Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Evaluating cardiovascular risk in metabolic steatosis with precision medicine non-invasive approaches: insights from a cohort study

Thu, 16/05/2024 - 12:00
Intern Emerg Med. 2024 May 16. doi: 10.1007/s11739-024-03626-3. Online ahead of print.ABSTRACTMetabolic associated steatotic liver disease (MASLD) is the most common liver condition. It is associated with increased liver-related morbidity and mortality, and also with high risk of cardiovascular events (CVD), representing itself an independent risk factor for it. This makes MASLD a presentation of high interest for internal medicine, also because of its association with metabolic syndrome (MetS). It is crucial to assess its risks in a noninvasive way. With the aim of finding specific risk profiles for CVD development in MASLD by performing a noninvasive assessment of: (1) preclinical signs of endothelial dysfunction (ED); (2) clinical assessment of CVD risk by Framingham Heart Risk Score (FHRs); (3) genomic characterization of MASLD associated polymorphisms; (4) specific untargeted metabolomic profiles, we enrolled 466 MASLD patients non-invasively classified in 4 group of liver fibrosis severity (group-A: low-fibrosis risk, group-B: high-fibrosis risk, group-C: MASLD-cirrhosis, group-D: MASLD-HCC) and 73 healthy controls. FHRs was similar in controls and low-fibrosis group and significantly higher in high-fibrosis patients, cirrhosis, and HCC, increasing among classes. At a multivariable regression, FHRs was associated with liver disease severity and diabetes. 38.2% of patients had altered EndoPAT, resembling ED. Patients with high FHRs (> 40%) and ED had different metabolomics compared to those without ED. Our study reveals that a deep, non-invasive characterization of MASLD patients through precision medicine approaches (untargeted metabolomics, SNPs, ED assessment) was able to show a peculiar pattern in MASLD patients with increased CVD risk, mostly correlated with liver disease severity.PMID:38753115 | DOI:10.1007/s11739-024-03626-3

Dietary Flavonoid Quercetin Supplement Promotes Antiviral Innate Responses Against Vesicular Stomatitis Virus Infection by Reshaping the Bacteriome and Host Metabolome in Mice

Thu, 16/05/2024 - 12:00
Mol Nutr Food Res. 2024 May 16:e2300898. doi: 10.1002/mnfr.202300898. Online ahead of print.ABSTRACTSCOPE: Active ingredients in functional foods exhibit broad-spectrum antiviral activity. The objective of this study is to investigate the protective effect of quercetin derived from bee propolis, a natural product with antiviral activity and modulating effects on the gut microbiota, against vesicular stomatitis virus (VSV) infection.METHODS AND RESULTS: Through a cellular-based study, this study demonstrates that quercetin can modulate the activity of interferon-regulating factor 3 (IRF3). In vivo, it shows that quercetin protects mice from VSV infection by enhancing interferon production and inhibiting the production of proinflammatory cytokines. The study conducts 16S rRNA-based gut microbiota and nontargets metabolomics analyses to elucidate the mechanisms underlying quercetin-mediated bidirectional communication between the gut microbiome and host metabolome during viral infection. Quercetin not only ameliorates VSV-induced dysbiosis of the intestinal flora but also alters serum metabolites related to lipid metabolism. Cross-correlations between the gut bacteriome and the serum metabolome indicate that quercetin can modulate phosphatidylcholine (16:0/0:0) and 5-acetylamino-6-formylamino-3-methyluracil to prevent VSV infection.CONCLUSION: This study systematically elucidates the anti-VSV mechanism of quercetin through gut bacteriome and host metabolome assays, offering new insights into VSV treatment and revealing the mechanisms behind a novel disease management strategy using dietary flavonoid supplements.PMID:38752791 | DOI:10.1002/mnfr.202300898

Metabolic Pathways of Acylcarnitine Synthesis

Thu, 16/05/2024 - 12:00
Physiol Res. 2024 May 15. Online ahead of print.ABSTRACTAcylcarnitines are important markers in metabolic studies of many diseases, including metabolic, cardiovascular, and neurological disorders. We reviewed analytical methods for analyzing acylcarnitines with respect to the available molecular structural information, the technical limitations of legacy methods, and the potential of new mass spectrometry-based techniques to provide new information on metabolite structure. We summarized the nomenclature of acylcarnitines based on historical common names and common abbreviations, and we propose the use of systematic abbreviations derived from the shorthand notation for lipid structures. The transition to systematic nomenclature will facilitate acylcarnitine annotation, reporting, and standardization in metabolomics. We have reviewed the metabolic origins of acylcarnitines important for the biological interpretation of human metabolomic profiles. We identified neglected isomers of acylcarnitines and summarized the metabolic pathways involved in the synthesis and degradation of acylcarnitines, including branched-chain lipids and amino acids. We reviewed the primary literature, mapped the metabolic transformations of acyl-CoAs to acylcarnitines, and created a freely available WikiPathway WP5423 to help researchers navigate the acylcarnitine field. The WikiPathway was curated, metabolites and metabolic reactions were annotated, and references were included. We also provide a table for conversion between common names and abbreviations and systematic abbreviations linked to the LIPID MAPS or Human Metabolome Database.PMID:38752770

Offline Two-Dimensional Liquid Chromatography-Mass Spectrometry for Deep Annotation of the Fecal Metabolome Following Fecal Microbiota Transplantation

Thu, 16/05/2024 - 12:00
J Proteome Res. 2024 May 16. doi: 10.1021/acs.jproteome.4c00022. Online ahead of print.ABSTRACTBiological interpretation of untargeted LC-MS-based metabolomics data depends on accurate compound identification, but current techniques fall short of identifying most features that can be detected. The human fecal metabolome is complex, variable, incompletely annotated, and serves as an ideal matrix to evaluate novel compound identification methods. We devised an experimental strategy for compound annotation using multidimensional chromatography and semiautomated feature alignment and applied these methods to study the fecal metabolome in the context of fecal microbiota transplantation (FMT) for recurrent C. difficile infection. Pooled fecal samples were fractionated using semipreparative liquid chromatography and analyzed by an orthogonal LC-MS/MS method. The resulting spectra were searched against commercial, public, and local spectral libraries, and annotations were vetted using retention time alignment and prediction. Multidimensional chromatography yielded more than a 2-fold improvement in identified compounds compared to conventional LC-MS/MS and successfully identified several rare and previously unreported compounds, including novel fatty-acid conjugated bile acid species. Using an automated software-based feature alignment strategy, most metabolites identified by the new approach could be matched to features that were detected but not identified in single-dimensional LC-MS/MS data. Overall, our approach represents a powerful strategy to enhance compound identification and biological insight from untargeted metabolomics data.PMID:38752739 | DOI:10.1021/acs.jproteome.4c00022

Dysregulation of Gut Microbiota-Derived Neuromodulatory Amino Acid Metabolism in Human Immunodeficiency Virus-Associated Neurocognitive Disorder: An Integrative Metagenomic and Metabolomic Analysis

Thu, 16/05/2024 - 12:00
Ann Neurol. 2024 May 16. doi: 10.1002/ana.26963. Online ahead of print.ABSTRACTOBJECTIVE: Although accumulating evidence implicating altered gut microbiota in human immunodeficiency virus (HIV) infection and neurodegenerative disorders; however, the association between dysbiosis of the gut microbiota and metabolites in the pathogenesis of HIV-associated neurocognitive disorder (HAND) remains unclear.METHODS: Fecal and plasma samples were obtained from 3 cohorts (HAND, HIV-non-HAND, and healthy controls), metagenomic analysis and metabolomic profiling were performed to investigate alterations in the gut microbial composition and circulating metabolites in HAND.RESULTS: The gut microbiota of people living with HIV (PLWH) had an increased relative abundance of Prevotella and a decreased relative abundance of Bacteroides. In contrast, Prevotella and Megamonas were substantially decreased, and Bacteroides and Phocaeicola were increased in HAND patients. Moreover, untargeted metabolomics identified several neurotransmitters and certain amino acids associated with neuromodulation, and the differential metabolic pathways of amino acids associated with neurocognition were depleted in HAND patients. Notably, most neuromodulatory metabolites are associated with an altered abundance of specific gut bacteria.INTERPRETATION: Our findings provide new insights into the intricate interplay between the gut and microbiome-brain axis in the pathogenesis of HAND, highlighting the potential for developing novel therapeutic strategies that specifically target the gut microbiota. ANN NEUROL 2024.PMID:38752697 | DOI:10.1002/ana.26963

Transcutaneous vagus nerve stimulation modulates depression-like phenotype induced by high-fat diet via P2X7R/NLRP3/IL-1β in the prefrontal cortex

Thu, 16/05/2024 - 12:00
CNS Neurosci Ther. 2024 May;30(5):e14755. doi: 10.1111/cns.14755.ABSTRACTBACKGROUND: Depression is a common psychiatric disorder in diabetic patients. Depressive mood associated with obesity/metabolic disorders is related to the inflammatory response caused by long-term consumption of high-fat diets, but its molecular mechanism is unclear. In this study, we investigated whether the antidepressant effect of transcutaneous auricular vagus nerve stimulation (taVNS) in high-fat diet rats works through the P2X7R/NLRP3/IL-1β pathway.METHODS: We first used 16S rRNA gene sequencing analysis and LC-MS metabolomics assays in Zucker diabetic fatty (ZDF) rats with long-term high-fat diet (Purina #5008) induced significant depression-like behaviors. Next, the forced swimming test (FST) and open field test (OFT) were measured to evaluate the antidepressive effect of taVNS. Immunofluorescence and western blotting (WB) were used to measure the microglia state and the expression of P2X7R, NLRP3, and IL-1β in PFC.RESULTS: Purina#5008 diet induced significant depression-like behaviors in ZDF rats and was closely related to purine and inflammatory metabolites. Consecutive taVNS increased plasma insulin concentration, reduced glycated hemoglobin and glucagon content in ZDF rats, significantly improved the depressive-like phenotype in ZDF rats through reducing the microglia activity, and increased the expression of P2X7R, NLRP3, and IL-1β in the prefrontal cortex (PFC).CONCLUSION: The P2X7R/NLRP3/IL-1β signaling pathway may play an important role in the antidepressant-like behavior of taVNS, which provides a promising mechanism for taVNS clinical treatment of diabetes combined with depression.PMID:38752512 | DOI:10.1111/cns.14755

Chemical characterization and comparative analysis of different parts of <em>Cocculus orbiculatus</em> through UHPLC-Q-TOF-MS

Thu, 16/05/2024 - 12:00
Anal Methods. 2024 May 16. doi: 10.1039/d3ay02251j. Online ahead of print.ABSTRACTCocculus orbiculatus (L.) DC. (C. orbiculatus) is a medicinal herb valued for its dried roots with anti-inflammatory, analgesic, diuretic, and other therapeutic properties. Despite its traditional applications, chemical investigations into C. orbiculatus remain limited, focusing predominantly on alkaloids and flavonoids. Furthermore, the therapeutic use of C. orbiculatus predominantly focuses on the roots, leaving the stems, a significant portion of the plant, underutilized. This study employed ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) with in-house and online databases for comprehensive identification of components in various plant parts. Subsequently, untargeted metabolomics was employed to analyze differences in components across different harvest periods and plant sections of C. orbiculatus, aiming to screen for distinct components in different parts of the plant. Finally, metabolomic analysis of the roots and stems, which contribute significantly to the plant's weight, was conducted using chemometrics, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), orthogonal partial least squares discriminant analysis (OPLS-DA), and heatmaps. A total of 113 components, including alkaloids, flavonoids, and organic acids, were annotated across the root, stem, leaf, flower, and fruit, along with numerous previously unreported compounds. Metabolomic analyses revealed substantial differences in components between the root and stem compared to the leaf, flower, and fruit during the same harvest period. PLS-DA and OPLS-DA annotated 10 differentiating components (VIP > 1.5, P < 0.05, FC > 2 or FC < 0.67), with 5 unique to the root and stem, exhibiting lower mass spectrometric responses. This study provided the first characterization of 113 chemical constituents in different parts of C. orbiculatus, laying the groundwork for pharmacological research and advocating for the enhanced utilization of its stem.PMID:38752456 | DOI:10.1039/d3ay02251j

Metabolic trajectories of diabetic ketoacidosis onset described by breath analysis

Thu, 16/05/2024 - 12:00
Front Endocrinol (Lausanne). 2024 May 1;15:1360989. doi: 10.3389/fendo.2024.1360989. eCollection 2024.ABSTRACTPURPOSE: This feasibility study aimed to investigate the use of exhaled breath analysis to capture and quantify relative changes of metabolites during resolution of acute diabetic ketoacidosis under insulin and rehydration therapy.METHODS: Breath analysis was conducted on 30 patients of which 5 with DKA. They inflated Nalophan bags, and their metabolic content was subsequently interrogated by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS).RESULTS: SESI-HRMS analysis showed that acetone, pyruvate, and acetoacetate, which are well known to be altered in DKA, were readily detectable in breath of participants with DKA. In addition, a total of 665 mass spectral features were found to significantly correlate with base excess and prompt metabolic trajectories toward an in-control state as they progress toward homeostasis.CONCLUSION: This study provides proof-of-principle for using exhaled breath analysis in a real ICU setting for DKA monitoring. This non-invasive new technology provides new insights and a more comprehensive overview of the effect of insulin and rehydration during DKA treatment.PMID:38752172 | PMC:PMC11094216 | DOI:10.3389/fendo.2024.1360989

Impact of preovulatory follicle maturity on oocyte metabolism and embryo development

Thu, 16/05/2024 - 12:00
PNAS Nexus. 2024 Apr 30;3(5):pgae181. doi: 10.1093/pnasnexus/pgae181. eCollection 2024 May.ABSTRACTImproved oocyte competence for embryo development and pregnancy was observed following ovulation of preovulatory follicles with greater physiological maturity, as indicated by estradiol production, prior to the gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) surge. It was hypothesized that follicular fluid from preovulatory follicles of greater maturity better supports the maturing oocyte's metabolic requirements and improves embryo development. The objective was to determine if differences in preovulatory follicular fluid due to follicle maturity influence oocyte metabolism during in vitro maturation (IVM) and affect embryo development. Bovine preovulatory follicular fluid was collected 18 h after a GnRH-induced LH surge. Serum estradiol concentration at GnRH administration categorized follicles as greater or lesser maturity. Immature bovine oocytes were submitted to 24 h IVM in medium supplemented with 20% follicular fluid from preovulatory follicles of greater or lesser maturity. Embryo development was recorded. Oocyte maturation media and media conditioned by developing embryos were submitted for metabolomics. A randomized block design was utilized to determine differences in embryo development and media metabolites (P ≤ 0.05). Blastocysts from oocytes matured in greater vs. lesser maturity follicular fluid had a more moderate rate of development (P = 0.01). At the conclusion of 24 h IVM, abundance of 66 metabolites differed between greater and lesser follicle maturity treatments. Nine metabolites differed in media conditioned by developing embryos. Metabolome results suggest improved amino acid, purine, and glucose metabolism, followed by a more efficient rate of embryo development, in oocytes matured in greater vs lesser maturity follicular fluid.PMID:38752021 | PMC:PMC11095542 | DOI:10.1093/pnasnexus/pgae181

Unveiling the regulatory mechanism of poly-gamma-glutamic acid on soil characteristics under drought stress through integrated metagenomics and metabolomics analysis

Thu, 16/05/2024 - 12:00
Front Microbiol. 2024 May 1;15:1387223. doi: 10.3389/fmicb.2024.1387223. eCollection 2024.ABSTRACTIt is of utmost importance to understand the characteristics and regulatory mechanisms of soil in order to optimize soil management and enhance crop yield. Poly-γ-glutamic acid (γ-PGA), a stress-resistant amino acid polymer, plays a crucial role in plant drought stress resistance. However, little is known about the effects of γ-PGA on soil characteristics during drought treatments. In this study, the effects of different forms of γ-PGA on soil texture and basic physical and chemical properties under short-term drought conditions were investigated. Furthermore, the impact of γ-PGA on the microbial community and metabolic function of maize was analyzed. Under drought conditions, the introduction of γ-PGA into the soil resulted in notable improvements in the mechanical composition ratio and infiltration capacity of the soil. Concurrently, this led to a reduction in soil bulk density and improved soil organic matter content and fertility. Additionally, metagenomic analysis revealed that under drought conditions, the incorporation of γ-PGA into the soil enhanced the soil microbiota structure. This shift led to the predominance of bacteria that are crucial for carbon, nitrogen, and phosphorus cycles in the soil. Metabolomics analysis revealed that under drought treatment, γ-PGA affected soil metabolic patterns, with a particular focus on alterations in amino acid and vitamin metabolism pathways. Correlation analysis between the soil metagenome and metabolites showed that microorganisms played a significant role in metabolite accumulation. These results demonstrated that γ-PGA could improve soil characteristics under drought conditions and play an important role in soil microorganisms and microbial metabolism, providing further insights into the changes in soil characteristics under drought conditions.PMID:38751715 | PMC:PMC11094619 | DOI:10.3389/fmicb.2024.1387223

Metabolomics combined with mathematical analysis reveals metabolic pathways specific to metastatic cancers

Thu, 16/05/2024 - 12:00
Transl Breast Cancer Res. 2024 Apr 25;5:15. doi: 10.21037/tbcr-23-51. eCollection 2024.NO ABSTRACTPMID:38751674 | PMC:PMC11093075 | DOI:10.21037/tbcr-23-51

Anti-MRSA mechanism of spirostane saponin in Rohdea pachynema F.T.Wang &amp; Tang

Thu, 16/05/2024 - 12:00
J Ethnopharmacol. 2024 May 13:118327. doi: 10.1016/j.jep.2024.118327. Online ahead of print.ABSTRACTETHNOPHARMACOLOGY RELEVANCE: Rohdea pachynema F.T.Wang & Tang (R. pachynema), is a traditional folk medicine used for the treatment of stomach pain, stomach ulcers, bruises, and skin infections in China. Some of the diseases may relate to microbial infections in traditional applications. However few reports on its antimicrobial properties and bioactive components.AIM OF THE STUDY: To identify its bioactive constituents against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo, and its mechanism.MATERIALS AND METHODS: The anti-MRSA ingredient 6α-O-[β-D-xylopyranosyl-(1→3)-β-D-quinovopyranosyl]-(25S)-5α-spirostan-3β-ol (XQS) was obtained from R. pachynema by phytochemical isolation. Subsequently, XQS underwent screening using the broth microdilution method and growth inhibition curves to assess its antibacterial activity. The mechanism of XQS was evaluated by multigeneration induction, biofilm resistance assay, scanning electron microscopy, transmission electron microscopy, and metabolomics. Additionally, a mouse skin infection model was established in vivo.RESULTS: 26 compounds were identified from the R. pachynema, in which anti-MRSA spirostane saponin (XQS) was reported for the first time with a minimum inhibitory concentration (MIC) of 8 μg/mL. XQS might bind to peptidoglycan (PGN) of the cell wall, phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) of the cell membrane, then destroying the cell wall and the cell membrane, resulting in reduced membrane fluidity and membrane depolarization. Furthermore, XQS affected MRSA lipid metabolism, amino acid metabolism, and ABC transporters by metabolomics analysis, which targeted cell walls and membranes causing less susceptibility to drug resistance. Furthermore, XQS (8 mg/kg) recovered skin wounds in mice infected by MRSA effectively, superior to vancomycin (8 mg/kg).CONCLUSIONS: XQS showed anti-MRSA bioactivity in vitro and in vivo, and its mechanism association with cell walls and membranes was reported for the first, which supported the traditional uses of R. pachynema and explained its sensitivity to MRSA.PMID:38750987 | DOI:10.1016/j.jep.2024.118327

Single-cell technologies in psoriasis

Thu, 16/05/2024 - 12:00
Clin Immunol. 2024 May 13:110242. doi: 10.1016/j.clim.2024.110242. Online ahead of print.ABSTRACTPsoriasis is a chronic and recurrent inflammatory skin disorder. The primary manifestation of psoriasis arises from disturbances in the cutaneous immune microenvironment, but the specific functions of the cellular components within this microenvironment remain unknown. Recent advancements in single-cell technologies have enabled the detection of multi-omics at the level of individual cells, including single-cell transcriptome, proteome, and metabolome, which have been successfully applied in studying autoimmune diseases, and other pathologies. These techniques allow the identification of heterogeneous cell clusters and their varying contributions to disease development. Considering the immunological traits of psoriasis, an in-depth exploration of immune cells and their interactions with cutaneous parenchymal cells can markedly advance our comprehension of the mechanisms underlying the onset and recurrence of psoriasis. In this comprehensive review, we present an overview of recent applications of single-cell technologies in psoriasis, aiming to improve our understanding of the underlying mechanisms of this disorder.PMID:38750947 | DOI:10.1016/j.clim.2024.110242

Surgery for Crohn's Disease Is Associated with a Dysbiotic Microbiome and Metabolome: Results from Two Prospective Cohorts

Thu, 16/05/2024 - 12:00
Cell Mol Gastroenterol Hepatol. 2024 May 13:S2352-345X(24)00111-5. doi: 10.1016/j.jcmgh.2024.05.005. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Crohn's disease is associated with alterations in the gut microbiome and metabolome described as dysbiosis. We characterized the microbial and metabolic consequences of ileal resection, the most common Crohn's disease surgery.METHODS: Patients with and without intestinal resection were identified from the Diet to Induce Remission in Crohn's Disease and Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease studies. Stool samples were analyzed with shotgun metagenomics sequencing. Fecal butyrate was measured with 1H nuclear magnetic resonance spectroscopy. Fecal bile acids and plasma 7α-hydroxy-4-cholesten-3-one (C4) was measured with mass spectrometry.RESULTS: Intestinal resection was associated with reduced alpha diversity and altered beta diversity with increased Proteobacteria and reduced Bacteroidetes and Firmicutes. Surgery was associated with higher representation of genes in the KEGG pathway for ABC transporters and reduction in genes related to bacterial metabolism. Surgery was associated with reduced concentration of the But gene but this did not translate to reduced fecal butyrate concentration. Surgery was associated with decreased abundance of bai operon genes, with increased plasma C4 concentration, increased primary bile acids and reduced secondary bile acids, including isoLCA. Additionally, E lenta, A equalofaciens and G pamelaeae were lower in abundance among patients with prior surgery in both cohorts.CONCLUSIONS: In two different populations, prior surgery in Crohn's disease is associated with altered fecal microbiome. Patients who had undergone ileal resection had reduction in the potentially beneficial bacteria E lenta and related actinobacteria as well as secondary bile acids, including isoLCA, suggesting that these could be biomarkers of patients at higher risk for disease progression.PMID:38750900 | DOI:10.1016/j.jcmgh.2024.05.005

Targeted metabolomics and transcript profiling of methyltransferases in three coffee species

Thu, 16/05/2024 - 12:00
Plant Sci. 2024 May 13:112117. doi: 10.1016/j.plantsci.2024.112117. Online ahead of print.ABSTRACTCoffee plants contain well-known xanthines as caffeine. Three Coffea species grown in a controlled greenhouse environment were the focus of this research. Coffea arabica and C. canephora are two first principal commercial species and commonly known as arabica and robusta, respectively. Originating in Central Africa, C. anthonyi is a novel species with small leaves. The xanthine metabolites in flower, fruit and leaf extracts were compared using both targeted and untargeted metabolomics approaches. We evaluated how the xanthine derivatives and FQA isomers relate to the expression of biosynthetic genes encoding N- and O-methyltransferases. Theobromine built up in leaves of C. anthonyi because caffeine biosynthesis was hindered in the absence of synthase gene expression. Despite this, green fruits expressed these genes and they produced caffeine. Given that C. anthonyi evolved successfully over time, these findings put into question the defensive role of caffeine in leaves. An overview of the histolocalisation of xanthines in the different flower parts of Coffea arabica was also provided. The gynoecium contained more theobromine than the flower buds or petals. This could be attributed to increased caffeine biosynthesis before fructification. The presence of theophylline and the absence of theobromine in the petals indicate that caffeine is catabolized more in the petals than in the gynoecium.PMID:38750798 | DOI:10.1016/j.plantsci.2024.112117

Fatty acids metabolism in ozone-induced pulmonary inflammatory injury: Evidence, mechanism and prevention

Thu, 16/05/2024 - 12:00
Sci Total Environ. 2024 May 13:173222. doi: 10.1016/j.scitotenv.2024.173222. Online ahead of print.ABSTRACTOzone (O3) is a major air pollutant that directly threatens the respiratory system, lung fatty acid metabolism disorder is an important molecular event in pulmonary inflammatory diseases. Liver kinase B1 (LKB1) and nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome not only regulate inflammation, but also have close relationship with fatty acid metabolism. However, the role and mechanism of LKB1 and NLRP3 inflammasome in lung fatty acid metabolism, which may contribute to ozone-induced lung inflammation, remain unclear, and effective strategy for preventing O3-induced pulmonary inflammatory injury is lacking. To explore these, mice were exposed to 1.00 ppm O3 (3 h/d, 5 days), and pulmonary inflammation was determined by airway hyperresponsiveness, histopathological examination, total cells and cytokines in bronchoalveolar lavage fluid (BALF). Targeted fatty acids metabolomics was used to detect medium and long fatty acid in lung tissue. Then, using LKB1-overexpressing adenovirus and NLRP3 knockout (NLRP3-/-) mice to explore the mechanism of O3-induced lung fatty acid metabolism disorder. Results demonstrated that O3 exposure caused pulmonary inflammatory injury and lung medium and long chain fatty acids metabolism disorder, especially decreased dihomo-γ-linolenic acid (DGLA). Meanwhile, LKB1 expression was decreased, and NLRP3 inflammasome was activated in lung of mice after O3 exposure. Additionally, LKB1 overexpression alleviated O3-induced lung inflammation and inhibited the activation of NLRP3 inflammasome. And we found that pulmonary fatty acid metabolism disorder was ameliorated of NLRP3 -/- mice compared with those in wide type mice after O3 exposure. Furthermore, administrating DGLA intratracheally prior to O3 exposure significantly attenuated O3-induced pulmonary inflammatory injury. Taken together, these findings suggest that fatty acids metabolism disorder is involved in O3-induced pulmonary inflammation, which is regulated by LKB1-mediated NLRP3 pathway, DGLA supplement could be a useful preventive strategy to ameliorate ozone-associated lung inflammatory injury.PMID:38750750 | DOI:10.1016/j.scitotenv.2024.173222

Oceanobacillus picturae alleviates cadmium stress and promotes growth in soybean seedlings

Wed, 15/05/2024 - 12:00
J Hazard Mater. 2024 May 11;472:134568. doi: 10.1016/j.jhazmat.2024.134568. Online ahead of print.ABSTRACTCadmium (Cd) is a heavy metal that significantly impacts human health and the environment. Microorganisms play a crucial role in reducing heavy metal stress in plants; however, the mechanisms by which microorganisms enhance plant tolerance to Cd stress and the interplay between plants and microorganisms under such stress remain unclear. In this study, Oceanobacillus picturae (O. picturae) was isolated for interaction with soybean seedlings under Cd stress. Results indicated that Cd treatment alone markedly inhibited soybean seedling growth. Conversely, inoculation with O. picturae significantly improved growth indices such as plant height, root length, and fresh weight, while also promoting recovery in soil physiological indicators and pH. Metabolomic and transcriptomic analyses identified 157 genes related to aspartic acid, cysteine, and flavonoid biosynthesis pathways. Sixty-three microbial species were significantly associated with metabolites in these pathways, including pathogenic, adversity-resistant, and bioconductive bacteria. This research experimentally demonstrates, for the first time, the growth-promoting effect of the O. picturae strain on soybean seedlings under non-stress conditions. It also highlights its role in enhancing root growth and reducing Cd accumulation in the roots under Cd stress. Additionally, through the utilization of untargeted metabolomics, metagenomics, and transcriptomics for a multi-omics analysis, we investigated the impact of O. picturae on the soil microbiome and its correlation with differential gene expression in plants. This innovative approach unveils the molecular mechanisms underlying O. picturae's promotion of root growth and adaptation to Cd stress.PMID:38749246 | DOI:10.1016/j.jhazmat.2024.134568

Comprehensive insights into the effects of acidogenic off-gas utilization on successive biogas production, microbial community structure and metabolite distribution during two-stage anaerobic digestion

Wed, 15/05/2024 - 12:00
Water Res. 2024 May 8;258:121740. doi: 10.1016/j.watres.2024.121740. Online ahead of print.ABSTRACTAlthough two-stage anaerobic digestion (TSAD) technology has been investigated, the mechanisms regarding the impact of acidogenic off-gas (AOG) on successive methane production have not been well addressed. In this study, a novel TSAD system was designed. Food waste, as the main substrate, was co-digested with chicken manure and corn straw. The acidogenic gas beyond atmospheric pressure was introduced into the bottom of the methanogenesis reactor through a stainless steel diffuser. Results showed the addition of AOG increased the methane yield from 435.2 to 597.1 mL/g VSin in successive methanogenesis stage, improved by 37.2 %, and increased the energy yield from 9.0 to 11.3 kJ/g VSsubstrate. However, the theoretical contribution of hydrogenotrophic methanogenesis using H2 contained in AOG was only 15.2 % of the increased methane yield. After the addition of AOG, the decreased levels of ammonia nitrogen and butyrate indicate that the stability of the AD system was improved. The electron transfer system and co-enzyme F420 activity were enhanced; however, the decrease in acetate kinase activity indicates aceticlastic methanogenesis may have been weakened. The microbial diversity and species richness were improved by the added AOG. Methanosarcina was more competitive than Methanothermobacter, enhancing the syntrophic effect. The relative abundance of protein degradation bacteria norank_f_Anaerolineaceae and lipid degradation bacteria Syntrophomonas was increased. Metabolite analysis confirmed that the addition of AOG promoted amino acid metabolism, the biosynthesis of other secondary metabolism and lipid metabolism. The improved degradation of recalcitrant organic components (lipids and proteins) in food waste was responsible for the increased methane yield. This study provides an in-depth understanding of the impact of AOG utilization on successive methane production and has practical implications for the treatment of food waste.PMID:38749185 | DOI:10.1016/j.watres.2024.121740

The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury

Wed, 15/05/2024 - 12:00
Biomed Pharmacother. 2024 May 14;175:116730. doi: 10.1016/j.biopha.2024.116730. Online ahead of print.ABSTRACTAcute kidney injury (AKI) disrupts energy metabolism. Targeting metabolism through AMP-activated protein kinase (AMPK) may alleviate AKI. ATX-304, a pan-AMPK activator, was evaluated in C57Bl/6 mice and tubular epithelial cell (TEC) cultures. Mice received ATX-304 (1 mg/g) or control chow for 7 days before cisplatin-induced AKI (CI-AKI). Primary cultures of tubular epithelial cells (TECs) were pre-treated with ATX-304 (20 µM, 4 h) prior to exposure to cisplatin (20 µM, 23 h). ATX-304 increased acetyl-CoA carboxylase phosphorylation, indicating AMPK activation. It protected against CI-AKI measured by serum creatinine (control 0.05 + 0.03 mM vs ATX-304 0.02 + 0.01 mM, P = 0.03), western blot for neutrophil gelatinase-associated lipocalin (NGAL) (control 3.3 + 1.8-fold vs ATX-304 1.2 + 0.55-fold, P = 0.002), and histological injury (control 3.5 + 0.59 vs ATX-304 2.7 + 0.74, P = 0.03). In TECs, pre-treatment with ATX-304 protected against cisplatin-mediated injury, as measured by lactate dehydrogenase release, MTS cell viability, and cleaved caspase 3 expression. ATX-304 protection against cisplatin was lost in AMPK-null murine embryonic fibroblasts. Metabolomic analysis in TECs revealed that ATX-304 (20 µM, 4 h) altered 66/126 metabolites, including fatty acids, tricarboxylic acid cycle metabolites, and amino acids. Metabolic studies of live cells using the XFe96 Seahorse analyzer revealed that ATX-304 increased the basal TEC oxygen consumption rate by 38%, whereas maximal respiration was unchanged. Thus, ATX-304 protects against cisplatin-mediated kidney injury via AMPK-dependent metabolic reprogramming, revealing a promising therapeutic strategy for AKI.PMID:38749175 | DOI:10.1016/j.biopha.2024.116730

Blue revolution turning green? A global concern of cyanobacteria and cyanotoxins in freshwater aquaculture: A literature review

Wed, 15/05/2024 - 12:00
J Environ Manage. 2024 May 14;360:121115. doi: 10.1016/j.jenvman.2024.121115. Online ahead of print.ABSTRACTTo enhance productivity, aquaculture is intensifying, with high-density fish ponds and increased feed input, contributing to nutrient load and eutrophication. Climate change further exacerbates cyanobacterial blooms and cyanotoxin production that affect aquatic organisms and consumers. A review was conducted to outline this issue from its inception - eutrophication, cyanobacterial blooms, their harmful metabolites and consequential effects (health and economic) in aquacultures. The strength of evidence regarding the relationship between cyanobacteria/cyanotoxins and potential consequences in freshwater aquacultures (fish production) globally were assessed as well, while identifying knowledge gaps and suggesting future research directions. With that aim several online databases were searched through June 2023 (from 2000), and accessible publications conducted in aquacultures with organisms for human consumption, reflecting cyanotoxin exposure, were selected. Data on cyanobacteria/cyanotoxins in aquacultures and its products worldwide were extracted and analyzed. Selected 63 papers from 22 countries were conducted in Asia (48%), Africa (22%), America (22%) and Europe (8%). Microcystis aeruginosa was most frequent, among over 150 cyanobacterial species. Cyanobacterial metabolites (mostly microcystins) were found in aquaculture water and fish from 18 countries (42 and 33 papers respectively). The most affected were small and shallow fish ponds, and omnivorous or carnivorous fish species. Cyanotoxins were detected in various fish organs, including muscles, with levels exceeding the tolerable daily intake in 60% of the studies. The majority of research was done in developing countries, employing less precise detection methods, making the obtained values estimates. To assess the risk of human exposure, the precise levels of all cyanotoxins, not just microcystins are needed, including monitoring their fate in aquatic food chains and during food processing. Epidemiological research on health consequences, setting guideline values, and continuous monitoring are necessary as well. Further efforts should focus on methods for elimination, prevention, and education.PMID:38749125 | DOI:10.1016/j.jenvman.2024.121115

Pages