PubMed

Br J Nutr. 2024 Dec 9:1-29. doi: 10.1017/S0007114524002812. Online ahead of print.ABSTRACTPrior observational studies have reported the potential protective effect of omega-3 fatty acids on the prognosis of acute pancreatitis. However, the causal impact of omega-3 fatty acids on acute pancreatitis is unclear. We aimed to investigate further the association of omega-3 fatty acids with acute pancreatitis. We performed a meta-analysis and Mendelian randomization (MR) to explore the association between omega-3 fatty acids and the prognosis of acute pancreatitis from clinical observation and genetics perspectives, respectively. 9 randomized controlled trials were included in this study. The result meta-analysis showed that complementary therapy of omega-3 fatty acids significantly decreased mortality (RR: 0.30; 95% CI 0.14 to 0.65, P＜0.05) and infectious complications in acute pancreatitis (RR: 0.45; 95% CI 0.27 to 0.77, P＜0.05). Compared to the control groups, the hospital stays (MD: -1.02; 95% CI -1.85 to -0.20, P＜0.05) in acute pancreatitis patients with omega-3 fatty acids treatment were statistically reduced. However, the ICU stay (MD: -0.49; 95% CI -1.29 to -0.31, P＞0.05) between control groups and acute pancreatitis patients with omega-3 fatty acids treatment was insignificant. Utilizing genetic susceptibility analysis in the Mendelian randomization (MR) approach, the MR showed omega-3 fatty acids have a significant causal effect on the acute pancreatitis risk (OR, 0.887; 95% CI, 0.797-0.986, P = 0.027, fixed-effect; OR, 0.887; 95% CI, 0.792-0.993, P = 0.037, random-effect). Omega-3 fatty acids complementary therapy may improve the prognosis of acute pancreatitis. Furthermore, genetically predicted serum levels of omega-3 fatty acids can significantly lower acute pancreatitis risk.PMID:39648710 | DOI:10.1017/S0007114524002812

Pharm Biol. 2024 Dec;62(1):341-355. doi: 10.1080/13880209.2024.2318791. Epub 2024 May 9.ABSTRACTCONTEXT: Cervicitis is a common gynecological inflammatory disease. The Chinese herbal prescription Kang-Gong-Yan (KGY) is clinically effective against cervicitis; however, the chemical constituents and therapeutic mechanism of KGY remain elusive.OBJECTIVE: To analyze the chemical constituents of KGY and explore the potential mechanism of KGY in treating cervicitis.MATERIALS AND METHODS: UHPLC-Q-Exactive Plus Orbitrap MS was used to identify the active compounds of KGY; Sprague-Dawley (SD) female rats were randomly divided into the control, model, and KGY groups. Phenol mucilage (25%) was slowly injected into the vagina and cervix of the rats to establish the cervicitis model. Then, rats in the KGY groups (low dose: 1 g/kg/d; medium dose: 5 g/kg/d; high dose: 10 g/kg/d) were continuously gavaged KGY for one week. HE staining was used to observe the cervical tissues of rats; ELISA was used to detect inflammatory factors in plasma; non-targeted metabolomics was used to analyze metabolites; 16S rRNA sequencing was used to analyze intestinal microorganisms.RESULTS: KGY exerted anti-cervicitis effects and decreased the levels of IL-6, IL-1β, and TNF-α. The mechanism of KGY in treating cervicitis is mainly associated with betaine, amino acid, pyrimidine, and phospholipid metabolism by regulating fifteen metabolites. Moreover, KGY reversed cervicitis-induced gut dysbiosis by mediating five bacteria.DISCUSSION AND CONCLUSIONS: The Chinese herbal prescription KGY may alleviate cervicitis by modulating metabolites and gut microbiota disorders. These findings provide a scientific basis for the clinical application of KGY and a new strategy for treating cervicitis in Chinese medicine.PMID:39648685 | DOI:10.1080/13880209.2024.2318791

Prep Biochem Biotechnol. 2024 Dec 8:1-13. doi: 10.1080/10826068.2024.2423665. Online ahead of print.ABSTRACTUsing an engineered Escherichia coli to produce lipase and can easily achieve high-level expression. The investigation of biochemical processes during lipase fermentation, approached from a metabolomics perspective, will yield novel insights into the efficient secretion of recombinant proteins. In this study, the lipase batch fermentation was carried out first with enzyme activity of 36.83 U/mg cells. Then, differential metabolites and metabolic pathways were identified using an untargeted metabolomics approach through comparative analysis of various fermentation periods. In total, 574 metabolites were identified: 545 were up-regulated and 29 were down-regulated, mainly in 153 organic acids and derivatives, 160 organoheterocyclic compounds, 64 lipids and lipid-like molecules, and 58 organic oxygen compounds. Through metabolic pathways and network analysis, it could be found that tryptophan metabolism was of great significance to lipase production, which could affect the secretion and synthesis of recombinant protein. In addition, the promotion effects of cell growth by varying concentrations of indole acetic acid serve to validate the results obtained from tryptophan metabolism. This study offers valuable insights into metabolic regulation of engineered E. coli, indicating that its fermentation bioprocess can be systematically designed according to metabolomics findings to enhance recombinant protein production.PMID:39648316 | DOI:10.1080/10826068.2024.2423665

Vet Comp Oncol. 2024 Dec 8. doi: 10.1111/vco.13034. Online ahead of print.ABSTRACTCanine lymphoma represents a biologically and metabolically heterogeneous group of neoplasms that arise from malignant transformation of lymphoid cells. An accurate diagnosis is crucial because of its impact on survival. Current diagnostic methods include clinical laboratory tests and imaging, most of which are invasive and lack sensitivity and specificity. Interestingly, recent work in cancer patients focuses on the search for biomarkers for diagnosis, investigation of treatment response mechanisms, treatment efficacy and prognosis and the discovery of tumour metabolic pathways using metabolomic analysis. In this study, we compare the metabolite profiles in serum from 37 dogs with multicentric lymphoma (22 B-cell lymphomas/LB, 9 CD45+ T-cell lymphomas/LTCD45+, 6 CD45- T-cell lymphomas/LTCD45-) and 25 healthy dogs using 1H nuclear magnetic resonance spectroscopy (NMR). 1H NMR-based metabolite profiling analysis recognised lipids and 22 metabolites, with 16 of them altered, and was shown to be an effective approach for differentiating samples from dogs with lymphoma and healthy controls based on principal component analysis of the NMR data. We also investigated variations in the serum metabolome between immunophenotypes and the control group through pairwise comparisons of the healthy against the LB, LTCD45+ and LTCD45- groups, respectively which showed similar metabolomic profiles. In addition, there were significant differences in the levels of five individual metabolites based on the univariate statistical analysis. Our results showed alterations in energy, protein and lipid metabolism, suggesting glucose, lactate, N-acetyl glycoproteins (NAGs), scyllo-inositol and choline as possible new candidate biomarkers in canine multicentric lymphoma.PMID:39648045 | DOI:10.1111/vco.13034

Bioresour Technol. 2024 Dec 6:131958. doi: 10.1016/j.biortech.2024.131958. Online ahead of print.ABSTRACTAtmospheric and room temperature plasma mutation and co-mutation with ethanol were employed to generate Haematococcus pluvialis mutants AV3 and AV8. These mutants were screened using multiple indices of chlorophyll fluorescence, quantum yield, lethality, growth rate, dry cell weight, and lipid content. Compared to the wild strain, the mutants demonstrated genetic stability (*p > 0.05) over three cultivation periods, with biomass, lipid content, and growth rate increasing by over 16 %, 55 %, and 45 %, respectively. Lipid accumulation was correlated with higher activities of key lipid biosynthesis enzymes, acetyl-CoA carboxylase, and diacylglycerol acyltransferases. Transcriptomic and metabolomic analyses revealed differentially expressed genes and differential metabolites, with significant changes in glutathione, arginine and Pyruvate metabolism pathways. This study provides new insights into the molecular mechanisms behind enhanced lipid synthesis and highlights the potential of plasma mutation for improving lipid production in microalgae, offering a promising avenue for biofuel production.PMID:39647716 | DOI:10.1016/j.biortech.2024.131958

J Am Acad Dermatol. 2024 Dec 6:S0190-9622(24)03328-0. doi: 10.1016/j.jaad.2024.11.052. Online ahead of print.NO ABSTRACTPMID:39647705 | DOI:10.1016/j.jaad.2024.11.052

J Nutr Biochem. 2024 Dec 6:109830. doi: 10.1016/j.jnutbio.2024.109830. Online ahead of print.ABSTRACTPoor intrauterine environments increase the prevalence for chronic metabolic diseases in offspring, whereas maternal exercise is an effective measure to break this vicious intergenerational cycle. Placenta is increasingly being studied to explore its role in maternal-fetal metabolic cross-talk. The association between placental miRNA and offspring development trajectories has been established, yet the specific role and mechanism thereof in maternal exercise-induced metabolic protection remain elusive. Here, C57BL/6 female mice were subjected to either a normal control or a high-fat diet (HFD), half of the HFD-fed dams were housed with voluntary wheel running for 3 weeks before and during gestation. At embryonic day 18.5, we sacrificed parturient mice and then conducted miRNA-seq, transcriptomic, and metabolomic profiling of the placenta. Our data revealed that maternal HFD resulted in significant alterations in both miRNA and gene expressions, as well as metabolic pathways of the placenta, whereas prenatal exercise negated these perturbations. The common differentially expressed transcripts among three groups were enriched in multiple critical pathways involving energy expenditure, signal transduction, and fetal development. Through integrated analysis of multi-omics data, we speculated that maternal exercise reversed the suppression of miR-495-5p induced by HFD, thereby inhibiting miR-495-5p-targeted Snx7 and modulating kynurenic acid production. These datasets provided novel mechanistic insight into how maternal exercise positively affects the metabolic homeostasis of offspring. The discovered important miRNAs, mRNAs, and metabolites could be promising predictive and therapeutic targets for protecting offspring metabolic health.PMID:39647668 | DOI:10.1016/j.jnutbio.2024.109830

Crit Rev Oncol Hematol. 2024 Dec 6:104590. doi: 10.1016/j.critrevonc.2024.104590. Online ahead of print.ABSTRACTCurrent therapeutic strategies for benign prostatic hyperplasia (BPH) and prostate cancer focus mainly on androgen receptors (AR) and 5-alpha reductase inhibition to suppress androgen-driven prostate growth. However, these methods often result in side effects and resistance. Recent research identifies novel targets like integrin and cadherin inhibitors, gene regulation, microRNAs, cellular senescence, and metabolomics pathways to overcome these limitations. These innovations offer more personalized approaches with potentially fewer adverse effects and reduced resistance compared to traditional androgen-focused therapies. Novel target sites and pathways, either suppressed or overexpressed, offer control points for modulating signaling in prostate diseases, suggesting future potential for treatment through innovative exogenous substances. Data was compiled from Google Scholar, PubMed, and Google to highlight the comparative potential of these emerging methods in enhancing treatment efficacy for prostate health.PMID:39647642 | DOI:10.1016/j.critrevonc.2024.104590

J Adv Res. 2024 Dec 6:S2090-1232(24)00559-9. doi: 10.1016/j.jare.2024.12.003. Online ahead of print.ABSTRACTINTRODUCTION: Cancer-associated fibroblasts (CAFs) are a critical component of the tumor microenvironment, being implicated in enhancing tumor growth and fostering drug resistance. Nonetheless, the mechanisms underlying their function in prostate cancer (PCa) remain incompletely understood, which is essential for devising effective therapeutic strategies.OBJECTIVES: The main objective of this study was to explore the mechanisms by which CAFs mediate PCa growth and chemoresistance.METHODS: We validated through data analysis and experimentation that CAFs significantly impact PCa cell proliferation and chemoresistance. Subsequently, we conducted a comprehensive proteomic analysis of the conditioned media from CAFs and PCa cells and identified angiopoietin-like protein 4 (ANGPTL4) as a key factor. We employed ELISA and multiplex immunofluorescence assays, all of which indicated that ANGPTL4 was primarily secreted by CAFs.Next, we conducted metabolomics analysis, GST pull-down assays, Co-IP, and other experiments to explore the specific molecular mechanisms of ANGPTL4 and its precise effects on PCa cells. Through drug screening, we identified Quercetin 3-O-(6'-galactopyranosyl)-β-D-galactopyranoside (QGGP) as an effective inhibitor of CAFs function. Finally, we thoroughly assessed the therapeutic potential of QGGP both as a monotherapy and in combination with docetaxel in PCa cells RESULTS: We discovered that the extracrine factor ANGPTL4 is primarily expressed in CAFs in PCa. When ANGPTL4 binds to IQ motif-containing GTPase-activating protein 1 (IQGAP1) on the PCa cell membrane, it activates the Raf-MEK-ERK-PGC1α axis, promoting mitochondrial biogenesis and OXPHOS metabolism, and thereby facilitating PCa growth and chemoresistance. Furthermore, virtual and functional screening strategies identified QGGP as a specific inhibitor of IQGAP1 that promotes its degradation. Combined with docetaxel treatment, QGGP can reverse the effects of CAFs and improve the responsiveness of PCa to chemotherapy.CONCLUSIONS: This study uncovers a paracrine mechanism of chemoresistance in PCa and proposes that targeting the stroma could be a therapeutic choice.PMID:39647634 | DOI:10.1016/j.jare.2024.12.003

Phytomedicine. 2024 Nov 29;136:156306. doi: 10.1016/j.phymed.2024.156306. Online ahead of print.ABSTRACTBACKGROUND: Sleep deprivation (SLD) is a widespread condition that disrupts physiological functions and may increase mortality risk. Valeriana officinalis, a traditional medicinal herb known for its sedative and hypnotic properties, contains isobicyclogermacrenal (IG), a newly isolated active compound. However, research on the therapeutic potential of IG for treating SLD remains limited.METHODS: In this study, IG was extracted and characterized from Valeriana officinalis, and an SLD model was established in rats using p-chlorophenylalanine (PCPA). Behavioral tests and pathological studies were conducted to assess the effects of IG on SLD, and transcriptomic and metabolomic analyses were utilized to investigate its underlying mechanisms.RESULTS: IG administration significantly improved the cognitive performance of SLD rats in behavioral tests and ameliorated histological injuries in the hippocampus and cerebral cortex. IG treatment increased the levels of brain-derived neurotrophic factor (BDNF) and neurotransmitters such as serotonin (5-HT) in SLD rats. Additionally, IG directly targets TFRC, thereby improving iron metabolism in the hippocampus. Comprehensive transcriptomic and metabolomic analyses revealed that the improvements from IG stemmed from the mitigation of abnormalities in iron metabolism, cholesterol metabolism, and glutathione metabolism, leading to reduced oxidative stress, ferroptosis, and neuroinflammation in the hippocampus caused by SLD.CONCLUSIONS: Collectively, these findings suggest that IG has the potential to ameliorate neurological damage and cognitive impairment caused by SLD, offering a novel strategy for protection against the adverse effects of SLD.PMID:39647468 | DOI:10.1016/j.phymed.2024.156306

Arch Oral Biol. 2024 Oct 10;171:106107. doi: 10.1016/j.archoralbio.2024.106107. Online ahead of print.ABSTRACTOBJECTIVES: In this study, we explored the efficacy of methanolic extract of Thuja orientalis (TOME) as a novel antibacterial and antibiofilm agent against a cariogenic bacterium, Enterococcus faecalis ATCC 29212.DESIGN: Antibacterial susceptibility studies were conducted and surface morphology analysis was performed using field emission scanning electron microscopy (FESEM). Antibiofilm activity was evaluated through both qualitative and quantitative biofilm inhibition assays and validated by microscopic analysis. In-silico molecular docking studies were conducted using the EDock server. The effectiveness of TOME was substantiated by biofilm model on dentin discs and cytotoxicity towards the HaCaT cell line was assessed using the MTT assay.RESULTS: TOME exhibited significant bactericidal activity with minimum inhibitory concentration of 12.5 mg/mL and additionally, it effectively compromised bacterial cell wall integrity. Qualitative, quantitative and microscopic studies depicted the inhibition of biofilm formation. TOME significantly impacted the production of extracellular polymeric substance and extracellular DNA. Molecular docking studies identified beta-caryophyllene as a potent inhibitor of the Enterococcal surface protein (Esp). Biofilm model depicted the reduction of bacterial load on dentin discs. Additionally, TOME showed reduced cytotoxicity on HaCaT cells, indicating its potential as a safe therapeutic agent.CONCLUSION: These findings highlight TOME's promise for developing novel treatments for dental infections and biofilm-associated diseases. Further research should focus on isolating and characterizing the active compounds within TOME, particularly beta-caryophyllene, to elucidate their precise mechanisms of action.PMID:39647458 | DOI:10.1016/j.archoralbio.2024.106107

J Hazard Mater. 2024 Dec 4;484:136795. doi: 10.1016/j.jhazmat.2024.136795. Online ahead of print.ABSTRACTCadmium (Cd) is easily absorbed by rice and enters the food chain, posing a health risk to humans. Plant growth promoting bacteria (PGPB) can help the plant respond to Cd stress, but the mechanism of PGPB for Cd reduction is unclear. Therefore, this study was conducted and found inoculation with a newly isolated Pseudomonas koreensis promoted the growth of rice and reduced its Cd content. Fluorescent staining using PI and H2O2 probe indicated that PGPB attenuated oxidative damage in rice. Metabolomics revealed that 59 metabolites were upregulated after inoculation, with phenylpropanoids and flavonoids being significantly activated. Spectrophotometry analysis comfirmed the content of flavonoid, lignin, phenol, glutathione, proline and the activities of antioxidant enzymes were higher in the inoculated rice than in the control. Quantitative PCR showed the expression of genes related to phenylpropanoids (OsPAL, OsC4H, Os4CL) and flavonoids (OsCHS, OsCHI) was significantly increased by PGPB, while the genes of heavy metal transporters (OsNRAMP5, OsHMA2, OsIRT1) were significantly decreased. Overall, this study provides an insight into the PGPB-mediated detoxification mechanism in rice under Cd stress and emphasizes the role of phenylpropanoids and flavonoids in the production of low-Cd rice to ensure human health.PMID:39647335 | DOI:10.1016/j.jhazmat.2024.136795

J Pharm Biomed Anal. 2024 Nov 29;255:116587. doi: 10.1016/j.jpba.2024.116587. Online ahead of print.ABSTRACTOxylipins are signaling lipids derived from the oxidation of polyunsaturated fatty acids (PUFAs). In lipidomic studies, human plasma may be subjected to various storage conditions and freeze-thaw cycles, which may impact the analysis of these compounds. In this study, we used liquid chromatography coupled with mass spectrometry (LC-MS) to examine the influence of up to five freeze-thaw cycles (FTCs) on free and total (mostly esterified) oxylipins in human plasma and the influence of temperature and storage duration (4 °C for up to 120 h and -20 °C and -80 °C for 1-98 days) in the presence or absence of butylated hydroxytoluene (BHT) on extracted oxylipins stored in LC-MS amber vials. In fresh plasma subjected to several FTCs, approximately 48 % of the detected free oxylipins were significantly altered by the third cycle, with increases in cytochrome P450 (CYP450) and lipoxygenase (LOX)-derived compounds and reductions in trihydroxylated oxylipins. In contrast, multiple FTCs did not significantly alter esterified oxylipins. At 4 °C, the extracted oxylipins did not change significantly for up to 120 h (5 days). Oxylipin levels remained stable for 98 days at -80 °C but decreased by 98 days at -20 °C. The antioxidant activity of butylated hydroxytoluene (BHT) did not influence oxylipin stability at 4 °C for 120 h or at -80 °C for 98 days, but it reduced oxylipin degradation at -20 °C at 98 days. Conversely, prostaglandin F2α (PGF2α) exhibited substantial increases at -20 °C and -80 °C, independent of BHT. This study demonstrates that (i) unlike free oxylipins, the esterified oxylipin pool remains stable following repeated FTCs, (ii) extracted oxylipins are stable at 4 °C for up to 120 h and at -80 °C for up to 98 days, but not at -20 °C for 98 days, and (iii) BHT may minimize oxylipin degradation of sample extracts stored at -20 °C. This study provides a framework for measuring oxylipins under various freeze-thaw and storage conditions.PMID:39647243 | DOI:10.1016/j.jpba.2024.116587

Sci Total Environ. 2024 Dec 7;958:177929. doi: 10.1016/j.scitotenv.2024.177929. Online ahead of print.ABSTRACTDue to the periodic emission of pollutants, the exposure mode of contaminants in water bodies is mostly pulse exposure, and the toxic effects of fluctuating exposure on aquatic animals are not consistent with traditional toxicological experiments of constant exposure. The toxic effects of heavy metal antimony (Sb) on the swimming behavior of Pelophylax nigromaculatus tadpoles after pulse exposure (PESb) and continuous exposure (CESb) for 28 days were explored. The mechanisms were analyzed from the perspectives of tail muscle metabolism and transcriptomics. Compared to the control group, PESb and CESb decreased the average speed of P. nigromaculatus tadpoles by 25.72 % and 18.08 %, respectively. PESb and CESb led to changes in 70 and 24 metabolites of tail muscle, respectively. PESb led to alterations in metabolic pathways related to pyrimidine metabolism, arginine biosynthesis, and glycerophospholipid metabolism. In contrast, CESb altered metabolic pathways such as alanine, aspartate, and glutamate metabolism. Compared to the control, 1225 and 1139 DEGs were identified for PESb and CESb, respectively. These DEGs were mainly associated with functions such as immune response, DNA replication, protein digestion, and absorption. It can be seen that PESb and CESb can alter the metabolism and transcriptome of the tail muscle of P. nigromaculatus tadpoles, leading to differential expression of individual movements.PMID:39647201 | DOI:10.1016/j.scitotenv.2024.177929

Biochimie. 2024 Dec 5:S0300-9084(24)00293-1. doi: 10.1016/j.biochi.2024.11.015. Online ahead of print.ABSTRACTMicroalgae are active producers of various compounds, including toxic substances. However, their metabolism is very diverse and insufficiently known. We demonstrate an approach that includes growing a new strain of cyanobacterium Leptolyngbya sp. (IPPAS B-1204) on an isotopically labeled medium (D2O) and evaluating the metabolomic composition of these microorganisms after deuterium uptake. Despite the low resolution of the GC-MS method, the interpretation of the obtained spectra allowed us to find out not only the amount of the embedded isotope label but also to assume the position in the structure where the label is embedded. We present the results of reliably detecting more than 30 compounds with isotope labels belonging to various classes of biological compounds produced by this cyanobacterium, revealing the metabolic pathways of entry of this label. We also demonstrate that the synthesis of unsaturated fatty acids is suppressed under the growth on D2O medium. In addition, we found an isotopic effect in the chromatographic separation of isotopically labeled compounds in gas chromatography. These data can be used in the future both for the identification of compounds and the analysis of the biosynthesis pathways of secondary biologically active compounds and in the analysis of the production of isotopically labeled standards of compounds.PMID:39645069 | DOI:10.1016/j.biochi.2024.11.015

Comp Biochem Physiol Part D Genomics Proteomics. 2024 Nov 28;54:101371. doi: 10.1016/j.cbd.2024.101371. Online ahead of print.ABSTRACTWater temperature plays a vital role in shaping the physical conditions crucial for the growth, development and reproduction of fish species. Since limited comprehensive multi-omics analyses exploring the molecular mechanisms of temperature influences on the early life stages of fish. Here, the effects of temperature variations on the growth of Takifugu rubripes, a commercial teleost farmed in Asia were investigated. Nineteen-days-old fugu larvae were subjected to different temperature (15 °C-T15, 20 °C-T20, 25 °C-T25) for 30 days. Liver tissues were harvested at the end of the study for transcriptomic and metabolomic assessments. The T. rubripes larvae in the T15 group showed a significant decrease in total length and body weight compared to the T20 and T25 groups (p < 0.05). 1344, 416, and 2080 differentially expressed genes (DEGs) were identified in T15-vs-T20, T20-vs-T25, and T15-vs-T25 comparisons, respectively. Those DEGs were mainly enriched in metabolic, protein digestion and absorption, steroid biosynthesis, and glycerophospholipid metabolism pathways. 15 DEGs were randomly selected for RNA-seq validation, and the transcriptome results were consistent with the qPCR validation results, illustrating the accuracy of transcriptome sequencing. 340, 238, and 330 significantly different metabolites (SDMs) were identified in positive modes when comparing in T15-vs-T20, T20-vs-T25, and T15-vs-T25, respectively. Additionally, 145, 137, and 159 SDMs were identified in negative modes within the three comparisons. Those SDMs enriched in biosynthesis of secondary metabolites, glycerophospholipid metabolism, linoleic acid metabolism, and metabolic pathways. The integration of transcriptomic and metabolomic analyses indicated that DEGs and SDMs mainly enriched in metabolic pathways. These discoveries provide valuable insights into the effects of temperature on fish larvae in aquaculture, laying a foundation for future breeding approaches aimed at improving the growth of T. rubripes.PMID:39644865 | DOI:10.1016/j.cbd.2024.101371

J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Dec 2;1251:124373. doi: 10.1016/j.jchromb.2024.124373. Online ahead of print.ABSTRACTBACKGROUND: Xuemaitong Capsule (XMT) is a widely recognized traditional Miao medicine extensively utilized in Chinese clinical settings. Previous studies have demonstrated XMT protective effects against acute myocardial ischemia (AMI). However, the mechanism by which XMT provides protection to AMI rats is yet to be fully understood.AIM OF THE STUDY: The purpose of this study was to investigate the protective mechanism of XMT on AMI rats through network pharmacology, traditional pharmacodynamics and metabolomics.MATERIAL AND METHODS: The components and potential targets of XMT were identified through the application of traditional Chinese medicine system pharmacology and traditional Chinese medicine molecular mechanism bioinformatics analysis tools. We constructed herb-composition-target networks and analyzed protein-protein interaction (PPI) networks. The potential mechanism was explored by pathway enrichment analysis. Subsequently, the AMI model was constructed by ligation of the anterior descending branch of the left coronary artery, and XMT protective effects on AMI rats were evaluated by analyzing the myocardial enzyme profiles, electrocardiograms(ECG), Triphenyltetrazolium chloride(TTC) staining, and Hematoxylin-Eosin (HE) staining in AMI rats. Metabolomics based on UHPLC-Q-Exactive Orbitrap MS was used to observe the protective effect of XMT on the serum metabolic profile of AMI, and multivariate statistical analysis further revealed the differential patterns of metabolites after XMT treatment. Finally, integrated pathway analysis was carried out to reveal the biological metabolic mechanism.RESULTS: A total of 392 active components of XMT acted with 624 targets for treating AMI. Pathway enrichment analysis revealed that XMT could treat AMI through TNF, MAPK and PI3K-Akt signaling pathways. Further, XMT could effectively prevent ST-segment elevation in the ECG, reduce the size of myocardial infarction, decrease cardiac weight index and cardiac enzyme levels, and mitigate histological damage in the hearts of AMI rats. In addition, XMT callback 117 metabolites and four metabolic pathways, including taurine and hypotaurine metabolism, phenylalanine metabolism, pyrimidine metabolism and retinol metabolism. Through integrating network pharmacology and metabolomics, we explored the biological mechanism by which XMT treats AMI. It was speculated that the mechanism of XMT is to regulate TNF signaling, PI3K-Akt pathway and MAPK signaling pathway, and participate in cell apoptosis, oxidative stress, immune and inflammatory reaction and other biological processes.CONCLUSION: XMT plays a protective role in AMI rats by regulating multiple metabolic biomarkers, multiple targets and pathways. Therefore, XMT may provide a potential strategy for the treatment of AMI.PMID:39644825 | DOI:10.1016/j.jchromb.2024.124373

EBioMedicine. 2024 Dec 6;111:105482. doi: 10.1016/j.ebiom.2024.105482. Online ahead of print.ABSTRACTBACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with impaired regenerative capacity and poor postoperative prognosis following hepatectomy. Previous research has highlighted the importance of the gut-liver axis in the physiological and pathological processes of the liver. However, the contribution of gut bacteria to the regeneration of livers with MAFLD and its metabolic regulatory mechanisms remain elusive.METHODS: Partial hepatectomy (PHx) was performed on C57Bl/6J mice fed with high-fat diet (HFD) for 12 weeks. Pathological examination, immunohistochemistry, and qRT-PCR analysis were performed to assess the severity of steatosis and proliferative potential. The gut microbiome was examined by 16S rRNA gene sequencing and shotgun metagenomics, whereas liver metabolomics was analysed via untargeted and targeted metabolomics using liquid chromatography-tandem mass spectrometry (LC-MS).FINDINGS: HFD-induced hepatic steatosis in mice led to impaired liver regeneration following PHx. The gut microbiota and liver metabolites were altered along with the liver regeneration process. Longitudinal time-series analysis revealed dynamic alterations in these data, whereas correlation analysis screened out bacterial candidates that potentially influence liver regeneration in MAFLD by modulating metabolic pathways. Among these bacteria, the dominant bacterium Akkermansia was selected for subsequent investigation. MAFLD mice gavaged with Akkermansia muciniphila (A. muciniphila) exhibited reduced liver lipid accumulation and accelerated liver regeneration, possibly through the regulation of the tricarboxylic acid (TCA) cycle.INTERPRETATION: These data demonstrated the interplay between the gut microbiome, liver metabolomics, and liver regeneration in mice with MAFLD. A. muciniphila has the potential to serve as a clinical intervention agent to accelerate postoperative recovery in MAFLD.FUNDING: This work was supported by the Research Project of Jinan Microecological Biomedicine Shandong Laboratory [JNL-2022008B]; the Zhejiang Provincial Natural Science Foundation of China [LZ21H180001]; the Fundamental Research Funds for the Central Universities [No. 2022ZFJH003].PMID:39644773 | DOI:10.1016/j.ebiom.2024.105482

EBioMedicine. 2024 Dec 6;111:105484. doi: 10.1016/j.ebiom.2024.105484. Online ahead of print.ABSTRACTBACKGROUND: Sudden Infant Death Syndrome (SIDS) is a leading cause of postneonatal mortality. The absence of specific biomarkers of SIDS diagnosis and risk leaves a significant gap in understanding SIDS pathophysiology. Metabolomics offers an avenue to better understand SIDS biology and identifying potential biomarkers.METHODS: Using Metabolon Inc., global discovery panel, we analysed 828 metabolites from post-mortem serum samples of infants from the Chicago Infant Mortality Study (CIMS) and the NIH NeuroBioBank (NBB). In total, 300 infants (195 SIDS; 105 non-SIDS) across multiple race/ethnicities (70% Black, 13% White, and 16% Hispanic) were included. Metabolite associations with SIDS were performed using Welch's t-tests, linear and logistic regression, and network-cluster analyses.FINDINGS: We identified thirty-five significant metabolite predictors of SIDS after adjustment for age, sex, race and ethnicity, and post-mortem interval, including ornithine (OR 21.98; p-value 6.44e-7), 5-hydroxylysine (OR 19.48; p-value 6.78e-7), 1-stearoyl-2-linoleoyl-GPC (18:0/18:2) (OR 16.80; p-value 3.4e-7), ribitol (OR 8.19; p-value 4.2e-8), and arabitol/xylitol. Using Weighted Gene Co-expression Network Analysis (WGCNA), ten metabolite clusters were identified. Four exhibited significant associations with SIDS. The two most correlated clusters were enriched for metabolites in the tyrosine metabolism pathway and lipid (sphingomyelins) pathways.INTERPRETATION: We identified metabolite biomarkers within key biological pathways and processes (e.g., nitrogen metabolism, lipid and fatty acid metabolism, stress response, nerve cell communication, hormone regulation, oxidative stress) with potential implications in SIDS pathology. Further research is needed to validate these biomarkers in additional SIDS cohorts.FUNDING: The Chicago Infant Mortality Study was funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute on Deafness and Other Communication Disorders under contract number NO1-HD-3-3188, the Centers for Disease Control and Prevention and the Association of Teachers of Preventive Medicine under cooperative agreement number U50/CCU300860-06, and the Playmates in Heaven Foundation. The current analyses were funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development under 5R01HD101518-04.PMID:39644771 | DOI:10.1016/j.ebiom.2024.105484

J Chromatogr A. 2024 Dec 3;1740:465580. doi: 10.1016/j.chroma.2024.465580. Online ahead of print.ABSTRACTMetabolomics based on hydrophilic interaction liquid chromatography (HILIC) coupled with mass spectrometry (MS) is a powerful tool for polar metabolite identification and quantification to further contribute to biomarker discovery and disease mechanism elucidation. However, matrix effect (ME), which may lead to altered ionization efficiency due to co-eluting compounds, is a significant challenge during biological analysis. Therefore, ME evaluation plays a crucial role during method development. Two approaches to evaluate ME are using stable isotope labelled-internal standards (SIL-IS) and post-column infusion (PCI) of standards. In this study, we developed an untargeted HILIC-MS method by applying four PCI standards for ME evaluation. We found PCI is a compelling approach for ME assessment compared to SIL-IS method due to its advantage in untargeted analysis. Through the ME evaluation and chromatographic performance comparison of 18 SIL standards across three columns and three different mobile phase pH conditions, our findings revealed that the BEH-Z-HILIC column operated at pH 4 with 10 mM ammonium formate exhibited minimal ME and superior performance. The method showed exceptional linearity (R² > 0.98), reliable repeatability (RSD < 15 %), good inter-day precision (RSD < 30 %), and acceptable recovery (>75 %) for all SIL standards. Absolute matrix effect (AME) and relative matrix effect (RME) assessment in three plasma donors revealed a high consistency between PCI and SIL-IS approaches. Finally, this method coupled with the PCI approach was applied to 40 plasma samples. Fifty endogenous compounds were detected and their AME and RME were evaluated. Results showed that many compounds experienced severe ion suppression, though their ME variation between 40 samples is low. In conclusion, PCI method is a robust alternative for monitoring ME and evaluating ME of endogenous compounds during untargeted method optimization and biological analysis.PMID:39644743 | DOI:10.1016/j.chroma.2024.465580