PubMed

Front Nutr. 2024 Mar 18;11:1335538. doi: 10.3389/fnut.2024.1335538. eCollection 2024.ABSTRACTThe Chinese name "Lingzhi" refers to Ganoderma genus, which are increasingly used in the food and medical industries. Ganoderma species are often used interchangeably since the differences in their composition are not known. To find compositional metabolite differences among Ganoderma species, we conducted a widely targeted metabolomics analysis of four commonly used edible and medicinal Ganoderma species based on ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Through pairwise comparisons, we identified 575-764 significant differential metabolites among the species, most of which exhibited large fold differences. We screened and analyzed the composition and functionality of the advantageous metabolites in each species. Ganoderma lingzhi advantageous metabolites were mostly related to amino acids and derivatives, as well as terpenes, G. sinense to terpenes, and G. leucocontextum and G. tsugae to nucleotides and derivatives, alkaloids, and lipids. Network pharmacological analysis showed that SRC, GAPDH, TNF, and AKT1 were the key targets of high-degree advantage metabolites among the four Ganoderma species. Analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes demonstrated that the advantage metabolites in the four Ganoderma species may regulate and participate in signaling pathways associated with diverse cancers, Alzheimer's disease, and diabetes. Our findings contribute to more targeted development of Ganoderma products in the food and medical industries.PMID:38562486 | PMC:PMC10982346 | DOI:10.3389/fnut.2024.1335538

Food Chem X. 2024 Mar 15;22:101286. doi: 10.1016/j.fochx.2024.101286. eCollection 2024 Jun 30.ABSTRACTUPLC-Q-TOF-MS and electronic tongue analysis were applied to analyse the metabolic profile and taste quality of Yunnan Arabica coffee under seven primary processing methods. The total phenolic content ranged from 34.44 to 44.42 mg/g DW, the e-tongue results revealed the strongest umami sensor response value in the sample prepared with traditional dry processing, while the samples prepared via honey processing II had the strongest astringency sensor response value. Metabolomics analysis identified 221 differential metabolites, with higher contents of amino acids and derivatives within dry processing II sample, and increased contents of lipids and phenolic acids in the honey processing III sample. The astringency and aftertaste-astringency of the coffee samples positively correlated with the trigonelline, 3,5-di-caffeoylquinic acid and 4-caffeoylquinic acid content. The results contributed to a better understanding of how the primary processing process affects coffee quality, and supply useful information for the enrichment of coffee biochemistry theory.PMID:38562182 | PMC:PMC10982556 | DOI:10.1016/j.fochx.2024.101286

Front Cell Dev Biol. 2024 Mar 18;12:1395922. doi: 10.3389/fcell.2024.1395922. eCollection 2024.NO ABSTRACTPMID:38562142 | PMC:PMC10982473 | DOI:10.3389/fcell.2024.1395922

J Agric Food Chem. 2024 Apr 1. doi: 10.1021/acs.jafc.3c09005. Online ahead of print.ABSTRACTThis study compares the inhibitory effects of orange peel polar fraction (OPP) and orange peel nonpolar fraction (OPNP) on trimethylamine (TMA) and trimethylamine N-oxide (TMAO) production in response to l-carnitine treatment in vivo and in vitro. Metabolomics is used to identify bioactive compounds. The research demonstrates that the OPP effectively regulates atherosclerosis-related markers, TMA and TMAO in plasma and urine, compared to the OPNP. Our investigation reveals that these inhibitory effects are independent of changes in gut microbiota composition. The effects are attributed to the modulation of cntA/B enzyme activity and FMO3 mRNA expression in vitro. Moreover, OPP exhibits stronger inhibitory effects on TMA production than OPNP, potentially due to its higher content of feruloylputrescine, which displays the highest inhibitory activity on the cntA/B enzyme and TMA production. These findings suggest that the OPP containing feruloylputrescine has the potential to alleviate cardiovascular diseases by modulating cntA/B and FMO3 enzymes without directly influencing gut microbiota composition.PMID:38562057 | DOI:10.1021/acs.jafc.3c09005

Plant Physiol. 2024 Apr 2:kiae195. doi: 10.1093/plphys/kiae195. Online ahead of print.ABSTRACTFruit ripening is a complex process involving dynamic changes to metabolites and is controlled by multiple factors, including transcription factors (TFs). Several TFs are reportedly essential regulators of tomato (Solanum lycopersicum) fruit ripening. To evaluate the effects of specific TFs on metabolite accumulation during fruit ripening, we combined CRISPR/Cas9-mediated mutagenesis with metabolome and transcriptome analyses to explore regulatory mechanisms. Specifically, we generated various genetically engineered tomato lines that differed regarding metabolite contents and fruit colors. The metabolite and transcript profiles indicated that the selected TFs have distinct functions that control fruit metabolite contents, especially carotenoids and sugars. Moreover, a mutation to ELONGATED HYPOCOTYL5 (HY5) increased tomato fruit fructose and glucose contents by approximately 20% (relative to the wild-type levels). Our in vitro assay showed that HY5 can bind directly to the G-box cis-element in the Sugars Will Eventually be Exported Transporter (SWEET12c) promoter to activate expression, thereby modulating sugar transport. Our findings provide insights into the mechanisms regulating tomato fruit ripening and metabolic networks, providing the theoretical basis for breeding horticultural crops that produce fruit with diverse flavors and colors.PMID:38561990 | DOI:10.1093/plphys/kiae195

Ann Rheum Dis. 2024 Apr 1:ard-2023-224839. doi: 10.1136/ard-2023-224839. Online ahead of print.ABSTRACTOBJECTIVES: A timely diagnosis is imperative for curing cancer. However, in patients with rheumatic musculoskeletal diseases (RMDs) or paraneoplastic syndromes, misleading symptoms frequently delay cancer diagnosis. As metabolic remodelling characterises both cancer and RMD, we analysed if a metabolic signature can indicate paraneoplasia (PN) or reveal concomitant cancer in patients with RMD.METHODS: Metabolic alterations in the sera of rheumatoid arthritis (RA) patients with (n=56) or without (n=52) a history of invasive cancer were quantified by nuclear magnetic resonance analysis. Metabolites indicative of cancer were determined by multivariable regression analyses. Two independent RA and spondyloarthritis (SpA) cohorts with or without a history of invasive cancer were used for blinded validation. Samples from patients with active cancer or cancer treatment, pulmonary and lymphoid type cancers, paraneoplastic syndromes, non-invasive (NI) precancerous lesions and non-melanoma skin cancer and systemic lupus erythematosus and samples prior to the development of malignancy were used to test the model performance.RESULTS: Based on the concentrations of acetate, creatine, glycine, formate and the lipid ratio L1/L6, a diagnostic model yielded a high sensitivity and specificity for cancer diagnosis with AUC=0.995 in the model cohort, AUC=0.940 in the blinded RA validation cohort and AUC=0.928 in the mixed RA/SpA cohort. It was equally capable of identifying cancer in patients with PN. The model was insensitive to common demographic or clinical confounders or the presence of NI malignancy like non-melanoma skin cancer.CONCLUSIONS: This new set of metabolic markers reliably predicts the presence of cancer in arthritis or PN patients with high sensitivity and specificity and has the potential to facilitate a rapid and correct diagnosis of malignancy.PMID:38561219 | DOI:10.1136/ard-2023-224839

Chemosphere. 2024 Mar 30:141836. doi: 10.1016/j.chemosphere.2024.141836. Online ahead of print.ABSTRACTThe biological synthesis of silver nanoparticles (Ag-NPs) with fungi has shown promising results in antibacterial and antioxidant properties. Fungi generate metabolites (both primary and secondary) and proteins, which aid in the formation of metal nanoparticles as reducing or capping agents. While several studies have been conducted on the biological production of Ag-NPs, the exact mechanisms still need to be clarified. In this study, Ag-NPs are synthesized greenly using an unstudied fungal strain, Sarocladium subulatum AS4D. Three silver salts were used to synthesize the Ag-NPs for the first time, optimized using a cell-free extract (CFE) strategy. Additionally, these NPs were assessed for their antimicrobial and antioxidant properties. Various spectroscopic and microscopy techniques were utilized to confirm Ag-NP formation and analyze their morphology, crystalline properties, functional groups, size, stability, and concentrations. Untargeted metabolomics and proteome disruption were employed to explore the synthesis mechanism. Computational tools were applied to predict metabolite toxicity and antibacterial activity. The study identified 40 fungal metabolites capable of reducing silver ions, with COOH and OH functional groups playing a pivotal role. The silver salt type impacted the NPs' size and stability, with sizes ranging from 40 to 52 nm and zeta potentials from -0.9 to -30.4 mV. Proteome disruption affected size and stability but not shape. Biosynthesized Ag-NPs using protein-free extracts ranged from 55 to 62 nm, and zeta potentials varied from -18 to -27 mV. Molecular docking studies and PASS results found no role for the metabolome in antibacterial activity. This suggests the antibacterial activity comes from Ag-NPs, not capping or reducing agents. Overall, the research affirmed the vital role of specific reducing metabolites in the biosynthesis of Ag-NPs, while proteins derived from biological extracts were found to solely affect their size and stability.PMID:38561160 | DOI:10.1016/j.chemosphere.2024.141836

Food Chem Toxicol. 2024 Mar 30:114627. doi: 10.1016/j.fct.2024.114627. Online ahead of print.ABSTRACTTestes are very prone to be damaged by environmental pollutants, but there is a lack of information about the impact of "chemical cocktails" (CC) on the testicular metabolome and the possible influence in the gut-gonad crosstalk. For this, BALB/c mice were given flumequine and diclofenac orally in food and potentially toxic trace elements (Cd, Hg, As) in drinking water. A mice group was supplemented with selenium, a well-known antagonist against many pollutants. Our results revealed that the steroid 5-alpha-androstan-17-beta-ol propionate, suggested as a parameter of androgenicity independent of testosterone levels, proline that improves reproductive indicators in male rabbits affected by environmental stress) among others metabolites are only present after CC exposure with rodent and selenium supplemented diet. Selenium also antagonized the up-or down-regulation of anandamide (20:l, n-9) (p < 0.001 and FC 0.54 of CC vs C but p > 0,05 and FC 0.74 of CC-Se vs C), that regulates gonadotropin-releasing hormones in mammals, 2,3-dinor-11b-PGF2a (p < 0.001 and FC 0.12 of CC vs C but p > 0,05 and FC 0.34 of CC-Se vs C), which has been related with reproductive hormones, besides others testicular metabolites altered by the exposure to the CC and reversed the levels to control. Moreover, numerous significant associations between gut microbes and testicular metabolites indicated a possible impact of pollutants in the testes mediated by gut microbiota due to a gut-gonad crosstalk.PMID:38561037 | DOI:10.1016/j.fct.2024.114627

Eur J Nucl Med Mol Imaging. 2024 Apr 2. doi: 10.1007/s00259-024-06688-9. Online ahead of print.ABSTRACTBACKGROUND: Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose 131I therapy, the alterations and regulatory mechanisms dependent on intestinal microecology remain poorly understood. We aimed to identify the characteristics of the gut microbiota and metabolites in DTC patients suffering from high-dose 131I therapy and explore the radioprotective mechanisms underlying arachidonic acid (ARA) treatment.METHODS: A total of 102 patients with DTC were recruited, with fecal samples collected before and after 131I therapy for microbiome and untargeted and targeted metabolomic analyses. Mice were exposed to total body irradiation with ARA replenishment and antibiotic pretreatment and were subjected to metagenomic, metabolomic, and proteomic analyses.RESULTS: 131I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after 131I treatment, and metabolites with decreased levels and pathways related to ARA and linoleic acid were observed. In an irradiation mouse model, ARA supplementation not only improved quality of life and recovered hematopoietic and gastrointestinal systems but also ameliorated oxidative stress and inflammation and preserved enteric microecology composition. Additionally, antibiotic intervention eliminated the radioprotective effects of ARA. Proteomic analysis and ursolic acid pretreatment showed that ARA therapy greatly influenced intestinal lipid metabolism in mice subjected to irradiation by upregulating the expression of hydroxy-3-methylglutaryl-coenzyme A synthase 1.CONCLUSION: These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects.PMID:38561516 | DOI:10.1007/s00259-024-06688-9

J Agric Food Chem. 2024 Apr 1. doi: 10.1021/acs.jafc.4c00421. Online ahead of print.ABSTRACTZearalenone (ZEN) is a mycotoxin that is harmful to humans and animals. In this study, female and male rats were exposed to ZEN, and the results showed that ZEN reduced the farnesoid X receptor (FXR) expression levels in the liver and disrupted the enterohepatic circulation of bile acids (BAs). A decrease in food intake induced by ZEN was negatively correlated with an increase in the level of total BAs. BA-targeted metabolomics revealed that ZEN increased glycochenodeoxycholic acid levels and decreased the ratio of conjugated BAs to unconjugated BAs, which further increased the hypothalamic FXR expression levels. Preventing the increase in total BA levels induced by ZEN via Lactobacillus rhamnosus GG intervention restored the appetite. In conclusion, ZEN disrupted the enterohepatic circulation of BAs to decrease the level of food intake. This study reveals a possible mechanism by which ZEN affects food intake and provides a new approach to decrease the toxic effects of ZEN.PMID:38560889 | DOI:10.1021/acs.jafc.4c00421

Microbiologyopen. 2024 Apr;13(2):e1408. doi: 10.1002/mbo3.1408.ABSTRACTArginine-ornithine metabolism plays a crucial role in bacterial homeostasis, as evidenced by numerous studies. However, the utilization of arginine and the downstream products of its metabolism remain undefined in various gut bacteria. To bridge this knowledge gap, we employed genomic screening to pinpoint relevant metabolic targets. We also devised a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics method to measure the levels of arginine, its upstream precursors, and downstream products in cell-free conditioned media from enteric pathobionts, including Escherichia coli, Klebsiella aerogenes, K. pneumoniae, Pseudomonas fluorescens, Acinetobacter baumannii, Streptococcus agalactiae, Staphylococcus epidermidis, S. aureus, and Enterococcus faecalis. Our findings revealed that all selected bacterial strains consumed glutamine, glutamate, and arginine, and produced citrulline, ornithine, and GABA in our chemically defined medium. Additionally, E. coli, K. pneumoniae, K. aerogenes, and P. fluorescens were found to convert arginine to agmatine and produce putrescine. Interestingly, arginine supplementation promoted biofilm formation in K. pneumoniae, while ornithine supplementation enhanced biofilm formation in S. epidermidis. These findings offer a comprehensive insight into arginine-ornithine metabolism in enteric pathobionts.PMID:38560776 | DOI:10.1002/mbo3.1408

ArXiv [Preprint]. 2024 Mar 11:arXiv:2403.07147v1.ABSTRACTAutism spectrum disorder (ASD) is a complex neurodevelopmental condition with a wide range of behavioral and cognitive impairments. While genetic and environmental factors are known to contribute to its etiology, the underlying metabolic perturbations associated with ASD which can potentially connect genetic and environmental factors, remain poorly understood. Therefore, we conducted a metabolomic case-control study and performed a comprehensive analysis to identify significant alterations in metabolite profiles between children with ASD and typically developing (TD) controls. The objective of this study is to elucidate potential metabolomic signatures associated with ASD in children and identify specific metabolites that may serve as biomarkers for the disorder. We conducted metabolomic profiling on plasma samples from participants in the second phase of Epidemiological Research on Autism in Jamaica, a cohort of 200 children with ASD and 200 TD controls (2-8 years old). Using high-throughput liquid chromatography-mass spectrometry techniques, we performed a targeted metabolite analysis, encompassing amino acids, lipids, carbohydrates, and other key metabolic compounds. After quality control and imputation of missing values, we performed univariable and multivariable analysis using normalized metabolites while adjusting for covariates, age, sex, socioeconomic status, and child's parish of birth. Our findings revealed unique metabolic patterns in children with ASD for four metabolites compared to TD controls. Notably, three of these metabolites were fatty acids, including myristoleic acid, eicosatetraenoic acid, and octadecenoic acid. Additionally, the amino acid sarcosine exhibited a significant association with ASD. These findings highlight the role of metabolites in the etiology of ASD and suggest opportunities for the development of targeted interventions.PMID:38560734 | PMC:PMC10980079

Front Mol Biosci. 2024 Mar 15;11:1376345. doi: 10.3389/fmolb.2024.1376345. eCollection 2024.ABSTRACTINTRODUCTION: Danggui Buxue Decoction (DBD) is a clinically proven, effective, classical traditional Chinese medicine (TCM) formula for treating blood deficiency syndrome (BDS). However, its effects and effective constituents in the treatment of BDS remain unclear, limiting precise clinical therapy and quality control. This study aimed to accurately evaluate the effects of DBD and identify its effective constituents and quality markers.METHODS: BDS was induced in rats by a combined injection of acetylphenylhydrazine and cyclophosphamide, and the efficacy of DBD against BDS was evaluated based on body weight, body temperature, energy metabolism, general status, visceral indices, histopathology, biochemical markers, and metabolomics. The effects of DBD on urinary and serum biomarkers of BDS were investigated, and the associated metabolic pathways were analyzed via metabolomics. Guided by Chinmedomics, the effective constituents and quality markers of DBD were identified by analyzing the dynamic links between metabolic biomarkers and effective constituents in vivo.RESULTS: DBD improved energy metabolism, restored peripheral blood and serum biochemical indices, and meliorated tissue damage in rats with BDS. Correlation analyses between biochemical indices and biomarkers showed that 15(S)-HPETE, LTB4, and taurine were core biomakers and that arachidonic acid, taurine, and hypotaurine metabolism were core metabolic pathways regulated by DBD. Calycosin-7-glucoside, coumarin, ferulic acid sulfate, cycloastragenol, (Z)-ligustilide + O, astragaloside IV, acetylastragaloside I, and linoleic acid were identified as effective constituents improving the hematopoietic function of the rats in the BDS model. Additionally, calycosin-7-glucoside, ferulic acid, ligustilide, and astragaloside IV were identified as quality markers of DBD.CONCLUSION: The hematopoietic function of DBD was confirmed through analysis of energy metabolism, biochemical markers, histopathology, and metabolomics. Moreover, by elucidating effective constituents of DBD in BDS treatment, quality markers were confirmed using a Chinmedomics strategy. These results strengthen the quality management of DBD and will facilitate drug innovation.PMID:38560521 | PMC:PMC10978583 | DOI:10.3389/fmolb.2024.1376345

Front Mol Biosci. 2024 Mar 15;11:1253983. doi: 10.3389/fmolb.2024.1253983. eCollection 2024.ABSTRACTTuberculous meningitis (TBM) is a severe form of tuberculosis with high neuro-morbidity and mortality, especially among the paediatric population (aged ≤12 years). Little is known of the associated metabolic changes. This study aimed to identify characteristic metabolic markers that differentiate severe cases of paediatric TBM from controls, through non-invasive urine collection. Urine samples selected for this study were from two paediatric groups. Group 1: controls (n = 44): children without meningitis, no neurological symptoms and from the same geographical region as group 2. Group 2: TBM cases (n = 13): collected from paediatric patients that were admitted to Tygerberg Hospital in South Africa on the suspicion of TBM, mostly severely ill; with a later confirmation of TBM. Untargeted 1H NMR-based metabolomics data of urine were generated, followed by statistical analyses via MetaboAnalyst (v5.0), and the identification of important metabolites. Twenty nine urinary metabolites were identified as characteristic of advanced TBM and categorized in terms of six dysregulated metabolic pathways: 1) upregulated tryptophan catabolism linked to an altered vitamin B metabolism; 2) perturbation of amino acid metabolism; 3) increased energy production-metabolic burst; 4) disrupted gut microbiota metabolism; 5) ketoacidosis; 6) increased nitrogen excretion. We also provide original biological insights into this biosignature of urinary metabolites that can be used to characterize paediatric TBM patients in a South African cohort.PMID:38560518 | PMC:PMC10978807 | DOI:10.3389/fmolb.2024.1253983

Genes Dis. 2023 Sep 7;11(4):101079. doi: 10.1016/j.gendis.2023.101079. eCollection 2024 Jul.ABSTRACTCYP3A5 is a cytochrome P450 (CYP) enzyme that metabolizes drugs and contributes to drug resistance in cancer. However, it remains unclear whether CYP3A5 directly influences cancer progression. In this report, we demonstrate that CYP3A5 regulates glucose metabolism in pancreatic ductal adenocarcinoma. Multi-omics analysis showed that CYP3A5 knockdown results in a decrease in various glucose-related metabolites through its effect on glucose transport. A mechanistic study revealed that CYP3A5 enriches the glucose transporter GLUT1 at the plasma membrane by restricting the translation of TXNIP, a negative regulator of GLUT1. Notably, CYP3A5-generated reactive oxygen species were proved to be responsible for attenuating the AKT-4EBP1-TXNIP signaling pathway. CYP3A5 contributes to cell migration by maintaining high glucose uptake in pancreatic cancer. Taken together, our results, for the first time, reveal a role of CYP3A5 in glucose metabolism in pancreatic ductal adenocarcinoma and identify a novel mechanism that is a potential therapeutic target.PMID:38560501 | PMC:PMC10980945 | DOI:10.1016/j.gendis.2023.101079

Therap Adv Gastroenterol. 2024 Mar 29;17:17562848241239580. doi: 10.1177/17562848241239580. eCollection 2024.ABSTRACTBACKGROUND: Despite numerous metabolomic studies on ulcerative colitis (UC), the results have been highly variable, making it challenging to identify key metabolic abnormalities in UC.OBJECTIVES: This study aims to uncover key metabolites and metabolic pathways in UC by analyzing existing metabolomics data.DESIGN: A systematic review.DATA SOURCES AND METHODS: We conducted a comprehensive search in databases (PubMed, Cochrane Library, Embase, and Web of Science) and relevant study references for metabolomic research on UC up to 28 December 2022. Significant metabolite differences between UC patients and controls were identified, followed by an analysis of relevant metabolic pathways.RESULTS: This review incorporated 78 studies, identifying 2868 differentially expressed metabolites between UC patients and controls. The metabolites were predominantly from 'lipids and lipid-like molecules' and 'organic acids and derivatives' superclasses. We found 101 metabolites consistently altered in multiple datasets within the same sample type and 78 metabolites common across different sample types. Of these, 62 metabolites exhibited consistent regulatory trends across various datasets or sample types. Pathway analysis revealed 22 significantly altered metabolic pathways, with 6 pathways being recurrently enriched across different sample types.CONCLUSION: This study elucidates key metabolic characteristics in UC, offering insights into molecular mechanisms and biomarker discovery for the disease. Future research could focus on validating these findings and exploring their clinical applications.PMID:38560428 | PMC:PMC10981261 | DOI:10.1177/17562848241239580

Front Pharmacol. 2024 Mar 15;15:1333167. doi: 10.3389/fphar.2024.1333167. eCollection 2024.ABSTRACTBackground: ZhuRiHeng Drop Pill (ZRH) is a traditional Mongolian medicinal preparation. Despite its long history of use for the treatment of coronary heart disease, there have been few toxicological studies of the safety profile of ZRH. Purpose: In order to comprehensively elucidate the underlying mechanisms behind the observed toxicity of ZRH on rat livers in the 180-day repeated oral toxicity study, we conducted a comprehensive analysis by integrating transcriptomic and metabolomic data. Methods: High-resolution mass spectrometry was conducted to evaluate the constituents of ZRH. For the acute oral toxicity study, mice were administered a dose of 32 g/(kg·d) of ZRH, while rats were instead orally administered 0.934, 1.868, or 3.736 g/(kg·d) of ZRH over a 180-day period in a 180-day repeated oral toxicity study. Conventional index and organ weights/histology were then monitored to detect any potential ZRH treatment-related toxicity. To identify key genes and metabolites involved in ZRH toxicological processes, we performed transcriptomic and metabolomic analyses of liver tissue upon ZRH treatment using RNA-seq techniques, qPCR and liquid chromatography-mass spectrometry analyses. Results: A total of 60 compounds in ZRH were identified and speculated in positive and negative ion modes. Mice in the acute toxicity study exhibited no signs of ZRH-related toxicity. In a protracted oral toxicity investigation spanning 180 days, discernible elevations in liver ratios were noted in both male and female rats across all three dose cohorts, relative to the control group (p < 0.05 or p < 0.01). Upon subjecting to ZRH treatment, our transcriptomic and qPCR analyses unveiled notable upregulation of crucial genes, exemplified by Abcb1b and Cyp2b2, known for theirs involvement in liver drug transport and metabolism function. Furthermore, our untargeted metabolomic analysis provided supplementary insights, revealing significant regulation in pyrimidine metabolism, as well as alanine, aspartate, and glutamate metabolism pathways. Conclusion: Our study unveils a panoramic understanding of the temporal, dosage-specific, and gene dimensions surrounding the metabolic and transcriptional shifts induced by ZRH exposure. As we peer into the future, recommendations emerge for further exploration, encompassing aspects such as time dynamics, dosage considerations, and gene-centric avenues to enhance therapeutic efficacy.PMID:38560353 | PMC:PMC10978746 | DOI:10.3389/fphar.2024.1333167

Comput Struct Biotechnol J. 2024 Mar 19;23:1274-1287. doi: 10.1016/j.csbj.2024.03.016. eCollection 2024 Dec.ABSTRACTOBJECTIVE: Classification tasks are an open challenge in the field of biomedicine. While several machine-learning techniques exist to accomplish this objective, several peculiarities associated with biomedical data, especially when it comes to omics measurements, prevent their use or good performance achievements. Omics approaches aim to understand a complex biological system through systematic analysis of its content at the molecular level. On the other hand, omics data are heterogeneous, sparse and affected by the classical "curse of dimensionality" problem, i.e. having much fewer observation, samples (n) than omics features (p). Furthermore, a major problem with multi-omics data is the imbalance either at the class or feature level. The objective of this work is to study whether feature extraction and/or feature selection techniques can improve the performances of classification machine-learning algorithms on omics measurements.METHODS: Among all omics, metabolomics has emerged as a powerful tool in cancer research, facilitating a deeper understanding of the complex metabolic landscape associated with tumorigenesis and tumor progression. Thus, we selected three publicly available metabolomics datasets, and we applied several feature extraction techniques both linear and non-linear, coupled or not with feature selection methods, and evaluated the performances regarding patient classification in the different configurations for the three datasets.RESULTS: We provide general workflow and guidelines on when to use those techniques depending on the characteristics of the data available. To further test the extension of our approach to other omics data, we have included a transcriptomics and a proteomics data. Overall, for all datasets, we showed that applying supervised feature selection improves the performances of feature extraction methods for classification purposes. Scripts used to perform all analyses are available at: https://github.com/Plant-Net/Metabolomic_project/.PMID:38560281 | PMC:PMC10979063 | DOI:10.1016/j.csbj.2024.03.016

Heliyon. 2024 Mar 20;10(7):e28450. doi: 10.1016/j.heliyon.2024.e28450. eCollection 2024 Apr 15.ABSTRACTFermentation is an effective means of enhancing the nutritional value of natural medicines, however, it is unclear how the metabolites changed during the fermentation of Paeonia lactiflora root (PLR). This study intends to elucidate how the active constituents and antioxidant activity of PLR change during fermentation. The study examined the levels of total glucosides of paeony (TGP), total flavonoids content (TFC), total phenols content (TPC), and antioxidant capability by high performance liquid chromatography (HPLC) and spectrophotometry. The chemical compositions before and after PLR fermentation were compared utilizing ultra-high performance liquid chromatography-mass spectrometry (UHPLC - MS). The findings from this study indicate that TGP, TFC and TPC peaked at Day 2 of fermentation, and the antioxidant capacity increased after fermentation. Of the 109 detected compounds, 18 were discrepant compounds. In summary, fermentation is an essential strategy for enhancing the functional activity of PLR. The current study could establish a scientific basis for future research on the fermentation of PLR, and provides new insights into the influence of fermentation on chemical composition as well as the antioxidant activity of drugs.PMID:38560231 | PMC:PMC10981120 | DOI:10.1016/j.heliyon.2024.e28450

Heliyon. 2024 Mar 16;10(7):e28027. doi: 10.1016/j.heliyon.2024.e28027. eCollection 2024 Apr 15.ABSTRACTChronic cerebral ischemia hypoperfusion plays a role in the initiation and progression of vascular dementia, which causes changes in metabolites. Currently, there is no standard treatment to treat, prevent and reduce the severity of this condition. Thai herbal Yahom no.20 (YHF20) is indicated for fatigue and dizziness. The components of YHF20 have been found to have pharmacological effects related to the pathology of chronic cerebral ischemia hypoperfusion. This study aimed to investigate metabolomic changes after YHF20 administration in a rat model of permanent bilateral common carotid artery occlusion (2-VO) induced chronic cerebral ischemia hypoperfusion, and to explore its impact on spatial learning and memory. Albino Wistar rats were randomly allocated to 5 groups; sham, 2-VO, 2-VO+ 100 mg/kg YHF20, 2-VO+300 mg/kg YHF20, and 2-VO+1000 mg/kg YHF20. The rats were administered YHF20 daily by oral gavage for 56 days after 2-VO induction. Plasma was collected weekly for metabolome change analysis using LC-MS/QTof and toxicity study. The rats were evaluated for spatial learning and memory using the Morris water maze. The results showed that 78 known metabolites and 10 tentative pathways altered after chronic cerebral hypoperfusion, although it was not able to determine the effect on memory and learning behaviors of rats. Glutathione and glutathione metabolism might be metabolite-pathway that were the affect after YHF20 administration in cerebral ischemic condition. The 4 known metabolites may be the metabolites from the constituents of YHF20 could be considered and confirmed for quality control purpose. In conclusion, YHF20 administration might contribute to metabolic changes related to cerebral ischemia condition without the effect on spatial learning and memory, including hepatotoxicity and nephrotoxicity after 56 days of treatment. Alterations in the potential metabolites may provide data support for elucidating dementia pathogenesis and selecting pathways for intervention.PMID:38560220 | PMC:PMC10981045 | DOI:10.1016/j.heliyon.2024.e28027