Nutritional metabonomics: applications and perspectives

Nowadays, nutrition focuses on improving health of individuals through diet. Current nutritional research aims at health promotion, disease prevention, and performance improvement. Modern analytical platforms allow the simultaneous measurement of multiple metabolites providing new insights in the understanding of the functionalities of cells and whole organisms. Metabonomics, "the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modifications", provides a systems approach to understanding global metabolic regulations of organisms. This concept has arisen from various applications of NMR and MS spectroscopies to study the multicomponent metabolic composition of biological fluids, cells, and tissues. The generated metabolic profiles are processed by multivariate statistics to maximize the recovery of information to be correlated with well-determined stimuli such as dietary intervention or with any phenotypic data or diet habits. Metabonomics is thus uniquely suited to assess metabolic responses to deficiencies or excesses of nutrients and bioactive components. Furthermore, metabonomics is used to characterize the metabolic phenotype of individuals integrating genetic polymorphism, metabolic interactions with commensal and symbiotic partners such as gut microflora, as well as environmental and behavioral factors including dietary preferences. This paper reports several experimental key aspects in nutritional metabonomics, reviews its applications employing targeted and holistic approach analysis for the study of the metabolic responses following dietary interventions. It also reports the assessment of intra- and inter-individual variability in animal and human populations. The potentialities of nutritional metabonomics for the discovery of new biomarkers and the characterization of metabolic phenotypes are discussed in a context of their possible utilizations for personalized nutrition to provide health maintenance at the individual level.     

Recovery of soil streptomycetes from arid habitats in Jordan and their potential to inhibit multi-drug resistant <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> pathogens

A total of 161 different Streptomyces isolates were recovered from 5 soil samples representing the driest habitats of Jordan. These were then characterized and assessed for their antagonistic activity against four clinical multi-drug resistant Pseudomonas aeruginosa test pathogens. Results indicated that only 3 strains out of 139 and 6 out of 22 isolated at 27°C and 45°C, respectively, were active against at least three strains of pathogenic Pseudomonas. However, three Streptomyces strains (J_2b, J₄, and J₁₂) that were isolated at 45°C inhibited all of the tested pathogens with an inhibition zone ranging between 5 and 16 mm in diameter. Data obtained from comparing the inhibition activity of these unique Streptomyces strains toward multi-resistant Pseudomonas pathogens with standard used antibiotics revealed that these isolates produce possible different inhibitory bioactive compounds other than the standard antibiotics.     

Total calcium-sensing receptor expression in circulating monocytes is increased in rheumatoid arthritis patients with severe coronary artery calcification

Introduction

Human circulating monocytes express the calcium-sensing receptor (CaSR) and are involved in atherosclerosis. This study investigated the potential association between vascular calcification in rheumatoid arthritis (RA) and CaSR expression in circulating monocytes.

Methods

In this cross-sectional study, 50 RA patients were compared to 25 control subjects matched for age and gender. Isolation of peripheral blood mononuclear cells and flow cytometry analysis were performed to study the surface and total CaSR expression in circulating monocytes. Coronary artery calcium (CAC) and abdominal aortic calcification (AAC) scores were evaluated by computed tomography and an association between these scores and the surface and/or total CaSR expression in circulating monocytes in RA patients was investigated.

Results

The two groups were similar in terms of age (RA: 60.9 ± 8.3 years, versus controls: 59.6 ± 5.3 years) and gender (RA: 74.0% females versus 72.0% females). We did not find a higher prevalence and greater burden of CAC or AAC in RA patients versus age- and gender-matched controls. When compared with control subjects, RA patients did not exhibit greater total CaSR (101.6% ± 28.8 vs. 99.9% ± 22.0) or surface CaSR (104.6% ± 20.4 vs. 99.9% ± 13.7) expression, but total CaSR expression in circulating monocytes was significantly higher in RA patients with severe CAC (Agatston score ≥200, n = 11) than in patients with mild-to-moderate CAC (1 to 199, n = 21) (P = 0.01).

Conclusions

This study demonstrates for the first time that total CaSR expression in human circulating monocytes is increased in RA patients with severe coronary artery calcification.     

A mathematical model of actin filament turnover for fitting FRAP data

A novel mathematical model of the actin dynamics in living cells under steady-state conditions has been developed for fluorescence recovery after photobleaching (FRAP) experiments. As opposed to other FRAP fitting models, which use the average lifetime of actins in filaments and the actin turnover rate as fitting parameters, our model operates with unbiased actin association/dissociation rate constants and accounts for the filament length. The mathematical formalism is based on a system of stochastic differential equations. The derived equations were validated on synthetic theoretical data generated by a stochastic simulation algorithm adapted for the simulation of FRAP experiments. Consistent with experimental findings, the results of this work showed that (1) fluorescence recovery is a function of the average filament length, (2) the F-actin turnover and the FRAP are accelerated in the presence of actin nucleating proteins, (3) the FRAP curves may exhibit both a linear and non-linear behaviour depending on the parameters of actin polymerisation, and (4) our model resulted in more accurate parameter estimations of actin dynamics as compared with other FRAP fitting models. Additionally, we provide a computational tool that integrates the model and that can be used for interpretation of FRAP data on actin cytoskeleton.     

Power generation using spinel manganese-cobalt oxide as a cathode catalyst for microbial fuel cell applications

This study focused on the use of spinel manganese-cobalt (Mn-Co) oxide, prepared by a solid state reaction, as a cathode catalyst to replace platinum in microbial fuel cells (MFCs) applications. Spinel Mn-Co oxides, with an Mn/Co atomic ratios of 0.5, 1, and 2, were prepared and examined in an air cathode MFCs which was fed with a molasses-laden synthetic wastewater and operated in batch mode. Among the three Mn-Co oxide cathodes and after 300 h of operation, the Mn-Co oxide catalyst with Mn/Co atomic ratio of 2 (MnCo-2) exhibited the highest power generation 113 mW/m2 at cell potential of 279 mV, which were lower than those for the Pt catalyst (148 mW/m2 and 325 mV, respectively). This study indicated that using spinel Mn-Co oxide to replace platinum as a cathodic catalyst enhances power generation, increases contaminant removal, and substantially reduces the cost of MFCs.     

Kidney Function Decline and Apparent Treatment-Resistant Hypertension in the Elderly

Background

Cross-sectional studies show a strong association between chronic kidney disease and apparent treatment-resistant hypertension, but the longitudinal association of the rate of kidney function decline with the risk of resistant hypertension is unknown.

Methods

The population-based Three-City included 8,695 participants older than 65 years, 4265 of them treated for hypertension. We estimated the odds ratios (OR) of new-onset apparent treatment-resistant hypertension, defined as blood pressure ≥ 140/90 mmHg despite use of 3 antihypertensive drug classes or ≥ 4 classes regardless of blood pressure, associated with the mean estimated glomerular filtration rate (eGFR) level and its rate of decline over 4 years, compared with both controlled hypertension and uncontrolled nonresistant hypertension with ≤ 2 drugs. GFR was estimated with three different equations.

Results

Baseline prevalence of apparent treatment-resistant hypertension and of controlled and uncontrolled nonresistant hypertension, were 6.5%, 62.3% and 31.2%, respectively. During follow-up, 162 participants developed apparent treatment-resistant hypertension. Mean eGFR decline with the MDRD equation was 1.5±2.9 mL/min/1.73 m² per year: 27.7% of the participants had an eGFR ≥3 and 10.1% ≥ 5 mL/min/1.73 m² per year. After adjusting for age, sex, obesity, diabetes, and cardiovascular history, the ORs for new-onset apparent treatment-resistant hypertension associated with a mean eGFR level, per 15 mL/min/1.73m² drop, were 1.23 [95% confidence interval 0.91–1.64] compared to controlled hypertension and 1.10 [0.83–1.45] compared to uncontrolled nonresistant hypertension; ORs associated with a decline rate ≥ 3 mL/min/1.73m² per year were 1.89 [1.09–3.29] and 1.99 [1.19–3.35], respectively. Similar results were obtained when we estimated GFR with the CKDEPI and the BIS1 equations. ORs tended to be higher for an eGFR decline rate ≥ 5 mL/min/1.73m² per year.

Conclusion

The speed of kidney function decline is associated more strongly than kidney function itself with the risk of apparent treatment-resistant hypertension in the elderly.     

Molecular characteristics of extended-spectrum β-lactamase-producing Escherichia coli in Riyadh: emergence of CTX-M-15-producing E. coli ST131

Background

The prevalence of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) has increased recently. The aim of this study was to further characterise and to assess the occurrence of ESBL-EC in Riyadh, to use pulsed field gel electrophoresis (PFGE) typing to investigate the epidemiology of ESBL-EC and to determine the prevalence of ST131 in ESBL-EC.

Methods

A total of 152 E. coli isolates were collected at a tertiary hospital in Riyadh from September 2010 to June 2011. Genotypic and phenotypic methods were used to characterise ESBLs. PFGE was used to determine genetic relatedness. Detection of ST131 and CTX-M-like ESBLs was performed using real-time PCR.

Results

Of 152 strains, 31 were positive for ESBLs by phenotypic methods. The bla _CTX-M-15 gene was highly prevalent (30/31 strains, 96.77%) among the 31 ESBL-positive E. coli strains. The bla _CTX-M-27 gene was detected in one strain. Twenty (64.5%) out of 31 of ESBL-EC were ST131. PFGE revealed 29 different pulsotypes.

Conclusions

Our study documented the high prevalence of ESBLs in E. coli isolates, with CTX-M-15 as the predominant ESBL gene. ST131 clone producing CTX-M-15 has a major presence in our hospital. The high prevalence of CTX-M producers was not due to the spread of a single clone. To the best of our knowledge, this study represents the first report of CTX-M-15 and CTX-M-27 β-lactamases and the detection of the ST131 clone in Saudi E. coli isolates.     

Top‐down systems biology integration of conditional prebiotic modulated transgenomic interactions in a humanized microbiome mouse model

Gut microbiome–host metabolic interactions affect human health and can be modified by probiotic and prebiotic supplementation. Here, we have assessed the effects of consumption of a combination of probiotics (Lactobacillus paracasei or L. rhamnosus) and two galactosyl‐oligosaccharide prebiotics on the symbiotic microbiome–mammalian supersystem using integrative metabolic profiling and modeling of multiple compartments in germ‐free mice inoculated with a model of human baby microbiota. We have shown specific impacts of two prebiotics on the microbial populations of HBM mice when co‐administered with two probiotics. We observed an increase in the populations of Bifidobacterium longum and B. breve, and a reduction in Clostridium perfringens, which were more marked when combining prebiotics with L. rhamnosus. In turn, these microbial effects were associated with modulation of a range of host metabolic pathways observed via changes in lipid profiles, gluconeogenesis, and amino‐acid and methylamine metabolism associated to fermentation of carbohydrates by different bacterial strains. These results provide evidence for the potential use of prebiotics for beneficially modifying the gut microbial balance as well as host energy and lipid homeostasis.     

Season- and latitude-dependent effects of simulated twilights on circadian entrainment

Groups of Syrian hamsters were exposed to LD cycles with twilight transitions and photoperiods simulating natural lighting conditions at the summer solstice (SS), equinox, and winter solstice (WS) at 41 degrees N and at the winter solstice at the Arctic Circle (WS 66 degrees N) but with daytime illuminance truncated at 10 lux (LD-twilight). Separate groups were kept under matching rectangular cycles (LD-rectangular). The inclusion of twilights affected several circadian parameters in a season-and latitude-dependent manner. The most striking difference was in the timing of activity onsets, which followed dusk in the presence of twilights but were more closely related to dawn (lights-on) in their absence. Activity offsets and midpoints were also earlier in LD-twilight than in LD-rectangular, with the differences being most pronounced under WS 66 degrees N. In LD-twilight, longer nights resulted in earlier offsets and midpoints, but in LD-rectangular, midpoints were later under long than under short nights while offsets did not vary significantly. In LD-twilight, activity duration (alpha) increased monotonically with increasing nighttime duration, but in LD-rectangular, alpha was shorter under WS 66 degrees N than under WS conditions. These effects of season and latitude observed in LD-twilight were similar to those reported in animals exposed to natural illumination, while those observed in LD-rectangular differed in several respects. The presence of twilights also resulted in lower day-to-day variability in activity onset times (greater precision), supporting the earlier conclusion that twilights increase the strength of the LD zeitgeber. Free-running periods in constant darkness (DD) were shorter in LD-twilight than in LD-rectangular, especially under WS 66 degrees N, raising the possibility that the effects of twilights on the timing of the entrained activity rhythm reflect their effects on the period of that rhythm. Increasing daytime illuminance to 100 lux (WS conditions only) resulted in earlier activity offsets and midpoints and a shorter alpha but had no effect on activity onsets or on subsequent period in DD. These results indicate that exposure to low twilight illuminances alone can account for several of the documented differences between the effects of natural and rectangular light cycles on circadian entrainment.