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

Transcriptome and Metabolome Analyses Reveal a Complex Stigma Microenvironment for Pollen Tube Growth in Tobacco

Wed, 27/11/2024 - 12:00
Int J Mol Sci. 2024 Nov 14;25(22):12255. doi: 10.3390/ijms252212255.ABSTRACTIn flowering plants, the success of fertilization depends on the rapid polar extension of a pollen tube, which delivers sperm cells to the female gametophyte for fertilization. Numerous studies have shown that the microenvironment in planta is more conducive to the growth and development of pollen tubes than that in vitro. However, how stigma factors coordinate to regulate pollen tube growth is still poorly understood. Here, we demonstrate that in tobacco, mature stigma extract, but not immature stigma extract, facilitates pollen tube growth. Comparative transcriptomic and qRT-PCR analyses showed that the differentially expressed genes during stigma maturation were mainly enriched in the metabolism pathway. Through metabolome analyses, about 500 metabolites were identified to be differently accumulated; the significantly increased metabolites in the mature stigmas mainly belonged to alkaloids, flavonoids, and terpenoids, while the downregulated differential metabolites were related to lipids, amino acids, and their derivatives. Among the different kinds of plant hormones, the cis-form contents of zeatin were significantly increased, and more importantly, cis-zeatin riboside promoted pollen tube growth in vitro. Thus, our results reveal an overall landscape of gene expression and a detailed nutritional microenvironment established for pollen tube growth during the process of stigma maturation, which provides valuable clues for optimizing in vitro pollen growth and investigating the pollen-stigma interaction.PMID:39596319 | DOI:10.3390/ijms252212255

Advantages of Metabolomics-Based Multivariate Machine Learning to Predict Disease Severity: Example of COVID

Wed, 27/11/2024 - 12:00
Int J Mol Sci. 2024 Nov 13;25(22):12199. doi: 10.3390/ijms252212199.ABSTRACTThe COVID-19 outbreak caused saturations of hospitals, highlighting the importance of early patient triage to optimize resource prioritization. Herein, our objective was to test if high definition metabolomics, combined with ML, can improve prognostication and triage performance over standard clinical parameters using COVID infection as an example. Using high resolution mass spectrometry, we obtained metabolomics profiles of patients and combined them with clinical parameters to design machine learning (ML) algorithms predicting severity (herein determined as the need for mechanical ventilation during patient care). A total of 64 PCR-positive COVID patients at the Poitiers CHU were recruited. Clinical and metabolomics investigations were conducted 8 days after the onset of symptoms. We show that standard clinical parameters could predict severity with good performance (AUC of the ROC curve: 0.85), using SpO2, first respiratory rate, Horowitz quotient and age as the most important variables. However, the performance of the prediction was substantially improved by the use of metabolomics (AUC = 0.92). Our small-scale study demonstrates that metabolomics can improve the performance of diagnosis and prognosis algorithms, and thus be a key player in the future discovery of new biological signals. This technique is easily deployable in the clinic, and combined with machine learning, it can help design the mathematical models needed to advance towards personalized medicine.PMID:39596265 | DOI:10.3390/ijms252212199

Non-ionic surfactant vesicles exert anti-inflammatory effects through inhibition of NFκB

Tue, 26/11/2024 - 12:00
J Inflamm (Lond). 2024 Nov 26;21(1):49. doi: 10.1186/s12950-024-00419-5.ABSTRACTInflammation can be an unwanted consequence or cause of debilitating diseases of infectious and non-infectious aetiologies. Current anti-inflammatory medications have several deficiencies including lack of specificity and undesirable side effects. Herein, the potential of non-ionic surfactant vesicles (NISV) comprised of monopalmityol glycerol, dicetyl phosphate and cholesterol) as an anti-inflammatory drug and their mode of action is investigated. NISV were able to inhibit LPS-induced IL-6 from BMD macrophages. The individual components of NISV, monopalmityol glycerol, dicetyl phosphate and cholesterol did not affect LPS induced IL-6 levels, proving that formulation of NISV is essential for their anti-inflammatory effects. Transcriptomic analyses showed NISV mediated down-regulation of transcripts for inflammatory mediators in LPS stimulated macrophages. Notably, NISV downregulate NF-κB transcripts in LPS stimulated macrophages. Measurement of inflammatory mediators by cytometric bead array validated a number of transcriptomic findings as NISV were found to inhibit LPS induced IL-6, IL-12, and multiple chemokines. Further investigation demonstrated that NISV inhibited Poly(I:C) or Pam3csk4 induced inflammatory mediators. This indicates that the effects of NISV are distal to both MyD88 and TRIF signalling. Overall, the data generated highlights the potential of NISV as an anti-inflammatory therapeutic.PMID:39593021 | DOI:10.1186/s12950-024-00419-5

Transcriptome and metabolome reveal the primary and secondary metabolism changes in Larix gmelinii seedlings under abiotic stress

Tue, 26/11/2024 - 12:00
BMC Plant Biol. 2024 Nov 27;24(1):1128. doi: 10.1186/s12870-024-05831-w.ABSTRACTBACKGROUND: Larix gmelinii is an excellent stress resistant coniferous tree species with a wide distribution and important economic and ecological value. However, at seedling stage, L. gmelinii is extremely susceptible to abiotic stresses, and systematic research on the adaptation mechanisms of L. gmelinii seedlings to abiotic stress is still lacking.RESULTS: Phenotypic observation and physiological index detection showed that L. gmelinii seedlings wilted with needles withered and yellowish at later stages of drought and salt stress; Under low temperature, the seedlings grew slowly and turned red at later stage. Under all 3 abiotic stresses, the chlorophyll content in seedlings significantly decreased, while the MDA content significantly increased; The activity of SOD and CAT showed a trend of increasing first and then decreasing. Transcriptome analysis revealed that DEGs were mainly involved in carbohydrate and amino acid metabolism, phenylpropanoid biosynthesis, and flavonoid synthesis metabolism. Metabolomic analysis found unique DAMs under 3 stress treatments. The combined analysis of transcriptome and metabolome showed that the changing patterns of DEGs and DAMs in primary and secondary metabolism were consistent: carbohydrate were significantly accumulated under low temperature stress; amino acids showed the most significant changes under salt stress. The variation pattern of secondary metabolism was similar under both drought and salt stress, while anthocyanin accumulation was the most obvious only under low temperature stress.CONCLUSION: Our study provides insightful information about the different mechanisms that L. gmelinii seedlings employ in response to drought, low temperature or salt stress.PMID:39592952 | DOI:10.1186/s12870-024-05831-w

Nitrate assimilation pathway is impacted in young tobacco plants overexpressing a constitutively active nitrate reductase or displaying a defective CLCNt2

Tue, 26/11/2024 - 12:00
BMC Plant Biol. 2024 Nov 27;24(1):1132. doi: 10.1186/s12870-024-05834-7.ABSTRACTBACKGROUND: We have previously shown that the expression of a constitutively active nitrate reductase variant and the suppression of CLCNt2 gene function (belonging to the chloride channel (CLC) gene family) in field-grown tobacco reduces tobacco-specific nitrosamines (TSNA) accumulation in cured leaves and cigarette smoke. In both cases, TSNA reductions resulted from a strong diminution of free nitrate in the leaf, as nitrate is a precursor of the TSNA-producing nitrosating agents formed during tobacco curing and smoking. These nitrosating agents modify tobacco alkaloids to produce TSNAs, the most problematic of which are NNN (N-nitrosonornicotine) and NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone). The expression of a deregulated nitrate reductase enzyme (DNR) that is no longer responsive to light regulation is believed to diminish free nitrate pools by immediately channeling incoming nitrate into the nitrate assimilation pathway. The reduction in nitrate observed when the two tobacco gene copies encoding the vacuolar nitrate transporter CLCNt2 were down-regulated by RNAi-mediated suppression or knocked out using the CRISPR-Cas technology was mechanistically distinct; likely attributable to the inability of the tobacco cell to efficiently sequester nitrate into the vacuole where this metabolite is protected from further assimilation. In this study, we used transcriptomic and metabolomic analyses to compare the nitrate assimilation response in tobacco plants either expressing DNR or lacking CLCNt2 function.RESULTS: When grown in a controlled environment, both DNR and CLCNt2-KO (CLCKO) plants exhibited (1) reduced nitrate content in the leaf; (2) increased N-assimilation into the amino acids Gln and Asn; and (3) a similar pattern of differential regulation of several genes controlling stress responses, including water stress, and cell wall metabolism in comparison to wild-type plants. Differences in gene regulation were also observed between DNR and CLCKO plants, including genes encoding nitrite reductase and asparagine synthetase.CONCLUSIONS: Our data suggest that even though both DNR and CLCKO plants display common characteristics with respect to nitrate assimilation, cellular responses, water stress, and cell wall remodeling, notable differences in gene regulatory patterns between the two low nitrate plants are also observed. These findings open new avenues in using plants fixing more nitrogen into amino acids for plant improvement or nutrition perspectives.PMID:39592946 | DOI:10.1186/s12870-024-05834-7

Author Correction: PNPO-PLP axis senses prolonged hypoxia in macrophages by regulating lysosomal activity

Tue, 26/11/2024 - 12:00
Nat Metab. 2024 Nov 26. doi: 10.1038/s42255-024-01183-9. Online ahead of print.NO ABSTRACTPMID:39592844 | DOI:10.1038/s42255-024-01183-9

Discriminating Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and comorbid conditions using metabolomics in UK Biobank

Tue, 26/11/2024 - 12:00
Commun Med (Lond). 2024 Nov 26;4(1):248. doi: 10.1038/s43856-024-00669-7.ABSTRACTBACKGROUND: Diagnosing complex illnesses like Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is complicated due to the diverse symptomology and presence of comorbid conditions. ME/CFS patients often present with multiple health issues, therefore, incorporating comorbidities into research can provide a more accurate understanding of the condition's symptomatology and severity, to better reflect real-life patient experiences.METHODS: We performed association studies and machine learning on 1194 ME/CFS individuals with blood plasma nuclear magnetic resonance (NMR) metabolomics profiles, and seven exclusive comorbid cohorts: hypertension (n = 13,559), depression (n = 2522), asthma (n = 6406), irritable bowel syndrome (n = 859), hay fever (n = 3025), hypothyroidism (n = 1226), migraine (n = 1551) and a non-diseased control group (n = 53,009).RESULTS: We present a lipoprotein perspective on ME/CFS pathophysiology, highlighting gender-specific differences and identifying overlapping associations with comorbid conditions, specifically surface lipids, and ketone bodies from 168 significant individual biomarker associations. Additionally, we searched for, trained, and optimised a machine learning algorithm, resulting in a predictive model using 19 baseline characteristics and nine NMR biomarkers which could identify ME/CFS with an AUC of 0.83 and recall of 0.70. A multi-variable score was subsequently derived from the same 28 features, which exhibited ~2.5 times greater association than the top individual biomarker.CONCLUSIONS: This study provides an end-to-end analytical workflow that explores the potential clinical utility that association scores may have for ME/CFS and other difficult to diagnose conditions.PMID:39592839 | DOI:10.1038/s43856-024-00669-7

Metabolomics analysis reveals resembling metabolites between humanized gammadelta TCR mice and human plasma

Tue, 26/11/2024 - 12:00
Sci Rep. 2024 Nov 26;14(1):29321. doi: 10.1038/s41598-024-81003-y.ABSTRACTGamma delta (γδ) T cells, which reside in mucosal and epithelial tissues, are integral to immune responses and are involved in various cancers, autoimmune, and infectious diseases. To study human γδ T cells to a translational level, we developed γδ humanized TCR-T1 (HuTCR-T1) mice using our TruHumanization platform. We compared the metabolomic profiles from plasma samples of wild-type (WT), γδ HuTCR-T1 mice, and humans using UHPLC-MS/MS. Untargeted metabolomics and lipidomics were used to screen all detectable metabolites. Principal component analysis revealed that the metabolomic profiles of γδ HuTCR-T1 mice closely resemble those of humans, with a clear segregation of metabolites between γδ HuTCR-T1 and WT mice. Most humanized γδ metabolites were classified as lipids, followed by organic compounds and amino acids. Pathway analysis identified significant alterations in the metabolism of tryptophan, tyrosine, sphingolipids, and glycerophospholipids, shifting these pathways towards a more human-like profile. Immunophenotyping showed that γδ HuTCR-T1 mice maintained normal proportions of both lymphoid and myeloid immune cell populations, closely resembling WT mice, with only a few exceptions. These findings demonstrate that the γδ HuTCR-T1 mouse model exhibits a metabolomic profile that is remarkably similar to that of humans, highlighting its potential as a relevant model for investigating the role of metabolites in disease development and progression. This model also offers an opportunity to discover therapeutic human TCRs.PMID:39592837 | DOI:10.1038/s41598-024-81003-y

Metabolomics and (13)C labelled glucose tracing to identify carbon incorporation into aberrant cell membrane glycans in cancer

Tue, 26/11/2024 - 12:00
Commun Biol. 2024 Nov 26;7(1):1576. doi: 10.1038/s42003-024-07277-0.ABSTRACTCell membrane glycans contribute to immune recognition, signaling, and cellular adhesion and migration, and altered membrane glycosylation is a feature of cancer cells that contributes to cancer progression. The uptake and metabolism of glucose and other nutrients essential for glycan synthesis could underlie altered membrane glycosylation, but the relationship between shifts in nutrient metabolism and the effects on glycans have not been directly examined. We developed a method that combines stable isotope tracing with metabolomics to enable direct observations of glucose allocation to nucleotide sugars and cell-membrane glycans. We compared the glucose allocation to membrane glycans of two pancreatic cancer cell lines that are genetically identical but have differing energy requirements. The 8988-S cells had higher glucose allocation to membrane glycans and intracellular pathways relating to glycan synthesis, but the 8988-T cells had higher glucose uptake and commitment of glucose to non-glycosylation pathways. The cell lines differed in the requirements of glucose for energy production, resulting in differences in glucose bioavailability for glycan synthesis. The workflow demonstrated here enables studies on the effects of metabolic shifts on the commitment of nutrients to cell-membrane glycans. The results suggest that cell-membrane glycans are remodeled through shifts in glucose commitment to non-glycosylation pathways.PMID:39592729 | DOI:10.1038/s42003-024-07277-0

Increased rumen Prevotella enhances BCAA synthesis, leading to synergistically increased skeletal muscle in myostatin-knockout cattle

Tue, 26/11/2024 - 12:00
Commun Biol. 2024 Nov 26;7(1):1575. doi: 10.1038/s42003-024-07252-9.ABSTRACTMyostatin (MSTN) is a negative regulator of muscle growth, and its relationship with the gut microbiota is not well understood. In this study, we observed increase muscle area and branched-chain amino acids (BCAAs), an energy source of muscle, in myostatin knockout (MSTN-KO) cattle. To explore the link between increased BCAAs and rumen microbiota, we performed metagenomic sequencing, metabolome analysis of rumen fluid, and muscle transcriptomics. MSTN-KO cattle showed a significant increase in the phylum Bacteroidota (formerly Bacteroidetes), particularly the genus Prevotella (P = 3.12e-04). Within this genus, Prevotella_sp._CAG:732, Prevotella_sp._MSX73, and Prevotella_sp._MA2016 showed significant upregulation of genes related to BCAA synthesis. Functional enrichment analysis indicated enrichment of BCAA synthesis-related pathways in both rumen metagenomes and metabolomes. Additionally, muscle transcriptomics indicated enrichment in muscle fiber and amino acid metabolism, with upregulation of solute carrier family genes, enhancing BCAA transport. These findings suggest that elevated rumen Prevotella in MSTN-KO cattle, combined with MSTN deletion, synergistically improves muscle growth through enhanced BCAA synthesis and transport.PMID:39592704 | DOI:10.1038/s42003-024-07252-9

Comparative lipidome and transcriptome provide novel insights into zero-valent iron nanoparticle-treated Fremyella diplosiphon

Tue, 26/11/2024 - 12:00
Sci Rep. 2024 Nov 26;14(1):29380. doi: 10.1038/s41598-024-79780-7.ABSTRACTUnderstanding the intricate interplay between nanoparticle-mediated cyanobacterial interactions is pivotal in elucidating their impact on the transcriptome and lipidome. In the present study, total fatty acid methyl esters (FAMEs) in the wild-type (B481-WT) and transformant (B481-SD) Fremyella diplosiphon strains treated with nanoscale zero-valent iron nanoparticles (nZVIs) were characterized, and transcriptome changes analyzed. Comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry revealed a 20-25% higher percentage of FAMEs in nZVI-treated F. diplosiphon strain B481-SD compared to B481-WT. Accumulation of alkanes was significantly higher (> 1.4 times) in both strains treated with 25.6 mg L-1 nZVIs compared to the untreated control. In addition, we observed significantly higher levels of monounsaturated FAMEs (11%) in B481-WT in 3.2 (11.34%) and 25.6 mg L-1 (11.22%) nZVI-treated cells when compared to the untreated control (7%). Analysis of the F. diplosiphon transcriptome treated with 3.2 mg L-1 revealed a total of 1811 and 1651 genes that were differentially expressed in B481-SD and B481-WT respectively. While the expression of iron uptake and ion channel genes was downregulated, genes coding for photosynthesis, pigment, and antioxidant enzymes were significantly (p < 0.05) upregulated in B481-SD treated with 3.2 mg L-1 nZVIs compared to the untreated control. This study on essential FAMEs and regulation of genes in nZVI-treated F. diplosiphon strains provides a molecular framework for optimization of metabolic pathways in this model species.PMID:39592694 | DOI:10.1038/s41598-024-79780-7

Mitochondrial DNA abundance and circulating metabolomic profiling: Multivariable-adjusted and Mendelian randomization analyses in UK Biobank

Tue, 26/11/2024 - 12:00
Mitochondrion. 2024 Nov 24:101991. doi: 10.1016/j.mito.2024.101991. Online ahead of print.ABSTRACTBACKGROUND: Low leukocyte mitochondrial DNA (mtDNA) abundance has been associated with a higher risk of atherosclerotic cardiovascular disease, but through unclear mechanisms. We aimed to investigate whether low mtDNA abundance is associated with worse metabolomic profiling, as being potential intermediate phenotypes, using cross-sectional and genetic studies.METHODS: Among 61,186 unrelated European participants from UK Biobank, we performed multivariable-adjusted linear regression analyses to examine the associations between mtDNA abundance and 168 NMR-based circulating metabolomic measures and nine metabolomic principal components (PCs) that collectively covered 91.5% of the total variation of individual metabolomic measures. Subsequently, we conducted Mendelian randomization (MR) to approximate the causal effects of mtDNA abundance on the individual metabolomic measures and their metabolomic PCs.RESULTS: After correction for multiple testing, low mtDNA abundance was associated with 130 metabolomic measures, predominantly lower concentrations of some amino acids and higher concentrations of lipids, lipoproteins and fatty acids; moreover, mtDNA abundance was associated with seven out of the nine metabolomic PCs. Using MR, genetically-predicted low mtDNA abundance was associated with lower lactate (standardized beta and 95% confidence interval: -0.17; -0.26, -0.08), and higher acetate (0.15; 0.07,0.23), and unsaturation degree (0.14; 0.08,0.20). Similarly, genetically-predicted low mtDNA abundance was associated with lower metabolomic PC2 (related to lower concentrations of lipids and fatty acids), and higher metabolomic PC9 (related to lower concentrations of glycolysis-related metabolites).CONCLUSION: Low mtDNA abundance is associated with metabolomic perturbations, particularly reflecting a pro-atherogenic metabolomic profile, which potentially could link low mtDNA abundance to higher atherosclerosis risk.PMID:39592086 | DOI:10.1016/j.mito.2024.101991

Soufeng sanjie formula alleviates osteoarthritis by inhibiting macrophage M1 polarization and modulating intestinal metabolites

Tue, 26/11/2024 - 12:00
J Ethnopharmacol. 2024 Nov 24:119147. doi: 10.1016/j.jep.2024.119147. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Osteoarthritis (OA) is defined as "bone bi" disease based on clinical symptoms in Chinese medicine. Soufeng sanjie formula (SF) is a traditional formula for treating "bone bi" disease, which consists of Scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch) (0.5 g), Scorpions (dried body of Buthus martensii Karsch) (0.5 g), Astragali radix (dried root of Astragalus membranaceus (Fisch.) Bge) (20 g) and Black soybean seed coats (seed coats of Glycine max (L.) Merr) (30 g), and it can be used to treat rheumatoid arthritis. Nonetheless, the potential of SF to postpone the advancement of OA and its underlying mechanisms remain unexplored.AIM OF THE STUDY: This study investigated whether SF could alleviate OA and the underlying mechanism.MATERIALS AND METHODS: Anterior cruciate ligament transection (ACLT) was performed to establish an OA mice model. Mechanical pain and cold pain were assessed to evaluate changes in pain sensitivity in OA mice. Micro-CT was used to observe the microstructure and quantify the bone morphological parameters of knee joints. Safranin O-fast green staining was used to evaluate cartilage damage, and Osteoarthritis Research Society International (OARSI) scores were calculated. Immunohistochemistry was used to assess the expression of inflammatory factors in the synovium of OA mice following SF administration. Immunofluorescence analyzed the fraction of CD80 and iNOS positive regions in the synovium of knee joints. The effect of SF on macrophage M1 polarization was investigated using flow cytometry, western blot and quantitative PCR (qPCR) in vitro. Untargeted metabolomics was used to identify the differential metabolites associated with OA.RESULTS: SF-treatment markedly reduced the cartilage damage, lowered the OARSI score and downregulated the pain sensitivity in the OA mice. Secondly, SF decreased the expression of IL-6, IL-1β, and TNF-α in the OA synovium. SF also reduced the percentage of CD80 and iNOS in the synovium of the knee joint after ACLT surgery by using immunofluorescence. Thirdly, SF inhibited the protein expression of iNOS and COX-2, decreased the percentage of CD80, and reduced the mRNA levels of IL-6, IL-1β, and TNF-α in BMDM cells. Furthermore, SF inhibited the macrophage M1 polarization-related AKT/NF-κB signaling pathway. Finally, untargeted metabolomics showed that SF changed the metabolic profile of the intestinal contents in OA mice, causing elevated levels of the pro-inflammatory metabolite 18-hydroxyoleic acid, which was effectively reduced by SF.CONCLUSION: Our results suggested that SF reduced pain symptoms and joint inflammation in mice with OA. Furthermore, SF inhibited synovial macrophage M1 polarization and modified the levels of the pro-inflammatory intestinal metabolite 18-hydroxyoleic acid in OA mice. Therefore, SF may be act as a potential Chinese medicine for the treatment of OA.PMID:39592076 | DOI:10.1016/j.jep.2024.119147

ACSL4 and polyunsaturated lipids support metastatic extravasation and colonization

Tue, 26/11/2024 - 12:00
Cell. 2024 Nov 19:S0092-8674(24)01270-4. doi: 10.1016/j.cell.2024.10.047. Online ahead of print.ABSTRACTMetastatic dissemination to distant organs demands that cancer cells possess high morphological and metabolic adaptability. However, contributions of the cellular lipidome to metastasis remain elusive. Here, we uncover a correlation between metastasis potential and ferroptosis susceptibility in multiple cancers. Metastases-derived cancer cells exhibited higher ferroptosis sensitivity and polyunsaturated fatty acyl (PUFA)-lipid contents than primary-tumor-derived cells from ovarian cancer patients. Metabolism-focused CRISPR screens in a mouse model for ovarian cancer distant metastasis established via two rounds of in vivo selection revealed the PUFA-lipid biosynthesis enzyme acyl-coenzyme A (CoA) synthetase long-chain family member 4 (ACSL4) as a pro-hematogenous metastasis factor. ACSL4 promotes metastatic extravasation by enhancing membrane fluidity and cellular invasiveness. While promoting metastasis, the high PUFA-lipid state creates dependencies on abhydrolase-domain-containing 6, acylglycerol lipase (ABHD6), enoyl-CoA delta isomerase 1 (ECI1), and enoyl-CoA hydratase 1 (ECH1)-rate-limiting enzymes preparing unsaturated fatty acids (UFAs) for β-oxidation. ACSL4/ECH1 co-inhibition achieved potent suppression of metastasis. Our work establishes the dual functions of PUFA-lipids in tumor progression and metastasis that may be exploitable for therapeutic development.PMID:39591965 | DOI:10.1016/j.cell.2024.10.047

Melatonin reprograms soil microbial community, creates friendly soil environments, and promotes peanut growth

Tue, 26/11/2024 - 12:00
Plant Physiol Biochem. 2024 Nov 22;218:109307. doi: 10.1016/j.plaphy.2024.109307. Online ahead of print.ABSTRACTMelatonin helps to regulate various physiological processes in plants, including growth, seed germination, and stress responses. However, the mechanism of how melatonin treatments affect soil microbe diversity and ecology, and plant growth needs to be better understood. Here, we report that melatonin coordinates interactions between soil microorganisms and root exudates to create a friendly soil environment for peanut growth under a controlled environment. Interestingly, the results showed that melatonin was capable of regulating the structure of the soil microbial community, improving its relative abundance of beneficial microorganisms (such as Sphingomonas, Trichoderma, and Penicillium) in the soil. Furthermore, melatonin could also change the composition of soil metabolites and nutrients. These altered soil profiles reflected a healthy environment for peanuts created by melatonin. Furthermore, the favorable growing environment increased photosynthetic performance, biomass, and peanut yield. Collectively, our findings will help us better understand the role of melatonin as a bioregulator in maintaining a healthy plant growth environment. SYNOPSIS: Melatonin treatments improved soil microbe biodiversity and enhanced plant growth and development and sustainable agricultural development.PMID:39591892 | DOI:10.1016/j.plaphy.2024.109307

Biochemical mechanism underlying the synthesis of PbS nanoparticle and its in-situ photo effect on Shinella zoogloeoides PQ7

Tue, 26/11/2024 - 12:00
J Hazard Mater. 2024 Nov 24;482:136652. doi: 10.1016/j.jhazmat.2024.136652. Online ahead of print.ABSTRACTMetal sulfide nanoparticles (NPs) with semiconductor potentials are valuable bioremediation end-products that attract great research interests. However, biochemical mechanisms underlying their biosynthesis and photo-effects remain elusive. In this study, we found that biofilm lifestyle remarkably improved lead resistance and PbS-NP biosynthesis in Shinella zoogloeoides PQ7. Surprisingly, biosynthesis of PbS-NP required more than cysteine and H2S production. Transcriptomic and metabolomic analysis indicated that PQ7 responded to lead stress by changing metabolic activities in ABC transporters, oxidative phosphorylation, EPS production, quorum sensing, protein de novo synthesis, flagella assembly and antioxidative reactions, etc. The elevated EPS production and quorum sensing gene expression echoed the favorable roles of biofilm formation in lead resistance. Biosynthesis of PbS-NP required proper oxygen supply, and was impeded by adding kanamycin or using yeast extract as the sole nutrient supply. Investigations on NAD/NADH, ATP, ROS and GSH productions indicated that biosynthesis of PbS-NP was corelated with cellular respiration, energy metabolism, and redox status. Finally, we proved that PbS-NP had the dose-dependent in-situ photo effect on PQ7's growth and ROS production. This is the first report that pinpoints the role of cellular respiration in PbS-NP biosynthesis, which is essential for further mechanism study and the development of bioremediation techniques.PMID:39591788 | DOI:10.1016/j.jhazmat.2024.136652

Microbial regulation of interspecific interaction and metabolism in anammox process to achieve coadaptation to artificial sweeteners

Tue, 26/11/2024 - 12:00
J Hazard Mater. 2024 Nov 24;482:136654. doi: 10.1016/j.jhazmat.2024.136654. Online ahead of print.ABSTRACTArtificial sweeteners (ASs) were frequently detectable in wastewater, which pose high risks to human health and ecological security. The feasibility of anaerobic ammonium oxidation (anammox) process for treatment of ASs-containing wastewater was evaluated in this study. The 86-d continuous flow experiment results showed that 0-30 μg L-1 cyclamate and acesulfame did not significantly affect the nitrogen removal efficiency (NRE) of anammox processes, which were 94.5 ± 3.0 % and 96.6 ± 2.5 %, respectively. Simultaneously, specific anammox activity (SAA) was inhibited by 15 μg L-1 ASs. Fortunately, anammox consortia adapted to the ASs stress by secreting extracellular polymeric substance (EPS). The relative abundances of Candidatus Kuenenia slightly decreased by 0.2 % and 2.3 % under stress of two ASs, and the microbial diversity increased. In addition, the anammox consortia regulated metabolites expression by cell energy allocation. The dominant metabolic pathways were amino acid metabolism, lipid metabolism and nucleotide metabolism. Particularly, the abundances of 5-hydroxylysinonorleucine and L-hypoglycin A significantly increased with ASs concentrations, which were crucial for bacterial proliferation. The co-metabolism between different bacteria might contribute to the biodegradation of ASs. This work demonstrates the feasibility of anammox process to treat the ASs-containing wastewater and reveals the regulation and adaptation mechanism of anammox microbiota, which further drives the implementation and development of anammox process.PMID:39591786 | DOI:10.1016/j.jhazmat.2024.136654

Development of a non-targeted metabolomics-based screening method for elucidating the metabolic characteristics and potential applications of Lacticaseibacillus paracasei

Tue, 26/11/2024 - 12:00
Food Chem. 2024 Nov 15;466:141943. doi: 10.1016/j.foodchem.2024.141943. Online ahead of print.ABSTRACTThe increasing demand for healthy foods has led to widespread interest in lactic acid bacteria due to their potential health benefits. We propose the hypothesis that Lacticaseibacillus paracasei (L. paracasei) can produce beneficial metabolites under specific conditions, which offers potential applications in functional foods. In this study, we analyzed the fermentation supernatants and brown fermented milk metabolites of L. paracasei to identify those with possible applications in functional foods, which have great potential. We found that L. paracasei IMAU32642 produced unique metabolites, including docosahexaenoic acid (DHA), leucyl phenylalanine, and oleic acid in its fermentation supernatant. Meanwhile, L. paracasei IMAU60048 exhibited unique application prospects in brown fermented milk, with higher yields of arachidonic acid and caprylic acid compared to other strains. This study offers a new and effective method for screening L. paracasei. The study can promote the development of functional foods and enhance their health value.PMID:39591773 | DOI:10.1016/j.foodchem.2024.141943

Cannabidiol regulates L-carnitine and butyric acid metabolism by modulating the gut microbiota to ameliorate collagen-induced arthritis

Tue, 26/11/2024 - 12:00
Phytomedicine. 2024 Nov 19;136:156270. doi: 10.1016/j.phymed.2024.156270. Online ahead of print.ABSTRACTBACKGROUND: Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, affecting multiple systems in the body. Cannabidiol (CBD) is one of the most medically valuable active ingredients in cannabis. At present, CBD has been shown to alleviate the progression of RA; however, owing to its multiple targets, the mechanism of CBD is not clear.METHODS: On the basis of the gut microbiota, we explored the mechanism by which CBD inhibits RA progression. Metagenomic and nontargeted metabolomic analyses were used to determine the changes in the intestinal ecology and plasma metabolites of collagen-induced arthritis (CIA) rats after CBD treatment.RESULTS: CBD reversed gut dysbiosis in CIA rats, notably altering the abundances of Allobaculum_unclassified, Allobaculum_fili, and Prevotella_unclassified. In addition, metabolomic analysis confirmed that CBD increased the contents of butyric acid and L-carnitine. Allobaculum could produce butyric acid and Prevotella could accelerate the metabolism of L-carnitine. In addition, in vitro experiments demonstrated that L-carnitine participated in the regulation of neutrophils, macrophages and RA-fibroblast-like synoviocytes (RA-FLSs), which was consistent with the synovial changes in CIA rats caused by CBD.CONCLUSION: In summary, CBD increased the plasma contents of butyric acid and L-carnitine by altering the abundances of gut microbiota, thereby inhibiting inflammation in neutrophils, macrophages and RA-FLSs. Our study is the first to explain the mechanism by which CBD alleviates progression in CIA rats from the perspective of gut microbes and metabolites, providing new views into CBD mechanisms, which warrants clinical attention.PMID:39591767 | DOI:10.1016/j.phymed.2024.156270

Effects of leachate from disposable plastic takeout containers on the cardiovascular system after thermal contact

Tue, 26/11/2024 - 12:00
Ecotoxicol Environ Saf. 2024 Nov 25;288:117383. doi: 10.1016/j.ecoenv.2024.117383. Online ahead of print.ABSTRACTThe study investigated the cardiovascular effects of daily exposure to plastic products by simulating the oral heat exposure mode of disposable plastic takeout containers (DPTC) commonly used in society. Questionnaires were used to randomly choose 3179 people in order to examine any possible correlation between the frequency of plastic exposure and the risk of cardiovascular diseases (CVD). Additionally, Sprague-Dawley(SD) rats consumed leachate from DPTC exposed to boiling water for 1 minute,5 minutes and 15 minutes respectively, over three months. After intervention, fecal samples were taken for microbiota and metabolomics analysis, and rat cardiac tissue was studied by staining and electron microscopy. Serum parameters were tested to analyze cardiovascular system changes. The population-based plastic exposure questionnaire data revealed that high-frequency exposure to plastics is significantly associated with an increased risk of congestive heart failure, with an odds ratio of 1.13 (95 % CI: 1.03-1.24). Rat fecal analysis revealed that β diversity and composition of gut microbiota in experimental groups were changed. Inflammatory cell infiltration, mitochondrial swelling, and serum indicators of oxidative stress and inflammation were significantly elevated in the myocardium, without temporal differences observed. The study shows plastic exposure as a significant CVD risk factor regardless of duration. It leads to changes in myocardial tissue, gut microbiota, and metabolites, all closely tied to CVD.PMID:39591733 | DOI:10.1016/j.ecoenv.2024.117383

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