PubMed

Pharmacol Res. 2025 Jan 6:107587. doi: 10.1016/j.phrs.2025.107587. Online ahead of print.ABSTRACTPulmonary fibrosis (PF) is a fatal disease with increasing incidence, poor prognosis, and unclear pathogenesis. Our previous research demonstrated the beneficial effects of the natural cyclopeptide Heterophyllin B (HB) in PF. However, the precise mechanism by which HB exerts its effects in PF remains unclear. Our study revealed HB's beneficial effects in alleviating PF symptoms and restoring the intestinal mucosal barrier. Subsequently, the microbiota-dependent antifibrotic efficacy of HB was verified using various delivery routes, antibiotic treatments, and faecal microbiota transplantation. Functionally, 16S rRNA sequencing, untargeted metabolomics, and co-incubation experiments revealed that the antifibrotic efficacy of HB was primarily contingent on the enrichment of Muribaculum intestinale and its metabolite, 3-hydroxybutyric acid. Mechanistically, indoleamine 2,3- dioxygenase 1 (IDO1)-mediated ferroptosis was identified as a pivotal process in initiating PF, and the anti-fibrotic efficacy of HB relies on suppressing IDO1-mediated ferroptosis. Conversely, IDO1 deficiency alleviated the symptoms of bleomycin-induced PF and ferroptosis in mice. Coincidentally, both IDO1 overexpression and ferroptosis were observed in the pulmonary tissue of patients with idiopathic PF. Collectively, this study revealed that HB alleviates PF by eliminating intestinal microecology and metabolism and highlights the feasibility of targeting IDO1 for PF treatment.PMID:39778639 | DOI:10.1016/j.phrs.2025.107587

Pharmacol Res. 2025 Jan 6:107588. doi: 10.1016/j.phrs.2025.107588. Online ahead of print.ABSTRACTAtherosclerosis, a multifactorial progressive inflammatory disease, is the common pathology underlying cardiovascular and cerebrovascular diseases. The macrophage plasticity is involved in the pathogenesis of atherosclerosis. With the advance of metabolomics and epigenetics, metabolites/metabolic and epigenetic modification such as DNA methylation, histone modification and noncoding RNA, play a crucial role in macrophage polarization and the progression of atherosclerosis. Herein, we provide a comprehensive review of the essential role of metabolic and epigenetic regulation, as well as the crosstalk between the two in regulating macrophage polarization in atherosclerosis. We also highlight the potential therapeutic strategies of regulating macrophage polarization via epigenetic and metabolic modifications for atherosclerosis, and offer recommendations to advance our knowledge of the roles of metabolic-epigenetic crosstalk in macrophage polarization in the context of atherosclerosis. Fundamental studies that elucidate the mechanisms by which metabolic and epigenetic regulation of macrophage polarization influence atherosclerosis will pave the way for novel therapeutic approaches.PMID:39778637 | DOI:10.1016/j.phrs.2025.107588

Cell Syst. 2024 Dec 31:101164. doi: 10.1016/j.cels.2024.12.005. Online ahead of print.ABSTRACTWhile proliferating cells optimize their metabolism to produce biomass, the metabolic objectives of cells that perform non-proliferative tasks are unclear. The opposing requirements for optimizing each objective result in a trade-off that forces single cells to prioritize their metabolic needs and optimally allocate limited resources. Here, we present single-cell optimization objective and trade-off inference (SCOOTI), which infers metabolic objectives and trade-offs in biological systems by integrating bulk and single-cell omics data, using metabolic modeling and machine learning. We validated SCOOTI by identifying essential genes from CRISPR-Cas9 screens in embryonic stem cells, and by inferring the metabolic objectives of quiescent cells, during different cell-cycle phases. Applying this to embryonic cell states, we observed a decrease in metabolic entropy upon development. We further uncovered a trade-off between glutathione and biosynthetic precursors in one-cell zygote, two-cell embryo, and blastocyst cells, potentially representing a trade-off between pluripotency and proliferation. A record of this paper's transparent peer review process is included in the supplemental information.PMID:39778581 | DOI:10.1016/j.cels.2024.12.005

Cell Metab. 2025 Jan 7;37(1):3-4. doi: 10.1016/j.cmet.2024.12.001.ABSTRACTDe novo lipogenesis (DNL) is the process whereby cells synthesize fatty acids from acetyl-CoA, contributing to steatosis in fatty liver disease. Two new studies, using genetic mouse models, metabolomics, and pharmacology, identified alternative pathways in DNL and unexpected physiological effects when targeting key enzymes in this pathway.PMID:39778518 | DOI:10.1016/j.cmet.2024.12.001

Plant Physiol Biochem. 2024 Dec 27;220:109441. doi: 10.1016/j.plaphy.2024.109441. Online ahead of print.ABSTRACTAnthocyanin is the primary color-developing component in the pericarp of the passion fruit. Although the pericarp of the passion fruit is anticipated to be a significant source of anthocyanin, however, information regarding anthocyanin biosynthesis in the passion fruit pericarp remains unexplored. Based on metabolomics analysis, a total of five anthocyanins were identified in the purple-skinned passion fruit pericarp, among which three anthocyanins, petunidin-3-O-arabinoside, geranylgeranyl-3,5-O-diglucoside, and petunidin-3-O-rutinoside, play key roles in the coloration of the passion fruit pericarp. Based on proteomics analysis, a total of nine differential proteins are involved in the flavonoid metabolic process, which involves the following chalcone isomerase, flavonol synthase and anthocyanin synthasein. These proteins play important regulatory roles in anthocyanin biosynthesis and are the key regulators in anthocyanin accumulation. qRT-PCR was used to identify nine structural genes (PePAL2, PePAL4, PeC4H1, Pe4CL5, Pe4CL6, Pe4CL7, PeCHS2, PeCHS3 and PeUFGT2) playing key regulatory roles in anthocyanin synthesis in purple passion fruit pericarp. This study is expected to lay a foundation for the subsequent exploration of the regulatory mechanism of anthocyanin biosynthesis and the functional identification of related genes in passion fruit pericarp, and also to provide data support for the in-depth utilization of passion fruit resources.PMID:39778376 | DOI:10.1016/j.plaphy.2024.109441

Ecotoxicol Environ Saf. 2025 Jan 7;289:117692. doi: 10.1016/j.ecoenv.2025.117692. Online ahead of print.ABSTRACTExcessive copper (Cu) of rhizosphere inhibited the growth and development of citrus seedlings. Lignin deposition on the cell wall promotes plant Cu tolerance. However, the lignin biosynthesis in citrus leaves and roots that respond to Cu toxicity is not fully understood. In this study, young seedlings of 'Xuegan' [Citrus sinensis (L.) Osbeck, a less Cu-tolerant species] and 'Shatian pomelo' [Citrus grandis (L.) Osbeck, a more Cu-tolerant species] were treated with nutrient solution containing 0.5 (as Control), 100, 300 or 500 µM Cu for 15 weeks in sandy culture. By the end of treatments, citrus leaves and roots were sampled to investigate the biomass allocation, Cu distribution, the lignin biosynthesis and deposition. The results indicated that Cu stress from 100 to 500 µM increased the root/shoot biomass ratio, promoting Cu and lignin accumulation in the leaves and roots of the tested citrus species. Besides, 300 µM Cu stress increased the accumulation of three lignin monomers of citrus species. The metabolomic profile indicated that Cu toxicity altered the lignin components of citrus species. The citrus roots are more prominent in the lignin precursor biosynthesis under Cu toxicity than citrus leaves. The histochemical staining supported that Cu stress improved the deposition of both guaiacy and syringy lignin units in citrus roots. The enzyme activity and gene expression revealed that activating lignin-biosynthetic enzymes, such as L-phenylalanine ammonia-lyase, peroxidase and laccase, played an essential role in lignin biosynthesis. Our results demonstrated that excessive Cu induced lignin biosynthesis in citrus leaves and roots to different extents. The findings from the present study increased our understanding of lignin biosynthesis in Cu-stressed citrus species, which would provide a theoretical basis for the citrus Cu-tolerant mechanisms.PMID:39778317 | DOI:10.1016/j.ecoenv.2025.117692

Ecotoxicol Environ Saf. 2025 Jan 7;289:117689. doi: 10.1016/j.ecoenv.2025.117689. Online ahead of print.ABSTRACTIon beam mutagenesis is an advanced technique capable of inducing substantial changes in plants, resulting in noticeable alterations in their growth. However, the precise molecular mechanisms underlying the effects of radiation on soybeans remain unclear. This study investigates the impact of ionizing radiation on soybean development through a comprehensive approach that integrates transcriptomics and metabolomics. A total of 1500 rounds of disease-free soybean seeds underwent irradiation with 270 MeV/u 12C6+ ion beams, administered at doses of 0, 120, and 150 Gy. Our results revealed that key growth-related parameters, including plant height, branch number, number of pods per plant, and number of seeds per plant, were closely monitored and exhibited significant declines with increasing radiation doses. Transcriptomic analysis identified a multitude of differentially expressed genes (DEGs), with 6013, 3588, and 340 genes significantly altered in high vs. control, low vs. control, and high vs. low-dose irradiation comparisons, respectively, while metabolomic profiling unveiled 445, 445, and 218 differentially expressed metabolites (DEMs) in analogous comparisons. This comprehensive analysis ultimately pinpointed 123 key metabolites influenced by radiation stress. Putting together transcriptomic and metabolomic data showed strong connections between genes and metabolites, which had a big effect on pathways like pyruvate metabolism, ABC transporters, and glutathione metabolism. This underscores the comprehensive reprogramming of soybean metabolism to address irradiation-induced challenges. Specifically, we observed significant up-regulation of 24 DEGs, notable down-regulation of 8 DEMs, and significant activation of 15 metabolic pathways, all of which contributed to the observed phenotypic changes. These findings elucidate soybeans' complex molecular reactions to ionizing radiation, helping us understand how radiation-induced genetic and metabolic alterations affect plant growth.PMID:39778315 | DOI:10.1016/j.ecoenv.2025.117689

Plant Cell. 2025 Jan 8:koaf005. doi: 10.1093/plcell/koaf005. Online ahead of print.ABSTRACTMany C4 plants are used as food and fodder crops and often display improved resource use efficiency compared to C3 plants. However, the response of C4 plants to future extreme conditions such as heatwaves is less understood. Here, Setaria viridis, an emerging C4 model grass, was grown under long-term high temperature stress for two weeks (42°C, compared to 28°C). This resulted in stunted growth, but surprisingly had little impact on leaf thickness, leaf area-based photosynthetic rates and bundle sheath leakiness. Dark respiration rates increased and there were major alterations in carbon and nitrogen metabolism in the heat-stressed plants. Abscisic acid and indole-acetic acid-amino acid conjugates accumulated in the heat-stressed plants, consistent with transcriptional changes. Leaf transcriptomics, proteomics and metabolomics analyses were carried out and mapped onto the metabolic pathways of photosynthesis, respiration, carbon/nitrogen metabolism and phytohormone biosynthesis and signaling. An in-depth analysis of correlations between transcripts and their corresponding proteins revealed strong differences between groups in the strengths and signs of correlations. Overall, many stress signaling pathways were upregulated, consistent with multiple signals leading to reduced plant growth. A systems-based model of the plant response to long-term heat stress is presented based on the oxidative stress, phytohormone and sugar signaling pathways.PMID:39778116 | DOI:10.1093/plcell/koaf005

J Inherit Metab Dis. 2025 Jan;48(1):e12835. doi: 10.1002/jimd.12835.ABSTRACTInborn errors of metabolism (IEMs) are rare genetic conditions with significant morbidity and mortality. Technological advances have increased therapeutic options, making it challenging to remain up to date. A centralized therapy knowledgebase is needed for early diagnosis and targeted treatment. This study aimed to identify all treatable IEMs through a scoping literature review, followed by data extraction and analysis according to the Treatabolome principles. Knowledge of treatable IEMs, therapeutic categories, efficacy, and evidence was integrated into the Inborn Errors of Metabolism Knowledgebase (IEMbase), an online database encompassing all IEMs. The study identified 275 treatable IEMs, 18% of all currently known 1564 IEMs, according to the International Classification of Inherited Metabolic Disorders. Disorders of fatty acid and ketone body metabolism had the highest treatability (67%), followed by disorders of vitamin and cofactor metabolism (60%), and disorders of lipoprotein metabolism (42%). The most common treatment strategies were pharmacological therapy (34%), nutritional therapy (34%), and vitamin and trace element supplementation (12%). Treatment effects were most commonly observed in nervous system abnormalities (34%), metabolism/homeostasis abnormalities (33%), and growth (7%). Predominant evidence sources included case reports with evidence levels 4 (48%) and 5 (12%), and individual cohort studies with evidence level 2b (12%). Our study generated the Metabolic Treatabolome 2024. IEMs are the largest group of monogenic disorders amenable to disease-modifying therapy. With drug repurposing efforts and advancements in gene therapies, this number will expand. IEMbase now provides up-to-date, comprehensive information on clinical and biochemical symptoms and therapeutic options, empowering patients, families, healthcare professionals, and researchers in improving patient outcomes.PMID:39777714 | DOI:10.1002/jimd.12835

Nat Prod Bioprospect. 2025 Jan 8;15(1):11. doi: 10.1007/s13659-024-00495-3.ABSTRACTAnchusa italica Retz. (AIR), a traditional herbal remedy, is commonly applied in managing heart and brain disorders. However, its specific function and mechanism in acute cerebral ischemia-reperfusion injury (CIRI) are not fully understood. This research focused on the interventional effects and potential mechanisms of AIR extract (AIRE) in a rat model of CIRI. The model was established using the filament occlusion method, which involved blocking the middle cerebral artery for 1.5 h and then removing the filament to restore blood flow. Transcriptomic and metabolomic analyses were conducted to explore the molecular pathways and metabolites affected by AIRE. ATP level was measured using an ATP assay kit. Additionally, RT-qPCR and western blot tests were conducted to evaluate the influence of AIRE on the Wnt signaling pathway and mitochondrial function. Transcriptomic and metabolomic analyses indicated that AIRE regulated the Wnt signaling pathway in CIRI and modulated metabolites associated with mitochondrial energy metabolism, such as citrate and succinate. ATP assay result demonstrated that AIRE enhanced ATP production in CIRI. Further, RT-qPCR and western blot analyses revealed that AIRE activated the Wnt/β-catenin signaling pathway and corrected mitochondrial dysfunction. These results proposed that AIRE mitigated mitochondrial energy metabolism deficits in CIRI via the Wnt/β-catenin pathway. By restoring the balance of mitochondrial function and energy metabolism, AIRE might offer a potentially therapeutic strategy for addressing CIRI.PMID:39777624 | DOI:10.1007/s13659-024-00495-3

Front Endocrinol (Lausanne). 2024 Dec 24;15:1491411. doi: 10.3389/fendo.2024.1491411. eCollection 2024.ABSTRACTBACKGROUND AND OBJECTIVE: The incidence of central precocious puberty (CPP) in girls increased significantly during the COVID-19 pandemic. This study aimed to explore the impact of perfluorinated endocrine disruptors on CPP through metabolomics analysis in girls from Hainan Province, China.METHODS: Serum samples from 100 girls with CPP and 100 healthy controls were collected. Untargeted metabolomics profiling was performed using ultra-high performance liquid chromatography coupled with quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS). Differentially expressed metabolites (DEMs) were screened, and pathway enrichment analysis was conducted.RESULTS: Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) revealed distinct metabolic profiles between the CPP and control groups. A total of 511 metabolites were identified, including 296 up-regulated DEMs and 255 down-regulated DEMs. Three perfluorinated compounds-PFSM-perfluoroalkyl_sulfonamide_Me, PFSM-FSAA, and PFCA-unsaturated-were significantly upregulated in the CPP group. KEGG pathway enrichment analysis suggested the involvement of multiple pathways in the CPP process regulated by these compounds.CONCLUSIONS: Perfluorinated compounds may promote CPP in girls by interfering with various pathways and affecting the hypothalamic-pituitary-gonadal axis function. This study highlighted the need for further research and public health measures to address environmental endocrine disruptors.PMID:39777221 | PMC:PMC11703715 | DOI:10.3389/fendo.2024.1491411

Natl Sci Rev. 2024 Sep 30;12(1):nwae346. doi: 10.1093/nsr/nwae346. eCollection 2025 Jan.ABSTRACTCarbon-14 (C-14) has been a major contributor to the human radioactive exposure dose, as it is released into the environment from the nuclear industry in larger quantities compared to other radionuclides. This most abundant nuclide enters the biosphere as organically bound C-14 (OBC-14), posing a potential threat to public health. Yet, it remains unknown how this relatively low radiotoxic nuclide induces health risks via chemical effects, such as isotope effect. By establishing a trophic transfer model involving algae (Scenedesmus obliquus), daphnia (Daphnia magna) and zebrafish (Danio rerio), we demonstrate that rapid incorporation and transformation of inorganic C-14 by algae into OBC-14 facilitates the blending of C-14 into the biomolecules of zebrafish. We find that internalized C-14 is persistently retained in the brain of zebrafish, affecting DNA methylation and causing alterations in neuropathology. Global isotope tracing metabolomics with C-14 exposure further reveals the involvement of C-14 in various critical metabolic pathways, including one-carbon metabolism and nucleotide metabolism. We thus characterize the kinetic isotope effects for 12C/14C in the key reactions of these metabolic pathways through kinetic experiments and density functional theory computations, showing that the isotopic substitution of carbon in biochemicals regulates metabolism by disrupting reaction ratios via isotope effects. Our results suggest that inorganic C-14 discharged by the nuclear industry can be biotransformed into OBC-14 to impact metabolism via isotope effects, providing new insights into understanding the health risk of C-14, which is traditionally considered as a low radiotoxic nuclide.PMID:39777205 | PMC:PMC11706001 | DOI:10.1093/nsr/nwae346

Front Microbiol. 2024 Dec 24;15:1348403. doi: 10.3389/fmicb.2024.1348403. eCollection 2024.ABSTRACTOBJECTIVE: This study aimed to explore the changes in gut microbiota and its metabolites in different pathophysiological stages of doxorubicin (DOX)-induced heart failure (DIHF) and the relationship between gut microbiota and metabolites in various degrees of DIHF.MATERIALS AND METHODS: C57BL/6 J mice were injected intraperitoneally with 5 mg/kg of DOX once a week for 5 consecutive weeks. At different times after injection, the cardiac function and histopathological analysis was conducted, the serum levels of creatine kinase (CK), CK-MB, lactic dehydrogenase, and cardiac troponin T were determined. 16S rRNA gene sequencing of feces and the nontargeted metabolomics analysis of serum were performed. Multi-omics analyses were used to explore the correlation between gut microbiota and serum metabolites.RESULTS: The results showed that DOX caused cardiac contractile dysfunction and left ventricular (LV) dilation. The levels of myocardial enzymes significantly increase in 3 and 5 weeks after DOX injection. DOX-treated mice showed significant differences in the composition and abundance of gut microorganisms, and the levels of serum metabolites at different times of treatment. Multi-omics analyses showed that intestinal bacteria were significantly correlated with the differential metabolites. Some bacteria and metabolites can be used as biomarkers of DIHF (AUC > 0.8). KEGG analyses showed the involvement of different metabolic pathways in various degrees of DIHF.CONCLUSION: Marked differences were found in the composition and abundance of gut microorganisms, the levels of serum metabolites and metabolic pathways in different degrees of DIHF. The intestinal bacteria were significantly correlated with differential metabolites in different degrees of DIHF. The gut microbiota may serve as new targets for the treatment of DIHF.PMID:39777147 | PMC:PMC11703658 | DOI:10.3389/fmicb.2024.1348403

Metabolomics. 2015 Oct;11(5):1327-1337. doi: 10.1007/s11306-015-0787-6. Epub 2015 Feb 21.ABSTRACTBoth metabolomic and genomic approaches are valuable for risk analysis, however typical approaches evaluating differences in means do not model the changes well. Gene polymorphisms that alter function would appear as distinct populations, or metabotypes, from the predominant one, in which case risk is revealed as changed mixing proportions between control and case samples. Here we validate a model accounting for mixed populations using biomarkers of fatty acid metabolism derived from a case/control study of acute coronary syndrome subjects in which both metabolomic and genomic approaches have been used previously. We first used simulated data to show improved power and sensitivity in the approach compared to classic approaches. We then used the metabolic biomarkers to test for evidence of distinct metabotypes and different proportions among cases and controls. In simulation, our model outperformed all other approaches including Mann-Whitney, t-tests, and χ2. Using real data, we found distinct metabotypes of six of the seven activities tested, and different mixing proportions in five of the six activity biomarkers: D9D, ELOVL6, ELOVL5, FADS1, and Sprecher pathway chain shortening (SCS). High activity metabotypes of non-essential fatty acids and SCS decreased odds for acute coronary syndrome (ACS), however high activity metabotypes of 20-carbon fatty acid synthesis increased odds. Our study validates an approach that accounts for both metabolomic and genomic theory by demonstrating improved sensitivity and specificity, better performance in real world data, and more straightforward interpretability.PMID:39777108 | PMC:PMC11706515 | DOI:10.1007/s11306-015-0787-6

Aging Med (Milton). 2024 Dec 30;7(6):689-698. doi: 10.1002/agm2.12376. eCollection 2024 Dec.ABSTRACTOBJECTIVES: This study aimed to determine whether type 2 diabetes (T2D) is an independent risk factor for sleep disorders in the elderly and explore the possible intestinal flora factors of sleep disorders combined with T2D in this population.METHODS: All hospitalized patients with sleep disorders aged ≥65 years between June and November 2023 were retrospectively analyzed, and they were divided into a sleep disorder group (n = 134) and a control group (n = 109). The logistic regression method was utilized to clarify the causal relationship between T2D and sleep disorders. For stool analyses, 42 patients were randomly extracted, which included the control group (n = 14), diabetes group (n = 14), and elderly patients with sleep disorders combined with the T2D group (ESdD) (n = 14). The composition feature of intestinal flora and metabolomics in the ESdD group was described through high-throughput 16S rDNA sequencing and nontargeted analysis based on liquid chromatography-mass spectrometry.RESULTS: Gender, body mass index (BMI), T2D, intestinal discomfort, and anxiety depression were independent risk factors for sleep disorders in the elderly. Notably, older individuals with T2D were 3.3 times more likely to experience sleep disorders than normal individuals. Compared with the control group, the ESdD group had decreased relative abundance of Barnesiella and Marvinbryantia, with 47 metabolites upregulated and 53 metabolites downregulated. The ESdD group showed a decrease in Lachnospiraceae_UCG_010, with 62 metabolites upregulated and 43 metabolites downregulated, compared with the diabetes group.CONCLUSIONS: Diabetes is an independent risk factor for sleep disorders in the elderly patients. Variations in intestinal flora and metabolism significantly influence the onset and progression of the ESdD group.PMID:39777104 | PMC:PMC11702488 | DOI:10.1002/agm2.12376

Aging Med (Milton). 2024 Dec 23;7(6):744-753. doi: 10.1002/agm2.12377. eCollection 2024 Dec.ABSTRACTOBJECTIVES: To outline the design of the P3 study and serve as a summary of the interim baseline patient characteristics.METHODS: P3 study is a multicenter, prospective cohort study targeting 1000 acute ischemic stroke (AIS) and cerebral small vessel disease (CSVD) patients with a 2-year follow-up from 80 participating hospitals across China. Comprehensive multimodal imaging, neuropsychological tests, and biological samples were collected prospectively on admission and follow-up visits. Patients were interviewed face to face for 2 years and followed up.RESULTS: Until 30 December 2023, 642 patients were enrolled from 67 centers. In the AIS cohort, 219 patients (72.5%) were diagnosed with acute post-stroke cognitive impairment (PSCI). Compared to those without PSCI, the acute PSCI group exhibited significantly lower levels of education and a history of stroke (all P < 0.05). In the CSVD cohort, 53 patients (41.4%) were diagnosed with cognitive impairment. Compared to those with normal cognitive function, the impaired cognitive function group had a significantly higher prevalence of hypertension and diabetes history (all P < 0.05). All 642 patients completed 20 tests, as well as clinical information and blood sample collection. Nearly 95% of the patients underwent structural MRI and ASL, and 60% of patients completed fMRI and DKI or DTI.CONCLUSIONS: P3 study aims to establish a comprehensive spatiotemporal profile of VCI. Through multidimensional analysis of clinical information, radiomics, proteomics, metabolomics, microbiomics, and genetics, provide a more comprehensive understanding of VCI trajectories and individual variability, enhancing early detection and prognosis management.PMID:39777092 | PMC:PMC11702399 | DOI:10.1002/agm2.12377

Front Plant Sci. 2024 Dec 24;15:1459533. doi: 10.3389/fpls.2024.1459533. eCollection 2024.ABSTRACTMedicinal plants are important sources of bioactive specialized metabolites with significant therapeutic potential. Advances in multi-omics have accelerated the understanding of specialized metabolite biosynthesis and regulation. Genomics, transcriptomics, proteomics, and metabolomics have each contributed new insights into biosynthetic gene clusters (BGCs), metabolic pathways, and stress responses. However, single-omics approaches often fail to fully address these complex processes. Integrated multi-omics provides a holistic perspective on key regulatory networks. High-throughput sequencing and emerging technologies like single-cell and spatial omics have deepened our understanding of cell-specific and spatially resolved biosynthetic dynamics. Despite these advancements, challenges remain in managing large datasets, standardizing protocols, accounting for the dynamic nature of specialized metabolism, and effectively applying synthetic biology for sustainable specialized metabolite production. This review highlights recent progress in omics-based research on medicinal plants, discusses available bioinformatics tools, and explores future research trends aimed at leveraging integrated multi-omics to improve the medicinal quality and sustainable utilization of plant resources.PMID:39777086 | PMC:PMC11703845 | DOI:10.3389/fpls.2024.1459533

Front Pharmacol. 2024 Dec 24;15:1504109. doi: 10.3389/fphar.2024.1504109. eCollection 2024.ABSTRACTINTRODUCTION: Stroke is a debilitating disease and the second leading cause of death worldwide, of which ischemic stroke is the dominant type. Carthamus tinctorius L., also known as safflower, has been used to treat cerebrovascular diseases, especially ischemic stroke in many Asian countries. However, the underlying mechanisms of safflower in preventing ischemic stroke remains elusive. This study aims to elucidate the potential of safflower as a drug candidate for the prevention of ischemic stroke and to delineate its protective effects and potential mechanisms in a rat model of cerebral ischemia-reperfusion injury (CI/RI).METHODS: The aqueous extract of safflower (AESF) was verified using HPLC-UV, HPLC-MS, and TLC. The inhibitory effect of AESF on platelet aggregation was detected in vitro and in zebrafish and mice. A CI/RI model in rats was established by middle cerebral artery occlusion and reperfusion to study the protective effect of AESF on ischemic stroke. 2,3,5-triphenyltetrazolium chloride, hematoxylin and eosin, and Nissl's staining were employed to evaluate the pathological changes of brain tissue. In addition, metabolomics, ELISA, and Western blot were used to uncover the molecular alteration induced by AESF.RESULTS: AESF significantly inhibited platelet aggregation in vitro, reduced the thrombogenesis in zebrafish, and prolonged clotting time in mice. In addition, AESF alleviated neurological dysfunction, cerebral oedema, cerebral infarct size, cerebral histopathological damage induced by ischemia-reperfusion, improved neuronal survival, increased serum levels of SOD and CAT, and decreased levels of iNOS and NO. Metabolomics revealed that AESF attenuated the metabolic disturbances in brain caused by I/R injury via regulating 38 metabolites particularly related to the arachidonic acid (AA) metabolism. Moreover, AESF elevated the serum levels of 6-keto-PGF1α, a pivotal metabolite of AA, downregulated the protein expression of p53, Bax, cleaved caspase-9, cleaved caspase-3, and cleaved caspase-8, and upregulated that of Bcl-2.CONCLUSION: AESF mitigated CI/RI through preventing platelet aggregation, alleviating oxidative stress, and suppressing apoptosis partially via modulating AA metabolism/p53-mediated apoptosis axis.PMID:39776584 | PMC:PMC11703823 | DOI:10.3389/fphar.2024.1504109

Front Pharmacol. 2024 Dec 24;15:1516272. doi: 10.3389/fphar.2024.1516272. eCollection 2024.ABSTRACTINTRODUCTION: The aim of this study is to examine the physiological effects of emodin on intestinal microorganisms and the liver in the BALb/c mice.METHOD AND RESULTS: Following an 8-week administration of emodin at doses of 25, 50, and 100 mg/kg/day,pathological analyses revealed that emodin significantly reduced the colon length, induced colonic crypt inflammation,diminished the colonic mucus layer,and decreased the fluorescence intensity of colonic tight junction proteins ZO-1 and Occludin. Concurrently, 16S rDNA gene sequencing corroborated that emodin altered the diversity and composition of the intestinal microbiota by increasing the Firmicutes to Bacteroides ratio. Simultaneously, the non-targeted metabolomics analyses exhibited significant alternations in both short chain fatty acids and free fatty acids between the emodin-treated and the normal groups, indicating emodin-induced disturbance in intestinal metabolic disorder. Furthermore, emodin exhibited a significant elevation in LPS levels in colon, serum and liver as well an marked increase in the levels of TC, TG, AST, and ALT in serum. Additionally, histological examination employing by HE and oil-red O staining furtherly verified that the administration of varying doses emodin induced hepatic inflammation and lipid accumulation. Whereas qRT-PCR and Western blot analyses demonstrated that the administering of varying doses of emodin upregulated the mRNA levels of TNF-α, IL-1β, IL-6, and IL-18 as well as the expression of TLR4, Myd88, and P-65. Following the combined administration of probiotics, the high-dose emodin did not significantly influence ALT and AST levels in mice. However, the faeces of the high-dose emodin transplanted in mice and induced a significant increase in AST levels and in the relative abundance of Firmicutes and Proteobacteria.DISCUSSION: These findings further corroborate that emodin induces liver injury via the intestinal dysfunction. These findings suggested that emodin may disrupt intestinal microbiota and resulted in significant alternations in endogenous metabolites in mice, thereby facilitating the entry of LPS and FFAs into the liver, potentially leading to hepatic injury.PMID:39776579 | PMC:PMC11703826 | DOI:10.3389/fphar.2024.1516272

Front Public Health. 2024 Dec 24;12:1490647. doi: 10.3389/fpubh.2024.1490647. eCollection 2024.ABSTRACTINTRODUCTION: The transition from low to high altitude environments is associated with a multifaceted series of physiological and psychological alterations that manifest over time. These changes are intricately intertwined, with physiological acclimatization primarily mediated through the regulation of hypoxia-inducible factor (HIF), which orchestrates the expression of critical molecules and hormones. This process extends to encompass the epigenome, metabolism, and other regulatory mechanisms. In the realm of psychological acclimatization, chronic hypoxia and changes in atmospheric pressure at high altitudes may contribute to decreased levels of neurotransmitters, with potential implications for mental health, particularly in relation to sleep quality. Despite significant advancements in our understanding of plateau acclimatization mechanisms in recent years, there remain many uncertain factors that necessitate further research.METHODS: This study is a single-center prospective observational study. It aims to utilize a series of physiological and medical instruments in conjunction with internationally recognized physiological and psychological questionnaires to monitor the dynamic shifts in the acclimatization ability of doctors from Peking Union Medical College Hospital. The monitoring will occur at seven distinct time points: pre-departure from Beijing, 1-7 days post-arrival at the Tibetan plateau during the acute phase of plateau hypoxic stress, and during the chronic phase of plateau hypoxic stress at 2 weeks, 3 months, 6 months, 12 months of residency in Tibet, and post-return to Beijing. Concurrently, a spectrum of omics analyses will be conducted, including comprehensive genomic, proteomic, and metabolomic assessments of blood leukocytes, fecal, and oral samples.PMID:39776479 | PMC:PMC11703865 | DOI:10.3389/fpubh.2024.1490647