Phylogenetic Tree Analysis of the Cold-Hot Nature of Traditional Chinese Marine Medicine for Possible Anticancer Activity

Traditional Chinese Marine Medicine (TCMM) represents one of the medicinal resources for research and development of novel anticancer drugs. In this study, to investigate the presence of anticancer activity (AA) displayed by cold or hot nature of TCMM, we analyzed the association relationship and the distribution regularity of TCMMs with different nature (613 TCMMs originated from 1,091 species of marine organisms) via association rules mining and phylogenetic tree analysis. The screened association rules were collected from three taxonomy groups: (1) Bacteria superkingdom, Phaeophyceae class, Fucales order, Sargassaceae family, and Sargassum genus; (2) Viridiplantae kingdom, Streptophyta phylum, Malpighiales class, and Rhizophoraceae family; (3) Holothuroidea class, Aspidochirotida order, and Holothuria genus. Our analyses showed that TCMMs with closer taxonomic relationship weremore likely to possess anticancer bioactivity.We found that the cluster pattern ofmarine organisms with reported AA tended to cluster with cold nature TCMMs. Moreover, TCMMs with salty-cold nature demonstrated properties for softening hard mass and removing stasis to treat cancers, and species withinMetazoa orViridiplantae kingdomof cold natureweremore likely to contain AA properties.We propose that TCMMs from these marine groups may enable focused bioprospecting for discovery of novel anticancer drugs derived from marine bioresources

Global Mapping of Traditional Chinese Medicine into Bioactivity Space and Pathways Annotation Improves Mechanistic Understanding and Discovers Relationships between Therapeutic Action (Sub)classes.

Traditional Chinese medicine (TCM) still needs more scientific rationale to be proven for it to be accepted further in the West. We are now in the position to propose computational hypotheses for the mode-of-actions (MOAs) of 45 TCM therapeutic action (sub)classes from in silico target prediction algorithms, whose target was later annotated with Kyoto Encyclopedia of Genes and Genomes pathway, and to discover the relationship between them by generating a hierarchical clustering. The results of 10,749 TCM compounds showed 183 enriched targets and 99 enriched pathways from Estimation Score ≤ 0 and ≥ 5% of compounds/targets in a (sub)class. The MOA of a (sub)class was established from supporting literature. Overall, the most frequent top three enriched targets/pathways were immune-related targets such as tyrosine-protein phosphatase nonreceptor type 2 (PTPN2) and digestive system such as mineral absorption. We found two major protein families, G-protein coupled receptor (GPCR), and protein kinase family contributed to the diversity of the bioactivity space, while digestive system was consistently annotated pathway motif, which agreed with the important treatment principle of TCM, "the foundation of acquired constitution" that includes spleen and stomach. In short, the TCM (sub)classes, in many cases share similar targets/pathways despite having different indications.Peer Reviewe

Proteomic analysis of differential proteins in pancreatic carcinomas: Effects of MBD1 knock-down by stable RNA interference

<p>Abstract</p> <p>Background</p> <p>Methyl-CpG binding domain protein 1 (MBD1), a suppressor of gene transcription, may be involved in inactivation of tumor suppressor genes during tumorigenesis. Over-expression of MBD1 has been reported in human pancreatic carcinomas.</p> <p>Methods</p> <p>In this study, we established a MBD1-knock-down pancreatic cancer cell line (BxPC-3) using stable RNA interference, to compare the proteomic changes between control and MBD1-knock-down cells using two-dimensional gel electrophoresis and mass spectrometry.</p> <p>Results</p> <p>We identified five proteins that were up-regulated and nine proteins that were down-regulated. Most of the identified proteins are involved in tumorigenesis, some are prognostic biomarkers for human malignant tumors.</p> <p>Conclusion</p> <p>Our data suggest that these differential proteins may be associated with the function of MBD1, and provide some insight into the functional mechanism of MBD1 in the development of pancreatic cancer.</p

Danshen Formulae for Cancer: A Systematic Review and Meta-Analysis of High-Quality Randomized Controlled Trials

Objective. Cancer is one of the most dangerous diseases to human life and there is no radical cure for it. In this paper, we compiled quantities of case history to evaluate the current available evidence of herbal Danshen (Radix Salviae Miltiorrhizae, RSM) formulae for the treatment of cancer by means of the high-quality randomized controlled trials (RCTs). Methods. English and Chinese electronic databases were searched from PubMed, the Cochrane Library, EMBASE, and the China National Knowledge Infrastructure (CNKI), VIP database, Wanfang database until September 2018. The methodological quality of the included studies was evaluated by using the method of Cocharne evidence-based medicine system evaluation, the quality was evaluated by screening the literature that met the requirements, and the Review Manager 5.3 was used for statistical analysis. The pooled odds ratio (OR) with 95% CIs was used to estimate the correlation between Danshen formulae and therapeutic effects. Results. Thirteen RCTs with 1045 participants were identified. The studies investigated the lung cancer (n = 5), leukemia (n = 3), liver cancer (n = 3), breast or colon cancer (n = 1), and gastric cancer (n = 1). A total of 83 traditional Chinese medicines were used in all prescriptions and there were 3 different dosage forms. Meta-analysis suggested that Danshen formulae had a significant effect on RR (response rate) (OR 2.38, 95% CI 1.66-3.42), 1-year survival (OR 1.70 95% CI 1.22-2.36), 3-year survival (OR 2.78, 95% CI 1.62-4.78), and 5-year survival (OR 8.45, 95% CI 2.53-28.27). Conclusion. The current research results showed that Danshen formulae combined with chemotherapy for cancer treatment was better than conventional drug treatment plan alone

Development of a Preliminary Design Method for Subsonic Splittered Blades in Highly Loaded Axial-Flow Compressors

This paper presents a model for predicting the reference minimum-loss incidence and deviation angles of a blade arrangement with splitter vanes, which is probably a solution for future ultra-highly loaded axial compressor designs. The motivation of the modeling is to guide the blading design in splittered compressor design processes where the additional splitter vanes must be specially considered. The development of the model is based on a blade performance database from systematic numerical simulations. Basic correlations of the model are firstly proposed, which consider dominant blade geometry parameters related to blade loading, including camber angle and solidity. Secondly, geometric and aerodynamic corrections about orientation parameter, blade maximum thickness, inlet Mach number, and three-dimensional (3D) effects are empirically incorporated into the basic correlations. Eventually, a subsonic 3D splittered rotor is designed using the correlations coupled with the corrections obtained from the validation of the model. The results indicate that the model is able to achieve a good agreement within an error band of ±1.0° for the predictions of both reference minimum-loss incidence and deviation angles, and the rotor designed using the model accomplishes the desired work input and flow deflection

Effects of Farnesiferol B on Ischemia-Reperfusion-Induced Renal Damage, Inflammation, and NF-κB Signaling

Background: G-protein-coupled bile acid receptor (TGR5), a membrane bile acid receptor, regulates macrophage reactivity, and attenuates inflammation in different disease models. However, the regulatory effects of TGR5 in ischemia/reperfusion (I/R)-induced kidney injury and inflammation have not yet been extensively studied. Therefore, we hypothesize that Farnesiferol B, a natural TGR5 agonist, could alleviate renal I/R injury by reducing inflammation and macrophage migration through activating TGR5. Methods: Mice were treated with Farnesiferol B before I/R or sham procedures. Renal function, pathological analysis, and inflammatory mediators were examined. In vitro, the regulatory effects of Farnesiferol B on the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in macrophages were investigated. Results: After I/R, Farnesiferol B-treated mice displayed better renal function and less tubular damage. Farnesiferol B reduced renal oxidative stress and inflammation significantly. In vitro, Farnesiferol B treatment alleviated lipopolysaccharide (LPS)-induced macrophage migration and activation, as well as LPS-induced NF-κB activation through TGR5. Conclusions: Farnesiferol B could protect kidney function from I/R-induced damage by attenuating inflammation though activating TGR5 in macrophages. Farnesiferol B might be a potent TGR5 ligand for the treatment of I/R-induced renal inflammation