5A]). Hepatic expression of SREBP-1c, ACC1, and FAS was higher in IL-6−/− mice but lower in IL-10−/− mice compared with those in

WT mice (Fig. 5A,B). Reduced expression of these genes in IL-10−/− mice was partially reversed in IL-10−/−IL-6−/− dKO mice (Fig. 5A,B). Activation of adenosine monophosphate-activated protein kinase (AMPK) plays a key role in controlling lipid metabolism by phosphorylating and subsequently inhibiting ACC and suppressing the expression of ACC and FAS through down-regulation of SREBP-1c.32 ACC is an important enzyme for fatty acid synthesis, which catalyzes the first step in de novo fatty acid biosynthesis by converting acetyl coenzyme A to malonyl coenzyme A. Malonyl coenzyme A acts as a potent inhibitor of fatty acid oxidation by inhibiting carnitine palmitoyltransferase 1 (CPT-1), BMN-673 which transports fatty acids into the mitochondria for oxidation.33, 34 As shown in Fig. 5, expression of activated (i.e., phosphorylated) AMPK (pAMPK) was significantly higher in IL-10−/− mice than that in WT mice in both the XL184 price STD and

HFD groups, whereas such up-regulation was diminished in IL-10−/−IL-6−/− mice. Expression of pAMPK was comparable between IL-6−/− mice and WT mice. Consistent with the elevated levels of pAMPK, IL-10−/− mice had higher levels of inhibited (i.e., phosphorylated) ACC1 (pACC1) compared with WT mice. Such elevated phosphorylated ACC1 was reduced in IL-10−/−IL-6−/− mice versus IL-10−/− mice. In addition, hepatic expression of CPT1 was higher in HFD-fed IL-10−/− mice compared with WT mice. An additional deletion of IL-6 reduced hepatic CPT1 expression in IL-10−/−IL-6−/− mice versus IL-10−/− mice. Expression of these lipid metabolism-associated genes were also examined in WT, IL-10−/−, and IL-10−/− STAT3Hep−/− mice (Fig. 6). Compared with WT mice, IL-10−/− mice had reduced expression of SREBP-1c, ACC1, and Exoribonuclease FAS but enhanced expression of pAMPK, pACC1, and CPT-1 in the liver. These

dysregulations were partially corrected in IL-10−/− STAT3Hep−/− mice. In this article, we have demonstrated that IL-10−/− mice have greater liver inflammatory response but less steatosis and liver injury compared with WT mice after feeding with an ETOH or HFD diet. Our data suggest that in our models, inflammatory response reduces rather than promotes steatosis through activation of hepatic IL-6/STAT3, which subsequently inhibits the expression of lipogenic genes (SREBP-1c, ACC1, and FAS). In concert, IL-6 up-regulates the expression of CPT-1 and activates AMPK, which in turn further attenuates the expression of SREBP-1c and its target genes and inhibits ACC1. We have integrated our findings in a model depicting the effects of inflammation on steatosis in IL-10−/− mice (Fig. 7).

In contrast, rifaximin has not been shown to have a significant side-effect profile,16 certainly when compared to other previously utilized antibiotics, although long-term data are not yet available. Some of the adverse effects of lactulose can be minimized with the use of lactitol (an analog of lactulose);17 however, this is not available worldwide. Overtreatment of lactulose can lead to the more serious side-effects of marked dehydration, hyponatremia, and worsening of hepatic encephalopathy.5 The dosing regime of rifaximin can check details be either fixed daily or cyclical,15 whereas lactulose does rely on some degree of patient adjustment to ensure approximately two to three semiformed

stools daily. Costing considerations are

not straightforward. While the direct cost of rifaximin compared to lactulose is marked, approximately $US1120 as opposed to $150 per month in the USA,15 the total annual costing of rifaximin has been reported to be less than lactulose when hospital admissions are taken into account.18 The role of rifaximin in the prevention or treatment of hepatic encephalopathy following an acute variceal bleed remains to be elucidated. Even if no further conclusive studies confirming the beneficial effect of lactulose occur, it is difficult to conceive of it being substituted as first-line therapy for hepatic encephalopathy. Its routine prophylactic use in the setting of an acute variceal bleed LY2157299 (post-initial stabilization and endoscopic

control of bleeding) seems intuitive. Perhaps prophylactic lactulose therapy should be considered for incorporation into acute variceal bleed practice guidelines as the “standard of care. “
“Hereditary hemochromatosis (HH) is an autosomal recessive disease caused by mutations in the HFE gene leading to increased iron absorption and deposition of iron in various organs, including the liver. It is the most common hereditary disorder in White people with a prevalence as high as one in 140 although phenotypic expression is much less common. It typically presents as asymptomatic elevation in iron studies IMP dehydrogenase but can present with abnormal liver enzymes and hepatomegaly. Arthralgias, loss of libido, diabetes and heart failure can occur due to iron deposition in other organs. The diagnosis relies on demonstration of a high iron saturation and ferritin. Testing for HFE gene mutations and liver biopsy can also be helpful. Treatment is based on depletion of iron through phlebotomy and improves survival. “
“A woman, aged 76, was admitted to hospital with abdominal pain that had persisted for 24 hours. On examination, she had a smooth mass in the right upper quadrant of her abdomen. Seventeen years previously, she had been diagnosed with two hepatic cysts; one had been treated by percutaneous sclerotherapy while the other had been left untreated.

Algae are critical parts of aquatic ecosystems that power food webs and biogeochemical cycling. Algae are also major sources of problems that threaten

many ecosystems goods and services when abundances of nuisance and toxic taxa are high. Thus, algae can be used to indicate ecosystem goods and services, which complements how algal indicators are also used to assess levels of contaminants and Selleck C59 wnt habitat alterations (stressors). Understanding environmental managers’ use of algal ecology, taxonomy, and physiology can guide our research and improve its application. Environmental assessments involve characterizing ecological condition and diagnosing causes and threats to ecosystems goods and services. Recent advances in characterizing condition include site-specific models that account for natural variability among habitats to better

estimate effects of humans. Relationships between algal assemblages and stressors caused by humans help diagnose stressors and establish targets for protection and restoration. Many algal responses to stressors have thresholds that are particularly important for developing stakeholder consensus for stressor management targets. Future research on the regional-scale resilience of algal assemblages, the ecosystem goods and services they provide, and methods for monitoring and forecasting change will improve water resource management. “
“Until the recent use of molecular markers, species Vincristine in vitro diversity of Lobophora, an ecologically important brown algal genus with a worldwide distribution in temperate and tropical seas, has been critically underestimated. Using a

DNA-based taxonomic approach, we re-examined diversity of the genus from New Caledonia in the Southwest Pacific Ocean. First, species were delineated using general mixed Yule coalescent-based and barcoding gap approaches applied to a mitochondrial cox3 data set. Flavopiridol (Alvocidib) Results were subsequently confirmed using chloroplast psbA and rbcL data sets. Species delimitation analyses agreed well across markers and delimitation algorithms, with the barcoding gap approach being slightly more conservative. Analyses of the cox3 data set resulted in 31–39 molecular operational taxonomic units (MOTUs), four of which are previously described species (L. asiatica, L. crassa, L. nigrescens s.l., L. pachyventera). Of the remaining MOTUs for which we obtained a representative number of sequences and results are corroborated across analyses and genes, we described 10 species de novo: L. abaculusa, L. abscondita, L. densa, L. dimorpha, L. gibbera, L. hederacea, L. monticola, L. petila, L. rosacea, and L. undulata. Our study presents an excellent case of how a traditional morphology-based taxonomy fails to provide accurate estimates of algal diversity.

Although it is conceivable that Latino individuals may have less risk for fibrosis as an ethnic group, it is likely that the lower frequency of advanced Cilomilast research buy fibrosis may be explained, at least in part, by the overall younger age of the Latino population in this study. A notable finding of this study is the differential effect of HOMA-IR on risk of NASH (versus non-NASH histology), such that HOMA-IR conferred an increased risk of NASH in non-Latino whites, but not in Latinos. We did not find a differential effect of HOMA-IR on the risk of advanced fibrosis. Several studies

have described racial and ethnic variations in NAFLD, primarily with respect to differences in frequency of the disorder, with consistent reporting

of increased frequency in Latino populations and decreased frequency among African Americans. 3, 4, 7, 8, 23 Although the NASH CRN was not designed to be a population-based study, within our group of study participants with NAFLD, we found an increased frequency of NASH histology among Latinos (63%), compared to non-Latino blacks (52%), which LDE225 in vitro is in keeping with previously published trends. Although many studies of racial and ethnic variation in NAFLD have focused primarily on the prevalence (or frequency) of the disorder, a few studies have delved further into metabolic associations of NAFLD in different

racial and ethnic groups. A recently published study by Lomonaco et al. compared Hispanic and Caucasian individuals with biopsy-proven NASH with respect to several metabolic features, including measures of adipose and hepatic insulin resistance. The investigators found no significant difference between Hispanic and Caucasian individuals with respect to NASH severity, but their data suggested that in Hispanic diabetic patients, there may be a trend toward increased risk for fibrosis progression, warranting further investigation. 24 In two separate Cyclooxygenase (COX) investigations from the population-based Dallas Heart Study, Browning et al. and Guerrero et al. investigated the well-described dissociation between NAFLD and stereotypical metabolic risk factors, such as insulin resistance and obesity, among different racial and ethnic groups. 3, 9 Using magnetic resonance spectroscopy (MRS) to detect hepatic steatosis in a multiethnic population-based sample, Browning et al. reported the highest prevalence of hepatic steatosis among Latinos (45%) and lowest prevalence of steatosis among African Americans (24%), with whites having an intermediate prevalence of 33%. They also speculated that the increased prevalence of hepatic steatosis among Latinos might be attributable to the high prevalence of obesity and insulin resistance in this ethnic group.

The association between −1195G>A and digestive system cancers was further stratified by ethnicity, and we only found significantly increased risk in Asians compared to Caucasians, although the between-groups heterogeneity test was not significant, except for the recessive model (P < 0.001 for the heterogeneity test between groups;

race can explain nearly 100% of the heterogeneity between groups by meta regression; the P-value of the dummy variable was 0.004 for race) (Table 3). We used the Funnel plot and Egger’s test to address potential publication bias in the available literature. As shown in Figure 2, for −1195G>A, the shape of the funnel plot seemed symmetrical in the dominant model comparison in digestive system cancers, suggesting the absence of publication check details bias. Egger’s test was then used to provide statistical evidence for funnel plot symmetry, which is more pronounced when the larger of the intercept deviated from zero in the linear regression analysis. We also did not find significant publication bias (P = 0.147 for −1195G>A in the dominant model GA/AA vs GG). In late 1980s, COX-2 was discovered and postulated to be distinct from the constitutive COX (COX-1), because its activity was not regulated by glucocorticoids but induced at sites of inflammation.66,67 Subsequently, a large body

of studies investigated the role of COX-2 in cancer development. Up to now, it has been well known that COX-2 plays a key role in the carcinogenic process, especially for digestive system cancers.10,11 Erlotinib chemical structure In our meta-analysis, the COX-2−1195 variant A allele was associated with significantly increased risk of digestive system

cancers, but not for other cancers. The −1195G>A polymorphism is within the promoter region, which contains several key cis-acting regulatory elements, and has decisive roles in the regulation of COX-2 transcription.68 Zhang et al. reported that −1195 G>A change created a transcriptional factor c-myeloblastosis oncogene-binding site, and the −1195 A allele displayed higher transcription activity and mRNA expression compared with the −1195 G allele.69 Because COX-2 overexpression can increase proliferation, inhibit apoptosis, and enhance the invasiveness of cancer cells, the increased risk for the variant A alleles is biologically Resveratrol plausible. COX-2−765G>C, also located in the promoter region, appears to disrupt a stimulatory protein 1 binding site, and leads to a 30% reduction of COX-2 promoter activity in vitro.70 In the current study, no significant association between COX-2−765G>C and the risk of both digestive system cancers and other cancers was observed. However, when we remove the three studies deviated from Hardy–Weinberg equilibrium, −765G>C was significantly associated with an increased risk of both total cancer and digestive system cancer. Further larger studies are needed to validate its real association with cancer risk.

However, immunogenetic influence has been poorly investigated and mainly confined to HLA-class

II serological polymorphisms, because of their central role in the adaptive response. Nevertheless, it has been suggested that the role of the immune defense system, as well as the relevance of the genetic background, could better explain the pathogenesis of HCV infection, and these factors have been examined.10, 11 In adult patients, genetic variations in the IL28B gene, an innate cytokine, have been associated with the response to IFN-α/ribavirin therapy and spontaneous clearance in HCV genotype 1.26-28 For this reason, we evaluated the role of Quizartinib mw IL28B polymorphism in HCV genotype 1 vertical transmission, transient viremia, and chronic infection in infants. This is the first study that attempts to describe both HCV-VT and the spontaneous clearance of HCV, taking into account the influence Selleck Sotrastaurin of IL28B polymorphism

in mothers and children. The data obtained indicate that the IL28B genotype of mothers and children does not influence HCV-VT. Nevertheless, in the chronic infection study, 83% of the infants with the CC genotype exhibited spontaneous clearance (transient viremia) versus only 22% of the children with a non-CC genotype. On the other hand, the maternal IL28B genotype did not influence HCV chronic infection. Multivariate analysis identified the infant’s Rs12979860 CC IL28B genotype as the only factor independently associated with the spontaneous clearance Prostatic acid phosphatase of HCV. To the best of our knowledge, the present study is the first one to identify IL28B Rs12979860 polymorphism as a predictor of HCV spontaneous clearance in infants infected with HCV genotype 1 by vertical transmission. More information is now needed to understand the mechanisms that underlie this association, as well as the clinical impact of IL28B polymorphisms on HCV infection. The multivariate

analysis performed clearly shows the distinction between the risk factors in HCV-VT and in chronic infection. In HCV-VT, a high HCV viral load was independently associated with HCV-VT, thus confirming the bivariate analysis and the data previously published, by ourselves and by others. These data suggest that the maternal characteristics are more important in HCV-VT than are those of the infants. However, in the chronic HCV infection study, the multivariate analysis showed that the only factor independently associated with HCV clearance was the infants’ IL28B genotype, which confirmed our hypothesis that in infected infants the host’s immunogenic influence is crucial to the HCV viral response. Finally, all retrospective analyses have inherent limitations, but we have tried to minimize their effects.

Results: Gallbladder was enlarged in 35 patients (89 [86-106] mL) and within normal

range in 42 (41 [35-47] mL). Patients with enlarged gallbladders did not significantly differ from others regarding gender (65% vs. 66% males), median age (43 vs. 42 years), time from diagnosis (5 vs. 5.5 years), body mass index (21.6 vs. 23.7), associated inflammatory bowel disease (71% vs. 50%), UDCA treatment (89% vs. 90%), other MRI features including cystic abnormalities (8.5% vs. 12%), clinical or histological parameters of liver disease (Mayo risk score of −0.18 [−0.45-0.27] vs. −0.005 [−0.63-0.56]). Notably, malignancy was less frequent in the group with enlarged gallbladder, occurring in 2 (5.7%) vs. 11 (26.2%) patients with normal gallbladder size (P=0.029). Colorectal cancer in particular was 6.7-fold less frequent, occurring in 1 (2.8%) Akt inhibitor vs. 8 (19%) patients (P=0.037, OR=6.7 [0.9- 354])). In patients with enlarged gallbladder, the serum concentrations of secondary bile acids were lower than in other patients (1.6 [1.3-1.9] vs. 2.5 [2-3.1]

μmol/L, P=0.0004). This was true for deoxycholic acid (0.7 [0.5-1] vs. 2.2 [1-6-3] μmol/L, P=0.0001), a secondary bile acid known to promote colon carcinogenesis. Patients in this group also had higher concentrations of primary bile acids (10.5 [6.6-16.7] vs. 4.3 [3.5-5.3] μmol/L, P=0.0001) selleck chemicals and of UDCA (44.0 [29.4-52] vs. 27.2 [14.6-31.1] μmol/L, P=0.001). Furthermore, they had higher serum concentrations of the gallbladder-relaxing hormone FGF19 (211.6 [168.6-234.6] vs. 88.6 [72.7-121.6] pg/mL, P=0.0001), 4��8C which concentration was correlated with gallbladder volume (R2=0.46, P=0.001) Conclusion: Gallbladder is enlarged in approximately half of PSC patients, which can be caused by increased FGF19 levels, and which is associated with a lack of secondary bile acids, enhanced UDCA enrichment and a lower prevalence of colorectal cancer, consistent with protective properties of gallbladder enlargement in PSC. Disclosures: Olivier Chazouillères – Consulting: APTALIS, MAYOLY-SPINDLER The following

people have nothing to disclose: Mourad Aissou, Lionel Arrivé, Dominique Rainteau, Sara Lemoinne, Astrid Donald D. Kemgang Fankem, Delphine Firrincieli, Nicolas Chignard, Christophe Corpechot, Chantal Housset [Background and Aims] Although it is well established that treatment with ursodeoxycholic acid (UDCA) improves long-term outcome in patients with primary biliary cirrhosis (PBC), it is still uncertain whether “early” PBC, with normal or low ALP levels and at early histological stages, would benefit from UDCA treatment. In Japan nationwide surveys for PBC have been performed every three year since 1980, and so far clinical data of 7,376 cases have been accumulated. In the current study we examined the long-term outcome of asymptomatic PBC patients with normal or low ALP and at early histological stages in whom UDCA treatment was not initiated.

12 Accordingly, in our current study we confirmed that UDCA-LPE was able to dampen the susceptibility of the liver toward extrinsic apoptosis as well as the inflammatory response, with a

pronounced down-regulation of mediators such as MCP1, VCAM1, or TNF-α, which are responsible for leukocyte recruitment to the site of inflammation. MCP1 has also been described to be involved in the process of Alpelisib mouse chemotaxis and fibrogenic activation of stellate cells,28, 29 leading to TGF-β1 and extracellular matrix production. Currently, our preliminary observations indicate that UDCA-LPE may be capable of impairing fibrotic response due to the MCD diet (unpublished data). Thus, based on ongoing experimental studies, potentially beneficial effects of UDCA-LPE on hepatofibrogenesis should be addressed in the MG132 future. Lipotoxicity attributable to potent proinflammatory lipid intermediates has been implicated in deteriorating parenchymal damage during NAFLD. The phospholipase A2 (PLA2) cleavage product LPC, which plays a pivotal role in different inflammatory conditions,30-32 mediates hepatocellular apoptosis due

to palmitate-induced lipotoxicity.33 Furthermore, LPC levels were found to be elevated in livers of NAFLD patients.4 Earlier studies showed that LPC abundance in mitochondria is able to induce hepatocellular death34 caused by mitochondrial membrane depolarization.35 Our results proved that UDCA-LPE is capable of lowering increased LPC pools in dietary NAFLD, as previously demonstrated for acute liver injury in vitro and in vivo.12 Additionally, HFD mice treated with UDCA-LPE displayed reduced serum activity of PLA2 (unpublished observations), which

Thiamet G was previously reported to be necessary for lipid droplet biogenesis.36 Thus, inhibition of PLA2 may serve as a further mechanism for how the conjugate prevents hepatic lipid accumulation by way of inflammation inhibition. Further experimental studies are needed to prove this hypothesis. Excessive hepatic fat deposits may further serve as a prerequisite for subsequent liver injury due to lipid peroxidation. Enhanced ROS formation in NASH may oxidize unsaturated lipids to generate lipid peroxidation products.37 In our study, treatment with UDCA-LPE achieved a marked reduction in lipid hydroperoxides in mice fed an MCD diet, which has been previously shown to cause extensive increase in these cytotoxic lipid byproducts.38 Hepatic fat accumulation accompanied by changes in lipid metabolism is an essential pathophysiological feature of NAFLD. In accordance with earlier studies in humans,39, 40 HFD mice displayed up-regulation of de novo lipogenesis with enhanced expression of FASN and ACC1 as well as a moderate increase in SREBP1c, which is largely responsible for the regulation of enzymes involved in fatty acid synthesis.

0. Results: Results Among the 2849 HBV complete genome sequences, 217(8%) strains with Y(I/V) DD were identified. Of them, 120 had YIDD mutation and 97 had YVDD mutation. 1543 strains (54.2%) with PC-BCP mutation, seven mutation patterns of G1896A, G1899A, G1896A-G1899A, A1762T/G1764A, A1762T/G1764A-G1896A, A1762T/G1764A-G1899A, A1762T/G1764A-G1896A-G1899A were identified. Among the Y(I/V) DD strains, 165 (76%) strains had PC-BCP mutations. YV/IDD mutation with higher incidence of PC-BCP mutations were detected than without YMDD mutation (76% vs 24.0%, χ2 = 45.283,

P = 0.000), YIDD mutation with higher incidence of PC-BCP mutations than YVDD mutation (85% vs 64.9%, χ2 = 11.836, P = 0.001) and lamivudine (LAM) resistance of YI/VDD mutation with higher incidence of PC-BCP mutations than pre-existent YI/VDD (89.3% vs 58.9%, χ2 = 27.084, P = 0.000). The three patterns of G1896A-G1899A BTK inhibitor mutation (P = 0.000, OR = 7.573), A1762T/G1764A- G1899A mutation (P = 0.000, OR = 6.539) and A1762T/G1764A-G1896A-G1899A mutations (P = 0.000, OR = 6.596) have a higher tendency to develop YIDD mutation according to binary logistic analysis. Conclusion: Conclusion There is a relationship between HBV YI/VDD mutation and PC-BCP mutations. Different PC-BCP mutation patterns have different effect on YI/VDD mutation. Key Word(s): 1. Hepatitis B virus;

2. Y(I/V) DD mutation; 3. PC-BCP mutations; Table 1 Relative risks of YI/VDD according selleck inhibitor to Binary logisticl analysis for difference Pre Core-basic core

promotoe mutation pattens Factors YIDD YVDD 相对危险度 OR (95%CI) P 值 相对危险度 OR (95%CI) P 值 ? G1896A-G1899A 7.573 0.000 0 0.996 (3.77–15.212) (0–0) ? A1762T/G1764A 4.497 0.000 2.494 0.000 (2.729–7.410 ) (1.568–3.96) ? A1762T/G1764A+ G1896A 6.103 0.000 3.575 0.000 (3.474–10.725) (2.074–6.161) ? A1762T/G1764 A+ G1899A 6.539 0.000 0 0.997 (2.402–17.799) (0–0) ? A1762T/G1764A+G1896AA+1899G 6.596 0.000 0 0.997 (2.757–15.785) (0–0) Presenting Author: QIANQIAN ZHANG Additional Authors: XIAOLIN GUO Corresponding Author: QIANQIAN ZHANG, XIAOLIN GUO Affiliations: the first hospital of Jilin university Objective: Nucleoside Ureohydrolase analogues of antiretroviral drugs currently widely listed are entecavir, lamivudine, telbivudine, adefovir dipivoxil, each of which has its advantages and disadvantages. And entecavir with strong antiviral effect, rapid onset, low resistance, especially for patients with initial treatment or severe conditions, is the best choice for antiviral treatment at present. To observe the decrease of viral load of hepatitis B, the improvement of liver function and blood coagulation function of the patient of hepatitis B associated with acute on chronic liver failure after antiviral treatment with application of entecavir 1.0 mg/day, we reviewed 1 case with acute on chronic hepatitis B liver failure in our hospital. Methods: The patients of acute on chronic hepatitis B liver failure was administrated entecavir of 0.

Methods: The changes of intracellular Ca2+ ([Ca2+]i) in HCC cells were examined using Alpelisib datasheet the Ca2+-sensitive dye Fura-2 AM. The cell proliferation was estimated with MTT and Edu assays, and the cell migration and invasion were estimated with scratch wound and transwell

assays. Results: TGF-β (10 ng/ml) rapidly stimulated [Ca2+]i increases in normal liver cell LO2 and hepatocellular carcinoma cell HepG2. Both 2-APB, a blocker of canonical transient receptor potential channels (TRPC6), and KB, a blocker of Na+/Ca2+ exchanger (NCX1) partially inhibited TGF-β-induced [Ca2+]i increase in HepG2(P < 0.05), and 2-APB had more markedly inhibitory effect than KB. In the absence of extracellular Ca2+, TGF-β did not induce significant the change of [Ca2+]i in HepG2 cells. The further study showed that the mRNA and protein expression levels of NCX1 and TRPC6 were obviously increased in HepG2 after incubation with TGF-β

for 24 hours. TGF-β promoted the cell proliferation, migration, and invasion in HepG2 cells, which was partially check details inhibited by both 2-APB and KB. Bapta-am, an intracellular calcium chelator, completely inhibited the effect of TGF-β on HepG2 cells. Conclusion: TGF-β regulates the cellular behavior of HCC through intracellular Ca2+ signal. TRPC6 and NCX1 were involved in the role of TGF-β on HCC cells. Key Word(s): 1. TGF-β; 2. HCC; 3. NCX1; 4. TRPC6; Presenting Author: BIGUANG TUO Additional Authors: RUI XIE, JINGYU XU, GUORONG WEN, HAI JIN, XUEMEI LIU, YUAN YANG, BEI JI, YIXIA JIANG, HUI DONG Corresponding Author: BIGUANG TUO Affiliations: Department of Gastroenterology, Affiliated Hospital of Zunyi Medical college Objective: P2Y2 receptor (P2Y2R) mediates a variety Thiamet G of biological functions. ATP is a physiologic ligand for P2Y2R, which can be released from inflammatory cells and tumor cells, and is an abundant biochemical component of the tumor microenvironment. It is well known

that chronic inflammation plays a key role in the development and progression of human hepatocellular carcinoma (HCC). In this study, we investigated the expression and role of P2Y2R in human HCC cells, which aimed to find a new therapeutic target against HCC. Methods: The experiments were performed in native isolated human HCC cells and normal hepatocytes, and human HCC cell lines. The xenograft model of human HCC was established in nude mice. Results: The mRNA and protein expressions of P2Y2R, not P2Y4R, in native human HCC cells and human HCC cell lines, HepG2 and BEL-7404, were markedly increased, compared to human normal hepatocytes and normal hepatocyte line LO2, respectively (P < 0.01 and P < 0.001). P2Y2R anatgonist suramin and specific siRNA, not P2Y4R specific siRNA, inhibited ATP-induced [Ca2+]i increases in HCC cells (P < 0.0001).