PubMed

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

J Alzheimers Dis. 2023 Sep 28. doi: 10.3233/JAD-230683. Online ahead of print.ABSTRACTBACKGROUND: Older adults presenting with dual-decline in cognition and walking speed face a 6-fold higher risk for dementia compared with those showing no decline. We hypothesized that the metabolomics profile of dual-decliners would be unique even before they show signs of decline in cognition and gait speed.OBJECTIVE: The objective of this study was to determine if plasma metabolomics signatures can discriminate dual-decliners from no decliners, purely cognitive decliners, and purely motor decliners prior to decline.METHODS: A retrospective cross-sectional study using baseline plasma for untargeted metabolomics analyses to investigate early signals of later dual-decline status in study participants (n = 76) with convenient sampling. Dual-decline was operationalized as decline in gait speed (>10 cm/s) and cognition (>2 points decline in Montreal Cognitive Assessment score) on at least two consecutive 6-monthly assessments. The participants' decliner status was evaluated 3 years after the blood sample was collected. Pair-wise comparison of detected compounds was completed using principal components and hierarchical clustering analyses.RESULTS: Analyses did not detect any cluster separation in untargeted metabolomes across baseline groups. However, follow-up analyses of specific molecules detected 4 compounds (17-Hydroxy-12-(hydroxymethyl)-10-oxo-8 oxapentacyclomethyl hexopyranoside, Fleroxacin, Oleic acid, and 5xi-11,12-Dihydroxyabieta-8(14),9(11),12-trien-20-oic acid) were at significantly higher concentration among the dual-decliners compared to non-decliners. The pure cognitive decliner group had significantly lower concentration of six compounds (1,3-nonanediol acetate, 4-(2-carboxyethyl)-2-methoxyphenyl beta-D-glucopyranosiduronic acid, oleic acid, 2E-3-[4-(sulfo-oxy)phenyl] acrylic acid, palmitelaidic acid, and myristoleic acid) compared to the non-decliner group.CONCLUSIONS: The unique metabolomics profile of dual-decliners warrants follow-up metabolomics analysis. Results may point to modifiable pathways.PMID:37781807 | DOI:10.3233/JAD-230683

Physiol Genomics. 2023 Oct 2. doi: 10.1152/physiolgenomics.00061.2023. Online ahead of print.ABSTRACTLysine is an essential amino acid that serves as a building block in protein synthesis. Beside this, lysine's metabolic activity has only recently been unraveled. Lysine metabolism is tissue specific and is linked to several renal, cardiovascular and endocrinological diseases through human metabolomics datasets. As a free molecule, lysine takes part in antioxidant response, engages in protein modifications and its chemistry shapes both proteome and metabolome. In the proteome, it is an acceptor for a plethora of posttranslational modifications. In the metabolome it can be modified, conjugated and degraded. Here, we provide an update on integrative physiology of mammalian lysine metabolites such as α-aminoadipic acid, saccharopine, pipecolic acid, and lysine conjugates such as acetyl-lysine, and sugar-lysine conjugates such as advanced glycation end products. We also comment on their emerging associative and mechanistic links to renal disease, hypertension, diabetes and cancer.PMID:37781739 | DOI:10.1152/physiolgenomics.00061.2023

Int J Biol Sci. 2023 Sep 4;19(15):4726-4743. doi: 10.7150/ijbs.85893. eCollection 2023.ABSTRACTGlycine decarboxylase (GLDC) is one of the core enzymes for glycine metabolism, and its biological roles in prostate cancer (PCa) are unclear. First, we found that GLDC plays a central role in glycolysis in 540 TCGA PCa patients. Subsequently, a metabolomic microarray showed that GLDC enhanced aerobic glycolysis in PCa cells, and GLDC and its enzyme activity enhanced glucose uptake, lactate production and lactate dehydrogenase (LDH) activity in PCa cells. Next, we found that GLDC was highly expressed in PCa, was directly regulated by hypoxia-inducible factor (HIF1-α) and regulated downstream LDHA expression. In addition, GLDC and its enzyme activity showed a strong ability to promote the migration and invasion of PCa both in vivo and in vitro. Furthermore, we found that the GLDC-high group had a higher TP53 mutation frequency, lower CD8+ T-cell infiltration, higher immune checkpoint expression, and higher immune exclusion scores than the GLDC-low group. Finally, the GLDC-based prognostic risk model by applying LASSO Cox regression also showed good predictive power for the clinical characteristics and survival in PCa patients. This evidence indicates that GLDC plays crucial roles in glycolytic metabolism, invasion and metastasis, and immune escape in PCa, and it is a potential therapeutic target for prostate cancer.PMID:37781511 | PMC:PMC10539704 | DOI:10.7150/ijbs.85893

Int J Biol Sci. 2023 Aug 21;19(14):4393-4410. doi: 10.7150/ijbs.85712. eCollection 2023.ABSTRACTAkkermansia muciniphila (A. muciniphila), a gram-negative anaerobic bacterium, is selectively decreased in the fecal microbiota of patients with colorectal cancer (CRC), but its molecular mechanism in CRC development remains inconclusive. In this study, we first confirmed the inhibitory effect of A. muciniphila on CRC formation and analyzed the metabolic role of intestinal flora in human Polyps, A-CRA (advanced colorectal adenoma) and CRC samples. To better clarify the role of A. muciniphila in CRC development, a pseudo-germ-free (GF) azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model was established, followed by infection with or without A. muciniphila. Metabolomic analysis and RNA-seq analysis showed tryptophan-mediated aryl hydrocarbon receptor (AhR) was significantly down-regulated in A. muciniphila-infected CRC mice. Then, mice with intestinal specific AhR deficiency (AhRfl/fl Cre) were generated and were used in 2 murine models: AOM/DSS treatment as a model of carcinogen-induced colon cancer and a genetically induced model using ApcMin/+ mice. Notably, AhR deficiency inhibited CRC growth in the AOM/DSS and ApcMin/+ mouse model. Moreover, AhR deficiency inhibited, rather than enhanced, tumor formation and tumor-derived organoids in Apc-deficient cells both in vivo and in vitro by activating Wnt/β-catenin signaling and TCF4/LEF1-dependent transcription. Furthermore, the antitumor effectiveness of A. muciniphila was abolished either in a human colon cancer tumor model induced by subcutaneous transplantation of AhR-silenced CRC cells, or AhR-deficienty spontaneous colorectal cancer model. In conclusion, supplementation with A. muciniphila. protected mice from CRC development by specifically inhibiting tryptophan-mediated AhR/β-catenin signaling.PMID:37781044 | PMC:PMC10535706 | DOI:10.7150/ijbs.85712

Int J Biol Sci. 2023 Aug 21;19(14):4442-4456. doi: 10.7150/ijbs.83468. eCollection 2023.ABSTRACTAs the most common malignancy from mediastinum, the metabolic reprogramming of thymoma is important in its development. Nevertheless, the connection between the metabolic map and thymoma development is yet to be discovered. Thymoma was categorized into three subcategories by unsupervised clustering of molecular markers for metabolic pathway presentation in the TCGA dataset. Different genes and functions enriched were demonstrated through the utilization of metabolic Gene Ontology (GO) analysis. To identify the main contributors in the development of thymic malignancy, we utilized Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The prognosis of thymoma was evaluated by screening the essential pathways and genes using GSVA scores and machine learning classifiers. Furthermore, we integrated the transcriptomics findings with spectrum metabolomics investigation, detected through LC-MS/MS, in order to establish the essential controller network of metabolic reprogramming during thymoma progression. The thymoma prognosis is related to glycosphingolipid biosynthesis-lacto and neolacto series pathway, of what high B3GNT5 indicate poor survival. The investigation revealed that glycosphingolipid charts have a significant impact on metabolic dysfunction and could potentially serve as crucial targets in the clinical advancement of metabolic therapy.PMID:37781041 | PMC:PMC10535712 | DOI:10.7150/ijbs.83468

Front Cell Infect Microbiol. 2023 Sep 14;13:1166366. doi: 10.3389/fcimb.2023.1166366. eCollection 2023.ABSTRACTBACKGROUND: Mixed vaginitis is the infection of the vagina by at least two different pathogens at the same time, both of which contribute to an abnormal vaginal environment leading to signs and symptoms. Baicao Fuyanqing suppository (BCFYQ) is a Miao ethnomedicine, used to treat various vaginitis. The aim of this study was to investigate the efficacy and possible mechanism of BCFYQ in the treatment of mixed vaginitis based on 16S rRNA high-throughput sequencing and metabonomics.METHODS: Escherichia coli and Candida albicans were used to establish mixed vaginitis model in SD rats. Three groups of low, medium and high doses (0.18/0.36/0.64 g.kg-1) were established, and administered vaginally once a day for 6 consecutive days. After the last administration, vaginal pH and IL-1β, IL-2, IL-13 and IgA levels were measured, and the vaginal tissue was examined pathologically. In addition, the vaginal flora was characterised by 16S rRNA, and endogenous metabolites in the vaginal tissue were detected by UHPLC-Q-Exactive MS.RESULTS: Compared with the model group, BCFYQ can reduce the vaginal pH of rats, make it close to the normal group and improve the damaged vaginal epithelial tissue. The results of ELISA showed that BCFYQ decreased the levels of IL-1 β and IL-2 and increased the levels of IL-13 and IgA (P<0.05). In addition, BCFYQ may increase the abundance of vaginal flora, especially Lactobacillus. The differential metabolite enrichment pathway suggests that the therapeutic mechanism of BCFYQ is mainly related to lipid metabolism and amino acid metabolism.CONCLUSION: Our research shows that BCFYQ has a good therapeutic effect on mixed vaginitis. It repairs the damaged vaginal mucosa by regulating the vaginal flora and lipid metabolism disorders to improve the local immune function of the vagina and inhibit the growth and reproduction of pathogens.PMID:37780858 | PMC:PMC10538640 | DOI:10.3389/fcimb.2023.1166366

Heliyon. 2023 Sep 24;9(10):e20413. doi: 10.1016/j.heliyon.2023.e20413. eCollection 2023 Oct.ABSTRACTPalm oil is a vegetable oil that is widely used for cooking and deep-frying because of its affordability. However, repeatedly heated palm oil is also prone to oxidation due to its significant content of unsaturated fatty acids and other chemical toxicants such as glycidyl esters and 3-monochloropropane-1,2-diol (3-MCPD). Initially, the physicochemical properties such as colour, viscosity, peroxide, p-anisidine and total oxidation (TOTOX) of periodically heated palm oil were investigated. Chemical profiling and fingerprinting of six different brands of palm cooking oil during heating cycles between 90 and 360 min were conducted using Fourier transform infrared (FTIR) and 1H Nuclear Magnetic Resonance (NMR) metabolomics. In addition, the multivariate analysis was employed to evaluate the 1H NMR spectroscopic pattern of repeatedly heated palm oil with the corresponding physicochemical properties. The FTIR metabolomics showed significant different of the chemical fingerprinting subjected to heating duration, which in agreement with the result of 1H NMR metabolomics. Partial least squares (PLS) model revealed that most of the physicochemical properties of periodically heated palm oil are positively correlated (R2 values of 0.98-0.99) to their spectroscopic pattern. Based on the findings, the color of the oils darkened with increased heating time. The peroxide value (PV), p-anisidine value (p-AnV), and total oxidation (TOTOX) values increased significantly due to degradation of unsaturated compounds and oxidation products formed. We identified targeted metabolites (probable carcinogens) such as 3-monochloropropane-1,2-diol (3-MCPD) and glycidyl ester (GE), indicating the conversion of 3-MCPD to GE in repeatedly heated oils based on PCA and OPLSDA models. Our correlation analysis of NMR and physicochemical properties has shown that the conversion of 3-MCPD to GE was significantly increased from 180 to 360 min cooking time. The combination spectroscopic techniques with physicochemical properties are a reliable and robust methods to evaluate the characteristics, stability and chemical's structure changes of periodically heated palm oil, which may contribute to probable carcinogens development. This study has proven that combination of NMR and physicochemical analysis may predict the formation of the probable carcinogens of heated cooking oil over time which emphasizing the need to avoid certain heating cycles to mitigate formation of probable carcinogens during cooking process.PMID:37780749 | PMC:PMC10539964 | DOI:10.1016/j.heliyon.2023.e20413

Heliyon. 2023 Sep 21;9(10):e20329. doi: 10.1016/j.heliyon.2023.e20329. eCollection 2023 Oct.ABSTRACTAge-related macular degeneration (AMD) causes irreversible vision-loss among the elderly in industrial countries. Neovascular AMD (nAMD), which refers to late-stage AMD, is characterized by severe vision-threatening choroidal neovascularization (CNV). Herein, we constructed a global metabolic network of nAMD, based on untargeted metabolomic and lipidomic analysis of plasma samples collected from sixty subjects (30 nAMD patients and 30 age-matched controls). Among the nAMD and control groups, 62 and 44 significantly different metabolites were detected in the positive and negative ion modes, respectively. Grouping analysis further showed that lipid and lipid-like molecule-based superclasses contained the highest number of significantly different metabolites. Lipidomic analysis revealed that 53 lipids among the nAMD and control groups differed significantly; these belonged to four major lipid categories (glycerophospholipids, sphingolipids, glycerolipids, and fatty acids). A discriminative biomarker panel comprising 16 metabolites and lipids, which was constructed using multivariate statistical machine learning methods, could effectively identify nAMD cases. Among these 16 compounds, eight were lipids that belonged to three lipid categories (glycerophospholipids, sphingolipids, and prenol lipids). The top three biomarkers with the highest importance scores were all lipids (a glycerophospholipid and two sphingolipids), highlighting the crucial role played by glycerophospholipid and sphingolipid pathways in nAMD. These differences between the metabolic and lipid profiles of nAMD patients and elderly individuals without AMD provide a readout of the overall metabolic status of nAMD. Further insights into the identified discriminative biomarkers may pave the way for future diagnostic and therapeutic interventions for nAMD.PMID:37780745 | PMC:PMC10539639 | DOI:10.1016/j.heliyon.2023.e20329

Front Endocrinol (Lausanne). 2023 Sep 14;14:1212291. doi: 10.3389/fendo.2023.1212291. eCollection 2023.ABSTRACTPM2.5 can cause adverse health effects via several pathways, such as inducing pulmonary and systemic inflammation, penetration into circulation, and activation of the autonomic nervous system. In particular, the impact of PM2.5 exposure on the liver, which plays an important role in metabolism and detoxification to maintain internal environment homeostasis, is getting more attention in recent years. In the present study, C57BL/6J mice were randomly assigned and treated with PM2.5 suspension and PBS solution for 8 weeks. Then, hepatic tissue was prepared and identified by metabolomics analysis and transcriptomics analysis. PM2.5 exposure can cause extensive metabolic disturbances, particularly in lipid and amino acids metabolic dysregulation.128 differential expression metabolites (DEMs) and 502 differently expressed genes (DEGs) between the PM2.5 exposure group and control group were detected. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DEGs were significantly enriched in two disease pathways, non-alcoholic fatty liver disease (NAFLD) and type II diabetes mellitus (T2DM), and three signaling pathways, which are TGF-beta signaling, AMPK signaling, and mTOR signaling. Besides, further detection of acylcarnitine levels revealed accumulation in liver tissue, which caused restricted lipid consumption. Furthermore, lipid droplet accumulation in the liver was confirmed by Oil Red O staining, suggesting hepatic steatosis. Moreover, the aberrant expression of three key transcription factors revealed the potential regulatory effects in lipid metabolic disorders, the peroxisomal proliferative agent-activated receptors (PPARs) including PPARα and PPARγ is inhibited, and the activated sterol regulator-binding protein 1 (SREBP1) is overexpressed. Our results provide a novel molecular and genetic basis for a better understanding of the mechanisms of PM2.5 exposure-induced hepatic metabolic diseases, especially in lipid metabolism.PMID:37780625 | PMC:PMC10539470 | DOI:10.3389/fendo.2023.1212291

Front Plant Sci. 2023 Sep 15;14:1250208. doi: 10.3389/fpls.2023.1250208. eCollection 2023.ABSTRACTThe cultivated grapevine, Vitis vinifera subsp. vinifera, possesses a rich biodiversity with numerous varieties. Each variety adapts differently to varying pedoclimatic conditions, which greatly influence the terroir expression of wine regions. These conditions impact vine growth, physiology, and berry composition, ultimately shaping the unique characteristics and typicity of the wines produced. Nowadays, the potential of the different adaptation capacities of grape varieties has not yet been thoroughly investigated. We addressed this issue by studying two grape varieties, Aglianico and Cabernet Sauvignon, in two different pedoclimatic conditions of Southern Italy. We evaluated and compared the effect of different pedoclimatic conditions on plant physiology, the microbial quality of grapes using Next-Generation Sequencing (NGS) technology, the expression trends of key genes in ripe berries and the concentration of phenolic compounds in grapes and wines by HPLC-MS, HPLC-DAD, NMR and spectrophotometric analyses. Metabolomic and microbiome data were integrated with quantitative gene expression analyses to examine varietal differences and plasticity of genes involved in important oenological pathways. The data collected showed that the phenotypic response of studied grapes in terms of vigor, production, and fruit quality is strongly influenced by the pedoclimatic conditions and, in particular, by soil physical properties. Furthermore, Aglianico grape variety was more influenced than the Cabernet Sauvignon by environmental conditions. In conclusion, the obtained findings not only reinforce the terroir concept and our comprehension of grape's ability to adapt to climate variations but can also have implications for the future usage of grape genetic resources.PMID:37780525 | PMC:PMC10540683 | DOI:10.3389/fpls.2023.1250208

Front Plant Sci. 2023 Sep 14;14:1235687. doi: 10.3389/fpls.2023.1235687. eCollection 2023.ABSTRACTWithering is very important to the quality of Wuyi rock tea. In this study, transcriptomics and metabolomics were used to analyze the effects of different withering methods on tea quality formation. The results showed that sunlight withering (SW) was most beneficial in increasing the gene expression of ubiquinone and other terpenoid-quinone biosynthesis (ko00130), pyruvate metabolism (ko00620), starch and sucrose metabolism (ko00500), and tryptophan metabolism (ko00380) pathways, and increasing the content of nucleotides and derivatives, terpenoids, organic acids and lipids, thus enhancing the mellowness, fresh and brisk taste and aroma of tea. Withering trough withering (WW) was most beneficial in increasing the gene expression of glutathione metabolism (ko00480), phenylpropanoid biosynthesis (ko00940) pathways, increasing the content of phenolic acids and flavonoids, thus enhancing tea bitterness. A comprehensive evaluation of the metabolite content and taste characteristics of tea leaves showed SW to be the best quality and charcoal fire withering (FW) to be the worst quality. This study provided an important basis for guiding the processing of Wuyi rock tea with different flavors.PMID:37780509 | PMC:PMC10538532 | DOI:10.3389/fpls.2023.1235687

Front Plant Sci. 2023 Sep 14;14:1258316. doi: 10.3389/fpls.2023.1258316. eCollection 2023.ABSTRACTPanax notoginseng (P. notoginseng) is an invaluable perennial medicinal herb. However, the roots of P. notoginseng are frequently subjected to severe damage caused by root-knot nematode (RKN) infestation. Although we have observed that P. notoginseng possessed adult-plant resistance (APR) against RKN disease, the defense response mechanisms against RKN disease in different age groups of P. notoginseng remain unexplored. We aimed to elucidate the response mechanisms of P. notoginseng at different stages of development to RKN infection by employing transcriptome, metabolome, and histochemistry analyses. Our findings indicated that distinct age groups of P. notoginseng may activate the phenylpropanoid and flavonoid biosynthesis pathways in varying ways, leading to the synthesis of phenolics, flavonoids, lignin, and anthocyanin pigments as both the response and defense mechanism against RKN attacks. Specifically, one-year-old P. notoginseng exhibited resistance to RKN through the upregulation of 5-O-p-coumaroylquinic acid and key genes involved in monolignol biosynthesis, such as PAL, CCR, CYP73A, CYP98A, POD, and CAD. Moreover, two-year-old P. notoginseng enhanced the resistance by depleting chlorogenic acid and downregulating most genes associated with monolignol biosynthesis, while concurrently increasing cyanidin and ANR in flavonoid biosynthesis. Three-year-old P. notoginseng reinforced its resistance by significantly increasing five phenolic acids related to monolignol biosynthesis, namely p-coumaric acid, chlorogenic acid, 1-O-sinapoyl-D-glucose, coniferyl alcohol, and ferulic acid. Notably, P. notoginseng can establish a lignin barrier that restricted RKN to the infection site. In summary, P. notoginseng exhibited a potential ability to impede the further propagation of RKN through the accumulation or depletion of the compounds relevant to resistance within the phenylpropanoid and flavonoid pathways, as well as the induction of lignification in tissue cells.PMID:37780502 | PMC:PMC10539906 | DOI:10.3389/fpls.2023.1258316

Food Chem X. 2023 Jul 23;19:100809. doi: 10.1016/j.fochx.2023.100809. eCollection 2023 Oct 30.ABSTRACTNine tea cultivars planted in Enshi were selected and processed into "Lichuan black tea". Sensory evaluation showed that cultivar had the greatest influence on taste and aroma quality, including sweetness, umami and concentration of taste, as well as sweet and floral fragrances of aroma. The non-volatile and volatile components were identified by UPLC-Q-TOF/MS and GC-MS, and PCA analysis showed good separation between cultivars, which could cause the difference in quality. Baiyaqilan, Meizhan and Echa 10 had a floral aroma, with obvious difference in their aromatic composition from other cultivars. Moreover, Echa 10 also had a strong sweet aroma. The key aroma components in Echa 10 (with the largest cultivation area) were further investigated by GC-O-MS combined with odor activity value (OAV) analysis, included β-damascenone, phenylethylaldehyde, nonenal, geraniol, linalool, jasmonone, (E)-2-nonenal, β-cyclocitral, (E)-β-ocimene, methyl salicylate, β-ionone, 2,6,10,10-tetramethyl-1-oxaspiro[4.5]dec-6-ene, citral, β-myrcene, nerol, phenethyl alcohol, benzaldehyde, hexanal, nonanoic acid, and jasmin lactone.PMID:37780350 | PMC:PMC10534183 | DOI:10.1016/j.fochx.2023.100809