Humans ; Otorhinolaryngologic Surgical Procedures ; methods ; Quinolones ; therapeutic use ; Respiratory System Agents ; therapeutic use

Animals ; Apigenin ; pharmacology ; Female ; Follicle Stimulating Hormone ; blood ; Gonadotropin-Releasing Hormone ; blood ; Luteinizing Hormone ; blood ; Phytoestrogens ; pharmacology ; Rats

On the basis of web databases, 111 compounds with nephrotoxicity and 90 compounds without nephrotoxicity were collected as data set of nephrotoxicity discrimination model, 39 compounds with tubular necrosis and 39 compounds without tubular necrosis were collected as data set of tubular necrosis discrimination model. The 6 122 molecular descriptors, including physicochemical, charge distribution and geometrical descriptors were calculated to characterize the molecular structure of the above-mentioned compounds. CfsSubsetEval valuation method and BestFirst-D1-N5 searching method were used to select molecular descriptors. Two models with high accuracy were built based on the support vector machine (SVM) approach, respectively. Accuracy, sensitivity, specificity and matthew's correlation coefficient of the two models were all above 70%. By using 22 nephrotoxicity compounds of Chinese medicine, the nephrotoxicity discrimination model was further verified with an accuracy of 72.73%. Using the tubular necrosis discrimination model, 10 potential compounds which can cause tubular necrosis were screened from the positive results of nephrotoxicity discrimination model, 6 of them have been verified by literatures. The results demonstrated that the discrimination models can be applied to screen nephrotoxic compounds from Chinese medicinal materials, and they also offer a new research idea for the further studies on the mechanism of nephrotoxicity.
Drugs, Chinese Herbal ; toxicity ; Nephrons ; drug effects ; Support Vector Machine ; Toxicity Tests ; instrumentation ; methods

In this study, based on web database, 324 neurotoxic compounds and 234 non-neurotoxic compounds were selected as a data set for neurotoxicity discriminative model. 6 122 molecular descriptors, including charge distribution, physicochemical and geometrical descriptors,were calculated to characterize the molecular structure of neurotoxic compounds. The combination of Cfs Subset Evaluation and Best First-D1-N5 searching was used to select molecular descriptors. A discrimination model with high accuracy was built based on the support vector machine (SVM) approach. Meanwhile, the model accuracy, sensitivity and specificity were all above 80%. Besides, 30 traditional Chinese medicine compositions with neurotoxicity were set as external validation to further verify the model accuracy,with anaccuracy of 73.333%. Using the model, 13 potential neurotoxic compounds were screened from Sophorae subprostrate Radix,4 of them were verified by literatures. The results demonstrated that the discrimination model can be applied to screen neurotoxic compounds from Chinese medicinal materials.
Computer Simulation ; Drug Evaluation, Preclinical ; methods ; Medicine, Chinese Traditional ; methods ; Models, Theoretical ; Neurotoxins ; analysis ; chemistry ; Reproducibility of Results ; Support Vector Machine

Nicotinic acid could increase high density lipoprotein and reduce serum total cholesterol, low density lipoprotein cholesterol and triglycerides in human bodies, thus is frequently applied in treating low high-density lipoprotein cholesterol and hypertriglyceridemia in clinic. However, according to the findings, nicotinic acid could also cause adverse effects, such as skin flush, beside its curative effects. In this study, bioisosterism, fragment-based search and Lipinski's Rule of Five were used to preliminarily screen out potential TCM ingredients that may have similar pharmacological effects with nicotinic acid from Traditional Chinese medicine database (TCMD). Afterwards, homology modeling and flexible docking were used to further screen out potential nicotinic acid receptor agonists. As a result, eleven candidate compounds were derived from eight commonly used traditional Chinese medicines. Specifically, all of the candidate compounds' interaction with nicotinic acid receptor was similar to nicotinic acid, and their docking scores were all higher than that of nicotinic acid, but their druggability remained to be further studied. Some of the eight source traditional Chinese medicines were used to lower lipid according to literature studies, implying that they may show effect through above means. In summary, this study provides basis and reference for extracting new nicotinic acid receptor agonists from traditional Chinese medicines and improving the medication status of hyperlipidemia.
Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; chemistry ; Humans ; Models, Molecular ; Molecular Structure ; Nicotinic Acids ; chemistry ; Nicotinic Agonists ; chemistry ; Protein Binding ; Receptors, G-Protein-Coupled ; agonists ; chemistry ; Receptors, Nicotinic ; chemistry

The new revision of Declaration of Helsinki in 2013 has adjusted the structure, added or deleted some provisions on the content and modification, and modificated on the details of some words.Revision of the new version has improved the architecture, perfected the content of the declaration, strengthened the protection of the subjects, increased demand for researchers, and cleared the duty of country, research institutions and bidders.The enlighten-ment to our country are:constantly revised involving human clinical trials of the relevant laws and regulations , to pro-tect rights and interests of the subjects;National obligations for protection of the subjects, clinical trials explore the establishment of national compensation system;Ethics committee responsibilities and clearly positioning, exploring to establish an independent ethical review body.

Objective To investigate the biological effects of Wnt gene in kidney cancer Caki?2 cells. Methods The Wnt gene was silenced in kidney cancer Caki?2 cells by lentivirus vector. The cell proliferate ability of cells in each group were assayed by CCK?8 kit at different time points. The apoptosis of Caki?2 cells was observed after silencing Wnt gene by transmission electron microscope. The invasion ability of each group cells was tested using Transwell chambers. The genes expression changes of Wnt/β?catenin signaling pathway and apoptosis related gene were determined by realtime PCR. Results Compared with the other two groups,the cell proliferate ability of the cells after silencing Wntgene was suppressed,and the difference was statistically significant(P<0.05). Apoptosis increased significantly in shRNA+Caki?2+Wnt group cells with silencing of Wntgene, and apoptotic body appeared in these cells. In invasive experiment,the number of emigrated cells in shRNA+Caki?2+Wnt group were significantly lower than other groups(P<0.05). The expression of Wnt mRNA,β?catenin mRNA and Bcl?2 mRNA in shRNA+Caki?2+Wnt group cells was lower than other groups(P<0.05). Conclusion Silencing of Wnt gene of kidney cancer Caki?2 cells can affect the proliferation rate of the cells, promote the cell apoptosis,and inhibit the invasion ability,which provide certain theoretical basis for the research and development of new drugs and new therapeutic targets.

Acetaminophen ; metabolism ; Animals ; Cells, Cultured ; Drug Interactions ; Flavonoids ; metabolism ; Hepatocytes ; metabolism ; Humans

Traditional Chinese medicine (TCM) has definitely clinical effect in treating hyperlipidemia, but the action mechanism still need to be explored. Based on consulting Chinese Pharmacopoeia (2010), all the lipid-lowering Chinese patent medicines were analyzed by associated rules data mining method to explore high frequency herb pairs. The top three couplet medicines with high support degree were Puerariae Lobatae Radix-Crataegi Fructus, Salviae Miltiorrhizae Radix et Rhizoma-Crataegi Fructus, and Polygoni Multiflori Radix-Crataegi Fructus. The 20 main ingredients were selected from the herb pairs and docked with 3 key hyperlipidemia targets, namely 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), peroxisome proliferator activated receptor-α (PPAR-α ) and niemann-pick C1 like 1 (NPC1L1) to further discuss the molecular mechanism of the high frequency herb pairs, by using the docking program, LibDock. To construct evaluation rules for the ingredients of herb pairs, the root-mean-square deviation (RMSD) value between computed and initial complexes was first calculated to validate the fitness of LibDock models. Then, the key residues were also confirmed by analyzing the interactions of those 3 proteins and corresponding marketed drugs. The docking results showed that hyperin, puerarin, salvianolic acid A and polydatin can interact with two targets, and the other five compounds may be potent for at least one of the three targets. In this study, the multi-target effect of high frequency herb pairs for lipid-lowering was discussed on the molecular level, which can help further researching new multi-target anti-hyperlipidemia drug.
Asteraceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; metabolism ; Humans ; Hydroxymethylglutaryl CoA Reductases ; chemistry ; genetics ; metabolism ; Hyperlipidemias ; drug therapy ; enzymology ; genetics ; metabolism ; Hypolipidemic Agents ; chemistry ; metabolism ; Membrane Proteins ; chemistry ; genetics ; metabolism ; Molecular Docking Simulation ; PPAR alpha ; chemistry ; genetics ; metabolism ; Protein Binding ; Pueraria ; chemistry

Objective To investigate the left ventricular hemodynamic changes of patients with hypertension by echocardiography using vector flow mapping (VFM).Methods Twenty-eight patients with hypertension (hypertension group) and 26 normal subjects (control group) were involved.All the subjects underwent conventional transthoracic echocardiographic examination and VFM on apical 3 chambers view.The evolution of velocity distribution,stream line and vorticity line in left ventricle were observed.Left ventricle was divided into basal,mid and apical segments,in which vorticity parameter (Vmax) were quantitatively measured and analyzed.Its relations to conventional left ventricular parameters (E,A,E/A,EDT,E/e') were then analyzed.Results ①Compared with the control group,LV end-diastolic,end-systolic volumes and E/e' significantly increased.The evolution of velocity distribution,stream line and vorticity in the hypertension group was slightly irregular.② In mid-diastole phase,vorticity of the control group showed the trend (middle＞ base ＞ apex)(P ＜0.05),which wasn't shown in hypertension group.In other phases,vorticity of both groups decreased from base to apex (P ＜0.05).③There were statistically differences in vorticity between the two groups in early diastolic phase,late diastolic phase of apex and late systolic phase of middle (P =0.045,0.004,0.015,respectively).④ There were negative correlations between Vmax in late diastolic phase of every segment and E/A (from basal segment to apex:r =-0.310,-0.334,-0.333;P =0.028,0.020,0.021).There was positive correlation between Vmax in isovolumic contraction time and E/e' (r =0.348,P =0.016).Conclusions VFM can be utilized to analyze left ventricular hemodynamics quantitatively and it may be a good supplement for assessing cardiac diastolic function.