Activity

Chromatin immunoprecipitation (ChIP) analysis proved HIF-1 ability to bind to the promoter region of PEPCK-C gene. The final conclusion that hypoxia/HIF-1 accelerates the rate of renal glucogenesis via the mechanism engaging activation of PEPCK-C expression might be useful in terms of e.g. diabetes treatment, as it is commonly accepted that under diabetic conditions kidneys and liver seem to be equally important sources of glucose synthesized de novo. V.Hepatotoxicity is among the most frequent reasons for drug withdrawal from the market. Therefore, there is an urgent need for reliable predictive in vitro tests, which unfailingly identify hepatotoxic drug candidates, reduce drug development time, expenses and the number of test animals. Currently, human hepatocytes represent the gold standard. However, the use of hepatocytes is challenging since the cells are not constantly available and lose their metabolic activity in culture. To solve these problems many different approaches have been developed in the past decades. The aim of this review is to present these approaches and to discuss the possibilities and limitations as well as future opportunities and directions. Juglans regia L. (walnut) green husks are an important fraction of waste resulting from the walnut production, thus representing an interesting natural matrix to explore as a source of bioactive compounds. In this work, the hydroethanolic extract of walnut green husks was studied considering the phytochemical composition and the biological activity using different cell model assays, most of them evaluated for the first time for this matrix. selleck products From the HPLC-DAD-ESI/MSn analysis, sixteen compounds were identified, being the extract mostly composed of naphthalene derivatives (including tetralone derivatives) and less abundant in phenolic compounds (hydroxycinnamic acids and flavonols). The cytotoxic potential of the extract was assessed against tumour (MCF-7, NCI-H460, HeLa and HepG2) and non-tumour (PLP2) cell lines. Moreover, the antioxidant activity of the extract was evaluated by inhibition of the oxidative haemolysis (OxHLIA) and the formation of thiobarbituric acid reactive substances (TBARS), and the anti-inflammatory potential by the inhibition of the NO production by the RAW264.7 cell culture. The antibacterial effects of the extract were also evaluated against Gram-negative and Gram-positive bacteria. The results obtained represent a stepping stone for the development of future applications using walnut green husks as a source of added value compounds with bioactive potential. Liver regenerates following surgical removal and after drug-induced liver injury (DILI). However, most of the mechanisms of liver regeneration were identified using partial hepatectomy (PHX) model rather than using DILI models. We compared mechanisms of liver regeneration following PHX and after acetaminophen (APAP) overdose, a DILI model, using transcriptomic approach. Kinetics of hepatocyte proliferation and global gene expression profiles were studied in male C57BL/6J mice either subjected to PHX or following APAP overdose. Liver regeneration was much more synchronized after PHX as compared to APAP overdose. Transcriptomics analysis revealed activation of common upstream regulators in both models including growth factors HGF, EGF and VEGF; and cytokines IL6 and TNFα. However, magnitude of activation and temporality was significantly differed between the two models. HGF and VEGF showed similar activation between PHX and APAP but activation of EGF was significantly stronger in the APAP model. Activation of IL6 and TNFα transcriptional programs was delayed but remarkably higher in APAP. These dissimilarities could be attributed to inherent differences in the two models including significant injury and inflammation exclusively in the APAP model. This study highlights need to study mechanisms of liver regeneration after DILI separately from the mechanisms of regeneration PHX. There are significant differences between different Nocardia species regarding geographical distribution, biochemical features, phenotypic characterization, and drug sensitivity. In this study, we explored the differences in virulence and pathogenic mechanisms of two Nocardia cyriacigeorgica strains. We examined the difference in virulence between N. cyriacigeorgica ATCC14759 and N. cyriacigeorgica GUH-2 by measuring cytotoxicity, animal survival after infection, the ability of host cell invasion, and viability in host cells. Western blotting was used to compare the differences in activation of MAPKs, including p38, ERK, and JNK, the NF-κB signaling pathway, and the PI3K/Akt signaling pathway in A549 and RAW264.7 cells. We measured the difference in stimulatory effects on production of the cytokines IL-6, IL-10, and TNF-α by ELISA. We found that N. cyriacigeorgica ATCC14759 causes higher cytotoxicity in cultured cells and higher lethality in mice, and exhibits superior invasion ability and viability in host cells compared with N. cyriacigeorgica GUH-2. Moreover, these two strains show marked differences in activation of the expression of cytokines and signaling pathways. N. cyriacigeorgica ATCC14759 is more virulent than N. cyriacigeorgica GUH-2. Furthermore, there is a significant difference in pathogenesis between the two strains. Our results provide a theoretical basis for the prevention and treatment of Nocardia infection. Human colorectal cancer is the third most common cancer around the world. Colorectal cancer has various risk factors, but current works have bolded a significant activity for the microbiota of the human colon in the development of this disease. Bacterial biofilm has been mediated to non-malignant pathologies like inflammatory bowel disease but has not been fully documented in the setting of colorectal cancer. The investigation has currently found that bacterial biofilm is mediated to colon cancer in the human and linked to the location of human cancer, with almost all right-sided adenomas of colon cancers possessing bacterial biofilm, whilst left-sided cancer is rarely biofilm positive. The profound comprehension of the changes in colorectal cancer can provide interesting novel concepts for anticancer treatments. In this review, we will summarize and examine the new knowledge about the links between colorectal cancer and bacterial biofilm.