Type 1 RS: Starch granules surrounded by indigestible plant matrix Type 2 RS: Found in natural form as high amylose content starch in maize, rice etc. Type 3 RS: Crystallized starches made by unique cooking and cooling processes Type 4 RS: Starch chemically modified by esterification, crosslinking, or transglycosylation Celluloses Hemicelluloses Gums Pectins Xylans Mannans Glucans Mucilages Lactose Fructose Sorbitol Lactitol Mannitol Maltitol Xylitol Fructooligosaccharides Raffinose Stachyose Inulin Polydextrose (used in food industry) In the study[12] MK-1775 cited in the previous section, in which three enterotypes

of the human gut microbiota were identified, metabolic pathway analysis led to some interesting conclusions. It suggested that the microbes of enterotype 1-derived energy mainly from the fermentation of carbohydrates and proteins, as they were enriched for genes representing saccharolytic enzymes, galactosidases, hexosaminidases, proteases, and enzymes in the glycolysis and pentose phosphate pathways. Enterotypes 2 and 3 were considered to derive energy significantly from mucin degradation, although the latter probably also had potential to utilize carbohydrates by fermentation by virtue of the presence this website of significant numbers of Bacteroides species. Enterotype 1 was enriched in enzymes involved in biosynthesis

of biotin, riboflavin, pantothenate, and ascorbate while enterotype 2 was enriched in enzymes involved in biosynthesis of thiamine and folate. Starch degradation enzymes increased with age, consistent with changing dietary patterns. Two marker modules that correlated strongly with host body mass index were identified to be ATPase complexes, reinforcing a link between gut microbiota and energy nutrition state in the host. Between 10% and 20% of ingested dietary carbohydrates are resistant to small intestinal digestion. These non-digestible dietary carbohydrates (NDC) include certain forms of starch that are resistant to amylase

digestion (resistant starch [RS]) as well as non-starch polysaccharides (NSPs) (Table 1).[24, 25] The NSP include substances such as pectin that are substrates for colonic eltoprazine bacterial metabolism, and substances such as cellulose that are not fermented by the colonic bacteria. Non-digestible dietary carbohydrates enter the colon where RS and fermentable NSP are fermented by colonic bacteria to SCFA, lactate, and gases such as CO2, H2, and methane (Fig. 1).[26, 27] RS, primarily from cereals but also from raw banana and potato, is a very important substrate for colonic fermentation.[24, 27, 28] While many commonly eaten foods have a significant content of type 2 RS (i.e. naturally present in the food source), the method of cooking and eating may enhance RS content of the food.

Osmotic stress often results in cellular and photo-oxidative damage caused by accumulation of ROS (Peltzer et al. 2002). ROS attack a variety of biomolecules, resulting in enzyme inhibition, chlorophyll degradation, DNA damage, and lipid peroxidation, which may lead to irreparable metabolic dysfunction and cell death (Apel and Hirt 2004). Cellular defense systems against ROS include enzymatic scavenging through increased

activity of SOD, POD, catalase, ascorbate peroxidase, glutathione peroxidase, glutathione reductase, and peroxiredoxin (Mittler et al. 2004). Non-enzymatic defense systems include elevation of cellular proline, carotenoids, tocopherols, ascorbic acid, and glutathione. The defense systems triggered in cells Acalabrutinib solubility dmso vary from organism to organism (Takeda et al. 1995, Abd El-Baky et al. 2004). Numerous

studies on drought stress have been done with plants (Morgan 1984, Apel and Hirt 2004). Plants tend to accumulate specific substances for osmoregulation under osmotic stress (Morgan 1984). This allows cells to keep water even at low soil water potentials, so that the turgor pressure, metabolic activity, and growth of plants are maintained during prolonged water deficits (Hanson and Hits 1982). Recently, the establishment and use of BSCs to ameliorate desertification, to restore acrid or polluted lands, and to improve soil texture have received great interest (Yang et al. 2001, Jusu et al. 2004, Guo et al. 2008),

due to the fact that BSCs may increase soil aggregation and stability, thereby reducing wind and water erosion (Mazor et al. 1996, Eldridge and Kinnell 1997). BSCs click here would increase soil fertility by N- and C-fixations (Starks et al. 1981, Eldridge and Greene 1994, Lange et al. 1994). Numerous strains in BSCs are capable of tolerance or resistance to drought by maintaining a constant imbalance between the internal water content and external water availability. Nevertheless, in comparison with plants, less is known about ifenprodil drought-tolerance mechanisms in soil algae and cyanobacteria. To better understand the mechanism underlying drought stress injury in these organisms, we compared the physiological response of drought-tolerant soil species with non-tolerant ones. We also attempted to determine the key compounds responsible for the tolerance to drought stress and assessed organisms suitable for stabilizing bare soils. BSCs were collected from Hoyen Mountain (24°35′ N, 121°24′ E) that is situated in the middle of Taiwan. They were crushed and passed through 1.0 mm pore size sieve. Five grams of samples were suspended in 100 mL of sterile distilled water. Then, the mixtures were incubated under shaking in darkness for 2 h to get soil suspensions. Subsequently, 0.1 mL of the soil suspension was inoculated in 100 mL BG11 medium (Stanier et al. 1971) or Chlorella (NC) medium (Kuhl 1962) and illuminated under 75 mol photons · m−2 · s−1.

Conversely, curcumin-resistant cells exhibited a paradoxical response. Mechanistically, CSC-depleting activity was exerted by NF-kB mediated HDAC inhibition leading to down-regulation

of c-MYC and other key oncogenic targets. Co-administration of a class I and II HDAC inhibitor sensitized the curcumin-resistant cells to curcumin treatment. Further, integration of a predictive signature with our HCC database indicated that HCCs with progenitor cell features are most likely to respond to NF-kB inhibition. These data demonstrate that NF-kB inhibtion can specifically target CSC populations. check details Future investigations will determine the potential of combined inhibition of NF-kB signaling and HDAC for CSC-directed HCC therapy. Disclosures: Peter R. Galle – Advisory Committees or Review Panels: Bayer, BMS, Lilly, Daiichi, Jennerex;

Consulting: Medimmune; Grant/Research Support: Roche, Lilly; Speaking and Teaching: Bayer, BMS The following people have nothing to disclose: Jens U. Marquardt, Luis E. Gómez-Quiroz, Lucrecia O. Arreguin Camacho, Frederico Pinna, Yun-Han Lee, Mitsuteru Kitade, Jesper B. Andersen, Kai Breuhahn, Valentina M. Factor, Snorri S. Thorgeirsson Background: Cholangiocarcinoma (CCA) is a highly lethal neoplasm for which the currently R428 purchase available chemotherapeutic agents are suboptimal. Therefore there is an urgent need to develop novel effective therapies against this cancer. Sphin-gosine kinase-2 (Sk2) is essential for tumor

proliferation and survival. A recently developed first-in-class oral Sk2 specific inhibitor 3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyr-idin-4-ylmethyl)amide (ABC294640) displays antitumor activity in many cancer models. However, the role of Sk2 and the antitumor activity of its inhibitor ABC294640 have not been examined in CCA. Aim: To investigate the antitumor effect of ABC294640 in CCA. Methods: Real-time q-PCR was used to determine the expression level of Sk2 in different CCA cells and normal human cholangiocytes (H69). Brdu ELISA assay and clonogenic assay were used to assess cell proliferation. DAPI staining, Annexin V/PI staining, caspase 3, 8, 9 and PARP cleavage were used to assess apoptosis. Immunoblot-ing for microtubule-associated protein light chain 3 (LC3) and transmission electron microscopy were used to monitor autophagy. The combination buy Decitabine index (CI) of ABC294640 and sorafenib administered in combination was determined by the Chou-Ta-lalay method. Results: Sk2 mRNA expression is elevated in five established human CCA cell lines (WITT, HuCCT1, EGI-1, OZ and HuH28) and a new patient derived primary CCA cell line (LIV27) compared to H69 cells (p<0.01). Treatment with ABC294640 inhibited the proliferation of all six human CCA cell lines with an IC50 between 39.8UM and 55.6UM at 72h, which is similar to previous results in hepatocellular carcinoma cell lines. ABC294640 dose-dependently induced caspase cleavage and apoptosis.

Similar results were also reported by Ozkasap et al. [36] who demonstrated that H. pylori eradication significantly reduces the levels of hepcidin, possibly by increasing the response to iron therapy. On the other hand, Kim et al. [37] did not find any significant association between H. pylori infection and serum levels of prohepcidin, while this biomarker was decreased in patients with atrophic gastritis. Finally, the results of three recent studies did not support any association between H. pylori infection and IDA [38-40]; however, the occurrence of some biases, such as the exact definition of IDA or the absence of information concerning the specific gastric histologic

patterns shown by patients, may, in our Selleckchem Lumacaftor opinion, affect the results of studies performed on this important issue. The role of H. pylori on idiopathic thrombocytopenic purpura (ITP), via the modulation of Fcγ-receptor balance of monocytes/macrophages or molecular mimicry mechanisms between platelet and H. pylori peptides, is well defined [41]. A study by Payandeh et al. [42] clearly reported a significant beneficial effect of H. pylori eradication in patients with mild thrombocytopenia, but a poor response in patients with severe thrombo-cytopenia was noted. In a similar study, Teawtrakul et al. [43] showed a significant platelet count response

in approximately 80% of learn more adults with ITP after H. pylori eradication within a median time of 4 months. Nevertheless, some authors

reported negative findings. Samson et al. [44] did not show any significant difference between infected and noninfected patients concerning the platelet count, while Gan et al. [45] reported a low prevalence of H. pylori infection in patients with ITP and the absence of any significant effect of H. pylori eradication on the platelet count. Differences in the definition Org 27569 of ITP may be the cause of those findings, at least in our opinion. A meta-analysis by Shi et al. [46] conducted on patients with autoimmune thyroid disease (ATD) reported a significant role of H. pylori in Grave’s disease (GD), more than in Hashimoto’s thyroiditis (HT), with an additional increased risk in the case of infection sustained by CagA-positive strains. Another study by Aghili et al. [47] reported a significant epidemiological association between H. pylori infection and HT in patients from Iran. Similarly, Zekry et al. [48] demonstrated a significant association between H. pylori infection and autoimmune thyroiditis in patients affected by type 1 DM. An additional interesting study clearly showed a significant association between GD, CagA positivity, and negative HLA-DQA1 0201 or positive HLA-DQA1 0501 [49]. Finally, Jafarzadeh et al. [50] reported higher serum levels of rheumatoid factor and antinuclear antibodies in H.

We further investigated the positive correlation between CHD1L and TCTP in clinical specimens. TCTP expression was significantly correlated with CHD1L expression in these specimens (Spearmen correlation coefficient, 0.449; P < 0.0001; Fig. 1F), further indicating that CHD1L is able to up-regulate TCTP Ivacaftor expression. To determine the prevalence and clinical significance of TCTP in HCC, the correlation between overexpression

of TCTP and the clinicopathological features was investigated in a retrospective cohort of 118 HCC patients. As detected by qPCR, overexpression of TCTP (defined as a greater than 2-fold increase) was detected in 40.7% (48 of 118) of HCC cases. HCC tissues showed higher expression of TCTP than adjacent nontumor tissues (Wilcoxon signed rank test, P = 0.0336; Fig. 2A). Overexpression of TCTP in HCC tissues was

significantly associated with advanced tumor stage (P = 0.037; Table 1). To confirm our findings, immunohistochemical (IHC) staining of TCTP was conducted in paraffin sections from 20 patients with HCCs of different tumor stages (6 HCCs of stage I, 6 HCCs of stage II, and 8 HCCs of stage III). In 9 of 14 (57.1%) of advanced HCC cases (stage II and III), expression of TCTP was obviously higher Y 27632 in tumor tissues, as compared to their adjacent nontumor tissues (Fig. 2C), whereas 5 of 6 (83.3%) of stage I HCC tissues showed an expression pattern of TCTP similar to nontumor tissues (Fig. 2B). The prognostic significance of TCTP overexpression was also studied in this cohort of 108 patients with valid follow-up data. As a result, TCTP overexpression was significantly associated with shorter overall survival (OS) of patients (log rank = 4.495, P = 0.034; Fig. 2D). In univariate analyses, statistically Docetaxel nmr significant predictors for patient survival were vascular invasion, cell differentiation status, American Joint Committee on Cancer tumor staging, and TCTP expression level (Fig. 2E). In multivariate analyses, TCTP expression level demonstrated better predictive power for patient survival (hazard ratio [HR]: 2.488; 95% CI: 1.020-6.068; P = 0.048, Fig.

2E) than other predictors. Compared to empty vector-transfected QGY-7703 cells (Vec-7703), two TCTP transfectants (TCTP-C2 and TCTP-C7) showed higher expression levels of TCTP (Supporting Fig. 3A). As expected, TCTP-C2 and C7 cells showed higher frequencies of foci formation, when compared to Vec-7703 cells (P < 0.001; Supporting Fig. 3A; Fig. 3B). Vec-7703 and TCTP-7703 cells (the pool of TCTP-C2 and TCTP-C7) were subcutaneously injected into the left and right dorsal flank of each mouse (n = 6), respectively. Tumor formation was observed in 5 of 6 and 1 of 6 of TCTP-7703 and Vec-7703-injected nude mice, respectively (Fig. 3B). The average volume of tumors induced by TCTP-7703 was significantly larger than that induced by Vec-7703 cells (Fig. 3C).

e., they had portal hypertension) and, upon follow-up, HVPG was more predictive of clinical decompensation than histological fibrosis staging. Simple histologic features may also

have important prognostic implications in cirrhotic liver biopsies. For example, the thickness of fibrous septa correlates with HVPG and is an independent predictor of both clinically significant portal hypertension (i.e., HVPG > 10 mmHg)20 and clinical decompensation.21 Moreover, digital image analysis of septal thickness, but not total fibrosis area, predicts cirrhosis decompensation.22 Studies performed in the past two decades have identified several attractive targets for antifibrotic treatment. These include the major cellular sources of scar, most notably activated hepatic stellate cells and find more portal myofibroblasts, as well as key cytokines such as platelet-derived growth factor and transforming growth factor beta.23 The roles of bone marrow–derived cells and those arising from epithelial-mesenchymal Venetoclax chemical structure transition are still under evaluation, but it is unlikely that these sources of fibrogenic cells provide a major contribution to

hepatic extracellular matrix in chronic human liver disease. Cellular sources of proteases that degrade scar and the pathways that regulate them are better understood. Moreover, a more nuanced understanding of distinctive pathogenic features of fibrosis at different stages and from different etiologies means that fibrosis may be customized according to its duration and underlying cause. Cirrhosis in experimental models and human disease may be reversible.24 Following withdrawal of an injurious stimulus, DNA ligase a dense micronodular cirrhosis can undergo remodeling to a more attenuated, macronodular pattern. However, some septa will persist, likely representing those laid down early in the injury and are

therefore the most “mature” (i.e., cross-linked). Moreover, in experimental models, such mature scars may be the site of neoangiogenesis. Such angiogenesis is already present in chronic inflammatory liver diseases25 concurrent with the fibrogenic process and may also play a role in the pathogenesis of portal hypertension.26 The effectiveness of therapeutic angiogenic inhibitors in not only improving fibrosis, but also in reducing portal pressure, is suggested by data from animal models but has not been established in humans.27 Although there are no data linking septal remodeling to portal pressure changes, recent work correlating increased portal hypertension with smaller nodule size and septal thickening suggests that reversal of these events might lower portal pressure.20 These rodent models and human studies throw into relief the inadequacy of a simple one stage classification, because although the micronodular and remodeled attenuated macronodular cirrhosis are very different, they are both defined by the same original pathologic description: “cirrhosis”.

Although PVT carries independent prognostic value for a poorer outcome, it is not a direct cause for aggravation. These data point to PVT and aggravation as discrete consequences of a common determinant for progression of cirrhosis, e. g. hepatic or intestinal microcirculatory dysfunction. Disclosures: Dominique Valla – Board Membership: Sequana Medical; Independent Contractor: IRIS; Speaking and Teaching: Mayoly

Spindler, MSD, Janssen Pharmaceuticals The following people have nothing to disclose: Filipe G. Nery, Cendrine Chaffaut, Bertrand Condat, Emmanuelle de Raucourt, Larbi Boudaoud, Pierre-Emmanuel Rautou, Aurelie Plessier, Dominique Roulot, Jean Claude Trinchet, Sylvie Chevret Background Buparlisib concentration and Aims: The current definitions

for AKI and Hepatorenal syndrome (HRS) have been derived from patients with cirrhosis (CLD). There is paucity of data on AKI in patients with ACLF. We investigated the prevalence, spectrum, natural history and outcome of AKI in patients with ACLF [Asian Pacific Association for Study of Liver, (APASL), definition] and compared it with a cohort of hospitalized patients with cirrhosis. We also compared outcome and response to terlipressin in HRS (International Ascites Club) in both the groups. Methods: AKI was defined according to Acute Kidney Injury Network (AKIN )criteria. Serial creatinine until improvement or upto day 30 was recorded for all patients. Results: Patients with AcLF (n=534) were predominantly Selinexor males (p<0.0001), younger (p<0.0001) with higher serum bilirubin (p<0.0001), INR (p<0.0001), hepatic encephalopathy (p<0.0001), GI bleed (p<0.0001) and mortality (p<0.0001) as compared to CLD (n=2083). AKI

at baseline was significantly more common in patients with ACLF (50.5% vs. 32.3%; p<0.0001) and associated with increased risk of mortality (59.9% vs. 41.3%; p<0.0001) as compared to CLD. A significant difference was also observed in the spectrum of AKI (p<0.0001) with sepsis related AKI as commonest cause in ACLF (160; 58.8%) and prerenal (289; 43%) in CLD. Presence of ACLF (vs CLD) was associated with a six-fold increased risk of AKI (p<0.0001, OR 95% CI 4.9-8.3) on multivariate analysis. There was no significant difference seen in the AKIN stage at baseline (Stage 1 : 61% vs 69%; Stage 2: 29.5% vs 23.5%; Stage 3: 9.9% vs 8.5%), decrease in serum creatinine at FER 48 hours (67.3% vs 65.3%) and in the overall progression of AKI (48.5%vs 45.1%), however, requirement of renal replacement therapy (RRT) and progression to AKIN stage 3 (23.5% vs 12.6%) was significantly more common in ACLF (p<0.0001). Presence of HRS (28.7% vs 29.2%) and response to terlipressin (44.1% vs 44.3%) was not significantly different in both the groups, however HRS in ACLF was characterized by an increased mortality (67.9% vs 45.9%; p=0.001) and progression to acute tubular necrosis (ATN) with higher need of RRT (53.8%vs 20.4%; p<0.

Cysteine oxidation resulted also in structural modifications of the find more diatom RUBISCOs, as recognized by a higher sensitivity of the oxidized enzyme to in vitro proteolysis. The coincident redox properties of red- and green-like RUBISCO types suggest that these changes are part of a physiologically significant regulatory mechanism that has been convergently implemented in both groups with a different set of cysteine

residues. “
“Rapid growth in the biotechnological industry and production has put tremendous pressure on the biological methods that may be used according to the guidelines of green chemistry. However, despite continuing dramatic increases in published research on organic biotransformation by microorganisms, more research exists with microalgae. Our efforts Temozolomide in transforming chemicals such as organic compounds for the production of functionalized products help to lessen the environmental effects of organic synthesis. These biotransformations convert organic contaminants to obtain

carbon or energy for growth or as cosubstrates. This review aims to focus on the potential of microalgae in transformation, conversion, remediation, accumulation, degradation, and synthesis of various organic compounds. However, these technologies have the ability to provide the most efficient and environmentally safe approach for inexpensive biotransforming of a variety of organic contaminants, which are most industrial residues. In addition, the recent advances in microalgal bioactivity PTK6 were discussed. “
“Allelopathic interactions among phytoplankton are well documented. The potency of allelopathic species and responses of target species to allelochemicals are quite variable, however, limiting full understanding of the role these interactions may play in nature. One trait that may influence the sensitivity of an individual to allelochemicals is cell size. The few studies that have examined relationships between cell size and susceptibility

to allelochemicals have compared different species and thus could not distinguish between the role of size and species-specific physiological differences. Culturing an actively sexually reproducing diatom allowed us to focus on the influence of target cell size within a single species. We studied growth and nutrient acquisition by the chain-forming Thalassiosira cf. gravida Clever in the presence and absence of allelochemicals released by Alexandrium fundyense Balech as a function of T. cf. gravida cell size. Upon exposure to filtrate of A. fundyense, T. cf. gravida cultures “bleached” and both growth and nutrient utilization ceased for up to 4 d. The magnitude of the effect was dependent on filtrate concentration and T. cf. gravida cell surface area:volume ratio. The greatest inhibition was observed on the smallest cells, while T. cf.

Cysteine oxidation resulted also in structural modifications of the GSK2126458 diatom RUBISCOs, as recognized by a higher sensitivity of the oxidized enzyme to in vitro proteolysis. The coincident redox properties of red- and green-like RUBISCO types suggest that these changes are part of a physiologically significant regulatory mechanism that has been convergently implemented in both groups with a different set of cysteine

residues. “
“Rapid growth in the biotechnological industry and production has put tremendous pressure on the biological methods that may be used according to the guidelines of green chemistry. However, despite continuing dramatic increases in published research on organic biotransformation by microorganisms, more research exists with microalgae. Our efforts Selleck LY2606368 in transforming chemicals such as organic compounds for the production of functionalized products help to lessen the environmental effects of organic synthesis. These biotransformations convert organic contaminants to obtain

carbon or energy for growth or as cosubstrates. This review aims to focus on the potential of microalgae in transformation, conversion, remediation, accumulation, degradation, and synthesis of various organic compounds. However, these technologies have the ability to provide the most efficient and environmentally safe approach for inexpensive biotransforming of a variety of organic contaminants, which are most industrial residues. In addition, the recent advances in microalgal bioactivity PAK5 were discussed. “
“Allelopathic interactions among phytoplankton are well documented. The potency of allelopathic species and responses of target species to allelochemicals are quite variable, however, limiting full understanding of the role these interactions may play in nature. One trait that may influence the sensitivity of an individual to allelochemicals is cell size. The few studies that have examined relationships between cell size and susceptibility

to allelochemicals have compared different species and thus could not distinguish between the role of size and species-specific physiological differences. Culturing an actively sexually reproducing diatom allowed us to focus on the influence of target cell size within a single species. We studied growth and nutrient acquisition by the chain-forming Thalassiosira cf. gravida Clever in the presence and absence of allelochemicals released by Alexandrium fundyense Balech as a function of T. cf. gravida cell size. Upon exposure to filtrate of A. fundyense, T. cf. gravida cultures “bleached” and both growth and nutrient utilization ceased for up to 4 d. The magnitude of the effect was dependent on filtrate concentration and T. cf. gravida cell surface area:volume ratio. The greatest inhibition was observed on the smallest cells, while T. cf.

08 g/mL in iodixanol gradient (corresponding to 1.18 g/mL in sucrose gradient) and were infectious as indicated by passage to naïve HepaRG cells; (3) HCV E1E2 and core protein accumulation in the cytoplasm of infected cells 1 month p.i.; (4) complete reduction of HCV RNA and infectious virus in HepaRG culture supernatants (97% at 3 weeks

find more p.i.) by E1E2-specific mAb D32.107-9 at low concentration (0.5 μg/mL) even when the infection was performed in the presence of NHS; (5) ability of infected-HepaRG cells to produce high titers of HCV RNA (4 to 5log10) as complete virus particles in culture media after freezing/thawing and subculture(s) followed by induction of the differentiation process; (6) production of apoE/apoB-associated HCV virions by the HepaRG cells similar to authentic patient-derived HCV particles11, 14; (7) observation of typical positive-strand RNA IWR 1 virus-induced membrane rearrangements18 and detection of HCV E1E2 antigen in association with vesicular structures in ER and at a submembranous localization in HCVsp-RG cells. Very recently, a cell-culture-based system was established using PHHs inoculated with HCVcc.16 Even if freshly isolated PHHs are currently the in vitro “gold standard” of human liver

cells, the HepaRG human hepatic cell line is now increasingly used as a surrogate for PHHs in pharmaceutical research and development for metabolism studies.17

Here, our results selleck chemical demonstrate that HepaRG cells can be infected with serum-derived HCV of genotype 3 and persistently produce infectious enveloped HCV particles with biophysical and immunological properties similar to circulating7, 11 and infected liver-derived10 HCV. The major contributions of our study were to use a genuine HCV isolate from patients distinct from the JFH-1 or Jc1 virus of genotype 2a together with the HepaRG cell line, which possesses key features of authentic hepatocytes. Of course, the current Huh-7-derived HCVcc system remains the “gold standard,” and it would have been optimal to successfully infect HepaRG cells with HCVcc. Unfortunately, only a weak transient replication was obtained in our laboratory when we tried to inoculate differentiated HepaRG cells with a highly infectious JFH-1 inoculum (Durantel et al., unpubl. data). This could be due to the production of type-I interferons in the culture medium,18 which likely should inhibit HCV replication and spreading. This could also explain why the HepaRG cells are only susceptible to HCVsp infection when they exhibit dedifferentiated, depolarized epithelial phenotype associated with an immature innate immunity, resistance to apoptosis, and cellular growth.