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Background: Several theories have been proposed to conceptualize the pathological processes inherent to schizophrenia. The 'prostaglandin deficiency' hypothesis postulates that defective enzyme systems converting essential fatty acids to prostaglandins lead to diminished levels of prostaglandins, which in turn affect synaptic transmission.Methods: Here we sought to determine the lipidomic profiles associated with schizophrenia in twin pairs discordant for schizophrenia as well as unaffected twin pairs. The study included serum samples from 19 twin pairs discordant for schizophrenia (mean age 51 ± 10 years; 7 monozygotic pairs; 13 female pairs) and 34 age and gender matched healthy twins as controls. Neurocognitive assessment data and gray matter density measurements taken from high-resolution magnetic resonance images were also obtained. A lipidomics platform using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry was applied for the analysis of serum samples.Results: In comparison to their healthy co-twins, the patients had elevated triglycerides and were more insulin resistant. They had diminished lysophosphatidylcholine levels, which associated with decreased cognitive speed.Conclusions: Our findings may be of pathophysiological relevance since lysophosphatidylcholines, byproducts of phospholipase A2-catalyzed phospholipid hydrolysis, are preferred carriers of polyunsaturated fatty acids across the blood-brain barrier. Furthermore, diminishment of lysophosphatidylcholines suggests that subjects at risk of schizophrenia may be more susceptible to infections. Their association with cognitive speed supports the view that altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins. © 2012 Orešič et al.; licensee BioMed Central Ltd.

Objective: Islet autoimmunity precedes type 1 diabetes and often initiates in childhood. Phenotypic variation in islet autoimmunity relative to the age of its development suggests heterogeneous mechanisms of autoimmune activation. To support this notion, we examined whether serum metabolite profiles differ between children with respect to islet autoantibody status and the age of islet autoantibody development.Research Design and Methods: The study analyzed 29 metabolites of amino acid metabolism and 511 lipids assigned to 12 lipid clusters in children, with a type 1 diabetic parent, who first developed autoantibodies at age 2 years or younger (n = 13), at age 8 years or older (n = 22), or remained autoantibody-negative, and were matched for age, date of birth, and HLA genotypes (n = 35). Ultraperformance liquid chromatography and mass spectroscopy were used to measure metabolites and lipids quantitatively in the first autoantibody-positive and matched autoantibody-negative serum samples and in a second sample after 1 year of follow-up.Results: Differences in the metabolite profiles were observed relative to age and islet autoantibody status. Independent of age-related differences, autoantibody-positive children had higher levels of odd-chain triglycerides and polyunsaturated fatty acid-containing phospholipids than autoantibody-negative children and independent of age at first autoantibody appearance (P < 0.0001). Consistent with our hypothesis, children who developed autoantibodies by age 2 years had twofold lower concentration of methionine compared with those who developed autoantibodies in late childhood or remained autoantibody-negative (P < 0.0001).Conclusions: Distinct metabolic profiles are associated with age and islet autoimmunity. Pathways that use methionine are potentially relevant for developing islet autoantibodies in early infancy. [ABSTRACT FROM AUTHOR]

Ceramides and IL-6 have a role in immune–inflammatory responses and cardiovascular diseases, and are suggested to be involved in insulin and glucose metabolism. We sought to assess the associations of circulating levels of IL-6, TNF-α and high-sensitivity C reactive protein (hsCRP), which are inflammatory markers related to insulin resistance (IR), with the plasma lipid metabolites ceramides and diacylglycerols (DAG) in patients with CHD. Cross-sectional analyses were carried out on data from 33 patients with CHD. Serum levels of the inflammatory markers and plasma lipid metabolites (lipidomics approach performed by ultra-performance liquid chromatography coupled to electrospray ionisation MS) were measured at the same time point as insulin resistance (IR) (HOMA-IR index). Serum circulating levels of IL-6 were strongly correlated with plasma ceramide concentrations ( r = 0.59, p < 0.001). Adjustments for serum TNF-α or hsCRP levels, smoking, BMI, age, sex or HOMA-IR did not change the results ( p < 0.001). After adjustments for the effect of serum inflammatory markers (TNF-α or hsCRP), HOMA-IR and BMI the correlation between plasma DAG and serum IL-6 ( r = 0.33) was also significant ( p < 0.03). In a linear regression model, circulating levels of both ceramides and TNF-α had a significant independent influence on circulating levels of IL-6, altogether accounting for 41% of its variation ( p < 0.001). Our results strongly suggest that the link between ceramides, IR and inflammation is related to the inflammatory marker IL-6. Ceramides may contribute to the induction of inflammation involved in IR states that frequently coexist with CHD. ClinicalTrials.gov NCT00720655 The study was supported by the Finnish Cultural Foundation, the North-Savo Regional Fund of the Finnish Cultural Foundation, the Yrjö Jahnsson Foundation, the Sigrid Juselius Foundation, the Juho Vainio Foundation, the Kuopio University Hospital (grant 510RA07), the Academy of Finland (Projects 117844 and 118590) and by the Nordic Centre of Excellence on ‘Systems biology in controlled dietary interventions and cohort studies’ (SYSDIET), Project 070014. [ABSTRACT FROM AUTHOR]

The global coffee production is facing serious challenges including land use, climate change, and sustainability while demand is rising. Cellular agriculture is a promising alternative to produce plant-based commodities such as coffee, which are conventionally produced by farming. In this study, the complex process of drying and roasting was adapted for bioreactor-grown coffee cells to generate a coffee-like aroma and flavor. The brews resulting from different roasting regimes were characterized with chemical and sensory evaluation-based approaches and compared to conventional coffee. Roasting clearly influenced the aroma profile. In contrast to conventional coffee, the dominant odor and flavor attributes were burned sugar-like and smoky but less roasted. The intensities of bitterness and sourness were similar to those of conventional coffee. The present results demonstrate a proof of concept for a cellular agriculture approach as an alternative coffee production platform and guide future optimization work.

Raspberry ketone has generated interest in recent years both as a flavor agent and as a health promoting supplement. Raspberry ketone can be synthesized chemically, but the value of a natural nonsynthetic product is among the most valuable flavor compounds on the market. Coumaroyl-coenzyme A (CoA) is the direct precursor for raspberry ketone but also an essential precursor for flavonoid and lignin biosynthesis in plants and therefore highly regulated. The synthetic fusion of 4-coumaric acid ligase (4CL) and benzalacetone synthase (BAS) enables the channeling of coumaroyl-CoA from the ligase to the synthase, proving to be a powerful tool in the production of raspberry ketone in both N. benthamiana and S. cerevisiae . To the best of our knowledge, the key pathway genes for raspberry ketone formation are transiently expressed in N. benthamiana for the first time in this study, producing over 30 μg/g of the compound. Our raspberry ketone producing yeast strains yielded up to 60 mg/L, which is the highest ever reported in yeast.

Angiogenesis is a complex physiological process that cannot be treated with single agent therapy. Several edible fungi have been known to encompass bioactive compounds, and are promising sources of multi-component drugs. One such widely consumed edible fungi is Cantharellus cibarius , which has been explored for its biological activities. The present study focused on assessing the anti-angiogenic activity of petroleum ether and ethanol extracts of C. cibarius using chick chorioallantoic membrane (CAM) assay. Both the extracts showed a dose-dependent response which was compared with the anti-angiogenic activity of the positive controls silibinin, and lenalidomide. The extracts were also studied for their lipoxygenase (LOX) inhibitory potential and compared to ascorbic acid as the positive control. The IC 50 values of the petroleum ether extract, ethanol extract, and ascorbic acid for LOX inhibition assay were 135.4, 113.1, and 41.5 µg/mL, respectively. Although both the extracts showed similar responses in CAM assay, ethanol extract proved to be more potent in LOX inhibition assay. Finally, the extracts were investigated for their chemical composition using GC-MS. A correlation between LOX inhibition and anti-angiogenic potential was established at the molecular level. A meticulous literature search was carried out to correlate the biochemical composition of the extracts to their anti-angiogenic activity.

Dihydronaphthoquinones are described as constituents of sundews ( Drosera ), Venus flytraps ( Dionaea ), and dewy pines ( Drosophyllum ) for the first time. As in the corresponding naphthoquinones, these reduced derivatives may occur in two regio-isomeric series distinguished by the relative position of a methyl group (at position 2 or 7 in the naphthalene skeleton), depending on the taxon. Species producing plumbagin (2-methyljuglone, 1 ) do commonly contain the corresponding dihydroplumbagin ( 5 ), while species containing ramentaceone (7-methyljuglone, 2 ) also contain dihydroramentaceone (7-methyl-β-dihydrojuglone, 6 ). So far, only few species containing plumbagin ( 1 ) and dihydroplumbagin ( 5 ) additionally form dihydroramentaceone ( 6 ) but not ramentaceone ( 2 ). Thus, subtle but constant differences in the chemism of closely related and morphologically similar species reliably define and distinguish taxa within D . sect. Arachnopus , which is taken to exemplify their chemotaxonomic utility. The joint presence of quinones and hydroquinones allows observations and predictions on the chemical structures and the reactions of these intriguing natural products.

Fungi are a huge source of unexplored bioactive compounds. Owing to their biological activities, several fungi have shown commercial application in the health industry. Tuber aestivum Vittad. is one such edible fungi with an immense scope for practical biological applications. In the present study, the anti-angiogenic activity of petroleum ether and ethanol extracts of T. aestivum was investigated using the chick chorioallantoic membrane assay and compared to the positive controls silibinin and lenalidomide. Both the extracts showed a dose-dependent anti-angiogenic response. The extracts were also assessed for their anti-inflammatory potential by lipoxygenase-inhibition assay. The IC 50 values for LOX inhibition assay, computed by the Boltzmann plot, were 368.5, 147.3 and 40.2 µg/mL, for the petroleum ether extract, ethanol extract, and the positive control ascorbic acid, respectively. The ethanol extract of T. aestivum showed superior anti-angiogenic and anti-inflammatory activity than the petroleum ether extract. Compositional investigation of the extracts by GC-MS revealed the presence of various bioactive compounds. The compounds were correlated to their anti-angiogenic and anti-inflammatory activity based on a meticulous literature search., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Aqueous autolysate from the snake Eryx miliaris (SNA) has been used in traditional medicine of Uzbekistan as anti-inflammatory, hepatoprotective and immunomodulatory agent. However, little is known about the chemical composition and its mechanisms of activity., Aim of the Study: This is our first attempt to analyse the composition of snake autolysate using gas chromatography with mass spectrometry (GC-MS) and to investigate the mechanisms of anti-inflammatory and hyaluronidase activity of fingerprinted E. miliaris autolysate to support their use in the traditional Uzbek medicine., Materials and Methods: Aqueous autolysate was evaporated and derivatised for GC-MS analysis of metabolites. For quantification, lipids were extracted from autolysate by solvent extraction and derivatised by esterification and silylation. Biological activity was evaluated with lipid peroxidation, cyclooxygenase (COX) inhibition and antihyaluronidase activity tests., Results: GC-MS analysis of SNA enabled the identification of 27 compounds. Short chain fatty acids (SCFA, 21%), amino acid/derivatives 39% (incl. 2-piperidinone 19%), phenyl (7%), and OH-Phenyl (10%) derivatives covered 77%. Other derivatives (9%) included succinic acid and 3-indole acetic acid). Long chain fatty acids (C 16 -C 18 ) accounted for 3%. The lipid concentration of SNA was 1.2 mg/mL (0.12%). Three concentration levels (1.0-20.0 μg/mL) did not inhibit COX-1 and COX-2 in vitro and malondialdehyde level was not decreased by SNA in lipid peroxidation model. However, SNA was a potent inhibitor of the hyaluronidase enzyme activity in a dose dependent manner with IC 50  = 0.086 mL/mL., Conclusion: The results from GC-MS analyses of SNA lead us to the identification of a wide range of major chemical structures of the metabolites and their derivatives with several categories. Pharmacological studies support the traditional use of SNA and show one of its possible mechanisms of activity via inhibition of hyaluronidase., (Copyright © 2019 Elsevier B.V. All rights reserved.)