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Find video protocols related to scientific articles indexed in Pubmed.
Small changes result in large differences: discovery of (-)-incrustoporin derivatives as novel antiviral and antifungal agents.
J. Agric. Food Chem.
PUBLISHED: 08-20-2014
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On the basis of the structure of natural product (-)-incrustoporin (1), a series of lactone compounds 4a-i and 5a-i were designed and synthesized from nitroolefin. The antiviral and antifungal activities of these compounds were evaluated in vitro and in vivo. The small changes between 4 and 5 at the 3,4-position result in large differences in bioactivities. Compounds 4 exhibited significantly higher antiviral activity against tobacco mosaic virus (TMV) than dehydro compounds 5. However, the antifungal activity of 4 is relatively lower than that of 5. Compounds 4a, 4c, and 4i with excellent in vivo anti-TMV activity emerged as new antiviral lead compounds. Compounds 5d-g showed superiority over the commercial fungicides chlorothalonil and carbendazim against Cercospora arachidicola Hor at 50 mg kg(-1). The present study provides fundamental support for the development and optimization of (-)-incrustoporin derivatives as potential inhibitors of plant virus and pathogenic fungi.
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Monitoring changes of tumor microenvironment in colorectal submucosa using multiphoton microscopy.
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PUBLISHED: 07-09-2014
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Recently, targeting tumor microenvironment has become a novel approach for cancer therapy. Collagen is one of important components of tissue microenvironment, and has been considered as a new visible target for cancer therapy. In this work, multiphoton microscopy (MPM) was used to monitor the changes of collagen in tumor microenvironment during tumor progression. It was found that MPM facilitates imaging of tumor cells and collagen. MPM images in different tumor microenvironment during tumor progression shows obvious increase in cell number and collagen degration. In addition, the quantitative analysis of collagen content and orientation index in tumor microenvironment shows significant alteration during tumor progression. These results suggest that MPM has the ability to monitor the changes of collagen morphology in tumor microenvironment and quantify content and orientation index of collagen during tumor progression. Therefore this technique is a powerful imaging tool for the investigation of targeting tumor microenvironment for cancer therapy. SCANNING 9999:XX-XX, 2014. © 2014 Wiley Periodicals, Inc.
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Stereoscopic visualization and quantification of auricular cartilage regeneration in rabbits using multiphoton microscopy.
Scanning
PUBLISHED: 05-13-2014
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Multiphoton microscopy (MPM) was applied for imaging and quantifying the elastic cartilage regeneration tissue in a rabbit ear model without using labeling agents. Morphology of cells and collagen matrix were analysis, showing significant difference between regenerated and intact cartilage in cellular size and collagen distribution. The results demonstrate that high resolution images provide by MPM are consistent with the histological results, and show additional biological behavior which is not visible in standard histology. Advantages in instrumentation may lead to the application of MPM for intravital detection and treatment. SCANNING 36:540-546, 2014. © 2014 Wiley Periodicals, Inc.
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Development of RNA interference-based therapeutics and application of multi-target small interfering RNAs.
Nucleic Acid Ther
PUBLISHED: 05-05-2014
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RNA interference (RNAi) has been proven in recent years to be a newly advanced and powerful tool for development of therapeutic agents toward various unmet medical needs such as cancer, in particular, a great attention has been paid to the development of antineoplastic agents. Recent success in clinical trials related to RNAi-based therapeutics on cancer and ocular disease has validated that small interfering RNAs (siRNAs) constitute a new promising class of therapeutics. Currently, a great wealth of multi-target based siRNA structural modifications is available for promoting siRNA-mediated gene silencing with low side effects. Here, the latest developments in RNAi-based therapeutics and novel structural modifications described for siRNAs--in particular multi-target siRNAs--are reviewed.
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Synthesis and self-assembly of amphiphilic aptamer-functionalized hyperbranched multiarm copolymers for targeted cancer imaging.
Biomacromolecules
PUBLISHED: 04-29-2014
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A novel targeting cancer imaging platform based on aptamer-functionalized amphiphilic hyperbranched copolymer conjugates, which can self-assemble into nanoscopic micelles with a core-shell structure and a narrow size distribution, has been designed and synthesized. The size, morphology, fluorescence performance, and cytotoxicity of micelles were studied by dynamic light scattering, transmission electron microscopy, fluorescence spectroscopy, and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. The results indicate that these micelles have low cytotoxicity against MCF-7 cells and can be easily internalized by MCF-7 cells. In addition, they also exhibit enhanced cell uptake, excellent fluorescence properties, and smart targeting capability in vitro, indicating great potential to be promising carriers for bioimaging and cancer specific delivery.
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Multiphoton microscopy as a diagnostic imaging modality for pancreatic neoplasms without hematoxylin and eosin stains.
J Biomed Opt
PUBLISHED: 04-20-2014
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Hematoxylin and eosin (H&E) staining of tissue samples is the standard approach in histopathology for imaging and diagnosing cancer. Recent reports have shown that multiphoton microscopy (MPM) provides better sample interface with single-cell resolution, which enhances traditional H&E staining and offers a powerful diagnostic tool with potential applications in oncology. The purpose of this study was to further expand the versatility of MPM by establishing the optical parameters required for imaging unstained histological sections of pancreatic neoplasms, thereby providing an efficient and environmentally sustainable alternative to H&E staining while improving the accuracy of pancreatic cancer diagnoses. We found that the high-resolution MPM images clearly distinguish between the structure of normal pancreatic tissues compared with pancreatic neoplasms in unstained histological sections, and discernable differences in tissue architecture and cell morphology between normal versus tumorigenic cells led to enhanced optical diagnosis of cancerous tissue. Moreover, quantitative assessment of the cytomorphological features visualized from MPM images showed significant differences in the nuclear–cytoplasmic ratios of pancreatic neoplasms compared with normal pancreas, as well as further distinguished pancreatic malignant tumors from benign tumors. These results indicate that the MPM could potentially serve as an optical tool for the diagnosis of pancreatic neoplasms in unstained histological sections.
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Identification of dirty necrosis in colorectal carcinoma based on multiphoton microscopy.
J Biomed Opt
PUBLISHED: 02-26-2014
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Dirty necrosis within glandular lumina is often considered as a characteristic of colorectal carcinomas (CRCs) that is a diagnostically useful feature of CRCs with DNA microsatellite instability (MSI). Multiphoton microscopy (MPM), which is based on the second-harmonic generation and two-photon excited fluorescence signals, was used to identify dirty necrosis. Our results demonstrated that MPM has the ability to exhibit the microstructure of dirty necrosis and the signal intensity as well as an emission spectrum that can help to differentiate dirty necrosis from cancer cells. These findings indicate that MPM may be helpful in distinguishing MSI colorectal carcinoma via the identification of dirty necrosis.
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Study on qi deficiency syndrome identification modes of coronary heart disease based on metabolomic biomarkers.
Evid Based Complement Alternat Med
PUBLISHED: 02-11-2014
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Coronary heart disease (CHD) is one of the most important types of heart disease because of its high incidence and mortality. With the era of systems biology bursting into reality, the analysis of the whole biological systems whether they are cells, tissues, organs, or the whole organisms has now become the norm of biological researches. Metabolomics is the branch of science concerned with the quantitative understandings of the metabolite complement of integrated living systems and their dynamic responses to the changes of both endogenous and exogenous factors. The aim of this study is to discuss the characteristics of plasma metabolites in CHD patients and CHD Qi deficiency syndrome patients and explore the composition and concentration changes of the plasma metabolomic biomarkers. The results show that 25 characteristic metabolites related to the CHD patients comparing with the healthy people, and 4 identifiable variables had significant differences between Qi deficiency and non-Qi deficiency patients. On the basis of identifying the different plasma endogenous metabolites between CHD patients and healthy people, we further prompted the metabolic rules, pathogenesis, and biological essence in Qi deficiency syndrome patients.
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Optical diagnosis of gallbladder cancers via two-photon excited fluorescence imaging of unstained histological sections.
Lasers Med Sci
PUBLISHED: 02-09-2014
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Two-photon excited fluorescence (TPEF) microscopy, based on signal from cells, can provide detailed information on tissue architecture and cellular morphology in unstained histological sections to generate subcellular-resolution images from tissue directly. In this paper, we used TPEF microscopy to image microstructure of human normal gallbladder and three types of differentiated carcinomas in order to investigate the morphological changes of tissue structure, cell, cytoplasm, and nucleus without hematoxylin and eosin (H&E) staining. It displayed that TPEF microscopy can well image the stratified normal gallbladder tissue, including the mucosa, the muscularis, and the serosa. The typical cancer cell, characterized by cellular and nuclear pleomorphism, enlarged nuclei, and augmented nucleolus, can be identified in histological sections without H-E staining as well. The quantitative results showed that the areas of the nucleus and the nucleolus in three types of cancerous cells were all significantly greater than those in normal gallbladder columnar epithelial cells derived from TPEF microscopic images. The studies demonstrated that TPEF microscopy has the ability to characterize tissue structures and cell morphology of gallbladder cancers differentiated from a normal gallbladder in a manner similar to traditional histological analysis. As a novel tool, it has the potential for future retrospective studies of tumor staging and migration by utilizing histological section specimens without H-E staining.
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Evaluation of Barrett esophagus by multiphoton microscopy.
Arch. Pathol. Lab. Med.
PUBLISHED: 01-31-2014
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Multiphoton microscopy (MPM) based on 2-photon excitation fluorescence and second-harmonic generation allows simultaneous visualization of cellular details and extracellular matrix components of fresh, unfixed, and unstained tissue. Portable multiphoton microscopes, which could be placed in endoscopy suites, and multiphoton endomicroscopes are in development, but their clinical utility is unknown.
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Effects of traditional Chinese medicine on rats with Type II diabetes induced by high-fat diet and streptozotocin: a urine metabonomic study.
Afr Health Sci
PUBLISHED: 11-20-2013
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Type II diabetes has become a serious threat to human health in recent years. Among adults above 20 years old in China, the prevalence rate of diabetes is 9.7%. Thus, it is imperative to study the mechanisms underlying type II diabetes to develop effective therapeutic treatments.
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Nonequilibrium dynamics of helix reorganization observed by transient 2D IR spectroscopy.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-08-2013
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The relaxation of helical structures very close to equilibrium is observed via transient 2D IR spectroscopy. An initial distribution of synthetically distorted helices having an unnatural bridge linking the 10th and 12th residues of an alanine-rich ?-helix is released to evolve into the equilibrium distribution of ?-helix conformations. The bridge constrains the structure to be slightly displaced from the full ?-helix equilibrium near these residues, yet the peptide is not unfolded completely. The release is accomplished by a subpicosecond pulse of UV irradiation. The resulting 2D IR signals are used to obtain snapshots of the ?100-ps helical conformational reorganization of the distorted dihedral angle and distance between amide units at chemical bond length-scale resolution. The decay rates of the angle between the dipoles, dihedral angles, and distance autocorrelations obtained from molecular dynamics simulations support the experiments, providing evidence that the final helix collapse conforms to linear response theory.
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Metabolomic identification of diagnostic plasma biomarkers in humans with chronic heart failure.
Mol Biosyst
PUBLISHED: 08-20-2013
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Chronic heart failure (CHF), as a progressive clinical syndrome, is characterized by failure of enough blood supply from the heart to meet the bodys metabolic demands, and there is intense interest in identifying novel biomarkers that could make contributions to the diagnosis of CHF. Metabolomics, compared with current diagnostic approaches, could investigate many metabolic perturbations within biological systems. The overarching goal of the work discussed here is to apply a high-throughput approach to identify metabolic signatures and plasma diagnostic biomarkers underlying CHF by 1H-NMR spectroscopy. Plasma samples from 39 patients with CHF and 15 controls were analyzed by NMR spectroscopy. After processing the data, orthogonal partial least square discriminant analysis (OPLS-DA) was performed. The statistical model revealed good explained variance and predictability, and the diagnostic performance assessed by leave-one-out analysis exhibited 92.31% sensitivity and 86.67% specificity. The OPLS-DA score plots of spectra revealed good separation between case and control on the level of metabolites, and multiple biochemical changes indicated hyperlipidemia, alteration of energy metabolism and other potential biological mechanisms underlying CHF. It was concluded that the NMR-based metabolomics approach demonstrated good performance to identify diagnostic plasma markers and provided new insights into metabolic process related to CHF.
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MiR-200a enhances the migrations of A549 and SK-MES-1 cells by regulating the expression of TSPAN1.
J. Biosci.
PUBLISHED: 08-14-2013
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MicroRNA-200a (miR-200a) has been reported to regulate tumour progression in several tumours; however, little is known about its role in non-small cell lung cancer cells (NSCLCs). Here, we found that miR-200a was up-regulated in A549 and SK-MES-1 cells compared with normal lung cells HELF. By a series of gain-of-function and loss-offunction studies, over-expression of miR-200a was indicated to enhance cells migration, and its knock-down inhibited migration of cells in NSCLC cell lines. Furthermore, miR-200a was identified to induce TSPAN1 expression which was related to migration. TSPAN1 was proved to induce migration, and so up-regulation of TSPAN1 by miR-200a may explain why over-expressing miR-200a promotes NSCLC cells migration.
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A New Biomarkers Feature Pattern Consisting of TNF- ? , IL-10, and IL-8 for Blood Stasis Syndrome with Myocardial Ischemia.
Evid Based Complement Alternat Med
PUBLISHED: 07-18-2013
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Objective. To explore new diagnostic patterns for syndromes to overcome the insufficiency of obtainable macrocharacteristics and specific biomarkers. Methods. Chinese miniswines were subjected to Ameroid constrictor, placed around the proximal left anterior descending branch. On the 4th week, macrocharacteristics, coronary angiography, echocardiography, and hemorheology indices were detected for diagnosis. IL-1, IL-6, IL-8, IL-10, TNF- ? , and hsCRP in serum were detected, and Decision Tree was built. Results. According to current official-issued standard, model animals matched the diagnosis of blood stasis syndrome with myocardial ischemia based on findings, including >90% occlusion, attenuated left ventricular segmental motion, dark red or purple tongues, and higher blood viscosity. Significant decrease of IL-10 and increase of TNF- ? were found in model animals. However, in the Decision Tree, besides IL-10 and TNF- ? , IL-8 helped to increase the accuracy of classification to 86%. Conclusions. The Decision Tree building with TNF- ? , IL-10, and IL-8 is helpful for the diagnosis of blood stasis syndrome in myocardial ischemia animals. What is more is that our data set up a new path to the differentiation of syndrome by feature patterns consisting of multiple biomarkers not only for animals but also for patients. We believe that it will contribute to the standardization and international application of syndromes.
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Stromal alterations as quantitative optical biomarkers of epithelial tumor progression.
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PUBLISHED: 07-02-2013
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Stroma plays an important role during epithelial tumor progression. Probing stroma alteration may become an intrinsic indicator for evaluating epithelial tumor progression. In this review, we summarize our recent works on stromal alterations as quantitative optical biomarkers of epithelial tumor progression by use of nonlinear optical microscopy. SCANNING 9999:1-7, 2013. © Wiley Periodicals, Inc.
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Analysis of serum metabolites for the discovery of amino acid biomarkers and the effect of galangin on cerebral ischemia.
Mol Biosyst
PUBLISHED: 06-25-2013
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Ischemic stroke, a devastating disease with a complex pathophysiology, is a leading cause of death and disability worldwide. In our previous study, we reported that galangin provided direct protection against ischemic injury and acted as a potential neuroprotective agent. However, its associated neuroprotective mechanism has not yet been clarified. In this paper, we explored the potential AA biomarkers in the acute phase of cerebral ischemia and the effect of galangin on those potential biomarkers. In our study, 12 AAs were quantified in rat serum and found to be impaired by middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia. Using partial least squares discriminate analysis (PLS-DA), we identified the following amino acids as potential biomarkers of cerebral ischemia: glutamic acid (Glu), homocysteine (Hcy), methionine (Met), tryptophan (Trp), aspartic acid (Asp), alanine (Ala) and tyrosine (Tyr). Moreover, four amino acids (Hcy, Met, Glu and Trp) showed significant change in galangin-treated (100 and 50 mg kg(-1)) groups compared to vehicle groups. Furthermore, we identified three pathway-related enzymes tyrosine aminotransferase (TAT), glutamine synthetase (GLUL) and monocarboxylate transporter (SLC16A10) by multiplex interactions with Glu and Hcy, which have been previously reported to be closely related to cerebral ischemia. Through an analysis of the metabolite-protein network analysis, we identified 16 proteins that were associated with two amino acids by multiple interactions with three enzymes; five of them may become potential biomarkers of galangin for acute ischemic stroke as the result of molecule docking. Our results may help develop novel strategies to explore the mechanism of cerebral ischemia, discover potential targets for drug candidates and elucidate the related regulatory signal network.
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Long double-stranded multiplex siRNAs for dual genes silencing.
Nucleic Acid Ther
PUBLISHED: 05-08-2013
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Simultaneous suppression of multiple oncogenes is an attractive strategy to treat cancers. Herein we present a series of long double-stranded multiplex small interfering RNAs (multi-siRNAs) that is suitable for dual genes silencing through a sequence-specific RNA interference process without inducing significant immune responses. A gap feature structurally designed in either of the nucleotide strands of the multi-siRNAs was proved to be essential toward silencing target genes and avoiding immune responses. Furthermore, the silencing effect of multi-siRNAs against SURVIVIN and BCL-2 genes was shown to be effective and resulted in up-regulation of caspase-3 related apoptosis and, in turn, inhibition of bladder cancer cell proliferation. Our observation suggested that the rationally designed multi-siRNAs would have great potential for therapeutic siRNA design.
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Systems pharmacology strategies for drug discovery and combination with applications to cardiovascular diseases.
J Ethnopharmacol
PUBLISHED: 04-22-2013
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Multi-target therapeutics is a promising paradigm for drug discovery which is expected to produce greater levels of efficacy with fewer adverse effects and toxicity than monotherapies. Medical herbs featuring multi-components and multi-targets may serve as valuable resources for network-based multi-target drug discovery.
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Real-time optical diagnosis for surgical margin in low rectal cancer using multiphoton microscopy.
Surg Endosc
PUBLISHED: 04-15-2013
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Multiphoton microscopy (MPM), based on advances in the field of nonlinear optics and femtosecond lasers, has been shown to provide detailed real-time information on tissue architecture and cell morphology in live tissue. The purpose of this study was to evaluate the feasibility of using MPM to make real-time optical diagnoses for surgical margins in low rectal cancers.
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Wenxin-Keli Regulates the Calcium/Calmodulin-Dependent Protein Kinase II Signal Transduction Pathway and Inhibits Cardiac Arrhythmia in Rats with Myocardial Infarction.
Evid Based Complement Alternat Med
PUBLISHED: 02-21-2013
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Wenxin-Keli (WXKL) is a Chinese herbal compound reported to be of benefit in the treatment of cardiac arrhythmia, cardiac inflammation, and heart failure. Amiodarone is a noncompetitive inhibitor of the ? - and ? -adrenergic receptors and prevents calcium influx in the slow-response cells of the sinoatrial and atrioventricular nodes. Overexpression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias. We hypothesised that administration of WXKL and amiodarone can reduce the incidence of arrhythmias by regulating CaMKII signal transduction. A total of 100 healthy Sprague Dawley rats were used in the study. The rats were randomly divided into four groups (a sham group, a myocardial infarction (MI) group, a WXKL-treated group, and an amiodarone-treated group). A myocardial infarction model was established in these rats by ligating the left anterior descending coronary artery for 4 weeks. Western blotting was used to assess CaMKII, p-CaMKII (Thr-286), PLB, p-PLB (Thr-17), RYR2, and FK binding protein 12.6 (FKBP12.6) levels. The Ca(2+) content in the sarcoplasmic reticulum (SR) and the calcium transient amplitude were studied by confocal imaging using the fluorescent indicator Fura-4. In conclusion, WXKL may inhibit heart failure and cardiac arrhythmias by regulating the CaMKII signal transduction pathway similar to amiodarone.
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Pathway Pattern-based prediction of active drug components and gene targets from H1N1 influenzas treatment with maxingshigan-yinqiaosan formula.
Mol Biosyst
PUBLISHED: 01-25-2013
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Traditional Chinese Medicine (TCM) remedies are composed of different chemical compounds. To understand the underlying pharmacological basis, we need to explore the active components, which function systematically against multiple gene targets to exert efficacy. Predicting active component-gene target interactions could help us decipher the mechanism of action of TCM. Here, we introduce a Pathway Pattern-based method to prioritize the 153 candidate compounds and 7895 associated genes using the extracted Pathway Pattern, which is made up of groups of pathways. The gene prioritization result is compared to previous literature findings to demonstrate the top ranked genes roles in the pathogenesis of H1N1 influenza. Further, molecular docking is utilized to validate compounds effects through docking compounds into drug targets of oseltamivir. After setting thresholds, 16 active components, 29 gene targets and 162 active component-gene target interactions are finally identified to elucidate the pharmacology of maxingshigan-yinqiaosan formula. This novel strategy is expected to serve as a springboard for the efforts to standardize and modernize TCM.
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The effects of xuefu zhuyu and shengmai on the evolution of syndromes and inflammatory markers in patients with unstable angina pectoris after percutaneous coronary intervention: a randomised controlled clinical trial.
Evid Based Complement Alternat Med
PUBLISHED: 01-11-2013
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We evaluated the effects of the Xuefu Zhuyu capsule (XFZY) and the Shengmai capsule (SM) on the evolution of syndromes and inflammatory markers in patients with unstable angina pectoris (UAP) after percutaneous coronary intervention (PCI). Ninety patients with UAP after PCI were randomly and equally assigned to three groups: the XFZY group, the SM group, and the placebo group, with 30 patients in each group. Six syndrome factors (including Qi deficiency, yin deficiency, yang deficiency, blood stasis, phlegm, and Qi stagnation) and 4 inflammatory markers (high-sensitivity C-reactive protein (Hs-CRP), endothelins-1 (ET-1), matrix metalloproteinases-9 (MMP-9), and homocysteine (Hcy)) were observed at week 0 and at the 1st, 4th and 12th weeks. In conclusion, the evolution of syndromes present in patients with UAP after PCI followed these trends (1) The deficiency syndromes gradually increased during a 12-week period, but the excess syndromes first gradually decreased and then mildly increased after PCI. (2) XFZY and SM can prevent excess syndromes from increasing in the later stages and prevent deficiency syndromes from increasing in all stages. (3) XFZY and SMcan reduce the levels of the inflammatory markers, especially in the later stages after PCI.
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A two-level model for the analysis of syndrome of acute ischemic stroke: from diagnostic model to molecular mechanism.
Evid Based Complement Alternat Med
PUBLISHED: 01-10-2013
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Prompt and accurate diagnosis of acute ischemic stroke is critical to seek acute therapy. In traditional Chinese medicine (TCM) science, there is a comprehensive system of diagnosis and medical care of acute ischemic stroke. Here we introduce a two-level model for the analysis of TCM syndrome of acute ischemic stroke. Owing to the limitation of sample size and imbalance, we focused on the analysis of wind-phlegm collateral obstruction syndrome (Feng Tan Yu Zu Zheng). Firstly, a Support-Vector-Machine- (SVM-) based diagnostic model was set up through selection of core symptoms. After pairwise undersampling, we improved the performance of prediction and generated the core symptoms-based diagnostic model of wind-phlegm collateral obstruction syndrome. Next, Pathway Pattern-based method and MetaDrug platform were used to shed light on the molecular basis of the significance of core symptoms in three complementary aspects: symptom-gene-pathway multilayer correlation network, enriched pathways, and most relevant interaction network. The integration of diagnostic model and molecular mechanism analysis creates an interesting perspective for better understanding the syndrome. The two-level model would provide a new opportunity for the study of TCM syndromes.
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Multiphoton Microscopic Imaging of Esophagus During the Early Phase of Tumor Progression.
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PUBLISHED: 01-02-2013
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Esophageal cancer is one of the most common cancer and leading cause of cancer death worldwide. Multiphoton microscopy (MPM) has become a novel optical tool of choice for imaging tissue architecture and cellular morphology based on two-photon excited fluorescence and second harmonic generation. In this study, we used MPM to image microstructure of human normal esophagus, carcinoma in situ, and early invasive carcinoma in order to investigate the morphological change of tissue structure during the early phase of tumor progression. The diagnostic features such as the appearance of cancerous cells, the absence of the basement membrane were extracted to distinguish between normal and cancerous esophagus tissue. The infiltration depth during tumor progression was determined by the appearance of cancerous cells. The significant change of layer structure between cancerous tissue and normal esophagus was described. We also quantitatively described the differences of morphology between normal and cancerous cells. These results correlated well with the corresponding histological findings. With the advancement of clinically miniaturized MPM and the multi-photon probe, combining MPM with standard endoscopy will therefore allow us to make a real-time in vivo diagnosis of early esophageal cancer at the cellular level. SCANNING 9999:1-4, 2013. © Wiley Periodicals, Inc.
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Optical Diagnosis for Lung Cancer Using Multiphoton Imaging.
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PUBLISHED: 01-02-2013
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Currently, hematoxylin-eosin (H-E) stained histopathology is the golden standard for diagnosing lung cancer. This time-consuming procedure needs tissue biopsy, sample fixation, slicing, and labeling. Therefore, the availability of a noninvasive optical diagnosis that can obtain real-time analysis comparable to golden standard H-E stained histopathology will be of extraordinary benefit to the medical community. In this study, we investigated whether multiphoton imaging can make real-time optical diagnosis for normal and cancerous lung tissue, compared with H-E stained histopathology. In the normal lung tissue, we found that multiphoton imaging could display normal lung parenchyma composed of alveolar spaces separated by thin septa. In the cancerous lung tissue, multiphoton imaging clearly illustrated that cancer cells displayed marked cellular and nuclear pleomorphism. These cancer cells were characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio. All of these histopathological features of tissue architecture and cell morphology identified by multiphoton images were readily correlated with H-E staining images. All together, multiphoton imaging can make real-time optical diagnosis for lung cancer. This study provides the groundwork for further using multiphoton imaging to perform real-time noninvasive "optical biopsy" for lung cancer in the near future. SCANNING 9999:XX-XX, 2013. © 2013 Wiley Periodicals, Inc.
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A Review of the Pharmacological Mechanism of Traditional Chinese Medicine in the Intervention of Coronary Heart Disease and Stroke.
Afr J Tradit Complement Altern Med
PUBLISHED: 01-01-2013
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In recent years, several researches have showed that Buyang Huanwu Decoction (BHD) possesses multiple target points in the intervention of diseases, and has same treatment effects on cerebrovascular diseases and cardiovascular diseases. But, there was no full report about the mechanistic and material basis in Brain-Heart concurrent treatment. The objective of the present study was to examine the pharmacological mechanism of traditional Chinese medicine in the intervention of coronary heart disease and stroke. We combined the HIT, PubChem, David Database resource and the networked pharmacology method to ultimately find out BHDs thirty-five potential brain-heart concurrent treatment target points, and preliminarily reveal BHDs material basis for treatment of cerebrovascular diseases and cardiovascular diseases. Finally, the study provided new information with the guidance meanings.
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An effective solution to discover synergistic drugs for anti-cerebral ischemia from traditional chinese medicinal formulae.
PLoS ONE
PUBLISHED: 01-01-2013
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Recently, the pharmaceutical industry has shifted to pursuing combination therapies that comprise more than one active ingredient. Interestingly, combination therapies have been used for more than 2500 years in traditional Chinese medicine (TCM). Understanding optimal proportions and synergistic mechanisms of multi-component drugs are critical for developing novel strategies to combat complex diseases. A new multi-objective optimization algorithm based on least angle regression-partial least squares was proposed to construct the predictive model to evaluate the synergistic effect of the three components of a novel combination drug Yi-qi-jie-du formula (YJ), which came from clinical TCM prescription for the treatment of encephalopathy. Optimal proportion of the three components, ginsenosides (G), berberine (B) and jasminoidin (J) was determined via particle swarm optimum. Furthermore, the combination mechanisms were interpreted using PLS VIP and principal components analysis. The results showed that YJ had optimal proportion 3(G): 2(B): 0.5(J), and it yielded synergy in the treatment of rats impaired by middle cerebral artery occlusion induced focal cerebral ischemia. YJ with optimal proportion had good pharmacological effects on acute ischemic stroke. The mechanisms study demonstrated that the combination of G, B and J could exhibit the strongest synergistic effect. J might play an indispensable role in the formula, especially when combined with B for the acute stage of stroke. All these data in this study suggested that in the treatment of acute ischemic stroke, besides restoring blood supply and protecting easily damaged cells in the area of the ischemic penumbra as early as possible, we should pay more attention to the removal of the toxic metabolites at the same time. Mathematical system modeling may be an essential tool for the analysis of the complex pharmacological effects of multi-component drug. The powerful mathematical analysis method could greatly improve the efficiency in finding new combination drug from TCM.
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Label-free detection of breast masses using multiphoton microscopy.
PLoS ONE
PUBLISHED: 01-01-2013
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Histopathology forms the gold standard for the diagnosis of breast cancer. Multiphoton microscopy (MPM) has been proposed to be a potentially powerful adjunct to current histopathological techniques. A label-free imaging based on two- photon excited fluorescence and second-harmonic generation is developed for differentiating normal breast tissues, benign, as well as breast cancer tissues. Human breast biopsies (including human normal breast tissues, benign as well as breast cancer tissues ) that are first imaged (fresh, unfixed, and unstained) with MPM and are then processed for routine H-E histopathology. Our results suggest that the MPM images, obtained from these unprocessed biopsies, can readily distinguish between benign lesions and breast cancers. In the tissues of breast cancers, MPM showed that the tumor cells displayed marked cellular and nuclear pleomorphism. The tumor cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio, infiltrated into disrupted connective tissue, leading to the loss of second-harmonic generation signals. For breast cancer, MPM diagnosis was 100% correct because the tissues of breast cancers did not have second-harmonic generation signals in MPM imaging. On the contrary, in benign breast masses, second-harmonic generation signals could be seen easily in MPM imaging. These observations indicate that MPM could be an important potential tool to provide label-free noninvasive diagnostic impressions that can guide surgeon in biopsy and patient management.
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Quantitative biomarkers of colonic dysplasia based on intrinsic second-harmonic generation signal.
J Biomed Opt
PUBLISHED: 12-24-2011
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Most colorectal cancers arise from dysplastic lesions, such as adenomatous polyps, and these lesions are difficult to be detected by the current endoscopic screening approaches. Here, we present the use of an intrinsic second-harmonic generation (SHG) signal as a novel means to differentiate between normal and dysplastic human colonic tissues. We find that the SHG signal can quantitatively identify collagen change associated with colonic dysplasia that is indiscernible by conventional pathologic techniques. By comparing normal with dysplastic mucosa, there were significant differences in collagen density and collagen fiber direction, providing substantial potential to become quantitative intrinsic biomarkers for in vivo clinical diagnosis of colonic dysplasia.
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Growth and fabrication of InAs/GaSb type II superlattice mid-wavelength infrared photodetectors.
Nanoscale Res Lett
PUBLISHED: 09-08-2011
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We report our recent work on the growth and fabrication of InAs/GaSb type II superlattice photodiode detectors. The superlattice consists of 9 monolayer InAs/12 monolayer GaSb in each period. Lattice mismatch between the GaSb substrate and the superlattice is 1.5 × 10-4. The full width at half maximum of the first-order satellite peak from X-ray diffraction is 28 arc sec. The P-I-N photodiodes in which the absorption regions (I regions) have 600 periods of superlattice show a 50% cutoff wavelength of 4.3 ?m. The current responsivity was measured at 0.48 A/W from blackbody radiation. The peak detectivity of 1.75 × 1011 cmHz1/2/W and the quantum efficiency of 41% at 3.6 ?m were obtained.PACS: 85.60.-q; 85.60.Gz; 85.35.-Be.
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Discovery of diagnosis pattern of coronary heart disease with qi deficiency syndrome by the T-test-based adaboost algorithm.
Evid Based Complement Alternat Med
PUBLISHED: 08-21-2011
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Coronary heart disease (CHD) is still the leading cause of death for adults worldwide. Traditional Chinese medicine (TCM) has a history of 1000 years fighting against the disease and provides a complementary and alternative treatment to it. Syndrome is the core of TCM diagnosis and it is traditionally diagnosed based on macroscopic symptoms as well as tongue and pulse recognitions of patients. Establishment of the diagnosis method in the microcosmic level is an urgent and major problem in TCM. The aim of this study was to establish characteristic diagnosis pattern for CHD with Qi deficiency syndrome (QDS). Thirty-four biological parameters were detected in 52 patients having unstable angina (UA) with or without QDS. Then, we presented a novel data mining method, t-test-based Adaboost algorithm, to establish highest prediction accuracy with the least number of biological parameters for UA with QDS. We gained a pattern composed of five biological parameters that distinguishes UA with QDS patients from non-QDS patients. The diagnosis accuracy of the patterns could reach 84.5% based on a 3-fold cross validation technique. Moreover, we included 85 UA cases collected from hospitals located in the north and south of China to further verify the association between the pattern and QDS. The classification accuracy is 83.5%, which keeps consistent with the accuracy obtained by the cross-validation technique. The association between a symptom and the five biological parameters was established by the data mining method and it reached an accuracy of ?80%. These results showed that the t-test-based Adaboost algorithm might be a powerful technique for diagnosing syndrome in TCM in the context of CHD.
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Entanglement can completely defeat quantum noise.
Phys. Rev. Lett.
PUBLISHED: 07-29-2011
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We describe two quantum channels that individually cannot send any classical information without some chance of decoding error. But together a single use of each channel can send quantum information perfectly reliably. This proves that the zero-error classical capacity exhibits superactivation, the extreme form of the superadditivity phenomenon in which entangled inputs allow communication over zero-capacity channels. But our result is stronger still, as it even allows zero-error quantum communication when the two channels are combined. Thus our result shows a new remarkable way in which entanglement across two systems can be used to resist noise, in this case perfectly. We also show a new form of superactivation by entanglement shared between sender and receiver.
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Real-time noninvasive optical diagnosis for colorectal cancer using multiphoton microscopy.
Scanning
PUBLISHED: 07-07-2011
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In contrast to colonoscopy biopsy, which contains several disadvantages such as bleeding, sampling error, crush artifact, and time-consuming pathological procedure, multiphoton microscopy (MPM) enables direct noninvasive visualization of tissue architecture and cell morphology in live tissues without the administration of exogenous contrast agents. We performed a proof-of-principle study to evaluate the feasibility of using MPM to make real-time noninvasive optical diagnosis of colorectal cancer by investigating 30 fresh, unfixed, and unstained full-thickness colorectal specimens. We found that MPM images demonstrated irregular tubular structures, reduced stroma, and cellular and nuclear pleomorphism in the cancerous tissues. Cancer cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio, were clearly observed in MPM images, which were comparable to golden standard hematoxylin-eosin staining images. Our findings showed that MPM had the potential to make real-time noninvasive optical diagnosis of colorectal cancer. With miniaturization and integration of colonoscopy, MPM has a promising future in real-time noninvasive "optical biopsy" for colorectal cancer.
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Multiphoton microscopic imaging of in vivo hair mouse skin based on two-photon excited fluorescence and second harmonic generation.
Scanning
PUBLISHED: 06-15-2011
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Mouse is an important animal model to investigate skin physiological and pathological states. In this article, multiphoton microscopic imaging of in vivo hair mouse skin based on two-photon excited fluorescence and second harmonic generation was examined. Our results show that multiphoton microscopy can clearly display microstructure of stratum corneum, stratum spinosum, and dermis of in vivo mouse skin. The main components of epidermis and dermis such as corneocytes, spinosum cell, collagen fibers, and hair follicles can be distinctly identified in MPM images. Using the optional HRZ 200 fine focusing stage, thickness of different layers can be easily assessed. The results demonstrate that MPM can be regarded as an efficient method for in vivo investigation of skin physiological and pathological states by using hair mouse animal model.
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Multiphoton microscopy study of the morphological and quantity changes of collagen and elastic fiber components in keloid disease.
J Biomed Opt
PUBLISHED: 06-07-2011
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Multiphoton microscopy was used to study the extracellular matrix of keloid at the molecular level without tissue fixation and staining. Direct imaging of collagen and elastin was achieved by second harmonic generation and two-photon excited fluorescence, respectively. The morphology and quantity of collagen and elastin in keloid were characterized and quantitatively analyzed in comparison to normal skin. The study demonstrated that in keloid, collagen content increased in both the upper dermis and the deep dermis, while elastin mostly showed up in the deep dermis and its quantity is higher compared to normal skin. This suggests the possibility that abnormal fibroblasts synthesized an excessive amount of collagen and elastin at the beginning of keloid formation, corresponding to the observed deep dermis, while after a certain time point, the abnormal fibroblast produced mostly collagen, corresponding to the observed upper dermis. The morphology of collagen and elastin in keloid was disrupted and presented different variations. In the deep dermis, elastic fibers showed node structure, while collagen showed obviously regular gaps between adjacent bundles. In the upper dermis, collagen bundles aligned in a preferred direction, while elastin showed as sparse irregular granules. This new molecular information provided fresh insight about the development process of keloid.
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Real-time in vivo imaging collagen in lymphedematous skin using multiphoton microscopy.
Scanning
PUBLISHED: 05-02-2011
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Changes of dermal collagen are characteristic for chronic lymphedema. To evaluate these changes, a real-time imaging based on two-photon excited fluorescence and second-harmonic generation was developed for investigating collagen of lymphedematous mouse and rat tail skin in vivo. Our findings showed that the technique could image the morphological changes and distribution of collagen in lymphedematous mouse and rat tail skin in vivo. More importantly, it may allow visualization of dynamic collagen alteration during the progression of lymphedema. Our findings demonstrated that multiphoton microscopy may have potential in a clinical setting as an in vivo diagnostic and monitoring system for therapy in lymphology.
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The relationship between EGFR gain and VHL loss in lung adenocarcinoma and poor patient survival.
Int. J. Clin. Oncol.
PUBLISHED: 04-21-2011
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The prognosis of lung cancer remains poor and clinically applicable prognostic markers have not yet been satisfactory identified. Several chromosomal copy number alterations (CNAs) have been associated with metastasis, relapse, and survival of patients with lung cancer; however, no study has focused exclusively on identifying CNAs at a gene level. The aim of this study was to identify genes whose CNAs are associated with survival of patients with lung adenocarcinoma.
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Identification of key constituents in volatile oil of Ligusticum chuanxiong based on data mining approaches.
Pharm Biol
PUBLISHED: 04-20-2011
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Chinese herbal medicine (CHM) is a complex multicomponent complex system that interacts with multiple targets and functions via multiple pathways based on the whole human system. Therefore, identification of key constituents of Chinese herbals (CH) not only plays a critical role in the quality control of CHM, but also paves a basis for redevelopment of them.
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Establishing diagnostic features for identifying the mucosa and submucosa of normal and cancerous gastric tissues by multiphoton microscopy.
Gastrointest. Endosc.
PUBLISHED: 04-05-2011
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Establishing diagnostic features is essential and significant for developing multiphoton endoscopy to make an early diagnosis of gastric cancer at the cellular level. Until now, these diagnostic features have not been clearly described and understood.
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The effects of allitridi and amiodarone on the conduction system and reverse use-dependence in the isolated hearts of rats with myocardial infarction.
J Ethnopharmacol
PUBLISHED: 03-30-2011
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Allium sativum L. (DaSuan in Mandarin) is a traditional Chinese herb that has been used to prevent and heal cardiovascular diseases.
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Quantification of scar margin in keloid different from atrophic scar by multiphoton microscopic imaging.
Scanning
PUBLISHED: 02-19-2011
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Multiphoton microscopy (MPM) was applied to examine the marginal region at dermis of keloid compared with atrophic scar. High-resolution large-area image showed an obvious boundary at the scar margin and different morphological patterns of elastin and collagen on the two sides, further visualized by the focused three-dimensional images. Content alteration of elastin or collagen between the two sides of boundary was quantified to show significant difference between keloid and atrophic scar. Owing to the raised property of keloid with overproduced collagen on the scar side, the content alteration was positive for elastin and negative for collagen. On the contrary, the content alteration was negative for elastin and positive for collagen in the atrophic scar case due to the atrophic collagen on the scar side. It indicated that examination of the scar margin by MPM may lead a new way to discriminate different types of scars and better understand the scarring mechanisms.
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Label-free discrimination of normal and fibroadenomal breast tissues using second harmonic generation imaging.
Scanning
PUBLISHED: 02-15-2011
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Early detection of fibroadenoma (FA) is critical for preventing subsequent breast cancer. In this work, we show that label-free second harmonic generation (SHG) imaging is feasible and effective in quantitatively differentiating the fibroadenomal tissue from normal breast tissue. With the advent of the clinical portability of miniature SHG microscopy, we believe that the technique has great potential in offering a noninvasive in vivo imaging tool for early detection of FA and monitoring the treatment responses of FA in clinics.
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Association of copy number loss of CDKN2B and PTCH1 with poor overall survival in patients with pulmonary squamous cell carcinoma.
Clin Lung Cancer
PUBLISHED: 02-13-2011
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Although lung cancer is the leading cause of cancer deaths worldwide, reliable markers allowing prediction of patient survival at the time of initial diagnosis are still lacking. Copy number alterations (CNAs) in tumor tissue DNA have been associated with tumorigenesis and malignant progression. We aimed at identification of gene-level CNAs with prognostic value for survival in pulmonary squamous cell carcinoma (SCC).
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Label-free monitoring of colonic cancer progression using multiphoton microscopy.
Biomed Opt Express
PUBLISHED: 02-07-2011
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Real-time histology or virtual biopsy for the diagnosis of colonic cancer is of great medical significance. In this work, we show that label-free multiphoton imaging is feasible and effective in monitoring colonic cancer progression by providing cellular and subcellular details in fresh, unfixed, unstained colonic specimens. Our results also demonstrate the capability of using tissue quantitative analysis of the redox ratio for quantifying colonic cancer progression. These results suggest that multiphoton microscopy has potential to become an in situ histological tool, which is free from the labeling requirement of conventional methods, for the early diagnosis and detection of malignant lesions in the colon.
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Lipid-lowering and antioxidant activities of Jiang-Zhi-Ning in Traditional Chinese Medicine.
J Ethnopharmacol
PUBLISHED: 01-17-2011
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Jiang-Zhi-Ning (JZN) is composed of four Chinese herbs, i.e., Fleeceflower Root, Fructus Crataegi, Folium Nelumbinis and Semen Cassiae. It was used to strengthen blood circulation of coronary artery, arrhythmia and hyperlipidemia.
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Two-photon fluorescence and second-harmonic generation imaging of collagen in human tissue based on multiphoton microscopy.
Scanning
PUBLISHED: 01-06-2011
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Multiphoton microscopic imaging of collagen plays an important role in noninvasive diagnoses of human tissue. In this study, two-photon fluorescence and second-harmonic generation (SHG) imaging of collagen in human skin dermis and submucosa of colon and stomach tissues were investigated based on multiphoton microscopy (MPM). Our results show that multiphoton microscopic image of collagen bundles exhibits apparently different pattern in human tissues. The collagen bundles can simultaneously reveal its SHG and two-photon excited fluorescence images in the submucosa of colon and stomach, whereas it solely emit SHG signal in skin dermis. The intensity spectral information from tissues further demonstrated the above results. This indicates that collagen bundles have completely different space arrangement in these tissues. Our experimental results bring more detailed information of collagen for the application of MPM in human noninvasive imaging.
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Continuous-wave subwavelength microdisk lasers at ? = 1.53 µm.
Opt Express
PUBLISHED: 10-14-2010
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Subwavelength InGaAs/AlInAs microdisk lasers are demonstrated under continuous-wave optical pumping at a heat-sink temperature of 45 K. A 1.49 µm diameter, 209 nm thick microdisk lases in single-mode at a wavelength of 1.53 µm, which is identified as the whispering-gallery mode with the first radial mode number, the fifth azimuthal mode number, and a modal volume of 2.12(?/n)(3) according to our mode simulation.
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[Research on composing principle of anti-phthisis prescriptions based on complex system entropy method].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 09-21-2010
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Using complex system entropy method to analyze composing principle of anti-phthisis prescriptions.
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Characteristics of scar margin dynamic with time based on multiphoton microscopy.
Lasers Med Sci
PUBLISHED: 09-09-2010
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Scar margins dynamic with time were quantitatively characterized using multiphoton microscopy (MPM). 2D large-area and 3D focused images of elastin and collagen at scar margins were obtained to extract quantitative parameters. An obvious boundary was observed at the scar margin, showing altered morphological patterns of elastin and collagen on both sides. Content alteration of elastin and collagen between the two sides of boundary were defined to characterize scar margins from different individuals. The statistical results from 15 normal scar samples strongly demonstrated that content alteration degree of elastin and collagen had decreasing tendency with the increase of patient age or scar duration, consistent with the fact of normal scars regressing spontaneously over time. It indicated that alteration degree can potentially serve as quantitative indicators to examine wound healing and scar progression over time. With the advent of clinical portable multiphoton endoscopes, the MPM technique can be applied in tracking scar formation and progression in vivo by examination of scar margin.
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Oxalate enhanced mechanism of hydroxyl-Fe-pillared bentonite during the degradation of Orange II by UV-Fenton process.
J. Hazard. Mater.
PUBLISHED: 07-17-2010
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An enhanced method of hydroxyl-Fe-pillared bentonite (H-Fe-P-B) during the degradation of Orange II was studied to provide novel insight to interactions of degradation intermediates with heterogeneous catalyst in UV-Fenton system. Based on the degradation mechanism of Orange II, oxalate enhanced mechanism of H-Fe-P-B in heterogeneous UV-Fenton system was developed. The results showed that additional oxalate could increase the Fe leaching of H-Fe-P-B during heterogeneous UV-Fenton process, which led to higher mineralization efficiency of Orange II and lower energy consumption of treatment. When the concentrations of additional sodium oxalate increased up to 0.1 mmol L(-1), 0.2 mmol L(-1) and 0.4 mmol L(-1), the rate of Orange II degradation could increase 30%, 46% and 63%, respectively. The iron ions leached from catalyst could be adsorbed back to the catalyst again after the organic intermediates were mineralized completely. Then the catalyst of H-Fe-P-B could be reused and additional pollution caused by iron ions could be avoided.
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Multiphoton microscopic imaging of normal human rectum tissue.
Scanning
PUBLISHED: 05-13-2010
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In this paper, multiphoton microscopy (MPM), based on two-photon excited fluorescence and second harmonic generation signals, was used to image microstructures of human rectal mucosa and submucosa. The morphology and distribution of the main components in mucosa layer, goblet cells, intestinal glands, and a little collagen fibers have been clearly monitored, and the content and distribution of collagen, elastic fibers, and blood vessels in submucosa layer have also been distinctly obtained. The variation of these components is very relevant to the pathology in gastrointestinal system, especially early rectal cancer. Our results indicate that the MPM technique has the potential application in vivo in the clinical diagnosis and monitoring of early rectal cancer.
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A pilot study of using multiphoton microscopy to diagnose gastric cancer.
Surg Endosc
PUBLISHED: 04-14-2010
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Using a combination of autofluorescence from cells and second-harmonic generation (SHG) signal from collagen, multiphoton microscopy (MPM) imaging can provide detailed real-time information on tissue architecture and cellular morphology in live tissue without administration of exogenous contrast agents. The purpose of this study is to evaluate the feasibility of using MPM to histologically diagnose gastric cancer by using fresh, unfixed, unstained gastric specimens, compared with gold-standard hematoxylin-eosin (H-E)-stained histopathology.
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Monitoring dermal wound healing after mesenchymal stem cell transplantation using nonlinear optical microscopy.
Tissue Eng Part C Methods
PUBLISHED: 01-28-2010
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Nonlinear optical microscopy (NLOM) was applied for monitoring dermal wound healing after mesenchymal stem cell (MSC) transplantation. Our results showed that NLOM can reveal different regeneration processes of collagen in nontreated and MSC-treated wound dermis. Specifically, the temporal increases in the intensity of second-harmonic-generation signals can quantify kinetic properties of collagen regeneration. Orientation analysis of collagen fiber bundles can monitor the formation of new normal collagen fiber bundles, which is an indicator for evaluating the therapy response. It was also found that NLOM can track MSCs location and recruitment. These findings suggested that NLOM is ideal for monitoring the progress of dermal wound healing.
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Stromal optical properties: differentiating normal and cancerous stroma.
Lasers Med Sci
PUBLISHED: 01-18-2010
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This work reports on the measurement of optical properties from nine normal and cancerous human esophageal stroma pairs using reflectance-based confocal microscopy. It was found that the scattering coefficient of cancerous stroma is significantly lower than that of normal stroma. The results suggest that the decreased scattering in cancerous stroma may provide a possible indicator for differentiating normal and cancerous stroma.
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Rational design of cationic lipids for siRNA delivery.
Nat. Biotechnol.
PUBLISHED: 01-17-2010
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We adopted a rational approach to design cationic lipids for use in formulations to deliver small interfering RNA (siRNA). Starting with the ionizable cationic lipid 1,2-dilinoleyloxy-3-dimethylaminopropane (DLinDMA), a key lipid component of stable nucleic acid lipid particles (SNALP) as a benchmark, we used the proposed in vivo mechanism of action of ionizable cationic lipids to guide the design of DLinDMA-based lipids with superior delivery capacity. The best-performing lipid recovered after screening (DLin-KC2-DMA) was formulated and characterized in SNALP and demonstrated to have in vivo activity at siRNA doses as low as 0.01 mg/kg in rodents and 0.1 mg/kg in nonhuman primates. To our knowledge, this represents a substantial improvement over previous reports of in vivo endogenous hepatic gene silencing.
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Transplantation with survivin-engineered mesenchymal stem cells results in better prognosis in a rat model of myocardial infarction.
Eur. J. Heart Fail.
PUBLISHED: 10-31-2009
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To investigate the effect of survivin (SVV)-engineered mesenchymal stem cells (MSCs) on post-infarction cardiac performance and remodelling in rats.
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Multiphoton laser scanning microscopy of localized scleroderma.
Skin Res Technol
PUBLISHED: 10-17-2009
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A real-time, non-invasive method will confer a benefit for the diagnosis and treatment of localized scleroderma (LS) in the clinic. The aim of this work was to demonstrate the potential of multiphoton laser scanning microscopy (MPLSM) for diagnosing LS and monitoring the treatment response in vivo.
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Spectroscopic characterization and microscopic imaging of extracted and in situ cutaneous collagen and elastic tissue components under two-photon excitation.
Skin Res Technol
PUBLISHED: 10-17-2009
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Understanding the two-photon excitation spectral characteristics and microscopic morphology of cutaneous collagen and elastic tissue components is important for applying multiphoton microscopy (MPM) in basic skin biology research and for clinical diagnosis.
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Jadassohn-Pellizzari anetoderma: study of multiphoton microscopy based on two-photon excited fluorescence and second harmonic generation.
Eur J Dermatol
PUBLISHED: 09-09-2009
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Anetoderma is a rare skin disease with loss of dermal elastic tissue resulting in clinically localized areas of flaccid or herniated sack-like skin. In this study, we report a case of Jadassohn-Pellizzari anetoderma, in a 21-year-old Chinese female with an 18-year history of progressively generalized wrinkled skin lesions. Multiphoton microscopy based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) was firstly employed to investigate the pathological process from unaffected skin to the erythematous phase and finally with affected skin of this case. The results showed that the normal elastic fibers in unaffected skin were almost completely absent in erythematous skin tissue, then replaced by a lot of elastic fibers with granular morphology in affected skin, which was consistent with the histopathological results. The obvious changes in collagen fibers and the occurrence of inflammatory cell infiltration in erythematous tissue suggested that the variations of these two components were also the main pathogenesis of anetoderma, except for the deficiency of elastic fibers. Based on these data, we demonstrated that multiphoton microscopy was a promising tool for non-invasive investigation of the pathology of anetoderma at nearly histological resolution, and has potential for observing the dermatological dynamic processes for living specimens because it is based on the intrinsic signals of tissue components.
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Theoretical simulation study of linearly polarized light on microscopic second-harmonic generation in collagen type I.
J Biomed Opt
PUBLISHED: 09-04-2009
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A theoretical model is established for dealing with second-harmonic generation (SHG) in type I collagen excited by linearly polarized light focused by a microscope. With this model, the effects of the polarization angle alpha, numerical aperture (NA), as well as the ratio of hyperpolarizability rho=beta(xxx)beta(xyy) on SHG emission have been investigated. Simulation results reveal that SHG emission power changes periodically as alpha. The use of lower NA leads to weaker SHG emission but is more concentrated in two closer lobes, whereas more distributed emission in two detached lobes appear at higher NA. As the introduction of polarization direction, which is not along with the fiber axis (alpha not equal0 deg), one more element beta(xyy) is valid in our case than beta(xxx) alone, while their ratio rho plays a very important role for collagen features characterization. SHG emission with rho shows complicated modality that SHG emission is different at different alpha and not symmetric at +/-rho except at alpha=0 deg, suggesting the important impact of polarization working on rho for SHG emission. Our theoretical simulation results provide useful clues for experimental study of microscopic SHG emission in collagen excited by linearly polarized beam.
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Two-layered multiphoton microscopic imaging of cervical tissue.
Lasers Med Sci
PUBLISHED: 07-17-2009
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We demonstrate the application of multiphoton microscopy (MPM) based on two-photon excited fluorescence and second harmonic generation signals in imaging two-layered structures of cervical tissue in mice. It was found that MPM is effective for visualizing two-layered cervical microstructures, monitoring the metabolic activity and the density (nuclear-to-cytoplasmic) of epithelial cells, measuring the size of epithelial cell nuclei and the thickness of the epithelial layer, and quantifying collagen in the stroma. These results suggest that, with the advent of clinical portability of typical multiphoton endoscopes, the MPM technique has the potential to be applied in vivo to the clinical diagnosis and monitoring of cervical cancer.
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Extracting diagnostic stromal organization features based on intrinsic two-photon excited fluorescence and second-harmonic generation signals.
J Biomed Opt
PUBLISHED: 05-02-2009
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Intrinsic two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) signals are shown to differentiate between normal and neoplastic human esophageal stroma. It was found that TPEF and SHG signals from normal and neoplastic stroma exhibit different organization features, providing quantitative information about the biomorphology and biochemistry of tissue. By comparing normal with neoplastic stroma, there were significant differences in collagen-related changes, elastin-related changes, and alteration in proportions of matrix molecules, giving insight into the stromal changes associated with cancer progression and providing substantial potential to be applied in vivo to the clinical diagnosis of epithelial precancers and cancers.
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Facile fabrication of well-defined hydrogel beads with magnetic nanocomposite shells.
Int J Pharm
PUBLISHED: 04-21-2009
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Well-defined magnetic nanocomposite beads with alginate gel cores and shells of iron oxide (gamma-Fe(2)O(3)) nanoparticles were prepared by self-assembly of colloidal particles at liquid-liquid interfaces and subsequent in situ gelation. Fe(2)O(3) nanoparticles could spontaneously adsorb onto the water droplet surfaces to stabilize water-in-hexane emulsions. Water droplets containing sodium alginate were in situ gelled by calcium cations, which were released from calcium-ethylenediamine tetraacetic acid (Ca-EDTA) chelate by decreasing pH value through slow hydrolysis of d-glucono-delta-lactone (GDL). The resulting hybrid beads with a core-shell structure were easily collected by removing hexane. This facile and high efficient fabrication had a 100% yield and could be carried out at room temperature. Insulin microcrystal was encapsulated into the hybrid beads by dispersing them in the aqueous solution of alginate sodium in the fabrication process. The sustained release could be obtained due to the dual barriers of the hydrogel core and the close-packed inorganic shell. The release curves were nicely fitted by the Weibull equation and the release followed Fickian diffusion. The hybrid beads may find applications as delivery vehicles for biomolecules, drugs, cosmetics, food supplements and living cells.
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Influence of borate complexation on the electrophoretic behavior of 2-AA derivatized saccharides in capillary electrophoresis.
Carbohydr. Res.
PUBLISHED: 03-14-2009
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A complete separation with baseline resolution of the 2-AA derivatized saccharides, including mono-, di-, and oligosaccharides, was achieved using 50 mM sodium phosphate-150 mM borate solution, pH 7.0 as running buffer by capillary electrophoresis. It was thought to be a result of the inclusion of 150 mM borate in the running electrolyte solution. The formation of borate complexes was observed by means of (11)B and (13)C NMR spectroscopy and the electrophoretic mobilities of the various derivatives were calculated. It was found that steric factors play an important role in the stability of the formed borate complexes, which depends strongly on the configuration of the three vicinal hydroxyl groups at C-2, C-3, and C-4. 2-AA-Glc mainly forms stable 1,2-diester complexes with borate and 2-AA-Mal can form stable 1,2-monoesters. In turn, for 2-AA-Rib the formation of complexes is difficult to take place. The results implied that the configurational difference between the hydroxyl groups could cause the difference in formation of borate complexes leading to significant difference among saccharide molecules in their migration time on CE analysis.
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Label-free imaging characteristics of colonic mucinous adenocarcinoma using multiphoton microscopy.
Scanning
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Colorectal carcinoma (CRC) has high mortality and increased incidence rates. An early detection of CRC is very important. Multiphoton microscopy (MPM) with high resolution and high sensitivity is used to effectively distinguish the microstructure changes of normal and mucinous adenocarcinoma slices of ex vivo human colonic tissues. In mucinous adenocarcinoma mucosa, the glands are distorted and elongated, the gland cavity is indistinct, and the mesh collagen fibers are diminished. In the submucosa, the collagens are seriously disordered, elongated, pushed aside, and sparsely visible, the content of elastic fibers is also broken and almost disappearing. Many cancer cells, some in cavity-like shape full of mucus surrounded by some collagen fibers, occupied the submucosa, which are comparable to hematoxylin-eosin (HE) stained images. Second harmonic generation and two-photon excitation fluorescence (SHG/TPEF) intensity ratio can be used further to quantitatively evaluate normality and abnormality. The fast Fourier transform (FFT) images show that the normal collagen fibrils are dense and in random order, and the cancerous collagen is certainly organized. The exploratory results show that it has potential for the development of multiphoton mini-endoscopy in real-time early diagnosis of CRC.
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Quantitative biomarkers of human skin photoaging based on intrinsic second harmonic generation signal.
Scanning
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Collagen change is a major feature in the photoaged human skin. Here, we present the use of intrinsic second harmonic generation (SHG) signal as a novel means to quantify collagen change with photoaging. We obtain the SHG images of the superficial dermis from ex vivo the cheek skin and the abdomen skin of eight patients aged 55-60 years. The results show that SHG signal can quantitatively reveal collagen change between normal and photoaged human skin in three dimensions. By comparing normal with photoaged dermis, there are significant differences in the collagen content and fine structure, providing substantial potential to be applied in vivo for the clinical diagnosis of human skin photoaging.
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Clinical data mining of phenotypic network in angina pectoris of coronary heart disease.
Evid Based Complement Alternat Med
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Coronary heart disease (CHD) is the leading causes of morbidity and mortality in China. The diagnosis of CHD in Traditional Chinese Medicine (TCM) was mainly based on experience in the past. In this paper, we proposed four MI-based association algorithms to analyze phenotype networks of CHD, and established scale of syndromes to automatically generate the diagnosis of patients based on their phenotypes. We also compared the change of core syndromes that CHD were combined with other diseases, and presented the different phenotype spectra.
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The active ingredients of Jiang-Zhi-Ning: study of the Nelumbo nucifera alkaloids and their main bioactive metabolites.
Molecules
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The object of this study was to identify the major active ingredients of the Chinese Traditional Medicine Jiang-Zhi-Ning (JZN) based on the high performance liquid chromatography (HPLC) profiles of plasma samples obtained from beagle dogs at different times after intragastric administration of JZN, crude JZN extracts, different extracted fractions, different subfractions of the active fraction and different isolated ingredients. 2-Hydroxy-1-methoxyaporphin (2H1M), an alkaloid from Nelumbo nucifera, one of the herbs that make up JZN, was identified as the constituent showing the major pharmacodynamic effect. The major metabolites of 2H1M were analyzed and identified as N-demethyl-2-hydroxy-1-methoxyaporphine-2-O-glycuronic acid, 2-hydroxy-1-methoxy-aporphine-2-O-glycuronic acid and 2-hydroxy-1-methoxy-aporphine-2-O-sulphate. This study provided a comprehensive insight into the active components of JZN.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.