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

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

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

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.

BACKGROUND: CpG oligodeoxynucleotide (ODN) is a type of highly effective immune adjuvant with low toxicity, which has an extensive application in gene therapy for many diseases. However, the specificity for species and cells leading to low uptake by cells and degradation by nuclease blocks its clinical application. OBJECTIVE: To explore the specific delivery and its immunologic efficacy of CpG ODN targeting B lymphocytes of umbilical cord blood by CD40 ligand-receptor-mediated carrier system. DESIGN, TIME AND SETTING: An observation and control experiment was performed at the Department of Hematology, and Department of Pediatric, the First Affiliated Hospital of Jinan University from April 2004 to October 2007. MATERIALS: Fresh umbilical cord blood with heparin was obtained from healthy, natal infant. Informed consent was obtained from his parents, and the experiment was approved by the hospital Ethics Committee. METHODS: CD40 ligand (CD40L)-EDC-PLL-CpG ODN conjugated complex was prepared. Mononuclear cells (MNCs) from umbilical cord blood were co-cultured with conjugated complexes. Uptake rate, mean fluorescence intensity of FAM marked CpG ODN, expressions of MNCs, proliferations of lymphocytes and the IgG levels of culture supematants were detected by flow cytometry, fluorescence techniques, MTT assay and ELISA, respectively. MAIN OUTCOME MEASURES: The uptake rate, the mean fluorescence intensity of CpG ODN by MNCs, subgroups and proliferations of lymphocytes, and IgG levels of culture supematants. RESULTS: Compared to the pure CpG ODN group, the uptake rate of the conjugated complexes group was higher (98%), the peak level of up-taking occurred earlier, and intracellular fluorescence intensity maintained much more stable. Expressions of CD19+, CD22+, and CD20+ was increased, A value and IgG levels in supematants were all higher than that of the control group. CONCLUSION: CD40 tigand-receptor-mediated carrier system is helpful for CpG ODN delivery targeting to B lymphocyte, enhancing its immunological efficiency.

Nanoporous ZnO was used as a carrier to prepare drug solid dispersion, the mechanism of which to improve the drug dissolution was also studied. Nanoporous ZnO, obtained through chemical deposition method, was used as a carrier to prepare indomethacin and cilostazol solid dispersions by melt-quenching method, separately. The results of scanning electron microscope, surface area analyzer, fourier transform infra-red spectroscopy, differential scanning calorimeter and X-ray diffraction showed that drugs were implanted into nanopores of ZnO by physical adsorption effect and highly dispersed into nanopores of ZnO in amorphous form, moreover, these nanopores strongly inhibited amorphous recrystallization in the condition of 45 degrees C and 75% RH. In addition, the results of the dissolution tested in vitro exhibited that the accumulated dissolutions of indomethacin and cilostazol solid dispersions achieved about 90% within 5 min and approximately 80% within 30 min. It was indicated in this study that the mechanism of drug dissolution improvement was associated with the effects of nanoporous ZnO carrier on increasing drug dispersion, controlling drug in nanopores as amorphous form and inhibiting amorphous recrystallization.

Objective To explore the imaging features of appendiceal mucinous neoplasms and their correlation with the pathology results.Methods The imaging data of 1 6 patients with histopathology proved appendiceal mucinous neoplasms were analyzed retrospectively including mucinous adenoma in 2,low-grade appendiceal mucinous neoplasm (LAMN)in 10,and appendiceal adenocarcinoma in 4. The imaging features were correlated with the result of pathology.Results Mucinous cystadenoma was usually a long oval or strip low density cystic structures with smooth capsule wall and well defined border.Mucinous adenocarcinoma usually presented as a irregular solid-cystic mass with ill-defined border and nodular or separation enhancement.The tumor often infiltrated adjacent bowels,and some of them were accompanied with pseudomyxoma peritonei (PMP)and abdominal implantation metastasi.LAMN had low potential malignancy.The imaging features were between cystadenoma and cystadenocarcinoma.Most cases were similar to mucinous cystadenoma, and some were like to mucinous cystadenocarcinoma.Conclusion The appendiceal mucinous neoplasms have various imaging manifestations. Some cases show some CT and MRI characteristics,which are benefit to the diagnosis of these diseases.