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Objective: To investigate the effects and mechanisms of zinc finger E-box binding homeobox transcription factor-2 ( ZEB2) on the proliferation, colony formation, migration, and invasion abilities and the epithelial-mesenchymal transition (EMT) of PANC-1 cells, a human pancreatic cancer cell line. Methods: Data on the expression of ZEB2 in pancreatic cancer tissues and paracancerous tissues from The Cancer Genome Atlas (TCGA) database were analyzed. PANC-1 pancreatic cancer cells were divided into si-NC group, si- ZEB2 group, pcDNA3.1 group, and pcDNA3.1- ZEB2 group. qRT-PCR and Western blot were conducted to confirm the effectiveness of ZEB2 knockdown or overexpression. CCK-8, colony formation, wound healing, and Transwell assays were conducted to examine the effects of ZEB2 on the proliferation, colony formation, migration, and invasion of PANC-1 cells. qRT-PCR and immunofluorescence assays were performed to examine the expression of E-cadherin and vimentin, the EMT markers, in the cells. Prediction of proteins interacting with ZEB2 was made through the STRING database. Results: TCGA database analysis showed that the expression level of ZEB2 in pancreatic cancer tissues was significantly higher than that in adjacent tissues ( P<0.05). Compared with those of cells in the control group, the proliferation, colony formation, migration, and invasion of cells in the si- ZEB2 group were decreased ( P<0.05). Compared with those of cells in the pcDNA3.1 group, the proliferation, colony formation, migration and invasion of cells in the pcDNA3.1- ZEB2 group were increased (all P<0.05). According to the results of qRT-PCR and immunofluorescence assays, compared with those of the si-NC group, the expression of E-cadherin mRNA, an epithelial marker, in the si- ZEB2 group increased, while the expression of vimentin mRNA, an mesenchymal marker, and the protein decreased. Compared with those of the pcDNA3.1 group, the expression of E-cadherin mRNA in the PANC-1 cells of the pcDNA3.1- ZEB2 group decreased, while the expression of vimentin mRNA and the protein increased (all P<0.05). Analysis with the STRING database predicted that 10 proteins had close interaction with ZEB2. Conclusion: Overexpression of ZEB2 promotes the migration, invasion, and the EMT process of PANC-1 pancreatic cancer cells.
Subject(s)
Apoptosis , Pancreatic Neoplasms , Humans , Vimentin/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Cell Movement , Apoptosis/genetics , Cadherins/genetics , Cadherins/metabolism , Zinc Finger E-box Binding Homeobox 2/genetics , Zinc Finger E-box Binding Homeobox 2/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Transcription Factors/metabolism , Epithelial-Mesenchymal Transition/genetics , RNA, Messenger/genetics , Gene Expression Regulation, Neoplastic , Pancreatic NeoplasmsABSTRACT
BACKGROUND: A comprehensive literature search shows that Sanqi and Huangjing (SQHJ) can improve diabetes treatment in vivo and in vitro, respectively. However, the combined effects of SQHJ on diabetes mellitus (DM) are still unclear. AIM: To explore the potential mechanism of Panax notoginseng (Sanqi in Chinese) and Polygonati Rhizoma (Huangjing in Chinese) for the treatment of DM using network pharmacology. METHODS: The active components of SQHJ and targets were predicted and screened by network pharmacology through oral bioavailability and drug-likeness filtration using the Traditional Chinese Medicine Systems Pharmacology Analysis Platform database. The potential targets for the treatment of DM were identified according to the DisGeNET database. A comparative analysis was performed to investigate the overlapping genes between active component targets and DM treatment-related targets. We constructed networks of the active component-target and target pathways of SQHJ using Cytoscape software and then analyzed the gene functions. Using the STRING database to perform an interaction analysis among overlapping genes and a topological analysis, the interactions between potential targets were identified. Gene Ontology (GO) function analyses and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted in DAVID. RESULTS: We screened 18 active components from 157 SQHJ components, 187 potential targets for active components and 115 overlapping genes for active components and DM. The network pharmacology analysis revealed that quercetin, beta-sitosterol, baicalein, etc. were the major active components. The mechanism underlying the SQHJ intervention effects in DM may involve nine core targets (TP53, AKT1, CASP3, TNF, interleukin-6, PTGS2, MMP9, JUN, and MAPK1). The screening and enrichment analysis revealed that the treatment of DM using SQHJ primarily involved 16 GO enriched terms and 13 related pathways. CONCLUSION: SQHJ treatment for DM targets TP53, AKT1, CASP3, and TNF and participates in pathways in leishmaniasis and cancer.
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BACKGROUND The lncRNA Colorectal Neoplasia Differentially Expressed (CRNDE) gene has been reported as a potential oncogene in NSCLC. Nevertheless, the molecular mechanism of CRNDE in NSCLC progression remains largely unknown. MATERIAL AND METHODS qRT-PCR assay was performed to detect the expression levels of CRNDE, miR-641, and cyclin-dependent kinase 6 (CDK6) in NSCLC. Western blot assay was employed to assess CDK6 protein level in treated NSCLC cells. si-CRNDE#1, si-CRNDE#2, miR-641 mimics, miR-641 inhibitors, or Vector-CDK6 were transfected into NSCLC cells to change the expression levels of CRNDE, miR-641, or CDK6. Dual-luciferase reporter assay was performed to validate the direct interrelated miRNA of CRNDE and the potential target of miR-641. MTT and flow cytometry assays were performed to assess the capacities of cell proliferation and apoptosis, respectively. RESULTS CRNDE level was upregulated in NSCLC, and its knockdown suppressed NSCLC cells proliferation and enhanced apoptosis, whereas miR-641 antagonized the regulatory effect of CRNDE knockdown by directly binding to CRNDE. Moreover, CDK6 was a target of miR-641 and miR-641 exerted anti-proliferation and pro-apoptosis effects through CDK6. CONCLUSIONS CRNDE promoted proliferation and inhibited apoptosis of NSCLC cells at least in part by regulating the miR-641/CDK6 axis, suggesting that CRNDE is a potential therapeutic target for NSCLC treatment.
Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Cyclin-Dependent Kinase 6/metabolism , Lung Neoplasms/metabolism , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Aged , Apoptosis/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cyclin-Dependent Kinase 6/genetics , Disease Progression , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , MicroRNAs/genetics , Middle Aged , Up-RegulationABSTRACT
Three-dimensional (3D) copying of artificial ears and pistol printing are pushing laser three-dimensional copying technique to a new page. Laser three-dimensional scanning is a fresh field in laser application, and plays an irreplaceable part in three-dimensional copying. Its accuracy is the highest among all present copying techniques. Reproducibility degree marks the agreement of copied object with the original object on geometry, being the most important index property in laser three-dimensional copying technique. In the present paper, the error of laser three-dimensional copying was analyzed. The conclusion is that the data processing to the point cloud of laser scanning is the key technique to reduce the error and increase the reproducibility degree. The main innovation of this paper is as follows. On the basis of traditional ant colony optimization, rational ant colony optimization algorithm proposed by the author was applied to the laser three-dimensional copying as a new algorithm, and was put into practice. Compared with customary algorithm, rational ant colony optimization algorithm shows distinct advantages in data processing of laser three-dimensional copying, reducing the error and increasing the reproducibility degree of the copy.
Subject(s)
Algorithms , Computer-Aided Design , Lasers , Printing, Three-Dimensional , Artificial Organs , Ear , Imaging, Three-Dimensional/instrumentation , Phantoms, Imaging , Tissue Engineering/instrumentation , Tissue Engineering/methods , Tissue Engineering/trendsABSTRACT
OBJECTIVE: To evaluate the clinical efficacy of bladder gasification and stasis dispersion combined with antibiotic therapy in the treatment of III A chronic prostatitis. METHODS: We conducted a randomized controlled clinical study on 120 III A prostatitis patients that all met the diagnostic criteria. We divided the patients into groups A, B and C of equal number to receive oral medication of sparfloxacin, sparfloxacin + tamsulosin, and sparfloxacin + herbal decoction, respectively, all for a course of 4 weeks. We evaluated the primary therapeutic indexes according to the total scores of the patients on traditional Chinese medicine (TCM) syndrome and NIH-CPSI and the secondary therapeutic indexes based on the count of white blood cells (WBC) in the expressed prostatic secretion (EPS). RESULTS: After treatment, the total scores on TCM syndrome and NIH-CPSI were significantly reduced in groups B (42.15 +/- 10.29 and 13.25 +/- 6.04) and C (41.26 +/- 11.25 and 12.38 +/- 7.19) than in A (49.43 +/- 11.09 and 17.62 +/- 5.84) ( P < 0.05), and so was the WBC count in EPS in group C (7.76 +/- 15.73) than in groups A (11.45 +/- 10.33) and B (12.28 +/- 13.81) (P < 0.05). The difference between pre- and post-treatment scores on TCM syndrome was more significant in group C (12.65 +/- 11.76) than in B (8.55 +/- 10.15) (P < 0.05). CONCLUSION: Bladder gasification and stasis dispersion combined with antibiotic therapy is effective for the treatment of III A chronic prostatitis, and therefore deserves wide clinical application.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Phytotherapy , Prostatitis/drug therapy , Adult , Chronic Disease , Combined Modality Therapy , Humans , Male , Medicine, Chinese Traditional , Prostatitis/classification , Treatment OutcomeABSTRACT
LEDs are currently used widely to display text, graphics and images in large screens. With red, green and blue LEDs as three primary colors, color rendition will be realized through color mixing. However, LEDs' spectrum will produce drifts with the changes in the temperature environment. With the changes in the driving current simulating changes in the temperature, the three primary color LEDs' spectral drifts were tested, and the drift characteristics of the three primary colors were obtained respectively. Based on the typical characteristics of the LEDs and the differences between LEDs with different colors in composition and molecular structure, the paper analyzed the reason for the spectrum drifts and the drift characteristics of different color LEDs, and proposed the equations of spectrum drifts. Putting the experimental data into the spectrum drift equations, the paper analyzed the impacts of primary colors on the mixed color, pointed out a way to reduce the chromatic aberration, and provided the theory for engineering application of color LEDs.
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Metal-organic frameworks (MOFs) have received great attention due to their fascinating structures and intriguing potential applications in various fields. Herein, we report the first example of the utilization of MOFs for solid-phase microextraction (SPME). MOF-199 with unique pores and open metal sites (Lewis acid sites) was employed as the coating for SPME fiber to extract volatile and harmful benzene homologues. The SPME fiber was fabricated by in situ hydrothermal growth of thin MOF-199 films on etched stainless steel wire. The MOF-199-coated fiber not only offered large enhancement factors from 19,613 (benzene) to 110,860 (p-xylene), but also exhibited wide linearity with 3 orders of magnitude for the tested benzene homologues. The limits of detection for the benzene homologues were 8.3-23.3 ng L(-1). The relative standard deviation (RSD) for six replicate extractions using one SPME fiber ranged from 2.0% to 7.7%. The fiber-to-fiber reproducibility for three parallel prepared fibers was 3.5%-9.4% (RSD). Indoor air samples were analyzed for the benzene homologues using the SPME with the MOF-199-coated fiber in combination with gas chromatography-flame ionization detection. The recoveries for the spiked benzene homologues in the collected indoor air samples were in the range of 87%-106%. The high affinity of the MOF-199-coated fiber to benzene homologues resulted from the combined effects of the large surface area and the unique porous structure of the MOF-199, the pi-pi interactions of the aromatic rings of the analytes with the framework 1,3,5-benzenetricarboxylic acid molecules, and the pi-complexation of the electron-rich analytes to the Lewis acid sites in the pores of MOF-199.
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Identification and characterization of novel genes involved in derangement of metabolisms of glucose and triglycerides are important in understanding the development of metabolic syndrome (MS) and atherosclerosis. Model rats with certain phenotypes of MS were fed a high-carbohydrate diet. The rat hepatic subtracted cDNA libraries were constructed and screened. A novel cDNA of full length was identified by screening of a human hepatic cDNA library with a mixture of probes of the differentially expressed fragments from the rat hepatic subtracted cDNA libraries. The corresponding gene of the cDNA was temporarily named metabolic syndrome-associated gene (MSAG). The predicted protein encoded by MSAG contains 110 amino acids and has a theoretical molecular weight of 11667.04 and an isoelectric point of 4.91. Compared with the housekeeping gene of beta-actin, MSAG had low transcription activity. However, the mRNA level of MSAG in HepG2 cells, a human hepatoma cell line, was significantly increased by glucose and decreased by insulin concentrations higher than physiological levels. These results suggest that MSAG may be involved in the metabolism and/or its regulation of glucose, the functioning of insulin under non-physiological conditions, and further in the development of metabolic syndrome.
Subject(s)
Glucose/pharmacology , Insulin/pharmacology , Proteins/genetics , Amino Acid Sequence , Animals , Cell Cycle Proteins , Cell Line, Tumor , Gene Expression Regulation , Humans , Male , Molecular Sequence Data , Proteins/metabolism , Rats , Rats, Wistar , Sequence Alignment , Sequence Homology, Amino AcidABSTRACT
BACKGROUND: In the general population, selective cyclooxygenase (COX)-2 inhibitors have been associated with fewer gastrointestinal adverse effects (AEs) than NSAIDs, but whether they are associated with exacerbations in patients with inflammatory bowel disease (IBD) remains controversial. OBJECTIVE: The aim of this study was to review published and unpublished findings to determine whether the use of COX-2 inhibitors increased the risk for IBD exacerbations relative to placebo in the treatment of IBD. METHODS: A systematic search of MEDLINE (1966-July 2007), EMBASE (1980-July 2007), the Cochrane Library (2007 Issue 4), US Food and Drug Administration records, and data on file at Novartis Pharmaceuticals Corporation, Pfizer US Pharmaceutical Group, and Merck & Co., Inc., using the search terms celecoxib, rofecoxib, valdecoxib, etoricoxib, lumiracoxib, cyclooxygenase 2 inhibitor, Crohn's disease, ulcerative colitis, and inflammatory bowel disease, was performed to identify randomized, placebo-controlled clinical trials of 5 COX-2 inhibitors in patients with IBD. The publications were fully reviewed for quality. Data on trial design, patient characteristics, intervention drugs, dosages, and outcomes were collected using a predetermined data-extraction form. A meta-analysis was performed based on the publications that met the inclusion/exclusion criteria. RESULTS: Of 588 studies identified in the electronic search, 574 were excluded after screening the titles and abstracts. Fourteen related to the use of COX-2 inhibitors in patients with IBD were reviewed. Two randomized, controlled trials comparing COX-2 inhibitors with placebo were identified. In the first trial, 82 patients were randomized to receive etoricoxib (60-120 mg/d) and 77 to receive placebo. The exacerbation rates were 10.5% (8/76) in the active-treatment group and 11.4% (8/70) in the placebo group (relative risk [RR], 0.92; 95% CI, 0.37-2.32). In the second trial, 112 patients were treated with celecoxib (200 mg BID) and 110 received placebo. The exacerbation rates were 3.7% (4/107) in the celecoxib group and 2.7% (3/110) in the placebo group (RR, 0.73; 95% CI, 0.17-3.18). Of these patients, 5 were lost to follow-up because of AEs. In the meta-analysis comparing COX-2 inhibitors and placebo, the RR was 0.86 (95% CI, 0.39-1.88). No statistically significant differences in IBD relapse rates were found between COX-2 inhibitors and placebo. CONCLUSIONS: The results from this meta-analysis suggest that insufficient data were available to determine the impact of COX-2 inhibitors on IBD exacerbations. The relatively smaller risk for AEs makes the short-term use of COX-2 inhibitors potentially attractive, but the long-term benefits remain unclear. Further studies with sound methodology and large sample sizes are needed to evaluate the tolerability of COX-2 inhibitors in the treatment of IBD.
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OBJECTIVE: To screen prothrombotic state-related cDNA sequences from human hepatic cDNA library. METHODS: The subtracted cDNA library for differentially expressed genes in rat liver of prothrombotic state (PTS) was constructed by suppression subtractive hybridization. Positive clones were identified by differential screening. The target DNA sequences of positive cDNA clones of differentially expressed genes from rat liver of PTS were amplified by PCR. The PCR products were used as probes to screen a human hepatic cDNA library. After the first, second and third screening, the transduction of a positive lambdaTripIEx lysate into E. coli strain BM25. 8 promoted the circularization of pTripIEx. The positive circularized plasmids were identified by double enzyme digestion. The cDNA fragments of the positive plasmids were sequenced and analyzed by bioinformatics (blastn). RESULTS: Four PTS-related cDNA sequences were identified from human hepatic cDNA library. For 3 of them, their products of expression were respectively fibrinogen, LFIRE1, and chromosome 10 open reading frame 104 mRNA. The fourth sequence had homology with carbamoyl-phosphate synthetase 1 gene. CONCLUSION: Four PTS-related cDNA sequences have been identified from human hepatic cDNA library.