PubMed

Kidney Med. 2024 Oct 16;6(12):100920. doi: 10.1016/j.xkme.2024.100920. eCollection 2024 Dec.ABSTRACTRATIONALE & OBJECTIVE: Diabetic kidney disease (DKD) is one of the leading causes of end-stage kidney disease globally. We aim to identify proteomic and metabolomic correlates of histologically confirmed DKD that may improve our understanding of its pathophysiology.STUDY DESIGN: A cross-sectional study.SETTING & PARTICIPANTS: A total of 434 Boston Kidney Biopsy Cohort participants.PREDICTORS: Histopathological diagnosis of DKD on biopsy.OUTCOMES: Proteins and metabolites associated with DKD.ANALYTICAL APPROACH: We performed linear regression to identify circulating proteins and metabolites associated with a histopathological diagnosis of DKD (n = 81) compared with normal or thin basement membrane (n = 27), and other kidney diseases without diabetes (n = 279). Pathway enrichment analysis was used to explore biological pathways enriched in DKD. Identified proteins were assessed for their discriminative ability in cases of DKD versus a distinct set of 48 patients with diabetes but other kidney diseases.RESULTS: After adjusting for age, sex, estimated glomerular filtration, and albuminuria levels, there were 8 proteins and 1 metabolite that differed between DKD and normal/thin basement membrane, and 84 proteins and 11 metabolites that differed between DKD and other kidney diseases without diabetes. Five proteins were significant in both comparisons: C-type mannose receptor 2, plexin-A1, plexin-D1, renin, and transmembrane glycoprotein NMB. The addition of these proteins improved discrimination over clinical variables alone of a histopathological diagnosis of DKD on biopsy among patients with diabetes (change in area under the curve 0.126; P = 0.008).LIMITATIONS: A cross-sectional approach and lack of an external validation cohort.CONCLUSIONS: Distinct proteins and biological pathways are correlated with a histopathological diagnosis of DKD.PMID:39634330 | PMC:PMC11615146 | DOI:10.1016/j.xkme.2024.100920

Front Endocrinol (Lausanne). 2024 Nov 20;15:1481014. doi: 10.3389/fendo.2024.1481014. eCollection 2024.ABSTRACTINTRODUCTION: Microplastics (MPs) are environmental pollutants that pose potential risks to living organisms. MPs have been shown to accumulate in human organs, including the placenta. In this study, we investigated the biochemical impact of 5 μm polystyrene microplastics (PS-MPs) on term placental chorionic villi explants, focusing on cytotoxicity, oxidative stress, metabolic changes, and the potential for MPs to cross the placental barrier.METHODS: Term placental chorionic explants were cultured for 24 hours with varying concentrations of PS-MPs, with MTT assays used to determine the appropriate concentration for further analysis. Cytotoxicity was assessed using the lactate dehydrogenase (LDH) release assay over a period of up to 72 hours. Reactive oxygen species formation and antioxidant activity were evaluated using biochemical assays. Metabolomic profiling was performed using proton nuclear magnetic resonance (1H NMR).RESULTS: Placental explants exposed to 100 μg/mL of PS-MPs showed a significant increase in cytotoxicity over time (p < 0.01). Levels of mitochondrial and total superoxide anion (p < 0.01 and p < 0.05, respectively) and hydrogen peroxide (p < 0.001) were significantly elevated. PS-MP exposure resulted in a reduction in total sulfhydryl content (p < 0.05) and the activities of antioxidant enzymes superoxide dismutase (p < 0.01) and catalase (p < 0.05), while glutathione peroxidase activity increased (p < 0.05), and the oxidized/reduced glutathione ratio decreased (p < 0.05). Markers of oxidative damage, such as malondialdehyde and carbonylated proteins, also increased significantly (p < 0.001 and p < 0.01, respectively), confirming oxidative stress. Metabolomic analysis revealed significant differences between control and PS-MP-exposed groups, with reduced levels of alanine, formate, glutaric acid, and maltotriose after PS-MP exposure.DISCUSSION: This study demonstrates that high concentrations of PS-MPs induce time-dependent cytotoxicity, oxidative stress, and alterations in the TCA cycle, as well as in folate, amino acid, and energy metabolism. These findings highlight the need for further research to clarify the full impact of MP contamination on pregnancy and its implications for future generations.PMID:39634179 | PMC:PMC11614646 | DOI:10.3389/fendo.2024.1481014

Front Aging. 2024 Nov 20;5:1494095. doi: 10.3389/fragi.2024.1494095. eCollection 2024.ABSTRACTINTRODUCTION: Aging is a complex process marked by a gradual decline in physiological function and increased susceptibility to diseases. Telomere length is frequently regarded as one of the primary biomarkers of aging. Metabolic profiles are key features in longevity and have been associated with both age and age-related diseases. We previously reported an increase in the telomere length in healthy female subjects when Ramadan fasting was combined with physical training. This study aims to characterize the metabolic signature differentiating the combined effects of exercise and fasting from exercise alone and explore the correlations with the previously reported telomere length changes.METHODS: Twenty-nine young, non-obese, and healthy female subjects were previously randomized into two groups: one group followed a 4-week exercise program, while the other group followed the same 4-week exercise program but also fasted during Ramadan. Metabolic profiles were assessed pre- and post-intervention using untargeted metabolomics.RESULTS AND DISCUSSION: Our results showed a significant decrease in many lipid metabolites in the exercise-while-fasting group, particularly ceramides. Our study sheds light on the dynamic changes in lipid metabolism and its potential role in inflammation and age-related diseases, and contributes to the broader understanding of how lifestyle factors can influence cellular aging and metabolic health.PMID:39633874 | PMC:PMC11615071 | DOI:10.3389/fragi.2024.1494095

Genome Med. 2024 Dec 4;16(1):144. doi: 10.1186/s13073-024-01415-3.ABSTRACTBACKGROUND: Clear cell renal cell carcinoma (ccRCC) tumours develop and progress via complex remodelling of the kidney epigenome, transcriptome, proteome and metabolome. Given the subsequent tumour and inter-patient heterogeneity, drug-based treatments report limited success, calling for multi-omics studies to extract regulatory relationships, and ultimately, to develop targeted therapies. Yet, methods for multi-omics integration to reveal mechanisms of phenotype regulation are lacking.METHODS: Here, we present SiRCle (Signature Regulatory Clustering), a method to integrate DNA methylation, RNA-seq and proteomics data at the gene level by following central dogma of biology, i.e. genetic information proceeds from DNA, to RNA, to protein. To identify regulatory clusters across the different omics layers, we group genes based on the layer where the gene's dysregulation first occurred. We combine the SiRCle clusters with a variational autoencoder (VAE) to reveal key features from omics' data for each SiRCle cluster and compare patient subpopulations in a ccRCC and a PanCan cohort.RESULTS: Applying SiRCle to a ccRCC cohort, we showed that glycolysis is upregulated by DNA hypomethylation, whilst mitochondrial enzymes and respiratory chain complexes are translationally suppressed. Additionally, we identify metabolic enzymes associated with survival along with the possible molecular driver behind the gene's perturbations. By using the VAE to integrate omics' data followed by statistical comparisons between tumour stages on the integrated space, we found a stage-dependent downregulation of proximal renal tubule genes, hinting at a loss of cellular identity in cancer cells. We also identified the regulatory layers responsible for their suppression. Lastly, we applied SiRCle to a PanCan cohort and found common signatures across ccRCC and PanCan in addition to the regulatory layer that defines tissue identity.CONCLUSIONS: Our results highlight SiRCle's ability to reveal mechanisms of phenotype regulation in cancer, both specifically in ccRCC and broadly in a PanCan context. SiRCle ranks genes according to biological features. https://github.com/ArianeMora/SiRCle_multiomics_integration .PMID:39633487 | DOI:10.1186/s13073-024-01415-3

Cardiovasc Diabetol. 2024 Dec 4;23(1):433. doi: 10.1186/s12933-024-02531-5.ABSTRACTBACKGROUND: Apolipoprotein (apo) C-III is involved in several processes that increase triglyceride levels, inflammation, and insulin resistance. Four of its proteoforms have been the focus of several studies and have shown differential associations with cardiovascular risk biomarkers, mostly lipids. However, there are other proteoforms of apoC-III that have not yet been investigated in detail. The aim of this study was to evaluate the associations of seven apoC-III proteoforms with a comprehensive set of biomarkers, including lipid metabolism, inflammation, and glucose homeostasis.METHODS: Seven apoC-III proteoforms (apoC-III0a, apoC-III0b, apoC-III1, apoC-III1d, apoC-III2, apoC-III2d, and apoC-III0f) were measured using a mass spectrometry immunoassay in 875 participants from the cross-sectional study of the Di@bet.es cohort. The complete lipoprotein profile was obtained via the Liposcale test, and the proton nuclear magnetic resonance (1H-NMR)-assessed glycoprotein signals were also obtained as biomarkers of inflammation.RESULTS: Three proteoform ratios (apoC-III2d, apoC-III2, and apoC-III0f normalized to apoC-III1) showed protective associations with most of the cardiovascular risk biomarkers in comparison with total apoC-III in linear regression models and were negatively associated with triglycerides (β=-0.173, p < 0.001; β=-0.297, p < 0.001; β=-0.223, p = 0.002), very low-density (VLDL) particle concentration (β=-0.133, p < 0.001; β=-0.265, p < 0.001; β=-0.203, p < 0.001), GlycA (β=-0.148, p < 0.001; β=-0.263, p < 0.001; β=-0.211, p < 0.001) and homeostatic model assessment of insulin resistance (HOMA-IR) (β=-0.096, p = 0.003; β=-0.199, p < 0.001; β=-0.114, p = 0.002). These associations were partly independent of total apoC-III concentrations. Participants with high levels of these proteoforms had a lower prevalence of cardiometabolic disorders, such as type 2 diabetes (p = 0.022), obesity (p = 0.001), and metabolic syndrome (p = 0.013).CONCLUSIONS: While apoC-III is positively associated with biomarkers of cardiometabolic risk, the proportions of three apoC-III proteoforms show opposite associations, independent of total apoC-III concentrations. Measuring not only apoC-III but also the proportions of apoC-III proteoforms can provide valuable information since individuals with similar levels of total apoC-III could display opposite lipid profiles depending on the proportion of apoC-III proteoforms.PMID:39633383 | DOI:10.1186/s12933-024-02531-5

BMC Cancer. 2024 Dec 4;24(1):1493. doi: 10.1186/s12885-024-13234-1.ABSTRACTBACKGROUND: Gut microbiome modulation is a promising strategy for enhancing the response to immune checkpoint blockade (ICB). Fecal microbiota transplant studies have shown positive signals of improved outcomes in both ICB-naïve and refractory melanoma patients; however, this strategy is challenging to scale. Diet is a key determinant of the gut microbiota, and we have previously shown that (a) habitual high dietary fiber intake is associated with an improved response to ICB and (b) fiber manipulation in mice impacts antitumor immunity. We recently demonstrated the feasibility of a controlled high-fiber dietary intervention (HFDI) conducted in melanoma survivors with excellent compliance and tolerance. Building on this, we are now conducting a phase II randomized trial of HFDI versus a healthy control diet in melanoma patients receiving ICB.METHODS: This is a randomized, double-blind, fully controlled feeding study that will enroll 45 melanoma patients starting standard-of-care (SOC) ICB in three settings: adjuvant, neoadjuvant, and unresectable. Patients are randomized 2:1 to the HFDI (target fiber 50 g/day from whole foods) or healthy control diet (target fiber 20 g/day) stratified by BMI and cohort. All meals are prepared by the MD Anderson Bionutrition Core and are isocaloric and macronutrient-controlled. The intervention includes a 1-week equilibration period and then up to 11 weeks of diet intervention. Longitudinal blood, stool and tumor tissue (if available) are collected throughout the trial and at 12 weeks post intervention.DISCUSSION: This DIET study is the first fully controlled feeding study among cancer patients who are actively receiving immunotherapy. The goal of the current study is to establish the effects of dietary intervention on the structure and function of the gut microbiome in patients with melanoma treated with SOC immunotherapies. The secondary endpoints include changes in systemic and tumor immunity, changes in the metabolic profile, quality of life, symptoms, disease response and immunotherapy toxicity.TRIAL REGISTRATION: This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT04645680. First posted 2020-11-27; last verified 2024-06.PMID:39633321 | DOI:10.1186/s12885-024-13234-1

BMC Pediatr. 2024 Dec 4;24(1):795. doi: 10.1186/s12887-024-05291-z.ABSTRACTOBJECTIVE: Methylmalonic acidemia (MMAs) is known as a severe, complex, and lethal disorder of methylmalonate and cobalamin. The patients with MMA may have developmental, neurological, and metabolic disorders such as liver disease. Here, we aim to evaluate 6 Iranian patients suspected to MMA disorder.STUDY DESIGN: We will provide genetic results, biochemical analysis and treatment for these patients. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and variant screening in probands by whole exome sequencing (WES) were performed.RESULTS: A total of six homozygous variants were identified, including five previously identified variants and one novel variant, in the two MMA-causing genes as follows: c.577G > C, c.290 + 69G > T, c.662T > A, c.290 + 69G > T of MMAB, and c.100dupA, c.394 C > T of MMACHC. Sanger sequencing confirmed the identified variants. Additionally, metabolomics data analysis reliably identified elevated C3 and MMA levels, as well as abnormalities in the amino acid profile, indicating the presence of pathogenic variants.CONCLUSIONS: Our findings expand the global spectrum of genotypes in MMA. While WES, combined with metabolomics and biochemical analysis, offers valuable insights for accurate diagnosis and subtyping of MMA, it is most beneficial in complex cases where clinical findings are unclear.PMID:39633313 | DOI:10.1186/s12887-024-05291-z

BMC Microbiol. 2024 Dec 5;24(1):519. doi: 10.1186/s12866-024-03667-w.ABSTRACTBACKGROUND: Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Dysbiosis of gut microbiota acts as a cause of Treg abnormalities. However, the intestinal metabolic impact of PNS with children remains poorly understood. This study aims to investigate the dynamic changes of gut microbiota and it's metabolism in children with PNS.METHODS: Fecal and peripheral blood samples were separately collected from patients with initial diagnosis of PNS (PNS_In group), recurrence of PNS (PNS_Re group), and healthy controls (HCs group). The fecal samples were subjected to the microbiome and metabolome by the multi-omics analysis. Additionally, the peripheral blood samples were collected and associated inflammatory indicators were determined.RESULTS: We found that in PNS_In group, lipopolysaccharide (LPS), pro-inflammatory interleukin (IL)-6, IL-17A, IL-23p19, and IL-1β were significantly increased compared with those in HCs group. However, these abnormalities were dramatically reversed in PNS_Re group treated with prednisone acetate. Moreover, the crucial Treg/Th17 axis in PNS inflammation was also proved to be discriminated between PNS and HCs. Gut microbial dysbiosis was identified in PNS_In and PNS_Re patients. At the genus level, compared to HCs group, the abundance of Faecalibacterium notably changed in PNS_In and PNS_Re groups, showing negatively correlated with inflammatory factors. Moreover, the fecal metabolome of PNS_In and PNS_Re remarkably altered with the major impacts in the metabolism of phenylalanine, ABC transporters, arginine and proline.CONCLUSION: The dynamic changes of gut microbiota and associated metabolites are closely correlated with initial period and recurrence of PNS in children via probably regulating inflammatory Th17/Treg axis, which may potentially provide novel targets for the control of the disease.CLINICAL TRIAL NUMBER: Not applicable.PMID:39633292 | DOI:10.1186/s12866-024-03667-w

Nature. 2024 Dec 4. doi: 10.1038/s41586-024-08434-5. Online ahead of print.NO ABSTRACTPMID:39633058 | DOI:10.1038/s41586-024-08434-5

Sci Rep. 2024 Dec 4;14(1):30242. doi: 10.1038/s41598-024-76212-4.ABSTRACTThe global rise of multidrug-resistant pathogens, particularly Methicillin-resistant Staphylococcus aureus (MRSA), has become a critical public health concern, necessitating the urgent discovery of new antimicrobial agents. Griseorhodin C, a hydroxyquinone compound isolated from Streptomyces, has demonstrated significant inhibitory effects against MRSA. In this study, we employed a comprehensive approach combining transcriptome and metabolome analyses to investigate the underlying antimicrobial mechanism of Griseorhodin C. Our findings reveal that Griseorhodin C interferes with multiple bacterial metabolic pathways, including those essential for the biosynthesis and metabolism of amino acids, purine metabolism and energy metabolism, ultimately leading to bacterial growth inhibition and cell death. Notably, Griseorhodin C showed superior inhibitory effects compared to the clinical standard, vancomycin, both in vivo and vitro. These results highlight the potential of Griseorhodin C as a promising candidate for the development of new therapeutic strategies aimed at combating MRSA infections. The study underscores the importance of exploring natural products as sources of novel antibiotics in the ongoing fight against antimicrobial resistance.PMID:39632874 | DOI:10.1038/s41598-024-76212-4

NPJ Biofilms Microbiomes. 2024 Dec 5;10(1):144. doi: 10.1038/s41522-024-00618-1.ABSTRACTSarcopenia is a major health challenge due to an aging population. Probiotics may improve muscle function through gut-muscle axis, but their efficacy and mechanisms in treating sarcopenia remain unclear. This study investigated the impact of Bifidobacterium animalis subsp. lactis Probio-M8 (Probio-M8) on old mice and sarcopenia patients. We analyzed 43 subjects, including gut microbiome, fecal metabolome, and serum metabolome, using a multi-omics approach to assess whether Probio-M8 can improve sarcopenia by modulating gut microbial metabolites. Probio-M8 significantly improved muscle function in aged mice and enhanced physical performance in sarcopenia patients. It reduced pathogenic gut species and increased beneficial metabolites such as indole-3-lactic acid, acetoacetic acid, and creatine. Mediating effect analyses revealed that Probio-M8 effectively reduced n-dodecanoyl-L-homoserine lactone level in gut concurrent with increased creatine circulation, to significantly enhance host physical properties. These findings provide new insights into probiotics as a potential treatment for sarcopenia by modulating gut microbiota metabolism.PMID:39632843 | DOI:10.1038/s41522-024-00618-1

J Agric Food Chem. 2024 Dec 5. doi: 10.1021/acs.jafc.4c06855. Online ahead of print.ABSTRACTPolycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder. This study investigated the mitigating effects of the Antrodia cinnamomea polysaccharide (ACP) on a letrozole-induced PCOS rat model. Results demonstrated that ACP reduced obesity and ameliorated dyslipidemia in PCOS rats. Moreover, ACP restored estrous cycle regularity, suppressed polycystic ovarian changes, and regulated serum levels of sex hormones, SOD, and MDA. Furthermore, ACP increased the α-diversity and modulated the abundance of phyla (Bacteroidetes, Firmicutes, and Verrucomicrobia) and genera (Lactobacillus, Helicobacter, Akkermansia, Oscillospira, Coprococcus, Roseburia, Blautia, and Allobaculum) in the gut microbiota. ACP also restored compromised intestinal barriers by upregulating the expression of ZO1, Occludin, Claudin1, and Claudin7 in the colon. ACP mitigated ovarian fibrosis by preventing activation of the NLRP3 inflammasome, decreasing the expression of fibrotic markers (TGF-β1, collagen-I, α-SMA, and CTGF), and regulating four ovarian fibrosis-associated metabolomics pathways. Generally, dietary ACP effectively ameliorated clinical symptoms and inhibited ovarian fibrosis in PCOS rats.PMID:39632724 | DOI:10.1021/acs.jafc.4c06855

Cancer Med. 2024 Dec;13(23):e70424. doi: 10.1002/cam4.70424.ABSTRACTBACKGROUND: Colorectal cancer (CRC) is one of the most common cancers. Various options are available for treatment, but prognosis is still poor in the more advanced stages. Current screening methods are not as accurate for distinguishing between benign and malignant growths, resulting in unnecessary invasive procedures. Recently a focus has been placed on identifying metabolites. Of these, taurine has frequently been detected, and this particular compound has a multifactorial role in human physiology.METHODS: We conducted a systematic review of studies up till November 2023. Searches were done in three databases- MEDLINE, CINAHL-Ebsco, and PubMed. Three independent reviewers filter titles, abstracts, and full-texts according to selection criteria. Ten studies (samples = 1714) were identified showing a differential level of taurine in CRC patient samples. Quality assessment accounted for the risk of bias of each study using the 'robvis' tool. Where meaningful comparisons could be made, meta-analyses were carried out using the 'R' program for precalculated effect sizes with 'metagen' in R. The 'meta' package was utilised for creation of forest plots.FINDINGS: Taurine was shown to significantly increase odds of CRC. It was also significantly associated with being a discriminator for CRC as a diagnostic metabolite. This was maintained at various stages of CRC. Taurine had increased expression in CRC patients, especially when the matrix utilised was blood. Nevertheless, there was significant heterogeneity for some outcomes.INTERPRETATION: In conclusion, these findings highlight the potential of using taurine as well as other bile acid metabolites (lithocholic and ursodeoxycholic acid) to diagnose CRC and illustrate the link with microbiome interactions. Overall increased taurine concentration are associated with significantly increased odds for CRC. There was mostly an increase in relative expression of taurine in CRC samples, excluding results from Wang et al.PMID:39632512 | DOI:10.1002/cam4.70424

Int J Food Sci Nutr. 2024 Dec 4:1-14. doi: 10.1080/09637486.2024.2437469. Online ahead of print.ABSTRACTPhosphatidylcholine (PC) has garnered considerable attention due to its involvement in a wide array of crucial biological functions. However, there is still much to active explore regarding the precise mechanisms that underlie PC's actions in the context of high-fat diet. In this study, we found that both PC intervention and treatment significantly mitigated lipid accumulation, liver damage, and body weight gaining triggered by the high-fat diet. Untargeted and targeted metabolomic analyses uncovered substantial effects of PC on bile acid metabolism, especially led to a substantial reduction in elevated levels of free bile acids. 16S rRNA gene sequencing revealed that PC modulated the gut microbiota structures and compositions in high-fat diet mice, particularly exhibiting a positive association with Pseudoflavonifractor abundance, and a negative correlation with Olsenella, Parasutterella, and Allobaculum abundance. Our study suggested that PC held promise as a potential candidate for alleviating lipid metabolism injury, liver disease or obesity.PMID:39632393 | DOI:10.1080/09637486.2024.2437469

Gut Microbes. 2024 Jan-Dec;16(1):2434675. doi: 10.1080/19490976.2024.2434675. Epub 2024 Dec 4.ABSTRACTAutism spectrum disorder (ASD) currently lacks effective diagnostic and therapeutic approaches. Disruptions in the gut ecosystem have been observed in individuals with ASD, suggesting that targeting gut microbiota through probiotic and dietary supplementation may serve as a potential treatment strategy. This two-phase study aimed to characterize the fecal metagenome of children with ASD and investigate the beneficial effects of a combined probiotic and medium-carbohydrate intervention in ASD. Fecal metagenomes of children with ASD were compared to those of typically developing children, revealing intestinal dysbiosis in ASD, characterized by reduced levels of Prevotella sp. Dialister invisus, and Bacteroides sp. along with increased predicted abundances of inosine, glutamate, xanthine, and methylxanthine. The gut bacteriome and phageome exhibited high cooperativity. In a 3-month pilot study, Bifidobacterium animalis subsp. lactis Probio-M8 (Probio-M8) was administered alongside a medium-carbohydrate diet to Chinese children with ASD. The primary endpoint was the Childhood Autism Rating Scale (CARS), while the secondary endpoint was the Gastrointestinal Symptom Rating Scale (GSRS). A total of 72 autistic children were initially recruited for the intervention study, but only 53 completed the intervention. Probio-M8, in combination with dietary intervention, significantly improved CARS and GSRS scores, increased fecal levels of Bifidobacterium animalis, Akkermansia muciniphila, Fusicatenibacter saccharivorans, and Sutterella sp. while also reducing Blautia obeum (Benjamini-Hochberg corrected p ≤ 0.05 for all cases). The intervention also modulated fecal metabolites associated with the metabolism of amino acids (lysine), neurotransmitters (glutamate, γ-aminobutyric acid), polyunsaturated fatty acids (arachidonate, myristic acid), and vitamin B3. In conclusion, Probio-M8 combined with medium-carbohydrate diet effectively improved ASD symptoms, with associated changes in the gut microbiome and metabolome, supporting its potential as an adjunctive therapy for ASD.PMID:39632378 | DOI:10.1080/19490976.2024.2434675

Ecotoxicol Environ Saf. 2024 Dec 3;289:117444. doi: 10.1016/j.ecoenv.2024.117444. Online ahead of print.ABSTRACTPerfluorooctanoic acid (PFOA) and tetrabromobisphenol A (TBBP-A) are emerging environmental contaminants with recognized potential health and ecological risks. This study investigated the effects of PFOA and TBBP-A exposure on the global of metabolites of silkworm gut with GC-MS metabolomics. Our results revealed distinct metabolic alterations in silkworms exposed to PFOA and TBBP-A, highlighting their differential impacts on silkworm health and productivity. Exposure to these chemicals significantly altered metabolic profiles, leading to disruptions in pathways related to lipid, carbohydrate, and amino acid metabolism. These findings suggest that PFOA and TBBP-A disrupt crucial metabolic processes in silkworms, indicating potential toxicity and prompting further investigation into their effects on human health and the environment. Ongoing research is crucial to develop safer alternatives and mitigate the risks associated with these persistent contaminants.PMID:39632329 | DOI:10.1016/j.ecoenv.2024.117444

New Phytol. 2024 Dec 4. doi: 10.1111/nph.20303. Online ahead of print.ABSTRACTThe plant community has a strong track record of RNA sequencing technology deployment, which combined with the recent advent of spatial platforms (e.g. 10× genomics) has resulted in an explosion of single-cell and nuclei datasets that can be positioned in an in situ context within tissues (e.g. a cell atlas). In the genomics era, application of proteomics technologies in the plant sciences has always trailed behind that of RNA sequencing technologies, largely due in part to upfront cost, ease-of-use, and access to expertise. Conversely, the use of early analytical tools for characterizing small molecules (metabolites) from plant systems predates nucleic acid sequencing and proteomics analysis, as the search for plant-based natural products has played a significant role in improving human health throughout history. As the plant sciences field now aims to fully define cell states, cell-specific regulatory networks, metabolic asymmetry and phenotypes, the measurement of proteins and metabolites at the single-cell level will be paramount. As a result of these efforts, the plant community will unlock exciting opportunities to accelerate discovery and drive toward meaningful translational outcomes.PMID:39632263 | DOI:10.1111/nph.20303

Food Chem. 2024 Nov 24:142224. doi: 10.1016/j.foodchem.2024.142224. Online ahead of print.ABSTRACTThis study explored the changes in nutrients, metabolites, and enzyme activity in Citrus reticulata peel powders (CRPP) under conventional or ultrasound-assisted solid-state fermentation (SSF) using Aspergillus niger CGMCC 3.6189. Compared to nonfermented CRPP (NF-CRPP), ultrasound-assisted fermented CRPP (UIS-CRPP) significantly increased total protein and carotenoid levels by 85.26 % and 179.68 %, respectively, surpassing conventionally-fermented CRPP (FO-CRPP). Among the 521 identified differential metabolites, organic acids, lipids, and flavonoids were predominant. Flavonoid accumulation was primarily driven by the flavone and flavonol biosynthesis pathway, with 90.47 % and 90.00 % of differential flavonoids upregulated in FO-CRPP and UIS-CRPP, respectively. SSF significantly increased phenylalanine, tyrosine, and methionine levels, and tyrosine ammonia-lyase and β-D-glucosidase activities, with higher levels in UIS-CRPP. These findings suggest that conventional and ultrasound-assisted fermentation enhances flavonoid levels in CRPP by modulating key enzyme activities in flavonoid biosynthesis and biotransformation. Our study offers a feasible approach for producing value-added products from citrus peel waste.PMID:39632168 | DOI:10.1016/j.foodchem.2024.142224

Ann Thorac Cardiovasc Surg. 2024;30(1). doi: 10.5761/atcs.oa.24-00126.ABSTRACTPURPOSE: Although the clinical outcomes of on-pump (ONCAB) and off-pump CABG (OPCAB) are well established, their metabolomic impacts remain underexplored. This study aims to compare the metabolic profiles of ONCAB and OPCAB to identify differential metabolites associated with clinical outcomes.METHODS: In a prospective cohort study conducted between January 2023 and September 2023, 100 plasma samples from 20 patients undergoing isolated elective CABG (10 per group) were analyzed. Samples were collected preoperatively and at multiple postoperative time points (Days 0-3) and processed using proton nuclear magnetic resonance (1H-NMR). Advanced statistical modeling was applied to identify differential metabolites.RESULTS: No significant differences were found in clinical outcomes, although ONCAB showed higher postoperative CKMB levels. Both procedures induced metabolomic alterations, with ONCAB demonstrating a more substantial impact, particularly on Day 0. Key metabolites, including leucine, succinate, creatine, glucose, and adenine, affected starch and sucrose metabolism.CONCLUSION: ONCAB induces more pronounced metabolic shifts immediately postsurgery, involving protein and energy turnover, oxidative stress, and disrupted glucose metabolism, indicative of cellular stress responses. A comprehensive understanding of these metabolic changes is critical for informing targeted interventions and supports the use of OPCAB as a preferred strategy for patients with elevated metabolic risks.PMID:39631940 | DOI:10.5761/atcs.oa.24-00126

Zhongguo Fei Ai Za Zhi. 2024 Oct 20;27(10):725-734. doi: 10.3779/j.issn.1009-3419.2024.106.28.ABSTRACTBACKGROUND: Metabolic change is one of the important characteristics of radiation pneumonitis. Radiotherapy, as a conventional method for the treatment of thoracic tumors, can not only effectively kill tumor cells, but also cause adverse reactions such as local inflammation and fibrosis, which leads to limited therapeutic effect and profound impact on the quality of life of patients. Therefore, it is of great significance to explore the metabolic changes caused by radiotherapy. The aim of this study was to investigate the effects of X-ray irradiation on the metabolism of a mouse lung epithelial cell line (murine lung epithelial-12, MLE12).METHODS: MLE12 cells were' cultured in vitro and randomly divided into radiation group (IR) and control group (NC). Cells in the IR group were irradiated at a dose of 10 Gy using a Hitachi X-ray irradiator. Cell supernatant samples were collected at 48 h after irradiation. Metabolomic analysis of the samples was performed by liquid chromatograph mass spectrometer (LC/MS).RESULTS: LC/MS metabolomics analysis revealed the metabolic changes of MLE12 cells at 48 h after irradiation. A total of 38 secretory metabolites were altered in the IR group compared with the NC group. According to the annotation of Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the differential metabolites are mainly involved in nucleotide metabolism, amino acid metabolism and lipid metabolism, among which the difference in nucleotide metabolism is the most significant.CONCLUSIONS: The metabolism of MLE12 cells was significantly affected by X-ray irradiation, mainly affecting the nucleotide metabolic pathways, including purine and pyrimidine metabolites and related metabolic pathways.PMID:39631829 | DOI:10.3779/j.issn.1009-3419.2024.106.28