PubMed

Arq Bras Cir Dig. 2025 Feb 28;38:e1870. doi: 10.1590/0102-6720202500001e1870. eCollection 2025.ABSTRACTBACKGROUND: Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), lacks a known etiology. Although clinical symptoms, imaging, and colonoscopy are common diagnostic tools, fecal calprotectin (FC) serves as a widely used biomarker to track disease activity. Metabolomics, within the omics sciences, holds promise for identifying disease progression biomarkers. This approach involves studying metabolites in biological media to uncover pathological factors.AIMS: The purpose of this study was to explore fecal metabolomics in IBD patients, evaluate its potential in differentiating subtypes, and assess disease activity using FC.METHODS: Cross-sectional study including IBD patients, clinical data, and FC measurements (=200 μg/g as an indicator of active disease).RESULTS: Fecal metabolomics utilized chromatography mass spectrometry/solid phase microextraction with MetaboAnalyst 5.0 software for analysis. Of 52 patients (29 UC, 23 CD), 36 (69.2%) exhibited inflammatory activity. We identified 56 fecal metabolites, with hexadecanoic acid, squalene, and octadecanoic acid notably distinguishing CD from UC. For UC, octadecanoic and hexadecanoic acids correlated with disease activity, whereas octadecanoic acid was most relevant in CD.CONCLUSIONS: These findings highlight the potential of metabolomics as a noninvasive complement for evaluating IBD, aiding diagnosis, and assessing disease activity.PMID:40052996 | DOI:10.1590/0102-6720202500001e1870

J Clin Endocrinol Metab. 2025 Feb 10:dgaf081. doi: 10.1210/clinem/dgaf081. Online ahead of print.ABSTRACTCONTEXT: Primary aldosteronism (PA) is commonly caused by somatic mutations of CACNA1D encoding Cav1.3, one of the four L-type calcium channels. The over-the-counter drug, cinnarizine, fits the Cav1.3 crystal structure pore domain.OBJECTIVE: We hypothesized that Cav1.3 blockade by cinnarizine may achieve similar, or greater, reduction in aldosterone secretion than nonselective Cav1.2/1.3 blockade by nifedipine.METHODS: Separate wells of angiotensin II-stimulated HAC15 cells were treated with either cinnarizine (1-30 μM) or nifedipine (1-100 μM). Aldosterone concentrations were measured in culture medium; RNA extraction and quantitative polymerase chain reaction were performed to evaluate CYP11B2 expression. A prospective, open-label, crossover study was conducted of 15 adults with PA, treated with 2 weeks of cinnarizine 30 mg 3 times a day or nifedipine extended release 60 mg daily, separated by a 2-week washout. The hierarchical primary outcome was change in aldosterone-to-renin ratio (ARR), urinary tetrahydroaldosterone (THA), and plasma aldosterone concentration (PAC). Blood pressure change was a secondary outcome. Parametric analysis was undertaken on log-transformed data. (ClinicalTrials.gov: NCT05686993).RESULTS: Both drugs reduced aldosterone concentrations and CYP11B2 expression in vitro. Mean changes ± SEM in fold change of aldosterone concentrations and CYP11B2 were -0.47 ± 0.05 and -0.56 ± 0.07, respectively, with cinnarizine 30 μM and -0.59 ± 0.05 and -0.78 ± 0.07 with nifedipine 100 μM. In the clinical crossover trial, ARR was reduced by nifedipine but not cinnarizine (F = 3.25; P = .047); PAC rose with both drugs (F = 4.77; P = .013), but urinary THA was unchanged.CONCLUSION: A Cav1.3 ligand, cinnarizine, reduced aldosterone secretion from adrenocortical cells, but at maximum-soluble concentrations was less effective than the nonselective calcium blocker, nifedipine. At clinical doses, cinnarizine did not reduce plasma ARR in patients with PA, and, as in vitro, was inferior to nifedipine. The limited efficacy of high-dose nifedipine may be due to incomplete Cav1.3 blockade, or to a role for non-L-type calcium channels in aldosterone secretion.PMID:40052842 | DOI:10.1210/clinem/dgaf081

FASEB J. 2025 Mar 15;39(5):e70411. doi: 10.1096/fj.202402726R.ABSTRACTViral infections can cause cellular dysregulation of metabolic reactions. Viruses alter host metabolism to meet their replication needs. The impact of viruses on specific metabolic pathways is not well understood, even in well-studied viruses, such as human adenovirus. Adenoviral infection is known to influence cellular glycolysis and respiration; however, global effects on overall cellular metabolism in response to infection are unclear. Furthermore, few studies have employed an untargeted approach, combining emphasis on viral dosage and infection. To address this, we employed untargeted metabolomics to quantify the dynamic metabolic shifts in fibroblasts infected with human adenovirus serotype 5 (HAdV-5) at three dosages (0.5, 1.0, and 2.0 multiplicity of infection [MOI]) and across 4 time points (6-, 12-, 24-, and 36-h post-infection [HPI]). The greatest differences in individual metabolites were observed at 6- and 12-h post-infection, correlating with the early phase of the HAdV-5 infection cycle. In addition to its effects on glycolysis and respiration, adenoviral infection downregulates cysteine and unsaturated fatty acid metabolism while upregulating aspects of purine metabolism. These results reveal specific metabolic pathways dysregulated by adenoviral infection and the associated dynamic shifts in metabolism, suggesting that viral infections alter energetics via profound changes in lipid, nucleic acid, and protein metabolism. The results revealed previously unconsidered metabolic pathways disrupted by HAdV-5 that can alter cellular metabolism, thereby prompting further investigation into HAdV mechanisms and antiviral targeting.PMID:40052831 | DOI:10.1096/fj.202402726R

Elife. 2025 Mar 7;13:RP102205. doi: 10.7554/eLife.102205.ABSTRACTThe most common primary malignancy of the liver, hepatocellular carcinoma (HCC), is a heterogeneous tumor entity with high metastatic potential and complex pathophysiology. Increasing evidence suggests that tissue mechanics plays a critical role in tumor onset and progression. Here, we show that plectin, a major cytoskeletal crosslinker protein, plays a crucial role in mechanical homeostasis and mechanosensitive oncogenic signaling that drives hepatocarcinogenesis. Our expression analyses revealed elevated plectin levels in liver tumors, which correlated with poor prognosis for HCC patients. Using autochthonous and orthotopic mouse models we demonstrated that genetic and pharmacological inactivation of plectin potently suppressed the initiation and growth of HCC. Moreover, plectin targeting potently inhibited the invasion potential of human HCC cells and reduced their metastatic outgrowth in the lung. Proteomic and phosphoproteomic profiling linked plectin-dependent disruption of cytoskeletal networks to attenuation of oncogenic FAK, MAPK/Erk, and PI3K/Akt signatures. Importantly, by combining cell line-based and murine HCC models, we show that plectin inhibitor plecstatin-1 (PST) is well-tolerated and potently inhibits HCC progression. In conclusion, our study demonstrates that plectin-controlled cytoarchitecture is a key determinant of HCC development and suggests that pharmacologically induced disruption of mechanical homeostasis may represent a new therapeutic strategy for HCC treatment.PMID:40052672 | DOI:10.7554/eLife.102205

Compr Rev Food Sci Food Saf. 2025 Mar;24(2):e70156. doi: 10.1111/1541-4337.70156.ABSTRACTPlant-derived polysaccharides have emerged as sustainable biopolymers for fabricating nanoparticles (polysaccharide-based nanomaterials [PS-NPs]), presenting unique opportunities to enhance food functionality and human health. PS-NPs exhibit exceptional biocompatibility, biodegradability, and structural versatility, enabling their integration into functional foods to positively influence gut microbiota. This review explores the mechanisms of PS-NPs interaction with gut microbiota, highlighting their ability to promote beneficial microbial populations, such as Lactobacilli and Bifidobacteria, and stimulate the production of short-chain fatty acids. Key synthesis and stabilization methods of PS-NPs are discussed, focusing on their role in improving bioavailability, stability, and gastrointestinal delivery of bioactive compounds in food systems. The potential of PS-NPs to address challenges in food science, including enhancing nutrient absorption, mitigating intestinal dysbiosis, and supporting sustainable food production through innovative nanotechnology, is critically evaluated. Barriers such as enzymatic degradation and physicochemical stability are analyzed, alongside strategies to optimize their functionality within complex food matrices. The integration of PS-NPs in food systems offers a novel approach to modulate gut microbiota, improve intestinal health, and drive the development of next-generation functional foods. Future research should focus on bridging knowledge gaps in metagenomic and metabolomic profiling of PS-NPs, optimizing their design for diverse applications, and advancing their role in sustainable and health-promoting food innovations.PMID:40052474 | DOI:10.1111/1541-4337.70156

Plant J. 2025 Mar;121(5):e70086. doi: 10.1111/tpj.70086.ABSTRACTPlant specialized metabolites play key roles in diverse physiological processes and ecological interactions. Identifying structurally novel metabolites, as well as discovering known compounds in new species, is often crucial for answering broader biological questions. The Piper genus (Piperaceae family) is known for its special phytochemistry and has been extensively studied over the past decades. Here, we investigated the alkaloid diversity of Piper fimbriulatum, a myrmecophytic plant native to Central America, using a metabolomics workflow that combines untargeted LC-MS/MS analysis with a range of recently developed computational tools. Specifically, we leverage open MS/MS spectral libraries and metabolomics data repositories for metabolite annotation, guiding isolation efforts toward structurally new compounds (i.e., dereplication). As a result, we identified several alkaloids belonging to five different classes and isolated one novel seco-benzylisoquinoline alkaloid featuring a linear quaternary amine moiety which we named fimbriulatumine. Notably, many of the identified compounds were never reported in Piperaceae plants. Our findings expand the known alkaloid diversity of this family and demonstrate the value of revisiting well-studied plant families using state-of-the-art computational metabolomics workflows to uncover previously overlooked chemodiversity. To contextualize our findings within a broader biological context, we employed a workflow for automated mining of literature reports of the identified alkaloid scaffolds and mapped the results onto the angiosperm tree of life. By doing so, we highlight the remarkable alkaloid diversity within the Piper genus and provide a framework for generating hypotheses on the biosynthetic evolution of these specialized metabolites. Many of the computational tools and data resources used in this study remain underutilized within the plant science community. This manuscript demonstrates their potential through a practical application and aims to promote broader accessibility to untargeted metabolomics approaches.PMID:40052447 | DOI:10.1111/tpj.70086

Front Plant Sci. 2025 Feb 20;15:1425154. doi: 10.3389/fpls.2024.1425154. eCollection 2024.ABSTRACTTop removal is a widely utilized method in production process of tobacco, but little is known regarding the way it impacts protein and metabolic regulation. In this study, we investigated the underlying processes of alterations in cigar tobacco leaves with and without top removal, using a combined proteomic and metabolomic approach. The results revealed that: (1) Topping significantly affected superoxide anion (O2 -) levels, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content, (2) In the cigar tobacco proteome, 385 differentially expressed proteins (DEPs) were identified, with 228 proteins upregulated and 156 downregulated. Key pathways enriched included flavonoid biosynthesis, porphyrin and chlorophyll metabolism, cysteine and methionine metabolism, and amino acid biosynthesis and metabolism. A network of 161 nodes interconnected by 102 significantly altered proteins was established, (3) In the cigar tobacco metabolome, 247 significantly different metabolites (DEMs) were identified, with 120 upregulated and 128 downregulated metabolites, mainly comprising lipids and lipid-like molecules, phenylpropanoids and polyketides, organic acids and derivatives, and organic heterocyclic compounds, (4) KEGG pathway enrichment revealed upregulation of proteins such as chalcone synthase (CHS), chalcone isomerase (CHI), naringenin 3-dioxygenase (F3H), and flavonoid 3'-monooxygenase (F3'H), along with metabolites like pinocembrin, kaempferol, trifolin, rutin, and quercetin, enhancing the pathways of 'flavonoid' and 'flavone and flavonol' biosynthesis. This study sheds light on the metabolic and proteomic responses of cigar tobacco after topping.PMID:40052119 | PMC:PMC11882365 | DOI:10.3389/fpls.2024.1425154

IMA Fungus. 2025 Feb 17;16:e141036. doi: 10.3897/imafungus.16.141036. eCollection 2025.ABSTRACTAstertataricus is a plant used in Traditional Chinese Medicine. From its roots, we isolated four endophytic fungi strains. After mass spectrometry analysis and subsequent molecular networking and dereplication, one of the strain's extracts showed a cluster of yet undescribed natural products. Additionally, the extract was found to be lethal for the nematode Caenorhabditiselegans and cytotoxic against eukaryotic cell lines. The fungal strain was characterized by morphological and molecular studies, allowing its description as a new species in the genus Tengochaeta (Chaetomiaceae), Tengochaetabulbillosa. After cultivation and extraction of the strain, the major secondary metabolites were isolated. Structure elucidation based on nuclear magnetic resonance spectroscopy and high-resolution tandem mass spectrometry revealed these compounds to be five new azaphilones. Additionally, the localization of these azaphilones in the host plant was studied by mass spectrometry imaging of different plant tissues, revealing that they were mainly localized in the aerial parts of the plant. The main compound, bulbillosin A, was evaluated for its activity against sixty cancer cell lines, revealing a differential cytotoxicity profile.PMID:40052077 | PMC:PMC11882021 | DOI:10.3897/imafungus.16.141036

Front Mol Neurosci. 2025 Feb 20;18:1548255. doi: 10.3389/fnmol.2025.1548255. eCollection 2025.ABSTRACTMitochondrial integrity is fundamental to cellular function, upheld by a network of proteases that regulate proteostasis and mitochondrial dynamics. Among these proteases, AFG3L2 is critical due to its roles in maintaining mitochondrial homeostasis, regulating mitochondrial protein quality, and facilitating mitochondrial biogenesis. Mutations in AFG3L2 are implicated in a spectrum of diseases, including spinocerebellar ataxia type 28 (SCA28) and spastic ataxia 5 (SPAX5), as well as other systemic conditions. This study employs a multi-omics approach to investigate the biochemical impact of AFG3L2 mutations in immortalized lymphoblastoid cell lines derived from a patient with biallelic variants leading to spastic ataxia (SPAX5). Our proteomic analysis revealed AFG3L2 impairment, with significant dysregulation of proteins critical for mitochondrial function, cytoskeletal integrity, and cellular metabolism. Specifically, disruptions were observed in mitochondrial dynamics and calcium homeostasis, alongside downregulation of key proteins like COX11, a copper chaperone for complex IV assembly, and NFU1, an iron-sulfur cluster protein linked to spastic paraparesis and infection-related worsening. Lipidomic analysis highlighted substantial alterations in lipid composition, with significant decreases in sphingomyelins, phosphatidylethanolamine, and phosphatidylcholine, reflecting disruptions in lipid metabolism and membrane integrity. Metabolomic profiling did not reveal any significant findings. Our comprehensive investigation into loss of functional AFG3L2 elucidates a pathophysiology extending beyond mitochondrial proteostasis, implicating a wide array of cellular processes. The findings reveal substantial cellular disturbances at multiple levels, contributing to neurodegeneration through disrupted mitochondrial respiratory chain, calcium homeostasis, cytoskeletal integrity, and altered lipid homeostasis. This study underscores the complexity of SPAX5 pathophysiology and the importance of multi-omics approaches in developing effective strategies to address the impact of loss of functional AFG3L2. Our data also highlight the value of immortalized lymphoblastoid cells as a tool for pre-clinical testing and research, offering a detailed biochemical fingerprint that enhances our understanding of SPAX5 and identifies potential areas for further investigation.PMID:40051915 | PMC:PMC11882581 | DOI:10.3389/fnmol.2025.1548255

Front Plant Sci. 2025 Feb 20;16:1568039. doi: 10.3389/fpls.2025.1568039. eCollection 2025.NO ABSTRACTPMID:40051876 | PMC:PMC11882544 | DOI:10.3389/fpls.2025.1568039

Heliyon. 2025 Feb 13;11(4):e42668. doi: 10.1016/j.heliyon.2025.e42668. eCollection 2025 Feb 28.ABSTRACTAdult neural stem cells divide to produce neurons that migrate to preexisting neuronal circuits in a process named adult neurogenesis. Adult neurogenesis is one of the most exciting areas of current neuroscience, and it may be involved in a range of brain functions, including cognition, learning, memory, and social and behavior changes. While there is a growing number of multi-omics studies on adult neurogenesis, generalized analyses from a multi-omics perspective are lacking. In this review, we summarize studies related to genomics, metabolomics, proteomics, epigenomics, transcriptomics, and microbiomics of adult neurogenesis, and then discuss their future research priorities and potential neighborhoods. This will provide theoretical guidance and new directions for future research on adult neurogenesis.PMID:40051854 | PMC:PMC11883395 | DOI:10.1016/j.heliyon.2025.e42668

Front Cell Infect Microbiol. 2025 Feb 20;14:1497563. doi: 10.3389/fcimb.2024.1497563. eCollection 2024.ABSTRACTINTRODUCTION: Xingnao Jiutan tablets (XNJT), a compound Chinese medicine, have been applied to the treatment of the sequelae of cerebral thrombosis or cerebral hemorrhage, transient cerebral ischemia, and central retinal vein obstruction, etc., but the underlying mechanisms are not yet clear. This research focused on examining the impact of XNJT for cerebral ischemia/reperfusion (MCAO/R) injury, utilizing gut microbiota and metabolomic studies.METHODS: The primary components of XNJT were identified through the application of the HPLC technique. We established a MCAO/ R model in mice and conducted behavioral evaluations, cerebral blood flow measurements, and TTC staining. We used ELISA, high-throughput 16S rDNA gene sequencing, and metabolomics techniques to detect inflammatory factors, microbial populations, and metabolites, respectively. Finally, we performed Spearman correlation analysis to investigate the relationships among gut microbiota and metabolites, comprehensively exploring the mechanisms of XNJT to alleviate cerebral ischemia-reperfusion injury.RESULTS: We discovered that XNJT effectively enhanced neurological performance, alleviated cerebral infarction, diminished neuronal cell death, and increased cerebral blood flow. Moreover, XNJT downregulated the secretion of pro-inflammatory cytokines like TNF, IL-6, and IL-1b. Additionally, XNJT improved gut microbiota levels in MCAO/R mice, particularly Bacteroides, Firmicutes, Escherichia-Shigella, and Ligilactobacillus. Furthermore, XNJT primarily modulated differential metabolites in the gut through Glycerophospholipid, Linoleic acid, and Sphingolipid metabolism pathways. Spearman correlation analysis revealed significant associations among intestinal microbiota and various metabolites.DISCUSSION: In summary, our findings suggest that XNJT can improve cerebral ischemia/reperfusion injury outcomes, reduce inflammatory responses, and regulate gut microbiota and differential metabolites. It's possible that the potential mechanisms are connected to controlling gut microbiota and metabolism.PMID:40051840 | PMC:PMC11882549 | DOI:10.3389/fcimb.2024.1497563

Hortic Res. 2024 Nov 27;12(3):uhae335. doi: 10.1093/hr/uhae335. eCollection 2025 Mar.ABSTRACTBottle gourd (Lagenaria siceraria (Molina) Standl) is a widely distributed Cucurbitaceae species, but gaps and low-quality assemblies have limited its genomic study. To address this, we assembled a nearly complete, high-quality genome of the bottle gourd (Pugua) using PacBio HiFi sequencing and Hi-C correction. The genome, being 298.67 Mb long with a ContigN50 of 28.55 Mb, was identified to possess 11 chromosomes, 11 centromeres, 18 telomeres, and 24 439 predicted protein-coding genes; notably, gap-free telomere-to-telomere assembly was accomplished for seven chromosomes. Based on the Pugua genome, the transcriptomic and metabolomic combined analyses revealed that amino acids and lipids accumulate during the expansion stage, while sugars and terpenoids increase during ripening. GA4 and genes of the Aux/IAA family mediate fruit expansion and maturation, while cell wall remodeling is regulated by factors such as XTHs, EXPs, polyphenols, and alkaloids, contributing to environmental adaptation. GGAT2 was positively correlated with glutamate, a source of umami, and SUS5 and SPS4 expression aligned with sucrose accumulation. This study provides a valuable genetic resource for bottle gourd research, enhancing the understanding of Cucurbitaceae evolution and supporting further studies on bottle gourd development, quality, and genetic improvement.PMID:40051576 | PMC:PMC11883228 | DOI:10.1093/hr/uhae335

Front Cardiovasc Med. 2025 Feb 20;12:1549900. doi: 10.3389/fcvm.2025.1549900. eCollection 2025.ABSTRACTBACKGROUND: Kawasaki disease (KD) primarily affects children as an acute systemic vasculitis. Numerous studies indicated an elevated risk of cardiovascular disease due to metabolic disturbances. Despite this knowledge, the specific metabolic modes involved in KD remain unclear.METHODS: We examined the metabolome of individuals with 108 KD and 52 non-KD controls (KD vs. nKD) by ultraperformance liquid chromatography (UPLC) and tandem mass spectrometry (MS).RESULTS: Differential analysis uncovered the disturbed production of bile acids and lipids in KD. Furthermore, we investigated the impact of treatment, intravenous immunoglobulin (IVIG) resistance, and coronary artery (CA) occurrence on the metabolome. Our findings suggested that IVIG treatment alters the lipid and amino acid metabolism of KD patients. By orthogonal projections to latent structures discriminant analysis (OPLS-DA), there was no significant difference between the coronary injury groups and non-coronary injury groups, and IVIG resistance didn't appear to cause the metabolic change in KD patients.CONCLUSIONS: Patients with KD exhibit metabolic abnormalities, particularly in bile acids and lipids. IVIG interventions may partially ameliorate these lipid abnormalities.PMID:40051431 | PMC:PMC11882569 | DOI:10.3389/fcvm.2025.1549900

JHEP Rep. 2024 Dec 16;7(3):101289. doi: 10.1016/j.jhepr.2024.101289. eCollection 2025 Mar.ABSTRACTBACKGROUND & AIMS: Exercise is a key component of lifestyle management in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but neither its therapeutic effect on the active stage of the disease, that is metabolic dysfunction-associated steatohepatitis (MASH) nor the mediating mechanisms have been characterized. Therefore, we performed multi-omic phenotyping of patients with MASLD-MASH on an exercise program.METHODS: Fifteen patients with MASLD conducted high-intensity interval training (HIIT) combined with home-based training for 12 weeks. MASLD was evaluated using histology, transient elastography, and multiparametric magnetic resonance imaging (MRI) before and after the intervention. Change in maximal oxygen consumption (VO2max) and MRI-determined liver fat were compared with a control group of patients with MASLD (n = 22). RNA sequencing was performed on liver, muscle, and fat biopsies of patients in the exercise group. Stool was analyzed by shotgun metagenomics and untargeted metabolomics was performed on plasma, urine, adipose, and stool.RESULTS: HIIT increased VO2max by 10.1% and improved mitochondrial metabolism in skeletal muscle, indicating improved cardiorespiratory fitness and adherence. VO2max increased significantly in the exercise group compared with controls. Histologically, no reduction in steatosis, MASH, or liver fibrosis was observed; however, transient elastography tended to improve. MRI-determined liver fat did not change in the exercise group compared with controls. HIIT induced changes in mRNA expression of genes related to beiging of adipose tissue and fibrogenesis in liver. In addition, specific gut microbial taxa and metabolites changed.CONCLUSIONS: HIIT increased cardiorespiratory fitness and induced beneficial gene expression changes in muscle, adipose tissue, and liver, but without translation into histological improvement of MASLD. Longer exercise intervention trials are warranted to validate or refute current recommendations for exercise as a cornerstone treatment for MASLD-MASH.IMPACT AND IMPLICATIONS: Despite exercise being considered as a key component of lifestyle management for steatotic liver disease, neither the clinical effects nor the mechanisms involved are completely understood. We show that a high-intensity interval training (HIIT) program in 15 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) improved cardiorespiratory fitness, compared with 22 control patients with MASLD who did not participate in an exercise program, however, it did not improve MASLD. HIIT induced a positive effect on fat tissue and muscle metabolism which was accompanied with changes in certain gut bacteria and metabolites in blood and urine. These findings improve our understanding of the effects of exercise on the whole-body metabolism in relation to steatotic liver disease. As such, this study provides a basis for future exercise interventions in patients with MASLD, required to thoroughly test current guideline advice for exercise as a cornerstone treatment for MASLD of all stages.CLINICAL TRIAL REGISTRY: Dutch Trial Register (registration number NL7932).PMID:40051412 | PMC:PMC11883402 | DOI:10.1016/j.jhepr.2024.101289

New Phytol. 2025 Mar 7. doi: 10.1111/nph.70022. Online ahead of print.ABSTRACTLipids play crucial roles in plant-microbe interactions, functioning as structural components, signaling molecules, and microbe-associated molecular patterns (MAMPs). However, the mechanisms underlying lipid perception and signaling in plants remain largely unknown. Here, we investigate the immune responses activated in barley (Hordeum vulgare) by lipid extracts from the beneficial root endophytic fungus Serendipita indica and compare them to responses elicited by chitohexaose and the fungal sterol ergosterol. We demonstrate that S. indica lipid extract induces hallmarks of pattern-triggered immunity (PTI) in barley. Ergosterol emerged as the primary immunogenic component and was detected in the apoplastic fluid of S. indica-colonized barley roots. Notably, S. indica colonization suppresses the ergosterol-induced burst of reactive oxygen species (ROS) in barley. By employing a multi-omics approach, which integrates transcriptomics, phosphoproteomics, and metabolomics, we provide evidence for the phosphorylation of phosphatidylinositol phosphate (PIP) metabolic enzymes and activation of diterpene biosynthesis upon exposure to fungal lipids. Furthermore, we show that phosphatidic acid (PA) enhances lipid-mediated apoplastic ROS production in barley. These findings indicate that plant lipids facilitate immune responses to fungal lipids in barley, providing new insights into lipid-based signaling mechanisms in plant-microbe interactions.PMID:40051371 | DOI:10.1111/nph.70022

Clin Cardiol. 2025 Mar;48(3):e70112. doi: 10.1002/clc.70112.ABSTRACTBACKGROUND AND OBJECTIVE: Atrial fibrillation (AF), a common arrhythmic disorder, is increasing in prevalence annually and has become an important public health problem that jeopardizes human health. Metabolites are small molecules produced in the process of metabolic reactions, and they can affect the risk of disease and possibly become targets for disease management.METHODS: We used two-sample and bidirectional MR to explore potential causal associations between lipid groups and AF. Two-step MR analysis was used to explore whether plasma metabolites mediated a causal effect from lipidomes to AF.RESULT: We assessed the effect of 179 lipids on AF using IVW models and observed that 8 lipids were associated significantly with AF (p < 0.05). Likewise, we assessed the effect of 1091 metabolites and 309 metabolite ratios on AF and observed that 22 metabolites were significantly associated with AF (p < 0.05). We analyzed the blood metabolites above as mediators in the pathway from the lipidomes above to AF. We found that levels. Of lipid sterol ester (27:1/18:3) were associated with lower homoarginine levels, and lower metabolite homoarginine levels were associated with an increased risk of AF.CONCLUSION: Our study identified a causal relationship between plasma liposomes and AF, and additionally found that the plasma metabolite homoarginine levels can act as a mediator of the lipid sterol ester in its effect on AF.PMID:40051326 | DOI:10.1002/clc.70112

J Proteome Res. 2025 Mar 7;24(3):977-978. doi: 10.1021/acs.jproteome.5c00147.NO ABSTRACTPMID:40051301 | DOI:10.1021/acs.jproteome.5c00147

J Transl Med. 2025 Mar 6;23(1):285. doi: 10.1186/s12967-025-06310-y.ABSTRACTBACKGROUND: Knee osteoarthritis is a common degenerative joint disease involving multiple pathological processes, including energy metabolism, cartilage repair, and osteogenesis. To investigate the alterations in critical metabolic pathways and differential proteins in osteoarthritis patients through metabolomic and proteomic analyses and to explore the potential mechanisms underlying synovial osteogenesis during osteoarthritis progression.METHODS: Metabolomics was used to analyze metabolites in the synovial fluid and synovium of osteoarthritis patients (osteoarthritis group: 10; control group: 10), whereas proteomics was used to examine differential protein expression. Alkaline phosphatase activity was assessed to evaluate osteogenesis.RESULTS: Upregulation of the tricarboxylic acid cycle: Significant upregulation of the tricarboxylic acid cycle in the synovial fluid and synovium of osteoarthritis patients indicated increased energy metabolism and cartilage repair activity. Arginine metabolism and collagen degradation: Elevated levels of ornithine, proline, and hydroxyproline in the synovial fluid reflect active collagen degradation and metabolism, contributing to joint cartilage breakdown. Abnormal Phenylalanine Metabolism: Increased phenylalanine and tyrosine metabolite levels in osteoarthritis patients suggest their involvement in cartilage destruction and osteoarthritis progression. Synovial osteogenesis: Increased expression of type I collagen in the synovium and elevated alkaline phosphatase activity confirmed the occurrence of osteogenesis, potentially driven by the differentiation of synovial fibroblasts, mesenchymal stem cells, and hypertrophic chondrocytes. Relationships between differential proteins and osteogenesis: FN1 and TGFBI are closely associated with synovial osteogenesis, while the upregulation of energy metabolism pathways provides the energy source for osteogenic transformation.CONCLUSIONS: Alterations in energy metabolism, cartilage repair, and osteogenic mechanisms are critical. The related metabolites and proteins have potential as diagnostic and therapeutic targets for osteoarthritis.PMID:40050855 | DOI:10.1186/s12967-025-06310-y

Genes Nutr. 2025 Mar 6;20(1):4. doi: 10.1186/s12263-025-00763-y.ABSTRACTBACKGROUND: The TCF7L2 gene is a significant genetic factor contributing to the risk of metabolic and cardiovascular diseases (CVD). We previously found that subjects with the TT genotype of TCF7L2 rs7903146 variant, who consume a low-fat diet (LF) had a higher incidence of stroke than subjects with the CC genotype. Yet this association was abolished in subjects with the TT genotype who consumed a Mediterranean-type diet (MetD). However, the mechanism by which MetD diet modulates the association between TCF7L2 and CVD risk is unclear. This study aims to validate these findings under real-world conditions and clinical practice to elucidate the biological mechanisms involved in this correlation.METHODS: Thirty-five participants with BMI ranging from 27 to 34 kg/m2 were recruited based on rs7903146 genotype. Of those consented to participate, 21 had the CC and 14 had the TT genotype. Participants were randomly assigned to two dietary intervention groups, ensuring an equal distribution of CC and TT carriers. Each participant followed one of two diets (LF or MetD) for one week, followed by a 10-day washout period before switching to the other diet for one week. Blood samples were collected before and after each diet for metabolomic analysis using nuclear magnetic resonance (NMR) spectroscopy. The differential effect of the diets on triglyceride-rich lipoproteins was determined based on TCF7L2 genotype.RESULTS: The MetD significantly reduced triglyceride-rich lipoprotein concentrations compared to the LF diet. After consuming the LF diet, TT carriers exhibited more small VLDL particles, potentially contributing to CVD risk compared to CC carriers. However, this difference in risk was not observed with the MetD. Furthermore, the order in which the two diets were crossed affected the triglyceride-rich lipoprotein profile, with LF-MetD regimen showing a stronger effect on triglyceride-rich lipoproteins (TRL) levels than the MetD-LF regimen.CONCLUSIONS: Our findings suggest that rs7903146 TT carriers benefit more from a MetD than a LF diet in terms of their triglyceride-rich lipoprotein profile, which may reduce their risk of CVD. These results support the notion that genotype is a factor in determining the extent to which the MetD affects cardiovascular health.PMID:40050721 | DOI:10.1186/s12263-025-00763-y