This situation requires

immediate attention, given the public health implication of acute viral Tamoxifen hepatitis in older patients,46 those with CLD as well as patients with obesity- and diabetes-related NAFLD. Furthermore, a more uniform set of guidelines for vaccinating patients with CLD is urgently needed. Additional Supporting Information may be found in the online version of this article. “
“Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature. Kang TW, Yevsa T, Woller N, Hoenicke L, Wuestefeld T, Dauch D, et al 2011;479:547-551 Jean-Charles Nault M.D.* †, Giuliana Amaddeo M.D.* †, Jessica Zucman-Rossi M.D., Ph.D.* †, * Inserm, UMR-674, Génomique fonctionnelle des tumeurs

solides, Institut Universitaire d’Hématologie, Paris, France, † Université Paris Descartes, Labex Immuno-oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris, France Kang TW, Yevsa T, Woller N, Hoenicke L, Wuestefeld T, Dauch D, et al. Senescence surveillance of pre-malignant hepatocytes FK506 cell line limits liver cancer development. Nature. 2011;479:547-551. www.nature.com. (Reprinted with permission.) Upon the aberrant activation of oncogenes, normal cells can enter the cellular senescence program, a state of stable cell-cycle arrest, which represents an important barrier against tumour development in vivo. Senescent cells communicate with their environment by secreting various cytokines and growth factors, and it was reported that this ‘secretory phenotype’ can have pro- as well as anti-tumorigenic effects. Here we show that oncogene-induced senescence occurs in otherwise normal murine hepatocytes in vivo. Pre-malignant senescent hepatocytes secrete chemo- and cytokines

and are subject to immune-mediated clearance (designated as ‘senescence surveillance’), which depends on an intact CD4(+) T-cell-mediated adaptive immune response. Impaired immune surveillance of pre-malignant senescent hepatocytes results in selleck screening library the development of murine hepatocellular carcinomas (HCCs), thus showing that senescence surveillance is important for tumour suppression in vivo. In accordance with these observations, ras-specific Th1 lymphocytes could be detected in mice, in which oncogene-induced senescence had been triggered by hepatic expression of Nras(G12V). We also found that CD4(+) T cells require monocytes/macrophages to execute the clearance of senescent hepatocytes. Our study indicates that senescence surveillance represents an important extrinsic component of the senescence anti-tumour barrier, and illustrates how the cellular senescence program is involved in tumour immune surveillance by mounting specific immune responses against antigens expressed in pre-malignant senescent cells. Oncogene activation can induce senescence in human cells.

SVR is expected at the time of the meeting. Safety: There was no further decompensation during the treatment. Mean MELD score before and during treatment was not different (mean MELD before starting treatment is 11.6 and peak MELD during treatment is 13.6). None of the patients were hospitalized

during the therapy. Six patients developed hemoglobin levels < 10 gm/dl and one patient had Hb < 8 gm /dL. None of the patients required red cell transfusion. The average bilirubin during the treatment course was 2.5 mg/dl (range: 0.4-5.5 mg/dl). Conclusion: Rapamycin mouse The simeprevir and sofosbuvir combination was well tolerated by patients with decompensated cirrhosis. The early virological response is similar to the reported data

in compensated cirrhotic patients. Disclosures: Sanjaya K. Satapathy – Advisory Committees or Review Panels: Gilead Satheesh Nair – Advisory Committees or Review Panels: Jansen; Speaking and Teaching: Gilead The following people have nothing to disclose: Shilpa Lingala, Nader Dbouk Background: There is no data available on the use of sofosbu-vir or simeprevir in hepatitis c patients with severe renal insufficiency or dialysis. Aim: To describe our experience with the use of sofosbuvir based regimen in patients with GFR < 30ml/ min who urgently need hepatitis c treatment. Methods: We collected data on 4 male patients with HCV genotype 1 (50% 1a), mean age 58 years who had severe renal insufficiency defined by GFR < 30ml/min or those who are on dilaysis. Two cirrhotic patients check details with ESRD on dilaysis

were bering evaluated for combined liver kidney transplant who had normal hepatic synthetic function (mean albumin 4.3, INR 1, Bilirubin 0.5) and were disinclined to undergo liver transplantation (LT) were started on sofosbuvir 400mg every other day and simeprevir 150 mg every day. One liver transplant recipient developed fibrosing cholestatic hepatitis (FCH) within 3 months post LT with ascites, bilirubin 27 and severe renal impairment requiring dialysis and was started on compassionate sofosburvir 400mg daily and ribavirin 200mg every other day. Fourth patient see more was a post liver-kidney transplant recipient who developed acute antibody mediated rejection of the kidney requiring intense immunosup-pressive therapy and thus was started on sofosbuvir 400mg every other day and simeprevir 150mg daily. Results: The patient with FCH has attained SVR 24 and is cured of HCV. His hepatic function normalized and his GFR also improved significantly to 55ml/min without the need for further dialysis at the end of treatment. Two patients were undetectable on treatment and one patient had low level viremia of 169 IU at week 4. Conclusion: We present the first case series of 4 HCV genotype 1 patients with severe renal insufficiency (GFR < 30), 3/4 on dialysis who are undergoing treatment with sofosbuvir based regimen.

Key Word(s): 1. Ulcerative Colitis; 2. Azathioprine; 3. Efficacy; 4. Appropriate Dose; Presenting Author: ZHONG YINGQIANG Additional Authors: HUANG HUARONG, WU XINHUAN Corresponding Author: ZHONG YINGQIANG Affiliations: Sun Yat-Sen Memorial Hospital, Sun Yat-sen University Objective: To

MLN0128 ic50 study the effects of mesenchymal stem cells (MSCs), the fusion protein of tumor necrosis factor receptor II-IgG Fc (TNFR II-IgG), mesalazine on the disease active index and tissue damage index of the model of SD rats with colitis induced by TNBS. Methods: MSCs were cultured in low-glucose DMEM containing 10% FBS. Rats colitis model induced by TNBS/ethanol. Eighty-one Sprague-Dawley rats were randomly divided into 6 groups, namely the normal control group (A), colitis group (B), MSCs 1 group (C), MSCs 2 group (D), TNFR II-IgG group (E), mesalazine group (F). Scores of disease active index (DAI) was recorded the manifestations of rats, colon macroscopic damage index (CMDI) was described macroscopic features of the colon, and the score of tissue damage index (TDI) were estimated the features of colon under microscipy. Results: Pure MSCs were gained by 3 times of passages. Compared with group A, DAI, CMDI, TDI scores in group B were always significantaly increased (p < 0.05). On day 6 these three scores AZD2014 order of every group except group A were not different obviously (p > 0.05). On day 9 the scores of group C, group D were lower

than group E and group

B (p < 0.05), where there was not statistic difference between group C and group D or between group B and group F (p > 0.05). On day 14 the scores of group C, group D, group E, group F were lower than group B (p < 0.05). Among them the score of group F were highest (p < 0.05), group E second (p < 0.05), group C third selleck chemicals (p < 0.05), and the score of group D was lowest (p < 0.05). Conclusion: MSCs, TNFR II-IgG, mesalazine can significantly improve scores of DAI, CMDI, TDI of rats with colitis induced by TNBS. MSCs is the best, TNFR II-IgG is second, and mesalazine is third. Key Word(s): 1. MSCs; 2. TNFR II:IgG; 3. Mesalazine; 4. IBD; Presenting Author: SUMEI SHA Additional Authors: BIN XU, NI WEI, HUI YAN, SIJUN HU, KAICHUN WU Corresponding Author: KAICHUN WU Affiliations: Fourth Military Medical University Objective: Clinical and experimental observations in animal models indicate that intestinal commensal bacteria are involved in the initiation and amplification of Crohn’s disease (CD). Identification of adherent-invasive Escherichia coli (AIEC) strains in CD patients offers an opportunity to characterize the pathogenesis of microbial-induced intestinal inflammation. Previous studies have focused on the invasive phenotype of AIEC and the ability to replicate and survive in phagocytes. However, the precise mechanisms by which these newly identified microbes penetrate the epithelial lining remain to be clarified.

A combination

algorithm was developed and validated prospectively in 170 CHC additional patients. Results:  Epithelial membrane antigen at 130 kDa was identified, purified and quantified in sera of CHC patients using ELISA. Based on these encouraging results, we purified and developed a direct ELISA for the quantitation of EMA in sera of CHC. MDA selected a score for the prediction of significant liver fibrosis patients based on measurements of EMA, aspartate aminotransferase to platelet ratio index and albumin. Areas under the ROC curves (AUC) of the score for the three biomarkers were 0.82 for patients with liver fibrosis (F1–F4), 0.86 for significant liver fibrosis (F2–F4), 0.87 for advanced liver fibrosis (F3–F4) and 0.86 for liver cirrhosis (F4). The results of the validation study Palbociclib manufacturer demonstrated that (74%) of patients could have avoided liver biopsy. Conclusion:  This score was validated for the prediction of liver fibrosis stages and may minimize the need for liver biopsy. “
“Aim:  To evaluate the efficacy of reduction therapy of natural human interferon (IFN)-β and ribavirin in elderly patients with hepatitis C virus (HCV) genotype 1b and high viral load who had complications of anemia, low bodyweight (<50 kg), diabetes mellitus and/or hypertension.

Methods:  selleck products Inclusion criteria were age of 65 years or older, HCV genotype 1b, and serum HCV RNA level of 5.0 logIU/mL or higher. A total of 23 subjects with hemoglobin level of less than 13 g/dL, low bodyweight, diabetes mellitus and/or hypertension were enrolled in this study (reduction-dose group). IFN-β was administrated i.v. at a dose of 6 million units daily for 4 weeks initially, followed by three times a week for 44 weeks. Ribavirin was given daily for 48 weeks at a decreased dose of one tablet per day compared to the ordinary dose described based on bodyweight. As a control, another 22 patients without anemia, low bodyweight and/or complications treated with the standard dose of ribavirin (standard-dose group) were enrolled. Results:  Patients’ rates with further dose reduction or

discontinuation of treatment was 26.1% (6/23) in the reduction-dose group and 77.3% (17/22) in the standard-dose group. The sustained virological response find more (SVR) was 39.1% (9/23) in the reduction-dose group and 27.3% (6/22) in the standard-dose group (P = 0.404). Based on genetic variations near the IL28B gene (rs8099917), SVR was 44.1% (15/34) in patients with TT and 0% (0/11) in patients with TG (P = 0.008). Conclusion:  The reduction therapy of IFN-β and ribavirin in elderly HCV patients with genotype 1b, high viral load, IL28B gene (rs8099917) of TT who had complications of anemia, low bodyweight, diabetes mellitus and/or hypertension is one possible selection of treatment. “
“Routine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BECs).

A combination

algorithm was developed and validated prospectively in 170 CHC additional patients. Results:  Epithelial membrane antigen at 130 kDa was identified, purified and quantified in sera of CHC patients using ELISA. Based on these encouraging results, we purified and developed a direct ELISA for the quantitation of EMA in sera of CHC. MDA selected a score for the prediction of significant liver fibrosis patients based on measurements of EMA, aspartate aminotransferase to platelet ratio index and albumin. Areas under the ROC curves (AUC) of the score for the three biomarkers were 0.82 for patients with liver fibrosis (F1–F4), 0.86 for significant liver fibrosis (F2–F4), 0.87 for advanced liver fibrosis (F3–F4) and 0.86 for liver cirrhosis (F4). The results of the validation study this website demonstrated that (74%) of patients could have avoided liver biopsy. Conclusion:  This score was validated for the prediction of liver fibrosis stages and may minimize the need for liver biopsy. “
“Aim:  To evaluate the efficacy of reduction therapy of natural human interferon (IFN)-β and ribavirin in elderly patients with hepatitis C virus (HCV) genotype 1b and high viral load who had complications of anemia, low bodyweight (<50 kg), diabetes mellitus and/or hypertension.

Methods:  Cobimetinib price Inclusion criteria were age of 65 years or older, HCV genotype 1b, and serum HCV RNA level of 5.0 logIU/mL or higher. A total of 23 subjects with hemoglobin level of less than 13 g/dL, low bodyweight, diabetes mellitus and/or hypertension were enrolled in this study (reduction-dose group). IFN-β was administrated i.v. at a dose of 6 million units daily for 4 weeks initially, followed by three times a week for 44 weeks. Ribavirin was given daily for 48 weeks at a decreased dose of one tablet per day compared to the ordinary dose described based on bodyweight. As a control, another 22 patients without anemia, low bodyweight and/or complications treated with the standard dose of ribavirin (standard-dose group) were enrolled. Results:  Patients’ rates with further dose reduction or

discontinuation of treatment was 26.1% (6/23) in the reduction-dose group and 77.3% (17/22) in the standard-dose group. The sustained virological response selleck chemical (SVR) was 39.1% (9/23) in the reduction-dose group and 27.3% (6/22) in the standard-dose group (P = 0.404). Based on genetic variations near the IL28B gene (rs8099917), SVR was 44.1% (15/34) in patients with TT and 0% (0/11) in patients with TG (P = 0.008). Conclusion:  The reduction therapy of IFN-β and ribavirin in elderly HCV patients with genotype 1b, high viral load, IL28B gene (rs8099917) of TT who had complications of anemia, low bodyweight, diabetes mellitus and/or hypertension is one possible selection of treatment. “
“Routine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BECs).

Ucp2-null mice, however, were sensitive to APAP-induced hepatotoxicity despite activation of PPARα with Wy-14,643. Protection against hepatotoxicity by UCP2-induction through activation of PPARα is associated with decreased APAP-induced c-jun and c-fos expression, find more decreased phosphorylation of JNK and c-jun, lower mitochondrial H2O2 levels, increased mitochondrial glutathione in liver, and decreased levels of circulating fatty acyl-carnitines. These studies indicate that the PPARα target gene UCP2 protects against elevated reactive oxygen species generated during drug-induced hepatotoxicity and suggest that induction

of UCP2 may also be a general mechanism for protection of mitochondria during fatty acid β-oxidation. (HEPATOLOGY 2012;56:281–290) Peroxisome proliferator-activated receptor alpha (PPARα), a member of the nuclear receptor superfamily, controls the expression of a battery of genes involved in lipid homeostasis including those encoding peroxisomal and mitochondrial enzymes that carry out fatty acid catabolism. PPARα is mainly expressed in organs that are critical in fatty acid catabolism, such as liver, heart, and kidney.1-3 Perhaps the most critical role of PPARα is to modulate hepatic fatty acid catabolism. In untreated mice, PPARα controls constitutive expression of selleck chemicals mitochondrial

fatty acid β-oxidation enzymes.4 During periods of starvation in mice check details PPARα is activated, resulting in induction of both mitochondrial and peroxisomal fatty acid catabolism.5 Notably, in the course of spontaneous and ligand-induced activation of fatty acid catabolism excess H2O2 is produced as a byproduct of induction of peroxisomal acyl-CoA oxidase. Reactive oxygen species (ROS) are also produced during mitochondrial fatty acid β-oxidation. Although this increase in H2O2 is dealt with in part by catalase, glutathione peroxidase, and manganese superoxide dismutase, the cellular responses to ROS are saturated upon the massive activation of fatty

acid catabolism that occurs after ligand activation of PPARα. Consequently, increased PPARα activity during accelerated fatty acid catabolism is associated with increased expression of free-radical scavengers such as catalase and Cu/Zn dismutase6 and mitochondrial uncoupling proteins (UCPs) that may serve to reduce mitochondrial ROS levels.7, 8 Both direct and indirect effects suggest that PPARα may serve a protective role to combat the deleterious side effects of fatty acid catabolism, thus preserving, in particular, mitochondrial function. Increased ROS levels are frequently associated with hepatotoxicity produced by overdose of drugs such as acetaminophen (APAP). APAP, the most common nonprescription analgesic used for pain relief and antipyresis, is a representative compound that causes liver toxicity upon overdose and is a significant public health concern due to occasional overdose in children and adults.

In fact, in the study by Everhart et al.,13 obesity was significantly associated on univariate analysis with the development of outcomes (histological and/or clinical). The mechanism underlying the association between obesity and the development of clinical decompensation in cirrhosis is unknown. In our study, 1-year changes in portal pressure (as determined by HVPG) were significantly different among BMI groups, with HVPG decreasing significantly in normal weight and overweight patients but not in obese patients (in whom it showed a slight, not statistically significant increase) (Fig. 2). HVPG failed to decrease in obese patients despite

the fact that half of them received a potent nonselective beta-blocker (timolol).20 Moreover, only a minority of obese patients had a satisfactory hemodynamic response (HVPG decrease ≥10%) at 12 months. This observation suggests that check details the mechanism

by which obesity leads to a greater incidence of clinical decompensation RG7204 order is, at least in part, due to an increase in HVPG, as portal hypertension is responsible for the clinical complications that define this late stage of cirrhosis. In this regard it is worth noting that adipose tissue in obesity is known to acquire a proinflammatory, profibrogenic, and proangiogenic phenotype resulting in the production of adipokines and cytokines (leptin, interleukin (IL)-1 and tumor necrosis factor alpha)21-23 with deleterious vascular effects on hepatic inflammation, fibrogenesis, and angiogenesis, which may mediate a further worsening of intrahepatic resistance and portal hypertension.24, 25 From an epidemiologic point of view, it is interesting to note that over two-thirds of our patients with compensated cirrhosis were

overweight or obese and that this proportion is similar to that of the general population both in Europe and in the US.4 It could therefore be predicted that, as has been occurring in the general population, obesity selleck compound will increase further among patients with compensated cirrhosis. With this perspective and given the increased risk of clinical decompensation in obese patients with cirrhosis, the implementation of measures aimed at reducing obesity in patients with chronic liver diseases should be considered a priority. From a clinical point of view our findings have important implications. Up to now the only modifiable lifestyle-associated risk factor for decompensation in cirrhosis was alcohol ingestion in patients with alcoholic cirrhosis. In a similar way, our data suggest that overweight plays an important and independent role in the progression of compensated to decompensated cirrhosis, and might become a new nonpharmacological target for preventing clinical events in this population.

In fact, in the study by Everhart et al.,13 obesity was significantly associated on univariate analysis with the development of outcomes (histological and/or clinical). The mechanism underlying the association between obesity and the development of clinical decompensation in cirrhosis is unknown. In our study, 1-year changes in portal pressure (as determined by HVPG) were significantly different among BMI groups, with HVPG decreasing significantly in normal weight and overweight patients but not in obese patients (in whom it showed a slight, not statistically significant increase) (Fig. 2). HVPG failed to decrease in obese patients despite

the fact that half of them received a potent nonselective beta-blocker (timolol).20 Moreover, only a minority of obese patients had a satisfactory hemodynamic response (HVPG decrease ≥10%) at 12 months. This observation suggests that Selleck BMS-777607 the mechanism

by which obesity leads to a greater incidence of clinical decompensation HM781-36B chemical structure is, at least in part, due to an increase in HVPG, as portal hypertension is responsible for the clinical complications that define this late stage of cirrhosis. In this regard it is worth noting that adipose tissue in obesity is known to acquire a proinflammatory, profibrogenic, and proangiogenic phenotype resulting in the production of adipokines and cytokines (leptin, interleukin (IL)-1 and tumor necrosis factor alpha)21-23 with deleterious vascular effects on hepatic inflammation, fibrogenesis, and angiogenesis, which may mediate a further worsening of intrahepatic resistance and portal hypertension.24, 25 From an epidemiologic point of view, it is interesting to note that over two-thirds of our patients with compensated cirrhosis were

overweight or obese and that this proportion is similar to that of the general population both in Europe and in the US.4 It could therefore be predicted that, as has been occurring in the general population, obesity selleck kinase inhibitor will increase further among patients with compensated cirrhosis. With this perspective and given the increased risk of clinical decompensation in obese patients with cirrhosis, the implementation of measures aimed at reducing obesity in patients with chronic liver diseases should be considered a priority. From a clinical point of view our findings have important implications. Up to now the only modifiable lifestyle-associated risk factor for decompensation in cirrhosis was alcohol ingestion in patients with alcoholic cirrhosis. In a similar way, our data suggest that overweight plays an important and independent role in the progression of compensated to decompensated cirrhosis, and might become a new nonpharmacological target for preventing clinical events in this population.

The investigators then generated reporter HEALs by transducing lentiviruses expressing firefly luciferase under the control of the albumin promoter into HEP/FIB+TMNK1 cultures, and the encapsulated HEALs were implanted at an intraperitoneal (IP) site in athymic nude mice. Bioluminescence

imaging showed that the IP site could support the HEALs. Albumin promoter activity was maintained for several weeks, and human albumin and alpha-1-antitrypsin were secreted in the mouse sera. HEALs were reproducibly engrafted (91.6% of 131 mice transplanted) and microcomputed GSK2118436 purchase tomography angiography of extracted HEALs confirmed host vessel recruitment to, around, and inside the implant. HEAL-humanized mice could be rapidly and reproducibly generated from fresh and also cryopreserved hepatocytes. Moreover, unlike humanized chimeric mouse models, HELAs were maintained in immunocompetent and non-liver-injury mice for up to 8 days. HEAL-humanized mice expressed various human CYPs. Because major drug metabolites can be missed in standard animal models because of differences in drug-metabolism pathways among species, the investigators assessed whether the mice

could be used for the identification of major metabolites. Debrisoquine (DB) is a CYP2D6 substrate converted to 4-hydroxydebrisoquined (4-OHDB) in humans, but not in mice. 2 In fact, HEAL-humanized mice metabolized DB to 4-OHDB. More important, CYP2D6 is responsible for the metabolism of 25% of known drugs and its highly polymorphic nature contributes to significant interindividual this website variability. 15 The investigators prepared HEALs from two donors with different Fer-1 order levels of CYP2D6 and compared the ability of mice harboring the HEALs to metabolize DB. Mice with HEALs from the donor with lower levels of CYP2D6 metabolized DB less efficiently than those with HEALS from the donor with higher expression levels. Thus, HEAL-humanized mice can be used to detect breakdown products of drugs, which are missed

in standard mouse models. Drug-drug interactions are critical determinants of drug efficacy and safety because of the potential for drugs to alter the therapeutic or toxic effect of concomitantly administered compounds. Finally, the investigators explored the utility of the humanized mice for modeling toxic drug-drug interactions in vivo. Mice were first given rifampin (RIF) and then a therapeutic dose of acetoaminophen (APAP), a hepatotoxin at a high dose because of the CYP-mediated formation of N-acetyl-p-benzoquinone (NAPQI). 16 Although mice were resistant to RIF+APAP as a result of species-specific drug-drug interaction and HEAL-humanized mice given either RIF and APAP alone showed no sign of liver injury, HEAL-humanized mice given RIF+APAP showed evidence of human hepatocellular injury. Thus, HEAL-humanized mice can be used for screening hepatotoxic drug-drug combinations and doses invivo.

Knockdown of PPARβ Angiogenesis inhibitor clearly inhibited MAT2A expression as well as transcriptional activity. In culture-activated primary rat HSCs that exhibit an induction of PPARβ,3

silencing this gene inhibited MAT2A expression. This analysis established that PPARβ is a positive regulator of the MAT2A gene during HSC activation. Forced expression of MAT2A in RSG-treated cells reverses the quiescent state of HSCs by lowering the expression of PPARγ and concomitantly inducing PPARβ and the activation marker, α-SMA. These findings imply a reciprocal regulation between PPARs and MAT2A during quiescence and activation. Our previous work has shown that MAT2A knockdown reduces HSC activation, and the overexpression findings support the silencing data.15 Forced expression of MAT2A also lowered C/EBPβ protein levels, but we did not see a significant modulation of MAT2A when C/EBPβ reserves were altered. Hence, in quiescent and activated HSCs, PPARs appear to be the major modulators of MAT2A transcription, and MAT2A deregulates PPARs and other proteins during HSC activation. In conclusion, we have unraveled an important mechanism of transcriptional regulation of the MAT2A gene by two PPAR proteins that occupy the same binding site on the MAT2A promoter. In quiescent HSCs, the PPARγ subtype acts as a negative regulator of MAT2A transcription. During HSC activation, CH5424802 a dramatic reduction in PPARγ expression

and activity releases the inhibitory tone that this transcription factor exerts on MAT2A and allows positive regulators like PPARβ to bind to the MAT2A PPRE and induce the expression of this gene. MAT2A is the only SAM-synthesizing enzyme in HSCs and is a strong determinant of HSC activation and proliferation. Therefore, multiple levels of control of this gene may exist in HSCs apart from those described in this work. Identifying other novel factors that control MAT2A both transcriptionally and posttranscriptionally in HSCs is a subject of future investigation. Our sincere thanks go to Dr. Shelly Lu for expert advice and guidance. Additional Supporting Information may be found in the online version of this article.

“
“Liver fibrosis is a common selleck inhibitor pathway leading to cirrhosis. Cilostazol, a clinically available oral phosphodiesterase-3 inhibitor, has been shown to have antifibrotic potential in experimental non-alcoholic fatty liver disease. However, the detailed mechanisms of the antifibrotic effect and its efficacy in a different experimental model remain elusive. Male C57BL/6J mice were assigned to five groups: mice fed a normal diet (groups 1 and 2); 0.1% or 0.3% cilostazol-containing diet (groups 3 and 4, respectively); and 0.125% clopidogrel-containing diet (group 5). Two weeks after feeding, groups 2–5 were intraperitoneally administered carbon tetrachloride (CCl4) twice a week for 6 weeks, while group 1 was treated with the vehicle alone.