Animals ; Antidepressive Agents ; pharmacology ; Brain-Derived Neurotrophic Factor ; metabolism ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Depression ; metabolism ; pathology ; physiopathology ; Hippocampus ; metabolism ; pathology ; physiopathology ; Humans ; Nerve Degeneration ; physiopathology ; Nerve Regeneration ; drug effects ; Neurons ; pathology ; Stress, Psychological ; metabolism ; pathology ; physiopathology

OBJECTIVETo study the possible mechanism of aqueous extract of detoxified cottonseeds (CTN-W).

METHOD AND RESULTCTN-W 0.01, 0.03, 0.10, 0.30 mg.mL-1 was incubated directly with the synaptic membrane extracted from the cerebral cortex in rats, and adenylyl cyclase (AC) activity was detected by using radio-immunoassay.

RESULTShowed that CTN-W could activate AC in a dose-dependend manner. After incubation with PC12 cells in the presence of corticosterone 2 x 10(-4)mol.L-1 for 48 h, CTN-W 0.08, 0.4, 2 mg.mL-1 protected PC12 cells from the lesion induced by corticosterone.

CONCLUSIONAntidepressant and anxiolytic effects of CTN-W are related with the activation of AC-cAMP pathway in signal transduction system, thus protecting neurons from the lesion. These two aspects maybe partly form the mechanism of CTN-W's action.

Adenylyl Cyclases ; metabolism ; Animals ; Anti-Anxiety Agents ; pharmacology ; Antidepressive Agents ; pharmacology ; Corticosterone ; antagonists & inhibitors ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Gossypium ; chemistry ; Neuroprotective Agents ; pharmacology ; PC12 Cells ; drug effects ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar ; Seeds ; chemistry ; Synaptic Membranes ; enzymology

BACKGROUNDXiaobuxin-Tang, a traditional Chinese herbal prescription recorded in a silk scroll unearthed from Mogao Caves of Dunhuang has been indicated that it can remit depressive disorder. The present study was designed to investigate its antidepressant effects in various animal depression models.

METHODSXiaobuxin-Tang was extracted by 70% alcohol, and then three behavioral despair models and 5-Hydroxytryptophan (HTP)-induced head twitch response model were adopted to assess the antidepressant effects of the ethanolic extract of Xiaobuxin-Tang with the study on spontaneous motor activity. Groups of mice and rats received oral treatment with Xiaobuxin-Tang (150 - 1200 mg/kg) only once acutely in all tests. The duration of immobility was measured during the last 4 minutes of the 6-minutes test period in mice forced swimming test, rats forced swimming test and mice tail suspension test. In 5-HTP-induced head twitch response, the mice were intraperitoneally administered with 120 mg/kg of L-5-HTP, and then the cumulative number of head twitches was counted in 20 minutes. Spontaneous motor activities of mice were recorded automatically in 10 minutes by VIDEOMEX-V image analytic system.

RESULTSThe extract at doses of 300 mg/kg (p.o.) and 600 mg/kg (p.o.) significantly decreased the duration of immobility time in a dose dependent manner in mice forced swimming test; also, the extract at dose of 1200 mg/kg (p.o.) significantly decreased the duration of immobility time in rat forced swimming test. Furthermore, the extract at a dose of 600 mg/kg had the same effect in mice tail suspension test. Meanwhile, the extract at the effective doses for behavioral despair models, had no effect on spontaneous motor activity in mice. The extract (300 - 1200 mg/kg, p.o.) also increased the accumulative number of the 5-HTP-induced head twitch response in mice in 20 minutes.

CONCLUSIONOur results suggested that the ethanolic extract of Xiaobuxin-Tang exerts antidepressant-like effect.

Animals ; Antidepressive Agents ; pharmacology ; Depression ; drug therapy ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Hindlimb Suspension ; Male ; Mice ; Mice, Inbred ICR ; Motor Activity ; drug effects ; Swimming

BACKGROUNDAccumulating evidence demonstrates that the microenvironment of the host has an important effect on the chemoresistance of tumors. We also found that the formation of intrinsic multidrug resistance is related to environmental factors that are common with tumor growth of hepatocellular carcinoma. The aim of this study was to explore the molecular mechanisms by which multidrug resistance of hepatocellular carcinoma is induced by the microenvironment. In particular, the regulation of nuclear transcription factor (hypoxia-inducible factor-1α, HIF-1α) activation in the process of multidrug resistance formation was investigated.

METHODSHepG2 cells were exposed to different microenvironmental conditions respectively, such as hypoxia, stimulation of glucose deprivation and transfection of plasmid PcDNA3/HBx. In the HepG2 cells, the expression of the related MDR proteins, HIF-1α protein expression and localization, activity of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) were detected. Specific inhibitor U0126 was used to block ERK/MAPK signal pathway, the alteration of HIF-1α and the related MDR proteins were investigated. Multivariate analysis of variance (MANOVA) repeated measures and one-way analysis of variance (ANOVA) followed by Tukey test or t-test were used to determine differences over time and effects of the treatments.

RESULTSThe above three microenvironment factors increase the expression of the related MDR proteins (including P-gp, LRP, and MRP1) and induce MDR of HepG2 cells. HIF-1α was induced at the protein and mRNA levels and the nuclear translocation was also increased. The activity of ERK/MAPK was also increased in HepG2 cells. But when ERK/MAPK pathway was inhibited, the mRNA and protein expression of MDR1, MRP1, and LRP was to some extent decreased. Inhibition of ERK/MAPK significantly reduced activated HIF-1α protein and the nuclear translocation of HIF-1α, whereas HIF-1α mRNA levels were not affected.

CONCLUSIONSThe microenvironmental factors could induce MDR of HepG2 cells by the activity of HIF-1α. The activity of HIF-1α is regulated by the ERK/MAPK pathway at the phosphorylation level. As an important nuclear transcription factor, HIF-1α controls the transcription of MDR-related genes and the synthesis of their corresponding proteins by ERK/MAPK signal pathway in HepG2 cells.

Drug Resistance, Neoplasm ; Hep G2 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; physiology ; MAP Kinase Signaling System ; Tumor Microenvironment

To discuss the effects on early warning of measles, using the neural networks.Based on the available data through monthly and weekly reports on measles from January 1986 to August 2006 in Wuhan city. The modal was developed using the neural networks to predict and analyze the prevalence and incidence of measles. When the dynamic time series modal was established with back propagation(BP) networks consisting of two layers, if p was assigned as 9, the convergence speed was acceptable and the correlation coefficient was equal to 0.85. It was more acceptable for monthly forecasting the specific value, but better for weekly forecasting the classification under probabilistic neural networks (PNN). When data was big enough to serve the purpose, it seemed more feasible for early warning using the two-layer BP networks. However, when data was not enough, then PNN could be used for the purpose of prediction. This method seemed feasible to be used in the system for early warning.

OBJECTIVES: To explore the correlation between cytosine-phosphoric-guanylic (CpG) site of Septin 9 gene and colorectal cancer, and to develop a real-time PCR detection system in plasma in patients with colorectal cancer. METHODS: The methylation of training samples was detected by high-throughput sequencing technology, and the sites highly consistent with the clinical information of colorectal cancer were identified. Then the detection system of real-time PCR was designed to analyze the consistency of plasma and tissue based on methylationa sensitive enzyme digestion. Finally, 100 clinical trials were conducted to evaluate the performance of the detection system with the methylation sensitive enzyme digestion-real-time PCR. RESULTS: The highly consistent sites, which were selected by high-throughput sequencing from 71 training set samples, was the 38th CpG. Based on the detection region, the screened methylation sensitive enzymes were CONCLUSIONS The 38th CpG site of Septin 9 detected by the detection system of methylation sensitive enzyme digestion-real-time PCR can highly predict the occurrence of colorectal cancer with great clinical application value.
Colorectal Neoplasms/genetics* ; CpG Islands/genetics* ; DNA ; DNA Methylation ; Humans ; Plasma/metabolism* ; Septins/metabolism*

OBJECTIVETo study the relationship between serum iron(SI) and essential hypertension (EHT) based on population-based samples.

METHODSUsing clustering multistage sampling method, all the people above 18 years old in the target population were investigated. Blood pressure was measured and the questionnaire was used to find out related factors. Five milliliters fast vein blood were drawn and the serum were used for testing on serum iron (SI) and other elements such as blood sugar, cholesterol (CHOL), triglyceride (TG), high density lipoprotein(HDL-C), low density lipoprotein (LDL-C), serum sodium, serum potassium, serum calcium etc. A case control study was carried out with EHT patients from the selected population as case group, and the other healthy peoples as controls. Database was created by Fox Pro and SPSS 10.0 was used for statistical analysis.

RESULTSThe concentrations of SI, with (17.75 +/- 7.66) micromol/ L in EHT group and (17.23 +/- 7.83) micromol/L in control group, showed statistical difference (P < 0.05) between the two groups. The concentrations of SI also showed statistical difference (P < 0.05) between the high DBP and normal group with the average level as (17.84 +/- 7.58) micromol/L in high DBP group and (17.26 +/- 7.85) micromol/L in normal group. Data from monovariate analysis showed that the increase of SI was a risk factor for EHT, DBP and SBP. By multivariate analysis for EHT, while SI still existed in the model (OR = 1.296, 95% CI: 1.057-1.590), but for SBP the results almost remained the same (OR = 1.285, 95% CI:1.102-1.498).

CONCLUSIONData from the results showed that SI was probably a risk factor for EHT.

Case-Control Studies ; China ; epidemiology ; Humans ; Hypertension ; blood ; epidemiology ; Iron ; blood ; Risk Factors

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Wilt disease is a major disease of cultivated Salvia miltiorrhiza, which is caused by Fusarium oxysporum. Since the infection process of F. oxysporum in plants is affected by environment factors, this study was conducted to reveal the relationship between disease severity and concentration of the pathogen in plants in the infection process of F. oxysporum in seedlings of S. miltiorrhiza by pot experiments and to reveal the effects of temperature and humidity on the infection process. The results showed that, after inoculation of S. miltiorrhiza seedlings with F. oxysporum, the pathogen in different parts was detected at different time, and it was first detected in substrates. With the continuous propagation of the pathogen(4-5 d), it gradually infected the roots and stems of the seedlings, and the plants had yellowing leaves and withering. The number of the pathogen reached the maximum in each part after 7-8 d, and then gradually decreased in the later stage of the disease. The concentration of the pathogen in substrates, roots and stems of S. miltiorrhiza showed a trend of decreasing after increasing with the aggravation of the disease and reached the maximum in the samples of moderate morbidity, while the concentration in the samples of severe morbidity decreased. In addition, the infection of F. oxysporum in seedlings of S. miltiorrhiza was affected by temperature and humidity. The suitable temperature was 25-30 ℃ and the suitable humidity was 80%-90%. This study could provide guidance for the experiments on pathogenicity of F. oxysporum, screening of biocontrol bacteria and controlling of wilt.
Seedlings/microbiology* ; Salvia miltiorrhiza ; Temperature ; Humidity ; Fusarium

Objective:To observe the effect of serum of kidney Yang deficiency rats on the expression of β-catenin，osteoprotegerin(OPG) and nuclear transcription factor-κB receptor activator ligand (RANKL) in the co-culture system and regulatory of icariin on it， and to explore the possible mechanism of inducing osteoporosis.Method:The 16 male SD rats were randomly divided into blank group and model group， 8 rats in each group. 10 mL·kg^-1 adenine was administrated to stomach to establish kidney yang deficiency model. Serum was separated and extracted after the model was established successfully. Isolation and culture of osteoblast（OB） and osteoclast（OC） in vitro， OB was observed and identified by alkaline phosphatase（ALP），alizarin red and Giemsa staining， OC was identified by tartrate resistant acid phosphatase（TRAP） staining， OB-OC co-culture system was established in transwell cell， icariin group（100 μmol·L^-1）， blank group， icariin（100 μmol·L^-1） + serum group， serum group and Dickkopf1（DKK-1） drug（100 μg·L^-1） were set up in group ， 2 days after intervention of co-culture system， OC was counted， ALP and TRAP in supernatant were detected by microplate enzyme labeling， and the expression of OPG，β-catenin and RANKL in each group was detected by Western blot.Result:Compared with blank group， the ALP activity，β-catenin and OPG protein expression in serum group were significant reduction （P<0.05）， while the OC quantity， TRAP activity and RANKL protein expression were marked increase （P<0.05）. Compared with serum group， ALP activity of icariin group decreased significantly （P<0.01）， Compared with icariin group， ALP activity and OPG protein expression decreased （P<0.05）， trap activity and RANKL expression increased （P <0.05） in icariin + serum group.Conclusion:The serum of kidney Yang deficiency rats can induce the occurrence of osteoporosis， and the mechanism of action may be through inhibition of ALP activity， down regulating the expression of β-catenin and OPG protein， increasing the activity of TRAP and the expression of RANKL protein.