Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Polydopamine Nanoparticle-Based Combined Chemotherapy and Photothermal Therapy for the Treatment of Liver Cancer

Fri, 26/07/2024 - 12:00
ACS Appl Mater Interfaces. 2024 Jul 26. doi: 10.1021/acsami.4c08491. Online ahead of print.ABSTRACTPolydopamine nanoparticles (PDA NPs) are proposed as an anti-cancer tool against hepatocellular carcinoma through the combination of near-infrared (NIR)-mediated hyperthermia and loading with a chemotherapeutic drug, sorafenib (SRF). Cell membranes isolated from a liver cancer cell line (HepG2) have been exploited for the coating of the nanoparticles (thus obtaining CM-SRF-PDA NPs), to promote homotypic targeting toward cancer cells. The selective targeting ability and the combined photothermal and chemotherapeutic activity of the CM-SRF-PDA NPs following NIR irradiation have been evaluated on cell cultures in static and dynamic conditions, besides three-dimensional culture models. Eventually, the therapeutic effectiveness of the proposed approach has also been tested ex ovo on HepG2 spheroid-grafted quail embryos. This comprehensive investigation, supported by proteomic analysis, showed the effectiveness of the proposed nanoplatform and strongly suggests further pre-clinical testing in the treatment of liver cancer.PMID:39058979 | DOI:10.1021/acsami.4c08491

Hypoxic-Ischemic Insult Alters Polyamine and Neurotransmitter Abundance in the Specific Neonatal Rat Brain Subregions

Fri, 26/07/2024 - 12:00
ACS Chem Neurosci. 2024 Jul 26. doi: 10.1021/acschemneuro.4c00190. Online ahead of print.ABSTRACTNeonatal hypoxic-ischemic (HI) brain insult is a major cause of neonatal mortality and morbidity. To assess the underlying pathological mechanisms, we mapped the spatiotemporal changes in polyamine, amino acid, and neurotransmitter levels, following HI insult (by the Rice-Vannucci method) in the brains of seven-day-old rat pups. Matrix-assisted laser desorption/ionization mass spectrometry imaging of chemically modified small-molecule metabolites by 4-(anthracen-9-yl)-2-fluoro-1-methylpyridin-1-ium iodide revealed critical HI-related metabolomic changes of 22 metabolites in 14 rat brain subregions, much earlier than light microscopy detected signs of neuronal damage. For the first time, we demonstrated excessive polyamine oxidation and accumulation of 3-aminopropanal in HI neonatal brains, which was later accompanied by neuronal apoptosis enhanced by increases in glycine and norepinephrine in critically affected brain regions. Specifically, putrescine, cadaverine, and 3-aminopropanal increased significantly as early as 12 h postinsult, mainly in motor and somatosensory cortex, hippocampus, and midbrain, followed by an increase in norepinephrine 24 h postinsult, which was predominant in the caudate putamen, the region most vulnerable to HI. The decrease of γ-aminobutyric acid (GABA) and the continuous dysregulation of the GABAergic system together with low taurine levels up to 36 h sustained progressive neurodegenerative cellular processes. The molecular alterations presented here at the subregional rat brain level provided unprecedented insight into early metabolomic changes in HI-insulted neonatal brains, which may further aid in the identification of novel therapeutic targets for the treatment of neonatal HI encephalopathy.PMID:39058922 | DOI:10.1021/acschemneuro.4c00190

Integrated Proteomics and Metabolomics Reveal Altered Metabolic Regulation of Xanthobacter autotrophicus under Electrochemical Water-Splitting Conditions

Fri, 26/07/2024 - 12:00
ACS Appl Mater Interfaces. 2024 Jul 26. doi: 10.1021/acsami.4c07363. Online ahead of print.ABSTRACTBiological-inorganic hybrid systems are a growing class of technologies that combine microorganisms with materials for a variety of purposes, including chemical synthesis, environmental remediation, and energy generation. These systems typically consider microorganisms as simple catalysts for the reaction of interest; however, other metabolic activity is likely to have a large influence on the system performance. The investigation of biological responses to the hybrid environment is thus critical to the future development and optimization. The present study investigates this phenomenon in a recently reported hybrid system that uses electrochemical water splitting to provide reducing equivalents to the nitrogen-fixing bacteria Xanthobacter autotrophicus for efficient reduction of N2 to biomass that may be used as fertilizer. Using integrated proteomic and metabolomic methods, we find a pattern of differentiated metabolic regulation under electrochemical water-splitting (hybrid) conditions with an increase in carbon fixation products glycerate-3-phosphate and acetyl-CoA that suggests a high energy availability. We further report an increased expression of proteins of interest, namely, those responsible for nitrogen fixation and assimilation, which indicate increased rates of nitrogen fixation and support previous observations of faster biomass accumulation in the hybrid system compared to typical planktonic growth conditions. This work complicates the inert catalyst view of biological-inorganic hybrids while demonstrating the power of multiomics analysis as a tool for deeper understanding of those systems.PMID:39058742 | DOI:10.1021/acsami.4c07363

Comments on "Characterization of Selenium Speciation in Se-Enriched Crops: Crop Selection Approach"

Fri, 26/07/2024 - 12:00
J Agric Food Chem. 2024 Jul 26. doi: 10.1021/acs.jafc.4c02509. Online ahead of print.NO ABSTRACTPMID:39058297 | DOI:10.1021/acs.jafc.4c02509

Molecular mechanisms of temperature tolerance plasticity in an arthropod

Fri, 26/07/2024 - 12:00
Genome Biol Evol. 2024 Jul 26:evae165. doi: 10.1093/gbe/evae165. Online ahead of print.ABSTRACTHow species thrive in a wide range of environments is a major focus of evolutionary biology. For many species, limited genetic diversity or gene flow among habitats means that phenotypic plasticity must play an important role in their capacity to tolerate environmental heterogeneity and to colonize new habitats. However, we have a limited understanding of the molecular components that govern plasticity in ecologically relevant phenotypes. We examined this hypothesis in a spider species (Stegodyphus dumicola) with extremely low species-wide genetic diversity that nevertheless occupies a broad range of thermal environments. We determined phenotypic responses to temperature stress in individuals from four climatic zones using common garden acclimation experiments to disentangle phenotypic plasticity from genetic adaptations. Simultaneously, we created data sets on multiple molecular modalities: the genome, the transcriptome, the methylome, the metabolome and the bacterial microbiome to determine associations with phenotypic responses. Analyses of phenotypic and molecular associations reveal that acclimation responses in the transcriptome and metabolome correlate with patterns of phenotypic plasticity in temperature tolerance. Surprisingly, genes whose expression seemed to be involved in plasticity in temperature tolerance were generally highly methylated contradicting the idea that DNA methylation stabilizes gene expression. This suggests that the function of DNA methylation in invertebrates varies not only among species but also among genes. The bacterial microbiome was stable across the acclimation period; combined with our previous demonstrations that the microbiome is temporally stable in wild populations, this is convincing evidence that the microbiome does not facilitate plasticity in temperature tolerance. Our results suggest that population-specific variation in temperature tolerance among acclimation temperatures appears to result from the evolution of plasticity in mainly gene expression.PMID:39058286 | DOI:10.1093/gbe/evae165

Physical performance and plasma metabolic profile as potential prognostic factors in metastatic lung cancer patients

Fri, 26/07/2024 - 12:00
Eur J Clin Invest. 2024 Jul 26:e14288. doi: 10.1111/eci.14288. Online ahead of print.ABSTRACTBACKGROUND: Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non-small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells.METHODS: This prospective cohort study included 55 metastatic NSCLC patients and seven age-matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis.RESULTS: We observed a higher survival rate in NSCLC patients with high performance in the timed up-and-go (+320%; p = .007), sit-to-stand (+256%; p = .01) and six-minute walking (+323%; p = .002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (p > .05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (-54.2%; p < .0001) and cell proliferation (-44.9%; p = .007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance.CONCLUSION: These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism.PMID:39058257 | DOI:10.1111/eci.14288

Metabolome and Its Mechanism Profiling in the Synergistic Toxic Effects Induced by Co-Exposure of Tenuazonic Acid and Patulin in Caco-2 Cells

Fri, 26/07/2024 - 12:00
Toxins (Basel). 2024 Jul 15;16(7):319. doi: 10.3390/toxins16070319.ABSTRACTTenuazonic acid (TeA), usually found in cereals, fruits, vegetables, oil crops, and their products, was classified as one of the highest public health problems by EFSA as early as 2011, but it has still not been regulated by legislation due to the limited toxicological profile. Moreover, it has been reported that the coexistence of TeA and patulin (PAT) has been found in certain agricultural products; however, there are no available data about the combined toxicity. Considering that the gastrointestinal tract is the physiological barrier of the body, it would be the first target site at which exogenous substances interact with the body. Thus, we assessed the combined toxicity (cell viability, ROS, CAT, and ATP) in Caco-2 cells using mathematical modeling (Chou-Talalay) and explored mechanisms using non-targeted metabolomics and molecular biology methods. It revealed that the co-exposure of TeA + PAT (12.5 μg/mL + 0.5 μg/mL) can induce enhanced toxic effects and more severe oxidative stress. Mechanistically, the lipid and amino acid metabolisms and PI3K/AKT/FOXO signaling pathways were mainly involved in the TeA + PAT-induced synergistic toxic effects. Our study not only enriches the scientific basis for the development of regulatory policies but also provides potential targets and treatment options for alleviating toxicities.PMID:39057959 | DOI:10.3390/toxins16070319

First Report on Mycotoxin Contamination of Hops (<em>Humulus lupulus</em> L.)

Fri, 26/07/2024 - 12:00
Toxins (Basel). 2024 Jun 26;16(7):293. doi: 10.3390/toxins16070293.ABSTRACTThe presence of mycotoxins and other toxic metabolites in hops (Humulus lupulus L.) was assessed for the first time. In total, 62 hop samples were sampled in craft breweries, and analyzed by a multi-toxin LS-MS/MS method. The study collected samples from craft breweries in all of the Croatian counties and statistically compared the results. Based on previous reports on Alternaria spp. and Fusarium spp. contamination of hops, the study confirmed the contamination of hops with these toxins. Alternaria toxins, particularly tenuazonic acid, were found in all tested samples, while Fusarium toxins, including deoxynivalenol, were present in 98% of samples. However, no Aspergillus or Penicillium metabolites were detected, indicating proper storage conditions. In addition to the Alternaria and Fusarium toxins, abscisic acid, a drought stress indicator in hops, was also detected, as well as several unspecific metabolites. The findings suggest the need for monitoring, risk assessment, and potential regulation of Alternaria and Fusarium toxins in hops to ensure the safety of hop usage in the brewing and pharmaceutical industries. Also, four local wild varieties were tested, with similar results to the commercial varieties for toxin contamination, but the statistically significant regional differences in toxin occurrence highlight the importance and need for targeted monitoring.PMID:39057933 | DOI:10.3390/toxins16070293

A Multiomics, Molecular Atlas of Breast Cancer Survivors

Fri, 26/07/2024 - 12:00
Metabolites. 2024 Jul 20;14(7):396. doi: 10.3390/metabo14070396.ABSTRACTBreast cancer imposes a significant burden globally. While the survival rate is steadily improving, much remains to be elucidated. This observational, single time point, multiomic study utilizing genomics, proteomics, targeted and untargeted metabolomics, and metagenomics in a breast cancer survivor (BCS) and age-matched healthy control cohort (N = 100) provides deep molecular phenotyping of breast cancer survivors. In this study, the BCS cohort had significantly higher polygenic risk scores for breast cancer than the control group. Carnitine and hexanoyl carnitine were significantly different. Several bile acid and fatty acid metabolites were significantly dissimilar, most notably the Omega-3 Index (O3I) (significantly lower in BCS). Proteomic and metagenomic analyses identified group and pathway differences, which warrant further investigation. The database built from this study contributes a wealth of data on breast cancer survivorship where there has been a paucity, affording the ability to identify patterns and novel insights that can drive new hypotheses and inform future research. Expansion of this database in the treatment-naïve, newly diagnosed, controlling for treatment confounders, and through the disease progression, can be leveraged to profile and contextualize breast cancer and breast cancer survivorship, potentially leading to the development of new strategies to combat this disease and improve the quality of life for its victims.PMID:39057719 | DOI:10.3390/metabo14070396

Diagnostic Potential of Alternations of Bile Acid Profiles in the Plasma of Patients with Huntington's Disease

Fri, 26/07/2024 - 12:00
Metabolites. 2024 Jul 20;14(7):394. doi: 10.3390/metabo14070394.ABSTRACTHuntington's disease (HD) is characterized by progressive involuntary chorea movements and cognitive decline. Recent research indicates that metabolic disturbance may play a role in its pathogenesis. Bile acids, produced during cholesterol metabolism in the liver, have been linked to neurodegenerative conditions. This study investigated variations in plasma bile acid profiles among individuals with HD. Plasma levels of 16 primary and secondary bile acids and their conjugates were analyzed in 20 healthy controls and 33 HD patients, including 24 with symptoms (symHD) and 9 carriers in the presymptomatic stage (preHD). HD patients exhibited significantly higher levels of glycochenodeoxycholic acid (GCDCA) and glycoursodeoxycholic acid (GUDCA) compared to healthy controls. Conversely, isolithocholic acid levels were notably lower in the HD group. Neurotoxic bile acids (glycocholic acid (GCA) + glycodeoxycholic acid (GDCA) + GCDCA) were elevated in symHD patients, while levels of neuroprotective bile acids (ursodeoxycholic acid (UDCA) + GUDCA + tauroursodeoxycholic acid (TUDCA)) were higher in preHD carriers, indicating a compensatory response to early neuronal damage. These results underscore the importance of changes in plasma bile acid profiles in HD and their potential involvement in disease mechanisms. The identified bile acids (GCDCA, GUDCA, and isolithocholic acid) could potentially serve as markers to distinguish between HD stages and healthy individuals. Nonetheless, further research is warranted to fully understand the clinical implications of these findings and their potential as diagnostic or therapeutic tools for HD.PMID:39057717 | DOI:10.3390/metabo14070394

Hunting Metabolic Biomarkers for Exposure to Per- and Polyfluoroalkyl Substances: A Review

Fri, 26/07/2024 - 12:00
Metabolites. 2024 Jul 19;14(7):392. doi: 10.3390/metabo14070392.ABSTRACTPer- and polyfluoroalkyl substances (PFAS) represent a class of persistent synthetic chemicals extensively utilized across industrial and consumer sectors, raising substantial environmental and human health concerns. Epidemiological investigations have robustly linked PFAS exposure to a spectrum of adverse health outcomes. Altered metabolites stand as promising biomarkers, offering insights into the identification of specific environmental pollutants and their deleterious impacts on human health. However, elucidating metabolic alterations attributable to PFAS exposure and their ensuing health effects has remained challenging. In light of this, this review aims to elucidate potential biomarkers of PFAS exposure by presenting a comprehensive overview of recent metabolomics-based studies exploring PFAS toxicity. Details of PFAS types, sources, and human exposure patterns are provided. Furthermore, insights into PFAS-induced liver toxicity, reproductive and developmental toxicity, cardiovascular toxicity, glucose homeostasis disruption, kidney toxicity, and carcinogenesis are synthesized. Additionally, a thorough examination of studies utilizing metabolomics to delineate PFAS exposure and toxicity biomarkers across blood, liver, and urine specimens is presented. This review endeavors to advance our understanding of PFAS biomarkers regarding exposure and associated toxicological effects.PMID:39057715 | DOI:10.3390/metabo14070392

Alteration of Fecal Microbiota, Fecal Metabolites, and Serum Metabolites in Dairy Cows with Pre-Retained Placenta

Fri, 26/07/2024 - 12:00
Metabolites. 2024 Jul 15;14(7):386. doi: 10.3390/metabo14070386.ABSTRACTRetained placenta (RP) affects lactation and fertility in dairy cows and causes economic losses to the dairy industry. Therefore, screening for early warning of this disease is important. This study used multi omics techniques to reveal the metabolic differences of dairy cows before RP onset and to find potential warning markers. Fecal samples and serum samples of 90 healthy Holstein cows were collected 7 days pre-calving; 10 healthy and 10 RP cows were enrolled according to normal expulsion of fetal membranes after calving. Fecal samples were subjected to 16S rRNA sequencing and untargeted metabolomics analysis, while plasma was analyzed using targeted metabolomics. Pathogenic bacteria levels increased in the intestines of cows with RP compared to those in healthy cows. Lipid metabolites constituted the largest proportion of differential metabolites between feces and plasma. Six potential warning markers for RP in cows were identified, including two fecal microbiomics markers (Oscillospiraceae UCG-005 and Escherichia-Shigella), one fecal untargeted metabolomics marker (N-acetylmuramic acid), and three plasma targeted metabolomics markers (glycylcholic acid-3 sulfate, 7-ketolithocholic acid, and 12-ketolithocholic acid). These biomarkers can predict RP occurrence in the early perinatal period. These results lay a theoretical foundation for early nutritional intervention and pathogenesis research in dairy cows.PMID:39057709 | DOI:10.3390/metabo14070386

Challenges of Spatially Resolved Metabolism in Cancer Research

Fri, 26/07/2024 - 12:00
Metabolites. 2024 Jul 11;14(7):383. doi: 10.3390/metabo14070383.ABSTRACTStable isotope-resolved metabolomics comprises a critical set of technologies that can be applied to a wide variety of systems, from isolated cells to whole organisms, to define metabolic pathway usage and responses to perturbations such as drugs or mutations, as well as providing the basis for flux analysis. As the diversity of stable isotope-enriched compounds is very high, and with newer approaches to multiplexing, the coverage of metabolism is now very extensive. However, as the complexity of the model increases, including more kinds of interacting cell types and interorgan communication, the analytical complexity also increases. Further, as studies move further into spatially resolved biology, new technical problems have to be overcome owing to the small number of analytes present in the confines of a single cell or cell compartment. Here, we review the overall goals and solutions made possible by stable isotope tracing and their applications to models of increasing complexity. Finally, we discuss progress and outstanding difficulties in high-resolution spatially resolved tracer-based metabolic studies.PMID:39057706 | DOI:10.3390/metabo14070383

Impact of Varying Dietary Calcium Contents on the Gut Metabolomics of Yunnan Semi-Fine Wool Sheep (Ovis aries)

Fri, 26/07/2024 - 12:00
Metabolites. 2024 Jul 10;14(7):381. doi: 10.3390/metabo14070381.ABSTRACTYunnan semi-fine wool (YSFW) is a recently developed dual-purpose (meat and wool) sheep breed mainly found in Yunnan Province, China. Moreover, dietary calcium is essential for animal health and productivity. The current experiment aimed to investigate the impact of dietary calcium on sheep gut metabolite profile. For this, thirty YSFW rams (male, age = 10 months, and body weight = 40.37 ± 0.49 kg) were randomized into three groups (n = 10 rams/group), followed by a completely randomized design, and the groups were allotted to one of three dietary calcium levels (Q_1 = 0.50%, Q_3 = 0.73%, and Q_5 = 0.98% on a dry basis). The rams were fed ad libitum by feeding twice a day (at 08:00 and 17:00 h/day) throughout the experimental period (44 day). On the 21st day of the experiment, fecal samples were collected from 27 rams (9/group) and untargeted metabolite profiling was performed by using ultra-performance liquid chromatography. The PCA plot showed that the Q_5 group metabolites were clustered more tightly than for Q_1 and Q_3, respectively. The tightly clustering molecules were mainly alkaloids and their derivatives, benzenoids, lignans and related compounds, lipids, nucleotides, organic acids, and nitrogenous-based derivatives. According to the Kyoto Encyclopedia of Genes and Genomes pathway analysis, these molecules potentially contribute to metabolic pathways, biosynthesis of secondary metabolites, proteinaceous compounds, and the metabolism of the protein derivatives, particularly amino acids. The PLS-DA plots revealed a significant difference between the Q_1, Q_3, and Q_5 groups, suggesting that Q_5 had a clear separation across the groups. Based on the metabolomic analysis, feeding different levels of dietary calcium significantly changed the metabolomic profile of YSFW rams, which primarily entails metabolic pathways such as energy, protein, and lipid metabolism.PMID:39057704 | DOI:10.3390/metabo14070381

Early Metabolomic and Immunologic Biomarkers as Prognostic Indicators for COVID-19

Fri, 26/07/2024 - 12:00
Metabolites. 2024 Jul 9;14(7):380. doi: 10.3390/metabo14070380.ABSTRACTThis prospective study in Hong Kong aimed at identifying prognostic metabolomic and immunologic biomarkers for Coronavirus Disease 2019 (COVID-19). We examined 327 patients, mean age 55 (19-89) years, in whom 33.6% were infected with Omicron and 66.4% were infected with earlier variants. The effect size of disease severity on metabolome outweighed others including age, gender, peak C-reactive protein (CRP), vitamin D and peak viral levels. Sixty-five metabolites demonstrated strong associations and the majority (54, 83.1%) were downregulated in severe disease (z score: -3.30 to -8.61). Ten cytokines/chemokines demonstrated strong associations (p < 0.001), and all were upregulated in severe disease. Multiple pairs of metabolomic/immunologic biomarkers showed significant correlations. Fourteen metabolites had the area under the receiver operating characteristic curve (AUC) > 0.8, suggesting a high predictive value. Three metabolites carried high sensitivity for severe disease: triglycerides in medium high-density lipoprotein (MHDL) (sensitivity: 0.94), free cholesterol-to-total lipids ratio in very small very-low-density lipoprotein (VLDL) (0.93), cholesteryl esters-to-total lipids ratio in chylomicrons and extremely large VLDL (0.92);whereas metabolites with the highest specificity were creatinine (specificity: 0.94), phospholipids in large VLDL (0.94) and triglycerides-to-total lipids ratio in large VLDL (0.93). Five cytokines/chemokines, namely, interleukin (IL)-6, IL-18, IL-10, macrophage inflammatory protein (MIP)-1b and tumour necrosis factor (TNF)-a, had AUC > 0.8. In conclusion, we demonstrated a tight interaction and prognostic potential of metabolomic and immunologic biomarkers enabling an outcome-based patient stratification.PMID:39057703 | DOI:10.3390/metabo14070380

Unraveling the Evolutionary Diet Mismatch and Its Contribution to the Deterioration of Body Composition

Fri, 26/07/2024 - 12:00
Metabolites. 2024 Jul 7;14(7):379. doi: 10.3390/metabo14070379.ABSTRACTOver the millennia, patterns of food consumption have changed; however, foods were always whole foods. Ultra-processed foods (UPFs) have been a very recent development and have become the primary food source for many people. The purpose of this review is to propose the hypothesis that, forsaking the evolutionary dietary environment, and its complex milieu of compounds resulting in an extensive metabolome, contributes to chronic disease in modern humans. This evolutionary metabolome may have contributed to the success of early hominins. This hypothesis is based on the following assumptions: (1) whole foods promote health, (2) essential nutrients cannot explain all the benefits of whole foods, (3) UPFs are much lower in phytonutrients and other compounds compared to whole foods, and (4) evolutionary diets contributed to a more diverse metabolome. Evidence will be presented to support this hypothesis. Nutrition is a matter of systems biology, and investigating the evolutionary metabolome, as compared to the metabolome of modern humans, will help elucidate the hidden connections between diet and health. The effect of the diet on the metabolome may also help shape future dietary guidelines, and help define healthy foods.PMID:39057702 | DOI:10.3390/metabo14070379

Metabolic and Lipid Biomarkers for Pathogenic Algae, Fungi, Cyanobacteria, Mycobacteria, Gram-Positive Bacteria, and Gram-Negative Bacteria

Fri, 26/07/2024 - 12:00
Metabolites. 2024 Jul 6;14(7):378. doi: 10.3390/metabo14070378.ABSTRACTThe utilization of metabolomics and lipidomics analytical platforms in the study of pathogenic microbes is slowly expanding. These research approaches will significantly contribute to the establishment of microbial metabolite and lipid databases of significant value to all researchers in microbiology. In this review, we present a high-level overview of some examples of biomarkers that can be used to detect the presence of microbes, monitor the expansion/decline of a microbe population, and add to our understanding of microbe biofilms and pathogenicity. In addition, increased knowledge of the metabolic functions of pathogenic microbes can contribute to our understanding of microbes that are utilized in diverse industrial applications. Our review focuses on lipids, secondary metabolites, and non-ribosomal peptides that can be monitored using electrospray ionization high-resolution mass spectrometry (ESI-HRMS).PMID:39057701 | DOI:10.3390/metabo14070378

Metabolomics of Benzene Exposure and Development of Biomarkers for Exposure Hazard Assessment

Fri, 26/07/2024 - 12:00
Metabolites. 2024 Jul 3;14(7):377. doi: 10.3390/metabo14070377.ABSTRACTBenzene, a common industrial solvent, poses significant health risks including poisoning and hematopoietic diseases. However, its precise toxicity mechanisms remain unclear. To assess the health impact of prolonged benzene exposure through metabolomic analyses of exposed workers and benzene-poisoned mice, aiming to identify biomarkers and minimize occupational hazards. This study compared 18 benzene-exposed workers with 18 non-exposed workers, matching for age, lifestyle, and BMI. The metabolites in the workers' samples were analyzed using ultra-high-performance liquid chromatography and mass spectrometry. A larger study included 118 exposed and 158 non-exposed workers, incorporating surveys and routine blood and urine tests with differential metabolites targeted via an enzyme-linked immunosorbent assay. The animal studies consisted of two 15- and 60-day benzene staining and control experiments on 28 C57BL/6J mice, followed by sample collection and organ analysis. The data analysis employed eXtensible Computational Mass Spectrometry (XCMS), Python, MetaboAnalyst 6.0, and SPSS24.0. The exposed workers exhibited altered metabolites indicating external benzene exposure, lower glucose levels, and changes in white blood cell counts and urinary ketone bodies. The plasma metabolomics revealed disturbances in energy and lipid metabolism. The benzene-exposed mice displayed reduced weight gain, behavioral changes, and organ damage. Oxidative stress and abnormal purine and lipid metabolism were observed in both the long-term benzene-exposed workers and benzene-exposed mice. Metabolic markers for the early detection of benzene exposure hazards were identified, underscoring the need to mitigate occupational risks.PMID:39057700 | DOI:10.3390/metabo14070377

Investigation of the Functional Components in Health Beverages Made from <em>Polygonatum cyrtonema</em> Rhizomes Provides Primary Evidence to Support Their Claimed Health Benefits

Fri, 26/07/2024 - 12:00
Metabolites. 2024 Jul 3;14(7):376. doi: 10.3390/metabo14070376.ABSTRACTThis study aims to understand the functional component compositions of traditional herbal health beverages made from Polygonatum cyrtonema rhizomes and to reveal the pharmacodynamic chemical basis for their claimed health benefits. Two traditional methods, rhizome decoction and rhizome infusion, were used to make health herbal beverages, including "Huangjin" tea and "Huangjin" wine, respectively. The secondary metabolites of "Huangjin" beverages were investigated and compared by widely targeted metabolomics. The results clearly showed that the major functional components in "Huangjin" beverages were phenolic acids, flavonoids, and alkaloids. The "Huangjin" wine has a greater variety of flavonoids and alkaloids than "Huangjin" tea, and the functional components in "Huangjin" wine were more abundant than those in "Huangjin" tea. Homoisoflavones and amide alkaloids were the dominating flavonoids and alkaloids in "Huangjin" wine, respectively. Continuous rhizome infusion could not increase the content of functional components in "Huangjin" wine. In conclusion, this study not only provides primary evidence to support the claimed health benefits of "Huangjin" beverages but also suggests that making traditional herbal beverages by rhizome infusion has superior health benefits than making them by rhizome decoction, which is attributed to the higher yields of functional components extracted by Chinese liquor than hot water. Therefore, Chinese liquor shows advantages in its use as a superior binary ethanol-water solvent in making herbal health beverages to enhance the solubility of poorly water-soluble functional components.PMID:39057699 | DOI:10.3390/metabo14070376

Metabolomics and Multi-Omics Determination of Potential Plasma Biomarkers in PRV-1-Infected Atlantic Salmon

Fri, 26/07/2024 - 12:00
Metabolites. 2024 Jul 2;14(7):375. doi: 10.3390/metabo14070375.ABSTRACTMetabolomic analysis has been explored to search for disease biomarkers in humans for some time. The application to animal species, including fish, however, is still at the beginning. In the present study, we have used targeted and untargeted metabolomics to identify metabolites in the plasma of Atlantic salmon (Salmo salar) challenged with Piscine orthoreovirus (PRV-1), aiming to find metabolites associated with the progression of PRV-1 infection into heart and skeletal muscle inflammation (HSMI). The metabolomes of control and PRV-1-infected salmon were compared at three time points during disease development by employing different biostatistical approaches. Targeted metabolomics resulted in the determination of affected metabolites and metabolic pathways, revealing a substantial impact of PRV-1 infection on lipid homeostasis, especially on several (lyso)phosphatidylcholines, ceramides, and triglycerides. Untargeted metabolomics showed a clear separation of the treatment groups at later study time points, mainly due to effects on lipid metabolism pathways. In a subsequent multi-omics approach, we combined both metabolomics datasets with previously reported proteomics data generated from the same salmon plasma samples. Data processing with DIABLO software resulted in the identification of significant metabolites and proteins that were representative of the HSMI development in the salmon.PMID:39057698 | DOI:10.3390/metabo14070375

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