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

PubMed

Improving Mitochondrial health by Pyrroloquinoline Quinone (PQQ) Prevents Ultrafine Carbon Particle (UFCP) induced Emphysema and associated Pulmonary Hypertension

Mon, 09/02/2026 - 12:00
Free Radic Biol Med. 2026 Feb 7:S0891-5849(26)00112-7. doi: 10.1016/j.freeradbiomed.2026.02.015. Online ahead of print.ABSTRACTAir pollution-induced emphysema is accompanied by changes in pulmonary vasculature, leading to pulmonary hypertension (PH) and ultimately heart failure. Pyrroloquinoline Quinone (PQQ), a potent antioxidant with cardio-protective properties, upregulates mitochondrial biogenesis and functions. Previously, we have shown that PQQ protects against PH; however, the effect of PQQ on emphysema and the mitochondrial dysfunction due to air pollution still remains unexplored. In our study, we unraveled the effect of PQQ on Ultrafine carbon particle (UFCP) induced emphysema and PH. In the in vitro studies, human lung adenocarcinoma epithelial cells (A549 cells) were exposed to UFCP (50 μg/ml) and PQQ (100 μM) for 24 hr, and following this, the redox state and mitochondrial health of the cells were examined. For the in vivo study, SD rats were administered UFCP (100 μg/dose, three times a week, intranasally) and PQQ (2 mg/kg, oral/day) for four weeks. Plethysmography, 2-D Echo, and invasive blood pressure measurement were used to study pulmonary, hemodynamic, and cardiac functions, and metabolic changes were studied by untargeted metabolomics of the lungs. PQQ treatment improved mitochondrial structure, dynamics, and biogenesis and reduced oxidative stress in UFCP-exposed A549 cells. PQQ significantly improved pulmonary functions, inflammation, structure, and muscularization of vessels in UFCP-exposed rats (#p<0.01). Metabolomics study showed improved metabolism in the lungs of PQQ-treated rats. Further, PQQ significantly reduced right ventricular pressure (RVP) and hypertrophy (RVH) in UFCP-exposed rats (#p<0.05). Our findings suggest that improving mitochondrial functions by PQQ preserves alveolar integrity and prevents pulmonary hypertension, and it can be a promising prophylactic, especially for pollution-ridden settings.PMID:41662917 | DOI:10.1016/j.freeradbiomed.2026.02.015

Linking chemical profiles to sensory quality: Insights into color and taste formation in purple leaf tea infusions

Mon, 09/02/2026 - 12:00
Food Chem. 2026 Feb 3;507:148283. doi: 10.1016/j.foodchem.2026.148283. Online ahead of print.ABSTRACTPurple leaf tea (PLT) infusions typically exhibit a distinctive purplish-red hue and bitter taste, yet their chemical-sensory links remain underexplored. We profiled 177 metabolites from sixteen green to deep purple tea accessions, with partial least squares discriminant analysis and random forest subsequently highlighting 27 differential metabolites. Multivariate analysis highlighted acylated anthocyanins, specifically delphinidin and cyanidin derivatives, as key markers linked to redness and bitterness. Photodiode array detection confirmed these pigments as primary chromophores. Crucially, addition experiments validated that specific anthocyanin ratios govern color shifts, while their accumulation significantly intensifies bitterness and astringency. Molecular docking further supported this sensory impact, revealing that acylation enhances anthocyanin binding to human bitter receptor TAS2R14 through hydrogen bonding and π-π stacking interactions. These findings link flavonoid pathway reprogramming to the chromatic and sensory divergence of PLT, offering molecular targets for breeding high-pigment, palatable tea cultivars.PMID:41662801 | DOI:10.1016/j.foodchem.2026.148283

Bacteria and Fungi Synergistically Reprogram Flavonoid Metabolites in the Pericarp of Citrus Reticulata 'Chachi' During Storage

Mon, 09/02/2026 - 12:00
Adv Sci (Weinh). 2026 Feb 9:e00267. doi: 10.1002/advs.202500267. Online ahead of print.ABSTRACTThe mature pericarp of Citrus reticulata ' Chachi ' (PCRC) is a traditional Chinese medicine known for its enhanced efficacy through long-term storage and processing. However, the specific mechanisms underlying these enhancements remain unclear. This study employed widely targeted metabolomics, microbial amplicon sequencing, and fermentation assays to investigate the microbiome 's influence on PCRC 's flavonoid profile over 0-19 years of storage. Correlation analysis revealed that the accumulation of polymethoxyflavones (PMFs) was closely linked to specific bacterial and fungal communities. Solid-state fermentation showed that Bacillus subtilis N18-1 enhanced the content of certain PMFs, while Aspergillus tubingensis P21-1 reduced them. Liquid-state assays confirmed that A. tubingensis P21-1 converted nobiletin to 3 ' -demethylnobiletin, and B. subtilis N18-1 further converted this to tangeretin. Combined with genome sequencing and molecular docking, four candidate genes were identified. The catalytic activity verification assays demonstrated that At21-68 and At21-21 catalyze the conversion of nobiletin to 3 '-demethylnobiletin, while Bs18-51 and Bs18-84 catalyze the conversion of 3 ' -demethylnobiletin to tangeretin. These findings highlight the synergistic molecular mechanism by which microorganisms modulate PMFs during PCRC aging, providing insights for optimizing medicinal plant aging through microbial biotransformation.PMID:41662488 | DOI:10.1002/advs.202500267

Integrated metabolomics and bioactivity analysis of new chrysanthemum cultivar petals: Insights into eye-protecting agents

Mon, 09/02/2026 - 12:00
PLoS One. 2026 Feb 9;21(2):e0340052. doi: 10.1371/journal.pone.0340052. eCollection 2026.ABSTRACTChrysanthemum is a globally significant economical crop. Through broadly targeted metabolomics, 58 polyphenols and 65 xanthophylls were quantitatively and qualitatively assessed in chrysanthemum petals. Carotenoids including β-cryptoxanthin, lutein stearate, lutein distearate, lutein dioleate, and lutein oleate, emerged as the primary compounds in both ligulate and tubular flowers, and their levels remaining relatively high and stable during the second to fifth stages of chrysanthemum flower development. However, the compound content varied across developmental stages and tissues. Additionally, the activity of a novel chrysanthemum cultivar extract was evaluated; at a concentration of 62.5 μg/mL, it exhibited significantly greater anti-apoptotic effects than glutathione (p < 0.001). Moreover, various concentrations of the chrysanthemum extract demonstrated a clear trend in preventing retinopathy. This study integrated chemical composition analysis with activity evaluation to offer fresh insights into the mechanism underlying the development of eye-protecting agents derived from chrysanthemum flowers.PMID:41662364 | DOI:10.1371/journal.pone.0340052

Enzyme-Catalyzed Sulfo-Tagging Accelerates 3-OH Steroid-Targeted Submetabolome Profiling

Mon, 09/02/2026 - 12:00
Anal Chem. 2026 Feb 9. doi: 10.1021/acs.analchem.5c08055. Online ahead of print.ABSTRACTAlthough derivatization is widely favored for metabolomics, the applications are dramatically narrowed by insufficient selectivity, because a given metabolite may be transferred to several products or conjugated with two or even more derivative moieties. Enzymatic derivatization may address this critical issue by attributing to superior selectivity. Human sulfotransferase 2A1 (hSULT 2A1) was utilized here to tag sulfo to 3-OH of steroids that structurally involve most cholesterol metabolites and, importantly, serve as key biomarkers for diverse diseases. Through evaluating sulfation performances by assaying 53 authentic steroids, we found: 1) great selectivity and transformation rate (>80%) existed for 3-OH sulfation; 2) sulfates exhibited diagnostic fragment ions (i.e., SO3-• and SO4-), SO3 neutral loss, and [34S - M - H]- signals; 3) optimal collision energy for either SO3-• or SO4- was linearly correlated with [M - H]- mass; and 4) better sensitivity appeared for sulfates. Molecular docking consolidated selective 3-OH sulfation. hSULT 2A1-catalyzed sulfo-tagging was applied for 3-OH steroid-targeted submetabolome profiling of Bufonis Venenum (BV), a promising anticancer agent. Sixty steroid 3-sulfates were captured and quantitatively compared, and significant variations existed within 20 batches of BV. Together, hSULT 2A1-mediated sulfation is meaningful for submetabolomics targeting on 3-OH steroids, leading to new insights toward enzyme-catalyzed derivative metabolomics.PMID:41661686 | DOI:10.1021/acs.analchem.5c08055

Hic-5 promotes the progression of nonalcoholic steatohepatitis by regulating hepatocellular fatty acid metabolism through the PTEN/PGE2/EP4 axis

Mon, 09/02/2026 - 12:00
Mol Biomed. 2026 Feb 9;7(1):10. doi: 10.1186/s43556-026-00409-4.ABSTRACTNonalcoholic steatohepatitis (NASH) is a metabolic disease characterized by hepatic steatosis and inflammation among other features. Dysregulated lipid metabolism is crucial in the pathogenesis of NASH. However, its regulatory mechanisms remain intricate and poorly elucidated. Hepatic stellate cells (HSCs) have been reported to contribute to hepatocellular lipid metabolism dysregulation and aggravate NASH progression. However, the potential mechanisms remain unclear. Here, we demonstrate that hydrogen peroxide-inducible clone 5 (Hic-5), which is highly expressed in HSCs within the liver, is elevated in NASH patients and mouse models. Hic-5 deficiency alleviates hepatic steatosis, and liver metabolomics revealed reduced fatty acid levels. Meanwhile, RNA-sequencing revealed that Hic-5 deficiency increases AMPK phosphorylation. Additionally, HSC-specific overexpression of Hic-5 exacerbates NASH severity. Co-culture experiments indicated that Hic-5 increases hepatocellular fatty acid synthesis. Cellular transcriptomic analysis and validation revealed that prostaglandin E2 (PGE2), secreted by HSCs, mediates hepatocellular fatty acid synthesis. Mechanistically, the N-terminal domain of Hic-5 binds c-Src, leading to phosphorylation of PTEN, which is bound to the C-terminal domain. This event subsequently induces phosphorylation and nuclear translocation of the transcription factor SP1, ultimately increasing PGE2 secretion. Finally, Hic-5 promotes hepatocellular fatty acid synthesis by activating the PGE2-EP4 axis. Pharmacological inhibition of EP4 in HSC-specific Hic-5 overexpression mice fed with HFD diet (HFD) significantly attenuated NASH progression. These findings increase our understanding of molecular mechanisms linking hepatic lipid metabolism dysregulation and may offer therapeutic potential for treating NASH.PMID:41661520 | DOI:10.1186/s43556-026-00409-4

Chronic social defeat stress accelerates lung cancer progression and induces hippocampal metabolic dysregulation in a duration-optimized comorbid model

Mon, 09/02/2026 - 12:00
Metab Brain Dis. 2026 Feb 9;41(1):33. doi: 10.1007/s11011-026-01792-1.NO ABSTRACTPMID:41661484 | DOI:10.1007/s11011-026-01792-1

Overexpression of Chlorella ellipsoidea DGAT1 gene in soybean improves oil content and influences lipid metabolism

Mon, 09/02/2026 - 12:00
Planta. 2026 Feb 9;263(3):71. doi: 10.1007/s00425-026-04929-9.ABSTRACTOverexpression of Chlorella ellipsoidea DGAT1 in soybean increases oil content and changes the components of fatty acids in seeds, resulting a great influence on lipid metabolism. High oil transgenic soybean germplasm is important for expanding soybean breeding resources. Here, CeDGAT1, a gene from Chlorella ellipsoidea encoded a key rate-limiting enzyme in triacylglycerol synthesis, was introduced into soybeans by Agrobacterium-mediated soybean cotyledon node method, and we have obtained an overexpression line CeDGAT1-OE#7 based on soybean cultivar Dengke12. Firstly, qRT-PCR analyses displayed that CeDGAT1 was expressed in all the tissues of the transgenic line CeDGAT1-OE#7. And the total oil content was significantly higher by an average of 2.27% in seeds compared with the wild type. The analyses for the components of fatty acids showed that palmitic acid (16:0), stearic acids (18:0), and oleic acid (18:1) increased significantly by an average percentage of 1.34%, 0.62%, and 5.91%, respectively, while the contents of linoleic acid (18:2) and linolenic acids (18:3) were significantly lower than that of the WT. Furthermore, metabolomics analyses were conducted by using developing seeds of three stages, and a total of 1467, 1461, and 1078 significantly differentially expressed metabolites (DEMs) were separately identified. Two lipid-related pathways, linoleic acid metabolism and alpha-linolenic acid metabolism, were identified using KEGG pathway analysis of these DEMs, and seven metabolites in the linoleic acid metabolism pathway were down-regulated simultaneously, suggesting that these metabolites might be crucial in the response for overexpression of CeDGAT1. Together, our study has developed a high-oil transgenic soybean germplasm as a future breeding resource and those findings obtained from this research have broadened our understanding of the molecular mechanism underlying oil accumulation and fatty acid metabolism.PMID:41661319 | DOI:10.1007/s00425-026-04929-9

<em>Pseudomonas koreensis</em> HLG18 improves mulberry waterlogging resilience in riparian zone by synergistically modulating endophytic microbiome and metabolic profiles

Mon, 09/02/2026 - 12:00
Microbiol Spectr. 2026 Feb 9:e0295925. doi: 10.1128/spectrum.02959-25. Online ahead of print.ABSTRACTEndophytes play essential roles in protecting plants against abiotic stresses. However, whether and how they enhance waterlogging resilience in mulberry through changes in host-associated microbiota and metabolites remains unclear. Here, an endophytic bacterium strain HLG18, with plant growth promotion potential, was selected and identified as Pseudomonas koreensis HLG18. Genome analysis revealed that it possessed multiple genes involved in phytohormone biosynthesis, mineral dissolution, and stress adaptation. Greenhouse experiments consistently indicated that P. koreensis HLG18 significantly stimulated mulberry growth under waterlogging stress, accompanied by enhanced antioxidant enzyme activities and osmoprotectants. Amplicon sequencing revealed distinct endospheric microbiome profiles following HLG18 treatment, with notable changes in genera, such as Rhizorhapis, Bacillus, Caulobacter, and Rhodococcus. Meanwhile, soil potassium, phosphorus, and iron levels also differed. Correlation analyses indicated that the relative abundances of Rhizorhapis, Bacillus, Caulobacter, and Rhodococcus were significantly associated with soil properties and mulberry performance. Concurrently, metabolomic profiling revealed distinct metabolic signatures between treatments, including higher levels of stress-related metabolites (e.g., L-arginine, L-isoleucine) and differences in key metabolic pathways, such as tryptophan and purine metabolism. Overall, this study uncovers that P. koreensis HLG18 is linked to altered microenvironmental features and host metabolic patterns under waterlogging, providing new insights into endophyte-assisted plant stress adaptation.IMPORTANCEWaterlogging severely threatens the riparian zone of the Three Gorges Reservoir in China, causing extensive plant mortality and hindering restoration efforts. Mulberry is a promising candidate for ecological restoration, yet its growth is severely constrained under such conditions. Endophytes have emerged as key mediators of plant stress tolerance; however, their potential role in supporting mulberry adaptation to waterlogging in riparian zones remains largely unexplored. Our results show that the endophytic bacterium Pseudomonas koreensis HLG18 significantly promotes mulberry growth and enhances waterlogging tolerance. HLG18 inoculation is associated with distinct shifts in the host's endophytic microbiome, soil properties, and metabolite profiles, suggesting potential links to mulberry performance under waterlogging. Our findings highlight the potential of endophytes as bioinoculants to enhance mulberry waterlogging tolerance for ecological restoration in fragile riparian ecosystems and provide a valuable reference for harnessing beneficial microbial resources in sustainable agriculture under waterlogged conditions.PMID:41661001 | DOI:10.1128/spectrum.02959-25

Arsenic-Based Homeopathic Preparations Induce Metabolic Disruption and Reactive Oxygen Species-Mediated Cell Death in Glioblastoma Multiforme

Mon, 09/02/2026 - 12:00
Asian Pac J Cancer Prev. 2026 Feb 1;27(2):589-600. doi: 10.31557/APJCP.2026.27.2.589.ABSTRACTBACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive brain cancer with a poor median survival rate. There is an urgent need for effective and affordable anti-cancer agents for GBM treatment. In this context, arsenic-based homeopathic preparations may serve as promising therapeutic candidates.OBJECTIVES: This study aimed to evaluate the efficacy of Arsenicum iodatum and Arsenicum album-induced cytotoxicity in GBM cells and to investigate the underlying mechanisms of action in the U-87-MG and LN-229 cell lines.RESULTS: Treatment with varying concentrations of Arsenicum iodatum and Arsenicum album resulted in dose- and time-dependent inhibition of GBM cells growth in U87-MG and LN-229. These preparations induced distinct morphological changes and cell death in both GBM cell lines. Gas chromatography-mass spectrometry (GC-MS)-based metabolomics revealed significant alterations in the key metabolic pathways. A total of 107 metabolites were quantified. Univariate analysis identified 73 and 30 significantly altered metabolites in Arsenicum album-treated U-87-MG and LN-229 cells, respectively. Meanwhile, U-87 showed 69 and LN-229 showed 50 significantly affected metabolites in the Arsenicum iodatum-treated groups. In GBM cells treated with Arsenicum album and Arsenicum iodatum, glycine and serine, which are involved in redox balance, were altered, while branched-chain amino acids (valine, leucine, isoleucine)- essential for protein synthesis and mTOR signaling- were downregulated. Changes were also observed in nucleotide sugar, purine, and nicotinate/nicotinamide metabolism. The findings suggest that both agents cause strong metabolic disruptions, potentially contributing to their anti-cancer effects. Biochemical assays confirmed increased reactive oxygen species (ROS) levels and decreased mitochondrial membrane potential following treatment with these arsenic based homeopathic preparation.CONCLUSION: Arsenicum iodatum and Arsenicum album exhibit growth-inhibitory effects on GBM cells, likely through metabolic disruption and ROS-mediated cell death. Further studies are warranted to elucidate the precise mechanisms of cell death and to evaluate their efficacy and safety in vivo.PMID:41660917 | DOI:10.31557/APJCP.2026.27.2.589

Urinary Metabolomics Identifies Lactate as a Biomarker for Bladder Cancer Detection and Progression

Mon, 09/02/2026 - 12:00
Mol Omics. 2026 Feb 9:aaiag004. doi: 10.1093/molecular-omics/aaiag004. Online ahead of print.ABSTRACTBladder cancer (BC) is the ninth most prevalent malignancy worldwide. It remains a significant clinical burden due to high recurrence rates and the need for reliable non-invasive diagnostic tools. Metabolomics is a powerful strategy for non-invasive cancer detection, with urine representing an ideal biofluid for biomarker discovery given its direct contact with the urinary tract and its rich diversity of metabolites. This study aimed to identify urinary metabolites showing significant differences in urinary levels between BC patients and controls, and to evaluate their potential for diagnosis and disease monitoring. Beyond identifying metabolites differentiating BC patients from controls, we also assessed whether urinary metabolic patterns could distinguish BC subtypes (non-muscle invasive vs. muscle-invasive, NMIBC vs. MIBC). Following chemical derivatization, urinary samples were analysed by gas chromatography-mass spectrometry (GC-MS), and the resulting datasets were evaluated using univariate and multivariate statistical approaches. Among the 32 metabolites identified (e.g., amino acids, organic acids, alcohols, sugar-derivatives), lactate was identified as significantly upregulated in BC versus controls, particularly in MIBC cases. ROC analysis demonstrated good performance for overall BC detection and in discriminating between MIBC and NMIBC cases. These results, independent of smoking status and sex, position lactate as a promising non-invasive biomarker for invasive BC.PMID:41660878 | DOI:10.1093/molecular-omics/aaiag004

Metabolic engineering of <em>Corynebacterium glutamicum</em> for enhanced 5-aminolevulinic acid production via precise porphobilinogen synthase activity modulation

Mon, 09/02/2026 - 12:00
Appl Environ Microbiol. 2026 Feb 9:e0244725. doi: 10.1128/aem.02447-25. Online ahead of print.ABSTRACT5-Aminolevulinic acid (5-ALA) is a valuable precursor for pharmaceuticals and agriculture, but its microbial production is limited by tight coupling to essential heme biosynthesis. Here, we introduce a systematic, activity-graded tuning strategy for porphobilinogen synthase (PBGS, encoded by hemB) to decouple 5-ALA synthesis from heme metabolism in Corynebacterium glutamicum. Guided by structural and functional analyses, PBGS variants with progressively reduced activities were constructed to investigate the quantitative relationship between enzyme activity, cell growth, and 5-ALA accumulation. Controlled attenuation of PBGS activity maintained essential metabolism while markedly enhancing 5-ALA accumulation and minimizing porphyrin by-products. The engineered strain FA3 [hemB(D128E), hemA overexpression] achieved an optimal balance of growth and productivity. Metabolomic profiling confirmed that PBGS downregulation primarily suppressed porphyrin biosynthesis with minimal impact on central carbon metabolism. Subsequent metabolic and process optimizations, including gdhA and aceA deletion, dynamic rhtA expression, and cultivation control, further boosted production to 14.44 g/L 5-ALA in shake-flask culture, representing the highest shake-flask titer reported to our knowledge for C. glutamicum under similar conditions. This work provides the first systematic dissection of PBGS activity-dependent metabolic regulation and demonstrates that graded control of an essential enzyme enables rational metabolic decoupling, offering a broadly applicable framework for robust, high-yield microbial production of valuable compounds.IMPORTANCE5-Aminolevulinic acid (5-ALA) is an important precursor with pharmaceutical and agricultural applications, but microbial production is often constrained by its tight linkage to essential heme metabolism. Here, we systematically tuned porphobilinogen synthase activity to decouple 5-ALA accumulation from excessive porphyrin flux while maintaining cell growth. This strategy not only enabled the highest reported 5-ALA titer in Corynebacterium glutamicum but also highlights a broadly applicable framework for rationally engineering essential metabolic enzymes to achieve robust, high-yield microbial production of valuable compounds.PMID:41660829 | DOI:10.1128/aem.02447-25

Lifestyle-Associated Metabolic Signature Predicts the Risk of Amyotrophic Lateral Sclerosis

Mon, 09/02/2026 - 12:00
Muscle Nerve. 2026 Feb 9. doi: 10.1002/mus.70166. Online ahead of print.ABSTRACTINTRODUCTION/AIMS: Although the association between certain lifestyle factors and the risk of amyotrophic lateral sclerosis (ALS) has been recognized, the potential mechanism underlying it remains unexplored. This study aimed to identify the metabolic signature indicative of lifestyle factors related to ALS, to examine its association with ALS risk, and to evaluate the mediating effects of muscle strength underlying these associations.METHODS: This study used UK Biobank data, including ALS diagnoses, potential ALS-related factors, metabolomics, and hand grip strength. A total protective factor score was calculated from lifestyle data. Multivariable Cox regression analyzed associations between the score, its components, and ALS risk. ALS-related metabolic signatures were identified via elastic net regression. ALS risk across signature levels was compared by log-rank tests. Mediation analysis assessed the role of baseline hand grip strength.RESULTS: 248,222 participants were included in this study. Among lifestyle factors, the total protective factor score, no military service, and higher body mass index were significantly associated with reduced ALS risk. The metabolic signature derived from 163 metabolites indicative of potential ALS-associated protective factors was identified and found to be associated with lower ALS risk. Baseline hand grip strength of both hands was also associated with reduced ALS risk. Mediation analysis revealed that right-hand grip strength significantly mediated the associations between the total protective factor score, the metabolic signature, and ALS risk.DISCUSSION: Our study highlights the potential of the metabolic signature as a biomarker for early disease identification and underscores the importance of lifestyle-based prevention strategies.PMID:41660682 | DOI:10.1002/mus.70166

Integrated targeted metabolomics and transcriptomics analysis reveals heterogeneity of subcutaneous and pericardial adipose tissues in Yili horses

Mon, 09/02/2026 - 12:00
Food Chem (Oxf). 2026 Jan 26;12:100365. doi: 10.1016/j.fochms.2026.100365. eCollection 2026 Jun.ABSTRACTFat deposition is a key economic trait in livestock, yet distinct adipose depots often display marked functional heterogeneity. The molecular basis underlying this divergence in Yili horses, however, remains poorly understood. Therefore, we hypothesized that the heterogeneity in fatty acid composition between subcutaneous (SAT) and pericardial adipose tissues (PCAT) in Yili horses is associated with distinct transcriptional programs, which can be explored using an integrated multi-omics approach. Using targeted metabolomics, we found that PCAT contained significantly higher levels of total, saturated, and polyunsaturated fatty acids, but lower monounsaturated fatty acids (MUFAs) compared with SAT. Transcriptomic profiling identified 1513 differentially expressed genes (DEGs), which were primarily enriched in metabolic, endocrine, and signal transduction pathways. Integrative analysis further highlighted IGF1, LEP, BMP2, SOX9, COL1A2, and FGF9 as key regulators associated with depot-specific fatty acid differences. Collectively, these findings demonstrate the molecular heterogeneity between SAT and PCAT in Yili horses, support our original hypothesis, and provide a molecular basis for understanding adipose depot-specific lipid metabolism, with potential implications for improving fat deposition traits in Yili horses.PMID:41660677 | PMC:PMC12874588 | DOI:10.1016/j.fochms.2026.100365

Integrated transcriptomic and metabolomic profiling reveals sex-specific regulation of breast muscle development during sexual maturation in Huanglang chicken

Mon, 09/02/2026 - 12:00
Food Chem (Oxf). 2026 Jan 27;12:100366. doi: 10.1016/j.fochms.2026.100366. eCollection 2026 Jun.ABSTRACTTo better understand the regulatory mechanisms of breast muscle growth in small-sized local breeds, this study aimed to investigate metabolic and transcriptional networks during the initiation of sexual maturation in Huanglang chickens. We hypothesized that sex-specific metabolic and gene expression patterns regulate muscle growth and fat deposition in these chickens. To test this hypothesis, multi-omics approaches were used to analyze chickens at 80 and 120 days post-hatch (dph). Both male and female chickens showed a significant increase in intramuscular fat (IMF) at 120 dph, but with sex-specific changes: females exhibited a significantly higher liver index, while males had a significantly greater breast muscle index. We identified 2627 differentially expressed genes (DEGs) in males and 2991 in females, along with 473 and 232 differentially abundant metabolites (DAMs), respectively. The sex-shared ABC transporter pathway supports muscle growth via substrate transport, while the Steroid biosynthesis pathway is female-specific, and the Glycerophospholipid metabolism pathway is male-specific. These results demonstrate that sex-specific regulatory networks shape muscle growth and fat deposition during early sexual maturation, and they provide potential molecular targets for improving intramuscular fat content and meat quality in local chicken breeding programs.PMID:41660676 | PMC:PMC12878698 | DOI:10.1016/j.fochms.2026.100366

Lychee peel extract and chitosan synergistically delay mango ripening: Molecular insights

Mon, 09/02/2026 - 12:00
Food Chem (Oxf). 2026 Jan 13;12:100355. doi: 10.1016/j.fochms.2026.100355. eCollection 2026 Jun.ABSTRACTAlthough lychee peel extract (LPE) is rich in bioactive compounds, its potential for postharvest fruit preservation remains unexplored. We hypothesised that LPE would act synergistically with chitosan (CH) to delay mango ripening by simultaneously modulating cell wall integrity, pigment metabolism, and hormone signaling pathways. Here, we demonstrate that chitosan combined with lychee peel extract (CHL) delays mango ripening through a multi-targeted mechanism. Specifically, CHL outperformed chitosan alone by significantly suppressing peel yellowing, maintaining fruit firmness, and reducing decay over 12 days of storage. Integrated transcriptomic and metabolomic analyses revealed that LPE reprogrammed ripening-associated pathways by (1) upregulating cell wall remodeling genes (CSLE1, XTH23) to stabilize pectin architecture, (2) retaining chlorophyll via suppressed CRTISO and PSY (carotenoid synthesis) and enhanced CHLP (chlorophyll biosynthesis), and (3) decoupling sugar-acid dynamics through γ-aminobutyric acid (GABA) and succinic acid accumulation. Notably, LPE attenuated ethylene-auxin- abscisic acid (ABA) crosstalk by downregulating ripening-specific transcription factors (ERF003, bZIPs) while activating stress-responsive WRKYs. These findings establish LPE as a sustainable alternative to synthetic preservatives, leveraging agricultural byproducts for eco-friendly fruit preservation.PMID:41660675 | PMC:PMC12874597 | DOI:10.1016/j.fochms.2026.100355

Hypermetabolism and Lipid Alterations Postburn: A Cardiovascular Perspective

Mon, 09/02/2026 - 12:00
Cardiovasc Ther. 2026 Feb 6;2026:5983391. doi: 10.1155/cdr/5983391. eCollection 2026.ABSTRACTSevere thermal burns involving ≥ 20% of total body surface area (TBSA) initiate a distinct, prolonged physiological cascade extending well beyond the acute phase. This dysregulated response features chronic hypermetabolism, lipid remodeling, and sustained cardiovascular stress. While survival has improved with advances in acute care, the long-term cardiometabolic effects, particularly the link between lipid abnormalities and cardiovascular risk, remain underexplored. This review highlights the complex pathophysiology of burn-induced hypermetabolism, including elevated resting energy expenditure, catecholamine-driven lipolysis, mitochondrial uncoupling, and maladaptive adipose browning. Even in metabolically healthy individuals, these mechanisms promote atherogenic dyslipidemia, characterized by hepatic steatosis, elevated small-dense LDL, reduced HDL-C, and persistent hypertriglyceridemia. Emerging lipidomic and clinical data correlate these changes with increased Framingham risk scores, systemic inflammation, and TBSA extent. Simultaneously, cardiovascular vulnerability increases due to myocardial remodeling, autonomic dysfunction, and vascular impairment, particularly in young survivors with prolonged metabolic responses. Imaging and metabolomics reveal endothelial injury, subclinical cardiac dysfunction, and elevated arrhythmogenic risk persisting years after healing. We evaluate current interventions, β-blockers, omega-3 fatty acids, statins, anti-inflammatory agents, and structured rehabilitation, within a multimodal framework. Additionally, we identify critical gaps, including the need for precision metabolic modulation, omics-based monitoring, and tailored cardiovascular risk algorithms. Recognizing severe burns as systemic illnesses with delayed but measurable cardiovascular consequences requires a paradigm shift in long-term care. This review advocates for proactive, multidisciplinary cardiometabolic surveillance as an essential component of postburn recovery. This review follows the TITAN 2025 guideline for transparency in research and reporting.1.PMID:41660577 | PMC:PMC12878538 | DOI:10.1155/cdr/5983391

Multi-omics reveals the protective mechanisms of <em>Gastrodia elata</em> ethyl acetate extract in vascular dementia

Mon, 09/02/2026 - 12:00
Front Pharmacol. 2026 Jan 23;17:1630783. doi: 10.3389/fphar.2026.1630783. eCollection 2026.ABSTRACTOBJECTIVE: This study aimed to investigate the ameliorative effect of the ethyl acetate extract of Gastrodia elata (EEGE) on vascular dementia (VD) and its underlying mechanisms.METHODS: A VD rat model was established using the two-vessel occlusion method, while an in vitro cerebral ischemia injury model was constructed by subjecting HT22 cells to oxygen-glucose deprivation. The mechanisms were systematically explored through behavioral tests, ELISA, integrated network analysis, and combined metabolomic and transcriptomic techniques. Key targets were further validated by Western blot.RESULTS: EEGE significantly improved cognitive function in VD rats. Integrated multi-omics and network analysis predicted that its effects involved two key targets, TNF and IGF1, and identified Parishin A and p-hydroxybenzaldehyde as prioritized drug metabolites for assessment. Subsequent experiments confirmed that EEGE effectively downregulated serum levels of IL-6, TNF-α, and IL-1β by modulating the IGF1-TREM2 signaling axis and the AMPK-SIRT1-FoxO1-NF-κB pathway.CONCLUSION: The improvement of cognitive dysfunction in vascular dementia by EEGE is closely associated with its regulation of the IGF1-TREM2 axis and the AMPK-SIRT1-FoxO1-NF-κB pathway, thereby mitigating neuroinflammation. This study provides experimental evidence and a potential mechanistic basis for further exploration of EEGE in VD intervention.PMID:41660514 | PMC:PMC12876206 | DOI:10.3389/fphar.2026.1630783

Comparative metabolomics reveals organ-specific discrepancy in TCMSP-predicted bioactive ingredients between two geographically distinct regions of Rehmannia chingii

Mon, 09/02/2026 - 12:00
PeerJ. 2026 Feb 3;14:e20722. doi: 10.7717/peerj.20722. eCollection 2026.ABSTRACTBACKGROUND: The geographical region and organ-specific accumulation of metabolites in medicinal plants are critical determinants of their pharmaceutical efficacy. Rehmannia chingii, an endemic species native to eastern China and a significant member of the genus Rehmannia, exhibits multiple bioactive properties in both its leaves and roots. However, spatial distribution of its pharmaceutical ingredients across various geographical regions remains inadequately understood.METHODS AND RESULTS: This study combined widely targeted metabolomics with the Traditional Chinese Medicine System Drug Analysis Platform (TCMSP) to investigate the accumulation patterns of medicinal ingredients in the leaves and roots of fresh R. chingii from two distinct geographical regions. Among the 1,420 metabolites identified, four differential biomarkers were identified: p-coumaroylcadaverine and protocatechuic acid-4-o-glucoside, which were primarily associated with geographical differentiation, and 5, 6-dimethyl-2-benzofuran-1, 3-dione and daphnin, which were indicative of organ type classification. Additionally, 31 potential bioactive ingredients were prioritized via TCMSP screening. Metabolic profiling further revealed that multiple flavonoids were enriched in leaves, whereas roots accumulated higher levels of tangeretin, 6-o-p-coumaroylajugol, guanosine, virexilactone, and aucubin. Notably, coniferin and tangeretin, with oral bioavailability values ≥30% and drug-likeness values ≥0.18, were identified as key potential bioactive marker ingredients, and they were highly abundant in R. chingii from the Tianmu Mountain region of Hangzhou.CONCLUSION: These findings highlight the critical role of geographic and organ-specific factors in determining the metabolic profiles of R. chingii, thereby advancing our understanding of its medicinal value and providing a theoretical basis for the rational exploitation and utilization of its medicinal resources.PMID:41660092 | PMC:PMC12880092 | DOI:10.7717/peerj.20722

On-farm dietary supplementation of black seed (Nigella sativa) meal in goats: effects on physiological and metabolomic responses during transportation

Mon, 09/02/2026 - 12:00
Front Vet Sci. 2026 Jan 22;12:1721007. doi: 10.3389/fvets.2025.1721007. eCollection 2025.ABSTRACTBlack cumin or black seed (Nigella sativa) has many beneficial biological properties, and its processing for oil extraction produces a byproduct known as black seed meal (BSM), which is utilized as an animal feed supplement. An experiment was conducted on a commercial farm to determine the effects of BSM supplementation and long-duration transportation on stress and metabolomic responses and antioxidant and immune capacities in goats. Ninety-six uncastrated male Spanish goats (4-5 months old) were randomly divided into two treatment (TRT) groups. Forty-eight goats were fed a concentrate diet containing 15% BSM, and 48 goats were fed the same diet with no BSM (control, C) in separate corrals for 3 weeks with ad libitum water. On the day of the experiment, goats were loaded onto two identical trailers (5 × 2.3 m), with 40 goats/trailer (20 goats/TRT), and were transported for 16 h to simulate a commercial situation. Blood samples were collected at 0 h (15 min after loading), 2 h, 4 h, 10 h, and 16 h of transportation (Time; n = 8 goats/Time/TRT) by jugular venipuncture. The dietary BSM supplementation in goats did not affect stress responses, except for tyramine (p < 0.05), but Time significantly affected (p < 0.05) plasma epinephrine, metanephrine, and normetanephrine. The BSM supplement did not significantly affect the antioxidant and immune status variables. At the metabolome level, 15 amino acids, 4 acylcarnitines, 24 phosphatidylcholines and sphingomyelins, and 13 other metabolites were significantly affected (p < 0.05) by TRT. Acylcarnitine (C2), hexadecenoylcarnitine (C16:1), hydroxybutyrylcarnitine (C4OH), β-hydroxybutyric acid, and iso-butyric acid concentrations were higher (p < 0.05) in the BSM goats, indicating energy supply was mainly through lipid metabolism. The BSM group had lower (p < 0.05) concentrations of glucose, 11 of the amino acids, and TCA cycle metabolites compared to the C group. Supplementation of BSM in the meat goat diet prior to extended road transportation may help them use fat as an energy source instead of breaking down protein. However, at a 15% level, there were no significant effects on antioxidant and immune status indicators determined.PMID:41659958 | PMC:PMC12872573 | DOI:10.3389/fvets.2025.1721007

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