Distribution Mechanism of Network Modules in Combined Treatment of Liver Cancer with Jiuwei Zhengxiao Granules / 中国实验方剂学杂志

ObjectiveTo explore the distribution mechanism of network modules in the combined treatment of liver cancer with Jiuwei Zhengxiao granules （JWZX） based on the analysis framework of module pharmacology. MethodThe cell experiment and the animal experiment were carried out to investigate the in vitro anti-liver cancer efficacy of JWZX of different concentrations and the effect on the survival time of H22 ascites tumor mice. By virtue of the analysis strategy of modular pharmacology，the distribution characteristics of nine Chinese drugs in the liver cancer disease network modules were investigated based on the constructed liver cancer disease network and module division by MCODE. In this study，the average degree （AD） of the nodes in the modules was used as an index to screen the main modules of the disease，and the intervention of the sovereign drugs，minister drugs，and assistant drugs on the main modules was explored. Finally，the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed on the drug-acted modules by Metascape. ResultAs revealed by the cell experiment，JWZX could significantly inhibit the proliferation of H22 cells. The animal experiment demonstrated that the medium- and high-dose JWZX could significantly prolong the survival time of mice with H22 ascites tumor （P<0.05，P<0.01）. The distribution of targets of JWZX in the liver cancer disease network modules showed that JWZX interfered with tumor necrosis factor （TNF），epidermal growth factor receptor （EGFR），vascular endothelial growth factor A （VEGFA），transcription factor （JUN），tumor protein p53 （TP53），and other 26 targets and 8 modules. The sovereign drug Ginkgo Semen mainly intervened in modules 3 and 8，and the minister drugs such as Centipeda Herba jointly intervened in modules 1，3，5，8，10，and 12. Centipeda Herba and Phyllanthi Fructus intervened in module 7 and module 19 individually. Artemisiae Annuae Herba and other assistant drugs jointly intervened in modules 3，5，10，and 12. KEGG pathway enrichment analysis found that 135 pathways were enriched in 8 modules，and the pathway functions involved 12 categories including cancer，signal transduction，immune system，endocrine system，and amino acid metabolism. The functions of the four major modules involved cancer，signal transduction，and immune system. According to the results of literature verification，the key links of JWZX on the liver cancer disease network and the core mechanism were presumedly related to the inhibition of phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） and hypoxia-inducible factor-1 （HIF-1） signaling pathways，reduction of the immunosuppressive effect in the tumor microenvironment，and improvement of the anti-tumor immune response. ConclusionJWZX possesses pharmacological activity against liver cancer，and the therapeutic efficacy was achieved through the multiple targets，multiple modules，and multiple functions of drugs alone or in combination to intervene in the disease. The present study reduced the complexity of drug-disease target network analysis with module analysis strategy and explored the network module distribution mechanism of JWZX in the treatment of liver cancer，which provides a new idea for interpreting the complex mechanism of prescription compatibility.

Protective effect and mechanism of Jinshuibao tablet on acute kidney injury induced by cisplatin in rats / 中国药科大学学报

@#This study aimed to observe the therapeutic effect and mechanism of Jinshuibao tablet on acute renal injury induced by cisplatin. Acute renal injury models in SD rats were induced separately by single intraperitoneal injection of cisplatin(5 mg/kg)and intravenous injection for 5 consecutive days at a dosage of 2 mg/kg per day. The renal function and renal histopathological changes were observed in rat acute renal injury models after prevention and treatment with Jinshuibao tablet, respectively. The content of tumor necrosis factor(TNF-α)and reactive oxygen species(ROS), the activity of Caspase 3 and the expression of t-p38, p-p38, Bax and Bcl-2 in the kidneys were detected. The results showed that preventive and therapeutic administration of Jinshuibao tablets could both significantly inhibit the increase of the blood urea nitrogen(BUN)and creatinine(CRE), increase the creatinine clearance rate, reduce the contents of TNF-α and ROS, and decrease the activity of Caspase 3 in acute renal injury models induced by cisplatin. The renal histopathological results showed that Jinshuibao tablets could significantly reduce renal histopathology scores, ameliorate renal tubule degeneration and inflammatory infiltration. Western blot results showed that Jinshuibao tablets could significantly decrease the expression of t-p38 and p-p38, while increasing the Bcl-2/Bax ratio in the kidneys. These results suggested that preventive and therapeutic administration of Jinshuibao tablets could both improve renal function and pathological changes of renal tissue, which might be related to the inhibition of TNF-α and the ROS-p38 MAPK-Caspase3 pathway and thus inhibition of apoptosis.

Inhibitory effect of Xiaochuan pill on obstinate cough and its role in regulation of TLR4MyD88NFκBp65 signaling pathway / 中南大学学报(医学版)

OBJECTIVES@#Cough variant asthma (CVA) is the main cause of obstinate cough. This study aimed to observe the therapeutic effect of Xiaochuan pill on CVA in a rat model, and to explore the mechanisms.@*METHODS@#The rats were sensitized and challenged with 4% ovaibumin (OA) and 2% Al(OH) to establish the CVA models. They were treated with Xiaochuan pill (at the dose of 0.9, 1.8, 3.6 g/kg) or montelukast sodium once a day for 14 days. After 7 and 14 days of intervention, 5 and 10 rats were randomly selected from each group to collect bronchoalveolar lavage fluid (BALF), trachea, and lungs. The number of white blood cells (WBC) and eosinophils (EOS), and the levels of IL-1β, TNF- α, and IFN-γ in BALF were detected. Histopathological examination of lung tissue was performed to observe the histomorphological changes. The expressions of TLR4, MyD88, NF-κBp65, and p-p65 in lung tissue were detected by Western blotting.@*RESULTS@#The numbers of WBC and EOS in BALF of CVA rats were significantly decreased by Xiaochuan pill (<0.05 or <0.01). The hyperplasia of tracheal, bronchial mucosa and the infiltration of inflammatory cells in lung were alleviated obviously. After 14 d of intervention, high dose of Xiaochuan pill significantly increased the level of IFN- γ (<0.01), reduced the levels of IL-1β (<0.05) and TNF-α (<0.05), and decreased the expressions of TLR4, MyD88, p65, and p-p65 (<0.05 or <0.01).@*CONCLUSIONS@#Xiaochuan pill exerts the significant therapeutic effect on obstinate cough in rats. The mechanism of action may be related to the regulation of TLR4-MyD88-NF-κBp65 signaling pathway as well as the inflammation and immune response.

Research progress in adiponectin and cognitive impairment / 中南大学学报(医学版)

Adipocytokines are polypeptides or proteins that are secreted by fat cells with a wide range of biological activities. Adiponectin is a fatty cytokine with insulin sensitization. It possesses the function of anti- diabetes, atherosclerosis and anti-inflammation. Adiponectin may participate in regulating the development of cognitive impairment, which is considered as a new regulatory factor for cognitive impairment.

Research progress on animal models of postpartum depression and their behavior evaluation methods / 中国实验动物学报

Postpartum depression(PPD)is one of the most common types of postpartum psychiatric syndromes. Because of the complex and changeable characteristics in PPD disease and the special period after childbirth, there are many clinical limitations in the study of this disease. Therefore,the preparation and establishment of a proper animal model closed to clinical and behavioral evaluation method plays an important role in study of its pathogenesis. This review mainly introduces the commonly used postpartum depression animal models and the behavioral evaluation method. It is hoped to provide a reference for further study of PPD pathogenesis and for the drug research and development.

Study on the absorption of monosialotetrahexosylganglioside sodium in rats with in situ cycle intestinal perfusion methods / 中国医师杂志

Objective To investigate the duodenum absorptive character of monosialotetrahexosylganglioside sodium (GM1) in rats.Methods The contents of phenolsulfonphthalein (as indicators) and GM1 were determined with ultraviolet-visible (UV) method and high performance liquid chromatography (HPLC) method in rats with in situ cycle intestinal perfusion model.Results The ratio of duodenum absorption of GM1 was 10％ in 2 h after cycle and 22％ in 6 h after cycle,respectively.The Ka was (0.030± 0.012)h,and absorption t1/2 was (25.50 ± 8.56)h in 8 h after cycle.Conclusions GM1 is absorption in rat duodenum,and the accumulate absorption of GM1 is almost linearly related to the cycle time.The absorption dynamics of GM1 may be first-order kinetic process.

Establishment and evaluation of a mouse model of circulating hepatoma cells / 中国实验动物学报

Objective To establish a mouse model of circulating tumor cells (CTCs) by applying mouse hepatoma Hapa 1-6 cells.Methods 108 healthy male C57BL/6 mice were randomly divided into 3 groups according to their body weights.Hepa 1-6 cell suspension was intravenously injected to each mouse in the three groups at a concentration of 1×106,5×106 and 1×107/mL,0.2 mL per mouse,respectively.Blood samples were collected from the mice on the 1st,5th,9th,13th,17th and 21st days after tumor cell injection.The number,ratio and relative inhibition rate of CTCs were calculated in 20,000 nucleated cells.The mortality of mice was recorded.②80 male C57BL/6 mice were averaged into 2 groups according to their body weight: control and sorafenib tosylate groups.0.2 mL of Hepa 1-6 single cell suspension was injected to each mouse through the caudal vein at a concentration of 5×106/mL.The mice were gavaged with sorafenib tosylate (50 mg/kg) for 21 days and blood samples were collected at the 3rd,8th,15th,and 21st days for CTC assessment.Results For the 1×106/mL group,the CTC inhibition rate was 25.1%,18.1%,8.9%,4.4%,2.9% and 0.3% on the 1st,5th,9th,13th,17th and 21st days,respectively,and all the mice were alive.For the 5×106/mL group,the CTC inhibition rate was 40.4%,35.4%,15.4%,9.0%,6.6% and 4.1% on the 1st,5th,9th,13th,17th and 21st days,respectively,and all the mice were alive.For the 1×107/mL group,the CTC inhibition rate was 39.1% and 33.5% on the 1st and 5th days,respectively.Some mice died immediately after intravenous injection and all mice died within 7 days.②The relative clearance of CTCs was-7.5%,4.6%,55.3% and-94.5% on the 3rd,8th,15th and 21st days of sorafenib tosylate administration.Compared with the control group,there were significant differences among the three groups (P<0.05 or P<0.01).Conclusions A mouse model of circulating hepatoma cells has been established by intravenous injection of 0.2 mL of 5×106/mL mouse Hepa 1-6 cell suspension.This mouse model can be used for screening and evaluation of drugs for circulating tumor cell inhibition.

Establishment and assessment of a rat model of functional dyspepsia with spleen deficiency / 中国实验动物学报

Objective To establish animal models of functional dyspepsia with spleen deficiency and to compare the efficacy of different methods.Methods Rat models were established by iodoacetamide(IA)-treatment or combined with swimming.Appearance,body weight,food intake of the rats were observed,and serum motilin,cholecystokinin,lactate,gastrin content and urinary D-xylose excretion rates were detected to confirm whether the model of functional dyspepsia with spleen deficiency was established.Results The IA-treated rats had less food intake and a slower body weight gain.The IA-treated combined with swimming rats presented spleen-hypofunction symptoms,such as emaciation,hair dry and loose stools,their urinary D-xylose excretion rate,serum motilin,gastrin content were decreased,and serum cholecystokinin and lactate contents were increased significantly (P<0.05 for all).Conclusions All the three methods used in this study can result in symptoms of functional dyspepsia with spleen deficiency.However,IA-treatment combined with swimming models appear more close to spleen deficiency-like presentation,and the best model is the IA-treated combined with platform standing.

Delayed cardioprotection of Gingkgo biloba leaf extract and its mechanisms / 中草药

Objective To observe the delayed cardioprotective effect of the extract of Gingkgo biloba leaves(EGb761)and its possible mechanisms in rats.Methods Myocardial ischemia-reperfusion(I/R)injury was induced by 30 min of global ischemia and 30 min of reperfusion in isolated rat hearts.Heart rate(HR),coronary flow(CF),left ventricular pressure(LVP),and its first derivatives(+dp/dtmax)were recorded,and the releasing content of creatine kinase(CK),contents of malondialdehyde(MDA)and nitric oxide(NO)in myocardial tissues were measured.Results Single ig EGb761(50 or 100 mg/kg)at 24 h before I/R were done could significantly attenuate the damage of cardiac function(LVP and +dp/dtmax)and the lowering of NO level in myocardial tissues,and inhibit the increasing in CK release and MDA level induced by I/R in myocardial tissues.The delayed cardioprotective effects of EGb761 were markedly inhibited by pretreatment with L-NAME(5 mg/kg),an inhibitor of NO synthase,or HMR1883(3 mg/kg),an antagonist of sarcolemmal ATP-sensitive potassium channels(sarcKATP).Conclusion Pretreatment with EGb761 could protect against I/R-induced myocardial injury in rats,and the delayed cardioprotection of EGb761 may be related to increasing in NO production and opening of sarcKATP.