Bacterial-fungal interactions are widely found in distinct environments and contribute to ecosystem processes. Previous studies of these interactions have mostly been performed in soil, and only limited studies of aerial plant tissues have been conducted. Here we show that a seed-borne plant pathogenic bacterium, Burkholderia glumae (Bg), and an air-borne plant pathogenic fungus, Fusarium graminearum (Fg), interact to promote bacterial survival, bacterial and fungal dispersal, and disease progression on rice plants, despite the production of antifungal toxoflavin by Bg. We perform assays of toxoflavin sensitivity, RNA-seq analyses, lipid staining and measures of triacylglyceride content to show that triacylglycerides containing linolenic acid mediate resistance to reactive oxygen species that are generated in response to toxoflavin in Fg. As a result, Bg is able to physically attach to Fg to achieve rapid and expansive dispersal to enhance disease severity.
Abstract:It is well known that fucoidan, a natural sulfated polysaccharide present in various brown algae, mediates anticancer effects through the induction of cell cycle arrest and apoptosis. Nevertheless, the role of tumor suppressor p53 in the mechanism action of fucoidan remains unclear. Here, we investigated the anticancer effect of fucoidan on two p53 isogenic HCT116 (p53+/+ and p53−/−) cell lines. Our results showed that inhibition of cell viability, induction of apoptosis and DNA damage by treatment with fucoidan were similar in two cell lines. Flow cytometric analysis revealed that fucoidan resulted in G1 arrest in the cell cycle progression, which correlated with the inhibition of phosphorylation of retinoblastoma protein (pRB) and concomitant association of pRB with the transcription factor E2Fs. Furthermore, treatment with fucoidan obviously upregulated the expression of cyclin-dependent kinase (CDK) inhibitors, such as p21WAF1/CIP1 and p27KIP1, which was paralleled by an enhanced binding with CDK2 and CDK4. These events also commonly occurred in both cell lines, suggesting that fucoidan triggered G1 arrest and apoptosis in HCT116 cells by a p53-independent mechanism. Thus, given that most tumors exhibit functional p53 inactivation, fucoidan could be a possible therapeutic option for cancer treatment regardless of the p53 status.
The effects of conjugated linoleic acid (CLA) with other fatty acids on the fatty acid composition of egg yolk and on egg quality characteristics were studied in 5 groups: 1) CLA 0% (control), 2) CLA 2%, 3) CLA 2%+oleic acid (OA) 2% (CLA+OA), 4) CLA 2%+linoleic acid (LA) 2% (CLA+LA), and 5) CLA 2%+alpha-linolenic acid (LNA) 2% (CLA+LNA). Some parameters of egg quality such as shell thickness, shell strength, yolk color, yolk index, egg diameter, and Haugh units were aggravated when CLA was fed alone, but the quality was improved when CLA was combined with some other fatty acids. The egg production rate, which was decreased by feeding CLA alone, was improved by co-supplementation with LA or OA. An increase in CLA content was observed in all the dietary groups fed CLA for 2 wk. Feeding hens with CLA+LNA led to a linear increase in CLA content in the egg yolk after the fourth week of the feeding trial. Egg yolks from hens given CLA had considerably higher amounts of saturated fatty acids and lower amounts of monounsaturated fatty acids than egg yolks from the control group. The pattern of change in CLA concentration during the feeding trial was similar to the level of C18:0, which was inversely correlated with the level of C18:1. The unsaturated fatty acid co-supplementation strategy applied in this study offers insight into the mechanism of CLA accumulation in the egg yolk without apparent adverse effects on egg quality and egg production.
The purpose of this study was to evaluate the role of high-resolution magic angle spinning (HR-MAS) 1H nuclear magnetic resonance (NMR) spectroscopy in patients with ductal carcinoma in situ (DCIS) diagnosed on preoperative biopsy. We investigated whether the metabolic profiling of tissue samples using HR-MAS 1H NMR spectroscopy could be used to distinguish between DCIS lesions with or without an invasive component. Our institutional review board approved this combined retrospective and prospective study. Tissue samples were collected from 30 patients with pure DCIS and from 30 with DCIS accompanying invasive carcinoma. All patients were diagnosed with DCIS by preoperative core-needle biopsy and underwent surgical resection. The metabolic profiling of tissue samples was performed by HR-MAS 1H NMR spectroscopy. All observable metabolite signals were identified and quantified in all tissue samples. Metabolite intensity normalized by total spectral intensities was compared according to the tumor type using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). By univariate analysis, the metabolite concentrations of choline-containing compounds obtained with HR-MAS 1H NMR spectroscopy did not differ significantly between the pure DCIS and DCIS accompanying invasive carcinoma groups. However, the GPC/PC ratio was higher in the pure DCIS group than in the DCIS accompanying invasive carcinoma group (p = 0.004, Bonferroni-corrected p = 0.064), as well as the concentration of myo-inositol and succinate. By multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles could clearly discriminate between pure DCIS and DCIS accompanying invasive carcinoma. Our preliminary results suggest that HR-MAS MR metabolomics on breast tissue may be able to distinguish between DCIS lesions with or without an invasive component.
High-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy is a useful tool for investigating the metabolism of various cancers. Basal cell carcinoma (BCC) is the most common skin cancer. However, to our knowledge, data on metabolic profiling of BCC have not been reported in the literature. The objective of the present study was to investigate the metabolic profiling of cutaneous BCC using HR-MAS 1H NMR spectroscopy. HR-MAS 1H NMR spectroscopy was used to analyze the metabolite profile and metabolite intensity of histopathologically confirmed BCC tissues and normal skin tissue (NST) samples. The metabolic intensity normalized to the total spectral intensities in BCC and NST was compared, and multivariate analysis was performed with orthogonal partial least-squares discriminant analysis (OPLS-DA). P values < 0.05 were considered statistically significant. Univariate analysis revealed 9 metabolites that showed statistically significant difference between BCC and NST. In multivariate analysis, the OPLS-DA models built with the HR-MAS NMR metabolic profiles revealed a clear separation of BCC from NST. The receiver operating characteristic curve generated from the results revealed an excellent discrimination of BCC from NST with an area under the curve (AUC) value of 0.961. The present study demonstrated that the metabolite profile and metabolite intensity differ between BCC and NST, and that HR-MAS 1H NMR spectroscopy can be a valuable tool in the diagnosis of BCC.
High-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopy data may serve as a biomarker for breast cancer, with only a small volume of tissue sample required for assessment. However, previous studies utilized only a single tissue sample from each patient. The aim of this study was to investigate whether intratumoral location and biospecimen type affected the metabolic characterization of breast cancer assessed by HR-MAS MR spectroscopyThis prospective study was approved by the institutional review board and informed consent was obtained. Preoperative core-needle biopsies (CNBs), central, and peripheral surgical tumor specimens were prospectively collected under ultrasound (US) guidance in 31 patients with invasive breast cancer. Specimens were assessed with HR-MAS MR spectroscopy. The reliability of metabolite concentrations was evaluated and multivariate analysis was performed according to intratumoral location and biospecimen type.There was a moderate or higher agreement between the relative concentrations of 94.3% (33 of 35) of metabolites in the center and periphery, 80.0% (28 of 35) of metabolites in the CNB and central surgical specimens, and 82.9% (29 of 35) of metabolites between all 3 specimen types. However, there was no significant agreement between the concentrations of phosphocholine (PC) and phosphoethanolamine (PE) in the center and periphery. The concentrations of several metabolites (adipate, arginine, fumarate, glutamate, PC, and PE) had no significant agreement between the CNB and central surgical specimens.In conclusion, most HR-MAS MR spectroscopic data do not differ based on intratumoral location or biospecimen type. However, some metabolites may be affected by specimen-related variables, and caution is recommended in decision-making based solely on metabolite concentrations, particularly PC and PE. Further validation through future studies is needed for the clinical implementation of these biomarkers based on data from a single tissue sample.
Estrogen receptor (ER)-positive breast cancers overall have a good prognosis, however, some patients suffer relapses and do not respond to endocrine therapy. The purpose of this study was to determine whether there are any correlations between high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) metabolic profiles of core needle biopsy (CNB) specimens and the molecular markers currently used in patients with ER-positive breast cancers. The metabolic profiling of CNB samples from 62 ER-positive cancers was performed by HR-MAS MRS. Metabolic profiles were compared according to human epidermal growth factor receptor 2 (HER2) and Ki-67 status, and luminal type, using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). In univariate analysis, the HER2-positive group was shown to have higher levels of glycine and glutamate, compared to the HER2-negative group (P<0.01, and P <0.01, respectively). The high Ki-67 group showed higher levels of glutamate than the low Ki-67 group without statistical significance. Luminal B cancers showed higher levels of glycine (P=0.01) than luminal A cancers. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the subgroups according to HER2 and Ki-67 status, and luminal type. This study showed that the metabolic profiles of CNB samples assessed by HR-MAS MRS can be used to detect potential prognostic biomarkers as well as to understand the difference in metabolic mechanism among subtypes of ER-positive breast cancer.
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