PubMed

Front Plant Sci. 2024 Nov 13;15:1480588. doi: 10.3389/fpls.2024.1480588. eCollection 2024.ABSTRACTAmmonium is the preferred N nutrition over nitrate for some plant species, but it is toxic to many other plant species and induces senescence at high concentrations. The duckweed Wolffia microscopica (Griff.) Kurz is the smallest and fast-growing angiosperm. It is highly sensitive to ammonium and has a short lifespan on media containing 0.5 mM or higher ammonia. This feature makes it a potential model plant to screen for anti-aging microorganisms. By co-culturing W. microscopica with endophytic microorgainisms isolated from rubber tree, we screened out an Aspergillus sclerotiorum strain ITBB2-31 that significantly increased the lifespan and the biomass of W. microscopica. Interestingly, both filter-sterilized and autoclaved exudates of ITBB2-31 increased the lifespan of W. microscopica cultures from 1 month to at least 7 months. Meanwhile, the exudates also showed strong anti-aging effects on cassava and the rubber tree leaves and increased chlorophyll contents by 50% - 350%. However, high contents of filter-sterilized exudates inhibited the growth of W. microscopica while extending its lifespan, indicating that there were heat-sensitive growth-inhibiting agents in the exudates as well. Comparative metabolome analysis of the filter-sterilized and autoclaved exudates revealed multiple heat-stable anti-aging and heat-sensitive growth-inhibiting compounds. Our results suggest that W. microscopica can be served as a rapid and efficient model plant to screen for plant anti-aging microorganisms.PMID:39619847 | PMC:PMC11605829 | DOI:10.3389/fpls.2024.1480588

Front Plant Sci. 2024 Nov 15;15:1463666. doi: 10.3389/fpls.2024.1463666. eCollection 2024.ABSTRACTPlant metabolites are the components endowing traditional Chinese medicine (TCM) with therapeutic effects, and, simultaneously, they are the primary targets for quality control. From germplasm selection and origin determination to field management, growth duration, harvesting and processing, and, finally, storage and transportation, each step profoundly influences TCM quality. The complexity of these plant or herb metabolites poses numerous quality control challenges. Metabolomics, as a comprehensive and systematic approach, has demonstrated value in this field. This technique not only meets the requirements for studying the complex mechanisms of TCM but also has significant advantages in identifying the TCM components, including active components. Therefore, in this article, several key factors affecting the chemical characteristics and quality traits of TCM, including their origin, harvesting period, medicinal parts, and processing methods, are researched. Additionally, the current challenges of integrating metabolomics with other omics technologies (transcriptomics, spatial metabolomics, etc.) are discussed. Furthermore, a future development trends and prospects are highlighted. With the continuous deepening of research and ongoing updates in technological capabilities, metabolomics will play an increasingly important role in the quality control of TCM, providing more scientific and robust support for quality assurance and safety evaluation.PMID:39619843 | PMC:PMC11604444 | DOI:10.3389/fpls.2024.1463666

Front Cell Infect Microbiol. 2024 Nov 15;14:1497965. doi: 10.3389/fcimb.2024.1497965. eCollection 2024.ABSTRACTBACKGROUND: Herbal products have long been utilized as remedies for various disease conditions, including infections. This study investigates the therapeutic mechanism of a traditional Chinese herbal combination in treating high-risk HPV infections.METHODS: The herbal formula was prepared using common herbs: dry Millettia speciosa, Guanzhong (a spermatophyte), Sarsaparilla, White Fruit, and Cockscomb Flower. Eight female patients diagnosed with high-risk HPV were enrolled from January to September 2023 at Shenzhen Hospital of Beijing University of Traditional Chinese Medicine. Cervicovaginal secretions were collected before and after treatment with the herbal remedy and analyzed using non-targeted metabolomics techniques. In vitro studies were conducted using HeLa cells to determine the optimal effective concentration of the remedy, assessed via the CCK8 method. The proliferation and migration of HeLa cells were evaluated using Transwell assays. Quantitative PCR was employed to measure mRNA levels of endothelial-to-mesenchymal transition (EndMT) markers, including VE-Cadherin, eNOS, α-SMA, and Snail.RESULTS: In vivo, significant alterations in cervicovaginal secretion metabolites post-treatment were observed through PCA, OPLS-DA, and volcano plot analyses. KEGG enrichment analysis highlighted crucial signaling pathways such as arginine and proline metabolism, purine metabolism, glycerophospholipid metabolism, and phenylalanine metabolism, indicating the herbal combination's systemic effects on patients. In vitro experiments demonstrated a dose-dependent reduction in HeLa cell proliferation and migration, confirmed by scratch and Transwell assays. Additionally, qPCR analysis revealed down-regulation of α-SMA and Snail, and up-regulation of VE-Cadherin and eNOS, suggesting inhibition of EndMT in HeLa cells.CONCLUSION: The traditional Chinese herbal combination modulates key metabolic pathways in vivo and inhibits EndMT in vitro, while reducing HeLa cell proliferation and migration. These findings highlight its potential as a therapeutic approach for managing HPV infections, bridging traditional practices with scientific research.PMID:39619658 | PMC:PMC11604629 | DOI:10.3389/fcimb.2024.1497965

Curr Res Food Sci. 2024 Nov 12;9:100924. doi: 10.1016/j.crfs.2024.100924. eCollection 2024.ABSTRACTMultiple gastrointestinal disorders are associated with impaired gut microbiota. Probiotic Lacticaseibacillus rhamnosus can improve bowel disorder, however, the action mechanism is poorly understood. We integrated multi-omics data from the gut metagenome, metabolome, and colon transcriptome of constipated mice underlying L. rhamnosus LRJ-1 treatment to provide insights into host-microbial metabolic pathway. We found that oral administration of L. rhamnosus LRJ-1 alleviated constipation in mice accompanied by the increased abundances of fecal γ-aminobutyric acid (GABA) and intestinal commensal Bacteroides, and the activation of host GABAergic synapses. B. uniformis was the most enriched Bacteroides species in constipated mice treated with L. rhamnosus LRJ-1, and contributed to the increased abundance of GABA in the gut. Administration of either B. uniformis ATCC 8492 or GABA alleviated constipation and increased gastrointestinal motility in constipated mice. Knockout of the GABA biosynthetic gad gene in B. uniformis ATCC 8492 decreased GABA production and blocked its beneficial effects on constipation. These results confirm the therapeutic potential of L. rhamnosus LRJ-1 in alleviating constipation through promoting gut commensal Bacteroides-derived GABA production. Targeting the gut microbiome to regulate GABA production may open new insights for efficient constipation treatment.PMID:39619641 | PMC:PMC11605182 | DOI:10.1016/j.crfs.2024.100924

Hemasphere. 2024 Nov 28;8(12):e70001. doi: 10.1002/hem3.70001. eCollection 2024 Dec.ABSTRACTThe transcription factors STAT3, STAT5A, and STAT5B steer hematopoiesis and immunity, but their enhanced expression and activation promote acute myeloid leukemia (AML) or natural killer/T cell lymphoma (NKCL). Current therapeutic strategies focus on blocking upstream tyrosine kinases to inhibit STAT3/5, but these kinase blockers are not selective against STAT3/5 activation and frequent resistance causes relapse, emphasizing the need for targeted drugs. We evaluated the efficacy of JPX-0700 and JPX-0750 as dual STAT3/5 binding inhibitors promoting protein degradation. JPX-0700/-0750 decreased the mRNA and protein levels of STAT3/5 targets involved in cancer survival, metabolism, and cell cycle progression, exhibiting nanomolar to low micromolar efficacy. They induced cell death and growth arrest in both AML/NKCL cell lines and primary AML patient blasts. We found that both AML/NKCL cells hijack STAT3/5 signaling through either upstream activating mutations in kinases, activating mutations in STAT3, mutational loss of negative STAT regulators, or genetic gains in anti-apoptotic, pro-proliferative, or epigenetic-modifying STAT3/5 targets. This emphasizes a vicious cycle for proliferation and survival through STAT3/5. Both JPX-0700/-0750 treatment reduced leukemic cell growth in human AML or NKCL xenograft mouse models significantly, being well tolerated by mice. Synergistic cell death was induced upon combinatorial use with approved chemotherapeutics in AML/NKCL cells.PMID:39619245 | PMC:PMC11603092 | DOI:10.1002/hem3.70001

Int J Nanomedicine. 2024 Nov 26;19:12557-12581. doi: 10.2147/IJN.S491471. eCollection 2024.ABSTRACTBACKGROUND: Owing to the distinctive advantages of mesenchymal stem cell-derived exosomes (MSCs-exo), these vesicles have emerged as a pivotal research focus in regenerative medicine, surpassing their MSC counterparts. Quercetin (Qr), widely recognized for its potent anti-inflammatory and antioxidant activities, demonstrates substantial potential in enhancing tissue repair processes. This study delves into the role of quercetin-pretreated MSC-derived exosomes (MSCsQr-exo) in accelerating the healing of diabetic wounds.METHODS: MSCsQr-exo were isolated from quercetin-pretreated MSCs and applied to fibroblasts to evaluate changes in cell function. An in vitro DSW rat model was also developed, and the rats were treated with MSCsQr-exo to assess wound healing progression. Fecal samples were collected for 16S rRNA sequencing and untargeted metabolomics to analyze changes in gut microbiota and metabolic profiles.RESULTS: MSCsQr-exo significantly enhanced fibroblast proliferation and migration while improving the therapeutic efficacy of MSCs-exo in DSW treatment. Gut microbiota and metabolomic analyses revealed marked changes in DSW rats, with MSCsQr-exo effectively alleviating dysbiosis. MSCsQr-exo upregulated Faecalibacterium abundance and regulated arachidonic acid metabolism in both the arachidonic and linoleic acid pathways. Firmicutes and Enterobacteriaceae influenced the arachidonic acid pathway by modulating 14.15-EET expression levels.CONCLUSION: MSCsQr-exo facilitate DSW wound healing through modulation of dysbiotic gut microbiota linked to DSW pathology. This discovery offers novel therapeutic avenues and research trajectories for enhancing DSW recovery.PMID:39619055 | PMC:PMC11608046 | DOI:10.2147/IJN.S491471

J Inflamm Res. 2024 Nov 27;17:9857-9873. doi: 10.2147/JIR.S474040. eCollection 2024.ABSTRACTPURPOSE: The effects of 5-methoxytryptophan (5-MTP) on mitophagy in sepsis-induced acute kidney injury (S-AKI) and its possible role in the Nrf2/HO-1 signaling pathway are unclear. In this study, we aimed to examine the levels of serum 5-MTP and mitophagy in patients with S-AKI and to evaluate the influence of 5-MTP on a lipopolysaccharide(LPS)-induced AKI model. Additionally, we sought to elucidate the mechanisms by which 5-MTP regulates mitophagy via Nrf2 mediation.PATIENTS AND METHODS: We initially included 52 patients with sepsis, 25 of whom were diagnosed with AKI, and used metabolomics to analyze the serum levels of 5-MTP. We investigated the effects of exogenous 5-MTP on the kidneys of a mouse model with LPS-induced AKI. We explored the underlying mechanisms by assessing oxidative stress and mitophagy in the kidneys following the administration of different doses of 5-MTP to S-AKI mice. In addition, we used ML385 to inhibit Nrf2 expression and assessed mitophagy levels in kidney damage to investigate the specific mechanism by which 5-MTP mitigates S-AKI.RESULTS: The plasma 5-MTP levels were significantly higher in patients with S-AKI than in those with sepsis, showing a correlation with renal function. Administration of 5-MTP led to a decrease in inflammatory and oxidative stress reactions and stimulated the Nrf2 signaling pathway to alleviate kidney injury following the induction of sepsis. However, this protective effect was reversed by ML385. In S-AKI, 5-MTP therapy enhanced mitophagy and decreased kidney injury by upregulating the Nrf2/HO-1 pathway.CONCLUSION: Serum 5-MTP levels correlate with renal function and upregulate Nrf2 expression by activating the Nrf2 signaling pathway, thereby promoting renal tubular mitophagy and alleviating S-AKI.PMID:39618934 | PMC:PMC11608550 | DOI:10.2147/JIR.S474040

Rev Cardiovasc Med. 2024 Nov 7;25(11):395. doi: 10.31083/j.rcm2511395. eCollection 2024 Nov.ABSTRACTBACKGROUND: Coronary thrombosis events continue to be the leading cause of morbidity and mortality worldwide. Recently, emerging evidence has highlighted the role of gut microbiota in cardiovascular disease, but few studies have systematically investigated the gut microbiota variation associated with atherothrombosis.METHODS: We conducted multi-omics analysis (metagenomics sequencing and serum metabolomics) on 146 subjects from Peking Union Medical College Hospital-Coronary Artery Disease (PUMCH-CAD) cohort. We analyzed the key strains and metabolic pathways related to coronary artery disease (CAD) development, explored the bacterial functional pathway which contributes to atherothrombosis at strain level in depth. Single strain colonization procedures on germ free mice demonstrated the promotion of platelet activation and thrombotic phenotypes of the disordered gut microbiota.RESULTS: Gut microbiome and serum metabolome shifts were apparent in cases of CAD progression, Bacteroides spp. disturbed the development of CAD by participating in lipopolysaccharide (LPS), menaquinone and methanogenesis pathways. Particularly, coronary thrombosis is characterized by increased circulatory levels of L-tryptophan, which correlate with Bacteroides thetaiotaomicron that has enriched biosynthetic potential. In germ free mice we demonstrate that Bacteroides thetaiotaomicron colonization could induce thrombosis, aggravate platelet hyperreactivity and augment fecal levels of L-tryptophan.CONCLUSIONS: The disordered gut microbiota of CAD contributed to the occurrence and development of atherothrombosis. The key members of the bacterial and metabolic features may become biomarkers for predicting the cardiovascular thrombosis event. Targeting the microbial pathway may have the potential to reduce the incidence of cardiovascular disorders.CLINICAL TRIAL REGISTRATION: ChiCTR2000033897, https://www.chictr.org.cn/showproj.html?proj=55023.PMID:39618850 | PMC:PMC11607515 | DOI:10.31083/j.rcm2511395

Drug Des Devel Ther. 2024 Nov 27;18:5423-5444. doi: 10.2147/DDDT.S479014. eCollection 2024.ABSTRACTPURPOSE: Xiangqin Jiere Granules (XQJRG), a Chinese patent medicine used to treat acute fever in children caused by colds, seasonal flu, and coronavirus disease 2019 has been proven to have antipyretic and anti-inflammatory effects in young febrile rats. Fever is known to affect the host-gut microbiota crosstalk. However, the pharmacological mechanism of XQJRG in this regard remains unclear.METHODS: This study utilized a young febrile rat model previously reported by our team and extended the rat body temperature monitoring period following drug administration to explore the differences in efficacy between XQJRG and the commonly used pediatric antipyretic ibuprofen. Subsequently, the colonic contents of rats were analyzed using 16S rRNA gene sequencing and untargeted metabolomics. The short-chain fatty acid content was quantified using high-throughput targeted metabolomics. The expression of short-chain fatty acid receptors and pro-inflammatory genes in the colonic tissue was evaluated using quantitative real-time PCR, Western blot, and enzyme-linked immunosorbent assay.RESULTS: XQJRG showed a longer antipyretic duration than ibuprofen. XQJRG improved dysbiosis of the intestinal microbiota in young febrile rats, bringing its flora composition closer to that of normal rats. It significantly increased the relative abundance of s_Phascolarctobacterium_faecium and s_Roseburia_sp. related to the production of short-chain fatty acids (SCFAs), the contents of butyric acid and nonanoic acid and protein levels of SCFAs receptor GPR41. Moreover, XQJRG significantly increased the levels of metabolites with anti-inflammatory effects, reduced the contents of metabolites directly associated with fever, and decreased the levels of pro-inflammatory cytokines interleukin-1β and monocyte chemotactic protein-1 in the colon of young febrile rats to normal levels.CONCLUSION: XQJRG exhibited a more stable and persistent antipyretic effect in young febrile rats compared to ibuprofen. Its mechanism was at least partially attributed to regulating intestinal flora disorders, increasing anti-inflammatory metabolites, and inhibiting the production of inflammatory factors in young febrile rats.PMID:39618427 | PMC:PMC11608549 | DOI:10.2147/DDDT.S479014

Mol Nutr Food Res. 2024 Dec 1:e2400424. doi: 10.1002/mnfr.202400424. Online ahead of print.ABSTRACTSCOPE: Human milk (HM) is rich in bioactive compounds and essential nutrients. While research has focused on lipids, minerals, immune markers, microbiota, and oligosaccharides, specific metabolites are less studied. This study uses targeted metabolomics to identify and quantify metabolites in HM and explores the impact of perinatal and dietary factors on the metabolomic profile.METHODS AND RESULTS: In a cross-sectional study of 123 healthy lactating women, HM samples were collected up to 1 month postpartum and analyzed using the Biocrates MxP Quant 500 kit. Maternal and neonatal clinical, anthropometric, and nutritional data were collected. A total of 432 metabolites were quantified and categorized into 20 groups. The metabolomic profiles formed three distinct clusters, primarily driven by triglyceride concentration differences. Docosahexaenoic acid (DHA) levels were higher in HM from mothers with vaginal delivery compared to C-section births and differences in hexoses were found between exclusive and mixed-feeding practices. Maternal diets rich in lipids and animal proteins were associated with elevated amino acids, sphingolipids, and glycosyl-ceramides.CONCLUSION: The HM metabolome was grouped into three clusters influenced by delivery mode, lactation practices, and maternal diet. This comprehensive analysis opens new avenues to explore HM composition and offers valuable insights for future dietary interventions aimed at modulating HM.PMID:39617972 | DOI:10.1002/mnfr.202400424

Cell Commun Signal. 2024 Dec 2;22(1):574. doi: 10.1186/s12964-024-01928-9.ABSTRACTBACKGROUND: A key factor in the propagation of α-synuclein pathology is the compromised protein quality control system. Variations in membrane association and astrocytic uptake between different α-synuclein forms suggest differences in exocytosis or membrane cleavage, potentially impacting the secretome's influence on dopaminergic neurons. We aimed to understand differences in protein degradation mechanisms of astrocytes for both wild-type (WT) and mutant forms of α-synuclein, specifically during periods of reduced degradation efficiency. We also investigated α-synuclein release into the secretome and its effects on healthy dopaminergic neurons.METHODS: Cellular models used were rat primary astrocytes alongside hiPSC-derived astrocytes, whose impact on rat primary dopaminergic neurons and the human SH-SY5Y cell line was investigated. We examined the release and accumulation of α-synuclein resulting from impaired degradatory pathways, including matrix metalloprotease-MMP9, the ubiquitin proteasomal pathway-UPS, and the autophagy-lysosomal pathway-ALP, using immunocytochemical analysis and flow cytometry. Additionally, we explored the effect of astrocytic secretome on dopaminergic-neuronal survival, neurite collapse and function.RESULTS: At early stages, astrocytes were able to deal efficiently with monomeric α-synuclein (via UPS), and larger aggregates (through MMP9 and autophagy), clearing extracellular α-synuclein and maintaining neuronal health. However, extended exposure to extracellular monomeric and aggregated α-synuclein compromised their proteasomal activity, inhibiting MMP9 and destabilizing autophagy, transforming astrocytes from protectors to promoters of neurodegeneration. This study is the first to elucidate the astrocytes' preferred degradation pathways for both monomeric and aggregated forms of α-synuclein, along with the subsequent effects of these payloads on the cellular degradation machinery. The astrocytic transformation is characterized by α-synuclein expulsion, increased release of inflammatory cytokines, and diminished secretion of growth factors leading to dopaminergic neuronal apoptosis and dysfunction, particularly neurite collapse, intracellular Ca2+ response and vesicular dopamine release. The presence of phosphorylated and nitrated α-synuclein species in astrocytes also suggests their potential involvement in modifying both forms of the protein.CONCLUSION: The initial protective action of astrocytes in clearing and degrading extracellular α-synuclein is severely compromised at latter stages, leading to astrocytic dysfunction and impairing neuron-glia cross-talk. This study underscores the criticality of integrating astrocytes into treatment paradigms in synucleinopathies.PMID:39617881 | DOI:10.1186/s12964-024-01928-9

J Sep Sci. 2024 Dec;47(23):e70030. doi: 10.1002/jssc.70030.ABSTRACTShenhua Tablet (SHT), a Chinese herbal medicine comprising seven crude drugs, is utilized in the treatment of immunoglobulin A nephropathy (IgAN). However, due to its complex composition, the chemical constituents of SHT in vitro are still incompletely known, which has restricted the comprehensive development and utilization of SHT in clinical practice. In the present study based on ultra-high performance liquid chromatography-quadrupole-orbitrap-linear ion trap mass spectrometry (UHPLC-Q-Orbitrap-LTQ-MS) in data dependent acquisition mode, combining the accurate mass and structural information, the profiling and characterization of chemical constituents in SHT were carried out. The automated spectral matching (of experimental MS2 spectra against library spectra of mzCloud) method with a high mass accuracy (within 5 ppm) was used for the rapid identification of compounds. A total of 183 compounds, consisting of 64 flavonoids, 52 terpenoids, 37 organic acids, 6 phenylpropanoids, 5 phenols, and 19 other phytochemicals, were successfully characterized. In addition, the fragmentation pathways and characteristic fragments of some representative compounds were elucidated. The results offered clear insights into its chemical profile, thereby facilitating quality control and advancing pharmacological research.PMID:39617872 | DOI:10.1002/jssc.70030

Sci Rep. 2024 Dec 1;14(1):29839. doi: 10.1038/s41598-024-80169-9.ABSTRACTThe effectiveness of indirect Intravascular laser irradiation of blood (ILIB) is not fully understood. In this study, we provided a novel experiment that employs metabolomics to investigate the effects of ILIB in women. Twenty-eight volunteers underwent indirect ILIB and had their plasma collected before and after this procedure. The ILIB was applied at the radial artery for 30 min, using low-power photobiomodulation (660 nm), and a power output of 0.1 W. Plasma samples were extracted and analyzed using liquid chromatography-high-resolution mass spectrometry in an untargeted approach. Partial Least Squares Discriminant Analysis revealed 151 molecules with the Variable In Projection score of ≥ 1. From these, 26 were identified. After checking for molecules related to dietary intake, fasting, medication, or part of the human exposome, 15 were affected by ILIB. The abundances of Estradiol 17b-glucuronide 3-sulfate, CAR 14:3, PI 22:6/PGJ2, and CAR 12:1 significantly increased by ILIB, while AcylGlcADG 62:9, Tyrosyl-Glutamine, and CDP-DG 22:3/PGF1 had the contrary effect. ILIB was shown to modulate molecules from different chemical classes, although its impact on plasma metaboloma was minimal. Further research is warranted to fully elucidate the implications of these findings across various metabolic pathways, thus advancing the science surrounding ILIB.PMID:39617830 | DOI:10.1038/s41598-024-80169-9

Cell Death Dis. 2024 Dec 1;15(12):872. doi: 10.1038/s41419-024-07257-6.ABSTRACTThe metabolic reprogramming in high-grade serous ovarian carcinoma (HGSOC) affects the tumor stemness, which mediates tumor recurrence and progression. Knowledge of the stemness and metabolic characteristics of HGSOC is insufficient. Squalene epoxidase (SQLE), a key enzyme in cholesterol metabolism, was significantly upregulated in HGSOC samples with a fold change of about 4 in the RNA sequencing analysis. SQLE was positively related to peritoneal metastasis and poor prognosis of HGSOC patients. Functionally, SQLE drove cancer cell proliferation and inhibited apoptosis to accelerate HGSOC growth. SQLE was highly expressed in ALDH+CD133+ FACS-sorted cells derived from HGSOC cells and ovarian cancer stem cells (OCSCs)-enriched tumorspheres. SQLE overexpression resulted in enhanced CSC-like properties, including increased tumorsphere formation and stemness markers expression. In vivo, SQLE not only promoted cell line-derived xenografts growth but extended the OCSCs subpopulation of single-cell suspension. Moreover, non-targeted metabolomics profiling from UPLC-MS/MS system identified 90 differential metabolites responding to SQLE overexpression in HGSOC cells. Among them, the dysfunctional metabolisms of cholesterol and glutathione were involved in the maintenance of HGSOC stemness. Previous studies showed the alteration of N6-Methyladenosine (m6A) modification in HGSOC development. Herein, the m6A modification in the 3'UTR and CDS regions of SQLE mRNA was increased due to upregulated methyltransferases WTAP and downregulated demethylases FTO, which was recognized by m6A-binding proteins IGF2BP3, rather than IGF2BP1 or IGF2BP2, thereby stabilizing the SQLE mRNA. These results suggested that SQLE was a novel potential clinical marker for predicting the HGSOC development and prognosis, as well as a potential therapeutic target of HGSOC.PMID:39617776 | DOI:10.1038/s41419-024-07257-6

Chem Biodivers. 2024 Dec 1:e202402282. doi: 10.1002/cbdv.202402282. Online ahead of print.ABSTRACTThe UHPLC-MS/MS metabolomics approach was employed to profile and characterize multi-components in Halamphora sp. extracted with different solvents that contribute to quorum sensing inhibitory (QSI) activity. A total of 37 and 34 metabolites were tentatively identified from negative and positive ion modes, respectively. The metabolites have been assigned to various groups, including fatty acids, glycolipids, sterols, diazines, flavonoids, peptides, carotenoids, and pigments. ibitis study, a metabolomics apMultivariate data analysis showed that the QSI activity in the acetone extract was due to tumonoic acid A, terpeptin derivatives, pheophorbide A, hydroxyhexadeca-1,5-dien-3-ynoxy]propane-1,2-diol, L-methionyl-L-tyrosine, stearidonic, hexadecadienoic, tricosenoic, palmitic and linolenic acids. These metabolites were more concentrated and differed significantly in acetone extract compared to other extracts. Acetone extract displayed a cluster of nodulisporic acid and fucoxanthin through MS/MS-based molecular networking (MN) platform. The present study shows that the LCMS-based metabolomics and MN effectively identify QSI-active metabolites in Halamphora sp. extracts, which can be promoted as a natural antifoulant.PMID:39617725 | DOI:10.1002/cbdv.202402282

Angew Chem Int Ed Engl. 2024 Dec 1:e202420104. doi: 10.1002/anie.202420104. Online ahead of print.ABSTRACTLanostane-type triterpenoids are important bioactive secondary metabolites of mushrooms, though their biosynthetic study has been challenging due to scattered genes. Herein, the strategies of combining metabolomics and transcriptomics analyses, functional motif blast, and KEGG (Kyoto Encyclopedia of Genes and Genomes) annotation were used to discover three key post-modification enzymes involved in the biosynthesis of lanostanoids in the medicinal mushroom Antrodia camphorata. The cytochrome P450 enzyme AcCYP4 could generate a Δ7,9(11) diene structure and introduce a 15α-hydroxy group to the triterpene skeleton. The short-chain dehydrogenase AcSDR6 could regio- and stereo- selectively catalyze the dehydrogenation of 3β-OH to produce 3-keto triterpenoids, and the catalytic mechanisms were interpreted by crystal structure analysis. AcSMT1 could introduce the methyl group at C-24 to produce a unique 31-carbon triterpene skeleton. This work elucidated the major biosynthetic pathway of Antrodia lanostanoids in vitro, and the discovered enzymes could be used to synthesize a series of bioactive triterpenoids.PMID:39617723 | DOI:10.1002/anie.202420104

J Tradit Chin Med. 2024 Dec;44(6):1187-1193. doi: 10.19852/j.cnki.jtcm.2024.06.007.ABSTRACTOBJECTIVE: To investigate the effect of baijinpingchuan (, BJPC) on the asthma rat model and identify differential metabolites and disturbed metabolic pathways.METHODS: The rats were categorized into six groups: control, dexamethasone (DEX), ovalbumin (OVA), and low-, median-, and high-dose BJPC. The rats, except for the control group, were initially treated with OVA to develop the asthma model, which was then activated using DEX, OVA, and low-, median-, and high-dose BJPC. Enzyme-linked immunosorbent assay kit was used to detect the expression of interleukin (IL)-33, IL-25, thymic stromal lymphopoietin (TSLP), and transforming growth factor-beta 1 (TGF-β1). Hematoxylin and eosin staining were performed to observe the pathological condition of the lung. Untargeted serum metabonomic analysis was conducted to identify differential metabolites and disturbed metabolic pathways.RESULTS: High-dose BJPC significantly inhibited the expression of IL-33, IL-25, TSLP, and TGF-β1 (P < 0.0001). Further, high-dose BJPC improved inflammatory cell infiltration, which plays a similar role in asthma as DEX. OVA-induced and BJPC-treated rats were identified through 17 differential metabolites, especially cholic acid. Furthermore, primary bile acid biosynthesis was a significantly differential pathway in the mechanism of BJPC for treating asthma.CONCLUSIONS: BJPC plays an anti-inflammation role in asthma, which might be a promising therapy through mediating primary bile acid biosynthesis.PMID:39617704 | DOI:10.19852/j.cnki.jtcm.2024.06.007

J Tradit Chin Med. 2024 Dec;44(6):1127-1136. doi: 10.19852/j.cnki.jtcm.20240927.005.ABSTRACTOBJECTIVE: To investigate the mechanism of Qixuan Yijianing (,QYN) in minimizing cardiac injury in Graves' disease (GD) mice using microRNA (miRNA) sequencing analysis.METHODS: Female BALB/c mice were randomly divided into the modeling and control groups (CG). The modeling group was established with Ad-TSHR289. Following 10 weeks of successful modeling, the mice were randomly assigned to four groups: model (MG), methimazole (MMI), QYN low-dose (LD), and high-dose (HD). After four weeks of treatment, the heart rate, heart volume, and heart index were measured, and the levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (α-HBD), creatine kinase (CK), and creatine kinase MB isoenzyme (CK-MB) in the serum were detected using a biochemical analyzer. Hematoxylin-eosin and Masson staining were used to determine histological changes in cardiac tissue. The heart tissues in the CG, MG, and HD groups were selected, and miRNA sequencing was used to identify differentially expressed miRNAs. A bioinformatics database was used to predict the target genes of differential miRNAs, and Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted on the predicted target genes.RESULTS: As compared to the CG group, the MG group's heart rate, heart volume, heart index, AST, CK, CK-MB, LDH, α-HBD, myocardial fiber thickness, and collagen fiber significantly increased, all P < 0.01, while following QYN, these indicators improved in the HD group, all P < 0.01 or P < 0.05. Compared to the CG group, the MG group identified 151 differentially expressed miRNAs, with 42 miRNAs downregulated and 109 miRNAs upregulated; compared to the MG group, the HD group identified 70 differentially expressed miRNAs, 40 were downregulated, and 30 were upregulated. The GO functions of differential miRNA target genes are mostly enriched in cardiac development regulation, cardiac contraction control, heart rate regulation, and so on. The most enriched KEGG pathways include the mitogen-activated protein kinase, ErbB, Hippo, forkhead box protein O, and Wnt signaling pathways.CONCLUSION: QYN may protect the cardiac structure and function and minimize cardiac damage caused by GD by regulating relevant target genes and signaling pathways through miRNAs which include miR-206-3p, miR-122-5p, and miR-200a-3p.PMID:39617698 | DOI:10.19852/j.cnki.jtcm.20240927.005

J Environ Sci (China). 2025 Jun;152:313-327. doi: 10.1016/j.jes.2024.05.028. Epub 2024 May 22.ABSTRACTEnvironmental residues of the fungicide difenoconazole (DFZ) have been shown to pose a threat to mammals. However, the risk assessment of DFZ for cultured carp remains unclear. The aim of this study was to investigate the adverse effects of DFZ on carp liver and their molecular mechanisms by simulating the environmental contamination concentrations of DFZ. Our results showed that DFZ induced structural damage in the liver, including edema, vacuolation, and congestion. In addition, DFZ residues were detected in liver tissues. Mechanistically, DFZ causes mitochondrial dysfunction by promoting Ca2+ transfer from the endoplasmic reticulum (ER) to mitochondria via IP3R, leading to the onset of ROS burst and apoptosis, and the inhibition of Nrf2 antioxidant function by DFZ also results in uncontrolled ROS. Mitophagy was also activated intracellularly to counteract mitochondrial damage. Interestingly, treatment with 2-APB alleviated mitochondrial dysfunction, restored the mitochondrial membrane potential, and inhibited apoptosis by blocking the translocation of Ca2+ from the ER to the mitochondria. Metabolomic analysis revealed that DFZ disrupted energy metabolism in carp liver, whereas 2-APB reversed DFZ-induced metabolic alterations. In conclusion, the present study elucidates the threat of DFZ to carp liver and highlights the mechanism of damage, thereby helping to explain the impact of agriculture on the aquatic environment.PMID:39617555 | DOI:10.1016/j.jes.2024.05.028

Neurobiol Dis. 2024 Nov 29:106747. doi: 10.1016/j.nbd.2024.106747. Online ahead of print.ABSTRACTAlzheimer's disease (AD) affects more women than men. Although women live longer than men, it is not longevity alone, but other factors, including metabolic changes, that contribute to the higher risk of AD in women. Metabolic pathways have been implicated in AD progression, but studies to date examined targeted pathways, leaving many metabolites unmeasured. Sex is often a neglected biological variable, and most metabolomic studies were not designed to investigate sex differences in metabolomic profiles. Here, we performed untargeted metabolomic profiling of sera from male and female patients with mild cognitive impairment (MCI), a common precursor to AD, and matched controls. We discovered significant metabolic changes in individuals with MCI, and found several pathways that were strongly associated with sex. Peptide energy metabolism demonstrated sexual dimorphism. Lipid pathways exhibited the strongest differences between female and male MCI patients, including specific phosphatidylcholine lipids, lysophospholipids, long-chain fatty acids, and monoacylglycerols. 1-palmitoleoyl glycerol and 1-arachidonoyl glycerol were higher in female MCI subjects than in male MCI subjects with no differences between control males and females. Conversely, specific dicarboxylic fatty acids were lower in female MCI subjects than male MCI subjects. In cultured astrocytes, 1-arachidonoyl glycerol promoted phosphorylation of the transcriptional regulator sphingosine kinase 2, which was inhibited by the transient receptor potential vanilloid 1 receptor antagonists, as well as chromatin remodelling. Overall, we identified novel sex-specific metabolites in MCI patients that could serve as biomarkers of MCI in both sexes, help further define AD etiology, and reveal new potential prevention strategies for AD.PMID:39617329 | DOI:10.1016/j.nbd.2024.106747