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Background: Sugarcane smut caused by Sporisorium scitamineum leads to a significant reduction in cane yield and sucrose content. MicroRNAs (miRNAs) play an important role in regulating plant responses to biotic stress. The present study was the first to use two sugarcane genotypes, YA05-179 (smut-resistant) and ROC22 (smut-susceptible), to identify differentially expressed miRNAs in sugarcane challenged with S. scitamineum by using high-throughput sequencing. Results: The predicted target gene number corresponding to known differentially expressed miRNAs in YA05-179 was less than that in ROC22, however most of them were in common. Expression of differential miRNAs under S. scitamineum challenge was mostly downregulated, with similar trends in the two varieties. Gene ontology (GO) analysis showed that the target gene classification of known miRNAs was similar to that of the newly identified miRNAs. These were mainly associated with cellular processes and metabolic processes in the biological process category, as well as combination and catalytic activity in the molecular function category. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these predicted target genes involved in a series of physiological and biochemical pathways or disease resistance-related physiological metabolism and signal transduction pathways, suggesting that the molecular interaction mechanism between sugarcane and S. scitamineum was a complex network system. These findings also showed certain predicted target genes of miR5671, miR5054, miR5783, miR5221, and miR6478 play roles in the mitogen-activated protein kinase (MAPK) signaling pathway, plant hormone signal transduction, and plant-pathogen interaction. Quantitative real-time PCR (qRT-PCR) analysis showed that majority of the known miRNAs and its predicted target genes followed a negatively regulated mode. Seven out of eight predicted target genes showed identical expression after 12 h treatment and reached the highest degree of matching at 48 h, indicating that the regulatory role of miRNAs on the target genes in sugarcane was maximized at 48 h after S. scitamineum challenge. Conclusions: Taken together, our findings serve as evidence for the association of miRNA expression with the molecular mechanism underlying the pathogenesis of sugarcane smut, particularly on the significance of miRNA levels in relation to the cultivation of smut-resistant sugarcane varieties. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) have great potential serving as tumor biomarkers and therapeutic targets. As the rapid development of high-throughput experimental technology, gene expression experiments have become more and more specialized and diversified. The complex data structure has brought great challenge for the identification of biomarkers. In the meantime, current statistical and machine learning methods for detecting biomarkers have the problem of low reliability and biased criteria. Results: This study aims to select combinatorial miRNA biomarkers, which have higher sensitivity and specificity than single-gene biomarkers. In order to avoid exhaustive search and redundant information, miRNAs are firstly clustered, then the combinations of representative cluster members are assessed as potential biomarkers. Both the criteria for the partition of clusters and selection of representative members are based on Fisher linear discriminant analysis (FDA). The FDA-based criterion has been demonstrated to be superior to three other criteria in selecting representative members, and also good at refining clusters. In the comparison with eight common feature selection methods, this clustering-based method performs the best with regard to the discriminative ability of selected biomarkers. Conclusions: Our experimental results demonstrate that the clustering-based method can identify microRNA combinatorial biomarkers with high accuracy and efficiency. Our method and data are available to the public upon request. [ABSTRACT FROM AUTHOR]

Background: Anterior cervical discectomy and fusion (ACDF) is widely used in the treatment of cervical degenerative disease; however, the variation of cervical sagittal alignment changes after ACDF has been rarely explored. The purpose of this study is to determine the relationship between changes of cervical sagittal alignment after ACDF and spino-pelvic sagittal alignment under Roussouly classification.Methods: A cohort of 133 Chinese cervical spondylotic patients who received ACDF from 2011 to 2012 was recruited. All patients were categorized with Roussouly Classification. Lateral X-ray images of global spine were obtained, and preoperative and postoperative parameters were measured and analyzed, including C2-C7 angles (C2-C7), C0-C7 angles (C0-C7), external auditory meatus (EAM) tilt, sacral slope (SS), thoracic kyphosis (TK), lumbar lordosis (LL), spinal sacral angles (SSA), Superior adjacent inter-vertebral angle (SAIV), inferior adjacent inter-vertebral angle (IAIV) and et al. The Wilcoxon signed-rank test was used for intragroup comparisons preoperatively and at postoperative 48 months.Results: Among the parameters, C2-C7 and C0-C7 showed significant increase, while EAM TK, and IAIV decreased significantly. In type I, EAM and TK decreased significantly, however SS showed a significant increase; in type II, TK showed a significant decrease, but SSA showed a significant increase; in type III, a significant increase of C0-C7 was observed with a significant decrease in EAM, nevertheless, LL, SS and SSA showed significant decreases; and in type IV, C2-C7 showed a significant increase and EAM decreased significantly. The percentage of lordotic alignment in cervical spine increased, which was presenting in type I, III and IV. Nevertheless, the amount of patients with straight cervical alignment increased in type II.Conclusion: The backward movement of head occurs is the compensatory mechanism in cervical sagittal alignment modifications after ACDF. The compensatory alteration of spino-pelvic sagittal alignment varied in different Roussouly type. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs (lncRNAs) are related to different biological processes in non-small cell lung cancer (NSCLC). However, the possible molecular mechanisms underlying the effects of the long noncoding RNA HOXA11-AS (HOXA11 antisense RNA) in NSCLC are unknown. Methods: HOXA11-AS was knocked down in the NSCLC A549 cell line and a high throughput microarray assay was applied to detect changes in the gene profiles of the A549 cells. Bioinformatics analyses (gene ontology (GO), path- way, Kyoto Encyclopedia of Genes and Genomes (KEGG), and network analyses) were performed to investigate the potential pathways and networks of the differentially expressed genes. The molecular signatures database (MSigDB) was used to display the expression profiles of these differentially expressed genes. Furthermore, the relationships between the HOXA11-AS, de-regulated genes and clinical NSCLC parameters were verified by using NSCLC patient information from The Cancer Genome Atlas (TCGA) database. In addition, the relationship between HOXA11-AS expression and clinical diagnostic value was analyzed by receiver operating characteristic (ROC) curve. Results: Among the differentially expressed genes, 277 and 80 genes were upregulated and downregulated in NSCLC, respectively (fold change ≥2.0, P < 0.05 and false discovery rate (FDR) < 0.05). According to the degree of the fold change, six upregulated and three downregulated genes were selected for further investigation. Only four genes (RSPO3, ADAMTS8, DMBT1, and DOCK8) were reported to be related with the development or progression of NSCLC based on a PubMed search. Among all possible pathways, three pathways (the PI3K-Akt, TGF-beta and Hippo signaling pathways) were the most likely to be involved in NSCLC development and progression. Furthermore, we found that HOXA11-AS was highly expressed in both lung adenocarcinoma and squamous cell carcinoma based on TCGA database. The ROC curve showed that the area under curve (AUC) of HOXA11-AS was 0.727 (95% CI 0.663-0.790) for lung adenocarcinoma and 0.933 (95% CI 0.906-0.960) for squamous cell carcinoma patients. Additionally, the original data from TCGA verified that ADAMTS8, DMBT1 and DOCK8 were downregulated in both lung adenocarcinoma and squamous cell carcinoma, whereas RSPO3 expression was upregulated in lung adenocarcinoma and downregulated in lung squamous cell carcinoma. For the other five genes (STMN2, SPINK6, TUSC3, LOC100128054, and C8orf22), we found that STMN2, TUSC3 and C8orf22 were upregulated in squamous cell carcinoma and that STMN2 and USC3 were upregulated in lung adenocarcinoma. Furthermore, we compared the correlation between HOXA11-AS and de-regulated genes in NSCLC based on TCGA. The results showed that the HOXA11-AS expression was negatively correlated with DOCK8 in squamous cell carcinoma (r = -0.124, P = 0.048) and lung adenocarcinoma (r = -0.176, P = 0.005). In addition, RSPO3, ADAMTS8 and DOCK8 were related to overall survival and disease-free survival (all P < 0.05) of lung adenocarcinoma patients in TCGA. Conclusions: Our results showed that the gene proiles were signiicantly changed after HOXA11-AS knock-down in NSCLC cells. We speculated that HOXA11-AS may play an important role in NSCLC development and progression by regulating the expression of various pathways and genes, especially DOCK8 and TGF-beta pathway. However, the exact mechanism should be veriied by functional experiments. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma (OS) is well-known for poor prognosis due to its high incidence of proliferation and metastasis. Researches have provided valuable insights into the tumorigenesis of S100A9 in some cancers. We aimed to understand the expression level, functions and mechanisms of S100A9 in human osteosarcoma for the first time.Methods: The expression of S100A9 protein was detected in 120 human osteosarcoma tissues and 40 normal human bone tissues using tissue microarrays analysis. The knockdown of S100A9 induced by RNA interference (RNAi) method in three osteosarcoma cell lines (U2OS, 143B, MG63) was applied to analyze the effects of S100A9 on cell proliferation, cell cycle distribution, migration, invasion and xenotransplanted tumors. Moreover, MAPK-ERK1/2, MAPK-p38, NF-κB-p65, NF-κB-p50, p21, p27, CDK2 and CDK4 were tested.Results: The expression of S100A9 was increased in human osteosarcoma issues and was positively correlated with clinical classification and survival rate. Down-regulation of S100A9 inhibited OS cellular proliferation, migration, invasion and cell cycle S phase in vitro and suppressed tumor formation in vivo with the reduction on PCNA and Ki67 proliferation index. Our data also demonstrated that knockdown of S100A9 repressed the protein levels of phospho-ERK1/2, phospho-p50, phospho-p65 except phospho-p38, and prompted up-regulation of p21 and p27 leading to inactivation of cyclin dependent kinase 2(CDK2) and cyclin dependent kinase 4(CDK4).Conclusions: S100A9 might be a significant role for predicting osteosarcoma prognosis and down-regulation of S100A9 could be used as a potential target for gene therapy. [ABSTRACT FROM AUTHOR]

Background: YKL-40 is a secreted inflammatory protein that its overexpression has been reported to correlate with poor outcome of various malignant diseases, especially in cancer. However, the function of this protein is still unclear. Methods: The clinical prognosis of non-small cell lung cancers (NSCLC) patients and their clinical YKL-40 expressions were obtained from the Prognoscan database. The expressions of YKL-40 in patient samples were determined by Western Blotting assay. YKL-40 gene knockdown and overexpression were performed on NSCLC cancer cells (CL1-1 and CL1-5). The cells were investigated for their epithelial-mesenchymal transition (EMT) markers gene modulation through Western Blotting and RT-PCR. Further cell metastatic abilities were assessed by transwell migration and invasion assay. Result: In this study, YKL-40 was observed to be highly expressed in NSCLC specimens. Furthermore, determined by the PrognoScan database analysis, patients with high expression levels of YKL-40 were found with poor prognosis. In the in vitro study, different characteristics of NSCLC cell lines (CL1-1, H23, H838, CL1-5, and H2009) were used as study models, where YKL-40 expression levels were determined to correlate with the phenotypic characteristics of cancer metastasis. In this study, YKL-40 was demonstrated to regulate EMT marker expressions such as Twist, Snail, Slug, N-cadherin, Vimentin, and E-cadherin. The protein's affects in cancer cell migration and invasion were also observed in YKL-40 overexpression or knock down NSCLC cell lines. Conclusion: All of results from this study suggest that YKL-40 is a major factor in NSCLC metastasis. Thus, YKL-40 may serve as therapeutic target for NSCLC patients in the future. [ABSTRACT FROM AUTHOR]

Introduction: Zellweger spectrum disorder (PBD-ZSD) is a disease continuum caused by mutations in a subset of PEX genes required for normal peroxisome assembly and function. They highlight the importance of peroxisomes in the development and functions of the central nervous system, liver, and other organs. To date, the underlying bases for the cell-type specificity of disease are not fully elucidated. Methods: Primary skin fibroblasts from seven PBD-ZSD patients with biallelic PEX1, PEX10, PEX12, or PEX26 mutations and three healthy donors were transduced with retroviral vectors expressing Yamanaka reprogramming factors. Candidate induced pluripotent stem cells (iPSCs) were subject to global gene expression, DNA methylation, copy number variation, genotyping, in vitro differentiation and teratoma formation assays. Confirmed iPSCs were differentiated into neural progenitor cells (NPCs), neurons, oligodendrocyte precursor cells (OPCs), and hepatocyte-like cell cultures with peroxisome assembly evaluated by microscopy. Saturated very long chain fatty acid (sVLCFA) and plasmalogen levels were determined in primary fibroblasts and their derivatives. Results: iPSCs were derived from seven PBD-ZSD patient-derived fibroblasts with mild to severe peroxisome assembly defects. Although patient and control skin fibroblasts had similar gene expression profiles, genes related to mitochondrial functions and organelle cross-talk were differentially expressed among corresponding iPSCs. Mitochondrial DNA levels were consistent among patient and control fibroblasts, but varied among all iPSCs. Relative to matching controls, sVLCFA levels were elevated in patient-derived fibroblasts, reduced in patient-derived iPSCs, and not significantly different in patient-derived NPCs. All cell types derived from donors with biallelic null mutations in a PEX gene showed plasmalogen deficiencies. Reporter gene assays compatible with high content screening (HCS) indicated patient-derived OPC and hepatocyte-like cell cultures had impaired peroxisome assembly. Conclusions: Normal peroxisome activity levels are not required for cellular reprogramming of skin fibroblasts. Patient iPSC gene expression profiles were consistent with hypotheses highlighting the role of altered mitochondrial activities and organelle cross-talk in PBD-ZSD pathogenesis. sVLCFA abnormalities dramatically differed among patient cell types, similar to observations made in iPSC models of X-linked adrenoleukodystrophy. We propose that iPSCs could assist investigations into the cell type-specificity of peroxisomal activities, toxicology studies, and in HCS for targeted therapies for peroxisome-related disorders. [ABSTRACT FROM AUTHOR]

Background: YKL-40 is a secreted inflammatory protein that its overexpression has been reported to correlate with poor outcome of various malignant diseases, especially in cancer. However, the function of this protein is still unclear. Methods: The clinical prognosis of non-small cell lung cancers (NSCLC) patients and their clinical YKL-40 expressions were obtained from the Prognoscan database. The expressions of YKL-40 in patient samples were determined by Western Blotting assay. YKL-40 gene knockdown and overexpression were performed on NSCLC cancer cells (CL1-1 and CL1-5). The cells were investigated for their epithelial–mesenchymal transition (EMT) markers gene modulation through Western Blotting and RT-PCR. Further cell metastatic abilities were assessed by transwell migration and invasion assay. Result: In this study, YKL-40 was observed to be highly expressed in NSCLC specimens. Furthermore, determined by the PrognoScan database analysis, patients with high expression levels of YKL-40 were found with poor prognosis. In the in vitro study, different characteristics of NSCLC cell lines (CL1-1, H23, H838, CL1-5, and H2009) were used as study models, where YKL-40 expression levels were determined to correlate with the phenotypic characteristics of cancer metastasis. In this study,YKL-40 was demonstrated to regulate EMT marker expressions such as Twist, Snail, Slug, N-cadherin, Vimentin, and E-cadherin. The protein’s affects in cancer cell migration and invasion were also observed in YKL-40 overexpression or knock down NSCLC cell lines. Conclusion: All of results from this study suggest that YKL-40 is a major factor in NSCLC metastasis. Thus, YKL-40 may serve as therapeutic target for NSCLC patients in the future. [ABSTRACT FROM AUTHOR]

Background: Whether health literacy is independently associated with processes or outcomes of diabetes-related care is controversial. We tried to demonstrate the interaction of health literacy and understanding of health education and instructions in achieving glycemic control. Methods: Five hundred and one consecutive patients with type 2 diabetes mellitus (DM) in the outpatient clinic of the metabolism department were recruited into this pilot study. The demographic data were collected from patients’ self-reports. The clinical background information was collected through electronic medical records. A questionnaire derived from part of the Mandarin Health Literacy Scale was used to measure numeracy and functional health literacy of people with diabetes. Health literacy levels were categorized into inadequate, marginal and adequate. Patient self-ratings of their perceived understanding of the health education information and instructions provided by their case manager in the past were categorized into two subgroups: better and poor. Patients with an HbA1c level equal to or below 7% were considered to have good glycemic control. Multivariate logistic regression was used to find associated factors of health literacy and understanding of health education and instructions. GENMOD procedures were used to analyze repeated outcome measurements of glycemic control. Results: Higher educational attainment and higher household income (odds ratios were 2.23 and 2.22, respectively) were significantly associated with patients who had adequate health literacy. Higher educational attainment and patients with a family history of DM (odds ratios were 4.99 and 1.85, respectively) were significantly associated with better understanding of health education and instructions. Adequate health literacy is not the only factor associated with good glycemic control. The effect of adequate health literacy in achieving good glycemic control might be masked by patients with better understanding of health education and instructions. Conclusions: Our results revealed that not only were patients with adequate health literacy associated with good glycemic control but patients with marginal health literacy were also able to achieve good glycemic control. Adequate health literacy and better understanding of health education is highly correlated. The role of adequate health literacy on glycemic control could be suppressed if variables are over-controlled during analysis. [ABSTRACT FROM AUTHOR]

Background Isoflavone-containing soy products modulate allergic inflammation in mice. In our previously study, IFN-γ and IL-10 production increased in mice fed with Saccharomyces cerevisiae legume fermented product (SCLFP), demonstrating that SCLFP had immunomodulatory activity. In this study, we tested the anti-inflammatory effects of SCLFP in a mouse model of cutaneous atopic dermatitis inflammation induced by epicutaneous sensitization. Methods Epicutaneous exposure to protein allergens plus Staphylococcal enterotoxin B induced a T helper (Th)-2-dominant immune response as well as cutaneous atopic dermatitis-like inflammation in BALB/c mice. The thickness of the skin epithelium, eosinophil migration, and T helper responses were determined in patched skin and draining lymph nodes of mice fed with and without SCLFP. Results Epicutaneous exposure to protein allergens plus Staphylococcal enterotoxin B induced a T helper (Th)-2-dominant immune response as well as cutaneous atopic dermatitis-like inflammation in BALB/c mice. SCLFP feeding attenuated this cutaneous Th2 response, as evidenced by decreased thickening of the epidermis, less eosinophil infiltration, and lower levels of IL-5, IL-13, and CXCL11 expression compared to controls. Oral administration of SCLFP also modulated Th1 responses in draining lymph nodes, with lower levels of IFN-γ, IL-4, and IL-17 expression. Conclusion Oral intake of SCLFP modulated the induced Th2 inflammatory responses in skin and might have potential applications for the prevention and treatment of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Musculoskeletal disorders (MSDs) represent the leading causes of occupational injuries among nursing staff. This population-based study was designed to assess the incidence and age-specific incidence of MSDs among a Taiwanese nurse cohort compared with non-nurses. Description: Data from the Taiwan National Health Insurance Research Database were used to identify MSDs in the study population. A total of 3914 nurses with a diagnosis of MSD were included, together with 11,744 non-nurses as a comparison group. The comparison subjects were randomly selected at a ratio of 3:1 relative to the nurse population and were matched by gender and age. The incidence of MSDs was calculated for the study group, with nurse-to-reference risk ratios presented as odds ratios with 95% confidence intervals (CIs). During the period 2004- 2010, 3004 MSDs occurred among the nurses (76.24%) and 7779 (65.79%) in the non-nurses. The annual incidence of MSDs for the nurses increased from 28.35% in 2006 to 33.65% in 2010. The nurse-to-reference risk ratio was 1.27 (95% CI 1.19-1.35) in 2004 and 1.46 (1.37-1.55) in 2010. Herniation of intervertebral disc, lumbago, rotator cuff syndrome, medial epicondylitis, trigger finger and carpal tunnel syndrome were the most common problems. Conclusions: Nurses are at higher risk of MSDs and the trend is increasing. Incorrect work-related posture/ movement, psychological issues and the rolling shift system may be the major causes of MSDs among nurses in Taiwan. [ABSTRACT FROM AUTHOR]

Background: Salmonella enterica serotype Typhimurium produces surface-associated fimbriae that facilitate adherence of the bacteria to a variety of cells and tissues. Type 1 fimbriae with binding specificity to mannose residues are the most commonly found fimbrial type. In vitro, static-broth culture favors the growth of S. Typhimurium with type 1 fimbriae, whereas non-type 1 fimbriate bacteria are obtained by culture on solid-agar media. Previous studies demonstrated that the phenotypic expression of type 1 fimbriae is the result of the interaction and cooperation of the regulatory genes fimZ, fimY, fimW, and fimU within the fim gene cluster. Genome sequencing revealed a novel gene, stm0551, located between fimY and fimW that encodes an 11.4-kDa putative phosphodiesterase specific for the bacterial second messenger cyclic-diguanylate monophosphate (c-di-GMP). The role of stm0551 in the regulation of type 1 fimbriae in S. Typhimurium remains unclear. Results: A stm0551-deleted stain constructed by allelic exchange constitutively produced type 1 fimbriae in both static-broth and solid-agar medium conditions. Quantative RT-PCR revealed that expression of the fimbrial major subunit gene, fimA, and one of the regulatory genes, fimZ, were comparably increased in the stm0551-deleted strain compared with those of the parental strain when grown on the solid-agar medium, a condition that normally inhibits expression of type 1 fimbriae. Following transformation with a plasmid possessing the coding sequence of stm0551, expression of fimA and fimZ decreased in the stm0551 mutant strain in both culture conditions, whereas transformation with the control vector pACYC184 relieved this repression. A purified STM0551 protein exhibited a phosphodiesterase activity in vitro while a point mutation in the putative EAL domain, substituting glutamic acid (E) with alanine (A), of STM0551 or a FimY protein abolished this activity. Conclusions: The finding that the stm0551 gene plays a negative regulatory role in the regulation of type 1 fimbriae in S. Typhimurium has not been reported previously. The possibility that degradation of c-di-GMP is a key step in the regulation of type 1 fimbriae warrants further investigation. [ABSTRACT FROM AUTHOR]