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

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

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.

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

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

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

Objective To investigate the effects of chronic hyperglycemia on the proliferation,secretion function and expression of endoplasmic reticulum stress(ERS) related molecules in pancreatic ? cell line MIN6. Methods MIN6 cells were treated with different concentrations of glucose(5.6,25 and 33.3mmol/L) and were harvested at indicated time(24h and 96h) for examinations.Cell proliferation was tested using CCK-8 solution,insulin and proinsulin secretion function was determined by ELISA,and mRNA expression of ERS related molecules(Total XBP-1,Spliced XBP-1) and protein expression of phosphorylated IRE1? were detected by Real-time PCR and Western blotting,respectively. Results After treatment with hyperglycemia for 96h, cell proliferation was significantly lower than that treated for 24h(P

AIM:To compare the clinical effect of 23G and 25G+ vitrectomy for treatment of proliferative diabetic retinopathy (PDR).METHODS: A total of 128 PDR patients (195 eyes) requiring vitrectomy in our hospital from November 2013 to May 2016 were randomly divided into 25G+ group and 23G group, 64 cases (97 eyes) in 25G+ group and 64 cases (98 eyes) in 23G group.In 25G+ group, patients were treated by 25G+ vitrectomy.In 23G group, patients were treated by 23G vitrectomy.The visual acuity, as well as intraocular pressure (IOP), iatrogenic injury and complications in two groups were recorded before and 1d, 1wk, 1mo after treatment.The operation time was compared between two groups.RESULTS: The operation time in 25G+ group was lower than that in 23G group (P<0.05).The postoperative visual acuity at 1mo of two groups were improved compared with before surgery (P<0.01).However, visual acuity between two groups in the same period had no significant difference (P>0.05).IOP in 25G+ group before surgery had no significant difference compared with those after surgery at 1d,1wk, and 1mo(P>0.05), which it was the same in 23G group.IOP of two groups in the same period had no significant difference (P>0.05).The incidence rate of iatrogenic injury in 25G+ group was 4.1%, which was significant lower than that of 23G group (13.3%) (P<0.05).The incidence rate of complication in 25G+ group was 3.1%, which was significant lower than that of 23G group (11.2%) (P<0.05).CONCLUSION: Both 23G and 25G+ vitrectomy are safe and effective treatment for PDR.However, 25G+ vitrectomy is the better choice for PDR for the shorter operation time, lower incidence rate of iatrogenic injury and fewer surgical complications.