD and contraindicated in type 2B VWD,

because of the transient appearance of thrombocytopenia [47]. DDAVP has also been proven to be effective in patients with mild-moderate HA: their clinical response seems to correlate with age, baseline FVIII levels and genotype [48]. A systematic review on the use of DDAVP during pregnancy, delivery and postpartum was recently performed by Trigg et al. [49]. DDAVP was used successfully during the first and second trimester in 51 pregnancies for prevention of bleeding prior to invasive PND procedures with no reported neonatal complications. Maternal side effects associated with DDAVP were generally mild and included facial flushing DOCK10 and headache. The most common indication for use of DDAVP was the prevention of PPH in women with IBD. Of the 172 pregnancies that received DDAVP prophylaxis, no significant bleeding complications were reported in 167 deliveries, without any premature births or neonatal complications [49]. Concerns about DDAVP use in pregnancy are mainly due to the very few cases complicated by seizure secondary to the water intoxication observed in the postpartum period. Safe use can be achieved by avoiding water overload and appropriate dosing of DDAVP with no more than 1–2 injections per day.

The major portion of liver mass is reconstituted within 72-84 hours, and the entire process is complete within 7-10 days. Several patterns of immediate-early, delayed-early, and liver-specific genes have been defined during the 10-day period post-PH. The orchestration may be mediated by a negative feedback between up-regulated miRNAs and target mRNAs involved in miRNA maturation and function, such as Dicer, Drosha, Pasha, Ago2, PACT, and TRBP, allowing cell proliferation, and restoration of the liver mass. Overall, this study has documented genomewide miRNA changes during liver regeneration after 70% PH. We also described a negative

selleck chemicals llc feedback loop between miRNAs and their processing genes,

which appears to be an efficient mechanism for the homeostatic regulation of miRNAs. The early up-regulation of miRNAs might contribute to the priming period of LR, whereas the later normalization of these miRNAs might allow the later accurate cell growth and restoration of liver size. In conclusion, the synchronous model of cell replication of ∼95% of hepatocytes after 70% liver resection provides a novel model, with dynamic flux of the miRNAs affecting their biogenesis, and provides a much-needed resource for studying both mechanisms controlling their synthesis, but also their degradation and loss, of which little is known. Additional Supporting Information may be Temozolomide found in the online version of this article. “
“Aim:  Little is known about the appropriate use of peginterferon-α-2b (PEG IFN-α-2b) or ribavirin (RBV) in genotype 1 chronic hepatitis C (CH-C) patients with complete early virological response (cEVR). Female patients, especially the older,

2-hydroxyphytanoyl-CoA lyase are known to experience inferior treatment outcomes. Method:  A total of 150 CH-C patients with cEVR treated for 48 weeks (n = 104) or 52–64 weeks (n = 46) with PEG IFN-α-2b and RBV combination therapy were retrospectively analyzed to evaluate the benefits of extended treatment. Results:  In the 48-week group, patients without a sustained virological response (SVR) were more often female (P = 0.004) and had received a significantly lower total RBV dose (P = 0.003) than those with SVR. The SVR rate in these female patients was similar to males with hepatitis C virus (HCV) RNA negativity at treatment week 8 (P = 0.413); however, it was lower than that in males with HCV RNA negativity at treatment week 12 (P = 0.005). In the 52–64-week group, although the total RBV dose (mg/kg) after treatment week 48 was less in females than in males (P = 0.027), the SVR rate in females was equivalent to that in males (P = 0.604). Conclusion:  Genotype 1 CH-C patients treated with PEG IFN-α-2b and RBV combination therapy without SVR were more often female and had received a lower total RBV dose than males.

7-9 Their ex vivo monocyte responses to LPS are significantly

enhanced relative to controls and this LPS hyperresponsiveness can be reproduced in vitro by exposure of the human macrophage cell line MonoMac6 to ethanol for 6 days.10 The enhanced and sustained inflammatory response seen in AAH is, however, in complete contradistinction to the normal processing of portal endotoxin by the liver.11 The liver is normally subject to tonic endotoxin exposure by way of the portal vein and it is effective at clearing this endotoxin from the blood without an inflammatory response. The phenomenon of “endotoxin tolerance” thereby renders endotoxin-exposed Kupffer cells refractory to further LPS stimulation, maintaining an anti- rather than proinflammatory cytokine output.12 Selleckchem Fostamatinib It is therefore somewhat unexpected that the proinflammatory response to endotoxin in AAH should be so disproportionately high, particularly considering that it is the Kupffer cells themselves that are key to maintaining hepatic endotoxin tolerance.13 It has become increasingly clear, therefore, that the enhancement of cytokine gene expression and perpetuation of the inflammatory response

is the key event in the pathogenesis of AAH.14 Despite its clear importance for the pathogenesis of AAH, the mechanism for enhanced inflammatory cytokine release in this disease remains unclear. In this study we address the novel hypothesis that the enhanced inflammatory cytokine response results from the direct actions of ethanol itself on the final common pathway of cytokine gene transcriptional Compound Library manufacturer regulation by histone acetylation. In its untranscribed state DNA is tightly coiled around histone protein octamers and the resulting chromatin is compacted into a closed tertiary structure from which the histone tails protrude, but in which the DNA is inaccessible to polymerases

Akt inhibitor involved in gene transcription. Gene activation by transcription factors involves coactivator proteins with histone acetyl transferase (HAT) activity that acetylate key lysine residues in the histone tails. The negatively charged acetyl groups cause a conformational change in chromatin that allows RNA polymerases access to the DNA, facilitating gene transcription. Termination of transcription is mediated through histone deacetylases (HDAC), which release free acetate and allow the chromatin to resume its closed, untranscribed conformation.15 Various HDACs are able to modulate inflammatory gene transcription, including class I and II HDACs, which can be recruited by transcriptional repressors such as the activated glucocorticoid receptor and class III HDACs, known as sirtuins (SIRT), which are active in the presence of nicotinamide adenine dinucleotide (NAD+).16 Ethanol has been demonstrated to increase total histone acetylation in rat liver17 with increased HAT and reduced HDAC activity18 and separate investigations have established that both SIRT expression and activity can be inhibited by ethanol in the liver.

Beyond the regulation of bile acid synthesis, FXR improves insulin sensitivity and glucose uptake in adipose tissue, and the liver and the skeletal muscle, by regulating metabolic genes such as PEPCK, G6Pase, and FBP1.[86] Moreover, FXR suppresses pro-inflammatory genes like interferon γ, tumor necrosis factor-α, see more and interleukin-6 by affecting NFkappaB transcriptional activity.[86, 87] However, this broad spectrum is likely to result in adverse side effects, and selective FXR agonists are required to mainly alter gene expression relevant to NASH and insulin resistance. In the MCD model of steatohepatitis, WAY-362450,

a synthetic FXR ligand, protected against hepatic inflammation and fibrosis without inhibiting hepatic triglyceride accumulation.[88] this website Currently, obeticholic acid, a semi-synthetic bile acid derivative, is tested in patients with biopsy-proven NASH (ClinicalTrials.gov Identifier: NCT01265498).[86] An unwanted side effect of obeticholic acid is exacerbation of itching. A pro-inflammatory intestinal microbiome has been observed in mice and patients with NASH.[37-39, 41] In a model of genetic dyslipidemia

using ApoE-deficient mice, supplementation of the probiotic VSL#3 that contains different lactobacilli and bifidobacteria improved insulin signaling in hepatocytes and ameliorated adipose tissue inflammation,[89] and the supplementation of lactobacillus casei shirota protected Chloroambucil mice from increased activation of TLR4 and hepatic steatosis induced by a high-fructose diet.[90] In an open-label pilot study in 20 patients with biopsy-proven NASH, supplementation of a probiotic containing lactobacilli and bifidobacteria

over 6 months improved hepatic steatosis, as determined by MRI and serum transaminases.[91] Together with the human randomized controlled study on fecal transplantation of a healthy microbiota in patients with insulin resistance,[42] these recent reports support the role of microbiota in the pathogenesis of insulin resistance and NASH, partly by reducing bacterial inflammatory triggers and nutrient extractions and modification. It also hints to a role of prebiotics, that is nutrients that favor the growth of certain bacterial species, that may likely play in the treatment of obesity and NASH.[92] NAFLD has become a global challenge to our health-care systems. Changes in lifestyle and nutrition have put large parts of the population at risk of developing NASH, cirrhosis, and liver cancer. In contrast to other liver diseases with emerging therapeutic options, and despite the benefit of lifestyle changes, NAFLD will remain a great health problem necessitating (adjunctive) pharmacological therapies. Moreover, given the unpredictable course of this common disease, improved non-invasive biomarkers are urgently needed to better assess NAFLD/NASH activity and fibrosis, and to speed up drug development.

These GSI-IX cost results have important implications for the development of antibody-based therapies against HBV. “
“Background and Aim:  Cancer invasion and metastasis are characterized by epithelial-mesenchymal transition (EMT). Hepatocellular carcinoma

(HCC) causes metastasis and significant mortality. Elucidating factors promoting EMT in HCC are necessary to develop effective therapeutic strategies. Methods:  The LH86 cell line was developed in our laboratory from well-differentiated HCC without associated hepatitis or cirrhosis and used as a model to study EMT in HCC. Effects of transforming growth factor β-1, epidermal growth factor, hepatocyte growth factor and basic fibroblast growth factor (bFGF) were examined using morphology, molecular markers, effects on migration and tumorigenicity. The involvement of cyclooxygenase-2 (COX-2) and Akt were examined. Results:  LH86 cells display epithelial morphology. Transforming-growth-factor-β-1-, epidermal-growth-factor-, hepatocyte-growth-factor- and basic-fibroblast-growth-factor-induced mesenchymal changes in them were

associated with loss of E-cadherin, albumin, α-1 anti-trypsin expression and increased expression of vimentin, collagen I and fibronectin. There was associated increased migration, tumorigenicity and increased expression of COX-2, prostaglandin

E2 (PGE2), Akt and phosphorylated Selleckchem Metformin Akt. Inhibition of COX-2 and Akt pathways led to inhibition of characteristics of EMT. Conclusions:  Multiple growth factors induce EMT in HCC. COX-2 Immune system and Akt may mediate EMT-associated development and progression of HCC and molecular targeting of COX-2 and Akt may be an effective therapeutic or chemopreventive strategy in advanced and metastatic HCC. “
“In the 2008 guidelines for the treatment of patients with cirrhosis, who are infected with hepatitis B virus (HBV), the main goal is to normalize levels of alanine and aspartate aminotransferases by eliminating HBV or reducing viral loads. In patients with compensated cirrhosis, the clearance of HBV from serum is aimed for by entecavir, as the main resort, for histological improvement toward the prevention of hepatocellular carcinoma (HCC). In patients with decompensated cirrhosis, by contrast, meticulous therapeutic strategies are adopted for the reversal to compensation, toward the eventual goal of decreasing the risk of HCC. For maintaining liver function and preventing HCC, branched chain amino acids and nutrient supplements are applied, in addition to conventional liver supportive therapies. For patients with chronic hepatitis B, separate guidelines are applied to those younger than 35 years and those aged 35 years or older.

These Metformin results have important implications for the development of antibody-based therapies against HBV. “
“Background and Aim:  Cancer invasion and metastasis are characterized by epithelial-mesenchymal transition (EMT). Hepatocellular carcinoma

(HCC) causes metastasis and significant mortality. Elucidating factors promoting EMT in HCC are necessary to develop effective therapeutic strategies. Methods:  The LH86 cell line was developed in our laboratory from well-differentiated HCC without associated hepatitis or cirrhosis and used as a model to study EMT in HCC. Effects of transforming growth factor β-1, epidermal growth factor, hepatocyte growth factor and basic fibroblast growth factor (bFGF) were examined using morphology, molecular markers, effects on migration and tumorigenicity. The involvement of cyclooxygenase-2 (COX-2) and Akt were examined. Results:  LH86 cells display epithelial morphology. Transforming-growth-factor-β-1-, epidermal-growth-factor-, hepatocyte-growth-factor- and basic-fibroblast-growth-factor-induced mesenchymal changes in them were

associated with loss of E-cadherin, albumin, α-1 anti-trypsin expression and increased expression of vimentin, collagen I and fibronectin. There was associated increased migration, tumorigenicity and increased expression of COX-2, prostaglandin

E2 (PGE2), Akt and phosphorylated Sirolimus price Akt. Inhibition of COX-2 and Akt pathways led to inhibition of characteristics of EMT. Conclusions:  Multiple growth factors induce EMT in HCC. COX-2 www.selleck.co.jp/products/Gemcitabine(Gemzar).html and Akt may mediate EMT-associated development and progression of HCC and molecular targeting of COX-2 and Akt may be an effective therapeutic or chemopreventive strategy in advanced and metastatic HCC. “
“In the 2008 guidelines for the treatment of patients with cirrhosis, who are infected with hepatitis B virus (HBV), the main goal is to normalize levels of alanine and aspartate aminotransferases by eliminating HBV or reducing viral loads. In patients with compensated cirrhosis, the clearance of HBV from serum is aimed for by entecavir, as the main resort, for histological improvement toward the prevention of hepatocellular carcinoma (HCC). In patients with decompensated cirrhosis, by contrast, meticulous therapeutic strategies are adopted for the reversal to compensation, toward the eventual goal of decreasing the risk of HCC. For maintaining liver function and preventing HCC, branched chain amino acids and nutrient supplements are applied, in addition to conventional liver supportive therapies. For patients with chronic hepatitis B, separate guidelines are applied to those younger than 35 years and those aged 35 years or older.

These Idasanutlin in vitro results have important implications for the development of antibody-based therapies against HBV. “
“Background and Aim:  Cancer invasion and metastasis are characterized by epithelial-mesenchymal transition (EMT). Hepatocellular carcinoma

(HCC) causes metastasis and significant mortality. Elucidating factors promoting EMT in HCC are necessary to develop effective therapeutic strategies. Methods:  The LH86 cell line was developed in our laboratory from well-differentiated HCC without associated hepatitis or cirrhosis and used as a model to study EMT in HCC. Effects of transforming growth factor β-1, epidermal growth factor, hepatocyte growth factor and basic fibroblast growth factor (bFGF) were examined using morphology, molecular markers, effects on migration and tumorigenicity. The involvement of cyclooxygenase-2 (COX-2) and Akt were examined. Results:  LH86 cells display epithelial morphology. Transforming-growth-factor-β-1-, epidermal-growth-factor-, hepatocyte-growth-factor- and basic-fibroblast-growth-factor-induced mesenchymal changes in them were

associated with loss of E-cadherin, albumin, α-1 anti-trypsin expression and increased expression of vimentin, collagen I and fibronectin. There was associated increased migration, tumorigenicity and increased expression of COX-2, prostaglandin

E2 (PGE2), Akt and phosphorylated selleck screening library Akt. Inhibition of COX-2 and Akt pathways led to inhibition of characteristics of EMT. Conclusions:  Multiple growth factors induce EMT in HCC. COX-2 Microbiology inhibitor and Akt may mediate EMT-associated development and progression of HCC and molecular targeting of COX-2 and Akt may be an effective therapeutic or chemopreventive strategy in advanced and metastatic HCC. “
“In the 2008 guidelines for the treatment of patients with cirrhosis, who are infected with hepatitis B virus (HBV), the main goal is to normalize levels of alanine and aspartate aminotransferases by eliminating HBV or reducing viral loads. In patients with compensated cirrhosis, the clearance of HBV from serum is aimed for by entecavir, as the main resort, for histological improvement toward the prevention of hepatocellular carcinoma (HCC). In patients with decompensated cirrhosis, by contrast, meticulous therapeutic strategies are adopted for the reversal to compensation, toward the eventual goal of decreasing the risk of HCC. For maintaining liver function and preventing HCC, branched chain amino acids and nutrient supplements are applied, in addition to conventional liver supportive therapies. For patients with chronic hepatitis B, separate guidelines are applied to those younger than 35 years and those aged 35 years or older.

apoB-100, apolipoprotein B-100; ANOVA, analysis of variance; ASGPR1, asialoglycoprotein receptor; CAD, coronary artery disease; FH, familial hypercholesterolemia; FL-LDL, fluorescently labeled LDL; GWAS, genome-wide association studies; hESC, human embryonic stem cell; hiPSC, human induced pluripotent stem cell; HMG-CoA, 3-hydroxy-3-methyl-glutaryl-coenzyme A; HNF4a, hepatocyte nuclear factor 4a; iPSC, induced pluripotent stem cell; LDL-C, low-density lipoprotein cholesterol; LY294002 mRNA, messenger RNA; qRT-PCR, quantitative reverse-transcription polymerase chain reaction; SREBP, sterol regulatory element binding protein; VLDL, very low-density lipoprotein. A detailed description

of the Materials and Methods is provided in the Supporting Information. Procedures used for the generation of iPSCs and differentiation of pluripotent stem cells to hepatocytes have been described.4, 9 All culture of human embryonic stem cells (hESCs) and generation of iPSCs was approved by the MCW Human Stem Cell

Research Oversight Committee (hSCRO approval #09-005), and all animal procedures were approved by the Medical College of Wisconsin’s Institutional Animal Care and Use Committee. FH is an autosomal dominant dyslipidemia caused by mutations in the LDLR gene that result in severely elevated plasma LDL-C levels and premature cardiovascular disease.10 The liver is central to the pathogenesis of FH, and homozygous FH patients are selleck products successfully treated with liver transplantation. Although

hepatocytes are the key cells that control cholesterol flux, LDLR mutations have primarily been studied using fibroblasts.10 Such studies Orotidine 5′-phosphate decarboxylase revealed that LDLR-deficient fibroblasts had an impaired capacity to internalize LDL, which gave rise to the paradigm that the level of LDL-C in serum is determined by the rate of LDL clearance.11 However, modifications to this model have recently been proposed based on evidence suggesting that FH patients often possess profoundly elevated hepatic very low-density lipoprotein (VLDL) production.12 Given the extensive understanding of FH and the fact that single nucleotide polymorphisms have been identified in the vicinity of the LDLR gene, we felt that hepatocytes derived from FH hiPSCs would offer an ideal model to define the feasibility of using iPSCs to study genetic variations that could affect complex hepatic metabolism. The generation of iPSCs from a patient with early onset atherosclerotic disease with hypercholesterolemia has been described7; however, the genetic lesion was undefined. In addition, this study by Rashid et al. was designed only to test whether cells derived from LDLR-deficient iPSCs could internalize LDL. However, LDLR-mediated uptake of LDL is not a hepatocyte-specific process, and most cells use this pathway to internalize cholesterol.

2 NKT cells are abundant in the liver. They recognize lipid antigens presented by CD1d and had different roles in liver diseases. NKT cells produce a wide range of cytokines promptly after activation.23 It is well accepted that Th1 cytokines suppress fibrosis, whereas Th2 cytokines promote fibrosis.24 In wildtype (WT) mice, it was reported that NKT cells can suppress the activation of HSC.22 But in different animal models and in human patients the conclusions were controversial.25, 26 Although the acceleration of HBV infection to liver fibrosis Selleckchem Barasertib have been extensively observed in clinical settings,

the immune response during this process is not clear, especially in the condition of the HBV carriers with no obvious symptoms. In this study, by using HBV transgenic mice (HBV-tg) that mimic human HBV healthy carriers,27 we found liver fibrosis spontaneously occurred in old age of HBV-tg mice, and, importantly, CAL-101 mw HBV-tg mice were much more sensitive to the hepatotoxin CCl4-induced liver injury and liver fibrosis with the accompanied overactivation of HSCs. Further study demonstrated

that hepatic NKT cells from HBV-tg mice could directly activate HSCs and thereafter induce liver fibrosis in the experiments of cellular depletion and adoptive transfer, and IL-4 and IL-13 secreted by NKT cells were considered a crucial step for the activation of HSCs. α-SMA: α smooth muscle actin; CCl4: carbon tetrachloride; ECM: extracellular matrix; HBV: hepatitis B virus; HBV-tg: HBV transgenic mice; HSC: hepatic stellate cells; IFN-γ, interferon gamma; IL: interleukin; MMP: matrix metalloproteinase; MNC: mononuclear cell; mRNA: messenger RNA; NKT, natural killer T; qPCR: quantitative polymerase chain reaction; TIMP: tissue inhibitor of metalloproteinase. ifenprodil HBV transgenic mice C57BL/6J-TgN (AlblHBV) 44Bri, which contains HBV genome S, pre-S, and X domains, were purchased from VITALRIVER experiment animal company (Beijing, China), who obtained the animals from Jackson Laboratory

(Bar Harbor, ME). C57BL/6 mice were also purchased from VITALRIVER experiment animal company. Rag1−/− mice were purchased from Model Animal Research Center (Nanjing, China), who obtained the mice from Jackson Laboratory. Mice were housed in a specific pathogen-free facility and used according to the regulations of animal care of University of Science and Technology of China. For chronic liver injury and fibrosis, male 7 to 10-week-old C57BL/6 and HBV-tg mice (weighing about 20-25 g) were injected (intraperitoneally, i.p., 2 times a week) with 0.5 μL per gram of body weight of pure CCl4 diluted with olive oil (Sigma). After several weeks’ injections (2, 4, 10, and 14 weeks, respectively), mice were sacrificed 72 hours following the last CCl4 injection, and liver tissues and serum were collected. For acute liver injury, both mice were injected CCl4 once and then killed and analyzed at different timepoints.