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Summary Androgen/androgen receptor (AR) signaling plays important roles in normal liver function and in progression of liver diseases. In studies of non-cancerous liver diseases, AR knockout mouse models of liver disease have revealed that androgen/AR signaling suppresses the development of steatosis, virus-related hepatitis, and cirrhosis. In addition, studies have shown that targeting AR in bone marrow-derived mesenchymal stem cells (BM-MSCs) improves their self-renewal and migration potentials, thereby increasing the efficacy of BM-MSC transplantation as a way to control the progression of cirrhosis. Androgen/AR signaling is known to be involved in the initiation of carcinogen- or Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, studies have demonstrated that AR, rather than androgen, plays the dominant role in cancer initiation. Therefore, targeting AR might be an appropriate therapy for patients with early-stage HCC. In contrast, androgen/AR signaling has been shown to suppress metastasis of HCC in patients with late-stage disease. In addition, there is evidence that therapy comprising Sorafenib and agents that enhance the functional expression of AR may suppress the progression of late-stage HCC.

Genetic variations in the COX2 and PLA2 genes increase the risk of IFN-alpha-induced depression, possibly by affecting the levels of EPA and DHA. Moreover, PLA2 genotype is associated with somatic symptoms in depression. Our study confirms the role of inflammatory mechanisms in major depression.

Human coronavirus NL63 (HCoV-NL63), one of the main circulating HCoVs worldwide, causes respiratory tract illnesses like runny nose, cough, bronchiolitis and pneumonia. Recently, a severe respiratory illness outbreak of HCoV-NL63 has been reported in a long-term care facility. Sambucus FormosanaNakai, a species of elderberry, is a traditional medicinal herb with anti-inflammatory and antiviral potential. The study investigated the antiviral activity of Sambucus FormosanaNakai stem ethanol extract and some phenolic acid constituents against HCoV-NL63. The extract was less cytotoxic and concentration-dependently increased anti-HCoV-NL63 activities, including cytopathicity, sub-G1 fraction, virus yield (IC50 = 1.17 μg/ml), plaque formation (IC50 = 4.67 μg/ml) and virus attachment (IC50 = 15.75 μg/ml). Among the phenolic acid constituents in Sambucus FormosanaNakai extract, caffeic acid, chlorogenic acid and gallic acid sustained the anti-HCoV-NL63 activity that was ranked in the following order of virus yield reduction: caffeic acid (IC 50 = 3.54 μM) > chlorogenic acid (IC 50 = 43.45 μM) > coumaric acid (IC 50 = 71.48 μM). Caffeic acid significantly inhibited the replication of HCoV-NL63 in a cell-type independent manner, and specifically blocked virus attachment (IC 50 = 8.1 μM). Therefore, the results revealed that Sambucus Formosana Nakai stem ethanol extract displayed the strong anti-HCoV-NL63 potential; caffeic acid could be the vital component with anti-HCoV-NL63 activity. The finding could be helpful for developing antivirals against HCoV-NL63.

BackgroundUntil now, no risk score could predict hepatocellular carcinoma (HCC) in nucleos(t)ide analog (NA)-treated Asian patients.MethodsWe enrolled 1325 NA-naïve chronic hepatitis B patients with entecavir monotherapy for >12 months, with 883 and 442 patients randomly assigned to the development and validation groups, respectively, in the risk model.ResultsThe cumulative probabilities of HCC were 2.4%, 4.1%, and 9.9% after 2, 3, and 5 years of treatment, respectively. In the development group, age, platelet counts, and alpha-fetoprotein levels after 12 months of treatment were the independent predictors of HCC. We converted the Cox proportional hazards regression coefficients for these predictors into risk scores and developed the APA-B model, with the total risk scores ranging from 0 to 15. The risk scores accurately categorized patients with low (0–5), medium (6–9), and high (10–15) risks in the validation group (P <0.001). The areas under the receiver operating characteristic curve for predicting HCC risk after 2, 3, and 5 years were 0.877, 0.842, and 0.827, respectively, in the development group and 0.939, 0.892, and 0.862, respectively, in the validation group.ConclusionThe proposed HCC risk prediction model exhibited excellent predictive accuracy in NA-naïve Asian patients receiving entecavir therapy.

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The objective of this study was to explore the association between statins use and risk of developing hepatocellular carcinoma (HCC). We used the research database of the Taiwan National Health Insurance program to conduct a population-based case-control study. Cases were 3,480 patients with newly diagnosed HCC identified during 2000 and 2009. Controls were 13,920 subjects without HCC and frequency matched for age, sex and duration of observational period of cases (i.e., the duration between year of being enrolled in the insurance program and index year of cases). Six commercially available statins, including simvastatin, lovastatin, fluvastatin, atorvastatin, pravastatin, and rosuvastatin, were analyzed. The adjusted odds ratio [OR] of HCC was 0.72 [95% (CI) 0.59-0.88] for the group with stains use, when compared to the group with non-use of statins. In sub-analysis, simvastatin (OR 0.69, 95% CI 0.50-0.94), lovastatin (OR 0.52, 95% CI 0.36-0.76) and atorvastatin (OR 0.70, 95% CI 0.53-0.93) were associated with significant reduction in odds of HCC. Statins use correlates with 28% decreased risk of HCC. Individual statins, including simvastatin, lovastatin and atorvastatin, are associated with reduced risk of HCC.