PubMed

Aquat Toxicol. 2024 Feb 23;269:106879. doi: 10.1016/j.aquatox.2024.106879. Online ahead of print.ABSTRACTHow the particle size and concentration of microplastics impact their toxicity is largely unknown. Herein, the effects of polystyrene microplastics (1 μm, MPs) and nanoplastics (100 nm, NPs) exposed at 1 mg/L (L) and 10 mg/L (H), respectively, on the growth, histopathology, oxidative stress, gut microbiome, and metabolism of rare minnow (Gobiocypris rarus) were investigated by chemical analysis and multi-omics. MPs and NPs inhibited the growth, induced histopathological injury and aggravated oxidative stress markedly with contrasting significance of particle size and concentration. The composition of core gut microbiota changed dramatically especially for the MPs-H. Similarly, gut bacterial communities were reshaped by the MPs and NPs but only NPs-H decreased both richness and Shannon indexes significantly. Co-occurrence network analysis revealed that the potential keystone genera underwent great changes in exposed groups compared to the control. MPs-H increased the network complexity and the frequency of positive interactions which was opposite to other exposed groups. Moreover, the metabolomic profiles associated with amino acid, lipid, unsaturated fatty acid and hormone metabolism were disturbed significantly especially for MPs-H and NPs-H. In conclusion, the toxicity of MPs depends on both the particle size and concentration, and varies with the specific indicators as well.PMID:38422927 | DOI:10.1016/j.aquatox.2024.106879

Food Chem. 2024 Feb 6;445:138670. doi: 10.1016/j.foodchem.2024.138670. Online ahead of print.ABSTRACTHeat sterilization enhances the safety and shelf-life of braised chicken, but its impact on protein digestibility and the release of metabolites remains unclear. Here, braised chicken was sterilized at 80 °C (LS), 100 °C (MS), and 121 °C (HS) for 30 min. Protein digestibility was assessed by in vitro digestion, whereas the release of metabolites was analysed by UPLC-QTOF-MS spectroscopy. Results revealed that LS had higher gastrointestinal digestibility (88.86 %) than MS (81.79 %) and HS (78.13 %). Increased carbonyl content, turbidity, particle size, and hydrophobicity, along with decreased sulfhydryl content and solubility, indicated rising protein oxidation aggregation with higher sterilization temperatures, explaining reduced digestibility. 96 metabolites were identified. Compared to the control group, LS exhibited a statistically significant variation in the biosynthesis of unsaturated fatty acids, MS displayed a significant difference in purine metabolism, and HS showed a significant difference in primary bile acid biosynthesis. Thus, LS is a promising sterilization method.PMID:38422866 | DOI:10.1016/j.foodchem.2024.138670

Ecotoxicol Environ Saf. 2024 Feb 28;273:116099. doi: 10.1016/j.ecoenv.2024.116099. Online ahead of print.ABSTRACTSulfamethoxazole (SMZ) is a frequently detected antibiotic in the environment, and there is a growing concern about its potential toxic effects on aquatic organisms. sea cucumber (Apostichopus japonicas) is a benthic invertebrate whose gut acts as a primary immune defense and serves critical protective barrier. In this study, growth performance, histology, gut microbiota, and metabolomics analyses were performed to investigate the toxic response in the intestine of sea cucumber effects caused by SMZ stress for 56 d by evaluating with different concentrations of SMZ (0, 1.2×10-3, and 1.2 mg/L). The weight gain rate of sea cucumbers under SMZ stress showed significant decrease, indicating that the growth of sea cucumbers was hindered. Analysis of the intestinal morphological features indicated that SMZ stimulation resulted in atrophy of the sea cucumber gut. In the 1.2×10-3 mg/L concentration, the thickness of muscle and mucosal layers was reduced by 12.40% and 21.39%, while in the 1.2 mg/L concentration, the reductions were 35.08% and 26.98%. The abundance and diversity of sea cucumber intestinal bacteria decreased significantly (P < 0.05) under the influence of SMZ. Notably, the intestinal bacteria of sea cucumber became homogenized with the increase in SMZ concentration, and the relative abundance of Ralstonia reached 81.64% under the stress of 1.2 mg/L concentration. The SMZ stress significantly impacted host metabolism and disrupted balance, particularly in L-threonine, L-tyrosine, neuronic acid, piperine, and docosapentaenoic acid. SMZ leads to dysregulation of metabolites, resulting in growth inhibition and potential inflammatory responses that could adversely affect the normal activities of aquatic organisms. Further metabolic pathway enrichment analyses demonstrated that impaired biosynthesis of unsaturated fatty acids and aminoacyl-tRNA biosynthesis metabolic pathway were major reasons for SMZ stress-induced intestinal bacteria dysbiosis. This research aims to provide some theoretical evidence for the ecological hazard assessment of antibiotics in water.PMID:38422788 | DOI:10.1016/j.ecoenv.2024.116099

J Hazard Mater. 2024 Feb 28;469:133905. doi: 10.1016/j.jhazmat.2024.133905. Online ahead of print.ABSTRACTAs wellknown persistent contaminants, polycyclic aromatic hydrocarbons (PAHs) and heterocyclic polyaromatic hydrocarbons (Heterocyclic PAHs)'s fates in cryogenic environments are remains uncertain. Herein, strain S01 was identified as Pseudomonas fluorescens, a novel bacterium tolerant to low temperature and capable of degrading PAHs and heterocyclic PAHs. Strain S01 exhibited growth at 5-40 ℃ and degradation rate of mixed PAHs and heterocyclic PAHs reached 52% under low-temperature. Through comprehensive metabolomic, genomic, and transcriptomic analyses, we reconstructed the biodegradation pathway for PAHs and heterocyclic PAHs in S01 while investigating its response to low temperature. Further experiments involving deletion and replacement of methyl-accepting chemotaxis protein (MCP) confirmed its crucial role in enabling strain S01's adaptation to dual stress of low temperature and pollutants. Additionally, our analysis revealed that MCP was upregulated under cold stress which enhanced strain S01's motility capabilities leading to increased biofilm formation. The establishment of biofilm promoted preservation of distinct cellular membrane stability, thereby enhancing energy metabolism. Consequently, this led to heightened efficiency in pollutant degradation and improved cold resistance capabilities. Our findings provide a comprehensive understanding of the environmental fate of both PAHs and heterocyclic PAHs under low-temperature conditions while also shedding light on cold adaptation mechanism employed by strain S01.PMID:38422734 | DOI:10.1016/j.jhazmat.2024.133905

J Pharm Biomed Anal. 2024 Feb 17;242:116058. doi: 10.1016/j.jpba.2024.116058. Online ahead of print.ABSTRACTAIM: Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) granules is the extract preparation of EB, with clear curative effect and unclear mechanism. This study intends to systematically explore the specific mechanism of EB granules in the treatment of IS from the metabolic perspective.METHODS: The model of transient middle cerebral artery occlusion (tMCAO) in mice was established by the suture-occluded method. The therapeutic effect of EB granules on tMCAO mice was evaluated by behavioral evaluation, brain water content determination, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and levels of lactate dehydrogenase (LDH) and neuron specific enolase (NSE) in serum. In order to screen differential metabolites, non-targeted metabolomics technology was used to detect the metabolites in serum before and after administration. Univariate statistics, multivariate statistics and bioinformatics were used to analyze the changes of metabolites in serum of tMCAO mice. The possible related mechanism of EB granules in treating IS was screened by pathway enrichment analysis, and the preliminary verification was carried out at animal level by enzyme linked immunosorbent assay (ELISA) and western blot (WB).RESULTS: EB granules could significantly improve behavior of tMCAO mice, reduce brain water content and cerebral infarction volume, improve morphology of brain tissue, reduce the levels of LDH and NSE in serum. A total of 232 differential metabolites were screened, which were mainly enriched in many biological processes such as sphingolipid metabolism. The differential metabolite S1P and its receptors S1PR1 and S1PR2 in sphingolipid metabolism were verified. The results showed that the level of S1P in brain tissue increased and the protein expression of S1PR1 decreased significantly after modeling, and reversed after administration, but there was no significant difference in the protein expression of S1PR2.CONCLUSION: The therapeutic effects of EB granules may be related to affecting sphingolipid metabolism through regulating S1P/S1PR1.PMID:38422673 | DOI:10.1016/j.jpba.2024.116058

J Pharm Biomed Anal. 2024 Feb 17;242:116059. doi: 10.1016/j.jpba.2024.116059. Online ahead of print.ABSTRACTCentral precocious puberty (CPP) is a prevalent endocrine disorder that primarily affects children, specifically females, and is associated with various physical and psychological complications. Although Kangzao granules (KZG) are efficacious in managing CPP, the underlying mechanisms remain unclear. Therefore, this study aimed to elucidate the therapeutic mechanisms of KZG using network pharmacology, molecular docking, pharmacodynamics, and pathway validation. A putative compound-target-pathway network was constructed using Cytoscape, before KEGG and Gene Ontology enrichment analyses were conducted. Moreover, molecular docking was performed using AutoDockTools. Quality control of the 10 key components of KZG was carried out using UHPLC-ESI/LTQ-Orbitrap-MS/MS, and hypothalamic lipids were analyzed using UHPLC-Q-Exactive Orbitrap MS/MS. In total, 87 bioactive compounds that targeting 110 core proteins to alleviate CPP were identified in KZG. Lipidomic analysis revealed 18 differential lipids among the CPP, KZG, and control groups, wherein fatty acids were significantly reduced in the model group; however, these changes were effectively counteracted by KZG treatment. Molecular docking analysis revealed a strong binding affinity between flavonoids and RAC-alpha serine/threonine-protein kinase (AKT) when docked into the crystal structure. Moreover, a substantial disruption in lipid metabolism was observed in the model group; however, treatment with KZG efficiently reversed these alterations. Furthermore, the phosphoinositide 3-kinase/AKT signaling pathway was identified as a pivotal regulator of hypothalamic lipid metabolism regulator. Overall, this study highlights the effectiveness of a multidisciplinary approach that combines network pharmacology, lipidomics, molecular docking, and experimental validation in the elucidation of the therapeutic mechanisms of KZG in CPP treatment.PMID:38422672 | DOI:10.1016/j.jpba.2024.116059

J Pharm Biomed Anal. 2024 Feb 15;242:116034. doi: 10.1016/j.jpba.2024.116034. Online ahead of print.ABSTRACTT-cells play a significant role in the development of autoimmune diseases. The CD28-B7 costimulatory pathway is crucial for activating T-cells, and blocking this pathway is essential for treating autoimmune diseases. Therapeutic antibodies and fusion proteins that target costimulatory molecules like CD80, CD86, CTLA-4, and CD28 have been developed to explore the costimulation process and as targeted treatments. To advance our understanding of costimulation in autoimmunity and the inhibition of the costimulatory pathway, it is crucial to have an accurate, precise, and direct method for detecting and quantifying the soluble form of these molecules in body fluids and various biological systems. Herein, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying the four costimulatory proteins depending on the signature peptides derived from the soluble isoform of these proteins in multiple reaction monitoring (MRM) mode. The method was validated using the US FDA guidelines. The LOQ was determined as ∼0.5 nM for the four analytes, with quantification extended to 20 nM with a correlation coefficient of R2>0.998. The developed MRM method was used to analyze on-bead digested protein mixtures to establish a competitive assay for the CD28-B7 costimulatory pathway using CTLA4-Ig (Abatacept ™) as an FDA-approved drug for rheumatoid arthritis. The IC50 was determined to be 2.99 and 159.8 nM for sCD80 and sCD86, respectively. A straightforward MRM-based competitive assay will advance the knowledge about the costimulatory role in autoimmunity and the autoimmune therapeutic drug discovery, with the need for broad application on different in vitro and in vivo models to discover new targeted inhibitors.PMID:38422671 | DOI:10.1016/j.jpba.2024.116034

Biomed Pharmacother. 2024 Feb 28;173:116305. doi: 10.1016/j.biopha.2024.116305. Online ahead of print.ABSTRACTBACKGROUND: Through bioinformatics analysis, this study explores the interactions and biological pathways involving metabolomic products in patients diagnosed with coronary heart disease (CHD).METHODS: A comprehensive search for relevant studies focusing on metabolomics analysis in CHD patients was conducted across databases including CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, Nature, Web of Science, Springer, and Science Direct. Metabolites reported in the literature underwent statistical analysis and summarization, with the identification of differential metabolites. The pathways associated with these metabolites were examined using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Molecular annotation of metabolites and their relationships with enzymes or transporters were elucidated through analysis with the Human Metabolome Database (HMDB). Visual representation of the properties related to these metabolites was achieved using Metabolomics Pathway Analysis (metPA).RESULTS: A total of 13 literatures satisfying the criteria for enrollment were included. A total of 91 metabolites related to CHD were preliminarily screened, and 87 effective metabolites were obtained after the unrecognized metabolites were excluded. A total of 45 pathways were involved. Through the topology analysis (TPA) of pathways, their influence values were calculated, and 13 major metabolic pathways were selected. The pathways such as Phenylalanine, tyrosine, and tryptophan biosynthesis, Citrate cycle (TCA cycle), Glyoxylate and dicarboxylate metabolism, and Glycine, serine, and threonine metabolism primarily involved the regulation of processes and metabolites related to inflammation, oxidative stress, one-carbon metabolism, energy metabolism, lipid metabolism, immune regulation, and nitric oxide expression.CONCLUSION: Multiple pathways, including Phenylalanine, tyrosine, and tryptophan biosynthesis, Citrate cycle (TCA cycle), Glyoxylate and dicarboxylate metabolism, and Glycine, serine, and threonine metabolism, were involved in the occurrence of CHD. The occurrence of CHD is primarily associated with the regulation of processes and metabolites related to inflammation, oxidative stress, one-carbon metabolism, energy metabolism, lipid metabolism, immune regulation, and nitric oxide expression.PMID:38422653 | DOI:10.1016/j.biopha.2024.116305

Phytomedicine. 2024 Feb 5;126:155422. doi: 10.1016/j.phymed.2024.155422. Online ahead of print.ABSTRACTBACKGROUND: Prenatal stress (PS) can cause cognitive disorder and a range of psychological illnesses, including anxiety and depression. Icariin (ICA) has shown promising effects in improving PS-induced depressive behaviour. However, its mechanism of action remains unclear.PURPOSE: This study was performed to reveal the key targets, metabolites and gut microbiota for ICA in improving depressive behaviour in PS rat pups.METHODS: A prenatal restraint stress animal model was established for Sprague-Dawley (SD) rats in late pregnancy. Male pups were randomly divided into six groups: no stress group (NS), PS group, PS + saline group (PS_S), PS + high-dose ICA group (ICAH, 80 mg/kg*day), PS + low-dose ICA group (ICAL, 40 mg/kg*day) and PS + fluoxetine group (FLU, 10 mg/kg*day). The depressive behaviour of each group of rat pups was evaluated using open field test, forced swimming test and sucrose preference test. Different metabolites were identified using untargeted metabolomics of serum and faeces, and metabolic pathways were analyzed through MetaboAnalyst. Targets for ICA acting on depression were determined after network pharmacology was applied. An integrated network of network pharmacology and metabolomics were constructed using Cytoscape software, and molecular docking were performed to verify the interactions between ICA and key targets. Finally, gut microbiota of rat pups in each group were analyzed after 16S rDNA sequencing.RESULTS: PS could cause rat pups to exhibit depressive behaviour, and ICA could significantly improve this depressive behaviour. A total of 49 differential metabolites were found in serum and 23 differential metabolites were found in faeces, and 24 metabolites in serum and 6 metabolites in faeces could be reversed following ICA administration. Integrated analysis focused on five key targets (i.e. adenosyl homocysteinase; medium-chain specific acyl-CoA dehydrogenase, mitochondrial; thymidine phosphorylase; cGMP-specific 3',5'-cyclic phosphodiesterase and xanthine dehydrogenase/oxidase) and three metabolites (i.e. palmitoylcarnitine, methionine and hypoxanthine). Molecular docking indicated that ICA combined well with key targets. Gut microbiota analysis showed that g_Bacteroides, f_Bacteroidaceae and s_Lactobacillus reuteri were required for ICA to improve depressive behaviour.CONCLUSION: In this study, the antidepressant mechanism of ICA was clarified with a strategy of integrating metabolomics, network pharmacology and gut microbiota. ICA has a good effect on improving metabolism and increasing the abundance of probiotics in the intestine. The present research provided new insights into the anti-depressant mechanism of ICA.PMID:38422651 | DOI:10.1016/j.phymed.2024.155422

Food Chem. 2024 Feb 27;446:138886. doi: 10.1016/j.foodchem.2024.138886. Online ahead of print.ABSTRACTPickled radish is a traditional fermented food with a unique flavor after long-term preservation. This study analyzed the organoleptic and chemical characteristics of pickled radish from different years to investigate quality changes during pickling. The results showed that the sourness, saltiness, and aftertaste-bitterness increased after pickling, and bitterness and astringency decreased. The levels of free amino acids, soluble sugars, total phenols, and total flavonoids initially decreased during pickling but increased with prolonged pickling. The diversity of organic acids also increased over time. Through non-targeted metabolomics analysis, 349 differential metabolites causing metabolic changes were identified to affect the quality formation of pickled radish mainly through amino acid metabolism, phenylpropane biosynthesis and lipid metabolism. Correlation analysis showed that L*, soluble sugars, lactic acid, and acetic acid were strongly associated with taste quality. These findings provide a theoretical basis for standardizing and scaling up traditional pickled radish production.PMID:38422641 | DOI:10.1016/j.foodchem.2024.138886

Food Chem. 2024 Feb 17;446:138769. doi: 10.1016/j.foodchem.2024.138769. Online ahead of print.ABSTRACTChaya (Cnidoscolus chayamansa) leaves are known for their strong umami taste and widespread use as a dried seasoning. This study aimed to assess the impact of different drying methods [freeze drying (FD), vacuum drying, oven drying at 50 °C and 120 °C (OD120) and pan roasting (PR)] on the metabolome using mass spectrometry, umami intensity, and antioxidant properties of chaya leaves. The predominant volatile compound among all samples, 3-methylbutanal, exhibited the highest relative odor activity value (rOAV), imparting a malt-like odor, while hexanal (green grass-like odor) and 2-methylbutanal (coffee-like odor) are the second highest rOAV in the FD and PR samples, respectively. OD120 and PR samples possessed the highest levels of umami-tasting amino acids and 5'-ribonucleotides as well as the most intense umami taste, whereas FD samples exhibited the highest antioxidant capacity. These findings enhance our understanding of the aroma characteristics, umami taste, and antioxidant potential of processed chaya leaves.PMID:38422636 | DOI:10.1016/j.foodchem.2024.138769

J Transl Med. 2024 Feb 29;22(1):214. doi: 10.1186/s12967-024-05029-6.ABSTRACTBACKGROUND: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) variant syndrome (VS) exhibit a complex overlap of AIH features with PBC, leading to poorer prognoses than those with PBC or AIH alone. The biomarkers associated with drug response and potential molecular mechanisms in this syndrome have not been fully elucidated.METHODS: Whole-transcriptome sequencing was employed to discern differentially expressed (DE) RNAs within good responders (GR) and poor responders (PR) among patients with PBC/AIH VS. Subsequent gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted for the identified DE RNAs. Plasma metabolomics was employed to delineate the metabolic profiles distinguishing PR and GR groups. The quantification of immune cell profiles and associated cytokines was achieved through flow cytometry and immunoassay technology. Uni- and multivariable logistic regression analyses were conducted to construct a predictive model for insufficient biochemical response. The performance of the model was assessed by computing the area under the receiver operating characteristic (AUC) curve, sensitivity, and specificity.FINDINGS: The analysis identified 224 differentially expressed (DE) mRNAs, 189 DE long non-coding RNAs, 39 DE circular RNAs, and 63 DE microRNAs. Functional pathway analysis revealed enrichment in lipid metabolic pathways and immune response. Metabolomics disclosed dysregulated lipid metabolism and identified PC (18:2/18:2) and PC (16:0/20:3) as predictors. CD4+ T helper (Th) cells, including Th2 cells and regulatory T cells (Tregs), were upregulated in the GR group. Pro-inflammatory cytokines (IFN-γ, TNF-α, IL-9, and IL-17) were downregulated in the GR group, while anti-inflammatory cytokines (IL-10, IL-4, IL-5, and IL-22) were elevated. Regulatory networks were constructed, identifying CACNA1H and ACAA1 as target genes. A predictive model based on these indicators demonstrated an AUC of 0.986 in the primary cohort and an AUC of 0.940 in the validation cohort for predicting complete biochemical response.CONCLUSION: A combined model integrating genomic, metabolic, and cytokinomic features demonstrated high accuracy in predicting insufficient biochemical response in patients with PBC/AIH VS. Early recognition of individuals at elevated risk for insufficient response allows for the prompt initiation of additional treatments.PMID:38424613 | DOI:10.1186/s12967-024-05029-6

J Transl Med. 2024 Feb 29;22(1):219. doi: 10.1186/s12967-024-05022-z.ABSTRACTBACKGROUND: The rapid emergence and global dissemination of the Omicron variant of SARS-CoV-2 have posed formidable challenges in public health. This scenario underscores the urgent need for an enhanced understanding of Omicron's pathophysiological mechanisms to guide clinical management and shape public health strategies. Our study is aimed at deciphering the intricate molecular mechanisms underlying Omicron infections, particularly focusing on the identification of specific biomarkers.METHODS: This investigation employed a robust and systematic approach, initially encompassing 15 Omicron-infected patients and an equal number of healthy controls, followed by a validation cohort of 20 individuals per group. The study's methodological framework included a comprehensive multi-omics analysis that integrated proteomics and metabolomics, augmented by extensive bioinformatics. Proteomic exploration was conducted via an advanced Ultra-High-Performance Liquid Chromatography (UHPLC) system linked with mass spectrometry. Concurrently, metabolomic profiling was executed using an Ultra-Performance Liquid Chromatography (UPLC) system. The bioinformatics component, fundamental to this research, entailed an exhaustive analysis of protein-protein interactions, pathway enrichment, and metabolic network dynamics, utilizing state-of-the-art tools such as the STRING database and Cytoscape software, ensuring a holistic interpretation of the data.RESULTS: Our proteomic inquiry identified eight notably dysregulated proteins (THBS1, ACTN1, ACTC1, POTEF, ACTB, TPM4, VCL, ICAM1) in individuals infected with the Omicron variant. These proteins play critical roles in essential physiological processes, especially within the coagulation cascade and hemostatic mechanisms, suggesting their significant involvement in the pathogenesis of Omicron infection. Complementing these proteomic insights, metabolomic analysis discerned 146 differentially expressed metabolites, intricately associated with pivotal metabolic pathways such as tryptophan metabolism, retinol metabolism, and steroid hormone biosynthesis. This comprehensive metabolic profiling sheds light on the systemic implications of Omicron infection, underscoring profound alterations in metabolic equilibrium.CONCLUSIONS: This study substantially enriches our comprehension of the physiological ramifications induced by the Omicron variant, with a particular emphasis on the pivotal roles of coagulation and platelet pathways in disease pathogenesis. The discovery of these specific biomarkers illuminates their potential as critical targets for diagnostic and therapeutic strategies, providing invaluable insights for the development of tailored treatments and enhancing patient care in the dynamic context of the ongoing pandemic.PMID:38424541 | DOI:10.1186/s12967-024-05022-z

Metabolomics. 2024 Feb 29;20(2):32. doi: 10.1007/s11306-023-02072-0.ABSTRACTINTRODUCTION: The microbial community plays a crucial role in the pathological microenvironment. However, the structure of the microbial community within endometriotic lesions and its impact on the microenvironment is still limited.METHODS: All 55 tissue samples, including ovarian ectopic (OEMs) and normal (NE) endometrium, were subjected to 16S rRNA sequencing, metabolomic and proteomic analysis.RESULTS: We found the abundance of Tuzzerella is significantly lower in OEMs compared to NE tissue (p < 0.01). We selected samples from these two groups that exhibited the most pronounced difference in Tuzzerella abundance for further metabolomic and proteomic analysis. Our findings indicated that endometriotic lesions were associated with a decrease in L-Glutamine levels. However, proteomic analysis revealed a significant upregulation of proteins related to the complement pathway, including C3, C7, C1S, CLU, and A2M. Subsequent metabolic and protein correlation predictions demonstrated a negative regulation between L-Glutamine and C7. In vitro experiments further confirmed that high concentrations of Glutamine significantly inhibit C7 protein expression. Additionally, immune cell infiltration analysis, multiplex immunofluorescence, and multifactorial testing demonstrated a positive correlation between C7 expression and the infiltration of regulatory T cells (Tregs) in ectopic lesions, while L-Glutamine was found to negatively regulate the expression of chemotactic factors for Tregs.CONCLUSION: In this study, we found a clear multi-omics pathway alteration, "Tuzzerella (microbe)-L-Glutamine (metabolite)-C7 (protein)," which affects the infiltration of Tregs in endometriotic lesions. Our findings provide insights into endometriosis classification and personalized treatment strategies based on microbial structures.PMID:38424274 | DOI:10.1007/s11306-023-02072-0

Nat Cell Biol. 2024 Feb 29. doi: 10.1038/s41556-024-01360-8. Online ahead of print.ABSTRACTFerroptosis, an intricately regulated form of cell death characterized by uncontrolled lipid peroxidation, has garnered substantial interest since this term was first coined in 2012. Recent years have witnessed remarkable progress in elucidating the detailed molecular mechanisms that govern ferroptosis induction and defence, with particular emphasis on the roles of heterogeneity and plasticity. In this Review, we discuss the molecular ecosystem of ferroptosis, with implications that may inform and enable safe and effective therapeutic strategies across a broad spectrum of diseases.PMID:38424270 | DOI:10.1038/s41556-024-01360-8

Annu Rev Plant Biol. 2024 Feb 29. doi: 10.1146/annurev-arplant-060223-013842. Online ahead of print.ABSTRACTPlant specialized metabolites (PSMs) are variably distributed across taxa, tissues, and ecological contexts; this variability has inspired many theories about PSM function, which to-date remain poorly tested because predictions have outpaced the available data. Advances in mass spectrometry-based metabolomics have enabled unbiased PSM profiling, and molecular biology techniques have produced PSM-free plants; the combination of these methods has accelerated our understanding of the complex ecological roles that PSMs play in plants. Synthetic biology techniques and workflows are producing high-value, structurally complex PSMs in quantities and purities sufficient for both medicinal and functional studies. These workflows enable the reengineering of PSM transport, externalization, structural diversity, and production in novel taxa, facilitating rigorous tests of long-standing theoretical predictions about why plants produce so many different PSMs in particular tissues and ecological contexts. Plants use their chemical prowess to solve ecological challenges, and synthetic biology workflows are accelerating our understanding of these evolved functions. Expected final online publication date for the Annual Review of Plant Biology, Volume 75 is May 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.PMID:38424065 | DOI:10.1146/annurev-arplant-060223-013842

Annu Rev Anal Chem (Palo Alto Calif). 2024 Feb 29. doi: 10.1146/annurev-anchem-061522-041154. Online ahead of print.ABSTRACTIn this review, we discuss the cutting-edge developments in mass spectrometry proteomics and metabolomics that have brought improvements for the identification of new disease-based biomarkers. A special focus is placed on psychiatric disorders, for example, schizophrenia, because they are considered to be not a single disease entity but rather a spectrum of disorders with many overlapping symptoms. This review includes descriptions of various types of commonly used mass spectrometry platforms for biomarker research, as well as complementary techniques to maximize data coverage, reduce sample heterogeneity, and work around potentially confounding factors. Finally, we summarize the different statistical methods that can be used for improving data quality to aid in reliability and interpretation of proteomics findings, as well as to enhance their translatability into clinical use and generalizability to new data sets. Expected final online publication date for the Annual Review of Analytical Chemistry, Volume 17 is May 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.PMID:38424029 | DOI:10.1146/annurev-anchem-061522-041154

BMJ Open Respir Res. 2024 Feb 29;11(1):e001762. doi: 10.1136/bmjresp-2023-001762.ABSTRACTINTRODUCTION: The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting COVID-19. Improved therapeutic strategies are urgently needed to better intervene particularly in severe cases of the disease. They should aim at controlling the hyperinflammatory state generated on infection, reducing lung tissue pathology and inhibiting viral replication. Previous research has pointed to a possible role for the chaperone HSP90 in SARS-CoV-2 replication and COVID-19 pathogenesis. Pharmacological intervention through HSP90 inhibitors was shown to be beneficial in the treatment of inflammatory diseases, infections and reducing replication of diverse viruses.METHODS: In this study, we investigated the effects of the potent HSP90 inhibitor Ganetespib (STA-9090) in vitro on alveolar epithelial cells and alveolar macrophages to characterise its effects on cell activation and viral replication. Additionally, the Syrian hamster animal model was used to evaluate its efficacy in controlling systemic inflammation and viral burden after infection.RESULTS: In vitro, STA-9090 reduced viral replication on alveolar epithelial cells in a dose-dependent manner and lowered significantly the expression of proinflammatory genes, in both alveolar epithelial cells and alveolar macrophages. In vivo, although no reduction in viral load was observed, administration of STA-9090 led to an overall improvement of the clinical condition of infected animals, with reduced oedema formation and lung tissue pathology.CONCLUSION: Altogether, we show that HSP90 inhibition could serve as a potential treatment option for moderate and severe cases of COVID-19.PMID:38423952 | DOI:10.1136/bmjresp-2023-001762

Int J Biol Macromol. 2024 Feb 5:129856. doi: 10.1016/j.ijbiomac.2024.129856. Online ahead of print.ABSTRACTIn this study, a novel polysaccharide, AAP-2S, was extracted from Auricularia auricula, and the anti-glycosylation effect of AAP-2S and its underlying mechanisms were investigated using an in vitro BSA-fructose model and a cellular model. The results demonstrated the inhibiting formation of advanced glycation end products (AGEs) in vitro by AAP-2S. Concurrently, it attenuated oxidative damage to proteins in the model, preserved protein sulfhydryl groups from oxidation, reduced protein carbonylation, prevented structural alterations in proteins, and decreased the formation of β-crosslinked structures. Furthermore, AAP-2S demonstrated metal-chelating capabilities. GC-MS/MS-based metabolomics were employed to analyze changes in metabolic profiles induced by AAP-2S in a CML-induced HK-2 cell model. Mechanistic investigations revealed that AAP-2S could mitigate glycosylation and ameliorate cell fibrosis by modulating the RAGE/TGF-β/NOX4 pathway. This study provides a foundational framework for further exploration of Auricularia auricular polysaccharide as a natural anti-AGEs agent, paving the way for its potential development and application as a food additive.PMID:38423908 | DOI:10.1016/j.ijbiomac.2024.129856

Sci Bull (Beijing). 2024 Jan 2:S2095-9273(23)00939-8. doi: 10.1016/j.scib.2023.12.053. Online ahead of print.ABSTRACTDiabetic retinopathy (DR) is the leading cause of blindness among the working-age population. Although controlling blood glucose levels effectively reduces the incidence and development of DR to less than 50%, there are currently no diagnostic biomarkers or effective treatments for DR development in glucose-well-controlled diabetic patients (GW-DR). In this study, we established a prospective GW-DR cohort by strictly adhering to glycemic control guidelines and maintaining regular retinal examinations over a median 2-year follow-up period. The discovery cohort encompassed 71 individuals selected from a pool of 292 recruited diabetic patients at baseline, all of whom consistently maintained hemoglobin A1c (HbA1c) levels below 7% without experiencing hypoglycemia. Within this cohort of 71 individuals, 21 subsequently experienced new-onset GW-DR, resulting in an incidence rate of 29.6%. In the validation cohort, we also observed a significant GW-DR incidence rate of 17.9%. Employing targeted metabolomics, we investigated the metabolic characteristics of serum in GW-DR, revealing a significant association between lower levels of ethanolamine and GW-DR risk. This association was corroborated in the validation cohort, exhibiting superior diagnostic performance in distinguishing GW-DR from diabetes compared to the conventional risk factor HbA1c, with AUCs of 0.954 versus 0.506 and 0.906 versus 0.521 in the discovery and validation cohorts, respectively. Furthermore, in a streptozotocin (STZ)-induced diabetic rat model, ethanolamine attenuated diabetic retinal inflammation, accompanied by suppression of microglial diacylglycerol (DAG)-dependent protein kinase C (PKC) pathway activation. In conclusion, we propose that ethanolamine is a potential biomarker and represents a viable biomarker-based therapeutic option for GW-DR.PMID:38423871 | DOI:10.1016/j.scib.2023.12.053