Crenobacter oryzisoli sp. nov., a novel phosphate-solubilizing bacterium isolated from the paddy soil.

Two Gram-staining-negative, facultative anaerobic, rod-shaped and phosphate-solubilizing strains designated SG2303T and SG2305, were isolated from paddy soil in China. Phylogenetic analysis based on 16 S rRNA gene sequences indicated that SG2303T and SG2305 represented a member of the genus Crenobacter within the family Neisseriaceae of the phylum Pseudomonadota. Strain SG2303T displayed higher 16 S rRNA gene sequence similarities with members of the genus Crenobacter ranging from 93.5 to 94.0%. Strains C. luteus YIM 78141T and C. cavernae K1W11S-77T were closest related to the isolated strains and were considered as type strains. Growth of strain SG2303T occurred at 10-55 °C (optimum 37 °C), pH 5.0-9.0 (optimum pH 6.0-7.0) and 0-1% (w/v) NaCl (optimum 0%). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain SG2303T and its closely related taxa were 76.1-78.2% and 20.5-22.1%, respectively. The genomic DNA G + C content was 62.2%. The quinone of strain SG2303T was Q-8. The major fatty acids (> 10%) of strain SG2303T were C16:0 (30.6%), summed feature 3 (C16:1ω7c and/or C16:1ω6c) (26.0%) and C12:0 3OH (12.1%). The polar lipids were phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phospholipids (PL), glycolipid (GL) and unidentified lipids (UL). Based on the results of the phylogenetic, physiological, biochemical, and morphological analysis, strain SG2303T is recognized as a novel species of the genus Crenobacter, for which the name Crenobacter oryzisoli sp. nov. is proposed. The type strain is SG2303T (= GDMCC 1.3970T = JCM 36468T). In addition, SG2303T was also able of phosphorus solubilization and promoting the growth of rice seeds. Strain SG2303T exhibited a relatively high dissolvable phosphorus content of 2.52 µg·mL- 1.

Genome-wide DNA methylation analysis identifies potent CpG signature for temzolomide response in non-G-CIMP glioblastomas with unmethylated MGMT promoter: MGMT-dependent roles of GPR81.

PURPOSES: To identify potent DNA methylation candidates that could predict response to temozolomide (TMZ) in glioblastomas (GBMs) that do not have glioma-CpGs island methylator phenotype (G-CIMP) but have an unmethylated promoter of O-6-methylguanine-DNA methyltransferase (unMGMT). METHODS: The discovery-validation approach was planned incorporating a series of G-CIMP-/unMGMT GBM cohorts with DNA methylation microarray data and clinical information, to construct multi-CpG prediction models. Different bioinformatic and experimental analyses were performed for biological exploration. RESULTS: By analyzing discovery sets with radiotherapy (RT) plus TMZ versus RT alone, we identified a panel of 64 TMZ efficacy-related CpGs, from which a 10-CpG risk signature was further constructed. Both the 64-CpG panel and the 10-CpG risk signature were validated showing significant correlations with overall survival of G-CIMP-/unMGMT GBMs when treated with RT/TMZ, rather than RT alone. The 10-CpG risk signature was further observed for aiding TMZ choice by distinguishing differential outcomes to RT/TMZ versus RT within each risk subgroup. Functional studies on GPR81, the gene harboring one of the 10 CpGs, indicated its distinct impacts on TMZ resistance in GBM cells, which may be dependent on the status of MGMT expression. CONCLUSIONS: The 64 TMZ efficacy-related CpGs and in particular the 10-CpG risk signature may serve as promising predictive biomarker candidates for guiding optimal usage of TMZ in G-CIMP-/unMGMT GBMs.

A ROS/Akt/NF-κB Signaling Cascade Mediates Epidermal Growth Factor-Induced Epithelial-Mesenchymal Transition and Invasion in Human Breast Cancer Cells.

Background: As one of the most widely used anti-diabetic drugs for type II diabetes, metformin has been shown to exhibit anti-cancer activity in recent years. Epidermal growth factor (EGF) and its receptor, EGFR, play important roles in cancer metastasis in various tumors, including breast cancer. Epithelial-mesenchymal transition (EMT) is a critical process for cancer invasion and metastasis. In this study, we use EGF as a metastatic inducer to investigate the effect of metformin on cancer cell migration, invasion and EMT. Methods: Human breast cancer MCF-7 cells were exposed to EGF with or without metformin or N-acetyl cysteine (NAC). The effects of metformin on breast cancer cell proliferation were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The production of reactive oxygen species (ROS) was tested using 2,7-dichlorodihydrofluorecein diacetate (DCFH-DA). The migratory and invasive abilities of tumor cells were analyzed using wound healing assay and transwell invasion assay, respectively. The expressions of E-cadherin, N-cadherin and Snail were tested using real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting at mRNA and protein levels. The activation of protein kinase B (Akt) and nuclear factor kappa B (NF-κB) were measured by western blotting. Results: Our results showed that metformin inhibited breast cancer cell proliferation in a dose-dependent manner with or without EGF. EGF-induced alterations in cell morphology that are characteristic of EMT were reversed by metformin. Metformin also inhibited the EGF-modulated expression of E-cadherin, N-cadherin and Snail and further suppressed cell invasion and migration. In addition, metformin suppressed EGF-induced phosphorylation of Akt and NF-κB. ROS is involved in EGF-induced cancer invasion and activation of phosphatidylinositol 3-kinase (PI3K)/Akt/NF-κB pathway. Conclusion: Taken together, these data indicate that metformin suppresses EGF-induced breast cancer cell migration, invasion and EMT through the inhibition of the PI3K/Akt/NF-κB pathway. These results provide a novel mechanism to explain the role of metformin as a potent anti-metastatic agent in breast cancer cells.

Spleen contributes to restraint stress induced hepatocellular carcinoma progression.

The spleen is the largest secondary immune organ and plays a critical role in the progression of tumor. Psychological stress promotes tumor progression through inhibiting antitumor immune. However, the role of spleen in tumor progression induced by stress is unclear. Here, we showed that restraint stress promoted tumor growth, increased the percentage of CD11b+Gr-1+ MDSC while decreased the percentages of CD3-NK1.1+ NK and CD3+NK1.1+ NKT in the tumor tissues. Restraint stress decreased the percentages of CD3+CD4+ T lymphocytes and CD3+CD8+ T lymphocytes while increased the percentage of CD11b+Gr-1+ MDSC in the blood of tumor-bearing mice. Restraint stress increased the percentages of CD3+CD4+ T lymphocytes, CD3+CD8+ T lymphocytes, CD4+PD1+ T lymphocytes and CD8+PD1+ T lymphocytes while decreased the percentage of CD11b+Gr-1+ MDSC in the spleen of tumor-bearing mice. Interestingly, splenectomy inhibited tumor growth and attenuated the changes of CD3+CD4+ T lymphocytes, CD3+CD8+ T lymphocytes, and CD11b+Gr-1+ MDSC in blood induced by chronic restraint stress. Finally, splenectomy blocked the increases of CD11b+Gr-1+ MDSC but did not attenuate the decreases of CD3-NK1.1+ NK and CD3+NK1.1+ NKT in tumor tissue induced by chronic stress. Together, these data indicate that chronic restraint stress promotes hepatocellular carcinoma growth and suppresses the antitumor immunity of tumor-bearing mice. Splenectomy could inhibit tumor growth and partly block the decrease of antitumor immune activity induced by stress.

Psychological effects of project-based learning in participants receiving clinical oncology teaching: A protocol of systematic review of randomized controlled trials.

BACKGROUND: This study will assess the effects of the project-based learning (PBL) for participants undergoing clinical oncology teaching (COT). METHODS: A systematic and comprehensive literature records will be identified from the electronic databases of PUBMED, EMBASE, Cochrane Library, Web of Science, Springer, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All electronic databases will be searched from their inceptions up to the present. Any relevant randomized controlled trials on the effects of PBL in participants receiving COT will be considered for inclusion. Study quality will be assessed using the Cochrane risk of bias tool. RevMan 5.3 software will be utilized for statistical analysis. RESULTS: This study will assess the effects of PBL in participants receiving COT through assessing the primary outcomes of psychological disorders, student satisfaction, and student feedback, and secondary outcomes of examination scores, excellence rates, course examination pass rates, and clinical knowledge or skills. CONCLUSION: The findings of this study will summarize the latest evidence on the effects of PBL in participants receiving in COT. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019150433.

Virtual Screening for Type II B Inhibitors of B-RafV600E Kinase.

BACKGROUND: B-RafV600E kinase was identified as an important target in current cancer treatment, and the type II B inhibitors show good qualities in preclinical studies. Therefore, it is very important to discover novel II B inhibitors of B-RafV600E kinase. METHODS: In order to discover novel II B inhibitors of B-RafV600E kinase, virtual screening against ZINC database was performed by using a combination of pharmacophore modelling, molecular docking, 3DQSAR model and binding free energy (ΔGbind) calculation studies. The inhibitory activities against A375 cell lines of the hit compounds were tested by using MTT assay. RESULTS: Five promising hit compounds were obtained after screening, and all the five hit compounds showed good inhibitory rates against A375 cell lines. CONCLUSION: The combined approach of the virtual screening in our work is effective, which can be used to discover novel inhibitors with a new skeleton. In addition, the five compounds obtained from the screening showed good inhibitory rates against A375 cell lines, which can be considered to develop new II B inhibitors of B-RafV600E kinase.

miR-650 Promotes the Metastasis and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma by Directly Inhibiting LATS2 Expression.

BACKGROUND/AIMS: Previous studies have confirmed that microRNAs are involved in the metastasis and epithelial-mesenchymal transition (EMT) of malignancies. In this study, we examined whether miR-650 promotes the migration, invasion, and EMT of hepatocellular carcinoma (HCC) cells by targeting the large tumor suppressor kinase 2 gene (LATS2). METHODS: qRT-PCR was used to detect expression of miR-650 in HCC tissues and paired normal tissues. MTT and Transwell assay were used to observe the effect of miR-650 on proliferation, migration and invasion of HCC cells. Western blot assay and Immunohistochemistry were performed to demonstrate association between miR-650 expression level and epithelial-mesenchymal transition (EMT) related protein. Mechanistically, Reporter luciferase assay was performed to reveal whether large tumor suppressor kinase 2 (LATS2) was a direct target of miR-650 in HCC cells. RESULTS: We observed that miR-650 levels were largely up-regulated in HCC tissues, and that the increased expression was closely associated with the adverse clinical features of HCC patients. Additionally, the expression of LATS2, which was identified as a direct target of miR-650, can counteract the effects of miR-650 in HCC. Furthermore, we demonstrated that high miR-650 expression levels and low LATS2 expression levels in tumors may indicate a poor prognosis for HCC patients. CONCLUSION: In conclusion, the miR-650/LATS2 pathway may serve as a novel prognostic biomarker and an attractive therapeutic target for HCC patients.

miR-103 promotes the metastasis and EMT of hepatocellular carcinoma by directly inhibiting LATS2.

Improving the long­term survival of patients with hepatocellular carcinoma (HCC) remains a challenge due to metastasis and recurrence. In this study, we demonstrate that the overexpression of miR­103 in HCC cells promotes epithelial­mesenchymal transition (EMT), and is associated with an enhanced metastasis and poor outcomes, as shown by western blot analysis and immunohistochemistry. Mechanistically, using reporter luciferase assay we reveal that the serine/threonine­protein kinase, large tumor suppressor kinase 2 (LATS2), a key component of the Hippo signaling pathway, is a direct target of miR­103 in HCC cells. Transwell assay, MTT assay and western blot analysis were performed to reveal that LATS2 can counteract the functional effects of miR­103 on HCC metastasis, growth and EMT. The analyses of clinical data indicated that a high expression of miR­103 correlated with a high expression of vimentin, but with a low expression of LATS2 and E­cadherin in HCC tissues. miR­103 also reduced yes­associated protein (YAP) phosphorylation. On the whole, the findings of this study suggest that miR­103 promotes HCC metastasis and EMT by directly inhibiting LATS2. Thus, targeting miR­103/LATS2 may prove to be a promising therapeutic strategy for HCC.

Virtual screening of B-Raf kinase inhibitors: A combination of pharmacophore modelling, molecular docking, 3D-QSAR model and binding free energy calculation studies.

B-Raf kinase has been identified as an important target in recent cancer treatment. In order to discover structurally diverse and novel B-Raf inhibitors (BRIs), a virtual screening of BRIs against ZINC database was performed by using a combination of pharmacophore modelling, molecular docking, 3D-QSAR model and binding free energy (ΔGbind) calculation studies in this work. After the virtual screening, six promising hit compounds were obtained, which were then tested for inhibitory activities of A375 cell lines. In the result, five hit compounds show good biological activities (IC50<50µM). The present method of virtual screening can be applied to find structurally diverse inhibitors, and the obtained five structurally diverse compounds are expected to develop novel BRIs.

Genetic polymorphisms (rs10636 and rs28366003) in metallothionein 2A increase breast cancer risk in Chinese Han population.

Genetic polymorphisms of MT2A are frequently observed in many different cancers. We performed this case-control study, including 459 breast cancer (BC) patients and 549 healthy controls from Northwest China, to evaluate the associations between two common MT2A polymorphisms (rs10636 and rs28366003) and BC risk. The MT2A polymorphisms were genotyped via Sequenom MassARRAY. The individuals with the rs28366003 A/G, A/G-G/G genotypes underwent a higher risk of BC (P<0.0001). And, the minor allele G of rs28366003 was related to an increased BC risk (P<0.0001). We also found a significantly increased BC risk with rs10636 polymorphism among homozygote and recessive models (P<0.05). Further subgroup analysis by clinical characteristics of BC patients showed that Scarff, Bloom and Richardson tumor grade (SBR) 1-2 have a higher expression of the minor allele of these two MT2A loci than SBR 3. Our results indicated that the rs10636 and rs28366003 polymorphisms in MT2A increased BC risk in Northwest Chinese Han population.

Latest research progress in the correlation between baicalein and breast cancer invasion and metastasis.

Breast cancer is one of the most commonly occurring female malignant tumors. According to the 2012 GLOBOCAN statistics, produced by the International Agency for Research On Cancer ('IARC'), nearly 1.7 million women were diagnosed with breast cancer, with 522,000 related deaths: An increase in the incidence of breast cancer and associated mortality by nearly 18% from 2008. Metastasis is the final step in breast cancer progression, and represents the most common cause of mortality in patients with breast cancer. Therefore, a search for low-toxicity, safe and effective anti-breast cancer drugs in the form of natural compounds has become an intense focus of research. Baicalein, a widely used Chinese herbal medicine, has extensive antitumor activity. The present review briefly describes the research that has been performed on the association between baicalein and breast cancer metastasis, and further illustrates the influence of baicalein on the underlying mechanisms of breast cancer metastasis, adding a novel theory basis for baicalein antitumor research. In conclusion, baicalein may represent a promising target for the prevention and therapy of breast cancer.

The Associations of Single Nucleotide Polymorphisms in miR196a2, miR-499, and miR-608 With Breast Cancer Susceptibility: A STROBE-Compliant Observational Study.

MicroRNAs (miRNAs) play an important role as regulators of tumor suppressors and oncogenes in cancer-related processes. Single nucleotide polymorphisms (SNPs) in miRNAs have been shown to be relevant to various different cancers, including breast cancer (BC). The aim of this study was to estimate the associations between miRNA-related gene polymorphisms (miR-196a2, miR-499, and miR-608) and the risk of BC in a Chinese population. Gene polymorphisms were analyzed in 1143 subjects (controls = 583; BC = 560). The 3 SNPs were genotyped using the Sequenom Mass-ARRAY platform. The associations between the SNP frequencies and BC were assessed by computing odds ratios (ORs) and 95% confidence intervals (95% CIs), as well as by applying Chi-square tests. The miR-196a2 (rs11614913) T allele was associated with a decreased risk of BC based on results from dominant (OR = 0.67, 95% CI = 0.52-0.86), recessive (OR = 0.65, 95% CI = 0.48-0.86), and allele models (OR = 0.73, 95% CI = 0.62-0.86). In contrast, the miR-499 (rs3746444) AG/GG genotypes were associated with an increased risk of BC (OR = 1.45, 95% CI = 1.10-1.91), and miR-608 (rs4919510) was not significantly associated with BC risk. Our study suggested that the polymorphisms of rs11614913 and rs3746444 may be associated with BC risk in Chinese individuals.

Genetic Variation in Metastasis-Associated in Colon Cancer-1 and the Risk of Breast Cancer Among the Chinese Han Population: A STROBE-Compliant Observational Study.

Metastasis-associated in colon cancer-1 (MACC1), a newly identified oncogene, is involved in angiogenesis, invasiveness, and metastasis in many cancers. Epidemiological studies have indicated the associations between MACC1 polymorphisms and cancer risk. However, the association between genetic polymorphisms in MACC1 and breast cancer (BC) was not clear. This study aimed to evaluate the relationship between MACC1 polymorphisms and BC risk.We genotyped 4 single-nucleotide polymorphisms (SNPs) in MACC1 (rs975263, rs1990172, rs3735615, rs4721888) to determine the haplotypes in 560 BC patients and 583 age-, sex-, and ethnicity-matched healthy individuals. Genotypes were determined using the Sequenom MassARRAY method. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) using the chi-square test.There were significant differences between patients and controls in the MACC1 rs975263 allelic (T vs C: OR = 0.76, 95% CI = 0.61-0.95, P = 0.014) and genotypic groups (TC vs TT: OR = 0.70, 95% CI = 0.54-0.92, P = 0.009; TC+CC vs TT: OR = 0.71, 95% CI = 0.55-0.92, P = 0.008). Analysis of clinical features demonstrated significant associations between rs975263 and Scarff-Bloom-Richardson (SBR) grade 3 cancer (P = 0.006) and postmenopausal women (P = 0.018). Compared with the rs4721888 CC genotype, the frequency of rs4721888 GC and GC+CC variants was higher in patients. Further analysis revealed that the variant genotypes were positively associated with lymph node metastasis. However, we failed to find any relationships between rs1990172 or rs3735615 polymorphism and BC risk. In addition, haplotype analysis indicated that the CTGG and CTCG haplotypes (rs975263, rs1990172, rs3735615, rs4721888) were significantly associated with decreased susceptibility to BC (P = 0.029 and 0.019 respectively).Our results suggest that rs975263 and rs4721888 polymorphisms in MACC1 are associated with the risk of BC susceptibility and may be involved in the progression of BC in Chinese women.

Effect of baicalein on the expression of SATB1 in human breast cancer cells.

The aim of the present study was to investigate the effects of baicalein on the protein expression of SATB1 in the MDA-MB-231 human breast cancer cell line. MDA-MB-231 cells were treated with various concentrations of baicalein (0, 10, 20, 40 µM). Following treatment, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and wound healing assay were used to detect the changes in cell proliferation and migration. In addition, western blot analysis was performed to detect the changes in the protein expression levels of SATB1 in the MDA-MB-231 cell line. With the prolongation of administration time and the increase in drug concentration, the inhibitory effect of baicalein on the proliferation and migration of MDA-MB-231 cells gradually increased in a time- and dose-dependent manner (P<0.05). In addition, baicalein was shown to markedly decrease the protein expression levels of SATB1 in the MDA-MB-231 cells. With increasing drug concentrations, the protein expression levels of SATB1 decreased gradually (P<0.05). Therefore, baicalein was demonstrated to inhibit the proliferation of MDA-MB-231 cells and downregulate the protein expression of SATB1, indicating that baicalein can significantly inhibit the proliferation, migration and invasiveness of MDA-MB-231 cells by downregulating the expression of SATB1.

WRKY41 controls Arabidopsis seed dormancy via direct regulation of ABI3 transcript levels not downstream of ABA.

Although seed dormancy is an important agronomic trait, its molecular basis is poorly understood. ABSCISIC ACID INSENSITIVE 3 (ABI3) plays an essential role in the establishment of seed dormancy. Here, we show that the lack of a seed-expressed WRKY transcription factor, WRKY41, confers reduced primary seed dormancy and thermoinhibition, phenotypes resembling those for a lack of ABI3. Loss-of-function abi3-17 and wrky41 alleles also both confer reduced sensitivity to ABA during germination and early seedling growth. Absence of WRKY41 decreases ABI3 transcript abundance in maturing and imbibed seeds, whereas transgenically overexpressing WRKY41 increases ABI3 expression. Moreover, transgenic overexpression of ABI3 completely restores seed dormancy phenotypes on wrky41. ChIP-qPCR and EMSA reveal that WRKY41 binds directly to the ABI3 promoter through three adjacent W-boxes, and a transactivation assay indicates that these W-boxes are essential for ABI3 expression. Whilst RT-qPCR analysis shows that the regulation of ABI3 by WRKY41 is not through ABA and other factors known to promote ABI3 transcription during seed maturation and germination, we also show that high concentrations of ABA might promote negative feedback regulation of WRKY41 expression. Finally, analysis of the wrky41 aba2 double mutant confirms that WRKY41 and ABA collaboratively regulate ABI3 expression and seed dormancy. In summary, our results demonstrate that WRKY41 is an important regulator of ABI3 expression, and hence of seed dormancy.

Functional promoter -765 G > C variant in COX-2 gene is associated with the susceptibility of breast cancer in Chinese Han women.

BACKGROUND: Cyclooxygenase (COX) is a rate-limiting enzyme in prostaglandins synthesis which exists in two isoforms, COX-1 and COX-2. Over-expression of COX-2 was considered to increase the proliferation and enhance the invasiveness of breast cancer cells. It was suggested that genetic variations in COX-2 could influence its expression. Herein, the present study was aimed to investigate the associations between two mostly studied functional polymorphisms (-765 G > C and 8473 C > T) in COX-2 and breast cancer risk in Chinese Han women. METHODS: In the hospital-based case-control study, 465 breast cancer patients and 799 cancer-free controls were genotyped for the COX-2 -765 G > C and 8473 C > T polymorphisms using TaqMan assay. We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using the logistic regression. RESULTS: Compared with the wild genotype of -765 G > C, we found a statistically significant increased risk of breast cancer associated with the variant genotypes [GC/CC vs. GG: OR = 1.56, 95% CI = 1.11-2.21]. In the stratified analysis, the increased risk was more predominant among the subgroups of younger subjects (OR = 1.61, 95% CI = 1.00-2.61). Furthermore, the variant genotypes were associated with large tumor size (OR = 3.01, 95% CI = 1.47-6.12). No significant association was observed for the 8473 C > T polymorphism. CONCLUSIONS: Our results suggest that the functional -765 G > C polymorphism in the promoter of COX-2 may influence the susceptibility and progression of breast cancer in the Chinese Han population.

Association between MDM2 rs 2279744 polymorphism and breast cancer susceptibility: a meta-analysis based on 9,788 cases and 11,195 controls.

PURPOSE: Previous studies have suggested associations between MDM2 (mouse double minute 2 homolog) polymorphisms and cancer risk. The aim of this study was to evaluate the relationship between the MDM2 rs 2279744 polymorphism and the susceptibility of breast cancer. METHODS: We searched PubMed, Web of Knowledge, Embase, and the Chinese National Knowledge Infrastructure (CNKI) database for case-control studies published up to October 2013 that investigated MDM2 rs 2279744 polymorphism and breast cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of these associations. RESULTS: A total of 19 studies were identified for the meta-analysis, including 9,788 cases and 11,195 controls. The variant heterozygote (TG) was associated with breast cancer risk in the overall population (TG vs TT: OR =1.10, 95% CI =1.04-1.17, P=0.001, P=0.23 for heterogeneity test). In the subgroup analyses by ethnicity, a significantly increased risk was observed among Asians (G vs T: OR =1.12, 95% CI =1.02-1.23, P=0.02, P het=0.04; GG vs TT: OR =1.29, 95% CI =1.06-1.56, P=0.01, P het=0.04; TG vs TT: OR =1.36, 95% CI =1.15-1.60, P=0.0004, P het=0.45; dominant model TG+GG vs TT: OR =1.21, 95% CI =1.03-1.41, P=0.02, P het=0.07). However, among Caucasians, rs 2279744 was associated with breast cancer risk in only one genotype (TG vs TT: OR =1.09, 95% CI =1.00-1.18, P=0.04, P het=0.37). No publication bias was found in the present study. CONCLUSION: This meta-analysis provides evidence for the association between the MDM2 rs 2279744 polymorphism and breast cancer susceptibility. The results suggest that the MDM2 rs 2279744 polymorphism plays an important role in breast cancer, especially in Asians.

Transcription factor WRKY46 regulates osmotic stress responses and stomatal movement independently in Arabidopsis.

Drought and salt stress severely inhibit plant growth and development; however, the regulatory mechanisms of plants in response to these stresses are not fully understood. Here we report that the expression of a WRKY transcription factor WRKY46 is rapidly induced by drought, salt and oxidative stresses. T-DNA insertion of WRKY46 leads to more sensitivity to drought and salt stress, whereas overexpression of WRKY46 (OV46) results in hypersensitivity in soil-grown plants, with a higher water loss rate, but with increased tolerance on the sealed agar plates. Stomatal closing in the OV46 line is insensitive to ABA because of a reduced accumulation of reactive oxygen species (ROS) in the guard cells. We further find that WRKY46 is expressed in guard cells, where its expression is not affected by dehydration, and is involved in light-dependent stomatal opening. Microarray analysis reveals that WRKY46 regulates a set of genes involved in cellular osmoprotection and redox homeostasis under dehydration stress, which is confirmed by ROS and malondialdehyde (MDA) levels in stressed seedlings. Moreover, WRKY46 modulates light-dependent starch metabolism in guard cells via regulating QUA-QUINE STARCH (QQS) gene expression. Taken together, we demonstrate that WRKY46 plays dual roles in regulating plant responses to drought and salt stress and light-dependent stomatal opening in guard cells.

Anti-angiogenic effect of the total flavonoids in Scutellaria barbata D. Don.

BACKGROUND: Angiogenesis is closely related to the growth, invasion and metastasis of tumors, also considered as the key target of anticancer therapy. Scutellaria barbata D. Don (S. barbata), a traditional Chinese medicine, is being used to treat various diseases, including cancer. However, the antitumor molecular mechanism of S. barbata was still unclear. This study aimed to investigate the inhibitory effects of the total flavones in S. barbata (TF-SB) on angiogenesis. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with various concentrations of TF-SB. Cell viability was examined using the MTT assay. The scratch assay was used to detect the migration of HUVECs after treatment with TF-SB. The ability of HUVECs to form network structures in vitro was demonstrated using the tube formation assay. The chick embryo chorioallantoic membrane assay was performed to detect the in vivo anti-angiogenic effect. The expression of VEGF was measured by the enzyme-linked immunosorbent. RESULTS: Results showed that TF-SB inhibited the proliferation and migration of HUVECs in a dose- dependent manner. Simultaneously, TF-SB significantly suppressed HUVEC angiogenesis in vitro and in vivo. Furthermore, VEGF was downregulated in both HUVECs and MHCC97-H cells after TF-SB treatment. CONCLUSION: TF-SB could suppress the process of angiogenesis in vitro and in vivo. TF-SB potentially suppresses angiogenesis in HUVECs by regulating VEGF. These findings suggested that TF-SB may serve as a potent anti-angiogenic agent.

Protective effects of Scutellaria barbata against rat liver tumorigenesis.

Scutellaria barbata D. Don (S. barbata), a traditional Chinese medicine, is used to treat cancers, inflammation, and urinary diseases. This study aimed to determine any protective effects of S. barbata crude extract (CE-SB) against rat liver tumorigenesis induced by diethylnitrosamine (DENA). Liver malfunction indices in serum were measured by biochemical examination. Hematoxylin and eosin staining was performed to examine liver pathology. Contents of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured in liver homogenates to evaluate oxidative stress. The levels of liver malfunction indices in the CE-SB groups, especially in the CE-SB high dose group, were lower than that of the model group (P<0.05). The results from histological examination indicated that the number of liver nodules in the CE-SB groups decreased compared with the model group (P<0.05). Content of MDA determined in liver was significantly decreased, and level of SOD elevated by CE-SB. CE-SB can inhibit experimental liver tumorigenesis and relieve hepatic injury in rats.