Objective: To examine the effects of RS on serum cholesterol and expression of genes associated with cholesterol metabolism in rat liver for understanding its mechanism. Method: Eighteen rats were randomly assigned to three groups, six rats each. They were fed with chemical purified normal diet (control group), low RS (15%Hi-maize 1043) diet and high RS (30%Hi-maize 1043) diet respectively. Six weeks later, serum cholesterol and short chain fatty acid (SCFA) in the cecum were measured. Likewise, hepatic cholesterol 7?-hydroxylase, LDL receptor, and SR-B1 mRNA levels were measured by realtime PCR. Results: Hepatic cholesterol 7a-hydroxylase, LDL receptor, SR-B1 mRNA levels and cecal acetate, propionate and n-butyrate concentrations in the high RS group were significantly higher than those in the control group (P

Objective To investigate the role of mesenchymal stem cells in the repair of radiation induced liver injury.Methods 12 female SD rats were irradiated with 20 Gy 6 MV X-rays on the right lobe of the liver,to establish the model of radiation induced liver injury.The rats were divided randomly into two groups as invention group and control group,and transplanted with 1 ml male mesenchymal suspension or 1 ml normal saline in 4 hours after radiotherapy.The morphological changes of liver were observed.The existence of sex determining gene Y(SRY)and the level of alpha-smooth muscle actin (a-SMA) were detected.Results Some injury of right lobe liver in two groups were observed,and the injury degree of right lobe liver in intervention group were lower than that of control group.The amount of SRY positive cells in the right lobe liver of intervention group was higher than that in the left lobe liver(t ＝ 3.77,P ＜0.05).The positive expression rate of a-SMA in right lobe liver of intervention group was lower than that of control group.Conclusions Acute radiation induced liver injury could lead BMSCs＇ homing in order to decrease the degree of liver fibrosis.

Phosphodiesterases(PDE)are involved in the regulation of cellular physiological processes and neurological functions,including neuronal plasticity,synapto-genesis,synaptic transmission,memory formation and cognitive functions by catalyzing the hydrolysis of intracellular cyclic adenosine monophosphate(cAMP)and cyclic guanosine monophosphate(cGMP).Many basic and clinical studies have shown that PDE4 inhibitors block or ameliorate the occurrence and development of central nervous system(CNS)diseases by inhibiting cAMP hydrolysis,increasing cAMP content and enhancing its downstream effects.PDE4 inhibitors have long-term potentiation effect,which can enhance phosphorylation of cAMP response element binding protein(CREB)and upregulate expression of memory related Arc genes in hippocampal neurons,thereby improving cognitive impairment and Alzheimer's disease-like symptoms.They can also delay the occurrence and development of Parkinson's disease by reducing the cytotoxicity induced by α-syn and increasing the effect of miR-124-3p on cell functions.Alteration of PDE4 activity is the molecular basis for psychosis and some cognitive disorders,therefore it is considered as a therapeutic target for schizophrenia.PDE4 inhibitors play a role in depression by inhibiting the advanced glycation end product receptor(RAGE),TLR4 and NLRP3 pathways in the hippocampus,reducing the activation of microglia and the production of IL-1β,down-regulating HMGB1/RAGE signaling pathway and inhibiting inflammatory factors.PDE4 inhibitor plays a role in the treatment of autism spectrum disorder by reducing the damage of cerebellar glial cells,increasing nociceptive threshold,and improving mutual learning and memory deficits.PDE4 inhibitors might be used in the treatment of fragile X syndrome by regulating the level of cAMP and affecting the expression of fragile X mental retardation protein(FMRP).PDE4 inhibitors can also promote the differentiation of oligodendrocyte progenitor cells and enhance myelination,which has potential in the treatment of multiple sclerosis.PDE4 is also related to bipolar disorder,which may be one of the therapeutic targets.At present,several PDE4 inhibitors are in clinical trials for the treatment of CNS diseases.This article reviews and discusses the progress on basic research and clinical trials of PDE4 inhibitors in CNS diseases,providing a reference for the prevention and treatment of CNS diseases and the development of new drugs.

Objective : To investigate the mechanism of miRNAs in glycyrrhizic acid treatment of alcohol⁃induced liver injury in rats . Methods : 45 male SD rats were randomly divided into glycyrrhizin group , model group and control group . The rats in glycyrrhizin group were given 56% liquor and glycyrrhizin , the rats in model group were given 56% liquor , and the rats in control group were given distilled water for 8 weeks . The blood was collected and the serum was separated by centrifugation to detect the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) . RNA were extracted from liver tissues , miRNAs were detected by rat miRNA microarray , and their expression levels were analyzed . The miRNA target genes of differential miRNA were predicted . Gene Ontology (GO) and KEGG Pathway enrichment analysis were used to understand the function of differential miRNA , and the differential miRNA⁃mRNA⁃Pathway regulatory network was constructed using Cytoscape to further screen the regulatory key miRNA and key pathways . qRT⁃PCR was used to verify the expression of selected miRNA . Results : Compared with the model group , the glycyrrhizin group could significantly improve the liver tissue lesions , and reduce the liver serum AST and ALT levels (P < 0. 05) . Compared the microarray data of glycyrrhizin group and model group , a total of 13 differentially expressed miRNA were screened ( P < 0. 05 , fold change ≥ 1 . 5) , of which 10 were up⁃regulated and 3 were down⁃regulated . The GO classification annotation of differential miRNA target genes showed that differential miRNA were related to cell adhesion , antioxidant activity , metabolic process , biological process regulation , cell killing , immune system and other functions . The KEGG Pathway analyling pathway , Hippo signaling pathway , PI3K⁃Akt signaling pathway , wnt signaling pathway , apoptosis and other signaling pathways might play an important regulatory role in the improvement of alcoholic liver injury by glycyrrhic acid . Conclusion This study established the miRNA expression profile of glycyrrhizin in the treatment of alcoholic liver injury in rats , suggested that miR⁃615 , miR⁃107 ⁃3p and miR⁃292⁃5p might play an important role in the treatment of alcoholic liver injury by glycyrrhizin .