PubMed

Related Articles Lipidomic-based investigation into the regulatory effect of Schisandrin B on palmitic acid level in non-alcoholic steatotic livers. Sci Rep. 2015;5:9114 Authors: Kwan HY, Niu X, Dai W, Tong T, Chao X, Su T, Chan CL, Lee KC, Fu X, Yi H, Yu H, Li T, Tse AK, Fong WF, Pan SY, Lu A, Yu ZL Abstract Schisandrin B (SchB) is one of the most abundant bioactive dibenzocyclooctadiene derivatives found in the fruit of Schisandra chinensis. Here, we investigated the potential therapeutic effects of SchB on non-alcoholic fatty-liver disease (NAFLD). In lipidomic study, ingenuity pathway analysis highlighted palmitate biosynthesis metabolic pathway in the liver samples of SchB-treated high-fat-diet-fed mice. Further experiments showed that the SchB treatment reduced expression and activity of fatty acid synthase, expressions of hepatic mature sterol regulatory element binding protein-1 and tumor necrosis factor-α, and hepatic level of palmitic acid which is known to promote progression of steatosis to steatohepatitis. Furthermore, the treatment also reduced hepatic fibrosis, activated nuclear factor-erythroid-2-related factor-2 which is known to attenuate the progression of NASH-related fibrosis. Interestingly, in fasting mice, a single high-dose SchB induced transient lipolysis and increased the expressions of adipose triglyceride lipase and phospho-hormone sensitive lipase. The treatment also increased plasma cholesterol levels and 3-hydroxy-3-methylglutaryl-CoA reductase activity, reduced the hepatic low-density-lipoprotein receptor expression in these mice. Our data not only suggest SchB is a potential therapeutic agent for NAFLD, but also provided important information for a safe consumption of SchB because SchB overdosed under fasting condition will have adverse effects on lipid metabolism. PMID: 25766252 [PubMed - indexed for MEDLINE]

Related Articles Quantitative metabolic imaging using endogenous fluorescence to detect stem cell differentiation. Sci Rep. 2013;3:3432 Authors: Quinn KP, Sridharan GV, Hayden RS, Kaplan DL, Lee K, Georgakoudi I Abstract The non-invasive high-resolution spatial mapping of cell metabolism within tissues could provide substantial advancements in assessing the efficacy of stem cell therapy and understanding tissue development. Here, using two-photon excited fluorescence microscopy, we elucidate the relationships among endogenous cell fluorescence, cell redox state, and the differentiation of human mesenchymal stem cells into adipogenic and osteoblastic lineages. Using liquid chromatography/mass spectrometry and quantitative PCR, we evaluate the sensitivity of an optical redox ratio of FAD/(NADH + FAD) to metabolic changes associated with stem cell differentiation. Furthermore, we probe the underlying physiological mechanisms, which relate a decrease in the redox ratio to the onset of differentiation. Because traditional assessments of stem cells and engineered tissues are destructive, time consuming, and logistically intensive, the development and validation of a non-invasive, label-free approach to defining the spatiotemporal patterns of cell differentiation can offer a powerful tool for rapid, high-content characterization of cell and tissue cultures. PMID: 24305550 [PubMed - indexed for MEDLINE]

19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2015/10/16PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Comparison of Fc N-Glycosylation of Pharmaceutical Products of Intravenous Immunoglobulin G. PLoS One. 2015;10(10):e0139828 Authors: Fokkink WJ, Falck D, Santbergen TC, Huizinga R, Wuhrer M, Jacobs BC Abstract Intravenous immunoglobulin (IVIg) products from different pharmaceutical companies vary in composition, in part because of the selected blood donors and production process. N-glycosylation of the Fc-portion of IgG varies between blood donors and may influence both the side-effects and therapeutic effectiveness of IVIg. At present, the variation in Fc N-glycosylation between IVIg products has not been defined. Utilizing mass spectrometry, we performed relative quantitation of the Fc N-glycosylation of IgG, assessing a total of 154 unique lot numbers of IVIg. Seven products showed comparable Fc N-glycosylation, with only one product differing from the others in all glycosylation features (galactosylation, sialylation, fucosylation and bisecting N-acetylglucosamine). However, the mean difference did not exceed 3%. Within product variation was present to a minor degree, but largely indistinguishable from analytical variation. In conclusion, we expect that the minor variation in Fc N-glycosylation between IVIg products has a small effect, if any, on the biological activity. PMID: 26457892 [PubMed - as supplied by publisher]

Influence of Different Drying Treatments and Extraction Solvents on the Metabolite Profile and Nitric Oxide Inhibitory Activity of Ajwa Dates. J Food Sci. 2015 Oct 12; Authors: Abdul-Hamid NA, Abas F, Ismail IS, Shaari K, Lajis NH Abstract This study aimed to examine the variation in the metabolite profiles and nitric oxide (NO) inhibitory activity of Ajwa dates that were subjected to 2 drying treatments and different extraction solvents. (1) H NMR coupled with multivariate data analysis was employed. A Griess assay was used to determine the inhibition of the production of NO in RAW 264.7 cells treated with LPS and interferon-γ. The oven dried (OD) samples demonstrated the absence of asparagine and ascorbic acid as compared to the freeze dried (FD) dates. The principal component analysis showed distinct clusters between the OD and FD dates by the second principal component. In respect of extraction solvents, chloroform extracts can be distinguished by the absence of arginine, glycine and asparagine compared to the methanol and 50% methanol extracts. The chloroform extracts can be clearly distinguished from the methanol and 50% methanol extracts by first principal component. Meanwhile, the loading score plot of partial least squares analysis suggested that beta glucose, alpha glucose, choline, ascorbic acid and glycine were among the metabolites that were contributing to higher biological activity displayed by FD and methanol extracts of Ajwa. The results highlight an alternative method of metabolomics approach for determination of the metabolites that contribute to NO inhibitory activity. PMID: 26457883 [PubMed - as supplied by publisher]

Bioanalytical derivatization: is there still room for development? Bioanalysis. 2015 Oct 12; Authors: Giera M PMID: 26457481 [PubMed - as supplied by publisher]

Rice-gall midge interactions: battle for survival. J Insect Physiol. 2015 Oct 8; Authors: Bentur JS, Rawat N, Divya D, Sinha DK, Agarrwal R, Atray I, Nair S Abstract Gall midges are insects specialized in maneuvering plant growth, metabolic and defense pathways for their benefit. The Asian rice gall midge and rice share such an intimate relationship that there is a constant battle for survival by either partner. Diverse responses by the rice host against the midge include necrotic hypersensitive resistance reaction, non-hypersensitive resistance reaction and gall-forming compatible interaction. Genetic studies have revealed that major R (resistance) genes confer resistance to gall midge in rice. Eleven gall midge R genes have been characterized so far in different rice varieties in India. In addition, no single R gene confers resistance against all the seven biotypes of the Asian rice gall midge, and none of the biotypes is virulent against all the resistance genes. Further, the interaction of the plant resistance gene with the insect avirulence gene is on a gene-for-gene basis. Our recent investigations involving suppressive subtraction hybridization cDNA libraries, microarray analyses, gene expression assays and metabolic profiling have revealed several molecular mechanisms, metabolite markers and pathways that are induced, down-regulated or altered in the rice host during incompatible or compatible interactions with the pest. This is also true for some of the pathways studied in the gall midge. Next generation sequencing technology, gene expression studies and conventional screening of gall midge cDNA libraries highlighted molecular approaches adopted by the insect to feed, survive and reproduce. This constant struggle by the midge to overcome the host defenses and the host to resist the pest has provided us with an opportunity to observe this battle for survival at the molecular level. PMID: 26455891 [PubMed - as supplied by publisher]

Related Articles A metabolomic study using HPLC-TOF/MS coupled with ingenuity pathway analysis: Intervention effects of Rhizoma Alismatis on spontaneous hypertensive rats. J Pharm Biomed Anal. 2015 Sep 25;117:446-452 Authors: Chu Y, Jiang H, Ju J, Li Y, Gong L, Wang X, Yang W, Deng Y Abstract Rhizoma Alismatis, an important crude herb component in traditional Chinese medicine, has been commonly used for treating hypertension, but its mechanism has not been clarified in level of metabolic. Therefore, in the present work, metabolomics study coupled with ingenuity pathway analysis (IPA) have been performed to explore the potential mechanism in anti-hypertensive effect of Rhizoma Alismatis. Serum samples from SHRs and WKYs were analyzed with the use of high performance liquid chromatography coupled with time of flight mass spectrometry detection (HPLC-TOF/MS) in positive polarity. The obtained data sets were statistically analyzed using univariate and multivariate statistical analyses including the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) for pattern recognition and selection of significant metabolites. 12 potential biomarkers in rat serum were screened out from HMDB, METLIN and KEGG databases. Furthermore, IPA was introduced and Glycerophospholipid metabolism and Purine metabolism were filtered out as potential target pathways. This metabolomic approach coupled with IPA provided a feasible way to understand the therapeutic mechanism of Rhizoma Alismatis on spontaneous hypertensive rats. PMID: 26454337 [PubMed - as supplied by publisher]

Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice. Biochem Biophys Res Commun. 2015 Oct 7; Authors: Geiger A, Walker A, Nissen E Abstract Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-β1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers. PMID: 26454169 [PubMed - as supplied by publisher]

Altered histamine neurotransmission in HPRT-deficient mice. Neurosci Lett. 2015 Oct 7; Authors: Tschirner SK, Gutzki F, Kaever V, Seifert R, Schneider EH Abstract Lesch-Nyhan syndrome (LNS) is an X-chromosomal disorder with congenital deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) as underlying defect. We determined the concentrations of dopamine, histamine and their metabolites in brains of HPRT knockout mice, which serve as an animal model for LNS, and compared the results to those obtained from wild-type controls. Analyses were performed by high performance liquid chromatography (HPLC)-coupled tandem mass spectrometry (MS/MS). Besides a decrease of dopamine and 3-methoxytyramine (3-MT) concentrations in the cerebral hemisphere, HPRT-deficient mice also exhibited significantly reduced 1-methyl histamine (1-MH) and 1-methylimidazole-4-acetic acid (1-MI4AA) concentrations in the brain hemisphere and medulla. Moreover, the amount of 1-MI4AA was significantly decreased in the cerebellum. Our findings show that neuronal perturbations caused by HPRT deficiency are not restricted to the dopamine system but also affect histaminergic neurotransmission. These new insights into the brain metabolism of an LNS mouse model may help to find new therapeutic strategies to improve the quality of life of LNS patients. PMID: 26453761 [PubMed - as supplied by publisher]

Dectin-1 Activation by a Natural Product β-Glucan Converts Immunosuppressive Macrophages into an M1-like Phenotype. J Immunol. 2015 Oct 9; Authors: Liu M, Luo F, Ding C, Albeituni S, Hu X, Ma Y, Cai Y, McNally L, Sanders MA, Jain D, Kloecker G, Bousamra M, Zhang HG, Higashi RM, Lane AN, Fan TW, Yan J Abstract Tumor-associated macrophages (TAM) with an alternatively activated phenotype have been linked to tumor-elicited inflammation, immunosuppression, and resistance to chemotherapies in cancer, thus representing an attractive target for an effective cancer immunotherapy. In this study, we demonstrate that particulate yeast-derived β-glucan, a natural polysaccharide compound, converts polarized alternatively activated macrophages or immunosuppressive TAM into a classically activated phenotype with potent immunostimulating activity. This process is associated with macrophage metabolic reprograming with enhanced glycolysis, Krebs cycle, and glutamine utilization. In addition, particulate β-glucan converts immunosuppressive TAM via the C-type lectin receptor dectin-1-induced spleen tyrosine kinase-Card9-Erk pathway. Further in vivo studies show that oral particulate β-glucan treatment significantly delays tumor growth, which is associated with in vivo TAM phenotype conversion and enhanced effector T cell activation. Mice injected with particulate β-glucan-treated TAM mixed with tumor cells have significantly reduced tumor burden with less blood vascular vessels compared with those with TAM plus tumor cell injection. In addition, macrophage depletion significantly reduced the therapeutic efficacy of particulate β-glucan in tumor-bearing mice. These findings have established a new paradigm for macrophage polarization and immunosuppressive TAM conversion and shed light on the action mode of β-glucan treatment in cancer. PMID: 26453753 [PubMed - as supplied by publisher]

Omics-Based Biomarkers: Application Of Metabolomics In Neuropsychiatric Disorders. Int J Neuropsychopharmacol. 2015 Oct 9; Authors: Sethi S, Brietzke E Abstract One of the major concerns of modern society is to identify putative biomarkers that serve as a valuable early diagnostic tool to identify a subset of patients with increased risk to develop neuropsychiatric disorders. Biomarker identification in neuropsychiatric disorders is proposed to offer a number of important benefits to patient well-being including prediction of forthcoming disease, diagnostic precision and a level of disease description that would guide treatment choice. Nowadays, metabolomics approach has unlocked new possibilities in diagnostics of devastating disorders like neuropsychiatric disorders. Metabolomics-based technologies has the potential to map early biochemical changes in disease and hence provides an opportunity to develop predictive biomarkers that can be used as indicators of pathological abnormalities prior to development of clinical symptoms of neuropsychiatric disorders. This review highlights different '-omics' strategies for biomarker discovery in neuropsychiatric disorders. We also highlight initial outcomes from metabolomics studies in psychiatric disorders such as schizophrenia, bipolar disorder and addictive disorders. This review will also present issues and challenges regarding the implementation of metabolomics approach as a routine diagnostic tool in the clinical laboratory in context with neuropsychiatric disorders. PMID: 26453695 [PubMed - as supplied by publisher]

Study of exhaled breath condensate sample preparation for metabolomics analysis by LC-MS/MS in high resolution mode. Talanta. 2015 Nov 1;144:1360-9 Authors: Fernández-Peralbo MA, Calderón Santiago M, Priego-Capote F, Luque de Castro MD Abstract Metabolomic analysis of exhaled breath condensate (EBC) requires an unavoidable sample preparation step because of the low concentration of its components, and potential cleanup for possible interferents. Sample preparation based on protein precipitation (PP), solid-phase extraction (SPE) by hydrophilic and lipophilic sorbents or lyophilization has demonstrated that the analytical sample from the last is largely the best because lyophilization allows reconstitution in a volume as small as required (preconcentration factors up to 80-times with respect to the original sample), thus doubling the number of detected compounds as compared with the other alternatives (47 versus 25). In addition, PP and/or SPE cleanup are unnecessary as no effect from the EBC components removed by these steps appears in the chromatograms. The total 49 EBC compounds tentatively identified and confirmed by MS/MS in this research include amino acids, fatty acids, fatty amides, fatty aldehydes, sphingoid bases, oxoanionic compounds, imidazoles, hydroxy acids and aliphatic acyclic acids. PMID: 26452970 [PubMed - in process]

Physiological and metabolomic analysis of Punica granatum (L.) under drought stress. Planta. 2015 Oct 9; Authors: Catola S, Marino G, Emiliani G, Huseynova T, Musayev M, Akparov Z, Maserti BE Abstract MAIN CONCLUSION: Punica granatum has a noticeable adaptation to drought stress. The levels of the green leaf volatile trans-2-hexenal increased in response to drought stress suggesting a possible role of this compound in drought stress response in pomegranate. Punica granatum (L.) is a highly valued fruit crop for its health-promoting effects and it is mainly cultivated in semi-arid areas. Thus, understanding the response mechanisms to drought stress is of great importance. In the present research, a metabolomics analysis was performed to evaluate the effects of drought stress on volatile organic compounds extracted from the leaves of pomegranate plants grown under water shortage conditions. The time course experiment (7 days of water deprivation and 24-h recovery) consisted of three treatments (control, drought stress, and rehydration of drought-stressed plants). Plant weights were recorded and control plants were irrigated daily at pot capacity to provide the lost water. Fraction of transpirable soil water has been evaluated as indicator of soil water availability in stressed plants. The levels of proline, hydrogen peroxide and lipid peroxidation as well as of the photosynthetic parameters such as photosynthesis rate (A), stomatal conductance (g s), photosynthetic efficiency of photosystem II, and photochemical quenching were monitored after the imposition of drought stress and recovery as markers of plant stress. Constitutive carbon volatile components were analyzed in the leaf of control and drought-stressed leaves using Head Space Solid Phase Micro Extraction sampling coupled with Gas Chromatography Mass Spectrometry. A total of 12 volatile compounds were found in pomegranate leaf profiles, mainly aldehydes, alcohols, and organic acids. Among them, the trans-2-hexenal showed a significant increase in water-stressed and recovered leaves respect to the well-watered ones. These data evidence a possible role of the oxylipin pathway in the response to water stress in pomegranate plants. PMID: 26452697 [PubMed - as supplied by publisher]

Related Articles Lowered circulating aspartate is a metabolic feature of human breast cancer. Oncotarget. 2015 Oct 1; Authors: Xie G, Zhou B, Zhao A, Qiu Y, Zhao X, Garmire L, Shvetsov YB, Yu H, Yen Y, Jia W Abstract Distinct metabolic transformation is essential for cancer cells to sustain a high rate of proliferation and resist cell death signals. Such a metabolic transformation results in unique cellular metabolic phenotypes that are often reflected by distinct metabolite signatures in tumor tissues as well as circulating blood. Using a metabolomics platform, we find that breast cancer is associated with significantly (p = 6.27E-13) lowered plasma aspartate levels in a training group comprising 35 breast cancer patients and 35 controls. The result was validated with 103 plasma samples and 183 serum samples of two groups of primary breast cancer patients. Such a lowered aspartate level is specific to breast cancer as it has shown 0% sensitivity in serum from gastric (n = 114) and colorectal (n = 101) cancer patients. There was a significantly higher level of aspartate in breast cancer tissues (n = 20) than in adjacent non-tumor tissues, and in MCF-7 breast cancer cell line than in MCF-10A cell lines, suggesting that the depleted level of aspartate in blood of breast cancer patients is due to increased tumor aspartate utilization. Together, these findings suggest that lowed circulating aspartate is a key metabolic feature of human breast cancer. PMID: 26452258 [PubMed - as supplied by publisher]

Related Articles Symptomatic migration of a Kirschner wire into the spinal canal without spinal cord injury: case report. J Neurosurg Spine. 2015 Oct 9;:1-4 Authors: Minić L, Lepić M, Novaković N, Mandić-Rajčević S Abstract The migration of Kirschner wires (K-wires) is a rare but significant complication of osteosynthesis interventions, and numerous cases of wire migrations have been reported in the literature. Nevertheless, migration into the spinal canal is very rare, with only 10 cases reported thus far. The authors present a case of K-wire migration into the spinal canal, together with a review of the relevant literature. A 30-year-old male who had suffered a right clavicle fracture in a motorcycle accident was treated with 2 K-wires. Four months after the initial fixation, while he was lifting his child, he experienced short-term pain in his back, numbness in all 4 extremities, followed by a spontaneous decrease in numbness affecting only the ulnar nerve dermatomes bilaterally, and a persistent headache. No urinary incontinence was present. Simple radiography studies of the cervical spine revealed a wire in the spinal canal, penetrating the T-2 foramen and reaching the contralateral foramen of the same vertebra. Computerized tomography showed the wire positioned in front of the spinal cord. Surgery for wire extraction was performed with the patient under general anesthesia, and he experienced relief of the symptoms immediately after surgery. This case is unique because the wire caused no damage to the spinal cord but did cause compression-related symptomatology and headache, which have not been reported in osteosynthesis wire migration to the thoracic region. PMID: 26451668 [PubMed - as supplied by publisher]

Related Articles An integrated metabolomics workflow for the quantification of sulfur pathway intermediates employing thiol protection with N-ethyl maleimide and hydrophilic interaction liquid chromatography tandem mass spectrometry. Analyst. 2015 Oct 9; Authors: Ortmayr K, Schwaiger M, Hann S, Koellensperger G Abstract The sulfur metabolic pathway is involved in basic modes of cellular metabolism, including methylation, cell division, respiratory oscillations and stress responses. Hence, the implicated high reactivity of the sulfur pathway intermediates entails challenges for their quantitative analysis. In particular the unwanted oxidation of the thiol group-containing metabolites glutathione, cysteine, homocysteine, γ-glutamyl cysteine and cysteinyl glycine must be prevented in order to obtain accurate snapshots of this important part of cellular metabolism. Suitable analytical methodologies are therefore needed to support studies of drug metabolism and metabolic engineering. In this work, a novel sample preparation strategy targeting thiolic metabolites was established by implementing thiol group protection with N-ethyl maleimide using a cold methanol metabolite extraction procedure. It was shown that N-ethyl maleimide derivatization is compatible with typical metabolite extraction procedures and also allowed for the stabilization of the instable thiolic metabolites in a fully (13)C-labeled yeast cell extract. The stable isotope labeled metabolite analogs could be used for internal standardization to achieve metabolite quantification with high precision. Furthermore, a dedicated hydrophilic interaction liquid chromatography tandem mass spectrometry method for the separation of sulfur metabolic pathway intermediates using a sub-2 μm particle size stationary phase was developed. Coupled with tandem mass spectrometry, the presented methodology proved to be robust, and sensitive (absolute detection limits in the low femtomole range), and allowed for the quantification of cysteine, cysteinyl glycine, cystathionine, cystine, glutamic acid, glutamyl cysteine, reduced glutathione, glutathione disulfide, homocysteine, methionine, S-adenosyl homocysteine and serine in a human ovarian carcinoma cell model. PMID: 26451393 [PubMed - as supplied by publisher]

Related Articles Trial Watch: Adoptive cell transfer for oncological indications. Oncoimmunology. 2015 Nov;4(11):e1046673 Authors: Aranda F, Buqué A, Bloy N, Castoldi F, Eggermont A, Cremer I, Fridman WH, Fucikova J, Galon J, Spisek R, Tartour E, Zitvogel L, Kroemer G, Galluzzi L Abstract One particular paradigm of anticancer immunotherapy relies on the administration of (potentially) tumor-reactive immune effector cells. Generally, these cells are obtained from autologous peripheral blood lymphocytes (PBLs) ex vivo (in the context of appropriate expansion, activation and targeting protocols), and re-infused into lymphodepleted patients along with immunostimulatory agents. In spite of the consistent progress achieved throughout the past two decades in this field, no adoptive cell transfer (ACT)-based immunotherapeutic regimen is currently approved by regulatory agencies for use in cancer patients. Nonetheless, the interest of oncologists in ACT-based immunotherapy continues to increase. Accumulating clinical evidence indicates indeed that specific paradigms of ACT, such as the infusion of chimeric antigen receptor (CAR)-expressing autologous T cells, are associated with elevated rates of durable responses in patients affected by various neoplasms. In line with this notion, clinical trials investigating the safety and therapeutic activity of ACT in cancer patients are being initiated at an ever increasing pace. Here, we review recent preclinical and clinical advances in the development of ACT-based immunotherapy for oncological indications. PMID: 26451319 [PubMed - as supplied by publisher]

Related Articles Natural killer cell mediated immunosurveillance of pediatric neuroblastoma. Oncoimmunology. 2015 Nov;4(11):e1042202 Authors: Semeraro M, Rusakiewicz S, Zitvogel L, Kroemer G Abstract Until recently, the pathophysiological impact of natural killer (NK) lymphocytes has been largely elusive. Capitalizing on our previous discovery that NK cells mediate immunosurveillance against gastrointestinal stromal tumors (GISTs), we have now investigated the potential influence of immunostimulatory and immunosuppressive isoforms of the NK receptor NKp30 on the fate of infants with neuroblastoma. In three independent cohorts of high-risk neuroblastoma, we observed a similar prognostic impact of the ratio of immunostimulatory vs. immunosuppressive NKp30 isoforms. Patients with high-risk neuroblastoma that are in remission after induction chemotherapy have a higher risk of relapse if their circulating and bone marrow NK cells express the preponderantly immunosuppressive NKp30 C isoform, as determined by a robust RT-PCR-based assay. We also found that neuroblastoma cells express the NKp30 ligand B7-H6, which can be shed from the tumor cells. Elevated soluble B7-H6 levels contained in patient sera inhibited NK functions in vitro and correlated with downregulation of NK-p30 on NK cells, as well as with bone marrow metastasis and chemoresistance. Altogether, these results support the contention that NK cells play a decisive role in the immunosurveillance of neuroblastoma. In light of these results, efforts should be undertaken to investigate NK cell functions in all major cancer types, with the obvious expectation of identifying additional NK cell-related prognostic or predictive biomarkers and improving NK cell based immunotherapeutic strategies against cancer. PMID: 26451315 [PubMed - as supplied by publisher]

Related Articles Does inorganic nitrate say NO to obesity by browning white adipose tissue? Adipocyte. 2015 Oct-Dec;4(4):311-4 Authors: Roberts LD Abstract The dietary constituent inorganic nitrate, found in large concentrations in green leafy vegetables, has beneficial effects on cardiometabolic health. Contemporary studies employing nitrate have demonstrated that the anion has anti-obesity and anti-diabetic properties; however the nitrate-mediated mechanisms for improving metabolic health remain unclear. Recently, we employed a combined histological, metabolomics, and transcriptional and protein analysis approach to establish that nitrate promoted the "browning" of white adipose tissue via the xanthine oxidoreductase catalyzed reductive nitrate-nitrite-nitric oxide pathway. Interestingly, it was observed that nitrate-stimulated brown adipose-associated gene expression in white adipose tissue was augmented in hypoxia. These findings not only suggest that protection from metabolic disease offered by vegetable consumption may, in part, be mediated through the effects of nitrate on white adipose tissue, but also, since hypoxia is a serious co-morbidity affecting adipose tissue in obese individuals, that nitrate may be effective in promoting the browning of adipose tissue to improve metabolic fitness. PMID: 26451288 [PubMed]