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Platelets play a role in tumor angiogenesis and growth and are the main transporters of several angiogenesis regulators. Here, we aimed to determine the levels of angiogenesis regulators and epithelial-mesenchymal transition factors sequestered by circulating platelets in breast cancer patients and age-matched healthy controls. Platelet pellets (PP) and platelet-poor plasma (PPP) were collected by routine protocols. Vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), thrombospondin-1 (TSP-1), platelet factor 4 (PF4), and transforming growth factor-β1 (TGF-β1) were measured by enzyme-linked immunosorbent assay. Angiogenesis-associated expression of VEGF (2.1 pg/10(6) platelets versus 0.9 pg/10(6) platelets, P < 0.001), PF4 (21.2 ng/10(6) platelets versus 10.2 ng/10(6) platelets, P < 0.001), PDGF-BB (42.9 pg/10(6) platelets versus 19.1 pg/10(6) platelets, P < 0.001), and TGF-β1 (15.3 ng/10(6) platelets versus 4.3 ng/10(6) platelets, P < 0.001) differed in the PP samples of cancer and control subjects. In addition, protein concentrations were associated with clinical characteristics (P < 0.05). Circulating platelets in breast cancer sequester higher levels of PF4, VEGF, PDGF-BB, and TGF-β1, suggesting a possible target for early diagnosis. VEGF, PDGF, and TGF-β1 concentrations in platelets may be associated with prognosis.

Objective. The study aims to research the interventional effect and mechanism of astragaloside IV (Ast) synergizing with ferulic acid (FA) on idiopathic pulmonary fibrosis (IPF) induced by bleomycin in mice. Methods. The mice were randomly divided into seven groups with 10 mice in each group, namely, a sham operation group, a model group, a miRNA-29b (miR-29) group, a miR-29b negative control group (NC group), a FA group, an Ast group, and a combination group. A mouse model of pulmonary fibrosis was established by intratracheal instillation of bleomycin. Samples were collected after 28 days of continuous administration. Hematoxylin and eosin (HE) and Masson staining were used to observe pathological changes in the lung tissue, and the degree of fibrosis was evaluated using the hydroxyproline content. Changes in transforming growth factor-β1 (TGF-β1) and Smad3 in the lung were observed using immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) in the serum. PCR was used to detect the expression of the miR-29b, TGF-β1, Smad3, and nuclear factor E2-related factor 2 (Nrf2) genes. Western blotting was used to detect the content of the TGF-β/Smad3 protein. Results. Ferulic acid combined with astragaloside IV reduced the degree of pulmonary fibrosis and the synthesis of hydroxyproline in lung tissue. The combination of the two also regulated the oxidative stress response ， TGF-β1/Smad3 pathway and miR-29b in lung tissue. Conclusion. Astragaloside IV combined with ferulic acid regulated the oxidative stress of lung tissues and TGF-β1/Smad3 signaling through miR-29b, thereby reducing the degree of pulmonary fibrosis. This provides a reference direction for the clinical treatment of IPF patients. [ABSTRACT FROM AUTHOR]

Background. The prognosis of non-small-cell lung cancer (NSCLC) has not been significantly improved. In the past several years, research on epigenetics is in full swing. There is a focus on the gene EZH2; however, its role as a predictor of the prognosis of NSCLC is in the debate. Objective. To clarify if the expression level of EZH2 can influence the prognosis of NSCLC and explain its prognostic value. Methods. We have systematically searched PubMed, Web of Science, and Cochrane library, screened relevant articles, and conducted a meta-analysis on the expression level of EZH2 in NSCLC. We collected the hazard ratio (HR) and the 95% confidence interval (CI) and used STATA 12.0 to calculate the combined result of EZH2 overall survival. In addition, we conducted subgroup analyses, a sensitivity analysis, and a funnel plot to test the reliability of the results. We further validated these meta-analysis results using the Kaplan-Meier plotter database and The Cancer Genome Atlas (TCGA) database. In addition, we have investigated the correlation between EZH2 expression and EGFR expression, KRAS expression, BRAF expression, and smoking in TCGA database to further explore the mechanism behind the influence of high EZH2 expression on lung cancer prognosis. Results. 13 studies including 2180 participants were included in the meta-analysis. We found that high expression of EZH2 indicates a poor prognosis of NSCLC (HR = 1.65 and 95% CI 1.16-2.35; p ≤ 0.001). Subgroup analyses showed high heterogeneity in stages I-IV ( I 2 = 85.1 % and p ≤ 0.001) and stages I-III ( I 2 = 66.9 % and p = 0.029) but not in stage I ( I 2 = 0.00 % and p = 0.589). In the Kaplan-Meier plotter database, there was a high expression in 963 cases and low expression in 964 cases (HR = 1.31 and 95% CI 1.15-1.48; p < 0.05). Further analysis found that the high expression of EZH2 was statistically significant in lung adenocarcinoma (HR = 1.27 and 95% CI 1.01−1.6; p = 0.045), but not in lung squamous cell carcinoma (HR = 1.03 and 95% CI 0.81−1.3; p = 0.820). The results of the TCGA database showed that the expression of EZH2 in normal tissues was lower than that in lung cancer tissues (p < 0.05). Smoking was associated with high expression of EZH2 (p < 0.001). EZH2 was also highly expressed in lung cancers with positive KRAS expression, and the correlation was positive in lung adenocarcinoma (r = 0.3129 and p < 0.001). The correlation was also positive in lung squamous cell carcinoma (r = 0.3567 and p < 0.001). EZH2 expression was positively correlated with BRAF expression (r = 0.2397 and p < 0.001), especially in lung squamous cell carcinoma (r = 0.3662 and p < 0.001). In lung squamous cell carcinoma, a positive yet weak correlation was observed between EZH2 expression and EGFR expression (r = 0.1122 and p < 0.001). Conclusions. The high expression of EZH2 indicates a poor prognosis of NSCLC, which may be related to tumor stage or cancer type. EZH2 may be an independent prognostic factor for NSCLC. EZH2 high expression or its synergistic action with KRAS and BRAF mutations affects the prognosis of non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Fetal metabolic programming caused by the adverse intrauterine environment can induce metabolic syndrome in adult offspring. Adverse intrauterine environment introduces fetal long-term relatively irreversible changes in organs and metabolism, and thus causes fetal metabolic programming leading metabolic syndrome in adult offspring. Fetal metabolic programming of obesity and insulin resistance plays a key role in this process. The mechanism of fetal metabolic programming is still not very clear. It is suggested that epigenetic programming, also induced by the adverse intrauterine environment, is a critical underlying mechanism of fetal metabolic programming. Fetal epigenetic programming affects gene expression changes and cellular function through epigenetic modifications without DNA nucleotide sequence changes. Epigenetic modifications can be relatively stably retained and transmitted through mitosis and generations, and thereby induce the development of metabolic syndrome in adult offspring. This manuscript provides an overview of the critical role of epigenetic programming in fetal metabolic programming. [ABSTRACT FROM AUTHOR]

Pseudomonas syringae pv. syringae van Hall CFCC 1336 ( Pss 1336) is the causal agent of bacterial disease of stone fruit trees, and also able to elicit hypersensitive response (HR) in non-host tobacco. It is known that this pathogen uses PCS-pathway to synthesize phosphatidylcholine (PC), and mutation of the pcs gene abolishes bacterial PC synthesis. Previous study also found that the 1336 pcs − mutant lacking PC in its membrane phospholipids was unable to secrete HrpZ harpin and elicit HR in non-host plants. In this study, we further analyzed virulence of lipodepsipeptide phytoxins of Pss 1336 wild type ( pcs + ), the 1336RM ( pcs −/+) and the 1336 pcs − mutant, and found that the 1336 pcs− mutant was unable to cause necrosis of Chinese date fruits and inhibit fungal growth. HPLC analysis also showed that the 1336 pcs− mutant markedly reduced its secretion of lipodepsipeptide phytoxins. Analysis of semi-quantitative RT-PCR revealed that PC presence or absence did not affect gene expressions of SyrD, PseABC and PseEF efflux systems at transcriptional level. However, western blotting assays found that PseE and PseF present only in the cytoplasmic fractions but undetectable in the membrane extract of the 1336 pcs− mutant. PC absence obviously interrupted the translocation of two membrane-associated proteins PseE and PseF from cytoplasm to cell membranes to form an intact PseEF efflux system in bacterial membranes. Failure to form PseEF efflux system could be a major factor for less lipopeptide-phytoxin secretion. Our results demonstrate that PC in bacterial membrane phospholipids plays an important role in maintaining physiological functions of PseEF efflux system. [ABSTRACT FROM AUTHOR]

Steroid-associated osteonecrosis of the femoral head remains a challenging problem in orthopedics worldwide. One pathomechanism is ischemia of the femoral head, as a result of thrombus formation and vasoconstriction. The present study investigates the effects of combination prevention with enoxaparin and EGb 761 on steroid-associated ONFH in rabbits. Rabbits were randomly divided into 5 groups (control group, model group, enoxaparin group, ginkgo group, and combination group). With the exception of the control group, the groups of rabbits were modeled with lipopolysaccharide and methylprednisolone acetate. Starting with modeling, the enoxaparin group and ginkgo group were injected with 1 μg/kg/day enoxaparin subcutaneously and orally given 40 mg/kg/day EGb 761 for 4 weeks, respectively; the combination group received both treatments. After modeling for 6 weeks, the hematology data indicated prolonged PT and APTT in the three prevention groups. The micro-CT examination revealed higher bone density and better structure; histomorphometry revealed significant pathological changes. Immunohistochemistry revealed higher expression of BMP-2 and VEGF, thus revealing better osteogenesis and angiogenesis activities. Among the three prevention groups, the combination group had the most efficient results. In conclusion, the combined prevention with an anticoagulant and a vasodilator has the potential to decrease the incidence of steroid-associated ONFH in rabbits. [ABSTRACT FROM AUTHOR]

The scavenger receptor class B, type I (SR-BI), is a member of the CD36 superfamily comprising transmembrane proteins involved in mammalian and fish lipid homeostasis regulation. We hypothesize that this receptor plays an important role in Macrobrachium nipponense lipid metabolism. However, little attention has been paid to SR-BI in commercial crustaceans. In the present study, we report a cDNA encoding M. nipponense scavenger receptor class B, type I (designated as MnSR-BI), obtained from a hepatopancreas cDNA library. The complete MnSR-BI coding sequence was 1545 bp, encoding 514 amino acid peptides. The MnSR-BI primary structure consisted of a CD36 domain that contained two transmembrane regions at the N- and C-terminals of the protein. SR-BI mRNA expression was specifically detected in muscle, gill, ovum, intestine, hepatopancreas, stomach, and ovary tissues. Furthermore, its expression in the hepatopancreas was regulated by dietary lipid sources, with prawns fed soybean and linseed oils exhibiting higher expression levels. RNAi-based SR-BI silencing resulted in the suppression of its expression in the hepatopancreas and variation in the expression of lipid metabolism-related genes. This is the first report of SR-BI in freshwater prawns and provides the basis for further studies on SR-BI in crustaceans. [ABSTRACT FROM AUTHOR]

Objective: There is a heated debate on whether the prognostic value of NME1 is favorable or unfavorable. Thus, we carried out a meta-analysis to evaluate the relationship between NME1 expression and the prognosis of patients with digestive system neoplasms. Methods: We searched PubMed, EMBASE and Web of Science for relevant articles. The pooled odd ratios (ORs) and corresponding 95%CI were calculated to evaluate the prognostic value of NME1 expression in patients with digestive system neoplasms, and the association between NME1 expression and clinicopathological factors. We also performed subgroup analyses to find out the source of heterogeneity. Results: 2904 patients were pooled from 28 available studies in total. Neither the incorporative OR combined by 17 studies with overall survival (OR = 0.65, 95%CI:0.41–1.03, P = 0.07) nor the pooled OR with disease-free survival (OR = 0.75, 95%CI:0.17–3.36, P = 0.71) in statistics showed any significance. Although we couldn’t find any significance in TNM stage (OR = 0.78, 95%CI:0.44–1.36, P = 0.38), elevated NME1 expression was related to well tumor differentiation (OR = 0.59, 95%CI:0.47–0.73, P<0.00001), negative N status (OR = 0.54, 95%CI:0.36–0.82, P = 0.003) and Dukes’ stage (OR = 0.43, 95%CI:0.24–0.77, P = 0.004). And in the subgroup analyses, we only find the “years” which might be the source of heterogeneity of overall survival in gastric cancer. Conclusions: The results showed that statistically significant association was found between NME1 expression and the tumor differentiation, N status and Dukes’ stage of patients with digestive system cancers, while no significance was found in overall survival, disease-free survival and TNM stage. More and further researches should be conducted to reveal the prognostic value of NME1. [ABSTRACT FROM AUTHOR]

Direct seeding is considered an efficient cultivation technology that reduces water use and labor costs. Mesocotyl length is one of the significant traits in cultivation; long mesocotyl is beneficial for the rate and uniformity of seedling emergence. In this study, we used a core collection of 137 rice accessions to identify quantitative trait loci (QTL) for mesocotyl elongation. A genome-wide association study (GWAS), combined with a principal component analysis (PCA) and a kinship matrix analysis, was conducted for the genotype analysis of 2 million, high-quality single nucleotide polymorphisms (SNPs). Through this GWAS analysis, 11 lead SNPs were confirmed to be associated with mesocotyl length, and a linkage disequilibrium (LD) decay analysis identified the 230 kb exploratory range for the detection of QTLs and candidate genes. Based on the gene expression database and haplotype analysis, five candidate genes (Os01g0269800, Os01g0731100, Os08g0136700, Os08g0137800, and Os08g0137900) were detected to be significantly associated with phenotypic variation. Five candidate gene expressions are reported to be associated with various plant hormone responses. Interestingly, two biotic stress response genes and two copper-containing redox proteins were detected as the candidate genes. The results of this study provide associated SNPs in candidate genes for mesocotyl length and strategies for developing direct seeding in breeding programs. [ABSTRACT FROM AUTHOR]

Background: SNAT1 is a subtype of the amino acid transport system A that has been implicated to play a potential role in cancer development and progression, yet its role in breast cancer remains unclear. In present study, we detected SNAT1 expression in breast cancers and explored its underlying mechanism in promoting breast carcinogenesis.Methods: RT-PCR and Western blotting were performed to analyze the transcription and protein levels of SNAT1 in breast cancer cell lines and fresh tissues. Tissue microarray blocks containing breast cancer specimens obtained from 210 patients were constructed. Expression of SNAT1 in these specimens was analyzed using immunohistochemical studies. SNAT1 was down-regulated by SNAT1-shRNA in breast cancer cells and the functional significance was measured.Results: SNAT1 was up-regulated in breast cancer cell lines and breast cancer tissues. Overexpression of SNAT1 was observed in 127 cases (60.5%). Expression of SNAT1 was significantly associated with tumor size, nodal metastasis, advanced disease stage, Ki-67, and ER status. Suppression of endogenous SNAT1 leads to cell growth inhibition, cell cycle arrest, and apoptosis of 4T1 cells and lowered the phosphorylation level of Akt. SNAT1 expression correlated significantly with p-Akt expression in human breast cancer samples.Conclusions: The cross-talk between Akt signaling and SNAT1 might play a critical role in the development and progression of breast cancer, providing an important molecular basis for novel diagnostic markers and new attractive targets in the treatment of breast cancer patients. [ABSTRACT FROM AUTHOR]

Salinity is one of the major constraints causing soil problems and is considered a limitation to increased rice production in rice-growing countries. This genome-wide association study (GWAS) experiment was conducted to understand the genetic basis of salt tolerance at the seedling stage in Korean rice. After 10 days of salt stress treatment, salt tolerance was evaluated with a standard evaluation system using a visual salt injury score. With 191 Korean landrace accessions and their genotypes, including 266,040 single-nucleotide polymorphisms (SNPs), using a KNU Axiom Oryza 580K Genotyping Array, GWAS was conducted to detect three QTLs with significant SNPs with a −log10(P) threshold of ≥3.66. The QTL of qSIS2, showed −log10(P) = 3.80 and the lead SNP explained 7.87% of total phenotypic variation. The QTL of qSIS4, showed −log10(P) = 4.05 and the lead SNP explained 10.53% of total phenotypic variation. The QTL of qSIS8 showed −log10(P) = 3.78 and the lead SNP explained 7.83% of total phenotypic variation. Among the annotated genes located in these three QTL regions, five genes were selected as candidates (Os04g0481600, Os04g0485300, Os04g0493000, Os04g0493300, and Os08g0390200) for salt tolerance in rice seedlings based on the gene expression database and their previously known functions. [ABSTRACT FROM AUTHOR]

Abstract: The ability of dimorphic transition between yeast and hyphal forms in Candida albicans is one of the vital determinants for its pathogenicity and virulence. We isolated C. albicans SWI1 as a suppressor of the invasive growth defect in a Saccharomyces cerevisiae mutant. Expression of C. albicans SWI1 in S. cerevisiae partially complemented the growth defect of a swi1 mutant in the utilization of glycerol. Swi1 is in a complex with Snf2 in C. albicans, and both proteins are localized in the nucleus independent of the growth form. Deleting SWI1 or SNF2 in C. albicans prevented true hyphal formation and resulted in constitutive pseudohypha-like growth in all media examined. Furthermore, swi1/swi1 mutant was defective in hypha-specific gene expression and avirulent in a mouse model of systemic infection. These data strongly suggest the conserved Swi/Snf complex in C. albicans is required for hyphal development and pathogenicity. [Copyright &y& Elsevier]

Background and objective The present study aims to detect the altered lncRNA expression in the mouse cortex after traumatic brain injury (TBI). We also simultaneously detected the altered mRNA profile to further analyze the possible function of lncRNA. Method C57BL/6 mice (n=18) were used to construct a controlled cortical impact model. At 24 h post-TBI, the cortex around injury site was collected and the total RNA was extracted to construct the cDNA library. RNA sequencing (RNA-seq) was carried out followed by RT-PCR for confirmation. Bioinformatic analysis (including GO analysis, KEGG pathway and co-expression analysis) also were performed. Results A total of 64,530 transcripts were detected in the current sequencing study, in which 27,457 transcripts were identified as mRNA and 37,073 transcripts as lncRNA. A total of 1580 mRNAs (1430 up-regulated and 150 down-regulated) and 823 lncRNAs (667 up-regulated and 156 down-regulated) were significantly changed according to the criteria ( | log 2 (fold change) |>1 and P <0.05). These altered mRNAs were mainly related to inflammatory and immunological activity, metabolism, neuronal and vascular network. The expression of single lncRNA may be related with several mRNAs, and so was the mRNA. Also, a total of 360 new mRNAs and 8041 new lncRNAs were identified. The good reproducibility and reliability of RNA-seq were confirmed by RT-PCR. Conclusion Numerous lncRNAs and mRNAs were significantly altered in mouse cortex around the injury site 24 h after TBI. Our present data may provide a promising approach for further study about TBI. [ABSTRACT FROM AUTHOR]