The human gastrointestinal microbiota and prostate cancer development and treatment

The human gastrointestinal microbiome contains commensal bacteria and other microbiota that have been gaining increasing attention in the context of cancer development and response to treatment. Microbiota play a role in the maintenance of host barrier surfaces that contribute to both local inflammation and other systemic metabolic functions. In the context of prostate cancer, the gastrointestinal microbiome may play a role through metabolism of estrogen, an increase of which has been linked to the induction of prostatic neoplasia. Specific microbiota such as Bacteroides, Streptococcus, Bacteroides massiliensis, Faecalibacterium prausnitzii, Eubacterium rectalie, and Mycoplasma genitalium have been associated with differing risks of prostate cancer development or extensiveness of prostate cancer disease. In this Review, we discuss gastrointestinal microbiota’s effects on prostate cancer development, the ability of the microbiome to regulate chemotherapy for prostate cancer treatment, and the importance of using Next Generation Sequencing to further discern the microbiome’s systemic influence on prostate cancer

Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics

Background: Lipids have critical functions in cellular energy storage, structure and signaling. Many individual lipid molecules have been associated with the evolution of prostate cancer; however, none of them has been approved to be used as a biomarker. The aim of this study is to identify lipid molecules from hundreds plasma apparent lipid species as biomarkers for diagnosis of prostate cancer. Methodology/Principal Findings: Using lipidomics, lipid profiling of 390 individual apparent lipid species was performed on 141 plasma samples from 105 patients with prostate cancer and 36 male controls. High throughput data generated from lipidomics were analyzed using bioinformatic and statistical methods. From 390 apparent lipid species, 35 species were demonstrated to have potential in differentiation of prostate cancer. Within the 35 species, 12 were identified as individual plasma lipid biomarkers for diagnosis of prostate cancer with a sensitivity above 80%, specificity above 50% and accuracy above 80%. Using top 15 of 35 potential biomarkers together increased predictive power dramatically in diagnosis of prostate cancer with a sensitivity of 93.6%, specificity of 90.1% and accuracy of 97.3%. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) demonstrated that patient and control populations were visually separated by identified lipid biomarkers. RandomForest and 10-fold cross validation analyses demonstrated that the identified lipid biomarkers were able to predict unknown populations accurately, and this was not influenced by patient's age and race. Three out of 13 lipid classes, phosphatidylethanolamine (PE), ether-linked phosphatidylethanolamine (ePE) and ether-linked phosphatidylcholine (ePC) could be considered as biomarkers in diagnosis of prostate cancer. Conclusions/Significance: Using lipidomics and bioinformatic and statistical methods, we have identified a few out of hundreds plasma apparent lipid molecular species as biomarkers for diagnosis of prostate cancer with a high sensitivity, specificity and accuracy

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c

Inclusive production of ρ0(770),f0(980)\rho^{0}(770), f_0(980) and f2(1270)f_2(1270) mesons in νμ\nu_{\mu} charged current interactions

The inclusive production of the meson resonances $\rho^{0}(770)$, $f_0(980)$ and $f_2(1270)$ in neutrino-nucleus charged current interactions has been studied with the NOMAD detector exposed to the wide band neutrino beam generated by 450 GeV protons at the CERN SPS. For the first time the $f_{0}(980)$ meson is observed in neutrino interactions. The statistical significance of its observation is 6 standard deviations. The presence of $f_{2}(1270)$ in neutrino interactions is reliably established. The average multiplicity of these three resonances is measured as a function of several kinematic variables. The experimental results are compared to the multiplicities obtained from a simulation based on the Lund model. In addition, the average multiplicity of $\rho^{0}(770)$ in antineutrino - nucleus interactions is measured.Comment: 23 pages, 14 figures, 8 tables. To appear in Nucl. Phys.

Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology

Objective: Individuals with obesity and type 2 diabetes differ from lean and healthy individuals in their abundance of certain gut microbial species and microbial gene richness. Abundance of Akkermansia muciniphila, a mucin-degrading bacterium, has been inversely associated with bodyfat mass and glucose intolerance in mice, but more evidence is needed in humans. The impact of diet and weight loss on this bacterial species is unknown. Our objective was to evaluate the association between fecal A. muciniphila abundance, fecal microbiome gene richness, diet, host characteristics, and their changes after calorie restriction (CR). Design: The intervention consisted of a 6-week CR period followed by a 6-week weight stabilization (WS) diet in overweight and obese adults (N=49, including 41 women). Fecal A. muciniphila abundance, fecal microbial gene richness, diet and bioclinical parameters were measured at baseline and after CR and WS. Results: At baseline A. muciniphila was inversely related to fasting glucose, waist-to-hip ratio, and subcutaneous adipocyte diameter. Subjects with higher gene richness and A. muciniphila abundance exhibited the healthiest metabolic status, particularly in fasting plasma glucose, plasma triglycerides and body fat distribution. Individuals with higher baseline A. muciniphila displayed greater improvement in insulin sensitivity markers and other clinical parameters after CR. A. muciniphila was associated with microbial species known to be related to health. Conclusion: A. muciniphila is associated with a healthier metabolic status and better clinicaloutcomes after CR in overweight/obese adults, however the interaction between gut microbiota ecology and A. muciniphila has to be taken into account

Mineralization of vegetable oils used for thermal weed control in arable soils

Hot vegetable oil can be used for weed control as an alternative to the use of herbicides. We analysed the temporal development of vegetable oil mineralization in soil and tested the role of nutrient supply on oil mineralization. Further, we investigated the effect of oil application on mineralization of native soil organic carbon (SOC), i.e. the priming effect. In a laboratory experiment, three oil dosages (0.1, 1.0 and 3.0ml per 35g soil) were applied to three arable soils and soil respiration was measured hourly. Both a C3-sunflower oil and a C4-corn oil were used in order to differentiate oil-derived CO2 from SOC-derived CO2. The results revealed that after 42days of incubation, 9.6 to 39.7% of the applied oil was mineralized which, however, also primed the mineralization of SOC by a factor of 2.2 to 4.2. The higher the applied oil amount, the lower was the percentage of oil-C mineralization, but the higher was the priming effect. The addition of fertilizer (0.29mgNg(-1) soil and 0.048mgPg(-1) soil) increased oil-C mineralization to 39.9 to 50.9%. We conclude that oil can temporarily accumulate in soil, especially in case of low nutrient supply. As the addition of oil stimulates SOC mineralization, a decrease of native SOC stocks may occur, which needs further quantification in long-term field experiments.Peer reviewe

AÇÃO DE EXTENSÃO PARA INCENTIVAR A LEITURA

O projeto de extensão “QUARTAS LITERÁRIAS” foi desenvolvido em 2013pela Prof.ª Dr.ª Gizelle Kaminski Corso3 e coordenado pela Prof.ª Me. Chris RoyesSchardosim, no Instituto Federal Catarinense – Câmpus Ibirama. O objetivo principalfoi desenvolver um trabalho de promoção da leitura, principalmente comestudantes dos anos finais do ensino fundamental (LDB 9394/96), via oficinasde leitura ministradas pela bolsista Graziele de Castro Graessler, estudante doEnsino Médio Integrado no curso de Vestuário, a qual atua como mediadora daleitura, sob supervisão da professora coordenadora do projeto e auxílio das outrasduas professoras participantes, Prof.ª Me. Cleonice Marisa de Brito Näedzoldde Souza e Prof.ª Sonia Schappo Imhof.Além de buscar o interesse pela leitura nos jovens, o projeto pretendeudar mais visibilidade ao IFC na cidade, já que o Câmpus Ibirama iniciou suasatividades, recentemente, em 2010, bem como caracterizá-lo como um espaçopúblico de produção e disseminação do conhecimento

Plasma lysophosphatidylcholine levels are reduced in obesity and type 2 diabetes

BACKGROUND: Obesity and type 2 diabetes (T2DM) are associated with increased circulating free fatty acids and triacylglycerols. However, very little is known about specific molecular lipid species associated with these diseases. In order to gain further insight into this, we performed plasma lipidomic analysis in a rodent model of obesity and insulin resistance as well as in lean, obese and obese individuals with T2DM. METHODOLOGY/PRINCIPAL FINDINGS: Lipidomic analysis using liquid chromatography coupled to mass spectrometry revealed marked changes in the plasma of 12 week high fat fed mice. Although a number of triacylglycerol and diacylglycerol species were elevated along with of a number of sphingolipids, a particularly interesting finding was the high fat diet (HFD)-induced reduction in lysophosphatidylcholine (LPC) levels. As liver, skeletal muscle and adipose tissue play an important role in metabolism, we next determined whether the HFD altered LPCs in these tissues. In contrast to our findings in plasma, only very modest changes in tissue LPCs were noted. To determine when the change in plasma LPCs occurred in response to the HFD, mice were studied after 1, 3 and 6 weeks of HFD. The HFD caused rapid alterations in plasma LPCs with most changes occurring within the first week. Consistent with our rodent model, data from our small human cohort showed a reduction in a number of LPC species in obese and obese individuals with T2DM. Interestingly, no differences were found between the obese otherwise healthy individuals and the obese T2DM patients. CONCLUSION: Irrespective of species, our lipidomic profiling revealed a generalized decrease in circulating LPC species in states of obesity. Moreover, our data indicate that diet and adiposity, rather than insulin resistance or diabetes per se, play an important role in altering the plasma LPC profile

Repeated lipoprotein apheresis and immune response: Effects on different immune cell populations

Background: Atherosclerosis is considered a chronic inflammation of arterial vessels with the involvement of several immune cells causing severe cardiovascular diseases. Lipoprotein apheresis (LA) improves cardiovascular conditions of patients with severely disturbed lipid metabolism. In this context, little is known about the impact of LA on various immune cell populations, especially over time. Methods: Immune cells of 18 LA-naïve patients starting weekly LA treatment were analyzed before and after four apheresis cycles over the course of 24 weeks by flow cytometry. Results and Conclusions: An acute lowering effect of LA on T cell and natural killer (NK) cell subpopulations expressing CD69 was observed. The nonclassical and intermediate monocyte subsets as well as HLA-DR+ 6-sulfo LacNAc+ monocytes were significantly reduced during the apheresis procedure. We conclude that LA has the capacity to alter various immune cell subsets. However, LA has mainly short-term effects than long-term consequences on proportions of immune cells

Top-Down Lipidomics Reveals Ether Lipid Deficiency in Blood Plasma of Hypertensive Patients

BACKGROUND: Dyslipoproteinemia, obesity and insulin resistance are integrative constituents of the metabolic syndrome and are major risk factors for hypertension. The objective of this study was to determine whether hypertension specifically affects the plasma lipidome independently and differently from the effects induced by obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: We screened the plasma lipidome of 19 men with hypertension and 51 normotensive male controls by top-down shotgun profiling on a LTQ Orbitrap hybrid mass spectrometer. The analysis encompassed 95 lipid species of 10 major lipid classes. Obesity resulted in generally higher lipid load in blood plasma, while the content of tri- and diacylglycerols increased dramatically. Insulin resistance, defined by HOMA-IR >3.5 and controlled for BMI, had little effect on the plasma lipidome. Importantly, we observed that in blood plasma of hypertensive individuals the overall content of ether lipids decreased. Ether phosphatidylcholines and ether phosphatidylethanolamines, that comprise arachidonic (20:4) and docosapentaenoic (22:5) fatty acid moieties, were specifically diminished. The content of free cholesterol also decreased, although conventional clinical lipid homeostasis indices remained unaffected. CONCLUSIONS/SIGNIFICANCE: Top-down shotgun lipidomics demonstrated that hypertension is accompanied by specific reduction of the content of ether lipids and free cholesterol that occurred independently of lipidomic alterations induced by obesity and insulin resistance. These results may form the basis for novel preventive and dietary strategies alleviating the severity of hypertension