PubMed

J Agric Food Chem. 2024 Apr 6. doi: 10.1021/acs.jafc.4c01052. Online ahead of print.ABSTRACTPeptide IRW is the first food-derived angiotensin-converting enzyme 2 (ACE2) upregulator. This study aimed to investigate the pharmacokinetic characteristics of IRW and identify the metabolites contributing to its antihypertensive activity in spontaneously hypertensive rats (SHRs). Rats were administered 100 mg of IRW/kg of the body weight via an intragastric or intravenous route. The bioavailability (F %) was determined to be 11.7%, and the half-lives were 7.9 ± 0.5 and 28.5 ± 6.8 min for gavage and injection, respectively. Interestingly, significant blood pressure reduction was not observed until 1.5 h post oral administration, or 2 h post injection, indicating that the peptide's metabolites are likely responsible for the blood pressure-lowering activity. Time-course metabolomics revealed a significant increase in the level of kynurenine, a tryptophan metabolite, in blood after IRW administration. Kynurenine increased the level of ACE2 in cells. Oral administration of tryptophan (W), but not dipeptide IR, lowered the blood pressure and upregulated aortic ACE2 in SHRs. Our study supports the key role of tryptophan and its metabolite, kynurenine, in IRW's blood pressure-lowering effects.PMID:38581395 | DOI:10.1021/acs.jafc.4c01052

J Exp Bot. 2024 Apr 6:erae146. doi: 10.1093/jxb/erae146. Online ahead of print.ABSTRACTPlant defense peptides are paramount endogenous danger signals secreted after a challenge intensifying the plant immune response. The peptidic hormone Systemin (Sys) was shown to participate in resistance in several plant-pathosystems, although the mechanisms behind Sys-IR when exogenously applied remain elusive. We performed proteomic, metabolomic and enzymatic studies to decipher the Sys-induced changes in tomato plants either in the absence or the presence of Botrytis cinerea infection. Sys-treatments triggered direct proteomic rearrangement mostly involved in carbon metabolism and photosynthesis. However, the final induction of defense proteins required concurrent challenge, triggering priming of pathogen-targeted proteins. Conversely, at the metabolomic level, Sys-treated plants showed an alternative behaviour following a general priming profile. Out of the primed metabolites, the flavonoids rutin and isorhamnetin and two alkaloids correlated with the proteins 4-coumarate-CoA-ligase and chalcone-flavanone-isomerase triggered by Sys treatment. In addition, the proteomic and enzymatic analyses revealed that Sys conditioned the primary metabolism towards the production of available sugars that could be fuelling the priming of callose deposition in Sys-treated plants, furthermore PR1 appeared as as key element in Sys-induced resistance. Collectively, the direct induction of proteins and priming of specific secondary metabolites in Sys-treated plants indicated that posttranslational protein regulation is an additional component of priming against necrotrophic fungi.PMID:38581374 | DOI:10.1093/jxb/erae146

Mol Nutr Food Res. 2024 Apr 6:e2300720. doi: 10.1002/mnfr.202300720. Online ahead of print.ABSTRACTSCOPE: The global prevalence of obesity has significantly increased, presenting a major health challenge. High-fat diet (HFD)-induced obesity is closely related to the disease severity of psoriasis, but the mechanism is not fully understood.METHODS AND RESULTS: The study utilizes the HFD-induced obesity model along with an imiquimod (IMQ)-induced psoriasis-like mouse model (HFD-IMQ) to conduct transcriptomics and metabolomic analyses. HFD-induced obese mice exhibits more severe psoriasis-like lesions compared to normal diet (ND)-IMQ mice. The expression of genes of the IL-17 signaling pathway (IL-17A, IL-17F, S100A9, CCL20, CXCL1) is significantly upregulated, leading to an accumulation of T cells and neutrophils in the skin. Moreover, the study finds that there is an inhibition of the branched-chain amino acids (BCAAs) catabolism pathway, and the key gene branched-chain amino transferase 2 (Bcat2) is significantly downregulated, and the levels of leucine, isoleucine, and valine are elevated in the HFD-IMQ mice. Furthermore, the study finds that the peroxisome proliferator-activated receptor gamma (PPAR γ) is inhibited, while STAT3 activity is promoted in HFD-IMQ mice.CONCLUSION: HFD-induced obesity significantly amplifies IL-17 signaling and exacerbates psoriasis, with a potential role played by Bcat2-mediated BCAAs metabolism. The study suggests that BCAA catabolism and PPAR γ-STAT3 exacerbate inflammation in psoriasis with obesity.PMID:38581348 | DOI:10.1002/mnfr.202300720

Biotechnol J. 2024 Apr;19(4):e2300710. doi: 10.1002/biot.202300710.ABSTRACTReconstruction and optimization of biosynthetic pathways can help to overproduce target chemicals in microbial cell factories based on genetic engineering. However, the perturbation of biosynthetic pathways on cellular metabolism is not well investigated and profiling the engineered microbes remains challenging. The rapid development of omics tools has the potential to characterize the engineered microbial cell factory. Here, we performed label-free quantitative proteomic analysis and metabolomic analysis of engineered sabinene overproducing Saccharomyces cerevisiae strains. Combined metabolic analysis andproteomic analysis of targeted mevalonate (MVA) pathway showed that co-ordination of cytosolic and mitochondrial pathways had balanced metabolism, and genome integration of biosynthetic genes had higher sabinene production with less MVA enzymes. Furthermore, comparative proteomic analysis showed that compartmentalized mitochondria pathway had perturbation on central cellular metabolism. This study provided an omics analysis example for characterizing engineered cell factory, which can guide future regulation of the cellular metabolism and maintaining optimal protein expression levels for the synthesis of target products.PMID:38581096 | DOI:10.1002/biot.202300710

Biotechnol J. 2024 Apr;19(4):e2300740. doi: 10.1002/biot.202300740.ABSTRACTβ-Phenylethanol (2-PE), as an important flavor component in wine, is widely used in the fields of flavor chemistry and food health. 2-PE can be sustainably produced through Saccharomyces cerevisiae. Although significant progress has been made in obtaining high-yield strains, as well as improving the synthesis pathways of 2-PE, there still lies a gap between these two fields to unpin. In this study, the macroscopic metabolic characteristics of high-yield and low-yield 2-PE strains were systematically compared and analyzed. The results indicated that the production potential of the high-yield strain might be contributed to the enhancement of respiratory metabolism and the high tolerance to 2-PE. Furthermore, this hypothesis was confirmed through comparative genomics. Meanwhile, transcriptome analysis at key specific growth rates revealed that the collective upregulation of mitochondrial functional gene clusters plays a more prominent role in the production process of 2-PE. Finally, findings from untargeted metabolomics suggested that by enhancing respiratory metabolism and reducing the Crabtree effect, the accumulation of metabolites resisting high 2-PE stress was observed, such as intracellular amino acids and purines. Hence, this strategy provided a richer supply of precursors and cofactors, effectively promoting the synthesis of 2-PE. In short, this study provides a bridge for studying the metabolic mechanism of high-yield 2-PE strains with the subsequent targeted strengthening of relevant synthetic pathways. It also provides insights for the synthesis of nonalcoholic products in S. cerevisiae.PMID:38581087 | DOI:10.1002/biot.202300740

Chem Biodivers. 2024 Apr 5:e202400258. doi: 10.1002/cbdv.202400258. Online ahead of print.ABSTRACTWe presented a strategy utilizing 2D NMR-based metabolomic analysis of crude extracts, categorized by different pharmacological activities, to rapidly identify the primary bioactive components of TCM. It was applied to identify the potential bioactive components from Scutellaria crude extracts that exhibit anti-non-small cell lung cancer (anti-NSCLC) activity. Four Scutellaria species were chosen as the study subjects because of their close phylogenetic relationship, but their crude extracts exhibit significantly different anti-NSCLC activity. Cell proliferation assay was used to assess the anti-NSCLC activity of four species of Scutellaria. 1H-13C HSQC spectra were acquired for the chemical profiling of these crude extracts. Based on the pharmacological classification (PCA, OPLS-DA and univariate hypothesis test) were performed to identify the bioactive constituents in Scutellaria associated with the anti-NSCLC activity. As a result, three compounds, baicalein, wogonin and scutellarin were identified as bioactive compounds. The anti-NSCLC activity of the three potential active compounds were further confirmed via cell proliferation assay. The mechanism of the anti-NSCLC activity by these active constituents was further explored via flow cytometry and western blot analyses. This study demonstrated 2D NMR-based metabolomic analysis of pharmacologically classified crude extracts to be an efficient approach to the identification of active components of herbal medicine.PMID:38581076 | DOI:10.1002/cbdv.202400258

Microbiome. 2024 Apr 5;12(1):70. doi: 10.1186/s40168-024-01781-5.ABSTRACTBACKGROUND: Gut microbiota is significantly influenced by altitude. However, the dynamics of gut microbiota in relation to altitude remains undisclosed.METHODS: In this study, we investigated the microbiome profile of 610 healthy young men from three different places in China, grouped by altitude, duration of residence, and ethnicity. We conducted widely targeted metabolomic profiling and clinical testing to explore metabolic characteristics.RESULTS: Our findings revealed that as the Han individuals migrated from low altitude to high latitude, the gut microbiota gradually converged towards that of the Tibetan populations but reversed upon returning to lower altitude. Across different cohorts, we identified 51 species specifically enriched during acclimatization and 57 species enriched during deacclimatization to high altitude. Notably, Prevotella copri was found to be the most enriched taxon in both Tibetan and Han populations after ascending to high altitude. Furthermore, significant variations in host plasma metabolome and clinical indices at high altitude could be largely explained by changes in gut microbiota composition. Similar to Tibetans, 41 plasma metabolites, such as lactic acid, sphingosine-1-phosphate, taurine, and inositol, were significantly elevated in Han populations after ascending to high altitude. Germ-free animal experiments demonstrated that certain species, such as Escherichia coli and Klebsiella pneumoniae, which exhibited altitude-dependent variations in human populations, might play crucial roles in host purine metabolism.CONCLUSIONS: This study provides insights into the dynamics of gut microbiota and host plasma metabolome with respect to altitude changes, indicating that their dynamics may have implications for host health at high altitude and contribute to host adaptation. Video Abstract.PMID:38581016 | DOI:10.1186/s40168-024-01781-5

BMC Womens Health. 2024 Apr 5;24(1):223. doi: 10.1186/s12905-024-03000-7.ABSTRACTBACKGROUND: Observational studies have revealed that metabolic disorders are closely related to the development of preeclampsia (PE). However, there is still a research gap on the causal role of metabolites in promoting or preventing PE. We aimed to systematically explore the causal association between circulating metabolites and PE.METHODS: Single nucleotide polymorphisms (SNPs) from genome-wide association study (GWAS) of 486 blood metabolites (7,824 participants) were extracted as instrumental variables (P < 1 × 10- 5), GWAS summary statistics for PE were obtained from FinnGen consortium (7,212 cases and 194,266 controls) as outcome, and a two-sample Mendelian randomization (MR) analysis was conducted. Inverse variance weighted (IVW) was set as the primary method, with MR-Egger and weighted median as auxiliary methods; the instrumental variable strength and confounding factors were also assessed. Sensitivity analyses including MR-Egger, Cochran's Q test, MR-PRESSO and leave-one-out analysis were performed to test the robustness of the MR results. For significant associations, repeated MR and meta-analysis were performed by another metabolite GWAS (8,299 participants). Furthermore, significantly associated metabolites were subjected to a metabolic pathway analysis.RESULTS: The instrumental variables for the metabolites ranged from 3 to 493. Primary analysis revealed a total of 12 known (e.g., phenol sulfate, citrulline, lactate and gamma-glutamylglutamine) and 11 unknown metabolites were associated with PE. Heterogeneity and pleiotropy tests verified the robustness of the MR results. Validation with another metabolite GWAS dataset revealed consistency trends in 6 of the known metabolites with preliminary analysis, particularly the finding that genetic susceptibility to low levels of arachidonate (20:4n6) and citrulline were risk factors for PE. The pathway analysis revealed glycolysis/gluconeogenesis and arginine biosynthesis involved in the pathogenesis of PE.CONCLUSIONS: This study identifies a causal relationship between some circulating metabolites and PE. Our study presented new perspectives on the pathogenesis of PE by integrating metabolomics with genomics, which opens up avenues for more accurate understanding and management of the disease, providing new potential candidate metabolic molecular markers for the prevention, diagnosis and treatment of PE. Considering the limitations of MR studies, further research is needed to confirm the causality and underlying mechanisms of these findings.PMID:38580943 | DOI:10.1186/s12905-024-03000-7

Sci Data. 2024 Apr 5;11(1):339. doi: 10.1038/s41597-024-03069-7.ABSTRACTBridging molecular information to ecosystem-level processes would provide the capacity to understand system vulnerability and, potentially, a means for assessing ecosystem health. Here, we present an integrated dataset containing environmental and metagenomic information from plant-associated microbial communities, plant transcriptomics, plant and soil metabolomics, and soil chemistry and activity characterization measurements derived from the model tree species Populus trichocarpa. Soil, rhizosphere, root endosphere, and leaf samples were collected from 27 different P. trichocarpa genotypes grown in two different environments leading to an integrated dataset of 318 metagenomes, 98 plant transcriptomes, and 314 metabolomic profiles that are supported by diverse soil measurements. This expansive dataset will provide insights into causal linkages that relate genomic features and molecular level events to system-level properties and their environmental influences.PMID:38580669 | DOI:10.1038/s41597-024-03069-7

RNA. 2024 Apr 5:rna.079912.123. doi: 10.1261/rna.079912.123. Online ahead of print.ABSTRACTRibosomes translate mRNA into proteins and are essential for every living organism. In eukaryotes both ribosomal subunits are rapidly assembled in a strict hierarchical order, starting in the nucleolus with transcription of a common precursor ribosomal RNA (pre-rRNA). This pre-rRNA encodes three of the four mature rRNAs which are formed by several, consecutive endonucleolytic and exonucleolytic processing steps. Historically, Northern Blots are used to analyze the variety of different pre-rRNA species, only allowing rough length estimations. Although this limitation can be overcome with Primer Extension, both approaches often use radioactivity and are time consuming and costly. Here we present "Riboprobing" a reverse transcription-based workflow extended by linker ligation for easy and fast detection and characterization of various pre-rRNA species and their 5` as well as 3` ends. Using standard molecular biology lab equipment, our technique allows reliable discrimination of pre-rRNA species not resolved by Northern Blotting (e.g.: 27SA2, 27SA3 and 27SB). The method can be successfully used for analysis of total cell extracts as well as purified pre-ribosomes for a straightforward evaluation of the impact of mutant gene versions or inhibitors. In the course of method development, we identified and characterized a hitherto undescribed aberrant pre-rRNA, arising from LiCl inhibition. This pre-rRNA fragment spans from processing site A1 to E, forming a small RNP that is lacking most early joining assembly factors. This finding expands our knowledge of how the cell deals with severe pre-rRNA processing defects and demonstrates the strict requirement for the 5'ETS for the assembly process.PMID:38580456 | DOI:10.1261/rna.079912.123

Biochim Biophys Acta Mol Cell Res. 2024 Apr 3:119721. doi: 10.1016/j.bbamcr.2024.119721. Online ahead of print.ABSTRACTMetabolic reprogramming is considered as a hallmark of cancer and is clinically exploited as a novel target for therapy. The E2F transcription factor-1 (E2F1) regulates various cellular processes, including proliferative and metabolic pathways, and acts, depending on the cellular and molecular context, as an oncogene or tumor suppressor. The latter is evident by the observation that E2f1-knockout mice develop spontaneous tumors, including uterine sarcomas. This dual role warrants a detailed investigation of how E2F1 loss impacts metabolic pathways related to cancer progression. Our data indicate that E2F1 binds to the promoter of several glutamine metabolism-related genes. Interestingly, the expression of genes in the glutamine metabolic pathway were increased in mouse embryonic fibroblasts (MEFs) lacking E2F1. In addition, we confirm that E2f1-/- MEFs are more efficient in metabolizing glutamine and producing glutamine-derived precursors for proliferation. Mechanistically, we observe a co-occupancy of E2F1 and MYC on glutamine metabolic promoters, increased MYC binding after E2F1 depletion and that silencing of MYC decreased the expression of glutamine-related genes in E2f1-/- MEFs. Analyses of transcriptomic profiles in 29 different human cancers identified uterine sarcoma that showed a negative correlation between E2F1 and glutamine metabolic genes. CRISPR/Cas9 knockout of E2F1 in the uterine sarcoma cell line SK-UT-1 confirmed elevated glutamine metabolic gene expression, increased proliferation and increased MYC binding to glutamine-related promoters upon E2F1 loss. Together, our data suggest a crucial role of E2F1 in energy metabolism and metabolic adaptation in uterine sarcoma cells.PMID:38580088 | DOI:10.1016/j.bbamcr.2024.119721

J Mol Biol. 2024 Apr 3:168559. doi: 10.1016/j.jmb.2024.168559. Online ahead of print.ABSTRACTUpstream open reading frames (uORFs) are cis-acting elements that can dynamically regulate the translation of downstream ORFs by suppressing downstream translation under basal conditions and, in some cases, increasing translation under stress conditions. Computational and empirical methods have identified uORFs in the 5'-UTRs of approximately half of all mouse and human transcripts, making uORFs one the largest regulatory elements known. Because the prevailing dogma was that eukaryotic mRNAs produce a single functional protein, the peptides and small proteins, or microproteins, encoded by uORFs are under studied. We hypothesized that a uORF in the SLC35A4 mRNA is producing a functionalmicroprotein (SLC35A4-MP) because of its conserved amino acid sequence. Through a series of biochemical and cellular experiments, we find that the 103-amino acid SLC35A4-MP is a single-pass transmembrane inner mitochondrial membrane (IMM) microprotein. The IMM contains the protein machinery crucial for cellular respiration and ATP generation, and loss of function studies with SLC35A4-MP significantly diminish maximal cellular respiration, indicating a vital role for this microprotein in cellular metabolism. The findings add to the growing list of functional microproteins and, more generally, indicate that uORFs that encode conserved microproteins are an untapped reservoir of functional microproteins.PMID:38580077 | DOI:10.1016/j.jmb.2024.168559

Comp Biochem Physiol C Toxicol Pharmacol. 2024 Apr 3:109908. doi: 10.1016/j.cbpc.2024.109908. Online ahead of print.ABSTRACTIn recent years, saline-alkaline aquaculture development has become an important measure for China to expand its fishery development space to ensure food safety. Previous studies have verified that salinity and alkalinity positively influence the quality of Chinese mitten crabs (Eriocheir sinensis). However, the regulatory mechanism of E. sinensis endures saline-alkaline stress which remains obscure. This study investigated the metabolic changes in puberty-molting E. sinensis gills exposed to freshwater (FW), sodium chloride salinity of 5 ppt (SW), and carbonate alkalinity 10.00 mmol/L (AW) for 50 days using untargeted liquid chromatography-mass spectrometry metabolomics (LC-MS). A total of 5802 (positive-ion mode) and 6520 (negative-ion mode) peaks were extracted by LC-MS, respectively. A total of 188 (50 upregulated and 138 downregulated), 141 (94 upregulated and 47 downregulated), and 130 (87 upregulated and 43 downregulated) significantly regulated metabolites (SRMs) were observed in the FW-SW, FW-AW, and SW-AW treatments, respectively, wherein 42 generic SRMs were also found by Venn diagram analysis. Seven of the top 10 SRMs with the highest (variable importance in projection) VIP values were similarly identified in FW-SW and SW-AW. Integrated analysis of key metabolic pathways revealed glycerophospholipid, choline in cancer, phenylalanine, and butanoate metabolism. Overall, significant differences were observed in the metabolites and key metabolic pathways of E. sinensis gill exposed to salinity and alkalinity stress. These results will be helpful in understanding the environmental adaptability of aquatic crustaceans to saline-alkaline water.PMID:38580071 | DOI:10.1016/j.cbpc.2024.109908

Steroids. 2024 Apr 3:109420. doi: 10.1016/j.steroids.2024.109420. Online ahead of print.ABSTRACTThe use of steroids in livestock animals is a source of concern for consumers because of the risks associated with the presence of their residues in foodstuffs of animal origin. Technological advances such as mass spectrometry have made it possible to play a fundamental role in controlling such practices, firstly for the discovery of marker metabolites but also for the monitoring of these compounds under the regulatory framework. Current control strategies rely on the monitoring of either the parent drug or its metabolites in various matrices of interest. As some of these steroids also have an endogenous status specific strategies have to be applied for control purposes. This review aims to provide a comprehensive and up-to-date knowledge of analytical strategies, whether targeted or non-targeted, and whether they focus on markers of exposure or effect in the specific context of chemical food safety regarding the use of anabolic steroids in livestock. The role of new approaches in data acquisition (e.g. ion mobility), processing and analysis, (e.g. molecular networking), is also discussed.PMID:38580048 | DOI:10.1016/j.steroids.2024.109420

Environ Res. 2024 Apr 3:118874. doi: 10.1016/j.envres.2024.118874. Online ahead of print.ABSTRACT3-Methylindole (Skatole), a degradation product of tryptophan produced by intestinal microbial activity, significantly contributes to odor nuisance. Its adverse effects on animal welfare, human health, and environmental pollution have been noted. However, it is still unclear whether the intestinal microbiota mediates the impact of selenium (Se) on skatole production and what the underlying mechanisms remain elusive. A selenized glucose (SeGlu) derivative is a novel organic selenium compound. In this study, a diverse range of dietary SeGlu-treated levels, including SeGlu-deficient (CK), SeGlu-adequate (0.15 mg Se per L), and SeGlu-supranutritional (0.4 mg Se per L) conditions, were used to investigate the complex interaction of SeGlu on intestinal microbiome and serum metabolome changes in male Sprague-Dawley (SD) rats. The study showed that SeGlu supplementation enhanced the antioxidant ability in rats, significantly manifested in the increases of the activity of catalase (CAT) and glutathione peroxidase (GSH-Px), while no change in the level of malonaldehyde (MDA). Metagenomic sequencing analysis verified that the SeGlu treatment group significantly increased the abundance of beneficial microorganisms such as Clostridium, Ruminococcus, Faecalibacterium, Lactobacillus, and Alloprevotella while reducing the abundance of opportunistic pathogens such as Bacteroides and Alistipes significantly. Further metabolomic analysis revealed phenylalanine, tyrosine, and tryptophan biosynthesis changes in the SeGlu treatment group. Notably, the biosynthesis of indole, a critical pathway, was affected by SeGlu treatment, with several crucial enzymes implicated. Correlation analysis demonstrated strong associations between specific bacterial species - Treponema, Bacteroides, and Ruminococcus, and changes in indole and derivative concentrations. Moreover, the efficacy of SeGlu-treated fecal microbiota was confirmed through fecal microbiota transplantation, leading to a decrease in the concentration of skatole in rats. Collectively, the analysis of microbiota and metabolome response to diverse SeGlu levels suggests that SeGlu is a promising dietary additive in modulating intestinal microbiota and reducing odor nuisance in the livestock and poultry industry.PMID:38579995 | DOI:10.1016/j.envres.2024.118874

Reproduction. 2024 Apr 1:REP-23-0472. doi: 10.1530/REP-23-0472. Online ahead of print.ABSTRACTAnecdotal experience suggests horse mares have less post-breeding inflammation and better fertility when bred with donkeys. This study aimed to compare the post-breeding inflammatory response of mares exposed to donkey and horse semen and seminal plasma and evaluate the proteome and metabolome of donkey and horse sperm and seminal plasma. Uterine edema, intrauterine fluid accumulation, PMNs on cytology, and concentrations of progesterone, and pro- and anti-inflammatory cytokines (IL1, IL1, IL4, IL6, CXCL8, IL10) concentrations were assessed pre-and post-infusion of semen and seminal plasma (donkey and horse). The metabolome and proteome were analyzed by LC-MS/MS. Mare cycles bred with horse semen had a greater progesterone concentration than those cycles bred with donkey semen at 8 days post-ovulation (P=0.046). At 6 h post-infusion, the inflammatory response due to the donkey semen tended to be lower (P=0.074). Donkey seminal plasma had anti-inflammatory properties compared to horse semen and seminal plasma, as determined by fewer neutrophils on uterine cytology (P<0.05). Horse semen induced resulted in a greater concentrations of IL6 and lesser concentrations of IL1 (P<0.05). Concentrations of PGE1, PGE3, and lactoferrin PGE1, PGE3, and lactoferrin concentrations were significantly more abundant in donkey sperm and seminal plasma. Prostaglandins play an important role in immunomodulation and might contribute to the response triggered in inter-species breeding. In conclusion, breeding horse mares with donkey semen induces a similar post-breeding endometritis to horse semen. Donkey seminal plasma results in a lower post-infusion inflammatory response than other combinations in the immediate post-breeding.PMID:38579760 | DOI:10.1530/REP-23-0472

Food Chem. 2024 Mar 31;449:139207. doi: 10.1016/j.foodchem.2024.139207. Online ahead of print.ABSTRACTTetrastigma hemsleyanum root is a popular functional food in China, and the price varies based on the origin of the product. The link between the origin, metabolic profile, and bioactivity of T. hemsleyanum must be investigated. This study compares the metabolic profiles of 254 samples collected from eight different areas with 49 potential key chemical markers using plant metabolomics. The metabolic pathways of the five critical flavonoid metabolites were annotated and enriched using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Moreover, a random forest model aiding the spectrum-effect relationship analysis was developed for the first time indicating catechin and darendoside B as potential quality markers of antioxidant activity. The findings of this study provide a comprehensive understanding of the chemical composition and bioactive compounds of T. hemsleyanum as well as valuable information on the evaluation of the quality of various samples and products in the market.PMID:38579655 | DOI:10.1016/j.foodchem.2024.139207

Phytomedicine. 2024 Mar 20;129:155559. doi: 10.1016/j.phymed.2024.155559. Online ahead of print.ABSTRACTBACKGROUND: Osteoclast plays an important role in maintaining the balance between bone anabolism and bone catabolism. The abnormality of osteoclast is closely related to osteolytic bone diseases such as osteoporosis, rheumatoid arthritis and tumor bone metastasis.PURPOSE: We aim to search for natural compound that may suppress osteoclast formation and function.STUDY DESIGN: In this study, we assessed the impact of Dauricine (Dau) on the formation and function of osteoclasts in vitro, as well as its potential in preventing bone loss in an ovariectomy mouse model in vivo.METHODS: Multiple in vitro experiments were carried out, including osteoclastogenesis, podosomal belt formation, bone resorption assay, RNA-sequencing, real-time quantitative PCR, ROS level detection, surface plasmon resonance assay, luciferase assay and western blot. To verify the effect in vivo, an ovariectomized mouse model (OVX model) was constructed, and bone parameters were measured using micro-CT and histology. Furthermore, metabolomics analysis was performed on blood serum samples from the OVX model.RESULTS: In vitro experiments demonstrated that Dau inhibits RANKL-induced osteoclastogenesis, podosomal belt formation, and bone resorption function. RNA-sequencing results revealed that Dau significantly suppresses genes related to osteoclast. Functional enrichment analysis indicated that Dau's inhibition of osteoclasts may be associated with NF-κB signaling pathway and reactive oxygen metabolism pathway. Molecular docking, surface plasmon resonance assay and western blot analysis further confirmed that Dau inhibits RANKL-induced osteoclastogenesis by modulating the ROS/NF-κB/NFATc1 pathway. Moreover, administration of Dau to OVX-induced mice validated its efficacy in treating bone loss disease.CONCLUSION: Dau prevents OVX-induced bone loss by inhibiting osteoclast activity and bone resorption, potentially offering a new approach for preventing and treating metabolic bone diseases such as osteoporosis. This study provides innovative insights into the inhibitory effects of Dau in an in vivo OVX model and elucidates the underlying mechanism.PMID:38579642 | DOI:10.1016/j.phymed.2024.155559

J Hazard Mater. 2024 Apr 3;470:134204. doi: 10.1016/j.jhazmat.2024.134204. Online ahead of print.ABSTRACTSelenium (Se) plays a critical role in diverse biological processes and is widely used across manufacturing industries. However, the contamination of Se oxyanions also poses a major public health concern. Microbial transformation is a promising approach to detoxify Se oxyanions and produce elemental selenium nanoparticles (SeNPs) with versatile industrial potential. Yeast-like fungi are an important group of environmental microorganisms, but their mechanisms for Se oxyanions reduction remain unknown. In this study, we found that Aureobasidium melanogenum I15 can reduce 1.0 mM selenite by over 90% within 48 h and efficiently form intracellular or extracellular spherical SeNPs. Metabolomic and proteomic analyses disclosed that A. melanogenum I15 evolves a complicated selenite reduction mechanism involving multiple metabolic pathways, including the glutathione/glutathione reductase pathway, the thioredoxin/thioredoxin reductase pathway, the siderophore-mediated pathway, and multiple oxidoreductase-mediated pathways. This study provides the first report on the mechanism of selenite reduction and SeNPs biogenesis in yeast-like fungi and paves an alternative avenue for the bioremediation of selenite contamination and the production of functional organic selenium compounds.PMID:38579586 | DOI:10.1016/j.jhazmat.2024.134204

Food Chem. 2024 Mar 31;448:139202. doi: 10.1016/j.foodchem.2024.139202. Online ahead of print.ABSTRACTExisting studies on post-harvest processing of edible roses have mainly focused on processing techniques and physicochemical properties of the final dried products, with limited studies on how changes in metabolites during processing affect the quality of these products. This study investigated changes in water content and status, enzyme activity, phenolic compounds, and volatile and non-volatile compounds during processing and revealed the mechanisms by which post-harvest processing (drying without blanching (WBD) and drying with blanching (BD)) affects the quality of dried roses by establishing their correlations. Results showed that the blanching reduced the relative content of free water and water activity, thus reducing the subsequent drying time and enzyme activity. The BD method caused higher levels of phenolic compounds than the WBD method in terms of gallic acid, ellagic acid, epicatechin, and quercetin. The OPLS-DA analysis identified 6 differential volatiles out of 72 detected volatiles, contributing to the unique aroma of dried roses by activating olfactory receptors through hydrogen bonding and hydrophobic interactions. 58 differential metabolites were screened from 964 non-volatile metabolites. KEGG pathway analysis revealed that the changes in volatile and non-volatile metabolites induced by different processing methods were due to the effect of blanching on glutathione and fatty acid metabolism. These findings provide a comprehensive understanding of how post-harvest processing affects the quality of dried roses.PMID:38579556 | DOI:10.1016/j.foodchem.2024.139202