PubMed

Front Vet Sci. 2024 Dec 18;11:1512081. doi: 10.3389/fvets.2024.1512081. eCollection 2024.ABSTRACTINTRODUCTION: Postpartum dairy cows are susceptible to negative energy balance caused by decreased feed intake and the initiation of lactation. Sijunzi San, a famous Chinese traditional herbal formulation, can promote gastrointestinal digestion and absorption and improve disorders of intestinal microbiota. Therefore, we hypothesized that Sijunzi San might alleviate negative energy balance in postpartum dairy cows by modulating the structure of the rumen microbiota and enhancing its fermentation capacity.METHODS: Liquid chromatography-mass spectrometry (LC-MS/MS) was utilized in vitro to identify the main active ingredients in the Sijunzi San. Techniques including in vitro ruminal fermentation, gas chromatography, and 16S rRNA high-throughput sequencing were employed to evaluate their effects on the structure of the rumen microbiota. To test their in vivo effects, sixteen postpartum Holstein dairy cows, with similar body condition and parity, were randomly assigned to two groups, with 8 cows per group. The CONT group was fed a basic diet, while the SJZS group received an additional 300 g/d of Sijunzi San along with the basic diet, continuously for 7 days. ELISA and untargeted metabolomics using ultra-high-performance liquid chromatography-tandem mass (UHPLC-MS/MS) were employed to assess the impacts on immunoglobulin levels, fat mobilization, and the blood metabolome in postpartum dairy cows.RESULTS: Doses of 100 to 500 mg of the Sijunzi San significantly enhanced gas production, microbial protein (MCP), and short-chain fatty acid (SCFA) levels, while notably reducing pH and NH3-N content (p < 0.05), exhibiting a significant dose-dependent relationship. The results revealed that 500 mg of the prescription significantly increased the abundances of the Succiniclasticum and Prevotella genera and notably decreased the abundances of the Christensenellaceae_R-7_group, Muribaculaceae, UCG-005, Comamonas, and F082 genera (p < 0.05). Succiniclasticum and Prevotella showed a significant positive correlation with ruminal SCFAs, whereas UCG-005 exhibited a significant negative correlation with them (p < 0.05). Additionally, Luteolin and Glycitein were significantly positively correlated with Prevotella, while Licochalcone B and Liquoric acid were significantly negatively correlated with Comamonas (p < 0.05). Subsequently, the prescription significantly increased the concentrations of IgA, IgM, and microsomal triglyceride transfer protein (MTTP) in the blood (p < 0.01), while reducing the levels of ketones (KET) (p < 0.05), non-esterified fatty acids (NEFA), and triglycerides (TG) (p < 0.01). Notable alterations were observed in 21 metabolites in the blood metabolome (p < 0.05). Additionally, metabolic pathways associated with linoleic acid metabolism and steroid hormone biosynthesis were significantly affected.DISCUSSION: The findings suggest that administering Sijunzi San to dairy cows during the postpartum period can ameliorate negative energy balance by stimulating rumen fermentation and modifying the composition and abundance of the rumen microbiota.PMID:39744717 | PMC:PMC11688294 | DOI:10.3389/fvets.2024.1512081

Front Mol Biosci. 2024 Dec 18;11:1426964. doi: 10.3389/fmolb.2024.1426964. eCollection 2024.ABSTRACTBACKGROUND: Breast cancer (BC) is a significant cause of morbidity and mortality in women. Although the important role of metabolism in the molecular pathogenesis of BC is known, there is still a need for robust metabolomic biomarkers and predictive models that will enable the detection and prognosis of BC. This study aims to identify targeted metabolomic biomarker candidates based on explainable artificial intelligence (XAI) for the specific detection of BC.METHODS: Data obtained after targeted metabolomics analyses using plasma samples from BC patients (n = 102) and healthy controls (n = 99) were used. Machine learning (ML) models based on raw data were developed, then feature selection methods were applied, and the results were compared. SHapley Additive exPlanations (SHAP), an XAI method, was used to clinically explain the decisions of the optimal model in BC prediction.RESULTS: The results revealed that variable selection increased the performance of ML models in BC classification, and the optimal model was obtained with the logistic regression (LR) classifier after support vector machine (SVM)-SHAP-based feature selection. SHAP annotations of the LR model revealed that Leucine, isoleucine, L-alloisoleucine, norleucine, and homoserine acids were the most important potential BC diagnostic biomarkers. Combining the identified metabolite markers provided robust BC classification measures with precision, recall, and specificity of 89.50%, 88.38%, and 83.67%, respectively.CONCLUSION: In conclusion, this study adds valuable information to the discovery of BC biomarkers and underscores the potential of targeted metabolomics-based diagnostic advances in the management of BC.PMID:39744676 | PMC:PMC11688212 | DOI:10.3389/fmolb.2024.1426964

Front Plant Sci. 2024 Dec 18;15:1480079. doi: 10.3389/fpls.2024.1480079. eCollection 2024.ABSTRACTSelenium nanoparticles (SeNPs) can be absorbed by plants, thereby affecting plant physiological activity, regulating gene expression, and altering metabolite content. However, the molecular mechanisms by which exogenous selenium affects Polygonatum kingianum coll.et Hemsl plant secondary metabolites remain unclear. In this study, we exposed P. kingianum plants to SeNPs at 0, 10, 25, and 50 mg/L concentrations. Joint physiological, metabolomic, and transcriptomic analyses were performed to reveal the response mechanisms of major secondary metabolites of P. kingianum to SeNPs. Our data shows that under the treatment of 25 mg/L, the photosynthetic electron transfer rate of plants significantly increases and the carbon-nitrogen ratio significantly decreases. In parallel, the main active components, polysaccharides and saponins, showed a significant increase in content, while flavonoid content decreased. SeNPs affect polysaccharide accumulation mainly through up-regulation of SPS, UGPase, AGPase, UTP, and SUS genes in starch and sucrose metabolic pathways. The accumulation of saponins was affected by upregulating genes in the sesquiterpenoid and triterpenoid biosynthesis pathways, including PAD, ADH, PK, and GS. The accumulation of flavonoids was mainly regulated by metabolic pathways such as flavonoid biosynthesis, isoflavonoid biosynthesis, and the biosynthesis of phenylpropanoids. In summary, this study reveals the key metabolic pathways affected by SeNPs in the main secondary metabolic products of P. kingianum.PMID:39744600 | PMC:PMC11688289 | DOI:10.3389/fpls.2024.1480079

J Cancer. 2025 Jan 1;16(1):265-278. doi: 10.7150/jca.102722. eCollection 2025.ABSTRACTLung cancer is one of the most harmful cancers in the world, endangering the lives and health of many people. Although there are various methods to treat lung cancer at present, but lung cancer is asymptomatic in the early stages and has a high recurrence rate after late treatment which make it difficult to cure with conventional treatments. Drug combinations for the treatment of lung cancer have been used in many clinical studies. In this study, we constructed a recurrence model of Non-Small Cell Lung Cancer (NSCLC) lung cancer and used a combination of Ginsenoside H dripping pills (GH) and vinorelbine (NVB) to treat the recurrence of lung cancer. The results showed that the inhibition rate of the combined treatment of GH and NVB is 74.81% which is significantly higher than the therapeutic effect of separate use. We also used GC-TOF/MS-based metabolomics to identify differentially abundant metabolites in relapse models and explore biomarker trends. We found that there are 12 metabolite differences in the abundance of metabolites between the treatment groups (GH group, NVB group and GH-NVB group) and the model group, such as glucose 6-phosphate, palmitoleic acid, linoleic acid, guanine, allantoic acid. The differences in these metabolites involve glucose and lipid metabolism, amino acid metabolism, and purine metabolism. We further analyzed the changes in the content of these metabolites and found that the combined use of GH and NVB can regulate purine metabolism, folate synthesis, and thiamine metabolism, ultimately reducing the abnormal increase in alkaline phosphatase (AP). This study provides a method for the treatment of lung cancer and some biomarkers for the detection of lung cancer.PMID:39744563 | PMC:PMC11660129 | DOI:10.7150/jca.102722

Front Aging Neurosci. 2024 Dec 18;16:1511437. doi: 10.3389/fnagi.2024.1511437. eCollection 2024.ABSTRACTINTRODUCTION: Previous research has suggested a link between the onset of Alzheimer's disease (AD) and metabolic disorder; however, the findings have been inconsistent. To date, the majority of metabolomics studies have focused on AD, resulting in a relative paucity of research on early-stage conditions such as mild cognitive impairment (MCI) underexplored. In this study, we employed a comprehensive platform for the early screening of individuals with MCI using high-throughput targeted metabolomics.METHOD: We included 171 participants including 124 individuals with MCI and 47 healthy subjects. Univariate statistical analysis was conducted using t-tests or Wilcoxon rank-sum tests, with p-values corrected by the Benjamini-Hochberg method. The screening criteria were set at FDR < 0.05 and fold change (FC) > 1.5 or < 0.67. Multivariate analysis was performed using orthogonal partial least squares discriminant analysis (OPLS-DA), where differential metabolites were identified based on variable influence on projection (VIP) scores (VIP > 1 and FDR < 0.05). Random forest analysis was used to further evaluate the ability of the metabolic data to distinguish effectively between the two groups.RESULTS: A total of 14 differential metabolites were identified, leading to the discovery of a biomarker panel consisting of three plasma metabolites including uric acid, pyruvic acid and isolithocholic acid that effectively distinguished MCI patients from healthy subjects.DISCUSSION: These findings have provided a comprehensive metabolic profile, offering valuable insights into the early prediction and understanding of the pathogenic processes underlying MCI. This study holds the potential for advancing early detection and intervention strategies for MCI.PMID:39744523 | PMC:PMC11688483 | DOI:10.3389/fnagi.2024.1511437

J Cancer. 2025 Jan 1;16(2):417-429. doi: 10.7150/jca.102931. eCollection 2025.ABSTRACTPurpose: Thymidylate synthase (TYMS) is a key regulatory enzyme in DNA synthesis. We identified the biological effect and molecular mechanisms of TYMS in colorectal cancer (CRC). Methods: We employed western blot and immunohistochemistry for the assessment of TYMS expression in CRC samples. MTT and colony assay were carried out to illuminate the effect of TYMS on the proliferation of CRC cells. Xenograft models were constructed to evaluate the consequences of TYMS overexpression on CRC in vivo. Metabolomics was utilized to analyze the alterations in cellular molecular metabolites subsequent to TYMS overexpression. The impact of TYMS on NRF2 localization and KEAP1 expression was explored by means of western blot. The expression levels of GSH, ROS, MDA, and PTGS2 mRNA were measured to assess ferroptosis. Results: TYMS expression in CRC tumor tissues was upregulated compared to adjacent non-cancerous tissues. Cells overexpressing TYMS displayed enhanced proliferative capabilities. Metabolomic analysis revealed that overexpression of TYMS was associated with elevated levels of GSH within cells and a decrease in the lipid peroxidation product, 4-hydroxyhexenal. ROS detection assays further demonstrated a significant enhancement in cellular antioxidant capacity due to TYMS overexpression. Overexpression of TYMS downregulated KEAP1 expression and promoted NRF2 translocation into the nucleus. Consequently, transcription of downstream antioxidant genes was upregulated, enhancing cellular antioxidant capacity, reducing ROS levels, diminishing lipid peroxidation products, and heightening resistance to ferroptosis induced by erastin. Additionally, our study indicated that the TYMS inhibitor 5-fluorouracil (5-FU) exhibited favorable drug synergism with erastin. Conclusion: TYMS was overexpressed in CRC, which was correlated with poor prognosis of CRC patients. TYMS enhanced the antioxidant capacity of CRC cells via the KEAP1-NRF2 pathway, thereby increasing resistance to erastin-induced ferroptosis.PMID:39744483 | PMC:PMC11685691 | DOI:10.7150/jca.102931

Int J Biol Sci. 2025 Jan 1;21(1):415-432. doi: 10.7150/ijbs.104311. eCollection 2025.ABSTRACTBackground: Kidney stone disease is a major risk factor for impaired renal function, leading to renal fibrosis and end-stage renal disease. High global prevalence and recurrence rate pose a significant threat to human health and healthcare resources. Investigating the mechanisms of kidney stone-induced injury is crucial. Materials and Methods: We examined the relationship between insulin-like growth factor 1 receptor (IGF1R) and epithelial-mesenchymal transition (EMT) at three levels: in patients with kidney stones, in mice induced with glyoxalate crystals, and in HK2 cells stimulated with calcium oxalate monohydrate (COM). RNA sequencing (RNA-seq) and untargeted metabolomics were used to investigate IGF1R's biological mechanisms, followed by in vivo validation in mice. Results: IGF1R was elevated in the kidney stone model, which was significantly associated with EMT progression. RNA-seq analysis indicated that IGF1R enhances EMT through the JAK2/STAT3 pathway. Further experiments at mRNA and protein levels confirmed the activation of this pathway regulated by IGF1R, promoting EMT. Additionally, untargeted metabolomics revealed that IGF1R drives the activation of lactate dehydrogenase A (LDHA) in glycolysis, further facilitating EMT. In vivo experiments confirmed that IGF1R increases LDHA activity through the activation of the JAK2/STAT3 pathway, thereby enhancing the EMT. Conclusion: IGF1R promotes EMT in COM-induced kidney injury by activating LDHA via the JAK2/STAT3 signaling.PMID:39744436 | PMC:PMC11667822 | DOI:10.7150/ijbs.104311

Front Microbiol. 2024 Dec 18;15:1507561. doi: 10.3389/fmicb.2024.1507561. eCollection 2024.ABSTRACTINTRODUCTION: Urinary tract infections (UTIs) are one of the most prevalent infections in North America and are caused by a diverse range of bacterial species. Although uropathogenesis has been studied extensively in the context of macromolecular interactions, the degree to which metabolism may contribute to infection is unclear. Currently, most of what is known about the metabolic capacity of uropathogens has been derived from genomics, genetic knockout studies or transcriptomic analyses. However, there are currently very little empirical data on the metabolic activity of uropathogens when grown in urine.METHODS: To address this gap, we conducted a systematic survey of the metabolic activities of eight of the most common uropathogenic bacterial species that collectively represent 99% of uncomplicated UTIs.RESULTS: Liquid chromatography-mass spectrometry (LC-MS) analyses of human urine cultures revealed that uropathogens have four distinct metabolic clades. We generalized these clades as serine consumers (Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis), glutamine consumers (Pseudomonas aeruginosa), amino acid abstainers (Enterococcus faecalis and Streptococcus agalactiae), and amino acid minimalists (Staphylococcus aureus and Staphylococcus saprophyticus). These metabolic classifications can be further subdivided on a species-to-species level.DISCUSSION: This survey provides a framework to understanding the metabolic activity of the diverse range of uropathogens and how these species use divergent metabolic strategies to occupy the same niche.PMID:39744398 | PMC:PMC11688363 | DOI:10.3389/fmicb.2024.1507561

mLife. 2024 Dec 24;3(4):573-577. doi: 10.1002/mlf2.12153. eCollection 2024 Dec.ABSTRACTThrough the analysis of data from children aged 6 months to 8 years enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART), significant simultaneous associations were identified between variants in the fragile histidine triad (FHIT) gene, children's body mass index, microbiome features related to obesity, and key lipids and amino acids. These patterns represent evidence of the genotype influence in shaping the host microbiome in developing stages and new potential biomarkers for childhood obesity, insulin resistance, and type 2 diabetes.PMID:39744095 | PMC:PMC11685832 | DOI:10.1002/mlf2.12153

Nat Prod Bioprospect. 2025 Jan 2;15(1):2. doi: 10.1007/s13659-024-00485-5.ABSTRACTAngelica L. has attracted global interest for its traditional medicinal uses and commercial values. However, few studies have focused on the metabolomic differences among the Angelica species. In this study, widely targeted metabolomics based on gas chromatography-tandem mass spectrometry was employed to analyze the metabolomes of four Angelica species (Angelica sinensis (Oliv.) Diels (A. sinensis), Angelica biserrata (R.H.Shan & Yuan) C.Q.Yuan & R.H.Shan (A. biserrata), Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav. (A. dahurica) and Angelica keiskei Koidz. (A. keiskei)). A total of 698 volatile metabolites were identified and classified into fifteen different categories. The metabolomic analysis indicated that 7-hydroxycoumarin and Z-ligustilide accumulated at significantly higher levels in A. sinensis, whereas bornyl acetate showed the opposite pattern. Furthermore, a high correspondence between the dendrogram of metabolite contents and phylogenetic positions of the four species. This study provides a comprehensive biochemical map for the exploitation, application and development of the Angelica species as medicinal plants or health-related dietary supplements.PMID:39743660 | DOI:10.1007/s13659-024-00485-5

Nature. 2025 Jan 1. doi: 10.1038/s41586-024-08335-7. Online ahead of print.ABSTRACTLung metastases occur in up to 54% of patients with metastatic tumours1,2. Contributing factors to this high frequency include the physical properties of the pulmonary system and a less oxidative environment that may favour the survival of cancer cells3. Moreover, secreted factors from primary tumours alter immune cells and the extracellular matrix of the lung, creating a permissive pre-metastatic environment primed for the arriving cancer cells4,5. Nutrients are also primed during pre-metastatic niche formation6. Yet, whether and how nutrients available in organs in which tumours metastasize confer cancer cells with aggressive traits is mostly undefined. Here we found that pulmonary aspartate triggers a cellular signalling cascade in disseminated cancer cells, resulting in a translational programme that boosts aggressiveness of lung metastases. Specifically, we observe that patients and mice with breast cancer have high concentrations of aspartate in their lung interstitial fluid. This extracellular aspartate activates the ionotropic N-methyl-D-aspartate receptor in cancer cells, which promotes CREB-dependent expression of deoxyhypusine hydroxylase (DOHH). DOHH is essential for hypusination, a post-translational modification that is required for the activity of the non-classical translation initiation factor eIF5A. In turn, a translational programme with TGFβ signalling as a central hub promotes collagen synthesis in lung-disseminated breast cancer cells. We detected key proteins of this mechanism in lung metastases from patients with breast cancer. In summary, we found that aspartate, a classical biosynthesis metabolite, functions in the lung environment as an extracellular signalling molecule to promote aggressiveness of metastases.PMID:39743589 | DOI:10.1038/s41586-024-08335-7

Int Dent J. 2024 Dec 31:S0020-6539(24)01620-4. doi: 10.1016/j.identj.2024.12.002. Online ahead of print.ABSTRACTBACKGROUND AND AIM: Recent studies have shown that electronic cigarettes (ECs) use disrupts the oral microbiome composition and diversity, impairing the metabolic pathways of the mucosal cells. However, to date, no reports have evaluated the role of EC exposure in the context of oral metabolome. Hence, the aim of this study was to investigate the role of EC aerosol exposure in the dysregulation of the oral microbiome and metabolome profile using in vitro 3D organotypic models of human oral mucosa.METHODS: 3D tissue-engineered human oral mucosa models were generated and infected with oral microbes obtained from saliva of a healthy donor. The epithelial surface of the oral mucosal models was exposed directly to the EC aerosol (flavoured; with and without nicotine) as it came out of a simulated activated device that mimicked the clinical situation. A comprehensive assessment of oral microbiome community composition by bacterial 16S rRNA gene sequencing was performed. A gas chromatography-based mass spectrometry analysis was also conducted to identify the effect of vaping on the oral metabolome profile.RESULTS: A higher alpha diversity in flavoured EC with nicotine groups was observed compared to controls, with notable differences in bacterial taxa abundance. Metabolomics analysis further demonstrated distinct clustering of control, EC with flavoured nicotine, and flavoured EC groups, confirming 13 metabolites that were statistically higher in levels in flavoured EC with nicotine group, indicating the adverse effects of nicotine on the oral mucosa model. Altered metabolites were mainly enriched in pathways associated with oral cancer progression.CONCLUSION: This study underscores the significant impact of EC use on oral health, highlighting alterations in the oral microbiome, bacterial composition, and metabolite profiles via a clinically relevant in vitro 3D organotypic model of human oral mucosa.PMID:39743449 | DOI:10.1016/j.identj.2024.12.002

Int J Biol Macromol. 2024 Dec 30:139357. doi: 10.1016/j.ijbiomac.2024.139357. Online ahead of print.ABSTRACTLiver cancer was the third cause of global cancer death, while China has the largest number of patients. And traditional Chinese medicine is an important strategy for liver cancer. There into, Huaier polysaccharides (HP), the major component of Trametes robiniophila Murr., as a preparation of Huaier granule, is recommended by clinical guidelines for Hepatocellular carcinoma (HCC). However, the anti-HCC mechanism remains unclear. Herein, we investigated whether HP could suppress HCC and revealed the underlying mechanism. Firstly, HP showed a weaker proliferation inhibitory effect on the mouse source and human HCC cells in vitro, but exhibited stronger anti-HCC effects in animals. And nude mice models confirmed that macrophages play an important role in the anti-HCC effect of HP. Then, we observed that HP reduced the polarization of M2 macrophages in tumor microenvironment and increased the secretion of pro-inflammatory factors by macrophages. Moreover, 16 s rRNA gene sequencing and non-targeted metabolomics analysis revealed that HP altered the gut microbiota and related metabolites. Eventually, antibiotic intervention eliminated the efficacy and reduced the expression of pro-inflammatory factors, confirming that the gut microbiota is a key molecule for HP efficacy. In addition, MTT and EdU assay indicated that Chenodeoxycholic acid (CDCA) were potential microbial metabolites influencing efficacy of HP. In conclusion, our data revealed that Huaier polysaccharides inhibited HCC via gut microbiota mediated M2 macrophage polarization, providing sufficient scientific support for Huaier polysaccharides clinical application and indicating the indispensable role of polysaccharides in life health.PMID:39743053 | DOI:10.1016/j.ijbiomac.2024.139357

Plant Physiol Biochem. 2024 Dec 26;219:109456. doi: 10.1016/j.plaphy.2024.109456. Online ahead of print.ABSTRACTTo improve the selenium (Se) uptake in grapes, the effects of arbuscular mycorrhizal fungi (AMF) on the Se accumulation in grapevines were studied under a soil Se concentration of 5 mg/kg, and the transcriptome and metabolome sequencing were used to elucidate the regulatory mechanism of AMF on Se accumulation. AMF initially decreased the biomass of grapevines, but later increased the biomass. Moreover, AMF enhanced the activities of Se metabolism enzymes (adenosine triphosphate sulfurylase, adenosine 5'-phosphosulfate reductase, serine acetyltransferase, and cysteine methyltransferase) and the Se concentration in grapevines. Compared to Se treatment alone, AMF resulted in a 20% increase in root Se concentration and a 21% increase in shoot Se concentration 60 days after treatment. Transcriptome and metabolome analyses revealed that AMF up-regulated the expression levels of inorganic phosphate transporter proteins 1-11 and down-regulated the expression levels of ABC transporter family members, water channel proteins, and sulfur transporter proteins in grapevines. In addition, AMF elevated the levels of hesperidin, naringenin, apigenin, neohesperidin, pine sapogenin, and rutin in grapevines. Therefore, AMF can enhance Se accumulation in grapes by modulating the phosphate transport pathway and the biosynthesis of secondary metabolites involved in the phenylpropane biosynthesis pathway, flavonoid biosynthesis pathway, and flavonoid and flavonol biosynthesis pathway.PMID:39742784 | DOI:10.1016/j.plaphy.2024.109456

Int Immunopharmacol. 2024 Dec 31;147:113651. doi: 10.1016/j.intimp.2024.113651. Online ahead of print.ABSTRACTSepsis is the leading cause of death among critically ill patients in clinical practice, making it urgent to reduce its incidence and mortality rates. In sepsis, macrophage dysfunction often worsens and complicates the condition. M1 and M2 macrophages, two distinct types, contribute to pro-inflammatory and anti-inflammatory effects, respectively. An imbalance between them is a major cause of sepsis. The aim of this study was to explore the potential of a differential metabolite between M1 and M2 macrophages in mitigating septic colonic injury via multiomics in combination with clinical data and animal experiments. Using nontargeted metabolomics analysis, we found that Kynurenic acid (KYNA), a metabolite of tryptophan metabolism, was significantly upregulated in the supernatant of M2 macrophages. Furthermore, we discovered that the level of KYNA was significantly decreased in sepsis in both human and mouse serum and was negatively correlated with inflammatory factor levels. In vivo experiments demonstrated that KYNA can effectively alleviate septic colon injury and reduce inflammatory factor levels in mice, indicating that KYNA plays a very important protective role in sepsis. Mechanistically, KYNA promotes the transition of M1 macrophages to M2 macrophages by inhibiting the NF-κB signaling pathway and alleviates septic colonic injury through the PPARγ/NF-κB axis. This article reveals that KYNA, a differentially abundant metabolite between M1 and M2 macrophages, can become a new strategy for alleviating septic colon injury.PMID:39742725 | DOI:10.1016/j.intimp.2024.113651

J Pharm Biomed Anal. 2024 Dec 26;255:116651. doi: 10.1016/j.jpba.2024.116651. Online ahead of print.ABSTRACTMyocardial infarction (MI) is a major cause of death worldwide. Exercise rehabilitation (ER) is a powerful tool to improve life quality and prognosis of MI patients. Herein, we developed an untargeted metabolomics combined with lipidomics method to qualitatively and quantitatively detect metabolites in plasma. A total of 475 metabolites were annotated according to MS, MS/MS, and quantified by internal standard method. Moreover, medical statistical methods combined with chemometrics were used for metabolomics data mining and interpretation of clinical issues (matched Cohort 1, n = 90, Cohort 2, n = 6). The results illustrated that abnormal lipid metabolism is the most significant metabolic disorder for MI patients. And, three metabolic pathways, bile secretion, HIF-1 signaling pathway, and glutathione metabolism were uncovered in MI patients. Furthermore, glutamine, Phenylacetylglutamine (PAGln) and lysophosphatidylcholine (LPCs) were revealed as the essential biomarkers for ER of MI patients. Our findings revealed the metabolic landscape of MI and metabolic alterations after ER, will underlay potential applications of plasma metabolites in the detection of MI and optimization of ER program.PMID:39742691 | DOI:10.1016/j.jpba.2024.116651

Ultrason Sonochem. 2024 Dec 30;112:107215. doi: 10.1016/j.ultsonch.2024.107215. Online ahead of print.ABSTRACTApple pectin (AP), a well-established dietary fiber, offers significant health benefits, particularly in immunomodulation. However, the structure-activity relationship (SAR) in this context remains poorly understood. This study aimed to elucidate the impact of varying degrees of esterification (DE) on AP's SAR in immunomodulatory activity. AP-Es (AP-E1, AP-E2, AP-E3) with different DE were prepared using mild ultrasound-assisted alkali de-esterification, followed by SAR analysis. Results revealed that AP-E3, with the lowest DE (5.08 ± 0.22 %), demonstrated a significant reduction in homogalacturonan (HG) domains and a corresponding increase in rhamnogalacturonan-I (RG-I) domains, which coincided with enhanced immunomodulatory effects. The molecular weights of AP-E1, AP-E2, and AP-E3 were determined to be 30.94 ± 0.83 kDa, 27.61 ± 0.65 kDa, and 22.17 ± 0.57 kDa, respectively. To further explore the underlying mechanism, transgenic zebrafish with fluorescent macrophages were utilized. A positive correlation was observed between AP-E3 concentration and the number of fluorescent microspheres engulfed by macrophages. Additionally, AP-E3 significantly upregulated the expression of key immune response genes (tnf-α, il-1β, il-6, cox-2, inos, and nf-κb) and restored the gut microbiota composition and abundance in chloramphenicol-induced immunocompromised zebrafish. Metabolomics analysis revealed that AP-E3 effectively restored metabolic homeostasis by activating multiple signaling pathways associated with signal transduction, immune regulation, and metabolism. These findings highlight the potential of low-esterified AP enriched with RG-I domains as a promising candidate for applications in immune modulation and gut health management.PMID:39742686 | DOI:10.1016/j.ultsonch.2024.107215

Ecotoxicol Environ Saf. 2024 Dec 31;290:117635. doi: 10.1016/j.ecoenv.2024.117635. Online ahead of print.ABSTRACTSaline-alkaline aquaculture plays a crucial role in the ecological restoration of saline soils, yet high water salinity can significantly restrict the growth of cultured organisms. The Chinese mitten crab (Eriocheir sinensis) is typically farmed in freshwater, to evaluate the effects of salinity stress on these crabs, this study conducted laboratory aquaculture experiments at salinities of ≤ 0.5 (freshwater), 6, 12, and 18 ‰. Regular data on crab survival and growth were collected over 35 days. Subsequently, tissues including the eyestalk, posterior gill, hepatopancreas, and ovary were sampled from crabs in both the freshwater control group and the 18 ‰ salinity treatment group for transcriptional and metabolomic analysis. The omics data were used to ascertain the physiological mode of action (pMoA) affected by salinity in the crabs. A dynamic energy budget toxicokinetic-toxicodynamic (DEB-TKTD) model was built based on these pMoAs to predict the life history traits of crabs across different salinities, including survival, growth, and reproduction. The omics results indicated that at 18 ‰, the osmoregulatory capacity and oxidative stress resistance were enhanced, and vitellogenin synthesis was stimulated. This suggests that the two pMoAs involved increasing maintenance costs and reallocating energy between soma and reproduction. DEB-TKTD model predictions fit well with the observed data, with high R2 values (0.9704 for survival, 0.9842 for carapace width, and 0.9283 for reproduction) and low NRMSE (0.0093, 0.1175, and 0.0778, respectively). The predictions indicate that after 60 days, survival rates under salinities of 6, 12, and 18 ‰ decreased by 35.7 %, 56.7 %, and 66.2 %, respectively, compared to freshwater conditions. Growth in carapace width was similarly affected, with reductions of 21.5 %, 42.3 %, and 62.5 %, respectively. The maturation process was accelerated for crabs in saline conditions, with puberty achieved at 45, 36, and 31 days, compared to the freshwater group that had not matured. Furthermore, the LC50 for salinity decreased from 9.07 ‰ (95 % CI: 7.33-10.15 ‰) at 35 days to 4.59 ‰ (95 % CI: 3.12-5.83 ‰) at 60 days. The findings of this study indicate the significant impact of salinity on the survival, growth, and maturation of Chinese mitten crabs by altering maintenance costs and energy allocation. The DEB-TKTD model, informed by omics data, accurately predicts the life history traits of crabs under saline stress. This approach provides an innovative tool for ecological toxicological research in the aquaculture environment.PMID:39742640 | DOI:10.1016/j.ecoenv.2024.117635

Food Chem. 2024 Dec 26;470:142672. doi: 10.1016/j.foodchem.2024.142672. Online ahead of print.ABSTRACTLactic acid bacteria (LAB) fermentation enhances the flavour and functionality of juice substrates; however, research on hawthorn juice is limited. We hypothesize that due to strain specificity, the changes in hawthorn juice after fermentation with different LAB may vary. After selecting LAB strains based on pH and sensory evaluation, the physicochemical properties and anti-inflammatory potential in a lipopolysaccharide-induced RAW 264.7 macrophage model were analysed in vitro. Non-targeted metabolomics revealed fermentation-driven metabolic changes. All strains exhibited increased total acidity and decreased reducing sugar and flavonoid contents. In particular, the Lactobacillus plantarum SC-1.3 and FWDG (strain preservation number) strains suppressed the pro-inflammatory cytokines interleukin-6 and tumour necrosis factor-α, with FWDG exhibiting the strongest effect. Moreover, fermentation resulted in the enrichment of bioactive metabolites, including prunetin and glycitein, which are unique to FWDG. The results provided a basis for the industrialization of hawthorn juice as a dietary product.PMID:39742598 | DOI:10.1016/j.foodchem.2024.142672

Sci Transl Med. 2025 Jan;17(779):eadp5247. doi: 10.1126/scitranslmed.adp5247. Epub 2025 Jan 1.ABSTRACTMutations in lipid regulator genes are a frequent cause of autism spectrum disorder, including those regulating phosphatidylinositol (PI) and phosphoinositide 3-kinase signaling. MBOAT7 encodes a key acyltransferase in PI synthesis and is mutated in an autism-related condition with neurodevelopmental delay and epilepsy. Using liquid chromatography-tandem mass spectrometry, we analyzed the PI-associated glycerolipidome in mice and humans during neurodevelopment and found dynamic regulation at times corresponding to neural apoptosis in the brains of Mboat7 knockout mice. Mboat7 function was necessary for polyunsaturated lipid synthesis and cortical neural migration, and loss resulted in massive accumulation of the precursor lysophosphatidylinositol and hyperactive mTOR signaling. Inhibiting mTOR signaling rescued migration defects. Our findings demonstrate roles for lipid remodeling during neurodevelopment and implicate lipid regulation in neuronal migration, revealing potential paths to treatment for MBOAT7 deficiency.PMID:39742503 | DOI:10.1126/scitranslmed.adp5247