Medical procedures were common transmission risk factors; however

Medical procedures were common transmission risk factors; however, lifestyle-associated risk factors, including intravenous drug

abuse and tattoos or piercings, were more common in patients with HCV genotype 3 or 6. Most HCV-infected Han Chinese patients were IL28B genotype CC (rs12979860). HCV genotypes varied by geographic region, and disease characteristics differed according to HCV genotype. Relatively frequent detection of advanced liver disease may reflect limitations on access to antiviral Protein Tyrosine Kinase inhibitor therapy, and suggests that greater awareness of factors that influence HCV-associated disease may help avoid clinical complications and improve patient outcomes. “
“Dynamic contrast imaging techniques are considered the standard of care for the radiological diagnosis of hepatocellular carcinoma (HCC) in cirrhosis. However, the accuracy of radiological diagnosis depends largely on the degree of arterial hypervascularization, which increases with tumor size. Owing to the interplay and prognostic relevance of tumor vascularization and cell differentation, we asked ourselves whether tumor grade also affects the outcome of radiological Atezolizumab diagnosis. Sixty-two HCCs (47 of which measured 1-2 cm) were consecutively detected in 59 patients with compensated cirrhosis under surveillance with ultrasound and confirmed by way of echo-guided biopsy and concurrent investigations with contrast-enhanced ultrasound

(CE-US), computed tomography (CT), and gadolinium magnetic resonance imaging (MRI). Tumor cell differentiation was evaluated using Edmondson-Steiner criteria in liver cores of 0.9-5.0 cm (median 1.6 cm). Eighteen (29%) HCCs were grade I (1.5 cm), 28 (45%) were grade II (1.5 cm), 16 (26%) were grade III (1.8 MCE cm), and none were grade

IV. Contrast wash-in and wash-out were concurrently demonstrated in 21 (34%) tumors by way of CE-US, including three (16%) grade I and 18 (41%) grade II-III (P = 0.08); in 32 (52%) tumors by way of CT, including three (16%) grade I and 29 (66%) grade II-III (P = 0.0006); and 28 (47%) tumors by way of MRI, including three grade I (16%) and 25 (57%) grade II-III (P = 0.01). Among 1- to 2-cm tumors, the radiological diagnosis was achieved in two of 16 grade I and 17of 31 grade II-III tumors (P = 0.006). Conclusion: Tumor grade, a relevant predictor of disease severity, influences the accuracy of dynamic contrast techniques in the diagnosis of HCC. HEPATOLOGY 2010 Surveillance with abdominal ultrasound (US) of patients with cirrhosis, who are at risk of hepatocellular carcinoma (HCC), is the standard of care to detect small, potentially curable tumors.1 A standardized recall policy for liver nodules detected on US examination has been established that uses dynamic contrast imaging techniques to show the pathognomonic pattern of contrast wash-in in the arterial phase followed by wash-out in the venous phase.

Medical procedures were common transmission risk factors; however

Medical procedures were common transmission risk factors; however, lifestyle-associated risk factors, including intravenous drug

abuse and tattoos or piercings, were more common in patients with HCV genotype 3 or 6. Most HCV-infected Han Chinese patients were IL28B genotype CC (rs12979860). HCV genotypes varied by geographic region, and disease characteristics differed according to HCV genotype. Relatively frequent detection of advanced liver disease may reflect limitations on access to antiviral selleckchem therapy, and suggests that greater awareness of factors that influence HCV-associated disease may help avoid clinical complications and improve patient outcomes. “
“Dynamic contrast imaging techniques are considered the standard of care for the radiological diagnosis of hepatocellular carcinoma (HCC) in cirrhosis. However, the accuracy of radiological diagnosis depends largely on the degree of arterial hypervascularization, which increases with tumor size. Owing to the interplay and prognostic relevance of tumor vascularization and cell differentation, we asked ourselves whether tumor grade also affects the outcome of radiological selleck diagnosis. Sixty-two HCCs (47 of which measured 1-2 cm) were consecutively detected in 59 patients with compensated cirrhosis under surveillance with ultrasound and confirmed by way of echo-guided biopsy and concurrent investigations with contrast-enhanced ultrasound

(CE-US), computed tomography (CT), and gadolinium magnetic resonance imaging (MRI). Tumor cell differentiation was evaluated using Edmondson-Steiner criteria in liver cores of 0.9-5.0 cm (median 1.6 cm). Eighteen (29%) HCCs were grade I (1.5 cm), 28 (45%) were grade II (1.5 cm), 16 (26%) were grade III (1.8 MCE公司 cm), and none were grade

IV. Contrast wash-in and wash-out were concurrently demonstrated in 21 (34%) tumors by way of CE-US, including three (16%) grade I and 18 (41%) grade II-III (P = 0.08); in 32 (52%) tumors by way of CT, including three (16%) grade I and 29 (66%) grade II-III (P = 0.0006); and 28 (47%) tumors by way of MRI, including three grade I (16%) and 25 (57%) grade II-III (P = 0.01). Among 1- to 2-cm tumors, the radiological diagnosis was achieved in two of 16 grade I and 17of 31 grade II-III tumors (P = 0.006). Conclusion: Tumor grade, a relevant predictor of disease severity, influences the accuracy of dynamic contrast techniques in the diagnosis of HCC. HEPATOLOGY 2010 Surveillance with abdominal ultrasound (US) of patients with cirrhosis, who are at risk of hepatocellular carcinoma (HCC), is the standard of care to detect small, potentially curable tumors.1 A standardized recall policy for liver nodules detected on US examination has been established that uses dynamic contrast imaging techniques to show the pathognomonic pattern of contrast wash-in in the arterial phase followed by wash-out in the venous phase.

Medical procedures were common transmission risk factors; however

Medical procedures were common transmission risk factors; however, lifestyle-associated risk factors, including intravenous drug

abuse and tattoos or piercings, were more common in patients with HCV genotype 3 or 6. Most HCV-infected Han Chinese patients were IL28B genotype CC (rs12979860). HCV genotypes varied by geographic region, and disease characteristics differed according to HCV genotype. Relatively frequent detection of advanced liver disease may reflect limitations on access to antiviral HCS assay therapy, and suggests that greater awareness of factors that influence HCV-associated disease may help avoid clinical complications and improve patient outcomes. “
“Dynamic contrast imaging techniques are considered the standard of care for the radiological diagnosis of hepatocellular carcinoma (HCC) in cirrhosis. However, the accuracy of radiological diagnosis depends largely on the degree of arterial hypervascularization, which increases with tumor size. Owing to the interplay and prognostic relevance of tumor vascularization and cell differentation, we asked ourselves whether tumor grade also affects the outcome of radiological Cobimetinib chemical structure diagnosis. Sixty-two HCCs (47 of which measured 1-2 cm) were consecutively detected in 59 patients with compensated cirrhosis under surveillance with ultrasound and confirmed by way of echo-guided biopsy and concurrent investigations with contrast-enhanced ultrasound

(CE-US), computed tomography (CT), and gadolinium magnetic resonance imaging (MRI). Tumor cell differentiation was evaluated using Edmondson-Steiner criteria in liver cores of 0.9-5.0 cm (median 1.6 cm). Eighteen (29%) HCCs were grade I (1.5 cm), 28 (45%) were grade II (1.5 cm), 16 (26%) were grade III (1.8 medchemexpress cm), and none were grade

IV. Contrast wash-in and wash-out were concurrently demonstrated in 21 (34%) tumors by way of CE-US, including three (16%) grade I and 18 (41%) grade II-III (P = 0.08); in 32 (52%) tumors by way of CT, including three (16%) grade I and 29 (66%) grade II-III (P = 0.0006); and 28 (47%) tumors by way of MRI, including three grade I (16%) and 25 (57%) grade II-III (P = 0.01). Among 1- to 2-cm tumors, the radiological diagnosis was achieved in two of 16 grade I and 17of 31 grade II-III tumors (P = 0.006). Conclusion: Tumor grade, a relevant predictor of disease severity, influences the accuracy of dynamic contrast techniques in the diagnosis of HCC. HEPATOLOGY 2010 Surveillance with abdominal ultrasound (US) of patients with cirrhosis, who are at risk of hepatocellular carcinoma (HCC), is the standard of care to detect small, potentially curable tumors.1 A standardized recall policy for liver nodules detected on US examination has been established that uses dynamic contrast imaging techniques to show the pathognomonic pattern of contrast wash-in in the arterial phase followed by wash-out in the venous phase.

ING5 might be an important target gene of miR-196a Key Word(s):

ING5 might be an important target gene of miR-196a. Key Word(s): 1. microRNA; 2. miR-196a; 3. ING5; 4. pancreatic cancer; Presenting Author: JUN TIE Additional Authors: ZHUOLI ZHANG, CHUANGYE HE, ZHANXIN YIN, YANHONG LI, WENGANG GUO, JING NIU, FEIFEI WU, ANDREWC. LARSON, DAIMING FAN, GUOHONG HAN Corresponding Author: JUN TIE, GUOHONG HAN Affiliations: Xijing Hospital of Digestive Disease;

Department of Radiology, Feinberg School of Medicine, Northwestern University; Departments of Radiology and Biomedical Engineering, Northwestern University Objective: This study sought to retrospectively analyze the efficacy and safety of a port-catheter drug delivery system (PCS) implanted via left subclavian artery for Maraviroc gemcitabine administration during the treatment of advanced pancreatic cancer. Methods: Eighty patients with advanced pancreatic cancer who met our inclusion criteria were enrolled in the study and received gemcitabine through a PCS. We retrospectively analyzed the clinical benefit response Adriamycin cell line (CBR), tumor

objective response rate (ORR), overall survival (OS), drug toxicity, and surgical complications. Results: The CBR rate was 56.0% (45/80) and mainly manifested as pain relief and reduced analgesic drug use. Among the 80 patients enrolled, 9 cases had a partial response (11.3%), 27 cases had stable disease (33.8%) and 16 cases developed

progressive disease (20.0%). The ORR was 11.3% and the disease control rate was 45.0%. The median survival time was 160 days, and the 1-year survival rate was 23.3%. Univariate and multivariate Cox medchemexpress proportional hazards models for predictors of OS showed that obstructive jaundice, ECOG score, number of chemotherapy treatments, and metastasis were independent factors that affected the prognosis of patients with advanced pancreatic cancer. Drug toxicity manifested mainly as mild bone marrow suppression, nausea, and vomiting. The most common interventional complication was port-catheter blockage (2/80, 2.5%) and catheter tip dislocation (3/80, 3.8%). Conclusion: Interventional chemotherapy via a PCS can significantly increase the CBR of patients, improve quality of life, and reduce systemic toxicity. Thus, this approach can be considered a safe and effective treatment for advanced pancreatic cancer. Key Word(s): 1. pancreatic cancer; 2. PCS; 3. gemcitabine; 4. treatment outcome; Presenting Author: YIQI DU Additional Authors: ZHAOSHEN LI Corresponding Author: YIQI DU Affiliations: Department of Gastroenterology, Changhai Hospital Objective: Detection of pancreatic cancer (PDAC), particularly at early stages, remains a great challenge owing to lack of specific biomarkers.

ING5 might be an important target gene of miR-196a Key Word(s):

ING5 might be an important target gene of miR-196a. Key Word(s): 1. microRNA; 2. miR-196a; 3. ING5; 4. pancreatic cancer; Presenting Author: JUN TIE Additional Authors: ZHUOLI ZHANG, CHUANGYE HE, ZHANXIN YIN, YANHONG LI, WENGANG GUO, JING NIU, FEIFEI WU, ANDREWC. LARSON, DAIMING FAN, GUOHONG HAN Corresponding Author: JUN TIE, GUOHONG HAN Affiliations: Xijing Hospital of Digestive Disease;

Department of Radiology, Feinberg School of Medicine, Northwestern University; Departments of Radiology and Biomedical Engineering, Northwestern University Objective: This study sought to retrospectively analyze the efficacy and safety of a port-catheter drug delivery system (PCS) implanted via left subclavian artery for Topoisomerase inhibitor gemcitabine administration during the treatment of advanced pancreatic cancer. Methods: Eighty patients with advanced pancreatic cancer who met our inclusion criteria were enrolled in the study and received gemcitabine through a PCS. We retrospectively analyzed the clinical benefit response this website (CBR), tumor

objective response rate (ORR), overall survival (OS), drug toxicity, and surgical complications. Results: The CBR rate was 56.0% (45/80) and mainly manifested as pain relief and reduced analgesic drug use. Among the 80 patients enrolled, 9 cases had a partial response (11.3%), 27 cases had stable disease (33.8%) and 16 cases developed

progressive disease (20.0%). The ORR was 11.3% and the disease control rate was 45.0%. The median survival time was 160 days, and the 1-year survival rate was 23.3%. Univariate and multivariate Cox MCE公司 proportional hazards models for predictors of OS showed that obstructive jaundice, ECOG score, number of chemotherapy treatments, and metastasis were independent factors that affected the prognosis of patients with advanced pancreatic cancer. Drug toxicity manifested mainly as mild bone marrow suppression, nausea, and vomiting. The most common interventional complication was port-catheter blockage (2/80, 2.5%) and catheter tip dislocation (3/80, 3.8%). Conclusion: Interventional chemotherapy via a PCS can significantly increase the CBR of patients, improve quality of life, and reduce systemic toxicity. Thus, this approach can be considered a safe and effective treatment for advanced pancreatic cancer. Key Word(s): 1. pancreatic cancer; 2. PCS; 3. gemcitabine; 4. treatment outcome; Presenting Author: YIQI DU Additional Authors: ZHAOSHEN LI Corresponding Author: YIQI DU Affiliations: Department of Gastroenterology, Changhai Hospital Objective: Detection of pancreatic cancer (PDAC), particularly at early stages, remains a great challenge owing to lack of specific biomarkers.

120% ± 0005% However, this number varied according to the consi

120% ± 0.005%. However, this number varied according to the considered amino acid position. Therefore, only substitution frequencies higher than the mean maximal error rate for the corresponding amino acid position plus 2 SDs were taken into account in the analysis. Plasmids were tested in triplicate at different dilutions ranging from selleck chemical 5 × 103 to 108 copies/mL. No effect of the

DNA amount on UDPS results was observed (data not shown). UDPS was then applied to serum samples taken at baseline and frequently during therapy, representing a total of 119 serial samples from 7 patients who developed resistance to adefovir monotherapy (15-24

samples per patient). Approximately 480,000 sequences (111 Mbp) were generated, with 4,010 ± 843 sequences per sample and a mean length of 382 ± 31 nucleotides (nt) after eliminating excessively short sequences (≤50 nt). Overall, 10.2% of the generated sequences were eliminated by the software because of inadequate quality. Table 1 shows the prevalence of amino acid substitutions known to confer HBV resistance to nucleoside/nucleotide analogs detected by UDPS at baseline in the 7 patients. Five samples were found to harbor rtA181V/T substitutions, SCH727965 manufacturer one harbored the rtN236T substitution, and two harbored rtM204V/I substitutions. No substitutions known to improve the fitness of rtM204V/I variants in

the presence of lamivudine, telbivudine, or entecavir (rtV173L and rtL180M) were found in baseline samples. One sample harbored the rtT184S/A/I/L substitution and none medchemexpress harbored the rtR202G substitution; both these substitutions are known to confer full resistance to entecavir when associated with rtM204V/I and rtL180M. Table 1 also shows the prevalence of amino acid substitutions known to confer HBV resistance to nucleoside/nucleotide analogs detected by UDPS in the two comparator groups described in the Patients and Methods section. Among the 5 HBeAg-positive patients who seroconverted and maintained undetectable HBV DNA levels after adefovir therapy, 2 were found to harbor rtA181V/T substitutions at baseline, whereas none harbored the rtN236T substitution; 2 harbored rtM204V/I substitutions, including 1 in whom it represented nearly 10% of the viral quasispecies and was associated with an rtL180M substitution, suggesting earlier exposure to lamivudine; rtT184S/A/I/L and rtR202G substitutions were found in 1 and 1 patient, respectively.

3B-h) To further dissect how AR regulates MMP-9 at the transcrip

3B-h). To further dissect how AR regulates MMP-9 at the transcriptional level, we constructed an MMP-9 promoter (ranged from

+2 to −2629) hooked with a luciferase vector to test whether AR could negatively regulate MMP-9 promoter transactivation activity, and found that AR could suppress MMP-9 expression in promoter regulation (Supporting Fig. 7A-C). We also applied the zymography assay to detect MMP-9 activity, and found higher Ceritinib in vitro MMP-9 proteolytic activity in ARKO BM-MSCs, compared with WT BM-MSCs (Fig. 3B-i). This was also confirmed in studies using hMSCs manipulated with AR-siRNA (Supporting Fig. 6C,F). To test whether ARKO-mediated enhanced migration is MMP-9 dependent, we pretreated ARKO BM-MSCs with an MMP-9 inhibitor and performed the migration assay, and results showed that the addition of the MMP-9 inhibitor indeed masked ARKO-mediated enhanced migration ability (Fig. 3B-j), suggesting that AR needs to go through MMP-9 to exert its influence on BM-MSC migration. Together, results from three different types of assays all proved that MMP-9 is a critical molecule to mediate the enhanced www.selleckchem.com/products/ganetespib-sta-9090.html migration ability of ARKO BM-MSCs. Finally, we confirmed the above-described findings showing KO of AR in BM-MSCs increased self-renewal potential and migration capacity in CCl4-induced liver cirrhotic mice. Consistently, ARKO BM-MSCs-transplanted liver showed higher Ki67/GFP double-positive

stained cells (representing proliferating transplanted BM-MSCs) than WT BM-MSCs (Fig. 3C-k-m). To correlate the increased self-renewal and migration potentials of ARKO BM-MSCs improvement in anti-fibrosis and anti-inflammatory 上海皓元 actions, we used conditioned medium (CM) of BM-MSCs to test their effects on macrophage migration and HSCs proliferation. Results showed that BM-MSCs-inhibited macrophage migration (anti-inflammatory effects) and HSCs proliferation (anti-fibrotic actions) were BM-MSCs-number dependent (Fig. 3D,E), suggesting

that KO of AR-increased self-renewal and migration of BM-MSCs resulted in more BM-MSCs to exert better anti-inflammation and anti-fibrotic actions. Together, results (from Fig. 3A-E) concluded that KO of AR in BM-MSCs led to increased self-renewal and migration potentials of BM-MSCs and these resulted in better transplantation therapeutic efficacy to treat liver cirrhosis by exerting better anti-fibrotic and anti-inflammatory effects. These phenotypes were involved in the modulation of EGF-Erk1/2/Akt signals, as well as MMP-9 signals. All above-described results demonstrated that higher numbers of BM-MSCs migrating into the cirrhotic liver led to better transplantation therapeutic efficacy with higher anti-inflammatory and anti-fibrotic effects (Fig. 3D,E). We were interested to know whether there are any secreted paracrine factors influenced by knockout of AR in BM-MSCs to contribute to anti-inflammatory and -fibrotic actions.

e illumination) and direct cues (ie predator odour) did not G

e. illumination) and direct cues (i.e. predator odour) did not. Giving-up-density at above-ground feeders was always lower than at on-ground feeders. Possums spent more time and foraged more at the above-ground feeders than at the on-ground feeders. Our results demonstrate that when multiple cues are present, varying in

the accuracy of the information they provide about predation risk, possums AZD6738 cost respond to habitat-related cues. Possums manage risk by modifying behaviours, reducing time spent foraging in areas where potential risk is perceived as high. Thus, when the location of a predator at a certain point in time and space is unknown, and food demands are high, habitat-related cues are a safe choice to assess predation risk, with reliable returns for free-ranging herbivores. “
“The Atlantic forest of Brazil is a biodiversity hot spot, but is extremely fragmented. Local extinction of important seed dispersers, such

as primates, threatens the maintenance of these fragments. It is important to evaluate the capacity of fragment-tolerant species to disperse seeds and help maintain plant communities within fragments. Green iguanas Iguana iguana are large, fragment-tolerant, canopy-dwelling lizards and have been noted to disperse seeds. We described the seed dispersal patterns buy INK 128 produced by green iguanas in six urban forest fragments (1.2–8 ha in size) in the Atlantic forest of north-east Brazil, over 20 months. A total of 294 seeds were counted in 321 scats, and 12 plant species were dispersed. The largest seeds dispersed were 14.9 mm long and up to 9.2 mm wide. Iguanas deposited 86.9% medchemexpress of scats within latrines, which

were used over a mean of at least 9 months. We show that iguanas can be effective seed dispersers and might partially replicate deposition patterns produced by howler monkeys in other studies. It is critical that we improve our understanding on the functional roles played by these cryptic, yet common, iguanas in order to determine whether they could buffer the negative effects caused by the local extinction of primates from forest fragments. “
“Home range size of terrestrial animals may be influenced by spatiotemporal dynamics of resources. However, little is known regarding the effects of spatiotemporal resource availability on semi-aquatic central place foragers such as the American beaver Castor canadensis. From January 2011 to April 2012, 26 beavers at 11 wetlands at Redstone Arsenal in north-central Alabama, USA, were captured and radio-tracked using radio telemetry.

e illumination) and direct cues (ie predator odour) did not G

e. illumination) and direct cues (i.e. predator odour) did not. Giving-up-density at above-ground feeders was always lower than at on-ground feeders. Possums spent more time and foraged more at the above-ground feeders than at the on-ground feeders. Our results demonstrate that when multiple cues are present, varying in

the accuracy of the information they provide about predation risk, possums HSP inhibitor respond to habitat-related cues. Possums manage risk by modifying behaviours, reducing time spent foraging in areas where potential risk is perceived as high. Thus, when the location of a predator at a certain point in time and space is unknown, and food demands are high, habitat-related cues are a safe choice to assess predation risk, with reliable returns for free-ranging herbivores. “
“The Atlantic forest of Brazil is a biodiversity hot spot, but is extremely fragmented. Local extinction of important seed dispersers, such

as primates, threatens the maintenance of these fragments. It is important to evaluate the capacity of fragment-tolerant species to disperse seeds and help maintain plant communities within fragments. Green iguanas Iguana iguana are large, fragment-tolerant, canopy-dwelling lizards and have been noted to disperse seeds. We described the seed dispersal patterns selleck inhibitor produced by green iguanas in six urban forest fragments (1.2–8 ha in size) in the Atlantic forest of north-east Brazil, over 20 months. A total of 294 seeds were counted in 321 scats, and 12 plant species were dispersed. The largest seeds dispersed were 14.9 mm long and up to 9.2 mm wide. Iguanas deposited 86.9% MCE of scats within latrines, which

were used over a mean of at least 9 months. We show that iguanas can be effective seed dispersers and might partially replicate deposition patterns produced by howler monkeys in other studies. It is critical that we improve our understanding on the functional roles played by these cryptic, yet common, iguanas in order to determine whether they could buffer the negative effects caused by the local extinction of primates from forest fragments. “
“Home range size of terrestrial animals may be influenced by spatiotemporal dynamics of resources. However, little is known regarding the effects of spatiotemporal resource availability on semi-aquatic central place foragers such as the American beaver Castor canadensis. From January 2011 to April 2012, 26 beavers at 11 wetlands at Redstone Arsenal in north-central Alabama, USA, were captured and radio-tracked using radio telemetry.

5) This suggests that elevated liver STAT3 activation in STAT3 m

5). This suggests that elevated liver STAT3 activation in STAT3 mice likely contributes to the resistance CP-690550 supplier of these mice to CCl4-induced liver necrosis and oxidative stress. This concept is further supported by conclusive evidence showing that deletion of STAT3 in hepatocytes restores liver necrosis in STAT3 mice after CCl4 administration (Fig. 7). Interestingly, STAT3 mice are resistant to CCl4-induced liver necrosis as demonstrated in the current study but more susceptible to Con A–induced T cell hepatitis despite enhanced STAT3 activation in the liver (Fig. 2 in Lafdil et al.28). This discrepancy could be attributable

to the deletion of STAT3 in myeloid cells preferentially enhancing the Th1 cytokine (IFN-γ) response during Con A–induced T cell hepatitis, dominating over the hepatoprotective effect of STAT3 and resulting in accelerated liver injury in this model.28 Such preferential induction of IFN-γ was not observed in STAT3 mice in the Paclitaxel chemical structure CCl4-induced liver injury model (2500 pg/mL serum IFN-γ in Con A model28 versus 25 pg/mL IFN-γ in CCl4 model in STAT3 mice in the current study). In addition, STAT3 mice are also more susceptible to chronic ethanol feeding-induced liver inflammation and injury.27 It has been well documented that chronic ethanol consumption inhibits STAT3 activation in the liver.30 Therefore, it is probable that chronic ethanol feeding

diminishes hepatic STAT3 activation and abolishes the hepatoprotective effect of STAT3 in STAT3 mice, medchemexpress resulting in enhanced liver injury in this alcohol-induced liver injury model.27 We have previously shown that STAT3 activation in hepatocytes promotes liver inflammation in alcohol-induced liver injury.27 Our findings in current studies showed that STAT3 activation in hepatocytes also plays a proinflammatory

role in CCl4-induced liver injury because deletion of STAT3 reduced systemic and hepatic inflammation although it enhanced CCl4-induced liver damage (Fig. 5). In addition, an additional deletion of STAT3 in hepatocytes enhanced CCl4-induced liver necrosis but partially counteracted the strong inflammation in STAT3 mice after CCl4 administration (Fig. 8). This is probably because deletion of STAT3 in hepatocytes reduced the hepatic expression of several STAT3-controlled inflammatory mediators (such as complement 3/5, IL-1, macrophage inflammatory protein 2, monocyte chemotactic protein 1, and intercellular adhesion molecule 1) in STAT3 mice (Fig. 7). Taken together, these findings suggest that enhanced hepatocellular STAT3 activation in STAT3 mice may contribute to not only the reduced liver necrosis but also the enhanced inflammation after CCl4 administration in these mice. In addition, elevated nuclear factor kappaB activation (Supporting Fig. S3) also may contribute to the reduced necrosis in STAT3 mice because of the hepatoprotective functions of nuclear factor kappaB.