5% experienced single adefovir, 12.0% experienced single lamivudine, 49.4% experienced both adefovir and lamivudine, and 15.8% experienced adefovir/lamivudine plus telbivudine/entecavir). Only four patients with rtA181T were antivirals-naive. HBV genotype C/B were 93.0%/7.0% for rtA181T positive patients, and 84.6%/15.4%

for rtA181T negative patients (P <0.01), suggesting there was a positive link between rtA181T with genotype C HBV. Most but not all rtA181T led to sW172* (stop codon) mutation on overlapping S-gene and coexistence of rtA181T/sW172* with wild-type sequence was frequently detected (22.0% presented as sW172* alone, 69.9% presented GDC-0449 research buy as sW172* concomitant with the wild-type, 5.7% presented as sW1 72* with sW1 72/L or sW172S, etc). Phenotypic analysis of representative rtA181T/sW172* strains showed that the 50% effective concentration (EC50) values of adefovir for the mutants were 1.8-fold to 2.9-fold higher than that of wild-type strain. By contrast, the EC50 of adefovir for rtA1 81V or rtN236T mutants was at least 3.5-fold higher than that of wild-type strain. A defect in HBsAg secretion and a decreased replication capacity of rtA181T Selleckchem GPCR Compound Library (sW172*) strain were observed in comparison with wild-type strain in vitro; while no significant difference in average serum HBsAg and HBV DNA levels was observed between patients with and without rtA181T/sW172*. Conclusions: The emergence of HBV rtA181T mutation is closely

associated with adefovir and lamivudine exposure, but it may not directly cause adefovir resistance. The clinical significance of rtA181T should be properly interpreted. Disclosures: The following people have nothing to disclose: Xiaodong Li, Yan Liu, Liming Liu, Pan Zhao, Jiuzeng Dai, Zengtao Yao, Shaojie Xin, Dongping Xu Introduction: in chronic Hepatitis B (CHB), loss of hepatitis B surface antigen (HBsAg) and seroconversion to anti-HBs is generally considered as the ultimate goal of antiviral therapy. New combination therapy of Pegylated

interferon (PegIFN) with potent HBV Inhibitors such as tenofovir (TDF) is assessed in order to Cyclin-dependent kinase 3 improve the rate of HBsAg loss. The HBsAg gene contains the “a determinant” epitope located within the major hydrophilic region (MHR). In this study we investigate the S-gene variability of patients at baseline of PegIFN plus TDF combination therapy in order to determine the role of HBsAg variants on response to treatment. Methods: CHB patients received 180 μg of Peg-IFN/week plus 300 mg of TDF /day during 48 week. Patients were seen every 3 months. Sustained virologic response (SVR) was defined as HBV DNA< 2000UI/mL 48 weeks after end of therapy. Non-sustained virologic response (N-SVR) was defined as HBV DNA > 2000 UI/mL 48 weeks after end of therapy. HBs Ag-encoding gene from each patient’s serum at baseline was PCR-amplified, cloned and sequenced. At mean of 17 clones per patient were analysed. Results: Forty CHB patients were included in this study.

5% experienced single adefovir, 12.0% experienced single lamivudine, 49.4% experienced both adefovir and lamivudine, and 15.8% experienced adefovir/lamivudine plus telbivudine/entecavir). Only four patients with rtA181T were antivirals-naive. HBV genotype C/B were 93.0%/7.0% for rtA181T positive patients, and 84.6%/15.4%

for rtA181T negative patients (P <0.01), suggesting there was a positive link between rtA181T with genotype C HBV. Most but not all rtA181T led to sW172* (stop codon) mutation on overlapping S-gene and coexistence of rtA181T/sW172* with wild-type sequence was frequently detected (22.0% presented as sW172* alone, 69.9% presented AZD2014 ic50 as sW172* concomitant with the wild-type, 5.7% presented as sW1 72* with sW1 72/L or sW172S, etc). Phenotypic analysis of representative rtA181T/sW172* strains showed that the 50% effective concentration (EC50) values of adefovir for the mutants were 1.8-fold to 2.9-fold higher than that of wild-type strain. By contrast, the EC50 of adefovir for rtA1 81V or rtN236T mutants was at least 3.5-fold higher than that of wild-type strain. A defect in HBsAg secretion and a decreased replication capacity of rtA181T PLX4032 chemical structure (sW172*) strain were observed in comparison with wild-type strain in vitro; while no significant difference in average serum HBsAg and HBV DNA levels was observed between patients with and without rtA181T/sW172*. Conclusions: The emergence of HBV rtA181T mutation is closely

associated with adefovir and lamivudine exposure, but it may not directly cause adefovir resistance. The clinical significance of rtA181T should be properly interpreted. Disclosures: The following people have nothing to disclose: Xiaodong Li, Yan Liu, Liming Liu, Pan Zhao, Jiuzeng Dai, Zengtao Yao, Shaojie Xin, Dongping Xu Introduction: in chronic Hepatitis B (CHB), loss of hepatitis B surface antigen (HBsAg) and seroconversion to anti-HBs is generally considered as the ultimate goal of antiviral therapy. New combination therapy of Pegylated

interferon (PegIFN) with potent HBV Inhibitors such as tenofovir (TDF) is assessed in order to Rolziracetam improve the rate of HBsAg loss. The HBsAg gene contains the “a determinant” epitope located within the major hydrophilic region (MHR). In this study we investigate the S-gene variability of patients at baseline of PegIFN plus TDF combination therapy in order to determine the role of HBsAg variants on response to treatment. Methods: CHB patients received 180 μg of Peg-IFN/week plus 300 mg of TDF /day during 48 week. Patients were seen every 3 months. Sustained virologic response (SVR) was defined as HBV DNA< 2000UI/mL 48 weeks after end of therapy. Non-sustained virologic response (N-SVR) was defined as HBV DNA > 2000 UI/mL 48 weeks after end of therapy. HBs Ag-encoding gene from each patient’s serum at baseline was PCR-amplified, cloned and sequenced. At mean of 17 clones per patient were analysed. Results: Forty CHB patients were included in this study.

Ltd., Science & Technology Systems Inc., Bruker Daltonics K. K., for their kind cooperation during this study. “
“Although I am not aged by current criteria, in my formative years as a junior investigator, I remember long hours in the library searching for references. There was no PubMed; instead, a book called IndexMedicus was RG7204 price searched for topics relevant to a field of research, or an information expert in the library was asked to perform a computerized search for a fee. Once articles of interest were identified, they were copied in the library

(often at a cost of $0.05/page). Copy machines were crucial for obtaining the articles. Book binding often precluded laying the book flat and interfered with accurate copying near the seam of the binding. Articles were then read, further references were identified, and this prompted additional trips to the library and p38 MAP Kinase pathway repetitive use of the copying machine. Obtaining and managing references for grants and articles was costly, tiresome, and exasperating. Relevant articles were so difficult to identify and retrieve that senior investigators could often play one-upmanship by quoting pertinent publications of which others were simply unaware. Currently, we can receive an electronic

table of contents, download articles as PDF files, and print or read them on our computer monitor; alternatively, we can run computer searches on PubMed, locate the relevant article, and download the PDF file. Considerable information is now readily available in a real-time, efficient manner. Because of the increasing number of journals and articles, the current

challenge is focusing and managing the search process. However, for access to many recent articles, an individual or institutional subscription to the journal is needed. This fact still poses a barrier to obtaining critical information. Indeed, I am currently writing a grant (still a painful, time-intensive experience), and several articles that I needed to review for emerging and evolving concepts were not available because neither I nor the institution had a subscription. This experience was frustrating and emphasized that barriers between the consumer and scientific information still exist. This problem was meant to be solved by the development of a process for open access to scientific information Carnitine palmitoyltransferase II (the availability of articles online without fees or subscriptions), but obviously universal open access has yet to be obtained. The driving force for open access has been the World Wide Web, which has facilitated a shift from print-only journals to parallel print and electronic formats. Two types of open access now exist: an article can be published in a truly open access journal such as a Public Library of Science (PLoS) journal1, 2 or in a closed access journal with subsequent deposition by the author in an open access forum such as PubMed Central. Often, this second scenario results in delayed open access.

Ltd., Science & Technology Systems Inc., Bruker Daltonics K. K., for their kind cooperation during this study. “
“Although I am not aged by current criteria, in my formative years as a junior investigator, I remember long hours in the library searching for references. There was no PubMed; instead, a book called IndexMedicus was see more searched for topics relevant to a field of research, or an information expert in the library was asked to perform a computerized search for a fee. Once articles of interest were identified, they were copied in the library

(often at a cost of $0.05/page). Copy machines were crucial for obtaining the articles. Book binding often precluded laying the book flat and interfered with accurate copying near the seam of the binding. Articles were then read, further references were identified, and this prompted additional trips to the library and JNK inhibitor chemical structure repetitive use of the copying machine. Obtaining and managing references for grants and articles was costly, tiresome, and exasperating. Relevant articles were so difficult to identify and retrieve that senior investigators could often play one-upmanship by quoting pertinent publications of which others were simply unaware. Currently, we can receive an electronic

table of contents, download articles as PDF files, and print or read them on our computer monitor; alternatively, we can run computer searches on PubMed, locate the relevant article, and download the PDF file. Considerable information is now readily available in a real-time, efficient manner. Because of the increasing number of journals and articles, the current

challenge is focusing and managing the search process. However, for access to many recent articles, an individual or institutional subscription to the journal is needed. This fact still poses a barrier to obtaining critical information. Indeed, I am currently writing a grant (still a painful, time-intensive experience), and several articles that I needed to review for emerging and evolving concepts were not available because neither I nor the institution had a subscription. This experience was frustrating and emphasized that barriers between the consumer and scientific information still exist. This problem was meant to be solved by the development of a process for open access to scientific information Liothyronine Sodium (the availability of articles online without fees or subscriptions), but obviously universal open access has yet to be obtained. The driving force for open access has been the World Wide Web, which has facilitated a shift from print-only journals to parallel print and electronic formats. Two types of open access now exist: an article can be published in a truly open access journal such as a Public Library of Science (PLoS) journal1, 2 or in a closed access journal with subsequent deposition by the author in an open access forum such as PubMed Central. Often, this second scenario results in delayed open access.

7G). Unfortunately, by 6 hours a majority of Lys-Cre Ron TKfl/fl mice were moribund or dead and adequate blood could not be collected for ALT analysis. Importantly, however, at 6 hours ALT levels in Ron TKfl/fl control plasma were significantly higher than Alb-Cre Ron TKfl/fl plasma, suggesting protection of the TK−/− hepatocytes. TUNEL staining was PD-1 antibody inhibitor performed on liver sections at 5 hours to assess the level of apoptosis (Fig. 7D-F). Alb-Cre Ron TKfl/fl liver had statistically lower levels of TUNEL-positive cells followed by control Ron TKfl/fl and Lys-Cre Ron TKfl/fl livers (Fig. 7H). This result is consistent with western analyses for active (cleaved) caspase-3 observed

in liver lysates with the lowest levels of active caspase-3 detected in the Alb-Cre Ron TKfl/fl livers (Supporting Information Fig. S2). To test for survival differences, mice from each group were allowed to proceed until death Buparlisib mw from ALF. Kaplan-Meier survival curves (Fig. 8A) clearly show that Lys-Cre Ron TKfl/fl mice have a significantly shorter survival time. The mean survival time of each genotype is depicted

in Fig. 8B. Although Fig. 7 demonstrates protection from hepatocyte apoptosis and liver injury in the Alb-Cre Ron TKfl/fl mice compared to the other genotypes, overt survival of the Alb-Cre Ron TKfl/fl mice was longer than the Ron TKfl/fl mice but was not statistically different (P = 0.07). Here we dissected the role of Ron receptor TK in an endotoxin-induced model of acute liver failure to further studies

demonstrating that mice with a global deletion of Ron TK had a protected liver injury phenotype.16 Examination of hepatocytes and Kupffer cells showed expression of Ron in both, and importantly, ex vivo experiments showed Ron signaling is critical for both suppressing hepatotoxic Kupffer cell cytokine production and for sensitizing hepatocytes to Kupffer cell-derived products such as TNF-α. Together with in vivo experiments using mice with either hepatocyte- or Kupffer cell-specific deletion of Ron TK, we determined STK38 that Ron TK signaling in both cell types has important effects on hepatocyte survival following exposure to endotoxin in this model of acute liver failure. However, the cell type likely responsible for Ron-dependent hepatic protection in this liver injury model is the hepatocyte, given that lack of Ron signaling in hepatocytes ex vivo and in vivo is sufficient to afford a hepatocyte survival benefit. Following stimulation with LPS, TK−/− Kupffer cells have altered cytokine production ex vivo compared to TK+/+ Kupffer cells, with the most significantly elevated cytokines being IL-1ra (2.5-fold), IL-6 (2-fold), TIMP-1 (1.5-fold), MCP-1 (3.5-fold), and MIP-2 (1.9-fold). A potential mechanism for these perturbations is increased NF-κB signaling in the Ron-deficient state.

Despite their striking diversity, the songs of rattling cisticolas have traits that are a characteristic of the species across a wide geographic range. Song form has likely evolved as a result of multiple evolutionary pressures, including stabilizing selection on some elements for species identification and selection for diversity on the form and frequency characteristics of other elements. In a previous study (Benedict & Bowie, 2009), we found that a congener, the red-faced cisticola, also showed diverse song forms with some species-specific elements, supporting Daporinad the idea that song form is generated by multiple evolutionary pressures (Seddon, 2005). In both cisticola

species, song structure and a few characteristic syllable forms are fixed, but birds of the two species generate song diversity differently. Red-faced cisticolas mix up the ordering Tyrosine Kinase Inhibitor Library of syllables and vary song duration, whereas rattling cisticolas have relatively fixed song durations and ordering, but generate highly variable end-phrase forms (Benedict & Bowie, 2009). These two data points illustrate the potential for song variation to arise through many different avenues. Fixed features can take many forms, potentially allowing all 40 plus species of the morphologically

conserved cisticola warblers to signal species identity with song. These studies illustrate the importance of phenotypic features beyond morphology for species identification. They also emphasize the value of library resources Vasopressin Receptor for evaluating phenotypic features of problematic groups. Many forms of information, including sound archives with wide geographic sampling, are available to researchers wishing to examine current patterns of diversity and the resulting indicators of evolutionary processes. We thank the Wildlife Division of the British Library, the Macaulay Library of Natural Sounds and the Ditsong Museum of Natural History (Transvaal Museum) for providing song samples, as well as all of the authors who contributed to these valuable sound

depositories. This paper was improved by comments from Jay McEntee, Alex Kirschel, Tim Parker, Tereza Petruskova and an anonymous reviewer. Thanks are due to Kim Hoke for statistical advice. Funding to conduct this study was provided by the Museum of Vertebrate Zoology Alexander Fund. “
“Little is known about how season influences burrowing activity, burrow structure or reproductive behaviour in subterranean mammals. We excavated burrow systems of male and female Georychus capensis, a solitary, subterranean rodent, in winter (wet season) and summer (dry season) to investigate whether, if any, seasonal differences were due to putative mate-seeking behaviour of males. Burrow structure differed between seasons but not between sexes.

Thief pigeons are worth further study. The second example of promiscuity was one Darwin (1871) cited in Descent. The information came from his cousin

William Darwin Fox and involved the two species of geese he kept. In one season, a male Chinese goose seduced a white domestic goose, causing her to abandon her domestic gander: when the female’s clutch hatched, it was immediately evident from the appearance of the goslings that both the Chinese gander and the white gander had fathered offspring: promiscuity and multiple paternity in a single, striking example. With such clear evidence in front of him, it is easy (with the benefit of hindsight) to ask how Darwin could have overlooked the potential for promiscuity and sperm competition. In this instance, I think Victorian prudery won out over science (Birkhead, 1997), but Smith (1998) MAPK inhibitor Selleck KU-57788 offers

some other possibilities. He suggests that Darwin (and many of his successors) were psychologically predisposed to presume that females are monogamous. If so, the few explicit examples of female promiscuity that Darwin was aware of were then viewed as exceptions and could be ignored. Darwin may also have assumed pre-copulatory choice to preclude the necessity of female promiscuity. Finally, Smith (1998) suggests that during Darwin’s lifetime, knowledge of sexual reproduction was both amorphous and confused, creating an intellectual barrier that prevented Darwin from considering the implications of female promiscuity. As far as I am aware, there is no synthesis of what Darwin understood or did not understand about sexual reproduction in animals. He wrote extensively about the process of fertilization in plants, and so it is almost inconceivable that he did not have an interest in animal reproduction, and yet our understanding of Darwin’s knowledge of sexual reproduction remains Astemizole unclear. He knew a great deal about the reproductive anatomy of the barnacles

he spent so long dissecting. We also know from his notebooks (Barrett et al., 1987) that he had read Spallanzani’s (1769) ingenious study from the late 1700s that erroneously concluded that spermatozoa had no role in fertilization. As Smith (1998) points out, Spallazani’s account of fertilization must have confused Darwin, and continues: ‘Perhaps it was this confusion that pressed Darwin to his own fuzzy “gemmule” theory of inheritance [pangenesis], which despite its own vagaries at least restored a heritable male contribution to reproduction’. Smith then says: ‘Ideas about fertilisation and heredity remained extremely amorphous through the eighteenth and most of the nineteenth centuries …’. While it is certainly true that ideas about heredity remained amorphous, it is less clear why Darwin should have remained confused about sexual reproduction.

The comparison between patients with or without steatosis are shown in Table 2. By univariate analysis, ALT (P = 0.0004), AST (P = 0.0005), HOMA-IR (P = 0.0043), GGT (P = 0.0044), BMI (P = 0.0049), fasting insulin (P = 0.0050) and age (P = 0.0379) were significantly associated with liver steatosis. By multivariate analysis, L/S ratio (P = 0.012; OR, 0.501; CI, 0.29–0.86), AST (P = 0.022; OR, 1.253; CI, 1.03–1.52), and HOMA-IR (P = 0.041; OR, 1.335; CI, 1.01–1.76) were significantly associated with liver steatosis (Table 3). The percentage of steatosis was calculated by using Dynamic cell

count BZ-H1C Selleck Y27632 software after measuring the real steatotic area of liver specimens by BIOREVO BZ-9000 microscope. Figure 2 (a) shows the relationship between steatotic grades and percentage of steatosis. Percentage of steatosis was significantly correlated with the steatotic grade (r = 0.86, P = 1.85 × 10−18). L/S ratios were: S0, 1.16 ± 0.20 (mean ± SD); S1, 0.88 ± 0.28; S2, 0.76 ± 0.20; and S3, 0.40 ± 0.18, respectively (Fig. 2a). L/S ratio was negatively

correlated with steatotic grade (r = −0.77, P = 7.94 × 10−13) (Fig. 2b). Because the percentage of steatosis was evaluated from the liver specimens, this was expected to show the real fat deposition in the liver. Therefore, the relationship between the percentage of steatosis and L/S ratio was compared Urease (Fig. 3), and showed the significant negative correlation. Based on this curve, L/S ratio could Apitolisib manufacturer be expected by the formula: (−0.6356 × [log percentage of steatosis] + 1.2964). The AUROC for the diagnosis of steatosis was 0.886 for L/S ratio (Fig. 4). The optimum cut-off value for L/S ratio to exclude steatosis was 1.1 which produced sensitivity and specificity values of 83.3% and 93.3%, respectively, as well as a positive predictive value of 97.6% and a negative predictive value of 63.3%. THIS STUDY ATTEMPTED to elucidate

the accuracy of histological diagnosis of fatty deposition by pathologists and also to demonstrate the optimal cut-off value for the diagnosis of fatty liver on CT. As a result, evaluation by histological findings and steatotic grades assessed by a pathologist were comparatively accurate compared with imaging modalities such as CT in this case. That is, steatotic grades diagnosed by a pathologist were significantly correlated with the percentage of steatosis and L/S ratio. From the point of laboratory findings, patients with steatosis were younger, had higher BMI, and increased AST, ALT, GGT and HOMA-IR. By multivariate logistic regression analysis, AST and HOMA-IR were independently associated with steatosis. For the non-invasive assessment of liver steatosis, imaging analyses and histological findings were compared to elucidate the utility of L/S ratio on CT.

Conclusions: Silencing NGF may have a beneficial, anti-inflammatory and protective effect in acute hepatotoxicity models. The following people have nothing to disclose: Rafael Bruck, Einav Hubel, Isabel Zvibel Aim: The goal

of this study was to investigate the relationship between inflammation-related microRNAs and NAFLD patho-genesis in a rodent model with metabolic syndrome. Methods: Leptin receptor deficient (Leprdb/db) mice were fed a high fat diet or standard chow for 5 or 10 weeks. Liver histology was scored for steatosis, ballooning, inflammation, fibrosis and NAFLD activity score (NAS) by a hepatopathologist; and classified Autophagy Compound Library cell line into DM (diabetes mellitus), NAFL (nonalcoholic fatty liver) and NASH (nonalcoholic steatohepatitis) groups. Serum were analyzed for metabolic changes, and hepatic microRNA (miR-122, −146a, −155, and −223) levels were determined. Results: Greater find more than half of the mice fed high-fat diet developed NASH compared to controls. Mice with NAFL and NASH had elevated hepatic triglycerides,

serum aminotransferases, inflammatory cytokines (IL-6 and TNF-α), glucose and insulin levels. Expression of miR-155 and −223 (p<0.01 for both] were increased in NAFL and NASH mice, while miR-122 was decreased, relative to DM. Expression of miR-146a were also increased in the livers of NAFL and NASH mice compared to DM mice (p<0.03), though the extent of increase was smaller compared to miR155 and 223. Increased levels of miR155 correlated with upregulation of its transactivator and target, NF-KB, in NASH livers, indicated by increased phosphoryla-tion of the p65 subunit of NF-KB, and increased expression of MCP-1, an NF-KB regulated chemokine and CCR2, its cognate receptor. http://www.selleck.co.jp/products/carfilzomib-pr-171.html Consistent with the upregulation of miR-155 (and down-regulation of miR-122), we observed increased infiltration of macrophages in NASH livers indicated by increased F480 and Mac-2 staining; and elevated CD68, F480 and CD11b gene expression levels in the NASH livers, relative to DM. Also consistently,

T cell markers such as CD3gamma, IFN-gamma, MHCII and CD8 were upregulated in NASH livers. Regression analysis revealed that correlating miR-155 versus miR-223 gave a Pearson r of 0.91. These miRs were strongly associated with %mass increase (r=0.61, p<0.0001 for both), ALT & AST (r>0.56, p<0.001 for all), adiponectin (r<-0.50 for both, p<0.001), and NAS (Spearman r=0.50, p<0.001 for both). Conclusions: MicroRNAs associated with inflammation, especially miR155 and its known targets, were significantly altered in this mouse model of NASH, suggesting their involvement in cytokine/chemokine induction and immune cell recruitment and activation. The significant Pearson’s correlation between MiR-155 and miR-223 indicated that these microRNAs are involved in similar inflammatory cascades in NASH progression. These studies emphasize a key role for these microRNAs in NASH pathogenesis. Kris V.

Conclusions: Silencing NGF may have a beneficial, anti-inflammatory and protective effect in acute hepatotoxicity models. The following people have nothing to disclose: Rafael Bruck, Einav Hubel, Isabel Zvibel Aim: The goal

of this study was to investigate the relationship between inflammation-related microRNAs and NAFLD patho-genesis in a rodent model with metabolic syndrome. Methods: Leptin receptor deficient (Leprdb/db) mice were fed a high fat diet or standard chow for 5 or 10 weeks. Liver histology was scored for steatosis, ballooning, inflammation, fibrosis and NAFLD activity score (NAS) by a hepatopathologist; and classified Forskolin nmr into DM (diabetes mellitus), NAFL (nonalcoholic fatty liver) and NASH (nonalcoholic steatohepatitis) groups. Serum were analyzed for metabolic changes, and hepatic microRNA (miR-122, −146a, −155, and −223) levels were determined. Results: Greater CB-839 order than half of the mice fed high-fat diet developed NASH compared to controls. Mice with NAFL and NASH had elevated hepatic triglycerides,

serum aminotransferases, inflammatory cytokines (IL-6 and TNF-α), glucose and insulin levels. Expression of miR-155 and −223 (p<0.01 for both] were increased in NAFL and NASH mice, while miR-122 was decreased, relative to DM. Expression of miR-146a were also increased in the livers of NAFL and NASH mice compared to DM mice (p<0.03), though the extent of increase was smaller compared to miR155 and 223. Increased levels of miR155 correlated with upregulation of its transactivator and target, NF-KB, in NASH livers, indicated by increased phosphoryla-tion of the p65 subunit of NF-KB, and increased expression of MCP-1, an NF-KB regulated chemokine and CCR2, its cognate receptor. DNA ligase Consistent with the upregulation of miR-155 (and down-regulation of miR-122), we observed increased infiltration of macrophages in NASH livers indicated by increased F480 and Mac-2 staining; and elevated CD68, F480 and CD11b gene expression levels in the NASH livers, relative to DM. Also consistently,

T cell markers such as CD3gamma, IFN-gamma, MHCII and CD8 were upregulated in NASH livers. Regression analysis revealed that correlating miR-155 versus miR-223 gave a Pearson r of 0.91. These miRs were strongly associated with %mass increase (r=0.61, p<0.0001 for both), ALT & AST (r>0.56, p<0.001 for all), adiponectin (r<-0.50 for both, p<0.001), and NAS (Spearman r=0.50, p<0.001 for both). Conclusions: MicroRNAs associated with inflammation, especially miR155 and its known targets, were significantly altered in this mouse model of NASH, suggesting their involvement in cytokine/chemokine induction and immune cell recruitment and activation. The significant Pearson’s correlation between MiR-155 and miR-223 indicated that these microRNAs are involved in similar inflammatory cascades in NASH progression. These studies emphasize a key role for these microRNAs in NASH pathogenesis. Kris V.