PubMed

Carbohydr Polym. 2023 Apr 15;306:120626. doi: 10.1016/j.carbpol.2023.120626. Epub 2023 Jan 26.ABSTRACTThe roots of Salvia miltiorrhiza have been used in Traditional Chinese Medicine for thousands of years. However, tons of aerial parts of this plant are usually discarded in the production of roots preparation. To make better use of these plant resources, the polysaccharide isolated from the aerial part of S. miltiorrhiza was investigated for its potential protection against intestinal diseases. A pectic polysaccharide (SMAP-1) was isolated and characterized being composed of homogalacturonan as the main chain and rhamnogalacturonan type I as ramified region, with side chains including arabinans and possible arabinogalactan type I and II. SMAP-1 exhibited robust protective effects against dextran sodium sulfate (DSS)-induced colitis and restored colitis symptoms, colonic inflammation, and barrier functions. Anti-oxidative effects were also observed by up-regulating Nrf2/Keap1 signaling pathway. Additionally, the level of serum 5-methoxyindole-3-carboxaldehyde (5-MC) was restored by SMAP-1 identified in metabolomic analysis, being correlated with the aforementioned effects. Protection against oxidative stress on intestinal porcine enterocyte cells (IPEC-J2) by 5-MC was observed through the activation of Nrf2/Keap1 system, as also shown by SMAP-1. In conclusion, SMAP-1 could be a promising candidate for colitis prevention, and 5-MC could be the signal metabolite of SMAP-1 in protecting against oxidative stress in the intestine.PMID:36746576 | DOI:10.1016/j.carbpol.2023.120626

Pharmacol Res. 2023 Feb 4:106687. doi: 10.1016/j.phrs.2023.106687. Online ahead of print.ABSTRACTAccumulating evidence indicates gut microbiota contributes to aging-related disorders. However, the exact mechanism underlying gut dysbiosis-related pathophysiological changes during aging remains largely unclear. In the current study, we first performed gut microbiota remodeling on old mice by fecal microbiota transplantation (FMT) from young mice, and then characterized the bacteria signature that was specifically altered by FMT. Our results revealed that FMT significantly improved natural aging-related systemic disorders, particularly exerted hepatoprotective effects, and improved glucose sensitivity, hepatosplenomegaly, inflammaging, antioxidative capacity and intestinal barrier. Moreover, FMT particularly increased the abundance of fecal A.muciniphila, which was almost nondetectable in old mice. Interestingly, A.muciniphila supplementation also exerted similar benefits with FMT on old mice. Notably, targeted metabolomics on short chain fatty acids (SCFAs) revealed that only acetic acid was consistently reversed by FMT. Then, acetic acid intervention exerted beneficial actions on both Caenorhabditis elegans and natural aging mice. In conclusion, our current study demonstrated that gut microbiota remodeling improved natural aging-related disorders through A.muciniphila and its derived acetic acid, suggesting that interventions with potent stimulative capacity on A. muciniphila growth and production of acetic acid was alternative and effective way to maintain healthy aging. DATA AVAILABILITY STATEMENT: The data of RNAseq and 16S rRNA gene sequencing can be accessed in NCBI with the accession number PRJNA848996 and PRJNA849355.PMID:36746362 | DOI:10.1016/j.phrs.2023.106687

Life Sci. 2023 Feb 4:121474. doi: 10.1016/j.lfs.2023.121474. Online ahead of print.ABSTRACTAIMS: Atopic dermatitis (AD) is a common chronic inflammatory skin disorder that affects up to 20 % of children and 10 % of adults worldwide; however, the exact molecular mechanisms remain largely unknown.MATERIALS AND METHODS: In this study, we used integrated transcriptomic and metabolomic analyses to study the potential mechanisms of 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like skin lesions.KEY FINDINGS: We found that DNCB induced AD-like skin lesions, including phenotypical and histomorphological alterations and transcriptional and metabolic alterations in mice. A total of 3413 differentially expressed metabolites were detected between DNCB-induced AD-like mice and healthy controls, which includes metabolites in taurine and hypotaurine metabolism, phenylalanine metabolism, biosynthesis of unsaturated fatty acids, tryptophan metabolism, arachidonic acid metabolism, pantothenate and CoA biosynthesis, pyrimidine metabolism, and glycerophospholipid metabolism pathways. Furthermore, the differentially expressed genes associated (DEGs) with these metabolic pathways were analyzed using RNA sequencing (RNA-seq), and we found that the expression of pyrimidine metabolism-associated genes was significantly increased. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the glycolysis/gluconeogenesis, glucagon signaling pathway and pentose phosphate pathway-associated metabolic genes were dramatically altered.SIGNIFICANCE: Our results explain the possible mechanism of AD at the gene and metabolite levels and provide potential targets for the development of clinical drugs for AD.PMID:36746357 | DOI:10.1016/j.lfs.2023.121474

Biomed J. 2023 Feb 4:S2319-4170(23)00005-7. doi: 10.1016/j.bj.2023.02.001. Online ahead of print.ABSTRACTCellular senescence is a complex process involving a close-to-irreversible arrest of the cell cycle, the acquisition of the senescence-associated secretory phenotype (SASP), as well as profound changes in the expression of cell surface proteins that determine the recognition of senescent cells by innate and cognate immune effectors including macrophages, NK, NKT and T cells. It is important to note that senescence can occur in a transient fashion to improve the homeostatic response of tissues to stress. Moreover, both the excessive generation and the insufficient elimination of senescent cells may contribute to pathological aging. Attempts are being made to identify the mechanisms through which senescent cell avoid their destruction by immune effectors. Such mechanisms involve the cell surface expression of immunosuppressive molecules including PD-L1 and PD-L2 to ligate PD-1 on T cells, as well as tolerogenic MHC class-I variants. In addition, senescent cells can secrete factors that attract immunosuppressive and pro-inflammatory cells into the microenvironment. Each of these immune evasion mechanism offers a target for therapeutic intervention, e.g., by blocking the interaction between PD-1 and PD-L1 or PD-L2, upregulating immunogenic MHC class-I molecules and eliminating immunosuppressive cell types. In addition, senescent cells differ in their antigenic makeup and immunopeptidome from their normal counterparts, hence offering the opportunity to stimulate immune response against senescence-associated antigens. Ideally, immunological anti-senescence strategies should succeed in selectively eliminating pathogenic senescent cells but spare homeostatic senescence.PMID:36746349 | DOI:10.1016/j.bj.2023.02.001

Environ Pollut. 2023 Feb 4:121220. doi: 10.1016/j.envpol.2023.121220. Online ahead of print.ABSTRACTEmerging evidence suggests that exposure to PM2.5 is associated with a high risk of nonalcoholic fatty liver disease (NAFLD). NAFLD is typically characterised by hepatic steatosis. However, the underlying mechanisms and critical components of PM2.5-induced hepatic steatosis remain to be elucidated. In this study, 10-month-old C57BL/6 female mice were exposed to PM2.5 from four cities in China (Taiyuan, Beijing, Hangzhou, and Guangzhou) via oropharyngeal aspiration every other day for four weeks. After the exposure period, hepatic lipid accumulation was evaluated by biochemical and histopathological analyses. The expression levels of genes related to lipid metabolism and metabolomic profiles were assessed in the mouse liver. The association between biomarkers of hepatic steatosis (hepatic Oil Red O staining area and serum and liver triglyceride contents) and typical components of PM2.5 was identified using Pearson correlation analysis. Oil Red O staining and biochemical results indicated that PM2.5 from four cities significantly induced hepatic lipid accumulation. The most severe hepatic steatosis was observed after Guangzhou PM2.5 exposure. Moreover, Guangzhou PM2.5-induced the most significant changes in gene expression associated with lipid metabolism, including increased hepatic fatty acid uptake and lipid droplet formation and decreased fatty acid synthesis and lipoprotein secretion. Contemporaneously, exposure to Guangzhou PM2.5 significantly perturbed hepatic lipid metabolism. According to metabolomic analysis, disturbed hepatic lipid metabolism was primarily concentrated in linoleic acid, α-linoleic acid, and arachidonic acid metabolism. Finally, correlation analysis revealed that copper (Cu) and other inorganic components, as well as the majority of polycyclic aromatic hydrocarbons (PAHs), were related to changes in biomarkers of hepatic steatosis. These findings showed that PM2.5 exposure caused hepatic steatosis in aged mice, which could be related to the critical chemical components of PM2.5. This study provides critical information regarding the components of PM2.5, which cause hepatic steatosis.PMID:36746292 | DOI:10.1016/j.envpol.2023.121220

Chemosphere. 2023 Feb 4:137998. doi: 10.1016/j.chemosphere.2023.137998. Online ahead of print.ABSTRACTChronic exposure to arsenic (As) remains a global public health concern and our understanding of the biological mechanisms underlying the adverse effects of As exposure remains incomplete. Here, we used a high-resolution metabolomics approach to examine how As affects metabolic pathways in humans. We selected 60 non-smoking adults from the Folic Acid and Creatine Trial (FACT). Inorganic (AsIII, AsV) and organic (monomethylarsonous acid [MMAs], dimethylarsinous Acid [DMAs]) As species were measured in blood and urine collected at baseline and at 12 weeks. Plasma metabolome profiles were measured using untargeted high-resolution mass spectrometry. Associations of blood and urinary As with 170 confirmed metabolites and >26,000 untargeted spectral features were modeled using a metabolome-wide association study (MWAS) approach. Models were adjusted for age, sex, visit, and BMI and corrected for false discovery rate (FDR). In the MWAS screening of confirmed metabolites, 17 were associated with ≥1 blood As species (FDR<0.05), including fatty acids, neurotransmitter metabolites, and amino acids. These results were consistent across blood As species and between blood and urine As. Untargeted MWAS identified 423 spectral features associated with ≥1 blood As species. Unlike the confirmed metabolites, untargeted model results were not consistent across As species, with AsV and DMAs showing distinct association patterns. Mummichog pathway analysis revealed 12 enriched metabolic pathways that overlapped with the 17 identified metabolites, including one carbon metabolism, tricarboxylic acid cycle, fatty acid metabolism, and purine metabolism. Exposure to As may affect numerous essential pathways that underlie the well-characterized associations of As with multiple chronic diseases.PMID:36746250 | DOI:10.1016/j.chemosphere.2023.137998

Fish Shellfish Immunol. 2023 Feb 4:108590. doi: 10.1016/j.fsi.2023.108590. Online ahead of print.ABSTRACTThe molecular processes underlying skin wound healing in several fish species have been elucidated in the last years, however, metabolomic insights are scarce. Here we report the skin mucus metabolome of wounded and non-wounded gilthead seabream (Sparus aurata) fed with silk fibroin microparticles, a functional additive considered to accelerate the wound healing process. The three experimental diets (commercial diet enriched with 0 mg (control), 50 mg or 100 mg of silk fibroin microparticles Kg-1) were administered for 30 days and thereafter, a skin wound was inflicted. Skin mucus was collected on day 30 of feeding and 7 days post-wounding and subjected to metabolomic analysis by Ultra Performance Liquid Chromatography coupled with a high-resolution quadrupole-orbitrap mass spectrometry. The most enriched metabolite class was amino acids and derivatives, followed by nucleotides, nucleosides and analogues and carbohydrates and their derivatives. Metabolomic profiles revealed that the diet had a more profound effect than wounding in skin mucus. Metabolic pathway analysis of significantly affected metabolites revealed perturbations in the aminoacyl t-RNA biosynthesis in the skin. In particular, skin wound resulted in a decreased methionine level in mucus. Further, silk fibroin supplementation increased methionine level in skin mucus, which correlated with several wound morphometric parameters that characterized the epithelial healing capacity in seabream. The results provided new insight into the physiological consequences of skin wounds and how these processes could be influenced by dietary manipulation.PMID:36746227 | DOI:10.1016/j.fsi.2023.108590

Bioresour Technol. 2023 Feb 4:128705. doi: 10.1016/j.biortech.2023.128705. Online ahead of print.ABSTRACTCordycepin is the key pharmacologically active compound of Cordyceps militaris, and various fermentation strategies have been developed to increase cordycepin production. This study aimed to investigate the effect of rotenone on cordycepin biosynthesis in submerged fermentation of C. militaris, and also to explore its possible induction mechanisms via multi-omics analysis. Adding 5 mg/L rotenone significantly increased the cordycepin production by 316.09%, along with mycelial growth inhibition and cell wall destruction. Moreover, transcriptomic analysis and metabolomic analysis revealed the accumulation of cordycepin was promoted by alterations in energy metabolism and amino acid metabolism pathways. Finally, the integration analysis of the two omics confirmed rotenone altered the nucleotide metabolism pathway toward adenosine and up-regulated the cordycepin synthesis genes (cns1-3) to convert adenosine to cordycepin. This work reports, for the first time, rotenone could act as an effective inducer of cordycepin synthesis.PMID:36746212 | DOI:10.1016/j.biortech.2023.128705

Aquat Toxicol. 2023 Feb 2;256:106415. doi: 10.1016/j.aquatox.2023.106415. Online ahead of print.ABSTRACTThe ecotoxicological and environmental impacts of glyphosate-based herbicides have received considerable attention due to their extensive use globally. However, the potential for adverse effects in cultured non-fish vertebrate species are commonly ignored. In this study, effects on growth, indicators of functional performance, gut microbial diversity, liver antioxidant responses and metabolite profiles were evaluated in soft-shelled turtle hatchlings (Pelodiscus sinensis) exposed to different concentrations of glyphosate-isopropylammonium (0, 0.02, 0.2, 2 and 20 mg/L). No significant changes in growth or functional performance (food intake, swimming speed), gut microbiota, and liver antioxidant responses (SOD and CAT activities, MDA content) were observed in exposed turtles. However, hepatic metabolite profiles revealed distinct perturbations that primarily involved amino acid metabolism in turtles exposed to environmentally relevant concentrations. Overall, our results suggested that metabolite profiles may be more sensitive than phenotypic or general physiological endpoints and gut microbiota profiling, and indicate a potential mechanism of hepatotoxicity caused by glyphosate-isopropylammonium based on untargeted metabolomics analysis. Furthermore, the toxicity of glyphosate at environmentally relevant concentrations might be relatively minor in aquatic turtle species.PMID:36746075 | DOI:10.1016/j.aquatox.2023.106415

Water Res. 2022 Nov 28;232:119434. doi: 10.1016/j.watres.2022.119434. Online ahead of print.ABSTRACTThe low efficiency of conventional complete denitrification, as well as the unstable nitrite supply for partial-denitrification coupled anammox (PD/A) restrict the efficient removal of nitrogen from industrial wastewaters. Herein, we proposed an optical strategy to bidirectionally regulate denitrification by introducing lights at different wavelengths, and the underlying mechanisms were elucidated accordingly. It turned out that yellow light at wavelength of 590 nm accelerated denitrification by 35.4%, while blue light delayed denitrification with stable nitrite accumulation above 86.9% and high nitrate removal (99.8%). Microbial physiology and viability further supported the positive effects of yellow light on microbial activity. Additionally, despite the sluggish denitrification aroused by blue light, negligible cellular damage was observed. Antioxidant capability divergence, microbial community shifting and metabolic flux redirection contributed to the wavelength-dependent effects. Halomonas and Pseudomonas were identified as high-credit taxonomic biomarkers of yellow and blue light. As revealed by metabolomics, pantothenate and CoA biosynthesis, glutamate metabolism and alkaloid biosynthesis presented high impact values. Co-analysis of metabolomics and metagenomics based on microbial topology further distinguished pivotal metabolic pathways and genes. Oxidative phosphorylation contributed to the divergent denitrification performance through electron transfer chains, whereas glutamate and glutathione metabolism contributed to oxidative stress alleviation and mediated the metabolic flux between peroxisome and nitrogen metabolism. This study shed a light on the application of optical strategy to regulate denitrification performance and achieve either complete denitrification or PD/A.PMID:36746030 | DOI:10.1016/j.watres.2022.119434

EBioMedicine. 2023 Feb 4;89:104456. doi: 10.1016/j.ebiom.2023.104456. Online ahead of print.ABSTRACTA major evolution from purely clinical diagnoses to biomarker supported clinical diagnosing has been occurring over the past years in neurology. High-throughput methods, such as next-generation sequencing and mass spectrometry-based proteomics along with improved neuroimaging methods, are accelerating this development. This calls for a consensus framework that is broadly applicable and provides a spot-on overview of the clinical validity of novel biomarkers. We propose a harmonized terminology and a uniform concept that stratifies biomarkers according to clinical context of use and evidence levels, adapted from existing frameworks in oncology with a strong focus on (epi)genetic markers and treatment context. We demonstrate that this framework allows for a consistent assessment of clinical validity across disease entities and that sufficient evidence for many clinical applications of protein biomarkers is lacking. Our framework may help to identify promising biomarker candidates and classify their applications by clinical context, aiming for routine clinical use of (protein) biomarkers in neurology.PMID:36745974 | DOI:10.1016/j.ebiom.2023.104456

PLoS One. 2023 Feb 6;18(2):e0281218. doi: 10.1371/journal.pone.0281218. eCollection 2023.ABSTRACTINTRODUCTION: Breast cancer is the most common cancer worldwide and the leading cause of cancer related deaths among women. The high incidence and mortality of breast cancer calls for improved prevention, diagnostics, and treatment, including identification of new prognostic and predictive biomarkers for use in precision medicine.MATERIAL AND METHODS: With the aim of compiling a cohort amenable to integrative study designs, we collected detailed epidemiological and clinical data, blood samples, and tumor tissue from a subset of participants from the prospective, population-based Norwegian Women and Cancer (NOWAC) study. These study participants were diagnosed with invasive breast cancer in North Norway before 2013 according to the Cancer Registry of Norway and constitute the Clinical and Multi-omic (CAMO) cohort. Prospectively collected questionnaire data on lifestyle and reproductive factors and blood samples were extracted from the NOWAC study, clinical and histopathological data were manually curated from medical records, and archived tumor tissue collected.RESULTS: The lifestyle and reproductive characteristics of the study participants in the CAMO cohort (n = 388) were largely similar to those of the breast cancer patients in NOWAC (n = 10 356). The majority of the cancers in the CAMO cohort were tumor grade 2 and of the luminal A subtype. Approx. 80% were estrogen receptor positive, 13% were HER2 positive, and 12% were triple negative breast cancers. Lymph node metastases were present in 31% at diagnosis. The epidemiological dataset in the CAMO cohort is complemented by mRNA, miRNA, and metabolomics analyses in plasma, as well as miRNA profiling in tumor tissue. Additionally, histological analyses at the level of proteins and miRNAs in tumor tissue are currently ongoing.CONCLUSION: The CAMO cohort provides data suitable for epidemiological, clinical, molecular, and multi-omics investigations, thereby enabling a systems epidemiology approach to translational breast cancer research.PMID:36745618 | DOI:10.1371/journal.pone.0281218

PLoS One. 2023 Feb 6;18(2):e0280777. doi: 10.1371/journal.pone.0280777. eCollection 2023.ABSTRACTTri-Butyl Tin (TBT) remains as a legacy pollutant in the benthic environments. Although the toxic impacts and endocrine disruption caused by TBT to gastropod molluscs have been established, the changes in energy reserves allocated to maintenance, growth, reproduction and survival of European oysters Ostrea edulis, a target species of concerted benthic habitat restoration projects, have not been explored. This study was designed to evaluate the effect of TBT chloride (TBTCl) on potential ions and relevant metabolomic pathways and its association with changes in physiological, biochemical and reproductive parameters in O. edulis exposed to environmental relevant concentrations of TBTCl. Oysters were exposed to TBTCl 20 ng/L (n = 30), 200 ng/L (n = 30) and 2000 ng/L (n = 30) for nine weeks. At the end of the exposure, gametogenic stage, sex, energy reserve content and metabolomic profiling analysis were conducted to elucidate the metabolic alterations that occur in individuals exposed to those compounds. Metabolite analysis showed significant changes in the digestive gland biochemistry in oysters exposed to TBTCl, decreasing tissue ATP concentrations through a combination of the disruption of the TCA cycle and other important molecular pathways involved in homeostasis, mitochondrial metabolism and antioxidant response. TBTCl exposure increased mortality and caused changes in the gametogenesis with cycle arrest in stages G0 and G1. Sex determination was affected by TBTCl exposure, increasing the proportion of oysters identified as males in O. edulis treated at 20ng/l TBTCl, and with an increased proportion of inactive stages in oysters treated with 2000 ng/l TBTCl. The presence and persistence of environmental pollutants, such as TBT, could represent an additional threat to the declining O. edulis populations and related taxa around the world, by increasing mortality, changing reproductive maturation, and disrupting metabolism. Our findings identify the need to consider additional factors (e.g. legacy pollution) when identifying coastal locations for shellfish restoration.PMID:36745593 | DOI:10.1371/journal.pone.0280777

Food Funct. 2023 Feb 6. doi: 10.1039/d2fo03215e. Online ahead of print.ABSTRACTWhile formulating a probiotic food, it is mandatory to make sure that the viability of probiotics is adequate at the point of consumption, which can be strongly compromised by stressful conditions due to low pH and high osmolarity. In this study, three probiotic lactobacilli were subjected to different pre-adaptation conditions, and the turbidimetric growth kinetics in challenging conditions (pH 4.0-6.5, NaCl 1-7%, sucrose 0.1-0.7 M) were evaluated. Different effects were observed for Lactobacillus acidophilus, Lacticaseibacillus casei, and Lactiplantibacillus plantarum. Indeed, pre-exposition to sub-optimal conditions in terms of pH and % NaCl significantly improved the ability of L. acidophilus and L. casei to overcome the osmotic stress due to salt or sucrose, and similar effects were observed for acidic stress. L. plantarum showed to be more tolerant to the challenging conditions applied in this study. Anyway, the pre-adaptation at conditions SUB_1 (pH 4.5 and NaCl 4%) and SUB_2 (pH 5 and NaCl 2%) speeded-up its growth kinetics by reducing the length of the lag phase under sucrose stress and enhancing the maximum growth rate at the highest pH tested. Moreover, an improvement in biomass amount was observed under sucrose stress. The whole data evidenced that the application of the appropriate pre-adaptation condition could contribute to making probiotics more robust towards challenging conditions due to food matrix, processing, and storage as well as gastrointestinal transit. Further studies will be necessary to gain insight into the proteomics and metabolomics responsible for increased tolerance to stressful conditions.PMID:36745384 | DOI:10.1039/d2fo03215e

Metabolomics. 2023 Feb 6;19(2):11. doi: 10.1007/s11306-023-01974-3.ABSTRACTBACKGROUND: Liquid chromatography-high resolution mass spectrometry (LC-HRMS) is a popular approach for metabolomics data acquisition and requires many data processing software tools. The FAIR Principles - Findability, Accessibility, Interoperability, and Reusability - were proposed to promote open science and reusable data management, and to maximize the benefit obtained from contemporary and formal scholarly digital publishing. More recently, the FAIR principles were extended to include Research Software (FAIR4RS).AIM OF REVIEW: This study facilitates open science in metabolomics by providing an implementation solution for adopting FAIR4RS in the LC-HRMS metabolomics data processing software. We believe our evaluation guidelines and results can help improve the FAIRness of research software.KEY SCIENTIFIC CONCEPTS OF REVIEW: We evaluated 124 LC-HRMS metabolomics data processing software obtained from a systematic review and selected 61 software for detailed evaluation using FAIR4RS-related criteria, which were extracted from the literature along with internal discussions. We assigned each criterion one or more FAIR4RS categories through discussion. The minimum, median, and maximum percentages of criteria fulfillment of software were 21.6%, 47.7%, and 71.8%. Statistical analysis revealed no significant improvement in FAIRness over time. We identified four criteria covering multiple FAIR4RS categories but had a low %fulfillment: (1) No software had semantic annotation of key information; (2) only 6.3% of evaluated software were registered to Zenodo and received DOIs; (3) only 14.5% of selected software had official software containerization or virtual machine; (4) only 16.7% of evaluated software had a fully documented functions in code. According to the results, we discussed improvement strategies and future directions.PMID:36745241 | DOI:10.1007/s11306-023-01974-3

Metabolomics. 2023 Feb 6;19(2):10. doi: 10.1007/s11306-022-01969-6.ABSTRACTINTRODUCTION: The primate retina has evolved regional specialisations for specific visual functions. The macula is specialised towards high acuity vision and is an area that contains an increased density of cone photoreceptors and signal processing neurons. Different regions in the retina display unique susceptibility to pathology, with many retinal diseases primarily affecting the macula.OBJECTIVES: To better understand the properties of different retinal areas we studied the differential distribution of metabolites across the retina.METHODS: We conducted an untargeted metabolomics analysis on full-thickness punches from three different regions (macula, temporal peri-macula and periphery) of healthy primate retina.RESULTS: Nearly half of all metabolites identified showed differential abundance in at least one comparison between the three regions. Furthermore, mapping metabolomics results from macula-specific eye diseases onto our region-specific metabolite distributions revealed differential abundance defining systemic metabolic dysregulations that were region specific.CONCLUSIONS: The unique metabolic phenotype of different retinal regions is likely due to the differential distribution of different cell types in these regions reflecting the specific metabolic requirements of each cell type. Our results may help to better understand the pathobiology of retinal diseases with region specificity.PMID:36745234 | DOI:10.1007/s11306-022-01969-6

J Agric Food Chem. 2023 Feb 6. doi: 10.1021/acs.jafc.2c04344. Online ahead of print.ABSTRACTAcute lung injury (ALI) is the main cause of death for the elderly and children due to its high morbidity and mortality rates. Plant-derived functional foods are becoming increasingly important to the healthcare and food industries for adjunctive and alternative treatments of ALI. Polyphenols have been regarded to be beneficial to the prevention and amelioration of ALI. Rosa roxburghii Tratt fruit polyphenols (RRTP) has potential to prevent ALI, but mechanism remains unclear. This study was set up to systematically analyze the RRTP extract active ingredients, comprehensively evaluate its protective effects via lung histopathological examination, protein concentration, and cytokines production in ALI mice induced by lipopolysaccharide (LPS), and finally revealed alleviation mechanisms of the regulatory effects of RRTP by proteomics and metabolomics approach. The results demonstrated RRTP could synergistically exert significant preventive effects against ALI by notably ameliorating lung histopathological damage and pulmonary capillary permeability in ALI mice, inhibiting lung tissue inflammatory response and acute phase proteins and S-100 calcium binding proteins, suppressing excessive activation of complement and coagulation cascades, and regulating disordered lipids metabolism and amino acid metabolism. This study illustrated that RRTP has obvious advantages in ALI adjunctive therapy and revealed the complicated amelioration mechanisms, which provides a breakthrough for the development and demonstration of RRTP as a nutritional compound additive for complementary therapy of ALI.PMID:36745194 | DOI:10.1021/acs.jafc.2c04344

Expert Rev Proteomics. 2023 Feb 6. doi: 10.1080/14789450.2023.2176754. Online ahead of print.NO ABSTRACTPMID:36744392 | DOI:10.1080/14789450.2023.2176754

Cancer Discov. 2023 Feb 6;13(2):266-268. doi: 10.1158/2159-8290.CD-22-1325.ABSTRACTIn this issue of Cancer Discovery, Thomas and colleagues leverage mass spectrometry metabolomics, stable isotope labeling, and functional studies to explore metabolic vulnerabilities in cancers harboring mutations in isocitrate dehydrogenase (IDH). The authors present compelling data to support the claim that dysregulated lipid synthesis underpins a synthetic lethal target in cancers with IDH1, but not IDH2, mutations. See related article by Thomas et al., p. 496 (9).PMID:36744320 | DOI:10.1158/2159-8290.CD-22-1325

Front Pharmacol. 2023 Jan 20;14:1096159. doi: 10.3389/fphar.2023.1096159. eCollection 2023.ABSTRACTObjectives: This study involved a multi-omics analysis of glioblastoma (GBM) samples to elaborate the potential mechanism of drug treatment. Methods: The GBM cells treated with or without orexin A were acquired from sequencing analysis. Differentially expressed genes/proteins/metabolites (DEGs/ DEPs/ DEMs) were screened. Next, combination analyses were conducted to investigate the common pathways and correlations between the two groups. Lastly, transcriptome-proteome-metabolome association analysis was carried out to determine the common pathways, and the genes in these pathways were analyzed through Kaplan-Meier (K-M) survival analysis in public databases. Cell and animal experiments were performed to investigate the anti-glioma activity of orexin A. Results: A total of 1,527 DEGs, 52 DEPs, and 153 DEMs were found. Moreover, the combination analyses revealed that 6, 4, and 1 common pathways were present in the transcriptome-proteome, proteome-metabolome, and transcriptome-metabolome, respectively. Certain correlations were observed between the two data sets. Finally, 11 common pathways were discovered in association analysis, and 138 common genes were screened out in these common pathways. Six genes showed significant differences in terms of survival in both TCGA and CGGA. In addition, orexin A inhibited the proliferation, migration, and invasion of glioma in vitro and in vivo. Conclusion: Eleven common KEGG pathways with six common genes were found among different omics participations, revealing the underlying mechanisms in different omics and providing theoretical basis and reference for multi-omics research on drug treatment.PMID:36744263 | PMC:PMC9894894 | DOI:10.3389/fphar.2023.1096159