PubMed

Phenomics. 2024 Oct 8;4(5):525-526. doi: 10.1007/s43657-024-00177-7. eCollection 2024 Oct.NO ABSTRACTPMID:39723227 | PMC:PMC11666844 | DOI:10.1007/s43657-024-00177-7

Front Immunol. 2024 Dec 11;15:1450600. doi: 10.3389/fimmu.2024.1450600. eCollection 2024.ABSTRACTSalmonella enterica serovar Rissen (S. Rissen) is an emerging causative agent of foodborne diseases. The current emergence of antibiotic resistance makes necessary alternative therapeutic strategies. In this study, we investigated the potential of a phage-resistant strain of S. Rissen (RR) as a tool for developing an effective lipopolysaccharide (LPS)-based vaccine. The LPS O-antigen is known to play critical roles in protective immunity against Salmonella. However, the high toxicity of the LPS lipid A moiety limits its use in vaccines. Here, we demonstrated that the acquisition of bacteriophage resistance by S. Rissen leads to structural modifications in the LPS structure. Using NMR and mass spectrometry, we characterized the LPS from phage-resistant strains as a smooth variant bearing under-acylated Lipid A portions (penta- and tetra-acylated forms). We then combined RT-qPCR and NMR-based metabolomics to explore the effects of phage resistance and LPS modification on bacterial fitness and virulence. Finally, we conducted in vivo studies to determine whether lysogeny-induced remodeling of LPS affects the host immune response. Results revealed that the under-acylated variant of LPS from RR attenuates the inflammatory response in BALB/c mice, while eliciting a specific antibody response that protects against S. Rissen (RW) infection. In conclusion, our findings suggest that phage resistance, through lipid A modification, may offer a novel strategy for reducing LPS toxicity, highlighting its potential as a promising biological approach for developing LPS-based vaccines against Salmonella infections.PMID:39723217 | PMC:PMC11668645 | DOI:10.3389/fimmu.2024.1450600

Front Microbiol. 2024 Dec 11;15:1482925. doi: 10.3389/fmicb.2024.1482925. eCollection 2024.ABSTRACTINTRODUCTION: There are complex interactions between host and gut microbes during weaning, many of the mechanisms are not yet fully understood. Previous research mainly focuses on commercial pigs, whereas limited information has been known about the host and gut microbe interactions in miniature pigs.METHODS: To address the issue in Bama miniature piglets that were weaned 30 days after birth, we collected samples on days 25 and 36 for metabolomics, transcriptomics, and microgenomics analysis.RESULTS AND DISCUSSION: The average daily weight gain of piglets during weaning was only 58.1% and 40.6% of that during 0-25 days and 36-60 days. Metabolomic results identified 61 significantly different metabolites (SDMs), of which, the most significantly increased and decreased SDMs after weaning were ectoine and taurocholate, respectively, indicating the occurrence of inflammation. Metagenomic analysis identified 30 significantly different microbes before and after weaning. Bacteria related to decreasing intestinal inflammation, such as Megasphaera, Alistipes and Bifidobacterium, were enriched before weaning. While bacteria related to infection such as Chlamydia, Clostridium, Clostridioides, and Blautia were enriched after weaning. The carbohydrate enzymes CBM91, CBM13, GH51_1, and GH94 increase after weaning, which may contribute to the digestion of complex plant fibers. Furthermore, we found the composition of antibiotic resistance genes (ARGs) changed during weaning. Transcriptomic analysis identified 147 significantly differentially expressed genes (DEGs). The upregulated genes after weaning were enriched in immune response categories, whereas downregulated genes were enriched in protein degradation. Combining multi-omics data, we identified significant positive correlations between gene MZB1, genera Alistipes and metabolite stachydrine, which involve anti-inflammatory functions. The reduced abundance of bacteria Dialister after weaning had strong correlations with the decreased 2-AGPE metabolite and the downregulated expression of RHBDF1 gene. Altogether, the multi-omics study reflects dietary changes and gut inflammation during weaning, highlighting complex interactions between gut microbes, host genes and metabolites."PMID:39723142 | PMC:PMC11668797 | DOI:10.3389/fmicb.2024.1482925

Front Microbiol. 2024 Dec 11;15:1498540. doi: 10.3389/fmicb.2024.1498540. eCollection 2024.ABSTRACTINTRODUCTION: Hyperuricemia (HUA) refers to the presence of excess uric acid (UA) in the blood, which increases the risk of chronic kidney disease and gout. Probiotics have the potential to alleviate HUA.METHODS: This study established a hyperuricemia model using Caenorhabditis elegans (C. elegans), and studied the anti-hyperuricemia activity and potential mechanisms of Weizmannella coagulans BC99 (W. coagulans) at different concentrations (107 CFU/mL BC99, 108 CFU/mL BC99). Subsequently, we utilized UPLC-Q-TOF/MS to investigate the impact of BC99 on endogenous metabolites in C. elegans and identified pathways and biomarkers through differential metabolomics analysis.RESULTS: The results of this study showed that BC99 treatment significantly reduced the expression of P151.2 and T22F3.3 (p < 0.05), reduced the levels of UA and xanthine oxidase (XOD) in nematodes (p < 0.05), while extending their lifespan and movement ability (p < 0.05). Mechanistically, BC99 activates the transcription factors DAF-16 and SKN-1, thereby inducing the expression of stress response genes, enhancing the activity of antioxidant enzymes and tolerance to heat stress in the body, and reducing the production of ROS (p < 0.001). This effect was most significant in the H-BC99 group. Furthermore, non-targeted metabolomics indicated that BC99 predominantly regulated pathways associated with amino acid metabolism (Carnosine), glycerophospholipid metabolism, and purine metabolism.DISCUSSION: These results underscore BC99 as an effective and economical adjunct therapeutic agent for hyperuricemia, providing a scientific basis for further development and application.PMID:39723130 | PMC:PMC11668962 | DOI:10.3389/fmicb.2024.1498540

JIMD Rep. 2024 Dec 22;66(1):e12455. doi: 10.1002/jmd2.12455. eCollection 2025 Jan.ABSTRACTBACKGROUND: Inherited metabolic diseases (IMDs) may have considerable implications for patients and their families. Despite their individual rarity, covering a spectrum of over 1800 distinct diseases, the diseases collectively exert a significant impact, with often lifelong disabilities. The United for Metabolic Diseases consortium was established to catalyze research with translation into the best possible care.AIM: To generate a translational knowledge agenda, which identifies and prioritizes research questions, directly relevant to patient care or for IMD patients and their families.METHODS AND RESULTS: Following a process established by the Knowledge Institute of the Dutch Association of Medical Specialists, we generated a comprehensive translational knowledge agenda for IMDs. A multidisciplinary steering committee, composed of 12 diverse metabolic experts collected research questions through an online questionnaire using snowballing. The 462 proposed questions were categorized and prioritized during a meeting attended by 22 representatives of all stakeholder groups. The resulting top 10 research questions cover multiple themes, i.e. prediction of disease progression, development of novel tools, mechanistic insights, improved diagnostics, therapeutic integration of multi-omics techniques, assessment of impact on daily life, expanding treatment avenues, optimal study designs, effect of lifestyle interventions, and data utilization using FAIR principles.DISCUSSION: This collective endeavor reflects the collaborative spirit needed for rare disease research. This knowledge agenda will guide funding directions and applications but will also boost interdisciplinary collaboration to push the field of IMDs research forward in a renewed UMD consortium. Patient engagement, transparency, and a comprehensive approach make this knowledge agenda a pivotal step toward addressing the pressing research needs and priorities in this domain.PMID:39723120 | PMC:PMC11667762 | DOI:10.1002/jmd2.12455

Food Sci Nutr. 2024 Nov 22;12(12):10666-10679. doi: 10.1002/fsn3.4561. eCollection 2024 Dec.ABSTRACTThis study aimed to investigate the effects of short-term exposure of Bisphenol A (BPA) on the growth and lactation performance, blood parameters, and milk composition of lactating rabbits and explore its potential molecular mechanisms. Eight lactating rabbits with similar body weight were selected and randomly divided into the experimental group (BPA) and the control group (Ctrl). The group BPA was orally administered 80 mg/kg/day BPA on the 15th day postpartum, while the group Ctrl received a corresponding volume of vehicle. Blood and milk samples were collected after 7 days treatment. The results showed that short-term ingestion of BPA did not obviously alter the body weight, feed intake, or milk yield of the lactating rabbits. ELISA assays indicated that BPA did not significantly affect the plasma levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), creatinine (CRE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA), and urea. Utilizing untargeted metabolomics, we first depicted the metabolomic profile of rabbit milk, and identified 277 differential metabolites (DMs), with 141 DMs upregulated (e.g., BPA, and its metabolites including Cetirizine N-oxide) and 136 DMs downregulated (e.g., Oleamide, Tiglic acid, PC O-38:4) in the group BPA. KEGG analysis revealed that the DMs were mainly enriched in pathways comprising fatty acid metabolism, fatty acid degradation, and phosphatidylinositol signaling system, emphasizing the effect of BPA on milk fat metabolism. Hence, we established the BPA-induced MAC-T model, and the results showed that BPA significantly reduced cell viability and impacted lipid synthesis, as evidenced by reduced lipid droplets (BODIPY and Oil Red O staining) and decreased expression of genes related to lipid synthesis (e.g., PPARγ, ACACA, LPL). In summary, we first drew the metabolomic profile of rabbit milk and confirmed that short-term BPA exposure impacted mammary lipid synthesis, thereby reducing the milk quality of lactating rabbits and providing fundamental data for resolving the toxicological mechanisms of BPA on mammal lactation.PMID:39723079 | PMC:PMC11666964 | DOI:10.1002/fsn3.4561

Front Chem. 2024 Dec 11;12:1518110. doi: 10.3389/fchem.2024.1518110. eCollection 2024.ABSTRACTBACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) influenced by multiple factors. Berberine, an isoquinoline alkaloid derived from the root and bark of Coptis chinensis Franch., has shown promise in managing UC, but its underlying mechanisms remain unclear.METHODS: To elucidate the relationship between berberine, ulcerative colitis (UC), and the organism's metabolome, we established a dextran sulfate sodium (DSS)-induced UC model in rats. Colonic tissue was collected for histopathological examination, while plasma samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with dynamic Multiple Reaction Monitoring (dMRM). This approach, characterized by its short analysis time of 20 min per sample, excellent reproducibility, and straightforward data processing, allowed for the comprehensive detection of a wide array of metabolites, including amino acids, lipids, and organic acids, many of which are implicated in the pathophysiology of UC.RESULTS: Our results showed that berberine modulated the metabolic disturbances of 33 compounds in the plasma of UC rats, primarily including amino acids, pyrimidines, organic phosphoric acids, fatty acyls, and organonitrogen compounds. These altered metabolites were associated with various pathways, such as amino acid metabolism, glutathione metabolism, nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism, pyrimidine metabolism, glyoxylate and dicarboxylate metabolism, and the citrate cycle (TCA cycle). Notably, 3-hydroxyproline, homocysteic acid, L-threonine, L-lysine, carbamoyl phosphate, O-phosphoethanolamine, taurine, leucine, and phosphorylcholine exhibited significant differences between the Treatment and Model groups, with levels reverting to those of the Control group (p < 0.001). These findings suggested that these compounds may serve as potential plasma biomarkers for UC.CONCLUSION: This study provided valuable insights into the mechanism by which berberine exerted its therapeutic effects on UC through metabolomics. Our results highlighted berberine's potential to modulate key metabolic pathways and restore the levels of several metabolites, suggesting its utility as a therapeutic agent for UC. These findings underscored the importance of metabolomics in understanding the pathophysiology and treatment of UC.PMID:39722837 | PMC:PMC11668600 | DOI:10.3389/fchem.2024.1518110

Drug Des Devel Ther. 2024 Dec 21;18:6221-6222. doi: 10.2147/DDDT.S502748. eCollection 2024.NO ABSTRACTPMID:39722681 | PMC:PMC11669341 | DOI:10.2147/DDDT.S502748

Drug Des Devel Ther. 2024 Dec 21;18:6223-6241. doi: 10.2147/DDDT.S486286. eCollection 2024.ABSTRACTINTRODUCTION: Acute kidney injury (AKI) is linked to high rates of mortality and morbidity worldwide thereby posing a major public health problem. Evidences suggest that ferroptosis is the primary cause of AKI, while inhibition of monoamine oxidase A(MAOA) and 5-hydroxytryptamine were recognized as the defender of ferroptosis. Curcumin (Cur) is a natural polyphenol and the main bioactive compound of Curcuma longa, which has been found nephroprotection in AKI. However, the potential mechanism of Cur in alleviating AKI ferroptosis remains unknown.OBJECTIVE: This study aims to investigate the effects of Cur on AKI ferroptosis.METHODS: Folic acid (FA)-induced AKI mouse model and erastin/(rsl-3)-induced HK-2 model were constructed to assess the renoprotection of Cur. The nuclear magnetic resonance (NMR)-based metabolomics coupled network pharmacology approach was used to explore the metabolic regulation and potential targets of Cur. Molecular docking and enzyme activity assay was carried out to evaluate the effects of Cur on MAOA.RESULTS: Our results showed that in vivo Cur preserved renal functions in AKI mice by lowering levels of serum creatinine, blood urea nitrogen, while in vitro ameliorated the cell viability of HK-2 cells damaged by ferroptosis. Mechanistic studies indicated that Cur protected AKI against ferroptosis via inhibition of MAOA thereby regulating 5-hydroxy-L-tryptophan metabolism.CONCLUSION: Our study for the first time clarified that Cur might acts as a MAOA inhibitor and alleviates ferroptosis in AKI mice, laying a scientific foundation for new insights of clinical therapy on AKI.PMID:39722679 | PMC:PMC11669278 | DOI:10.2147/DDDT.S486286

Se Pu. 2025 Jan;43(1):50-59. doi: 10.3724/SP.J.1123.2024.05028.ABSTRACTArsenic is a ubiquitous environmental toxin that can affect normal physiological processes. Although the health impacts of arsenic have been investigated, its influence on hepatic metabolism in obese pregnant women and the underlying mechanisms remain unclear. Multi-omics analysis, including metabolomics and proteomics, can improve the understanding of arsenic-induced hepatotoxicity in obese pregnant women. This study aimed to investigate the adverse effects of gestational arsenic exposure on hepatic metabolism in high-fat-diet-induced obese pregnant mice. Following arsenic exposure during pregnancy, the liver tissue was evaluated comprehensively using metabolomics and proteomics techniques combined with pathological and biochemical analyses. Arsenic exposure not only significantly increased lipid accumulation in the livers of obese pregnant mice but also elevated inflammatory factors and oxidative stress markers. Specifically, histopathological examination revealed more steatosis, inflammatory cell infiltration, and hepatocyte ballooning in the livers of arsenic-exposed mice than in those of controls. These changes indicate that arsenic exposure exacerbates hepatic lipid accumulation and induces liver damage in the context of obesity. Metabolomic analysis provided further insight into the metabolic-level disruption caused by arsenic exposure. Significant changes were observed in lipid metabolism pathways, particularly the arachidonic acid metabolism pathway. As arachidonic acid and its metabolites play important roles in inflammation and oxidative stress, this pathway may be critical in arsenic-induced hepatotoxicity. Additionally, proteomic analysis showed differences in the expression levels of several key proteins involved in lipid synthesis, oxidative stress, and inflammatory response. Notably, oxidative-stress-related proteins, including glutathione peroxidase 4 (GPX4), were upregulated, suggesting an increased oxidative burden. In summary, there are complex interaction mechanisms among arsenic exposure, inflammatory response, and related lipid metabolism. The integration of metabolomics and proteomics aided in clarifying the molecular alterations induced by arsenic. The results show that arsenic exposure significantly affects hepatic lipid metabolism in obese pregnant mice through multiple metabolic pathways and protein regulatory mechanisms. In addition to providing new insights into the relationship between arsenic exposure and obesity as well as related metabolic diseases, this study can act as a reference for environmental health risk assessment and the formulation of public health policies. This enhanced understanding of the adverse effects of arsenic on hepatic metabolism will contribute to the development of strategies for mitigating the health risks associated with environmental toxins, particularly for vulnerable groups such as obese pregnant women.PMID:39722621 | DOI:10.3724/SP.J.1123.2024.05028

Se Pu. 2025 Jan;43(1):33-42. doi: 10.3724/SP.J.1123.2024.03014.ABSTRACTEmerging contaminants and their transformation products are widely distributed in the environment. These pollutants carry unknown risks owing to their persistence, migration, and toxicity. The wide variety and complex structures of these substances render them difficult to identify using only target analysis. Suspect screening analysis can identify more substances than target analysis in a single run. However, this analysis method is based on limited data and cannot meet the growing demand for compound identification, especially for emerging contaminants and their transformation products with unknown information. The development of high-resolution mass spectrometry technology has promoted the applications of nontarget analysis in the environmental field, especially for identifying unknown transformation products. At present, the challenges of nontarget analysis include the difficulty of finding compounds of interest and their transformation products from complex data. Molecular networking calculates the similarity between mass spectra based on an improved cosine similarity algorithm. This method can cluster molecular families with similar structures, achieve visualization and a collection of massive mass spectral datasets, and promote the annotation of pollutants through networks and communities. Molecular networking can globally organize and systematically interpret complex tandem mass spectral datasets, providing a new direction for nontarget analysis. This technology was first used in proteomics and gradually introduced into metabolomics for the discovery of new natural products. Recently, it has been introduced into the environmental field for the study of various man-made chemicals, particularly for the discovery of emerging contaminants and their transformation products. In this paper, we introduce a molecular networking analysis method based on high-resolution tandem mass spectrometry and describe its applications in the nontargeted screening of emerging contaminants, focusing on the technical principles, workflow, application status, and future development prospects. This paper discusses the applications of molecular networking technology in the detection of emerging contaminants and their transformation products such as drugs, perfluorinated compounds, and disinfection byproducts. Molecular networking technology is widely applicable to the screening of emerging contaminants in various environmental media, revealing the full range of pollutants in the environment and promoting studies on the environmental behavior and toxicological properties of these compounds.PMID:39722619 | DOI:10.3724/SP.J.1123.2024.03014

Gut Microbes. 2025 Dec;17(1):2446374. doi: 10.1080/19490976.2024.2446374. Epub 2024 Dec 26.ABSTRACTGut microbial metabolism of L-carnitine, which leads to the production of detrimental trimethylamine N-oxide (TMAO), offers a plausible link between red meat consumption and cardiovascular risks. Several microbial genes, including cntA/B, the cai operon, and the recently identified gbu gene cluster, have been implicated in the conversion of dietary L-carnitine into TMA(O). However, the key microbial genes and associated gut microbes involved in this pathway have not been fully explored. Utilizing the oral carnitine challenge test (OCCT), which specifically measures TMAO production from L-carnitine intake and identifies TMAO producer phenotypes, we compared the abundance of microbial genes between low- and high-TMAO producers across three independent cohorts. Our findings consistently revealed that the gbu gene cluster, rather than cntA/B or the cai operon, was significantly enriched in high-TMAO producers. We further analyzed 292 paired multi-omic datasets from OCCT and shotgun metagenomic sequencing, which demonstrated a significant positive correlation between the abundance of fecal gbu genes and L-carnitine-induced TMAO production, with gbuB showing the strongest correlation. Interestingly, these fecal gbu genes were found to increase with L-carnitine supplementation and decrease with a plant-based diet. Notably, we verified a previously uncultured gbu-containing bacterium, JAGTTR01 sp018223385, as the major contributor to TMA formation in the human gut. We isolated these gbu-containing gut microbes and confirmed their role in TMA/TMAO production using anaerobic incubation and a gnotobiotic mouse model. Using an in-house collection of gbu-containing isolates, we developed a qPCR-based method to quantify fecal gbuB and validated its correlation with L-carnitine-mediated TMAO production as measured by OCCT. Overall, these findings suggest that gbu-containing gut microbes are crucial for TMAO increases following L-carnitine intake and may serve as biomarkers or targets for personalized nutrition.PMID:39722590 | DOI:10.1080/19490976.2024.2446374

Glia. 2024 Dec 25. doi: 10.1002/glia.24646. Online ahead of print.ABSTRACTThe relative ease of generation and proliferation of omics datasets has moved considerably faster than the effective dissemination of these data to the scientific community. Despite advancements in making raw data publicly available, many researchers struggle with data analysis and integration. We propose sharing analyzed data through user-friendly platforms to enhance accessibility. Here, we present a free, online tool, for sharing basic omics data in a searchable and user-friendly format. Importantly, it requires no coding or prior computational knowledge to build-only a data spreadsheet. Overall, this tool facilitates the exploration of transcriptomic, proteomic, and metabolomics data, which is crucial for understanding glial diversity and function. This initiative underscores the importance of accessible molecular data in advancing neuroscience research.PMID:39722526 | DOI:10.1002/glia.24646

Crit Rev Food Sci Nutr. 2025;65(2):406-428. doi: 10.1080/10408398.2023.2274949. Epub 2023 Nov 1.ABSTRACTAmadori compounds (ACs) are key intermediates of the Maillard reaction, and found in various thermally processed foods. Simultaneous analysis of multiple ACs is challenging due to the complex amino acid and carbohydrate compositions, and the different food matrices. Most studies focus on the effects of ACs on food flavor and related sensory properties, but not their biological functions. However, increasing evidence shows that ACs possess various beneficial effects on human health, thus a comprehensive review on the various biological activities is warranted. In this review, we summarized the composition and content of ACs in different foods, their formation and degradation reactions, and discussed the latest advances in analytical methods of ACs and their biological functions related to human health. Limitations and research gaps were identified and future perspectives on ACs research were proposed. This review points to the needs of systematic and comprehensive in vitro and in vivo studies on human health related biological functions of ACs and their mechanisms of action, particularly the synergistic effects with other food components and drugs, and roles in intestinal health and metabolic syndrome.PMID:39722481 | DOI:10.1080/10408398.2023.2274949

Mol Plant. 2024 Dec 24:S1674-2052(24)00398-8. doi: 10.1016/j.molp.2024.12.014. Online ahead of print.NO ABSTRACTPMID:39722454 | DOI:10.1016/j.molp.2024.12.014

J Ethnopharmacol. 2024 Dec 23:119244. doi: 10.1016/j.jep.2024.119244. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory Bowel Disease (IBD), encompassing Ulcerative Colitis (UC) and Crohn's Disease (CD), stems from a multifaceted interaction of hereditary, immunological, ecological, and microbial elements. Current treatments have limitations, necessitating new therapeutic approaches.AIM OF THE STUDY: This study investigates the safeguarding impacts and fundamental processes of extracts of Gleditsia sinensis Lam. thorn (EGST) in a dextran sulfate sodium (DSS)-induced colitis model in mice.MATERIALS AND METHODS: A total of 180g of dried EGST were prepared, and untargeted metabolomic profiling using high-resolution liquid chromatography electrospray ionization orbitrap mass spectrometry (HR-LC-ESI-Orbitrap-MS) identified 930 compounds. UC model mice were administered 3% DSS for 7 d, followed by EGST treatment. The analysis encompassed physiological and pathological evaluations, serum cytokine ELISA, gut microbiota (GM) metagenomic sequencing, GC-MS metabolomics, mRNA sequencing, and Western Blot.RESULTS: EGST markedly mitigated colitis symptoms, evidenced by reduced weight loss, lower DAI scores, and less colon shortening. It also decreased levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) while boosting IL-10. Histological examination revealed diminished tissue damage, restoration of crypts, and reduced inflammation, with barrier integrity maintained via upregulation of occludin and ZO-1. Metagenomic sequencing demonstrated that EGST modulated the GM, enhancing the levels of Firmicutes and Bacteroidetes while reducing the levels of Proteobacteria and Verrucomicrobia. Metabolomic analysis indicated that EGST influenced critical pathways, including those involving D-amino acids, glutathione, cysteine, and methionine metabolism. Furthermore, mRNA sequencing identified 2,625 differentially expressed genes (DEGs), comprising 1,729 with increased and 896 with decreased expression, and highlighted EGST's impact on the PPARγ/AMPK/NF-κB pathway.CONCLUSION: Overall, EGST mitigates DSS-induced colitis through modulation of GM, metabolic profiles, and gene expression, suggesting its promise as a naturally derived treatment for colitis.PMID:39722326 | DOI:10.1016/j.jep.2024.119244

Life Sci. 2024 Dec 23:123332. doi: 10.1016/j.lfs.2024.123332. Online ahead of print.ABSTRACTBACKGROUND AND PURPOSE: Sepsis is a condition capable of causing systemic inflammation and metabolic reprogramming. Previous studies have shown that sinomenine (SIN) can mitigate sepsis by reducing inflammation, while the effect on metabolic reprogramming is unclear. The aim of this study is to investigate the function of SIN in metabolic reprogramming in sepsis.EXPERIMENTAL APPROACH: Differential metabolites in lung tissue and serum were analyzed by 1H Nuclear Magnetic Resonance (1H NMR) and metabolomics were used to compare metabolic changes in septic mice. Nicotinic acetylcholine receptors alpha7 subunit (CHRNA7)-Knockdown (KD) mice and other techniques, were used to detect the expression of markers of several metabolic pathways.KEY RESULTS: Metabolomics studies showed that SIN could affect energy metabolism, particularly glucose metabolism, and this effect may be related to the activation of CHRNA7. Further studies showed that SIN could inhibit aerobic glycolysis, promote glutamine anaplerosis, reduce pentose phosphate pathway flux and ultimately mediate metabolic reprogramming.CONCLUSION AND IMPLICATIONS: SIN restores glycolysis and glutamine anaplerosis by interacting with CHRNA7, thereby mediating metabolic reprogramming and mitigating sepsis. These findings shed light on the mechanism of SIN in attenuating sepsis from a metabolic perspective.PMID:39722318 | DOI:10.1016/j.lfs.2024.123332

Biol Psychiatry. 2025 Feb 1;97(3):210-211. doi: 10.1016/j.biopsych.2024.11.004.NO ABSTRACTPMID:39722255 | DOI:10.1016/j.biopsych.2024.11.004

BMC Plant Biol. 2024 Dec 26;24(1):1247. doi: 10.1186/s12870-024-05944-2.ABSTRACTBACKGROUND: Saffron (Crocus sativus L.) is a perennial, bulbous flower whose stigma is one of the most valuable spices, herbal medicines, and dyes. Light is an essential environmental regulator of plant growth, development, and metabolism. With the popularization of customized light-emitting diode (LED) light sources in facility agriculture, accurate light control has become essential for regulating crop yield and quality. In this study, white, red, and blue LED lights were applied to extend the photoperiod at the start and end of the day during the indoor stage of saffron cultivation. We investigated saffron growth and flowering using non-target metabolomic and transcriptome analyses to determine the flux and accumulation of metabolites from the stigma under different light treatments.RESULTS: The results revealed that supplemental red and white lights both promoted dry mass accumulation in the stigma, with the optimal appearance achieved using white light. Supplemental white light promoted saffron flowering, whereas supplemental blue light delayed it. Supplemental blue light promoted crocin-1 and crocin-3 accumulation, whereas supplemental red light promoted crocin-2 accumulation. Expression analysis of key genes and their correlations with crocin-related metabolites may provide useful information for screening functional genes involved in crocin synthesis.CONCLUSIONS: This study provides useful information for future application of LED light to improve the planting technology, quality, and yield of saffron, and reveals underlying molecular information for the further research.PMID:39722040 | DOI:10.1186/s12870-024-05944-2

Water Res. 2024 Dec 21;273:123033. doi: 10.1016/j.watres.2024.123033. Online ahead of print.ABSTRACTHigh temperature (HT) shock is one of environmental stressors suppressing microalgal activities in microalgal wastewater bioremediation system. However, its inhibition mechanism and how to alleviate such suppression remain inadequately understood. This study confirmed a transient ferroptosis as a novel form of programmed cell death in a wastewater-indigenous Chlorella sp., responding to a 30-minute HT (50 °C) exposure, through the systematically physiological, metabolomic and transcriptomic analysis. Specifically, the HT-induced ferroptosis could be supported by both the growth and physiological indicators. These include the suppressed growth (76.05 %), suppressed nutrient removals (NH4+-N by 76.22 %, PO43--P by 64.15 %), accumulated intracellular Fe3+ concentrations (7.75-fold), enhanced oxidative stress (e.g., increased levels of reactive oxygen species (159.97 %)), activated antioxidant defense system (e.g., increased activities of superoxide dismutase (24.83 %) and catalase (5.03-fold)), and obvious membrane damage (e.g., increased levels of malondialdehyde (1.67-fold)). Further metabolomic analysis indicated that such HT-induced ferroptosis was also largely related to the significant alternations of lipid remodeling in three aspects: varied abundance of certain lipids specific to chloroplast membrane or mitochondria, accumulation of certain lipids with lower unsaturation, and formation of lipid peroxides disrupting membrane integrity. Moreover, the key genes involved in ferroptosis correspondingly responded, especially those associated with lipid metabolism (e.g., ACSL), antioxidant defense system (e.g., GSS, GPX and GSR), mitochondrial normal functioning (e.g., SEL1L), autophagy regulation (e.g., ATG9, ATG11, ATG13) and protein folding (e.g., HSPA5, HSPA1s, HSP90B). In addition, the supplementation of the typical ferroptosis inhibitor Ferrostatin-1 effectively mitigated lipid peroxide accumulation and suppressed the onset of ferroptosis, accelerating subsequent recovery of NH4+-N removal by 60.66 %. These findings update current understandings of microalgal ferroptosis-like inhibition, offering Ferrostatin-1 supplementation as a potential strategy for system resistance to heat stress in microalgae-based bioremediation system.PMID:39721506 | DOI:10.1016/j.watres.2024.123033