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Docetaxel (DTX) is an effective and commonly used chemotherapeutic drug for cancer. However, its efficacy is greatly compromised because of its toxicity and poor water solubility. In order to overcome these disadvantages, three inclusion complexes between DTX and alkylenediamine-modified β-cyclodextrins (H1-3) with ethylene, propylene and butylene segments were prepared and characterized. The phase solubility studies demonstrated that the stoichiometry of the inclusion complexes between H1-3 and DTX were 1 : 1. The binding abilities of host H1-3 towards DTX decrease in the following order: H3 > H2 > H1, which had good consistency with the decreasing alkylene lengths of these hosts. The water solubility of DTX is remarkably increased 216, 242 and 253 times after forming inclusion complexes with H1-3, respectively. In vitro release studies of DTX from H1-3/DTX into NaAc-HAc buffer solution (pH 5.0) or PBS (pH 7.4) exhibited a preliminary stage burst effect and followed by a slow drug release. The cytotoxicity studies revealed that the H1-3/DTX inclusion complexes exhibited better cytotoxicity profiles against MCF-7, SW480 and A-549 cells than that of DTX. Furthermore, compared with the treatment of DTX, the H1/DTX inclusion complex significantly increased the cell apoptosis percentage from 17.2% to 30.2% (5 μg mL -1 ), 19.0% to 31.0% (10 μg mL -1 ), and 19.3% to 32.2% (15 μg mL -1 ), respectively. These results will provide useful information for H1-3/DTX inclusion complexes as safe and efficient anticancer drug formulations., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We present a novel approach to identify human microRNA (miRNA) regulatory modules (mRNA targets and relevant cell conditions) by biclustering a large collection of mRNA fold-change data for sequence-specific targets. Bicluster targets were assessed using validated messenger RNA (mRNA) targets and exhibited on an average 17.0% (median 19.4%) improved gain in certainty (sensitivity + specificity). The net gain was further increased up to 32.0% (median 33.4%) by incorporating functional networks of targets. We analyzed cancer-specific biclusters and found that the PI3K/Akt signaling pathway is strongly enriched with targets of a few miRNAs in breast cancer and diffuse large B-cell lymphoma. Indeed, five independent prognostic miRNAs were identified, and repression of bicluster targets and pathway activity by miR-29 was experimentally validated. In total, 29 898 biclusters for 459 human miRNAs were collected in the BiMIR database where biclusters are searchable for miRNAs, tissues, diseases, keywords and target genes., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Gene-set analysis (GSA) has been commonly used to identify significantly altered pathways or functions from omics data. However, GSA often yields a long list of gene-sets, necessitating efficient post-processing for improved interpretation. Existing methods cluster the gene-sets based on the extent of their overlap to summarize the GSA results without considering interactions between gene-sets., Results: Here, we presented a novel network-weighted gene-set clustering that incorporates both the gene-set overlap and protein-protein interaction (PPI) networks. Three examples were demonstrated for microarray gene expression, GWAS summary, and RNA-sequencing data to which different GSA methods were applied. These examples as well as a global analysis show that the proposed method increases PPI densities and functional relevance of the resulting clusters. Additionally, distinct properties of gene-set distance measures were compared. The methods are implemented as an R/Shiny package GScluster that provides gene-set clustering and diverse functions for visualization of gene-sets and PPI networks., Conclusions: Network-weighted gene-set clustering provides functionally more relevant gene-set clusters and related network analysis.

Rab23 has been proven to play a role in membrane trafficking and protein transport in eukaryotic cells. Rab23 is also a negative regulator of the Sonic hedgehog (Shh) signaling pathway in an indirect way. The nonsense mutation and loss of protein of Rab23 has been associated with neural tube defect in mice and aberrant expression in various diseases in human such as neural system, breast, visceral, and cutaneous tumor. In addition, Rab23 may play joint roles in autophagosome formation during anti-infection process against Group A streptococcus. In this review, we give a brief review on the functions of Rab23, summarize the involvement of Rab23 in genetic research, membrane trafficking, and potential autophagy pathway, especially focus on tumor promotion, disease pathogenesis, and discuss the possible underlying mechanisms that are regulated by Rab23., (© 2017 The Author(s).)

The title compound, C 17 H 13 Br 2 N 3 O·C 4 H 5 NO 2 , is a co-crystal of N -(7-di-bromo-methyl-5-methyl-1,8-naphthyridin-2-yl)benzamide and pyrrolidine-2,5-dione (succinimide). The benzamide mol-ecule exhibits pseudo-mirror symmetry, with an r.m.s. deviation of the non-H atoms of 0.09 Å (except for the two Br atoms). The angle between the least-squares planes of the two mol-ecules is 26.2 (2)°. In the crystal, the two mol-ecules are mutually linked by N-H⋯O and N-H⋯N hydrogen bonds. The packing is consolidated by C-H⋯(O,N) hydrogen bonds and π-π stacking inter-actions.

The mol-ecule of the title 1,8-naphthyridine-BF 2 derivative, C 12 H 10 BBr 2 F 2 N 3 O, is located on a mirror plane running parallel to the entire ring system and the attached methyl C atoms. Individual mol-ecules are stacked along the b- axis direction. The cohesion in the crystal structure is accomplished by C-H⋯F hydrogen bonds and additional off-set π-π inter-actions [centroid-to-centroid distance = 3.6392 (9) Å, slippage 0.472 Å], leading to the formation of a three-dimensional supra-molecular network.

In the title compound, C9H9NO3·H2O, the plane of the acetamide group is oriented at 20.52 (8)° with respect to the benzene ring, whereas the plane of the carb-oxy-lic acid group is essentially coplanar with the benzene ring [maximum deviation = 0.033 (1) Å]. In the crystal, classical O-H⋯O and N-H⋯O hydrogen bonds and weak C-H⋯O hydrogen bonds link the organic mol-ecules and water mol-ecules of crystallization into a three-dimensional supra-molecular architecture.

Background: Genome-wide expression profiles reflect the transcriptional networks specific to the given cell context. However, most statistical models try to estimate the average connectivity of the networks from a collection of gene expression data, and are unable to characterize the context-specific transcriptional regulations. We propose an approach for mining context-specific transcription networks from a large collection of gene expression fold-change profiles and composite gene-set information., Results: Using a composite gene-set analysis method, we combine the information of transcription factor binding sites, Gene Ontology or pathway gene sets and gene expression fold-change profiles for a variety of cell conditions. We then collected all the significant patterns and constructed a database of context-specific transcription networks for human (REGNET). As a result, context-specific roles of transcription factors as well as their functional targets are readily explored. To validate the approach, nine predicted targets of E2F1 in HeLa cells were tested using chromatin immunoprecipitation assay. Among them, five (Gadd45b, Dusp6, Mll5, Bmp2 and E2f3) were successfully bound by E2F1. c-JUN and the EMT transcription networks were also validated from literature., Conclusions: REGNET is a useful tool for exploring the ternary relationships among the transcription factors, their functional targets and the corresponding cell conditions. It is able to provide useful clues for novel cell-specific transcriptional regulations. The REGNET database is available at http://mgrc.kribb.re.kr/regnet.

In the title adduct, C11H11N3O·C2H4O2, all non-H atoms of the acetamide mol-ecule are roughly coplanar, with an r.m.s. deviation of 0.0720 Å. The dihedral angle between the ring plane and the acetamide group is 8.5 (2)°. In the crystal, O-H⋯N and N-H⋯O hydrogen bonds link the acetamide and acetic acid mol-ecules.

In the title co-crystal, C(12)H(11)Br(2)N(3)O·C(4)H(5)NO(2), the naphthyridine derivative and the pyrrolidine-2,5-dione mol-ecules have crystallographic mirror-plane symmetry with all non-H atoms, except the Br atom, located on the mirror plane. In the crystal, N-H⋯N, N-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into heterodimers. These dimers are further linked into a one-dimensional structure along [010] by weak C-Br⋯O inter-actions [Br⋯O = 3.028 (5) Å and C-Br⋯O = 158.52 (4)°].

Cancer has been considered to be the result of accumulated gene mutations, which result in uncontrolled cell proliferations for a long time. Cancers are also regarded to be capable of immune evasion. Furthermore, resistance to apoptosis was recognized as an important trait of cancer in the last score of years. However, there are numerous paradoxical issues in this whole set of theory. For example, there is no known set of genes of which mutations are responsible for human cancers. As for the trait of 'resistance to apoptosis', the fact is that cancer has increased frequency of apoptosis. The more malignant the tumour is, the more apoptosis shows. In this study, we propose a new theory that apoptosis plays a key role in the malignant progression and metastasis of cancer. The growth of tumour is the difference between tumour cell proliferation and attrition plus the hyperplastic growth of stroma. Increased and unpreventable death caused by innate or environmental factors such as ischaemia and inflammation drives the tumour cells to proliferate relentlessly, move to new lands to establish colonies. In short, increased cell death is the origin of malignancy., (© 2012 The Authors. Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.)

Summary: We present an accurate and fast web server, WegoLoc for predicting subcellular localization of proteins based on sequence similarity and weighted Gene Ontology (GO) information. A term weighting method in the text categorization process is applied to GO terms for a support vector machine classifier. As a result, WegoLoc surpasses the state-of-the-art methods for previously used test datasets. WegoLoc supports three eukaryotic kingdoms (animals, fungi and plants) and provides human-specific analysis, and covers several sets of cellular locations. In addition, WegoLoc provides (i) multiple possible localizations of input protein(s) as well as their corresponding probability scores, (ii) weights of GO terms representing the contribution of each GO term in the prediction, and (iii) a BLAST E-value for the best hit with GO terms. If the similarity score does not meet a given threshold, an amino acid composition-based prediction is applied as a backup method., Availability: WegoLoc and User's guide are freely available at the website http://www.btool.org/WegoLoc, Contact: smchiks@ks.ac.kr; dougnam@unist.ac.kr, Supplementary Information: Supplementary data is available at http://www.btool.org/WegoLoc.

ADGO 2.0 is a web-based tool that provides composite interpretations for microarray data comparing two sample groups as well as lists of genes from diverse sources of biological information. Some other tools also incorporate composite annotations solely for interpreting lists of genes but usually provide highly redundant information. This new version has the following additional features: first, it provides multiple gene set analysis methods for microarray inputs as well as enrichment analyses for lists of genes. Second, it screens redundant composite annotations when generating and prioritizing them. Third, it incorporates union and subtracted sets as well as intersection sets. Lastly, users can upload their own gene sets (e.g. predicted miRNA targets) to generate and analyze new composite sets. The first two features are unique to ADGO 2.0. Using our tool, we demonstrate analyses of a microarray dataset and a list of genes for T-cell differentiation. The new ADGO is available at http://www.btool.org/ADGO2.

The effect of compound nutrients on serum concentrations of the cytokines, such as interleukin (IL)-2, tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 in immobilization and cold water-immersion stressed rat were investigated. Oral (gavage) administration of compound nutrients was found to attenuate the acute and chronic immobilization and cold water-immersion stress-induced increase in serum IL-6 level and decrease in IL-2 level. Compound nutrients exerted different effects on TNF-alpha level in two different models studied, with reduced serum TNF-alpha level in acute stress, while no significant effect in chronic stress. These results suggested that compound nutrients might be proposed as a possible candidate in the research or therapeutic modulation of stress-related disorders.

Human erythropoietin gene expression in liver and kidney is inducible by anemia or hypoxia. DNase I-hypersensitive sites were identified 3' to the human erythropoietin gene in liver nuclei. A 256-base-pair region of 3' flanking sequence was shown by DNase I protection and electrophoretic mobility-shift assays to bind four or more different nuclear factors, at least two of which are induced by anemia in both liver and kidney, and the region functioned as a hypoxia-inducible enhancer in transient expression assays. These results provide insight into the molecular basis for the regulation of gene expression by a fundamental physiologic stimulus, hypoxia.