PubMed

Geroscience. 2024 Feb 24. doi: 10.1007/s11357-024-01101-7. Online ahead of print.ABSTRACTThe World Health Organization recently declared 2021-2030 the decade of healthy aging. Such emphasis on healthy aging requires an understanding of the biologic challenges aging populations face. Physical frailty is a syndrome of vulnerability that puts a subset of older adults at high risk for adverse health outcomes including functional and cognitive decline, falls, hospitalization, and mortality. The physiology driving physical frailty is complex with age-related biological changes, dysregulated stress response systems, chronic inflammatory pathway activation, and altered energy metabolism all likely contributing. Indeed, a series of recent studies suggests circulating metabolomic distinctions can be made between frail and non-frail older adults. For example, marked restrictions on glycolytic and mitochondrial energy production have been independently observed in frail older adults and collectively appear to yield a reliance on the highly fatigable ATP-phosphocreatine (PCr) energy system. Further, there is evidence that age-associated impairments in the primary ATP generating systems (glycolysis, TCA cycle, electron transport) yield cumulative deficits and fail to adequately support the ATP-PCr system. This in turn may acutely contribute to several major components of the physical frailty phenotype including muscular fatigue, weakness, slow walking speed and, over time, result in low physical activity and accelerate reductions in lean body mass. This review describes specific age-associated metabolic declines and how they can collectively lead to metabolic inflexibility, ATP-PCr reliance, and the development of physical frailty. Further investigation remains necessary to understand the etiology of age-associated metabolic deficits and develop targeted preventive strategies that maintain robust metabolic health in older adults.PMID:38400874 | DOI:10.1007/s11357-024-01101-7

Biomol Biomed. 2024 Feb 23. doi: 10.17305/bb.2024.10098. Online ahead of print.ABSTRACTPediatric renal diseases encompass a diverse array of pathological conditions, often engendering enduring ramifications. Metabolomics, an emergent branch of omics sciences, endeavors to holistically delineate alterations in metabolite compositions through the amalgamation of sophisticated analytical chemistry techniques and robust statistical methodologies. Recent advancements in metabolomics research within the realm of pediatric nephrology have been substantial, offering promising avenues for the identification of robust biomarkers, the elaboration of novel therapeutic targets, and the intricate elucidation of molecular mechanisms. The present discourse aims to critically review the progress in metabolomics profiling pertinent to pediatric renal disorders over the previous 12 years.PMID:38400839 | DOI:10.17305/bb.2024.10098

Ann Neurol. 2024 Feb 24. doi: 10.1002/ana.26894. Online ahead of print.ABSTRACTOBJECTIVE: Patients with Alzheimer's disease (AD) have diffuse brain atrophy, but some regions, such as the anterior cingulate cortex (ACC), are spared and may even show increase in size compared to controls. The extent, clinical significance, and mechanisms associated with increased cortical thickness in AD remain unknown. Recent work suggested neural facilitation of regions anticorrelated to atrophied regions in frontotemporal dementia. Here, we aim to determine whether increased thickness occurs in sporadic AD, whether it relates to clinical symptoms, and whether it occur in brain regions functionally connected to-but anticorrelated with-locations of atrophy.METHODS: Cross-sectional clinical, neuropsychological, and neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative were analyzed to investigate cortical thickness in AD subjects versus controls. Atrophy network mapping was used to identify brain regions functionally connected to locations of increased thickness and atrophy.RESULTS: AD patients showed increased thickness in the ACC in a region-of-interest analysis and the visual cortex in an exploratory analysis. Increased thickness in the left ACC was associated with preserved cognitive function, while increased thickness in the left visual cortex was associated with hallucinations. Finally, we found that locations of increased thickness were functionally connected to, but anticorrelated with, locations of brain atrophy (r = -0.81, p < 0.05).INTERPRETATION: Our results suggest that increased cortical thickness in Alzheimer's disease is relevant to AD symptoms and preferentially occur in brain regions functionally connected to, but anticorrelated with, areas of brain atrophy. Implications for models of compensatory neuroplasticity in response to neurodegeneration are discussed. ANN NEUROL 2024.PMID:38400760 | DOI:10.1002/ana.26894

Transfusion. 2024 Feb 23. doi: 10.1111/trf.17756. Online ahead of print.ABSTRACTBACKGROUND: Donor genetic variation is associated with red blood cell (RBC) storage integrity and post-transfusion recovery. Our previous large-scale genome-wide association study demonstrated that the African G6PD deficient A- variant (rs1050828, Val68Met) is associated with higher oxidative hemolysis after cold storage. Despite a high prevalence of X-linked G6PD mutation in African American population (>10%), blood donors are not routinely screened for G6PD status and its importance in transfusion medicine is relatively understudied.STUDY DESIGN AND METHODS: To further evaluate the functional effects of the G6PD A- mutation, we created a novel mouse model carrying this genetic variant using CRISPR-Cas9. We hypothesize that this humanized G6PD A- variant is associated with reduced G6PD activity with a consequent effect on RBC hemolytic propensity and post-transfusion recovery.RESULTS: G6PD A- RBCs had reduced G6PD protein with ~5% residual enzymatic activity. Significantly increased in vitro hemolysis induced by oxidative stressors was observed in fresh and stored G6PD A- RBCs, along with a lower GSH:GSSG ratio. However, no differences were observed in storage hemolysis, osmotic fragility, mechanical fragility, reticulocytes, and post-transfusion recovery. Interestingly, a 14% reduction of 24-h survival following irradiation was observed in G6PD A- RBCs compared to WT RBCs. Metabolomic assessment of stored G6PD A- RBCs revealed an impaired pentose phosphate pathway (PPP) with increased glycolytic flux, decreasing cellular antioxidant capacity.DISCUSSION: This novel mouse model of the common G6PD A- variant has impaired antioxidant capacity like humans and low G6PD activity may reduce survival of transfused RBCs when irradiation is performed.PMID:38400625 | DOI:10.1111/trf.17756

Viruses. 2024 Feb 19;16(2):313. doi: 10.3390/v16020313.ABSTRACTHIV-exposed, uninfected (HEU) children present with suboptimal growth and a greater susceptibility to infection in early life when compared to HIV-unexposed, uninfected (HUU) children. The reasons for these findings are poorly understood. We used a metabolomics approach to investigate the metabolic differences between pregnant women living with HIV (PWLWH) and their HEU infants compared to the uninfected and unexposed controls. Untargeted metabolomic profiling was performed using 1H-NMR spectroscopy on maternal plasma at 28 weeks' gestation and infant plasma at birth, 6/10 weeks, and 6 months. PWLWH were older but, apart from a larger 28 week mid-upper-arm circumference, anthropometrically similar to the controls. At all the time points, HEU infants had a significantly reduced growth compared to HUU infants. PWLWH had lower plasma 3-hydroxybutyric acid, acetoacetic acid, and acetic acid levels. In infants at birth, threonine and myo-inositol levels were lower in the HEU group while formic acid levels were higher. At 6/10 weeks, betaine and tyrosine levels were lower in the HEU group. Finally, at six months, 3-hydroxyisobutyric acid levels were lower while glycine levels were higher in the HEU infants. The NMR analysis has provided preliminary information indicating differences between HEU and HUU infants' plasma metabolites involved in energy utilization, growth, and protection from infection.PMID:38400088 | DOI:10.3390/v16020313

Viruses. 2024 Jan 31;16(2):218. doi: 10.3390/v16020218.ABSTRACTMost plants have developed unique mechanisms to cope with harsh environmental conditions to compensate for their lack of mobility. A key part of their coping mechanisms is the synthesis of secondary metabolites. In addition to their role in plants' defense against pathogens, they also possess therapeutic properties against diseases, and their use by humans predates written history. Viruses are a unique class of submicroscopic agents, incapable of independent existence outside a living host. Pathogenic viruses continue to pose a significant threat to global health, leading to innumerable fatalities on a yearly basis. The use of medicinal plants as a natural source of antiviral agents has been widely reported in literature in the past decades. Metabolomics is a powerful research tool for the identification of plant metabolites with antiviral potentials. It can be used to isolate compounds with antiviral capacities in plants and study the biosynthetic pathways involved in viral disease progression. This review discusses the use of medicinal plants as antiviral agents, with a special focus on the metabolomics evidence supporting their efficacy. Suggestions are made for the optimization of various metabolomics methods of characterizing the bioactive compounds in plants and subsequently understanding the mechanisms of their operation.PMID:38399995 | DOI:10.3390/v16020218

Microorganisms. 2024 Feb 19;12(2):413. doi: 10.3390/microorganisms12020413.ABSTRACTThe discovery of new natural products has become more challenging because of the re-isolation of compounds and the lack of new sources. Microbes dwelling in extreme conditions of high salinity and temperature are huge prospects for interesting natural metabolites. In this study, the endophytic bacteria Bacillus velezensis 7NPB-3B isolated from the halophyte Salicornia brachiata was screened for its biofilm inhibition against methicillin-resistant Staphylococcus aureus (MRSA). The fractionation of the crude extract was guided by bioassay and LC-HRMS-based metabolomics using multivariate analysis. The 37 fractions obtained by high-throughput chromatography were dereplicated using an in-house MS-Excel macro coupled with the Dictionary of Natural Products database. Successive bioactivity-guided separation yielded one novel compound (1), a diketopiperazine (m/z 469.258 [M - H]-) with an attached saturated decanoic acid chain, and four known compounds (2-5). The compounds were identified based on 1D- and 2D-NMR and mass spectrometry. Compounds 1 and 5 exhibited excellent biofilm inhibition properties of >90% against the MRSA pathogen at minimum inhibition concentrations of 25 and 35 µg/mL, respectively. The investigation resulted in the isolation of a novel diketopiperazine from a bacterial endophyte of an untapped plant using an omics approach.PMID:38399817 | DOI:10.3390/microorganisms12020413

Microorganisms. 2024 Feb 17;12(2):405. doi: 10.3390/microorganisms12020405.ABSTRACTFungal-bacterial combinations have a significant role in increasing and improving plant health under various stress conditions. Metabolites secreted by fungi and bacteria play an important role in this process. Our study emphasizes the significance of secondary metabolites secreted by the fungus Serendipita indica alone and by an actinobacterium Zhihengliuella sp. ISTPL4 under normal growth conditions and arsenic (As) stress condition. Here, we evaluated the arsenic tolerance ability of S. indica alone and in combination with Z. sp. ISTPL4 under in vitro conditions. The growth of S. indica and Z. sp. ISTPL4 was measured in varying concentrations of arsenic and the effect of arsenic on spore size and morphology of S. indica was determined using confocal microscopy and scanning electron microscopy. The metabolomics study indicated that S. indica alone in normal growth conditions and under As stress released pentadecanoic acid, glycerol tricaprylate, L-proline and cyclo(L-prolyl-L-valine). Similarly, d-Ribose, 2-deoxy-bis(thioheptyl)-dithioacetal were secreted by a combination of S. indica and Z. sp. ISTPL4. Confocal studies revealed that spore size of S. indica decreased by 18% at 1.9 mM and by 15% when in combination with Z. sp. ISTPL4 at a 2.4 mM concentration of As. Arsenic above this concentration resulted in spore degeneration and hyphae fragmentation. Scanning electron microscopy (SEM) results indicated an increased spore size of S. indica in the presence of Z. sp. ISTPL4 (18 ± 0.75 µm) compared to S. indica alone (14 ± 0.24 µm) under normal growth conditions. Our study concluded that the suggested combination of microbial consortium can be used to increase sustainable agriculture by combating biotic as well as abiotic stress. This is because the metabolites released by the microbial combination display antifungal and antibacterial properties. The metabolites, besides evading stress, also confer other survival strategies. Therefore, the choice of consortia and combination partners is important and can help in developing strategies for coping with As stress.PMID:38399809 | DOI:10.3390/microorganisms12020405

Microorganisms. 2024 Feb 2;12(2):317. doi: 10.3390/microorganisms12020317.ABSTRACTThe urgency of responding to climate change for corals necessitates the exploration of innovative methods to swiftly enhance our understanding of crucial processes. In this study, we employ an integrated chemical omics approach, combining elementomics, metabolomics, and volatilomics methodologies to unravel the biochemical pathways associated with the thermal response of the coral symbiont, Symbiodiniaceae Durusdinium trenchii. We outline the complimentary sampling approaches and discuss the standardised data corrections used to allow data integration and comparability. Our findings highlight the efficacy of individual methods in discerning differences in the biochemical response of D. trenchii under both control and stress-inducing temperatures. However, a deeper insight emerges when these methods are integrated, offering a more comprehensive understanding, particularly regarding oxidative stress pathways. Employing correlation network analysis enhanced the interpretation of volatile data, shedding light on the potential metabolic origins of volatiles with undescribed functions and presenting promising candidates for further exploration. Elementomics proves to be less straightforward to integrate, likely due to no net change in elements but rather elements being repurposed across compounds. The independent and integrated data from this study informs future omic profiling studies and recommends candidates for targeted research beyond Symbiodiniaceae biology. This study highlights the pivotal role of omic integration in advancing our knowledge, addressing critical gaps, and guiding future research directions in the context of climate change and coral reef preservation.PMID:38399721 | DOI:10.3390/microorganisms12020317

Microorganisms. 2024 Jan 30;12(2):292. doi: 10.3390/microorganisms12020292.ABSTRACTVulvovaginal candidiasis (VVC) is a common gynecologic disorder caused by fungal infections of the vaginal mucosa, with the most common pathogen being Candida albicans (C. albicans). Exploring metabolite changes in the disease process facilitates further discovery of targets for disease treatment. However, studies on the metabolic changes caused by C. albicans are still lacking. In this study, we used C. albicans-infected vaginal epithelial cells to construct an in vitro model of VVC, analyzed the metabolites by UHPLC-Q-Exactive MS, and screened the potential metabolites based on metabolomics. The results showed that C. albicans infection resulted in significant up-regulation of D-arabitol, palmitic acid, adenosine, etc.; significant down-regulation of lactic acid, nicotinamide (NAM), nicotinate (NA), etc.; and disruption of amino acid metabolism, and that these significantly altered metabolites might be potential therapeutic targets of VVC. Further experiments showed that C. albicans infection led to a decrease in glycolytic enzymes in damaged cells, inhibiting glycolysis and leading to significant alterations in glycolytic metabolites. The present study explored the potential metabolites of VVC induced by C. albicans infection based on metabolomics and verified the inhibitory effect of C. albicans on vaginal epithelial cell glycolysis, which is valuable for the diagnosis and treatment of VVC.PMID:38399696 | DOI:10.3390/microorganisms12020292

Nutrients. 2024 Feb 8;16(4):492. doi: 10.3390/nu16040492.ABSTRACTObjective: the aim of this study was to identify plasma metabolomic markers of Dietary Approaches to Stop Hypertension (DASH) dietary patterns in pregnant women. Methods: This study included 186 women who had both dietary intake and metabolome measured from a nested case-control study within the NICHD Fetal Growth Studies-Singletons cohort (FGS). Dietary intakes were ascertained at 8-13 gestational weeks (GW) using the Food Frequency Questionnaire (FFQ) and DASH scores were calculated based on eight food and nutrient components. Fasting plasma samples were collected at 15-26 GW and untargeted metabolomic profiling was performed. Multivariable linear regression models were used to examine the association of individual metabolites with the DASH score. Least absolute shrinkage and selection operator (LASSO) regression was used to select a panel of metabolites jointly associated with the DASH score. Results: Of the total 460 known metabolites, 92 were individually associated with DASH score in linear regressions, 25 were selected as a panel by LASSO regressions, and 18 were identified by both methods. Among the top 18 metabolites, there were 11 lipids and lipid-like molecules (i.e., TG (49:1), TG (52:2), PC (31:0), PC (35:3), PC (36:4) C, PC (36:5) B, PC (38:4) B, PC (42:6), SM (d32:0), gamma-tocopherol, and dodecanoic acid), 5 organic acids and derivatives (i.e., asparagine, beta-alanine, glycine, taurine, and hydroxycarbamate), 1 organic oxygen compound (i.e., xylitol), and 1 organoheterocyclic compound (i.e., maleimide). Conclusions: our study identified plasma metabolomic markers for DASH dietary patterns in pregnant women, with most of being lipids and lipid-like molecules.PMID:38398816 | DOI:10.3390/nu16040492

Nutrients. 2024 Feb 7;16(4):483. doi: 10.3390/nu16040483.ABSTRACTNormal pregnancy involves numerous physiological changes, including changes in hormone levels, immune responses, and metabolism. Although several studies have shown that the gut microbiota may have an important role in the progression of pregnancy, these findings have been inconsistent, and the relationship between the gut microbiota and metabolites that change dynamically during and after pregnancy remains to be clarified. In this longitudinal study, we comprehensively profiled the temporal dynamics of the gut microbiota, Bifidobacterium communities, and serum and faecal metabolomes of 31 women during their pregnancies and postpartum periods. The microbial composition changed as gestation progressed, with the pregnancy and postpartum periods exhibiting distinct bacterial community characteristics, including significant alterations in the genera of the Lachnospiraceae or Ruminococcaceae families, especially the Lachnospiraceae FCS020 group and Ruminococcaceae UCG-003. Metabolic dynamics, characterised by changes in nutrients important for fetal growth (e.g., docosatrienoic acid), anti-inflammatory metabolites (e.g., trans-3-indoleacrylic acid), and steroid hormones (e.g., progesterone), were observed in both serum and faecal samples during pregnancy. Moreover, a complex correlation was identified between the pregnancy-related microbiota and metabolites, with Ruminococcus1 and Ruminococcaceae UCG-013 making important contributions to changes in faecal and serum metabolites, respectively. Overall, a highly coordinated microbiota-metabolite regulatory network may underlie the pregnancy process. These findings provide a foundation for enhancing our understanding of the molecular processes occurring during the progression of pregnancy, thereby contributing to nutrition and health management during this period.PMID:38398806 | DOI:10.3390/nu16040483

Life (Basel). 2024 Jan 24;14(2):174. doi: 10.3390/life14020174.ABSTRACTThe present study aims to elucidate the metabolomic profile of Arthrospira platensis grown in a bioreactor in Bulgaria. The results show that Arthrospira platensis has a high content of mannose, 137.02 mg g-1, and vitamin A (retinol)-10.3 μg/100 g. High concentrations of calcium, sulfur, and zinc distinguish its elemental composition. The freeze-dried powder contained 15.81 ± 0.45% dietary fiber, 50.16 ± 0.25% total protein content, and 1.22 ± 0.11% total fat content. Among the unsaturated fatty acids with the highest content is α-linolenic acid (25.28%), while among the saturated fatty acids, palmitic acid prevails (22.55%). Of the sterols in the sample, β-sitosterol predominated. There is no presence of microcystins LR, RR, YR, and nodularin. Therefore, Arthrospira platensis grown in a Bulgarian bioreactor is safe for use in the pharmaceutical and food industries. Many of the organic compounds found have applications in medicine and pharmacology and play an important role in biochemical processes in the body. Therefore, Arthrospira platensis grown in Bulgaria has a high potential for use as an independent food supplement or in combination with other natural products.PMID:38398682 | DOI:10.3390/life14020174

Molecules. 2024 Feb 15;29(4):860. doi: 10.3390/molecules29040860.ABSTRACTBistorta vivipara is a medicinal plant with a long history, but there are few studies on the effects of its medicinal components and endophytic bacteria on the accumulation of secondary metabolites. Therefore, in this study, non-targeted metabolomics techniques and 16s rDNA techniques were used to study B. vivipara from different regions. A total of 1290 metabolites and 437 differential metabolites were identified from all samples. Among them, flavonoids, isoflavonoids, and benzopyrans are the main medicinal components of B. vivipara; these have potential anticancer, antiviral, and antioxidant properties, as well as potential applications for the treatment of atrial fibrillation. In addition, irigenin, an important medicinal component, was identified for the first time. The endophytic bacterial communities in the root tissues of B. vivipara from different regions were also different in composition and richness. Hierarchical clustering heat map analysis showed that Proteobacteria and Actinobacteriota bacteria significantly affected the accumulation of many medicinal components in the roots of B. vivipara.PMID:38398612 | DOI:10.3390/molecules29040860

J Clin Med. 2024 Feb 6;13(4):927. doi: 10.3390/jcm13040927.ABSTRACTBackground: Functional gastrointestinal disorders are very common condition. The aim of this study is to evaluate the implications of the mode of pregnancy termination and early infant feeding on the incidence of gastrointestinal disorders and atopic dermatitis at birth and 3, 6, and 12 months of age. Methods: This study included 82 pregnant women and their newborns born at term. All newborns were examined at birth and 3, 6, and 12 months of age according to the ROME IV criteria. Results: In children born after cesarean section, the incidence of regurgitation was significantly higher. In children fed mostly or exclusively with formula, dry skin with allergic features was observed more often compared to breastfed children, but this relation was statistically significant only at the age of 12 months. The use of antibiotic therapy increased the risk of allergic skin lesions by almost seven times at 3 months of life. Gastrointestinal disorders in the form of regurgitation, colic, and constipation occur within the period of up to 12 months of the child's life and may be related to the mode of the termination of pregnancy via cesarean section and the use of artificial feeding or antibiotic therapy. The occurrence of atopic dermatitis in infants at 12 months of life is correlated with the mode of the termination of pregnancy after cesarean section. Conclusions: One of the risk factors for the occurrence of atopic dermatitis and gastrointestinal disorders in the period up to 12 months of the child's life may be a cesarean section and the use of formula feeding or antibiotic therapy.PMID:38398241 | DOI:10.3390/jcm13040927

Biomedicines. 2024 Feb 6;12(2):380. doi: 10.3390/biomedicines12020380.ABSTRACTINTRODUCTION AND PURPOSE: Bicuspid aortic valve (BAV) disease is associated with faster aortic valve degeneration and a high incidence of aortic stenosis (AS). In this study, we aimed to identify differences in the pathophysiology of AS between BAV and tricuspid aortic valve (TAV) patients in a multiomics study integrating metabolomics and transcriptomics as well as clinical data.METHODS: Eighteen patients underwent aortic valve replacement due to severe aortic stenosis: 8 of them had a TAV, while 10 of them had a BAV. RNA sequencing (RNA-seq) and proton nuclear magnetic resonance spectroscopy (1H-NMR) were performed on these tissue samples to obtain the RNA profile and lipid and low-molecular-weight metabolites. These results combined with clinical data were posteriorly compared, and a multiomic profile specific to AS in BAV disease was obtained.RESULTS: H-NMR results showed that BAV patients with AS had different metabolic profiles than TAV patients. RNA-seq also showed differential RNA expression between the groups. Functional analysis helped connect this RNA pattern to mitochondrial dysfunction. Integration of RNA-seq, 1H-NMR and clinical data helped create a multiomic profile that suggested that mitochondrial dysfunction and oxidative stress are key players in the pathophysiology of AS in BAV disease.CONCLUSIONS: The pathophysiology of AS in BAV disease differs from patients with a TAV and has a specific RNA and metabolic profile. This profile was associated with mitochondrial dysfunction and increased oxidative stress.PMID:38397982 | DOI:10.3390/biomedicines12020380

Biomedicines. 2024 Jan 29;12(2):315. doi: 10.3390/biomedicines12020315.ABSTRACTSome studies have investigated the potential role of transposable elements (TEs) in COVID-19 pathogenesis and complications. However, to the best of our knowledge, there is no study to examine the possible association of TE expression in cell functions and its potential role in COVID-19 immune response at the single-cell level. In this study, we reanalyzed single-cell RNA seq data of bronchoalveolar lavage (BAL) samples obtained from six severe COVID-19 patients and three healthy donors to assess the probable correlation of TE expression with the immune responses induced by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in COVID-19 patients. Our findings indicate that the expansion of myeloid-derived suppressor cells (MDSCs) may be a characteristic feature of COVID-19. Additionally, a significant increase in TE expression in MDSCs was observed. This upregulation of TEs in COVID-19 may be linked to the adaptability of these cells in response to their microenvironments. Furthermore, it appears that the identification of overexpressed TEs by pattern recognition receptors (PRRs) in MDSCs may enhance the suppressive capacity of these cells. Thus, this study emphasizes the crucial role of TEs in the functionality of MDSCs during COVID-19.PMID:38397917 | DOI:10.3390/biomedicines12020315

Biomedicines. 2024 Jan 27;12(2):300. doi: 10.3390/biomedicines12020300.ABSTRACTGout results from monosodium urate deposition caused by hyperuricemia, but most individuals with hyperuricemia remain asymptomatic. The pathogenesis of gout remains uncertain. To identify potential biomarkers distinguishing gout from asymptomatic hyperuricemia, we conducted a genetic analysis of urate transporters and metabolomic analysis as a proof-of-concept study, including 33 patients with gout and 9 individuals with asymptomatic hyperuricemia. The variant allele frequencies of rs72552713, rs2231142, and rs3733591, which are related to serum urate levels (SUA) and gout, did not differ between the gout and asymptomatic hyperuricemia groups. In metabolomic analysis, the levels of citrate cycle intermediates, especially 2-ketoglutarate, were higher in patients with gout than in those with asymptomatic hyperuricemia (fold difference = 1.415, p = 0.039). The impact on the TCA cycle was further emphasized in high-risk gout (SUA ≥ 9.0 mg/dL). Of note, urinary nicotinate was the most prominent biomarker differentiating high-risk gout from asymptomatic hyperuricemia (fold difference = 6.515, p = 0.020). Although urate transporters play critical roles in SUA elevation and promote hyperuricemia, this study suggests that the progression from asymptomatic hyperuricemia to gout might be closely related to other genetic and/or environmental factors affecting carbohydrate metabolism and urinary urate excretion.PMID:38397902 | DOI:10.3390/biomedicines12020300

Antioxidants (Basel). 2024 Feb 19;13(2):253. doi: 10.3390/antiox13020253.ABSTRACTSows suffer oxidative stress and inflammation induced by metabolic burden during late pregnancy, which negatively regulates reproductive and lactating performances. We previously found that L-malic acid (MA) alleviated oxidative stress and inflammation and improved reproductive performances in sows. However, the mechanism underlying the MA's positive effects remains unexplored. Here, twenty Large White × Landrace sows with similar parity were randomly divided into two groups and fed with a basal diet or a diet supplemented with 2% L-malic acid complex from day 85 of gestation to delivery. The gut microbiome, fecal short-chain fatty acids, and untargeted serum metabolome were determined. Results showed that Firmicutes, Bacteroidota, and Spirochaetota were the top abundant phyla identified in late pregnancy for sows. Maternal MA supplementation modulated the composition but not the richness and diversity of gut microbiota during late pregnancy. Correlation analysis between gut microbiota and antioxidant capacity (or inflammation indicators) revealed that unclassified_f_Ruminococcaceae, unclassified_f_Lachnospiraceae, UCG-002, norank_f_norank_o_RF3, and Lactobacillus might play a role in anti-oxidation, and Lachnospiraceae_XPB1014_group, Lachnospiraceae_NK4A136_group, UCG-002, unclassified_f_Ruminococcaceae, Candidatus_Soleaferrea, norank_f_UCG-010, norank_f_norank_o_RF39, and unclassified_f_Lachnospiraceae might be involved in the anti-inflammatory effect. The improved antioxidant and inflammation status induced by MA might be independent of short chain fatty acid changes. In addition, untargeted metabolomics analysis exhibited different metabolic landscapes of sows in the MA group from in the control group and revealed the contribution of modified amino acid and lipid metabolism to the improved antioxidant capacity and inflammation status. Notably, correlation results of gut microbiota and serum metabolites, as well as serum metabolites and antioxidant capacity (or inflammation indicators), demonstrated that differential metabolism was highly related to the fecal microorganisms and antioxidant or inflammation indicators. Collectively, these data demonstrated that a maternal dietary supply of MA can ameliorate oxidative stress and inflammation in sows through modulating gut microbiota and host metabolic profiles during late pregnancy.PMID:38397851 | DOI:10.3390/antiox13020253

Antioxidants (Basel). 2024 Feb 18;13(2):243. doi: 10.3390/antiox13020243.ABSTRACTCitrus is an important type of fruit, with antioxidant bioactivity. However, the variations in the antioxidant ability of different tissues in citrus and its metabolic and molecular basis remain unclear. Here, we assessed the antioxidant capacities of 12 tissues from Citrus reticulata 'Ponkan', finding that young leaves and root exhibited the strongest antioxidant capacity. Secondary metabolites accumulated differentially in parts of the citrus plant, of which flavonoids were enriched in stem, leaf, and flavedo; phenolic acids were enriched in the albedo, while coumarins were enriched in the root, potentially explaining the higher antioxidant capacities of these tissues. The spatially specific accumulation of metabolites was related to the expression levels of biosynthesis-related genes such as chalcone synthase (CHS), chalcone isomerase (CHI), flavone synthase (FNS), O-methyltransferase (OMT), flavonoid-3'-hydroxylase (F3'H), flavonoid-6/8-hydroxylase (F6/8H), p-coumaroyl CoA 2'-hydroxylase (C2'H), and prenyltransferase (PT), among others, in the phenylpropane pathway. Weighted gene co-expression network analysis (WGCNA) identified modules associated with flavonoids and coumarin content, among which we identified an OMT involved in coumarin O-methylation, and related transcription factors were predicted. Our study identifies key genes and metabolites influencing the antioxidant capacity of citrus, which could contribute to the enhanced understanding and utilization of bioactive citrus components.PMID:38397841 | DOI:10.3390/antiox13020243