PubMed

Phytomedicine. 2024 Aug 6;133:155919. doi: 10.1016/j.phymed.2024.155919. Online ahead of print.ABSTRACTBACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major clinical and global public health issue, with no specific pharmacological treatment available. Currently, there is a lack of approved drugs for the clinical treatment of NAFLD. Large-leaf yellow tea polysaccharides (YTP) is a natural biomacromolecule with excellent prebiotic properties and significant therapeutic effects on multiple metabolic diseases. However, the specific mechanisms by which YTP regulates NAFLD remain unclear.PURPOSE: This study aims to explore the prebiotic effects of YTP and the potential mechanisms by which it inhibits hepatic cholesterol accumulation in NAFLD mice.METHODS: The effects of YTP on lipid accumulation were evaluated in NAFLD mice through obesity trait analysis and bile acids (BAs) metabolism assessment. Additionally, fecal microbiota transplantation (FMT) was performed, and high-throughput sequencing was employed to investigate the mechanisms underlying YTP's regulatory effects on gut microbiota and BA metabolism.RESULTS: Our study demonstrated that YTP altered the constitution of colonic BA, particularly increasing the levels of conjugated BA and non-12OH BA, which suppressed ileum FXR receptors and hepatic BA reabsorption, facilitated BA synthesis, and fecal BA excretion. The modifications were characterized by a decrease in the levels of FXR, FGF15, FGFR4, and ASBT proteins, and an increase in the levels of Cyp7a1 and Cyp27a1 proteins. YTP might affect enterohepatic circulation and by the activated the hepatic FXR-SHP pathway. Meanwhile, YTP reshaped the intestinal microbiome structure by decreasing BSH-producing genera and increasing taurine metabolism genera. The correlation analysis implied that Muribaculaceae, Pseudomonas, acterium_coprostanoligenes_group, Clostridiales, Lachnospiraceae_NK4A136_group, Delftia, Dubosiella, and Romboutsia were strongly correlated with specific BA monomers.CONCLUSIONS: YTP modulates bile salt hydrolase-related microbial genera to activate alternative bile acid synthesis pathways, thereby inhibiting NAFLD progression. These results suggest that YTP may serve as a potential probiotic formulation, offering a feasible dietary intervention for NAFLD.PMID:39153277 | DOI:10.1016/j.phymed.2024.155919

Obes Surg. 2024 Aug 17. doi: 10.1007/s11695-024-07309-y. Online ahead of print.ABSTRACTAIMS/HYPOTHESIS: Post-bariatric hypoglycemia (PBH) is caused by postprandial hyperinsulinemia, due to anatomical alterations and changes in post-prandial metabolism after bariatric surgery. The mechanisms underlying the failing regulatory and compensatory systems are unclear. In this study, we investigated the differences in post-prandial hormones and metabolic profiles between patients with and without PBH.METHODS: We performed a mixed meal test (MMT) in 63 subjects before and 1 year after Roux-en-Y gastric bypass (RYGB) surgery. Blood was withdrawn at 0, 10, 20, 30, 60, and 120 min after ingestion of a standardized meal. Glucose, insulin, GLP-1, FGF-19, and FGF-21 were measured and untargeted metabolomics analysis was performed on blood plasma to analyze which hormonal and metabolic systems were altered between patients with and without PBH.RESULTS: Out of 63, a total of 21 subjects (33%) subjects developed PBH (glucose < 3.1 mmol/L) after surgery. Decreased glucose and increased insulin excursions during MMT were seen in PBH (p < 0.05). GLP-1, FGF-19, and FGF-21 were elevated after surgery (p < 0.001), but did not differ between PBH and non-PBH groups. We identified 20 metabolites possibly involved in carbohydrate metabolism which differed between the two groups, including increased carnitine and acylcholines in PBH.CONCLUSION: Overall, 33% of the subjects developed PBH 1 year after RYGB surgery. While GLP-1, FGF-19, and FGF-21 were similar in PBH and non-PBH patients, metabolomics analysis revealed changes in carnitine and acyclcholines that are possibly involved in energy metabolism, which may play a role in the occurrence of PBH.PMID:39153140 | DOI:10.1007/s11695-024-07309-y

J Bone Miner Metab. 2024 Aug 17. doi: 10.1007/s00774-024-01545-z. Online ahead of print.ABSTRACTLNTRODUCTION: Postmenopausal osteoporosis (PMOP) can cause postmenopausal women to experience pain and interference. Identifying and exploring potential early diagnostic biomarkers of PMOP is of substantial clinical value and social significance. This study aimed to screen for potential novel diagnostic biomarkers of PMOP through a multiomics approach, providing new directions and ideas for the early prevention and treatment of this disease.MATERIALS AND METHODS: Fifteen postmenopausal women with osteoporosis and 12 without were recruited. Clinical information was collected, and various clinical biochemical parameters were tested. Plasma and fecal samples were collected and analyzed using Olink proteomics and gut microbial metabolomics.RESULTS: The functions of the differentially abundant metabolites were mainly related to autophagy and arginine and proline metabolism and were involved in immunoinflammatory metabolic processes. Olink showed significant differences in the expression of seven inflammation-related proteins between the two groups.CONCLUSION: We demonstrated that metabolic differences between PMOP patients and healthy controls were associated with inflammatory responses and found seven proteins with significant differences. Among these proteins, CDCP1, IL10, and IL-1alpha combined with clinical indicators had high discriminant efficiency in identifying PMOP. This is also the first study to demonstrate noteworthy changes in CDCP1 levels in patients with PMOP.PMID:39153113 | DOI:10.1007/s00774-024-01545-z

Clin Oral Investig. 2024 Aug 17;28(9):489. doi: 10.1007/s00784-024-05883-0.ABSTRACTOBJECTIVE: The present study aimed to determine the salivary flow and metabolomic profile of stimulated and unstimulated saliva in children.MATERIALS AND METHODS: Children who attended the Pediatric Dentistry Clinic of the State University of Rio de Janeiro -UERJ between 3 and 12 years of age were selected. Unstimulated and stimulated whole saliva, using mechanical stimulus, were collected. The samples were centrifuged at 12,000 g, 4oC for 1 h. The 1H- NMR spectra were acquired in 500 MHz equipment. The data were extracted into 0.03 ppm buckets in AMIX, and multivariate analysis (PLS-DA and O-PLS-DA) was performed in Metaboanalyst 2.0. For other analyses, such as salivary flow, the data was tabulated in the SPSS 20.0 statistical package, analyzed descriptively, and after applying the Wilcoxon test. The interval of confidence was set at 95%.RESULTS: The mean age was 7.5 (± 1.94), and 47.0% (n = 31) were female, 63.6% (n = 42). The median flow rate for stimulated saliva was 0.74 (IC 0.10-2.40) and was statistically higher (p < 0.001; Wilcoxon test) than unstimulated was 0.39 (IC 0.00-1.80). Children older than seven years old also presented a higher difference between unstimulated and stimulated saliva (p = 0.003; Mann-Whitney test). The PLS-DA and O-PLS-DA demonstrated a different profile in stimulated and unstimulated saliva. Acetate, glucose, propionate, and lysine were higher in the unstimulated whole saliva than in stimulated saliva. Isoleucine, N-acetyl sugar, hydroxybutyrate, glutamate, leucine, propionate, butyrate, valine, isoleucine, succinate, saturated fatty acid, and histidine were found in greater amounts in the saliva of patients with stimulated saliva.CONCLUSION: The stimulated saliva presented a higher flow rate, and older children exhibited a higher flow rate resulting from it's the stimulus. The mechanical stimulus increased the levels of the major metabolites.PMID:39153029 | DOI:10.1007/s00784-024-05883-0

Eur J Drug Metab Pharmacokinet. 2024 Aug 17. doi: 10.1007/s13318-024-00910-7. Online ahead of print.ABSTRACTDue to interindividual variability in drug metabolism and pharmacokinetics, traditional isoniazid fixed-dose regimens may lead to suboptimal or toxic isoniazid concentrations in the plasma of patients with tuberculosis, contributing to adverse drug reactions, therapeutic failure, or the development of drug resistance. Achieving precision therapy for isoniazid requires a multifaceted approach that could integrate various clinical and genomic factors to tailor the isoniazid dose to individual patient characteristics. This includes leveraging molecular diagnostics to perform the comprehensive profiling of host pharmacogenomics to determine how it affects isoniazid metabolism, such as its metabolism by N-acetyltransferase 2 (NAT2), and studying drug-resistant mutations in the Mycobacterium tuberculosis genome for enabling targeted therapy selection. Several other molecular signatures identified from the host pharmacogenomics as well as other omics-based approaches such as gut microbiome, epigenomic, proteomic, metabolomic, and lipidomic approaches have provided mechanistic explanations for isoniazid pharmacokinetic variability and/or adverse drug reactions and thereby may facilitate precision therapy of isoniazid, though further validations in larger and diverse populations with tuberculosis are required for clinical applications. Therapeutic drug monitoring and population pharmacokinetic approaches allow for the adjustment of isoniazid dosages based on patient-specific pharmacokinetic profiles, optimizing drug exposure while minimizing toxicity and the risk of resistance. Current evidence has shown that with the integration of the host pharmacogenomics-particularly NAT2 and Mycobacterium tuberculosis genomics data along with isoniazid pharmacokinetic concentrations in the blood and patient factors such as anthropometric measurements, comorbidities, and type and timing of food administered-precision therapy approaches in isoniazid therapy can be tailored to the specific characteristics of both the host and the pathogen for improving tuberculosis treatment outcomes.PMID:39153028 | DOI:10.1007/s13318-024-00910-7

Helicobacter. 2024 Jul-Aug;29(4):e13130. doi: 10.1111/hel.13130.ABSTRACTEmerging evidence suggests differential antagonism of lactic acid-producing bacteria (LAB) to Helicobacter pylori, posing challenges to human health and food safety due to unclear mechanisms. This study assessed 21 LAB strains from various sources on H. pylori growth, urease activity, and coaggregation. Composite scoring revealed that Latilactobacillus sakei LZ217, derived from fresh milk, demonstrates strong inhibitory effects on both H. pylori growth and urease activity. L. sakei LZ217 significantly reduced H. pylori adherence of gastric cells in vitro, with inhibition ratios of 47.62%. Furthermore, in vivo results showed that L. sakei LZ217 alleviated H. pylori-induced gastric mucosa damage and inflammation in mice. Metabolomic exploration revealed metabolic perturbations in H. pylori induced by L. sakei LZ217, including reduced amino acid levels (e.g., isoleucine, leucine, glutamate, aspartate, and phenylalanine) and impaired carbohydrate and nucleotide synthesis, contributing to the suppression of ureA (28.30%), ureE (84.88%), and ureF (59.59%) expressions in H. pylori. This study underscores the efficacy of LAB against H. pylori and highlights metabolic pathways as promising targets for future interventions against H. pylori growth and colonization.PMID:39152663 | DOI:10.1111/hel.13130

Eur J Med Res. 2024 Aug 17;29(1):423. doi: 10.1186/s40001-024-02016-x.ABSTRACTBACKGROUND: Salidroside (SAL), derived from Rhodiola, shows protective effects in pulmonary arterial hypertension (PAH) models, but its mechanisms are not fully elucidated.OBJECTIVES: Investigate the therapeutic effects and the mechanism of SAL on PAH.METHODS: Monocrotaline was used to establish a PAH rat model. SAL's impact on oxidative stress and inflammatory responses in lung tissues was analyzed using immunohistochemistry, ELISA, and Western blot. Untargeted metabolomics explored SAL's metabolic regulatory mechanisms.RESULTS: SAL significantly reduced mean pulmonary artery pressure, right ventricular hypertrophy, collagen deposition, and fibrosis in the PAH rats. It enhanced antioxidant enzyme levels, reduced inflammatory cytokines, and improved NO bioavailability by upregulating endothelial nitric oxide synthase (eNOS), soluble guanylate cyclase (sGC), cyclic guanosine monophosphate (cGMP), and protein kinase G (PKG) and decreases the expression of endothelin-1 (ET-1). Metabolomics indicated SAL restored metabolic balance in PAH rats, particularly in arginine metabolism.CONCLUSIONS: SAL alleviates PAH by modulating arginine metabolism, enhancing NO synthesis, and improving pulmonary vascular remodeling.PMID:39152472 | DOI:10.1186/s40001-024-02016-x

Commun Biol. 2024 Aug 16;7(1):1004. doi: 10.1038/s42003-024-06701-9.ABSTRACTChrysosplenium sinicum, a traditional Tibetan medicinal plant, can successfully thrive in low-light environments for long periods of time. To investigate the adaptive evolution of shade plants in low-light environments, we generated a chromosome-scale genome assembly (~320 Mb) for C. sinicum by combining PacBio sequencing and Hi-C technologies. Based on our results, gene families related to photosynthesis and cell respiration greatly expanded and evolved in C. sinicum genome due to intracellular DNA transfer from organelle genome to nuclear genome. Under positive selective pressure, adaptive evolution of light-harvesting complex II (LHCII) component protein CsLhcb1s resulted in the expansion of threonine residues at the phosphorylation site of STN7 kinase, potentially establishing a crucial genomic foundation for enhancing C. sinicum's adaptability in low-light environments. Through transcriptome and metabolome analysis, we identified chrysosplenol and chrysosplenoside as predominant flavonoid metabolites of C. sinicum and predicted their synthesis pathways. In addition, analysis of alternative splicing (AS) revealed that AS events help regulate state transition and flavonoid biosynthesis. The present study provides new insights into the genomes of shade plants exposed to low-light conditions and adaptive evolution of these genomes; in addition, the results improve our current knowledge on the biosynthetic and regulatory processes of chrysosplenol and chrysosplenoside.PMID:39152309 | DOI:10.1038/s42003-024-06701-9

Commun Biol. 2024 Aug 17;7(1):1006. doi: 10.1038/s42003-024-06727-z.ABSTRACTAntibiotic-induced dysbiosis in the fish gut causes significant adverse effects. We use fecal microbiota transplantation (FMT) to accelerate the restoration of florfenicol-perturbed intestinal microbiota in koi carp, identifying key bacterial populations and metabolites involved in the recovery process through microbiome and metabolome analyses. We demonstrate that florfenicol disrupts intestinal microbiota, reducing beneficial genera such as Lactobacillus, Bifidobacterium, Bacteroides, Romboutsia, and Faecalibacterium, and causing mucosal injuries. Key metabolites, including aromatic amino acids and glutathione-related compounds, are diminished. We show that FMT effectively restores microbial populations, repairs intestinal damage, and normalizes critical metabolites, while natural recovery is less effective. Spearman correlation analyses reveal strong associations between the identified bacterial genera and the levels of aromatic amino acids and glutathione-related metabolites. This study underscores the potential of FMT to counteract antibiotic-induced dysbiosis and maintain fish intestinal health. The restored microbiota and normalized metabolites provide a basis for developing personalized probiotic therapies for fish.PMID:39152200 | DOI:10.1038/s42003-024-06727-z

Sci Rep. 2024 Aug 16;14(1):19034. doi: 10.1038/s41598-024-69879-2.ABSTRACTThe development of coronary artery disease (CAD) is significantly affected by impaired endocrine and metabolic status. Under this circumstance, improved prevention and treatment of CAD may result from knowing the connection between metabolites and CAD. This study aims to delve into the causal relationship between human metabolic biomarkers and CAD by using two-sample Mendelian randomization (MR). Utilizing two-sample bidirectional MR analysis, we assessed the correlation between 1400 blood metabolites and CAD, and the metabolites data from the CLSA, encompassing 8299 participants. Metabolite analysis identified 1091 plasma metabolites and 309 ratios as instrumental variables. To evaluate the causal link between metabolites and CAD, we analyzed three datasets: ebi-a-GCST005195 (547,261 European & East Asian samples), bbj-a-159 (29,319 East Asian CAD cases & 183,134 East Asian controls), and ebi-a-GCST005194 (296,525 European & East Asian samples). To estimate causal links, we utilized the IVW method. To conduct sensitivity analysis, we used MR-Egger, Weighted Median, and MR-PRESSO. Additionally, we employed MR-Egger interception and Cochran's Q statistic to assess potential heterogeneity and pleiotropy. What's more, replication and reverse analyses were performed to verify the reliability of the results and the causal order between metabolites and disease. Furthermore, we conducted a pathway analysis to identify potential metabolic pathways. 59 blood metabolites and 27 metabolite ratios nominally associated with CAD (P < 0.05) were identified by IVW analysis method. A total of four known blood metabolites, namely beta-hydroxyisovaleroylcarnitine (OR 1.06, 95% CI 1.027-1.094, FDR 0.07), 1-palmitoyl-2-arachidonoyl (OR 1.07, 95% CI 1.029-1.110, FDR 0.09), 1-stearoyl-2- docosahexaenoyl (OR 1.07, 95% CI 1.034-1.113, FDR 0.07) and Linoleoyl-arachidonoyl-glycerol, (OR 1.07, 95% CI 1.036-1.105, FDR 0.05), and two metabolite ratios, namely spermidine to N-acetylputrescine ratio (OR 0.94, 95% CI 0.903-0.972, FDR 0.09) and benzoate to linoleoyl-arachidonoyl-glycerol ratio (OR 0.87, 95% CI 0.879-0.962, FDR 0.07), were confirmed as having a significant causal relationship with CAD, after correcting for the FDR method (p < 0. 1). A causal relationship was found to be established between beta -hydroxyisovalerylcarnitine and CAD with the validation in other two datasets. Moreover, multiple metabolic pathways were discovered to be associated with CAD. Our study supports the hypothesis that metabolites have an impact on CAD by demonstrating a causal relationship between human metabolites and CAD. This study is important for new strategies for the prevention and treatment of CAD.PMID:39152174 | DOI:10.1038/s41598-024-69879-2

Sci Rep. 2024 Aug 16;14(1):19003. doi: 10.1038/s41598-024-69435-y.ABSTRACTGastric cancer (GC) remains a global disease with a high mortality rate, the lack of effective treatments and the high toxicity of side effects are primary causes for its poor prognosis. Hence, urgent efforts are needed to find safe and effective therapeutic strategies. Gypenoside (Gyp) is a widely used natural product that regulates blood glucose to improve disease progression with few toxic side effects. Given the crucial role of abnormal glycometabolism in driving tumor malignancy, it is important to explore the association between Gyp and glycometabolism in GC and understand the mechanism of action by which Gyp influences glycometabolism. In this study, we demonstrated that Gyp suppresses GC proliferation and migration both in vitro and in vivo. We identified that Gyp suppresses the malignant progression of GC by inhibiting glycolysis using network pharmacology and metabolomics. Transcriptome analysis revealed that the Hippo pathway is a key regulator of glycolysis by Gyp in GC. Furthermore, Gyp induced upregulation of LATS1/2 proteins, leading to increased YAP phosphorylation and decreased TAZ protein expression. The YAP agonist XMU-MP-1 rescued the inhibitory effect of Gyp on GC proliferation by reversing glycolysis. These findings confirmed that Gyp inhibits GC proliferation by targeting glycolysis through the Hippo pathway. Our study examined the role of Gyp in the malignant progression of GC, explored its therapeutic prospects, elucidated a mechanism by which Gyp suppresses GC proliferation through interference with the glycolytic process, thus providing a potential novel therapeutic strategy for GC patients.PMID:39152152 | DOI:10.1038/s41598-024-69435-y

Sci Rep. 2024 Aug 16;14(1):18972. doi: 10.1038/s41598-024-68973-9.ABSTRACTPostmortem metabolomics holds promise for identifying crucial biological markers relevant to death investigations and clinical scenarios. We aimed to assess its applicability in diagnosing hypothermia, a condition lacking definitive biomarkers. Our retrospective analysis involved 1095 postmortem femoral blood samples, including 150 hypothermia cases, 278 matched controls, and 667 randomly selected test cases, analyzed using UHPLC-QTOF mass spectrometry. The model demonstrated robustness with an R2 and Q2 value of 0.73 and 0.68, achieving 94% classification accuracy, 92% sensitivity, and 96% specificity. Discriminative metabolite patterns, including acylcarnitines, stress hormones, and NAD metabolites, along with identified pathways, suggest that metabolomics analysis can be helpful to diagnose fatal hypothermia. Exposure to cold seems to trigger a stress response in the body, increasing cortisol production to maintain core temperature, possibly explaining the observed upregulation of cortisol levels and alterations in metabolic markers related to renal function. In addition, thermogenesis seems to increase metabolism in brown adipose tissue, contributing to changes in nicotinamide metabolism and elevated levels of ketone bodies and acylcarnitines, these findings highlight the effectiveness of UHPLC-QTOF mass spectrometry, multivariate analysis, and pathway identification of postmortem samples in identifying metabolite markers with forensic and clinical significance. The discovered patterns may offer valuable clinical insights and diagnostic markers, emphasizing the broader potential of postmortem metabolomics in understanding critical states or diseases.PMID:39152132 | DOI:10.1038/s41598-024-68973-9

Genome Res. 2024 Aug 16:gr.278756.123. doi: 10.1101/gr.278756.123. Online ahead of print.ABSTRACTNatural selection acts ubiquitously on complex human traits, predominantly constraining the occurrence of extreme phenotypes (stabilizing selection). These constraints propagate to DNA sequence variants associated with traits under selection. The genetic imprints of such evolutionary events can thus be detected via combining effect size estimates from genetic association studies and the corresponding allele frequencies. While this approach has been successfully applied to high-level traits, the prevalence and mode of selection acting on molecular traits remains poorly understood. Here, we estimate the action of natural selection on genetic variants associated with metabolite levels, an important layer of molecular traits. By leveraging summary statistics of published genome-wide association studies with large sample sizes, we find strong evidence of stabilizing selection for 15 out of 97 plasma metabolites. Mendelian randomization analysis revealed that metabolites under stronger stabilizing selection display larger effects on a range of clinically relevant complex traits, suggesting that maintaining a disease-free profile may be an important source of selective constraints on the metabolome. Metabolites under strong stabilizing selection in humans are also more conserved in their concentrations among diverse mammalian species, suggesting shared selective forces across micro and macroevolutionary time scales. Finally, we also found evidence for both disruptive and directional selection on specific lipid metabolites, potentially indicating ongoing evolutionary adaptation in humans. Overall, this study demonstrates that variation in metabolite levels among humans is frequently shaped by natural selection and this may act through their causal impact on disease susceptibility.PMID:39152035 | DOI:10.1101/gr.278756.123

Food Chem Toxicol. 2024 Aug 14:114939. doi: 10.1016/j.fct.2024.114939. Online ahead of print.ABSTRACTAs a replacement for bisphenol A (BPA), bisphenol AF (BPAF) showed stronger maternal transfer and higher fetal accumulation than BPA. Therefore, concerns should be raised about the health risks of maternal exposure to BPAF during gestation on the offspring. In this study, SD rats were exposed to BPAF (0, 50, and 100 mg/kg/day) during gestation to investigate the bioaccumulation and adverse effects in liver, spleen, and kidney tissues of the offspring at weaning period. Bioaccumulation of BPAF in these tissues with concentrations ranging from 1.56 ng/mg (in spleen of males) to 55.44 ng/mg (in liver of females) led to adverse effects at different biological levels, including increased relative weights of spleen and kidneys, histopathological damage in liver, spleen, and kidney, organ functional damage in liver, spleen, and kidney, upregulated expression of genes related to lipid metabolism (in liver), oxidative stress response (in kidney), immunity and inflammatory (in spleen). Furthermore, dysregulated metabolomics was identified in spleen, with 217 differential metabolites screened and 9 KEGG pathways significantly enriched. This study provides a comprehensive insight into the systemic toxicities of prenatal exposure to BPAF in SD rats. Given the broad applications and widespread occurrence of BPAF, its safety should be re-considered.PMID:39151878 | DOI:10.1016/j.fct.2024.114939

Food Chem Toxicol. 2024 Aug 14:114935. doi: 10.1016/j.fct.2024.114935. Online ahead of print.ABSTRACTSodium nitrite (SN), a prevalent food preservative, is known to precipitate hepatotoxicity upon exposure. This study elucidates the hepatoprotective effects of corn oligopeptide (COP) and vitamin E (VE) against SN-induced hepatic injury in canine hepatocytes. Canine liver cells were subjected to SN to induce hepatotoxicity, followed by treatment with COP and VE. Evaluations included assays for cell viability, oxidative stress markers, apoptosis, and inflammatory cytokines. Additionally, transcriptomic and metabolomic analyses were performed to delineate the underlying molecular mechanisms. The findings demonstrated that COP and VE significantly ameliorated SN-induced cytotoxicity, oxidative stress, and apoptosis. It was evidenced by restored cell viability, enhanced antioxidant enzyme activity, reduced cytoplasmic enzyme leakage, and decreased levels of malondialdehyde and inflammatory cytokines, with COP showing superior efficacy. The RNA sequencing revealed that COP treatment suppressed the SN-activated aminoacyl-tRNA biosynthesis pathway and TGF-β/NF-κB signaling pathways, thereby mitigating amino acid depletion, apoptosis, and inflammation. Moreover, COP treatment upregulated genes associated with protein folding, bile acid synthesis, and DNA repair. Metabolomic analysis corroborated these results, showing that COP restored amino acid levels and enhanced bile acid metabolism, alleviating SN-induced metabolic disruptions. These findings offered significant insights into the protective mechanisms of COP underscoring its prospective application in treating liver injuries.PMID:39151875 | DOI:10.1016/j.fct.2024.114935

Int J Biol Macromol. 2024 Aug 14:134782. doi: 10.1016/j.ijbiomac.2024.134782. Online ahead of print.ABSTRACTHyperuricemia (HUA) is one of the most common chronic diseases today, with a prevalence exceeding 14 % in both the United States and China. Current clinical treatments for HUA focus on promoting uric acid (UA) excretion and inhibiting UA production, but often neglect the strain on the liver and kidneys. The fruit of Alpinia oxyphylla (A. oxyphylla) is known to improve renal function, regulate metabolism, and exhibit anti-inflammatory effects; however, its effectiveness and mechanisms in treating HUA are not well understood. In this study, HUA mice induced by potassium oxonate and adenine were treated with A. oxyphylla polysaccharide (AFP) for 21 days. The levels associated with HUA were quantified using assay kits to evaluate the impact of AFP on HUA. Serum metabolomics and 16S rRNA sequencing were used to investigate the mechanisms by which AFP ameliorates HUA. The results showed that AFP treatment reduced abnormal biochemical levels, including UA, blood urea nitrogen, and creatinine, in HUA mice. AFP inhibited UA synthesis by regulating pyrimidine metabolism and the metabolism of alanine, aspartate and glutamate, reduced kidney inflammation, and promoted UA excretion by regulating intestinal flora. Thus, AFP appears to be an effective agent for alleviating HUA symptoms.PMID:39151857 | DOI:10.1016/j.ijbiomac.2024.134782

J Biol Chem. 2024 Aug 14:107677. doi: 10.1016/j.jbc.2024.107677. Online ahead of print.ABSTRACTThe tricarboxylic acid (TCA) cycle plays a crucial role in mitochondrial ATP production in the healthy heart. However, in heart failure, the TCA cycle becomes dysregulated. Understanding the mechanism by which TCA cycle genes are transcribed in the healthy heart is an important prerequisite to understanding how these genes become dysregulated in the failing heart. PGC-1α is a transcriptional coactivator that broadly induces genes involved in mitochondrial ATP production. PGC-1α potentiates its effects through coactivation of coupled transcription factors, such as ERR, Nrf1, Gabpa, and YY1. We hypothesized that PGC-1α plays an essential role in transcription of TCA cycle genes. Thus, by utilizing localization peaks of PGC-1α to TCA cycle gene promoters, it would allow the identification of coupled transcription factors. PGC-1α potentiated the transcription of 13 out of 14 TCA cycle genes, partly through ERR, Nrf1, Gabpa, and YY1. ChIP-sequencing showed PGC-1α localization peaks in TCA cycle gene promoters. Transcription factors with binding elements that were found proximal to PGC-1α peak localization were generally essential for transcription of the gene. These transcription factor binding elements were well conserved between mice and humans. Among the four transcription factors, ERR and Gabpa played a major role in potentiating transcription when compared to Nrf1 and YY1. These transcription factor-dependent PGC-1α recruitment was verified with Idh3a, Idh3g, and Sdha promoters with DNA binding assay. Taken together, this study clarifies the mechanism by which TCA cycle genes are transcribed, which could be useful to understand how those genes are dysregulated in pathological conditions.PMID:39151728 | DOI:10.1016/j.jbc.2024.107677

Sci Total Environ. 2024 Aug 14:175542. doi: 10.1016/j.scitotenv.2024.175542. Online ahead of print.ABSTRACTOBJECTIVE: This study aimed to investigate the influence of exposure to ambient fine particulate matter (PM2.5) and its components during pregnancy on the prevalence of preterm birth (PTB). Additionally, we sought to identify the susceptible exposure window. Furthermore, we explored the potential mediating role of blood analysis and a comprehensive metabolic panel in the association between pollutant exposure and PTB incidence.METHODS: This birth cohort study recruited 139 participants with PTB outcomes and 1713 controls from Fujian Maternal and Child Health Hospital between January 2021 and June 2023. Sociodemographic characteristics and clinical treatment data during participants' first pregnancies were collected. The exposure levels to pollutants during pregnancy were estimated via a combined geographic-statistical model utilising satellite remote sensing data. The distributional lag nonlinear modelling was employed to assess associations between pollutant exposure during pregnancy and the prevalence of PTB. Weighted quantile regression was used to identify key components associated with PM2.5 and PTB during pregnancy. Additionally, a mediating effect analysis was conducted to evaluate the role of blood analysis. The metabolic profile was used to screen for differentially abundant metabolites associated with PTB and explore their relative expression in relation to air pollutants and PTB incidence.RESULTS: Following the adjustment for potential confounding variables, the mean weekly susceptibility windows for PM2.5 were identified as 7-10, 16-19, and 22-28 weeks; 8-10, and 15-19 weeks for inorganic sulfate; 6-10, and 15-28 weeks for nitrate; 6-12, and 15-28 weeks for ammonium (NH4+); and 7-9, 18-20, and 22-36 weeks for organic matter. During mixed exposure to PM2.5 components, the key component is NH4+. In the mixed exposure to PM2.5 components, NH4+ emerged as a key contributor. The results of the mediation analysis revealed that haemoglobin played a mediating role, accounting for 21.53 % of the association between exposure to environmental pollutants and the prevalence of PTB. It is noteworthy that, no mediating effects were observed for the other variables. Furthermore, non-targeted metabolomics identified 17 metabolites associated with PTB. Among these factors, hydrogen phosphate may impact metabolic pathways such as oxidative phosphorylation, influencing the risk of PTB. The interplay between environmental pollutants and metabolites, particularly through oxidative phosphorylation pathways, may contribute to PTB incidence.CONCLUSIONS: The evidence indicates that exposure to PM2.5 and its components during pregnancy were a significant risk factor for PTB. Notably, specific weekly exposure windows were identified for pollutants during pregnancy. Among the PM2.5 components, NH4+ exhibited the most substantial weight in the association analysis between exposure to the mixture of components and PTB. Furthermore, our mediation analysis revealed that haemoglobin serves as a partial mediator in the relationship between exposure to pollutants during pregnancy and the prevalence of PTB. Additionally, maternal serum metabolic profiles differed between the preterm and control groups. Notably, a combined effect involving hydrogen phosphate and mixed exposure to PM2.5 fractions further contributed to the development of PTB. Oxidative phosphorylation pathways may play pivotal roles in this intricate association.PMID:39151621 | DOI:10.1016/j.scitotenv.2024.175542

J Lipid Res. 2024 Aug 14:100621. doi: 10.1016/j.jlr.2024.100621. Online ahead of print.ABSTRACTThe rapid increase in lipidomic studies has led to a collaborative effort within the community to establish standards and criteria for producing, documenting, and disseminating data. Creating a dynamic easy-to-use checklist that condenses key information about lipidomic experiments into common terminology will enhance the field's consistency, comparability, and repeatability. Here, we describe the structure and rationale of the established Lipidomics Minimal Reporting Checklist to increase transparency in lipidomics research.PMID:39151590 | DOI:10.1016/j.jlr.2024.100621

Bioresour Technol. 2024 Aug 14:131241. doi: 10.1016/j.biortech.2024.131241. Online ahead of print.ABSTRACTThe current study investigated the effect of iron oxide nanoparticles (IONPs) on mixotrophic microalgae cultivation in wastewater for biofuel production. Optimal IONPs doses of 10 and 20 mg/L increased Chlorella pyrenoidosa growth by 16 % and lipid accumulation by 53 %, respectively, compared with the control group. Conversely, the protein content declined drastically, while carbohydrates remained relatively unchanged. A maximum of 15 % rise in biomass growth was observed for Chlorella sorokiniana IITRF at an IONPs dose of 20 mg/L, with no significant variation in biochemical composition. Microalgae grown under mixotrophic conditions with IONPs in a biofilm reactor were more suitable for biogas production than biodiesel, increasing biogas and methane content by 38 and 48 %, respectively. The findings suggest that low doses of IONPs can enhance microalgal biomass, biogas production and methane content. Further metabolomics studies are warranted to investigate the interaction between microalgae and nanoparticles to achieve high-quality biodiesel.PMID:39151571 | DOI:10.1016/j.biortech.2024.131241