PubMed

Integr Biol (Camb). 2023 Apr 10:zyad005. doi: 10.1093/intbio/zyad005. Online ahead of print.ABSTRACTOvarian cancer (OC) is the second most common cancer of the female reproductive system. Due to the asymptomatic nature of early stages of OC and an increasingly poor prognosis in later stages, methods of screening for OC are much desired. Furthermore, screening and diagnosis processes, in order to justify use on asymptomatic patients, must be convenient and non-invasive. Recent developments in machine-learning technologies have made this possible via techniques in the field of metabolomics. The objective of this research was to use existing metabolomics data on OC and various analytic methods to develop a machine-learning model for the classification of potentially OC-related metabolite biomarkers. Pathway analysis and metabolite-set enrichment analysis were performed on gathered metabolite sets. Quantitative molecular descriptors were then used with various machine-learning classifiers for the diagnostics of OC using related metabolites. We elucidated that the metabolites associated with OC used for machine-learning models are involved in five metabolic pathways linked to OC: Nicotinate and Nicotinamide Metabolism, Glycolysis/Gluconeogenesis, Aminoacyl-tRNA Biosynthesis, Valine, Leucine and Isoleucine Biosynthesis, and Alanine, Aspartate and Glutamate Metabolism. Several classification models for the identification of OC using related metabolites were created and their accuracies were confirmed through testing with 10-fold cross-validation. The most accurate model was able to achieve 85.29% accuracy. The elucidation of biological pathways specific to OC using metabolic data and the observation of changes in these pathways in patients have the potential to contribute to the development of screening techniques for OC. Our results demonstrate the possibility of development of the machine-learning models for OC diagnostics using metabolomics data.PMID:37032481 | DOI:10.1093/intbio/zyad005

Phytomedicine. 2023 Apr 3;114:154804. doi: 10.1016/j.phymed.2023.154804. Online ahead of print.ABSTRACTBACKGROUND: After being processed with different excipients, the clinical application of Coptidis Rhizoma (CR) is differentially investigated. However, the underlying mechanism and material basis are not clear, and there is a lack of attention to the collaborative working mode of herbal medicine during exploration.PURPOSE: To characterize the specific mechanism of wine/zingiberis rhizoma recens/euodiae fructus processed CR (wCR/zCR/eCR) and to investigate the role of excipients during processing.METHODS: The multi-organ metabolomics approach was employed to explore the target organs of wCR/zCR/eCR and multiple pathways being triggered in each organ. The tissue distribution of CR and wCR/zCR/eCR components was compared to indicate the material basis of efficacy change after processing. Further, the network pharmacology study coupled with experimental validation was conducted to support metabolomic research and predicted active ingredients and core targets, and the molecular docking coupled with binding test was performed to identify the binding between active ingredient and core target.RESULTS: The multi-organ metabolomics and network pharmacology study elucidated the intervening effect of wCR on heart/lung, zCR on stomach/colon, and eCR on liver/colon/stomach. Combined with molecular docking, binding test and tissue distribution studies, the specific mechanism was as follows: the wine made iso-quinoline alkaloids in CR more likely to accumulate in heart/lung, thus triggering the core targets of PTGS2, NOS2, ESR1 and SLC6A4 in heart/lung, and thereby highlighting the detoxifying and cardiopulmonary protective effect of wCR. The zingiberis rhizoma recens and euodiae fructus made organic acids in CR more likely to accumulate in stomach/colon and liver/colon/stomach respectively, thus triggering the core targets of ACTB, TNF and PRKCA in stomach/colon, the core targets of ACTB, TNF, PRKCA and GPT in stomach/colon/liver, and thereby highlighting the improving effect of zCR/eCR on digestive function.CONCLUSION: Iso-quinoline alkaloids were the material basis of CR for anti-inflammation, and organic acids were mainly responsible for regulating gastrointestinal function. Due to the influence of excipients on the accumulation tendency of CR components, the differentially highlighted application of wCR/zCR/eCR was achieved. These findings propose a novel strategy for processing mechanism research.PMID:37031638 | DOI:10.1016/j.phymed.2023.154804

J Psychiatr Res. 2023 Apr 4;161:426-434. doi: 10.1016/j.jpsychires.2023.03.032. Online ahead of print.ABSTRACTBACKGROUND: Post-stroke depression (PSD) is a common mental disorder of stroke survivors, its pathogenesis remains elusive. Previous studies suggested a role of the microbiota-gut-brain (MGB) axis in stroke and depression. In this study, we characterized microbial composition and function, and gut-brain metabolic signatures, in PSD rats. We aim to explore how disordered gut microbes participate in the pathogenesis of PSD through the MGB axis.MATERIALS AND METHODS: 16S rRNA gene sequence and fecal metabolome analysis were performed to identify the gut microbiome and their functional metabolites in PSD rats. Then, the lipid metabolic signatures in the prefrontal cortex (PFC) of PSD were conducted by liquid chromatography mass spectrometry. Finally, the potential pathway between gut and brain in the onset of PSD were explored.RESULTS: Compared to control and stroke rats, there were 10 genera (most of them belonged to phylum Firmicutes) significantly changed and 3 short chain fatty acids (SCFAs: butyric acid, acetic acid and pentanoic acid) significantly decreased in PSD rats. Meanwhile, altered gut microbial in PSD rats was significantly associated with these SCFAs. Compared with control and stroke rats, 57 lipid metabolites in the PFC of PSD rats were significantly changed. In addition, the altered SCFAs in PSD rats were also significantly correlated with most of disordered lipid metabolites in PFC.CONCLUSIONS: Our findings suggest that the SCFAs may be a bridge of gut-brain communication. The Firmicutes-SCFAs-lipid metabolism might be a potential pathway to further investigate the MGB axis and pathogenesis of PSD.PMID:37031497 | DOI:10.1016/j.jpsychires.2023.03.032

Cancer Med. 2023 Apr 9. doi: 10.1002/cam4.5857. Online ahead of print.ABSTRACTBACKGROUND: Despite aggressive treatment, more than 90% of glioblastoma (GBM) patients experience recurrences. GBM response to therapy is currently assessed by imaging techniques and tissue biopsy. However, difficulties with these methods may cause misinterpretation of treatment outcomes. Currently, no validated therapy response biomarkers are available for monitoring GBM progression. Metabolomics holds potential as a complementary tool to improve the interpretation of therapy responses to help in clinical interventions for GBM patients.METHODS: Saliva and blood from GBM patients were collected pre and postoperatively. Patients were stratified conforming their progression-free survival (PFS) into favourable or unfavourable clinical outcomes (>9 months or PFS ≤ 9 months, respectively). Analysis of saliva (whole-mouth and oral rinse) and plasma samples was conducted utilising LC-QqQ-MS and LC-QTOF-MS to determine the metabolomic and lipidomic profiles. The data were investigated using univariate and multivariate statistical analyses and graphical LASSO-based graphic network analyses.RESULTS: Altogether, 151 metabolites and 197 lipids were detected within all saliva and plasma samples. Among the patients with unfavourable outcomes, metabolites such as cyclic-AMP, 3-hydroxy-kynurenine, dihydroorotate, UDP and cis-aconitate were elevated, compared to patients with favourable outcomes during pre-and post-surgery. These metabolites showed to impact the pentose phosphate and Warburg effect pathways. The lipid profile of patients who experienced unfavourable outcomes revealed a higher heterogeneity in the abundance of lipids and fewer associations between markers in contrast to the favourable outcome group.CONCLUSION: Our findings indicate that changes in salivary and plasma metabolites in GBM patients can potentially be employed as less invasive prognostic biomarkers/biomarker panel but validation with larger cohorts is required.PMID:37031458 | DOI:10.1002/cam4.5857

Egypt J Immunol. 2023 Apr;30(2):83-98.ABSTRACTDiabetic retinopathy (DR) is a typical microvascular complication of diabetes mellitus (DM) and it remains one of the leading causes of vision loss worldwide. Studies postulated that a distinct metabolic signature of DR exists and can be resolved from that of diabetes alone. Serum Semaphorin3A (Sema3A) levels have also been found to be correlated with the phenotypes of diabetic retinopathy. We aimed to analyze and identify serum metabolites and serum Sema3A levels that could be useful biomarkers of DR progression. This cross-sectional study included 45 type 2 diabetes (T2D) patients. Diabetic patients were divided into three groups based on the status of their complications: non-DR (NDR, n=15), non-proliferative DR (NPDR, n=15), and proliferative DR (PDR, n=15) groups. Serum metabolomic profiles of these patients were determined by using high-performance liquid chromatography-mass spectrometry (HPLC-MS), and serum Sema3A levels measured by ELISA. Metabolomics analysis revealed a set of metabolites that were altered in the serum of PDR patients as compared with NPDR and NDR groups. Among these metabolites total asymmetric dimethylarginine (ADMA) and Kynurenine were potential predictors of PDR patients. Significantly higher serum levels of Sema3A in PDR patients as compared with NPDR and NDR groups (p < 0.001), their serum levels were positively correlated with the central macular thickness (r= 0.952, p < 0.001) and negatively correlated with the superficial macular density (r=-0.952, p < 0.001). In conclusion, the metabolite signatures identified in this study and serum Sema3A levels could be proposed as biomarkers for DR development and progression in T2D patients. However, Sema3A was superior to metabolomics in the prediction of the severity of DR.PMID:37031410

Clin Nutr. 2023 Apr 8;42(6):899-908. doi: 10.1016/j.clnu.2023.04.004. Online ahead of print.ABSTRACTBACKGROUND & AIM: For older adults, the dietary protein intake has shown to be skewed towards the evening meal. Resultingly, the vital source of essential amino acids could be insufficient after some meals, while after the evening meal the dietary protein could be suboptimally utilized for protein synthesis. The present study explored if an even distribution of the protein intake could improve the dietary amino acid absorption and whole-body protein net-balance.METHODS: Twenty-four healthy elderly males and females were included in a randomized controlled trial. Ten days of habituation to either an EVEN (n = 12) or SKEWED (n = 12) protein intake, was followed by a trial day. The total protein intake was controlled at 1.5 g/kg LBM, divided into 30% at each main meal in EVEN, and into 15% at breakfast and lunch and 60% at dinner in SKEWED. Snacks with 5% of the protein intake were served between meals. Energy intake in the meals and snacks were equal in both groups. Intrinsically labelled 2H5-phenylalanine minced meat was served as the dietary protein to assess the amino acid absorption. On the trial day, infusion of 2H8-phenylalanine and 2H2-tyrosine, and blood samples taken over 11 h were used to measure whole-body protein turnover. Vastus lateralis muscle biopsies were taken to measure 9 h muscle protein FSR.RESULTS: Amino acid absorption rates and concentrations were greater in EVEN compared to SKEWED protein intake. Whole-body protein breakdown rates were lower with similar protein synthesis rates, and consequently the net-balance was greater in EVEN after breakfast and lunch compared to SKEWED and were the same in both groups after dinner. Muscle protein FSR were not different between EVEN and SKEWED.CONCLUSIONS: The whole-body protein net-balance was more positive in EVEN compared to SKEWED for an extended time of the measured period, driven by a lower whole-body protein breakdown in EVEN.CLINICAL TRIALS REGISTRATION: NCT03870425, https://clinicaltrials.gov/ct2/show/NCT03870425.PMID:37086618 | DOI:10.1016/j.clnu.2023.04.004

Nat Commun. 2023 Apr 8;14(1):1979. doi: 10.1038/s41467-023-37712-5.ABSTRACTChanges in the transcriptional machinery cause aberrant self-renewal of non-stem hematopoietic progenitors. AF10 fusions, such as CALM-AF10, are generated via chromosomal translocations, causing malignant leukemia. In this study, we demonstrate that AF10 fusion proteins cause aberrant self-renewal via ENL, which binds to MOZ/MORF lysine acetyltransferases (KATs). The interaction of ENL with MOZ, via its YEATS domain, is critical for CALM-AF10-mediated leukemic transformation. The MOZ/ENL complex recruits DOT1L/AF10 fusion complexes and maintains their chromatin retention via KAT activity. Therefore, inhibitors of MOZ/MORF KATs directly suppress the functions of AF10 fusion proteins, thereby exhibiting strong antitumor effects on AF10 translocation-induced leukemia. Combinatorial inhibition of MOZ/MORF and DOT1L cooperatively induces differentiation of CALM-AF10-leukemia cells. These results reveal roles for the MOZ/ENL complex as an essential recruiting factor of the AF10 fusion/DOT1L complex, providing a rationale for using MOZ/MORF KAT inhibitors in AF10 translocation-induced leukemia.PMID:37031220 | DOI:10.1038/s41467-023-37712-5

Int J Infect Dis. 2023 Apr 6:S1201-9712(23)00135-2. doi: 10.1016/j.ijid.2023.04.003. Online ahead of print.ABSTRACTBACKGROUND: The clinical burden of influenza is increasing globally. Aging, immunosuppression, and underlying respiratory illness are determinants of poor clinical outcomes, including greater mortality. Bacterial infections seem to be the main reason. Updated information on the role of bacterial infection as the cause of complications would be of value in improving the prognosis of influenza patients.METHODS: A systematic review and meta-analysis were performed by using the Pubmed repository using keywords like: Influenza, H1N1, Streptococcus pneumoniae, bacterial coinfection, secondary coinfection, bacterial complications in pneumonia, and seasonal influenza. Only articles written in English were only included on publications from 2010 to 2020. Analyses were conducted following PRISMA guidelines. The results were independently validated using a TrinetX database cohort of roughly 4 million patients.RESULTS: We included 136 studies that contained data from 48,259 influenza-hospitalized patients of any age. Bacterial infections were diagnosed in 5,391 (11.2%). Streptococcus pneumoniae (30.7%) and Staphylococcus aureus (30.4%) were the most frequent microorganisms, followed by Haemophilus influenzae (7.1%) and Pseudomonas aeruginosa (5.9%). The random effects model of the meta-analysis indicated that bacterial infections posed a 3.4-fold increased risk of death compared to influenza infection alone. Unexpectedly, asthma was protective (odds ratio 0.8).CONCLUSION: Bacterial infections diagnosed in 11.2% of influenza patients increase 3.4-fold the mortality risk. S. pneumoniae, S. aureus, H. influenzae and P. aeruginosa account for nearly 75% of cases. Earlier diagnosis and use of antibiotics should improve outcomes in this population.PMID:37030656 | DOI:10.1016/j.ijid.2023.04.003

Behav Brain Res. 2023 Apr 6:114423. doi: 10.1016/j.bbr.2023.114423. Online ahead of print.ABSTRACTPersicaria minor (P. minor) is a herbal plant with many uses in food, perfume, and the medical industry. P. minor extract contains flavonoids with antioxidant and anticholinesterase capacity, which could enhance cognitive functions. P. minor extract has been proven to enhance memory. However, its role in an animal model of chronic cerebral hypoperfusion (CCH), which resembles human vascular dementia, has yet to be explored. Therefore, the present study investigates the effects of chronic (14 days) administration of aqueous P. minor extract on different stages of learning and memory processes and the metabolic pathways involved in the chronic cerebral hypoperfused rats induced by the permanent bilateral occlusion of common carotid arteries (PBOCCA) surgery. Chronic treatment of P. minor extract at doses of 200 and 300mg/kg, enhanced recognition memory of the PBOCCA rats. P. minor extract (200mg/kg) was also found to restore the spatial memory impairment induced by CCH. A high dose (300mg/kg) of the P. minor extract significantly increased the expression of both ACh and GABA neurotransmitters in the hippocampus. Further, distinctive metabolite profiles were observed in rats with different treatments. Three major pathways involved in the cognitive enhancement mechanism of P. minor were identified. The present findings demonstrated an improving effect of P. minor extract on memory in the CCH rat model, suggesting that P. minor extract could be a potential treatment for vascular dementia and Alzheimer's patients. P. minor is believed to improve cognitive deficits by regulating pathways involved in retinol, histidine, pentose, glucuronate, and CoA metabolism.PMID:37030545 | DOI:10.1016/j.bbr.2023.114423

Biochim Biophys Acta Mol Basis Dis. 2023 Apr 6:166709. doi: 10.1016/j.bbadis.2023.166709. Online ahead of print.ABSTRACTMetabolic syndrome (MetS), characterized by a set of conditions that include obesity, hypertension, and dyslipidemia, is associated with increased cardiovascular risk. Exercise training (EX) has been reported to improve MetS management, although the underlying metabolic adaptations that drive its benefits remain poorly understood. This work aims to characterize the molecular changes induced by EX in skeletal muscle in MetS, focusing on gastrocnemius metabolic remodelling. 1H NMR metabolomics and molecular assays were employed to assess the metabolic profile of skeletal muscle tissue from lean male ZSF1 rats (CTL), obese sedentary male ZSF1 rats (MetS-SED), and obese male ZF1 rats submitted to 4 weeks of treadmill EX (5 days/week, 60 min/day, 15 m/min) (MetS-EX). EX did not counteract the significant increase of body weight and circulating lipid profile, but had an anti-inflammatory effect and improved exercise capacity. The decreased gastrocnemius mass observed in MetS was paralleled with glycogen degradation into small glucose oligosaccharides, with the release of glucose-1-phosphate, and an increase in glucose-6-phosphate and glucose levels. Moreover, sedentary MetS animals' muscle exhibited lower AMPK expression levels and higher amino acids' metabolism such as glutamine and glutamate, compared to lean animals. In contrast, the EX group showed changes suggesting an increase in fatty acid oxidation and oxidative phosphorylation. Additionally, EX mitigated MetS-induced fiber atrophy and fibrosis in the gastrocnemius muscle. EX had a positive effect on gastrocnemius metabolism by enhancing oxidative metabolism and, consequently, reducing susceptibility to fatigue. These findings reinforce the importance of prescribing EX programs to patients with MetS.PMID:37030522 | DOI:10.1016/j.bbadis.2023.166709

Sci Total Environ. 2023 Apr 6:163162. doi: 10.1016/j.scitotenv.2023.163162. Online ahead of print.ABSTRACTCoastal blue carbon ecosystems (BCE) support nearshore food webs and provide habitat for many commercially important fish and crustacean species. However, the complex links between catchment vegetation and the carbon food-base of estuarine systems are difficult to disern. We employed a multi-biomarker approach (stable isotope ratios - δ13C and δ15N, fatty acid trophic markers - FATMs and metabolomics - central carbon metabolism metabolites) to test links between estuarine vegetation and the food sources available to commercially important crabs and fish occurring within the river systems of the near-pristine eastern coastline of the Gulf of Carpentaria, Australia. Stable isotope analysis confirmed the dietary importance of fringing macrophytes to consumer diet, but showed that this is modulated by their dominance along the riverbank. FATMs indicative of specific food sources further confirmed the differences among upper intertidal macrophytes (driven by concentrations of 16: 1ω7, 18:1ω9, 18:2ω6, 18:3ω3 & 22.0) and seagrass (driven by 18:2ω6, 18:3ω3). These dietary patterns were also reflected in the concentration of central carbon metabolism metabolites. Overall, our study demonstrates the congruence of different biomarker approaches to resolve biochemical links between blue carbon ecosystems and important nekton species, and provides fresh insights into the pristine tropical estuaries of northern Australia.PMID:37030372 | DOI:10.1016/j.scitotenv.2023.163162

Int J Food Microbiol. 2023 Mar 30;395:110190. doi: 10.1016/j.ijfoodmicro.2023.110190. Online ahead of print.ABSTRACTThis study evaluated the potential of fermented garlic as a marinated lamb sauce ingredient to improve the quality and shelf life of chilled lamb. Garlic was subjected to Lacto-fermentation for 72 h at 37 °C using Lacticaseibacillus casei. The 1H NMR metabolomics profile showed the presence of eight amino acids and five organic acids in fermented garlic, indicating the attribution to the antioxidant and antimicrobial activities. The FRAP and DPPH assays of fermented garlic revealed antioxidant activities of 0.45 ± 0.09 mmol/100 g DW and 93.85 ± 0.02 %, respectively. Meanwhile, fermented garlic inhibited the growth of Escherichia coli (95 %), Staphylococcus aureus (99 %) and Salmonella Typhimurium (98 %). When fermented garlic was added to the marinade sauce, it successfully reduced the microbial load of lamb meat by 0.5 log CFU/g after 3 days of storage. There were no significant differences in color between the control and marinated lamb after 3 days of marinating in a sauce formulated with fermented garlic. Furthermore, marinated lamb significantly improved water-holding capacity, texture, juiciness, and overall acceptance. These findings indicated a potential addition of fermented garlic in marinade lamb sauce recipes to improve the quality and safety of meat products.PMID:37030193 | DOI:10.1016/j.ijfoodmicro.2023.110190

Theriogenology. 2023 Apr 1;204:8-17. doi: 10.1016/j.theriogenology.2023.03.023. Online ahead of print.ABSTRACTIn ram sperm, metabolites are important components of the plasma membrane, energy metabolism cycle, and precursors for other membrane lipids, and they may have important roles in maintaining plasma membrane integrity, energy metabolism, and regulation of cryotolerance. In this study, the ejaculates from 6 Dorper rams were pooled and sperm were systematically investigated by metabolomics at various steps of cryopreservation (37 °C, fresh [F]; from 37 to 4 °C, cooling [C]; and from 4 to -196 to 37 °C, frozen-thawed [FT]) to identify differential metabolites (DM). There were 310 metabolites identified, of which 86 were considered DMs. Regarding the DMs, there were 23 (0 up and 23 down), 25 (12 up and 13 down), and 38 (7 up and 31 down) identified during cooling (C vs F), freezing (FT vs C), and cryopreservation (FT vs F), respectively. Furthermore, some key polyunsaturated fatty acids (FAs), particularly, linoleic acid (LA), docosahexaenoic acid (DHA), and arachidonic acid (AA) were down-regulated during cooling and cryopreservation. Significant DMs were enriched in several metabolic pathways including biosynthesis of unsaturated FAs, LA metabolism, mammalian target of rapamycin (mTOR), forkhead box transcription factors (FoxO), adenosine monophosphate-activated protein kinase (AMPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K-Akt) signaling pathways, regulation of lipolysis in adipocytes, and FA biosynthesis. This was apparently the first report to compare metabolomics profiles of ram sperm during cryopreservation and provided new knowledge to improve this process.PMID:37030173 | DOI:10.1016/j.theriogenology.2023.03.023

Microbiol Res. 2023 Apr 6;272:127382. doi: 10.1016/j.micres.2023.127382. Online ahead of print.ABSTRACTIndoleamine 2,3-dioxygenase (Ido) is a tryptophan-degrading enzyme that is widely distributed across species. Ido catalyzes the first step of tryptophan (TRP) degradation and drives the de novo synthesis of nicotinamide adenine dinucleotide (NAD+) coenzymes via the kynurenine (KYN) pathway. The budding yeast Saccharomyces cerevisiae possesses a single IDO gene (BNA2) that is responsible for NAD+ synthesis, whereas a number of fungal species contain multiple IDO genes. However, the biological roles of IDO paralogs in plant pathogens remain unclear. In the current study, we identified three FgIDOs from the wheat head blight fungus Fusarium graminearum. FgIDOA/B/C expression was significantly induced upon TRP treatment. Targeted disruption of FgIDOA and/or FgIDOB caused different levels of NAD+ auxotrophy, thus resulting in pleotropic phenotypic defects. Loss of FgIDOA resulted in abnormal conidial morphology, reduced mycelial growth, decreased virulence in wheat heads and reduced deoxynivalenol accumulation. Exogenous addition of KYN or various intermediates involved in the KYN pathway rescued auxotrophy of the mutants. Metabolomics analysis revealed shifts toward alternative TRP degradation pathways to melatonin and indole derivatives in mutants lacking FgIDOB. Upregulation of partner genes in auxotrophic mutants and the capacity to rescue the auxotroph by overexpressing a partner gene indicated functional complementation among FgIDOA/B/C. Taken together, the results of this study provide insights into differential roles in paralogous FgIDOs and how fungal TRP catabolism modulates fungal development and virulence.PMID:37030080 | DOI:10.1016/j.micres.2023.127382

Ecotoxicol Environ Saf. 2023 Apr 6;256:114871. doi: 10.1016/j.ecoenv.2023.114871. Online ahead of print.ABSTRACTMicroplastics (MPs) pose one of the major environmental threats to marine organisms and ecosystems on a global scale. Although many marine crustaceans are highly susceptible to MPs pollution, the toxicological effects and mechanisms of MPs on crustaceans are poorly understood. The current study focused on the impacts of MPs accumulation in shrimp Litopenaeus vannamei at the behavioral, histological and biochemical levels. The results demonstrated the accumulation of polystyrene MPs in various organs of L. vannamei, with highest MPs abundance in the hepatopancreas. The MPs accumulated in shrimp caused growth inhibition, abnormal swimming behavior and reduced swimming performance of L. vannamei. Following MPs exposure, oxidative stress and lipid peroxidation were also observed, which were strongly linked to attenuated swimming activity of L. vannamei. The above MPs-induced disruption in balance of antioxidant system triggered the hepatopancreatic damage in L. vannamei, which was exacerbated with increasing MPs concentrations (from 0.02 to 1 mg L-1). Furthermore, metabolomics revealed that MPs exposure resulted in alterations of metabolic profiles and disturbed glycolysis, lipolysis and amino acid metabolism pathways in hepatopancreas of L. vannamei. This work confirms and expands the knowledge on the sublethal impacts and toxic modes of action of MPs in L. vannamei.PMID:37030048 | DOI:10.1016/j.ecoenv.2023.114871

J Pharm Biomed Anal. 2023 Mar 29;229:115375. doi: 10.1016/j.jpba.2023.115375. Online ahead of print.ABSTRACTTetrastigma hemsleyanum Diels et Gilg (TH) is one of the new eight Genuine Medicinal Materials of Zhejiang. It has extensive biological activities, such as anti-inflammatory, anti-tumor and analgesic activities, etc. In this study, the chemical components of TH were systematically investigated by ultra high-performance liquid chromatography-tandem quadrupole time of flight mass spectrometry (UPLC/Q-TOF-MS). Based on the MS spectrum, 39 compounds in TH extracts including 14 flavonoids, 10 fatty acids, 5 polyphenols and phenolic acids, 4 terpenes and other compounds were detected and tentatively identified. TH samples were treated under different drying methods (vacuum freeze drying, hot air drying, natural drying, light drying and vacuum drying). Besides, the effect of different drying methods on the content of 10 main chemical constituents in TH extracts including catechin, rutin, kaempferol-3-O-rutinoside and so on was also investigated by targeting metabolomics method with ultra high-performance liquid chromatography-tandem triple quadrupole mass spectrometry (UPLC-MS/MS) assisted by multivariate statistical analysis. Large differences were observed between vacuum drying and vacuum freeze drying with remarkable content changes. The contents of rutin, proanthocyanidin B1 and catechin were the most different among the various drying methods. The systematic identification of chemical constituents is helpful for the further medicinal development and application of TH. The effects of drying methods on the content of TH components were studied, which provided experimental data for the processing, storage and quality control of TH.PMID:37030030 | DOI:10.1016/j.jpba.2023.115375

Transfusion. 2023 Apr 8. doi: 10.1111/trf.17345. Online ahead of print.ABSTRACTBACKGROUND: The risk of military and civilian radiation exposure is increasing, and determining the effects of exposure is a high priority. Irradiation of the nearby blood supply after a nuclear event may impede mobilization of blood products for resuscitation at a time of great need. RBCs are administered to patients with trauma and hemorrhage to transport and deliver oxygen and avoid tissue hypoxia. Here we determine the effects of ionizing radiation on the energy metabolome of RBCs isolated from cold stored whole blood to determine if their stability is compromised by radiation exposure.STUDY DESIGN AND METHODS: Whole blood from healthy volunteers was subjected to 0, 25, or 75 Gy of X-irradiation, and stored at 4°C. RBCs were isolated from stored WB at 0, 1, 7, 14, and 21 days of storage. The levels of extracted Krebs cycle intermediates, nicotinamide adenine dinucleotides, and phosphorylated derivatives of adenosine and guanosine were determined by tandem mass spectroscopy.RESULTS: Irradiation at either 25Gy or 75Gy had no significant effect on any parameter measured compared to control (0Gy). However, there was a significant change over time in storage for ATP, GDP, and guanosine.DISCUSSION: Irradiation at doses up to 75Gy had no effect on the energy metabolome of RBCs prepared from blood stored at 4°C for up to 21 days, suggesting that the RBC energy metabolome is not affected by radiation exposure and the blood can still be used for resuscitation in trauma patients.PMID:37029665 | DOI:10.1111/trf.17345

J Vis Exp. 2023 Apr 7;(194). doi: 10.3791/65071.ABSTRACTHyperlipidemia has become a leading risk factor for cardiovascular diseases and liver injury worldwide. Fructus Phyllanthi (FP) is an effective drug against hyperlipidemia in Traditional Chinese Medicine (TCM) and Indian Medicine theories, however the potential mechanism requires further exploration. The present research aims to reveal the mechanism of FP against hyperlipidemia based on an integrated strategy combining network pharmacology prediction with metabolomics validation. A high-fat diet (HFD)-induced mice model was established by evaluating the plasma lipid levels, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Network pharmacology was applied to find out the active ingredients of FP and potential targets against hyperlipidemia. Metabolomics of plasma and liver were performed to identify differential metabolites and their corresponding pathways among the normal group, model group, and intervention group. The relationship between network pharmacology and metabolomics was further constructed to obtain a comprehensive view of the process of FP against hyperlipidemia. The obtained key target proteins were verified by molecular docking. These results reflected that FP improved the plasma lipid levels and liver injury of hyperlipidemia induced by a HFD. Gallic acid, quercetin, and beta-sitosterol in FP were demonstrated as the key active compounds. A total of 16 and six potential differential metabolites in plasma and liver, respectively, were found to be involved in the therapeutic effects of FP against hyperlipidemia by metabolomics. Further, integration analysis indicated that the intervention effects were associated with CYP1A1, AChE, and MGAM, as well as the adjustment of L-kynurenine, corticosterone, acetylcholine, and raffinose, mainly involving tryptophan metabolism pathway. Molecular docking ensured that the above ingredients acting on hyperlipidemia-related protein targets played a key role in lowering lipids. In summary, this research provided a new possibility for preventing and treating hyperlipidemia.PMID:37092814 | DOI:10.3791/65071

Cardiovasc Diabetol. 2023 Apr 7;22(1):82. doi: 10.1186/s12933-023-01815-6.ABSTRACTBACKGROUND: A new definition of metabolically healthy obesity (MHO) has recently been proposed to stratify the heterogeneous mortality risk of obesity. Metabolomic profiling provides clues to metabolic alterations beyond clinical definition. We aimed to evaluate the association between MHO and cardiovascular events and assess its metabolomic pattern.METHODS: This prospective study included Europeans from two population-based studies, the FLEMENGHO and the Hortega study. A total of 2339 participants with follow-up were analyzed, including 2218 with metabolomic profiling. Metabolic health was developed from the third National Health and Nutrition Examination Survey and the UK biobank cohorts and defined as systolic blood pressure < 130 mmHg, no antihypertensive drugs, waist-to-hip ratio < 0.95 for women or 1.03 for men, and the absence of diabetes. BMI categories included normal weight, overweight, and obesity (BMI < 25, 25-30, ≥ 30 kg/m2). Participants were classified into six subgroups according to BMI category and metabolic healthy status. Outcomes were fatal and nonfatal composited cardiovascular events.RESULTS: Of 2339 participants, the mean age was 51 years, 1161 (49.6%) were women, 434 (18.6%) had obesity, 117 (5.0%) were classified as MHO, and both cohorts had similar characteristics. Over a median of 9.2-year (3.7-13.0) follow-up, 245 cardiovascular events occurred. Compared to those with metabolically healthy normal weight, individuals with metabolic unhealthy status had a higher risk of cardiovascular events, regardless of BMI category (adjusted HR: 3.30 [95% CI: 1.73-6.28] for normal weight, 2.50 [95% CI: 1.34-4.66] for overweight, and 3.42 [95% CI: 1.81-6.44] for obesity), whereas those with MHO were not at increased risk of cardiovascular events (HR: 1.11 [95% CI: 0.36-3.45]). Factor analysis identified a metabolomic factor mainly associated with glucose regulation, which was associated with cardiovascular events (HR: 1.22 [95% CI: 1.10-1.36]). Individuals with MHO tended to present a higher metabolomic factor score than those with metabolically healthy normal weight (0.175 vs. -0.057, P = 0.019), and the score was comparable to metabolically unhealthy obesity (0.175 vs. -0.080, P = 0.91).CONCLUSIONS: Individuals with MHO may not present higher short-term cardiovascular risk but tend to have a metabolomic pattern associated with higher cardiovascular risk, emphasizing a need for early intervention.PMID:37029406 | DOI:10.1186/s12933-023-01815-6

World J Microbiol Biotechnol. 2023 Apr 8;39(6):151. doi: 10.1007/s11274-023-03603-6.ABSTRACTPesticide pollution in recent times has emerged as a grave environmental problem contaminating both aquatic and terrestrial ecosystems owing to their widespread use. Bioremediation using gene editing and system biology could be developed as an eco-friendly and proficient tool to remediate pesticide-contaminated sites due to its advantages and greater public acceptance over the physical and chemical methods. However, it is indispensable to understand the different aspects associated with microbial metabolism and their physiology for efficient pesticide remediation. Therefore, this review paper analyses the different gene editing tools and multi-omics methods in microbes to produce relevant evidence regarding genes, proteins and metabolites associated with pesticide remediation and the approaches to contend against pesticide-induced stress. We systematically discussed and analyzed the recent reports (2015-2022) on multi-omics methods for pesticide degradation to elucidate the mechanisms and the recent advances associated with the behaviour of microbes under diverse environmental conditions. This study envisages that CRISPR-Cas, ZFN and TALEN as gene editing tools utilizing Pseudomonas, Escherichia coli and Achromobacter sp. can be employed for remediation of chlorpyrifos, parathion-methyl, carbaryl, triphenyltin and triazophos by creating gRNA for expressing specific genes for the bioremediation. Similarly, systems biology accompanying multi-omics tactics revealed that microbial strains from Paenibacillus, Pseudomonas putida, Burkholderia cenocepacia, Rhodococcus sp. and Pencillium oxalicum are capable of degrading deltamethrin, p-nitrophenol, chlorimuron-ethyl and nicosulfuron. This review lends notable insights into the research gaps and provides potential solutions for pesticide remediation by using different microbe-assisted technologies. The inferences drawn from the current study will help researchers, ecologists, and decision-makers gain comprehensive knowledge of value and application of systems biology and gene editing in bioremediation assessments.PMID:37029313 | DOI:10.1007/s11274-023-03603-6