The study reports the detection of neuroprotective effect of 10 kinds of coumarin derivatives and explores their possible mechanism. MTT method was used to screen the neuroprotective effect of 10 coumarin derivatives on neurotoxic agents (Aβ25-35 and rotenone) or OGD (oxygen-glucose deprivation). A compound with better protective effect was obtained. Then the effect of this compound on neurotoxic agents on PC12 was detected by the morphological observation. Furthermore, the effect of compound 3 on microglia with lipopolysaccharide (LPS) induced inflammation was detected. And the inflammatory factor was tested. Finally, direct free radical scavenging ability was detected. Compound 3 was found to be the best compound through three neurons toxic models. Not only compound 3 ameliorated cell viability reduced by three neurons toxic models, but also significantly inhibited the production of inflammatory factor (TNF-α and IL-1β). And its free radical scavenging ability is very good, especially the effect on superoxide anion, which is comparable with vitamin C. The significant scavenging effect of compound 3 on superoxide anion might be the mechanism of the neuroprotection. Compound 3 as a potential neural cell protective agent merits further investigation.
Animals ; Coumarins ; chemistry ; Free Radical Scavengers ; chemistry ; Inflammation ; Microglia ; drug effects ; Neurons ; drug effects ; Neuroprotective Agents ; chemistry ; PC12 Cells ; Rats

OBJECTIVETo evaluate the expression of nitric oxide synthase III (NOS III) mRNA in the heart, aorta, kidney and liver of spontaneously hypertensive rats (SHR).

METHODSTwo hundred and ninety-four total RNA samples were obtained from the tissues of ventricle, aortic smooth muscle, kidney and liver of SHR and normotensive rats (Wistar-Kyoto rats, WKY). RNA array was used to determine the mRNA levels of NOS III of the two groups.

RESULTSCompared with WKY, the systolic blood pressure increased significantly in SHR at 6-week-old, 8-week-old, 10-week-old and 12-week-old [(158.50 +/-7.69 vs 108.67 +/-5.89) mmHg, (174.33 +/-4.46 vs 128.50 +/-4.97) mmHg, (198.00 +/-13.45 vs 142.00 +/-3.58) mmHg, (216.67 +/-8.91 vs 141.17 +/-4.92) mmHg, P<0.01], and the ventricle/body weight ratio was significant higher at 10-week-old and 12-week-old [(4.08 +/-0.17 vs 3.59 +/-0.11, 4.05 +/-0.18 vs 3.40 +/-0.19)mg/g, P<0.01]. In the heart tissue and the kidney, the mRNA levels of NOS III were significantly increased at 6-week-old, 8-week-old, 10-week-old and 12-week-old (1.12 +/-0.18 vs 0.90 +/- 0.15, 1.46 +/- 0.34 vs 1.06 +/-0.18, 1.66 +/- 0.31 vs 1.21 +/- 0.30, 1.98 +/- 0.40 vs 1.31 +/-0.38, P <0.05) and at 4-week-old, 6-week-old, 8-week-old, 10-week-old and 12-week-old (1.10 +/- 0.21 vs 0.81 +/-0.11, 1.28 +/-0.18 vs 0.95 +/-0.13,1.31 +/-0.23 vs 0.99 +/-0.23, 1.70 +/-0.30 vs 1.08 +/-0.25, 1.83 +/-0.33 vs 1.15 +/-0.20, P<0.05 or P<0.01), respectively. There was no significant difference of the NOS III expression in the liver and no significant signals were detected in the aortic smooth muscle.

CONCLUSIONThe results provide the evidence of the increased expression of NOS III in different tissues in SHR and suggests the progressive nature of essential hypertension.

Animals ; Hypertension ; enzymology ; genetics ; Kidney ; enzymology ; Liver ; enzymology ; Male ; Myocardium ; enzymology ; Nitric Oxide Synthase ; biosynthesis ; genetics ; Nitric Oxide Synthase Type III ; Oligonucleotide Array Sequence Analysis ; methods ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY

Osteoclasts and osteoblasts are not exist alone,while communicating with each other through direct contact, diffusible paracrine factors and cell-bone matrix interaction. Co-culture system of osteoblast with osteoclast,including direct co-culture and indirect co-culture. It should be according to the ratio of osteoclasts and osteoblasts under the pathology, choosing the same species. Compared with lonely culture of osteoblasts or osteoclasts,co-culture system is much closer to the microenvironment in vivo. It benefits to explain the interactions between osteoblasts and osteoclasts, exploring molecular communication in bone diseases. It was mainly used to investigate the pharmacological mechanism of herbal and western medicine in bone remodeling. Some osteoporosis drugs (such as epimedium,sanchi, fructus psoraleae, ranelate strontium) not only promoted osteoblastic bone formation, but also inhibited osteoclastic bone resorption in the system,so as to balance bone homeostasis. At the same time,it has been used to study medical physics and assess biomedical materials in recent years. Considerably,the co-cultrue system will be used to study the subchondral bone remodeling and its pharmacological mechanism of herbal and western medicine in osteoarthritis.
Animals ; Bone Remodeling ; Cell Communication ; Coculture Techniques ; Humans ; Osteoblasts ; cytology ; Osteoclasts ; cytology

OBJECTIVETo examine the effect of particulate matter (PM) less than 10 microns in diameter (PM10) and ozone (O3) on daily mortality in Shanghai, China.

METHODSA generalized additive model with penalized spline function was used to observe the acute effect of PM10 and O3 on daily mortality.

RESULTSHigher PM10 significantly increased the effect of O3 on total mortality, and O3 also increased the effect of PM10 although the estimated increment was statistically insignificant.

CONCLUSIONOur findings provide further evidence for the effect of PM10 and O3 on daily mortality.

Air Pollutants ; toxicity ; China ; epidemiology ; Humans ; Mortality ; Ozone ; toxicity ; Urban Population

OBJECTIVETo evaluate the detection of cytomegalovirus (CMV) by polymerase chain reaction (PCR) for predicting the development of CMV disease.

METHODSOne hundred and thirty one allo-HSCT patients performed in the past 2 years were analyzed retrospectively. PCR-CMV was used to monitor CMV viremia and vireuria once a week after transplantation.

RESULTSIn the dynamic detection, CMV viremia was positive for at least one chance in 89 patients, vireuria did in 99 patients. Thirty-seven patients developed CMV disease with an accumulative incidence of 32.5%. The incidence of CMV disease was 15.6% in plasma CMV-PCR negative group, 31.3% in positive once group, and 47.3% in positive over twice group. There was significant difference among the three groups (P = 0.0126). The incidence of CMV disease was 24.8% in urine CMV-PCR negative group, 43.5% in positive once group, and 33.0% in positive over twice group, being no significant difference among them (P = 0.845). On analysis, viremia could predict the development of CMV disease: the PPV (positive predictive value) is 40.5%, NPV (negative predictive value) is 84.4%, sensitivity is 75.0%, and specificity is 69.2%.

CONCLUSIONSDetected by CMV-PCR, MCV viremia may predict the development of CMV disease, but MCV vireuria cannot.

Adolescent ; Adult ; Child ; Child, Preschool ; Cytomegalovirus ; genetics ; isolation & purification ; Cytomegalovirus Infections ; diagnosis ; etiology ; DNA, Viral ; blood ; urine ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; methods ; Retrospective Studies ; Sensitivity and Specificity ; Transplantation, Homologous ; adverse effects

This study is to explore the possible mechanisms of the antidepressant-like effect of agmatine. By using two traditional "behavior despair" model, tail suspension test and forced swimming test, we examined the effects of some monoamine receptor antagonists (including beta-adrenergic receptor antagonist propranolol, beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol, alpha2-adrenergic receptor antagonists yohimbine and idazoxan and 5-HT3 receptor antagonist tropisetron) on the antidepressant-like action of agmatine in mice. Activity of adenylate cyclase (AC) in the synapse membrane from rat frontal cortex was determined by radioimmunoassay. Single dose of agmatine (5-40 mg x kg(-1), ig) dose-dependently decrease the immobility time in tail suspension test in mice, indicating an antidepressant-like effect. The effect of agmatine (40 mg x kg(-1), ig) was antagonized by co-administration of beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol (20 mg x kg(-1), ip), alpha2-adrenergic receptor antagonists yohimbine (5-10 mg x kg(-1), ip) or idazoxan (4 mg x kg(-1), ip), but not beta-adrenergic receptor antagonist propranolol (5-20 mg x kg(-1), ip) and 5-HT3 receptor antagonist tropisetron (5-40 mg x kg(-1), ip). Agmatine (5-40 mg x kg(-1), ig) also dose-dependently decrease the immobility time in forced swimming test in mice. The effect of agmatine (40 mg x kg(-1), ig) was also antagonized by pindolol (20 mg x kg(-1), ip), yohimbine (5-10 mg x kg(-1), ip), or idazoxan (4 mg x kg(-1), ip). Incubation of agmatine (0.1-6.4 micromol x L(-1)) with the synaptic membrane extracted from rat frontal cortex activated the AC in a dose-dependent manner in vitro. While the effect of agmatine (6.4 micromol x L(-1)) was dose-dependently antagonized by pindolol (1 micromol x L(-1)) or yohimbine (0.25-1 micromol x L(-1)). Chronic treatment with agmatine (10 mg x kg(-1), ig, bid, 2 w) or fluoxetine (10 mg x kg(-1), ig, bid, 2 w) increased the basic activity, as well as the Gpp (NH)p (1-100 micromol x L(-1)) stimulated AC activity in rat prefrontal cortex. These results indicate that regulation on 5-HT1A/1B and alpha2 receptors, and activation AC in the frontal cortex is one of the important mechanisms involving in agmatine's antidepressant-like action.
Adenylyl Cyclases ; metabolism ; Adrenergic alpha-Antagonists ; pharmacology ; Adrenergic beta-Antagonists ; pharmacology ; Agmatine ; administration & dosage ; pharmacology ; Animals ; Antidepressive Agents ; administration & dosage ; pharmacology ; Behavior, Animal ; drug effects ; Depression ; metabolism ; physiopathology ; Dose-Response Relationship, Drug ; Fenclonine ; pharmacology ; Idazoxan ; pharmacology ; Male ; Mice ; Pindolol ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Biogenic Amine ; antagonists & inhibitors ; Serotonin 5-HT1 Receptor Antagonists ; Swimming ; Synapses ; enzymology ; Yohimbine ; pharmacology

Objective To establish a PD model of overexpressing rat c-Jun N-terminal kinase 3 (JNK3) in SHSYSY(SHSYSY-rJNK3), and study the relationship between JNK3 and occuring of PD and AD. Methods Extract purificat RNA and get Rat JNK3 through RT-PCR. The pcDNA3. L/hisC-rJNK3 vector was established and stably transfected into SHSY5Y overexpressing rat JNK3. SHSYSY-rJNK3 was selected by Western blotting analysis. The growth rate and the sensitivity to MPI+ of SHSY5Y-rJNK3 were further evaluated by morphological observation, immunofluorescence and MTT assay. Results Successfully established SHSY5Y-rJNK3 series by transfeeted pcDNA3.1/hisC-rJNK3 vector in SHSY5Y over expressing rJNK3. There were morphological differences between SHSY5Y and SHSY5Y-rJNK3. The result of MTT showed that there were little differences between growth rate of both. Stimulated by MPP+ of different concentrations, the SHSY5Y-rJNK3 made more morphological changes in 100 um MPP+ than SHSYSY, and the results of MTT also demonstrated that SHSY5Y-rJNK3 was more sensitive to MPP+ compared to SHSYSY with lower cell viability. Conclusions Overexpressing JNK3 in SHSY5Y makes morphological changes on cells, also makes cells more sensitive to the poisons. Therefore, studying on SHSYSY-rJNK3 which is overexpressed JNK3 can reflect phenomenons and substance of apotosis which related to JNK3 more objective and accurately.

OBJECTIVETo explore the incidence, prognosis and risk factors of the acute graft versus host disease (aGVHD) after allo-hematopoietic stem cell transplantation (allo-HSCT).

METHODSThe clinical data of 118 cases undergone 120 times of allo-HSCT were analyzed.

RESULTaGVHD was observed in 63 cases (52.57%) including 17 severe cases (14.17%). The patients with aGVHD had a poor outcome, the 2-year overall survival rates were 61.40%, 64.08% and 17.65% for the non aGVHD, mild (degree I-II) and severe (degree III-IV) aGVHD groups respectively (P < 0.01). However, the relapse rates were 12.48%, 20.53% and 0% with no statistic significance. Unrelated transplantation and HLA-mismatch were the risk factors for aGVHD.

CONCLUSIONaGVHD is a common complication after allo-HSCT, the earlier it takes place, the poorer the prognosis.

Acute Disease ; Adolescent ; Adult ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Graft vs Host Disease ; epidemiology ; etiology ; pathology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Incidence ; Male ; Middle Aged ; Prognosis ; Risk Factors ; Severity of Illness Index ; Survival Analysis ; Time Factors ; Transplantation, Homologous

OBJECTIVETo investigate the relation between air pollution exposure and preterm birth in Shanghai, China.

METHODSWe examined the effect of ambient air pollution on preterm birth using time-series approach in Shanghai in 2004. This method can eliminate potential confounding by individual risk factors that do not change over a short period of time. Daily numbers of preterm births were obtained from the live birth database maintained by Shanghai Municipal Center of Disease Control and Prevention. We used the generalized additive model (GAM) with penalized splines to analyze the relation between preterm birth, air pollution, and covariates.

RESULTSWe observed a significant effect of outdoor air pollution only with 8-week exposure before preterm births. An increase of 10 microg/m3 of 8-week average PM10, SO2, NO2, and O3 corresponded to 4.42% (95%CI 1.60%, 7.25%), 11.89% (95%CI 6.69%, 17.09%), 5.43% (95%CI 1.78%, 9.08%), and 4.63% (95%CI 0.35%, 8.91%) increase of preterm birth. We did not find any significant acute effect of outdoor air pollution on preterm birth in the week before birth.

CONCLUSIONAmbient air pollution may contribute to the risk of preterm birth in Shanghai. Our analyses also strengthen the rationale for further limiting air pollution level in the city.

Air Pollutants ; adverse effects ; Air Pollution ; adverse effects ; China ; epidemiology ; Female ; Humans ; Infant, Newborn ; Pregnancy ; Premature Birth ; epidemiology ; etiology

This study was aimed to investigate the clinical outcome of ricin-immunotoxin mediated T cell partially depleted HLA/MLC mismatched allogeneic hematopoietic stem cell transplantation. 13 patients with hematological malignancies were treated by ricin-immunotoxin mediated T cell partially depleted allogeneic hematopoietic stem cell transplantations from HLA/MLC mismatched donors, including 6 cases of CML in CP(1), 1 case of ALL in CR(1), 1 case of ALL in CR(2), 1 case of ALL in relapse, 2 cases of AML in CR(1), 1 case of AML in CR(2), 1 case of MDS-RAEBT-AML (M(4)) in CR(1). The results showed that 8 cases were engrafted successfully, 2 cases of them developed grade II acute GVHD and 2 cases developed grade III-IV acute GVHD. Within following-up of 8 - 90 months, 2 patients who experienced grade III-IV acute GVHD died early after transplantation; 1 patient died of late onset of infection; the other 5 patients survived free from diseases. After failure at first infusion, 4 patients were given reinfusion of peripheral blood hematopoietic stem cells from the same donor. 3 out of 4 cases failed to engraft and only one patient got engraftment but died of related complications of transplantation. One patient was performed a second transplantation from a syngeneic donor and survive free of disease until now. In conclusion, T cell partially depleted HLA/MLC mismatched allogeneic hematopoietic stem cell transplantation by ricin-immunotoxin decreases the occurrence of severe acute GVHD but with high risk of rejection, which clinical outcome still needs further evaluation.
Adolescent ; Adult ; Child ; Female ; Graft vs Host Disease ; epidemiology ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; mortality ; Humans ; Immunotoxins ; pharmacology ; Lymphocyte Depletion ; methods ; Male ; Ricin ; pharmacology ; T-Lymphocytes ; drug effects ; Transplantation, Homologous