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

Novel DART-MS approach for rapid and environmentally friendly determination of the geographical origin of hazelnuts (Corylus avellana L.)

Sun, 01/12/2024 - 12:00
Food Chem. 2024 Nov 26;467:142265. doi: 10.1016/j.foodchem.2024.142265. Online ahead of print.ABSTRACTDirect analysis in real time mass spectrometry (DART-MS) is a novel method for the authentication of food and feed that represents a serious alternative to established methods. This study aims to analyze hazelnuts from different origins and identify potential marker metabolites using a high-resolution DART-MS platform and a non-targeted metabolomics approach. To investigate the suitability of DART-MS for authenticating the origin of foods with a high fat content, 172 hazelnut samples from 5 countries were analyzed. Data evaluation using principal component analysis (PCA) and Random Forest-based classification led to an accuracy of 93.2 %, demonstrating the high valence of the DART-MS approach for verifying the origin of hazelnuts. In addition, 16 marker metabolites were identified and revealed the importance of di- and triacylglycerols for the authentication of hazelnuts. These results demonstrate the high suitability of DART-MS based analysis as a rapid, cost-effective, and environmentally friendly approach for food authentication.PMID:39616764 | DOI:10.1016/j.foodchem.2024.142265

Impacts of hexafluoropropylene oxide tetrameric acid (HFPO-TeA) on neurodevelopment and GABAergic signaling in zebrafish larvae

Sun, 01/12/2024 - 12:00
Ecotoxicol Environ Saf. 2024 Nov 30;289:117424. doi: 10.1016/j.ecoenv.2024.117424. Online ahead of print.ABSTRACTHexafluoropropylene oxide oligomer acids (HFPOs), an emerging environmental pollutant, are increasingly utilized in the manufacture of fluorinated synthetic materials as a substitute for traditional perfluorooctanoic acid (PFOA), resulting in a corresponding rise in detection rates in aquatic environments, which may present inherent safety hazards to ecosystems and public health. However, few data are available on the issue of their toxicity and mechanism. This study aimed to investigate the potential toxic effects of hexafluoroepoxypropane tetrameric acid (HFPO-TeA), a typical HFPO, on the early developmental stages of zebrafish larvae. It revealed that HFPO-TeA exposure resulted in significant detrimental effects, including adverse impacts on general morphological characteristics, such as eye area, heart rate, and swimming bladder, in zebrafish embryos and larvae. Targeted metabolomics and transcriptomics inquiries clarified that HFPO-TeA exposure reduced the levels of the neurotransmitter gamma-aminobutyric acid (GABA) and downregulated the expression of genes related to the GABA pathway. Simultaneously, transgenic zebrafish exhibited that exposure to HFPO-TeA impedes the growth of GABAergic neurons. Moreover, the molecular docking analysis indicated that GABAA receptors might be the potential targets of HFPO-TeA. Taken together, the current data highlights that the HFPO-TeA might not be safe alternatives to PFOA. This study presented a model for HFPO-TeA-induced neurotoxicity in developing zebrafish that can aid in ecological risk assessments.PMID:39616666 | DOI:10.1016/j.ecoenv.2024.117424

A multi-levels analysis to evaluate the toxicity of microplastics on aquatic insects: A case study with damselfly larvae (Ischnura elegans)

Sun, 01/12/2024 - 12:00
Ecotoxicol Environ Saf. 2024 Nov 30;289:117447. doi: 10.1016/j.ecoenv.2024.117447. Online ahead of print.ABSTRACTMicroplastic (MP) pollution prevalent in freshwater environments and jeopardizes the organisms living there. Dozens of studies have been conducted to investigate the harmful effects of microplastics on organisms. However, the most diverse and sensitive aquatic insects are often overlooked, also there is a lack of a comprehensive research exploring the toxicity of microplastics. Here, taking the damselfly larvae (Ischnura elegans) as the subject, we investigated the effects of different concentration levels of polystyrene microplastics (PS MPs) on their physiological characters, behavioristics, metabolomics and transcriptomics, as well as gut microbiome. The results showed that the PS MPs had no significant effects on the body weight and survival rate, but led to behavioral inhibition. Furthermore, expression levels of some metabolites altered, such as nicotinic acid, fumaric acid, and stearic acid. Meanwhile, the pathways related to oxidative phosphorylation and carbon metabolism were upregulated at the transcriptomic level. Moreover, there was a modification of the gut microbial community, with an increase in species richness but a shift towards potentially harmful bacteria. Our findings suggested that exposure to PS MPs affected the overall health of damselfly larvae. Therefore, effective management of MPs to minimize their environmental input is crucial in reducing health risks to aquatic organisms.PMID:39616662 | DOI:10.1016/j.ecoenv.2024.117447

Beyond Asexual: Genomics-Driven Progress in Unveiling Sexual Reproduction in Cereal Rust Fungi

Sun, 01/12/2024 - 12:00
Mol Plant Microbe Interact. 2024 Dec 1. doi: 10.1094/MPMI-10-24-0122-FI. Online ahead of print.ABSTRACTRecent advances in genomics technologies have revolutionized our understanding of cereal rust fungi, providing unprecedented insights into the complexities of their sexual life cycle. Genomic approaches, including long-read sequencing, genome assembly, and haplotype phasing technologies, have revealed critical insights into mating systems, genetic diversity, virulence evolution, and host adaptation. Population genomics studies have uncovered diverse reproductive strategies across different cereal rust species and geographic regions, highlighting the interplay between sexual recombination and asexual reproduction. Transcriptomics have begun to unravel the gene expression networks driving sexual reproduction, while complementary omics approaches such as proteomics, and metabolomics offer potential insights into the underlying molecular processes. Despite this progress, many aspects of rust sexual reproduction remain elusive. Integrating multiple omics approaches with advanced cell biology techniques can help address these knowledge gaps, particularly in understanding sexual reproduction and its role in pathogen evolution. This comprehensive approach will be crucial for developing more targeted and resilient crop protection strategies, ultimately contributing to global food security.PMID:39616556 | DOI:10.1094/MPMI-10-24-0122-FI

Gut Microbiota and Metabolite Profiles Associated With Functional Constipation Severity

Sun, 01/12/2024 - 12:00
Microbiol Immunol. 2024 Dec 1. doi: 10.1111/1348-0421.13187. Online ahead of print.ABSTRACTFunctional constipation (FC) is a common digestive disorder that affects patients' quality of life and is closely associated with intestinal tumors. This study used a cross-sectional design to assess the changes of intestinal flora and metabolites in different severities of FC patients through 16S rRNA sequencing and metabolomics analysis. Results showed that patients with severe FC had significantly higher clinical and anxiety scores compared to those in the mild and moderate groups. The species richness of intestinal microorganisms in the severe FC group was also significantly higher, and obvious differences in the flora composition existed. Specifically, the Bacteroidota was more abundant in the severe FC group, which was a characteristic feature distinguishing severe FC. Metabolomic analyses also revealed metabolite differences among patients with mild-to-moderate and severe FC, with the severe FC group showing increased enrichment in L-isoleucine biosynthesis and glycolysis metabolic pathways. The short-chain fatty acid-targeted metabolome suggested that a decrease in butyric acid might be related to worsening constipation. This study suggests that specific flora and metabolic pathways could serve as potential diagnostic and therapeutic targets, thereby contributing to the development of new diagnostic and therapeutic approaches to improve the quality of life and therapeutic outcomes for FC patients.PMID:39616526 | DOI:10.1111/1348-0421.13187

ASGR1 deficiency improves atherosclerosis but alters liver metabolism in ApoE<sup>-/-</sup> mice

Sat, 30/11/2024 - 12:00
Cardiovasc Diabetol. 2024 Nov 30;23(1):428. doi: 10.1186/s12933-024-02507-5.ABSTRACTThe asialoglycoprotein receptor 1 (ASGR1), a multivalent carbohydrate-binding receptor that primarily is responsible for recognizing and eliminating circulating glycoproteins with exposed galactose (Gal) or N-acetylgalactosamine (GalNAc) as terminal glycan residues, has been implicated in modulating the lipid metabolism and reducing cardiovascular disease burden. In this study, we investigated the impact of ASGR1 deficiency (ASGR1-/-) on atherosclerosis by evaluating its effects on plaque formation, lipid metabolism, circulating immunoinflammatory response, and circulating N-glycome under the hypercholesterolemic condition in ApoE-deficient mice. After 16 weeks of a western-type diet, ApoE-/-/ASGR1-/- mice presented lower plasma cholesterol and triglyceride levels compared to ApoE-/-. This was associated with reduced atherosclerotic plaque area and necrotic core formation. Interestingly, ApoE-/-/ASGR1-/- mice showed increased levels of circulating immune cells, increased AST/ALT ratio, and no changes in the N-glycome profile and liver morphology. The liver of ApoE-/-/ASGR1-/- mice, however, presented alterations in the metabolism of lipids, xenobiotics, and bile secretion, indicating broader alterations in liver homeostasis beyond lipids. These data suggest that improvements in circulating lipid metabolism and atherosclerosis in ASGR1 deficiency is paralleled by a deterioration of liver injury. These findings point to the need for additional evaluation before considering ASGR1 as a pharmacological target for dyslipidemia and cardiovascular disorders.PMID:39616371 | DOI:10.1186/s12933-024-02507-5

Tailored impact of dietary fibers on gut microbiota: a multi-omics comparison on the lean and obese microbial communities

Sat, 30/11/2024 - 12:00
Microbiome. 2024 Nov 30;12(1):250. doi: 10.1186/s40168-024-01975-x.ABSTRACTBACKGROUND: Previous studies have shown that microbial communities differ in obese and lean individuals, and dietary fiber can help reduce obesity-related conditions through diet-gut microbiota interactions. However, the mechanisms by which dietary fibers shape the gut microbiota still need to be elucidated. In this in vitro study, we examined how apple fibers affect lean and obese microbial communities on a global scale. We employed a high-throughput micro-matrix bioreactor system and a multi-omics approach to identify the key microorganisms and metabolites involved in this process.RESULTS: Initially, metagenomics and metabolomics data indicated that obese and lean microbial communities had distinct starting microbial communities. We found that obese microbial community had different characteristics, including higher levels of Ruminococcus bromii and lower levels of Faecalibacterium prausnitzii, along with an increased Firmicutes:Bacteroides ratio. Afterward, we exposed obese and lean microbial communities to an apple as a representative complex food matrix, apple pectin as a soluble fiber, and cellulose as an insoluble fiber. Dietary fibers, particularly apple pectin, reduced Acidaminococcus intestini and boosted Megasphaera and Akkermansia in the obese microbial community. Additionally, these fibers altered the production of metabolites, increasing beneficial indole microbial metabolites. Our results underscored the ability of apple and apple pectin to shape the obese gut microbiota.CONCLUSION: We found that the obese microbial community had higher branched-chain amino acid catabolism and hexanoic acid production, potentially impacting energy balance. Apple dietary fibers, especially pectin, influenced the obese microbial community, altering both species and metabolites. Notably, the apple pectin feeding condition affected species like Klebsiella pneumoniae and Bifidobacterium longum. By using genome-scale metabolic modeling, we discovered a mutualistic cross-feeding relationship between Megasphaera sp. MJR8396C and Bifidobacterium adolescentis. This in vitro study suggests that incorporating apple fibers into the diets of obese individuals can help modify the composition of gut bacteria and improve metabolic health. This personalized approach could help mitigate the effects of obesity. Video Abstract.PMID:39616358 | PMC:PMC11608498 | DOI:10.1186/s40168-024-01975-x

Integrative multi-omics analysis to gain new insights into COVID-19

Sat, 30/11/2024 - 12:00
Sci Rep. 2024 Nov 30;14(1):29803. doi: 10.1038/s41598-024-79904-z.ABSTRACTMultidimensional host and viral factors determine the clinical course of COVID-19. While the virology of the disease is well studied, investigating host-related factors, including genome, transcriptome, metabolome, and exposome, can provide valuable insights into the underlying pathophysiology. We conducted integrative omics analyses to explore their intricate interplay in COVID-19. We used data from the UK Biobank (UKB), and employed single-omics, pairwise-omics, and multi-omics models to illustrate the effects of different omics layers. The dataset included COVID-19 phenotypic data as well as genome, imputed-transcriptome, metabolome and exposome data. We examined the main, interaction effects and correlations between omics layers underlying COVID-19. Single-omics analyses showed that the transcriptome (derived from the coronary artery tissue) and exposome captured 3-4% of the variation in COVID-19 susceptibility, while the genome and metabolome contributed 2-2.5% of the phenotypic variation. In the omics-exposome model, where individual omics layers were simultaneously fitted with exposome data, the contributions of genome and metabolome were diminished and considered negligible, whereas the effects of the transcriptome showed minimal change. Through mediation analysis, the findings revealed that exposomic factors mediated about 60% of the genome and metabolome's effects, while having a relatively minor impact on the transcriptome, mediating only 7% of its effects. In conclusion, our integrative-omics analyses shed light on the contribution of omics layers to the variance of COVID-19.PMID:39616224 | PMC:PMC11608341 | DOI:10.1038/s41598-024-79904-z

The cross-talk between the metabolome and microbiome in a double-hit neonatal rat model of bronchopulmonary dysplasia

Sat, 30/11/2024 - 12:00
Genomics. 2024 Nov 28:110969. doi: 10.1016/j.ygeno.2024.110969. Online ahead of print.ABSTRACTBronchopulmonary dysplasia (BPD), a chronic lung disease in preterm infants, is associated with inflammation and high oxygen exposure. However, the effects of antenatal inflammation and extended hyperoxia on the metabolome and microbiome remain unclear. In this study, pregnant rats received lipopolysaccharide or saline injections on gestational day 20 and were exposed to either 21 % or 80 % oxygen for 4 weeks post-birth. Analysis revealed an increase in Firmicutes, Proteobacteria, and Actinobacteria, with a decrease in Bacteroidetes in BPD rats. Metabolomic analysis identified 78 altered metabolites, primarily lipids, with enrichment in arginine biosynthesis, sphingolipid metabolism, and primary bile acid biosynthesis in BPD rats. Integration analysis revealed strong correlations between intestinal microbiota and metabolites in BPD rats. These findings underscore the impact of antenatal inflammation and prolonged hyperoxia on gut microbiota and serum metabolome, suggesting their role in BPD pathogenesis.PMID:39615804 | DOI:10.1016/j.ygeno.2024.110969

Metabolome-Wide Mendelian Randomization Assessing the Causal Relationship Between Blood Metabolites and Primary Ovarian Insufficiency

Sat, 30/11/2024 - 12:00
Clin Nutr ESPEN. 2024 Nov 28:S2405-4577(24)01522-5. doi: 10.1016/j.clnesp.2024.11.013. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Primary ovarian insufficiency (POI) is a significant clinical syndrome that leads to female infertility, and its incidence continues to increase. We used metabolome-specific Mendelian randomization (MR) to identify causally associated metabolites and explore the relationship between candidate metabolites and upstream genetic variations.METHODS: The primary MR analysis utilized the inverse variance weighted (IVW) method as the primary approach to assess the causal relationship between exposure and POI. Multiple sensitivity analyses included MR-Egger, weighted median, and weighted mode methods.RESULTS: After using genetic variants as probes, we identified 27 metabolites of 278 that are associated with the risk of POI, including dodecanedioate (OR 0.052, 95% CI 0.010 - 0.265; P < 0.001), adrenate (OR 0.113, 95% CI 0.016 - 0.822; P = 0.031), indolepropionate (OR 0.174, 95% CI 0.051 - 0.593; P = 0.005), homocitrulline (OR 0.194, 95% CI 0.051 - 0.741; P = 0.016), and 3-methylhistidine (OR 0.404, 95% CI 0.193 - 0.848; P = 0.017). Our study indicated the presence of heterogeneity; therefore, we employed the IVW random-effects model as the primary approach. KEGG pathway enrichment analysis identified six significant metabolic pathways, primarily including biosynthesis of unsaturated fatty acids, phenylalanine, tyrosine and tryptophan biosynthesis, aminoacyl-tRNA biosynthesis, linoleic acid metabolism, valine, leucine and isoleucine biosynthesis, ubiquinone and other terpenoid-quinone biosynthesis.CONCLUSIONS: By integrating genomics and metabolomics, this study provides novel insights into the causal relationship linking circulating metabolites and the onset of POI.PMID:39615787 | DOI:10.1016/j.clnesp.2024.11.013

Physiological activities, transcriptomes and metabolomes of Pyropia yezoensis conchocelis unveil the roles of pyPGK, pyBCKDHA, and pyDLD in response to freshwater soaking

Sat, 30/11/2024 - 12:00
Int J Biol Macromol. 2024 Nov 28:138193. doi: 10.1016/j.ijbiomac.2024.138193. Online ahead of print.ABSTRACTFreshwater soaking of the conchocelis is often used to reduce yellow spot, white spot, and mud red disease in Pyropia yezoensis. However, the understanding of physiological, transcriptomic, and metabolomic changes for the conchocelis under freshwater stress remains limited. Here, we comprehensively explored the dynamic changes of physiological activities, transcriptomes, and metabolomes of the conchocelis under three points of freshwater stress (0 h, 4 h, and 24 h) and one point of seawater recovery (R2h). We found that the content of photosynthetic pigments, soluble proteins, and photosynthesis performance significantly responded to freshwater stress. Metabolomic analysis identified a total of 24 metabolites, including 15 DAMs, suggesting the metabolites changes in the conchocelis in response to freshwater stress. Additionally, comparative transcriptome and metabolome analyses identified a black co-expression module that was strongly correlated with the DAMs. Furthermore, this module was predominantly enriched in carbohydrate and amino acid metabolism pathways. We found that PyDLD, PyPGK, and PyBCKDHA were key genes in hub-networks, which are potentially involved in changes of leucine, valine, isoleucine, lactate, and floridoside during freshwater stress. These findings reveal the genetic basis of the dynamic changes of physiological activities, transcriptome, and metabolome in the Py. yezoensis conchocelis during freshwater soaking for disease control.PMID:39615718 | DOI:10.1016/j.ijbiomac.2024.138193

Metabolic control of Luteinizing Hormone-responsive ovarian steroidogenesis

Sat, 30/11/2024 - 12:00
J Biol Chem. 2024 Nov 28:108042. doi: 10.1016/j.jbc.2024.108042. Online ahead of print.ABSTRACTThe pituitary gonadotropin luteinizing hormone (LH) is the primary stimulus for ovulation, luteal formation and progesterone synthesis, regardless of species. Despite increased awareness of intracellular signaling events initiating the massive production of progesterone during the reproductive cycle and pregnancy, critical gaps exist in our knowledge of the metabolic and lipidomic pathways required for initiating and maintaining luteal progesterone synthesis. Using untargeted metabolomics and metabolic flux analysis in primary steroidogenic luteal cells, evidence is provided for rapid LHCGR-stimulation of metabolic pathways leading to increased glycolysis and oxygen consumption. Treatment with LH stimulated post-translational modifications of enzymes involved in de novo lipogenesis. Mechanistic studies implicated a crucial role for de novo fatty acid synthesis and fatty acid oxidation in energy homeostasis, LHCGR/PKA signaling, and, consequently, progesterone production. These findings reveal novel hormone-sensitive metabolic pathways essential for maintaining LHCGR/PKA signaling and steroidogenesis. Understanding hormonal control of metabolic pathways in steroidogenic cells may help elucidate approaches for improving ovarian function and successful reproduction or identifying metabolic targets for developing nonhormonal contraceptives.PMID:39615688 | DOI:10.1016/j.jbc.2024.108042

Metabolomics combined with biochemical analyses revealed phenolic profiles and antioxidant properties of rapeseeds

Sat, 30/11/2024 - 12:00
Food Chem. 2024 Nov 26;466:142250. doi: 10.1016/j.foodchem.2024.142250. Online ahead of print.ABSTRACTPhenolic compounds, one of the most crucial lipid concomitants in rapeseed, have garnered heighten attention due to their numerous health benefits. Therefore, efficiently characterizing the phenolic profile of rapeseed is paramount for discerning their potential bioactivities. This study employed untargeted metabolomics in conjunction with molecular networking to trace the phenolic composition across three rapeseed genotypes. A total of 117 phenolic compounds were identified in rapeseed by mass spectrometry under positive and negative ionization modes, including 36 flavonoids, 23 coumarins, 12 phenolic acids, 10 lignans, 4 stilbenes, 4 diarylheptanes, 1 tannin, and several other phenolic constituents. Biochemical analyses revealed that Brassica napus rapeseed typically exhibited the highest total phenolic content and total flavonoid content as well as the strongest antioxidant capacity among three rapeseed genotypes. Through correlation analysis, 17 potential antioxidant phenolic compounds were tentatively screened from rapeseed, supporting the development and utilization of natural antioxidants from rapeseed.PMID:39615359 | DOI:10.1016/j.foodchem.2024.142250

Effects of different drying methods on the chemical components and activities of Taihang chrysanthemum (Opisthopappus taihangensis)

Sat, 30/11/2024 - 12:00
Food Chem. 2024 Nov 26;466:142262. doi: 10.1016/j.foodchem.2024.142262. Online ahead of print.ABSTRACTAlthough the health benefits of chrysanthemums have been widely studied, there is a paucity of knowledge regarding Taihang chrysanthemum (Opisthopappus taihangensis). This study compared indoor shade drying, heat drying and freeze drying on the chemical profile and health-related activities of O. taihangensis. UPLC-Q-TOF-MS and other assays were used to evaluate changes in composition and antioxidant, antibacterial and enzyme inhibitory activities. Different drying methods significantly affected compositions and bioactivities of O. taihangensis. Lipids, phenylpropanoids and polyketides were the most abundant. Freeze-drying maintained bioactive compounbds like phenylpropanoids and superior antioxidant activities. Freeze-dried O. taihangensis also displayed robust antibacterial activity against Streptococcus hemolyticus-β and effective inhiition of pancreatic lipase. These results suggest O. taihangensis is a useful source of functional compounds.PMID:39615349 | DOI:10.1016/j.foodchem.2024.142262

Cord plasma metabolomic signatures of prenatal per- and polyfluoroalkyl substance (PFAS) exposures in the Boston Birth Cohort

Sat, 30/11/2024 - 12:00
Environ Int. 2024 Nov 15;194:109144. doi: 10.1016/j.envint.2024.109144. Online ahead of print.ABSTRACTBACKGROUND: Prenatal per- and polyfluoroalkyl substance (PFAS) exposures are associated with adverse offspring health outcomes, yet the underlying pathological mechanisms are unclear. Cord blood metabolomics can identify potentially important pathways associated with prenatal PFAS exposures, providing mechanistic insights that may help explain PFAS' long-term health effects.METHODS: The study included 590 mother-infant dyads from the Boston Birth Cohort. We measured PFAS in maternal plasma samples collected 24-72 h after delivery and metabolites in cord plasma samples. We used metabolome-wide association studies and pathway enrichment analyses to identify metabolites and pathways associated with individual PFAS, and quantile-based g-computation models to examine associations of metabolites with the PFAS mixture. We used False Discovery Rate to account for multiple comparisons.RESULTS: We found that 331 metabolites and 18 pathways were associated with ≥ 1 PFAS, and 38 metabolites were associated with the PFAS mixture, predominantly amino acids and lipids. Amino acids such as alanine and lysine and their pathways, crucial to energy generation, biosynthesis, and bone health, were associated with PFAS and may explain PFAS' effects on fetal growth restriction. Carnitines and carnitine shuttle pathway, associated with 7 PFAS and the PFAS mixture, are involved in mitochondrial fatty acid β-oxidation, which may predispose higher risks of fetal and child growth restriction and cardiovascular diseases. Lipids, such as glycerophospholipids and their related pathway, can contribute to insulin resistance and diabetes by modulating transporters on cell membranes, participating in β-cell signaling pathways, and inducing oxidative damage. Neurotransmission-related metabolites and pathways associated with PFAS, including cofactors, precursors, and neurotransmitters, may explain the PFAS' effects on child neurodevelopment. We observed stronger associations between prenatal PFAS exposures and metabolites in males.CONCLUSIONS: This prospective birth cohort study contributes to the limited literature on potential metabolomic perturbations for prenatal PFAS exposures. Future studies are needed to replicate our findings and link prenatal PFAS associated metabolomic perturbations to long-term child health outcomes.PMID:39615256 | DOI:10.1016/j.envint.2024.109144

Understanding the possible cellular responses in plants under micro(nano)-plastic (MNPs): Balancing the structural harmony with functions

Sat, 30/11/2024 - 12:00
Sci Total Environ. 2024 Nov 28;957:177732. doi: 10.1016/j.scitotenv.2024.177732. Online ahead of print.ABSTRACTThe harmful impacts of micro(nano)-plastics (MNPs) on plants have gained significant attention in the last decades. Plants have a greater tendency to aggregate positively charged (+ve) MNPs on leaf surfaces and root tips, and it can be more challenging to enter the plant body than the negatively charged (-ve) MNPs. MNPs <20 nm can directly cross the cell wall and enter mainly via leaf stomata and root crack portion. Additionally, plants with aerenchyma tissue or higher water requirement might be more vulnerable to MNPs as well as environmental factors also affected MNPs uptake like porosity and structure (i.e. crack of soil) of soil, wind speed, etc. The subsequent translocation of MNPs hamper regular morphological, physiological, and biochemical functions by causing oxidative stress, altering several plant metabolic pathways, reducing the rate of photosynthesis and nutrient intake, etc. These induce cellular toxicity and chromosomal alteration; as a result, the total biomass and productivity reduce vigorously. However, there is a knowledge gap regarding MNPs' uptake by plants and related variables affecting phytotoxicity at the omics levels. So, the present literature review represents a comprehensive theoretical framework that includes genomics, transcriptomics, miRNAomics, proteomics, metabolomics, and ionomics/metallomics, which is established to understand the effects of MNPs on plants at the molecular level. As well as it will also help in further studies of the research community in the future because this field is still in the preliminary stages due to a lack of study.PMID:39615174 | DOI:10.1016/j.scitotenv.2024.177732

The central role of creatine and polyamines in fetal growth restriction

Sat, 30/11/2024 - 12:00
FASEB J. 2024 Dec 15;38(23):e70222. doi: 10.1096/fj.202401946R.ABSTRACTPlacental insufficiency often correlates with fetal growth restriction (FGR), a condition that has both short- and long-term effects on the health of the newborn. In our study, we analyzed placental tissue from infants with FGR and from infants classified as small for gestational age (SGA) or appropriate for gestational age (AGA), performing comprehensive analyses that included transcriptomics and metabolomics. By examining villus tissue biopsies and 3D trophoblast organoids, we identified significant metabolic changes in placentas associated with FGR. These changes include adaptations to reduced oxygen levels and modifications in arginine metabolism, particularly within the polyamine and creatine phosphate synthesis pathways. Specifically, we found that placentas with FGR utilize arginine to produce phosphocreatine, a crucial energy reservoir for ATP production that is essential for maintaining trophoblast function. In addition, we found polyamine insufficiency in FGR placentas due to increased SAT1 expression. SAT1 facilitates the acetylation and subsequent elimination of spermine and spermidine from trophoblasts, resulting in a deficit of polyamines that cannot be compensated by arginine or polyamine supplementation alone, unless SAT1 expression is suppressed. Our study contributes significantly to the understanding of metabolic adaptations associated with placental dysfunction and provides valuable insights into potential therapeutic opportunities for the future.PMID:39614665 | DOI:10.1096/fj.202401946R

Metabolomics reveals that phosphatidylethanolamine can alleviate the toxicity of silica nanoparticles in human lung A549 cells

Sat, 30/11/2024 - 12:00
Toxicol Ind Health. 2024 Nov 29:7482337241304166. doi: 10.1177/07482337241304166. Online ahead of print.ABSTRACTSilica nanoparticles (SiNPs) are widely utilized in occupational settings where they can cause lung damage through inhalation. The objective of this research was to explore the metabolic markers of SiNPs-induced toxicity on A549 cells by metabolomics and provide a foundation for studying nanoparticle-induced lung toxicity. Metabolomics analysis was employed to analyze the metabolites of SiNPs-treated A549 cells. LASSO regression was applied for selection, and protective measure experiments were conducted to validate the efficacy of selected potential toxicity mitigators. After SiNPs treatment, 23 differential metabolites were identified, including lipids, nucleotides, and organic oxidants. Pathway analysis revealed involvement in various biological processes. LASSO regression further identified six metabolites significantly associated with SiNPs toxicity. Notably, phosphatidylethanolamine (PE (14:1(9Z)/14:0)) showed enrichment in six significant metabolic pathways and with an AUC of 1 in the ROC curve. Protective measure experiments verified its protective effect on A549 cells and demonstrated its considerable inhibition of SiNPs-induced cytotoxicity. This study elucidated SiNPs-induced cytotoxicity on A549 cells and identified PE as a potential toxicity mitigator. These findings contribute to understanding the mechanisms of nanoparticle-induced lung toxicity and inform occupational health preventive strategies.PMID:39614625 | DOI:10.1177/07482337241304166

Metabolic marker-assisted genomic prediction improves hybrid breeding

Sat, 30/11/2024 - 12:00
Plant Commun. 2024 Nov 28:101199. doi: 10.1016/j.xplc.2024.101199. Online ahead of print.ABSTRACTHybrid breeding is widely acknowledged as the most effective method for increasing crop yield, particularly in maize and rice. However, a major challenge in hybrid breeding is selecting desirable combinations from a vast pool of potential crosses. Genomic selection (GS) has emerged as a powerful tool to tackle this challenge, but its success in practical breeding depends on prediction accuracy. Several strategies have been explored to enhance the prediction accuracy for complex traits, such as incorporating functional markers and multi-omics data. Metabolome-wide association studies (MWAS) help identify metabolites closely linked to phenotype, known as metabolic markers. However, the use of preselected metabolic markers from parental lines to predict hybrid performance has not yet been explored. In this study, we developed a novel approach called metabolic marker-assisted genomic prediction (MM_GP) that incorporates significant metabolites identified from MWAS into GS models to improve the accuracy of genomic hybrid prediction. In maize and rice hybrid populations, MM_GP outperformed GP for all traits, regardless of the methods used (GBLUP or XGBoost). On average, MM_GP yielded 4.6% and 13.6% higher predictive abilities compared to GP in maize and rice, respectively. Additionally, MM_GP could match or even surpass the predictive ability of M_GP (integrated genomic-metabolomic prediction) for most traits. Notably, integrating only six metabolic markers significantly related to multiple traits resulted in a 5.0% and 3.1% higher average predictive ability than GP and M_GP in maize, respectively. With the advancement of high-throughput metabolomics technologies and prediction models, this approach holds great promise to revolutionize genomic hybrid breeding by enhancing its accuracy and efficiency.PMID:39614617 | DOI:10.1016/j.xplc.2024.101199

Microbiota-derived succinic acid mediates attenuating effect of dietary tomato juice supplementation on steatohepatitis through enhancing intestinal barrier

Sat, 30/11/2024 - 12:00
Food Res Int. 2024 Nov;196:115123. doi: 10.1016/j.foodres.2024.115123. Epub 2024 Sep 21.ABSTRACTThe hepatoprotective potential of tomato juice (TJ) has been reported in chronic liver models, and its potential prebiotic properties may be key to its preventative effects. However, the mechanistic role of the gut microbiota and its derived metabolites in ameliorating nonalcoholic steatohepatitis (NASH) via TJ remains unclear. In this study, we explored how TJ regulates gut microbiota and succinic acid (SA) to restore intestinal barrier function and thus suppress NASH progression. TJ supplementation effectively reduced serum lipid concentrations, alleviated endotoxin levels, and suppressed activation of the endotoxin-TLR4-NF-κB pathway in methionine-choline-deficient (MCD) diet-induced NASH mice. TJ restored the MCD diet-induced gut microbiota dysbiosis, increased the abundance of short-chain fatty acid and SA-producing bacteria (Bifidobacterium, Ileibacterium, Odoribacter, and Parasutterella) and enhanced the expression of intestinal barrier-associated proteins (E-cadherin, Claudin-1, MUC-2, and ZO-1). The hepatoprotective and enteroprotective effects of TJ were abolished in an antibiotic-treated mouse model, underscoring the pivotal role of the gut microbiota in the beneficial effects of TJ on NASH. Fecal metabolomics demonstrated that TJ significantly upregulated the tricarboxylic acid cycle, pyruvate metabolism, and butanoate metabolism pathways, increasing levels of butyric acid (BA) and SA-metabolites associated with reduced hepatic steatosis and intestinal damage. We further found that the physiological concentration of SA, rather than BA, could reduce pro-inflammatory cytokines (TNF-α and IL-6) levels and enhance mucin proteins and tight junction markers in the LPS-induced colon cell line LS174T. This study uncovers new mechanisms by which TJ prevents NASH, highlighting the potential of TJ and SA as effective dietary supplements for patients with chronic liver diseases.PMID:39614583 | DOI:10.1016/j.foodres.2024.115123

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