PubMed

J Immunol Res. 2023 Sep 21;2023:5577850. doi: 10.1155/2023/5577850. eCollection 2023.ABSTRACTThere remains a lack of standard models that have all the characteristics of human diseases. Especially in immunological hepatic fibrosis, the bovine serum albumin (BSA)-induced liver fibrosis models have the same developmental mechanisms as human liver fibrosis models, but have received little attention. We standardized a BSA-induced liver fibrosis model in rats and thoroughly assessed its pathological characteristics. We also used 16S sequencing to assess homeostasis of the intestinal microflora of rats with BSA-induced liver fibrosis and detected various differential metabolites in the serum of these rats using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). We observed stable and unambiguous histological changes in liver tissue morphology and remarkably high concentrations of inflammatory markers in the serum of BSA-induced liver fibrosis rats. In keeping with the fact that BSA induction can cause gut microbiota disorders in rats. UHPLC-MS/MS analysis of rat serum samples in positive-ion mode and negative-ion mode revealed 17 and 25 differential metabolites, respectively. Network analysis revealed that phenylalanine or tyrosine metabolites (e.g., PAGln) were the predominant metabolites in the sera of BSA-induced liver fibrosis rats. Taken together, our results suggest that disorders of amino acid metabolism caused by the gut microbiota may play an important role in the progression of immunological hepatic fibrosis.PMID:37781475 | PMC:PMC10539088 | DOI:10.1155/2023/5577850

Sci Total Environ. 2023 Sep 30:167513. doi: 10.1016/j.scitotenv.2023.167513. Online ahead of print.ABSTRACTHeavy metal pollution is a significant threat to both the environment and living organisms. This is especially vital considering the persistent and cumulative nature of heavy metal exposure, which can lead to severe and chronic health consequences for individuals. Therefore, implementing effective treatments is critical to addressing the serious public health issues posed by heavy metal pollution. In this study, nontargeted metabolomics was carried out to investigate the metabolic changes associated with long-term low-dose intake of mixed heavy metal pollutants (MHMPs) in liver, kidney, and plasma samples of Sprague-Dawley (SD) rats with and without treatment to reveal the underlying toxic effects of MHMPs and the effects of chemoprevention agents, including epigallocatechin-3-gallate (EGCG), trisodium citrate dihydrate (TCD), and glutathione (GSH). In the liver, kidney, and plasma, we observed a total of 21, 69, and 16 metabolites, respectively, exhibiting significant differences (P < 0.05, fold change >1.2 or <0.83, and VIP ≥ 1) between the control group and the mixture group. The findings demonstrated that exposure to MHMPs leads to the dysregulation of numerous metabolic pathways, with a particular emphasis on purine metabolism and aminoacyl-tRNA biosynthesis with upregulated renal purine metabolites and downregulated hepatic purine metabolites as well as renal aminoacyl-tRNA biosynthesis-related metabolites. However, the application of chemical protectants was shown to partially restore the metabolic alterations induced by MHMPs, particularly purine metabolism-related metabolites, including hepatic adenine and renal adenine, guanine, guanosine, adenosine monophosphate (AMP), and hypoxanthine. In addition, liver adenosine, kidney inosine and L-phenylalanine were considered the main regulated sites based on their significant correlations with multiple heavy metals. Our study provides crucial insights into the toxicological mechanisms of heavy metal pollution and has the potential to guide the development of effective preventive strategies.PMID:37783434 | DOI:10.1016/j.scitotenv.2023.167513

Chemosphere. 2023 Sep 30:140329. doi: 10.1016/j.chemosphere.2023.140329. Online ahead of print.ABSTRACTNext-generation risk assessment (NGRA) for environmental chemicals involves a weight of evidence (WoE) framework integrating a suite of new approach methodologies (NAMs) based on points of departure (PoD) obtained from in vitro assays. Among existing NAMs, the omic-based technologies are of particular importance based on the premise that any apical endpoint change indicative of impaired health must be underpinned by some alterations at the omics level, such as transcriptome, proteome, metabolome, epigenome and genome. Transcriptomic assay plays a leading role in providing relatively conservative PoDs compared with apical endpoints. However, it is unclear whether and how parameters measured with other omics techniques predict the cellular response to chemical perturbations, especially at exposure levels below the transcriptomically defined PoD. Multi-omics coverage may provide additional sensitive or confirmative biomarkers to complement and reduce the uncertainty in safety decisions made using targeted and transcriptomics assays. In the present study, we conducted multi-omics studies of transcriptomics, proteomics and phosphoproteomics on two prototype compounds, coumarin and 2,4-dichlorophenoxyacetic acid (2,4-D), with multiple chemical concentrations and time points, to understand the sensitivity of the three omics techniques in response to chemically-induced changes in HepG2. We demonstrated that, phosphoproteomics alterations occur not only earlier in time, but also more sensitive to lower concentrations than proteomics and transcriptomics when the HepG2 cells were exposed to various chemical treatments. The phosphoproteomics changes appear to approach maximum when the transcriptomics alterations begin to initiate. Therefore, it is proximal to the very early effects induced by chemical exposure. We concluded that phosphoproteomics can be utilized to provide a more complete coverage of chemical-induced cellular alteration and supplement transcriptomics-based health safety decision making.PMID:37783352 | DOI:10.1016/j.chemosphere.2023.140329

Semin Cancer Biol. 2023 Sep 30:S1044-579X(23)00127-X. doi: 10.1016/j.semcancer.2023.09.005. Online ahead of print.ABSTRACTAs data-driven science, artificial intelligence (AI) has paved a promising path toward an evolving health system teeming with thrilling opportunities for precision oncology. Notwithstanding the tremendous success of oncological AI in such fields as lung carcinoma, breast tumor and brain malignancy, less attention has been devoted to investigating the influence of AI on gynecologic oncology. Hereby, this review sheds light on the ever-increasing contribution of state-of-the-art AI techniques to the refined risk stratification and whole-course management of patients with gynecologic tumors, in particular, cervical, ovarian and endometrial cancer, centering on information and features extracted from clinical data (electronic health records), cancer imaging including radiological imaging, colposcopic images, cytological and histopathological digital images, and molecular profiling (genomics, transcriptomics, metabolomics and so forth). However, there are still noteworthy challenges beyond performance validation. Thus, this work further describes the limitations and challenges faced in the real-word implementation of AI models, as well as potential solutions to address these issues.PMID:37783319 | DOI:10.1016/j.semcancer.2023.09.005

Eur J Pharmacol. 2023 Sep 30:176082. doi: 10.1016/j.ejphar.2023.176082. Online ahead of print.ABSTRACTAndrographolide (AGP) exerts pharmacological effects when used for the treatment of cardiovascular disease, but the molecular mechanisms underlying its inhibitory effects on the proliferation and migration of vascular smooth muscle cells (VSMCs) and intimal hyperplasia (IH) are unknown. The proliferation and migration of cultured VSMCs were examined using the CCK-8, flow cytometry, and wound healing assays. Expression levels of proteins related to cell proliferation and apoptosis were quantified. A multi-omics analysis with RNA-seq and metabolome was used to explore the potential molecular mechanism of AGP treatment. Additionally, an in vivo model was established through ligation of the left common carotid artery to identify the therapeutic potential of AGP in IH. Molecular docking and western blotting were performed to verify the mechanism discovered with multi-omics analysis. The results showed that AGP inhibited the proliferation and migration of cultured VSMCs in a dose-dependent manner and alleviated IH-related vascular stenosis. AGP significantly downregulated the protein levels of CDK1, CCND1, and BCL2 and upregulated the protein level of BAX. Gene expression profiles showed a total of 3,298 differentially expressed genes (DEGs) after AGP treatment, of which 1,709 DEGs had upregulated expression and 1,589 DEGs had downregulated expression. KEGG enrichment analysis highlighted the PI3K/AKT signaling pathway, verified with the detection of the activation of PI3K and AKT phosphorylation. Further GO enrichment combined with metabolomics analysis showed that AGP inhibition in cultured VSMCs involved the amino acid metabolic process, and the expression levels of the two key factors PRDM16 and EZH2, identified with PPI and docking analysis, were significantly inhibited by AGP treatment. In conclusion, our study showed that AGP inhibited VSMCs proliferation and migration by suppressing the PI3K/AKT signaling pathway and amino acid metabolism, which, in turn, improved IH.PMID:37783303 | DOI:10.1016/j.ejphar.2023.176082

BMC Microbiol. 2023 Oct 3;23(1):282. doi: 10.1186/s12866-023-02983-x.ABSTRACTBACKGROUND: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP.METHODS: We recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls. 16S rRNA sequencing and nontargeting metabolomics were adapted to explore the gut microbiome and fecal metabolites.RESULTS: An increase in richness and a dramatic deviation in composition were found in the gut microbiome in ICP. Decreased Firmicutes and Bacteroidetes abundances and increased Proteobacteria abundances were found in women with severe but not mild ICP compared to healthy pregnant women. Escherichia-Shigella and Lachnoclostridium abundances increased, whereas Ruminococcaceae abundance decreased in ICP group, especially in severe ICP group. The fecal metabolite composition and diversity presented typical variation in severe ICP. A significant increase in bile acid, formate and succinate levels and a decrease in butyrate and hypoxanthine levels were found in women with severe ICP. The MIMOSA model indicated that genera Ruminococcus gnavus group, Lachnospiraceae FCS020 group, and Lachnospiraceae NK4A136 group contributed significantly to the metabolism of hypoxanthine, which was significantly depleted in subjects with severe ICP. Genus Acinetobacter contributed significantly to formate metabolism, which was significantly enriched in subjects with severe ICP.CONCLUSIONS: Women with severe but not mild ICP harbored a unique gut microbiome and fecal metabolites compared to healthy controls. Based on these profiles, we hypothesized that the gut microbiome was involved in bile acid metabolism through metabolites, affecting ICP pathogenesis and development, especially severe ICP.PMID:37784030 | DOI:10.1186/s12866-023-02983-x

BMC Microbiol. 2023 Oct 3;23(1):281. doi: 10.1186/s12866-023-03029-y.ABSTRACTBACKGROUND: Angelica polysaccharides (AP) have numerous benefits in relieving type 2 diabetes (T2D). However, the underlying mechanisms have yet to be fully understood. Recent many reports have suggested that altering gut microbiota can have adverse effects on the host metabolism and contribute to the development of T2D. Here, we successfully established the T2D model using the male KKAy mice with high-fat and high-sugar feed. Meanwhile, the male C57BL/6 mice were fed with a normal feed. T2D KKAy mice were fed either with or without AP supplementation. In each group, we measured the mice's fasting blood glucose, weight, and fasting serum insulin levels. We collected the cecum content of mice, the gut microbiota was analyzed by targeted full-length 16S rRNA metagenomic sequencing and metabolites were analyzed by untargeted-metabolomics.RESULTS: We found AP effectively alleviated glycemic disorders of T2D KKAy mice, with the changes in gut microbiota composition and function. Many bacteria species and metabolites were markedly changed in T2D KKAy mice and reversed by AP. Additionally, 16 altered metabolic pathways affected by AP were figured out by combining metagenomic pathway enrichment analysis and metabolic pathway enrichment analysis. The key metabolites in 16 metabolic pathways were significantly associated with the gut microbial alteration. Together, our findings showed that AP supplementation could attenuate the diabetic phenotype. Significant gut microbiota and gut metabolite changes were observed in the T2D KKAy mice and AP intervention.CONCLUSIONS: Administration of AP has been shown to improve the composition of intestinal microbiota in T2D KKAy mice, thus providing further evidence for the potential therapeutic application of AP in the treatment of T2D.PMID:37784018 | DOI:10.1186/s12866-023-03029-y

Nat Metab. 2023 Oct 2. doi: 10.1038/s42255-023-00893-w. Online ahead of print.ABSTRACTSustained responses to transient environmental stimuli are important for survival. The mechanisms underlying long-term adaptations to temporary shifts in abiotic factors remain incompletely understood. Here, we find that transient cold exposure leads to sustained transcriptional and metabolic adaptations in brown adipose tissue, which improve thermogenic responses to secondary cold encounter. Primary thermogenic challenge triggers the delayed induction of a lipid biosynthesis programme even after cessation of the original stimulus, which protects from subsequent exposures. Single-nucleus RNA sequencing and spatial transcriptomics reveal that this response is driven by a lipogenic subpopulation of brown adipocytes localized along the perimeter of Ucp1hi adipocytes. This lipogenic programme is associated with the production of acylcarnitines, and supplementation of acylcarnitines is sufficient to recapitulate improved secondary cold responses. Overall, our data highlight the importance of heterogenous brown adipocyte populations for 'thermogenic memory', which may have therapeutic implications for leveraging short-term thermogenesis to counteract obesity.PMID:37783943 | DOI:10.1038/s42255-023-00893-w

J Cancer Res Clin Oncol. 2023 Oct 2. doi: 10.1007/s00432-023-05376-9. Online ahead of print.ABSTRACTPURPOSE: The incidence and mortality of lung cancer are continuously rising in recent years. Mitochondrial energy metabolism malfunction is found to be crucial in cancer proliferation and bioenergetic reprogramming, especially for lung cancer. In this study, we attempted to use mitochondrial-targeted drug therapy to change the energy metabolism pattern of cancer cells to inhibit the development of lung cancer, and investigated its mechanism of action and key targets through multi-omics studies.METHODS: In this study, we established the in vivo tumor mouse mode, treated mice with multiple mitochondrial-targeted drug combinations and DDP, severally. Then, we investigated the differences between the 7-drug group with the control group and the DDP treatment group by transcriptomics, proteomics and metabolomics to find the therapeutic targets.RESULTS: We found that mitochondria-targeting drug cocktail therapy, especially the 7-drug regimen, effectively improved mitochondrial metabolism, changed energy supply patterns in lung cancer cells, significantly increased NK cells in tumor tissues, and decreased tumor markers in plasma. Multi-omics analysis informed that the combination of 7-drug could up-regulate mitochondrial oxidative phosphorylation, ATP synthesis and autophagy related genes, and down-regulate proliferation and immune-related genes compared with the control group. By further mapping the protein interaction network, we identified a key target for 7-drug therapy to reverse tumor metabolic reprogramming and validated it in metabolomics.CONCLUSIONS: Mitochondrial-targeted drug cocktail therapy can effectively inhibit the occurrence and development of tumors, through the reprogramming of energy metabolism and the increase in immune cells in tumor tissues. Thus, we provide a novel approach for the treatment of lung cancer and present evidence-based clues for the combined use of targeted mitochondrial drugs.PMID:37783930 | DOI:10.1007/s00432-023-05376-9

Commun Biol. 2023 Oct 2;6(1):1000. doi: 10.1038/s42003-023-05379-9.ABSTRACTEnhancing the dietary properties of rice is crucial to contribute to alleviating hidden hunger and non-communicable diseases in rice-consuming countries. Germination is a bioprocessing approach to increase the bioavailability of nutrients in rice. However, there is a scarce information on how germination impacts the overall nutritional profile of pigmented rice sprouts (PRS). Herein, we demonstrated that germination resulted to increase levels of certain dietary compounds, such as free phenolics and micronutrients (Ca, Na, Fe, Zn, riboflavin, and biotin). Metabolomic analysis revealed the preferential accumulation of dipeptides, GABA, and flavonoids in the germination process. Genome-wide association studies of the PRS suggested the activation of specific genes such as CHS1 and UGT genes responsible for increasing certain flavonoid compounds. Haplotype analyses showed a significant difference (P < 0.05) between alleles associated with these genes. Genetic markers associated with these flavonoids were incorporated into the random forest model, improving the accuracy of prediction of multi-nutritional properties from 89.7% to 97.7%. Deploying this knowledge to breed rice with multi-nutritional properties will be timely to address double burden nutritional challenges.PMID:37783812 | DOI:10.1038/s42003-023-05379-9

Sci Rep. 2023 Oct 2;13(1):16522. doi: 10.1038/s41598-023-43490-3.ABSTRACTGlobally, coral reefs face increasing disease prevalence and large-scale outbreak events. These outbreaks offer insights into microbial and functional patterns of coral disease, including early indicators of disease that may be present in visually-healthy tissues. Outbreak events also allow investigation of how reef-building corals, typically colonial organisms, respond to disease. We studied Pocillopora damicornis during an acute tissue loss disease outbreak on Guam to determine whether dysbiosis was present in visually-healthy tissues ahead of advancing disease lesions. These data reveal that coral fragments with visual evidence of disease are expectedly dysbiotic with high microbial and metabolomic variability. However, visually-healthy tissues from the same colonies lacked dysbiosis, suggesting disease containment near the affected area. These results challenge the idea of using broad dysbiosis as a pre-visual disease indicator and prompt reevaluation of disease assessment in colonial organisms such as reef-building corals.PMID:37783737 | DOI:10.1038/s41598-023-43490-3

Nat Commun. 2023 Oct 2;14(1):5818. doi: 10.1038/s41467-023-41372-w.ABSTRACTLower respiratory tract infections caused by Streptococcus pneumoniae (Spn) are a leading cause of death globally. Here we investigate the bronchial epithelial cellular response to Spn infection on a transcriptomic, proteomic and metabolic level. We found the NAD+ salvage pathway to be dysregulated upon infection in a cell line model, primary human lung tissue and in vivo in rodents, leading to a reduced production of NAD+. Knockdown of NAD+ salvage enzymes (NAMPT, NMNAT1) increased bacterial replication. NAD+ treatment of Spn inhibited its growth while growth of other respiratory pathogens improved. Boosting NAD+ production increased NAD+ levels in immortalized and primary cells and decreased bacterial replication upon infection. NAD+ treatment of Spn dysregulated the bacterial metabolism and reduced intrabacterial ATP. Enhancing the bacterial ATP metabolism abolished the antibacterial effect of NAD+. Thus, we identified the NAD+ salvage pathway as an antibacterial pathway in Spn infections, predicting an antibacterial mechanism of NAD+.PMID:37783679 | DOI:10.1038/s41467-023-41372-w

Poult Sci. 2023 Sep 11;102(12):103102. doi: 10.1016/j.psj.2023.103102. Online ahead of print.ABSTRACTHydrogen sulfide (H2S) is one of the most irritant gases present in rearing stalls that suppress broilers' healthy growth, which is seriously required an effective alleviation method. In this study, Lactobacillus was supplemented to investigate the alleviative effects on broilers reared under consecutive H2S exposure. A total of 180 healthy 1-day-old male AA broilers with similar body weight (40.8 ± 1.0 g) were randomly allotted into the control treatment (CON), the hydrogen sulfide treatment (H2S), and the Lactobacillus supplement under H2S exposure treatment (LAC) for a 42-d-long feeding process. Growth and carcass performances, immunity-related parameters, intestinal development and cecal microbial communities, and blood metabolites were measured. Results showed that Lactobacillus supplement significantly increased the body weight gain (BWG) while reduced the mortality rate, abdominal fat and bursa of fabricius weight during the whole rearing time compared with H2S treatment (P < 0.05). Serum LPS, IL-1β, IL-2, and IL-6 contents were observed significantly increased after H2S treatment while remarkably decreased after Lactobacillus supplementation(P < 0.05). Intestinal morphology results showed a significant higher in the development of ileum villus height (P < 0.05). Cecal microbiota results showed the bacterial composition was significantly altered after Lactobacillus supplement (P < 0.05). Specifically, Lactobacillus supplement significantly decreased the relative abundance of Faecalibacterium, while significantly proliferated the relative abundance of Lactobacillus, Bifidobacterium, Clostridium, and Campylobacter (P<0.05). Metabolic results indicated that Lactobacillus supplement may alleviate the harmful effects caused by H2S through regulating the pyrimidine metabolism, starch and sucrose metabolism, fructose and mannose degradation, and beta-alanine metabolism. In summary, Lactobacillus supplement effectively increased BWG and decreased mortality rate of broilers under H2S exposure by enhancing the body's immune capacity, proliferating beneficial microbes (e.g., Lactobacillus and Bifidobacterium), and regulating the physiological pyrimidine metabolism, starch and sucrose metabolism, and beta-alanine metabolism.PMID:37783191 | DOI:10.1016/j.psj.2023.103102

Phytomedicine. 2023 Sep 21;121:155086. doi: 10.1016/j.phymed.2023.155086. Online ahead of print.ABSTRACTBACKGROUND: Astragaloside IV (AS-IV) is the main active component of "Astragalus membranaceus (Fisch.) Bunge, a synonym of Astragalus propinquus Schischkin (Fabaceae)", which demonstrated to be useful for the treatment of intracerebral hemorrhage (ICH). However, due to the low bioavailability and barrier permeability of AS-IV, the gut microbiota may be an important key regulator for AS-IV to work.OBJECTIVE: To explore the influences of gut microbiota on the effects of AS-IV on ICH.METHODS: Mice were randomly divided into five groups: sham, ICH, and AS-IV-treated groups (25 mg/kg, 50 mg/kg, and 100 mg/kg). Behavioral tests, brain histopathology, and immunohistochemistry analysis were used to evaluate the degree of brain injury. Western blot was employed to verify peri‑hematoma inflammation. The plasma lipopolysaccharide (LPS) leakage, the fluorescein isothiocyanate-dextran permeability, the colonic histopathology, and immunohistochemistry were detected to evaluate the barrier function of intestinal mucosal. Moreover, 16S rDNA sequencing and metabolomic analysis was applied to screen differential bacteria and metabolites, respectively. The correlation analysis was adopted to determine the potential relationship between differential bacteria and critical metabolites or neurological deficits.RESULTS: AS-IV alleviated neurological deficits, neuronal injury and apoptosis, and blood-brain barrier disruption. This compound reduced tumor necrosis factor (TNF)-α expression, increased arginase (Arg)-1 and interleukin (IL)-33 levels around the hematoma. Next, 16S rRNA sequencing indicated that AS-IV altered the gut microbiota, and inhibited the production of conditional pathogenic bacteria. Metabolomic analysis demonstrated that AS-IV regulated the serum metabolic profiles, especially the aminoacid metabolism and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Additionally, AS-IV mitigated intestinal barrier damage and LPS leakage.CONCLUSION: This study provides a new perspective on the use of AS-IV for the treatment of ICH. Among them, gut microbiota and its metabolites may be the key regulator of AS-IV in treating ICH.PMID:37783132 | DOI:10.1016/j.phymed.2023.155086

Talanta. 2023 Sep 22;267:125231. doi: 10.1016/j.talanta.2023.125231. Online ahead of print.ABSTRACTFatty acids (FAs) play a vital physiological role in lipid metabolism, which is reported as potential diagnostic biomarker for various diseases. Thus, it is urgent to develop a credible method that can profile FA metabolism with a holistic view. Here, a targeted strategy to screen FAs was developed by parallel labeling with d0/d6-dansylhydrazine (d0/d6-DnsHz) and using ultra-high performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UPLC-MS/MS) in data-dependent MS/MS (ddMS2) mode. The simple and mild derivatization procedure within 3 h allowed for a significant improvement in sensitivity. Additionally, the characteristic product ions introduced by the derivatization reagent assist to identify the unknown FA species. A quantitation method was established by multiple reaction monitoring (MRM) and the d6-DnsHz tagged standards for each analyte were used as internal standards to overcome the matrix effects. By applying the method to determine FA levels in plasma collected from the esophageal squamous cell carcinoma (ESCC) patients and healthy controls, 65 FA metabolites were characterized and six FAs were found to be altered by the invasion of tumors. The parallel derivatization strategy provides insights into the identification of unknown FAs and paves a new way for targeted metabolomics. Also, this novel method is a powerful tool for characterization and quantification of FAs in biological samples, which shows a great potential application in clinical diagnosis and investigation of disease mechanisms.PMID:37783107 | DOI:10.1016/j.talanta.2023.125231

ACS Nano. 2023 Oct 2. doi: 10.1021/acsnano.3c04462. Online ahead of print.ABSTRACTAs a major late complication of diabetes, diabetic peripheral neuropathy (DPN) is the primary reason for amputation. Nevertheless, there are no wonder drugs available. Regulating dysfunctional mitochondria is a key therapeutic target for DPN. Resveratrol (RSV) is widely proven to guard mitochondria, yet the unsatisfactory bioavailability restricts its clinical application. Tetrahedral framework nucleic acids (tFNAs) are promising carriers due to their excellent cell entrance efficiency, biological safety, and structure editability. Here, RSV was intercalated into tFNAs to form the tFNAs-RSV complexes. tFNAs-RSV achieved enhanced stability, bioavailability, and biocompatibility compared with tFNAs and RSV alone. With its treatment, reactive oxygen species (ROS) production was minimized and reductases were activated in an in vitro model of DPN. Besides, respiratory function and adenosine triphosphate (ATP) production were enhanced. tFNAs-RSV also exhibited favorable therapeutic effects on sensory dysfunction, neurovascular deterioration, demyelination, and neuroapoptosis in DPN mice. Metabolomics analysis revealed that redox regulation and energy metabolism were two principal mechanisms that were impacted during the process. Comprehensive inspections indicated that tFNAs-RSV inhibited nitrosation and oxidation and activated reductase and respiratory chain. In sum, tFNAs-RSV served as a mitochondrial nanoguard (mito-guard), representing a viable drilling target for clinical drug development of DPN.PMID:37782570 | DOI:10.1021/acsnano.3c04462

ACS Nano. 2023 Oct 2. doi: 10.1021/acsnano.3c04990. Online ahead of print.ABSTRACTWith the widespread use of nanoenabled agrochemicals, it is essential to evaluate the food safety of nanomaterials (NMs)-treated vegetable crops in full life cycle studies as well as their potential impacts on human health. Tomato seedlings were foliarly sprayed with 50 mg/L ZnO NMs, including ZnO quantum dots (QDs) and ZnO nanoparticles once per week over 11 weeks. The foliar sprayed ZnO QDs increased fruit dry weight and yield per plant by 39.1% and 24.9, respectively. It also significantly increased the lycopene, amino acids, Zn, B, and Fe in tomato fruits by 40.5%, 15.1%, 44.5%, 76.2%, and 12.8%, respectively. The tomato fruit metabolome of tomatoes showed that ZnO NMs upregulated the biosynthesis of unsaturated fatty acids and sphingolipid metabolism and elevated the levels of linoleic and arachidonic acids. The ZnO NMs-treated tomato fruits were then digested in a human gastrointestinal tract model. The results of essential mineral release suggested that the ZnO QDs treatment increased the bioaccessibility of K, Zn, and Cu by 14.8-35.1% relative to the control. Additionally, both types of ZnO NMs had no negative impact on the α-amylase, pepsin, and trypsin activities. The digested fruit metabolome in the intestinal fluid demonstrated that ZnO NMs did not interfere with the normal process of human digestion. Importantly, ZnO NMs treatments increased the glycerophospholipids, carbohydrates, amino acids, and peptides in the intestinal fluids of tomato fruits. This study suggests that nanoscale Zn can be potentially used to increase the nutritional value of vegetable crops and can be an important tool to sustainably increase food quality and security.PMID:37782568 | DOI:10.1021/acsnano.3c04990

J Sci Food Agric. 2023 Oct 2. doi: 10.1002/jsfa.13011. Online ahead of print.ABSTRACTBACKGROUND: Natto mucus is mainly composed of poly-γ-glutamic acid (γ-PGA), which affects the sensory quality of natto and has some effective functional activities. The soybean metabolites that cause different γ-PGA contents in different fermented natto are unclear.RESULTS: In this study, we use untargeted metabolomics to analyse the metabolites of high-production γ-PGA natto and low-production γ-PGA natto and their fermented substrate soybean. A total of 257 main significantly different metabolites with the same trend among the three comparison groups were screened, of which 114 were downregulated and 143 were upregulated. Through the enrichment of metabolic pathways, the metabolic pathways with significant differences were purine metabolism, nucleotide metabolism, fructose and mannose metabolism, anthocyanin biosynthesis, isoflavonoid biosynthesis, and the pentose phosphate pathway.CONCLUSION: For 114 downregulated main significantly different metabolites with the same trend among the three comparison groups, Bacillus subtilis (natto) may directly decompose them to synthesize γ-PGA. Adding downregulated substances before fermentation or cultivating soybean varieties with the goal of high production of such substances has a great effect on the production of γ-PGA by natto fermentation. The enrichment analysis results showed the main pathways affecting the production of γ-PGA by Bacillus subtilis (natto) using soybean metabolites, which provides a theoretical basis for the production of γ-PGA by soybean and promotes the diversification of natto products. This article is protected by copyright. All rights reserved.PMID:37782527 | DOI:10.1002/jsfa.13011

J Sci Food Agric. 2023 Oct 2. doi: 10.1002/jsfa.13015. Online ahead of print.ABSTRACTBACKGROUND: Flavonoids are vital for developing grapes and wine quality, and manganese deficiency decreases grape berry coloration. However, the effects and underlying mechanisms of action of manganese sulfate on grape metabolic profiles have not been well studied. In this study, three concentrations of manganese sulfate solutions: 0.5 μmol·L-1 (low, L), 5 μmol·L-1 (middle, M, the standard manganese concentration of Hoagland nutrient solution, control), and 1000 μmol·L-1 (high, H) were applied to "Cabernet Sauvignon" grapevine (Vitis vinifera L.) to explore the effect on berry composition.RESULTS: Manganese application effectively improved manganese concentration in grape organs. Furthermore, the concentrations of malvidin 3-O-(6-O-acetyl)-glucoside, malvidin 3-O-glucoside, malvidin-trans-3-O-(6-O-p-coumaryl)-glucoside, and peonidin 3-O-(6-O-acetyl)-glucoside were significantly increased under H treatment. More importantly, weighted gene co-expression network analysis (WGCNA) revealed that the structural genes (VvDFR, VvUFGT, and VvOMT) of flavonoid biosynthesis in brown module were upregulated under H treatment, and positively correlated with malvidin- and peonidin-derived anthocyanin concentrations.CONCLUSIONS: This study suggested that manganese application regulates berry transcriptional and flavonoid metabolic profiles, providing a theoretical basis for improving the color of red grapes and wines. This article is protected by copyright. All rights reserved.PMID:37782112 | DOI:10.1002/jsfa.13015

J Agric Food Chem. 2023 Oct 2. doi: 10.1021/acs.jafc.2c08241. Online ahead of print.ABSTRACTThe relationship between trimethylamine-N-oxide (TMAO), betaine, and choline with acute myocardial infarction (AMI) end point remains unclear. We analyzed plasma TMAO, betaine, and choline concentrations in AMI cases and non-AMI community-dwelling controls by LC-MS/MS to understand how the balance between these metabolites helps to reduce AMI risk. Results showed that the odds ratio (OR) for the highest versus lowest quartiles of betaine was 0.30 (95% CI, 0.10-0.82) after adjustment for AMI risk factors, and the unadjusted OR for quartile 3 versus quartile 1 of TMAO was 2.47 (95% CI, 1.02-6.17) (p < 0.05). The study populations with "high betaine + low TMAO" had a significant protective effect concerning AMI with a multivariable-adjusted OR of 0.20 (95% CI, 0.07-0.55) (p < 0.01). Multivariate linear regression showed that the chronological age was correlated with TMAO concentrations among AMI patients (95% CI, 0.05-3.24, p < 0.01) but not among the controls. This implies a further potential interplay between age and metabolite combination─AMI risk association.PMID:37781984 | DOI:10.1021/acs.jafc.2c08241