PubMed

Plant Physiol Biochem. 2024 Aug 31;215:109081. doi: 10.1016/j.plaphy.2024.109081. Online ahead of print.ABSTRACTThe garden strawberry (Fragaria x ananassa Duch.) is cultivated and consumed worldwide because of the pleasant flavor and health-promoting phytochemicals of its false fruits. Monocrop cultivars produce fully ripe strawberries in about one month post-anthesis throughout the spring, while everbearing cultivars undergo additional strawberry production in autumn. In this work, we evaluated the impact of different season-dependent environmental conditions on the ripening program of an everbearing field-gown strawberry variety from autumn 2015 to spring 2016. We combined ad hoc sampling and environmental data collection with LC-MS-based untargeted metabolomics to dissect the effects of cumulative temperature and solar irradiation on fruit quality parameters and secondary metabolism during ripening. Different dynamics in specific sub-groups of metabolites were observed in strawberries experiencing distinct amounts of cumulative temperature and solar irradiation during spring and autumn. The integration of statistical analyses on collected data revealed that solar irradiation mainly affected fruit fresh weight and organic acid levels, whereas temperature had a more selective effect on the accumulation of specific flavonols, anthocyanins, and soluble sugar. These findings are of suitable interest to design further approaches for the study of the complex interactions among environmental conditions and ripening in strawberries grown in a real-world scenario.PMID:39222548 | DOI:10.1016/j.plaphy.2024.109081

ChemSusChem. 2024 Sep 2:e202401033. doi: 10.1002/cssc.202401033. Online ahead of print.ABSTRACTCathodic Electro Fermentation (CEF) is an innovative approach to manage the spectrum of products deriving from anaerobic fermentation. Herein, mixed microbial culture fermentation using a ternary mixture containing labelled 13C glucose and non-labelled acetate and ethanol was studied to identify the role of polarization on the metabolic pathways of glucose fermentation. CEF at an applied potential of -700 mV (vs. SHE, Standard Hydrogen Electrode) enhanced the production yield of acetate, propionate, and butyrate (0.90 ± 0.10, 0.22 ± 0.03, and 0.34 ± 0.05 mol/mol; respectively) compared to control tests performed at open circuit potential (OCP) (0.54 ± 0.09, 0.15 ± 0.04 and, 0.21 ± 0.001 mol/mol, respectively). Results indicate that CEF affected the 13C labelled fermented product levels and their fractional 13C enrichments, allowing to establish metabolic pathway models. This work demonstrates that, under cathodic polarization, the abundance of both fully 13C labelled propionate and butyrate isotopomers increased compared to control tests. The effect of CEF is mainly due to intermediates initially produced from the glucose metabolic transformation in the presence of non-labelled acetate and ethanol as external substrates. These findings represent a significant advancement in current knowledge of CEF, which offers a promising tool to control mixed cultures bioprocesses.PMID:39222403 | DOI:10.1002/cssc.202401033

Ann Surg Oncol. 2024 Sep 2. doi: 10.1245/s10434-024-16125-8. Online ahead of print.ABSTRACTBACKGROUND: Gastrectomy is one of the main treatment modalities for gastric cancer (GC) and induces pathophysiological changes that significantly affect patients' postoperative recovery. In this study, we investigated the relationships between altered insulin resistance (IR), inflammation, and gut microbiota associated with gastrectomy.PATIENTS AND METHODS: This study was a single-center prospective cohort investigation involving 60 patients with GC who underwent gastrectomy between May 2023 and April 2024. Monitoring encompassed IR, inflammation, and nutrition-related markers via blood assays, while gut microbiota analysis employed high-throughput sequencing, and short-chain fatty acids (SCFAs) were examined through targeted metabolomics. The study is registered under the number ChiCTR2300075653.RESULTS: The patients exhibited a significant increase in post-gastrectomy IR markers (P < 0.001), accompanied by elevated inflammation markers (P < 0.001), and also showed decreased nutrition-related indicators (P < 0.001). Notable alterations were observed in the gut microbiota, including reductions in Bifidobacterium and Faecalibacterium, an increase in Streptococcus, and a noteworthy decrease in fecal butyrate. Patients with postoperative IR exhibited poorer inflammation markers (P < 0.05), nutritional indicators (P < 0.05), and postoperative recovery parameters (P < 0.05). Furthermore, significant negative correlations were observed between IR and Bifidobacterium, Faecalibacterium, as well as butyrate.CONCLUSIONS: Patients with GC post-gastrectomy displayed heightened IR, exacerbated inflammation, and compromised nutritional status. Disturbed gut microbiota and reduced fecal butyrate were observed. Gut microbiota and metabolite butyrate production may be predictors of postoperative IR and short-term outcomes in patients with GC.PMID:39222298 | DOI:10.1245/s10434-024-16125-8

Environ Toxicol. 2024 Sep 2. doi: 10.1002/tox.24417. Online ahead of print.ABSTRACTChloroform is a prevalent toxic environmental pollutant in urban settings, posing risks to human health through exposure via various mediums such as air and tap water. The gut microbiota plays a pivotal role in maintaining host health. However, there is a paucity of research elucidating the impact of chloroform exposure on the gut microbiota. In this investigation, 18 SPF Kunming female mice were stratified into three groups (n = 6) and subjected to oral gavage with chloroform doses equivalent to 0, 50, and 150 mg/kg of body weight over 30 days. Our findings demonstrate that subchronic chloroform exposure significantly perturbs hematological parameters in mice and induces histopathological alterations in cecal tissues, consequently engendering marked disparities in the functional composition of cecal microbiota and metabolic equilibrium of cecal contents. Ultimately, our investigation revealed a statistically robust correlation, exhibiting a high degree of significance, between the intestinal microbiome composition and the metabolites that were differentially expressed consequent to chloroform exposure.PMID:39221872 | DOI:10.1002/tox.24417

Anal Chem. 2024 Sep 2. doi: 10.1021/acs.analchem.4c02989. Online ahead of print.ABSTRACTMacrophages consist of a heterogeneous population of functionally distinct cells that participate in many physiological and pathological processes. They exhibit prominent plasticity by changing their different functional phenotypes represented by proinflammatory (M1) and anti-inflammatory (M2) in response to different environmental stimuli. Emerging evidence illustrates the importance of intracellular metabolic pathways in macrophage polarizations and functions. In the tumor microenvironment (TME), macrophages tend to M2 polarization, which promotes tumor growth and leads to adverse physiological effects. Due to the lack of highly specific antigens in M1 and M2 macrophages, significant challenges present in isolating these subtypes from clinical samples or in vitro coculture models of tumor-immune cells. In reverse, the single-cell technique provides the possibility to investigate the factors influencing macrophage polarization in the TME. In this research, we employed inertial microfluidic chip-mass spectrometry (IMC-MS) to conduct single-cell metabolomics analysis of macrophages polarized into the two major phenotypes, respectively, and 213 metabolites were identified in total. Subsequently, differential metabolites between macrophage phenotypes were analyzed using volcano plots and binary logistic regression models. Glutamine was pinpointed as a key metabolite for the M1 and M2 phenotypes. Experimental results from both monoculture and coculture cell models demonstrated that M1 polarization is more reliant on the presence of glutamine in the culture environment than M2 polarization. Glutamine deficiency resulted in failed M1 polarization, while its absence had a less pronounced effect on M2 polarization. Replenishing an appropriate amount of glutamine during the intermediate stages of coculture models significantly enhanced the proportion of M1 polarization and suppressed the growth of tumor cells. This research elucidated glutamine as a key factor influencing macrophage polarization in the TME via single-cell metabolomics based on IMC-MS, offering promising insights and targets for tumor therapies.PMID:39221578 | DOI:10.1021/acs.analchem.4c02989

Gut Microbes Rep. 2024;1(1):1-23. doi: 10.1080/29933935.2024.2387936. Epub 2024 Aug 19.ABSTRACTThe human gut microbiome (GM) undergoes dynamic changes throughout life, transitioning from infancy to adulthood. Despite improved understanding over the past years about how genetics, lifestyle, and the external environment impact the GM, limited research has explored the GM's evolution during late-stage adolescence, especially among college students. This study addresses this gap by investigating the longitudinal dynamics of fecal microbial, functional, and metabolomic signatures in a diverse group of first-year, dormitory-housed college students. A total of 485 stool samples from 246 participants were analyzed, identifying four primary GM community types, predominantly led by Bacteroides (66.8% of samples), as well as Blautia and Prevotella. The Prevotella/Bacteroides (P/B) ratio emerged as a robust GM composition indicator, predictively associated with 15 metabolites. Notably, higher P/B ratios correlated negatively with p-cresol sulfate and cholesterol sulfate, implying potential health implications, while positively correlating with kynurenic acid. Distinct GM transition and stability patterns were found from a detailed longitudinal subset of 93 participants over an academic year. Parasutterella and the Ruminococcus gnavus group exhibited positive associations with compositional variability, whereas Faecalibacterium and Eubacterium ventriosum group displayed negative associations, the latter suggesting stabilizing roles in the GM. Most notably, nearly half of the longitudinal cohort experienced GM community shifts, emphasizing long-term GM adaptability. Comparing individuals with stable community types to those undergoing transitions, we observed significant differences in microbial composition and diversity, signifying substantial shifts in the microbiota during transitions. Although diet-related variables contributed to some observed variance, diet did not independently predict the probability of switching between community types within the study's timeframe via multi-state Markov modeling. Furthermore, exploration of stability within dynamic microbiomes among the longitudinal cohort experiencing shifts in community types revealed that microbiome taxa at the genus level exhibited significantly higher total variance than estimated functional and fecal metabolomic features. This suggests tight control of function and metabolism, despite community shifting. Overall, this study highlights the dynamic nature of the late-stage adolescent GM, the role of core taxa, metabolic pathways, the fecal metabolome, and lifestyle and dietary factors, contributing to our understanding of GM assembly and potential health implications during this life phase.PMID:39221110 | PMC:PMC11361303 | DOI:10.1080/29933935.2024.2387936

F1000Res. 2024 Apr 8;11:1191. doi: 10.12688/f1000research.124194.2. eCollection 2022.ABSTRACTBACKGROUND: Metabolomics is the simultaneous determination of all metabolites in a system. Despite significant advances in the field, compound identification remains a challenge. Prior knowledge of the compound classes of interest can improve metabolite identification. Hormones are a small signaling molecules, which function in coordination to direct all aspects of development, function and reproduction in living systems and which also pose challenges as environmental contaminants. Hormones are inherently present at low levels in tissues, stored in many forms and mobilized rapidly in response to a stimulus making them difficult to measure, identify and quantify.METHODS: An in-depth literature review was performed for known hormones, their precursors, metabolites and conjugates in plants to generate the database and an RShiny App developed to enable web-based searches against the database. An accompanying liquid chromatography - mass spectrometry (LC-MS) protocol was developed with retention time prediction in Retip. A meta-analysis of 14 plant metabolomics studies was used for validation.RESULTS: We developed HormonomicsDB, a tool which can be used to query an untargeted mass spectrometry (MS) dataset against a database of more than 200 known hormones, their precursors and metabolites. The protocol encompasses sample preparation, analysis, data processing and hormone annotation and is designed to minimize degradation of labile hormones. The plant system is used a model to illustrate the workflow and data acquisition and interpretation. Analytical conditions were standardized to a 30 min analysis time using a common solvent system to allow for easy transfer by a researcher with basic knowledge of MS. Incorporation of synthetic biotransformations enables prediction of novel metabolites.CONCLUSIONS: HormonomicsDB is suitable for use on any LC-MS based system with compatible column and buffer system, enables the characterization of the known hormonome across a diversity of samples, and hypothesis generation to reveal knew insights into hormone signaling networks.PMID:39221023 | PMC:PMC11364965 | DOI:10.12688/f1000research.124194.2

Heliyon. 2024 Aug 8;10(16):e35974. doi: 10.1016/j.heliyon.2024.e35974. eCollection 2024 Aug 30.ABSTRACTMentha spicata is a popular herb used in foods, cosmetics, and medicines. In the present study, liquid chromatography-mass spectrometry-based metabolomics analysis and the zebrafish model were used to investigate the potential biomarkers of M. spicata growing in Shanghe County (Shandong Province, China) and their anti-inflammatory properties. Network pharmacology and molecular docking were performed to screen the main targets of the characteristic compounds to understand their mechanisms of action. Nine potential markers including sugars (1,2), polyphenolic acids (3-5), and flavonoids (6-9) were identified from the species. The inhibitory effects on leukocyte migration confirmed that compounds 1 and 3-9 played a positive role in the protective effect of Shanghe M. spicata (SM) extract against inflammation. Akt (protein kinase B), EGFR (epidermal growth factor receptor), and MMP9 (matrix metalloproteinase 9) were the core target proteins of the identified compounds in the anti-inflammatory process. The most significant Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment terms were response to abiotic stimulus (Biological Process), carbohydrate derivative binding (Molecular Function), and pathways in cancer. In docking simulations, 3-p-coumaroylquinic acid (3-PC, 4) and cirsimaritin (CN, 7) exhibited the highest potential affinity to the active sites of Akt and EGFR proteins, respectively; additionally, 5-demethylsinensetin (5-DS, 9) and luteolin (LN, 6) were considered the most suitable ligands for the MMP9 protein. The present study highlighted the use of SM resources as functional products with health benefits.PMID:39220934 | PMC:PMC11365440 | DOI:10.1016/j.heliyon.2024.e35974

Heliyon. 2024 Aug 5;10(16):e35801. doi: 10.1016/j.heliyon.2024.e35801. eCollection 2024 Aug 30.ABSTRACTCamel milk is a nutrient-rich diet and fermentation affects its nutritional value and probiotic function. In this study, sour camel milk and oat jujube sour camel milk were prepared using fermentation bacteria agent TR1, and the metabolites of camel milk, sour camel milk and oat jujube sour camel milk were detected using a non-targeted metabolomics approach using liquid chromatography-mass spectrometry (LC-MS).The results showed that the partial least squares discriminant analysis (PLS-DA) with 100 % accuracy and good predictive power detected 343 components in positive ion mode and 220 components in negative ion mode. The differential metabolites were mainly organic acids, amino acids, esters, vitamins and other substances contained in camel milk.It showed that there were significant differences in the metabolites of camel milk, sour camel milk and oat jujube sour camel milk. Based on the pathway enrichment analysis of the three dairy products in the KEGG database, 12 metabolic pathways mainly involved in the positive ion mode and 20 metabolic pathways mainly involved in the negative ion mode were identified. The main biochemical metabolic pathways and signal transduction pathways of the differential metabolites of the three dairy products were obtained. This study provides theoretical support for improving the nutritional quality and probiotic function of camel milk and fermented camel milk products and provides a basis for the development of relevant processing technologies and products for camel milk and fermented camel milk.PMID:39220917 | PMC:PMC11365327 | DOI:10.1016/j.heliyon.2024.e35801

Acta Pharm Sin B. 2024 Aug;14(8):3385-3415. doi: 10.1016/j.apsb.2024.04.027. Epub 2024 May 3.ABSTRACTBile acids (BAs) are synthesized by the host liver from cholesterol and are delivered to the intestine, where they undergo further metabolism by gut microbes and circulate between the liver and intestines through various transporters. They serve to emulsify dietary lipids and act as signaling molecules, regulating the host's metabolism and immune homeostasis through specific receptors. Therefore, disruptions in BA metabolism, transport, and signaling are closely associated with cholestasis, metabolic disorders, autoimmune diseases, and others. Botanical triterpenoids and steroids share structural similarities with BAs, and they have been found to modulate BA metabolism, transport, and signaling, potentially exerting pharmacological or toxicological effects. Here, we have updated the research progress on BA, with a particular emphasis on new-found microbial BAs. Additionally, the latest advancements in targeting BA metabolism and signaling for disease treatment are highlighted. Subsequently, the roles of botanical triterpenoids in BA metabolism, transport, and signaling are examined, analyzing their potential pharmacological, toxicological, or drug interaction effects through these mechanisms. Finally, a research paradigm is proposed that utilizes the gut microbiota as a link to interpret the role of these important natural products in BA signaling.PMID:39220868 | PMC:PMC11365449 | DOI:10.1016/j.apsb.2024.04.027

Acta Pharm Sin B. 2024 Aug;14(8):3591-3604. doi: 10.1016/j.apsb.2024.04.019. Epub 2024 Apr 24.ABSTRACTAcute pancreatitis (AP) is a potentially fatal condition with no targeted treatment options. Although inhibiting xanthine oxidase (XO) in the treatment of AP has been studied in several experimental models and clinical trials, whether XO is a target of AP and what its the main mechanism of action is remains unclear. Here, we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP. We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models. We also found that allopurinol and febuxostat, as purine-like and non-purine XO inhibitors, respectively, exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points. Moreover, we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity. Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha (HIF-1α)-regulated lactate dehydrogenase A (LDHA) and NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathways and reduced the enrichment of 13C6-glucose to 13C3-lactate. Lastly, we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels, while pancreatic XO and urate were also increased in severe AP patients. These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.PMID:39220867 | PMC:PMC11365396 | DOI:10.1016/j.apsb.2024.04.019

Neuropsychiatr Dis Treat. 2024 Aug 27;20:1629-1639. doi: 10.2147/NDT.S471744. eCollection 2024.ABSTRACTPURPOSE: Parkinson's disease (PD) is a common neurodegenerative disease that severely affects patients' daily lives and places a significant burden on the global economy. There are currently no specific biomarkers for distinguishing between the different stages of PD.METHODS: We divided 78 mice into six equal groups, including five model PD groups (W1-W5; based on the PD stage induced by length of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/propofol induction time) and a control group. Then, we used metabolomics technology to detect the serum small-molecule metabolites present in each group. Ultimately, we screened for potential biomarkers using the variable importance in the projection of the orthogonal partial least squares discriminant analysis and the coefficient value of LASSO ordinal logistic regression.RESULTS: We identified 12 potential biomarkers, including dehydroepiandrosterone sulfate, pipecolic acid, N-acetylleucine, 2-aminoadipic acid, L-tyrosine, uric acid, and 5-hydroxyindoleacetaldehyde. Pathway analysis revealed their involvement in amino acid metabolism, caffeine metabolism, steroid hormone biosynthesis, and purine metabolism. Additionally, the receiver operating characteristic curve indicated that a biomarker panel comprising the 12 biomarkers could differentiate between the different PD stages.CONCLUSION: Different PD stages are characterized by different metabolites. The biomarkers identified in this study are helpful to understand the PD process.PMID:39220601 | PMC:PMC11365497 | DOI:10.2147/NDT.S471744

Front Cell Infect Microbiol. 2024 Aug 16;14:1381209. doi: 10.3389/fcimb.2024.1381209. eCollection 2024.ABSTRACTBACKGROUND: Hepatic encephalopathy (HE) is a neurological disorder resulting from advanced liver injury. HE has a high mortality rate and poor prognosis. The pathogenesis of HE is still unclear, which has led to the lack of a satisfactory specific treatment method. There is increasing evidence that the intestinal flora affects the communication between the gut and the brain in the pathogenesis of HE. Adjusting the intestinal flora has had a beneficial effect on HE in recent studies, and the Qingchang Ligan formula (QCLG) has been shown in previous studies to regulate intestinal flora and metabolites. In this study, we established a thioacetamide-induced HE mouse model to evaluate the protective effect of QCLG on HE and explore its potential mechanism, which also demonstrated that intestinal flora dysbiosis is involved in the pathogenesis of HE.METHODS: Mice were intraperitoneally injected with thioacetamide (TAA, 150 mg/kg) to induce HE. Additionally, they were orally administered Qingchang Ligan Formula (QCLG) at a dose of 6.725 g/kg·d for seven days, while control mice received an equal volume of saline via gavage. Subsequently, samples were subjected to 16S ribosomal ribonucleic acid (rRNA) gene sequencing, high-performance liquid chromatography-mass spectrometry (LC-MS), and RNA-sequencing (RNA-seq) analysis.RESULT: QCLG improved weight loss, cognitive impairment, neurological function scores, blood ammonia, and brain gene expression of interleukin-6 (TNF-α), Interleukin-1β (IL-1β), and interleukin-6 (IL-6) induced by HE. Moreover, QCLG increased the levels of liver function indicators, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum TNF-α, IL-1β, and IL-6. 16S RNA sequencing revealed increased Oscillibacter, Colidextribacter, and Helicobacter in TAA-induced mouse fecal samples. Also, the abundance of Bifidobacterium decreases TAA-induced mouse fecal samples. In contrast, QCLG treatment significantly restored the gut microbial community. Metabolomics indicated significant differences in some metabolites among the normal control, treatment, and model groups, including 5-methoxytryptophan, Daidzein, Stercobilin, and Plumieride (PLU).CONCLUSION: QCLG can alleviate neuroinflammation and prevent HE caused by liver injury by regulating intestinal flora in mouse models.PMID:39220284 | PMC:PMC11362135 | DOI:10.3389/fcimb.2024.1381209

iScience. 2024 Jul 27;27(9):110597. doi: 10.1016/j.isci.2024.110597. eCollection 2024 Sep 20.ABSTRACTArticular cartilage degeneration may lead to osteoarthritis (OA) during the aging process, but its underlying mechanism remains unknown. Here, we found that chondrocytes exhibited an energy metabolism shift from glycolysis to oxidative phosphorylation (OXPHOS) during aging. Parkin regulates various cellular metabolic processes. Reprogrammed cartilage metabolism by Parkin ablation decreased OXPHOS and increased glycolysis, with ameliorated aging-related OA. Metabolomics analysis indicated that lauroyl-L-carnitine (LLC) was decreased in aged cartilage, but increased in Parkin-deficient cartilage. In vitro, LLC improved the cartilage matrix synthesis of aged chondrocytes. In vivo, intra-articular injection of LLC in mice with anterior cruciate ligament transaction (ACLT) ameliorated OA progression. These results suggest that metabolic changes are regulated by Parkin-impaired cartilage during aging, and targeting this metabolomic changes by supplementation with LLC is a promising treatment strategy for ameliorating OA.PMID:39220257 | PMC:PMC11363567 | DOI:10.1016/j.isci.2024.110597

Front Microbiol. 2024 Aug 16;15:1453436. doi: 10.3389/fmicb.2024.1453436. eCollection 2024.ABSTRACTBACKGROUND: Diabetic retinopathy (DR) is one of the common chronic complications of diabetes mellitus, which has developed into the leading cause of irreversible visual impairment in adults worldwide. Compound Qilian tablets (CQLT) is a traditional Chinese medicine (TCM) developed for treating DR, but its mechanism is still unclear. This study explored the mechanism of action of CQLT in treating DR through metabolomics and intestinal microbiota.METHODS: Histopathologic examination of the pancreas and retina of Zucker diabetic fatty (ZDF) rats and immunohistochemistry were used to determine the expression levels of retinal nerve damage indicators ionized calcium binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). Rat fecal samples were tested by LC-MS metabolomics to search for potential biomarkers and metabolic pathways for CQLT treatment of DR. Characteristic nucleic acid sequences of rat intestinal microbiota from each group were revealed using 16S rDNA technology to explore key microbes and related pathways for CQLT treatment of DR. At the same time, we investigated the effect of CQLT on the gluconeogenic pathway.RESULTS: After CQLT intervention, islet cell status was improved, Iba-1 and GFAP expression were significantly decreased, and abnormal retinal microvascular proliferation and exudation were ameliorated. Metabolomics results showed that CQLT reversed 20 differential metabolites that were abnormally altered in DR rats. Intestinal microbiota analysis showed that treatment with CQLT improved the abundance and diversity of intestinal flora. Functional annotation of metabolites and intestinal flora revealed that glycolysis/gluconeogenesis, alanine, aspartate and glutamate metabolism, starch and sucrose metabolism were the main pathways for CQLT in treating DR. According to the results of correlation analysis, there were significant correlations between Iba-1, GFAP, and intestinal microbiota and metabolites affected by CQLT. In addition, we found that CQLT effectively inhibited the gluconeogenesis process in diabetic mice.CONCLUSION: In conclusion, CQLT could potentially reshape intestinal microbiota composition and regulate metabolite profiles to protect retinal morphology and function, thereby ameliorating the progression of DR.PMID:39220039 | PMC:PMC11362098 | DOI:10.3389/fmicb.2024.1453436

Front Plant Sci. 2024 Aug 16;15:1428272. doi: 10.3389/fpls.2024.1428272. eCollection 2024.ABSTRACTINTRODUCTION: Salicylic acid (SA) is a phenolic compound widely found in plants. It plays a key role in exerting plant disease resistance. Panax vietnamensis Ha & Grushv., a valuable medicinal plant, contains high levels of phenolic compounds, which contribute significantly to the resilience of the plant against stress. However, the precise role of SA in regulating the synthesis of secondary metabolites in P.vietnamensis remains elusive.METHODS: Two-year-old P. vietnamensis seedlings were treated with exogenous SA. We systematically assessed the changes in the physiological parameters of SA-treated P. vietnamensis leaves, employing transcriptome and metabolome analyses to elucidate the underlying mechanisms.RESULTS: Our results revealed a significant improvement of the plant's antioxidant capacity at 6 h post-treatment. Furthermore, exogenous SA treatment promoted the biosynthesis of lignin and flavonoids such as rutin, coumarin, and cyanidin. In addition, it increased the levels of endogenous SA and jasmonic acid (JA), promoting the disease resistance of the plants. Thus, SA pretreatment enhanced the defense of P. vietnamensis against pathogens.CONCLUSIONS: Our study provided novel insights into the potential molecular mechanisms underlying SA-mediated biosynthesis of secondary metabolites. Furthermore, our results provided a theoretical foundation for optimizing the cultivation practices of P.vietnamensis and the application of SA as a plant immunomodulator.PMID:39220009 | PMC:PMC11362055 | DOI:10.3389/fpls.2024.1428272

Front Plant Sci. 2024 Aug 16;15:1418585. doi: 10.3389/fpls.2024.1418585. eCollection 2024.ABSTRACTINTRODUCTION: Dandelion is widely used in clinical practice due to its beneficial effects. Polyphenolic compounds are considered the main anti-inflammatory active ingredient of dandelion, but the gene expression patterns of polyphenolic compounds in different dandelion tissues are still unclear.METHODS: In this study, we combined a nontargeted metabolome, PacBio Iso-seq transcriptome, and Illumina RNA-seq transcriptome to investigate the relationship between polyphenols and gene expression in roots, flowers, and leaves of flowering dandelion plants.RESULTS: Eighty-eight flavonoids and twenty-five phenolic acids were identified, and 64 candidate genes involved in flavonoid biosynthesis and 63 candidate genes involved in chicoric acid biosynthesis were identified. Most flavonoid and chicoric acid-related genes demonstrated the highest content in flowers. RNA-seq analysis revealed that genes involved in polyphenol biosynthesis pathways, such as CHS, CHI, F3H, F3'H, FLS, HQT, and CAS, which are crucial for the accumulation of flavonoids and chicoric acid, were upregulated in flowers.DISCUSSION: The combination of transcriptomic and metabolomic data can help us better understand the biosynthetic pathways of polyphenols in dandelion. These results provide abundant genetic resources for further studying the regulatory mechanism of dandelion polyphenol biosynthesis.PMID:39220008 | PMC:PMC11361933 | DOI:10.3389/fpls.2024.1418585

JVS Vasc Sci. 2024 Jun 19;5:100208. doi: 10.1016/j.jvssci.2024.100208. eCollection 2024.ABSTRACTOBJECTIVE: We examined the associations between 25-hydroxy vitamin D (25(OH)D3) concentration and the diagnosis and growth of abdominal aortic aneurysm (AAA).METHODS: AAA cases and healthy controls were recruited from vascular centers or the community. A subset of participants with AAA were monitored by repeat ultrasound examination to assess AAA growth. Serum 25(OH)D3 concentration was measured using a validated mass spectrometry method and categorized into guideline-recommended cut-points after deseasonalization. The associations between deseasonalized 25(OH)D3 concentration and AAA diagnosis and growth were examined using logistic regression and linear mixed effects modeling.RESULTS: A total of 4673 participants consisting of 873 (455 controls and 418 cases) from Queensland and 3800 (3588 controls and 212 cases) from Western Australia were recruited. For every 1 standard deviation increase in 25(OH)D3 concentration, odds of AAA diagnosis was significantly reduced in both Queensland (adjusted odds ratio: 0.81; 95% confidence interval [CI]: 0.69-0.95; P = .009) and Western Australia (adjusted odds ratio: 0.80; 95% CI: 0.68-0.94; P = .005) cohorts. A subset of 310 eligible participants with small AAA from both regions were followed for a median of 4.2 (interquartile range: 2.0-5.8) years. Compared with vitamin D sufficient participants (50 to ˂75 nmol/L), annual mean AAA growth was significantly greater in those with higher vitamin D (≥75 nmol/L) (adjusted mean difference: 0.1 mm/y, 95% CI: 0.1-0.2; P < .001).CONCLUSIONS: High 25(OH)D3 concentration was paradoxically associated with a lower likelihood of AAA diagnosis and faster AAA growth. Further research is needed to resolve these conflicting findings.PMID:39219591 | PMC:PMC11362639 | DOI:10.1016/j.jvssci.2024.100208

Mol Med Rep. 2024 Nov;30(5):195. doi: 10.3892/mmr.2024.13319. Epub 2024 Sep 2.ABSTRACTPulmonary arterial hypertension (PAH) is a chronic and fatal disease characterized by pulmonary vascular remodeling, similar to the 'Warburg effect' observed in cancer, which is caused by reprogramming of glucose metabolism. Oroxylin A (OA), an active compound derived from Scutellaria baicalensis, which can inhibit glycolytic enzymes [hexokinase 2 (HK2), Lactate dehydrogenase (LDH), and pyruvate dehydrogenase kinase 1 (PDK1) by downregulating aerobic glycolysis to achieve the treatment of liver cancer. To the best of our knowledge, however, the impact of OA on PAH has not been addressed. Consequently, the present study aimed to evaluate the potential protective role and mechanism of OA against PAH induced by monocrotaline (MCT; 55 mg/kg). The mean pulmonary artery pressure (mPAP) was measured using the central venous catheter method; HE and Masson staining were used to observe pulmonary artery remodeling. Non‑targeted metabolomics was used to analyze the metabolic pathways and pathway metabolites in MCT‑PAH rats. Western Blot analysis was employed to assess the levels of glucose transporter 1 (Glut1), HK2), pyruvate kinase (PK), isocitrate dehydrogenase 2 (IDH2), pyruvate dehydrogenase kinase 1(PDK1), and lactate dehydrogenase (LDH) protein expression in both lung tissue samples from MCT‑PAH rats. The results demonstrated that intragastric administration of OA (40 and 80 mg/kg) significantly decreased mPAP from 43.61±1.88 mmHg in PAH model rats to 26.51±1.53 mmHg and relieve pulmonary artery remodeling. Untargeted metabolomic analysis and multivariate analysis indicated abnormal glucose metabolic pattern in PAH model rats, consistent with the Warburg effect. OA administration decreased this effect on the abnormal glucose metabolism. The protein levels of key enzymes involved in glucose metabolism were evaluated by western blotting, which demonstrated that OA could improve aerobic glycolysis and inhibit PAH by decreasing the protein levels of Glut1, HK2, LDH, PDK1 and increasing the protein levels of PK and IDH2. In conclusion, OA decreased MCT‑induced PAH in rats by reducing the Warburg effect.PMID:39219283 | DOI:10.3892/mmr.2024.13319

Oncol Rep. 2024 Oct;52(4):141. doi: 10.3892/or.2024.8800. Epub 2024 Sep 2.ABSTRACTHead and neck squamous cell carcinomas (HNSCCs), a heterogeneous group of cancers that arise from the mucosal epithelia cells in the head and neck areas, present great challenges in diagnosis, treatment and prognosis due to their complex aetiology and various clinical manifestations. Several factors, including smoking, alcohol consumption, oncogenic genes, growth factors, Epstein‑Barr virus and human papillomavirus infections can contribute to HNSCC development. The unpredictable tumour microenvironment adds to the complexity of managing HNSCC. Despite significant advances in therapies, the prediction of outcome after treatment for patients with HNSCC remains poor, and the 5‑year overall survival rate is low due to late diagnosis. Early detection greatly increases the chances of successful treatment. The present review aimed to bring together the latest findings related to the molecular mechanisms of HNSCC carcinogenesis and progression. Comprehensive genomic, transcriptomic, metabolomic, microbiome and proteomic analyses allow researchers to identify important biological markers such as genetic alterations, gene expression signatures and protein markers that drive HNSCC tumours. These biomarkers associated with the stages of initiation, progression and metastasis of cancer are useful in the management of patients with cancer in order to improve their life expectancy and quality of life.PMID:39219259 | DOI:10.3892/or.2024.8800