PubMed

Heliyon. 2024 Mar 2;10(5):e27061. doi: 10.1016/j.heliyon.2024.e27061. eCollection 2024 Mar 15.ABSTRACTDendrobium officinale is an important traditional Chinese medicinal herb containing bioactive polysaccharides and alkaloids. This study characterized metabolite differences between jiaosu (fermented plant product) from Dendrobium flowers versus stems using untargeted metabolomics. The jiaosu was fermented by mixed fermentation of Saccharomyces cerevisiae, Lactobacillus bulgaricus and Streptococcus thermophilus. Liquid chromatography-mass spectrometry analysis identified 476 differentially expressed metabolites between the two Jiaosu products. Key results showed downregulation of flavonoid metabolism in Dendrobium Stems Edible Plant Jiaosu (SEP) but increased flavonoid synthesis in Dendrobium Flowers Edible Plant Jiaosu (FEP), likely an antioxidant response. SEP displayed upregulation of lignin metabolites with potential antioxidant properties. The findings demonstrate significant metabolite profile differences between SEP and FEP, providing the basis for developing functional jiaosu products targeting specific health benefits.PMID:38463789 | PMC:PMC10923680 | DOI:10.1016/j.heliyon.2024.e27061

Heliyon. 2024 Feb 29;10(5):e26813. doi: 10.1016/j.heliyon.2024.e26813. eCollection 2024 Mar 15.ABSTRACTBACKGROUND: Previous studies offer inconclusive results on the association between diet-derived circulating antioxidants and epilepsy.OBJECTIVE: This study aims to assess oxidative stress presence in epilepsy patients' circulation and investigate the causal link between diet-derived circulating antioxidants and epilepsy.METHODS: Untargeted metabolomics analysis was conducted on plasma samples from 62 epileptic patients and 20 healthy individuals to evaluate oxidative stress based on metabolite alterations in epilepsy patients' circulation. Two-sample Mendelian Randomization (MR) analysis examined the causation between diet-derived circulating antioxidants (measured by absolute levels and relative metabolite concentrations) and epilepsy, utilizing the inverse-variance weighted (IVW) method as the primary outcome, with complementary MR analysis methods (MR Egger, weighted median, weighted mode, and simple mode).RESULTS: Untargeted metabolomics analysis revealed elevated circulating oxidizing metabolites (palmitic acid, oleic acid, linoleic acid, and myristic acid) and reduced reducing metabolites (glutamine) in epilepsy patients, providing robust evidence of oxidative stress. The IVW analysis indicated significantly reduced epilepsy risk (odds ratio: 0.552; 95% confidence interval: 0.335-0.905, P = 0.018) with genetically determined higher absolute circulating β-carotene. However, other diet-derived circulating antioxidants (lycopene, retinol, ascorbic acid, and selenium) and antioxidant metabolites (α-tocopherol, γ-tocopherol, ascorbic acid, and retinol) did not significantly associate with epilepsy risk. Additional MR analysis methods and heterogeneity assessments confirmed the results' robustness.CONCLUSION: This study provides compelling evidence of oxidative stress in epilepsy patients' circulation. However, the majority of diet-derived circulating antioxidants (lycopene, retinol, ascorbic acid, vitamin E, and selenium) are unlikely to causally associate with reduced epilepsy risk, except for β-carotene.PMID:38463786 | PMC:PMC10920176 | DOI:10.1016/j.heliyon.2024.e26813

EPMA J. 2024 Feb 27;15(1):1-23. doi: 10.1007/s13167-024-00356-6. eCollection 2024 Mar.ABSTRACTWorldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990-2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep-wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurate data interpretation performed by the multiparametric analysis. Aspects presented in the paper include the needs of young populations and elderly, personalised risk assessment in primary and secondary care, cost-efficacy, application of innovative technologies and screening programmes, advanced education measures for professionals and general population-all are essential pillars for the paradigm change from reactive medical services to 3PM in the overall IS management promoted by the EPMA.PMID:38463624 | PMC:PMC10923756 | DOI:10.1007/s13167-024-00356-6

Front Plant Sci. 2024 Feb 23;15:1333989. doi: 10.3389/fpls.2024.1333989. eCollection 2024.ABSTRACTDendrobium is a perennial herb found in Asia that is known for its medicinal and ornamental properties. Studies have shown that the stem is the primary medicinal component of Dendrobium spp. To investigate the effect of the species and age of Dendrobium (in years) on the content of its medicinal components, we collected the stems of 1-to-4-year-old D. officinale, D. moniliforme, and D. huoshanense, sequenced the transcriptome, metabolome, and microbiome, and analyzed the data in a comprehensive multi-omics study. We identified 10,426 differentially expressed genes (DEGs) with 644 differentially accumulated metabolites (DAMs) from 12 comparative groups and mapped the flavonoid pathway based on DEGs and DAMs. Transcriptomic and metabolomic data indicated a general trend of the accumulation of flavonoids exhibiting pharmacological effects in the three Dendrobium species. In addition, joint metabolome and microbiome analyses showed that actinobacteria was closely associated with flavonoid synthesis with increasing age. Our findings provide novel insights into the interactions of flavonoids of Dendrobium with the transcriptome and microbiome.PMID:38463561 | PMC:PMC10920241 | DOI:10.3389/fpls.2024.1333989

Front Genet. 2024 Feb 23;15:1360138. doi: 10.3389/fgene.2024.1360138. eCollection 2024.ABSTRACTBackground: Litchi (Litchi chinensis) is an important sub-tropical fruit in the horticulture market in China. Breeding for improved fruit characteristics is needed for satisfying consumer demands. Budding is a sustainable method for its propagation. During our ongoing breeding program, we observed a litchi mutant with flat leaves and sharp fruit peel cracking in comparison to the curled leaves and blunt fruit peel cracking fruits of the mother plant. Methods: To understand the possible molecular pathways involved, we performed a combined metabolome and transcriptome analysis. Results: We identified 1,060 metabolites in litchi leaves and fruits, of which 106 and 101 were differentially accumulated between the leaves and fruits, respectively. The mutant leaves were richer in carbohydrates, nucleotides, and phenolic acids, while the mother plant was rich in most of the amino acids and derivatives, flavonoids, lipids and organic acids and derivatives, and vitamins. Contrastingly, mutant fruits had higher levels of amino acids and derivatives, carbohydrates and derivatives, and organic acids and derivatives. However, the mother plant's fruits contained higher levels of flavonoids, scopoletin, amines, some amino acids and derivatives, benzamidine, carbohydrates and derivatives, and some organic acids and derivatives. The number of differentially expressed genes was consistent with the metabolome profiles. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway-enriched gene expressions showed consistent profiles as of metabolome analysis. Conclusion: These results provide the groundwork for breeding litchi for fruit and leaf traits that are useful for its taste and yield.PMID:38463170 | PMC:PMC10920226 | DOI:10.3389/fgene.2024.1360138

J Food Sci. 2024 Mar 10. doi: 10.1111/1750-3841.16973. Online ahead of print.ABSTRACTFermented foods have shown promise in preventing or treating ulcerative colitis (UC) via regulating intestinal flora and correcting metabolic disorders. However, the prevention effect of fermented Wallace melon juice (FMJ) on UC is unclear. In this study, the effects of FMJ on dextran sodium sulfate (DSS)-induced UC were investigated via 16S rRNA sequencing and non-targeted metabolomics. The results showed that FMJ was effective in alleviating the symptoms of UC, reducing histological damage and oxidative stress, decreasing the levels of pro-inflammatory cytokines. After FMJ treatment, the level of propionic acid, butyric acid, and valeric acid increased by 14.1%, 44.4%, and 52.4% compared to DSS-induced UC mice. Meanwhile, the levels of harmful bacteria such as Oscillospira, Bacteroidetes, and Erysipelotrichaceae and Clostridium decreased, while the levels of beneficial bacteria such as Akkermansia, Lactobacillus, and Bifidobacterium increased. Fecal metabolomics analysis identified 31 differential metabolites, which could regulate metabolic disorders in UC mice by controlling the primary bile acid biosynthesis, purine metabolism, and pantothenate and CoA biosynthesis pathway. Additionally, the abundances of butyric acid, bile acids, and pantothenic acid were positively correlated with Allobaculum, Bifidobacterium, and other beneficial bacteria (R2 > 0.80, p < 0.01). The results indicated that FMJ played a role in regulating the structure of intestinal flora, which in turn helped in repairing metabolic disorders and alleviated colitis inflammation.PMID:38462851 | DOI:10.1111/1750-3841.16973

Crit Rev Anal Chem. 2024 Mar 10:1-27. doi: 10.1080/10408347.2024.2312502. Online ahead of print.ABSTRACTBoswellia resin is an exudate from the cut bark of Boswellia trees. The main constituents of pharmacological interest are boswellic acids (pentacyclic triterpenoids), namely α-boswellic acid, β-boswellic acid, 3-O-acetyl-α-boswellic acid, 3-O-acetyl-β-boswellic acid, 11-keto-β-boswellic acid, and 3-O-acetyl-11-keto-β-boswellic acid. Nowadays, dietary supplements with Boswellia serrata extract are used in the treatment of inflammatory joint diseases. Additionally, the constituents of Boswellia resin have shown potential for the treatment of other chronic inflammatory diseases and various types of cancer. Separation methods including ultra/high-performance liquid chromatography, gas chromatography, thin layer chromatography, supercritical fluid chromatography, and capillary electrochromatography coupled with UV or MS detection have been used for the determination of boswellic acids in various matrices (mostly plant material and biological samples). This review aims to provide a comprehensive summary of these separation methods, offering a critical discussion of their strengths and limitations in the analysis of boswellic acids. The knowledge of various separation methods plays a pivotal role in the quality control of herbal dietary supplements and the monitoring of the metabolism and pharmacokinetics of their constituents. The approaches based on metabolomics and network pharmacology represent new ways of fingerprinting secondary metabolites in Boswellia resin increasing the comprehensiveness of the output of these methods resulting in safer dietary supplements.PMID:38462842 | DOI:10.1080/10408347.2024.2312502

Acta Physiol (Oxf). 2024 Mar 10:e14130. doi: 10.1111/apha.14130. Online ahead of print.ABSTRACTAIM: Prolonged high-fat diet (HFD) consumption has been shown to impair cognition and depression. The combined effects of HFD and lipopolysaccharide (LPS) administration on those outcomes have never been thoroughly investigated. This study investigated the effects of LPS, HFD consumption, and a combination of both conditions on microglial dysfunction, microglial morphological alterations, synaptic loss, cognitive dysfunction, and depressive-like behaviors.METHODS: Sixty-four male Wistar rats were fed either a normal diet (ND) or HFD for 12 weeks, followed by single dose-subcutaneous injection of either vehicle or LPS. Then, cognitive function and depressive-like behaviors were assessed. Then, rats were euthanized, and the whole brain, hippocampus, and spleen were collected for further investigation, including western blot analysis, qRT-PCR, immunofluorescence staining, and brain metabolome determination.RESULTS: HFD-fed rats developed obese characteristics. Both HFD-fed rats with vehicle and ND-fed rats with LPS increased cholesterol and serum LPS levels, which were exacerbated in HFD-fed rats with LPS. HFD consumption, but not LPS injection, caused oxidative stress, blood-brain barrier disruption, and decreased neurogenesis. Both HFD and LPS administration triggered an increase in inflammatory genes on microglia and astrocytes, increased c1q colocalization with microglia, and increased dendritic spine loss, which were exacerbated in the combined conditions. Both HFD and LPS altered neurotransmitters and disrupted brain metabolism. Interestingly, HFD consumption, but not LPS, induced cognitive decline, whereas both conditions individually induced depressive-like behaviors, which were exacerbated in the combined conditions.CONCLUSIONS: Our findings suggest that LPS aggravates metabolic disturbances, neuroinflammation, microglial synaptic engulfment, and depressive-like behaviors in obese rats.PMID:38462756 | DOI:10.1111/apha.14130

Anal Chim Acta. 2024 Apr 15;1298:342400. doi: 10.1016/j.aca.2024.342400. Epub 2024 Feb 21.ABSTRACTBACKGROUND: Extracellular ATP is involved in disorders that cause inflammation of the airways and cough, thus limiting its release has therapeutic benefits. Standard luminescence-based ATP assays measure levels indirectly through enzyme degradation and do not provide a simultaneous readout for other nucleotide analogues. Conversely, mass spectrometry can provide direct ATP measurements, however, common RPLC and HILIC methods face issues because these molecules are unstable, metal-sensitive analytes which are often poorly retained. These difficulties have traditionally been overcome using passivation or ion-pairing chromatography, but these approaches can be problematic for LC systems. As a result, more effective analytical methods are needed.RESULTS: Here, we introduce a new application that uses microfluidic chip-based capillary zone electrophoresis-mass spectrometry (μCZE-MS) to measure ATP and its analogues simultaneously in biofluids. The commercially available ZipChip Interface and a High-Resolution Bare-glass microchip (ZipChip, HRB, 908 Devices Inc.) coupled to a Thermo Scientific Tribrid Orbitrap, were successfully used to separate and detect various nucleotide standards, as well as ATP, ADP, AMP, and adenosine in plasma and BALF obtained from naïve Brown Norway rats. The findings demonstrate that this approach can rapidly and directly detect ATP and its related nucleotide analogues, while also highlighting the need to preserve these molecules in biofluids with chelators like EDTA. In addition, we demonstrate that this μCZE-MS method is also suitable for detecting a variety of metabolites, revealing additional potential future applications.SIGNIFICANCE: This innovative μCZE-MS approach provides a robust new tool to directly measure ATP and other nucleotide analogues in biofluids. This can enable the study of eATP in human disease and potentially contribute to the creation of ATP-targeting therapies for airway illnesses.PMID:38462348 | DOI:10.1016/j.aca.2024.342400

Anim Sci J. 2024 Jan-Dec;95(1):e13925. doi: 10.1111/asj.13925.ABSTRACTIn this study, we characterized the effects of CT dietary inclusion at 2% (wt/wt) dry matter on the goat rumen metabolome and fermentation characteristics. Barley (BA) and corn (CN) were separately used as basal grain for the control rations, and rations supplemented with CT were BACT and CNCT, respectively. The rations were tested using eight Japanese Shiba × Saanen goats in a replicated 4 × 4 Latin square arrangement (28 days for each period). Ruminal fluid was obtained on day 25 of each period, and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis was performed. Metabolites from BACT against BA and CNCT against CN were mostly associated with purine metabolism. Moreover, BACT against BA showed intensified biosynthesis of unsaturated fatty acids, and CNCT against CN resulted in strengthened amino acid metabolism. Furthermore, strong correlations were observed between rumen NH3 -N and the copy number of total bacteria with most of the differential metabolites. The present paper provides a better understanding of the relationship between the rumen metabolome and fermentation characteristics and supports a shift in concern about using CT as a strategy to manipulate rumen metabolism.PMID:38462234 | DOI:10.1111/asj.13925

J Ethnopharmacol. 2024 Mar 8:118016. doi: 10.1016/j.jep.2024.118016. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Codonopsis pilosula (C. pilosula), also called "Dangshen" in Chinese, is derived from the roots of Codonopsis pilosula (Franch.) Nannf. (C. pilosula), Codonopsis pilosula var. Modesta (Nannf.) L.D.Shen (C. pilosula var. modesta) or Codonopsis pilosula subsp. Tangshen (Oliv.) D.Y.Hong (C. pilosula subsp. tangshen), is a well-known traditional Chinese medicine. It has been regularly used for anti-aging, strengthening the spleen and tonifying the lungs, regulating blood sugar, lowering blood pressure, strengthening the body's immune system, etc. However, the mechanism, by which, C. pilosula exerts its therapeutic effects on brain aging remains unclear.AIM OF THE STUDY: This study aimed to investigate the underlying mechanisms of the protective effects of C. pilosula water extract (CPWE) on the hippocampal tissue of D-galactose-induced aging mice.MATERIALS AND METHODS: In this research, plant taxonomy has been confirmed in the "The Plant List" database (www.theplantlist.org). First, an aging mouse model was established through the intraperitoneal injections of D-galactose solution, and low-, medium-, and high-dose CPWE were administered to mice by gavage for 42 days. Then, the learning and memory abilities of the mice were examined using the Morris water maze tests and step-down test. Hematoxylin and eosin staining was performed to visualize histopathological damage in the hippocampus. A transmission electron microscope was used to observe the ultrastructure of hippocampal neurons. Immunohistochemical staining was performed to examine the expression of glial fibrillary acidic protein (GFAP), the marker protein of astrocyte activation, and autophagy-related proteins, including microtubule-associated protein light chain 3 (LC3) and sequestosome 1 (SQSTM1)/p62, in the hippocampal tissues of mice. Moreover, targeted metabolomic analysis was performed to assess the changes in polar metabolites and short-chain fatty acids in the hippocampus.RESULTS: First, CPWE alleviated cognitive impairment and ameliorated hippocampal tissue damage in aging mice. Furthermore, CPWE markedly alleviated mitochondrial damage, restored the number of autophagosomes, and activated autophagy in the hippocampal tissue of aging mice by increasing the expression of LC3 protein and reducing the expression of p62 protein. Meanwhile, the expression levels of the brain injury marker protein GFAP decreased. Moreover, quantitative targeted metabolomic analysis revealed that CPWE intervention reversed the abnormal levels of L-asparagine, L-glutamic acid, L-glutamine, serotonin hydrochloride, succinic acid, and acetic acid in the hippocampal tissue of aging mice. CPWE also significantly regulated pathways associated with D-glutamine and D-glutamate metabolism, nitrogen metabolism, arginine biosynthesis, alanine, aspartate, and glutamate metabolisms, and aminoacyl-tRNA biosynthesis.CONCLUSIONS: CPWE could improve cognitive and pathological conditions induced by D-galactose in aging mice by activating autophagy and regulating metabolism, thereby slowing down brain aging.PMID:38462027 | DOI:10.1016/j.jep.2024.118016

J Ethnopharmacol. 2024 Mar 8:117989. doi: 10.1016/j.jep.2024.117989. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Massa Medicata Fermentata, a fermented Chinese medicine, is produced by the fermentation of six traditional Chinese medicines. Liu Shenqu (LSQ) and charred Liu Shenqu (CLSQ) have been used for strengthening the spleen and enhancing digestion for over a thousand years, and CLSQ is commonly used in clinical practice. However, it is unclear whether there is a difference in the spleen strengthening and digestion effects between LSQ and CLSQ, as well as their mechanisms of action.AIM OF STUDY: This study aims to compare the effects of LSQ and CLSQ on the digestive function of functional dyspepsia (FD) rats and reveal their mechanisms of action.MATERIALS AND METHODS: SPF grade SD rats were randomly divided into 6 groups: control group, model group, Liu Shenqu decoction low-dosage (LSQ LD) group, Liu Shenqu decoction high-dosage (LSQ HD) group, charred Liu Shenqu decoction low-dosage (CLSQ LD) group, and charred Liu Shenqu decoction high-dosage (CLSQ HD) group. Rats were injected intraperitoneally with reserpine to create an FD model and then treated by intragastric administration. During this period, record the weight and food intake of the animals. After 18 days of treatment, specimens of the gastric antrum, spleen, and duodenum of rats were taken for pathological staining and immunohistochemical detection of Ghrelin protein expression. Enzyme linked immunosorbent assay (ELISA) was used to determine the concentration of relevant gastrointestinal hormones in serum. The 16 S rDNA sequencing method was used to evaluate the effect of cecal contents on the structure of the gut microbiota in experimental rats. Plasma metabolomics analysis was performed using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-QTOF-MS) to further reveal their mechanism of action.RESULTS: LSQ and CLSQ improved the pathological tissue histological structure of FD rats and increased the levels of MTL and GAS hormones in serum and the levels of ghrelin in the gastric antrum, spleen, and duodenum, while reducing VIP, CCK, and SP hormone levels. The above results showed that the therapeutic efficacy of CLSQ is better than that of LSQ. Futhermore, the mechanism of action of LSQ and CLSQ were revealed. The 16 S rDNA sequencing results showed that both LSQ and CLSQ can improve the composition and diversity of the gut microbiota. And metabolomic analysis demonstrated that 20 metabolites changed after LSQ treatment, and 16 metabolites underwent continuous changes after CLSQ treatment. Further analysis revealed that LSQ mainly intervened in the metabolic pathways of glycerol phospholipid metabolism and arginine and proline metabolism, but CLSQ mainly intervened in the metabolic pathways of ether lipid metabolism, sphingolipid metabolism, and glycerophospholipid metabolism.CONCLUSIONS: Both LSQ and CLSQ can improve functional dyspepsia in FD rats, but CLSQ has a stronger improvement effect on FD. Although their mechanisms of action are all related to regulating gastrointestinal hormone secretion, significantly improving intestinal microbiota disorders, and improving multiple metabolic pathways, but the specific gut microbiota and metabolic pathways they regulate are different.PMID:38462026 | DOI:10.1016/j.jep.2024.117989

Sci Total Environ. 2024 Mar 8:171329. doi: 10.1016/j.scitotenv.2024.171329. Online ahead of print.ABSTRACTPhenolic compounds, abundant secondary metabolites in plants, profoundly influence soil ecosystems, plant growth, and interactions with herbivores. In this study, we explore the intricate relationships between phenolics, soil microbes, and gall formation in Ageratina adenophora (A. adenophora), an invasive plant species in China known for its allelopathic traits. Using metabolomic and microbial profiling, significant differences in soil microbial composition and metabolite profiles were observed between bulk and rhizosphere soil samples. Phenolics influenced bacterial communities, with distinct microbial populations enriched in each soil type. Additionally, phenolics impacted soil metabolic processes, with variations observed in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis between different soil treatments. Analysis of phenolic content in plant and soil samples revealed considerable variations, with higher concentrations observed in certain plant tissues and soil types. Bioactive phenols extracted from plant and soil samples were identified using gas chromatography/mass spectrometry (GC-MS), providing insights into the diverse chemical composition of these compounds. Furthermore, the effects of phenolics on plant growth and gall formation were investigated. Phenols exhibited both stimulatory and inhibitory effects on plant growth, with optimal concentrations promoting emergence but higher concentrations hindering growth. Gall formation was influenced by phenolic concentrations, leading to structural alterations in stem tissue and gall morphology. Histochemical analysis revealed starch and lipid accumulation in gall tissues, indicating metabolic changes induced by phenolics. The presence of phenolics disrupted tissue structures and influenced vascular bundle orientation in gall tissues. Overall, our study highlights the multifaceted roles of phenolic compounds in soil ecosystems, plant development, and gall formation, facilitating the utilization of secondary metabolites in agriculture.PMID:38462006 | DOI:10.1016/j.scitotenv.2024.171329

Sci Total Environ. 2024 Mar 8:171576. doi: 10.1016/j.scitotenv.2024.171576. Online ahead of print.ABSTRACTAmmonia pollution is an important environmental stress factors in water eutrophication. The intrinsic effects of ammonia stress on liver toxicity and muscle quality of rainbow trout were still unclear. In this study, we focused on investigating difference in muscle metabolism caused by metabolism disorder of rainbow trout liver at exposure times of 0, 3, 6, 9 h at 30 mg/L concentrations. Liver transcriptomic analysis revealed that short-term (3 h) ammonia stress inhibited carbohydrate metabolism and glycerophospholipid production but long-term (9 h) ammonia stress inhibited the biosynthesis and degradation of fatty acids, activated pyrimidine metabolism and mismatch repair, lead to DNA strand breakage and cell death, and ultimately caused liver damage. Metabolomic analysis of muscle revealed that ammonia stress promoted the reaction of glutamic acid and ammonia to synthesize glutamine to alleviate ammonia toxicity, and long-term (9 h) ammonia stress inhibited urea cycle, hindering the alleviation of ammonia toxicity. Moreover, it accelerated the consumption of flavor amino acids such as arginine and aspartic acid, and increased the accumulation of bitter substances (xanthine) and odorous substances (histamine). These findings provide valuable insights into the potential risks and hazards of ammonia in eutrophic water bodies subject to rainbow trout.PMID:38461997 | DOI:10.1016/j.scitotenv.2024.171576

Redox Biol. 2024 Mar 4;71:103112. doi: 10.1016/j.redox.2024.103112. Online ahead of print.ABSTRACTThe Warburg effect, also referred as aerobic glycolysis, is a common metabolic program during viral infection. Through targeted metabolomics combined with biochemical experiments and various cell models, we investigated the central carbon metabolism (CCM) profiles of cells infected with porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus with zoonotic potential. We found that PDCoV infection required glycolysis but decreased glycolytic flux, exhibiting a non-Warburg effect characterized by pyruvic acid accumulation. Mechanistically, PDCoV enhanced pyruvate kinase activity to promote pyruvic acid anabolism, a process that generates pyruvic acid with concomitant ATP production. PDCoV also hijacked pyruvic acid catabolism to increase biosynthesis of non-essential amino acids (NEAAs), suggesting that pyruvic acid is an essential hub for PDCoV to scavenge host energy and metabolites. Furthermore, PDCoV facilitated glutaminolysis to promote the synthesis of NEAA and pyrimidines for optimal proliferation. Our work supports a novel CCM model after viral infection and provides potential anti-PDCoV drug targets.PMID:38461791 | DOI:10.1016/j.redox.2024.103112

Environ Int. 2024 Mar 5;185:108559. doi: 10.1016/j.envint.2024.108559. Online ahead of print.ABSTRACTExposure to ozone has been associated with metabolic disorders in humans, but the underlying mechanism remains unclear. In this study, the role of the gut-liver axis and the potential mechanism behind the metabolic disorder were investigated by histological examination, microbiome and metabolome approaches in mice during the subacute (4-week) and subchronic (12-week) exposure to 0.5 ppm and 2.5 ppm ozone. Ozone exposure resulted in slowed weight gain and reduced hepatic lipid contents in a dose-dependent manner. After exposure to ozone, the number of intestinal goblet cells decreased, while the number of tuft cells increased. Tight junction protein zonula occludens-1 (ZO-1) was significantly downregulated, and the apoptosis of epithelial cells increased with compensatory proliferation, indicating a compromised chemical and physical layer of the intestinal barrier. The hepatic and cecal metabolic profiles were altered, primarily related to lipid metabolism and oxidative stress. The abundance of Muribaculaceae increased dose-dependently in both colon and cecum, and was associated with the decrease of metabolites such as bile acids, betaine, and L-carnitine, which subsequently disrupted the intestinal barrier and lipid metabolism. Overall, this study found that subacute and subchronic exposure to ozone induced metabolic disorder via disturbing the gut-liver axis, especially the intestinal barrier. These findings provide new mechanistic understanding of the health risks associated with environmental ozone exposure and other oxidative stressors.PMID:38461778 | DOI:10.1016/j.envint.2024.108559

J Huntingtons Dis. 2024 Mar 2. doi: 10.3233/JHD-231511. Online ahead of print.ABSTRACTBACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder caused by expanded cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene, resulting in the production of mutant huntingtin proteins (mHTT). Previous research has identified urea as a key metabolite elevated in HD animal models and postmortem tissues of HD patients. However, the relationship between disease course and urea elevations, along with the molecular mechanisms responsible for these disturbances remain unknown.OBJECTIVE: To better understand the molecular disturbances and timing of urea cycle metabolism across different stages in HD.METHODS: We completed a global metabolomic profile of cerebrospinal fluid (CSF) from individuals who were at several stages of disease: pre-manifest (PRE), manifest (MAN), and late manifest (LATE) HD participants, and compared to controls.RESULTS: Approximately 500 metabolites were significantly altered in PRE participants compared to controls, although no significant differences in CSF urea or urea metabolites were observed. CSF urea was significantly elevated in LATE participants only. There were no changes in the urea metabolites citrulline, ornithine, and arginine.CONCLUSIONS: Overall, our study confirms that CSF elevations occur late in the HD course, and these changes may reflect accumulating deficits in cellular energy metabolism.PMID:38461512 | DOI:10.3233/JHD-231511

Curr Microbiol. 2024 Mar 10;81(4):108. doi: 10.1007/s00284-024-03627-7.ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) infections have become one of the most threatening multidrug-resistant pathogens. Thus, an ongoing search for anti-MRSA compounds remains an urgent need to effectively treating MRSA infections. Phomopsidione, a novel antibiotic isolated from Diaporthe fraxini, has previously demonstrated potent anti-candidal activity. The present study aimed to investigate the effects of phomopsidione on the viability, virulence, and metabolites profile of MRSA. MRSA was sensitive to phomopsidione in a concentration-dependent manner. Phomopsidione exhibited minimum inhibitory concentration and minimum bactericidal concentration of 62.5 and 500.00 µg/mL against MRSA on broth microdilution assay. The compound showed significant reduction in virulence factors production including extracellular polymeric substances quantification, catalase, and lipase. An untargeted metabolomics analysis using liquid chromatography-high resolution mass spectrometry revealed a significant difference in the metabolites profile of MRSA with 13 putatively identified discriminant metabolites. The present study suggested the potential of phomopsidione as a promising anti-MRSA agent.PMID:38461425 | DOI:10.1007/s00284-024-03627-7

J Transl Med. 2024 Mar 9;22(1):259. doi: 10.1186/s12967-024-05028-7.ABSTRACTBACKGROUND: Amino acids (AAs) are one of the primary metabolic substrates for cardiac work. The correlation between AAs and both atrial fibrillation (AF) and aging has been documented. However, the relationship between AAs and age-related AF remains unclear.METHODS: Initially, the plasma AA levels of persistent AF patients and control subjects were assessed, and the correlations between AA levels, age, and other clinical indicators were explored. Subsequently, the age-related AF mouse model was constructed and the untargeted myocardial metabolomics was conducted to detect the level of AAs and related metabolites. Additionally, the gut microbiota composition associated with age-related AF was detected by a 16S rDNA amplicon sequencing analysis on mouse fecal samples.RESULTS: Higher circulation levels of lysine (Student's t-test, P = 0.001), tyrosine (P = 0.002), glutamic acid (P = 0.008), methionine (P = 0.008), and isoleucine (P = 0.014), while a lower level of glycine (P = 0.003) were observed in persistent AF patients. The feature AAs identified by machine learning algorithms were glutamic acid and methionine. The association between AAs and age differs between AF and control subjects. Distinct patterns of AA metabolic profiles were observed in the myocardial metabolites of aged AF mice. Aged AF mice had lower levels of Betaine, L-histidine, L-alanine, L-arginine, L-Pyroglutamic acid, and L-Citrulline compared with adult AF mice. Aged AF mice also presented a different gut microbiota pattern, and its functional prediction analysis showed AA metabolism alteration.CONCLUSION: This study provided a comprehensive network of AA disturbances in age-related AF from multiple dimensions, including plasma, myocardium, and gut microbiota. Disturbances of AAs may serve as AF biomarkers, and restoring their homeostasis may have potential benefits for the management of age-related AF.PMID:38461346 | DOI:10.1186/s12967-024-05028-7

Microbiome. 2024 Mar 9;12(1):49. doi: 10.1186/s40168-024-01774-4.ABSTRACTBACKGROUND: Aronia melanocarpa is a berry rich in polyphenols known for health benefits. However, the bioavailability of polyphenols has been questioned, and the individual taste acceptance of the fruit with its specific flavor varies. We recently observed substantial differences in the tolerability of aronia juice among healthy females, with half of the individuals tolerating aronia juice without complaints. Given the importance of the gut microbiome in food digestion, we investigated in this secondary analysis of the randomized placebo-controlled parallel intervention study (ClinicalTrials.gov registration: NCT05432362) if aronia juice tolerability was associated with changes in intestinal microbiota and bacterial metabolites, seeking for potential mechanistic insights into the impact on aronia polyphenol tolerance and metabolic outcomes.RESULTS: Forty females were enrolled for this 6-week trial, receiving either 100 ml natural aronia juice (verum, V) twice daily or a polyphenol-free placebo (P) with a similar nutritional profile, followed by a 6-week washout. Within V, individuals were categorized into those who tolerated the juice well (Vt) or reported complaints (Vc). The gut microbiome diversity, as analyzed by 16S rRNA gene-based next-generation sequencing, remained unaltered in Vc but changed significantly in Vt. A MICOM-based flux balance analysis revealed pronounced differences in the 40 most predictive metabolites post-intervention. In Vc carbon-dioxide, ammonium and nine O-glycans were predicted due to a shift in microbial composition, while in Vt six bile acids were the most likely microbiota-derived metabolites. NMR metabolomics of plasma confirmed increased lipoprotein subclasses (LDL, VLDL) post-intervention, reverting after wash out. Stool samples maintained a stable metabolic profile.CONCLUSION: In linking aronia polyphenol tolerance to gut microbiota-derived metabolites, our study explores adaptive processes affecting lipoprotein profiles during high polyphenol ingestion in Vt and examines effects on mucosal gut health in response to intolerance to high polyphenol intake in Vc. Our results underpin the importance of individualized hormetic dosing for beneficial polyphenol effects, demonstrate dynamic gut microbiome responses to aronia juice, and emphasize personalized responses in polyphenol interventions.PMID:38461313 | DOI:10.1186/s40168-024-01774-4