PubMed

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

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

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

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

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

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

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

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

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

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