Carcinoma, Hepatocellular ; genetics ; Gene Expression ; Humans ; Liver Neoplasms ; genetics

Liver regeneration depends on powerful immune system of ownself. TNF-α,IFN-γ,IL-6,IL-12,etc. that secreted by innate immune cells such as macrophages,dendritic cells,NK cells and NKT cells,could act on the hepatocytes and regulate liver regen-eration (LR) through corresponding signaling pathways. This article summarizes the mechanism of different innate immune cells on hep-atocytes,clarifies the recent advances of liver innate immune cellsduring liver regeneration process,lay the foundation for revealing the molecular mechanism of the development of liver regeneration and liver diseases, and for the research and development of new therapeutic methods for liver diseases.

Objective To investigate the regulation of liver regeneration (LR) by changes in energy metabolites in the initiation phase during rat liver regeneration. Methods Rats were randomly divided into 3 groups with 5 rats in each group, including two partial hepatectomy (PH) groups and one normal control group. Selective reaction monitoring/multiple reaction monitoring (SRM/MRM) was employed in the targeted metabolomics identification of 29 energy metabolites. Ingenuity Pathway Analysis (IPA) was applied for integration analysis, including canonical pathway and molecular interaction network. Results The levels of 3-phospho-D-glycerate, AMP, cyclic AMP, D-fructose 1, 6-bisphosphate, dihydroxyacetome phosphate (DHAP), guanosine monophosphate (GMP), guanosine triphosphate (GTP), nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinueleotide phosphate ( NADP ) significantly increased. The levels of alpha-ketoglutarate, beta-D-fructose 6-phosphate, cis-aconitate, D-glucose 6-phosphate, lactate, NADPH, oxaloacetate and pyruvate dramatically reduced. Through hierarchical clustering analysis of energy metabolisms, these energy metabolisms can be grouped into four clusters. IPA showed that the biomolecular changes in the priming phase of liver regeneration are mainly related to carbohydrate metabolism, cellular growth and proliferation, and organismal development. During the priming phase of liver regeneration, adenosine 5'-monphosphate-activated protein kinase (AMPK), hypoxia- inducible factor la (HIF-la), peroxisome proliferator-activated receptor (PPAR), protein kinase A (PKA) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways are involved in energy metabolism, and glycolysis may be the main mode of energy supply. Conclusion The result suggests that the changes of energy matabolites during the initial stage of LR play a regulatory role in live regeneration.

Objective To explore the regulation of amino acid metabolism during rat liver regeneration (LR). Methods Rats were randomly divided into 10 groups with 5 rats in each group, including nine partial hepatectomy (PH) groups and one normal control group. Selective reaction monitoring/multi reaction monitoring (SRM/MRM) was employed in the targeted metabolomics identification of 20 amino acids at 10 time points in rat liver regeneration. The change of amino acid content was analyzed by hierarchical clustering. Results Alanine was up-regulated at 30, 36 and 72 hours ; arginine was up-regulated at 6 and 12 hours; aspartic acid was up-regulated at 6, 12 and 36 hours; glutamate was up-regulated at 6, 12, 30, 36, 72 and 120 hours; histidine was up-regulated at 12, 24, 30, 36, 72 and 120 hours; glutamine was up- regulated at 72 hours, and isoleucine was down-regulated at 24 hours. Through hierarchical clustering analysis of amino acids, these amino acids can be grouped into three clusters. Conclusion Many amino acids have changed during the liver regeneration, and throughout the whole process of rat liver regeneration. Changes in amino acids content play an important role in hepatocyte proliferation during the liver regeneration.

MicroRNAs (miRNAs, miR) are endogenous non-coding single-stranded RNAs with a length of about 22 nucleotides. These RNAs play an important biological function within cells, among which, miR-429 has been proved to play an important role in inhibiting tumor development and tumor progression as well as in cell differentiation and neurological diseases by regulating the expression of different target genes. In this paper, the role of miR-429 and its downstream targeted genes in cell proliferation, apoptosis, migration and invasion is summarized.

Objective To explore the pathways and patterns which the CCAAT enhancer binding protein δ (CEBPδ) mRNA, miR-3553 and rno-Acad8_0002 regulate the hepatocytes in G

Objective To explore the pathways and patterns which CCAAT enhancer binding proteina (CEBPα) mRNA, miR-144-3p, rno-LOC100365958_0001, rno-Usp3_0010 and rno-AC241873_0010 regulate the hepatocytes in G

Objective To explore the pathways and patterns which CCAAT/enhancer binding protein β(CEBPβ) mRNA, miR-369-3p and rno-Rmdn2_0006 regulate the hepatocytes in G

Objective To explore the pathways and patterns which the CCAAT enhancer binding protein ζ (CEBPO mRNA, miR-136-3p, rno-Crebrf_0009, rno-Slc38a9_0001, rno-LOCl00362999_0001 and rno- Got1_0001 regulate the hepatocytes in G

Objective This study aims to investigate the expression profile and regulatory effect on cell proliferation of circular RNA(circRNA) in rat liver regeneration (LR). Methods CircRNA expression profile during rat LR of 114 rats ' regenerating liver which induced by 2/3 partial hepatectomy was detected by high-throughput sequencing. MiRanda and TargetScan were performed to predict their target microRNA (miRNAs) and mRNAs. Gene Ontology (GO) and IP A were used to analyze the physiological activities and signaling pathways they involved. Cytoscape v3. 0. 2 was used to construct the interaction network. Finally, the candidate key circRNAs were selected by the expression pattern combining with the number and function of target miRNAs. Results 20 878 circRNAs were detected during rat LR, among which 560 of them were differentially expressed, and 126 of them could bind to 117 target miRNAs, which were in turn to regulate 6510 downstream target mRNAs. They were involved in cell proliferation, stress response, substance metabolism and transforming growth factor-β (TGF-β), protein kinase A (PKA), Wnt/beta-catenin signaling pathways. 6 differential expressed circRNAs, including circRNA_03651, circRNA_03653, circRNA_04500, circRNA_05865, circRNA_l 1274 and circRNA_ 13559 might play a pivotal role in cell proliferation involved in rat LR by regulating 12 miRNAs and 15 mRNAs. Resultsing they were regarded as the candidate key circRNAs of rat LR. Conclusion 560 circRNAs were differentially expressed in rat LR, among which circRNA_03651, circRNA_03653, circRNA_04500, circRNA_05865, circRNA_l 1274 and circRNA_13559 might play a crucial role on cell proliferation involved in rat LR via 12 miRNAs-15 mRNAs axis.