PubMed

Mol Biol (Mosk). 2024 Sep-Oct;58(5):684-693.ABSTRACTVarious age-related disorders accumulate during aging, causing a decline in tissue and organ function, raising the risk of disease development, and leading to death. Age-related phenotypes are tightly related to an increase in coordinated, progressive changes in the transcriptome, proteome, metabolome, microbiome, and epigenome. Age-dependent modifications of the transcriptome, caused by changes in epigenetic, transcriptional, and post-transcriptional regulation of gene expression, lead to the accumulation of age-related changes in the proteome and metabolome. In turn, dynamic changes in the microbiota during aging also affect gene expression and thus lead to age-related changes in the proteome and metabolome. Recent studies have shown that multi-omic rejuvenation technologies decrease age-related disorders and extend longevity. For example, the short-term induction of the expression of transcription factors that ensure the reprogramming of somatic cells into pluripotent stem cells is accompanied by the restoration of the DNA methylation pattern and transcriptome expression profile characteristic of younger tissues, resulting in an increased lifespan. In this review, we discuss existing multi-omic rejuvenation technologies and the prospects for extending and improving life.PMID:39970112

Mol Biol Cell. 2025 Feb 19:mbcE25020055. doi: 10.1091/mbc.E25-02-0055. Online ahead of print.ABSTRACTAxonemal dynein assembly occurs in the cytoplasm and numerous cytosolic factors are specifically required for this process. Recently, one factor (DNAAF3/PF22) was identified as a methyltransferase. Examination of Chlamydomonas dyneins found they are methylated at sub-stoichiometric levels on multiple sites, including Lys and Arg residues in several of the nucleotide binding domains and on the microtubule-binding region. Given the highly conserved nature of axonemal dyneins, one key question is whether methylation happens only in dyneins from the chlorophyte algae, or if these modifications occur more broadly throughout the motile ciliated eukaryotes. Here we take a phyloproteomic approach and examine dynein methylation in a wide range of eukaryotic organisms bearing motile cilia. We find unambiguous evidence for methylation of axonemal dyneins in alveolates, chlorophytes, trypanosomes, and a broad range of metazoans. Intriguingly, we were unable to identify a single instance of methylation on Drosophila melanogaster sperm dyneins even though dipterans express a Dnaaf3 ortholog, or in spermatozoids of the fern Ceratopteris, which assembles inner arms but lacks both outer arm dyneins and DNAAF3. Thus, methylation of axonemal dyneins has been broadly conserved in most eukaryotic groups and has the potential to variably modify the function of these motors.PMID:39969973 | DOI:10.1091/mbc.E25-02-0055

Metab Brain Dis. 2025 Feb 19;40(3):130. doi: 10.1007/s11011-024-01451-3.ABSTRACTThis study aimed to identify metabolic footprints associated with distinct phenotypes of acute ischemic stroke (AIS) using untargeted metabolomics. We included 20 samples each from AIS phenotype A (n = 251), B (n = 213), and C (n = 43) groups, along with 20 age- and gender-matched healthy controls (HCs). Plasma metabolic profiles were analyzed using liquid chromatography-mass spectrometry (LC-MS). Weighted gene correlation network analysis (WGCNA) evaluated associations between metabolite clusters and clinical traits, including the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). We identified three, five, and six key differential metabolites for diagnosing phenotypes A, B, and C, respectively, demonstrating high diagnostic performance. These metabolites were focused on fatty acids, sex hormones, amino acids, and their derivatives. WGCNA identified 12 core metabolites involved in phenotype progression. Notably, phenylalanylphenylalanine and phenylalanylleucine were inversely correlated with disease severity and disability. Metabolites related to energy supply and inflammation were common across phenotypes, with additional changes in ionic homeostasis in phenotype A and decreased neurotransmitter release in phenotype C. Biosynthesis of unsaturated fatty acids and the pentose phosphate pathway (PPP) were relevant across all phenotypes, while the folate biosynthesis pathway was linked to phenotype C and clinical scales. Key metabolites, including phenylalanylphenylalanine and phenylalanylleucine, and pathways such as folate biosynthesis, significantly contribute to AIS severity and differentiation of phenotypes. These findings offer new insights into the pathogenesis and mechanisms underlying AIS phenotypes.PMID:39969622 | DOI:10.1007/s11011-024-01451-3

Cell Mol Life Sci. 2025 Feb 19;82(1):79. doi: 10.1007/s00018-025-05613-z.ABSTRACTIdiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial pneumonia, with increasing incidence and prevalence. One of the cellular characteristics is the differentiation of fibroblasts to myofibroblasts. However, the metabolic-related signaling pathway regulated by circular RNAs (circRNAs) during this process remains unclear. Here, we demonstrated that circ0066187 promoted fibroblast-to-myofibroblast differentiation by metabolic-related signaling pathway. Mechanism analysis research identified that circ0066187 directly targeted signal transducer and activator of transcription 3 (STAT3)-mediated metabolism signal pathway to enhance fibroblast-to-myofibroblast differentiation by sponging miR-29b-2-5p, resulting in pulmonary fibrosis. Integrative multi-omics analysis of metabolomics and proteomics revealed three pathways co-enriched in proteomics and metabolomics, namely, Protein digestion and absorption, PI3K-Akt signaling pathway, and FoxO signaling pathway. In these three signaling pathways, seven differentially expressed metabolites such as L-glutamine, L-proline, adenosine monophosphate (AMP), L-arginine, L-phenylalanine, L-lysine and L-tryptophan, and six differentially expressed proteins containing dipeptidyl peptidase-4 (DPP4), cyclin D1 (CCND1), cyclin-dependent kinase 2 (CDK2), fibroblast growth factor 2 (FGF2), collagen type VI alpha 1 (COL6A1) and superoxide dismutase 2 (SOD2) were co-enriched. Gain-and loss-of-function studies and rescue experiments were performed to verify that circ0066187 promoted STAT3 expression by inhibiting miR-29b-2-5p expression to control the above metabolites and proteins. As a result, these metabolites and proteins provided the material basis and energy requirements for the progression of pulmonary fibrosis. In conclusion, circ0066187 can function as a profibrotic metabolism-related factor, and interference with circ0066187 can prevent pulmonary fibrosis. The finding supported that circ0066187 can be a metabolism-related therapeutic target for IPF treatment.PMID:39969586 | DOI:10.1007/s00018-025-05613-z

Plant Cell Environ. 2025 Feb 19. doi: 10.1111/pce.15437. Online ahead of print.ABSTRACTLeaf senescence induced by high temperature (HT) has become a primary factor limiting maize yield, particularly during the filling stage. Exogenous salicylic acid (SA) has emerged as an effective strategy to mitigate leaf senescence and HT-induced damage, though its underlying mechanisms remain unclear. This study investigated the regulatory mechanism of SA application on waxy maize subjected to HT during the early filling stage. Compared to HT alone, exogenous SA alleviated the inhibition of photosynthesis and oxidative damage by enhancing the activities of enzymes involved in photosynthesis and antioxidant system and modulating phytohormone metabolism and signal transduction pathways, thereby reducing leaf senescence and mitigating yield loss under HT. Transcriptomic and metabolomic analyses showed that HT downregulated most genes involved in the starch and sucrose metabolism pathway in leaves but promoted soluble sugar accumulation, which represents a plant strategy to cope with HT. Conversely, exogenous SA reversed this change and further enhanced soluble sugar accumulation in leaves. SA also regulated sugar metabolism by inhibiting trehalose-6-phosphate synthesis and activating SnRK1 to resist HT. Furthermore, SA stimulated lignin biosynthesis through the phenylpropanoid pathway, ensuring cell membrane integrity under HT. The relationship between SA signalling and plant heat tolerance was validated using a maize SA synthesis-synthetic mutant.PMID:39969247 | DOI:10.1111/pce.15437

Clin Exp Immunol. 2025 Feb 19:uxaf012. doi: 10.1093/cei/uxaf012. Online ahead of print.ABSTRACTNeutrophils are key effector leukocytes of the innate immune system and play a pivotal role in defending the host against microbial infections. Recent studies have identified a crucial link between glycolysis and neutrophil cellular functions. Using human neutrophils, we have investigated the intricate relationship between glycolysis, extracellular glucose availability, and the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), in the regulation of reactive oxygen species (ROS) and neutrophil extracellular trap (NET) production. We have identified that PFKFB3 is elevated in rheumatoid arthritis (RA) neutrophils and that the small molecule PFKFB3 inhibitor 3PO is a key regulator of neutrophil ROS and NET production. 3PO blocked the production of ROS and NETs in a dose-dependent manner in both RA and healthy (HC) neutrophils (p<0.01), and RA neutrophils were more sensitive to lower concentrations of 3PO. Bacterial killing was only partially inhibited by 3PO, and the proportion of live neutrophils after 24h incubation was unchanged. Using NMR metabolomics, we identified that 3PO increases the concentration of lactate, phenylalanine and L-glutamine in neutrophils, as well as significantly decreasing intracellular glutathione (adj. p-value<0.05). We also demonstrated that RA neutrophils produce ROS and NETs in culture conditions which mimic the low glucose environments encountered in RA synovial joints. Our results also suggest 3PO may have molecular targets beyond PFKFB3. By dissecting the intricate interplay between metabolism and neutrophil effector functions, this study advances the understanding of the molecular mechanisms governing pro-inflammatory neutrophil responses and identifies 3PO as a potential therapeutic for conditions characterized by dysregulated neutrophil activation.PMID:39969221 | DOI:10.1093/cei/uxaf012

Dermatol Reports. 2024 Nov 27. doi: 10.4081/dr.2024.10079. Online ahead of print.ABSTRACTLichen sclerosus (LS) is a chronic scleroatrophic dermatosis of unknown etiology that usually affects the anogenital area and occasionally the extragenital sites, which has no definitive cure. LS patients are at higher risk of developing squamous cell carcinoma (SCC) in their lifetime compared to the general population. Through a retrospective study, we evaluated the impact of regenerative medicinebased therapies on SCC onset in the context of genital LS. LS patients treated in our institute from March 2013 to December 2022 were reviewed. A total of 319 patients, including 34 treated with adipose-derived stem cells (ADSCs) graft, 31 treated with ADSCs graft and PRP, and 254 treated with platelet-rich plasma (PRP) were identified. In parallel, data extracted from the histologic institutional database searching for SCC in the anogenital area were matched to surgical records. None of the 319 LS patients developed skin SCC in the anogenital area. Our data suggest that cellular and acellular therapies achieving therapeutic control prevent continuous tissue remodeling and its evolution and, therefore, neoplastic degeneration. Regenerative approaches are considered a valid strategy for treating LS patients symptomatic despite prolonged first-line medical treatment. Studying genital carcinogenesis of LS cases, we reported for the first time a protective role of PRP, ADSCs, and combined therapies. Thus, in terms of cancer prevention, we propose that regenerative therapies ameliorating disease control of non-responders to conventional therapy represent an important innovative tool.PMID:39969047 | DOI:10.4081/dr.2024.10079

Biomed Chromatogr. 2025 Apr;39(4):e70020. doi: 10.1002/bmc.70020.ABSTRACTDalbergia hancei Benth (D. hancei) is a plant belonging to the Fabaceae family. It has analgesic and anti-inflammatory effects and is used by the Zhuang people to relieve pain. However, the mechanism underlying its analgesic effects remains unclear. This study investigates the analgesic effect of D. hancei based on metabolomics to explain the mechanism of its analgesia from a metabolomics perspective. The analgesic effect was evaluated through the acetic acid-induced writhing test and hot plate test. Three treatment groups received different dosages of D. hancei (0.91 g/kg, 3.64 g/kg, 7.28 g/kg). Its analgesic mechanism was investigated using analgesic behavioral tests and metabolomics. The results of analgesic behavioral experiments showed that all dose groups of D. hancei could relieve pain. A total of eight differential metabolites were identified in the metabolomics results. These biomarkers are associated with five metabolic pathways. Following treatment with D. hancei, eight differential metabolites were identified as regulated, primarily affecting amino acid metabolism, pantothenate and CoA biosynthesis, and steroid hormone biosynthesis. This study revealed the mechanism of analgesia from a metabolomic perspective to provide a basis for screening TCM drugs in pain treatment.PMID:39968938 | DOI:10.1002/bmc.70020

J Sep Sci. 2025 Feb;48(2):e70099. doi: 10.1002/jssc.70099.ABSTRACTMetabolomics, a powerful discipline within systems biology, aims at comprehensive profiling of small molecules in biological samples. The challenges of biological sample complexity are addressed through innovative sample preparation methods, including solid-phase extraction and microextraction techniques, enhancing the detection and quantification of low-abundance metabolites. Advances in chromatographic separation, particularly liquid chromatography (LC) and gas chromatography (GC), coupled with high-resolution (HR) mass spectrometry (MS), have significantly improved the sensitivity, selectivity, and throughput of metabolomic studies. Cutting-edge techniques, such as ion-mobility mass spectrometry (IM-MS) and tandem MS (MS/MS), further expand the capacity for comprehensive metabolite profiling. These advanced analytical platforms each offer unique advantages for metabolomics, with continued technological improvements driving deeper insights into metabolic pathways and biomarker discovery. By providing a detailed overview of current trends and techniques, this review aims to offer valuable insights into the future of metabolomics in human health research and its translational potential in clinical settings. Toward the end, this review also highlights the biomedical applications of metabolomics, emphasizing its role in biomarker discovery, disease diagnostics, personalized medicine, and drug development.PMID:39968702 | DOI:10.1002/jssc.70099

Curr Opin Endocrinol Diabetes Obes. 2025 Feb 20. doi: 10.1097/MED.0000000000000905. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: To provide an update of recent studies exploring the role of the gut microbiota and diet in the pathogenesis and treatment of irritable bowel syndrome (IBS).RECENT FINDINGS: The human gut microbiome has been recognized as an important, active source of signaling molecules that explain in part the disorder of the gut brain interaction (DGBI) in IBS. Subsequent changes in the metabolome such as the production of short-chain fatty acids (SCFA) and serotonin are associated with IBS symptoms. Dietary components are recognized as important triggers of IBS symptoms and a diet low in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) has been shown effective and safe, even when used long-term. Fecal microbiota transplantation (FMT) in IBS has not shown sustained and effective IBS symptom reduction in controlled clinical trials.SUMMARY: This update elucidates recent developments in IBS as it relates to clinical trial results targeting dietary and gut microbiota interventions. The gut microbiome is metabolically active and affects the bi-directional signaling of the gut-brain axis.PMID:39968682 | DOI:10.1097/MED.0000000000000905

Am J Reprod Immunol. 2025 Feb;93(2):e70058. doi: 10.1111/aji.70058.ABSTRACTPROBLEM: Aging is characterized by a general dysregulation of systemic immune responses that increases susceptibility to infections and malignancies. Immune cells in the female genital tract (FGT) are regulated by sex hormones, but little is known about the impact of aging and menopause on immunology in the FGT.METHOD OF STUDY: This study conducted an age-focused sub-analysis of cervicovaginal samples collected from 47 women enrolled in the Vaginal Mucosal Systems study in Winnipeg, Canada. Paired cervicovaginal lavage and cervical cytobrush were collected and analyzed by Luminex cytokine array, mass spectrometry based metaproteomics, metabolomics, and high dimensional flow cytometry.RESULTS: The median age of study participants was 38 (range 19-88), with 12 over the age of 50. Increasing age was significantly correlated with increased cervicovaginal inflammation, including inflammatory cytokine MIP-1β (r = 0.335, p = 0.023), and activated T cells (CD4+HLA-DR+ r = 0406, p = 0.009; CD8+HLA-DR+ r = 0.399, p = 0.010; CD8+CD38+HLA-DR+ r = 0.386, p = 0.013). Proteomic analysis of cervicovaginal mucus identified 925 human proteins, with 108 (11.7%) significantly correlated with age. Pathway analysis indicated biofunctions related to immune response, migration, and myeloid cell phagocytosis increased with age. Interestingly, neutrophil related pathways decreased with age, including G-CSF (r = -0.396, p = 0.006) and reactive oxygen species (z-score = -2.607, p = 2.31E-4). Vaginal Lactobacillus crispatus, a species associated with mucosal health, significantly decreased with age (r = -0.340, p = 0.022), with participants over the age of 50 more likely to have non-Lactobacillus dominant microbiomes compared to those under 40.CONCLUSIONS: Together, our data suggests that there is an increase in cervicovaginal inflammation and a decrease in L. crispatus that occurs with aging.PMID:39968674 | DOI:10.1111/aji.70058

Proc Biol Sci. 2025 Feb;292(2041):20242482. doi: 10.1098/rspb.2024.2482. Epub 2025 Feb 19.ABSTRACTLand-use change may drive viral spillover from bats into humans, partly through dietary shifts caused by decreased availability of native foods and increased availability of cultivated foods. We experimentally manipulated diets of Jamaican fruit bats to investigate whether diet influences viral shedding. To reflect dietary changes experienced by wild bats during periods of nutritional stress, Jamaican fruit bats were fed either a standard diet or a putative suboptimal diet, which was deprived of protein (suboptimal-sugar diet) and/or supplemented with fat (suboptimal-fat diet). Upon H18N11 influenza A-virus infection, bats fed on the suboptimal-sugar diet shed the most viral RNA for the longest period, but bats fed the suboptimal-fat diet shed the least viral RNA for the shortest period. Bats on both suboptimal diets ate more food than the standard diet, suggesting nutritional changes may alter foraging behaviour. This study serves as an initial step in understanding whether and how dietary shifts may influence viral dynamics in bats, which alters the risk of spillover to humans.PMID:39968620 | DOI:10.1098/rspb.2024.2482

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2025 Jan;37(1):81-86. doi: 10.3760/cma.j.cn121430-20240927-00809.ABSTRACTAcute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar and interstitial edema caused by damage to alveolar-capillary and epithelial cells, often induced by infection, sepsis, trauma, and other factors. It is marked by progressive hypoxemia and respiratory distress. Due to the diverse causes of ARDS, the unclear pathogenesis, and the absence of effective predictive markers or biomarkers, there are no effective treatment measures available, resulting in a high mortality rate. ARDS is increasingly recognized for its heterogeneity, biomarkers, and the emergence of new opportunities for the development of diagnostic tools and personalized treatment strategies provided by omics technologies. A single omics analysis cannot fully reveal the heterogeneity and complexity of ARDS, while multi-omics analysis can provide a more systematic and comprehensive understanding of ARDS. Using clinical samples is closer to the actual disease situation compared to animal models. Multi-omics studies based on clinical samples have achieved significant progress in elucidating the pathophysiology of ARDS, identifying ARDS subtypes, and identifying biomarkers related to ARDS. This review focuses on the current applications of genomics, transcriptomics, metabolomics, and proteomics analyses based on clinical samples in the ARDS field, with a focus on the application of these omics methods in ARDS heterogeneity, potential biomarkers, and pathogenesis. It also introduces the differences in the application of different clinical samples in ARDS omics research, in order to gain a deeper and more comprehensive understanding of the pathogenesis of ARDS and explore new strategies for its prevention and treatment.PMID:39968593 | DOI:10.3760/cma.j.cn121430-20240927-00809

MedComm (2020). 2025 Feb 17;6(3):e70100. doi: 10.1002/mco2.70100. eCollection 2025 Mar.ABSTRACTChemotherapy combined with checkpoint blockade antibodies targeting programmed cell death protein (PD-1) has achieved remarkable success in non-small cell lung cancer. However, few patients benefit from long-term treatment. Therefore, biomarkers capable of guiding the optimal therapeutic selection and reducing unnecessary toxicity are of pressing importance. In our research, we gathered serial blood samples from two groups of non-small cell lung cancer patients: 49 patients received a combination of therapies, and 34 patients went under chemotherapy alone. Utilizing non-targeted metabolomic analysis, we examined different metabolites' disparity. Among the lot, L-phenylalanine emerged as a significant prognostic marker in the combination treatment of non-small cell lung cancer patients, interestingly absent in patients under sole chemotherapy. The reduced ratio of L-phenylalanine concentration (two-cycle treatment vs. pre-treatment) was associated with improved progression-free survival (hazard ratio = 1.8000, 95% confidence interval: 0.8566‒3.7820, p < 0.0001) and overall survival (hazard ratio = 1.583, 95% confidence interval: 0.7416‒3.3800, p < 0.005). We further recruited two validation cohorts (cohort 1: 40 patients and cohort 2: 30 patients) to validate the sensitivity and specificity of L-phenylalanine prediction. Our results demonstrate that a model based on L-phenylalanine variations could serve as an early risk-assessment tool for non-small cell lung cancer patients undergoing treatment, potentially facilitating strategic clinical decision-making.PMID:39968502 | PMC:PMC11832432 | DOI:10.1002/mco2.70100

MedComm (2020). 2025 Feb 17;6(3):e70104. doi: 10.1002/mco2.70104. eCollection 2025 Mar.ABSTRACTCompelling evidence supports a link between early-life gut microbiota and the metabolic outcomes in later life. Using an early-life antibiotic exposure model in BALB/c mice, we investigated the life-course impact of prenatal and/or postnatal antibiotic exposures on the gut microbiome of offspring and the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Compared to prenatal antibiotic exposure alone, postnatal antibiotic exposure more profoundly affected gut microbiota development and succession, which led to aggravated endotoxemia and metabolic dysfunctions. This was primarily resulted from the overblooming of gut Parabacteroides and hepatic accumulation of cytotoxic lysophosphatidyl cholines (LPCs), which acted in conjunction with LPS derived from Parabacteroides distasonis (LPS_PA) to induce cholesterol metabolic dysregulations, endoplasmic reticulum (ER) stress and apoptosis. Integrated serum metabolomics, hepatic lipidomics and transcriptomics revealed enhanced glycerophospholipid hydrolysis and LPC production in association with the upregulation of PLA2G10, the gene controlling the expression of the group X secretory Phospholipase A2s (sPLA2-X). Taken together, our results show microbial modulations on the systemic MASLD pathogenesis and hepatocellular lipotoxicity pathways following early-life antibiotic exposure, hence help inform refined clinical practices to avoid any prolonged maternal antibiotic administration in early life and potential gut microbiota-targeted intervention strategies.PMID:39968496 | PMC:PMC11832435 | DOI:10.1002/mco2.70104

Front Pharmacol. 2025 Feb 4;16:1536438. doi: 10.3389/fphar.2025.1536438. eCollection 2025.ABSTRACTPharmaceuticals such as selective serotonin reuptake inhibitors (SSRIs), are increasingly detected in aquatic environments, posing potential risks to non-target organisms, because many of those substances are widely shared neuromodulator. In this study, we investigated the effects of SSRI antidepressant, namely, fluoxetine, exposure on the freshwater snail L. stagnalis, focusing on egg development, neurochemical pathways, and lipid metabolism. Snails were exposed to a range of 51-434 µg fluoxetine L⁻1 for 7 days, followed by analysis of survival, feeding behaviour, reproduction, and metabolomic changes in the central nervous system (CNS), albumen gland, and eggs. Although no significant effects were observed on survival or fecundity, fluoxetine exposure significantly impaired egg development in a dose-dependent manner, reducing hatching rates with an EC50 of 126 µg fluoxetine L⁻1. Removal of eggs from the contaminated environment partially reversed these developmental effects, suggesting potential recovery if fluoxetine levels decrease. Molecular analysis revealed several neurochemical and lipidomic alterations. In the CNS, elevated levels of catecholamines, phosphatidylcholines (PC), and ceramides were linked to disruptions in neurotransmission, membrane integrity, and impaired embryo development. In the albumen gland, we detected a decrease of key lipid classes, including sphingomyelins and fatty acids, which can be linked with impaired egg quality. Additionally, a decrease in histamine in both the albumen gland and eggs suggested further disruption of egg development, potentially affecting metamorphosis success. Moreover, the dose-dependent increase in choline, along with PC and oxidized PC, indicated oxidative stress and lipid peroxidation in the CNS and exposed eggs of Lymnaea stagnalis. Our findings highlight the benefits of combining behavioral assessments with metabolomic profiling to better understand the mechanistic pathways underlying fluoxetine's adverse effects.PMID:39968180 | PMC:PMC11832466 | DOI:10.3389/fphar.2025.1536438

Endocr Oncol. 2025 Feb 11;5(1):e240072. doi: 10.1530/EO-24-0072. eCollection 2025 Jan.ABSTRACTRadioactive iodine (RAI) treatment is an established therapeutic tool for 'differentiated thyroid cancers'. The therapeutic effectiveness is linked to the preservation of the iodine-concentrating ability of the neoplastic tissue, a unique, inherent quality of a normal thyroid gland. Iodine concentration is a function involving the expression of transport proteins and organification. Thyroid differentiation score (TDS) is an integrated quantity, first introduced by The Cancer Genome Atlas (TCGA), conveying the relative expression of proteins involved in histogenesis, morphologic and functional differentiation of thyroid tissue. The concept is well described for the expression of metabolic suppression of thyroid cancers associated with RAI-refractoriness. We evaluated the mRNA expressions of thyroid metabolomics-specific genes, comparing normal thyroid to neoplastic tissue in a cohort where patient-specific paired data were available. Fifty-nine papillary thyroid cancer samples from the TCGA project with matched tumor-normal tissue samples were analyzed. Of the 59 samples, 29 contained a BRAFV600E mutation, seven a RAS mutation, 10 a mutation other than BRAF or RAS, and 14 either no mutation or an unknown mutation. Our analysis demonstrated that there was a significant downregulation of the RAI theranostic transcriptome, much more significant in BRAF-initiated cancers vs RAS-initiated ones. There was also notable heterogeneity in respective mutational categories where individual assessment of the thyroid differentiation profile (TDP) would potentially be clinically relevant for RAI treatment planning. Determination of TDP and development of a theranostic TDS may have an impact on clinical decision making as to the extent of thyroidectomy and postoperative RAI therapy.PMID:39968056 | PMC:PMC11834997 | DOI:10.1530/EO-24-0072

Food Chem X. 2025 Jan 27;25:102234. doi: 10.1016/j.fochx.2025.102234. eCollection 2025 Jan.ABSTRACTNatural storage promotes raw Pu-erh tea (RaPT) aging along with chemical conversion and flavor evolution. In this study, quantitative descriptive analysis (QDA) and UHPLC-Orbitrap-MS/MS-based non-targeted metabolomics were performed to illustrate dynamic changes of taste compounds across 18 RaPT samples during the storage. Multivariate statistical analyses effectively classified stored RaPT into three groups based on storage stages, confirming that storage duration, rather than environmental conditions, primarily influences the taste profile and the changes in non-volatile compounds. A total of 509 characteristic metabolites (VIP > 1.0, P < 0.05, and FC > 1.50 or < 0.67) including multifarious flavor compounds related to tastes evolution were identified. Notable changes included the reduction, transformation, and condensation of flavonoids (such as catechins, flavonol glycosides, and anthocyanins) and amino acids, alongside an accumulation of organic acids, catechin/amino acid derivatives, flavoalkaloids, and gallic acid. These transformations generated significantly (P < 0.05) decreased umami, bitterness, and astringency, while significantly (P < 0.05) increasing sourness and kokumi. Molecular docking analyses further revealed that certain compounds, notably puerins and N-ethyl-2-pyrrolidone-substituted flavan-3-ols (EPSFs), exhibit high binding affinities with CaSR and OTOP1, contributing to the kokumi and sourness taste profiles.PMID:39968040 | PMC:PMC11833447 | DOI:10.1016/j.fochx.2025.102234

Front Cell Infect Microbiol. 2025 Feb 4;15:1557057. doi: 10.3389/fcimb.2025.1557057. eCollection 2025.NO ABSTRACTPMID:39967790 | PMC:PMC11832537 | DOI:10.3389/fcimb.2025.1557057

Front Microbiol. 2025 Feb 4;16:1520459. doi: 10.3389/fmicb.2025.1520459. eCollection 2025.ABSTRACTINTRODUCTION: Phosphorus (P) is a crucial growth-limiting nutrient in soil, much of which remains challenging for plants to absorb and use. Unlike chemical phosphate fertilizers, phosphate-solubilizing microorganisms (PSMs) offer a means to address available phosphorus deficiency without causing environmental harm. PSMs possess multiple mechanisms for phosphorus solubilization. Although the phosphorus-solubilizing mechanisms of phosphate-solubilizing bacteria (PSB) have been well characterized, the mechanisms utilized by phosphate-solubilizing fungi (PSF) remain largely unexplored.METHODS: This study isolated a PSF strain, Trametes gibbosa T-41, from soil and evaluated its phosphorus solubilizing capacity with organic (calcium phytin; Phytin-P) and inorganic (tricalcium phosphate; Ca-P) phosphorus sources. The phosphorus solubilization, enzyme activity, and organic acid production of T-41 were measured. And the P-solubilizing mechanism conducted by transcriptomic and metabolomic analyses.RESULTS AND DISCUSSION: T-41 exhibited varying phosphorus solubilizing capacity when grown with organic (calcium phytin; Phytin-P) and inorganic (tricalcium phosphate; Ca-P) phosphorus sources (109.80 ± 8.9 mg/L vs. 57.5 ± 7.9 mg/L, p < 0.05). Compared with the Ca-P treatment, T-41 demonstrated a stronger alkaline phosphatase (ALP) production capacity under Phytin-P treatment (34.5 ± 1.2 μmol/L/h vs. 19.8 ± 0.8 μmol/L/h, p < 0.05). Meanwhile, the production of oxalic acid, maleic acid, and succinic acid was higher under Phytin-P treatment (p < 0.05). Transcriptomic and metabolomic analysis revealed that different phosphorus sources altered metabolic pathways such as galactose metabolism, glyoxylate and dicarboxylic acid metabolism, and ascorbate and aldolate metabolism. Key metabolites like myo-inositol, 2-oxoglutarate, and pyruvate were found to impact the performance of T. gibbosa T-41 differently under the two P sources. Notably, synthesis in Ca-P vs. Pytin-P, T-41 upregulated genes involved in myo-inositol synthesis, potentially enhancing its P-solubilizing ability. These results provide new insights into the molecular mechanisms of PSF at the transcriptomic and metabolomic levels, laying a theoretical foundation for the broader application of PSF as bio-phosphorus fertilizers in the future.PMID:39967735 | PMC:PMC11832667 | DOI:10.3389/fmicb.2025.1520459