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Frontiers in Psychiatry 2023This study identified the metabolic biomarkers for different clinical phases of bipolar disorder (BD) through metabolomics. BD patients were divided into three groups:...
This study identified the metabolic biomarkers for different clinical phases of bipolar disorder (BD) through metabolomics. BD patients were divided into three groups: patients with BD and depressive episodes (BE, = 59), patients with BD and mania/hypomania episodes (BH, = 16), patients with BD and mixed episodes (BM, = 10), and healthy controls (HC, = 10). Serum from participants was collected for metabolomic sequencing, biomarkers from each group were screened separately by partial least squares analysis, and metabolic pathways connected to the biomarkers were identified. Compared with the controls, 3-D-hydroxyacetic acid and N-acetyl-glycoprotein showed significant differences in the BE, BH, and BM groups. This study suggests that different clinical types of BD share the same metabolic pathways, such as pyruvate, glycolysis/gluconeogenesis, and ketone body metabolisms. In particular, abnormal glycine, serine, and threonine metabolism was specific to BM; β-glucose, glycerol, lipids, lactate, and acetoacetate metabolites were specific to depressive episodes; the guanidine acetic acid metabolites specific to BH; and the acetic and ascorbic acids were metabolites specific to manic and BM. We screened potential biomarkers for different clinical phases of BD, which aids in BD typing and provides a theoretical basis for exploring the molecular mechanisms of BD.
PubMed: 38264633
DOI: 10.3389/fpsyt.2023.1319870 -
Metabolites Jan 2024Dysbiotic vaginal microbiota (DVM) disturb the vaginal environment, including pH, metabolite, protein, and cytokine profiles. This study investigated the impact of DVM...
Dysbiotic vaginal microbiota (DVM) disturb the vaginal environment, including pH, metabolite, protein, and cytokine profiles. This study investigated the impact of DVM on the vaginal environment in 40 Korean pregnant women and identified predictable biomarkers of birth outcomes. Cervicovaginal fluid (CVF) samples were collected in the third trimester using vaginal swabs, examined for pH, and stored at -80 °C for further analysis. The samples were grouped as full-term (FTB, n = 20) and preterm (PTB, n = 20) births. The microbiota was profiled in the V1-V9 regions. The levels of targeted metabolites, TLR-4, and cytokines were determined. The pH of CVF from PTB (>4.5) was significantly higher than that of the CVF from FTB (>3.5) ( < 0.05). Neonatal gestational age at delivery, birth weight, and Apgar score differed significantly between groups. The relative abundances of beneficial spp., such as , , and , were higher in FTB, whereas those of pathogenic , , , , and spp. were higher in PTB. Acetate, methanol, TLR-4, and TNF-α levels were negatively correlated with gestational age at delivery and birth weight. Moreover, ethanol, methanol, TLR-4, IL-6, IL-1β, and TNF-α levels were positively correlated with succinate, acetate, acetoacetate, formate, and ammonia. Overall, DVM induces preterm birth via pathogenic molecules in the vagina.
PubMed: 38248848
DOI: 10.3390/metabo14010045 -
Biosensors Dec 2023Ketones are well-known biomarkers of fat oxidation produced in the liver as a result of lipolysis. These biomarkers include acetoacetic acid and β-hydroxybutyric acid...
Ketones are well-known biomarkers of fat oxidation produced in the liver as a result of lipolysis. These biomarkers include acetoacetic acid and β-hydroxybutyric acid in the blood/urine and acetone in our breath and skin. Monitoring ketone production in the body is essential for people who use caloric intake deficit to reduce body weight or use ketogenic diets for wellness or therapeutic treatments. Current methods to monitor ketones include urine dipsticks, capillary blood monitors, and breath analyzers. However, these existing methods have certain disadvantages that preclude them from being used more widely. In this work, we introduce a novel acetone sensor device that can detect acetone levels in breath and overcome the drawbacks of existing sensing approaches. The critical element of the device is a robust sensor with the capability to measure acetone using a complementary metal oxide semiconductor (CMOS) chip and convenient data analysis from a red, green, and blue deconvolution imaging approach. The acetone sensor device demonstrated sensitivity of detection in the micromolar-concentration range, selectivity for detection of acetone in breath, and a lifetime stability of at least one month. The sensor device utility was probed with real tests on breath samples using an established blood ketone reference method.
Topics: Humans; Acetone; Body Fluids; Ketones; 3-Hydroxybutyric Acid; Biomarkers
PubMed: 38248381
DOI: 10.3390/bios14010004 -
Critical Care Explorations Jan 2024We sought to assess whether genetic associations with metabolite concentrations in septic shock patients could be used to identify pathways of potential importance for...
OBJECTIVES
We sought to assess whether genetic associations with metabolite concentrations in septic shock patients could be used to identify pathways of potential importance for understanding sepsis pathophysiology.
DESIGN
Retrospective multicenter cohort studies of septic shock patients.
SETTING
All participants who were admitted to 27 participating hospital sites in three countries (Australia, New Zealand, and the United Kingdom) were eligible for inclusion.
PATIENTS
Adult, critically ill, mechanically ventilated patients with septic shock ( = 230) who were a subset of the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock trial (ClinicalTrials.gov number: NCT01448109).
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
A genome-wide association study was conducted for a range of serum metabolite levels for participants. Genome-wide significant associations ( ≤ 5 × 10) were found for the two major ketone bodies (3-hydroxybutyrate [rs2456680] and acetoacetate [rs2213037] and creatinine (rs6851961). One of these single-nucleotide polymorphisms (SNPs) (rs2213037) was located in the alcohol dehydrogenase cluster of genes, which code for enzymes related to the metabolism of acetoacetate and, therefore, presents a plausible association for this metabolite. None of the three SNPs showed strong associations with risk of sepsis, 28- or 90-day mortality, or Acute Physiology and Chronic Health Evaluation score (a measure of sepsis severity).
CONCLUSIONS
We suggest that the genetic associations with metabolites may reflect a starvation response rather than processes involved in sepsis pathophysiology. However, our results require further investigation and replication in both healthy and diseased cohorts including those of different ancestry.
PubMed: 38239409
DOI: 10.1097/CCE.0000000000001030 -
Journal of Diabetes Research 2024This study is aimed at examining which factors are useful for the diagnosis and distinction of ketoacidosis. We recruited 21 diabetic ketoacidosis (DKA) and alcoholic...
This study is aimed at examining which factors are useful for the diagnosis and distinction of ketoacidosis. We recruited 21 diabetic ketoacidosis (DKA) and alcoholic ketoacidosis (AKA) patients hospitalized in Kawasaki Medical School General Medical Center from April 2015 to March 2021. Almost all patients in this study were brought to the emergency room in a coma and hospitalized. All patients underwent blood gas aspiration and laboratory tests. We evaluated the difference in diagnosis markers in emergencies between DKA and alcoholic ketoacidosis AKA. Compared to AKA patients, DKA patients had statistically higher values of serum acetoacetic acid and lower values of serum lactate, arterial blood pH, and base excess. In contrast, total ketone bodies, -hydroxybutyric acid, and -hydroxybutyric acid/acetoacetic acid ratio in serum did not differ between the two patient groups. It was shown that evaluation of each pathology such as low body weight, diabetes, liver dysfunction, and dehydration was important. It is important to perform differential diagnosis for taking medical histories such as insulin deficiency, alcohol abuse, or starvation as the etiology in Japanese subjects with DKA or AKA. Moreover, it is important to precisely comprehend the pathology of dehydration and alcoholic metabolism which would lead to appropriate treatment for DKA and AKA.
Topics: Humans; Diabetic Ketoacidosis; Retrospective Studies; 3-Hydroxybutyric Acid; Dehydration; Ketosis; Diabetes Mellitus; Acetoacetates
PubMed: 38225984
DOI: 10.1155/2024/8889415 -
International Journal of Molecular... Dec 2023Ketone bodies (KBs), such as acetoacetate and β-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. KBs, generated through... (Review)
Review
Ketone bodies (KBs), such as acetoacetate and β-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA in extrahepatic tissues, entering the tricarboxylic acid cycle and electron transport chain for ATP production. Reduced glucose metabolism and mitochondrial dysfunction correlate with increased neuronal death and brain damage during cerebral ischemia and neurodegeneration. Both KBs and the ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes through metabolic and signaling functions. They enhance mitochondrial function, mitigate oxidative stress and apoptosis, and regulate epigenetic and post-translational modifications of histones and non-histone proteins. Additionally, KBs and KD contribute to reducing neuroinflammation and modulating autophagy, neurotransmission systems, and gut microbiome. This review aims to explore the current understanding of the molecular mechanisms underpinning the neuroprotective effects of KBs and KD against brain damage in cerebral ischemia and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease.
Topics: Humans; Ketone Bodies; Neurodegenerative Diseases; Neuroprotection; Neuroprotective Agents; Diet, Ketogenic; Cerebral Infarction; Brain Injuries
PubMed: 38203294
DOI: 10.3390/ijms25010124 -
Communications Biology Jan 2024Torpor and arousal cycles, both daily and seasonal (e.g. hibernation), are crucial for small mammals, including bats, to maintain the energy and water balance. The...
Torpor and arousal cycles, both daily and seasonal (e.g. hibernation), are crucial for small mammals, including bats, to maintain the energy and water balance. The alternation between torpor and arousal leads to metabolic changes, leaving traceable evidence of metabolic wastes in urine. In this study we investigated urinary creatinine and acetoacetate (a ketone body) in the Eastern bent-wing bat (Miniopterus fuliginosus) in Mungyeong, South Korea. We found an increase in urinary creatinine during torpor in summer, indicating changes in renal water reabsorption rates during the active season. Although we could not confirm ketonuria in hibernating bats due to a methodological limitation caused by the small amount of urine, we verified an increase in urinary creatinine concentration during hibernation. This finding suggests that managing water stress resulting from evaporative water loss is one of key reasons for arousal during hibernation in Eastern bent-wing bats.
Topics: Animals; Hibernation; Chiroptera; Creatinine; Torpor; Republic of Korea
PubMed: 38182741
DOI: 10.1038/s42003-023-05713-1 -
Bioengineering (Basel, Switzerland) Nov 2023The depletion of fossil fuel resources and the CO emissions coupled with petroleum-based industrial processes present a relevant issue for the whole of society. An...
The depletion of fossil fuel resources and the CO emissions coupled with petroleum-based industrial processes present a relevant issue for the whole of society. An alternative to the fossil-based production of chemicals is microbial fermentation using acetogens. Acetogenic bacteria are able to metabolize CO or CO (+H) via the Wood-Ljungdahl pathway. As isopropanol is widely used in a variety of industrial branches, it is advantageous to find a fossil-independent production process. In this study, was employed to produce isopropanol via plasmid-based expression of the enzymes thiolase A, CoA-transferase, acetoacetate decarboxylase and secondary alcohol dehydrogenase. An examination of the enzymes originating from different organisms led to a maximum isopropanol production of 5.64 ± 1.08 mM using CO + H as the carbon and energy source. To this end, the genes (encoding thiolase A) and (encoding CoA-transferase) of , (encoding acetoacetate decarboxylase) originating from and (encoding secondary alcohol dehydrogenase) of DSM 6423 were employed. Since bottlenecks in the isopropanol production pathway are known, optimization of the strain was investigated, resulting in a 2.5-fold increase in isopropanol concentration.
PubMed: 38135972
DOI: 10.3390/bioengineering10121381 -
Metabolites Nov 2023H-NMR metabolomics data is increasingly used to track health and disease. Nightingale Health, a major supplier of H-NMR metabolomics, has recently updated the...
H-NMR metabolomics data is increasingly used to track health and disease. Nightingale Health, a major supplier of H-NMR metabolomics, has recently updated the quantification strategy to further align with clinical standards. Such updates, however, might influence backward replicability, particularly affecting studies with repeated measures. Using data from BBMRI-NL consortium (~28,000 samples from 28 cohorts), we compared Nightingale data, originally released in 2014 and 2016, with a re-quantified version released in 2020, of which both versions were based on the same NMR spectra. Apart from two discontinued and twenty-three new analytes, we generally observe a high concordance between quantification versions with 73 out of 222 (33%) analytes showing a mean ρ > 0.9 across all cohorts. Conversely, five analytes consistently showed lower Spearman's correlations (ρ < 0.7) between versions, namely acetoacetate, LDL-L, saturated fatty acids, S-HDL-C, and sphingomyelins. Furthermore, previously trained multi-analyte scores, such as or , might be particularly sensitive to platform changes. Whereas replicated well, the score had to be retrained due to use of discontinued analytes. Notably, both scores in the re-quantified data recapitulated mortality associations observed previously. Concluding, we urge caution in utilizing different platform versions to avoid mixing analytes, having different units, or simply being discontinued.
PubMed: 38132863
DOI: 10.3390/metabo13121181 -
MBio Feb 2024Acetone carboxylases (ACs) catalyze the metal- and ATP-dependent conversion of acetone and bicarbonate to form acetoacetate. Interestingly, two homologous ACs that have...
Acetone carboxylases (ACs) catalyze the metal- and ATP-dependent conversion of acetone and bicarbonate to form acetoacetate. Interestingly, two homologous ACs that have been biochemically characterized have been reported to have different metal complements, implicating different metal dependencies in catalysis. ACs from proteobacteria and share 68% sequence identity but have been proposed to have different catalytic metals. In this work, the two ACs were expressed under the same conditions in and were subjected to parallel chelation and reconstitution experiments with Mn(II) or Fe(II). Electron paramagnetic and Mössbauer spectroscopies identified signatures, respectively, of Mn(II) or Fe(II) bound at the active site. These experiments showed that the respective ACs, without the assistance of chaperones, second metal sites, or post-translational modifications facilitate correct metal incorporation, and despite the expected thermodynamic preference for Fe(II), each preferred a distinct metal. Catalysis was likewise associated uniquely with the cognate metal, though either could potentially serve the proposed Lewis acidic role. Subtle differences in the protein structure are implicated in serving as a selectivity filter for Mn(II) or Fe(II).IMPORTANCEThe Irving-Williams series refers to the predicted stabilities of transition metal complexes where the observed general stability for divalent first-row transition metal complexes increase across the row. Acetone carboxylases (ACs) use a coordinated divalent metal at their active site in the catalytic conversion of bicarbonate and acetone to form acetoacetate. Highly homologous ACs discriminate among different divalent metals at their active sites such that variations of the enzyme prefer Mn(II) over Fe(II), defying Irving-Williams-predicted behavior. Defining the determinants that promote metal discrimination within the first-row transition metals is of broad fundamental importance in understanding metal-mediated catalysis and metal catalyst design.
Topics: Acetone; Acetoacetates; Manganese; Bicarbonates; Coordination Complexes; Metals; Ferrous Compounds; Catalysis
PubMed: 38126751
DOI: 10.1128/mbio.02987-23