OBJECTIVETo explore the intersection and regulation mechanism of "efficacy-toxicity network" of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata's action gene in the combination environment of Sini decoction with the network pharmacological method.

METHODThe gene interaction network of Aconiti Lateralis Radix Praeparata, Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma were mined and established with Cytoscape software and Agilent literature search plug-in. The "efficiency-toxicity network" intersection of Aconiti Lateralis Radix Praeparata was formed according to its effects in anti-heart failure, neurotoxicity and cardiotoxicity. The target genes were clustered with Clusterviz plug-in. And the possible pathways of the "efficacy-tox- icity network" intersection of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata were forecasted in DAVID database.

RESULTThere were five genes related to neurotoxicity, cardiotoxicity and anti-heart failure function of Aconiti Lateralis Radix Praeparata, namely AKT1, BAX, HCC, IL6 and IL8, which formed 47 nodes genes in the "efficiency-toxicity network" intersection of Aconiti Lateralis Radix Praeparata. There were 29 and 27 coincident genes in the "efficiency-toxicity network" of Glycyrrhizae Radix et Rhizoma, Zingiberis Rhizoma and Aconiti Lateralis Radix Praeparata. There were 23 and 17 possible regulatory pathways.

CONCLUSIONIn the combination environment of Sini decoction, Glycyrrhizae Radix et Rhizoma and Zingiberis Rhizoma may regulate the efficiency-toxicity network of Aconiti Lateralis Radix Praeparata by influencing immune-inflammatory signaling pathway, apoptosis-autophagy signaling pathway, nerve cell and myocardial ischemia and hypoxia protection signaling pathways.

Aconitum ; chemistry ; toxicity ; Drugs, Chinese Herbal ; chemistry ; toxicity ; Gene Regulatory Networks ; drug effects ; Humans ; Rhizome ; chemistry ; toxicity

Carbon source plays an important role in the constitutive expression of foreign proteins in Pichia pastoris. In present study, glucose , glycerol , methanol and oil acid, was used respectively as the only carbon source to constitutively express hAS in Pichia pastoris GS115 (pGAP9K-AS)in shaking flask. The result shows that oleic acid is the best (163 mg/L) compared with glycerol (83mg/L), glucose (76 mg/L)and methanol (57 mg/L). Since oleic acid is insoluble in water, glycerol was used as the carbon source in the high-density cell culture of GS115 (pGAP9K-AS) in a 30 liter bioreactor and 169 mg/L of angiostatin was obtained after 48h of culture. The expressed angiostatin is immunologically active as shown by Western blotting. The recombinant hAS inhibits bFGF induced CAM angiogenesis and suppresses the growth of B16 melanoma in C57BL/6J mice. The tumor inhibition rate is 90% after 12 days of treatment. Statistics analysis revealed that the tumor volume difference of mice between the hAS group and PBS group is prominent (P < 0.01).
Angiogenesis Inhibitors ; biosynthesis ; genetics ; therapeutic use ; Angiostatins ; biosynthesis ; genetics ; therapeutic use ; Animals ; Bioreactors ; microbiology ; Culture Media ; pharmacology ; Fermentation ; Glycerol ; pharmacology ; Humans ; Melanoma, Experimental ; drug therapy ; Mice ; Mice, Inbred C57BL ; Pichia ; genetics ; growth & development ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; therapeutic use

OBJECTIVETo investigate the brain oxidative stress injury induced by nano-alumina particles in ICR mice.

METHODSSixty male ICR mice were randomly divided into 6 groups: control group, solvent control group, 100 mg/kg micro-alumina particles group, 3 groups exposed to nano-alumina particles at the doses of 50, 100 and 200 mg/kg. The mice were exposed by nasal drip for 30 days. Then levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) in brain tissues of mice were detected.

RESULTSThere was no difference of SOD activity in mouse brain between control group [(17.32 +/- 6.23)U/gHb] and 50 mg/kg nano-alumina particles group [(17.89 +/- 1.82) U/gHb]. The SOD activity [(4.93 +/- 2.30)U/gHb] in 200 mg/kg nano-alumina particles group was significantly lower than that in control group (P < 0.05). The MDA levels in 3 nano-alumina particles groups were (0.76 +/- 0.13), (1.00 +/- 0.30) and (1.16 +/- 0.39)nmol/ml, respectively, which were significantly higher than that [( 0.24 +/- 0.09)nmol/ml] in control group (P < 0.05). The GSH levels in 3 nano-alumina particles groups were (0.72 +/- 0.08), (0.55 +/- 0.19) and (0.61 +/- 0.20)mg/gpro, respectively, which were significantly lower than that [(1.55 +/- 0.34)mg/gpro]] in control group (P < 0.05). The CAT activity in 50 and 100 mg/kg nano-alumina particles groups were (10.40 +/- 3.84) and (10.40 +/- 2.00)U/mgpro, respectively, which were significantly higher than that [(5.79 +/- 0.96) U/mgpro] in control group (P < 0.05). The CAT activity [(3.25 +/- 1.04)U/mgpro] in 200 mg/kg nano-alumina particles group was significantly lower than that in control group (P < 0.05 ).

CONCLUSIONNano-alumina particles can induce the oxidative stress damage in brain tissues of mice.

Aluminum Oxide ; toxicity ; Animals ; Cerebral Cortex ; metabolism ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred ICR ; Nanoparticles ; toxicity ; Oxidative Stress ; Superoxide Dismutase ; metabolism

BACKGROUNDHepatitis B virus infection is closely related to hepatocellular carcinoma (HCC). Cyclooxygenase-2 (COX-2) is overexpressed in HCC and considered to play a role in hepatic carcinogenesis. In this study, we analyzed the polymorphism of COX-2 promoter -899G/C in healthy controls, chronic hepatitis B (CHB) patients, liver cirrhosis patients, and hepatocellular carcinoma (HCC) patients, to investigate the relationship between COX-2 -899G/C polymorphism and the risk for hepatitis B-related liver cancer in a Chinese population from Gansu province.

METHODSPatients were divided into four groups: 300 patients with CHB, 300 patients with liver cirrhosis, 300 patients with HCC, and 300 healthy controls. The polymorphism of COX-2 -899G/C was detected by PCR-TaqMan probes. The results were analyzed by SPSS 17.0.

RESULTSThe COX-2 -899G/C genotypes were GG, GC, and CC. Frequencies in CHB were 87.00%, 12.67%, 0.33%; in liver cirrhosis were 85.33%, 14.00%, 0.67%; in HCC were 77.00%, 21.67%, 1.33%; and in healthy controls were 90.67%, 9.00%, 0.33%, respectively. COX-2 -899C carriers may have an increased risk for hepatitis B-related liver cancer. Compared with the frequency of GG genotype, there were significant differences in the frequency of GC genotype between HCC and healthy control groups (OR = 2.835, 95%CI: 1.751 - 4.589); HCC and CHB groups (OR = 1.933, 95%CI: 1.248 - 2.994); and HCC and liver cirrhosis groups (OR = 1.175, 95%CI: 1.119 - 2.628). Stratification analyses showed that COX-2 -899C allele carriers with a drinking history are more susceptible to develop HCC.

CONCLUSIONCOX-2 -899C genotype may increase the susceptibility of individuals to hepatitis B-related liver cancer in Gansu province, China.

Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Carcinoma, Hepatocellular ; etiology ; genetics ; Cyclooxygenase 2 ; genetics ; Female ; Genetic Predisposition to Disease ; Hepatitis B ; etiology ; genetics ; Humans ; Liver Neoplasms ; etiology ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; genetics ; Promoter Regions, Genetic ; genetics

AIMTo explore the effects of periphery injection of L-SOP on the activation of p38MAPK in spinal cord in formalin pain model in rats.

METHODSFourty-eight male Wistar rats were divided randomly into four groups (n=12): NS group and three different dose of L-SOP groups. For each group, 6 rats used to observe flinching and licking time every as nociception behavior 3 minutes in 1 hour after formalin injected and the other 6 rats used to observe the activation of p38(P-p38) by Western blotting.

RESULTSAll the three different groups of L-SOP could inhibit nociception behavior in the tonic phase,and 250 nmoVl/L and 500 nmol/L groups could suppress not only in the tonic phase but also in the acute phase. 250 nmol/L and 500 nmol/L groups could reduce activated or phosphorylated p38MAPK in spinal cord.

CONCLUSIONPeriphery injection of L-SOP can reduce nociceptive behavior and phosphorylated p38MAPK in the spinal cord in formalin-induced hyperalgia, it is suggested that there is functional expression of mGluRs III in the periphery and is involved in the processing of peripheral noxious informations.

Animals ; Formaldehyde ; Male ; Nociception ; physiology ; Pain ; chemically induced ; metabolism ; physiopathology ; Phosphoserine ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Metabotropic Glutamate ; physiology ; Spinal Cord ; metabolism ; physiopathology ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objective To investigate the expression and clinical significance of excision repair cross complementing gene 1 (ERCC1 )in colorectal carcinoma of stage Ⅱ and its clinical significance.Methods We collected 56 cases of stage Ⅱ postoperative colorectal carcinoma tissue and detected ERCC1 expression with immunofluorescence technique.Statistical analysis was made with SPSS13.0 software.Results ERCC1 expression was obviously lower in stage II postoperative colorectal carcinoma tissue than in normal tissue (P =0.01).In cancer tissue,ERCC1 expression in patients with relapse or metastasis was significantly lower than in those without (P =0.002);ERCC1 expression in patients with T3 was significantly higher than those with T4 (P = 0.044).ERCC1 expression had a positive correlation with the overall survival (OS)and disease-free survival (DFS)(both P =0.000).In the group of high ERCC1 expression patients,five-year OS rate and DFS rate between patients who had received oxaliplatin-based adjuvant chemotherapy and those who did not have no significant difference (P =0.351;P =0.465).In the group of low ERCC1 expression patients,five-year OS rate and DFS rate of patients who received oxaliplatin-based adjuvant chemotherapy were significantly higher than those of patients who did not (P =0.015,P =0.02).ERCC1 (P =0.031 )and relapse or metastasis (P =0.009)were independent factors affecting OS;relapse or metastasis (P =0.000)was an independent factor affecting DFS.Conclusion ERCC1 is an independent factor affecting the OS of patients with stage Ⅱ colorectal carcinoma.Patients with low ERCC1 expression have poor prognosis,but they can benefit from oxaliplatin-based adjuvant chemotherapy.

Objective To predict the monthly reported echinococcosis cases in China with the autoregressive integrated mov-ing average(ARIMA)model,so as to provide a reference for prevention and control of echinococcosis. Methods SPSS 24.0 software was used to construct the ARIMA models based on the monthly reported echinococcosis cases of time series from 2007 to 2015 and 2007 to 2014,respectively,and the accuracies of the two ARIMA models were compared. Results The model based on the data of the monthly reported cases of echinococcosis in China from 2007 to 2015 was ARIMA(1,0,0)(1,1, 0)12,the relative error among reported cases and predicted cases was-13.97%,AR(1)=0.367(t=3.816,P<0.001),SAR (1)=-0.328(t=-3.361,P=0.001),and Ljung-Box Q=14.119(df=16,P=0.590).The model based on the data of the monthly reported cases of echinococcosis in China from 2007 to 2014 was ARIMA(1,0,0)(1,0,1)12,the relative error among reported cases and predicted cases was 0.56%,AR(1)=0.413(t=4.244,P<0.001),SAR(1)=0.809(t=9.584, P<0.001),SMA(1)=0.356(t=2.278,P=0.025),and Ljung-Box Q=18.924(df=15,P=0.217).Conclusions The different time series may have different ARIMA models as for the same infectious diseases.It is needed to be further verified that the more data are accumulated,the shorter time of predication is,and the smaller the average of the relative error is.The estab-lishment and prediction of an ARIMA model is a dynamic process that needs to be adjusted and optimized continuously accord-ing to the accumulated data,meantime,we should give full consideration to the intensity of the work related to infectious diseas-es reported(such as disease census and special investigation).

This study was aimed to discuss and analyze the medication rules for prescriptions containing Pterocephali Herba in Chinese Medical Encyclopedia - Tibetan Medicine, Tibetan Medicine Prescription Modern Research and Clinical Application, and Interpretation of Common Tibetan Medicines based on the collection of Pterocephali Herba and by using the "Traditional Chinese Medicine Inheritance Support system(V2.0.1)",with the use of association rules, apriori algorithm and other data mining methods. The frequency of single drug, the frequency of drug combination, the association rule and the combination of core drugs were analyzed. Through collection of the prescriptions, a total of 215 prescriptions were included, involving a total of 376 herbs. Through the "frequency statistics", the prescriptions containing Pterocephali Herba were commonly used to treat cold fever, distemper virus and arthritis. The highest frequently (frequency≥15) used drugs were Corydalis Herba, Lagotidis Herba, and Gentianae Macrophyllae Radix, et al. The most frequently used drug combinations were "Pterocephali Herba, Corydalis Herba","Pterocephali Herba, Lagotidis Herba", and "Pterocephali Herba, Gentianae Macrophyllae Radix" et al. The prescriptions containing Pterocephali Herba were used to primarily treat disease for Tourette syndrome caused by the dampness heat toxin, fever, arthritis etc, such as pestilent toxicity, pneumonia and influenza, rheumatoid arthritis etc. The drugs in the prescriptions mostly had the effects of heat-clearing and detoxifying, anti-inflammatory, dispelling wind and dampness, often in compatible use with heat-clearing drugs. The drug use was concentrated and reflected the clear thought of prescription statutes.

Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF/MS) was used to investigate the effect of Pterocephalus hookeri on serum metabolism of adjuvant arthritis(AA) model rats induced by complete Freund's adjuvant. After the AA model was properly induced, the serum of rats was collected 30 days after treatment. UPLC-Q-TOF-MS chromatograms were collected and analyzed by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The results revealed that compared with the control group, the model group showed increased content of 12 biomarkers in the serum(P<0.05) and reduced content of the other nine biomarkers(P<0.05). P. hookeri extract could recover the above-mentioned 19 biomarkers to a certain range. Pathway enrichment showed that these markers mainly involved eight metabolic pathways, including valine, leucine, and isoleucine degradation, arachidonic acid metabolism, arginine and proline metabolism, glycerol phospholipid metabolism, primary bile acid biosynthesis, bile acid biosynthesis, tryptophan metabolism, and unsaturated fatty acid biosynthesis. The findings of this study demonstrate that P. hookeri extract can regulate metabolic disorders and promote the regression of metabolic phenotype to the normal level to exert the therapeutic effect on AA rats. This study is expected to provide a certain scientific basis for the biological research on the treatment of rheumatoid arthritis by P. hookeri.
Animals ; Arthritis, Rheumatoid/drug therapy* ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Tibetan Traditional ; Metabolomics ; Rats

BackgroundRisperidone and paliperidone have been the mainstay treatment for schizophrenia and their potential role in neuroprotection could be associated with brain-derived neurotrophic factor (BDNF) and N400 (an event-related brain potential component). So far, different effects on both BDNF and N400 were reported in relation to various antipsychotic treatments. However, few studies have been conducted on the mechanism of risperidone and paliperidone on BDNF and N400. This study aimed to compare the effects of risperidone and paliperidone on BDNF and the N400 component of the event-related brain potential in patients with first-episode schizophrenia.

MethodsNinety-eight patients with first-episode schizophrenia were randomly divided into the risperidone and paliperidone groups and treated with risperidone and paliperidone, respectively, for 12 weeks. Serum BDNF level, the latency, and amplitude of the N400 event-related potential before and after the treatment and Positive and Negative Syndrome Scale (PANSS) scores were compared between the two groups.

ResultsA total of 94 patients were included in the final analysis (47 patients in each group). After the treatment, the serum BDNF levels in both groups increased (all P < 0.01), while no significant difference in serum BDNF level was found between the groups before and after the treatment (all P > 0.05). After the treatment, N400 amplitudes were increased (from 4.73 ± 2.86 μv and 4.51 ± 4.63 μv to 5.35 ± 4.18 μv and 5.52 ± 3.08 μv, respectively) under congruent condition in both risperidone and paliperidone groups (all P < 0.01). Under incongruent conditions, the N400 latencies were shortened in the paliperidone group (from 424.13 ± 110.42 ms to 4.7.41 ± 154.59 ms, P < 0.05), and the N400 amplitudes were increased in the risperidone group (from 5.80 ± 3.50 μv to 7.17 ± 5.51 μv, P < 0.01). After treatment, the total PANSS score in both groups decreased significantly (all P < 0.01), but the difference between the groups was not significant (P > 0.05). A negative correlation between the reduction rate of the PANSS score and the increase in serum BDNF level after the treatment was found in the paliperidone group but not in the risperidone group.

ConclusionsBoth risperidone and paliperidone could increase the serum BDNF levels in patients with first-episode schizophrenia and improve their cognitive function (N400 latency and amplitude), but their antipsychotic mechanisms might differ.

Antipsychotic Agents ; pharmacology ; Brain-Derived Neurotrophic Factor ; drug effects ; China ; Electroencephalography ; Evoked Potentials ; drug effects ; Female ; Humans ; Male ; Paliperidone Palmitate ; pharmacology ; Risperidone ; pharmacology ; Schizophrenia ; drug therapy