PubMed

MALDI imaging for the localization of saponins in root tissues and rapid differentiation of three Panax herbs. Electrophoresis. 2016 Mar 16; Authors: Wang S, Bai H, Cai Z, Gao D, Jiang Y, Liu J, Liu H Abstract The roots of Panax genus with ginseng saponins as bioactive ingredients have been widely used as herbal medicines and food additives. Panax ginseng, Panax quinquefolius and Panax notoginseng are three major commercial species in Panax genus, with similar morphological appearance but different pharmacological functions. Various methods have been developed and applied for the differentiation of these species. In this work, MALDI-TOF-mass spectrometry imaging (MSI) was employed for the localization of saponins in root tissues and for the rapid differentiation of the three Panax species for the first time. After a simple sample preparation, MALDI-TOF-MSI analysis of root tissue allowed the detection of 51 saponins. Localization of saponins in the tissue were mapped in ion images, which were obviously related to botanical structure. The localization modes varied with Panax species, providing valuable information for the discrimination of ginseng species. Principal component analysis (PCA) of data collected from areas with abundant saponins based on ion images was applied for the differentiation. Nine characteristic saponin peaks were identified from the PCA analysis. The MALDI-TOF-MSI together with area-specific data analysis provided high potential for the rapid differentiation of Panax herbs. This article is protected by copyright. All rights reserved. PMID: 26990111 [PubMed - as supplied by publisher]

Mechanism of Xinfeng Capsule on Adjuvant-Induced Arthritis via Analysis of Urinary Metabolomic Profiles. Autoimmune Dis. 2016;2016:5690935 Authors: Jiang H, Liu J, Wang T, Gao JR, Sun Y, Huang CB, Meng M, Qin XJ Abstract We aimed to explore the potential effects of Xinfeng capsule (XFC) on urine metabolic profiling in adjuvant-induced arthritis (AA) rats by using gas chromatography time-of-flight mass spectrometry (GC-TOF/MS). GC-TOF/MS technology was combined with multivariate statistical approaches, such as principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal projections to latent structures discriminant analysis (OPLS-DA). These methods were used to distinguish the healthy group, untreated group, and XFC treated group and elucidate potential biomarkers. Nine potential biomarkers such as hippuric acid, adenine, and L-dopa were identified as potential biomarkers, indicating that purine metabolism, fat metabolism, amino acid metabolism, and energy metabolism were disturbed in AA rats. This study demonstrated that XFC is efficacious for RA and explained its potential metabolomics mechanism. PMID: 26989506 [PubMed]

Sebaceous lipids are essential for water repulsion, protection against UVB-induced apoptosis, and ocular integrity in mice. Development. 2016 Mar 17; Authors: Dahlhoff M, Camera E, Schäfer M, Emrich D, Riethmacher D, Foster A, Paus R, Schneider MR Abstract Sebocytes, cells characterized by lipid accumulation leading to cell disruption, can be found in hair follicle-associated sebaceous glands (SGs) or in free SGs such as the Meibomian glands in the eyelids. Because genetic tools allowing sebocyte targeting while maintaining intact epidermal lipids are lacking, the relevance of sebaceous lipids in health and disease remains poorly understood. Using Scd3, a gene expressed exclusively in mature sebocytes, we established a mouse line with sebocyte-specific expression of cre recombinase. Both RT-PCR analysis and crossing into Rosa26-LacZ reporter mice and Kras(G12D) mice confirmed cre activity specifically in SGs, with no activity in other skin compartments. Importantly, loss of SCD3 function did not cause detectable phenotypical alterations, endorsing the usefulness of Scd3cre mice for further functional studies. Scd3cre-induced, diphtheria chain A toxin-mediated depletion of sebaceous lipids resulted in impaired water repulsion and thermoregulation, increased rates of UVB-induced epidermal apoptosis, and caused a severe pathology of the ocular surface resembling Meibomian gland dysfunction. This novel mouse line will be useful for further investigating the roles of sebaceous lipids in skin and eye integrity. PMID: 26989175 [PubMed - as supplied by publisher]

To treat or not to treat: metabolomics reveals biomarkers for treatment indication in chronic lymphocytic leukaemia patients. Oncotarget. 2016 Mar 14; Authors: Piszcz J, Armitage EG, Ferrarini A, Rupérez FJ, Kulczynska A, Bolkun L, Kloczko J, Kretowski A, Urbanowicz A, Ciborowski M, Barbas C Abstract In chronic lymphocytic leukaemia (CLL), the clinical course of patients is heterogeneous. Some present an aggressive disease onset and require immediate therapy, while others remain without treatment for years. Current disease staging systems developed by Rai and Binet may be useful in forecasting patient survival time, but do not discriminate between stable and progressive forms of the disease in the early stages. Recently ample attention has been directed towards identifying new disease prognostic markers capable of predicting clinical aggressiveness at diagnosis. In the present study serum samples from stable (n = 51) and progressive (n = 42) CLL patients and controls (n = 45) were used with aim to discover metabolic indicators of disease status. First an LC-MS based metabolic fingerprinting method was used to analyse selected samples in order to find a potential markers discriminating aggressive from indolent patients. Ten of these discovered markers were validated on the whole set of samples with an independent analytical technique. Linoleamide (p = 0.002) in addition to various acylcarnitines (p = 0.001-0.000001) showed to be significant markers of CLL in its aggressive form. Acetylcarnitine (p = 0.05) and hexannoylcarnitine (p = 0.005) were also distinguishable markers of indolent subjects. Forming a panel of selected acylcarnitines and fatty acid amides, it was possible to reach a potentially highly specific and sensitive diagnostic approach (AUC = 0.766). PMID: 26988915 [PubMed - as supplied by publisher]

Whole-body fat oxidation increases more by prior exercise than overnight fasting in elite endurance athletes. Appl Physiol Nutr Metab. 2015 Dec 17;:1-8 Authors: Andersson Hall U, Edin F, Pedersen A, Madsen K Abstract The purpose of this study was to compare whole-body fat oxidation kinetics after prior exercise with overnight fasting in elite endurance athletes. Thirteen highly trained athletes (9 men and 4 women; maximal oxygen uptake: 66 ± 1 mL·min(-1)·kg(-1)) performed 3 identical submaximal incremental tests on a cycle ergometer using a cross-over design. A control test (CON) was performed 3 h after a standardized breakfast, a fasting test (FAST) 12 h after a standardized evening meal, and a postexercise test (EXER) after standardized breakfast, endurance exercise, and 2 h fasting recovery. The test consisted of 3 min each at 30%, 40%, 50%, 60%, 70%, and 80% of maximal oxygen uptake and fat oxidation rates were measured through indirect calorimetry. During CON, maximal fat oxidation rate was 0.51 ± 0.04 g·min(-1) compared with 0.69 ± 0.04 g·min(-1) in FAST (P < 0.01), and 0.89 ± 0.05 g·min(-1) in EXER (P < 0.01). Across all intensities, EXER was significantly higher than FAST and FAST was higher than CON (P < 0.01). Blood insulin levels were lower and free fatty acid and cortisol levels were higher at the start of EXER compared with CON and FAST (P < 0.05). Plasma nuclear magnetic resonance-metabolomics showed similar changes in both EXER and FAST, including increased levels of fatty acids and succinate. In conclusion, prior exercise significantly increases whole-body fat oxidation during submaximal exercise compared with overnight fasting. Already high rates of maximal fat oxidation in elite endurance athletes were increased by approximately 75% after prior exercise and fasting recovery. PMID: 26988766 [PubMed - as supplied by publisher]

Introduction to metabolomics and its applications in ophthalmology. Eye (Lond). 2016 Mar 18; Authors: Tan SZ, Begley P, Mullard G, Hollywood KA, Bishop PN Abstract Metabolomics is the study of endogenous and exogenous metabolites in biological systems, which aims to provide comparative semi-quantitative information about all metabolites in the system. Metabolomics is an emerging and potentially powerful tool in ophthalmology research. It is therefore important for health professionals and researchers involved in the speciality to understand the basic principles of metabolomics experiments. This article provides an overview of the experimental workflow and examples of its use in ophthalmology research from the study of disease metabolism and pathogenesis to identification of biomarkers.Eye advance online publication, 18 March 2016; doi:10.1038/eye.2016.37. PMID: 26987591 [PubMed - as supplied by publisher]

Metabolomics in Breast Cancer: Current Status and Perspectives. Adv Exp Med Biol. 2016;882:217-34 Authors: Hart CD, Tenori L, Luchinat C, Di Leo A Abstract Metabolomics refers to the study of the whole set of metabolites in a biological sample that constitute a reflection of cellular functions. Cancer cells display significantly altered cellular processes, and thus metabolites, compared to normal cells. This can be detected in a number of ways, and is already exploited to a limited extent in the diagnosis of cancer. The host response to the tumor is perhaps equally important, as it either rejects or permits tumor growth, and this may also potentially result in a measurable metabolite signature. Analysis then of entire pools of metabolites may yield critical information about both tumor presence and host response, and represent a possible novel collective biomarker for cancer behaviour that could allow prediction of relapse, response to therapy, or progression. Isolating meaningful differences in the sea of metabolites and within the context of significant metabolic heterogeneity both within and between patients remains a great challenge. This chapter will review current metabolomic research in breast cancer, with a focus on efforts to translate the technology into clinical practice. PMID: 26987537 [PubMed - in process]

Related Articles Integration of microfluidic LC with HRMS for the analysis of analytes in biofluids: past, present and future. Bioanalysis. 2015;7(11):1397-411 Authors: Rainville PD, Langridge JI, Wrona MD, Wilson ID, Plumb RS Abstract Capillary LC (cLC) coupled to MS has the potential to improve detection limits, address limited sample volumes and allow multiple analyses from one sample. This is particularly attractive in areas where ultrahigh assay sensitivity, low limits of detection and small sample volumes are becoming commonplace. However, implementation of cLC-MS in the bioanalytical-drug metabolism area had been hampered by the lack of commercial instrumentation and the need for experts to operate the system. Recent advances in microfabricated devices such as chip-cube and ion-key technologies offer the potential for true implementation of cLC in the modern laboratory including the benefits of the combination of this type of separation with high-resolution MS. PMID: 26110713 [PubMed - indexed for MEDLINE]

Sexual Dimorphism in Activation of Placental Autophagy in Obese Women with Evidence for Fetal Programming from a Placenta-Specific Mouse Model. Autophagy. 2016 Mar 17;:0 Authors: Muralimanoharan S, Gao X, Weintraub S, Myatt L, Maloyan A Abstract The incidence of maternal obesity and its co-morbidities (diabetes, cardiovascular disease) continues to increase at an alarming rate, with major public health implications. In utero exposure to maternal obesity has been associated with development of cardiovascular and metabolic diseases in the offspring as a result of developmental programming. The placenta regulates maternal-fetal metabolism and shows significant changes in its function with maternal obesity. Autophagy is a cell survival process, which is responsible for the degradation of damaged organelles and misfolded proteins. Here we show an activation of autophagosomal formation and autophagosome-lysosome fusion in placentas of males but not females from overweight (OW) and obese (OB) women vs. normal weight (NW) women. However, total autophagic activity in these placentas appeared to be decreased as it showed an increase in SQSTM1/p62 and a decrease in lysosomal biogenesis. A mouse model with a targeted deletion of the essential autophagy gene Atg7 in placental tissue showed significant placental abnormalities comparable to those seen in human placenta with maternal obesity. These included a decrease in expression of mitochondrial genes and antioxidants, and decreased lysosomal biogenesis. Strikingly, the knockout mice were developmentally programmed as they showed an increased sensitivity to high-fat diet-induced obesity, hyperglycemia, hyperinsulinemia, increased adiposity, and cardiac remodeling. In summary, our results indicate a sexual dimorphism in placental autophagy in response to maternal obesity. We also show that autophagy plays an important role in placental function and that inhibition of placental autophagy programs the offspring to obesity, and to metabolic and cardiovascular diseases. PMID: 26986453 [PubMed - as supplied by publisher]

A hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) based metabolomics study on colour stability of ovine meat. Meat Sci. 2016 Feb 20;117:163-172 Authors: Subbaraj AK, Kim YH, Fraser K, Farouk MM Abstract Meat colour is one of the cues available to the consumer to gauge overall meat quality and wholesomeness. Colour stability of meat is determined by several factors both inherent to the animal and post-slaughter conditions, including ageing, storage/packaging and display times. A hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) based metabolomics study was undertaken to identify and compare polar metabolites between ovine meat samples that were exposed to different durations of ageing, storage conditions, and display times. Primary metabolites comprising amino acids, sugars, nucleotides, nucleosides, organic acids and their breakdown products were mainly identified as discriminating factors. For the first time, boron complexes of sugar and malic acid were also tentatively identified. As expected, most compounds identified were related to myoglobin chemistry, and compounds with antioxidant properties were found in higher levels in colour stable samples. Supplementary studies identifying semi-polar, non-polar and volatile compounds will provide a holistic understanding of the chemical basis of colour stability in ovine meat. PMID: 26986230 [PubMed - as supplied by publisher]

Uptake of caprolactam and its influence on growth and oxygen production of Desmodesmus quadricauda algae. Environ Pollut. 2016 Mar 14;213:518-523 Authors: Kalinová JP, Tříska J, Vrchotová N, Novák J Abstract The consumption of polyamides produced from caprolactam is increasing continuously, and for that reason the danger of environmental contamination by this lactam is also rising. This study's aim was to evaluate the influence of caprolactam on the growth and oxygen production of the green alga Desmodesmus quadricauda and on caprolactam uptake by this alga. The presence of caprolactam in water was observed to cause the algae significantly to increase its oxygen production. Caprolactam concentration of 5,000 mg/L stopped algae growth after 6 days and influenced coenobia structure (seen as disappearance of pyrenoids, deformation of cells) but did not decrease the number of cells in the coenobia. Caprolactam uptake is probably passive but relatively rapid. Maximum concentration in the algae was reached after 18-24 h. PMID: 26985739 [PubMed - as supplied by publisher]

Association of Plasma Small-Molecule Intermediate Metabolites With Age and Body Mass Index Across Six Diverse Study Populations. J Gerontol A Biol Sci Med Sci. 2016 Mar 16; Authors: Kraus WE, Pieper CF, Huffman KM, Thompson DK, Kraus VB, Morey MC, Cohen HJ, Ravussin E, Redman LM, Bain JR, Stevens RD, Newgard CB Abstract BACKGROUND: Older age and obesity are associated with metabolic dysregulation; the mechanism by which these factors impact metabolism across the lifespan is important, but relatively unknown. We evaluated a panel of amino acids (AAs) and acylcarnitines (ACs) to identify effects of age and adiposity (body mass index) on circulating small-molecule metabolites in a meta-analysis of six diverse study populations. METHODS: Targeted metabolic profiling was performed in six independent studies, representing 739 subjects with a broad range of age, body mass index, health states, and ethnic origin. Principal components analysis was performed on log-normalized values for AAs and ACs separately, generating one AC factor and two AA factors for each study. A common AC factor consisted primarily of acetylcarnitine, medium-chain AC, and several long-chain AC. AA Factor 1 consisted primarily of large neutral AAs. Glycine was its own factor. RESULTS: Metabolic profiling and factor analysis identified clusters of related metabolites of lipid and AA metabolism that were consistently associated with age and body mass in a series of studies with a broad range of age, body mass index, and health status. An inverse association of glycine with body mass index and male gender supports its role as a marker of favorable metabolic health. CONCLUSIONS: An important focus of future investigations should be to determine whether these clusters of metabolic intermediates are possible early predictors of health outcomes associated with body mass; are involved with accelerated aging; are involved in the causative pathway of aging; and how modification of these metabolic pathways impact the biology of aging. PMID: 26984390 [PubMed - as supplied by publisher]

NMR- and GC/MS-based metabolomics of sulfur mustard exposed individuals: a pilot study. Biomarkers. 2016 Mar 17;:1-11 Authors: Nobakht BF, Aliannejad R, Rezaei-Tavirani M, Arefi Oskouie A, Naseri MT, Parastar H, Aliakbarzadeh G, Fathi F, Taheri S Abstract Sulfur mustard (SM) is a potent alkylating agent and its effects on cells and tissues are varied and complex. Due to limitations in the diagnostics of sulfur mustard exposed individuals (SMEIs) by noninvasive approaches, there is a great necessity to develop novel techniques and biomarkers for this condition. We present here the first nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC/MS) metabolic profiling of serum from and healthy controls to identify novel biomarkers in blood serum for better diagnostics. Of note, SMEIs were exposed to SM 30 years ago and that differences between two groups could still be found. Pathways in which differences between SMEIs and healthy controls are observed are related to lipid metabolism, ketogenesis, tricarboxylic acid (TCA) cycle and amino acid metabolism. PMID: 26984270 [PubMed - as supplied by publisher]

Related Articles SIMAT: GC-SIM-MS data analysis tool. BMC Bioinformatics. 2015;16:259 Authors: Ranjbar MR, Di Poto C, Wang Y, Ressom HW Abstract BACKGROUND: Gas chromatography coupled with mass spectrometry (GC-MS) is one of the technologies widely used for qualitative and quantitative analysis of small molecules. In particular, GC coupled to single quadrupole MS can be utilized for targeted analysis by selected ion monitoring (SIM). However, to our knowledge, there are no software tools specifically designed for analysis of GC-SIM-MS data. In this paper, we introduce a new R/Bioconductor package called SIMAT for quantitative analysis of the levels of targeted analytes. SIMAT provides guidance in choosing fragments for a list of targets. This is accomplished through an optimization algorithm that has the capability to select the most appropriate fragments from overlapping chromatographic peaks based on a pre-specified library of background analytes. The tool also allows visualization of the total ion chromatograms (TIC) of runs and extracted ion chromatograms (EIC) of analytes of interest. Moreover, retention index (RI) calibration can be performed and raw GC-SIM-MS data can be imported in netCDF or NIST mass spectral library (MSL) formats. RESULTS: We evaluated the performance of SIMAT using two GC-SIM-MS datasets obtained by targeted analysis of: (1) plasma samples from 86 patients in a targeted metabolomic experiment; and (2) mixtures of internal standards spiked in plasma samples at varying concentrations in a method development study. Our results demonstrate that SIMAT offers alternative solutions to AMDIS and MetaboliteDetector to achieve accurate detection of targets and estimation of their relative intensities by analysis of GC-SIM-MS data. CONCLUSIONS: We introduce a new R package called SIMAT that allows the selection of the optimal set of fragments and retention time windows for target analytes in GC-SIM-MS based analysis. Also, various functions and algorithms are implemented in the tool to: (1) read and import raw data and spectral libraries; (2) perform GC-SIM-MS data preprocessing; and (3) plot and visualize EICs and TICs. PMID: 26283310 [PubMed - indexed for MEDLINE]

Related Articles Severe disturbance of glucose metabolism in peripheral blood mononuclear cells of schizophrenia patients: a targeted metabolomic study. J Transl Med. 2015;13:226 Authors: Liu ML, Zhang XT, Du XY, Fang Z, Liu Z, Xu Y, Zheng P, Xu XJ, Cheng PF, Huang T, Bai SJ, Zhao LB, Qi ZG, Shao WH, Xie P Abstract BACKGROUND: Schizophrenia is a widespread and debilitating mental disorder. However, the underlying molecular mechanism of schizophrenia remains largely unknown and no objective laboratory tests are available to diagnose this disorder. The aim of the present study was to characterize the alternations of glucose metabolites and identify potential diagnostic biomarkers for schizophrenia. METHODS: Gas chromatography/mass spectrometry based targeted metabolomic method was used to quantify the levels of 13 glucose metabolites in peripheral blood mononuclear cells (PBMCs) derived from healthy controls, schizophrenia and major depression subjects (n = 55 for each group). RESULTS: The majority (84.6%) of glucose metabolites were significantly disturbed in schizophrenia subjects, while only two (15.4%) glucose metabolites were differently expressed in depression subjects relative to healthy controls in both training set (n = 35/group) and test set (n = 20/group). Antipsychotics had only a subtle effect on glucose metabolism pathway. Moreover, ribose 5-phosphate in PBMCs showed a high diagnostic performance for first-episode drug-naïve schizophrenia subjects. CONCLUSION: These findings suggested disturbance of glucose metabolism may be implicated in onset of schizophrenia and could aid in development of diagnostic tool for this disorder. PMID: 26169624 [PubMed - indexed for MEDLINE]

Related Articles The effects of size and surface modification of amorphous silica particles on biodistribution and liver metabolism in mice. Nanotechnology. 2015 May 1;26(17):175101 Authors: Lu X, Ji C, Jin T, Fan X Abstract Engineered nanoparticles, with unconventional properties, are promising platforms for biomedical applications. Since they may interact with a wide variety of biomolecules, it is critical to understand the impact of the physicochemical properties of engineered nanoparticles on biological systems. In this study, the effects of particle size and surface modification alone or in combination of amorphous silica particles (SPs) on biological responses were determined using a suite of general toxicological assessments and metabonomics analysis in mice model. Our results suggested that amino or carboxyl surface modification mitigated the liver toxicity of plain-surface SPs. 30 nm SPs with amino surface modification were found to be the most toxic SPs among all the surface-modified SP treatments at the same dosage. When treatment dose was increased, submicro-sized SPs with amino or carboxyl surface modification also induced liver toxicity. Biodistribution studies suggested that 70 nm SPs were mainly accumulated in liver and spleen regardless of surface modifications. Interestingly, these two organs exhibited different uptake trends. Furthermore, metabonomics studies indicated that surface modification plays a more dominant role to affect the liver metabolism than particle size. PMID: 25837432 [PubMed - indexed for MEDLINE]

Related Articles Diagnosis and Monitoring of Cystinosis Using Immunomagnetically Purified Granulocytes. Clin Chem. 2016 Mar 15; Authors: Gertsman I, Johnson WS, Nishikawa C, Gangoiti JA, Holmes B, Barshop BA Abstract BACKGROUND: Cystine determination is a critical biochemical test for the diagnosis and therapeutic monitoring of the lysosomal storage disease cystinosis. The classical mixed-leukocyte cystine assay requires prompt specialized recovery/isolation following blood drawing, providing cystine concentrations normalized to total protein from assorted types of white blood cells, each with varying cystine content. METHODS: We present a new workflow for cystine determination using immunomagnetic granulocyte purification, and new reference ranges established form 47 patient and 27 obligate heterozygote samples assayed. Samples were collected in acid-citrate dextrose tubes and their stability was proven to allow for overnight shipping before analysis. Cystine was quantified by LC-MS/MS. RESULTS: The new method was reproducible (<15% root mean square error) and specific, assaying purified granulocytes from blood samples that no longer required immediate preparation and therefore allowing for up to 30 h before processing. There was a nearly a 2-fold increase in the therapeutic target (1.9 nmol half-cystine/mg protein) range, established using distributions of patient, obligate heterozygote, and control samples. The 2.5-97.5 percentile ranges (- 2 SD to + 2 SD around mean) for these cohorts were 0.67- 6.05 nmol/mg protein for patients, 0.33-1.35 nmol/mg protein for obligate heterozygotes, and 0.09-0.35 nmol/mg protein for controls. CONCLUSIONS: The intracellular cystine determination method using immunopurified granulocytes followed by LC-MS/MS analysis improves the inherent variability of mixed leukocyte analysis and eliminates the need for immediate sample preparation following blood draw. PMID: 26980209 [PubMed - as supplied by publisher]

Related Articles The Presence Of Lc3b Puncta And Hmgb1 Expression In Malignant Cells Correlate With The Immune Infiltrate In Breast Cancer. Autophagy. 2016 Mar 16;:0 Authors: Ladoire S, Enot D, Senovilla L, Ghiringhelli F, Poirier-Colame V, Chaba K, Semeraro M, Chaix M, Penault-Llorca F, Arnould L, Poillot ML, Arveux P, Delaloge S, Andre F, Zitvogel L, Kroemer G Abstract Several cell-intrinsic alterations have poor prognostic features in human breast cancer, as exemplified by the absence of MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta)-positive puncta in the cytoplasm (which indicates reduced autophagic flux) or the loss of nuclear HMGB1 expression by malignant cells. It is well established that breast cancer is under strong immunosurveillance, as reflected by the fact that scarce infiltration of the malignant lesion by CD8(+) cytotoxic T lymphocytes or comparatively dense infiltration by immunosuppressive cell types (such as FOXP3(+) regulatory T cells or CD68(+) tumor-associated macrophages), resulting in low CD8(+):FOXP3(+) or CD8(+):CD68(+) ratios, has a negative prognostic impact. Here, we reveal the surprising finding that cell-intrinsic features may influence the composition of the immune infiltrate in human breast cancer. Thus, the absence of LC3B puncta is correlated with intratumoral (but not peritumoral) infiltration by fewer CD8(+) cells and more FOXP3(+) or CD68(+) cells, resulting in a major drop in the CD8(+):FOXP3(+) or CD8(+):CD68(+) ratios. Moreover, absence of HMGB1 expression in nucleus correlated with a general drop in all immune effectors, in particular FOXP3(+) and CD68(+) cells, both within the tumor and close to it. Combined analysis of LC3B puncta and HMGB1 expression allowed for improved stratification of patients with respect to the characteristics of their immune infiltrate as well as overall and metastasis-free survival. It can be speculated that blocked autophagy in, or HMGB1 loss from, cancer cells may favor tumor progression due to their negative impact on anticancer immunosurveillance. PMID: 26979828 [PubMed - as supplied by publisher]

Related Articles Insights into mutualism mechanism and versatile metabolism of Ketogulonicigenium vulgare Hbe602 based on comparative genomics and metabolomics studies. Sci Rep. 2016;6:23068 Authors: Jia N, Ding MZ, Du J, Pan CH, Tian G, Lang JD, Fang JH, Gao F, Yuan YJ Abstract Ketogulonicigenium vulgare has been widely used in vitamin C two steps fermentation and requires companion strain for optimal growth. However, the understanding of K. vulgare as well as its companion strain is still preliminary. Here, the complete genome of K. vulgare Hbe602 was deciphered to provide insight into the symbiosis mechanism and the versatile metabolism. K. vulgare contains the LuxR family proteins, chemokine proteins, flagellar structure proteins, peptides and transporters for symbiosis consortium. Besides, the growth state and metabolite variation of K. vulgare were observed when five carbohydrates (D-sorbitol, L-sorbose, D-glucose, D-fructose and D-mannitol) were used as carbon source. The growth increased by 40.72% and 62.97% respectively when K. vulgare was cultured on D-mannitol/D-sorbitol than on L-sorbose. The insufficient metabolism of carbohydrates, amino acids and vitamins is the main reason for the slow growth of K. vulgare. The combined analysis of genomics and metabolomics indicated that TCA cycle, amino acid and nucleotide metabolism were significantly up-regulated when K. vulgare was cultured on the D-mannitol/D-sorbitol, which facilitated the better growth. The present study would be helpful to further understand its metabolic structure and guide the engineering transformation. PMID: 26979567 [PubMed - in process]

Related Articles Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol. 2016 Mar 16; Authors: Johnson CH, Ivanisevic J, Siuzdak G Abstract Metabolomics, which is the profiling of metabolites in biofluids, cells and tissues, is routinely applied as a tool for biomarker discovery. Owing to innovative developments in informatics and analytical technologies, and the integration of orthogonal biological approaches, it is now possible to expand metabolomic analyses to understand the systems-level effects of metabolites. Moreover, because of the inherent sensitivity of metabolomics, subtle alterations in biological pathways can be detected to provide insight into the mechanisms that underlie various physiological conditions and aberrant processes, including diseases. PMID: 26979502 [PubMed - as supplied by publisher]