The quorum sensing SinI/R system contributes to cadmium immobilization in Ensifer adhaerens NER9 in the cadmium-contaminated solution.

In this study, the cadmium (Cd)-tolerant Ensifer adhaerens strain NER9 with quorum sensing (QS) systems (responsible for N-acyl homoserine lactone (AHL) production) was characterized for QS system-mediated Cd immobilization and the underlying mechanisms involved. Whole-genome sequence analysis revealed that strain NER9 contains the QS SinI/R and TraI/R systems. Strains NER9 and the NER9∆sinI/R, NER9∆traI/R, and NER9∆sinI/R-traI/R mutants were constructed and compared for QS SinI/R and TraI/R system-mediated Cd immobilization in the solution and the mechanisms involved. After 24 h of incubation, strain NER9 significantly decreased the Cd concentration in the Cd-contaminated solution compared with the NER9∆sinI/R, NER9∆traI/R, and NER9∆sinI/R-traI/R mutants. The NER9∆sinI/R mutant had a greater impact on Cd immobilization and a lower impact on the activities of AHLs than did the NER9∆traI/R mutant. The NER9∆sinI/R mutant had significantly greater Cd concentrations and lower cell wall- and exopolysaccharide (EPS)-adsorbed Cd contents than did strain NER9. Furthermore, the NER9∆sinI/R mutant presented a decrease in the number of functional groups interacting with Cd, compared with strain NER9. These results suggested that the SinI/R system in strain NER9 contributed to Cd immobilization by mediating cell wall- and EPS-adsorption in Cd-containing solution.

Triggering receptor expressed on myeloid cells (TREM) like transcript-1 (TLT-1) reveals platelet activation in preeclampsia.

Triggering receptor expressed on myeloid cells (TREM) like transcript-1 (TLT-1) is a membrane protein receptor found in α-granules of megakaryocytes and platelets. Upon platelet activation TLT-1 is rapidly relocated to the surface of platelets. In plasma, a soluble form of TLT-1 (sTLT-1) is present. Plasma levels of sTLT-1 are significantly elevated in thrombotic diseases. In the present study, we investigated to whether TLT-1 reflects platelet activation in pregnant women with preeclampsia. We studied 30 preeclamptic patients who were matched with 30 normotensive pregnant women and 30 non-pregnant controls. Basal TLT-1, P-selectin, and CD63 expressions on platelets were analyzed with the use of flow-cytometry (FCM). Platelet reactivity was induced by thrombin receptor activation peptide and determined by FCM. Plasma concentrations of sTLT-1 and soluble P-selectin (sP-selectin) were measured by an enzyme-linked immunosorbent assay. Results show that basal platelet expression of TLT-1, P-selectin and CD63 were increased in women with preeclampsia (PE) compared with normotensive pregnant women (NP). Platelets from PE women and NP women were more responsive compared to from nonpregnant women controls (NC), and which was demonstrated by increased expression of TLT-1, P-selectin, and CD63 upon stimulation in vitro. Plasma concentration of sTLT-1 was greater in PE women compared to NP women and NC women. Plasma sP-selectin level was higher in pregnant women than in nonpregnant women, but there were no significant differences between PE and NP women. In summary, our results revealed that platelet activation is prominent in preeclampsia, TLT-1 reflects platelet activation and may be a useful indicator for preeclampsia.

Cadmium-resistant and arginine decarboxylase-producing endophytic Sphingomonas sp. C40 decreases cadmium accumulation in host rice (Oryza sativa Cliangyou 513).

In this study, an cadmium (Cd)-immobilizing and arginine decarboxylase-producing endophytic Sphingomonas sp. strain C40 obtained from the seeds of Oryza sativa Cliangyou 513 was characterized for its Cd availability and Cd uptake in host rice using hydroponic and soil experiments. The Cd concentration decreased by 51-95% compared to the control, while the spermidine concentration increased by 19-25% with Cd compared with no Cd in the strain C40-inoculated solution. Strain C40 decreased the above-ground tissue Cd content by 27-37% and increased spermine and spermidine contents by 28-67% and the expression levels of genes involved in spermine and spermidine production by 29-217% in rice roots compared to the controls. Furthermore, correlation analyses showed the significantly negative correlation between rice root spermine and spermidine contents and above-ground tissue Cd content. In the Cd-added soil, strain C40 promoted the rice biomass by 29-36% and decreased rice root, above-ground tissue, and grain Cd contents by 18, 16, and 33% and total grain Cd uptake by 14% compared with the controls at the maturity stage. Strain C40 decreased the exchangeable Cd content by 27% and increased the Fe and Mn oxides-bound Cd content by 45% in the rice rhizosphere soils at the maturity stage compared with the controls. These results suggested that the endophytic bacterial strain C40 increased rice root polyamine production and their related gene expression and the transformation of available Cd to unavailable Cd, leading to reduced Cd accumulation and translocation from the rice roots to grains.

Wheat-associated Pseudomonas taiwanensis WRS8 reduces cadmium uptake by increasing root surface cadmium adsorption and decreasing cadmium uptake and transport related gene expression in wheat.

Metal-resistant bacteria can reduce Cd accumulation in plants, but mechanisms underlying this effect are poorly understood. In this study, a highly effective Cd-resistant WRS8 strain was obtained from the rhizoshere soil of Triticum aestivum L. Yangmai-13 and identified as Pseudomonas taiwanensis based on 16S rRNA gene sequence analysis. Strain WRS8 was investigated for its effects on Cd availability and wheat tissue Cd contents and the related mechanisms using a hydroponic culture experiment. In strain WRS8-inoculated solution, the Cd concentration reduced and the pH and cell-adsorbed Cd increased with time. Strain WRS8 increased the wheat root and above-ground tissue dry weights by 11-36% compared to the controls. In strain WRS8-inoculated wheat plants, the Cd contents of the roots and above-ground tissues decreased by 78-85% and 88-94% and the Cd bioconcentration and translocation factors decreased by 78-85% and 46-58% at days 3 and 10, respectively, compared with the controls. The root surface-adsorbed Cd contents increased by 99-121% in the WRS8 strain-inoculated wheat plants at days 3 and 10 compared to the controls. Furthermore, strain WRS8 colonized the wheat root surfaces and interiors and reduced the expression levels of the LCT1 and HMA2 genes involved in Cd accumulation and transport in wheat roots by 46% and 30%, respectively, compared to the controls. In the Cd-contaminated soils, strain WRS8 significantly reduced the available Cd content by 20-24% and increased the pH compared to the controls. These findings showed the important role of strain WRS8 in reducing solution and soil Cd availability and suggested that strain WRS8 reduced the wheat tissue Cd accumulation by increasing root surface Cd adsorption and decreasing wheat root Cd uptake and transport-related gene expression and may provide a new and effective wheat rhizobacteria-enhanced approach for reducing wheat Cd uptake in Cd-polluted environments.

MicroRNA-510 Plays Oncogenic Roles in Non-Small Cell Lung Cancer by Directly Targeting SRC Kinase Signaling Inhibitor 1.

An increasing number of studies have demonstrated that microRNAs (miRNAs) may play key roles in various cancer carcinogenesis and progression, including non-small cell lung cancer (NSCLC). However, the expressions, roles, and mechanisms of miR-510 in NSCLC have, up to now, been largely undefined. In vivo assay showed that miR-510 was upregulated in NSCLC tissues compared with that in adjacent nontumor lung tissues. miR-510 expression was significantly correlated with TNM stage and lymph node metastasis. In vitro assay indicated that expressions of miR-510 were also increased in NSCLC cell lines. Downregulation of miR-510 suppressed NSCLC cell proliferation and invasion in vitro. We identified SRC kinase signaling inhibitor 1 (SRCIN1) as a direct target gene of miR-510 in NSCLC. Expression of SRCIN1 was downregulated in lung cancer cells and negatively correlated with miR-510 expression in tumor tissues. Downregulation of SRCIN1, leading to inhibition of miR-510 expression, reversed cell proliferation and invasion in NSCLC cells. These results showed that miR-510 acted as an oncogenic miRNA in NSCLC, partly by targeting SRCIN1, suggesting that miR-510 can be a potential approach for the treatment of patients with malignant lung cancer.

Altered circulating T follicular helper cells in patients with chronic immune thrombocytopenia.

The present study aimed to illuminate the role of circulating T follicular helper (TFH) cells in patients diagnosed with chronic immune thrombocytopenia (cITP). Fifty-four patients with cITP and 30 age-matched healthy control subjects were enrolled in the present study. TFH cell frequencies, expression of CD4+ TFH cell-associated cytokines, including interleukin (IL)-2, IL-4, IL-10 and IL-21 and associated regulatory mRNA expression levels including Bcl-6, c-Maf, Blimp-1 and PD-1 pre- and post-treatment with intravenous immunoglobulin and corticosteroids, were detected by flow cytometry, ELISA and reverse transcription-quantitative polymerase chain reaction, respectively. TFH cell frequencies of patients were significantly higher compared with healthy controls pre-treatment (P<0.05). Following treatment, significantly decreased percentages of TFH cells were present in cITP responders (P<0.05). Correlation analysis revealed that the number of TFH cells was negatively correlated with the platelet count in the peripheral blood. Furthermore, analysis of inflammatory cytokines indicated significant differences in serum interleukin (IL)-21 and IL-10 between pretreated patients and healthy controls (P<0.05). Additionally, transcription factor B-cell lymphoma (Bcl)-6, c-Maf and programmed death-ligand (PD)-1 mRNA expression levels were significantly different between cITP patients prior to treatment and the healthy controls (P<0.05). However, the expression levels of Bcl-6, C-Maf and PD-1 mRNA were significantly changed post-treatment (P<0.05). These data demonstrated that circulating TFH cells and CD4+ TFH cell-associated cytokines may serve a role in cITP. The findings suggest that the overactivation of TFH cells may contribute to the immunopathogenesis of cITP, thus blocking the pathway of TFH cells may be reasonable for therapeutic intervention.

Ralstonia eutropha Q2-8 reduces wheat plant above-ground tissue cadmium and arsenic uptake and increases the expression of the plant root cell wall organization and biosynthesis-related proteins.

In this study, the molecular mechanisms involved in Ralstonia eutropha Q2-8-induced increased biomass and reduced cadmium (Cd) and arsenic (As) uptake in wheat plants (Triticum aestivum cv. Yangmai 16) were investigated in growth chambers. Strain Q2-8 significantly increased plant biomass (22-75%) without and with Cd (5 µM) + As (10 µM) stress and reduced plant above-ground tissue Cd (37%) and As (34%) contents compared to those in the controls. Strain Q2-8 significantly increased the proportions of Cd and As in wheat root cell walls. Under Cd and As stress, 109 root proteins were differentially expressed among which those involved in metabolisms, stress and defence, and energy were dominant in the presence of strain Q2-8. Furthermore, energy-, defence-, and cell wall biosynthesis-related proteins were found to be up-regulated. Notably, differentially expressed cell wall biosynthesis-related proteins in roots were only found in bacteria-inoculated plants under Cd and As stress. The results suggest that strain Q2-8 can alleviate Cd and As toxicity to wheat plant seedlings and reduce above-ground tissue Cd and As uptake by increasing the efficiency of root energy metabolism, defence, and cell wall biosynthesis under Cd and As stress.

Identification of candidate biomarkers that involved in the epigenetic transcriptional regulation for detection gastric cancer by iTRAQ based quantitative proteomic analysis.

BACKGROUND: The sensitivities and specificities of biomarkers for gastric cancer are insufficient for clinical detection, and new diagnostics are therefore urgently required. METHODS: A discovery set of gastric cancer tissues was labeled with iTRAQ reagents, separated using SCX chromatography, and identified using LC-ESI-MS/MS. A validation set of gastric cancer tissues was used to confirm the expression levels of potential markers. RESULTS: The present study detected metastasis-associated protein 2 (MTA2) and Histone deacetylases 1 (HDAC1) proteins that were overexpressed in gastric cancer tissues compared with that in adjacent gastric tissue. The sensitivity and specificity of MTA2 in detecting 76 cases gastric cancers were 57.9% (95% CI: 46.5%-69.3%) and 55.3% (95% CI: 43.8%-66.7%), respectively. The sensitivity and specificity of HDAC1 were 61.8% (95% CI: 50.7%-73%) and 63.2% (95% CI: 52.1%-74.3%), respectively. The co-expression of MTA2 and HDAC1 in gastric cancer achieved 65.3% sensitivity (95% CI: 51.5%-79.1%) and 65.2% specificity (95% CI: 50.9%-79.5%), which was strongly associated with lymph node metastasis and TNM staging. CONCLUSION: The present findings indicated a tight correlation between the MTA2 and HDAC1 expression level and lymph node metastasis and TNM staging in gastric cancers. Therefore, MTA2 and HDAC1 might be predictors of lymph node metastasis phenotype and possible target molecule for anticancer drug design in human gastric cancer.

Saccharibacillus qingshengii sp. nov., isolated from a lead-cadmium tailing.

A Gram-stain-positive, strictly aerobic strain, H6T, was isolated from a soil sample of lead-cadmium tailing in Qixia district, Nanjing (China). Cells of the strain are rod-shaped and colonies on LB agar are red. Strain H6T has subpolar and polar flagella and the optimal condition for growth is 30 °C, with 1 % (w/v) NaCl and at pH 7.0. Based on the 16S rRNA gene sequences, phylogenetic analysis showed that strain H6T was closely related to the genus Saccharibacillus, and the closest relatives were Saccharibacillus deserti WLJ055T (99.0 % 16S rRNA gene sequence similarity), Saccharibacillus kuerlensis HR1T (97.0 %) and Saccharibacillus sacchari GR21T (96.4 %). The DNA-DNA relatedness value between strain H6T and S. deserti WLJ055T was 55.0 %. The major polar lipids of strain H6T were diphosphatidylglycerol, phosphatidylglycerol, phosphoglycolipid and three unknown glycolipids. The DNA G+C content was 58.4 mol% and MK-7 was the major isoprenoid quinone. The major fatty acids were anteiso-C15 : 0 and C16 : 0. meso-Diaminopimelic acid was detected in the peptidoglycan. Based on the phylogenetic, biochemical and chemotaxonomic data, strain H6T represents a novel species of the genus Saccharibacillus, for which the name Saccharibacillus qingshengii sp. nov., is proposed. The type strain is H6T (=CCTCC AB 2016001T=JCM 31172T).

Increased drug resistance in breast cancer by tumor-associated macrophages through IL-10/STAT3/bcl-2 signaling pathway.

Tumor-associated macrophages (TAMs) appear to be the major component in solid tumor microenvironment, which were reported to play an important role in tumor malignant progression. Recently, TAMs were reported to be associated with drug resistance in some types of solid tumor including breast cancer. However, how TAMs regulate breast tumor resistance remains unknown. In this study, THP-1 cells were stimulated with PMA and IL-4/IL-13 to form M2-like macrophages to study the role of TAMs on chemoresistance. Our results showed that TAMs and its supernatants significantly prevent breast tumor cells from apoptosis caused by paclitaxel. We also found that the high level of IL-10 secreted by TAMS was responsible for drug resistance of breast cancer. The possible TAMs-modulated drug resistance mechanism involved may be associated with elevation of bcl-2 gene expression and up-regulation of STAT3 signaling in tumor cells. Furthermore, the blockage of TAMs-derived IL-10 by neutralizing antibody resulted in attenuation of STAT3 activation and decrease of bcl-2 mRNA expression, consequently enhanced sensitivity of breast cancer cells. Our data suggested that TAMs might induce drug resistance through IL-10/STAT3/bcl-2 signaling pathway, providing possible new targets for breast tumor therapy.

Increased cadmium and lead uptake of a cadmium hyperaccumulator tomato by cadmium-resistant bacteria.

Two cadmium (Cd)-resistant strains Pseudomonas sp. RJ10 and Bacillus sp. RJ16 were investigated for their effects on the soil Cd and lead (Pb) solubilization and promotion of plant growth and Cd and Pb uptakes of a Cd-hyperaccumulator tomato. In the heavy metal-contaminated inoculated soil, the CaCl(2)-extractable Cd and Pb were increased by 58-104% and 67-93%, respectively, compared to the uninoculation control. The bacteria produced indole acetic acid, siderophore and 1-aminocyclopropane-1-carboxylate deaminase. Root elongation assay conducted on tomato under gnotobiotic conditions demonstrated increase in root elongation of inoculated tomato seedlings compared to the control plants. An increase in Cd and Pb contents of above-ground tissues varied from 92% to 113% and from 73% to 79% in inoculated plants growing in heavy metal-contaminated soil compared to the uninoculation control, respectively. These results show that the bacteria could be exploited for bacteria enhanced-phytoextraction of Cd- and Pb-polluted soils.

Effects of inoculation of biosurfactant-producing Bacillus sp. J119 on plant growth and cadmium uptake in a cadmium-amended soil.

A biosurfactant-producing Bacillus sp. J119 isolated from heavy metal contaminated soils was investigated for its effects on the plant growth-promoting characteristics and heavy metal and antibiotic resistance. A pot experiment was conducted for investigating the capability of the biosurfactant-producing bacterial strain Bacillus sp. J119 to promote the plant growth and cadmium uptake of rape, maize, sudangrass and tomato in soil artificially contaminated with different levels of cadmium (Cd) (0 and 50mgkg(-1)). The strain was found to exhibit different multiple heavy metal (Pb, Cd, Cu, Ni and Zn) and antibiotic (kanamycin, streptomycin, ampicillin, tetracycline and rifampin) resistance characteristics. The strain had the capacity to produce indole acetic acid (IAA) and siderophores. Cd treatment did not significantly decreased growth of tomato, maize and rape plants, but Cd treatment significantly decreased growth of sudangrass (p<0.05). In the Cd-added soil, above-ground biomass and root dry weights of tomatoes were increased by 24 and 59%, respectively, in live bacterial inoculation compared to dead bacterial inoculation control. There were no obvious differences in the above-ground tissue and root dry weight of maize and sudangrass between live bacterial inoculation and dead bacterial inoculation. In the soil treated with 50 mg Cdkg(-1), increase in above-ground tissue Cd content varied from 39 to 70% in live bacterium-inoculated plants compared to dead bacterium-inoculated control. In addition, among the inoculated plants, tomato was the greatest Cd accumulator. The bacterial strain was also able to colonize and develop in the rhizosphere soils after root inoculation.