Gene selection for cancer identification: a decision tree model empowered by particle swarm optimization algorithm.

BACKGROUND: In the application of microarray data, how to select a small number of informative genes from thousands of genes that may contribute to the occurrence of cancers is an important issue. Many researchers use various computational intelligence methods to analyzed gene expression data. RESULTS: To achieve efficient gene selection from thousands of candidate genes that can contribute in identifying cancers, this study aims at developing a novel method utilizing particle swarm optimization combined with a decision tree as the classifier. This study also compares the performance of our proposed method with other well-known benchmark classification methods (support vector machine, self-organizing map, back propagation neural network, C4.5 decision tree, Naive Bayes, CART decision tree, and artificial immune recognition system) and conducts experiments on 11 gene expression cancer datasets. CONCLUSION: Based on statistical analysis, our proposed method outperforms other popular classifiers for all test datasets, and is compatible to SVM for certain specific datasets. Further, the housekeeping genes with various expression patterns and tissue-specific genes are identified. These genes provide a high discrimination power on cancer classification.

Resting salivary levels of IgA and cortisol are significantly affected during intensive resistance training periods in elite male weightlifters.

The aim of this study was to investigate the cumulative effects of intensive resistance training on salivary immunoglobulin A (SIgA) and cortisol responses in elite male weightlifters. Eleven elite male Taiwanese weightlifters were trained through 3 training stages before a national weightlifting competition, and this was followed by a 2-week recovery stage. Resting saliva samples were collected once in each of the 4 stages. Salivary concentrations of total protein (TP), SIgA, lactoferrin, and cortisol were measured. The results showed that (a) salivary TP concentrations were not significantly affected; (b) resting levels of SIgA, the ratio of SIgA to TP (SIgA/TP), cortisol, and the ratio of cortisol to TP (cortisol/TP) were significantly higher in the training stages than in the recovery stage; (c) a positive correlation was revealed between the ratios of SIgA/TP and cortisol/TP; and (d) the resting salivary lactoferrin concentrations and the ratio of lactoferrin to TP (lactoferrin/TP) were significantly lower in stage 1 than in the recovery stage. The findings in this study suggest that prolonged, intensive resistance training exerts cumulative effects on SIgA and cortisol responses in elite weightlifters.

Honokiol inhibits LPS-induced maturation and inflammatory response of human monocyte-derived dendritic cells.

Honokiol (HNK) is a phenolic compound isolated from the bark of houpu (Magnolia officinalis), a plant widely used in traditional Chinese and Japanese medicine. While substantial evidence indicates that HNK possesses anti-inflammatory activity, its effect on dendritic cells (DCs) during the inflammatory reaction remains unclear. The present study investigates how HNK affects lipopolysaccharide (LPS)-stimulated human monocyte-derived DCs. Our experimental results show that HNK inhibits the inflammatory response of LPS-induced DCs by (1) suppressing the expression of CD11c, CD40, CD80, CD83, CD86, and MHC-II on LPS-activated DCs, (2) reducing the production of TNF-α, IL-1ß, IL-6, and IL-12p70 but increasing the production of IL-10 and TGF-ß1 by LPS-activated DCs, (3) inhibiting the LPS-induced DC-elicited allogeneic T-cell proliferation, and (4) shifting the LPS-induced DC-driven Th1 response toward a Th2 response. Further, our results show that HNK inhibits the phosphorylation levels of ERK1/2, p38, JNK1/2, IKKα, and IκBα in LPS-activated DCs. Collectively, the findings show that the anti-inflammatory actions of HNK on LPS-induced DCs are associated with the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways.

Microarray meta-analysis database (M(2)DB): a uniformly pre-processed, quality controlled, and manually curated human clinical microarray database.

BACKGROUND: Over the past decade, gene expression microarray studies have greatly expanded our knowledge of genetic mechanisms of human diseases. Meta-analysis of substantial amounts of accumulated data, by integrating valuable information from multiple studies, is becoming more important in microarray research. However, collecting data of special interest from public microarray repositories often present major practical problems. Moreover, including low-quality data may significantly reduce meta-analysis efficiency. RESULTS: M2DB is a human curated microarray database designed for easy querying, based on clinical information and for interactive retrieval of either raw or uniformly pre-processed data, along with a set of quality-control metrics. The database contains more than 10,000 previously published Affymetrix GeneChip arrays, performed using human clinical specimens. M2DB allows online querying according to a flexible combination of five clinical annotations describing disease state and sampling location. These annotations were manually curated by controlled vocabularies, based on information obtained from GEO, ArrayExpress, and published papers. For array-based assessment control, the online query provides sets of QC metrics, generated using three available QC algorithms. Arrays with poor data quality can easily be excluded from the query interface. The query provides values from two algorithms for gene-based filtering, and raw data and three kinds of pre-processed data for downloading. CONCLUSION: M2DB utilizes a user-friendly interface for QC parameters, sample clinical annotations, and data formats to help users obtain clinical metadata. This database provides a lower entry threshold and an integrated process of meta-analysis. We hope that this research will promote further evolution of microarray meta-analysis.

Relationships among salivary immunoglobulin A, lactoferrin and cortisol in basketball players during a basketball season.

The aim of this study was to examine the changes and relationships of immune and stress parameters of basketball players during a basketball season. Eight members of National Taichung University basketball team volunteered to participate. Saliva samples were collected at rest and before the start of practice or competition at seven time points during the intense training, competition and recovery period. Salivary immunoglobulin A (sIgA), cortisol, and lactoferrin were measured during training and competition period and compared with those measured at the fourth recovery week. Relationships among immune and stress parameters were evaluated. Compared with those detected at the fourth recovery week, significant decreases in secretion rates and absolute concentrations of sIgA and lactoferrin were observed at times of intense training and competition. In addition, significant increases in secretion rates and absolute concentrations of salivary cortisol were observed during intense training and competition period and the first week of recovery. Moreover, a significant inverse correlation (r = -0.28; P < 0.05) that existed between secretion rates of sIgA and cortisol as well as a positive correlation (r = 0.32; P < 0.05) that existed between secretion rates of sIgA and lactoferrin was measured. Our results demonstrated that the secreted cortisol was induced and the mucosal immunity of the participants was suppressed during the basketball season. The inverse correlation existed between secretion rates of sIgA and cortisol may indicate a possible role of cortisol in the strenuous exercise-induced immunosuppression. Our results also suggest that a delicate balance may exist between mucosal innate and adaptive immune responses.

Index of Cancer-Associated Fibroblasts Is Superior to the Epithelial-Mesenchymal Transition Score in Prognosis Prediction.

In many solid tumors, tissue of the mesenchymal subtype is frequently associated with epithelial-mesenchymal transition (EMT), strong stromal infiltration, and poor prognosis. Emerging evidence from tumor ecosystem studies has revealed that the two main components of tumor stroma, namely, infiltrated immune cells and cancer-associated fibroblasts (CAFs), also express certain typical EMT genes and are not distinguishable from intrinsic tumor EMT, where bulk tissue is concerned. Transcriptomic analysis of xenograft tissues provides a unique advantage in dissecting genes of tumor (human) or stroma (murine) origins. By transcriptomic analysis of xenograft tissues, we found that oral squamous cell carcinoma (OSCC) tumor cells with a high EMT score, the computed mesenchymal likelihood based on the expression signature of canonical EMT markers, are associated with elevated stromal contents featured with fibronectin 1 (Fn1) and transforming growth factor-ß (Tgfß) axis gene expression. In conjugation with meta-analysis of these genes in clinical OSCC datasets, we further extracted a four-gene index, comprising FN1, TGFB2, TGFBR2, and TGFBI, as an indicator of CAF abundance. The CAF index is more powerful than the EMT score in predicting survival outcomes, not only for oral cancer but also for the cancer genome atlas (TCGA) pan-cancer cohort comprising 9356 patients from 32 cancer subtypes. Collectively, our results suggest that a further distinction and integration of the EMT score with the CAF index will enhance prognosis prediction, thus paving the way for curative medicine in clinical oncology.

UVB radiation induces persistent activation of ribosome and oxidative phosphorylation pathways.

Ultraviolet B (UVB) radiation has strong biological effects and modulates the expression of many genes. The major biological pathways affected by UVB radiation remain controversial. In this work, we used a loop-design microarray approach and applied rigorous statistical analyses to identify differentially regulated genes at 4, 8, 16 or 24 h after UVB irradiation. The most prominent biological categories in lists of differentially regulated gene sets were extracted by functional enrichment analysis. With this approach, we determined that genes participating in two prime cellular processes, the ribosome pathway and the oxidative phosphorylation pathway, were persistently activated after UVB irradiation. Mitochondrial activity assays confirmed increased activity for up to 24 h after UVB irradiation. These results suggest that the persistent activation of ribosome and oxidative phosphorylation pathways may have a key role in UVB-radiation-induced cellular responses. For the first time, the specific cellular pathways that respond to UVB radiation consistently and persistently can be delineated with confidence using a loop-design microarray approach and functional bioinformatics analysis. The results of this study offer further insight into UVB-radiation-induced stress responses.

Cordyceps sinensis health supplement enhances recovery from taxol-induced leukopenia.

This study aimed to evaluate the ability of the health food supplement Cordyceps sinensis (CS) to ameliorate suppressive effects of chemotherapy on bone marrow function as a model for cancer treatment. Mice were treated with Taxol (17 mg/kg body wt) one day before oral administration of a hot-water extract of CS (50 mg/kg daily) that was given daily for 3 weeks. White blood cell counts in peripheral blood of mice receiving Taxol were at 50% of normal levels on day 28 but had recovered completely in mice treated with CS. In vitro assays showed that CS enhanced the colony-forming ability of both granulocyte macrophage colony forming unit (GM-CFU) and osteogenic cells from bone marrow preparations and promoted the differentiation of bone marrow mesenchymal stromal cells into adipocytes, alkaline phosphatase-positive osteoblasts, and bone tissue. This result could be attributed to enhanced expression of Cbfa1 (core binding factor a) and BMP-2 (bone morphogenetic protein) with concurrent suppression of ODF (osteoclast differentiation factor/RANK [receptor activator of NF-kappaB]) ligand. In summary, CS enhances recovery of mice from leukopenia caused by Taxol treatment. It appears to do so by protecting both hematopoietic progenitor cells directly and the bone marrow stem cell niche through its effects on osteoblast differentiation.

Protection against radiation-induced bone marrow and intestinal injuries by Cordyceps sinensis, a Chinese herbal medicine.

Bone marrow and intestinal damage limits the efficacy of radiotherapy for cancer and can result in death if the whole body is exposed to too high a dose, as might be the case in a nuclear accident or terrorist incident. Identification of an effective nontoxic biological radioprotector is therefore a matter of some urgency. In this study, we show that an orally administered hot-water extract from a Chinese herbal medicine, Cordyceps sinensis (CS), protects mice from bone marrow and intestinal injuries after total-body irradiation (TBI). CS increased the median time to death from 13 to 20 days after 8 Gy TBI and from 9 to 18 days after 10 Gy TBI. Although CS-treated mice receiving 10 Gy TBI survived intestinal injury, most died from bone marrow failure, as shown by severe marrow hypoplasia in mice dying between 18 and 24 days. At lower TBI doses of 5.5 and 6.5 Gy, CS protected against bone marrow death, an effect that was confirmed by the finding that white blood cell counts recovered more rapidly. In vitro, CS reduced the levels of free radical species (ROS) within cells, and this is one likely mechanism for the radioprotective effects of CS, although probably not the only one.

The bradykinin/soluble guanylate cyclase signaling pathway is impaired in androgen-independent prostate cancer cells.

The activation of soluble guanylate cyclase by bradykinin and sodium nitroprusside (SNP), a direct activator of soluble guanylate cyclase, was evaluated in androgen-sensitive LNCaP and androgen-independent PC3 and DU145 prostate cancer cells. Bradykinin and SNP activated soluble guanylate cyclase in LNCaP cells, but not in PC3 and DU145 cells. Western blot analysis revealed that the bradykinin B2 receptor, Gqalpha, phospholipase Cgamma and endothelial nitric oxide synthase were expressed in LNCaP, PC3 and DU145 cells. However, both Western blotting and reverse transcriptase--polymerase chain reaction indicated that soluble guanylate cyclase was only expressed in LNCaP cells. These results demonstrate that the impaired bradykinin-soluble guanylate cyclase pathway in PC3 and DU145 cells is likely due to lack of expression of soluble guanylate cyclase.