PubMed

Nucleic Acids Res. 2023 Oct 23:gkad880. doi: 10.1093/nar/gkad880. Online ahead of print.ABSTRACTDiverse individuals age at different rates and display variable susceptibilities to tissue aging, functional decline and aging-related diseases. Centenarians, exemplifying extreme longevity, serve as models for healthy aging. The field of human aging and longevity research is rapidly advancing, garnering significant attention and accumulating substantial data in recent years. Omics technologies, encompassing phenomics, genomics, transcriptomics, proteomics, metabolomics and microbiomics, have provided multidimensional insights and revolutionized cohort-based investigations into human aging and longevity. Accumulated data, covering diverse cells, tissues and cohorts across the lifespan necessitates the establishment of an open and integrated database. Addressing this, we established the Human Aging and Longevity Landscape (HALL), a comprehensive multi-omics repository encompassing a diverse spectrum of human cohorts, spanning from young adults to centenarians. The core objective of HALL is to foster healthy aging by offering an extensive repository of information on biomarkers that gauge the trajectory of human aging. Moreover, the database facilitates the development of diagnostic tools for aging-related conditions and empowers targeted interventions to enhance longevity. HALL is publicly available at https://ngdc.cncb.ac.cn/hall/index.PMID:37870433 | DOI:10.1093/nar/gkad880

J Vis Exp. 2023 Oct 6;(200). doi: 10.3791/66012.ABSTRACTBrown adipose tissue (BAT) plays a crucial role in regulating metabolic homeostasis through a unique energy expenditure process known as non-shivering thermogenesis. To achieve this, BAT utilizes a diverse menu of circulating nutrients to support its high metabolic demand. Additionally, BAT secretes metabolite-derived bioactive factors that can serve as either metabolic fuels or signaling molecules, facilitating BAT-mediated intratissue and/or intertissue communication. This suggests that BAT actively participates in systemic metabolite exchange, an interesting feature that is beginning to be explored. Here, we introduce a protocol for in vivo mouse-level optimized BAT arteriovenous metabolomics. The protocol focuses on relevant methods for thermogenic stimulations and an arteriovenous blood sampling technique using Sulzer's vein, which selectively drains interscapular BAT-derived venous blood and systemic arterial blood. Next, a gas chromatography-based metabolomics protocol using those blood samples is demonstrated. The use of this technique should expand the understanding of BAT-regulated metabolite exchange at the inter-organ level by measuring the net uptake and release of metabolites by BAT.PMID:37870308 | DOI:10.3791/66012

J Agric Food Chem. 2023 Oct 23. doi: 10.1021/acs.jafc.3c05117. Online ahead of print.ABSTRACTSafflower (Carthamus tinctorius L.) is a multipurpose economic crop that is distributed worldwide. Flavonoid glycosides are the main bioactive components in safflower, but only a few UDP-glycosyltransferases (UGT) have been identified. Three differentially expressed UGT genes related with the accumulation of 9 flavonoid O-glycosides were screened from metabolomics and transcriptome analysis. Safflower corolla protoplasts were used to confirm the glycosylation ability of UGT candidates in vivo for the first time. The astragalin content was significantly increased only when CtUGT3 was overexpressed. CtUGT3 also showed flavonoid 3-OH and 7-OH glycosylation activities in vitro. Molecular modeling and site-directed mutagenesis revealed that G15, T136, S276, and E384 were critical catalytic residues for the glycosylation ability of CtUGT3. These results demonstrate that CtUGT3 has a flavonoid 3-OH glycosylation function and is involved in the biosynthesis of astragalin in safflower. This study provides a reference for flavonoid biosynthesis genes research in nonmodel plants.PMID:37870279 | DOI:10.1021/acs.jafc.3c05117

Ann Surg. 2023 Oct 23. doi: 10.1097/SLA.0000000000006137. Online ahead of print.ABSTRACTOBJECTIVE: To investigate if ischemia alters donor kidney metabolism and whether these changes associate with organ function.SUMMARY BACKGROUND DATA: An unmet need in kidney transplantation is the ability to predict post-transplant organ function before transplantation. Key to such viability testing is a profound understanding of the organ's complex biochemistry and how ischemia, inevitable during the transplantation process, influences this.METHODS: First, metabolic changes in glucose, lactate and 20 amino acids induced by no, 1h of warm, or 22h of cold ischemia were investigated during 4h perfusion of pig kidneys with autologous whole blood (n=6/group), simulating the ischemia-reperfusion phase of transplantation. Next, we confirmed similar metabolic changes during normothermic preservation of pig (n=3/group; n=4 for cold ischemia) and discarded human kidneys (n=6) perfused with a red-blood cell based perfusate.RESULTS: At 2h of perfusion with autologous whole blood, abundances of 17/20 amino acids were significantly different between groups, reflecting the type of ischemia. Amino acid changes at 15 min and 2h of perfusion correlated with future kidney function during perfusion. Similar metabolic patterns were observed during perfusion preservation of pig and discarded human donor kidneys, suggesting an opportunity to assess kidney viability before transplantation.CONCLUSIONS: Perfusate metabolite changes during normothermic kidney perfusion represent a unique non-invasive opportunity to assess graft viability. These findings now need validation in transplant studies.PMID:37870241 | DOI:10.1097/SLA.0000000000006137

Vet Q. 2023 Oct 23:1-17. doi: 10.1080/01652176.2023.2273891. Online ahead of print.ABSTRACTHigh-protein diets may aid weight loss and weight maintenance programs in both humans and dogs, although the effect of dietary protein levels on gut metabolism and functionality has not been studied in depth. The current study aimed to investigate the effect of an altered dietary protein:carbohydrate ratio on gut function in adult dogs by means of faecal metabolomic fingerprinting. More specifically, functional metabolic differences in dogs fed a high-protein/low-carbohydrate (HPLC) vs. low-protein/high-carbohydrate (LPHC) diet were studied by equally allocating twelve clinically healthy (6 lean and 6 obese) Beagles into two groups in a cross-over design, with each group receiving two isocaloric diets for four weeks. The faecal metabolome revealed that different protein:carbohydrate ratio can influence host and/or gut microbiome metabolism and function, while no effect was observed on the body condition. Targeted analysis demonstrated that the HPLC diet significantly increased the concentration of indole, spermidine and pipecolinic acid and decreased the concentration of azelaic acid, D-fructose, mannose, and galactose (P < 0.05). Multivariate modelling (OPLS-DA) of the untargeted faecal metabolome revealed distinctly different metabolomic profiles following the HPLC vs. LPHC diet, with 18 altered pathways. The HPLC diet influenced amino acid and lipid metabolism, potentially promoting weight loss and immune function, whereas the LPHC diet affected carbohydrate fermentation and may promote anti-oxidative function.PMID:37869782 | DOI:10.1080/01652176.2023.2273891

Front Physiol. 2023 Oct 6;14:1273342. doi: 10.3389/fphys.2023.1273342. eCollection 2023.ABSTRACTThis study aims to explore the molecular regulatory mechanisms of acute exercise in the skeletal muscle of mice. Male C57BL/6 mice were randomly assigned to the control group, and the exercise group, which were sacrificed immediately after an acute bout of exercise. The study was conducted to investigate the metabolic and transcriptional profiling in the quadriceps muscles of mice. The results demonstrated the identification of 34 differentially expressed metabolites (DEMs), with 28 upregulated and 6 downregulated, between the two groups. Metabolic pathway analysis revealed that these DEMs were primarily enriched in several, including the citrate cycle, propanoate metabolism, and lysine degradation pathways. In addition, the results showed a total of 245 differentially expressed genes (DEGs), with 155 genes upregulated and 90 genes downregulated. KEGG analysis indicated that these DEGs were mainly enriched in various pathways such as ubiquitin mediated proteolysis and FoxO signaling pathway. Furthermore, the analysis revealed significant enrichment of DEMs and DEGs in signaling pathways such as protein digestion and absorption, ferroptosis signaling pathway. In summary, the identified multiple metabolic pathways and signaling pathways were involved in the exercise-induced physiological regulation of skeletal muscle, such as the TCA cycle, oxidative phosphorylation, protein digestion and absorption, the FoxO signaling pathway, ubiquitin mediated proteolysis, ferroptosis signaling pathway, and the upregulation of KLF-15, FoxO1, MAFbx, and MuRF1 expression could play a critical role in enhancing skeletal muscle proteolysis.PMID:37869715 | PMC:PMC10587468 | DOI:10.3389/fphys.2023.1273342

Exp Ther Med. 2023 Sep 28;26(5):533. doi: 10.3892/etm.2023.12232. eCollection 2023 Nov.ABSTRACTExposure to hypoxia disrupts energy metabolism and induces inflammation. However, the pathways and mechanisms underlying energy metabolism disorders caused by hypoxic conditions remain unclear. In the present study, a hypoxic animal model was created and transcriptomic and non-targeted metabolomics techniques were applied to further investigate the pathways and mechanisms of hypoxia exposure that disrupt energy metabolism. Transcriptome results showed that 3,007 genes were significantly differentially expressed under hypoxic exposure, and Gene Ontology annotation analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis showed that the differentially expressed genes (DEGs) were mainly involved in energy metabolism and were significantly enriched in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) pathway. The DEGs IDH3A, SUCLA2, and MDH2 in the TCA cycle and the DEGs NDUFA3, NDUFS7, UQCRC1, CYC1 and UQCRFS1 in the OXPHOS pathway were validated using mRNA and protein expression, and the results showed downregulation. The results of non-targeted metabolomics showed that 365 significant differential metabolites were identified under plateau hypoxia stress. KEGG enrichment analysis showed that the differential metabolites were mainly enriched in metabolic processes, such as energy, nucleotide and amino acid metabolism. Hypoxia exposure disrupted the TCA cycle and reduced the synthesis of amino acids and nucleotides by decreasing the concentration of cis-aconitate, α-ketoglutarate, NADH, NADPH and that of most amino acids, purines, and pyrimidines. Bioinformatics analysis was used to identify inflammatory genes related to hypoxia exposure and some of them were selected for verification. It was shown that the mRNA and protein expression levels of IL1B, IL12B, S100A8 and S100A9 in kidney tissues were upregulated under hypoxic exposure. The results suggest that hypoxia exposure inhibits the TCA cycle and the OXPHOS signalling pathway by inhibiting IDH3A, SUCLA2, MDH2, NDUFFA3, NDUFS7, UQCRC1, CYC1 and UQCRFS1, thereby suppressing energy metabolism, inducing amino acid and nucleotide deficiency and promoting inflammation, ultimately leading to kidney damage.PMID:37869643 | PMC:PMC10587886 | DOI:10.3892/etm.2023.12232

RSC Adv. 2023 Oct 19;13(44):30665-30679. doi: 10.1039/d3ra04037b. eCollection 2023 Oct 18.ABSTRACTMetabolomics and molecular networking approaches have expanded rapidly in the field of biological sciences and involve the systematic identification, visualization, and high-throughput characterization of bioactive metabolites in natural products using sophisticated mass spectrometry-based techniques. The popularity of natural products in pharmaceutical therapies has been influenced by medicinal plants with a long history of ethnobotany and a vast collection of bioactive compounds. Here, we selected four medicinal plants Cleistocalyx operculatus, Terminalia chebula, Ficus lacor, and Ficus semicordata, the biochemical characteristics of which remain unclear owing to the inherent complexity of their plant metabolites. In this study, we aimed to evaluate the potential of these aforementioned plant extracts in inhibiting the enzymatic activity of α-amylase and α-glucosidase, respectively, followed by the annotation of secondary metabolites. The methanol extract of Ficus semicordata exhibited the highest α-amylase inhibition with an IC50 of 46.8 ± 1.8 μg mL-1, whereas the water fraction of Terminalia chebula fruits demonstrated the most significant α-glucosidase inhibition with an IC50 value of 1.07 ± 0.01 μg mL-1. The metabolic profiling of plant extracts was analyzed through Liquid Chromatography-Mass Spectrometry (LC-HRMS) of the active fractions, resulting in the annotation of 32 secondary metabolites. Furthermore, we applied the Global Natural Product Social Molecular Networking (GNPS) platform to evaluate the MS/MS data of Terminalia chebula (bark), revealing that there were 205 and 160 individual ion species observed as nodes in the methanol and ethyl acetate fractions, respectively. Twenty-two metabolites were tentatively identified from the network map, of which 11 compounds were unidentified during manual annotation.PMID:37869390 | PMC:PMC10585453 | DOI:10.1039/d3ra04037b

Front Aging Neurosci. 2023 Oct 6;15:1211979. doi: 10.3389/fnagi.2023.1211979. eCollection 2023.ABSTRACTA key role of the gut microbiota in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), has been identified over the past decades. Increasing clinical and preclinical evidence implicates that there is bidirectional communication between the gut microbiota and the central nervous system (CNS), which is also known as the microbiota-gut-brain axis. Nevertheless, current knowledge on the interplay between gut microbiota and the brain remains largely unclear. One of the primary mediating factors by which the gut microbiota interacts with the host is peripheral metabolites, including blood or gut-derived metabolites. However, mechanistic knowledge about the effect of the microbiome and metabolome signaling on the brain is limited. Neuroimaging techniques, such as multi-modal magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (FDG-PET), have the potential to directly elucidate brain structural and functional changes corresponding with alterations of the gut microbiota and peripheral metabolites in vivo. Employing a combination of gut microbiota, metabolome, and advanced neuroimaging techniques provides a future perspective in illustrating the microbiota-gut-brain pathway and further unveiling potential therapeutic targets for AD treatments.PMID:37869373 | PMC:PMC10587434 | DOI:10.3389/fnagi.2023.1211979

Ophthalmol Sci. 2023 Jul 1;4(1):100357. doi: 10.1016/j.xops.2023.100357. eCollection 2024 Jan-Feb.ABSTRACTPURPOSE: The most widely used classifications of age-related macular degeneration (AMD) and its severity stages still rely on color fundus photographs (CFPs). However, AMD has a wide phenotypic variability that remains poorly understood and is better characterized by OCT. We and others have shown that patients with AMD have a distinct plasma metabolomic profile compared with controls. However, all studies to date have been performed solely based on CFP classifications. This study aimed to assess if plasma metabolomic profiles are associated with OCT features commonly seen in AMD.DESIGN: Prospectively designed, cross-sectional study.PARTICIPANTS: Subjects with a diagnosis of AMD and a control group (> 50 years old) from Boston, United States, and Coimbra, Portugal.METHODS: All participants were imaged with CFP, used for AMD staging (Age-Related Eye Disease Study 2 classification scheme), and with spectral domain OCT (Spectralis, Heidelberg). OCT images were graded by 2 independent graders for the presence of characteristic AMD features, according to a predefined protocol. Fasting blood samples were collected for metabolomic profiling (using nontargeted high-resolution mass spectrometry by Metabolon Inc). Analyses were conducted using logistic regression models including the worst eye of each patient (AREDS2 classification) and adjusting for confounding factors. Each cohort (United States and Portugal) was analyzed separately and then results were combined by meta-analyses. False discovery rate (FDR) was used to account for multiple comparisons.MAIN OUTCOME MEASURES: Plasma metabolite levels associated with OCT features.RESULTS: We included data on 468 patients, 374 with AMD and 94 controls, and on 725 named endogenous metabolites. Meta-analysis identified significant associations (FDR < 0.05) between plasma metabolites and 3 OCT features: hyperreflective foci (6), atrophy (6), and ellipsoid zone disruption (3). Most associations were seen with amino acids, and all but 1 metabolite presented specific associations with the OCT features assessed.CONCLUSIONS: To our knowledge, we show for the first time that plasma metabolites have associations with specific OCT features seen in AMD. Our results support that the wide spectrum of presentations of AMD likely include different pathophysiologic mechanisms by identifying specific pathways associated with each OCT feature.FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.PMID:37869026 | PMC:PMC10587636 | DOI:10.1016/j.xops.2023.100357

Front Immunol. 2023 Oct 5;14:1225603. doi: 10.3389/fimmu.2023.1225603. eCollection 2023.ABSTRACTFetal and neonatal alloimmune thrombocytopenia (FNAIT) can occur due to maternal IgG antibodies targeting platelet antigens, causing life-threatening bleeding in the neonate. However, the disease manifests itself in only a fraction of pregnancies, most commonly with anti-HPA-1a antibodies. We found that in particular, the core fucosylation in the IgG-Fc tail is highly variable in anti-HPA-1a IgG, which strongly influences the binding to leukocyte IgG-Fc receptors IIIa/b (FcγRIIIa/b). Currently, gold-standard IgG-glycoanalytics rely on complicated methods (e.g., mass spectrometry (MS)) that are not suited for diagnostic purposes. Our aim was to provide a simplified method to quantify the biological activity of IgG antibodies targeting cells. We developed a cellular surface plasmon resonance imaging (cSPRi) technique based on FcγRIII-binding to IgG-opsonized cells and compared the results with MS. The strength of platelet binding to FcγR was monitored under flow using both WT FcγRIIIa (sensitive to Fc glycosylation status) and mutant FcγRIIIa-N162A (insensitive to Fc glycosylation status). The quality of the anti-HPA-1a glycosylation was monitored as the ratio of binding signals from the WT versus FcγRIIIa-N162A, using glycoengineered recombinant anti-platelet HPA-1a as a standard. The method was validated with 143 plasma samples with anti-HPA-1a antibodies analyzed by MS with known clinical outcomes and tested for validation of the method. The ratio of patient signal from the WT versus FcγRIIIa-N162A correlated with the fucosylation of the HPA-1a antibodies measured by MS (r=-0.52). Significantly, FNAIT disease severity based on Buchanan bleeding score was similarly discriminated against by MS and cSPRi. In conclusion, the use of IgG receptors, in this case, FcγRIIIa, on SPR chips can yield quantitative and qualitative information on platelet-bound anti-HPA-1a antibodies. Using opsonized cells in this manner circumvents the need for purification of specific antibodies and laborious MS analysis to obtain qualitative antibody traits such as IgG fucosylation, for which no clinical test is currently available.PMID:37868955 | PMC:PMC10585714 | DOI:10.3389/fimmu.2023.1225603

Front Cell Infect Microbiol. 2023 Sep 12;13:1254016. doi: 10.3389/fcimb.2023.1254016. eCollection 2023.ABSTRACTBACKGROUND: Clonorchiasis is an important foodborne parasitic disease. However, eggs of Clonorchis sinensis (C. sinensis) cannot be detected in feces during biliary obstruction. Moreover, many diseases can cause biliary obstruction, such as gallstones, adenocarcinoma, cholangiocarcinoma and Ascaris lumbricoides infection. Therefore, it is of great significance to distinguish between patients of biliary obstruction and biliary obstruction with C. sinensis infection.METHODS: A total of 48 biliary obstruction patients were enrolled, including 23 infected with C. sinensis (C. sinensis) (OB+C.s) and 25 non-infected subjects (OB). The bile samples were collected by endoscopic retrograde cholangiopancreatography and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). Additionally, multivariate statistical analysis methods were employed to identify differential metabolites. Next, bile amino acid levels were determined by targeted metabolomics analysis.RESULT: A total of 146 and 132 significant metabolites were identified in electrospray ionization (ESI)+ and ESI- modes, respectively. The levels of amino acids (asparagine, glutamate, ornithine) and polyamines (spermidine and spermine) were significantly changed. Targeted analysis showed that the levels of amino acids (such as L-arginine, L-glutamine, L-lysine, L-propionic, and L-tyrosine) were lower in OB+C.s patients compared to those in OB patients. Marked metabolic pathways were involved in "Glutathione metabolism", "Caffeine metabolism", "Alanine, aspartate and glutamate metabolism", "Arginine and proline metabolism", "Purine metabolism", "Beta-Alanine metabolism", and "D-glutamine and D-glutamate metabolism".CONCLUSION: These results show that there were significant differences between OB+C.s and OB patients, especially in amino acids. The metabolic signature and perturbations in metabolic pathways may help to better distinguish OB+C.s and OB patients.PMID:37868349 | PMC:PMC10585366 | DOI:10.3389/fcimb.2023.1254016

Front Plant Sci. 2023 Oct 5;14:1216702. doi: 10.3389/fpls.2023.1216702. eCollection 2023.ABSTRACTBACKGROUND: Nicotiana tabacum is an important economic crop, which is widely planted in the world. Lignin is very important for maintaining the physiological and stress-resistant functions of tobacco. However, higher lignin content will produce lignin gas, which is not conducive to the formation of tobacco quality. To date, how to precisely fine-tune lignin content or composition remains unclear.RESULTS: Here, we annotated and screened 14 CCoAOMTs in Nicotiana tabacum and obtained homozygous double mutants of CCoAOMT6 and CCoAOMT6L through CRSIPR/Cas9 technology. The phenotype showed that the double mutants have better growth than the wild type whereas the S/G ratio increased and the total sugar decreased. Resistance against the pathogen test and the extract inhibition test showed that the transgenic tobacco has stronger resistance to tobacco bacterial wilt and brown spot disease, which are infected by Ralstonia solanacearum and Alternaria alternata, respectively. The combined analysis of metabolome and transcriptome in the leaves and roots suggested that the changes of phenylpropane and terpene metabolism are mainly responsible for these phenotypes. Furthermore, the molecular docking indicated that the upregulated metabolites, such as soyasaponin Bb, improve the disease resistance due to highly stable binding with tyrosyl-tRNA synthetase targets in Ralstonia solanacearum and Alternaria alternata.CONCLUSIONS: CAFFEOYL-COA 3-O-METHYLTRANSFERASE 6/6L can regulate the S/G ratio of lignin monomers and may affect tobacco bacterial wilt and brown spot disease resistance by disturbing phenylpropane and terpene metabolism in leaves and roots of Nicotiana tabacum, such as soyasaponin Bb.PMID:37868314 | PMC:PMC10585270 | DOI:10.3389/fpls.2023.1216702

ERJ Open Res. 2023 Oct 2;9(5):00269-2023. doi: 10.1183/23120541.00269-2023. eCollection 2023 Sep.ABSTRACTRATIONALE: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.METHODS: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study.MEASUREMENTS AND MAIN RESULTS: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12-18 months.CONCLUSION: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.PMID:37868143 | PMC:PMC10588792 | DOI:10.1183/23120541.00269-2023

PeerJ. 2023 Oct 18;11:e16177. doi: 10.7717/peerj.16177. eCollection 2023.ABSTRACTTrace elements play a crucial role in the growth and bioactive substance content of medicinal plants, but their utilization efficiency in soil is often low. In this study, soil and Aconitum carmichaelii samples were collected and measured from 22 different locations, followed by an analysis of the relationship between trace elements and the yield and alkaloid content of the plants. The results indicated a significant positive correlation between zinc, trace elements in the soil, and the yield and alkaloid content of A. carmichaelii. Subsequent treatment of A. carmichaelii with both bulk zinc oxide (ZnO) and zinc oxide nanoparticles (ZnO NPs) demonstrated that the use of ZnO NPs significantly enhanced plant growth and monoester-type alkaloid content. To elucidate the underlying mechanisms responsible for these effects, metabolomic analysis was performed, resulting in the identification of 38 differentially expressed metabolites in eight metabolic pathways between the two treatments. Additionally, significant differences were observed in the rhizosphere bacterial communities, with Bacteroidota and Actinobacteriota identified as valuable biomarkers for ZnO NP treatment. Covariation analysis further revealed significant correlations between specific microbial communities and metabolite expression levels. These findings provide compelling evidence that nanoscale zinc exhibits much higher utilization efficiency compared to traditional zinc fertilizer.PMID:37868063 | PMC:PMC10590109 | DOI:10.7717/peerj.16177

Comput Struct Biotechnol J. 2023 Oct 12;21:4933-4943. doi: 10.1016/j.csbj.2023.10.016. eCollection 2023.ABSTRACTThe study of the respiratory microbiome has entered a multi-omic era. Through integrating different omic data types such as metagenome, metatranscriptome, metaproteome, metabolome, culturome and radiome surveyed from respiratory specimens, holistic insights can be gained on the lung microbiome and its interaction with host immunity and inflammation in respiratory diseases. The power of multi-omics have moved the field forward from associative assessment of microbiome alterations to causative understanding of the lung microbiome in the pathogenesis of chronic, acute and other types of respiratory diseases. However, the application of multi-omics in respiratory microbiome remains with unique challenges from sample processing, data integration, and downstream validation. In this review, we first introduce the respiratory sample types and omic data types applicable to studying the respiratory microbiome. We next describe approaches for multi-omic integration, focusing on dimensionality reduction, multi-omic association and prediction. We then summarize progresses in the application of multi-omics to studying the microbiome in respiratory diseases. We finally discuss current challenges and share our thoughts on future promises in the field.PMID:37867968 | PMC:PMC10585227 | DOI:10.1016/j.csbj.2023.10.016

iScience. 2023 Oct 4;26(11):108109. doi: 10.1016/j.isci.2023.108109. eCollection 2023 Nov 17.ABSTRACTThe host-microbiome associations occurring on the skin of vertebrates significantly influence hosts' health. However, the factors mediating their interactions remain largely unknown. Herein, we used integrated technical and ecological frameworks to investigate the skin metabolites sustaining a beneficial symbiosis between tree frogs and bacteria. We characterize macrocyclic acylcarnitines as the major metabolites secreted by the frogs' skin and trace their origin to an enzymatic unbalance of carnitine palmitoyltransferases. We found that these compounds colocalize with bacteria on the skin surface and are mostly represented by members of the Pseudomonas community. We showed that Pseudomonas sp. MPFS isolated from frogs' skin can exploit acylcarnitines as its sole carbon and nitrogen source, and this metabolic capability is widespread in Pseudomonas. We summarize frogs' multiple mechanisms to filter environmental bacteria and highlight that acylcarnitines likely evolved for another function but were co-opted to provide nutritional benefits to the symbionts.PMID:37867936 | PMC:PMC10587524 | DOI:10.1016/j.isci.2023.108109

Vavilovskii Zhurnal Genet Selektsii. 2023 Sep;27(5):530-538. doi: 10.18699/VJGB-23-64.ABSTRACTThe etiology of essential hypertension is intricate, since it employs simultaneously various body systems related to the regulation of blood pressure in one way or another: the sympathetic nervous system, renin-angiotensin-aldosterone and hypothalamic-pituitary-adrenal systems, renal and endothelial mechanisms. The pathogenesis of hypertension is influenced by a variety of both genetic and environmental factors, which determines the heterogeneity of the disease in human population. Hence, there is a need to perform research on experimental models - inbred animal strains, one of them being ISIAH rat strain, which is designed to simulate inherited stress-induced arterial hypertension as close as possible to primary (or essential) hypertension in humans. To determine specific markers of diseases, various omics technologies are applied, including metabolomics, which makes it possible to evaluate the content of low-molecular compounds - amino acids, lipids, carbohydrates, nucleic acids fragments - in biological samples available for clinical analysis (blood and urine). We analyzed the metabolic profile of the blood serum of male ISIAH rats with a genetic stress-dependent form of arterial hypertension in comparison with the normotensive WAG rats. Using the method of nuclear magnetic resonance spectroscopy (NMR spectroscopy), 56 metabolites in blood serum samples were identified, 18 of which were shown to have significant interstrain differences in serum concentrations. Statistical analysis of the data obtained showed that the hypertensive status of ISIAH rats is characterized by increased concentrations of leucine, isoleucine, valine, myo-inositol, isobutyrate, glutamate, glutamine, ornithine and creatine phosphate, and reduced concentrations of 2-hydroxyisobutyrate, betaine, tyrosine and tryptophan. Such a ratio of the metabolite concentrations is associated with changes in the regulation of glucose metabolism (metabolic markers - leucine, isoleucine, valine, myo-inositol), of nitric oxide synthesis (ornithine) and catecholamine pathway (tyrosine), and with inflammatory processes (metabolic markers - betaine, tryptophan), all of these changes being typical for hypertensive status. Thus, metabolic profiling of the stress-dependent form of arterial hypertension seems to be an important result for a personalized approach to the prevention and treatment of hypertensive disease.PMID:37867609 | PMC:PMC10587007 | DOI:10.18699/VJGB-23-64

Biochem Pharmacol. 2023 Oct 20:115867. doi: 10.1016/j.bcp.2023.115867. Online ahead of print.ABSTRACTTransporter-mediated drug-drug interactions (DDIs) are assessed using probe drugs and in vitro and in vivo models during drug development. The utility of endogenous metabolites as transporter biomarkers is emerging for prediction of DDIs during early phases of clinical trials. Endogenous metabolites such as pyridoxic acid and kynurenic acid have shown potential to predict DDIs mediated by organic anion transporters (OAT1 and OAT3). However, these metabolites have not been assessed in rats for their utility in prediction of DDIs. Therefore, we carried out a rat pharmacokinetic DDI study using probenecid and furosemide as OAT inhibitor and substrate, respectively. Probenecid administration led to a 3.8-fold increase in the blood concentrations and 3-fold decrease in renal clearance of furosemide. High inter-individual and intra-day variability in pyridoxic acid and kynurenic acid, and no or moderate effect of probenecid administration on these metabolites suggest their limited utility for prediction of Oat-mediated DDI in rats. Therefore, rat blood and urine samples were further analysed using untargeted metabolomics. Twenty-one m/z features (out of >8000 detected features) were identified as putative biomarkers of rat Oat1 and Oat3 using a robust biomarker qualification approach. These m/z features belong to metabolic pathways such as fatty acid analogue, peptides, prostaglandin analogues, bile acid derivatives, flavonoids, phytoconstituents, and steroids, and can be used as a panel to decrease variability caused by processes other than Oats. When validated, these putative biomarkers will be useful in predicting DDIs caused by Oats in rats.PMID:37866801 | DOI:10.1016/j.bcp.2023.115867

Clin Immunol. 2023 Oct 20:109812. doi: 10.1016/j.clim.2023.109812. Online ahead of print.ABSTRACTSynovial fluid (SF) extracellular vesicles (EVs) play a pathogenic role in osteoarthritis (OA). However, the surface markers, cell and tissue origins, and effectors of these EVs are largely unknown. We found that SF EVs contained 692 peptides that were positively associated with knee radiographic OA severity; 57.4% of these pathogenic peptides were from 46 proteins of the immune system, predominantly the innate immune system. CSPG4, BGN, NRP1, and CD109 are the major surface markers of pathogenic SF EVs. Genes encoding surface marker CSPG4 and CD109 were highly expressed by chondrocytes from damaged cartilage, while VISG4, MARCO, CD163 and NRP1 were enriched in the synovial immune cells. The frequency of CSPG4+ and VSIG4+ EV subpopulations in OA SF was high. We conclude that pathogenic SF EVs carry knee OA severity-associated proteins and specific surface markers, which could be developed as a new source of diagnostic biomarkers or therapeutic targets in OA.PMID:37866785 | DOI:10.1016/j.clim.2023.109812