Background: Hepatocellular carcinoma (HCC) is a frequently diagnosed cancer and a leading cause of cancer-related death worldwide. Its rapid progression, combined with the limited treatment options at late stages, imposes the need for early detection and aggressive intervention. Based on the knowledge that hepatocarcinogenesis is significantly influenced by histone acetylation, we directed our search for novel HCC therapeutics among histone deacetylation inhibitors (HDACi). The aim of the present study was to investigate the effect of HDAC1/2 inhibitor Romidepsin in the well-established mouse model of diethylnitrosamine (DEN)-induced HCC. Materials and Methods: C56BL/6 mice were treated with Romidepsin at the critical point of 10 months after DEN challenge and their livers were examined 2 months later using histopathology and morphometry. Protein levels were assessed in serum using ELISA and in liver tissues using Western blot and immunohistochemistry (in-situ detection). Gene expression was quantified using real-time PCR. Results: Romidepsin suppressed cancer progression. This effect was associated with decreased proliferation and increased apoptosis of cancer cells. The cell cycle regulator CK2a, the anti-inflammatory molecule PPAR-γ, and the tumor suppressors PTEN and CYLD were upregulated in treated HCC. By contrast, the expression of PI3K, NF-κB p65 and c-Jun was reduced. In line with this result, the levels of two major apoptosis regulators, ie, BAD and the multifunctional protein c-Met, were lower in the blood serum of treated mice compared to the untreated mice with HCC. Conclusion: These findings suggest that Romidepsin, a drug currently used in the treatment of lymphoma, could also be considered in the management of early-stage HCC.

Neutrophil and T-cell recruitment contribute to hepatic ischemia/reperfusion injury. The initial inflammatory response is orchestrated by Kupffer cells and liver sinusoid endothelial cells. However, other cell types, including γδ-Τ cells, seem to be key mediators in further inflammatory cell recruitment and proinflammatory cytokine release, including IL17a. In this study, we used an in vivo model of partial hepatic ischemia/reperfusion injury (IRI) to investigate the role of the γδ-Τ-cell receptor (γδTcR) and the role of IL17a in the pathogenesis of liver injury. Forty C57BL6 mice were subjected to 60 min of ischemia followed by 6 h of reperfusion (RN 6339/2/2016). Pretreatment with either anti-γδΤcR antibodies or anti-IL17a antibodies resulted in a reduction in histological and biochemical markers of liver injury as well as neutrophil and T-cell infiltration, inflammatory cytokine production and the downregulation of c-Jun and NF-κΒ. Overall, neutralizing either γδTcR or IL17a seems to have a protective role in liver IRI.

The impact of dietary inclusion of Spirulina platensis on the immune system, intestinal microbiome and skin of mink was investigated. Forty-eight animals were equally separated into four groups. Groups B and D were control animals, while groups A and C had their feed supplemented daily with 100 mg/kg of body weight Spirulina. Mink in groups A and B were descended from dams supplemented with spirulina during their reproductive period, while those in groups C and D were descended from dams fed the control diets. Fur growth rate and quality were graded semi-quantitatively. Fecal microbiome analysis, skin thickness histomorphometry, immunohistochemical labeling and counts of immune cells in the colon, mesenteric lymph nodes and spleen and quantitative gene expression analysis of cytokines in the colon were performed. Skin thickness, fur growth rate and skin quality were similar among groups (p > 0.05). However, differences were observed among groups concerning the relative and differential abundance of bacterial species. Tgf-β expression was lower in group A, whereas IL-β1 was lower in group C compared to group B (p < 0.05). Group D had significantly lower numbers of inflammatory cells in the colon and mesenteric lymph nodes. The results revealed that Spirulina decreased indices of subclinical inflammation in mink gut, while differences in the bacterial communities among groups were observed.