Matrix metalloproteinases (MMPs) are known to play important roles in extracellular matrix remodeling during the process of tumor invasion and metastasis. However, little is known about their role in esophageal squamous cell carcinoma (ESCC). Expression of MMP-2 and MMP-9 in ESCC was detected in our research. Tissue microarray chip was prepared, consisting of 58 cases of ESCC and corresponding esophageal epithelium tissues. MMP-2 and MMP-9 were examined by immunohistochemistry. Overexpression of MMP-2 and MMP-9 was found in ESCC (42.1 and 60.3%, respectively), compared with paired distal normal esophageal tissues (22.9 and 8.9%, respectively). Expression of MMP-2 in ESCC was significantly associated with the tumor invasion depth, tumor-node-metastasis stages, and lymph node metastasis. MMP-2 and MMP-9 may play important roles in carcinogenesis, and MMP-2 may act as a biological marker of invasion and lymph node metastasis in ESCC.

h Hepatitis B virus (HBV) remains a major human pathogen despite the development of both antiviral drugs and a vaccine, in part because the current therapies do not suppress HBV replication far enough to eradicate the virus. Here, we screened 51 troponoid compounds for their ability to suppress HBV RNaseH activity and HBV replication based on the activities of ␣-hydroxytropolones against HIV RNaseH, with the goal of determining whether the tropolone pharmacophore may be a promising scaffold for anti-HBV drug development. Thirteen compounds inhibited HBV RNaseH, with the best 50% inhibitory concentration (IC 50 ) being 2.3 M. Similar inhibition patterns were observed against HBV genotype D and C RNaseHs, implying limited genotype specificity. Six of 10 compounds tested against HBV replication in culture suppressed replication via blocking of viral RNaseH activity, with the best 50% effective concentration (EC 50 ) being 0.34 M. Eighteen compounds inhibited recombinant human RNaseH1, and moderate cytotoxicity was observed for all compounds (50% cytotoxic concentration [CC 50 ] ‫؍‬ 25 to 79 M). Therapeutic indexes ranged from 3.8 to 94. Efficient inhibition required an intact ␣-hydroxytropolone moiety plus one or more short appendages on the tropolone ring, but a wide variety of constituents were permissible. These data indicate that troponoids and specifically ␣-hydroxytropolones are promising lead candidates for development as anti-HBV drugs, providing that toxicity can be minimized. Potential anti-RNaseH drugs are envisioned to be employed in combination with the existing nucleos(t)ide analogs to suppress HBV replication far enough to block genomic maintenance, with the goal of eradicating infection. More than 2 billion people have been infected with hepatitis B virus (HBV) at some time in their lives and up to 350 million remain chronically infected as carriers of HBV (1, 2). Approximately 20% of chronic hepatitis B patients develop liver cirrhosis, leading to hepatic insufficiency and portal hypertension (3). Furthermore, there is a 100-fold higher risk of development of hepatocellular carcinoma in chronic HBV patients than in noncarriers (4). Every year, HBV infection kills more than 500,000 people from cirrhosis, liver failure, and hepatocellular carcinoma (5).The global level of chronic HBV infection still mandates development of new drugs despite the development of excellent vaccines and drugs against the virus. Seven drugs have been approved by the U.S. Food and Drug Administration for treating HBV infection. Interferon alpha and pegylated interferon alpha are immunomodulatory agents. However, the need for subcutaneous administration, the poor long-term responses, the very low cure rates, and the high frequency of adverse side effects make interferon far from an ideal drug (6). The nucleos(t)ide analog drugs lamivudine, adefovir, entecavir, telbivudine, and tenofovir are phosphorylated to their triphosphate derivatives by cellular enzymes and become chain-terminating substrates of the HBV reverse transcr...

Oral administration of Bifidobacteria has the capacity to suppress the skewed Th2 response in allergic mice, increasing the number of Treg and IL-10-positive cells and improve the impaired intestinal epithelial barrier function.

ARK5 overexpression has been reported in a variety of human cancers. However, the role of ARK5 in hepatocellular carcinoma (HCC) remains unclear. The aim of the present study is to analyze the ARK5 protein expression in HCC tissue samples and to assess its prognostic significance for HCC. ARK5 mRNA and protein expression were determined by real-time quantitative reverse transcriptase-polymerase chain reaction and Western blot in 20 pairs of fresh frozen HCC tissues and corresponding non-cancerous tissues. In addition, ARK5 expression was analyzed by immunohistochemistry in 130 clinicopathologically characterized HCC cases. The correlation of ARK5 expression with patients' survival rate was assessed by Kaplan-Meier and Cox regression. Our results showed that the expression levels of ARK5 mRNA and protein in HCC tissues were both significantly higher than those in non-cancerous tissues. Our results showed that the high expression of ARK5 in HCC was related to tumor size (p=0.005), histological differentiation (p=0.047), and tumor stage (p=0.005). Kaplan-Meier survival analysis showed that a high expression level of ARK5 resulted in a significantly poor prognosis of HCC patients. Multivariate analysis revealed that ARK5 expression level was an independent prognostic parameter for the overall survival rate of HCC patients. In conclusion, ARK5 might play a positive role in tumor development and could serve as an independent predictor of poor prognosis for HCC.