PubMed
Sinomenine modulates the metabolic reprogramming induced by sepsis via CHRNA7
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
Antenatal Depression and Metabolomics: A Step to Understand Transgenerational Mechanisms in Mental Health
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
Effects of supplementary light treatment on saffron: integrated physiological, metabolomic, and transcriptome analyses
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
Ferrostatin supplementation improves microalgal activities and nutrient removal in wastewater under high temperature shock: From ferroptosis-like inhibition to enhanced oxidation resistance
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
Multi-omic investigation identifies key antifungal biochemistry during fermentation of a Streptomyces biological control agent
Microbiol Res. 2024 Dec 18;292:128032. doi: 10.1016/j.micres.2024.128032. Online ahead of print.ABSTRACTThe use of multi-omic approaches has significantly advanced the exploration of microbial traits, leading to the discovery of new bioactive compounds and their mechanisms of action. Streptomyces sp. MH71 is known for its antifungal properties with potential for use in crop protection. Using genomic, transcriptomic, and metabolomic analyses, the antifungal metabolic capacity of Streptomyces sp. MH71 was investigated. After 96 hours of liquid fermentation, cell-free spent media showed inhibitory activity against the fungal phytopathogen Verticillium dahliae, with the lowest IC50 value being 0.11 % (v/v) after 144 h. Through whole-genome sequencing, we obtained a near-complete genome of 11 Mb with a G+C content of 71 % for Streptomyces sp. MH71. Genome mining identified 50 putative biosynthetic gene clusters, six of which produced known antimicrobial compounds. To link antifungal activity with candidate biosynthetic pathways, a transcriptomic approach was applied to understand antifungal induction in MH71 cells during the observed increase in antifungal activity. This approach revealed 2774 genes that exhibited differential expression, with significant upregulation of genes involved in biosynthesis of secondary metabolites during the stationary growth phase. Metabolomic analyses using LC-MS and GC-MS of secreted compounds identified a cocktail of potent antifungal metabolites, including volatiles with antifungal activity. By combining genome mining, bioactivity data, transcriptomics, and metabolomics, we describe in detail the gene expression and metabolite products driving antifungal activity during microbial fermentation.PMID:39721340 | DOI:10.1016/j.micres.2024.128032
Exploring variances in meat quality between Qingyuan partridge chicken and Cobb broiler: Insights from combined multi-omics analysis
Poult Sci. 2024 Dec 12;104(2):104666. doi: 10.1016/j.psj.2024.104666. Online ahead of print.ABSTRACTPreviously, animal breeding prioritized enhancing key economic traits to improve production efficiency, leading to a gradual difference in meat quality. However, the genetic factors influencing meat quality remain unclear. To identify key genetic pathways contributing to meat quality, native Chinese yellow-feathered chicken (Qingyuan Partridge Chicken, QPC; female, n=10), and commercial chicken broiler (Cobb broiler, CB; female, n=10) were used for meat quality assessment through metabolomics, proteomics, and phosphoproteomics sequencing. The results show that QPC had lower pH (93.12%), shear force (81.46%), cooking loss (69.29%), moisture content (93.24%) and muscle fiber area (46.04%), but higher meat color values (a*(163.65%) and b*(250.27%)), drip loss (146.32%), and intramuscular fat content (382.01%) than CB (p < 0.05). Metabolomic, proteomic, and phosphoproteomic analyses were jointly conducted, revealing significant differences in energy metabolism strategies. Higher glycolytic enzyme activity was observed in QPC (ENO1, GAPDH, GPI, PFKM, PKM, and TPI1, p < 0.05), while more energetic phosphate compounds were stored in CB. CB had higher Na+/K+ Pump protein abundance (SCN4A, LOC107051305, ATP1B4, ATP12A, ATP1A1, and ATP1A2, p < 0.05) and phosphorylation (ATP1A2-Ser662, p < 0.05) and Ca2+ channel protein abundance (ATP2B4, SRL, CACNB1, CACNA1S, CACNA2D1, CAMK2G, LOC107050717 and TNNC2, p < 0.05) than QPC. In QPC, CAMKII autophosphorylation activated downstream protein and increased Ca2+. These results suggest CB is more contractile than QPC, contributing to meat quality between CB and QPC.PMID:39721276 | DOI:10.1016/j.psj.2024.104666
Microbiome and metabolome reveal beneficial effects of baicalin on broiler growth performance and intestinal health
Poult Sci. 2024 Dec 16;104(2):104678. doi: 10.1016/j.psj.2024.104678. Online ahead of print.ABSTRACTNormal function and health of the intestinal tract were necessary for the growth and development of broilers. Baicalin (BA) possessed a variety of biological activities. The objective of this study was to examine the impact of BA on the growth performance, intestinal barrier function, intestinal microbiota, and mucosal metabolism in broilers. A total of 720 21-day-old broilers were randomly allocated into 3 groups and fed with either basal diet (Con group) or basal diet supplemented with 6 or 12 mg/kg baicalin (BA6 and BA12 groups) for a continuous feeding period of 40 days. Results showed that BA had a trend towards improving (P = 0.086) the 60-day body weight of broilers, and the BA12 group exhibited significantly higher (P < 0.05) average daily gain from day 39 to 60 compared to the Con group. Additionally, in the BA12 group, the ratio of villus height to crypt depth and the expression levels of tight junction protein-related genes significantly increased (P < 0.05), while intestinal permeability significantly decreased (P < 0.05). Supplementation with 12 mg/kg BA significantly enhanced antioxidant capacity, promoted (P < 0.05) crypt proliferation, increased (P < 0.05) immunoglobulin levels, upregulated (P < 0.05) IL-2 and IL-8 mRNA levels, and downregulated (P < 0.05) IL-4 and TGF-β2 mRNA levels. Metabolomics analysis revealed that BA improved the metabolic characteristics of intestinal mucosa, significantly upregulating pathways associated with ascorbate and aldarate metabolism, glyoxylate and dicarboxylate metabolism, phosphatidylinositol signaling system, alpha-linolenic acid metabolism, and galactose metabolism. 16S rRNA sequencing results indicated that BA increased the richness of intestinal microbiota community and the relative abundance of Actinobacteria phylum, while reducing the relative abundance of contains mobile elements, potentially pathogenic, and facultatively anaerobic. Overall, 12 mg/kg BA improved intestinal health by modulating intestinal barrier function, antioxidant capacity, immunity, intestinal microbiota, and intestinal mucosal metabolism levels, ultimately enhancing broiler growth performance.PMID:39721274 | DOI:10.1016/j.psj.2024.104678
Microbial metabolism of host-derived antioxidants
Curr Opin Chem Biol. 2024 Dec 24;84:102565. doi: 10.1016/j.cbpa.2024.102565. Online ahead of print.ABSTRACTHumans are exposed to a wide variety of small molecules with antioxidant properties that are poorly metabolized by mammalian cells. However, gastrointestinal microbes encode enzymes that convert these redox-active molecules into nutrient sources and electron acceptors to support bacterial growth in the gut. Here, we describe recent studies highlighting how microbial metabolism of host-derived antioxidants modulates interspecies interactions and provide an overview of the interdisciplinary approaches being used to map these metabolic pathways in vivo. Uncovering microbe-driven biotransformations of redox-active small molecules could create new opportunities to improve human health by modulating redox reactions at the host-microbe interface.PMID:39721219 | DOI:10.1016/j.cbpa.2024.102565
Enrichment of rice endosperm with anthocyanins by endosperm-specific expression of rice endogenous genes
Plant Physiol Biochem. 2024 Dec 18;219:109428. doi: 10.1016/j.plaphy.2024.109428. Online ahead of print.ABSTRACTA diet rich in anthocyanins can benefit human health against a broad spectrum of human diseases due to the high antioxidant activities of anthocyanins. Enrichment of anthocyanins in the starchy endosperm of rice is an effective solution to provide nutritional food in human diets. However, previous attempts failed to engineer anthocyanin biosynthesis in the rice endosperm by transgenic expression of rice endogenous genes. In this study, four rice endogenous genes, OsDFR (encoding dihydroflavonol 4-reductase), OsRb (encoding a bHLH family transcription factor), OsC1 (encoding an R2R3-MYB-type transcription factor) and OsPAC1 (encoding a WD40 class protein), were employed to rebuild the anthocyanin biosynthesis pathway in the rice endosperm. Endosperm-specific expression of OsDFR-OsRb-OsC1 (DRC) or OsDFR-OsPAC1-OsRb-OsC1 (DPRC) resulted in transgenic rice germplasm with dark purple grains. The expression of endogenous anthocyanin biosynthesis-related genes was significantly upregulated in the transgenic lines. Metabolomics analysis revealed a substantial increase in flavonoids flux, including 12 anthocyanins, in the polished grains of these transgenic lines. Our findings demonstrated that ectopic expressing a minimal set of three rice endogenous genes enabled de novo anthocyanin biosynthesis in the rice endosperm. This study contributes valuable insights into the molecular mechanisms underlying rice organ coloration and provides valuable guidance for future anthocyanin biofortification in crops.PMID:39721185 | DOI:10.1016/j.plaphy.2024.109428
Functional genomics of primary congenital glaucoma by pathway analysis and functional characterization of CYP1B1 mutations
Vision Res. 2024 Dec 24;227:108534. doi: 10.1016/j.visres.2024.108534. Online ahead of print.ABSTRACTCYP1B1 is the most common gene implicated in primary congenital glaucoma (PCG) - the most common form of childhood glaucoma. How CYP1B1 mutations cause PCG is not known. Understanding the mechanism of PCG caused by CYP1B1 mutations is crucial for disease management, therapeutics development, and potential prevention. We performed a comprehensive metabolome/reactome analysis of CYP1B1 to enlist CYP1B1-mediated processes in eye development. The identified metabolic events were classified into major pathways. Functional analysis of these metabolic pathways was performed after cloning the CYP1B1 wild-type gene and expressing the wild-type and selected novel mutants (previously reported by our group L24R, F190L, H279D, and G329D) in heterologous hosts. Stability and enzymatic functions were investigated. Structural modeling of the wild-type and the variants was also performed. Reactome analysis revealed a total of 166 metabolic processes which could be classified into four major pathways including estradiol metabolism, retinoic acid metabolism, arachidonic acid metabolism, and melatonin metabolism. Stability assay revealed rapid denaturing of mutant proteins compared to wild-type. Enzymatic assays showed functional deficit in mutant proteins in metabolizing estradiol, retinoids, arachidonate, and melatonin. Modeling revealed that the examined mutations induced structural changes likely causative in functional loss in CYB1B1 as observed in enzymatic assays. Hence, mutations in the CYP1B1 gene are associated with a functional deficit in critical pathways of eye development. These findings implicate the potential contributions of altered metabolic regulations of estradiol, retinoids, arachidonate and melatonin to the pathogenesis of PCG during the processes of the formation of ocular structures and function.PMID:39721180 | DOI:10.1016/j.visres.2024.108534
A Systematic Review of the Molecular Mechanisms Involved in the Association Between PCOS and Endometrial and Ovarian Cancers
J Cell Mol Med. 2024 Dec;28(24):e70312. doi: 10.1111/jcmm.70312.ABSTRACTPolycystic ovary syndrome (PCOS), a major cause of female infertility, affects 4%-20% of reproductive-age women. Metabolic and hormonal alterations are key features of PCOS, potentially raising the risk of endometrial (EC) and ovarian (OVCA) cancers. This systematic review aims to summarise the proposed molecular mechanisms involved in the association between PCOS and EC or OVCA. This is achieved by conducting a thorough literature review and utilising specific search terms to identify all relevant studies published in English from 2010 to December 2022. PRISMA was followed, and the protocol was registered on PROSPERO (CRD42022375461). The QUADAS-2 tool and Review Manager Software were employed to evaluate study quality and risk of bias respectively. Forty-five eligible studies were selected with molecular signatures based on genomic, transcriptomic, metabolomic, proteomic and epigenetic analyses. Genes and their products deregulated in EC and/or OVCA were identified, including BRCA1, MLH1, NQO1 and ESR1, which were also deregulated in PCOS. Serum levels of IGF1, IGFBP1, SREBP1 and visfatin in women with PCOS were also identified as potential biomarkers of enhanced EC risk. Salusin-β serum levels in individuals with PCOS were identified as a potential biomarker for increased risk of OVCA. Gene signature-based drug repositioning identified several drug candidates: metformin, fenofibrate, fatostatin, melatonin, resveratrol and quercetin, some already established and prescribed for PCOS. In conclusion, this study provides a strong basis for further research to confirm the identified molecular signatures and associated causal links for potential therapeutic prevention strategies for EC and OVCA in women with PCOS.PMID:39720923 | DOI:10.1111/jcmm.70312
Immune and physiological responses in <em>Penaeus monodon</em> to ammonia-N stress: a multi-omics approach
Front Immunol. 2024 Dec 10;15:1510887. doi: 10.3389/fimmu.2024.1510887. eCollection 2024.ABSTRACTAmmonia-N stress is a significant environmental factor that adversely affects the health and productivity of aquaculture species. This study investigates the effects of ammonia-N stress on the shrimp Penaeus monodon through a combination of biochemical, histological, transcriptomic, and metabolomic analyses. Shrimp were exposed to ammonia-N stress for 12 and 96 hours, and key markers of oxidative stress, nitrogen metabolism, immune response, and overall health were assessed. The results showed that prolonged ammonia-N exposure causes significant hepatopancreatic damage, including atrophy and deformation. Transcriptomic analysis revealed significant changes in gene expression related to apoptosis, immune response, and key metabolic pathways, with particular emphasis on the disruption of innate immune signaling and defense mechanisms. Metabolomic analysis identified disruptions in nucleotide turnover, antioxidant defenses, and fundamental metabolic processes. These findings suggest that ammonia-N stress induces a multifaceted stress response in shrimp, involving oxidative stress, immune activation, and metabolic disturbances. Understanding these immune-related and metabolic mechanisms provides valuable insights into the molecular responses of crustaceans to environmental stress, laying the foundation for assessing the ecological risk of ammonia-N and identifying potential immunological biomarkers for monitoring and mitigating its adverse effects in aquaculture systems.PMID:39720717 | PMC:PMC11666502 | DOI:10.3389/fimmu.2024.1510887
Novel type 2 diabetes prediction score based on traditional risk factors and circulating metabolites: model derivation and validation in two large cohort studies
EClinicalMedicine. 2024 Dec 6;79:102971. doi: 10.1016/j.eclinm.2024.102971. eCollection 2025 Jan.ABSTRACTBACKGROUND: We aimed to evaluate the incremental predictive value of metabolomic biomarkers for assessing the 10-year risk of type 2 diabetes when added to the clinical Cambridge Diabetes Risk Score (CDRS).METHODS: We utilized 86,232 UK Biobank (UKB) participants (recruited between 13 March 2006 and 1 October 2010) for model derivation and internal validation. Additionally, we included 4383 participants from the German ESTHER cohort (recruited between 1 July 2000 and 30 June 2002 for external validation). Participants were followed up for 10 years to assess the incidence of type 2 diabetes. A total of 249 NMR-derived metabolites were quantified using nuclear magnetic resonance (NMR) spectroscopy. Metabolites were selected with LASSO regression and model performance was evaluated with Harrell's C-index.FINDINGS: 11 metabolomic biomarkers, including glycolysis related metabolites, ketone bodies, amino acids, and lipids, were selected. In internal validation within the UKB, adding these metabolites significantly increased the C-index (95% confidence interval (95% CI)) of the clinical CDRS from 0.815 (0.800, 0.829) to 0.834 (0.820, 0.847) and the continuous net reclassification index (NRI) with 95% CI was 39.8% (34.6%, 45.0%). External validation in the ESTHER cohort showed a comparable statistically significant C-index increase from 0.770 (0.750, 0.791) to 0.798 (0.779, 0.817) and a continuous NRI of 33.8% (26.4%, 41.2%). A concise model with 4 instead of 11 metabolites yielded similar results.INTERPRETATION: Adding 11 metabolites to the clinical CDRS led to a novel type 2 diabetes prediction model, we called UK Biobank Diabetes Risk Score (UKB-DRS), substantially outperformed the clinical CDRS. The concise version with 4 metabolites performed comparably. As only very few clinical information and a blood sample are needed for the UKB-DRS, and as high-throughput NMR metabolomics are becoming increasingly available at low costs, these models have considerable potential for routine clinical application in diabetes risk assessment.FUNDING: The ESTHER study was funded by grants from the Baden-Württemberg state Ministry of Science, Research and Arts (Stuttgart, Germany), the Federal Ministry of Education and Research (Berlin, Germany), the Federal Ministry of Family Affairs, Senior Citizens, Women and Youth (Berlin, Germany), and the Saarland State Ministry of Health, Social Affairs, Women and the Family (Saarbrücken, Germany). The UK Biobank project was established through collaboration between various entities including the Wellcome Trust, the Medical Research Council, Department of Health, Scottish Government, and the Northwest Regional Development Agency. Additional funding was provided by the Welsh Assembly Government, British Heart Foundation, Cancer Research UK, and Diabetes UK, with support from the National Health Service (NHS). The German Diabetes Center is funded by the German Federal Ministry of Health (Berlin, Germany) and the Ministry of Culture and Science of the state North Rhine-Westphalia (Düsseldorf, Germany) and receives additional funding from the German Federal Ministry of Education and Research (BMBF) through the German Center for Diabetes Research (DZD e.V.).PMID:39720612 | PMC:PMC11667638 | DOI:10.1016/j.eclinm.2024.102971
The chicken cecal microbiome alters bile acids and riboflavin metabolism that correlate with intramuscular fat content
Front Microbiol. 2024 Dec 10;15:1494139. doi: 10.3389/fmicb.2024.1494139. eCollection 2024.ABSTRACTIntramuscular fat (IMF) is a key indicator of chicken meat quality and emerging studies have indicated that the gut microbiome plays a key role in animal fat deposition. However, the potential metabolic mechanism of gut microbiota affecting chicken IMF is still unclear. Fifty-one broiler chickens were collected to identify key cecal bacteria and serum metabolites related to chicken IMF and to explore possible metabolic mechanisms. The results showed that the IMF range of breast muscle of Guizhou local chicken was 1.65 to 4.59%. The complexity and stability of ecological network of cecal microbiota in low-IMF chickens were higher than those in high-IMF chickens. Cecal bacteria positively related to IMF were Alistipes, Synergistes and Subdoligranulum, and negatively related to IMF were Eubacterium_brachy_group, unclassified_f_Lachnospiraceae, unclassified_f_Coriobacteriaceae, GCA-900066575, Faecalicoccus, and so on. Bile acids, phosphatidylethanolamine (Pe) 32:1 and other metabolites were enriched in sera of high-IMF chickens versus low-IMF chickens while riboflavin was enriched in sera of low-IMF chickens. Correlation analysis indicated that specific bacteria including Alistipes promote deposition of IMF in chickens via bile acids while the Eubacterium_brachy group, and Coriobacteriaceae promoted formation of riboflavin, glufosinate, C10-dats (tentative), and cilastatin and were not conducive to the IMF deposition.PMID:39720478 | PMC:PMC11667789 | DOI:10.3389/fmicb.2024.1494139
Protein "purity," proteoforms, and the albuminome: critical observations on proteome and systems complexity
Front Cell Dev Biol. 2024 Dec 10;12:1504098. doi: 10.3389/fcell.2024.1504098. eCollection 2024.ABSTRACTINTRODUCTION: The identification of effective, selective biomarkers and therapeutics is dependent on truly deep, comprehensive analysis of proteomes at the proteoform level.METHODS: Bovine serum albumin (BSA) isolated by two different protocols, cold ethanol fractionation and heat shock fractionation, was resolved and identified using Integrative Top-down Proteomics, the tight coupling of two-dimensional gel electrophoresis (2DE) with liquid chromatography and tandem mass spectrometry (LC-MS/MS).RESULTS AND DISCUSSION: Numerous proteoforms were identified in both "purified" samples, across a broad range of isoelectric points and molecular weights. The data highlight several concerns regarding proteome analyses using currently popular analytical approaches and what it means to (i) purify a "protein" if the isolate consists of a wide variety of proteoforms and/or co-purifying species; and (ii) use these preparations as analytical standards or therapeutics. Failure to widely recognize and accept proteome complexity has likely delayed the identification of effective biomarkers and new, more selective drug targets. iTDP is the most logical available analytical technique to effectively provide the necessary critical depth and breadth for complex proteome analyses. Routine analyses at the level of proteoforms will provide the much-needed data for the development and validation of selective biomarkers and drugs, including biologics.PMID:39720005 | PMC:PMC11666697 | DOI:10.3389/fcell.2024.1504098
The metabolomics provides insights into the Pacific abalone (Haliotis discus hannai) response to low temperature stress
Heliyon. 2024 Dec 5;10(23):e40921. doi: 10.1016/j.heliyon.2024.e40921. eCollection 2024 Dec 15.ABSTRACTThe low temperatures in winter, particularly the cold spells in recent years, have posed significant threats to China's abalone aquaculture industry. The low temperature tolerance of cultured abalone has drawn plenty of attention, but the metabolic response of abalone to low-temperature stress remains unclear. In this study, we investigated the metabolomic analysis of Pacific abalone (Haliotis discus hannai) during low-temperature stress. Pacific abalone used two strains of cultured abalone, namely the bottom-sowing cultured strain (DB) and the longline cultured strain (FS), which had different histories of low-temperature acclimation. The results revealed that eight of the top 10 shared differential expression metabolites of the two strains were carbohydrates. According to the results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis, low-temperature stress primarily affected several metabolic pathways. These pathways include ABC transporters, carbohydrate digestion and absorption, starch and sucrose metabolism, lysine degradation, TCA cycle, the phosphotransferase system, the glucagon signaling pathway and pyruvate metabolism. The results suggest that Pacific abalone primarily regulates the expression of carbohydrates to enhance energy supply and anti-freezing protection. These findings are crucial for understanding the mechanism of low-temperature tolerance in Pacific abalone, and can help optimize culture strategies for high-quality abalone aquaculture development.PMID:39719996 | PMC:PMC11666945 | DOI:10.1016/j.heliyon.2024.e40921
Unraveling site-specific seed formation abnormalities in Picea neoveitchii Mast. trees via widely metabolomic and transcriptomic analysis
Front Plant Sci. 2024 Dec 10;15:1495784. doi: 10.3389/fpls.2024.1495784. eCollection 2024.ABSTRACTPicea neoveitchii Mast. is a rare and threatened species of evergreen coniferous tree in China, commonly facing issues such as damaged seeds, abnormal seed growth, and empty seed shells. These abnormalities vary by location; unfortunately, the reasons behind these inconsistencies are completely unknown. This study compared seeds from two 150-year-old trees located in Taibai (Shaanxi province, TB150) and Zhouqu (Gansu province, ZQ150). The results showed significant differences in 43 metabolites and hormone levels, with higher levels of indole-3-acetic acid (IAA), methyl jasmonate (MeJA), and brassinosteroid (BR) in ZQ150, which were associated with more viable seeds. In contrast, TB150 exhibited more damaged seeds and empty seed shells due to higher abscisic acid (ABA) levels. Moreover, to further investigate these inconsistencies, we performed de-novo transcriptomic assembly and functional annotation of unigenes using high-throughput sequencing. A total of 2,355 differentially expressed unigenes were identified between TB150 and ZQ150, with 1,280 upregulated and 1,075 downregulated. Hormone signaling and sugar metabolism-related unigenes were further examined for their role in seed development. ZQ150 increased the number of normal seeds by enhancing endogenous IAA levels and upregulating auxin signaling and sugar metabolism-related genes. Conversely, TB150 showed more empty seed shells, correlated with elevated ABA levels and the activation of ABA signaling genes. We hypothesize that enhanced IAA levels and the upregulation of sugar metabolism and auxin signaling genes promote normal seed development.PMID:39719938 | PMC:PMC11667104 | DOI:10.3389/fpls.2024.1495784
The effects of different hormone combinations on the growth of Panax notoginseng anther callus based on metabolome analysis
Front Plant Sci. 2024 Dec 9;15:1503931. doi: 10.3389/fpls.2024.1503931. eCollection 2024.ABSTRACTPanax notoginseng saponins (PNS), the primary active components of Panax notoginseng (Burk.) F.H.Chen, a traditional and precious Chinese medicinal herb, are mainly derived from the roots of the plant. However, due to the long cultivation period and specific environmental requirements, the PNS supply is often limited. And, callus cultures of P. notoginseng, which grow rapidly, have short production cycles, and can be cultured under controlled conditions, provide a more efficient source for the quick acquisition of saponins. In this study, anthers of P. notoginseng were used as explants, and twelve hormone combinations were tested to induce callus formation. Eight kinds of hormone combinations successfully induced P. notoginseng anther callus. Among these, callus induced by combinations 5 and 7 had the highest saponin content, while those induced by combinations 1 and 3 exhibited the highest relative growth rates. Metabolomic analysis of these four callus types revealed that there were a total of 99 differential metabolites between combinations 5 and 7, 30 between combinations 1 and 3, 123 between combinations 3 and 7, and 116 between combinations 1 and 5. Further analysis showed that the tricarboxylic acid (TCA) cycle metabolites in callus induced by combinations 1 and 3 were significantly upregulated, with corresponding genes showing high expression levels, increased ATP accumulation, and low responses of the auxin response factor PnARF-3 and cytokinin response factor PnCRF-3. The abundance of metabolites in the PNS biosynthesis pathway in callus induced by combinations 5 and 7 increased significantly, with related genes showing high expression levels, increased IPP accumulation, and high responses of PnARF-3 and PnCRF-3. Overexpression of PnARF-3 and PnCRF-3 in callus induced by combination 3 promoted the production of IPP and saponins while reducing ATP production. In conclusion, different hormone combinations affect the distribution of Acetyl-CoA through PnARF-3 and PnCRF-3, resulting in the relative growth rate and saponin of P. notoginseng anther callus differences.PMID:39719933 | PMC:PMC11667561 | DOI:10.3389/fpls.2024.1503931
Type I interferon and mitochondrial dysfunction are associated with dysregulated cytotoxic CD8+ T cell responses in juvenile systemic lupus erythematosus
Clin Exp Immunol. 2024 Dec 25:uxae127. doi: 10.1093/cei/uxae127. Online ahead of print.ABSTRACTJuvenile systemic lupus erythematosus (JSLE) is an autoimmune condition which causes significant morbidity in children and young adults and is more severe in its presentation than adult-onset SLE. While many aspects of immune dysfunction have been studied extensively in adult-onset SLE, there is limited and contradictory evidence of how cytotoxic CD8+ T cells contribute to disease pathogenesis and studies exploring cytotoxicity in JSLE are virtually non-existent. Here, we report that CD8+ T cell cytotoxic capacity is reduced in JSLE versus healthy controls, irrespective of treatment or disease activity. Transcriptomic and serum metabolomic analysis identified that this reduction in cytotoxic CD8+ T cells in JSLE was associated with upregulated type I interferon (IFN) signalling, mitochondrial dysfunction, and metabolic disturbances when compared to controls. Greater interrogation of the influence of these pathways on altered cytotoxic CD8+ T cell function demonstrated that JSLE CD8+ T cells had enlarged mitochondria and enhanced sensitivity to IFN-α leading to selective apoptosis of effector memory (EM) CD8+ T cells, which are enriched for cytotoxic mediator-expressing cells. This process ultimately contributes to the observed reduction in CD8+ T cell cytotoxicity in JSLE, reinforcing the growing evidence that mitochondrial dysfunction is a key pathogenic factor affecting multiple immune cell populations in type I IFN-driven rheumatic diseases.PMID:39719886 | DOI:10.1093/cei/uxae127
Metabolites differences between plaque biofilms of children with different levels of dental caries
Shanghai Kou Qiang Yi Xue. 2024 Oct;33(5):492-499.ABSTRACTPURPOSE: To explore the differences between plaque biofilms of children with different caries activities via metabolomics.METHODS: A case-control study was conducted to investigate the oral health-related behaviors of children in caries-free (CF), low level of early childhood caries(LECC) and high level of early childhood caries (HECC) groups and to collect supragingival plaque biofilms. Untargeted metabolomics was used to detect the compositions of plaque biofilm metabolites in three groups. Orthogonal partial least squares discriminant analysis, volcano plot and heat map were used to analyze the significant differential metabolites between groups with SPSS 26.0 software package.RESULTS: A total of 102 children aged 36 months were included in this study, including 34 children in each group. A total of 660 metabolites belonging to 11 categories were detected. There were statistical differences of 6 metabolites between LECC group and CF group, and 22 metabolites showed statistical differences between HECC group and CF group(P<0.05). Cys Cys Cys Gln, Cys Gln Cys Cys and 5-O-p-coumaroylnigrumin were the common differential metabolites between children with different levels of dental caries.CONCLUSIONS: There are differences in the compositions of plaque biofilms between children with different caries activities and healthy children. Peptides are important differential metabolites within plaque biofilms, also related to oral health.PMID:39719841