PubMed

Metabolites. 2023 Aug 20;13(8):963. doi: 10.3390/metabo13080963.ABSTRACTApproximately 25% of psoriasis patients have an inflammatory arthritis termed psoriatic arthritis (PsA). There is strong interest in identifying and validating biomarkers that can accurately and reliably predict conversion from psoriasis to PsA using novel technologies such as metabolomics. Lipids, in particular, are of key interest in psoriatic disease. We sought to develop a liquid chromatography-mass spectrometry (LC-MS) method to be used in conjunction with solid-phase microextraction (SPME) for analyzing fatty acids and similar molecules. A total of 25 chromatographic methods based on published lipid studies were tested on two LC columns. As a proof of concept, serum samples from psoriatic disease patients (n = 27 psoriasis and n = 26 PsA) were processed using SPME and run on the selected LC-MS method. The method that was best for analyzing fatty acids and fatty acid-like molecules was optimized and applied to serum samples. A total of 18 tentatively annotated features classified as fatty acids and other lipid compounds were statistically significant between psoriasis and PsA groups using both multivariate and univariate approaches. The SPME-LC-MS method developed and optimized was capable of detecting fatty acids and similar lipids that may aid in differentiating psoriasis and PsA patients.PMID:37623906 | DOI:10.3390/metabo13080963

Metabolites. 2023 Aug 19;13(8):962. doi: 10.3390/metabo13080962.ABSTRACTGas chromatography-mass spectrometry (GC-MS) usually employs hard electron ionization, leading to extensive fragmentations that are suitable to identify compounds based on library matches. However, such spectra are less useful to structurally characterize unknown compounds that are absent from libraries, due to the lack of readily recognizable molecular ion species. We tested methane chemical ionization on 369 trimethylsilylated (TMS) derivatized metabolites using a quadrupole time-of-flight detector (QTOF). We developed an algorithm to automatically detect molecular ion species and tested SIRIUS software on how accurate the determination of molecular formulas was. The automatic workflow correctly recognized 289 (84%) of all 345 detected derivatized standards. Specifically, strong [M - CH3]+ fragments were observed in 290 of 345 derivatized chemicals, which enabled the automatic recognition of molecular adduct patterns. Using Sirius software, correct elemental formulas were retrieved in 87% of cases within the top three hits. When investigating the cases for which the automatic pattern analysis failed, we found that several metabolites showed a previously unknown [M + TMS]+ adduct formed by rearrangement. Methane chemical ionization with GC-QTOF mass spectrometry is a suitable avenue to identify molecular formulas for abundant unknown peaks.PMID:37623905 | DOI:10.3390/metabo13080962

Metabolites. 2023 Aug 18;13(8):961. doi: 10.3390/metabo13080961.ABSTRACTHuntington's disease (HD) is caused by the expansion of a polyglutamine (polyQ)-encoding tract in exon 1 of the huntingtin gene to greater than 35 CAG repeats. It typically has a disease course lasting 15-20 years, and there are currently no disease-modifying therapies available. Thus, there is a need for faithful mouse models of HD to use in preclinical studies of disease mechanisms, target validation, and therapeutic compound testing. A large variety of mouse models of HD were generated, none of which fully recapitulate human disease, complicating the selection of appropriate models for preclinical studies. Here, we present the urinary liquid chromatography-high-resolution mass spectrometry analysis employed to identify metabolic alterations in transgenic R6/2 and zQ175DN knock-in mice. In R6/2 mice, the perturbation of the corticosterone metabolism and the accumulation of pyrraline, indicative of the development of insulin resistance and the impairment of pheromone excretion, were observed. Differently from R6/2, zQ175DN mice showed the accumulation of oxidative stress metabolites. Both genotypes showed alterations in the tryptophan metabolism. This approach aims to improve our understanding of the molecular mechanisms involved in HD neuropathology, facilitating the selection of appropriate mouse models for preclinical studies. It also aims to identify potential biomarkers specific to HD.PMID:37623904 | DOI:10.3390/metabo13080961

Metabolites. 2023 Aug 18;13(8):960. doi: 10.3390/metabo13080960.ABSTRACTAge-related hepatic lipid accumulation has become a major health problem in the elderly population. Specnuezhenide (SPN) is a major active iridoid glycoside from an edible herb Fructus Ligustri Lucidi, which is commonly used for preventing age-related diseases. However, the beneficial effects of SPN on age-related liver injury remain unknown. This study aimed to reveal the effect of SPN on age-related hepatic lipid accumulation and the underlying mechanism. D-galactose (D-gal)-induced aging mice were treated with vehicle or SPN for 12 weeks. Treatment of SPN decreased lipid accumulation and inflammation in the liver of D-gal-induced mice. Untargeted and targeted metabolomics showed that the SPN could regulate the bile acid (BA) synthesis pathway and restore the BA compositions in serum, livers, and feces of the D-gal-induced mice. Furthermore, SPN enhanced the protein and mRNA levels of hepatic BAs synthesis enzymes cytochrome P45027A1, cytochrome P4507A1, cytochrome P4507B1, and cytochrome P4508B1. Meanwhile, SPN alleviated D-gal-induced gut dysbiosis and reversed the proportions of microbes associated with bile salt hydrolase activity, including Lactobacillus, Ruminiclostridium, and Butyrivibrio. Our study revealed that SPN attenuated age-related hepatic lipid accumulation by improving BA profiles via modulating hepatic BA synthesis enzymes and gut microbiota.PMID:37623903 | DOI:10.3390/metabo13080960

Metabolites. 2023 Aug 18;13(8):959. doi: 10.3390/metabo13080959.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been linked to changes in amino acid (AA) levels. The objective of the current study was to examine the relationship between MRI parameters that reflect inflammation and fibrosis and plasma AA concentrations in NAFLD patients. Plasma AA levels of 97 NAFLD patients from the MAST4HEALTH study were quantified with liquid chromatography. Medical, anthropometric and lifestyle characteristics were collected and biochemical parameters, as well as inflammatory and oxidative stress biomarkers, were measured. In total, subjects with a higher MRI-proton density fat fraction (MRI-PDFF) exhibited higher plasma AA levels compared to subjects with lower PDFF. The concentrations of BCAAs (p-Value: 0.03), AAAs (p-Value: 0.039), L-valine (p-Value: 0.029), L-tyrosine (p-Value: 0.039) and L-isoleucine (p-Value: 0.032) were found to be significantly higher in the higher PDFF group compared to lower group. Plasma AA levels varied according to MRI-PDFF. Significant associations were also demonstrated between AAs and MRI-PDFF and MRI-cT1, showing the potential utility of circulating AAs as diagnostic markers of NAFLD.PMID:37623902 | DOI:10.3390/metabo13080959

Metabolites. 2023 Aug 18;13(8):958. doi: 10.3390/metabo13080958.ABSTRACTLuria-Bertani broth (LB) culture medium is a commonly used bacterial culture medium in the laboratory. The nutrient composition, concentration, and culture conditions of LB medium can influence the growth of microbial strains. The purpose of this article is to demonstrate the impact of LB liquid culture medium on microbial growth under different sterilization conditions. In this study, LB medium with four different treatments was used, as follows: A, LB medium without treatments; B, LB medium with filtration; C, LB medium with autoclaving; and D, LB medium with autoclaving and cultured for 12 h. Subsequently, the protein levels and antioxidant capacity of the medium with different treatments were measured, and the effects of the different LB medium treatments on the growth of microorganisms and metabolites were determined via 16s rRNA gene sequencing and metabolomics analysis, respectively. Firmicutes and Lactobacillus were the dominant microorganisms, which were enriched in fermentation and chemoheterotrophy. The protein levels and antioxidant capacity of the LB medium with different treatments were different, and with the increasing concentration of medium, the protein levels were gradually increased, while the antioxidant capacity was decreased firstly and then increased. The growth trend of Bacillus subtilis, Bacillus paralicheniformis, Micrococcus luteus, and Alternaria alternata in the medium with different treatments was similar. Additionally, 220 and 114 differential metabolites were found between B and C medium, and between C and D medium, which were significantly enriched in the "Hedgehog signaling pathway", "biosynthesis of plant secondary metabolites", "ABC transporters", "arginine and proline metabolism", and "linoleic acid metabolism". LB medium may be a good energy source for Lactobacillus growth with unsterilized medium, and LB medium filtered with a 0.22 μm filter membrane may be used for bacterial culture better than culture medium after high-pressure sterilization. LB medium still has the ability for antioxidation and to keep bacteria growth whether or not autoclaved, indicating that there are some substances that can resist a high temperature and pressure and still maintain their functions.PMID:37623901 | DOI:10.3390/metabo13080958

Metabolites. 2023 Aug 18;13(8):953. doi: 10.3390/metabo13080953.ABSTRACTAging is the system-wide loss of homeostasis, eventually leading to death. There is growing evidence that the microbiome not only evolves with its aging host, but also directly affects aging via the modulation of metabolites involved in important cellular functions. The widely used model organism C. elegans exhibits high selectivity towards its native microbiome members which confer a range of differential phenotypes and possess varying functional capacities. The ability of one such native microbiome species, Chryseobacterium sp. CHNTR56 MYb120, to improve the lifespan of C. elegans and to promote the production of Vitamin B6 in the co-colonizing member Comamonas sp. 12022 MYb131 are some of its beneficial effects on the worm host. We hypothesize that studying its metabolic influence on the different life stages of the worm could provide further insights into mutualistic interactions. The present work applied LC-MS untargeted metabolomics and isotope labeling to study the impact of the native microbiome member Chryseobacterium sp. CHNTR56 MYb120 on the metabolism of C. elegans. In addition to the upregulation of biosynthesis and detoxification pathway intermediates, we found that Chryseobacterium sp. CHNTR56 MYb120 upregulates the glyoxylate shunt in mid-adult worms which is linked to the upregulation of trehalose, an important metabolite for desiccation tolerance in older worms.PMID:37623896 | DOI:10.3390/metabo13080953

Metabolites. 2023 Aug 16;13(8):951. doi: 10.3390/metabo13080951.ABSTRACTCOVID-19, a systemic multi-organ disease resulting from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is known to result in a wide array of disease outcomes, ranging from asymptomatic to fatal. Despite persistent progress, there is a continued need for more accurate determinants of disease outcomes, including post-acute symptoms after COVID-19. In this study, we characterised the serum metabolomic changes due to hospitalisation and COVID-19 disease progression by mapping the serum metabolomic trajectories of 71 newly hospitalised moderate and severe patients in their first week after hospitalisation. These 71 patients were spread out over three hospitals in Switzerland, enabling us to meta-analyse the metabolomic trajectories and filter consistently changing metabolites. Additionally, we investigated differential metabolite-metabolite trajectories between fatal, severe, and moderate disease outcomes to find prognostic markers of disease severity. We found drastic changes in serum metabolite concentrations for 448 out of the 901 metabolites. These results included markers of hospitalisation, such as environmental exposures, dietary changes, and altered drug administration, but also possible markers of physiological functioning, including carboxyethyl-GABA and fibrinopeptides, which might be prognostic for worsening lung injury. Possible markers of disease progression included altered urea cycle metabolites and metabolites of the tricarboxylic acid (TCA) cycle, indicating a SARS-CoV-2-induced reprogramming of the host metabolism. Glycerophosphorylcholine was identified as a potential marker of disease severity. Taken together, this study describes the metabolome-wide changes due to hospitalisation and COVID-19 disease progression. Moreover, we propose a wide range of novel potential biomarkers for monitoring COVID-19 disease course, both dependent and independent of the severity.PMID:37623894 | DOI:10.3390/metabo13080951

Metabolites. 2023 Aug 15;13(8):950. doi: 10.3390/metabo13080950.ABSTRACTThis review analyzed 21 scientific papers on the determination of amino acids in various types of cancer in saliva. Most of the studies are on oral cancer (8/21), breast cancer (4/21), gastric cancer (3/21), lung cancer (2/21), glioblastoma (2/21) and one study on colorectal, pancreatic, thyroid and liver cancer. The amino acids alanine, valine, phenylalanine, leucine and isoleucine play a leading role in the diagnosis of cancer via the saliva. In an independent version, amino acids are rarely used; the authors combine either amino acids with each other or with other metabolites, which makes it possible to obtain high values of sensitivity and specificity. Nevertheless, a logical and complete substantiation of the changes in saliva occurring in cancer, including changes in salivary amino acid levels, has not yet been formed, which makes it important to continue research in this direction.PMID:37623893 | DOI:10.3390/metabo13080950

Metabolites. 2023 Aug 15;13(8):948. doi: 10.3390/metabo13080948.ABSTRACTMetabolomics is an analytical approach that involves profiling and comparing the metabolites present in biological samples. This scoping review article offers an overview of current metabolomics approaches and their utilization in evaluating metabolic changes in biological fluids that occur in response to viral infections. Here, we provide an overview of metabolomics methods including high-throughput analytical chemistry and multivariate data analysis to identify the specific metabolites associated with viral infections. This review also focuses on data interpretation and applications designed to improve our understanding of the pathogenesis of these viral diseases.PMID:37623891 | DOI:10.3390/metabo13080948

Metabolites. 2023 Aug 15;13(8):947. doi: 10.3390/metabo13080947.ABSTRACTAlthough metabolic alterations are observed in many monogenic and complex genetic disorders, the impact of most mammalian genes on cellular metabolism remains unknown. Understanding the effect of mouse gene dysfunction on metabolism can inform the functions of their human orthologues. We investigated the effect of loss-of-function mutations in 30 unique gene knockout (KO) lines on plasma metabolites, including genes coding for structural proteins (11 of 30), metabolic pathway enzymes (12 of 30) and protein kinases (7 of 30). Steroids, bile acids, oxylipins, primary metabolites, biogenic amines and complex lipids were analyzed with dedicated mass spectrometry platforms, yielding 827 identified metabolites in male and female KO mice and wildtype (WT) controls. Twenty-two percent of 23,698 KO versus WT comparison tests showed significant genotype effects on plasma metabolites. Fifty-six percent of identified metabolites were significantly different between the sexes in WT mice. Many of these metabolites were also found to have sexually dimorphic changes in KO lines. We used plasma metabolites to complement phenotype information exemplified for Dhfr, Idh1, Mfap4, Nek2, Npc2, Phyh and Sra1. The association of plasma metabolites with IMPC phenotypes showed dramatic sexual dimorphism in wildtype mice. We demonstrate how to link metabolomics to genotypes and (disease) phenotypes. Sex must be considered as critical factor in the biological interpretation of gene functions.PMID:37623890 | DOI:10.3390/metabo13080947

Metabolites. 2023 Aug 15;13(8):946. doi: 10.3390/metabo13080946.ABSTRACTThis study aimed to determine the metabolic response of growing German Simmental bulls fed rations low in crude protein (CP) supplemented with rumen-protected methionine (RPMET). In total, 69 bulls (on average 238 ± 11 days of age at start and 367 ± 25 kg of bodyweight) were assigned to three dietary treatments (n = 23/group): Positive control (CON; 13.7% CP; 2.11 g methionine/kg DM), negative control deficient in CP (RED; 9.04% CP; 1.56 g methionine/kg DM) and crude protein-deficient ration supplemented with RPMET (RED+RPMET; 9.04% CP; 2.54 g methionine/kg DM). At slaughter, samples of liver, muscle and blood serum were taken and underwent subsequent metabolomics profiling using a UHPLC-QTOF-MS system. A total of 6540 features could be detected. Twenty metabolites in the liver, five metabolites in muscle and thirty metabolites in blood serum were affected (p < 0.05) due to dietary treatments. In total, six metabolites could be reliably annotated and were thus subjected to subsequent univariate analysis. Reduction in dietary CP had minimal effect on metabolite abundance in target tissues of both RED and RED+RPMET bulls as compared to CON bulls. The addition of RPMET altered the hepatic anti-oxidant status in RED+RPMET bulls compared to both RED and CON bulls. Results exemplify nutrient partitioning in growing German Simmental bulls: bulls set maintenance as the prevailing metabolic priority (homeostasis) and nutrient trafficking as the second priority, which was directed toward special metabolic functions, such as anti-oxidant pathways.PMID:37623889 | DOI:10.3390/metabo13080946

Metabolites. 2023 Aug 14;13(8):945. doi: 10.3390/metabo13080945.ABSTRACTThis article illustrates how dietary flaxseed can be used to reduce cancer risk, specifically by attenuating obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). We utilize a targeted metabolomics dataset in combination with a reanalysis of past work to investigate the "metabo-bioenergetic" adaptations that occur in White Leghorn laying hens while consuming dietary flaxseed. Recently, we revealed how the anti-vitamin B6 effects of flaxseed augment one-carbon metabolism in a manner that accelerates S-adenosylmethionine (SAM) biosynthesis. Researchers recently showed that accelerated SAM biosynthesis activates the cell's master energy sensor, AMP-activated protein kinase (AMPK). Our paper provides evidence that flaxseed upregulates mitochondrial fatty acid oxidation and glycolysis in liver, concomitant with the attenuation of lipogenesis and polyamine biosynthesis. Defatted flaxseed likely functions as a metformin homologue by upregulating hepatic glucose uptake and pyruvate flux through the pyruvate dehydrogenase complex (PDC) in laying hens. In contrast, whole flaxseed appears to attenuate liver steatosis and body mass by modifying mitochondrial fatty acid oxidation and lipogenesis. Several acylcarnitine moieties indicate Randle cycle adaptations that protect mitochondria from metabolic overload when hens consume flaxseed. We also discuss a paradoxical finding whereby flaxseed induces the highest glycated hemoglobin percentage (HbA1c%) ever recorded in birds, and we suspect that hyperglycemia is not the cause. In conclusion, flaxseed modifies bioenergetic pathways to attenuate the risk of obesity, type 2 diabetes, and NAFLD, possibly downstream of SAM biosynthesis. These findings, if reproducible in humans, can be used to lower cancer risk within the general population.PMID:37623888 | DOI:10.3390/metabo13080945

Metabolites. 2023 Aug 13;13(8):944. doi: 10.3390/metabo13080944.ABSTRACTLarge-scale metabolomics assays are widely used in epidemiology for biomarker discovery and risk assessments. However, systematic errors introduced by instrumental signal drifting pose a big challenge in large-scale assays, especially for derivatization-based gas chromatography-mass spectrometry (GC-MS). Here, we compare the results of different normalization methods for a study with more than 4000 human plasma samples involved in a type 2 diabetes cohort study, in addition to 413 pooled quality control (QC) samples, 413 commercial pooled plasma samples, and a set of 25 stable isotope-labeled internal standards used for every sample. Data acquisition was conducted across 1.2 years, including seven column changes. In total, 413 pooled QC (training) and 413 BioIVT samples (validation) were used for normalization comparisons. Surprisingly, neither internal standards nor sum-based normalizations yielded median precision of less than 30% across all 563 metabolite annotations. While the machine-learning-based SERRF algorithm gave 19% median precision based on the pooled quality control samples, external cross-validation with BioIVT plasma pools yielded a median 34% relative standard deviation (RSD). We developed a new method: systematic error reduction by denoising autoencoder (SERDA). SERDA lowered the median standard deviations of the training QC samples down to 16% RSD, yielding an overall error of 19% RSD when applied to the independent BioIVT validation QC samples. This is the largest study on GC-MS metabolomics ever reported, demonstrating that technical errors can be normalized and handled effectively for this assay. SERDA was further validated on two additional large-scale GC-MS-based human plasma metabolomics studies, confirming the superior performance of SERDA over SERRF or sum normalizations.PMID:37623887 | DOI:10.3390/metabo13080944

Metabolites. 2023 Aug 13;13(8):943. doi: 10.3390/metabo13080943.ABSTRACTMetabolomics is a method that provides an overview of the physiological and cellular state of a specific organism or tissue. This method is particularly useful for studying the influence the environment can have on organisms, especially those used as bio-indicators, e.g., Mytilus galloprovincialis. Nevertheless, a scarcity of data on the complete metabolic baseline of mussel tissues still exists, but more importantly, the effect of mussel exposure to certain heavy metals on spermatozoa is unknown, also considering that, in recent years, the reproductive system has proved to be very sensitive to the effects of environmental pollutants. In order to fill this knowledge gap, the similarities and differences in the metabolic profile of spermatozoa of mussels exposed to metallic chlorides of copper, nickel, and cadmium, and to the mixture to these metals, were studied using a metabolomics approach based on GC-MS analysis, and their physiological role was discussed. A total of 237 endogenous metabolites were identified in the spermatozoa of these mussel. The data underwent preprocessing steps and were analyzed using statistical methods such as PLS-DA. The results showed effective class separation and identified key metabolites through the VIP scores. Heatmaps and cluster analysis further evaluated the metabolites. The metabolite-set enrichment analysis revealed complex interactions within metabolic pathways and metabolites, especially involving glucose and central carbon metabolism and oxidative stress metabolism. Overall, the results of this study are useful to better understand how some pollutants can affect the specific physiological functions of the spermatozoa of this mussel, as well as for further GC-MS-based metabolomic health and safety studies of marine bivalves.PMID:37623886 | DOI:10.3390/metabo13080943

Metabolites. 2023 Aug 12;13(8):941. doi: 10.3390/metabo13080941.ABSTRACTMetabolomics has advanced to an extent where it is desired to standardize and compare data across individual studies. While past work in standardization has focused on data acquisition, data processing, and data storage aspects, metabolomics databases are useless without ontology-based descriptions of biological samples and study designs. We introduce here a user-centric tool to automatically standardize sample metadata. Using such a tool in frontends for metabolomic databases will dramatically increase the FAIRness (Findability, Accessibility, Interoperability, and Reusability) of data, specifically for data reuse and for finding datasets that share comparable sets of metadata, e.g., study meta-analyses, cross-species analyses or large scale metabolomic atlases. SMetaS (Sample Metadata Standardizer) combines a classic database with an API and frontend and is provided in a containerized environment. The tool has two user-centric components. In the first component, the user designs a sample metadata matrix and fills the cells using natural language terminology. In the second component, the tool transforms the completed matrix by replacing freetext terms with terms from fixed vocabularies. This transformation process is designed to maximize simplicity and is guided by, among other strategies, synonym matching and typographical fixing in an n-grams/nearest neighbors model approach. The tool enables downstream analysis of submitted studies and samples via string equality for FAIR retrospective use.PMID:37623884 | DOI:10.3390/metabo13080941

Metabolites. 2023 Aug 11;13(8):938. doi: 10.3390/metabo13080938.ABSTRACTAccording to studies, the microbiome may contribute to the emergence and spread of breast cancer. E. coli is one of the Enterobacteriaceae family recently found to be present as part of the breast tissue microbiota. In this study, we focused on the effect of E. coli secretome free of cells on MCF-7 metabolism. Liquid chromatography-mass spectrometry (LC-MS) metabolomics was used to study the E. coli secretome and its role in MCF-7 intra- and extracellular metabolites. A comparison was made between secretome-exposed cells and unexposed controls. Our analysis revealed significant alterations in 31 intracellular and 55 extracellular metabolites following secretome exposure. Several metabolic pathways, including lactate, aminoacyl-tRNA biosynthesis, purine metabolism, and energy metabolism, were found to be dysregulated upon E. coli secretome exposure. E. coli can alter the breast cancer cells' metabolism through its secretome which disrupts key metabolic pathways of MCF-7 cells. These microbial metabolites from the secretome hold promise as biomarkers of drug resistance or innovative approaches for cancer treatment, either as standalone therapies or in combination with other medicines.PMID:37623881 | DOI:10.3390/metabo13080938

Metabolites. 2023 Aug 9;13(8):932. doi: 10.3390/metabo13080932.ABSTRACTMost studies on single ventricle (SV) circulation take a physiological or anatomical approach. Although there is a tight coupling between cardiac contractility and metabolism, the metabolic perspective on this patient population is very recent. Early findings point to major metabolic disturbances, with both impaired glucose and fatty acid oxidation in the cardiomyocytes. Additionally, Fontan patients have systemic metabolic derangements such as abnormal glucose metabolism and hypocholesterolemia. Our literature review compares the metabolism of patients with a SV circulation after Fontan palliation with that of patients with a healthy biventricular (BV) heart, or different subtypes of a failing BV heart, by Pubmed review of the literature on cardiac metabolism, Fontan failure, heart failure (HF), ketosis, metabolism published in English from 1939 to 2023. Early evidence demonstrates that SV circulation is not only a hemodynamic burden requiring staged palliation, but also a metabolic issue with alterations similar to what is known for HF in a BV circulation. Alterations of fatty acid and glucose oxidation were found, resulting in metabolic instability and impaired energy production. As reported for patients with BV HF, stimulating ketone oxidation may be an effective treatment strategy for HF in these patients. Few but promising clinical trials have been conducted thus far to evaluate therapeutic ketosis with HF using a variety of instruments, including ketogenic diet, ketone esters, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. An initial trial on a small cohort demonstrated favorable outcomes for Fontan patients treated with SGLT2 inhibitors. Therapeutic ketosis is worth considering in the treatment of Fontan patients, as ketones positively affect not only the myocardial energy metabolism, but also the global Fontan physiopathology. Induced ketosis seems promising as a concerted therapeutic strategy.PMID:37623876 | DOI:10.3390/metabo13080932

Metabolites. 2023 Aug 8;13(8):928. doi: 10.3390/metabo13080928.ABSTRACTStress caused by noise is becoming widespread globally. Noise may lead to deafness, endocrine disorders, neurological diseases, and a decline in mental health. The mechanism behind noise-induced neurodevelopmental abnormalities is unclear, but apoptosis and pro-inflammatory signals may play an important role. In this study, weaned piglets were used as a model to explore noise-induced neurodevelopmental abnormalities. We hypothesized that long-term noise exposure would induce anxiety and cause acute stress, exhibited by alterations in neurotransmission in the amygdala. A total of 72 hybrid piglets (Large White × Duroc × Min Pig) were randomly divided into three groups, including noise (exposed to mechanical noise, 80-85 dB), control (blank, exposed to natural background sound, <40 dB), and music (positive control, exposed to Mozart K.448, 60-70 dB) groups. The piglets were exposed to 6 h of auditory noise daily (10:00-16:00) for 28 days. Compared with the control group, piglets exposed to noise showed more aggressive behavior. The expression of Caspase3, Caspase9, Bax, NF-κB (p56), TLR4, MYD88, I κ B α, IL-1 β, TNF-α, and IL-12RB2 was significantly upregulated in the amygdala, while the expression of Nrf2, HO-1, CAT, and SOD was downregulated in piglets in the noise group. Cell death occurred, and numerous inflammatory cells accumulated in the amygdala of piglets in the noise group. Targeted metabolomics showed that the content of inhibitory neurotransmitter GABA was higher in the amygdala of piglets in the noise group. Compared with the noise group, piglets in the music group displayed more positive emotion-related behaviors. Compared with the noise group, the expression of genes related to apoptosis, inflammation, and oxidative damage was lower in the music group. Cells of the amygdala in the music group were also of normal morphology. Our results show that noise-induced stress causes apoptosis and neuroinflammation in the amygdala and induces anxiety during the early neonatal neural development of piglets. In contrast, to some extent, music alleviates noise-induced anxiety.PMID:37623873 | DOI:10.3390/metabo13080928

Metabolites. 2023 Aug 8;13(8):929. doi: 10.3390/metabo13080929.ABSTRACTNon-alcoholic fatty liver disease is a multifaceted disease that progresses through multiple phases; it involves metabolic as well as structural changes. These alterations can be measured directly or indirectly through blood, non-invasive imaging, and/or tissue analyses. While some studies have evaluated the correlations between two sets of measurements (e.g., histopathology with cross-sectional imaging or blood biomarkers), the interrelationships, if any, among histopathology, clinical blood profiles, cross-sectional imaging, and metabolomics in a pediatric cohort remain unknown. We created a multiparametric clinical MRI-histopathologic NMR network map of pediatric NAFLD through multimodal correlation networks, in order to gain insight into how these different sets of measurements are related. We found that leptin and other blood markers were correlated with many other measurements; however, upon filtering out the blood biomarkers, the network was decomposed into three independent hubs centered around histopathological features, each with associated MRI and plasma metabolites. These multi-modality maps could serve as a framework for characterizing disease status and progression and could potentially guide medical interventions.PMID:37623872 | DOI:10.3390/metabo13080929