We confirmed CD49f as a gallbladder stem cell marker by LDAs and index sorts from primary gallbladder. EpCAM+CD49fhi cells have a significantly higher CFU readout relative to EpCAM+CD49flo cells. The low enrichment in CFU readout indicates that additional markers are required to further purify stem cells, such that single cells can be isolated and expanded.31 Therefore,

expression of EpCAM and CD49f enriches, but does not select for stem cells. All gallbladder epithelial cells expanded invitro were EpCAM+CD49f+. However, these cells exhibited morphological heterogeneity at first expansion, forming flat and glandular colonies. Interestingly, none of the glandular colonies and only a fraction of the flat colonies were capable of serial passage. It appears that the EpCAM+CD49fhi population in primary gallbladder is itself heterogeneous, with only a subpopulation of cells capable of self-renewal. We could not identify Cobimetinib supplier any additional markers to select for this specific subpopulation directly from primary tissue and, therefore, characterized the stemness of the EpCAM+CD49f+ cells expanded past p0. We determined that the expanded EpCAM+CD49f+ cells can self-renew clonogenically. However, defined protocols for gallbladder epithelial

cell differentiation do not exist. In the past, researchers have used collagen-gel sandwich culture to observe cyst morphogenesis with rabbit gallbladder epithelial cells.32, 33 The collagen gel is supplemented with exogenous growth factors, such as epidermal growth factor (EGF) and transforming growth factor (TGF)β1. We postulate Doxorubicin that our 3D culture system is similar to collagen gel culture, in that Matrigel is an appropriate growth factor containing extracellular matrix that supports morphogenesis. Cyst formation in our culture was similar in morphology and ultrastructure to that observed

before.32, 33 We also observed dye transport reminiscent of a transport function of the gallbladder. In addition, we observed similar morphogenesis in vivo after transplantation. We chose an ectopic location, because engraftment in the native gallbladder would be technically challenging and the subcutaneous space has been shown to engraft human gallbladder cells.26 Lee et al.34 have shown that gallbladder cells can engraft into the MCE native liver of severe combined immunodeficiency mice. However, engraftment was significant only with tremendous injury to the liver (e.g., retrorsine and partial hepatectomy or carbon tetrachloride treatment) and required very large numbers of cells. For these reasons, we concluded that subcutaneous, rather than liver, engraftment would be a more apt invivo assay. In our hands, the EpCAM+CD49f+ cells only engraft in the short term (2 weeks post-transplantation). This short-term engraftment might be the result of a lack of growth stimulus in the recipient. Also, under physiological conditions, the rate of cell proliferation in the gallbladder epithelium is low.

We confirmed CD49f as a gallbladder stem cell marker by LDAs and index sorts from primary gallbladder. EpCAM+CD49fhi cells have a significantly higher CFU readout relative to EpCAM+CD49flo cells. The low enrichment in CFU readout indicates that additional markers are required to further purify stem cells, such that single cells can be isolated and expanded.31 Therefore,

expression of EpCAM and CD49f enriches, but does not select for stem cells. All gallbladder epithelial cells expanded invitro were EpCAM+CD49f+. However, these cells exhibited morphological heterogeneity at first expansion, forming flat and glandular colonies. Interestingly, none of the glandular colonies and only a fraction of the flat colonies were capable of serial passage. It appears that the EpCAM+CD49fhi population in primary gallbladder is itself heterogeneous, with only a subpopulation of cells capable of self-renewal. We could not identify PLX3397 concentration any additional markers to select for this specific subpopulation directly from primary tissue and, therefore, characterized the stemness of the EpCAM+CD49f+ cells expanded past p0. We determined that the expanded EpCAM+CD49f+ cells can self-renew clonogenically. However, defined protocols for gallbladder epithelial

cell differentiation do not exist. In the past, researchers have used collagen-gel sandwich culture to observe cyst morphogenesis with rabbit gallbladder epithelial cells.32, 33 The collagen gel is supplemented with exogenous growth factors, such as epidermal growth factor (EGF) and transforming growth factor (TGF)β1. We postulate Saracatinib that our 3D culture system is similar to collagen gel culture, in that Matrigel is an appropriate growth factor containing extracellular matrix that supports morphogenesis. Cyst formation in our culture was similar in morphology and ultrastructure to that observed

before.32, 33 We also observed dye transport reminiscent of a transport function of the gallbladder. In addition, we observed similar morphogenesis in vivo after transplantation. We chose an ectopic location, because engraftment in the native gallbladder would be technically challenging and the subcutaneous space has been shown to engraft human gallbladder cells.26 Lee et al.34 have shown that gallbladder cells can engraft into the MCE native liver of severe combined immunodeficiency mice. However, engraftment was significant only with tremendous injury to the liver (e.g., retrorsine and partial hepatectomy or carbon tetrachloride treatment) and required very large numbers of cells. For these reasons, we concluded that subcutaneous, rather than liver, engraftment would be a more apt invivo assay. In our hands, the EpCAM+CD49f+ cells only engraft in the short term (2 weeks post-transplantation). This short-term engraftment might be the result of a lack of growth stimulus in the recipient. Also, under physiological conditions, the rate of cell proliferation in the gallbladder epithelium is low.

Recently, high-fat diet (HFD) induced steatosis was thought

to be associated with the depletion of hepatic regulatory T cells (Tregs) and the adoptive transfer of Tregs decreased inflammation in HFD-fed mice. Glycyrrhizin (GL), a natural triterpene in clinical treatment of patients with chronic liver disease, Roxadustat in vitro can significantly reduce free fatty acid (FFA)/ HFD induced hepatic lipotoxicity. Methods: For induction of NASH, mice were fed with a methionin–choline-deficient (MCD) diet for 8 weeks. Control mice received a standard diet containing 10% fat. All diets were γ-irradiated. Development of liver injury was followed by intraperitoneal administration of GL or vehicle control (saline) two times a week for the last 4 weeks on the diet in MCD mice. The analysis of hepatic and splenic CD4+T cells phenotypes and the preparation of splenic CD4+T,

CD4+CD25+ and CD4+CD25-T cells were done by flow cytometry. The detection of PPAR-γ was done by Western blot and T-cell cytokines were measured by ELISA. T-cell proliferation assay was tested by the MTT method and cell apoptosis was analyzed using the Annexin V-FITC Apoptosis Detection Kit. Purified splenic CD4+CD25+T cells from MCD-fed mice or GL treated MCD-fed mice were collected and co-cultured with splenic CD4+CD25-T cells from control mice. Furthermore, specific inhibitor of PPAR-γ (GW9662) or agonist of PPAR-γ was also added along with GL treatment to observe whether the effects of GL Ivacaftor datasheet were dependent on PPAR-γ signaling or not. Results: GL alleviated MCD-induced liver injury by decreasing ALT and AST levels in serum to normalization

nearly in time and dose dependent manners. GL also reduced hepatic inflammatory cell infiltrations, hepatic lipid overloading and the NAFLD activity in MCD-fed mice. GL altered the proportion of hepatic and splenic CD4+T cells and cytokines secretion in MCD-fed mice, which showed the prevalence MCE of Tregs and decreased proportion of Th17 cells. GL promoted the apoptosis of hepatic and splenic Th1 and Th17 cells but relatively inhibited which of Tregs. GL enhanced the level of PPARγ, which correlated with the enhanced proportion of serum CD4+CD25+T cells. In vitro experiment, PPARγ signaling participated in the GL-induced proliferation of splenic nTregs. GL enhanced the inhibitory effect of splenic nTregs on Teffs (CD4+CD25-T cells), which was dependent on PPAR-γ. Furthermore, GL promoted the production of iTregs and altered the proliferation, apoptosis and cytokines secretion of iTregs Conclusion: These results provide evidence that GL, which has excellent anti-inflammatory characteristics, amelioration of hepatic injury and definite lipidlowering properties, and may be capable of alleviating the progression of NASH. The therapeutic effects of GL partly contribute to the induction of Tregs and the enhanced modulatory functions of Tregs, and furthermore, PPAR-γ signaling may be involved in the modulatory mechanism of GL. Key Word(s): 1. Glycyrrhizin; 2.

Recently, high-fat diet (HFD) induced steatosis was thought

to be associated with the depletion of hepatic regulatory T cells (Tregs) and the adoptive transfer of Tregs decreased inflammation in HFD-fed mice. Glycyrrhizin (GL), a natural triterpene in clinical treatment of patients with chronic liver disease, check details can significantly reduce free fatty acid (FFA)/ HFD induced hepatic lipotoxicity. Methods: For induction of NASH, mice were fed with a methionin–choline-deficient (MCD) diet for 8 weeks. Control mice received a standard diet containing 10% fat. All diets were γ-irradiated. Development of liver injury was followed by intraperitoneal administration of GL or vehicle control (saline) two times a week for the last 4 weeks on the diet in MCD mice. The analysis of hepatic and splenic CD4+T cells phenotypes and the preparation of splenic CD4+T,

CD4+CD25+ and CD4+CD25-T cells were done by flow cytometry. The detection of PPAR-γ was done by Western blot and T-cell cytokines were measured by ELISA. T-cell proliferation assay was tested by the MTT method and cell apoptosis was analyzed using the Annexin V-FITC Apoptosis Detection Kit. Purified splenic CD4+CD25+T cells from MCD-fed mice or GL treated MCD-fed mice were collected and co-cultured with splenic CD4+CD25-T cells from control mice. Furthermore, specific inhibitor of PPAR-γ (GW9662) or agonist of PPAR-γ was also added along with GL treatment to observe whether the effects of GL Selleckchem Ceritinib were dependent on PPAR-γ signaling or not. Results: GL alleviated MCD-induced liver injury by decreasing ALT and AST levels in serum to normalization

nearly in time and dose dependent manners. GL also reduced hepatic inflammatory cell infiltrations, hepatic lipid overloading and the NAFLD activity in MCD-fed mice. GL altered the proportion of hepatic and splenic CD4+T cells and cytokines secretion in MCD-fed mice, which showed the prevalence medchemexpress of Tregs and decreased proportion of Th17 cells. GL promoted the apoptosis of hepatic and splenic Th1 and Th17 cells but relatively inhibited which of Tregs. GL enhanced the level of PPARγ, which correlated with the enhanced proportion of serum CD4+CD25+T cells. In vitro experiment, PPARγ signaling participated in the GL-induced proliferation of splenic nTregs. GL enhanced the inhibitory effect of splenic nTregs on Teffs (CD4+CD25-T cells), which was dependent on PPAR-γ. Furthermore, GL promoted the production of iTregs and altered the proliferation, apoptosis and cytokines secretion of iTregs Conclusion: These results provide evidence that GL, which has excellent anti-inflammatory characteristics, amelioration of hepatic injury and definite lipidlowering properties, and may be capable of alleviating the progression of NASH. The therapeutic effects of GL partly contribute to the induction of Tregs and the enhanced modulatory functions of Tregs, and furthermore, PPAR-γ signaling may be involved in the modulatory mechanism of GL. Key Word(s): 1. Glycyrrhizin; 2.

The 2/3 PH in C57BL/6 mice caused a decrease in Axin1 expression that was detectable at 12 hours, lowest between 24 and 36 hours, and began to return at 48 hours after surgery (Fig. S8A,B). The expression changes in Axin1 suggest that Axin1 might be inhibited by lncRNA-LALR1 during liver regeneration. Taken together, these data showed that lncRNA-LALR1 activated the Wnt/β-catenin pathway in hepatocytes. LncRNA-LALR1 decreased the expression of Axin1, and the stability of the β-catenin destruction complex receded, which led to the decline in the levels of phosphorylated β-catenin (inactive); active β-catenin could no longer AG-014699 chemical structure stay bound and was released. This monomeric form

of β-catenin binds to proteins such as T-cell factor-4 (TCF-4) and lymphoid enhancement factor (LEF) and translocates to the nucleus to control the transcription of target genes, including c-myc and cyclin D1. Finally, lncRNA-LALR1 facilitated mouse cell cycle progression and hepatocyte proliferation (Fig. 7). We wondered whether the mechanism of lncRNA-LALR1 activates the Wnt/β-catenin pathway by suppressing Axin1. We performed a computational screen (http://jaspar.genereg.net; Staurosporine CTCFBSDB2.0[19]) and found a CTCF binding site within the AXIN1 promoter region (−1,892 bp upstream of the transcription start site of AXIN1). Recent studies have reported

that the transcription factor CTCF can bind to the promoter region of target genes and inhibit their expression.[20] There was no significant difference in the CTCF mRNA and protein levels in lncRNA-LALR1-up-regulated CCL-9.1 cells compared to those in the control cells (data not shown). To determine whether lncRNA-LALR1 could change the binding of CTCF to the AXIN1 promoter region, medchemexpress we performed ChIP analysis in lncRNA-LALR1-up-regulated CCL-9.1 cells and lncRNA-LALR1-down-regulated BNL CL.2 cells. We observed that overexpression of lncRNA-LALR1 increased the binding of CTCF at the AXIN1 promoter region in CCL-9.1 cells, and the binding declined in lncRNA-LALR1-down-regulated BNL CL.2 cells (Fig. 8A). These results confirmed that lncRNA-LALR1 could increase the binding of CTCF to the AXIN1 promoter region in hepatocytes. In addition, we

tested whether lncRNA-LALR1 could associate with CTCF. We performed RIP with an antibody against CTCF from extracts of BNL CL.2 cells and CCL-9.1 cells. We observed significant enrichment of lncRNA-LALR1 with the CTCF antibody compared with the nonspecific IgG control antibody (Fig. 8B). Next, we performed an in vitro RNA pulldown to validate the association between lncRNA-LALR1 and CTCF in BNL CL.2 cells and CCL-9.1 cells. This analysis confirmed that lncRNA-LALR1 physically associated with CTCF in vitro (Fig. 8C). Together, the RIP and RNA pulldown results demonstrate a specific association between CTCF and lncRNA-LALR1. The expression level of Axin1 was not statistically different in lncRNA-LALR1-down-regulated BNL CL.2 cells and lncRNA-LALR1-up-regulated CCL-9.

Both analyses show that whereas the use of sorafenib was associated with an increased risk of bleeding in HCC, this was primarily for lower-grade events and similar in magnitude to the risk encountered in RCC. Although the nature of these low-grade events for the most part were not characterized, they were defined as grade 1 or 2, meaning that by Common Terminology Criteria for Adverse Events (CTCAE) definition they did not require transfusion or endoscopic intervention. We also set out to describe the heterogeneity with regard

to the eligibility criteria employed across HCC trials for study entry, as these are reflective of Selleckchem CT99021 baseline risk and are nonstandardized in HCC compared to other solid tumors. A major drawback of this analysis is the fact that only four of the HCC studies contained a control arm. When we confined our analysis to randomized studies—all of which involved sorafenib—there buy C59 wnt was a significant (P = 0.04) increase in the odds of bleeding events of (OR 1.73; 95% CI 1.02, 2.94) associated with sorafenib compared to control, although this increased risk appeared to be confined to lower-grade events. To ascertain whether this

was a disease-specific effect we also analyzed the hemorrhagic risk in studies evaluating sorafenib in RCC and found the risk to be similarly increased (OR 1.92; 95% CI 1.30, 2.85), suggesting that this is not necessarily greater in HCC patients beyond the effect of the drug itself. Given that the majority of studies evaluating an antiangiogenic agent in HCC are single-arm, nonrandomized phase 2 trials it is very difficult to estimate the overall bleeding risk in these studies, especially given the heterogeneity of treatments administered. To address this, at least partially, we performed a comparative analysis with a group of single-arm phase 2 studies that did not include therapy considered antiangiogenic. We acknowledge the limitations of this approach, and certainly one cannot draw conclusions on causal effects from these uncontrolled studies evaluating heterogeneous agents. Because our outcome is one MCE of safety, however, we felt that the phase II single-arm studies could provide valid additional data. The results were instructive

in that patients with HCC taking part in these studies appeared to have a significantly increased risk of all-grade bleeding compared to non-antiangiogenic therapy. It must be emphasized, however, that sorafenib is the only approved agent for HCC. From a biological standpoint, although we do not know whether the benefit of sorafenib is predominantly related to its signal transduction inhibition versus its antiangiogenic properties, it seems likely—by association rather than direct proof—that the hemorrhagic risk is related to its anti-VEGF effect.9, 10 It is known that VEGF has an important role in the maintenance of architectural integrity within the endothelial cells of the microvasculature, inhibition of which may induce the increased risk of bleeding.

Both analyses show that whereas the use of sorafenib was associated with an increased risk of bleeding in HCC, this was primarily for lower-grade events and similar in magnitude to the risk encountered in RCC. Although the nature of these low-grade events for the most part were not characterized, they were defined as grade 1 or 2, meaning that by Common Terminology Criteria for Adverse Events (CTCAE) definition they did not require transfusion or endoscopic intervention. We also set out to describe the heterogeneity with regard

to the eligibility criteria employed across HCC trials for study entry, as these are reflective of GW-572016 cell line baseline risk and are nonstandardized in HCC compared to other solid tumors. A major drawback of this analysis is the fact that only four of the HCC studies contained a control arm. When we confined our analysis to randomized studies—all of which involved sorafenib—there www.selleckchem.com/products/c646.html was a significant (P = 0.04) increase in the odds of bleeding events of (OR 1.73; 95% CI 1.02, 2.94) associated with sorafenib compared to control, although this increased risk appeared to be confined to lower-grade events. To ascertain whether this

was a disease-specific effect we also analyzed the hemorrhagic risk in studies evaluating sorafenib in RCC and found the risk to be similarly increased (OR 1.92; 95% CI 1.30, 2.85), suggesting that this is not necessarily greater in HCC patients beyond the effect of the drug itself. Given that the majority of studies evaluating an antiangiogenic agent in HCC are single-arm, nonrandomized phase 2 trials it is very difficult to estimate the overall bleeding risk in these studies, especially given the heterogeneity of treatments administered. To address this, at least partially, we performed a comparative analysis with a group of single-arm phase 2 studies that did not include therapy considered antiangiogenic. We acknowledge the limitations of this approach, and certainly one cannot draw conclusions on causal effects from these uncontrolled studies evaluating heterogeneous agents. Because our outcome is one MCE公司 of safety, however, we felt that the phase II single-arm studies could provide valid additional data. The results were instructive

in that patients with HCC taking part in these studies appeared to have a significantly increased risk of all-grade bleeding compared to non-antiangiogenic therapy. It must be emphasized, however, that sorafenib is the only approved agent for HCC. From a biological standpoint, although we do not know whether the benefit of sorafenib is predominantly related to its signal transduction inhibition versus its antiangiogenic properties, it seems likely—by association rather than direct proof—that the hemorrhagic risk is related to its anti-VEGF effect.9, 10 It is known that VEGF has an important role in the maintenance of architectural integrity within the endothelial cells of the microvasculature, inhibition of which may induce the increased risk of bleeding.

In the absence of evidence-based treatment guidelines,

Ibrutinib this article presents 10 cases of difficult to control acute and surgical bleeding and offers consensus opinions regarding their management from a panel of experienced haemophilia treaters. “
“Congenital haemophilia is a rare and complex condition for which dedicated specialized and comprehensive care has produced measurable improvements in clinical outcomes and advances in patient management. Among these advances is the ability to safely perform surgery in patients with inhibitor antibodies to factors VIII and IX, in whom all but the most necessary of surgeries were once avoided due to the risk for uncontrollable Rucaparib molecular weight bleeding due to ineffectiveness of replacement therapy. Nevertheless, surgery continues to pose a major challenge in this relatively rare group of patients because of significantly higher costs than in patients without inhibitors, as well as a high risk for bleeding and other complications. Because of the concentration of expertise and experience, it is recommended that any surgery in patients with haemophilia and inhibitors be planned in conjunction

with a haemophilia treatment centre (HTC) and performed in a hospital that incorporates a HTC. Coordinated, standard pre-, intra- and postoperative assessments and planning are intended to optimize surgical outcome and utilization of resources, including costly factor concentrates and other haemostatic agents, while minimizing the risk for bleeding and other adverse consequences both during and after surgery. This article will review the special considerations for patients with inhibitors as they prepare for and move through surgery and recovery, with an emphasis on the roles and responsibilities of individual members of the multidisciplinary

team in facilitating this process. Congenital haemophilia, a rare and complex condition, requires a lifetime of specialized care. A network of haemophilia treatment centres (HTCs) has been established in many developed countries to provide dedicated comprehensive, 上海皓元医药股份有限公司 multidisciplinary care in a single setting [1]. In the United States, the provision of haemophilia care by these centres has led to an array of documented improved outcomes, including substantial reductions in hospital visits, health care costs, work and school absenteeism and even mortality [2, 3]. Even in developing countries with limited haemostatic treatment options, the establishment of local expertise via such initiatives as ‘twinning’ programmes has resulted in improvements in patient care [1]. Approximately 20–30% and 1–6% of patients with severe haemophilia A and B, respectively [4], develop inhibitory antibodies that render replacement therapy ineffective, potentially leading to life-threatening bleeding events.

In the absence of evidence-based treatment guidelines,

Selleckchem MS-275 this article presents 10 cases of difficult to control acute and surgical bleeding and offers consensus opinions regarding their management from a panel of experienced haemophilia treaters. “
“Congenital haemophilia is a rare and complex condition for which dedicated specialized and comprehensive care has produced measurable improvements in clinical outcomes and advances in patient management. Among these advances is the ability to safely perform surgery in patients with inhibitor antibodies to factors VIII and IX, in whom all but the most necessary of surgeries were once avoided due to the risk for uncontrollable Torin 1 research buy bleeding due to ineffectiveness of replacement therapy. Nevertheless, surgery continues to pose a major challenge in this relatively rare group of patients because of significantly higher costs than in patients without inhibitors, as well as a high risk for bleeding and other complications. Because of the concentration of expertise and experience, it is recommended that any surgery in patients with haemophilia and inhibitors be planned in conjunction

with a haemophilia treatment centre (HTC) and performed in a hospital that incorporates a HTC. Coordinated, standard pre-, intra- and postoperative assessments and planning are intended to optimize surgical outcome and utilization of resources, including costly factor concentrates and other haemostatic agents, while minimizing the risk for bleeding and other adverse consequences both during and after surgery. This article will review the special considerations for patients with inhibitors as they prepare for and move through surgery and recovery, with an emphasis on the roles and responsibilities of individual members of the multidisciplinary

team in facilitating this process. Congenital haemophilia, a rare and complex condition, requires a lifetime of specialized care. A network of haemophilia treatment centres (HTCs) has been established in many developed countries to provide dedicated comprehensive, medchemexpress multidisciplinary care in a single setting [1]. In the United States, the provision of haemophilia care by these centres has led to an array of documented improved outcomes, including substantial reductions in hospital visits, health care costs, work and school absenteeism and even mortality [2, 3]. Even in developing countries with limited haemostatic treatment options, the establishment of local expertise via such initiatives as ‘twinning’ programmes has resulted in improvements in patient care [1]. Approximately 20–30% and 1–6% of patients with severe haemophilia A and B, respectively [4], develop inhibitory antibodies that render replacement therapy ineffective, potentially leading to life-threatening bleeding events.

2 However, the current mode of treatment is not equally effective for all HCV genotypes and significant GDC-0973 molecular weight side effects are still observed. Efforts are currently being made to develop a combination of new direct-acting antivirals (DAAs) not leading to the emergence of escape

mutations and, if possible, free of IFN. First proofs of concept recently emerged from clinical trials demonstrating that combinations of DAAs can result in the cure of chronic HCV infection.3, 4 However, combinations of drugs targeting different steps of the viral life cycle, including virus entry, will likely improve viral response rates and therapeutic success. HCV is a small enveloped virus with a positive stranded RNA genome belonging to the Hepacivirus genus in the Flaviviridae family.5 Its genome encodes two envelope glycoproteins (E1 and E2), which play a key role in virus entry into the hepatocyte. However, as a result of its association with low- or very-low-density lipoproteins,6 the lipoprotein moiety can also play a role in the entry process of HCV particle. HCV entry is currently viewed as a complex multistep process, because a series of specific cellular entry factors have been shown to be essential in the early steps of the HCV life cycle.7 These molecules include the CYC202 scavenger receptor class B type 1 (SRB1), the tetraspanin CD81,

tight-junction proteins claudin 1 (CLDN1) and occludin (OCLN), and receptor tyrosine kinase-like epidermal growth factor receptor. After its interaction with entry factors at the cell surface, HCV particle is internalized by clathrin-mediated endocytosis.8 Importantly, as for several other viruses, HCV can also spread MCE公司 by direct cell-to-cell transfer.9, 10 3D, three-dimensional; Ab, antibody; BVDV, bovine viral diarrhea virus; CC50, 50% cytotoxic concentration; CI, combination index; CLD, chronic liver disease; CLDN1, claudin 1; CMFDA, 5-chloromethylfluorescein diacetate; CQ, chloroquine; DAAs, direct-acting antivirals; DMEM,

Dulbecco’s modified Eagle’s medium; DMSO, dimethyl sulfoxide; FCS, fetal calf serum; ffu, focus forming unit; FQ, ferroquine; gRNA, genomic RNA; HCV, hepatitis C virus; HCVcc, hepatitis C virus produced in cell culture; HCVpp, hepatitis C virus pseudoparticle; IC50, half-maximal inhibitory concentration; IC90, 90% inhibitory concentration; IF, immunofluorescence; IFN, interferon; JFH-1, Japanese fulminant hepatitis type 1; LT, liver transplantation; mAb, monoclonal Ab; OCLN, occludin; PE, phycoerythrin; Peg-IFN-α, pegylated interferon alpha; qRT-PCR, quantitative reverse-transcription polymerase chain reaction; RBV, ribavirin; SRB1, scavenger receptor class B type 1; YFV, yellow fever virus. Ferroquine (FQ; SSR97193) is a ferrocenic analog of chloroquine (CQ) that has been developed as a new antimalarial drug (Fig. 1A).