PubMed

Neurobiol Dis. 2024 Nov 29:106747. doi: 10.1016/j.nbd.2024.106747. Online ahead of print.ABSTRACTAlzheimer's disease (AD) affects more women than men. Although women live longer than men, it is not longevity alone, but other factors, including metabolic changes, that contribute to the higher risk of AD in women. Metabolic pathways have been implicated in AD progression, but studies to date examined targeted pathways, leaving many metabolites unmeasured. Sex is often a neglected biological variable, and most metabolomic studies were not designed to investigate sex differences in metabolomic profiles. Here, we performed untargeted metabolomic profiling of sera from male and female patients with mild cognitive impairment (MCI), a common precursor to AD, and matched controls. We discovered significant metabolic changes in individuals with MCI, and found several pathways that were strongly associated with sex. Peptide energy metabolism demonstrated sexual dimorphism. Lipid pathways exhibited the strongest differences between female and male MCI patients, including specific phosphatidylcholine lipids, lysophospholipids, long-chain fatty acids, and monoacylglycerols. 1-palmitoleoyl glycerol and 1-arachidonoyl glycerol were higher in female MCI subjects than in male MCI subjects with no differences between control males and females. Conversely, specific dicarboxylic fatty acids were lower in female MCI subjects than male MCI subjects. In cultured astrocytes, 1-arachidonoyl glycerol promoted phosphorylation of the transcriptional regulator sphingosine kinase 2, which was inhibited by the transient receptor potential vanilloid 1 receptor antagonists, as well as chromatin remodelling. Overall, we identified novel sex-specific metabolites in MCI patients that could serve as biomarkers of MCI in both sexes, help further define AD etiology, and reveal new potential prevention strategies for AD.PMID:39617329 | DOI:10.1016/j.nbd.2024.106747

J Hepatol. 2024 Nov 29:S0168-8278(24)02740-5. doi: 10.1016/j.jhep.2024.11.038. Online ahead of print.NO ABSTRACTPMID:39617134 | DOI:10.1016/j.jhep.2024.11.038

J Ethnopharmacol. 2024 Nov 29:119176. doi: 10.1016/j.jep.2024.119176. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Quanduzhong capsule (QDZ), derived from Eucommia ulmoides Oliv. has been traditionally used in Chinese medicine for its beneficial effects on musculoskeletal health. Its clinical application has extended to conditions such as spontaneous hypertension combined with knee osteoarthritis (SKOA). However, the specific mechanisms by which QDZ alleviates symptoms and improves outcomes in this complex condition remain to be fully elucidated.AIM OF THE STUDY: This study aims to evaluate the therapeutic potential of QDZ in treating SKOA. By performing serum proteomics and metabolomics, we seek to explore the related biological pathways and elucidate the mechanisms underlying QDZ's effects on SKOA.MATERIALS AND METHODS: Serum samples from control, spontaneous hypertension (SHR), SKOA, and SKOA treated with QDZ groups were analyzed using data-independent acquisition-based proteomics to identify differentially expressed proteins. Serum levels of angiotensin II, norepinephrine, endothelin-1, classical pro-inflammatory factors such as macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-1 beta were measured. Additionally, serum metabolomics was performed to examine the changes in metabolite profiles. Correlation analysis was conducted to link changed proteins and metabolites with key pathways affected by QDZ.RESULTS: Proteomics analysis revealed significant alterations in serum protein expression between control, SHR, and SKOA groups, with changes in pathways related to immune regulation, and vascular function. KEGG enrichment analysis highlighted pathways such as endocytosis, synaptic vesicle cycling, and immune responses were enriched in SKOA group compared with control group. QDZ treatment significantly modulated above pathways and reduced inflammatory and cardiovascular markers which were upregulated in SKOA group. Metabolomics analysis showed that QDZ reversed SKOA-induced changes in amino acid and organic acid metabolism, affecting pathways including valine, leucine, and isoleucine metabolism, as well as the TCA cycle. Correlation analysis revealed significant relationships between key proteins and metabolites, underscoring the integrated role of immune and metabolic pathways in QDZ's effects.CONCLUSIONS: Our results indicate QDZ has a significant therapeutic potential for SKOA by modulating both protein and metabolite profiles associated with inflammation, vascular dysfunction, and metabolic imbalance. Our findings provide insights into the mechanisms through which QDZ exerts its effects and support its use as a promising treatment for SKOA. This study highlights the impact of QDZ on proteomic and metabolomic alterations, offering a basis for its broader application in treating SKOA.PMID:39617089 | DOI:10.1016/j.jep.2024.119176

J Ethnopharmacol. 2024 Nov 29:119128. doi: 10.1016/j.jep.2024.119128. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Pioglitazone (PIO) was an anti type 2 diabetes (T2D) agent but caused bone loss and bone marrow fat accumulation. Puerarin (PUE) was a natural component of herbal medicine extracted from Pueraria lobata (Willd.) Ohwi and reduced glycemia and improved bone mass as a supplementary drug. A combination of PIO and PUE might be good for maintaining bone mass and blood glucose.AIM OF THE STUDY: We aimed to elucidate the potential correlation and underlying mechanisms of dietary supplement PUE in reducing side effects caused by PIO.MATERIALS AND METHODS: In vitro, alkaline phosphatase (ALP) staining, alizarin S (ARS) staining and qRT-PCR were performed to detect the osteogenesis activity in MC3T3-E1 cells. In vivo, we established the T2D model by treating C57BL6/J mice with high-fat diets and streptozotocin (STZ). Micro-CT, hematoxylin and eosin (H&E) staining and tartrate-resistant acid phosphatase (TRAcP) staining were performed to observe the difference in skeletal phenotype. Serum metabolomics and 16S rRNA amplicon sequencing were applied to analyze the potential effect of the combination of PIO and PUE.RESULTS: We showed that the PUE could increase ALP activity and mineralization nodes of MC3T3-E1 with PIO. PIO could aggravate bone loss but PUE alleviated the effect caused by PIO in T2D mice. PUE promoted alpha-linolenic acid metabolism and glycerophospholipid metabolism, and affected the alpha diversity of the gut microbiome by regulating the genera of Alloprevotella, Fusobacterium, Rodentibacter, etc. Correlation analysis indicated that sphingosine-1-phosphate, nonadecylic acid, and margaric acid were associated with the effect of PUE.CONCLUSIONS: Taken together, we demonstrated that PIO combined with PUE was able to lower blood sugar levels without causing bone loss. The effect of PUE mainly correlated with the genua of Alloprevotella, Fusobacterium, Rodentibacter, and Alistipes. Also, alpha-linolenic acid metabolism and glycerophospholipid metabolism were major targets of PUE.PMID:39617084 | DOI:10.1016/j.jep.2024.119128

J Ethnopharmacol. 2024 Nov 29:119166. doi: 10.1016/j.jep.2024.119166. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Chinese materia medica (CMM) has a long history and extensive experience in treating ischemic stroke. Wen Ezhu, the rhizome of Curcuma wenyujin Y.H. Chen et C. Ling, is renowned for promoting blood circulation, dispersing blood stasis, alleviating pain, and eliminating masses. Promoting blood circulation and removing blood stasis are essential principles in Traditional Chinese Medicine for treating stroke. Consequently, Wen Ezhu is frequently used in clinical practice as a key CMM for treating stroke. The Elemene active fraction (ELE), a sesquiterpene compound extracted from Wen Ezhu, primarily consists of β-Elemene. It also contains β-Caryophyllene, γ-Elemene, and δ-Elemene isomers. ELE has shown potential pharmacological effects in various diseases, including ischemic stroke. However, its precise mechanism of action in treating stroke remains to be confirmed.AIM OF THE STUDY: To explore the therapeutic potential of ELE in acute ischemic stroke and elucidate its underlying mechanisms.MATERIALS AND METHODS: A rat model of middle cerebral artery occlusion reperfusion (MCAO/R) was used to evaluate ELE's effects. Therapeutic efficacy was assessed through mNSS scoring, magnetic resonance imaging (MRI), tetrazolium chloride (TTC) staining, Hematoxylin and eosin (H&E), and Nissl staining. Non-targeted metabolomics identified key pathways, confirmed using biochemical analysis, immunohistochemistry, and Western blotting. ROS levels and apoptosis-related proteins were also evaluated.RESULTS: Our findings show that ELE administration significantly reduced the cerebral infarct area and lowered modified neurological severity scores (mNSS) in animals, indicating a strong neuroprotective effect. Metabolomics results highlight the glutathione (GSH) metabolic pathway as a key mechanism through which ELE exerts its therapeutic effects. Specifically, ELE upregulates glutathione reductase (GR) protein expression and downregulates glutathione peroxidase (GPX) expression. The regulatory process of ELE decreases oxidized glutathione (GSSG) levels and increases GSH levels, effectively reducing oxidative stress damage (lower reactive oxygen species levels) during CI/RI. This results in the downregulation of the pro-apoptotic protein Bax and the upregulation of the pro-survival protein Bcl-2, thus reducing neuronal apoptosis.CONCLUSIONS: ELE protects neurons in MCAO/R rats through the GSH metabolism pathway, balancing GSH and GSSG levels to mitigate oxidative stress and enhance neuroprotection in cerebral ischemia/reperfusion injury.PMID:39617083 | DOI:10.1016/j.jep.2024.119166

Microb Physiol. 2024 Nov 29:1-18. doi: 10.1159/000542892. Online ahead of print.ABSTRACTINTRODUCTION: The low yield of bioflocculants has been a bottleneck problem that limits their industrial applications. Understanding the metabolic mechanism of bacteria that produce bioflocculants, could provide valuable insights and strategies to directly regulate their yield in future.METHODS: To investigate the change of metabolites in the process of bioflocculant production by a biomass-degrading bacterium, Pseudomonas boreopolis GO2, an untargeted metabolome analysis was performed.RESULTS: The results showed that metabolites significantly differed during the fermentation process when corn stover was used as the sole carbon source. The differential metabolites were divided into four co-expression modules based on the weighted gene co-expression network analysis. Among them, a module (yellow module) was closely related to the flocculating efficiency, and the metabolites in this module were mainly involved in carbohydrate, lipid and amino acid metabolism. The top 30 metabolites with the highest degree in the yellow module were identified as hub metabolites for bioflocculants' production. Finally, 10 hub metabolites were selected to perform the additional experiments, and the addition of L-rhamnose, tyramine, tryptophan, and glutaric acid alone all could significantly improve the flocculating efficiency of GO2 strain.CONCLUSION: These results indicated that the hub metabolites were key for bioflocculant production in GO2 strain, and could help guide the improvement of high-efficiency and low-cost bioflocculant production.PMID:39616990 | DOI:10.1159/000542892

J Hazard Mater. 2024 Nov 29;483:136693. doi: 10.1016/j.jhazmat.2024.136693. Online ahead of print.ABSTRACTThe harmful influence caused by cadmium (Cd) to agriculture is severe and enduring. Efforts to reduce the damage by Cd to crop is an important topic. In this study, we investigated the effect of MgO NPs on tobacco seedlings' growth under Cd stress and explored its mechanism. Results showed Cd inhibited seedling growth, but MgO NPs alleviated this toxicity. With MgO NPs, shoot and root fresh weight increased by 35.12 % and 45.73 %. This was mainly due to MgO NPs reducing Cd accumulation by 40 % in root and 20.48 % in shoot compared to Cd treatment. MgO NPs not only reduced Cd accumulation but redistributed it to inactive cell walls: up to 55 % in shoot and 22 % in root (compared to 47 % and 22 % in Cd treatment). The primary mechanism was the change in cell wall's main ingredient: lignin. MgO NPs increased lignin content by 50.62 % compared to Cd treatment. To further investigate the underlying molecular mechanism, multi-omics analysis was conducted. Comparing Cd + MgO NPs with Cd, 1358 DEGs (694 up, 664 down) and 160 DEMs (44 up, 116 down) were identified. Furthermore, we identified ABA-regulated phenylpropanoid pathway as the key mechanism for lignin synthesis. MgO NPs boosted ABA levels by 6.72 % compared to Cd treatment. The multi-omics analysis revealed upregulation of ABA synthesis and signal transduction, leading to increased phenylpropanoid pathway metabolites and gene expressions. Notably, POD, a key enzyme, increased by 92.05 %. It was concluded that MgO NPs represent a highly efficient alternative for enhancing plant resistance to Cd.PMID:39616846 | DOI:10.1016/j.jhazmat.2024.136693

Plant Physiol Biochem. 2024 Nov 26;219:109334. doi: 10.1016/j.plaphy.2024.109334. Online ahead of print.ABSTRACTAbiotic stresses, such as extreme temperatures, drought, and salinity, significantly affect plant growth and productivity. Among these, cold stress is particularly detrimental, impairing cellular processes and leading to reduced crop yields. In recent years, stress-associated proteins (SAPs) containing A20 and AN1 zinc-finger domains have emerged as crucial regulators in plant stress responses. However, the functions of SAPs in tobacco plants remain unclear. Here, we isolated Nicotiana tabacum SAP9 (NtSAP9), whose expression was induced by cold treatment, based on RNA-sequences data. Knock down of NtSAP9 expression reduced freezing tolerance, while overexpression conferred freezing tolerance in transgenic tobacco plants, as indicated by relative electrolytic leakage and photosystem II photochemical efficiency. Untargeted metabolomics via liquid chromatography-tandem mass spectrometry revealed distinct metabolic profiles between WT and NtSAP9-overexpressing tobacco plants under normal and low temperature conditions. Upregulation of amino acids like D-Glutamine, DL-Glutamine, and O-Acetyl-L-serine suggests NtSAP9 enhances cold tolerance. Further expression analysis by quantitative real-time PCR indicated that NtSAP9 participates in cold stress response possibly through amino acid synthesis-related genes expression, such as glutamine synthetase and glutamate dehydrogenase. These findings improve our understanding of SAP proteins in tobacco's response to cold stress.PMID:39616799 | DOI:10.1016/j.plaphy.2024.109334

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

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

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

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

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

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

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

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

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

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

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

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