PubMed

Brief Bioinform. 2025 Mar 4;26(2):bbaf088. doi: 10.1093/bib/bbaf088.ABSTRACTParkinson's disease (PD) is a complex, progressive neurodegenerative disorder with high heterogeneity, making early diagnosis difficult. Early detection and intervention are crucial for slowing PD progression. Understanding PD's diverse pathways and mechanisms is key to advancing knowledge. Recent advances in noninvasive imaging and multi-omics technologies have provided valuable insights into PD's underlying causes and biological processes. However, integrating these diverse data sources remains challenging, especially when deriving meaningful low-level features that can serve as diagnostic indicators. This study developed and validated a novel integrative, multimodal predictive model for detecting PD based on features derived from multimodal data, including hematological information, proteomics, RNA sequencing, metabolomics, and dopamine transporter scan imaging, sourced from the Parkinson's Progression Markers Initiative. Several model architectures were investigated and evaluated, including support vector machine, eXtreme Gradient Boosting, fully connected neural networks with concatenation and joint modeling (FCNN_C and FCNN_JM), and a multimodal encoder-based model with multi-head cross-attention (MMT_CA). The MMT_CA model demonstrated superior predictive performance, achieving a balanced classification accuracy of 97.7%, thus highlighting its ability to capture and leverage cross-modality inter-dependencies to aid predictive analytics. Furthermore, feature importance analysis using SHapley Additive exPlanations not only identified crucial diagnostic biomarkers to inform the predictive models in this study but also holds potential for future research aimed at integrated functional analyses of PD from a multi-omics perspective, ultimately revealing targets required for precision medicine approaches to aid treatment of PD aimed at slowing down its progression.PMID:40062615 | DOI:10.1093/bib/bbaf088

Cancer Med. 2025 Mar;14(5):e70658. doi: 10.1002/cam4.70658.ABSTRACTBACKGROUND: Enhanced protein expression of ALL1-fused gene from chromosome 1q (AF1Q) after (chemo)radiotherapy has been described in vitro, but is largely understudied in gastrointestinal cancer. We aimed to investigate AF1q expression in rectal cancer (RC) patients treated with short-term radiation therapy and a possible correlation with markers crucial for RC prognosis.METHODS: A cohort of 75 RC patients scheduled for surgery was defined and patients with moderately locally advanced tumors (cT3Nx) received preoperative hyperfractionated short-term radiation therapy (cumulative dose 25 Gy). Immunohistochemical analysis was conducted to assess AF1q, STAT1, IDO1 and other prognostic markers (CD3/CD8-Immunoscore, PD-L1) and marker correlations were evaluated.RESULTS: Irradiated tumors exhibited significantly higher AF1q expression than treatment-naïve samples (n = 60: AF1q + to AF1q+++ 98.3% (n = 59), AF1q- 1.7% (n = 1) vs. n = 15: AF1q + 78.6% (n = 11), AF1q- 21.4% (n = 4); p < 0.001). Specifically, irradiated tumors showed high STAT1, but low IDO1 expression compared to treatment-naïve samples (p = 0.019 and p = 0.015, respectively). Overall, enhanced tumoral AF1q expression was associated with negative lymph node stage (p = 0.012) as well as with diminished expression of STAT1 (rs = -0.468, p = 0.038) and IDO1 (rs = -0.246, p = 0.020).CONCLUSION: AF1q is expressed in RC, especially after short-term radiation therapy. Here, AF1q may support tumor suppression, possibly through the involvement of the pro-apoptotic STAT1 axis. Further mechanistic evidence and investigation involving a larger patient cohort are needed to validate a radiation-induced, AF1q-driven tumor-suppressing effect, which may impact RC patient outcomes.PMID:40062505 | DOI:10.1002/cam4.70658

Research (Wash D C). 2025 Mar 8;8:0628. doi: 10.34133/research.0628. eCollection 2025.ABSTRACTCardiovascular diseases constitute a marked threat to global health, and the emergence of spatial omics technologies has revolutionized cardiovascular research. This review explores the application of spatial omics, including spatial transcriptomics, spatial proteomics, spatial metabolomics, spatial genomics, and spatial epigenomics, providing more insight into the molecular and cellular foundations of cardiovascular disease and highlighting the critical contributions of spatial omics to cardiovascular science, and discusses future prospects, including technological advancements, integration of multi-omics, and clinical applications. These developments should contribute to the understanding of cardiovascular diseases and guide the progress of precision medicine, targeted therapies, and personalized treatments.PMID:40062231 | PMC:PMC11889335 | DOI:10.34133/research.0628

Curr Pharmacol Rep. 2025;11(1):12. doi: 10.1007/s40495-025-00396-0. Epub 2025 Feb 6.ABSTRACTPURPOSE OF REVIEW: In this review article, specific emphasis is on evolution of metabolomics in cancer research, metabolomics workflow, general understanding of liquid chromatography - mass spectrometry (LC-MS) based platform for quantitation of metabolites, their biological interpretation and the application in carcinogenesis and cancer prevention by dietary phytochemicals.RECENT FINDINGS: Metabolomics is increasingly becoming a preferred approach for next generation metabolic screening and has profound impact on medical practice. Metabolomics describes the end products of biochemical processes which are greatly influenced by genetic and environmental factors. Metabolic alterations can be linked to potential biochemical reactions/enzymes and their corresponding genes. Thus, these results can be further validated via multi-omics approach including genomics, transcriptomics and proteomics. However, challenges exist within and between omic-domain data integration considering complex biochemical regulation including organism versus tissue versus cellular level processes, epigenetics, transcriptional and post translational modifications. Metabolomics can reflect the steady state or dynamic state of metabolism because metabolites are highly dynamic in space and time.SUMMARY: Metabolomic analysis of biological samples exhibit the possibility to determine mechanism of action of anti-cancer agents, biomarker discovery and impact of genetic alterations.PMID:40062208 | PMC:PMC11889054 | DOI:10.1007/s40495-025-00396-0

Phenomics. 2024 Oct 16;4(6):584-591. doi: 10.1007/s43657-024-00196-4. eCollection 2024 Dec.ABSTRACTThe TRacing Etiology of Non-communicable Diseases (TREND) cohort is a prospective longitudinal cohort and biobank that is mainly based in Ma'anshan, Anhui Province, China. The primary aim of the study is to decipher comprehensive molecular characterization and deep phenotyping for a broad spectrum of chronic non-communicable diseases (NCDs), which focuses on providing mechanistic insights with diagnostic, prognostic and therapeutic implications. The recruitment was initiated in 2023 and is expected to complete in 2025 with 20,000 participants originated from urban and rural area. In the first phase, 3360 participants were recruited. Follow-up visits are scheduled annually and intervally for a total of 30 years. The cohort includes individuals aged over 18 years. Two participants with first-degree linkage were recruited from a household. The age distribution of recruited participants was stratified into four categories: 18-45, 45-55, 55-65, and ≥65 years, aligning with the population proportions of Ma'anshan. Meanwhile, the gender distribution was controlled by pairing men and women from the same household. Data collected at baseline includes socio-economic information, medical history, lifestyle and nutritional habits, anthropometrics, blood oxygen, electrocardiogram (ECG), heart sound, as well as blood, urine and feces tests results. Molecular profiling includes genome, proteome, metabolome, microbiome and extracellular vesicles -omics. Blood, urine and fecal samples are collected and stored at -80 °C in a storage facility for future research.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-024-00196-4.PMID:40061819 | PMC:PMC11889304 | DOI:10.1007/s43657-024-00196-4

Hortic Res. 2024 Dec 12;12(3):uhae348. doi: 10.1093/hr/uhae348. eCollection 2025 Mar.ABSTRACTCurcuma alismatifolia is an important ornamental plant of significant economic value, while the floral fragrance has been rarely investigated, leading to a lack of knowledge about the floral scent. By performing metabolomic and transcriptomic analyses, we investigated the variation of 906 volatile organic compounds (VOCs) in florets of eight C. alismatifolia cultivars and four different developmental stages of "Chiang Mai Pink" (CMP). The metabolite profiling revealed that the terpenoid group (213 out of 906) was the predominant VOC, accounting for 33.5% and 43.4% of total VOC contents in the florets of different cultivars and developmental stages, respectively. Sweet and woody were the predominant odors not only in different cultivars but also during developmental stages. The varied intensities of other odors contributed to forming odor diversities in C. alismatifolia floret. We uncovered seven terpenoid synthetase (TPS) genes and four MYB genes of significant association with the biosynthesis of terpenoids in eight cultivars and floret development, respectively. We performed an activity assay on four selected TPS genes and identified that Chr15HA1352 and Chr15HA2528 are responsible for the biosynthesis of α-farnesene. The significant association between the MYB gene (Chr03HA28) and seven terpenoids can be observed among different cultivars and during different developmental stages. These findings highlight the varying floral scents in different cultivars and floret development and suggest the potential roles of identified TPS and MYB genes in the biosynthesis of terpenoids in C. alismatifolia.PMID:40061800 | PMC:PMC11890029 | DOI:10.1093/hr/uhae348

medRxiv [Preprint]. 2025 Feb 27:2025.02.26.25322932. doi: 10.1101/2025.02.26.25322932.ABSTRACTWe investigated genetic regulators of circulating plasma metabolites to identify pathways underlying biochemical changes in clinical and biomarker-assisted diagnosis of Alzheimer's disease (AD). We computed metabolite quantitative trait loci by using whole genome sequencing and small molecule plasma metabolites from 229 older adults with clinical AD and 322 age-matched healthy controls. Unbiased associations between 6,881 metabolites and 332,772 common genetic variants were tested, adjusted for age, sex, and both metabolomic and genomic principal components. We identified 72 novel and known SNP-metabolite associations spanning 66 genes and 12 metabolite classes, including PYROXD2 and N6-methyllysine, FAAH and myristoylglycine, as well as FADS2 and arachidonic acid. In addition, we found differences in genetic regulation of metabolites among individuals with clinically defined AD compared to AD defined by a published plasma P-tau181 level cut-off. We also found more SNP-metabolite associations among males compared to females. In summary, we identified sex- and disease-specific genetic regulators of plasma metabolites and unique biological mechanisms of genetic perturbations in AD.PMID:40061336 | PMC:PMC11888523 | DOI:10.1101/2025.02.26.25322932

medRxiv [Preprint]. 2025 Feb 28:2025.02.27.25321444. doi: 10.1101/2025.02.27.25321444.ABSTRACTBACKGROUND: Metabolomic dysregulation contributes to prostate cancer (PCa) pathogenesis, and studies suggest that circulating metabolites have strong clinical potential to act as biomarkers. However, evidence of circulating metabolite associations has not been quantitively aggregated.METHODS: Systematic searches were performed in PubMed and Embase (October 17 th , 2024) to identify pre-diagnostic untargeted serum metabolomic studies of PCa risk. After harmonizing metabolite names across studies, restricted maximum likelihood was used to conduct meta-analyses to quantify associations between metabolites and risk of overall PCa, low- to intermediate-risk PCa, high- to very high-risk PCa and lethal PCa, as defined by the NCCN. Statistical significance was defined as FDR-adjusted P<0.05. Enrichment analyses were conducted on significant metabolites to identify biologically relevant pathways. Correlation of effect estimates between PCa outcomes was assessed via Pearson correlation.RESULTS: We identified 12 untargeted pre-diagnostic circulating metabolomic studies in a systematic review and meta-analyzed associations between up to 408 metabolites with four PCa outcomes. Three, eleven and nineteen metabolites were significantly associated with risk of overall, high/very high-risk and lethal PCa, respectively. Metabolites associated with high/very high-risk PCa were significantly enriched for lipids. Limited evidence of correlation between metabolite effects across outcomes was identified, highlighting potentially unique metabolite drivers of high-risk and lethal PCa. Follow-up analyses found that 13 of the significant metabolites were drug and/or dietary modifiable.CONCLUSIONS: These findings suggest the strong potential for metabolites to inform risk of lethal PCa, which could inform risk-stratified screening strategies and facilitate the identification of targets for PCa prevention.PMID:40061317 | PMC:PMC11888532 | DOI:10.1101/2025.02.27.25321444

Mater Today Bio. 2025 Feb 15;31:101566. doi: 10.1016/j.mtbio.2025.101566. eCollection 2025 Apr.ABSTRACTInduced pluripotent stem cells (iPSCs), carrying the patient's genetic background, open the path to advanced in vitro modeling. The feasibility of recapitulating complex pathophysiological scenarios depends on iPSC's ability to differentiate into the plurality of specific organ resident cells, on their maturation and networking. To this end, a strong interest has arisen in organoids, 3D structures, obtained by exploiting iPSC natural capability to self-assemble and rebuild organ parts. In this study, we describe the characterization of a novel iPSC-based cardiac organoid (CO) model, generated by a high-throughput and cost-effective method. Organoids were obtained by culture onto substrates of known stiffness, under geometrical confinement and inducing cardiac differentiation by small-molecule-based modulation of Wnt pathway. COs were characterized using a multi-omic approach (including bulk/single-cell RNA-sequencing, and proteomic analysis), immunofluorescence, electrophysiology (patch clamp), and optical recording-based contraction measurements. Results showed that COs recapitulate relevant cardiac features, including spontaneous contraction, multicellularity (e.g., cardiomyocytes, fibroblasts, epicardial layer) and chamber organization. Moreover, modulation of environmental mechanical cues showed a significant effect on organoid cardiac features. In particular, culturing organoids onto substrates of low stiffness, in the range of that characterizing the embryonal surrounding, enriched the gene sets related to cardiac maturity and cardiomyocyte ultrastructure. Functionally, different cardiac-specific ionic currents and consistent spontaneous action potentials were recorded upon patch-clamp of cardiomyocytes dissociated from COs. Finally, the beating rate of the whole COs was monitored non-destructively via video recording and quantified, demonstrating their response to clinically used chronotropic compounds, supporting the feasibility of future implementation of the proposed COs as in vitro platform for drug testing.PMID:40061214 | PMC:PMC11889630 | DOI:10.1016/j.mtbio.2025.101566

ACS Omega. 2025 Feb 18;10(8):7597-7608. doi: 10.1021/acsomega.4c00645. eCollection 2025 Mar 4.ABSTRACTMicroplastics are plastic particles with sizes of less than 5 mm. The ubiquity of microplastics in the environment has raised serious public health concerns. Microplastics could disturb the composition of the gut microbiota due to both chemical composition and physical interactions, which might further influence the metabolism and immune function of the host. However, most of the exposure studies chose microplastics of specific sizes. In the natural environment, living organisms are exposed to a mixture of microplastics of various sizes. In this study, male C57BL/6 mice were exposed to polystyrene (PS) microplastics with different sizes, including microplastics with diameters of 0.05-0.1 μm (PS0.1 group, 100 ppb), 9-10 μm (PS10 group, 100 ppb), and microplastic mixtures of both 0.05-0.1 and 9-10 μm (PSMix group) at a total concentration of 100 ppb (50 ppb for each size). Mixture effects of microplastics were investigated on the composition of bacteria and fungi as well as functional metagenome and microbial genes encoding antibiotic resistance and virulence factors. We found that some bacteria, fungi, and microbial metabolic pathways were only altered in the PSMix group, not in the PS0.1 or PS10 group, suggesting the toxic effects of the microplastic mixture on the composition of fungi and bacteria, and the functional metagenome is different from the effects of microplastics at specific sizes. Meanwhile, altered genes encoding antibiotic resistance and virulence factors in the PSMix group were shared with the PS0.1 and PS10 groups, possibly due to functional redundancy. Our findings help improve the understanding of the toxic effects of the microplastic mixture on the gut microbiome.PMID:40060808 | PMC:PMC11886427 | DOI:10.1021/acsomega.4c00645

bioRxiv [Preprint]. 2025 Mar 1:2025.02.25.640178. doi: 10.1101/2025.02.25.640178.ABSTRACTAlzheimer's disease (AD) risk and progression are significantly influenced by APOE genotype with APOE4 increasing and APOE2 decreasing susceptibility compared to APOE3. While the effect of those genotypes was extensively studied on blood metabolome, less is known about their impact in the brain. Here we investigated the impacts of APOE genotypes and aging on brain metabolic profiles across the lifespan, using human APOE-targeted replacement mice. Biocrates P180 targeted metabolomics platform was used to measure a broad range of metabolites probing various metabolic processes. In all genotypes investigated we report changes in acylcarnitines, biogenic amines, amino acids, phospholipids and sphingomyelins during aging. The decreased ratio of medium to long-chain acylcarnitine suggests a reduced level of fatty acid β-oxidation and thus the possibility of mitochondrial dysfunction as these animals age. Additionally, aging APOE2/2 mice had altered branch-chain amino acids (BCAA) profile and increased their downstream metabolite C5 acylcarnitine, indicating increased branched-chain amino acid utilization in TCA cycle and better energetic profile endowed by this protective genotype. We compared these results with human dorsolateral prefrontal cortex metabolomic data from the Religious Orders Study/Memory and Aging Project, and we found that the carriers of APOE2/3 genotype had lower markers of impaired BCAA katabolism, including tiglyl carnitine, methylmalonate and 3-methylglutaconate. In summary, these results suggest a potential involvement of the APOE2 genotype in BCAA utilization in the TCA cycle and nominate these humanized APOE mouse models for further study of APOE in AD, brain aging, and brain BCAA utilization for energy. We have previously shown lower plasma BCAA to be associated with incident dementia, and their higher levels in brain with AD pathology and cognitive impairment. Those findings together with our current results could potentially explain the AD-protective effect of APOE2 genotype by enabling higher utilization of BCAA for energy during the decline of fatty acid β-oxidation.PMID:40060656 | PMC:PMC11888404 | DOI:10.1101/2025.02.25.640178

bioRxiv [Preprint]. 2025 Mar 2:2025.02.26.640463. doi: 10.1101/2025.02.26.640463.ABSTRACTUnderstanding how cellular pathways interact is crucial for treating complex diseases like cancer, yet our ability to map these connections systematically remains limited. Individual gene-gene interaction studies have provided insights 1,2 , but they miss the emergent properties of pathways working together. To address this challenge, we developed a multi-gene approach to pathway mapping and applied it to CRISPR data from the Cancer Dependency Map 3 . Our analysis of the electron transport chain revealed certain blood cancers, including acute myeloid leukemia (AML), depend on an unexpected link between Complex II and purine metabolism. Through stable isotope metabolomic tracing, we found that Complex II directly supports de novo purine biosynthesis and exogenous purines rescue AML from Complex II inhibition. The mechanism involves a metabolic circuit where glutamine provides nitrogen to build the purine ring, producing glutamate that Complex II must oxidize to sustain purine synthesis. This connection translated to a metabolic vulnerability whereby increasing intracellular glutamate levels suppresses purine production and sensitizes AML to Complex II inhibition. In mouse models, targeting Complex II triggered rapid disease regression and extended survival in aggressive AML. The clinical relevance of this pathway emerged in human studies, where higher Complex II gene expression correlates with both resistance to mitochondria-targeted therapies and worse survival outcomes specifically in AML patients. These findings establish Complex II as a central regulator of de novo purine biosynthesis and identify it as a promising therapeutic target in AML.PMID:40060603 | PMC:PMC11888402 | DOI:10.1101/2025.02.26.640463

bioRxiv [Preprint]. 2025 Feb 26:2024.05.03.592475. doi: 10.1101/2024.05.03.592475.ABSTRACTDecline in ovarian function with age not only affects fertility but is also linked to a higher risk of age-related diseases in women ( e.g . osteoporosis, dementia). Intriguingly, earlier menopause is linked to shorter lifespan; however, the underlying molecular mechanisms of ovarian aging are not well understood. Recent evidence suggests the gut microbiota may influence ovarian health. In this study, we characterized ovarian aging associated microbial profiles in mice and investigated the effect of the gut microbiome from young and estropausal female mice on ovarian health through fecal microbiota transplantation. We demonstrate that the ovarian transcriptome can be broadly remodeled after heterochronic microbiota transplantation, with a reduction in inflammation-related gene expression and trends consistent with transcriptional rejuvenation. Consistently, these mice exhibited enhanced ovarian health and increased fertility. Using metagenomics-based causal mediation analyses and serum untargeted metabolomics, we identified candidate microbial species and metabolites that may contribute to the observed effects of fecal microbiota transplantation. Our findings reveal a direct link between the gut microbiota and ovarian health.PMID:40060387 | PMC:PMC11888174 | DOI:10.1101/2024.05.03.592475

aBIOTECH. 2025 Feb 18;6(1):33-49. doi: 10.1007/s42994-025-00199-3. eCollection 2025 Mar.ABSTRACTPotato common scab (CS) is a worldwide disease, caused by Streptomyces spp., and its presence reduces the market value of potatoes. A nontoxic and potentially effective approach in many control strategies is the use of antagonistic microbes as biocontrol agents. In this study, Bacillus atrophaeus DX-9 was isolated and assessed for its ability to protect against CS. Through integrated metagenomic and metabolomic analyses, changes in the soil microbial community structure and soil properties were analyzed to understand the effects of Bacillus atrophaeus DX-9 on CS. These studies revealed that DX-9 inoculation could significantly decrease CS disease rate, disease index, and the number of CS pathogens, along with an increase in soil N and P content. Our metagenomic assays identified 102 phyla and 1154 genera, and DX-9 inoculation increased the relative abundances of the phyla Pseudomonadota, Chloroflexota and Gemmatimonadota. Additionally, an increase in the relative abundance of genera, such as Bradyrhizobium, Agrobacterium, and Nitrobacter, were significantly and positively correlated with soil N and P. Metabolomic analysis revealed that DX-9 inoculation significantly increased the soil levels of phytolaccoside A, 7,8-dihydropteroic acid, novobiocin, and azafrin. These compounds were enriched in microbe pathway metabolites, including xenobiotic biodegradation and metabolism, biosynthesis of other secondary metabolites, and metabolism of cofactors and vitamins. In summary, the use of Bacillus atrophaeus DX-9 against potato CS offers an alternative biocontrol method that can improve both soil microbial community and properties. This study provides insight into the potential mechanisms by which microbial inoculants can control CS disease.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42994-025-00199-3.PMID:40060187 | PMC:PMC11889282 | DOI:10.1007/s42994-025-00199-3

aBIOTECH. 2025 Jan 23;6(1):116-132. doi: 10.1007/s42994-024-00194-0. eCollection 2025 Mar.ABSTRACTPlant metabolites are crucial for the growth, development, environmental adaptation, and nutritional quality of plants. Plant metabolomics, a key branch of systems biology, involves the comprehensive analysis and interpretation of the composition, variation, and functions of these metabolites. Advances in technology have transformed plant metabolomics into a sophisticated process involving sample collection, metabolite extraction, high-throughput analysis, data processing, and multidimensional statistical analysis. In today's era of big data, the field is witnessing an explosion in data acquisition, offering insight into the complexity and dynamics of plant metabolism. Moreover, multiple omics strategies can be integrated to reveal interactions and regulatory networks across different molecular levels, deepening our understanding of plant biological processes. In this review, we highlight recent advances and challenges in plant metabolomics, emphasizing the roles for this technique in improving crop varieties, enhancing nutritional value, and increasing stress resistance. We also explore the scientific foundations of plant metabolomics and its applications in medicine, and ecological conservation.PMID:40060186 | PMC:PMC11889285 | DOI:10.1007/s42994-024-00194-0

J Tradit Complement Med. 2024 Nov 25;15(2):192-204. doi: 10.1016/j.jtcme.2024.11.015. eCollection 2025 Mar.ABSTRACTAtractylenolide III, a sesquiterpene extracted from the rhizome of Atractylodes macrocephala (Asteraceae), exhibits pharmacological effects, including improvement of gastrointestinal function, regulation of immune function, anti-inflammatory and antibacterial properties. Pyrotinib, a representative TKI originally developed in China, is classified as a Class 1.1 novel drug, exhibits superior efficacy compared to similar drugs. Notably, the overall incidence of pyrotinib-induced diarrhea stands at 95 %, with 40 % of cases classified as grade ≥3 diarrhea. Currently, the effect of Atractylenolide III on pyrotinib-induced diarrhea and the underlying mechanisms remain unclear. Therefore, in this study, we established a pyrotinib (80 mg/kg/day) Wistar rat diarrhea model to explore the effect of Atractylenolide III on pyrotinib-induced diarrhea. We exploded the potential mechanism of Atractylenolide III via MQAE chloride fluorescent probe, RT-qPCR, Western blot, 16S rRNA sequencing, metabolomics, etc. We found that Atractylenolide III demonstrated the ability to alleviate pyrotinib-induced diarrhea without compromising its anti-tumor effects, inhibited pyrotinib-induced chloride secretion, and the potential mechanism of action involved enhancing AMPK phosphorylation while decreasing CFTR protein expression. Additionally, Atractylenolide III alleviated pyrotinib-induced diarrhea by modulating intestinal flora structure and increasing lithocholic acid content. This study could provide potential novel traditional Chinese medicine targets for treating diarrhea caused by tyrosine kinase inhibitor drugs, such as pyrotinib. The study emphasizes the role of TCM in minimizing adverse effects during tumor treatment.PMID:40060149 | PMC:PMC11883636 | DOI:10.1016/j.jtcme.2024.11.015

Res Sq [Preprint]. 2025 Feb 27:rs.3.rs-5256734. doi: 10.21203/rs.3.rs-5256734/v1.ABSTRACTRed blood cell (RBC) transfusion, a life-saving intervention, is limited by reduced RBC potency over time. Cold storage at + 4°C for up to 42 days can reduce transfusion efficacy due to alterations termed the "storage lesion." Strategies to mitigate the storage lesion include alkaline additive solutions and supercooled storage to extend storage by reducing metabolic stresses. However, RBC metabolism during supercooled storage in standard or alkaline additives remains unstudied. This study, thus, investigated the impact of storage additives (alkaline E-Sol5 and standard SAGM) and temperatures (+ 4°C, -4°C, -8°C) on RBC metabolism during 21- and 42-days storage using high-throughput metabolomics. RBCs stored with E-Sol5 showed increased glycolysis and higher ratios of reduced to oxidized glutathione compared to SAGM. Supercooled storage at -4°C showed markedly lower hemolysis than - 8°C, preserved adenylate pools, decreased glucose consumption, and reduced lactate accumulation and pentose phosphate pathway activation. The combination of supercooled storage and E-Sol5 helped to preserve ATP and 2,3-DPG reservoirs, while preventing catabolism and free fatty acid accumulation. While supercooled storage with E-Sol5 offers a promising alternative to standard storage, preserving RBC metabolic and functional quality, further research is necessary to validate and improve on these foundational findings.​​.PMID:40060052 | PMC:PMC11888543 | DOI:10.21203/rs.3.rs-5256734/v1

Open Life Sci. 2025 Mar 7;20(1):20220996. doi: 10.1515/biol-2022-0996. eCollection 2025.ABSTRACTRubus corchorifolius, a medicinal plant of the Rosaceae family, is known for its diverse bioactive compounds. This study employs widely targeted metabolomics to investigate the metabolic profiles of leaf, stem, and flower tissue from R. corchorifolius. Using ultra-performance liquid chromatography coupled with tandem mass spectrometry, we identified 1,946 metabolites across the three tissue types. Multivariate statistical analyses revealed distinct metabolic signatures for each tissue, with flowers showing the most distinctive profile. Differential accumulation of flavonoids, phenolic acids, and primary metabolites reflected the specialised functions of each tissue type. Pathway enrichment analysis highlighted tissue-specific metabolic activities, including flavonoid biosynthesis in flowers and chlorophyll metabolism in leaves. This comprehensive metabolic characterisation provides a foundation for further investigations into the biosynthetic pathways and physiological functions of bioactive compounds in R. corchorifolius, potentially guiding future applications in medicine and agriculture.PMID:40059878 | PMC:PMC11889504 | DOI:10.1515/biol-2022-0996

JCI Insight. 2025 Mar 10;10(5):e186070. doi: 10.1172/jci.insight.186070.ABSTRACTChronic kidney diseases (CKDs) are a global health concern, necessitating a comprehensive understanding of their complex pathophysiology. This study explores the use of 2 complementary multidimensional -omics data integration methods to elucidate mechanisms of CKD progression as a proof of concept. Baseline biosamples from 37 participants with CKD in the Clinical Phenotyping and Resource Biobank Core (C-PROBE) cohort with prospective longitudinal outcome data ascertained over 5 years were used to generate molecular profiles. Tissue transcriptomic, urine and plasma proteomic, and targeted urine metabolomic profiling were integrated using 2 orthogonal multi-omics data integration approaches, one unsupervised and the other supervised. Both integration methods identified 8 urinary proteins significantly associated with long-term outcomes, which were replicated in an adjusted survival model using 94 samples from an independent validation group in the same cohort. The 2 methods also identified 3 shared enriched pathways: the complement and coagulation cascades, cytokine-cytokine receptor interaction pathway, and the JAK/STAT signaling pathway. Use of different multiscalar data integration strategies on the same data enabled identification and prioritization of disease mechanisms associated with CKD progression. Approaches like this will be invaluable with the expansion of high-dimension data in kidney diseases.PMID:40059827 | DOI:10.1172/jci.insight.186070

JCI Insight. 2025 Mar 10;10(5):e186745. doi: 10.1172/jci.insight.186745.ABSTRACTInfectious complications (ICs) in acute pancreatitis (AP) are primarily driven by intestinal bacterial translocation, significantly increasing mortality and hospital stays. Despite this, the role of the gut microenvironment, particularly its metabolic aspects, in AP remains poorly understood. In this study, we investigated a cohort of patients with AP, and conducted supplemental murine studies, to explore the relationship between the gut metabolome and the development of ICs. Metabolomic analysis revealed that disruptions in gut tryptophan metabolism - especially reductions in serotonin and indole pathways - are key features associated with IC occurrence. Additionally, elevated plasma levels of tryptophan metabolites within the kynurenine pathway were identified as valuable predictive biomarkers for ICs. Mechanistic studies in murine models demonstrated that an impaired intestinal Th17 response, modulated by these tryptophan metabolites, plays a critical role in IC development. Serotonin supplementation enhanced Th17 responses, reducing IC incidence, while administration of kynurenic acid, a kynurenine metabolite, exacerbated pancreatic infections, potentially through immunosuppressive effects. These findings highlight the pivotal role of tryptophan metabolites in AP pathogenesis, emphasizing their potential as both predictive markers and therapeutic targets in IC management.PMID:40059826 | DOI:10.1172/jci.insight.186745