Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Metabolomic and Proteomic Profiling of Serum-Derived Extracellular Vesicles from Early-Stage Amyotrophic Lateral Sclerosis Patients

Sat, 15/02/2025 - 12:00
J Mol Neurosci. 2025 Feb 15;75(1):21. doi: 10.1007/s12031-025-02315-w.ABSTRACTThe identification of reliable biomarkers for amyotrophic lateral sclerosis (ALS) is an unmet medical need for the development of diagnostic and therapeutic strategies. Brain-derived extracellular vesicles (EVs) have been described in peripheral blood serum and used as a direct readout of the status of the central nervous system. Here, we aimed to explore exosome-enriched EVs (referred to simply as EVs) from ALS patients via omics analysis at an early disease stage. Serum EVs were obtained from 9 healthy controls and 9 ALS patients. After EV purification, proteomic (LC‒MS/MS followed by TimsTOF Pro Mass Spectrometry) and metabolomic (Q Exactive mass spectrometer) analyses were performed. No differences in the size or concentration of EVs were observed between the controls and ALS patients. Proteomic analysis revealed 45 proteins differentially expressed in the EVs of ALS patients compared with those of controls. Metabolomic analysis revealed several distinctly represented metabolites involved in the citrate cycle and complex lipid metabolism between patients and controls. Interomics correlation analysis revealed 2 modules that were strongly associated with ALS and included several lipid metabolism-related proteins and metabolites. This study is the first to evaluate EVs by integrated proteomics and metabolomics in early-stage ALS patients, highlighting the technological progress in global inter-omics explorations of small biological samples. The differences observed in the levels of several exosomal proteins and metabolites, including phospholipids, could be used to identify serum biomarkers and novel players involved in ALS pathogenesis.PMID:39954028 | DOI:10.1007/s12031-025-02315-w

Unanticipated differences in the rat plasma metabolome of genistein and daidzein

Sat, 15/02/2025 - 12:00
Arch Toxicol. 2025 Feb 15. doi: 10.1007/s00204-025-03967-8. Online ahead of print.ABSTRACTGenistein (GEN) and daidzein (DAI) are soy isoflavones known to bind to estrogen receptors. Overall health effects of GEN and DAI in humans exhibit a dual nature, presenting both health benefits and concerns related to their interaction with the estrogen receptor. The metabolomes of these isoflavones were determined in 28-day oral studies in male and female Wistar rats to elucidate (1) metabolites changes, (2) compare their metabolomes with other compounds and (3) identify toxicological modes of action (MoA). Dose levels for GEN were 1000 and 300 mg/kg bw by gavage and 1000 and 300 ppm (via diet). DAI gavage dose levels were 1000 and 100 mg/kg bw. Results were evaluated using the MetaMap®Tox data base. Both compounds demonstrated metabolome profiles which were associated with estrogenic profiles and compounds, predominantly in females. However, the metabolomes were compound specific with relatively few common metabolite changes. There were no relevant matches between any GEN and any DAI treatment group indicating that both compounds are substantially different from metabolome perspective. Ranking of the metabolome patters for GEN and DAI with ≥ 1000 compounds in the MetaMap®Tox database revealed correlations with estrogenic and other hormonally active compounds. GEN-treated females correlated best with Cabergoline, a dopamine D2 receptor agonist, DAI females with tamoxifen and diethylstilbestrol, suggesting that even their estrogenic activity may be different. Beyond estrogenic effects, the high dose (HD) DAI metabolome indicated altered fatty acid metabolism associated with PPAR-alpha activation. For GEN, there was an indication of ethanolamine-like liver effects. Dose levels without estrogenic effects for GEN were 1000 and 100 mg/kg bw for males and females respectively, there were no estrogenic effects in the feeding studies. For DAI males, the no estrogenic effect level was 300 mg/kg bw, for females < 100 mg/kg bw, suggesting that DAI may be a more potent estrogen than GEN in rats.PMID:39954026 | DOI:10.1007/s00204-025-03967-8

Ancestral bisphenol A exposure led to non-alcoholic fatty liver disease and sex-specific alterations in proline and bile metabolism pathways in the liver

Sat, 15/02/2025 - 12:00
Environ Toxicol Chem. 2025 Jan 6:vgae081. doi: 10.1093/etojnl/vgae081. Online ahead of print.ABSTRACTEndocrine-disrupting chemicals can induce metabolic alterations, resulting in diseases such as obesity, diabetes, and fatty liver disease, which can be inherited by offspring inhabiting uncontaminated environments. Bisphenol A (BPA), a well-known endocrine disruptor, can induce endocrine disruption, leading to metabolic disorders in subsequent generations without further exposure to BPA via nongenetic transgenerational inheritance. Using medaka as an animal model, we reported that ancestral BPA exposure leads to transgenerational nonalcoholic fatty liver disease (NAFLD) in grandchildren four generations after the initial exposure. It is unclear if transgenerational NAFLD developed because ancestral BPA exposure differs from that developed due to direct and continuous BPA exposure because the transgenerational disease develops in the absence of the stressor. We induced transgenerational NAFLD in medaka with ancestral BPA exposure (10 µg/L) at the F0 generation and examined transcriptional and metabolomic alterations in the liver of the F4 generation fish that continued to develop NAFLD. To understand the etiology of NAFLD in unexposed generations, we performed nontargeted liquid chromatography-mass spectrometry-based metabolomic analysis in combination with bulk RNA sequencing and determined biomarkers, co-expressed gene networks, and sex-specific pathways triggered in the liver. An integrated analysis of metabolomic and transcriptional alterations revealed a positive association with the severity of the NAFLD disease phenotype. Females showed increased NAFLD severity and had metabolic disruption involving proline metabolism, tryptophan metabolism, and bile metabolism pathways. The present results provide the transcriptional and metabolomic underpinning of metabolic disruption caused by ancestral BPA exposure, providing avenues for further research to understand the development and progression of transgenerational NAFLD caused by ancestral bisphenol A exposure.PMID:39953842 | DOI:10.1093/etojnl/vgae081

Aurantio-Obtusin Regulates Gut Microbiota and Serum Metabolism to Alleviate High-Fat Diet-Induced Obesity-Associated Non-Alcoholic Fatty Liver Disease in Mice

Sat, 15/02/2025 - 12:00
Phytother Res. 2025 Feb 14. doi: 10.1002/ptr.8459. Online ahead of print.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is a progressive condition with limited effective treatments. This study investigated the therapeutic effects of Aurantio-obtusin (AO), a bioactive compound from Cassiae Semen, on obesity-associated NAFLD. An obesity-related NAFLD model was established in ApoE-/- mice fed a high-fat diet (HFD) for 24 weeks, with AO administered during the last 16 weeks. Mouse body weight, adipose tissue weights, liver weights, serum lipid levels, hepatic steatosis, inflammatory damage, and colonic tissue barrier integrity were evaluated. Gut microbial communities and serum metabolic profiles were analyzed using 16S rRNA sequencing and untargeted metabolomics. Hepatic lipid metabolism-related gene expression was assessed using molecular biology techniques. AO treatment significantly ameliorated HFD-induced adiposity, hyperlipidemia, and NAFLD symptoms. It preserved intestinal barrier integrity, modulated gut microbial composition by enriching beneficial taxa, and improved serum metabolic profiles. AO favorably adjusted hepatic lipid metabolism by upregulating PPARα and CPT1A while downregulating SREBP1, FASN, and SCD1. Correlation analysis revealed significant associations among gut microbial composition, serum metabolites, and disease indicators. AO's therapeutic benefits in NAFLD might be attributed to its ability to modulate gut microbial community composition and serum metabolic profile, enhance intestinal barrier function, and regulate hepatic lipid metabolism gene expression. AO presents a promising therapeutic agent for obesity-associated NAFLD, warranting further investigation into its potential clinical applications.PMID:39953693 | DOI:10.1002/ptr.8459

ROASMI: accelerating small molecule identification by repurposing retention data

Fri, 14/02/2025 - 12:00
J Cheminform. 2025 Feb 14;17(1):20. doi: 10.1186/s13321-025-00968-8.ABSTRACTThe limited replicability of retention data hinders its application in untargeted metabolomics for small molecule identification. While retention order models hold promise in addressing this issue, their predictive reliability is limited by uncertain generalizability. Here, we present the ROASMI model, which enables reliable prediction of retention order within a well-defined application domain by coupling data-driven molecular representation and mechanistic insights. The generalizability of ROASMI is proven by 71 independent reversed-phase liquid chromatography (RPLC) datasets. The application of ROASMI to four real-world datasets demonstrates its advantages in distinguishing coexisting isomers with similar fragmentation patterns and in annotating detection peaks without informative spectra. ROASMI is flexible enough to be retrained with user-defined reference sets and is compatible with other MS/MS scorers, making further improvements in small-molecule identification.PMID:39953609 | DOI:10.1186/s13321-025-00968-8

Integrative multi-omics analysis of radionuclide-induced intestinal injury reveals the radioprotective role of L-citrulline through histone H3-mediated Cxcl3

Fri, 14/02/2025 - 12:00
J Transl Med. 2025 Feb 14;23(1):180. doi: 10.1186/s12967-025-06197-9.ABSTRACTBACKGROUND: The widespread application of nuclear technology has markedly heightened the risk of extensive, uncontrolled exposure to radiation. Nevertheless, in contrast to external irradiation, the biological impacts and countermeasures against internal irradiation from radionuclides remain inadequately characterized.METHODS: Mice were administered yttrium-90 (Y90) carbon microspheres via gavage at different dosages (0-5.0 mCi) to establish a radionuclides exposure model. A multi-omics analysis was employed to access alterations in gut microbiota, fecal and colonic metabolites profiles, and intestinal mRNA expression post-irradiation. The function of significant metabolite was validated at both cellular levels and organismal levels. Additionally, ChIP-Seq and RNA-Seq techniques were utilized to investigate the molecular mechanism underlying the actions of key metabolite.RESULTS: Exposure to Y90 resulted in intestinal damage and hematological impairment. Multi-omics analysis revealed significant alternations of gut microbiota, fecal metabolites, colonic metabolites, and intestinal mRNA expression following internal radiation exposure. Notably, L-citrulline was identified as a metabolite with changes observed in both fecal and colonic tissues, demonstrating radioprotective properties in vitro and in vivo. Mechanistically, L-citrulline facilitated the citrullination of histone H3 at the 17th site (H3Cit17), and multiple mRNAs including C-X-C motif chemokine ligand 3 (Cxcl3), were transcriptionally regulated by H3Cit17 post L-citrulline treatment. Furthermore, Cxcl3 conferred protective effects for intestinal epithelial cells against ionizing radiation.CONCLUSIONS: The research offers critical perspectives on the intestinal and gut microbiota's reaction to radionuclides exposure. It underscores the promise of L-citrulline as a radioprotective compound, which may have substantial ramifications for the formulation of strategies to mitigate radiation exposure.PMID:39953550 | DOI:10.1186/s12967-025-06197-9

Analysis of lipidomics profile of Brassica napus hybrid 'Fangyou 777' and its parents during ripening stages based on UPLC-MS/MS

Fri, 14/02/2025 - 12:00
BMC Plant Biol. 2025 Feb 14;25(1):197. doi: 10.1186/s12870-025-06220-7.ABSTRACTBACKGROUND: Lipids in rapeseed is of great significance to human health, and 'Fangyou 777' (No. GPD-2019-510073) has been identified as an excellent cultivar with high oil content. However, the change of lipid profile at different ripening stages remain unclear. Herein, UPLC-MS/MS was utilized for comprehensive lipidomics analysis of 'Fangyou 777' and its parents at four ripening stages.RESULTS: 778 lipids components across 25 subclasses were identified, and triglycerides (TGs), diglycerides (DGs), phosphatidylserines (PSs), phosphatidylinositols (PIs), phosphatidylglycerols (PGs), phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), and free fatty acids (FFAs) were identified as the dominant lipid subclass. Due to heterotic vigor, the total lipids, TGs, FFAs, lysophosphatidylglycerol (LPGs) and PSs contents in 'Fangyou 777' were significantly higher than its parents. The PCA and OPLS-DA results elucidated that lipids in 'Fangyou 777' differed obviously from its parents at S1 (17 April, 2023; 28 days before ripening, 28 DBR), S2 (1 May, 2023; 14 DBR), and S3 (15 May, 2023; ripening day). TG(18:1_18:3_22:1), TG(18:1_22:1_18:2), TG(16:0_18:1_20:1), TG(16:0_18:1_22:1), TG(20:1_18:2_20:2), TG(18:1_18:1_20:1), and FFA(24:4) were recognized as key differential lipids. The glycerolipid metabolism and unsaturated fatty acid biosynthesis were the differential metabolic pathways at S1 and S3, while glycosylphosphatidylinositol (GPI)-anchor biosynthesis and glycerophospholipid metabolism were the differential metabolic pathways at S2 and S4 (7 days after ripening/physiologically ripened for one week).CONCLUSION: This study provided a comprehensive profile to facilitate the understanding lipids accumulation in 'Fangyou 777' and its parents during ripening stages, and offered a foundation to comprehend lipid metabolism.PMID:39953462 | DOI:10.1186/s12870-025-06220-7

Genome-wide identification of starch metabolism gene families in Potentilla anserina and the expression pattern in response to abiotic stress factors

Fri, 14/02/2025 - 12:00
BMC Plant Biol. 2025 Feb 14;25(1):201. doi: 10.1186/s12870-025-06229-y.ABSTRACTBACKGROUND: The tuberous roots of Potentilla anserina (Pan), which are called silverweed cinquefoil roots, serve as a source of starch for the inhabitants of the Qinghai-Tibet Plateau. They are also regarded as a valuable tonic food and herbal medicine in the ethnic medicine system. Starch plays a crucial part in the plant's life cycle, particularly during the growth stage and in response to abiotic stress. Moreover, numerous biological processes and regulatory networks are involved in the synthesis and accumulation of starch.RESULTS: In this research, a combination of transcriptome and metabolomics approaches were employed to analyze the genes related to starch synthesis and degradation in Pan. The crucial genes involved in starch metabolism were identified, and the response characteristics of these genes to drought and low temperature treatments were investigated. Seven AMYs (Alpha-amylases) and 18 BAMs (Beta-amylases) were identified from the genome of Pan. Molecular phylogenetic analyses of AMYs and BAMs derived from 11 species of rosids were conducted respectively. AMYs of Pan and other species were clustered into 3 groups, whereas BAMs were classified into 4 groups. In the tuberous roots, when compared with the control conditions, 2 AMYs and 4 BAMs were upregulated, while 3 BAMs were downregulated, meanwhile, the contents of maltose and glucose-6-phosphate (G6P) were decreased, while the content of glucose-1-phosphate (G1P) was increased under drought treatment. In the tuberous roots under low temperature treatment, 1 BAM was upregulated, while 2 AMYs and 4 BAMs were downregulated compared with control. The response characteristics of AMYs and BAMs to drought and low temperature treatments were further verified through qPCR analysis.CONCLUSIONS: In this research, the genes associated with starch synthesis in Pan were characterized, and the functions of AMYs and BAMs in abiotic stress treatments were elucidated. An overview of evolution of AMY and BAM gene families within rosids was also provided.PMID:39953429 | DOI:10.1186/s12870-025-06229-y

Dysregulation of amino acid and lipid metabolism in patients with spondyloarthritis

Fri, 14/02/2025 - 12:00
J Int Med Res. 2025 Feb;53(2):3000605251313949. doi: 10.1177/03000605251313949.ABSTRACTOBJECTIVE: To conduct a metabolomics analysis in patients with spondyloarthritis (SpA) and compare results with those from healthy controls. The overall goal was to identify small-molecule substances that may have potential pathogenic and diagnostic significance in SpA.METHODS: This was an observational, cross-sectional, single-centre study that included patients with axial (ankylosing spondylitis [AS]), peripheral (psoriatic arthritis [PsA]) and healthy controls.RESULTS: The study included 50 patients with AS, 50 patients with PsA, and 164 controls. When compared with healthy controls, patients with SpA showed significant differences in 35 metabolites, primarily associated with amino acid and lipid metabolism. However, only two differences were found between the AS and PsA cohorts (glucose and glycerol).CONCLUSIONS: Our data suggest that patients with SpA exhibit significant disruptions in amino acid and lipid metabolism. The large number of identified metabolites offers promising opportunities, both for discovering new SpA biomarkers and for gaining a deeper understanding of the pathophysiology of these chronic inflammatory diseases.PMID:39953426 | DOI:10.1177/03000605251313949

Regulation of antibiotic persistence and pathogenesis in Acinetobacter baumannii by glutamate and histidine metabolic pathways

Fri, 14/02/2025 - 12:00
BMC Microbiol. 2025 Feb 14;25(1):74. doi: 10.1186/s12866-024-03654-1.ABSTRACTBACKGROUND: Metabolite production is essential for the proliferation and environmental adaptation of all living organisms. In pathogenic bacteria, metabolite exchange during host infection can regulate their physiology and virulence. However, there is still much unknown about which specific metabolic pathways in pathogenic bacteria respond to changes in the environment during infections. This study examines how pathogenic bacterium Acinetobacter baumannii uses particular metabolic pathways to regulate its ability to antibiotic persistence and pathogenesis.RESULTS: To determine specific metabolic pathways in pathogenic antibiotic resistance bacteria, metabolite profiles of bacteria were constructed using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry and multivariate statistical analysis. A. baumannii generates amino acid derivative metabolites, which are precursors for fatty acid production. Comparative genomic analysis identified specific genes regulating the production of these metabolites and fatty acids in A. baumannii. Inactivation of genes involved in glutamate metabolism, gdhA, aspB, murI1, and racD, impairs antibiotic persistence, while inactivation of the hisC gene, encoding histidinol - phosphate aminotransferase enzyme in histidine metabolic pathway, increases bacterial survival inside macrophages during infections.CONCLUSIONS: This study reports that A. baumannii regulates antibiotic persistence and pathogenesis through glutamate and histidine metabolic pathways, respectively. These findings suggest that specific metabolic pathways regulate bacterial pathogenesis and antibiotic persistence during infections, providing potential therapeutic targets for pathogenic bacteria.PMID:39953398 | DOI:10.1186/s12866-024-03654-1

High-ammonia microenvironment promotes stemness and metastatic potential in hepatocellular carcinoma through metabolic reprogramming

Fri, 14/02/2025 - 12:00
Discov Oncol. 2025 Feb 14;16(1):182. doi: 10.1007/s12672-025-01922-8.ABSTRACTBACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent and aggressive form of liver cancer, characterized by frequent recurrence and metastasis, which remain significant obstacles to effective treatment. Ammonia accumulates in the tumor microenvironment of HCC due to dysfunction in the urea cycle, but the detailed impact of ammonia on HCC cells remains insufficiently understood.METHODS: We exposed HCC cell lines to high concentrations of ammonium chloride to evaluate alterations in proliferation, stemness, and migratory potential. After ammonia removal, changes in cellular behavior were assessed using colony formation, and spheroid assays. Transcriptomic and metabolomic analyses were conducted to investigate ammonia-induced metabolic reprogramming and alterations in gene expression. Additionally, animal models were employed to validate the impact of ammonia on tumor growth and metastasis.RESULTS: Exposure to high-ammonia conditions transiently suppressed HCC cell proliferation without inducing apoptosis. However, following ammonia removal, cells demonstrated increased proliferation, enhanced spheroid formation, and elevated migratory capacity. Transcriptomic analysis revealed the upregulation of genes associated with cell adhesion, migration, and glycolysis. Concurrently, metabolomic profiling indicated increased lactate production, facilitating the aggressive behavior of HCC cells after ammonia withdrawal. Animal experiments confirmed that high-ammonia exposure accelerated tumor growth and metastasis.CONCLUSION: Ammonia exerts a dual effect on HCC progression: it initially suppresses cell growth but later promotes stemness, proliferation, and metastasis through metabolic reprogramming. Targeting ammonia metabolism or glycolysis in the tumor microenvironment may represent a promising therapeutic strategy for mitigating HCC recurrence and metastasis. Future studies utilizing clinical samples are required to validate these findings and identify potential therapeutic strategies targeting ammonia metabolism.PMID:39953190 | DOI:10.1007/s12672-025-01922-8

An international perspective on the future of systemic sclerosis research

Fri, 14/02/2025 - 12:00
Nat Rev Rheumatol. 2025 Feb 14. doi: 10.1038/s41584-024-01217-2. Online ahead of print.ABSTRACTSystemic sclerosis (SSc) remains a challenging and enigmatic systemic autoimmune disease, owing to its complex pathogenesis, clinical and molecular heterogeneity, and the lack of effective disease-modifying treatments. Despite a century of research in SSc, the interconnections among microvascular dysfunction, autoimmune phenomena and tissue fibrosis in SSc remain unclear. The absence of validated biomarkers and reliable animal models complicates diagnosis and treatment, contributing to high morbidity and mortality. Advances in the past 5 years, such as single-cell RNA sequencing, next-generation sequencing, spatial biology, transcriptomics, genomics, proteomics, metabolomics, microbiome profiling and artificial intelligence, offer new avenues for identifying the early pathogenetic events that, once treated, could change the clinical history of SSc. Collaborative global efforts to integrate these approaches are crucial to developing a comprehensive, mechanistic understanding and enabling personalized therapies. Challenges include disease classification, clinical heterogeneity and the establishment of robust biomarkers for disease activity and progression. Innovative clinical trial designs and patient-centred approaches are essential for developing effective treatments. Emerging therapies, including cell-based and fibroblast-targeting treatments, show promise. Global cooperation, standardized protocols and interdisciplinary research are vital for advancing SSc research and improving patient outcomes. The integration of advanced research techniques holds the potential for important breakthroughs in the diagnosis, treatment and care of individuals with SSc.PMID:39953141 | DOI:10.1038/s41584-024-01217-2

Hosta plantaginea flower ameliorates chronic pharyngitis by suppressing inflammation via the JAK-STAT/PI3K/MAPK signaling axis in rats

Fri, 14/02/2025 - 12:00
Chem Biodivers. 2025 Feb 14:e202403254. doi: 10.1002/cbdv.202403254. Online ahead of print.ABSTRACTHosta plantaginea flower is an important Chinese herb in treating chronic pharyngitis (CP); however, its pharmacodynamics against CP and the underlying mechanisms remain unclear. This study demonstrated that the ethyl acetate (HPB) and n-butanol (HPC) fractions of the H. plantaginea flower were identified as the active fractions against CP, significantly increasing the body weight, improving damaged pharyngeal tissues, and reducing TNF-α, PGE2, IL-1β, and IL-6 levels in rats induced by 5% ammonia solution. Metabolomics studies identified 55 differential metabolites, with 26 being reversely regulated by HPB and HPC. These 26 metabolites are closely associated with phosphoinositide 3-kinase-protein kinase B (PI3K-Akt), just another kinase-signal transducers and activators of transcription (JAK-STAT), mitogen-activated protein kinases (MAPKs), and nuclear factor kappa-B (NF-κB) pathways. Mechanically, HPB and HPC prominently suppressed the expression of phosphorylated PI3K, Akt1, JAK1, STAT3, JNK, p38, Erk, p65, and inhibitor of NF-κB (IκBα) proteins. Finally, HPLC analysis identified flavonoids as the primary phytochemicals of HPB and HPC. In conclusion, HPB and HPC are the main active fractions of H. plantaginea flower against CP, acting through regulating energy metabolism and inhibiting PI3K-Akt, JAK-STAT, MAPKs, and NF-κB signaling pathways, and the flavonoids are the primary constituents.PMID:39952902 | DOI:10.1002/cbdv.202403254

Study on the Chemical Constituents of Different Parts of Xanthoceras Sorbifolia Bunge Based on Plant Metabolomics

Fri, 14/02/2025 - 12:00
Chem Biodivers. 2025 Feb 14:e202500072. doi: 10.1002/cbdv.202500072. Online ahead of print.ABSTRACTX. sorbifolia is valued in food, landscape, and medicine, with its husk containing triterpenoid Triterpenoids known for anti-Alzheimer's effects. This study, using UHPLC-HRMS and plant metabolomics, compared the chemical profiles of different parts of X. sorbifolia to assess their potential for replacing the husk in medicinal use. The findings show that only the bark and wood contain small amounts of triterpene Triterpenoids, which cannot substitute the husk's medicinal value. These results support the quality control and clinical application of the husk.PMID:39952894 | DOI:10.1002/cbdv.202500072

LC-MS/MS-based metabolomics and multivariate statistical analysis reveal the mechanism of yeast extracellular proteases on myofibrillar protein degradation, metabolite development and sensory characteristics improvement

Fri, 14/02/2025 - 12:00
Food Microbiol. 2025 Jun;128:104715. doi: 10.1016/j.fm.2024.104715. Epub 2024 Dec 17.ABSTRACTYeast extracellular proteases play a key role in developing the taste of dry-cured ham, whereas the mechanism of yeast proteases on taste formation of dry-cured ham is not fully studied. The proteases characteristics of yeast isolated form Jinhua ham, hydrolysis capacities for myofibrillar proteins (MP), free amino acid contents, metabolite compositions, taste parameters and the relationship between metabolites and taste parameters were investigated to reveal the mechanism of Rhodotorula mucilaginosa AUMC 9298 (RM) and Candida parapsilosis d70a (CP) proteases on MP hydrolysis and taste development of dry-cured ham. The proteases of RM and CP showed high hydrolysis activities at the conditions of pH 5.0-8.0 and 30-50 °C. The proteases of RM showed higher capability to degrade myosin compared with CP proteases and Pichia kudriavzevii XS-5 (PK) proteases. The total free amino acid contents increased from 18.44 mg/100 mL in PK to 33.91 mg/100 mL in RM and 25.28 mg/100 mL in CP after 4 h hydrolysis of MP. Thirty-two metabolites were identified by LC-MS/MS, and peptides and amino acid derivatives were the key components of MP hydrolysates. The scores of umami, richness and aftertaste showed the largest values in RM among these groups. PLS-DA and correlation demonstrated that aspartic acid, N-Methyl-aspartic acid, Glu-Glu, γ-Glu-Cys, glutamic acid, γ-Glu-Glu and γ-Glu-Gln were positive correlation with the improvement of umami, richness and aftertaste.PMID:39952759 | DOI:10.1016/j.fm.2024.104715

Enhancing the quality of dark tea through fermentation with Aspergillus niger: Unveiling aroma and taste characteristics

Fri, 14/02/2025 - 12:00
Food Microbiol. 2025 Jun;128:104721. doi: 10.1016/j.fm.2025.104721. Epub 2025 Jan 3.ABSTRACTAmidst the increasing demand for premium dark tea, the utilization of Aspergillus niger-inoculated fermentation has emerged as a potential solution to address the challenges associated with extended processing cycles and inconsistent quality. This study comprehensively investigated the efficacy and mechanisms of A. niger PW-2 inoculation in enhancing dark tea quality compared to spontaneous fermentation, using metabolomics, electronic tongue, molecular docking, and high-throughput sequencing. A. niger PW-2 shaped the fungal community within 7 days, degrading terpene glycosides and lactones while generating terpenoids and unsaturated fatty acids, which enriched the floral aroma of PW-2-inoculated fermentation dark tea (AF). Flavonoid degradation and reduced theaflavins/thearubigins levels in AF decreased astringency, while increased bitter dipeptides and isoflavonoids enhanced bitterness, and the accumulation of umami dipeptides and theabrownins improved umami taste perception of AF. Molecular docking identified key compounds responsible for astringency (kaempferol glycosides), bitterness (6″-caffeoylisoorientin, kaempferol 4'-glucoside 7-rhamnoside, dihydrodaidzein 7-O-glucuronide), and umami (3-O-p-trans-coumaroylalphitolic acid, dihydrodaidzein 7-O-glucuronide, 1-methoxyphaseollidin). Overall, A. niger PW-2 inoculation accelerates fermentation process and enhances flavor characteristics of dark tea, offering a promising approach for high-quality dark tea production.PMID:39952746 | DOI:10.1016/j.fm.2025.104721

Endophytic fungus Umbelopsis sp. TM01 as high-activity alternative to Tricholoma matsutake

Fri, 14/02/2025 - 12:00
Bioresour Technol. 2025 Feb 12:132216. doi: 10.1016/j.biortech.2025.132216. Online ahead of print.ABSTRACTTricholoma matsutake, a rare fungus, is highly valued for its remarkable nutritional content, making it a sought-after biomass resource in both the cosmetics and food sectors. However, its scarcity and restricted natural growth impede large-scale utilization. An endophytic fungus, Umbelopsis sp. TM01, was successfully isolated from the fruiting body of T. matsutake. Research on the biological activity and cytotoxicity of the extract from Umbelopsis sp. TM01 (UFE) and the extract from T. matsutake (TME) showed that UFE outperformed TME in biological activity and had lower cytotoxicity. In the cosmetics-relevant bio-functions, UFE exhibited more potent anti-tyrosinase activity, greater anti-wrinkle efficacy and comparable wound-healing effect to that of TME. UFE was safe for human dermal fibroblasts even at 10% concentration. Metabolomic analysis revealed UFE had diverse secondary metabolites. All in all, Umbelopsis sp. TM01 has great potential as a substitute for T. matsutake in the cosmetics industry.PMID:39952620 | DOI:10.1016/j.biortech.2025.132216

Joint transcriptomics and metabolomics unveil the protective mechanism of tamarind seed polysaccharide against antibiotic-induced intestinal barrier damage

Fri, 14/02/2025 - 12:00
Int J Biol Macromol. 2025 Feb 12:140999. doi: 10.1016/j.ijbiomac.2025.140999. Online ahead of print.ABSTRACTIntestinal barrier damage is frequently caused by antibiotic therapy, potentially leading to bacterial translocation and toxin leakage, which triggers inflammation and increases the risk of various diseases. In this study, Tamarind seed polysaccharides (TSP) with different molecular weights were administered to mice during the recovery phase from clindamycin-induced intestinal barrier damage. The results indicated that TSP restored the shortened colon length, reduced the enlarged cecum index, and decreased the elevated level of inflammatory infiltration. Biochemical testing revealed that TSP decreased the levels of intestinal permeability biomarkers and inflammatory factors that were elevated by clindamycin treatment. Transcriptomics and non-targeted metabolomics analyses respectively uncovered changes in colon gene expression and fecal metabolites. The joint analysis of these omics data identified critical pathways, including arachidonic acid metabolism, retinol metabolism, and steroid hormone biosynthesis. These findings suggest that TSP could be a promising dietary supplement for protecting the intestinal barrier and alleviating inflammation.PMID:39952497 | DOI:10.1016/j.ijbiomac.2025.140999

HADHA promotes apoptosis and inflammatory response in bovine endometrial epithelial cells by regulating transcription and metabolism

Fri, 14/02/2025 - 12:00
Int J Biol Macromol. 2025 Feb 12:140980. doi: 10.1016/j.ijbiomac.2025.140980. Online ahead of print.ABSTRACTEndometritis in dairy cows significantly impacts their reproductive performance. However, its underlying mechanisms remain unclear. Hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit-alpha (HADHA) is known to regulate the occurrence of various diseases, but its role in bovine endometritis is poorly understood. In the present study, an in vitro bovine endometrial epithelial cell (BEEC) inflammation model was constructed to explore the effects of HADHA on inflammation, proliferation, and apoptosis. Functional analyses based on HADHA interference and overexpression revealed that it positively regulated the expression of IL-6, IL-8, and IL-1β in lipopolysaccharide (LPS)-induced BEECs, enhancing reactive oxygen species (ROS) production and promoting inflammation. Concurrently, HADHA decreased the expression of PCNA, CDK2, and CDK4, inhibited mitotic transition of BEECs from S to G2 phase, and negatively regulated BEEC proliferation. It also increased BAX and Caspase-3 expression while decreasing BCL2 expression, hence promoting BEEC apoptosis. Transcriptomic and metabolomic analyses indicated that HADHA modulated inflammation in BEECs by affecting pathways such as the TGF-beta signaling pathway, fatty acid metabolism, and p53 signaling. These findings provide novel insights into HADHA's role in bovine endometritis and reveal future research directions on its regulatory mechanisms.PMID:39952496 | DOI:10.1016/j.ijbiomac.2025.140980

Integrative Omics Approaches in Cardiovascular Disease Research: Current Trends and Future Directions

Fri, 14/02/2025 - 12:00
Can J Cardiol. 2025 Feb 12:S0828-282X(25)00126-6. doi: 10.1016/j.cjca.2025.02.016. Online ahead of print.ABSTRACTCardiovascular disease (CVD) remains the leading cause of death worldwide, necessitating a deeper understanding of its complex pathophysiology. Omics technologies-genomics, transcriptomics, proteomics, and metabolomics-have revolutionized cardiovascular research, enabling high-throughput analysis of biological systems at multiple molecular levels. These tools are advancing precision medicine by uncovering molecular mechanisms underlying CVD. Traditionally, research followed a top-down approach, analyzing broad cardiovascular subsystems. However, modern high-throughput technologies support a bottom-up approach, examining molecular components first and integrating findings into larger systems. This paradigm shift, powered by big data, is transforming cardiovascular research and paving the way for more precise, personalized treatments.PMID:39952467 | DOI:10.1016/j.cjca.2025.02.016

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