PubMed

Potential biomarkers of Parkinson's disease revealed by plasma metabolic profiling. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Feb 02;1081-1082:101-108 Authors: Zhao H, Wang C, Zhao N, Li W, Yang Z, Liu X, Le W, Zhang X Abstract The plasma of Parkinson's disease (PD) patients may contain various altered metabolites associated with the risk or progression of the disease. Characterization of the abnormal metabolic pattern in PD plasma is therefore critical for the search for potential PD biomarkers. We collected blood plasma samples from PD patients and used an LC-MS based metabolomics approach to identify 17 metabolites with significantly altered levels. Metabolic network analysis was performed to place the metabolites linked to different pathways. The metabolic pathways involved were associated with tyrosine biosynthesis, glycerol phospholipid metabolism, carnitine metabolism and bile acid biosynthesis, within which carnitine and bile acid metabolites as potential biomarkers are first time reported. These abnormal metabolic changes in the plasma of patients with PD were mainly related to lipid metabolism and mitochondrial function. PMID: 29518718 [PubMed - as supplied by publisher]

1H-nuclear magnetic resonance metabolomics revealing the intrinsic relationships between neurochemical alterations and neurobehavioral and neuropathological abnormalities in rats exposed to tris(2-chloroethyl)phosphate. Chemosphere. 2018 Feb 09;200:649-659 Authors: Yang W, Zhao F, Fang Y, Li L, Li C, Ta N Abstract Tris(2-chloroethyl)phosphate (TCEP) is a widely used environmental organic pollutant. Studies have revealed the presence of both TCEP and its metabolites in environmental media. The neurotoxicity of TCEP has been investigated in vitro but rarely in mammals. This study aimed to determine the neurotoxic effects of TCEP on rats and to explore the possible intrinsic relationships between neurochemical alterations and the neurotoxic effects. For this, 6-week-old female SD rats were administered 50, 100, or 250 mg/kg/d TCEP daily by oral gavage for 60 days. TCEP exposure produced neurotoxicity in the female SD rats. The Morris water maze results revealed a dose-dependent decline in spatial learning and memory functions of exposed rats. In addition, pathological examination of the brain showed apoptotic and necrotic lesions in the CA1 field pyramidal cells of the hippocampus; further, rats treated with the highest TCEP dose showed inflammatory cells and calcified/ossified foci in the cortex areas. Furthermore, 1H-nuclear magnetic resonance metabolomics results revealed that TCEP exposure interfered with normal biological processes, including amino acid and neurotransmitter metabolism, energy metabolism, and cell membrane function integrity by changing the concentrations of glutamate, γ-aminobutyric acid, N-acetyl-d-aspartate, creatine, and lactic acid metabolites in the brain of treated rats. However, the changes in the concentrations of taurine, myo-inositol, creatine, and choline metabolites, which are associated with antioxidant physiological processes, might be a neuroprotective mechanism to prevent the neurotoxicity induced by TCEP. Thus, metabolomics combined with neuropathology and neurobehavioral analyses provided critical insights to investigate the TCEP-induced neurotoxic effects and mechanisms. PMID: 29518649 [PubMed - as supplied by publisher]

Identification of ethanol tolerant outer membrane proteome reveals OmpC-dependent mechanism in a manner of EnvZ/OmpR regulation in Escherichia coli. J Proteomics. 2018 Mar 05;: Authors: Zhang DF, Ye JZ, Dai HH, Lin XM, Li H, Peng XX Abstract Ethanol is an efficient disinfectant, but long-term and wide usage of ethanol leads to microbial tolerance. Bacteria with the tolerance are widely identified. However, mechanisms of the tolerance are not elucidated. To explore the mechanisms of outer membrane (OM) proteins underlying ethanol tolerance in bacteria, functional proteomic methodologies were utilized to characterize OM proteins of E. coli suddenly exposed to 3.125% ethanol. Of eleven proteins altered significantly, seven were OM proteins, in which LamB, FadL and OmpC were up-regulated, and OmpT, OmpF, Tsx and OmpA were down-regulated. The alterations were validated using Western blot. Then, functional characterization of the altered abundance of OM proteins was investigated in gene-deleted and gene-complemented mutants cultured in 1.56-6.25% ethanol. Higher inhibiting rate was detected in ΔompC than ΔlamB and ΔompA, but no difference was found between Δtsx, ΔompF, ΔfadL or ΔompT and control. Furthermore, EnvZ/OmpR two-component signal transduction system, which regulates OmpC and OmpF expression, was determined to participate in the tolerance. Finally, our results show that absence of envZ, ompR or ompC and ompA led to elevated and reduced intracellular ethanol, respectively. These findings indicate EnvZ-dependent phosphotransfer signaling pathway of the OmpR-mediated expression of OmpC plays a crucial role in ethanol tolerance. BIOLOGICAL SIGNIFICANCE: Ethanol tolerance is an adaptation strategy of bacteria. In the present study, we used the proteomic approaches involving 2-DE and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) to determined outer membrane (OM) protein changes in E. coli K-12 after 2 h of 1/2 MIC of ethanol exposure. Under ethanol stress, seven differential OM proteins were found, which were validated by Western blot. Functions of these seven OM proteins were compared using their genetically modified strains. Furthermore, the role of EnvZ/OmpR two-component signal transduction system was identified in ethanol tolerance of E. coli. Finally, Loss of ompC, envZ or ompR increases intracellular ethanol, while absence of ompA reduces reversal effect. This is the first report of OM proteomics in E. coli exposed to ethanol. Our findings reveal an unknown OmpC-dependent mechanism of ethanol tolerance in a manner of EnvZ/OmpR regulation. PMID: 29518576 [PubMed - as supplied by publisher]

Predictive biomarkers for type 2 of diabetes mellitus: bridging the gap between systems research and personalized medicine. J Proteomics. 2018 Mar 05;: Authors: Kraniotou C, Karadima V, Bellos G, Tsangaris GT Abstract The global incidence of metabolic disorders like type 2 diabetes mellitus (DM2) has assumed epidemic proportions, leading to adverse health and socio-economic impacts. It is therefore of critical importance the early diagnosis of DM2 patients and the detection of those at increased risk of disease. In this respect, Precision Medicine (PM) is an emerging approach that includes practices, tests, decisions and treatments adapted to the characteristics of each patient. With regard to DM2, PM manages a wealth of "omics" data (genomic, metabolic, proteomic, environmental, clinical and paraclinical) to increase the number of clinically validated biomarkers in order to identify patients in early stage even before the prediabetic phase. SIGNIFICANCE: In this paper, we discuss the epidemic dimension of metabolic disorders like type 2 diabetes mellitus (DM2) and the urgent demand for novel biomarkers to reduce the incidence or even delay the onset of DM2. Recent research data produced by "multi-omics" technologies (genomics/epigenomics, transcriptomics, proteomics and metabolomics), suggest that many potential biomarkers might be helpful in the prediction and early diagnosis of DM2. Predictive, Preventive and Personalized Medicine (PPPM) manages and integrates these data to apply personalized, preventive, and therapeutic approaches. This is significant because there is an emerging need for establishing channels for communication and personalized consultation between systems research and precision medicine, as the medicine of the future. PMID: 29518575 [PubMed - as supplied by publisher]

Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease. Genet Med. 2018 Mar 08;: Authors: Boczonadi V, King MS, Smith AC, Olahova M, Bansagi B, Roos A, Eyassu F, Borchers C, Ramesh V, Lochmüller H, Polvikoski T, Whittaker RG, Pyle A, Griffin H, Taylor RW, Chinnery PF, Robinson AJ, Kunji ERS, Horvath R Abstract PurposeTo understand the role of the mitochondrial oxodicarboxylate carrier (SLC25A21) in the development of spinal muscular atrophy-like disease.MethodsWe identified a novel pathogenic variant in a patient by whole-exome sequencing. The pathogenicity of the mutation was studied by transport assays, computer modeling, followed by targeted metabolic testing and in vitro studies in human fibroblasts and neurons.ResultsThe patient carries a homozygous pathogenic variant c.695A>G; p.(Lys232Arg) in the SLC25A21 gene, encoding the mitochondrial oxodicarboxylate carrier, and developed spinal muscular atrophy and mitochondrial myopathy. Transport assays show that the mutation renders SLC25A21 dysfunctional and 2-oxoadipate cannot be imported into the mitochondrial matrix. Computer models of central metabolism predicted that impaired transport of oxodicarboxylate disrupts the pathways of lysine and tryptophan degradation, and causes accumulation of 2-oxoadipate, pipecolic acid, and quinolinic acid, which was confirmed in the patient's urine by targeted metabolomics. Exposure to 2-oxoadipate and quinolinic acid decreased the level of mitochondrial complexes in neuronal cells (SH-SY5Y) and induced apoptosis.ConclusionMitochondrial oxodicarboxylate carrier deficiency leads to mitochondrial dysfunction and the accumulation of oxoadipate and quinolinic acid, which in turn cause toxicity in spinal motor neurons leading to spinal muscular atrophy-like disease.GENETICS in MEDICINE advance online publication, 8 March 2018; doi:10.1038/gim.2017.251. PMID: 29517768 [PubMed - as supplied by publisher]

Related Articles The crucial role of multiomic approach in cancer research and clinically relevant outcomes. EPMA J. 2018 Mar;9(1):77-102 Authors: Lu M, Zhan X Abstract Cancer with heavily economic and social burden is the hot point in the field of medical research. Some remarkable achievements have been made; however, the exact mechanisms of tumor initiation and development remain unclear. Cancer is a complex, whole-body disease that involves multiple abnormalities in the levels of DNA, RNA, protein, metabolite and medical imaging. Biological omics including genomics, transcriptomics, proteomics, metabolomics and radiomics aims to systematically understand carcinogenesis in different biological levels, which is driving the shift of cancer research paradigm from single parameter model to multi-parameter systematical model. The rapid development of various omics technologies is driving one to conveniently get multi-omics data, which accelerates predictive, preventive and personalized medicine (PPPM) practice allowing prediction of response with substantially increased accuracy, stratification of particular patients and eventual personalization of medicine. This review article describes the methodology, advances, and clinically relevant outcomes of different "omics" technologies in cancer research, and especially emphasizes the importance and scientific merit of integrating multi-omics in cancer research and clinically relevant outcomes. PMID: 29515689 [PubMed]

Related Articles Growth of Malignant Non-CNS Tumors Alters Brain Metabolome. Front Genet. 2018;9:41 Authors: Kovalchuk A, Nersisyan L, Mandal R, Wishart D, Mancini M, Sidransky D, Kolb B, Kovalchuk O Abstract Cancer survivors experience numerous treatment side effects that negatively affect their quality of life. Cognitive side effects are especially insidious, as they affect memory, cognition, and learning. Neurocognitive deficits occur prior to cancer treatment, arising even before cancer diagnosis, and we refer to them as "tumor brain." Metabolomics is a new area of research that focuses on metabolome profiles and provides important mechanistic insights into various human diseases, including cancer, neurodegenerative diseases, and aging. Many neurological diseases and conditions affect metabolic processes in the brain. However, the tumor brain metabolome has never been analyzed. In our study we used direct flow injection/mass spectrometry (DI-MS) analysis to establish the effects of the growth of lung cancer, pancreatic cancer, and sarcoma on the brain metabolome of TumorGraft™ mice. We found that the growth of malignant non-CNS tumors impacted metabolic processes in the brain, affecting protein biosynthesis, and amino acid and sphingolipid metabolism. The observed metabolic changes were similar to those reported for neurodegenerative diseases and brain aging, and may have potential mechanistic value for future analysis of the tumor brain phenomenon. PMID: 29515623 [PubMed]

Related Articles Massive aggrecan and versican accumulation in thoracic aortic aneurysm and dissection. JCI Insight. 2018 Mar 08;3(5): Authors: Cikach FS, Koch CD, Mead TJ, Galatioto J, Willard BB, Emerton KB, Eagleton MJ, Blackstone EH, Ramirez F, Roselli EE, Apte SS Abstract Proteoglycan accumulation is a hallmark of medial degeneration in thoracic aortic aneurysm and dissection (TAAD). Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome. The aortic proteoglycanome comprises 20 proteoglycans including aggrecan and versican. Antibodies against these proteoglycans intensely stained medial degeneration lesions in TAAD, contrasting with modest intralamellar staining in controls. Aggrecan, but not versican, was increased in longitudinal analysis of Fbn1mgR/mgR aortas. TAAD and Fbn1mgR/mgR aortas had increased aggrecan and versican mRNAs, and reduced expression of a key proteoglycanase gene, ADAMTS5, was seen in TAAD. Fbn1mgR/mgR mice with ascending aortic dissection and/or rupture had dramatically increased aggrecan staining compared with mice without these complications. Thus, aggrecan and versican accumulation in ascending TAAD occurs via increased synthesis and/or reduced proteolytic turnover, and correlates with aortic dissection/rupture in Fbn1mgR/mgR mice. Tissue swelling imposed by aggrecan and versican is proposed to be profoundly deleterious to aortic wall mechanics and smooth muscle cell homeostasis, predisposing to type-A dissections. These proteoglycans provide potential biomarkers for refined risk stratification and timing of elective aortic aneurysm repair. PMID: 29515038 [PubMed - as supplied by publisher]

Related Articles Liver Metabolic Perturbations of Heat-Stressed Lactating Dairy Cows. Asian-Australas J Anim Sci. 2018 Mar 02;: Authors: Fan C, Su D, Tian H, Li X, Li Y, Ran L, Hu R, Cheng J Abstract Objective: The objective of the present study was to elucidate the mechanism underlying liver metabolic perturbations in dairy cows exposed to heat stress (HS). Method: Liquid chromatography mass spectrometry (LC-MS) was used to analyze metabolic differences in livers of 20 dairy cows, with and without exposure to HS. Results: The results revealed 33 potential metabolite candidate biomarkers for the detection of HS in dairy cows. Fifteen of these metabolites (glucose, lactate, pyruvate, acetoacetate, β-hydroxybutyrate (BHBA), fumaric acid, citric acid, choline, glycine, proline, isoleucine, leucine, urea, creatinine, and orotic acid) were previously found to be potential biomarkers of HS in plasma or milk, discriminating dairy cows with and without HS. Conclusion: All the potential diagnostic biomarkers were involved in glycolysis, amino acid, ketone, tricarboxylic acid (TCA), or nucleotide metabolism, indicating that HS mainly affected energy and nucleotide metabolism in lactating dairy cows. PMID: 29514433 [PubMed - as supplied by publisher]

Related Articles Mass spectrometry in epidemiological studies: What are the key considerations? Eur J Epidemiol. 2016 08;31(8):715-6 Authors: Dehghan A PMID: 27565981 [PubMed - indexed for MEDLINE]

Related Articles Transcriptome and metabolome of synthetic Solanum autotetraploids reveal key genomic stress events following polyploidization. New Phytol. 2016 Jun;210(4):1382-94 Authors: Fasano C, Diretto G, Aversano R, D'Agostino N, Di Matteo A, Frusciante L, Giuliano G, Carputo D Abstract Polyploids are generally classified as autopolyploids, derived from a single species, and allopolyploids, arising from interspecific hybridization. The former represent ideal materials with which to study the consequences of genome doubling and ascertain whether there are molecular and functional rules operating following polyploidization events. To investigate whether the effects of autopolyploidization are common to different species, or if species-specific or stochastic events are prevalent, we performed a comprehensive transcriptomic and metabolomic characterization of diploids and autotetraploids of Solanum commersonii and Solanum bulbocastanum. Autopolyploidization remodelled the transcriptome and the metabolome of both species. In S. commersonii, differentially expressed genes (DEGs) were highly enriched in pericentromeric regions. Most changes were stochastic, suggesting a strong genotypic response. However, a set of robustly regulated transcripts and metabolites was also detected, including purine bases and nucleosides, which are likely to underlie a common response to polyploidization. We hypothesize that autopolyploidization results in nucleotide pool imbalance, which in turn triggers a genomic shock responsible for the stochastic events observed. The more extensive genomic stress and the higher number of stochastic events observed in S. commersonii with respect to S. bulbocastanum could be the result of the higher nucleoside depletion observed in this species. PMID: 26915816 [PubMed - indexed for MEDLINE]

DNA distribution pattern and metabolite profile of wild edible lobster mushroom (Hypomyces lactifluorum/Russula brevipes). Genome. 2018 Mar 07;: Authors: Laperriere G, Desgagné-Penix I, Germain H Abstract Lobster mushroom is a wild edible mushroom with potential commercial value. It is the product resulting of the infection, most commonly of Russula brevipes by Hypomyces lactifluorum. This study undertook quantitative polymerase chain reaction analysis of tissues sampled at different infection stages, to investigate R. brevipes/H. lactifluorum interaction. We followed the colonization of R. brevipes sporocarps by H. lactifluorum which leads to the edible lobster mushrooms. In parallel, metabolomics analysis was performed to detect differences in metabolite profile among non-infected R. brevipes sporocarp and lobster mushroom. The results show that H. lactifluorum's DNA is not restricted to the margin, but is distributed relatively evenly across the sporocarp of the lobster mushroom. DNA of R. brevipes was also present throughout the sporocarp, but was less abundant at the margins and increased inwards. R. brevipes' DNA also declined as the infection progressed. Metabolomics analysis revealed that the flesh of lobster mushroom, which remains identical in appearance to the flesh of the host, undergoes transformation that alters its metabolite profile, most notably of lipids and terpene compounds. These results define a parasitic relationship between the two species which entails a decline of R. brevipes' DNA and a modification of its metabolite profile. PMID: 29514010 [PubMed - as supplied by publisher]

Augmented frontal cortex diacylglycerol levels in Parkinson's disease and Lewy Body Disease. PLoS One. 2018;13(3):e0191815 Authors: Wood PL, Tippireddy S, Feriante J, Woltjer RL Abstract BACKGROUND: Research from our laboratory, and that of other investigators, has demonstrated augmented levels of diacylglycerols (DAG) in the frontal cortex and plasma of subjects with Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). We have extended these observations to investigate the frontal cortex of subjects with Parkinson's disease (PD) and Lewy Body Disease (LBD), with and without coexisting pathologic features of AD. METHODS/PRINCIPAL FINDINGS: Utilizing a high-resolution mass spectrometry analytical platform, we clearly demonstrate that DAG levels are significantly increased in the frontal cortex of subjects with PD, LBD with intermediate neocortical AD neuropathology, and in LBD with established neocortical AD neuropathology. In the case of the PD cohort, increases in cortical DAG levels were detected in cases with no neocortical pathology but were greater in subjects with neocortical pathology. These data suggest that DAG changes occur early in the disease processes and are amplified as cortical dysfunction becomes more established. CONCLUSIONS: These findings suggest that altered DAG synthesis/metabolism is a common feature of neurodegenerative diseases, characterized by proteinopathy, that ultimately result in cognitive deficits. With regard to the mechanism responsible for these biochemical alterations, selective decrements in cortical levels of phosphatidylcholines in LBD and PD suggest that augmented degradation and/or decreased synthesis of these structural glycerophospholipids may contribute to increases in the pool size of free DAGs. The observed augmentation of DAG levels may be phospholipase-driven since neuroinflammation is a consistent feature of all disease cohorts. If this conclusion can be validated it would support utilizing DAG levels as a biomarker of the early disease process and the investigation of early intervention with anti-inflammatory agents. PMID: 29513680 [PubMed - in process]

Metabolic Profiling of Amino Acids Associated with Mortality in Patients with Acute Paraquat Poisoning. Med Sci Monit. 2018 Mar 07;24:1397-1407 Authors: Wan X, Zhou C, Kang X, Hu D, Xue W, Li X, Bao H, Peng A Abstract BACKGROUND Paraquat is a major cause of fatal poisoning after ingestion in many parts of Asia and the Pacific nations. However, optimal prognostic indicators to evaluate patient mortality have not been unequivocally established. Following acute paraquat poisoning, a number of amino acids (AA), are abnormally expressed in metabolic pathways. However, the alterations in AA metabolite levels after paraquat poisoning remain unknown in humans. MATERIAL AND METHODS In the present study, 40 patients were enrolled, of whom 16 survived and 24 died. A metabolomics approach was used to assess changes in AA metabolites in plasma and its potential prognostic value following paraquat poisoning. Mass spectrometry (MS) based on metabolite identification was conducted. RESULTS Twenty-five AA levels in plasma were abnormally expressed in non-survivor patients. Among them, creatinine, indolelactate, and 3-(4-hydroxyphenyl)lactate were found to be highly correlated with paraquat death prediction. It was noted that the intensity levels of these 3 AA metabolites in the non-survivor group were substantially higher than in the survivor group. Furthermore, we examined receiver operating characteristic (ROC) curves for clinical validation. ROC results showed that 3-(4-hydroxyphenyl)lactate had the highest AUC of 0.84, while indolelactate and creatinine had AUCs of 0.75 and 0.83, respectively, suggesting that they can be used to predict the clinical outcome (although this methodology is expensive to implement). CONCLUSIONS Metabolic profiling of AA levels could be a reliable tool to identify effective indicators for the early high precision prognosis of paraquat poisoning. PMID: 29513648 [PubMed - in process]

Integrating Proteomics and Targeted Metabolomics to Understand Global Changes in Histone Modifications. Proteomics. 2018 Mar 07;: Authors: Simithy J, Sidoli S, Garcia BA Abstract The chromatin fiber is the control panel of eukaryotic cells. Chromatin is mostly composed of DNA, which contains the genetic instruction for cell phenotype, and histone proteins, which provide the scaffold for chromatin folding and part of the epigenetic inheritance. Histone writers/erasers "flag" chromatin regions by catalyzing/removing covalent histone post-translational modifications (PTMs). Histone PTMs chemically contribute to chromatin relaxation or compaction and recruit histone readers to modulate DNA readout. The precursors of protein PTMs are mostly small metabolites. For instance, acetyl-CoA is used for acetylation, ATP for phosphorylation, and S-adenosyl methionine for methylation. Interestingly, PTMs such as acetylation can occur at neutral pH also without their respective enzyme when the precursor is sufficiently concentrated. Therefore, it is essential to differentially quantify the contribution of histone writers/erasers vs the effect of local concentration of metabolites to understand the primary regulation of histone PTM abundance. Aberrant phenotypes such as cancer cells have misregulated metabolism and thus the composition and the modulation of chromatin is not only driven by enzymatic tuning. In this review, we discuss the latest advances in mass spectrometry (MS) to analyze histone PTMs and the most adopted quantification methods for related metabolites, both necessary to understand PTM relative changes. This article is protected by copyright. All rights reserved. PMID: 29512899 [PubMed - as supplied by publisher]

Unbiased Lipidomics and Metabolomics of Human Brain Samples. Methods Mol Biol. 2018;1750:255-269 Authors: Astarita G, Stocchero M, Paglia G Abstract Mass spectrometry (MS)-based lipidomics and metabolomics approaches have been used to discover new diagnostic and therapeutic targets of neurodegenerative disorders. Here, we describe a protocol to conduct an integrated metabolomics and lipidomics profiling of postmortem brains of frozen tissue samples from clinically characterized patients and age-matched controls. Metabolites and lipids can be extracted from each brain tissue sample, using a biphasic liquid/liquid extraction method. An unbiased liquid chromatography MS-based lipidomics and metabolomics workflows allows to screen for the content and composition of lipids and polar metabolites for each brain tissue. Data processing and statistical analysis are then used to compare the molecular content of all the samples, grouping them into cluster based on molecular similarities. The final results highlight classes of metabolites and biochemical pathways that are altered in brain samples from diseased brains compared to those from healthy subjects, helping to generate novel hypotheses on their mechanistic and functional significance. PMID: 29512078 [PubMed - in process]

Mass Spectrometry-Based Metabolomic Multiplatform for Alzheimer's Disease Research. Methods Mol Biol. 2018;1750:125-137 Authors: González-Domínguez R, González-Domínguez Á, Sayago A, Fernández-Recamales Á Abstract The integration of complementary analytical platforms has emerged as a suitable strategy to perform a comprehensive metabolomic characterization of complex biological systems. In this work, we describe the most important issues to be considered for the application of a mass spectrometry multiplatform in Alzheimer's disease research, which combines direct analysis with electrospray and atmospheric pressure photoionization sources, as well as orthogonal hyphenated approaches based on reversed-phase ultrahigh-performance liquid chromatography and gas chromatography. These procedures have been optimized for the analysis of multiple biological samples from human patients and transgenic animal models, including blood serum, various brain regions (e.g., hippocampus, cortex, cerebellum, striatum, olfactory bulbs), and other peripheral organs (e.g., liver, kidney, spleen, thymus). It is noteworthy that the metabolomic pipeline here detailed has demonstrated a great potential for the investigation of metabolic perturbations underlying Alzheimer's disease pathogenesis. PMID: 29512069 [PubMed - in process]

CSF Lipidomics Analysis: High-Resolution Mass Spectrometry Analytical Platform. Methods Mol Biol. 2018;1750:69-74 Authors: Wood PL, Woltjer RL Abstract High-resolution mass spectrometry provides the resolution required for direct infusion allowing detection and characterization of a vast array of lipids with a single injection. This chapter presents the methodology utilized for both unbiased and targeted lipidomics of cerebrospinal fluid. PMID: 29512065 [PubMed - in process]

Epidemiology of Dementia: The Burden on Society, the Challenges for Research. Methods Mol Biol. 2018;1750:3-14 Authors: Wolters FJ, Arfan Ikram M Abstract Dementia is among the leading causes of death and disability. Due to the ageing population, its prevalence is expected to nearly triple worldwide by 2050, urging the development of preventive and curative interventions. Various modifiable risk factors have been identified in community-based cohort studies, but insight into the underlying pathophysiological mechanisms is lacking. Clinical trials have thus far failed in the development of disease-modifying therapy in patients with dementia, thereby triggering a shift of focus toward the presymptomatic phase of disease. The extensive preclinical disease course of Alzheimer's disease warrants reliable, easily obtainable biomarkers to aid in timely application of preventive strategies, selecting participants for neuroprotective trials, and disease monitoring in trials and clinical practice. Biomarker and drug discovery may yield the fruits from technology-driven developments in the field of genomics, epigenetics, metabolomics, and brain imaging. In that context, bridging the gap between translational and population research may well prove a giant leap toward development of successful preventive and curative interventions against dementia. PMID: 29512062 [PubMed - in process]

PROM and Labour Effects on Urinary Metabolome: A Pilot Study. Dis Markers. 2018;2018:1042479 Authors: Meloni A, Palmas F, Barberini L, Mereu R, Deiana SF, Fais MF, Noto A, Fattuoni C, Mussap M, Ragusa A, Dessì A, Pintus R, Fanos V, Melis GB Abstract Since pathologies and complications occurring during pregnancy and/or during labour may cause adverse outcomes for both newborns and mothers, there is a growing interest in metabolomic applications on pregnancy investigation. In fact, metabolomics has proved to be an efficient strategy for the description of several perinatal conditions. In particular, this study focuses on premature rupture of membranes (PROM) in pregnancy at term. For this project, urine samples were collected at three different clinical conditions: out of labour before PROM occurrence (Ph1), out of labour with PROM (Ph2), and during labour with PROM (Ph3). GC-MS analysis, followed by univariate and multivariate statistical analysis, was able to discriminate among the different classes, highlighting the metabolites most involved in the discrimination. PMID: 29511388 [PubMed - in process]