Ya-Ju Du

Celecoxib attenuates liver steatosis and inflammation in non-alcoholic steatohepatitis induced by high-fat diet in rats

Cyclooxygenase-2 (COX-2) is involved in the process of non-alcoholic steatohepatitis (NASH). However, the role of the COX-2 inhibitor in NASH has not yet been elucidated. Therefore, in the present study, we investigated the role of celecoxib in a rat model of NASH induced by a high-fat diet (HFD). Wistar rats were administered HFD by gavage, and rats administered normal saline by gavage served as the controls. After 4 weeks of HFD feeding, the rats were treated with celecoxib (20 mg/kg/day) or placebo for 4 weeks. At the end of 4 and 8 weeks, histological changes in the livers of the rats were analyzed using hematoxylin and eosin; blood was collected to detect biochemical indicators (serum aminotransferase and triglyceride). Liver triglyceride content was measured using the triglyceride E-test kit. The liver expression of COX-2, nuclear factor-κ enhancer binding protein (NF-κB) subunits p50 and p65 was measured by real-time reverse transcription-polymerase chain reaction and/or Western blotting. Infiltration of steatosis and inflammation in cells was observed in the livers after 4 weeks of HFD administration, and marked steatosis and inflammation was induced after 8 weeks. These histological changes were significantly attenuated after celecoxib treatment. Reduced serum alanine aminotransferase and triglyceride (TG) levels and TG content in the liver were observed in the HFD rats that received celecoxib. Moreover, celecoxib suppressed hepatic COX-2 messenger RNA and protein expression. The NF-κB subunit p50 and p65 protein levels in the HFD rats were also attenuated after celecoxib treatment. The results indicate that the induction of COX-2 occurs in association with NF-κB activation in HFD-induced NASH rats. Celecoxib may protect against the development of steatohepatitis induced by HFD.

PREVALENCE OF HELICOBACTER PYLORI VACA, CAGA AND ICEA GENOTYPES AND CORRELATION WITH CLINICAL OUTCOME

The aim of this study was to assess the genetic status of cagA, vacA subtype and iceA genotypes of Helicobacter pylori and the relationship with upper gastrointestinal diseases in Northeast China. Gastric biopsies were obtained from 378 patients with upper gastrointestinal diseases and 197 samples were used. The cagA, vacA alleles and iceA genotypes were determined by polymerase chain reaction. CagA was present in 176 (89.3%) of 197 patients. Of the 197 cases, 186 (94.4%) had vacA signal sequence s1c allele, 6 (3%) had s1a and 5 (2.5%) had s1b. The vacA s2 genotype was not detected in our study. VacA middle region sequences, m1 and m2, were found in 20 (10.2%) and 150 (76.1%), respectively. The allelic variant iceA1 (70.1%) was more prevalent than iceA2 (23.4%). The vacA allele s1am2 had a significant relationship with the presence of gastric cancer (p<0.05) and the iceA1 genotype was also associated with gastric cancer (p<0.05). These may be useful risk factors for upper gastrointestinal diseases.

Endostar, a novel human recombinant endostatin, attenuates liver fibrosis in CCl4-induced mice

Decreasing hepatic fibrosis remains one of the major therapeutic challenges in hepatology. The present study aims to evaluate the effect of Endostar on both CCl4-induced liver fibrosis in mice and a hepatic stellate cell (HSC) line. Two main models were studied: (i) a liver fibrosis model was induced in BALB/c mice using CCl4 by intraperitoneal injection for six weeks. Six animal groups were studied: group 1: normal animals; group 2: CCl4-induced liver fibrosis; group 3: CCl4 + Endostar 20 mg/kg/d, six weeks; group 4: CCl4 + Endostar 10 mg/kg/d, six weeks; group 5: CCl4 + Endostar 20 mg/kg/d, four weeks; group 6: CCl4 + Endostar 10 mg/kg/d, four weeks corresponded to different Endostar doses and duration of administration. Liver fibrosis was evaluated by histopathological staining and liver hydroxyproline content. Expressions of collagen type I, α-smooth muscle actin (α-SMA), TGF-β1 and VEGFR were measured by real-time polymerase chain reaction (PCR). (ii) A liver cell model. HSC-T6 cells were cultured with or without Endostar for 12 h or 24 h. Expressions of collagen type I, α-SMA, and TGF-β1 were measured by real-time PCR. Collagen I and transforming growth factor β1 (TGF-β1) contents in cell supernatant were measured by enzyme-linked immunosorbent assay. As compared to the group without Endostar, liver fibrosis scores and hydroxyproline content were decreased in both Endostar groups (P < 0.05). Moreover, Endostar inhibited the hepatic expression of α-SMA, TGF-β1, Collagen-1, VEGFR1, and VEGFR2 mRNA (P < 0.05). In the HSC-T6 cell line model, Endostar profoundly inhibited the expression of α-SMA, Collagen-1, and TGF-β1 mRNA. Expressions of Collagen-1 and TGF-β1 protein were decreased in the Endostar group as compared to the normal controls in the supernatant of HSC-T6 cells (P < 0.05). Endostar decreased both liver fibrosis in CCl4-induced mice and collagen synthesis in HSCs in vitro. Therefore, this recombinant human endostatin is a promising compound for counteracting liver fibrosis.

Association of body mass index and smoking on outcome of Chinese patients with colorectal cancer

BackgroundThe impact of body mass index (BMI) on the prognosis of patients with colorectal cancer remains largely unknown, particularly in Asian populations. Therefore, the aim of this study was to examine the influence of BMI on clinicopathological characteristics and mortality of Chinese colorectal cancer patients.MethodsThe study cohort consisted of 525 patients who were diagnosed with colorectal cancer and underwent radical surgery at the second hospital of Harbin Medical University between June 2004 and August 2011. Study participants were divided into two BMI categories: normal weight (BMI <23 kg/m2) and overweight (BMI ≥23 kg/m2).ResultsOf 525 patients, 208 patients (39.6%) were included in the normal-weight group and 317 patients were included in the overweight group. During the mean follow-up period of 48.8 months, 89 patients had disease recurrence and 131 deaths occurred. High BMI was significantly correlated with younger age, presence of diabetes, alcohol consumption, distal colon tumors, amount of lymph node harvested and pathological stage. No statistically significant correlation was found between high BMI and progression-free survival (PFS) or overall survival (OS) when the total group of patients was considered (P = 0.077 and P = 0.701, respectively). Cigarette-smoking patients had significantly shorter OS than patients who had never smoked (hazard ratio = 1.613, 95% confidence interval = 1.133 to 2.296; P = 0.008), and this difference in OS remained significant in multivariate analysis. Cigarette-smoking patients did not have significantly different PFS compared with patients who had never smoked.ConclusionThere was no significant correlation between obesity and outcomes of patients with colorectal cancer. In addition, our findings support the claims that cigarette smoking may be partially responsible for the divergent mortality of patients with colorectal cancer.

Relationship between tumor and peripheral blood NPRL2 mRNA levels in patients with colorectal adenoma and colorectal cancer

NPRL2 is a tumor suppressor gene involved in the progression of human cancer. The present study investigated whether NPRL2 expression correlates with colorectal cancer (CRC) progression. Colorectal tissue and peripheral blood samples were obtained from 62 patients with CRC, 38 patients with colorectal adenomas and 51 normal controls. NPRL2 mRNA levels in tissue samples and blood were measured using quantitative real-time PCR. NPRL2 protein expression was determined by immunohistochemistry. NPRL2 protein expression in CRCs was significantly lower than in the adenomas or normal colorectal tissue. NPRL2 mRNA expression was significantly decreased in adenomas compared with normal controls (P < 0.0001) and it was further decreased in colorectal tumors compared with adenomas (P < 0.0001). NPRL2 mRNA levels expression correlated with tumor stage. In addition, NPRL2 mRNA levels in the blood correlated with the levels detected in tumors. Furthermore, receiver operating characteristic (ROC) analysis showed that NPRL2 expression in blood could distinguish colorectal adenomas and CRCs from normal controls. NPRL2 mRNA expression in CRC tumor tissues and peripheral blood correlated with colorectal tumor progression. Based on our findings, we can conclude that NPRL2 mRNA blood levels could be a potentially useful marker for the detection of early stage adenomas and CRCs.

Esculin prevents Lipopolysaccharide/D-Galactosamine-induced acute liver injury in mice

Liver injury is an important cause of serious liver disease and is characterized by inflammatory and oxidative responses. Esculin, a coumarinic derivative found in Aesculus hippocastanum L., has been shown to exhibit anti-inflammatory and anti-oxidative effects. Here, we investigated the effects and molecular mechanism of esculin on Lipopolysaccharide/D-Galactosamine (LPS/D-Gal)-induced acute liver injury. A mouse model for acute liver injury was induced by intraperitoneal injection with D-Gal and LPS, and was assessed by histology, and serum transaminase analyses. The results showed that esculin significantly reduced the pathological symptoms of acute liver injury, as well as serum AST and ALT levels. LPS/D-Gal-induced liver myeloperoxidase (MPO) activity and malondialdehyde (MDA) content were also suppressed by esculin. Furthermore, LPS/D-Gal-induced liver tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production were attenuated by esculin. Our data demonstrate that esculin can inhibit nuclear factor kappa B (NF-κB) activation as well as increase nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. In conclusion, this paper demonstrates that esculin protects liver injury induced by LPS/D-Gal via inhibiting inflammatory and oxidative responses.