Administration, Oral ; Animals ; Mice ; Nanoparticles ; toxicity ; Particle Size ; Titanium ; toxicity ; Toxicity Tests, Acute

Objective To explore the effect of fluoride and arsenic pollution on bone metabolism in exposed population. Methods One hundred and fifty-two fluoride and arsenic exposed people were selected from Jiaole village, Yuzhang town, Xingron county, Guizhou province in 2006, and 59 not exposed people from Daguoduo village 13 km away from Jiaole village were selected as control. Urinary fluorine(UF), urinary arsenic (UAs), urinary hydroxyproline (UHYP), cross-linked N-telopeptides of type I collagen (UNTX) and bone strength index(STI) were detected. Results The main effect of fluoride on UHYP and UNTX were statistically significant (F = 9.785, 4.225, P < 0.01 ), but was not significant on STI(F = 0.183, P > 0.05). The main effect of arsenic on UNTX was statistically significant (F = 2.660, P < 0.05 ), but was not significant on UHYP and STI(F = 2.012, 0.183,all P > 0.05). The interaction between fluoride and arsenic on UNTX was statistically significant (F= 2.429, P <0.01), but was not significant on UHYP and STI(F= 1.218, 1.001, all P> 0.05). Conclusions Fluoride exposure can affect the metabolism of collagen and bone resorption, and Arsenic exposure main affect bone resorption, fluoride and arsenic co-exposure have more significant effect on bone resorption. UNTX may be used as biological biomarker of bone metabolism for population co-exposed to fluoride and arsenic in health monitoring.

Objective To investigate the effect of propofol on nNOS expression after focal cerebral ischemia-reperfusion in rats and the possible mechanism of protective effect of propofol on brain. Method Seventy-eight male Wistar rats, weighting 250 ~ 300 g, were randomly divided into 3 groups:(1)Sham operation group (S group, n=6) was performed with scham operation; (2) Ischemia-reperfusion group (group I-R, n=36) was subjected to 2-hour right middle cerebral artery occlusion and then reperfusion was followed, saline (1 mg/kg) was injected into the right lateral cerebral ventricle using microsyringe before reperfusion;(3) Propefol group (group P, n=36) was injected with propofol (1mg/kg) into the right lateral cerebral ventricle using microsyringe right after ischemia. Group I-R and group P were divided into 3 subgroups according to the reperfusion time: 1 h, 3 h and 6 h. The neurological function of all rats were tested before reperfusion. The cerebral infarction area of the whole brain was calculated with TIC staining (n=6). The pathological change of brain was observed from HE staining (n=6) and the nNOS protein expression was obtained by immuno- histochemical method (n=6). Results Compared with I-R group, the neurological function was better in group P(P

Objective To study the value of DSA for hepatic vascular anatomy,and to evaluate the efficacy of portal vein occlusion in rabbits with hepatic VX2 tumor.Methods Twenty New Zealand white rabbits were randomly divided into two groups with 10 in each group,including test group A and positive control group B of ham operation.For the test group A,portal branch ligation(PBL)was performed for the left external branch after 3 weeks of the tumor implantation to the left external lobe.Two weeks later,the DSA of hepatic artery and portal vein were performed in all of the rabbits.Results The total displaying effectiveness of the branches of hepatic artery by DSA was better than that by vascular perfusion.There was hypovascular blood supply to hepatic artery implantation of the tumor in the test group A,comparing with that of the group B.Conclusion DSA can clearly display spacial details of the hepatic vascular anatomy in rabbits,and play an important role in post-procedual evaluation of the portal vein occlusion in rabbits.

OBJECTIVETo identify the anatomical variability of the left spermatic vein (LSV) and determine its effect on the induction of experimental left varicocele (ELV) in adolescent rats.

METHODSWe equally randomized 30 adolescent male SD rats to groups A (LSV collaterals fully ligated and the left renal vein constricted), B (only the left renal vein constricted), and C (sham operation), observed the courses of the LSVs and measured their diameters. At 30 days after operation, we analyzed the changes in the left kidneys and the diameters of the LSVs.

RESULTSIrregular collaterals were observed in 90% of the LSVs and no abnormal changes were found in the left kidneys after surgery. The postoperative LSV diameter was remarkably increased in group A as compared with the baseline ([1.47 +/- 0.15 ] vs [0.16 +/- 0.08] mm, P < 0.01), but showed no significant difference in group B ([0.31 +/- 0.49] vs [0.15 +/- 0.07] mm, P > 0.05) and C ([0.17 +/- 0.07] vs [0.16 +/- 0.06] mm, P > 0.05), and it was significantly longer in A than in B (P < 0.01). The success rate of ELV induction was 100% in group A and 10% in group B, but no varicocele was observed in group C.

CONCLUSIONCorrect identification of the anatomical course of the LSV and ligation of its irregular collaterals are essential for the establishment of a stable and consistent ELV model.

Animals ; Disease Models, Animal ; Kidney ; pathology ; Ligation ; Male ; Rats ; Rats, Sprague-Dawley ; Spermatic Cord ; blood supply ; Varicocele ; Veins ; abnormalities

To study the effect of pulchinenoside (PULC) on the Frizzled (FZD) expression of adjuvant arthritis ( AA) rats. AA rats were prepared through the toe injection with complete Freund's adjuvant to culture fibroblast-like synoviocytes (FLS). The effect of the oral administration with PULC on the FZD8 expression was detected by the real time qPCR. The effect of FZD8 knockout on the expressions of IL-1, IL-6, IL-8 were detected by MTT and ELISA. The role of miR-375 in the abnomal expression of FZD8 was detected by the real time qPCR. The results showed signfiicant decrease in the FZD8 expression among AA rats, FLS proliferation ater FZD8 knockout and IL-1, IL-6, IL-8 expressions and notable increase in miR-375 expression after the oral administration with PULC. The up-regulated miR-375 expression can inhibit the FZD8 expression. PULC may inhibit the FZD8 expression by up-regulating the miR-375 expression.
Animals ; Arthritis, Experimental ; drug therapy ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; genetics ; metabolism ; Saponins ; administration & dosage

Recent studies indicate that beta-amyloid (Abeta) is the key factor to cause neuronal degeneration in Alzheimer's disease (AD). In the present study, we set up an Abeta induced PC12 cell damage modle and studied the protective effect and related mechanisms of T(10), monomer extracted from Chinese herb Tripterygium wilfordii Hook F. PC12 cells were treated with different concentrations of Abeta (5x10(-4), 5x10(-3), 5x10(-2), 5x10(-1), 5, 50 micromol/L) for 48 h, cell viability was detected by MTT conversion. The apoptotic rate of PC12 cells was quantitatively determined using FACS assay. After PC12 cells were treated with 1x10(-11) mol/L T(10) for 48 h and then co-treated with 50 micromol/LAbetafor 48 h, the apoptotic rate and the change in intracellular Ca(2+) concentration of PC12 cells were analyzed by FACS assay and confocal, respectively. It was found that 5 micromol/L Abeta decreased the cell viability to 66.3% and 50 micromol/L Abeta decreased it to 55.1%, significantly different from that of the control group. After treatment with 50 micromol/L Abeta for 48 h, the apoptotic rate of PC12 cells increased obviously. The apoptotic rate was 5.37% in the control group, while after treatment with 0.5, 5 and 50 micromol/L Abeta for 48 h, the apoptotic rate of PC12 cells went up to 10.19%, 8.02% and 16.63%, respectively. At the same time, the concentration of intracellular Ca(2+) increased greatly after treatment with 50 micromol/L Abeta for 48 h. At the concentration of 1x10(-11) mol/L T(10) remarkably inhibited the apoptosis induced by 50 micromol/L Abeta. In the naive group, the apoptotic rate was 4.83%. The apoptotic rate went up to 17.24% after treatment with 50 micromol/L Abeta for 48 h. After co-treatment with 1x10(-11) mol/L T(10) and 50 micromol/L Abeta, the apoptotic rate decreased to 8.91%, significantly different from that of the control group. At the same time, at the concentration of 1x10(-11 )mol/L T(10) remarkably inhibited the increase of intracellular Ca(2+) concentration induced by Abeta. The results indicate that T(10) has obvious protective effect on PC12 cells, which may be related to the inhibition of the cell apoptosis and increment of intracellular Ca(2+) concentration induced by Abeta.
Alzheimer Disease ; pathology ; Amyloid beta-Peptides ; toxicity ; Animals ; Apoptosis ; drug effects ; Calcium ; metabolism ; Diterpenes ; pharmacology ; Epoxy Compounds ; Neuroprotective Agents ; pharmacology ; PC12 Cells ; Peptide Fragments ; toxicity ; Phenanthrenes ; pharmacology ; Rats ; Tripterygium ; chemistry

OBJECTIVETo explore evolution rules of phlegm and blood stasis syndrome ( PBSS) in hyperlipidemia and atherosclerosis (AS) using NMR-based metabolic profiling and metabonomic approaches based on formulas corresponding to syndrome.

METHODSTotally 150 SD rats were divided into the normal group, the model group, the Erchen Decoction (ED) group, the Xuefu Zhuyu Decoction (XZD) group, the Lipitor group, 30 in each group. The hyperlipidemia and AS rat model was duplicated by suturing carotid artery, injecting vitamin D3, and feeding with high fat diet. ED and XZD were used as drug probes. Blood samples were withdrawn at week 2, 4, and 8 after modeling. Blood lipids, blood rheology, histopathology and metabolomics were detected and analyzed. Results Results of blood lipids and pathology showed hyperlipidemia and early AS rat models were successfully established. At week 2 after modeling, levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) significantly increased, which reached the peak at week 4 and maintained at higher levels at week 8. ED exerted obvious effect in improving TC and LDL-C levels of early models, while XZD could greatly improve levels of TC and LDL-C of late models. Rheological results showed at week 2, there was no significant difference in whole blood viscosity, plasma viscosity, or hematocrit between the model group and the normal group (P > 0.05). At week 4 partial hemorheological indicators (such as plasma viscosity) were abnormal. Till week 8 whole blood viscosity, plasma viscosity, and hematocrit were significantly abnormal (P <0. 05, P < 0.01). As time went by, whole blood viscosity, plasma viscosity, and hematocrit showed gradual increasing tendency in the ED group, while they showed gradual decreasing tendency in the XZD group. Results of metabonomics showed significant difference in spectra of metabolites between the normal group and the model group. As modeling time was prolonged, contents of acetyl glucoprotein and glucose in the model group increased in late stage, which was in. line with results of blood lipids and hemorheology. ED showed more obvious effect in early and mid-term modeling (at week 2 and 4), and increased contents of partial metabolites (such as choline, phosphatidyl choline, glycerophosphocholine), but these changes in the XZD group were consistent with those of the model group. In late modeling (at week 8) XZD showed more obvious effect in improving contents of lactic acid, acetyl glycoprotein, LDL, creatine, choline, and glucose.

CONCLUSIONSED and XZD not only showed regulatory effects on lipid disorders, but also could improve dysbolism of Chos. In formulas corresponding to syndrome, damp-phlegm was main pathogenesis of hyperlipidema and AS in early and mid stages. Blood stasis syndrome began to occur along with it progressed. Phlegm can result in blood stasis and intermingles with stasis. Phlegm turbidity runs through the whole process.

Animals ; Atherosclerosis ; metabolism ; Cholesterol ; Cholesterol, LDL ; Drugs, Chinese Herbal ; therapeutic use ; Hemorheology ; Hyperlipidemias ; Lipids ; Magnetic Resonance Imaging ; Medicine, Chinese Traditional ; Metabolome ; physiology ; Metabolomics ; Rats ; Rats, Sprague-Dawley ; Sputum ; metabolism

OBJECTIVETo study on mechanisms of acupuncture in relieving visceral pain.

METHODSIn SD rats CRD was used as noxious visceral stimuli. Activities of spinal dorsal horn wide dynamic (WDR) neurons of L1-L13 were recorded by extracellular microelectrode technique. Acupuncture was given at ipsi-lateral and contra-lateral Zusanli (ST 36) of the same segmental innervation of rectum and colon.

RESULTSVisceral noxious afferent could significantly activate spinal dorsal horn convergent neurons, and mechanical stimulation of contra-lateral body surface and hand acupuncture at Zusanli (ST 36) could inhibit this noxious response. When the spinal cord was acutely blocked, the inhibiting CRD effect of needling CRD effect of needling contra-lateral Zusanli (ST 36) completely disappeared.

CONCLUSIONAcupuncture and visceral noxious afferent signals converge and interact each other in spinal level, and acupuncture at acupoint can inhibit the spinal dorsal horn neuron respon se activated by visceral noxious afferent and this action needs the participation of the center above the spinal cord.

Animals ; Colon ; innervation ; Nociceptors ; Posterior Horn Cells ; Rats, Sprague-Dawley ; Rectum ; Spinal Cord

A growing body of evidence suggests that p300 histone acetyltransferase plays important roles in cancer cell differentiation and proliferation. Here, we employed structure-based hierarchical virtual screening method to identify novel lead compounds of p300 histone acetyltransferase. From a screening library containing approximate 100 000 diverse druglike compounds, 33 compounds were chosen for experimental testing and one compound, 4-acetyl-2-methyl-N-morpholino-3,4-dihydro-2H-benzo[b][1, 4]thiazine-7-sulfonamide (17), showed as micromolar inhibitor. Based on its predicted binding pose, we investigated its binding characteristics by designing two series of structural modifications. The obtained structure-activity relationship results are consistent with the predicted binding model. We expect that the identified novel p300 histone acetyltransferase inhibitors will serve as starting points for further development of more potent and specific histone acetyltransferase inhibitors.
Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; Molecular Structure ; Morpholines ; chemical synthesis ; chemistry ; Structure-Activity Relationship ; Sulfonamides ; chemical synthesis ; chemistry ; p300-CBP Transcription Factors ; antagonists & inhibitors ; chemistry