PubMed

Diabetologia. 2024 May 21. doi: 10.1007/s00125-024-06169-6. Online ahead of print.ABSTRACTAIMS/HYPOTHESIS: Many studies have examined the relationship between plasma metabolites and type 2 diabetes progression, but few have explored saliva and multi-fluid metabolites.METHODS: We used LC/MS to measure plasma (n=1051) and saliva (n=635) metabolites among Puerto Rican adults from the San Juan Overweight Adults Longitudinal Study. We used elastic net regression to identify plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting baseline HOMA-IR in a training set (n=509) and validated these scores in a testing set (n=340). We used multivariable Cox proportional hazards models to estimate HRs for the association of baseline metabolomic scores predicting insulin resistance with incident type 2 diabetes (n=54) and prediabetes (characterised by impaired glucose tolerance, impaired fasting glucose and/or high HbA1c) (n=130) at 3 years, along with regression from prediabetes to normoglycaemia (n=122), adjusting for traditional diabetes-related risk factors.RESULTS: Plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance included highly weighted metabolites from fructose, tyrosine, lipid and amino acid metabolism. Each SD increase in the plasma (HR 1.99 [95% CI 1.18, 3.38]; p=0.01) and multi-fluid (1.80 [1.06, 3.07]; p=0.03) metabolomic scores was associated with higher risk of type 2 diabetes. The saliva metabolomic score was associated with incident prediabetes (1.48 [1.17, 1.86]; p=0.001). All three metabolomic scores were significantly associated with lower likelihood of regressing from prediabetes to normoglycaemia in models adjusting for adiposity (HRs 0.72 for plasma, 0.78 for saliva and 0.72 for multi-fluid), but associations were attenuated when adjusting for lipid and glycaemic measures.CONCLUSIONS/INTERPRETATION: The plasma metabolomic score predicting insulin resistance was more strongly associated with incident type 2 diabetes than the saliva metabolomic score. Only the saliva metabolomic score was associated with incident prediabetes.PMID:38772919 | DOI:10.1007/s00125-024-06169-6

J Sep Sci. 2024 May;47(9-10):e2400155. doi: 10.1002/jssc.202400155.ABSTRACTRapid evaporative ionization mass spectrometry (REIMS) is a relatively recent MS technique explored in many application fields, demonstrating high versatility in the detection of a wide range of chemicals, from small molecules (phenols, amino acids, di- and tripeptides, organic acids, and sugars) to larger biomolecules, that is, phospholipids and triacylglycerols. Different sampling devices were used depending on the analyzed matrix (liquid or solid), resulting in distinct performances in terms of automation, reproducibility, and sensitivity. The absence of laborious and time-consuming sample preparation procedures and chromatographic separations was highlighted as a major advantage compared to chromatographic methods. REIMS was successfully used to achieve a comprehensive sample profiling according to a metabolomics untargeted analysis. Moreover, when a multitude of samples were available, the combination with chemometrics allowed rapid sample differentiation and the identification of discriminant features. The present review aims to provide a survey of literature reports based on the use of such analytical technology, highlighting its mode of operation in different application areas, ranging from clinical research, mostly focused on cancer diagnosis for the accurate identification of tumor margins, to the agri-food sector aiming at the safeguard of food quality and security.PMID:38772742 | DOI:10.1002/jssc.202400155

Ann N Y Acad Sci. 2024 May 21. doi: 10.1111/nyas.15147. Online ahead of print.ABSTRACTAmyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. The immunosuppressive functions of regulatory T lymphocytes (Tregs) are impaired in ALS, and correlate to disease progression. The phase 2a IMODALS trial reported an increase in Treg number in ALS patients following the administration of low-dose (ld) interleukin-2 (IL-2). We propose a pharmacometabolomics approach to decipher metabolic modifications occurring in patients treated with ld-IL-2 and its relationship with Treg response. Blood metabolomic profiles were determined on days D1, D64, and D85 from patients receiving 2 MIU of IL-2 (n = 12) and patients receiving a placebo (n = 12). We discriminated the three time points for the treatment group (average error rate of 42%). Among the important metabolites, kynurenine increased between D1 and D64, followed by a reduction at D85. The percentage increase of Treg number from D1 to D64, as predicted by the metabolome at D1, was highly correlated with the observed value. This study provided a proof of concept for metabolic characterization of the effect of ld-IL-2 in ALS. These data could present advances toward a personalized medicine approach and present pharmacometabolomics as a key tool to complement genomic and transcriptional data for drug characterization, leading to systems pharmacology.PMID:38771698 | DOI:10.1111/nyas.15147

Plant Physiol. 2024 May 21:kiae287. doi: 10.1093/plphys/kiae287. Online ahead of print.ABSTRACTLignin is a phenolic polymer in plants that rigidifies the cell walls of water-conducting tracheary elements and support-providing fibers and stone cells. Different mechanisms have been suggested for the transport of lignin precursors to the site of lignification in the cell wall. Extracellular vesicle (EV)-enriched samples isolated from a lignin-forming cell suspension culture of Norway spruce (Picea abies L. Karst.) contained both phenolic metabolites and enzymes related to lignin biosynthesis. Metabolomic analysis revealed mono-, di- and oligolignols in the EV isolates, as well as carbohydrates and amino acids. In addition, salicylic acid (SA) and some proteins involved in SA signaling were detected in the EV-enriched samples. A proteomic analysis detected several laccases, peroxidases, β-glucosidases, putative dirigent proteins, and cell wall-modifying enzymes such as glycosyl hydrolases, transglucosylase/hydrolases, and expansins in EVs. Our findings suggest that EVs are involved in transporting enzymes required for lignin polymerization in Norway spruce, and that radical coupling of monolignols can occur in these vesicles.PMID:38771246 | DOI:10.1093/plphys/kiae287

Clin Transl Sci. 2024 May;17(5):e13834. doi: 10.1111/cts.13834.ABSTRACTPioglitazone is class of thiazolidinediones that activates peroxisome proliferator-activated receptors (PPARs) in adipocytes to improve glucose metabolism and insulin sensitivity and has been used as a treatment for type 2 diabetes. However, the underlying mechanisms of associated pioglitazone-induced effects remain unclear. Our study aimed to investigate endogenous metabolite alterations associated with pioglitazone administration in healthy male subjects using an untargeted metabolomics approach. All subjects received 30 mg of pioglitazone once daily in the assigned sequence and period. Urine samples were collected before pioglitazone administration and for 24 h after 7 days of administration. A total of 1465 compounds were detected and filtered using a coefficient of variance below 30% and 108 metabolites were significantly altered upon pioglitazone administration via multivariate statistical analysis. Fourteen significant metabolites were identified using authentic standards and public libraries. Additionally, pathway analysis revealed that metabolites from purine and beta-alanine metabolisms were significantly altered after pioglitazone administration. Further analysis of quantification of metabolites from purine metabolism, revealed that the xanthine/hypoxanthine and uric acid/xanthine ratios were significantly decreased at post-dose. Pioglitazone-dependent endogenous metabolites and metabolic ratio indicated the potential effect of pioglitazone on the activation of PPAR and fatty acid synthesis. Additional studies involving patients are required to validate these findings.PMID:38771175 | DOI:10.1111/cts.13834

Appl Environ Microbiol. 2024 May 21:e0060024. doi: 10.1128/aem.00600-24. Online ahead of print.ABSTRACTPolycyclic tetramate macrolactams (PTMs) are bioactive natural products commonly associated with certain actinobacterial and proteobacterial lineages. These molecules have been the subject of numerous structure-activity investigations since the 1970s. New members continue to be pursued in wild and engineered bacterial strains, and advances in PTM biosynthesis suggest their outwardly simplistic biosynthetic gene clusters (BGCs) belie unexpected product complexity. To address the origins of this complexity and understand its influence on PTM discovery, we engaged in a combination of bioinformatics to systematically classify PTM BGCs and PTM-targeted metabolomics to compare the products of select BGC types. By comparing groups of producers and BGC mutants, we exposed knowledge gaps that complicate bioinformatics-driven product predictions. In sum, we provide new insights into the evolution of PTM BGCs while systematically accounting for the PTMs discovered thus far. The combined computational and metabologenomic findings presented here should prove useful for guiding future discovery.IMPORTANCEPolycyclic tetramate macrolactam (PTM) pathways are frequently found within the genomes of biotechnologically important bacteria, including Streptomyces and Lysobacter spp. Their molecular products are typically bioactive, having substantial agricultural and therapeutic interest. Leveraging bacterial genomics for the discovery of new related molecules is thus desirable, but drawing accurate structural predictions from bioinformatics alone remains challenging. This difficulty stems from a combination of previously underappreciated biosynthetic complexity and remaining knowledge gaps, compounded by a stream of yet-uncharacterized PTM biosynthetic loci gleaned from recently sequenced bacterial genomes. We engaged in the following study to create a useful framework for cataloging historic PTM clusters, identifying new cluster variations, and tracing evolutionary paths for these molecules. Our data suggest new PTM chemistry remains discoverable in nature. However, our metabolomic and mutational analyses emphasize the practical limitations of genomics-based discovery by exposing hidden complexity.PMID:38771054 | DOI:10.1128/aem.00600-24

J Sci Food Agric. 2024 May 21. doi: 10.1002/jsfa.13607. Online ahead of print.ABSTRACTBACKGROUND: Mycotoxin surveys play an essential role in our food safety system. The obtained occurrence data form the basis for the assessment of the exposure of humans and animals to these toxic fungal secondary metabolites. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has become the gold standard for mycotoxin determination because it enables selective and sensitive multi-toxin analysis. Simultaneous determination of several hundreds of secondary fungal metabolites is feasible using this technique. In this study, we combined a targeted dilute-and-shoot LC-MS/MS-based multi-analyte approach with multivariate statistics for the analysis of Austrian wheat from two different years and different geographical origins.RESULTS: We quantified 47 secondary fungal metabolites, including regulated emerging and masked mycotoxins. The resulting multi-mycotoxin occurrence data were further analyzed using both multivariate and univariate statistics. Principal component analysis (PCA) and analysis of variance (ANOVA) simultaneous component analysis (ASCA) were employed to identify regional and yearly trends within the dataset and to quantify the variance in metabolite occurrence attributed to the different effects. In addition, secondary fungal metabolites significantly impacted by these factors were selected via ANOVA. Of the 47 secondary metabolites identified, 39 were affected by the year, region or a combined effect. Moreover, our findings show that 43 of the secondary fungal metabolites were significantly influenced by the weather conditions.CONCLUSION: The results presented in this study underline the added value of combining targeted LC-MS/MS with multivariate statistics for monitoring a broad spectrum of secondary fungal metabolites in food crops. Through multivariate statistics, trends associated with the year or region can be readily studied. The approach presented could pave the way for a better understanding of the impact of climate change on plant pathogenic fungi and its implications for food safety. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.PMID:38770945 | DOI:10.1002/jsfa.13607

J Cell Physiol. 2024 May 21. doi: 10.1002/jcp.31293. Online ahead of print.ABSTRACTThe sorting and assembly machinery (SAM) Complex is responsible for assembling β-barrel proteins in the mitochondrial membrane. Comprising three subunits, Sam35, Sam37, and Sam50, the SAM complex connects the inner and outer mitochondrial membranes by interacting with the mitochondrial contact site and cristae organizing system complex. Sam50, in particular, stabilizes the mitochondrial intermembrane space bridging (MIB) complex, which is crucial for protein transport, respiratory chain complex assembly, and regulation of cristae integrity. While the role of Sam50 in mitochondrial structure and metabolism in skeletal muscle remains unclear, this study aims to investigate its impact. Serial block-face-scanning electron microscopy and computer-assisted 3D renderings were employed to compare mitochondrial structure and networking in Sam50-deficient myotubes from mice and humans with wild-type (WT) myotubes. Furthermore, autophagosome 3D structure was assessed in human myotubes. Mitochondrial metabolic phenotypes were assessed using Gas Chromatography-Mass Spectrometry-based metabolomics to explore differential changes in WT and Sam50-deficient myotubes. The results revealed increased mitochondrial fragmentation and autophagosome formation in Sam50-deficient myotubes compared to controls. Metabolomic analysis indicated elevated metabolism of propanoate and several amino acids, including ß-Alanine, phenylalanine, and tyrosine, along with increased amino acid and fatty acid metabolism in Sam50-deficient myotubes. Furthermore, impairment of oxidative capacity was observed upon Sam50 ablation in both murine and human myotubes, as measured with the XF24 Seahorse Analyzer. Collectively, these findings support the critical role of Sam50 in establishing and maintaining mitochondrial integrity, cristae structure, and mitochondrial metabolism. By elucidating the impact of Sam50-deficiency, this study enhances our understanding of mitochondrial function in skeletal muscle.PMID:38770789 | DOI:10.1002/jcp.31293

Brief Bioinform. 2024 Mar 27;25(3):bbae240. doi: 10.1093/bib/bbae240.ABSTRACTPolygenetic Risk Scores are used to evaluate an individual's vulnerability to developing specific diseases or conditions based on their genetic composition, by taking into account numerous genetic variations. This article provides an overview of the concept of Polygenic Risk Scores (PRS). We elucidate the historical advancements of PRS, their advantages and shortcomings in comparison with other predictive methods, and discuss their conceptual limitations in light of the complexity of biological systems. Furthermore, we provide a survey of published tools for computing PRS and associated resources. The various tools and software packages are categorized based on their technical utility for users or prospective developers. Understanding the array of available tools and their limitations is crucial for accurately assessing and predicting disease risks, facilitating early interventions, and guiding personalized healthcare decisions. Additionally, we also identify potential new avenues for future bioinformatic analyzes and advancements related to PRS.PMID:38770718 | DOI:10.1093/bib/bbae240

Adv Neurotoxicol. 2024;11:105-132. doi: 10.1016/bs.ant.2024.02.001. Epub 2024 Feb 15.ABSTRACTParkinson's Disease (PD) is a progressive neurodegenerative disease characterized by loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Iron (Fe)-dependent programmed cell death known as ferroptosis, plays a crucial role in the etiology and progression of PD. Since SNpc is particularly vulnerable to Fe toxicity, a central role for ferroptosis in the etiology and progression of PD is envisioned. Ferroptosis, characterized by reactive oxygen species (ROS)-dependent accumulation of lipid peroxides, is tightly regulated by a variety of intracellular metabolic processes. Moreover, the recently characterized bi-directional interactions between ferroptosis and the gut microbiota, not only provides another window into the mechanistic underpinnings of PD but could also suggest novel interventions in this devastating disease. Here, following a brief discussion of PD, we focus on how our expanding knowledge of Fe-induced ferroptosis and its interaction with the gut microbiota may contribute to the pathophysiology of PD and how this knowledge may be exploited to provide novel interventions in PD.PMID:38770370 | PMC:PMC11105119 | DOI:10.1016/bs.ant.2024.02.001

Heliyon. 2024 May 9;10(10):e30828. doi: 10.1016/j.heliyon.2024.e30828. eCollection 2024 May 30.ABSTRACTModified Jiawei Juanbi decoction (MJD) is used for the treatment of early-stage knee osteoarthritis (KOA). Here, modified Jiawei Juanbi decoction (MJD) was employed for the treatment of early-stage knee osteoarthritis (KOA) and its mechanisms were assessed via metabonomics and network pharmacology. A total of 24 male Sprague-Dawley rats were randomly allocated into a normal control group, a model group, and an MJD group (n = 8 rats per group). Each rat group was further equally divided into two subgroups for investigation for either 14 or 28 days. A rat model of early-stage KOA was constructed and rats were treated with MJD. Effects were evaluated based on changes in knee circumference, mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). We also analyzed histopathological changes in articular cartilage. High-resolution mass spectrometry was used to analyze the chemical profile of MJD, identifying 228 components. Using an LC-Q-TOF-MS metabonomics approach, 33 differential metabolites were identified. The relevant pathways significantly associated with MJD include arginine and proline metabolism, vitamin B6 metabolism, as well as the biosynthesis of phenylalanine, tyrosine and tryptophan. The system pharmacology paradigm revealed that MJD contains 1027 components and associates with 1637 genes, of which 862 disease genes are related to osteoarthritis. The construction of the MJD composition-target-KOA network revealed a total of 140 intersection genes. A total of 39 hub genes were identified via integration of betweenness centrality values greater than 100 using CytoHubba. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed several significantly affected signaling pathways including the HIF-1, AGE-RAGE (in diabetic complications), IL-17, rheumatoid arthritis and TNF pathways. Integrated-omics and network pharmacology approaches revealed a necessity for further detailed investigation focusing on two major targets, namely NOS2 and NOS3, along with their essential metabolite (arginine) and associated pathways (HIF-1 signaling and arginine and proline metabolism). Real-time PCR validated significantly greater downregulation of NOS2 and HIF-1ɑ in the MJD as compared to the model group. Molecular docking analysis further confirmed the binding of active MJD with key active components. Our findings elucidate the impact of MJD on relevant pathophysiological and metabolic networks relevant to KOA and assess the drug efficacy of MJD and its underlying mechanisms of action.PMID:38770333 | PMC:PMC11103480 | DOI:10.1016/j.heliyon.2024.e30828

iScience. 2024 Apr 26;27(6):109830. doi: 10.1016/j.isci.2024.109830. eCollection 2024 Jun 21.ABSTRACTThe liver X receptor (LXR) is considered a therapeutic target for atherosclerosis treatment, but synthetic LXR agonists generally also cause hepatic steatosis and hypertriglyceridemia. Desmosterol, a final intermediate in cholesterol biosynthesis, has been identified as a selective LXR ligand that suppresses inflammation without inducing lipogenesis. Δ24-Dehydrocholesterol reductase (DHCR24) converts desmosterol into cholesterol, and we previously showed that the DHCR24 inhibitor SH42 increases desmosterol to activate LXR and attenuate experimental peritonitis and metabolic dysfunction-associated steatotic liver disease. Here, we aimed to evaluate the effect of SH42 on atherosclerosis development in APOE∗3-Leiden.CETP mice and low-density lipoproteins (LDL) receptor knockout mice, models for lipid- and inflammation-driven atherosclerosis, respectively. In both models, SH42 increased desmosterol without affecting plasma lipids. While reducing liver lipids in APOE∗3-Leiden.CETP mice, and regulating populations of circulating monocytes in LDL receptor knockout mice, SH42 did not attenuate atherosclerosis in either model.PMID:38770137 | PMC:PMC11103367 | DOI:10.1016/j.isci.2024.109830

Phytochem Anal. 2024 May 20. doi: 10.1002/pca.3385. Online ahead of print.ABSTRACTINTRODUCTION: The Olive (Olea europaea L.) is one of the most popular edible oil-producing fruits, consumed worldwide for its myriad nutritional and health benefits. Olive oil production generates huge quantities of by-products from the fruit, which are considered environmental hazards. Recently, more and more efforts have been made to valorize olive by-products as a source of low-cost, value-added food applications.OBJECTIVE: The main objective of this study was to globally assess the metabolome of olive fruit by-products, including olive mill wastewater, olive pomace, and olive seeds from fruits from two areas, Siwa and Anshas, Egypt.METHODS: Gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography with mass spectrometry (UPLC-MS) were used for profiling primary and secondary metabolites in olive by-products. Also, multivariate data analyses were used to assess variations between olive by-product samples.RESULTS: A total of 103 primary metabolites and 105 secondary metabolites were identified by GC-MS and UPLC-MS, respectively. Fatty acids amounted to a major class in the olive by-products at 53-91%, with oleic acid dominating, especially in the pomace of Siwa. Mill wastewater was discriminated from other by-products by the presence of phenolics mainly tyrosol, hydroxyl tyrosol, and α-tocopherol as analyzed by UPLC-MS indicating their potential antioxidant activity. Pomace and seeds were rich in fatty acids/esters and hydroxy fatty acids and not readily distinguishable from each other.CONCLUSION: The current work discusses the metabolome profile of olive waste products for valorization purposes. Pomace and seeds were enriched in fatty acids/esters, though not readily distinguishable from each other.PMID:38768954 | DOI:10.1002/pca.3385

J Ethnopharmacol. 2024 May 18:118362. doi: 10.1016/j.jep.2024.118362. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: In ancient times, ginseng was used for hyperuricemia treatment as described in the classic traditional Chinese medical text Shang Han Lun. Recent studies have shown that common ginsenosides and rare ginsenosides (RGS) are the main active compounds in ginseng. RGS have higher activity and are less studied in the treatment of hyperuricemia.AIM OF THE STUDY: To determine whether RGS prevents and ameliorates potassium oxonate(PO)-induced hyperuricemia and concomitant spermatozoa damage in mice and the possible underlying mechanisms.MATERIALS AND METHODS: Potassium oxonate (PO, 300 mg/kg) induced hyperuricemia in mice via the oral administration of RGS (50, 100, or 200 mg/kg) or allopurinol (ALL, 5 mg/kg) for 35 days. Uric acid (UA) and xanthine oxidase (XO) levels were measured to assess the degree of histopathological damage in the liver, kidney, and testis, and renal creatinine (CRE), urea nitrogen (BUN), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and inflammatory factor (IL-1β) levels were measured to calculate the sperm density. Mechanisms were also explored based on blood and urine metabolomics and the gut microbiota.RESULTS: In this study, we demonstrated that RGS containing Rg3, Rk1, Rg6, and Rg5 could reduce serum UA levels, inhibit serum and hepatic XO activity, reduce renal CRE and BUN levels, further restore renal SOD and GSH activities, reduce the accumulation of MDA in the kidneys, and attenuate the production of renal IL-1β. RGS was able to restore sperm density. Metabolomic analysis revealed that RGS improved sphingolipid metabolism, pyrimidine metabolism, and other metabolic pathways. 16S rDNA sequencing revealed that RGS could increase gut microbial diversity, restore the Firmicutes/Bacteroidetes (F/B) ratio, and adjust the intestinal microbial balance. Spearman's correlation analysis revealed a correlation between differentially metabolites and the gut microbiota. Lactobacillus and Akkermansia are the core genera.CONCLUSION: RGS can be a candidate for the prevention and amelioration of hyperuricemia and concomitant sperm damage. Its mechanism of action is closely related to sphingolipid metabolism, pyrimidine metabolism, and the modulation of gut microbiota, such as Lactobacillus and Akkermansia.PMID:38768838 | DOI:10.1016/j.jep.2024.118362

J Affect Disord. 2024 May 18:S0165-0327(24)00817-6. doi: 10.1016/j.jad.2024.05.083. Online ahead of print.ABSTRACTBACKGROUND: Postpartum depression (PPD) is a serious psychiatric disorder that has significantly adverse impacts on maternal health. Metabolic abnormalities in the brain are associated with numerous neurological disorders, yet the specific metabolic signaling pathways and brain regions involved in PPD remain unelucidated.METHODS: We performed behavioral test in the virgin and postpartum mice. We used mass spectrometry imaging (MSI) and targeted metabolomics analyses to investigate the metabolic alternation in the brain of GABAAR Delta-subunit-deficient (Gabrd-/-) postpartum mice, a specific preclinical animal model of PPD. Next, we performed mechanistic studies including qPCR, Western blot, immunofluorescence staining, electron microscopy and primary astrocyte culture. In the specific knockdown and rescue experiments, we injected the adeno-associated virus into the central amygdala (CeA) of female mice.RESULTS: We identified that prostaglandin D2 (PGD2) downregulation in the CeA was the most outstanding alternation in PPD, and then validated that lipocalin-type prostaglandin D synthase (L-PGDS)/PGD2 downregulation plays a causal role in depressive behaviors derived from PPD in both wild-type and Gabrd-/- mice. Furthermore, we verified that L-PGDS/PGD2 signaling dysfunction-induced astrocytes atrophy is mediated by Src phosphorylation both in vitro and in vivo.LIMITATIONS: L-PGDS/PGD2 signaling dysfunction may be only responsible for the depressive behavior rather than maternal behaviors in the PPD, and it remains to be seen whether this mechanism is applicable to all depression types..CONCLUSION: Our study identified abnormalities in the L-PGDS/PGD2 signaling in the CeA, which inhibited Src phosphorylation and induced astrocyte atrophy, ultimately resulting in the development of PPD in mice.PMID:38768820 | DOI:10.1016/j.jad.2024.05.083

J Control Release. 2024 May 18:S0168-3659(24)00313-4. doi: 10.1016/j.jconrel.2024.05.029. Online ahead of print.ABSTRACTProstate cancer (PCa) is a global health concern, ranking as the most common cancer among men in Western countries. Traditional diagnostic methods are invasive with adverse effects on patients. Due to the heterogeneous nature of PCa and their multifocality, tissue biopsies often yield false-negative results. To address these challenges, researchers are exploring innovative approaches, particularly in the realms of proteomics and metabolomics, to identify more reliable biomarkers and improve PCa diagnosis. Liquid biopsy (LB) has emerged as a promising non-invasive strategy for PCa early detection, biopsy selection, active surveillance for low-risk cases, and post-treatment and progression monitoring. Extracellular vesicles (EVs) are lipid-bilayer nanovesicles released by all cell types and play an important role in intercellular communication. EVs have garnered attention as a valuable biomarker resource in LB for PCa-specific biomarkers, enhancing diagnosis, prognostication, and treatment guidance. Metabolomics provides insight into the body's metabolic response to both internal and external stimuli, offering quantitative measurements of biochemical alterations. It excels at detecting non-genetic influences, aiding in the discovery of more accurate cancer biomarkers for early detection and disease progression monitoring. This review delves into the potential of EVs as a resource for LB in PCa across various clinical applications. It also explores cancer-related metabolic biomarkers, both within and outside EVs in PCa, and summarises previous metabolomic findings in PCa diagnosis and risk assessment. Finally, the article addresses the challenges and future directions in the evolving field of EV-based metabolomic analysis, offering a comprehensive overview of its potential in advancing PCa management.PMID:38768661 | DOI:10.1016/j.jconrel.2024.05.029

Phytochem Anal. 2024 May 20. doi: 10.1002/pca.3367. Online ahead of print.ABSTRACTINTRODUCTION: Lipid molecules are present in tumours and play an important role in the anti-inflammatory response as well as in antiviral protection. Changes in the type and location of lipids in the intestine following exposure to environmental stressors play an important role in several disorders, including ulcerative colitis (UC), inflammatory bowel disease (IBD), and colorectal cancer.OBJECTIVES: The aim of this work is to provide a new theoretical basis for tumour initiation and development by accurately measuring the spatial distribution of lipids and metabolites in intestinal tissue. Spatial metabolomics allows the detection of samples with minimal sample volume by label-free imaging of complex samples in their original state. The distribution of lipid molecules in tumours has not been reported, although the distribution of lipid molecules in intestinal tissue has been reported in the literature.METHODS: The range of lipid profiles in colon cancer mouse tumour tissue was compiled using a spatial metabolomics: lipid extraction method. The changes in lipid distribution in two regions after oral administration of American Ginseng (Panax quinquefolius L.) vesicles were also compared. Tumour tissue samples were extracted with 80% methanol-20% formic acid in water.RESULTS: The resulting spatial metabolic profile allowed the identification of seven lipid classes in mouse tumours. The distribution of fibre tissue cells was 23.2% higher than tumour tissue cells, with the exception of the fatty acid (FA) species.PMID:38768606 | DOI:10.1002/pca.3367

BMC Biotechnol. 2024 May 20;24(1):33. doi: 10.1186/s12896-024-00860-7.NO ABSTRACTPMID:38769530 | DOI:10.1186/s12896-024-00860-7

Nat Commun. 2024 May 20;15(1):4292. doi: 10.1038/s41467-024-48427-6.ABSTRACTDeficiencies in the BRCA1 tumor suppressor gene are the main cause of hereditary breast and ovarian cancer. BRCA1 is involved in the Homologous Recombination DNA repair pathway and, together with BARD1, forms a heterodimer with ubiquitin E3 activity. The relevance of the BRCA1/BARD1 ubiquitin E3 activity for tumor suppression and DNA repair remains controversial. Here, we observe that the BRCA1/BARD1 ubiquitin E3 activity is not required for Homologous Recombination or resistance to Olaparib. Using TULIP2 methodology, which enables the direct identification of E3-specific ubiquitination substrates, we identify substrates for BRCA1/BARD1. We find that PCNA is ubiquitinated by BRCA1/BARD1 in unperturbed conditions independently of RAD18. PCNA ubiquitination by BRCA1/BARD1 avoids the formation of ssDNA gaps during DNA replication and promotes continuous DNA synthesis. These results provide additional insight about the importance of BRCA1/BARD1 E3 activity in Homologous Recombination.PMID:38769345 | DOI:10.1038/s41467-024-48427-6

Curr Microbiol. 2024 May 20;81(7):182. doi: 10.1007/s00284-024-03724-7.ABSTRACTFusarium proliferatum is the main pathogen that causes Panax notoginseng root rot. The shortcomings of strong volatility and poor water solubility of Illicium verum essential oil (EO) limit its utilization. In this study, we prepared traditional emulsion (BDT) and nanoemulsion (Bneo) of I. verum EO by ultrasonic method with Tween-80 and absolute ethanol as solvents. The chemical components of EO, BDT, and Bneo were identified by gas chromatography-mass spectrometry (GC-MS) and the antifungal activity and mechanism were compared. The results show that Bneo has good stability and its particle size is 34.86 nm. The contents of (-) -anethole and estragole in Bneo were significantly higher than those in BDT. The antifungal activity against F. proliferatum was 5.8-fold higher than BDT. In the presence of I. verum EO, the occurrence of P. notoginseng root rot was significantly reduced. By combining transcriptome and metabolomics analysis, I. verum EO was found to be involved in the mutual transformation of pentose and glucuronic acid, galactose metabolism, streptomycin biosynthesis, carbon metabolism, and other metabolic pathways of F. proliferatum, and it interfered with the normal growth of F. proliferatum to exert antifungal effects. This study provide a theoretical basis for expanding the practical application of Bneo.PMID:38769214 | DOI:10.1007/s00284-024-03724-7