PubMed

Biomedicines. 2023 Dec 13;11(12):3303. doi: 10.3390/biomedicines11123303.ABSTRACTThe objective of this study was to investigate whether the impairment of farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in juvenile pigs with non-alcoholic fatty liver disease (NAFLD) is associated with changes in the composition of the enterohepatic bile acid pool. Eighteen 15-day-old Iberian pigs, pair-housed in pens, were allocated to receive either a control (CON) or high-fructose, high-fat (HFF) diet. Animals were euthanized in week 10, and liver, blood, and distal ileum (DI) samples were collected. HFF-fed pigs developed NAFLD and had decreased FGF19 expression in the DI and lower FGF19 levels in the blood. Compared with the CON, the HFF diet increased the total cholic acid (CA) and the CA to chenodeoxycholic acid (CDCA) ratio in the liver, DI, and blood. CA and CDCA levels in the DI were negatively and positively correlated with ileal FGF19 expression, respectively, and blood levels of FGF19 decreased with an increasing ileal CA to CDCA ratio. Compared with the CON, the HFF diet increased the gene expression of hepatic 12-alpha-hydrolase, which catalyzes the synthesis of CA in the liver. Since CA species are weaker FXR ligands than CDCA, our results suggest that impairment of FXR-FGF19 signaling in NAFLD pigs is associated with a decrease in FXR agonism in the bile acid pool.PMID:38137523 | DOI:10.3390/biomedicines11123303

Biomedicines. 2023 Dec 13;11(12):3295. doi: 10.3390/biomedicines11123295.ABSTRACTAntipsychotics are an important pharmacotherapy option for the treatment of many mental illnesses. Unfortunately, selecting antipsychotics is often a trial-and-error process due to a lack of understanding as to which medications an individual patient will find most effective and best tolerated. Metabolomics, or the study of small molecules in a biosample, is an increasingly used omics platform that has the potential to identify biomarkers for medication efficacy and toxicity. This systematic review was conducted to identify metabolites and metabolomic pathways associated with antipsychotic use in humans. Ultimately, 42 studies were identified for inclusion in this review, with all but three studies being performed in blood sources such as plasma or serum. A total of 14 metabolite classes and 12 lipid classes were assessed across studies. Although the studies were highly heterogeneous in approach and mixed in their findings, increases in phosphatidylcholines, decreases in carboxylic acids, and decreases in acylcarnitines were most consistently noted as perturbed in patients exposed to antipsychotics. Furthermore, for the targeted metabolomic and lipidomic studies, seven metabolites and three lipid species had findings that were replicated. The most consistent finding for targeted studies was an identification of a decrease in aspartate with antipsychotic treatment. Studies varied in depth of detail provided for their study participants and in study design. For example, in some cases, there was a lack of detail on specific antipsychotics used or concomitant medications, and the depth of detail on sample handling and analysis varied widely. The conclusions here demonstrate that there is a large foundation of metabolomic work with antipsychotics that requires more complete reporting so that an objective synthesis such as a meta-analysis can take place. This will then allow for validation and clinical application of the most robust findings to move the field forward. Future studies should be carefully controlled to take advantage of the sensitivity of metabolomics while limiting potential confounders that may result from participant heterogeneity and varied analysis approaches.PMID:38137517 | DOI:10.3390/biomedicines11123295

Biomedicines. 2023 Dec 1;11(12):3201. doi: 10.3390/biomedicines11123201.ABSTRACTAptamers, short strands of either DNA, RNA, or peptides, known for their exceptional specificity and high binding affinity to target molecules, are providing significant advancements in the field of health. When seamlessly integrated into biosensor platforms, aptamers give rise to aptasensors, unlocking a new dimension in point-of-care diagnostics with rapid response times and remarkable versatility. As such, this review aims to present an overview of the distinct advantages conferred by aptamers over traditional antibodies as the molecular recognition element in biosensors. Additionally, it delves into the realm of specific aptamers made for the detection of biomarkers associated with infectious diseases, cancer, cardiovascular diseases, and metabolomic and neurological disorders. The review further elucidates the varying binding assays and transducer techniques that support the development of aptasensors. Ultimately, this review discusses the current state of point-of-care diagnostics facilitated by aptasensors and underscores the immense potential of these technologies in advancing the landscape of healthcare delivery.PMID:38137422 | DOI:10.3390/biomedicines11123201

Foods. 2023 Dec 15;12(24):4493. doi: 10.3390/foods12244493.ABSTRACTSea buckthorn (Hippophae rhamnoides L.) (SB) is increasingly consumed worldwide as a food and food supplement. The remarkable richness in biologically active phytochemicals (polyphenols, carotenoids, sterols, vitamins) is responsible for its purported nutritional and health-promoting effects. Despite the considerable interest and high market demand for SB-based supplements, a limited number of studies report on the authentication of such commercially available products. Herein, untargeted metabolomics based on ultra-high-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UHPLC-QTOF-ESI+MS) were able to compare the phytochemical fingerprint of leaves, berries, and various categories of SB-berry herbal supplements (teas, capsules, tablets, liquids). By untargeted metabolomics, a multivariate discrimination analysis and a univariate approach (t-test and ANOVA) showed some putative authentication biomarkers for berries, e.g., xylitol, violaxanthin, tryptophan, quinic acid, quercetin-3-rutinoside. Significant dominant molecules were found for leaves: luteolin-5-glucoside, arginine, isorhamnetin 3-rutinoside, serotonin, and tocopherol. The univariate analysis showed discriminations between the different classes of food supplements using similar algorithms. Finally, eight molecules were selected and considered significant putative authentication biomarkers. Further studies will be focused on quantitative evaluation.PMID:38137297 | DOI:10.3390/foods12244493

Foods. 2023 Dec 14;12(24):4486. doi: 10.3390/foods12244486.ABSTRACTChina Xihu Longjing tea is famous for its good flavor and quality. However, information on its related metabolites, except for flavonoids, is largely deficient. Different processing methods for China Xihu Longjing tea fixing-by machines at both the first and second step (A1), first step by machine and second step by hand (A2), first step by hand and second step by machine (A3), and by hand at both the first and second step (A4)-were compared using a UHPLC-QE-MS-based metabolomics approach. Liquid chromatography-mass spectrometry was used to analyze the metabolic profiles of the processed samples. A total of 490 metabolites (3 alkaloids, 3 anthracenes, 15 benzene and substituted derivatives, 2 benzopyrans, 13 coumarins and derivatives, 128 flavonoids, 4 furanoid lignans, 16 glycosides and derivatives, 5 indoles and derivatives, 18 isocoumarins and derivatives, 4 chalcones and dihydrochalcones, 4 naphthopyrans, 3 nucleosides, 78 organic acids and derivatives, 55 organooxygen compounds, 5 phenols, 109 prenol lipids, 3 saccharolipids, 3 steroids and steroid derivatives, and 17 tannins) were identified. The different metabolic profiles were distinguished using PCA and OPLS-DA. There were differences in the types and contents of the metabolites, especially flavonoids, furanoid lignans, glycosides and derivatives, organic acids and derivatives, and organooxygen compounds. There was a positive correlation between flavonoid metabolism and amino acid metabolism. However, there was a negative correlation between flavonoid metabolism and amino acid metabolism, which had the same trend as prenol lipid metabolism and tannins. This study provides new valuable information regarding differences in the metabolite profile of China Xihu Longjing tea processed based on machine fixing and on manual fixing methods.PMID:38137290 | DOI:10.3390/foods12244486

Foods. 2023 Dec 14;12(24):4476. doi: 10.3390/foods12244476.ABSTRACTDue to its significant physiological effects, a sulfated polysaccharide has been considered an important nutrient of sea cucumber, but its metabolism in vivo is still unclear. The present study investigated the metabolism of a sea cucumber sulfated polysaccharide (SCSP) in rats and its influence on the metabolite profiles. The quantification by HPLC-MS/MS revealed that the blood level of SCSP achieved a maximum of 54.0 ± 4.8 μg/mL at 2 h after gavage, almost no SCSP was excreted through urine, and 55.4 ± 29.8% of SCSP was eliminated through feces within 24 h. These results prove the utilization of SCSP by gut microbiota, and a further microbiota sequencing analysis indicated that the SCSP utilization in the gut was positively correlated with Muribaculaceae and Clostridia_UCG-014. In addition, the non-targeted metabolomic analysis demonstrated the significant effects of SCSP administration on the metabolite profiles of blood, urine, and feces. It is worth noting that the SCSP supplement decreased palmitic acid, stearic acid, and oleic acid in blood and urine while increasing stearic acid, linoleic acid, and γ-linolenic acid in feces, suggesting the inhibition of fat absorption and the enhancement of fat excretion by SCSP, respectively. The present study shed light on the metabolism in vivo and the influence on the fat metabolism of SCSP.PMID:38137281 | DOI:10.3390/foods12244476

Foods. 2023 Dec 11;12(24):4445. doi: 10.3390/foods12244445.ABSTRACTTomato fruits are rich in flavonoids. This study explores the effect of transcription factor SlNOR-like1 on the accumulation of flavonoids in tomato fruits at different ripening stages. We used ultra-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to analyze wild-type (WT) and NOR-like1 CRISPR/Cas9-edited (NOR-like1) tomato fruits. A total of 50 flavonoid metabolites were accurately identified and determined in tomatoes. The flavonoid metabolic differences were observed among the different tomato sample groups using PCA and OPLS-DA analysis. There were 16 differential flavonoids (13 upregulated and 3 downregulated) identified between WT-GR (WT tomato at the green-ripening stage) and NOR-like1-GR (NOR-like1 tomato at the green-ripening stage), 9 differential flavonoids (six upregulated and three downregulated) identified between WT-BR3 (WT tomato at the color-breaking stage) and NOR-like1-BR3 (NOR-like1 tomato at the color-breaking stage), and 12 differential flavonoids (11 upregulated and 1 downregulated) identified between WT-BR9 (WT tomato at the red-ripening stage) and NOR-like1-BR9 (NOR-like1 tomato at the red-ripening stage). Rutin, nicotiflorin, naringenin chalcone, eriodictyol, and naringenin-7-glucoside were the five flavonoids with the highest content in the ripening stages (BR3 and BR9) in both WT and NOR-like1 tomato fruits. The overall flavonoid contents in WT tomato fruits changed little from GR to BR3 and decreased from BR3 to BR9; meanwhile, in the NOR-like1 tomato fruits, the total amounts of the flavonoids exhibited an increasing trend during all three ripening stages. The accumulation pattern of flavonoid metabolites in NOR-like1 tomato fruits differed from that in WT tomato fruits, especially in the later ripening process of BR9. The transcription factor SlNOR-like1 has an impact on the accumulation of flavonoids in tomato fruits. The results provide a preliminary basis for subsequent research into its regulatory mechanism and will be helpful for attaining future improvements in the nutritional quality and postharvest treatment of tomato fruits.PMID:38137249 | DOI:10.3390/foods12244445

Foods. 2023 Dec 7;12(24):4410. doi: 10.3390/foods12244410.ABSTRACTHuangqin tea (HQT), a Non-Camellia Tea derived from the aerial parts of Scutellaria baicalensis, is widely used in the north of China. The intervention effects of HQT on intestinal inflammation and tumors have been found recently, but the active ingredient and mechanism of action remain unclear. This study aimed to investigate the interactions between the potential flavonoid active components and gut microbiota through culture experiments in vitro combined with HPLC-UV, UPLC-QTOF-MS, and 16S rDNA sequencing technology. The results showed that the HQT total flavonoids were mainly composed of isocarthamidin-7-O-β-D-glucuronide, carthamidin-7-O-β-D-glucuronide, scutellarin, and others, which interact closely with gut microbiota. After 48 h, the primary flavonoid glycosides transformed into corresponding aglycones with varying degrees of deglycosylation. The composition of the intestinal microbiota was changed significantly. The beneficial bacteria, such as Enterococcus and Parabacteroides, were promoted, while the harmful bacteria, such as Shigella, were inhibited. The functional prediction results have indicated notable regulatory effects exerted by total flavonoids and scutellarin on various pathways, including purine metabolism and aminoacyl-tRNA biosynthesis, among others, to play a role in the intervention of inflammation and tumor-related diseases. These findings provided valuable insights for further in-depth research and investigation of the active ingredients, metabolic processes, and mechanisms of HQT.PMID:38137214 | DOI:10.3390/foods12244410

Foods. 2023 Dec 7;12(24):4409. doi: 10.3390/foods12244409.ABSTRACTThe aim of this study was to investigate the antidiabetic effect of the extract from Sargassum pallidum (SPPE) on type 2 diabetes mellitus (T2DM) mice. SPPE treatment alleviated hyperglycemia, insulin resistance (IR), liver and pancreatic tissue damage, hyperlipidemia and hepatic oxidative stress resulting from T2DM. SPPE reversed phosphoenolpyruvate carboxylase (PEPCK) and hexokinase (HK) activities to improve gluconeogenesis and glycogen storage in the liver. Furthermore, SPPE modulated glucose metabolism by regulating the levels of mRNA expression involving the PI3K/Akt/FOXO1/G6pase/GLUT2 pathway and could inhibit fatty acid synthesis by reducing the gene expression levels of fatty acid synthase (FAS) and acetyl-CoA carboxylase-1 (ACC-1). A 16 sRNA analysis indicated that SPPE treatment also reversed gut dysbiosis by increasing the abundance of beneficial bacteria (Bacteroides and Lactobacillus) and suppressing the proliferation of harmful bacteria (Enterococcus and Helicobacter). Untargeted metabolomics results indicated that histidine metabolism, nicotinate and nicotinamide metabolism and fatty acid biosynthesis were significantly influenced by SPPE. Thus, SPPE may be applied as an effective dietary supplement or drug in the management of T2DM.PMID:38137213 | DOI:10.3390/foods12244409

Foods. 2023 Dec 5;12(24):4383. doi: 10.3390/foods12244383.ABSTRACTEggplant is one of the most important vegetable crops worldwide and has been considered to have great antioxidant activity. However, little information is available about the primary metabolic composition of the nutritional values of eggplant. Using a widely targeted metabolome approach, the current study investigated primary metabolic variation in 13 eggplant varieties with different morphologies. A total of 503 primary metabolites (amino acids, lipids, nucleotides, organic acids, vitamin, saccharides, and alcohols) and 170 phenolic acids were detected, among which 211 metabolites were differently accumulated. Metabolic pathway analysis of the differential metabolites revealed the significant enrichment of phenylpropanoid biosynthesis, arginine biosynthesis, alpha-linolenic acid metabolism, and linoleic acid metabolism. The higher levels of amino acids and lipids were related to the umami, soft, and waxy taste of eggplant fruit. The present work substantially contributes to the knowledge of primary metabolite compositions regarding fruit-eating quality and provides useful information for the future breeding of eggplant.PMID:38137187 | DOI:10.3390/foods12244383

Genes (Basel). 2023 Dec 18;14(12):2232. doi: 10.3390/genes14122232.ABSTRACTCoptis chinensis is a perennial herb of the Ranunculaceae family. The isoquinoline alkaloid is the main active component of C. chinensis, mainly exists in its rhizomes and has high clinical application potential. The in vitro synthesis of isoquinoline alkaloids is difficult because their structures are complex; hence, plants are still the main source of them. In this study, two-year and four-year rhizomes of C. chinensis were selected to investigate the effect of growth years on the accumulation of isoquinoline alkaloids. Two-year and four-year C. chinensis were selected for metabolomics detection and transcriptomic analysis. A total of 413 alkaloids were detected by metabolomics analysis, of which 92 were isoquinoline alkaloids. (S)-reticuline was a significantly different accumulated metabolite of the isoquinoline alkaloids biosynthetic pathway in C. chinensis between the two groups. The results of transcriptome analysis showed that a total of 464 differential genes were identified, 36 of which were associated with the isoquinoline alkaloid biosynthesis pathway of C. chinensis. Among them, 18 genes were correlated with the content of important isoquinoline alkaloids. Overall, this study provided a comprehensive metabolomic and transcriptomic analysis of the rapid growth stage of C. chinensis rhizome from the perspective of growth years. It brought new insights into the biosynthetic pathway of isoquinoline alkaloids and provided information for utilizing biotechnology to improve their contents in C. chinensis.PMID:38137054 | DOI:10.3390/genes14122232

Genes (Basel). 2023 Dec 18;14(12):2230. doi: 10.3390/genes14122230.ABSTRACTPuerarin, a class of isoflavonoid compounds concentrated in the roots of Puerarias, has antipyretic, sedative, and coronary blood-flow-increasing properties. Although the biosynthetic pathways of puerarin have been investigated by previous researchers, studies focusing on the influence of different growth stages on the accumulation of metabolites in the puerarin pathway are not detailed, and it is still controversial at the last step of the 8-C-glycosylation reaction. In this study, we conducted a comprehensive analysis of the metabolomic and transcriptomic changes in Pueraria montana var. thomsonii during two growing years, focusing on the vigorous growth and dormant stages, to elucidate the underlying mechanisms governing the changes in metabolite and gene expression within the puerarin biosynthesis pathway. In a comparison of the two growth stages in the two groups, puerarin and daidzin, the main downstream metabolites in the puerarin biosynthesis pathway, were found to accumulate mainly during the vigorous growth stage. We also identified 67 common differentially expressed genes in this pathway based on gene expression differences at different growth stages. Furthermore, we identified four candidate 8-C-GT genes that potentially contribute to the conversion of daidzein into puerarin and eight candidate 7-O-GT genes that may be involved in the conversion of daidzein into daidzin. A co-expression network analysis of important UGTs and HIDs along with daidzein and puerarin was conducted. Overall, our study contributes to the knowledge of puerarin biosynthesis and offers information about the stage at which the 8-C-glycosylation reaction occurs in biosynthesis. These findings provide valuable insights into the cultivation and quality enhancement of Pueraria montana var. thomsonii.PMID:38137052 | DOI:10.3390/genes14122230

Animals (Basel). 2023 Dec 7;13(24):3774. doi: 10.3390/ani13243774.ABSTRACTA total of 30 Simmental crossbred cattle (6.50 months old, 265.0 ± 22.48 kg) were randomly divided into three groups, with 10 heads per group, and fed for 45 days. The diet treatments consisted of the Control group without PFDG supplementation, the PFDG-15% group with 15% PFDG substituting for 15% concentrate, and PFDG-30% group with 30% PFDG substituting for 30% concentrate. The results showed that compared with the Control group, the average daily gain (ADG) of the cattle in the PFDG-30% group decreased significantly (0.890 vs. 0.768 kg/d, p = 0.005). The serum malondialdehyde content of cattle in the PFDG-15% and PFDG-30% groups decreased significantly (p = 0.047) compared to that of the Control group. However, the serum superoxide dismutase activity of cattle in the PFDG-30% group was significantly higher than that of the Control group (p = 0.047). Meanwhile, both the PFDG-15% and PFDG-30% groups (1758.47 vs. 2061.30 μg/mL) showed higher serum levels of immunoglobulin G, while the interleukin-10 concentration was lower in the PFDG-30% group (p = 0.027). In addition, the PFDG-15% and PFDG-30% groups shifted the rumen microbiota by improving the abundances of F082 (related to propionic acid production) and fiber-degrading bacteria (Lachnospiraceae_UGG-009 and Prevotellaceae_UCG-001) and reducing the abundance of the disease-associated bacteria Selenomonas. A Kyoto encyclopedia of genes and genomes (KEGG) analysis illustrated that three key metabolic pathways, including phenylalanine metabolism, pyrimidine metabolism, and tryptophan metabolism, were enriched in the PFDG-15% group, but eight key metabolic pathways, including arachidonic acid metabolism, were enriched in the PFDG-30% group. Importantly, both the PFDG-15% and PFDG-30% groups increased (p < 0.01) the activities of cellulase, lipase, and protease in the rumen. Finally, the different bacterial abundance in the rumen was associated with changes in the ADG, serum antioxidant capacity, immune status, rumen enzyme activity, and metabolites. These results suggest that PFDG alters rumen microbiome abundance, metabolome, and enzyme activity for enhancing serum antioxidant capacity and the immune status, but when the supplemental level reaches 30%, it has a negative effect on ADG and the anti-inflammatory factors in finishing cattle.PMID:38136811 | DOI:10.3390/ani13243774

J Pharm Biomed Anal. 2023 Dec 19;239:115919. doi: 10.1016/j.jpba.2023.115919. Online ahead of print.ABSTRACTTesticular dysfunction is distinguished by a deficiency in testosterone levels, which can be attributed to the occurrence of oxidative stress injury in Leydig cells. The empirical prescription known as Bushen Zhuanggu Tang, developed by a highly experienced traditional Chinese medicine practitioner with six decades of clinical expertize, aligns with the traditional Chinese medicine principle of "kidney governing bone". Researchers have demonstrated that the administration of BSZGT can effectively enhance testosterone production. The objective of this study is to investigate the potential anti-testicular dysfunction effects of BSZGT and elucidate its underlying mechanism in an in vitro setting. Specifically, the impact of oxidative stress induced by H2O2 on the activity and testosterone levels of Leydig cells (TM3) was examined. Furthermore, the utilization of UPLC-QE-Qrbitrap-MS enabled the identification of the involvement of BSZGT in various metabolic pathways, including arginine biosynthesis, amino acyl-tRNA biosynthesis, Alanine, aspartate and glutamine metabolism, and Citrate Cycle, through the modulation of 25 distinct metabolites. Additionally, a network pharmacological analysis was conducted to investigate the pivotal protein targets associated with the therapeutic effects of BSZGT. The findings demonstrate the identification of six key proteins (CYP19A1, CYP1B1, ALOX5, ARG1, XDH, and MPO) that play a significant role in augmenting testicular function through their involvement in the ovarian steroid production pathway. In summary, our study presents a comprehensive research methodology that combines cell metabonomics and network pharmacology to enhance the discovery of new therapeutic agents for TD.PMID:38134707 | DOI:10.1016/j.jpba.2023.115919

Placenta. 2023 Dec 19;145:143-150. doi: 10.1016/j.placenta.2023.12.019. Online ahead of print.ABSTRACTINTRODUCTION: Duplicated genes or paralogs play important roles in the adaptive function of eukaryotic genomes. Animal studies have shown evidence for the functional role of paralogs in pregnancy, but our knowledge about the role of paralogs in the fetoplacental regulation remains limited. In particular, if fetoplacental metabolic regulation is modulated by differential expression of paralogs remains unexamined.METHODS: In this study, gene expression profiles of day-15 placenta and fetal brain were compared to identify families or groups of paralogous genes expressed in the placenta and brain of male versus female fetuses in mice. A Bayesian modeling was applied to infer directional relationship of transcriptional variation of the paralogs relative to the phylogenetic variation of the genes in each family. Gas chromatography-mass spectrometry (GC-MS) was used to perform untargeted metabolomics analysis of day-15 placenta and fetal brain of both sexes.RESULTS: We identified paralog groups that were expressed in a sex and/or tissue biased manner between the placenta and fetal brain. Bayesian modeling showed evidence for directional relationship between expression and phylogeny of specific paralogs. These relationships were sex specific. GC-MS analysis identified metabolites that were expressed in a sex-bias manner between the placenta and fetal brain. By performing integrative analysis of the metabolomics and gene expression data, we showed that specific groups of metabolites and paralogous genes were expressed in a coordinated manner between the placenta and fetal brain.DISCUSSION: The findings of this study collectively suggest that paralogs play an influential role in the regulation of the brain-placental axis in mice.PMID:38134547 | DOI:10.1016/j.placenta.2023.12.019

Anal Chem. 2023 Dec 22. doi: 10.1021/acs.analchem.3c03482. Online ahead of print.ABSTRACTMALDI mass spectrometry imaging has gained major interest in the field of chemical imaging. This technique makes it possible to locate tens to hundreds of ionic signals on the sample surface without any a priori. One of the current challenges is still the limited ability to annotate signals in order to convert m/z values into probable chemical structures. At the same time, data obtained by LC-MS/MS have benefited from the development of numerous chemoinformatics tools, in particular molecular networks, for their efficient annotation. For the first time, we present here the combination of MALDI-FT-ICR imaging with molecular networks from MALDI-MS/MS data directly acquired on plant tissue sections. Annotation improvements are demonstrated, paving the way for new annotation pipelines for MALDI imaging.PMID:38134413 | DOI:10.1021/acs.analchem.3c03482

Chem Res Toxicol. 2023 Dec 22. doi: 10.1021/acs.chemrestox.3c00154. Online ahead of print.ABSTRACTSilver nanoparticles (AgNPs) have been widely utilized in various biomedical and antimicrobial technologies, displaying broad-spectrum activities against Gram-negative and Gram-positive bacteria including multidrug-resistant strains. However, the emergence of resistance to AgNPs upon repeated exposure and the survival of bacteria after initial exposure to antimicrobial agents pose a threat, as they may lead to the development of new resistant populations. To combat the early stages of antibacterial resistance, systematic analysis is essential to understand the immediate response of bacteria to antimicrobial agents. In this study, green-synthesized AgNPs with a diameter of approximately 14 nm were exposed toPseudomonas aeruginosaat three different inhibitory concentrations and at two different time intervals (1 and 4 h) to investigate the perturbations in the metabolome using liquid chromatography-high-resolution mass spectrometry. MetaboAnalyst 5.0 was employed for univariate and multivariate analysis, and the affected metabolic pathways were constructed using a variable important in projection scores above 1 from PLS-DA. The study revealed significant alterations in metabolites associated with cell wall synthesis, energy metabolism, nucleotide metabolism, the TCA cycle, and anaplerotic intermediates of the TCA cycle. Our investigation aimed to comprehensively understand the effects of green-synthesized AgNPs onP. aeruginosa metabolism, providing a more precise snapshot of the bacterium's physiological state through metabolomics approach.PMID:38133952 | DOI:10.1021/acs.chemrestox.3c00154

Toxics. 2023 Dec 12;11(12):1014. doi: 10.3390/toxics11121014.ABSTRACTA growing body of literature has attempted to characterize how traffic-related air pollution (TRAP) affects molecular and subclinical biological processes in ways that could lead to cardiorespiratory disease. To provide a streamlined synthesis of what is known about the multiple mechanisms through which TRAP could lead to cardiorespiratory pathology, we conducted a systematic review of the epidemiological literature relating TRAP exposure to methylomic, proteomic, and metabolomic biomarkers in adult populations. Using the 139 papers that met our inclusion criteria, we identified the omic biomarkers significantly associated with short- or long-term TRAP and used these biomarkers to conduct pathway and network analyses. We considered the evidence for TRAP-related associations with biological pathways involving lipid metabolism, cellular energy production, amino acid metabolism, inflammation and immunity, coagulation, endothelial function, and oxidative stress. Our analysis suggests that an integrated multi-omics approach may provide critical new insights into the ways TRAP could lead to adverse clinical outcomes. We advocate for efforts to build a more unified approach for characterizing the dynamic and complex biological processes linking TRAP exposure and subclinical and clinical disease and highlight contemporary challenges and opportunities associated with such efforts.PMID:38133415 | DOI:10.3390/toxics11121014

Toxics. 2023 Dec 4;11(12):984. doi: 10.3390/toxics11120984.ABSTRACTArecoline is a pyridine alkaloid derived from areca nut in the Arecaceae family. It has extensive medicinal activity, such as analgesic, anti-inflammatory, and anti-allergic. However, the toxicity of Arecoline limits its application. Most current studies on its toxicity mainly focus on immunotoxicity, carcinogenesis, and cancer promotion. However, there are few systematic studies on its hepatotoxicity and mechanisms. Therefore, this research explored the mechanism of hepatotoxicity induced by Arecoline in rats and analyzed endogenous metabolite changes in rat plasma by combining network toxicology with metabolomics. The differential metabolites after Arecoline exposure, such as D-Lysine, N4-Acetylaminobutanal, and L-Arginine, were obtained by metabolomics study, and these differential metabolites were involved in the regulation of lipid metabolism, amino acid metabolism, and vitamin metabolism. Based on the strategy of network toxicology, Arecoline can affect the HIF-1 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, and other concerning pathways by regulating critical targets, such as ALB, CASP3, EGFR, and MMP9. Integration of metabolomics and network toxicology results were further analyzed, and it was concluded that Arecoline may induce hepatotoxicity by mediating oxidative stress, inflammatory response, energy and lipid metabolism, and cell apoptosis.PMID:38133385 | DOI:10.3390/toxics11120984

Mar Drugs. 2023 Dec 18;21(12):646. doi: 10.3390/md21120646.ABSTRACTThe secondary metabolites of marine fungi with rich chemical diversity and biological activity are an important and exciting target for natural product research. This study aimed to investigate the fungal community in Quanzhou Bay, Fujian, and identified 28 strains of marine fungi. A total of 28 strains of marine fungi were screened for small-scale fermentation by the OSMAC (One Strain-Many Compounds) strategy, and 77 EtOAc crude extracts were obtained and assayed for cancer cell inhibition rate. A total of six strains of marine fungi (P-WZ-2, P-WZ-3-2, P-WZ-4, P-WZ-5, P56, and P341) with significant changes in cancer cell inhibition induced by the OSMAC strategy were analysed by UPLC-QTOF-MS. The ACD/MS Structure ID Suite software was used to predict the possible structures with inhibitory effects on cancer cells. A total of 23 compounds were identified, of which 10 compounds have been reported to have potential anticancer activity or cytotoxicity. In this study, the OSMAC strategy was combined with an untargeted metabolomics approach based on UPLC-QTOF-MS to efficiently analyse the effect of changes in culture conditions on anticancer potentials and to rapidly find active substances that inhibit cancer cell growth.PMID:38132967 | DOI:10.3390/md21120646