Objective To study the inhibitory effect of cyclooxygenase 2 (COX 2) inhibitor celecoxib on the growth of hepatocellular carcinoma cell (HCC) line SMMC 7721 in vitro . Methods Growth suppression was evaluated by MTT method. Apoptosis related changes in morphology were observed by fluorescence microscopy (FM) and transmission electron microscopy (TEM). Apoptotic index (AI) was counted by the TDT mediated dUTP biotin nick end labeling (TUNEL) assay. The apoptotic rate was quantified by flow cytometry (FCM). Results Celecoxib inhibited the growth of HCC cells in a dose dependent manner. The growth inhibitory rates of HCC cells treated with 2, 10, 20, and 40 mmol/L celecoxib were 20.78%, 33.37%, 48 57%, and 64 96%, respectively ( P

Objective To investigate the effect of ischemia and ischemia/reperfusion(I/R)in rat heart on matrix metalloproteinase-1(MMP-1).Methods The I/R animal models were established by shutting down and reopening the anterior interventricular branch with a silver clamp,then the distribution and amount of MMP-1 of the normal and I/R rat hearts were observed by immunohistochemical staining and Western blotting and analyzed by computer image analysis.Results 1.Immunohistochemical staining showed MMP-1 existed mainly in the cardiac matrix.There were strong positive reactions in fibrocytes,smooth muscle cells of the blood vessel and endotheliaI cells of capillaries.MMP-1 didn't show distinct changes 30 minutes after ischemia,while its concentration increased dramatically 60 minutes after ischemia.The positive reaction of MMP-1 increased 30 minutes after I/R,and 60 minutes after I/R there was large fusion areas in MMP-1 existing reglons.2.Quantitative analysis showed no dramatic changes of MMP-1 after ischemia for 30 minutes(P＞0.05),while dramatic changes were seen 60 minutes after ischemia(P＜0.05).MMP-1 changed dramatically 30 minutes and 60 minutes after I/R.3.Western blotting showed that there were no distinct naked-eye-observable changes.The bands of MMP-1 became widened 30 minutes after I/R,and became obviously widened 60 minutes after I/R.Conclusion 1.MMP-1 is secreted by fibrocytes,smooth muscle cells and endothelial cells of cardiac tissue under physiological conditions,and cardiomyocytes has the potential to secrete MMP-1 under ischemia or I/R.2.The longer time the heart ischemia lasts,the greater MMP-1 concentration will increase.Reperfusion can increase MMP-1 concentration to an even higher level,which may be the main cause of the collagen destruction after heart I/R.

Objective: To determine the potency of QN-2013, a derivative of quinoxaline 1,4-N-oxide, as a hypoxia-selective cytotoxin or a radiosensitizer. Methods: In vitro cytotoxicity and radiosensitization, as well as in vivo antitumor activity were determined by colony formation and tumor growth delay respectively. The changes in the cell cycle, DNA damage and repair of damaged DNA were assayed by FCM and “comet” assay, separately. Results: ICN250 and ICair50 of QN-2013 for HeLa-S3 cells were 0.08 and 1.7 mmol*L－1 respectively, namely, HCR=21. This suggested that QN-2013 was a fairly hypoxic cytotoxin, but inferior to SR-4233. QN-2013 had an evident radiosensitization either in vitro or in vivo. It was noted, however, that the value of in vitro SERs increased exponentially with increasing concentration of the drug, but the in situ antitumor activity seemed to be independent of doses of the drug. The systemic toxicity of QN-2013 was superior to an LD50 of 265　mg*kg－1 compared with 80　mg*kg－1 for SR-4233. In hypoxic condition QN-2013 induced S retension effect and G2M block in HeLa-S3 cells, caused DNA double strand break, and inhibited the repair of radiation-induced DNA damages. All of these reactivenesses might be involved in the action mechanism of QN-2013. Conclusion: QN-2013 is a fair hypoxia-selective cytotoxin, and has shown improved antitumor activity in vivo in combination with radiation. In general, These results suggest that the series of quinoxaline di-N-oxide derivatives hold out bright prospect for the development of novel bioreductive antitumor drugs.

As a traditional Chinese medicinal material, Chrysosplenium is urgently needed for genetic resource investigation and protection research due to the decrease of its wild resources in recent years. After investigating the wild resources, we conducted genetic polymorphism and clustering studies of 24 species(a total of 36 samples) of Chrysosplenium using SRAP technique. The results showed that a total of 374 polymorphic bands were obtained using 18 pairs of SRAP primers to amplify these samples, on average of 20.7 bands for each primer pair. We used the biological software to analyze the population's genetic parameter and got the N_a value as 2.000 0, N_(e )value as 1.408 4, the average Nei's index as 0.263 5, and the average Shannon information index as 0.419 1. UPGMA cluster analysis showed that all the samples can be divided into three major groups at the genetic similarity coefficient of 0.70: there are 18 species(24 samples) gathered for the Ⅰ groups, 3 species or variation(7 samples) for Ⅱ groups, and 3 species(5 samples) for Ⅲ groups. The differences of these Chrysosplenium species at the molecular level are consistent with that of their geographical and ecological distribution. At the same time, we used SRAP technology to construct 36 DNA digital fingerprints of Chrysosplenium and obtained the unique molecular identification band type of each material. These results will provide effective methods and reliable basis for the identification, protection and genetic diversity analysis of the germplasm resources of Chrysosplenium, and lay a foundation for the further development and utilization of them.
Cluster Analysis ; DNA Fingerprinting ; Genetic Markers ; Genetic Variation ; Phylogeny ; Polymorphism, Genetic

The aim of this study was to investigate the inhibitory effect and the underlying mechanism of ethacrynic acid (EA) on the contraction in mice. BL-420S force measuring system was used to measure the tension of mouse tracheal rings. The whole cell patch clamp technique was utilized to record the channel currents of airway smooth muscle (ASM) cells. The calcium imaging system was used to determine the intracellular Ca concentration ([Ca]) in ASM cells. The results showed that EA significantly inhibited the high K (80 mmol/L) and acetylcholine (ACh, 100 µmol/L)-induced contraction of mouse tracheal rings in a dose-dependent manner. The maximal relaxation percentages were (97.02 ± 1.56)% and (85.21 ± 0.03)%, and the median effective concentrations were (40.28 ± 2.20) μmol/L and (56.22 ± 7.62) μmol/L, respectively. EA decreased the K and ACh-induced elevation of [Ca] from 0.40 ± 0.04 to 0.16 ± 0.01 and from 0.50 ± 0.01 to 0.39 ± 0.01, respectively. In addition, EA inhibited L-type voltage-dependent calcium channel (LVDCC) and store-operated calcium channel (SOCC) currents in ASM cells, and Ca influx. Moreover, EA decreased the resistance of the respiratory system (Rrs) in vivo in mice. These results indicated that EA inhibits LVDCC and SOCC, which results in termination of Ca influx and decreases of [Ca], leading to relaxation of ASM. Taken together, EA might be a potential bronchodilator.
Animals ; Calcium ; metabolism ; Calcium Channels, L-Type ; Enzyme Inhibitors ; pharmacology ; Ethacrynic Acid ; pharmacology ; Mice ; Muscle Contraction ; drug effects ; Muscle, Smooth ; drug effects ; Respiratory System ; cytology ; drug effects

Objective To investigate the risk factors associated with epididymitis after transurethral resection of prostate.Methods A retrospective analysis of 352 patients with benign prostatic hyperplasia (BPH) who underwent transurethral resection of prostate in X'an Aerospace General Hospital from January 2015 to December 2017 was performed.There were 14 cases of epididymitis and 338 cases of nonepididymitis.Measurement data were expressed as ((x) ± s),t test was used for comparison between groups;count data was expressed by rate (％),and chi-square test was used for comparison between groups.Univariate and multivariate logistic regression analyses were used for factors that may lead to post-urethral epididymitis.Results Univariate logistic regression analysis showed that preoperative leukocytic positive,urine glucose positive and prostate volume had significant effects on postoperative epididymitis (P ＜ 0.05).Multivariate logistic regression analysis showed that prostate volume increased (OR =0.182,P =0.005)was an independent risk factor for postoperative epididymitis.Conclusion The enlargement of prostate volume is an independent risk factor for postoperative epididymitis.For large-volume prostate surgery,the purpose of relieving obstruction can be achieved.

The effect of Tujia medicine Berberidis Radix on endogenous metabolites in the serum and feces of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) was analyzed by metabolomics technology to explore the metabolic pathway and underlying mechanism of Berberidis Radix in the intervention of UC. The UC model was induced in mice by DSS. Body weight, disease activity index(DAI), and colon length were recorded. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in colon tissues were determined by ELISA. The levels of endogenous metabolites in the serum and feces were detected by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites. The potential metabolic pathways were analyzed by MetaboAnalyst 5.0. The results showed that Berberidis Radix could significantly improve the symptoms of UC mice and increase the level of the anti-inflammatory factor IL-10. A total of 56 and 43 differential metabolites were identified in the serum and feces, respectively, belonging to lipids, amino acids, fatty acids, etc. After the intervention by Berberidis Radix, the metabolic disorder gradually recovered. The involved metabolic pathways included biosynthesis of phenylalanine, tyrosine, and tryptophan, linoleic acid metabolism, phenylalanine metabolism, and glycerophospholipid metabolism. Berberidis Radix can alleviate the symptoms of mice with DSS-induced UC, and the mechanism may be closely related to the re-gulation of lipid metabolism, amino acid metabolism, and energy metabolism.
Mice ; Animals ; Colitis, Ulcerative/drug therapy* ; Interleukin-10 ; Metabolomics/methods* ; Chromatography, High Pressure Liquid

ObjectiveTo predict the targets and signaling pathways of Si Junzitang and Tongxie Yaofang in treating ulcerative colitis （UC） following the concept of "same disease with different treatments" based on the network pharmacology and explore the underlying mechanisms. MethodThe differentially expressed genes （DEGs） of UC were extracted from GeoChip. The active components and corresponding potential targets of Si Junzitang and Tongxie Yaofang were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP）. The regulatory networks of Si Junzitang and Tongxie Yaofang were constructed and the protein-protein interaction （PPI） network was plotted. The core genes were predicted， followed by enrichment analysis. The UC model was induced in mice by dextran sodium sulfate （DSS） solution. Mice were randomly divided into a normal group， a UC group， a Si Junzitang group， a Tongxie Yaofang group， and a mesalazine group. Drugs were administered continuously for 14 days. The disease activity index （DAI） was scored for mice in each group. The characteristic values of hemorheology were measured. The serum levels of interleukin-6 （IL-6）， tissue factor （TF）， and hypoxia-inducible factor-1α （HIF-1α） in mice were detected. The relative mRNA expression levels of inhibitory kappa B kinase α （IKKα）， nuclear factor kappa B （NF-κB）， HIF-1α， and vascular endothelial growth factor （VEGF） were measured. ResultA total of 44 genes were obtained by network pharmacological analysis， including 17 common genes. HIF-1 pathway and hypoxia response were potential common targets of Si Junzitang and Tongxie Yaofang in the treatment of UC. The results showed that Si Junzitang and Tongxie Yaofang could significantly reduce DAI score， increase blood perfusion volume and blood cell movement speed， decrease the concentration of mobile red blood cells， reduce the levels of IL-6， TF， and HIF-1α， down-regulate the mRNA expression of IKKα， NF-κB， HIF-1α， and VEGF. ConclusionThe HIF-1 pathway and related targets may be the common targets of Si Junzitang and Tongxie Yaofang to exert different therapeutic effects on the same disease. Si Junzitang is potent in promoting Qi circulation to improve intestinal tissue hypoxia， and Tongxie Yaofang is effective in promoting blood circulation to facilitate intestinal mucosal microcirculation.

Codonopsis Radix is a traditional tonic medicine commonly used in China, which has the effects of strengthening the spleen and tonifying the lung, as well as nourishing blood and engendering liquid. The chemical constituents of Codonopsis species are mainly polyacetylenes, alkaloids, phenylpropanoids, lignans, terpenoids and saponins, flavonoids, steroids, organic acids, saccharides, and so on. Modern pharmacological studies showed that Codonopsis Radix also has a variety of pharmacological effects such as enhancing body immunity, protecting gastrointestinal mucosa and resisting ulcers, promoting hematopoietic function, regulating blood sugar, and delaying aging. In this paper, the chemical constituents of Codonopsis species and the pharmacological effects of Codonopsis Radix were summarized, and on this basis, the quality markers of Codonopsis Radix were analyzed. It was predicted that lobetyolin, tangshenoside I, codonopyrrolidium A, and the oligosaccharides were the possible Q-markers of Codonopsis Radix. This paper will provide scientific references for the quality evaluation and profound research and the development of Codonopsis Radix.
Drugs, Chinese Herbal ; Codonopsis ; Alkaloids ; Medicine, Traditional ; Plant Roots