PubMed

Environ Int. 2023 Apr 20;175:107942. doi: 10.1016/j.envint.2023.107942. Online ahead of print.ABSTRACTBisphenol analogs (BPs) are widely used as industrial alternatives for Bisphenol A (BPA). Their toxicity assessment in humans has mainly focused on estrogenic activity, while other toxicity effects and mechanisms resulting from BPs exposure remain unclear. In this study, we investigated the effects of three BPs (Bisphenol AF (BPAF), Bisphenol G (BPG) and Bisphenol PH (BPPH)) on metabolic pathways of HepG2 cells. Results from comprehensive cellular bioenergetics analysis and nontarget metabolomics indicated that the most important process affected by BPs exposure was energy metabolism, as evidenced by reduced mitochondrial function and enhanced glycolysis. Compared to the control group, BPG and BPPH exhibited a consistent pattern of metabolic dysregulation, while BPAF differed from both, such as an increased ATP: ADP ratio (1.29-fold, p < 0.05) observed in BPAF and significantly decreased ATP: ADP ratio for BPG (0.28-fold, p < 0.001) and BPPH (0.45-fold, p < 0.001). Bioassay endpoint analysis revealed BPG/BPPH induced alterations in mitochondrial membrane potential and overproductions of reactive oxygen species. Taken together these data suggested that BPG/BPPH induced oxidative stress and mitochondrial damage in cells results in energy metabolism dysregulation. By contrast, BPAF had no effect on mitochondrial health, but induced a proliferation promoting effect on cells, which might contribute to the energy metabolism dysfunction. Interestingly, BPPH induced the greatest mitochondrial damage among the three BPs but did not exhibit Estrogen receptor alpha (ERα) activating effects. This study characterized the distinct metabolic mechanisms underlying energy metabolism dysregulation induced by different BPs in target human cells, providing new insight into the evaluation of the emerging BPA substitutes.PMID:37094511 | DOI:10.1016/j.envint.2023.107942

Sci Total Environ. 2023 Apr 20:163592. doi: 10.1016/j.scitotenv.2023.163592. Online ahead of print.ABSTRACTEpidemiological and experimental data have associated exposure to fine particulate matter (PM2.5) with various metabolic dysfunctions and diseases, including overweight and type 2 diabetes. Adipose tissue is an energy pool for storing lipids, a necessary regulator of glucose homeostasis, and an active endocrine organ, playing an essential role in developing various related diseases such as diabetes and obesity. However, the molecular mechanisms underlying PM2.5-impaired functions in adipose tissue have rarely been explored. In this work, metabolomics based on liquid chromatography-mass spectrometry was performed to study the adverse impacts of PM2.5 exposure on brown adipose tissue (BAT) and white adipose tissue (WAT) in the diabetic mouse model. We found the effects of PM2.5 exposure by comparing the different metabolites in both adipose tissues of male db/db mice using real-ambient PM2.5 exposure. The results showed that PM2.5 exposure changed the purine metabolism in mice, especially the dramatic increase of xanthine content in both WAT and BAT. These changes led to significant oxidative stress. Then the results from real-time quantitative polymerase chain reaction showed that PM2.5 exposure could cause the production of inflammatory factors in both adipose tissues. Moreover, the increased reactive oxygen species (ROS) promoted triglyceride accumulation in WAT and inhibited its decomposition, causing increased WAT content in db/db mice. In addition, PM2.5 exposure significantly suppressed thermogenesis and affected energy metabolism in the BAT of male db/db mice, which may deteriorate insulin sensitivity and blood glucose regulation. This research demonstrated the impact of PM2.5 on the adipose tissue of male db/db mice, which may be necessary for public health.PMID:37087002 | DOI:10.1016/j.scitotenv.2023.163592

J Ethnopharmacol. 2023 Apr 20:116529. doi: 10.1016/j.jep.2023.116529. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The Suxiao Jiuxin pill (SJP) is a Chinese medical patent drug on the national essential drug list of China, with well-established cardiovascular protective effects in the clinic. However, the mechanisms underlying the protective effects of SJP on cardiovascular disease have not yet been elucidated clearly, especially its relationship with the gut microbiota.AIM OF THE STUDY: This study aimed to investigate the cardioprotective effect of SJP against isoproterenol-induced acute myocardial infarction (AMI) by integrating the gut microbiome and metabolome.METHODS: A rat model of AMI was generated using isoproterenol. Firstly, the effect of antibiotic (ABX) treatment on the blood absorption and excretion of the main components of SJP were studied. Secondly, 16S rRNA sequencing and untargeted metabolomics were used to discover the improvement of SJP treatment on gut microbiota and host metabolism in AMI rats. Finally, targeted metabolomics was used to verify the effects of SJP treatment on host metabolism in AMI rats.RESULT: The results showed that ABX treatment could affect the blood absorption and fecal excretion of the main active components of SJP. At the same time, SJP can restore the richness and diversity of gut microbiota, and multiple gut microbiota (including Jeotgalicoccus, Lachnospiraceae, and Blautia) are significantly associated with fatty acids. Untargeted metabolomics also found that SJP could restore the levels of various fatty acid metabolites in serum and cecal contents (p < 0.01, FC > 1.5 and VIP >1). Targeted metabolomics further confirmed that 41, 21, and 39 fatty acids were significantly altered in serum, cecal contents, and heart samples, respectively. Interestingly, these fatty acids belong to the class of eicosanoids, and SJP can significantly downregulate these eicosanoids in AMI rats.CONCLUSION: The results of this study suggest that SJP may exert its cardioprotective effects by remodeling the gut microbiota and host fatty acid metabolism.PMID:37086873 | DOI:10.1016/j.jep.2023.116529

BMC Plant Biol. 2023 Apr 20;23(1):207. doi: 10.1186/s12870-023-04222-x.ABSTRACTBACKGROUND: Asparagus officinalis L. is a worldwide cultivated vegetable enrichened in both nutrient and steroidal saponins with multiple pharmacological activities. The upstream biosynthetic pathway of steroidal saponins (USSP) for cholesterol (CHOL) synthesis has been studied, while the downstream pathway of steroidal saponins (DSSP) starting from cholesterol and its regulation in asparagus remains unknown.RESULTS: Metabolomics, Illumina RNAseq, and PacBio IsoSeq strategies were applied to different organs of both cultivated green and purple asparagus to detect the steroidal metabolite profiles & contents and to screen their key genes for biosynthesis and regulation. The results showed that there is a total of 427 compounds, among which 18 steroids were detected with fluctuated concentrations in roots, spears and flowering twigs of two garden asparagus cultivars. The key genes of DSSP include; steroid-16-hydroxylase (S16H), steroid-22-hydroxylase (S22H) and steroid-22-oxidase-16-hydroxylase (S22O-16H), steroid-26-hydroxylase (S26H), steroid-3-β-glycosyltransferase (S3βGT) and furostanol glycoside 26-O-beta-glucosidases (F26GHs) which were correlated with the contents of major steroidal saponins were screened, and the transcriptional factors (TFs) co-expressing with the resulted from synthetic key genes, including zinc fingers (ZFs), MYBs and WRKYs family genes were also screened.CONCLUSIONS: Based on the detected steroidal chemical structures, profiles and contents which correlated to the expressions of screened synthetic and TFs genes, the full steroidal saponin synthetic pathway (SSP) of asparagus, including its key regulation networks was proposed for the first time.PMID:37081391 | DOI:10.1186/s12870-023-04222-x

Inflamm Res. 2023 Apr 20. doi: 10.1007/s00011-023-01732-0. Online ahead of print.ABSTRACTBACKGROUND: Lipids, significant signaling molecules, regulate a multitude of cellular responses and biological pathways in asthma which are closely associated with disease onset and progression. However, the characteristic lipid genes and metabolites in asthma remain to be explored. It is also necessary to further investigate the role of lipid molecules in asthma based on high-throughput data.OBJECTIVE: To explore the biomarkers and molecular mechanisms associated with lipid metabolism in asthma.METHODS: In this study, we selected three mouse-derived datasets and one human dataset (GSE41665, GSE41667, GSE3184 and GSE67472) from the GEO database. Five machine learning algorithms, LASSO, SVM-RFE, Boruta, XGBoost and RF, were used to identify core gene. Additionally, we used non-negative matrix breakdown (NMF) clustering to identify two lipid molecular subgroups and constructed a lipid metabolism score by principal component analysis (PCA) to differentiate the subtypes. Finally, Western blot confirmed the altered expression levels of core genes in OVA (ovalbumin) and HDM+LPS (house dust mite+lipopolysaccharide) stimulated and challenged BALB/c mice, respectively. Results of non-targeted metabolomics revealed multiple differentially expressed metabolites in the plasma of OVA-induced asthmatic mice.RESULTS: Cholesterol 25-hydroxylase (CH25H) was finally localized as a core lipid metabolism gene in asthma and was verified to be highly expressed in two mouse models of asthma. Five-gene lipid metabolism constructed from CYP2E1, CH25H, PTGES, ALOX15 and ME1 was able to distinguish the subtypes effectively. The results of non-targeted metabolomics showed that most of the aberrantly expressed metabolites in the plasma of asthmatic mice were lipids, such as LPC 16:0, LPC 18:1 and LPA 18:1.CONCLUSION: Our findings imply that the lipid-related gene CH25H may be a useful biomarker in the diagnosis of asthma.PMID:37081162 | DOI:10.1007/s00011-023-01732-0

Sci Rep. 2023 Apr 20;13(1):6497. doi: 10.1038/s41598-023-33682-2.ABSTRACTCoronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is highly heterogeneous, ranging from asymptomatic to severe and fatal cases. COVID-19 has been characterized by an increase of serum pro-inflammatory cytokine levels which seems to be associated with fatal cases. By contrast, the role of pro-resolving lipid mediators (SPMs), involved in the attenuation of inflammatory responses, has been scarcely investigated, so further studies are needed to understand SPMs metabolism in COVID-19 and other infectious diseases. Our aim was to analyse the lipid mediator metabolome, quantifying pro- and anti-inflammatory serum bioactive lipids by LC-MS/MS in 7 non-infected subjects and 24 COVID-19 patients divided into mild, moderate, and severe groups according to the pulmonary involvement, to better understand the disease outcome and the severity of the pulmonary manifestations. Statistical analysis was performed with the R programming language (R Foundation for Statistical Computing, Vienna, Austria). All COVID-19 patients had increased levels of Prostaglandin E2. Severe patients showed a significant increase versus controls, mild- and moderate-affected patients, expressed as median (interquartile range), in resolvin E1 [112.6 (502.7) vs 0.0 (0.0) pg/ml in the other groups], as well as in maresin 2 [14.5 (7.0) vs 8.1 (4.2), 5.5 (4.3), and 3.0 (4.0) pg/ml, respectively]. Moreover, 14-hydroxy docosahexaenoic acid (14-HDHA) levels were also increased in severe vs control and mild-affected patients [24.7 (38.2) vs 2.4 (2.2) and 3.7 (6.4) ng/mL, respectively]. Resolvin D5 was also significantly elevated in both moderate [15.0 (22.4) pg/ml] and severe patients [24.0 (24.1) pg/ml] versus controls [0.0 (0.0) pg/ml]. These results were confirmed by sparse partial least squares discriminant analysis which highlighted the contribution of these mediators to the separation between each of the groups. In conclusion, the potent inflammatory response to SARS-CoV-2 infection involves not only pro- but also anti-inflammatory lipid mediators that can be quantified in easily accessible serum samples, suggesting the need to perform future research on their generation pathways that will help us to discover new therapeutic targets.PMID:37081104 | DOI:10.1038/s41598-023-33682-2

Sci Rep. 2023 Apr 20;13(1):6492. doi: 10.1038/s41598-023-33059-5.ABSTRACTWe aimed to identify the immune and Toll-like receptor (TLR) signaling pathway related feature lncRNAs to construct the diagnostic nomograms for acute ischemic stroke (AIS). Two AIS-associated expression profiles GSE16561 and GSE22255 were downloaded from NCBI Gene Expression Omnibus, the former was the training set and the latter was the validation set. The differential expression genes (DEGs) and lncRNAs (DElncRNAs) related to TLR signaling pathway were identified between AIS and control groups. The single sample gene set enrichment analysis (ssGSEA) was applied to evaluate the immune infiltration. The immune and TLR signaling pathway related DElncRNAs were determined. Three optimization algorithms were utilized to select the immune and TLR signaling pathway related feature lncRNAs to construct the diagnostic nomograms of AIS. Based on the lncRNA signature, a ceRNA network was constructed. 37 DEGs and 28 DElncRNAs related to TLR signaling pathway were identified in GSE16561. 16 immune cell types exhibited significant differences in distribution between AIS and control groups. 28 immune and TLR signaling pathway related DElncRNAs were determined. 8 immune and TLR signaling pathway related feature lncRNAs were selected. The diagnostic nomograms of AIS performed well in both datasets. A ceRNA network was constructed consisting of 7 immune and TLR signaling pathway related feature lncRNAs as well as 19 AIS related miRNAs and 21 TLR signaling pathway related genes. LINC00173, LINC01089, LINC02210, MIR600HG, SNHG14, TP73-AS1, LINC00680 and CASC2 may be the potential biomarkers of AIS diagnosis, and TLR signaling pathway may be a promising immune related therapeutic target for AIS.PMID:37081063 | DOI:10.1038/s41598-023-33059-5

NPJ Biofilms Microbiomes. 2023 Apr 20;9(1):20. doi: 10.1038/s41522-023-00387-3.ABSTRACTThere have been many reports on the genetic mechanism in rhesus macaques (RMs) for environmental adaptation to high altitudes, but the synergistic involvement of gut microbiota in this adaptation remains unclear. Here we performed fecal metagenomic and metabolomic studies on samples from high- and low-altitude populations to assess the synergistic role of gut microbiota in the adaptation of RMs to high-altitude environments. Microbiota taxonomic annotation yielded 7471 microbiota species. There were 37 bacterial species whose abundance was significantly enriched in the high-altitude populations, 16 of which were previously reported to be related to the host's dietary digestion and energy metabolism. Further functional gene enrichment found a stronger potential for gut microbiota to synthesize energy substrate acetyl-CoA using CO2 and energy substrate pyruvate using oxaloacetate, as well as a stronger potential to transform acetyl-CoA to energy substrate acetate in high-altitude populations. Interestingly, there were no apparent differences between low-altitude and high-altitude populations in terms of genes enriched in the main pathways by which the microbiota consumed the three energy substrates, and none of the three energy substrates were detected in the fecal metabolites. These results strongly suggest that gut microbiota plays an important energy compensatory role that helps RMs to adapt to high-altitude environments. Further functional enrichment after metabolite source analysis indicated the abundance of metabolites related to the degradation of exogenous toxins was also significantly higher in high-altitude populations, which suggested a contributory role of gut microbiota to the degradation of exogenous toxins in wild RMs adapted to high-altitude environments.PMID:37081021 | DOI:10.1038/s41522-023-00387-3

Biomed Chromatogr. 2023 Apr 20:e5658. doi: 10.1002/bmc.5658. Online ahead of print.ABSTRACTBACKGROUND: Colon cancer (CC) is a malignancy of the digestive tract, and CT-guided radiofrequency ablation (CT-guided RFA) has been extensively adopted in cancer treatment. We aimed to explore the changes of fecal metabolism after CT-guided RFA in CC mice.METHODS: The orthotopic CC mice received CT-guided RFA upon modeling. Subsequently, we quantified tumor volumes and weights to assess treatment efficacy. Next, because metabolomics is useful for evaluating therapeutic validity, feces were collected for metabolomics analysis.RESULTS: CT-guided RFA inhibited tumor growth effectively. Additionally, metabolomics results showed that the contents of bile acids and fatty acids downregulated in CC mouse feces. Moreover, the levels of amino acids and carbohydrates were decreased while the levels of fatty acids, organic acids, phenols, pyridines and short-chain fatty acids were elevated in feces after CC mouse receiving CT-guided RFA. Pathway enrichment analysis revealed those differential metabolites were closely related to fatty acids degradation and synthesis.CONCLUSION: CT-guided RFA possesses a strong ability to suppress CC development in mice, accompanied by a significant increase of fatty acid content in feces. This study proposes a novel approach and target for CC treatment, which provides hope for CC patients and establishes a solid basis for future in-depth studies.PMID:37080899 | DOI:10.1002/bmc.5658

ACS Appl Bio Mater. 2023 Apr 20. doi: 10.1021/acsabm.3c00111. Online ahead of print.ABSTRACTPhotothermal therapy has developed into an important field of tumor treatment research, and numerous studies have focused on the preparation of photothermal therapeutic agents, tumor targeting, diagnosis, and treatment integration. However, there are few studies on the mechanism of photothermal therapy acting on cancer cells. Here we investigated the metabolomics of lung cancer cell A549 during gold nanorod (GNR) photothermal treatment by high-resolution LC/MS, and several differential metabolites and corresponding metabolic pathways during photothermal therapy were found. The main differential metabolites contained 18-hydroxyoleate, beta-alanopine and cis-9,10-epoxystearic acid, and phosphorylcholine. Pathway analysis also showed metabolic changes involving cutin, suberine, and wax biosynthesis, pyruvate and glutamic acid synthesis, and choline metabolism. Analysis also showed that the photothermal process of GNRs may induce cytotoxicity by affecting pyruvate and glutamate synthesis, normal choline metabolism, and ultimately apoptosis.PMID:37079717 | DOI:10.1021/acsabm.3c00111

PLoS One. 2023 Apr 20;18(4):e0284599. doi: 10.1371/journal.pone.0284599. eCollection 2023.ABSTRACTTesting the composition, quality and authenticity of edible oils is crucial to safeguard the consumers' rights and health. The aim of our study was to identify oil-specific markers to enable the differentiation and authentication of sunflower, sesame, flaxseed and rapeseed oils, and to evaluate their antioxidant activity, total phenolic and carotenoid content. A metabolomic approach based on liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry was employed for marker discovery. Spectrophotometric method was used for determination of antioxidant activity, total phenolic and carotenoid content. 76 oil samples from the four different manufacturers were examined. We identified 13 oil-specific markers for sunflower seed oil, 8 for rapeseed oil, 5 for sesame seed oil and 3 for flaxseed oil, their retention times, accurate masses, and characteristic fragment ions are reported. The abundances of the markers for each plant species were found to vary depending on the oil producer and the product batch. Significant differences in antioxidant activity, total phenolic and carotenoid content were also observed both between oils and within oil type. The highest total phenolic content (84.03 ± 4.19 to 103.79 ± 3.67 mg of gallic acid/kg) and antioxidant activity (245.67 ± 7.59 to 297.22 ± 2.32 mg Trolox/kg) were found in sesame seed and flaxseed oils, respectively. Identified metabolic markers can be used as qualitative markers to confirm the authenticity or to detect adulterations of oils. Composition, properties and authenticity testing should be more rigorous for food products marketed as health-promoting.PMID:37079607 | DOI:10.1371/journal.pone.0284599

Metabolomics. 2023 Apr 20;19(5):44. doi: 10.1007/s11306-023-02010-0.ABSTRACTINTRODUCTION AND OBJECTIVES: Multiple sclerosis (MS) is a disease of the central nervous system associated with immune dysfunction, demyelination, and neurodegeneration. The disease has heterogeneous clinical phenotypes such as relapsing-remitting MS (RRMS) and progressive multiple sclerosis (PMS), each with unique pathogenesis. Metabolomics research has shown promise in understanding the etiologies of MS disease. However, there is a paucity of clinical studies with follow-up metabolomics analyses. This 5-year follow-up (5YFU) cohort study aimed to investigate the metabolomics alterations over time between different courses of MS patients and healthy controls and provide insights into metabolic and physiological mechanisms of MS disease progression.METHODS: A cohort containing 108 MS patients (37 PMS and 71 RRMS) and 42 controls were followed up for a median of 5 years. Liquid chromatography-mass spectrometry (LC-MS) was applied for untargeted metabolomics profiling of serum samples of the cohort at both baseline and 5YFU. Univariate analyses with mixed-effect ANCOVA models, clustering, and pathway enrichment analyses were performed to identify patterns of metabolites and pathway changes across the time effects and patient groups.RESULTS AND CONCLUSIONS: Out of 592 identified metabolites, the PMS group exhibited the most changes, with 219 (37%) metabolites changed over time and 132 (22%) changed within the RRMS group (Bonferroni adjusted P < 0.05). Compared to the baseline, there were more significant metabolite differences detected between PMS and RRMS classes at 5YFU. Pathway enrichment analysis detected seven pathways perturbed significantly during 5YFU in MS groups compared to controls. PMS showed more pathway changes compared to the RRMS group.PMID:37079261 | DOI:10.1007/s11306-023-02010-0

Blood Cancer Discov. 2023 Apr 20:OF1-OF4. doi: 10.1158/2643-3230.BCD-22-0213. Online ahead of print.ABSTRACTIn patients with multiple myeloma, completion of mRNA-based vaccination schemes failed to yield detectable SARS-CoV-2 Omicron-neutralizing antibodies and S1-RBD-specific CD8+ T cells in approximately 60% and 80% of the cases, respectively. Patients who develop breakthrough infections exhibited very low levels of live-virus neutralizing antibodies and the absence of follicular T helper cells. See related article by Azeem et al., (9) . See related article by Chang et al., (10) .PMID:37078891 | DOI:10.1158/2643-3230.BCD-22-0213

Anal Chem. 2023 Apr 20. doi: 10.1021/acs.analchem.2c05728. Online ahead of print.ABSTRACTMass spectrometry (MS) has become a powerful tool for metabolome, lipidome, and proteome analyses. The efficient analysis of multi-omics in single cells, however, is still challenging in the manipulation of single cells and lack of in-fly cellular digestion and extraction approaches. Here, we present a streamlined strategy for highly efficient and automatic single-cell multi-omics analysis by MS. We developed a 10-pL-level microwell chip for housing individual single cells, whose proteins were found to be digested in 5 min, which is 144 times shorter than traditional bulk digestion. Besides, an automated picoliter extraction system was developed for sampling of metabolites, phospholipids, and proteins in tandem from the same single cell. Also, 2 min MS2 spectra were obtained from 700 pL solution of a single cell sample. In addition, 1391 proteins, phospholipids, and metabolites were detected from one single cell within 10 min. We further analyzed cells digested from cancer tissue samples, achieving up to 40% increase in cell classification accuracy using multi-omics analysis in comparison with single-omics analysis. This automated single-cell MS strategy is highly efficient in analyzing multi-omics information for investigation of cell heterogeneity and phenotyping for biomedical applications.PMID:37078759 | DOI:10.1021/acs.analchem.2c05728

Aging Cell. 2023 Apr 20:e13849. doi: 10.1111/acel.13849. Online ahead of print.ABSTRACTDecline in neuromuscular function with aging is known to be a major determinant of disability and all-cause mortality in late life. Despite the importance of the problem, the neurobiology of age-associated muscle weakness is poorly understood. In a previous report, we performed untargeted metabolomics on frail older adults and discovered prominent alteration in the kynurenine pathway, the major route of dietary tryptophan degradation that produces neurotoxic intermediate metabolites. We also showed that neurotoxic kynurenine pathway metabolites are correlated with increased frailty score. For the present study, we sought to further examine the neurobiology of these neurotoxic intermediates by utilizing a mouse model that has a deletion of the quinolinate phosphoribosyltransferase (QPRT) gene, a rate-limiting step of the kynurenine pathway. QPRT-/- mice have elevated neurotoxic quinolinic acid level in the nervous system throughout their lifespan. We found that QPRT-/- mice have accelerated declines in neuromuscular function in an age- and sex-specific manner compared to control strains. In addition, the QPRT-/- mice show premature signs of frailty and body composition changes that are typical for metabolic syndrome. Our findings suggest that the kynurenine pathway may play an important role in frailty and age-associated muscle weakness.PMID:37078472 | DOI:10.1111/acel.13849

Food Funct. 2023 Apr 20. doi: 10.1039/d3fo00775h. Online ahead of print.ABSTRACTOsteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degeneration, subchondral bone sclerosis, synovial hyperplasia and inflammation as the main pathological manifestations. This study aims to investigate the protective effect of prebiotics in post-traumatic osteoarthritic (PTOA) mice by modulating the gut barrier and fecal metabolomics. The results suggested that cartilage degeneration, osteophyte formation and inflammation were significantly reduced by prebiotics in PTOA mice. In addition, the gut barrier was protected by the increased expression of tight junction proteins ZO-1 and occludin in the colon. High-throughput sequencing found that 220 fecal metabolites were affected by joint trauma, 81 of which were significantly recovered after probiotic intervention, and some metabolites (valerylcarnitine, adrenic acid, oxoglutaric acid, etc.) were closely associated with PTOA. Our study demonstrates that prebiotics can delay the progression of PTOA by regulating the metabolites of the gut microbiota and protecting the gut barrier, which is expected to be an intervention method for PTOA.PMID:37077156 | DOI:10.1039/d3fo00775h

J Affect Disord. 2023 Apr 19:S0165-0327(23)00501-3. doi: 10.1016/j.jad.2023.04.039. Online ahead of print.ABSTRACTBACKGROUND: Light is a known factor affecting mood and the circadian system. Light deficit is linked to deteriorated transduction of photic information to the brain, and reduced amplitude of the perceived circadian light signaling. Retinal ganglion cells (RGCs) loss due to advanced glaucoma can be a factor compromising light perception, with consequences for circadian rhythms, sleep and mood. This study aimed to estimate associations of RGCs loss with a depression score by multiple regression, accounting for other features of glaucoma.METHODS: One hundred and fifteen patients diagnosed with primary open-angle glaucoma completed the Beck Depression Inventory II questionnaire. The damage to their RGCs was assessed by high-definition optical coherence tomography (HD-OCT) and their function by pattern electroretinogram (PERG). On fifteen of these patients, 24-h salivary melatonin patterns were determined under light-controlled laboratory conditions, and analysis of eight clock related gene polymorphisms was performed.RESULTS: Backward stepwise multiple regression revealed that the BDI score was the strongest factor that was most closely associated with the HD-OCT-based percentage of global RGCs loss (standardized coefficient, b* = 0.784, p < 0.001), surpassing other related factors, including age, intraocular pressure, visual field loss, and PERG amplitude. A high BDI score was associated with the GNβ3 825C > T polymorphism (dbSNP rs5443).LIMITATIONS: This study did not specifically address damage to intrinsically photoreceptive RGCs. The gene study is based on a limited number of volunteers.CONCLUSIONS: Depression scores are strongly associated with RGCs loss, increasing abruptly above a threshold of 15 %, supporting the hypothesis that RGCs loss in advanced glaucoma may affect non-visual photic transduction and lead to mood disturbances.PMID:37084971 | DOI:10.1016/j.jad.2023.04.039

Transl Oncol. 2023 Apr 19;33:101672. doi: 10.1016/j.tranon.2023.101672. Online ahead of print.ABSTRACTBACKGROUND: The low 5-year survival rate of oral squamous cell carcinoma (OSCC) suggests that new prognostic indicators need to be identified to aid the clinical management of patients.METHODS: Saliva samples from OSCC patients and healthy controls were collected for proteomic and metabolomic sequencing. Gene expressed profiling was downloaded from TCGA and GEO databases. After the differential analysis, proteins with a significant impact on the prognosis of OSCC patients were screened. Correlation analysis was performed with metabolites and core proteins were identified. Cox regression analysis was utilized to stratify OSCC samples based on core proteins. The prognostic predictive ability of the core protein was then evaluated. Differences in infiltration of immune cells between the different strata were identified.RESULTS: There were 678 differentially expressed proteins (DEPs), 94 intersected DEPs among them by intersecting with differentially expressed genes in TCGA and GSE30784 dataset. Seven core proteins were identified that significantly affected OSCC patient survival and strongly correlated with differential metabolites (R2 > 0.8). The samples were divided into high- and low-risk groups according to median risk score. The risk score and core proteins were well prognostic factor in OSCC patients. Genes in high-risk group were enriched in Notch signaling pathway, epithelial mesenchymal transition (EMT), and angiogenesis. Core proteins were strongly associated with the immune status of OSCC patients.CONCLUSIONS: The results established a 7-protein signatures with the hope of early detection and the capacity for risk assessment of OSCC patient prognosis. Further providing more potential targets for the treatment of OSCC.PMID:37084685 | DOI:10.1016/j.tranon.2023.101672

Crit Rev Food Sci Nutr. 2023 Apr 19:1-29. doi: 10.1080/10408398.2023.2198605. Online ahead of print.ABSTRACTPersonalized nutrition (PN) has gained much attention as a tool for empowerment of consumers to promote changes in dietary behavior, optimizing health status and preventing diet related diseases. Generalized implementation of PN faces different obstacles, one of the most relevant being metabolic characterization of the individual. Although omics technologies allow for assessment the dynamics of metabolism with unprecedented detail, its translatability as affordable and simple PN protocols is still difficult due to the complexity of metabolic regulation and to different technical and economical constrains. In this work, we propose a conceptual framework that considers the dysregulation of a few overarching processes, namely Carbohydrate metabolism, lipid metabolism, inflammation, oxidative stress and microbiota-derived metabolites, as the basis of the onset of several non-communicable diseases. These processes can be assessed and characterized by specific sets of proteomic, metabolomic and genetic markers that minimize operational constrains and maximize the information obtained at the individual level. Current machine learning and data analysis methodologies allow the development of algorithms to integrate omics and genetic markers. Reduction of dimensionality of variables facilitates the implementation of omics and genetic information in digital tools. This framework is exemplified by presenting the EU-Funded project PREVENTOMICS as a use case.PMID:37077157 | DOI:10.1080/10408398.2023.2198605

Biol Sex Differ. 2023 Apr 19;14(1):21. doi: 10.1186/s13293-023-00507-w.ABSTRACTBACKGROUND: The polycystic ovary syndrome (PCOS) is associated with insulin resistance, obesity and cardiometabolic comorbidities. We here challenged the hypothesis, using state-of-the art proton nuclear magnetic resonance spectroscopy metabolomics profiling, that androgen excess in women induces also a certain masculinization of intermediate metabolism that is modulated by obesity.METHODS: Participants were 53 Caucasian young adults, including 17 women with classic PCOS consisting of hyperandrogenism and ovulatory dysfunction, 17 non-hyperandrogenic women presenting with regular menses, and 19 healthy men, selected in order to be similar in terms of age and body mass index (BMI). Half of the subjects had obesity defined by a body mass index ≥ 30 kg/m2. Subjects maintained the same diet unrestricted in carbohydrates for 3 days before sampling and maintained their lifestyle and exercise patterns prior and during the study. Plasma samples were submitted to proton nuclear magnetic resonance spectroscopy metabolomics profiling.RESULTS: Obesity associated a metabolomics profile mainly characterized by increased branched chain and aromatic aminoacids. Regardless of obesity, this unfavorable profile also characterized men as compared with control women, and was shared by women with PCOS. Notably, the negative impact of obesity on metabolomics profile was restricted to women, with obese men showing no further deterioration when compared with their non-obese counterparts.CONCLUSIONS: Serum metabolomics profiling by proton nuclear magnetic resonance spectroscopy reveals sexual dimorphism, and masculinization of intermediate metabolism in women with PCOS, further suggesting a role for sex and sex hormones in the regulation of intermediate metabolism.PMID:37076926 | DOI:10.1186/s13293-023-00507-w