PubMed

Small Methods. 2023 Nov 3:e2301192. doi: 10.1002/smtd.202301192. Online ahead of print.ABSTRACTIn vitro diagnosis (IVD) is pivotal in modern medicine, enabling early disease detection and treatment optimization. Omics technologies, particularly proteomics and metabolomics, offer profound insights into IVD. Despite its significance, omics analyses for IVD face challenges, including low analyte concentrations and the complexity of biological environments. In addition, the direct omics analysis by mass spectrometry (MS) is often hampered by issues like large sample volume requirements and poor ionization efficiency. Through manipulating their size, surface charge, and functionalization, as well as the nanoparticle-fluid incubation conditions, nanomaterials have emerged as a promising solution to extract biomolecules and enhance the desorption/ionization efficiency in MS detection. This review delves into the last five years of nanomaterial applications in omics, focusing on their role in the enrichment, separation, and ionization analysis of proteins and metabolites for IVD. It aims to provide a comprehensive update on nanomaterial design and application in omics, highlighting their potential to revolutionize IVD.PMID:37922520 | DOI:10.1002/smtd.202301192

Adv Healthc Mater. 2023 Nov 3:e2302128. doi: 10.1002/adhm.202302128. Online ahead of print.ABSTRACTPeripheral nerve injuries (PNI) can lead to mitochondrial dysfunction and energy depletion within the affected microenvironment. Our objective was to investigate the potential of transplanting mitochondria to reshape the neural regeneration microenvironment. High-purity functional mitochondria with an intact structure were extracted from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) using the Dounce homogenization combined with ultracentrifugation. Results showed that when hUCMSC-derived mitochondria (hUCMSC-Mitos) were co-cultured with Schwann cells (SCs), they promoted the proliferation, migration, and respiratory capacity of SCs. Acellular nerve allografts (ANAs) have shown promise in nerve regeneration, however, their therapeutic effect is not satisfactory enough. The incorporation of hUCMSC-Mitos within ANAs (referred to as Mito-ANAs) has the potential to remodel the regenerative microenvironment. This approach demonstrated satisfactory outcomes in terms of tissue regeneration and functional recovery. Particularly, we propose for the first time the use of metabolomics and bioenergetic profiling to analyze the energy metabolism microenvironment after PNI. This remodeling occurs through the enhancement of the tricarboxylic acid (TCA) cycle and the regulation of associated metabolites, resulting in increased energy synthesis. Overall, the hUCMSC-Mito-loaded ANAs exhibited high functionality to promote nerve regeneration, providing a novel regenerative strategy based on improving energy metabolism for neural repair. This article is protected by copyright. All rights reserved.PMID:37922434 | DOI:10.1002/adhm.202302128

Arch Toxicol. 2023 Nov 3. doi: 10.1007/s00204-023-03622-0. Online ahead of print.ABSTRACTGlyphosate is a widely used active ingredient in agricultural herbicides, inhibiting the biosynthesis of aromatic amino acids in plants by targeting their shikimate pathway. Our gut microbiota also facilitates the shikimate pathway, making it a vulnerable target when encountering glyphosate. Dysbiosis in the gut microbiota may impair the gut-brain axis, bringing neurological outcomes. To evaluate the neurotoxicity and biochemical changes attributed to glyphosate, we exposed mice with the reference dose (RfD) set by the U.S. EPA (1.75 mg/Kg-BW/day) and its hundred-time-equivalence (175 mg/Kg-BW/day) chronically via drinking water, then compared a series of neurobehaviors and their fecal/serum metabolomic profile against the non-exposed vehicles (n = 10/dosing group). There was little alteration in the neurobehavior, including motor activities, social approach, and conditioned fear, under glyphosate exposure. Metabolomic differences attributed to glyphosate were observed in the feces, corresponding to 68 and 29 identified metabolites with dysregulation in the higher and lower dose groups, respectively, compared to the vehicle-control. There were less alterations observed in the serum metabolome. Under 175 mg/Kg-BW/day of glyphosate exposure, the aromatic amino acids (phenylalanine, tryptophan, and tyrosine) were reduced in the feces but not in the serum of mice. We further focused on how tryptophan metabolism was dysregulated based on the pathway analysis, and identified the indole-derivatives were more altered compared to the serotonin and kynurenine derivatives. Together, we obtained a three-dimensional data set that records neurobehavioral, fecal metabolic, and serum biomolecular dynamics caused by glyphosate exposure at two different doses. Our data showed that even under the high dose of glyphosate irrelevant to human exposure, there were little evidence that supported the impairment of the gut-brain axis.PMID:37922104 | DOI:10.1007/s00204-023-03622-0

Vet Q. 2023 Nov 3:1-41. doi: 10.1080/01652176.2023.2280041. Online ahead of print.ABSTRACTEpigallocatechin gallate (EGCG) is a main component in green tea extract, which possesses multiple bioactivities. The present research studied the effects of EGCG on the laying performance, egg quality, immune status, antioxidant capacity, and hepatic metabolome of Linwu laying ducks reared under high temperature. A total of 180 42-w-old healthy Linwu laying ducks were allocated into control or EGCG-treated groups. Each treatment had 6 replicates with 15 ducks in each replicate. Diets for the two groups were basal diets supplemented with 0 or 300 mg/kg EGCG, respectively. All ducks were raised in the high temperature condition (35 ± 2 °C for 6 h from 10:00 to 16:00, and 28 ± 2 °C for the other 18 h from 16:00 to 10:00 the next day) for 21 days. Results showed that EGCG increased the egg production rate (P = 0.014). and enhanced the immunocompetence by improving serum levels of immunoglobulin A (P = 0.008) and immunoglobulin G (P = 0.006). EGCG also fortified the antioxidant capacity by activating superoxide dismutase (P = 0.012), catalase (P = 0.009), and glutathione peroxidase (P = 0.021), and increasing the level of heat-shock protein 70 (P = 0.003) in laying ducks' liver. At the same time, hepatic metabolomics result suggested that EGCG increased the concentration of several key metabolites, such as spermidine (P = 0.031), tetramethylenediamine (P = 0.009), hyoscyamine (P = 0.026), β-nicotinamide adenine dinucleotide phosphate (P = 0.038), and pantothenic acid (P = 0.010), which were involved in the metabolic pathways of glutathione metabolism, arginine and proline metabolism, β-alanine metabolism, and tropane, piperidine and pyridine alkaloid biosynthesis. In conclusion, 300 mg/kg dietary EGCG showed protection effects on the laying ducks reared in high temperature by improving the immune and antioxidant capacities, which contributed to the increase of laying performance of ducks. The potential mechanism could be that EGCG modulate the synthesis of key metabolites and associated metabolic pathways.PMID:37921498 | DOI:10.1080/01652176.2023.2280041

Microbiol Spectr. 2023 Nov 3:e0274323. doi: 10.1128/spectrum.02743-23. Online ahead of print.ABSTRACTPlants of the genus Otoba have been the basis for the treatment of tropical diseases in indigenous communities of countries like Colombia. Despite the lack of knowledge about their bioactive principles, endophytic fungi derived from medicinal plants are a prolific source of innovative chemistry. We systematically investigated the secondary metabolite production of a previously undescribed species of Diaporthe, herein introduced as Diaporthe caliensis sp. nov., using different metabolomics approaches together with classical chemical screening. To get an outline of the chemical space produced by this fungus, an exploratory molecular networking (MN) analysis was undertaken. A major molecular family was found to contain the known 10-membered lactone phomol (1), together with other putative congeners as compound 3. After isolation by preparative high-performance liquid chromatography, we confirmed phomol (1) as the main reason for the antimicrobial activity of the crude extract. The unknown absolute configuration of 1 was determined by the synthesis of α-methoxy-α-trifluoromethylphenylacetyl (MTPA)-esters and chemical degradation experiments. Moreover, caliensolides A (2) and B (3) were isolated, and their structures were elucidated as novel butenolides structurally unrelated to 1. Overall, the initial MN analysis incorrectly clustered compounds 1 and 3 within a single molecular family, despite evident differences in chemical structures and biosynthetic origin. Contrariwise, the unsupervised substructure discovery algorithm MS2LDA provided a deeper understanding of the fragmentation patterns and correctly clustered the polyketide-lactones produced by D. caliensis sp. nov. Our findings encourage the exploration of Colombian fungal diversity, which as demonstrated here could result in the discovery of new natural products.IMPORTANCEThe integration of metabolomics-based approaches into the discovery pipeline has enabled improved mining and prioritization of prolific secondary metabolite producers such as endophytic fungi. However, relying on automated untargeted analysis tools might lead to misestimation of the chemical complexity harbored in these organisms. Our study emphasizes the importance of isolation and structure elucidation of the respective metabolites in addition to deep metabolome analysis for the correct interpretation of untargeted metabolomics approaches such as molecular networking. Additionally, it encourages the further exploration of endophytic fungi from traditional medicinal plants for the discovery of natural products.PMID:37921483 | DOI:10.1128/spectrum.02743-23

Clin Sci (Lond). 2023 Nov 3:CS20230704. doi: 10.1042/CS20230704. Online ahead of print.ABSTRACTSepsis is known to cause damage to the intestinal mucosa, leading to bacterial translocation, and exacerbation of both local and remote organ impairments. In this study, fecal samples were collected from both septic and healthy individuals. Analysis through 16s rRNA sequencing of the fecal microbiota revealed that sepsis disrupts the balance of the gut microbial community. Recent research has highlighted the association of lipid metabolism with disease. By analyzing the fecal metabolome, four lipid metabolites that showed significant differences between the two groups were identified: PE(O-16:0/0:0), PE(17:0/0:0), PE(0:0/14:0), and PE(12:0/20:5(5Z, 8Z, 11Z, 14Z, 17Z)). Notably, the serum levels of PE(0:0/14:0) were higher in the healthy group. Subsequent in vitro and in vivo experiments demonstrated the protective effects of this compound against sepsis-induced intestinal barrier damage. Label-free proteomic analysis showed significant differences in the expression levels of the aryl hydrocarbon receptor (AHR), a protein implicated in sepsis pathogenesis, between the LPS-Caco-2 and LPS-Caco-2 + PE(0:0/14:0) groups. Further analysis, with the help of Discovery Studio 3.5 software and co-immunoprecipitation assays, confirmed the direct interaction between AHR and PE(0:0/14:0). In the cecal ligation and puncture (CLP) model, treatment with PE(0:0 /14:0) was found to upregulate the expression of tight junction proteins through the AhR/Cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) pathway. This highlights the potential therapeutic use of PE(0:0/14:0) in addressing sepsis-induced intestinal barrier damage.PMID:37921121 | DOI:10.1042/CS20230704

Mol Med Rep. 2023 Dec;28(6):232. doi: 10.3892/mmr.2023.13119. Epub 2023 Nov 3.ABSTRACTTelomeres are major contributors to cell fate and aging through their involvement in cell cycle arrest and senescence. The accelerated attrition of telomeres is associated with aging‑related diseases, and agents able to maintain telomere length (TL) through telomerase activation may serve as potential treatment strategies. The aim of the present study was to assess the potency of a novel telomerase activator on TL and telomerase activity in vivo. The administration of a nutraceutical formulation containing Centella asiatica extract, vitamin C, zinc and vitamin D3 in 18‑month‑old rats for a period of 3 months reduced the telomere shortening rate at the lower supplement dose and increased mean the TL at the higher dose, compared to pre‑treatment levels. TL was determined using the Q‑FISH method in peripheral blood mononuclear cells collected from the tail vein of the rats and cultured with RPMI‑1640 medium. In both cases, TLs were significantly longer compared to the untreated controls (P≤0.001). In addition, telomerase activity was increased in the peripheral blood mononuclear cells of both treatment groups. On the whole, the present study demonstrates that the nutraceutical formulation can maintain or even increase TL and telomerase activity in middle‑aged rats, indicating a potential role of this formula in the prevention and treatment of aging‑related diseases.PMID:37921058 | DOI:10.3892/mmr.2023.13119

Cancer Commun (Lond). 2023 Nov 2. doi: 10.1002/cac2.12502. Online ahead of print.ABSTRACTBACKGROUND: Metabolism reprogramming plays a vital role in glioblastoma (GBM) progression and recurrence by producing enough energy for highly proliferating tumor cells. In addition, metabolic reprogramming is crucial for tumor growth and immune-escape mechanisms. Epidermal growth factor receptor (EGFR) amplification and EGFR-vIII mutation are often detected in GBM cells, contributing to the malignant behavior. This study aimed to investigate the functional role of the EGFR pathway on fatty acid metabolism remodeling and energy generation.METHODS: Clinical GBM specimens were selected for single-cell RNA sequencing and untargeted metabolomics analysis. A metabolism-associated RTK-fatty acid-gene signature was constructed and verified. MK-2206 and MK-803 were utilized to block the RTK pathway and mevalonate pathway induced abnormal metabolism. Energy metabolism in GBM with activated EGFR pathway was monitored. The antitumor effect of Osimertinib and Atorvastatin assisted by temozolomide (TMZ) was analyzed by an intracranial tumor model in vivo.RESULTS: GBM with high EGFR expression had characteristics of lipid remodeling and maintaining high cholesterol levels, supported by the single-cell RNA sequencing and metabolomics of clinical GBM samples. Inhibition of the EGFR/AKT and mevalonate pathways could remodel energy metabolism by repressing the tricarboxylic acid cycle and modulating ATP production. Mechanistically, the EGFR/AKT pathway upregulated the expressions of acyl-CoA synthetase short-chain family member 3 (ACSS3), acyl-CoA synthetase long-chain family member 3 (ACSL3), and long-chain fatty acid elongation-related gene ELOVL fatty acid elongase 2 (ELOVL2) in an NF-κB-dependent manner. Moreover, inhibition of the mevalonate pathway reduced the EGFR level on the cell membranes, thereby affecting the signal transduction of the EGFR/AKT pathway. Therefore, targeting the EGFR/AKT and mevalonate pathways enhanced the antitumor effect of TMZ in GBM cells and animal models.CONCLUSIONS: Our findings not only uncovered the mechanism of metabolic reprogramming in EGFR-activated GBM but also provided a combinatorial therapeutic strategy for clinical GBM management.PMID:37920878 | DOI:10.1002/cac2.12502

Comput Struct Biotechnol J. 2023 Oct 19;21:5136-5143. doi: 10.1016/j.csbj.2023.10.033. eCollection 2023.ABSTRACTPURPOSE: Meta-analyses failed to accurately identify patients with non-metastatic breast cancer who are likely to benefit from chemotherapy, and metabolomics could provide new answers. In our previous published work, patients were clustered using five different unsupervised machine learning (ML) methods resulting in the identification of three clusters with distinct clinical and simulated survival data. The objective of this study was to evaluate the survival outcomes, with extended follow-up, using the same 5 different methods of unsupervised machine learning.EXPERIMENTAL DESIGN: Forty-nine patients, diagnosed between 2013 and 2016, with non-metastatic BC were included retrospectively. Median follow-up was extended to 85.8 months. 449 metabolites were extracted from tumor resection samples by combined Liquid chromatography-mass spectrometry (LC-MS). Survival analyses were reported grouping together Cluster 1 and 2 versus cluster 3. Bootstrap optimization was applied.RESULTS: PCA k-means, K-sparse and Spectral clustering were the most effective methods to predict 2-year progression-free survival with bootstrap optimization (PFSb); as bootstrap example, with PCA k-means method, PFSb were 94% for cluster 1&2 versus 82% for cluster 3 (p = 0.01). PCA k-means method performed best, with higher reproducibility (mean HR=2 (95%CI [1.4-2.7]); probability of p ≤ 0.05 85%). Cancer-specific survival (CSS) and overall survival (OS) analyses highlighted a discrepancy between the 5 ML unsupervised methods.CONCLUSION: Our study is a proof-of-principle that it is possible to use unsupervised ML methods on metabolomic data to predict PFS survival outcomes, with the best performance for PCA k-means. A larger population study is needed to draw conclusions from CSS and OS analyses.PMID:37920813 | PMC:PMC10618114 | DOI:10.1016/j.csbj.2023.10.033

Can J Kidney Health Dis. 2023 Oct 30;10:20543581231209012. doi: 10.1177/20543581231209012. eCollection 2023.ABSTRACTPURPOSE OF REVIEW: Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease (CKD) for which many treatments exist that have been shown to prevent CKD progression and kidney failure. However, DKD is a complex and heterogeneous etiology of CKD with a spectrum of phenotypes and disease trajectories. In this narrative review, we discuss precision medicine approaches to DKD, including genomics, metabolomics, proteomics, and their potential role in the management of diabetes mellitus and DKD. A patient and caregivers of patients with lived experience with CKD were involved in this review.SOURCES OF INFORMATION: Original research articles were identified from MEDLINE and Google Scholar using the search terms "diabetes," "diabetic kidney disease," "diabetic nephropathy," "chronic kidney disease," "kidney failure," "dialysis," "nephrology," "genomics," "metabolomics," and "proteomics."METHODS: A focused review and critical appraisal of existing literature regarding the precision medicine approaches to the diagnosis, prognosis, and treatment of diabetes and DKD framed by a patient partner's/caregiver's lived experience.KEY FINDINGS: Distinguishing diabetic nephropathy from CKD due to other types of DKD and non-DKD is challenging and typically requires a kidney biopsy for a diagnosis. Biomarkers have been identified to assist with the prediction of the onset and progression of DKD, but they have yet to be incorporated and evaluated relative to clinical standard of care CKD and kidney failure risk prediction tools. Genomics has identified multiple causal genetic variants for neonatal diabetes mellitus and monogenic diabetes of the young that can be used for diagnostic purposes and to specify antiglycemic therapy. Genome-wide-associated studies have identified genes implicated in DKD pathophysiology in the setting of type 1 and 2 diabetes but their translational benefits are lagging beyond polygenetic risk scores. Metabolomics and proteomics have been shown to improve diagnostic accuracy in DKD, have been used to identify novel pathways involved in DKD pathogenesis, and can be used to improve the prediction of CKD progression and kidney failure as well as predict response to DKD therapy.LIMITATIONS: There are a limited number of large, high-quality prospective observational studies and no randomized controlled trials that support the use of precision medicine based approaches to improve clinical outcomes in adults with or at risk of diabetes and DKD. It is unclear which patients may benefit from the clinical use of genomics, metabolomics and proteomics along the spectrum of DKD trajectory.IMPLICATIONS: Additional research is needed to evaluate the role of the use of precision medicine for DKD management, including diagnosis, differentiation of diabetic nephropathy from other etiologies of DKD and CKD, short-term and long-term risk prognostication kidney outcomes, and the prediction of response to and safety of disease-modifying therapies.PMID:37920777 | PMC:PMC10619345 | DOI:10.1177/20543581231209012

Front Plant Sci. 2023 Oct 18;14:1259561. doi: 10.3389/fpls.2023.1259561. eCollection 2023.ABSTRACTThe type and content of carbohydrates in konjac corms are an essential factors in determining the quality of konjac; however, the pattern of carbohydrate changes and the mechanism regulating the development of mother and daughter corms in the "relay growth" process of Amorphophallus muelleri remain unclear. This study aimed to investigate changes in corm carbohydrates during the growth cycle of A. muelleri and to compare the carbohydrate composition and the expression of related genes between mother and daughter corms. Integrated metabolome and RNA-seq analyses identified 37 differential metabolites as well as 8074 genes that were differentially expressed between mother and daughter corms, the majority of which were involved in starch and sucrose metabolism. More than 80% of the differential metabolites, including sucrose and starch, tended to accumulate in the mother corms; however, konjac glucomannan (KGM), as one of the most important carbohydrates and its major component of the corm, accumulated in higher amounts in the daughter corms. In addition, the expression of invertase and alpha-amylase that promote the breakdown of sucrose and starch was 351.78- and 15.63-fold higher, respectively, in the daughter corm, whereas that of the starch synthesis gene AkWAXY was only 0.096 times as high as in the mother corms. Furthermore, the level of cellulose synthase-like protein G, which promotes KGM synthesis, was 3.85 times higher in daughter corms compared to mother corms. Thus, we inferred that the daughter and mother corms had two distinct carbohydrate utilization strategies. This study provides insights into temporal changes in carbohydrates during the growth cycle of A. muelleri.PMID:37920719 | PMC:PMC10619727 | DOI:10.3389/fpls.2023.1259561

Front Med (Lausanne). 2023 Oct 18;10:1247851. doi: 10.3389/fmed.2023.1247851. eCollection 2023.ABSTRACTAshitaba seems to improve glucose intolerance and decrease triglyceride (TG) and total cholesterol (TC), which contribute to the development of non-alcoholic fatty liver disease (NAFLD). However, it remains to be explored the mechanism of Ashitaba in managing NAFLD. We determined the impact of Ashitaba on NAFLD, particularly its underlying mechanisms at the bioinformatic level. The established NAFLD mouse model was treated with or without Ashitaba, and the underlying mechanism was explored using transcriptomics paired with metabolomics. Ashitaba reduced obesity and liver steatosis in NAFLD mice. It identified 429 differentially expressed genes (DEGs) and verified 45 differential metabolites, especially those that alleviate NAFLD via the FXR signaling pathway. Our data may provide insight into the therapeutic impact of Ashitaba in the management of NAFLD and may be useful in clinical interventions for NAFLD.PMID:37920601 | PMC:PMC10618682 | DOI:10.3389/fmed.2023.1247851

PNAS Nexus. 2023 Oct 31;2(10):pgad326. doi: 10.1093/pnasnexus/pgad326. eCollection 2023 Oct.ABSTRACTPlants produce specialized metabolites with defensive properties that are often synthesized through the coordinated regulation of metabolic genes by transcription factors in various biological contexts. In this study, we investigated the regulatory function of the transcription factor PhERF1 from petunia (Petunia hybrida), which belongs to a small group of ETHYLENE RESPONSE FACTOR (ERF) family members that regulate the biosynthesis of bioactive alkaloids and terpenoids in various plant lineages. We examined the effects of transiently overexpressing PhERF1 in petunia leaves on the transcriptome and metabolome, demonstrating the production of a class of specialized steroids, petuniolides, and petuniasterones in these leaves. We also observed the activation of many metabolic genes, including those involved in sterol biosynthesis, as well as clustered genes that encode new metabolic enzymes, such as cytochrome P450 oxidoreductases, 2-oxoglutarate-dependent dioxygenases, and BAHD acyltransferases. Furthermore, we determined that PhERF1 transcriptionally induces downstream metabolic genes by recognizing specific cis-regulatory elements in their promoters. This study highlights the potential of evolutionarily conserved transcriptional regulators to induce the production of specialized products through transcriptional reprogramming.PMID:37920550 | PMC:PMC10619512 | DOI:10.1093/pnasnexus/pgad326

Heliyon. 2023 Oct 21;9(11):e21392. doi: 10.1016/j.heliyon.2023.e21392. eCollection 2023 Nov.ABSTRACTImproved biosynthesis of commercially and pharmacologically relevant phytometabolites through genetic and metabolic engineering is a lucrative strategy for crop improvement. However, identifying appropriate biosynthetic pathways pertaining to specific bioactivities has been challenging since the major metabolic pathways remain closely interconnected. Here we propose a reverse association strategy in which, based on the phytochemical profile, putative target metabolic pathways could be identified for increased production of phytochemicals. Dried seed fruits of Coriandrum sativum, Trachyspermum ammi, Cuminum cyminum, and Foeniculum vulgare (family Apiaceae) were subjected to untargeted gas chromatography-mass spectrometry-based phytochemical profiling followed by evaluation of the overall antioxidant profile using multiple antioxidant assays. Using bioinformatics approaches, specific phytochemical classes and the enrichment of their respective biosynthetic pathways were identified. Collectively, the data suggest enrichment of isoprenoids and fatty acids biosynthetic pathways. The close association of metabolic pathways with antioxidant capacities indicated a need for enrichment of specific yet closely-related metabolic pathways to achieve an improved quality of spices for better antioxidant effects.PMID:37920519 | PMC:PMC10618831 | DOI:10.1016/j.heliyon.2023.e21392

Heliyon. 2023 Oct 19;9(11):e21011. doi: 10.1016/j.heliyon.2023.e21011. eCollection 2023 Nov.ABSTRACTAging is associated with gradual changes in liver structure, altered metabolites and other physiological/pathological functions in hepatic cells. However, its characterized phenotypes based on altered metabolites and the underlying biological mechanism are unclear. Advancements in high-throughput omics technology provide new opportunities to understand the pathological process of aging. Here, in our present study, both metabolomics and phosphoproteomics were applied to identify the altered metabolites and phosphorylated proteins in liver of young (the WTY group) and naturally aged (the WTA group) mice, to find novel biomarkers and pathways, and uncover the biological mechanism. Analysis showed that the body weights, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased in the WTA group. The grips decreased with age, while the triglyceride (TG) and cholesterol (TC) did not change significantly. The increase of fibrosis, accumulation of inflammatory cells, hepatocytes degeneration, the deposition of lipid droplets and glycogen, the damaged mitochondria, and deduction of endoplasmic reticulum were observed in the aging liver under optical and electron microscopes. In addition, a network of metabolites and phosphorylated proteomes of the aging liver was established. Metabolomics detected 970 metabolites in the positive ion mode and 778 metabolites in the negative ion mode. A total of 150 pathways were pooled. Phosphoproteomics identified 2618 proteins which contained 16621 phosphosites. A total of 164 pathways were detected. 65 common pathways were detected in two omics. Phosphorylated protein heat shock protein HSP 90-alpha (HSP90A) and v-raf murine viral oncogene homolog B1(BRAF), related to cancer pathway, were significantly upregulated in aged mice liver. Western blot verified that protein expression of MEK and ERK, downstream of BRAF pathway were elevated in the liver of aging mice. However, the protein expression of BRAF was not a significant difference. Overall, these findings revealed a close link between aging and cancer and contributed to our understanding of the multi-omics changes in natural aging.PMID:37920504 | PMC:PMC10618800 | DOI:10.1016/j.heliyon.2023.e21011

Food Chem X. 2023 Oct 21;20:100952. doi: 10.1016/j.fochx.2023.100952. eCollection 2023 Dec 30.ABSTRACTTo interpret the formation characteristic flavor during oolong tea manufacturing process, the dynamic changes of key flavor components in samples from various processing steps of Tieguanyin oolong tea production were investigated using widely-targeted metabolomic and the transcriptomic approaches. As a result, a total of 1078 metabolites were determined, of which 62 compounds were identified as biomarkers significantly changed over the manufacturing process. Quantitative determination of the total 50,343 transcripts showed 7480 of them were co-expressed different genes. Glutamic acid served as a critical metabolism hub and a signaling molecule for diverse stress responses. Additionally, the targeted quantification results showed that the contents of catechins and xanthine alkaloids in dried tea were dramatically decreased by 20.19% and 7.15% respectively than those in fresh leaves, which potentially contributed to the alleviation of astringent or bitter palates, promoting the characteristic mellow and rich flavor of Tieguanyin oolong tea.PMID:37920364 | PMC:PMC10618703 | DOI:10.1016/j.fochx.2023.100952

Front Microbiol. 2023 Oct 18;14:1286661. doi: 10.3389/fmicb.2023.1286661. eCollection 2023.ABSTRACTBACKGROUND: The use of omics data for monitoring the microbial flow of fresh meat products along a production line and the development of spoilage prediction tools from these data is a promising but challenging task. In this context, we produced a large multivariate dataset (over 600 samples) obtained on the production lines of two similar types of fresh meat products (poultry and raw pork sausages). We describe a full analysis of this dataset in order to decipher how the spoilage microbial ecology of these two similar products may be shaped differently depending on production parameter characteristics.METHODS: Our strategy involved a holistic approach to integrate unsupervised and supervised statistical methods on multivariate data (OTU-based microbial diversity; metabolomic data of volatile organic compounds; sensory measurements; growth parameters), and a specific selection of potential uncontrolled (initial microbiota composition) or controlled (packaging type; lactate concentration) drivers.RESULTS: Our results demonstrate that the initial microbiota, which is shown to be very different between poultry and pork sausages, has a major impact on the spoilage scenarios and on the effect that a downstream parameter such as packaging type has on the overall evolution of the microbial community. Depending on the process, we also show that specific actions on the pork meat (such as deboning and defatting) elicit specific food spoilers such as Dellaglioa algida, which becomes dominant during storage. Finally, ecological network reconstruction allowed us to map six different metabolic pathways involved in the production of volatile organic compounds involved in spoilage. We were able connect them to the different bacterial actors and to the influence of packaging type in an overall view. For instance, our results demonstrate a new role of Vibrionaceae in isopropanol production, and of Latilactobacillus fuchuensis and Lactococcus piscium in methanethiol/disylphide production. We also highlight a possible commensal behavior between Leuconostoc carnosum and Latilactobacillus curvatus around 2,3-butanediol metabolism.CONCLUSION: We conclude that our holistic approach combined with large-scale multi-omic data was a powerful strategy to prioritize the role of production parameters, already known in the literature, that shape the evolution and/or the implementation of different meat spoilage scenarios.PMID:37920261 | PMC:PMC10619683 | DOI:10.3389/fmicb.2023.1286661

Front Pharmacol. 2023 Oct 18;14:1258138. doi: 10.3389/fphar.2023.1258138. eCollection 2023.ABSTRACTIn this study, we have employed metabolomics technology in combination with network pharmacology to ascertain the key metabolites and hub genes. The objective was to explore the pathway of Qibai Pingfei Capsule (QBPF) in treating COPD through metabolomics. We identified 96 differential metabolites in the lung tissues of rats belonging to control and model groups, out of which 47 were observed to be critical (VIP >2, p < 0.05). Furthermore, 16 important differential metabolites were reversed after QBPF treatment. Using network pharmacology, we identified 176 core targets of 81 drug-active ingredients. Our comprehensive analysis of network pharmacology and metabolomics enabled us to identify a core target, prostaglandin-endoperoxide synthase 2 (PTGS2), and a core metabolic pathway for glutathione metabolism. Finally, the result of molecular docking showed that PTGS2 had strong binding activity to 18 compounds including Fumarine and Kaempferol, etc.. PTGS2 is a marker of ferroptosis, so we wanted to explore whether QBPF could inhibit ferroptosis in COPD. The results showed that ferroptosis was involved in the pathogenesis of COPD, and QBPF could inhibit the occurrence of ferroptosis. In conclusion, the mechanism of QBPF for treating COPD may be related to PTGS2 expression, glutathione metabolism and ferroptosis.PMID:37920214 | PMC:PMC10618342 | DOI:10.3389/fphar.2023.1258138

Front Cardiovasc Med. 2023 Oct 18;10:1304680. doi: 10.3389/fcvm.2023.1304680. eCollection 2023.NO ABSTRACTPMID:37920177 | PMC:PMC10619719 | DOI:10.3389/fcvm.2023.1304680

J Transl Med. 2023 Nov 2;21(1):776. doi: 10.1186/s12967-023-04637-y.ABSTRACTBACKGROUND: Viral and autoimmune encephalitis may present with similar symptoms, but require different treatments. Thus, there is a need for biomarkers to improve diagnosis and understanding of pathogenesis. We hypothesized that virus-host cell interactions lead to different changes in central nervous system (CNS) metabolism than autoimmune processes and searched for metabolite biomarkers in cerebrospinal fluid (CSF) to distinguish between the two conditions.METHODS: We applied a targeted metabolomic/lipidomic analysis to CSF samples from patients with viral CNS infections (n = 34; due to herpes simplex virus [n = 9], varicella zoster virus [n = 15], enteroviruses [n = 10]), autoimmune neuroinflammation (n = 25; autoimmune anti-NMDA-receptor encephalitis [n = 8], multiple sclerosis [n = 17), and non-inflamed controls (n = 31; Gilles de la Tourette syndrome [n = 20], Bell's palsy with normal CSF cell count [n = 11]). 85 metabolites passed quality screening and were evaluated as biomarkers. Standard diagnostic CSF parameters were assessed for comparison.RESULTS: Of the standard CSF parameters, the best biomarkers were: CSF cell count for viral infections vs. controls (area under the ROC curve, AUC = 0.93), Q-albumin for viral infections vs. autoimmune neuroinflammation (AUC = 0.86), and IgG index for autoimmune neuroinflammation vs. controls (AUC = 0.90). Concentrations of 2 metabolites differed significantly (p < 0.05) between autoimmune neuroinflammation and controls, with proline being the best biomarker (AUC = 0.77). In contrast, concentrations of 67 metabolites were significantly higher in viral infections than controls, with SM.C16.0 being the best biomarker (AUC = 0.94). Concentrations of 68 metabolites were significantly higher in viral infections than in autoimmune neuroinflammation, and the 10 most accurate metabolite biomarkers (AUC = 0.89-0.93) were substantially better than Q-albumin (AUC = 0.86). These biomarkers comprised six phosphatidylcholines (AUC = 0.89-0.92), two sphingomyelins (AUC = 0.89, 0.91), and acylcarnitines isobutyrylcarnitine (C4, AUC = 0.92) and isovalerylcarnitine (C5, AUC = 0.93). Elevated C4 and C5 concentrations suggested dysfunctional mitochondrial β-oxidation and correlated only moderately with CSF cell count (Spearman ρ = 0.41 and 0.44), indicating that their increase is not primarily driven by inflammation.CONCLUSIONS: Changes in CNS metabolism differ substantially between viral CNS infections and autoimmune neuroinflammation and reveal CSF metabolites as pathophysiologically relevant diagnostic biomarkers for the differentiation between the two conditions. In viral CNS infections, the observed higher concentrations of free phospholipids are consistent with disruption of host cell membranes, whereas the elevated short-chain acylcarnitines likely reflect compromised mitochondrial homeostasis and energy generation.PMID:37919735 | DOI:10.1186/s12967-023-04637-y