PubMed

Plants (Basel). 2023 May 15;12(10):1987. doi: 10.3390/plants12101987.ABSTRACTCnidoscolus aconitifolius (CA) and Porophyllum ruderale (PR) are representative edible plants that are a traditional food source in Mexico. This research aimed to analyze the phytochemical composition and untargeted metabolomics analysis of CA and PR and evaluate their antiproliferative effect in vitro. The phytochemical composition (UPLC-DAD-QToF/MS-ESI) identified up to 38 polyphenols and selected organic acids that were clustered by the untargeted metabolomics in functional activities linked to indolizidines, pyridines, and organic acids. Compared with PR, CA displayed a higher reduction in the metabolic activity of human SW480 colon adenocarcinoma cells (LC50: 10.65 mg/mL), and both extracts increased the total apoptotic cells and arrested cell cycle at G0/G1 phase. PR increased mRNA Apc gene expression, whereas both extracts reduced mRNA Kras expression. Rutin/epigallocatechin gallate displayed the highest affinity to APC and K-RAS proteins in silico. Further research is needed to experiment on other cell lines. Results suggested that CA and PR are polyphenol-rich plant sources exhibiting antiproliferative effects in vitro.PMID:37653904 | DOI:10.3390/plants12101987

Plants (Basel). 2023 May 12;12(10):1963. doi: 10.3390/plants12101963.ABSTRACTFusarium oxysporum is the one of the most common and impactful pathogens of flax. Cultivars of flax that show resistance to this pathogen have previously been identified. To better understand the mechanisms that are responsible for this resistance, we conducted time-lapse analysis of one susceptible and one resistant cultivar over a two-week period following infection. We also monitored changes in some metabolites. The susceptible cultivar showed a strong onset of symptoms from 6 to 8 days after inoculation, which at this time point, was associated with changes in metabolites in both cultivars. The resistant cultivar maintained its height and normal photosynthetic capacity but showed a reduced growth of its secondary stems. This resistance was correlated with the containment of the pathogen at the root level, and an increase in some metabolites related to the phenylpropanoid pathway.PMID:37653880 | DOI:10.3390/plants12101963

Plants (Basel). 2023 May 10;12(10):1946. doi: 10.3390/plants12101946.ABSTRACTHere we report the medium-term effects of foliar spray and endo-therapy treatments with different doses of a Cu/Zn citric acid biocomplex (Dentamet®) in Xylella fastidiosa infected olive trees of Salento, Apulia region (South-east Italy). Leaf extract samples from field-treated 150 years old olive trees cvs Ogliarola salentina and Cellina di Nardò were studied by 1H NMR-based metabolomics. The result of different applications of Dentamet® endo-therapy after 60, 120 and 180 days in comparison with traditional foliar spray treatment and water injection as a control have been investigated. The metabolic profile analyses, performed by 1H NMR-based metabolomic approach, indicated plant metabolites variations connected to the disease progression such as mannitol, quinic acid, and oleuropein related compounds. The best results, in terms of discrimination of the metabolic profiles with respect to water injection, were found for monthly endo-therapy treatments. Dentamet® foliar application demonstrated more specific time related progressive effectiveness with respect to intravascular treatments. Therefore, besides a possible more effective performance of endo-therapy with respect to foliar treatments, the need of further doses/frequencies trimming to obtain long-term results was also assessed. The present field studies confirmed the indication of Dentamet® effectiveness in metabolic variation induction, potentially linked with reducing the X. fastidiosa subspecies pauca related Olive Quick Decline Syndrome (OQDS) symptoms development.PMID:37653863 | DOI:10.3390/plants12101946

Plants (Basel). 2023 May 9;12(10):1929. doi: 10.3390/plants12101929.ABSTRACTPhlomis purpurea grows spontaneously in the southern Iberian Peninsula, namely in cork oak (Quercus suber) forests. In a previous transcriptome analysis, we reported on its immunity against Phytophthora cinnamomi. However, little is known about the involvement of secondary metabolites in the P. purpurea defense response. It is known, though, that root exudates are toxic to this pathogen. To understand the involvement of secondary metabolites in the defense of P. purpurea, a metabolome analysis was performed using the leaves and roots of plants challenged with the pathogen for over 72 h. The putatively identified compounds were constitutively produced. Alkaloids, fatty acids, flavonoids, glucosinolates, polyketides, prenol lipids, phenylpropanoids, sterols, and terpenoids were differentially produced in these leaves and roots along the experiment timescale. It must be emphasized that the constitutive production of taurine in leaves and its increase soon after challenging suggests its role in P. purpurea immunity against the stress imposed by the oomycete. The rapid increase in secondary metabolite production by this plant species accounts for a concerted action of multiple compounds and genes on the innate protection of Phlomis purpurea against Phytophthora cinnamomi. The combination of the metabolome with the transcriptome data previously disclosed confirms the mentioned innate immunity of this plant against a devastating pathogen. It suggests its potential as an antagonist in phytopathogens' biological control. Its application in green forestry/agriculture is therefore possible.PMID:37653845 | DOI:10.3390/plants12101929

Sci Total Environ. 2023 Aug 29:166683. doi: 10.1016/j.scitotenv.2023.166683. Online ahead of print.ABSTRACTUrbanization has led to increasing use of artificial light at night (ALAN), which has rapidly become an important source of pollution in many cities. To identify the ALAN effects on the embryonic development of the Pacific abalone Haliotis discus hannai, we first exposed larvae to natural light with a light period of 12 L:12D (control, Group CTR). We then exposed larvae to three different light regimes. Larvae in Group NL were exposed to full spectrum artificial light from 18:00 to 00:00 to simulate the lighting condition at night, whereas Groups BL and YL were illuminated at the same time interval with 450 nm of short-wavelength blue light and 560 nm of long-wavelength orange light, respectively, to simulate billboard lighting at night. There were significantly higher hatching success and metamorphosis rates of larvae in Group BL than in Group YL or CTR (P < 0.05). The larvae in Group YL had the highest abnormality rate and took the longest time to complete metamorphosis. Transcriptomic studies revealed significantly higher expression levels of genes related to RNA transport, DNA replication, and protein processing in endoplasmic reticulum pathways in Group BL compared to the other groups. In the metabolomic analysis, we identified prostaglandin B1, tyramine, d-fructose 6-phosphate, L-adrenaline, leukotriene C4, and arachidonic acid as differential metabolic markers, as they play a vital part in helping larvae adapt to different ALAN conditions. Multi-omics correlation analysis of pairwise comparisons between all of the groups suggested that the biosynthesis of unsaturated fatty acids (FAs) and arachidonic acid metabolism pathways were significantly enriched (P < 0.05). Further quantitative analysis of the fatty acid (FA) contents revealed that 42 out of 50 FAs were down-regulated in Group BL and up-regulated in Group YL, which suggested that the synthesis, catabolism, and metabolism of FAs are crucial for the larval response to different spectral components of ALAN. For the first time, we report positive rather than negative effects of artificial blue light at night on the embryonic development of a benthic marine species. These results are significant for unbiased and full-scale assessment of the ecological effects of ALAN and for understanding the structural stability of the marine benthic community.PMID:37652388 | DOI:10.1016/j.scitotenv.2023.166683

J Genet Genomics. 2023 Aug 29:S1673-8527(23)00177-7. doi: 10.1016/j.jgg.2023.08.005. Online ahead of print.ABSTRACTGut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders; however, comprehensive studies on impaired glucose tolerance (IGT), a diabetes mellitus (DM) precursor, are lacking. Here, we perform metagenomic sequencing and metabolomics of 47 pairs of individuals with IGT and newly diagnosed DM, and 46 controls with normal glucose tolerance (NGT); patients with IGT are followed-up after 4 years for progression to DM. Analysis of baseline data reveal significant differences in gut microbiota and serum metabolites among the IGT, DM, and NGT groups. In addition, 13 types of gut microbiota and 17 types of circulating metabolites show significant differences at baseline before IGT progressed to DM, including higher levels of Eggerthella unclassified, Coprobacillus unclassified, Clostridium ramosum, L-valine, L-norleucine, and L-isoleucine, and lower levels of Eubacterium eligens, Bacteroides faecis, Lachnospiraceae bacterium 3_1_46FAA, Alistipes senegalensis, Megaspaera elsdenii, Clostridium perfringens, α-linolenic acid, 10E,12Z octadecadienoic acid, and dodecanoic acid. A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM (AUC = 0.87). These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.PMID:37652264 | DOI:10.1016/j.jgg.2023.08.005

Environ Pollut. 2023 Aug 29:122468. doi: 10.1016/j.envpol.2023.122468. Online ahead of print.ABSTRACTToday's women of childbearing age with a history of high lead (Pb) exposure in childhood have large Pb body burdens, which increases Pb release during pregnancy by promoting bone Pb mobilisation. The purpose of this study was to investigate the metabolic mechanisms underlying bone Pb mobilisation and explore the bone metabolism-related pathways during pregnancy. Drinking water containing 0.05% sodium acetate or Pb acetate was provided to weaned female rats for 4 weeks followed by a 4-week washout period, and then rats were co-caged with healthy males of the same age until pregnancy. Blood and bone tissues of the female rats were collected at gestational day (GD) 3 (early pregnancy), GD 10 (middle pregnancy), and GD 17 (late pregnancy), respectively. Pb and calcium concentrations, biomarkers for bone turnover, bone microstructure, serum metabolomics, and metabolic indicators were intensively analyzed. The results demonstrated that pre-pregnancy Pb exposure elevated blood lead levels (BLLs) at GD17, accompanied by a negative correlation between BLLs and trabecular bone Pb levels. Meanwhile, Pb-exposed rats had low bone mass and aberrant bone architecture with a larger number of mature osteoclasts (OCs) compared to the control group. Moreover, the metabolomics uncovered that Pb exposure caused mitochondrial dysfunction, such as enhanced oxidative stress and inflammatory response, and suppressed energy metabolism. Additionally, the levels of ROS, MDA, IL-1β, and IL-18 involved in redox and inflammatory pathways of bone tissues were significantly increased in the Pb-exposed group, while antioxidant SOD and energy metabolism-related indicators including ATP levels, Na+-K+-ATPase, and Ca2+-Mg2+-ATPase activities were significantly decreased. In conclusion, pre-pregnancy Pb exposure promotes bone Pb mobilisation and affects bone microstructure in the third trimester of pregnancy, which may be attributed to OC activation and mitochondrial dysfunction.PMID:37652228 | DOI:10.1016/j.envpol.2023.122468

J Ethnopharmacol. 2023 Aug 29:117107. doi: 10.1016/j.jep.2023.117107. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Defatted walnut powder (DWP), the byproduct remaining after extracting oil from the walnut kernel, has the actions of nourishing liver and the kidney, replenishing blood, and calming the nerves, which is believed to be a brain-nourishing in Chinese medicine. DWP is rich in phenolic substances with demonstrated anti-inflammatory, antioxidant, lipid-lowering and neuroprotective effects. Despite these promising properties of DWP, its effectiveness in treating Alzheimer's disease (AD) remains unclear, and further research is needed to understand the mechanism of action.AIM OF THE STUDY: This study aimed to investigate the potential mechanism of DWP on AD by constructing the overall metabolic profile of mice with an anti-scopolamine AD model and verification of the highly correlated pathway.MATERIALS AND METHODS: The neuroprotective efficacy of DWP in a mouse model of AD established by scopolamine injection was examined. Spatial memory performance in the Morris water maze (MWM), markers of cholinergic function in hippocampus and cortex, and neuropathological changes were compared among control, model, and DWP-consuming model group mice. In addition, combined metabolomic and proteomic analyses were conducted to investigate changes in metabolite and protein expression profiles in AD model mice induced by DWP consumption. Differentially expressed proteins and metabolites were then analyzed for KEGG pathway enrichment and results confirmed through targeted amino acid metabolomics.RESULTS: The results showed that consumption of DWP improved spatial learning and memory in the MWM, enhanced cholinergic function, and reduced histopathological damage in the cortex and hippocampus of AD model mice. Based on differentially abundant metabolites and proteins, 43 metabolic pathways modulated by DWP were identified, mainly involving in amino acid metabolic pathways strongly associated with cellular energetics and antioxidant capacity, and targeted amino acid metabolomics confirmed that DWPE significantly elevated the levels of Arginine (Arg), Histidine (His), Proline (Pro), Serine (Ser), and Tyrosine (Tyr), while reducing the levels of Glutamate (Glu). This ultimately resulted in an improvement in the progression of AD.CONCLUSION: This study identified numerous metabolic networks modulated by DWP that can mitigate scopolamine-induced AD neuropathology and cognitive dysfunction. DWP is a promising resource to identify AD-related pathogenic pathways and therapeutic strategies.PMID:37652196 | DOI:10.1016/j.jep.2023.117107

Clin Chim Acta. 2023 Aug 29:117530. doi: 10.1016/j.cca.2023.117530. Online ahead of print.ABSTRACTBACKGROUND: Asthenozoospermia (AZS) is a disease characterized by decreased sperm motility induced by multiple etiologies, and the pathological mechanisms of various AZS are unclear. We simultaneously analyzed the metabolic profiling of four representative AZS to provide new insights into the etiologies of AZS.METHOD: Seminal plasma samples were collected from healthy control (HC; n=30) and four AZS induced by varicocele (VA, n=30), obesity (OA, n=22), reproductive system infections (RA; n=17) and idiopathic (IA, n=30), respectively, and were analyzed using gas chromatography-mass spectrometry. Disturbed metabolites and metabolic pathways were compared between AZS and HC, as well as IA and the other three AZS.RESULTS: A total of 40 different metabolites were identified in the seminal plasma of AZS and HC, of which lactic acid, fructose, citric acid, glutamine and pyruvic acid metabolic abnormalities associated with all the AZS groups, while each AZS group had unique metabolic changes. RA was significantly separated from the other three AZS, and metabolites such as cholesterol, octadecanoic acid and serine mainly contributed to the separation.CONCLUSION: The comprehensive metabolomic analysis and comparison of four various AZS provided evidence and clues for the mechanism mining, which will benefit future etiology, diagnosis and treatment of AZS.PMID:37652159 | DOI:10.1016/j.cca.2023.117530

Curr Opin Plant Biol. 2023 Aug 29;75:102437. doi: 10.1016/j.pbi.2023.102437. Online ahead of print.NO ABSTRACTPMID:37651960 | DOI:10.1016/j.pbi.2023.102437

Plant Physiol Biochem. 2023 Aug 25;202:107986. doi: 10.1016/j.plaphy.2023.107986. Online ahead of print.ABSTRACTTo gain insights into the adaptive characteristics of ephemeral plants and enrich their potential for resource exploitation, the adaptive changes in two highly dominant species (Malcolmia scorpioides and Isatis violascens) to soil habitats (aeolian soil, AS; grey desert soil, GS) were investigated from the aspects of root morphology, physiology, and metabolism in this study. The results revealed that changes in root morphology and enzyme activity were affected by soil habitat. Total root length (TRL), root volume (RV) and root surface area (RSA) were higher in GS than in AS. The levels of proline (Pro), glutathione (GSH), soluble sugar (SS), and lysine (Lys) were higher in GS than in AS. Untargeted LC-MS metabolomics indicates that root metabolites of both species differed among the two soil habitats. Root responses to different soil habitats mainly affected some metabolic pathways. A total of 780 metabolites were identified, common differential metabolites (DMs) in both species included amino acids, fatty acids, organic acids, carbohydrates, benzene and derivatives, and flavonoids, which were mainly involved in carbohydrate metabolism, amino acid metabolism, flavonoid biosynthesis and fatty acid metabolism, and their abundance varied among different habitats and species. Some key DMs were significantly related to root morphology and enzyme activity, and indole, malonate, quercetin, uridine, tetrahydroharmine, and gluconolactone were important metabolites associated with root growth. Therefore, the response changes in root growth and metabolite of ephemeral plants in response to soil habitats reflect their ecological adaptation, and lay a foundation for the exploitation of plant resources in various habitats.PMID:37651954 | DOI:10.1016/j.plaphy.2023.107986

Biosens Bioelectron. 2023 Aug 25;240:115635. doi: 10.1016/j.bios.2023.115635. Online ahead of print.ABSTRACTHuman cerebral organoids (COs), generated from stem cells, are emerging animal alternatives for understanding brain development and neurodegeneration diseases. Long-term growth of COs is currently hindered by the limitation of efficient oxygen infiltration and continuous nutrient supply, leading to general inner hypoxia and cell death at the core region of the organoids. Here, we developed a three-dimensional (3D) microfluidic platform with dynamic fluidic perturbation and oxygen supply. We demonstrated COs cultured in the 3D microfluidic system grew continuously for over 50 days without cell death at the core region. Increased cell proliferation and enhanced cell differentiation were also observed and verified with immunofluorescence staining, proteomics and metabolomics. Time-lapse proteomics from 7 consecutive acquisitions between day 4 and day 30 identified 546 proteins differently expressed accompanying COs growth, which were mainly relevant to nervous system development, in utero embryonic development, brain development and neuron migration. Our 3D microfluidic platform provides potential utility for culturing high-homogeneous human organoids.PMID:37651948 | DOI:10.1016/j.bios.2023.115635

J Pharm Biomed Anal. 2023 Aug 21;236:115677. doi: 10.1016/j.jpba.2023.115677. Online ahead of print.ABSTRACTBronchoalveolar lavage (BAL) has been widely applied for the diagnosis of pulmonary diseases in clinical as it was recognized as a minimally invasive, well-tolerated and easily performed procedure. Lipid analysis of BAL fluid is a comprehensive strategy to observe lipid phenotypes, explore potential biomarkers, and elucidate the biological mechanisms of respiratory diseases. However, the highly diverse concentration of lipids in BAL fluid due to the deviation between the retrieved and injected aliquot volumes during lavage raised a challenge in obtaining high-quality lipidomic data. Here, this study aims to investigate what volume of BAL fluid is suitable for lipidomic analysis. Specifically, the BAL fluid harvested from H1N1 infected mice and controls was concentrated to varying degrees by freeze-drying technique before preparation for lipidomic analysis. The optimal concentration multiple of BAL fluid was approved by comparing the coverage and quality of identified lipids, as well as the number of differentially expressed lipids in the H1N1 infection model. Sixty-two differential lipids were identified respectively in the positive and negative modes when the BAL fluid was condensed five times, and they were classified into glycerolipids, phospholipids and fatty acids. This study focuses on the alterations of phospholipids, since they are the main constituents of pulmonary surfactants. Several phospholipids significantly accumulated in the BAL fluid of H1N1-infected mice, while most of them contained omega-3 polyunsaturated fatty acids, indicating disrupted inflammatory homeostasis in lungs. This study recommends freeze-drying/reconstitution prior to lipid extraction from BAL fluid for lipidomic analysis, as this procedure increased the richness and abundance of lipids.PMID:37651923 | DOI:10.1016/j.jpba.2023.115677

Ecotoxicol Environ Saf. 2023 Aug 29;264:115392. doi: 10.1016/j.ecoenv.2023.115392. Online ahead of print.ABSTRACTAdverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry. The critical issue that needs to be solved urgently is to evaluate the safety of traditional Chinese medicine systematically and effectively. Podophyllotoxin (PPT) is a highly active compound extracted from plants of the genus Podophyllum such as Dysosma versipellis (DV). However, its high toxicity and toxicity to multiple target organs affect the clinical application, such as the liver and kidney. Based on the concurrent effects of PPT's medicinal activity and toxicity, it would be a good example to conduct a systematic review of its safety. Therefore, this study revolves around the Toxicological Evidence Chain (TEC) concept. Based on PPT as the main toxic constituent in DV, observe the objective toxicity impairment phenotype of animals. Evaluate the serum biochemical indicators and pathological tissue sections for substantial toxic damage results. Using metabolomics, lipidomics, and network toxicology to evaluate the nephrotoxicity of PPT from multiple perspectives systematically. The results showed that PPT-induced nephrotoxicity manifested as renal tubular damage, mainly affecting metabolic pathways such as glycerophospholipid metabolism and sphingolipid metabolism. PPT inhibits the autophagy process of kidney cells through the PI3K/Akt/mTOR and Nrf2/HO1 pathways and induces the activation of oxidative stress in the body, thereby causing nephrotoxic injury. This study fully verified the feasibility of the TEC concept for the safety and toxicity evaluation of traditional Chinese medicine. Provide a research template for systematically evaluating the safety of traditional Chinese medicine.PMID:37651795 | DOI:10.1016/j.ecoenv.2023.115392

Ecotoxicol Environ Saf. 2023 Aug 29;264:115418. doi: 10.1016/j.ecoenv.2023.115418. Online ahead of print.ABSTRACTAs a heavy metal, copper is toxic to aquatic organisms in water, causing oxidative stress and lipid deposition. However, there is currently no effective dietary strategy to prevent damage caused by copper exposure. Here, copper bioaccumulation, antioxidant enzymes, lipogenic enzymes, lipid metabolism-related gene expression levels and metabolic pathways were synthesized and evaluated in copper-exposed largemouth bass (Micropterus salmoides) after hydrolysis fish peptides (HFP) pretreatment. The results showed that supplementation with 1% (P < 0.05), 3% (P < 0.01) and 5% (P < 0.05) HFP significantly reduced the copper bioaccumulation in largemouth bass. Hydrolysis fish peptides supplementation significantly reduced the activities of total antioxidant capacity (P < 0.01) and catalase (P < 0.01) and the contents of glutathione (P < 0.01) and malondialdehyde (P < 0.05). Fatty acid synthetase concentration was significantly reduced in fish supplemented with 3% (P < 0.05) and 5% HFP (P < 0.05). Similarly, fish fed 3% (P < 0.05) and 5% (P < 0.01) HFP significantly reduced the glucose-6-phosphate dehydrogenase concentration. Serum metabolomics revealed that 85, 144 and 207 differential metabolites were obtained in fish supplemented with 1%, 3% and 5% HFP, respectively. The differential metabolites were mainly lipids and lipid-like molecules, which were associated with the lipid metabolism pathways. The expression levels of fatty acid synthase (P < 0.01), sterol regulatory element binding protein-1c (P < 0.05), liver X receptor (P < 0.001), peroxisome proliferator activated γ (P < 0.01), apolipoprotein B (P < 0.001) and fatty acid-binding protein 1 (P < 0.01) were significantly down-regulated and the expression levels of carnitine palmitoyltransferase 1α (P < 0.01), hormone-sensitive lipase (P < 0.001), apolipoprotein A 1 (P < 0.05) were significantly up-regulated in fish fed with 3% HFP. Additionally, supplementation with 3% (P < 0.01) and 5% (P < 0.001) HFP significantly up-regulated the expression level of B-cell lymphoma-2 with a dose-dependent effect. In conclusion, our study confirmed that HFP supplementation was closely associated with oxidative stress, enzymatic activities and related pathways of lipid metabolism, and apoptosis, and in general alleviated lipid deposition caused by copper exposure in largemouth bass.PMID:37651792 | DOI:10.1016/j.ecoenv.2023.115418

Cancer Metab. 2023 Aug 31;11(1):13. doi: 10.1186/s40170-023-00316-0.ABSTRACTBACKGROUND: Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there. As with most viral cancers, infection with KSHV alone is insufficient to induce tumorigenesis. Indeed, KSHV infection of primary human endothelial cell cultures, even at high levels, is rarely associated with long-term culture, transformation, or growth deregulation, yet infection in vivo is sustained for life. Investigations of immune mediators that distinguish KSHV infection, KSHV/HIV co-infection, and symptomatic KS disease have yet to reveal consistent correlates of protection against or progression to KS. In addition to viral infection, it is plausible that pathogenesis also requires an immunological and metabolic environment permissive to the abnormal endothelial cell growth evident in KS tumors. In this study, we explored whether plasma metabolomes could differentiate asymptomatic KSHV-infected individuals with or without HIV co-infection and symptomatic KS from each other.METHODS: To investigate how metabolic changes may correlate with co-infections and tumorigenesis, plasma samples derived from KSHV seropositive sub-Saharan African subjects in three groups, (A) asymptomatic (lacking neoplastic disease) with KSHV infection only, (B) asymptomatic co-infected with KSHV and HIV, and (C) symptomatic with clinically diagnosed KS, were subjected to analysis of lipid and polar metabolite profiles RESULTS: Polar and nonpolar plasma metabolic differentials were evident in both comparisons. Integration of the metabolic findings with our previously reported KS transcriptomics data suggests dysregulation of amino acid/urea cycle and purine metabolic pathways, in concert with viral infection in KS disease progression.CONCLUSIONS: This study is, to our knowledge, the first to report human plasma metabolic differentials between in vivo KSHV infection and co-infection with HIV, as well as differentials between co-infection and epidemic KS.PMID:37653396 | DOI:10.1186/s40170-023-00316-0

Commun Biol. 2023 Aug 31;6(1):896. doi: 10.1038/s42003-023-05230-1.ABSTRACTThe dominant benthic primary producers in coral reef ecosystems are complex holobionts with diverse microbiomes and metabolomes. In this study, we characterize the tissue metabolomes and microbiomes of corals, macroalgae, and crustose coralline algae via an intensive, replicated synoptic survey of a single coral reef system (Waimea Bay, O'ahu, Hawaii) and use these results to define associations between microbial taxa and metabolites specific to different hosts. Our results quantify and constrain the degree of host specificity of tissue metabolomes and microbiomes at both phylum and genus level. Both microbiome and metabolomes were distinct between calcifiers (corals and CCA) and erect macroalgae. Moreover, our multi-omics investigations highlight common lipid-based immune response pathways across host organisms. In addition, we observed strong covariation among several specific microbial taxa and metabolite classes, suggesting new metabolic roles of symbiosis to further explore.PMID:37653089 | DOI:10.1038/s42003-023-05230-1

Commun Biol. 2023 Aug 31;6(1):893. doi: 10.1038/s42003-023-05266-3.ABSTRACTThis study provides a thorough comparison of the plasma metabolome of two rabbit lines divergently selected for intramuscular fat content (IMF). The divergent selection led to a correlated response in the overall adiposity, turning these lines into a valuable animal material to study also the genetics of obesity. Over 900 metabolites were detected, and the adjustment of multivariate models, both discriminant and linear, allowed to identify 322 with differential abundances between lines, which also adjusted linearly to the IMF content. The most affected pathways were those of lipids and amino acids, with differences between lines ranging from 0.23 to 6.04 standard deviations, revealing a limited capacity of the low-IMF line to obtain energy from lipids, and a greater branched-chain amino acids catabolism in the high-IMF line related to its increased IMF content. Additionally, changes in metabolites derived from microbial activity supported its relevant role in the lipid deposition. Future research will focus on the analysis of the metabolomic profile of the cecum content, and on the integration of the several -omics datasets available for these lines, to help disentangle the host and microbiome biological mechanisms involved in the IMF deposition.PMID:37653068 | DOI:10.1038/s42003-023-05266-3

Nat Metab. 2023 Aug 31. doi: 10.1038/s42255-023-00879-8. Online ahead of print.ABSTRACTIn the tumor microenvironment, adipocytes function as an alternate fuel source for cancer cells. However, whether adipocytes influence macromolecular biosynthesis in cancer cells is unknown. Here we systematically characterized the bidirectional interaction between primary human adipocytes and ovarian cancer (OvCa) cells using multi-platform metabolomics, imaging mass spectrometry, isotope tracing and gene expression analysis. We report that, in OvCa cells co-cultured with adipocytes and in metastatic tumors, a part of the glucose from glycolysis is utilized for the biosynthesis of glycerol-3-phosphate (G3P). Normoxic HIF1α protein regulates the altered flow of glucose-derived carbons in cancer cells, resulting in increased glycerophospholipids and triacylglycerol synthesis. The knockdown of HIF1α or G3P acyltransferase 3 (a regulatory enzyme of glycerophospholipid synthesis) reduced metastasis in xenograft models of OvCa. In summary, we show that, in an adipose-rich tumor microenvironment, cancer cells generate G3P as a precursor for critical membrane and signaling components, thereby promoting metastasis. Targeting biosynthetic processes specific to adipose-rich tumor microenvironments might be an effective strategy against metastasis.PMID:37653041 | DOI:10.1038/s42255-023-00879-8

Signal Transduct Target Ther. 2023 Sep 1;8(1):326. doi: 10.1038/s41392-023-01515-3.ABSTRACTWhether the alternated microbiota in the gut contribute to the risk of allograft rejection (AR) and pulmonary infection (PI) in the setting of lung transplant recipients (LTRs) remains unexplored. A prospective multicenter cohort of LTRs was identified in the four lung transplant centers. Paired fecal and serum specimens were collected and divided into AR, PI, and event-free (EF) groups according to the diagnosis at sampling. Fecal samples were determined by metagenomic sequencing. And metabolites and cytokines were detected in the paired serum to analyze the potential effect of the altered microbiota community. In total, we analyzed 146 paired samples (AR = 25, PI = 43, and EF = 78). Notably, we found that the gut microbiome of AR followed a major depletion pattern with decreased 487 species and compositional diversity. Further multi-omics analysis showed depleted serum metabolites and increased inflammatory cytokines in AR and PI. Bacteroides uniformis, which declined in AR (2.4% vs 0.6%) and was negatively associated with serum IL-1β and IL-12, was identified as a driven specie in the network of gut microbiome of EF. Functionally, the EF specimens were abundant in probiotics related to mannose and cationic antimicrobial peptide metabolism. Furthermore, a support-vector machine classifier based on microbiome, metabolome, and clinical parameters highly predicted AR (AUPRC = 0.801) and PI (AUPRC = 0.855), whereby the microbiome dataset showed a particularly high diagnostic power. In conclusion, a disruptive gut microbiota showed a significant association with allograft rejection and infection and with systemic cytokines and metabolites in LTRs.PMID:37652953 | DOI:10.1038/s41392-023-01515-3