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

Elucidation of the effects of autochthonous starter on nitrogen-containing compounds during fermentation of <em>Yujiangsuan</em> by metabolomics

Mon, 18/12/2023 - 12:00
Food Sci Nutr. 2023 Oct 19;11(12):7546-7554. doi: 10.1002/fsn3.3674. eCollection 2023 Dec.ABSTRACTTo understand the role of microorganisms in nitrogen (N)-containing compound changes during the processing of Yujiangsuan by autochthonous starter cultures, the GC-TOF-MS-based metabolomics method was adopted to investigate the effects of Weissella cibaria and Lactobacillus plantarum. The results demonstrated that inoculation of autochthonous strains led to differential metabolites, such as fatty acids, organic oxygen compounds, and carboxylic acids on day 4 to day 12 of fermentation. The N-containing compounds under the inoculated fermentation group showed a faster relative concentration change. Nucleotide metabolism and arginine and proline metabolism exerted an influence on the formation of N-containing compounds. Apart from that, the effect of W. cibaria and L. plantarum on the hydrolysis of macromolecules was the main factor causing differences in major N-containing compounds.PMID:38107150 | PMC:PMC10724583 | DOI:10.1002/fsn3.3674

Effect of <em>Cichorium glandulosum</em> on intestinal microbiota and bile acid metabolism in db/db mice

Mon, 18/12/2023 - 12:00
Food Sci Nutr. 2023 Oct 25;11(12):7765-7778. doi: 10.1002/fsn3.3694. eCollection 2023 Dec.ABSTRACTThis study aims to investigate the effects of Chorum glandulosum Boiss. et Huet (CG) on the intestinal microbiota and serum bile acid (BA) in db/db mice. A total of 12 db/db mice were randomly divided into model (MOD), high-dose CG (CGH), and control (CON) groups. The CON and MOD groups received distilled water by gavage for 8 weeks. Whereas, the CGH group received an alcohol extract of CG at a dose of 200 mg/kg/day. Results showed that CG can reduce blood lipid levels. It change the composition of the intestinal microbiota, and increase the relative abundances of Muribaculaceae, Prevotellaceae, Bifidobacterium_pseudolongum, Bacteroidaceae in db/db mice as well. LC-MS metabolomics results showed that CG adjusted the serum BA levels. The results reduced the levels of primary BAs, such as cholic acid (CA) and chenodeoxycholic acid (CDCA). The results decreased the primary BA/secondary BA (PSA/SBA) ratio in db/db mice. Correlation analysis showed that the abundances of Bifidobacterium_pseudolongum and Bacteroidaceae were positively correlated with acetic acid level and negatively correlated with ursocholic acid (UCA), α-muricholic acid (αMCA), triglyceride (TG), and total cholesterol levels (TC), indicating an interaction between the intestinal microbiota and serum BAs. CG may play a positive role in the interaction between the intestinal microbiota and BAs in lipid metabolism.PMID:38107125 | PMC:PMC10724598 | DOI:10.1002/fsn3.3694

Naringenin prevents non-alcoholic steatohepatitis by modulating the host metabolome and intestinal microbiome in MCD diet-fed mice

Mon, 18/12/2023 - 12:00
Food Sci Nutr. 2023 Sep 27;11(12):7826-7840. doi: 10.1002/fsn3.3700. eCollection 2023 Dec.ABSTRACTNon-alcoholic steatohepatitis (NASH) is a severe inflammatory phase of the non-alcoholic fatty liver disease (NAFLD) spectrum and can progress to advanced stages of NAFLD if left untreated. This study uses multi-omics data to elucidate the underlying mechanism of naringenin's reported benefit in alleviating (NASH). Male mice were fed a NASH-inducing (methionine-choline-deficient) MCD diet with or without naringenin supplementation for 6 weeks. Naringenin prevented NASH-induced histopathological liver damage and reversed the abnormal levels of hepatic triglyceride (TG)/total cholesterol (TC), serum TG/TC, serum alanine aminotransferase/aspartate transaminase, and hepatic malondialdehyde and glutathione. Importantly, naringenin intervention significantly modulated the relative abundance of gut microbiota and the host metabolomic profile. We detected more than 700 metabolites in the serum and found that the gut genus levels of Anaeroplasma and the [Eubacterium] nodatum group were closely associated with xanthine, 2-picoline, and securinine, respectively. Tuzzerella alterations showed the highest number of associations with host endogenous metabolites such as FAHFA (8:0/10:0), FFA (20:2), carnitine C8:1, tridecanedioic acid, securinine, acetylvaline, DL-O-tyrosine, and Phe-Asn. This study indicates that the interplay between host serum metabolites and gut microbiota may contribute to the therapeutic effect of naringenin against NASH.PMID:38107095 | PMC:PMC10724642 | DOI:10.1002/fsn3.3700

Development of a Green Single Drop Microextraction Based on Deep Eutectic Solvent and HPLC-UV for Trace Residue Analysis of Three Frequent-Used Pesticides

Mon, 18/12/2023 - 12:00
Iran J Public Health. 2023 Nov;52(11):2440-2449. doi: 10.18502/ijph.v52i11.14043.ABSTRACTBACKGROUND: A green sample preparation method named deep eutectic solvent-based single drop microextraction (DES-SDME) was developed and optimized for determining trace metribuzin, dichlorvos, and fenthion.METHODS: Two hundred seventy experimental runs were performed, and the optimal values of the five influential factors in the DES-SDME method were determined. The design of the study was based on one factor at a time and the peak area of high-performance liquid chromatography was used as a benchmark for comparing analysis results.RESULTS: After optimizing the effective factors, the linearity range, detection limit and quantification limit of the method were determined by drawing calibration curves for the studied analytes.CONCLUSION: The results indicated the success of the developed method in obtaining acceptable figures of merit as a green preparation method with accuracy and precision.PMID:38106827 | PMC:PMC10719709 | DOI:10.18502/ijph.v52i11.14043

Arginine Biosynthesis Pathway Found to Play a Key Role in the Neuroprotective Effect of Liu-Wei-Luo-Bi (LWLB) Granules in Diabetic db/db Mice with Peripheral Neuropathy Using an Untargeted Metabolomics Strategy

Mon, 18/12/2023 - 12:00
Diabetes Metab Syndr Obes. 2023 Dec 11;16:4065-4080. doi: 10.2147/DMSO.S423388. eCollection 2023.ABSTRACTAIM: Liu-Wei-Luo-Bi (LWLB) granules was a Chinese compound prescription for treating diabetic peripheral neuropathy (DPN). The aim of this study was to investigate the effect of LWLB granules on diabetic mice with peripheral neuropathy and to elucidate the potential mechanism based on an untargeted metabolomics approach.METHODS: One hundred forty db/db mice were randomly divided into seven groups: the Control group, DPN group, Mudan (MD) granules group, Epalrestat (Epa) group, and the LWLB low, medium, or high dose (LW-l, LW-m, or LW-h) group. After 12 weeks of treatment, body weight, blood glucose, mechanical pain threshold, motor conduction velocity (MCV), sensory conduction velocity (SCV), and Pathological Organization of the Sciatic and Caudal Nerves in mice were measured. Serum samples were collected for untargeted metabolomics analysis using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and multivariate statistics. Disease-related pathways were screened out with function enrichment analyses of candidate biomarkers.RESULTS: LWLB granules can improve the peripheral neuropathy of type 2 diabetic mice with peripheral nerve conduction disorders, mainly through significantly improving the nerve conduction velocity (P < 0.05) and lowering the mechanical pain threshold (P < 0.05). A total of 43 metabolites were identified as potential biomarkers related to the therapeutic effect of LWLB granules. Fifty, 4, and 26; 23, 4, and 22; and 24, 1, and 16 biomarkers were discovered in the LW-l, LW-m, and LW-h groups at the 4th, 6th, and 12th weeks, respectively. Five, three, seven, five, and four metabolic pathways were found in MD, Epa, LW-l, LW-m, and LW-h groups, respectively. The arginine biosynthesis pathway is the overlapping pathway in LW-l, LW-m, and LW-h groups.CONCLUSION: LWLB granules have an obvious neuroprotective effect on diabetic peripheral neuropathy, and the metabolism mechanism of LWLB is mainly related to the arginine biosynthesis pathway on diabetic db/db mice with peripheral neuropathy.PMID:38106622 | PMC:PMC10723181 | DOI:10.2147/DMSO.S423388

Dietary restriction of individual amino acids stimulates unique molecular responses in mouse liver

Mon, 18/12/2023 - 12:00
bioRxiv. 2023 Dec 7:2023.12.06.570456. doi: 10.1101/2023.12.06.570456. Preprint.ABSTRACTDietary protein and essential amino acid (EAA) restriction promotes favorable metabolic reprogramming, ultimately resulting in improvements to both health and lifespan. However, as individual EAAs have distinct catabolites and engage diverse downstream signaling pathways, it remains unclear to what extent shared or AA-specific molecular mechanisms promote diet-associated phenotypes. Here, we investigated the physiological and molecular effects of restricting either dietary methionine, leucine, or isoleucine (Met-R, Leu-R, and Ile-R) for 3 weeks in C57BL/6J male mice. While all 3 AA-depleted diets promoted fat and lean mass loss and slightly improved glucose tolerance, the molecular responses were more diverse; while hepatic metabolites altered by Met-R and Leu-R were highly similar, Ile-R led to dramatic changes in metabolites, including a 3-fold reduction in the oncometabolite 2-hydroxyglutarate. Pathways regulated in an EAA-specific manner included glycolysis, the pentose phosphate pathway (PPP), nucleotide metabolism, the TCA cycle and amino acid metabolism. Transcriptiome analysis and global profiling of histone post-translational modifications (PTMs) revealed different patterns of responses to each diet, although Met-R and Leu-R again shared similar transcriptional responses. While the pattern of global histone PTMs were largely unique for each dietary intervention, Met-R and Ile-R had similar changes in histone-3 methylation/acetylation PTMs at lysine-9. Few similarities were observed between the physiological or molecular responses to EAA restriction and treatment with rapamycin, an inhibitor of the mTORC1 AA-responsive protein kinase, indicating the response to EAA restriction may be largely independent of mTORC1. Together, these results demonstrate that dietary restriction of individual EAAs has unique, EAA-specific effects on the hepatic metabolome, epigenome, and transcriptome, and suggests that the specific EAAs present in dietary protein may play a key role at regulating health at the molecular level.PMID:38106163 | PMC:PMC10723491 | DOI:10.1101/2023.12.06.570456

GeneMAP: A discovery platform for metabolic gene function

Mon, 18/12/2023 - 12:00
bioRxiv. 2023 Dec 8:2023.12.07.570588. doi: 10.1101/2023.12.07.570588. Preprint.ABSTRACTOrganisms maintain metabolic homeostasis through the combined functions of small molecule transporters and enzymes. While many of the metabolic components have been well-established, a substantial number remains without identified physiological substrates. To bridge this gap, we have leveraged large-scale plasma metabolome genome-wide association studies (GWAS) to develop a multiomic Gene-Metabolite Associations Prediction (GeneMAP) discovery platform. GeneMAP can generate accurate predictions, even pinpointing genes that are distant from the variants implicated by GWAS. In particular, our work identified SLC25A48 as a genetic determinant of plasma choline levels. Mechanistically, SLC25A48 loss strongly impairs mitochondrial choline import and synthesis of its downstream metabolite, betaine. Rare variant testing and polygenic risk score analyses have elucidated choline-relevant phenomic consequences of SLC25A48 dysfunction. Altogether, our study proposes SLC25A48 as a mitochondrial choline transporter and provides a discovery platform for metabolic gene function.PMID:38106122 | PMC:PMC10723489 | DOI:10.1101/2023.12.07.570588

Inferring Metabolic States from Single Cell Transcriptomic Data via Geometric Deep Learning

Mon, 18/12/2023 - 12:00
bioRxiv. 2023 Dec 7:2023.12.05.570153. doi: 10.1101/2023.12.05.570153. Preprint.ABSTRACTThe ability to measure gene expression at single-cell resolution has elevated our understanding of how biological features emerge from complex and interdependent networks at molecular, cellular, and tissue scales. As technologies have evolved that complement scRNAseq measurements with things like single-cell proteomic, epigenomic, and genomic information, it becomes increasingly apparent how much biology exists as a product of multimodal regulation. Biological processes such as transcription, translation, and post-translational or epigenetic modification impose both energetic and specific molecular demands on a cell and are therefore implicitly constrained by the metabolic state of the cell. While metabolomics is crucial for defining a holistic model of any biological process, the chemical heterogeneity of the metabolome makes it particularly difficult to measure, and technologies capable of doing this at single-cell resolution are far behind other multiomics modalities. To address these challenges, we present GEFMAP (Gene Expression-based Flux Mapping and Metabolic Pathway Prediction), a method based on geometric deep learning for predicting flux through reactions in a global metabolic network using transcriptomics data, which we ultimately apply to scRNAseq. GEFMAP leverages the natural graph structure of metabolic networks to learn both a biological objective for each cell and estimate a mass-balanced relative flux rate for each reaction in each cell using novel deep learning models.PMID:38105974 | PMC:PMC10723270 | DOI:10.1101/2023.12.05.570153

Metabolomics of Mouse Embryonic CSF Following Maternal Immune Activation

Mon, 18/12/2023 - 12:00
bioRxiv. 2023 Dec 8:2023.12.06.570507. doi: 10.1101/2023.12.06.570507. Preprint.ABSTRACTThe cerebrospinal fluid (CSF) provides a protective fluid cushion for the brain (Fame & Lehtinen, 2020; Lacey et al , 2023)and delivers neuroactive proteins, peptides, and small molecules that are critical for normal brain development (Saunders et al , 2023; Gelb & Lehtinen, 2023). In the case of the developing cerebral cortex, whose neural progenitor cells line the brain's ventricles and extend primary cilia into the CSF, age-appropriate cocktails of CSF growth factors help ensure that progenitors remain healthy, acquire the correct identity, and proliferate in a developmentally appropriate manner(Chau et al , 2018; Lehtinen et al , 2011; Kim et al , 2010). Conversely, the CSF can be used as a readout of different stages of brain development including metabolic state (Chau et al , 2018; Fame et al , 2019). Indeed, CSF is commonly sampled for biomarkers of infections and neurologic diseases.PMID:38105934 | PMC:PMC10723469 | DOI:10.1101/2023.12.06.570507

Study on mechanisms of comorbidity between hepatocellular steatosis and atherosclerosis based on metabolomics and network pharmacology

Mon, 18/12/2023 - 12:00
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2023 Dec 17:1-16. doi: 10.3724/zdxbyxb-2023-0315. Online ahead of print.ABSTRACTOBJECTIVES: To investigate the mechanism of comorbidity between non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (AS) based on metabolomics and network pharmacology.METHODS: Six ApoE-/- mice were fed with a high-fat diet for 16 weeks to construct a co-morbid model of NAFLD and AS (model group) and a normal diet was given to 6 wild-type C57BL/6J mice (control group). Serum samples were taken from both groups for a non-targeted metabolomics assay to identify the differential metabolites. The network pharmacology was applied to explore the possible mechanism of the effect of differential metabolites on AS and NAFLD. An in vitro co-morbid cell model was constructed using NCTC1469 cells and RAW264.7 macrophage. The cellular lipid accumulation, cell viability, morphology and function of mitochondria were detected with oil red O staining, CCK-8 assay, transmission electron microscopy and JC-1 staining, respectively.RESULTS: A total of 85 differential metabolites associated with comorbidity of NAFLD and AS were identified. The top 20 differential metabolites were subjected to network pharmacology analysis, which showed that the core targets of differential metabolites related to AS and NAFLD were STAT3, EGFR, MAPK14, PPARG, NFKB1, PTGS2, ESR1, PPARA, PTPN1, and SCD. The Kyoto Encyclopedia of Genes and Genomes showed a significant association with the PPAR signaling pathway, AGE-RAGE signaling pathway in diabetic complications, alcoholic liver disease, prolactin signaling pathway, insulin resistance, TNF signaling pathway, hepatitis B, the relax in signaling pathway and IL-17 signaling pathway was related to NAFLD. Cell experimental validation results showed that lipid metabolism-related genes PPARG, PPARA, PTPN1, and SCD were significantly changed in hepatocyte models, and steatotic hepatocytes affected the expression of macrophage inflammation-related genes STAT3, NFKB1, and PTGS2; steatotic hepatocytes promoted the formation of foam cells and exacerbated the accumulation of lipids in foam cells; the disrupted morphology, impaired function, and increased reactive oxygen species production were observed in steatotic hepatocyte mitochondria, while foam cell formation exacerbated the mitochondrial damage.CONCLUSIONS: The abnormal lipid metabolism and inflammatory response are the distinctive features of the co-morbid model of AS and NAFLD, which were interreacted with each other. Hepatocyte steatosis causes mitochondrial damage, which leads to mitochondrial dysfunction, increased reactive oxygen species and activation of the macrophage inflammatory response, resulting in the acceleration of AS development.PMID:38105677 | DOI:10.3724/zdxbyxb-2023-0315

Comparative metabolomic analysis reveals nutritional properties and pigmentation mechanism of tea-scented rosehips

Sun, 17/12/2023 - 12:00
J Sci Food Agric. 2023 Dec 17. doi: 10.1002/jsfa.13224. Online ahead of print.ABSTRACTBACKGROUND: The fruits of the genus Rosa, commonly known as rosehips, have attracted significant attention owing to their rich content of various bioactive compounds. However, their utility is generally secondary to the ornamental appeal of their flowers. The present study aimed to explore the quality differences among tea-scented rosehips found in Yunnan, China, including those of Rosa odorata var. odorata (RO), Rosa odorata var. gigantea (RG), and Rosa yangii (RY). Morphological characteristics, chemical composition, and antioxidant activity of their fruits were evaluated.RESULTS: The study revealed significant variability in composition and biological activities based on fruit color. RO exhibited the highest levels of polyphenols, flavonoids, anthocyanins, carotenoids, and vitamin C, with the strongest antioxidant activity (10.99 μmol Trolox·g-1 ), followed by RG (7.91 μmol Trolox·g-1 ) and RY (6.52 μmol Trolox·g-1 ). This supports RO's potential as a functional food source. Untargeted metabolomics identified and quantified 502 metabolites, with flavonoids (171) and phenolic acid (147) as the main metabolites. The differential metabolites among the fruits are primarily enriched for flavonoid biosynthesis and phenylpropanoid biosynthesis pathways. Insights into color formation supported the role of anthocyanins, flavones, and flavonols in fruit color variation.CONCLUSION: Tea-scented rosehips offer vibrant colors and high nutritional value with potent biological activities. RO stands out as a functional food source owing to its rich bioactive compounds. These findings lay the groundwork for utilizing rosehips in functional foods, health supplements, and food additives, emphasizing the practical and beneficial applications of Rosa spp. independent of their ornamental value. This article is protected by copyright. All rights reserved.PMID:38105397 | DOI:10.1002/jsfa.13224

Integrated network pharmacology and metabolomics reveal the mechanisms of Jasminum elongatum in anti-ulcerative colitis

Sun, 17/12/2023 - 12:00
Sci Rep. 2023 Dec 17;13(1):22449. doi: 10.1038/s41598-023-49792-w.ABSTRACTJasminum elongatum (JE), an ethnic Chinese medicine, is widely used in the Lingnan region of China, because of its analgesic and antidiarrheal action, as well as its anti-inflammatory effects in gastrointestinal diseases. However, whether JE could against ulcerative colitis (UC) remains unclear. This research aims to reveal JE in treating UC and clarify the underlying mechanism. We used the 2.5% dextran sulfate sodium (DSS)-induced UC mice (C57BL/6J) to evaluate the therapeutic effects of JE. Metabolomics of serum and network pharmacology were combined to draw target-metabolite pathways. Apart from that, the targets of associated pathways were confirmed, and the mechanism of action was made clear, using immunohistochemistry. The pharmacodynamic results, including disease activity index (DAI), histological evaluation, and inflammatory cytokines in colon tissues, demonstrated that JE significantly relieved the physiological and pathological symptoms of UC. Network pharmacology analysis indicated 25 core targets, such as TNF, IL-6, PTGS2 and RELA, and four key pathways, including the NF-κB signaling pathway and arachidonic acid metabolism pathway, which were the key connections between JE and UC. Metabolomics analysis identified 45 endogenous differential metabolites and 9 metabolic pathways by enrichment, with the arachidonic acid metabolism pathway being the main metabolism pathway, consistent with the prediction of network pharmacology. IκB, p65 and COX-2 were identified as key targets and this study demonstrated for the first time that JE reverses 2.5% DSS-induced UC in mice via the IκB/p65/COX-2/arachidonic acid pathway. This study reveals the complex mechanisms underlying the therapeutic effects of JE on UC and provides a new approach to identifying the underlying mechanisms of the pharmacological action of Chinese natural medicines such as JE.PMID:38105335 | DOI:10.1038/s41598-023-49792-w

Molecular insights and omics-based understanding of plant-microbe interactions under drought stress

Sun, 17/12/2023 - 12:00
World J Microbiol Biotechnol. 2023 Dec 18;40(2):42. doi: 10.1007/s11274-023-03837-4.ABSTRACTThe detrimental effects of adverse environmental conditions are always challenging and remain a major concern for plant development and production worldwide. Plants deal with such constraints by physiological, biochemical, and morphological adaptations as well as acquiring mutual support of beneficial microorganisms. As many stress-responsive traits of plants are influenced by microbial activities, plants have developed a sophisticated interaction with microbes to cope with adverse environmental conditions. The production of numerous bioactive metabolites by rhizospheric, endo-, or epiphytic microorganisms can directly or indirectly alter the root system architecture, foliage production, and defense responses. Although plant-microbe interactions have been shown to improve nutrient uptake and stress resilience in plants, the underlying mechanisms are not fully understood. "Multi-omics" application supported by genomics, transcriptomics, and metabolomics has been quite useful to investigate and understand the biochemical, physiological, and molecular aspects of plant-microbe interactions under drought stress conditions. The present review explores various microbe-mediated mechanisms for drought stress resilience in plants. In addition, plant adaptation to drought stress is discussed, and insights into the latest molecular techniques and approaches available to improve drought-stress resilience are provided.PMID:38105277 | DOI:10.1007/s11274-023-03837-4

Multi-integrated genomic data for Passiflora foetida provides insights into genome size evolution and floral development in Passiflora

Sun, 17/12/2023 - 12:00
Mol Hortic. 2023 Dec 18;3(1):27. doi: 10.1186/s43897-023-00076-x.ABSTRACTPassiflora is a plant genus known for its extremely distinctive and colorful flowers and a wide range of genome size variation. However, how genome characteristics are related to flower traits among Passiflora species remains poorly understood. Here, we assembled a chromosome-scale genome of P. foetida, which belongs to the same subgenus as the commercial passionfruit P. edulis. The genome of P. foetida is smaller (424.16 Mb) and contains fewer copies of long terminal repeat retrotransposons (LTR-RTs). The disparity in LTR-RTs is one of the main contributors to the differences in genome sizes between these two species and possibly in floral traits. Additionally, we observed variation in insertion times and copy numbers of LTR-RTs across different transposable element (TE) lineages. Then, by integrating transcriptomic data from 33 samples (eight floral organs and flower buds at three developmental stages) with phylogenomic and metabolomic data, we conducted an in-depth analysis of the expression, phylogeny, and copy number of MIKC-type MADS-box genes and identified essential biosynthetic genes responsible for flower color and scent from glandular bracts and other floral organs. Our study pinpoints LRT-RTs as an important player in genome size variation in Passiflora species and provides insights into future genetic improvement.PMID:38105261 | DOI:10.1186/s43897-023-00076-x

Construction of algal-bacterial consortia using green microalgae Chlorella vulgaris and As(III)-oxidizing bacteria: As tolerance and metabolomic profiling

Sun, 17/12/2023 - 12:00
J Environ Sci (China). 2024 May;139:258-266. doi: 10.1016/j.jes.2023.04.003. Epub 2023 Apr 14.ABSTRACTBioremediation became a promising technology to resolve arsenic (As) contamination in aquatic environment. Since monoculture such as microalgae or bacteria was sensitive to environmental disturbance and vulnerable to contamination, green microalgae Chlorella vulgaris and arsenite (As(III)) - oxidizing bacteria Pseudomonas sp. SMS11 were co-cultured to construct algal-bacterial consortia in the current study. The effects of algae-bacteria (A:B) ratio and exposure As(III) concentration on algal growth, As speciation and metabolomic profile were investigated. Algal growth arrested when treated with 100 mg/L As(III) without the co-cultured bacteria. By contrast, co-cultured with strain SMS11 significantly enhanced As tolerance in C. vulgaris especially with A:B ratio of 1:10. All the As(III) in culture media of the consortia were oxidized into As(V) on day 7. Methylation of As was observed on day 14. Over 1% and 0.5% of total As were converted into dimethylarsinic acid (DMA) after 21 days cultivation when the initial concentrations of As(III) were 1 and 10 mg/L, respectively. Metabolomic analysis was further performed to reveal the response of consortia metabolites to external As(III). The enriched metabolomic pathways were associated with carbohydrate, amino acid and energy metabolisms. Tricarboxylic acid cycle and glyoxylate and dicarboxylate metabolism were upregulated under As stress due to their biological functions on alleviating oxidative stress and protecting cells. Both carbohydrate and amino acid metabolisms provided precursors and potential substrates for energy production and cell protection under abiotic stress. Alterations of the pathways relevant to carbohydrate or amino acid metabolism were triggered by energy requirement.PMID:38105053 | DOI:10.1016/j.jes.2023.04.003

Postweaning intermittent sleep deprivation enhances defensive attack in adult female mice via the microbiota-gut-brain axis

Sun, 17/12/2023 - 12:00
Prog Neuropsychopharmacol Biol Psychiatry. 2023 Dec 15:110915. doi: 10.1016/j.pnpbp.2023.110915. Online ahead of print.ABSTRACTSleep is one of the most important physiological activities in life and promotes the growth and development of an individual. In modern society, sleep deprivation (SD), especially among adolescents, has become a common phenomenon. However, long-term SD severely affected adolescents' neurodevelopment leading to abnormal behavioral phenotypes. Clinical studies indicated that sleep problems caused increased aggressive behavior in adolescents. Aggressive behavior was subordinate to social behaviors, in which defensive attack was often the last line for survival. Meanwhile, increasing studies shown that gut microbiota regulated social behaviors by affecting specific brain regions via the gut-brain axis. However, whether postweaning intermittent SD is related to defensive attack in adulthood, and if so, whether it is mediated by the microbiota-gut-brain axis are still elusive. Combined with microbial sequencing and hippocampal metabolomics, the present study mainly investigated the long-term effects of postweaning intermittent SD on defensive attack in adult mice. Our study demonstrated that postweaning intermittent SD enhanced defensive attack and impaired long-term memory formation in adult female mice. Moreover, microbial sequencing and LC-MS analysis showed that postweaning intermittent SD altered the gut microbial composition and the hippocampal metabolic profile in female mice, respectively. Our attention has been drawn to the neuroactive ligand-receptor interaction pathway and related metabolites. In conclusion, our findings provide a new perspective on the relationship of early-life SD and defensive attack in adulthood, and also highlight the importance of sleep in early-life, especially in females.PMID:38104921 | DOI:10.1016/j.pnpbp.2023.110915

Effects of biochar-derived dissolved organic matter on the gut microbiomes and metabolomics in earthworm Eisenia fetida

Sun, 17/12/2023 - 12:00
Environ Res. 2023 Dec 15:117932. doi: 10.1016/j.envres.2023.117932. Online ahead of print.ABSTRACTThe ecological risks of biochar-derived dissolved organic matter (DOM) to soil invertebrates at different organismal levels remains limited. This study comprehensively explored the ecological risks of biochar-derived DOM on earthworm gut through assessments of enzyme activity response, histopathology, gut microbiomes, and metabolomics. Results demonstrated that DOM disturbed the digestive enzymes in earthworm, especially for 10% DOM300 groups. The integrated biomarker response v2 (IBRv2) indicated that the perturbation of earthworm digestive enzymes induced by DOM was both time-dependent and dose-dependent. Pathological observations revealed that 10% DOM300 damaged intestinal epithelium and digestive lumen of earthworms. The significant damage and injury to earthworms caused by DOM300 due to its higher concentrations of heavy metal ions and organic substrates (e.g., toluene, hexane, butanamide, and hexanamide) compared to DOM500 and DOM700. Analysis of 16S rRNA from the gut microbiota showed a significant decrease in genera (Verminephrobacter, Bacillus, and Microbacteriaceae) associated with inflammation, disease, and detoxification processes. Furthermore, 10% DOM300 caused the abnormality of metabolites, such as glutamate, fumaric acid, pyruvate, and citric acid, which were involved in energy metabolism, These findings contributed to improve our understanding of the toxic mechanism of biochar DOM from multiple perspectives.PMID:38104913 | DOI:10.1016/j.envres.2023.117932

Bioactives and metabolites of Tetrastigma hemsleyanum root extract alleviate DSS-induced ulcerative colitis by targeting the SYK protein in the B cell receptor signaling pathway

Sun, 17/12/2023 - 12:00
J Ethnopharmacol. 2023 Dec 15:117563. doi: 10.1016/j.jep.2023.117563. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum is an endemic Chinese herb with a wide range of pharmacological activities, including anti-inflammatory, antiviral, antioxidant, antitumor, and immunomodulatory activities. However, the effect and mechanisms of the anti-inflammatory activity of T. hemsleyanum root extract against dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) have not yet been fully investigated.AIM OF THE STUDY: This study aimed to explore the therapeutic effect and molecular mechanisms of T. hemsleyanum root extract in DSS-induced UC mice and knockdown cells.MATERIALS AND METHODS: T. hemsleyanum root extract was obtained and analyzed by high-performance liquid chromatography (HPLC). The therapeutic effects of T. hemsleyanum root extract on DSS-induced UC mice were evaluated by the disease activity index (DAI) score, colon length, serum inflammatory cytokines and oxidant/antioxidant levels, and histopathological features of the ileum and colon. Genome-wide gene expression profiles of ileal and colonic tissues were collected by transcriptomics, and signaling pathways were analyzed by the KEGG database. UC-related pathways were uploaded to the STRING database, then the protein-protein interactions (PPIs) were determined by Cytoscape, and the enriched genes were evaluated by real-time quantitative PCR (qPCR). The protein-ligand complexes were docked by AutoDock, and the genes were knocked down in Caco-2 cells by shRNA. The non-targeted metabolomic profiling of ileal contents was analyzed by ultra-high-performance liquid chromatography (UHPLC), and gut microflora were sequenced by an Illumina MiSeq System.RESULTS: Ten components that alleviated UC symptoms in mice by decreasing the DAI and serum inflammatory cytokines and oxidant levels, promoting intestinal development, and increasing serum antioxidant levels were identified in T. hemsleyanum root extract. T. hemsleyanum root extract activated the B cell receptor signaling pathway in the colon tissue of UC mice, in which two components, rutin and astragaline, bound to the spleen tyrosine kinase (SYK) protein but also restored gut microflora diversity and increased the proportion of probiotics. Furthermore, metabolites of T. hemsleyanum root extract were involved in vitamin metabolism, fatty acid metabolism, and ferroptosis.CONCLUSIONS: The rutin and astragaline components of T. hemsleyanum root extract, by binding to SYK protein, activated the B cell receptor signaling pathway and restored gut microflora diversity to alleviate UC symptoms in mice.PMID:38104876 | DOI:10.1016/j.jep.2023.117563

Metabolome implies increased fatty acid utilization and histone methylation in the follicles from hyperandrogenic PCOS women

Sun, 17/12/2023 - 12:00
J Nutr Biochem. 2023 Dec 15:109548. doi: 10.1016/j.jnutbio.2023.109548. Online ahead of print.ABSTRACTWell-balanced metabolism is essential for the high-quality of oocytes, and metabolic fluctuations of follicular microenvironment potentially encourage functional changes in follicle cells, ultimately impacting the developmental potential of oocytes. Here, the global metabolomic profiles of follicular fluid from PCOS women with ovarian hyperandrogenism and non-hyperandrogenism were depicted by untargeted metabolome and transcriptome. In parallel, functional methods were employed to evaluate the possible impact of dysregulated metabolites on oocyte and embryo development. Our findings demonstrated that PCOS women exhibited distinct metabolic features in follicles, such as the increase in fatty acid utilization and the downregulation in amino acid metabolism. And intrafollicular androgen levels were positively correlated with contents of multiple fatty acids, suggesting androgen as one of the contributing factors to the metabolic abnormalities in PCOS follicles. Moreover, we further demonstrated that elevated levels of α-linolenic acid and H3K27me3 could hinder oocyte maturation, fertilization, and early embryo development. Hopefully, our data serve as a broad resource on the metabolic abnormalities of PCOS follicles, and advances in the relevant knowledge will allow the identification of biomarkers that predict the progression of PCOS and its poor pregnancy outcomes.PMID:38104867 | DOI:10.1016/j.jnutbio.2023.109548

Effects and mechanisms of polystyrene micro- and nano-plastics on the spread of antibiotic resistance genes from soil to lettuce

Sun, 17/12/2023 - 12:00
Sci Total Environ. 2023 Dec 15:169293. doi: 10.1016/j.scitotenv.2023.169293. Online ahead of print.ABSTRACTEffects of microplastics (MPs) and nanoplastics (NPs) on the spread of antibiotic resistance genes (ARGs) in soil-plant systems are still unclear. To investigate the spread and mechanisms of ARGs from soil to lettuce, lettuce was exposed to soil spiked with two environmentally relevant concentrations of polystyrene MPs (100 μm) and NPs (100 nm). Results showed that microorganisms that carried ARGs in soil were increased after exposure to MPs/NPs, which led to an increase in ARGs in roots. NPs were absorbed by roots and can be transported to leaves. Analysis of transcriptomics, proteomics and metabolomics indicated that high concentration of NPs regulated the expression of related genes and proteins and improved the accumulation of flavonoids in the lettuce, therefore decreased the abundance of microorganisms that contained ARGs. Our work emphasizes the size and dose influences of MPs and NPs on the spread of ARGs from soil to plant.PMID:38104810 | DOI:10.1016/j.scitotenv.2023.169293

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