Hypoxanthine Levels Research Articles

Metabolomic interference induced by short-chain chlorinated paraffins in human normal hepatic cells

Short-chain chlorinated paraffins (SCCPs) are an emerging class of persistent organic pollutants (POPs) that are widely detected in environmental matrices and human samples. Because of their environmental persistence, long-range transport potential, bioaccumulation potential, and biotoxicity, SCCPs pose a significant threat to human health. In this study, metabolomics technology was applied to reveal the metabolomic interference in human normal hepatic (L02) cells after exposure to low (1 μg/L), moderate (10 μg/L), and high (100 μg/L) doses of SCCPs. Principal component analysis (PCA) and metabolic effect level index (MELI) values showed that all three SCCP doses caused notable metabolic perturbations in L02 cells. A total of 72 metabolites that were annotated by MS/MS and matched with the experimental spectra in the Human Metabolome Database (HMDB) or validated by commercially available standards were selected as differential metabolites (DMs) across all groups. The low-dose exposure group shared 33 and 36 DMs with the moderate- and high-dose exposure groups, respectively. The moderate-dose exposure group shared 46 DMs with the high-dose exposure group. In addition, 33 DMs were shared among the three exposure groups. Among the 72 DMs, 9, 9, and 45 metabolites participated in the amino acid, nucleotide, and lipid metabolism pathways, respectively. The results of pathway enrichment analysis showed that the most relevant metabolic pathways affected by SCCPs were the lipid metabolism, fatty acid β-oxidation, and nucleotide metabolism pathways, and that compared with low-dose exposure, moderate- and high-dose SCCP exposures caused more notable perturbations of these metabolic pathways in L02 cells. Exposure to SCCPs perturbed glycerophospholipid and sphingolipid metabolism. Significant alterations in the levels of phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins indicated SCCP-induced biomembrane damage. SCCPs inhibited fatty acid β-oxidation by decreasing the levels of short- and medium-chain acylcarnitines in L02 cells, indicating that the energy supplied by fatty acid oxidation was reduced in these cells. Furthermore, compared with low- and moderate-dose SCCPs, high-dose SCCPs produced a significantly stronger inhibition of fatty acid β-oxidation. In addition, SCCPs perturbed nucleotide metabolism. The higher hypoxanthine levels observed in L02 cells after SCCP exposures indicate that SCCPs may induce several adverse effects, including hypoxia, reactive oxygen species production, and mutagenesis in L02 cells.

Metabolomics analysis of serum and urine in type 1 diabetes patients with different time in range derived from continuous glucose monitoring

BackgroundTime in range (TIR), as an important glycemic variability (GV) index, is clearly associated with disease complications in type 1 diabetes (T1D). Metabolic dysregulation is also involved in the risks of T1D complications. However, the relationship between metabolites and TIR remains poorly understood. We used metabolomics to investigate metabolic profile changes in T1D patients with different TIR.MethodsThis study included 85 T1D patients and 81 healthy controls. GV indices, including TIR, were collected from continuous glucose monitoring system. The patients were compared within two subgroups: TIR-L (TIR < 50%, n = 21) and TIR-H (TIR > 70%, n = 14). To screen for differentially abundant metabolites and metabolic pathways, serum and urine samples were obtained for untargeted metabolomics by ultra-performance liquid chromatography‒mass spectrometry. Correlation analysis was conducted with GV metrics and screened biomarkers.ResultsMetabolites were significantly altered in T1D and subgroups. Compared with healthy controls, T1D patients had higher serum levels of 5-hydroxy-L-tryptophan, 5-methoxyindoleacetate, 4-(2-aminophenyl)-2,4-dioxobutanoate, and 4-pyridoxic acid and higher urine levels of thromboxane B3 but lower urine levels of hypoxanthine. Compared with TIR-H group, The TIR-L subgroup had lower serum levels of 5-hydroxy-L-tryptophan and mevalonolactone and lower urine levels of thromboxane B3 and phenylbutyrylglutamine. Dysregulation of pathways, such as tryptophan, vitamin B6 and purine metabolism, may be involved in the mechanism of diabetic complications related to glycemic homeostasis. Mevalonolactone, hypoxanthine and phenylbutyrylglutamine showed close correlation with TIR.ConclusionsWe identified altered metabolic profiles in T1D individuals with different TIR. These findings provide new insights and merit further exploration of the underlying molecular pathways relating to diabetic complications.

Identification of a novel biomarker for sarcopenia diagnosis using serum metabolomic analysis: a pilot study.

This pilot study compared serum metabolites in participants with and without sarcopenia. Metabolomic techniques were applied to identify serum metabolites and novel biomarkers specific to patients with sarcopenia. In accordance with AWGS2019 criteria, sarcopenia was defined as low muscle mass plus either low muscle strength/low physical function, and severe sarcopenia was defined as low muscle mass, low muscle strength, and low physical function all together. The sarcopenia group had higher hypoxanthine, galactose, and mannose levels but lower triethanolamine and homogentisic acid levels than the non-sarcopenia group. The severe sarcopenia group had lower levels of alpha-tocopherol than the mild and moderate sarcopenia groups. This study is the first to identify hypoxanthine as a potential biomarker for sarcopenia in humans and provides new insights into the pathophysiology of sarcopenia. Furthermore, the identified metabolites may be useful for the early detection of sarcopenia.

Peningkatan Kualitas Emping Melinjo melalui Proses Pengepresan dan Penurunan Kadar Purin di UKM Emping Jago

&lt;em&gt;&lt;em&gt;&lt;strong&gt;Quality Improvement of Emping Melinjo through Pressing Process and Reduction of Purin Level at SME Emping Jago.&lt;/strong&gt; &lt;/em&gt;Emping melinjo is one of the popular foods among Indonesians. Kartasura is one of the districts in Sukoharjo that has potential in the production of emping melinjo. This study aimed to improve the quality of emping melinjo by using a mechanical pressing machine and reducing the purin level. The method used was a literature review based on scientific journals, books, and others. The results were to substitute the pressing process using mechanical machinery and by soaking treatment to reduce the purin levels. The improvement on pressing process were performed as an innovation so the process will not depend on human workers. Then, the soaking in a 4% acetic acid solution (vinegar) varied for 0; 10; 20; and 40 minutes.The hypoxanthine and adenine levels (in micrograms per gram), according to the soaking duration, showed 46,43; 41,50; 41,05; 36,71; and 124,74; 110,90; 109,83; 108,82 respectively. &lt;em&gt;The 40 minutes soaking process could decrease the purin level by 20%.&lt;/em&gt;&lt;/em&gt;

Yohimbine Ingestion Mitigates Morning-Associated Decrements in High-Intensity Exercise Performance

Exercise performance tends to suffer during the morning compared to the evening, which may decrease potential training adaptations. Currently, it is unclear how nutritional interventions may affect this phenomenon and whether supplementation may allow for the attainment of optimal performance regardless of the time of day. The purpose of this study was to investigate the effects of acute yohimbine ingestion on morning-associated decrements in performance and psychophysiological responses to exercise. Physically active females (n = 16) were recruited to participate in three total visits, each with a different treatment: (1) placebo-morning (PL-AM), (2) yohimbine-morning (YHM-AM; oral 2.5 mg), and (3) placebo-afternoon (PM). The morning and afternoon visits occurred between 7:00–8:00 h and 16:00–17:00 h, respectively. The experimental treatments in the morning were ingested 20 min prior to capillary blood collection, which was completed pre- and post-exercise. Following a warm-up, participants completed a 2000 m time trial on a rowing ergometer. Power output, heart rate (HR), and rating of perceived exertion (RPE) were recorded every minute. Time to competition (TTC) and subjective energy, focus, and alertness were documented post-exercise. Pre- and post-exercise blood lactate (La) and plasma hypoxanthine (HX) levels were also assessed. The trials were separated by a 48 h washout period. The results showed that power output (p = 0.010) was lower and TTC (p = 0.003) was significantly slower with PL-AM compared to PM. Furthermore, YHM-AM resulted in higher power output (p = 0.035) and faster TTC (p = 0.007) compared to PL-AM, with no differences compared to PM (p &gt; 0.05). Post-exercise La was significantly lower with YHM-AM compared to PL-AM (p = 0.046) and PM (p = 0.001). Pre-exercise plasma HX, as measured via conversion to xanthine, was significantly higher with PM (p = 0.039), while the levels trended higher with YHM-AM (p = 0.060) compared to PL-AM. Subjective energy was higher with YHM-AM (p = 0.045) and PM (p = 0.009) compared to PL-AM, while alertness was only higher for YHM-AM compared to PL-AM (p = 0.045). No statistical differences between the treatments were found for RPE or HR (p &gt; 0.05). These findings indicate that YHM ingestion attenuates performance decrements in the morning. Improvements in performance may be underpinned by improved feelings of energy and alterations in metabolism. Practically, YHM may represent an effective ergogenic aid to combat a lack of energy and low performance during the morning.

The toxicity response of the electrochemical signal of the cell to the drug metabolized by the S9 system.

The electrochemical detection method of cytotoxicity using intracellular purines as biomarkers has shown great potential for in vitro drug toxicity evaluation. However, no electrochemical detection system based on an in vitro drug metabolism mechanism has been devised. In this paper, electrochemical voltammetry was used to investigate the effect of the S9 system on the electrochemical behavior of HepG2 cells, and benzo[a]pyrene, fluoranthene, and pyrene were employed to investigate the sensitivity of electrochemical signals of cells to the cytotoxicity of drugs metabolized by the S9 system. The results showed that, within 8 h of exposure to the S9 system, the electrochemical signal of HepG2 cells at 0.7 V did not alter noticeably. The levels of xanthine, guanine, hypoxanthine, and adenine in the cells were not significantly altered. Compared with the absence of S9 system metabolism, benzo[a]pyrene and fluoranthene processed by the S9 system decreased the electrochemical signal of the cells in a dose-dependent manner, while pyrene did not change it appreciably. HPLC also revealed that benzo[a]pyrene and fluoranthene metabolized by the S9 system decreased the intracellular purine levels, whereas pyrene had no effect on them before and after S9 system metabolism. The cytotoxicity results of the three drugs examined by electrochemical voltammetry and MTT assay showed a strong correlation and good agreement. The S9 system had no effect on the intracellular purine levels or the electrochemical signal of cells. When the drug was metabolized by the S9 system, variations in cytotoxicity could be precisely detected by electrochemical voltammetry.

Electrochemistry detection of estrogenic effect: Regulation of de novo purine synthesis and catabolism by gibberellin and fulvestrant

The estrogenic effect of plant growth regulators has been received little attention, which leads to the lack of relevant toxicity data. In this study, the estrogenic effect induced by gibberellin with ERα-dependent manner was found by E-screen and western blot methods, and the electrochemical signals of MCF-7 cells regulated by gibberellin and fulvestrant were investigated. The results showed that the electrochemical signals of MCF-7 cells were increased by gibberellin, while reduced by fulvestrant significantly, and displayed an extremely sensitive response to the effects of estrogenic effect induced by ERα agonist and antagonist. Western blot results showed that the expressions of phosphoribosyl pyrophosphate amidotransferase and hypoxanthine nucleotide dehydrogenase in de novo purine synthesis and adenine deaminase in catabolism were more effective regulated by gibberellin and fulvestrant, resulting in significant changes of the levels of guanine, hypoxanthine and xanthine in cells, and then electrochemical signals. The results provide a theoretical basis for the establishment of new electrochemical detection method of the estrogenic effect of plant regulators.

Xanthine or hypoxanthine or both may play therapeutical effect in Parkinson's disease through the endocannabinoid system

Parkinson's disease (PD) is a common neurodegenerative disorder. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra striata and the extensive accumulation of α-synuclein in different brain regions. The substantia nigra and striatum are brain regions with high expression of cannabinoid receptors, and the role of the endogenous cannabinoid system (ECS) has been explored in PD. The ECS may be a promising target for the treatment of PD. The correlation between PD and serum uric acid levels has been demonstrated in a large number of studies, but a causal relationship between the two has not been proven. Xanthine and hypoxanthine are upstream metabolite of uric acid, and they have been shown to be effective in relieving PD symptoms. Therefore, we hypothesized that xanthine or hypoxanthine or both may increase the inhibitory properties of GABAergic neurons by increasing the sensitivity of cannabinoid receptors on GABAergic neurons in the striatum, thereby activating the direct nigrostriatal pathway to ameliorate Parkinson's disease symptoms. The proposed hypothesis can be tested in animal and cellular intervention experiments. If this approach is found to be effective in improving PD symptoms with minimal adverse events, exogenous supplementation of xanthine/ hypoxanthine or the use of xanthine oxidase to block its metabolism to elevate hypoxanthine levels could potentially be an effective addition to PD therapy.

Association Between Human Metabolomics and Rheumatoid Arthritis: A Systematic Review and Meta-analysis

The underdiagnosis and inadequate treatment of rheumatoid arthritis (RA) can be attributed to the various clinical manifestations presented by patients. To address this concern, we conducted an extensive review and meta-analysis, focusing on RA-related metabolites. A comprehensive literature search was conducted in PubMed, the Cochrane Library, Web of Science, and Embase to identify relevant studies published up to October 5, 2022. The quality of the included articles was evaluated and, subsequently, a meta-analysis was conducted using Review Manager software to analyze the association between metabolites and RA. Forty nine studies met the inclusion criteria for the systematic review, and six of these studies were meta-analyzed to evaluate the association between 28 reproducible metabolites and RA. The results indicated that, compared to controls, the levels of histidine (RoM=0.83, 95% CI=0.79-0.88, I2=0%), asparagine (RoM=0.83, 95% CI=0.75-0.91, I2=0%), methionine (RoM=0.82, 95% CI=0.69-0.98, I2=85%), and glycine (RoM=0.81, 95% CI=0.67-0.97, I2=68%) were significantly lower in RA patients, while hypoxanthine levels (RoM=1.14, 95% CI=1.09-1.19, I2=0%) were significantly higher. This study identified histidine, methionine, asparagine, hypoxanthine, and glycine as significantly correlated with RA, thus offering the potential for the advancement of biomarker discovery and the elucidation of disease mechanisms in RA.

Diurnal Variations in Serum Uric Acid, Xanthine, and Xanthine Oxidoreductase Activity in Male Patients with Coronary Artery Disease.

Hyperuricemia is influenced by diet and can cause gout. Whether it is a potential risk factor for cardiovascular disease (CVD) remains controversial, and the mechanism is unclear. Similar to CVDs, gout attacks occur more frequently in the morning and at night. A possible reason for this is the diurnal variation in uric acid (UA), However, scientific data regarding this variation in patients with CVD are not available. Thus, we aimed to investigate diurnal variations in serum levels of UA and plasma levels of xanthine, hypoxanthine, and xanthine oxidoreductase (XOR) activity, which were measured at 18:00, 6:00, and 12:00 in male patients with coronary artery disease. Thirty eligible patients participated in the study. UA and xanthine levels significantly increased from 18:00 to 6:00 but significantly decreased from 6:00 to 12:00. By contrast, XOR activity significantly increased both from 18:00 to 6:00 and 6:00 to 12:00. Furthermore, the rates of increase in UA and xanthine levels from night to morning were significantly and positively correlated. In conclusion, UA and xanthine showed similar diurnal variations, whereas XOR activity showed different diurnal variations. The morning UA surge could be due to UA production. The mechanism involved XOR activity, but other factors were also considered.

Corneal metabolic biomarkers for moderate and high myopia in human

This study aimed to identify the corneal metabolic biomarkers for moderate and high myopia in human. We enrolled 221 eyes from 221 subjects with myopia to perform the femtosecond laser small incision lenticule extraction (SMILE) surgery. Among these, 71 eyes of 71 subjects were enrolled in the low myopic group, 75 eyes of 75 subjects in the moderate myopic group and 75 eyes of 75 subjects in the high myopic group. The untargeted metabolomics analysis was performed to analyze the corneal tissues extracted during the SMILE surgery using an ultra-high-performance liquid chromatography (UHPLC) coupled to a quadrupole time-of-flight (Q-TOF) mass spectrometry (MS). The one-way analysis of variance (ANOVA) was used to identify the different metabolites among the three myopic groups, the orthogonal partial least-squares discriminant analysis (OPLS-DA) model was used to reveal the different metabolites between moderate myopia and low myopia, and between high myopia and low myopia. The Venn gram was used to find the overlapped metabolites of the three datasets of the different metabolites. The stepwise multiple linear regression analysis was used to determine the metabolic molecules associated with manifest refractive spherical equivalents (MRSE). The Receiver Operating Characteristics (ROC) analysis was performed to reveal the corneal biomarkers for moderate and high myopia. The hub biomarker was further selected by the networks among different metabolites created by the Cytoscape software. A total of 1594 metabolites were identified in myopic corneas. 321 metabolites were different among the three myopic groups, 106 metabolites were different between high myopic corneas and low myopic corneas, 104 metabolites were different between moderate myopic corneas and low myopic corneas, and 30 metabolic molecules overlapped among the three datasets. The multivariate linear regression analysis revealed the myopic degree was significantly influenced by the corneal levels of azelaic acid, arginine-proline (Arg-Pro), 1-stearoyl-2-myristoyl-sn-glycero-3-phosphocholine, and hypoxanthine. The ROC curve analysis showed that azelaic acid, Arg-Pro and hypoxanthine were effective in discriminating low myopia from moderate to high myopia with the area under the curve (AUC) values as 0.982, 0.991 and 0.982 for azelaic acid, Arg-Pro and hypoxanthine respectively. The network analysis suggested that Arg-Pro had the maximum connections among these three biomarkers. Thus, this study identified azelaic acid, Arg-Pro and hypoxanthine as corneal biomarkers to discriminate low myopia from moderate to high myopia, with Arg-Pro serving as the hub biomarker for moderate and high myopia.

5,7-Dimethoxycoumarin ameliorates vincristine induced neuropathic pain: potential role of 5HT3 receptors and monoamines.

Vincristine is the drug of choice for Hodgkin's lymphoma, acute lymphoblastic leukemia, and non-Hodgkin lymphoma. Despite its significant anticancer effects, it causes dose-dependent neuropathy, leading to compulsive dose reduction. The available drugs used for vincristine-induced neuropathic pain (VINP) have a range of safety, efficacy, and tolerability issues prompting a search for new therapies. 5,7-Dimethoxycoumarin (5,7-DMC) also known as citropten, is a natural coumarin found in the essential oils of citrus plants such as lime, lemons, and bergamots, and it possesses both antidepressant and anti-inflammatory effects. This study was designed to investigate the possible analgesic and antiallodynic effects of 5,7-DMC in a murine model of VINP. Vincristine was administered to groups of BALB/c male mice (0.1mg/kg intraperitoneally) once daily for 14days to induce VINP. Thermal hyperalgesia and mechanical allodynia were quantified using the tail immersion test and von Frey filament application method. The levels of monoamine neurotransmitters and vitamin C in frontal cortical, striatal and hippocampal tissues, as well as the TNF-α level in plasma, were quantified using high performance liquid chromatography and ELISA respectively. On day 15 of the protocol, acute treatment with 5,7-DMC clearly reversed VINP thermal hyperalgesia, mechanical static allodynia, mechanical dynamic allodynia, and cold allodynia. The activity of 5,7-DMC against hyperalgesia and allodynia was inhibited by pretreatment with ondansetron but not naloxone, implicating a 5-HT3 receptor involvement. VINP vitamin C levels were restored by 5,7-DMC in the frontal cortex, and changes in serotonin, dopamine, adenosine, inosine and hypoxanthine levels caused by vincristine were reversed either fully or partially. Additionally, the vincristine-induced rise in hippocampal serotonin, dopamine, inosine and striatal serotonin was appreciably reversed by 5,7-DMC. 5,7-DMC also reversed the vincristine-induced increase in the plasma level of TNF-α. In negating the changes in the levels of some neurotransmitters in the brain caused by vincristine, 5,7-DMC showed stronger effects than gabapentin. It was concluded that, there is a potential role of 5-HT3 receptors and monoamines in the amelioration of VINP induced by 5,7-DMC, and the use of this compound warrants further investigation.

Urinary Metabolic Distinction of Niemann-Pick Class 1 Disease through the Use of Subgroup Discovery.

In this investigation, we outline the applications of a data mining technique known as Subgroup Discovery (SD) to the analysis of a sample size-limited metabolomics-based dataset. The SD technique utilized a supervised learning strategy, which lies midway between classificational and descriptive criteria, in which given the descriptive property of a dataset (i.e., the response target variable of interest), the primary objective was to discover subgroups with behaviours that are distinguishable from those of the complete set (albeit with a differential statistical distribution). These approaches have, for the first time, been successfully employed for the analysis of aromatic metabolite patterns within an NMR-based urinary dataset collected from a small cohort of patients with the lysosomal storage disorder Niemann-Pick class 1 (NPC1) disease (n = 12) and utilized to distinguish these from a larger number of heterozygous (parental) control participants. These subgroup discovery strategies discovered two different NPC1 disease-specific metabolically sequential rules which permitted the reliable identification of NPC1 patients; the first of these involved 'normal' (intermediate) urinary concentrations of xanthurenate, 4-aminobenzoate, hippurate and quinaldate, and disease-downregulated levels of nicotinate and trigonelline, whereas the second comprised 'normal' 4-aminobenzoate, indoxyl sulphate, hippurate, 3-methylhistidine and quinaldate concentrations, and again downregulated nicotinate and trigonelline levels. Correspondingly, a series of five subgroup rules were generated for the heterozygous carrier control group, and 'biomarkers' featured in these included low histidine, 1-methylnicotinamide and 4-aminobenzoate concentrations, together with 'normal' levels of hippurate, hypoxanthine, quinolinate and hypoxanthine. These significant disease group-specific rules were consistent with imbalances in the combined tryptophan-nicotinamide, tryptophan, kynurenine and tyrosine metabolic pathways, along with dysregulations in those featuring histidine, 3-methylhistidine and 4-hydroxybenzoate. In principle, the novel subgroup discovery approach employed here should also be readily applicable to solving metabolomics-type problems of this nature which feature rare disease classification groupings with only limited patient participant and sample sizes available.

Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy

BackgroundThe pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP.MethodsWe recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls. 16S rRNA sequencing and nontargeting metabolomics were adapted to explore the gut microbiome and fecal metabolites.ResultsAn increase in richness and a dramatic deviation in composition were found in the gut microbiome in ICP. Decreased Firmicutes and Bacteroidetes abundances and increased Proteobacteria abundances were found in women with severe but not mild ICP compared to healthy pregnant women. Escherichia-Shigella and Lachnoclostridium abundances increased, whereas Ruminococcaceae abundance decreased in ICP group, especially in severe ICP group. The fecal metabolite composition and diversity presented typical variation in severe ICP. A significant increase in bile acid, formate and succinate levels and a decrease in butyrate and hypoxanthine levels were found in women with severe ICP. The MIMOSA model indicated that genera Ruminococcus gnavus group, Lachnospiraceae FCS020 group, and Lachnospiraceae NK4A136 group contributed significantly to the metabolism of hypoxanthine, which was significantly depleted in subjects with severe ICP. Genus Acinetobacter contributed significantly to formate metabolism, which was significantly enriched in subjects with severe ICP.ConclusionsWomen with severe but not mild ICP harbored a unique gut microbiome and fecal metabolites compared to healthy controls. Based on these profiles, we hypothesized that the gut microbiome was involved in bile acid metabolism through metabolites, affecting ICP pathogenesis and development, especially severe ICP.

L-arginine metabolism inhibits arthritis and inflammatory bone loss

ObjectivesTo investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss.MethodsL-arginine was applied to three arthritis models (collagen-induced arthritis, serum-induced arthritis and human TNF transgenic mice). Inflammation...

Comparative metabolic profiling of Cabernet Sauvignon wines reveals the potential of different Wickerhamomyces anomalus co-fermented with commercial Saccharomyces cerevisiae

In this paper, five Wickerhamomyces anomalus accumulated 9.1–19.7% less released CO2 than S. cerevisiae in the synthetic must. Untargeted metabolomics was used to analyze co-fermented real Cabernet Sauvignon wines. The results showed that all W. anomalus strains significantly decreased the levels of malic acid and hypoxanthine in co-fermented wines, thereby promoting the process of TCA cycle and purine metabolism, respectively. Furthermore, WG5, WG26, and WG27 strains utilized more amino acid, thus favoring the enhancement of aroma compounds. WG27 strain also could biotransform more odorless metabolites into flavor active compounds, such as phenethyl alcohol, indole and indole-3-acetaldehyde. Notably, WG27 strain significantly up-regulated secondary metabolites by more than 400% compared to the other W. anomalus strains. These secondary metabolites were involved in phenylpropanoid and flavonoid metabolism, tryptophan metabolism and methionine metabolism. In addition, co-fermentation with the WG27 strain also resulted in an increase in antioxidant activities by more than 16.09% compared to the control wine. This suggests that the WG27 strain not only improves the flavor and style of the wine but also enhances its antioxidant properties. The findings can be helpful in expanding general understanding of W. anomalus and its potential applications in the food and beverage industry.

Hypoxanthine Induces Signs of Bladder Aging With Voiding Dysfunction and Lower Urinary Tract Remodeling.

Lower urinary tract syndrome (LUTS) is a group of urinary tract symptoms and signs that can include urinary incontinence. Advancing age is a major risk factor for LUTS; however, the underlying biochemical mechanisms of age-related LUTS remain unknown. Hypoxanthine (HX) is a purine metabolite associated with generation of tissue-damaging reactive oxygen species (ROS). This study tested the hypothesis that exposure of the adult bladder to HX-ROS over time damages key LUT elements, mimicking qualitatively some of the changes observed with aging. Adult 3-month-old female Fischer 344 rats were treated with vehicle or HX (10 mg/kg/day; 3 weeks) administered in drinking water. Targeted purine metabolomics and molecular approaches were used to assess purine metabolites and biomarkers for oxidative stress and cellular damage. Biomechanical approaches assessed LUT structure and measurements of LUT function (using custom-metabolic cages and cystometry) were also employed. HX exposure increased biomarkers indicative of oxidative stress, pathophysiological ROS production, and depletion of cellular energy with declines in NAD+ levels. Moreover, HX treatment caused bladder remodeling and decreased the intercontraction interval and leak point pressure (surrogate measure to assess stress urinary incontinence). These studies provide evidence that in adult rats chronic exposure to HX causes changes in voiding behavior and in bladder structure resembling alterations observed with aging. These results suggest that increased levels of uro-damaging HX were associated with ROS/oxidative stress-associated cellular damage, which may be central to age-associated development of LUTS, opening up potential opportunities for geroscience-guided interventions.

Urate oxidase treatment increases the quality of autumn Yellowish Yinghong 9 black tea

Microbes can be used to improve the quality of fermented beverages and food. Colletotrichum camelliae is one of the most dominant fungi associated with tea leaves. In the present study, black tea produced from the autumn leaves of Yellowish Yinghong 9 was treated with C. camelliae urate oxidase (CcUOX) to determine whether this treatment could improve tea quality. The effects of recombinant CcUOX on several black tea quality parameters were assessed, such as liquor color, aroma, and levels of theabrownins, thearubigins, total polyphenols, catechins, caffeine, xanthine, and hypoxanthine. CcUOX treatment significantly affected the aroma composition and volatile compound profiles. Specifically, volatiles in the benzenoid/phenylpropanoid, fatty acid metabolism, and amino acid pathways were increased in CcUOX-treated black tea, whereas levels of volatiles in the terpineol and carotenoid pathways were reduced. This suggested that the balance of aroma constituents in Yellowish Yinghong 9 black tea was affected by treatment with CcUOX. The present study provides evidence that pre-treatment of black tea with a single enzyme from a common tea-associated microbe could significantly improve autumn tea quality, validating this method for use in further studies of tea improvement.

NMR metabolomics in bladder cancer: Identification and monitoring of serum biomarkers during Pt-based treatment.

3057 Background: To date, predictive and prognostic biomarkers for Bladder Cancer (BC) are lacking. Metabolomics, the study of small molecules involved in metabolism, aims to identify diagnostic, predictive and prognostic biomarkers. Overall, BC shows perturbations of various metabolic pathways, involved in biochemical reactions essential for energy production and for the maintenance of the REDOX balance, as well as in the metabolism of purines and pyrimidines. The main objective of this study is to characterize the serum metabolic profile of patients with BC undergoing platinum-based chemotherapy (Pt-CT), to identify the alterations induced by CT and evaluate the associated deregulated metabolic pathways, in order to identify potential biomarkers, prognostic and predictive of response to treatment. Methods: We enrolled patients with BC undergoing Pt-CT in different settings (neoadjuvant, adjuvant or metastatic). For each patient, a blood sample was collected before the start of each CT cycle (T0, T1, Tn). Metabolomic analysis was performed using the Bruker Avance 600 spectrometer. At baseline (T0), the metabolomic profiles of BC patients were compared with that of age- and sex-matched healthy controls. Major metabolites up- or down-regulated in patients with BC at baseline, were then monitored during CT (T1, Tn). Results: 14 patients were enrolled. When compared with age- and sex-matched healthy controls, patients with BC had elevated levels of acetate and acetone (ketone bodies), hypoxanthine, trimethylamine N-oxide (TMAO), glutamate, lactate, phenylalanine, and ornithine, and decreased levels of carnitine, choline, betaine, aspartate, threonine, 2-hydroxybutyrate, 2-aminobutyrate and histidine. When monitored during CT, hypoxanthine, glutamate, and aspartate levels increased; acetone, acetate and TMAO instead had a decreasing trend. Conclusions: The results of our pilot study confirm perturbations in several metabolic pathways: up-regulation of lactate, ketone bodies, hypoxanthine, phenylalanine, and glutamate levels in BC patients reflects altered glycolysis, fatty acid, purine, and amino acid metabolism, respectively. In addition, TMAO may play a role in the development of BC by promoting a pro-inflammatory and oxidative stress state. Furthermore, monitoring these metabolites could be a useful tool for predicting response to treatments. To our knowledge, there are no metabolomic studies that evaluated BC patients receiving CT and that included longitudinal monitoring to identify any changes in the metabolic profile induced by treatment.

Metabolic changes induced by T cell-mediated cutaneous vaccinia virus clearance

Abstract Viral infections induce prominent alterations to the host metabolism. Vaccinia virus (VACV) has been used as a live vaccine preventing smallpox and monkeypox. However, much remains unknown about the metabolic regulations of the adaptive immune response mounted to VACV infection in the skin. To survey the metabolic changes during VACV clearance, we performed a longitudinal metabolomics study based on our cutaneous VACV infection murine model. We adoptively transferred OT-I CD8 +T cells into Rag−/−mice, then infected one ear with VACV expressing SIINFEKL and VACV lacking SIINFEKL in the contralateral ear. Ears were harvested on 0,5,6,7,8,10 days post infection (dpi), which were homogenized and methanol extracted prior to untargeted mass spectrometry analyses. Metabolomics profiling revealed that VACV infection induced significant metabolic changes over time in the ear tissue. Interestingly, the metabolic profile after viral clearance was still distinct from uninfected control group. The levels of phenylalanine (adj. p=0.032), oleic acid (adj. p=0.011), S-lactoylglutathione (adj. p=0.022), and hypoxanthine (adj. p=0.039) were significantly altered between samples undergoing T cells-mediated killing and those without. Furthermore, glutamic acid level was significantly different (adj. p=0.036) between groups with and without T cells, suggesting T cell utilization during VACV clearance. Overall, our results indicated that VACV infection caused significant and persistent metabolic perturbation in the skin tissue environment. Antiviral T cells that mediate VACV clearance may require specific metabolites or metabolic pathways to regulate cytotoxic functions.