Objective To investigate the effect of recombinant adenovirus mediatied human endostatin (rAD-GFP-ES)on rats with collagen typeⅡinduced arthritis(CIA),and explore the mechanism of inflamma- tion and cytokines inhibition on rats CIA.Methods The rAD-GFP-ES was amplified and purified.The model of rat CIA was induced by intradermal injection of typeⅡcollagen combined with complete Freund's adjuvant(CFA). On the second day after the injection,the therapeutic administration of rAD-GFP-ES(1?10~(11)pfu?kg~(-1)?week~(-1)?4 weeks)were performed to the rats.The mean arthritis index(AI)was scored every week since then.The relative concentrations of ES,IL-I?,TNF-?in sera collected at the fourth week were evaluated by western blotting. Results①The titer of the purified rAD-GFP-ES and rAD-GFP was 6.6?10~(12)pfu/ml and 4.8?10~(12)pfu/ml,re- spectively(A_(260nm)/A_(280nm)＞1.3).②The concentration of ES in sera of the group treated with rAD-GFP-ES was 2.4-lold higher compared to the normal group.③The mean arthritis index of the group treated with rAD-GFP- ES was much lower than that of the model group.The administration of rAD-GFP-ES could significantly de- creas the production of IL-1?and TNF-?in sera.Conclusions①The rAD-GFP-ES is efficiently expressed in vivo.②The rAD-GFP-ES has an inhibitory effect on the arthritis index of rat CIA.③IL-1?and TNF-?are involved in the pathogenesis of RA.The rAD-GFP-ES has an inhibitory effect on the expression of IL-1?and TNF-?in rat CIA.

OBJECTIVETo detect changes of Foxp3 expression in the decidua in patients with preeclampsia and investigate the correlation of Foxp3-924 (rs2232365) polymorphisms with preeclampsia.

METHODSFrom October 2011 to December 2012, 252 normal pregnant women and 156 preeclampsia patients of Han nationality from the same geographic region were tested for Foxp3-924 genotypes by polymerase chain reaction with sequence-specific primer (PCR-SSP). Sixty-eight of the patients with preeclampsia (33 with mild and 35 with severe preeclampsia) and 30 of the normal pregnant women were also examined for Foxp3 expression in the decidua using immunohistochemical method.

RESULTSFoxp3 positive expression rates in the decidua was 51.52% in mild preeclampsia and 28.57% in severe preeclampsia cases, significantly lower than that in the control group (86.67%, P<0.05). In preeclampsia patients, the frequencies of Foxp3-924G/G, G/A, and A/A genotypes were 0.1346, 0.4615 and 0.4038, respectively, and the frequencies of Foxp3-924A and Foxp3-924 G were 0.6346 and 0.3654, respectively. The genotype frequencies of Foxp3-924G/G, G/A and A/A in the control group were 0.1508, 0.4087 and 0.4405, respectively, and the frequencies of Foxp3-924 A and Foxp3-924 G were 0.6448 and 0.3552, respectively. No significant differences were found in the gene frequencies of Foxp3-924G/A between preeclampsia patients and the control group (P>0.05).

CONCLUSIONThe expression level of Foxp3 in the placental tissue of preeclampsia patients is significantly lower than that in normal pregnant women, suggesting that lowered Foxp3 expression decreases the immunosuppressive function and causes imbalance of immune tolerance between maternal-fetal to induce preeclampsia. Foxp3-924 polymorphisms is not significantly correlated with the occurrence of preeclampsia.

Case-Control Studies ; Female ; Forkhead Transcription Factors ; genetics ; metabolism ; Gene Frequency ; Genotype ; Humans ; Placenta ; metabolism ; Polymorphism, Genetic ; Pre-Eclampsia ; genetics ; Pregnancy

OBJECTIVETo investigate the effect of the exposure to di- (2-ethylhexyl) phthalate (DEHP) during pregnancy on the DNA methylation level of genomes in the testis of the offspring in mice.

METHODSPregnant KM mice were randomly divided into three groups, normal control, corn oil and DEHP-exposed. Corn oil and DEHP (500 mg/[kg x d]) were administrated respectively from gestation day 12.5 (GD 12.5) to postnatal day 3 (PND 3). The testes of the offspring were excised on PND 7, and their genomic DNA was treated with EcoR I /Msp I and EcoR I /Hpa II. The genome-wide DNA methylation patterns of the CCGG sites were detected by methylation-sensitive amplification polymorphism (MSAP). The samples were electrophoresed in the ABI 3730 DNA sequencer and the results analyzed by the Genescan3.1.

RESULTSThe average incidence of DNA methylation was (34.03 +/- 3.05)% in the DEHP-exposed mice, obviously higher than (28.37 +/- 2.37)% in the normal control and (28.58 2.45)% in the corn oil group, with statistically significant differences (P < 0.05).

CONCLUSIONExposure to DEHP during pregnancy increases the DNA methylation level of the genome in the testis of the offspring and affects the apparent genetic modification of the genome, which may be one of the important toxicological causes of the lesion in the reproductive system.

Animals ; DNA Methylation ; drug effects ; Diethylhexyl Phthalate ; pharmacology ; Female ; Genome ; Male ; Mice ; Mice, Inbred Strains ; Pregnancy ; Prenatal Exposure Delayed Effects ; Random Amplified Polymorphic DNA Technique ; Testis ; drug effects

Animals ; Collagen Type I ; metabolism ; Collagen Type II ; metabolism ; Collagen Type III ; metabolism ; Female ; Kinetin ; pharmacology ; Liver ; pathology ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Male ; Rats ; Rats, Wistar ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo observe the chronic combined effects of sodium fluoride and sodium arsenite on the Runx2 and downstream related factors of bone metabolism in SD rats.

METHODSSD rats were divided randomly into nine groups of 6 each by factorial experimental design (half female and half male) , and supplied with the different doses of fluoride, arsenite and fluoride plus arsenite containing in deionized water (untreated control containing 0 mg/kg fluoride and 0 mg/kg arsenite, and low-fluoride and high supplemented with 5 and 20 mg/kg fluoride, and low-arsenite and high supplemented with 2.5 and 10 mg/kg arsenite, and low-fluoride plus low-arsenite, and low-fluoride plus high-arsenite, and high-fluoride plus low-arsenite, and high-fluoride plus high-arsenite, respectively) . After 6 months exposure, the concentration of Runx2, matrix metallopeptidase 9 (MMP-9) ,Osterix, Receptor activator for nuclear factor-κ β ligand (RANKL) were detected by enzyme-linked immunosorbent assay method, respectively.

RESULTSThere were no dental fluorosis found in the control group, low-arsenic group and high-arsenic group. There were significant differences in the constituent ratio of dental fluorosis among the rats from low-fluoride and high-fluoride (that is 5 rats out of 6 and 6 rats out of 6) compared with the control group (0 rat out of 6) (χ(2) = 8.57, 12.00, P < 0.05). The bone fluorine level increased with the increase of fluoride dose, the groups without fluoride supply (control group, low-arsenite and high-arsenite group's geometric mean (minimum-maximum) were 0.005 (0.003-0.009), 0.006 (0.003-0.021), 0.003 (0.002-0.100) mg/g, respectively), low-fluorine groups (low-fluoride group, low-fluoride plus low-arsenite, and low-fluoride plus high-arsenite group were 3.395 (2.416-5.871), 3.809 (1.471-7.799), 1.471 (1.473-6.732)mg/g, respectively) , the high-fluorine groups (high-fluoride, high-fluoride plus low-arsenite, and high-fluoride plus high-arsenite group were 70.086 (46.183-131.927), 69.925 (40.503-96.183), 40.503 (52.622-89.487) mg/g, respectively) and the differences between groups was significant (P < 0.05). The bone arsenic level increased with the increase of arsenite dose. The low-arsenic groups (low-arsenite group, low-arsenite plus low-fluoride, and low-arsenite plus high-fluoride group were 7.195 (5.060-9.860), 6.518 (2.960-12.130), 6.970 (3.400-9.730) µg/g, respectively), the high-arsenic groups (high-arsenite, high-arsenite plus low-fluoride, and high-fluoride plus high-arsenite group's geometric mean(minimum-maximum) were 8.823 (5.760-10.840), 9.470 (7.230-12.860), 8.321 (2.420-17.540) µg/g, respectively) were significantly higher than that in the groups without arsenic supply (control group, low-fluoride and high-fluoride group were 1.785 (0.300-3.750), 2.226 (1.410-3.980), 2.030 (1.040-3.850)µg/g, respectively) (P < 0.05). There was no significant difference of the bone arsenic concentration between low-arsenic and high arsenic group. There was significant positive correlation between fluoride concentration and Runx2, MMP-9, Osterix, RANKL level (the correlation coefficient was 0.647, 0.354, 0.582, 0.613 between fluorine gavage concentration and protein level, the correlation coefficient was 0.559,0.387, 0.487, 0.525 between bone fluorine concentration and protein level, respectively, P < 0.01). There was negative correlation between arsenite gavage concentration with Runx2 level (r = -0.527, P < 0.05) and was no correlation between arsenite gavage concentration with MMP-9, RANKL,Osterix level (P > 0.05). There was interaction between fluoride and arsenite to Runx2, MMP-9, RANKL,Osterix (F = 3.88, 15.66, 2.92, 6.42, respectively, P = 0.01, <0.01, 0.031, <0.01, respectively).

CONCLUSIONThe combined effects of fluoride and arsenic on the Runx2, MMP-9, RANKL, Osterix of bone metabolism showed antagonistic effects.

Animals ; Arsenites ; toxicity ; Bone and Bones ; metabolism ; Core Binding Factor Alpha 1 Subunit ; metabolism ; Environmental Exposure ; Female ; Fluorides ; toxicity ; Fluorosis, Dental ; pathology ; Male ; Matrix Metalloproteinase 9 ; metabolism ; RANK Ligand ; metabolism ; Rats ; Rats, Sprague-Dawley ; Transcription Factors ; metabolism

Objective:To predict the target of active components of Drynariae Rhizoma by the network pharmacology, map related targets of osteoporosis (OP), and analyze key nodes of interaction topologically, so as to comprehensively explore the pharmacological mechanism of anti-op of osteoclasts. Method:Firstly, the main active components of Drynariae Rhizoma were screened out from TCMSP based on the pharmacokinetic characteristics, and the related targets were predicted by Pubchem and Swiss Target Prediction database according to the Two-dimensional/Three-dimensional(2D/3D)structural similarity. Then, through Online Mendelian Inheritance in Man (OMIM) and Pubmed text, known OP therapeutic targets were mined, based on putative targets, String database was imported to build Drynariae Rhizoma treatment target OP interaction network diagram. With the help of CytoNCA software, the interaction key nodes were topologically identified according to relevant node parameters, and then imported into String database to build the protein interaction network graph. Finally, biological functions and metabolic pathways of key nodes were analyzed through DAVID database. Result:Sixteen active components of Drynariae Rhizoma were screened out, and 118 related targets were predicted according to the target prediction technique. Totally 316 known therapeutic targets for OP were retrieved. The protein interaction network was constructed according to the String network database. A total of 97 key nodes were screened via CytoNCA topology. The enrichment analysis showed that Drynariae Rhizoma may play an anti-osteoporosis role by regulating stem cells, osteoblasts, osteoclasts and immune cells through multiple signaling pathways in aspects of proliferation, differentiation, immunity and oxidative stress. Conclusion:Studies based on network pharmacology have shown that Drynariae Rhizoma may play an anti-op role through direct or indirect targets and multiple major signaling pathways and affect the proliferation and differentiation of multiple types of cells, in order to provid a scientific basis for explaining the material basis and mechanism of Drynariae Rhizoma's anti-osteoporosis effect.

The aim of the present study was to investigate the protective effects and underlying mechanisms of Garcinia xanthochymus, a perennial medicinal plant native to Yunnan, China, against HO-induced oxidative damage in rat pheochromacytoma PC12 cells. Preincubation of PC12 cells with fruit EtOAc fraction (fruit-EFr., 12.5-50 µmol·L) of G. xanthochymus for 24 h prior to HO exposure markedly improved cell viability and increased the activities of antioxidant enzymes (superoxide dismutase, catalase, and heme oxygenase-1 [HO-1]), prevented lactate dehydrogenase release and lipid peroxidation malondialdehyde production, attenuated the decrease of matrix metalloproteinases (MMP), and scavenged reactive oxygen species (ROS). Fruit-EFr. also reduced BAX and cytochrome C expression and improved BCL-2 expression, thereby decreasing the ratio of BAX to BCL-2. Fruit-EFr. activated the nuclear translocation of NRF2 to increase HO-1 and induced the phosphorylation of AKT. Its cytoprotective effect was abolished by LY294002, a specific inhibitor of PI3K. Taken together, the above findings suggested that fruit-EFr.of G. xanthochymus could enhance cellular antioxidant defense capacity, at least in part, through upregulating HO-1 expression and activating the PI3K/AKT pathway and that it could suppress HO-induced oxidative damage via PI3K/AKT and NRF2/HO-1 signaling pathways.
Animals ; Antioxidants ; metabolism ; pharmacology ; Apoptosis ; drug effects ; Biological Transport ; Cell Survival ; Cytochromes c ; metabolism ; Fruit ; Garcinia ; Heme Oxygenase-1 ; metabolism ; Hydrogen Peroxide ; NF-E2-Related Factor 2 ; metabolism ; Oxidative Stress ; drug effects ; PC12 Cells ; Phosphatidylinositol 3-Kinase ; metabolism ; Phosphatidylinositol 3-Kinases ; Phosphorylation ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology ; Proto-Oncogene Proteins c-akt ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Signal Transduction ; bcl-2-Associated X Protein ; metabolism

This study was aimed to evaluate the prognostic value of serum IL-6 (sIL-6) in patients with multiple myeloma (MM). The sIL-6 level in 288 patients with MM was retrospectively analyzed, and the clinical characteristics and prognosis in patients with different IL-6 level were compared. The newly diagnosed patients with MM were divided into two groups: the low sIL-6 group (sIL-6 < 100 pg/ml) and the high sIL-6 group (sIL-6 ≥ 100 pg/ml). The results showed that high sIL-6 level was more common in patients with ECOG score>3, myeloma bone disease (MBD) between grade 2 to 4, and high creatinine level. There was no significant differences in age, abnormal karyotype percentage, chromosome 13q14 abnormality percentage, CD138(+)/CD38(+) cells percentage and the level of calcium, phosphorus, albumin, C-reactive protein, β2-MG, lactate dehydrogenase, hemoglobin, platelet between the two groups at diagnosis, and also no significant difference in response to initial induction chemotherapy among the two groups. The overall survival was significantly different between the low and high IL-6 groups (P = 0.04, 35 m vs 29 m), but no difference in time to progress between the two groups (P = 1.93, 23 m vs 14 m). It is concluded that the sIL-6 level correlates with the clinical characteristics and prognosis. Radioimmunoassay is an appropriate measurement for human IL-6 in serum, and suitable for clinical application.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Interleukin-6 ; blood ; Male ; Middle Aged ; Multiple Myeloma ; blood ; diagnosis ; Prognosis ; Retrospective Studies