Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Plasma vitamin levels and pathway analysis in boys with autism spectrum disorders

Thu, 05/12/2024 - 12:00
Sci Rep. 2024 Dec 5;14(1):30344. doi: 10.1038/s41598-024-82260-7.ABSTRACTAbnormal feeding behaviors and inadequate nutrient intake of children with autism spectrum disorder (ASD) have been reported. This study aimed to examine the plasma vitamin status of boys with autism spectrum disorder (ASD) and to analyze the association between vitamin status and symptoms of ASD. A total of 45 boys with ASD (age = 3.25 ± 0.68 years) and 45 typically developing (TD) boys (age = 3.33 ± 0.66 years) were enrolled. The developmental levels were evaluated using the Gesell Developmental Schedules (GDS), the severity of ASD was evaluated using the Childhood Autism Rating Scale (CARS). The plasma vitamin levels were determined using metabolomics method. The Vitamin B1, nicotinamide, pyridoxamine dihydrochloride and Vitamin E were found to be significantly higher in the boys with ASD compared with those without ASD. In addition, no significant differences in vitamin metabolic pathways were found between the ASD group and the TD group.The nicotinamide and pyridoxamine dihydrochloride concentration were found to be negatively correlated with GDS score. In comparison with TD boys, the plasma vitamin concentration of ASD boys was not insufficient. Further studies are required to investigate whether it is necessary to use vitamin nutritional supplements in children with ASD.PMID:39639123 | DOI:10.1038/s41598-024-82260-7

Multi-omics analysis and longitudinal study of reprogramming by dietary creatine to endogenous metabolism in largemouth bass (Micropterus salmoides)

Thu, 05/12/2024 - 12:00
Fish Physiol Biochem. 2025 Feb;51(1):1-18. doi: 10.1007/s10695-024-01417-3. Epub 2024 Dec 6.ABSTRACTCreatine is a feed additive with physiological pleiotropic properties and also an energy homeostasis protector in vertebrates and is successfully used in terrestrial livestock and aquaculture. Here, two feeding trials were performed to investigate dietary creatine on endogenous creatine metabolism and physiological reprogramming in largemouth bass. The results showed that the endogenous creatine metabolism genes AGAT, GAMT, and SLC6A8 of largemouth bass are highly conserved with the amino acid sequences of other teleosts and are clustered separately from mammals. Among the 16 major tissues in largemouth bass, both creatine synthesis genes (agat, gamt) and transporter gene slc6a8 are most highly expressed in muscle. Muscle has a high threshold but sensitive creatine negative feedback to regulate endogenous creatine metabolism. Dietary creatine intake significantly inhibits endogenous creatine synthesis and transport in muscle in a dose-dependent manner, and this inhibitory effect recovers with a decrease in dietary creatine content. In addition, physiological creatine saturation required prolonged exogenous creatine intake, and it would be shortened by high doses of creatine, which provides guidance for maximizing economic benefits in aquaculture. Metabolome and transcriptome showed that dietary creatine significantly affected the metabolism of the creatine precursor substance-arginine. Exogenous creatine intake spared arginine that would otherwise be used for creatine synthesis, increased arginine levels, and caused reprogramming of arginine metabolism. Overall, these results demonstrate that the addition of creatine to largemouth bass diets is safe and recoverable, and the benefits of creatine intake in largemouth bass are not limited to enhancing the function of creatine itself but also include a reduction in the metabolic burden of essential amino acids to better growth performance.PMID:39638990 | DOI:10.1007/s10695-024-01417-3

Triaptosis: an endosome-dependent cell death modality

Thu, 05/12/2024 - 12:00
Cell Res. 2024 Dec 6. doi: 10.1038/s41422-024-01053-9. Online ahead of print.NO ABSTRACTPMID:39638924 | DOI:10.1038/s41422-024-01053-9

Effects of surfactin stress on gene expression and pathological changes in Spodoptera litura

Thu, 05/12/2024 - 12:00
Sci Rep. 2024 Dec 5;14(1):30357. doi: 10.1038/s41598-024-81946-2.ABSTRACTSpodoptera litura (S. litura) is a polyphagous pest of the family Lepidoptera, which causes damage and yields losses to many crops. The long-term use of chemical pesticides for control not only seriously threatens environmental health, but also causes S. litura to develop drug resistance. Therefore, there is an urgent need to develop environmentally safe and friendly biogenic pesticides. However, the mechanism of action of the secondary metabolite (surfactin) of Bacillus Vélezensis (B. vélezensis) on lepidopteran pests (S. litura) has not been reported yet. We found that several metabolites and genes in S. litura were affected by surfactin exposure. The expressions of the metabolites (protoporphyrinogen (PPO), gluconolactone (GDL), and L-cysteate) were significantly down-regulated while glutamate and hydroxychloroquine were significantly up-regulated. The expression levels of genes related to drug metabolism and detoxification, include the glutathione s-transferase (GST) gene family and acetaldehyde dehydrogenase (ALDH), and apoptosis-inhibiting genes (seven in absentia homolog 1(SIAH1)) were significantly decreased. In addition, pathological changes occurred in intestinal wall cells, Malpighian tubule cells, and nerve cells of S. litura under surfactin stress. Conclusively, our results suggest that surfactin induces an increase in reactive oxygen species (ROS) and damages S. litura cells. Furthermore, based on the integrated analysis of transcriptomic and metabolomic data, it is hypothesized that surfactin may also trigger neurotoxicity and cardiotoxicity in S. litura while hindering the insect's detoxification processes. This study lays a foundation for further exploration of surfactin as a potential biopesticide.PMID:39638883 | DOI:10.1038/s41598-024-81946-2

A multi-omics approach identifies the key role of disorders of sphingolipid metabolism in Ang II-induced hypertensive cardiomyopathy myocardial remodeling

Thu, 05/12/2024 - 12:00
Sci Rep. 2024 Dec 5;14(1):30379. doi: 10.1038/s41598-024-81611-8.ABSTRACTHypertension-induced myocardial remodelling encompasses both structural and functional changes in cardiac muscle tissue, such as myocardial hypertrophy, fibrosis, and inflammation. These alterations not only impair the systolic and diastolic functions of the heart but also elevate the risk of cardiovascular events and heart failure. One of the primary contributors to hypertensive cardiomyopathy (HTN-CM) is the over-activation of the renin-angiotensin-aldosterone system (RAAS), which subsequently induces myocardial remodeling. Although conventional therapeutic strategies aim to suppress RAAS and slow the progression of heart failure, the primary challenge in treating HTN-CM remains the lack of sensitive and specific biomarkers for early detection of myocardial remodelling. Combined multi-omics analyses, complemented by experimental validation, offer a systematic understanding of the landscape of gene/protein/metabolite expression in HTN-CM, revealing the underlying mechanisms of angiotensin II (Ang II)-induced myocardial remodeling in HTN-CM. Transcriptomic analysis revealed that differentially expressed genes (DEGs) are implicated in sphingolipid metabolic processes and are associated with collagen synthesis and inflammatory responses, collectively contributing to myocardial remodeling in HTN-CM. Proteomic analysis demonstrated that differentially expressed proteins (DEPs) are also involved in inflammatory and fibrotic processes, with associations to sphingolipid signaling pathways, particularly manifested through elevated expression of IL6, COL4A1, FGG, FGB, CREBBP and SPHK2 proteins. Metabolomic profiling further elucidated the increased expression of bioactive sphingolipid metabolites S1P and Sa1P in the myocardium of HTN-CM. Integrative multi-omics analysis revealed that HTN-CM is primarily influenced by the sphingolipid signaling pathway, with additional associations to the HIF-1α and FoxO signaling pathways. Correlation analysis has highlighted strong associations between sphingolipids and genes/proteins related to fibrosis and inflammation, as well as their connection to the HIF-1α and FoxO signalling pathways. Furthermore, certain key indicators were validated through ELISA and Western blot analyses in both plasma and myocardial tissue. In conclusion, the findings of this study suggest that excessive Ang II may induce abnormalities in sphingolipid metabolism, resulting in increased levels of S1P in both circulating and myocardial tissues. This elevation in S1P is implicated in myocardial inflammatory and fibrotic alterations, highlighting its pivotal role in myocardial remodeling. The specific mechanism underlying the sphingolipid signaling pathway in myocardial remodeling may involve downstream biological processes, including oxidative stress and excessive mitochondrial autophagy, mediated by HIF-1α and FoxO.PMID:39638825 | DOI:10.1038/s41598-024-81611-8

Metabolomic Profiling, in-vitro and in-silico study of anti-HSV activity of standardized Eucalyptus maculata (Corymbia maculata) Resin Extract

Thu, 05/12/2024 - 12:00
Chem Biodivers. 2024 Dec 5:e202401484. doi: 10.1002/cbdv.202401484. Online ahead of print.ABSTRACTRecent episodes of viral pandemics have led to a quest for new drugs to act on emerging targets. Most challenging viruses are only mutants of already known viruses. Here comes the role of metabolomics in investigating natural secondary metabolites as sustainable antiviral drug candidates. Resins are natural plant products having the advantage of being concentrated and consisting of precious terpenoids, phenolics and flavonoids, known for their anti-pathogen activity. This study aimed at investigation of the major phytoconstituents in the Eucalyptus maculata (EM) resin using high resolution LC-MS/MS and investigating its antiviral potential. In vitro screening of the standardized EM antiviral activity was performed. High resolution LC-MS/MS analysis was done for the extract followed by investigation of the possible active metabolites through molecular docking techniques against two viral protein targets; herpes simplex virus glycoprotein D (HSV gD) and BTLA/HVEM complex. The evaluation in negative and positive modes identified 29 substances and revealed the prevalence of coumaryl and galloyl derivatives, in addition to kaempferol and aromadendrin derivatives. Antiviral in-vitro screening led to the conclusion of the promising effect of the resin against HSV which was further confirmed through molecular docking. EM resin represents a future sustainable drug discovery.PMID:39638765 | DOI:10.1002/cbdv.202401484

Ninety-Day Subchronic Toxicology of Individual and Combined Toxicants from the Thermal Processing of Lipid-Rich Foods

Thu, 05/12/2024 - 12:00
J Agric Food Chem. 2024 Dec 5. doi: 10.1021/acs.jafc.4c07892. Online ahead of print.ABSTRACTOxidative derivatives of triacylglycerols (ox-TGs), aldehydes, and 3-monochloropropane-1,2-diol esters (3-MCPDE) were simultaneously evaluated in a 90-day subchronic study, focusing on biological indicators, biochemical indicators, and serum metabolomics as the first part of integrated toxicity and interactions. After 90 days of feeding Kunming mice, coexposure to combined toxicants significantly inhibited the trend of liver weight gain, reduced the levels of total bilirubin (TBIL) and direct bilirubin (DBIL), and decreased uric acid (UA) compared to individual toxicant exposure. A total of 21 and 31 biomarkers in female and male mice were identified, respectively. Co-exposure to combined toxicants might mitigate the changes in cytidine, CDP, dUMP, and dUDP involved in purine and pyrimidine metabolism caused by a single exposure, but exacerbate the changes in l-tryptophan, 5-hydroxy-l-tryptophan, and 5-hydroxyindoleacetic acid, which are involved in tryptophan metabolism. These results provided new insights into a comprehensive toxicity and interaction evaluation model of multiple combined toxicants in food.PMID:39638751 | DOI:10.1021/acs.jafc.4c07892

Metabolic Profiles of Critical Care Patients to Confirm Sepsis and Further Understand the Metabolic Phenotype of Sepsis

Thu, 05/12/2024 - 12:00
Crit Care Nurs Q. 2025 Jan-Mar 01;48(1):8-14. doi: 10.1097/CNQ.0000000000000540. Epub 2024 Dec 2.ABSTRACTSepsis remains a major concern in health care globally. Despite decades of research, incidence is on the rise, and mortality remains high. Costs are staggering. Additionally, the outdated sepsis bundle established based on SIRS, remains the standard by which providers are held accountable. It is now accepted that organ dysfunction in sepsis is secondary to cellular metabolic dysregulation. Technology for metabolic monitoring should be explored for improved, early recognition of sepsis. We sought to investigate the underlying metabolic profile of patients with sepsis, to determine the value of continuous metabolic monitoring technology. The investigators partnered with industry, to trial noninvasive monitoring of the cellular metabolite carbon dioxide, under a prospective, observational design. During the 6-month trial, the investigators collected data from the electronic medical record of patients using the technology, to determine the specific metabolic differences between patients with and without sepsis. The investigators found serum carbon dioxide (paCO2) was significantly lower in patients with sepsis, and, low paCO2 had a significant inverse relationship to serum lactate. This finding supports the notion that paCO2 is low in sepsis secondary to metabolic dysregulation and not hyperventilation, which had historically explained low paCO2 under the SIRS model. Metabolic monitoring is available, easy to apply and manage, and contributes valuable information in the detection of sepsis. Further research should be done to understand trends in serum CO2 and its relationship to the development of sepsis. This study also provides important further support for the emerging understanding of the dysregulated host response in sepsis.PMID:39638331 | DOI:10.1097/CNQ.0000000000000540

Cadmium alters the cellular metabolome of human ovarian granulosa cells

Thu, 05/12/2024 - 12:00
Toxicol Appl Pharmacol. 2024 Dec 3:117187. doi: 10.1016/j.taap.2024.117187. Online ahead of print.ABSTRACTCadmium (Cd) is a toxic heavy metal that has been extensively implicated in disordered folliculogenesis, but the mechanisms underlying the ovarian toxicity of Cd remain to be explored fully. Granulosa cells are key players in ovarian follicular development and are the primary cells affected by Cd exposure-induced damage and dysfunction. In this study, we investigated how various levels of exposure of Cd (3 and 10 μM) to human granulosa cells (KGN cells) impacted the metabolism of the KGN cells utilizing a non-targeted metabolomics methodology. In vitro cell experiments revealed that Cd exposure dose-dependently diminished the viability of KGN cells. Metabolomics analysis revealed the presence of 296 (182 elevated and 114 reduced) and 397 (244 elevated and 153 reduced) differentially expressed metabolites after exposure to 3 and 10 μM, respectively. Cd exposure was found to significantly enrich nucleotide metabolism, sphingolipid metabolism, and ABC transporters in both groups. Although amino acid metabolic pathways exhibited significant enrichment across all groups, only glutathione, cysteine, and methionine metabolism were notably enriched in KGN cells exposed to 3 μM Cd, while glutathione and tryptophan metabolism were significantly enriched in the 10 μM Cd exposure cohort. The outcomes of this study provide mechanistic clues for elucidating Cd's cytotoxic impact on granulosa cells, and deepen our understanding of the ovarian toxicity of Cd.PMID:39638002 | DOI:10.1016/j.taap.2024.117187

Lipidomic and metabolomic changes in dysglycemia and the relationship to subclinical atherosclerosis: Not missing the forest for the trees

Thu, 05/12/2024 - 12:00
Int J Cardiol. 2024 Dec 3:132881. doi: 10.1016/j.ijcard.2024.132881. Online ahead of print.NO ABSTRACTPMID:39637995 | DOI:10.1016/j.ijcard.2024.132881

Taurine Synthesis by 2-Aminoethanethiol Dioxygenase as a Vulnerable Metabolic Alteration in Pancreatic Cancer

Thu, 05/12/2024 - 12:00
Biomol Ther (Seoul). 2024 Dec 5. doi: 10.4062/biomolther.2024.086. Online ahead of print.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) exhibits an altered metabolic profile compared to normal pancreatic tissue. However, studies on actual pancreatic tissues are limited. Untargeted metabolomics analysis was conducted on 54 pairs of tumor and matched normal tissues. Taurine levels were validated via immunohistochemistry (IHC) on separate PDAC and normal tissues. Bioinformatics analysis of transcriptomics and proteomics data evaluated genes associated with taurine metabolism. Identified taurine-associated gene was validated through gene modulation. Clinical implications were evaluated using patient data. Metabolomics analysis showed a 2.51-fold increase in taurine in PDAC compared to normal tissues (n=54). IHC confirmed this in independent samples (n=99 PDAC, 19 normal). Bioinformatics identified 2-aminoethanethiol dioxygenase (ADO) as a key gene modulating taurine metabolism. IHC on a tissue microarray (39 PDAC, 10 normal) confirmed elevated ADO in PDAC. The ADOTaurine axis correlated with PDAC recurrence and disease-free survival. ADO knockdown reduced cancer cell proliferation and tumor growth in a mouse xenograft model. The MEK-related signaling pathway is suggested to be modulated by ADO-Taurine metabolism. Our multi-omics investigation revealed elevated taurine synthesis mediated by ADO upregulation in PDAC. The ADOTaurine axis may serve as a biomarker for PDAC prognosis and a therapeutic target.PMID:39637922 | DOI:10.4062/biomolther.2024.086

How heatwaves impact microalgae in the presence of environmentally relevant PFAS concentration: Metabolic shifts and challenges posed

Thu, 05/12/2024 - 12:00
J Hazard Mater. 2024 Nov 27;484:136640. doi: 10.1016/j.jhazmat.2024.136640. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS) are widely distributed in the aquatic environment. While increasing studies have investigated the effects of specific PFAS exposure on microalgae, the impact of environmentally relevant PFAS concentrations, particularly during extreme weather events like heatwaves, remains unclear. For Microcystis aeruginosa, a cyanobacteria causing harmful algal blooms, PFAS exposure promoted growth and photosynthesis by accelerating the TCA cycle, intensifying carbon/nitrogen and nucleotide metabolism, and enhancing antioxidant expression. Moreover, although heatwave exposure alone adversely affected algal growth, co-exposure to PFAS and heatwaves paradoxically enhanced algal growth. This co-exposure also enhanced the expression of photosynthetic pigments and metabolites involved in alanine, aspartate and glutamate metabolism, as well as arginine and proline metabolism (compared to PFAS exposure alone). Nevertheless, co-exposure intensified oxidative stress, leading to differential expression of antioxidants, which may consequently affect the synthesis of membrane lipids. In addition, PFAS adsorption and uptake are primarily influenced by the varying strengths of PFAS molecules in binding with proteins and notably boosted by heatwaves. This study highlights the role of diverse PFAS in microalgae blooms and the influence of heatwave events on pollutant responses, providing scientific foundations for aquatic ecosystem protection against climate and pollution challenges.PMID:39637790 | DOI:10.1016/j.jhazmat.2024.136640

Ameliorative role of Tetrapleura tetraptera (Schum. & Thonn.) taub in cadmium chloride-induced oxidative stress in Drosophila melanogaster using in vivo and computational approaches

Thu, 05/12/2024 - 12:00
J Trace Elem Med Biol. 2024 Nov 28;87:127571. doi: 10.1016/j.jtemb.2024.127571. Online ahead of print.ABSTRACTBACKGROUND: Cadmium (Cd) is a naturally occurring transition metal associated with oxidative stress in living organisms. Whereas Tetrapleura tetraptera (Tt), an ethnomedicinal plant is said to possess high antioxidant activity and used to treat various human diseases locally. Therefore, the study aimed to investigate the biological activity of the ethanolic pod extract of T. tetraptera in cadmium chloride-induced toxicity in Drosophila melanogaster.METHODS: Six groups of adults (1-3 days old) D. melanogaster as shown: Control, Tt 2.5 mg/10 g diet, Tt 5 mg/10 g diet, CdCl2, CdCl2+ Tt 2.5 mg/10 diet and CdCl2+Tt 5 mg/10 g diet were exposed via diet for 7 days consisting of 50 flies per vial and 5 replicate per group. Thereafter, we evaluated markers for free radical generation, antioxidant, non-antioxidant activities, and emergence rates of the flies. The active compounds of Tt extract were molecularly docked against glutathione-S-transferase II.RESULTS: The results indicated that CdCl2 significantly induced oxidative stress by increasing the levels of lipid peroxidation (LPO), hydrogen peroxide (H2O2), nitric oxide (NO) and decreasing the activity of GST without an effect on total thiol (T-SH) and non-protein thiols (NP-SHs) levels. However, co-treatment with T. tetraptera (2.5 mg/10 g diet) significantly decreased levels of LPO, H2O2, but increased GST activity. Also, co-treatment with T. tetraptera (5 mg/10 g diet) increased NPSH and T-SH levels by 18.6 % and 35.8 %. Furthermore, Co-treatment (5 mg/10 g diet) increased the rate of offspring emergence.CONCLUSION: T. tetraptera ameliorated cadmium chloride-induced oxidative stress in Drosophila melanogaster and increased offspring hatching rate. T. tetraptera may therefore serve as a good regimen for the treatment of oxidative stress-related diseases induced by cadmium.PMID:39637735 | DOI:10.1016/j.jtemb.2024.127571

Combining non-targeted and targeted metabolomics to study key bitter and astringent substances of Liupao tea

Thu, 05/12/2024 - 12:00
Food Chem. 2024 Nov 29;467:142289. doi: 10.1016/j.foodchem.2024.142289. Online ahead of print.ABSTRACTLiupao tea is a post-fermented dark tea with bitterness and astringency as key sensory traits, though its chemical composition is not fully understood. Six Liupao tea samples with significant differences in bitterness and astringency were analyzed using non-targeted metabolomics and sensory evaluation. Thirty finished and five semi-finished Liupao tea samples were analyzed using UHPLC-MS-PRM for targeted quantification of bitter and astringent compounds. The results show that 477 non-volatile compounds were detected, including 18 potential bitter compounds and 22 potential astringent compounds. Six key bitter compounds (epigallocatechin gallate, catechin gallate, caffeine, quinic acid, neochlorogenic acid, and caffeic acid) and 11 key astringent compounds (e.g., epigallocatechin gallate, gallic acid, chlorogenic acid, ellagic acid) were identified. After fermentation, flavonoid glycosides and flavanols were reduced by 62.41 % to 97.46 %, while phenolic acids showed varied trends. Different rates of change in key compounds during fermentation resulted in variations in bitterness and astringency. This study offers insights for improving Liupao tea quality.PMID:39637669 | DOI:10.1016/j.foodchem.2024.142289

The role of structure in the interaction between bacteria, mammary epithelial cells and milk fat globules from raw or "cultured" milk

Thu, 05/12/2024 - 12:00
Food Chem. 2024 Nov 26;467:142244. doi: 10.1016/j.foodchem.2024.142244. Online ahead of print.ABSTRACTThe study aimed to distinguish between the role played by the structural properties of MFG from its chemical composition in modulating its interaction with pathogenic and commensal bacteria. MFG from mammary gland epithelial cells (MEC) or raw milk was tested. Small MFG from both sources promoted growth of B.subtilis while large MFG triggered biofilm formation. Metabolomic profiles supported these findings for MEC-derived MFG. In contrast, pathogenic bacteria like E. coli weren't affected by MFG size from both sources. Using lipid mixture formulated to mimic the chemical composition of small MFG did not induce growth of the bacteria. Results validate that (i) milk components secreted by MEC share some structural-functional properties with raw MFG and (ii) the structure of the MFG plays a pivotal role in modulating the interaction between milk fat and bacteria. Taken together, MFG size variations may provide a competitive advantage to commensal bacteria as a protective mechanism.PMID:39637660 | DOI:10.1016/j.foodchem.2024.142244

Maternal bisphenol A (BPA) exposure induces placental dysfunction and health risk in adult female offspring: Insights from a mouse model

Thu, 05/12/2024 - 12:00
Sci Total Environ. 2024 Dec 4;958:177714. doi: 10.1016/j.scitotenv.2024.177714. Online ahead of print.ABSTRACTBisphenol A (BPA) is an endocrine disruptor that poses multiple risks to human health. In particular, the potential adverse effects of maternal exposure to BPA on offspring warrant further investigation. In this study, pregnant mice were exposed to BPA throughout gestation and the effects of BPA on placental function, fetal development, and health risks in adult offspring were assessed. The results showed that exposure to BPA during pregnancy led to abnormal fetal weight during the mid-to-late stages. Positron emission tomography (PET)/computed tomography (CT) and quantitative polymerase chain reaction (qPCR) were used to assess the expression of glucose transporters. The results showed that maternal BPA exposure altered glucose transport by upregulating Glut1. This alteration may significantly affect placental function and fetal development. Placental metabolomic analysis showed that BPA exposure led to downregulation of key intermediates in glucose metabolism, including UDP-d-glucose and D-glucosamine-6-phosphate. Additionally, the glycerophospholipid metabolite Dipalmitoylphosphatidylcholine (DPPC) was upregulated while CDP-choline and CDP-ethanolamine were downregulated. These disturbances in placental energy metabolism and alterations in glucose transport may be related to decreased fasting blood glucose levels and abnormal glucose tolerance in female offspring; however, these indices remained unaltered in male offspring. These findings provide preliminary insights into the potential pathological mechanisms underlying placental dysfunction and health risk caused by maternal BPA exposure in adult female offspring.PMID:39637470 | DOI:10.1016/j.scitotenv.2024.177714

Shotgun Metabolomic Analysis of Killer Whale (Orcinus orca) Exhaled Breath Condensate

Thu, 05/12/2024 - 12:00
J Breath Res. 2024 Dec 5. doi: 10.1088/1752-7163/ad9ac5. Online ahead of print.ABSTRACTThe ocean is facing many anthropogenic stressors caused from both pollution and climate change. These stressors are significantly impacting and changing the ocean's ecosystem, and as such, methods must continually be developed that can improve our ability to monitor the health of marine life. For cetaceans, the current practice for health assessments of individuals requires live capture and release, which is expensive, usually stressful, and for larger species impractical. In this study, we investigated the potential of exhaled breath condensate (EBC) samples to provide unique metabolomic profiles from healthy killer whales (Orcinus orca) of varying known age and sex. EBC collection is a non-invasive procedure that has potential for remote collection using unmanned aerial vehicles, thus improving our ability to understand physiologic parameters within wild populations while minimizing stress from collection procedures However, descriptions of the available metabolome within EBC and its clinical significance within animals of known health and age must be described before this technique can be considered diagnostically useful. We describe normal variations of the metabolome across age and sex and provide evidence for the potential of this breath analysis method to become a valuable adjunctive tool for assessing the health of managed-care and free-ranging killer whales.PMID:39637438 | DOI:10.1088/1752-7163/ad9ac5

Left Ventricular Remodeling Predictors in Chronic Heart Failure of Ischemic Etiology

Thu, 05/12/2024 - 12:00
Kardiologiia. 2024 Nov 30;64(11):106-116. doi: 10.18087/cardio.2024.11.n2794.ABSTRACTAim To identify metabolomic and structure and function markers of remote left ventricular (LV) remodeling in patients with chronic heart failure (CHF) of ischemic etiology and LV ejection fraction (EF) <50%.Material and methods This prospective study included 56 patients with 3-4 NYHA functional class CHF of ischemic etiology (mean age, 66±7 years) and 50 patients with ischemic heart disease (IHD) without signs of CHF (69 [64; 73.7] years). Concentration of 19 amino acids, 11 products of kynurenine catabolism of tryptophan, 30 acylcarnitines with different chain lengths were measured in all participants. The metabolites that showed statistical differences between the comparison groups were then used for the analysis. Echocardiography was used to assess LV cavity remodeling at the time of the CHF patient inclusion in the study and after 6 months of follow-up. Predictors of long-term LV cavity remodeling were assessed for this cohort taking into account statistically significant echocardiographic parameters and metabolites.Results Patients with CHF of ischemic etiology, predominantly (81%) had pathological calculated types of LV remodeling (concentric and eccentric hypertrophy, 46 and 35%, respectively). However, this classification had limitations in describing this cohort. In addition, in this group, the concentrations of alanine, proline, asparagine, glycine, arginine, histidine, lysine, valine, indolyl-3-acetic acid, indolyl-3-propionic acid, C16-1-OH, and C16-OH were significantly (p<0.05) lower, and the concentrations of most medium- and long-chain acylcarnitines were higher than in patients with IHD without signs of CHF. The long-term (6 months) reverse remodeling of the LV cavity in CHF of ischemic etiology was influenced by changes in the interventricular septum thickness (hazard ratio, HR, 19.07; 95% confidence interval, CI, 1.76-206.8; p=0.006) and concentrations of anthranilic acid (HR 19.8; 95% CI 1.01-387.8; p=0.019) and asparagine (HR 8.76; 95% CI 1.07-71.4; p=0.031).Conclusion The presence of an interventricular septum thickness of more than 13.5 mm, anthranilic acid concentrations of higher than 0.235 μM/l, or an asparagine concentration of less than 135.2 μM/l in patients with CHF of ischemic etiology after 6 months of follow-up affects their achievement of LV cavity reverse remodeling.PMID:39637396 | DOI:10.18087/cardio.2024.11.n2794

Gut Microbiota and Related Metabolites in Children With Egg White Sensitization

Thu, 05/12/2024 - 12:00
Pediatr Infect Dis J. 2024 Dec 3. doi: 10.1097/INF.0000000000004628. Online ahead of print.ABSTRACTBACKGROUND: We hypothesized that food sensitization in children could be linked to specific gut microbiota. The objective of this study is to assess a group of children with egg white sensitization (ES) from the microbiological and biochemical-metabolic standpoint, applying the microbiota and metabolomics approach to studying the intestinal contents of the feces.METHODS: Twenty-eight toddlers with ES (mean age 13.08 months) and 24 healthy controls (mean age 12.85 months) were recruited for feces collection, serum IgE measurement, gut microbiota and metabolomics analysis. Individual microbial diversity and composition were analyzed via targeting the 16S rRNA gene hypervariable V3-V5 regions. The metabolite profiles of human feces were explored by 1H nuclear magnetic resonance.RESULTS: Children with ES exhibited relatively high levels of Firmicutes at the phylum level and relatively low levels of Bacteroidetes. Moreover, children with ES exhibited significantly reduced overall gut microbiota diversity and richness compared with healthy children. At the family level, we observed significant increases in the numbers of Clostridiaceae, Lachnospiraceae, Pasteurellaceae and Ruminococcaceae in children with ES. Egg white sensitivity increases orotic acid, nicotinate, methyl succinate, urocanic acid, xanthine, amino acids (tyrosine, lysine, tryptophan, phenylalanine) and short-chain fatty acids (n-butyrate, valerate) levels according to the results of metabolomics analysis.CONCLUSIONS: In summary, some specific families and genera (dysbiosis) are enriched in the gut microbiota, and increases in the mean concentrations of organic compounds in the fecal metabolite profile are associated with ES in children. These findings may provide evidence of potential strategies to control the development of ES or other atopies by modifying the gut microbiota.PMID:39637305 | DOI:10.1097/INF.0000000000004628

Metabolome and transcriptomics analyses reveal quality differences between Camellia tachangensis F. C. Zhang and C. sinensis (L.) O. Kunzte

Thu, 05/12/2024 - 12:00
PLoS One. 2024 Dec 5;19(12):e0314595. doi: 10.1371/journal.pone.0314595. eCollection 2024.ABSTRACTTea ranks among the top three most beloved non-alcoholic beverages worldwide and boasts significant economic and health benefits. In addition to Camellia sinensis (L.) O. Kuntze, and other Camellia plants in China are consumed by residents as tea drinks, which also have important economic value. The present study introduces one of the wild tea species, namely, Camellia tachangensis F. C. Zhang. We analyzed changes in metabolite abundance and gene expression patterns of C. tachangensis and C. sinensis using metabonomics and transcriptomics. We found 1056 metabolites, including 256 differential metabolites (67 upregulated and 189 downregulated). Additionally, transcriptome analysis revealed 8049 differentially expressed genes, with 4418 upregulated and 3631 downregulated genes. C. sinensis boasts a notable abundance of Amino acids, which can be attributed to its specific genetic makeup. In Theanine and Caffeine metabolic pathways, the levels of the majority of amino acids and caffeine tend to decrease. In Flavonoid biosynthesis, the levels of the Flavanone Fustin and Epicatechin are higher in C. tachangensis, while Epigallocatechin and Gallocatechin levels are higher in C. sinensis. This indicates that the metabolic components of C. sinensis and C. tachangensis are not identical, which may result in a unique flavor.PMID:39637125 | DOI:10.1371/journal.pone.0314595

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