PubMed

Anal Chem. 2025 Jan 13. doi: 10.1021/acs.analchem.4c06108. Online ahead of print.ABSTRACTFlow injection mass spectrometry (FI-MS) is widely employed for high-throughput metabolome analysis, yet the absence of prior separation leads to significant matrix effects, thereby limiting the metabolome coverage. In this study, we introduce a novel photosensitive MS probe, iTASO-ONH2, integrated with FI-MS to establish a high-throughput strategy for submetabolome analyses. The iTASO probe features a conjugated-imino sulfonate moiety for efficient photolysis under 365 nm irradiation and a reactive group for selective metabolite labeling. The iTASO-ONH2 probe effectively and selectively labels carbonyl compounds, forming highly stable labeled products. Upon UV exposure, the labeled products rapidly release sulfonic acid-containing photolysis products, detectable with high sensitivity in ESI-negative mode and low matrix effect, offering femtomole-level detection sensitivity. The iTASO-ONH2-based FI-MS strategy was applied to fecal samples from chronic sleep-deprived and control mice, revealing 192 potential carbonyl compounds of which 37 exhibited significant alterations. Additionally, three other photosensitive probes─iTASO-NH2, iTASO-NHS, and iTASO-MAL─were synthesized to selectively label carboxyl, amino, and thiol metabolites, respectively, underscoring the versatility of the iTASO-based FI-MS strategy for submetabolomic analysis across diverse metabolite classes.PMID:39804786 | DOI:10.1021/acs.analchem.4c06108

Minerva Gastroenterol (Torino). 2025 Jan 13. doi: 10.23736/S2724-5985.24.03781-1. Online ahead of print.ABSTRACTSmall intestinal bacterial overgrowth (SIBO) was originally described as a cause of maldigestion and malabsorption in situations where disruptions of intestinal anatomy or physiology favored the proliferation of bacteria normally confined to the colon. In this context, the pathogenesis of symptoms resulting from SIBO was well described. More recently, the concept of SIBO was extended to explain symptoms such as bloating, altered bowel habit and discomfort among individuals with irritable bowel syndrome and since then a whole host of gastrointestinal and extragastrointestinal disorders have been attributed to SIBO. In these more recent studies, the diagnosis of SIBO has been largely based on breath hydrogen testing; an approach that is subjected to misinterpretation. Here we critically assess the "modern" (as against the "classical") concept of SIBO and plead for caution in the application of breath tests, and those that employ lactulose as the substrate, in particular, to the diagnosis of this disorder. We look forward to the application of modern molecular microbiological techniques to the assessment of the small intestinal microbiome and metabolome and the delineation of what is truly normal.PMID:39804239 | DOI:10.23736/S2724-5985.24.03781-1

Cardiovasc Res. 2025 Jan 10:cvae267. doi: 10.1093/cvr/cvae267. Online ahead of print.ABSTRACTAIMS: The gastrointestinal (GI) tract is composed of distinct sub-regions, which exhibit segment-specific differences in microbial colonization and (patho)physiological characteristics. Gut microbes can be collectively considered as an active endocrine organ. Microbes produce metabolites, which can be taken up by the host and can actively communicate with the immune cells in the gut lamina propria with consequences for cardiovascular health. Variation in bacterial load and composition along the GI tract may influence the mucosal microenvironment and thus be reflected its interstitial fluid (IF). Characterization of the segment-specific microenvironment is challenging and largely unexplored because of lack of available tools.METHODS AND RESULTS: Here, we developed methods, namely tissue centrifugation and elution, to collect IF from the mucosa of different intestinal segments. These methods were first validated in rats and mice, and the tissue elution method was subsequently translated for use in humans. These new methods allowed us to quantify microbiota-derived metabolites, mucosa-derived cytokines, and proteins at their site-of-action. Quantification of short-chain fatty acids showed enrichment in the colonic IF. Metabolite and cytokine analyses revealed differential abundances within segments, often significantly increased compared to plasma, and proteomics revealed that proteins annotated to the extracellular phase were site-specifically identifiable in IF. Lipopolysaccharide injections in rats showed significantly higher ileal IL-1β levels in IF compared to the systemic circulation, suggesting the potential of local as well as systemic effect.CONCLUSION: Collection of IF from defined segments and the direct measurement of mediators at the site-of-action in rodents and humans bypasses the limitations of indirect analysis of faecal samples or serum, providing direct insight into this understudied compartment.PMID:39804196 | DOI:10.1093/cvr/cvae267

Epilepsia. 2025 Jan 13. doi: 10.1111/epi.18256. Online ahead of print.ABSTRACTOBJECTIVE: Idiopathic epilepsy (IE) is the most common chronic neurological disease in dogs and an established natural animal model for human epilepsy types with genetic and unknown etiology. However, the metabolic pathways underlying IE remain largely unknown.METHODS: Plasma samples of healthy dogs (n = 39) and dogs with IE (n = 49) were metabolically profiled (n = 121 known target metabolites) and fingerprinted (n = 1825 untargeted features) using liquid chromatography coupled to mass spectrometry. Dogs with IE were classified as mild phenotype (MP; n = 22) or drug-resistant (DR; n = 27). All dogs received the same standard adult maintenance diet for a minimum of 20 days (35 ± 11 days) before sampling. Data were analyzed using a combination of univariate (one-way analysis of variance or Kruskal-Wallis rank sum test), multivariate (limma, orthogonal partial least squares-discriminant analysis), and pathway enrichment statistical analysis.RESULTS: In dogs with both DR and MP IE, a distinct plasma metabolic profile and fingerprint compared to healthy dogs was observed. Metabolic pathways involved in these alterations included oxidative stress, inflammation, and amino acid metabolism. Moreover, significantly lower plasma concentrations of vitamin B6 were found in MP (p = .001) and DR (p = .005) compared to healthy dogs.SIGNIFICANCE: Our data provide new insights into the metabolic pathways underlying IE in dogs, further substantiating its potential as a natural animal model for humans with epilepsy, reflected by related metabolic changes in oxidative stress metabolites and vitamin B6. Even more, several metabolites within the uncovered pathways offer promising therapeutic targets for the management of IE, primarily for dogs, and ultimately for humans.PMID:39804158 | DOI:10.1111/epi.18256

Anal Chem. 2025 Jan 13. doi: 10.1021/acs.analchem.4c04692. Online ahead of print.ABSTRACTSimultaneous analysis of multiple phosphorylated metabolites (phosphorylated metabolome) in biological samples is vital to reveal their physiological and pathophysiological functions, which is extremely challenging due to their low abundance in some biological matrices, high hydrophilicity, and poor chromatographic behavior. Here, we developed a new method with ion-pair reversed-phase ultrahigh-performance liquid chromatography and mass spectrometry using BEH C18 columns modified with hybrid surface technology. This method demonstrated good performances for various phosphorylated metabolites, including phosphorylated sugars and amino acids, nucleotides, NAD-based cofactors, and acyl-CoAs in a single run using standard LC systems. Specifically, the method showed good retention (capacity factor > 2) and reproducibility (ΔtR < 0.09 min, n = 6), peak symmetry (tailing factor < 2), and sensitivity (limit-of-detection < 238 fmol-on-column with QTOFMS) for all tested analytes especially for the medium- and/or long-chain acyl-CoAs. The method demonstrated reproducible applicability across numerous biological matrices, including tissue (liver), human biofluids (urine, plasma), cells, and feces, and revealed significant molecular phenotypic differences in phosphorylated metabolite composition.PMID:39804109 | DOI:10.1021/acs.analchem.4c04692

Environ Sci Technol. 2025 Jan 13. doi: 10.1021/acs.est.4c05040. Online ahead of print.ABSTRACTThis study investigated the effects of fine-sized pork bone biochar particles on remediating As-contaminated soil and alleviating associated phytotoxicity to rice in 50-day short-term and 120-day full-life-cycle pot experiments. The addition of micro-nanostructured pork bone biochar (BC) pyrolyzed at 400 and 600 °C (BC400 and BC600) significantly increased the As-treated shoot and root fresh weight by 24.4-77.6%, while simultaneously reducing tissue As accumulation by 26.7-64.1% and increasing soil As content by 17.1-27.1% as compared to As treatment. Microbial community analysis demonstrated that BC600 and BC400 treatments increased the proportion of plant growth-promoting microbes such as Ceratobasidium and Achromobacter by 33-81.6% in the roots and As adsorption-associated Bacillus by 1.15-1.59-fold in the rhizosphere soil. Metabolomic profiling suggests that BC and As coexposure triggered differentially expressed metabolites (DEMs) enriched in lipid, carbohydrate, and amino acid metabolic pathways, all of which could alleviate As-induced phytotoxicity and promote plant As tolerance. Importantly, the quality of As-treated rice grains was improved by the BC amendments. This study demonstrates the significant potential of BC for enhancing crop growth and minimizing the As-induced phytotoxicity to rice and provides a framework for a promising strategy for remediating heavy metal(loid)-contaminated soil while simultaneously promoting food safety.PMID:39804013 | DOI:10.1021/acs.est.4c05040

bioRxiv [Preprint]. 2024 Oct 2:2024.09.25.614780. doi: 10.1101/2024.09.25.614780.ABSTRACTWe report the first implementation of ion mobility mass spectrometry combined with an ultra-high throughput sample introduction technology for high throughput screening (HTS). The system integrates differential ion mobility (DMS) with acoustic ejection mass spectrometry (AEMS), termed DAEMS, enabling the simultaneous quantitation of structural isomers that are the sub-strates and products of isomerase mediated reactions in intermediary metabolism. We demonstrate this potential by comparing DAEMS to a luminescence assay for the isoform of phosphoglycerate mutase (iPGM) distinctively present in pathogens offering an opportunity as a drug target for a variety of microbial and parasite borne diseases. The metabolome consists of many structural isomers that require for separation a mobility resolving power of more than 300. Resolving powers measured in collision cross section space of 1588 and 1948 for 2- and 3-phosphoglycerate and the citrate/isocitrate isomeric pairs respectively are shown. These are the highest reported ion mobility resolving powers for molecules from the metabolome reported to date. The potential for DAEMS as a generalized screening tool is demonstrated with the separation of the substrates and products of two additional isomerases that present as potential therapeutic targets, chorismate mutase and triosephosphate isomerase. The separations are achieved at speeds compatible with the sample introduction rates of AEMS providing sufficient data points to integrate the peaks for quantitation without the use of internal standards. DMS hyphenated with acoustic sample ejection MS provides a unique solution to high throughput mass spectrom-etry applications where isomer and other types of separations are required.PMID:39803517 | PMC:PMC11722233 | DOI:10.1101/2024.09.25.614780

Bio Protoc. 2025 Jan 5;15(1):e5154. doi: 10.21769/BioProtoc.5154. eCollection 2025 Jan 5.ABSTRACTCucumber (Cucumis sativus) trichomes play a critical role in resisting external biological and abiotic stresses. Glandular trichomes are particularly significant as they serve as sites for the synthesis and secretion of secondary metabolites, while non-glandular trichomes are pivotal for determining the appearance quality of cucumbers. However, current methods for separating trichomes encounter challenges such as low efficiency and insufficient accuracy, limiting their applicability in multi-omics sequencing studies. This protocol introduces an efficient system designed for the precise separation of glandular and non-glandular trichomes from cucumber fruit. The process begins with the pre-cooling of sorbitol buffer or ethanol solution and the RNA-free treatment of laboratory supplies, followed by sterilization and pre-cooling. After filling glass bottles with pre-cooling buffer and glass beads, cucumber ovaries are then placed in the glass bottles and the trichome is harvested by bead-beating method. The separation process involves sequential filtration through various steel sieves and centrifugation to separate trichomes. The separated trichomes obtained from this method are well-suited for subsequent multi-omics sequencing analyses. This protocol achieved high precision in separating glandular and non-glandular trichomes, significantly enhancing the efficiency of separation and sample collection processes. This advancement not only addresses existing limitations but also facilitates comprehensive studies aimed at exploring the genetic and biochemical diversity present within cucumber trichomes, thereby opening avenues for broader agricultural and biological research applications. Key features • Use cucumber fruits on the day of flowering. • Pre-cooling and RNA-free treatment ensure supply quality and purity. • Efficiently separate glandular and non-glandular trichomes. • Trichome samples are suitable for multi-omics sequencing analysis.PMID:39803323 | PMC:PMC11717712 | DOI:10.21769/BioProtoc.5154

Food Sci Nutr. 2025 Jan 9;13(1):e4726. doi: 10.1002/fsn3.4726. eCollection 2025 Jan.ABSTRACTAmomum tsaoko is an important spice and medicinal plant widely utilized in East and Southeast Asia. Non-targeted metabolomics techniques were employed to study the variations in the content and composition of essential oil from A. tsaoko during drying at different temperatures: 40°C, 50°C, 60°C, and 70°C. A total of 260 metabolites were detected using gas chromatography-mass spectrometry (GC-MS), mainly terpenoids and aldehydes. Cineole, the most important component, accumulated abundantly in samples dried at 50°C. A higher temperature (70°C) was conducive to the accumulation of aldehydes. Overall, the optimal drying condition for A. tsaoko was determined to be 50°C for 50 h. In addition, nine differential metabolites were screened using variable important in projection and p value (VIP > 1 and p < 0.05), which may serve as potential flavor markers to differentiate various drying treatments of A. tsaoko. This study provides a novel perspective on understanding the dynamic metabolites changes during the drying process, and establishes a theoretical foundation for the refinement and high-quality processing of A. tsaoko.PMID:39803287 | PMC:PMC11717005 | DOI:10.1002/fsn3.4726

Food Sci Nutr. 2024 Dec 30;13(1):e4656. doi: 10.1002/fsn3.4656. eCollection 2025 Jan.ABSTRACTAlzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system. The interplay between the intestinal microbiota and metabolites is believed to influence brain function and the pathogenesis of neurodegenerative conditions through the microbe-gut-brain axis. Sika deer antler protein possesses neuroprotective properties; however, the precise mechanism by which it improves AD remains unclear. Sika deer antler protein ameliorated AD in vivo by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. The metabolome of brain and intestinal tissues and the microbiota of intestinal contents were tested and analyzed according to the microbe-gut-brain theory. Sika deer antler protein increased beneficial bacterial levels and decreased harmful bacterial levels. Correlation analyses using the gut flora-metabolomics pathway ultimately revealed that sika deer antler protein modulated the brain and intestinal tract bi-directionally via the tyrosine metabolism pathway, thereby establishing a connection within the microbe-gut-brain axis. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the differential metabolite targets of the DAP4 group showed that the enriched pathways mainly included PI3K/AKT, which was consistent with the findings of the pharmacodynamic mechanisms observed in in vivo experiments. This suggests that antler protein may be involved in microbe-gut-brain interactions through tyrosine metabolism and may improve AD by activating the PI3K/AKT/Nrf2 signaling pathway. These findings add to our understanding of the microbe-gut-brain axis facilitated by sika deer antler protein and offer novel insights for further research on sika deer antler protein in alleviating AD.PMID:39803278 | PMC:PMC11717054 | DOI:10.1002/fsn3.4656

Food Sci Nutr. 2025 Jan 9;13(1):e4624. doi: 10.1002/fsn3.4624. eCollection 2025 Jan.ABSTRACTSarcopenia (SP), an age-associated condition marked by muscle weakness and loss has been strongly connected with metabolic factors according to substantial evidence. Nevertheless, the causal correlation between SP and serum metabolites, and the biological signaling pathways involved, is still not well understood. We performed a bidirectional two-sample Mendelian randomization (MR) analysis to examine the causal relationships between 1091 levels and 309 ratios of metabolites with SP traits, alongside investigating the relevant biological signaling pathways. Additionally, we explored the differential expression of plasma metabolites and potential biological signaling pathways in an animal model of SP. When SP was utilized as the outcome, we identified 11 robust causal associations between seven metabolite levels/ratios and SP-related traits using Bonferroni's correction (threshold: p < 0.05). We verified the stable causal association of glycine levels and SP in the validation. As for the reverse MR analysis, there were 11 strong causal relationships with 11 plasma metabolite levels/ratios remaining after multiple contrast correction. Additionally, biological signaling pathway analysis showed that glycine metabolism, insulin resistance, and cAMP signaling pathways may contribute to the connection between metabolites and SP. Mendelian validation of various datasets and observations in animal serum metabolomics suggests a strong association between glycine metabolism and SP. Our results indicate that the identified metabolites and biosignaling pathways could serve as important circulatory metabolic biomarkers for the screening and prevention of SP in clinical settings. Additionally, they represent potential molecules for future exploration of mechanisms and selection of drug targets.PMID:39803274 | PMC:PMC11717068 | DOI:10.1002/fsn3.4624

Food Sci Nutr. 2025 Jan 12;13(1):e4695. doi: 10.1002/fsn3.4695. eCollection 2025 Jan.ABSTRACTThis study evaluates the therapeutic impact of Fructus aurantii (FA) stir-baked with tartary buckwheat bran (TBB) on functional dyspepsia (FD), employing a reserpine at the dose of 5 mg/kg to rats. FA, a traditional Chinese herbal medicine, is processed with TBB to enhance its gastrointestinal motility benefits. The study's objectives were to assess the impact of this preparation on intestinal flora, SCFA levels, and metabolomic profiles in FD. Rats were divided into groups receiving different treatments, with the TBB-FA group showing a 7.15-33.2 times increase in fecal SCFA levels, specifically propionate and butyrate, compared to the Fructus aurantii (FA) stir-baked with wheat bran (WB) group (WB-FA) (p < 0.05). Metabolomics identified 23 serum and 11 intestinal mucosal biomarkers associated with FD, predominantly linked to the purine metabolic pathway. Results indicated a significant positive correlation (r ≥ 0.7) between the abundance of Bacteroides and the expression of propionate and isobutyrate in fecal samples post-TBB-FA treatment. This suggests that TBB-FA may enhance beneficial gut bacteria and SCFA production, potentially modulating the purinergic signaling pathway, which is implicated in gastrointestinal motility. In conclusion, the study demonstrates that TBB-FA could be a promising therapeutic approach for FD by improving gut microbiota and SCFA levels and highlights the purinergic signaling pathway as a novel target for treatment. The findings pave the way for further research into the integration of traditional Chinese medicine and modern therapeutic strategies for FD.PMID:39803263 | PMC:PMC11725054 | DOI:10.1002/fsn3.4695

Food Sci Nutr. 2024 Dec 5;13(1):e4637. doi: 10.1002/fsn3.4637. eCollection 2025 Jan.ABSTRACTCamellia seed oil (CSO), a potential prebiotic agent, can significantly increase the relative abundance of Akkermansia muciniphila (A. muciniphila) in mice gut microbiota following oral administration, this study aims to investigate the enhancing effect in vitro. The results showed that after 24-h co-cultivation with 0.5% (v/v) CSO, the growth of A. muciniphila increased from 11.61 ± 0.04 Log10CFU/mL to 12.17 ± 0.10 Log10CFU/mL (p < 0.05), accompanied by a reduction in the oxidation-reduction potential (ORP) value of the media from -126.67 ± 1.78 mV to -117.33 ± 0.72 mV (p < 0.05). Additionally, squalene and (+)-α-tocopherol, bioactive compounds present in CSO, were found to promote A. muciniphila proliferation (squalene OD600: 1.086 ± 0.002, tocopherol OD600: 1.100 ± 0.003, DMSO control OD600: 0.991 ± 0.003, p < 0.0001). Transcriptomic and metabolomic profiling revealed 464, 121, and 194 differentially expressed genes (DEGs) and 212, 160, and 156 differentially expressed metabolites (DEMs) in A. muciniphila co-cultivated with CSO after 4, 16, and 24 h, respectively (p < 0.05). The upregulated DEGs and DEMs were primarily enriched in pathways associated with energy generation (e.g., gap, icd, sucC, GOZ73_RS04175, succinate, phosphoenolpyruvate), nucleotide metabolism (e.g., mazG, deoxyguanosine), amino acid metabolism (e.g., argF, metK, L-tyrosine), translation (e.g., rplO, rpmC), and environmental adaptation (e.g., murA, katE, reduced nicotinamide adenine dinucleotide). These findings suggest that various bioactive compounds present in CSO exhibit prebiotic effects on the in vitro proliferation of A. muciniphila by facilitating nutrient utilization and environmental adaptation. This study provides insights into the extended utilization of CSO.PMID:39803248 | PMC:PMC11717052 | DOI:10.1002/fsn3.4637

Food Sci Nutr. 2024 Dec 6;13(1):e4651. doi: 10.1002/fsn3.4651. eCollection 2025 Jan.ABSTRACTDendrobium officinale is a kind of popular functional food to be consumed by both healthy and diabetic people. As its major constituent, D. officinale polysaccharide (DOP) is mainly utilized by gut microbiota. Despite distinctive gut microbiota composition between healthy and diabetic individuals, no study compared the interplay between DOP and gut microbiota under healthy and diabetic status. The current study aims to investigate and compare the metabolic signatures and regulatory potential of DOP on gut microbiota between healthy and diabetic status. Our serial in vitro fermentation investigations found that mannose in DOP was more utilized by gut microbiota under diabetic status with higher production of propanoic acid and lower production of butyric acid compared with those under healthy status. Moreover, metabolomic analyses revealed different impacts of DOP on intestinal microbial metabolites between healthy and diabetic status with upregulating taurine and downregulating 2-hydroxybutyric acid only occurring under diabetic status. Biodiversity analyses demonstrated that DOP treatment could only significantly improve the diversity of gut microbiota under diabetic status while there was no significant effect on that under healthy status. Further gut microbiota composition analyses indicated that DOP treatment could promote probiotics (Dubosiella, Bifidobacterium, and Akkermansia) under both healthy and diabetic status while inhibit pathogens (Escherichia-Shigella) only under diabetic status. In summary, our current insights into metabolic signatures and regulatory effects of DOP in the gut microbiota under healthy and diabetic status provided scientific evidence for its broad use as functional food.PMID:39803214 | PMC:PMC11717035 | DOI:10.1002/fsn3.4651

JHEP Rep. 2024 Sep 30;7(1):101228. doi: 10.1016/j.jhepr.2024.101228. eCollection 2025 Jan.ABSTRACTBACKGROUND & AIMS: The role of infiltrating neutrophils in hepatocellular carcinoma (HCC) is modulated by cellular metabolism, specifically lipid homeostasis. Throughout the progression of HCC, alterations in lipid metabolism are intricately linked with regulation of neutrophil function and the release of neutrophil extracellular traps (NETs). However, how much the protumor effect of a high-fat diet (HFD) depends on NETs and the potential interplay between NETs and other leukocytes in HCC remains uncertain.METHODS: In this study, the molecular mechanism of NET release and the potential beneficial effects of PPARα agonists on the HCC microenvironment were explored through proteomics, metabolomics, tissue microarray, immunofluorescence, flow cytometry, western blot, and dual-luciferase reporter gene assays (n = 6 per group).RESULTS: Our study demonstrated a notable inhibition of PPARα signaling in HCC. Furthermore, the disruption of PPARα-mediated lipid metabolism was responsible for the release of NETs. The presence of a HFD was observed to induce mitochondrial impairment in neutrophils, leading to the activation of cGAS-STING by oxidized mitochondrial DNA (Ox-mtDNA). Consequently, this activation triggered the release of NETs containing Ox-mtDNA through the enhancement of NLRP3-GSDMD-N in a NF-κB-dependent manner. Moreover, the release of NETs within HCC tissues effectively isolated cytotoxic leukocytes in the outer regions of HCC.CONCLUSIONS: Our study not only provides insight into the relationship between lipid metabolism disorders and NETs' tumor-promoting function, but also provides an important strategic reference for multi-target or combined immunotherapy of HCC.IMPACT AND IMPLICATIONS: We have identified PPARα and its agonists as therapeutic targets for controlling the neutrophil extracellular traps associated with high lipid metabolism. Results from preclinical models suggest that PPARα can limit mitochondrial oxidative stress, inhibit cGAS-STING-NF-κB signaling, and limit the release of neutrophil extracellular traps, thereby increasing the contact of anti-tumor leukocytes and hepatocellular cancer cells and limiting tumor growth.PMID:39802808 | PMC:PMC11719391 | DOI:10.1016/j.jhepr.2024.101228

Front Microbiol. 2024 Dec 27;15:1470193. doi: 10.3389/fmicb.2024.1470193. eCollection 2024.ABSTRACTLong COVID is an often-debilitating condition with severe, multisystem symptoms that can persist for weeks or months and increase the risk of various diseases. Currently, there is a lack of diagnostic tools for Long COVID in clinical practice. Therefore, this study utilizes plasma proteomics and metabolomics technologies to understand the molecular profile and pathophysiological mechanisms of Long COVID, providing clinical evidence for the development of potential biomarkers. This study included three age- and gender-matched cohorts: healthy controls (n = 18), COVID-19 recovered patients (n = 17), and Long COVID patients (n = 15). The proteomics results revealed significant differences in proteins between Long COVID-19 patients and COVID-19 recovered patients, with dysregulation mainly focused on pathways such as coagulation, platelets, complement cascade reactions, GPCR cell signal transduction, and substance transport, which can participate in regulating immune responses, inflammation, and tissue vascular repair. Metabolomics results showed that Long COVID patients and COVID-19 recovered patients have similar metabolic disorders, mainly involving dysregulation in lipid metabolites and fatty acid metabolism, such as glycerophospholipids, sphingolipid metabolism, and arachidonic acid metabolism processes. In summary, our study results indicate significant protein dysregulation and metabolic abnormalities in the plasma of Long COVID patients, leading to coagulation dysfunction, impaired energy metabolism, and chronic immune dysregulation, which are more pronounced than in COVID-19 recovered patients.PMID:39802657 | PMC:PMC11718655 | DOI:10.3389/fmicb.2024.1470193

Curr Res Food Sci. 2024 Dec 15;10:100959. doi: 10.1016/j.crfs.2024.100959. eCollection 2025.ABSTRACTModified Atmosphere Packaging (MAP) is a conventional method used to prolong the shelf-life of fresh-cut vegetables, including lettuce. However, MAP-stored lettuce remains perishable, and its deterioration mechanism is not fully understood. Here, we utilized non-targeted LC-MS metabolomics to evaluate the effects of cutting and extended storage time on metabolite profiles of lettuce stored in MAP. Additionally, hyperspectral imaging was used to measure perceptual changes. Our findings reveal a bipartite response to wounding. In early storage, enzymatic browning was the main response to wounding, evidenced by accumulation of caffeic acid derivatives and flavonoids, substrates for polyphenol oxidases. As storage progressed, enzymatic browning was inhibited, and a shift towards lignification became apparent, evidenced by accumulation of monolignol derivatives. These findings offer new insights into the deterioration mechanism of fresh-cut lettuce occurring in MAP.PMID:39802646 | PMC:PMC11721850 | DOI:10.1016/j.crfs.2024.100959

J Mol Cell Cardiol Plus. 2023 Sep 19;6:100050. doi: 10.1016/j.jmccpl.2023.100050. eCollection 2023 Dec.ABSTRACTBACKGROUND AND AIM: Phenotypic expression of hypertrophic cardiomyopathy (HCM) and disease course are associated with unfavorable metabolic health. We investigated if Western diet (WD) feeding is sufficient to trigger cardiac hypertrophy and dysfunction in heterozygous (HET) Mybpc3 c.772G>A knock-in mice.METHODS AND RESULTS: Wild-type (WT) and HET mice (3-months-old) were fed a WD or normal chow (NC) for 8 weeks. Metabolomic analyses on serum revealed systemic metabolic derailment in WD-fed WT and HET mice. Strikingly, only WD-fed HET mice developed cardiac hypertrophy and dysfunction, which was not driven by aggravated cardiac myosin binding protein-C haploinsufficiency. WD reduced oxidative phosphorylation and increased toxic lipids in the heart irrespective of genotype. Cardiac proteomic analyses revealed higher abundance of proteins involved in fatty acid oxidation in WD-fed mice, however this increase was blunted in HET compared to WT mice. Accordingly, cardiac metabolomic and lipidomic analyses showed accumulation of acylcarnitines in WD-fed HET vs WT mice.CONCLUSION: WD feeding triggered cardiac dysfunction and hypertrophy in otherwise phenotype-negative HET Mybpc3 c.772G>A mice. We propose that the presence of a HCM mutation predisposes the heart to metabolic inflexibility when subjected to systemic metabolic stress. Our study represents a novel approach to study the interplay between unfavorable metabolic health and mutation-induced defects in HCM disease development.PMID:39802622 | PMC:PMC11708371 | DOI:10.1016/j.jmccpl.2023.100050

Mol Genet Metab Rep. 2024 Dec 16;42:101172. doi: 10.1016/j.ymgmr.2024.101172. eCollection 2025 Mar.ABSTRACTDihydrolipoamide dehydrogenase (DLD) deficiency is an autosomal recessive disorder characterized by a functional disruption in several critical mitochondrial enzyme complexes, including pyruvate dehydrogenase and α-ketoglutarate dehydrogenase. Despite DLD's pivotal role in cellular energy metabolism, detailed molecular and metabolic consequences of DLD deficiency (DLDD) remain poorly understood. This study represents the first in-depth multi-omics analysis, specifically metabolomic and transcriptomic, of fibroblasts derived from a DLD-deficient patient compound heterozygous for a common Ashkenazi Jewish variant (c.685G > T) and a novel North African variant (c.158G > A). The investigation reveals significant metabolic disruptions that distinguish the cellular phenotype of DLDD from other metabolic disorders and healthy controls. Employing a range of cellular and molecular techniques, including live-cell imaging, mitochondrial activity assays, immunofluorescence, transcriptomics and metabolomic analysis, we compared DLDD fibroblasts with fibroblasts from glycogen storage disease type 1 A (GSD1a) patients and healthy controls (HC) subjects. Our metabolomics analysis identified significant alterations in mitochondrial metabolism, particularly reduced glycine cleavage, altered one carbon metabolism and serine catabolism. Transcriptome profiling highlighted dysregulation in genes associated with metabolic stress and mitochondrial dysfunction. Our findings highlight reduced mitochondrial activity and respiratory capacity in DLDD fibroblasts, similar to observations in GSD1a fibroblasts. This multi-omics approach not only advances our understanding of the pathophysiology of DLDD, but also illustrates the potential for developing targeted diagnostics and therapeutic strategies.PMID:39802097 | PMC:PMC11719413 | DOI:10.1016/j.ymgmr.2024.101172

Heliyon. 2024 Dec 10;11(1):e41019. doi: 10.1016/j.heliyon.2024.e41019. eCollection 2025 Jan 15.ABSTRACTThe human deoxyribonucleoside triphosphatase (dNTPase) Sterile alpha motif and histidine-aspartate domain containing protein 1 (SAMHD1) has a dNTPase-independent role in repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). Here, we show that VENOSA4 (VEN4), the probable Arabidopsis thaliana ortholog of SAMHD1, also functions in DSB repair by HR. The ven4 loss-of-function mutants showed increased DNA ploidy and deregulated DNA repair genes, suggesting DNA damage accumulation. Hydroxyurea, which blocks DNA replication and generates DSBs, induced VEN4 expression. The ven4 mutants were hypersensitive to hydroxyurea, with decreased DSB repair by HR. Metabolomic analysis of the strong ven4-0 mutant revealed depletion of metabolites associated with DNA damage responses. In contrast to SAMHD1, VEN4 showed no evident involvement in preventing R-loop accumulation. Our study thus reveals functional conservation in DNA repair by VEN4 and SAMHD1.PMID:39801971 | PMC:PMC11720913 | DOI:10.1016/j.heliyon.2024.e41019