As an important member of the adisintegrin and metalloproteinase (ADAM) superfamily,ADAM17 can mediate a variety of membrane molecular hydrolysis off,such as adhesion molecules,cytokines,growth factors,etc,and play an important role in regulating tumor cell adhesion,apoptosis,metastasis and proliferation through the EGFR-PI3K-Akt pathway,Notch signaling pathway and other signaling pathways.The research of ADAM17 targeted drugs provides a new direction for cancer therapy.

AIM:To analyze the expression profile of long non-coding RNA (lncRNA) in the liver tissues of drug-induced liver injury ( DILI) and immune liver injury ( ILI) .METHODS:The technique of lncRNA microarray was used to inspect the lncRNA expression profile in the mouse liver tissues that the liver injury was induced by acetaminophen or concanavalin A .The raw data of lncRNA were pretreated for normalization .RESULTS:Compared with normal hepatic tissue, the lncRNA which had more than 1.5-fold variation and significant difference (P<0.05) by statistical analysis were regarded as lncRNA with differential expression .A total of 68 lncRNA with differential expression were found in the hepatic tissues of DILI, with 21 increased more than 1.5 folds and 47 reduced more than 1.5 folds.A total of 60 lncRNA with differential expression in the liver tissues of ILI were observed , with 17 increased more than 1.5 folds and 43 reduced more than 1.5 folds.In all lncRNA, 8 was simultaneously up-regulated in 2 liver injury models , accounting for 38%and 47%respectively, while 28 was simultaneously down-regulated in 2 liver injury models, accounting for 59%and 65%re-spectively .CONCLUSION:lncRNA expression profiles of DILI and ILI change significantly in comparison with normal hepatic tissue , and there are also differences between 2 hepatic damage models .The simultaneous changes of lncRNA may participate in the same or similar pathophysiological process , while the differences may be involved in relatively particular mechanisms .

OBJECTIVE: To compare the differences of macrophages phagocytic activities between Dioscorea opposita Thunb. cv. Tiegun(abbreviated as TG) and Dioscorea opposita Thunb. but not Tiegun(abbreviated as NTG). METHODS: CCK-8 assay was used to test the cytotoxicity. On the basis of non-toxic dose, the high content screening(HCS) cell imaging analysis was applied to test the phagocytic ability of RAW264.7 cells engulfing GFP-E. coli in vitro, and the phagocytic rates between different kinds of samples at various concentrations were calculated. Furthermore, the biological potency was measured according to the qualitative response parallel method to better evaluate the difference of TG and NTG, by translating phagocytic rates into biological potency. RESULTS: At the range of 0.695 - 5.56 mg(crude drug) •mL-1, all 11 batches samples have no toxicity. The results of HCS displayed that every sample could promote cell phagocytic activity in varying degrees at a certain concentration. RAW264.7 cells could engulf the GFP-E. coli, and the images of HCS reflected the situation of phagocytosis clearly. In addition, the results of biopotency showed that the biopotency value of different samples was between 39.56 to 100, and the average biopotency value of TG was significantly higher than NTG (P < 0.05). CONCLUSION: In vitro experiments showed that all the samples could promote the phagocytic activity of RAW264.7 cells at different degrees. And the average biopotency value of TG was significantly higher than NTG, which is consistent with the saying that "TG has a better quality".

METHODS: Female Kunming mice were randomly divided into five groups, ie, blank control group, low-dose group, middle-dose group, high-dose group, and the positive control group. The three treatment groups were given various doses of Rhodiola granules, ie, 0. 1, 1, 3 g��kg-1 respectively, the positive control group were given Nuodikang capsules at 280 mg��kg-1, and the blank control group was given deionized water for 35 d. The levels of SOD, MDA, GSH-PX in serum, liver, and brain were determined. For the experiment in vitro, with vitamin C as the control drug, the absorbance of Rhodiola granule solution at concentrations of 0.01, 0.1, 1, 10 mg��mL-1 was measured, and the activity of scavenging superoxide anion free radicals and hydroxyl free radicals was calculated.

Background:Tripterygium glycosides(TG)is effective for treatment of ulcerative colitis(UC)in clinical practice, however,the underlying mechanism has not been clarified yet. Aims:To investigate the therapeutic effect of TG on dextran sulfate sodium(DSS)-induced experimental colitis in mice and its possible mechanisms. Methods:Sixty healthy male BALB/ c mice were randomly divided into six groups:model control group,low,medium and high-dose TG group,blank control group and normal control group. Mice in the first four groups drank 5% DSS freely for 7 days to induce experimental colitis;simultaneously,distilled water,9. 01,27. 03 or 81. 09 mg/(kg·d)TG were given intragastrically for 21 days in these four groups,respectively. Histopathological changes of colonic mucosal tissues were observed;expressions of TLR4 mRNA and protein were determined by RT-PCR and Western blotting;expression of NF-κB p65 was detected by immunohistochemistry;concentrations of IL-1α,TNF-α and IL-13 were measured by ELISA. Results:Tissue damage and inflammation in varying degrees were observed in colonic mucosal tissues in TG groups with different dosage,but all were less severe than those in model control group. Expressions of TLR4 mRNA,TLR4 protein,and NF-κB p65 in colonic mucosal tissues,as well as concentrations of IL-1α and TNF-α in supernatant of colonic homogenate were significantly lower in TG groups than those in model control group(P < 0. 01). These parameters in medium and high-dose TG groups were significantly lower than those in low-dose TG group(P < 0. 05),but higher than those in blank control group and normal control group(P < 0. 05). Except for TNF-α,no significant differences were seen between medium and high-dose TG groups(P > 0. 05). Conclusions:TG exerts a protective effect on DSS-induced experimental colitis in mice. The underlying mechanism of its anti-inflammatory effect might be related with the inhibition of TLR4 / NF-κB signaling pathway activation and subsequently suppressing downstream proinflammatory cytokines expression and secretion.

Aim To detect the expression of hippocam-pus NGF gene in the mouse model of Parkinson 's dis-ease. Methods By intraperitoneal injection of 1-meth-yl-4-phenyl-1,2, 3, 6-tetrahydropyridine ( MPTP), a mice model of Parkinson ’ s disease was established. The success of PD model was identified by detecting the expression of mesencephalic tyrosine hydroxylase ( TH) with Western blot and immunofluorescence. The movement and cognitive ability of mice were evaluated by foot print analysis and step-through passive avoid-ance test. The expression of NGF gene in hippocampus of mice was detected with RT-PCR and in situ hybrid-ization. Results Compared with the control group, the levels of TH and NGF were reduced in the experi-mental group and the behavioral indexes were deflected significantly. Conclusion NGF may play an impor-tant role in the occurrence and development of the PD cognitive disorder.

AIM: To observe the effect of Tripterygium glycosides on NOXs-ROS-NLRP3 inflammatory signa-ling pathways in the colon tissue in dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) mice, and to investi-gate the underlying mechanisms.METHODS: BALB/c mice were used and the mouse model of UC was established by DSS induction.The mice were randomly divided into 5 groups (model group, low-, medium-and high-dose Tripterygium glycosides groups, and normal group).The colon tissues were collected 21 d after Tripterygium glycosides gavage.The mRNA expression of NLRP3, ASC and caspase-1 in the colon tissues was detected by real-time PCR.The caspase-1 ex-pression in the colorectal mucosa was observed by immunohistochemical method.ELISA was used to detect the protein le-
vels of IL-1α, TNF-αand IL-13.The production of reactive oxygen species (ROS) was measured by chemiluminescence technique, and the consumption rate of NADPH, which was inhibited by DPI, was analyzed to determine the activity of NADPH oxidases (NOXs).The neutrophils were isolated, and the ROS production, NOXs activity, and the mRNA ex-pression of NLRP3, ASC and caspase-1 were also detected.RESULTS: The colon tissues were abnormal with different de-grees in Tripterygium glycosides groups, and histopathological scores were lower than that in model group.In Tripterygium glycosides groups, in addition to the mRNA expression levels of caspase-1 in the colon tissues between normal group and high-dose group, ROS production, NOXs activity and the mRNA expression levels of NLRP3, ASC and caspase-1 in the colon tissues and colon-isolated neutrophils were lower than those in model group (P <0.05), and higher than those in normal group (P <0.05).The results of pairwise comparison for the efficacy of Tripterygium glycosides administration showed that the above indexes were statistically significant except the mRNA expression levels of caspase-1 between middle-dose group and high-dose group.Tripterygium glycosides administration significantly decreased the expression levels of proinflammatory cytokines IL-1αand TNF-αin the homogenates of colon tissues in the model mice (P <0.05).No differ-ence of IL-13 expression among the groups was observed.CONCLUSION: Tripterygium glycosides inhibits NOXs-ROS-NLRP3 inflammatory signaling pathways to reduce the expression of IL-1α, TNF-αand other proinflammatory cytokines, and attenuates DSS-induced ulcerative colitis in mice, by which the neutrophils might be involved in the process.

Objective To investigate the expression of IL-8 and CXCR2 on keratinocytes from psoriatic lesions and their roles on clinical and pathologic manifestations. Methods The chemotaxis of psoriatic lesional keratinocytes was detected by micropore loculus test. The concentration of IL-8 was determined in the cultured supernatants of psoriatic keratinocytes by ELISA. The expression of CXCR2 on keratinocytes from affected skin was tested by flow cytometry. Results The chemotaxis for neutrophils by the cultured supernatants of psoriatic lesional keratinocytes was significantly stronger than that by controls. The concentration of IL-8 in the cultured supernatants of psoriatic lesional keratinocytes was also increased. The expression of CXCR2 on psoriatic keratinocytes was significantly increased. Conclusions The psoriatic epidermal hyperproliferation may be correlated with up regulation of IL-8 production and CXCR2 expression on psoriatic keratinocytes. At the same time, the psoriatic inflammation may be partly related to the increase of secretion of IL-8, which has chemotactic capacity, by keratinocytes. IL-8 and CXCR2 may be involved in the pathogenesis of psoriasis.

Objective To construct eukaryotie vector of human neronal pentraxin 2 (NPTX2),and obtain the sstable transfected PANC1 cell lines.Metods The full-length cDNA of NPTX2 was diget EcoRl and Notl,and was cloned into plasmid pcDNA3,1,which were confirmed by sequencing,then the PcDNA3,1(+)and pcDNA3,1(+)-NPTX2 vectors were transfected into PANC1 cells by LipofectamineTM 2000,The stable transfected PANC1 cell lines were selected by the abiliy of resistanc to G418.The NPTX2 mRNA expression of PANC1 in the selected clones was detected by real-time quantitative PCR.Results The eukaryotic vector pcDAN3,1(+)-NPTX2 was constructed successfully,stable transfected PANC1 cell line was established and confirmed by real-time quantitative PCR.Conclusions The construction of eukaryotic vector targeting NPTX2 and the established sstable transfected PANC1 cell line provided a solid experimental foundation for further studies on the function of NPTX2 in pancreatic cancer cells.

Child ; Female ; Gastric Mucosa ; pathology ; Gastritis, Hypertrophic ; diagnosis ; Humans ; Hypertrophy ; diagnosis