TCMGeneDIT: a database for associated traditional Chinese medicine, gene and disease information using text mining

<p>Abstract</p> <p>Background</p> <p>Traditional Chinese Medicine (TCM), a complementary and alternative medical system in Western countries, has been used to treat various diseases over thousands of years in East Asian countries. In recent years, many herbal medicines were found to exhibit a variety of effects through regulating a wide range of gene expressions or protein activities. As available TCM data continue to accumulate rapidly, an urgent need for exploring these resources systematically is imperative, so as to effectively utilize the large volume of literature.</p> <p>Methods</p> <p>TCM, gene, disease, biological pathway and protein-protein interaction information were collected from public databases. For association discovery, the TCM names, gene names, disease names, TCM ingredients and effects were used to annotate the literature corpus obtained from PubMed. The concept to mine entity associations was based on hypothesis testing and collocation analysis. The annotated corpus was processed with natural language processing tools and rule-based approaches were applied to the sentences for extracting the relations between TCM effecters and effects.</p> <p>Results</p> <p>We developed a database, TCMGeneDIT, to provide association information about TCMs, genes, diseases, TCM effects and TCM ingredients mined from vast amount of biomedical literature. Integrated protein-protein interaction and biological pathways information are also available for exploring the regulations of genes associated with TCM curative effects. In addition, the transitive relationships among genes, TCMs and diseases could be inferred through the shared intermediates. Furthermore, TCMGeneDIT is useful in understanding the possible therapeutic mechanisms of TCMs via gene regulations and deducing synergistic or antagonistic contributions of the prescription components to the overall therapeutic effects. The database is now available at <url>http://tcm.lifescience.ntu.edu.tw/</url>.</p> <p>Conclusion</p> <p>TCMGeneDIT is a unique database that offers diverse association information on TCMs. This database integrates TCMs with biomedical studies that would facilitate clinical research and elucidate the possible therapeutic mechanisms of TCMs and gene regulations.</p

Compartmentalized Culture of Perivascular Stroma and Endothelial Cells in a Microfluidic Model of the Human Endometrium

The endometrium is the inner lining of the uterus. Following specific cyclic hormonal stimulation, endometrial stromal fibroblasts (stroma) and vascular endothelial cells exhibit morphological and biochemical changes to support embryo implantation and regulate vascular function, respectively. Herein, we integrated a resin-based porous membrane in a dual chamber microfluidic device in polydimethylsiloxane that allows long term in vitro co-culture of human endometrial stromal and endothelial cells. This transparent, 2-m porous membrane separates the two chambers, allows for the diffusion of small molecules and enables high resolution bright field and fluorescent imaging. Within our primary human co-culture model of stromal and endothelial cells, we simulated the temporal hormone changes occurring during an idealized 28-day menstrual cycle. We observed the successful differentiation of stroma into functional decidual cells, determined by morphology as well as biochemically as measured by increased production of prolactin. By controlling the microfluidic properties of the device, we additionally found that shear stress forces promoted cytoskeleton alignment and tight junction formation in the endothelial layer. Finally, we demonstrated that the endometrial perivascular stroma model was sustainable for up to 4 weeks, remained sensitive to steroids and is suitable for quantitative biochemical analysis. Future utilization of this device will allow the direct evaluation of paracrine and endocrine crosstalk between these two cell types as well as studies of immunological events associated with normal versus disease-related endometrial microenvironments

Synthesis and Biological Evaluation of Phenanthrenes as Cytotoxic Agents with Pharmacophore Modeling and ChemGPS-NP Prediction as Topo II Inhibitors

In a structure-activity relationship (SAR) study, 3-methoxy-1,4-phenanthrenequinones, calanquinone A (6a), denbinobin (6b), 5-OAc-calanquinone A (7a) and 5-OAc-denbinobin (7b), have significantly promising cytotoxicity against various human cancer cell lines (IC50 0.08–1.66 µg/mL). Moreover, we also established a superior pharmacophore model for cytotoxicity (r = 0.931) containing three hydrogen bond acceptors (HBA1, HBA2 and HBA3) and one hydrophobic feature (HYD) against MCF-7 breast cancer cell line. The pharmacophore model indicates that HBA3 is an essential feature for the oxygen atom of 5-OH in 6a–b and for the carbonyl group of 5-OCOCH3 in 7a–b, important for their cytotoxic properties. The SAR for moderately active 5a–b (5-OCH3), and highly active 6a–b and 7a–b, are also elaborated in a spatial aspect model. Further rational design and synthesis of new cytotoxic phenanthrene analogs can be implemented via this model. Additionally, employing a ChemGPS-NP based model for cytotoxicity mode of action (MOA) provides support for a preliminary classification of compounds 6a–b as topoisomerase II inhibitors

Genetic variation in the tau protein phosphatase-2A pathway is not associated with Alzheimer's disease risk

<p>Abstract</p> <p>Background</p> <p>Tau abnormal hyperphosphorylation and the formation of neurofibrillary tangles in AD brain is the result of upregulation of tau kinases and downregulation of tau phosphatases.</p> <p>Methods</p> <p>In a group of 729 Spanish late-onset Alzheimer's disease (AD) patients and 670 healthy controls, we examined variations into a set of candidate genes (PPP2CA, PPP2R2A, ANP32A, LCMT1, PPME1 and PIN1) in the tau protein phosphatase-2A (PP2A) pathway, to address hypotheses of genetic variation that might influence AD risk.</p> <p>Results</p> <p>There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by age, gender or APOE ε4 allele.</p> <p>Conclusion</p> <p>Our negative findings in the Spanish population argue against the hypothesis that genetic variation in the tau protein phosphatase-2A (PP2A) pathway is causally related to AD risk</p

The Influences of H2Plasma Pretreatment on the Growth of Vertically Aligned Carbon Nanotubes by Microwave Plasma Chemical Vapor Deposition

The effects of H2flow rate during plasma pretreatment on synthesizing the multiwalled carbon nanotubes (MWCNTs) by using the microwave plasma chemical vapor deposition are investigated in this study. A H2and CH4gas mixture with a 9:1 ratio was used as a precursor for the synthesis of MWCNT on Ni-coated TaN/Si(100) substrates. The structure and composition of Ni catalyst nanoparticles were investigated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The present findings showed that denser Ni catalyst nanoparticles and more vertically aligned MWCNTs could be effectively achieved at higher flow rates. From Raman results, we found that the intensity ratio of G and D bands (ID/IG) decreases with an increasing flow rate. In addition, TEM results suggest that H2plasma pretreatment can effectively reduce the amorphous carbon and carbonaceous particles. As a result, the pretreatment plays a crucial role in modifying the obtained MWCNTs structures

Effect of resveratrol on alcohol-induced mortality and liver lesions in mice

BACKGROUND: Resveratrol is a polyphenol with important antiinflammatory and antioxidant properties. We investigated the effect of resveratrol on alcohol-induced mortality and liver lesions in mice. METHODS: Mice were randomly distributed into four groups (control, resveratrol-treated control, alcohol and resveratrol-treated alcohol). Chronic alcohol intoxication was induced by progressively administering alcohol in drinking water up to 40% v/v. The mice administered resveratrol received 10 mg/ml in drinking water. The animals had free access to standard diet. Blood levels were determined for transaminases, IL-1 and TNF-α. A histological evaluation was made of liver damage, and survival among the animals was recorded. RESULTS: Transaminase concentration was significantly higher in the alcohol group than in the rest of the groups (p < 0.05). IL-1 levels were significantly reduced in the alcohol plus resveratrol group compared with the alcohol group (p < 0.05). TNF-α was not detected in any group. Histologically, the liver lesions were more severe in the alcohol group, though no significant differences between groups were observed. Mortality in the alcohol group was 78% in the seventh week, versus 22% in the alcohol plus resveratrol group (p < 0.001). All mice in the alcohol group died before the ninth week. CONCLUSION: The results obtained suggest that resveratrol reduces mortality and liver damage in mice

Widespread exon skipping triggers degradation by nuclear RNA surveillance in fission yeast.

Exon skipping is considered a principal mechanism by which eukaryotic cells expand their transcriptome and proteome repertoires, creating different splice variants with distinct cellular functions. Here we analyze RNA-seq data from 116 transcriptomes in fission yeast (Schizosaccharomyces pombe), covering multiple physiological conditions as well as transcriptional and RNA processing mutants. We applied brute-force algorithms to detect all possible exon-skipping events, which were widespread but rare compared to normal splicing events. Exon-skipping events increased in cells deficient for the nuclear exosome or the 5'-3' exonuclease Dhp1, and also at late stages of meiotic differentiation when nuclear-exosome transcripts decreased. The pervasive exon-skipping transcripts were stochastic, did not increase in specific physiological conditions, and were mostly present at less than one copy per cell, even in the absence of nuclear RNA surveillance and during late meiosis. These exon-skipping transcripts are therefore unlikely to be functional and may reflect splicing errors that are actively removed by nuclear RNA surveillance. The average splicing rate by exon skipping was ∼ 0.24% in wild type and ∼ 1.75% in nuclear exonuclease mutants. We also detected approximately 250 circular RNAs derived from single or multiple exons. These circular RNAs were rare and stochastic, although a few became stabilized during quiescence and in splicing mutants. Using an exhaustive search algorithm, we also uncovered thousands of previously unknown splice sites, indicating pervasive splicing; yet most of these splicing variants were cryptic and increased in nuclear degradation mutants. This study highlights widespread but low frequency alternative or aberrant splicing events that are targeted by nuclear RNA surveillance

Multifunctional biophotonic nanostructures inspired by the longtail glasswing butterfly for medical devices

Numerous living organisms possess biophotonic nanostructures that provide colouration and other diverse functions for survival. While such structures have been actively studied and replicated in the laboratory, it remains unclear whether they can be used for biomedical applications. Here, we show a transparent photonic nanostructure inspired by the longtail glasswing butterfly (Chorinea faunus) and demonstrate its use in intraocular pressure (IOP) sensors in vivo. We exploit the phase separation between two immiscible polymers (poly(methyl methacrylate) and polystyrene) to form nanostructured features on top of a Si3_N_4 substrate. The membrane thus formed shows good angle-independent white-light transmission, strong hydrophilicity and anti-biofouling properties, which prevent adhesion of proteins, bacteria and eukaryotic cells. We then developed a microscale implantable IOP sensor using our photonic membrane as an optomechanical sensing element. Finally, we performed in vivo testing on New Zealand white rabbits, which showed that our device reduces the mean IOP measurement variation compared with conventional rebound tonometry without signs of inflammation

Deterministic diffusion fiber tracking improved by quantitative anisotropy

Diffusion MRI tractography has emerged as a useful and popular tool for mapping connections between brain regions. In this study, we examined the performance of quantitative anisotropy (QA) in facilitating deterministic fiber tracking. Two phantom studies were conducted. The first phantom study examined the susceptibility of fractional anisotropy (FA), generalized factional anisotropy (GFA), and QA to various partial volume effects. The second phantom study examined the spatial resolution of the FA-aided, GFA-aided, and QA-aided tractographies. An in vivo study was conducted to track the arcuate fasciculus, and two neurosurgeons blind to the acquisition and analysis settings were invited to identify false tracks. The performance of QA in assisting fiber tracking was compared with FA, GFA, and anatomical information from T 1-weighted images. Our first phantom study showed that QA is less sensitive to the partial volume effects of crossing fibers and free water, suggesting that it is a robust index. The second phantom study showed that the QA-aided tractography has better resolution than the FA-aided and GFA-aided tractography. Our in vivo study further showed that the QA-aided tractography outperforms the FA-aided, GFA-aided, and anatomy-aided tractographies. In the shell scheme (HARDI), the FA-aided, GFA-aided, and anatomy-aided tractographies have 30.7%, 32.6%, and 24.45% of the false tracks, respectively, while the QA-aided tractography has 16.2%. In the grid scheme (DSI), the FA-aided, GFA-aided, and anatomy-aided tractographies have 12.3%, 9.0%, and 10.93% of the false tracks, respectively, while the QA-aided tractography has 4.43%. The QA-aided deterministic fiber tracking may assist fiber tracking studies and facilitate the advancement of human connectomics. © 2013 Yeh et al