An organogenesis network-based comparative transcriptome analysis for understanding early human development in vivo and in vitro

<p>Abstract</p> <p>Background</p> <p>Integrated networks hold great promise in a variety of contexts. In a recent study, we have combined expression and interaction data to identify a putative network underlying early human organogenesis that contains two modules, the stemness-relevant module (hStemModule) and the differentiation-relevant module (hDiffModule). However, owing to its hypothetical nature, it remains unclear whether this network allows for comparative transcriptome analysis to advance our understanding of early human development, both <it>in vivo </it>and <it>in vitro</it>.</p> <p>Results</p> <p>Based on this integrated network, we here report comparisons with the context-dependent transcriptome data from a variety of sources. By viewing the network and its two modules as gene sets and conducting gene set enrichment analysis, we demonstrate the network's utility as a quantitative monitor of the stem potential <it>versus </it>the differentiation potential. During early human organogenesis, the hStemModule reflects the generality of a gradual loss of the stem potential. The hDiffModule indicates the stage-specific differentiation potential and is therefore not suitable for depicting an extended developmental window. Processing of cultured cells of different types further revealed that the hStemModule is a general indicator that distinguishes different cell types in terms of their stem potential. In contrast, the hDiffModule cannot distinguish between differentiated cells of different types but is able to predict differences in the differentiation potential of pluripotent cells of different origins. We also observed a significant positive correlation between each of these two modules and early embryoid bodies (EBs), which are used as <it>in vitro </it>differentiation models. Despite this, the network-oriented comparisons showed considerable differences between the developing embryos and the EBs that were cultured <it>in vitro </it>over time to try to mimic <it>in vivo </it>processes.</p> <p>Conclusions</p> <p>We strongly recommend the use of these two modules either when pluripotent cell types of different origins are involved or when the comparisons made are constrained to the in <it>vivo </it>embryos during early human organogenesis (and an equivalent <it>in vitro </it>differentiation models). Network-based comparative transcriptome analysis will contribute to an increase in knowledge about human embryogenesis, particularly when only transcriptome data are currently available. These advances will add an extra dimension to network applications.</p

Giα proteins exhibit functional differences in the activation of ERK1/2, Akt and mTORC1 by growth factors in normal and breast cancer cells

Background In a classic model, Giα proteins including Gi1α, Gi2α and Gi3α are important for transducing signals from Giα protein-coupled receptors (GiαPCRs) to their downstream cascades in response to hormones and neurotransmitters. Our previous study has suggested that Gi1α, Gi2α and Gi3α are also important for the activation of the PI3K/Akt/mTORC1 pathway by epidermal growth factor (EGF) and its family members. However, a genetic role of these Giα proteins in the activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) by EGF is largely unknown. Further, it is not clear whether these Giα proteins are also engaged in the activation of both the Akt/mTORC1 and ERK1/2 pathways by other growth factor family members. Additionally, a role of these Giα proteins in breast cancer remains to be elucidated. Results We found that Gi1/3 deficient MEFs with the low expression level of Gi2α showed defective ERK1/2 activation by EGFs, IGF-1 and insulin, and Akt and mTORC1 activation by EGFs and FGFs. Gi1/2/3 knockdown breast cancer cells exhibited a similar defect in the activations and a defect in in vitro growth and invasion. The Giα proteins associated with RTKs, Gab1, FRS2 and Shp2 in breast cancer cells and their ablation impaired Gab1’s interactions with Shp2 in response to EGF and IGF-1, or with FRS2 and Grb2 in response to bFGF. Conclusions Giα proteins differentially regulate the activation of Akt, mTORC1 and ERK1/2 by different families of growth factors. Giα proteins are important for breast cancer cell growth and invasion.Fil: Wang, Zhanwei. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Dela Cruz, Rica. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Ji, Fang. Shanghai Jiao Tong University . Sahnghai; ChinaFil: Guo, Sheng. University of Hawaii Cancer Center. Honolulu; Estados Unidos. Shanghai Jiaotong University. Shangha; Estados UnidosFil: Zhang, Jianhua. Shanghai Jiaotong University. Shangha; Estados Unidos. University of Hawaii Cancer Center. Honolulu; Estados UnidosFil: Wang, Ying. David Geffen School of Medicine at UCLA. Los Angeles; Estados UnidosFil: Feng, Gen-Sheng. University of California at San Diego; Estados UnidosFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. National Institutes of Health; Estados UnidosFil: Jiang, Meisheng. David Geffen School of Medicine at UCLA. Los Angeles; Estados UnidosFil: Chu, Wen Ming. University of Hawaii Cancer Center. Honolulu; Estados Unido

Belamcanda chinensis (l.) Dc: Ethnopharmacology, phytochemistryand pharmacology of an important traditional Chinese medicine

Background: Belamcanda chinensis (L.) DC (Iridaceae), a widely used traditional Chinese medicine known as She Gan (Chinese: 射干), is a flowering perennial herb native to East Asia. For thousands of years in China, the rhizome of Belamcanda chinensis has been used to treat inflammation, oxyhepatitis, mumps, acute mastitis, and asthma, as well as throat disorders such as cough, tonsillitis and pharyngitis. Belamcanda chinensis is now listed in the Pharmacopoeia of the People’s Republic of China. The present paper reviews the advancements in the investigation of botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of Belamcanda chinensis.Materials and Methods: Information on Belamcanda chinensis was collected from scientific journals, books, theses and reports via library and electronic search (PubMed, CNKI, Elsevier, ACS, Google Scholar, Baidu Scholar,Web of Science and Science Direct).Results: A number of chemical compounds have been isolated from Belamcanda chinensis, and the major isolated compounds have been identified as isoflavonoids, flavonoids and iridal-type triterpenoids. Among these active compounds, the effects of tectoridin and tectorigenin have been widely investigated. The primary active components in Belamcanda chinensis possess a wide range of pharmacological activities, including anti-inflammatory, anti-oxidative, anti-tumour, anti-alcohol injury, cardiovascular and oestrogenic activities.Conclusions: As an important traditional Chinese medicine, Belamcanda chinensis has been demonstrated to have marked bioactivity, especially in the respiratory system and as an oestrogenic and hepatoprotective agent. This activity is related to its traditional use and provides opportunities for the development of novel drugs and therapeutic products for various diseases. However, the toxicity of Belamcanda chinensis will require further study, and more attention should be devoted to its better utilization.Keywords: Belamcanda chinensis; Ethnopharmacology; Phytochemistry; Pharmacology; Toxicolog

Salvia miltiorrhiza aqueous root extract plays an important role in improving locomotor activity in rats with spinal cord injury

Purpose: To investigate the activity of the aqueous root extract of Salvia miltiorrhiza (S. miltiorrhiza) (Lamiaceae), collected from Anhui Province, China, for the treatment of spinal cord injury (SCI) in Sprague-Dawley (SD) rats.Methods: In total, 30 adult rats were selected and divided into three groups; normal control, untreated and treated. Aqueous root extract of S. miltiorrhiza was introduced intraperitoneally to the treated group. Basso, Beattie and Bresnahan rating scale (BBB) was used to evaluate improvement in locomotor activity after SCI. Total RNA was extracted from tissue sections using Sepasol (NacalaiTesque) and RNA samples were reverse-transcribed using M-MLV reverse transcriptase. BioSense SC-810 Gel Documentation System and Gel-Pro 3.1 software were employed for the analysis of band intensity.Results: A significant reduction in SCI cavity area was observed in the S. miltiorrhiza extract-treated group, relative to the untreated group, after 11 days (0.10 ± 0.05 mm2 treated vs. 0.30 ± 0.01 mm2 untreated). Treatment with root extract also improved the BBB scores; the treated group scored 15, compared to a score of 8 for the untreated group. In addition, the degradation of neurons at the site of injury in the spinal cord was reduced in the treated group compared to the untreated group. Treatment with S. miltiorrhiza aqueous root extract also significantly increased the expression of platelet-derived growth factor-B (PDGF-B) mRNA (p &lt; 0.01).Conclusion: These data suggest that, in addition to other pharmacological activities, S. miltiorrhiza extract has therapeutic potential for the treatment of neuronal degeneration following SCI.Keywords: Salvia Miltiorrhiza, Neurons, Spinal cord injury, Locomotor capacity, Platelet-derived growth factor-B, Basso, Beattie and Bresnahan rating scal

5-(Methoxy­carbon­yl)thio­phene-2-carboxylic acid

In the title compound, C7H6O4S, a monoester derivative of 2,5-thio­phene­dicarboxylic acid, the carboxylic acid and the carboxylic acid ester groups are approximately coplanar with thio­phene ring, making a dihedral angle of 3.1 (4) and 3.6 (4)°, respectively. In the crystal structure, mol­ecules are connected by classical inter­molecular O—H⋯O hydrogen bonds, forming centrosymmetric dimers

Concept-based short text classification and ranking

ABSTRACT Most existing approaches for text classification represent texts as vectors of words, namely &quot;Bag-of-Words.&quot; This text representation results in a very high dimensionality of feature space and frequently suffers from surface mismatching. Short texts make these issues even more serious, due to their shortness and sparsity. In this paper, we propose using &quot;Bag-of-Concepts&quot; in short text representation, aiming to avoid the surface mismatching and handle the synonym and polysemy problem. Based on &quot;Bag-of-Concepts,&quot; a novel framework is proposed for lightweight short text classification applications. By leveraging a large taxonomy knowledgebase, it learns a concept model for each category, and conceptualizes a short text to a set of relevant concepts. A concept-based similarity mechanism is presented to classify the given short text to the most similar category. One advantage of this mechanism is that it facilitates short text ranking after classification, which is needed in many applications, such as query or ad recommendation. We demonstrate the usage of our proposed framework through a real online application: Channel-based Query Recommendation. Experiments show that our framework can map queries to channels with a high degree of precision (avg. precision = 90.3%), which is critical for recommendation applications

MicroRNA-1 acts as a tumor suppressor microRNA by inhibiting angiogenesis-related growth factors in human gastric cancer

Background We recently reported that miR-1 was one of the most significantly downregulated microRNAs in gastric cancer (GC) patients from The Cancer Genome Atlas microRNA sequencing data. Here we aim to elucidate the role of miR-1 in gastric carcinogenesis. Methods We measured miR-1 expression in human GC cell lines and 90 paired primary GC samples, and analyzed the association of its status with clinicopathological features. The effect of miR-1 on GC cells was evaluated by proliferation and migration assay. To identify the target genes of miR-1, bioinformatic analysis and protein array analysis were performed. Moreover, the regulation mechanism of miR-1 with regard to these predicted targets was investigated by quantitative PCR (qPCR), Western blot, ELISA, and endothelial cell tube formation. The putative binding site of miR-1 on target genes was assessed by a reporter assay. Results Expression of miR-1 was obviously decreased in GC cell lines and primary tissues. Patients with low miR-1 expression had significantly shorter overall survival compared with those with high miR-1 expression (P = 0.0027). Overexpression of miR-1 in GC cells inhibited proliferation, migration, and tube formation of endothelial cells by suppressing expression of vascular endothelial growth factor A (VEGF-A) and endothelin 1 (EDN1). Conversely, inhibition of miR-1 with use of antago-miR-1 caused an increase in expression of VEGF-A and EDN1 in nonmalignant GC cells or low-malignancy GC cells. Conclusions MiR-1 acts as a tumor suppressor by inhibiting angiogenesis-related growth factors in human gastric cancer. Downregulated miR-1 not only promotes cellular proliferation and migration of GC cells, but may activates proangiogenesis signaling and stimulates the proliferation and migration of endothelial cells, indicating the possibility of new strategies for GC therapy