Ling Xu

Rifaximin versus Nonabsorbable Disaccharides for the Treatment of Hepatic Encephalopathy: A Meta-Analysis

Background. Many studies have found that the antibiotic rifaximin is effective for the treatment of hepatic encephalopathy. However, there is no uniform view on the efficacy and safety of rifaximin. Methods. We performed a meta-analysis through electronic searches to evaluate the efficacy and safety of rifaximin in comparison with nonabsorbable disaccharides. Results. A total of 8 randomized controlled trials including 407 patients were included. The efficacy of rifaximin was equivalent to nonabsorbable disaccharides according to the statistical data (risk ratio (RR): 1.06, 95% CI: 0.94–1.19; P = 0.34). Analysis showed that patients treated with rifaximin had better results in serum ammonia levels (weighted mean difference (WMD): −10.63, 95% CI: −30.63–9.38; P = 0.30), mental status (WMD: −0.32, 95% CI: −0.67–0.03; P = 0.07), asterixis (WMD: −0.12, 95% CI: −0.31–0.08; P = 0.23), electroencephalogram response (WMD: −0.21, 95% CI: −0.34–−0.09; P = 0.0007), and grades of portosystemic encephalopathy (WMD: −2.30, 95% CI: −2.78–−1.82; P < 0.00001), but only the last ones had statistical significance. The safety of rifaximin was better than nonabsorbable disaccharides (RR: 0.19, 95% CI: 0.10–0.34; P < 0.00001). Conclusion. Rifaximin is at least as effective as nonabsorbable disaccharides, maybe better for the treatment of hepatic encephalopathy. And the safety of rifaximin is better.

Combination Therapy of Ursodeoxycholic Acid and Corticosteroids for Primary Biliary Cirrhosis with Features of Autoimmune Hepatitis: A Meta-Analysis

A meta-analysis was performed of RCTs comparing therapies that combine UDCA and corticosteroids with UDCA monotherapy. In this paper, we found that the combination therapy of UDCA and corticosteroids was more effective for PBC-AIH.

Diagnostic Performance of Des-γ-carboxy Prothrombin for Hepatocellular Carcinoma: A Meta-Analysis.

Background. There have been many reports on des-γ-carboxy prothrombin (DCP) as a promising serum marker in the diagnosis of hepatocellular carcinoma (HCC); however, the results are inconsistent and even conflicting. Methods. This meta-analysis was performed to investigate the performance of DCP in the diagnosis of HCC. Following a systematic review of relevant studies, Meta-DiSc 1.4 software was used to extract data and to calculate the overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Data are presented as forest plots and summary receiver operating characteristic curve (SROC) analysis was used to summarize the overall test performance. Results. Twelve studies were included in our meta-analysis. The overall sensitivity, specificity, PLR, and NLR of DCP for the detection of HCC in the studies included were 71% (95%CI: 68%–73%), 84% (95%CI: 83%–86%), 6.48 (95%CI: 4.22–9.93), and 0.33 (95%CI: 0.25–0.43), respectively. The area under the SROC curve was 0.8930 and the Q index was 0.8238. Significant heterogeneity was found. Conclusion. This meta-analysis indicated that DCP had moderate diagnostic accuracy in HCC. Further studies with rigorous design, large sample size, and mmultiregional cooperation are needed in the future.

The long noncoding RNA TUG1 acts as a competing endogenous RNA to regulate the Hedgehog pathway by targeting miR-132 in hepatocellular carcinoma

Emerging evidence shows that the Hedgehog pathway and the long noncoding RNA TUG1 play pivotal roles in cell proliferation, migration, and invasion in tumors. However, the mechanism underlying the effect of TUG1 and the Hedgehog pathway in hepatoma remains undefined. In the present study, we showed that the expression of TUG1 was negatively correlated with that of microRNA (miR)-132, and depletion of TUG1 inhibited the activation of the Hedgehog pathway in vitro and in vivo. We showed that TUG1 functions as a competing endogenous (ceRNA) by competing with miR-132 for binding to the sonic hedgehog protein in HCC, thereby suppressing the activation of Hedgehog signaling and its tumorigenic effect. These data indicate that targeting the TUG1-miR132-Hedgehog network could be a new strategy for the treatment of HCC.

Modified Sequential Therapy Regimen versus Conventional Triple Therapy for Helicobacter pylori Eradication in Duodenal Ulcer Patients in China: A Multicenter Clinical Comparative Study

Objective. Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. To observe the effect of eradicating Helicobacter pylori (H. pylori) and the treatment of duodenal ulcer by 2 kinds of modified sequential therapy through comparing with that of 10-day standard triple therapy. Methods. A total of 210 patients who were confirmed in duodenal ulcer active or heal period by gastroscopy and H. pylori positive confirmed by rapid urease test, serum anti-H. pylori antibody (ELASE), or histological examination enrolled in the study. All the patients were randomly divided into three groups: group A (70 cases) and group B (70 cases) were provided 10-day modified sequential therapy; group C (70 cases) was provided 10-day standard triple therapy. Patients of group A received 20u2009mg of Esomeprazole, 500u2009mg of Clarithromycin for the first 5 days, followed by 20u2009mg of Esomeprazole, 500u2009mg of Clarithromycin, and 1000u2009mg of Amoxicillin for the remaining 5 days. Group B received 20u2009mg of Esomeprazole, 1000u2009mg of Amoxicillin for the first 5 days, followed by 20u2009mg of Esomeprazole, 500u2009mg of Clarithromycin, and 1000u2009mg of Amoxicillin for the remaining 5 days. Group C received 20u2009mg of Esomeprazole, 500u2009mg of Clarithromycin, and 1000u2009mg of Amoxicillin for standard 10-day therapy. All drugs were given twice daily. H. pylori eradication rate was checked four to eight weeks after taking the medicine by using a 13C urea breath test. In the first, second, third, seventh, twenty-first, thirty-fifth days respectively, the symptoms of patients such as epigastric gnawing, burning pain, and acidity were evaluated simultaneously. Results. Overall, 210 patients accomplished all therapy schemes, 9 case patients were excluded. The examination result indicated that the H. pylori eradication rate of each group was as follows: group A 92.5% (62/67), group B 86.8% (59/68), and group C 78.8% (52/66). The H. pylori eradication rate of group A was slightly higher than group B (P < 0.05) and both of them were obviously higher than group C (P < 0.05). Modified sequential therapy was significantly more effective in patients with clarithromycin-resistant strains (80%/67% versus 31%; P = 0.02). Symptoms improvement: all the three groups could improve the symptoms such as epigastric gnawing, burning pain, and acidity since the first day. There was no significant difference in total score descending of symptoms between each group (P > 0.05). Conclusions. All the three therapy schemes could alleviate symptoms of duodenal ulcer patients in China efficiently. But as far as eradicating H. pylori is concerned, the modified sequential therapy was better than standard triple therapy, especially the therapy scheme used in group A.

Methylation-regulated miR-124-1 suppresses tumorigenesis in hepatocellular carcinoma by targeting CASC3

This study was to investigate the roles and mechanisms of miR-124-1 in hepatocellular carcinoma (HCC). We analyzed the expression of miR-124-1 in human HCC tissues and cell lines. Luciferase reporter assays were used to analyze the target of miR-124-1. Human HCC cell lines were transduced with lentiviruses expressing miR-124-1, and proliferation and colony formation were analyzed. The growth of human HCC cells overexpressing miR-124-1 was assessed in nude mice. The expression of p38-MAPK, JNK, ERK and related signaling molecules was detected by western blotting and immunohistochemistry. Our results showed that miR-124-1 levels were reduced in HCC tissues and cell lines compared with those in adjacent non-cancer tissues and normal liver cell lines respectively. Downregulation of miR-124-1 in HCC cell lines were attributed to hypermethylation of its promoter region. Overexpression of miR-124-1 inhibited HCC cell proliferation in vitro, whereas miR-124-1 was correlated with clinicopathological parameters of HCC patients. HCC cell-mediated overexpression of miR-124-1 in nude mice suppressed tumor growth. Cancer susceptibility candidate 3 (CASC3) was identified as a direct target of miR-124-1 by computational analysis and experimental assays. MiR-124-1-mediated downregulation of CASC3 resulted in the inactivation of p38-MAPK, JNK and ERK. Our findings provide potential new targets for the prevention or treatment of HCC.

The inhibitory effects of xanthohumol, a prenylated chalcone derived from hops, on cell growth and tumorigenesis in human pancreatic cancer.

Pancreatic cancer (PC) is one of the most lethal human malignancies worldwide. Here, we demonstrated that xanthohumol (XN), the most abundant prenylated chalcone isolated from hops, inhibited the growth of cultured PC cells and their subcutaneous xenograft tumors. XN treatment was found to induce cell cycle arrest and apoptosis of PC cells (PANC-1, BxPC-3) by inhibiting phosphorylation of signal transducer and activator of transcription 3 (STAT3) and expression of its downstream targeted genes cyclinD1, survivin, and Bcl-xL at the messenger RNA level, which involved in regulation of apoptosis and the cell cycle. Overall, our results suggested that XN presents a promising candidate therapeutic agent against human PC and the STAT3 signaling pathway is its key molecular target.

Methyl jasmonate leads to necrosis and apoptosis in hepatocellular carcinoma cells via inhibition of glycolysis and represses tumor growth in mice

Methyl jasmonate has recently been found to have anti-cancer activity. Methyl jasmonate detached hexokinase 2 from a voltage dependent anion channel causing a reduction in mitochondrial transmembrane potential that led to the release of cytochrome C and apoptosis inducing factor resulting in intrinsic apoptosis. Blocked adenosine triphosphate synthesis caused by mitochondrial injury hampered oxidative phosphorylation and led to cell necrosis. The results were applied to the in vivo treatment of nude mice with a satisfactory effect. Collectively, our results suggest that methyl jasmonate may be an adjuvant therapy for liver tumors due to its mechanism in cancer cells compared to that in normal cells: The major function is to inhibit glycolysis instead of changing aerobic metabolism.

Fucosterol Protects against Concanavalin A-Induced Acute Liver Injury: Focus on P38 MAPK/NF-κB Pathway Activity

Objective Fucosterol is derived from the brown alga Eisenia bicyclis and has various biological activities, including antioxidant, anticancer, and antidiabetic properties. The aim of this study was to investigate the protective effects of fucosterol pretreatment on Concanavalin A- (ConA-) induced acute liver injury in mice, and to understand its molecular mechanisms. Materials and Methods Acute liver injury was induced in BALB/c mice by ConA (25u2009mg/kg), and fucosterol (dissolved in 2% DMSO) was orally administered daily at doses of 25, 50, and 100u2009mg/kg. The levels of hepatic necrosis, apoptosis, and autophagy associated with inflammatory cytokines were measured at 2, 8, and 24u2009h. Results Fucosterol attenuated serum liver enzyme levels and hepatic necrosis and apoptosis induced by TNF-α, IL-6, and IL-1β. Fucosterol also inhibited apoptosis and autophagy by upregulating Bcl-2, which decreased levels of functional Bax and Beclin-1. Furthermore, reduced P38 MAPK and NF-κB signaling were accompanied by PPARγ activation. Conclusion This study showed that fucosterol could alleviate acute liver injury induced by ConA by inhibiting P38 MAPK/PPARγ/NF-κB signaling. These findings highlight that fucosterol is a promising potential therapeutic agent for acute liver injury.

Isorhamnetin: A hepatoprotective flavonoid inhibits apoptosis and autophagy via P38/PPAR-α pathway in mice

Isorhamnetin, a flavonoid compound extracted from plants fruit or leaves, like sea buckthorn (Hippophae rhamnoides L.), has many biological functions, including anti-tumor, anti-oxidant and anti-inflammatory effect. The present study is in order to explore the hepatoprotective effect of isorhamnetin on concanavalin A (ConA)-induced acute fulminant hepatitis and the underlying mechanism. Mice were injected with ConA (25u202fmg/kg) to induce acute fulminant hepatitis, three doses of isorhamnetin (10/30/90u202fmg/kg) was intraperitoneally administrated about 1u202fh previously. The serum and liver tissues were harvested at 2, 8, and 24u202fh after ConA injection. The levels of serum liver enzymes and proinflammatory cytokines were significantly reduced in isorhamnetin administration groups. Besides, isorhamnetin improved pathological damage. Furthermore, isorhamnetin affected P38/PPAR-α pathway, and subsequently regulated the expression of apoptosis and autophagy related proteins. The present study investigated that isorhamnetin inhibits apoptosis and autophagy via P38/PPAR-α pathway in mice.