However, it seems that after induction by viral RNA mimics IFNL4 is merely enriched in the cytosol and it remains to be determined whether the protein is secreted to interact with cell surface receptors. Although intracellular overexpression of the IFNL4 protein appears to induce ISG expression, cells treated with recombinant Y-27632 protein failed to do so at significant levels. These findings indicate that further studies are needed to characterize the functional properties of the identified gene products, their mechanism of action, and their functional relevance in antiviral defense mechanisms. Second, the study may provide

insights into the understanding of the genetic evolution of innate immune responses. The authors found that the ss469415590[δG] frameshift variant encoding the putative IFNL4 is more common in AA patients and correlates with reduced HCV response in large clinical cohorts.18 The authors discussed the possibility that the beneficial allele ss469415590[TT] abrogating IFNL4 may have been selected during geographically

distinct Panobinostat purchase human evolution.18 It is tempting to speculate that the original purpose of the putative IFNL4 may have been important for the innate immune defense against other pathogens. It is conceivable that in an evolutionary context the “loss” of IFNL4 in humans occurred predominantly in geographic regions where the selective pressure from those pathogens eased. Moreover, since predominantly HCV-infected patients with genotype 1 were studied by the authors, a comprehensive multifactorial analysis of ss469415590 involving additional click here HCV genotypes, ethnic background, and geographic prevalence of different HCV genotypes may provide interesting insight into HCV evolution. For example, it will be interesting to determine whether more difficult-to-treat genotype 1 viruses co-evolved together with the selection of the ss469415590[TT].

Finally, the findings of the study may have clinical relevance for the management of patients with CHC. The recent groundbreaking discovery that SNPs in the region of IFNL3 are predictors for treatment outcome of CHC had revealed a new perspective for customized IFN-based therapies.8–16 In this context, potential algorithms have been proposed to utilize IFNL3 genotyping in the initial treatment decision making for CHC infections.19 Prokunina-Olsson et al. now extend these findings by revealing that ss469415590[δG] is more strongly associated with HCV clearance in AAs than the previously described SNPs, although it provides comparable information in patients with European and Asian ancestry.18 Including the upstream ss469415590 in the IFNL3 genotyping in the treatment decision algorithm may increase the reliability of prediction of IFN-based treatment outcome, especially in patients with African ancestry.

In subsequent years the patient was admitted several times for hepatic encephalopathy. In June 2011 a routine ultrasound showed a new 1-cm hypoechoic

mass in the dome of the liver which was indeterminate on contrast CT scan. The alphafetoprotein level was 117.5 ng/mL. The lesion grew to 1.9 × 1.4 × selleck kinase inhibitor 1.7 cm in March 2012 on ultrasonography. On contrast CT the lesion was hypervascular but indeterminate, as it measured less than 1 cm (Fig. 1A,B). The AFP was 107.6 ng/mL in October 2011 but was 4.3 ng/mL in May 2012 (Fig. 1C). Due to the increasing size of the lesion an ultrasound-guided biopsy of the liver mass was performed in April 2012 and reviewed by three pathologists who concurred that there was evidence of well-differentiated HCC on a background of HCV cirrhosis (Fig. 2). The patient was GSK458 nmr scheduled for radiofrequency ablation (RFA) therapy and relisted for LT, but

died from complications of liver failure while waiting. HCV accounts for nearly half of all LT done in the U.S. and Europe.[1] Unfortunately, viremia persists in over 95% of patients posttransplant and cirrhosis can occur within 5 years of HCV recurrence in transplant patients,[2, 3] resulting in liver failure and death. HCV is a well-established risk factor for HCC in patients with cirrhosis, but to our knowledge no case has been reported of a patient with recurrent HCV developing HCC posttransplant. The rapid development of HCC in our patient selleck products was likely multifactorial and related to the development of recurrent HCV. Immunosuppression affects the natural history of recurrent HCV and accelerates the development of cirrhosis.[2] Mechanistically, CD8 T cells are responsible for lysis of tumor and virus-infected cells by way of antigen presentation with up-regulation of cytokines by CD4 T cells.[4] Thus, the T-cell response to HCV is critical in achieving long-term control of the virus and prolonging the time

between viremia and the presence of tumor.[5] Immunosuppressive medications decrease immune-mediated viral elimination and suppress the immune tumor surveillance system. Consequently, transplant recipients have a 2-4 times greater risk of de novo malignancy compared to transplant-naïve patients.[6] Specifically, posttransplant immunosuppression may also promote tumorigenesis. Tacrolimus has been shown to accelerate the doubling time for recurrent HCC from 273 to 37 days[7] and may have accelerated the doubling time of this patient’s cancer. The role of surveillance for HCC is still unclear. AFP levels may be elevated in patients with HCV and this may account for the discordance seen in our patient (Fig. 1D). In conclusion, cirrhosis from recurrent HCV after OLT can be associated with de novo HCC. The incidence and role of surveillance have yet to be defined and need further study.

Noteworthy, enrichment of miR-492-suppressed genes was most significantly overrepresented in functional clusters assorted by metal binding properties, by extracellular space occurrence, or by the more general category of developmental processes. They include, e.g., members of the copper and cadmium binding MT1 (metallothionein) gene family, which is instrumental to regulate aggressive neoplastic cell growth, prognosis, and/or resistance against radiation and chemotherapy Doxorubicin in vivo in a variety of human neoplasias,

including HCC.34, 35 Moreover, the members of the ALB/AFP/AFM (albumin, alpha fetoprotein, afamin) multigene family were found, which belong to the earliest genes to be expressed in the fetal liver in mammals.36 Despite the limitations in transferring findings on regulatory circuits defined in HB cell culture to the HB tumor biology, it is tempting to speculate that KRT19-associated miR-492 overexpression could act as a regulatory component to counteract some gene expressions (e.g., MT1 or AFP) that might

otherwise drive the tumor toward an unfavorable phenotype. Within this set of suppressed genes we identified putative direct targets of miR-492 by using target prediction algorithms and quantitative PCR-based verification. They included BAAT, ST6GAL1, TCF21, HSD3B1, ALB, BID, GDA, and CDKN2A. Consistently, an inverse relationship to miR-492 expression was noted selleck screening library in HB tumors for most of these candidate targets. selleck compound However, the level of significance was reached only for BAAT, which might be due to the heterogeneous composition of tumor tissue. Because BAAT, ST6GAL1, ALB, and GDA are mainly expressed in the mature liver, these data suggest that high miR-492 levels in HB might indicate a rather immature stage of the tumor. Because miR-492 closely correlates with KRT19 expression and obviously influences genes involved in tumor progression and hepatocyte differentiation, we wondered whether this might be reflected in the clinicopathological features of HB. Indeed,

both markers were significantly higher expressed in metastatic stages compared to nonmetastatic stages, although only a small cohort of 26 HB tumor samples was available for this study. This observation would be consistent with data published by Cairo et al.18 demonstrating that HB tumors with high expression of KRT19 are attributed as a poor prognostic group. Metastasis-related miRNAs have also been discovered in HCC.24 MiR-492, however, did not show up as significantly out-regulated in HCC miRNA profiles.24, 25 Equally, a recently published list of miRNAs being potentially involved in HB genesis37 does not contain miR-492. This might be due to the relatively weak expression level of miR-492, which could result in a loss of this candidate by background corrections of miRNA arrays.

Patients should avoid activities likely to cause trauma (see ‘Fitness and Physical Activity’). Regular monitoring of health status and assessment of outcomes are key components of care (see ‘Monitoring Health Status and Outcome’). Drugs that affect platelet function, particularly acetylsalicylic acid (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs), except certain COX-2 inhibitors, should be avoided. Paracetamol/acetaminophen is a safe alternative for analgesia (see ‘Pain Management’). Factor levels should be raised to appropriate levels prior to any invasive procedure (see ‘Surgery and Invasive Procedures’). Good oral hygiene is essential

to prevent periodontal disease and dental caries, which predispose to gum bleeding (see ‘Dental Care and Management’). Comprehensive care promotes physical and Selleck Seliciclib psychosocial health and quality of life while decreasing morbidity and mortality. (Level 3) [ [7-9] ] Hemophilia is a rare disorder that is complex to diagnose and to manage. Optimal care of these patients, especially those with severe forms of the disease, requires more than the treatment of acute bleeding. Priorities in the improvement

of health and quality of life of people with hemophilia include: prevention of bleeding and joint damage prompt management of bleeding management of complications including: ○ joint and muscle damage and other sequelae see more of bleeding The wide ranging needs of people with hemophilia and their families are best met through the coordinated delivery of comprehensive care selleck products by a multidisciplinary team of healthcare professionals, in accordance with accepted protocols that are practical and national treatment guidelines, if available. (Level 5) [ [10-12] ] The comprehensive care team should be multidisciplinary in nature, with expertise and experience to attend to the physical and psychosocial

health of patients and their families. The core team should consist of the following members: a medical director (preferably a pediatric and/or adult hematologist, or a physician with interest and expertise in hemostasis) a nurse coordinator who: ○ coordinates the provision of care To provide or coordinate inpatient (i.e., during hospital stays) and outpatient (clinic and other visits) care and services to patients and their family. Patients should be seen by all core team members at least yearly (children every 6 months) for a complete hematologic, musculoskeletal, and psychosocial assessment and to develop, audit, and refine an individual’s comprehensive management plan. Referrals for other services can also be given during these visits. (Level 5) [ [13, 14] ] The management plan should be developed with the patient and communicated to all treaters and care facilities. Communication among treaters is important.

Results: (1) In all types of FBs, food which included

food lump, fish bone, chicken bone shrimp, crab and fruit seeds accounted for 92.9% and 81.1% in rigid and flexible endoscopy group respectively. The size of FBs in flexible group was larger than rigid group (P < 0.05). (2) The proportions of FBs impacted in upper esophagus was higher in rigid group (88.7%) than flexible group (60.8%), but lower in inferior esophagus. (3) The period impacted in esophagus of rigid group (26.2 ± 28.3 hrs) was longer than flexible group (14.4 ± 13.0 hrs)(P = 0.001). (4) 69.7% patients in rigid group and 86.5% in flexible group went to hospital for treatment within 24 hours from impacted. 13.4% in rigid and 1.4% in flexible group went to hospital beyond 48 hours. (5) The proportion of FBs puncturing into one or two esophageal wall Ferroptosis phosphorylation in rigid group (69%) was higher than flexible Torin 1 cost group (31.1%). (6) Positive rate with upper gastrointestinal barium contrast and chest X-ray or abdominal plain film were 98.5%, 23.9% and 94.4%, 22.7% for diagnosing esophageal FBs in rigid and flexible group. (7) The successful rate, complication and perforation rate were 100%, 65.1%, 5.6%

and 97.3%, 47.3%, 1.4% in rigid and flexible endoscopy group, respectively. Conclusion: There was no difference in complication and perforation rate between rigid and flexible endoscopy. The successful rates were both high with two treatment, but flexible endoscopy was more cheaper and no need to aneasthesia. Key Word(s): 1. Esophageal FBs; 2. Foreign body; 3. Endoscopy; 4. Management; Presenting Author: LI SHU Additional Authors: LIN RUI, ZHOU LU, WANG BANGMAO Corresponding Author: LI SHU Affiliations: Tianjin Medical University General Hospital; No. 154, Anshan Road, Heping District, Tianjin Objective: The goal of this study was to investigate the clinical value of narrow-band imaging endoscopy (NBI) and magnification chromoendoscopy (MCE) in diagnosis

of early gastric cancer (EGC) and precancerous lesions. Methods: One hundred and fourteen patients with selleck screening library 137 gastric lesions were enrolled. Routine endoscopy followed by NBI, magnification chromoendoscopy (indigo carmine, IC) was sequentially used. The quality of the gastric lesions, pits and microvascularity were evaluated. The gastric pits and microvascularity were observed and divided into corresponding patterns. The biopsy samples were taken in suspicious area. The values in diagnosis of EGC and precancerous of NBI and MCE were compared. Results: (1)  Visualization of silhouette of gastric lesions by NBI endoscopy and chromoendoscopy were clearer than the conventional endoscopy. There was no significant difference between MCE + NBI and chromoendoscopy MCE + IC. Gastric pit by NBI combined with ME was clearer than MCE and ME. Gastric mucosa microvascularity by NBI combined with ME was clearer than the ME and indigo carmine MCE.

Inhibitor activity of patient samples is read in NBU mL−1 from a semi logarithmic plot representing the correlation between residual FVIII activity (logarithmic) and inhibitor activity (linear) [15]. The regression line is fully defined by 100% residual FVIII activity with 0 NBU mL−1 inhibitor and 50% residual FVIII activity with 1 NBU mL−1 inhibitor (Fig. 2). Dose–response curves of test plasma need to show parallelism with this calibration curve. If not, inhibitor data are not reliable and an alternative

strategy needs to be followed (e.g. type II FVIII inhibitors). When the residual FVIII activity of undiluted sample is below 25%, retesting of more diluted samples is recommended because of non-linearity of inhibitor concentration and residual FVIII activity with high inhibitor titres. Dilutions selleck compound have to be made with FVIII-deficient plasma. The internationally accepted cut-off value for Bethesda-based inhibitor assays is 0.6 BU mL−1. This value is rather

high, for it has been derived from the results with the classical Bethesda assay and is a reflection of the low sensitivity buy PD0325901 and specificity of this method. However, sensitivity and specificity, including the cut-off value, have been improved in the Nijmegen assay [14] although clinical studies comparing inhibitor titres and kinetic parameters are still lacking. Therefore, every individual laboratory has to assign the laboratory-specific cut-off value by assaying positive and negative inhibitor samples from haemophilia patients. The FVIII inhibitor assay is rather complicated and includes critical analytical stages and variables that need careful handling to get reliable results. The inactivation of FVIII by inhibitors is pH-, temperature- and time-dependent. The

pH stability of the incubation mixtures is an essential feature of the Nijmegen assay. Incubation of insufficiently buffered plasma mixtures will give rise to increasing pH resulting in uncontrolled and non-specific inactivation of FVIII [13,16]. pH stabilization of learn more the incubation mixture by buffering the normal pooled plasma will overcome this problem and will increase the specificity and sensitivity of the method. The effect of incubation time and temperature on the measured inhibitor titre is shown in Fig. 3a,b. The experiments were performed using a purified inhibitor directed towards A2 and C2 domain [17] diluted in FVIII-deficient plasma. At 37°C, an optimal inhibitor titre is reached after 120 min of incubation (Fig. 3a). At incubation times more than 180 min, a marked decrease of FVIII activity is noticed even in the control sample (Fig. 3b) rendering the inhibitor data unreliable at longer incubation times. In contrast, at room temperature the FVIII activity in the control mixture remains stable up to 240 min (Fig. 3b) whereas, in the test mixture, the remaining FVIII activity does not reach a stable level in this period because of slow-acting progressive inhibitor activity.

A comparison of 29 commercial serological kits (17 ELISAs and 12 ICTs) was carried out in France.

Depending on the type of analysis performed, 2 to 4 of the ELISAs presented an excellent performance. In contrast, only one of the 12 ICTs had an accuracy >90% [32]. A line assay using 6 recombinant proteins corresponding to virulence factors (CagA, VacA, GroEL, gGT, HcpC, and UreA) was developed in Germany. It was validated on a group of 600 patients (42% H. pylori positive by histology) and showed 97.6% sensitivity and 96.2% specificity, that is, an improvement on currently available serological tests [33]. The same group in collaboration with researchers in Iran was able to identify a H. pylori protein, FliD, essential in the BTK inhibitor concentration assembly of the flagella. The recombinant FliD protein was tested on a group of 618 patients (51.4% H. pylori positive) with 97.4% sensitivity and 99% specificity using a line assay, and 97 and 96% by ELISA, respectively [34]. Other attempts to select antigenic proteins of potential diagnostic value were made (CafI, ureG, ureB), but have not been evaluated yet [35]. Interestingly, using

Helicoblot 2.1 (Genelabs Diagnostics, Singapore), it was possible to identify a low molecular weight protein (35KDa) associated with a low risk of GC (OR = 0.4, 95% CI:0.1–0.9) and the VacA protein associated with a high risk of GC (OR = 2.7, 95 CI:1–7.1) among patients with GC (102) and dyspepsia (122) in Iran [36]. A review on ICTs was also produced last year [37]. Pepsinogen JQ1 research buy I and II and their ratio as predictors of atrophy were evaluated this year in Iran [38], Turkey [39], and Italy [40], but they were found to be insensitive predictors of these selleck products lesions. A toll-like receptor 4 was found helpful to differentiate between dysplasia and other precancerous lesions [39]. Both miR-106b and miR-21 were found as markers of increased risk for GC after H. pylori eradication [41]. The progress in imaging techniques allows now to have a more accurate approach of

the features associated to H. pylori infection. There are continuous attempts to improve the existing diagnostic methods or to evaluate their use in real life. Competing interest: The authors have no competing interests. “
“Background:  A remarkable variety of restriction-modification (R-M) systems is found in Helicobacter pylori. Since they encompass a large portion of the strain-specific H. pylori genes and therefore contribute to genetic variability, they are suggested to have an impact on disease outcome. Type I R-M systems comprise three different subunits and are the most complex of the three types of R-M systems. Aims:  We investigated the genetic diversity and distribution of type I R-M systems in clinical isolates of H. pylori. Material and methods:  Sixty-one H. pylori isolates from a Swedish hospital based case-control study and 6 H.

0% in the control group. Xiang et al. described a similar trend in subjects affected by Crohn’s disease, who were positive at biopsy in 27.1% of cases, much less than in the control group (47.9%), with Sunitinib manufacturer no particular difference in the extension of the disease [32]. Looking more closely, the prevalence of this infection appears to have declined over the last decade. Indeed Triantafillidis et al. estimated the prevalence of this infection at 35.5% in 2002, and 24% in 2012 in the IBD group [33]. Finally, Hansen et al. [34] investigated microaerophilic microbiota in the colon of a pediatric population affected by IBD at the onset, showing that Campylobacter appears to be surprisingly common (around

8% of pediatric colonic biopsies), while Helicobacter species are relatively rare. It has been hypothesized that H. pylori could exert an immunomodulatory action on the intestinal mucosa [35], thus protecting against IBD but, at the moment, there is only a speculative observation that H. pylori infection has a relative risk for IBD of 0.43–0.59 [36]. Therefore, in the absence of strong evidence, the most reasonable see more explanation is that this trend could be attributed to previous antibiotic treatments, very frequent in subjects suffering from IBD [33]. It is a debated topic whether H. pylori might induce direct damage on the intestinal mucosa. Kim et al. reported multiple small bowel ulcerative lesions associated with H. pylori in an 11-year-old girl without any

systemic disease [37]. Authors justified this event due to a weak mucosal defense mechanism against the bacterium for a structural deformity of the duodenal bulb caused by a previous gastrotomy. Even though a clear relationship

could not be found, basic research demonstrated that H. pylori can use its pathogenic action against colonic cells, when they produce a gastric mucin (MUC5AC) [38]. Finally, secretory antibodies can modulate the progress of H. pylori infection, particularly in the duodenum, as shown by Gorrell et al.: Knockout mice for polymeric immunoglobulin receptors had a very intense colonization of the duodenum [39]. Competing interests: The authors have no competing interests. “
“Background: Helicobacter pylori infection has been proved to be of great relevance to public health in unindustrialized countries, especially in low socioeconomic groups. Poor selleck compound hygiene, deficient sanitation, and crowded conditions have been reported as risk factors for this infection. In this work, we investigated whether social and demographic characteristics were associated with anti-H. pylori IgG antibodies in 1104 children aged 4–11 years old from Salvador, a large city located in northeastern Brazil. Methods:  Standardized questionnaires were used to obtain social, demographic, and environmental data for the studied population in two periods of time (from 1997 to 2003 and in 2005). Anti-H. pylori IgG antibodies were assessed by indirect enzyme-linked immunosorbent assay in 2005. Results:  Anti-H.

The analysis was conducted using a fixed-effects or random-effects model. Results: Twenty studies meeting the inclusion criteria were included in this meta-analysis. No significant heterogeneity was found across them. It was shown that higher level or positive ATIs is a significant predictor for loss of Infliximab treatment response (OR = 0.22, 95%CI = 0.09–0.54), and which is a slight but not significant predictor Protein Tyrosine Kinase inhibitor for clinical remission (OR = 0.71, 95%CI = 0.35–1.43). In addition, closely connection was found between ATIs development and treatment strategies (OR = 3.38, 95%CI = 1.42–8.05), concomitant immunosuppressant (OR = 0.38,

95%CI = 0.29–0.48). Presence of ATIs often accompanied with higher risk of infusion reaction (OR = 2.35, 95%CI = 1.60–3.45). Conclusion: This meta-analysis indicated that higher level or positive of ATIs predicts loss of response to infliximab and a higher rate of infusion reaction. Meanwhile scheduled Infliximab click here treatment and immunomodulator administering concomitantly, can be taken to reduce ATIs formation. Key Word(s): 1. Infliximab; 2. ATIs; 3. IBD; 4. meta-analysis; Presenting Author: HUI WU Additional

Authors: XIAOLAN ZHANG Corresponding Author: XIAOLAN ZHANG Affiliations: The Second Hospital of Hebei Medical University Objective: The aberrant immunological selleck chemical reaction is considered an important cause of ulcerative colitis (UC), especially the imbalance of T helper (Th)1 and Th17.1,25-dihydroxyvitamin D3 (1,25 (OH)2D3) was proved an primary regulator of the immune system. The study investigated the influence of 1,25 (OH)2D3 in the spleen immune, the most important peripheral immune organ, by the chronic experimental colitis mice induced by dextran sodium sulfate (DSS). Methods: There are three groups in the study: Control group (receive distilled water), DSS and DSS+VD group (received DSS water). The DSS+VD group received 1,25 (OH)2D3 from the 14th day. Severity

of the disease was assessed by body weight (BW), disease activity index (DAI), splenic morphology, weight, length, the spleen index (SI) and histopathology. The levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin (IL)-17 and IL-6 were also detected. Results: BW was significantly decreased in the DSS group than that in the Control group, and restored rapidly in the DSS+VD group. The DSS group developed higher DAI, splenomegaly, the spleen weight, length and the SI were remarkably increased than that in the Control group, while lessened in the DSS+VD group than that in the DSS group. The number of mononuclearcells, also the percentage of the macrophages and the dentritic cells in the DSS group were significantly increased, and decreased in the DSS+VD group.

Such analysis using serum has clarified the metabolic alteration in various liver diseases, Palbociclib solubility dmso such as viral hepatitis,14 acetaminophen-induced liver toxicity,15 and cholestatic liver disease16. Thus, the intriguing possibility has emerged that serum metabolomic analysis enables the discovery of endogenous metabolites that are significantly altered in NASH. In the present study, to explore endogenous metabolites associated with NASH, a comprehensive analysis of serum metabolites was carried out using UPLC-ESI-QTOFMS in mice treated with a methionine- and choline-deficient (MCD) diet, a representative

mouse model of NASH, and gene expression patterns were assessed to understand the mechanism of serum metabolite changes. Abcb, ATP-binding cassette subfamily B member; Abcc, ATP-binding cassette subfamily C member; Alox12, arachidonate 12-lipoxygenase; ALP, alkaline KPT-330 price phosphatase; ALT, alanine aminotransferase; CD, choline-deficient; Cyp, cytochrome P450; Enpp2, ectonucleotide pyrophosphatase/phosphodiesterase

2; ER, endoplasmic reticulum; GalN, D-galactosamine; HETE, hydroxyeicosatetraenoic acid; IL, interleukin; LPC, lysophosphatidylcholine; Lpcat, lysophosphatidylcholine acyltransferase; LPS, lipopolysaccharide; Lypla1, lysophospholipase A1; MCD, methionine- and choline-deficient; MCS, methionine- and choline-supplemented; MD, methionine-deficient; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NOX, NADPH oxidase; OPLS, orthogonal projection to latent structures; PC, phosphatidylcholine; PCA, principal components analysis; Ostb, organic solute transporter β; qPCR, quantitative polymerase chain reaction; Slc10a1, solute carrier family 10 member 1; Slco, solute carrier organic anion transporter family member; SS, simple steatosis; TG, triglycerides; TGF, transforming growth factor; TNF, tumor necrosis factor; UPLC-ESI-QTOFMS, ultraperformance liquid chromatography–electrospray ionization–quadrupole time-of-flight mass spectrometry. All animal studies were conducted in accordance with Institute of Laboratory Animal Resource

(ILAR) guidelines and were approved by the National Cancer Institute Animal Care and Use Committee. The mice were housed in a specific pathogen-free environment controlled check details for temperature and light (25°C, 12-hour light/dark cycle) and maintained with NIH31 regular chow and tap water ad libitum. For MCD diet-induced NASH, male C57BL/6NCr mice at 8-10 weeks of age were used. The MCD diet was purchased from Dyets Inc. (#518810; Bethlehem, PA), and a methionine- and choline-supplemented MCD diet (MCS, #518754; Dyets) was used as a control diet. Five days before starting the experiments, NIH31 chow was replaced with the MCS diet for acclimatization. The study of MCD diet–induced NASH consisted of three independent experiments.