PubMed

Hepatology. 2025 Mar 12. doi: 10.1097/HEP.0000000000001304. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Portal vein tumor thrombosis (PVTT), an indicator of clinical metastasis, significantly shortens hepatocellular carcinoma (HCC) patients' lifespan, and no effective treatment has been established. We aimed to illustrate mechanisms underlying PVTT formation and tumor metastasis, and identified potential targets for clinical intervention.APPROACH AND RESULTS: Multi-omics data of 159 HCC patients (including 37 cases with PVTT) was analyzed to identify contributors to PVTT formation and tumor metastasis. In vitro and in vivo experiments were performed to confirm the critical role of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) in HCC metastasis. Metabolomics and transcriptomics techniques, single-cell RNA sequencing, combined with experimental verification were complemented to illustrate mechanisms underlying CAD induced pro-metastatic efficacy. Analysis of proteogenomic data of HCC cohort identified CAD as the key contributor to PVTT formation and tumor metastasis in HCC. Further experiments confirmed that high CAD expression could significantly promote HCC metastasis, and vice versa. Mechanistically, CAD manipulated de novo pyrimidine anabolism, leading to dihydroorotic acid (DHO) accumulation which directly bound to ubiquitination factor E4B (UBE4B). UBE4B subsequently regulated JAK1 ubiquitination and activated the NF-κB pathway to promote epithelial-mesenchymal transition (EMT) of HCC cells. Additionally, CAD generated an immunosuppressive milieu conducive to HCC metastasis by recruiting and reprogramming macrophages into a "pro-tumor" phenotype. Consequently, the metastatic capability of HCC was remarkably enhanced.CONCLUSION: Therapy targeting CAD may offer a promising approach to curb HCC metastasis by reducing tumor cells' metastatic potential and also shifting the tumor microenvironment towards a less pro-metastatic state.PMID:40073276 | DOI:10.1097/HEP.0000000000001304

J Proteome Res. 2025 Mar 12. doi: 10.1021/acs.jproteome.4c00529. Online ahead of print.ABSTRACTLung cancer stands as the leading cause of cancer-related death worldwide, impacting both men and women in the United States and beyond. Radiation therapy (RT) serves as a key treatment modality for various lung malignancies. Our study aims to systematically assess the prognosis and influence of RT on metabolic reprogramming in patients diagnosed with nonsmall-cell lung cancer (NSCLC) through longitudinal metabolic profiling. A cohort of 54 NSCLC patients underwent thoracic radiotherapy, with 96% receiving a total radiation dose ranging from 40 to 70 Gy, averaging 56.3 Gy. Blood biospecimens were collected before RT, during RT, and at the first follow-up after RT, with a total of 126 serum samples randomized for liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis using a high-performance LC (HPLC)-Q-Exactive mass spectrometry system. Our results indicated that the serum metabolite coumarin derivatives prior to radiotherapy exhibited the strongest unfavorable outcome with overall survival in these NSCLC cases. The metabolites in the blood samples can reflect the responses during RT. Notably, over half of the metabolites (12/23) were found to be fatty acids in the longitudinal analysis. This pilot study indicated that metabolic profiling of biofluids from NSCLC patients undergoing RT has the potential to assess the patient outcomes during and after treatment.PMID:40073233 | DOI:10.1021/acs.jproteome.4c00529

Br Poult Sci. 2025 Mar 12:1-10. doi: 10.1080/00071668.2025.2454960. Online ahead of print.ABSTRACT1. The avian gut hosts a complex and dynamic microbial ecosystem, which is essential for regulating host organ function. However, the relationship between the gut microbiota and the hypothalamic axis in acute stress vulnerability in ducks remains unclear.2. This study investigated how the gut microbiota affects microbial metabolism and the host stress response by comparing hypothalamic neurotransmitter availability, microbial composition and co-metabolites generated by both the microbiota and hypothalamus in ducks exhibiting the lowest active avoidance (LAA) and highest active avoidance (HAA) behaviour.3. The HAA group experienced a significant increase in the availability of arginine, histidine, glutamine, norepinephrine, L-tyrosine and melatonin during acute stress in the hypothalamus, compared to that in the LAA group. The 16S rRNA sequencing revealed significant differences in the gut microbiota composition based on acute stress vulnerabilities.4. Both caecal and hypothalamic metabolomic analyses identified 71 metabolites altered in caecal content and 95 in the hypothalamus. There was significant enrichment in pathways such as the cGMP-PKG signalling, dopaminergic synapse and endocrine resistance.5. Correlation analyses demonstrated that certain co-metabolites, including 1,3-dicyclohexylurea, 1-deoxyvaleric acid, 2-amino-2-methyl-1,3-propanediol, 3-chloroaniline, methenamine, N4-acetylcytidine-triphosphate and traumatin, may play a role in the gut microbiota-hypothalamic axis.6. The results suggested that the gut microbiome influenced acute stress responses. This provided a basis for understanding gut-hypothalamic communication and its impact on behaviour in ducks.PMID:40072466 | DOI:10.1080/00071668.2025.2454960

Cells. 2025 Mar 2;14(5):367. doi: 10.3390/cells14050367.ABSTRACTThis study investigates the metabolic responses of cancerous (RCC) and non-cancerous (HK2) kidney cells to treatment with Staurosporine (STAU), which has a pro-apoptotic effect, and Bongkrekic acid (BKA), which has an anti-apoptotic effect, individually and in combination, using 1H NMR metabolomics to identify metabolite markers linked to mitochondrial apoptotic pathways. BKA had minimal metabolic effects in RCC cells, suggesting its role in preserving mitochondrial function without significantly altering metabolic pathways. In contrast, STAU induced substantial metabolic reprogramming in RCC cells, disrupting energy production, redox balance, and biosynthesis, thereby triggering apoptotic pathways. The combined treatment of BKA and STAU primarily mirrored the effects of STAU alone, with BKA showing little capacity to counteract the pro-apoptotic effects. In non-cancerous HK2 cells, the metabolic alterations were far less pronounced, highlighting key differences in the metabolic responses of cancerous and non-cancerous cells. RCC cells displayed greater metabolic flexibility, while HK2 cells maintained a more regulated metabolic state. These findings emphasize the potential for targeting cancer-specific metabolic vulnerabilities while sparing non-cancerous cells, underscoring the value of metabolomics in understanding apoptotic and anti-apoptotic mechanisms. Future studies should validate these results in vivo and explore their potential for personalized treatment strategies.PMID:40072095 | DOI:10.3390/cells14050367

Cells. 2025 Feb 28;14(5):361. doi: 10.3390/cells14050361.ABSTRACTAn association between gut microbiota and the development of pancreatic ductal adenocarcinoma (PDAC) has been previously described. To better understand the bacterial microbiota changes accompanying PDAC promotion and progression stimulated by inflammation and fecal microbiota transplantation (FMT), we investigated stool and pancreatic microbiota by 16s RNA-based metagenomic analysis in mice with inducible acinar transgenic expressions of KrasG12D, and age- and sex-matched control mice that were exposed to inflammatory stimuli and fecal microbiota obtained from mice with PDAC. Time- and inflammatory-dependent stool and pancreatic bacterial composition alterations and stool alpha microbiota diversity reduction were observed only in mice with a Kras mutation that developed advanced pancreatic changes. Stool Actinobacteriota abundance and pancreatic Actinobacteriota and Bifidobacterium abundances increased. In contrast, stool abundance of Firmicutes, Verrucomicrobiota, Spirochaetota, Desulfobacterota, Butyricicoccus, Roseburia, Lachnospiraceae A2, Lachnospiraceae unclassified, and Oscillospiraceae unclassified decreased, and pancreatic detection of Alloprevotella and Oscillospiraceae uncultured was not observed. Furthermore, FMT accelerated tumorigenesis, gradually decreased the stool alpha diversity, and changed the pancreatic and stool microbial composition in mice with a Kras mutation. Specifically, the abundance of Actinobacteriota, Bifidobacterium and Faecalibaculum increased, while the abundance of genera such as Lachnospiraceace A2 and ASF356, Desulfovibrionaceace uncultured, and Roseburia has decreased. In conclusion, pancreatic carcinogenesis in the presence of an oncogenic Kras mutation stimulated by chronic inflammation and FMT dynamically changes the stool and pancreas microbiota. In particular, a decrease in stool microbiota diversity and abundance of bacteria known to be involved in short-fatty acids production were observed. PDAC mouse model can be used for further research on microbiota-PDAC interactions and towards more personalized and effective cancer therapies.PMID:40072088 | DOI:10.3390/cells14050361

Scand J Med Sci Sports. 2025 Mar;35(3):e70034. doi: 10.1111/sms.70034.ABSTRACTHigh cardiorespiratory fitness (CRF) is associated with better overall health. This study aimed to find a metabolic signature associated with CRF to identify health-promoting effects. CRF based on cardiopulmonary exercise testing, targeted and untargeted metabolomics approaches based on mass spectrometry, and clinical data from two independent cohorts of the Study of Health in Pomerania (SHIP) were used. Sex-stratified linear regression models were adjusted for age, smoking, and height to relate CRF with individual metabolites. A total of 132 (SHIP-START-2: 483 men with a median age of 58 years and 450 women with a median age of 56 years) and 118 (SHIP-TREND-0: 341 men and 371 women both with a median age of 51 years) metabolites were associated with CRF. Lipids showed bidirectional relations to CRF independent of sex. Specific subsets of sphingomyelins were positively related to CRF in men (SM (OH) C14:1, SM(OH)C22:2 SM C16:0, SM C20:2 SM(OH)C24:1) and inversely in women (SM C16:1, SM C18:0, SM C18:1). Metabolites involved in energy production (citrate and succinylcarnitine) were only associated with CRF in men. In women, xenobiotics (hippurate, stachydrine) were related to CRF. The sex-specific metabolic signature of CRF is influenced by sphingomyelins, energy substrates, and xenobiotics. The greater effect estimates seen in women may emphasize the important role of CRF in maintaining metabolic health. Future research should explore how this profile changes with different types of exercise interventions or diseases in diverse populations and how these metabolites could be implemented in primary prevention settings.PMID:40072034 | DOI:10.1111/sms.70034

Immunol Rev. 2025 Mar;330(1):e70015. doi: 10.1111/imr.70015.ABSTRACTAsthma is one of the most prevalent and extensively studied chronic respiratory conditions, yet the heterogeneity of asthma remains biologically puzzling. Established factors like exogenous exposures and treatment adherence contribute to variability in asthma risk and clinical outcomes. It is also clear that the endogenous factors of genetics and immune system response patterns play key roles in asthma. Despite significant existing knowledge in the above, divergent clinical trajectories and outcomes are still observed, even among individuals with similar risk profiles, biomarkers, and optimal medical management. This suggests uncaptured biological interactions that contribute to asthma's heterogeneity, for which the role of host microbiota has lately attracted much research attention. This review will highlight recent evidence in this area, focusing on bedside-to-bench investigations that have leveraged omic technologies to uncover microbiome links to asthma outcomes and immunobiology. Studies centered on the respiratory system and the use of multi-omics are noted in particular. These represent a new generation of reverse-translational investigations revealing potential functional crosstalk in host microbiomes that may drive phenotypic heterogeneity in chronic diseases like asthma. Multi-omic data offer a wide lens into ecosystem interactions within a host. This informs new hypotheses and experimental work to elucidate mechanistic pathways for unresolved asthma endotypes. Further incorporation of multi-omics into patient-centered investigations can yield new insights that hopefully lead to even more precise, microbiome-informed strategies to reduce asthma burden.PMID:40072031 | DOI:10.1111/imr.70015

Gut Microbes. 2025 Dec;17(1):2476562. doi: 10.1080/19490976.2025.2476562. Epub 2025 Mar 12.ABSTRACTThe gut microbiome is known to have a bidirectional relationship with sex hormone homeostasis; however, its role in mediating interactions between the primary regulatory axes of sex hormones and their productions is yet to be fully understood. We utilized both conventionally raised and gnotobiotic mouse models to investigate the regulatory role of the gut microbiome on the hypothalamic-pituitary-gonadal (HPG) axis. Male and female conventionally raised mice underwent surgical modifications as follows: (1) hormonally intact controls; (2) gonadectomized males and females; (3) gonadectomized males and females supplemented with testosterone and estrogen, respectively. Fecal samples from these mice were used to colonize sex-matched, intact, germ-free recipient mice through fecal microbiota transplant (FMT). Serum gonadotropins, gonadal sex hormones, cecal microbiota, and the serum global metabolome were assessed. FMT recipients of gonadectomized-associated microbiota showed lower circulating gonadotropin levels than recipients of intact-associated microbiota, opposite to that of FMT donors. FMT recipients of gonadectomized-associated microbiota also had greater testicular weights compared to recipients of intact-associated microbiota. The gut microbiota composition of recipient mice differed significantly based on the FMT received, with the male microbiota having a more concerted impact in response to changes in the HPG axis. Network analyses showed that multiple metabolically unrelated pathways may be involved in driving differences in serum metabolites due to sex and microbiome received in the recipient mice. In sum, our findings indicate that the gut microbiome responds to the HPG axis and subsequently modulates its feedback mechanisms. A deeper understanding of interactions between the gut microbiota and the neuroendocrine-gonadal system may contribute to the development of therapies for sexually dimorphic diseases.PMID:40071861 | DOI:10.1080/19490976.2025.2476562

J Exp Bot. 2025 Mar 12:eraf116. doi: 10.1093/jxb/eraf116. Online ahead of print.ABSTRACTPlant metabolism is profoundly affected by various abiotic stresses. Consequently, plants must reconfigure their metabolic networks to sustain homeostasis while synthesizing compounds that mitigate stress. This aspect, with the current intensified climate impact results in more frequent abiotic stresses on a global scale. Advances in metabolomics and systems biology in the last decades have enabled both a comprehensive overview and a detailed analysis of key components involved in the plant metabolic response to abiotic stresses. This review addresses metabolic responses to altered atmospheric CO2 and O3, water deficit, temperature extremes, light intensity fluctuations including the importance of UV-B, ionic imbalance, and oxidative stress predicted to be caused by climate change, long-term shifts in temperatures and weather patterns. It also assesses both the commonalities and specificities of metabolic responses to diverse abiotic stresses, drawing on data from the literature. Classical stress-related metabolites such as proline, and polyamines are revisited, with an emphasis on the critical role of branched-chain amino acid metabolism under stress conditions. Finally, where possible, mechanistic insights into the regulation of metabolic processes and further outlook on combinatory stresses are discussed.PMID:40071778 | DOI:10.1093/jxb/eraf116

J Am Chem Soc. 2025 Mar 12;147(10):8672-8686. doi: 10.1021/jacs.4c18110. Epub 2025 Mar 2.ABSTRACTAccurate diagnosis of early gastric cancer is valuable for asymptomatic populations, while current endoscopic examination combined with pathological tissue biopsy often encounters bottlenecks for early-stage cancer and causes pain to patients. Liquid biopsy shows promise for noninvasive diagnosis of early gastric cancer; however, it remains a challenge to achieve accurate diagnosis due to the lack of highly sensitive and specific biomarkers. Herein, we propose a protocol combining metabolomics profiling from plasma extracellular vesicles (EVs) and machine learning to identify the metabolomics discrepancies of early gastric cancer individuals from other populations. Efficient metabolomics profiling is achieved by efficient, high-purity, and damage-free plasma EVs separation using elaborately designed nanotrap-structured microparticles (NanoFisher) by taking advantage of stereoscopic interaction and affinity interaction. Significant metabolomics discrepancies are obtained from 150 early gastric cancer (50), benign gastric disease (50), and non-disease control (50) plasma samples. Machine learning enables ideal distinction between early gastric cancer and non-disease control samples with an area under the curve (AUC) of 1.000, achieves an AUC of 0.875-0.975 for differentiating early gastric cancer from benign gastric diseases, and demonstrates an overall accuracy of 92% in directly classifying these three categories. The plasma EV metabolomics profiling enabled by NanoFisher materials, integrated with machine learning, holds considerable promise for broad clinical acceptance, enhancing gastric cancer screening outcomes.PMID:40071449 | DOI:10.1021/jacs.4c18110

Curr Opin Oncol. 2025 Mar 12. doi: 10.1097/CCO.0000000000001137. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: This review examines the existing literature on metabolic pathways associated with bladder cancer (BC) and investigates four domains: (1) diagnoses, (2) cancer classification (staging & grading), (3) tracking, and (4) treatment.RECENT FINDINGS: A systematic search of relevant databases identified studies meeting predefined inclusion criteria. A diverse array of metabolic pathways was found to hold significant biological and clinical relevance to BC, with particular emphasis on amino acid (AA), lipid, nucleic acid (NA), and bioenergetic pathways. Recent studies have elucidated utilities for metabolomics in diagnosis of BC, staging and grading the disease, monitoring progression or recurrence, and informing treatment strategies. Specifically, fatty acids were observed to be upregulated by as much as 90-fold in studies focused on BC diagnosis, alongside the upregulation of AA metabolites. Metabolites such as AA, lipids, and aldehydes showed potential as diagnostic biomarkers for BC. NA metabolites were particularly effective in monitoring BC status postsurgical resection. Furthermore, metabolites from lipid, bioenergetic, and AA pathways demonstrated utility in predicting tumor cell sensitivity to chemotherapy.SUMMARY: A broad spectrum of metabolic pathways and metabolites offers significant potential for applications in the diagnosis, staging, monitoring, and treatment of BC. These findings underscore the promise of metabolomics as a valuable tool in improving BC management and patient outcomes.PMID:40071441 | DOI:10.1097/CCO.0000000000001137

Circulation. 2025 Mar 12. doi: 10.1161/CIRCULATIONAHA.124.070248. Online ahead of print.ABSTRACTBACKGROUND: Despite the high morbidity and mortality of heart failure with preserved ejection fraction (HFpEF), treatment options remain limited. The HFpEF syndrome is associated with a high comorbidity burden, including high prevalence of obesity and hypertension. Although inflammation is implicated to play a key role in HFpEF pathophysiology, underlying causal mechanisms remain unclear.METHODS: Comparing patient samples and animal models, we defined the innate immune response during HFpEF in situ and through flow cytometry and single-cell RNA sequencing. After identifying transcriptional and cell signatures, we implemented a high-fat diet and hypertensive model of HFpEF and tested roles for myeloid and hematopoietic stem cells during HFpEF. Contributions of macrophage metabolism were also evaluated, including through mass spectrometry and carbon labeling. Primary macrophages were studied ex vivo to gain insight into complementary cell-intrinsic mechanisms.RESULTS: Here we report evidence that patients with cardiometabolic HFpEF exhibit elevated peripheral blood hematopoietic stem cells. This phenotype was conserved across species in a murine mode of high-fat diet and hypertension. Hematopoietic stem cell proliferation was coupled to striking remodeling of the peripheral hematopoietic stem cell niche and expression of the macrophage adhesion molecule Vcam1. This could be partially inhibited by sodium-glucose cotransporter-2 inhibitors and explained by elevated fatty acid metabolism in macrophage mitochondria, which in turn remodeled the Vcam1 promoter to enhance its expression.CONCLUSIONS: These findings identify a significant new stem cell signature of cardiometabolic HFpEF and support a role for myeloid maladaptive fatty acid metabolism in the promotion of systemic inflammation and cardiac diastolic dysfunction.PMID:40071347 | DOI:10.1161/CIRCULATIONAHA.124.070248

Circulation. 2025 Mar 12. doi: 10.1161/CIRCULATIONAHA.124.067876. Online ahead of print.ABSTRACTBACKGROUND: Cardiac β3-adrenergic receptors (ARs) are upregulated in diseased hearts and mediate antithetic effects to those of β1AR and β2AR. β3AR agonists were recently shown to protect against myocardial remodeling in preclinical studies and to improve systolic function in patients with severe heart failure. However, the underlying mechanisms remain elusive.METHODS: To dissect functional, transcriptional, and metabolic effects, hearts and isolated ventricular myocytes from mice harboring a moderate, cardiac-specific expression of a human ADRB3 transgene (β3AR-Tg) and subjected to transverse aortic constriction were assessed with echocardiography, RNA sequencing, positron emission tomography scan, metabolomics, and metabolic flux analysis. Subsequently, signaling and metabolic pathways were further investigated in vivo in β3AR-Tg and ex vivo in neonatal rat ventricular myocytes adenovirally infected to express β3AR and subjected to neurohormonal stress. These results were complemented with an analysis of single-nucleus RNA-sequencing data from human cardiac myocytes from patients with heart failure.RESULTS: Compared with wild-type littermates, β3AR-Tg mice were protected from hypertrophy after transaortic constriction, and systolic function was preserved. β3AR-expressing hearts displayed enhanced myocardial glucose uptake under stress in the absence of increased lactate levels. Instead, metabolomic and metabolic flux analyses in stressed hearts revealed an increase in intermediates of the pentose-phosphate pathway in β3AR-Tg, an alternative route of glucose utilization, paralleled with increased transcript levels of NADPH-producing and rate-limiting enzymes of the pentose-phosphate pathway, without fueling the hexosamine metabolism. The ensuing increased content of NADPH and of reduced glutathione decreased myocyte oxidant stress, whereas downstream oxidative metabolism assessed by oxygen consumption was preserved with higher glucose oxidation in β3AR-Tg mice after transaortic constriction compared with wild type, together with increased mitochondrial biogenesis. Unbiased transcriptomics and pathway analysis identified NRF2 (NFE2L2) as an upstream transcription factor that was functionally verified in vivo and in β3AR-expressing cardiac myocytes, where its translocation and nuclear activity were dependent on β3AR activation of nitric oxide synthase and nitric oxide production through S-nitrosation of the NRF2-negative regulator Keap1.CONCLUSIONS: Moderate expression of cardiac β3AR, at levels observed in human cardiac myocardium, exerts metabolic and antioxidant effects through activation of the pentose-phosphate pathway and NRF2 pathway through S-nitrosation of Keap1, thereby preserving myocardial oxidative metabolism, function, and integrity under pathophysiological stress.PMID:40071326 | DOI:10.1161/CIRCULATIONAHA.124.067876

Front Psychiatry. 2025 Feb 25;16:1446897. doi: 10.3389/fpsyt.2025.1446897. eCollection 2025.ABSTRACTINTRODUCTION: Previous studies have found that depressive patients tend to have low levels of creatinine; however, the extent to which creatinine levels are associated with depression has been poorly investigated. Therefore, this study aimed to explore the relationship between creatinine levels and depression.METHODS: The participants and follow-up data from the China Health and Retirement Longitudinal Study (CHARLS), as well as metabolomics data from the Metabolite Network of Depression Database (MENDA), were collected. The 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) was used to assess the severity of depression. Spearman correlation analysis, spline regression, and binary logistic regression models were employed to explore the relationship between creatinine levels and depression.RESULTS: A total of 7,826 participants and 3,886 follow-up participants were included in the CHARLS 2011 and 2015 surveys. Of these, 37.9% (2,966/7,826) and 34.6% (13,44/3,886) of participants experienced depression in CHARLS 2011 and 2015, respectively. The creatinine level was negatively correlated with the total CESD-10 score and dimensions scores, showing an inverse dose-response relationship between creatinine levels and depression. Compared with participants with high creatinine levels, those with middle creatinine levels were associated with a higher risk of depression (OR = 1.22, 95% CI = 1.08-1.38), while participants with low creatinine levels had the highest risk of depression (OR = 1.30, 95% CI = 1.13-1.49) in the fully adjusted model. Similar results were observed in the follow-up data, and the MENDA metabolomics data validated the negative correlation between creatinine levels and the severity of depression.CONCLUSION: Lower levels of creatinine were closely associated with a higher risk of depression, and it could serve as a potential marker for identifying individuals at high risk of depression.PMID:40071279 | PMC:PMC11894454 | DOI:10.3389/fpsyt.2025.1446897

Front Microbiol. 2025 Feb 25;16:1509548. doi: 10.3389/fmicb.2025.1509548. eCollection 2025.ABSTRACTOBJECTIVE: To investigate the relationship between heart failure (HF) and gut microbiota-mediated energy metabolism, and to explore the role of Shenfu Injection in this process.MATERIALS AND METHODS: In this study, Adriamycin-induced chronic heart failure (CHF) rat model was used and randomly divided into the blank control group (Normal, n = 9), HF control group (Model, n = 12), Shenfu Injection treatment group (SFI, n = 9), and positive drug control group (TMZ, n = 9). The changes in gut microbiota structure were analyzed by 16S rRNA high-throughput sequencing, the content of short-chain fatty acids (SCFAs) was detected by targeted metabolomics technology, and cardiac function and energy metabolism-related indicators were evaluated.RESULTS: Myocardial energy metabolism in HF rats was disordered, characterized by reduced fatty acid oxidation, enhanced anaerobic glycolysis of glucose, mitochondrial damage, and decreased ATP content; The gut microbiota of HF rats was imbalanced, with a reduction in beneficial bacteria, an increase in conditional pathogenic bacteria, and impaired intestinal barrier function; Both Shenfu Injection and trimetazidine improved myocardial energy metabolism and cardiac function, but Shenfu Injection was more significant in regulating gut microbiota and improving intestinal health; The production of SCFAs from the gut microbiota of HF rats increased, which may be closely related to myocardial energy metabolism; SCFAs-producing bacteria Akkermansia and Blautia played a key role in the development of HF, and their abundance was positively correlated with SCFAs content.CONCLUSION: Shenfu Injection in treating HF may improve myocardial energy metabolism and intestinal health by regulating gut microbiota, especially the abundance of SCFAs-producing bacteria Akkermansia and Blautia, thereby exerting therapeutic effects. This provides theoretical support for treatment strategies based on gut microbiota.PMID:40071211 | PMC:PMC11895768 | DOI:10.3389/fmicb.2025.1509548

Front Microbiol. 2025 Feb 25;16:1533851. doi: 10.3389/fmicb.2025.1533851. eCollection 2025.ABSTRACTINTRODUCTION: Straw pellet ration replacing part of silage is of great significance for farmers to save farming costs and solve the lack of feed resources. A comprehensive analysis of rumen microbial and serum metabolite compositions is conducted to promote the development of the modern breeding cows-feeding industry.METHODS: In this study, 18 healthy 2-year-old Simmental breeding cows weighing 550 ± 20 kg were selected and randomly divided into two groups. They were fed under the same feeding conditions for 70 days, of which 8 in the control (CON) group were fed 65% roughage (100% silage) + 35% concentrate, and 10 in the treatment (TRT) group were fed 65% roughage (50% corn stover pellets +50% silage) + 35% concentrate, and milk quality, serum immunity indexes, serum metabolomes, rumen fermentation parameters, rumen Microorganisms.RESULTS: The results showed that there was no significant difference in production performance between the two groups of breeding cows fed hay and Corn stover pellet feed (p < 0.05); Immunoglobulin A (IgA) was significantly higher in TRT compared to CON (p < 0.05), and there was no significant difference in Immunoglobulin G (IgG) and Immunoglobulin M (IgM) between the two groups (p > 0.05); a total of 92 differential metabolites were screened out in the serum metabolomics analysis, among them, L-valine, L-leucine, L-arginine, L-cysteine, L-tyrosine, and L-tryptophan were up-regulated; In rumen fermentation parameters there was no significant difference between CON and TRT in rumen pH, rumen ammonia nitrogen (NH3-N) content, rumen Acetic/Propionic concentration (p > 0.05), and the concentration of Acetic, Propionic, butyric and Total volatile fatty acids (TVFA) in CON was significantly lower than that in TRT (p < 0.05). Among the rumen microorganisms, the dominant groups were Thick-walled Firmicutes, Bacteroidota, Prevotella and Ruminalococcus. In the correlation analysis between rumen fermentation parameters and rumen microorganisms, Propionic and TVFA showed a significant positive correlation with Prevotella (p < 0.05), butyric showed a highly significant positive correlation with Prevotella (p < 0.01), and propionic butyric, and TVFA showed a positive correlation with Bacteroides (p < 0.05); L-cysteine was significantly positively correlated with Prevotella and Anaeroplasma (p < 0.05) and Eubaterium in rumen microbial-serum metabolite correlation analysis (p < 0.01).CONCLUSION: The microbial and metabolomic analyses provide us with essential data support to further provide a scientific basis for breeding cows feeding through the feeding pattern of straw pellets instead of silage, which will help breeding cows farming in future research.PMID:40071207 | PMC:PMC11895767 | DOI:10.3389/fmicb.2025.1533851

Food Chem X. 2025 Feb 19;26:102295. doi: 10.1016/j.fochx.2025.102295. eCollection 2025 Feb.ABSTRACTThe lipid profiles in raw fat (RF) and thermal-extracted fat (TF) from yak under hydroxyl radical-induced oxidative stress were investigated. Both hydroxyl radical and thermal extraction accelerated lipid oxidation. A total of 1168 lipids were identified and classified into 18 lipid categories. The top eight classes of lipids included PCs, PEs, TGs, SMs, CERs, PSs, FAs and PAs. Furtherly, 432 differentially abundant lipids were detected in TF samples compared to RF samples. RF and TF samples displayed a complete distinction in lipidomic profiles, and some lipids in both RF and TF samples demonstrated remarkable differences in abundance with the increasing of H2O2 concentration. RF samples demonstrated a relatively higher abundance of PCs, PEs, PSs, PGs and PIs, while TF samples exhibited a higher level of PAs, TGs, FAs and CERs. These findings indicated that radical attack and thermal extraction severely affected lipid oxidation and lipid metabolomics.PMID:40071140 | PMC:PMC11894325 | DOI:10.1016/j.fochx.2025.102295

Front Immunol. 2025 Feb 25;16:1469737. doi: 10.3389/fimmu.2025.1469737. eCollection 2025.ABSTRACTSterile systemic inflammation may contribute to neuroinflammation and accelerate the progression of neurodegenerative diseases. The double-stranded RNA-dependent protein kinase (PKR) is a key signaling molecule that regulates immune responses by regulating macrophage activation, various inflammatory pathways, and inflammasome formation. This study aims to study the role of PKR in regulating sterile systemic inflammation-triggered neuroinflammation and cognitive dysfunctions. Here, the laparotomy mouse model was used to study neuroimmune responses triggered by sterile systemic inflammation. Our study revealed that genetic deletion of PKR in mice potently attenuated the laparotomy-induced peripheral and neural inflammation and cognitive deficits. Furthermore, intracerebroventricular injection of rAAV-DIO-PKR-K296R to inhibit PKR in cholinergic neurons of ChAT-IRES-Cre-eGFP mice rescued the laparotomy-induced changes in key metabolites of brain glucose metabolism, particularly the changes in phosphoenolpyruvate and succinate levels, and cognitive impairment in short-term and spatial working memory. Our results demonstrated the critical role of PKR in regulating neuroinflammation, brain glucose metabolism and cognitive dysfunctions in a peripheral inflammation model. PKR could be a novel pharmacological target for treating systemic inflammation-induced neuroinflammation and cognitive dysfunctions.PMID:40070845 | PMC:PMC11893411 | DOI:10.3389/fimmu.2025.1469737

Front Plant Sci. 2025 Feb 25;16:1557544. doi: 10.3389/fpls.2025.1557544. eCollection 2025.ABSTRACTThe oil palm (Elaeis guineensis Jacq.) is a perennial oilseed crop whose mesocarp produces palm oil rich in the unsaturated fatty acid oleic acid, known for its oxidative stability and cardiovascular health benefits. However, the regulatory mechanisms and pathways responsible for variations in oleic acid biosynthesis during fruit development remain inadequately elucidated. The study examined the mesocarp of oil palm fruits from three developmental stages in seedless and Tenera varieties to evaluate oleic acid content. Fruits from Seedless (MS) and Tenera (MT) oil palms, pollinated for 95 days (MS1 and MT1), 125 days (MS2 and MT2), and 185 days (MS3 and MT3), were analyzed using metabolomics via liquid chromatography-tandem mass spectrometry (LC-MS/MS). RNA sequencing was conducted to profile gene expression associated to oleic acid biosynthesis and accumulation. Differential genes and metabolites were mapped and functionally enriched through KEGG pathway analysis. The result revealed that SAD, FabD, LACS6, BC, FabB, and FabI were positively associated with oleic acid content, whereas LACS9 exhibited either a negative or strongly negative correlation. By integrating metabolomic and transcriptomic techniques, this study elucidates the distinct mechanisms of oleic acid biosynthesis in seedless and thin-shelled oil palm varieties. These findings provide a scientific foundation for enhancing oleic acid content and improving the quality of oil palm-derived products.PMID:40070716 | PMC:PMC11893603 | DOI:10.3389/fpls.2025.1557544

Front Plant Sci. 2025 Feb 25;16:1529598. doi: 10.3389/fpls.2025.1529598. eCollection 2025.ABSTRACTNicosulfuron can repress the growth and quality of sweet corn (Zea mays), and graphene oxide has been used for sustainable agriculture. However, the underlying mechanism of the toxicity of nicosulfuron that is mediated in sweet corn remains elusive. To explore the potential mechanism of GO-mediated nicosulfuron toxicity in sweet corn in this study, we investigated the effects of graphene oxide on nicosulfuron stress in the sweet corn sister inbred lines of H01 and H20. Furthermore, we performed a metabolomics analysis for the H01 and H20 under different treatments. The results showed that nicosulfuron severely affected the rate of survival, physiological parameters, photosynthetic indicators, and chlorophyll fluorescence parameters of corn seedlings, whereas foliar spraying with graphene oxide promoted the rate of survival under nicosulfuron toxicity. The metabolomics analysis showed that 70 and 90 metabolites differentially accumulated in the H01 and H20 inbred lines under nicosulfuron treatment, respectively. Graphene oxide restored 59 metabolites in the H01 seedlings and 56 metabolites to normal levels in the H20 seedlings, thereby promoting the rate of survival of the sweet corn seedlings. Compared with nicosulfuron treatment alone, graphene oxide resulted in 108 and 66 differential metabolites in the H01 and H20 inbred lines, respectively. A correlation analysis revealed that metabolites, such as doronine and (R)-2-hydroxy-2-hydroxylase-1,4-benzoxazin-3(4-hydroxylase)-1, were significantly correlated with the rate of survival, photosynthetic parameters and chlorophyll fluorescence parameters. Furthermore, metabolites related to the detoxification of graphene oxide were enriched in the flavonoid metabolic pathways. These results collectively indicate that graphene oxide can be used as a regulator of corn growth and provide insights into their use to improve crops in areas that are contaminated with nicosulfuron.PMID:40070713 | PMC:PMC11893866 | DOI:10.3389/fpls.2025.1529598