Colorectal cancer is a common malignant tumor in the gastrointestinal tract, with the characteristics of high morbidity and mortality. Studies have shown that the occurrence and development of colorectal cancer is closely related to the abnormal activation of Wnt signaling pathway. Abnormal expression of β-catenin in Wnt pathway is found both in the cytoplasm and nucleus of tumor cells. Different drugs can target the Wnt signaling pathway and its upstream and downstream related factors to inhibit or suppress the development of colorectal cancer. We review the components of Wnt signaling pathway, and the correlation between Wnt signaling pathway and colorectal cancer. Then, we summarize the current status of drug research targeting the Wnt signaling pathway in colorectal cancer. Finally, the challenges and prospects of these methods and drugs were briefly summarized.

AIMTo explore the effects of interleukin-1beta (IL-1beta) on inducible nitric oxide synthase (iNOS)-nitric oxide (NO) system activity in arginine vasopressin (AVP)-induced rat cardiac fibroblasts (CFs).

METHODSCFs were isolated by trypsin digestion method. Nitric acid reductase method, spectrophotometry and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect NO contents, NOS activity and iNOS mRNA expression.

RESULTSAVP significantly increased iNOS mRNA expressions, NOS activity and NO contents (P < 0.05) in CFs. IL-1beta enhanced the effects of AVP on iNOS-NO system activity in a concentration-dependent manner, moreover the iNOS mRNA expressions, NOS activity and NO contents of AVP + 3 ng/ml, AVP + 5 ng/ml IL-1beta group were both significantly higher than those of AVP group (P < 0.05). But when IL-1beta concentration increased to 5 ng/ml, the iNOS mRNA expressions, NOS activity and NO contents did not increase accordingly, slightly decreased instead.

CONCLUSIONWithin certain range of concentrations IL-1beta cooperates with AVP to increase iNOS-NO system activity in CFs.

Animals ; Arginine Vasopressin ; pharmacology ; Fibroblasts ; drug effects ; metabolism ; Interleukin-1beta ; pharmacology ; Male ; Myocytes, Cardiac ; drug effects ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley

Drug transport is an important source of inter-individual variations in drug responses and is also a common site where drug-drug interactions happen. In recent years, more and more novel identified transporters have been added into the transporter super family, and this trend will continue in the future. Among the transporter members of this family, ATP-dependent efflux transporter P-glycoprotein (MDR1) and organic anion transporters (OATP) are the most important proteins involved in drug transport. MDR1 is the most well known transporter. Widely distributed in tissues such as the gastrointestinal tract, liver, kidney and so on, MDR1 plays an important role in drug absorption, distribution and excretion. Its functional genetic polymorphisms have significantly changed the pharmacokinetics of its substrate drugs, which has important clinical implications. OATP expressed in multiple tissues, and it mediated the drug excretion through the bile acid and kidney. Some genetic polymorphism of OATP genes is the cause of some abnormal drug responses.
ATP Binding Cassette Transporter, Subfamily B, Member 1 ; genetics ; Drug Interactions ; genetics ; Humans ; Membrane Transport Proteins ; genetics ; metabolism ; Organic Anion Transporters ; genetics ; Pharmaceutical Preparations ; metabolism ; Polymorphism, Genetic

Aim To determine potential biomarkers contributed to occurrence, development and recovery of ethanol-induced liver injury in rat and elucidate hepatoprotective effect of Yin Chen Hao Tang based on metabonomic investigation. Methods A UPLC-Q-TOF/MS based metabonomic method was developed for investigating trajectory change and inter-relationship of urinary metabolome of rats with different treatments. Results Four potential biomarkers were determined which contributed to occurrence, development and recovery of ethanol-induced liver injury in rat, and Yin Chen Hao Tang could significantly recover trajectory change in disorder. Conclusion The developed method was successfully applied to investigate ethanol-induced liver injury in rat, and also hepatoprotective effect of Yin Chen Hao Tang was elucidated.

Objective To investigate the potential role of angiotensinⅡ(AngⅡ)-angiotensinⅡreceptor 1 (ATRI) pathway on inflammatory activation in the lung of rats. Method Twenty four Sprague-Dawley rats were randomly divided into four groups: control group, Ang II group, AngⅡ+losartan group and losartan group. Lung wet/dry weight (W/D) was recorded to assess lung injury. The total lung homogenates were prepared to detect nuclear factor-kappa B (NF-?B) activation by electrophoretic mobility gel shift assary (EMSA), tumor necrosis factor (TNF)-?mRNA expression by reverse transcription polymerase chain reaction (RT-PCR), myeloperoxidase (MPO) and malondialdehyde (MDA) by colorimetry. Plasma yon Willebrand Factor (vWF) were assessed by enzyme-linked immunosorbent assay (ELISA). Meanwhile, pathological changes were examined under optical microscope. Results Histologically, alveolar edema, hemorrhage, and massive inflammatory cell infiltration were observed in AngⅡgroup, but not in control group and losartan group. Compared with AngⅡgroup, histological injury was lesser in AngⅡ+ losartan group. In AngⅡgroup, lung W/D, NF-?B activation, TNF-?mRNA expression, MPO, MDA and vWF were markedly higher than those in the other three groups. There were not significant differences of lung W/D, NF-?B activation, TNF-?mRNA expression, MPO, MDA and vWF in control group, AngⅡ+ losartan group and losartan group. Conclusions Systemic infusion of AngⅡcould up- regulate inflammatory mediator expression and induce lung injury in rats. AngⅡ, acting mainly through ATRI, induced inflammatory activation in the lung of rats.

0.05).Expressions of IL-2 in tears significantly decreased 1 d,1 week and 1 month after LASIK(P0.05).Compared with the expression of NGF in tears before operation,those of 1 d,1 week,1 month and 3 months after LASIK were significantly increased(P

The methyl group plays an important role in the rational drug design. Introducing methyl into small molecules has become an important strategy of lead compound optimization. The application of methyl in drug design is reviewed in this paper. Methyl can modulate the physicochemical, pharmacodynamic, and pharmacokinetic properties by ortho effect, inductive effect, and conformational effect. It also improves the metabolic stability as a soft metabolic point. In addition, introducing methyl into drug molecules can also be applied as a strategy in new uses of old drugs and generate me-too drugs.
Drug Design ; Hydrophobic and Hydrophilic Interactions ; Lipid Metabolism ; Methylation ; Pharmaceutical Preparations ; chemical synthesis ; chemistry ; metabolism ; Solubility ; Stereoisomerism ; Structure-Activity Relationship

Objective Toinvestigatetheeffectsoflongnon-codingRNAurothelialcarcinoma-associated1(lncRNA UCA1) silencing on cell proliferation and invasion of human hepatic cancer HepG2 cells, and its mechanism thereof. Methods TheexpressionoflncRNAUCA1wasanalyzedbyreal-timePCRin20tumortissueand20adjacentnon-tumor tissuesamplesofhepaticcancer.HepG2cellswasculturedin vitro,andlncRNAUCA1specificshorthairpinRNA(shRNA1 andshRNA2)wastransfected.CCK-8assay,TranswellassayandWound-healingassaywereusedtodetecttheeffectof lncRNAUCA1silencingoncellproliferation,invasionandmigrationofHepG2cells.TheeffectoflncRNAUCA1silencing onproteinandmRNAexpressionofCyclinD1,vascularendothelialgrowthfactor(VEGF),matrixmetalloproteinase(MMP)9,focaladhesionkinase(FAK)andIntegrinβ3onlncRNAUCA1silencingwasmeasuredbyreal-timePCRandWestern blotassay.Results TheexpressionofLncRNAUCA1washigherinhepaticcancertissues.ThesilencingoflncRNAUCA1 significantly inhibited the growth of HepG2 cells, and the abilities of cell invasion and migration were downregulated. Westernblotassayandreal-timePCRshowedthatexpressionsofCyclinD1,VEGF,MMP-9,FAKandIntegrinβ3were significantlyinhibited.Conclusion TheresultssuggestthattheabnormalexpressionoflncRNAUCA1isassociatedwith thedevelopmentofhumanhepaticcancer.ThesilencingoflncRNAUCA1couldsuppressthecellproliferation,invasionand migrationofhepaticcarcinomacells.

OBJECTIVEThe study was aimed to investigate the inhibitory effect and mechanism of astragaloside IV (ASI) on the activation of microglial cells.

METHODAfter pre-incubated with ASI for 2 h, microglial cells BV-2 were stimulated with interferon-γ (IFN-γ) for 1. 5 h and 24 h, respectively. Secretion of nitric oxide (NO) in the medium was measured by Griess method. Production of tumor necrosis factor alpha (TNF-α) was detected by ELISA approach. Cellular gene expressions of CD11b, TNF-α, interleukin 1β (IL-1β) and induced nitric oxide synthase (iNOS) were examined by quantitative-PCR analysis. Total and phosphorylation of STAT1, IκB and NF-κB was analyzed by Western blot method.

RESULTASI could significantly inhibit the increased secretion of TNF-α and NO from BV-2 cells upon IFN-γ stimulation (P < 0.001). Further study showed that ASI significantly down-regulated gene expression of IL-1β and TNF-α (P < 0.01, P < 0.05) and exhibited a trend to reduce that of iNOS. IFN-γ and ASI have no obvious effect on gene expression of CD11b. Moreover, ASI inhibited the phosphorylation of STAT1, IκB and NF-κB elicited by IFN-γ stimulation.

CONCLUSIONASI could restrain microglial activation through interfering STAT1/IκB/NF-κB signaling pathway, reducing gene expres- sion of IL-1β and TNF-α, and thus inhibiting the production of proinflammatory mediators such as NO and TNF-α.

Animals ; Astragalus Plant ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; I-kappa B Proteins ; genetics ; metabolism ; Interferon-gamma ; genetics ; metabolism ; Mice ; NF-kappa B ; genetics ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; STAT1 Transcription Factor ; genetics ; metabolism ; Saponins ; pharmacology ; Signal Transduction ; drug effects ; Triterpenes ; pharmacology

BackgroundIt is important to measure the corneal curvature, anterior chamber depth (ACD) and axial length accurately for calculating IOL power. The interchange outcomes from different measuring methods and apparatus will cause unreliable IOL power. ObjectiveThe present study was to compare the differences of corneal curvature, anterior chamber depth (ACD) measured by IOLMaster and Orbscan Ⅱbefore and after laser in situ keratomileusis(LASIK) and further compare the axial length measured by IOLMaster and A-ultrasound. Methods One hundred and thirty eyes from 65 consecutive myopic patients before LASIK and 56 eyes of 28 cases with 1-month follow-up duration after LASIK in Henan Eye Institute were enrolled in this study. The K value, ACD between IOLMaster and Orbscan Ⅱ as well as results of axial length between IOLMaster and A-ultrasound were compared by using paired t test. The agreements of the measured values among IOLMaster, Orbscan Ⅱ and A-ultrasound were evaluated using Bland-Altman plot. ResultsBefore LASIK,the K value measured by IOLMaster,Orbscan Ⅱ were ( 43.32 ± 1.52 ) D and ( 42.99 ± 1.45 ) D respectively with the difference value of( 0. 33 ±0. 03 ) D, showing a significant difference(t=10. 380,P=0.000) and a positive relation between them(r=0.971,P=0.000). After LASIK,the K value measured by IOLMaster, Orbscan Ⅱwere(39. 02±2. 14) D and ( 38.91 ±2. 04) D with the difference value (0. 12±0. 33 ) D, presenting a significant differences between them (t =2.715, P =0.009). Bland-Altman plots indicated the disagreement in K value and uninterchangeable. Before LASIK, the ACD measured by IOLMaster,Orbscan Ⅱ and A-ultrasound were ( 3.72 ± 0. 22 ) mm, ( 3.69 ±0. 22 ) mm and ( 3.75± 0.27 )mm respectively and no significant differences were found between them (P ＞ 0. 05 ). Axial length measured by IOLMaster significantly prolonged in comparison with A-ultrasound(25.59± 1. 01 mm vs 25.22±0.99 mm ) , and the difference was( -0. 37 ±0. 30 ) mm, showing significant difference ( t =- 14. 098, P =0. 000 ) and positive correlation ( r =0. 954, P =0. 000 ). Axial length values measured by IOLMaster were ( 25.54 ± 1.05 ) mm in preoperation and ( 25.48 ± 1.01 ) mm in postoperation with the difference (0.052±0. 412)mm, showing statistically insignificant difference between them (t=0. 946,P=0. 348). ConclusionsKeratometries measured by IOLMaster,Orbscan Ⅱ are much more different. Therefore,these two methods are not recommended to use interchangely. ACD measured by IOLMaster,Orbscan Ⅱ and A ultrasound are proved to obtain the similar results and is clinically interchange. Axial length measured by IOLMaster is longer than that measured by A-ultrasound.