【Abstract】ObjectiveTo investigate the role of PPARδ in the pathogenesis of colorectal cancer. MethodsLiteratures about PPARδ and the pathogenesis of colorectal cancer were reviewed and analyzed.ResultsPPARδ is expressed in the nucleuses of glandular epithelia lining colon and rectum. It is normally suppressed by wild-type adenomatous polyposis coli (APC) but is up-regulated by enhanced β-catenin/T cell factor-4 (TCF-4) binding to TCF-4-responsive elements in the PPAR promoter when an inactivating APC mutation occurs, which indicates PPAR is a potential downstream target of the APC/β-catenin/TCF-4 signaling pathway in colorectal cancer. Consistent with PPAR’s role as an APC/β-catenin/TCF-4 target, some studies reported that PPAR mRNA is frequently overexpressed in colorectal cancers of both humans and rodent animals, which indicates that PPAR is relevant to the tumorigenesis of colorectal cancer. ConclusionPPARδ is closely related with the pathogenesis of colorectal cancer.
【 Abstract 】 Objective To investigate the effects of 250 ml/m3 carbon monoxide (CO) inhalation or intraperitoneal infusion on lipopolysaccharide (LPS) induced rat intestinal tract injury, and to detect the roles of p38 mitogen-activated protein kinase (MAPK) pathway during CO administration. Methods After received 5 mg/kg LPS or an equal volume of normal saline by intravenous injection, 108 male SD rats were randomly divided into 6 groups: control group, CO inhalation (250 ml/m3) group, CO intraperitoneal infusion (250 ml/m3 at a rate of 2 L/min) group, LPS (5 mg/kg) group, LPS (5 mg/kg)+CO inhalation (250 ml/m3) group and LPS (5 mg/kg)+CO intraperitoneal infusion (250 ml/m3 at a rate of 2 L/min) group. The animals were differently sacrificed at 1, 3 and 6 h for the observation, and the ileum tissues were homogenized for determination the levels of platelet activator factor (PAF), intercellular adhesion molecule-1 (ICAM-1) and interlukin-10 (IL-10) with enzyme-lined immunosorbent assay, the content of maleic dialdehyde (MDA) with thiobarbitric acid, the activity of myeloperoxidase (MPO) with chemical method, the activity of superoxide dismutase (SOD) with hydroxylamine, the activity of phosphorylated p38 MAPK with Western blot, the pathology with light microscope, and the extents of cell apoptosis were showed by the ratio of the apoptotic cells which had less DNA to the total cells of a cell-suspension sample by using the flow cytometry after being stained with propidium iodide. Results Compared with both control, CO inhalation and intraperitoneal infusion group at the same time point, the levels of PAF, ICAM-1, MDA, MPO, cell apoptosis rate and the phosphorylated p38 MAPK protein in LPS group were increased, while IL-10 and SOD were decreased (P ＜ 0.05 or 0.01), and accompanied by severe intestinal tract injury. There were no statistics differences at the different time point in the same group. PAF, ICAM-1, MDA, MPO and cell apoptosis rate in both LPS+CO inhalation group and LPS+CO intraperitoneal infusion group were lower, while IL-10 and SOD were higher than the corresponding value in LPS group at the same time point (all P ＜ 0.05), with ameliorate injury too, but the expression of phosphorylated p38 MAPK was further up-regulated than that of LPS group (all P ＜ 0.05). However, there were no significant differences in these parameters between LPS+CO inhalation group and LPS+CO intraperitoneal infusion group. Conclusion 250 ml/m3 CO inhalation and intraperitoneal infusion exerts the similar protection against LPS induced rat intestinal tract injury via anti-oxidant, anti-inflammation, and anti-apoptosis. This may involve the p38 MAPK pathway.
Objective To systemically review the effectiveness and safety of human recombinant activated protein C (rhAPC) for severe sepsis. Methods Such databases as MEDLINE, EMbase, The Cochrane Library, VIP, CNKI and CBM were electronically searched for comprehensively collecting randomized controlled trials (RCTs) on the effectiveness and safety of human recombinant activated protein C (rhAPC) for severe sepsis from inception to July 2012. References of included studies were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.0 software. Results Totally, five RCTs involving 6 307 patients were included. The results of meta-analysis showed that, no significant difference was found in 28-day mortality (RR=1.00, 95%CI 0.84 to 1.19, P=1.00) and 90-day mortality (RR=1.00, 95%CI 0.87 to 1.14, P=0.96) between the rhAPC group and the placebo group. The results of subgroup analysis showed that, the two groups were similar in the 28-day mortality of patients with different Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (APACHE II scorelt;25: RR=1.06, 95%CI 0.93 to 1.21, P=0.37; APACHE II score≥25: RR=0.93, 95%CI 0.69 to 1.24, P=0.60), and in the 28-day mortality by protein C deficiency class (APC deficiencylt;80%: RR=0.96, 95%CI 0.56 to 1.65, P=0.89; APC deficiencygt;80%: RR=0.61, 95%CI 0.34 to 1.08, P=0.09). Besides, bleeding risk in the rhAPC group was 1.62 fold more than that in the placebo group (RR=1.62, 95%CI 1.17 to 2.23, P=0.004). No significant difference was found in the incidence of adverse reaction (RR=1.04, 95%CI 0.92 to 1.18, P=0.53). Conclusion Current evidence suggests that, rhAPC could not improve the prognosis of patients with severe sepsis, but it significantly increases bleeding risk.
Objective To explore the possible anti-inflammatory mechanism of peroxisome proliferators-activated receptor（PPAR） gamma-agonists by investigating the effects of Rosiglitazone on the expression of phosphorylation of signal transducer and activator of transcription 6（p-STAT6） and the secretion of interleukin（IL）-4 in T-lymphocytes from patients with acute asthma.Methods Peripheral blood T-lymphocytes from 10 healthy volunteers（group A） and 10 patients with acute asthma were isolated，purificated and cultured.T-lymphocytes from the asthma patients were divided into a control group（group B） and a Rosiglitazone treated group（group C）.Rosiglitazone was added with a single dose of 10-4 mol/L at 0 hour of cultrue.After cultured for 48 hours，the concentration of IL-4 in supernatant of each groups were detected by ELISA.The express of p-STAT6 in the T-lymphocytes were determined by Western blot and immunohistochemical techniques.Results The levels of IL-4 were increased markedly in group B than those in group A and group C[（170.34±9.05）pg/mL vs（76.82±7.06）pg/mL and（123.59±8.70）pg/mL，both Plt;0.01]，and which in group C was significantly lower than group A（Plt;0.01）.The levels of p-STAT6 in T lymphocytes were increased markedly in group B than in group A and C[Western blot：（6.28±0.19 vs 3.07±0.18 and 4.12±0.16；immunohistochemistry：（36.58%±7.41）% vs（11.39±4.02）% and（23.92±5.8）%，all Plt;0.01），and which in group C were significantly higher than that in group B（both Plt;0.01）.There was a positive correlation between the level of p-STAT6 and IL-4（Plt;0.01）.Conclusion The levels of p-STAT6 and IL-4 in T-lymphocytes of patients with acute asthma were suppressed by Rosiglitazone in vitro.
Adenosine activated protein kinase (AMPK) is a serine/threonine protein kinase that can sense the change of intracellular energy. AMPK plays a critical part in the occurrence and development of tumors. According to the difference of AMPK catalytic subunits, it is divided into AMPKα1 and AMPKα2. The AMPKα1 subunit is the catalytic subunit of AMPK and is extensively distributed in the various tissues and organs. This review focuses on the structural, activated and functional aspects of AMPKα1 and the involvement of AMPKα1 in the regulation of intracellular substance metabolism, and summarizes the respective performances of AMPKα1 in different cancers and the corresponding potential applications of AMPKα1 as a drug target in the relevant cancers. AMPKα1 can be used as a diagnostic marker or drug target for cancer diagnosis and therapy, providing an idea for cancer treatment, which has importance clinical significance.
Objective To explore the activity of Ca2 + -activated K+ ( KCa) inairwaysmoothmuscle cells( ASMCs) in a rat model of chronic obstructive pulmonary disease( COPD) , and to observe the effect of 11, 12-Epoxyeicosatrienoic acid( 11, 12-EETs) on the KCa channel of ASMCs. Methods Forty male Sprague-Dawley rats were randomly assigned to a COPD group and a normal control group. The rats in the COPD group were exposed to cigarette smoking in a relatively closed chamber to induce COPD. The ASMCs were isolated from small bronchi using an acute enzymatic digestion method. In the symmetrical high K+ solution,the KCa currents were separated with inside-out configuration using the patch clamp technique. The activity of KCa currents in ASMCs between the COPD group and the normal group were compared and the effect of 11, 12-EETs on KCa channel was recorded. The opening probability( Po) , opening time( To) and closing time ( Tc) of the KCa were measured. Results Compared with the normal group, Po of KCa in the COPD rats was much shorter ( 0. 084 ±0. 028 vs 0. 198 ±0. 029, P lt; 0. 01) , To was shorter [ ( 0. 732 ±0. 058) ms vs ( 1. 648 ±0. 152) ms, P lt; 0. 01] and Tc was longer[ ( 12. 259 ±2. 612) ms vs ( 6. 753 ±1. 237) ms, P lt;0. 01] . 11, 12-EETs can evoke the activity of KCa currents of ASMCs in the COPD rats while Po was increased( 0. 227 ±0. 059 vs 0. 084 ±0. 028, P lt; 0. 01) , To was much longer[ ( 2. 068 ±0. 064) ms vs ( 0. 732 ±0. 058) ms, P lt; 0. 01] , and Tc was shorter [ ( 4. 273 ±0. 978) ms vs ( 12. 259 ±2. 612) ms, P lt;0. 01] .Conclusions The results suggest that the decreasing of KCa activity plays an important role in the development of COPD. 11,12-EETs can directly evoke the activity of KCa channel in COPD rats, thus relax the airway smooth muscles.
ObjectiveTo summarize the research advancement of peroxisome proliferator-activated receptor γ (PPARγ) agonists inhibiting transforming growth factor-β (TGF-β)-induced organ fibrosis. MethodsThe related literatures on PPARγ agonists inhibiting TGF-β-induced organ fibrosis were reviewed. ResultsTGF-β was a major fibrosispromoting cytokine, which could promote a variety of organ fibrosis. PPARγ agonists could effectively block TGFβ signal transduction, and then suppressed organ fibrosis well. ConclusionsThe main antifibrotic mechanism of PPARγ agonists is to inhibit TGF-β signal transduction. The studies on this mechanism will help promoting the clinical application of PPARγ agonists, and provide a new way of the treatment for organ fibrosis.
OBJECUIVE: To observe the therapeutic efficacy of gamma;-knife/lymphokine activated killing cells (LAK)in chorold malignant melanoma (CMM). METHODS:Five cases of CMM had keen treated by retrobulbar injection of LAK cells and gamma;-knife irradiation at multiple sites.Ophthalmologic,imageologic, fundus fluorescein angiographic and T lymphocyte subset examinations were done before and after treatment. Tile follow-up period of this series of cases was 6-24 months. RESUILS:Thc CMM of 4 in 5 treated cases became atrophic and withered up clinically after gamma;-kinfe/LAK therapy. Among the 4 cases,2 of them had been followed up for more than 2 years,and the other 2 for 20 and 14 months respectively. The tumor of the 5th patient wko was followed up for 6 months after treatment,reduced to 3/5 of the original size,and no blood flow was found within thee tumor mass under the clinical examination. CONCLUSION :The gamma;-knife/LAK therapy was effective in treating CMM in saving the affected eye from being enucleated. Chin J Ocul Fundus Dis,1997,13: 96- 98）
【Abstract】Objective To study the regulatory ability of peroxisome proliferatoractivated receptor γ(PPARγ) ligands to the inflammatory response in human gallbladder epithelial cells. Methods Culture human gallbladder epithelial cells and identify them . Cells were treated for 24 hours with 0, 10 μmol/L, 20 μmol/L, 30 μmol/L, 50 μmol/L and 100 μmol/L of Ciglitazone during cellular growth peak(5th day), then stimulated them with hIL-1β 5 ng/ml for 2 hours and measured the concentration of IL-6、IL-8 and TNF-α in cellular supernatants by riadioimmunoassay. Results Contrasted with control group, the expression of IL-6 and IL-8 in each test group were inhibited （P＜0.001）. The IL-6 and IL-8 levels were gradually dropped and corelated with the dosage of Cigtitazone, and manifested dosagedependence (P＜0.001). The concentration of TNF-α could not be measured. Conclusion PPARγ ligands can inhibit the expression of IL-6 and IL-8 in human gallbladder epithelial cells and probably produce effect in the regulation of cholecystic inflammation.
To explore the effects of plasma jet (PJ) and plasma activated water (PAW) on the sterilization of Streptococcus mutans (S. mutans) and compare the advantages and disadvantages of the two methods, so as to provide a basis for plasma treatment of dental caries and to enrich the treatment means of dental caries, an atmospheric pressure plasma excitation system was built, and the effects of PJ and PAW on the sterilization rate of S. mutans and the changes of temperature and pH during treatment were studied under different excitation voltage (Ue) and different excitation time (te). The results showed that in the PJ treatment, the difference in the survival rate of S. mutans between the treatment group and the control group was statistically significant (P = 0.007, d=2.66) when Ue = 7 kV and te = 60 s, and complete sterilization was achieved at Ue = 8 kV and te = 120 s in the PJ treatment. In contrast, in the PAW treatment, the difference in the survival rate of S. mutans between the treatment group and the control group was statistically significant (P = 0.029, d = 1.71) when Ue = 7 kV and te = 30 s, and complete sterilization was achieved with PAW treatment when Ue = 9 kV and te = 60 s. Results of the monitoring of temperature and pH showed that the maximum temperature rise during PJ and PAW treatment did not exceed 4.3 °C, while the pH value after PAW treatment would drop to a minimum of 3.02. In summary, the optimal sterilization parameters for PJ were Ue=8 kV and 90 s < te ≤ 120 s, while the optimal sterilization parameters for PAW were Ue = 9 kV and 30 s<te ≤ 60 s. Both treatment methods achieved non-thermal sterilization of S. mutans, where PJ required only a smaller Ue to achieve complete sterilization, while at pH < 4.7, PAW only required a shorter te to achieve complete sterilization, but its acidic environment could cause some chemical damage to the teeth. This study can provide some reference value for plasma treatment of dental caries.